The Impact of Block Ambulatory Scheduling on Internal Medicine Residencies: a Systematic Review.

Abstract:
BACKGROUND
Over the past decade, nearly half of internal medicine residencies have implemented block clinic scheduling; however, the effects on residency-related outcomes are unknown. The authors systematically reviewed the impact of block versus traditional ambulatory scheduling on residency-related outcomes, including (1) resident satisfaction, (2) resident-perceived conflict between inpatient and outpatient responsibilities, (3) ambulatory training time, (4) continuity of care, (5) patient satisfaction, and (6) patient health outcomes.

METHOD
The authors reviewed the following databases: Ovid MEDLINE, Ovid MEDLINE InProcess, EBSCO CINAHL, EBSCO ERIC, and the Cochrane Library from inception through March 2017 and included studies of residency programs comparing block to traditional scheduling with at least one outcome of interest. Two authors independently extracted data on setting, participants, schedule design, and the outcomes of interest.

RESULTS
Of 8139 studies, 11 studies of fair to moderate methodologic quality were included in the final analysis. Overall, block scheduling was associated with marked improvements in resident satisfaction (n = 7 studies, effect size range - 0.3 to + 0.9), resident-perceived conflict between inpatient and outpatient responsibilities (n = 5, effect size range + 0.3 to + 2.6), and available ambulatory training time (n = 5). Larger improvements occurred in programs implementing short (1 week) ambulatory blocks. However, block scheduling may result in worse physician continuity (n = 4). Block scheduling had inconsistent effects on patient continuity (n = 4), satisfaction (n = 3), and health outcomes (n = 3).

DISCUSSION
Although block scheduling improves resident satisfaction, conflict between inpatient and outpatient responsibilities, and ambulatory training time, there may be important tradeoffs with worse care continuity.

DeWaters|Ami L|AL|
Loria|Hilda|H|
Mayo|Helen|H|
Chisty|Alia|A|
Nguyen|Oanh K|OK|

D010561:Personnel Staffing and Scheduling

block
ambulatory
scheduling
systematic review
X + Y


Delineation of temperature-humidity index (THI) as indicator of heat stress in riverine buffaloes (Bubalus bubalis) of a sub-tropical Indian region.

Abstract: The erstwhile developed temperature-humidity index (THI) has been popularly used to indicate heat stress in dairy cattle and often in buffaloes. However, scientific literature suggests differences in thermotolerance and physiological responses to heat stress between cattle and buffalo. Therefore, THI range used to indicate degree of heat stress (mild, moderate, and severe) in cattle should be recalibrated for indicating heat stress in buffaloes. The present study was carried out to delineate THI range to indicate onset and severity of heat stress in buffaloes based on physiological, biochemical, and expression profiling of heat shock response (HSR) genes in animals at different THI. The result indicated early onset of heat stress in buffaloes as compared to cattle. Physiological and biochemical parameters indicated onset of mild signs of heat stress in buffaloes at THI 68-69. Significant deviation in these parameters was again observed at THI range 73-76. At THI 77-80, the physiological and biochemical responses of animals were further intensified indicating extreme alteration in homeostasis. The in vivo expression profiling of HSR genes indicated that members of Hsp70 gene family are expressed in a temporal pattern over different THIs, whereas expressions of Hsf genes were evident during intense heat stress. Overall, the study established that amplitude of heat shock response and THI range for indicating severity of thermal stress for buffaloes are not in unison to cattle. The study also suggests skin temperature of the poll region could be used as non-invasive tool for monitoring heat stress in dairy buffaloes.

Umar|Sofi Imran Ul|SIU|
Konwar|Dipanjali|D|
Khan|Asma|A|
Bhat|Mohammad Altaf|MA|
Javid|Faizan|F|
Jeelani|Rakhshan|R|
Nabi|Burhan|B|
Najar|Afaq Amin|AA|
Kumar|Dhirendra|D|
Brahma|Biswajit|B|0000-0003-0052-5029

THI
Heat stress
Buffalo
Hsp70
Hsf
Infrared thermography


Effect of Intraoperative Goal-Directed Fluid Management on Tissue Oxygen Tension in Obese Patients: a Randomized Controlled Trial.

Abstract:
BACKGROUND
Perioperative subcutaneous tissue oxygen tension (PsqO2) is substantially reduced in obese surgical patients. Goal-directed fluid therapy optimizes cardiac performance and thus tissue perfusion and oxygen delivery. We therefore tested the hypothesis that intra- and postoperative PsqO2 is significantly reduced in obese patients undergoing standard fluid management compared to goal-directed fluid administration.

METHODS
We randomly assigned 60 obese patients (BMI ≥ 30 kg/m2) undergoing laparoscopic bariatric surgery to receive either esophageal Doppler-guided goal-directed fluid management or conventional fluid treatment. Our primary outcome parameter was intra- and postoperative PsqO2 measured with a polarographic electrode in the subcutaneous tissue of the upper arm. A random effects linear regression model was used to analyze the effect of intervention.

RESULTS
Overall, mean (± SD) PsqO2 was significantly higher in obese patients receiving goal-directed therapy compared to conventional fluid therapy (65.8 ± 28.0 mmHg vs. 53.7 ± 21.7, respectively; repeated measures design adjusted difference: 13.0 mmHg [95% CI 2.3 to 23.7; p = 0.017]). No effect was seen intraoperatively (69.6 ± 27.9 mmHg vs. 61.4 ± 28.8, difference: 9.7 mmHg [95% CI -3.8 to 23.2; p = 0.160]); however, goal-directed fluid management improved PsqO2 in the early postoperative phase (63.1 ± 27.9 mmHg vs. 48.4 ± 12.5, difference: 14.5 mmHg [95% CI 4.1 to 24.9; p = 0.006]). Intraoperative fluid requirements did not differ between the two groups.

CONCLUSIONS
Goal-directed fluid therapy improved subcutaneous tissue oxygenation in obese patients. This effect was more pronounced in the early postoperative period.

CLINICAL TRIAL NUMBER AND REGISTRY
The study was registered at ClinicalTrials.gov (NCT01052519).

Tissue oxygen tension
Obesity
Goal-directed fluid therapy
Laparoscopic surgery


Genetic characterization of the honeybee ectoparasitic mite Varroa destructor from Benin (West Africa) using mitochondrial and microsatellite markers.

Abstract: Varroa destructor is one of the scourges of global beekeeping. It was detected for the first time in Benin in 2011 on the honeybee Apis mellifera adansonii. The aim of this study was to identify the strain of Varroa sp. found and study its genetic diversity. In total 183 Varroa mites were sampled in 21 municipalities in Benin. The COI intergenic region of each mite mtDNA was amplified by PCR. The SacI restriction enzyme was used to determine the strains of Varroa sp. Only the Korean (K) haplotype, identical to the most prevalent strain in Africa, was detected. Analysis of the genetic diversity of Varroa mites with eight microsatellite loci (Simple Sequence Repeats) indicated a very low diversity of genotypes. Thus, V. destructor populations from Benin appear to make up a single group. Their clonal wealth ranges from 0.00 to 0.47. This study is an important step forward in the monitoring of the infestation of V. destructor.

Kelomey|Aude E|AE|
Paraiso|Armand|A|
Sina|Haziz|H|
Legout|Hélène|H|
Garnery|Lionel|L|
Baba-Moussa|Lamine|L|

Varroa destructor
Benin
Microsatellite markers
Apis mellifera
Clonal species
Mitochondrial DNA


New phenolic glycosides from Polygonum cuspidatum.

Abstract: Two new isobenzofuranone derivatives, polyphthaliside A (1) and polyphthaliside B (2), and a new isocoumarin derivative, polyisocoumarin (3), were isolated from Polygonum cuspidatum. Their structures were elucidated by detailed spectroscopic analysis and chemical methods. The cytotoxicity activity and PTP1B inhibitory activity of compounds 1-3 were estimated and none of them exhibited activities at a concentration of 10 μM.

Jiang|Jian-Shuang|JS| Li|Fu-Shuang|FS| Feng|Zi-Ming|ZM| Yang|Ya-Nan|YN| Zhang|Pei-Cheng|PC|

Polygonum cuspidatum
isobenzofuranone
isocoumarin
cytotoxicity activity
PTP1B


Impact of whole egg intake on blood pressure, lipids and lipoproteins in middle-aged and older population: A systematic review and meta-analysis of randomized controlled trials.

Abstract:
BACKGROUND AND AIM
Effects of whole egg consumption on cardiovascular diseases (CVD) risk in the middle-aged and older population remain unclear due to inconsistent findings from observational and randomized controlled trials (RCTs). This meta-analysis aimed to assess the impacts of whole egg and egg category (whole eggs versus egg substitutes) intake quantity on CVD risk factors from systematically searched RCTs. Egg substitutes were hypothesized to have minimal effects of the blood lipid and lipoprotein profile as they are void of dietary cholesterol.

METHODS AND RESULTS
As many as 434 studies identified from PubMed, Cochrane Library, CINAHL and Medline (Ovid) databases were screened and data were extracted from 8 selected RCTs. Quality of the selected studies were assessed and the overall effect sizes of weighted mean differences (WMD) were calculated using a random effects model. Non-differential effects in blood pressures, lipids and lipoproteins were observed when >4 whole eggs/week compared to ≤4 whole eggs/week were consumed. Intake of >4 whole eggs/week compared to equivalent amounts of egg substitutes caused greater elevations in blood total cholesterol (WMD: 0.198 mmol/L; 95% CIs: 0.056, 0.339), HDL cholesterol (WMD: 0.068 mmol/L; 95% CIs: 0.006, 0.130) and LDL cholesterol (WMD: 0.171 mmol/L; 95% CIs: 0.028, 0.315) but did not differentially affect triglycerides concentration.

CONCLUSION
Overall, the results support the notion that quantity of whole egg intake does not affect CVD risk factors and consuming egg substitutes may also be beneficial compared to whole eggs on lowering CVD risk in the middle-aged and older population.

D016032:Randomized Controlled Trials as Topic

Whole eggs
Blood pressure
Cardiovascular disease
Egg category
Blood lipids and lipoproteins
Dietary cholesterol
Middle-aged and older adults


Multicenter study of environmental contamination with cyclophosphamide, ifosfamide, and methotrexate in 48 Canadian hospitals.

Abstract: Context Oncology workers are occupationally exposed to antineoplastic drugs. This exposure can induce adverse health effects. In order to reduce their exposure, contamination on surfaces should be kept as low as possible. Objectives To monitor environmental contamination with cyclophosphamide, ifosfamide, and methotrexate in oncology pharmacy and patient care areas in Canadian hospitals. To describe the impact of some factors that may limit contamination. Methods This is a descriptive study. Twelve standardized sites were sampled in each participating center (six in the pharmacy and six in patient care areas). Samples were analyzed for the presence of cyclophosphamide, ifosfamide, and methotrexate by ultra-performance liquid chromatography tandem mass spectrometry technology. Descriptive statistical analyses were done and results were compared with a Kolmogorov-Smirnov test for independent samples. Results In 2015, 48 hospitals participated in this study (48/202, 24%). Overall, 34% (181/525) of the samples were positive for cyclophosphamide, 8% (41/525) for ifosfamide, and 6% (31/525) for methotrexate. The 75th percentile value of cyclophosphamide surface concentration was 6.9 pg/cm2. For ifosfamide and methotrexate, they were lower than the limit of detection. Centers who prepared more antineoplastic drugs per year and centers who used more cyclophosphamide per year showed significantly higher surface contamination ( p < 0.0001). Over the years, we observed a reduction in surface contamination. Conclusion In comparison with other multicenter studies that were conducted in Canada, the concentration of antineoplastic drugs measured on surfaces is decreasing. Regular environmental monitoring is a good practice in order to maintain contamination as low as reasonably achievable.

Poupeau|Céline|C|
Tanguay|Cynthia|C|
Caron|Nicolas J|NJ|
Bussières|Jean-François|JF|

cyclophosphamide
Antineoplastic drugs
environmental monitoring
occupational exposure


Changes in structure and function of bacterial and fungal communities in open composting of Chinese herb residues.

Abstract: In this study, dynamic changes in bacterial and fungal communities, metabolic characteristics, and trophic modes in Chinese herb residues open composting for 30 days were analyzed by using high-throughput sequencing, PICRUSt, and FUNGuild, respectively. Bacillaceae and Basidiomycota predominated at the early composting stage, while Proteobacteria and Ascomycota became the dominant phyla during the active phase. Aerobic composting had a significant effect on bacterial metabolic characteristics and fungal trophic modes over the composting time. The function of the bacterial communities changed from environmental information processing to metabolism. Fungal communities changed as well, with the pathogenic fungi decreasing and wood saprotrophs increasing. These results indicated that open composting of Chinese herb residues not only influenced microbial community structure but also changed metabolic characteristics and trophic modes, which became the internal dynamics of composting.

Chang|Fan|F| Jia|Fengan|F| Lv|Rui|R| Zhen|Lisha|L| Li|Yan|Y| Wang|Yan|Y|

résidus de plantes médicinales chinoises


First steps in life cycle assessments of cities with a sustainability perspective: A proposal for goal, function, functional unit, and reference flow.

Abstract: This study highlights the need and suggests some basis for working on the Life Cycle Assessment (LCA) of cities with a sustainability perspective. Cities are relevant actors in sustainable development and contribute to the generation of significant environmental impacts upstream and downstream their internal activity. LCA is precise in assessing environmental aspects of sustainability but lacks social and economic inputs. It is important to avoid problem shifting, even between the different dimensions of sustainability. A systematic literature review has been performed so as to extract the procedure for defining the goal, function, functional unit, and reference flow of a complex system. The existing literature is mainly product focused, although services are also considered somehow. The procedure for defining the abovementioned items is previously applied to a relatively simple system, a power generation plant, so as to find parallelisms to define those items for a complex system such as a city. To obtain a feasible (i.e., simplified) city Life Cycle Sustainability Assessment, the authors propose to introduce the social and economic aspects through the use of the City Prosperity Index (CPI) as technical performance within the FU of the city LCA. The CPI combined with the number of inhabitants is the normalization factor which is found to be more suitable to avoid problem shifting among sustainability dimensions and to avoid the interference of the number of inhabitants when comparing two different cities. An exemplification of the variation of the results after the application of these two factors in 18 cities' CO2-eq emissions is described. Even though this is not a large sample, it includes cities from different continents and levels of development and, thus it can be useful to see the how the suggested method is affecting cities' ranking.

D003247:Conservation of Natural Resources

Environmental impacts
City assessment
City definition
Holistic approach
Systemic approach
Urban regions


Detection of allele frequencies of common c. 511C>T and c.625G>A variants in the ACADS gene in the Turkish population.

Abstract: Short-chain acyl-CoA dehydrogenase deficiency (SCADD) is a rare inborn error of mitochondrial fatty acid oxidation and protein misfolding disorder. Our aim was to detect the number of Turkish patients diagnosed with SCADD in the literature and to determine the allele frequencies of two common variants (c.511C > T and c.625G > A) in the Turkish population. Five Turkish patients with SCADD were reported in the literature from four unrelated families. We also investigated allele frequencies of common variants of c.511C > T and c.625G > A, which confer susceptibility to SCADD, which were found to be 1.7% and 20.2%, respectively. Both of these susceptibility variants were found to be high in the Turkish population as they are worldwide.

Kılıç|Mustafa|M|
Ergüner|Bekir|B|
Koşukçu|Can|C|
Özgül|Rıza Köksal|RK|

D042964:Acyl-CoA Dehydrogenase
D005787:Gene Frequency
D006801:Humans
D008052:Lipid Metabolism, Inborn Errors

short-chain acyl-CoA dehydrogenase deficiency


Suspected paracetamol overdose in Monrovia, Liberia: a matched case-control study.

Abstract:
BACKGROUND
A cluster of cases of unexplained multi-organ failure was reported in children at Bardnesville Junction Hospital (BJH), Monrovia, Liberia. Prior to admission, children's caregivers reported antibiotic, antimalarial, paracetamol, and traditional treatment consumption. Since we could not exclude a toxic aetiology, and paracetamol overdose in particular, we implemented prospective syndromic surveillance to better define the clinical characteristics of these children. To investigate risk factors, we performed a case-control study.

METHODS
The investigation was conducted in BJH between July 2015 and January 2016. In-hospital syndromic surveillance identified children with at least two of the following symptoms: respiratory distress with normal pulse oximetry while breathing ambient air; altered consciousness; hypoglycaemia; jaundice; and hepatomegaly. After refining the case definition to better reflect potential risk factors for hepatic dysfunction, we selected cases identified from syndromic surveillance for a matched case-control study. Cases were matched with in-hospital and community-based controls by age, sex, month of illness/admission, severity (in-hospital), and proximity of residence (community).

RESULTS
Between July and December 2015, 77 case-patients were captured by syndromic surveillance; 68 (88%) were under three years old and 35 (46%) died during hospitalisation. Of these 77, 30 children met our case definition and were matched with 53 hospital and 48 community controls. Paracetamol was the most frequently reported medication taken by the cases and both control groups. The odds of caregivers reporting supra-therapeutic paracetamol consumption prior to admission was higher in cases compared to controls (OR 6.6, 95% CI 2.1-21.3). Plasma paracetamol concentration on day of admission was available for 19 cases and exceeded 10 μg/mL in 10/13 samples collected on day one of admission, and 4/9 (44%) collected on day two.

CONCLUSIONS
In a context with limited diagnostic capacity, this study highlights the possibility of supratherapeutic doses of paracetamol as a factor in multi-organ failure in a cohort of children admitted to BJH. In this setting, a careful history of pre-admission paracetamol consumption may alert clinicians to the possibility of overdose, even when confirmatory laboratory analysis is unavailable. Further studies may help define additional toxicological characteristics in such contexts to improve diagnoses.

Haidar|Mohamad K|MK|0000-0002-7260-5493
Vogt|Florian|F|
Takahashi|Kensuke|K|
Henaff|Fanny|F|
Umphrey|Lisa|L|
Morton|Nikola|N|
Bawo|Luke|L|
Kerkula|Joseph|J|
Ferner|Robin|R|
Porten|Klaudia|K|
Baud|Frederic J|FJ|

Paracetamol
Liberia
Liver insufficiency
Paediatrics


Intensity-dependent gene expression after aerobic exercise in endurance-trained skeletal muscle.

Abstract: We investigated acute exercise-induced gene expression in skeletal muscle adapted to aerobic training. Vastus lateralis muscle samples were taken in ten endurance-trained males prior to, and just after, 4 h, and 8 h after acute cycling sessions with different intensities, 70% and 50%   . High-throughput RNA sequencing was applied in samples from two subjects to evaluate differentially expressed genes after intensive exercise (70%   ), and then the changes in expression for selected genes were validated by quantitative PCR (qPCR). To define exercise-induced genes, we compared gene expression after acute exercise with different intensities, 70% and 50%   , by qPCR. The transcriptome is dynamically changed during the first hours of recovery after intensive exercise (70%   ). A computational approach revealed that the changes might be related to up- and down-regulation of the activity of transcription activators and repressors, respectively. The exercise increased expression of many genes encoding protein kinases, while genes encoding transcriptional regulators were both up- and down-regulated. Evaluation of the gene expression after exercise with different intensities revealed that some genes changed expression in an intensity-dependent manner, but others did not: the majority of genes encoding protein kinases, oxidative phosphorylation and activator protein (AP)-1-related genes significantly correlated with markers of exercise stress (power, blood lactate during exercise and post-exercise blood cortisol), while transcriptional repressors and circadian-related genes did not. Some of the changes in gene expression after exercise seemingly may be modulated by circadian rhythm.

Popov|Daniil V|DV|
Makhnovskii|Pavel A|PA|
Kurochkina|Nadia S|NS|
Lysenko|Evgeny A|EA|
Vepkhvadze|Tatiana F|TF|
Vinogradova|Olga L|OL|

Gene expression
Skeletal muscle
Transcriptome
Circadian rhythm
Endurance exercise


A self-regulating biomolecular comparator for processing oscillatory signals.

Abstract: While many cellular processes are driven by biomolecular oscillators, precise control of a downstream on/off process by a biochemical oscillator signal can be difficult: over an oscillator's period, its output signal varies continuously between its amplitude limits and spends a significant fraction of the time at intermediate values between these limits. Further, the oscillator's output is often noisy, with particularly large variations in the amplitude. In electronic systems, an oscillating signal is generally processed by a downstream device such as a comparator that converts a potentially noisy oscillatory input into a square wave output that is predominantly in one of two well-defined on and off states. The comparator's output then controls downstream processes. We describe a method for constructing a synthetic biochemical device that likewise produces a square-wave-type biomolecular output for a variety of oscillatory inputs. The method relies on a separation of time scales between the slow rate of production of an oscillatory signal molecule and the fast rates of intermolecular binding and conformational changes. We show how to control the characteristics of the output by varying the concentrations of the species and the reaction rates. We then use this control to show how our approach could be applied to process different in vitro and in vivo biomolecular oscillators, including the p53-Mdm2 transcriptional oscillator and two types of in vitro transcriptional oscillators. These results demonstrate how modular biomolecular circuits could, in principle, be combined to build complex dynamical systems. The simplicity of our approach also suggests that natural molecular circuits may process some biomolecular oscillator outputs before they are applied downstream.

Agrawal|Deepak K|DK|
Franco|Elisa|E|
Schulman|Rebecca|R|

biomolecular comparator
oscillator
modular
dynamical systems
synthetic biology


Salvianolic acid B induced upregulation of miR-30a protects cardiac myocytes from ischemia/reperfusion injury.

Abstract:
BACKGROUND
MicroRNAs (miRNAs) are a novel class of powerful, endogenous regulators of gene expression. This study was designed to ascertain if miR-30a is involved in the cardioprotective actions of salvianolic acid B (Sal B) against myocardial ischemia-reperfusion (I-R) injury through suppression of autophagy.

METHODS
Murine myocardial cells that had undergone primary culture were induced by I-R and incubated with Sal B (25, 50, 100 μM) in the presence of a miR-30a mimic or miR-30a inhibitor. Expression of miR-30a, beclin-1, LC3-II and p-Akt protein, cell viability, and lactic acid dehydrogenase (LDH) release were assessed.

RESULTS
miR-30a expression was down-regulated remarkably in I-R cells, and this suppression could be reversed by Sal B in a dose-dependent manner. Sal B repressed autophagy in I-R myocardial cells. Sal B improved cell viability and reduced the rate of LDH leakage, which suggested that autophagy suppression was beneficial for cell survival. Knockdown of miR-30a with a miR-30a inhibitor could reverse the anti-autophagy effect of Sal B against I-R injury. Furthermore, we confirmed that Sal B has a protective role in miR-30a-mediated autophagy through the PI3K/Akt signaling pathway, which was abrogated by the PI3K inhibitor LY294002.

CONCLUSIONS
These data suggest that miR-30a is involved in Sal B-mediated cardioprotection against I-R injury through the PI3K/Akt signaling pathway.

Li|Dan|D| Wang|Jun|J| Hou|Jincai|J| Fu|Jianhua|J| Liu|Jianxun|J| Lin|Ruichao|R|

Salvianolic acid B
miR-30a
Autophagy
Ischemic heart disease


Treatment of COVID-19 in pregnant women: A systematic review and meta-analysis.

Abstract:
OBJECTIVE
Clinical trials evaluating pharmacological and non-pharmacological treatment of COVID-19, either excluded pregnant women or included very few women. Unlike the numerous systematic reviews on prevalence, symptoms and adverse outcomes of COVID-19 in pregnancy, there are very few on the effects of treatment on maternal and neonatal outcomes in pregnancy. We undertook a systematic review of all published and unpublished studies on the effects of pharmacological and non-pharmacological interventions for COVID-19 on maternal and neonatal pregnancy outcomes.

DATA SOURCES
We performed a systematic literature search of the following databases: Medline, Embase, Cochrane database, WHO (World Health Organization) COVID-19 database, China National Knowledge Infrastructure (CNKI), and Wanfang databases from 1 December 2019 to 1 December 2020.

STUDY ELIGIBILITY CRITERIA
Studies were only included if they involved pregnant or postnatal women who were exposed to pregnancy specific interventions like the mode of delivery and type of anaesthesia, pharmacological or non-pharmacological interventions.

STUDY APPRAISAL AND SYNTHESIS METHODS
We first screened the titles and abstracts of studies and then assessed the full text of the selected studies in detail for eligibility. Data on study design, population, type of screening for COVID-19, country, hospital, country status (high or low and middle income), treatment given (mode of delivery, type of anaesthesia, type of pharmacological and non-pharmacological treatment was extracted. The pre-defined maternal outcomes we collected were mode of delivery (vaginal or by caesarean section), severe or critical COVID-19 (as defined by the authors), symptomatic COVID-19, maternal death, maternal hospital admission, ICU admission, mechanical ventilation, ECMO and maternal pneumonia. The pre-defined neonatal outcomes we extracted were preterm birth (<37 weeks), stillbirth, neonatal death, NICU admission, neonatal COVID-19 positive, neonatal acidosis (pH < 7.0) and Apgar scores (<8 after 5 min). Study quality assessment was performed.

RESULTS
From a total of 342 potential eligible studies, we included 27 studies in our systematic review, including 4943 pregnant women (appendix 3). Sixteen studies had a retrospective cohort design and 11 a prospective cohort design. There were no randomised controlled trials. There was a significant association between caesarean section and admission to ICU (OR 4.99, 95% CI 1.24 to 20.12; 4 studies, 153 women, I2 = 0%), and diagnosis of maternal COVID-19 pneumonia as defined by study authors (OR 3.09, 95% CI 1.52 to 6.28; 2 studies, 228 women, I2 = 0%). Women who had a preterm birth were more likely to have the baby via caesarean section (OR 3.03, 95% CI 1.71 to 5.36, 12 studies; 314 women, I2 = 0%). For pharmacological and non-pharmacological we provided estimates of the expected rates of outcomes in women exposed to various treatment of COVID-19. Comparative data for pregnant women, in particular for treatments proven to be effective in the general population, however, is lacking to provide clinically meaningful interpretation.

CONCLUSIONS
We found associations for pregnancy specific interventions, like mode of delivery and outcomes of the disease, but there were too few data on pharmacological and non-pharmacological treatments in pregnant women with COVID-19. We report the rates of complications found in the literature. We encourage researchers to include pregnant women in their trials and report the data on pregnant women separately.

Giesbers|Steven|S| Goh|Edwina|E| Kew|Tania|T| Allotey|John|J| Brizuela|Vanessa|V| Kara|Edna|E| Kunst|Heinke|H| Bonet|Mercedes|M| Thangaratinam|Shakila|S| |||

Treatment
COVID-19
Systematic review
Meta-analysis
Pregnancy
Neonatal


Preparation and properties of cellulose/Thespesia lampas microfiber composite films.

Abstract: The fibers from the newly identified plant Thespesia lampas (TL) were converted into microfibers in order to increase their aspect ratio. The TL microfibers (TLMFs) were used as reinforcement (1 wt. to 5 wt%) in cellulose matrix to prepare cellulose /TLMFs composite films. These composite films were characterized by polarized optical microscopy (POM), scanning electron microscopy (SEM), Fourier transform infrared (FTIR) spectroscopy, X-ray diffraction (XRD), thermogravimetric analysis (TGA) and tensile tests. The POM and SEM images indicated the uniform distribution of TLMFs but in random orientation in the composites. FTIR spectral analysis indicated the presence of minor quantity of lignin in the microfibers in spite of chemical treatment of fibers. The XRD analysis indicated higher crystallinity index for the composites than the matrix. Thermal stability of the composite films was slightly higher than the matrix. Tensile modulus and tensile strength were lower while the elongation at break of the composite films was higher than those of the cellulose matrix due to random orientation of the TLMFs in the composites. However the tensile properties and thermal stability of the cellulose/TLMFs composites were found to be higher than those of the cellulose/alkali treated TL fiber composites and hence can be considered for packaging applications.

B|Ashok|A|
K|Obi Reddy|OR|
Feng|HuaTian|H|
A|Varada Rajulu|VR|

Thespesia lampas
Composites
Thermal stability
Tensile properties
Micro fibers


Hypersexuality: A Critical Review and Introduction to the "Sexhavior Cycle".

Abstract: An empirical review of hypersexuality is timely as "compulsive sexual behavior" is being considered as an impulse control disorder for inclusion in the forthcoming International Classification of Diseases, 11th ed. Specifically, hypersexuality has been conceptualized in the literature as the inability to regulate one's sexual behavior that is a source of significant personal distress. Various theoretical models have been posited in an attempt to understand the occurrence of hypersexuality, although disagreement about these divergent conceptualizations of the condition has made assessment and treatment of hypersexual clients more challenging. Theories of sexual compulsivity, sexual impulsivity, dual control (sexual inhibition/excitation), and sex addiction are critically examined, as are the diagnostic criteria for clinically assessing hypersexuality as a sexual disorder. Our discussion of hypersexuality covers a diversity of research and clinical perspectives. We also address various challenges associated with reliably defining, psychometrically measuring, and diagnosing hypersexuality. Furthermore, literature is reviewed that expresses concerns regarding whether hypersexuality (conceptualized as a disorder) exists, whether it is simply normophilic behavior at the extreme end of sexual functioning, or alternatively is a presenting problem that requires treatment rather than a clinical diagnosis. Following our literature review, we developed the "sexhavior cycle of hypersexuality" to potentially explain the neuropsychology and maintenance cycle of hypersexuality. The sexhavior cycle suggests that, for some hypersexual persons, high sexual arousal may temporarily and adversely impact cognitive processing (cognitive abeyance) and explain a repeated pattern of psychological distress when interpreting one's sexual behavior (sexual incongruence). We also suggest that further research is required to validate whether hypersexuality is a behavioral disorder (such as gambling), although some presentations of the condition appear to be symptomatic of a heterogeneous psychological problem that requires treatment.

Hypersexuality
Sexhavior cycle
Sexual compulsivity
Sexual impulsivity
Sex addiction
DSM-5
Dual control model
ICD-11


Sex Differences in Intestinal Carbohydrate Metabolism Promote Food Intake and Sperm Maturation.

Abstract: Physiology and metabolism are often sexually dimorphic, but the underlying mechanisms remain incompletely understood. Here, we use the intestine of Drosophila melanogaster to investigate how gut-derived signals contribute to sex differences in whole-body physiology. We find that carbohydrate handling is male-biased in a specific portion of the intestine. In contrast to known sexual dimorphisms in invertebrates, the sex differences in intestinal carbohydrate metabolism are extrinsically controlled by the adjacent male gonad, which activates JAK-STAT signaling in enterocytes within this intestinal portion. Sex reversal experiments establish roles for this male-biased intestinal metabolic state in controlling food intake and sperm production through gut-derived citrate. Our work uncovers a male gonad-gut axis coupling diet and sperm production, revealing that metabolic communication across organs is physiologically important. The instructive role of citrate in inter-organ communication might be significant in more biological contexts than previously recognized.

Hudry|Bruno|B|
de Goeij|Eva|E|
Mineo|Alessandro|A|
Gaspar|Pedro|P|
Hadjieconomou|Dafni|D|
Studd|Chris|C|
Mokochinski|Joao B|JB|
Kramer|Holger B|HB|
Plaçais|Pierre-Yves|PY|
Preat|Thomas|T|
Miguel-Aliaga|Irene|I|

intestine
carbohydrate metabolism
sperm
sexual dimorphisms
Drosophila
gonad
citrate
gender differences
organ plasticity
testes


Incremental value of live/real time three-dimensional transthoracic echocardiography over the two-dimensional technique in assessing carcinoid heart disease involving the aortic valve.

Abstract: We present a case of an adult with metastatic carcinoid heart disease, in whom live/real time three-dimensional transthoracic echocardiography provided incremental value over two-dimensional transthoracic echocardiography in assessing involvement of the aortic valve.

Bulur|Serkan|S|
Hsiung|Ming C|MC|
Nanda|Navin C|NC|
Hardas|Shalaka|S|
Mohamed|Ahmed|A|
ElKaryoni|Ahmed|A|
Srialluri|Swetha|S|
Barssoum|Kirolos|K|
Elsayed|Mahmoud|M|
Wei|Jeng|J|
Yin|Wei-Hsian|WH|


Short Chain Fatty Acid Acetate Protects against Ethanol-Induced Acute Gastric Mucosal Lesion in Mice.

Abstract: Short chain fatty acids acetate and propionate have been demonstrated protective function in the intestinal mucosa. However, their impact on gastric mucosa has not yet been elucidated. The current study aimed to investigate the potential protective effects of acetate and propionate against ethanol-induced gastric mucosal lesion and the underlying mechanism in mice. ICR mice were orally treated with acetate and propionate, respectively, 30 min prior to the establishment of gastric mucosal injury model by challenge with absolute ethanol. The gastric samples were collected for the detection of oxidative, inflammatory and apoptotic related parameters. Acetate, but not propionate, attenuated the severity of gastric mucosal damage as evidenced by the gross changes of gastric mucosa, pathological aberrations. Acetate alleviated oxidative stress as shown by the increase in glutathione (GSH) content and superoxide dismutase (SOD) activities, and the decrease of malondialdehyde (MDA) level. The elevated concentrations of interleukin (IL)-1β, tumor necrosis factor (TNF)-α and IL-6, and the activation of nuclear factor-kappaB (NF-κB) p65 by ethanol stimulation was also reduced by acetate. Moreover, the anti-inflammatory factors, IL-4, LXA4 and IL-10, were up-regulated in acetate treated group. With respect to gastric mucosal apoptosis, acetate suppressed caspase-3 activity and BAX expression in favor of cell survival. These favorable actions were maybe associated with up-regulation of the gastric MUC5AC, the key defense factor of gastric mucosal system. These findings accentuate the gastroprotective actions of acetate in ethanol-induced gastric injury which were mediated via concerted multi-prolonged actions, including suppression of gastric oxidation, inflammation and apoptosis and promotion of MUC5AC expression.

Liu|Jiaming|J| Wang|Jindan|J| Shi|Yilu|Y| Su|Wei|W| Chen|Jie|J| Zhang|Zhengzheng|Z| Wang|Guocan|G| Wang|Fangyan|F|

D002492:Central Nervous System Depressants

short chain fatty acid
acetate
gastric mucosa
ethanol
oxidative stress
inflammation


Race disparities in cardiovascular disease risk factors within socioeconomic status strata.

Abstract:
PURPOSE
Racial differences in socioeconomic status (SES) explain some, but not all, of racial disparities in cardiovascular disease (CVD) risk. To address this, race disparities among higher SES individuals need to be assessed. The purpose of this study was to assess whether racial disparities in CVD risk factors differ by SES levels.

METHODS
Data from the National Health and Nutritional Examination Survey 2007-2014 were used to calculate racial differences in hypertension, high cholesterol, diabetes, and obesity. Interactions between race and SES were assessed.

RESULTS
African Americans had higher odds of hypertension (odds ratio [OR], 1.90; 95% confidence interval [CI], 1.72-2.09), diabetes (OR, 1.66; 95% CI, 1.33-2.07), and obesity (OR, 1.64; 95% CI, 1.46-1.83) than whites. Significant interactions between race and income greater than or equal to $100,000 were observed for obesity (OR, 1.55; 95% CI, 1.24-1.94) and between race and education (college graduate or more; OR, 1.58; 95% CI, 1.16-2.15). Disparities in diabetes were observed in the highest SES groups, but not among those in the lowest SES groups.

CONCLUSIONS
Race disparities in some CVD risk factors varied by SES levels. Results suggest that race disparities in obesity are larger among those with income greater than or equal to $100,000 and who are college graduates. It is possible that African Americans experience fewer health-related benefits of increased income and education levels compared with whites.

Bell|Caryn N|CN|
Thorpe|Roland J|RJ|
Bowie|Janice V|JV|
LaVeist|Thomas A|TA|

Hypertension
Obesity
African Americans
Diabetes mellitus
Social class


Synthesis and biological activity of novel tert-amylphenoxyalkyl (homo)piperidine derivatives as histamine H3R ligands.

Abstract: As a continuation of our search for novel histamine H3 receptor ligands a series of twenty new tert-amyl phenoxyalkylamine derivatives (2-21) was synthesized. Compounds of four to eight carbon atoms spacer alkyl chain were evaluated on their binding properties at human histamine H3 receptor (hH3R). The highest affinities were observed for pentyl derivatives 6-8 (Ki=8.8-23.4nM range) and among them piperidine derivative 6 with Ki=8.8nM. Structures 6, 7 were also classified as antagonists in cAMP accumulation assay (with EC50=157 and 164nM, respectively). Moreover, new compounds were also evaluated for anticonvulsant activity in Antiepileptic Screening Program (ASP) at National Institute of Neurological Disorders and Stroke (USA). Seven compounds (2-4, 9, 11, 12 and 20) showed anticonvulsant activity at maximal electroshock (MES) test in the dose of 30mg/kg at 0.5h. In the subcutaneous pentetrazole (scMET) test compound 4 showed protection at 100 and 300mg/kg dose at mice, however compounds showed high neurotoxicity in rotarod test at used doses. Also, molecular modeling studies were undertaken, to explain affinity of compounds at hH3R (taking into the consideration X-ray analysis of compound 18). In order to estimate "drug-likeness" of selected compounds in silico and experimental evaluation of lipophilicity, metabolic stability and cytotoxicity was performed.

Kuder|Kamil J|KJ|
Łażewska|Dorota|D|
Kaleta|Maria|M|
Latacz|Gniewomir|G|
Kottke|Tim|T|
Olejarz|Agnieszka|A|
Karcz|Tadeusz|T|
Fruziński|Andrzej|A|
Szczepańska|Katarzyna|K|
Karolak-Wojciechowska|Janina|J|
Stark|Holger|H|
Kieć-Kononowicz|Katarzyna|K|

Piperidine derivatives
Anticonvulsants
Drug-like properties
Histamine H(3) receptor
Histamine H(3) receptor ligands
Molecular docking
Non-imidazole histamine H(3)R ligands


Inhibition of human neutrophil activity by an RNA aptamer bound to interleukin-8.

Abstract: Interleukin-8 (IL-8) is a proinflammatory CXC chemokine that has been associated with the promotion of neutrophil chemotaxis, degranulation, and the pathogenesis of several neutrophil-infiltrating chronic inflammatory diseases. In the current study, we generated and characterized a 2'-fluoro-pyrimidine modified RNA aptamer (8A-35) against human IL-8. The 8A-35 aptamer binds to IL-8 with high specificity and affinity, yielding an estimated K(D) of 1.72 pM. NMR data revealed that the residues of Lys8, Leu10, Val63, Val66, Lys69 and Ala74 of IL-8 interact with aptamer. Moreover, the 8A-35 aptamer has a potent IL-8-neutralizing activity that can modulate multiple biological activities of IL-8 in human neutrophils, including migration, intracellular signaling, and intracellular Ca(2+) mobilization. Our results suggest that the 8A-35 aptamer has great potential to be a lead structure in the development of effective therapeutic agents against inflammatory diseases.

Sung|Ho Jin|HJ|
Choi|Sooho|S|
Lee|Ji Won|JW|
Ok|Chang Youp|CY|
Bae|Yoe-Sik|YS|
Kim|Yun-Hee|YH|
Lee|Weontae|W|
Heo|Kyun|K|
Kim|In-Hoo|IH|

D019906:Nuclear Magnetic Resonance, Biomolecular

Neutrophil
Aptamer
Interleukin-8 (IL-8)
Nuclear magnetic resonance (NMR)
SELEX


Metabolite of tryptophan promoting changes in EEG signal and the oxidative status of the brain.

Abstract: Tryptophan is an essential amino acid precursor of neurotransmitter serotonin and triptamine. During its metabolism, indole-3-acetic acid (IAA) is generated; this substance presents both antioxidant and prooxidant effects in different biological systems in addition to hipoglicemic effects. To date, electroencephalography (EEG) has been used to evaluate the temporal effect of several substances in neurotransmission. The goal of this study was to characterize the effect of IAA in the brain by analysing the EEG signal and evaluate the oxidative status by means of biochemical parameters. The EEG was acquired by using a noninvasive method, and the brain electric signal was analysed by advanced digital signal processing techniques to determinate the energy signal filtered in different band frequencies. Furthermore, the oxidative status of the brain was investigated by measuring the activity of antioxidant enzymes and lipid peroxidation as well as blood glucose rates of the animals treated with different doses of IAA. Our results showed the relationship of IAA administration with changes in EEG signals. The oxidative status of the brain was modified by IAA after 14 days of treatment.

Ferrari|Rosana|R|
Pugini|Silvana Maria Picolli|SM|
Arce|Aldo Ivan Cespedes|AI|
Costa|Ernane Jose Xavier|EJ|
de Melo|Mariza Pires|MP|

IAA
neurotransmission
SOD
brain electrical activity
oxidative stress


Teaching Magnetoelectric Sensing to Secondary School Students-Considerations for Educational STEM Outreach.

Abstract: A major challenge in modern society is the need to increase awareness and excitement with regard to science, technology, engineering and mathematics (STEM) and related careers directly or among peers and parents in order to attract future generations of scientists and engineers. The numbers of students aiming for an engineering degree are low compared to the options available and the workforce needed. This may, in part, be due to a traditional lack of instruction in this area in secondary school curricula. In this regard, STEM outreach programs can complement formal learning settings and help to promote engineering as well as science to school students. In a long-term outreach collaboration with scientists and engineers, we developed an outreach program in the field of magnetoelectric sensing that includes an out-of-school project day and various accompanying teaching materials. In this article, we motivate the relevance of the topic for educational outreach, share the rationales, objectives and aims, models and implementation strategies of our program and provide practical advice for those interested in outreach in the field of magnetoelectric sensing.

Broß|Cara|C| Enzingmüller|Carolin|C| Parchmann|Ilka|I| Schmidt|Gerhard|G|

ME sensors
biomagnetic sensing
interdisciplinary/multidisciplinary
medical sensing
public understanding/outreach


Interstitial 1p32.1p32.3 deletion in a patient with multiple congenital anomalies.

Abstract: Interstitial deletions encompassing chromosome bands 1p32.1p32.3 are rare. Only nine unrelated patients with partially overlapping 1p32.1p32.3 deletions of variable size and position have been reported to date. We report on a 17-month-old boy with choanal atresia, hearing loss, urogenital anomalies, and microcephaly in whom an interstitial de novo deletion of 6.4 Mb was detected in 1p32.1p32.3 (genomic position chr1:54,668,618-61,113,264 according to GRCh37/hg19). The deleted region harbors 31 RefSeq genes. Notable genes in the region are PCSK9, haploinsufficiency of which caused low LDL cholesterol plasma levels in the patient, and DAB1, which is a candidate gene for cognitive deficits, microcephaly, and cerebral abnormalities such as ventriculomegaly and agenesis of the corpus callosum. Choanal atresia, microcephaly, and severe hearing loss were previously not known to be associated with 1p32 deletions. Our reported patient thus broadens the spectrum of clinical findings in this chromosome region and further facilitates genotype-phenotype correlations. Additional patients with overlapping deletions and/or point mutations in genes of this region need to be identified to elucidate the role of individual genes for the complex clinical manifestations.

Kehrer|Martin|M| Schäferhoff|Karin|K| Bonin|Michael|M| Jauch|Anna|A| Bevot|Andrea|A| Tzschach|Andreas|A|

D048868:Adaptor Proteins, Signal Transducing

choanal atresia
hearing loss
urogenital anomalies
microcephaly
PCSK9
DAB1
NFIA
SNP-array
del1p32.1p32.3


Patient with valvular disease: evolving care patterns.

Abstract: COVID-19 has put each and every one at test. Cardiological clinics are facing constrained resources, limiting timely treatment of patients as usual. Patients with valvular heart disease are one of the most time sensitive patient populations, with delayed therapy possible leading to increased morbidity and mortality. Identifying and allocating the available resources to the most vulnerable patients is crucial in providing optimal patient care with prioritization of essential surgical or percutaneous procedures for valvular heart disease. Implementing telemedicine approaches might help to minimize non-essential physician-to-patient contact to ensure safety, for both patients and lastly but not least the treating physicians.

valvular
COVID-19
heart disease
telemedicine
coronavirus
digital health


Triple marker composed of p16, CD56, and TTF1 shows higher sensitivity than INSM1 for diagnosis of pulmonary small cell carcinoma: proposal for a rational immunohistochemical algorithm for diagnosis of small cell carcinoma in small biopsy and cytology specimens.

Abstract: Pulmonary small cell carcinoma (SCLC) can be usually diagnosed based on the morphological evaluation of routine histological or cytological preparations. However, immunohistochemistry may be also necessary in problematic cases. Insulinoma-associated 1 (INSM1) has recently been reported as a highly sensitive and specific marker that displays positivity in ~90%-100% of poorly differentiated pulmonary neuroendocrine tumors. We compared diagnostic performance of INSM1 and previously reported composite marker CD56 + p16 + thyroid transcription factor-1 (TTF1) in the diagnosis of SCLC in small biopsy specimens and cytoblocks. The composite marker CD56 + p16 + TTF1 correctly classified 100% of SCLC cases, and its sensitivity was significantly higher than the sensitivity of INSM1. Among 100 SCLC cases, CD56, TTF1, and p16 each individually classified more specimens correctly than INSM1 (CD56: 84%, TTF1: 89%, p16: 95%, INSM1: 81%); the difference was statistically significant only for p16. INSM1 showed the lowest classification agreement between paired biopsy and cytoblock specimens (κ = 0.182), whereas CD56 and p16 displayed perfect agreement (κ = 1) and TTF1 showed moderate agreement (κ = 0.4). Although INSM1 is reportedly the most specific marker of SCLC, its sensitivity is not superior to p16 or composite marker CD56 + TTF1 + p16. Based on this study, we propose the following algorithm, which, in the appropriate clinical and histological context, may be useful in establishing the correct diagnosis of SCLC: First, INSM1 detection is performed, and if the result is negative, CD56 is added, followed successively by p16 and TTF1 if all previously applied markers are negative. This approach should detect most, if not all, SCLC cases, while successively trading specificity for sensitivity.

Švajdler|Marián|M| Mezencev|Roman|R| Šašková|Bohuslava|B| Ondič|Ondrej|O| Mukenšnábl|Petr|P| Michal|Michal|M|

D019941:Cyclin-Dependent Kinase Inhibitor p16


Mouse serum protects against total body irradiation-induced hematopoietic system injury by improving the systemic environment after radiation.

Abstract: Reactive oxygen species (ROS) play a critical role in total body irradiation (TBI)-induced hematopoietic system injury. However, the mechanisms involved in ROS production in hematopoietic stem cells (HSCs) post TBI need to be further explored. In this study, we demonstrated that hematopoietic system injury in mice radiated with TBI was effectively alleviated when the blood circulation environment was changed via the injection of serum from non-radiated mice. Serum injection increased the survival of radiated mice and ameliorated TBI-induced hematopoietic system injury through attenuating myeloid skew, increasing HSC frequency, and promoting the reconstitution of radiated HSCs. Serum injection also decreased ROS levels in HSCs and regulated oxidative stress-related proteins. A serum proteome sequence array showed that proteins related to tissue injury and oxidative stress were regulated, and a serum-derived exosome microRNA sequence assay showed that the PI3K-Akt and Hippo signaling pathways were affected in radiated mice injected with serum from non-radiated mice. Furthermore, a significant increase in cell viability and a decrease in ROS were observed in radiated lineage-c-kit+ cells treated with serum-derived exosomes. Similarly, an improvement in the impaired differentiation of HSCs was observed in radiated mice injected with serum-derived exosomes. Taken together, our observations suggest that serum from non-radiated mice alleviates HSC injury in radiated mice by improving the systemic environment after radiation, and exosomes contribute to this radioprotective effect as important serum active component.

Zhang|Junling|J| Han|Xiaodan|X| Zhao|Yu|Y| Xue|Xiaolei|X| Fan|Saijun|S|

Mouse serum
Reactive oxygen species
Total body irradiation
Hematopoietic stem cells
Serum-derived exosomes
Peripheral blood systemic environment


Do stable multiply injured patients with bilateral femur fractures have higher complication rates? An investigation by the EPOFF study group.

Abstract:
BACKGROUND
Polytrauma patients with bilateral femur shaft fractures are known to have a higher rate of complications when compared with those who have sustained unilateral fractures. The current study tests the hypothesis that the high incidence of posttraumatic complications in patients who do not have a severe head or chest injury is caused by accompanying injuries rather than by the additional femur fracture.

METHODS
Inclusion criteria New Injury Severity Score > 16 points; AIS score value of the chest ≤3 points and no severe head injury. Two study groups: a unilateral group (USF group) (n = 146) and a bilateral femur shaft fracture group (BSF group) (n = 19). Endpoints monitored were length of stay in the intensive care unit, duration on a ventilator, and several postsurgical complications (e.g., SEPSIS, acute lung injury). Statistics Fisher's exact test for binary variables, and independent t-tests and regression analyses for continuous indicators of injury severity and clinical outcomes.

RESULTS
Patients with bilateral femur fractures had a significantly higher incidence of hemothorax. Moreover, they received blood transfusions more often upon admission, and exhibited a longer ICU stay (p = 0.008). However, this patient group did not exhibit a significantly higher incidence of postsurgical complications (p = 0.1) than those with unilateral fractures. After adjusting for injury severity, no difference in the length of the ICU stay was observed. Bilateral fracture patients who were in an uncertain condition preoperatively had a longer length of stay in the ICU postoperatively (p = 0.002).

CONCLUSIONS
In the absence of major head or chest injuries, patients with multiple injuries and bilateral femur shaft fractures have a similar complication rate to polytrauma patients with unilateral fractures. Moreover, an uncertain condition preoperatively was associated with an increased stay in the intensive care unit. The results support the idea that associated injuries rather than the additional femur fracture are responsible for complications during the clinical stay.

Pfeifer|Roman|R|
Rixen|Dieter|D|
Husebye|Elisabeth Ellingsen|EE|
Pardini|Dustin|D|
Müller|Michael|M|
Dumont|Clemens|C|
Oestern|Hans Georg|HG|
Giannoudis|Peter|P|
Pape|Hans-Christoph|HC|
|||

Femur fracture
Complications
Polytrauma
Risk factors


The other side of the bridge: exploring the sexual relationships of men who have sex with men and their female partners in Mumbai, India.

Abstract: Behaviourally bisexual men have been identified as a 'bridge' population of HIV transmission to heterosexual women in India. Little is known about the sexual relationships that these men have with their female sex partners. The primary objective of this study was to explore the sexual practices and relationship dynamics between married and unmarried behaviourally bisexual men and their female sex partners in Mumbai, India. In 2009, semi-structured qualitative interviews were conducted with 32 men who reported sex with men and women. Participants discussed a variety of sexual practices and arrangements with female sex partners. Irrespective of marital status and sexual identity, many said that they had satisfying sexual experiences and feelings of affection for female sex partners. However, sexual incompatibility between married partners was also reported. Explanations of bisexual concurrency were discussed in terms of both sexual satisfaction and sexual preference. Self-perceived HIV risk related to same-sex sexual behaviour motivated many men to use condoms with female partners. Expectations of unprotected marital sex and perceptions of partner risk were barriers to condom use. HIV-prevention programmes for this population may benefit from tailored risk-reduction counselling that attends to the variations of these sexual and social relationship dynamics.

Closson|Elizabeth F|EF|
Sivasubramanian|Murugesan|M|
Mayer|Kenneth H|KH|
Srivastava|Ankur|A|
Safren|Steven A|SA|
Anand|Vivek Raj|VR|
Gangakhedkar|Raman|R|
Mimiaga|Matthew J|MJ|


Influence of unilateral spatial neglect on vertical perception in post-stroke pusher behavior.

Abstract: Pusher behavior (PB) impairs verticality in the frontal plane and is often associated with unilateral spatial neglect (USN). However, it is unclear whether USN affects verticality among patients with PB. We aimed to clarify the characteristics of verticality among PB, with and without USN. The study included 43 patients with right hemisphere stroke, including 12 without PB or USN, 10 with only USN, 10 with PB only, and 11 with PB and USN, and 15 age-matched healthy individuals. The subjective visual vertical (SVV), subjective postural vertical with eyes closed (SPV), and subjective postural vertical with eyes open were assessed. Under each condition, the mean (tilt direction) and standard deviation (variability) across trials were calculated. The variability of SVV was significantly greater among patients with only USN (6.9°±5.9°) or those with PB and USN (7.6 ± 4.3°). On SPV, the contralesional tilt was significantly greater, with higher variability, in patients with only PB (-2.2°±1.1° and 6.3°±1.4°, respectively) and those with PB and USN (-2.1°±2.0° and 6.6°±2.0°, respectively) than in the other groups. In patients with PB, SVV differed depending on the presence of USN, but it was suggested that SPV might not be affected by USN. These findings are important to plan PB treatment.

Fukata|Kazuhiro|K| Amimoto|Kazu|K| Fujino|Yuji|Y| Inoue|Masahide|M| Inoue|Mamiko|M| Takahashi|Yosuke|Y| Sekine|Daisuke|D| Makita|Shigeru|S| Takahashi|Hidetoshi|H|

Unilateral spatial neglect
Pusher behavior
Stroke
Postural balance
Subjective vertical perception


BCOR-CCNB3-positive soft tissue sarcoma with round-cell and spindle-cell histology: a series of four cases highlighting the pitfall of mimicking poorly differentiated synovial sarcoma.

Abstract:
AIMS
BCOR-CCNB3 sarcoma is a genetically defined undifferentiated malignancy with Ewing sarcoma (ES)-like round cells, and preferentially affects the bones of male adolescents. Sarcomas harbouring BCOR-CCNB3 rarely arise from soft tissues; therefore, we aimed to report four cases to expand the clinicopathological spectrum.

METHODS AND RESULTS
By reverse transcription polymerase chain reaction and confirmatory sequencing, we detected a BCOR-CCNB3 transcript in primary undifferentiated sarcomas of the deep musculature of four male patients, comprising two teenagers (aged 14 and 17 years) and two adults (aged 34 and 44 years). The tumours originated in the back (n = 2), pelvis (n = 1), and thigh (n = 1), and were 70-140 mm in size (mean, 107 mm). All tumours showed sheets of primitive round or ovoid cells with vesicular nuclei, active mitosis (28-41/10 high-power fields), variably prominent nucleoli, and geographical necrosis. This major component transformed into fascicles of elongated spindle cells with staghorn vessels and a myxoid reticular stroma, accounting for 10-50% of areas. All cases were positive for CD99, three were positive for TLE1, and one was positive for EMA, indicating poorly differentiated synovial sarcomas (PDSSs). Nuclear cyclin B3 reactivity was present in all cases, but not in molecularly confirmed atypical ESs and PDSSs. At the last follow-up (median, 13.5 months), one patient had died of lung metastasis, two were alive with tumours, and one was tumour-free.

CONCLUSIONS
BCOR-CCNB3-positive sarcomas may primarily occur in soft tissues of adults and show PDSS-mimicking round-cell and spindle-cell histology with aggressive behaviour. Cyclin B3 is useful for selecting candidates for BCOR-CCNB3 molecular testing.

Li|Wan-Shan|WS|
Liao|I-Chuang|IC|
Wen|Mei-Chin|MC|
Lan|Howard Haw-Chang|HH|
Yu|Shih-Chen|SC|
Huang|Hsuan-Ying|HY|

D020133:Reverse Transcriptase Polymerase Chain Reaction

synovial sarcoma
BCOR-CCNB3
Ewing sarcoma
round
spindle


Diagnostic Accuracy of Dynamic Contrast Enhanced Magnetic Resonance Imaging in Characterizing Lung Masses.

Abstract:
BACKGROUND
Imaging plays a critical role not only in the detection, but also in the characterization of lung masses as benign or malignant.

OBJECTIVES
To determine the diagnostic accuracy of dynamic magnetic resonance imaging (MRI) in the differential diagnosis of benign and malignant lung masses.

PATIENTS AND METHODS
Ninety-four masses were included in this prospective study. Five dynamic series of T1-weighted spoiled gradient echo (FFE) images were obtained, followed by a T1-weighted FFE sequence in the late phase (5th minutes). Contrast enhancement patterns in the early (25th second) and late (5th minute) phase images were evaluated. For the quantitative evaluation, signal intensity (SI)-time curves were obtained and the maximum relative enhancement, wash-in rate, and time-to-peak enhancement of masses in both groups were calculated.

RESULTS
The early phase contrast enhancement patterns were homogeneous in 78.2% of the benign masses, while heterogeneous in 74.4% of the malignant tumors. On the late phase images, 70.8% of the benign masses showed homogeneous enhancement, while most of the malignant masses showed heterogeneous enhancement (82.4%). During the first pass, the maximum relative enhancement and wash-in rate values of malignant masses were significantly higher than those of the benign masses (P = 0.03 and 0.04, respectively). The cutoff value at 15% yielded a sensitivity of 85.4%, specificity of 61.2%, and positive predictive value of 68.7% for the maximum relative enhancement.

CONCLUSION
Contrast enhancement patterns and SI-time curve analysis of MRI are helpful in the differential diagnosis of benign and malignant lung masses.

Inan|Nagihan|N|
Arslan|Arzu|A|
Donmez|Muhammed|M|
Sarisoy|Hasan Tahsin|HT|

Contrast Enhancement
Magnetic Resonance Imaging
Lung
Dynamic Imaging
Neoplasm


Epigenetic regulation by BAF (mSWI/SNF) chromatin remodeling complexes is indispensable for embryonic development.

Abstract: The multi-subunit chromatin-remodeling SWI/SNF (known as BAF for Brg/Brm-associated factor) complexes play essential roles in development. Studies have shown that the loss of individual BAF subunits often affects local chromatin structure and specific transcriptional programs. However, we do not fully understand how BAF complexes function in development because no animal mutant had been engineered to lack entire multi-subunit BAF complexes. Importantly, we recently reported that double conditional knock-out (dcKO) of the BAF155 and BAF170 core subunits in mice abolished the presence of the other BAF subunits in the developing cortex. The generated dcKO mutant provides a novel and powerful tool for investigating how entire BAF complexes affect cortical development. Using this model, we found that BAF complexes globally control the key heterochromatin marks, H3K27me2 and -3, by directly modulating the enzymatic activity of the H3K27 demethylases, Utx and Jmjd3. Here, we present further insights into how the scaffolding ability of the BAF155 and BAF170 core subunits maintains the stability of BAF complexes in the forebrain and throughout the embryo during development. Furthermore, we show that the loss of BAF complexes in the above-described model up-regulates H3K27me3 and impairs forebrain development and embryogenesis. These findings improve our understanding of epigenetic mechanisms and their modulation by the chromatin-remodeling SWI/SNF complexes that control embryonic development.

Nguyen|Huong|H|
Sokpor|Godwin|G|
Pham|Linh|L|
Rosenbusch|Joachim|J|
Stoykova|Anastassia|A|
Staiger|Jochen F|JF|
Tuoc|Tran|T|

D042002:Chromatin Assembly and Disassembly

D056484:Jumonji Domain-Containing Histone Demethylases

epigenetics
Chromatin remodeling
embryogenesis
BAF (mSWI/SNF) complexes
H3K27me2/3
brain development


Top Ten Tips Palliative Care Clinicians Should Know About Physical Medicine and Rehabilitation.

Abstract: Physical medicine and rehabilitation (PM&R) is a specialty of medicine focused on optimizing function and quality of life for individuals with physical impairments, injuries, or disabling illnesses. Given the sometimes acute nature of the loss of function and even loss of independence, there are significant palliative care (PC) needs within patients seen by PM&R. This article, written by a team of PM&R and PC specialists, aims to help the PC team better understand the world of postacute care, expand their toolkit for treating musculoskeletal and neurological symptoms, improve prognostication for patients with brain and spinal cord injuries, and decide when patients may benefit from PM&R consultation and support. There is significant overlap between the populations treated by PM&R and PC. Better integration between these specialties will help patients to maintain independence as well as advance excellent patient-centered care.

Brassil|Michelle E|ME|
Cheville|Andrea|A|
Zheng|Jasmine Y|JY|
Smith|Sean R|SR|
Tolchin|Dorothy W|DW|
Wittry|Sarah A|SA|
Jones|Christopher A|CA|
Chernack|Betty|B|

D064946:Hospice and Palliative Care Nursing

D010810:Physical and Rehabilitation Medicine

physical medicine and rehabilitation
function
postacute care
neurological compromise
serious illness
spasticity management
traumatic brain injury
traumatic spinal cord injury


Evaluation on Long-Term Test-Retest Reliability of the Short-Form Childhood Trauma Questionnaire in Patients with Schizophrenia.

Abstract:
Background
Many studies have reported an association between childhood trauma exposure and schizophrenia. Among these studies, the Short-form Childhood Trauma Questionnaire (CTQ-SF) is one of the most widely used measures of childhood trauma. However, little is known regarding the long-term reliability of the CTQ-SF, especially in patients with psychopathology.

Methods
The CTQ-SF was administered to 50 patients diagnosed with schizophrenia from a hospital in Changsha, Hunan, China. These patients were asked to re-complete the CTQ-SF when they were re-hospitalized or received outpatient treatments in the same hospital within 4 years of follow-up. Intraclass correlation coefficient (ICC) was used to assess test-retest reliability of the CTQ-SF over the intervals. Associations of the CTQ-SF with the Positive and Negative Syndrome Scale (PANSS) and Wechsler Adult Intelligence Scale (WAIS) were tested using Spearman correlation coefficients.

Results
Among the participants, 35 (70.0%) patients re-completed the CTQ-SF after an interval averaging 11.26 months. Excellent test-retest reliabilities (with ICC > 0.75) were found for the total CTQ-SF score (ICC = 0.772) as well as scores of the emotional abuse (ICC = 0.808), physical abuse (ICC = 0.756), sexual abuse (ICC = 0.877) and physical neglect (ICC = 0.751) subscales. Meanwhile, a moderate test-retest reliability was found for the emotional neglect subscale (ICC = 0.538). At both baseline and follow-up, no significant correlations (p > 0.05) were found between CTQ-SF scores and any other clinical assessments.

Conclusion
Our results suggest that CTQ-SF is reliable to assess childhood trauma exposures in schizophrenia over relatively long intervals, regardless of patients' current symptoms and states of cognition.

Xiang|Zhibiao|Z| Liu|Zhening|Z| Cao|Hengyi|H| Wu|Zhipeng|Z| Long|Yicheng|Y|

childhood trauma
childhood trauma questionnaire
schizophrenia
childhood adversity
test–retest reliability


Comparative analysis of actigraphy performance in healthy young subjects.

Abstract: Sleep-related health disorders are increasing worldwide; diagnosis and treatment of such sleep diseases are commonly invasive and sometimes unpractical or expensive. Actigraphy has been recently introduced as a tool for the study of sleep and circadian disorders; however, there are several devices that claim to be useful for research and have not been thoroughly tested. This comparative study provides activity, sleep and temperature information regarding several of the most commonly used actigraphers: Micro-Mini Motion Logger; Act Trust; Misfit Flash; Fitbit Flex & Thermochron. Twenty-two healthy young subjects were assessed with five different commercial actigraphs (Micro-Mini Motionlogger Watch, Condor Act Trust, MisFit Flash and Fitbit Flex) and a temperature recorder (Thermochron), and also completed a sleep diary for a week. There were not significant differences in the analysis of rest-activity pattern between devices. Temperature rhythm comparison between the Act Trust and the Thermochron showed significant differences in rhythm percentage (p<0.05) and mesor (p<0.0563) but not in amplitude or acrophase. Although data accessibility and ease of use was very different for the diverse devices, there were no significant differences for sleep onset, total sleep time and sleep efficiency recordings, where applicable. In conclusion, depending on the type of study and analysis desired (as well as cost and compliance of use), we propose some relative advantages for the different actigraphy/temperature recording devices.

Bellone|Giannina J|GJ|
Plano|Santiago A|SA|
Cardinali|Daniel P|DP|
Chada|Daniel Pérez|DP|
Vigo|Daniel E|DE|
Golombek|Diego A|DA|

Actigraphy
Sleep
Circadian
Temperature
Rest-activity
Ambulatory monitoring


Occurrence of Multidrug-resistant Uropathogens Implicated in Asymptomatic Bacteriuria in Adults with Sickle Cell Disease in Ile-Ife, Southwest Nigeria.

Abstract:
Objectives
We sought to determine the prevalence of asymptomatic bacteriuria (ASB) in patients with sickle cell disease (SCD), the susceptibility profile of its agents and their extended-spectrum β-lactamase (ESBL) production.

Methods
Fifty-nine patients with SCD and 116 healthy controls were investigated. Urine samples were collected and cultured by standard techniques. We used the disc diffusion technique to determine antibiotic susceptibility. ESBL was detected by the combination disc method and detection of bla SHV, bla TEM, and bla CTX-M genes by multiplex-polymerase chain reaction.

Results
The prevalence of ASB was higher among patients with SCD (8.6%) than controls (0.9%) (p = 0.016), predominantly among females. Coagulase-negative staphylococci (n = 2; 33.3%) predominated among the isolates. Other uropathogens included Stenotrophomonas maltophilia, Acinetobacter baumannii, and Enterobacter cloacae. All isolates were sensitive to meropenem but were resistant to ceftazidime, ampicillin, and tetracycline. bla SHV, bla TEM, and bla CTX-M-15 were detected in Enterobacter cloacae.

Conclusions
The prevalence of ASB is high in patients with SCD predominantly among females. Rare multidrug-resistant uropathogens were implicated. We posit a need for resistance surveillance programs and antibiotic stewardship to prevent treatment failure and reduce drug resistance.

Bacteriuria
Drug Resistance
Anemia, Sickle Cell
Anti-Bacterial Agents


Safety of parathyroidectomy in older vs. younger patients with primary hyperparathyroidism.

Abstract:
Background
Primary hyperparathyroidism is a prevalent endocrinopathy for which surgery is the only curative option. Parathyroidectomy is primarily recommended in younger and symptomatic patients, while there are still concerns regarding surgical complications in older patients. We therefore assessed the association of age with surgical outcomes in patients undergoing parathyroidectomy in a large population in Switzerland.

Methods
Population-based cohort study of adult patients with primary hyperparathyroidism undergoing parathyroidectomy in Switzerland between 2012 and 2018. The cohort was divided into four age groups (<50 years, 50-64 years, 65-74 years, ≥75 years). The primary outcome was a composite of in-hospital postoperative complications. Secondary outcomes were intensive care unit (ICU) admission, unplanned 30-day-readmission, and prolonged length of hospital stay.

Results
We studied 2642 patients with a median (IQR) age of 62 (53-71) years. Overall, 111 patients had complications including surgical re-intervention, hypocalcemia, and vocal cord paresis. As compared to <50 year-old patients, older patients had no increased risk for in-hospital complications after surgery (50-64 years: odds ratio (OR): 0.51 (95% CI, 0.28 to 0.92); 65-74 years: OR: 0.72 (95% CI, 0.39 to 1.33); ≥75 years: OR: 1.03 (95% CI, 0.54 to 1.95), respectively. There was also no association of age and rates of ICU-admission and unplanned 30-day-readmission, but oldest patients had longer hospital stays (OR: 2.38 (95% CI, 1.57 to 3.60)).

Conclusion
≥50 year-old patients undergoing parathyroidectomy had comparable risk of in-hospital complications as compared with younger ones. These data support parathyroidectomy in even older patients with primary hyperparathyroidism as performed in clinical routine.

Mueller|Marlena|M|
Ebrahimi|Fahim|F|
Christ|Emanuel|E|
Nebiker|Christian Andreas|CA|
Schuetz|Philipp|P|
Mueller|Beat|B|
Kutz|Alexander|A|0000-0002-7549-5648

parathyroidectomy
primary hyperparathyroidism
older patients
age
outcome
postoperative complications


Extension of the association structure in joint models to include weighted cumulative effects.

Abstract: Motivated by a study measuring diabetes-related risk factors and complications, we postulate an extension to the standard formulation of joint models for longitudinal and survival outcomes, wherein the longitudinal outcome has a cumulative effect on the hazard of the event, weighted by recency. We focus on the relationship between the biomarker HbA1c and the development of sight threatening retinopathy, since the impact of the HbA1c marker on the risk of sight threatening retinopathy is expected to be cumulative, with the evolution of the HbA1c marker over time contributing to progressively greater damage to the vascular structure of the retina. Opting for a parametric approach, we propose the use of the normal and skewed normal probability density functions as weight functions, estimating the relevant parameters directly from the data. The use of the recency-weighted cumulative effect specification allows us to incorporate differences in the development of the longitudinal profile over time in the calculation of hazard ratios between subjects. The proposed functions provide us with parameters with clinically relevant interpretations while retaining a degree of flexibility. In addition, they also allow answering of important clinical questions regarding the relative importance of various segments of the biomarkers history in the estimation of the risk of the event. Copyright © 2017 John Wiley & Sons, Ltd.

D001499:Bayes Theorem
D015415:Biomarkers
D015331:Cohort Studies
D003198:Computer Simulation
D048909:Diabetes Complications
D003920:Diabetes Mellitus
D003930:Diabetic Retinopathy
D006442:Glycated Hemoglobin A
D006801:Humans
D008137:Longitudinal Studies
D008390:Markov Chains
D015233:Models, Statistical
D016016:Proportional Hazards Models
D018570:Risk Assessment
D012307:Risk Factors
D013534:Survival

association structures
joint models
survival outcome
longitudinal outcome


COVID-19 detection method based on SVRNet and SVDNet in lung x-rays.

Abstract: Purpose: To detect and diagnose coronavirus disease 2019 (COVID-19) better and faster, separable VGG-ResNet (SVRNet) and separable VGG-DenseNet (SVDNet) models are proposed, and a detection system is designed, based on lung x-rays to diagnose whether patients are infected with COVID-19. Approach: Combining deep learning and transfer learning, 1560 lung x-ray images in the COVID-19 x-ray image database (COVID-19 Radiography Database) were used as the experimental data set, and the most representative image classification models, VGG16, ResNet50, InceptionV3, and Xception, were fine-tuned and trained. Then, two new models for lung x-ray detection, SVRNet and SVDNet, were proposed on this basis. Finally, 312 test set images (including 44 COVID-19 and 268 normal images) were used as input to evaluate the classification accuracy, sensitivity, and specificity of SVRNet and SVDNet models. Results: In the classification experiment of lung x-rays that tested positive and negative for COVID-19, the classification accuracy, sensitivity, and specificity of SVRNet and SVDNet are 99.13%, 99.14%, 99.12% and 99.37%, 99.43%, 99.31%, respectively. Compared with the VGG16 network, SVRNet and SVDNet increased by 3.07%, 2.84%, 3.31% and 3.31%, 3.13%, 3.50%, respectively. On the other hand, the parameters of SVRNet and SVDNet are  and  , respectively. These are 61.56% and 55.31% less than VGG16, respectively. Conclusions: The SVRNet and SVDNet models proposed greatly reduce the number of parameters, while improving the accuracy and increasing the operating speed, and can accurately and quickly detect lung x-rays containing COVID-19.

COVID-19
deep learning
transfer learning
x-ray images


Determination of the Structures of Uranyl-Tri-n-butyl-Phosphate Aggregates by Coupling Experimental Results with Molecular Dynamic Simulations.

Abstract: The complex structure of a plutonium uranium refining by extraction (PUREX) process organic phase was characterized by combining results from experiments and molecular dynamics simulations. For the first time, the molecular interactions between tri-n-butyl phosphate (TBP) and the extracted solutes, as well as TBP aggregation after the extraction of water and/or uranyl nitrate, were described and analyzed concomitantly. Coupling molecular dynamics simulations with small- and wide-angle X-ray scattering (SWAXS) experiments can lead to simulated organic solutions that are representative of the experimental ones, even for high extractant and solute concentrations. Furthermore, this coupling is well adapted for the interpretation of SWAXS experiments without preliminary hypothesis on the size or shape of aggregates. The results link together previous literature studies obtained for each level of depiction separately (complexation or aggregation). Without uranium, or at low metal concentration, almost no aggregation was observed. At high uranium concentration, organic phases contain small [UO2 (NO3 )2 (TBP)2 ]n polymetallic aggregates (with n=2 to 4), in which the 1:2 U/TBP stoichiometry is preserved.

aggregation
molecular dynamics
uranium
solvent extraction
structure elucidation


Facial masculinity does not appear to be a condition-dependent male ornament and does not reflect MHC heterozygosity in humans.

Abstract: Recent studies have called into question the idea that facial masculinity is a condition-dependent male ornament that indicates immunocompetence in humans. We add to this growing body of research by calculating an objective measure of facial masculinity/femininity using 3D images in a large sample (n = 1,233) of people of European ancestry. We show that facial masculinity is positively correlated with adult height in both males and females. However, facial masculinity scales with growth similarly in males and females, suggesting that facial masculinity is not exclusively a male ornament, as male ornaments are typically more sensitive to growth in males compared with females. Additionally, we measured immunocompetence via heterozygosity at the major histocompatibility complex (MHC), a widely-used genetic marker of immunity. We show that, while height is positively correlated with MHC heterozygosity, facial masculinity is not. Thus, facial masculinity does not reflect immunocompetence measured by MHC heterozygosity in humans. Overall, we find no support for the idea that facial masculinity is a condition-dependent male ornament that has evolved to indicate immunocompetence.

Zaidi|Arslan A|AA|0000-0002-2155-8367
White|Julie D|JD|0000-0002-2235-4817
Mattern|Brooke C|BC|
Liebowitz|Corey R|CR|
Puts|David A|DA|
Claes|Peter|P|
Shriver|Mark D|MD|

facial masculinity
MHC heterozygosity
human evolution
immunocompetence handicap hypothesis
sexual selection


Overexpression of ULK1 Represents a Potential Diagnostic Marker for Clear Cell Renal Carcinoma and the Antitumor Effects of SBI-0206965.

Abstract:
BACKGROUND
Uncoordinated 51-like kinase 1 (ULK1) plays a vital role in autophagy. ULK1 dysregulation has recently been found in several human cancers.

METHODS
mRNA expression levels of ULK1 and clinical information were analysed from The Cancer Genome Atlas data. ULK1 expression levels were verified in 36 paired fresh ccRCC tissue specimens by western blot analysis. Expression of ULK1 was knockdown by shRNA lentivirus. ULK1 activity was inhibited by SBI-0206965. The effect of inhibition of ULK1 was measured by detecting the apoptotic rate, autophagy, and the ratio of ROS and NADPH. The efficacy of SBI-0206965 in vivo was assessed by the murine xenograft model.

FINDINGS
ULK1 mRNA expression was significantly upregulated in clear cell renal cell carcinoma (ccRCC) and overexpression of ULK1 correlated with poor outcomes. We found that ULK1 was highly expressed in 66.7% of ccRCC tumours (p < 0·05). Knockdown of ULK1 and selective inhibition of ULK1 by SBI-0206965 induced cell apoptosis in ccRCC cells. We demonstrated that SBI-0206965 triggered apoptosis by preventing autophagy and pentose phosphate pathway (PPP) flux. Furthermore, blocking the kinase activity of ULK1 with SBI-0206965 resulted in a level of anticancer effect in vivo.

INTERPRETATION
Taken together, our results suggested that ULK1 was upregulated in ccRCC tumours and may be a potential therapeutic target. Therefore, SBI-0206965 should be further considered as an anti-ccRCC agent. FUND: This work was supported in part by The National Natural Science Foundation of China (No. 81570748) and Natural Science Foundation of Fujian Province (No. 2018J01345, 2017XQ1194).

Lu|Jun|J| Zhu|Ling|L| Zheng|Luo-Ping|LP| Cui|Qiang|Q| Zhu|He-Huan|HH| Zhao|Hu|H| Shen|Zhou-Ji|ZJ| Dong|Hui-Yue|HY| Chen|Shu-Shang|SS| Wu|Wei-Zhen|WZ| Tan|Jian-Ming|JM|

D047908:Intracellular Signaling Peptides and Proteins


Quad Council Coalition community/public health nursing competencies: Building consensus through collaboration.

Abstract:
BACKGROUND
The changing professional environment for community/public health nursing practice necessitates competencies grounded in current evidence-based practice. The Quad Council Coalition (QCC) appointed a Task Force to revise the 2011 QCC Competencies for Public Health Nursing. The goal of the competencies is to guide professional nursing practice, curricula, research, and policy development. This paper describes the process used to develop the revised 2018 Competencies.

METHODS
A biphasic Delphi technique was used to conduct a detailed examination and build consensus. Four individuals representing community/public health practice and education collaborated to identify and implement a systematic process for revising the QCC Competencies. The process included multiple iterations of review and feedback using consistent methods and tools to analyze and synthesize themes.

RESULTS
The primary result of this project is the 2018 QCC Competencies document that has strong consensus and provides a coherent voice from professionals on the practice of community/public health nursing.

DISCUSSION
Use of current QCC Competencies will strengthen the community/public health nursing capacity to positively impact the health and well-being of populations.

D002983:Clinical Competence
D003152:Community Health Nursing
D003162:Competency-Based Education
D032921:Consensus
D003479:Curriculum
D003697:Delphi Technique
D006801:Humans
D011634:Public Health
D011637:Public Health Nursing

competency
practice
research
policy
education
community-public health nurse
critical behaviors
domain
evaluation


Age structure of bed bug (Heteroptera: Cimicidae) aggregations affects the nymphal feeding success.

Abstract:
BACKGROUND
Bed bugs (Heteroptera: Cimicidae) are a group of blood-feeding ectoparasites. They mainly specialize on bats and birds, but a few species are important human pests. They exhibit several unique adaptations for their parasitic lifestyle. Among those, bed bug aggregations represent a striking example of a sub-social structure. However, their benefits for the bed bugs as well as their potential for bed bug control are largely unexplored. Young nymphs are known to disperse from the aggregations much less than older ones or adults. We therefore found possible that the aggregation age structure is connected with success in finding host and tested the effect of presence of adults on nymphal feeding success.

RESULTS
We tested the effect of presence of adults on feeding success of first-instar nymphs using an artificial feeding system. We found that presence of fed adults causes larger proportion of nymphs to feed.

CONCLUSIONS
Based on our data, fed bed bugs seem to trigger the young nymphs to actively forage. Since the first instar is much less viable than later stages, our finding points to an adaptive behavior that economizes on foraging energy cost. In the context of bed bug control, knowledge on such behavior emphasizes the prevention of fed bed bugs from returning to harborages. Bed bug traps may thus be used not just as means of bed bug monitoring, but also as means of control.

Bed bug
Aggregation
Feeding
Sub-social structure


Thought Leader Comparisons of Risks in Precision Medicine Research.

Abstract: Biomedical research is increasingly capitalizing on an array of data to illuminate the interplay between "omics," lifestyle, and health. Leveraging this information presents opportunities to advance knowledge but also poses risks to research participants. In interviews with thought leaders, we asked which data type associated with a hypothetical precision medicine research endeavor was riskiest: 42% chose ongoing access to electronic health records, 17% chose genomic analyses of biospecimens, and 15% chose streaming data from mobile devices. Other responses included "It depends" (15%), the three types are equally risky (8%), and the combination of data types together is riskiest (3%). When asked to consider the hypothetical study overall, 60% rated the likelihood of the risks materializing as low, but 20% rated the potential consequences as severe. These results have implications for study design and informed consent, including placing appropriate emphasis on the risks and protections for the full range of data.

Beskow|Laura M|LM|
Hammack-Aviran|Catherine M|CM|
Brelsford|Kathleen M|KM|

D035843:Biomedical Research
D057286:Electronic Health Records
D006801:Humans
D007258:Informed Consent
D007857:Leadership
D057285:Precision Medicine
D012107:Research Design
D018570:Risk Assessment

electronic health records
informed consent
big data
genomic research
research ethics


Neuropeptide Y expression marks partially differentiated β cells in mice and humans.

Abstract: β Cells are formed in embryonic life by differentiation of endocrine progenitors and expand by replication during neonatal life, followed by transition into functional maturity. In this study, we addressed the potential contribution of neuropeptide Y (NPY) in pancreatic β cell development and maturation. We show that NPY expression is restricted from the progenitor populations during pancreatic development and marks functionally immature β cells in fetal and neonatal mice and humans. NPY expression is epigenetically downregulated in β cells upon maturation. Neonatal β cells that express NPY are more replicative, and knockdown of NPY expression in neonatal mouse islets reduces replication and enhances insulin secretion in response to high glucose. These data show that NPY expression likely promotes replication and contributes to impaired glucose responsiveness in neonatal β cells. We show that NPY expression reemerges in β cells in mice fed with high-fat diet as well as in diabetes in mice and humans, establishing a potential new mechanism to explain impaired β cell maturity in diabetes. Together, these studies highlight the contribution of NPY in the regulation of β cell differentiation and have potential applications for β cell supplementation for diabetes therapy.

Rodnoi|Pope|P|
Rajkumar|Mohan|M|
Moin|Abu Saleh Md|ASM|
Georgia|Senta K|SK|
Butler|Alexandra E|AE|
Dhawan|Sangeeta|S|


Trends in Methamphetamine Use Among Men Who Have Sex with Men in New York City, 2004-2017.

Abstract: Methamphetamine (meth) use among men who have sex with men (MSM) has been documented to be associated with HIV transmission among those who are HIV-negative and worsening HIV outcomes among those who are HIV-positive. Recent media reports have suggested recent increases in meth use in New York City (NYC), particularly among Hispanic/Latino and Black MSM. Using serial cross-sectional data from 2004 to 2017, we aim to describe trends in meth use and describe racial/ethnic patterns among MSM in NYC. Overall, we observed a decrease in meth use among MSM from 2004 to 2011 and an increase from 2011 to 2017. When stratified by race/ethnicity, use among White MSM decreased. Beginning in 2008, use among both Hispanic/Latino and Black MSM increased over time. These data provide more evidence that meth use may be increasing in Hispanic/Latino and Black MSM. Culturally-tailored and status-neutral interventions should be explored.

D003430:Cross-Sectional Studies
D015658:HIV Infections
D006630:Hispanic or Latino
D018451:Homosexuality, Male
D006801:Humans
D008297:Male
D008694:Methamphetamine
D009519:New York City
D000072339:Sexual and Gender Minorities

Men who have sex with men
Meth
HIV
Disparities


Treatment of pustular psoriasis with anakinra: a statistical analysis plan for stage 1 of an adaptive two-staged randomised placebo-controlled trial.

Abstract:
BACKGROUND
Palmoplantar pustulosis (PPP) is a rare, chronic inflammatory skin disease. It is known to affect quality of life at a level comparable to that from major medical and psychiatric illness, yet current treatment options are remarkably limited. Recent evidence however suggests that interleukin-1 (IL-1) blockade with anakinra will deliver therapeutic benefit in PPP.

METHODS
Anakinra for Pustular psoriasis: Response in a Controlled Trial (APRICOT) is a two-staged, adaptive, double-blind, randomised placebo-controlled trial which aims to test the hypothesis that IL-1 blockade with anakinra will deliver therapeutic benefit in PPP. During stage 1 a total of 24 patients will be randomised (1:1) to receive either placebo or anakinra. The two candidate primary outcomes are fresh pustule count (across palms and soles) and the Palmoplantar Pustulosis Area and Severity Index (PPPASI) score, recorded at baseline and at weeks 1, 4 and 8. Analysis at the end of stage 1 will compare treatment arms to ensure sufficient efficacy and safety in order to progress to stage 2. The primary outcome for stage 2 will also be identified following an assessment of the reliability and discriminative ability of fresh pustule count and PPPASI. The trial is powered to detect efficacy and will recruit an additional 40 patients in stage 2 (n = 64 in total). Analysis will follow the intention-to-treat principle and analyse patients as randomised.

DISCUSSION
This manuscript describes the important features of the small population trial design for APRICOT and the pre-specified statistical analysis plan for stage 1. The statistical analysis plan has been developed prior to data extraction and in compliance with international guidelines. It will increase the transparency of the data analysis for the APRICOT trial. The findings of the trial will help to clarify the role of anakinra in the treatment of PPP.

TRIAL REGISTRATION
ISCRTN, ISCRTN13127147 . Registered on 1 August 2016. EudraCT Number 2015-003600-23 . Registered on 1 April 2016.

D000075522:Adaptive Clinical Trials as Topic

D053590:Interleukin 1 Receptor Antagonist Protein

D016032:Randomized Controlled Trials as Topic

Psoriasis
Anakinra
Statistical analysis plan
Palmoplantar pustulosis
Adaptive trial
Randomised controlled trial


Lower urinary tract symptoms in patients with Mayer-Rokitansky-Kuster-Hauser syndrome after neo-vagina creation by Davydov's procedure.

Abstract:
INTRODUCTION
Lower urinary tract symptoms (LUTS) in subjects with Mayer-Rokitansky-Küster-Hauser syndrome treated by Davydov's laparoscopic neo-vaginoplasty were measured.

METHODS
Davydov's laparoscopic neo-vaginoplasty was undertaken at the Department of Obstetrics/gynecology, San Raffaele Hospital, Milan, Italy, from November 2015 to July 2017, by two highly qualified surgeons. All women completed the ICIQ-UI Short Form questionnaire before and after treatment. LUTS were scored at recruitment, hospitalization, and 1, 3, 6 and 12 months after surgery.

RESULTS
Twenty-one women (mean age 21 years ± 5.9) were operated on with no major complications. Mean surgery duration was 79 min (± 55 min). Before the operation, one patient (1/21; 4.8%) reported occasional urinary loss that persisted after surgery and throughout 12 months of follow-up. After the operation, one patient (1/21; 4.8%) had urinary retention, requiring self-catheterization for 2 weeks. One month after surgery, stress incontinence was recorded in one case (1/19; 5.2%) and urge incontinence in two cases (2/19; 10.5%). At 3-month follow-up, these three patients were free of symptoms.

CONCLUSION
The rate of LUTS is lower than that reported by others using alternative surgical procedures. To the best of our knowledge, this is the first report validating LUTS after Davydov's neo-vaginoplasty.

Baruch|Yoav|Y|
Nale|Roberta|R|
Parma|Marta|M|
Di Fatta|Simona|S|
Fedele|Luigi|L|
Candiani|Massimo|M|
Salvatore|Stefano|S|

D058489:46, XX Disorders of Sex Development

Mayer-Rokitansky-Küster-Hauser syndrome
Davydov’s procedure
Neovagina
Vaginal agenesis


Ecdysteroids: A novel class of anabolic agents?

Abstract: Increasing numbers of dietary supplements with ecdysteroids are marketed as "natural anabolic agents". Results of recent studies suggested that their anabolic effect is mediated by estrogen receptor (ER) binding. Within this study the anabolic potency of ecdysterone was compared to well characterized anabolic substances. Effects on the fiber sizes of the soleus muscle in rats as well the diameter of C2C12 derived myotubes were used as biological readouts. Ecdysterone exhibited a strong hypertrophic effect on the fiber size of rat soleus muscle that was found even stronger compared to the test compounds metandienone (dianabol), estradienedione (trenbolox), and SARM S 1, all administered in the same dose (5 mg/kg body weight, for 21 days). In C2C12 myotubes ecdysterone (1 µM) induced a significant increase of the diameter comparable to dihydrotestosterone (1 µM) and IGF 1 (1.3 nM). Molecular docking experiments supported the ERβ mediated action of ecdysterone. To clarify its status in sports, ecdysterone should be considered to be included in the class "S1.2 Other Anabolic Agents" of the list of prohibited substances of the World Anti-Doping Agency.

Parr|M K|MK|
Botrè|F|F|
Naß|A|A|
Hengevoss|J|J|
Diel|P|P|
Wolber|G|G|

ecdysteroids
anabolic effect
beta-ecdysone
doping in sport
estrogen receptor beta
muscle hypertrophy


The Top 100 Cited Papers in Health Care Disparities: a Bibliometric Analysis.

Abstract: Health care disparities research is an exponentially growing and multi-faceted field. Our objective was to identify and analyze the top 100 cited articles in health care disparities. The authors searched the Thomas Reuters Web of Science for citations of all research papers (articles) relevant to health care disparities. After analyzing search results, the number of citations, authorship, year, journal, country of publication, institution of publication, and relevant topic were recorded for each article. The most cited article was Martin's 2002 work identifying the demography of incidence and occurrence of sepsis with specific analysis of race, sex, and disposition of US patients. The second most cited article was Kamangar's 2006 paper outlining geographic patterns in cancer incidence, mortality, and prevalence. The third most cited article was Williams' 1996 study determining the differences in US health patterns in populations of different races and socioeconomic statuses through a review of similar studies. The majority of articles originated in the USA (91). The journal with the most published articles was JAMA-The Journal of the American Medical Association (14). The second most cited journal was The New England Journal of Medicine (7). Most articles were published in the 2000s (84). In descending order, the 3 most common topics were (1) disparities in cancer incidence, screening, treatment, and mortality, (2) disparities in mental health treatment, and (3) physician concordance, cultural competency, and relationships with minority patients. Overall, the highly cited articles contain current advancements in the body of knowledge used to resolve health care disparities in race, ethnicity, socioeconomic status, gender, age, wealth, education level, mental health, and geography throughout the world.

Health care disparities
Bibliometric
Citations
Journals
Publications
Racial disparities