Understanding the co-evolutionary molecular mechanisms of resistance in the HIV-1 Gag and protease.

Abstract: Due to high human immunodeficiency virus type 1 (HIV-1) subtype C infections coupled with increasing antiretroviral treatment failure, the elucidation of complex drug resistance mutational patterns arising through protein co-evolution is required. Despite the inclusion of potent protease inhibitors Lopinavir (LPV) and Darunavir (DRV) in second- and third-line therapies, many patients still fail treatment due to the accumulation of mutations in protease (PR) and recently, Gag. To understand the co-evolutionary molecular mechanisms of resistance in the HIV-1 PR and Gag, we performed 100 ns molecular dynamic simulations on multidrug resistant PR's when bound to LPV, DRV or a mutated A431V NC|p1 Gag cleavage site (CS). Here we showed that distinct changes in PR's active site, flap and elbow regions due to several PR resistance mutations (L10F, M46I, I54V, L76V, V82A) were found to alter LPV and DRV drug binding. However, binding was significantly exacerbated when the mutant PRs were bound to the NC|p1 Gag CS. Although A431V was shown to coordinate several residues in PR, the L76V PR mutation was found to have a significant role in substrate recognition. Consequently, a greater binding affinity was observed when the mutated substrate was bound to an L76V-inclusive PR mutant (Gbind: -62.46 ± 5.75 kcal/mol) than without (Gbind: -50.34 ± 6.28 kcal/mol). These data showed that the co-selection of resistance mutations in the enzyme and substrate can simultaneously constrict regions in PR's active site whilst flexing the flaps to allow flexible movement of the substrate and multiple, complex mechanisms of resistance to occur. Communicated by Ramaswamy H. Sarma.

HIV-1 Gag and protease
co-evolution
protease inhibitors
molecular dynamic simulations
Antiretroviral drug resistance


Grass tablet sublingual immunotherapy downregulates the TH2 cytokine response followed by regulatory T-cell generation.

Abstract:
BACKGROUND
Sublingual administration of Phleum pratense allergen immunotherapy (SLIT) tablets is a clinically efficient treatment for grass pollen-induced rhinoconjunctivitis. This immunotherapy downregulates TH2 immune responses, induces tolerogenic pathways, and increases regulatory T cells. However, associated immune response markers of allergen desensitization remain undefined.

OBJECTIVE
We sought to characterize the kinetics of individual changes in the immunologic response to grass tablet SLIT.

METHODS
We evaluated the systemic effects of SLIT in a longitudinal analysis of humoral and cellular immune parameters in peripheral blood samples.

RESULTS
Grass tablet SLIT administration induced a 2-phase systemic humoral and cellular response. The TH2 response was initially exacerbated and detected as increased allergen-specific IgE (sIgE) and IgG4 (sIgG4) levels and an increase in IL-4-producing cells, followed by downregulation of the TH2 response with a shift toward a TH1 cytokine profile. T cells with a regulatory phenotype were also elicited. Statistical correlations between immunologic measurements for each patient throughout therapy indicated that TH2 response downregulation and reduction of the immediate SLIT-induced IgE response were associated with increased allergen-specific IgG4 synthesis early in therapy. TH2 response downregulation by month 4 correlated with increased frequency of CD4(+) T cells with a regulatory phenotype by 12 months.

CONCLUSION
Changes in sIgE levels after therapy were linked to a specific IgG4 response, and production of blocking antibodies correlated with TH2 response downregulation. Reduced IL-4(+) cell frequency was linked to an increase in the frequency of CD4(+) T cells with a regulatory phenotype. Changes in sIgE levels and reduced IL-4 and blocking antibody levels could thus be used as indicators of a patient's immune response to therapy.

Suárez-Fueyo|Abel|A|
Ramos|Tania|T|
Galán|Agustín|A|
Jimeno|Lucia|L|
Wurtzen|Peter A|PA|
Marin|Alicia|A|
de Frutos|Consolación|C|
Blanco|Carlos|C|
Carrera|Ana C|AC|
Barber|Domingo|D|
Varona|Rosa|R|

Cytotoxic T lymphocyte–associated antigen 4

P P P P P P P P M U M U M U U M R U U U U


No evidence for race and socioeconomic status as independent predictors of 30-day readmission rates following orthopedic surgery.

Abstract: The Centers for Medicare & Medicaid Services considers readmissions within 30 days of discharge to be a quality indicator. Hospitals' and eventually physicians' readmission rates will be used to determine payment for services. It is imperative that health care providers understand which patients are at risk for readmission so that they can apply the appropriate preventive interventions. The research team analyzed all orthopedic admissions and readmissions at their institution from September 2008 to April 2011 in this study. Preparing for the next stage in health care reform, identifying any preoperative factors that may place certain patients into a "high-risk" category for readmission following an orthopedic procedure is of paramount importance. This data analysis of more than 13 000 patients noted that race-based and income-based risk factors did not translate into significant risk factors or predictors of 30-day readmission following orthopedic admission.

Hunter|Tracey|T|
Yoon|Richard S|RS|
Hutzler|Lorraine|L|
Band|Philip|P|
Liublinksa|Victoria|V|
Slover|James|J|
Bosco|Joseph A|JA|

D015331:Cohort Studies
D005260:Female
D054625:Healthcare Disparities
D006801:Humans
D007902:Length of Stay
D008297:Male
D008875:Middle Aged
D019637:Orthopedic Procedures
D010359:Patient Readmission
D011183:Postoperative Complications
D011379:Prognosis
D044469:Racial Groups
D012307:Risk Factors
D012923:Social Class
D062505:Value-Based Purchasing


An ancestry informative marker panel design for individual ancestry estimation of Hispanic population using whole exome sequencing data.

Abstract:
BACKGROUND
Europeans and American Indians were major genetic ancestry of Hispanics in the U.S. These ancestral groups have markedly different incidence rates and outcomes in many types of cancers. Therefore, the genetic admixture may cause biased genetic association study with cancer susceptibility variants specifically in Hispanics. For example, the incidence rate of liver cancer has been shown with substantial disparity between Hispanic, Asian and non-Hispanic white populations. Currently, ancestry informative marker (AIM) panels have been widely utilized with up to a few hundred ancestry-informative single nucleotide polymorphisms (SNPs) to infer ancestry admixture. Notably, current available AIMs are predominantly located in intron and intergenic regions, while the whole exome sequencing (WES) protocols commonly used in translational research and clinical practice do not cover these markers. Thus, it remains challenging to accurately determine a patient's admixture proportion without additional DNA testing.

RESULTS
In this study we designed an unique AIM panel that infers 3-way genetic admixture from three distinct and selective continental populations (African (AFR), European (EUR), and East Asian (EAS)) within evolutionarily conserved exonic regions. Initially, about 1 million exonic SNPs from selective three populations in the 1000 Genomes Project were trimmed by their linkage disequilibrium (LD), restricted to biallelic variants, and finally we optimized to an AIM panel with 250 SNP markers, or the UT-AIM250 panel, using their ancestral informativeness statistics. Comparing to published AIM panels, UT-AIM250 performed better accuracy when we tested with three ancestral populations (accuracy: 0.995 ± 0.012 for AFR, 0.997 ± 0.007 for EUR, and 0.994 ± 0.012 for EAS). We further demonstrated the performance of the UT-AIM250 panel to admixed American (AMR) samples of the 1000 Genomes Project and obtained similar results (AFR, 0.085 ± 0.098; EUR, 0.665 ± 0.182; and EAS, 0.250 ± 0.205) to previously published AIM panels (Phillips-AIM34: AFR, 0.096 ± 0.127, EUR, 0.575 ± 0.290, and EAS, 0.330 ± 0.315; Wei-AIM278: AFR, 0.070 ± 0.096, EUR, 0.537 ± 0.267, and EAS, 0.393 ± 0.300). Subsequently, we applied the UT-AIM250 panel to a clinical dataset of 26 self-reported Hispanic patients in South Texas with hepatocellular carcinoma (HCC). We estimated the admixture proportions using WES data of adjacent non-cancer liver tissues (AFR, 0.065 ± 0.043; EUR, 0.594 ± 0.150; and EAS, 0.341 ± 0.160). Similar admixture proportions were identified from corresponding tumor tissues. In addition, we estimated admixture proportions of The Cancer Genome Atlas (TCGA) collection of hepatocellular carcinoma (TCGA-LIHC) samples (376 patients) using the UT-AIM250 panel. The panel obtained consistent admixture proportions from tumor and matched normal tissues, identified 3 possible incorrectly reported race/ethnicity, and/or provided race/ethnicity determination if necessary.

CONCLUSIONS
Here we demonstrated the feasibility of using evolutionarily conserved exonic regions to infer admixture proportions and provided a robust and reliable control for sample collection or patient stratification for genetic analysis. R implementation of UT-AIM250 is available at https://github.com/chenlabgccri/UT-AIM250.

Wang|Li-Ju|LJ|
Zhang|Catherine W|CW|
Su|Sophia C|SC|
Chen|Hung-I H|HH|
Chiu|Yu-Chiao|YC|
Lai|Zhao|Z|
Bouamar|Hakim|H|
Ramirez|Amelie G|AG|
Cigarroa|Francisco G|FG|
Sun|Lu-Zhe|LZ|
Chen|Yidong|Y|

Hispanics population
Whole exome sequencing
Admixture
Ancestry Informative Markers (AIMs)
Hepatocellular carcinoma
STRUCTURE


Novel Genetic Dysregulations and Oxidative Damage in Fusarium graminearum Induced by Plant Defense Eliciting Psychrophilic Bacillus atrophaeus TS1.

Abstract: This study elaborates inter-kingdom signaling mechanisms, presenting a sustainable and eco-friendly approach to combat biotic as well as abiotic stress in wheat. Fusarium graminearum is a devastating pathogen causing head and seedling blight in wheat, leading to huge yield and economic losses. Psychrophilic Bacillus atrophaeus strain TS1 was found as a potential biocontrol agent for suppression of F. graminearum under low temperature by carrying out extensive biochemical and molecular studies in comparison with a temperate biocontrol model strain Bacillus amyloliquefaciens FZB42 at 15 and 25 °C. TS1 was able to produce hydrolytic extracellular enzymes as well as antimicrobial lipopeptides, i.e., surfactin, bacillomycin, and fengycin, efficiently at low temperatures. The Bacillus strain-induced oxidative cellular damage, ultrastructural deformities, and novel genetic dysregulations in the fungal pathogen as the bacterial treatment at low temperature were able to downregulate the expression of newly predicted novel fungal genes potentially belonging to necrosis inducing protein families (fgHCE and fgNPP1). The wheat pot experiments conducted at 15 and 25 °C revealed the potential of TS1 to elicit sudden induction of plant defense, namely, H2O2 and callose enhanced activity of plant defense-related enzymes and induced over-expression of defense-related genes which accumulatively lead to the suppression of F. graminearum and decreased diseased leaf area.

genetic dysregulations
psychrophilic
biochemical
necrosis inducing proteins
biotic/abiotic stresses
plant defense induction


Remission of Inflammatory Bowel Disease in Glucose-6-Phosphatase 3 Deficiency by Allogeneic Haematopoietic Stem Cell Transplantation.

Abstract: Mendelian disorders in glucose-6-phosphate metabolism can present with inflammatory bowel disease [IBD]. Using whole genome sequencing we identified a homozygous variant in the glucose-6-phosphatase G6PC3 gene [c.911dupC; p.Q305fs*82] in an adult patient with congenital neutropenia, lymphopenia and childhood-onset, therapy-refractory Crohn's disease. Because G6PC3 is expressed in several haematopoietic and non-haematopoietic cells it was unclear whether allogeneic stem cell transplantation [HSCT] would benefit this patient with intestinal inflammation. We show that HSCT resolves G6PC3-associated immunodeficiency and the Crohn's disease phenotype. It illustrates how even in adulthood, next-generation sequencing can have a significant impact on clinical practice and healthcare utilization in patients with immunodeficiency and monogenic IBD.

Bolton|Chrissy|C|
Burch|Nicola|N|
Morgan|James|J|
Harrison|Beth|B|
Pandey|Sumeet|S|
Pagnamenta|Alistair T|AT|
|||
Taylor|Jenny C|JC|
Taylor|John M|JM|
Marsh|Judith C W|JCW|
Potter|Victoria|V|
Travis|Simon|S|
Uhlig|Holm H|HH|

D000080984:Congenital Bone Marrow Failure Syndromes

D018380:Hematopoietic Stem Cell Transplantation

inflammatory bowel disease
genomics
immunodeficiency
Exome sequencing


The Protective Effect of Testosterone on the Ovarian Reserve During Cyclophosphamide Treatment.

Abstract:
Introduction
Cyclophosphamide, which is widely used to treat malignant disease, causes ovarian follicular atresia, which leads to premature ovarian insufficiency. The present study evaluated the protective effect of testosterone in preventing the decline in the ovarian reserve during cyclophosphamide treatment.

Methods
Using the COV434 human granulosa cell line, the protective effect of testosterone against cyclophosphamide was evaluated by immunocytochemistry, Western blotting and an MTS assay. The follicles in mouse ovaries and serum anti-Mullerian hormone were also assessed to evaluate the effects of testosterone.

Results
Testosterone suppressed the decrease in cell viability and apoptosis caused by cyclophosphamide treatment in vitro. In vivo, the number of atretic follicles in the mouse ovary was significantly lower in the testosterone plus cyclophosphamide group than in the cyclophosphamide alone group (p=0.03). The serum anti-Mullerian hormone was significantly higher in the testosterone plus cyclophosphamide group than in the cyclophosphamide alone group (16.2 [9.7-22.6]) vs 11.2 [8.9-12.1], p<0.01). The rate of cleaved Caspase-3 expression in the testosterone plus cyclophosphamide group was lower than that in the cyclophosphamide alone group (28.4% vs 48.6%, p=0.03).

Conclusion
These findings indicated that testosterone has the potential to prevent ovarian damage induced by cyclophosphamide by protecting granulosa cells from cyclophosphamide-induced apoptosis.

testosterone
cyclophosphamide
follicular atresia
granulosa cells
primary ovarian insufficiency


Phenolic acid and flavonoid-rich fraction of Sasa quelpaertensis Nakai leaves prevent alcohol induced fatty liver through AMPK activation.

Abstract:
ETHNOPHARMACOLOGICAL RELEVANCE
Sasa quelpaertensis Nakai is an edible dwarf bamboo cultivated mainly in Jeju Island, South Korea and its leaf displays various health-promoting properties including antioxidant scavenging.

AIM OF THE STUDY
In this study, we aimed at elucidating its hepatoprotective effect against alcohol-induced fatty liver.

METHODS
In in vitro study, we evaluated the cytotoxicity and hepatoprotective effect of different solvent fractions (aqua, butanol, chloroform, ethyl acetate and hexane) of 80% EtOH extract of S. quelpaertensis Nakai leaf. In vivo experiment performed using binge alcohol consumption model.

RESULTS
Although all five fractions (0-1000 µg/mL) were non-cytotoxic to HepG2 cells, only ethyl acetate fraction (SQEA), rich in phenolic acids such as p-coumaric acid and flavonoids particularly myristin, showed hepatoprotective effect against EtOH (400 mM) in HepG2 cells. Furthermore, SQEA significantly decreased the ethanol induced cell death and enhanced the cell proliferation. In in vivo experiment using binge consumption model (5 g of EtOH/kg body weight in every 12 h for 3 times), SQEA treatment (10, 50 and 100 mg/kg) markedly reduced the alcohol induced histopathological changes and serum EtOH content, and reversed the reduction of glutathione level in ethanol challenged livers. Further, it suppressed the expression of cytochrome P450 2E1 (CYP2E1). In particular, SQEA activated AMP activated protein kinase (AMPK) pathway, and decreased the expression of tumor necrosis factor receptor-1 (TNFR1), which attenuated lipogenesis via decreased expression of fatty acid synthase (FAS). Inhibited lipogenesis due to SQEA treatment directed towards decreased perilipin-2 expression. These results indicate that SQEA has hypolipidemic effect which is mediated by decreased oxidative stress, increased fatty acid oxidation response and decreased lipogenesis.

CONCLUSION
Our results suggest the possibility of developing SQEA as a natural hepatoprotective agent potent in attenuating alcohol-induced fatty liver.

Madushani Herath|Kalahe Hewage Iresha Nadeeka|KHIN|

D017392:Thiobarbituric Acid Reactive Substances

Alcohol
Fatty liver
HepG2 cells
Fatty acid
Hepatotoxic


Treatment outcomes of curative radiotherapy in patients with vulvar cancer: results of the retrospective KROG 1203 study.

Abstract:
PURPOSE
We evaluated the prognostic factors and clinical outcomes of 56 patients with vulvar cancer treated with curative radiotherapy (RT) or concurrent chemoradiotherapy.

MATERIALS AND METHODS
Overall survival (OS) and disease-free survival (DFS) were assessed retrospectively. Prognostic factors evaluated included age, International Federation of Gynecology and Obstetrics (FIGO) stage, TNM classification, tumor size, treatment modality, RT duration, and RT field. The association between the tumor human papillomavirus (HPV) status and survival was analyzed in 35 patients.

RESULTS
During the median follow-up of 2.8 years (range, 0.3 to 18.9 years), 21 patients (37.5%) experienced treatment failure. Fifteen patients (27%) had local failure: nine (16%) local failure only, three (5%) locoregional failure, two (4%) local and distant failure, and one (2%) locoregional and distant failure. Of 56 patients, seven (13%) had persistent disease at the first follow-up at 2 months and all but one died within a year after completing RT. The 5-year OS and DFS were 51.6% and 44.0%, respectively. In multivariate analysis, clinical size ≥3 cm predicted a poor prognostic factor for DFS (p = 0.040) and age (≥70 years) was poor prognostic for DFS (p = 0.032) and OS (p = 0.048). Patients with HPV-positive tumors tended to have better 5-year OS and DFS, but the differences were not significant statistically.

CONCLUSION
Clinical size ≥3 cm was a significant prognostic factor for DFS. However, age was the most important prognostic factor for DFS and OS in patients treated with curative RT. Further studies are needed to determine which treatment should be considered for old age ≥70 years.

Kim|Youngkyong|Y|
Kim|Joo-Young|JY|
Kim|Ja Young|JY|
Lee|Nam Kwon|NK|
Kim|Jin Hee|JH|
Kim|Yong Bae|YB|
Kim|Young Seok|YS|
Kim|Juree|J|
Kim|Yeon-Sil|YS|
Yang|Dae Sik|DS|
Kim|Yeon-Joo|YJ|

Radiotherapy
Vulvar cancer
Survival
Risk factor


Quantitative Risk Assessment Model for Salmonellosis in Chicken Skewers from Street Food Vendors in South Korea.

Abstract: Extended holding time increases likelihood of illness in warmer than it does in cooler months. Split heating is less effective than continuous heating for inactivation of microbes. Longer holding times make meat more vulnerable to microbes.

Chicken
Street food vendor
Monte Carlo simulation
Predictive microbiology
Quantitative microbial risk assessment


A cross-sectional analysis of trust of information and COVID-19 preventative practices among people with disabilities.

Abstract:
BACKGROUND
Trust of information shapes adherence to recommended practices and speed of public compliance during public health crises. This is particularly important for groups with higher rates of high-risk health conditions, including those aged 65 and over and people with disabilities.

OBJECTIVE
We examined trust in information sources and associated adherence to COVID-19 public health recommendations among people with disabilities living in metropolitan, micropolitan, and noncore counties.

METHODS
We recruited participants using Amazon's Mechanical Turk (MTurk) and screened for disability status (n = 408). We compared sociodemographic groups with t-tests, Pearson's correlations, and Chi-square, as appropriate. We used linear regression to examine factors associated with trust in information and compliance with CDC recommended COVID-19 practices.

RESULTS
Nonmetro respondents had the lowest trust ratings among all demographic groups, and reported significantly less trust in most information sources. Respondents aged 65 and over reported the highest compliance with CDC recommended practices, while those from nonmetro areas reported the lowest. A regression model for adherence to CDC recommended practices was significant (F = 11.87, P ≤ .001), and explained 33% of the variance. Specifically, increased adherence was associated with being over 65, female, and higher general trust scores. Decreased practices were associated with being nonwhite, nonmetro, higher trust scores in President Trump, and having a communication disability.

CONCLUSIONS
Trust in information sources is associated with action. It is important to provide clear, consistent, and non-polarizing messages during public health emergencies to promote widespread community action.

Trust
COVID-19
Disability
Public health
Rural


Ecological effects of sex differ with trophic positions in a simple food web.

Abstract: Sexual differences in parental investment, predation pressure, and foraging efforts are common in nature and affect the trophic flow in food webs. Specifically, the sexual differences in predator and prey behavior change in trophic inflow and outflow, respectively, while those in parental investment alter the reproductive allocation of acquired resources in the population. Consequently, these factors may play an important role in determining the system structure and persistence. However, few studies have examined how sexual differences in trophic flow affect food web dynamics. In this study, I show the ecological role of sex by explicitly incorporating sexual differences in trophic flow into a three-species food web model. The results demonstrated that the ecological waste of males, that is, the amount of trophic inflow into males with less parental investment, plays an important role in system persistence and structure. In particular, the synergy between sexual differences in parental investment and trophic inflows and outflows is important in determining web persistence: Significant impacts of male-biased trophic flows require the condition of anisogamy. In addition, the dynamic effects of the ecological waste of males differ with trophic level: The coexistence of a food web occurs more frequently with biased inflows into predator males, but occurs less frequently with biased inflows into consumer males. The model analysis indicates that investigating the pattern of sexual differences among trophic positions can enrich our understanding of food web persistence and structure in the real world.

sexual difference
trophic flow
persistence
anisogamy
omnivory
predator–prey interaction


Mapping Brazilian spotted fever: Linking etiological agent, vectors, and hosts.

Abstract: Brazilian spotted fever (BSF) is a highly lethal disease in southeastern Brazil. BSF is caused by the bacterium Rickettsia rickettsii and is transmitted by the bites of the tick of the genus Amblyomma. The spatial distribution of BSF risk areas is not well known in the country given the complexity of the transmission cycle. This study used the ecological niche modeling (ENM) approach to anticipate the potential distribution of the etiological agent (Rickettsia rickettsii), vectors (Amblyomma sculptum and A. dubitatum), and hosts (Hydrochoerus hydrochaeris, Didelphis aurita, and D. marsupialis) of BSF in Brazil. We compiled occurrence records for all vectors, hosts, and BSF from our own field surveillance, online repositories, and literature. ENM identified BSF risk areas in southeastern and southern Brazil, and anticipated other dispersed suitable areas in the western, central, and northeastern coast regions of Brazil. Tick vectors and mammalian hosts were confined to these same areas; however, host species showed broader suitability in northern Brazil. All species ENMs performed significantly better than random expectations. We also tested the BSF prediction based on 253 additional independent cases identified in our surveillance; the model anticipated 251 out of 253 of these independent cases. Background similarity tests comparing the ENMs of R. rickettsii, tick vectors, and mammalian hosts were unable to reject null hypotheses of niche similarity. Finally, we observed close coincidence between independent BSF cases, and areas suitable for combinations of vectors and hosts, reflecting the ability of these model pairs to anticipate the distribution of BSF cases across Brazil.

Donalisio|Maria Rita|MR|
Souza|Celso E|CE|
Angerami|Rodrigo N|RN|
Samy|Abdallah M|AM|

Brazilian spotted fever
Brazil
Amblyomma sculptum
Hydrochoerus hydrochaeris
Didelphis aurita
Niche similarity
Amblyomma dubitatum
Didelphis marsupialis
Niche overlap
Tick vectors, Rickettsia rickettsii


Comparing the risk of hepatitis B virus reactivation between direct-acting antiviral therapies and interferon-based therapies for hepatitis C.

Abstract: Hepatitis B virus (HBV) reactivation has been reported during antihepatitis C treatment in patients with hepatitis C virus (HCV) and HBV co-infection. We aimed to evaluate the frequency and risk factors of HBV reactivation during anti-HCV therapy and compared those between interferon (IFN)-free direct-acting antiviral (DAA) therapies and IFN-based therapies. Three hundred and twenty-two patients with HCV infection receiving anti-HCV therapy were retrospectively screened. The baseline HBV infection statuses of all eligible patients and the HBV-DNA level of all patients with current or previous HBV infection were examined at the end of treatment. In patients with baseline anti-HBs positivity, changes in anti-HBs titre were evaluated. Of 287 patients who met the inclusion criteria, 157 had current (n=4) or previous (n=153) HBV infection; 85 were treated with IFN-free DAA therapies and 72 were treated with IFN-based therapies. Six patients experienced HBV reactivation (n=2) or HBV reappearance (n=4) after IFN-free DAA therapies, while no patient developed HBV reactivation after IFN-based therapies. The risk factors of HBV reactivation or reappearance were DAA therapies and a reduction in anti-HBs titre to <12 mIU mL-1 by the end of treatment. The decline changes of anti-HBs titre were significantly higher in patients treated with DAA therapies. Although HBV reactivation hepatitis was not observed, three of four patients with HBV reactivation or reappearance after achieving HCV eradication had viremia 8 weeks after completion of therapy. A significant proportion of patients develop HBV reactivation or reappearance without hepatitis after IFN-free DAA therapies. Low levels of anti-HBs and their decrease to <12 mIU mL-1 after treatment are significant risk factors for HBV reactivation or reappearance.

Kawagishi|N|N|0000-0002-2953-6242 Suda|G|G| Onozawa|M|M| Kimura|M|M| Maehara|O|O| Ohara|M|M| Izumi|T|T| Umemura|M|M| Ito|J|J| Nakai|M|M| Sho|T|T| Natsuizaka|M|M| Morikawa|K|K| Ogawa|K|K| Sakamoto|N|N|

hepatitis B virus
reactivation
direct-acting antivirals
hepatitis C virus
interferon
de novo reactivation


Haploidy in Humans: An Evolutionary and Developmental Perspective.

Abstract: Although haploidy has not been observed in vertebrates, its natural occurrence in various eukaryotic species that had diverged from diploid ancestors suggests that there is an innate capacity for an organism to regain haploidy and that haploidy may confer evolutionary benefits. Haploid embryonic stem cells have been experimentally generated from mouse, rat, monkey, and humans. Haploidy results in major differences in cell size and gene expression levels while also affecting parental imprinting, X chromosome inactivation, and mitochondrial metabolism genes. We discuss here haploidy in evolution and the barriers to haploidy, in particular in the human context.

Human
Diploidization
Haploid
Embryonic stem cells
X chromosome inactivation
Evolution
Differentiation
Genomic imprinting
Ploidy
Pluripotent stem cells


Cognitive Behavioral-Active Music Pastoral Therapy for Millennials' Academic Anxiety: How & Why?

Abstract: This study used quasi-experimental design with repeated measures (pre-test, post-test, and follow-up). Based on the post-test and the follow-up comparison, active music therapy was effective in reducing academic anxiety after two weeks of the treatment. Active music therapy which are integrated in CBT group counseling not only can overcome individual problems, but the therapies can also help individuals analyze their own thoughts and behavior.

millennials
academic anxiety
music therapy
Cognitive behavioral therapy
pastoral care
pastoral counseling


Overexpression of activating transcription factor 3 exerts suppressive effects in HepG2 cells.

Abstract: The present study observed and compared the biological behaviour of HepG2 cells prior and subsequent to the overexpression of activating transcription factor 3 (ATF3). Experiments investigating the cytological function by which ATF3 affects liver cancer cells were also performed. MTT, Transwell and flow cytometry assays were used to observe and detect the biological behaviour of HepG2 cells with and without lentivirus (LV)‑ATF3‑enhanced green fluorescent protein (EGFP) infection. The effects of ATF3 overexpression on cell proliferation, migration, apoptosis and cell cycle progression were evaluated. The LV‑ATF3‑EGFP overexpression vector was successfully constructed, and the HepG2 cells were successfully infected with the vector. Following ATF3 overexpression, cell proliferation was decreased, the rate of cell apoptosis was accelerated and cell cycle progression was slowed (P<0.05). There were no marked changes in cell migration (P>0.05), although there was a trend towards a gradual decrease. In conclusion, ATF3 exerted suppressive effects in HepG2 cells, potentially by inhibiting cancer cell growth, accelerating cell apoptosis, and blocking cell cycle progression. Intervention targeting ATF3 expression may represent a novel approach for the prevention and treatment of human liver cancer.

Li|Xiaoyan|X| Zang|Shengbing|S| Cheng|Haili|H| Li|Jiasi|J| Huang|Aimin|A|

D051700:Activating Transcription Factor 3

D015972:Gene Expression Regulation, Neoplastic

activating  transcription  factor  3
lentiviral  vectors  of  overexpression
cytological mechanism


Highest and Fastest Removal Rate of PbII Ions through Rational Functionalized Decoration of a Metal-Organic Framework Cavity.

Abstract: To overcome the challenge of developing a multipurpose adsorbent for effective removal of toxic and carcinogenic PbII ions from aqueous solutions, a made-for-purpose functional group (N1 ,N2 -di(pyridine-4-yl)oxalamide) was rationally designed and incorporated into the cavities of a Zn metal-organic framework (MOF), namely, TMU-56. Large enough pore size along with high densities of strong metal chelating sites lead not only to the highest uptake capacity for PbII ions, but also the fastest removal rate that has ever been reported for functionalized MOFs, occurring in just 20 s. Moreover, high concentrations of lead ions favor the ion exchange reaction, resulting in a high degree of metal exchange. In addition, TMU-56 can be a practical adsorbent because of its notable performance in the simultaneous removal of several toxic and carcinogenic heavy metals from wastewater, which has rare precedence.

PbII ions
metal-organic frameworks
wastewater
adsorption


Traditional Chinese Medicine Formula Kang Shuai Lao Pian Improves Obesity, Gut Dysbiosis, and Fecal Metabolic Disorders in High-Fat Diet-Fed Mice.

Abstract: High-fat diet (HFD)-induced obesity is a risk factor for many metabolic disorders including cardiovascular diseases, diabetes, and fatty liver disease. Although there are accumulating evidences supporting the assumption that regulating gut microbiota as well as its metabolic status is able to mitigate obesity, the inner relationship between the obesity-related gut microbiota and the relevant metabolites are not well defined. In current study, we applied a traditional herbal formula Kang Shuai Lao Pian (KSLP) to HFD-fed mice and evaluated its effect against obesity. Emphases were addressed on identifying profiles of gut microbiota and fecal metabolites with the aid of 16S rRNA gene sequencing and non-target fecal metabolomics techniques. We showed that KSLP could improve HFD-induced obesity, glucose tolerance disorder, as well as gut dysbiosis. In the gut, KSLP corrected the increased abundance of Firmicutes and Proteobacteria, increased ratio of Firmicutes/Bacteroidetes, and decreased abundance of Bacteroidetes caused by HFD. KSLP also reversed HFD-induced significant changes in the abundance of certain genus including Intestinimonas, Oscillibacter, Christensenellaceae_R-7_group, Ruminococcaceae_UCG-010, and Aliihoeflea. Pearson correlation analysis indicated that except for Ruminococcaceae_UCG-010, other four genera had positive correlations with obesity. In addition, 22 key fecal metabolites responding to KSLP treatment were identified. Pearson correlation analysis showed that those metabolites are intimately related to KSLP effective genera of Intestinimonas, Oscillibacter, and Christensenellaceae_R-7_group. Our results indicate that KSLP is a promising traditional Chinese medicine (TCM) applicable for individuals with HFD habit. Intestinimonas, Oscillibacter, and Christensenellaceae_R-7_group might be responsible for the regulatory effect of KSLP. Linking of obesity phenotypes with gut microbiota as well as fecal metabolites is therefore a powerful research strategy to reveal the mechanism of obesity and the targets of intervention.

Gong|Shuqing|S| Ye|Tingting|T| Wang|Meixia|M| Wang|Mengying|M| Li|Yufei|Y| Ma|Lina|L| Yang|Yulian|Y| Wang|Yi|Y| Zhao|Xiaoping|X| Liu|Li|L| Yang|Min|M| Chen|Huan|H| Qian|Jing|J|

Traditional Chinese medicine
obesity
high-fat diet
gut microbiota
correlation analysis
fecal non-targeted metabolomics


The Interpersonal Sunk-Cost Effect.

Abstract: The sunk-cost fallacy-pursuing an inferior alternative merely because we have previously invested significant, but nonrecoverable, resources in it-represents a striking violation of rational decision making. Whereas theoretical accounts and empirical examinations of the sunk-cost effect have generally been based on the assumption that it is a purely intrapersonal phenomenon (i.e., solely driven by one's own past investments), the present research demonstrates that it is also an interpersonal effect (i.e., people will alter their choices in response to other people's past investments). Across eight experiments ( N = 6,076) covering diverse scenarios, I documented sunk-cost effects when the costs are borne by someone other than the decision maker. Moreover, the interpersonal sunk-cost effect is not moderated by social closeness or whether other people observe their sunk costs being "honored." These findings uncover a previously undocumented bias, reveal that the sunk-cost effect is a much broader phenomenon than previously thought, and pose interesting challenges for existing accounts of this fascinating human tendency.

decision making
heuristics
open data
open materials
preferences
preregistered
social influence


Reconstruction of the Anterior Acetabular Wall to Repair Symptomatic Defects Consecutive to Cup Malpositioning at Total Hip Arthroplasty.

Abstract: Iliopsoas impingement (IPI) causes persistent groin pain and functional impairment after total hip arthroplasty (THA). It is caused most often by an overhang of the cup. Psoas tenotomy may successfully treat IPI in overhangs <8 mm. Cup revision usually is recommended for larger overhangs. Muscle sparing reconstruction of the anterior acetabular wall may be an alternative when malposition of the cup at THA caused a bony defect that would persist after simple cup revision. The surgical technique and results from one patient are presented. The patient rapidly became asymptomatic and remained pain free at 2-year follow-up. Any bone substance defect of the acetabulum should be considered when evaluating treatment options for IPI after THA.

Pozzi|Lara|L| Lehnen|Aude|A| Kalberer|Fabian|F| Meier|Christoph|C| Wahl|Peter|P|

Total hip arthroplasty
Iliopsoas impingement
Psoas tenotomy
Acetabular reconstruction
Minimally invasive


Challenges related to migration and child attachment: A pilot study with South Asian immigrant mother-child dyads.

Abstract: This pilot study examined psychological, social and cultural risk factors for child insecure attachment in a sample of South Asian immigrant families experiencing high migration stress in Montreal, Canada. Thirty-three participants were recruited through a local Health and Social Service organization. Maternal anxiety and depression, social support, and national and religious sense of belonging were assessed. Child attachment behaviors were coded from a 15 min free play period. Results indicated that maternal depressive symptoms were related to lower child attachment security scores. Lower support from friends was related to greater child ambivalent attachment behaviors. A higher sense of belonging to the country of origin was related to greater child disorganized attachment behaviors. These findings suggest that migration stresses, which include maternal depression, lack of social support and the sense of belonging, are associated with child attachment, and these variables should be considered in the design of appropriate interventions.

attachment
immigration
social support
sense of belonging
Maternal mental health


Sustained release timolol maleate loaded ocusert based on biopolymer composite.

Abstract: In the present investigation, the effect of timolol maleate loaded ocuserts was studied as an alternative for conventional anti-glaucoma formulation. Ocuserts were prepared using natural polymer sodium alginate and ethyl cellulose. Physico-chemical properties along with drug entrapment efficiency (94-98%), content uniformity (93.1% ± 0.264-98.00% ± 0.321), in vitro drug release (83.42% ± 0.35 at end of 12 h), ex vivo permeation all showed satisfactory results, which was found to follow zero order kinetics. Ex vivo permeation studies showed better results, revealed that the permeability coefficient was dependent on polymer type. The sterility test accelerated stability studies and in vivo studies such as eye irritancy test, in vivo drug release of the optimized ocusert was determined. The anti-glaucoma activity was measured using Schiotz tonometer at different time interval. Significant reduction in Intra ocular pressure (IOP) within 3 days was observed in case of rabbits treated with ocusert in comparison to the rabbit treated with marketed eye drop formulation. Hence timolol maleate loaded ocuserts proved to be a promising and viable alternative over conventional eye formulation for the sustained and controlled ophthalmic drug delivery, targeting the drug within the ocular globe thus improving patient compliance for the treatment of glaucoma.

Nair|Revathy V|RV|
S|Shefrin|S|
Suresh|Akhil|A|
K R|Anoop|A|
Nair|Sreeja C|SC|

Timolol maleate
Sodium alginate
Sustained release ocuserts


Cryoanalgesia for postsurgical pain relief in adults: A systematic review and meta-analysis.

Abstract:
Background
Despite advances in pain management, postoperative pain continues to be an important problem with significant burden. Many current therapies have dose-limiting adverse effects and are limited by their short duration of action. This review examines the evidence for the efficacy and safety of cryoanalgesia in postoperative pain.

Materials and methods
This review was registered in PROSPERO and prepared in accordance with PRISMA. MEDLINE, EMBASE, and Cochrane databases were searched until July 2020. We included randomized controlled trials (RCTs) of adults evaluating perioperatively administered cryoanalgesia for postoperative pain relief.

Results
Twenty-four RCTS were included. Twenty studies examined cryoanalgesia for thoracotomy, two for herniorrhaphy, one for nephrectomy and one for tonsillectomy. Meta-analysis was performed for thoracic studies. We found that cryoanalgesia with opioids was more efficacious than opioid analgesia alone for acute pain (mean difference [MD] 2.32 units, 95 % confidence interval [CI] -3.35 to -1.30) and persistent pain (MD 0.81 units, 95 % CI -1.10 to -0.53) after thoracotomy. Cryoanalgesia with opioids also resulted in less postoperative nausea compared to opioid analgesia alone (relative risk [RR] 0.23, 95 % CI 0.06 to 0.95), but there was no difference in atelectasis (RR 0.38, 95 % CI 0.07 to 2.17).

Conclusion
Heterogeneity in comparators and outcomes were important limitations. In general, reporting of adverse events was incomplete and inconsistent. Many studies were over two decades old, and most were limited in how they described their methodology. Considering the potential, larger RCTs should be performed to better understand the role of cryoanalgesia in postoperative pain management.

Park|Rex|R| Coomber|Michael|M| Gilron|Ian|I| Shanthanna|Harsha|H|

Cryoanalgesia
Pain
Systematic review
Postoperative pain


Retinal electrophysiological changes related to early versus late silicone oil removal.

Abstract:
PURPOSE
To compare between the effect of early (3 months) and late (6 months) silicone removal on the electroretinogram records.

METHODS
Thirty-four eyes with complex primary rhegmatogenous macula off retinal detachment undergone vitrectomy. Silicone oil was removed after 3 months in group I and after 6 months in group II. Scotopic and photopic ERGs, pattern electroretinogram (PERG) and multifocal ERG (mfERG) and best-corrected visual acuity (BCVA) were recorded for all eyes RESULTS: Preoperative mean best corrected visual acuity (BCVA) measured was 0.93 ± 0.05 in group I and 0.9 ± 0.08 in group II. One month after silicone removal, mean BCVA was 0.20 ± 0.04 and 0.18 ± 0.02 in groups I and II respectively. Before silicone oil removal the electroretinographic a- and b-waves were greatly reduced in both groups with no significant difference between them. One month after removal of silicone oil, the electroretinographic a- and b-waves increased in both groups with no significant difference between the two groups (p = 0.46 and 0.23 respectively).

CONCLUSION
The amplitudes of the ERGs increase after removal of silicone oil tamponade with no difference between early (3 months) and late (6 months) removal.

D005500:Follow-Up Studies
D006801:Humans
D012163:Retinal Detachment
D012827:Silicone Oils
D014792:Visual Acuity
D014821:Vitrectomy

Silicone oil
Electroretinogram
Scotopic response
Vitrectomy photopic response


A Systematic Analysis of Treatment Effects on Depressive Symptom Severity by Level of Coercion.

Abstract: Few studies examine the effect of interpersonal, regulatory or legal coercion on the treatment of depressive symptoms. This retrospective case-control study compared the recovery rates of 574 adults whose level of coercion was scored on a 0-3 scale from fully voluntary to severe coercion when admitted to the Menninger Clinic between 2009 and 2014. The change in Patient Health Questionnaire-9 (PHQ-9) scores (measuring depression severity) from admission to discharge served as the primary outcome measure. Level of coercion was not associated with a difference in rate of improvement in PHQ-9 score. Greater improvement in PHQ-9 scores was associated with (a) older age, (b) lack of a psychotic spectrum disorder diagnosis, (c) stronger working alliance with treatment team, and (d) less difficulty with emotional regulation [lower Difficulties in Emotion Regulation Scale (DERS) scores]. DERS scores were the most impactful factor. This study suggests that licensure boards can continue to mandate treatment despite concerns that coercion may decrease treatment effectiveness.

Scott Johnson|R|R|
Christopher Fowler|J|J|
Jani|Suni N|SN|
Eichelberger|Hillary L|HL|
Oldham|John M|JM|
Poa|Edward|E|
Graham|David P|DP|

Depression
Coercion
PHQ-9
Fitness for duty


Relation between left ventricular outflow tract obstruction and left ventricular shape in patients with hypertrophic cardiomyopathy: a cardiac magnetic resonance imaging study.

Abstract:
BACKGROUND
Hypertrophic cardiomyopathies (HCM) are often associated with left ventricular (LV) outflow tract obstruction, which can explain symptoms and impact prognosis.

AIMS
To better understand the mechanisms that link obstruction and LV shape in HCM.

METHODS
Patients with HCM who underwent cardiac magnetic resonance (CMR) imaging were included retrospectively. Obstructive HCM was defined as LV outflow gradient more than 30 mm Hg at rest by transthoracic echocardiography. The LV shape and mitral angle were assessed by CMR. Results were compared with control subjects.

RESULTS
Mean LV-mitral angle was smaller in patients with obstructive HCM (n=29) than in patients with non-obstructive HCM (n=15) or control subjects (n=15) (80 ± 5° vs 87 ± 7° [P=0.0002] and 89 ± 2° [P<0.0001]). Mean mitral papillary muscles angle was greater in patients with non-obstructive HCM than in patients with obstructive HCM or control subjects (136 ± 17° vs 123 ± 16° [P=0.007] and 118 ± 10° [P=0.002]). Patients with non-obstructive HCM had a greater mean LV-aortic root angle than patients with obstructive HCM or control subjects (139 ± 6° vs 135 ± 7° [P=0.04] and 133 ± 7° [P=0.03]).

CONCLUSION
There is a relation between morphological and functional parameters in HCM within which the mitral valve is probably part of pathophysiogenesis.

Martin|Romain|R| Lairez|Olivier|O| Boudou|Nicolas|N| Méjean|Simon|S| Lhermusier|Thibault|T| Dumonteil|Nicolas|N| Berry|Matthieu|M| Cognet|Thomas|T| Massabuau|Pierre|P| Elbaz|Meyer|M| Rousseau|Hervé|H| Galinier|Michel|M| Carrié|Didier|D|

D019028:Magnetic Resonance Imaging, Cine

Left ventricular outflow tract obstruction

Imagerie par résonance magnétique cardiaque

P P P P P P P P P P P P M U U U U U U M U P M M U


Insulin regulation of gluconeogenesis.

Abstract: The coordinated regulation between cellular glucose uptake and endogenous glucose production is indispensable for the maintenance of constant blood glucose concentrations. The liver contributes significantly to this process by altering the levels of hepatic glucose release, through controlling the processes of de novo glucose production (gluconeogenesis) and glycogen breakdown (glycogenolysis). Various nutritional and hormonal stimuli signal to alter hepatic gluconeogenic flux, and suppression of this metabolic pathway during the postprandial state can, to a significant extent, be attributed to insulin. Here, we review some of the molecular mechanisms through which insulin modulates hepatic gluconeogenesis, thus controlling glucose production by the liver to ultimately maintain normoglycemia. Various signaling pathways governed by insulin converge at the level of transcriptional regulation of the key hepatic gluconeogenic genes PCK1 and G6PC, highlighting this as one of the focal mechanisms through which gluconeogenesis is modulated. In individuals with compromised insulin signaling, such as insulin resistance in type 2 diabetes, insulin fails to suppress hepatic gluconeogenesis, even in the fed state; hence, an insight into these insulin-moderated pathways is critical for therapeutic purposes.

Hatting|Maximilian|M|
Tavares|Clint D J|CDJ|
Sharabi|Kfir|K|
Rines|Amy K|AK|
Puigserver|Pere|P|

insulin regulation gluconeogenesis glucose glycogenolysis


Immediate effect of photobiomodulation therapy on Achilles tendon morphology and mechanical properties: an exploratory study.

Abstract:
Objectives
Evaluate the immediate (within 4 hours) effects of laser-induced photobiomodulation (PBM) therapy on Achilles tendon morphology and mechanical properties in healthy and pathologic tendons.

Materials and Methods
Twenty people with healthy Achilles tendons and twelve people with Achilles tendinopathy participated. One Achilles tendon received PBM treatment following an established protocol and the contralateral side received a placebo treatment. Achilles tendon morphology and mechanical properties were evaluated bilaterally with ultrasound imaging and continuous shear wave elastography immediately before treatment, immediately after treatment, then 2- and 4-hours after treatment.

Results
There were no immediate effects of PBM on tendon morphology or mechanical properties when comparing the PBM-treated side and placebo-treated side within each cohort. Additionally, the effects of PBM did not differ between healthy and pathologic Achilles tendons.

Conclusion
When treated with a laser-induced PBM treatment, healthy and pathologic Achilles tendons do not have immediate (within 4 hours) changes in tendon morphology or mechanical properties. These findings suggest that PBM therapy can be administered before other clinical treatments or high-load activities.

Corrigan|Patrick|P|0000-0001-7263-5599
Cortes|Daniel H|DH|
Silbernagel|Karin Grävare|KG|

Tendinopathy
Ultrasound
Elastography
Laser Therapy
Material Properties
Tendinitis


Outcomes in Newly Diagnosed Atrial Fibrillation and History of Acute Coronary Syndromes: Insights from GARFIELD-AF.

Abstract:
BACKGROUND
Many patients with atrial fibrillation have concomitant coronary artery disease with or without acute coronary syndromes and are in need of additional antithrombotic therapy. There are few data on the long-term clinical outcome of atrial fibrillation patients with a history of acute coronary syndrome. This is a 2-year study of atrial fibrillation patients with or without a history of acute coronary syndromes.

METHODS
Adults with newly diagnosed atrial fibrillation and ≥1 investigator-defined stroke risk factor were enrolled in GARFIELD-AF between March 2010 and September 2015. The association between prior acute coronary syndromes and long-term outcomes was determined using a Cox proportional hazards model, adjusting for baseline risk factors, oral anticoagulation (OAC) ± antiplatelet (AP) therapy, and usual care.

RESULTS
Of 39,679 patients, 10.5% had a history of acute coronary syndromes. At 2-year follow-up, patients with prior acute coronary syndromes had higher adjusted risks of stroke/systemic embolism (hazard ratio [HR] 1.39; 95% confidence interval [CI], 1.08-1.78), major bleeding (HR 1.30; 95% CI, 0.95 -1.79), all-cause mortality (HR 1.34; 95% CI, 1.21 -1.49), cardiovascular mortality (HR 1.85; 95% CI, 1.51-2.26), and new acute coronary syndromes (HR 3.42; 95% CI, 2.62-4.45). Comparing antithrombotic therapy in the acute coronary syndromes vs no acute coronary syndromes groups, most patients received OAC ± AP: 60.8% vs 66.1%, but AP therapy was more likely in the acute coronary syndromes group (68.1% vs 32.9%), either alone (34.9% vs 20.8%) or with OAC (33.2% vs 12.1%). Overall, 17.8% in the acute coronary syndromes group received dual AP therapy with (5.3%) or without OAC (12.5%). Among patients with moderate/high risk for stroke/systemic embolism, fewer in the acute coronary syndromes group received OAC with or without AP therapy (Congestive heart failure, Hypertension, Age 75 years, Diabetes mellitus, prior Stroke, TIA, or thromboembolism, Vascular disease, Age 65-74 years, Sex category [CHA2DS2-VASc] 2: 52.1% vs 64.6%; CHA2DS2-VASc ≥3: 62.0% vs 70.7%), and the majority with a Hypertension (uncontrolled systolic blood pressure >160 mm Hg), Abnormal renal or liver function, previous Stroke, Bleeding history or predisposition, Labile international normalized ratios, Elderly, and concomitant Drugs or alcohol excess (HAS-BLED) score ≥3 were on AP therapy (83.8% vs 65.5%).

CONCLUSIONS
In GARFIELD-AF, previous acute coronary syndromes are associated with worse 2-year outcomes and a greater likelihood of under-treatment with OAC, while two-thirds of patients receive AP therapy. Major bleeding was more common with previous acute coronary syndromes, even after adjusting for all risk factors.

Verheugt|Freek W A|FWA|
Ambrosio|Giuseppe|G|
Atar|Dan|D|
Bassand|Jean-Pierre|JP|
Camm|A John|AJ|
Costabel|Juan Pablo|JP|
Fitzmaurice|David A|DA|
Illingworth|Laura|L|
Goldhaber|Samuel Z|SZ|
Goto|Shinya|S|
Haas|Sylvia|S|
Jansky|Petr|P|
Kayani|Gloria|G|
Stepinska|Janina|J|
Turpie|Alexander G G|AGG|
van Eickels|Martin|M|
Kakkar|Ajay K|AK|
|||

Stroke
Anticoagulation
Bleeding
Mortality
Antiplatelet therapy


Genetic diversity of Trichomonas vaginalis clinical isolates from Henan province in central China.

Abstract: Trichomonas vaginalis is a flagellated protozoan parasite that infects the human urogenital tract, causing the most common non-viral, sexually transmitted disease worldwide. In this study, genetic variants of T. vaginalis were identified in Henan Province, China. Fragments of the small subunit of nuclear ribosomal RNA (18S rRNA) were amplified from 32 T. vaginalis isolates obtained from seven regions of Henan Province. Overall, 18 haplotypes were determined from the 18S rRNA sequences. Each sampled population and the total population displayed high haplotype diversity (Hd), accompanied by very low nucleotide diversity (Pi). In these molecular genetic variants, 91.58% genetic variation was derived from intra-regions. Phylogenetic analysis revealed no correlation between phylogeny and geographic distribution. Demographic analysis supported population expansion of T. vaginalis isolates from central China. Our findings showing moderate-to-high genetic variations in the 32 isolates of T. vaginalis provide useful knowledge for monitoring changes in parasite populations for the development of future control strategies.

D000328:Adult
D002681:China
D016000:Cluster Analysis
D016054:DNA, Protozoan
D004275:DNA, Ribosomal
D005260:Female
D014644:Genetic Variation
D006801:Humans
D010802:Phylogeny
D016133:Polymerase Chain Reaction
D012337:RNA, Ribosomal, 18S
D017422:Sequence Analysis, DNA
D014245:Trichomonas Infections
D014246:Trichomonas vaginalis
D055815:Young Adult

China
18S rRNA,
Genetic variation,
Trichomonas vaginalis ,


Acute myeloid leukaemia in Western Australia 1991-2005: a retrospective population-based study of 898 patients regarding epidemiology, cytogenetics, treatment and outcome.

Abstract:
BACKGROUND
Patient characteristics and cytogenetics of acute myeloid leukaemia (AML) in clinical trials do not reflect that of the general population. There has not been a large population-based study that has examined cytogenetic features and outcomes of AML in Australia.

AIM
Investigation of epidemiological, prognostic, treatment and outcome data in adults diagnosed with AML in Western Australia between 1991 and 2005.

METHODS
Patients were identified utilising the Western Australia Cancer Registry, cytogenetic databases and hospital inpatient discharge diagnoses. Data were retrospectively collected from patients presenting to tertiary hospitals on patient characteristics, karyotype, induction therapy, remission, transplantation and survival.

RESULTS
A total of 987 patients with AML was identified, of which 91% (898) attended a tertiary hospital. Median age was 67 years and 45% of cases represented secondary AML. Cytogenetic analysis was available in 81% of patients. Frequent karyotypes were normal (38.8%), complex (13.8%) and -7/add(7q)/del(7q) (12.1%). Aggressive therapy was initiated in 62.6%. Less than 15% were enrolled in clinical trials. Overall 16.5% received a stem cell transplant. Median overall survival for all patients was 5.6 months. In patients treated aggressively, complete remission was achieved in 56.9% and median overall survival was 12.2 months. Age, secondary disease and karyotype were significantly predictive of remission and overall survival.

CONCLUSION
Age distribution, remission and survival rates were comparable with published population-based studies. High median age was reflected in the rate of secondary AML and trial eligibility. These findings highlight the need for prospective data collection.

Gangatharan|S A|SA|
Grove|C S|CS|
P'ng|S|S|
O'Reilly|J|J|
Joske|D|D|
Leahy|M F|MF|
Threlfall|T|T|
Wright|M P|MP|

acute myeloid leukaemia
Western Australia
cytogenetics
karyotype
survival
population study


Robotic Partial Nephrectomy: Update on Techniques.

Abstract: Surgical techniques for robot-assisted partial nephrectomy are driven by the aims of simplifying the most challenging surgical steps, maximizing functional and oncologic outcomes, and consistently pushing the envelope on possibilities. Over the past several years, we have seen an emergence in not only innovation in surgical technique, and robotic platforms, but integration of a variety of imaging techniques. We believe with developing robotic expertise, practicing urologists will continue to push the envelope in nephron preservation and complication-free recovery.

Bukavina|Laura|L| Mishra|Kirtishri|K| Calaway|Adam|A| Ponsky|Lee|L|

Robotic partial nephrectomy
Partial nephrectomy
Renal cell carcinoma
Selective artery clamping
Single site surgery


Effects of endurance cycling training on neuromuscular fatigue in healthy active men. Part II: Corticospinal excitability and voluntary activation.

Abstract: This study investigated the effects of 9-week endurance cycling training on central fatigability and corticomotor excitability of the locomotor muscles. Fourteen healthy participants undertook three incremental fatiguing cycling tests to volitional exhaustion (EXH): (i) before training (PRE), (ii) after training at the same absolute power output as PRE (POSTABS) and (iii) after training at the same percentage of V̇O2max as PRE (POSTREL). At baseline (i.e. before cycling), every 5 min during cycling and immediately at EXH, a neuromuscular evaluation including a series of 5-s knee extensions at 100, 75 and 50% of maximal voluntary knee extension (MVC) was performed. During each contraction, transcranial magnetic and peripheral nerve stimuli were elicited to obtain motor evoked potential (MEP), silent period (SP) and compound muscle action potential (Mmax) and to calculate voluntary activation (VA). The MEP·Mmax-1 ratio recorded from vastus lateralis at 100 and 50% MVC did not show any difference between conditions. At 75% MVC, MEP exhibited significantly lower values in POSTABS and POSTREL compared to PRE at baseline (P = 0.022 and P = 0.011, respectively) as well as at 25% of time to EXH of PRE (P = 0.022) for POSTREL. No adaptations, either at baseline or during cycling, were observed for VA and SPs. In conclusion, endurance training may result in some adaptations in the corticomotor responses when measured at rest or with low level of fatigue, yet these adaptations do not translate into attenuation of central fatigue at a similar cycling workload or at exhaustion.

Locomotor muscles
Brain
Central adaptation
Electromyography
Transcranial magnetic stimulation


Role of Cytochrome P450 Enzymes in Plant Stress Response.

Abstract: Cytochrome P450s (CYPs) are the largest enzyme family involved in NADPH- and/or O2-dependent hydroxylation reactions across all the domains of life. In plants and animals, CYPs play a central role in the detoxification of xenobiotics. In addition to this function, CYPs act as versatile catalysts and play a crucial role in the biosynthesis of secondary metabolites, antioxidants, and phytohormones in higher plants. The molecular and biochemical processes catalyzed by CYPs have been well characterized, however, the relationship between the biochemical process catalyzed by CYPs and its effect on several plant functions was not well established. The advent of next-generation sequencing opened new avenues to unravel the involvement of CYPs in several plant functions such as plant stress response. The expression of several CYP genes are regulated in response to environmental stresses, and they also play a prominent role in the crosstalk between abiotic and biotic stress responses. CYPs have an enormous potential to be used as a candidate for engineering crop species resilient to biotic and abiotic stresses. The objective of this review is to summarize the latest research on the role of CYPs in plant stress response.

cytochrome P450
plant stress response
antioxidants
plant metabolism


A Preliminary Study on the Establishment of the PDTX Model.

Abstract:
Objective
The current study aims to explore the establishment of the patient-derived tumor xenograft (PDTX) model.

Materials and Methods
Twenty patients with gastric cancer, 10 males and 10 females, were enrolled in the current study. Firstly, the volume, invasion and metastasis of the xenografts were observed. Subsequently, the correlation between tumor tissues of the PDTX mouse model and the patients' primary tumor tissues was evaluated by pathological H&E staining and immunohistochemistry.

Results
The results showed that the PDTX models corresponding to 15 of the 20 patients were successfully established, and the success rate of PDTX model establishment was 75%. Furthermore, the PDTX models maintained the differentiation degree, morphological characteristics and structural characteristics of tumor cells.

Conclusion
A PDTX model can be used as a substitute for cancer patients in clinical practice and may be suitable for clinical pharmacodynamic screening and new drug development.

Liu|Yong|Y| Zhu|Yan-Ping|YP| Cai|Ming-Zhi|MZ| Ke|Bin|B| Li|Bin|B| Liu|Ning|N| Xue|Qiang|Q| Zhan|Hong-Jie|HJ| Deng|Jing-Yu|JY| Zhang|Li|L| Hao|Yan-Peng|YP| Wang|Zhi-Qiang|ZQ| Wang|Li|L| Liang|Han|H|

PDTX
gastric tumor
xenotransplantation model


Cerebral functional asymmetry and phonological performance in dyslexic adults.

Abstract: Developmental dyslexia is a frequent language-based learning disorder characterized by difficulty in reading. The predominant etiologic view postulates that reading impairment is related to phonological and orthographic dysfunction. The aim of this fMRI study was to evaluate the neural bases of phonological processing impairment in remediated dyslexic adults (DD). We used a rhyming words judgment task contrasted with an unreadable fonts font-matching judgment task to compare patterns of activation and functional asymmetry in DD and normal-reading young adults. We found evidence of a link between asymmetry in inferior frontal gyrus and performance during the phonological processing. We also observed that DD recruit a network including regions involved in articulatory control in order to achieve rhyme judgment suggesting that, due to a lack of hemispheric specialization, DD recruit the latter network to achieve rhyme judgment.

Hernandez|N|N|
Andersson|F|F|
Edjlali|M|M|
Hommet|C|C|
Cottier|J P|JP|
Destrieux|C|C|
Bonnet-Brilhault|F|F|

Functional asymmetry
Adults
Developmental dyslexia
fMRI
Articulatory loop
French
Pars opercularis
Phonological task


Contribution of the TCF7L2 rs7903146 (C/T) gene polymorphism to the susceptibility to type 2 diabetes mellitus in Cameroon.

Abstract:
BACKGROUND
Data on the genetic variants for type 2 diabetes mellitus (T2DM) in sub-Saharan African populations are very scarce. This study aimed to investigate the association of transcription factor 7-like (TCF7L2) with T2DM in a Cameroonian population and explore possible genotype-phenotype correlation.

METHODS
This is a case-control study involving 37 T2DM patients and 37 non-diabetic volunteers of Cameroonian ethnicity aged 40 years old and above. We collected clinical and biological data to determine phenotypic traits. TCF7L2 was analyzed by genotyping for rs7903146 (C/T) using PCR-RFLP. Biochemical analyses were performed using a spectrophotometer with Chronolab kits. Statistical analyses were carried out using IBM SPSS, PS and Quanto.

RESULTS
TCF7L2 was associated with T2DM in this Cameroonian population (p = 0.013 for alleles, and p = 0.013 for genotypes). The risk allele was C (9.5% patients vs. 0% healthy controls, OR = 16.56) and the protective allele was T (90.5% patients vs. 100.0% healthy controls, OR = 0.06). The risk genotype was C/T (18.9% patients vs. 0% healthy controls, OR = 18.44), while the protective genotype was T/T (81.1% patients vs. 100.0% healthy controls, OR = 0.054). The statistical power was 99.99%. TCF7L2 was not preferentially associated with a specific disease phenotype.

CONCLUSION
TCF7L2 is associated with T2DM in this Cameroonian population. The association is not dependent on a specific T2DM phenotype. Clinical genetic testing for TCF7L2 can help to predict the occurrence of T2DM in Cameroon.

Guewo-Fokeng|Magellan|M|
Sobngwi|Eugene|E|
Atogho-Tiedeu|Barbara|B|
Donfack|Olivier Sontsa|OS|
Noubiap|Jean Jacques N|JJ|
Ngwa|Elvis Ndonwi|EN|
Mato-Mofo|Edith Pascale|EP|
Fosso|Priscille Pokam|PP|
Djahmeni|Eric|E|
Djokam-Dadjeu|Rosine|R|
Evehe|Marie-Solange|MS|
Aminkeng|Folefac|F|
Mbacham|Wilfred F|WF|
Mbanya|Jean Claude|JC|

Type 2 diabetes
Cameroon
Genetic association
Sub-Saharan Africa
Transcription factor 7-like 2 (TCF7L2)


Calcium Binding Ability of Recombinant Buffalo Regucalcin: A Study Using Circular Dichroism Spectroscopy.

Abstract: Regucalcin is a calcium regulating multifunctional protein reported to have many important functions like calcium homeostasis, anti-oxidative, anti-apoptotic and anti-cancerous functions. Although it is demonstrated as a calcium regulating protein, the calcium binding ability of regucalcin is still a controversy. The main reason for the controversy is that it lacks a typical EF hand motif which is common to most of the calcium binding proteins. Even though many studies reported regucalcin as a calcium binding protein, there are some studies reporting regucalcin as non-calcium binding also. In the present study, we investigated the calcium binding ability of recombinant buffalo regucalcin by assessing the secondary structural changes of the protein using circular dichroism spectroscopy after adding Ca2+ to the protein solution. Two types of calcium binding studies were done, one with different concentration of calcium chloride (0.5 mM CaCl2, 1 mM CaCl2, 2 mM CaCl2) and other at different time interval (no incubation and 10 min incubation) after addition of calcium chloride. Significant structural changes were observed in both studies which prove the calcium binding ability of recombinant regucalcin. A constant increase in the α-helix (1.1% with 0.5 mM CaCl2, 1.4% with 1 mM CaCl2, 3.5% with 2 mM CaCl2) and a decrease in β-sheets (78.5% with 0.5 mM CaCl2, 77.4% with 1 mM CaCl2, 75.7% with 2 mM CaCl2) were observed with the increase in calcium chloride concentration. There was a rapid increase in α-helix and decrease in β-sheets immediately after addition of calcium chloride, which subsides after 10 min incubation.

Harikrishna|P|P|
Thomas|Jobin|J|
Shende|A M|AM|
Bhure|S K|SK|

D047908:Intracellular Signaling Peptides and Proteins

Calcium binding
Buffalo
Circular dichroism
Recombinant regucalcin


High-risk epithelial ovarian cancer patients for hereditary ovarian cancer.

Abstract:
AIM
Risk assessment to identify patients at risk for hereditary ovarian cancer is important. The objectives of this study were to evaluate the frequency of high-risk epithelial ovarian cancer (EOC) patients and the frequency of germline mutation in these patients.

METHODS
A total of 335 patients with histologically confirmed non-mucinous EOC were included. High-risk patients were defined as patients who had: (i) significant family history of breast/ovarian/colorectal/endometrial cancers; (ii) synchronous breast/endometrial/colorectal cancer; or (iii) high-grade serous carcinoma. Germline mutation was evaluated by Next Generation Sequencing system with the 27-genes panel.

RESULTS
A total of 94 patients (28.1%) were high-risk patients, 5.1% had significant family history of cancers, 4.2% had synchronous primary cancers, and 22.1% had high-grade serous carcinoma. Germline mutation was detected in 10 of 35 patients (28.6%). Six germline mutations (17.1%) occurred in homologous recombination (HR) genes; these included three (8.6%) in BRCA1, one (2.9%) in BRCA2, and two (5.7%) in other HR genes (CHEK2 and RAD1C). Three patients (8.6%) had MMR gene mutations (one MLH1 and two MSH2) and one patient (2.9%) had other gene mutation (MUTYH). Of the 10 patients with germline mutation, 40% of patients had no significant family history of cancer.

CONCLUSION
Up to 30% of EOC patients had risk factors for hereditary ovarian cancer. Germline mutation was identified in 28.6% of patients (11.4% BRCA mutation, 5.7% other HR genes mutation, 8.6% MMR mutation, and 2.9% mutation in other gene). The high cost of genetic testing is an important barrier. Selected patients with high-risk factors might be initially considered for genetic testing in a limited-resource setting.

D020022:Genetic Predisposition to Disease

D009375:Neoplasms, Glandular and Epithelial

epithelial ovarian cancer
germline mutation
BRCA mutation
Thai


Occupational Noise Exposure and the Risk for Work-Related Injury: A Systematic Review and Meta-analysis.

Abstract:
Objectives
Occupational noise exposure has been linked to work-related injuries. Strategies to control occupational hazards often rely on dose-response relationships needed to inform policy, but quantitative synthesis of the relevant literature has not been done so far. This study aimed to systematically review the epidemiological literature and to perform meta-analysis of the risk for work-related injury due to occupational noise exposure.

Methods
PRISMA and MOOSE guidelines were followed. PubMed, ScienceDirect, and Google Scholar were searched up until 15 December 2016 in English, Russian, and Spanish. Reference lists, grey literature, and expert archives were searched as well. The risk of bias was assessed for each study and incorporated into the meta-analysis weights using the quality effects model.

Results
Overall, 21 studies were included at the qualitative review stage: 9 cross-sectional, 6 case-control, 4 cohort, 1 case-crossover, and 1 ecological. Noise exposure was assessed objectively in 13 studies. Information on occupational injuries was elicited from medical records/registry in 13 studies. Meta-analyses showed RR = 1.22 (95% CI: 1.15, 1.29) (n = 59028) per 5 dB increase in noise exposure (Cochran's Q = 27.26, P < 0.001, I2 = 67%) and RR = 2.16 (95% CI: 1.61, 2.90) (n = 96023) in the most exposed group (>90-95 dB) compared with the least exposed group (Cochran's Q = 180.46, P < 0.001, I2 = 90%). Subgroup analysis with meta-regression revealed an overall robust pooled risk per 5 dB.

Conclusions
There is a dose-response association between occupational noise exposure and work-related injury risk. However, the quality of evidence is 'very low'; therefore, the magnitude of this association should be interpreted with caution.

D003430:Cross-Sectional Studies
D006801:Humans
D009623:Noise, Occupational
D016273:Occupational Exposure
D060051:Occupational Injuries
D012044:Regression Analysis
D012306:Risk

accidents
sound
trauma
work environment
work performance


Molecular characterization and expression regulation of the factor-inhibiting HIF-1 (FIH-1) gene under hypoxic stress in bighead carp (Aristichthys nobilis).

Abstract: Factor-inhibiting HIF-1 (FIH-1) is an asparagine hydroxylase that interacts with hypoxia-inducible factor 1α (HIF-1α) to regulate transcriptional activity of HIF-1. Few studies of fish FIH-1 have been reported to date. In this study, the cDNA of FIH-1 gene was cloned and characterized for bighead carp, Aristichthys nobilis (AnFIH-1). The AnFIH-1 cDNA is 2065 bp in length, encoding a protein of 357 amino acid (aa) residues, which contains a JmjC homology region of the jumonji transcription factors. AnFIH-1 shares high identities with other vertebrate FIH-1 (79.1-96.4%), especially in the JmjC homology region, suggesting its conserved function. During the embryonic stages of A. nobilis, AnFIH-1 had significantly high expression levels in unfertilized egg and blastula. In healthy tissues, its predominant mRNA expression was detected in muscle. The mRNA levels of AnFIH-1 were significantly upregulated in the liver, gill, hypothalamus, and spleen after hypoxic treatment, and then decreased to pretreatment levels after 6-h re-oxygenation. However, in the muscle, continual increasing of mRNA expression was observed after hypoxic shock and re-oxygenation. These results indicate that FIH-1 may play an important role in physiological regulation for adapting to hypoxia stress in A. nobilis.

Feng|Xiu|X| Yu|Xiaomu|X| Pang|Meixia|M| Tong|Jingou|J|

Factor-inhibiting HIF-1
Aristichthys nobilis
Hypoxia
Gene expression


Recurrent desmoid tumor of the abdominal wall.

Abstract: Desmoid tumors most often occur in abdominal wall. Their tendency to recur lead to repeated operations which can make the abdominal wall reconstruction difficult. We report a 28-year-old female history. The patient was referred to our hospital for a recurrent desmoid tumor of the abdominal wall. The tumor was totally removed. The reconstruction was successful and the patient recovery was uneventful. Radical surgery still the mainstay of the desmoid tumors treatement. In abdominal wall location, the reconstruction can be a real challenge. Many procedures are discussed in literature. We used a double layer mesh covered by a fascial bepedicled flap. Taking into account their unpredictable behaviour and treatment complications, recurrent abdominal desmoid tumors can be managed simply and efficiently.

Toughrai|Imane|I|
Oufkir|Aya|A|
Laalim|Said Ait|SA|
Majdoub|Karim Ibn|KI|
Mazaz|Khalid|K|

D013505:Digestive System Surgical Procedures

Desmoid tumor
abdominal wall
reconstruction
recurrent tumor


Synthesis, self-assembly and anticancer drug encapsulation and delivery properties of cyclodextrin-based giant amphiphiles.

Abstract: Cyclodextrin-calixarene giant amphiphiles that can self-assemble into nanospheres or nanovesicles have the ability to encapsulate the anticancer hydrophobic drugs docetaxel, temozolomide and combretastatin A-4 with encapsulation efficiencies >80% and deliver them to tumoral cells, enhancing their therapeutic efficacy by 1-3 orders of magnitude. These amphiphiles were modified by inserting a disulfide bridge confering them redox responsiveness. Disassembly of the resulting nanocompounds and cargo release was favored by high glutathione levels mimicking those present in the tumor microenvironment. Anticancer drug-loaded nanoformulations inhibited prostate, breast, glioblastoma, colon or cervix cancer cell lines proliferation with IC50 values markedly below those observed for the free drugs. Cell-cycle analysis indicated a similar mechanism of action for drug-loaded nanocompounds and free drugs. The results strongly suggest that the cyclodextrin-calixarene heterodimer prototype is an excellent scaffold for nanoformulations aimed to deliver anticancer drugs with limited bioavailability due to low solubility to tumoral cells, markedly increasing their effectivity.

Gallego-Yerga|Laura|L|
de la Torre|Cristina|C|
Sansone|Francesco|F|
Casnati|Alessandro|A|
Mellet|Carmen Ortiz|CO|
García Fernández|José M|JM|
Ceña|Valentín|V|

D057927:Hydrophobic and Hydrophilic Interactions

drug encapsulation
cancer
Cyclodextrins
calixarenes
drug delivery
mitosis inhibitors


Fibre reinforcement in a structurally compromised endodontically treated molar: a case report.

Abstract: The reconstruction of structurally compromised posterior teeth is a rather challenging procedure. The tendency of endodontically treated teeth (ETT) to fracture is considerably higher than vital teeth. Although posts and core build-ups followed by conventional crowns have been generally employed for the purpose of reconstruction, this procedure entails sacrificing a considerable amount of residual sound enamel and dentin. This has drawn the attention of researchers to fibre reinforcement. Fibre-reinforced composite (FRC), designed to replace dentin, enables the biomimetic restoration of teeth. Besides improving the strength of the restoration, the incorporation of glass fibres into composite resins leads to favorable fracture patterns because the fibre layer acts as a stress breaker and stops crack propagation. The following case report presents a technique for reinforcing a badly broken-down ETT with biomimetic materials and FRC. The proper utilization of FRC in structurally compromised teeth can be considered to be an economical and practical measure that may obviate the use of extensive prosthetic treatment.

Soares|Renita|R|
de Ataide|Ida de Noronha|Ide N|
Fernandes|Marina|M|
Lambor|Rajan|R|

Reinforcement
Endodontically treated teeth
Biodentine
Fibre reinforced composite


Synthesis, structures, molecular docking, cytotoxicity and bioimaging studies of two novel Zn(II) complexes.

Abstract: Two novel compounds [Zn2(Endc)2(bipy)2(H2O)3]·4(H2O)·2(O)(1), [Zn2(Endc)2(phen)2(H2O)]·(O)(2) (bipy = 2,2-bipyridine, phen = 1,10-phenanthroline, and Endc = endo-norbornene-cis-5,6-dicarboxylicacid) have been synthesized and characterized. In this paper abbreviations are FS-DNA (fish sperm DNA), HeLa (human cervix epithelia carcinoma cells), KB (human oral epithelial carcinoma cells), LO2 (human liver cell L-O2), EtBr (ethidium bromide), DMF (Dimethyl Formamide), MTT ([3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium]). The binding of complexes with Fish Sperm DNA were measured by electronic absorption spectra and fluorescence spectroscopy. The ability of these complexes to cleave the pBR322 plasmid DNA or the KB and HeLa DNA extracted in our laboratory was demonstrated by gel electrophoresis assay. The cytotoxic effects of these complexes were examined on two tumor cell lines, HeLa, KBr and one normal cell line LO-2. UV absorption and fluorescence spectra indicate the ability of the complexes bond to DNA with different binding affinity. Gel electrophoresis assay demonstrates which one complex more effective DNA-cleavage activity. The cytotoxic activity of the complexes was tested against two different cancer and one normal cell lines. The two complexes exhibited cytotoxic specificity and significant cancer cell inhibitory rate and lower cytotoxicity toward the normal cell lines. The unique interaction mode with DNA and cancer cells inhibition effect clearly revealed the relationship between the structure and the activity of the novel antitumor agent Zn(II) complexes.

Gao|Enjun|E| Sun|Na|N| Zhang|Shaozhong|S| Ding|Yuqing|Y| Qiu|Xue|X| Zhan|Yang|Y| Zhu|Mingchang|M|

Cytotoxicity
Apoptosis
DNA binding
HeLa and KB cells


The potential value of surrogate performance markers at caesarean section for the assessment of surgical competence.

Abstract:
OBJECTIVES
We hypothsised that surrogate markers of competence (procedure time and estimated surgical blood loss) could be of value when assessing competence for trainees learning to undertake lower segment caesarean section (LSCS). The study aim was to investigate differences in surrogate markers of surgical competence at LSCS between different training grades of primary surgeon and for different grades of surgical assistant; to assess the potential value of using these surrogate markers in overall assessments of surgical competence.

STUDY DESIGN
Operating records for elective LSCS were reviewed from January 2007 to January 2015. Uncomplicated LSCS where a junior trainee (ST2/ST3) or a senior trainee (ST6+) was the primary surgeon were included. Inclusion criteria were LSCS with body mass index less than 35, singleton pregnancy, greater than 34 weeks' gestation, no more than one previous caesarean section and no low-lying placenta. Procedure time, estimated blood loss and the effect of the grade of surgical assistant (consultant or trainee) on these were compared overall for all surgeons at ST2 level, ST3 level and senior level (ST6+) using Student's t test and effect size calculation (Cohen test).

RESULTS
During the study period 3099 uncomplicated LSCS were performed by 60 trainees: 1367 by ST2, 1085 by ST3 and 646 by senior trainees (ST6+). Mean procedure times and recorded estimated blood loss decreased significantly for each level of training (p < 0.05). The degree of experience of the surgical assistant was also associated with reduced procedure times and blood loss, this was significant for trainees in ST2 when assisted by a consultant (p < 0.05).

CONCLUSIONS
Training progression is associated with a reduction in procedure time and estimated blood loss, which are both surrogate markers of competence at LSCS. Current objective structured assessments of technical competence for trainees (OSATS) do not take these metrics into account when assessing performance. An enhanced assessment of trainees undertaking LSCS is suggested, reviewing both objective structured assessments of technical performance (OSATS) and surrogate markers of performance recorded in a surgical logbook to provide a more comprehensive assessment of overall competence.

D016063:Blood Loss, Surgical
D002585:Cesarean Section
D002983:Clinical Competence
D004503:Education, Medical, Graduate
D004521:Educational Measurement
D005260:Female
D006801:Humans
D061646:Operative Time
D011247:Pregnancy

Caesarean section
Clinical competence
Medical education
Obstetrics


A Note on the Tracing of Herbage Contribution to Grazing Sheep Diet Using Milk and Feces Biomarkers.

Abstract: Milk from grazing ruminants is usually rich in beneficial components for human health, but distinguishing milks sourced from grazing is difficult, and this hinders the valuing of the grazing benefit. This study aimed at evaluating the ability of milk biomarkers (1) to trace milks sourced from sheep submitted to different access times (ATs) to pasture and (2) to estimate sheep herbage dry matter intake (HDMI, g DM ewe-1 d-1) and herbage percentage (HP, % DM) in sheep diet. Animal data derive from a published experiment in which six replicated groups of mid-lactation Sarda sheep had ATs of 2, 4, or 6 h d-1 to a ryegrass pasture. Sheep HDMI and HP of each group were measured on four dates in April 2013. Group milk was sampled, and milk fatty acids (FAs) and n-alkanes were determined by gas chromatography. The latter markers were also measured in feces samples bulked by group. The data (N = 24 records) were submitted to Linear Discriminant Analysis (LDA) aimed at distinguishing the AT to pasture based on biomarkers previously selected by Genetic Algorithms (GA). Partial Least Square Regression (PLSR) models were used to estimate HDMI and HP using biomarkers selected by GA. Based on one milk alkane and six milk FAs as biomarkers, estimates of the AT using GA-LDA were 95.8% accurate. The estimation of HDMI by GA-PLSR based on five milk FAs was moderately precise [explained variance = 75.2%; percentage of the residual mean square error of cross-validation over the mean value (RMSECV%) = 15.0%]. The estimation of HP by GA-PLSR based on 1 milk alkane and 10 FAs was precise (explained variance = 80.8%; RMSECV% = 7.4%). To conclude, these preliminary results suggest that milks sourced from sheep flocks with AT to pasture differentiated by 2 h in the range 2-6 h d-1 can be precisely discriminated using milk biomarkers. The contribution of herbage to sheep diet can also be precisely estimated.

Molle|Giovanni|G| Cabiddu|Andrea|A| Decandia|Mauro|M| Acciaro|Marco|M| Scanu|Giuseppe|G| Addis|Margherita|M| Fiori|Myriam|M| Caredda|Marco|M|

pasture
fatty acids
alkanes
authentication
chemometrics
dairy sheep
nutrition
traceability


Using a divided-attention stepping accuracy task to improve balance and functional outcomes in an individual with incomplete spinal cord injury: A case report.

Abstract: A spinal cord injury (SCI) frequently results in impaired balance, endurance, and strength with subsequent limitations in functional mobility and community participation. The purpose of this case report was to implement a training program for an individual with a chronic incomplete SCI using a novel divided-attention stepping accuracy task (DASAT) to determine if improvements could be made in impairments, activities, and participation. The client was a 51-year-old male with a motor incomplete C4 SCI sustained 4 years prior. He presented with decreased quality of life (QOL) and functional independence, and deficits in balance, endurance, and strength consistent with central cord syndrome. The client completed the DASAT intervention 3 times per week for 6 weeks. Each session incorporated 96 multi-directional steps to randomly-assigned targets in response to 3-step verbal commands. QOL, measured using the SF-36, was generally enhanced but fluctuated. Community mobility progressed from close supervision to independence. Significant improvement was achieved in all balance scores: Berg Balance Scale by 9 points [Minimal Detectable Change (MDC) = 4.9 in elderly]; Functional Reach Test by 7.62 cm (MDC = 5.16 in C5/C6 SCI); and Timed Up-and-Go by 0.53 s (MDC not established). Endurance increased on the 6-Minute Walk Test, with the client achieving an additional 47 m (MDC = 45.8 m). Lower extremity isokinetic peak torque strength measures were mostly unchanged. Six minutes of DASAT training per session provided an efficient, low-cost intervention utilizing multiple trials of variable practice, and resulted in better performance in activities, balance, and endurance in this client.

Leach|Susan J|SJ|
Magill|Richard A|RA|
Maring|Joyce R|JR|

D001288:Attention
D001696:Biomechanical Phenomena
D002574:Cervical Vertebrae
D002908:Chronic Disease
D051341:Dependent Ambulation
D005080:Exercise Test
D017079:Exercise Tolerance
D006801:Humans
D008297:Male
D008875:Middle Aged
D051346:Mobility Limitation
D009043:Motor Activity
D053580:Muscle Strength
D026741:Physical Therapy Modalities
D004856:Postural Balance
D011788:Quality of Life
D020127:Recovery of Function
D013119:Spinal Cord Injuries
D019415:Torque
D016896:Treatment Outcome

spinal cord injury
variable practice
Procedural learning


How Soil Biota Drive Ecosystem Stability.

Abstract: High biodiversity aboveground tends to increase the stability of ecosystem functioning when faced with a changing environment. However, whether and how soil biota affect ecosystem stability is less clear. Here, we introduce a framework for understanding the effects of soil biota on variation in ecosystem functioning under environmental changes. We conclude that soil biota may be a neglected factor determining ecosystem stability through their direct and indirect effects on plant diversity, the net productivity of an ecosystem, and compensatory dynamics among plant species, and via altering ecosystem resistance and resilience. Furthermore, future research needs to consider that effects of soil biota on ecosystem stability will vary depending on extrinsic factors, and for a given perturbation and ecosystem function.

Yang|Gaowen|G|
Wagg|Cameron|C|
Veresoglou|Stavros D|SD|
Hempel|Stefan|S|
Rillig|Matthias C|MC|

ecosystem resistance and resilience
arbuscular mycorrhizal fungi
diversity–stability relationships
invariability
species asynchrony


Chronic myeloid leukemia presenting in lymphoblastic crisis, a differential diagnosis with Philadelphia-positive B-lymphoblastic leukemia.

Abstract: Rare patients with chronic myeloid leukemia (CML) can present initially in lymphoblastic crisis (LBC) mimicking Ph + B-lymphoblastic leukemia (B-ALL). We retrospectively reviewed 275 adults who diagnosed initially as Ph + B-ALL and identified 28 patients with at least one of three features supporting the diagnosis of CML-LBC: 1) a large discrepancy between the blast count and Ph + clone; 2) Ph + clone persistent when B-ALL in remission; 3) BCR/ABL1 fusion detected in segmented cells. BCR-ABL1 fusions were p210 in 25 patients and p190 in 3 patients. In comparison to patients with Ph + B-ALL, patients with CML-LBC were older; had higher leukocyte and absolute neutrophil counts; higher immature myeloid cells in peripheral blood; lower blast counts; and inferior outcomes. In addition, we prospectively analyzed 26 patients with Ph + B-lymphoblastic leukemia and identified 8 patients with features more consistent with CML-LBC. These findings highlight the importance of distinguishing CML-LBC from de novo Ph + B-ALL.

Chen|Zhining|Z|
Hu|Shimin|S|
Wang|Sa A|SA|
Konopleva|Marina|M|
Tang|Zhenya|Z|
Xu|Jie|J|
Li|Shaoying|S|
Toruner|Gokce|G|
Thakral|Beenu|B|
Medeiros|L Jeffrey|LJ|
Tang|Guilin|G|0000-0002-9482-4806

D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive

D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma

Chronic myeloid leukemia
lymphoblastic crisis
B-lymphoblastic leukemia
Philadelphia chromosome


Fatal Eosinophilic Myocarditis in a Healthy 17-Year-Old Male with Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2c).

Abstract: Background: Cardiac damage is frequently referred to in patients with SARS-CoV-2, is usually diagnosed by enzyme elevations, and is generally thought to be due to underlying coronary artery disease. There are references to cardiomyopathies accompanying coronavirus, but there has been no histologic confirmation.Case report: A previously healthy 17 year male old presented in full cardiac arrest to the emergency department after a 2 day history of headache, dizziness, nausea and vomiting. Autopsy demonstrated an enlarged flabby heart with eosinophilic myocarditis. There was no interstitial pneumonia or diffuse alveolar damage. Postmortem nasopharyngeal swabs detected severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) known to cause coronavirus disease 2019 (COVID-19). No other cause for the eosinophilic myocarditis was elucidated.Conclusion: Like other viruses, SARS-CoV-2 may be associated with fulminant myocarditis.

Craver|Randall|R| Huber|Samantha|S| Sandomirsky|Marrianna|M| McKenna|Dwight|D| Schieffelin|John|J| Finger|Leron|L|

severe respiratory syndrome coronavirus 2


Prevention and management of aggressive behaviour in patients at psychiatric hospitals: a document analysis of clinical practice guidelines in Hong Kong.

Abstract: Patient aggressive behaviour remains a significant public health concern worldwide. The use of restraint and seclusion remains a last resort but not an uncommon practice in clinical psychiatry in the management of aggressive events. There seems to be a paucity of evidenced-based research examining the policy framework guiding the use of restraint and seclusion in Asia contexts. The purpose of this study was to conduct an analysis on the guidelines in psychiatric hospitals in Hong Kong, and to explore the extent to which these guidelines were aligned with the international clinical guidelines for the prevention and management of patient aggression in psychiatry. A descriptive document analysis was used to analyse the guidelines from four psychiatric hospitals in Hong Kong in comparison with the NICE (National Institute of Health and Care Excellence UK) guidelines. Data were collected from December 2017 to June 2018. A total of 91 written documents were retrieved. Preventing violence and aggression has the highest level of agreement (31%,) while the use of restrictive interventions has the lowest level of agreement (12%). The sub-recommendation with most in line with the NICE guidelines were restrictive interventions, de-escalation, and improving service users' experiences. However, for example, staff training, working with police, and reduced use of restrictive interventions seemed to have no agreement with the NICE guidelines. Variation exists between the Asian (Hong Kong) local policy framework/guidelines and the European (UK) national policy framework. There are also large discrepancies in the written guidelines on patient aggressive behaviour when comparing local policy frameworks, cluster-based documents, and departmental practices.

aggression
psychiatric hospital
document analysis
restraint
seclusion
violence


Expectations for the Development of Health Technology Assessment in Brazil.

Abstract: The implementation of health technology assessment (HTA) in emerging countries depends on the characteristics of the health care system and the needs of public health care. The objective of this survey was to investigate experts' expectations for the development of HTA in Brazil and to derive measures to strengthen the impact of HTA in Brazil on health care decisions. Based on a scoping literature review, a questionnaire was developed proposing eight theses for seven domains of HTA: (i) capacity building, (ii) public involvement, (iii) role of cost-effectiveness analysis (CEA), (iv) institutional framework, (v) scope of HTA studies, (vi) methodology of HTA, and (vii) HTA as the basis for jurisdiction. Thirty experts responded in full to the survey and agreed to five of the eight theses proposed. Experts suggested several measures to promote HTA within the scope of each domain, thus addressing capacity building related to HTA, availability, and reliability of population data, and legal endowment of the HTA system. Finally, HTA processes in Brazil should also address public health issues (e.g., appraisal of interventions directed at chronic diseases).

health technology assessment
Brazil
decision making
health services research
redesign
surveys and questionnaires


Interfacial microscopic examination and chemical analysis of resin-dentin interface of self-adhering flowable resin composite.

Abstract: Background: The newly introduced self-adhering flowable resin-composites decrease the required time for application by incorporation of an acidic adhesive monomer, thus reducing the number of the steps, but its bonding is still uncertain. The aim of this study was to evaluate the interfacial microscopic examination and chemical analysis at the resin-dentin interface of a self-adhering flowable resin composite (Vertise-Flow) versus a total-etch (Te-Econom Plus) resin composite, using an etching agent (Eco-Etch gel) and  bonding agent (Single Bond Universal). Methods: Sixteen freshly extracted sound human posterior teeth were used. The teeth were randomly divided into two groups: 8 specimens per type of composite. Standard-shaped class V cavities were prepared on the buccal surface. One group was restored by Te-Econom Plus resin composite by total-etch technique using Eco-Etch gel, which was applied to dentine for 15 seconds, followed by rinsing, drying and bonding agent application (Single Bond Universal). The other group restored directly with self-adhering resin composite (Vertise-Flow) without application of etch or bond. Curing was done for 20 seconds using a light emitting diode light curing unit. Evaluation of the resin-dentin interface was done microscopically by examination of marginal gap distance in μm using scanning electron microscope (SEM), and chemical analysis of silver particles was observed using SEM with energy-dispersive X-ray spectrometry after 24 hours of specimen storage in ammoniacal silver nitrate. Results: Regarding marginal gap distance (µm) and silver atomic % mean values, teeth restored with self-adhering resin composite (Vertise-Flow) showed significantly higher mean values than the multi-step etch and rinse resin composite group (5.2 vs 0; 12.2 vs 8.2, respectively). Conclusions: Resin-dentin bonding using total-etch resin composite technique was more effective than self-adhering flowable resin composite (Vertise-Flow) regarding marginal gap formation and penetration of silver particles. Further studies for bond strength could be performed.

resin-dentin interface
Self-adhering
resin composite
total-etch
gap distance
bonding system


Glycosylation characterization of recombinant human erythropoietin produced in glycoengineered Pichia pastoris by mass spectrometry.

Abstract: Glycosylation plays a critical role in the in vivo efficacy of both endogenous and recombinant erythropoietin (EPO). Using mass spectrometry, we characterized the N-/O-linked glycosylation of recombinant human EPO (rhEPO) produced in glycoengineered Pichia pastoris and compared with the glycosylation of Chinese hamster ovary (CHO) cell-derived rhEPO. While the three predicted N-linked glycosylation sites (Asn24, Asn38 and Asn83) showed complete site occupancy, Pichia- and CHO-derived rhEPO showed distinct differences in the glycan structures with the former containing sialylated bi-antennary glycoforms and the latter containing a mixture of sialylated bi-, tri- and tetra-antennary structures. Additionally, the N-linked glycans from Pichia-produced rhEPO were similar across all three sites. A low level of O-linked mannosylation was detected on Pichia-produced rhEPO at position Ser126, which is also the O-linked glycosylation site for endogenous human EPO and CHO-derived rhEPO. In summary, the mass spectrometric analyses revealed that rhEPO derived from glycoengineered Pichia has a highly uniform bi-antennary N-linked glycan composition and preserves the orthogonal O-linked glycosylation site present on endogenous human EPO and CHO-derived rhEPO.

Gong|Bing|B|
Burnina|Irina|I|
Stadheim|Terrance A|TA|
Li|Huijuan|H|

D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization

Pichia pastoris
mass spectrometry
rhEPO
N-linked glycosylation
O-linked glycosylation


Unilateral Blurred Vision as the Sole Presenting Symptom of Chronic Lymphocytic Leukemia.

Abstract:
Purpose
To describe a case of infiltrative optic neuropathy caused by chronic lymphocytic leukemia.

Case Report
A 41-year-old white male presented with painless, blurry vision in the left eye. Examination revealed unilateral optic nerve swelling confirmed by optical coherence tomography (OCT). Initial workup revealed mild leukocytosis, eventually diagnosed as chronic lymphocytic leukemia (CLL). No other cause of optic neuropathy was identified despite extensive investigation. The patient developed rapidly progressive retinal ganglion cell nerve fiber layer (NFL) atrophy and relative afferent pupillary defect (RAPD) of the left eye despite steroid treatment but stabilized after four cycles of CLL-targeted chemotherapy. Although infiltrative optic neuropathy is well-known in leukemia, presentation with only subtle vision loss is rare. Vision loss usually presents late in leukemic infiltrative optic neuropathy and therefore must be considered in patients with optic disc swelling and leukocytosis.

Conclusion
When treating CLL, progressive visual decline with coexistent optic neuropathy may warrant chemotherapy.

Chronic Lymphocytic Leukemia
Optic Neuropathy