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The purpose of this study is to assess the efficacy and safety of Ru Yi Jin Huang Powder for  the treatment of Colles' fracture. According to the definition of the World Health Organization, Taiwan officially entered the  aged society in 2018. The population over the age of 65 exceeds 14% of the total population.  Based on this, it is estimated that we will enter a super-aged society in 2026. Because the  older the age, the higher the rate of bone loss, and the higher the risk of osteoporosis, the  easier it is to fracture due to falls. The incidence of bone fracture is directly  proportional to the aging population. Traditional Chinese Medicine(TCM) interventional  fracture treatment has a long history and experience.  Many recent studies show that TCM is benefit to reduce risk of total hip replacement and has  a positive influence on the prevention of osteoporotic fracture. In drug mechanism research,  some Chinese herbal medicine has been proved to promote bone fracture healing . Although most  of these researches have been confirmed in the laboratory, little information is available on  true patients. In clinical we observe a lot of topical Chinese medicine been used after  fracture, so the purpose of this thesis is to investigate the effective of topical Chinese  herbal paste. This study may lead to build the usage of guideline after fracture. Inclusion Criteria:  1. People who are over 20 years old and have no lack of mental ability can understand the  content of the experiment and are willing to participate in it.  2. Patients with Colles' fracture receive surgical fixation(ORIF). Exclusion Criteria:  1. People are unable to cooperate with experiments and fill out questionnaires.  2. Patients have wounds on the back of their wrists.  3. Patients are allergic to traditional Chinese medicine for external applications or  have used other traditional Chinese medicine for external applications.  4. Patients have cancer, stroke, and systemic diseases such as severe anemia, thyroid  disease, uncontrolled diabetes, etc.  5. Pregnant woman.

The goal of this cross over study is to investigate the effect of short term time restricted  eating (TRE) on the innate immune system in patients with a history of myocardial infarction. In the recent years, research has shown the prominent role of low grade systemic inflammation  in cardiovascular disease (CVD) and the crucial role myeloid cells, mainly monocytes and  macrophages, play in atherogenesis. Time restricted eating (TRE), i.e. eating the normal  amount of calories within a limited time period per day, has a beneficial effect on multiple  factors involved in the development of CVD, such as blood pressure, heart rate, lipid and  blood glucose levels, and insulin sensitivity. TRE also reduces markers of systemic  inflammation and reduces the number of circulating monocytes.  It is now hypothesized that TRE reduces the pro-inflammatory monocyte phenotype of patients  with a history of myocardial infarction. Therefore, the investigators will perform a  exploratory prospective randomised open label blinded endpoint cross-over study to  investigate the effect of short term TRE on the innate immune system in patients with a  history of myocardial infarction. Inclusion Criteria:  -  Adult (age >18 years)  -  Diagnosed with a myocardial infarction (between 1 and 5 years ago)  -  Body mass index between 20 and 35 kg/m2  -  Able to understand, be motivated and follow the study related procedures  -  Able to understand and give written informed consent Exclusion Criteria:  -  Myocardial infarction (defined as an increase in cardiac enzymes in combination with  symptoms of ischemia or newly developed ischemic ECG changes), coronary artery bypass  graft surgery or other major (cardiovascular) surgery, stroke or transient ischemic  attack (TIA) in the past 1 year prior to screening.  -  Use of immunomodulatory drugs  -  Use of drugs that need to be taken with food.  -  Diabetes Mellitus type I and type II  -  Medical history of any disease associated with immune deficiency (either congenital or  acquired, including chemotherapy, active malignancy, organ transplant) or auto immune  disease  -  Clinically significant infections within 1 months prior to start of or during  intervention period or control period (defined as fever >38.5).  -  Vaccination <1 month before start of or during intervention or control period.  -  Eating disorders

The goal of this clinical trial is to the use of VRi specified effects on pain,  kinesiophobia, fear of pain, disability, self-efficacy, grip strength and range of motion in  motion in people with chronic shoulder pain. The main question[s] it aims to answer are:  -  Can specific immersive virtual reality software decrease movement-evoked pain in  patients with chronic shoulder pain compared to non-specific software?  -  Can specific immersive virtual reality software increase shoulder flexion range of  motion in patients with chronic shoulder pain compared to non-specific software?  Participants will use a specific VRi software compared with non-specific VRi software Studio Design Randomized controlled clinical trial (RCT). This protocol follows the  indications of the guidelines for Clinical Trial Publications (CONSORT) and will follow the  TIDIER check-list for the exhaustive description of the interventions that will be performed.  Target population Patients with persistent musculoskeletal shoulder pain aged 18-65 years  primary chronic musculoskeletal pain, according to the International Classification of  Diseases-11 (2019) of the International Association for the Study of Shoulder-related Pain  (IASP).  Sample size calculation A total of 30 individuals for each treatment group will allow to  detect, in numerical variables, differences between pairs of group means of a magnitude  (Visual Analogue Pain Scale) corresponding to 1.5 points of the standard deviation, with an  effect size of 80% maintaining the type I error at a level of 5%. Taking into account a loss  of 10%, it would be necessary to include 33 individuals in each group.  Interventions This is a randomized clinical trial (RCT) of 2 parallel groups (ratio 1:1) that  will be carried out in the Teaching Care Unit (UDA) of the Faculty of Health Sciences of the  University of Malaga (UMA). The study protocol conforms to the items of the Recommendations  for Interventional Trials (SPIRIT) and the RCT will conform to the Consolidated Standards for  Reporting Testing (CONSORT).  Recruitment: Patients will be recruited by invitation to participate via email to the  university community, as well as contact with Family Medicine professionals for the referral  of patients who meet the inclusion criteria will be invited to participate in the RCT.  Doctors involved in the recruitment process will receive a clinical session to ensure that  the selection process is carried out according to the inclusion criteria and that  participants do not meet the exclusion criteria.  Patients will receive oral information and a written document (Patient Information Sheet). If  the patient is interested in participating in the study, after signing the informed consent,  he will be summoned to be evaluated by an external evaluator who will perform the initial  assessment. The patient will also receive a revocation sheet in case they decide to leave the  study at any time. After the initial assessment, participants will be randomly assigned to  one of two study groups (experimental or control).  Randomization After the initial evaluation, each patient will be assigned an alphanumeric  code for the identification of each subject, thus respecting their anonymity. To perform the  randomization procedure, the principal investigator (PI) will receive a list of the  alphanumeric codes of the participants and perform a random assignment using the SPSS  statistical package.  Blinding An independent biostatistician will perform the statistical analysis without knowing  the treatment performed by each group. Participants and physiotherapists performing the  intervention cannot be blinded, but the physiotherapists performing the intervention are not  involved in the patient assessment process.  Similarly, the evaluator will also be unaware of the participant assignment group in order to  establish blinding of the evaluator.  Intervention  -  Control group: The control group will perform a VRi placebo intervention with the game  "Tsuro", which consists of a puzzle-based strategy game where the patient will have to  solve a maze by placing pieces. This intervention will attempt to assess the influence  of the immersive context and the playful component compared to the intervention group.  This treatment will last 3 sessions / week of 15 minutes, therefore taking a total  duration of two weeks of treatment with a total of 6 sessions.  -  Intervention group: You will perform active treatment using Virtual Reality software  based on pain education and gamified exercise for gradual exposure to shoulder movement.  The game involves visual stimuli and shoulder movement exercises in the shoulder flexion  and abduction ranges in real time using immersive glasses located on the head and two  controls on both hands. Patients will inhabit an avatar from an egocentric perspective.  The intervention will last 3 sessions / week of 15 minutes, therefore carrying a total  duration of two weeks of treatment. Within the intervention will consist of a pill of  education in pain neuroscience (PNE) of 1 minute duration, followed by an exposure level that  will last 2:30 minutes where a progression will be made in number of ranges of motion and  speed. Each session will consist of 2 intervention blocks (PNE + Gradual Exposure). The  content of the PNE educational pills have been selected according to the objective of the  study.  -  Pain as an alarm system  -  Protectometer  -  Persistent pain, characteristics  -  Persistent pain Why?  -  Persistent pain, neuroplasticity  -  Sensory and interpretation component  -  The complexity of the body  -  Threshold depends on context  -  PD, Sensitivity  -  Imaging tests  -  Negative effects of imaging tests  -  The solution is in you  Data collection procedure  The study protocol will be recorded in Clinicaltrials.gov, prior to data collection.  Who will collect the data: A physiotherapist with experience in managing people with  persistent musculoskeletal shoulder pain and training by the research team will be  responsible for data collection.  When data will be collected: Pain variables during movement and range of motion and grip  strength will be measured before the intervention and after the intervention in each  treatment session Demographic variables will be collected at the beginning of the study.  Finally, the variables of Self-efficacy, Kinesiophobia, Fear of pain and disability will be  collected at the beginning of the intervention and at the end of the intervention after 1  week of treatment.  How the data will be collected: all variables will be measured with the self-reported  questionnaires discussed in the table above, since they are validated and reliable measures  to assess these factors.  Data analysis  All data will be evaluated to check the normality of its distribution. The numerical  variables will be summarized with means and standard deviations and the categorical ones with  percentages. Numerical variables that show a distribution far removed from normal will be  transformed to obtain distributions close to normal, or otherwise, they will be summarized by  using percentiles. For the graphical representation of the distribution of the numerical  variables in each treatment group, we will use box and whisker graphs. To represent  categorical variables, pie charts will be used.  In order to test the equality of means for numerical variables, we will apply Student's T if  the distributions are not far from normal. Otherwise, we will calculate the  Wilcoxon-Mann-Whitney statistics. Depending on the observed response to treatment in  numerical variables or the observed change in them, we will construct several definitions of  success/failure for the treatment outcome in individuals.  We will adjust logistic regression models to predict treatment success. These models will  include those variables that show a statistically significant relationship with the  corresponding outcome variables in the univariate analysis. It shall be considered as  statistically significant p-values below 0,05. All models will be adjusted for age, gender,  pain intensity and pain duration. These variables will be used as adjustment variables due to  their importance as factors associated with chronic pain The analysis of the data will be  carried out through the use of statistical software Inclusion Criteria:  -  People from 18 to 65 years old  -  Shoulder pain of at least three months of evolution located in the proximal  anterolateral region of the shoulder  -  Presenting shoulder pain during movements with a history of traumatic or insidious  onset  -  Agree to participate in the study and sign the informed consent Exclusion Criteria:  -  Shoulder pain resulting from cervical spine dysfunction  -  Cognitive deficits  -  Uso of medications for pain control in the previous 24 hours  -  A history of neurological or psychiatric disorders  -  Adhesive capsulitis syndrome (limited passive range of motion of the shoulder:  external rotation < 30°; elevation < 150°)  -  Patients with shoulder instability  -  Previous surgery of the shoulder

This study will be conducted using a randomized, controlled, crossover design with three  treatments. The purpose of the study is to determine the effects of diabetes-specific formula  on glycemic control in individuals with type 2 diabetes. All study participants will be asked to attend a test session where their glycemic,  insulinemic and satiety response to a test meal will be measured, followed by a seven-day  washout period where they will not receive or consume any study meal during this period. This  cycle will be repeated until all participants complete three test sessions. Inclusion Criteria:  1. Age ≥ 21 and ≤ 65 years.  2. Participant has type 2 diabetes as evidenced by use of oral antihyperglycemic  medication(s), except for DPP-4 inhibitors, with constant dose for at least two months  prior to screening and baseline visit. Participant is able to maintain medication  number, type and dose throughout the duration of study.  3. Participant with a BMI > 18.5 and ≤ 35.0 kg/m2.  4. Participant is weight stable (has maintained current body weight within 3 kg) for the  two months prior to the screening visit.  5. Male or a non-pregnant, non-lactating female, at least 6 weeks postpartum prior to  screening visit. A urine pregnancy test is required for all female subjects unless she  is not of childbearing potential, defined as postmenopausal for at least one year  prior to screening visit or surgically sterile (bilateral tubal ligation, bilateral  oophorectomy, or hysterectomy). If female is of childbearing potential, is practicing  one of the following methods of birth control (and will continue through the duration  of the study):  -  Condoms, sponge, diaphragm or intrauterine device;  -  Oral or parenteral contraceptives for 3 months prior to screening visit;  -  Vasectomized partner;  -  Total abstinence from sexual intercourse.  6. If the participant is on a chronic medication such as an anti-hypertensive,  lipid-lowering, thyroid medication or hormone therapy, the dosage was constant for at  least two months prior to screening and baseline visit. Participant is able to  maintain medication number, type and dose throughout the duration of study.  7. Participant is willing to follow protocol as described, including consumption of study  product per protocol and completing any forms needed throughout the study.  8. Participant has at least a two-week washout period between completion of a previous  research study that required ingestion of any study food or drug and their start in  the current study.  9. Participant is willing to refrain from taking non-study diabetes-specific formulas  over the entire course of the study.  10. Participant has voluntarily signed and dated an Informed Consent Form (ICF), approved  by an Independent Ethics Committee/Institutional Review Board (IEC/IRB) prior to any  participation in the study. Exclusion Criteria:  1. Participant has a screening HbA1c level <7% or ≥ 10%.  2. Participant uses exogenous insulin or GLP-1 agonists or DPP-4 inhibitors for glucose  control.  3. Participant has confirmed type 1 diabetes and/or had history of diabetic ketoacidosis.  4. Participant has current infection (requiring medication), inpatient surgery or  received systemic corticosteroid treatment (with the exception of inhaled (includes  nasal), topical, and ophthalmic steroids) in the last 3 months; or received  antibiotics in the last 3 weeks.  5. Participant has active malignancy (excluding the following dermal malignancies: basal  cell carcinoma, squamous cell carcinoma, carcinoma in-situ of the cervix).  6. Participant has significant cardiovascular event within 6 months prior to study entry  or history of congestive heart failure.  7. Participant has end stage organ failure (such as end stage renal disease) or was post  organ transplant.  8. Participant has a history of renal disease or severe gastroparesis.  9. Participant has current hepatic disease.  10. Participant has had bariatric surgery including gastric balloon; history of  gastrointestinal disease (e.g., Crohn's, colitis, celiac) or intestinal surgery that  can interfere with consumption or digestion or absorption of study product.  11. Participant has a chronic, contagious, infectious disease, such as active  tuberculosis, Hepatitis A, B or C, or HIV.  12. Participant has eating disorder, severe dementia or delirium, history of significant  neurological or psychiatric disorder, alcoholism, substance abuse or other conditions  that may interfere with study product consumption or compliance with study protocol  procedures in the opinion of the principal investigator or study physician.  13. Participant is taking any herbals, dietary supplements, or medications, other than  allowed anti-hyperglycemic medications, during the past four weeks prior to screening  visit that could profoundly affect (in the opinion of the principal investigator)  blood glucose or appetite (examples include orlistat, contrive, qsymia, belviq,  incretins, cannabis).  14. Participant uses diabetes-specific formula(s), (e.g. Glucerna, Nestle Nutren Diabetes,  Kalbe Diabetasol, Appeton Nutrition Wellness 60+ Diabetic, ForSure, Penta Sure DM,  Resurge DM, Diben, Diasip, etc.) defined as more than one eating occasion per week in  the last three months.  15. Participant has clotting or bleeding disorders. The use of Plavix® or a similar  anticoagulant drug with no reported difficulty during blood draws is allowed and  participant is able to maintain medication number, type and dose throughout the  duration of study.  16. Participant participates in another study that has not been approved as a concomitant  study by AN.  17. Participant has an allergy or intolerance to any ingredient in the study product, as  reported by the participant.

The experimental nature of this study will provide the empirical data in analyzing the  effectiveness of gratitude exercises which later can be adapted in stress reduction programs  at school level. This research will focus on the school related positive life experiences for  example thinking about a teacher/mentor kindness and contribution in their lives, then write  a letter that describes their gratitude & letter will be delivered to that person indirectly.  This may help in focusing on the positive aspects of school life. This modification will  serve as testing this new model for assessing the combined effect of gratitude interventions. Academic stress is an inevitable part of students' lives with long-term negative consequences  on physical health, mental well-being, and social relations. In Asian cultures, expectations  of parents and teachers are additional components of academic stress which have not been  addressed in different stress management programs. Therefore, the present research addresses  these contributory stress factors by using gratitude interventions in Pakistani high schools.  The study employs Broaden and Build Theory and Cognitive Appraisal Theory in formulating the  intervention model and variables being tested through pretest-posttest experimental research  design with a control group. A total of 102 high school students from two genders segregated  schools of Rawalpindi city, Pakistan, served as the participants. They were randomly assigned  into experimental and control groups, with 51 participants in each group. There were 41 boys  and 61 girls with a mean age of 15.71+ 0.92 years. The measures included Academic  Expectations Stress Inventory (AESI), Inventory of High-School Students' Recent Life  Experiences (IHSSRLE), Modified Differential Emotions Scale (mDES), Gratitude Questionnaire-6  (GQ-6) and Gratitude Adjective Checklist (GAC). Three gratitude interventions, including  Count your Blessings, Gratitude Letters and Loving-Kindness Meditation, were modified to  focus on school-related experiences. The model consisted of nine sessions applied in schools  for four weeks with 30-40 minutes each day. The research protocol and intervention model were  adapted into Urdu for better understanding among participants. The data were analyzed through  descriptive and inferential statistics (frequency, percentage, mean, SD, paired sample  t-test, independent sample t-test, multivariate analysis of variance and effect size). Inclusion Criteria:  -  High School Students  -  Studying in same school for at least last six months  -  within 14-17 years of age  -  not having severe physical health issue or going under treatment for chronic illness Exclusion Criteria:  -  not able to understand Urdu language  -  above 17 years of age or below 14 years  -  recently enrolled in the particular school

In this study, the investigators will prospectively collect, analyze and integrate  information regarding vaginal microbiome composition and HPV presence in women with cervical  pathologies (high-grade CIN and CC) and controls, to construct a large dataset from patients  with pre-cancerous cervical lesions and healthy women, to evaluate the personalized  contribution of the vaginal microbiome to the CIN-CC sequence. Infection with high-risk Human Papillomavirus (HPV) genotypes constitutes a well-recognized  risk factor for cervical-carcinoma (CC). High-risk HPV features 10-15% persistence rate,  consequently driving precancerous cervical-intraepithelial-neoplasia (CIN) and subsequent  progression to CC. Multiple factors are believed to play permissive roles in the progression  of CIN/CC , yet a molecular mechanism driving carcinogenesis across the CIN-CC continuum  following persistent HPV infection remains elusive. The vaginal microbiome may play a role in  the development of CIN-CC carcinogenesis, by modulation of host-immune-response and  alteration of cervical microenvironment to become tumor-permissive. While suggested vaginal  microbiome contributions include induction of altered epithelial cell adhesion and  downregulation of DNA damage responses, no clear mechanism has been proven to date. The loss  of Lactobacillus genus dominancy, and the switch to dysbiotic, high-diversity, high-pH,  Bacterial Vaginosis (BV) is thought to play a key-role in HPV infection, persistence and  carcinogenesis.  the investigators hypothesize that specific vaginal microorganisms may promote HPV  persistence, chronic inflammation and progression through the CIN-CC sequence, and the  elimination of harmful bacteria or supplementation of beneficial microbes, could possibly  reverse HPV persistency and inhibit CIN-CC progression.  The current study consists of recruitment of a human cohort of healthy, CIN and CC patients  including vaginal samples and comprehensive metadata collection. The investigators plan to  conduct an in-depth characterization of vaginal microbiome to identify associations with HPV,  CIN and CC. Inclusion Criteria:  -  Age 25-70  -  Attended the clinic for a Pap smear or colposcopy Exclusion Criteria:  -  Patient does not approve sample collection  -  Usage of antibiotics in the month prior to clinic visit  -  Usage of any vaginal preparation or medication in the week prior to sample collection  (anti-fungal, spermicides, lubricant etc.)  -  Menstruation  -  Pregnancy

Knee pain is one of the most usual pain that commonly affects people especially in the late  age. It can be caused by osteoarthritis, poor posture or sitting position, bad bending or  improper lifting. It is usually not caused by a serious illness. It is the most common cause  of disability. To compare the long term effects of Mulligan Mobilization with Movement versus  Macquarie Injury Management Group on pain and function of knee osteoarthritis. It was a randomized clinical trial conducted in Revival Physiotherapy Center, Lahore. A  convenient sample of 26 diagnosed patients with osteoarthritis was included in the study.  Subjects were randomly distributed in to two groups with use of flip coin method Group of  randomization. Group 1 patients got MIMG with routine physical therapy and Group 2 got MWM  with routine physical therapy. Visual analogue Scale (VAS),Non modified WOMAC were used to  assess all patients before and after 4 weeks of intervention. Statistical analysis was  computed by SPSS 20.0. Inclusion Criteria:  -  ACR criteria for knee will be over age 50  -  less than 30 minutes of morning stiffness,  -  Crepitus on active motion,  -  Tenderness  -  Enlargement  -  No palpable warmth of synovium.  -  Osteoarthritis grade 1 and 2 by Kelly-green and Lawrence method. Exclusion Criteria:  -  Any surgical procedure done in past 6 months and metal implants in lower extremity.  -  Any infection and neoplastic disorder.  -  Post traumatic knee stiffness.  -  Secondary knee O A peripheral vascular disease

We will investigate the beneficial and harmful effects of combining dexamethasone (12 mg) and  dexmedetomidine (1mcg/kg) as adjuncts to popliteal and saphenous nerve blocks in patients  undergoing surgery of their foot or ankle. Patients scheduled for osseous surgery of their foot or ankle with general anaesthesia and  popliteal+saphenous nerve blocks will be randomised to dexamethasone (12 mg) versus  dexamethasone (12mg) + dexmedetomidine (1mcg/kg) versus placebo in order to assess the  beneficial and harmful effects of combining dexamethasone and dexmedetomidine as adjuncts to  peripheral nerve blocks. Patients will be centrally allocated according to a  computer-generated random allocation sequence with random, permuted blocks. The trial  medication will be prepared by an un-masked nurse not otherwise involved in the trial.  Participants, personnel, care givers, investigators, outcome assessors, and data analysts  will be masked to treatment allocation. Inclusion Criteria:  -  Scheduled for unilateral osseous surgery of the ankle or foot  -  General anaesthesia with both a popliteal and a saphenous nerve block for  postoperative analgesia  -  Age of 18 or above  -  American Society of Anaesthesiologists Physical Status Score of 1 to 3  -  Body Mass Index of 18 to 40, but a minimum weight of 50 kg.  -  For fertile women, negative urine humane choriongonadotropine test and use of safe  anti-conception  -  Ability to understand the trial protocol, risks, benefits, and provide signed informed  consent Exclusion Criteria:  -  Inability to read and understand Danish  -  Uncooperativeness (as judged by investigators)  -  Participation in another trial involving medication  -  Allergy to study medication  -  Daily use of opioids above 30 mg/day morphine (or equivalents)  -  Daily use of corticosteroids of more than 5 mg prednisolone equivalents within the  past one month  -  Neurological or musculoskeletal disease making block performance impossible (as judged  by investigators)  -  Dysregulated diabetes (as judged by investigators)  -  Dysregulated anticoagulants (as judged by investigators)  -  History of drug or alcohol abuse  -  Glaucoma  -  Contraindications for paracetamol or opioids  -  Contraindications to general anaesthesia  -  Other concomitant conditions needing surgery  -  Other concomitant traumatic injuries

The sample will comprise 12 adult women (aged 18 to 40 years) and overweight (BMI> 24.9 kg /  m² and <30.0 kg / m²). The experimental design will consist of four assessments. In the first  assessments a structured questionnaire will be applied to obtain health and food consumption  data, in addition to evaluate anthropometric (weight, height, waist and hip circumference),  and collection of blood. In addition, an ultrasound examination, digital photography and  biopsy of the subcutaneous WAT, of the abdominal region, will be performed. After 30 day  subjects will undergo CoolSculpting treatment(s) in an outpatient clinical setting. The  treatment is comprised of timed segments of cooling and heating; a vacuum treatment may  include an optional massage. Treatments will be administered according to the User Manual  CoolSculpting System. The volunteers will return for the biopsy of the subcutaneous WAT, from  the abdominal region, in 3 days after the procedure. In 4º assessment, 60 days after  cryolipolysis, all evaluations performed in the first assessment will be repeated and to  evaluate overall patient satisfaction for non-invasive fat reduction in CoolSculpting  subjects. This is a longitudinal, non-randomized clinical trial to assess the biology of AT after the  use of cryolipolysis. The study will be developed at "Clinica Dra Ligia Colucci" in  partnership with the Federal University of Minas Gerais (UFMG). The project will be submitted  for evaluation by the Research Ethics Committee (COEP / UFMG). All participants must sign the  informed consent form (ICF), before the study begins.  The experimental design will consist of five stages. Initially, women will be public  recruitment. Through telephone contact, the inclusion and exclusion criteria will be  verified, and volunteers who meet the criteria will be invited to attend the clinic for the  first stage of the study. The presentation of the research, will be carried out 7 days before  the beginning of the treatment, will consist of presenting the project to the volunteers,  explaining all the risks and benefits related to the study and request the signature of the  ICF. After 7 days, the volunteers must return to the clinic, then start the study. In the  initial evaluation, an anamnesis of the volunteers will be carried out with a standardized  form, including socioeconomic and clinical data, data on the use of medications, alcohol  consumption, physical activity and food consumption. In addition, anthropometric assessments  will be performed where weight, height, waist, abdominal and hip circumference will be  measured. Ultrasonography will also be performed; the abdominal region will be photographed  and blood will be collected to measure lipolytic and inflammatory markers and a biopsy of the  subcutaneous WAT in the lower abdomen via umbilical scar. In addition, questionnaires will be  applied to check the volunteers' satisfaction with the treatment. After 30 days, the  volunteers must return to the clinic for time 0 (T0), where anthropometric assessments will  be repeated as control variables. Ultrasound and blood collection will also be performed.  Then the volunteers will be submitted to cryolipolysis in the abdominal region by the  Coolsculpting® system. After 3 days of performing the Coolsculpting® procedure, the  volunteers must return to the clinic for time 3 (T3), to perform a new biopsy of the  subcutaneous WAT in the lower abdomen via the umbilical scar. After 60 days of the  cryolipolysis, the volunteers must return to the clinic for the time 60 (T60), where all the  evaluations of the initial evaluation will be carried out again and a personal satisfaction  questionnaire will be applied in relation to the result of the procedure. Therefore, the  study will total 97 days of monitoring of women, who will be instructed to maintain healthy  lifestyle habits, according to the conventional lifestyle of each one of them. The data,  images and biological materials (blood and adipose tissue biopsy) collected in the research  will be filed with the researcher responsible for a period of 5 (five) years at the  Experimental Nutrition Laboratory, room 315, of the UFMG School of Nursing and after that  time will be destroyed. In case of occurrence of paradoxical adipose hyperplasia after the  procedure, a case study of the possible affected patients will be carried out. Inclusion Criteria:  -  Subject has clearly visible fat in the flanks and/or abdomen, which in the  investigator's opinion, may benefit from the treatment.  Subject has not had weight change fluctuations exceeding 4.5 kg (or 5% of body weight) in  the preceding month.  Subject has a BMI of 24.9 to 30. A BMI is defined as weight in kilograms divided by height  in meters squared (kg/m2).  Subject agrees to maintain weight (ie, within 5% of body weight) by not making any changes  in diet or exercise routine during the course of the study.  Subject agrees to have photographs taken of the treatment area(s) during the scheduled time  periods. Exclusion Criteria:  -  Subject has had liposuction, or another surgical procedure(s) or mesotherapy in area  of intended treatment.  Subject has had a non-invasive fat reduction and/or body contouring procedure in the  area(s) of intended treatment within the past 12 months.  Subject needs to administer, or has a known history of subcutaneous injections into the  area(s) of intended treatment (eg, cortisone, heparin, insulin) within the past 6 months.  Subject is pregnant or intending to become pregnant. Subject is lactating or has been  lactating in the past 6-9 months. Subject is unable or unwilling to comply with study  requirements. Subject is currently enrolled in a clinical study of any unapproved  investigational device, investigational product or any other type of medical research  judged not to be scientifically or medically compatible with this study.  Subject has an active implanted device such as a pacemaker, defibrillator, or drug delivery  system or any other metal containing implant.  Subject with known history of cryoglobulinemia, cold agglutinin disease, or paroxysmal cold  hemoglobinuria.  Subject with known sensitivity to cold or has any condition with a known response to cold  exposure that limits blood flow to the skin such as cold urticaria or Raynaud's disease, or  Chilblains (pernio).  Subject with known sensitivity or allergy to fructose, glycerin, isopropyl alcohol, or  propylene glycol.  Subject with impaired peripheral circulation in the area to be treated Subject with  neuropathic disorders such as post-herpetic neuralgia or diabetic neuropathy.  Subject with impaired skin sensation. Subject with open or infected wounds. Subject with  bleeding disorders, or concomitant use of blood thinners, or is taking any medication that  in the investigator's opinion may increase the subject's risk of bruising.  Subject with recent surgery or scar tissue in the area to be treated. Subject has history  of hernia in or adjacent to the treatment area(s) site. Subject with skin conditions such  as eczema, dermatitis, or rashes in the area to be treated.  Subject has any dermatological conditions, such as moderate to excessive skin laxity, or  scars in the location of the treatment sites that may interfere with the treatment or  evaluation (stretch marks is not an exclusion).  Subject is taking or has taken diet pills or supplements within the past 6 months.  Any other condition or laboratory value that would, in the professional opinion of the  investigator, potentially affect the subject's response or the integrity of the data or  would pose an unacceptable risk to the subject.  Subject diagnosed with fibrosis.

The goal of this study is to determine the effectiveness of interactive feedback from a  wearable device that senses hand function, the Manumeter, in improving upper extremity  function in a pilot, randomized controlled trial with chronic stroke patients In this randomized controlled trial, the investigators will compare two groups of chronic  stroke participants Group 1 of study participants will use the Manumeter with interactive  functions to monitor and motivate upper extremity functional activity. Group 2 of study  participants will use the Manumeter but receive no feedback and will be given the current  standard-of-care, a booklet describing a home exercise program for increasing upper extremity  exercise. The investigators hypothesize that study participants who interactively monitor  functional activity with the Manumeter will improve their upper extremity function  significantly more. Inclusion Criteria:  -  18 to 80 years of age  -  Experienced one or multiple strokes at least six months previously  -  Upper Extremity Fugl-Meyer Score < 60 out of 66  -  Absence of moderate to severe upper limb pain (< 3 on the a 10 point visual-analog  pain scale)  -  Ability to understand the instructions to operate the device Exclusion Criteria:  -  80 years of age and above  -  Implanted pacemaker  -  moderate to severe pain in affected arm  -  severe tone in affected arm as measured on a standard clinical scale  -  language problem that would prevent from properly understanding instructions  -  currently pregnant  -  difficulty in understanding or complying with the instructions given by the  experimenter  -  inability to perform the experimental task that will be studied

The study will evaluate the performance, clinical benefits and safety of the Persona Revision  Knee System in patients who have received primary or revision total knee arthroplasty (TKA)  treatment. This will be done using a multicenter, single-arm, consecutive series,  retrospective cohort study with prospective follow-up. Under study are the Persona® Revision Knee System (K181947 and K191625) implants and  instrumentation, and any compatible devices being used in conjunction according to the  Instructions for Use. This will be accomplished by retrospectively identifying patients who  underwent primary or revision TKA with this system and inviting them to participate in  prospective data collection at 1 and 2-years postoperative follow-up. As the device was not  available for commercial use until late 2019, the retrospective portion will involve those  activities that occurred per standard of care for participants.  The primary endpoint for this study will be performance assessed by improvement in the 1989  Knee Society Clinical Rating System (KS) objective knee score (KS-KS) from baseline to 2  years (as evaluated using the overall group mean showing at least the Minimal Clinically  Important Difference (MCID) of 5.4 points).  A maximum of 20 sites will contribute to this study. There will be a maximum of 380 patients  enrolled in the study. Inclusion Criteria:  1. Male or female of at least 18 years of age at the time of screening.  2. Signed an institutional review board approved informed consent.  3. Willingness and ability to comply with the study procedures and visit schedules and  ability to understand and follow oral and written post-operative care instructions.  4. Previous medical diagnosis/ history of at least one of the following conditions  requiring treatment using the Persona Revision Knee System within a pre-specified  study variant configuration (cohort), in accordance with the instructions for use  (IFU):  1. Rheumatoid arthritis, osteoarthritis, traumatic arthritis or polyarthritis  2. Collagen disorders, and/or avascular necrosis of the femoral condyle  3. Post-traumatic loss of joint configuration, particularly when there is  patellofemoral erosion, dysfunction or prior patellectomy  4. Moderate valgus, varus, or flexion deformities  5. The salvage of previously failed surgical attempts or for a knee in which  satisfactory stability in flexion cannot be obtained at the time of surgery  5. A pre-operative Knee Society Knee Score (objective assessment) ≤ 80. Exclusion Criteria:  1. Presence of clinically observed active or suspected latent infection in the affected  joint at the time of procedure.  2. Previous history of infection in the affected joint that may affect the prosthetic  joint.  3. Presence of or history of local/systemic/distant focal infection that may affect or  hematogenously spread to the prosthetic joint.  4. Skeletal immaturity or insufficient bone stock on femoral or tibial surfaces which  cannot provide adequate support and/or fixation to the prosthesis.  5. Diagnosed with neuropathic arthropathy, osteoporosis, or any loss of musculature or  neuromuscular disease that compromises the affected limb.  6. Presence of a stable, painless arthrodesis in a satisfactory functional position in  the affected joint.  7. Severe instability of the affected joint secondary to the absence of collateral  ligament integrity.  8. Diagnosis of rheumatoid arthritis in conjunction with any of the following at the time  of screening:  1. An ulcer of the skin  2. History of recurrent breakdown of the skin  3. Use of steroids  9. Patient requires simultaneous bilateral knee surgery for treatment of diagnosed  condition.  10. Pregnant or women planning to become pregnant during the time they will be  participating in the study.  11. Any documented clinically significant degree of cognitive impairment or other  condition, finding, or psychiatric illness at screening which, in the opinion of the  Investigator, could compromise patient safety or interfere with the assessment of the  safety and treatment effects of the study procedure.  12. Any patient who is institutionalized, or with a known drug or alcohol dependence  currently or within the last year.

The menstrual cycle is one of the most important signs of a functioning reproductive system  in women, but sometimes this cycle is associated with signs and symptoms that cause physical  and psychological problems for women.  Considering the high prevalence of PMS among women and the complications of this syndrome on  work performance, social and interpersonal relationships and family, and its role in limiting  education, social and economic progress in society, 8 weeks of online yoga exercises given  online to female students were helpful in reducing PMS symptoms The aim was to evaluate the  efficacy and effect on inflammation parameters. The study was planned as an interventional,  single-blind, randomized controlled study. The sample size of this study was calculated based  on the latest research available on the effect of exercise on PMS (Kamalifard et al.2017). A  power analysis was performed in student PMS scores between exercise and control groups and to  expect a difference of 80% strength and α = 0.50 and 30%. 80% power (1 - ß) minimum 18  students for each group, total 36 students will be included in the sample. The menstrual cycle is one of the most important signs of a functioning reproductive system  in women, but sometimes this cycle is associated with signs and symptoms that cause physical  and psychological problems for women.  Considering the high prevalence of PMS among women and the complications of this syndrome on  work performance, social and interpersonal relationships and family, and its role in limiting  education, social and economic progress in society, 8 weeks of online yoga exercises given  online to female students were helpful in reducing PMS symptoms The aim was to evaluate the  efficacy and effect on inflammation parameters. The study was planned as an interventional,  single-blind, randomized controlled study. The sample size of this study was calculated based  on the latest research available on the effect of exercise on PMS (Kamalifard et al.2017). A  power analysis was performed in student PMS scores between exercise and control groups and to  expect a difference of 80% strength and α = 0.50 and 30%. 80% power (1 - ß) minimum 18  students for each group, total 36 students will be included in the sample.  The researcher will provide brief information about the scope of the research by interviewing  the students who meet the case selection criteria online. Verbal and written consents of the  "Informed Consent Form" will be obtained (written consents will be sent to the researcher  online). Female students who accepted to participate in the study were given the "Data  Collection Form" (see Annex: 1), "Beck Depression Inventory" (APPENDIX: 2), Visual Pain Scale  (VAS) (see APPENDIX: 3) and PMS for 3 cycles. Scale (see Annex: 4) will be applied using the  online data collection method. Students who meet the sample selection criteria will be  randomly allocated to the intervention and control group by the method of computer-assisted  randomization (www.randomizer.org). In order to ensure blindness, randomization and random  distribution of the participants to the groups will be done by a researcher and will not be  shared with other researchers. and Body Mass Index will be calculated. CRP, Procalcitonin,  sedimentation, Interleukin (IL) -2, IL-4, IL-6, IL-10, IL-12, and interferon from all  participants on the day of the highest VAS score (the day when symptoms peak) and the day  when symptoms were highest. (IFN gamma), TNF alpha and PMS scale will be taken. Students in  the intervention group will be given a total of 120 minutes out of 40 minutes, and 24  sessions of yoga for 8 weeks, 3 days a week. The researcher who will make yoga with each  student will be sent videos on the online platform, including a yoga presentation and a full  yoga session with the students after a yoga session. The students were asked to do yoga 3  times a week in accordance with the video and the researcher will be called twice a week to  get information about the process. Inclusion Criteria:  -  Being in the age range of 18-35  -  To be of reproductive age,  -  Not giving birth before, Healthy women with regular menstrual periods (those who have  bleeding between menstrual cycles for 3-8 days for 21-35 days),  -  To be an undergraduate student,  -  AcOG PMS criteria (according to ACOG diagnostic criteria; women with at least one  premenstrual syndrome and symptoms in at least three consecutive cycles) Exclusion Criteria:  -  Having a regular yoga history for 3 months before and during the workout;  -  Having a chronic disease (Endocrine, DM, Heart diseases, psychiatric illness) Oral  contraceptive use  -  To have a physical problem that prevents him from doing yoga asanas  -  Over cyst and PICOS  -  Get a score lower than 110 from the total scale score according to the PMS scale score  -  Over 10 in Beck Depression Inventory, Students with a history of gynecological surgery  were excluded from the study.

The main objective of this project is to measure the increase in aerobic physical and  metabolic capacities with a 6-month training on a rower assisted by electrostimulation of  lower limbs in a population of adults with traumatic paraplegia. Beyond the inability to walk, chronic paraplegic patients show an increase in their mortality  from cardiovascular pathologies, compared to the same age groups of the general population.  It is the hypoactivity induced by neurological impairment that is implicated in the first  place in the pathogenesis of these abnormalities. The search for training methods adapted to  these patients is justified to limit cardiovascular morbidity and mortality.  The aim of this project is to measure the increase in aerobic physical and metabolic  capacities with a 6-month training on a rower assisted by electrostimulation of lower limbs  in a population of adults with stabilized paraplegia (non-walkers), of traumatic origin.  Study is divided in two 3-month phases. The first consists on a training on a rowing machine  with solicitation of the electrostimulated lower limbs only for a period of 3 months at the  rate of 3 sessions of 30 minutes per week. The second consists on a training on a rowing  machine with solicitation of the electrostimulated lower limbs and upper for a period of 3  months at the rate of 3 sessions of 30 minutes per week. The evaluations are composed of the  measurement of maximum oxygen consumption, muscle and neurological parameters Inclusion Criteria:  -  Paraplegia with traumatic origin  -  Spinal cord injury AIS (ASIA Impairment Scale) score A and B at least 12 months old  -  Patient having given written consent  -  Patient with social security scheme  -  Ability to obtain a leg extension with a 30-minute electrostimulation program Exclusion Criteria:  -  Protected adults (person in guardianship, curators or legal protection)  -  Presence of contraindication criteria to carrying out a stress test or sustained  physical activity decided by the doctor following the person with spinal cord injury.  -  Drug treatment with cardiovascular or antidepressant effect  -  Pressure sore  -  Other associated neurological pathologies (stroke, peripheral neuropathy, myopathy,  head trauma, ...)  -  Affection of the shoulders of any etiology that could compromise the ability to use  the rower.  -  Spasticity of the lower limbs: Modified Ashworth Scale (MAS) greater than or equal to  2/4 (specifically quadriceps / Hamstrings)  -  Participation in another study

The purpose of the study is to measure high grade (3-5) toxicity of regorafenib and to  monitor the impact of treatment with regorafenib on the quality of life in older adults with  metastatic colorectal cancer. Subjects will be asked to participate in the study because they are aged 70 or older and  require treatment for colorectal cancer that has spread to other parts of the body and has  not gotten better with other treatment. Subjects will undergo some initial tests to ensure  that they meet all criteria necessary to participate in the study. Once the subject has  completed initial testing and meets eligibility criteria, the subject will begin treatment  with 120 mg of regorafenib (3 tablets) each day for 21 days (3 weeks) in a 28 day cycle (4  weeks). After the first cycle, the doctor will discuss the possibility of increasing the dose  to 160 mg (4 tablets) each day for 21 days (3 weeks) in a 28 day cycle (4 weeks) based on the  subjects health status. During the study, assessments will be performed to monitor the  subjects tolerance and response to the treatment. Regorafenib will continue as long as the  subject is tolerating the treatment and the subjects colorectal cancer is either responding  to treatment or remains stable. Inclusion Criteria:  -  Histologically confirmed colorectal adenocarcinoma  -  Measurable metastatic disease.  -  Age +/> 70  -  Progression on standard therapy, not a candidate for further chemotherapy or patient  declines other options  -  Life expectancy >/= 12 weeks  -  Able to understand and willing to sign written informed consent.  -  Laboratory requirements:  -  Total bili ≤ 1.5 x upper limit or normal  -  Alanine aminotransferase & Asparate aminotransferase ≤ 2.5 x upper limit or normal  -  Serum creatinine ≤ 1.5 x upper limit or normal  -  International normalized ratio/prothrombin time ≤ 1.5 x upper limit or normal  -  Platelet count ≥ 100,000, hemoglobin ≥ 9 g/dL  -  Absolute neutrophil count ≥ 1,500. Blood transfusion to meet the inclusion criteria  not be allowed.  -  Glomerular filtration rate ≥ 60 ml/min  -  Subjects of childbearing potential must agree to use adequate contraception beginning  at the signing informed consent form until at least 3 months after the last dose of  study drug.  -  Must be able to swallow and retain oral medications Exclusion Criteria:  -  Currently receiving other systemic therapy for metastatic colorectal cancer  -  Previous assignment to treatment during this study. Subjects permanently withdrawn  from study participation will not be allowed to re-enter study.  -  Uncontrolled hypertension despite optimal medical management  -  Active or clinically significant cardiac disease.  -  Evidence or history of bleeding diathesis or coagulopathy  -  Any hemorrhage or bleeding event ≥ grade 3 within 4 weeks.  -  Subjects with thrombotic, embolic, venous, or arterial events, such as cerebrovascular  accident, deep vein thrombosis or pulmonary embolus within 6 months of informed  consent  -  History of other active malignancy within past 2 years.  -  Patients with phaeochromocytoma  -  Known history of human immunodeficiency virus infection or current chronic/active  hepatitis B or C infection.  -  Ongoing infection > grade 2  -  Symptomatic metastatic brain or meningeal tumors  -  Presence of non-healing wound, non-healing ulcer, or bone fracture  -  Renal failure requiring hemo- or peritoneal dialysis  -  Dehydration ≥ grade 1  -  Patients with seizure disorder requiring medication  -  Persistent proteinuria ≥ grade 3 Interstitial lung disease with ongoing signs and  symptoms at the time of informed consent  -  Pleural effusion or ascites that causes respiratory compromise, grade 2 dyspnea  -  History of organ allograft including corneal transplant  -  Known or suspected allergy or hypersensitivity to the study drug  -  Any malabsorption condition  -  Any condition which makes the subject unsuitable for trial participation  -  Substance abuse, medical, psychological, or social conditions that may interfere with  the subject's participation in the study.

Recent observational data showed a marked reduction of vascular and bleeding complications by  the use of ultrasound(US)-guided femoral artery puncture to gain the vascular access and  guide the implantation of the Perclose ProGlide® vascular closure system.  We aimed to compare in a 1:1 randomized fashion the effect of US-guided femoral puncture and  Perclose ProGlide® implantation optimization vs fluoroscopy-guided puncture followed by  Perclose ProGlide/ ProStyle implantation (standard approach) during TAVR. Transfemoral approach has become the standard route for a transcatheter aortic valve  replacement (TAVR) procedure. Despite the technology improvements, vascular complications and  access-related bleeding are frequently observed after TAVR and emerge predominantly within 30  days after TAVR. Recent observational data showed a marked reduction of vascular and bleeding  complications by the use of ultrasound(US)- guided femoral artery puncture to gain the  vascular access and guide the implantation of the Perclose ProGlide® vascular closure system.  We aimed to compare in a 1:1 randomized fashion the effect of US-guided femoral puncture and  Perclose ProGlide® implantation optimization vs fluoroscopy-guided puncture followed by  Perclose ProGlide/ ProStyle implantation (standard approach) during TAVR. Inclusion Criteria:  -  Eligible Patients are male or female with severe aortic stenosis evaluated by the  Heart Team as candidate to TAVR based on the current cardiology guidelines. Exclusion Criteria:  -  Refusal to participate in the study;  -  Inability to provide written consent to the study protocol;  -  Chronic immuno-suppressant therapy;  -  Any concomitant condition which, in the opinion of the Investigator, would not allow  safe participation in the study (e.g., drug addiction, alcohol abuse,  emotional/psychological disorder);  -  Enrolment in another study that could confound the results of this study;  -  Life expectancy < 1 year;  -  Any contraindication to TAVR procedure;  -  Non transfemoral TAVR.

To evaluate safety, tolerability and pharmacokinetics of NCP 112 after single and multiple  applications on the skin of healthy male volunteers. Atopic dermatitis is presented as eczematous lesions. Some rashes, discharge, and blisters  appear at the acute stage and skin lesions of lichenification appear as the skin becomes  thick and leathery at the chronic stage. If not treated properly, a vicious cycle of  inflammation of the immune system and further damage to the skin barrier is produced. In  particular, enhanced immune reaction to external environmental stimuli plays a major role in  inducing pruritis, an essential feature of atopic dermatitis. Pruritis triggers scratching,  which in turn leads to an 'itch-scratch-itch' vicious cycle', resulting in secondary skin  changes. Therefore, it is important to break the vicious cycle, which worsens the symptoms by  means of an optimal treatment.  NCP112 is a first-in-class drug candidate, with a novel target strategy for atopic  dermatitis, different from those of the other currently available drugs; The Investigators  believe that NCP112 might show a potential as an effective therapy for atopic dermatitis in  animal models. Since the efficacy and safety have not been fully elucidated, new adverse  reactions, unidentified from the non-clinical data, could appear later. Provided that NCP112  effectively alleviates atopic dermatitis, an intractable chronic disease, it is presumed that  the expected benefits would outweigh the foreseeable risks. In the present trial, safety,  including occurrences of adverse drug reactions, was thoroughly observed.  This trial was designed as a single-center, block-randomized, double-blind,  placebo-controlled, single and multiple dose-ascending trial in which subjects were allocated  to either topical application of NCP112 or placebo (vehicle).  The purpose of the present trial was to primarily access the safety of NCP112, the test drug  of the trial, in healthy male adults prior to administer the test drug to the real patients  with atopic dermatitis, the proposed indication. Inclusion Criteria:  1. A Subject who received and fully understood detailed explanations about the present  clinical trial, and whose written consent to participate in the trial and adhere to  the precautions was voluntarily obtained before any screening procedures  2. A healthy Korean male adult of age 19 to 55 years of age, inclusive, on the day of  signing the informed consent form  3. A Subject who did not have any clinically significant abnormalities observed in  physical examination, clinical laboratory tests, electrocardiography, and medical  history at the investigator's discretion during the screening  4. A Subject who was able to communicate in Korean with the investigator and comply with  the requirements of the protocol as judged by the investigator Exclusion Criteria:  1. A subject who had a body mass index (BMI) outside the 18.0 ~ 27.0 kg/m² at screening.  2. A subject who had a systolic blood pressure outside the 90 ~ 140 mmHg at screening; or  A subject who had a diastolic blood pressure outside the 60 ~ 90 mmHg at screening  3. QTc interval exceeding 450 ms on a 12-lead electrocardiogram at screening  4. A subject who did not meet the following criteria as to the clinical laboratory tests  at screening  -  ALT, AST ≤ upper normal level (ULN)x 2.0  -  Total bilirubin, Serum Creatinine ≤ upper normal level (ULN)x 1.5  -  eGFR ≥ 60 mL/min/1.73m²  5. A subject who has a history of alcohol or drug abuse; or has a positive test result  for drug/alcohol abuse at screening  6. At the discretion of the investigator, the condition for the cutaneous application of  the IP is not suitable for assessment due to the following reasons  -  Dermatologic diseases  -  Damaged skin area to be assessed not suitable for assessment due to sun burn,  excessive tanning, uneven skin tone, tattoo, scar, excessive body hair or  freckles  7. A subject who has a known history of any allergic diseases such as atopic/allergic  diseases (asthma, urticaria, eczematous dermatitis) and food allergy; or eczema  8. A subject who has a known history of allergy or hypersensitivity to any component of  the formulation of the IP or peptide drug  9. A subject who has taken any medicine (prescription and non-prescription drug, oriental  herbal medicine, health supplementary food, nutritional Supplements) within 2 weeks of  the IP dosing  10. A subject who has participated in any clinical trial and taken any IP within 6 months  of the IP dosing

The investigators want to explore the relationship between different configurations of  hypertension and the incidence of cardiovascular events by the guidelines reference range and  EMINCA recommended reference range. Then the investigators want to enroll twenty research  centers and 2200 hypertensions were planned to be collected and followed up in the 12th,  24th, 36th and 48th months after being enrolled in this study. Physical examination, ECG  examination, laboratory examination, echocardiography and carotid ultrasound should be taken  when baseline and follow-up. Echocardiographic measurement parameters were analyzed and the  relationship between the echocardiographic measurement parameters and cardiovascular events  and prognosis of hypertension. Different configurations of hypertension are important risk factor for the morbidity and  mortality of cardiovascular and cerebrovascular diseases in China. Studies have shown that  left ventricular hypertrophy (LVH) and left atrial enlargement caused by hypertension are  independent risk factors for cardiovascular events. The LVM and LAV derived from the normal  value data of Chinese healthy adults have been reported to be different from the recommended  reference values in guidelines, and the distribution characteristics of hypertension  remodeling are also different. However, the characteristics and outcomes of cardiac  remodeling in Chinese hypertensive population and whether this difference in configuration  has an impact on the treatment, prognosis and cardiovascular events of hypertensive  population are still needed to be explored.  This study was to observe the relationship between blood pressure and cardiovascular  remodeling evaluated by different standards in hypertensive population, and compare the  relationship between different cardiac configurations and cardiovascular events in Chinese  hypertensive population.  Twenty research centers and 2200 hypertensions were planned to be collected and followed up  in the 12th, 24th, 36th and 48th months after being enrolled in this study. Physical  examination, ECG examination, laboratory examination, echocardiography and carotid ultrasound  should be taken when baseline and follow-up.  Echocardiographic measurement parameters including M-mode and two-dimensional ultrasonic  parameters; doppler ultrasound parameters; relevant parameters of two-dimensional speckle  tracking, myocardial work parameters; the left ventricular remodeling parameters (LVM and  RWT); cardiac morphological changes; three-dimensional ultrasound parameters were analyzed  and the relationship between the echocardiographic measurement parameters and cardiovascular  events and prognosis of hypertension. Inclusion Criteria:  1. Age 30-75 years old;  2. No antihypertensive drugs were used and three blood pressure measurements were  conducted on different days, with systolic blood pressure ≥ 140 mmHg (1 mmHg=0.133  kPa) and/or diastolic blood pressure ≥ 90 mmHg; or have a history of hypertension and  are using antihypertensive drugs, even if the blood pressure is lower than 140/90  mmHg;  3. Left ventricular ejection fraction was normal (LVEF ≥ 0.5).  4. All patients agreed to participate in the experiment and signed the informed consent  form. Exclusion Criteria:  1. Secondary hypertension caused by renal parenchymal diseases, renal vascular diseases,  coarctation of aorta and endocrine system diseases;  2. Severe cardiovascular and cerebrovascular diseases; heart valve disease; persistent  atrial fibrillation and severe arrhythmia; previously undergone cardiovascular disease  surgery;  3. Abnormal liver function; abnormal renal function and diabetes;  4. Pregnant or breastfeeding women;  5. Expected survival time due to non-cardiovascular disease<4 years;  6. Patients with poor echocardiographic image quality.

The purpose of this study is to innovatively design and develop computerized dual-task  balance training modules and home modules, and conduct proactive clinical verification to  focus on the effectiveness of balance control and gait stabilization strategies. It is  expected that in addition to the development of the training module, a proactive study will  be conducted at the same time. During the period from the fourth quarter of the first year to  the second year, there will be 25 patients in the experimental group and 25 patients in the  control group. A total of 50 patients will undergo preliminary efficacy analysis. After mild traumatic brain injury (mTBI), patients often complain of dizziness, balance  disturbances, and gait instability. On average, dizziness accounts for about 23 to 81%, and  dizziness symptoms persist from 1.2% 6 months after the injury. Between 32.5% in 5 years. In  the past, in the process of neuron regeneration and repair after mild traumatic brain injury,  it was found that vestibular function and biomarkers may be related to balance restoration  and treatment. It is necessary to conduct further research to explain its potential mechanism  and clinical significance. In addition, balance training after mTBI can accelerate dizziness  recovery, balance control and gait stability, but the effect lasts for a limited time. The  development of a dual-task balance training module can extend the recovery time, this project  needs to be discussed in depth. This project mainly explores the influence of balance control  and gait strategies after mTBI, linking vestibular function and biomarkers; innovative design  and development of computerized dual-task balance training and home modules; combined with  computerized dual-task balance training modules can accelerate the recovery of dizziness,  balance control and gait stability after injury. Inclusion Criteria:  -  Age: 20-80 years old.  -  Patients with mild traumatic brain injury: According to the American Congress of  Rehabilitation Medicine, the loss of consciousness is less than 30 minutes, the coma  index is 13-15, and the post-traumatic amnesia is less than 24 hours.  -  Healthy patients: healthy subjects without any neurological, psychiatric, or severe  musculoskeletal medical history.  -  Regardless of gender. Exclusion Criteria:  -  Mild traumatic brain injury: moderate to severe brain injury, epilepsy, history of  cardiovascular disease, lack of intelligence, neurodegenerative diseases, history of  head trauma, systemic diseases, left-handedness, and use of psychotropic drugs.  -  Healthy subjects: any neurological, psychiatric, severe musculoskeletal medical  history.

Long COVID refers to persistent symptoms after a generally mild acute COVID-19. Because the  symptoms are often complex and vary from person to person, the term post-COVID syndrome is  used synonymously. In the ICD-10 catalog, Long COVID is mapped as U09.9 as "post-COVID-19  conditions." Long COVID carries a high risk for chronic morbidity. This has serious  consequences for individuals and society, especially when manifesting in young adulthood,  adolescence, and childhood. Current data show that predominantly young women aged 30-40 years  are affected by severe Long COVID. Despite only mild acute COVID-19, 10-15% of patients still  show persistent symptoms six months later, including particularly frequently pathological  exhaustion (fatigue), exercise intolerance with symptom worsening after exertion (so-called  post-exertional malaise), neurocognitive complaints and circulatory disorders. In addition,  general symptoms such as sleep disturbances, pain, or subfebrile temperatures have been  described, as well as symptoms of all organ systems.  In children and adolescents, less prevalence data are available to date. In initial studies,  4.4% and 4.6% of children and adolescents, respectively, show persistent symptoms after four  weeks, 9.8% of 2-11 year olds and 13% of 12-16 year olds after five weeks, and 1.8% of  children and adolescents with confirmed/probable SARS-CoV-2 infection after two months.  Long COVID often results in impairment of daily life with limited ability to go to school or  to work, up to and including inability to go to school or to work. Some patients manifest  full-blown CFS, which has also been described after other viral infections, such as after  glandular fever caused by Epstein-Bar virus (EBV). Similar to post-COVID CFS, CFS after  primary EBV infection manifests predominantly in female adolescents and young adults. Whether  it is the same severe, chronic disease despite similar clinical phenotype is uncertain.  The mechanisms of pathogenesis of Long COVID and postinfectious CFS have been poorly  elucidated. Initial studies of Long COVID suggest that autoimmunity, chronic inflammation,  endothelial dysfunction, and psychosocial aspects contribute to pathogenesis. For  postinfectious CFS, a causal interplay of genetic factors, stress, and infections has also  been postulated, inducing a vicious cycle of dysregulation of the central and autonomic  nervous system, immune defense, and metabolism. Infections with the "severe acute respiratory syndrome coronavirus 2" (SARS-CoV-2) and the  resulting "coronavirus disease 2019" (COVID-19) have been observed in Germany since January  2020 and subsequently represent a risk for the development of a complex chronic disease,  which is referred to as Long COVID.  Long COVID describes the persistence of symptoms over a period of more than four weeks from  the onset of acute COVID-19. If the symptoms persist for more than twelve weeks, they are  also referred to as post-COVID syndrome according to the NICE guideline. Other causes for the  symptoms must be excluded.  Patients experience a variety of symptoms, including fatigue, exercise intolerance with  worsening of symptoms after low exertion (post-exertional malaise, PEM), brain fog, cardiac  and/or pulmonary symptoms.  Long COVID occurs in most cases after initially mild COVID-19. The age spectrum includes  mainly young adults, although it also occurs in adolescents and children. In adults,  approximately 10-15% of patients with COVID-19 Long are thought to develop COVID symptoms.  In childhood, the number is likely to be much lower. With only limited data, a prevalence of  2-10% is discussed. Among these, the risk for adolescents appears to be higher and closer to  the risk for adults than for younger children.  There appears to be a predominance of females in all age groups. Some affected individuals  manifest full-blown postinfectious chronic fatigue syndrome (CFS).  Due to the high number of cases for COVID-19 worldwide, the prevalence of Long COVID is also  expected to increase. The increase is also reflected in the inquiry statistics at our MRI  Chronic Fatigue Center for Young People (MCFC). Many affected individuals are severely  limited in their quality of life by Long COVID, and in some cases are unable to attend school  or work. Therefore, the disease represents a major health and socioeconomic problem for  society.  While progress has been made in deciphering the pathogenesis of acute COVID-19, the  mechanisms of Long COVID are poorly understood and have been poorly studied. There is  increasing evidence that alterations in the microcirculation and autonomic nervous system may  occur due to damage from the virus itself or from persistent inflammation or autoimmunologic  processes, including the emergence of autoantibodies. For postinfectious CFS, a similar  interplay of genetic factors, stress, and infections has been postulated to induce a vicious  cycle leading to dysregulation of the central and autonomic nervous systems, immune defenses,  and metabolism.  Analogous to post-infectious CFS, patients* with Long COVID present with marked fatigue and  exercise intolerance with PEM accompanied by pain, sleep disturbances, neurocognitive  manifestations, circulatory complaints, and other complex symptoms that impair daily  functioning. However, the spectrum of symptomatology in patients* with Long COVID is  currently not fully explored. The international literature on minors and very young adults  with Long COVID is scarce and largely based on patient interviews without medical visits with  appropriate differential diagnosis or seroepidemiological studies.  The MCFC of the Polyclinic for Pediatrics and Adolescent Medicine of the Klinikum rechts der  Isar, cares for children, adolescents and young adults up to 25 years of age with  post-infectious fatigue or post-infectious CFS and increasingly patients with Long COVID.  Children and adolescents with Long COVID are evaluated and cared for in the university and  polyclinic clinics for pediatric and adolescent medicine of the Charité, the University  Children's Hospital Bochum, the Carl Gustav Carus University Hospital at the Technical  University of Dresden, the University Hospital Freiburg, the University Hospital  Hamburg-Eppendorf, the Saarland University Hospital, the University Children's Hospital Jena,  the Kassel Hospital, and the University Hospital Cologne.  After a detailed differential diagnosis to exclude organic or psychological causes of the  symptoms, a structured anamnesis is taken by means of various questionnaires and the disease  of the patients is further phenotyped clinically by laboratory analyses, functional tests and  imaging during the presentation at the MCFC and the other clinics mentioned. A common data  collection in these study centers has not been established yet.  These extensive medical data from the specialized routine care should be recorded, compiled  and made available for research in a standardized, multicenter, longitudinal and, if  possible, web-based manner with the help of the proposed Munich Long COVID Registry Study  (MLC-R). Prospectively, there is the possibility of recruiting further study centers.  The digital implementation is to be carried out in cooperation with the Munich IT company  Bitcare GmbH. Their database concepts have proven themselves in the context of the  Transplantation Cohort (Tx Cohort) of the German Center for Infection Research (DZIF) or the  COVID-19 study of the MRI of the TUM (COMRI). With support from Bitcare GmbH, our research  group is currently establishing a Germany-wide ME/CFS registry.  The aim of the MLC-R is to describe the clinical picture and its course in Germany in a  clinically precise manner and, if necessary, to derive epidemiological or medical risk  factors, to record the need for care more precisely and to define subcohorts for future  treatment approaches.  Primary objective of the study:  Phenotyping of Long COVID through a transition-oriented, longitudinal collection of  epidemiological, medical and health care data in a web-based, multicenter registry study  Secondary Objectives of the study:  1. Generate epidemiologic, medical, and health care data as a basis for innovative care  concepts, political measures and public relations.  2. Define subcohorts and baseline data for clinical trials.  3. Recording the frequency of comorbidities  4. Identification of diagnostic parameters  5. Estimation of prognosis  6. Identification of treatment approaches  7. Harmonization of diagnosis  8. Harmonization of epidemiological and clinical data collection  9. Networking of dedicated treatment centers  10. Perspective improvement of care by training of new centers regarding the standardized  data collection.  11. In case of broad consent, storage of residual materials collected in the course of  routine care Inclusion Criteria:  I. Written consent of the patient or, in the case of children and adolescents, written  consent of the patient and written consent of the legal guardian.  II. condition following confirmed or highly probable SARS-CoV-2 infection:  -  Detection of SARS-CoV-2 infection by polymerase chain reaction (PCR).  -  Detection of SARS-CoV-2 infection by rapid antigen test (AST) in the context of  matching COVID-19 symptoms.  -  Clinical diagnosis of COVID-19 with the aid of typical CT findings or on the basis of  a present olfactory and gustatory disturbance.  -  History of high-risk contact with subsequent plausible COVID-19 symptomatology.  -  Detection of anti-SARS-CoV-2-N and/or -S-IgG antibodies following anamnestic plausible  COVID-19 symptomatology.  -  Future valid biomarkers  III. suspected diagnosis according to ICD-10:  -  U09.9 ! (V) Post-COVID-19 condition, unspecified.  -  U12.9 ! (V) Adverse reactions to COVID-19 vaccine use, unspecified. Exclusion Criteria:  -  Retrospectively available medical data that are not compatible with the inclusion  criteria may lead to subsequent exclusion from the study.  -  Patients whose entire clinical picture, but not individual symptoms, can be explained  by another underlying disease according to WHO.  -  Pregnancy

Study to evaluate the efficacy, safety and tolerability of ponsegromab compared to placebo in  patients with cancer, cachexia, and elevated GDF 15. A 12 week double blind study to evaluate the efficacy, safety and tolerability of ponsegromab  compared to placebo in patients with cancer, cachexia, and elevated GDF 15.  During the initial 12-week treatment period (Part A), a total of 3 doses of ponsegromab or  placebo will be administered 4 weeks apart subcutaneously. Each dose contains two injections.  Part B is an optional open-label treatment period consisting of ponsegromab administered  every 4 weeks subcutaneously for up to one year. Part B does not include placebo.  Assessments include:  -  Body weight measurements  -  Measure the impact of ponsegromab compared to placebo on physical activity.  -  Measure the impact of ponsegromab compared to placebo on appetite, nausea and fatigue  questionnaires  -  Blood samples to evaluate safety and additional endpoints including the amount of study  drug in the blood and the effects of the study drug on levels of GDF-15 Inclusion Criteria: None Exclusion Criteria: None

This is a Phase 4, multicenter, open-label study evaluating EXPAREL infiltration into the  transversus abdominis plane (TAP) after bupivacaine hydrochloride (HCl) spinal anesthesia in  subjects undergoing elective Cesarean section (C-section). There will be two groups of subjects with approximately 40 subjects per group. Prior to the  C-section, all subjects will receive single-shot spinal anesthesia (1.5 mL bupivacaine HCl  0.75% with dextrose 8.25%). Subjects in Group 1 (Standard of Care) will receive intrathecal  morphine injection (e.g., Duramorph®) 0.2 mg in conjunction with the single-shot spinal  anesthesia. No TAP block will be administered. Subjects in Group 2 (EXPAREL/TAP) will receive  a bilateral TAP infiltration with a single 20 mL dose of EXPAREL 266 mg expanded in volume  with 20 mL of normal saline for a total volume of 40 mL (20 mL infiltrated on each side of  the abdomen). Inclusion Criteria:  1. Females ≥18 years of age at screening.  2. Scheduled to undergo elective C-section (single or multiple births).  3. American Society of Anesthesiology (ASA) physical status 1, 2, or 3.  4. Able to provide informed consent, adhere to the study visit schedule, and complete all  study assessments. Exclusion Criteria:  1. History of hypersensitivity or idiosyncratic reaction to amide-type local anesthetics  or opioids.  2. Contraindication to bupivacaine, morphine, ketorolac, ibuprofen, or acetaminophen.  3. Planned concurrent surgical procedure with the exception of salpingo-oophorectomy or  tubal ligation.  4. Use of any of the following medications within the times specified before surgery:  long-acting opioid medication, non-steroidal anti-inflammatory drugs (NSAIDs), or  aspirin (except for low-dose aspirin used for cardioprotection) within 3 days, or any  opioid medication or acetaminophen within 24 hours.  5. Initiation of treatment with any of the following medications within 1 month of study  drug administration or if the medication(s) are being given to control pain: selective  serotonin reuptake inhibitors (SSRIs), selective norepinephrine reuptake inhibitors  (SNRIs), gabapentin, pregabalin (Lyrica®), or duloxetine (Cymbalta®). If a subject is  taking one of these medications for a reason other than pain control, she must be on a  stable dose for at least 1 month prior to study drug administration.  6. Clinically significant medical or psychiatric disease that, in the opinion of the  Investigator, would constitute a contraindication to participation in the study or  cause inability to comply with the study requirements.  7. History of, suspected, or known addiction to or abuse of illicit drug(s), prescription  medication(s), or alcohol within the past 2 years.  8. Received an investigational drug within 30 days prior to study drug administration,  and/or has planned administration of another investigational product or procedure  while participating in this study.  9. Previous participating in an EXPAREL study.  The subject will be withdrawn from the study if she meets the following criteria:  10. Any clinically significant event or condition uncovered during the surgery (e.g.,  excessive bleeding, acute sepsis) that might render the subject medically unstable or  complicate the subject's postsurgical course.  11. Her baby's 5-minute Apgar score is ≤7.

Temporomandibular joint disorders (TMD) , a musculoskeletal condition , includes a series of  clinical problems involving the temporomandibular joint (TMJ), the masticatory muscles, and  related structures.This study evaluates the efficacy of integrated traditional Chinese and  western medicine in the treatment of TMD. In this study, 84 patients ranging in age from 18 to 65 years with diagnoses of TMD will be  randomly divided into two groups: an experimental group (EG) who will receive the integrated  traditional Chinese and western medicine treatment group(with Low-Level Laser  Therapy+acupuncture) and a control group who will receive the only western medicine  treatment(with Low-Level Laser Therapy).Both approaches will be applied 3times a week for 3  weeks. Inclusion Criteria:  1. diagnosis of TMD according to the Diagnostic Criteria for TMD Research Diagnostic  Criteria (DC/TMD）which are manifested as joint pain during mouth opening and chewing,  mouth opening limitation (<40mm), joint clanging, masticatory creatine distension and  weakness, which affects normal eating.  2. Aged 18-65;  3. Unilaterally;  4. No any other treatment on TMD in the last 3 months; Exclusion Criteria:  1. there are tumors, joint degeneration and other serious lesions ;  2. Patients with a history of TMJ trauma or surgery,joint anatomical variation;  3. women pregnant and suckling period;  4. serious systemic diseases of bone and joint, such as rheumatoid arthritis

Urolithiasis is a common health problem worldwide affecting approximately 10% of the  population at some stage in their lives. The aim of this study is to evaluate the efficacy of  adjuvant treatment with tamsulosin for improving the stone-free rate after a single session  of extracorporeal shock wave lithotripsy (ESWL) in the treatment of radiopaque kidney stones. Urolithiasis is a common health problem worldwide affecting ∼10% of the population at some  stage in their lives. It affects approximately 5% of women and 12% of men in the United  States, and it has been suggested that the incidence is increasing. Because of its efficacy  and low morbidity, extracorporeal shock wave lithotripsy (ESWL) is an effective treatment for  kidney stones smaller than 20 mm in diameter. The objective of this therapy is to achieve an  adequate fragmentation of the calculus that allows a spontaneous expulsion of the fragments,  and finally, a stone-free state, which is not always possible.  The presence of adrenergic receptors in the ureter has suggested the involvement of the  sympathetic nervous system in its peristaltic activity. It has also been shown that alpha 1  adrenergic antagonist medications such as tamsulosin are capable of inhibiting the basal tone  and the ureteral peristalsis, causing dilation and facilitating the migration of stones. Some  authors have reported the efficacy of this type of medication for spontaneous calculus  expulsion, but there is no conclusive evidence of the adjuvant effectiveness of tamsulosin  after ESWL for stone clearance and even less among a Mexican population.  This is a single center, randomized, non-placebo-controlled study with a sample of adults  (men and women ≥18 years old) with a single radiopaque kidney stone (5-20 mm) in diameter.  Post-ESWL session, the patients will be randomly divided into two groups (the control group  and the tamsulosin group). After discharge, all patients will be instructed to drink a  minimum of 2 L water daily. The control group will receive standard treatment for analgesia  consisting of oral diclofenac (75 mg/12 h) as needed. The tamsulosin group will receive  standard treatment for analgesia plus oral tamsulosin (0.4 mg/day) for eight weeks.  Patients will attend follow-up visits every two weeks during the first month of treatment and  a final visit at the end of the second month. During each visit, vital signs will be taken, a  physical examination will be conducted, and possible adverse effects will be monitored;  additionally, a plain X-ray of the kidney, ureter, and bladder (KUB) will be taken at two and  four weeks for evaluating possible complications associated with residual fragments, as well  as an abdominal CT scan at eight weeks after the ESWL in order to determine stone-free  status.  Data will be analyzed using R Statistical Software. Descriptive statistics will be determined  for the patients' clinical characteristics, grouped by the treatment assigned (control group  and tamsulosin group) and will be compared using the Mann-Whitney U test or the chi-square  test depending on the variable type. The strength of the association between the ESWL  treatment with adjuvant tamsulosin and the stone-free rate will be evaluated by calculating  the relative risk (RR) and the number needed to treat (NNT). In all cases, an alpha=0.05 was  considered significant. Inclusion Criteria:  -  A single radiopaque kidney stone (5-20 mm) in diameter visible on CT scan of the  abdomen. Exclusion Criteria:  -  A lower calyx stone.  -  A history of spontaneous stone passage.  -  A previous failed ESWL.  -  Treatment with alpha adrenergic antagonists, calcium channel inhibitors or steroids.  -  Severe obesity (BMI≥40).  -  Pregnancy.  -  Serum creatinine ≥2 mg/dl.  -  Renal artery aneurysm and/or abdominal aorta aneurysm.  -  The presence of a ureteral stent.  -  Anatomical abnormalities or previous surgery on the upper urinary tract.  -  Bone deformities.  -  Presence of a urinary tract infection.  -  Coagulation disorders.  -  Poorly controlled hypertension.

A cross-sectional study with 829 older Mexican adults were recruited from July to September  2015, from four localities in the southern region of México. Older adults were interviewed at  their homes and a fasting blood sample was obtained for analysis of micronutrient status  (iron deficiency, vitamin B12 deficiency, folate deficiency, vitamin A deficiency and  biomarkers of inflammation). The aim of the study was to identify the main causes of anemia  in older adults with higher rates of anemia according to the recent data of the Mexican  National Health and Nutrition Survey. A survey with cross-sectional design was applied in 829 older Mexican adults, recruited  during the period July to September 2015, from four localities in the southern region of  México: including Champotón, Campeche, Mérida, and Valladolid. Older adults were interviewed  at their homes to collect nutrition, health, cognitive and dietary information.  Anthropometric measures and functionallity tests were also collected. A finger prick  capillary blood sample was collected to measure hemoblobin in situ using HemoCue. Anemia was  defined according to WHO criteria. A fasting venous blood sample was collected in 803 older  adults. Serum was separated and frozen at -20°C to measure ferritin, retinol, vitamin B12,  folate, iron, soluble transferrin receptor, C-reactive protein, interleukin 6, alpha  glycoprotein 1, hepcidin, erythropoietin in the laboratory of nutrition of the National  Institute of Public Health.  The study protocol was approved by Research, Biosecurity and Ethics Committees of the  National Institute of Public Health. Participants received a detailed explanation of the  study procedures and signed an informed consent form prior to data collection. Inclusion Criteria:  -  Community-dwelling older adults who wish to participate in the study  -  Ambulatory older adultos  -  Older adult with own decision making Exclusion Criteria:  -  Non demented  -  Non oxygen dependent  -  No disability

Iliotibial band syndrome (ITBS) is a condition frequently treated in physiotherapy. The  pathophysiology underlying this syndrome is still poorly understood. Ultrasound makes it  possible to evaluate the morphology and to quantify, with sonoelastography (SWE), the  stiffness of the iliotibial band (ITB). The objective is to determine the feasibility of a  cross-sectional study aimed at evaluating the morphometry and stiffness of the ITB in runners  with and without a diagnosis of ITBS. Socio-demographic and clinical data will be collected  and ultrasound measurements (thickness and stiffness) of the iliotibial band will be  performed in supine with the knee positioned at 2 different angles (0° and 30° flexion).  Variables such as the recruitment rate/month, the inclusion/exclusion rate, the acceptability  of the procedure will be used to characterize the feasibility. The relationship between  ultrasound measurements and clinical outcomes will be explored. The results obtained will  document feasibility issues and provide preliminary results will lay the groundwork for a  large scale study. The iliotibial band (ITB) is a complex structure in which morphometry (shape, thickness,  cross-sectional area) and viscoelastic properties remain poorly understood. While some  hypothesize that the pain originates from friction of the ITB on the femoral condyle during  knee flexion, others affirm that it is rather a compression of the ITB on the tissue  underlying fat, which is highly vascularized and innervated. Current treatments in  physiotherapy are based, in part, on the theory that stiffness in the ITB may contribute to  iliotibial band syndrome (ITBS), resulting in prescription of stretching exercises in most  rehabilitation programs. However, the plausibility of this theory remains to be demonstrated  with valid and reliable instruments. Standard-mode (B-mode) ultrasound is gaining popularity  for assessing ITB morphometry. However, these data remain to be correlated with the clinical  symptomatology. Sonoelastography (SWE), on the other hand, is used to assess tissue  stiffness. Recent studies have attempted to assess the stiffness of ITB under different  experimental conditions, but these have methodological flaws (low power) and they are carried  out in an asymptomatic population. This project is a first step to fill the gaps on ITB  morphometry and stiffness values and explore the potential association between these factors  and the clinical profile of SBIT. The primary objective is to evaluate the study the  feasibility of the protocol by documenting the variables associated with this concept.  Secondary objectives are: 1) To measure the stiffness of the distal BIT in runners with and  without ITBS; 2) Describe the morphometry of the distal BIT in the two groups of runners; 3)  Compare ITB morphometry and stiffness between the two groups of runners and 4) Investigate  the association between ultrasound variables and ITBS signs and symptoms. Inclusion Criteria:  -  Minimum of 5km/week runs  -  No pain during running (for healthy runners)  -  For ITBS group: Received an ITBS diagnosis from a doctor or a physical therapist Exclusion Criteria:  -  Concomitant affection of the hip or knee (ex: previous fracture or surgery of the  knee)

The investigators' objective is to compare the risk of treatment failure* in children  admitted to the pediatric intensive care unit (PICU) with sepsis and managed by procalcitonin  guided therapy for stopping of antibiotics ('PCT- guided therapy' group) with those managed  with standard practices based on the evidence based guidelines ('control' group).  Children with suspected or proven sepsis will be randomized to the PCT guided group or the  standard practices group and will be followed up for the outcome measures that include  treatment failure and mortality. The investigators plan to enroll 560 patients over a period  of 3 years. The investigators believe that the proposed study will provide the answer to  reducing unnecessary antibiotic usage in the PICU without causing any harm to the patient in  the form of treatment failure and/or mortality. Sepsis and bacterial infections account for more than 50% of and intensive care (ICU)  admissions and the mortality rates are as high as 40-60% reported in various studies.  Although, antibiotics are crucial in deciding outcomes in children with sepsis, however, use  of the same in non-infectious conditions has resulted in emergence of multi drug resistant  strains with high morbidity and mortality. The number of deaths from antibiotic resistant  bacteria is 700000 worldwide. A major driver for development of multi drug resistant bacteria  is antibiotic use. This indiscriminate use is much more pronounced in the ICUs with  observations from various studies indicating that 30% to 60% of antibiotics prescribed in  ICUs are unnecessary, inappropriate, or suboptimal. This is because of two major reasons a)  illness severity and b) difficulty in distinguishing true sepsis from other causes of SIRS.  In order to address these problems, researchers have tried to explore the use of novel  biomarkers to improve the accuracy, early diagnosis and stopping of antibiotic therapy of  sepsis. One such marker that is widely studied is procalcitonin (PCT). Several studies and  meta-analyses have demonstrated that PCT has excellent diagnostic accuracy for sepsis and has  a potential role in de-escalating antibiotic therapy in adult patients. Unfortunately, there  are only few observational studies and two RCT's in children published till date evaluating  the use of PCT for diagnosis of infections or de-escalation of antibiotic therapy. Moreover,  till date, there are no studies in critically ill children with sepsis who are faced with the  problem of multidrug resistant infections and have the worst outcomes. Given this background,  the investigators plan to conduct this pragmatic randomized controlled trial in children with  sepsis admitted to the Pediatric Intensive Care Unit (PICU) and already on antibiotics. The  investigators' objective is to compare the risk of treatment failure in children admitted to  the PICU with sepsis and managed by PCT guided therapy for stopping of antibiotics ('study'  group) with those managed with 'standard practices' based on the evidence based guidelines  ('control' group). Children with suspected or proven sepsis will be randomized to the PCT  guided group or the standard practices group and will be followed up for the outcome measures  that include treatment failure and mortality. The investigators' would also be comparing the  duration of antibiotic therapy between the two groups as secondary outcome measures. The  investigators plan to enroll 560 patients over a period of 3 years. The investigators believe  that the proposed study will provide the answer to reducing unnecessary antibiotic usage in  the PICU without causing any harm to the patient in the form of treatment failure and/or  mortality. The investigators also believe that in due course of time, over the years, with  restricted antibiotic usage, the issue of multi-drug resistant microbial infections in the  PICU will be addressed. Inclusion Criteria:  -  Children 2 month to 17 years admitted to the ICU and already receiving antibiotics for  suspected or proven sepsis (defined as systemic inflammatory response syndrome or SIRS  due to infection) and children who are started on antibiotics in the ICU for suspected  or proven sepsis will be included. Exclusion Criteria:  -  Children receiving antibiotics more than 24 hours before presentation  -  Children with severe immunosuppression (CD4 count of less than 200 cells/mm3,  neutropenic patients (<500 neutrophils/ml)) other than corticosteroid use  -  Children admitted for post-op observation  -  Children with an estimated length of stay less than 24 hrs  -  Children with underlying co-morbidities with possible imminent death  -  Children whose parents refuse to give an informed consent

This study will be conducted to assess the long-term safety of study drug(s) in participants  who are enrolled in Eisai-sponsored lenvatinib studies. This is an open-label extension study to roll-over eligible participants from Eisai-sponsored  lenvatinib studies. The participants may roll-over no sooner than the primary completion  dates in their parent study or after all study data for the primary outcome measure have been  collected for the parent study. The parent study is defined as the Eisai-sponsored lenvatinib  clinical study in which the participant was receiving lenvatinib either as monotherapy or as  combination therapy or was receiving any other comparator therapy. The participant can be  enrolled in the current study for the purpose of long-term safety data collection if all the  selection criteria for the current study are met. The intention is that the participant will  not be without study drug during the transition from the parent study to the rollover study. Inclusion Criteria:  It is required for all participants currently participating in other lenvatinib studies to  meet the following eligibility criteria.  -  Provide signed written informed consent for the roll-over study  -  Currently enrolled in an Eisai-sponsored lenvatinib clinical study and still receiving  at least one of the study drugs from that protocol  -  Currently deriving clinical benefit from at least one of the study drug(s) as  determined by the investigator  -  Must be able and willing to comply with the current roll-over protocol requirements  -  Continued ability to swallow and retain orally administered study drug(s)  -  Does not have any clinically significant gastrointestinal abnormalities that may alter  absorption such as malabsorption syndrome or major resection of the stomach or bowels  -  Women of childbearing potential and men with reproductive potential (if specified by  the parent study) must be willing to continue to use highly effective methods of  contraception as per local practices of standard of care during the period of the  study  -  Women of childbearing potential must have a negative serum pregnancy test at the time  of transition to the study and before continuing study drug(s) Exclusion Criteria:  -  Permanent discontinuation of all study drug(s) in the parent study due to toxicity or  disease progression and without clinical benefit  -  Receiving any prohibited medication(s) as described in the parent study  -  Any unresolved toxicity that meets the criteria for study drug(s) discontinuation or  withdrawal criteria from the parent study at the time of transition to this study  -  Uncontrolled diabetes, hypertension or other medical conditions at the time of  transition to the roll-over study that may interfere with assessment of toxicity  -  Pregnant or lactating female  -  Any serious and/or unstable pre-existing medical condition, psychiatric disorder or  other conditions at the time of transition to the roll-over study that could interfere  with participant's safety in the opinion of the investigator

By using subjective and objective measurements, the investigators monitor the change of  circadian rhythm in Intensive Care Unit (ICU) patients with acute myocardial infarction and  the effect of light therapy. The investigators include 70 patients who are admitted to coronary care unit due to coronary  artery disease, with severity between Killip I-III and age between 35-85. Participants are  randomly assigned to 2 groups, the experimental group (blue light) and the placebo group  (white light). Both groups receive light therapy or white light daily between 8am to 12pm.  The investigators use actigraphy and heart rate variation analysis, and check melatonin level  as objective measurements. The investigators use delirium scales to evaluate delirium and its  severity. The light therapy is stopped once a participant is diagnosed of delirium or  transferred, and the investigators keep following participants until discharge to evaluate  the prognosis. Inclusion Criteria:  -  Diagnosis for admission is acute myocardial infarction with severity between Killip  I-III.  -  Age is between 35-85.  -  Participants who are willing to participate in the study and sign the informed  consent. Exclusion Criteria:  -  Using sedative hypnotic drugs.  -  Blindness or severe cataract.  -  Neurological diseases such as epilepsy, brain injury, or stroke.  -  Severe mental disorder such as major depressive disorder, bipolar disorder,  schizophrenia, intellectual disability or substance use disorders.  -  Unable to communicate.  -  Participants who are unwilling to participate in the study or refuse to sign the  informed consent.  -  Participants who are not suitable to include in this study, evaluate by PI or Co-PI.

Comparison incident of urinary retention in patients with vaginal surgery of pelvic organ  prolapse, who removed urinary catheter at 24 hours versus 48 hours after surgery Vaginal surgery of pelvic organ prolapse needs to insert urinary catheter for monitoring  post-operative complication, hemodynamic status, and prevention post-operative urinary  retention. Urinary retention occur 2.4 - 43% after pelvic organ prolapse surgery, whereas  retaining urinary catheter is common cause of urinary tract infection, often  hospital-acquired infection. At Rajavithi hospital always remove urinary catheter at 48 hour  after surgery. Accordingly, appropriated time for removing urinary catheter in patients with  vaginal surgery of pelvic organ prolapse is unclear. This study aims to reduce timing for  removing urinary catheter after vaginal surgery, not increase urinary retention and  re-catheterization and reduce urinary tract infection and day of hospital stay. Inclusion Criteria:  -  Woman with pelvic organ prolapse, who undergoing vaginal surgery and agrees to  participate in this study  -  Able to understand and communicate Thai language Exclusion Criteria:  -  Woman with diabetes mellitus with HbA1C > 10.9%  -  Woman with stroke  -  Woman with urinary tract infection before surgery  -  Woman with urinary retention before surgery  -  Woman, who experienced surgery for urinary incontinence  -  Woman, with operative complication including of hemorrhagic shock (Blood pressure <  90/60 mmHg, Heart rate > 120 beats per minute, Intra-operative blood loss > or = 750  ml), urinary tract injury, bowel injury

Endodontic treatment aims to eliminate pathogenic microbes from the root canal. Hyperpure  chlorine dioxide is an endodontic irrigant. Our goal is to compare the efficacy of hyperpure  chlorine dioxide with the gold standard sodium hypochlorite in the non-surgical retreatment  of root canal treated teeth with chronic periapical lesions in a randomized clinical trial.  Forty patients having chronic apical periodontitis will randomly be chosen for the study from  the patients attending our Department of Conservative Dentistry. Endodontic treatment will be  done according to professional quidelines. The patients will randomly be divided into two  groups. In the first (control) group sodium hypochlorite, in the second group hyperpure  chlorine dioxide will be used as desinfectant. The first sample will be taken from the root  canal after removing the previous root canal obturation prior to desinfection. The second  sample will be taken one week after temporization. The samples will be evaluated by  culturing, MALDI-ToF and PCR strip test. After root canal obturation the the periapical  status will be followed by clinical evaluation and control x-rays. Endodontic treatment aims to eliminate pathogenic microbes from the root canal. This is an  almost impossible task as microbes, especially Enterococci are able to line the dentin  tubules that are nearly unaccessable to desifectants used during treatment. Hyperpure  chlorine dioxide is an endodontic irrigant. In vitro studies proved it to be a very potent  desinfectant against which bacteria do not produce resistency. It selectively binds to three  amino acids targeting bacterial cells. Due to its small molecular weight and its highly  volatile characteristics we presume that it is able to penetrate into the small dentin  tubuli. There have been many in vitro studies comparing its characteristics and efficacy, but  there have been no in vivo studies done to approve its clinical preformance so far. Our goal  is to compare the efficacy of hyperpure chlorine dioxide with the gold standard sodium  hypochlorite in the non-surgical retreatment of root canal treated teeth with chronic  periapical lesions in a randomized clinical trial. Its efficacy will be compared by  microbiological methods and by clinical and radiological evaluation. According to our  hypothesis hyperpure chlorine dioxide is more effective antimicrobial agent than the gold  standard sodium hypochlorite. The protocol for this clinical study was approved by the  Hungarian National Ethics Committee for clinical trials. Forty patients having chronic apical  periodontitis will randomly be chosen for the study from the patients attending our  Department of Conservative Dentistry. Written consent will be collected from the patients.  Only those patients will be accepted who had the root canal treatment done more than four  years ago, the tooth is asymptomatic, functionally and esthetically restorable, the coronal  restoration can be done within 3-4 weeks of the root canal obturation, who will not have  prosthetic or orthodontic treatment interfering with the radiological follow-up and have no  general medical conditions or medication influencing the healing of the periapical lesion.  Endodontic treatment will be done according to professional quidelines. After sterilizing the  tooth and its environment, a sterility test will be be done by taking samples from the top of  the restoration (S1) and from the pulp chamber (S2). The root canal obturation will be  removed mechanically and a microbiological sample will be taken from the root canal (M1).  After taking the sample from the root canal the tooth will be chemomechanically prepared. The  patients will randomly be divided into two groups. In the first (control) group sodium  hypochlorite, in the second group hyperpure chlorine dioxide will be used as desinfectant.  The sample taking procedure will be repeated after one week of temporization (sterility tests  S3, S4 and root canal sample M2). The samples will be cultured and identified by MALDI-ToF  MS. The remaining samples will be used for PCR testing (Micro-IDent Plus11, Hain Lifescience)  to determine the presence of the tested bacteria. In the second session the root canal  obturation will be completed. Following coronal restoration a control x-ray will be done by  using an individual bite-block for standardization. The success of the root canal treatment  will be followed-up by evaluating the periapical status with the Periapical Index scoring  system and clinical evaluation according to the criteria set by the European Society of  Endodontology including pain assessment where the patients rate pain on the VNRS, with 0 =  ''no pain'' to 10 = ''worst pain imaginable". Clinical evaluation and control x-rays will be  done at 6 months, 1, 2, 3, and 4 years following treatment. The x-rays will be evaluated by  two blinded calibrated examiners. Inclusion Criteria:  • patients having asymptomatic chronic apical periodontitis of size 4-5 according to  periapical index scoring system Exclusion Criteria:  -  patients who suffer from diabetes, osteoporosis, cancer, autoimmue disease  -  patients who are in immune suppressed state  -  patients receiving steroid, bisphosphonate, denosumab or antiangiogenic therapy  -  alcoholism  -  smoking  -  patients having had antibiotic therapy in the past 4 weeks before starting treatment  -  teeth with furcation involvement  -  teeth with deeper than 4 mm probing depth or the same on neighboring teeth  -  patients intending to undergo prosthodontic or orthodontic treatment within four years

This is a pilot study to assess the feasibility of establishing a national  sero-epidemiological survey in England in individuals aged 0-24 years, focusing on assessing  humoral immunity against diphtheria, Group C invasive meningococcus and SARS-CoV-2. The  investigators will recruit 2800 to 3800 individuals, divided into three groups:  Group one (N= 2300):  This will include all age groups (0-24years), with recruitment restricted by postcodes  provided by Public Health England (PHE) to recruit a representative population for the region  as assessed by the IMD (Index of Multiple Deprivation scores).  Group two (N= up to 1200):  This group has been added following additional funding to enhance the sample size in response  to the COVID-19 pandemic. This will recruit 0-19 year olds and will not be restricted by post  code sampling. Instead recruitment will be by public promotion within the normal recruiting  regions for each site.  Group three (N= up to 300):  Addition of Group 3 which is enhanced surveillance in participants from Black, Asian or  minority ethnic groups (BAME). Since the start of recruitment we have noted that only 11% of  participants are from BAME population, despite recruiting in ethnically diverse regions.  Given the increased risk of COVID-19 disease in the BAME community, this is a potential  limitation of the study as it stands, not only because it may not reflect the diversity of  the UK population, but because it does not allow assessment of whether the differing disease  rates and seropositivity in adults are reflected in differences in seropositivity rates in  children. Similarly to Group 2, this will recruit 0-19 year olds and will not be restricted  by post code sampling. Public Health England has an ongoing sero-prevalence programme to assess how well the  population is protected from vaccine preventable diseases. The current way to check this is  by testing left over blood samples from participating healthcare laboratories around the  country. However, these samples may not be representative of the general population,  particularly in younger age groups who are often most at risk from vaccine preventable  diseases. In the Netherlands, they use a different system to assess how well the population  is protected from vaccine preventable diseases, actively collecting blood samples from a  representative cross section of society. This type of approach would address the limitations  of using residual serum samples and allows the collection of additional relevant history e.g.  number of family members and previous vaccines received. The investigators are therefore  proposing a pilot study to assess the feasibility of establishing a national sero-  epidemiological survey in England in individuals aged 0 - 24 years. The investigators will be  focusing initially on diphtheria and group C invasive meningococcal disease, both of which  are vaccine preventable. This will involve enrolling 2300 participants in the study from  different geographical and socioeconomic backgrounds across our test sites and taking a blood  sample. This blood will be analysed to look at the level of immunity to vaccine preventable  diseases.  The original protocol has been amended to include the testing of antibodies against other  infectious diseases, specifically COVID-19. A second group has been added to recruit an  additional 500 to 1200 participants between the ages of 0-19 years. The additional funding  has been used to open two more sites to recruit to group two across regions on England that  are currently not represented by this study. Having a large number of blood samples from a  range of age groups is useful when gathering information about an emerging disease such as  the current novel coronavirus (COVID-19). These samples can help provide answers regarding  the true number of infections with SARS-CoV-2 (the virus which causes COVID-19 disease) in  this population. Group 2 can be enhanced by the samples received from other ethically  approved research projects where participants have consented for their samples being used  outside of the study.  Additional funding has been granted for the addition of 300 participants from the BAME  community, who will form Group 3. Data from Group 3 would be invaluable in understanding  whether higher rates of disease in the BAME community are a result of greater exposure to  COVID-19 contact, a higher likelihood of being infected once exposed or a greater risk of  disease once infection occurs.  In addition to increasing the sample size and the number of regions in the UK that are being  sampled, a longitudinal sampling cohort has been introduced. A subset of participants equally  distributed over the age bands will be enrolled into the longitudinal aspect of the study  where repeat blood and saliva samples are taken to look for antibodies against SARS-CoV-2. A  questionnaire to ascertain whether the participant or any household contacts have had any  symptoms of or been tested positive for COVID-19 will also be collected.  A proportion of participants from this group from selected sites will also provide up to a  maximum of three blood samples for separation of peripheral blood mononuclear cells (PBMCs)  to evaluate T cell responses. These participants can be either seronegative or seropositive  at their Visit 1.  With the latter addition of four more sites, all NHS regions are now represented in the  study. Inclusion Criteria:  -  Parents/legal guardians or adult participant* is willing and able to give informed  consent for participation in the study.  -  Male or Female, aged 0 - 24 years inclusive (Group 1)  -  Male or Female, aged 0 - 19 years inclusive (Group 2)  -  Male or Female, aged 0 - 19 years inclusive with BAME background (Group 3)  -  Parents/legal guardians or adult participants are willing to allow their General  Practitioner or relevant NHS databases to be contacted for a full immunisation history Exclusion Criteria:  -  If participants do not live in the postcode districts selected by PHE (Group 1 only)  -  If participants are not from the BAME population (Group 3 only  -  Medically diagnosed bleeding disorder  -  Medically diagnosed platelet disorder  -  Anticoagulation medication  -  Pregnancy  -  If another member of their household is participating who is within 5 years of age of  the potential participants age  Temporary exclusion criteria:  The participant may not enter the study if they or any member of their household is under  temporary isolation measures for suspected SARS-CoV-2 infection.

ACLF and cirrhotic patient have deranged coagulation parameters and this coagulation  parameters altered when this group of patients undergoing dialysis because of renal failure.  this group of patients is also high risk of sepsis. Most common organ involved during sepsis  leading to organ failure is renal. So, all this cascade increases the risk of bleeding as  well as coagulation failure. Currently there are no studies evaluation the coagulation status  in patients with cirrhosis undergoing dialysis. Further there are no studies evaluating the  utility of these global tests of coagulation as a guide to judicious blood transfusion in  these patients to prevent bleeding. Further there are no studies comparing the two different  modalities of assessment. METHODOLOGY Aim: The incidence and predictors of bleeding diathesis development due to DIC in  cirrhosis and ACLF patients undergoing CRRT  Primary Objective:  Primary: Development of bleeding diathesis within 3 days [ e.g-bleeding/ooze from access  sites, GI bleeding (blood in ryles tube, hematemesis's, melena, bleeding PR), bleed form ET  tube site, bleed form nose/mouth or any other site]  Secondary Objective:  1. Assess the following factors as predictors of bleeding diathesis within 3 days:  -  Severity of liver disease: CTP, MELD, MELD-Na, APACHE, SOFA, AARC, lactate,  ammonia, [baseline and degree of change ,12 hrly,24 ,48 and 72 Hrly]  -  Presence and severity of AKI, HE [baseline and degree of change 12 hrly,24,48,72 or  at the detection of bleeding]  -  Presence and severity of infections/sepsis [baseline and degree of change 12 hrly  or at the detection of bleeding]  -  Complement levels (C3/C4) [baseline and degree of change at day 3 or at the  detection of bleeding]  -  Following test of coagulation system [baseline and degree of change 12  hrly,24,48,72 hrly and at the detection of bleeding [ Platelets counts (manual),  PT(INR), Prothrombin index, aPTT, Factor VIII/vWF , Fibrinogen, d-Dimer, FDP, DIC  score)  -  ROTEM (EXTEM,FIBTEM,APTEM,INTEM)  -  Type and dose vasopressors (NA, vaso, Terlipressin, somat, phenylep)  -  Hemodynamic parameters [pulse, BP, Lung water, SVV, SVR, CO/CI] optional  -  CRRT parameters [type of dialysate, membrane, flow,]  2. Survival by day 7  Study Population: Patients with cirrhosis or ACLF undergoing CRRT.  Study Design: A prospective study.  Study Period  -  The study will be conducted on patients admitted to Department of Hepatology from May  2021 to Aug 2021 at ILBS, New Delhi  -  Study group will comprise of patients with cirrhosis undergoing dialysis.  Sample size with Justification: There are no previous study to determine the bleeding risk in  ACLF or cirrhotic patient undergoing CRRT therapy so this is the pilot study so taking first  40 patients.  Intervention: There are no intervention arm. its prospective trial.  Monitoring and assessment: Investigator will be monitoring any bleeding epiosdes during the  CRRT and in case there are any bleeding risk the coagulation factors based upon ROTEM and  correct the coagulation abnormalties will be done.  Statistical Analysis:  -  All variables shall be expressed in median (range)  -  Variables will be compared by Mann- Whitney U test  -  For Categorical variables we will use Chi-Square or Fisher's test  -  Survival analysis will be done using cox-proportional regression analysis  Actuarial probability of survival shall be calculated by Kaplan- Meier graph and compared by  log- rank test.  Adverse Effects: increase risk of bleeding during CRRT  Stopping rule of Study: in case of bleeding not controlled with coagulation correction or  patient become hemodynamically unstable , negative consent for the further course of  treatment then study will be stopped .  Expected outcome of the project-.  Primary end points:  Incidence of dialysis related bleeding in first 24 hours  Secondary end points:  1. To assess correlation of ROTEM abnormalities with risk of clinically significant  bleeding  2. To assess the need and volume of FFP, Cryoprecipitate, platelet and packed red blood  cell transfusion based on ROTEM pre- and post-procedure  3. Incidence of transfusion associated lung injury and circulatory overload in both groups  at 24 hours  4. Incidence of infections (Time frame first 24 hours)  5. Incidence of infections and bleeding in first 7 days  6. Duration of hospital or ICU stay in both groups  7. 7 day mortality.  ROTEM would be done pre-procedure to assess the coagulation status for all patients enrolled  and subsequently post procedure and in case of bleeding, after transfusion at 12 hours and 24  hours, 48 and 72 hours respectively. Other standard blood tests would be done including  record of mean arterial pressures, CBC, KFT, LFT, PT/INR, arterial ammonia, lactate, serum  procalcitonin as required. In case of presence or absence of active bleed FFPs,  Cryoprecipitate, platelets will be transfused depending upon the coagulation parameters as  assessed by ROTEM . Inclusion Criteria:  - Consecutive patients with cirrhosis or ACLF undergoing their first session of dialysis Exclusion Criteria:  1. Age <12 or > 75 years  2. Hepatocellular Carcinoma  3. Recent history of blood product transfusion in the last 7 days  4. History of antiplatelets, antifibrinolytics or antithrombotics  5. Active untreated Sepsis/DIC  6. Any evidence of active bleed secondary to coagulopathy  7. Pregnancy  8. Comorbidities associated with poor outcome (Extrahepatic neoplasia, severe  cardiopulmonary disease defined by a New York Heart Association score >3, or  oxygen/steroid-dependent chronic obstructive pulmonary disease )  9. Refusal to participate in the study.

Surface Electromyography can be utilised to detect normal muscle electrical activity during  maximum forward flexion termed Flexion Relaxation Response (FRR) In this study, our primary objective is to assess FRR and disability (ODI) correlation  protocol as an objective tool in stratifying Chronic LBP. We also would like to evaluate the  relationship between FRR with pain intensity and lumbar range of motion as our secondary  objective. Inclusion Criteria:  -  Participants aged between 20 - 70 years old  -  Mechanical LBP > 6 weeks (not acute LBP)  -  Not received any specific exercise spinal manipulation or surgery to improve LBP  within the last 3 months. Exclusion Criteria:  -  Pregnancy  -  Radicular LBP patients or specific-spinal pathology / "red-flags".  -  Surgical intervention for the current LBP complaint (includes traumatic causes of LBP  with surgical intervention)  -  Cognitive or communication difficulty preventing active participation in exercises or  communicating pain scores

A prospective descriptive study of the use of an individualized capnography to each lung in  the context of one-lung ventilation achieved with a double-lumen tube.  - Pilot project and proof of concept  Brief Summary:  -  One study suggests a way to predict possible events of hypoxemia (Sat O2 < 90%) during  one lung ventilation (OLV) with the use of two individualized capnography devices on  each lung during two-lung ventilation before inducing OLV.  -  In addition, a recent presentation in the 2021 Thoracic Anesthesia Symposium suggested  possible benefits of the use of a capnography device on the non-ventilated lung in the  detection of air leaks around the bronchial cuff.  -  The same presentation demonstrated the utility of EtCo2 measurement to determine the  achievement of complete lung collapse.  With these previous demonstrations, the use of an individualized capnography for each lung  can potentially describe different steps during thoracic surgery. Therefore, a descriptive  prospective study on patients that require thoracic surgery with use of a double lumen tube  is proposed to verify the feasibility of dual capnography during OLV. The use of two  different devices, randomized during our study, will also help to identify the impact of  different air aspiration levels on our measures.  Such results will allow to put forward prospective projects to help to optimize OLV during  thoracic surgeries. Thoracic surgery (excluding cardiac surgery) requires lung isolation and one-lung ventilation  (OLV) to achieve unilateral lung collapse in order to complete the surgery.  One-lung ventilation requires the use of pulmonary isolation techniques. Two main isolation  techniques are used by clinicians: double-lumen tubes (DLT) and bronchial blockers (BB).  Bronchial blockers are less used than DLT.  Intra-thoracic interventions and consequently one-lung ventilation, are achieved in a lateral  decubitus, with the positioning of the operated hemi-thorax exposed. The most dreaded  complication during OLV is hypoxemia, which is defined as the desaturation in the patient's  oxygen (SpO2 under 90%). The primary goal of one-lung ventilation is to achieve a rapid and  complete lung collapse of the operated lung  Lung collapse is a technique that is well mastered and for which the investigators have  contributed significantly regarding its execution in our five of our most recent studies.  Recently, a presentation during the 2021 Thoracic Anesthesia Symposium raised our curiosity  regarding the induction of lung collapse (1) This presentation detailed the relevance and  possible benefits of adding a capnography on the isolated non-ventilated lung. According to  the authors, the capnography of the non-ventilated lung could potentially detect air leaks  towards the non-ventilated lung around the bronchial cuff and indicate the occurrence of  complete lung collapse.  In addition, an observational study demonstrated the utility of individualized capnography on  each lung during thoracic surgery with DLT (2). The measure of the exhaled CO2 gradient  between both lungs in a lateral decubitus position before one-lung ventilation could help  predict the oxygenation level during the subsequent one-lung ventilation.  The capnography is a tool that is used to monitor continuously the concentration of CO2 that  is inhaled and exhaled by intubated patients during general anesthesia (GA). The measures are  made with a device that samples a certain quantity of air volume inside a common circuit that  ensures the ventilation of both lungs. The sample is taken on a connector that is inserted in  the mechanical ventilation circuit. Many companies offer such devices. The intrinsic mechanic  is the same although the quantity of volume sampled can vary from one model to another.  (50mL/min to 200mL/min)  The use of individualized capnography of each lung seems to present potential benefits during  three key moments surrounding one-lung ventilation:  - During the period of time before one-lung ventilation, after the lateral positioning.  -  The gradient between the exhaled CO2 of both lungs could predict oxygenation levels  during one-lung ventilation.  -  During the ventilation of both lungs, the exhaled CO2 is proportional to the blood flow  in the pulmonary bed. During the ventilation of both lungs in the lateral decubitus  position, the blood flow may vary according to the initial perfusion of both lungs. The  effect of gravity caused by the patient's lateral position on the isolated  non-ventilated lung's perfusion allows for a better oxygenation. Other factors may also  influence the gradient. With that said, oxygenation levels during OLV could be  proportional to the difference of exhaled CO2 between both lungs during the lateral  decubitus position.  These results could change or conduct during OLV by anticipation of a possible desaturation  in oxygen, usually unpredictable.  - During the initiation of the one-lung ventilation  o The capnography is installed on the operated isolated and non-ventilated lung. This could  help confirm the quality of the lung isolation and guide our conduct in order to correct  inadequate isolation. The quality of the lung isolation depends on the adequate position of  the bronchial extremity of the left DLT in the main bronchus. It also depends on the  bronchial cuff's seal. In the beginning of OLV, fluctuations in the exhaled CO2 by the  isolated non-ventilated lung decrease and flatten. If there is an air leak around the  bronchial cuff in the main bronchus, the exhaled CO2 curve will show persistent fluctuations,  which would indicate a leak or inadequate seal.  The necessity of correction in the placement of the bronchial cuff and isolation could then  be guided by the observation of the exhaled CO2 curve.  - During one-lung ventilation  o During OLV, the capnography installed on the non-ventilation lung could help identify the  occurrence of complete lung collapse of the isolated lung. This aspect is an important  variable in each of our studies on this subject and is difficultly objectifiable.  The capnography could resolve this problem and help objectively identify total lung collapse.  Hypothesis  Our hypothesis concerning the principal goal of this study is that the measure of the exhaled  CO2 of the isolated and non-ventilated lung during thoracic surgery will have specific  characteristics for each of the steps described previously.  Our hypothesis concerning our secondary goal is that capnographs that have different levels  of aspiration will help us observe distinct exhaled CO2 characteristics.  Goals  Principal: Characterize the measures of exhaled CO2 during different steps of OLV for both  lungs (ventilated and non-ventilated).  Secondary: Evaluate the performance and reliability between two devices (high and low level  of air aspiration) of capnography on the measure of exhaled CO2 of both lungs during OLV.  Methods  In the context of this study, patients requiring elective thoracic surgeries requiring a OLV  will benefit from the addition of an additional capnography on the isolated non-ventilated  lung (non-dependent lung) from the anesthetic induction until the achievement of complete  collapse of the lung. The investigators will exclude patients in whom a bronchial blocker  will be used for OLV.  The information about age, sex, weight, height, VEMS, DLCO and surgical side was collected  for all the patients.  The capnography usually used at IUCPQ-UL will be placed on the ventilated lung circuit. The  capnography system under study will be installed on the circuit of the non-ventilated lung.  The ventilation will be adjusted according to the standards of practice at IUCPQ-UL.  During the study, two capnography machines with different aspiration levels will be  evaluated. They will be randomized before the induction of anesthesia, to assess the  effectiveness of each of these devices during the different peri-VUP assessment periods.  These devices are:  1. - GE Healthcare, CARESCAPE, Respiratory Modules Carbon dioxide (CO2) Sampling rate: 120  ± 20 ml / min  2. - Covidien, CAPNOSTREAM 35. Sampling rate: 50 + - 10 ml / min  The measures of exhaled CO2 for the ventilated and non-ventilated lung will be carried out  continuously and will be recorded on the various devices used, then transferred to a laptop  computer to be inserted into an Excel file. In addition, the ventilation parameters  (respiratory rate, end-tidal volume, 2-lung or single-lung ventilation, FiO2 and PEEP) will  also be collected manually. This data will then be retrieved and transferred to the Excel  file for further analysis.  Stages of observation  1. Period following induction of anesthetic in the supine position.  2. Period in lateral decubitus  1. Immediate (ventilation of both lungs)  2. After the start of the OLV until the opening of the pleura  3. From the opening of the pleura until achievement of complete collapse of the  isolated lung.  When the detection of exhaled CO2 is zero in the non-ventilated lung, which could indicate  complete collapse, a photo of the video screen showing an overall view of the lung will be  taken in order to qualify the lung collapse at that precise moment.  The description of the lung collapse will be done in this photo, according to our usual  criteria by an independent assessor after surgery.  The experimental period should last less than two hours.  Statistics Analysis  This study will require the recruitment of 30 patients divided into 2 groups of 15 subjects.  This number was determined based on the analysis of the results of a study published in 2009  by Yamamoto et al (8). The sample size was therefore calculated from the results obtained  concerning the exhaled CO2 between the two lungs during lateral decubitus positioning. This  is included in our primary assessment goal. It will take a total of 13 patients per group for  there to be a statistically significant difference with a p <0.05 and a power of 0.95.  Indeed, Yamamoto et al. obtained an exhaled CO2 of 36 ± 5 in the upper lung and 29 ± 5 in the  lower lung. The groups for each capnography will be rounded to 15 to obtain a total of 30  patients. If a post-randomization exclusion should occur, the capnography randomization will  be transferred to the next subject.  The collected data will first be analyzed in a descriptive manner with graphics in order to  interpret fluctuations in exhaled CO2 in the isolated lung. Subsequently, Student's T tests  will be carried out in order to compare the values obtained for each measurement time. These  comparisons will be made between the different periods and between the different capnographs  from the mentioned companies. Finally, the CO2 measures at the time of the picture of the  isolated lung will be correlated with the quality of the lung collapse as determined by an  independent assessor after the intervention.  Perspective  The investigators hope that the data collected during this research project will allow us to  demonstrate the potential benefits of an additional capnograph on the isolated lung during  OLV. Promising results from this easy-to-use technology could help predict the onset of  hypoxemia in some patients. In addition, the quality of lung isolation could be monitored  using this technology. Finally, if the exhaled CO2 is shown to be a potential marker of lung  collapse, this will standardize the subjective methodology currently used in the literature  in which the lung collapse is indicated by photos or videos of the lung. Such results will  allow us to put forward prospective projects already under development within our team. Inclusion Criteria:  -  Use of double-lumen tubes for isolation of the lung  -  Elective unilateral lung resection (anatomical segmentectomy, lobectomy or  pneumonectomy) for lung cancer Exclusion Criteria:  -  Use of bronchial blockers  -  IMC above 35

For patients with anterior cruciate ligament rupture, the existing physical examinations have  certain limitations. The researchers improved the traditional anterior drawer test in  clinical work, maintained the flexion of the knee and flexion of the hip, and observed the  displacement of the tibia. Good diagnostic effect, but no research statistics. The purpose of  this study is to explore the effectiveness of the 90° of hip flextion anterior drawer test in  the diagnosis of anterior cruciate ligament rupture. A total of 300 hospitalized patients who were diagnosed with anterior cruciate ligament  rupture by MR and prepared for anterior cruciate ligament reconstruction were included, of  which 150 cases were injured in the acute phase (within 2 months after the injury) and the  chronic phase (more than 2 months after the injury). After the patient was admitted to the  hospital, the patients were sequentially subjected to the 90° anterior drawer test, Lachman  test, pivot-shift test, and anterior drawer test. The examination results were recorded.  Compare the effectiveness of different physical examinations in diagnosing the anterior  cruciate ligament. The patient's age, gender, injury time, BMI, the type of ACL rupture in  the surgical records, and whether meniscus or cartilage damage were combined were counted.  Regression analysis was used to evaluate the influencing factors of the modified anterior  drawer test to correctly diagnose the rupture of the ACL. Inclusion Criteria:  -  （1）ages between 18 and 60 years old. (2) Inpatients diagnosed with unique anterior  cruciate ligament rupture and ready for anterior cruciate ligament reconstruction. (3)  no combined injuries. Exclusion Criteria:  -  (1) The patient is younger than 18 years old or older than 60 years old, (2) multiple  ligament injuries of the knee joint are suspected, and (3) combined fractures are  suspected.

This clinical trial is conducted to assess the long-term safety of "jointstem" in patients  with degenerative knee arthritis who participated in the previous BS-JS-IIT1 investigator  initiated trial. JOINTSTEM is injectables for an OA treatment that uses autologous adipose-derived mesenchymal  stem cells. As it does not use allogenic tissues and is cultured without additional genetic  modification, it is classified as 'autologous cell therapy' and is completely free of  immunologic rejection.  This clinical trial is planned to follow-up the long-term safety of "jointstem" in patients  with degenerative knee arthritis who participated in the previous BS-JS-IIT1 investigator  initiated trial.  Subjects who participate in the BS-JS-IIT1 study and agree to this extension test in writing  will be assessed for safety by conducting laboratory tests, vital signs, physical  examinations and adverse events every 12 months after Visit 1.  However, after unblinding of the BS-JS-IIT1 investigator initiated trial, subjects in the  control group (placebo administration) will terminate the follow-up of this extended clinical  trial and conduct routine treatment for degenerative knee arthritis at the discretion of the  researcher. Appropriate measures and follow-up observations shall be implemented for abnormal  reactions occurred during this extended test period until they are terminated (such as the  loss of the relevant adverse event or inability to conduct follow-up investigations). Inclusion Criteria:  -  Participants of Jointstem IIT by arthroscopy (BS-JS-IIT1)  -  Participants who signed informed consent document of this study Exclusion Criteria:  -  No applicable

Postoperative recovery after head and neck surgery is complex, and often requires utilization  of narcotic medications. The aim of this study is to evaluate reduction in pain and use of  opioid medications through Virtual Reality (VR) and Fitbit wearable activity devices. Enhanced Recovery After Surgery (ERAS) protocols were introduced as a method to optimize  perioperative patient care. Narcotic medications are frequently utilized in postoperative  care, but these have risks including sedation or dependence. Non-pharmacologic measures for  postoperative pain control may help limit the need for opioids in postoperative pain control.  Early mobilization is also important after surgery, however postoperative mobility is rarely  monitored and relies on subjective reports.  The investigators will seek to examine the implementation of an ERAS protocol using VR and  Fitbit wearable activity devices on postoperative recovery after head and neck surgery. This  is a prospective, 4-arm, randomized controlled trial. Inclusion Criteria:  -  English speaking  -  18 to 89 years of age.  -  Planned to undergo major head and neck surgery OHSU with an expected length of stay of  two days or more.  -  Ability to understand goals of the study and willingness to sign a written informed  consent document. Exclusion Criteria:  -  Planned postoperative admission to the intensive care unit (ICU).  -  Social or psychiatric conditions that may interfere with compliance.  -  Isolation precautions.  -  Reconstruction, incisions, wounds, wound care, or injury that impact the ability to  place on the VR headset or wear a Fitbit device around the wrist.  -  History of seizure or epilepsy.  -  History of vertigo or persistent dizziness.  -  Limitations that impair mobility.  -  Use of a walker or wheelchair at baseline.

Our overall purpose of this study is evaluate whether a short in-class Lyme Disease education  program based on social learning theory and the Health Belief Model can impact a child's  knowledge, attitude, and preventive behavior.  1. Deliver an educational program in schools to promote personal protective practices,  encourage early disease detection and modify residential habitats to reduce tick density.  3. Evaluate the program's efficacy by comparing the acceptability and practice of  precautionary behavior, tick density in residential areas and rates of Lyme disease between  groups using primary and surveillance data sources Evaluate the contribution of knowledge,  attitudes, and parental involvement to children's adoption of prevention strategies.  Hypothesis  The community intervention will reduce the incidence of Lyme disease among children and  families living in endemic areas by increasing the practice of precautionary behavior and  reducing tick density in residential areas. Specifically, we hypothesize that:  1. The educational intervention will reduce the incidence of Lyme disease among children  and families living in an endemic area.  2. The educational intervention will improve the childrens' self-confidence (behavioral  self-efficacy), intention to perform, and actual practice of Lyme disease prevention  behaviors. The description of Lyme disease in 1976 and subsequent characterization of its mode of  transmission, causative organism and treatment is one of the most remarkable advances in  medicine in the last 25 years1-3. Nevertheless, Lyme disease continues to grow as a public  health problem4. While Lyme disease affects all age groups, children have one of the highest  rates4. Prevention remains a challenge in this group. The Lyme vaccine has been withdrawn  from the market in February 20025, 6, and educational strategies among at-risk school  children have been inadequately evaluated and none have been institutionalized.  We will target school-aged children living in Nantucket, Dukes County and Essex County. We  have collaborated with the teachers and administration in many of the schools. We have  collaborated with the teachers and administration in many of the schools.  The intervention will be delivered by a member of our staff in conjunction with the teacher  as well as a health education entertainer ('Screaming with Pleasure Productions'). Research  assistants will distribute the enrollment questionnaires and "goody" bags. The basic content  of the educational message has been designed by Drs. Shadick, Liang, DeJong and the late Dr.  Daltroy, and has been used extensively on the Nantucket ferry study and in the "Feel Find  Free" Program. The timing takes advantage of the classroom audience, is humorous and  entertaining and the message is relevant to anticipated outdoor activities.  Primary Outcome: The educational intervention will reduce the incidence of Lyme Disease among  children and families living in an endemic area.  Secondary Outcomes: The educational intervention will improve the children's self-confidence  (behavioral self-efficacy), intention to perform, and actual practice of Lyme disease  prevention behaviors. Inclusion Criteria: None Exclusion Criteria: None

The project aims at assessing the role of radio-guided surgery in the detection of lymph node  invasion (LNI) in prostate cancer (PCa) patients undergoing radical prostatectomy (RP) by  using an intraoperative gamma probe and a radioactive labelled PSMA ligand (99mTc-PSMA-I&S).  We hypothesize that 99mTc-PSMA-I&S radio-guided surgery (99mTc-PSMA-RGS) might assist  physicians in the identification of patients with LNI candidate for an extended pelvic lymph  node dissection (ePLND). Overall, 100 men with a LNI risk >5% according to the Briganti  nomogram will be submitted to 68Ga-PSMA PET/MRI followed by 99mTc-PSMA-RGS and ePLND. The  aims are 1) to assess the safety and tolerability of 99mTc-PSMA-I&S; 2) to assess the  accuracy of 99mTc-PSMA-RGS in the identification of LNI compared to available clinical tools  and to molecular imaging (i.e., 68Ga-PSMA PET/MRI); 3) to assess whether 99mTc-PSMA-RGS would  allow for the identification of positive nodes outside the standard ePLND template. Potential participants will be identified, screened and recruited by the Urologists working  at the Department of Urology, IRCCS San Raffaele, Milan, Italy. A total of 100 patients  affected by PCa with a risk of LNI >5% according to the Briganti nomogram and planned to  receive RARP with an ePLND according to the European Association of Urology (EAU) guidelines  will be identified and enrolled in the study.  The patient must personally sign and date the latest approved version of the Informed Consent  Form (ICF) before any trial specific procedures are performed.  Written and verbal versions of the Patient Information and Informed Consent will be presented  to the participants detailing no less than:  -  The exact nature of the trial  -  The surgical procedures  -  The implications and constraints of the protocol  -  The known side effects and any risks involved in taking part  -  The clear statement that the participant is free to withdraw from the trial at any time  for any reason without prejudice to future care, and with no obligation to give the  reason for withdrawal.  The participant will be allowed as much time as wished to consider the information and the  opportunity to question the Investigator, their GP or other independent parties to decide  whether they will participate in the trial. Written Informed Consent will then be obtained by  means of participant dated signature and dated signature of the person who presented and  obtained the Informed Consent. The person who obtained the consent must be suitably qualified  and experienced, and have been authorized to do so by the Principal Investigator.  A copy of the signed Informed Consent will be given to the participant. The original signed  form will be retained at the trial Centre.  A Patient ID number will be assigned to each patient after the ICF signature: this number  corresponds to the Progressive Number assigned in chronological order beginning from 001  (i.e. 001, 002, etc.). For instance, the first patient enrolled will receive the following ID  Number: 001.  During Visit 1, the following data will be collected:  -  Demographics  -  Compliance with inclusion/exclusion criteria  -  Informed consent  -  Previous & concomitant pathologies/previous significant surgeries (including the  Charlson Comorbidity Index)  -  Previous & concomitant medications  -  Prostate cancer characteristics including PSA values, biopsy grade group, clinical stage  and the risk of LNI calculated according to the Briganti nomogram [12]  -  Vital signs  -  Laboratory testing (absolute neutrophil count; platelets; haemoglobin; serum creatinine)  The week before surgery patients will undergo a 68Ga-PSMA PET/MRI or PET/CT scan for  preoperative staging. Simultaneous PET/MRI will start 60 minutes after the  administration of approximately 160MBq of PSMA with the following protocol: localizer  MRI scans to define the number of table positions (PET-FOV) to acquire (4-min/table  position); specific attenuation correction and anatomical localization MR sequences at  each PET-FOV; pelvic mpMRI protocol according to European Society of Urogenital  Radiology guidelines. A positive 68Ga-PSMA PET/MRI will be defined as the presence of  any uptake at the level of the pelvic and/or retroperitoneal nodes. The results of this  procedure will not change the initially planned treatment.  99mTc-PSMA-I&S will be intravenously injected the day before surgery (day -1).  99mTc-PSMA-I&S will be prepared using a synthesis kit previously described [25].  SPECT/CT imaging will be performed the same day of treatment administration (day -1) to  document positive tracer uptake and will serve as quality control for tracer injection  and distribution.  All procedures will be performed through a trans-peritoneal approach using the Da Vinci Xi  (Intuitive Surgical, Sunnyvale, CA, USA) robotic Surgical System. The patient will be placed  in a Trendelenburg position. After incision of the peritoneum, release of the bladder  laterally to the endopelvic fascia, the ureter will be localized.  A drop-in gamma probe will be used for in vivo intraoperative measurements to identify  metastatic lesions at the level of the internal iliac, external iliac, obturatory and common  iliac stations. A positive finding at PSMA-RGS will be defined as the presence of a count  rate of at least twice as compared to the background reference (namely, fatty tissue of each  patient). All positive lesions (a count rate of at least twice as compared to the background  reference) will be excised. Ex vivo gamma measurements will be performed to immediately to  confirm the removal of the radioactive lesion or to prompt further search in case of a  missing signal. All the removed tissue will be collected separately according to the site of  resection. Inclusion Criteria:  -  Male patients  -  Age between 18 and 80 years  -  Biopsy proven PCa with a LNI risk >5% according to the Briganti nomogram  -  Planned to receive a RARP with an ePLND  -  Able to understand and willing to sign a written informed consent document Exclusion Criteria:  -  Receipt of neoadjuvant therapies  -  Inability to complete the imaging examinations according to the prospective protocol  -  Evidence of metastatic disease at conventional imaging before surgery  -  Evidence of clinical lymphadenopathies at conventional imaging before surgery  -  Life expectancy of less than 12 months  -  Previous chemotherapy  -  Previous brachytherapy or external beam radiotherapy  -  Unstable cardiovascular disease  -  Congestive Heart Failure (CHF)  -  Clinically significant hepatobiliary or renal disease  -  History of significant CNS injuries within 6 months  -  Any other significant disease or disorder which, in the opinion of the Investigator,  may either put the participants at risk because of participation in the trial, or may  influence the result of the trial, or the participant's ability to participate in the  trial  -  Medical history of allergic disease or reactions likely to be exacerbated by the IMPs  used in this study or by any of the components of the radiotracers (99mTc-PSMA-I&S and  68Ga-PSMA)  -  Patients who received an experimental drug in the context of clinical trials within 30  days from the administration of the radiotracers in the current investigation or  within 5 half-lives of the experimental drug itself

This study will evaluate the ability of dexamethasone to enhance labor epidurals when  administered as an adjunct to local anesthetics via an epidural catheter. Patients undergoing  elective cesarean sections will be randomized into three groups, each receiving the same  combined spinal epidural (CSE). At surgical closure, Group 1 will receive 10cc bupivacaine  0.0625%, Group 2 will receive 10cc bupivacaine 0.0625% +4mg dexamethasone, and Group 3 will  receive 10cc bupivacaine 0.0625% + 8mg dexamethasone (4mg). VAS, sedation, nausea, and  satisfaction scoring will be measured on patient follow-up to compare the outcomes of the  different treatment groups. This study will evaluate the ability of dexamethasone to enhance labor epidurals when  administered as an adjunct to local anesthetics via an epidural catheter. Patients undergoing  elective cesarean sections will be randomized into three groups using a random allocation  table. Group assignment will be performed by opening a previously prepared numbered opaque  envelope containing the assignment. Each group will receive the same combined spinal epidural  (CSE) containing 10-12mg hyperbaric bupivacaine, 150mcg preservative-free morphine, and 15mcg  fentanyl. At surgical closure, Group 1 will receive 10cc bupivacaine 0.0625%, Group 2 will  receive 10cc bupivacaine 0.0625% +4mg dexamethasone, and Group 3 will receive 10cc  bupivacaine 0.0625% + 8mg dexamethasone (4mg). In order to maintain this as a double-blinded  study, the patient will not be told which medication was administered and the drug will be  given by one anesthesiologist and the patient follow-up will be performed by a different  anesthesiologist. VAS, sedation, nausea, and satisfaction scoring will be measured on patient  follow-up to compare how these outcomes compare between the different treatment groups. Inclusion Criteria:  -  Parturients in their 3rd trimester who are receiving a planned cesarean delivery  -  Primiparous and multiparous pregnancies  -  American Society of Anesthesia (ASA) classes 1, 2 , and 3 Exclusion Criteria:  -  Patients for whom neuraxial anesthesia was either declined, unsuccessful, or  contraindicated  -  Gestational Diabetics  -  Diabetics  -  Patients allergic to dexamethasone, local anesthetics, or opioids  -  Patients that are immunosuppressed  -  Patient who received systemic steroids within the preceding 48 hours

The study is conducted to assess potential effectiveness and feasibility of a comprehensive  digital intervention for people with poorly-controlled Type 2 Diabetes Mellitus (T2DM), to  explore the intervention effects of a combined online and offline management for people with  T2DM and ultimately to improve the accessibility of lifestyle intervention among participants  with T2DM. The study is a single-arm, non-randomized clinical trial conducted to assess potential  effectiveness and feasibility of a comprehensive digital intervention for people with  poorly-controlled T2DM, to explore the 16 weeks intervention effects of a combined online and  offline management for people with T2DM and ultimately to improve the accessibility of  lifestyle intervention among participants with T2DM.  Primary objective is to study the proportion of participants with decrease in Hba1c by 0.6%  by providing digital based lifestyle modifications. Secondary objectives include to 1)  estimate the change in Hba1c, body mass index (BMI) and improvement in lipid profile  components at week 16 compared with baseline readings; 2) to evaluate of the use of the  Ramadan Risk Score (IDF-DAR Risk Stratification Scoring Tool); 3) to evaluate the rate of  fasting and diabetes complications (hyperglycaemia / hypoglycaemia) amongst Muslims with T2DM  during Ramadan. Inclusion Criteria:  -  participants diagnosed with T2DM;  -  HbA1c 7% and above in the latest blood test valid up to 12months prior to recruitment;  -  age range between 20-70 years old;  -  BMI between 23-50kg/m2 Exclusion Criteria:  -  Pregnant / Breast feeding participants  -  Participants on insulin therapy or non-insulin injectable medication  -  History of diabetes crisis (hyper or hypoglycaemia) in the past 6 months  -  Blood pressure ≥ 160/100 mmHg  -  Recurrent history of acute pancreatitis  -  Decompensated liver cirrhosis  -  eGFR <60ml/min/1.73m2  -  History of acute myocardial infarction/acute coronary syndrome(within the past 1  year), arrhythmias, heart failure (NY Class II -IV)  -  Proliferative diabetic retinopathy-Foot ulcer, gangrene  -  Deep vein thrombosis of lower limbs(within the past 12 months)  -  Intermittent claudication -History of cerebral haemorrhage or acute cerebral  infarction (within the past 12 months)  -  History of active cancer  -  Post-transplant/perioperative participants(defined as planned for operation for the  next 6 months)  -  History of hypo or hyperthyroidism, including subclinical states  -  Musculoskeletal injuries resulting in difficulty to perform physical activities  -  Failure to provide consent  -  Unable to perform activities of daily livings (ADLs)  -  Unable to use WhatsApp and YouTube via mobile devices, e.g. phone or tablet.

Postoperative delirium (POD) is a frequent postoperative complication in the elderly,  characterised by fluctuating disturbances in attention, awareness, and cognition. Identifying  the patients at highest risk of developing POD was the aim of the artificial intelligence  (AI)-based algorithm PIPRA. This prospective cohort study is to externally validate the  AI-based PIPRA algorithm. The primary endpoint is the performance (AUC) of the PIPRA  algorithm in predicting POD. The secondary endpoint is the performance (AUC) of the  clinicians in predicting POD (and how it compares with the performance of the PIPRA  algorithm). Perioperative neurocognitive disorders (PND) include postoperative delirium (POD) and  postoperative neurocognitive disorder or postoperative cognitive dysfunction (POCD). POD is  recognised as a frequent postoperative complication in the elderly, occurring in 10% to 50%  of older patients after major surgical procedures. POD usually occurs in the early  postoperative period and is defined as an acute neuropsychiatric disorder. It is  characterised by fluctuating disturbances in attention, awareness, and cognition. The  American Society of Enhanced Recovery and Perioperative Quality Initiative Joint Consensus  Statement on Postoperative Delirium Prevention recommend focusing on identifying those  patients at highest risk of developing POD. Identifying these highest risk patients was the  aim of the artificial intelligence (AI)-based algorithm PIPRA, which was created based on an  individual participant data (IPD) meta-analysis including more than 2500 patients. This  risk-prediction algorithm uses standard data (i.e. age, height, weight, history of delirium,  cognitive impairment, ASA status, number of medications, preoperative C reactive protein  (CRP), surgical risk and laparotomy), which are routinely collected before surgery. PIPRA was  internally validated with an area under the curve (AUC) of 0.837 with 95% confidence interval  0.808 to 0.865, when plotting the true positive rate against the false positive rate. The aim  of this prospective cohort study is to externally validate the AI-based PIPRA algorithm.  First, the anaesthesiologist in charge will be asked to evaluate, based on his/her experience  (quantified in years of anaesthesia practice), the risk for the included patient to develop  POD (categorised as low, intermediate, high or very high). Next, an investigator will assess  included patents in a systematic and reproductible manner. After surgery, an investigator  will visit the patient twice daily from postoperative day 1 to 5 or until hospital discharge  (whichever occurs first) to screen for delirium using the 4AT or the ICDSC. The PIPRA score  will be calculated separately by the coordinating study centre. Inclusion Criteria:  -  Surgical patients ≥60 years old  -  Planned postoperative hospital stay ≥ 2 days  -  Consent from patient Exclusion Criteria:  -  Preoperative delirium  -  Insufficient knowledge in German or French  -  Intracranial surgery  -  Cardiac surgery  -  Surgery within the two previous weeks  -  Patient unable to consent

The aim of the study is to evaluate the effects of intermittent  hypoxic-hyperoxic training (IHHT) to protect myocardium against perioperative  myocardial injury during cardiac surgery using cardiopulmonary bypass. This is a prospective, single-center, randomized controlled clinical trial, which will  involve patients over 18 years old who would be recruited consecutively during pre-admission  consultation at the I.M Sechenov First Moscow State Medical University Cardiac Surgery  Department. All patients with a diagnosis of valvular heart disease, or aortic arch disease  and indications for cardiac surgery, according to the European Society of Cardiology/European  Association for Cardio-Thoracic Surgery guidelines.  Five days before the operation, patients will be randomly assigned into two groups using a  computer-generated randomization table: intermittent hypoxic-hyperoxic training and an  intermittent hypoxic-hyperoxic training control group. For both groups laboratory testing  (specific biomarkers - C-reactive protein, troponin I, fatty acid-binding protein (FABPs) and  lactate) will be performed before training and after the surgery, and the hypoxic-inducible  factor (HIF 1 alpha) would be implemented before and after the trainings.  Patients in the intermittent hypoxic-hyperoxic training group will undergo four daily  procedures of interval hypoxic-hyperoxic training before cardiac surgery, using a normobaric  device to obtain hypoxic and hyperoxic gas mixtures (ReOxy Cardio; Aimediq S.A., Luxemburg,  Registration certificate in RU P3H 2014/1486). Before the start of the training, each patient  would undergo a hypoxic test to assess the individual response to hypoxia, and to determine  the rate of reduction of blood oxygen saturation (SpO2) with a finger pulse oximeter (Masimo  SET, measurement accuracy ±2%). During 5 minutes the patient will receive air with reduced  oxygen content (12%), through a mask under constant monitoring of the heart rate (HR) and  SpO2. As a safety measure, minimal SpO2 would be set at 82% and maximal accepted increase of  heart rate would be set to +50% of the initial heart rate. When these values would be  reached, the supply of oxygen automatically would be switched to a hyperoxic gas mixture  (35%-40% O2), inhaling of which would be continued until SpO2 reached 100% (even if SpO2 was  lower before the procedure), therefore depending on the rate of saturation reduction, will be  taken 1 to 3 minutes (mean 1 min and 50 seconds). The intention is to create hyperoxic  arterial oxygen tension and not to simply reduce the time required to recover from hypoxia.  Intermittent hypoxic hyperoxic training would be considered successful if there were no  significant side effects during the procedure such as angina pain, loss of consciousness,  severe dizziness or other variants of significant subjective deterioration of the patient's  condition. In the case of successfully passing the test, patients will proceed to the basic  intermittent hypoxic hyperemic training. During the training, the hypoxic gas mixture will be  given to the patient again in intermittent mode, based on the individual test parameters and  alternating with the supply of a hyperoxic gas mixture. One cycle of the procedure consists  of hypoxic and hyperoxygenated intervals, the duration of which will be regulated  automatically according to the biofeedback principle, based on monitoring of individual  values of SpO2 and heart rate. The duration of the hypoxic period ranges from 3 to 5 minutes,  and the duration of the hyperoxic period ranges from 1 to 3 minutes, depending on the SpO2  recovery rate. The total time of the hypoxic gas mixture inhaled during one procedure will be  20-30 min. A final training would be conducted in the evening before the surgery. Patients in  the intermittent hypoxic-hyperoxic training - control group also will undergo four daily  procedures before surgery, using 40 min training periods with simulation of intermittent  hypoxic-hyperoxic training by using the same equipment, the patient receives moistened air  through a placebo mask under constant monitoring of heart rate and SpO2. Only the person who  will conduct the training would know about the patient's allocation to a particular  intervention group, the anesthesiologists and cardiac surgeons will not have access to this  information. Episodes of cardiac arrhythmias, hypotension with a need for inotropic drug  prescription, changes in electrocardiogram, pulse values and blood pressure levels will be  recorded during surgery and the postoperative period.  Patients will be monitored for 7 days in the hospital, and 30 days after discharge to  evaluate the complications.  Differences between groups will be assessed using the unpaired Student's t-test or the  one-tailed Anova test followed by the Bonferroni post-test. Baseline corrected logistic  regression models will be used to estimate the training effect in relation to primary and  secondary endpoints. Statistical significance will be set at 0.05 to test hypotheses. Inclusion Criteria:  -  1. Written consent to participate in the study 2. Male or female patients over 18  years 3. Indications for planned replacement of the aortic or mitral valves or  operations on the aortic arch. Exclusion Criteria:  -  1. Individual intolerance to the intermittent hypoxic-hyperoxic training  2. Acute coronary syndrome after hospitalization and before the surgery  3. The presence of an acute infectious process after hospitalization and before the  surgery (fever, leukocytosis with a shift leukocyte formula to the left, increased  erythrocyte sedimentation rate (ESR), increased C-reactive protein)  4. Uncompensated hypertension at the time of the procedure (systolic blood pres-sure  more than 160 mm Hg, diastolic blood pressure more than 110 mm Hg)  5. Loss of consciousness, severe dizziness  Non-inclusion criteria:  1. Occlusive atherosclerotic disease of lower limbs,  2. Acute coronary syndrome within 4 weeks before entry  3. Preoperative renal insufficiency (serum creatinine higher than 200 mmol/L),  4. Acute infectious diseases  5. Partial and secondary generalized forms of epilepsy,  6. Uncompensated hypertension (Blood pressure at the time of the procedure: systolic  blood pressure more than 160 mm Hg, diastolic blood pressure more than 110 mm Hg)  7. Severe bronchial asthma with the development of respiratory failure of the II-III  degree and individual intolerance to oxygen deficiency.  9. Severe hepatic impairment (class C child-Pugh) Intervention type  10. Mental illness (if patients are not capable of understanding the nature, significance  and implications of the clinical trial)  11. Myocardial insufficiency as a component of multiple organ failure in decompensation of  liver and kidney diseases

Use of antenatal corticosteroids therapy has increased since the 2000s. The benefits of such  a therapy on premature newborns are scientifically and internationally recognized.  Nevertheless, few studies have been conducted to investigate the impact of this antenatal  corticosteroid therapy on full-term newborns (> 36 weeks' gestation).  The aim of this study is to compare the birth parameters of full-term newborns exposed or not  to antenatal corticosteroid therapy. All children included in the study were born at the Regional Maternity Hospital of Nancy  between January 1, 2014 and December 31, 2020.  One hundred and twenty-one of them were exposed during pregnancy to antenatal corticosteroids  therapy and constitute the exposed arm, whereas 242 were not and constitute the non-exposed  arm.  Data were collected retrospectively regarding history of pregnancy, birth parameters and  neonatal adaptation. Inclusion Criteria:  -  all children exposed to an antenatal corticosteroid therapy before 34 weeks of  amenorrhea because of a threat of premature delivery  -  only full-term newborns Exclusion Criteria:  -  all children exposed to an antenatal corticosteroid therapy before 34 weeks of  amenorrhea for other reasons

The BAP1 trial will examine the blood of patients diagnosed with choroidal nevi or uveal  melanoma for a germline BAP1 mutation and other genetic markers associated with developing  malignancy as well as additional sequencing of the uveal melanoma genome. A germline BAP1 mutation predisposes a person to developing uveal melanoma and other cancers.  If a mutation is discovered, it changes the potential approach to managing the nevus. In the  presence of a known genomic change associated with aggressive disease, closer follow up and  more aggressive treatment could preserve the patient's vision and prevent micrometastatic  spread. This new screening technique will be able to extend the length and quality of life of  patients with more frequent targeted cancer screens. Inclusion Criteria:  any person with choroidal nevi  -  Willingness to provide signed informed consent  -  Age > 18 years  -  Diagnosis of choroidal nevi or uveal melanoma  Threre are no exclusionary criteria for this study. Exclusion Criteria: None

0116-ASG REMETY is a multicenter, open-label, non-randomized, dose-escalation Phase I study  evaluating the safety and anti-tumor activity of TAS-102 administered in combination with  Regorafenib in patients with metastatic colorectal cancer. The primary objective is to determine safety, feasibility and the recommended phase II dose  (RP2D) of a combination treatment consisting of TAS-102 and Regorafenib in subjects with mCRC  who have progressed after standard therapy. Inclusion Criteria:  1. Written informed consent and any locally-required authorization (EU Data Privacy  Directive in the EU) obtained from the subject prior to performing any  protocol-related procedures, including screening evaluations  2. Age ≥ 18 years at time of study entry  3. Histological or cytological documentation of adenocarcinoma of the colorectal region  (CRC)  4. Metastatic disease not amenable to surgical resection with curative intent  5. Study treatment must constitute 3rd-line treatment for metastatic disease. Prior  treatment lines must encompass at least one fluoropyrimidine-based chemotherapy, an  anti-VEGF and, in case of RAS wildtype tumors, an anti-EGFR treatment.  6. Patients treated with oxaliplatin in an adjuvant setting need to have progressed  during or within 6 months of completion of adjuvant therapy to be counted as prior  treatment line. Note: Neoadjuvant, perioperative or adjuvant regimens with progression  more than 6 months after completion are not considered as prior treatment line for  metastatic disease.  7. Measurable disease, defined as at least one unidimensional measurable lesion on a CT  scan as defined by RECIST 1.1  8. Eastern Cooperative Oncology Group (ECOG) performance status <2 and life expectancy of  at least 3 months  9. Adequate bone marrow, renal, and hepatic function, as evidenced by the following  within 7 days prior to study treatment initiation:  -  Absolute neutrophil count (ANC) ≥1,500/mm3  -  Platelets ≥100,000/mm3  -  Hemoglobin ≥9.0 g/dL  -  Serum creatinine ≤1.5 x upper limit of normal (ULN)  -  Glomerular filtration rate (GFR) ≥30 mL/min/1.73m2  -  AST and ALT ≤2.5 x ULN (≤5.0 × ULN for patients with liver involvement of their  cancer)  -  Bilirubin ≤1.5 X ULN  -  Alkaline phosphatase ≤2.5 x ULN (≤5 x ULN with liver involvement of their cancer)  -  Amylase and lipase ≤1.5 x ULN  -  Spot urine must not show 1+ or more protein in urine or the patient will require  a repeat urine analysis. If repeated urinalysis shows 1+ protein or more, a  24-hour urine collection will be required and must show total protein excretion  <1000 mg/24 hours  -  INR/PTT ≤1.5 x ULN (Patients who are therapeutically treated with an agent such  as warfarin or heparin will be allowed to participate provided that no prior  evidence of underlying abnormality in coagulation parameters exists. Close  monitoring of at least weekly evaluations will be performed until INR/PTT is  stable based on a measurement that is pre-dose as defined by the local standard  of care.)  10. Women of childbearing potential and male subjects must agree to use adequate  contraception for the duration of study participation and up to 6 months following  completion of therapy. Females of childbearing potential who are sexually active with  a non-sterilized male partner must use 2 methods of effective contraception from  screening, and must agree to continue using such precautions for 6 months after the  final dose of investigational product.  11. Female subjects must either be of non-reproductive potential (ie, post-menopausal by  history: ≥60 years old and no menses for ≥1 year without an alternative medical cause;  OR history of hysterectomy, OR history of bilateral tubal ligation, OR history of  bilateral oophorectomy) or must have a pregnancy test performed at a maximum of 7 days  before start of treatment, and a negative result must be documented before start of  treatment.  12. In the assessment of the investigator, patient is able to comply with study  requirements.  13. Subject is willing and able to comply with the protocol for the duration of the study  including undergoing treatment and scheduled visits and examinations including follow  up. Exclusion Criteria:  1. Prior treatment with Regorafenib, or any other tyrosine kinase inhibitor for the  treatment of malignancy  2. Prior treatment with TAS-102  3. Previous or concurrent cancer that is distinct in primary site or histology from  colorectal cancer within 5 years prior to study inclusion EXCEPT for curatively  treated cervical cancer in situ, non-melanoma skin cancer and superficial bladder  tumors [Ta (Non invasive tumor), Tis (Carcinoma in situ) and T1 (Tumor invades lamina  propria)].  4. Known history of/or concomitant malignancy other than mCRC likely to affect life  expectancy in the judgment of the investigator  5. History of Gilbert's syndrome  6. Major surgical procedure, open biopsy, or significant traumatic injury within 28 days  and last chemotherapy <21 days prior to first dose of treatment  7. Radiotherapy within 4 weeks prior to first dose of treatment  8. Active cardiac disease including any of the following:  -  Congestive heart failure (New York Heart Association NYHA) ≥Class 2  -  Unstable angina (angina symptoms at rest), new-onset angina (within the last 3  months).  -  Myocardial infarction less than 6 months before start of Day 1 of treatment.  -  Cardiac arrhythmias requiring anti-arrhythmic therapy (beta blockers or digoxin  are permitted)  -  Uncontrolled hypertension. (Systolic blood pressure >140 mmHg or diastolic  pressure >90 mmHg despite optimal medical management)  9. Arterial or venous thrombotic or embolic events such as cerebrovascular accident  (including transient ischemic attacks), deep vein thrombosis or pulmonary embolism  within 6 months before start of treatment  10. Known history of human immunodeficiency virus (HIV) infection  11. Chronic hepatitis B or C infection (If hepatitis status can not be obtained from  medical records re-testing is required.)  12. Patients with seizure disorder requiring medication  13. Symptomatic metastatic brain or meningeal tumors unless the patient is >6 months from  definitive therapy, has a negative imaging study within 4 weeks prior to treatment  initiation, and is clinically stable with respect to the tumor at the time of study  entry. Also, the patient must not be undergoing acute steroid therapy or taper  (chronic steroid therapy is acceptable, provided that the dose is stable for one month  prior to and following screening radiographic studies).  14. History of organ allograft  15. Evidence or history of bleeding diathesis. Any hemorrhage or bleeding event ≥ Grade 3  (CTCAE v. 4.0) within 4 weeks prior to the start of study treatment.  16. Non-healing wound, ulcer or bone fracture  17. Renal failure requiring hemo- or peritoneal dialysis  18. Dehydration according to CTCAE v. 4.03 Grade >1  19. Substance abuse, medical, psychological, or social conditions that may interfere with  the patient's participation in the study or evaluation of the study results  20. Known hypersensitivity to any of the study drugs, study drug classes, or any  constituent of the products  21. Known dihydropyrimidine dehydrogenase (DPD) deficiency or treatment with DPD  inhibitors, including sorivudine or its chemically related analogues such as brivudine  within 4 weeks prior to the start of study treatment.  22. Interstitial lung disease with ongoing signs and symptoms at the time of informed  consent.  23. Inability to swallow oral medications  24. Any malabsorption condition  25. Unresolved toxicity higher than Grade 1 CTCAE v. 4.03 attributed to any prior  therapy/procedure excluding alopecia, anemia and oxaliplatin-induced neurotoxicity  (which must be ≤Grade 2) or ongoing infection >Grade 2.  26. Patients unable or unwilling to discontinue (and substitute if necessary) use of  prohibited drugs for at least 2 weeks prior to Day 1 of treatment initiation.  27. Female subjects who are pregnant, breast-feeding or intent to become pregnant  28. Any condition that, in the opinion of the investigator, would interfere with  evaluation of study treatment or interpretation of patient safety or study results  29. Participation in another clinical study with an investigational product during the  last 30 days before inclusion  30. Previous enrollment in the present study (does not include screening failure).  31. Involvement in the planning and/or conduct of the study (applies to Bayer staff and/or  staff of sponsor and/or staff of the CRO and study site)  32. Patient who might be interconnected with or dependent on the sponsor, site or the  investigator Patient who has been incarcerated or involuntarily institutionalized by  court order or by the authorities § 40 Abs. 1 S. 3 Nr. 4 AMG.

The aim of this study is to investigate whether a tDCS-accompanied intensive cognitive  training is feasible as a home-based intervention. The goal of the present study is to assess feasibility (primary) and cognitive training and  transfer effects of a home-based multi-session cognitive training combined with transcranial  direct current stimulation (tDCS). tDCS, particularly in combination with cognitive training,  represents a promising approach to counteract cognitive decline and restore impaired  functions. However, combined interventions of cognitive training and tDCS involve frequent  visits to the facility, which leads to the need of space, time and personnel, and imposes  strains on the participants. This study will elucidate the feasibility of tDCS and cognitive  training in a home-based context. Healthy older adults will participate in a two-week  cognitive training with concurrent online tDCS application in their own homes. Feasibility,  as well as cognitive performance will be examined before, during and after the intervention.  In order to draw conclusions about the effect of tDCS in addition to cognitive training, a  control group, receiving sham stimulation during training, will be assessed. A Follow-up  session to assess long-term effects is planned four weeks after the post assessment. We  hypothesize that with appropriate training of the participants and close supervision the use  of combined tDCS and cognitive training in an ecologically valid environment by the  participants themselves is feasible. In addition, we hypothesize this protocol will lead to  improved performance on the trained tasks in both experimental groups. We expect increased  performance on transfer tasks and long-term maintenance of the effects after anodal compared  to sham stimulation. A successful implementation of the intervention in the home-based  setting will contribute to the development of home-based tDCS as a widely available therapy  option in clinical populations. Inclusion Criteria:  1. Age: 60 - 80 years  2. Right handedness Exclusion Criteria:  1. Neurodegenerative neurological illnesses, epilepsy or history of seizures  2. Severe and untreated medical conditions that preclude participation in the training,  as determined by responsible physician  3. History of severe alcoholism or use of drugs  4. Severe psychiatric disorders such as depression (if not in remission) or psychosis  5. Contraindication to tDCS application

Although, effective immunotherapies for MS exist which downregulate the anti-myelin  reactivity and reduce the rate of relapses of the disease, there is no effective means today  to stop the progression of disability and induce remyelination. Neuronal stem cells were  shown to possess the ability to restore neuronal activity and produce new neurons through  transdifferentiation. Various other types of stem cells were tested in animal models with  promising results, revealing a potential for restoration of the neurological function in  neuroimmune and neurodegenerative conditions. Adult bone marrow derived stromal cells (MSC)  were shown to induce similar (to neuronal stem cells) immunomodulatory and neuroregenerative  effects and were shown in our laboratory to induce neuroprotection in the animal model of  chronic experimental autoimmune encephalomyelitis (EAE). MSCs offer practical advantages for  clinical therapeutic applications, since they can be obtained from the adult bone marrow and  therefore the patient can be the donor for himself, without any danger for rejection of the  cells. In addition, MSCs carry a safer profile and are less prone to malignant  transformation.  Our initial clinical experience with 10 patients with ALS and 10 with multiple sclerosis show  that intravenous and intrathecal administration of MSCs is feasible and safe.  In this study we propose an explorative protocol with the injection of MSCs (both  intrathecally and intravenously) in patients with MS, in an effort to prevent further  neurodegeneration through neuroprotective mechanisms and induce neuroregeneration and  restoration of neuronal function.  The primary endpoint will be to further evaluate the safety and feasibility of the treatment  with MSC infusions, in MS patients. Additionally, the migration ability of the transplanted  cells will be evaluated by tagging MSCs with the superparamagnetic iron oxide particle  (Feridex) for detection by MRI. Clinically the patients will be followed by monthly  evaluations of the MS functional rating scale (EDSS) scale. The MRI, will be also used to  evaluate changes in the total volume of lesions in the brain and the degree of atrophy.  Significance: This project may provide information for possible therapeutic uses of this type  of bone marrow adult stem cells in MS but may also serve as a pilot platform and pave the  path for future applications of various types of stem cells in neurodegerative diseases, in  general. This study, is designed as a phase 1/2 open-safety clinical trial. At its first phase, 15  consenting patients with MS are included.  Inclusion Criteria:  Consenting patients fulfilled the following 4 inclusion criteria for this study:  1. the clinical criteria of Poser et alfor definite MS;  2. men and nonpregnant women aged 25 to 65 years;  3. duration of disease longer than 5 years; and  4. failure to respond to the currently available and registered agents for MS (ie,  interferons, glatiramer acetate [Copaxone], and immuno-suppressors), as manifested by an  increase of at least 1 degree in the EDSS score during the past year or the appearance  of at least 2 major MS relapses during the same period.  Exclusion criteria:  1. patients who were treated with cytotoxic medications (ie, cyclophosphamide,  mitoxantrone, and azathioprine) during the 3 months before the trial;  2. patients with significant cardiac, renal, or hepatic failure or any other disease that  may interfere with the ability to interpret the results of the study;  3. patients with an active infection; and  4. patients who showed severe cognitive decline or were unable to understand and sign the  informed consent.  Bone marrow aspiration is performed under short general anesthesia with puncture from the  posterior superior iliac crest while the patient was lying in a left or a right lateral  position. Approximately 200 mL of bone marrow inocula are obtained from each patient.  MSC Preparation and Culture A culture of purified MSCs is prepared under aseptic conditions  (positively pressurized clean rooms) using filtered sterilized Dulbecco modified Eagle medium  with low glucose lev- els (Qiagen, Valencia, California) supplemented with 10% fetal bovine  serum, 1% L-glutamine, and 1% penicillin-streptomycin- nystatin solution (all from Biological  Industries, Kibbutz Beit- Haemek, Israel).  Mesenchymal cells are cultured for 40 to 60 days, until they reach confluency, and then  harvested and cryopreserved in 10% dimethyl sulfoxide-containing medium in liquid nitrogen  (-196°C). At 2 weeks, a sample is taken for sterility testing and quality control. After  sterility confirmed, the MSCs are transferred to the laboratory on dry ice, thawed in a 37°C  water bath, and washed twice with normal saline solution to remove any residual dimethyl  sulfoxide. The cells are then resuspended in normal saline at a concentration of 10x106/mL to  15x106/mL. Two-thirds of the total number of cells (usually 60x106 to 100x106) are injected  intrathecally, and one-third, intravenously. A sample of the cells to be injected is tested  by fluorescence-activated cell sorter (FACS) analysis; cells (98%) should express the surface  markers characteristic of MSCs (CD29, CD73, CD90, CD105, and CD166) and be negative for CD34,  CD45, and CD14.  Treatment Protocol All patients receive an intrathecal injection via a standard lumbar  puncture (mean of 1 million cells per Kg of body weight) and an intravenous injection of  0.3-1 million cells per kg, intravenously..  An extension phase is scheduled for patients completing the first phase of this trial as an  open prospective study with repeated intrathecal or intravenous injections of autologous MSC  in patients from the initial trial and 10 additional ones (total up to 24 patients) with  progressive forms of MS (secondary progressive, primary progressive or  relapsing-progressive). Patients should be defined as failures to first and second lines of  immunomodulatory treatments experiencing deterioration (at least 0.5 degree in the EDSS  scale) during the year preceding their inclusion to our study or had at least one major  relapse without sufficient recovery. Patients will be treated with 1x10 million MSC per kg of  body weight, intrathecally and intravenously and subsequently with up to 8 courses of IT- or  IV-injections of MSC (at the same dose), at intervals of 6-12 months. The duration of the  trial is 4 years.  Patients will be followed up every 3 months for the whole duration of the trial, for safety  assessment and changes in the disability scores (EDSS).  Immunological analysis will be performed at 4 time points (day 1, month 1, month 3 and month  6) following the first MSC-treatment and will include a fluorescent cell sorter (FACS)  analysis to evaluate the proportions of the lymphocytes expressing markers of immune  activation or of regulatory cell phenotype. Inclusion Criteria:  1. Consenting patients fulfilling the Poser's clinical criteria for definite MS  2. Age: 35-65, males and females  3. Duration of disease: >5 years  4. Failure to the currently available -registered- for MS immunomodulatory treatments (ie  interferons, Copaxone, immunosuppression): the lack of response to (at least two) of  these treatments will be determined/defined by either an increase (deterioration) of  at least one degree in the EDSS score during the last year or the appearance of at  least two major relapses of MS during the same period of time (under treatment). Exclusion Criteria:  1. Patients who were treated with cytotoxic medications (cyclophosphamide, Mitoxanthrobne  etc) during the last 3 months prior to the inclusion  2. Patients suffering from significant cardiac, renal or hepatic failure or any other  disease that may risk the patient or interfere with the ability to interpret the  results  3. Patients with active infections  4. Patients with severe cognitive decline or inability to understand and sign the  informed consent

This grant award entitled, "Cerebrovascular Reactivity and Oxygen Metabolism as Markers for  Neurodegeneration after Traumatic Brain Injury" (hereafter, "Neurovascular Study"), aims to  determine if neurovascular contributors to neurodegeneration can serve as markers of the  emergence or progression of degenerative processes after traumatic brain injury in  middle-aged and older adults. This grant award entitled, "Cerebrovascular Reactivity and Oxygen Metabolism as Markers for  Neurodegeneration after Traumatic Brain Injury" (hereafter, "Neurovascular Study"), aims to  determine if neurovascular contributors to neurodegeneration can serve as markers of the  emergence or progression of degenerative processes after traumatic brain injury in  middle-aged and older adults. Primary outcomes are cerebrovascular reactivity (CVR), as  measured by functional Magnetic Resonance Imaging (MRI) Blood Oxygen Level Dependent (BOLD)  and cerebral metabolic rate of oxygen (CMRO2) as assessed by the novel MRI sequence called,  "T-2 Relaxation-Under-Spin-Tagging" (TRUST). After the baseline primary endpoints are  acquired, a single dose of sildenafil 50mg will be given to assess for the effects of a  hypercapnia task on CVR and CMRO2. Other outcomes measured include additional imaging  sequences (diffusion, ASL), volumetric analysis, and neuropsychological tests. Inclusion Criteria:  -  Ages 50-80 years  -  Eligible for Washington, DC Veterans Affairs Medical Center (VAMC) research  participation  -  Capacity to provide consent to participate in research (assessment made by study  neurologist and PI)  -  Ability to read and write English  • History of traumatic brain injury of sufficient severity to have resulted in medical  attention ascertained via the Ohio State University TBI Identification Questionnaire (OSU  TBI-ID). TBI defined by Departments of Defense/Veterans Affairs (DoD/VA) criteria.  • No history of traumatic brain injury of sufficient severity to have resulted in medical  attention ascertained via the OSU TBI-ID, and no TBI based upon DOD/VA criteria. Exclusion Criteria:  -  History of penetrating brain injury  -  History or evidence of disabling neurological or psychiatric condition such as  epilepsy (besides posttraumatic epilepsy), multiple sclerosis, hypoxic-ischemic  encephalopathy, encephalitis, or schizophrenia  -  History or evidence of cortical or subcortical stroke  -  History or evidence of diabetes mellitus requiring therapy (Hemoglobin A1c > 9.0% for  purposes of this study)  -  History or evidence of uncontrolled hyperlipidemia. For the purposes of this study,  "hyperlipidemia" will be defined as total cholesterol of 230 in the presence of either  or both diabetes and hypertension and 300 in the absence of both of these conditions.  Statin therapy with normal cholesterol levels is allowed.  -  History or evidence of uncontrolled hypertension (defined as systolic pressure > 160  and/or diastolic pressure > 110 mmHg), or hypotension (systolic pressure < 110 and/or  diastolic pressure < 65 mmHg). Hypertension controlled with a single anti-  hypertensive medication is allowed.  -  Untreated atrial fibrillation  -  Active tobacco use  -  MRI incompatibility  -  If a participant is currently or has previously taken a phosphodiesterase inhibitor  (PDESi), then a two week washout period is required immediately prior to the  evaluation visit.  -  Use of nitrates

There are major health disparities in Blacks associated with high blood pressure (BP) and  psychosocial stress. We evaluated the effects of lifestyle modification with meditation in  Black adults with high normal and normal blood pressure.  Participants (n=304) were randomized to either the Transcendental Meditation technique or  Health Education control in addition to usual care for up to 36 months for BP and secondary  outcomes. Background: Blacks suffer from disparities in hypertension, cardiovascular disease (CVD) and  currently, coronavirus-19. These conditions are associated with social determinants of health  and psychosocial stress. While previous trials demonstrated stress reduction lowering blood  pressure in grade I range in Blacks, there is a paucity of clinical trial data in Blacks with  high normal and normal BP.  Objective: This randomized controlled trial was conducted to evaluate the effect of stress  reduction with the Transcendental Meditation (TM) technique in Black adults with high normal  BP and normal BP using International Society of Hypertension (ISH) definitions.  Methods: A total of 304 Black adults with high normal (130-139/85-89 mm Hg) and normal BP  (120-129/80-84 mm Hg) were randomized to either TM or health education (HE) arms. BP was  recorded at 3, 6, 9, 12, 24, 30, and 36 months after baseline. Linear mixed model analysis  was conducted to compare the BP change between TM and HE participants in the high-normal BP  and normal-BP groups. Survival analysis for hypertensive events was conducted. Inclusion Criteria:  -  self-identified Black women and men  -  no current antihypertensive medications  -  high normal BP (130-139 mm Hg and/or DBP 85-89 mm Hg) OR  -  normal BP (SBP 120-129 mm Hg and/DBP 80-84 mm Hg) Exclusion Criteria:  -  use of antihypertensive medications within the previous 2 months  -  history of CVD, ie, myocardial infarction, angina, peripheral artery disease, heart  failure, stroke, or renal failure, diabetes, major psychiatric or substance use  disorder other life-threatening illness  -  lack of signed a consent form

This phase II trial studies how well positron emission tomography (PET)/computed tomography  (CT) and single positron emission computed tomography (SPECT)/CT imaging works in improving  radiation therapy treatment in patients with stage IIB-IIIB non-small cell lung cancer.  PET/CT imaging mid-way through treatment may be able to accurately show how well radiation  therapy and chemotherapy are working. SPECT/CT imaging may be able to tell which parts of the  lung tissue are healthier than others. Based on the result of the imaging, treatment  adjustments may be made to the radiation therapy to improve survival and decrease toxicity. OUTLINE: This is a dose-escalation study of radiation therapy.  Patients undergo functional avoidance radiation therapy during weeks 1-3. Patients undergo  fludeoxyglucose F-18 FDG PET/CT at baseline, 3 weeks, and 3 months post-radiation therapy and  undergo technetium Tc-99m albumin aggregated (99mTc-MAA) and technetium Tc-99m sulfur colloid  SPECT/CT radiation therapy at baseline and 3 months post-radiation therapy. Baseline PET/CT  must be performed at University of Washington Medical Center/Seattle Cancer Care Alliance and  be within one month of treatment start, therefore some patients may need to repeat a baseline  PET/CT if their PET/CT is from an outside institution or > 1 month old. Patients not  responding to treatment at 3 weeks, will receive an increased daily radiation therapy dosage.  After completion of study treatment, patients are followed up for 2 years. Inclusion Criteria:  -  Pathologically proven (either histologic or cytologic) diagnosis of stage IIB-IIIB  non-small cell lung cancer (NSCLC); according to American Joint Committee on Cancer  (AJCC) staging, 7th edition  -  Staging workup must include: brain imaging (CT head or magnetic resonance imaging  [MRI] brain) and PET/CT  -  Pleural effusions must have cytology to rule out malignant involvement unless too  small to undergo thoracentesis per radiology  -  Patients must be considered unresectable or inoperable  -  Patient must not have received prior radiation for this lung cancer  -  Patients must be having concurrent chemotherapy  -  Nodal recurrences can be treated on this protocol but prior curative surgery for lung  cancer must have been at least 6 months prior to the nodal recurrence  -  Patients must have measurable or evaluable disease that is FDG avid with standardized  uptake value (SUV) > 3 on PET/CT  -  Zubrod performance status 0-1  -  PFTs including forced expiratory volume in 1 second (FEV1) within 26 weeks prior to  registration; for FEV1, the best value obtained pre- or post-bronchodilator must be >=  0.8 liters/second or >= 50% predicted  -  Blood cell count (CBC)/differential obtained within 8 weeks prior to registration on  study  -  Absolute neutrophil count (ANC) >= 1,800 cells/mm^3  -  Platelets >= 100,000 cells/mm^3  -  Hemoglobin >= 10.0 g/dl (Note: The use of transfusion or other intervention to achieve  hemoglobin (Hgb) >= 10.0 g/dl is acceptable)  -  Serum creatinine within normal institutional limits or creatinine clearance >= 40  ml/min  -  Bilirubin must be within or below normal institutional limits  -  Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) < 2.5 x the  institutional upper limit of normal (IULN)  -  Patient must sign study specific informed consent prior to study entry Exclusion Criteria:  -  > 10% unintentional weight loss within the past month  -  Prior invasive malignancy (except non-melanomatous skin cancer) unless disease free  for a minimum of 3 years; non-invasive conditions such as carcinoma in situ of the  breast, oral cavity, or cervix are all permissible  -  Prior radiotherapy to the region of the study cancer that would result in overlap of  radiation therapy fields  -  Pregnancy or women of childbearing potential and men who are sexually active and not  willing/able to use medically acceptable forms of contraception

The goal of this study is to survey retention procedures used by French orthodontists, and  evaluate the needs for practice guidelines. The hypothesis is that there is no consensus  among orthodontists, requiring practice homogenization via expert guidelines. Similar studies  have been driven in others European countries (such as Swiss, the Netherlands, Lithuania and  Norway), but not in France. Questionnaire aggregating 27 questions on orthodontic retention strategies, was sent to a  professional list of French orthodontists from health authorities. The survey was composed of  eight parts, about sociodemographic status, retention system selection, choice of fixed and  removable retention system, retention period, supervision, given instruction and needs for  practice guidelines. Inclusion Criteria:  -  All French Specialist orthodontists trained in France who answer the survey Exclusion Criteria:  -  Non-specialist orthodontists, not trained in France

Unnecessary opioid prescriptions for postoperative pain can increase the risk for new,  persistent opioid use and dependence. Published literature suggests that most patients  undergoing thyroid or parathyroid surgery can have their pain effectively managed without  opioids following hospital discharge. The purpose of this quasi-experimental, quality  improvement study is to develop, implement, and measure the impact of a quality improvement  bundle that consists of (1) patient education, (2) provider education, and (3) electronic  health record (EHR) enhancements. The proportion of patients who receive new opioid discharge  prescriptions for pain management following thyroid or parathyroid surgery at Houston  Methodist Hospital for up to 6 months following bundle implementation will be compared to a  historical control group. BACKGROUND: New and persistent opioid use after minor and major surgery is common, and the  duration of opioid use following surgery is associated with opioid dependence, abuse, and  overdose. Most patients undergoing thyroid or parathyroid surgery do not require opioid  discharge prescriptions for effective pain management. If opioids are prescribed for these  surgeries, up to 7% of patients will use opioids 3 to 6 months after surgery. Previously  published quality programs that optimized perioperative multimodal analgesia (MMA) regimens,  provider education, patient education, and shared decision making successfully reduced the  proportion of patients discharged with opioid prescriptions to less than 5% following thyroid  and parathyroid surgery.  STUDY DESIGN: This quasi-experimental, quality improvement study compares opioid discharge  prescribing practices before and after implementation of the quality improvement bundle. The  quality improvement bundle includes patient education, provider education, and EHR  enhancements. Patients who undergo a thyroidectomy or parathyroidectomy procedure will be  included in the study. The historical control group includes patients treated prior to bundle  implementation. The post-implementation group includes patients treated within 4 to 6 months  following bundle implementation. The primary outcome is the proportion of patients who  receive new opioid discharge prescriptions at discharge following a thyroidectomy or  parathyroidectomy procedure. This outcome excludes the continuation of previous, chronic  opioid therapy. Inclusion Criteria:  -  Adult patients undergoing a primary thyroidectomy or parathyroidectomy procedure at  Houston Methodist Hospital during the study period. Only index surgeries during the  study time frame were included. Exclusion Criteria:  -  Patients with a hospital length of stay after surgery >2 days

The purpose of the study is to investigate if there are common biopsychosocial vulnerability  factors for developing and maintaining fatigue, regardless of the diagnosis. The  investigators also believe that subgroups differ in terms of these factors. Participating  patients with ME/CFS, burnout syndrome and post-covid fatigue complete a web form at  inclusion and after 1, 2, 4, 6, 12, 18 and 24 months. There is no upper limit for the number  of participants in the web survey. 150 participants are asked to submit blood samples at a  local laboratory in connection with the questionnaires for analysis of inflammatory markers  and one urine sample for analysis of nutritional markers. Two control groups are included,  150 patients with rheumatoid arthritis and 50 healthy individuals. The longitudinal design  makes it possible to investigate how inflammatory markers, nutritional status, symptom  burden, health related quality of life co-vary over time and how work ability and sick leave  is affected. Fatigue is associated with impaired health and severely impaired quality of life and function  and there is a need to explore similarities and differences regarding biopsychosocial  vulnerability and maintenance factors and consequences in terms of work ability and sick  leave in chronic fatigue syndrome (ME / CFS), burnout syndrome (BS) and post-covid fatigue to  be able to improve individualized interventions for patient with persistent fatigue. The  study examines inflammatory markers, nutritional status, symptom burden, neuropsychiatric  conditions, work ability, and sick leave in a longitudinal cohort study over 2 years in  patients with different diagnoses who all suffer from persistent fatigue. The hypothesis is  that there are common biopsychosocial vulnerability factors for developing and maintaining  fatigue, regardless of the diagnosis. The investigators also believe that subgroups can be  identified that differ in terms of these factors. The longitudinal design makes it possible  to investigate how inflammatory markers, nutritional status, symptom burden, health related  quality of life co-vary over time and how work ability and sick leave is affected.  In this study participating patients with ME/CFS, BS and post-covid fatigue complete a web  form at inclusion and after 1, 2, 4, 6, 12, 18 and 24 months.  Adult patients registered with a diagnosis of chronic complicated fatigue (ME/CFS or  post-covid syndrome) in Take Care (medical record system in Stockholm County, Sweden) or with  burnout syndrome from Stressmottagningen Stockholm, will be asked to participate in the  study.  -  Patients with ME/CFS will be recruited at the Department of Behavior Medicine,  Karolinska University Hospital Solna or reached by advertising on social media  -  Patients with Post-covid-syndrome will be recruited at Karolinska University Hospital or  reached by advertising on social media  -  Patients with burnout syndrome will be recruited at Stressmottagningen Stockholm  At baseline, a clinical assessment is performed at the clinic and the patient is asked to  leave a venous blood sample and complete a questionnaire. The patients are asked for further  blood samples and questionnaires at 1, 2, 4, 6, 12, 18, and 24 months after baseline. 150  participants, 50 in each diagnostic group, are asked to submit blood samples for biobanking  at a local laboratory in connection to the questionnaire time points for analysis of  inflammatory markers. C-reactive protein (CRP) is analysed at the time of blood samples. They  are also asked to give one urine sample for analysis of nutritional markers and to submit a  3-day diet diary for evaluation of dietary intake by a registered dietitian. Participants  that only fill out the web-based questionnaire will be included. There is no upper limit for  the number of participants in the web survey.  A pilot study with 20 participants with ME/CFS started in 2018 to test and revise the design  of the present study. These subjects will be counted in the group of 50 participants with  ME/CFS diagnosis when available data allow.  In addition to the participants with persistent fatigue, two control groups are included in  the study. 150 patients with rheumatoid arthritis (RA) recruited from the Karolinska  University Hospital Rheumatology department and 50 healthy controls. The RA controls fill out  the illness generic questionnaires on paper and disease information is taken from the  national registry for rheumatic disease and CRP and erythrocyte sedimentation rate (ESR) data  is taken from the medical record. The healthy controls follow the same procedure as the  patients with persistent fatigue but only fill out the form and give blood samples at one  time point.  Research questions:  -  Are there differences in patient reported fatigue dimensions, symptom burden including  post exertional malaise, sleep disorders, health related quality of life, or  inflammatory markers, nutritional markers and dietary intake, between patients with  ME/CFS, BS and post-covid fatigue, patients with RA and healthy controls?  -  Are inflammatory markers and nutritional status associated with the development/recovery  of fatigue and symptom burden in ME/CFS, BS and post-covid fatigue?  -  Can different subtypes of patients be identified based on latent factor analysis  including fatigue dimensions, symptom profile, neuropsychiatric symptoms, inflammatory  markers and nutritional status?  -  How does inflammatory markers, nutritional status, symptom burden and health related  quality of life influence work ability and sick leave in patients with persistent  fatigue over time?  The project group consists of a multidisciplinary team from Stockholm and Linköping  universities as well as clinically active at clinics in the two regions who often meet  patients with persistent fatigue. Inclusion Criteria:  -  Diagnosis set within Stockholm County of ME/CFS, burnout syndrome or  post-COVID-19-syndrome according to the Swedish version of the international  classification of disease (ICD)-10  -  Control group (rheumatic disease): Diagnosis of rheumatoid arthritis  -  Control group (healthy): no diagnosis related to inflammatory disease or fatigue Exclusion Criteria:  -  Organic or neuropsychiatric disease that explain the fatigue among cases diagnosed  with ME/CFS, burnout syndrome or post-COVID-19-syndrome according to the Swedish  ICD-10

Frailty is a multidimensional condition due to reserve loss leading to physical and cognitive  impairment that is very common in older adults; in fact, its incidence increases with age.  Frail older adults present a high risk of adverse events such as disability, hospitalization  and mortality. It is very important to check comorbidities and complications to reduce the  incidence of cognitive and physical impairment. Frailty is a multidimensional condition due to reserve loss leading to physical and cognitive  impairment that is very common in older adults; in fact, its incidence increases with age.  Frail older adults present a high-risk of adverse events such as disability, hospitalization  and mortality. It is very important to check comorbidities and complications to reduce the  incidence of cognitive and physical impairment; hence, clinical evaluation is the main goal  to get an early diagnosis and a timely treatment for cognitive impairment. Considering this  background, the study will investigate the effects of nutraceuticals and drug treatment on  cognitive impairment in frail older adults. In this scenario, global cognitive function will  be evaluated with Mini Mental State Examination (MMSE) and Montreal Cognitive Assessment  (MoCA) test and physical impairment with the Fried criteria and 5-metres gait speed test. Inclusion Criteria:  -  age > 65 years;  -  a frailty status. Exclusion Criteria:  -  age < 65 years.  -  no frailty status.  -  left ventricular ejection fraction <25%, with previous myocardial infarction or  previous PPCI or/and coronary by-pass grafting.

This project assesses the feasibility and usability of the geriatric assessment platform  (electronic Geriatric Assessment Platform or eGAP in 50 older patients with cancer, their  caregivers, and their oncology team. Using an iterative process, we will refine the eGAP  based on input from stakeholders. A geriatric assessment is a multidisciplinary diagnostic process that can detect medical,  psychosocial and functional problems not identified by routine evaluation. This can  subsequently guide management of the identified problems. However, the time and resources  required to incorporate a geriatric assessment into clinic visits remain the primary barriers  for implementation. There is a need to increase the adoption of the geriatric assessment  among general oncologists and to address the associated resource limitations. Our long-term  goal is to utilize an electronic platform to facilitate completion of the geriatric  assessment. This project assesses the feasibility and usability of the geriatric assessment  platform (electronic Geriatric Assessment Platform or eGAP) in 50 older patients with cancer,  their caregivers, and oncology providers. Using an iterative process, we will refine the eGAP  based on input from stakeholders (patients, caregivers, oncologists, nurses, advanced  practitioners) Inclusion Criteria:  -  Age ≥65 years  -  Have a diagnosis of cancer  -  Able to provide informed consent  -  English-speaking (because the platform is currently in English)  -  Age ≥21 years  -  Selected by patient when asked if there is a "family member, partner, friend, or  caregiver with whom you discuss or who can be helpful in health-related matters".  -  Able to provide informed consent  -  English-speaking  -  Oncologists, APPs, and nurses who care for the patient Exclusion Criteria:  -  N/A

In recent years, Cognitive Behavioral Therapy has been integrated with mindfulness meditation  (CBT-M) following evidence for increased efficacy when modalities are combined. We will  assess whether online group CBT-M plus standard psychiatric care is non-inferior in efficacy  and more cost-effective than office-based, on-site group CBT-M (plus standard psychiatric  care) per outcomes at post-intervention and at 6-month follow up in adults with major  depressive disorder (MDD). This non-inferiority randomized controlled trial will employ both  assessor-blinded and self-report outcome measures and will include a full economic  evaluation. Depression is a commonly diagnosed mental health disorder that represents the most prevalent  cause of disability worldwide. Cognitive Behavioural Therapy (CBT) is the best-evidenced  treatment for depression, but despite demonstrated efficacy, many individuals cannot access  adequate psychotherapeutic treatment due to the limitations of face-to-face delivery. In  recent years, CBT has been integrated with mindfulness meditation (CBT-M) following strong  evidence for increased efficacy when the two modalities are combined. Previous RCTs have  demonstrated that online CBT-M is effective in depressive symptom reduction, but direct  comparisons to in-office CBT delivery assessing cost and treatment outcomes are required to  facilitate innovation and clinical policy change.  Objectives: To assess whether online group CBT-M plus standard psychiatric care is  non-inferior in efficacy and more cost-effective than office-based, on-site group CBT-M (plus  standard psychiatric care) per outcomes at post-intervention and at 6-month follow up in  adults diagnosed with major depressive disorder (MDD). The study will assess whether  digitally recorded adherence data (i.e. online workbooks completed, Fitbit tracked step  count, online text-messages exchanged, phone sessions completed) predict outcome benefits in  the online-group participants as measured by changes in depressive symptoms.  Methods: This single-centre, 2-arm non-inferiority randomized controlled trial will employ  both assessor-blinded and self-report outcome measures and will include a full economic  evaluation.  The research site is the Centre for Addiction and Mental Health (CAMH), a large  research-based psychiatry institution located in Toronto, Canada. Participants will be  identified from wait-lists for CAMH services and through contacts with other Toronto  outpatient clinics.  Interventions: All participants will receive standard psychiatric care (1 pharmacotherapy  focused visit/month with a psychiatrist of 15-30 minute duration). Experimental participants  additionally receive online CBT-M while control participants receive standard care in-office  group CBT-M. The online group CBT-M program (in collaboration with NexJ Health, Inc.)  combines exposure to smartphone and computer accessed workbooks with phone-based mental  health counselling (16 hours in 16 weeks) that coordinates with ongoing software interactions  (e.g. secure text messaging, Fitbit tracked walking). Each participant is loaned a Fitbit-HR  Charge 3 to assess physical activity as measured by daily step count. Inclusion Criteria:  -  Beck Depression Inventory-II of at least mild severity (BDI-II score ≥ 14) with no  upper severity limit;  -  Psychiatrist diagnosis of Major Depression Disorder;  -  MINI International Neuropsychiatric Interview-confirmed diagnosis of Major Depression  Disorder;  -  fluent in English. Exclusion Criteria:  -  individuals currently receiving weekly structured psychotherapy;  -  individuals who meet DSM-V criteria for severe alcohol/substance use disorder (in the  past 3 months), borderline personality disorder, schizophrenia or any other primary  psychotic disorder, bipolar disorder or obsessive-compulsive disorder;  -  individuals who manifest clinically significant suicidal ideation defined as imminent  intent or attempted suicide (in the past 6 months);  -  individuals who are judged to have treatment resistant depression (TRD), as defined by  failure in at least two trials of antidepressant medications and/or a course of  psychotherapy during the current depressive episode

Background:  There is general agreement that statin-treatment of patients to lower plasma cholesterol  levels can increase the incidence of type 2 diabetes mellitus (T2D) in some individuals1-5.  The physiologic mechanism for the increased risk for T2D from statin treatment is unknown but  could result from effects on insulin sensitivity or insulin secretion. This study will  evaluate how the medication atorvastatin (trade name Lipitor) works in non-diabetic  individuals in regards to its effect on insulin sensitivity and insulin secretion to help  further understand the possible cause of the increased occurrence of T2D in people who are at  risk for T2D. This research study will also examine what metabolic characteristics and  variables (for example insulin resistance, high triglycerides, or both) will identify those  people at highest risk of statin-induced T2D.  The goals of this study are to:  1. determine the effect of high-intensity atorvastatin (40 mg/day) for ~ 10 weeks on  insulin sensitivity and insulin secretion (defined with gold standard methods) (PRIMARY  OUTCOMES) as well as other glycemic traits (SECONDARY OUTCOMES);  2. compare a number of cardio-metabolic characteristics (e.g. weight, lipids) before,  during, and after administration of atorvastatin;  3. determine if significant deterioration of insulin action and/or secretion following  statin treatment will be confined to those with baseline insulin resistance  (PRE-SPECIFIED SUBGROUP ANALYSES);  4. perform Personal Omics Profiling (iPOP) 6,7 before and after taking atorvastatin to  examine treatment-associated changes in all baseline variables and to analyze not only  previously-known drug efficacy but also untargeted drug efficacy (EXPLORATORY ANALYSES).  General approach:  This will be an open-label study to evaluate the diabetogenic effect of atorvastatin (40  mg/day for 10 weeks) on both insulin action and insulin secretion in nondiabetic individuals.  To ensure we recruit individuals across a broad range of insulin sensitivity, we will target  recruitment to enrich for those with combined increases in LDL-C and TG concentrations (see  SIGNIFICANCE and RATIONALE). The experimental population will consist of ~75 apparently  healthy, non-diabetic volunteers eligible for statin therapy but without pre-existing  atherosclerotic cardiovascular disease. Following baseline assessments of co-primary outcome  measures: insulin sensitivity (by insulin suppression test, IST) and insulin secretion (by  graded glucose infusion test, GGIT), participants will be placed on a weight maintenance diet  and treated with 40 mg/day of atorvastatin. All baseline measurements will be repeated ~10  weeks later with iPOP8 measurements done at baseline, at weeks 2, 4, and 10 on atorvastatin,  and at weeks 4 and 8 off atorvastatin. 1. SIGNIFICANCE  Statins and the risk of T2D: Statin treatment is associated with an increase in incident  T2D.1-4 5  Mechanism of statin-induced T2D: It is unclear whether statins increase the risk of T2D  by decreasing insulin action, secretion, or both. Several manuscripts have been  published that substantially increase understanding of the link between statin use and  incident T2D. Swerdlow, et al.2 based on evidence from genetic analysis and randomized  trials, concluded that the increased risk of T2D noted with statins is at least  "partially explained by HMG-coenzyme A reductase (HMGCR) inhibition." They also noted an  association of weight gain with HMGCR variants in statin-treated patients, leading to  the notion that decreases in insulin sensitivity contribute to statin-induced diabetes.  In that context, Cederberg, at al.9 have shown in a large prospective study (n=8749 men)  that participants treated with statins (n=2142) had a 46% increase in incident T2D,  associated with a 24% decrease in insulin sensitivity and a 12% decrease in insulin  secretion assessed by surrogate measures.  Identifying those with at enhanced risk of statin-induced T2D: Studies of 3 randomized  clinical trials with atorvastatin by David Waters' group 1,3,4 have demonstrated that  "baseline fasting glucose, body mass index, hypertension, and fasting triglycerides were  independent predictors of T2D." These abnormalities form a cluster attributed to insulin  resistance.10 Since insulin resistance is a predictor of developing T2D, it seems likely  that the more insulin resistant the individuals are before treatment, the greater is  their risk to for statin-induced T2D.  In that context, relatively little attention has been given to the role that metabolic  heterogeneity in patients with elevated LDL-C concentrations might play in  statin-induced T2D. Specifically, subjects with elevated LDL-C concentrations, whose  plasma triglyceride (TG) concentrations are also elevated, are insulin resistant,  hyperinsulinemic, and glucose intolerant as compared to those with isolated LDL-C  levels. As such, this subset of patients with elevated LDL-C concentrations can be  viewed as being at a "tipping point," and any adverse effect of statins on insulin  action and/or secretion, irrespective of how mediated, places them at enhanced risk to  develop statin-induced diabetes. Indeed, we have shown (Kohli et al)1 that patients with  both insulin resistance (as estimated by high TGs) and prediabetes are at particularly  high risk of statin-induced T2D.  We seek to address 2 important unanswered questions: Do statins primarily affect insulin  resistance or insulin secretion?; Are there subsets of individuals at highest risk of  statin-induced T2D?  2. RATIONALE, HYPOTHESIS  Rationale:  T2D develops when insulin resistant individuals cannot maintain the degree of  compensatory hyperinsulinemia needed to maintain normal glucose tolerance. However,  significant fundamental questions remain. For example, what is the cellular/molecular  link between statin treatment and changes in insulin action and secretion?  This proposal is based on the premise that studying the effect of statins on insulin  action and insulin secretion using "gold standard" methods will help determine if  statins adversely affect the risk of T2D by increasing insulin resistance or decreasing  insulin secretion. We use the insulin suppression test (with the read-out of  steady-state plasma glucose, SSPG) to ascertain insulin sensitivity and the graded  glucose infusion test (with the readout of insulin secretion rate, ISR) to ascertain  insulin secretion both before and after statin treatment in non-diabetic individuals.  We hypothesize that treatment with atorvastatin 40 mg/day for approximately 10 weeks  will impair insulin sensitivity and/or insulin secretion and that this effect may be  exacerbated in those with underlying insulin resistance. Thus, we plan to look at the  effect of atorvastatin not only in all participants but also in subsets of individuals  with baseline insulin resistance (which will be enriched for by recruiting volunteers  with elevated plasma TG levels (≥150 mg/dL) at baseline. The rationale for this is that  plasma TGs are a surrogate measure for insulin resistance with a modest correlation with  the direct measure of insulin resistance (steady-state plasma glucose) measured by the  insulin suppression test. Clinically, subjects with elevated TGs prior to statin  treatment would have substantial clinical benefit from statins, and one of  investigators' secondary goals is to demonstrate that a simple measurement of plasma TG  concentration (as a surrogate for insulin resistance) can help identify those most at  risk of statin induced derangements in glycemic control. Consequently, we propose to  enroll nondiabetic volunteers at high-risk for T2D, free of known atherosclerotic  cardiovascular disease (ASCVD), not receiving statins, eligible for statin therapy  according to ACC/AHA (American College for Cardiology/American Heart Association) 2013  guidelines.11 We will also target recruitment efforts to enrich for subjects with plasma  TG concentration ≥ 150 mg/dL to ensure that we enroll subjects across the range of  insulin sensitivity.  Hypothesis: We hypothesize that high intensity atorvastatin treatment for approximately  10 weeks will impair insulin sensitivity and/or insulin secretion and that this effect  may be exacerbated in those with underlying insulin resistance.  3. STUDY DESIGN  Sample Size  • We aim to recruit and retain 75 total participants in this study.  Study Location  • Clinical and Translational Research Unit (CTRU) at 800 Welch Road, Palo Alto, CA  94304.  Duration  • We anticipate that the entire study will take 4 - 5 years through the end of data  analysis. Each eligible candidate who voluntarily consents to participate in the study  will be active in the study for a total of 5 months from screening to the end of their  last visit.  4. STUDY PROCEDURES  Recruitment  Preliminary recruitment strategies will include:  Volunteers will be recruited from the San Francisco Bay Area through advertisements in  newspapers, posted flyers, and the social networking site NextDoor as well as from the  Preventive Cardiology Clinics at Stanford Health Care. Our goal is to ensure recruitment  across a broad range of insulin sensitivity. Prior work from our group and others has  shown that high plasma TG concentrations are associated with increased insulin  resistance as assessed by reference measures. Therefore, we will target advertisements  to enrich for individuals with high TG levels (> 150 mg/dL) as a surrogate for increased  insulin resistance.  Participant Visits and Procedures  Potential participants will be screened initially when they call or email in response to  recruitment ads, or a letter from their MD, describing the study as follows:  Preliminary intake will occur over the phone.  Visit 1 Screening visit.  Visit 2: Oral Glucose Tolerance Test (OGTT): This test will take approximately 3 hours.  i) Glycemic status: Participants will be classified as having normal glucose tolerance  (NGT), isolated impaired fasting glucose (IFG), isolated impaired glucose tolerance  (IGT), or combined IFG/IGT12. In addition, the total integrated plasma glucose response  during the OGTT will be calculated by the trapezoidal method (Glucose-AUC).  ii) β-cell function: Calculations of the Insulin Secretion- Sensitivity Index-2 (ISSI-2)  will be used to quantify insulin secretory function 13, if for some reason a graded  glucose infusion study is not done. The ISSI-2 is a validated OGTT- derived method to  measure of β-cell function, analogous to the disposition index obtained from the  intravenous glucose tolerance test 14. It is calculated by multiplying the insulin  secretory response during the OGTT (Insulin-AUC/Glucose-AUC) by insulin resistance  (Matsuda index).  The fasting and 2-hour glucose results will be discussed with the study participant and  a copy of the results will be given to them.  Visit 3. Graded Glucose Infusion, GGIT 15,16: This test will take approximately 6 hours.  This test is designed to assess the ability of the pancreas to produce insulin in  response to a graded glucose infusion. During this test, subjects will have two small IV  catheters placed, one in each arm. One IV will be used for drawing samples and the other  for the infusion of glucose. During the GGIT, continuous intravenous infusions of  glucose will be given at progressively increasing rates: 1, 2, 3, 4, 5, 6, and 8 kg/min  in six infusion periods of 40-min duration. Blood samples will be collected for  measurements of glucose, insulin, and C-peptide concentrations at fasting and at 30 min  and 40 min into each infusion period. The two values during the last 10 min of each  infusion period will be averaged. The amount of blood taken for this test will 47.5 ml.  Visit 4.Insulin Suppression test, IST 17,18: This test will take approximately 6 hours.  This test is designed to determine whole body insulin sensitivity. Following an  overnight fast, subjects will have an IV placed in each arm. One for collection of blood  and the other for infusion with octreotide (0.27 μg/m2/min), insulin (32 mU/m2/min), and  glucose (267 mg/m2/min) for 180 minutes. During the test, endogenous insulin is  suppressed and all individuals are given the same concentration of insulin, based on  their body surface area. Blood is drawn every 30 minutes for 150 minutes and then at  10-minute intervals from 150 to 180 minutes of the infusion to measure plasma glucose  and insulin concentrations. The mean of the last four values is used as the steady-state  plasma insulin (SSPI) and glucose (SSPG) concentrations for each individual. As SSPI  concentrations are similar in all subjects during the IST, the SSPG concentration  provides a direct measure of the ability of insulin to mediate disposal of an infused  glucose load; the higher the SSPG concentration, the more insulin resistant the  individual. Labs to check kidney and liver function plus a lipid panel and a urine  pregnancy test (if appropriate) will be done at this visit. Blood drawn or IST will be  58.5 ml and 5 ml for SHC labs.  Labs for iPOP will be drawn at this time and additional samples will be obtained for  transcriptome, microbiome, metabolome, and proteome analysis in blood; nasal, tongue,  skin surface swabs; urine; and stool.  The study drug, atorvastatin 40 mg will be given to study participants, once all labs  have been reviewed and participant qualifies.  Visit 5-7: Visits will be every 2 weeks for a total of 10 weeks on study medication  (statin). Participants will be assessed for any side effects or adverse events (AE) on  the statin. Adherence to study medication will be assessed at each visit.  Visit 8: Weight, vital signs, and OGTT described above.  Visit 9: Repeat GGIT as described above.  Visit 10: Repeat IST and iPOP lab testing and samples as described above. At the end of  this visit, the statin will be stopped and the study participant would be scheduled for  4- and 8-week follow up visits.  Visit 11: One month off statin study visit - weight, vital signs, and iPOP laboratory  testing and samples will be done as described above.  Visit 12: Last study visit - weight, vital signs, and iPOP laboratory testing and  samples will be done as described above.  Participants will be asked to fill out questionnaire about her/his physical activity  status, food and eating habits, and stress at the time of each iPOP.  5. STATISTICAL CONSIDERATIONS  Based on our prior work19, we calculated that with 60 subjects, we would be able to detect an  8% change in SSPG concentration and an 8% change in ISRAUC after atorvastatin therapy with  80% power and two-side significance level of 5% using a paired samples t test. Thus, we  estimated needing to enroll 75 subjects with an anticipated a dropout rate of 20%.  Summary statistics will be reported as median (interquartile range) or number (percent) of  participants unless otherwise specified. Shapiro-Wilk tests will be used to assess normality  of data, and variables that are not normally distributed will be log-transformed. Percent  changes in variables will be calculated by the formula: [(end-of study value) - (baseline  value) / baseline value] x 100. Paired samples t tests will be used to compare baseline and  end-of-study means. One sample t tests will be employed to evaluate whether percent changes  in variables are significantly different from zero (no change). Pearson correlation  coefficients will be calculated to determine the strength of association between variables of  interest. Prespecified subgroup analyses will be carried out by stratifying for insulin  resistant versus insulin sensitive subjects. The SSPG concentration median will be used to  define subjects as being insulin resistant or insulin sensitive. Insulin resistant and  insulin sensitive group means will be compared by independent sample t tests and proportions  by chi-square tests or Fisher's exact tests. Statistical analyses will be performed by using  statistical software IBM SPSS version 26.0. Inclusion Criteria:  1. Healthy adults 30 - 70 years old  2. BMI: 20 - 37 kg/m2  3. Without diabetes as defined by fasting plasma glucose <126 mg/dL and not taking  glucose lowering medications  4. Eligible for statin therapy for primary prevention of ASCVD based on LDL-C ≥ 130  mg/dL, > 5% ASCVD risk over 10 years, or hs-CRP ≥ 2.0 mg/L Exclusion Criteria:  1. Younger than 30 or older than 70 years  2. Persons with any significant co-morbidities, such as diabetes (fasting glucose ≥ 126  mg/dL or use of glucose lowering medications), active coronary artery disease, heart  failure, accelerated or malignant hypertension, kidney disease (creatinine ≥ 1.5  mg/dL), liver disease (alanine aminotransferase > 2 times upper limit of normal), or  severe anemia (hematocrit < 30%).  3. Individuals taking any medications for weight loss or known to influence insulin  sensitivity.  4. Pregnant or lactating  5. Women unwilling to use an effective birth control method  6. History of statin intolerance

Rationale: Surgical trauma and post-surgical pain induce a physiological stress response that  can be detrimental to the patient. Non-pharmacological interventions aimed at stress  reduction are known to reduce pain scores and opioid consumption. The effect of these  interventions on the surgical stress response are unknown.  Objective: To assess the effect of a bundle of non-pharmacological interventions implemented  in the post-anesthesia care unit on the total serum cortisol levels after intermediate and  major surgery.  Study design: This is a prospective before-after study. Study population: Patients scheduled  for intermediate or major oncological surgery in a tertiary referral cancer center.  Intervention: The implementation of a bundle of four non-pharmacological interventions aimed  at stress reduction in the post-anesthesia care unit. The bundle consists of: access to  music, aromatherapy, natural images on the walls and ceiling and communication techniques  aimed at reduction of stress and pain.  Main study parameters/endpoints: Serum cortisol levels on the first postoperative day. This protocol is a substudy of a larger observational before-after study that studies the  effects of the planned implementation of a bundle of non-pharmacological interventions in the  post-anesthesia care unit on pain scores, opioid consumption and quality of recovery.  In this current protocol, a subset of 90 surgical patients of a tertiary referral cancer  centre in the Netherlands will be included and will be asked to provide informed consent for  additional blood samples to be drawn to study the effects of the stress-reducing bundle on  biomarkers of the surgical stress response.  45 eligible patients will be approached in the before-arm of the study and 45 will be  included for the after-arm. Inclusion criteria are: planned for intermediate to major  oncological surgery with an expected duration of >120 minutes, without the use of neuraxial  anesthetic techniques. Patients with a planned postoperative ICU-admission will be excluded.  After providing informed consent, they will be asked to complete a Quality of Recovery  (QoR-15) questionnaire prior to surgery. Additional blood will be drawn with their routine  preoperative blood sample on the morning of surgery to determine levels of cortisol,  interleukine-6 (IL-6), glucose, C-reactive protein (CRP) and Neutrophil-Lymphocyte  Ratio(NLR). The same blood sample will be drawn on arrival in the PACU and on the morning of  the first postoperative day. Patients will also be asked to complete the QoR-15 questionnaire  again on the first postoperative day.  The primary outcome will be serum cortisol level on the first postoperative day (as a  biomarker of the surgical stress response). Inclusion Criteria:  -  ASA 1-3  -  scheduled for intermediate to major oncological surgery  -  with a minimum duration of 120 mins Exclusion Criteria:  -  Neuraxial anesthetic technique  -  planned for postoperative ICU admission  -  day case surgery  -  Indication for peri-operative steroids  -  chronic use of steroids  -  Bronchial hyperreactivity

This is a Phase 1 dose-escalation study of PRT3789, a SMARCA2 degrader, in participants with  advanced or metastatic solid tumors with loss of SMARCA4 due to truncating mutation and/or  deletion. The purpose of this study is to evaluate the safety, tolerability, pharmacokinetic  (PK), and pharmacodynamic (PD) of PRT3789, describe any dose limiting toxicities (DLTs),  define the dosing schedule, and to determine the maximum tolerated dose (MTD) and recommended  phase 2 dose (RP2D) to be used in subsequent development of PRT3789. This is an open-label, multi-center, dose-escalation, first in human, Phase 1 study of  PRT3789, a SMARCA2 degrader, evaluating participants with selected advanced or metastatic  solid tumors with loss of SMARCA4 due to truncating mutation and/or deletion. The study will  evaluate escalating doses of PRT3789 until the MTD or RP2D is determined. Taking into account  pharmacokinetic and pharmacodynamic data from the preceding dose levels, the dose may be  escalated until a dose limiting toxicity is identified. Approximately 86 participants will be  enrolled in dose escalation and backfill cohorts. Inclusion Criteria:  -  Willing and able to comply with all scheduled visits, treatment plan, laboratory  tests, lifestyle considerations (including contraception requirements), and other  study procedures  -  Histologically confirmed advanced, recurrent, or metastatic solid tumor malignancy  with loss of SMARCA4 due to truncating mutation and/or deletion by local testing that  have either progress on or ineligible for standard of care therapy  -  Must have measurable or non-measureable (but evaluable) disease  -  Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1  -  Willing to provide either archival or fresh tumor tissue sample  -  Adequate organ function (hematology, renal, and hepatic) Exclusion Criteria:  -  Participants with solid tumors with known concomitant SMARCA2 mutation or loss of  protein expression  -  Clinically significant or uncontrolled cardiac disease, uncontrolled electrolyte  disorders, uncontrolled or symptomatic central nervous system (CNS) metastases or  leptomeningeal disease  -  History of another malignancy within 3 years except for adequately treated basal cell  or squamous cell skin cancer, superficial bladder cancer, prostate intraepithelial  neoplasm, carcinoma in situ of the cervix, or other noninvasive or indolent  malignancies, or malignancies previously treated with curative intent and not on  active therapy or expected to require treatment or recurrence during the study  -  Concurrent treatment with strong or moderate CYP3A4 inhibitor or inducer

The collection of data from the myriad of services described is significantly impacted by NIH  guidelines defining medical research involving humans as well as the recent implementation of  HIPAA constraints which further complicate the conduct of retrospective clinical outcomes  research. Simple case reports or case series analysis now involve IRB participation as well  as voluminous documentation.  The solution to this dilemma lies in developing and promoting secure, confidential  prospective clinical databases for storing clinical data for subsequent retrospective  de-identified inquiry. These databases function in a way analogous to "tissue banks" for  subsequent basic science research. Patients consent to prospective entry of their clinical  information into the database so long as they continue to be a patient with the Department of  Neurological Surgery or the Departments or Divisions in association with the affiliated  programs briefly described above. The consent is obtained during the patient's first  inpatient or outpatient encounter in parallel with the HIPAA consent. It can be withdrawn by  request of the patient at any time, but it does not expire unless the patient withdraws it,  or the patient severs their patient care relationship with UCI Neurosurgery or the affiliated  programs. The database is stored on a separate secure server maintained and backed up by the  UCIMC Information Technology Department. Access to the database is restricted at multiple  levels, with the majority of personnel allowed only limited access for data entry purposes.  Only the database programmer/coordinator, the Department Administrator and the Chairman of  the Department will have unrestricted access to the database. Authority for permission for  levels of security clearance and access to the database, for other individuals, will be  vested in the Chairman of the Department of Neurological Surgery.  A separate IRB proposal will be formulated for individual study related to the acquisition of  data from the de-identified database. Since these future studies will be performed on data  sets derived from the previously consented subjects of this IRB-approved project, the  requirement for additional consent forms are not anticipated. As a result IRB research  proposals utilizing the database can be expedited. Once the specific study is approved, the  investigator(s) are provided with the clinical information from the database in the form of a  de-identified data set. The Department of Neurological Surgery is entering a period of rapid growth accompanied by  significant investment in its infrastructure. The goals of this effort is to re-establish a  full academic mission and for the return of a residency program as part of this paradigm with  the target of initiating the program in three to five years. This rebuilding project will be  based on the pre-existing neurotrauma and critical care program and three new comprehensive  and multidisciplinary clinical programs and medical center product lines. These include  neuro-oncology, operative and non-operative spine services and cerebrovascular services. The  care and treatment of patients with ischemic stroke is a part of the cerebrovascular program.  Aggressive and accelerated clinical outcomes research and rapid peer-review publication is a  mission critical need for successfully applying to re-establish the residency training  program. The collection of this data will also strengthen marketing and will promote the  advancement of the multidisciplinary programs. While the Neurosurgery Department is central  to the multidisciplinary program evolution these affiliated programs and product lines  involve multiple departments. These include: Neurology with the stroke service and neurology  critical care services; Radiology with the neuroradiology and interventional neuroradiology  services; the Hematology/Oncology Services associated with the Chao Family Comprehensive  Cancer Center; Radiation Oncology; Otolaryngology Services; Orthopedic Spine Services; and,  Physiatry with the Physical and Rehabilitative Medicine Services.  MD Analyze is a commercially available relational data base software program designed to  accumulate clinical data for future analysis. It allows the investigators to determine what  clinical data they wish to collect, including, but not limited to history, physical,  laboratory, radiographic, surgical and follow-up information. It can be programmed to allow  data entry from any data collection instrument so desired by the investigators.  Patients treated by the investigators in their practices at UCI will be asked to sign consent  and HIPAA forms making them aware of their rights and protection regarding their health care  information and giving informed consent to collect and analyze their health care data.  Throughout the course of their care they may be asked to complete various surveys or data  collection instruments depending on their diagnosis and treatment. See Appendix A for copies  of the data collection instruments and surveys. The system allows the personal clinical data  to be de-identified (i.e., made anonymous). A full-time data entry clerk will collect and  enter clinical data into the MD Analyze data base. This person will also be asked to search  and retrieve data based on investigators' research questions after their proposals have been  IRB approved. Only the Department Chairman, the Data Base Manager, and the Department  Administrator will have access to personal identification data. This information will not be  available to the investigators. Potential investigators of the data base will have to provide  documentation of IRB approval of their project to the Chair before their requested data set  can be harvested from the data base. The chair will then direct the Data Base Manager to  generate a report of the requested data. The report of de-identified data will then be  securely delivered to the investigator. The Data Base Manager will maintain a file of all  requests for data and a copy of the IRB approval for investigators research and data request.  Minors may be asked to complete surveys and questionnaires appropriated to their reading  level. Patients may withdraw at any time by making a request to their physician investigator  or their staff. Inclusion Criteria:  -  Patient of one of the investigators mentioned in the IRB Protocol Narrative  -  Ability to give informed consent to have health care info collected, stored, analyzed  -  Ability to sign HIPAA form Exclusion Criteria:  -  Nonpatient of one of the investigators in the study  -  Minors under the age of 7  -  Patients without the ability or capacity to give informed consent

Septic shock is a major life-threatening vasodilatory shock. Vasopressor form a crucial  pharmacotherapeutic option and have long been used as the first and foremost recommended  therapy.(1) However, some patients may remain refractory to catecholamine, which is also  known as catecholamine-resistant septic shock.(2, 3) High-dose catecholamine therapy may lead  to potential side effects such as increased myocardial oxygen consumption, lethal arrthymias,  and even the high risk of mortality. (4)Therefore, newer alternatives like dopamine,  dobutamine, somatostatin, and terlipressin are also used.  Cirrhosis is a state of hyperdynamic circulation, which worsens with the onset of infection.  In septic shock, there is relative deficiency of vasopressin. (13) The mortality of septic  shock in these patients still remains extremely high. Terlipressin is a synthetic vasopressin  analogue with greater selectivity for the V1-receptors.(5) In cirrhotics with septic shock,  terlipressin has been used either as a continuous intravenous infusion or as intravenous  boluses. However, at present none of studies reveal which would be a better mode of  administration in cirrhotics with septic shock considering the reversal of hemodynamics and  safety of patients. Methodology:  -  Study population: All the consecutive patients of cirrhosis admitted to Intensive care  unit of Hepatology department of ILBS will be evaluated for inclusion  -  Study design: Prospective open label randomised controlled study -superiority trial. The  study will be conducted in Department of Hepatology ILBS- intensive care unit.  -  Study period: 1 year from ethics approval (Feb 21- Jan 22)  -  Sample size: Assuming that the response rate is 90% in continuous and 80% in bolus ,  with α=5% β=80% and the superiority margin taken as 10%; then we need to enroll 141  cases in each arm, further taking 10% drop out rate, we need to randomise a total of 310  cases (155 in each arm). Randomisation will be done by block randomisation method by  taking block size as 10.  -  Intervention: 250 patients after screening for all exclusion criteria randomised into 2  arms(group-1, Terlipressin bolus arm) and(group-2, Terlipressin continuous infusion arm)  in a ratio 1:1.  -  250 patients after screening for all exclusion criteria randomised into 2 arms(group-1,  Terlipressin bolus arm) and(group-2, Terlipressin continuous infusion arm) in a ratio  1:1.  -  Monitoring and assessment  Both the group will undergo assessment of cardiac function by measuring NT-Pro BNP, Troponin  I, ANP and baseline transthoracic echocardiography (TTE), 30 minutes after the first bolus  dose and after the starting of infusion, lastly at 72 hours.  TTE will be performed to evaluate the cardiac function; Cardiac output (velocity time  integral at aortic flow times the area of left ventricular outflow tract), LV ejection  fraction by modified Simpson's method, LV diastolic function by E/E' measurement, right  ventricular systolic function by fractional area change, tricuspid annular plane systolic  excursion (TAPSE), and flattening of the interventricular septum.  -  USG Doppler will be performed in all the patients to assess the flow in renal, portal,  hepatic veins and also permeability index, and extravascular lung volume.  -  The macro-hemodynamic parameters were MAP, heart rate, cardiac output, SVR index, global  end diastolic volume, extravascular lung water, lung permeability index and hourly urine  output. Global tissue perfusion adequacy and microcirculation assessment was done by  -  1. SVR index = MAP-CVP/CO *80 ( 700 - 1500dynes/sec/cm-5  -  2. Global EDV = combined end diastolic volume of all 4 chambers.  -  3. Lactate of Blood Gas preferably  -  4. Lactate clearance13 (defined by lactate baseline-lactate at time point/baseline  lactate ×100)  -  5. Central venous O2 saturation (SCV02) with a target of SCVO2>70%  -  In all patients, baseline endotoxin activity assay and blood sample will be stored for  looking at the effect of therapy on cytokine profile (TNF alpha, IL6, IFN-gamma, and  ADAMTS and vWillebrand factor).  -  Improvement in Endothelial dysfunction would be assessed by measuring the biomarkers  such as Endotoxin, von willebrand factor and ADAMTS at three times At baseline (Hour 0),  at 30 minutes after Terlipressin dose and at 72 hours.  -  Renal function would be measured by serum Renin, serum cystatin C, urine NGAL,eGFR, and  improvement in AKI stage according to KDIGO criteria or requirement of dialysis.  -  For assessment of impact of coagulation, ROTEM would be performed at respective time.  -  Also the serum level of Noradrenaline and terlipressin will be assessed at starting and  after 72 hours.  STATISTICAL ANALYSIS: Continuous data- Student's t test  -  Non parametric analysis- Mann Whitney test  -  Survival outcome By Kaplan-Meier method curve.  -  For all tests, p≤ 0.05 will be considered statistically significant.  -  Analysis will be performed using SPSS .  -  The analysis will be done with intention to treat and per protocol analysis if  applicable.  - Adverse effects Severity of adverse events (CTACE Grade) GRADE-1  -  Loose motion(2 -3 episodes)  -  Hyponatremia (135-130) GRADE-2  -  Loose motion (4-6 episodes)  -  Abdominal pain  -  Hyponatremia (130-120) GRADE-3  -  Loose motion (> 6)  -  Bacterial infections  -  Chest pain  -  Circulatory overload  -  Hponatremia( <120)  GRADE-4  -  Arrhythmia  -  Myocardial Infarction  -  Mesenteric ischemia  -  Livedo reticularis  -  Respiratory acidosis  -  Hepatic encephalopathy  -  Gastrointestinal bleeding  -  Peripheral cyanosis  -  Lactic acidosis  -  Bradycardia  -  Atrial fibrillation  -  Ventricular tachycardia GRADE-5  -  Death  -  Stopping Rule: Side effects or toxicities that are severe -arrhythmia, AMI,  Cardiomyopathy (defined later) Cyanosis and all orther grade IV adverse effects of  Terlipressin.  -  Suspicion or confirmed bowel ischemia.  -  Patient unwilling for further hospital stay.  -  Study unrelated complication here the drug effects could not be assessed (massive  GI bleed uncontrolled, bowel perforation or any surgical intervention). Inclusion Criteria:  - Cirrhotics including ACLF with septic shock requiring norepinephrine dose >0.5ug/kg/min  to maintain MAP> 65 mm Hg  - An informed consent from the patient or relative Exclusion Criteria:  -  Patients with age less than 18 years or more than 65 years  -  Severe known cardiopulmonary disease (Hypertension, structural or valvular heart  disease, coronary artery disease, arrhythmias)  -  Stroke  -  Peripheral Vascular disease  -  Gut Paralysis  -  Intestinal obstruction  -  Cancer, hepato-cellular carcinoma (HCC), intrahepatic or extrahepatic malignancy  -  Portal vein thrombosis  -  Hepatic vein outflow tract obstruction (HVOTO )  -  Pregnancy  -  Patients with Pa02/FiO2 ratio <150  -  Severe coagulopathy platelets <20,000 and INR > 4  -  Active Bleed (Mucosal or variceal)  -  Patients already on terlipressin in the last 48 hours  -  Extremely moribund patients with an expected life expectancy of less than 24 hours  -  Failure to give informed consent from family members.  -  Patient enrolled in other clinical trials

Phase I: Eligible participants (n=20) will be recruited to participate in a feasibility  evaluation of the client intake module to be developed. Participants will complete pre- and  post-intervention knowledge assessment outcome measures. The gain score, defined as the  difference between the pre-training and post-training score, will be calculated for each  participant. Each participant will spend up to 2 hours interacting with the intervention.  Additionally, an implementation focus group (n=6) of administrators, educators, and key  decision-makers will be conducted to assess the feasibility of implementing the proposed  training suite in their programs.  Phase II: During Phase II, participants (n=100) will complete in two standardized patient  encounters pre- and post-intervention to evaluate the efficacy of the proposed training  suite. Participants assigned to the intervention group will receive 10 hours of training with  the product and will be asked to complete a Training Experience Questionnaire after their  post-intervention standardized patient encounter. Control group participants will receive the  APA guidelines for Psychological Practice with Transgender and Gender Non-Conforming People  for review. Control group participants will submit their notes taken while reviewing the  guidelines. It is expected that the intervention group will show increased knowledge, skill,  awareness, and cultural competency when working with the target population as measured by the  Standardized Patient encounters as rated on a Standardized Patient Checklist. Additionally,  the team anticipates the experimental group participants will rate the training suite as easy  to use, relevant, and realistic. Phase I:  In order to assess feasibility and measure success in development, the team will recruit 20  providers in training from multiple sites around the United States to utilize the Intake  Module to determine if the product changes provider knowledge. SIMmersion and their  collaborators successfully used this methodology in a prior SBIR Fast-Track proposal to train  health care providers in suicide assessment skills (R44 MH114710).  Hypothesis: The investigative team hypothesizes that there will be a positive gain score on  the knowledge assessment for a majority of the participants after interacting with the  training simulation for one hour.  Outcome Data:  Demographics: Participants will complete a demographic questionnaire related to age, sex,  race, ethnicity, area of licensure, years of experience, prior training experience and  experience with TGNC populations.  Usage Data: Each participant will be asked to complete the simulated conversation within the  module a minimum of two times. The program will automatically store their usage data.  Product Evaluation: Upon completion of the post-test knowledge assessment, participants will  be asked to provide feedback related to the usefulness, feasibility, scalability,  appropriateness, ability to practice, and engagement level of the simulation using Likert  scales (0-10) and open-ended questions.  Phase II:  Control Group: Students randomized to the control group will be given an electronic copy of  the Guidelines for Psychological Practice with Transgender and Gender Non-Conforming People  (APA, 2015) and asked to take notes in the pdf document. The amount of time students spend on  the document and note-taking will be recorded and notes will be analyzed for content. As an  incentive, the participants in the control group will be given access to TTACS after they  complete the post-intervention assessment.  Educational Intervention: The educational intervention will be TTACS, the training program  with simulated roleplays. Each participant will be asked to schedule 10 hours of time to  utilize the simulation. In order to ensure all participants adhere to the minimum  intervention requirements, each will be asked to schedule training time with a member of the  research team. Participants will attend an initial training session where each participant  will receive a short orientation about the product and its capabilities. Participants will  attend an initial training session at one of two sites Psychology Department at Towson  University or SIMmersion's office in Columbia, MD based on participant preference. Subsequent  training sessions may be completed at Towson, SIMmersion or can be completed individually.  Participants will receive confirmation emails the day before a scheduled session and a phone  call to reschedule any missed sessions.  While the program will be set up as a ready-to-use training package, prior research efforts  have shown that requiring participants to utilize the training product in a computer lab  provides consistent compliance rates which lead to a more accurate evaluation of the  product's efficacy. However, given the demanding nature of practicing students' schedules,  requiring all intervention usage at our two sites may be difficult for participants. The  research team anticipates that the proposed method will accommodate for participant schedules  while still ensuring intervention compliance.  Demographic Collection: All training participants will complete a questionnaire designed to  gather background information on demographic characteristics and other important  characteristics. Information collected will include age, gender, race, program enrollment,  prior exposure/training in working with TGNC individuals, and current coursework. This data  will permit between-group comparability during subsequent data analysis.  Performance Improvement Assessment Using Standardized Patient Methodology (H1-H4). The skills  test will consist of two Standardized Patient (SP) testing stations, as described above. Each  station is set up in 30-minute units. Prior to counseling each SP, participants will have 5  minutes to review scenario instructions. This will provide background information on the  client's previous encounters with the clinician, if any. Then, the participant will have 25  minutes to work with the SP.  Ten SPs will be recruited and trained by the staff at Towson University and Dr. Mastroleo.  Training will be conducted in 3-hour sessions and include scenario, demonstration role-plays  and/or videotapes, observed script practice sessions, group discussion of the character they  are portraying and the questions that may be asked. They will also be taught how to time and  score (using the checklist) the sessions.Dr. Mastroleo has been training SPs for intervention  trials for the past 10 years and is well equipped to do so for this project.  Methods to Ensure Reliability of Standardized Patient Performance: All SP interactions will  be audio recorded for review and further evaluation. The research team will review the first  5 tapes of each SP and every 5th tape thereafter to ensure the SPs are following the script  and scenario protocol. It is the researchers' experience that 10-20% of SPs are not able to  follow the script despite extensive training. Utilizing this review methodology identifies  these SPs immediately so they can be replaced with SPs that can adhere to the study  protocols.  Training Experience Questionnaire: Upon completion of the post-intervention SP encounters,  each participant in the intervention arm will be asked to complete a Training Experience  Questionnaire (TEQ) which will allow them to evaluate TTACS using a series of 5-point Likert  scale questions and open-ended prompts. The research team anticipates that participants will  indicate agreement or strong agreement on the TEQ that the product is (H5) an acceptable  training tool (i.e., easy-to-use, realistic, relevant) and contributes to their skill  development. Inclusion Criteria: None Exclusion Criteria: None

The goal of this Fast-Track Small Business Innovation Research (SBIR) project is to test the  newly expanded Jaspr2.0, developed to efficiently and reliably aid delivery of recommended  best-practices for the treatment of suicidal ideation in adults, including suicidal  individuals who also misuse alcohol. Jaspr1.0 was developed by the PIs under NIMH SBIR Phase  I and Phase II awards (R43MH108222 & R44MH108222; Dimeff & Jobes). This current proposal will  expand Jaspr content to include content relevant to primary care and brief interventions for  the treatment of suicidal ideation and alcohol misuse. Jaspr2.0 will include techniques for  prevention of suicidal behaviors (ideation, planning, attempts) and death by suicide while  providing support in the moment after discharge via a companion mobile app, Jaspr-at-Home.  Jaspr2.0 will include: psychoeducation, behavioral skills training, crisis stabilization  planning, lethal means management, brief interventions for the treatment of suicidal ideation  and alcohol misuse, and messages of hope, wisdom, and insights from people with lived  experience (PLE).  Investigators will conduct a 12-week randomized controlled clinical trial (N=120) comparing  Jaspr2.0 (n=60) to an active control condition (Virtual Hope Box + electronic wellness  resources brochure; n=60) in adults experiencing suicidal ideation. Participants will be  randomly assigned to condition utilizing a minimization randomization procedure to match  participants across condition on suicide severity, depression severity, and alcohol misuse.  To ensure a sufficient sample of individuals who misuse alcohol, no fewer than 35% (n=42) of  the sample will be comprised of individuals who experience harmful or hazardous levels of  alcohol use. Participants will be assessed at baseline, 4, 8, and 12 weeks. Investigators  will conduct a small 6-week pilot trial (N=20; Jaspr n=15; Active Control n=5) prior to  commencing the full RCT to test both study procedures and Jaspr2.0. Jaspr Health ("Jaspr"; R44MH108222) is a service-ready, commercially viable suicide  prevention platform originally optimized to deliver suicide prevention evidence-based  practices (EBPs) when used by acutely suicidal patients in emergency departments (EDs).  Grounded in Jobes' Collaborative Assessment and Management of Suicidality (CAMS), Jaspr  guides patients in completing a comprehensive suicide risk assessment and lethal means  counseling, builds a crisis stabilization plan, and teaches behavioral skills to reduce  imminent distress; videos of people with lived experience (PLE) offer wisdom and hope for  getting through suicide crises. Information is summarized for the care team to aid in  discharge disposition planning. Jaspr includes a companion app for home use to provide care  transition support post-discharge. Results from a randomized controlled trial (RCT; N=31)  comparing it to Care-as-Usual (CAU) strongly support its feasibility, acceptability, and  effectiveness in increasing use of EBPs, reducing agitation and distress, improving capacity  to cope with suicidal thoughts and improving ED satisfaction. Also, 100% of the 105 acutely  suicidal ED patients who participated in all research phases recommended Jaspr for others in  their situation. Jaspr's careful alignment with healthcare systems' (HCS) ED needs has led to  rapid commercial adoption since completion of the RCT in 2020, with paid pilot tests in five  EDs, and a contract to implement Jaspr in 13 EDs within a large Midwest HCS in 2021.  This 34-month fast track seeks to adapt Jaspr for primary care (Jaspr 2.0) and significantly  expand its use to increase public health impact: (1) focus on those who are experiencing  suicidal ideation only; (2) extend its utility to CAMS treatment; and (3) include an alcohol  module when alcohol use disorder (AUD) is interfering with the ability to address and treat  suicide drivers and/or is exacerbating the patient's primary problems. The CAMS approach will  guide the integration of AUD EBPs. Investigators will design Jaspr for several primary care  provider (PCP) use cases: serving as a real-time tool to guide PCPs in treating suicidal  behaviors, as a treatment adjunct for patients to use on their own as "homework" in between  PCP visits, and as a self-help tool for use during the care transition while waiting for  mental health outpatient services.  Investigators will conduct a 12-week intent-to-treat RCT with 120 suicidal adults 18 years  and older. Participants will again be recruited through Mayo Clinic and social media (to  ensure sufficient participant flow, participant diversity, and participants with AUD).  Participants will be randomly assigned to Jaspr2.0 (n=60) or an active control condition  (n=60) including Virtual Hope Box, a well-regarded suicide prevention self-help app, plus an  electronic wellness resources brochure containing links to health and wellness materials,  psychoeducation about suicide, depression, self-help recovery-focused resources (e.g.,  Alcoholics Anonymous and other 12-Step programs, Moderation Management, etc.), and phone/text  information for the National Suicide Prevention Lifeline. Participants will be assessed at  baseline, 4, 8 and 12 weeks. Primary outcome variables include: suicidal behaviors (ideation,  planning), self-efficacy and coping with suicidal thoughts and distress, and use of  evidence-based strategies to cope with distress (behavioral skills, use of a crisis stability  plan). Secondary outcome variables will include alcohol misuse and suicide attempts  (considered secondary outcome due to the low base rate). App satisfaction and use of  technology outcomes (i.e., degree of usage, features used) will be examined and reported  descriptively.  Investigators hypothesize that in comparison to the active control condition, Jaspr2.0  participants will show significantly better outcomes from baseline to the 4, 8, and 12 week  assessment points such that:  1. Jaspr participants will report significantly greater decreases in suicidal and alcohol  misuse behaviors compared to study controls.  2. Jaspr participants will report significantly greater increases in self-efficacy and  coping with suicidal thoughts and distress, as well as use of suicide prevention  strategies compared to study controls.  3. Jaspr participants will report a higher degree of satisfaction with their respective app  compared to controls with theirs. Inclusion Criteria:  -  18+ years of age  -  English speaking  -  Currently has a primary care provider and sought care from them in the past year  -  Owns and is the primary user of an Android- or Apple-based smartphone with data plan  -  Scores 1 or greater on Item 9 of the Patient Health Questionnaire-9 (PHQ-9)  To ensure a sufficient sample of individuals who misuse alcohol, no fewer than 35% of the  sample will be comprised of individuals who score 8 or more on the Alcohol Use Disorders  Identification Test (AUDIT), indicating a harmful or hazardous level of drinking. Exclusion Criteria:  -  Severe depression (PHQ-9 score of 20 or greater)  -  Alcohol dependence (AUDIT score of 15 or greater)  -  Acutely suicidal (affirms item 5 of the Ask Suicide Screening Questions)  -  Significant drug abuse problems (scores 11 or greater on the Drug Abuse Screening  test)  Individuals who are excluded because of the severity of their depression, suicide acuity,  and/or degree of substance use disorder will be provided with resources (i.e., National  Suicide Prevention Lifeline, this study's crisis hotline number (Boys Town), SAMHSA's  National Helpline) and encouraged to reach out to their primary care provider.

This research trial studies how well biospecimen collection works in identifying genetic  changes in patients with breast, prostate, colorectal, liver, or kidney cancer or multiple  myeloma undergoing surgery. Studying samples collected during surgery may add to the  understanding of cancer by looking for the genetic changes that cause early cancer onset in  people of certain racial and ethnic groups. PRIMARY OBJECTIVE:  I. To acquire tissue and blood, and other biospecimens for research purposes during  procedures for clinical care to accelerate our understanding of the molecular basis of early  onset cancers occurring in racial and/or ethnic minority populations through the application  of genome analysis technologies, including large- scale genome sequencing and clinical data  analysis.  OUTLINE:  Patients undergo collection of tumor tissue during surgery. Patients also undergo blood  samples. Samples collected may undergo genetic analysis including whole exome sequencing.  After completion of study, patients are followed for up at 6 and 12 months. Inclusion Criteria:  -  Patients with either:  -  Histologically confirmed invasive carcinoma or multiple myeloma OR  -  Clinical diagnosis of carcinoma or multiple myeloma OR  -  Suspected clinical diagnosis of multiple myeloma  -  Patients with one of following tumor types and age ranges:  -  Breast cancer diagnosis at ages 18-45  -  Colon cancer diagnosis at ages 18-55  -  Kidney cancer at diagnosis at ages 18-50 (American Indian or Alaska Native [AIAN]  and non-Hispanic Whites [NHW] only)  -  Liver cancer diagnosis at ages 18-55  -  Prostate cancer diagnosis at ages 18-55  -  Multiple myeloma diagnosis at ages 18-50  -  Patients whose tumor specimen was collected or will be collected during one of the  following routine procedures:  -  Surgery to remove cancer OR  -  Routine biopsy procedures performed to confirm a histologic diagnosis OR  -  Routine biopsy procedure performed to obtain additional tumor material for  routine prognostic or predictive biomarkers OR  -  Routine procedure to place a vascular access device prior for systemic therapy  -  Patients who have received no therapy for their cancer other than surgery,  irrespective of stage  -  Collection of specimens from living patients:  -  Ability to understand and willingness to sign a written informed consent document  indicating their willingness to have their tissue or biologic fluid specimens  used for research as outlined in this protocol  -  Collection of specimens from deceased patients:  -  Banked tissue samples and/or banked biologic fluid specimens of deceased patients  may be used as long as all samples or specimens are properly de- identified prior  to submission  -  Sites must use the Central Institutional Review Board for the National Cancer  Institute (NCI CIRB). Exclusion Criteria:  -  Patients who do not meet criteria for an early onset malignancy  -  Prior systemic therapy or radiation therapy for their malignancy  -  Tumor does not meet quality metrics  -  Patient refused consent for use of tissue for research activities included in the  Early Onset Malignancies Initiative  -  A diagnosis of a synchronous invasive malignancy  -  Patients with a history of invasive cancer or hematologic malignancy in preceding 5  years

A prospective, single-arm,mutil-center study to assess the efficacy and safety of Surufatinib  combined with Toripalimab in Recurrent or Metastatic Nasopharyngeal Carcinoma. This study adopt Simon's two-stage Optimal designs method based on the primary endpoint of  objective response rates. 4 patients were planned for the first stage. If one or more  responses were observed, an additional 8 patients were to be accrued for a total of 12  patients. If 4 or more of the 12 patients achieved an objective response, then this study was  designated worthy of additional investigation.Considering a 10% abscission rate, a total of  14 patients were included.  Surufatinib（250mg) will be orally administered within 1 hour after breakfast once a day (QD)  , Toripalimab was administered intravenously at a fixed dose of 240 mg, and the infusion time  was 60 ± 5 min, once every 21 days. The cumulative longest medication period is 2 years.  Until disease progression, death, intolerable toxicity or other protocol specified  end-of-treatment criteria is met . Inclusion Criteria:  1. Provision of written Informed Consent Form (ICF) prior to any study specific  procedures;  2. Male and Female aged between 18 and 75 years are eligible;  3. Histologically or cytologically confirmed that Recurrent or Metastatic Nasopharyngeal  Carcinoma.  4. Patients must have received at least one standard platinum-based systemic chemotherapy  regimen for the treatment of recurrent or metastatic NPC;Or the insensitivity or  intolerance to platinum when the patient has previously received radical therapy;  5. Not suitable for local treatment (no radiotherapy or surgery);  6. Presence of at least one measurable target lesion for further evaluation according to  RECIST criteria;  7. Eastern Cooperative Oncology Group (ECOG) performance status 0-2;  8. Screening laboratory values must meet the following criteria (within past 14 days):  -  neutrophils ≥1.5×109/L ;  -  platelets ≥100×109/L；  -  hemoglobin ≥ 10 g/dL;  -  total bilirubin ≤ 1.5 x upper limit of normal (ULN); aspartic transaminase (AST)  and alanine transaminase (ALT) ≤ 2.5 x ULN without, and ≤ 5 x ULN with hepatic  metastasis; serum creatinine ≤1.5╳ULN;  9. Ability to follow the program;  10. Toxic side effects of any previous chemotherapy have returned to less than or equal to  NCI CTCAE1 level or baseline;  11. Predicted survival >3 months;  12. Males or female of childbearing potential must: agree to use using a reliable form of  contraception (eg, oral contraceptives, intrauterine device, control sex desire,  double barrier method of condom and spermicidal) during the treatment period and for  at least 6 months after the last dose of study drug. Exclusion Criteria:  1. The pathological type was neuroendocrine or small cell carcinoma;  2. Evidence with active CNS disease or previous brain metastases;  3. Prior received anti-tumor monoclonal antibodies or other investigational drugs within  the first 4 weeks of enrollment;Previous treatment with other anti-PD-1 antibodies or  other treatments targeting PD-1 / PD-L1.  4. Prior treatment with Surufatinib,or other antiangiogenic drugs were used ;  5. Patients were on immunosuppressive or systemic hormone therapy (doses greater than  10mg/day prednisone or other equivalent hormone) for immunosuppressive purposes and  were still on it within 2 weeks prior to enrolment;  6. The patient has any active autoimmune disease or a history of autoimmune disease;  7. Have clinical cardiac symptoms or diseases that are not well controlled;  8. Patients with congenital or acquired immune deficiency;  9. Chemotherapy, targeted therapy and radiotherapy were received within 2 weeks before  enrollment;  10. Patients who had a history of gastrointestinal perforation or had undergone major  surgery 4 weeks before enrollment;  11. During the first 6 months of enrollment, there were arterial/venous thrombosis events,  such as non-cardiovascular and cerebrovascular (including temporary ischemic attack),  deep vein thrombosis (except for venous thrombosis caused by intravenous  catheterization during pre-chemotherapy, which was determined by the investigators to  be cured), and pulmonary embolism;  12. Patients with abnormal coagulation function (International normalized ratio (INR) >1.5  or partially activated prothrombin time (APTT) >1.5×ULN), bleeding tendency (such as  active ulcer lesions in the stomach, occlusive blood in the stool (++), melenia and/or  hematemesis and hemoptysis within 3 months) or lesions close to large vessels.The  lesions involved in the skin or mucosal cavity are at risk of rupture;  13. Hypertension that cannot be controlled by medication;  14. Routine urine indicated more than 2+ urine protein or 24 hours urine protein >150mg/L;  15. Calibration of QT interval > 470MSEC;If the patient has an extended QT interval, but  the investigator's study evaluates the prolonged period as due to a pacemaker (and no  other cardiac abnormality), it is up to the investigator to determine whether the  patient is eligible for the study;  16. Had other malignant tumors in the past 5 years (except for basal cell carcinoma or  squamous cell carcinoma, cervical carcinoma in situ that have been effectively  controlled);  17. Known to be allergic to drug ingredients;  18. Patients at risk of massive bleeding in the nasopharynx or deep ulcers in the  nasopharynx.

This is a a prospective cohort study. According to the inclusion criteria, volunteers were  recruited from patients undergoing total knee arthroplasty. The patients are devided into two  groups: the conventional TKA,the computer-assisted surgery(CAS) using Brainlab Knee 3  system.The differences of postoperative alignment,operative time,blood loss will be studied  between the two groups.Clinical and functional evaluation using the scoring system of  HSS(Hospital for Special Surgery) score, Western Ontario and McMaster University  osteoarthritis index (WOMAC), Forgotten joint score(FJS-12) will be compared between the 2  groups,after surgery, and at the follow-up of 3 months、6 months and 12 months. According to the inclusion criteria, patients receiving primary total knee arthroplasty were  recruited and divided into two groups after doctor-patient joint decision: the traditional  group underwent prosthesis placement using traditional intramedullary positioning method;The  navigation group performed surgery using the Brainlab Knee 3 navigation system.Informed  consent was signed after grouping. All patients were operated by the same knee prosthesis  system. Both groups underwent the same procedures such as the installation of the soft tissue  adjustment, prosthesis placement, wound closure and so on.All patients were given the same  perioperative treatment, such as hemostasis, anti-infection and analgesia, and routine  postoperative rehabilitation exercises. The full length anteroposterior and lateral  radiographs of both lower extremities in weight-bearing position were taken preoperatively  and one week postoperatively.The differences of postoperative alignment,operative time,blood  loss will be studied between the two groups.Clinical and functional evaluation using the  scoring system of HSS(Hospital for Special Surgery) score, Western Ontario and McMaster  University osteoarthritis index (WOMAC), Forgotten joint score(FJS-12) will be compared  between the 2 groups,after surgery, and at the follow-up of 3 months、6 months and 12 months. Inclusion Criteria:  1. Patients with knee osteoarthritis who underwent primary TKA;  2. Informed consent has been signed and medical records are complete;  3. No severe varus or valgus deformity of the knee (< 20°). Exclusion Criteria:  1. Patients undergoing revision knee replacement;  2. patients with rheumatoid arthritis and secondary knee osteoarthritis;  3. Patients with severe valgus deformity(≥ 20°);  4. Taking anticoagulant drugs for a long time in the past, or suffering from the  following diseases: Renal insufficiency, liver insufficiency, severe heart disease (or  coronary stent implantation within the last 12 months), severe respiratory disease,  history of deep vein thrombosis in the lower extremities or a high risk of thrombosis  (hereditary/acquired thrombosis), coagulation dysfunction, stroke, and malignancy

The purpose of this research is to test the effectiveness of an experimental drug combination  for people with metastatic castration-resistant prostate cancer (mCRPC).  The names of the study drugs involved in this study are:  -  Telaglenastat (CB-839)  -  Talazoparib This research study is a Phase II clinical trial, researching the effectiveness of the  combination of telaglenastat and talazoparib in participants with metastatic  castration-resistant prostate cancer (mCRPC).  The U.S. Food and Drug Administration (FDA) has not approved telaglenastat or the combination  of telaglenastat and talazoparib as a treatment for any disease.  The FDA has not approved talazoparib for metastatic castration-resistant prostate cancer  (mCRPC) but it has been approved for other uses.  Telaglenastat is a drug designed to stop cancer growth by blocking glutaminase activity.  Glutaminase is an enzyme in the body that is overproduced by some cancers and can fuel cancer  growth. Telaglenastat can lower or block glutaminase and may slow the growth or spread of  some cancers.  Talazoparib is a drug that interferes with the repair activity of proteins called poly  adenosine diphosphate ribose polymerases (PARP), which are found in normal and cancer cells  and are involved in the repair of DNA - the genetic material found in every cell. This  interference may lead to increased amounts of DNA defects and cancer cell death which may  help to slow the growth of cancer cells.  The research study procedures include screening for eligibility and study treatment including  evaluations and follow up visits.  There are different points in this study in which participation will start. The first group  of participants will receive the combination of telaglenastat and talazoparib for the  entirety of the study. If telaglenastat plus talazoparib is beneficial to the first group  this will lead to the enrollment of the next group, since telaglenastat as a single drug has  not been evaluated in prostate cancer. The next group will receive telaglenastat alone with  the addition of talazoparib if the disease gets worse.  It is expected that about 30 people will take part in this research study. Inclusion Criteria:  -  Participants must have histologically or cytologically confirmed diagnosis  adenocarcinoma of the prostate.  -  Prostate cancer must be metastatic as confirmed by CT, PET scan, and/or bone scan.  -  Prior biopsy of metastatic lesion (bone, lymph node, or visceral metastasis) with  sufficient tissue for molecular analysis, or consent for a fresh biopsy for molecular  analysis  -  Participants must have tested negative for homologous recombination (HR) mutations  (including known deleterious mutations in BRCA1, BRCA2, or ATM) on a blood-based or  tissue-based assay  -  History of bilateral orchiectomies or ongoing GnRH agonist or antagonist  -  Castration-resistant disease based on progression per Prostate Cancer Working Group  2.21  -  Prior treatment for metastatic prostate cancer with docetaxel and either abiraterone  acetate or enzalutamide, OR ineligible for or declines treatment with docetaxel,  abiraterone acetate, or enzalutamide.  -  Adequate renal function with a serum creatinine ≤ 2.0 mg/dL or an estimated or  calculated creatinine clearance of > 50 mL/min (calculated using the formula of  Cockcroft and Gault)  -  Adequate hepatic function with total bilirubin ≤ 1.5x the upper limit of normal (ULN)  and ALT and AST less than 3x the ULN.  -  Adequate hematological function with ANC ≥ 1500/mm3, hemoglobin ≥ 9.0 g/dL, and  platelet count ≥ 100,000/mm3  -  Age ≥ 18 years  -  ECOG performance status of 0 or 1  -  Ability to understand and the willingness to sign a written informed consent document  -  Patients/participants with female partners of childbearing potential are eligible to  participate if they agree to ONE of the following for the duration of the study:  -  Are abstinent from penile-vaginal intercourse as their usual and preferred  lifestyle (abstinent on a long-term and persistent basis) and agree to remain  abstinent for duration of the study.  -  Agree to use a male condom and have their partner use a contraceptive method with  a failure rate of <1% per year (intrauterine device or hormonal implant).  -  Patients/participants must refrain from donating sperm for the duration of the study.  -  Patients/participants with a pregnant or breastfeeding partner must agree to remain  abstinent from penile-vaginal intercourse or use a male condom during each episode of  penile penetration for the duration of the study. Exclusion Criteria:  -  Participants who have received more than two prior chemotherapy regimens for  metastatic castration-resistant prostate cancer.  -  Participants who have any previous treatment with PARP inhibitors  -  Participants who are receiving any other investigational agents.  -  Participants who have received radiation therapy within 2 weeks or radionuclide  treatment within 6 weeks prior to registration on this study  -  Participants with known brain metastases should be excluded from this clinical trial  because of their poor prognosis and because they often develop progressive neurologic  dysfunction that would confound the evaluation of neurologic and other adverse events.  -  History of allergic reactions attributed to compounds of similar chemical or biologic  composition to telaglenastat or talazoparib  -  Concurrent use of moderate or strong CYP3A4 inducers or inhibitors, which could affect  talazoparib plasma concentrations  -  Uncontrolled intercurrent illness including, but not limited to, ongoing or active  infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac  arrhythmia, or psychiatric illness/social situations that would limit compliance with  study requirements.  -  Patients known to be positive for Human Immunodeficiency Virus (HIV), Hepatitis B, or  Hepatitis C.

We aimed to introduce a new modified suture bridge technique and report the clinical outcomes  and radiological assessments of modified suture bridge technique for medium rotator cuff  tears. Purpose: We aimed to introduce a new modified suture bridge technique and report the clinical  outcomes and radiological assessments of modified suture bridge technique for medium rotator  cuff tears.  Methods: We prospectively followed 50 consecutive patients with medium rotator cuff tears  treated with the modified suture bridge (MSB) or traditional suture bridge technique (TSB)  from December 2018 and December 2019. On the basis of preoperative findings and MRI  performance, 26 patients underwent MSB repair whereas 24 underwent TSB repair. Range of  shoulder motion, visual analog scale score (VAS score), University of California-Los Angeles  score (UCLA score), Constant-Murley shoulder score (Constant score), American Shoulder and  Elbow Surgeons score (ASES score) were assessed. Magnetic resonance imaging were performed  preoperatively and at 12 months postoperatively. Inclusion Criteria:  -  (1) full-thickness medium tears (1-3cm) of primary supraspinatus (SSP) tendon was  identified on preoperative MRI and intraoperative arthroscopy, (2) undesirable  conservative treatment for 3 months, (3)completed follow-up of 12 months  postoperatively and patients who adhered to the rehabilitation plan. Exclusion Criteria:  -  (1) previous shoulder surgery, (2) Other pathological changes that would need to be  addressed at the time of arthroscopic surgery, such as rotator cuff tear involving the  subscapular (SSC) tendon，biceps tendon injury, (3) failure to follow our postoperative  rehabilitation protocol and patients without regular follow-up.

Although the notions that kidney transplantation is the treatment of choice for patients with  end-stage renal disease and that simultaneous kidney and pancreas transplant is the only  treatment able to restore euglycemia in patients with type 1 diabetes and selected patients  with type 2 diabetes, are now consolidated, rates of transplantation remain low among  potential candidates with high levels of preformed anti-HLA antibodies. Most of the data  comes from the experience in kidney transplant but can be easily translated to pancreas  transplant.  Approximately 30% of patients on the transplant waiting list have evidence of sensitization  in the form of alloantibodies, generated from exposure to previous transplants, blood  transfusions, pregnancy, or other events. The presence of a panel-reactive antibody level of  at least 80% (i.e. a high level of sensitization) creates difficulty in finding matched  kidneys from compatible donors, leading to lower rates of transplantation in highly  sensitized candidates compared to non-sensitized; the longer waiting times translates in an  increased mortality rate. Despite the development of desensitization strategies and the  advancement in immunosuppression protocols, it is apparent that transplanting these patients  carries an increased risk of acute antibody mediated rejection; 25%-50% of transplants will  have an early acute antibody mediated rejection . Most of these rejections can be  successfully treated, but a high rate of transplant glomerulopathy and chronic antibody  mediated rejection (AMR) leading to accelerated allograft failure is common. Although the notions that kidney transplantation is the treatment of choice for patients with  end-stage renal disease and that simultaneous kidney and pancreas transplant is the only  treatment able to restore euglycemia in patients with type 1 diabetes and selected patients  with type 2 diabetes, are now consolidated, rates of transplantation remain low among  potential candidates with high levels of preformed anti-HLA antibodies. Most of the data  comes from the experience in kidney transplant but can be easily translated to pancreas  transplant.  Approximately 30% of patients on the transplant waiting list have evidence of sensitization  in the form of alloantibodies, generated from exposure to previous transplants, blood  transfusions, pregnancy, or other events. The presence of a panel-reactive antibody level of  at least 80% (i.e. a high level of sensitization) creates difficulty in finding matched  kidneys from compatible donors, leading to lower rates of transplantation in highly  sensitized candidates compared to non-sensitized; the longer waiting times translates in an  increased mortality rate. Despite the development of desensitization strategies and the  advancement in immunosuppression protocols, it is apparent that transplanting these patients  carries an increased risk of acute antibody mediated rejection; 25%-50% of transplants will  have an early acute antibody mediated rejection . Most of these rejections can be  successfully treated, but a high rate of transplant glomerulopathy and chronic antibody  mediated rejection (AMR) leading to accelerated allograft failure is common.  This protocol has been designed to demonstrate the feasibility and efficacy of spleen  transplant as a desensitization strategy for highly sensitized patients, potential candidates  of kidney or simultaneous kidney pancreas transplant with (positive cross-match by flow  cytometry (T or B) or B positive standard cross-match). After obtaining surgical and research  consent at a pre-transplant clinic visit, patients will be receiving spleen transplant  followed by spleen removal and kidney or simultaneous kidney pancreas transplant. Duration of  the subject participation will begin upon consent and will last for one year after the  surgery.  Incidence of treated acute rejection (humoral or cellulo-mediated) within the first year  (defined as biopsy proven or clinically indicated) will be determined. Graft and patient  survival will be monitored and compared with a cohort of highly sensitized patients with  similar immunological characteristics, treated with our standard protocol. DSA levels and  post-transplant cross-match will be determined. Inclusion Criteria:  -  Subjects must give written informed consent, and  -  Subject is ≥ 18 years of age, and  -  Subject is eligible for a kidney or simulateous kidney pancreas transplant, and  -  Subjects are highly sensitized (cPRA 98-100%), and  -  Subjects have a positive T flow crossmatch Exclusion Criteria:  -  Severe cardiac disease not amenable to intervention  -  Clinical significant systemic infection within 30 days prior to transplant  -  Life expectancy < 1 Year  -  Positive pregnancy test performed < 1 week prior to enrollment or intention to plan a  pregnancy in the following year  -  Current drug or alcohol abuse  -  Uncontrolled, severe psychiatric illness  -  Combined transplantation of kidney and other organs

The study aimed to determine the effects of different birthing balls used at the first stage  of childbirth on birth outcomes and maternal satisfaction. Randomized controlled,  single-blind clinical study included a total of 180 pregnant women. The study included 3  groups (A: routine hospital care, B: spherical birthing ball, C: peanut ball). Especially  spherical birthing ball, were effective in reducing labor pain and facilitating faster rate  of descent of the fetal head, and they increased maternal satisfaction. The study aimed to determine the effects of different birthing balls used at the first stage  of childbirth on birth outcomes and maternal satisfaction. Randomized controlled,  single-blind clinical study included a total of 180 pregnant women. The study included 3  groups (A: routine hospital care, B: spherical birthing ball, C: peanut ball). Especially  spherical birthing ball, were effective in reducing labor pain and facilitating faster rate  of descent of the fetal head, and they increased maternal satisfaction.  IMPACT STATEMENT What is already known on this subject? Labor pain and outcomes occurring  during labor are known and expected situation. Some non-pharmacological methods are applied  to ensure that birth is easy and maternal satisfaction is high.  What the results of this study add? There is no studies using the peanut ball and the  spherical birth ball together. In our study, it was found that both balls are effective, but  the spherical birth ball is more significant.  What the implications are of these findings for clinical practice and/or further research?  Our study suggested that the spherical birth ball had effective on birth outcomes. Future  studies should be performed to investigate the effects of birth balls in the postpartum  period, breastfeeding or prenatal period. Inclusion Criteria:  -  primiparous  -  admitted to the delivery room for vaginal delivery  -  38-40 week  -  being in the latent phase of labor  -  having no obstetric risks Exclusion Criteria:  -  undergo caesarean sections for various reasons  -  having obstetric risks

This phase II trial studies cediranib maleate in combination with olaparib in treating  patients with solid tumors that have spread to other parts of the body (advanced/metastatic)  or cannot be removed by surgery (unresectable), including breast cancer, non-small cell lung  cancer, small cell lung cancer, and pancreatic cancer. Cediranib maleate and olaparib may  stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.  Cediranib maleate may also block the flow of oxygen to the tumor, and may help make the tumor  more sensitive to olaparib. PRIMARY OBJECTIVE:  I. To determine the objective response rate (ORR) of cediranib (cediranib maleate) plus  olaparib in combination in patients with advanced or metastatic solid tumors of the following  tumor types: non-small cell lung cancer (NSCLC), triple negative breast cancer (TNBC),  pancreatic ductal adenocarcinoma (PDAC), and small cell lung cancer (SCLC).  SECONDARY OBJECTIVES:  I. To assess the safety and tolerability of oral administration of cediranib in combination  with olaparib in patients with select advanced solid tumors.  II. To estimate progression free survival (PFS) in each tumor cohort.  EXPLORATORY OBJECTIVES:  I. To estimate the prevalence of the mutations of deoxyribonucleic acid (DNA) repair genes in  tumors using the BROCA panel and to correlate tumor regression with mutations status.  (Integrated) II. To evaluate changes in tumor hypoxia on cediranib treatment compared to  baseline by [F-18] fluoromisonidazole (FMISO) positron emission tomography/computed  tomography (PET/CT) in patients with NSCLC.  III. To evaluate levels of angiogenesis/inflammatory markers including VEGF at baseline and  on treatment.  IV. To evaluate levels of circulating tumor deoxyribonucleic acid (ctDNA) at baseline and on  treatment.  OUTLINE:  Patients receive cediranib maleate orally (PO) once daily (QD) on day 1. Patients undergoing  FMISO scan also receive olaparib PO twice daily (BID) beginning the day after the second  FMISO scan and the rest of the patients receive olaparib PO BID beginning day 4 of cycle 1.  Cycles repeat every 28 days (35 days for cycle 1) in the absence of disease progression or  unacceptable toxicity.  After completion of study treatment, patients are followed up for 4 weeks and then every 4  weeks thereafter. Inclusion Criteria:  -  Patients must have histologically confirmed, metastatic or unresectable malignancy of  the following types: (a) non-small cell lung cancer (NSCLC), (b) triple-negative  breast cancer (TNBC; defined by estrogen receptor [ER] < 1%, progesterone receptor  [PR] < 1% and HER2 1+ or less by immunohistochemistry [IHC]; if HER-2 expression is  2+, a negative fluorescence in situ hybridization [FISH] testing is required) (c)  pancreatic adenocarcinoma (PDAC), or (d) small cell lung cancer (SCLC)  -  Must have received at least one line of standard systemic treatment for locally  advanced or metastatic disease setting of the respective tumor type; for NSCLC, it is  either PD-1/PD-L1 inhibitor, or platinum-containing chemotherapy, or an EGFR tyrosine  kinase inhibitor or an ALK inhibitor if sensitizing mutation present; TNBC:  platinum-containing chemotherapy; PDAC: fluorouracil (5-FU-), gemcitabine-, or  taxane-containing chemotherapy either with or without radiation therapy; SCLC:  platinum-containing chemotherapy for limited or extensive stage disease  -  Patients must have measurable disease by Response Evaluation Criteria in Solid Tumors  (RECIST) version (v)1.1  -  Toxicities of prior therapy (except alopecia) should be resolved to =< grade 1 as per  National Cancer Institute (NCI)-Common Terminology Criteria for Adverse Events (CTCAE)  version (v)5.0; patients with long-standing stable grade 2 neuropathy or prior grade 2  treatment-related hypothyroidism requiring treatment, provided free T4 within normal  range, may be considered eligible after discussion with the study principal  investigator (PI)  -  Eastern Cooperative Oncology Group (ECOG) performance status 0, 1 or 2 (Karnofsky >=  50%)  -  Life expectancy of >= 4 months  -  Leukocytes >= 3,000/mcL  -  Absolute neutrophil count >= 1,500/mcL  -  Platelets >= 100,000/mcL  -  Hemoglobin > 9 g/dL  -  Total bilirubin =< 1.5 x the institutional upper limit of normal (ULN)  -  Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase  [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT])  =< 2.5 x institutional ULN  -  Creatinine =< 1.5 x ULN OR  -  Creatinine clearance >= 45 mL/min/1.73 m^2 for patients with creatinine levels above  institutional normal; the creatinine clearance is calculated using Cockcroft-Gault  formula  -  A urine protein: creatinine ratio of < 1 or < 1 g protein on 24-hour urine collection  -  International normalized ration (INR) within 1.25 x ULN institutional limits, except  where a lupus anti-coagulant has been confirmed  -  Activated partial thromboplastin time (aPTT) within 1.25 x ULN institutional limits,  except where a lupus anti-coagulant has been confirmed  -  Patients must be able to tolerate oral medications and not have gastrointestinal  illnesses that would preclude absorption of cediranib or olaparib  -  Adequately controlled thyroid function defined by free T4 within normal range, with no  symptoms of thyroid dysfunction  -  Adequately controlled blood pressure (BP) < 140 mmHg (systolic) and < 90 mmHg  (diastolic) taken in the clinic setting by a medical professional within 2 weeks prior  to starting study; patients with hypertension may be managed with up to a maximum of 3  antihypertensive medications; patients who are on 3 antihypertensive medications are  highly recommended to be followed by a cardiologist or blood pressure specialist for  management of BP while on protocol  -  Patients who have the following risk factors are considered to be at increased risk  for cardiac toxicities, and must have documented left ventricular ejection fraction  (LVEF) by echocardiogram greater than institution's lower limit of normal (or 55% if  threshold for normal not otherwise specified by institutional guidelines) obtained  within 3 months  -  Prior treatment with anthracyclines  -  Prior treatment with trastuzumab  -  A New York Heart Association (NYHA) classification of II controlled with  treatment  -  Prior central thoracic radiation therapy (RT), including RT to the heart  -  History of myocardial infarction within 12 months (patients with history of  myocardial infarction within 6 months are excluded from the study)  -  The effects of cediranib and olaparib 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; should a woman become pregnant or  suspect she is pregnant while she or her partner is participating in this study, she  should inform her treating physician immediately; men treated or enrolled on this  protocol must also agree to use adequate contraception prior to the study, for the  duration of study participation, and for 4 months after completion of cediranib and  olaparib administration  -  Ability to understand and the willingness to sign a written informed consent document  -  Age >= 18 years. There is no dosing or adverse event data currently available on the  use of cediranib or olaparib in patients < 18 years of age, thus excluding them from  enrollment Exclusion Criteria:  -  Patients who have had chemotherapy or RT within 3 weeks prior to start of the study  agents, or those who have not recovered from adverse events due to agents administered  more than 3 weeks earlier  -  Patients should not have received any other investigational agents within the past 4  weeks  -  Patients with untreated brain metastases, spinal cord compression, or evidence of  symptomatic brain metastases or leptomeningeal disease as noted on computed tomography  (CT) or magnetic resonance imaging (MRI) scans should be excluded from this clinical  trial, since neurologic dysfunction may confound the evaluation of neurologic and  other adverse events (AEs); screening brain MRI (or CT if MRI contraindicated) will be  required for patients with recurrent NSCLC, TNBC, or SCLC; brain MRI (or CT if MRI  contraindicated) is required for PDAC if clinically suspected by patient's symptoms or  neurological exam; should patient found to have brain metastasis, treatment of brain  metastasis must precede the participation in this study; for patients with known and  treated brain metastases is allowed in this study if they fulfill the following  criteria:  -  The lesions have improved or remained stable radiographically and clinically for  at least 6 weeks after completion of brain irradiation or stereotactic brain  radiosurgery and off steroids for at least 6 weeks  -  Patients who have received prior inhibitor of VEGF signaling and a poly (ADP-ribose)  polymerases (PARP) inhibitor administered in combination; unless administered in  combination, patients who received a prior PARP inhibitor or a prior VEGF-signaling  inhibitor agent are allowed after discussing with the PI  -  History of allergic reactions attributed to compounds of similar chemical or biologic  composition to cediranib or olaparib  -  Participants receiving any medications or substances that are strong inhibitors or  inducers of cytochrome P450, family 3, subfamily A, polypeptide 4 (CYP3A4) are  ineligible; dihydropyridine calcium-channel blockers are permitted for management of  hypertension  -  Current use of natural herbal products or other complementary alternative medications  (CAM) or "folk remedies"  -  Patients with concomitant or prior invasive malignancies within the past 3 years;  subjects with treated limited stage basal cell or squamous cell carcinoma of the skin  or carcinoma in situ of the breast or cervix are eligible  -  Uncontrolled intercurrent illness including, but not limited to, ongoing or active  infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac  arrhythmia, or psychiatric illness/social situations that would limit compliance with  study requirements  -  History of myocardial infarction within 6 months prior to registration  -  History of stroke or transient ischemic attack within 6 months prior to registration  -  NYHA classification of III or IV  -  Current cardiac arrhythmia requiring concurrent use of anti-arrhythmic drugs  -  History of hypertensive crisis or hypertensive encephalopathy within 3 years prior to  registration  -  Clinically significant peripheral vascular disease or abdominal aortic aneurysm (> 5  cm) or aortic dissection; if known history of abdominal aortic aneurysm with >= 4 cm  in diameter, all of the following must be met:  -  An ultrasound (US) within the last 6 months prior to registration will be  required to document that it is =< 5 cm  -  Patient must be asymptomatic from the aneurysm  -  Blood pressure must be well controlled as defined in this protocol  -  A major surgical procedure, open biopsy, or significant traumatic injury within 28  days prior to starting cediranib (percutaneous/endobronchial biopsies are allowed)  -  History of bowel obstruction within 1 month prior to starting study drugs  -  History of hemoptysis or any significant bleeding within the last 1 month prior to  enrollment  -  Presence of cavitation of central pulmonary lesion  -  History of abdominal fistula, intra-abdominal abscess, or gastrointestinal perforation  within the 3 months prior to enrollment  -  Patients may not have current dependency on intravenous (IV) hydration or total  parenteral nutrition (TPN)  -  Patients may not have evidence of coagulopathy or bleeding diathesis; therapeutic  anticoagulation for prior thromboembolic events is permitted; the clinical indication  for therapeutic anticoagulation must be clearly documented prior to enrollment and  must be discussed with the P.I.; given the increases risk of serious bleeding from  cediranib, patients who are on greater than or equal to 2 anti-thrombotic agents,  including but not limited to anti-platelet agents (non-steroidal anti-inflammatory  drugs [NSAIDs]/aspirin, clopidogrel), heparin, low molecular weight heparin (LMWH),  warfarin, and a direct thrombin inhibitor, will be excluded  -  Patients may not have features suggestive of myelodysplastic syndrome (MDS) or acute  myelogenous leukemia (AML) on peripheral blood smear or bone marrow biopsy, if  clinically indicated  -  Pregnant women are excluded from this study because olaparib and cediranib have the  potential for teratogenic or abortifacient effects; due to the fact that there is an  unknown but potential risk for adverse events in nursing infants secondary to  treatment of the mother with olaparib and cediranib, breastfeeding should be  discontinued if the mother is treated with cediranib and olaparib  -  Human immunodeficiency virus (HIV)-positive patients on combination antiretroviral  therapy are ineligible because of the potential for pharmacokinetic interactions with  cediranib or olaparib; appropriate studies will be undertaken in patients receiving  combination antiretroviral therapy when indicated; HIV-positive patients with  undetectable viral loads and CD4 counts > 300, and not on any antiretroviral therapy  may be allowed after discussing with the principle investigator  -  Any condition that, in the opinion of the treating investigator would interfere with  evaluation of the investigational product or interpretation of subject safety or study  results

This is a pilot study to assess the ability of [F-18]fluciclovine to differentiate  pseudoprogression from progression in participants after therapy, at imaging time points  within the 12 week interval post chemoradiation. [F-18]fluciclovine. PET will be obtained at  the time point in the 12 week interval in which MRI demonstrates increase in enhancing volume  with the differential diagnosis of pseudoprogression versus tumor progression. At the same  time point (at least 6 hours after [F-18]fluciclovine or up to 3 days) F-18 FDG will also be  performed consistent with standard clinical practice. The verification of pseudoprogression  versus tumor progression will be determined by the regression of enhancing lesion on  subsequent MRI imaging obtained as part of standard care. In this pilot study the investigators propose to image 10 participants who have been  previously diagnosed by resection or biopsy with grade 3 or 4 glioma.  All glioma cases undergoing resection at UPMC are evaluated by immunohistochemistry for  mutations in p53, nuclear localization of ATRX, and the presence of IDH1R132H mutation as  part of standard neuropathologic integrated diagnosis using the WHO 2016 diagnostic criteria.  All glioma cases resected at UPMC undergo genetic profiling using next generation sequencing.  MRI imaging will be obtained as part of standard clinical care. The MRI sequences include T1  pre and post contrast, T2 FLAIR, DWI, ADC and perfusion sequences using the imaging algorithm  for evaluating treatment response in glioma treatment trials. Radiogenomic analysis will be  performed using the MRI imaging sequences obtained as standard clinical care. Inclusion Criteria:  -  1. Age ≥ 18 years old.  2. Been previously diagnosed by resection or biopsy with grade 3 or 4 glioma.  3. Agree to use adequate contraception as indicated in this protocol.  4. Consent to PET scanning and receipt of one injection of 18F-fluciclovine.  5. Able to comply with study procedures.  6. Able to give written consent.  7. Subject has had a standard of care, diagnostic MRI study which was indeterminate  due to the inability to differentiate pseudoprogression versus tumor progression. Exclusion Criteria:  -  1. Are a pregnant or breastfeeding female.  2. Are participating in a clinical trial of another unlicensed product.  3. Are undergoing 18F-fluciclovine PET for reason(s) other than newly diagnosed or  recurrent glioma.  4. Have a hypersensitivity to 18F-fluciclovine.  5. Have acute renal failure or moderate/severe renal impairment, according to local  clinical guidelines.  6. Have a non-MRI compatible implantable device or another contraindication for MRI  scan.  7. Are deemed ineligible to participate for other reasons by an investigator.

This is a pilot, cross-sectional, sample collection study to characterize the immune response  and intestinal microorganisms in people with and without COVID-19 antibodies and helminth  infection. This is a pilot, cross-sectional, sample collection study to characterize the immune response  and intestinal microbiota in people with and without SARS-CoV-1 antibodies and helminth  infection.  A target sample size of 1500 participants aged 5 years or older will undergo a one-time blood  and stool collection for SARS-CoV-2 antibody testing, diagnosis of parasitic infections, and  experimental studies including transcriptomics (RNA) and microbiome (intestinal  microorganisms) characterization. Participants willing to take part in the study will be  selected from households in the Tiruvallur district, Tamil Nadu, India. Individual study  participation involves a single study visit. Participants will be informed of the results of  clinical testing and will be referred for medical care as appropriate. Inclusion Criteria:  -  Able to provide informed consent. Exclusion Criteria:  -  Poor venous access precluding venipuncture.  -  History of any illness or condition which, in the investigator's judgment, may  substantially increase the risk associated with the participant's participation in the  protocol, or compromise the scientific objectives.  Participants may be co-enrolled in other studies; however study staff should be notified of  co-enrollment.

The purpose of pilot study is to test the feasibility of nurse initiated post-operative  bilateral auricular acupressure as an adjunct to medication for post-operative pain  management. Postoperative pain management has become an area of concern over the last decade due to the  opioid epidemic and concerns related to their use as the primary pain management strategy.  Joint Commission requires that hospitals have additional pain non-pharmacologic pain  management tools at their disposal to an effort decrease the reliance on opioids. Acupuncture  and acupressure have been used for centuries in the management of a variety of disorders  including pain. Unlike acupuncture, acupressure can be easily applied with limited training  and is within the scope of practice for nurses, according to the North Carolina Board of  Nursing. Thus evidence based non-pharmacologic strategies that can be deployed by nursing are  of benefit to hospital organizations. Inclusion Criteria:  -  Adults 18-80 admitted for knee or hip arthroplasty  -  Pre-surgery morphine equivalent < 50  -  American Society of Anaesthesiologists (ASA) score < 3 Exclusion Criteria:  -  Participants with a history of skin disease (psoriasis), adhesive allergy, history of  delirium, or cognitive impairment

This study will examine the hypothesis that in obese asthmatics; treatment with NOx + CLA is  well tolerated, safe and will increase eNO while reducing airway oxidative stress. Allied  with this, the investigators will define whether supplementing with this bioactive mediator  modifies the airway microbiome, and reduces airway inflammation. Obesity is an asthma comorbidity associated with increased severity, poor control, reduced  steroid responsiveness and greater exacerbation and healthcare utilization rates. These  associations are not explained by having a greater degree of Th-2 inflammation. Rather, the  obese asthma phenotype defined in several cluster studies, has paradoxically reduced levels  of Th-2 biomarkers, including sputum eosinophils and exhaled nitric oxide (NO). The  investigators previous research has shown that the inverse relation between increased body  mass index (BMI) and reduced exhaled NO, may be explained by a metabolic imbalance  characterized by lower L-arginine and greater asymmetric di-methyl arginine (ADMA) levels.  Having a low L-arginine/ADMA ratio has been shown to inhibit and uncouple all isoforms of  nitric oxidase synthase (NOS), thereby reducing NO bioavailability and promoting oxidative  stress through enhanced superoxide production. In obese asthmatics, this imbalance not only  correlates with exhaled NO, but also with lower FEV1% and poorer asthma-related quality of  life. Yet the effect of obesity in asthma is unlikely to be solely dependent on a single  mechanism. Other factors, such as increased Th1 and Th-17-mediated inflammation have been  shown to occur in human and animal models. Given all of these potential avenues, it is  imperative that an intervention is sufficiently pleiotropic that can, in addition to  restoring airway NO levels, also reduce other obesity-related non-Th2 mechanism of  inflammation. The investigators hypothesize that treatment with conjugated linolenic acid  (CLA) + nitrate and nitrite (together known as NOx), will restore NO airway bioavailability,  reduce oxidative stress and improve airway inflammation in obese asthmatics. To test this  hypothesis, the investigators propose a phase II pilot study in which obese asthmatics with  metabolic syndrome, will be treated orally with CLA+NOx for 8 weeks, in an open label study  design to assess pre to post-intervention changes in airway and systemic biomarkers, and to  determine the effects on lung function and bronchial hyperresponsiveness. Participants will  undergo a pre and post intervention bronchoscopy. The results obtained from this project will  be greatly informative to our understanding of the obese - asthma pathophysiology and for the  development of clinical trials to determine the potential benefit of this intervention in  improving health outcomes. Inclusion Criteria:  -  Adequate completion of informed consent process with written documentation  -  Male and female patients, ≥ 18 - 65 yrs old  -  Diagnosis of asthma: based on previous physician diagnosis and either baseline  pre-bronchodilator FEV1 50% or greater predicted with a 12% or greater bronchodilator  response to 4 puffs of albuterol or PC20 methacholine (16 mg) if no BD response.If the  subject is not currently on an ICS/ ICS LABA, PC20 should be < 8 mg, if no BD  response. Spirometry results within the prior 24 months located in the subject's  medical records can be used to determine eligibility, if available.  -  All racial/ethnic backgrounds with a diagnosis of asthma for ≥6 months  -  Smoking history ≤10 pack years and no smoking in the last year  -  BMI ≥ 30  -  If subject is on ICS or ICS/LABA therapy- 30 days on a stable dose (up to 1,000 mcg  daily fluticasone equivalent)  -  Asthma diagnosed at age 9 or later Exclusion Criteria:  -  Respiratory tract infection within the last 4 weeks  -  Oral or systemic CS burst within the last 4 weeks  -  Asthma-related hospitalization within the last 2 months  -  Asthma-related ER visit within the previous 4 weeks  -  Significant or uncontrolled concomitant medical illness including (but not limited to)  heart disease, cancer, diabetes  -  Chronic renal failure (creatinine > 2.0) at screening (Associated with higher ADMA  levels)  -  Current statins use (statins lower ADMA levels), patients may stop and re-enroll after  2 weeks of stopping statins  -  Positive pregnancy test  -  Intolerance or allergy to the intervention drugs  -  Current or recent (within 30 days) in an investigational treatment study.  -  Unable or unlikely to complete study assessments or the study intervention (i.e.  bronchoscopy) poses undue risk to patient in the opinion of the Investigator.  -  Any kind of oral nitrates such as nitroglycerin or already taking supplements  -  History of ICU admission/intubation due to asthma in the past year;  -  More than three systemic corticosteroid requiring asthma exacerbations in the past  year  -  Systemic steroid dependent asthma (no daily oral steroids- short term therapy for  asthma exacerbation is permitted)  -  Use of mouthwash containing chlorhexidine (lowers NO) within 1 week prior to screening  and throughout the study  -  Untreated sleep apnea  -  Hgb A1C ≥7  -  Daily use of PPI's (Proton Pump Inhibitor) or H2 Blockers for GERD (it is permitted to  take on an occasional basis- no more than 1x per week. If participants wash out of  these meds for 1 week, they can enroll)  -  Use of biologics for asthma/allergies unless there is a 4 month washout prior to  enrollment (the washout for biologics is done for clinical reasons and not  specifically for inclusion for the study).  -  Drug and/or alcohol abuse for ≥1 year  -  Breastfeeding  -  Any other condition and/or situation that causes the investigator to deem a subject  unsuitable for the study (e.g. due to expected study medication non-compliance,  inability to medically tolerate the study procedures, or a subject's unwillingness to  comply with study-related procedures.

The purpose of this study is to explore the outcomes, tolerability and safety of 2 different  doses of oral pantoprazole (full healing dose, half healing dose), assigned based upon  weight, for the maintenance of healing of erosive esophagitis in pediatric participants aged  1 to 17 years with endoscopically-confirmed, healed erosive esophagitis. Explore the outcomes, tolerability and safety of 2 different doses of oral pantoprazole (full  healing dose, half healing dose), assigned based upon weight, for the maintenance of healing  of erosive esophagitis in pediatric participants aged 1 to 17 years with  endoscopically-confirmed, healed erosive esophagitis. Inclusion Criteria:  -  Participants must have a documented erosive lesion with an Los Angeles (LA) Grade of A  to D prior to starting Proton Pump Inhibitor treatment:  -  Capable of giving signed informed consent/assent  -  Willingness and ability of the participant or parent/legal guardian to complete the  eDiary  -  Willing and able to comply with all scheduled visits, treatment plan, laboratory  tests, lifestyle considerations, and other study procedures, including the use of the  eDiary.  -  Male and female participants aged 1 to 17 years.  -  Minimum body weight 7 kilogram and weight at least at the 5th percentile per the  Center for Disease Control standard age and weight chart, for the participant's age.  -  To be considered a female of non childbearing potential, the participant must meet at  least 1 of the following criteria :  -  Premenarchal: The investigator (or other appropriate staff) must discuss the  participant's premenarchal status with the participant and parent/legal guardian at  office visits and during telephone contacts, as participants who achieve menarche  during the study would no longer be considered "female participants of non  childbearing potential" and must comply with the protocol requirements applicable to  women of childbearing potential. Exclusion Criteria:  -  Previous administration of an investigational drug or vaccine within 30 days (or as  determined by the local requirement) or 5 half-lives preceding the first dose of study  intervention used in this study (whichever is longer).  -  Children that may be at high risk from procedural sedation should be carefully  evaluated. Participants with a history of complications during prior procedural  sedation  -  History or presence of upper gastrointestinal anatomic or motor disorders  -  Family history of malignant hyperthermia  -  Known hypersensitivity to any Proton Pump Inhibitor, including pantoprazole or to any  substituted benzimidazole or to any of the excipients.  -  Any disorder requiring chronic (daily) use of warfarin, heparin, other anticoagulants,  methotrexate, atazanavir or nelfinavir, clopidogrel, or potent inhibitors or inducers  of CYP2C19 (eg, phenytoin, sulfamethoxazole, valproic acid, carbamazepine, and  griseofulvin).  -  Serum creatine kinase levels >3 x upper limit of normal.  -  Known history of human immunodeficiency virus or clinical manifestations of acquired  immune deficiency syndrome.  -  Active malignancy of any type, or history of a malignancy. Participants with a history  of malignancies that have been surgically removed or eradicated by irradiation or  chemotherapy and who have no evidence of recurrence for at least 5 years before  Screening are acceptable.  -  Diagnosed as having or has received treatment for esophageal, gastric, pyloric  channel, or duodenal ulceration within 30 days before the Screening visit.  -  Alanine aminotransferase or blood urea nitrogen >2.0 upper limit of normal or  estimated creatinine >1.5 X upper limit of normal for age or any other laboratory  abnormality considered by the Investigator to be clinically significant within 14 days  before the Baseline Visit (Day 1).  -  Other acute or chronic medical or psychiatric condition including recent (within the  past year) or active suicidal ideation or behavior or laboratory abnormality that may  increase the risk associated with study participation or study intervention  administration or may interfere with the interpretation of study results and, in the  judgment of the investigator, would make the participant inappropriate for entry into  this study.  -  Has, in the Investigator's opinion, a serious chronic condition (eg, diabetes,  epilepsy), which is either not stable or not well controlled and may interfere with  the conduct of the study.  -  Has any condition possibly affecting drug absorption (eg, gastrectomy).  Prior or Concomitant Therapy:  -  Frequent, repeated use of oral or parenteral glucocorticoids (eg, prednisone,  prednisolone, dexamethasone). Steroid inhalers and topical steroids may be used.  -  Pregnant female participants; breastfeeding female participants.  -  Is unwilling or unable to comply with the Lifestyle Considerations section

Blood flow restrictive (BFR) therapy following MPFL or ACL reconstruction rehabilitation.  Specific Aim 1: Test whether maintaining BFR cuff inflation or deflating between exercises  results in greater quadriceps strength and functional outcomes after MPFL or ACL  reconstruction.  Hypothesis 1: Subjects in the deflate BFR protocol group will have significantly greater  quadriceps strength, symmetric leg symmetry index on a battery of functional tests and PROs  as compared to the non-deflate group.  Specific Aim 2: Compare whether maintaining BFR cuff inflation or deflating between exercises  results in reduced pain, improved exercise tolerance, and patient-reports outcomes (PRO)  after MPFL or ACL reconstruction.  Hypothesis 2: Subjects in the deflated BFR protocol group will report significantly less pain  and greater exercise tolerance during exercise with significantly improved knee related PRO  scores. Subjects will be aged 13-40 male or female patient following MPFL or ACL reconstruction.  Baseline Assessment at PT Evaluation will included knee AROM and AAROM Heel slide with strap,  Knee edema measured in cm difference Involved to Non-involved at supra and mid patellar  levels, subjects ability to SLR Yes/No in brace, Patient reported outcome measure (PRO's) to  include LEFS, Brief Resiliency scale, MPFL - Norwich Patellar instability, ACL 2000 IKDC  Subjective Knee Evaluation Form questionnaires. Pain assessment to include current, minimal  and maximal pain levels past 24 hours.  Patient are randomized into 1 of 2 groups: Group 1 will deflate between BFR exercises, Group  2 will not deflate between BFR exercises. Both groups will receive the same standard care  same during their first 2 weeks of post-op rehabilitation. BFR will be added to their  rehabilitation care starting at week 3 for 2x/week x 10. There are 4 core BFR exercises that  will be progressed every 2 weeks.  Final Assessment- Strength and Functional Testing at 24th visit or 12 weeks post-op (if  missed appointments) to include bilateral Knee AROM and edema assessments, PRO's: LEFS, Brief  Resiliency scale, MPFL Norwich Patellar instability, ACL 2000 IKDC Subjective Knee Evaluation  Form, Functional assessment to include for involved adn uninvolved leg: Isometric Quad  strength measurement at 90 degrees of knee flexion, Isometric Hip Abduction strength  measurement, Y balance maximum anterior reach, Max reps 6" Forward step-down, max core  strength assessments, and ability in-line jog. Inclusion Criteria:  Post operative Medial Patellar Femoral Ligament or Anterior Cruciate Ligament  Reconstruction. Exclusion Criteria:  -  Had any other previous surgeries or conditions that might affect your gait prior to  injury and 1 year removed from a prior ACL or MPFL reconstruction.  -  Have any current lower extremity condition other than MPFL or ACL reconstruction which  might affect your gait  -  Have a diminished capacity to provide informed consent  -  Are diabetic or have uncontrolled hypertension  -  Have recent inflammation, bleeding disorders, active bleeding or infection within the  lower limbs.  -  You are taking warfarin/Coumadin, clopidogrel/Plavix, Rivaroxaban/Xarelto,  Dabigatran/Pradaxa, apixaban/Eliquis, deoxidant/Savaysa, betrixaban, or any other  anti-coagulants that may cause excess bleeding.  -  Have any implanted medical device  -  Have a history of deep vein thrombosis, vascular graft, varicose veins, and/or sickle  cell anemia  -  Are or suspect you are Pregnant  -  You are not be able to attend regular physical therapy or study visits

Functional near infrared spectroscopy (fNIRS) offers a cheap and reliable tool to investigate  prefrontal brain activation in the healthy and diseased human brain. As such, fNIRS bears  great potential as a diagnostic tool for clinical practice. Research indicates that fNIRS,  together with a relatively simple task to activate the prefrontal cortex, the so-called  verbal fluency task (VFT), elucidates prefrontal dysfunction in major depressive disorder  (MDD). This finding can potentially serve as an imaging marker for disease pathology, even  when depressive symptoms are absent. Indeed, recent research also suggests prefrontal  dysfunction in fully remitted MDD (rMDD). Prefrontal haemodynamic responses may therefore  serve as a trait marker for MDD vulnerability.  This study aims to investigate the haemodynamic response in rMDD, healthy participants with  increased MDD risk (HCr; having a 1st-degree relative with MDD), and low-risk healthy  participants (HCnr; having no 1st-degree relatives with MDD) using fNIRS. The investigators  hypothesize lower prefrontal reactivity in HCr compared to HCnr, and lowest prefrontal  reactivity in rMDD compared to HCnr.  This study has the potential to elucidate the neuronal underpinnings of depression  vulnerability in the absence of symptoms that are sometimes considered a confounding factor  when it comes to studying the biological encoding of depression. Healthy participants with a high risk of MDD (HCr), healthy participants with a low risk of  MDD (HCnr) and rMDD participants will be included in this study.  Prefrontal haemodynamic response will be measured in all participants during the verbal  fluency test (VFT) using 52 channels fNIRS. The VFT involves two neural conditions, one  positive condition, and one negative condition.  Both the neuroimage change and the behavioral outcomes of VFT will be compared within-group  and among groups. The correlation between the neuroimage change and the behavioral outcomes  will be analyzed as well. Inclusion Criteria:  -  Mini-mental state examination (MMSE) > 24 Exclusion Criteria:  -  Current diagnosis of psychiatric disorders, such as depression, anxiety,  schizophrenia, or autism  -  current or past diagnosis of neurological disorders, such as head injuries, strokes,  encephalitis, epilepsy, Parkinson's, or Alzheimer's

Dental caries is one of the most prevalent chronic diseases in people worldwide. Traditional  clinical treatment of dental decay has developed on the basis of the removal of carious  tissues with high-speed handpieces and slow-rotating instruments, inducing pain, disturbing  sounds, and vibrations. In addition, this method comprises the tooth structure by removing  both "caries-affected dentin" and "caries-infected dentin". The use of the chemo-mechanical  caries removal (CMCR) method is one of the main implementations of the minimal intervention  dentistry idea accepted in the last ten years. It includes the selective removal of  "caries-infected dentin" while preserving the healthy "caries-affected dentin" that has the  ability to remineralize. The CMCR method differs from the traditional surgical method in that  it selectively removes carious dentin. Therefore, it is less destructive and less painful,  thereby promoting a positive attitude towards visiting dentists. A novel agent for the CMCR  method named "BRIX3000®" by the laboratory Brix Medical Science has been released onto the  dental market in 2016. It is a papain-based gel derived from latex and fruits of green papaya  (Carica Papaya) that works as a chemical debridement with a unique technology called  Encapsulating Buffer Emulsion (EPE). Investigations are required to evaluate and compare the  outcomes of two CMCR agents, "BRIX3000®" and "Carie-CareTM," versus the traditional surgical  methods. Therefore, the present study aims to perform a clinical and microbiological  evaluation of caries removal using "BRIX3000®" and "Carie-CareTM" versus the traditional  surgical methods in primary molars among children in Jeddah city, Saudi Arabia. Dental caries is one of the most prevalent chronic diseases in people worldwide. It results  in localized dissolution and destruction of the calcified tooth tissues. The destruction of  the dental structure does not occur as a result of a localized accumulation of bacteria, but  rather as a result of an invasive and infectious process caused by the interaction of several  interconnected factors. These factors make dental caries a great challenge for the dentist,  as they seek an efficient means to control it. Carious dentin consists of two distinct  layers: an outer "caries-infected dentin" and an inner "caries-affected". The  "caries-affected" dentin is described as demineralized inter-tubular dentin, crystal  deposition in dentinal tubules, and a lesser amount of destructed collagen matrix with no  bacterial invasion. On the contrary, the "caries-infected" dentin displays deformation of the  microstructure of the dentinal tubules and permanently damaged collagen fibers with  significant penetration of the bacteria. Thus, the "caries-infected" dentin has to be removed  only during caries removal. Traditional clinical treatment of dental decay has developed on  the basis of the removal of carious tissues with high-speed handpieces and slow-rotating  instruments, inducing pain, disturbing sounds, and vibrations. In addition, this method  comprises the tooth structure by removing both "caries-affected dentin" and "caries-infected  dentin". The concept of minimal intervention dentistry (e.g., air abrasion, laser,  chemo-mechanical caries removal (CMCR) agents) includes the selective removal of  caries-infected dentin while preserving the healthy caries-affected dentin that has the  ability to remineralize. It is less destructive and less painful, thereby promoting a  positive attitude towards visiting dentists among children. Brix Medical Science in 2016  released a new CMCR agent named "BRIX3000®". It is an enzymatic gel for non-traumatic caries  removal known with exclusive technology as "Encapsulating Buffer Emulsion" (EPE) that is  claimed to have superior characteristics for caries removal compared to previous products  available in the dental market. There are a few studies present in the literature, most of  them published in non-English language versions, evaluating the clinical and laboratory  properties of "BRIX3000®". Therefore, investigations were required to evaluate and compare  the outcomes of "BRIX3000®" versus the previous CMCR agent, "Carie-CareTM" and the  traditional surgical methods. This study was carried out at King Abdulaziz Dental University  Hospital (KADUH) and the Microbiology Research Laboratory in the Faculty of Pharmacy, King  Abdulaziz University, Jeddah, Saudi Arabia to evaluate the efficacy, efficiency, and pain  experienced by children with the use of the CMCR agents "BRIX3000®" and "Carie-CareTM" versus  the traditional surgical method in primary molars. The study was approved by the "Research  Ethics committee" at the Faculty of Dentistry, King Abdulaziz University (KAU) under approval  number 107-06-19. Informed written consent will be signed by the parents/guardians of the  children after explaining it to them. The study sample will be consisted of healthy and  cooperative children aged 4 to 9 years old with bilateral open occlusal carious lesions in  primary molars who will be seen as outpatients at KADUH's Department of Pediatric Dentistry  from October 2019 to December 2020.The sample size was measured using G power analysis for  calculating an estimated sample size. The final sample will be consisted of 60 children aged  4-9 years with 30 pairs of matched contralateral open occlusal carious lesions in primary  molars meeting the inclusion criteria. They will be randomly allocated to either group (1) or  group (2). In group 1, 30 children with 60 primary molars will be subjected to caries removal  by the CMCR method "BRIX3000®" (the experimental group) on one molar (n = 30) and the  traditional surgical method (the control group) on the contralateral molar (n = 30). In group  2, 30 children with 60 primary molars will be subjected to caries removal by the CMCR method  "Carie-CareTM" (the experimental group) on one molar (n = 30) and the traditional surgical  method (the control group) on the contralateral molar (n = 30). The block randomization  method (a block of the two contralateral teeth) will be used to make sure that each side was  treated evenly by both methods. The statistical assessment will be carried out using the  Statistical Package for Social Sciences (SPSS, V.20, IBM, NY, USA). A significance level of  5% was utilized for all analyses. Inclusion Criteria:  -  Healthy and cooperative patients of age group 4-9 years.  -  Primary first/second molars with open occlusal carious lesion having moderated depth  and clinically visible brownish color softened dentin.  -  No clinical signs or symptoms of pulp degeneration, such as tenderness to percussion  and history of sinus tracts or swelling. Intraoral periapical radiographs with lesions  having radiolucency extending into, but only confined to dentin. Exclusion Criteria:  -  Patients with any major and minor systemic illness.  -  Uncooperative patients that necessitate pharmacological dental treatment.  -  Primary molars with mobile teeth, arrested caries, restored teeth, non-vital teeth, no  carious lesion, presence of developmental defects and non-restorable teeth.  -  Patients on any antibiotic regimen either on the day of treatment or for at least 2  weeks prior to the study.  -  Patients allergic to Latex.  -  Radiographic evidence of external or internal root resorption, furcal or periapical  radiolucency.  -  Primary molars with more than half of the root length resorbed.  -  Children who did not attend and complete the second session of treatment.  -  Not approving to sign the consent.

The objective of this study is to develop, describe in detail and validate a feasible, cheap  and convenient non-invasive sham acupuncture technique in order to use safely and repeatedly  in future studies. Additionally, the reactions of the volunteers to sham needles in different  positions and in different parts of the body will be investigated. Following the Second World War, the evidence based research is the keystone of modern  medicine applications. Randomized, placebo controlled and double/triple blinded clinical  studies are the sine qua non of evidence based medicine. As a matter of course acupuncture  which was defined as traditional and the main outcome was the clinical effects throughout the  centuries, had its share form the tremendous evolution. For the past decades, studies on  acupuncture are designed and prosecuted on the basis of randomized and placebo controlled  trials.  In clinical trials for invasive modalities, placebo is the procedure that mimics the original  procedure in order to provide objective comparison. These procedures are called as sham  techniques and in acupuncture sham techniques are divided into two categories as invasive  sham procedures and non-invasive sham procedures. Non-invasive sham is a technique that is  designed to create a minor sensory stimulation in the absence of skin penetration using a  placebo needle or any device imitating needle. In acupuncture practice it is a fact that sham  procedures are non-inert and even can exert high therapeutic effect. Consequently, the main  concern regarding the randomized controlled trials on acupuncture is that false negative  rates might be misleadingly higher than acceptable values. The clinical therapeutic effects  of non-invasive techniques are attributed to the activation of physiologic endogen systems  due to the belief that acupuncture was applied although it was only sham. Non-invasive  techniques need to be used in clinical trials designed to discriminate this mentioned effect  from the point-specific effects of real acupuncture and non-specific effects obtained by skin  penetration in invasive sham techniques.  The fact that sham techniques used in clinical studies are far from standardization  inevitably increase the false negativity rates. In fact there are various techniques about  non-invasive sham acupuncture. Blunted needles or plastic guide tube, nail, pencil point  probe or even wooden skewers were used. Techniques are not described most of the time and  majority of the studies lack standardization and validation of the non-invasive sham  technique that is used. There are standard Park and Steinberger needles which were developed  privately for non-invasive sham procedures. The advantage these latter needles is that the  patient cannot see the application of the needle. Otherwise as in all non-invasive sham  technique the needles do not penetrate the skin, the patient does not get the de chi  sensation and the stimulation of the needles is not possible. Inclusion Criteria:  -  The healthy attendants of patients referred to General Surgery outpatient clinic Exclusion Criteria:  -  presence of any diagnosed disease  -  on any regular medication  -  skin reaction on the area of planned acupuncture administration  -  neurologic sequela

Overall frame: The overall or "parent" DRAW-project is a large-scale project run in Denmark  that aims to provide substantial level 1A evidence-data related to the question: Does  rehabilitation after total hip and knee replacements work? In the DRAW project, the authors  challenge the belief that physical rehabilitation is clinically important - and surely better  than "no physical rehabilitation". To challenge this belief thoroughly, the DRAW project  holds many individual work packages centered around the same question. These work packages  will be conducted in collaboration with municipality rehabilitation centers in Denmark so  that specific usual care strategies are reflected in the different trials and local clinical  relevance is as well as implementation potential are increased. The DRAW2-trial is a pragmatic, randomised controlled trial that aims to replicate the  DRAW1-trial findings (clinicaltrials.gov: NCT03750448, trial protocol:  https://f1000research.com/articles/10-146). Based on stakeholder input from Municipality  Rehabilitation Bornholm, the DRAW1-trial was designed as a superiority trial to test the  hypothesis that physical rehabilitation (telerehabilitation and home-based rehabilitation) is  superior to no physical rehabilitation in a mixed population of patients after total hip and  knee arthroplasty (THA and TKA, respectively). After DRAW1-trial inclusion was completed and  the target sample size reached, an opportunity to continue the trial presented because  additional funding was obtained. At the same time, Municipality Rehabilitation Bornholm asked  for stratified data (THA/TKA) that could help guide their decision concerning a potential  purchase of telerehabilitation equipment (more details on stakeholder input can be found in  the trial protocol, https://f1000research.com/articles/10-146). To meet this new research  objective of stratified analysis for THA and TKA, it was advised from the local ethical  committee that a new and almost identical trial was registered, which would allow for a  doubling of the sample simple size, so that adequately powered stratified analyses could be  made. This new trial is named the DRAW2-trial.  The DRAW2-trial will adhere to the published DRAW1-trial protocol  (https://f1000research.com/articles/10-146) and only small logistic modifications to trial  procedures have been made. Because some of the DRAW1-trial participants felt overwhelmed by  the amount of information they received during the first and only study introduction (usually  takes place 5-7 days after surgery), the study introduction in the DRAW2-trial can be divided  into two separate consultations a few days apart whenever deemed appropriate by the  consulting physiotherapist. The DRAW2 trial will be reported and published independently,  including the same outcomes and outcome hierarchy as the DRAW1-trial. As such, it will be an  independent replication trial.  Research plan  While the DRAW2-trial will focus on replication of the DRAW-1 trial findings, the opportunity  to run a replication trial at the same trial site with little delay between the two trials  will also enable us to address the questions outlined below, by subsequent pooling of data  from the two trials.  Question 1: Is physical rehabilitation superior to no physical rehabilitation after THA and  TKA using two usual care strategies in Denmark (stratified analyses THA vs. TKA by pooling  DRAW1 and 2 trial data)?  Question 2: Is home-based rehabilitation as good as home-based telerehabilitation in a mixed  population of THA and TKA using two usual care strategies in Denmark (equivalence analysis by  pooling DRAW1 and 2 trial data)?  Question 3: Is physical rehabilitation superior to no physical rehabilitation after THA in  general (using DRAW1 and 2 THA trial data in an ongoing living systematic review?  (https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=203574).  Question 3: Is physical rehabilitation superior to no physical rehabilitation after TKA in  general (using DRAW1 and 2 TKA trial data in an ongoing living systematic review?  (https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42018094785). Inclusion Criteria:  Patients having had primary, unilateral THA or TKA due to osteoarthritis. Patients being  referred to receive postoperative rehabilitation at our institution.  Patients being able to speak, read and understand Danish language. Patients aged ≥ 18  years. Exclusion Criteria:  Patients not able to comply with exercise instructions. Patients who are discharged to a  nursing-home facility or receiving in-home rehabilitation by home care.

The purpose of this study is to determine whether recording heart sounds with an acoustic  stethoscope, combined with artificial intelligence (computer information), will show similar  abnormalities to an echocardiogram or cardiac catheterization. In the current study the plan is to recruit 400 patients who have been referred to the  echocardiogram laboratory for routine clinically indicated echocardiography, or to the  cardiac catheterization laboratory for routine clinically indicated catheterization  procedures. Individuals with normal heart structure and sounds, isolated aortic stenosis (of  varying severity), and isolated mitral regurgitation (of varying severity) will be included,  while excluding individuals who have multiple valve involvements or combined valve  pathologies. Each patient will have baseline testing using the ©CompuSteth device, which will  be used to auscultate and record each patient's heart sounds at the bedside prior to the  index echocardiogram or cardiac catheterization procedure. This process will take less than  10 minutes and is outlined below. Patients will then proceed with their clinically indicated  echocardiograms or cardiac catheterization procedures.  Amongst the first 200 study participants, the results of the echocardiograms and invasive  cardiac catheterization procedures will be used to train the ©VoqX device to identify normal  heart and to screen and grade for various cardiac structural pathologies, aortic stenosis,  and mitral regurgitation, diagnosed by gold-standard testing. Subsequently, after the ©VoqX  device has been trained how to characterize and identify sounds that correspond to various  structural cardiac pathologies, the next step is to prospectively 'test' how well the ©VoqX  device is able to screen normal heart from cardiac pathologies, such as aortic stenosis, and  mitral regurgitation, and identify the severity of the valve disorder in the subsequent 200  participants of the study. This will be done by comparing the results obtained from  auscultation with the ©VoqX device against the results obtained from gold-standard testing  with echocardiography or invasive cardiac catheterization. Inclusion Criteria:  -  Aged 18 years of age or older.  -  Referred to the echocardiogram laboratory for routine clinically indicated  echocardiography, or to the cardiac catheterization laboratory for routine clinically  indicated catheterization procedures  -  Individuals with normal heart sounds, isolated aortic stenosis (any degree of  severity), or isolated mitral regurgitation (any degree of severity) Exclusion Criteria:  -  Patients with unstable cardiovascular or pulmonary disease  -  Patients with mixed valvular heart disease, corresponding to more than one type of  valve pathology (i.e.: Aortic stenosis and Aortic Regurgitation), or more than 1 valve  involved (i.e.: aortic stenosis and mitral regurgitation)

The study is a community interventional study by using an integrated back pain module (IBPM).  The purpose of this study is to find out if the module training has any benefit on Low Back  pain among ambulance drivers. The effectiveness of the module is determined by baseline  quality of life results compared with after the intervention program completed. An integrated back pain module (IBPM) will be implemented for ambulance drivers (Respondent)  in peninsular Malaysia. Pre-intervention assessment and post-intervention assessment will be  conducted in 18 government hospitals involved. There is nine Hospital in Perak that has been  selected as an intervention group and nine Hospital in Kelantan will be the Control group.  Two different regions are selected; the North region will be the intervention group (Perak)  while East Coast will be the control group (Kelantan). The clinical benefits of the IBPM  module low back pain and quality of life will be reported at the beginning and the end of the  intervention and after a period of 6 months follow up.  The protocol for the intervention group (Perak) included five components of the education  module (IBPM) such as the structure and function of the spine, causes of LBP, how to avoid  low back pain at the workplace, Exercise methods, and psychology management. The overall  objectives are to help ambulance driver manage their LBP and prevent future LBP recurrences.  The first step of the protocol is subjects are required to attend an introductory course for  one day and then the intervention will last for 6 months. Research staff will explain how to  operate and use the module. Subjects must comply with all the care and prevention guidelines  of the research module so that it achieves the expected results. They also need to complete  the checklist provided in the Edmodo software via their respective smartphones. Tokens in the  form of top-ups will be entered automatically after the checklist is received by researchers.  The exercise will be performed by participants 5 times per week for a total of 24 weeks. Each  individual session will take around 5 minutes to perform exercises independently and sending  their report through Edmodo. Light soft tissue exercises techniques such as active muscle  stretching, and strengthening exercises will be used as needed to facilitate the educational  module therapy. Inclusion Criteria:  -  Adult ≥ 18 years old.  -  Working experience ≥ 1 year Exclusion Criteria:  -  Patients with Uncontrolled Chronic Illness such as Hypertension, Diabetes Mellitus,  Osteoarthritis and Gout.  -  Injury or surgery of the spine

Endoscopic mucosal resection (EMR) is an effective and has been widely used technique for the  treatment of superficial colorectal neoplasms. Although, conventional EMR (CEMR) showed high  efficacy for the management of colorectal superficial neoplasms, there is problematic  limitation in this technique - incomplete resection. In literature, the anchoring-tip EMR  (AEMR), named as "Tip-in EMR" was first introduced in 2016 from Japan. Recently, several  retrospective studies have been suggested about the effectiveness of AEMR. However, there has  been no prospective randomized controlled study to identify its advantage over CEMR.  Therefore, the investigators performed a multicenter randomized controlled trial to estimate  the effectiveness of AEMR compared with CEMR for the endoscopic treatment of  intermediate-size (10 to 20 mm) colorectal polyps. After injection of normal saline solution mix, snaring was tried for CEMR. In AEMR, the snare  tip was projected from the sheath by 1-2 mm length. Consequently, a small mucosal incision  was made at proximal side of lesion. Then the snare was deployed progressively and adjusted  around the lesion trying to obtain free margins. At the final step of both conventional and  Tip-in EMR, the lesion was resected. Inclusion Criteria:  -  Intermediate-size (10 to 20 mm) colorectal polyps  -  Morphologically sessile (Is), slightly elevated (IIa), flat (IIb), and slightly  depressed (IIc) as Paris classification of superficial neoplastic lesions  -  Laterally spreading tumor (granular and nongranular type) as Kudo classification. Exclusion Criteria:  -  Pedunculated or excavated/ulcerated polyps  -  Polyps with features strongly suggestive of submucosal invasive carcinoma  -  Polyps in patients with inflammatory bowel disease, familial polyposis, electrolyte  abnormality, and coagulopathy  -  Residual lesions after endoscopic resection or presence of severe submucosal fibrosis.

This study is a single arm phase II trial including 53 patients with  T2N2-3M0、T3-4N0-3M0（III-IV） head and neck squamous cell carcinoma (HNSCC) eligible for  resection, who receive neo-adjvuant Camrelizumab combined with cisplatin and Nab-paclitaxel.  This proposed study will evaluate the efficacy and safety of preoperative administration of  Camrelizumab combined with chemotherapy in Head and Neck Squamous Cell Carcinoma (HNSCC) who  are about to undergo surgery. In this study, eligible subject will be enrolled into study arm to accept study treatment.  Objective response rate will be the primary outcome measures. Inclusion Criteria:  1. Confirmed pathologic and/or cytologic diagnosis of squamous cell carcinoma of head and  neck，T2N2-3M0、T3-4N0-3M0（III-IV）（AJCC 8.0）  2. Greater than or equal to 18 and less than 65 years of age at time of study entry.  3. ECOG performance status of 0 or 1.  4. Resectable or potentially resectable lesion, without distance metastasis;  5. Measurable disease as per RECIST 1.1.  6. Screening labs must meet the following criteria and must be obtained within 14 days  prior to registration:  7. Adequate hepatic、cardiac、brain and renal function as demonstrated by 1) Hematology:  WBC≥4000/μL、NE≥2.000/μL、HGB≥9 g/dL、PLT≥100000/μL； 2) Renal: Serum creatinine < 1.5x  ULN or CrCl > 60mL/min (if using the Cockcroft-Gault formula below): 3) Hepatic: Total  Bilirubin ≤ 1.5 x ULN (except subjects with Gilbert Syndrome, who can have total  bilirubin < 3 x ULN)；AST/ALT ≤ 3 x ULN and ALP≤3 x ULN；ALB≥3g / dL；  8. Ability to understand and willingness to sign an IRB approved written informed consent  document. Subject is willing and able to comply with the protocol for the duration of  the study including undergoing treatment and scheduled visits and examinations  including follow up. Exclusion Criteria:  1. Severe allergic reaction to any component of PD-1 monoclonal antibodies or other  monoclonal antibodies.  2. Active, known or suspected autoimmune disease, including dementia and epilepsy.  3. Has had another known invasive malignancy or unresectable cancer.  4. Coagulation dysfunction: (PT > 16S, APTT > 53s, TT > 21s, FIB < 1.5g / L), bleeding  tendency or thrombolysis, anticoagulation treatment.  5. Severe cardiac disease, lung dysfunction, heart function and lung function lower than  grade 3 (≤3).  6. Laboratory abnormality within 7 days before enrollment.  7. Has received prior therapy with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CTLA-4  antibody, or any other antibody or drug specifically targeting T-cell co-stimulation  or immune checkpoint pathways.  8. Subjects with a condition requiring systemic treatment with either corticosteroids or  other immunosuppressive medications before enrollment.  9. Has a known history of Human Immunodeficiency Virus (HIV).  10. Has a known history of Hepatitis B (defined as HBV DNA ≥1000 cps/mL is detected) or  known active Hepatitis C virus (defined as: HCV antibody positive) infection.  11. have received anti-tumor herbs within 4 weeks before randomization.  12. Pregnant or nursing women.

Multicentre study; observational, longitudinal prospective, case-control This is a new protocol to evaluate the mode of birth in women with a low-lying placenta. In  particular, we intend to propose a vaginal birth in women having a low-lying placenta with a  distance between the inferior placental edge and the internal cervical os, called  internal-os-distance (IOD) of > 5 mm, as assessed in the late III trimester using  transvaginal sonography.  Duration of the study:  -  Duration of the study: 54 months  -  Duration of enrollment: 42 months  -  Duration of follow-up completion of enrolled cases: 6 months  -  Duration of data analysis: 6 months  Study Design:  During the II trimester scan, all women presenting a placenta located in the lower uterine  segment will undergo evaluation by Transvaginal Sonography (TVS).  If a placenta previa or a low-lying placenta will be confirmed, the woman will be recruited  and asked to participate in our study, by signing a written informed consent. In addition  women attending the Maternity Triage with vaginal bleeding at < 316/7 weeks of gestation,  with a diagnosis of placenta previa or low-lying placenta and not requiring an emergency  delivery will be asked to participate and will be recruited after signing the informed  consent.  An expert Obstetrician will perform the TVS as scheduled, after inviting the woman to void.  The assessment will include:  -  the measurement of the IOD (first caliper on the internal cervical os and second caliper  on the inferior placental edge). In case of a marginal sinus, the distance between the  internal cervical os and the marginal sinus will also be assessed;  -  the cervical length (defined as shortened if ≤25 mm);  -  the placental edge thickness, measured within 1 cm from the meeting point between the  basal and the chorionic plate. The placental edge will be considered "thick" if > 1cm or  if the angle is >45°.  All women with a resolution of a previa or low-lying placenta will be assessed in accordance  with the protocol of each participating Maternity Unit, including a scan assessment at 38-39  weeks of gestation or within 28 days from the due date.  Calculation of sample size / power:  Considering that the incidence of previa and low-lying placenta is approximately 2% at the II  trimester scan and 0.4% at birth, and assuming a C.I. of 19% in the probability of vaginal  birth in women with low-lying placenta/resolved low-lying (> 20 mm), 27 women will be needed  for each participating Maternity Unit at the late III trimester scan. Anticipating a 10% drop  out, 30 women will be needed to achieve a 95% statistical power to identify a clinically  relevant difference in the rate of vaginal birth. This leads to the need of recruiting 150  women at the II trimester scan.  CRF and data management:  All data will be recorded through CRF provided by the promoter center and the database will  be based on Microsoft Excel.  A sample of about 20-30 patients for each enrollment center is necessary to have a  statistical power of 95% in detecting a clinically relevant difference in outcomes in the  various study groups.  Analysis plan:  Descriptive statistics will be performed for all variables evaluated in the study population.  Variables will be described by mean and standard deviation if normally distributed, otherwise  by median and interquantile range; proportions will be used for categorical variables. The  quantitative variables, among the study groups defined by the IOD at the last TVS, will be  compared by parametric and non-parametric tests, whereas the categorical variables will be  compared using Pearson's chi2 test (Fisher exact test where appropriate). The analyses for  the primary outcome measure will be performed among women admitted to labor. A multivariate  analysis will be conducted to assess the association between obstetric variables and vaginal  birth.  A p-value<0.05 will be considered significant. Inclusion Criteria:  -  Minimum age of 18  -  Women with placenta previa or low-lying placenta confirmed by TVS at 19-23 6/7 weeks  of gestation.  Women attending Maternity Triage with vaginal bleeding at < 32 weeks of gestation, with a  diagnosis of placenta previa or low-lying placenta and not requiring an emergency delivery.  -  Women with a normally located placenta at the II trimester ultrasound scan, at 19-23  6/7 week of gestation (control group)  -  Single pregnancy  -  Signature of the informed consent to participate in the study  Note: Women of the "control group" will be recruited in a 1:3 ratio. After the inclusion of  1 case, 3 women with a normally located placenta will be recruited, according to the parity  of the woman representing the case (e.g.: 1 CASE= nulliparous woman, 3 CONTROLS= 3  nulliparous women). Exclusion Criteria:  -  Suspected or confirmed invasive placentation (i.e., placenta accreta)  -  Vaginal bleeding requiring emergency delivery  -  Inability to meet the conditions set out in the study protocol

This phase I/II trial is studying the side effects and best dose of sorafenib, gemcitabine,  and capecitabine and to see how well they work in treating patients with unresectable and/or  metastatic kidney cancer. Sorafenib may stop the growth of tumor cells by blocking some of  the enzymes needed for cell growth and by blocking blood flow to the tumor. Drugs used in  chemotherapy, such as gemcitabine and capecitabine, work in different ways to stop the growth  of tumor cells, either by killing the cells or by stopping them from dividing. Giving  sorafenib together with gemcitabine and capecitabine may kill more tumor cells. OBJECTIVES:  I. Determine the maximum tolerated dose (MTD) and dose-limiting toxicity (DLT) of sorafenib  administered in combination with gemictabine and capecitabine in patients with advanced renal  cell carcinoma.  II. Determine the objective response rate for sorafenib in combination with gemictabine and  capecitabine in patients with advanced renal cell carcinoma.  III. Determine the duration of overall survival and progression free survival in these  patients.  OUTLINE: This is a multicenter, non-randomized, phase I dose-escalation study followed by a  phase II study.  PHASE I: Patients receive sorafenib* orally (PO) twice daily (BID) on days 1-21, gemcitabine  intravenously (IV) over 30 minutes on days 1 and 8, and capecitabine PO BID on days 1-14.  Treatment repeats every 21 days for at least 3 courses in the absence of unacceptable  toxicity or disease progression.  Cohorts of 3-6 patients receive escalating doses of sorafenib, gemcitabine, and capecitabine  until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose  preceding that at which 2 of 6 patients experience dose-limiting toxicity. An additional 6  patients are treated at the MTD.  Note: *Patients who complete at least 3 courses of treatment with objective response or  stable disease but are deemed poor candidates for continued chemotherapy may continue  treatment with sorafenib  PHASE II: Patients receive sorafenib 200mg orally twice a day on days 1-21, gemcitabine 750  mg/m2 intravenously on days 1 & 8, and capecitabine 415 mg/m2 orally twice a day on days 1-14  of each 21 day cycle, as in phase I at the MTD determined in phase I.  After completion of study treatment patients are followed periodically. Inclusion Criteria:  -  Patients must have histologically or cytologically confirmed renal cell carcinoma that  is unresectable and/or metastatic; patients with collecting duct carcinoma,  oncocytomas, or transitional cell carcinoma are not eligible; patients with  sarcomatoid renal cell carcinoma are eligible, but those with pure sarcomas are not;  histologic documentation of metastatic disease is not required; clinical confirmation,  but not pathologic staging, of metastatic disease is required  -  Patients must have measurable disease, defined as at least one lesion that can be  accurately measured in at least one dimension (longest diameter to be recorded) as >=  20 mm with conventional techniques or as >= 10 mm with spiral computed tomography (CT)  scan  -  Patients may have received one prior immunotherapy based regimen (i.e. interleukin-2  or interferon alpha) ending >= 4 weeks prior to enrollment  -  Patients may have received up to 2 prior regimens containing mitogen-activated protein  kinases (MAPK), vascular endothelial growth factor (VEGF) pathway inhibitors (e.g.  sunitinib or bevacizumab) and/or mammalian target of rapamycin (mTOR) inhibitor (e.g.  temsirolimus) ending >= 4 weeks prior to enrollment  -  Life expectancy of more than 3 months  -  Eastern Cooperative Oncology Group (ECOG) =< 2 OR Karnofsky >= 60%  -  Leukocytes >= 3000/uL  -  Absolute neutrophil count >= 1,500/uL  -  Platelet count >= 100,000/uL  -  Total bilirubin =< 1.5 x institutional upper limit of normal (IULN)  -  Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase  [SGOT])/alanine aminotransferase (ALT) (serum glutamic pyruvate transaminase [SGPT])  =< 2.5 x IULN  -  Creatinine =< 1.5 x IULN OR creatinine clearance >= 60 mL/min/1.73m^2 for patients  with creatinine levels above institutional normal  -  The effects of sorafenib on the developing human fetus at the recommended therapeutic  dose are unknown; for this reason and because raf kinase inhibitor agents as well as  other therapeutic agents used in this trial are known to be teratogenic, 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; should a woman become pregnant or suspect she is pregnant  while participating in this study, she should inform her treating physician  immediately  -  Ability to understand and the willingness to sign a written informed consent document Exclusion Criteria:  -  Patients may not have received prior chemotherapy; if patients have had prior  definitive or other surgery, prior radiation therapy, they must have fully recovered  from the effects of therapy with at least 4 weeks recovery time; for patients who have  had a surgical biopsy only, they must have simply recovered  -  Patients may not be receiving any other investigational agents  -  Patients with known active brain metastases should be excluded from this clinical  trial because of their poor prognosis and because they often develop progressive  neurologic dysfunction that would confound the evaluation of neurologic and other  adverse events; previously treated brain metastases are allowed if they show no  evidence of progression on CT or magnetic resonance imaging (MRI) at least 8 weeks  after completion of surgery and/or radiotherapy  -  History of allergic reactions attributed to compounds of similar chemical or biologic  composition to sorafenib, gemcitabine and capecitabine  -  No concurrent megestrol is permitted; no megestrol therapy within 4 weeks prior to  protocol treatment is allowed; no concurrent cytochrome P450 enzyme-inducing  antiepileptic drugs (phenytoin, phenobarbitol or carbamazepine), rifampin, or St.  John's wort  -  Uncontrolled intercurrent illness including, but not limited to, uncontrolled  hypertension, ongoing or active infection, symptomatic congestive heart failure,  unstable angina pectoris, cardiac arrhythmia, pulmonary disease including asthma,  chronic bronchitis, emphysema with requirements for chronic oxygen use or psychiatric  illness/social situations that would limit compliance with study requirements  -  Pregnant women are excluded from this study because sorafenib is a kinase inhibitor  agent with the potential for teratogenic or abortifacient effects; because there is an  unknown but potential risk for adverse events in nursing infants secondary to  treatment of the mother with sorafenib, breastfeeding should be discontinued if the  mother is treated with sorafenib; the potential risks may apply to other agents used  in this study  -  Because patients with immune deficiency are at increased risk of lethal infections  when treated with marrow-suppressive therapy, human immunodeficiency virus  (HIV)-positive patients receiving combination anti-retroviral therapy are excluded  from the study because of possible pharmacokinetic interactions with sorafenib,  gemcitabine, or capecitabine administered during the study; appropriate studies will  be undertaken in patients receiving combination ant-retroviral therapy when indicated  -  Any swallowing dysfunction leading to difficulty taking the investigational therapy or  capecitabine  -  Prior treatment with sorafenib  -  Patients with any history or evidence of a bleeding diathesis  -  Patients on therapeutic anticoagulation with coumarins (e.g. warfarin); prophylactic  coumarin-based anticoagulation (i.e. low dose warfarin) for venous or arterial access  devices is allowed provided that the requirements for prothrombin time (PT),  international normalization ratio (INR) and/or partial thromboplastin time (PTT) are  met; prophylactic or therapeutic low molecular weight heparin is allowed; patients  with known brain metastases are excluded (even if treated and stable) if they are also  on therapeutic doses of anticoagulation  -  Patients with known dihydropyrimidine dehydrogenase deficiency

To evaluate the use of an occlusion balloon (Bridge™ Occlusion Balloon, Spectranetics) within  the Superior Vena Cava in lead extraction patients. This study will evaluate the use of an occlusion balloon (Bridge™ Occlusion Balloon,  Spectranetics) within the Superior Vena Cava in lead extraction patients. This will be  performed in a non-emergent setting to allow for evaluation of how best to integrate this new  technology into the investigators clinical practice. The study will focus on the effect of  the Bridge balloon on the patient preparation clinical workflow, ease of  insertion/positioning/deployment, and the ability to recognize proper inflation and vein  sealing under fluoroscopy. Understanding these factors will help build a more robust clinical  workflow with the goal of better patient outcomes in the case of an Superior Vena Cava  injury. The images and data generated during this study can help in dissemination of the  practical use knowledge to fellow lead extractors.  At the time of the protocol registration, the timeframe 12 months was entered, this was  actually the anticipated length of the study at registration. The timeframe was corrected to  33 minutes (average time) at the time of results entry. Inclusion Criteria:  -  Subject age more than 18 years  -  Lead extraction patients Exclusion Criteria:  Lead extraction patients with:  -  Superior Vena Cava occlusion or stenosis.  -  Significant vegetation.  -  Hemodynamic instability.  -  Class IV heart failure  -  Creatinine > 2.0mg/dL  -  Patients > 85 years old

An outpatient rehabilitation program for children (6 months to 3 years old) with Spinal  Muscular Atrophy (SMA) treated with genetic based therapies is being studied. Participants  will participate in a 12-week therapy program where they receive 45 minutes each of  occupational therapy and physical therapy each week. Home exercises will also be prescribed  to be completed 5 days per week. At the end of the therapy program, there will be a 12-week  period of no therapy where only home exercises will be completed. Assessments and program  evaluation will occur at the beginning (Week 0) and end of the rehabilitation program (Week  24), then at the end of the no therapy block (week 24). The standard of care for SMA has historically been physical therapy (PT) and occupational  therapy (OT) often focused on strategies that reduce the risk of secondary side effects such  as joint tightness. Recently, three genetic based therapies: nusinersen, onasemnogene  abeparvovec and risdiplam, have been approved as treatment by Health Canada. Genetic based  therapies have provided improvements in physical function for children with SMA. Currently,  there is no evidence-based guidance regarding rehabilitation to increase function for  children with SMA that have received genetic based therapies. Additionally, there is a lack  of published evidence regarding the type of rehabilitation programs and the impact that  rehabilitation has on physical function.  An outpatient rehabilitation program for children (6 months to 3 years old) with Spinal  Muscular Atrophy (SMA) treated with genetic based therapies is being proposed and its  feasibility being evaluated. Participants will participate in a 12-week therapy program where  they receive 45 minutes each of occupational therapy and physical therapy each week. Home  exercises will also be prescribed to be completed 5 days per week. At the end of the therapy  program, there will be a 12-week period of no therapy where only home exercises will be  completed. Assessments and program evaluation will occur at the beginning (Week 0) and end of  the rehabilitation program (Week 24), then at the end of the no therapy block (week 24). Inclusion Criteria:  -  SMA (Type I, II or III) diagnosis;  -  Receives genetic based therapy;  -  Aged 6 months to 3 years old;  -  Able to participate in weekly therapy at Holland Bloorview (i.e., can attend in-person  sessions);  -  Able to bring appropriate respiratory equipment to weekly therapy sessions, if  required;  -  Substitute decision makers (SDMs) must be able to speak and read English;  -  Child participant must be able to understand/follow directions in English, as age  appropriate;  -  SDMs must consent to participate on behalf of their child. Exclusion Criteria:  -  Live outside of Ontario;  -  Tracheostomy or use of daytime ventilation (excluding ventilation used during naps).

The aim of this study is to evaluate the prokinetic effect of metoclopramide on gastric  emptying in critically ill mechanically ventilated patients . More than 50% of patients in ICU have gastric dysmotility, which leads to slow gastric  emptying(GE) and high gastric residual volume (GRV) and is associated with increased  mortality in these patients Inclusion Criteria:  1. Patients' age 20 - 60 years.  2. Either gender.  3. Mechanically ventilated head trauma patients.  4. Patients receiving enteral feeding via nasogastric tube. Exclusion Criteria:  1. Patients with contraindications to enteral feeding.  2. Patients with extrapyramidal manifestations.  3. Patients with known allergy to metoclopramide.  4. Patients with seizures.  5. Patients with renal or hepatic diseases.

The purpose of this study is to assess the efficacy, safety, and pharmacokinetics of  niraparib in men with metastatic castration-resistant prostate cancer (mCRPC) and  deoxyribonucleic acid (DNA) repair anomalies. This is a multicenter and open-label (participants and researchers are aware of the treatment  that participants are receiving) study that consists of 4 phases: a Prescreening Phase for  biomarker evaluation only, a Screening Phase, a Treatment Phase (Cycle 1 Day 1 and will  continue until the study drug is discontinued), a Follow-up Phase (every 3 months after end  of treatment visit), and a Long-term Extension Phase (until participants no longer derive  benefit from treatment or until further notification on different means of study treatment).  Participants will be monitored for safety during the study period, and up to 30 days after  the last dose of study drug. Inclusion Criteria:  -  Histologically confirmed prostate cancer (mixed histology is acceptable, with the  exception of the small cell pure phenotype, which is excluded)  -  Received a taxane-based chemotherapy for the treatment of metastatic prostate cancer  with evidence of disease progression on or after treatment, or discontinued from a  taxane-based chemotherapy due to an adverse event  -  Received a second-generation or later androgen receptor (AR)-targeted therapy (for  example, abiraterone acetate plus prednisone, enzalutamide, apalutamide) for the  treatment of metastatic prostate cancer with evidence of disease progression or  non-metastatic castration-resistant prostate cancer with evidence of subsequent  metastasis  -  Biomarker-positive by at least one of the following criteria: (a) Biallelic  deoxyribonucleic acid (DNA)-repair anomaly based on a sponsor validated blood or  tissue assay; (b) Germline pathogenic Breast Cancer gene (BRCA) 1 or BRCA2 by any test  (somatic local results must be confirmed as positive by the sponsor-validated assay  before dosing)  -  Progression of metastatic prostate cancer in the setting of castrate levels of  testosterone or history of bilateral orchiectomy at study entry Exclusion Criteria:  -  Prior treatment with a poly (adenosine diphosphate [ADP] ribose) polymerase (PARP)  inhibitor  -  Prior platinum-based chemotherapy for the treatment of prostate cancer  -  Known history or current diagnosis of myelodysplastic syndrome (MDS)/acute myeloid  leukemia (AML)  -  Symptomatic or impending cord compression  -  Symptomatic brain metastases

MyRisk: Efficacy and safety evaluation of oral Akynzeo® in patients receiving MEC at high  risk of developing CINV based on a prediction tool. A multinational and multicenter study.  Antiemetic guidelines recommendations are based on the emetogenic potential of the  chemotherapy. Chemotherapy (CT) agents are divided in Highly, Moderately, Low and Minimally  Emetogenic potential.  In addition to type of chemotherapy, several patient-related risk factors can increase the  risk of CINV (chemotherapy-induced nausea and vomiting). Currently, there is limited  consensus surrounding the most relevant patient risk factors that may predict the risk of  CINV. Based on a recent study by Dranitsaris et al. (Dranitsaris et al. Ann Oncol. 2017 Jun  1; 28(6):1260-1267.), eight (8) predictive factors have been identified and an algorithm has  been developed to incorporate these factors into the optimal selection of prophylactic  antiemetics:  1. nausea and/or vomiting in the prior cycle of chemotherapy  2. use of non-prescribed antiemetics at home in the prior cycle of chemotherapy  3. platinum or anthracycline-based chemotherapy  4. age < 60 years  5. expectations for (anticipating) nausea and/or vomiting  6. <7 h of sleep the night before chemotherapy  7. history of morning sickness during previous pregnancy  8. cycle of chemotherapy (A negative association between risk and number of cycles was  identified where the hazard for CINV was highest in cycles 1 and 2, with a gradual  decline and plateau from cycle 3 onward).  The clinical application of this prediction tool has the potential to be an important  resource for clinicians and may help to enhance patient care by optimizing the use of the  antiemetics in a proactive manner. Antiemetic guideline recommendations are based on the emetogenic potential of chemotherapy  and involve 4 levels of classification of intravenous chemotherapy agents, i.e., high,  moderate, low and minimal; these have been accepted by major organisations. Moderate  emetogenic chemotherapy (MEC) results in acute vomiting in 30% to 90% of cancer patients in  the absence of antiemetic therapy. In addition to the chemotherapy type, several  patient-related risk factors and clinical characteristics can increase CINV risk. These can  include use of antiemetics inconsistent with international guidelines, younger age,  prechemotherapy nausea, no complete CINV response in an earlier cycle, history of  nausea/vomiting, (trait) anxiety, fatigue experience, and expectations of nausea/vomiting.  Other studies have largely confirmed some of the key risk factors for CINV (history of  vomiting during pregnancy, history of motion sickness, age, gender) and added other factors  such as (chronic) alcohol consumption, body surface area, fewer hours slept the night prior  to infusion, or advanced stage cancer. Currently, there is a limited consensus surrounding  the most relevant patient risk factors that may predict CINV risk. Based on a recent study by  Dranitsaris et al. eight predictive factors have been identified, and an algorithm has been  developed to combine these patient-related risk factors into the optimal treatment of  prophylactic antiemetics. These include:  1. nausea and/or vomiting in the prior cycle of chemotherapy  2. use of non-prescribed antiemetics at home in the prior cycle of chemotherapy  3. platinum or anthracycline-based chemotherapy  4. age < 60 years  5. expectations for (anticipating) nausea and/or vomiting  6. <7 h of sleep the night before chemotherapy  7. history of morning sickness during previous pregnancy  8. cycle of chemotherapy (A negative association between risk and number of cycles was  identified where the hazard for CINV was highest in cycles 1 and 2, with a gradual  decline and plateau from cycle 3 onward).  Akynzeo®, an oral combination of the neurokinin 1 receptor antagonists (NK1 RA), netupitant  and the 5-hydroxytryptamine (HT3) receptor antagonists (5-HT3 RA), palonosetron, is  recommended by guidelines for the prevention of CINV. Akynzeo® has been evaluated in a  multicentre, randomised, double-blind, double-dummy phase II clinical trial at various dose  ranges among 694 cisplatin-treated cancer patients from 44 sites (two countries); each NEPA  (netupitant-palonosetron) dose significantly improves CINV prevention in cancer patients.  Similar results were obtained in another international, randomised, double-blind and parallel  group phase III clinical trial; NEPA prevented CINV in patients receiving MEC.  The current study primarily aimed to evaluate whether Akynzeo® leads to a higher response  rate compared with standard care in MEC regimen-treated patients who are identified to be at  high risk based on the algorithm. Inclusion Criteria:  -  Adult patients aged ≥18 years  -  Patients with a risk score of ≥ 13 as calculated by the algorithm - see 3.6.3.1.  Baseline/screening: VISIT 0  -  Signed Informed consent  -  Both sexes  -  Patients with diagnosis of any cancer scheduled and intended to be treated for three  consecutive cycles with a single dose of any IV MEC regimen, per cycle, including  adjuvant or neo-adjuvant chemotherapy  -  Patients with Eastern Cooperative Oncology Group (ECOG) performance status 0, 1 or 2  -  Use of Standard of Care defined as a 5-HT3 RA + Dexamethasone (or equivalent  corticosteroid) based-regimen on day 1 of chemotherapy for CINV prevention  -  Naïve and non- naïve to chemotherapy  -  The enrolled women should be a) of non-childbearing potential or b) of childbearing  potential using reliable contraceptive measures and having a negative urine pregnancy  test done by health care team within 1-24 hours before dosing the antiemetic treatment  in both arms and outcome recorded in the medical records  -  Able to comply with study requirements Exclusion Criteria:  -  Patients receiving highly emetogenic chemotherapy (including  anthracycline+cyclophosphamide-based chemotherapy)  -  Patients receiving oral moderately emetogenic chemotherapy drugs  -  Patients receiving opioids within 2 weeks prior to trial enrollment (longer use  allowed)  -  Use of olanzapine as prophylaxis of CINV  -  Patients scheduled to receive radiotherapy concurrently with chemotherapy  -  Any illness or condition that, in the opinion of the physician, may confound the  results of the study or pose unwarranted risks in administering the investigational  product to the patient.  -  Patients with mechanical risk factors for nausea (i.e. intestinal obstruction)  -  Patients with liver disease (as nausea is a common presenting symptom)  -  Patients with metabolic risk factors for nausea (i.e. electrolyte imbalances causing  nausea/vomiting)  -  Chronic treatment with steroids (with the exception of inhaled or topical steroids)  -  Pregnancy and/or breast-feeding women  -  Women of childbearing potential refusing to use effective contraception during the  whole study treatment and up to one month after study treatment with Akynzeo®  -  Use of Standard of Care including an NK-1 RA-based regimen to prevent CINV

Children with Down syndrome often present with problems of posture & balance and mobility.  Balance training is an important component of physical activity interventions, with growing  evidence that it can be beneficial for children with DS.  Objective: To determine the effect core stability exercises and balance training in postural  control among Down syndrome. This study was a randomized clinical trail. Children with Down Syndrome were determined on  inclusion & exclusion criteria. Children with Down syndrome were arbitrarily allocated into  two groups with ages ranged from 5 to 17 years. The sample size was 20 patients. They were  assigned randomly into two groups. Group 1 received balance training and Group 2 received  core stability exercises. The duration of treatment was 6 weeks. Data is collected from  Comprehensive Rehabilitation center Chakwal Postural stability was evaluated pre and post  treatment by pediatric berg balance scale. Values which were obtained after this intervention  were analyzed for any change using SPSS Inclusion Criteria:  -  Trisomy 21 by genetic karyotype  -  A confirmed diagnosis of Down syndrome by a paediatric neurologist, having no  neurological or mobility disorders,  -  independent standing and walking abilities,  -  Joint Laxity , low muscle tone and psychomotor development deficits  -  Normal vision and hearing Exclusion Criteria:  -  A history of congenital heart defects and orthopedic  -  surgery in the past year and severe mental retardation.  -  Seizure  -  Severe visual or auditory disturbances,  -  Weight less than the 3rd percentile of Down syndrome  -  Multiple sclerosis or epilepsy

This is a pragmatic trial of SHARING Choices. Components of SHARING Choices include:  1. A letter from the clinic introducing an initiative to prepare persons and families for  Advance Care Planning (ACP);  2. Access to a facilitator trained to lead ACP discussions;  3. Patient-family agenda-setting to align perspectives about the role of family and  stimulate discussion about ACP;  4. Facilitated registration to the patient portal (for patient and family) as desired;  5. Education & resources about Alzheimer's Disease and Related Dementias (ADRD) for clinic  staff. Engaging family in primary care is particularly important in Alzheimer's Disease and Related  Dementias (ADRD) because of the important role assumed in medical decision-making, especially  at the end of life. The investigators, study seeks to improve communication in primary care  through methods to proactively engage family in ongoing interactions with primary care and  stimulate and support Advance Care Planning (ACP) for all older adults and attention to ADRD  in primary care throughout the ADRD disease trajectory. The investigators' premise is that  individuals and families appreciate primary care involvement in ACP and information and  referrals for ADRD needs, but that individual, family, and system factors including time,  knowledge, and resources often inhibit these conversations from occurring.  SHARING Choices integrates communication strategies that have been individually found to be  effective but have thus far been deployed in isolation of one another. The investigators  focus on all older primary care patients because of the importance of addressing ACP early,  the under-diagnosis of ADRD and the greater implementation potential of a protocol with broad  applicability.  Components of SHARING Choices include:  1. A letter from the clinic introducing an initiative to prepare persons and families for  Advance Care Planning (ACP);  2. Access to a facilitator trained to lead ACP discussions;  3. Patient-family agenda-setting to align perspectives about the role of family and  stimulate discussion about ACP;  4. Facilitated registration to the patient portal (for patient and family) as desired;  5. Education & resources about ADRD for clinic staff. Inclusion Criteria:  Practices included in this trial are:  -  Affiliated with Johns Hopkins Community Physicians (JHCP) or MedStar Health;  -  A primary care practice, defined as adult internal medicine, family medicine, or  geriatric medicine;  -  Have 2 or more practicing clinicians; and  -  Have more than 500 patients aged 65 and over currently receiving care.  Patients included in this trial are:  -  Age 65 and older, and  -  Established patient of primary care clinician at participating practice (>1 prior  visit at the clinic). There will be no formal enrollment of participants into this  pragmatic trial as this is a clinic-level initiative that will be available and  offered to all eligible patients at clinics randomized to the intervention. Exclusion Criteria:  Primary care practices affiliated with Johns Hopkins Community Physicians (JHCP) or MedStar  Health that are:  -  Not a primary care practice, defined as adult internal medicine, family medicine, or  geriatric medicine;  -  Have fewer than 2 practicing clinicians; and  -  Have fewer than 500 patients aged 65 and over currently receiving care.  Patients under the care of primary care practices affiliated with Johns Hopkins Community  Physicians (JHCP) or MedStar Health that are:  -  Less than 65 years of age, or  -  Not established patients.

There is a debate in the literature about the effect of NSLBP on pelvic tilt and its effect  on balance, sensory integration and functional disability so we need this study to fill the  aforementioned gap in literature in this field. So the purpose of the study is to evaluate  posterior pelvic tilt effect on overall dynamic balance, sensory integration and functional  disability in patients with non-specific low back pain. The LBP became one of the biggest problems for public health systems in the world during the  second half of the 20th century. The lifetime prevalence of LBP is reported to be as high as  84%, and the prevalence of chronic LBP is about 23%, with 11-12% of the population being  disabled by LBP. Prevalence of LBP was 53.2%. It was more among female patients (62.8%) than  among male patients (38.3%) among attendants to a Family Health Center in Egypt.  Additionally, studies have observed relationships between chronic non-specific LBP and a  posteriorly shifted center of gravity, impaired proprioception, and decreased muscular  strength, activation and endurance of the trunk and hips. Balance is impaired in individuals  with chronic low back pain when compared to healthy individuals.  Most of these studies supposed that postural mal-alignment involves deviations in only one  direction which is toward lordosis and anterior pelvic tilt. However, clinical experience  suggests that some patients with back pain have the opposite problem which is a much reduced  lordotic curve and a posterior pelvic tilt. If the true relationship between posture and low  back pain disability is curvilinear instead, this could explain why the studies so far have  shown weak or no relationships. Inclusion Criteria:  1. Fifty patients with chronic low back pain or repeated non-specific back pain for more  than three months.  2. Both sex with posterior pelvic tilt (-0.7 ± 6.5°)and decreased lumbar lordosis, for  (Group A) and normal anterior pelvic tilt angle between 5° and 13° for (Group B)  3. Their ages were ranged from 20-35 years.  4. Body Mass Index from 18-25 Kg/m² . Exclusion Criteria:  1. Previous back surgery.  2. Signs and symptoms of gross spinal instability.  3. Radiological diagnosis of spondylolysis or spondylolisthesis.  4. Acute low back pain.  5. Disc prolapse or herniation.  6. Any neurological, orthopedic, and vestibular disorders affecting the balance system.  7. Flexion and extension restriction of the lumbar region.  8. Other conditions that affected the normal functioning of the central and peripheral  nervous system such as alcohol abuse, addiction, dementia, and cognitive disorders.

This study will establish a comprehensive exon database of ALS patients, lay the foundation  for screening the genes related to the occurrence and development of the disease, support the  theory of ALS disease progression from peripheral to central, and reveal the correlation  between the functional level of peripheral nerve and the prognosis of the disease at the gene  level for the first time, and provide the basis for the mechanism research at the molecular  level. Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease that selectively  invades superior and inferior motor neurons. Because there is no effective treatment, it is  urgent to find the risk factors of ALS to guide the prevention and slow down the disease  progression. In the early stage of the disease, the peripheral motor injury is more rapid and  sensitive than the central response, which is an ideal window to observe the state of the  disease. Protecting peripheral nerve integrity and maintaining its function can slow down the  death of superior neurons, effectively relieve symptoms and prolong survival time, which has  also been confirmed in patients with multiple stem cell-derived motor neurons and SOD1 G93A  disease model mice. Reexamination of the role of peripheral motor nerve related factors in  the development of ALS is of great significance for the study of disease mechanism, clinical  classification, prognosis, evaluation of drug trial efficacy and individualized treatment  plan. Previous studies have shown that NEFL gene, as the coding gene of light chain of neuron  cytoskeleton, is closely related to axonal function, and its polymorphism is related to the  occurrence and severity of axonal Charcot Marie Tooth disease. Exploring the role of similar  peripheral nerve related genes in the progression of ALS will help us better understand the  disease from the genetic level, establish an accurate and stable prognosis prediction model,  and guide early treatment. This study will establish a comprehensive exon database of ALS  patients, lay the foundation for screening the genes related to the occurrence and  development of the disease, support the theory of ALS disease progression from peripheral to  central, and reveal the correlation between the functional level of peripheral nerve and the  prognosis of the disease at the gene level for the first time, and provide the basis for the  mechanism research at the molecular level. Inclusion Criteria:  1. Since February 2021, he has been in the Department of Neurology, the Third Hospital of  Beijing Medical University. He was diagnosed amyotrophic lateral sclerosis according  to the revised EI Escorial diagnostic criteria of 2004 edition, and the patients  within one year of onset.  2. Informed consent has been signed. Exclusion Criteria:  1. Patients with ALS like syndrome caused by autoimmune diseases, paraneoplastic syndrome  and simple demyelinating lesions were excluded.

The QL 2 block is a novel fascial plane block recently described by Blanco and colleagues in  which local anesthetic is deposited adjacent to the antero-lateral aspect of the quadratus  lumborum muscle. This results in posterior spread of local anesthetic through the middle  layer of the thoraco-lumbar fascia, which theoretically communicates with the paravertebral  space resulting in potentially longer-lasting and denser analgesia than wound infiltration.  The QL 2 block derives from the TAP block, which is also a fascial plane block that is  commonly used to treat pain following surgery involving the anterior abdominal wall. However,  the QL block's more posterior location has recently been shown to provide a longer lasting  and more profound analgesic effect than the TAP block, possibly by communicating with the  paravertebral space. Although the TAP has been shown to be effective in a variety of surgical  procedures involving an anterior abdominal wall incision including laparoscopic bariatric  surgery the QL 2 block has until now, not been studied in the context of bariatric surgery. The QL 2 block is a novel fascial plane block recently described by Blanco and colleagues in  which local anesthetic is deposited adjacent to the antero-lateral aspect of the quadratus  lumborum muscle. This results in posterior spread of local anesthetic through the middle  layer of the thoraco-lumbar fascia, which theoretically communicates with the paravertebral  space resulting in potentially longer-lasting and denser analgesia than wound infiltration.  Like the more commonly used transversus abdominis plane (TAP) block, the QL 2 block targets  the anterior rami of T7-T12, ilioinguinal, iliohypogastric, and the lateral cutaneous  branches of L1-L3. The QL 2 block derives from the TAP block, which is also a fascial plane  block that is commonly used to treat pain following surgery involving the anterior abdominal  wall. However, the QL block's more posterior location has recently been shown to provide a  longer lasting and more profound analgesic effect than the TAP block, possibly by  communicating with the paravertebral space. Although the TAP has been shown to be effective  in a variety of surgical procedures involving an anterior abdominal wall incision including  laparoscopic bariatric surgery the QL 2 block has until now, not been studied in the context  of bariatric surgery. Conventional therapy has consisted of surgical infiltration of the  incision ports with bupivacaine 0.25%. The study team proposes a study to compare the  analgesic effects of the QL 2 block with conventional therapy, consisting of surgical wound  infiltration, for postoperative analgesia following laparoscopic gastric sleeve gastrectomy. Inclusion Criteria:  -  Patients scheduled to undergo laparoscopic gastric sleeve gastrectomy  -  18-65 years of age  -  BMI> 35 kg/m2. Exclusion Criteria:  -  Contraindications to administration of local anesthesia (e.g. local anesthetic  allergy)  -  Contraindication/allergy to acetaminophen or ketorolac  -  History of substance abuse or chronic opioid use  -  Coagulopathy  -  Patients receiving systemic anticoagulation  -  Local infection  -  ASA 4

The aims of the study are to describe the injury patterns among recreational skiers and  snowboarders in China and to provide primary data to guide the reconstruction of regional  healthcare facilities to deal with the increasing number of participants in snow sports. A retrospective study was performed in Ski Resorts in Chongli, China. 5000-10000 injured  skiers and snowboarders will be recruited. Data of all injury patients in the resort clinic  will be collected. Patients' information, including sex, age, equipment, skill level and  injured body part, will be analysed. Inclusion Criteria:  -  Skiing and snowboarding injuries Exclusion Criteria:  -  Skiing and snowboarding visitors without injuries

In this comparative prospective study, we aim to compare the classic Macintosh laryngoscope  and the Mac Grath videolaryncoscope in ICU covid 19 patients recruiting intubation and  invasive mechanical ventilation.  patients meeting inclusion criteria were randomized in 2 groups: MacGrath and Macintosh.  we collected anthropometric and intubation data among all patients, and the 2 groups were  compared regarding the time for intubation, the need of alternative techniques to intubate  and the impact on the oxygenation by recording the lowest SPO2. In this comparative prospective study, we aim to compare the classic Macintosh laryngoscope  and the Mac Grath videolaryncoscope in ICU covid 19 patients recruiting intubation and  invasive mechanical ventilation.  All hypoxemic COVID19 patients requiring intubation were enrolled in this trial.  all patients had a preoxygenation with non invasive ventilation with 100% oxygen.  patients meeting inclusion criteria were randomized in 2 groups: MacGrath and Macintosh.  we collected anthropometric and intubation data among all patients, and the 2 groups were  compared regarding the time for intubation, the need of alternative techniques to intubate  and the impact on the oxygenation by recording the lowest SPO2. Inclusion Criteria:  -  All COVID 19 hypoxemic patients requiring tracheal intubation Exclusion Criteria:  -  hypoxemic cardiac arrest before intubation