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This is a single arm, open-label, non-randomized, dose-escalation, phase I study to determine  the safety and efficacy of ssCART-19 in the treatment of patients with CD19 positive relapsed  or refractory acute lymphoblastic leukemia. This is a single arm, open-label, non-randomized, dose-escalation, phase I study to determine  the safety and efficacy of ssCART-19 in the treatment of patients with CD19 positive relapsed  or refractory acute lymphoblastic leukemia.  Primary objectives:  Determine the safety and tolerability of ssCART-19 cells in patients with refractory or  relapsed acute lymphoblastic leukemia.  Secondary objectives:  1. Observe the anti-tumor response of ssCART-19 cells to refractory or relapsed acute  lymphoblastic leukemia.  -  Overall remission rate (ORR) assessment during the 3 months after ssCART-19  administration，ORR includes CR and CRi  -  Duration of response (DOR)  -  Progression-free survival (PFS)  -  Overall survival (OS)  2. To characterize the in vivo cellular pharmacokinetic (PK) profile of ssCART-19 cells.  3. To characterize the pharmacodynamic (PD) profile of ssCART-19 cells. Inclusion Criteria:  1. Relapsed or refractory acute lymphoblastic leukemia (ALL):(1)Any Relaps after first  remission OR (2)Any BM relapse after allogeneic SCT and must be ≥ 3 months from SCT at  the time of ssCART-19 infusion OR (3)failed to reach CR after 2 cycles of induction  chemotherapy regimen OR (4)Patients with Ph+ ALL are eligible if they are intolerant  to or have failed two lines of TKI therapy, or if TKI therapy is contraindicated  2. CD19 tumor expression demonstrated in bone marrow or peripheral blood by flow  cytometry  3. Bone marrow with ≥ 5% lymphoblasts by morphologic assessment  4. Adequate organ function defined as:(1)left ventricular ejection fraction ≥ 50% by  echocardiogram；(2)creatinine ≤ 1.6mg/dl；(3)ALT and AST≤3 times the ULN for age, total  bilirubin ≤ 2.0mg/dl；(4)Must have a minimum level of pulmonary reserve defined as ≤  Grade 1 dyspnea and pulse oxygenation > 91% on room air  5. Informed consent is signed by the subject  6. Age 18 to 65  7. Fertility of men, to ensure that sexual partners can effectively contraception; Women  with fertility use effective contraceptive measures and agree to use contraceptive  measures throughout the study period  8. Qualified T cell amplification  9. Eastern cooperative oncology group (ECOG) performance status of 0 to 1  10. Vascular conditions for apheresis  11. The estimated survival time is more than 3 months Exclusion Criteria:  1. Isolated extra-medullary disease relapse  2. Combined with other malignant tumors  3. Has had treatment with any prior anti-CD19/anti-CD3 therapy, or any other antiCD19  therapy  4. Has had immunosuppressants or hormones within 2 weeks before signing informed consent,  or plan to use immunosuppressants or hormones after signing informed consent  5. Patients complying with any of hepatitis B surface antigen (HBsAg) and/or hepatitis B  e antigen (HBeAg) positive, hepatitis B e antibody (HBe-Ab) and/or hepatitis B core  antibody (HBc-Ab) positive and HBV-DNA copies being more than the lower limit of  detection, hepatitis C antibody (HCV-Ab) positive, anti-treponemia pallidum antibody  (TP-Ab) positive, EBV-DNA, and CMV-DNA copies being more than the lower limit of  detection  6. Has uncontrolled bacteria, fungi, viruses, mycoplasma or other types of infections  7. Infected with HIV, syphilis or COVID-19  8. Has a history of severe immediate hypersensitivity to aminoglycosides  9. Has past or present CNS diseases, such as epilepsy, cerebrovascular  ischemia/hemorrhage, dementia, cerebellar diseases or any CNS-related autoimmune  diseases  10. Has undergone cardiac angioplasty or stent implantation within 12 months before  signing informed consent, or having a history of myocardial infarction, unstable  angina pectoris or other clinically significant heart diseases  11. With primary immunodeficiency  12. Has had severe immediate hypersensitivity reaction to any drug to be used in this  study  13. Has had treat with live vaccine within 6 weeks prior to screening  14. Pregnant or lactating women  15. Has active autoimmune diseases  16. Has active acute or chronic graft-versus-host disease (GVHD) before signing informed  consent  17. Patient has an investigational medicinal product within 3 months before signing  informed consent  18. Patients with other conditions making the patients unsuitable for receiving cell  therapy as judged by the investigator

The purpose of the You + ME Registry and Biobank is to collect clinical and patient-reported  data and biological samples (e.g. blood) from people living with Myalgic Encephalomyelitis  (also known as chronic fatigue syndrome or ME/CFS), people with long-COVID and control  volunteers to improve understanding, diagnosis and treatment of these diseases. The You + ME Registry and Biobank is a collection of clinical and patient-reported data and  biological samples (e.g. blood) from people living with Myalgic Encephalomyelitis (also known  as chronic fatigue syndrome or ME/CFS), people with long-COVID and control volunteers. The  patient registry collates demographic and real-world, longitudinal symptom, patient-reported  outcomes, and treatment data from a global cohort into a centralized repository. The Registry  will also be linked to a biobank which is a place that stores tissues, blood or other samples  from participants. The combination of data and biological samples will be made available to  researchers so we can: (1) improve our understanding of the natural history, epidemiology,  pathogenesis, resilience/susceptibility factors, disease subsets, and treatment of ME/CFS and  long-COVID using a standardized set of demographic and longitudinal data; (2) build an  infrastructure and resource to support a range of future research into these diseases; (3)  increase opportunities for collaboration between patients, providers, researchers, and  industry.  Anyone 18 years of age and older is invited to sign up. After creating a profile and  completing an informed consent via an online portal, participants fill out a series of  surveys, including medical history, co-occurring conditions, symptoms, quality of life,  functional status, and treatments. Participants receive email reminders to complete follow-up  surveys to provide researchers with information about their health over time.  The Registry also includes a mobile tracking app co-created with the community that allows  participants to monitor at minimum five core symptoms of fatigue, brain fog, unrefreshing  sleep, and orthostatic intolerance (on a scale of 0: symptom absent - 4: very severe) as well  as any additional symptoms of their choosing, life factors, and activity. Individuals can  also capture data in narrative form using a journaling function. Participants are encouraged  to capture data every 3 days if possible, but can track as often as daily.  Registry data is stored in a secure, encrypted database. Data is anonymized before being made  available on a secure platform for research. Biosamples collected from participants are  labeled with a coded number to protect their privacy and confidentiality.  This project is supported by Solve ME/CFS Initiative. You can learn more and sign up at  youandmeregistry.com. Inclusion Criteria:  -  Patients with ME/CFS,  -  Those without ME/CFS  -  Patients with long-COVID  -  Patients with COVID who recovered. Exclusion Criteria:  -  Those who never had COVID

This project will evaluate sexual dysfunction in women who have had surgery for gynecologic  cancer. The subjects will complete a set of questionnaires about health, daily living, sexual  encounters, and pain before their surgery and three times following. Each subject will be  randomized to receive either lidocaine or a placebo that is applied vaginally immediately  prior to any sexual encounters for approximately 6 months while maintaining a journal of  sexual encounters and pain. The subjects and healthcare providers will be blinded to the  treatment randomization until intervention and data collection is complete. Total  participation will last up to one year from the date of enrollment. Subjects will visit the  clinic at the same time as regular cancer care visits, receive the blinded intervention and  complete the surveys. Once consented, subjects will complete nine short surveys (The Female Sexual Function Index,  The PHQ-9, the GAD-7, the Social Provision Score (SPS), Rosenberg's Body Self-Esteem Index,  the Severity of Posttraumatic Stress (PTS) Symptoms Scale, the Adverse Childhood Events  Index, the Short Form (SF)-12, and the Dyadic Adjustment Scale) at their initial visit,  assessing physical, psychological, and social elements related to sexuality.  Subjects will then have the tumor reduction surgery.  Twelve weeks after her surgery, each subject will be asked to complete the same nine-survey  packet.  Once the second packet is completed, subjects will be randomized to receive either aqueous  lidocaine (4%) or placebo with instructions to apply the solution to three cotton balls and  place them on the perineum/vaginal introitus for one minute prior to sexual intercourse.  Subjects will be educated on the use of this blinded intervention and be asked to keep a  diary of sexual encounters, including a simple pictorial pain scale for each encounter.  Subjects and providers are blinded to the assigned intervention.  Once subjects complete three months of perineal intervention, they will be asked at a  follow-up visit (12 weeks following randomization) to complete the survey packet for a third  time.  Subjects will then continue their perineal intervention, keep a diary of sexual encounters  with the pain scale and return after another three-month interval for a fourth completion of  the survey packet. Sexual encounter diaries and pain scale assessments will be collected and  their participation in the trial will conclude. Also at the time of this concluding follow-up  visit in the Gynecologic Oncology Clinic, patients will receive counseling by a gynecologic  oncologist regarding education about sexual dysfunction, the possibility of experiencing  sexual dysfunction, and a potential referral for further treatment of sexual dysfunction. The  subject will remain blinded to the randomized intervention until the conclusion of the study.  Subjects will be unblinded and informed of assigned intervention at the conclusion of the  study via a letter sent to their home address from the researchers. Inclusion Criteria:  -  Female  -  Age 18-99  -  Planned to undergo primary surgical treatment at the University of Iowa Hospitals and  Clinics for a suspected or proven diagnosis of ovarian, fallopian tube, peritoneal,  endometrial, or cervical cancer  -  Able to give informed consent and follow study procedures  -  No previous reactions to lidocaine applications  -  Performance Status of 0 or 1  -  Reports having engaged in vaginal intercourse at least once in the last 12 months Exclusion Criteria:  -  Failure to confirm invasive ovarian, fallopian tube, peritoneal, endometrial or  cervical cancer by pathology from primary biopsy or surgery (subjects will not be  eligible to continue the trial beyond the initial completion of the questionnaires)  -  Diagnosis of another malignancy within the past five years, excluding basal cell  carcinoma of the skin  -  Patients undergoing primary or adjuvant external pelvic radiation (excluding adjuvant  vaginal brachytherapy)  -  Previous reactions to lidocaine applications  -  Previous reactions to lidocaine for the subjects' sexual partner(s)

Vascular and myocardial inflammation are significantly increased in Acute Coronary Syndrome  (ACS) patients, are closely correlated to LDL-C levels, and are associated with these adverse  consequences in the post-ACS patient population. Serum proprotein convertase subtilisin/kerin  type 9 (PCSK9) levels are also increased in ACS, may raise LDL-C, and the investigators'  pre-clinical studies indicate that PCSK9 is also a potent inducer of vascular inflammation.  The addition of the PCSK9 antibody evolocumab, currently approved to lower LDL-C in certain  patient populations, to current medical therapies would appear to be of particular benefit in  patients with an ACS by markedly reducing LDL-C, stabilizing vulnerable plaque, and limiting  inflammation-associated myocardial cell loss and resultant dysfunction. Despite aggressive early intervention and current secondary prevention strategies, many  patients who survive hospitalization for an acute coronary syndrome (ACS) experience  subsequent unfavorable outcomes, including recurrent ischemic events and unfavorable cardiac  remodeling associated with progressive left ventricular dysfunction and congestive heart  failure. Vascular and myocardial inflammation are significantly increased in ACS patients,  are closely correlated with LDL-C levels, and are associated with these adverse consequences.  Serum proprotein convertase subtilisin/kerin type 9 (PCSK9) levels are also increased in  patients with ACS, may raise LDL-C, and the investigators' pre-clinical studies indicate that  PCSK9 is also a potent inducer of vascular inflammation. The addition of evolocumab to  current medical therapies may therefore be of particular benefit in these patients, by  markedly reducing LDL-C, stabilizing vulnerable plaque, and limiting inflammation-associated  myocardial cell loss and resultant dysfunction.  In this study, the investigators propose to test the effects of PCSK9 inhibition with  evolocumab on LDL-C reduction, vascular and myocardial inflammation, cardiac function, and  clinical outcomes in an ACS patient cohort.  The investigators propose a double-blind randomized study of 100 patients presenting with an  ACS (ST-Elevation- and Non-ST-elevation myocardial infarction). One hundred ACS patients will  be randomized to evolocumab, 420 mg or to placebo (50 in each group) during early  hospitalization and will also receive current guideline-directed ACS therapy. Lipid profiles,  including LDL-cholesterol levels, and traditional and novel serum markers of inflammation and  endothelial function will be measured at presentation, during the index hospitalization, and  at 30-day and six-month follow-up. Positron Emission Tomography (PET) scans to measure  myocardial and vascular inflammation and echocardiograms will be performed during the early  post-infarction period and at thirty days (PET and echocardiogram) and six-month  (echocardiogram) following randomization. Clinical outcomes, such as angina class, will also  be collected at the six-month follow-up visit.  The protocol and the primary and secondary lipid and inflammatory outcomes in this study are  identical to those in NCT03515304 and therefore the data in the two studies may be analyzed  together. Inclusion Criteria:  1. Age 25 to 90 years.  2. ST elevation myocardial infarction, with compatible symptoms and ECG changes.  3. Non ST elevation myocardial infarction, with a troponin I > 5ng/mL and with compatible  symptoms and ECG changes.  4. Permission of attending physician.  5. Ability to understand the risk, benefits, and alternatives of participation. Exclusion Criteria:  1. Scheduled for cardiac surgery.  2. Current treatment with a PCSK9 antibody.  3. Current participation in an intervention clinical trial.  4. Latex allergy  5. Previous adverse reaction to monoclonal antibodies  6. Non-English speaking  7. Female of childbearing potential. This is a female subject who has not used acceptable  method(s) of birth control (see below) for at least one month prior to screening,  unless the subject is sterilized or postmenopausal. Menopause is defined as: 12 months  of spontaneous and continuous amenorrhea in a female > 55 year of age.  -  Acceptable method(s) of birth control definition: One highly effective method  (methods that can achieve a failure rate of less than 1% per year when used  consistently and correctly)  -  Combined hormonal (estrogen and progestogen) contraception associated with  inhibition of ovulation (oral, intravaginal, transdermal)  -  Progestogen-only hormonal contraception associated with inhibition of  ovulation (oral, injectable, implantable)  -  Intrauterine device (IUD)  -  Intrauterine hormone-releasing system (IUS)  -  Bilateral tubal occlusion  -  Vasectomized partner  -  Sexual abstinence  8. Subject likely not to be available to complete all protocol-related study visits or  procedures.

Microcirculatory dysfunction appears to play a key role in the development of organ failure  leading to the death of patients with coronavirus disease 2019 (Covid-19). It is still  uncertain today whether this damage is secondary to direct viral infection of endothelial  cells or the consequence of the inappropriate inflammatory response induced by the infection.  The analysis of endothelial and microcirculatory dysfunctions and glycocalyx degradation  therefore appears to be necessary in the understanding of the pathophysiological mechanisms  of Covid sepsis and could play a role in the evaluation of the efficacy of certain  therapeutics which would aim at improving regional perfusion by decreasing microcirculatory  dysfunction.However, the analysis of microcirculatory failure, endothelial dysfunction and  glycocalyx degradation has so far only been evaluated in small cohorts, without quantitative  analysis of microcirculatory perfusion The study of pathophysiological mechanisms of cellular penetration of Severe Acute  Respiratory Syndrome Coronavirus 2 (SARS CoV-2) allows the understanding of organ failures  observed in COVID 19. In order to allow its fusion with the cell membrane, SARS-Cov-2 must  bind the Angiotensin Converting Enzyme 2 (ACE2) via its Spike protein. This process requires  the priming of the viral S protein by a cellular serine protease TMPRSS2. Thus, any cell  co-expressing these two receptors is a potential target for the virus. Among all the cells  for which this co-expression could be observed, endothelial cells and vascular pericytes seem  to be potential targets, whose infection could lead to the development of an endothelial  dysfunction responsible for microcirculatory dysfunction. In addition, inappropriate host  immune system response observed in Covid-19 with massive production of pro-inflammatory  cytokines as IL-6, TNF α and VEGF could lead to endothelial dysfunction through neutrophils,  monocytes and macrophages mobilization producing Reactive Oxygen Species that increase  endothelium and glycocalyx damages. The resulting pro-adhesive, pro-vasoconstricting and  prothrombotic effects could lead to vascular micro-thrombosis, capillary plugging and  impairment of capillary flow.  Whether endothelial dysfunction is caused by direct viral cell infection or pro-inflammatory  response is uncertain, but various studies have confirmed that endotheliopathy plays a key  role in pathophysiological mechanisms in Covid 19.  In the context of critical care, the evaluation of microcirculatory perfusion appears to be a  diagnostic tool of major importance. Indeed, microcirculatory dysfunction is directly  associated with increased organ failure and mortality in the ICU. In addition, many clinical  situations such as sepsis or hemorrhagic shock may be responsible for a loss of hemodynamic  coherence between macro and microcirculatory parameters. Thus, the correction of  macrohemodynamic parameters (arterial pressure, cardiac output, plasma lactate, central  venous oxygen saturation) may be associated with persistent microcirculatory hypoperfusion.  It thus appears essential to develop systems for assessing the microcirculation in order to  move towards resuscitation guided by microcirculatory objectives.  The aim of this study is to describe the sublingual microcirculation and to evaluate  endothelial dysfunction in critically ill patient with Covid-19, and to determine whether  there is a correlation between the severity of microcirculatory damage, endothelial  dysfunction and clinically important outcomes in ICU. The data will serve to develop  strategies for individualized management of high-risk patients screened with microcirculation  evaluation. Inclusion Criteria:  -  Adult patient (≥ 18 ans)  -  Affiliation to the French social security system  -  Patient admitted to ICU within 72 hours before inclusion  -  Patient presenting SARS-CoV-2 pneumonia diagnosed by CT scan or by COVID-19 PCR test Exclusion Criteria:  -  Lesions of the oral mucosa

Atrial fibrillation (AF) has been the most frequently occurring, sustained arrhythmia, which  causes significant morbidity and mortality. AF may not always be a totally random process. It  can be maintained by stable and rapid reentrant circuits resulting in fibrillary conduction  throughout the atria. During mapping of AF, difficulty is frequently encountered during the  identification of culprit sites and an analysis of the wave propagation particularly when the  electrogram signals demonstrate wide temporal and spatial disparities. Catheter ablation  targeting regions with fractionated potentials or high frequencies during AF, has been  previously proposed as a treatment strategy. However, the benefit of adjunctive CFAE (complex  fractionated atrial electrogram) ablation or linear ablation after successful PVI (pulmonary  vein isolation) was controversial based on the recent data from the Substrate and Trigger  Ablation for Reduction of Atrial Fibrillation Trial Part II (STAR AF II) trial. Therefore,  the optimal ablation strategy for persistent AF remains undetermined and an alternative  approach has to be explored. In this prospective trial, investigators will investigate the long-term efficacy of catheter  ablation of non-paroxysmal AF, based on selective atrial substrate modification (e.g.  wavefrom periodicity analysis, similarity, plus phase mapping) (1). The control group would  be PV isolation alone. The primary end point is long-term recurrence of atrial arrhythmias.  The secondary end points composite procedural termination, the safety of the procedure,  recurrence of multiple procedures, and change of atrial and ventricular function after  catheter ablation.  The inclusion criteria, exclusion criteria, stepwise catheter ablation procedures (PVI and  then substrate modification), and the follow-up procedure are the same as current treatment  approaches in patients with non-paroxysmal AF. Inclusion Criteria:  1. Patients who sign the informed consent forms, and allow to be followed.  2. Symptomatic AF refractory or intolerant to at least one Class 1 or 3 antiarrhythmic  medication.  3. Patients with persistent/permanent AF (sustained beyond seven days, or lasting less  than seven days but necessitating pharmacologic or electrical cardioversion).  4. Patients with age equal or greater than 20 years old regardless of gender. Exclusion Criteria:  1. The presence of a atrial or ventricular thrombus.  2. Patients who are allergic to or unsuitable for use with the contrast media.  3. Pregnant patients or patients who are unavailable to receive X-ray.  4. Patients with renal insufficiency.  5. Patients had autonomic nervous system disorder (e.g. respiratory apnea) or previous  catheter ablation in the LA or MAZE procedure.  6. Patients who do not need atrial substrate modification (patients with non-paroxysmal  AF respond to PVI in terms of procedural termination of AF).  7. Patients with age less than 20 years old or greater than 90 years old regardless of  gender.

As a result of our research, investigators could not find any study investigating the  effectiveness of complex decongestive physiotherapy (KBF) in lymphedema patients with  metabolic syndrome. Therefore, our aim is to compare the effectiveness of KBF in patients  with and without metabolic syndrome. This study was planned to investigate the effects of metabolic syndrome seen in patients with  lymphedema on the results of complex decongestive physiotherapy. Lymphedema is a chronic  disease characterized by the accumulation of protein-rich fluid in the interstitial space.  Among all the treatment approaches known in the field, Complex Decongestive Physiotherapy  (CDT) is accepted as the gold standard in the treatment of lymphedema. CDT is a treatment  approach consisting of manual lymph drainage, skin care, compression bandage and exercises.  In clinical studies conducted to date, the effectiveness of CDFT in the treatment of lower  and upper extremity lymphedema has been clearly demonstrated.  Metabolic syndrome is a medical term that describes the combination of various cardiovascular  risk factors such as insulin resistance, impaired glucose tolerance or diabetes mellitus,  obesity, abdominal fat accumulation, dyslipidemia, hypertension, and coronary artery disease.  Obesity, the cardinal component of the metabolic syndrome, is a well-known risk factor for  lymphedema, and increased body mass index (BMI) is associated with the frequency and severity  of lymphedema. Obesity often accompanies lymphedema due to the effect of lymphedema and the  characteristics of patients with lymphedema.  Our aim in this study, which was planned in the light of these data, is to examine whether  the presence of metabolic syndrome in patients with lymphedema changes the effectiveness of  CDT. Inclusion Criteria:  -  Those between the ages of 18-65,  -  To be diagnosed with lymphedema in the lower or upper extremities  -  Volunteering to participate in the study  -  Getting >24 points from the Standardized Mini mental test Exclusion Criteria:  -  Having a score of <24 on the Standardized Mini Mental Test  -  Finding any problem preventing communication

Cerebral Palsy (CP) is a neurodevelopmental dysfunction which is permanent, non-progressive,  and caused by brain insult or injury.Although the basic finding of CP is having motor  function problems, visual, auditory, cognitive and behavioural problems are also seen in  CP.Having these problems interfere the functional independence of children with CP, so their  daily life of activities is limited.One of the way of increasing the functional independence  of these children is providing them hand rehabilitation.In the event of having hand  rehabilitation, children would achieve more daily living skills.Although having hand  rehabilitation is crucial for these children, they would lose their motivation on this by the  time because rehabilitation is a long process,For that reason, new therapy techniques are  tried by therapists to motivate these children during their rehabilitation seances.Virtual  reality rehabilitation is one of these new techniques used for designing enjoyable and  effective seances.Especially leap motion sensors are preferred to create virtual environment,  because they are cheap, portable, touchless and easy to use.These sensors can detect hand  movements and recognize hand gestures by using infrared.Our study was aimed to investigate  the effect of fine motor grip studies in virtual reality environment on performance based  hand skills in children with CP.Thirty two children with CP (6-18) were included in this  study.Children were randomly assigned into two equal-sized groups: control and study  groups.Participants in both groups received a neurodevelopmental therapy program.The study  group additionally received virtual reality rehabilitation programme. In control group,  neurodevelopmental treatment was provided 45 mins,2 d/week for 2 successive months.In study  group, neurodevelopmental treatment was provided 30 mins and virtual rehabilitation programme  was provided 15 mins, 2 d/week for 2 successive months. To evaluate the performance based  hand skills; Box and Block Test, Nine Hole Peg Test and Pink Tower (Montessori) Test were  used. Cerebral palsy (CP) can be defined as a permanent, non-progressive, motor function, posture  and developmental disorder that causes movement limitation due to a lesion that can occur in  the brain due to prenatal, perinatal and postnatal reasons.Although the etiology of the  disease cannot be determined precisely, the reasons causing SP; It is stated that it occurs  in prenatal, perinatal and postnatal periods. Sometimes, more than one factor can be found  together.Another common problem in individuals with CP is seen in upper extremity functions,  and limiting upper extremity functions also affects the independence of daily living  activities. The condition of the hand in the early period of rehabilitation has an important  place for upper extremity functions in the future.In this respect, it is very important to  include a program to develop manual skills in the rehabilitation process in order to make  children with CP more independent in daily life activities.Neurodevelopmental Treatment  Approach, widely used in the treatment of children with Cerebral Palsy; It is a method that  tries to control sensorimotor components of muscle tone, reflexes, abnormal movement  patterns, postural control, sensory-perception and memory problems with special  techniques.Virtual reality is a three-dimensional simulation that makes you feel to be in any  "place" and provides this by giving various inputs to our sensory organs. According to motor  control and motor learning theory, it is important to carry out repetitive, target-oriented  studies that increase motivation in the rehabilitation of children with Cerebral Palsy and it  is important to include games and entertainment in the treatment program. To achieve this,  making virtual reality a component of rehabilitation can cause the treatment process to be  more functional and effective.Research has shown that computer games designed for a specific  purpose can increase the motivation of children to increase the use of the affected  extremities and positively improve the strength and functionality of the affected  muscles.Leap Motion Sensors have been developed to detect hand movements. It can detect the  movement of the hand by emitting infrared rays in a restricted area. Physiotherapists have  stated that virtual reality rehabilitation applied with Leap Motion Sensors can be an  effective method that increases motivation in the treatment process in children with special  needs.Our study was aimed to investigate the effect of fine motor grip studies in virtual  reality environment on performance based hand skills in children with CP.After the approval  of the ethics committee, children with cerebral palsy were included in the study.Parental  approval was obtained.Reports from Health Council was examined to check diagnosis of  children.The study was performed in three centers: University of Abant Izzet Baysal, Silivri  Rehabilitation Center and Reyhan Rehabilitation Center.Thirty two children with CP (6-18)  were included in this study.Exclusion criteria were; epilepsy history, cognitive problems,  visual impairment, having problem on holding and releasing the objects.Children were randomly  assigned into two equal-sized groups: control and study groups.Participants in both groups  received a neurodevelopmental therapy program.The study group additionally received virtual  reality rehabilitation programme.As a normal developmental treatment method, functional  skills exercises, inhibition of abnormal movement patterns, sensory-motor integration in  purposeful movements, stretching and strengthening exercises, and daily life activities were  trained.As a virtual reality treatment method, object catching, firefly, bee-batting games  were used, which improved performance-dependent dexterity by integrating leap motion sensors  into the laptop.In control group, neurodevelopmental treatment was provided 45 mins,2  days/week for 2 successive months.In study group, neurodevelopmental treatment was provided  30 mins and virtual rehabilitation programme was provided 15 mins, 2 days/week for 2  successive months.In virtual reality treatment, each game was studied for 5 minutes and 3  games for a total of 15 minutes.Before and after the study, tests that measure  performance-related dexterity were applied and the previous and next results of the groups  were compared.SPSS statistics program was used for statistical evaluation of data belonging  to participants.In statistical evaluations, p <0.05 was considered as significant.In the data  analysis of the study, in order to select the appropriate statistical analysis, whether the  distribution of the data is suitable for normal distribution was determined by the  "one-sample Kolmogorov-Smirnov" test."Independent T Test" was used to compare age, height,  body weight, the measures pre-treatment and post-treatment, .Gender and affected sides were  compared by using "Chi-Square Test". Inclusion Criteria:  -  Gross Motor Functional Level should be I or II. Exclusion Criteria:  -  Epilepsy  -  Visual Impairment  -  Cognitive Problem  -  Inability to hold and release the objects

Hyperuricemia is seen in about 20% of adults in the general population, Chronic  hyperuricemia, frequently manifesting as the gout, is a well-known risk factor of joint  damage but has been also linked to a variety of other pathologies mostly affecting the  cardiovascular system. The close relation between high uric acid concentration and increased  risk of cardiovascular disease has been reported for more than a century. Furthermore, many  studies reported a strong association between hyperuricemia, arterial hypertension, obesity  and cardiovascular diseases even in an absence of typical clinical manifestations of gout.  Several studies showed that the prevalence of hyperuricemia in patients with hypertension is  much higher than in the general population and may worsen after the onset of antihypertensive  treatment. That may indicate that hyperuricemia may be also caused by antihypertensive drugs.  In contrast to diuretics and nonselective beta blockers the agents that block the  renin-angiotensin-aldosterone system have had a neutral effect on serum uric acid. Several  clinical studies showed that losartan in contrast to other AT1-receptor agonists, may have  specific uricosuric properties and thereby can lower uric acid concentration. It has been  speculated that uricosuric effect could make losartan particularly useful for the treatment  of arterial hypertension associated with hyperuricemia and metabolic syndrome.  The uricosuric effect of losartan is most likely due to overlapping two different mechanisms  regulating the excretion of uric acid. Losartan may increase uric acid tubular secretion in  the same way as other inhibitors of the renin-angiotensin-aldosterone system, but in addition  it may specifically inhibit post-secretory resorption of uric acid in the proximal tubule.  The effect may be due to a specific structure of the losartan molecule. The urateanion  transporter is a monoammonium selective transporter, and the losartan molecule is mainly a  monoanion at normal pH range (as opposed to dianion e.g. eprosartan) and therefore is a good  substrate for the exchanger. However, this concept remains speculative since, e.g. irbesartan  which is also a monoanion has no consistent uricosuric effect.  Fructose, in contrast to other carbohydrates causes an increase of serum uric acid  concentration, which may facilitate the development of the metabolic syndrome. The study group included 16 patients (15F, 1M, mean age 64.5 ± 9.8 years). The patients  selected for the study fulfilled the AHA/NHLBI 2005 criteria of the meta-bolic syndrome [30]  and ESC/ESH criteria of arterial hypertension. The exclusion cri-teria included an  antihypertensive therapy with the renin-angiotensin-aldosterone axis blocking agent used  anytime during last 3 months, current or past therapy with SGLT2 inhibitor, GLP-1 agonist or  DPP4-inhibitor, suspected or confirmed secondary form of hypertension, estimated glomerular  filtration rate <60 ml/min/1.73 m2, chron-ic liver disease, acute infection, psychiatric  disorders, mean serum potassium con-centration at last three measurements <4.0 mmol/l, or  aspartate aminotransferase or alanine aminotransferase or creatinine kinase > x1.5 upper  range limit were excluded. Seven patients had diabetes mellitus of which 4 were treated with  insulin. Twelve pa-tients were receiving metformin. Waist circumference was measured on the  initial visit. Plasma lipids and blood glucose were measured in a fasting state during the  study.  The study was designed as a randomized, crossover, head-to-head comparative study.  Randomization was carried out using MS Excel random number generator. After qualification  each patient was randomly assigned to receive either losartan (Lorista, KRKA, Slovenia) or  eprosartan (Teveten, Solvay Pharmaceuticals, Austral-ia). The patients were taking all other  previously prescribed drugs in unmodified dos-es during the whole course of the study. Each  study drug was given in a random or-der as a single morning dose (50 mg of losartan or 600 mg  of eprosartan) for two periods each lasting 3 months separated by 2-week wash-out time.  Oral fructose tolerance with the administration of 75 g of fructose was con-ducted 3 times  during the study in each patient, i.e. at baseline and after each of the treatment periods.  Before the commencement of OFTT, the patients collected the urine for 2 hours for assessment  of the urinary excretion of uric acid and creatinine. Other baseline measurements included  blood pressure, serum concentration of glu-cose, uric acid, creatinine and plasma lipids  (total, HDL- and, LDL-cholesterol and triglycerides). Subsequent blood samples were taken  three times during each OFTT, i.e. after 30, 60 and 120 minutes from its start to determine  serum uric acid concen-tration. In addition, peripheral blood pressure was measured before  the collection of each blood sample. After 120 minutes blood was also taken to assess plasma  lipids. The second timed 2-hour urine collection was obtained during OFTT. The same  pro-cedures were repeated after each treatment period. The patients took all their  pre-scribed medication including the study drug in the morning 120 minutes before the  beginning of OFTT Routine automated laboratory tests were used to assess blood and urine  pa-rameters. Blood pressure was taken in a sitting position with the aneroid  sphygmo-manometer. Blood pressure was measured both at baseline and after 3-month ther-apy  with each study drug. The mean from four measurements obtained between 0 and 120 minutes OFTT  was taken for the analysis. Blood pressure was measured by a designated single member of the  staff. Mean blood pressure (MAP) was calculated for all measurements as diastolic BP + 1/3 of  pulse pressure (systolic BP - diastolic BP).  The results are expressed as mean ± SD or median with interquartile range depending on each  variable distribution. 95% confidence intervals were calculated for the changes of the  parameters caused by the treatment. Statistical significance was defined at p<0.05. The  within-group comparisons were analyzed using one-way ANOVA and t-test for normally  distributed variables or alternatively with non-parametric Wilcoxon test. The normality of  the variable distribution was checked with Shapiro-Wilk test. The Pearson or Spearman  correlation coefficient was used to as-sess the relations between variables depending on  their distribution. Area under the curve (AUC) of serum uric acid during oral fructose  tolerance test was calculated using the trapezoidal rule. Inclusion Criteria:  -  Age 18 years old  -  Fulfillment of three or more of the AHA / NHLBI 2005 assessment criteria for the  metabolic syndrome:  -  abdominal obesity (i.e. handling in women ≥88 cm) male ≥ 102 cm  -  concentration of triglycerides in the form ≥150 mg / dl  -  concentration of HDL fraction (men <40 mg / dL, women <50 mg / dL)  -  blood pressure ≥ 130/85 mmHg  -  Correction of fasting glucose ≥100 mg / dL)  -  Written and informed consent to participate in the case of Exclusion Criteria:  -  Congenital defects in fructose metabolism (hereditary fructose intolerance and  idiopathic fructosuria)  -  Mental illness, dementia  -  Insufficient cooperation with the patient, non-compliance with doctor's  recommendations  -  Pregnancy  -  Bilateral renal artery stenosis or stenosis to a solitary kidney and other  contraindications for angiotensin receptor antagonists  -  Chronic use of uricosuric drugs, xanthine oxidase inhibitors and AT1 receptor  inhibitors

Stroke is one of the leading causes of death and disability-adjusted life-years worldwide.  Carotid high-risk atherosclerotic plaques are considered to be one of the major sources of  ischemic stroke. The present study aimed to investigate the relationship of carotid plaque  characteristics with brain perfusion and cognitive function in patients undergoing carotid  endarterectomy. Cerebrovascular disease is the first cause of death and adult disability in China. More than  75% of the patients in China have ischemic cerebrovascular disease, and about 33.3% of them  have ipsilateral extracranial carotid stenosis. One of the main causes of carotid stenosis is  atherosclerosis. Atherosclerotic plaques can be divided into two types: stable plaques and  vulnerable plaques. Vulnerable plaque has the tendency to rupture, prone to thrombosis and  rapid progression of dangerous plaque. Its pathological characteristics are mainly as  follows: thin fibrous cap (or fibrous cap has been broken), large lipid nucleus, massive  hemorrhage in plaque, rich in inflammatory cells, abundant neovascularization and plaque  surface calcification. Vulnerable plaque is the main cause of stroke. At present,  high-resolution magnetic resonance imaging combined with multi sequence is one of the best  methods to evaluate carotid artery stenosis, which is helpful to analyze plaque  characteristics.  At present, the main treatment methods of carotid artery stenosis are: carotid endarterectomy  (CEA) and carotid angioplasty with stenting (CAS). Large scale multicenter prospective  randomized trials and meta-analysis have established CEA as the gold standard for the  treatment of carotid arerosclerotic stenosis.  Studies have shown that the ipsilateral cerebral perfusion is continuously decreased due to  carotid artery stenosis, and CEA operation can relieve the vascular stenosis and improve the  cerebral perfusion. However, the relationship between cerebral perfusion improvement after  CEA and the quantitative characteristics of vulnerable plaque is still lack of sufficient  evidence. Vascular cognitive impairment is closely related to the progress of carotid  stenosis. The main mechanisms are microemboli formation, white matter injury and central  nervous function decline caused by long-term chronic hypoperfusion. The formation and  continuous hypoperfusion of microemboli further increase the burden of white matter disease.  Studies have shown that the visual spatial executive ability, naming ability, attention  ability and abstract profile ability of patients after CEA are significantly improved.  However, there is still insufficient evidence about the relationship between the MRI features  of vulnerable carotid plaques and the improvement of cognitive function after CEA.  We hope to achieve the following goals: 1) to explore the associations between carotid  vulnerable plaque characteristics and cerebral perfusion in patients undergoing CEA; 2) to  explore the associations between the characteristics of vulnerable carotid plaques and  cognitive function in patients undergoing CEA. Inclusion Criteria:  1. Over 30 years old;  2. The patients with symptomatic (>50%) or asymptomatic carotid stenosis (> 70%) measured  by computed tomography angiography (CTA) or B-mode ultrasonography  3. CEA operation will be performed in our hospital. Exclusion Criteria:  1. The history of CEA operation in the last 3 months;  2. Diseases (AF, valve diseases, etc.) that may cause cardiac thrombosis;  3. Contraindications of MR examination (vascular stent implantation, pacemaker, metal or  magnetic plants in vivo, claustrophobia, etc.) were found;  4. Contraindications of contrast agents: such as renal failure, iodine or gadolinium  contrast agent allergy;  5. Having heart or respiratory failure;  6. Serious consciousness disorder (coma, etc.);  7. Brain tumor;  8. Acute cerebral hemorrhage;  9. Pregnant women or planned pregnancies in the past 2 years;  10. Who does not agree to sign the informed consent.

The device that is the subject of this investigation is a diagnostic tool to detect the among  of fluid in hypodermis to help to prevent the formation of pressure injuries. The Sub  Epidermal Moister(SEM) Scanner, is a non invasive portable medical device use to complet the  clinical jugement of clinician The device that is the subject of this investigation is a diagnostic tool to detect the among  of fluid in hypodermis to help to prevent the formation of pressure injuries. The Sub  Epidermal Moister(SEM) Scanner, is a non invasive portable medical device use to complet the  clinical jugement of clinician.  The study "RELIASEM" will study hospitalized patients with high risk of Pressure Injurieswith  the next conditions:  For each patient 14 mesures: 6 on the sacrum, 4 on the right heel and 4 on the left heel.  This set of measure will be realized 2 timesby 4 different evaluator. To will have been  trained in the use of the SEM Scanner where as the other will be novice.  The main objective of this study is to determine on a risk population the intra- and  inter-examiner reliability of the SEM Scanner Inclusion Criteria:  -  Aged over 18  -  Taken the full-hospital care in physical and rehabilitation Medicine  -  Patient affiliated with a social security scheme  -  In the case of curatorship, patient have read the patient information document and  given his consent free and informed, in the presence of his/her curator  -  In the case of guardianship, legal representative have to had read the legal  representative information document for major placed under legal protection (under  guardianship) and given his consent free and informed for the person for whom he is  responsible (if the patient is agree), Exclusion Criteria:  -  Patient who objected his opposition during the exam  -  Patient who have one or more presure ulcer on at list one of the measuring area  -  Patient who has had a lower limb amputation  -  Pregnant, post natal period or breastfeeding women,  -  Person deprived of liberty by judicial or administrative decision

This is a phase 2, Simon's 2-stage designed study with 2 cohorts of anti-PD-1/PD-L1  experienced patients with untreated brain metastases: 1) melanoma and 2) renal cell carcinoma  (RCC). This is a phase 2, Simon's 2-stage designed study with 2 cohorts of anti-PD-1/PD-L1  experienced patients with untreated brain metastases: 1) melanoma and 2) renal cell carcinoma  (RCC). The primary endpoint of this study is to determine the best intracranial response of  combined pembrolizumab and lenvatinib in patients with untreated brain metastases from  melanoma or RCC who are anti-PD-1/PD-L1--experienced. Secondary endpoints include best  overall objective response (combined intracranial and extracranial response),  progression-free survival (PFS), overall survival (OS), duration of intracranial response,  and rate of adverse events. Exploratory/correlative endpoints will include evaluation of  pre-treatment tumor tissue (either intracranial or extracranial) for immunohistochemical  markers (PDL-1, tumor infiltrating lymphocytes, and angiogenic factors) and genetic analysis  of tumor mutations or mutational burden. Pre-treatment and on-treatment blood samples will be  collected and evaluated for biomarkers of response by cytokine profiling and transcriptomic  analysis.  Patients must have at least one evaluable asymptomatic intracranial lesion, no smaller than  5mm and no larger than 3 cm. Patients may have prior radiation to or surgical resection of a  symptomatic brain metastasis as long as at least one untreated lesion or unequivocally  growing lesion is present for response assessment. Pembrolizumab 200mg IV every 3 weeks will  be administered in combination with lenvatinib 20 mg PO daily for up to 2 years.  Patients must have received at least 2 doses of an anti-PD-1/PD-L1 mAb at some point in their  treatment course and must have unequivocal intracranial progression. Intracranial progression  in patients who are anti-PD-1/PD-L1 experienced is defined as either development of a new  brain lesion(s) or unequivocal progression in a previously irradiated or resected brain  lesion(s) site. Patients can be deemed to have progression after discussion and group  consensus of the case at tumor board. Secondary imaging assessments to confirm intracranial  progression are not required.  Patients who are enrolled from sites outside of the Sponsor (Yale) must have patient  eligibility approved by the Sponsor.  Archival tissue from extracranial and/or CNS metastases will be obtained, if available, for  correlative studies. A baseline pre-treatment fresh biopsy will also be required from an  accessible metastasis unless there is not an easily accessible site to biopsy or if a biopsy  is determined to be unfeasible by the treating physician after discussion with the study PI.  The tumor tissue will be studied retrospectively for PD-L1 expression, TIL characteristics,  and other immune and angiogenic markers that may predict sensitivity to this drug  combination.  First response assessment will be performed at 6 weeks and will include MRI of the brain and  CT body scans (or other clinically indicated body imaging such as MRI or PET CT) to assess  systemic disease. Brain metastasis response will be determined using modified RECIST  (mRECIST) 1.1 criteria, and extracranial disease response will be determined using RECIST  1.1. Responses will be confirmed with repeat imaging done at 12 weeks. Subsequent imaging  will be performed at 12-week intervals thereafter and include an MRI of the brain along with  body imaging, which may include CT, MRI, or PET/CT, as clinically indicated. Patients will  discontinue treatment for disease progression, unacceptable toxicity, patient withdrawal from  the study, termination of study, or death. Patients may be treated beyond progression of  intracranial metastases after consultation with the study PI, provided symptomatic lesions  are treated with stereotactic radiosurgery (SRS) or surgery. Dose reduction of pembrolizumab  for immune-related toxicities is not permitted. Dose-reduction of lenvatinib for related  toxicities is permitted.  Number of Patients:  A total of up to 62 eligible patients will be enrolled (27 patients with melanoma with  allowance for 3 additional patients if any are unevaluable and 29 patients with RCC with  allowance for 3 additional patients if any are unevaluable). Either cohort can be stopped for  futility according to Simon's two-stage design. The study will accrue for approximately 36  months and will be open for approximately 24 additional months as patients on study are  followed. Inclusion Criteria:  1. Male/female participants who are at least 18 years of age on the day of signing  informed consent with histologically confirmed diagnosis of melanoma or RCC and  untreated metastatic brain disease will be enrolled in this study.  Male participants: A male participant must agree to use a contraception as detailed in  the protocol during the treatment period and for at least 120 days after the last dose  of study treatment and refrain from donating sperm during this period.  Female participants: A female participant is eligible to participate if she is not  pregnant, not breastfeeding, and at least one of the following conditions applies:  1. Not a woman of childbearing potential (WOCBP) OR  2. A WOCBP who agrees to follow the contraceptive guidance per protocol during the  treatment period and for at least 120 days after the last dose of study  treatment.  2. The participant (or legally acceptable representative if applicable) provides written  informed consent for the trial.  3. Have histologic or cytologic confirmation from any body site of metastatic melanoma  irrespective of BRAF mutation status or renal cell carcinoma irrespective of  histologic subtype.  4. Patients who have had prior resection or biopsy of a CNS and/or extracranial  metastasis will be required to provide a formalin-fixed, paraffin embedded (FFPE)  specimen from tumor taken at the time of surgery, if available. Fresh biopsies of a  metastatic lesion should be performed if clinically able.  Note: Participants are not required to have new or repeat brain metastasis biopsies  for enrollment on the trial.  Note: For those who have never had CNS brain metastasis biopsies, tissue of an  accessible extracranial lesion will be obtained pre-treatment, unless deemed not  possible by the treating physician and upon discussion with PI. In this case, archival  extracranial metastatic tissue will be suitable.  5. Have at least one brain metastasis that is at least 5 mm AND twice the MRI slice  thickness, but less than or equal to 3 cm, which is asymptomatic, has not been  previously radiated, and is not requiring immediate local therapy or steroids. Lesions  situated in a previously irradiated area are considered allowed if measurable per the  aforementioned criteria and if progression has been demonstrated. Patients with any  lesion(s) >3 cm can be enrolled provided the following: (1) the lesion must receive  local treatment prior to initiation of study drugs (either by stereotactic  radiosurgery or resection), (2) the patient is not symptomatic from the lesion(s) once  local therapy has been administered, and (3) at least one additional, non-treated  lesion between 5 mm and 3 cm is still present.  6. Prior treatment for either the Melanoma or RCC cohorts may include: Patients must have  received at least 2 doses of an anti-PD-1/PD-L1 drug at some point in their treatment  course. Any number of prior treatments including PD-1/PD-L1 inhibitors are allowed.  Anti-PD-1/PD-L1 does not have to be the most recent therapy. Patients with melanoma  who developed brain metastasis within 6 months of the last dose of adjuvant anti-PD-1  can be enrolled.  7. Life expectancy of at least 3 months.  8. A history of radiotherapy for brain metastases is allowed up to 1 week before study  treatment provided that neurologic sequelae are resolved, and that measurable  untreated target lesion(s) remain.  9. Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1.  Evaluation of ECOG is to be performed within 7 days prior to the date of allocation.  10. Adequately controlled blood pressure (BP) with or without antihypertensive  medications, defined as a systolic BP ≤150 or a diastolic BP ≤90 mmHg at screening and  on Cycle 1 Day 1.  Note: Eligibility of a participant that is receiving ≥3 antihypertensive medications  prior to study entry will require PI approval.  11. Have adequate organ function as defined in the protocol. Specimens must be collected  within 10 days prior to the start of study treatment. Exclusion Criteria:  1. Symptomatic melanoma or RCC brain metastases at the time of therapy initiation.  2. Active use of corticosteroids to control CNS symptoms, unless steroid requirement has  been decreasing and currently on ≤10 mg of prednisone or its equivalent without CNS  symptoms for 7 days or more.  3. Overt hemorrhage from CNS metastases.  4. Presence of leptomeningeal disease.  5. Unable to undergo MRI imaging (either due to such conditions as inability to lie flat  for the scan duration, incompatible medical devices at risk for malfunction, and  foreign metal objects that pose a safety risk for imaging).  6. A WOCBP who has a positive urine pregnancy test within 72 hours prior to allocation.  If the urine test is positive or cannot be confirmed as negative, a serum pregnancy  test will be required.  7. Has received anti-cancer therapy including investigational agents within 14 days prior  to allocation or less than 4 weeks from prior immunomodulating antibody (excluding  anti-PD1/PD-L1).  Note: Participants must have recovered from all AEs due to previous therapies to  ≤Grade 1 or baseline. Participants with ≤Grade 2 neuropathy, rash, and/or alopecia may  be eligible.  Note: If participant received major surgery, they must have recovered adequately from  the toxicity and/or complications from the intervention prior to starting study  treatment.  8. Has received prior CNS radiotherapy within 1 week of start of study treatment.  Participants must have recovered from all radiation-related toxicities and not require  corticosteroids.  9. Has received a live vaccine within 30 days prior to the first dose of study drug.  Examples of live vaccines include, but are not limited to, the following: measles,  mumps, rubella, varicella/zoster (chicken pox), yellow fever, rabies, Bacillus  Calmette-Guérin (BCG), and typhoid vaccine. Seasonal influenza vaccines for injection  are generally killed virus vaccines and are allowed; however, intranasal influenza  vaccines (eg, FluMist®) are live attenuated vaccines and are not allowed.  10. Is currently participating in or has participated in a study of an investigational  agent or has used an investigational device within 4 weeks prior to the first dose of  study treatment.  Note: Participants who have entered the follow-up phase of an investigational study  may participate as long as it has been 4 weeks after the last dose of the previous  investigational agent.  11. Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy  (in doses exceeding 10 mg daily of prednisone equivalent) or any other form of  immunosuppressive therapy within 7 days prior to the first dose of study drug.  12. Has a known additional malignancy that is progressing or is requiring active  treatment.  13. Has active autoimmune disease that has required systemic treatment in the past 3  months or a documented history of clinical severe autoimmune disease, or a syndrome  that requires chronic systemic steroids or immunosuppressive agents. Replacement  therapy (eg., thyroxine, insulin, or physiologic corticosteroid replacement therapy  for adrenal or pituitary insufficiency with prednisone < 10 mg or the equivalent,  etc.) is not considered a form of systemic treatment. Subjects with thyroid disease or  vitiligo will not be excluded from the study.  14. Has presence of gastrointestinal condition including malabsorption, gastrointestinal  anastomosis, or any other condition that might affect the absorption of lenvatinib.  15. Has a pre-existing Grade ≥3 gastrointestinal or non-gastrointestinal fistula.  16. Serious non-healing or dehiscing wound.  17. Has radiographic evidence of major blood vessel invasion/infiltration. The degree of  tumor invasion/infiltration of major blood vessels should be considered because of the  potential risk of severe hemorrhage associated with tumor shrinkage/necrosis following  lenvatinib therapy.  18. Has clinically significant hemoptysis or tumor bleeding within 2 weeks prior to the  first dose of study drug.  19. Has clinically significant cardiovascular disease within 6 months of the first dose of  study intervention including New York Heart Association Class III or IV congestive  heart failure, unstable angina, myocardial infarction, cerebral vascular accident, or  cardiac arrhythmia associated with hemodynamic instability.  Note: Medically controlled arrhythmia is permitted.  20. Has prolongation of QTc interval (calculated using Fridericia's formula) to >480 msec.  21. New York Heart Association congestive heart failure of grade II or above, unstable  angina, myocardial infarction within the past 6 months, or serious cardiac arrhythmia  associated with significant cardiovascular impairment within the past 6 months.  22. Has urine protein ≥2 g/24-hour. Note: Participants with >1+ proteinuria on urine  dipstick will undergo 24-hour urine collection for quantitative assessment of  proteinuria.  23. Evidence of a bleeding diathesis, risk for severe hemorrhage, or clinically  significant coagulopathy.  24. Uncontrolled hypertension (systolic BP >150 mmHg or diastolic BP >90 mmHg) in spite of  an optimized regimen of antihypertensive medication.  25. Has a history of (non-infectious, non-radiation-induced) pneumonitis not responsive to  steroids or has current pneumonitis. Patients will also be excluded if there are  respiratory issues including active infection or require supplemental oxygen for  activities of daily living.  26. Has an active infection requiring systemic therapy.  27. Has a known history of Human Immunodeficiency Virus (HIV).  28. Has a known history of Hepatitis B (defined as Hepatitis B surface antigen [HBsAg]  reactive) or known active Hepatitis C virus (defined as a detectable qualitative HCV  RNA level) infection.  Note: No testing for Hepatitis B and Hepatitis C is required unless mandated by local  health authority.  29. Has a history or current evidence of any condition, therapy, or laboratory abnormality  that might confound the results of the study, interfere with the subject's  participation for the full duration of the study, or is not in the best interest of  the subject to participate, in the opinion of the treating investigator.  30. Has known psychiatric or substance abuse disorders that would interfere with  cooperation with the requirements of the trial.  31. Is pregnant or breastfeeding or expecting to conceive or father children within the  projected duration of the study, starting with the screening visit through 120 days  after the last dose of trial treatment.  32. Women of child-bearing potential who are unwilling to or unable to use an acceptable  method of contraception to avoid pregnancy for the entire study and for at least 5  months after cessation of study drug or have a positive pregnancy test at screening or  baseline, or who are pregnant or breast feeding.

VAP（Ventilator-associated pneumonia）is the most common complication of mechanical ventilation  in severely ill patients. VAP is defined as pneumonia occurring 48 hours after patients  receive mechanical ventilation, including pneumonia occurring within 48 hours after  extubation. It is one of the important causes of hospital-acquired infection, and the  incidence of VAP in children on mechanical ventilation is about 10%, or 7/1000 days of  mechanical ventilation, and the overall mortality is 10-24%.Research has so far explained the  relationship between bacteria isolated from human biological samples and VAP pathogens. Most  studies are limited to the level of bacterial species, and there are few reports on bacterial  genotyping, and there is a lack of scientific basis for the pathogenesis of VAP caused by  bacteria in ventilator pipeline. The aim of the study is to investigate pathogen of the  sputum in deep respiratory tract of patients with mechanical ventilation in PICU by the means  of second generation sequencing (NGS). Children receiving invasive mechanical ventilation in the intensive care unit (PICU) of the  Pediatric Hospital of Fudan University will be included. Deep sputum samples were collected  within 24 h and on day 5 of mechanical ventilation, respectively, and sent for NGS at the  same time. Sputum etiology examination is performed with sputum culture blood free DNA test.  The basic clinical data of the children (age, sex, weight, PICU diagnosis and other basic  information, as well as the time of start and end of invasive mechanical ventilation for  basic diseases, Glasgow coma score (GCS score), 3rd generation pediatric mortality risk score  III(Prism III score), CRP, PCT, white blood cell count and body temperature will be recorded。  Clinical data related to the use of glucocorticoids, antibiotics and other drugs as well as  life support such as renal replacement therapy, extracorporeal membrane, lung oxygenation and  other life support were collected. Time and method of diagnosis of VAP pathogens were  collected.  By comparing sensitivity and specificity of NGS and conventional sputum specimens for  detection of VAP, the clinical value of mNGS in VAP will be studied. Inclusion Criteria:  -  The time of invasive mechanical ventilation was less than 24 h when admitted to PICU  Total duration of invasive mechanical ventilation is over 5 days Exclusion Criteria:  -  Participants in other clinical trials in the same period No Informed Consent signed

The purpose of this study is to investigate the effect of a telerehabilitation-yoga  intervention delivered remotely via videoconferencing on adults with Parkinson's Disease and  anxiety symptoms. A single group intervention study of adults (18-80 years-old) with Parkinson's Disease and  anxiety symptoms undergoing a 6-week intervention of 30-minute yoga classes delivered  remotely through videoconferencing 2-3 times per week. Subjects with symptoms of anxiety as  indicated by their score on the Parkinson's Anxiety Scale will complete yoga classes  delivered at-home with videoconferencing, receiving one-on-one yoga instruction including  breathing, postures, and meditation/relaxation for two-three times a week. Data collection  will occur remotely via videoconferencing at 0-weeks, 6-weeks after a waiting period,  12-weeks after the intervention, and 6-weeks after the last lab visit. Data collection will  include demographics, mental health questionnaires, motor assessments, enjoyment, usability,  and follow-up yoga status. Each yoga session will be video recorded to aide in recording  adherence, adverse events, and challenges. Inclusion Criteria:  -  diagnosis of Parkinson's Disease  -  symptoms of anxiety as indicated by PAS (score ≥ 14)  -  18-80 years old  -  ability to communicate verbally and follow directions  -  English-speaking  -  access to WiFi and applicable technological device (computer, laptop, tablet,  smartphone etc.)  -  willing to be video recorded during the yoga session  -  willing to open Zoom on their technological device  -  demonstrates self-reported technological literacy. Exclusion Criteria:  -  major depressive disorder (self-report medical history)  -  injury or condition that could prevent engagement in yoga poses  -  cognitive impairment or condition that would prevent the participant from  understanding the tasks or communicating with the research team  -  past yoga experience exceeding 5 or more times within the last 2 months  -  pregnant women (self-report)

This is a formative research study to test a culturally-centered, program-level  implementation intervention to increase the use of medications for opioid use disorder in  four healthcare and addiction specialty treatment sites serving American Indian and Alaska  Native communities. This is a formative research study to test a culturally-centered, program-level  implementation intervention to increase the use of medications for opioid use disorder (MOUD)  in four healthcare and addiction specialty treatment sites serving American Indian and Alaska  Native communities. The study design is a cluster randomized stepped wedge implementation  trial with two steps, and two sites per step (N=4 sites). Study design and methods are  informed by the Consolidated Framework for Implementation Research (CFIR) and the RE-AIM  framework (Reach, Effectiveness, Adoption, Implementation, Maintenance). The primary outcome  of the trial is the number of consumers with OUD initiated onto MOUD (i.e., buprenorphine,  extended-release naltrexone, or methadone) in the 6 months after intervention delivery  (compared to the 6 months before intervention delivery) - capturing implementation  intervention Reach. The primary outcome will be measured at the end of the six-month  implementation stage and compared to the pre-intervention observation phase (prior to  delivery of the implementation intervention). Primary data collection will use de-identified  data from the electronic medical records (EMR) at each site beginning with data from the six  months prior to intervention delivery for Step 1 sites and 12 months prior for Step 2 sites.  For Step 1 sites, some secondary outcomes will also be assessed during the sustainment stage  (the six months following implementation). As part of the study, consumers with OUD will be  asked to participate in additional assessments and provide informed consent. Enrolled  consumer participants will be asked to complete four assessment visits (baseline, week 4,  week 8, and week 12) to collect comprehensive information about mental health, cultural  connectedness and spirituality, social functioning, and experiences with and acceptability of  OUD treatment. Providers at each clinical site will also be asked to complete surveys at  three time points to assess attitudes, knowledge, and readiness related to MOUD. Inclusion Criteria:  -  Willing and able to provide informed consent  -  English comprehension and proficiency  -  Receiving services at a participating study site  -  Meet criteria for a current opioid use disorder  -  Self-identify as American Indian or Alaska Native  -  Willing to have program data linked to assessment data  -  18 years or older Exclusion Criteria:  -  participation in research assessments contraindicated

1. To detect the efficacy and safety of combined TCA and MDA in treating melasma.  2. To compare the efficacy and safety of using different TCA concentrations (15% & 20%)  alone and in combination with MDA in treatment of melasma. Melasma is a common, acquired hypermelanosis that occurs in sun exposed areas, mostly on the  face, occasionally on the neck, and rarely on the forearms.  Melasma is generally a clinical diagnosis consisting of symmetric reticulated hypermelanosis  in three predominant facial patterns: Centro facial, malar, and mandibular The major clinical  pattern in 50-80% of cases is the Centro facial pattern, which affects the forehead, nose,  and upper lip .  The malar pattern is restricted to the malar cheeks on the face, while mandibular melasma is  present on the jawline and chin .  A newer pattern termed extra-facial melasma can occur on non-facial body parts, including the  neck, sternum, forearms, and upper extremities .  Using the Wood's light examination, melasma can be classified into four major histological  types depending upon the depth of pigment deposition:The epidermal type, in which the  pigmentation is intensified under Wood's light, is the most common type. The epidermal type  is the most responsive to treatment.  Key etiologic factors include a genetic predisposition, solar damage, barrier abnormalities,  and unique sensitivities to hormonal changes including pregnancy, oral contraceptives, and  hormone replacement therapy.  Melasma is often difficult to treat, and the condition may be refractory. Despite a strong  therapeutic demand, the treatment of melasma remains highly challenging with inconsistent  results and almost constant relapses. The treatment of melasma should include a multimodality  approach that incorporates photoprotective agents, antioxidant treatments, skin lighteners,  exfoliants, and resurfacing procedures, as needed. Evidence-based studies suggest that first  line therapies for melasma encompass intense photoprotection and topical lightening agents.  Many depigmenting agents and other therapies such as chemical peeling are used for treating  melasma, in the form of mono or combined therapy .  The most commonly used peeling agents are alpha-hydroxy-acids, glycolic acid, Jessner  solution, salicylic acid, trichloroacetic acid (TCA), pyruvic acid and phenol .  Chemical peelings are used on a wide scale in cosmetic field including melasma treatment.  They often provide clinicians with flexibility in tailoring treat- ments according to patient  needs and satisfaction Chemical peelings are used on a wide scale in cosmetic field including  melasma treatment. They often provide clinicians with flexibility in tailoring treat- ments  according to patient needs and satisfaction Chemical peelings are used on a wide scale in  cosmetic field including melasma treatment. They often provide clinicians with flexibility in  tailoring treat- ments according to patient needs and satisfaction. Chemical peelings are  used on a wide scale in cosmetic field including melasma treatment. They often provide  clinicians with flexibility in tailoring treat- ments according to patient needs and  satisfaction.  Chemical peeling is a promising treatment for numerous pigmentary disorders as melasma. It  aims to remove the melanin rather than the inhibition of melanocytes or melanogenesis by  causing controlled necrosis and subsequent regeneration of the epidermis, apart from  remodeling of collagen and elastic fibers in the dermis .  TCA is widely used peeling agent in treatment of hyperpigmentation especially melasma. It is  a keratolytic acid which cause precipitation of proteins and coagulation necrosis of the  epidermis that leads to reepithelization with replacement of smoother skin with an even skin  tone .It is not expensive, stable, not light-sensitive and does not need to be neutralized .  Microdermabrasion (MDA) is a minimally invasive epidermal resurfacing procedure used to treat  uneven skin tone/texture, photo aging, striae, melasma, and scars.Microdermabrasion uses a  variable flow of vacuum suction to maintain contact with the skin whilst the crystals (or  diamond tips) get to work by smoothing and buffing the skin's surface.The crystals (or  diamond tips) cause gentle mechanical abrasion to the skin, which ultimately removes the  stratum corneum layer of the epidermis. As part of the wound healing process, new epidermis  forms with enhanced cosmoses. The technique is considered safe for all Fitzpatrick skin types  and complications are minimal. In addition to the cosmetic benefits of MDA, studies have also  shown improved skin permeability and enhanced delivery of transdermal medications dosed on an  area of the skin treated with MDA. Microdermabrasion removes the stratum corneum, the  outermost layer of the epidermis . MDA has also been shown to affect deeper layers of the  epidermis and dermis. MDA causes a re-arrangement of melanosomes in the basal layer of the  epidermis, flattening of rete ridges at the dermal-epidermal junction, increased collagen  fiber density at the dermal-epidermal junction, and vascular ectasia in the reticular dermis  . Inclusion Criteria:  1. Adults of 18 years and above with bilateral melasma  2. Clinical diagnosis of melasma.  3. Mental capacity to give informed consent. Exclusion Criteria:  1. Pregnant or nursing women  2. Current use of hormonal birth control medication or any hormonal therapy  3. History of laser or dermabrasion to the face within 9 months of study enrollment  4. Patients with poor wound healing, recurrent herpes simplex and current skin infection  (facial warts, molluscum contagiosum) and history of hypertropic scar/keloids  5. Photosensitivity.  6. Patients with unrealistic expectations All the included patients will be subjected to  detailed history taking,dermatological examination and Wood's light examination to  estimate the depth (epidermal, dermal or mixed) of melasma.

After exposure, rabies can be prevented in almost 100% of cases by the administration of  sufficient and timely post-exposure prophylaxis (PEP). PEP is based on wound cleansing,  antisepsis, administration of rabies vaccine as well as rabies immunoglobulin, if reviewed.  However, anti-rabies PEP remains too often out of financial and / or geographic access,  especially for poor and / or rural populations in endemic countries who remain the most  exposed to the risk of contracting rabies. Two major studies planned in Cambodia between 2014  and 2018 - the RESIST 0/1 clinical - epidemiological study and the RESIST-2 study on the  antibody response to the vaccine - provided the basis that allowed a change in international  recommendations on PPE. Since April 2018, the new "IPC protocol" of three sessions of reduced  double doses (0.1 mL x 2) administered intradermally (ID) over one week has replaced the  already very effective "TRC protocol" of four sessions over one month which was the reference  dose-sparing protocol for endemic countries until 2018. It remains to be determined whether  the IPC protocol (3 sessions / 1 week) confers long-term immunity equivalent to that obtained  after a TRC ID protocol (4 sessions / 1 month). This question is of importance to public  health decision-makers and clinical teams in endemic countries who would hesitate to switch  to the abbreviated IPC protocol. This is a multicenter, randomized, non-inferior clinical trial with samples for examinations  and vaccination booster.  To achieve this study, persons who previously received PEP and of any age (including  children), gender or medical condition (including pregnant women) and whichever the status of  the dog which bit at least 2, 5 or 10 years ago will be contacted and invited to participate  to the study.  This study will take place in two centers :  -  The rabies prevention center at Institut Pasteur du Cambodge  -  The rabies prevention center at Institut Pasteur de Madagascar. The study will be  coordinated by Institut Pasteur in Paris which will subsequently conduct the analysis in  collaboration with researchers at Institut Pasteur du Cambodge and Institut Pasteur de  Madagascar.  This study will take place in two visits :  -  the first visit (day 0) : after receiving consent from the participants, the member of  the investigating team will perform the blood sample, followed by a single session of  two intradermal doses of 0.1 mL. The investigators will also carry out measurements and  complete the questionnaire with the participant.  -  the second visit (day 7) : a follow-up visit will be performed by a member of the  investigating team who will perform a second blood sample to all the participants to the  study. The investigator will complete a second paper CRF with the participants to  document any unwanted effects which may have occurred during the seven days between the  inclusion visit and the follow-up visit. Inclusion Criteria:  -  person Identified in IP Cambodia or IP Madagascar records for having received ID PEP  by 4 sessions/1 month or 3 sessions/1 week at least two, five or 10 years earlier,  with no rabies boosting since that time;  -  person Who received information adapter to his/her age and who signed the consent form  (or his/her legal tutors) Exclusion Criteria:  -  person who received Rabies vaccine booster since the earlier PEP  -  person with allergy or other severe unwanted effect at the time of the earlier PEP

This research trial studies cell-free deoxyribonucleic acid (DNA) and ribonucleic acid (RNA)  in blood from patients with prostate cancer that does not respond to hormone therapy and has  spread to other places in the body. Studying samples of blood from patients with prostate  cancer may help doctors to learn more about the changes that occur in tumor cells over time  and how they become resistant to anti-cancer drugs. PRIMARY OBJECTIVES:  I. To document the appearance of androgen receptor isoform splice variant 7 (AR-V7)  expression over the course of therapy in castration-resistant prostate cancer (CRPC).  II. To determine whether detectable AR-V7 is associated with a shortened duration of  treatment benefit of abiraterone or enzalutamide.  SECONDARY OBJECTIVES:  I. To determine how the presence and expression level of AR-V7 impacts response to docetaxel.  II. To determine at what point AR-V7 arises during androgen deprivation therapy (ADT) and how  its presence and expression corresponds to castration resistance.  TERTIARY OBJECTIVES:  I. To determine if androgen receptor isoform splice variants (AR-Vs) other than AR-V7 play a  role in resistance and / or response to the therapies explored in this study.  II. To determine if, in patients who do not express mutations in androgen receptor (AR),  other genetic alterations are associated with treatment outcomes to the therapies explored in  this study.  OUTLINE:  Patients undergo blood collection every 4-12 weeks during ADT, abiraterone and / or  enzalutamide and docetaxel. Patients switched from ADT to either abiraterone or enzalutamide  during the study will undergo phlebotomy every 6-12 weeks. Samples are analyzed for cell-free  ribonucleic acid (cfRNA), cell-free deoxyribonucleic acid (cfDNA), AR-V7, and other AR-Vs via  quantitative reverse transcriptase-polymerase chain reaction (RT-PCR).  After completion of study, patients are followed up for 3 years. Inclusion Criteria:  -  A diagnosis of histologically confirmed prostate adenocarcinoma and falling into one  of the following 5 groups:  -  Currently receiving ADT (previously untreated for metastatic disease)  -  These patients will be grouped into 3 cohorts: having received ADT for 3-6  months; for 1-2 years; and for > 3 years  -  Scheduled to begin treatment with ADT (previously untreated for metastatic  disease)  -  Scheduled to begin treatment with enzalutamide (castration resistant / has  received ADT / may have received abiraterone)  -  Scheduled to begin treatment with abiraterone (castration resistant / has  received ADT / may have received enzalutamide)  -  Scheduled to begin treatment with docetaxel (castration resistant / has received  ADT / has received enzalutamide and/or abiraterone)  -  Have been diagnosed with either hormone-naive or castrate-resistant metastatic disease  -  Ability and willingness to provide written and informed consent Exclusion Criteria:  -  Patients who receive combined ADT with docetaxel for hormone-naive metastatic prostate  cancer  -  Patients on intermittent ADT

This pilot study will establish non-invasive sample collections, including breath, saliva,  blood and urine pre-surgery and at the participant's one-month post-surgery follow-up visit.  Participants with suspected non-small cell lung cancer (NSCLC) stage I-III will be recruited. Primary Objective  -  To evaluate the feasibility of adding non-invasive sample collections in the  pre-surgical setting and at the post-surgery follow-up visit.  -  To identify and assess metabolic and microbial signatures collected at pre- and  post-surgery and determine which are indicative of lung cancer.  Secondary Objective  -  To identify signatures which are associated with lung cancer stage.  -  To identify signatures which are impacted by patient's pulmonary function status. Inclusion Criteria:  -  Male and female patients age >18 years, of all racial and ethnic origins, with  suspected nonsmall cell lung cancer stages I, II, and III, as evident through  radiographic evidence and felt acceptable to undergo surgical resection.  -  Patients who have the ability to understand and the willingness to sign a written  consent form. Exclusion Criteria:  -  Patients who are have taken antibiotics within two weeks.  -  Patients who are on continuous supplemental oxygen.  -  Patients currently undergoing active treatment for other malignancies.  -  Subjects who are unable or unwilling to provide consent.

The purpose of this research study is to test the safety and effectiveness of docetaxel  chemotherapy and pembrolizumab plus adenoviral-mediated interleukin-12 (ADV/IL-12) gene  therapy in patients with anthracycline-refractory, triple negative breast cancer (TNBC). The purpose of this study is to learn how triple negative breast cancer (TNBC) responds to  the use of chemotherapy, pembrolizumab, and gene therapy together in patients who have  previously not responded to treatment. We will also look at the effects, good or bad, the  study therapy has on you and your TNBC.  Chemotherapy given before breast cancer surgery is called neoadjuvant chemotherapy. It  shrinks the breast tumor, so it is easier to remove during surgery. Docetaxel is often used  for the neoadjuvant treatment of breast cancer. Unfortunately, a lot of breast tumors do not  shrink with docetaxel chemotherapy treatment. Docetaxel chemotherapy is standard care for  TNBC.  Pembrolizumab is a type of treatment that stimulates your own immune system to attack cancer  cells. Your immune system is normally your body's first defense against threats like cancer.  However, sometimes cancer cells produce signals that prevent the immune system from detecting  and killing them. Pembrolizumab helps your immune system so it can detect and attack cancer  cells. Chemotherapy plus pembrolizumab has been shown to be better than chemotherapy alone  for shrinking breast tumors before surgery.  To help increase the tumor-shrinking activity of docetaxel chemotherapy and pembrolizumab,  you will be given more treatments, Interleukin-12 (IL-12) gene therapy This treatments will  be used to boost the cancer-fighting ability of your immune system. Thus, the use of IL-12  gene therapy with docetaxel chemotherapy and pembrolizumab may make your immune system work  harder to shrink your tumor. IL-12 is a substance that is normally made by certain immune  cells in the body. IL-12 stimulates T cells, a special type of immune cell in the blood, to  respond to threats to your body like cancer.  After you finish the study treatment, you will have your breast cancer surgery. Inclusion Criteria:  Patients are eligible to be included in the trial only if all of the following criteria  apply:  1. The patient (or legally acceptable representative if applicable) provides written  informed consent for the trial.  2. Female ≥ 18 years of age on the day of informed consent signing.  3. Histologically confirmed triple negative breast cancer is defined as estrogen receptor  (ER), progesterone receptor (PR), and HER2 negative. ER/PR negativity is defined as  <10% IHC staining of any intensity.  HER2 negativity is defined as the following per the 2018 American Society of Clinical  Oncology and College of American Pathologists guidelines.  4. Refractory to standard neoadjuvant anthracycline-containing chemotherapy regimen,  demonstrated on MRI.  5. Bilateral breast cancers that individually meet eligibility criteria are allowed.  6. Prior immunotherapy treatment allowed. 7. Eastern Cooperative Oncology Group (ECOG)  performance status of 0 or 1. 8. Adequate organ function as defined in Table 1. All  screening labs should be performed within 28 days of trial treatment initiation.  9. Cardiac ejection fraction ≥45%. 10. A female patient is eligible to participate if she  is not pregnant, not breastfeeding, and at least one of the following conditions applies:  1. Not a woman of childbearing potential (WOCBP) OR  2. A WOCBP who agrees to follow the contraceptive guidance in during the treatment period  and for at least 120 days after the last dose of trial treatment. WOCBP must have a  negative serum pregnancy test (β-human chorionic gonadotropin [β-HCG]) within 72 hours  prior to trial treatment administration.  11. Willing to provide biopsy tissue as required by the trial. 12. Willing and able to  comply with the protocol for the duration of the trial including undergoing treatment  and scheduled visits and examinations. Exclusion Criteria:  1. History of poorly controlled hypertension (defined as systolic blood pressure  >150 mmHg). Patients whose hypertension has been well controlled on the same  treatment for 1 year prior to Cycle 1, Day 1 are eligible. Only patients on  single-agent antihypertensive therapy are allowed.  2. History of New York Heart Association class III or greater cardiac disease.  3. History of myocardial infarction, stroke, ventricular arrhythmia, or greater than  first-degree conduction defect within the past 12 months.  4. History of congenital QT prolongation.  5. Absolute corrected QT interval of >480 msec in the presence of potassium >4.0  mEq/L and magnesium >1.8 mg/dL.  6. Is currently participating in or has participated in a study of an  investigational agent or has used an investigational device within 4 weeks prior  to trial treatment administration.  NOTE: Patients who have entered the follow-up phase of an investigational study may  participate as long as it has been 4 weeks after the last dose of the previous  investigational agent.  8. Concurrent use of any complementary or alternative medicines. 9. Concurrent use of  inhibitors or inducers of cytochrome P450 (CYP)3A4 and CYP2D6 10. Has a diagnosis of  immunodeficiency or is receiving chronic systemic steroid therapy (dose exceeding 10  mg daily of prednisone equivalent) or any other form of immunosuppressive therapy  within 7 days prior to trial treatment administration.  11. Known history of active tuberculosis (Bacillus Tuberculosis). 12. Known or  suspected hypersensitivity to any component or excipient of the proposed regimen  (docetaxel chemotherapy, gene vector, pembrolizumab).  13. Patients must have recovered from all AEs due to previous therapies to ≤ Grade 1  or baseline. Patients with ≤ Grade 2 neuropathy may be eligible. If patient received  major surgery, she must have recovered adequately from the toxicity and/or  complications from the intervention prior to starting the trial treatment.  14. Known additional malignancy that is progressing or requires active treatment.  NOTE: Patients with basal cell carcinoma of the skin, squamous cell carcinoma of the  skin, or cervical cancer in situ that have undergone potentially curative therapy are  not excluded.  15. Active autoimmune disease that has required systemic treatment in the past 2 years  (i.e., with use of disease-modifying agents, corticosteroids, or immunosuppressive  drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid  replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a  form of systemic treatment.  16. History of (noninfectious) pneumonitis that required steroids or current  pneumonitis.  17. Active infection requiring systemic therapy. 18. History or current evidence of  any condition, therapy, or laboratory abnormality that might confound the results of  the trial, interfere with the patient's participation for the full duration of the  trial, or is not in the best interest of the patient to participate, in the opinion of  the treating investigator.  19. Known psychiatric or substance abuse disorders that would interfere with  cooperation with the requirements of the trial.  20. Pregnant or breastfeeding, or expecting to conceive children within the projected  duration of the trial, starting with the prescreening or screening visit through 120  days after the last dose of trial treatment.  21. Known history of human immunodeficiency virus (HIV). 22. Known history of  hepatitis B (defined as hepatitis B surface antigen reactive) or known active  hepatitis C virus (HCV; defined as HCV RNA [qualitative] is detected) infection.  23. Received a live vaccine within 30 days prior to trial treatment administration.  Examples of live vaccines include, but are not limited to, the following: measles,  mumps, rubella, varicella/zoster (chicken pox), yellow fever, rabies, Bacillus  Calmette-Guérin, and typhoid vaccine. Seasonal influenza vaccines for injection are  generally killed virus vaccines and are allowed; however, intranasal influenza  vaccines (e.g., FluMist®) are live attenuated vaccines and are not allowed.

To compare the efficacy and efficiency of peribulbar block versus sub-Tenon's capsule  injection of local anesthetic in redo vitreoretinal surgery Sixty patients undergoing vitreoretinal surgery were randomized to receive either peribulbar  or sub-Tenon's capsule injection of 8 ml of a 20:80 mixture of 2% lidocaine and 0.5%  bupivacaine with 60 IU hyalouronic acid.  The primary outcome measured was intraoperative eye pain, which was rated by patients in both  groups using an 11-point (0-10) numerical visual analogue scale immediately after.  The surgeons indicated whether they perceived patient discomfort during 4 different stages of  the operation: opening of the conjunctiva, vitrectomy (if performed), placement of scleral  buckle (if performed) or using the laser probe, and closing of the conjunctiva.  The need for supplemental local anesthesia, and use of IV sedation for additional pain  control intraoperatively were compared between the two groups. Inclusion Criteria:  -  age between 18 and 80 Exclusion Criteria:  -  Uncooperative patients  -  Bleeding disorders  -  High axial length (30mm) with previous buckle surgery

The purpose of this study is to analyze the effect of an interactive parent-child book  reading intervention. The intervention includes two components: the provision of five  children's books to parent-child dyads and information about how to practice interactive book  reading. The investigators expect to find an effect of this intervention on a) infants'  expressive vocabulary, b) reading activity, c) parental expectations and knowledge about  language development and d) parental use of interactive book reading strategies. The foundations of optimal health, growth and development are forged early in life, when  income-related gaps in learning opportunities already exist in Costa Rica. It is therefore  important for the government to mitigate the effects of these gaps through programs targeting  the development of academic, behavioral, socioemotional and economic abilities. Key to the  success of such programs is to consider physical health, nutrition, responsive care and early  learning. Multiple government-led initiatives in Costa Rica had been carried out in order to  provide adequate programs for infants and young children. Evidence of these efforts are  observed in the low rates attained in infant mortality, malnutrition and anemia, as well as  the high coverage of the current immunization program. However, policies targeting early  learning in children under 36 months of age are incipient and government initiatives in this  regard are relatively recent.  The purpose of this study is to promote early language development, a central component of  early learning. Our goal is to implement and evaluate a low-cost intervention targeting  parents of infants who benefit from the existing immunization program of the public health  services offered by the Caja Costarricense del Seguro Social (Costa Rican Social Security  Fund).  The investigators will use an experimental design to randomly assign 15- to 17-month-old  infants and their caregivers to one of two groups: a control group or an experimental group.  In the experimental group, caregivers will receive a package including five children's books  and 36 text messages with information on how to practice interactive book reading with their  children. This information will be delivered over a period of 12 weeks. The control group  will not receive any treatment during the implementation of the intervention.  In order to measure the efficacy of the intervention, the investigators will evaluate a)  infants' expressive vocabulary, b) parent-child reading activity, c) parental expectations  and knowledge about language development and d) parental use of interactive book reading  strategies at baseline (15-17 months of age) and at posttest (18-20 months of age) in the  control and the experimental group. After posttest, the control group will receive the  complete intervention.  The investigators expect to find an effect of the interactive book reading intervention on a)  infants' expressive vocabulary, b) reading activity, c) parental expectations and knowledge  about language development and d) parental use of interactive book reading strategies. Inclusion Criteria:  -  Age limits: 15 months to 17 months.  -  Sex: All.  -  Infant was born full term (≥ 37 weeks).  -  Infant is raised in a monolingual Spanish-speaking home.  -  Mother knows how to read and write.  -  Mother has access to cell phone with internet. Exclusion Criteria:  -  Neither caregivers nor infants must have any significant known physical, mental or  learning disability.

The main goal of this study is to compare the Haemophilus influenzae type b antibody response  in American Indian / Alaska Native (AI/AN) infants to two licensed vaccines: Vaxelis and  PedvaxHIB. Historically, American Indian and Alaska Native (AI/AN) children aged <5 years have  experienced invasive H. influenzae type b (Hib) disease at a rate that is at least 5 times  higher than the general U.S. population. In the pre-vaccine era, the incidence of Hib disease  peaked earlier for AI/AN children at 4-5 months than general US children at 6-9 months.  Therefore, prevention efforts for AI/AN populations focused on identifying a vaccine that  would protect against disease in early infancy. Studies in AI/AN children revealed that the  Hib conjugate vaccine with the capsular polysaccharide (polyribosylribitol phosphate  polysaccharide [PRP]) coupled to the outer membrane protein complex of Neisseria meningitidis  (OMP) induced anti-PRP IgG titers that correlated with protection (GMC ≥0.15 μg/mL) and  demonstrated high efficacy after a single dose in infancy. Hib PRP-OMP was licensed in 1991  as PedvaxHIB; following introduction of a two-dose primary series and a booster dose, the  rate of Hib disease decreased substantially among AI/AN children. The importance of PRP-OMP  vaccine to disease control was highlighted in the 1990s in Alaska when use of a non-PRP OMP  Hib vaccine was associated with an increase in disease incidence in AN children. In 1999, the  American Academy of Pediatrics Committee for Native American Child Health released its  official preference for Hib PRP-OMP for use in AI/AN populations.  In spite of Hib vaccine coverage similar to or greater than the national average, AI/AN  populations periodically experience pediatric cases of invasive Hib disease. In contrast to  the pre-Hib vaccine era, a majority of these cases occur in fully vaccinated children beyond  the first year of life. This epidemiologic shift in the age at which disease occurs may  indicate ongoing transmission in the presence of waning immunity following vaccination.  Vaxelis is a licensed hexavalent combination vaccine that contains Hib PRP-OMP and antigens  (Hepatitis B surface antigen, Diphtheria Toxoid, Tetanus Toxoid, Acellular Pertussis [DTaP],  and Inactivated Polio Virus [IPV]) to protect against diseases caused by 5 other organisms.  Vaxelis contains 3.0 µg/mL of PRP-OMP antigen, compared to 7.5 µg/mL in PedvaxHIB. This lower  concentration of PRP-OMP has been shown to be less reactogenic and similarly immunogenic to  higher doses. Vaxelis is approved for administration as a 3-dose primary series at 2, 4, and  6 months of age. A booster dose with a different licensed Hib vaccine (e.g., PedvaxHIB,  ActHib) is required at 12-15 months. Vaxelis Hib PRP-OMP was found to be highly immunogenic  post-dose 2 at 4 months and post-dose 3 at 6 months. However, immunogenicity post-dose 1 was  not measured in the phase 3 clinical trials of this vaccine.  In June 2019, the CDC's Advisory Committee on Immunization Practices (ACIP) passed a  resolution supporting inclusion of Vaxelis in the Vaccines For Children Program for the  general U.S. population. This vaccine was made available for routine use in the U.S. in 2021.  A preferential recommendation for use of this vaccine in AI/AN children was not given because  post-dose 1 immunogenicity data were not available. To support policy recommendations to  protect the health of the AI/AN community, a study is needed to assess non-inferiority of the  post-dose 1 immune response to Vaxelis compared to the current recommended product  (PedvaxHIB). It is important to demonstrate that infants vaccinated with Vaxelis will be  protected early in life, given the historic early peak of Hib disease and the evidence that  Hib still circulates in village-based and reservation-based AI/AN communities.  If this study finds that Vaxelis and PedvaxHIB provide comparable protection after one dose,  this would support the ACIP making a preferential recommendation for Vaxelis for AI/AN  infants. This would expand the options of preferred vaccines for AI/AN infants and  potentially provide more long-lasting protection given that 3 doses would be given as part of  the primary series.  This study is a prospective, randomized, unblinded, phase IV study of the immunogenicity of  two licensed Hib vaccines among AI/AN infants. The study will enroll approximately 330 AI/AN  infants on Navajo Nation, on White Mountain Apache (WMA) Tribal lands, and in Anchorage,  Alaska who are 6-12 weeks of age and due to receive their first set of routine infant  immunizations. Eligible infants whose parents provide written informed consent will be block  randomized to one of two study arms - either Vaxelis or PedvaxHIB. Participants will make 5  study visits over the course of approximately 5 months. Participants randomized to the  Vaxelis group will receive the vaccination at 2, 4 and 6 months of age, and randomized to the  PedvaxHIB group will receive the vaccination at 2 and 4 months of age.  Four blood samples will be collected: at ages 2, 3, 6, and 7 months. These specimens will be  tested by ELISA to assess anti-PRP antibody levels. Among infants vaccinated at 2 months of  age, the anti-PRP IgG GMC 30 days post dose 1 of Vaxelis will be considered non-inferior if  the ratio of the GMC in the Vaxelis group relative to the PedvaxHIB group is >0.67. The  statistical criterion we are using to define non-inferiority corresponds to the lower bound  of the two-sided 95% confidence interval (CI) on the anti-PRP IgG GMC ratio [Vaxelis /  PedvaxHIB] being >0.67. A sample size of 150 evaluable children per group will provide at  least 80% power to detect non-inferiority using a one-sided two-sample t-test.  Each participant will also be given other routine pediatric immunizations that are not part  of the study regimen, per ACIP schedule and recommendations, (e.g., DTaP and IPV at 2, 4 and  6 months, and hepatitis B vaccine at 2 and 6 months, for participants randomized to  PedvaxHIB; Prevnar13 at 2, 4 and 6 months, and the rotavirus vaccine series at either 2, 4  and 6 months (if given RotaTeq) or 2 and 4 months (if given Rotarix). Inactivated influenza  vaccine will be offered at 6 months of age, as appropriate based on season. Inclusion Criteria:  -  Born at gestational age of ≥35 weeks  -  AI/AN infant between 6 to 12 weeks of age (42-90 days) at the time of the first  vaccination (i.e., Study Day 1)  -  Written informed consent provided by parent(s)/Legally Authorized Representative(s)  (LARs)  -  Investigators believe that the parent(s)/LARs can and will comply with the  requirements of the protocol (i.e., return for follow-up visits, recall of adverse  events)  -  Infant is available to complete the follow-up period of 5 months  -  Healthy infant, as established by medical history and clinical examination before  entering the study Exclusion Criteria:  -  History of receipt of blood, blood products, or immunoglobulin products since birth or  expected receipt through the duration of the study  -  Chronic seizure or evolving or unstable neurologic disorder  -  Congenital Heart Disease, except for uncomplicated CHD (e.g., PDA, small septal  defect)  -  Infant of mother with HIV infection  -  History of reaction or hypersensitivity likely to be exacerbated by any vaccine  component, or to latex  -  Infant with confirmed or suspected immunocompromising medical condition, based on  medical history, including chronic administration (more than 14 days in the lifetime)  of immunosuppressants or other immune-modifying drugs since birth  -  Administration of infant vaccines other than birth dose Hepatitis B, prior to the time  of enrollment  -  Any condition which might interfere with the evaluation of the investigational  product, or interpretation of subject safety or study results, in the opinion of the  investigator  -  Child of an employee of the sponsor, clinical study site, or any other individual  involved with the conduct of the study, or an immediate family member of such  individuals  -  Acute illness and/or fever (temperature ≥100.4 F or ≥38.0 C) at time of enrollment  (Note: Participant with fever may be enrolled at later date if symptoms have resolved  and all other criteria for inclusion are met at that time)  -  Current (or within the past 7 days) or expected receipt of immunosuppressive agents,  including steroids, except topical or inhaled steroids (Note: For oral  corticosteroids, this will mean prednisone (≥ 0.5 mg/kg/day, or equivalent;  participant may be enrolled at a later date if medication use ends and all other  criteria for inclusion are met at that time)

The purpose of this research is to examine the beneficial effects of regular, non-invasive,  glucose (sugar) assessment on glucose (sugar) and blood pressure regulation during pregnancy  to help in predicting gestational diabetes and preeclampsia. This is an open-label pilot trial for the LabClasp combined with standard clinical care  compared to standard clinical on [glucose] and blood pressure during pregnancy. Potential  study participants will be pre-screened using questionnaires and review of their clinical  records. Once the consent has been obtained, participants will undergo screening to confirm  eligibility. Subjects who meet all criteria will be randomized to either LC+SC or SC cohorts  for 24-39wks depending upon their gestational duration at enrollment. Study measures  including anthropometrics, surveys/questionnaires, 24hr ABPM, accelerometry, and an oral  glucose tolerance test (OGTT). Furthermore, the investigators will obtain repeated (annual)  subject information including vitals, labs, medications, and development of cardiometabolic  disorders for up to 10yrs in follow-up by reviewing Mayo Clinic medical records. Inclusion Criteria:  -  • Age range: 18-45 years (inclusive)  -  Body mass index (BMI) ≤40kg/m2  -  >1 risk factor for GDM  -  <16wks gestation  -  Gender: only females will be recruited into this study  -  Target disease or condition: pregnancy  -  Individuals with treated hypertension, prehypertension, and dyslipidemia will be  allowed to participate in the study  -  Ability to provide written informed consent Exclusion Criteria:  -  • Presence of chronic kidney disease (creatinine >2.5mg/dL) and/or active cancer  -  Smoking  -  Multiple pregnancies  -  Congenital abnormalities  -  Use of chronic medications which influence blood [glucose] or [insulin]  -  Subsequent diagnosis of GDM

Adult patients with acute complaints related to the musculoskeletal system are prevalent and  correspond to a large percentage of visits to Emergency Care Units (UPA), often performed by  general practitioners. These patients, in most cases, present complaints associated with  low-complexity trauma, which can be diagnosed through targeted physical examination and  treated with basic guidelines (behavioral/medicinal). The diagnosis of a more complex  fracture or injury requires an assessment by an orthopedist. Currently, patients with  orthopedic complaints are often seen by telemedicine, but there are no studies that have  compared the diagnostic accuracy of remote assessment with standard face-to-face assessment.  Telemedicine is a recognized medical care strategy used for various situations, including as  a virtual emergency service. Despite the current widespread use, there are few studies that  have evaluated the diagnostic accuracy of telemedicine compared to face-to-face evaluation,  and there are no specific studies in patients with orthopedic symptoms. Scientific evidence  of high diagnostic accuracy in telemedicine care can support the investment and expansion of  this modality, expanding and facilitating the access of patients to the health service, with  a reduction in costs and the rational use of resources. The objective of the study is to  analyze the diagnostic accuracy of telemedicine-guided self-examination compared to a  face-to-face medical evaluation at the UPA in adult patients with orthopedic complaints.  Secondary objectives are: evaluation of medical care time, indication of additional tests,  guidance, medical prescription, proposed destination after completion of care, cost and  patient satisfaction. It is a a randomized, prospective, single-center study carried out in  the telemedicine and UPA sectors of Hospital Israelita Albert Einstein. Randomization will be  1:1 and patients will be allocated in the Tele group (evaluation by telemedicine followed by  face-to-face evaluation) or in the Standard group (in-person evaluation). The sample  calculated for non-inferiority was 50 patients in each group. Randomized, prospective, single-center study carried out in the telemedicine sectors and  emergency care unit of Hospital Israelita Albert Einstein, Ibirapuera Unit. The randomization  will be 1:1, from the commercial application Randomizer ®, by the member of the project  Renata Vidigal Correia.  After randomization, patients will be included in one of two possible groups:  1. TELE Group: first care will be provided via telemedicine with a clinical physician,  guiding self-examination guided by telemedicine. After the remote consultation, a  face-to-face evaluation will be carried out with an orthopedist, according to  institutional protocol.  2. GrupoSTANDARD: Face-to-face care with an orthopedist, according to institutional  protocol.  The face-to-face evaluation will be carried out by the local UPA medical and orthopedic care  team and the telemedicine evaluation by the fixed medical team of the HIAE service  responsible for urgency/emergency care.  The study will be of non-inferiority with evaluation of accuracy in both groups, since the  telemedicine group, after completion of care, will pass the face-to-face consultation (gold  standard).  Both in face-to-face and telemedicine assessments, clinical data, final diagnosis,  destination, total time of care, guidance, complementary exams and prescription will be  computed. In the face-to-face evaluation, additional exams and medications received in situ  will also be computed. The final diagnoses will receive nomenclature according to the  International Statistical Classification of Diseases and Related Health Problems - ICD 10  (requirement of institutional records - Cerner) and will be grouped according to the  equivalence of the syndromic diagnosis. The diagnosis of the face-to-face evaluation is made  following institutional protocols based on extensive medical literature and approved by the  institutional clinical staff, being representative of current medical practice and will be  considered the gold standard diagnosis.  The total service time in minutes will be evaluated, verifying if telemedicine can change the  total medical service time. The fee for complementary exams will be counted in the number of  exams requested and their categorization (laboratory exam or imaging exam); the  quantification in number and its categorization (behavioral measures, cryotherapy guidelines  and new medical evaluation if necessary) of the guidelines; categorization of prescription  (only symptomatic or medication in the UPA); destination categorization (high - item valid  for both services, hospitalization - valid item for face-to-face care, search for the ER -  valid item for telemedicine care), hospital cost (measured by the need for  immobilization/complementary tests), and indication of additional tests .  The final diagnosis will be considered by the official report of the radiologist based on the  imaging exams performed. Inclusion Criteria:  -  Age > 18 years;  -  Patient with orthopedic complaints according to the above diagnostic criteria, by the  triage nurse.  -  Signing the informed consent form. Exclusion Criteria:  -  Return to the UPA for maintenance or aggravation of the complaint;  -  Age > 65 years;  -  Patient with emergency room criteria by the evaluation of the triage nursing.  -  Postoperative period of orthopedic surgery < 3 months

Urodynamic study is an invasive procedure and applied for diagnosis of bladder  oversensitivity. Bladder diary is a non-invasive measurement. The aim of this study was to  elucidate whether bladder diary is a good surrogate for diagnosing bladder oversensitivity. Between July 2009 and December 2020, medical records of all women with lower urinary tract  symptoms but without cystocele who visited the urogynecological department of a medical  center for urodynamic evaluation were reviewed. Those women who have no complete data of a  3-day bladder diary were excluded from this study. Bladder oversensitivity was diagnosed if  the volume of strong desire was less than 300mL. We compared the urodynamic parameters to  bladder diary parameters in order to find the best correlation between these 2 measurements  for the diagnosis of bladder oversensitivity.  STATA software was used for statistical analysis. Chi2 test, univariate and multivariable  logistic regression tests were used for statistical analysis as appropriate. A p < 0.05 was  considered as statistically significant. Inclusion Criteria:  -  Women with lower urinary tract symptoms  -  Complete a urodynamic study  -  Complete a 3-day bladder diary Exclusion Criteria:  -  Women with cystocele  -  Chronic infection  -  Incomplete data

This topic foe randomized prospective study.Detection of elderly patients with lunmbar spinal  postoperative inflammatory substances in the blood and drainage of liquid level ,clear  whether low-dose dexamethasone can inhibit the inflammation, the observation of elderly  patients with lumbar spinal postoperative drainage star, to explor whether low-dose  dexamthasone can reduce postoperative incision drainage, thus impove the postoprative  drainage tube pull rate within three days, which in turn reduce because of the place a  retrograde infection caused by drainage tube. A total of 100 patients undergoing posterior lumbar disc fusion were randomly divided into  control group (group C,n=50) and dexamethasone group (group D,n=50). Group D was given  0.15mg/kg dexamethasone (2ml) intravenously after anesthesia induction. Group C was also  intravenously injected with 2ml normal saline after anesthesia induction.On this basis,  monitor the main results and secondary results Inclusion Criteria:  -  Adult patients ≥65years of age  -  American Society of Anesthesiologists (ASA) physical status 2-4  -  Elective or expedited non-cardiac surgery of at least 2 hours dura- tion under general  anaesthesia  -  Requiring a hospital stay of at least one postoperative night  -  A surgical skin incision >5 cm in length or multiple incisions with a total incision  length of >5 cm Exclusion Criteria:  -  Poorly controlled diabetes (HbA1c>9.0%)  -  Endovascular procedure with a small (<5 cm length) skin incision Ophthalmic surgery  -  Planned dexamethasone (or other corticosteroid) therapy (eg, history of intractable  PONV, maxillofacial surgery, intracranial neurosurgery)  -  Recent (<2 weeks since end of treatment) infective episode requir- ing treatment with  antibiotics  -  Chronic antibiotic therapy (eg, for bronchiectasis, cystic fibrosis etc)

This study aims to examine the feasibility and effect of a home-based short-term  telerehabilitation exercise intervention using heart rate monitor and internet platform in  patients with lymphoma. Fifteen lymphoma cancer patients post-treatment (except adjuvant treatment) will be enrolled  in the study. Cardiorespiratory fitness (peak oxygen consumption), adverse events, body  composition and adherence to exercise prescription will be evaluated at baseline, 12-week,  and year after enrollment. Inclusion Criteria:  -  Lymphoma patients post-treatment (except ongoing adjuvant treatment)  -  Post-treatment period not exceeding 3 months  -  Internet connection at home  -  Literacy with information and communication technology  -  Patients who agreed with informed consent Exclusion Criteria:  -  Inability to perform a cardiopulmonary exercise test  -  Psychological severe or cognitive disorders  -  Contraindications for cardiopulmonary exercise testing  -  Other exercise limitations (musculoskeletal disorders)  -  Planned intervention or operation  -  Participants who are enrolled in or participate in other rehabilitation program  -  Participants who plan to be or are included in other studies

Most symptomatic pathologies of the ankle and hindfoot are determined by biomechanical  alterations of this anatomical region. Surgical treatment of these pathologies is therefore  aimed at improving the inferior biomechanical condition, and it can be expected that an  improvement of the biomechanical parameters grossly parallels the targeted clinical  improvement.  3D Multisegment Foot Models have been developed and validated to determine the clinical  outcome. Such a validated 3D Multisegment Foot Model is now standard available in the gaitlab  of UZ Leuven making it possible to study a huge amount of biomechanical parameters within the  foot & ankle region itself. Most symptomatic pathologies of the ankle and hindfoot are determined by biomechanical  alterations of this anatomical region. Surgical treatment of these pathologies is therefore  aimed at improving the inferior biomechanical condition, and it can be expected that an  improvement of the biomechanical parameters grossly parallels the targeted clinical  improvement.  Unfortunately, in the past, biomechanical examination of the lower limb and foot consisted of  two distinct study protocols: gaitlab and plantar pressure measurements.  First, these two study protocols were acquired completely independently. Therefore, it proved  to be very hard to compare the results and get insight in the way altered biomechanics caused  or continued to cause abnormal plantar pressure distributions. However, recently it was  possible to integrate these two modalities, especially concerning the timing of the events,  what makes it possible to reliably link the observed findings.  Second, virtually all gaitlab models considered the foot & ankle region as one single  segment, making it impossible to evaluate any biomechanical parameter within the targeted  region. 3D Multisegment Foot Models have been developed and validated since the beginning of  this century. Such a validated 3D Multisegment Foot Model is now standard available in the  gaitlab of UZ Leuven making it possible to study a huge amount of biomechanical parameters  within the foot & ankle region itself.  Furthermore, only a paucity of information is available if the observed clinical changes are  indeed paralleled by an equally directed biomechanical change.  Historically, all patients at the Foot & Ankle unit of UZ Leuven performed a pre- and 1 year  post-operative plantar pressure measurement to get better insight in their clinical  condition. As stated before, the usefulness of this single testing method was limited.  Recently the Advanced Clinical Examination Platform that integrates both plantar pressure  measurement and full 3D MFM-gaitlab has been implemented in the Movement Analysis Laboratory  of our institution. Currently a transition to routinely perform such an examination is  finished. Therefore a completely new era of research concerning the biomechanical evaluation  itself and clinical results of the reconstructive procedures of ankle and hindfoot has  started. Inclusion Criteria:  -  Being routinely scheduled for a reconstructive surgical procedure for the following  indications or involving the following type of procedure:  1. Any reconstructive procedure for Pes Planus, Pes Plano-valgus, or Posterior  Tibial Tendon Dysfunction  2. Tibio-talar arthrodesis or prosthesis  3. Sub-talar -and/or (partial) Chopart - and/or Triple arthrodesis  4. Pantalar arthrodesis with or without inclusion of the Chopart joint Exclusion Criteria:  -  Age under 18  -  Need of tools (eg walker or crutches) to walk less than 100m  -  Inability to walk less than 100 m anyway  -  Differences in leg length exceeding 3 cm (measured clinically)  -  Extreme in-or outtoeing  -  Subjects with BMI > 27.5 require very careful further consideration whether or not the  obesity prevents the accurate palpation of anatomical landmarks necessary prior to  marker placement. This will be judged on an individual basis.

Malaria remains a major public health concern in Cameroon especially among vulnerable groups  such as children less than five years and pregnant women. Artesunate-amodiaquine (ASAQ) and  artemether-lumefantrine (AL) have been used for the treatment of uncomplicated Plasmodium  falciparum in Cameroon since 2004. Worldwide, several studies among children have reported  high efficacy and safety of artemisinin-based combination therapies (ACTs). There is paucity  of data to support the continuous use of ASAQ and AL in Cameroon. The main objective of this  study is to assess the efficacy and safety of artesunate-amodiaquine and  artemether-lumefantrine during a 28-day follow-up period in children with acute uncomplicated  P. falciparum malaria in the Center Region of Cameroon. A randomized, open-labelled,  controlled clinical trial comparing artesunate-amodiaquine (ASAQ) and artemether-lumefantrine  (AL) will be carried out from 5th April to 31st December, 2021 at six hospitals in the Center  Region of Cameroon. The study participants shall include febrile patients aged 6 months to 10  years with confirmed uncomplicated P. falciparum infection. Eligible children for whom  parent/guardian informed consents are obtained will be randomized to receive either  artesunate-amodiaquine (group A) or artemether-lumefantrine (group B) in the ratio 1:1. A  minimum sample of 76 patients will be required for the study. With a 20 % increase to allow  loss to follow-up and withdrawals during the 28-day follow-up period, 92 patients will be  enrolled for each of the two study arms. The study will recruit a total of 184 patients.  However, since 6 sites will be involved, a minimum of 30 participants shall be enrolled per  site. Drug intake will be done under strict supervision on days 0, 1 and 2. Follow-up visits  will be performed on days 3, 7, 14, 21, and 28 to evaluate clinical and parasitological  resolution of their malaria episode as well as adverse events. Polymerase chain reaction  (PCR) genotyping of merozoite surface proteins 1 and 2 (msp-1, msp-2) as well as glutamate  rich protein (GLURP) will be used to differentiate between recrudescence and new infection. Brief title: Efficacy and safety of artesunate-amodiaquine and artemether-lumefantrine for  the treatment of malaria in Cameroon.  Official title: Monitoring the efficacy and safety of artesunate-amodiaquine and  artemether-lumefantrine for the treatment of uncomplicated Plasmodium falciparum malaria  among children in the Center Region of Cameroon.  Purpose: To monitor the efficacy and safety of artesunate-amodiaquine and  artemether-lumefantrine for the treatment of uncomplicated Plasmodium falciparum malaria  among children in the Center Region of Cameroon.  Background: Malaria remains a major public health concern in Cameroon especially among  vulnerable groups such as children less than 5 years and pregnant women.  artesunate-amodiaquine (ASAQ) and artemether-lumefantrine (AL) are currently being used for  the treatment of uncomplicated Plasmodium falciparum in Cameroon. Worldwide, several studies  among children have reported high efficacy and safety of artemisinin-based combination  therapies (ACTs). There is paucity of data to support the continuous use of ASAQ and AL in  Cameroon.  Objective: To assess the efficacy and safety of artesunate-amodiaquine and  artemether-lumefantrine during a 28-day follow-up period among children with acute  uncomplicated P. falciparum malaria in Center Region of Cameroon.  Study sites: District Hospital Akonolinga, District Hospital Mfou, District Hospital Soa,  District Hospital Mbalmayo, District Hospital Mbandjock, and District Hospital Ngog-Mapubi in  the Center Region of Cameroon.  Study period: 5th April to 31st December, 2021. Study design: This surveillance study is a  two arm, open label, randomized controlled clinical trial.  Patient population: Febrile patients aged 6 months to 10 years, with confirmed uncomplicated  P. falciparum infection. Eligible children for whom parent/guardian informed consents are  obtained will be randomized to receive either artesunate-amodiaquine (group A) or  artemether-lumefantrine (group B) in the ratio 1:1.  Sample size: A minimum sample of 76 patients will be required for the study. With a 20 %  increase to allow loss to follow-up and withdrawals during the 28-day follow-up period, 92  patients will be enrolled for each of the two study arms. The study will recruit a total of  184 patients. At least 30 participants shall be enrolled at each of the six study sites.  Treatment (s) and follow-up: Drug intake will be done under strict supervision on days 0, 1  and 2. Follow-up visits will be performed on days 3, 7, 14, 21, and 28 to evaluate clinical  and parasitological resolution of their malaria episode as well as adverse events. Polymerase  chain reaction (PCR) genotyping of merozoite surface proteins 1 and 2 (msp-1, msp-2) as well  as glutamate rich protein (GLURP) will be used to differentiate between recrudescence and new  infection.  Classification of treatment outcomes: Classification of treatment outcomes will be done based  on the WHO 2009 guidelines: treatment failure (Early Treatment Failure-ETF, Late Clinical  failure-LCF and Late Parasitological Failure-LPF) and treatment success (Adequate Clinical  and Parasitological Response-ACPR). Inclusion Criteria:  -  Children of either gender, aged 6 months to 10 years will be recruited.  -  Uncomplicated P. falciparum malaria confirmed by microscopy using Giemsa-stained thick  film with an asexual parasite density within the range 1000 to 200000 parasites/μl.  -  Presenting with fever (axillary temperature ≥ 37.5oC) or having a history of fever in  the preceding 24 hours.  -  Able to ingest tablets orally (either suspended in water or uncrushed with food).  -  Willing to participate in the study with written informed consent from  parent/guardian.  -  Willing and able to attend the clinic on stipulated regular follow-up visits. Exclusion Criteria:  -  Mixed or mono-infection with another Plasmodium species detected by microscopy.  -  Children who are currently suffering or had the following within the last 2 months:  tuberculosis, HIV, schistosomiasis, diabetes mellitus, cardiovascular disease, gout,  rheumatoid arthritis, underlying chronic hepatic or renal disease, hypoglycaemia,  jaundice, respiratory distress, and other inflammatory-related diseases.  -  Signs/symptoms indicating severe/complicated malaria" according to WHO criteria (WHO  definition) such as:  1. Not able to drink or breastfeed.  2. Persistent vomiting (>2 episodes within the previous 24 hours).  3. Convulsions (>1 episode within the previous 24 hours).  4. Lethargic/unconscious.  5. Severe anemia (hemoglobin < 5 g/dl).  -  Serious gastrointestinal disease.  -  Presence of severe malnutrition defined as a child aged between 6-60 months whose  weight-for-height is below -3 z-score (W/H < 70%) or has symmetrical oedema involving  at least the feet or has a mid-upper arm circumference < 115 mm).  -  Regular medication, which may interfere with anti-malarial pharmacokinetics.  -  History of hypersensitivity reactions or contraindications to any of the medicine (s)  being tested or used as alternative treatment (s).  -  Individuals who have taken part in anti-malarial efficacy and safety studies in the  last 3 months.  -  Participants who have taken anti-malarial drugs within the last one month.

Scientific evidence is growing on the health benefits of herbs/spices. The study is  interested in understanding how various herb and spice blends influence the function of blood  vessels. The study is also interested in how blood sugar, the insulin hormone and immune  cells may be related to how well the blood vessels function. Herbs and spices have components  called phytochemicals that may be related to how well blood vessels function. The study is  planned to investigate these relationships.  After qualifying to participate in the research study, participants will be asked to come to  the Clinical Nutrition Research Center (CNRC) for four on-site Study Days, each lasting for  about 8 hours with a 40 min followup to measure vessels' function the next morning. On each  Study Day, different amounts of herbs/spices will be included in a breakfast meal. The herbs  and spices are purchased in the grocery store and are Italian herbs, cinnamon, and a mix of  pumpkin pie spices (cinnamon, ginger, clove, nutmeg).  All meals will be prepared in the CNRC's kitchen using foods and ingredients purchased at the  local grocery store. Blood collection and blood vessel function tests will be performed  during the Study Day using typical procedures used in hospitals, doctor offices, and clinics. This clinical trial is a single-center randomized, blinded, multi-arm, within subjects, cross  over design and features a repeated postprandial sampling paradigm to evaluate the effects of  herbs/spices on vascular function in individuals who are overweight or moderately obese after  consuming a standardized challenge meal. Subjects will undergo 4 Study Days at least 3 days  apart. On each Study Day subject will receive a standardized meal made with: salt and pepper  only (Control condition) or the same meal with up to 6 gram herbs/spice mix or Italian herb  mix or cinnamon.Each Study Day will last about 8 h with a 40 min follow up the following  morning to complete a 24 h set of procedures. The 24 h assessment allows for assessment of  clinical effects over an extended time frame.  STUDY PROCEDURES:  1. Screening Visit:  Interested subjects will be asked to come to the Clinical Nutrition Research Center  (CNRC) on the IIT (Illinois Tech) Campus, Chicago, IL, where the study will take place  for all in person visits. The screening visit is the first visit and will be used to  determine if an interested person is eligible to participate in the study. The screening  visit will take 2 hours. Prospective subjects must read, sign and date a written  Institutional Review Board approved Informed Consent Form prior to performing any study  procedure. One of our Study investigators will go through the inform consent (ICF) with  subject comprehensively to explain all study related activities as mentioned in the ICF  form.  At the on-site screening visit, subject will be asked to arrive after overnight fasting  for 10-14 hours and be well-hydrated. Subjects will be instructed to drink plenty of  water the 24 hours before the screening visit to ensure they are well hydrated (ie., aim  for intake of at least 8-10 cups over 24 h). They will also be asked to abstain from  vigorous exercise 12 h before the visit. Light activity is acceptable. A series of  procedures will be conducted to determine eligibility to participate in the study,  including venous or capillary blood sampling (by finger prick) to test blood glucose (to  ensure fasting status and inclusion criteria), anthropometric measurements (height,  weight, waist circumference, body composition), Body Mass Index (BMI, calculated from  height and weight) calculation, vital sign measurements (blood pressure and heart rate),  body temperature measurement (by ear thermometer), and completion of a series of  questionnaires relating to their general health and lifestyle. For vital sign  measurements, subjects will sit in a comfortable chair, feet uncrossed and on the floor  and will be asked to rest quietly for 5 minutes before measuring blood pressure and  heart rate. Arm vein will be assessed using a vein access scale test.  Based on the results of fasting blood glucose concentration, the questionnaires, and  health evaluation, subjects who meet the inclusion and none of the exclusion criteria  will be invited to participate in the study.  Subjects who are eligible and accept the invitation to participate will be counseled on  following a limited polyphenolic diet throughout the duration of their participation,  although more strict guidelines will be imposed during the 3 days prior to each study  visit. Shopping lists and meal plans will be provided to subjects, along with counseling  by our staff, to help subjects adhere to the limited polyphenolic diet. Subjects will be  asked not to take any allergy medications and/or any pain medications such as Aspirin,  Excedrin, Ibuprofen (Advil, Motrin, Nuprin), Naproxen, Aleve within 48 hours of each  scheduled study days. Tylenol is allowed. The visit will be rescheduled when  allergy/pain medication is needed within 48 hours prior to study days.  Before leaving the CNRC, subjects will be provided instructions for "How to prepare for  study day", which will include avoidance of vigorous physical activity and alcoholic  beverages, and caffeinated beverages at least 24 hours preceding a Study Day. Usual  coffee and tea can be consumed up to noon time the day before and water encouraged  thereafter. Subjects will also be encouraged to get a usual night of sleep and maintain  usual dietary patterns, except for the guidance provided for limited polyphenol foods  and beverages.  2. Study Day Three days prior to each Study Day, subjects will be instructed NOT to consume  berry containing foods, or dark chocolate and record 3-consecutive days of food intake.  Subjects will be instructed to consume a usual dinner meal the night before the Study  Day and be required to repeat the same dinner and afternoon snacks the night before the  second, third and fourth Study Days.  On each Study Day, subjects will arrive at the clinic after fasting for 10-14 hours and in a  well-hydrated and well-rested state. If they are taking any medication(s) on regular basis,  they will be asked not to take the medication(s) at home and instead bring to the CNRC to be  taken in the presence of the study investigator so the medications(s) is taken at the same  time before each Study Day visit.  On the Study Day, after confirming compliance with the pre-study day procedures,  anthropometric measurements, vital signs (blood pressure, heart rate and ear temperature) and  capillary blood sampling (finger prick, confirmation of fasting state) will be taken. A  licensed healthcare professional (LHCP) will evaluate and place an intravenous catheter at  the antecubital site of subject's arm. An intravenous catheter is a thin flexible tube that  allows sampling of blood through one port throughout the Study Day. Once the catheter is  placed, a baseline blood sample will be taken (Time point t=0).  After completing a baseline blood draw, flow-mediated dilation (FMD) procedure will be  measured. Afterwards, subjects will receive a breakfast meal along with a drink beverage  (Control meal, Control meal +Active-Herbs/Spice mix, or + Italian herbs mix, or +Cinnamon).  The first blood sample will be collected at 0h, with FMD and additional blood samples  conducted/collected at 0.5h, 1 h, 2h, 4h, 5.5h, and 7h. After completion of the 7h blood  collection and FMD procedure, the catheter will be removed and subjects will be evaluated for  safety and/or discomfort/symptoms and they will be given a take-home snack. Subjects will be  asked to return the next morning for completion of 24 h procedures. All dinner and afternoon  snacks consumed on Study Day will be asked to be repeated for future Study Days.  Blood collection: There will be a total of 8 times of blood collection for each Study Day. At  the 0h, 2h, 4h, and 7h time points, blood will be collected a total of 64 milliliters (mL)  (16 mL per each time point) of blood. At the 0.5 h, 1 h, 5.5 h and 24h time points, a total  of 32 mL (8 mL per each time point) of blood will be collected. The total amount of blood  collection per test day 96 mL. . During the whole study, total amount of 384 mL of blood will  be collected which is less than the amount allowed for one time blood donation(550mL). Inclusion Criteria:  -  Body Mass Index between 25 and 35 kg/m2  -  Aged over 18 years old  -  Able to provide informed consent and comply with study procedures  -  Willing to maintain stable body weight and follow his/her habitual diet and physical  activity patterns throughout the trial.  -  People with no documented disease condition that would interfere with the study  endpoints (ie., Cardiovascular disease (CVD), diabetes, hypertension (diagnosed high  blood pressure), major organ diseases) or taking medication or dietary supplements  that may interfere with study endpoints.  -  Judged by the Investigator to be in general good health on the basis of medical  history and screening laboratory tests.  -  Premenopausal women are studied at the same time of the month during the follicular  phase of their menstrual cycle (first 14 days of cycle). Exclusion Criteria:  -  Current smoker and/or marijuana user, past smokers may be allowed in the study if  stopped >2 years  -  Have a history or presence of atherosclerotic cardiovascular disease, inflammatory  disease, diabetes mellitus, or other systemic diseases, psychological or psychiatric  disorders that may interfere with study outcomes  -  Unstable use of any medication/supplement - Have a history of cancer, except for  non-melanoma skin cancer within past 5 years  -  Addicted to drugs and/or alcohol (>4 drinks/day)  -  Have been exposed to any non-registered drug product within last 30 days.  -  Working overnight (e.g. 3rd shift of overnight workers)  -  Have allergies/intolerances to cinnamon, Italian herbs, or other spices or study foods  -  Excessive exercisers or trained athletes  -  Extreme dietary habits (i.e., vegan)  -  Excessive coffee/tea drinker (> 4cups/day)  -  Actively losing weight/ trying to lose weight (unstable body weight fluctuations of >  5 kg in 3 months)  -  Donated blood within last 3 months  -  Female who is pregnant, planning to be pregnant, or breastfeeding  -  The individual has a condition the Investigator believes would interfere with his or  her ability to provide informed consent or comply with the study protocol, or which  might confound the interpretation of the study results or put the person at undue  risk.

The research team will develop a novel training tool to improve finger joint coordination, to  address the unmet need in the current rehabilitation, thereby enhancing hand function and  contributing to improved independence and quality of life for Veterans with stroke. The research team will determine feasibility of training using CA and TA controllers in  subacute stroke. Specifically, we will examine if joint coordination improves over a training  session. The investigators will compare the extent of improvement for each controller and  impairment severity. Inclusion Criteria:  -  Adult Veterans with a stroke 1-6 months ago  -  Ability to move fingers (Chedoke-McMaster Hand Section Stage 2-4) Exclusion Criteria:  -  Inability to follow 2-step commands  -  Severe muscle tone prohibiting proper placement of the fingers (Modified Ashworth  Scale, MAS=5 out of 5)  -  Change in spasticity medication or botulinum toxin injection in the upper limb within  3 months prior to or during enrollment

Antepartum hemorrhage is defined as bleeding from or within the female genital tract,  occurring from 28+0 weeks of pregnancy and till delivery of the fetus. it occurs in 3-5% of  pregnancies and is an important cause of perinatal and maternal morbidity and mortality  worldwide There are many tocolytic agents may have a role in conservative management of placenta previa  such as magnesium sulfate, calcium channel blockers and β-sympathormimetics. In 2004 Sharma  suggests that ritodrine hydrochloride in patients with symptomatic placenta previa tends to  prolong the pregnancy and result in an increase in birth weight of the babies without causing  any adverse effect on the mother and fetus Inclusion Criteria:  -  Estimated gestational age : between 28 weeks and 37 week's gestation  -  Confirmed Placenta previa; either major or minor degrees.  -  Placenta previa with preterm uterine contractions Exclusion Criteria:  -  Severe attack of bleeding requiring an immediate intervention.  -  Fetal heart rates instability or non-reassuring tracing  -  Intrauterine fetal death or major fetal anomalies.  -  If associated with abruptio placentae  -  Patients with known bleeding disorders or on anticoagulant therapy  -  Patients with severe medical disorders as myasthenia gravis documented magnesium  toxicity.

Randomized, multicenter, open-label, Phase 3 registration study designed to evaluate the  safety and efficacy of milademetan compared to trabectedin in patients with unresectable  (i.e., where resection is deemed to cause unacceptable morbidity or mortality) or metastatic  DD liposarcoma that progressed on 1 or more prior systemic therapies, including at least 1  anthracycline-based therapy. Approximately 160 patients will be randomly assigned in a 1:1 ratio to receive milademetan or  trabectedin. Randomization will be stratified by the ECOG performance status (0 or 1) and  number of prior treatments (≤ 2 or > 2) for the patient's liposarcoma.  Patients will receive study drug (i.e., milademetan or trabectedin) until reaching  unequivocal disease progression (RECIST v.1.1) as determined by the Investigator,  experiencing unmanageable toxicity, or until other treatment discontinuation criteria are  met. Patients may be treated beyond tumor progression if they are experiencing clinical  benefit based on the assessment of the Investigator in discussion with the Medical Monitor.  All patients will be followed for documentation of disease progression and survival  information (i.e., date and cause of death) and subsequent treatment information (i.e.,  date/duration of treatment, response, and subsequent disease progression). Long-term  follow-up will continue every 12 weeks (± 7 days) until the endpoint of death, the patient is  lost to follow-up, or for 24 months following the final dose of study drug, whichever comes  first. Inclusion Criteria:  -  Histologically confirmed DD liposarcoma, with or without a WD component (WD/DD  liposarcoma). Note: Patient must be willing to provide an archival tumor tissue sample  that is ≤ 3 years old and of adequate quality or willing to provide a fresh  pretreatment biopsy sample  -  Advanced unresectable (i.e., where resection is deemed to cause unacceptable morbidity  or mortality) and/or metastatic WD/DD liposarcoma  -  Measurable tumor lesion(s) in accordance with RECIST version 1.1  -  Received 1 or more systemic cancer therapy regimens, including at least 1  anthracycline-based regimen, and had radiographic progressive disease (per RECIST  version 1.1) within 6 months before the Screening Visit  -  Resolution of any clinically relevant toxic effects of prior chemotherapy, surgery,  radiotherapy, or hormonal therapy  -  ECOG performance status of 0 or 1  -  Adequate bone marrow function:  -  Platelet count ≥ 100 × 10^9/L  -  Hemoglobin ≥ 9.0 g/dL  -  Absolute neutrophil count ≥ 1.5 × 10^9/L  -  Adequate hepatic function:  -  Alanine aminotransferase and aspartate aminotransferase ≤ 3 × upper limit of  normal (ULN) if no liver metastases are present; ≤ 5 × ULN if liver metastases  are present  -  Total bilirubin ≤ 1.5 × ULN, or ≤ 3 x ULN in the setting of Gilbert's disease Exclusion Criteria:  -  Prior treatment with any mouse double minute 2 (MDM2) inhibitor or trabectedin  -  Other primary malignancies that have required systemic antineoplastic treatment within  the previous 2 years, except for localized cancers that have apparently been cured  -  Gastrointestinal conditions that could affect the absorption of milademetan, in the  opinion of the Investigator  -  Uncontrolled infection within the last 7 days requiring IV antibiotics, antivirals, or  antifungals  -  Known HIV infection or active Hepatitis B or C  -  Untreated brain metastases. Note: Patients who require steroids for brain metastases  must be on a stable or tapering dose of corticosteroids for at least 2 weeks before  randomization. If applicable, patients must complete stereotactic radiosurgery 7 days  before and whole brain radiotherapy 21 days before their first dose of study drug.  -  Investigational therapy administered within the 28 days or 5 half lives:  1. Cytochrome P450 3A4 isozyme strong inhibitor: 5 elimination half-lives  2. CYP3A strong or moderate inducers: 4 weeks  3. Systemic anticancer therapy or investigational therapy 3 weeks or 5 half-lives,  4. Immunotherapy with checkpoint inhibitor: 4 weeks  -  Curative-intent radiation therapy ≤ 4 weeks or palliative radiation therapy,  -  Uncontrolled or significant cardiovascular disease:  1. QTcF at rest, where the mean QTcF interval is > 480 milliseconds  2. Myocardial infarction within 6 months  3. Uncontrolled angina pectoris within 6 months  4. New York Heart Association Class 3 or 4 congestive heart failure  5. Uncontrolled hypertension

The study to evaluate the effect of cyclosporine ( IL2 inhibitor and antiviral) verse  standard care treatment on decrease ADRS, hyper inflammation, hypercytokinemia, and the  mortality rate To test the efficacy of IL-2 inhibitors (Cyclosporine) compared to the Standard of care  according to hospital protocol on COVID-19 patients concerning the clinical outcome  (cytokines level, clinical improvement, and PCR of sARS-CoV-2 through the study period).  AIM:  The slow progression of the disease, improving survival among COVID-19 patients, and Standard  assessment of patient improvement.  -  Standard assessment of patient improvement:  -  PCR-SARS-CoV-2 negative  -  No fever  -  No cytopenia (Hb ≥90 g/L, ANC ≥0.5x109/L, platelets ≥100x109/L) •  -  No hyperferritinemia ≥500 μg/L  -  (Decrease of IL2) Inclusion Criteria:  1. Current infection with COVID-19  2. written informed consent  3. Confirmed diagnosis of COVID-19 by PCR and/or Positive Serology or any existing and  validated diagnostic COVID-19 parameters during this time.  4. 18yrs ≥ Age <66 yrs  5. Chest X-ray showing suggestive of COVID-19 disease.  6. Both gender  7. The presence of Pulmonary fibrosis or hyper inflammation signs or A syndrome of  cytokine release defined as ANY of the following::  1. Leukopenia or lymphopenia,  2. Ferritin > 500ng/mL or D-dimers ≥ 500 ng/mL  3. Hs>90 Exclusion Criteria:  1. Lactation and Pregnancy women  2. unlikely to survive beyond 48h  3. Need for mechanical ventilation.  4. cases of multiorgan failure or abnormal renal function and shock.  5. malignancies, autoimmune disease, Perforation of the bowels or diverticulitis.  6. active bacterial or fungal infection.  7. We define impairment of cardiac function as poorly controlled heart diseases, cardiac  insufficiency, unstable angina pectoris, myocardial infarction within 1 year before  enrollment, supraventricular or ventricular arrhythmia needs treatment or  intervention, Uncontrolled hypertension (>180/110 mmHg.  8. Levels of serum transaminase >5 upper references rang  9. Symptoms of active tuberculosis or human immunodeficiency virus (HIV) positivity  10. the patient receiving Vaccines: Live, attenuated vaccines  11. Subjects received monoclonal antibodies within one week before admission.  12. Patients receiving high-dose systemic steroids (> 20 mg methylprednisolone or  equivalent), immunosuppressant or immunomodulatory drugs  13. Contraindications for use in people with psoriasis include concomitant treatment with  methotrexate, other immunosuppressant agents, coal tar, or radiation therapy.  -

There is lack of evidence on resolution of signs of systemic inflammatory markers by  successful elimination of periapical inflammation by endodontic treatment. Complete blood  count (CBC) may have potential to detect various inflammatory conditions but its use for this  purpose is sparsely reported. To the best of our knowledge effect of chronic apical  periodontitis on various parameters of complete blood count has not been studied. Prevalence of Apical periodontitis (AP) is reported in the range of 17% to 65% with higher  prevalence reported in older patients. Infection of the pulp tissue of the affected tooth is  the principal cause of apical periodontitis and it is characterised by inflammation of the  periradicular tissues. Presentation of AP varies from classical signs of inflammation (pain,  swelling, loss of function) to being completely asymptomatic with only signs of apical bone  resorption on the radiograph. Histological changes seen in AP is localized infiltration of  inflammatory cells and bone resorptions. AP can be treated by root canal treatment (RCT)  which comprises elimination of microbes and their toxic products followed by filling of the  root canal by an inert material. It also acts to limit the spread of microbial infection seen  in AP to jaw and the other parts of the body.  Apical periodontics if left untreated can cause serious complications. Infection and loss of  function caused by loss of teeth may jeopardize overall health of the patients. Chronic  infection like untreated AP may also influence development and progression of other serious  conditions. Numerous inflammatory mediators are responsible for eliciting inflammatory  reactions seen in AP for example both IL-1beta and TNF-alpha are found in periapical lesions  and IL-1beta is suggested to cause greater bone resorption in patients of AP. Role of these  mediators in AP is to cause vasodilation, increased vascular permeability and recruit other  inflammatory cells. It is also been suggested that increased inflammatory mediators seen in  AP may also enhance the systemic inflammation. Inflammation induced tissue damage may vary in  different disease, however the markers that trigger this damage are very similar. They all  act to increase the rate of the inflammatory process, cause tissue destruction and may even  be involved in development of clinical symptoms. For example, markers like hsCRP is  associated with various steps of atherogenesis and is also found elevated in AP. Studies have  reported significantly higher levels of endothelial dysfunction in patients of apical  periodontitis which were found to reduce to normal level following root canal treatment.  A recent systematic review has found significant difference in levels of CRP and IL-6 in AP  subjects than control. IL-6 plays role in initiation of autoimmune disease and chronic  inflammation and also contributes in low grade systemic inflammation. The same systematic  review and meta-analysis has found only eight interventional study that studied effect on  inflammatory marker before and after treatment. The data from these studies were also  heterogenous with wide variety of treatment reported. Only two studies are available which  has evaluated effect of endodontic treatment on levels of isolated groups of inflammatory  mediators and stress markers like reactive oxygen species and circulatory immune complex.  TNF- α is indicated to be responsible for adverse pregnancy outcome and along with CRP may  enhance the insulin resistance. Similarly, complete hemogram indices like mean platelet  volume, neutrophil-lymphocyte ratio is altered in chronic inflammatory conditions and their  estimation could be useful in evaluating overall systemic inflammatory burden of patients of  AP. To the best of our knowledge no study so far has evaluated effect of non-surgical root  canal treatment on the levels of hsCRP and complete hemogram parameters. Therefore, this  study proposes to compare these markers in patients of AP and healthy control and also before  and two years after root canal treatment.  Medical and Dental Examination Prior to treatment a detailed medical and dental history will  be recorded. Oral clinical examinations will include hard and soft tissue evaluation. Pulp  sensibility test will be carried out along with percussion and palpation of the affected  tooth. The periapical radiographic examinations will be carried out at standard exposure  parameters to detect apical bone resorption. Periodontal clinical parameters will be  evaluated at 6 sites in all teeth, including probing depths (PDs), the clinical attachment  level, and bleeding on probing at the base of the crevice, excluding third molars. The  periodontal assessment will be made with a manual periodontal probe (UNC 15; Hu-Friedy,  Chicago, IL).  Blood Samples and Laboratory Analysis Fasting blood samples will be obtained by venipuncture  of the ante-cubital vein. Blood sample will be submitted to the clinical laboratory of the  Department of Biochemistry PGIMS and Department of Oral Pathology, PGIDS, Rohtak, Haryana for  the quantitative analysis of hs-CRP and complete hemogram analysis respectively.  Technique for ELISA: Whole blood sample will be kept at 4°C overnight and centrifuged for 15  minutes at approximately 6000 rpm. Serum will be separated and stored in aliquots at -80 °C  in the until use. Serum hsCRP assay kit will be used. ELISA is a sandwich enzyme immunoassay.  A monoclonal antibody specific for these markers will be pre- coated on the microplate.  Standard and sample will be pipetted into wells and any marker present will be bound by  immobilized antibody. After washing away any unbound substances, enzyme- linked polyclonal  antibody specific for hs-CRP will be added to the wells.  After an incubation period amplifier solution will be added to the wells, and the color will  develop in proportion to the amount of hsCRP bound in the initial stage. The intensity of the  color will be measured.  Root Canal treatment Access opening will be done after rubber dam isolation and  administration of local anesthesia. debridement of the pulp chamber will be done and all  canal orifices will be identified. Negotiation of canals will be done. Working length will be  determined using root ZX apex locator and will be verified radiographically. Coronal  enlargement will be done using Gates- Glidden drills. The apical third of the root canal will  be instrumented up to size 35 for mesial and up to size 45 for distal canals. Finally, root  canals will be further instrumented with step-back technique enlargement in 1 mm increments  to 3 sizes larger than the master apical file. Irrigation will be carried out using 5 mL of a  5% NaOCl solution between files. After preparation, the root canals will be irrigated with 5  mL 17% EDTA for 3 minutes to remove smear layer, followed by 5 mL 5% NaOCl. The final  irrigation will be done with 5 mL distilled water. The root canals will be dried using paper  points and filled with laterally condensed gutta-percha (Dentsply Maillefer) and Zinc oxide  Eugenol based sealer mixed according to manufacturers' instructions. Gutta- percha will be  cut with a heated instrument and vertically condensed right at the orifice opening of the  canals. Final composite resin restoration will be done following manufacturer instruction.  Follow up Follow up and clinical and radiographic examination will be carried out at six  months. Re-assessment of hs-CRP and complete hemogram indices will also be done of all  patients at 6 months Inclusion Criteria:  -  Pulpal necrosis in mature mandibular molar as confirmed by negative response to pulp  sensibility test (cold and electric pulp test)  -  Radiographic evidence of apical periodontitis in the form of periapical radiolucency  -  Radiographic alveolar bone breakdown not more than one third of root length. Exclusion Criteria:  -  Obese (BMI >30 kg/m2), smoker, pregnant, diabetic, immunocompromised or have any other  systemic inflammatory condition.  -  Having a positive history of antibiotic use within the past month or require  antibiotic premedication for dental treatment (including infective endocarditis or  prosthetic joint prophylaxis).  -  Teeth having previous root fillings, unrestorable teeth, fractured/perforated roots,  grade 3 mobility, and history of recent periodontal therapy (within previous 6  months).  -  Teeth with established endodontic-periodontal lesions exhibiting <2 mm radiopaque bone  between the root apex.

The PERHAPS project aims to fill two gaps in the scientific literature: on the one hand,  studying the clinical and cognitive particularities of poker-related problems, and on the  other hand, studying poker skill as a combination of multiple cognitive and emotional  abilities. The underlying clinical aim is to develop a cognitive remediation therapy program  dedicated to pathological gamblers. In the literature, although compulsive poker players undoubtedly share similarities with the  compulsive gamblers of other gambling games, clinicians have observed significant  specificities in these patients, in terms of personality profile, gaming practices and  associated troubles. These specificities could influence the effectiveness of treatment and  prevention strategies in many ways. However, there are very few studies focused on the  specific poker-related problems, particularly compared to other practices.  Furthermore, skill at poker has often been treated as a unique and general ability. This  binary vision is now considered widely insufficient and most researchers recommend exploring  the individual cognitive abilities at play in poker skill. To the investigators knowledge, no  study has done this to date.  Consequently, the PERHAPS project aims to fill two gaps in the scientific literature: on the  one hand, studying the clinical and cognitive particularities of poker-related problems, and  on the other hand, studying poker skill as a combination of multiple cognitive and emotional  abilities.  Three profiles of poker players will be studied, depending on their gambling practices and  whether or not they are addicted: a control group of 30 non-poker players, a group of 30  expert unproblematic poker players, and a group of 30 pathological poker players.  The three groups will be compared with one another on:  -  Cognitive and emotional abilities (for expert players) or deficits (for pathological  gamblers)  -  Clinical particularities of poker-related problems  Secondarily (ancillary study), pathological poker gamblers will be compared with pathological  gamblers of other gambling games (pure chance games n=30 and quasi-skill games n=30).  The PERHAPS project aims to improve knowledge of gambling addiction, particularly as regards  poker, in order to optimise prevention and care strategies. The clinical aim is especially to  construct a cognitive remediation therapy program. It also intends to discuss the legal  framework applied to poker under the gambling regulation. Inclusion Criteria:  -  18-59 years  -  good understanding of French, literate  -  correct level of vision and hearing  -  specific inclusion criteria for each group include frequency and length of poker  practice, DSM-5 doagnostic criteria for gambling disorder Exclusion Criteria:  -  protected adults  -  important cognitive deficit (assessed by the MMSE)  -  psychotic syndrome whole life  -  other psychiatric disorders (mood disorders, anxiety disorders) and addictive  disorders (disorders related to the use of alcoholic or other substances, excluding  nicotine) that are present and not stabilized  -  unstable endocrine disorders  -  significant neurological disorders (such as head injuries (except mild),  neurodegenerative diseases, unbalanced epilepsy, mental retardation, etc.)  -  psychoactive use (before participation)  -  color blindness  -  cardiac disorders  -  electronic implants

The objective of this study is to compare the difference in daily protein intake of  critically ill patients in two standardized enteral nutrition formulas (20% versus 33%  percent) with the same caloric density of 1.2 kcal/ml.  The total amount of protein taken in on day four after starting the early enteral feeding is  defined as primary endpoint. For years, the Surgical Intensive Care Unit of the University Hospital Basel has used an  early enteral approach for the feeding of critically ill patients with different formulas  that have high protein content (20% of total energy). However, the energy goal in the first  week is only 20 kcal for normal-weight and 12.5 kcal for obese patients, which results in  daily protein amounts of 0.8 to 1 g/kg bodyweight (BW), so that additional protein has to be  administered. Due to a suggestion of the dietetic service of the University Hospital Basel,  Fresenius Kabi produced a whey based enteral feeding formula for intensive care patients.  Specific further adaptations for this patient group included micronutrients and a fatty acid  profile as well as low fibres. Surgical Intensive Care Unit of the University Hospital Basel  now are offered the opportunity to test this formula in clinical practice and hypothesize  that this specific high-protein (30% of energy) enteral formula reaches the same amount of  daily caloric intake with a higher total daily amount of protein and equal intestinal  tolerance compared to a usual intestinal nutritional formula.  In order to test this hypothesis, investigators plan a double-blind, randomized and  controlled study with the aim to achieve a target protein quantity of ≥1.3 g/kg BW with an  energy target of 20kcal/kg BW per day, based on a new, specifically designed formula for  critically ill patients. The amount of protein on day four after starting the early enteral  feeding is defined as primary endpoint. Secondary endpoints are the total amount of calories,  the nitrogen balance on day five as well as side effects like gastric residual content,  diarrhoea and constipation. Inclusion criteria were an expected stay at the ICU of four days  or longer on admission and 18 years of age or older Exclusion criteria consisted of BMI ≤ 18,  pregnancy, intestinal perforation, mechanical intestinal obstruction, terminal state of  consuming disease, severely impaired liver function and noradrenaline ≥0.5µg/kg BW/min.. On  this purpose, 90 critically ill patients will get either of the two enteral feeding products  as described above. In case of the event that an increased protein intake can be obtained by  the protein-rich formula, an additional study will investigate the influence of early  protein-rich nutrition on skeletal muscle wasting with critically ill patients.  In a pre-study investigators will administer the high protein formula to 20 patients to test  tolerance and suitability for the nutritional Targets in question. Tolerance will be defined  by the absence of one of the following clinical symptoms :  -  Reflux  -  Diarrhoea  -  Constipation  -  Nausea  -  Vomiting Inclusion Criteria:  -  Adult patients (age 18 years or older)  -  expected stay at the ICU of four days upon admittance or longer  -  expected enteral feeding during at least four days. Exclusion Criteria:  -  BMI ≤ 18  -  Mechanical intestinal obstruction  -  Intestinal perforation  -  Severely impaired liver function  -  Terminal state of consuming disease  -  Noradrenaline ≥0.5µg/kg BW/min  -  Pregnancy

Will participants with painful lower extremity diabetic peripheral neuropathy (DPN) that are  treated with high frequency spinal cord stimulation (HF10 SCS) have improvements in lower  extremity peripheral nerve function? This research study is being conducted to find out if spinal cord stimulation (SCS) can  improve nerve function. SCS is FDA approved for the treatment of intractable neuropathic  (nerve) pain related to diabetic peripheral neuropathy. With SCS a wire is placed in the  epidural space and the spinal cord is stimulated to interrupt the pain signal coming from the  legs. The spinal cord stimulator is a device similar to a pacemaker (which helps treat  abnormal rhythms of the heart). Recent studies have suggested that SCS with high frequencies  can improve nerve function for subjects with painful peripheral neuropathy therefore, the  investigators are looking to measure changes in nerve function after SCS for treatment of  painful diabetic peripheral neuropathy.  The purpose of this research is to gather information on the effect of high frequency spinal  cord stimulation (HF10) on nerve function with a spinal cord stimulator. Inclusion Criteria:  -  Type 2 diabetes mellitus  -  Refractory predominantly lower extremity neuropathic pain for > 1 year  -  Presence of length dependent peripheral neuropathy on sudomotor testing  -  Completed spinal cord stimulation trial with 40% or greater pain reduction from  baseline  -  Failed medication trials or contraindication to gabapentin medications (gabapentin,  pregabalin) and/or serotonin/norepinephrine reuptake inhibitors (tricyclic  antidepressant (TCA) or duloxetine or venlafaxine)  -  Average pain score on a visual analog scale (VAS) of ≥ 5 (with 0 representing no pain  and 10 the worst pain imaginable)  -  Appropriate surgical candidate for spinal cord stimulator Exclusion Criteria:  -  Severe Autonomic Neuropathy as measured by the composite autonomic scoring scale (10  point scale) with a score ≥ 7  -  History of sympathectomy  -  Uncontrolled arterial hypertension (Systolic Blood Pressure >160)  -  Baseline Foot TcPO2 < 10 mmHg to exclude patients with severe peripheral arterial  disease  -  Hemoglobin A1c > 8%  -  Stable opioid regimen with oral morphine equivalent ≥ 100 mg/day  -  Alternative principle cause for peripheral neuropathy or lower extremity neuropathic  pain  -  Disruptive psychiatric disorder (screened for during preoperative psychiatric  evaluation)  -  Pending litigations  -  Women of child bearing potential unwilling to use contraception or found to be  pregnant as part of perioperative screening  -  Patients unable to hold medications that would impact autonomic testing

This study investigates the potential curative properties of gamma delta T-cells obtained  from a blood-related donor of an AML patient. This is an open-label, safety and efficacy, escalating dose, single arm study on 9 adult  subjects (3 cohorts) and 3+3 design will be used. HLA typed patients and potential  blood-related donors will be screened for comorbidities. Suitably matched or haploidentical  family donors will be selected according to protocol specified criteria and institutional  guidelines of participating site. Inclusion Criteria:  1. History of acute myeloid leukaemia (initially diagnosed by presence of 20% or more  blast cells with myeloid or monocytic differentiation confirmed by flow cytometry in  peripheral blood or bone marrow)  2. Relapsed or refractory AML  1. AML relapse after intensive chemotherapy OR  2. AML relapse after allogeneic HCT OR  3. AML progression on low intensity therapy (low dose cytarabine, 5-azacytidine or  decitabine) OR  4. No response to at least 4 cycles of low intensity therapy  5. AML refractory to 2 cycles of induction chemotherapy  3. Presence of > 5% of blasts in bone marrow or peripheral blood smear  4. Patient not eligible for or does not consent to high dose salvage chemotherapy and/or  allogeneic Haematopoietic Cell Transplantation (HCT)  5. Considered suitable for lymphodepleting chemotherapy  6. Age 18 years up to the age of 70 (≤ 70)  7. Life expectancy of at least 3 months  8. Karnofsky performance status ≥ 50%  9. Available related HLA-haploidentical or HLA-matched donor  10. Ability to be off systemic prednisone and other immunosuppressive drugs for at least 3  days prior to γδ T cells product infusion. Maintenance replacement steroid is allowed.  11. Patient able to understand and sign written informed consent Exclusion Criteria:  1. Uncontrolled infections  2. Renal insufficiency: creatinine > 180 μmol/L or on dialysis  3. Heart failure: EF < 40%  4. Respiratory insufficiency: oxygen therapy required at inclusion in the study  5. Significant liver impairment: bilirubin > 50 μmol/L, AST or ALT > 4 times normal upper  limit  6. Treatment with bisphosphonates (2 months before start)  7. Active autoimmune disease or GvHD  8. Pregnant or breastfeeding  9. Patient of fertile age not using two-barrier method of birth control.

This research study is being done to learn if the study drug belantamab mafodotin, in  combination with other standard medications, can improve multiple myeloma. This study will  also help determine what effects, good and/or bad, this combination of study drugs have on  subjects and their cancer, and to evaluate the overall response to this study treatment  combination. This is a phase I dose escalation and expansion study in RMM and RRMM followed by a single  arm phase II expansion in high risk, NDMM. The phase I portion of the protocol will utilize a  standard 3+3 dose escalation design to determine the maximum tolerated dose (MTD) and RP2D of  the KRd-belantamab mafodotin combination. The phase II portion of the trial is a two-stage  design that will assess the efficacy and safety of the combination in newly diagnosed,  high-risk MM patients. Inclusion Criteria:  1. Written informed consent and HIPAA authorization for release of personal health  information signed by the subject or his/her legally authorized representative. NOTE:  HIPAA authorization may be included in the informed consent or obtained separately.  2. Age greater than or equal to 18 years at the time of consent. Because no dosing or  adverse event data are currently available on the use of belantamab mafodotin as a  single agent or in combination with KRd in subjects less than 18 years of age,  children are excluded from this study.  3. ECOG Performance Status of less than or equal to 2  4. Demonstrate adequate organ function  5. Adequate cardiac function as defined by a greater than 40% left ventricular ejection  fraction (LVEF) by ECHO, cardiac MRI or MUGA  1. Note for subjects in phase II: if a cycle of pre-study induction therapy  containing a PI or anthracycline was administered, assessment of the LVEF must be  repeated.  6. For those with symptomatic pulmonary disease with Grade 2 or higher symptoms (e.g.  COPD, asthma) or other signs / symptoms of pulmonary disease, adequate pulmonary  function as defined by a FEV1 greater than or equal to 50% of predicted and DLCO/VA  greater than or equal to 50% of predicted  7. Females of childbearing potential (FCBP) must have two negative serum pregnancy tests  during screening: the first within 10-14 days prior to first dose of study treatment  and the second within 24 hours prior to first dose of study treatment. NOTE: Females  are considered of childbearing potential unless they are surgically sterile (have  undergone a hysterectomy, bilateral tubal ligation, or bilateral oophorectomy), are  amenorrhoeic for less than 2 years without history of a hysterectomy and oophorectomy  must have a follicle stimulating hormone value in the postmenopausal range upon  screening evaluation; or are postmenopausal (at least 12 consecutive months with no  menses without an alternative medical cause).  8. FCBP must be willing to use 2 effective contraceptive methods (at least one that is  highly effective) or abstinence starting from the time of informed consent, while on  belantamab mafodotin and lenalidomide. If either drug is discontinued, 2 effective  forms of contraception should be continued until at least 4 weeks after the last dose  of lenalidomide, and 1 form of effective contraception should be continued until 4  months post last dose of belantamab mafodotin. FCBP should use effective contraception  or abstinence from consent until 30 days after last treatment with carfilzomib, and  males with a partner of childbearing potential must use effective contraception or  abstinence for at least 90 days post last dose of carfilzomib.  9. Male subjects must agree to the following from the first dose of study treatment until  6 months after the last dose of belantamab mafodotin, to allow for clearance of  altered sperm:  1. Refrain from donating sperm  PLUS either:  2. Be abstinent from heterosexual intercourse as their preferred and usual lifestyle  (abstinent on a long term and persistent basis) and agree to remain abstinent. OR  3. Must agree to use effective contraception/barrier as detailed below:  Agree to use a male condom, even if they have undergone a successful vasectomy, and female  partner of reproductive potential to use an additional highly effective contraceptive  method with a failure rate of less than 1% per year 10. FCBP must agree not to donate eggs  (ova, oocytes) for the purpose of reproduction during the intervention period and for at  least 4 months after the last dose of study intervention belantamab mafodotin, at least 30  days after the last dose of carfilzomib, and at least 4 weeks after the last dose of  lenalidomide.  11. As determined by the enrolling physician, ability of the subject to understand and  adhere with study procedures for the entire length of the study 12. Ability to swallow oral  medications 13. Willing to refrain from using contact lenses while participating in this  study  1. Subjects with Relapsed or Relapsed/Refractory MM who have had 1-3 lines of prior  therapy.  a. Refractory is defined as less than 25% reduction in M-protein or progression of  disease during treatment or within 60 days after cessation of treatment b. A line of  therapy is defined as one or more cycles of a planned treatment program.  This may consist of one or more planned cycles of single-agent therapy or combination  therapy, as well as a sequence of treatments administered in a planned manner. A new  line of therapy starts when a planned course of therapy is modified to include other  treatment agents (alone or in combination) as a result of disease progression,  relapse, or toxicity. A new line of therapy also starts when a planned period of  observation off therapy is interrupted by a need for additional treatment for the  disease.  2. Subjects must have measurable disease, as defined by at least one of the following:  a. Serum monoclonal protein level greater than or equal to 0.5 g/dL b. 24-hour urinary  M-protein greater than or equal to 200 mg c. Involved free light chain level greater  than or equal to 10 mg/dL, along with an abnormal free light chain ratio.  3. Subject must have not progressed on full dose lenalidomide previously (25 mg on days  1-21 of a 28-day cycle or its dosing equivalent based on renal function at the time of  progression)  4. Prior to enrollment:  a. There should be a washout period of ≥14 days from any prior chemotherapy AND b. The  subject must have adequate recovery from toxicity of prior chemotherapy as defined by  the following: i. Hematologic lab results within parameters noted in Table 3.2.1 ii.  Non-hematologic toxicity resolved to grade 1 or baseline with the following  exceptions:  1. Subjects who have started a course of antibiotic therapy for infection and symptoms  have improved to baseline or grade 1, but remain on antibiotic therapy are eligible  2. Subjects with ≤grade 2 fatigue are eligible  3. Subjects with ≤grade 2 hyperglycemia are eligible, even if pharmacologic treatment was  required  4. Subjects with ≤grade 2 electrolyte abnormalities are eligible, even if pharmacologic  treatment was required  5. Subjects with ≤grade 2 nausea, constipation or diarrhea are eligible, even if  pharmacologic treatment was required  1. Active, newly diagnosed multiple myeloma with CRAB features or a myeloma-defining event  per the IMWG 2014 criteria. Note: It is acceptable to include subjects who have had one  cycle of emergent treatment for multiple myeloma.  2. High-risk disease, as defined by at least one of the following: i. Del(1p) ii. Gain of  1q21 [greater than or equal to 3 copies] iii. Monosomy 13 or del(13q) by conventional  karyotype iv. High risk IgH translocation [t(4;14), t(14;16) or t(14;20)] v. del(17p) 3.  Measurable disease by 1 or more of the following:  1. Serum monoclonal protein level greater than or equal to 0.5 g/dL  2. 24-hour urinary M-protein greater than or equal to 200 mg  3. Involved free light chain level greater than or equal to 10 mg/dL (100 mg/L), along  with an abnormal free light chain ratio.  4. Note: for subjects who have received a prior cycle of non-protocol therapy, measurable  disease will be based on the serum and urine monoclonal protein and serum free light  chain levels prior to the cycle of non-protocol therapy 4. No more than one prior  cycle of non-protocol therapy will be allowed, recognizing that high-risk multiple  myeloma subjects frequently require immediate therapy at initial diagnosis even before  risk assessment is complete. For those subjects who receive a cycle of non-protocol  induction therapy:  a. There should be a washout period of ≥14 days from the last dose of pre-study therapy AND  b. The subject must have adequate recovery from toxicity of pre-study therapy as defined by  the following: i. Hematologic lab results within parameters ii. Non-hematologic toxicity  resolved to grade 1 or baseline with the following exceptions:  1. Subjects who have started a course of antibiotic therapy for infection and symptoms  have improved to baseline or grade 1, but remain on antibiotic therapy are eligible  2. Subjects with less than or equal to grade 2 fatigue are eligible  3. Subjects with less than or equal to grade 2 hyperglycemia are eligible, even if  pharmacologic treatment was required  4. Subjects with less than or equal to grade 2 electrolyte abnormalities are eligible,  even if pharmacologic treatment was required  5. Subjects with less than or equal to grade 2 nausea, constipation or diarrhea are  eligible, even if pharmacologic treatment was required Exclusion Criteria:  1. Active infection requiring systemic therapy. NOTE: at the discretion of the treating  investigator, subjects who have started antibiotic therapy for subjects who had  symptoms present, symptoms must have improved to baseline or grade 1 in severity may  start treatment prior to completion of their course of antibiotic therapy.  2. Pregnant or breastfeeding (NOTE: breast milk cannot be stored for future use while the  mother is being treated on study.)  3. Subjects cannot have other prior or concomitant malignancies except for:  1. Curatively treated non-melanoma skin cancer  2. Other cancer for which the subject has been medically stable for at least 2 years  and/or, in the opinion of the Site Principal Investigators, will not affect the  evaluation of the effects of clinical trial treatments on the currently targeted  malignancy  4. Active central nervous system (CNS) involvement  5. Concomitant AL amyloidosis or POEMS syndrome  6. Plasma cell leukemia  7. Treatment with any investigational drug within 14 days or five half-lives, whichever  is shorter, prior to first dose of study treatment.  8. Medical, psychiatric, or other condition/disorder (including lab abnormalities) which,  in the opinion of the treating physician, would make this protocol treatment  unreasonably hazardous for the subject, or could interfere with obtaining informed  consent or compliance to the study procedures  9. Significant cardiac disease, including any of the following:  1. Greater than or equal to Class 3 New York Heart Association (NYHA) congestive  heart failure (see Appendix B)  2. ECG evidence of acute ischemia  3. Unstable angina  4. Myocardial infarction, Coronary angioplasty, stenting, or bypass grafting within  three months prior to day 1 of treatment  5. Clinically significant uncontrolled and/or untreated arrhythmias or conduction  block, including clinically significant ECG abnormalities such as 2nd degree  Mobitz Type ll or 3rd degree atrioventricular (AV)block. However, PACs, PVCs,  rate controlled atrial fibrillation, sinus arrhythmia, asymptomatic sinus  bradycardia or sinus tachycardia and 1st degree heart block are not considered  clinically significant.  6. Greater than or equal to Grade 2 QTcF prolongation (i.e. >480 msec)  10. Uncontrolled hypertension, defined as a systolic blood pressure of greater than or  equal to 160 mmHg or a diastolic blood pressure of greater than or equal to 90 mmHg  11. Grade greater than or equal to 2 peripheral neuropathy  12. Psychiatric illness/social situation that would limit compliance with study  requirements as determined by the investigator  13. Known immediate or delayed hypersensitivity or allergic reaction to any components of,  or related to, protocol therapy (e.g. during exposure to carfilzomib, lenalidomide or  dexamethasone as part of a pre-study cycle of therapy).  14. History of erythema multiforme to lenalidomide or other IMID  15. Discontinuation of prior carfilzomib, lenalidomide or dexamethasone due to treatment  toxicity  16. Major surgery within 4 weeks prior to day 1 of treatment  17. Radiation within 14 days prior to day 1 of treatment. Note: palliative XRT to less  than 5% of the total marrow volume as assessed by the treating investigator is allowed  within 14 days prior to day 1 of treatment  18. Current corneal epithelial disease except mild changes in corneal epithelium  19. Positive hepatitis C antibody test result (this test preferable) or positive hepatitis  C RNA test result at screening or within 3 months prior to first dose of study  treatment  a. NOTE: Subjects with positive Hepatitis C antibody due to prior eradicated disease  can be enrolled if a confirmatory negative Hepatitis C RNA test is obtained  20. A known diagnosis of HIV  21. Is seropositive for hepatitis B (defined by a positive test for hepatitis B surface  antigen [HBsAg]). Subjects with resolved infection (i.e. subjects who are HBsAg  negative but positive for antibodies to hepatitis B core antigen [anti-HBc] and/or  antibodies to hepatitis B surface antigen [anti-HBs]) must be screened using real-time  polymerase chain reaction (PCR) measurement of hepatitis B virus (HBV) DNA levels.  Subjects who are PCR positive will be excluded. Subjects with Hepatitis B surface  antibodies and previous Hepatitis B vaccination will be eligible.  22. Has current unstable liver or biliary disease defined by the presence of ascites,  encephalopathy, coagulopathy, hypoalbuminemia, esophageal or gastric varices,  persistent jaundice, or cirrhosis. Note: Stable non-cirrhotic chronic liver disease  (including Gilbert's syndrome or asymptomatic gallstones) or hepatobiliary involvement  of malignancy is acceptable if otherwise meets entry criteria  23. Participant must not have presence of active renal condition (infection, requirement  for dialysis or any other condition that could affect participant's safety).  Participants with isolated proteinuria resulting from MM are eligible, provided they  fulfill inclusion criteria  24. Participant must not have had plasmapheresis within 7 days prior to first dose of  study treatment  25. Any evidence of active mucosal or internal bleeding  26. Participant must not be simultaneously enrolled in any therapeutic clinical trial  27. Administration of live or live-attenuated vaccines within 30 days prior to the first  dose of study treatment

This is a Phase 3, randomized, placebo-controlled, double masked, parallel design study in  healthy subjects performed in the US. It is designed to evaluate the safety and anesthetic  efficacy of AG-920 Sterile Topical Ophthalmic Solution. This is a Phase 3, randomized, placebo-controlled, double masked, parallel design study in  healthy subjects performed in the US. It is designed to evaluate the safety and anesthetic  efficacy of AG-920 Sterile Topical Ophthalmic Solution. In this study, subjects who provide  informed consent and fulfill all the inclusion criteria and none of the exclusion criteria  will be randomized in a 1:1 ratio to receive a single dose of AG-920 or identical looking  placebo into the study eye. Subjects will undergo a conjunctival pinch procedure and the pain  associated with the pinch rated. Inclusion Criteria:  1. Provide written informed consent prior to any study-related procedures being  performed.  2. Is male or a non-pregnant, non-lactating female aged 18 years or older.  3. Willing and able to follow instructions and be present for the required study visits.  4. Have an Early Treatment Diabetic Retinopathy Study (ETDRS) Best Correct Visual Acuity  (BCVA) of 20/200 or better in each eye.  5. Have an Intraocular Pressure (IOP) between 7 and 30 mmHg.  6. Certified as healthy by clinical assessment.  7. Verbal communication skills adequate to participate.  8. Able to tolerate bilateral instillation of Over-The-Counter artificial tear product  based on investigator judgement. Exclusion Criteria:  1. Have participated in an investigational study within the past 30 days.  2. Have a contraindication to local anesthetics.  3. Have known decreased corneal or conjunctival sensitivity.  4. Have had ocular surgery in either eye within the past 90 days.  5. Have had an intravitreal injection in either eye within 14 days.  6. Have ocular disease requiring punctual plugs or ocular inflammation.  7. Are currently using a systemic opioid or opiate analgesic or topical NSAID.  8. Cannot withhold their over the counter (OTC) artificial tear lubricant products for  one hour preceding or following study medication.  9. Any condition, including alcohol or drug dependency, that would limit the subject's  ability to comply with the procedures of the protocol.

Knee osteoarthritis (KOA) is one of the most common and disabling conditions among Veterans.  Management of KOA is challenging as there are few effective treatments other than joint  replacement. Importantly, low levels of physical activity in patients with knee problems  might worsen pain and disability. This study aims to determine the feasibility of using  methods to change behavior that use social incentives and promote physical activity through  playing games and interacting with a web-based platform. The study will also evaluate an  important and widely used treatment, namely corticosteroid injections. Participants will be  randomized into one of 4 arms and will receive a different combination of social incentives  and injections. The study will evaluate which approach is most effective at promoting  physical activity and reducing pain and disability. Knee osteoarthritis (KOA) is one of the most prevalent and disabling conditions among  Veterans and accounts for high morbidity and high costs for the VA. Management of KOA is  challenging as there are few consistently effective treatments other than joint replacement.  Importantly, chronic reductions in physical activity in patients with KOA may worsen pain,  physical function, and exacerbate the metabolic consequences of obesity. Moreover, the  greater mortality observed in symptomatic knee OA populations is likely mediated through its  effect on physical activity. The current proposal aims to derive preliminary data to support  a large pragmatic trial testing the impact of interventions geared towards improving physical  activity and function in KOA patients.  Promoting physical activity has been shown to be helpful in reducing pain and improving  function in KOA and other groups. However, promoting behavioral change in the arthritis  population is a significant challenge. The group has shown that social incentives [and  gamification] derived from concepts from the field of behavioral economics to promote  behavioral change and increase physical activity can be both practical and effective in other  settings. The investigators' group is studying incentives in patients with inflammatory  arthritis with the goal of addressing fatigue, pain, and deficits in physical function. The  incentivization of physical activity using this approach represents a novel intervention for  the managing symptoms of KOA and to improving overall health.  Analgesic therapies can help KOA patients participate in exercise therapy. However, whether  corticosteroid injections, a commonly used medical therapy for KOA pain, has a positive  impact of physical activity is unknown and is an additional important question addressed by  the current proposal. Despite widespread use, definitive data demonstrating a consistent  benefit of corticosteroids are lacking. A large randomized trial recently tested the effects  of repeated corticosteroids injections every 3 months for a period of 2 years on patient  reported pain as well as progression of disease measured by magnetic resonance imaging (MRI).  This study demonstrated no improvement in pain compared to saline injections. In addition, a  small but statistically significant decline in cartilage thickness on MRI was observed,  raising a concern for side effects. These recent data might suggest that corticosteroid  injections result in more harm than good, and may discourage providers from performing this  intervention. However, there are critical weaknesses to this study. Pain and function were  only assessed at 3-month intervals, while previous trials have suggested that peak benefit is  expected at 4-8 weeks. Moreover, the clinical and biologic significance decrease in cartilage  thickness is unclear.  The investigators propose to fill these important knowledge gaps with an innovative and  efficient pragmatic clinical trial with a factorial and crossover design. A large and  definitive practical trial would lead to better understanding of the clinical effectiveness  of these interventions, the meaningfulness of their combined impact, and the subgroups that  are most likely to derive benefit. This clinical trial of 32-40 patients will leverage unique  resources available through the Penn Center for Innovation to better capture important  patient-reported outcomes in real-time through a web-based platform. The study will also test  the feasibility of a crossover and factorial design to improve efficiency and reduce  confounding. Each patient will receive each intervention (saline, corticosteroids) in random  order over 1 year. A factorial design will be employed and will randomize participants to  receive social incentives with gamification to promote increases in their physical activity.  To accomplish these aims, the investigators will utilize innovative mobile applications for  smart phones and wearable activity trackers through the Way-to-Health platform and assess, in  real time, the impact of the intervention on patient-reported function and pain as well as  physical activity. The technology will allow for the recording of outcomes as they occur,  between clinic visits, thereby avoiding information bias due to poor recall. It will also  provide real-time assessment of symptoms, providing granular assessments of response over  time. The investigative team includes early career investigators with experience conducting  similar trials using this infrastructure. Results will provide preliminary data to power a  large, feasible, and low-cost pragmatic multi-site trial that would lead to practical  implementation. The specific aims of the study are:  Aim 1: To determine the feasibility of recruitment and retention of Veterans with  osteoarthritis of the knee (KOA) in a practical trial using an innovative online trial  platform incorporating mobile activity monitors. The investigators expect to recruit and  retain 32 Veterans within 1 year. Inclusion Criteria:  -  Veterans in VA Rheumatology or Orthopedic clinics  -  Chronic knee osteoarthritis  -  Indication for joint injection  -  Previous joint injections for palliation  -  Patient expresses interest in increasing their physical activity  -  Patient is able to walk 1/2 mile per day Exclusion Criteria:  -  Intra-articular hardware or other contraindication to joint injection  -  Lack of smart phone  -  Acute exacerbation of osteoarthritis or knee pain  -  Unable or unwilling to identify a social sponsor  -  Comorbid condition that precludes safe exercise

Autism diagnostic referrals across the UK have doubled within the last five years. Covid-19  has further delayed diagnostic pathways, while innovation has not kept pace in assisting  clinical teams with low cost, fast, and unobtrusive pathways to shorten waiting times for  families of children with possible Autism. Sensor-based technology offers a potentially  cheap, small-scale, and unobtrusive way of collecting data while children interact seamlessly  with smart play objects and toys that allows a clear comparison with neuro-typical groups or  children.The present exploratory group intervention (intervention, interview, focus group,  and questionnaire) will map out and investigate clinical interaction through the use of  "Tangiball"-a new low-cost smart toy that is highly reliable and sensitive-that has the  potential to significantly reduce the timing of the diagnostic process in young children with  possible Autism. The "Tangiball" records user speed and accuracy of movement, which aligns  with variability between neuro-typical children and children with Autism, but is it an  acceptable clinical tool for diagnostics and play? Sensor-based technology offers a potentially cheap, small-scale, unobtrusive, and data rich  capture environment. Harnessing data capture whilst children interact seamlessly with play  objects and toys, will enable large-scale data insight into the active behaviour of children,  allowing clear comparisons with neurotypical groups. Data comparison can be modelled on  diagnostic manual descriptions, and would enhance pathology descriptions. Smart systems can  provide diagnostic evidence that can be compiled for children with disabilities and be  appropriately compared to neuro-typical baseline data. Borderline diagnosis and confusion can  be avoided, as collected data can then be used in addition to observable report. This data  elicits new information about the way children with Autism and associated developmental  disorders interact with their environment on a micro-level. Children with Autism when using  smart objects show slow movement, where deceleration during grasping reaching and placing  activities takes longer than neurotypical peers, the amplitude of reach speed is at its peak  higher than typical peers, maximum acceleration through space is slower, and the time taken  to reach speed peak is higher such that speed and accuracy can account for 76% of all  variance between children with Autism and typical peers. Children with Autism therefore  experience qualitative differences in the way they navigate their own body and interact with  objects within their own environment. Stereotyped or repetitive motor movements, hyper- or  hypo-reactivity to sensory input, and unusual interests in sensory aspects of objects, remain  central to Autism diagnosis. Atypical sensory and physical behaviour is estimated in 92% of  children with ASD and 67% of children with SEND equating to one million affected school  children. Diagnosis and clinical interaction of children with possible autism currently  relies on the use of subjective observational inventories (SOIs) such as ADOS, whilst  engaging children in unfamiliar surroundings, against the backdrop of dwindling resources.  Autism assessment referrals across KSS have doubled within the last five years. Covid-19 has  further delayed pathways. Innovation has not kept pace in assisting clinical teams with low  cost, fast and unobtrusive pathways to shorten waiting times. As clinical interactions with  younger children nearly always utilise toys to improve engagement, this Smart Toy solution  enables automated data capture-otherwise lost-by embedding sensors (e.g. RIFD, IMU Bluetooth)  in toys. Accurate data capture during object interaction has potential to significantly  reduce assessment time-a recognised problem highlighted in the NHS Long term plan.  "Tangiball" is a new low-cost smart toy that is highly reliable and sensitive that has the  potential to significantly reduce the timing of the diagnostic process in young children with  possible Autism. The "Tangiball" records user speed and accuracy of movement, which aligns  with variability between neuro-typical children and children with Autism. The present  exploratory group intervention study (intervention, interview, focus group, and  questionnaire) will map out and investigate clinical interaction through the use of sensors  that can tell the investigators how children are interacting with objects, and how this  diverges from neurotypical children. The project aims to establish the "Tangiball" as an  acceptable tool for clinical staff, children, and parents during clinical interaction; that  clinical interaction with a Smart Toy enables useful data to be gathered that can support the  diagnostic process in young children. With few smart devices embedded into everyday clinical  practice this project completes and trials an Internet of Medical Things Smart Toy for use in  child development clinics, to capture child interaction with objects and assist in profiling.  This can help determine appropriate pathways to care. Thirty children (n=15 with a formal  diagnosis of Autism Spectrum Disorder, n=15 neurotypical children with no prior referral to a  child development clinic), aged 2-5 years will be recruited over a period of 11 months via  clinical teams and through schools. The intervention will run either in clinic or in  children's homes. Children will play with the Smart Toy system during a 20 minute session.  Children will be matched according to age, and score on the four-strand "Hands-On" assessment  tool. Parents and children will complete a User Experience Questionnaire [UE-Q] which  assesses user acceptability and experience of the Smart Toy. Sessions will be recorded using  an SD card within the Smart Toy which records information on user speed and accuracy of  placement of the detachable segments of the toy when placed into the main hub of the toy. Ten  clinicians (comprising SALTs, Psychologists and Paediatricians) will be interviewed to  explore themes around smart toy use and acceptability. Data produced will explore the  acceptability and optimisation of triage using a novel, low-cost device that is highly  reliable and sensitive, including physical and behaviour profiling to increase timely  accurate identification of strengths and weaknesses in children in the early school-age, and  pre-school population (2 to 5 years) where there is a current pressure on identification. Inclusion Criteria:  1. Intervention phase:  child aged 2-5 years and either:  1. diagnosed with Autism  2. is a neurotypical child with no prior contact with a Child Development Clinical  Service for social communication problems  2. Focus groups, interviews, surveys:  either a parent of a child diagnosed with autism, or clinician who is involved in autism  diagnosis Exclusion Criteria:  1. Intervention phase:  1. neurotypical child has prior referral to Child Development Clinical Service Child  2. child is outside of age range  3. child not under the care of Child Development Clinical Service  2. Focus groups, interviews, surveys:  parent not of child with Autism, or a clinician not involved in autism diagnostic services

The Eva-PED-t project will evaluate implementation of a new therapy for eating disorders,  called PED-t (Physical Exercise and Dietary therapy), in a new treatment arena for such  illnesses. By this, Eva-PED-t evaluates effectiveness- and efficacy outcomes, with the latter  highlighting both the user-, the therapists- and the management perspectives. The research  group behind this initiative comprises the founders of the PED-t, and holds extensive  expertise on research methodology, eating disorders, health science, and exercise medicine,  affiliated high-ranked research-intensive universities. Previous documentation of poor  implementation of evidence-based knowledge in public health services reveal poor or no  translation of new research findings for improved screening, treatment or medical procedures  into real life settings. This may impair public health service outcomes, as less effective or  ineffective treatment or procedures are routinely preferred. In a randomized controlled  trial, the Eva-PED-t partnership recently found a new therapy for eating disorders (PED-t) to  be comparable effective to the currently recommended treatment (NCT02079935). Specific  advantages with PED-t, are the use of professionals not currently used in therapy of mental  disorders, and the efficiency of arranging therapy in groups, hence effectively dealing with  the high request for therapy. The Eva PED-t collaborative is motivated by the knowledge of  high prevalence of mental illnesses, for which there is a need to improve treatment access  and -efficiency. Adding to this scenario, is the new and more prevalent diagnosis of eating  disorders, binge eating disorder, for which specialized health services have no  prioritization for treatment. Addressing requirements for improved therapy access demands  investigation of new treatments and new ways of delivery. The PED-t responds to this request,  still recommendation for a broad implementation necessitate exploration of implementation  strategies and experiences. Implementation research intends to identify facilitating and obstructing elements in the  process of transferring evidence-based practices from controlled settings to naturalistic  settings. Unfortunately, the implementation of evidence-based knowledge is challenged by lack  of institutional resources and insufficient prioritization by the management, and lack of  prioritization by funders and academic researchers. As such, a lag time before evidence-based  knowledge from research is translated in to real world practice is typically estimated to be  about 14-20 years. The delay in implementation of evidence-based practice is found to be  specifically relevant in health care services, hence, ultimately depriving patients from best  practice. Exercise referral centers (ERC, also known as Healthy Living Centers) are part of  the municipally public health care, providing support for improved healthy living behavior.  Service users are confident by the professional skills in the ERC, and trust the service to  be evidence-based. However, there are a wide variety in program approaches and methodology,  most with no evidence-based foundation, and a lack of documentation on effects. Hence  originally, the UK National Institute for Health and Clinical Excellence (NICE) recommended  not to commission ERC in primary health care other than in well-designed research studies.  The ERC's are in an early progress, still exploring their role in public health care and  having stakeholders requesting evidence-based methods, and as such, identification of  successful interventions at the ERC's is necessitated.  The Eva-PED-t has the potential to pick up on the shortfalls in documentation of  effectiveness outcomes and exploration of efficacy of evidence-based interventions at the  ERC's, and the poor implementation of evidence-based treatment in public health services in  general. The EVA_PED intend to evaluate the implementation of the PED-t in the public health  care services ERC in terms of effectiveness and efficacy, and by a mixed methods design. By  relying on the original team behind the development of the PED-t to train the therapists,  inform and supervise the management, and to provide support during implementation, this  project has the potential to ease the implementation process. As such, the EVA-PED aim to  follow the request to evaluate the total implementation success (i.e. the sum of the  effectiveness of treatment and the experiences of implementation within the organization).  The researchers behind the EVA-PED finalized the evaluation of effectivity from PED-t on  treatment of eating disorders in 2018 (NCT02079935), bringing optimism on increased therapy  access, lowering barriers for treatment seeking behavior, and facilitating a more effective  treatment delivery. Having the PED-t research team initiating Eva-PED-t, this project will  bypass the delay in translation of evidence-based knowledge to real life settings. The  Eva-PED-t has the potential to identify any elements undermining optimal uptake of this  evidence-based treatment in public health services. Informed on previous challenges on  successful implementation of evidence-based procedures, Eva-PED-t grasp on these most  critical elements. Providing practical training and adequate time for preparations, mentoring  during therapy operation, relying on therapy elements similar to what the therapists have  practiced in their regular work, and by communicating, involving and motivating several  levels in the organizations (management and therapists); the EVA_PED target the most critical  elements previously found to impair successful implementation. Additionally, by involving  former patients and therapists from the PED-t intervention as user groups, combined with the  findings from in depth interviews in the corresponding groups of patients and therapists, the  EVA-PED will evaluate adjustments of the therapy and arrangement according to their  experiences and advices.  The EVA-PED-t project aims to evaluate the success of adopting and operating the  evidence-based PED-t in naturalistic settings like ERC's, physiotherapy clinics and  multidisciplinary medical centers. By this, the project intends to study effectiveness  outcomes and efficacy outcomes, with the latter highlighting both the user perspectives, the  therapists- and the management perspectives. A part of the efficacy outcomes, is evaluation  on the treatment fidelity by individual therapists.  This generate the following main- and secondary research questions (RQ):  Main RQ:  1. Which elements promotes or discourages the implementation of PED-t according to; a) the  therapists, and b) the management at the therapy cites?  Secondary RQ's:  1. How well is the implementation quality concerning treatment fidelity in a naturalistic  setting?  2. What are the experiences amongst the patients receiving PED-t in a naturalistic setting?  3. How effective is the PED-t in a naturalistic setting, evaluated in remission from  diagnosis, in rating of quality of life, in intensity of symptoms for depression,  anxiety and symptoms of an eating disorder, and in changes of eating- and exercise  behavior? Inclusion Criteria:  -  Diagnosis of bulimia nervosa or binge eating disorder  -  BMI 17.5 - 40  -  Women Exclusion Criteria:  -  Being/planning to become pregnant during the therapy period  -  Competitive athlete  -  Concurrent severe symptom- or personality disorder in need of other treatment options

This will be a phase I/II trial examining the safety and tolerability of pre-operative  mFOLFIRINOX in combination with peri-operative oral hydroxychloroquine (FHQ) in the treatment  of subjects with adenocarcinoma of the pancreas. Subjects will be staged prior to protocol  entry by contrast-enhanced helical abdominal CT scan done using a pancreas mass protocol or  EUS. Eligible subjects with biopsy-proven, resectable pancreatic adenocarcinoma without  evidence of venous or arterial involvement on CT scan receive HCQ orally in combination with  mFOLFIRINOX prior to surgery. Hydroxychloroquine will begin with the first dose of  mFOLFIRINOX and continue for 2 weeks post-operatively. Three to six weeks after the last dose  of mFOLFIRINOX, patients will undergo surgical exploration and pancreatectomy if technically  feasible and all toxicities have resolved. Pathologic specimens will undergo detailed  histopathologic and immunohistochemical evaluations with particular attention to the six  surgical margins of resection: the bile duct margin (for Whipple specimens), the margin of  pancreatic transection, the retroperitoneal margin, the proximal and distal duodenal margins  (for Whipple specimens), and the portal vein margin along the pancreatic head (for Whipple  specimens) or medial pancreas (for distal pancreatectomies). Tissue specimens will be stored  at -80C for future correlative studies of autophagy and tumor response to protocol therapy.  Ten to fourteen weeks following completion of successful surgical removal of their tumor,  subjects will undergo repeat staging studies per standard of care. Subjects will pursue  standard of care adjuvant therapy options at the discretion of their physician. A subject is deemed evaluable if they have received at least 3 of 4 cycles of chemotherapy  and at least 80% of the expected HCQ doses and undergo successful surgical extirpation their  disease. Patients will receive daily oral HCQ concurrently with neoadjuvant mFOLFIRINOX,  planned for 4 cycles. Each cycle of mFOLFIRINOX is 14 days, therefore 4 cycles will occur  over a period of 56 days. Oral HCQ will continue after completion of neoadjuvant chemotherapy  and extend 2 weeks post-operatively. Patients will undergo restaging scans after completion  of 4 cycles of mFOLFIRINOX. Within 3 to 6 weeks after completion of cycle 4 of mFOLFIRINOX,  patients will proceed for surgical resection. Patients will receive surveillance scans 10 to  14 weeks after completion of surgery.  Patients will receive HCQ every day starting at the first dose of mFOLFIRINOX. Capsules of  HCQ are available in 200 mg strengths. HCQ will be administered in divided doses (BID) for  doses to minimize nausea. Patients should be told to swallow the whole capsule in rapid  succession without chewing. The starting phase I dose for HCQ is 400 mg. Before accrual to  the next dose level may begin, all patients in a given cohort must complete the 2 months of  combination treatment (HCQ + mFOLFIRINOX), permitting toxicities to be assessed.  Dose will be assigned to patients using 3+3 Algorithm to identify the MTD. Dose level 1 is  400 mg hydroxychloroquine, dose level 2 is 800 mg hydroxychloroquine, and dose level 3 is  1200 mg hydroxychloroquine. If 0 first-dose DLTs are observed out of 3 patients treated with  the first dose-level, the next cohort of 3 patients may be enrolled and treated at the next  dose-level. If 1 out of the 3 patients treated with a dose-level experience a first-dose DLT,  up to 3 additional patients (6 total) will be enrolled at that dose-level. If only 1 out of  these 6 patients experiences a first-dose DLT, then the next cohort of 3 patients may be  enrolled and treated at the next dose-level. If ≥2 out of these 6 patients experience  first-dose DLTs, then dose escalation is stopped. Additional patients will be enrolled at the  prior lower dose-level to achieve a total of 6 patients. If ≥2 out of 3 patients in a cohort  experience a first-dose DLT, dose escalation will be stopped. Additional patients will be  enrolled at the prior lower dose-level, to achieve a total of 6 patients. If 0 or 1 out of 3  patients at the highest dose-level (1200 mg) experiences a DLT, additional patients will be  enrolled to achieve a total of 6 patients. If ≤1 out of these 6 patients experiences a DLT,  the 1200mg dose-level will be declared the maximal safe dose administered in this Phase 1  study. If ≥2 patients experience a DLT, additional patients will be enrolled at the prior  lower dose-level, for a total of 6 patients. If a DLT occurs in the first patient enrolled in  the trial, the first cohort of six patients will be assigned to Level 1. If a cohort of six  patients at Level 1 experiences more than one DLT, accrual to the trial will be paused, and  the trial will be referred to the GI DSMB for appropriate action. At the conclusion of the  dose escalation phase, the DSMB will meet to perform an interim review of safety data prior  to establishing the maximum tolerated dose for the phase 2 phase of the trial. The maximum  sample size of the study is 40 patients. Cohorts will be accrued until a new cohort would  exceed the maximum study size; therefore, the final sample size will be between 35 and 40  patients. Inclusion Criteria:  -  Subjects with biopsy-proven adenocarcinoma of the pancreas  -  Pancreatic protocol helical CT scan demonstrating absence of venous or arterial  involvement, consistent with NCCN guidelines for resectable disease  -  ECOG performance status ≤ 1  -  No active second malignancy except for basal cell carcinoma of the skin  -  Normal renal, hepatic, and hematologic function at the time of enrollment as evidenced  by:  -  Serum creatinine level ≤1.5 the upper limits of normal  -  Serum total bilirubin level ≤1.5 X ULN  -  White blood cell count ≥ 3.5x109/ml per ml and platelet count ≥ 100x109 per ml  -  For subjects with obstructive jaundice, the biliary tract must be drained with a  temporary plastic or a short permanent metallic biliary stent  -  Ability to understand and the willingness to sign a written informed consent document. Exclusion Criteria:  -  Subjects deemed surgically unresectable or subjects unwilling to undergo surgical  resection.  -  Subjects who have received chemotherapy within 12 months prior to study entry.  -  Subjects who are found to have loss-of-function mutations in DPYD or UGTA1 by Oneome  pharmacogenomic testing, resulting in increased risk of mFOLFIRINOX toxicity. DPYD  mutations have been noted in 5% of the overall population. Homozygous UGT1A1 mutations  have been noted in 10% of North Americans.  -  Prior use of radiotherapy or investigational agents for pancreatic cancer.  -  Any evidence of metastasis to distant organs (liver, lung, peritoneum).  -  Cross sectional imaging suggesting portal vein, superior mesenteric artery, hepatic  artery involvement that would make the patient borderline resectable or locally  advanced  -  Symptomatic or endoscopic evidence of gastric outlet obstruction.  -  Concurrent malignancies with evidence of active or measurable disease except basal  cell carcinoma of the skin.  -  Inability to adhere to study and/or follow-up procedures.  -  History of allergic reactions or hypersensitivity to the study drugs (chloroquine,  hydroxychloroquine, 5-Fluorouracil, Leucovorin, Oxaliplatin, Irinotecan).  -  Other concurrent experimental therapy.  -  The effects of HCQ, and mFOLFIRINOX on the developing human fetus are unknown. For  this reason women of child-bearing potential and men must agree to use adequate  contraception (hormonal or barrier method of birth control; abstinence) prior to study  entry and for the duration of study participation. All females of childbearing  potential must have a blood test or urine study within two weeks prior to registration  to rule out pregnancy. Should a woman become pregnant while participating in this  study, she should inform her treating physician immediately. If a man impregnates a  woman while participating in this study, he should inform his treating physician  immediately as well.  -  Because patients with immune deficiency are at increased risk of lethal infections  when treated with bone marrow-suppressive therapy, HIV-positive patients are excluded  from the study. For patients receiving combination anti-retroviral therapy, the  potential impact of pharmacokinetic interactions with HCQ and mFOLFIRINOX is unknown.  Appropriate studies may be undertaken in patients with HIV and those receiving  combination anti-retroviral therapy in the future.  -  Due to the risk of disease exacerbation, patients with porphyria are ineligible.  -  Patients with psoriasis are ineligible unless the disease is well controlled and they  are under the care of a specialist who agrees to monitor the patient for  exacerbations.  -  Patients requiring the use of enzyme-inducing anti-epileptic medication that includes:  phenytoin, carbamazepine, phenobarbital, primidone or oxcarbazepine are excluded.  -  Patients with previously documented macular degeneration or diabetic retinopathy are  excluded.  -  Baseline EKG with QTc >470 msec (including subjects on medication). Subjects with  ventricular pacemaker for whom QT interval is not measurable will be eligible on a  case-by-case basis.

30 adults, aged 40 and older with mild to moderate COPD, will be recruited for this study.  Participants must be willing to continually wear a FitBit activity monitor, have access to a  smartphone or Wi-Fi/Data-enabled iPad, and be willing to complete respiratory muscle strength  training exercises as well as reports on their smartphone at least 5 times per week for a  6-week period. Participants will be given a bluetooth inhaler device and a training app  (RESP-FIT). This application will collect inhaler data and allows patients to self-report  their daily symptoms. The goal of this study is to test whether use of the personalized  inhaler device with the app strengthens lung function, promotes physical activity, and  improves disease symptom self-management in persons with COPD. RESP-FIT. The RESP-FIT program is a 6-week respiratory muscle strength training intervention  adapted from previous respiratory muscle strength training (RMST) training regimens,  consisting of 1) five training days/week using combined inspiratory and expiratory muscle  training, consisting of breathing in and out against a combine inspiratory and expiratory  muscle strength trainer (IMST/EMST), 2) individualized, progress-based text message training  reminders and prompts related to timing and intensification calibration, and 3) use of a  Fitbit for remote monitoring of physical activity and hours slept at night. Similar to other  muscle strength training programs, exercises are done at regular intervals during the week (5  breaths, 5 times a day, 5 days a week; the participant will receive graphical illustration of  RESP-FIT training frequency and intensity achieved, and based on their training regimen, will  be prompted and/or reinforced via SMS text messaging). As the use of an accelerometer or  remote tracking device alone may affect physical activity, a control group will receive only  the Fitbit. This study proposes to assess the feasibility and initial efficacy of RMST by  obtaining estimates of variability in fatigue secondary to dyspnea, using a  technologically-enhanced RESP-FIT intervention. Our overarching hypothesis is that a training  regimen consisting of RMST along with technology-enhanced symptom-tracking will decrease  dyspnea, dyspnea-related activity avoidance, and fatigue. Additionally, this application  proposes to further develop Smartphone Airway Monitoring System (SAMS) which currently  integrates EMA probe questions covering COPD symptoms and preventive care use with the new  functions, use in an adult population with COPD, video captured training technique and  logging of RMST training sessions. Up to thirty adults with COPD (age over 40) will complete  the study and use the SAMS app for 6 weeks in the natural environment. We will evaluate the  acceptability, feasibility, adherence, and performance of RESP-FIT + SAMS through  quantitative methods to further optimize the app and related study procedures for the next  phase of testing (i.e., large scale efficacy RCT). Inclusion Criteria:  -  40 years of age or older; and  -  Able to read and write English; and  -  Diagnosed with mild to moderate COPD (PFT values: FEV1/FVC <0.7 and FEV1% predicted <  50% - within the past 6 months); and  -  Dyspnea score of greater than "2" on the Modified Medical Research Council (MMRC)  questionnaire. Exclusion Criteria:  -  • Pregnant female or less than 1 year post-partum; or  -  Diagnosed cognitive deficit or observed lack of understanding during the informed  consent process; or  -  Mobility impairment; or  -  Lack of 3g WiFi access in place of residence; or  -  Unwillingness to wear physical activity tracker daily, follow protocol, and/ or  attend study visits.

Intrauterine adhesions (IUA) are the major long-term complication of intrauterine procedures  and are associated with pelvic pain, menstrual disorders, obstetrical complication and  infertility.  Womed Leaf is a medical device specifically designed for intrauterine use that prevents  intra-uterine adhesions. It is a film that acts as a mechanical barrier to keep uterus walls  separated during healing. It is then naturally discharged through the cervix and vagina in  less than 30 days.  The PREG1 clinical investigation is designed to evaluate Womed Leaf safety under clinical  conditions, in women scheduled for a hysteroscopic myomectomy as well as its efficacy. Intrauterine adhesions (IUA) are defined as "fibrous strings at opposing walls of the uterus  and/or cervix leading to partial or complete obliteration of the cavity". IUAs are the major  long-term complication of intrauterine procedures and are associated with pelvic pain,  menstrual disorders, obstetrical complications and infertility.  Womed Leaf™ is a sterile, degradable polymer film specifically design for intrauterine use.  It is inserter in the uterus like an intrauterine device. Once released it will self-deploy  into the uterine cavity to form a mechanical barrier keeping uterus walls separated during  healing, for several days, thus preventing the formation or recurrence of intrauterine  adhesions. It is degraded and discharged naturally through the cervix and vagina in less than  30 days.  The PREG1 clinical investigation is a prospective multicenter, single arm study, designed to  evaluate Womed Leaf safety under clinical conditions, in women scheduled for a hysteroscopic  myomectomy as well as its efficacy in preventing IUA at second look hysteroscopy. Inclusion Criteria:  -  Women ≥ 40 years AND no childbearing wish, OR history of permanent sterilization;  -  Subject scheduled for hysteroscopic myomectomy for one or more myoma(s) where one  myoma is at least 10 mm in size (≥10mm) as estimated by pre-operative ultrasound  measurement of the largest diameter,  -  Hysterometry prior to device insertion ≥ 6cm and ≤ 9cm.  -  Subjects who are willing to provide a written informed consent as approved by the  applicable Ethics Committee prior to participating in this clinical investigation.  -  Subjects who can comply with the study follow-up or other study requirements Exclusion Criteria:  Pre-operative exclusion criteria:  -  Current pregnancy  -  Abnormal uterine cavity according to ESHRE classification I to VI, such as unicornis,  bicornis, septate, duplex  -  Known or suspected endometrial hyperplasia  -  Medical history of cervical or endometrial cancer  -  Active pelvic infection or medical history of pelvic peritonitis  -  Intrauterine device in situ  -  Known contraindication or hypersensitivity to PEO or PLA, and to medications such as  aspirin….  -  Concurrent medical condition with a life expectancy of less than 12 months  -  Full endometrial ablation  Per-operative exclusion criteria:  -  Adenomyosis  -  Inflammation (endometritis)  -  Abnormal uterine cavity  -  Hysterometry < 6cm or >9cm  -  Any complication during the intervention that is deemed to potentially interfere with  the objective of the study by the investigator

This phase II trial studies how effective talazoparib and temozolomide are for treating  participants with extensive-stage small cell lung cancer that has come back after an initial  chemotherapy treatment. Talazoparib, a PARP inhibitor, may stop the growth of tumor cells by  preventing them from repairing their DNA. Chemotherapy, such as temozolomide, work in  different ways to stop the growth of tumor cells, either by killing the cells, by stopping  them from dividing, or by stopping them from spreading. Giving talazoparib and temozolomide  may work better in treating participants with extensive-stage small cell lung cancer than  either one alone. PRIMARY OBJECTIVES:  I. Evaluate the efficacy of talazoparib in combination with temozolomide as measured by  objective response rate (ORR).  SECONDARY OBJECTIVES:  I. To evaluate the efficacy of talazoparib plus temozolomide as measured by progression-free  survival (PFS), overall survival, duration of response, and time to response.  II. To evaluate the safety, tolerability of talazoparib plus temozolomide. III. To evaluate  the pharmacokinetics of talazoparib when given in combination with temozolomide.  IV. To evaluate patient reported outcomes per the Patient Reported Outcomes version of the  Common Terminology Criteria for Adverse Events (PRO-CTCAE).  EXPLORATORY OBJECTIVES:  I. To identify potential biomarkers associated with response to study drug treatment.  OUTLINE:  Participants receive temozolomide orally (PO) on days 1-5 and talazoparib PO once daily (QD)  on days 1-28. Courses repeat every 28 days in the absence of disease progression or  unacceptable toxicity.  After completion of study treatment, participants are followed up at 30 days and then up to 1  year. Inclusion Criteria:  -  Able to provide informed consent.  -  Cytologically or histologically confirmed small cell lung cancer (SCLC) with  extensive-stage disease.  -  Relapsed (progressed within 6 months) or refractory (progressed during or within 4  weeks of completing 1st line platinum based regimen).  -  Measurable disease, as per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1.  -  Archival or fresh tissue biopsy available for exploratory analyses.  -  Eastern Cooperative Oncology Group (ECOG) performance status of =< 1.  -  Able to swallow the study drugs, has no known intolerance to study drugs or  excipients, and able to comply with study requirements.  -  Female participants of childbearing potential must have a negative pregnancy test at  screening and must agree to use a highly effective birth control method (defined in  protocol) from the time of the first study drug treatment through 45 days after the  last study drug treatment.  -  Male participants must use a condom when having sex from the time of the first study  drug treatment through 105 days after the last study drug treatment. Contraception  should be considered for a non-pregnant female partner of childbearing potential.  -  Male and female participants must agree not to donate sperm or eggs, respectively,  from the first study drug treatment through 105 days and 45 days after the last study  drug treatment, respectively.  -  Female participants may not be breastfeeding at baseline through 45 days after the  last study drug treatment.  -  Absolute neutrophil count (ANC) >= 1,500/mcL  -  Platelets >= 100,000/mcL  -  Hemoglobin >= 9 g/dL or >= 5.6 mmol/L without transfusion or erythropoietin (EPO)  dependency (within 7 days of assessment)  -  Glomerular filtration rate (by Cockroft-Gault or equivalent estimation) >= 30 mL/min  -  Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase [SGOT]) and  alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 X  ULN OR =< 5 X ULN for participants with liver metastases  -  Serum total bilirubin =< 1.5 X upper limit or normal (ULN) OR direct bilirubin =< ULN  for participants with total bilirubin levels > 1.5 ULN  -  International normalized ratio (INR) or prothrombin time (PT) =< 1.5 X ULN unless  participant is receiving anticoagulant therapy, as long as PT or partial  thromboplastin time (PTT) is within therapeutic range of intended use of  anticoagulants  -  Activated partial thromboplastin time (aPTT) =< 1.5 X ULN unless participant is  receiving anticoagulant therapy, as long as PT or PTT is within therapeutic range of  intended use of anticoagulants Exclusion Criteria:  -  Has not recovered (recovery is defined as Common Terminology Criteria for Adverse  Events (CTCAE) version (v)4 grade =< 1 or return to baseline) from the acute  toxicities of previous therapy, except treatment-related alopecia or laboratory  abnormalities otherwise meeting eligibility requirements.  -  Best response of progressive disease per RECIST 1.1 to first-line platinum doublet  chemotherapy.  -  Has received more than 1 line of cytotoxic therapy  -  Prior immunotherapy and targeted therapies (including rovalpituzumab tesirine)  are allowed.  -  Prior treatment with a PARP inhibitor (not including iniparib) or temozolomide.  -  Use of antineoplastic therapies within 14 days before study treatment initiation.  -  Use of any other investigational agent within 14 days before study treatment  initiation.  -  Received radiation therapy within 14 day before study treatment initiation (single  fraction palliative radiotherapy is allowed without a washout).  -  Prior thoracic irradiation and prophylactic cranial irradiation are allowed.  -  Major surgery within 14 days before study treatment initiation.  -  Diagnosis of myelodysplastic syndrome (MDS).  -  Gastrointestinal disorder affecting absorption.  -  Current or anticipated use of a prohibited P-gp inhibitor or P-gp inducer or BCRP  inhibitors.  -  History of another cancer within 2 years before study treatment initiation, with the  exception of fully treated cancers unlikely to affect the assessment of the study  treatment safety or efficacy including early stage breast, prostate, nonmelanomatous  skin, thyroid, cervix and endometrial cancer.  -  Any condition (concurrent disease, infection, or comorbidity) that interferes with  ability to participate in the study, causes undue risk, or complicates the  interpretation of safety data, in the opinion of the investigator.

Determine whether a facilitated local change team intervention improves a probation  organization's client-level medication for opioid use disorder (MOUD) outcomes and  implementation outcomes relative to baseline across multiple sites. Determine whether  client-level outcomes are further enhanced by the introduction of Peer Support Services. Background: The purpose is to determine whether a facilitated local change team (LCT)  intervention improves linkage to medication for opioid use disorder (MOUD) and implementation  outcomes, and whether participant-level outcomes are further enhanced by the use of Peer  Support Specialists (PSS).  Methods/Design: This Type 1 hybrid implementation-effectiveness study involves a pre-post  design (implementation study) followed by a randomized trail of PSS (effectiveness study).  The study is conducted at 7 performance sites in 3 states.  Phase 1 (Core Implementation Study): The Exploration, Preparation, Implementation,  Sustainability (EPIS) framework is used to guide system-change through facilitated LCTs  consisting of probation and community treatment staff who are given a core set of  implementation strategies which are used to conduct a needs assessment and set goals. The  overall objective is to improve linkage to the continuum of evidence-based care for  justice-involved individuals with opioid use disorder (OUD). Organizational (program-level)  and staff survey are collected at the end of each EPIS stage (baseline Exploration, end of  Preparation, end of Implementation, and 12 months [Sustainability]). Implementation outcomes:  Organizational engagement in MOUD (primary), plus changes in staff knowledge/attitudes and  organizational outcomes (secondary).  Phase 2 (Effectiveness Study of PSS): After completing implementation, 680 adults on  probation are randomized to receive PSS vs. treatment as usual (TAU), with assessments at  baseline, 3, 6, and 12 months. This trial tests whether having a trained peer improves  clinical outcomes beyond effects of Core Implementation. Implementation program-level  outcomes include organizational engagement in MOUD use (primary outcome); changes in staff  knowledge and attitudes about MOUD, commitment and efficacy, readiness for change;  organizational attitudes for change, commitment and efficacy (secondary outcomes).  Client-level effectiveness outcomes include participant engagement in MOUD (primary outcome),  probation revocation, illicit opioid use, and overdoses (secondary outcomes). Other aims  include identifying barriers and facilitators, and cost-benefit analysis of PSS.  Primary Research Questions:  The primary aim is to test the effectiveness of PSS compared to TAU (agency approach after  implementation) on outcomes of individuals on probation: Engagement in MOUD (primary  effectiveness outcome), probation revocation (secondary), illicit opioid use (secondary), and  overdose (tertiary).  The second aim is to test the effectiveness of EPIS-based Core Implementation Intervention  relative to baseline on engagement in MOUD (primary implementation outcome).  The third aim is to test the effects of the EPIS implementation strategies relative to  baseline on program-level (organizational and staff-level) outcomes.  The fourth aim is to conduct a cost-benefit analysis of implementing PSS compared to TAU.  The fifth aim is to identify organizational and staff barriers and facilitators to  intervention implementation by conducting qualitative interviews with key probation and  community treatment stakeholders who are managing and delivering the MOUD program. Inclusion Criteria:  -  Community Provider Staff: Any front-line treatment provider at an agency participating  in this study who: (a) provides support to MOUD clients, (b) has an active caseload  including some individuals on probation, (c) has been employed by the community  treatment agency at least 3 months, and (d) willing to commit to 12 months to the  project.  -  Probation/Parole Staff: Any probation officer (PO) at an agency participating in this  study who (a) has an active caseload, (b) has been employed at the probation agency at  least 6 months, and (c) is willing to commit to 12 months to the project.  -  Individuals on Probation: (a) 18 years or older, (b) committed to probation within 90  days prior to study enrollment, (c) English speaking, (d) diagnosed with OUD, (e) have  stable method of contact in community Exclusion Criteria:  -  Individuals on Probation: Currently incarcerated or in a court-mandated inpatient  treatment.

This study was aimed to evaluate the post-infection cognitive functions of adult individuals  with COVID-19. 50 individuals with COVID-19 and 50 healthy control groups were included in  the study. Cognitive functions of individuals with COVID19 compared with healthy individuals. This study was aimed to evaluate the post-infection cognitive functions of adult individuals  with COVID-19. Fifty COVID-19 patients, aged between 18-50 years, who had positive RT-PCR  test in the last 60 days and later recovered, were included in the study. The study group was  compared with the control group consisting of 50 healthy individuals in whom gender, age and  education year has not difference significantly. Participants' global cognitive skills were  measured by the Montreal Cognitive Assessment Test (MoCA), the Clock Drawing Test and memory  functions, the Öktem Verbal Memory Processes Test (Ö-SBST), the attention functions by the  Digit Span Forward and Digit Span Backwards Test, the executive functions by Categorical  Fluency, Phonemic Fluency, the Stroop Test, Trail Making Test A and B, visuospatial skills  were evaluated with the Rey-Osterrieth Complex Figure Test (ROCF), and behavioral symptoms  were evaluated with the Neuropsychiatric Inventory (NPI). The study group was evaluated  between 21 and 60 days from the onset of the disease. Inclusion Criteria:  -  Having positive for the COVID-19 RT-PCR test and turned negative in the last 60 days.  -  be 18-50 years old  -  21 days have passed since the onset of the disease Exclusion Criteria:  -  Having any neurological or psychiatric illness

This is a single-centre prospective, non-randomized trial to investigate the efficacy of  cryotherapy in patients with localized prostate cancer.The aim of study is to investigate the  safety profile of cryotherapy in the treatment of prostate cancer and to evaluate the  oncological control of prostate cancer by means of cryotherapy focal treatment. Conventional treatment options for localized prostate cancer include prostatectomy,  radiotherapy and active surveillance. However, prostatectomy and radiotherapy carry certain  degree of morbidity, including the risks of urinary incontinence, erectile dysfunction and  injury to the structures in the proximity. Active surveillance carries the risk of disease  progression and psychological distress to the patients. Focal therapy employs the concept of  only destroying the significant lesion, resulting in disease cure and improved functional  outcome. Among the different options of focal therapy, cryotherapy is one of the most  commonly employed energy sources. It exerts its effect through freezing of tissue and  vascular injury, leading to destruction of cancer tissue. Our study aims at assess the safety  and effectiveness of such treatment in prostate cancer management Inclusion Criteria:  -  Men aged between 40 - 85 years  -  Visible index lesion(s) on MRI  -  Found to have localized prostate cancer after MRI-USG fusion targeted biopsy:  1. Clinical tumour stage <= T2, or  2. Gleason score <= 7, or  3. PSA <= 20 ng/ml Exclusion Criteria:  -  Patients unfit for contrast MRI exam  -  Patients with active urinary tract infection  -  Patients with bladder pathology including bladder stone and bladder cancer  -  Patients with urethral stricture  -  Patients with neurogenic bladder and/or sphincter abnormalities  -  Patients who fail to give informed consent

The unifying objective of this project is to determine whether peanut oral immunotherapy (PN  OIT) induced clinical tolerance in the context of food allergy is significantly associated  with the expansion of a specific regulatory T cell subset (CD45RA- CD25++ FoxP3++) that is  thought to be inducible in the gut-associated lymphoid compartment and associated with  immunological tolerance.  The hypothesis of the study is that the induction of Treg cells will be associated with  clinical tolerance.  The investigators will measure the change from baseline of induced Treg cells as a frequency  of total CD4 T cells during active treatment and compare that between participants who  achieve significant clinical tolerance (Tolerance and Partial Tolerance Groups as defined  below) and those who do not (Treatment Failure Group). Clinical Objectives:  1. To evaluate whether PN OIT induces increased tolerance, defined as a statistically  significant increase in the median eliciting dose (ED) from a double-blind  placebo-controlled food challenge (DBPCFC) before and after treatment with PN OIT and  after subsequent allergen avoidance.  2. To evaluate whether PN OIT induces clinical desensitization, defined as 1) a median  10-fold or greater increase in ED at DBPCFC before and after PN OIT treatment period 2)  a statistically significant higher median ED at DBPCFC following treatment period  between active and control treatment; and 3) a significantly lower frequency of  accidental ingestion reactions in active versus control treatment.  3. To evaluate the safety of PN OIT.  Mechanistic Objectives:  1. To determine whether PN OIT induces a statistically significant increase in the TCR  clonal diversity of Treg populations during active treatment among participants who  achieve increased clinical tolerance (Tolerance and Partial Tolerance Groups as defined  in clinical endpoints) versus the Treatment Failure Group.  2. To determine whether PN OIT suppresses mast cells by inducing a significant suppression  of the median ED on end-point dilution skin testing in actively treated participants by  the end of maintenance therapy.  3. To determine whether PN OIT suppresses basophils as defined by a 10-fold suppression of  peanut-specific basophil ED in actively treated participants by end of a maintenance  period.  4. To determine whether either mast cell or basophil suppression at the end of maintenance  therapy is significantly associated with clinical outcomes following avoidance.  Exploratory Objectives:  1. To describe the gene expression profiles and clonal diversity of regulatory and effector  T cell subsets before and after OIT to better understand the phenotype and ontogeny of  these subsets and potentially discover new therapeutic pathways.  2. To engineer human MHC class II tetramers on common HLA backgrounds and map T cell  epitopes of the dominant peanut allergens for use in validating earlier findings and for  future studies of peanut-specific immune responses in humans. Inclusion Criteria:  -  Diagnosis of peanut allergy by a positive skin prick test to peanut (reaction wheal at  least 5 mm larger than saline control) and by medical history or Serum peanut-specific  IgE >5 kU/L at screening visit.  -  Ara h 2 specific IgE >0.35 kU/L at screening visit  -  Ability to provide informed consent.  -  Males and females of all ethnic/racial groups aged 7-55 years old who are otherwise  healthy.  -  React to less than 443 mg of peanut protein during DBPCFC1 Exclusion Criteria:  -  History of severe anaphylaxis as defined by hypoxia (cyanosis or SpO2 <92% during  reaction), documented hypotension (documented systolic BP >30% below predicted normal  for sex, height, weight or from known baseline), neurological compromise (confusion,  loss of consciousness), or incontinence.  -  Severe or Moderate asthma as defined using the severity criteria of the current NHBLI  Guidelines for the Diagnosis and Management of Asthma  (http://www.nhlbi.nih.gov/guidelines/asthma/).  -  Poorly-controlled asthma as defined by FEV1 <80% or any of the following symptoms:  nighttime awakening >2 days/week or rescue medication use >2 days / week.  -  Diagnosis of other severe or complicating medical problems, including autoimmune or  chronic immune inflammatory conditions or gastrointestinal inflammatory conditions,  including Celiac Disease, Inflammatory Bowel Disease and Eosinophilic Gastrointestinal  Disorders  -  Inability to cooperate with and/or perform oral food challenge procedures.  -  Primary Immune Deficiency  -  Allergy to oat confirmed by skin prick testing and history  -  Current use of beta blockers, angiotensin converting enzyme inhibitors, or monoamine  oxidase inhibitors  -  Women of childbearing potential who are pregnant, planning to become pregnant, or  breastfeeding  -  Hemoglobin level less than 12.5 gm/dL at screening. Weight <23 kg  -  Use within the past 6 months of other systemic immunomodulatory treatments including  allergen immunotherapy, or use of biologics with an immune target, including  omalizumab.  -  Past or current medical problems or findings from physical examination or laboratory  testing that are not listed above, which, in the opinion of the investigator, may pose  additional risks from participation in the study, may interfere with the participant's  ability to comply with study requirements or that may impact the quality or  interpretation of the data obtained from the study may also exclude a participant from  the study.

The aim of the research is to evaluate the clinical value of fractional exhaled nitric  oxide(FeNO) ,impulse oscillometry(IOS) and mid-expiratory flow (MEF) in patients with cough  variant asthma. The present study has the following objectives:  to evaluate the relationship between BHR and mid-expiratory flow, to assess the diagnostic  accuracy of fractional exhaled nitric oxide，impulse oscillometry and mid-expiratory flow in  CVA with special regard to its discriminating value between CVA and other causes of a chronic  cough, to estimate prognostic value of BHR and fractional exhaled nitric oxide (FeNO) count  in predicting response to asthma treatment. Inclusion Criteria:  age 18-65 years old. Cough as the sole or predominant symptom lasting for at least 8 weeks,  with no radiographic evidence of lung diseases. Exclusion Criteria:  treatment of any oral corticosteroid in the last 4 weeks, and respiratory tract infection  within 8 weeks.  smoking (min. 6 months) had asthma or other lung diseases, including obliterative  bronchiolitis, bronchiectasis,and cystic fibrosis.

Primary Objective:  To evaluate the safety of Gla-300 in insulin naïve T2D participants uncontrolled on oral  antihyperglycemic drugs  Secondary Objective:  To assess the efficacy of Gla-300 on glycemic control in insulin naïve T2D participants  uncontrolled on oral anti-hyperglycemic drugs To assess change in participant's treatment  satisfaction using DTSQs (Diabetes Treatment Satisfaction Questionnaire) The maximum study duration per participant is 27 weeks including a screening period of up to  2 weeks, a 24-week treatment period and a post-treatment follow-up phone call visit after 3  days after the end of treatment. Inclusion Criteria:  -  Participants with Type 2 diabetes mellitus  -  Participants who are insulin naïve on at least one oral antihyperglycemic drug  (metformin,sulfonylurea, thiazolidinedione, DPP-4 inhibitor, SGLT-2 inhibitor,  glinide, α-glucosidase inhibitor) with or without glucagon-like peptide 1 receptor  agonists (GLP-1 RAs) for a minimum period of 6 months prior to screening.  -  HbA1c between 7.5% (58 mmol/mol) and 10% (86 mmol/mol) inclusive, during screening. Exclusion Criteria:  -  History of severe hypoglycemia requiring emergency room admission or hospitalization  within 3 months prior to screening visit.  -  Proliferative retinopathy or maculopathy requiring treatment according to the  Investigator  -  Treatment with any insulin including basal insulin, mixed insulin (premixes), rapid  insulin, and fast-acting insulin analogues in the last 6 months before screening visit  (use ≤10 days in relation to hospitalization or an acute illness is accepted).  -  Use of systemic glucocorticoids (excluding topical application or inhaled forms) for 2  weeks or more within 8 weeks prior to screening visit.  The above information is not intended to contain all considerations relevant to a patient's  potential participation in a clinical trial.

The study investigates the effects of pain and exercise training via telerehabilitation  method on pain, pain beliefs, trunk mobility, functionality, and quality of life in  individuals with low back pain caused by facet joint arthrosis. Forty - five individuals are  planning to include in the study. Participants will be randomly assigned to one of the three  groups: Group 1: Pain education + exercise training group, Group 2: Exercise training group,  and Group 3: Control group. The same physiotherapist will make evaluations via an online  conference system. Group 1 will have pain neuroscience education and progressive therapeutic  exercise training in a session for six weeks, twice a week, and Group 2 will have progressive  therapeutic exercise training in a session for six weeks, twice a week, for six weeks, in  total twelve sessions. Group 3 participants will be taken to the waiting list. Clinical and  demographic data of the 45 participants in the study will be taken pre and post  interventions. The primary outcomes are; the Numeric Pain Rating Scale (NPRS) and the  Oswestry Disability Index (ODI). Secondary outcomes are the Active Straight Leg Raise Test  (A- SLR), The Pain Belief Questionnaire (PBQ), and the Short Form Quality of Life Form  (SF-12). Statistical analysis will be run through the SPSS 20.0 package program. 'Pain Neuroscience Education (PNE) is one of the cognitive approaches among conservative  treatments, and has been one of the most inquisitive approaches. The content of the education  includes the physiology of pain, types of pain, the areas in which it is represented in the  brain, its effect on body image, and psychosocial dimensions. Education aims to break the  patient's misinformation and perception about pain and teach how to manage pain. It aims to  inform patients about the neurophysiological and neurobiological processes related to the  pain experience and help change their misinformation about pain conditions. Improved pain  knowledge changes attitudes and beliefs about pain, reduces destructive thoughts, and fear of  pain, and improves physical performance. It is known to reduce pain and disability according  to short-term results in patients with chronic pain with central sensitization. According to  systematic reviews, PNE is moderately effective in patients with chronic musculoskeletal  pain. In addition, it is stated that the use of educational approaches based on the  neurophysiology of pain offers clinical benefits not only in physical terms but also in  psychosocial terms. Since maladaptive psychosocial factors (for example, negative emotions,  poor self-efficacy, and maladaptive beliefs) are associated with pain behaviors, it is  thought that increasing pain knowledge will have an impact on pain perception. In a study  conducted on patients with musculoskeletal pain who experience different types of pain, an  inverse relationship between pain intensity and knowledge level was shown.  Due to the COVID-19 pandemic, the interest in the telerehabilitation method has increased,  and it has become reachable easier with more evidence value on this subject. However,  physiotherapists are healthcare professionals who work face-to-face with patients; depending  on the pandemic curfews, the World Health Organization (WHO) has recommended not to continue  face-to-face practices, except in emergencies, to protect patients' and physiotherapists'  health. While digital options such as sensors, wearable technologies, virtual reality, and  artificial intelligence are considered a solution, Tele-Rehabilitation (TR) can be the most  practical, reachable, and cheaper solution to existing problems.  Systematic research and meta-analyses examining the effect of the telerehabilitation method  and comparing it with traditional rehabilitation have revealed similar gains in outcome  measures such as pain intensity and quality of life. It has been reported that simultaneous  TR has comparable and effective results with face-to-face rehabilitation on pain and function  in musculoskeletal problems. The telerehabilitation method is effective and cost-effective,  especially in low back pain. Revealing the effects with more specific patient groups is the  common recommendation of the studies.  In line with this information, the study's primary purpose is to determine the effects of PNE  and progressive therapeutic exercise training given by the physiotherapist with the  telerehabilitation method on pain, disability, pain beliefs, and quality of life. The  secondary aim is to compare the effectiveness of progressive therapeutic exercise training  alone or with PNE. Inclusion Criteria:  -  volunteering,  -  being the ages of 40 to 64  -  having a diagnosis of Grade 1 or 2 facet joint arthrosis according to Pathria  classification  -  having pain for at least 12 weeks, primarily due to facet joint arthrosis  -  having a pain score between 3 and 8 according to the Numerical Pain Scale (NRS)  -  not having received education about pain before,  -  having computer and internet access Exclusion Criteria:  -  having a BMI of 30 and above  -  to have had conservative treatment or surgery in the lumbar region in the last 6  months,  -  having severe deformity in the lower extremity  -  having red or orange (pregnancy, disc pathology, infection, fracture, cancer,  stenosis, severe osteoporosis, schmorl nodule, cauda equina syndrome, etc.) signs  defined for low back pain  -  having a regular exercise habit,  -  having a seronegative rheumatological disease,  -  having general pain syndrome.

The proposed research is a feasibility pilot trial designed to optimize the remote collection  dried blood spots (DBS) from a finger stick and the analysis of fatty acid from the DBS and  to optimize the analysis of mitochondria activity (or energy metabolism) from peripheral  blood mononuclear cells (PBMC) or white blood cell samples. Participants in this study will  provide a blood sample from venous blood draw and finger sticks. One finger stick collection  will be completed remotely using a DBS kit that is sent through the mail while the other  finger stick collection will be completed at the research site. These samples will be use to  optimize the method for measuring fatty acids and mitochondria function as well as measure  other lipids, insulin, glucose and markers of inflammation using established protocols.  Demographic, dietary, sleep, and physical activity information will be measured using  questionnaires, while height and weight will be measured to calculate body mass index (BMI). The primary objectives of the study are  -  To optimize remote blood collection and laboratory analysis of polyunsaturated fatty  acids (PUFAs) in dried blood spot (DBS) samples  -  To optimize the analysis of mitochondria function in fresh and frozen peripheral blood  mononuclear cells (PBMC) Inclusion Criteria:  -  18 years of age or older  -  Nonsmoking Exclusion Criteria:  -  Diabetes

Chronic pain and unhealthy drinking are common co-occurring conditions among patients  presenting to primary care. Given their impact on functioning and medical outcomes, there  would be considerable benefit to developing an accessible, easily utilized, integrative  approach to reduce unhealthy alcohol use and pain that can be readily incorporated into the  primary care setting. The objective of this study is to test a smartphone-based intervention  for reducing unhealthy alcohol use and pain in primary care patients, determine the  feasibility of implementing this intervention in the primary care setting, provide effect  size estimates of the intervention on drinking and chronic pain outcomes. Heavy alcohol use represents a significant risk for morbidity and mortality. Unfortunately,  addressing unhealthy patterns of alcohol use in primary care is often a challenge as patients  typically present with co-morbid conditions that: (1) may make unhealthy drinking a lower  priority health issue and (2) may impact the capacity for sustained alcohol-related change.  Chronic pain is among the most common of these conditions among primary care patients. Pain  is a frequent source of distress and disability among primary care patients and is one of the  most frequent causes for visits. Pain is also an important trigger for alcohol use among  primary care patients who drink and is associated with the experience of negative  alcohol-related consequences and unhealthy drinking over time. The experience of pain has  also been shown to be associated with poorer responses to alcohol interventions. Primary care  physicians face a number of challenges when attempting to treat co-occurring unhealthy  drinking and pain among their patients. Pain management and reduction of alcohol use among  those who engage in heavy alcohol use is often not adequately achieved with pharmacological  treatments nor are pharmacological treatments indicated for common pain conditions. Moreover,  despite the availability of evidence-based psychosocial interventions for unhealthy drinking  and chronic pain, patients with each of these conditions typically show poor adherence to  treatment. Given the rates of pain and unhealthy alcohol use among primary care patients and  their impact on functioning and medical outcomes, there would be considerable benefit to an  accessible, easily utilized, integrative approach to treat heavy alcohol use and pain that  can be readily incorporated into the primary care setting. The objectives of this study are  to develop a smartphone-based intervention for reducing heavy alcohol use and pain in primary  care patients, determine the feasibility of implementing this intervention in the primary  care setting, provide effect size estimates of the intervention on outcomes, and develop  procedures to conduct a Stage II efficacy trial. Inclusion Criteria:  -  1 heavy drinking: defined as either [1] an average of more than 7(for women)/14 (for  men) standard drinks per week over the past month or [2] one or more heavy drinking  episodes (4+ standard drinks for women, 5+ standard drinks for men)  -  2 chronic pain: defined as non-cancer related pain of at least 3 months duration rated  as moderate or greater (past week pain severity rating of 4 or greater on the BPI  severity item) Exclusion Criteria:  -  psychoactive medication for pain or alcohol use for fewer than 2 months  -  history of bipolar disorder or schizophenia  -  current expressed suicidal intent  -  prior history of alcohol withdrawal related seizures or delirium tremens  -  behavioral treatment for pain or alcohol use in the past 3 months  -  any scheduled surgery within the next 6 months or acute life threatening illness that  requires treatment

This is an observational study, in which newborn infants from the general population are  screened at birth for HLA-conferred susceptibility to type 1 diabetes and celiac disease. The  participants carrying genetic susceptibility to type 1 diabetes (approximately 9.5%) will be  analyzed for diabetes-associated autoantibodies at the age of 1, 2 and 3 years, while those  predisposed to celiac disease (about 14%) will be screened for tissue transglutaminase  antibodies at the age of 1 and 3 years. The intention is to screen annually 10,400 newborn  infants for a period of 3 years. About 988 infants are each year identified as a child at  risk for type 1 diabetes, and it is expected that around 80% of the families with such a  child are willing to join the autoantibody screening. Approximately 1456 infants are each  year recognized as a child at risk for celiac disease, and again the expectation is that 80%  of the families will join the antibody screening program. The aim of the BABYSCREEN project is to identify newborn infants with HLA-conferred  susceptibility to T1D and/or CeD from the general population and to observe such children for  the appearance of disease-associated autoantibodies and clinical disease up to the age of 1-3  years. The plan is to screen all infants with maternal consent born in one of the two  delivery hospitals in the metropolitan Helsinki area, i.e. Women's Hospital in Helsinki and  Jorvi Hospital in Espoo. The parents to be will be informed about the study and invited  during pregnancy to take part in the study after the birth of their baby. The pregnant woman  is asked to give her electronic consent to participation through the Women's website  (https://www.terveyskyla.fi/naistalo) or a written informed consent on paper after both  parents have acquainted themselves with the study. The only inclusion criterion will be  informed consent signed by the mother.  The screening activity will be carried out over a 3-year period. The annual number of births  in the Helsinki region is about 13,000. It is expected that at least 80% of the parents will  give their informed consent to participation in the study. Accordingly about 31,200 newborn  infants would be screened for genetic susceptibility to T1D and CeD. The following HLA  genotypes represent those predisposing to T1D: (i) the high-risk genotype  (DR3)-DQA1*05-DQB1*02/DRB1*04:01/2/4/5;)-DQA1*03-DQB1*03:02; (ii) the moderately  increased-risk genotype DRB1*04:01/2/5-DQA1*03-DQB1*03:02/neutral haplotype; (iii) the  slightly increased-risk genotype (DR3)-DQA1*05-DQB1*02/ (DR9)-DQA1*03-DQB1*03:03; (iv) DR4  homozygosity DRB1*04:01/2/4/5)-DQA1*03-DQB1*03:02/DRB1*04:01/2/4/5)-DQA1*03-DQB1*03: 02; and  (v) DR3 homozygosity (DR3)-DQA1*05-DQB1*02/(DR3)-DQA1*05-DQB1*02. To cover those with genetic  susceptibility to CeD also all other genotypes including the DR3-DQ2 haplotype will be  identified. Their proportion among Finnish infants is 14%. This screening protocol  identifying 23.5% of the screened infants as at-risk children has a sensitivity of 64.6% for  T1D and more than 90% for CeD. Around 9.5% will carry HLA susceptibility to T1D and an  additional 14% predisposition to CeD. With an expected consent rate of 80%, approximately 988  participants with HLA-defined predisposition to T1D (about 370 of them having also  susceptibility to CeD) and 1,456 participants with HLA-conferred susceptibility to only CeD  would be ended up each year. In addition, DNA will later be extracted from cord blood to  identify genes outside the HLA gene region conferring increased risk for T1D and/or CeD.  Families with a baby carrying a predisposing HLA genotype are invited to follow-up for the  appearance of predictive autoantibodies. The participants genetically at risk for T1D will be  screened with the guardians' consents annually for four diabetes predictive autoantibodies  and followed up to 1-3 years of age. If a participant tests positive for one or more  autoantibodies at a given age, he/she will be invited for a second sample within 2 months  from the first positive sample. If a child test positive for multiple (≥ 2) autoantibodies,  HbA1c will be analyzed and an oral glucose tolerance test carried out to diagnose or exclude  dysglycemia. Dysglycemic participants will be referred to a pediatric unit taking care of  children with T1D for continued monitoring.  The participants at risk for CeD are screened for tissue transglutaminase antibodies (tTGA)  at the age of 1 and 3 years. If a child tests positive for such autoantibodies, endomysial  antibodies will be analyzed. Children testing positive for both autoantibodies will be  referred to a pediatríc gastroenterologist for consultation.  One objective of this project is to prevent diabetic ketoacidosis in those participants who  progress to clinical T1D and to diagnose early the development of CeD to prevent its  complications. This serves also as a demonstration project for the potential benefits  achieved with early population-based screening of two common chronic childhood disorders.  The following information will be collected from the participants in the screening study;  gestational age, route of delivery, gender, birth weight and length, head circumference, and  Apgar score. In addition, information on autoimmune diseases in family will be collected at  the beginning of the study and at the last study visit by electronic questionnaire, since any  autoimmune disease in the family increases the risk of T1D and/or CeD in other family  members. Growth will be monitored in the participants in the follow-up study.  Those at risk for T1D will be screened annually for the four biochemical autoantibodies  predicting T1D, i.e. insulin autoantibodies (IAA) and antibodies to glutamate decarboxylase  GADA), islet antigen 2 (IA-2A) and zinc transporter 8 (ZnT8A). These autoantibodies are  analyzed with specific radiobinding assays. If a participant tests positive for one or more  autoantibodies at a given age, he/she will be invited for a second sample within 2 months  from the first positive sample. Participants with confirmed positivity for multiple (≥2)  autoantibodies, will be invited for a new visit for assessing possible signs of dysglycemia.  A HbA1c sample is taken and a 2-hour oral glucose tolerance test will be carried out. If the  child has signs of dysglycemia, he/she will be referred to a pediatric unit taking care of  patients with T1D for contínued follow-up. Participants with confirmed positivity for T1D  associated autoantibodies at the last follow-up sample, will be invited to come to a new  visit for assessing T1D associated autoantibodies after 3 years.  The children predisposed to CeD will be analyzed for IgA and IgG class tTGA at the age of 1  or 1 and 3 years of age. If the child tests unequivocally positive for tTGA, the positive  sample will be analyzed for endomysial antibodies. If the participant has both  autoantibodies, she/he will be referred to a pediatric gastroenterologists for consideration  of duodenal biopsy. Participants with confirmed positivity for tTGA at the last follow-up  sample, will be invited to come to a new visit for assessing CeD associated autoantibodies  after 3 years. Inclusion Criteria:  -  mother has given an informed consent Exclusion Criteria:  -

This study wants to investigate whether exercise booster sessions applied in the follow-up  period after an exercise intervention can increase the sustainability of exercise induced  effects in persons with multiple sclerosis.  The study will be a randomized, multi-site, controlled trial. Participants will from the  beginning be allocated to either aerobic training group, resistance training group or control  group. After a 12 week exercise intervention, the exercise groups will be additionally  randomized to receive either exercise booster sessions + standard care or just standard care  in the 40 week follow up period.  It is hypothesized that exercise booster sessions can increase the sustainability of exercise  induced effects. MS is a chronic, autoimmune, and inflammatory disease of the central nervous system,  exemplified through marked demyelination and axonal loss. As a result, symptoms such as  fatigue, numbness, weakness, depression, walking difficulties and spasticity frequently  appear.  Although there is no cure for MS, several disease-modifying therapies are available. These  can potentially slow the progression of disabilities and reduce the overall disease burden.  This is of great interest from both an individual perspective, where increased disability is  associated with a lowered health-related quality of life, and from a societal perspective,  where increased disability is associated with larger costs.  Over the past decades exercise has been shown to be safe, tolerable and beneficial in persons  with MS (PwMS). Hence, it is known to be an effective way of treating symptoms such as  fatigue7, muscle weakness, walking impairments and depression. As with other chronic  diseases, exercise for PwMS has been proposed as "medicine". However, in order to benefit  from the positive effects of any kind of treatment (i.e. most medical drugs or exercise) one  has to adhere to the prescriptions of the treatment (i.e. dose and timing). Despite all the  potential benefits of exercise therapy for PwMS, one of the major challenges relate to  long-term maintenance of exercise efforts.  An emerging concept that may hold the potential to increase the sustainability of exercise  therapy is supervised "exercise booster sessions" (i.e. training sessions provided regularly  throughout the follow-up period, to sustain effects of the preceding exercise intervention).  These can be placed regularly during the follow-up period, where patients attend a number of  supervised high-intensity exercise sessions, hereby trying to boost the effects of the  preceding exercise intervention. Furthermore, exercise booster sessions can potentially  motivate the patient to keep exercising throughout the follow up period.  However, the optimal way of utilizing this concept is still not fully understood, and has not  yet been tried in neurological patients.  Therefore, the main purpose of the present study is to investigate how exercise booster  sessions combined with usual care performed over a period of 40 weeks affects the  sustainability of effects on functional capacity induced by a 12-week exercise intervention.  It is hypothesized that participants receiving exercise booster sessions + usual care during  follow up will have a better functional capacity at follow up, than the participants  receiving usual care only.  The study will be a randomized, multi-site, controlled trial. Participants will from the  beginning be allocated to either aerobic training group, resistance training group or control  group. After a 12 week exercise intervention, the exercise groups will be additionally  randomized to receive either exercise booster sessions + standard care or just standard care  in the 40 week follow up period.  The 12 week exercise intervention will consist of 2-3 weekly supervised exercise sessions.  The training will be planned by exercise physiologists and performed in a progressive manner.  To allow handling of a large number of participants, who is also geographically spread, the  exercise intervention will be locally anchored, but at the same time supervised by student  employees and controlled by internet- and telephonic communication.  Participants allocated to exercise booster sessions will receive two sessions every fifth  week during the follow up period.  The power calculation is based on the primary purpose of the study which is to investigate  the effect of frequently applied exercise booster sessions. To set the estimated number of  participants, a two-sample two-sided power calculation has been conducted. Based on previous  studies, a mean difference on functional capacity between the group receiving usual care and  the group receiving exercise booster sessions + usual care, regardless of exercise  intervention, is expected to be 6% with a standard deviation (SD) of ±10%.  The level of significance was set as 5% and a statistical power of 80%. According to the  power calculation each group shall contain 60 participants (expected drop-out rate of 30 % is  included).  The results of these studies can have great clinical implications in many ways. If we find  that by adding exercise booster sessions in a follow up period, one can maintain, or maybe  even improve, functional capacity over a long period, this would be a novel finding making  ground for new rehabilitation opportunities Inclusion Criteria:  -  A definite diagnosis of MS, according to the McDonald criteria  -  Walking <650m on 6MWT.  -  Exercising ≤ two sessions per week of moderate-to-high intensity during the past six  months. Exclusion Criteria:  -  Comprise comorbidities (cardiovascular-, respiratory-, orthopedic- or other  neurological diseases.)

The aim of this study is to determine whether motor imagery training during the  immobilisation period in patients with a distal radius fracture, results in an improved  functional outcome compared to patients who do not perform motor imagery. Rationale: Distal radius fracture (DRF) is a common injury that may lead to prolonged  function restrictions, decreased range of motion, reduced grip strength and pain. These  symptoms may be caused by physical changes due to the injury and/or by the 4-6 weeks  immobilization that is part of the conservative treatment. However, it might also be that  neural changes during the immobilization play an important role. Such changes might be  prevented by motor imagery training during the immobilization period. So, when neural changes  are prevented, this may lead to a better functional outcome.  Objective: The objective is to improve the functional outcome in distal radius fracture  patients, specified as an increase in function, dexterity, grip strength, range of motion,  and decrease of pain.  Study design: Parallel group randomized controlled trial, with a post-test only control group  design. Patients in the experimental group perform motor imagery training during the  immobilization period, in addition to the regular treatment. Patients in the control group  receive regular treatment.  Study population: Female DRF-patients who are conservatively treated by a cast, aged 45-75  years. The fracture must be a low energy trauma caused by a fall. Patients with a score  higher than 72 on the Vividness of Motor Imagery Questionnaire (VMIQ) are excluded, as well  as patients with co-morbidities that might influence the wrist function, or motor  imagery-ability, and patients with no understanding of Dutch language. The patients are  randomly allocated to the experimental or control group by restricted randomization to ensure  equal group sizes.  Intervention: Motor imagery training during the immobilization period).  Main study parameters/endpoints: The main study parameter is function. Secondary study  parameters are dexterity, range of motion, grip strength, and pain. Inclusion Criteria:  -  female patients  -  non-comminutive distal radius fracture  -  45 to 75 years of age Exclusion Criteria:  -  distal radius fracture caused by HET  -  comorbidities possibly influencing wrist function  -  comorbidities possibly influencing motor imagery ability  -  score higher than 72 on the Vividness of Motor Imagery Questionnaire

This is a single-center, open-label, single-arm study to evaluate the primary safety and  efficacy of autologous anti-CD7 chimeric antigen receptor(CAR)-modified T cells(CAR7-Ts) in  patients with relapsed or refractory T lymphoid malignancies. Chimeric antigen receptor-T cells (CAR-T) have made breakthroughs in the treatment of B-cell  tumors, especially refractory/relapsed acute B lymphocytes. CD7 is a transmembrane  glycoprotein expressed by T cells and natural killer cells and their precursors; it is also  expressed in >95% of lymphoblastic T-cell leukemias and lymphomas . CD7 was previously  evaluated as a target for immunotoxin-loaded antibodies in patients with T-cell malignancies,  but tumor responses were limited.  Enhancing the potency of CD7-directed cytotoxicity by substituting autologous CAR-T cells for  a monoclonal antibody would augment the efficacy of CD7-targeted therapy in patients with  T-cell malignancies. To prepare CAR7-T cells, CD7 expression is suppressed on autologous T  cells by unique blocking technique, and CD7-negative T cells are transduced with a humanized  anti-CD7-41BB-CD3ζ lentiviral vector.  This is an investigational study. The objectives are to evaluate the safety and efficacy of  CAR7-T cells in patients with CD7+ T-cell malignancies. Inclusion Criteria:  1. Aged ≥ 18 years;  2. Expected survival over 60 days;  3. Eastern Cooperative Oncology Group score 0-2;  4. Diagnosed as T-cell hematologic malignancies (including leukemia and lymphoma)  according to WHO2016 criteria;  5. Patients must relapse or be refractory after at least two lines of therapy.  6. CD7 were positive in bone marrow by immunohistochemistry or flow cytometry at  screening, and one of the following conditions is satisfied: A. No remission was  achieved after at least 2 lines of standard therapy; B. Relapse or progression after  standard treatment; C. Relapse after autologous or allogeneic hematopoietic stem cell  transplantation;  7. Have no fertility requirements or plans for one year since enrolment in this clinical  trial;  8. Patient or his or her legal guardian voluntarily participates in and signs an informed  consent form. Exclusion Criteria:  1. Complicated with central system leukemia/lymphoma;  2. Existing or preexisting CNS conditions, such as epileptic seizures, cerebrovascular  ischemia/hemorrhage, dementia, cerebellar disease, or any CNS related autoimmune  disease;  3. Symptomatic heart failure or severe arrhythmias;  4. Symptoms of severe respiratory failure;  5. Complicated with other types of malignant tumors;  6. Serum creatinine and/or urea nitrogen ≥ 1.5 times of normal value;  7. Suffer from sepsis or other uncontrollable infections;  8. Intracranial hypertension or brain consciousness disorder;  9. Severe mental disorders;  10. Have received organ transplantation (excluding bone marrow transplantation);  11. Female patients (fertile patients) had positive blood HCG test;  12. Hepatitis (including hepatitis B and C), AIDS and syphilis were screened positive;  13. Patients with graft-versus-host disease (GVHD) or who require immunosuppressant  treatment;  14. The absolute value of lymphocytes was too low to manufacture CART cells;  15. Other conditions considered inappropriate by the researcher.

This is a randomized, double-blind, placebo-controlled, multiple-center study, to assess the  efficacy and safety of Cannabidiol administered as ZYN002 for the treatment of children and  adolescent patients with Fragile X Syndrome (FXS). Eligible participants will participate in  up to an 18 week treatment period, where all participants will receive placebo or active  study drug. Patients ages 3 to < 18 years, will be eligible to participate. This is a randomized, double-blind, placebo-controlled, multiple-center study, to assess the  efficacy and safety of ZYN002, a pharmaceutically manufactured cannabidiol, formulated as a  clear gel that can be applied to the skin (called transdermal delivery), in children and  adolescents with FXS. 204 male and female patients, ages 3 to < 18 years, will be randomized  1:1 to either trial drug or placebo and will undergo a 18-week treatment period.  Randomization will be stratified by gender, methylation status and weight. The study will be  comprised of a Screening visit and a combination of seven visits both onsite (face-to-face)  and virtual. The assignment of study drug or placebo will be done by a computer generated  system and neither the study doctor, participant or their caregivers will know which  treatment is being given to them. The dose of the treatment will depend on the weight of the  participants. If the participants weigh less than or equal to 30 kg, they will receive 2  sachets of the gel per day (1 sachet approximately every 12 hours). If the participant weighs  more than 30 kg but less than or equal to 50 kg, they will receive 4 sachets of gel per day  (2 sachets approximately every 12 hours). Participants who weigh more than 50 kg will receive  6 sachets of gel per day (3 sachets approximately every 12 hours). Parents/ caregivers will  be instructed on proper application of the gel. The gel will be applied to clean, dry, intact  skin of the upper arms/ shoulders.  Blood samples will be collected for safety analysis of ZYN002. An independent analytical  laboratory will also perform CGG repeat and methylation status analyses. Additionally, the  parents/caregivers and study doctor will be asked to complete some questionnaires for  efficacy and safety assessment. Inclusion Criteria:  -  Male or female children and adolescents aged 3 to < 18 years, at the time of  Screening.  -  Judged by the Investigator to be in generally good health at Screening based upon the  results of medical history, physical exam, 12-lead ECG and clinical laboratory test  results. -Laboratory results outside the reference range must be documented as not  clinically significant by both the Investigator and Sponsor.  -  Participants must have a diagnosis of FXS through molecular documentation of full  mutation of the FMR1 gene documented through genetic testing at Screening.  -  Patients with a history of seizure disorders must currently be receiving treatment  with a stable regimen of no more than two anti-seizure medications (ASMs) for the four  weeks preceding study Screening; or must be seizure-free for one year if not currently  receiving ASMs.  -  Patients taking psychoactive medication(s) should be on a stable regimen of not more  than three such medications for at least fours weeks preceding Screening and must  maintain that regimen throughout the study. Psychoactive medications include (but are  not limited to) antipsychotics, antidepressants, anxiolytics, attention-deficit /  hyperactivity disorder (ADHD) medications, and medications for sleep.  -  If patients are receiving non-pharmacological, behavioral and/or dietary  interventions, they must be stable and have been doing so for three months prior to  screening.  -  Patients have a body mass index between 12-30 kg/m2 (inclusive).  -  Females of childbearing potential must have a negative serum pregnancy test at the  Screening Visit and a negative serum or urine pregnancy test at all designated visits.  -  Patients and parents/caregivers must be adequately informed of the nature and risks of  the study and given written informed consent prior to Screening.  -  Patients and parents/caregivers agree to abide by all study restrictions and comply  with all study procedures, and in the Investigator's opinion, are reliable and willing  and able to comply with all protocol requirements and procedures. Exclusion Criteria:  -  Females who are pregnant, nursing or planning a pregnancy; females of childbearing  potential and male patients with a partner of childbearing potential who are unwilling  or unable to use an acceptable method of contraception as outlined below for the  duration of therapy and for three months after the last dose of study medication.  Standard acceptable methods of contraception include abstinence (defined as refraining  from heterosexual intercourse from screening to three months after the last dose of  study medication) or the use of a highly effective method of contraception, including  hormonal contraception, diaphragm, cervical cap, vaginal sponge, condom, spermicide,  vasectomy, or intrauterine device. The reliability of sexual abstinence needs to be  evaluated in relation to the duration of the clinical trial and the preferred and  usual lifestyle of the subject. Periodic abstinence (calendar, symptothermal,  post-ovulation methods) is not an acceptable method of contraception.  -  History of significant allergic condition, significant drug-related hypersensitivity,  or allergic reaction to any compound or chemical class related to ZYN002 or its  excipients.  -  Exposure to any investigational drug or device less than or equal to 30 days prior to  Screening or at any time during the study.  -  Alanine aminotransferase (ALT), aspartate aminotransferase (AST) or total bilirubin  levels greater than or equal to 2 times the upper limit of normal or alkaline  phosphatase levels greater than or equal to 3 times the upper limit of normal.  -  Use of cannabis or any THC or CBD-containing product within 3 months of Screening  Visit or during the study (aside from ZYN002).  -  Patient has a positive drug screen, including ethanol, cocaine, THC, barbiturates,  amphetamines (unless prescribed), benzodiazepines (except midazolam or comparable  administered for blood draws and ECG collection), and opiates.  -  Patient is using the following AEDs (medications for the treatment of seizures and/ or  epilepsy): clobazam, phenobarbital, ethosuximide, felbamate, carbamazepine, phenytoin,  or vigabatrin.  -  Patient is using a strong inhibitor/inducer of CYP3A4 or sensitive substrate of CYP3A4  including but not limited to the following medications: midazolam (except single doses  administered for the purposes of obtaining blood samples and ECG's), oral  ketoconazole, fluconazole, nefazadone, rifampin, alfentanil, alfuzosin, amiodarone,  cyclosporine, dasatinib, docetaxol, eplerenone, ergotamine, everolimus, fentanyl,  halofantrine, irinotecan, lapatinib, levomethadyl, lumefantrine, nilotinib, pimozide,  quinidine, ranolazine, sirolimus, tacrolimus, temsirolimus, toremifene, tretinioin,  vincristine, vinorelbine, St. John's Wort, and grapefruit Juice/products.  -  Patients may not be taking any benzodiazepines (except single doses administered for  the purposes of obtaining blood samples and ECGs) at screening or throughout the  study.  -  Patient is expected to initiate or change pharmacologic or non-pharmacologic  interventions during the course of the study.  -  Patient has an advanced, severe, or unstable disease that may interfere with the study  outcome evaluations.  -  Patient has acute or progressive neurological disease, psychosis, schizophrenia or any  other psychiatric disorder or severe mental abnormalities (other than FXS) that are  likely to require changes in drug therapy or interfere with the study objectives or  ability to adhere to protocol requirements.  -  Patient has a positive result for the presence of HBsAg, HCV, or HIV antibodies.  -  Patient has known history of cardiovascular disease, advanced arteriosclerosis,  structural cardiac abnormality, cardiomyopathy, serious heart rhythm abnormalities,  coronary artery disease, cardiac conduction problems, exercise-related cardiac events  including syncope and pre-syncope, risk factors for Torsades de pointes (TdP) (e.g.,  heart failure, hypokalemia, family history of Long QT Syndrome), or other serious  cardiac problems.  -  Any clinically significant condition or abnormal findings at the Screening Visit that  would, in the opinion of the Investigator, preclude study participation or interfere  with the evaluation of the study medication.  -  Any skin disease or condition including eczema, psoriasis, melanoma, acne, contact  dermatitis, scarring, imperfections, lesions, tattoos, or discoloration that may  affect treatment application, application site assessments or absorption of the trial  drug.  -  History of treatment for, or evidence of, drug abuse within the past year.  -  Previous participation in a ZYN002 study (with the exception of patients who were  screen failures in Study ZYN2-CL-016 and did not enter Study ZYN2-CL-017).  -  Patient responds "yes" to Question 4 or 5 on the C-SSRS (Children) during Screening or  at any time on study.

Prolonged mechanical ventilation has been defined as the need for >21 days. The muscle  weakness occurred most commonly in patients with PMV and resulted in increasing time to wean  from mechanical ventilation, and longer stay in hospital.  Neuromuscular electrical stimulation (NMES) involves applying a stimuli to skeletal muscle,  to trigger muscle contraction, and it can be used for the recovery of muscle mass and muscle  strength following prolonged immobilization. NMES also improve microcirculation and systemic  circulation in patients with cardiopulmonary diseases.  The purposes of this study:  1. to examine the acute effects of NMES on the microcirculation, physiologic response and  metabolic demand in patients with PMV.  2. to investigate the training effects of NMES on microcirculation, muscle strength and  weaning outcomes in patients with PMV.  METHODS: Subjects with PMV are recruited and are randomly assigned into NMES (n=20) or  control group (n=20).The NMES group receive daily NMES for 30 min/session for 10 days. The  assessment of muscle strength and weaning profile were performed before and after  intervention. During the first and the last NMES session, the status of microcirculation and  local muscle tissue oxygenation will be measured by NIRS, and the metabolic status will be  measured by IC. The ventilator weaning rate and length of stay in RCC will be recorded. Scientific and technologic advances in medicine have resulted in the ability of the medical  team to prolong life. One consequence of life-extending advancements in technology is the  increasing numbers of patients requiring prolonged mechanical ventilation (PMV). Prolonged  mechanical ventilation has been defined as the need for 21 days, of consecutive mechanical  ventilation for six hours/day. The interaction of underlying diseases and prolong bedridden  result in various complication in patients with PMV. Known complications can include: muscle  weakness, atelectasis, and deconditioning. The muscle weakness occurred most commonly in  patients with PMV and resulted in increasing time to wean successfully from mechanical  ventilation, and longer stay in hospital. Exercise is effective in improving muscle strength  and physical function in patients with heart failure and chronic obstructive pulmonary  disease (COPD. However, patients with PMV may be too fragile to perform excise. Neuromuscular  electrical stimulation (NMES) involves applying a series of stimuli to skeletal muscle,  primarily to trigger muscle contraction, and it can be used for the recovery of muscle mass  and muscle strength following prolonged immobilization. NMES also improve microcirculation  and systemic circulation in patients with cardiopulmonary diseases. In addition, the  application of NMES increases oxygen consumption of whole body and elicits physiologic  effects that are similar to aerobic exercise. However, the effects of NMES on the PMV  population remain unclear. Near-infrared spectroscopy (NIRS) is a recently developed  noninvasive method of measuring tissue oxygenation, blood flow, and local tissue metabolism.  NIRS combined with a vascular occlusion test is proposed as a tool to assess the  microvascular response. Indirect calorimetry (IC) uses the method of breath-bybreath  monitoring by pneumotachography to measure oxygen consumption (VO2) and carbon dioxide  production (VCO2).  The purposes of this study:  1. to examine the acute effects of NMES on the microcirculation, physiologic response and  metabolic demand in patients with PMV.  2. to investigate the training effects of NMES on microcirculation, muscle strength and  weaning outcomes in patients with PMV. METHODS: Subjects who have been on ventilator  for>= 21 days are recruited form respiratory care center (RCC) and are randomly assigned  into NMES (n=20) or control group (n=20).The NMES group receive daily NMES for 30  min/session for 10 days. The assessment of muscle strength and weaning profile were  performed before and after intervention. During the first and the last NMES session, the  status of microcirculation and local muscle tissue oxygenation will be measured by NIRS,  and the metabolic status will be measured by IC. The mechanical ventilator weaning  outcomes and length of stay in RCC will be recorded. The results of this study help us  to confirm whether the application of NMES is beneficial in the improvement of muscle  strength in patients with PMV, and to furtherly understand the mechanisms. The results  may provide an alternative options for clinicians functional and hospitalization  outcomes in patients with PMV. Inclusion Criteria:  1. age ≧ 20 years;  2. MV for > 6 h/day for > 21 days; and  3. medical stability, absence of signs and symptoms of infection, and hemodynamic  stability).  4. hemodynamic stable without or with a low dose of vasopressor ((Dopamine or Dobutamine  <5μg/kg/min) Exclusion Criteria:  1. acute lung or systemic infection,  2. ongoing neuromuscular disease (e.g., myasthenia gravis, Guillain-Barre disease)  3. bone contracture or skin lesion  4. obesity [body mass index (BMI) >35 kg/m2].  5. disease at end-stage with expecting survival <=6month  6. pregnancy  7. severe edema (deep indentation when pressing a finger into the skin, requiring >30 s  to rebound

Due to different study designs, the sponsor separated Part C into this separate registration  (NCT04958642), leaving Parts A/B in NCT02534844. The trial's final results for the primary  outcome measure of Adverse Events (AE) will be reported here.  The primary and study completion dates are based on the anticipated last date safety data  will be collected from Part C participants.  This study is to evaluate how safe and effective adrabetadex is for participants with  Niemann-Pick Type C1 (NPC1) disease who experience neurologic symptoms (listed under  Keywords).  In Parts A/B (NCT02534844), two out of every three participants will receive the study drug.  The third participant will receive 1 to 2 small needle pricks at the location where the IT  injection is normally made (sham control).  In Part C, all participants will receive study drug. Participants in Part C will receive adrabetadex until the investigator considers adrabetadex  to no longer be beneficial to the participant, or the development program is discontinued. Inclusion Criteria:  One of the following is required for inclusion into VTS301 Part C:  -  Has agreed to convert from the monthly dosing regimen used in the NIH phase 1/2a  protocol to an every 2 weeks dosing regimen  -  The investigator has received prior written authorization from the sponsor for the  participant to enter VTS301 Part C on an amended dose and/or regimen  -  Has received prior written authorization from Vtesse to enroll directly into Part C Exclusion Criteria:  -  None of the inclusion criteria are applicable

Conventional monopolar or bipolar transurethral resection of bladder tumors is the most  common method for resection of a bladder mass. En bloc resection has demonstrated success in  the literature utilizing different techniques and lasers, including utilizing the Ho:YAG and  Tm:YAG lasers. A recent metanalysis revealed several benefits to laser en bloc resection  including less complications and lower recurrence rate.22 Subsequently, laser technology has  also advanced with the development of a super pulsed TFL which overcomes many limitations of  prior traditional lasers. Olympus' SOLTIVE™ TFL, which has demonstrated improved  maneuverability and control, has a shallow depth of tissue penetration at 0.15mm leading to  precise resection and optimal hemostasis. Despite these beneficial characteristics and  qualities along with the promising utility of en bloc resection, the Olympus SOLTIVE™ TFL has  not been described in en bloc resection of bladder tumors. The investigator seek to determine  if the proposed benefits of this device can be realized both pathologically and clinically in  en bloc resection of bladder tumors. This is a prospective study investigating the use of the SOLTIVE™ Thulium Super pulse laser  for the treatment of bladder tumors via en bloc resection in patients who present for  treatment at the University of Kansas Health System. The study pretreatment evaluation and  follow up schedule are the same as used routinely in daily practice, in accordance with  standard of care practices. Routine labs (e.g. complete blood count, basic or complete  metabolic panel, urinalysis and urine culture), and imaging will be obtained as per standard  care at the provider's discretion based on the patient's history and physical exam.  A prospective data collection of the patients with bladder cancer undergoing en bloc  resection will be conducted in this study.  A complete medical, surgical and bladder cancer history will be obtained by the surgical team  in the pre-operative setting, per standard of care practices.  Patients will be taken to the operating room per standard of care for resection of one or  more bladder tumors. The SOLTIVE™ Super Pulsed Thulium laser will be utilized for resection  of the tumors in an en bloc fashion.  Technique for en bloc resection of bladder tumor Tumor marked with a circular coagulation  blockage border approximately 1.0 cm away from the edge. All visible vessels around the tumor  will be coagulated and lasered before the incision to reduce bleeding. Along this mark, a  fan-shaped incision into the bladder wall is made until the muscle layer is visible uplift  tumor by the force of the irrigation and use of the laser tip, gradually exposing the tumor  base tumor base is disconnected tumor is then removed en bloc. If it is unable to be removed  through the resectoscope in one piece due to its size, it may be cut into 2 pieces at the  surgeon's discretion.  At the surgeon's discretion, the procedure may be converted to a traditional TURBT utilizing  either monopolar or bipolar loop electrocautery. Other intraoperative/postoperative decisions  based on surgeon discretion and standard of care treatment:  Each specimen will be collected and sent en bloc to the pathology department. Ameer Hazma,  MD, a genitourinary pathologist, will review all specimens to decrease interobserver  variation.  Urinary symptoms before and after the procedure will be evaluated. This will be assessed via  an electronic questionnaire that will be sent to study participants. Symptoms will be  evaluated pre-operatively the morning of surgery as well as on post-operative day #3, 7, and  14.  No validated questionnaire for evaluation of urinary symptoms after bladder tumor resection  currently exists. From clinical experience, the symptoms patients most commonly report  include frequency, urgency, dysuria, or hematuria. The investigator will therefore modified  the existing American Urological Association's Symptom score to address these symptoms on a  shorter term basis. Inclusion Criteria:  1. Patients must be 18 years of age or older.  2. Patient presenting for resection of papillary bladder tumor visualized on cystoscopy  1. New bladder tumor  2. Recurrent tumors  3. Tumor <3cm Exclusion Criteria:  1. Patient unwilling to undergo en bloc resection  2. Non papillary lesions/tumors

This study aims to evaluate the efficacy of an endoluminal gastric plication using an  endoluminal-suturing device to improve severe OSAS in patients with a BMI above or equal to  28 kg/m² until 34.9kg/m². Obesity is one of the most critical public health burdens worldwide. Its prevalence is  increasing, as well as its comorbidities. The main comorbidity of obesity on the respiratory  system is the obstructive sleep apnea syndrome (OSAS). The prevalence of OSAS in the obese  population is around 45%. OSAS increased cardiovascular risk and decreased quality of life.  The most alterable risk factor of OSAS is obesity. Therefore, weight loss is the cornerstone  of the treatment. There is some evidence of the efficacy of weight loss surgery (lap band,  sleeve gastrectomy, biliary pancreatic deviation, duodenal switch, and Roux-and-Y-gastric  bypass) to improve OSAS. Current recommendations suggest bariatric surgery management for  patients with a BMI > 35kg/m2 and OSAS. However, most studies have limited scientific value  (retrospective observational trials), and the follow-up of patients is limited, mainly due to  patients' inadequate compliance. Moreover, until now, there is no reliable predictor for the  percentage of reduction of AHI caused by weight loss. On the other hand, there is no approved  treatment in patients presenting a BMI between 28 kg/m² to 34.9kg/m² and OSAS.  Endoscopic endoluminal approaches to address obesity have become an important topic of  interest over the past decade. Endomina® (Endo Tools Therapeutics, Gosselies, Belgium) is a  novel restrictive endoluminal approach. This new procedure permitted a weight loss of 29 % on  average sustained at one year. This technique was not yet evaluated in patients with 28 kg/m2  ≤ BMI ≤ 34.9/m2 to improve OSAS.  The current feasibility study aims to evaluate the efficacy of an endoluminal gastric  plication using an endoluminal-suturing device to improve severe OSAS in patients with above  or equal to 28 kg/m², BMI until 34.9kg/m². Inclusion Criteria:  -  Age between 18-65 years  -  BMI between 28 to 34.9 kg/m²  -  AHI ≥ 30 events/hour  -  De novo CPAP user, installed within 2 months prior enrollment  -  Must be able to comply with all study requirements for the duration of the study, as  outlined in the protocol. This includes complying with the visit schedule as well as  study-specific procedures such as clinical assessment, endoscopy, radiography, as well  as laboratory investigations  -  Must be able to understand and be willing to provide written informed consent;  -  Had followed the multidisciplinary bariatric workup (blood analyses, dietician,  psychologist and doctor appointments) Exclusion Criteria:  -  Presence of an obesity-hypoventilation syndrome defined as a PaCO2 ≥ 45 mmHg without  any other respiratory disease.  -  CPAP treatment failure defined as central sleep apnea occurrence under CPAP treatment  or a residual AHI > 5 under optimal CPAP treatment.  -  Incompliance to cPAP treatment defined as an observance to cPAP of at least 4 hours  per night in average.  -  Achalasia and any other esophageal motility disorders  -  Current severe esophagitis (grade C and D based on Los Angeles Classification)  -  Current Gastro-duodenal ulcer  -  Heart diseases: unstable angina, myocardial infarction within the past year, or heart  disease classified within the New York Heart Association's Class III or IV functional  capacity;  -  Hypertension: uncontrolled hypertension during the last 3 months;  -  Diabetes: uncontrolled diabetes (on insulin therapy or oral therapy with Hba1c > 10%);  -  TBWL >5% over the last 6 months  -  Current severe renal, hepatic, pulmonary disease or cancer;  -  Current gastrointestinal stenosis or obstruction  -  Pregnancy, breastfeeding or willing to become pregnant in the coming 18 months  -  Bariatric surgery, balloon or other endoscopic obesity-related therapy within 6 months  of enrollment in this study  -  Anticoagulant therapy  -  Impending gastric surgery 60 days post-intervention  -  Psychiatric disorder refuted after psychological evaluation

This study is designed to test the effectiveness of a psychoeducation-based program to  address communication and conflict resolution in families, thereby supporting mental health  in children and their caregivers. The goal of the study is to evaluate the effectiveness of a program to improve mental health  in families by reducing stress and supporting effective communication and conflict  resolution.  Families will be randomly assigned to one of two conditions: in the self-study condition,  families will receive information to review on their own, paired with regular (weekly)  contact from a family coach; in the second condition, families will receive information to  review on their own, regular contact from a coach, and will participate in video sessions  with a family coach who will provide feedback on their interactions and coaching on their use  of a communication technique. Data collection, management and analysis will be conducted by  researchers at the University of Notre Dame, but the intervention will occur through  community organizations in three cities in Indiana, allowing for tests of the effectiveness  of the program when it is implemented in community settings. Families will participate in a  pre-test assessment, a four-week intervention, a post-test assessment, and a one-year follow  up assessment. Also evaluated will be organizational factors and factors that impact ultimate  implementation and scalability of the program in community settings. Inclusion Criteria:  -  Two parents or primary caregivers  -  Child between 4 and 17 years old  -  English literate  -  Able/willing to participate through the 12-month follow up assessment. Exclusion Criteria:  -  Families who cannot communicate in English  -  Single parent families

Either PRP or HA is each effective for treating knee OA. However, the efficacy of combined  PRP and HA injections remains unknown clinically. Intraarticular plasma-rich platelet (PRP) or hyaluronic acid (HA) was each effective for knee  osteoarthritis(OA). The efficacy of combined injections remains unknown. This study aimed to  evaluate the efficacy of PRP combined with different hyaluronan for treating knee OA. In a  prospective, randomized-controlled trial, 95 patients with Kellgren-Lawrence grade 2 knee OA  were randomized to receive a single intraarticular Artz (10mg/ml) followed by PRP (N=48) into  target knee or single HYAJOINT Plus (20mg/ml) injection followed by PRP (N=47). Primary  outcome was the change from baseline in the visual analog scale (VAS) pain at 6 months.  Secondary outcomes included the Western Ontario and McMaster Universities Osteoarthritis  Index (WOMAC), Lequesne index, single leg stance test (SLS), use of rescue analgesics and  patient satisfaction. Inclusion Criteria:  -  Age of 20-85 years Symptomatic knee osteoarthritis for more than 6 months despite  analgesics, NSAIDs, or physical therapy Kellgren-Lawrence grade-2 knee osteoarthritis  seen on radiographs made within previous 6 months Radiological evidence of bilateral  knee OA was accepted if global pain VAS in the contralateral knee was less than 30 mm. Exclusion Criteria:  -  Previous orthopedic surgery on spine or lower limb Disabling osteoarthritis of either  hip or foot Knee instability, apparent joint effusion, or marked valgus/varus  deformity Known allergy to avian proteins or hyaluronan products Confirmed or  suspected pregnancy, or lactating Intra-articular injections into knee in previous 6  months Any specific medical conditions (rheumatoid arthritis, active infection,  hemiparesis, neoplasm, hematological etc.) that would interfere with assessments

The inflammatory bowel diseases (IBDs), ulcerative colitis (UC) and Crohn's disease (CD), are  characterized by lifelong relapsing-remitting gastrointestinal inflammation, with symptoms of  abdominal pain, diarrhea, and rectal bleeding during active disease. Medical therapy reduces  intestinal inflammation and ameliorates symptoms. Clinical remission is defined when symptoms  are resolved. In these periods, patients are able to perform daily activities more freely and  lead a normal lifestyle. Biochemical remission (normalization of CRP and fecal Calprotectin)  and endoscopic remission (no visual signs of inflammation of the mucosa in endoscopy) are the  goals of IBD treatment.  Unfortunately, 30-40% of patients will relapse during 6 months from achieving remission. Risk  factors for disease exacerbation are still unknown, and no guidelines exist as to the  prevention of relapse and maintenance of remission in IBD patients.  In addition to the above, sleep disturbances and disturbances in the circadian rhythm can be  a potential cause of flare-up. Sleep disorders cause changes in immune function, which later  affect the course of the disease in IBD. This back affects the sleep pattern, so that a cycle  is created, which may perpetuate the inflammation.  The interactions between sleep and inflammation are complex. An effective immune system  affects sleep, and sleep disorders affect the functioning of the immune system. Furthermore,  changes in the biological clock and sleep deprivation have been directly shown to worsen  ulcerative colitis in laboratory animals. In people with sleep disorders, high levels of  inflammation were found.  However, it is difficult to dissect the cause and effect for these associations, given their  complex interactions.  Therefore we are planning to conduct a prospective study to assess variety of factors that  might be associated with the activity of IBD. Prospectively follow IBD patients in remission (both clinical and biochemical) until disease  exacerbation.  • Specific aims:  -  To detect risk factors and early signs for disease exacerbation in IBD patients.  -  To detect predictors of disease exacerbation from environmental and behavioral  characteristics of patients, clinical and biochemical characteristics of the disease.  -  To examine whether changes in circadian rhythm are associated with improvement in  clinical and biological disease activity  Study design:  -  A prospective cohort study. Eligible patients will be follow up for at least one year or  until relapse time.  -  Setting: prospectively collect clinical, behavioral, dietary and environmental data of  IBD patients currently declared in an endoscopic remission according to the criteria in  Israel. Data will be collected according to a uniform standardized protocol specifically  adapted to the needs of the study. The team will include members of the IBD clinic at  the Tel Aviv Medical Center, run by Dr. Nitsan Maharshak.  Study population:  Eligible IBD patients treated at the IBD clinic in the Tel Aviv Medical Center participating  in the study, which have signed an informed consent form and answered to all the study  inclusion criteria. Patients will be informed of the study by their treating physician,  recruited and followed throughout the follow-up period by study co-ordinators. Inclusion Criteria:  -  Patients diagnosed as suffering from Crohn's disease (CD), Ulcerative colitis (UC) or  Pouchitis for at least 2 months who are in clinical and biologic remission according  to Steroid free clinical remission for greater or equal to 3 months according to the  following activity index  -  Harvey Bradshaw index (HBI)<5 for CD patients  -  Simple Clinical Colitis activity index (SCCAI)≤2 for UC patients  -  Pouch disease activity index ≤6 / mPDAI ≤4 for Pouch patients  Also, patients will be included if they fullfull the following:  -  Age 18-80 years  -  Clinically stable patients, on constant medicinal regimen (mesalamine at least 4  weeks, or immunomodulators at least 12 weeks or biologics at least 12 weeks therapy,  medical cannabis at least 2 weeks before inclusion to the study) Exclusion Criteria:  -  • Inability to sign an informed consent and complete the study protocol  -  Steroid therapy during the past 3 months  -  Antibiotic therapy during the past 2 weeks  -  Unstable or uncontrolled medical disorder, and sever systemic disease (other than  IBD)  -  Participating in another clinical interventional trial  -  Stoma

The purpose of this study is to learn more about people with insomnia disorder and cognitive  impairment. Cognitive impairment is difficulty with mental abilities such as thinking,  knowing and remembering. Primary insomnia (PI) sufferers typically complain of such daytime impairments as reduced  attention, concentration, memory and global mental acuity. Moreover, epidemiological studies  have shown PI contributes to reduced productivity, work and traffic accidents, and serious  falls among the elderly. Despite such findings, laboratory-based efforts to corroborate the  cognitive complaints of PI sufferers have produced mixed results. Indeed, many studies  comparing PI sufferers with non-complaining normal sleepers across a range of  neuropsychological tests have failed to show any relative deficits among the PI group. Such  findings, in turn, has led to the impression that PI patients cognitive complaints may be  over-stated and result from their attentional bias toward minor cognitive errors,  dysfunctional beliefs about the impact of insomnia on functioning or excessive self focus  rather than to any measurable daytime impairment.  However, many previous such studies were underpowered due to small sample sizes and employed  neuropsychological tests designed for detecting impairment resulting from brain  disease/damage rather than the more subtle albeit significant impairments of which PI  patients complain. In recent research, we and others have shown that PI sufferers do, indeed,  show greater deficits (slower and more variable reaction times) particularly on complex  switching attention tasks. Moreover, there is some preliminary evidence that the subgroup of  PI sufferers with elevated levels of physiological hyperarousal are most prone to suffer from  neuro-cognitive performance deficits than are matched groups of PI sufferers who are not  physiologically hyperaroused and normally alert individuals without insomnia. For example,  Fernandez-Mendoza recently showed that PI sufferers with a hyperarousal pattern suggested by  their objective short sleep duration on serial polysomnograms (PSG) performed more poorly on  a complex switching attention task than did both normal sleepers and PI sufferers with normal  objective sleep durations.  In our efforts to follow up on this latter work, we recently examined the error rates of  alert and sleepy PI sufferers and normal sleepers across a series of simple and complex  reaction time tasks. We employed age and gender matched samples of PI (N=89) sufferers and  normal sleepers-NS (N=95). Participants underwent three nights of PSG followed by daytime  testing with a four-trial Multiple Sleep Latency Test-MSLT. The PI and NS groups were each  subdivided into "alert" (e.g., MSLT mean onset latency > 8 minutes) and "sleepy" (e.g., MSLT  mean onset latency < 8 minutes) subgroups to allow for testing the main and interaction  effects of participant type and level of alertness. "Alert" participants had longer MSLT  latencies than "sleepy" participants (12.7 vs. 5.4 minutes). PI sufferers had fewer correct  responses on performance testing than did NS. However, as shown by the adjacent, figure we  found a significant group x alertness interaction (p = .0013) with greater error rates  occurring among alert (hyperaroused) PI sufferers (Mean=4.5±3.6 errors per trial) than among  alert NS (Mean=2.6±1.9 errors per trial). This was particularly true for the more complex  switching attention task.  Our work along with that of Fernandez-Mendoza serve to confirm that PI sufferers have  measureable objective neuro-cognitive deficits and provide some preliminary suggestion for  the types of testing approaches that should be used to detect them. The identification of  tests sensitive to PI sufferers' cognitive deficits are particularly relevant for testing the  effects of current and future insomnia therapies on patients' objective daytime functioning.  Measures of daytime dysfunction can and should serve as endpoints for assessing benefits and  detriments of insomnia therapies. In addition, our recent work suggests that subgroups of PI  sufferers may differ in their daytime deficits, with those showing physiological hyperarousal  being most prone to make errors. This finding suggests that different types or doses of  treatment may be needed to reverse the daytime impairments of the hyperaroused and  non-aroused PI patients. However, our line of research would benefit by replication and  extension findings to (1) further confirm the detrimental effects of physiological  hyperarousal on PI sufferer's neuro-cognitive functioning; and (2) identify a broader range  of tests that can be used for assessing diurnal cognitive impairments in both physiologically  hyperaroused and lesser aroused PI groups. The current project will address these aims. Inclusion Criteria:  -  21 to 80 years of age  -  Insomnia sufferers enrolled, will meet Research Diagnostic Criteria for insomnia  disorder  -  score > 14 on the Insomnia Severity Index  -  report insomnia for > 3 months  -  have sleep difficulties > 3 nights per week  -  score < 3 on the Epworth Sleepiness Scale (ESS)  -  score > 40 on the Hyperarousal Scale and report an inability to nap in the daytime  -  The normal sleepers enrolled will report general satisfaction with sleep and no  sleep/wake complaints, score < 10 on the ESS, score < 35 on the Hyperarousal Scale,  and deny a practice of routine daytime napping Exclusion Criteria:  -  sleep-disruptive medical condition (e.g., rheumatoid arthritis)  -  current major psychiatric (Axis I) condition on the basis of a Structured Clinical  Interview for Psychiatric Disorders (SCID)  -  sedative hypnotic dependence and unwillingness/inability to abstain from these  medications while in the study  -  use of anxiolytics, antidepressants, or any other psychotropic medication  -  an apnea/hypopnea index (AHI) > 5 or a periodic limb movement-related arousal index >  5 during on screening PSG that includes a full sleep montage to allow for  detection/diagnosis of sleep-disordered breathing and Periodic Limb Movement Disorder  (PLMD).  -  female participants who have tested positive on urine pregnancy tests or planing on  becoming pregnant during the study  -  Additionally, self-described NS who meet criteria for any sleep disorder and those  insomnia sufferers who meet criteria for a comorbid sleep disorder in addition to  insomnia disorder will also be excluded

The focus of this study is to test the efficacy of a 12-week, phone-delivered Positive  Psychology-Motivational Interviewing (PP-MI) intervention, with additional twice weekly PP  and health behavior text messages for a total of 24 weeks (with interactive,  algorithm-driven, goal-focused text messages in the final 12 weeks), compared to an  attention-matched MI-based educational condition, in a randomized trial (NIH Stage II) of 280  patients with New York Heart Association class I-III Heart Failure (HF). The investigators are proposing a study that will focus on testing the efficacy of a Positive  Psychology-Motivational Interviewing (PP-MI) intervention, with additional twice weekly PP  and health behavior text messages for a total of 24 weeks (with interactive,  algorithm-driven, goal-focused text messages in the final 12 weeks) in patients with New York  Heart Association class I-III HF. The investigators will enroll 280 HF patients, who will  take part in a 12-week (with 24 weeks of supplemental text messages) health behavior  intervention.  In this project, the investigators hope to do the following:  1. Examine the efficacy of a 12-week, phone-delivered PP-MI intervention for individuals  with heart failure (HF) on health behavior adherence at 12 weeks (primary time point),  24 weeks, and 48 weeks.  2. Assess the intervention's impact on psychological outcomes, health-related quality of  life (HRQoL), HF-specific quality of life, HF symptoms, and function.  3. Explore the intervention's impact on markers of cardiovascular health (e.g., blood  pressure), as well as major adverse cardiac events, HF hospitalizations, and mortality.  Participants will undergo two visits during which they will meet with study staff. During the  first visit, participants will provide informed consent, answer questionnaires related to  psychological and physical health and functioning, have their blood pressure and weight  measured, and be asked to monitor their physical activity (using an accelerometer) for one  week and medication adherence (using an electronic pill bottle) for two weeks. Participants  will be given a urine collection container and asked to provide a urine sample within 4 hours  of their first void and before eating breakfast on the day of Visit 2. At the second  in-person visit, the urine sample will be collected, and upon confirmation of adequate  physical activity and medication adherence data, participants will be randomized to receive  the PP-MI intervention or the MI-alone intervention.  Following randomization, all participants will be provided a treatment manual corresponding  with their treatment condition, a Fitbit activity tracker, and other treatment materials. The  appropriate intervention will be introduced, and the first exercise will be assigned.  Following the second in-person visit, participants in both treatment conditions will complete  twelve weekly phone sessions with a study trainer. The phone sessions primarily will include  a review of the prior week's session content and a discussion of the rationale and assignment  of the next week's exercise/assignment.  Participants in both treatment conditions will receive twice weekly text messages throughout  the intervention (Weeks 1-12) and initial follow-up period (Weeks 13-24). During the  intervention, these messages will provide information about the PP activity (PP-MI group) and  health behavior goal (both groups) discussed that week. During Weeks 13-24, participants in  the PP-MI condition will engage with twice weekly, automated, interactive text messages  related to PP and health behavior goals. Individuals in the MI-alone group will receive  identical messages related to setting health behavior goals as the PP-MI participants and  will additionally receive a fixed test message providing education about health behavior  adherence.  At Weeks 12, 24, and 48, participants will complete follow-up visits. One week prior to these  visits, participants will be mailed an accelerometer and will wear it until their study  visit. They will also be sent a container for urine collection, which they will bring to  their follow-up visit. During these study visits, participants will be asked to answer  questionnaires related to psychological and physical health and functioning, have their blood  pressure, weight, and waist circumference measured, will perform a 6 minute walk test, and be  asked about cardiovascular outcomes, including hospitalizations, cardiovascular procedures,  and cardiac-specific hospitalizations.  Finally, participants will complete phone sessions every 6 months until study end to inquire  about hospitalizations and adverse cardiac events. Inclusion Criteria:  -  Adult patients with NYHA class I, II, or III HF.  -  Suboptimal adherence to health behaviors. This will be defined as a total score of ≤15  on three Medical Outcomes Study Specific Adherence Scale (MOS) items regarding  diet/exercise/medications. Exclusion Criteria:  -  Cognitive deficits impeding a participant's ability to provide informed consent or  participate, assessed via a 6-item cognitive test.  -  Medical conditions likely to lead to death within 6 months.  -  Inability to participate in physical activity due to another medical condition (e.g.,  arthritis).  -  Inability to read, write, or speak in English.  -  Current participation in another intervention or program that has been designed to  promote well-being or health behavior adherence.

Based on the basic data of all patients foreseen for a local hyperthermia in the  participating centers the failure rate (of the Celsius TCS Hyperthermia System) and the  complication rate (injury to the patients) will be recorded. During this PMCF Trial from each participating center the internal data of all Celsius TCS  Hyperthermia devices are collected. The participating centers are obligated to report any  device-related failure and Adverse Event (injury to the patient). The center reports together  with the device-internal data allows to calculate the failure and the complication rates. It  will be analyzed regarding the kind of tumor and the concomitant treatment (radiotherapy  and/or chemotherapy). The outcome groups (with/without failure or complication) will be  analyzed regarding demographic and treatment parameters. Inclusion Criteria:   -  treatment performed with the Celsius TCS Hyperthermia System Exclusion Criteria:   -  not applicable -

Cancer patients could experience physical limitations, cognitive symptoms, fatigue and pain,  that could be perceived at diagnosis but may also occur during treatment, limiting the person  from carrying out their activities of daily living, including work tasks. Return to work is a  major goal, as it facilitates the patient's ability to deal with the disease and improve  general health.  At present, there is no path aimed at supporting cancer patients in the return to work  process. Because of this, the investigators want to assess the feasibility of a  multidisciplinary social-health care pathway aimed at manage the difficulties that cancer  patients might perceive in the return to work process. To receive the support from the social-health care pathway, cancer survivors should go to an  information desk service (called Informa Salute) located in the hospital. Here,  sociodemographic and work-related data will be collected with the aim to organize the  tailored social-health support to facilitate the return to work.  The social-health care pathway created includes: the local Health Authority of Reggio Emilia  and the local Order of Physicians, voluntary non-profit associations, vocational and  educational training bodies, social cooperatives, one labor union and one chartered  accountant enterprise. Inclusion Criteria:   -  adults with cancer diagnosis and employed at the time of diagnosis Exclusion Criteria: -

This study aims to compare the effectiveness of Dextenza vs standard of care prednisolone  taper after cataract surgery in diabetic patients with regards to controlling post-op  inflammation at post-op days 7, 14, and 30. The inflammation after cataract surgery is controlled at the investigators' institution by a  taper of prednisolone acetate 1%, which consists of four drops daily for one week, followed  by three drops daily for one week, then two drops daily for one week, then one drop daily for  one week. Due to the frequency of drops needed after cataract surgery, compliance with the  post-op regimen often wavers. This study aims to evaluate the efficacy of Dextenza, which has  been shown to be better than placebo after cataract surgery (1), against prednisolone acetate  taper. If shown to be as effective without compromising safety, it could be a very convenient  alternative to prednisolone acetate taper. Furthermore, if Dextenza is shown to be as  effective as prednisolone taper in diabetic patients, it could be logically generalized that  it would be effective in patients without diabetes as well, as patients without diabetes (and  with no confounding risk factors, such as a history of uveitis) are less prone to developing  post-op macular edema. Risks are minimal for this FDA approved treatment and include  iridocyclitis (10%); intraocular pressure increased (6%); visual acuity reduced (2%); cystoid  macular edema (1%); corneal edema (1%); eye pain (1%) and conjunctival hyperemia (1%). These  risks are comparable to prednisolone acetate. Inclusion Criteria:  -  Patients with diagnosed diabetes  -  Patients must be undergoing cataract surgery in each eye  -  Patients must have no worse than moderate nonproliferative diabetic retinopathy Exclusion Criteria:  -  Patients must not have any history of documented macular edema on OCT  -  Patients must not have any macular edema on pre-op OCT  -  Patients must not have any history of uveitis  -  Patients must not have severe nonproliferative or proliferative diabetic retinopathy  -  Patients with operative complications will be excluded from this study  -  Patients with any active corneal disease, infectious or rheumatologic, will be  excluded  -  Patients must not be pregnant

Cheeks appearance is a screening tool developed based on cheeks observation to identify  volume, flaccidity or both to predict people with probable obstructive sleep apnea. Cheeks Appearance for Sleep Apnea (CASA score) is a screening tool developed to observe  adults people cheeks appearance to identify volume, being 0 for no volume, 1 for mild volume,  2 for moderate volume and 3 for severe volume; or flaccidity, being 0 for no flaccidity, 1  for mild flaccidity, 2 for moderate flaccidity and 3 for severe flaccidity. In the end of  CASA score screening we sum up the score of volume with the score and the flaccidity score to  reach the CASA score, the final result that can range from 0 to 6 points.  This study was applied in three moments, being the first one only the application of CASA  score and a facial imaging to facilitate the replicability. The data collection and  enrollment of 248 participants were made in a sleep private clinic in participants undergoing  polysomnography. All this part of data collection was applied for a 3 months period. This  first part was the validation of CASA score protocol with internal validity.  The second part was carried out 1 year after in which all participants enrolled were  evaluated by CASA score and facial imaging, as the first part, in a sleep private clinic  while doing polysomnography. Additionally, procedures such as ultrasonography images of  specific orofacial muscles, followed by tongue and cheeks pressure evaluation were carried  out just after the CASA score and facial imaging based on photography registers. In this  second part, others 71 participants were recruited.  The third and last part was a case-control study in which 20 of the 71 anterior part of the  data collection were invited to take part in the last part of the study, that was the  fiberoptic endoscopic evaluation of swallowing, so 10 non obstructive sleep apnea  participants and 10 obstructive sleep apnea participants were chosen and invited, 19 accepted  and carried out the last part. This last part was underwent in an outpatient clinic of an  otorhinolaryngologist or ear, nose and throat physician (ENT) with a Speech and Language  Therapist (SLT).  Description of the methods:  Ultrasonography was made with a portable device which was positioned in the face of the  participant and slide for the direction needed to capture the image of the muscle targeted  like masseter, buccinator and tongue. Those were the three muscles evaluated by the  ultrasonography exam.  Tongue and cheeks pressure evaluation was made with IOPI medical equipment which had a small  bulb coupled in the device and its bulb was positioned inside the mouth of the participant in  the tongue and the participant was instructed to press as hard as he could against the hard  palate. In the cheeks was positioned in the oral vestibule between the cheek and the teeth,  and the pressure was applied by the cheeks.  Fiberoptic endoscopic evaluation of swallowing (FEES): a micro camera of a endoscopy was  inserted in the participant nose to look the nasopharynx and oropharynx. The fiberoptic was  kept in the nasopharynx to see the participant eating, first a liquid consistency (5 and 10  ML), pureed consistency (5 and 10 ML) and solid food (half cracker and 1 whole cracker). The  whole exam lasted 15 to 20 minutes, maximum. Inclusion Criteria:  -  Sleep complaints  -  18 years old or older  -  Undergoing polysomnography in the private sleep clinic Exclusion Criteria:  -  Previous OSA diagnose  -  Severe comorbidities such as neurologic diseases or others condition that could cause  facial edema or facial deformities  -  Facial hair that could difficult the facial landmarks visualization  -  Previous facial surgical procedure

This study is a phase III which includes two treatment phases. The phase 1 study is a  multi-center, randomized, double-blind, placebo- controlled, parallel group that provide  primary efficacy and safety data.  The Phase 2 study is a single-arm, open-label conducted in a subset of subjects who completed  the phase 1 study to provid additional long-term safety and efficacy. The phase 1 study which includes the screening phase (up to 3 weeks) and treatment phase (12  weeks). After signing the informed consent, the inclusion and exclusion criteria will be  confirmed preliminarily at screening visit and reconfirmed at Day 1 (baseline). At least 418  eligible subjects will be randomized in a 1:1 ratio to receive 6.5mg of intravaginal  prasterone or placebo once-daily for 12 weeks.  The phase 2 study which includes the treatment phase (26 weeks). A total of 100 subjects who  have completed Phase 1, not occur adverse event（AE） grade ≥3 or serious adverse event (SAE),  or recover all AE grades ≤1, and voluntary to participate in Phase 2 study. After signing the  ICF, the subject will receive 6.5mg of intravaginal for 26 weeks. Inclusion Criteria:  1. Subject is between 40 and 80 years of age inclusive;  2. Menopausal women (with or without hysterectomy) must also meet 1 of the following 3  conditions:  A Non-hysterectomy, menopause ≥ 12 months; B. Menopause > 6 months and < 12 months or  premenopausal hysterectomy, follicle stimulating hormone (FSH) > 40 IU/L; C ≥ 6 months  since baseline assessment (Day 1) with or without hysterectomy.  3. At screening and baseline (Day 1), the subject presented with moderate-severe  dyspareunia (dyspareunia) as measured by the Vaginal Atrophy Symptom Questionnaire  (VASQ) and self-rated as the most bothersome symptom.  4. ≤ 5% superficial cells by vaginal smear at screening and baseline (Day 1).  5. Vaginal pH > 5 at Screening and Baseline (Day 1).  6. Women (with or without a partner) who currently have sex or other sexual activity  (masturbation, etc.) at least once a month, or who have sex or other sexual activity  at least once a month in the past, with reduced sexual activity due to excessive pain  or vaginal dryness.  7. Normal physical examination of the breast and normal mammographic findings (BI-RADS  grade 1 or 2) within 9 months prior to the baseline visit (Day 1).  8. Normal cervical smear results (including inflammatory changes), regardless of  hysterectomy (no abnormal cervical smear in the past 2 years if ASCUS is present, and  human papillomavirus (HPV) test negative can be used) within 12 months before the  baseline visit (Day 1).  9. Voluntarily participate in this clinical trial and sign the informed consent form  (ICF).  - Exclusion Criteria:  1. Patients with a history of malignant tumor.  2. Have active or history of thromboembolic disease (excluding thromboembolic events due  to accidents, surgery, immobilization).  3. Clinically significant endocrine metabolic disease (e.g., diabetes mellitus) not  controlled with medication.  4. Use of estrogen injections, estrogen implant sticks, progestogen injections,  progestogen implants, androgens, anabolic steroids within 6 months of the screening  visit.  5. Use oral estrogen, oral progesterone, prasterone (DHEA) or intrauterine progesterone  treatment, intravaginal hormonal drugs (ring, cream, gel or tablet), estrogen alone or  estrogen/pregnancy within 8 weeks before the screening visit, hormone transdermal drug  users.  6. Confirmed depression with poor control under standard treatment or history of  diagnosed psychiatric disorder.  7. Those who have participated in or plan to participate in other drug or device clinical  trials during the study period within 1 month prior to the screening visit.  8. Laboratory findings suggestive of glutamic-pyruvic transaminase (ALT), glutamic  oxaloacetic transaminase (AST) ≥ 2 times the upper limit of normal, or creatinine ≥  1.5 times the upper limit of normal.  9. Grade 2 and higher uterine prolapse (cervix reaching labia minora).  10. Transvaginal ultrasound revealed a uterine fibroid ≥ 3 cm in diameter.  11. Endometrial thickness ≥ 4 mm by transvaginal ultrasound, or other comprehensive  assessment by the investigator with the possibility of endometrial hyperplasia,  deterioration.  12. Current endometrial polyps.  13. Previous endometrial ablation.  14. Patients with vulvar lichen sclerosus.  15. Patients with unexplained vaginal bleeding.  16. Patients who are known to be allergic to the study drug or its ingredients.  17. Patients who have participated in other relevant clinical trials of the  investigational drug (prasterone vaginal suppositories).  18. History of past or present drug or alcohol abuse (14 units of alcohol per week: 1 unit  = 285 mL of beer, or 25 mL of spirits, or 100 mL of wine).  19. Subjects who are unable to perform the procedures required by the protocol, or any  other subjects who are not suitable for this clinical study judged by the  investigator.  -

1. To compare the knee joint MRI 30 ° The flexion position was similar to that of  conventional knee joint coil (about 17 °） The advantages and disadvantages in the description  and diagnosis of anterior cruciate ligament injury;,2. To compare the knee joint MRI 30 ° The  flexion position was similar to that of conventional knee joint coil (about 17 °） Advantages  and disadvantages in description and diagnosis of patellofemoral instability Magnetic resonance imaging is widely used in the imaging diagnosis of knee joint injury. At  present, there are two kinds of scanning coils used in our country. One is flexible surface  coil, and the patient is 0 ° Scan in the straight position. The other is the special coil for  the knee joint. At this time, because the coil itself is hard material and has a certain  height, the patient is actually in the knee joint micro bending position (about 17 ° 1) Scan.  However, it may not be accurate enough to evaluate ACL injury and patellofemoral instability  with knee scan in extension and micro flexion position.,1、 Previous literatures have shown  that flexion position is superior to extension position in the description and diagnosis of  anterior cruciate ligament injury. The main reasons include: ① in extension position, the  femoral attachment is wider and flat, with the increase of flexion angle, the anterior  cruciate ligament fiber bundle is twisted, and the femoral segment is narrower in sagittal  position, Thus, it can be clearly shown as a cylindrical bundle structure 2; ② The normal ACL  was tensioned in the extension position, so the femoral attachment area was not well  displayed. With the increase of flexion angle, the femoral segment separated from the  intercondylar crest area, and the volume of intercondylar fossa increased; ③ Due to the  influence of partial volume artifacts in the extension position, the normal anterior cruciate  ligament may also show uneven MRI signal, which is similar to injury, resulting in false  positive, while the flexion position can reduce partial volume artifacts. However, there are  few studies on the advantages and disadvantages of flexion and micro flexion scanning in the  description and diagnosis of anterior cruciate ligament injury at home and abroad.,2、 The  medical research of patellofemoral instability found that in the early stage of knee flexion,  the patella of normal people began to move to the medial side of the knee while sliding from  the starting position to the distal side ° The patella moved inward gradually to the maximum,  then turned to the lateral and moved to the knee flexion of 40 ° The patella returned to the  median line 4. The patients with patellofemoral instability were 15 °- forty-five ° The  center of patella moved from the initial position to the lateral position continuously for 5,  so 30 ° The difference between normal people and patients may be more significant.,The  purpose of this study is to explore 30 cases ° Application value of flexion position in  diagnosis of anterior cruciate ligament injury and patellofemoral instability.  2.Image analysis：Comparison of the diagnosis of anterior cruciate ligament injury between  conventional scan position and 30°flexion scan  (1) Two radiologists respectively evaluated the injury of the anterior cruciate ligament.  The evaluation criteria for the full length display status are as follows: 3 points: The  anterior cruciate ligament is continuously displayed on multiple levels or the full length is  displayed in one level, without obvious artifacts; 2 points: The full length of the anterior  cruciate ligament cannot be displayed completely but the section can be displayed, there are  artifacts but it does not affect the observation; (1)point: The full length of the anterior  cruciate ligament cannot be identified or artifacts affect the observation. The evaluation  criteria for the display status of the tearing point and stump are as follows: (3) points:  The tear point and stump of the ACL are clearly displayed (2) points: One of the torn points  or stumps of the ACL can be clearly displayed, and the other cannot be clearly displayed (1)  point: The tear point and stump of the ACL cannot be clearly displayed Inclusion Criteria:  injury who are planning to undergo knee arthroscopy - Exclusion Criteria:  arthritis, septic arthritis, tumor, joint fibrosis; History of knee surgery.  -

The purpose of this study is to explore the microflora characteristics of different  ecological loci and multiple metabolic pathways in Crohn's disease patients with different  disease course states. This study aims to investigate the characteristics of microflora in the oral and tongue base,  small intestinal stomy and lower respiratory tract, as well as the characteristics of  multiple metabolic pathways such as bile acid metabolism and amino acid metabolism in Crohn's  disease patients with different course states. Inclusion Criteria:  1. individuals who were clear and signed the informed consent.  2. Male and female. Exclusion Criteria:  1. Any one who can not provide accurate information.  2. Any one who denies the study.

This study will be a prospective, open-label, multi-center study that will collect safety  data for the minimally invasive PerQdisc Nucleus Replacement Device deployed to reduce  chronic low back pain. This study will be a prospective, open-label, multi-center study that will collect safety and  efficacy data for the minimally invasive PerQdisc Nucleus Replacement Device (NRD). Patients  will have degenerative disc disease (DDD) in one or more lumbar discs. The NRD is used for  surgical replacement of a single nucleus pulposus between spinal lumbar discs L1-S1 using an  anterior or lateral transpsoas approach. Currently the surgical gold standard involves spinal  fusion of the affected vertebral bodies, reducing range of motion and increasing stress on  other vertebral bodies. The goal of nucleus replacement is to reduce chronic low back pain by  maintaining disc height while preserving range of motion. Inclusion Criteria:  -  Patient is skeletally mature and between 21 and 60 years of age.  -  Patient has Degenerative Disc Disease (DDD) at one or more levels between L1 and S1  -  History and clinical findings suggestive of symptomatic DDD:  Darkened disc on MRI in T2 weighted images Patients with at least 6 months of low back pain  (location defined as the space between the lower margin of the posterior rib cage and  horizontal gluteal fold) that is resistant to nonsurgical conservative therapy.  -  Patient has adequate disc height (~6mm) at the level to be treated  -  Patient has pre-operative Oswestry Low Back Disability score of greater than or equal  to 40 (0-100 scale).  -  Patient has pre-operative back pain VAS score of greater than or equal to 40 (0-100  scale)  -  Patient has received conservative, non-surgical treatment for back pain for a minimum  of 6 months.  -  Patient has signed the approved Informed Consent Form. Exclusion Criteria:  -  Patient has had prior lumbar spine surgery  -  Spinal fusion at any level  -  Patient has ankylosing spondylitis or other spondyloarthropathy.  -  Patient has isthmic spondylolisthesis or degenerative spondylolisthesis greater than 2  mm.  -  Patient has congenital moderate or severe spinal stenosis or epidural lipomatosis.  -  Patient has significant facet disease.  -  Patient has had prior lumbar spine surgery  -  Spinal fusion at any level  -  Patient has any known active malignancy.  -  Patient has previously undergone or currently on immunosuppressive therapy. Steroids  used to treat inflammation are allowed.  -  Patient has active local or systemic infection.  -  Patient has been diagnosed with hepatitis, rheumatoid arthritis, lupus erythematosus,  or other autoimmune disease, including AIDS, ARC and HIV.  -  Patient has diabetes mellitus (Type 1 or 2), requiring daily insulin management.  -  Patient is pregnant or plans to become pregnant during the course of the study.  Pregnancy ruled out by urine or serum HCG.  -  Patient has a known allergy to silicone (polymer and balloon material) or barium  sulfate (polymer).  -  Patient participated in another investigational drug or device study within the past  30 days.  -  Patient belongs to a vulnerable population or has a condition such that his/her  ability to provide informed consent, comply with follow-up requirements, or provide  self- assessments is compromised (e.g. developmentally disabled, prisoner, chronic  alcohol/ substance abuser)  -  Patient has a significant disc herniation at the level to be treated  -  Patient has a significant Schmorl's node in the level to be treated  Intraoperative exclusion criteria:  -  Protrusion of the 20A imaging balloon up to or beyond the outer margin of the vertebra  during the imaging steps.  -  Patient has a violated endplate as determined by imaging balloon during fluoroscopy  -  Patient has a disc space that is too narrow for implantation.

Hypertension (HTN) is the single most prevalent risk factor for cardiovascular disease,  diabetes, obesity and metabolic syndrome. Recent American Heart Association (AHA) statistics  indicate that one-third of all adults in the United States of America suffer from HTN.  Despite advances in life style modification and multi-drug therapies, 20-30% of all  hypertensive patients remain resistant.  These individuals exhibit autonomic dysregulation due to elevated sympathetic activity and  norepinephrine spillover, and low parasympathetic activity. It is generally accepted that  this uncontrolled, resistant HTN is primarily "neurogenic" in origin, involving over activity  of the sympathetic nervous system that initiates and sustains HTN. A surgical approach such  as the recently developed "Simplicity Catheter" assisted renal denervation remains one of the  few options available to these patients. Thus, a mechanism-based breakthrough is imperative  to develop novel strategies to prevent and perhaps eventually cure neurogenic hypertension  (NH). This study is designed to evaluate a low and high dose of minocycline to test the  hypothesis that minocycline treatment would produce antihypertensive effects in  drug-resistant neurogenic hypertensive individuals. Minocycline has been selected because of  its demonstrated effects on inhibiting microglial activation and its ability to penetrate the  blood brain barrier. There is no other compound available that is safer and displays  specificity better than Minocycline in inhibiting microglial activation. Thus, the potential  therapeutic benefits of this inexpensive, well tolerated, already FDA-approved drug that has  minimal side effects would be enormous. One hundred seventy-five (175) subjects who will be randomized to receive either Minocycline  100 mg or 200 mg b.i.d. (twice a day). At baseline, subjects will undergo blood tests (lipid  panel, high sensitivity-C reactive protein, high sensitivity troponin, glucose, metabolic  profile, lipid panel, Cystatin C, albumin and flow cytometry). Peripheral blood mononuclear  cells will be isolated and used to generate human induced pluripotent stem cells (iPSCs)  which will be used for further mechanism studies.  After enrollment of the first two patients and observing a marked reduction in blood pressure  the blind was broken and patients were on active therapy. Because these patients had CVD, for  safety reasons recruitment was halted and the protocol design was modified to an open-label  design of dose titration for each participant beginning at 50 mg/day of minocycline,  escalating to 100 mg/day and 200 mg/day if the primary outcome measure of ambulatory blood  pressure monitor (ABPM) =/> to 5 mmHg decrease in mean daytime SBP was not achieved. If  patients responded, participation was completed. This revised protocol was resubmitted to the  IRB and approved on 1/6/16. An interim analysis was planned after 40 patients completed the  revised protocol.  In addition to blood collection, a physical exam will be conducted and office systolic blood  pressure (BP), diastolic blood pressure (DBP) and pulse pressure (PP) will be recorded.  Patients will be fitted with an ABPM system. Patients will wear the ABPM for 24 hours at  which point they will mail the monitor back to research personnel. At this visit, the study  drug will be dispensed and patients will be instructed to start the study medication after  completing the 24- hour ABPM monitoring period. After this visit, patients will be asked to  return every month till the end of the study at 6 months.  Monthly visits (1, 2, 3, 4, 5 and 6 month visits), will include a brief physical examination  and an assessment of medication compliance and tolerance. One tablespoon of blood will be  drawn for flow cytometry analysis, selected cytokines, markers of gut permeability including  zonulin, and iPSCs isolation at the baseline, 3 and 6 month visit only. Study drug will be  dispensed and measurement of SBP, DBP, PP and other vital signs will also be completed.  Office BP readings will be taken in a seated position after 5 minutes of rest according to  Joint National Committee VII Guidelines. At baseline, BP will be measured at each arm, and  the arm with the higher BP will be used for all subsequent readings. Averages of the  triplicate measures will be calculated and used for analysis. At baseline and each followup  visit, patients will be asked to wear the ABPM for 24 hours. Subjects will mail the cuff back  to research personnel when completed. ABPM will be performed using an oscillometric Spacelabs  90207 monitor (Spacelabs Healthcare, Issaqua, WA) with readings taken every 30 minutes in  daytime and every 60 minutes at nighttime. ABPM readings will be averaged for, daytime and  nighttime. Patients will be assessed while adhering to their usual diurnal activity and  nocturnal sleep routine. The antihypertensive drugs, and their doses, used at each visit will  be recorded on standardized forms along with any reports of adverse experiences known to  occur with the drugs used (e.g. lightheadedness, dizziness, syncope, etc.).  If patients respond to treatment, by protocol defined drop in daytime ABPM and/or the need  for down titration of hypertensive therapy they will be considered a responder, complete the  final visit and complete study participation. At the final visit, the same blood tests at  baseline will be repeated. When the patients complete the 6 months of treatment or are  considered a responder at a lower dose, they will come in for their final visit, and return  the ABPM monitor, their participation in the trial will be considered as complete.  A subset of responders and nonresponders were sent to Montreal as part of IRB201500594 -N to  carry out novel brain imaging of sympathetic centers, and perform autonomic testing. Inclusion Criteria: None Exclusion Criteria: None

Little evidence exists on the impact of diabetes risk scores, e.g. on physicians and  patient's behavior, perceived risk of persons, shared-decision making and particularly on  patient´s health. The aim of this study is to investigate the impact of a non-invasive  diabetes risk prediction model in the primary health care setting as component of routine  health checks on change in physical activity. Diabetes risk scores are predictive models to estimate the probability for an individual to  develop diabetes within a defined time period. In the last years, many diabetes risk  prediction models were developed worldwide. It has been proposed that using diabetes risk  scores as first step of diabetes screening is more practical than blood glucose tests as the  latter are time consuming and costly. Given the rapid development of diabetes risk scores and  a simultaneous reluctance of primary care physicians (PCPs) to implement diabetes risk scores  in everyday practice, there is an urgent need to expand our knowledge of the impact of  diabetes risk scores in the primary health care setting. Thus, the aim of the study is to  investigate the impact of a non-invasive risk prediction model in the primary health care  setting as component of routine health checks on change in physical activity. Inclusion Criteria:  -  general practitioners, medical practitioners and internists working as general  practitioners with and without further training in diabetology according to German  Diabetes Association standards  -  provide the routine health check  -  appointment for the routine health check  -  insured in statutory health insurance  -  age > 35 years  -  Body Mass Index (BMI) of ≥ 27 kg/m2 Exclusion Criteria:  -  treat exclusively patients with private insurance  -  treat exclusively diabetes patients in a specialized medical practice  -  type 1 or type 2 diabetes diagnosis or already abnormal blood glucose level (fasting  glucose ≥ 126 mg/dl or 2 hours oral glucose tolerance test (oGTT) ≥ 200mg/dl or  glycated hemoglobin (HbA1c) ≥6,5%) before the routine health check  -  no sufficient German language skills to fill in the questionnaires  -  presence of an incurable disease with a prognosis of less than one year  -  severe mental illness or dementia  -  severe underlying disease, which largely impairs physical activity  -  pregnancy  -  participation in another clinical study 30 days before study inclusion

This study evaluates the addition of intranasal oxytocin to the treatment of Major Depression  using interpersonal psychotherapy. Half of the participants will receive a placebo adjunct to  interpersonal psychotherapy, and the other half will receive oxytocin. Depression is a debilitating mental health condition that carries great consequences for both  the individual and society. Crucially, at least one third of depressed patients do not  respond to existing interventions and relapse rates are high, alerting scientists to the need  to explore possible adjunctive treatments and novel therapeutic targets. In this regard,  research on the use of oxytocin in the treatment of depression is promising.  It is well documented that interpersonal stress predicts the onset of depression, and that  social isolation is a symptom of psychological distress that can leave patients with a poor  prognosis for recovery. Therapeutic interventions focused on the alleviation of social  conflict and strengthening of social bonds (i.e. Interpersonal Psychotherapy; IPT) show  greater efficacy for the treatment of depression than other psychological interventions (NIMH  Treatment of Depression Collaborative Research Program; Elkin et al. 1984). It has been  posited that oxytocin, a naturally produced hormone that is involved in social-support  seeking and stress-regulation, could represent a biological link between social stress and  depression in adulthood. The salubrious effect of exogenous oxytocin on human social behavior  is well documented: Oxytocin has been shown to make individuals feel more securely attached  in their social relationships, increase their trust in others and openness to new ideas,  improve their recall of specific and positive social autobiographical memories, and improve  social learning. Importantly, these factors have been shown to improve the efficacy of  Interpersonal Psychotherapy. Thus, It stands to reason that the use of oxytocin as an adjunct  to IPT could improve its efficacy for the treatment of depression, which is an important  prospect when considering that a third of patients do not respond to existing therapies.  In the proposed research project, we will conduct a Randomized Controlled Trial for the  treatment of Major Depression with IPT and adjunctive oxytocin. Patients will be screened for  eligibility, undergo structured psychotherapy for twelve weeks, and will be followed  longitudinally for changes in quality of social functioning, interpersonal stress,  psychiatric symptoms and depressive relapse. Establishing novel interventions for depression  could position healthcare providers to better alleviate the burden and personal suffering  caused by this disorder. Inclusion Criteria: • Current Major Depressive Episode Exclusion Criteria:  -  Visual impairment  -  Major medical illness [A condition that is chronic and associated with impaired  functioning, distress, or frequent medical intervention), in particular, subjects with  evidence or history of malignancy or any significant hematological, endocrine,  cardiovascular (including any rhythm disorder), respiratory, renal, hepatic, or  gastrointestinal disease  -  Acute or chronic nasal diseases or obstruction  -  Current (in the last month) use of any endocrine-relevant or psychotropic medication  other than prescription antidepressants  -  Current substance dependence or abuse  -  Use of illicit drugs (stimulants, narcotics, psychedelics/hallucinogens,  non-prescription medication) in the past 8 weeks  -  Lifetime history of a psychosis (except if part of MDD) or pervasive developmental  disorder  -  Past or current comorbid axis-1 disorder except Dysthymia, Adjustment Disorder,  Generalized Anxiety Disorder, Social Phobia, and Specific Phobia.  -  Female Only: Females of child bearing potential cannot be pregnant or breastfeeding in  order to participate in this study. They must not be planning to become pregnant, and  must be willing to use appropriate contraception throughout the study.  -  Female Only: To control for hormonal changes related to pregnancy, females will also  be excluded if they have previously given birth.

Since the beginning of the pandemic, several authors (Lee, 2020; Sahu, 2020; Zhai & Du, 2020)  have highlighted the various challenges faced by university students, as well as their  negative effects on their mental health. A deterioration in their mental health was observed,  particularly during lockdown, with very high levels of anxiety and depressive symptoms  (Essadek & Rabeyron, 2020; Husky et al., 2020; Le Vigouroux et al., 2021; Odriozola-González  et al., 2020). In addition, COVID-19 has brought about a digital revolution in higher  education (Strielkowski, 2020). However, distance learning was not without consequences on  student stress (IAU, 2020). The detrimental effects of distance education, in terms of stress  and anxiety, could also have important consequences for students' learning and academic  success.  Our research proposes to evaluate effects of an intervention focused on stress and learning  on mental health and learning strategies. This intervention will be proposed to students from  University of Nimes. Its primary objective is to prevent psychological health alterations and  to improve students' learning strategies.  Three groups will be constituted: a group that will participate in an online program (online  group), a group will participate in a hybrid program, i.e. with online content and  face-to-face support (hybrid group) and a group that will not be receiving any interventions  (control group). The investigators plan to include between 150 and 200 university students,  between 40 and 70 in each group.  The levels of mental health and learning strategies of the two experimental group (online and  hybrid group) will be compared to a control group with the realization of pre and post  intervention measures. Sociodemographic (e.g., level education) and situational variables  (e.g., diagnostic of COVID-19) will be considered in the analyses. In March 2020, the World Health Organization declared the coronavirus disease 2019 (COVID-19)  as a global pandemic. In France, all universities have been closed on 16th March 2020. In  September 2020, face-to-face teaching restarted in French universities, but with new  constraints (e.g., reducing number of students in classrooms, wearing masks) and significant  changes in teachings (e.g., distance and/or hybrid education). In October 2020, several  French universities closed down again due to significant contamination among students.  Finally, on 30th October 2020, the French government imposed a second lockdown and all  universities have been closed. It is only in February 2021 that face-to-face teaching started  again in French universities (within the limit of 50% of the universities' capacity and 20%  of the teachings).  Since the beginning of the COVID-19, a deterioration in their mental health was observed,  particularly during lockdown, with very high levels of anxiety and depressive symptoms  (Essadek & Rabeyron, 2020; Husky et al., 2020; Le Vigouroux et al., 2021; Odriozola-González  et al., 2020). This may be explained in part by the fact that people who were experiencing  high levels of psychological distress prior to the pandemic are the most vulnerable (Druss,  2020; Yao et al., 2020), and before COVID-19, university students were already identified as  a vulnerable population (see literature review: Paula et al., 2020). Before COVID-19, a  central element of students' psychological distress was their difficulties coping with an  accumulation of hassles, such as university pressure, schedule changes or financial  difficulties (Réveillère et al., 2001). The pandemic confronts students with new and  unprecedented events (e.g., online learning, online examinations, regular and significant  changes to their schedule) that challenge their ability to adapt (Araújo et al., 2020; Zhai &  Du, 2020). Recent research has shown that the more university students used avoidance  strategies during lockdown, the more they had symptoms of anxiety and depression (Dawson &  Golijani-Moghaddam, 2020; Le Vigouroux et al., 2021). In addition, the inability to tolerate  uncertainty in the COVID-19 pandemic can trigger fear of virus (Schimmenti et al., 2020) and  impact negatively on psychological well-being (Satici et al., 2020).  COVID-19 has brought about a digital revolution in higher education (Strielkowski, 2020).  However, distance learning was not without consequences on student stress (IAU, 2020). This  confronts students with new obstacles (e.g., technological, personal, family; Baticulon et  al., 2020). The detrimental effects of distance education, in terms of stress and anxiety,  could also have important consequences for students' learning and academic success. Indeed,  the more depressive and anxiety symptoms learners have, the more their academic difficulties  are exacerbated (Mills & Blankstein, 2000), and the less successful their learning strategies  are (Warr & Downing, 2000). Furthermore, the fear of losing an academic year was the concern  that most exacerbated students' lockdown anxiety (Hasan & Bao, 2020).  The deleterious effects of the pandemic on students' health are now evident. However, some  areas of research are still under-explored.  1. Most of the research is largely descriptive and do not identify the factors involved in  the deterioration in mental health and learning  2. To date, no interventional studies have been conducted to prevent these deteriorations  during the pandemic.  To fill these gaps, our research proposes to evaluate the effects on mental health and  learning of a program focused on stress and learning. Our program has been pre-tested during  the 2019-2020 academic year. It included nine modules (that take place over 9 weeks) composed  of video capsules, with the following themes: stress information, learning information,  emotion and stress regulation strategies, cognitive and metacognitive learning strategies,  motivation for learning, physical activity, diet, sleep, and managing worry and uncertainty.  Particular attention will be paid to the communication tools in order to provide graphic  coherence, facilitating the understanding and appropriation of the different media. Our  program is based on modules from previous online student mental health intervention studies.  It presents, however, two innovative aspects: 1) elements and examples specific to the  COVID-19 pandemic and 2) the addition of modules focused on learning strategies. It is  therefore an original program, designed within the framework of this research, and adapted to  the context of the COVID-19 pandemic (notably concerning the themes of concern, the  stressors, or the distance learning courses). The different modules were designed by five  associate professors: two specialized in cognitive psychology, experts in learning, two  specialized in clinical psychology and cognitive and behavioral therapy, experts in stress  and emotion regulation, and one specialized in health psychology, expert in acceptance and  commitment therapy. Two Master students in clinical psychology and two undergraduate students  in psychology were involved in the process. All the modules are the result of a collaborative  effort between the associate professors who contributed their expertise and the students who  pre-tested the modules and help improve their design to make them attractive to other  students.  For the control group, the videos will be posted every week on a You Tube channel and  broadcast on a private discord group. After each video, an associate professor will invite  the students to share their feelings, comments, or questions, about the videos in this group.  In addition, this researcher will moderate the exchanges. For the hybrid group, student will  have to attend 10 lessons of 2 hours. These courses include the viewing of videos and a time  for discussion between students and the teacher.  Participants were repeatedly reminded that the program was not a substitute for medical  and/or psychotherapeutic care. They were also informed of the services offered by the  university (in particular, preventive medicine and health promotion services) which could  accompany should they need it. Each participant was identified by a code to aggregate the  data between the different measurement times and preserve anonymity. The recruitment was  based on voluntary participation and no compensation was offered to participants. The latter  signed a consent form and were informed that their information will remain anonymous and  their participation was voluntary and could be withdrawn at any time. Measurements are made  before and after the intervention, using an online questionnaire (made on qualtrics secure  software). Inclusion Criteria:  -  Students at the University of Nimes (males and females) aged over 18 years old Exclusion Criteria:  -  not to be a student of the University of Nîmes  -  not signing the consent form to participate in the study  -  Participants must be in only one group. For example, being in the hybrid group is an  exclusion criterion for the online and control group.

The increased risk of transmission of COVID-19 infection causes the incidence of death in  health workers to escalate. It requires further research on risk factors and intervention in  health worker professionals, especially on immunity factors and nutritional status. Quality  of diet and nutrition is very important to support the immune system when infected. Several  probiotic strains have been shown to decrease the duration and incidence of diarrhea and  respiratory infections, suggesting the Gut-Lung Axis pathway. Some probiotics also improve  the balance of diversity in the composition of the gut microbiota and affect body weight in  obese people. Probiotics have also been shown to improve vitamin D absorption. A combination  of vitamin D and probiotics may be an alternative to reduce gut dysbiosis that will directly  or indirectly reduce the risk and severity of viral infections including SARS-CoV-2. Obesity is increasing in Indonesia and is the cause of various diseases, especially in the  presence of Vitamin D deficiency, a state of dysbiosis, causing an increase in the  possibility of infection. Professional health workers have a high risk of COVID-19 due to  high daily exposure. Based on a review conducted by Daniel et al, it was found that 7.3% of  health workers at Reutters University tested positive for COVID-19. Based on data from the  Indonesian Doctors Association (IDI) on July 12, 2020, it was known that 61 doctors had died.  In addition, based on data from the Indonesian National Nurses Association (PPNI), 39 nurses  have died during the COVID-19 pandemic. Therefore efforts to prevent the occurrence of  COVID-19 infection by providing a combination of vitamin D and probiotics to modulate  dysbiosis that will further reduce the risk of viral infection, especially COVID-19, needs to  be investigated for its potential benefits.  Primary and secondary objectives  1. Primary Objective:  To investigate the effect of a combination of probiotics and vitamin D supplementation  in modulating intestinal dysbiosis, and vitamin D status, in people with overweight and  obesity, especially among frontline health workers.  -  To assess the mean changes in zonulin levels (as a parameter of gut integrity to  indicate the intestinal microbiota dysbiosis)  -  To assess the mean changes in serum vitamin D levels  2. Secondary Objectives:  -  To assess the relationship between nutritional status, inflammation and immunity  with the risk of COVID-19 infection in health workers.  -  To understand the difference in the mean episodes of Covid-19 infection between  treatment and placebo groups after giving probiotics and vitamin D in people with  overweight and obesity, especially among frontline health workers.  Study Design:  This study has 2 phases Phase 1: a Cross-sectional study with 160 people Phase 2: a  double-blind, randomized, placebo-controlled trial with two arms of intervention involving a  total of 80 people. Inclusion Criteria:  -  General doctors, specialist doctors, nurses and midwives who are in charge of handling  COVID-19 patients or working in COVID-19 referral hospitals for at least the last 3  months  -  20-65 years old  -  Willing to sign informed consent  -  Willing to follow the research to completion  -  BMI > 23 kg/m2 Exclusion Criteria:  -  Pregnant woman  -  Have a confirmed history of COVID-19 based on previous PCR examinations  -  Suffering from acute illness known from history and physical examination or chronic  disease (eg diabetes, SLE, cardiovascular disease) known from history  -  Currently not on a diet program for weight loss or consuming probiotics regularly in  the last 3 months as known from the anamnesis

Background:  - A number of rare inherited diseases affect only a few patients, and the genetic causes of  these conditions remain unknown. Researchers are studying the use of a new technology called  whole genome sequencing to learn which gene or genes cause these conditions. Understanding  the genes that cause these diseases is important to improve diagnosis and treatment of  affected patients.  Objectives:  -  To identify the genetic cause of disorders that are difficult to identify with existing  techniques.  -  To develop best practices for the medical and counseling challenges of whole genome  sequencing.  Eligibility:  -  Individuals who have one of the rare disorders under consideration in this study. These  conditions are generally those in which the genetic cause of the disorder is unknown.  The eligibility of most individual participants will be decided on a case-by-case basis  by the researchers.  -  Family members of affected individuals, if that family member (often a parent) may  provide genetic information.  Design:  -  Participants in this study will have at least one and in some cases several of the  following procedures:  -  A medical genetics evaluation.  -  Other tests that may include x-rays, magnetic resonance imaging (MRI) exams, and  consultations with other doctors. Not all studies are necessary for each person, but the  information from the tests may be required to proceed with some of our gene sequencing  studies.  -  Clinical photographs to document certain aspects of the disorder.  -  Blood and skin biopsy samples, or other tissue samples, as required by the study  doctors.  -  Genetic testing, as decided by the researchers. However, most participants in this study  can expect to undergo whole genome sequencing, which is a technique to study all of a  person s genes.  -  Some participants may be asked to take part in a telephone interview and/or a web-based  survey.  -  Participants will have choices about what kinds of results from whole genome sequencing  they wish to learn.  -  After the tests have been completed and the results of the genetic studies are known,  participants will be offered a return visit to the National Institutes of Health to  learn these results. During this visit, participants will be asked to complete surveys  and participate in interviews related to their decisions to participate in the study and  to learn individual genetic test results. We aim to use genome scale medical sequencing (GSMS, to include exome and whole  genome sequencing as appropriate) to discover causative molecular lesions for a set of rare,  severe phenotypes hypothesized to be caused by either somatic mutations, germline de novo  heterozygous mutations, germline inherited recessive, or germline inherited dominant  mutations in currently unknown or uncharacterized genes. The goal of this research is  threefold: to identify causative sequence variants for disorders whose molecular etiology was  previously unknown, to apply this insight to both the rare disorders under study and more  common phenotypes, and to enhance the study of mutation on a genome-wide level.  We plan to recruit approximately three to six affected individuals along with both parents  for each phenotype under study. Prospectively recruited trios will be brought to the NIH  Clinical Center for brief clinical evaluations and molecular evaluation. Each trio will be  consented to GSMS with the option to learn clinically relevant results, that is, those that  explain the disorder in question (what we refer to as the primary variant ) as well as other  clinically relevant findings discovered incidentally as part of the GSMS process (what we  refer to as secondary variants ). Participants will be offered a return visit to NIH to learn  these results.  Sequence data generated at the NIH Intramural Sequencing Center (NISC) will be screened by  staff in the Biesecker laboratory for sequence variants that conform to the hypothesized  inheritance pattern. All sequence variants deemed clinically relevant will be validated in a  CLIA-certified laboratory and the results returned to that participant. This protocol is  being designed in a way that will provide the long-term potential for pursuing many different  clinical projects. Inclusion Criteria:  An individual who is affected with a disorder under study and is older than 4 weeks. Our  initial list of exemplar disorders has been discontinued; these disorders were examples of  those which meet the general attributes for inclusion in this protocol. As stated above,  individuals with disorders we choose to investigate under this protocol will generally  represent simplex cases with rare phenotypes whose molecular etiology is unknown.  In rare instances, we may accept DNA from deceased individuals, including DNA or other  saved biological specimens from deceased fetuses/neonates in accordance with Policy 400.  These samples may provide us exceptional opportunities to study variants and manifestations  of severe genetic overgrowth disorders where the fetus/neonate is unviable due to the  severity of manifestations. In the rare circumstance where we plan to accept samples from  non-viable fetuses/neonates, we may engage with pregnant mothers to begin consent  discussions and coordinate specimen collection. We will only enroll pregnant women who  voluntarily donate fetal tissue from invasive prenatal testing, and for which trio analysis  is appropriate and necessary. While rare, there may be circumstances in which the  scientific objectives (to elucidate the molecular etiology of the proband s genetic  condition) would not be possible without analyzing the DNA of the fetus/proband and the  biological parents. The conditions set under 45CFR46.205 are met for the inclusion of  non-viable neonates:  -  Vital functions of the neonate will not be artificially maintained;  -  The research will not terminate the heartbeat or respiration of the neonate;  -  There will be no added risk to the neonate resulting from the research;  -  The purpose of the research is the development of important biomedical knowledge that  cannot be obtained by any other means; and  -  The legally effective informed consent is obtained in accord with applicable  regulations.  Family members of an affected individual where that family member (often a parent) is  potentially informative or useful for linkage or other bioinformatic analyses of genetic  variants may be enrolled. Probands who are minors or decisionally impaired adults are  eligible if they have a parent or legal guardian who has authority to sign a consent form  on their behalf.  EXCLUSION INCLUSION:  Probands who are adults and decisionally impaired are ineligible if they do not have a  legal guardian who has authority to sign a consent form on their behalf.  Subjects who have known, significant affective or psychiatric disorders that, in the  judgment of the team, may impair their ability to understand and appropriately use complex  medical and genetic information will be considered decisionally-impaired and will be  ineligible unless they have appointed (or, in the case of minor children, are in the  custody of) an appropriate surrogate decision-maker.  In addition, guardianship for cognitively impaired adult probands must be legally  established and proof of guardianship must be supplied prior to that family s enrollment.  We request the ability to use this protocol for multiple genetic disorders, without  specifically delineating them a priori. We believe this approach to be appropriate because  for nearly all inherited disorders, the risks and benefits of GSMS do not substantively  differ. This concept was validated by our now-closed protocol 94-HG-0193, which was a  broad-based protocol for heritable congenital anomaly disorders, many of which do not fall  neatly into a specific diagnostic classification.  As mentioned, we may request permission to retain some information about prospective  participants who, at the time of their inquiry, may not be eligible for the study but who  could become eligible in the future. As these participants will not be signing a consent  form, we propose to NOT count these participants in our Inclusion Enrollment Reports but  will provide the IRB with a tally of retained records at each Continuing Review.  Consent documents for this protocol are available in English and Spanish. In rare  instances, we may enroll participants who speak other languages using the NIH Short Written  Consent Form Translation.  We will not enroll pregnant women, except as outlined in the section above. Exclusion Criteria: None

Patients with heart failure (HF) need multiple guideline-directed medications to control the  systolic and/or diastolic ventricular dysfunction. Laboratory measure the biomarker NT-proBNP  (N-terminal pro-B type natriuretic peptide) to support clinical decision and to guide  treatment at every stage of HF. Many patients (including HF patients) do not follow  therapeutic recommendations. Electronic monitoring of medication intake gives precise  information over time and is the gold standard to unveil inappropriate behaviour. Electronic  Health Records (EHR) are repository of patient health data in digital format and are mostly  locally configured in medical practices.  We aim to transmit laboratory results of NT-proBNP and estimates of medication adherence into  the EHR system of primary care providers, with the objective to guide treatment and dose  adjustment of multiple medications in patients with HF. Our project is *not* to develop a  telemonitoring system. Patients with heart failure (HF) need multiple guideline-directed medications to control the  systolic and/or diastolic ventricular dysfunction. To support clinical decision and to guide  treatment at every stage of HF, the measurement of the biomarker NT-proBNP (N-terminal pro-B  type natriuretic peptide) has been recommended.  Many patients (including HF patients) do not follow therapeutic recommendations.  Non-adherence to treatment can lead to acute decompensation that often requires urgent  hospitalisation. Electronic monitoring of medication intake gives precise information over  time and is the gold standard to unveil inappropriate behaviour. We developed Time4MedTM, a  small device that records date and time of medication intake. The recorded electronic data  are visualized in a scatter diagram and several adherence estimates can be calculated such as  days with missed doses, taking adherence or timing adherence. Electronic Health Records (EHR)  are repository of patient health data in digital format and are mostly locally configured in  medical practices.  We aim to transmit laboratory results of NT-proBNP and estimates of medication adherence into  the EHR system of primary care providers, with the objective to guide treatment and dose  adjustment of multiple medications in patients with HF. Our project is *not* to develop a  telemonitoring system.  This is a prospective, observational, feasibility study one medical practice in Basel-Stadt,  one dedicated laboratory, and one community pharmacy as study centre.  Physicians will order NT-proBNP measurement and electronic adherence monitoring to patients  with diagnosis New York Heart Association (NYHA) stage II-III, who are under  guidelines-recommended multiple medications and whose clinical and/or biomedical targeted  values are unmet (inadequate control). Laboratory and adherence reports will be generated in  similar encrypted format and transferred via secured platform into physician's EHR.  We expect to show that electronic adherence reports can be gathered and electronically  transferred by pharmacists into medical EHR in the same way as laboratory reports. The joint  availability of medication adherence estimates and laboratory values in the EHR can guide  physicians in the management and therapy of patients with HF. Inclusion Criteria:  -  is ≥ 18 years old;  -  was diagnosed with HF NYHA II-III;  -  is under multiple regimen (ACE-Inhibitors and/or mineralocorticoid receptor antagonist  (MRA) and/or betablocker (BB) and/or diuretic and/or other);  -  did not reach targeted clinical and/or biomedical objectives (HF is inadequately  controlled);  -  self-administers medication (no help or supervision from a third person);  -  is suspected of inappropriate intake behaviour;  -  accepts to use the monitoring device for one month;  -  accepts a home-visit from the study pharmacist one month later;  -  signs the informed consent form. Exclusion Criteria:  - Patients who are, in the opinion of the physician, unlikely to comply with the study  schedule or are unsuitable for any other reason

One of the most important neurological consequences following Traumatic Brain Injury (TBI) is  the development of post traumatic epilepsy (PTE). Nevertheless, there is still no effective  therapeutic intervention to reduce the occurrence of PTE. In previous studies with animals  models of epilepsy, the biperiden decreased the incidence and intensity of spontaneous  epileptic seizures besides delaying their appearance. The aim of this study is the evaluation  of biperiden as antiepileptogenic drug to prevent PTE and also the determination of side  effects, evaluating its cost-effectiveness in patients with moderate and severe TBI. One of the most important neurological consequences following Traumatic Brain Injury (TBI) is  the development of post traumatic epilepsy (PTE), which accounts for 5% of all epilepsy  etiologies in the general population. This makes TBI one of the most important causes of  secondary epilepsy, overcoming other causes such as infections, drug abuse or familiar  history of epilepsy. The occurrence of spontaneous epileptic seizures after TBI, mostly  starting in the first 2 years after moderate or severe TBI, might be as high as 86%,  specially in those with a single acute symptomatic seizure, with remission rates of 25-40%.  The causative relationship between TBI and epilepsy, as well as other types of epilepsy in  general, are still not completely understood and PTE is not yet preventable.  The therapeutic approach indicated for TBI may involve medications, surgical procedures or  both, with no effective therapeutic intervention to reduce its occurrence. Several  experimental studies in animal models have shown that drugs, which modify processes of  neuronal plasticity, have the potential to modify the natural course of PTE. Among these,  biperiden (anti-cholinergic indicated for Parkinson's disease) has shown reduction in the  incidence and intensity of spontaneous epileptic seizures and also delayed their occurence in  animal epilepsy model. Thus Biperiden would be an excellent candidate for an  antiepileptogenic agent. It is intended here to test its effectiveness and safety in adult  patients, victims of moderate and severe TBI. Patients will be randomized to receive 5 mg of  Biperiden iv, diluted in 10 ml of 0.9% saline (treatment group) or saline solution (0,9%) iv,  diluted in 10 mg of 0,9% saline (placebo group), every 6 hours for 10 days after TBI.  Prospectively, patients will be followed up for two years, on periodic visits to assess the  development of epileptic seizures. Other factors that might have benefits with the treatment,  such as epileptiform abnormalities, genetic markers and neuropsychological aspects, will also  be evaluated. The results could be important for a better compreehension of basic mechanisms  of epilepsy development. Side effects of Biperiden use, at high doses during a short period  of time, will be measured. If Biperiden is efficient and safe, it will certainly be a  low-cost option for Brazilian public health system (SUS). Inclusion Criteria:  -  Given informed consent  -  18 - 75 years of age  -  Glasgow scale higher than 6 and smaller than 12 at the trauma scene  -  moderate or severe acute traumatic brain injury  -  all genders  -  brain CT scan with signs of acute intraparenchymatous contusion Exclusion Criteria:  -  Previous use of biperiden  -  history of epilepsy (confirmed by patient chart)  -  History of seizures or use of antiepileptic medication  -  family history of epilepsy  -  pregnancy  -  participation in another clinical trial at the time of randomization  -  History of neoplasia, neurodegenerative diseases; history of stroke, cognitive  impairment, benign prostatic hyperplasia, atrioventricular block or any other cardiac  arrhythmia, or glaucoma;

Firstly, the application effect of the existing predictive models, SOAR and GWTG-Stroke, was  verified in Guangdong acute ischemic Stroke population, and the clinical application effect  of the existing predictive models was verified.  Secondly, the predictive value of clinical indicators was analyzed, SOAR and GWTG-Stroke  scores were optimized, and an improved prediction Model (New Model) was constructed.  The third is to apply the New Model to clinical practice, collect clinical data and evaluate  the prediction effect of the Model, and evaluate the prediction efficiency of the improved  prediction Model. This research is mainly divided into two parts. The first part is to verify and optimize the  existing prediction model. Through continuous collection of clinical data of acute ischemic  Stroke patients hospitalized in Shenzhen Second People's Hospital from January 2017 to  December 2021, including baseline indicators and end point events, based on the existing  prediction model (SOAR, GWTG-Stroke), The predictive probability was calculated and compared  with the actual mortality during hospitalization. The ROC curve, calibration curve and  decision curve were used to evaluate the model's differentiation, calibration and clinical  application value.  Using retrospective data, multivariate logistic regression was used to analyze the predictive  value of baseline clinical indicators, screen risk factors, and optimize the prediction model  of SOAR and GWTG-Stroke.  Extreme Gradient Boosting (XGBOOST) was used to select variables, and logistic regression  model was used based on Akaike Information Criterion.  AIC) was used to construct an improved mortality risk prediction Model (New Model). Decision  curves were used to compare the models. Combined with the clinical significance of the  indicators, the construction of the prediction Model was improved.  The model was validated internally by resampling with computer simulation. The second part is  to evaluate the clinical application effect of the improved prediction Model. The clinical  data of acute ischemic stroke patients hospitalized in Shenzhen Second People's Hospital and  Shenzhen Longhua District People's Hospital from January 2022 to December 2023 are collected  continuously. The New Model is applied in the clinic, and the New Model is validated in the  external time and space.  Evaluate prediction effectiveness and extrapolation. Inclusion Criteria:  1. ≥18 years old;  2. It meets the diagnostic criteria of China Guidelines for the Diagnosis and Treatment  of Acute Ischemic Stroke 2018, and bleeding is confirmed by head MRI or excluded by CT  after admission;  3. Admission within 72 hours of onset. - Exclusion Criteria:  1. Non-vascular causes and transient ischemic attack;  2. with severe hepatic and renal dysfunction;  3. Central nervous system infection, recent history of severe trauma, and malignant  tumors affecting survival time;  4. Incomplete main clinical data. -

There are many symptoms associated with severe asthma, not all of them related to the lung.  These are referred to as extra-pulmonary symptoms and their relationship with quality of life  is complex.  Body reprogramming (BR) is a non-drug intervention originally developed for fibromyalgia  patients with the aim of improving health and wellbeing in a personalised way, with  evidence-based lifestyle changes. The frequency and severity of multiple symptoms in severe  asthma is similar to fibromyalgia and the investigators propose that BR may be a suitable  non-drug intervention for severe asthma patients who are about to step up drug treatment.  Our study aims are therefore to assess how BR may be suitable for people with severe asthma,  and to adapt and optimise the programme for these people. In two phases, severe asthma  patients will be recruited via a regional severe asthma clinic at the Royal Devon & Exeter  NHS Trust and invited to take part in a short course of BR. In phase one, patients will be  asked to attend four weekly researcher-led sessions of BR via video call and be given  practice tasks to report on at the subsequent session. Questionnaires will be completed for  the first and last session. At the end of BR, patients will also be invited to take part in a  focus group. The data collected will inform development of the programme for phase two, which  will involve recruitment of severe asthma patient who are about to start biologic drug  treatment for their severe asthma There are many symptoms associated with severe asthma, not all of them asthma specific (e.g.  mental fog, fatigue, unexplained pain), and the relationship between these symptoms and  quality of life is complex.  Body reprogramming (BR) is another non-drug intervention originally developed for  fibromyalgia patients. BR aims to to improve health and wellbeing in a personalised way, with  evidence-based lifestyle changes. The frequency and severity of the non-asthma specific  symptoms in severe asthma are similar to those experienced by patients with fibromyalgia.  Therefore, the investigators propose that BR may be a suitable non-drug intervention for  severe asthma patients who report many non-asthma specific symptoms. This intervention  includes optimising knowledge of disease management, physical activity, relaxation and other  psychological and biological lifestyle changes which aim to improve wellbeing and mood, and  this could lead to better self-management of complex symptoms in asthma patients.  Phase 1 Eligible patients attending a severe asthma service at an RD&E Hospital will be  identified by a health professional familiar to them and invited to take part in the study by  post, including a Participant Invitation, Information Leaflet and consent form. The  Invitation Letter and Patient Information Leaflet will include instructions to read the  material carefully and to bring the consent form with them to their next scheduled clinic  appointment.  Participants will be asked to attend four weekly sessions of Body Reprogramming via group  video call using Zoom. Each session will include up to 8 patients and will consist of a 25-30  minute live presentation delivered by a researcher from the University of Plymouth. At the  end of the presentation, there will be an opportunity to ask questions or raise points of  interest. Each session will include a 'practice and report back next week' instruction, and  participants will be encouraged to provide written after completing all sessions. feedback  before Session topics will include: conceptualising severe asthma, stress and happiness,  movement and exercise, and eating and asthma triggers.  Demographics (e.g. age) and clinical data (e.g. current drug treatment) will be collected  from participants' hospital notes at the start of the programme. Participants will be asked  to complete a series of questionnaires for the first and last weeks of Body Reprogramming.  These will be posted to participants and returned to the research team using an enclosed  FREEPOST envelope. Questionnaires will include: the Severe Asthma Questionnaire (SAQ), the  General Symptom Questionnaire (GSQ), the Positive And Negative Affect Schedule (PANAS), the  Asthma Control Questionnaire. At the end of the course participants will be asked to complete  the much shorter General Symptom Questionnaire-Asthma (GSQ-A) instead of the full GSQ. In  addition to these questionnaires participants will also be asked to complete and return the  Global Rating of Change Questionnaire (GRCQ) and the Friends and Family Test after completing  the intervention. These should take no longer than 20 minutes to complete.  Following the course, participants will be invited to attend a focus group with up to 5 other  participants via video call or a one to one interview also via video. This time will be used  to discuss participants experience of Body Reprogramming, including any problems they may  have faced. This will last for up to 2 hours and will be recorded using a voice recorder for  transcription and analysis by the research team.  Analysis will include generation of summary statistics and mean differences for numerical  data, including the number of people who were invited and attended each BR course.  Thematic analysis of transcribed focus group data will be used to inform any changes which  need to made to improve the programme before Phase 2.  Phase 2 Before commencing a biologic treatment for severe asthma in normal clinic care,  patients are reviewed by a multidisciplinary team responsible for their care, and the  participating hospital's Principal Investigator will identify eligible participants.  Participant recruitment will then proceed as outlined in Phase 1.  A modified GRCQ will completed by participants at the end of the intervention in phase 2. The  changes to the wording of GRCQ are to take into account that participants have started a new  treatment (the biologic drug) and completed BR. Except for this change, the same  questionnaire data will be collected at the same time-points in this phase. Inclusion Criteria:  -  Phase one:  -  Aged ≥18 years attending the regional specialist severe asthma service in Royal  Devon and Exeter hospitals.  -  Diagnosed with severe asthma as per ERS/ATS definition.  -  Requiring high dose inhaled corticosteroids (NICE definition of high dose  ICS).  -  Eight or more non-respiratory symptoms per week (approximately 60% of patients  with severe asthma have a moderate or high extra-pulmonary symptom burden) as  measured by the General Symptom Questionnaire  -  Phase two:  -  Diagnosed with severe asthma as per ERS/ATS definition.  -  Requiring high dose inhaled corticosteroids (NICE definition of high dose  ICS).  -  Patients with severe asthma who have been approved for biologic treatment  according to national guidance and have been assessed by a multi-disciplinary  team will be offered the intervention pending starting their biologic treatment.  -  Patients with eight or more non-respiratory symptoms per week as measured by the  GSQ. Exclusion Criteria:  -  Phase one and Phase two  -  Unable or unwilling to partake.  -  In the opinion of the patient's treating physician, the patient has another  condition which is significantly impairs their ability to take part in the BR.  -  No access to the internet or appropriate IT equipment.

In patients with recurrent or metastatic renal cell carcinoma, a preliminary evaluation of  the safety and efficacy of sintilimab combined with axitinib in patients with advanced renal  cell carcinoma was conducted.Progression-free survival (PFS), overall survival (OS), disease  control rate (DCR) and disease remission rate (ORR) were evaluated. Patients with recurrent or metastatic renal cell carcinoma received axitinib tablets (5mg bid  po) combined with sintilimab (200mg d1) on a 3-week (21-day) as a one-cycle regimen.6 months  of continuous administration (i.e., 8 cycles of sintilimab) or until tumor progression or  unacceptable toxicity or death or subject withdraws informed consent;If the drug has been  discontinued or the tumor has progressed, and there are no intolerable side effects, the drug  can be continued according to the judgment of the researchers and the will of the subjects.  Drug safety was evaluated before each cycle.The first efficacy was evaluated after 2  cycles.The efficacy was then evaluated every 2 cycles. Inclusion Criteria:  -  Signed written informed consent before performance of study-specific procedures or  assessments and must be willing to comply with treatment and follow up  -  Diagnosis of locally advanced or metastatic RCC that is predominantly clear cell  histology  -  Must have measurable disease  -  Subject has received no prior systemic therapy  -  A woman is eligible to participate in the study if she is of Non-childbearing  potential, has a negative serum pregnancy test within 7 days of the first dose of  study treatment, not lactating, and agrees to use adequate contraception during the  study until at least 120 days after the last dose of investigational product  -  Eastern Cooperative Oncology Group performance status 0 or 1  -  Adequate organ function as defined in the protocol  -  Left ventricular ejection fraction >= lower limit of normal as assessed by  echocardiogram or multigated acquisition scan Exclusion Criteria:  -  Subject has an active autoimmune disease or a documented history of autoimmune disease  or syndrome that requires systemic steroids or immunosuppressive agents  -  Subject is currently participating or has participated in a study of an  investigational agent or using an investigational device within 30 days of the first  dose of study treatment  -  Subject is expected to require any other form of systemic or localized antineoplastic  therapy while on study  -  Subject is on any systemic steroid therapy, within one week before the planned date  for first dose of study treatment. Subject is on any other form of immunosuppressive  medication  -  Unable to swallow and retain orally administered medication  -  Active peptic ulcer disease, inflammatory bowel disease, ulcerative colitis, or other  -Gastrointestinal conditions with increased risk of perforation; history of abdominal  fistula, GI perforation, or intra-abdominal abscess within 4 weeks before beginning  study treatment  -  Known history of HIV infection or a known history of or is positive for Hepatitis B or  Hepatitis C  -  Presence of active infection requiring systemic therapy  -  Corrected QT interval duration prolongation  -  History of any one or more of the following cardiac conditions within the past 6  months: Cardiac angioplasty or stenting; Myocardial infarction; Unstable angina;  ----History of Class III or IV congestive heart failure according to New York Heart  Association classification  -  History of cerebrovascular accident within the past 6 months  -  Poorly controlled hypertension  -  History of untreated deep venous thrombosis  -  Presence of any non-healing wound, fracture, or ulcer, or presence of symptomatic  peripheral vascular disease  -  Evidence of bleeding diathesis or coagulopathy  -  Any serious and/or unstable pre-existing medical, psychiatric, or other conditions  that could interfere with subject's safety, obtaining informed consent or compliance  to the study procedures  -  Has taken any prohibited medications that are listed in the protocol within 14 days of  the first dose of study treatment. Subject has received or will receive a live vaccine  within 30 days before the first administration of study treatment

In this study, the effectiveness of vascular cognitive impairment was compared among the  three groups, namely, the xidezhen group, the Yangxue Qingnao pill group and the placebo  group The risk factors of various cerebrovascular diseases (atherosclerosis, stroke, hypertension,  coronary heart disease, atrial fibrillation, dyslipidemia, diabetes mellitus) are both risk  factors of Alzheimer's disease and one of the many causes of vascular dementia. There are  many manifestations of mental retardation caused by cerebrovascular diseases. The most  prominent aspect is cognitive and behavioral impairment, which is characterized by mental  retardation, forgetfulness, misunderstanding and poor calculation ability. Yangxue Qingnao  pill (z20063808:) is produced by Tianshili Pharmaceutical Group Co., Ltd, And then improve  the ability of learning and memory. Some clinical application results show that the drug can  significantly improve the cognitive and behavioral ability of patients with ischemic stroke,  improve the cognitive function of patients with mild Alzheimer's disease, and improve the  quality of life. Therefore, this study mainly compared the effectiveness of treatment of  vascular cognitive impairment in three groups, namely, the xidezhen group, the  yangxueqingnaowan group and the placebo group. Inclusion Criteria:  1. Over 50 years old, under 85 years old, male and female, including 50 and 85 years old;  2. The patients agreed to participate in the trial and signed the informed consent.  3. The diagnostic criteria for vascular cognitive impairment without dementia are as  follows:  1. There are risk factors of cerebrovascular disease or the existence of  cerebrovascular disease;  2. The development of cognitive impairment was fluctuating;  3. Mild memory impairment or retention;  4. There is a causal relationship between cerebrovascular disease and cognitive  impairment, and other diseases are excluded;  5. The activities of daily living remained normal;  6. According to the diagnostic criteria of mild cognitive impairment (MCI) developed  by Xiao Shifu, the subjects' MMSE score was less than or equal to 26 Exclusion Criteria:  1. The researchers considered that it was not suitable to be included in the study;  2. Known liver diseases of clinical significance, which may hinder patients from  completing the test, and / or total bilirubin, aspartate aminotransferase, alanine  aminotransferase and alkaline phosphatase are 1.5 times higher than the upper limit of  normal value;  3. The patients with known clinically significant kidney disease may be prevented from  completing the test, and / or the serum creatinine is higher than the normal range in  the laboratory, and / or the blood urea nitrogen is 1.5 times higher than the normal  range;  4. He had a history of acute cerebrovascular disease within 3 months;  5. At present, there is active epilepsy;  6. History of mental illness;  7. Peptic ulcer and gastrointestinal bleeding;  8. Any of the tested drugs was taken within 28 days before medication, which may cause  cognitive changes and important organ damage.  9. Accompanied by unstable blood system and immune system diseases, is not in clinical  remission.  10. Malignant tumor or intracranial tumor is known;  11. Those who had surgery within three months or had a history of trauma.  12. There are other advanced, serious or unstable diseases, which affect the evaluation of  its efficacy and safety;

Improving healthy physiological processes through nutritional intervention, as opposed to  restoring physiology after disease occurrence, is an important new avenue for the reduction  of disease burden in the population. A relatively new target for interventions is the gut  microbiome. Dietary fibre is a nutritional intervention shown to alter gut microbiome and  function. The present study aims to elucidate the relationship between microbiome modulation  with dietary fibre and health. In order to assess health improvement, a meal challenge will  be given to characterize the physiological processes and their resilience to challenge in  healthy volunteers before and after microbiome modulation. The gut microbiome has been extensively implicated as an organ involved in various  physiological processes such as nutrient and drug metabolism, microbial protection and  immunomodulation. The gut microbiome educates the host immune system, promotes homeostasis  and protects against systemic inflammation, among other things through production of  short-chain fatty acids (SCFAs). An altered microbiome is also involved in inducing low-grade  systemic inflammation by translocation of bacterial lipopolysaccharide (LPS) through the  intestinal lining. Additionally, the gut microbiome produces trimethylamine (TMA), which when  oxidized to trimethylamine N-oxide (TMAO) is documented as an indicator of endothelial  dysfunction and cardiovascular health risk. The goal of the present study is to further  clarify the relationship between the gut microbiome, homeostasis, immunity and health. This  will be achieved by introducing an intervention known to alter gut microbiome  characteristics, dietary fibre, and measuring its effect on the gut microbiome on the one  hand and the response to metabolic challenge on the other.  Fibre mixtures consisting of indigestible carbohydrates have been shown to alter the  composition and function of the gut microbiome. Fibre functions as a substrate for  fermentation, creating SCFAs, and as a food source for bacterial commensals regarded as  beneficial. Thus, fibre can shift the balance of microbial species in the gut towards  beneficial commensals and away from potential pathogens. Moreover, these changes in  composition and function of the microbiome can feasibly affect integrity of intestinal  lining, TMA production and various other processes, therefore exerting an effect on low-grade  inflammation, cardiovascular and metabolic health. The gut microbiome can be analysed using  16s RNA sequencing, quantifying the relative abundance of various bacterial species, and by  measuring SCFAs in human plasma, quantifying their production by bacteria in the gut. In this  study, we will integrate a third method to measure the gut microbiome. The I-screen,  developed by TNO, is a platform in which the in vivo microbiome composition can be mimicked  in an in vitro system, allowing for experimental analysis of the effects of compounds and  ingredients on the microbiome. With this method, the processes and conditions affecting  microbiome composition can be assessed more closely, possibly clarifying specific  relationships between intervention and microbiome composition.  The present study aims to assess the effects of this microbiome modulation by evaluating the  response to a metabolic challenge, quantified through measurement of a metabolic and  inflammatory biomarker panel to create a composite outcome called 'resilience'. This  phenotypical flexibility test (PhenFlex, PFT), consisting of a mixed meal with protein, fat  and glucose, induces a systemic response which when analysed allows for sensitive assessment  of subtle health benefits in otherwise healthy subjects. Results of the PFT are presented as  a composite of multiple biomarkers grouped by physiological processes such as inflammation  and liver metabolism, creating the 'axes' of a 'health space'. Earlier research shows that  selected dietary products affected inflammatory processes, oxidative stress and metabolism,  based on dynamic responses after fat load. Other research has shown that the challenge test  concept is able to reveal previously unidentified correlations between specific nutrients and  health-related processes, and that decreased phenotypic flexibility as measured by PFT can be  used to identify people that might benefit from health interventions. Finally, in a human  volunteer study with whole grain wheat products researchers were able to show a positive  effect on diverse composite markers of resilience, including low grade inflammation, after 12  weeks of exchange of refined wheat for whole grain wheat consumption.  By measuring the effect of our intervention on the gut microbiome with several tools, as well  as using the challenge concept for quantifying health, this study is well positioned to  provide insight in the specific mechanisms of interaction between microbiome and host, as  well as create new evidence-based avenues for the improvement of health. Inclusion Criteria:  1. Signed informed consent prior to any study-mandated procedure.  2. Healthy male or female subjects, between 45 and 70 years of age, inclusive.  3. Female subjects must be of non-childbearing potential (postmenopausal for at least 12  months prior to screening or documented surgically sterile).  4. BMI 25-30 kg/m2, inclusive  5. Fibre intake below recommended limits as assessed by dietary fibre intake short food  frequency questionnaire (DFI-FFQ) (16).  6. Has the ability to communicate well with the Investigator in the Dutch language and  willing to comply with the study restrictions. Exclusion Criteria:  1. Evidence of any active or chronic disease or condition that could interfere with, or  for which the treatment of might interfere with, the conduct of the study, or that  would pose an unacceptable risk to the subject in the opinion of the investigator  (following a detailed medical history, physical examination, vital signs (systolic and  diastolic blood pressure, pulse rate, body temperature) and 12-lead electrocardiogram  (ECG)). Minor deviations from the normal range may be accepted, if judged by the  Investigator to have no clinical relevance.  2. Chronic diseases that can affect study parameters, including but not limited to  metabolic syndrome, chronic obstructive pulmonary disease, diabetes mellitus,  auto-immune disease, cardiovascular disease, cerebrovascular disease, gastrointestinal  disease or history of abdominal surgery with removal of (part of) small or large  intestine, or any known condition that can interfere with treatment compliance such as  psychiatric disease or drug dependence.  3. Positive Hepatitis B surface antigen (HBsAg), Hepatitis C antibody (HCV Ab), or human  immunodeficiency virus antibody (HIV Ab) at screening.  4. Systolic blood pressure (SBP) greater than 180 or less than 90 mm Hg, and diastolic  blood pressure (DBP) greater than 120 or less than 50 mm Hg at screening.  5. Abnormal findings in the resting ECG at screening defined as:  1. QTcF> 450 for males or QTcF>470 for females or QTcF < 300 ms;  2. Personal or family history of congenital long QT syndrome or sudden death;  3. Evidence of atrial fibrillation, atrial flutter, complete branch block,  Wolf-Parkinson-White Syndrome, or history of cardiac pacemaker.  6. Use of antibiotics, antacids, laxatives, statins, anti-diarrheal, immunomodulatory or  antidiabetic medication <3 months before start of study.  7. Use of any medication or vitamin, mineral, herbal, and dietary supplements within 7  days of study product administration, or less than 5 half-lives (whichever is longer).  Exceptions will only be made if the rationale is clearly documented by the  investigator.  8. Vegan, macrobiotic, slimming or medically prescribed diet up to 3 months prior to the  first administration.  9. History of food allergies or intolerances or any confirmed significant allergic  reactions (urticarial or anaphylaxis) against any drug or multiple documented drug  allergies.  10. Participation in an investigational drug or device study within 3 months prior to  first dosing.  11. History of abuse of addictive substances (alcohol, illegal substances) or current use  of more than 21 units alcohol per week, drug abuse, or regular user of sedatives,  hypnotics, tranquillisers, or any other addictive agent, or positive test for drugs of  abuse at screening or pre-dose.  12. Active smoker up to 15 years prior to the screening visit.  13. Loss or donation of blood over 500 mL within three months (males) or four months  (females) prior to screening or intention to donate blood or blood products during the  study.

New advances in information computer technology and artificial intelligence (AI) offer the  possibility to create a personalized tool and support system for healthy living and eating,  and this is the principal objective of the PROTEIN Project (an EU-funded consortium; Horizon  2020). In order to obtain information on the acceptability, usability and its effectiveness  at facilitating behaviour change of the application within the home and store. A pilot trial  will be conducted in participants who are overweight (BMI 25-29.9 kg/m2) and a separate group  of participants who consume a low quality diet (low in fruit and vegetable intake) and/or  have a nutrition deficiency (specifically iron-deficiency anaemia).  During this study the subjects will be asked to attend the lab (or remotely due to covid  restrictions) at the beginning of the study for baseline measurements and instructions on how  to use / download the mobile application. Participants will have their anthropometrics  measured (including height/ weight/ waist: hip circumference). The PROTEIN application will  collect self-reported data from the user, which includes: user profile input, dietary and  fluid intake, daily physical activity (such as step count), biochemistry, sleep and chewing  (in- meal behaviour). Information on how users will interact with the app, which screens they  use, how many log ons and how often data is inputted will also be collected. Throughout the  trial, the participants will be contacted via the application or by the researchers to  request feedback on their progress and to encourage reporting of any issues.  Health care professionals will also be recruited to test the expert dashboard of the PROTEIN  app. Through this system they will be able to provide nutrition/ physical activity advice  directly to their patients and input their relevant biochemical results (such as haemoglobin  for anaemic patients). During this study the subjects will be asked to visit the lab followed between 4 and 16 weeks  usage of the PROTEIN app and then a final lab visit.  In the event that COVID-19 restrictions continue and prevent, or restrict, face-to-face  visits a completely remote study protocol will also be developed and used in place of the  study below.  1. Advertising and Recruitment:  i) General public: Prospective users will be recruited by the University of Surrey via  social media (e.g. Facebook and Twitter), posters and flyers in the local area and  emails sent to University staff and students. With the permission on the relevant group  leaders,' overweight participants will be recruited via local commercial weight loss  groups. With the permission of the practice managers recruitment via GP practices will  also be undertaken, with practice registers screened by a member of practice staff and  information/ invitation letters sent to those who meet the inclusion criteria (no  details will be shared with the research team). Flyers will also be distributed to local  relevant outpatient clinics, e.g. haematology and dietetic with the permission of the  clinic managers.  Participants will also be recruited through health care professionals (HCP) in the local  area following identification of suitable HCPs (see below)  ii) Health Care Professionals (HCPs):  HCPs involved in supporting the dietary or activity goals of target clients will also be  recruited to the HCP arm of the study. The project will be promoted through local (and,  if remote, National) professional networks and professional body membership lists,  newsletters and via relevant social media channels. HCPs will have the option to  participate in a desk-based expert review of the application (without registering  specific clients) with respect to its usability or to register one or more of their own  clients on the app via the user dashboard to participate in the efficacy review. In the  latter case suitable clients identified by the HCP will be required to also register  with the trial. The HCP will be provided with flyers and invitation letters to allow  them to make first contact with the client who will be asked to contact the research  team to confirm their willingness to participate, ensuring no personal data is shared  prior to consent being received.  2. Baseline measurements:  i) Public, Face to face: Users will attend the lab and will then have their body  composition measured (to include their height, weight, waist and hip circumference) by  the researchers.  ii) Public, Remote: An alternative remote protocol will utilise Zoom/ Microsoft teams  video call. These will be arranged by the researchers with the participants to take them  through self-completion of the baseline measures and procedures.  iii) HCPs: HCPs will be contacted via email and will also be invited to either attend  the lab or meet with the researchers utilizing Zoom/ Microsoft teams to discuss the  usage of the expert dashboard.  3. PROTEIN app usage for public:  Following this, the users will be requested to log the following details to set-up the  PROTEIN system: contact details (name/ email/phone number), age, gender, height, weight,  ethnicity, morbidity status (such as cardiovascular disease/ diabetes mellitus etc.),  education/ socioeconomic status, smoking status, diet or drink habits (such as  vegetarian/ vegan/ dairy-free etc.), and medication.  Daily food and fluid intake will be collected via the PROTEIN app and will be  self-reported by the user/ participant.  Users will be asked to log all dietary and fluid intake for 7 days per week (to include  the weekend) into the home PROTEIN application suite.  Users will either use their respective smartwatches/activity trackers or manually input  the relevant data into the home PROTEIN application suite. In the former case, physical  activity and sleep data will be collected in daily summaries as provided by Google Fit  (or a suitable alternative, such as Garmin, FitBit, Polar, Apple watch etc.).  Smart watches may be provided free of charge for a subset of users (subject to trial  resources) and there may also be an opportunity for participants to use their own  existing smartwatches. In the latter case, users will be requested to manually log daily  activity data, for 7 days per week.  Users will be monitored by the PROTEIN artificial intelligence (AI) system for  deviations from their suggested plan and for any meal or activity swaps requested to  check for adherence/ compliance to the recommendations suggested by the PROTEIN AI  system.  A subset of users who are also registered with OCADO will receive food shopping  recommendations (in the form of a shopping list) tailored to their nutritional  requirements and targets; budget will also be taken into account. Participants will be  asked to indicate all food products that they swapped/ bought and for whom they bought  them within the PROTEIN application suite. This will be conducted in partnership with  OCADO.  4. After at least 4 weeks of usage, data will be collected regarding the user and HCP  experience via an online questionnaire through the PROTEIN app or sent usability  questionnaires via email by the researchers.  5. Follow-up measures:  i) Public, Face to face: Users will attend the lab after at least 4 weeks of usage and  will then have their body composition remeasured (to include their height, weight, waist  and hip circumference) by the researchers. They will also be asked to provide feedback  on the usability of the application by completing two questionnaires on the 1) usability  of the application and 2) suitability for general public use.  ii) Public, Remote: An alternative remote protocol will utilise Zoom/ Microsoft teams  video call. These will be arranged by the researchers with the participants to take them  through self-completion of the follow-up measures following at least 4 weeks of usage.  Participants will be asked to provide feedback via two online questionnaires on the 1)  usability of the application and 2) suitability for general public use.  iii) HCPs: HCPs will be contacted via email and will also be invited to either attend  the lab or meet with the researchers utilizing Zoom/ Microsoft teams to discuss their  feedback following usage of the expert dashboard for at least 4 weeks. They will be  asked to provide feedback via two questionnaires on the 1) usability of the application  and 2) suitability for usage by health care professionals.  A subset of participants (from all groups), representing both those who have engaged or  not with the app, will also be contacted by the researchers after their trial period has  ended and invited to take part in additional qualitative measures, such as focus group  interviews to provide more feedback on their experience of the PROTEIN app. Inclusion Criteria:  Overweight group:  -  ≥ 18 years of age  -  BMI: 25 - 30 kg/m2  -  In good physical health  -  Not a regular user of another nutrition support application (such as MyFitnessPal)  -  Able to provide written informed consent  -  Android Smart Phone/ Tablet user  Individuals with poor quality diet  1. deficiencies:  -  ≥ 18 years of age  -  Diagnosed iron deficiency  -  In good physical health  -  Not a regular user of another nutrition support application (such as  MyFitnessPal)  -  Able to provide written informed consent  -  Android Smart Phone/ Tablet user Individuals with poor quality diet  2. low fruit and vegetable intake:  -  ≥ 18 years of age  -  Low fruit and vegetable intakes (< 2-3 portions/ day)  -  In good physical health  -  Not a regular user of another nutrition support application (such as  MyFitnessPal)  -  Able to provide written informed consent  -  Android Smart Phone/ Tablet user  Health care professionals  -  Registered health care professional; General Practitioner/ Dietitian/ Nutritionist/  Registered Exercise Professionals (REPs) etc who sees clients for assistance with  weight management and/ or iron deficiency or diet quality.  -  Willing to trial a new nutrition support application with their patients  -  Android Smart Phone/ Tablet user Exclusion Criteria:  Overweight group:  -  Those who have been diagnosed with cardiovascular disease, type 1 diabetes mellitus or  type 2 diabetes mellitus.  -  Currently receiving treatment for long term medical conditions  -  Clinically significant haematological abnormalities or an active malignancy  -  Regular exercisers (more than 150 minutes of moderate exercise per week or > 75  minutes of high intensity exercise)  -  People who are unable to exercise for medical reasons or for whom exercise is  otherwise contra-indicated by a health professional  -  People with disordered eating (such as anorexia nervosa etc.)  -  Those who are not be able to provide written consent.  -  Those who are unable to read/write sufficiently to provide consent and complete study  materials  Individuals with deficiencies and poor-quality diet:  -  Those who have been diagnosed with cardiovascular disease, type 1 diabetes mellitus or  type 2 diabetes mellitus.  -  Currently receiving treatment for long term medical conditions.  -  Clinically significant haematological abnormalities or an active malignancy  -  Regular exercisers (more than 150 minutes of moderate exercise per week or > 75  minutes of high intensity exercise)  -  People who are unable to exercise for medical reasons or for whom exercise is  otherwise contra-indicated by a health professional  -  People with disordered eating (such as anorexia nervosa etc.)  -  Those who are not be able to provide written consent.  -  Those who are unable to read/write sufficiently to provide consent and complete study  materials  Health Care Professionals:  -  Not affiliated/ registered health care professional  -  Do not have any clients/ patients that fall into one of the groups above (overweight,  iron deficiency or low fruit/ vegetable consumption).

The small insulinoma can not be detected by the CT or MRI. We use 68Ga-NOTA-exendin-4  positron emission tomography/computed tomography (PET/CT) to detect the insulinoma for the  patient diagnosed with endogenous hyperinsulinemic hypoglycaemia. And the diagnostic value  will be performed. A single dose of 37-111 Mega-Becquerel (MBq) 68Ga-NOTA-exendin-4 will be  injected intravenously. Visual and semiquantitative method will be used to assess the PET/CT  images. The glucagon-like peptide-1 receptor (GLP-1R) is an emerging target due to its high  expression in benign insulinomas. 68Ga-NOTA-exendin-4 is an optimal probe targeting GLP-1R.  The clinical use of 68Ga-NOTA-exendin-4 PET/CT in detecting insulinomas will be evaluated.  And the comparation between PET diagnostic value and CT / MRI will be done. Inclusion Criteria:  -  1.age ≥6 years old 2.Patients with hypoglycaemia 3.Endogenous hyperinsulinemic  hypoglycaemia 4.Enhanced CT or MRI within 1 month 5.Signed written consent Exclusion Criteria:  -  1. Breast feeding 2.Pregnancy or the wish to become pregnant within 6 months 3.Renal  function: serum creatinine during 41-73umol/L 4.Any medical condition may  significantly interfere with study compliance; 5.Known allergy

Cognitive difficulties can affect many people who live with multiple sclerosis (MS). These  difficulties, such as within thinking, memory, and problem solving, can have an impact on  important aspects of an individual's life, including their daily activities, work, and how  they manage their condition. Previous studies have suggested that cognitive difficulties  affect approximately 40-70% of people living with MS, yet there are currently no treatments  to target these problems. Recent research has directed towards a non-invasive intervention  which stimulates a part of the brain (called the dorsolateral prefrontal cortex, or DLPFC for  short) which is reported to participate in cognitive processes, such as memory, thinking, and  attention. This intervention, called "intermittent theta burst stimulation" (iTBS), involves  placing a magnetic device to the skull to activate the DLPFC underneath. This technique has  been used successfully in the treatment of depression and is widely considered safe and  painless. Previous studies have also shown that iTBS intervention can lead to improvements in  cognitive processes.  Before the investigators can progress to a large trial to explore its clinical effectiveness  for reducing cognitive problems for people with MS, some aspects regarding its feasibility  need to be clarified, for example whether it is an acceptable and tolerable intervention for  people living with MS. A single-centre, mixed methods feasibility randomised controlled trial  will be conducted to compare four groups (10 participants each) of iTBS administration. At  baseline, End of Intervention (EOI), and 8-week follow up, the investigators will complete  outcome measures to evaluate cognition, mood and fatigue. Participants will also undergo MRI  scans at baseline and EOI. Following participation, participants will be interviews and the  investigators will organise a post-participation workshop to explore their experiences of the  trial, including the tolerability of the protocol and acceptability of the visit schedule,  and any differences in cognition. The primary objective is to assess the feasibility of the trial procedures, in terms of their  acceptability and tolerability for pwMS who have cognitive impairment. For this aim, the  completion of the intervention schedule will be measured (e.g., attending all sessions per  the protocol, considering any missed appointments and reasons for non-attendance where  possible) including the end of intervention assessments, as well as the 8-week follow up to  ascertain participant willingness to complete the full study.  Participants will be randomly allocated to one of four groups (Group 1: 4 administrations of  intermittent theta burst stimulation (iTBS) over 1 week; Group 2: 8 administrations of iTBS  over 2 weeks; Group 3: 16 administrations of iTBS over 4 weeks; Group 4: 8 administrations of  sham iTBS over 2 weeks). Participants will not be aware whether they have been allocated to  receive active or sham iTBS administration.  Intervention - Active iTBS: Active connectivity-guided iTBS will be administered to the left  dorsolateral prefrontal cortex (DLPFC). The administration comprises bursts of 3 pulses at  50Hz with a power of 80% motor threshold, at a burst frequency of 5 Hz (i.e., every 200ms)  for 2 seconds, repeated every 10 seconds for a total of 190 seconds (600 pulses). Blocks are  repeated a total of 3 times, with 5 minutes rest intervals between blocks. (Duration and  frequency: 30 min, 4 times a week for up to 4 weeks depending on group).  Sham iTBS: The sham iTBS administration is performed under the same conditions and with an  identical protocol and equipment to the full administration, except that it uses a  commercially available sham iTBS coil designed for use in double-blind trials. This sham coil  looks like the real coil and connects to the iTBS unit but delivers only a very weak and  shallow stimulation thus simulating the sounds made by the real iTBS coil.  At baseline, End of Intervention (EOI), and 8-week follow up, outcome measures will be  completed to evaluate cognition, mood and fatigue. Participants will also undergo MRI scans  at baseline and EOI. The purpose of the MRI is to allow identification of the exact location  over which the iTBS intervention will be applied, and it will allow measurement of brain  function before iTBS intervention (or sham).  The MRI scan will include:  -  High resolution T1-weighted structural brain image for image co-registration,  -  Resting-state functional MRI (rs-fMRI) for connectivity-guided neuronavigation,  -  Fluid attenuated inversion recovery (FLAIR)  -  Diffusion tensor imaging (DTI) acquisitions to quantification spatial mapping of macro-  and mircrostructural white matter injury,  -  Arterial Spin Labelling (ASL) perfusion imaging to map cerebral blood flow.  -  Task related functional MRI - N-Back task.  The investigators have developed a questionnaire to explore tolerability and acceptability of  the procedures, and participants will also be invited to discuss their experience of  participating in the trial at interview 8 weeks post-intervention.  Finally, at the end of the study, the investigators aim to host a post-participation workshop  at the beginning of month 28, following collection and analysis of main outcomes. Depending  on covid-safe recommendations from the government and university, this may be via video call  or at a venue. All participants will be invited to discuss whether the experience of  participation (varying from 1-week to 4-weeks) can inform which of intervention regime  investigators should take forward into a subsequent pilot trial, to expand on the preliminary  data analysis from the qualitative interviews. Investigators will explore the magnitude and  nature of the effect on cognition that would be needed to be achieved to give a meaningful  change to them personally, such that the iTBS interventions of different durations would be  warranted. For example, participants may feel that only a major improvement in day-to-day  cognition would justify a 4-week intervention, whereas others may feel that any benefit would  justify this. These issues will be explored to inform future trial design. Inclusion Criteria:  -  Aged between 18 - 69 years.  -  Received a diagnosis of MS (any type of MS) at least 12 months prior to baseline  assessment.  -  Report cognitive problems, as determined by a cut-off score of 55 or lower on the oral  SDMT  -  Ability to give informed consent  -  Able to commit to regular attendance in clinic, for up to 4 times a week for 4 weeks  and follow up appointment eight weeks after the end of trial procedures. Exclusion Criteria:  -  Diagnosed with depression or scores ≥15 on the Patient Health Questionnaire-9  -  Medical history of, or self-reported, seizures  -  Neurological conditions (in addition to MS), e.g., brain neoplasm, cerebrovascular  events, epilepsy, prior brain injury or brain surgery  -  Contraindications to MRI scanning (identified by standard MRI safety screening  questionnaire).  -  Contraindications to TMS, including hairstyles or piercings that would impair magnetic  transmission which cannot be altered to ensure effective intervention  -  Frequent panic attacks which are likely to prevent regular attendance or participation  in MRI/TMS procedures  -  Prior TMS intervention  -  Pregnancy  -  MS relapse within the preceding 6 weeks  -  Significant mobility problems if they are likely to preclude regular attendance in  clinic, for up to 4 times a week for 4 weeks  -  Involved with any other clinical trials involving medical procedures, interventions or  treatment.

Preterm birth (PTB) occurs before 37 weeks of gestation and is a major cause of neonatal  mortality and morbidity. PTB results from heterogeneous influences. One of them is the  inherited predisposition of spontaneous PTB, and another is the change in the placental  microbial composition as this can cause infections, which lead to inflammation, a common  cause of preterm birth. Interestingly, maternal periodontal disease is an independent risk  factor for PTB, low birth weight and fetal growth restriction. Immune responses to infectious  events or inflammation as well as genetic predisposition to inherited conditions have  successfully been studied by using assessing genetic expression profiling. The molecular  signature is sets of genes, proteins, genetic variants or other variables that can be used as  markers for a particular phenotype.  Child morbidity from malnutrition resulting in poor growth and stunting remains a major  public health issue that affects the local population just like PTB. While risk factors for  malnutrition are multifaceted, there is also a hypothesized causal link between early gut  microbiome disruption that leads to chronic malnutrition in otherwise healthy infants.  Molecular signatures including the intestinal microbiome development of preterm infants will  be evaluated and compared to the term (≥37 weeks' gestation) counterparts. Moreover, a  comprehensive examination of possible factors associated with poor growth and poor motor- and  neurodevelopment will be assessed.  In this extension study: The primary goal for the child is to evaluate the perturbation in  the development of the genomic profile including intestinal microbial habitat from children  in a rural and limited-resource setting from birth to two years of life. Rationale:  The importance of early life epigenetics is now recognized to have direct implications for  health in later life and a consistent limitation expressed in peer reviewed publications has  been the small sample size of the studies. Rather than establish a separate cohort to study  epigenetics in young children in this environment this extension study of TMEC 15-062  (Molecular signature of Karen and Burmese women on the Thailand--Myanmar border) aims to  build on the detailed sampling of the mothers to not only identify biomarkers of preterm  labor but also to understand high rates of stunting and anaemia in this area, and possibly  develop predictive tools or pave new ways for prevention in the future.  Moreover, a non-invasive intervention in the form of nutrition and WASH counselling may  provide information on whether this form of engagement can positively influence child  development, prevent malnutrition and whether perturbations in the infants molecular  signature can be observed.  In addition, the mothers exposed to the sampling procedure at birth in this study will be  able to make a well-informed decision about whether they wish to enrol the child in such a  study.  The rationale for the planned samples in children born to mothers who participated in the  TMEC 15-062 study are summarized in the following text:  Child gut microbiome and assessment of nutrition from stool samples (Risk-none) The  intestinal ecosystem is very dynamic, especially in the first period of life, as it needs to  evolve from scratch, hence investigators want to follow children and analyse stool samples in  first 24 month of life. investigators propose to assess what kind of impact the gut  microbiome has on the child's growth and development. Since exposure to helminths is common  in the study population, children stool samples will also be used to examine for helminthic  infestations.  This point would also include a home visit as part of nutrition evaluation by questionnaire  and direct observation (food preparation including hygiene, child food content, feeding  patterns) to relate to microbiome.  Early childhood Transcriptome from capillary blood (Risk-minimum) This point will enable us  to understand whether preterm infants have different gene expression than their term  counterparts and if so, how it evolves in the early period of life. Moreover, specific  signals for children at risk for or suffering from malnutrition or stunting resulting from  gastrointestinal inflammation or barrier disruption could be picked up. Total blood 0.85 mL  in 2 years.  Early childhood detection of anaemia from capillary blood (Risk-minimum) Anaemia will be  treated and iron supplement effect on gut microbiome analysed. Total blood 0.85 mL in 2  years.  Early childhood detection of soil transmitted helminth infection from stool sample  (Risk-none) Helminth infection will be treated and the effect on gut microbiome analysed.  Stool sample each visit.  Child growth assessment and evaluation of motor and neurocognitive development (Risk-none)  Premature infants have a higher risk for lifelong health and development problems.  Investigators propose to follow the children's over the period of 2 years to assess their  growth and their neurocognitive and motor development. Preterm children's growth and  development will be compared to term neonates. The recommended schedule of growth assessment  in healthy children is (1, 2, 4, 6, 9, 12, 18, 24 months). In this study children will be  followed more frequently: monthly in the first year of life and 3 monthly in the 2nd year of  life (1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 15, 18, 21, 24 months). The reasons for this  include: the objective of the root study TMEC 15-062 which is on preterm infants who require  closer follow up, to relate perturbations of biomarkers to stunting, and in this mobile  population scheduled visits may be missed so a more flexible arrangement for checking  anthropometry at any monthly visit in the first year of life reduces the chance that poor  growth is not identified.  In addition, the growth and development of children born to mothers who had a febrile episode  during pregnancy will be compared to children whose mothers did not experience fever episodes  during pregnancy.  Children with poor growth or malnutrition will be given supplementary nutrition and nutrition  advice will be given to the mother.  Grant reference number: B9R01250 Inclusion Criteria:  -  Karen or Burmese pregnant woman in study TMEC 15-062 who are willing to have their  offspring (children) comply with all study requirements  -  Pregnant woman is willing and able to give informed consent for her child to  participate in this study  -  Mother enrolled to MSP (TMEC 15-062) and child enrolled in MSP_Ext (TMEC 17-008)  -  Term pregnancy (gestational age ≥37 weeks)  -  Clinic birth  -  Normal new-born  -  Post-partum mother willing to have home visits  -  Post-partum mother willing and able to give informed consent to participate in this  study Exclusion Criteria:  -  Children (in the investigators opinion) with any social or physical condition which  would make it difficult to comply with study requirements  -  Lives too far to make home visits feasible  -  Home situation unstable and likely to move before the child is 9 months old  -  Social situation that would make it difficult for the mother to comply

To estimate the pulmonary response microvascular thrombosis in critical patients due to  SARS-Cov-2., at the Hospital General de México "Dr. Eduardo Liceaga", a 15 patients  compassionate treatment study was authorized and approved by the ethics and research  committee DI-222-2020. Because of the severity of the illness the legal representative sign  informed consent in all the patients for performing in-situ thrombolysis with alteplase  selectively by catheter in each main pulmonary artery, under fluoroscopic guidance and  acquiring images with the iFlow software to assess immediate and post-procedure response. The main clinical characteristic of patients with severe SARS-Cov-2 infection is hypoxemic  respiratory failure that requires Mechanical Ventilation. The Acute Respiratory Syndrome  model has been proposed as the cause of this significant deterioration in lung function and  all management has focused on ventilatory support management. As for ventilatory failure, it  has been attributed to the presence of severe pulmonary inflammation evolving to fibrosis,  which is the clinical characteristic of patients with Primary Respiratory Distress Syndrome  (which would be the case of this as it is considered a respiratory virus).  Several autopsy studies demonstrated microthrombi in pulmonary circulation. The major  limitation of these investigations is that the autopsy provided static information. Some of  these alterations could be secondary to the disseminated intravascular coagulation (DIC)  observed as the standard route to the multisystem organ failure exhibited in critically ill  patients.  With this comes the contradictory results of high doses of anticoagulants in the survival of  these patients. This intermediate to high doses can reduce organ support treatments in  moderate cases, however, in critically ill patients the benefit of high dose of  anticoagulants, once again failed to produce benefit on survival. Different publication on  biopsies made in these patients have report the presence of thrombosis in the  microcirculation and finally recently has been published the demonstration by direct  examination with Citoscam, the presence of this thrombosis of the microcirculation in vivo in  11 of 13 test (85% of the sample). Studies performed with viscoelastic coagulation tests  present evidence of three key alterations in coagulation  1. EXTEM and INTEM Hypercoagulable states represented by a maximum amplitude (A5, A10 and  MCF) greater than 70mm, short clot formation time.  2. Hyperfibrinogenemia A5 A10 MCF in FIBTEM greater than 30mm  3. Absence of fibrinolytic activity (ML% Lys 30 and Lys 60) 100% Taking this into account  plus the large number of publications regarding the thrombotic phenomenon of the patient  with COVID-19, this could be explained by the presence of a phenomenon of ventilation  perfusion (V / Q) that is observed in patients with Massive Pulmonary Thromboembolism  (PE) which is known as the infinite relationship, that is, the lung is with normal  aeration, but no perfusion, there is no adequate gas exchange, with presence of hypoxia,  increment of death space and ultimately obstructive shock.  In patients with COVID-19, this phenomenon is observed in patients with absence of massive or  submassive PE that explains this phenomenon.  The high mortality of critically ill patients with SARS-Cov-2 infection, the presence of  thrombosis of the microcirculation and the lack of efficacy of anticoagulation in some cases  suggests that this phenomenon could be the cause of the behavior between perfusion  ventilation observed in SARS-Cov-2 patients.  For these reasons, a probe of concept research was developed to find out if pulmonary  perfusion alteration by microthrombosis and secondary V / Q abnormalities could be linked to  the pathophysiology of the patient with severe SARS-Cov-2 infection.  To estimate the pulmonary response microvascular thrombosis in critical patients due to  SARS-Cov-2., at the Hospital General de México "Dr. Eduardo Liceaga", a 15 patients  compassionate treatment study was authorized and approved by the ethics and research  committee DI-222-2020. Because of the severity of the illness the legal representative sign  informed consent in all the patients for performing in-situ thrombolysis with alteplase  selectively by catheter in each main pulmonary artery, under fluoroscopic guidance and  acquiring images with the iFlow software to assess immediate and post-procedure response. Inclusion Criteria:  Patients with severe Covid 19 nfection, from 18 to 75 years old, Invasive Mechanical  Ventilation (IMV) Pao2 / fio2 less than 150 Non réponse to prone position Coagulation  criteria ISTH score >5, D-dimer greater than 1200, Viscoelastic testing EXTEM A5 >65 FIBTEM  > 30 and EXTEM ML<8%  - Exclusion Criteria:  Ischemic CVD or presence of abnormal neurological examination. Active bleeding. Acute  Myocardial Infarction within the previous three weeks or cardiac arrest during  hospitalization.  cardiac tamponade. endocarditis. uncontrolled hypertension SBP> 185mmhg or DBP> 110.  history of stage 4 cancer. history of brain tumor. Arterious venous malformation ruptured  aneurysm. major surgery in the previous 2 weeks major trauma in the previous 2 weeks.  pregnancy. fibrinogen less than 200 blood dyscrasias thrombocytopenia less than 30,000  -

Early stage Parkinson disease (PD) is characterized by a 'honeymoon' phase in terms of  responsiveness of motor symptoms, including gait, to dopaminergic pharmacotherapy. Advancing  PD is associated with disabling axial motor complications, such as freezing of gait (FoG),  with decreased or even refractory dopamine responsiveness in over 50% of patients. The  management of dopamine resistant gait problems represents the most important unmet need in  PD. This study will related detailed motor testing to brain PET imaging to see if certain  molecules (or lack thereof) involved with neurologic transmission in the brain are involved  with FoG. Early stage Parkinson disease (PD) is characterized by a 'honeymoon' phase in terms of  responsiveness of motor symptoms, including gait, to dopaminergic pharmacotherapy. Advancing  PD is associated with disabling axial motor complications, such as freezing of gait (FoG),  with decreased or even refractory dopamine responsiveness in over 50% of patients. The  management of dopamine resistant gait problems represents the most important unmet need in  PD. At present, there is no biomarker of FoG in patients with PD as there is a lack of  mechanistic understanding of dopamine nonresponsiveness of FoG. The investigators have  previously identified cholinergic denervation as a prominent factor related to both falls and  gait slowing in PD. The investigators recently identified that cortical -amyloid deposition  not only associates with cognitive decline but also with postural instability and gait  difficulties in PD. In this proposal, the investigators present preliminary data suggesting  that FoG is associated with either cholinopathy, amyloidopathy or both in PD. The  investigators propose to test the novel hypothesis that comorbid amyloidopathy may be a  possible mechanistic factor underlying the poor response of FoG to dopaminergic therapy in  advancing PD. In contrast, isolated cholinopathy would be expected to be associated with  preserved dopamine responsiveness of FoG. For this purpose, the investigators propose to  perform detailed motor, including FoG, testing in PD patients "on" and "off" their  dopaminergic medications and relate this to dopaminergic 11C-DTBZ, vesicular acetylcholine  transporter 18F-FEOBV and -amyloid 11C-PIB brain PET imaging in PD subjects with and without  FoG. Furthermore, based on recent clinical observations that serotoninergic drugs, like the  popular anti-depressant SSRI drugs, are associated with significantly lower build- up of  -amyloid plaques in the elderly population, and based on the investigators' subsequent  observation of an intriguing inverse relationship between -amyloid plaque deposition and  striatal serotoninergic terminal in PD, the investigators propose to perform an exploratory  sub-study to test a new hypothesis that PD subjects with FoG will exhibit not only higher  striatal -amyloid but also lower striatal serotoninergic innervation (as determined by  11C-DASB serotonin PET imaging) compared to PD subjects without FoG. If confirmed, positive  findings in this study would allow the identification of different PD subgroups  ('personalized medicine'), such as presence amyloidopathy or cholinopathy, to select patients  for targeted pharmacotherapies to potentially prevent the development of FoG (anti-amyloid,  such as serotoninergic drugs) or manage its clinical manifestation (cholinergic augmentation  therapy) in order to preserve and maintain a good quality of life in individuals with PD. Inclusion Criteria:  -  PD based on the United Kingdom Parkinson's Disease Society Brain Bank  -  Diagnostic Research Criteria with or without Freezing of Gait  -  Duration of Disease > 5 years  -  MMSE > 23 Exclusion Criteria:  -  Dementia  -  Dementia with Lewy Bodies  -  Other disorders which may resemble PD  -  Subjects on neuroleptic, anticholinergic (trihexiphenidyl, benztropine) or  cholinesterase inhibitor drugs  -  Evidence of a stroke or mass lesion on structural brain imaging (MRI)  -  Participants in whom MRI is contraindicated including, but not limited to:  -  those with a pacemaker  -  presence of metallic fragments near the eyes or spinal cord  -  cochlear implant  -  Severe claustrophobia precluding MR or PET imaging  -  Subjects limited by participation in research procedures involving ionizing radiation  -  Pregnancy

A study to evaluate the bioequivalence of abaloparatide between 2 abaloparatide-sMTS  treatments 300 μg treatments applied to the thigh for 5 minutes. This is a single site, open-label, randomized, 4-period crossover study to evaluate the  bioequivalence of 2 abaloparatide-sMTS 300 μg treatments (Patheon sterile abaloparatide-sMTS  and Kindeva ultra-low bioburden abaloparatide-sMTS) applied to the thigh for 5 minutes. The  study will also evaluate the effect of small deviations in the wear-time of the Patheon  abaloparatide-sMTS worn for 4 minutes or 7 minutes compared to the Patheon abaloparatide-sMTS  worn for the prescribed 5 minutes. Inclusion Criteria:  -  Female subjects aged 40 to 65 years old, inclusive, at Screening  -  Good general health as determined by medical history and physical exam (including  vital signs, and has a body mass index between 18 and 34 kg/m^2 inclusive)  -  Laboratory tests within the normal range  -  Serum 25-hydroxyvitamin D values must be > 20 ng/mL Exclusion Criteria:  -  Presence or history of any disorder that may prevent the successful completion of the  study.  -  Diagnosed with osteoporosis, Paget's disease, or other metabolic bone diseases (eg,  vitamin D deficiency or osteomalacia), or had a non-traumatic fracture within 1 year  prior to the initial screening;  -  History of any cancer within the past 5 years other than squamous or basal cell  carcinoma;  -  History of allergy to abaloparatide or drugs in a similar pharmacological class;