The Contribution of L-Type Cav1.3 Channels to Retinal Light Responses.

Abstract: L-type voltage-gated calcium channels (LTCCs) regulate tonic neurotransmitter release from sensory neurons including retinal photoreceptors. There are three types of LTCCs (Cav1.2, Cav1.3, and Cav1.4) expressed in the retina. While Cav1.2 is expressed in all retinal cells including the Müller glia and neurons, Cav1.3 and Cav1.4 are expressed in the retinal neurons with Cav1.4 exclusively expressed in the photoreceptor synaptic terminals. Mutations in the gene encoding Cav1.4 cause incomplete X-linked congenital stationary night blindness in humans. Even though Cav1.3 is present in the photoreceptor inner segments and the synaptic terminals in various vertebrate species, its role in vision is unclear, since genetic alterations in Cav1.3 are not associated with severe vision impairment in humans or in Cav1.3-null (Cav1.3-/-) mice. However, a failure to regulate Cav1.3 was found in a mouse model of Usher syndrome, the most common cause of combined deafness and blindness in humans, indicating that Cav1.3 may contribute to retinal function. In this report, we combined physiological and morphological data to demonstrate the role of Cav1.3 in retinal physiology and function that has been undervalued thus far. Through ex vivo and in vivo electroretinogram (ERG) recordings and immunohistochemical staining, we found that Cav1.3 plays a role in retinal light responses and synaptic plasticity. Pharmacological inhibition of Cav1.3 decreased ex vivo ERG a- and b-wave amplitudes. In Cav1.3-/- mice, their dark-adapted ERG a-, b-wave, and oscillatory potential amplitudes were significantly dampened, and implicit times were delayed compared to the wild type (WT). Furthermore, the density of ribbon synapses was reduced in the outer plexiform layer of Cav1.3-/- mice retinas. Hence, Cav1.3 plays a more prominent role in retinal physiology and function than previously reported.

Shi|Liheng|L|
Chang|Janet Ya-An|JY|
Yu|Fei|F|
Ko|Michael L|ML|
Ko|Gladys Y-P|GY|

L-type voltage-gated calcium channel
photoreceptor
electroretinogram
ribbon synapses


Edible bird's nest attenuates procoagulation effects of high-fat diet in rats.

Abstract: Edible bird's nest (EBN) is popular in Asia, and has long been used traditionally as a supplement. There are, however, limited evidence-based studies on its efficacy. EBN has been reported to improve dyslipidemia, which is closely linked to hypercoagulation states. In the present study, the effects of EBN on high-fat diet- (HFD-) induced coagulation in rats were evaluated. Rats were fed for 12 weeks with HFD alone or in combination with simvastatin or EBN. Food intake was estimated, and weight measurements were made during the experimental period. After sacrifice, serum oxidized low-density lipoprotein (oxLDL), adiponectin, leptin, von willibrand factor, prostacyclin, thromboxane and lipid profile, and whole blood coagulation indices (bleeding time, prothrombin time, activated partial thromboplastin time, red blood count count, and platelet count) were estimated. Furthermore, hepatic expression of coagulation-related genes was evaluated using multiplex polymerase chain reaction. The results indicated that EBN could attenuate HFD-induced hypercholesterolemia and coagulation similar to simvastatin, partly through transcriptional regulation of coagulation-related genes. The results suggested that EBN has the potential for lowering the risk of cardiovascular disease-related hypercoagulation due to hypercholesterolemia.

Yida|Zhang|Z|
Imam|Mustapha Umar|MU|
Ismail|Maznah|M|
Ismail|Norsharina|N|
Hou|Zhiping|Z|

D060885:Multiplex Polymerase Chain Reaction

high-fat diet
coagulation
hypercholesterolemia
edible bird’s nest
nutrigenomics


Effects of surface reflectance on local second order shape estimation in dynamic scenes.

Abstract: In dynamic scenes, relative motion between the object, the observer, and/or the environment projects as dynamic visual information onto the retina (optic flow) that facilitates 3D shape perception. When the object is diffusely reflective, e.g. a matte painted surface, this optic flow is directly linked to object shape, a property found at the foundations of most traditional shape-from-motion (SfM) schemes. When the object is specular, the corresponding specular flow is related to shape curvature, a regime change that challenges the visual system to determine concurrently both the shape and the distortions of the (sometimes unknown) environment reflected from its surface. While human observers are able to judge the global 3D shape of most specular objects, shape-from-specular-flow (SFSF) is not veridical. In fact, recent studies have also shown systematic biases in the perceived motion of such objects. Here we focus on the perception of local shape from specular flow and compare it to that of matte-textured rotating objects. Observers judged local surface shape by adjusting a rotation and scale invariant shape index probe. Compared to shape judgments of static objects we find that object motion decreases intra-observer variability in local shape estimation. Moreover, object motion introduces systematic changes in perceived shape between matte-textured and specular conditions. Taken together, this study provides a new insight toward the contribution of motion and surface material to local shape perception.

Dövencioğlu|Dicle N|DN|
Wijntjes|Maarten W A|MW|
Ben-Shahar|Ohad|O|
Doerschner|Katja|K|

Shape from specular flow
Surface materials
Shape from motion


Baroreflex failure increases the risk of pulmonary edema in conscious rats with normal left ventricular function.

Abstract: In heart failure with preserved ejection fraction (HFpEF), the complex pathogenesis hinders development of effective therapies. Since HFpEF and arteriosclerosis share common risk factors, it is conceivable that stiffened arterial wall in HFpEF impairs baroreflex function. Previous investigations have indicated that the baroreflex regulates intravascular stressed volume and arterial resistance in addition to cardiac contractility and heart rate. We hypothesized that baroreflex dysfunction impairs regulation of left atrial pressure (LAP) and increases the risk of pulmonary edema in freely moving rats. In 15-wk Sprague-Dawley male rats, we conducted sinoaortic denervation (SAD, n = 6) or sham surgery (Sham, n = 9), and telemetrically monitored ambulatory arterial pressure (AP) and LAP. We compared the mean and SD (lability) of AP and LAP between SAD and Sham under normal-salt diet (NS) or high-salt diet (HS). SAD did not increase mean AP but significantly increased AP lability under both NS (P = 0.001) and HS (P = 0.001). SAD did not change mean LAP but significantly increased LAP lability under both NS (SAD: 2.57 ± 0.43 vs. Sham: 1.73 ± 0.30 mmHg, P = 0.01) and HS (4.13 ± 1.18 vs. 2.45 ± 0.33 mmHg, P = 0.02). SAD markedly increased the frequency of high LAP, and SAD with HS prolonged the duration of LAP > 18 mmHg by nearly 20-fold compared with Sham (SAD + HS: 2,831 ± 2,366 vs. Sham + HS: 148 ± 248 s, P = 0.01). We conclude that baroreflex failure impairs volume tolerance and together with salt loading increases the risk of pulmonary edema even in the absence of left ventricular dysfunction. Baroreflex failure may contribute in part to the pathogenesis of HFpEF.

Sakamoto|Kazuo|K| Hosokawa|Kazuya|K| Saku|Keita|K| Sakamoto|Takafumi|T| Tobushi|Tomoyuki|T| Oga|Yasuhiro|Y| Kishi|Takuya|T| Ide|Tomomi|T| Sunagawa|Kenji|K|


Inferring cost of transport from whole-body kinematics in three sympatric turtle species with different locomotor habits.

Abstract: Chelonians are mechanically unusual vertebrates as an exoskeleton limits their body wall mobility. They generally move slowly on land and have aquatic or semi-aquatic lifestyles. Somewhat surprisingly, the limited experimental work that has been done suggests that their energetic cost of transport (CoT) are relatively low. This study examines the mechanical evidence for CoT in three turtle species that have differing degrees of terrestrial activity. Our results show that Apolone travels faster than the other two species, and that Chelydra has higher levels of yaw. All the species show poor mean levels of energy recovery, and, whilst there is considerable variation, never show the high levels of energy recovery seen in cursorial quadrupeds. The mean mechanical CoT is 2 to 4 times higher than is generally seen in terrestrial animals. We therefore find no mechanical support for a low CoT in these species. This study illustrates the need for research on a wider range of chelonians to discover whether there are indeed general trends in mechanical and metabolic energy costs.

Sellers|William I|WI|
Rose|Kayleigh A R|KAR|
Crossley|Dane A|DA|
Codd|Jonathan R|JR|

Kinematics
Energy recovery
Biomechanics
Walking


Antiprotozoal Nor-Triterpene Alkaloids from Buxus sempervirens L.

Abstract: Malaria and human African trypanosomiasis (HAT; sleeping sickness) are life-threatening tropical diseases caused by protozoan parasites. Due to limited therapeutic options, there is a compelling need for new antiprotozoal agents. In a previous study, O-tigloylcyclovirobuxeine-B was recovered from a B. sempervirens L. (common box; Buxaceae) leaf extract by bioactivity-guided isolation. This nor-cycloartane alkaloid was identified as possessing strong and selective in vitro activity against the causative agent of malaria tropica, Plasmodium falciparum (Pf). The purpose of this study is the isolation of additional alkaloids from B. sempervirens L. to search for further related compounds with strong antiprotozoal activity. In conclusion, 25 alkaloids were obtained from B. sempervirens L., including eight new natural products and one compound first described for this plant. The structure elucidation was accomplished by UHPLC/+ESI-QqTOF-MS/MS and NMR spectroscopy. The isolated alkaloids were tested against Pf and Trypanosoma brucei rhodesiense (Tbr), the causative agent of East African sleeping sickness. To assess their selectivity, cytotoxicity against mammalian cells (L6 cell line) was tested as well. Several of the compounds displayed promising in vitro activity against the pathogens in a sub-micromolar range with concurrent high selectivity indices (SI). Consequently, various alkaloids from B. sempervirens L. have the potential to serve as a novel antiprotozoal lead structure.

nor-cycloartane alkaloids
antiprotozoal activity
structure elucidation
Buxus sempervirens L.
natural product isolation


Remote Pediatric Ophthalmology and Adult Strabismus during the COVID-19 Pandemic.

Abstract:
BACKGROUND
The coronavirus (COVID-19) global pandemic has been a poignant reminder of the value of telehealth services to deliver care, especially as a means of reducing the risk of infectious disease transmission caused by close personal contact, decreasing unnecessary travel for medical consultations, and limiting the number of individuals in waiting rooms. The role of telehealth in ophthalmology has historically been limited to store-and-forwarding of images, much like what is used in radiology.

PATIENTS AND METHODS
Remote evaluation using two-way audio-video communications over the initial 10-week period of clinic shutdowns. Visual acuity (VA) measurement was attempted using a printed single surrounded HOTV or Snellen chart. The VA measurement of fellow eyes was compared to the prior in person clinical visit. External and strabismus examinations were also conducted.

RESULTS
Fifty-eight patients were evaluated with a mean age 12.5 years (range 5 months to 82 years). Twenty of 58 (34%) were younger than 5 years of age. Reasons for evaluation were strabismus in 26 patients (45%), refractive error in 25 (43%), and amblyopia in 10 patients (19%). Recognition visual acuity was obtained in 69% (40 of 58), including every patient older than 5 years of age. Nine children from 2 to 5 years of age (mean 3 years) were unable to perform HOTV VA testing. Of nine children unable to do complete VA testing, five had been premature and seven had developmental delay. There was a mean bias of -0.12 logMAR in favor of the prior in office test in the right eyes of 21 non-amblyopic patients. The 95% limits of agreement between the in-person visit and the subsequent telehealth video visit logMAR VA were +0.20 logMAR upper limit, -0.44 logMAR lower limit.

CONCLUSIONS
Telehealth video visits provided basic ophthalmic information in patients who are physically incapable to come to the office, leading to improved triage. Vision could be tested remotely in young children, but we found substantial variability in the measurement of clinically normal eyes. Improvements in the reliability of at-home visual acuity testing are needed.

Christoff|Alex|A|
Guo|Xinxing|X|
Repka|Michael X|MX|

COVID-19 coronavirus telehealth telemedicine


Effect of dark discolouration and enamel/dentine fracture on the oral health-related quality of life of pre-schoolers.

Abstract:
AIM
To determine the effect of different types of dental trauma on oral health-related quality of life (OHRQoL) among pre-school children.

METHODS
Four hundred fifty-nine Brazilian pre-schoolers aged 3-5 years were submitted to an oral examination in the school environment for the evaluation of dental trauma using the criteria proposed by Andreasen et al. (2007). Parents answered a questionnaire on the OHRQoL of the children using the Early Childhood Oral Health Impact Scale (ECOHIS) and another one on socio-demographic characteristics of the children and their families. The questionnaires were sent to the parents to be answered at home. Descriptive statistics, Mann-Whitney test and Poisson regression were used for statistical analysis.

RESULTS
Children with dark discolouration and enamel-dentine fracture without pulp exposure had higher mean ECOHIS scores than those without these alterations. The multivariate regression analysis demonstrated that pre-school children with dark discolouration (PR 1.79; 95% CI 1.24-2.58) and enamel-dentine fracture without pulp exposure (PR 1.89; 95% CI 1.22-2.92) had a higher impact on quality of life than those without these alterations.

CONCLUSION
Dark discolouration and enamel-dentine fracture without pulp exposure were associated with a negative impact on the life of pre-schoolers.

Ramos-Jorge|J|J|
Sá-Pinto|A C|AC|
Almeida Pordeus|I|I|
Martins Paiva|S|S|
Castro Martins|C|C|
Ramos-Jorge|M L|ML|

Quality of life
Pre-school children
Incisor
Tooth injuries


Suboptimal Response to Coronavirus Disease 2019 Messenger RNA Vaccines in Patients With Hematologic Malignancies: A Need for Vigilance in the Postmasking Era.

Abstract: We measured severe acute respiratory syndrome coronavirus 2 immunoglobulin G responses in 67 patients with hematological malignancies after 2 messenger RNA vaccine doses. Forty-six percent were nonresponders; patients with B-cell chronic lymphocytic leukemia were at highest risk (77% nonresponders). Patients with hematological malignancies should continue wearing masks and socially distancing. Studies of revaccination, boosters, and humoral immune correlates of protection are needed.

Agha|Mounzer E|ME|
Blake|Maggie|M|
Chilleo|Charles|C|
Wells|Alan|A|
Haidar|Ghady|G|

hematological malignancy
2
19 vaccine
COVID
CoV
SARS
antibody


Protective effect of resveratrol against neuronal damage following transient global cerebral ischemia in mice.

Abstract: Resveratrol (3,5,4'-trihydroxystilbene) is a natural polyphenol which is rich in grape seeds and skin. Several studies have revealed that resveratrol possesses neuroprotective effects. In the case of global brain ischemia, there are few reports regarding the protective effect of resveratrol. Therefore, the influence of resveratrol on neuronal damage after transient global brain ischemia remains to be clarified. In the current study, C57BL/6 black mice were subjected to 20 min of transient global brain ischemia and followed by 72 h of reperfusion. Resveratrol (20 or 40 mg/kg, once daily, dissolved in 0.5% carboxymethylcellulose) was administered orally for 7 days before ischemia and daily until the mice were euthanized. The effect of lower or higher dose of resveratrol on neuronal damage, matrix metalloproteinase (MMP) activity and in situ DNA fragmentation (TUNEL) assay in the hippocampus after global ischemia was examined. Neuronal damages were remarkable in CA1 and CA2 pyramidal cell layers after global ischemia. In resveratrol-treated mice (40 mg/kg), neuronal damage was significantly reduced compared with vehicle-treated mice. Mice treated with resveratrol showed reduced MMP-9 activity. Resveratrol also inhibited TUNEL staining. These data suggest that resveratrol, a natural polyphenol, reduces hippocampal neuronal cell damage following transient global ischemia by reducing MMP-9 activity.

Resveratrol
Neuronal damage
Global brain ischemia
Matrix metalloproteinase
Hippocampus


Serum tryptase concentration and progression to end-stage renal disease.

Abstract:
BACKGROUND
Mast cell activation can lead to nonclassical activation of the Renin-Angiotensin-Aldosterone System. However, the relevance of this to human chronic kidney disease is unknown. We assessed the association between serum tryptase, a product of mast cell activation, and progression to end-stage renal disease or mortality in patients with advanced chronic kidney disease. We stratified patients by use of angiotensin-converting enzyme inhibitors/angiotensin receptor II blockers (ACEi/ARB).

MATERIALS AND METHODS
This was a prospective cohort study of 446 participants recruited into the Renal Impairment in Secondary Care study. Serum tryptase was measured at recruitment by sandwich immunoassay. Cox regression analysis was undertaken to determine variables associated with progression to end-stage renal disease or death.

RESULTS
Serum tryptase concentration was independently associated with progression to end-stage renal disease but not with death. In patients treated with ACEi or ARB, there was a strong independent association between higher tryptase concentrations and progression to end-stage renal disease; when compared to the lowest tertile, tryptase concentrations in the middle and highest tertiles had hazard ratios [HR] of 5·78 (95% confidence interval [CI] 1·19-28·03, P = 0·029) and 6·19 (95% CI 1·49-25·69, P = 0·012), respectively. The other independent risk factors for progression to end-stage renal disease were lower age, male gender, lower estimated glomerular filtration rate and higher urinary albumin creatinine ratio.

CONCLUSION
Elevated serum tryptase concentration is an independent prognostic factor for progression to end-stage renal disease in patients with chronic kidney disease who are receiving treatment with an ACEi or ARB.

Jesky|Mark D|MD|
Stringer|Stephanie J|SJ|
Fenton|Anthony|A|
Ng|Khai Ping|KP|
Yadav|Punit|P|
Ndumbo|Miguel|M|
McCann|Katerina|K|
Plant|Tim|T|
Dasgupta|Indranil|I|
Harding|Stephen J|SJ|
Drayson|Mark T|MT|
Redegeld|Frank|F|
Ferro|Charles J|CJ|
Cockwell|Paul|P|

end-stage renal disease
Chronic kidney disease
risk factors
mortality risk
progression of renal failure


Outcome Improvement Between the First Two Waves of the Coronavirus Disease 2019 Pandemic in a Single Tertiary-Care Hospital in Belgium.

Abstract:
Objectives
To compare patient management and outcome during the first and second waves of the coronavirus 2019 pandemic.

Design
Single-center prospective cohort study.

Setting
Tertiary-care University Hospital.

Patients
All adult patients admitted in either the first (from March 15 to May 15, 2020) or second (from October 1 to November 30, 2020) wave of coronavirus disease 2019.

Interventions
None.

Measurements and Main Results
Primary outcome was 30-day mortality. During the second wave of the coronavirus disease 2019 pandemic, 33 patients (4.8%) were transferred due to overcrowding and excluded from analysis. There were 341 (first wave of the coronavirus disease 2019 pandemic) and 695 (second wave of the coronavirus disease 2019 pandemic) coronavirus disease 2019 patients admitted to the hospital, with median age first wave of the coronavirus disease 2019 pandemic as 68 (57-80) and second wave of the coronavirus disease 2019 pandemic as 71 (60-80) (p = 0.15), and similar admission severity. For the first wave of the coronavirus disease 2019 pandemic versus second wave of the coronavirus disease 2019 pandemic, 30-day mortality was 74/341 (22%) and 98/662 (15%) (p = 0.007). In the ward, 11/341 (3.2%) and 404/662 (61%) received dexamethasone (p < 0.001); 6/341 (2%) and 79/662 (12%) received high-flow nasal oxygen (p < 0.0001); 2/341 (0.6%) and 88/662 (13.3%) received remdesivir (p < 0.0001); 249/341 (73%) and 0/662 (0%) received hydroxychloroquine (p < 0.0001); and 87/341 (26%) and 128/662 (19%) (p = 0.024) patients were transferred to ICU. On ICU admission, median Sequential Organ Failure Assessment was 6 (3-7) and 4 (3-6) (p = 0.02). High-flow nasal oxygen was given to 16/87 (18%) and 102/128 (80%) (p < 0.001); 69/87 (79%) and 56/128 (44%) received mechanical ventilation (p < 0.001) with durations 17 days (10-26 d) and 10 days (5-17 d) (p = 0.01). Median ICU length of stay was 14 days (5-27 d) and 6 days (3-11 d) (p < 0.001). Finally, 16/87 (18%) and 8/128 (6%) received renal replacement therapy (p = 0.0055); and 64/87 (74%) and 51/128 (40%) needed vasopressor support (p < 0.001).

Conclusions
The main therapeutic changes between the first wave of the coronavirus disease 2019 pandemic and the second wave of the coronavirus disease 2019 pandemic were use of steroids, unrestrictive use of high-flow nasal oxygen for hypoxemic patients, and transfer of patients to other geographic areas in the case of ICU overcrowding. These changes were associated with a decrease in 30-day mortality, ICU admission, and organ support.

Lambermont|Bernard|B|
Rousseau|Anne-Françoise|AF|
Seidel|Laurence|L|
Thys|Marie|M|
Cavalleri|Jonathan|J|
Delanaye|Pierre|P|
Chase|J Geoffrey|JG|
Gillet|Pierre|P|
Misset|Benoit|B|

coronavirus disease 2019
high-flow nasal oxygen
remdesivir
mechanical ventilation
corticosteroids
intensive care


Polydrug Use and Co-occurring Substance Use Disorders in a Respondent Driven Sampling of Cocaine Base Paste Users in Santiago, Chile.

Abstract: We characterized substance use patterns and co-occurring substance use disorders among active cocaine base paste (CBP) users in Santiago, Chile using data from respondent-driven sampling (RDS) in three areas of Metropolitan Santiago. Recruitment began with nine seeds, reaching 398 active CBP users (18% women; mean age 37.7 years), defined as persons consuming CBP at least twice per week in the last three months. Population proportions and uncertainty were estimated accounting for individuals' social network and homophily. The median CBP age of initiation was 21 years, and the median number of years using CBP was 7 for women and 15 for men. The median days of use in the past month was 25 days, with a median of 56 doses per week. The proportion of monthly income spent on CBP was 65%. The prevalence of substance use disorders (SUDs) were: 98% for CBP, 67% for alcohol, 60% for marijuana, and 41% for cocaine hydrochloride. Heavy polydrug use patterns and co-occurring SUDs are frequent among active CBP users in the metropolitan area of Santiago. Traditional surveillance strategies may have underestimated polysubstance use and co-occurring SUDs in active CBP users. RDS proved to be a feasible methodology that could be effectively used for substance use surveillance among hard-to-reach populations.

substance use disorder
Chile
respondent-driven sampling
surveillance
Smoked cocaine


The Bariatric Surgery Is Associated with a Lower Incidence of Malignancy: Real World Data from Taiwan.

Abstract:
PURPOSE
This study assessed the benefits and efficacy of bariatric surgery (BS) in reducing the risk of cancer in Asians with morbid obesity.

METHODS
Records for patients aged between 18 and 55 years whose diagnoses corresponded with the ICD-9 codes for obesity and BS were extracted from the National Health Insurance Research Database (NHIRD) in Taiwan between 2000 and 2015. The patients who underwent BS (BS group), those who did not undergo BS (NS group), and the general population (GP group) were propensity score matched. The outcome was newly diagnosed malignancy. Data were extracted from the Registry for Catastrophic Illness Patient Database (RCIPD) of the NHIRD.

RESULTS
The BS group developed significantly less malignancy (1.18%) than the GP group (1.46%, p = 0.0364). There was no statistically significant difference in malignancy risk between the BS and GP groups (aHR =1.00, p = 0.9997). The NS group developed significantly higher malignancy (2.48%) than the GP group (1.97%, p < 0.0001). There was a significantly higher malignancy risk in the NS group (aHR =1.22, p < 0.0001) than in the GP group. In the subgroup analysis, the malignancy risks of the NS group were significantly higher in the subgroup of men aged between 18 and 35 years (aHR =1.37, p = 0.003) and women aged between 18 and 35 years (aHR = 1.62, p < 0.0001), and 35-55 years (aHR = 1.27, p < 0.0001). All the subgroup analyses between the BS and GP groups demonstrated no significant differences.

CONCLUSIONS
Our study demonstrated that BS reduced the risk of malignancy in patients with morbid obesity, particularly in women and young men.

Kao|Yi-Kai|YK| Lin|Hung-Yu|HY| Chen|Chih-I|CI| Su|Yu-Chieh|YC| Chen|Jian-Han|JH|0000-0001-7360-2238

Bariatric surgery
Real world data
Cancer
Obesity


Characterization and nanomechanical properties of novel dental implant coatings containing copper decorated-carbon nanotubes.

Abstract: Fluorapatite-titania coated Ti-based implants are promising for using in dental surgery for restoring teeth. One of the challenges in implantology is to achieve a bioactive coating with appropriate mechanical properties. In this research, simple sol-gel method was developed for synthesis of fluorapatite-titania-carbon nanotube decorated with antibacterial agent. Triethyl phosphate [PO4(C2H5)3], calcium nitrate [Ca(NO3)2] and ammonium fluoride (NH4F) were used as precursors under an ethanol-water based solution for fluorapatite (FA) production. Titanium isopropoxide and isopropanol were used as starting materials for making TiO2 sol-gels. Also, Copper acetate [Cu(C2H3O2)2·H2O] was used as precursor for decoration of multi walled carbon nanotubes (MWCNTs) with wet chemical method. The decorated MWCNTs (CNT(Cu)) were evaluated by transmission electron microscopy (TEM). The phase identification of the FA-TiO2-CNT(Cu) coating was carried out by XRD analysis. Morphology of coated samples was investigated by SEM observations. The surface elastic modulus and hardness of coatings were studied using nanoindentation technique. The results indicate that novel dental implant coating containing FA, TiO2 and copper decorated MWCNTs have proper morphological features. The results of nanoindentation test show that incorporation of CNT(Cu) in FA-TiO2 matrix can improve the nanomechanical properties of composite coating.

Sasani|N|N|
Vahdati Khaki|J|J|
Mojtaba Zebarjad|S|S|

Nanomechanical properties
Fluorapatite
Carbon nanotube
Copper decorated
Sol–gel
Titania


Neurology Education for Critical Care Fellows Using High-Fidelity Simulation.

Abstract:
BACKGROUND
Simulation is becoming a more common modality in medical education. The data regarding effectiveness of simulation in critical care neurology education are limited.

METHODS
We administered a three-scenario simulation course to critical care fellowship trainees at a large academic medical center as a part of their core curriculum requirement. Pre- and posttests assessing medical knowledge and trainee confidence in managing neurologic disease were completed by all trainees. Overall satisfaction and effectiveness were evaluated following the course. Change in trainee knowledge and confidence before and after the course was assessed for improvement.

RESULTS
Sixteen trainees completed the simulation course. Prior to completion, medical knowledge was 5.2 ± 0.9 (of 8 possible correct answers) and following the course was 6.4 ± 1.3 (p = 0.002). Overall confidence improved from 15.4 ± 4.9 (of 30 possible points) to 20.7 ± 3.3 (p = <0.0001). Confidence was significantly improved for neurologic diseases directly assessed during the course (p = <0.0001) as well as for those not directly assessed (p = 0.004).

CONCLUSIONS
Simulation is an effective means of neurologic education for critical care trainees, with improvement in both medical knowledge and trainee confidence after completion of a three-scenario simulation experience. This course ensures the exposure of critical care trainees to neurologic diseases that are required curricular milestones to successfully complete the fellowship training program.

Braksick|Sherri A|SA|
Kashani|Kianoush|K|
Hocker|Sara|S|

D002983:Clinical Competence
D003422:Critical Care
D005257:Fellowships and Scholarships
D006801:Humans
D007396:Internship and Residency
D009462:Neurology
D000066908:Simulation Training

Neurology
Critical care
Simulation
Medical education
Neurologic emergency


Diagnosis, Incidence, and Clinical Implications of Perioperative Myocardial Injury in Vascular Surgery.

Abstract:
INTRODUCTION
Routine measurement of cardiac biomarkers such as troponin T (TnT) is recommended perioperatively, especially in high-risk vascular surgery. Long-term prognosis is worse even in those with nonspecific perioperative myocardial injury. However, a clear understanding of these biomarker profiles and how they should affect patient management is lacking.

METHODS
We examined the perioperative profile of high-sensitivity TnT (hsTnT) release in 85 patients undergoing elective major vascular surgery. Plasma hsTnT was measured preoperatively, at 6, 12, and 24 hours postoperatively, and then every 24 hours for a maximum of 5 days. Significant elevations in hsTnT with/without clinical indicators of ischemia were used to diagnose myocardial infarction or injury.

RESULTS
A high incidence of myocardial injury was evident (46% had elevated hsTnT); only 5% were associated with myocardial infarction, and 41% were due to myocardial injury.

CONCLUSIONS
This study emphasizes the high incidence of perioperative myocardial injury and stress in vascular surgery as revealed by the use of the robust and very sensitive biomarker of myocardial damage, hsTnT. The high availability and swift development of increasingly sensitive assays allow detection of abnormal elevated hsTnT levels in a higher proportion of the population. Consequent challenges are the reduced specificity to separate acute events as well as to deduce the prognostic value of elevations due to confusing criteria; this is especially the case in a patient group with multiple comorbidities that affect hsTnT levels chronically.

Thomas|Kate N|KN|
Cotter|James D|JD|
Williams|Michael J A|MJ|
van Rij|André M|AM|


Conformable fractional Dirac system on time scales.

Abstract: We study the conformable fractional (CF) Dirac system with separated boundary conditions on an arbitrary time scale [Formula: see text]. Then we extend some basic spectral properties of the classical Dirac system to the CF case. Eventually, some asymptotic estimates for the eigenfunction of the CF Dirac eigenvalue problem are obtained on [Formula: see text]. So, we provide a constructive procedure for the solution of this problem. These results are important steps to consolidate the link between fractional calculus and time scale calculus in spectral theory.

Dirac system
time scale
conformable fractional derivative


Baseline Perfusion Alterations Due to Acute Application of Quetiapine and Pramipexole in Healthy Adults.

Abstract:
BACKGROUND
The dopaminergic system is implicated in many mental processes and neuropsychiatric disorders. Pharmacologically, drugs with dopamine receptor antagonistic and agonistic effects are used, but their effects on functional brain metabolism are not well known.

METHODS
In this randomized crossover, placebo-controlled, and rater-blinded study, 25 healthy adults received an acute dose placebo substance (starch), quetiapine (dopamine receptor antagonist), or pramipexole (dopamine agonist of the nonergoline class) 1 hour before the experiment. Background-suppressed 2D pseudo-continuous arterial spin labeling was used to examine whole-brain baseline cerebral blood flow differences induced by the 3 substances.

RESULTS
We found that quetiapine reduced perfusion in the occipital (early visual areas) and bilateral cerebellar cortex relative to placebo. In contrast, quetiapine enhanced cerebral blood flow (relative to placebo) in the striatal system (putamen and caudate nucleus) but also in the supplementary motor area, insular-, prefrontal- as well as in the pre- and postcentral cortex. Pramipexole increased cerebral blood flow compared with placebo in the caudate nucleus, putamen, middle frontal, supplementary motor area, and brainstem (substantia nigra), but reduced cerebral blood flow in the posterior thalamus, cerebellum, and visual areas. Pramipexole administration resulted in stronger cerebral blood flow relative to quetiapine in the hypothalamus, cerebellum, and substantia nigra.

CONCLUSIONS
Our results indicate that quetiapine and pramipexole differentially modulate regional baseline cerebral blood flow. Both substances act on the dopaminergic system, although they affect distinct regions. Quetiapine altered dopaminergic function in frontal, striatal, and motor regions. In contrast, pramipexole affected cerebral blood flow of the nigrostriatal (striatum and substantia nigra) dopaminergic, but less the fronto-insular system.

Michels|Lars|L|
Scherpiet|Sigrid|S|
Stämpfli|Philipp|P|
Herwig|Uwe|U|
Brühl|Annette B|AB|

quetiapine
pramipexole
dopamine agonist
arterial spin labeling
cerebral blood flow
dopamine antagonist


Demonstration of real-time and accelerated stability of hepatitis E vaccine with a combination of different physicochemical and immunochemical methods.

Abstract: Hepatitis E, which is caused by infection with hepatitis E virus (HEV), is a global health problem in both developed and developing countries. An efficacious hepatitis E vaccine was licensed (by China) in 2011 with a trade name of Hecolin®. The antigen contained in this vaccine is a truncated version of the sole capsid protein encoded by open reading frame 2, which is designated p239. In this study, the real-time and real-condition stability and accelerated stability of five lots of hepatitis E vaccine products at the end of the designated shelf life, were assessed by a well-established quality analysis platform. The protein integrity of p239 that was recovered from the vaccine lots was demonstrated using CE-SDS, LC-MS and MALDI-TOF MS. The particle characteristics of the recovered vaccine antigen were assessed by TEM and HPSEC. The immunogenicity of hepatitis E vaccines was assessed by a mouse potency assay, which is part of product release and stability testing. Several methods were employed to assess the antigenicity of vaccines with or without adjuvant dissolution. Specifically, the well-established methods of sandwich ELISA and surface plasma resonance (SPR)-based BIAcore were used with unique murine monoclonal antibodies. Most interesting, two 'dissolution-free' immunoassays were also used for in situ antigenicity assessment of the vaccines. In addition to the confirmation of vaccine stability at the end of expiry dating, i.e., after storage in recommended conditions (2-8 °C) for 36 months, the mouse potency assay and sandwich ELISA were used to assess the accelerated stability of prefilled syringes to demonstrate the feasibility of out-of-cold-chain storage. In summary, molecular and functional characterization confirmed the shelf life stability of the vaccine at the end of expiry dating and the feasibility of transporting the hepatitis E vaccine for a given period of time out of cold chains.

Yin|Xiaochen|X| Wang|Xin|X| Zhang|Zhigang|Z| Li|Yufang|Y| Lin|Zhijie|Z| Pan|Huirong|H| Gu|Ying|Y| Li|Shaowei|S| Zhang|Jun|J| Xia|Ningshao|N| Zhao|Qinjian|Q|

D000818:Animals
D004355:Drug Stability
D004356:Drug Storage
D005240:Feasibility Studies
D005260:Female
D006508:Hepatitis Antibodies
D018963:Hepatitis Antigens
D016751:Hepatitis E
D016752:Hepatitis E virus
D006801:Humans
D007118:Immunoassay
D000071497:Immunogenicity, Vaccine
D051379:Mice
D023421:Models, Animal
D013696:Temperature
D013997:Time Factors
D014614:Vaccines, Synthetic
D014761:Viral Hepatitis Vaccines

Hepatitis E vaccine
Immunochemical methods
Potency assays
Monoclonal antibody
High content analysis
Virus-like particles


FAB: First UK feasibility trial of a future randomised controlled trial of Family focused treatment for Adolescents with Bipolar disorder.

Abstract:
BACKGROUND
This first mixed-methods UK trial examined the feasibility and acceptability of a future definitive randomised controlled trial (RCT) to evaluate whether Family Focussed Treatment for Adolescents with Bipolar Disorder (FFT-A) UK version can improve family functioning and well-being as part of the management of Paediatric Bipolar Disorder (PBD).

METHOD
The trial used a randomised, parallel group, non-blinded design where participants received FFT-A UK (16 sessions over 6 months) immediately or after 12 months (delayed arm). Measures of family functioning, well-being and quality of life of the young person and the main carer (most commonly a parent) were completed at baseline, 6 and 12-months in both arms. Primary outcome measures included rates of eligibility, consent and retention along with estimates of variability in the measures and assessment of the intervention delivery. Qualitative interviews allowed assessment of participants' views about FFT-A and the trial processes.

RESULTS
Twenty-seven of 36 young persons with PBD and their families consented; of these, 14 families were randomised to the immediate and 13 to the delayed arm. Two families from the immediate arm withdrew consent and discontinued participation. Quantitative measures were completed by 22 families (88%) at 6-months and 21 families (84%) at 12-months. Qualitative interviews were conducted with 30 participants (9 young people, 15 parents and 6 other family members). Nine families attended 3 post-trial focus groups.

CONCLUSION
It was feasible to recruit and retain to this trial. The results highlighted that trial design and measures were acceptable to participants. A benefit in family relationships was reported by participants which they attributed to the intervention in qualitative interviews. Families recommended that future modifications include definitive trial(s) recruiting participants in the age range 15-25 years as it felt this was the age range with maximum need. Trial registration ISRCTN, ISRCTN59769322. Registered 20 January 2014, http://www.isrctn.com/ISRCTN59769322.

Adolescent
Bipolar Disorder
Randomized controlled trial


Suicide Attempters, Suicide Ideators, and Non-Ideators.

Abstract: Background: Suicide ideation is a prerequisite for suicide attempts. However, the majority of ideators will never act on their thoughts. It is therefore crucial to understand factors that differentiate those who consider suicide from those who make suicide attempts. Aim: Our aim was to investigate the role of protective factors in differentiating non-ideators, suicide ideators, and suicide attempters. Method: Inpatients without suicide ideation (n = 32) were compared with inpatients with current suicide ideation (n = 37) and with inpatients with current suicide ideation and a lifetime history of suicide attempts (n = 26) regarding positive mental health, self-esteem, trust in higher guidance, social support, and reasons for living. Results: Non-ideators reported more positive mental health, social support, reasons for living, and self-esteem than suicide ideators and suicide attempters did. No group differences were found regarding trust in higher guidance. Suicide ideators and suicide attempters did not differ regarding any of the study variables. Limitations: Results stem from a cross-sectional study of suicide attempts; thus, neither directionality nor generalizability to fatal suicide attempts can be determined. Conclusion: Various protective factors are best characterized to distinguish ideators from nonsuicidal inpatients. However, the same variables seem to offer no information about the difference between ideators and attempters.

Teismann|Tobias|T| Paashaus|Laura|L| Siegmann|Paula|P| Nyhuis|Peter|P| Wolter|Marcus|M| Willutzki|Ulrike|U|

suicide attempt
suicide ideation
protective factors
ideation-to-action


The microbiome and transfusion in cancer patients.

Abstract: Our microbiota is determined by many variables including ABO blood groups. The microbiota is not only confined to the gut and skin but is also recoverable from blood of healthy donors. The microbiota shape our immune system through cross reactivity with antigens, the expression of direct molecular patterns, the release of cytokines, the effects on nutrients and micronutrients and even through an interplay with epigenetics. It is likely, therefore, that a donor's microbiota could alter the antigenicity of blood and its components and potentially contribute to transfusion-related immune modulation [TRIM]. It could also potentially transmit infections. The recipient's microbiome contributes, on the other hand, to the tolerance to transfused blood, or to the development of transfusion reactions. Cancer patients are a particularly vulnerable population, often immunosuppressed with a significantly altered microbiota. They are more at risk for transmission of "dormant" bacteria via blood transfusion. Furthermore, chemotherapy and radiation induce mucositis that likely results in significant translocation of gut microbiota and abnormal immune reactions to transfused blood. It is therefore relevant to revisit transfusion thresholds and consider transfusion-saving strategies in cancer patients.

Goubran|Hadi|H| Seghatchian|Jerard|J| Radosevic|Julia|J| Ragab|Gaafar|G| Burnouf|Thierry|T|


Anti-Jo-1 myositis and the antiphospholipid syndrome showing right ventricular thrombus: a novel overlap syndrome with atypical presentation.

Abstract: It has long been recognized that patients with myositis and positive anti-Jo1 antibody tend to be associated with interstitial lung disease. Recent studies revealed that such patients may also have fever, Raynaud's phenomenon, mechanic's hand, polyarthralgia, or usually mild, self-limiting, non-erosive or erosive polyarthritis known as antisynthetase syndrome. The hallmark of this disorder is the presence of the autoantibodies that recognize the aminoacyl-tRNA synthetases, which play a critical role in protein synthesis. The most well recognized of the autoantibodies is anti-histidyl (Jo-1). Antisynthetase syndrome cases associated with other autoimmune diseases are rarely reported. We here present a case of antisynthetase syndrome presented with right ventricle thrombus and deep vein thrombosis in the lower limbs. Secondary antiphospholipid syndrome was then diagnosed after a series of examinations. The patient was successfully treated with anticoagulant alone without surgical thrombectomy. Our case revealed that clinical physicians should watch for thrombotic complications when facing patients with antisynthetase syndrome. Medical therapy with anticoagulants alone may be an alternative treatment option in patients with right ventricle thrombus who cannot tolerate surgical thrombectomy.

Wang|Ching-Hsun|CH| Wang|Ning-Chi|NC| Lin|Te-Yu|TY| Chen|Chen-Hung|CH|

Antiphospholipid syndrome
Antisynthetase syndrome
Polymyositis


Long-term outcome and quality of life following emergency surgery for acute aortic dissection type A: a comparison between young and elderly adults.

Abstract:
Objectives
Innovations in surgical techniques and perioperative management have continuously improved survival rates for acute aortic dissection type A (AADA). The aim of our study was to evaluate long-term outcome and quality of life (QoL) after surgery for AADA in elderly patients compared with younger patients.

Methods
We retrospectively evaluated 242 consecutive patients, who underwent surgery for AADA between January 2004 and April 2014. Patients were divided into two groups: those aged 70 years and older (elderly group; n  = 78, mean age, 76 ± 4 years) and those younger than 70 years (younger group; n  = 164, mean age, 56 ± 10 years). QoL was assessed with the Short Form Health Survey Questionnaire (SF-36) 1 year after surgery.

Results
The questionnaire return rate was 91.0%. There were already significant differences noted between the two groups with regard to preoperative risk factors on admission. The clinical presentation with a cardiac tamponade was higher in the elderly group (62.8% vs 47.6%; P  = 0.03). Intraoperatively, complex procedures were more common in the younger group (21.3% vs 5.2%; P  = 0.001). Accordingly, cardiopulmonary bypass and cross-clamping times were significantly longer in the younger group. The operative mortality was similar in both groups (3.8% vs 1.2%; P  = 0.33). In the elderly population, 30-day mortality was higher (21.8% vs 7.9%; P  = 0.003). One-year (72% vs 85%), 3-year (68% vs 84%) and 5-year (63% vs 79%) survival rates were satisfactory for the elderly group, but significantly lower compared with the younger group ( P  = 0.008). The physical component summary score also was similar between the groups (39.14 ± 11.12 vs 39.12 ± 12.02; P  = 0.99). However, the mental component summary score might be slightly higher in the elderly group but not statistically significant (51.61 ± 10.73 vs 48.63 ± 11.25; P  = 0.12).

Conclusions
Satisfactory long-term outcome and the general perception of well-being encourage surgery in selected elderly patients with AADA.

Jussli-Melchers|Jill|J| Panholzer|Bernd|B| Friedrich|Christine|C| Broch|Ole|O| Renner|Jochen|J| Schöttler|Jan|J| Rahimi|Aziz|A| Cremer|Jochen|J| Schoeneich|Felix|F| Haneya|Assad|A|

Quality of life
Acute aortic dissection type A
Elderly


Adsorption and release on three-dimensional graphene oxide network structures.

Abstract: In this study, three-dimensional network architectures are constructed using nano-sized graphene oxide (nGO) as the building block. The cross-linking reaction of nGO is conducted in sub-micrometre water droplets in an emulsion system to control the size of the networks by restricting the reaction space. Two types of three-dimensional GO networks with different cross-linking lengths were constructed, and their methyl orange adsorption and release behaviours were investigated under external stimuli, such as thermal treatment, ultrasonic wave treatment and near-infrared light irradiation.

Kim|Sunnam|S|0000-0001-5039-7569 Moriya|Sho|S| Maruki|Sakura|S| Fukaminato|Tuyoshi|T| Ogata|Tomonari|T| Kurihara|Seiji|S|

graphene oxide
network structure
drug delivery


Radiotherapy target volume definition in newly diagnosed high grade glioma using 18F-FET PET imaging and multiparametric perfusion MRI: A prospective study (IMAGG).

Abstract:
PURPOSE
The aim of this study was to prospectively investigate tumor volume delineation by amino acid PET and multiparametric perfusion magnetic resonance imaging (MRI) in patients with newly diagnosed, untreated high grade glioma (HGG).

MATERIALS AND METHODS
Thirty patients with histologically confirmed HGG underwent O-(2-[18F]-fluoroethyl)-l-tyrosine (18F-FET) positron emission tomography (PET), conventional Magnetic Resonance Imaging (MRI) as contrast-enhanced (CE) and fluid-attenuated inversion recovery (FLAIR) and multiparametric MRI as relative cerebral blood volume (rCBV) and permeability estimation map (K2). Areas of MRI volumes were semi-automatically segmented. The percentage overlap volumes, Dice and Jaccard spatial similarity coefficients (OV, DSC, JSC) were calculated.

RESULTS
The 18F-FET tumor volume was significantly larger than the CE volume (median 43.5 mL (2.5-124.9) vs. 23.8 mL (1.4-80.3), p = 0.005). The OV between 18F-FET uptake and CE volume was low (median OV 0.59 (0.10-1)), as well as spatial similarity (median DSC 0.52 (0.07-0.78); median JSC 0.35 (0.03-0.64)). Twenty-five patients demonstrated both rCBV and CE on MRI: The median rCBV tumor volume was significantly smaller than the median CE volume (p < 0.001). The OV was high (median 0.83 (0.54-1)), but the spatial similarity was low (median DSC 0.45 (0.04-0.83); median JSC 0.29 (0.07-0.71)). Twenty-eight patients demonstrated both K2 and CE on MRI. The median K2 tumor volume was not significantly larger than the median CE volume. The OV was high (median OV 0.90 (0.61-1)), and the spatial similarity was moderate (median DSC 0.75 (0.01-0.83); median JSC 0.60 (0.11-0.89)).

CONCLUSION
We demonstrated that multiparametric perfusion MRI volumes (rCBV, K2) were highly correlated with CE T1 gadolinium volumes whereas 18F-FET PET provided complementary information, suggesting that the metabolically active tumor volume in patients with newly diagnosed untreated HGG is critically underestimated by contrast enhanced MRI. 18F-FET PET imaging may help to improve target volume delineation accuracy for radiotherapy planning.

Dissaux|Gurvan|G|
Dissaux|Brieg|B|
Kabbaj|Osman El|OE|
Gujral|Dorothy M|DM|
Pradier|Olivier|O|
Salaün|Pierre-Yves|PY|
Seizeur|Romuald|R|
Bourhis|David|D|
Ben Salem|Douraied|D|
Querellou|Solène|S|
Schick|Ulrike|U|

Radiotherapy target volume
High grade glioma
Multiparametric perfusion MRI
Tumor volume
(18)F-FET PET
GTV


Cloning, Characterization, and Expression Analysis of Three FAD8 Genes Encoding a Fatty Acid Desaturase from Seeds of Paeonia ostii.

Abstract: The FAD8 gene catalyzes the conversion of diene fatty acids to triene fatty acids and is a key enzyme that determines the synthesis of alpha-linolenic acid. In this study, the full-length cDNAs of FAD8-1, FAD8-2, and FAD8-3 are cloned from Paeonia ostii T. Hong & J. X. Zhang and named as PoFAD8-1, PoFAD8-2, and PoFAD8-3. Their open reading frame is 1203 bp, 1152 bp, and 1353 bp which encoded 400, 371, and 450 amino acids. The molecular weights of the amino acids are 46 kDa, 43 kDa, and 51 kDa while the isoelectric points are 7.34, 8.74, and 9.23, respectively. Bioinformatics analysis shows that all three genes are hydrophobic-hydrophobic, PoFAD8-1 has three transmembrane domains, and PoFAD8-2 and PoFAD8-3 have two transmembrane domains. Multiple series alignment and phylogenetic analysis revealed that PoFAD8-1 and PoFAD8-2 are closely related while PoFAD8-3 is more closely related to Paeonia delavayi. Subcellular localization results showed that PoFAD8-1 was located on the ER membrane and PoFAD8-2 and PoFAD8-3 were located on the chloroplast membrane. The relative expression level of PoFAD8-1 in seeds is very high. PoFAD8-2 expressed more in the ovary than the other two genes. PoFAD8-3 was highly expressed in roots, stems, leaves, petals, and ovaries.

Sun|Jing|J|0000-0002-8658-8305 Chen|Ming|M| Zhu|Mengyuan|M| Jiang|Yu|Y| Meng|Jiasong|J| Zhao|Daqiu|D| Tao|Jun|J|

D018506:Gene Expression Regulation, Plant

D060888:Real-Time Polymerase Chain Reaction

FAD8
Paeonia ostii
bioinformatics
subcellular localization
quantitative real-time PCR


The effect of vocalization on spinal excitation as measured by H wave.

Abstract: The aim of this study was to measure the H wave by using voice-activated electromyography to reveal how different speech outputs affect the spinal cord segments innervating the lower limb skeletal muscles. In 21 healthy adults (16 men and 5 women) seated in a semi-reclined position, the H wave was recorded using surface electrodes over the soleus muscle of the pivot leg after stimulating the tibial nerve. The amplitude of the H wave was 1.02 SD 0.69 mV under the pre-vocalization condition; 1.51 SD 0.76 mV under the submaximal vocalization condition (≥60-<80 dB); and 1.13 SD 0.59 mV under the maximal vocalization condition (≥80 dB), demonstrating that the amplitude generated with submaximal vocalization was significantly higher than the control and maximal vocalization conditions. Mean voice intensity was around 69 dB for submaximal vocalization and around 91 dB for maximal vocalization. Submaximal vocalization results in a higher H wave amplitude than the control condition, thus suggesting increased spinal cord excitation, which may be important for initiating activities of daily living (e.g., lifting objects) or mobility (e.g., moving from a sitting to a standing position).

Furukawa|Katsuhiro|K| Fujiwara|Takayuki|T| Abe|Koji|K| Kamijo|Masayosi|M|

H wave
phonation effect
spinal cord excitability level
therapeutic exercise


Immune System Evasion as Hallmark of Melanoma Progression: The Role of Dendritic Cells.

Abstract: Melanoma is an immunogenic tumor whose relationship with immune cells resident in the microenvironment significantly influences cancer cell proliferation, progression, and metastasis. During melanomagenesis, both immune and melanoma cells undergo the immunoediting process that includes interconnected phases as elimination, equilibrium, and escape or immune evasion. In this context, dendritic cells (DCs) are active players that indirectly counteract the proliferation of melanoma cells. Moreover, DC maturation, migration, and cross-priming as well as their functional interplay with cytotoxic T-cells through ligands of immune checkpoint receptors result impaired. A number of signals propagated by highly proliferating melanoma cells and accessory cells as T-cells, natural killer cells (NKs), tumor-associated macrophages (TAMs), T-regulatory cells (T-regs), myeloid-derived suppressor cells (MDSCs), and endothelial cells participate to create an immunosuppressive milieu that results engulfed of tolerogenic factors and interleukins (IL) as IL-6 and IL-10. To underline the role of the immune infiltrate in blocking the melanoma progression, it has been described that the composition, density, and distribution of cytotoxic T-cells in the surrounding stroma is predictive of responsiveness to immunotherapy. Here, we review the major mechanisms implicated in melanoma progression, focusing on the role of DCs.

Tucci|Marco|M|
Passarelli|Anna|A|
Mannavola|Francesco|F|
Felici|Claudia|C|
Stucci|Luigia Stefania|LS|
Cives|Mauro|M|
Silvestris|Francesco|F|

melanoma
dendritic cells
microenvironment
T-cells
checkpoint inhibitors


COMPARATIVE HYGIENIC ASSESSMENT OF WORKING CONDITIONS AND OCCUPATIONAL RISK IN THE APPLICATION OF PESTICIDES (ON THE EXAMPLE OF FUNGICIDE AMISTAR EXTRA 280, SC) USING DIFFERENT TYPES OF SPRAYERS.

Abstract:
OBJECTIVE
The aim: Was a comparative hygienic assessment of working conditions and occupational risk in the application of fungicide Amistar Extra 280, SC using slotted and injector sprayers.

PATIENTS AND METHODS
Materials and methods: Sprayers Super Poly 110-04 (variant №1) and Guardian Air GA110-04 (variant № 2), and certified equipment were used. The occupational risk was assessed in accordance with the methodological recommendations proposed by the L.I. Medvedia Scientific Center for Preventive Toxicology, Food and Chemical Safety specialists.

RESULTS
Results: When using the slotted sprayer Super Poly 110-04 in the air of the working zone of the tractor driver the content of azoxystrobin was 0.0015 ± 0.0001 mg/m3, cyproconazole - 0.085 ± 0.002 mg/m3, at a distance of 10 m from the edge of the field on the leeward side - 0.003 ± 0.001 and 0.11 ± 0.02 mg/m3, respectively. Visual analysis of water-sensitive cards after using slotted sprayers showed the presence of single drops of pesticide working solution in the wear zone. When applying the pesticide using a Guardian Air GA110-04 injector sprayer in the air of the working zone of the tractor driver, areas of possible wear (10 and 100 m), theconcentration of the active substances of Amistar Extra 280, SC formulation was below the limit of quantification of the method. When assessing the complex risk for tractor drivers, a statistically significant difference was found for azoxystrobin (p = 0.002) and cyproconazole (p = 0.001) when using a slotted sprayer Super Poly 110-04 and injector Guardian Air GA110-04.

CONCLUSION
Conclusions: Values of the combined complex risk of application of the Amistar Extra 280, SC formulation for tractor drivers of variant №2 application were significantly lower than those for tractor drivers of variant №1.

Borysenko|Аndrii А|АА|
Antonenko|Аnna М|АМ|
Omelchuk|Sergii Т|SТ|
Bardov|Vasyl G|VG|
Vavrinevych|Olena P|OP|

complex
combined occupational risk
injector nozzle
type of spraying


Do patients with Ménière's disease have attacks of syncope?

Abstract: The aim of the present study was to evaluate the prevalence and associated factors for syncope among patients with Ménière's disease (MD). An attack of syncope was defined as a sudden and transient loss of consciousness, which subsides spontaneously and without a localizing neurological deficit. The study used an across-sectional survey design. Information from a database consisting of 961 individuals was collected from the Finnish Ménière Association. The data contained case histories, general health-related quality of life (HRQoL), and impact measurements of the complaints. In the current study sample, syncope occurred in 12.3% of the patients with MD. It was more prevalent among elderly persons and among those with a longer duration of MD. Syncope was significantly associated with disturbances of otolith function reflected as Tumarkin attacks, gait and balance problems, environmental change of pressure, and physical strain. It was also associated with visual blurring; in fact, patients with otolith dysfunction in MD often experience visual field changes. It was also associated with headache, but not with migraine. Syncope was experienced as frightening and HRQoL was significantly worsened. The patient had higher anxiety scores, and suffered more from fatigue. The results demonstrate that neurally mediated syncope occurs in patients with an advanced form of MD who suffer from Tumarkin attacks due to failure in otolith function. The mechanism seems to be triggered through the vestibular sympathetic reflex when the otolith system fails due to disrupted utricular otolithic membrane mediate erroneous positional information from the otolith organ to the vasomotor centres in the brain stem and medulla.

Pyykkö|Ilmari|I| Manchaiah|Vinaya|V| Zou|Jing|J| Levo|Hilla|H| Kentala|Erna|E|

Syncope
Tumarkin attacks
Otolith organ
Drop attack
Fainting vestibular disorder
Ménière’s disease


Service Delivery Reforms for Asian Ageing Societies: A Cross-Country Study Between Japan, South Korea, China, Thailand, Indonesia, and the Philippines.

Abstract:
Introduction
Japan's health policies to address the most advanced-aged society have been the target of focus in Asia, but no studies have investigated this issue using tools for cross-country comparisons.

Theory and methods
A cross-country study design was used to compare healthcare reform policies with a framework in Japan, Korea, Thailand, China, Indonesia, and the Philippines. Data were collected via document reviews and key informant interviews.

Results
Three distinctions were identified. First, all countries except for the Philippines have policy decisions regarding reforms for the existing service delivery systems for healthcare, long-term care and welfare. Second, the most extensive service delivery reform is currently being implemented in Japan, whose system is shifting to primary health care. Third, the direction of the transformation of service delivery system is different between Thailand and China despite a similar level of ageing society. China has made progress on facility-based care integration between health and social care, whereas Thailand is focusing on home-based care.

Conclusions and discussion
Doctor and hospital-based healthcare delivery system requires more drastic reform for an aged society. This fact implies that strengthening primary health care is not only useful for current health issues but also an investment for the aged society near future in low- and middle-income countries.

service delivery reforms
ageing societies
healthcare service delivery
integrated care


Homogeneous Group approach to Elixhauser comorbidity for hospital death using administrative data.

Abstract:
Introduction
The purpose of this study was to introduce a measure of patient's burden based on Elixhauser's comorbidity index. The mentioned measure needed to be based solely on administrative data and be applicable to all specialisations of hospital treatment. Moreover, the intention was to validate the estimation power of the models based on the groups of hospitalisations which were similar with respect to the primary diagnosis.

Material and methods
In the study, we considered all hospitalisations in Poland from 2014 and 2015. Overall, 22 045 267 hospitalisation records of 11 566 525 patients were retrieved. An important element of this research was to validate the estimation power of the models based on the groups of patients who were similar with respect to the main reason for hospitalisation. Therefore, the population was split into 21 Homogeneous Groups based on the changed primary diagnosis. As explanatory variables we used demographic variables and 31 comorbidities defined by Elixhauser. The outcome variable was patient's mortality - in-hospital or up to 365 days after discharge.

Results
Out of the 21 created models, 9 had a very good estimation power (C-statistic over 0.85), the other 9 had satysfying results (C-statistic between 0.75 and 0.85) and only 3 performed poorly (C-statistic below 0.75). The odds ratio of variables varied widely between the groups.

Conclusions
Our results support the hypothesis that comorbidity properly describes mortality in homogeneous groups of patients. Our models could be condensed into one, uniform, single-number comorbidity scale that summarizes all of the patient's burden. It was found that the odds ratio of some variables differed between homogeneous groups.

administrative data
mortality
Elixhauser comorbidity index
quality of healthcare
risk adjustment


Determinants of insufficient improvement in fractional flow reserve following percutaneous coronary intervention.

Abstract: Fractional flow reserve (FFR) has become an increasingly important index for decision making concerning coronary revascularization. It is commonly accepted that significant improvement in FFR following percutaneous coronary intervention (PCI) is associated with better symptomatic relief and a lower event rate. However, in lesions with insufficient FFR improvement, PCI may not improve prognosis. Leading to the observation that the clinical and angiographic characteristics associated with insufficient FFR improvement have not been fully explored. The purpose of this study was to investigate the factors associated with insufficient improvement in FFR. Using our own PCI database, established between January 2014 and December 2018, we identified 220 stable coronary artery lesions, which had been evaluated for both pre- and post-PCI FFR values. All 220 of these lesions were included in this study. The improvement in FFR (ΔFFR) was calculated in each lesion with the lowest quartile of ΔFFR being defined as the lowest ΔFFR group, and the other quartiles being defined as the intermediate-high ΔFFR group. The mean ΔFFR in the lowest and intermediate-high ΔFFR groups was 0.07 ± 0.02 and 0.21 ± 0.11, respectively. In multivariate logistic regression analysis, a short total stent length (10 mm increase: OR 0.67, 95% CI 0.47-0.96, P = 0.030), higher pre-PCI FFR (0.1 increase: OR 4.07, 95% CI 1.83-9.06, P = 0.001), in-stent restenosis (ISR) (OR 8.02, 95% CI 1.26-51.09, P = 0.028), myocardial infarction (MI) in the target vessel (OR 6.87, 95% CI 1.19-39.69, P = 0.031) and non-use of intravascular imaging (OR 0.35, 95% CI 0.12-0.99, P = 0.048) were significantly associated with the lowest ΔFFR group. The use of short stents, higher pre-PCI FFR values, ISR, MI in the target vessel, and non-use of intravascular imaging were significantly associated with insufficient FFR improvement. It was conversely suggested that full coverage and adequate dilatation of the lesions under an intravascular imaging guidance might contribute to an improvement in FFR.

D053805:Fractional Flow Reserve, Myocardial

Fractional flow reserve
Percutaneous coronary intervention


Bifid median nerve in carpal tunnel syndrome: do we need to know?

Abstract:
INTRODUCTION
We tested the hypothesis that a bifid median nerve predisposes to development of carpal tunnel syndrome (CTS) and investigated differences in electrophysiological findings and outcome.

METHODS
A total of 259 consecutive patients with clinically defined CTS were included and investigated clinically, electrophysiologically, and ultrasonographically. Fifty-four healthy asymptomatic volunteers were investigated ultrasonographically.

RESULTS
The prevalence of bifid median nerves is equal in patients with CTS and controls. Electrophysiological and ultrasonographic abnormalities are more pronounced in patients with non-bifid median nerves. Some outcome data are better in patients with non-bifid median nerves, but others do not show significant differences.

CONCLUSIONS
A bifid median nerve is not an independent risk factor for development of CTS. Some of our data suggest outcome after surgical decompression to be different, but others do not. The surgical technique in these patients may therefore have to be reevaluated.

Kasius|Kristel M|KM|
Claes|Franka|F|
Meulstee|Jan|J|
Verhagen|Wim Im|WI|

bifid median nerve
carpal tunnel syndrome
outcome
nerve conduction studies
ultrasonography


Morin Hydrate Inhibits Influenza Virus entry into Host Cells and Has Anti-inflammatory Effect in Influenza-infected Mice.

Abstract: Influenza virus is the major cause of seasonal and pandemic flu. Currently, oseltamivir, a potent and selective inhibitor of neuraminidase of influenza A and B viruses, is the drug of choice for treating patients with influenza virus infection. However, recent emergence of oseltamivir-resistant influenza viruses has limited its efficacy. Morin hydrate (3,5,7,2',4'-pentahydroxyflavone) is a flavonoid isolated from Morus alba L. It has antioxidant, anti-inflammatory, neuroprotective, and anticancer effects partly by the inhibition of the NF-кB signaling pathway. However, its effects on influenza virus have not been studied. We evaluated the antiviral activity of morin hydrate against influenza A/Puerto Rico/8/1934 (A/PR/8; H1N1) and oseltamivir-resistant A/PR/8 influenza viruses in vitro. To determine its mode of action, we carried out time course experiments, and time of addition, hemolysis inhibition, and hemagglutination assays. The effects of the co-administration of morin hydrate and oseltamivir were assessed using the murine model of A/PR/8 infection. We found that morin hydrate reduced hemagglutination by A/PR/8 in vitro. It alleviated the symptoms of A/PR/8-infection, and reduced the levels of pro-inflammatory cytokines and chemokines, such as TNF-α and CCL2, in infected mice. Co-administration of morin hydrate and oseltamivir phosphate reduced the virus titers and attenuated pulmonary inflammation. Our results suggest that morin hydrate exhibits antiviral activity by inhibiting the entry of the virus.

Morin hydrate
Oseltamivir
Antivirals
Hemagglutinin
Influenza A Virus


LncRNA SNHG1 regulates vascular endothelial cell proliferation and angiogenesis via miR-196a.

Abstract: Inflammatory cytokines are important protagonists in the formation of atherosclerotic plaques, triggering effects throughout the atherosclerotic vessels due to the destruction in proliferation, migration and angiogenesis of endothelial cells. In this study, we found SNHG1 is upregulated in TNF-α-treated HUVECs. We silenced SNHG1 and found it inhibited vascular endothelial cell proliferation and angiogenesis. In the other hand, exogenetic overexpression of SNHG1 promotes proliferation, migration and angiogenesis. Then we demonstrated that SNHG1 may interact directly with miR-196a to act as a miR-196a sponge. Further, MAPK6 were predicted to be the target of miR-196a. So we blocked miR-196a, which increased expression level of MAPK6, enhanced cell proliferation, migration and angiogenesis. These data indicated that SNHG1/miR-196a/MAPK6 axis may take a part in autophagy regulation in TNF-α-treated HUVECs. The subsequent rescue experiments come to the results ascertained the specificity of SNHG1/miR-196a/MAPK6 axis in regulating MAPK6. Overall, our findings demonstrate a novel mechanism by which SNHG1 overexpression protects the function of HUVECs, which may delay the progression of AS. SNHG1/miR-196a/MAPK6 axis may be of therapeutic significance in AS.

Zhang|Liping|L| Zhang|Qiang|Q| Lv|Lingxia|L| Jianhua|Zhu|Z| Ting|Chen|C| Wu|Yutao|Y|

D061307:Human Umbilical Vein Endothelial Cells

D048053:Mitogen-Activated Protein Kinase 6

SNHG1
Inflammatory cytokines
HUVECs
Atherosclerosis


A new slipper lobster of the genus <i>Petrarctus</i> Holthuis, 2002 (Crustacea, Decapoda, Scyllaridae) from Southwest coast of India.

Abstract: A new species of slipper lobster of the genus Petrarctus Holthuis, 2002 was discovered from southwestern India during a survey of deep sea crustaceans. The new species closely resembles P. veliger Holthuis, 2002 from the Andaman Sea and western Pacific but differs mainly in the color marking on abdominal somite I, having a relatively lower cardiac tooth but with better developed tubercles on the abdomen, as well as a differently shaped anterior part of the thoracic sternum. Molecular genetic analysis also confirms the distinct taxonomic status of the new species. To fix the identity of the type species of the genus, a neotype of P. rugosus (H. Milne Edwards, 1837) was selected from a recently collected Indian specimen with color and genetic information.

Yang|Chien-Hui|CH|
Kumar|Appukuttannair Biju|AB|
Chan|Tin-Yam|TY|

Crustacea, Petrarctus, new species, slipper lobster, India


What Determines Forest Farmers' Participation in Afforestation Programs? Empirical Evidence from a Population-Based Census Survey.

Abstract: Afforestation programs have become increasingly significant as policymakers attempt to protect the environment and reduce climate change. Although many studies have examined the participation decisions of forest farm households in afforestation programs, these studies fail to consider different types of these policies. This paper fills this knowledge gap by studying the determinants of forest farms participating in two afforestation programs on plain and sloped land in Taiwan. We construct a population-based sample of forest farms drawn from agricultural census surveys in Taiwan and estimate the multinomial logit model. We find that failing to distinguish between afforestation programs may result in misleading findings. Moreover, socio-demographic and farm production characteristics also affect participation decisions. Additional results from a simple simulation exercise show that forest farms are more likely to enroll in afforestation programs on sloped land, possibly due to lower opportunity costs.

Lee|Tzong-Haw|TH| Lee|Brian|B| Chen|Yu-Long|YL| Sun|Lih-Chyun|LC| Chang|Hung-Hao|HH|

afforestation program
Taiwan
multinomial logit model
policy simulation


Patterned cutaneous hypopigmentation phenotype characterization: A retrospective study in 106 children.

Abstract:
BACKGROUND
Cutaneous patterned hypopigmentation's phenotype is highly variable and may be associated with extracutaneous anomalies.

OBJECTIVE
We evaluated the phenotypic and clinical characteristics of patients with cutaneous patterned hypopigmentation to determine whether certain patterns were more likely to be associated with underlying anomalies.

METHODS
The charts of 106 children with cutaneous patterned hypopigmentation were reviewed retrospectively (2007-2018) at Sainte-Justine University Hospital Centre, in Montreal, Canada. Retrieved information included sex, age at diagnosis, phototype, pattern, and distribution of the cutaneous lesions and the presence of extracutaneous findings. Data were recorded on a software tool which collects and analyzes phenotypic information.

RESULTS
The predominant types of cutaneous patterned hypopigmentation were along Blaschko's lines in narrow (38.7%) and broad bands (53.8%). Mixed patterns were observed in 22.5% of children. The anterior trunk and posterior trunk were most frequently affected (69% and 56%, respectively). Extracutaneous involvement, especially neurological and developmental, was present in 28.3% of patients and was significantly associated with ≥ 4 involved body sites.

CONCLUSION
Distribution and types of cutaneous patterned hypopigmentation were not predictive of extracutaneous findings, with the exception of multiple sites involvement and possibly centrofacial location and blocklike lesions. Follow-up until school entry should help identify subtler associated extracutaneous anomalies.

hypopigmentation
genetics
hypomelanosis of Ito
mosaicism


Extracorporeal Membrane Oxygenation for Severe Pediatric Respiratory Failure.

Abstract: Extracorporeal membrane oxygenation (ECMO) was developed initially in the 1960s to support refractory respiratory failure in addition to the cardiac support inherent in a venoarterial bypass circuit. Early successes occurred predominantly in the neonatal population with subsequent randomized controlled trials and comprehensive reviews concluding therapeutic efficacy for ECMO in neonatal respiratory failure. In contrast, the evidence supporting ECMO for respiratory failure in children is less definitive. However, although pediatric randomized controlled trials have not been completed, sufficient evidence in support of ECMO as a beneficial therapy for pediatric respiratory failure exists. The acceptance of clinical utility and benefit from ECMO for pediatric ARDS and the trend toward increasing venovenous ECMO use have led to its inclusion in the Pediatric Acute Lung Injury Consensus Conference as a strongly agreed upon recommendation for severe pediatric ARDS. However, the Pediatric Acute Lung Injury Consensus Conference recommendations supporting the use of ECMO for pediatric ARDS highlight the lack of evidence-based selection criteria when determining ECMO candidacy in pediatric patients with ARDS. Ultimately, decisions to proceed with ECMO and the concomitant risk of potential life-threatening complications must consider multiple factors that balance potential risks and likelihood of benefit, pre-morbid conditions and impact on potential post-ECMO quality of life, candidacy for lung transplantation, and patient and family goals of care. This review will discuss ECMO for the support of pediatric respiratory failure, ventilator management during ECMO, considerations impacting timing of decannulation, and developing techniques.

pediatrics
respiratory failure
ECMO
pediatric ARDS


Prenatal and postnatal ultrasonographic findings of the torsioned ovarian cyst: a case report and brief literature review.

Abstract: Cystic and solid tumors of the ovary are rare during the newborn period and infancy. We present the case of a term female infant born to a mother of 28 years of age and found to have a cystic abdominal mass through prenatal sonographic evaluation in the third trimester. The complex cyst was also demonstrated by postnatal abdominal ultrasonography. Laparotomy revealed a large cystic mass with a torsed right ovary. Pathologic examination of cyst revealed hemorrhagic necrosis with ovarian torsion.

Ogul|Hayri|H| Havan|Nuri|N| Pirimoglu|Berhan|B| Guvendi|Bulent|B| Kisaoglu|Abdullah|A| Kantarci|Mecit|M|

Complex ovarian cyst
Neonatal ovarian torsion
Ovarian necrosis
Ultrasonographic diagnosis


Pomegranate reverses methotrexate-induced oxidative stress and apoptosis in hepatocytes by modulating Nrf2-NF-κB pathways.

Abstract: The clinical efficacy of the widely used chemotherapeutic drug methotrexate (MTX) is limited due to its associated hepatotoxicity. Pomegranate polyphenols are of huge health benefits and known to possess remarkable antioxidant properties capable of protecting normal cells from various stimuli-induced oxidative stress and cell death. In this study, we explored the protective role of pomegranate fruit extract (PFE) in ameliorating MTX-induced hepatic damage. Male Swiss albino mice exposed to MTX (20 mg/kg body weight) exhibited distinct markers of toxicity such as increased activities of enzymes alanine transaminase, aspartate transaminase, lactate dehydrogenase and alkaline phosphatase and also increased oxidative stress in liver evidenced by increased ROS generation and lipid peroxidation. Decrease in reduced glutathione levels, superoxide dismutase, catalase, hepatic heme oxygenase 1 and NQO-1 activities were also observed. Tracing the signal transduction pathways, it was seen that MTX exposure significantly increased nuclear translocation of NF-κB coupled with increase in phosphorylated Iκ-B and down-regulation of NF-kappaB-dependent antiapoptotic protein Bcl-2. Treatment with MTX increased the expression of the apoptotic enhancer Rho/Cdc42 as well as the phosphorylation of SAPK/JNK. A shift in the Bax/Bcl-2 ratio towards apoptosis and increase in the caspase 3 level was also evident. Administration of PFE for 7 consecutive days before and after MTX challenge suppressed MTX-induced cell death, mitigated the injurious effects of MTX and offered protection against apoptosis. PFE was shown to reduce ROS generation in hepatocytes by activating the Nrf2-ARE pathway and inhibiting NF-κB as a consequence of which the antioxidant defense mechanism in the liver was up-regulated, thereby conferring protection against MTX-induced hepatotoxicity and apoptosis.

Mukherjee|Sudeshna|S| Ghosh|Sayan|S| Choudhury|Sreetama|S| Adhikary|Arghya|A| Manna|Krishnendu|K| Dey|Sanjit|S| Sa|Gaurisankar|G| Das|Tanya|T| Chattopadhyay|Sreya|S|

Pomegranate
Oxidative stress
Apoptosis
Methotrexate
Hepatotoxicity
NF-κB
Nrf2


Risk factors of complications during noninvasive mechanical ventilation -assisted flexible bronchoscopy.

Abstract:
PURPOSE
Flexible bronchoscopy (FB) causes airway narrowing and may cause respiratory failure (RF). Noninvasive mechanical ventilation (NIV) is used to treat RF. Until recently, little was known about noninvasive mechanical ventilation assisted flexible bronchoscopy (NIV-FB) risk and complications.

MATERIALS AND METHODS
A retrospective analysis of NIV-FB performed in 20 consecutive months (July 1, 2018-February 29, 2020) was performed. Indications for: FB and NIV, as well as impact of comorbidities, blood gas results, pulmonary function test results and sedation depth, were analyzed to reveal NIV-FB risk. Out of a total of 713 FBs, NIV-FB was performed in 50 patients with multiple comorbidities, acute or chronic RF, substantial tracheal narrowing, or after previously unsuccessful FB attempt.

RESULTS
In three cases, reversible complications were observed. Additionally, due to the severity of underlining disease, two patients were transferred to the ICU where they passed away after >48h. In a single variable analysis, PaO2 69 ± 18.5 and 49 ± 9.0 [mmHg] (p < 0.05) and white blood count (WBC) 10.0 ± 4.81 and 14.4 ± 3.10 (p < 0.05) were found predictive for complications. Left heart disease indicated unfavorable NIV-FB outcome (p = 0.046).

CONCLUSIONS
NIV-FB is safe in severely ill patients, however procedure-related risk should be further defined and verified in prospective studies.

Skoczyński|Szymon|S| Ogonowski|Maciej|M| Tobiczyk|Ewelina|E| Krzyżak|Damian|D| Brożek|Grzegorz|G| Wierzbicka|Anna|A| Trzaska-Sobczak|Marzena|M| Trejnowska|Ewa|E| Studnicka|Aleksandra|A| Swinarew|Andrzej|A| Kucewicz-Czech|Ewa|E| Gierek|Danuta|D| Rychlik|Wojciech|W| Barczyk|Adam|A|

Noninvasive mechanical ventilation
Flexible bronchoscopy
Respiratory failure
Airway assessment
Complication risk


Inconsistent handers show higher psychopathy than consistent handers.

Abstract: Three hundred and forty-two university students completed the Short Dark Triad (SD3) and the Edinburgh Handedness Inventory (EHI). Inconsistent handers showed higher psychopathy scores than consistent handers, and no handedness differences were observed for narcissism or Machiavellianism. Participants were further subdivided by quartile into low, moderately low, moderately high, and high psychopathy groups (non-clinical). Absolute EHI scores were equally distributed among low and moderate groups, but were significantly lower for the high psychopathy group. These findings suggest that inconsistent handedness is only associated with the upper quartile of psychopathy scores. Also, males showed significantly higher psychopathy scores than females, and the ratio of male to female inconsistent handers decreased as psychopathy score increased. No gender × handedness interaction indicated that both female and male inconsistent handers have higher psychopathy scores than consistent handers. Although significant, the effects were small and 99.6% of participants were not in the range of a potential clinical diagnosis. The reader, therefore, is strongly cautioned against equating inconsistent handedness with psychopathy.


Effective Biophysical Modeling of Cell Free Transcription and Translation Processes.

Abstract: Transcription and translation are at the heart of metabolism and signal transduction. In this study, we developed an effective biophysical modeling approach to simulate transcription and translation processes. The model, composed of coupled ordinary differential equations, was tested by comparing simulations of two cell free synthetic circuits with experimental measurements generated in this study. First, we considered a simple circuit in which sigma factor 70 induced the expression of green fluorescent protein. This relatively simple case was then followed by a more complex negative feedback circuit in which two control genes were coupled to the expression of a third reporter gene, green fluorescent protein. Many of the model parameters were estimated from previous biophysical studies in the literature, while the remaining unknown model parameters for each circuit were estimated by minimizing the difference between model simulations and messenger RNA (mRNA) and protein measurements generated in this study. In particular, either parameter estimates from published studies were used directly, or characteristic values found in the literature were used to establish feasible ranges for the parameter estimation problem. In order to perform a detailed analysis of the influence of individual model parameters on the expression dynamics of each circuit, global sensitivity analysis was used. Taken together, the effective biophysical modeling approach captured the expression dynamics, including the transcription dynamics, for the two synthetic cell free circuits. While, we considered only two circuits here, this approach could potentially be extended to simulate other genetic circuits in both cell free and whole cell biomolecular applications as the equations governing the regulatory control functions are modular and easily modifiable. The model code, parameters, and analysis scripts are available for download under an MIT software license from the Varnerlab GitHub repository.

Adhikari|Abhinav|A|
Vilkhovoy|Michael|M|
Vadhin|Sandra|S|
Lim|Ha Eun|HE|
Varner|Jeffrey D|JD|

cell free
simulation
mathematical modeling
synthetic biological circuits
systems biology


Point-of-care testing for influenza in a university emergency department: A prospective study.

Abstract:
BACKGROUND
Seasonal influenza is a burden for emergency departments (ED). The aim of this study was to investigate whether point-of-care (POC) PCR testing can be used to reduce staff sick days and improve diagnostic and therapeutic procedures.

OBJECTIVES
The aim of this study was to investigate whether point-of-care (POC) PCR testing can be used to reduce staff sick days and improve diagnostic and therapeutic procedures.

METHODS
Using a cross-over design, the cobas® Liat® Influenza A/B POC PCR test (Liat) was compared with standard clinical practice during the 2019/2020 influenza season. All adult patients (aged ≥ 18 years) with fever (≥38°C) and respiratory symptoms were included. Primary end points were the prevalence of influenza infections in the ED and staff sick days. Secondary end points were frequency of antiviral and antibacterial therapy, time between admission and test result or treatment initiation, patient disposition, ED length of stay (LOS), and for inpatients mortality and LOS. Nurses were interviewed about handling and integration of POC testing. The occurrence of SARS-CoV-2 infections coincided with the second half of the study.

RESULTS
A total of 828 patients were enrolled in the study. All 375 patients of the intervention group were tested with Liat, and 103 patients of them (27.6%) tested positive. During the intervention period, staff sick days were reduced by 34.4% (P = .023). Significantly, more patients in the intervention group received antiviral therapy with neuraminidase inhibitors (7.2% vs 3.8%, P = .028) and tested patients received antibiotics more frequently (40.0% vs 31.6%, P = .033). Patients with POC test were transferred to external hospitals significantly more often (5.6% vs 1.3%, P = .01).

CONCLUSION
We conclude that POC testing for influenza is useful in the ED, especially if it is heavily frequented by patients with respiratory symptoms.

point-of-care testing
influenza
emergency department
polymerase chain reaction
staff protection


Pharmacokinetics and clinical outcomes of nivolumab administered every 4 weeks in patients with advanced non-small-cell lung cancer: A four-case pilot study.

Abstract: This pilot study evaluated the pharmacokinetics and clinical outcome of nivolumab, administered every 4 weeks to patients with advanced non-small-cell lung cancer. The interval of nivolumab administration was changed from 2 to 4 weeks in four patients in whom tumor growth had been controlled for more than 6 months. Pharmacokinetics and clinical outcomes of nivolumab were prospectively investigated. The estimated steady-state nivolumab mean plasma concentration (±standard deviation) of each interval in the four patients was 53.1 (±15.0) at 4 weeks and 105.2 (±29.5) μg/mL at 2 weeks. No disease progression was observed in three patients for at least 1 year after the interval change; however, one patient developed interstitial lung disease within 5.6 months after the change. In conclusion, the pharmacological effects of nivolumab continued with doses administered less frequently than the standard schedule. Nevertheless, further research on nivolumab administration intervals is necessary.

Irie|Kei|K| Okada|Akira|A| Fukushima|Shoji|S| Takase|Naoto|N| Katakami|Nobuyuki|N|

Pharmacokinetics
Non-small-cell lung cancer
Administration interval
4-Week interval nivolumab


Hereditary myopathy with early respiratory failure: occurrence in various populations.

Abstract:
OBJECTIVE
Several families with characteristic features of hereditary myopathy with early respiratory failure (HMERF) have remained without genetic cause. This international study was initiated to clarify epidemiology and the genetic underlying cause in these families, and to characterise the phenotype in our large cohort.

METHODS
DNA samples of all currently known families with HMERF without molecular genetic cause were obtained from 12 families in seven different countries. Clinical, histopathological and muscle imaging data were collected and five biopsy samples made available for further immunohistochemical studies. Genotyping, exome sequencing and Sanger sequencing were used to identify and confirm sequence variations.

RESULTS
All patients with clinical diagnosis of HMERF were genetically solved by five different titin mutations identified. One mutation has been reported while four are novel, all located exclusively in the FN3 119 domain (A150) of A-band titin. One of the new mutations showed semirecessive inheritance pattern with subclinical myopathy in the heterozygous parents. Typical clinical features were respiratory failure at mid-adulthood in an ambulant patient with very variable degree of muscle weakness. Cytoplasmic bodies were retrospectively observed in all muscle biopsy samples and these were reactive for myofibrillar proteins but not for titin.

CONCLUSIONS
We report an extensive collection of families with HMERF with five different mutations in exon 343 of TTN, which establishes this exon as the primary target for molecular diagnosis of HMERF. Our relatively large number of new families and mutations directly implies that HMERF is not extremely rare, not restricted to Northern Europe and should be considered in undetermined myogenic respiratory failure.

Palmio|Johanna|J|
Evilä|Anni|A|
Chapon|Françoise|F|
Tasca|Giorgio|G|
Xiang|Fengqing|F|
Brådvik|Björn|B|
Eymard|Bruno|B|
Echaniz-Laguna|Andoni|A|
Laporte|Jocelyn|J|
Kärppä|Mikko|M|
Mahjneh|Ibrahim|I|
Quinlivan|Rosaline|R|
Laforêt|Pascal|P|
Damian|Maxwell|M|
Berardo|Andres|A|
Taratuto|Ana Lia|AL|
Bueri|Jose Antonio|JA|
Tommiska|Johanna|J|
Raivio|Taneli|T|
Tuerk|Matthias|M|
Gölitz|Philipp|P|
Chevessier|Frederic|F|
Sewry|Caroline|C|
Norwood|Fiona|F|
Hedberg|Carola|C|
Schröder|Rolf|R|
Edström|Lars|L|
Oldfors|Anders|A|
Hackman|Peter|P|
Udd|Bjarne|B|

D020022:Genetic Predisposition to Disease


Syndecan-1-Dependent Regulation of Heparanase Affects Invasiveness, Stem Cell Properties, and Therapeutic Resistance of Caco2 Colon Cancer Cells.

Abstract: The heparan sulfate proteoglycan Syndecan-1 binds cytokines, morphogens and extracellular matrix components, regulating cancer stem cell properties and invasiveness. Syndecan-1 is modulated by the heparan sulfate-degrading enzyme heparanase, but the underlying regulatory mechanisms are only poorly understood. In colon cancer pathogenesis, complex changes occur in the expression pattern of Syndecan-1 and heparanase during progression from well-differentiated to undifferentiated tumors. Loss of Syndecan-1 and increased expression of heparanase are associated with a change in phenotypic plasticity and an increase in invasiveness, metastasis and dedifferentiation. Here we investigated the regulatory and functional interplay of Syndecan-1 and heparanase employing siRNA-mediated silencing and plasmid-based overexpression approaches in the human colon cancer cell line Caco2. Heparanase expression and activity were upregulated in Syndecan-1 depleted cells. This increase was linked to an upregulation of the transcription factor Egr1, which regulates heparanase at the promoter level. Inhibitor experiments demonstrated an impact of focal adhesion kinase, Wnt and ROCK-dependent signaling on this process. siRNA-depletion of Syndecan-1, and upregulation of heparanase increased the colon cancer stem cell phenotype based on sphere formation assays and phenotypic marker analysis (Side-population, NANOG, KLF4, NOTCH, Wnt, and TCF4 expression). Syndecan-1 depletion increased invasiveness of Caco2 cells in vitro in a heparanase-dependent manner. Finally, upregulated expression of heparanase resulted in increased resistance to radiotherapy, whereas high expression of enzymatically inactive heparanase promoted chemoresistance to paclitaxel and cisplatin. Our findings provide a new avenue to target a stemness-associated signaling axis as a therapeutic strategy to reduce metastatic spread and cancer recurrence.

Katakam|Sampath Kumar|SK|
Pelucchi|Paride|P|
Cocola|Cinzia|C|
Reinbold|Rolland|R|
Vlodavsky|Israel|I|
Greve|Burkhard|B|
Götte|Martin|M|

heparanase
colon cancer
heparan sulfate
proteoglycan
cancer stem cells
syndecan


Early Probe and Drug Discovery in Academia: A Minireview.

Abstract: Drug discovery encompasses processes ranging from target selection and validation to the selection of a development candidate. While comprehensive drug discovery work flows are implemented predominantly in the big pharma domain, early discovery focus in academia serves to identify probe molecules that can serve as tools to study targets or pathways. Despite differences in the ultimate goals of the private and academic sectors, the same basic principles define the best practices in early discovery research. A successful early discovery program is built on strong target definition and validation using a diverse set of biochemical and cell-based assays with functional relevance to the biological system being studied. The chemicals identified as hits undergo extensive scaffold optimization and are characterized for their target specificity and off-target effects in in vitro and in animal models. While the active compounds from screening campaigns pass through highly stringent chemical and Absorption, Distribution, Metabolism, and Excretion (ADME) filters for lead identification, the probe discovery involves limited medicinal chemistry optimization. The goal of probe discovery is identification of a compound with sub-µM activity and reasonable selectivity in the context of the target being studied. The compounds identified from probe discovery can also serve as starting scaffolds for lead optimization studies.

assay development
drug and probe discovery
high-throughput screening
small molecules


Seesaw double GuideLiner® catheter technique for a successful bail-out procedure from blow-out type coronary perforation.

Abstract: We encountered a case of blow-out type coronary perforation at the calcified stenosis of left anterior descending artery. First, we started immediate balloon tamponade through the initial guiding catheter (GC) with a GuideLiner® catheter. Next, we introduced a second GC with a GuideLiner® catheter and successfully deployed a covered stent. Two sets of the GC with GuideLiner® catheter facilitated us to simultaneously perform temporary hemostasis with balloon tamponade and rapid delivery of a covered stent. To alternately manipulate the GuideLiner® catheters, back and forth with seesaw-like motion enabled us to minimize the interruption of balloon tamponade.

Sugimoto|Takeshi|T| Nomura|Tetsuya|T| Miyawaki|Daisuke|D| Kato|Taku|T| Keira|Natsuya|N| Tatsumi|Tetsuya|T|

Bail-out
Coronary perforation
Dual guiding catheter
Seesaw GuideLiner® technique


Unpredictable chronic mild stress exerts anxiogenic-like effects and activates neurons in the dorsal and caudal region and in the lateral wings of the dorsal raphe nucleus.

Abstract: In previous studies, we verified that exposure to unpredictable chronic mild stress (UCMS) facilitates avoidance responses in the elevated T-maze (ETM) and increased Fos-immunoreactivity in different brain structures involved in the regulation of anxiety, including the dorsal raphe (DR). Since, it has been shown that the DR is composed of distinct subpopulations of serotonergic and non-serotonergic neurons, the present study investigated the pattern of activation of these different subnuclei of the region in response to this stress protocol. Male Wistar rats were either unstressed or exposed to the UCMS procedure for two weeks and, subsequently, analyzed for Fos-immunoreactivity (Fos-ir) in serotonergic cells of the DR. To verify if the anxiogenic effects observed in the ETM could be generalized to other anxiety models, a group of animals was also tested in the light/dark transition test after UCMS exposure. Results showed that the UCMS procedure decreased the number of transitions and increased the number of stretched attend postures in the model, an anxiogenic effect. UCMS exposure also increased Fos-ir and the number of double-labeled neurons in the mid-rostral subdivision of the dorsal part of the DR and in the mid-caudal region of the lateral wings. In the caudal region of the DR there was a significant increase in the number of Fos-ir. No significant effects were found in the other DR subnuclei. These results corroborate the idea that neurons of specific subnuclei of the DR regulate anxiety responses and are differently activated by chronic stress exposure.

Lopes|Danielle A|DA|
Lemes|Jéssica A|JA|
Melo-Thomas|Liana|L|
Schor|Herbert|H|
de Andrade|José S|JS|
Machado|Carla M|CM|
Horta-Júnior|José A C|JA|
Céspedes|Isabel C|IC|
Viana|Milena B|MB|

Unpredictable chronic mild stress
Dorsal raphe
Anxiety
Fos immunoreactivity
Serotonin


Optimal isolation and xeno-free culture conditions for limbal stem cell function.

Abstract:
PURPOSE
To preserve limbal stem cell (LSC) function in vitro with xenobiotic-free culture conditions.

METHODS
Limbal epithelial cells were isolated from 139 donors using 15 variations of three dissociation solutions. All culture conditions were compared to the baseline condition of murine 3T3-J3 feeders with xenobiotic (Xeno) keratinocyte growth medium at 20% O2. Five Xeno and Xeno-free media with increasing concentrations of calcium and epidermal growth factor (EGF) were evaluated at 5%, 14%, and 20% O2. Human MRC-5, dermal (fetal, neonatal, or adult), and limbal stromal fibroblasts were compared. Statistical analysis was performed on the number of maximum serial weekly passages, percentage of aborted colonies, colony-forming efficiency (CFE), p63α(bright) cells, and RT-PCR ratio of p63α/K12. Immunocytochemistry and RT-PCR for p63α, ABCG2, Bmi1, C/EBPδ , K12, and MUC1 were performed to evaluate phenotype.

RESULTS
Dispase/TrypLE was the isolation method that consistently showed the best yield, viability, and CFE. On 3T3-J2 feeders, Xeno-free medium with calcium 0.1 mM and EGF 10 ng/mL at 20% O2 supported more passages with equivalent percentage of aborted colonies, p63α(bright) cells, and p63α/K12 RT-PCR ratio compared to baseline Xeno-media. With this Xeno-free medium, MRC-5 feeders showed the best performance, followed by fetal, neonatal, adult HDF, and limbal fibroblasts. MRC-5 feeders supported serial passages with sustained high expression of progenitor cell markers at levels as robust as the baseline condition without significant difference between 20% and 5% O2.

CONCLUSIONS
The LSC function can be maintained in vitro under appropriate Xeno-free conditions.

Stasi|Kalliopi|K|
Goings|DaVida|D|
Huang|Jiayan|J|
Herman|Lindsay|L|
Pinto|Filipa|F|
Addis|Russell C|RC|
Klein|Dahlia|D|
Massaro-Giordano|Giacomina|G|
Gearhart|John D|JD|

xeno-free
limbal
stem
cell culture
oxygen