Transportation Characteristics of Bisphenol A Affected by Humic Substances Through Ultrafiltration Membrane with Low Molecule Weight Cut-Off

The hydrophobic interaction properties between bisphenol A (BPA) and humic substances (HS) were investigated using an ultrafiltration (UF) membrane with 1000Da Molecule Weight Cut-off (MWCO). Expect for other influences, the Stokes radius of the hydration molecule of the BPA affected by HS was calculated with the hydrodynamic model by simulation of BPA transportation in the membrane. It was found that the rejection efficiencies of BPAs visibly increased in the presence of various HS (humic acid and fulvic acid). Simulation results showed that the effective radius of the hydration molecules was increased accordingly. It is proposed that the HS addition may improve the hydrophobicity and hydration of the BPA hydration molecules, which increased the effective radius of the BPA molecules. This research helps to understand the interaction between hydrophobic molecules and natural organic matters (NOMs) during the removal of emerging hydrophobic contaminants using a membrane with low MWCO

Association of low‐activity ALDH2 and alcohol consumption with risk of esophageal cancer in Chinese adults: A population‐based cohort study

Existing evidence remains inconclusive as to how the association between inactive ALDH2 and esophageal cancer (EC)depends on alcohol consumption. The study is based on the China Kadoorie Biobank cohort, with 10 years follow-up of 0.5million adults aged 30–79 years. ALDH2 activity was assessed by both self-reported flushing response and Glu504Lys(rs671 G>A) polymorphism. Among both male and female participants who consumed alcohol less than weekly(n569,519; 211 EC cases), low active or inactive ALDH2 was not associated with increased EC risk [HRs (95% CIs): GAvs.GG 0.75 (0.54, 1.04); AAvs. GG 1.01 (0.46, 2.20)]. Among male weekly alcohol consumers, both flushing response[n559,380; 501 EC cases; HRs (95% CIs): “soon after drinking”vs. “no” flushing response 1.45 (1.05, 2.01)] and rs671[n510,692; 94 EC cases; GAvs. GG 3.31 (1.94, 5.67)] were associated with EC risk. The increased EC risk associated with“soon” response or rs671 GA was apparent in men consuming alcohol≥30g/d. Among male daily consumers, the HRs(95% CIs) for EC associated with 15g/d of alcohol were 1.28 (1.15, 1.44) for “soon” response [vs. other responses: 1.12(1.09, 1.15);pinteraction50.047;n536,401, 425 EC cases] and 1.41 (1.08, 1.82) for rs671 GA [vs. GG: 1.16 (1.06, 1.27);pinteraction50.493;n56,607, 80 EC cases]. Self-reported flushing response had low sensitivity (56.8%) and high specificity(88.4%) in identifying rs671 A allele among male weekly alcohol consumers. In conclusion, low-activity ALDH2 was associ-ated with increased EC risk among male heavy alcohol consumers. More accurate measurement of alcohol-related EC riskallows better achievement of precision prevention

Failure to prescribe pneumocystis prophylaxis is associated with increased mortality, even in the cART era: results from the Treat Asia HIV observational database

<p>Abstract</p> <p>Background</p> <p>Pneumocystis jiroveci pneumonia (PCP) prophylaxis is recommended for patients with CD4 counts of less than 200 cells/mm³. This study examines the proportion of patients in the TREAT Asia HIV Observational Database (TAHOD) receiving PCP prophylaxis, and its effect on PCP and mortality.</p> <p>Methods</p> <p>TAHOD patients with prospective follow up had data extracted for prophylaxis using co-trimoxazole, dapsone or pentamidine. The proportion of patients on prophylaxis was calculated for each calendar year since 2003 among patients with CD4 counts of less than 200 cells/mm³. The effect of prophylaxis on PCP and survival were assessed using random-effect Poisson regression models.</p> <p>Results</p> <p>There were a total of 4050 patients on prospective follow up, and 90% of them were receiving combination antiretroviral therapy. Of those with CD4 counts of less than 200 cells/mm³, 58% to 72% in any given year received PCP prophylaxis, predominantly co-trimoxazole. During follow up, 62 patients developed PCP (0.5 per 100 person-years) and 169 died from all causes (1.36/100 person-years). After stratifying by site and adjusting for age, CD4 count, CDC stage and antiretroviral treatment, those without prophylaxis had no higher risk of PCP, but had a significantly higher risk of death (incident rate ratio 10.8, p < 0.001). PCP prophylaxis had greatest absolute benefit in patients with CD4 counts of less than 50 cells/mm³, lowering mortality rates from 33.5 to 6.3 per 100 person-years.</p> <p>Conclusions</p> <p>Approximately two-thirds of TAHOD patients with CD4 counts of less than 200 cells/mm³received PCP prophylaxis. Patients without prophylaxis had significantly higher mortality, even in the era of combination ART. Although PCP may be under-diagnosed, these data suggest that prophylaxis is associated with important survival benefits.</p

Guidelines for burn rehabilitation in China

Abstract Quality of life and functional recovery after burn injury is the final goal of burn care, especially as most of burn patients survive the injury due to advanced medical science. However, dysfunction, disfigurement, contractures, psychological problems and other discomforts due to burns and the consequent scars are common, and physical therapy and occupational therapy provide alternative treatments for these problems of burn patients. This guideline, organized by the Chinese Burn Association and Chinese Association of Burn Surgeons aims to emphasize the importance of team work in burn care and provide a brief introduction of the outlines of physical and occupational therapies during burn treatment, which is suitable for the current medical circumstances of China. It can be used as the start of the tools for burn rehabilitation.</jats:p

Biallelic mutations in SORD cause a common and potentially treatable hereditary neuropathy with implications for diabetes

Here we report biallelic mutations in the sorbitol dehydrogenase gene (SORD) as the most frequent recessive form of hereditary neuropathy. We identified 45 individuals from 38 families across multiple ancestries carrying the nonsense c.757delG (p.Ala253GlnfsTer27) variant in SORD, in either a homozygous or compound heterozygous state. SORD is an enzyme that converts sorbitol into fructose in the two-step polyol pathway previously implicated in diabetic neuropathy. In patient-derived fibroblasts, we found a complete loss of SORD protein and increased intracellular sorbitol. Furthermore, the serum fasting sorbitol levels in patients were dramatically increased. In Drosophila, loss of SORD orthologs caused synaptic degeneration and progressive motor impairment. Reducing the polyol influx by treatment with aldose reductase inhibitors normalized intracellular sorbitol levels in patient-derived fibroblasts and in Drosophila, and also dramatically ameliorated motor and eye phenotypes. Together, these findings establish a novel and potentially treatable cause of neuropathy and may contribute to a better understanding of the pathophysiology of diabetes

Particulate matter exposure during pregnancy is associated with birth weight, but not gestational age, 1962-1992: a cohort study

<p>Abstract</p> <p>Background</p> <p>Exposure to air pollutants is suggested to adversely affect fetal growth, but the evidence remains inconsistent in relation to specific outcomes and exposure windows.</p> <p>Methods</p> <p>Using birth records from the two major maternity hospitals in Newcastle upon Tyne in northern England between 1961 and 1992, we constructed a database of all births to mothers resident within the city. Weekly black smoke exposure levels from routine data recorded at 20 air pollution monitoring stations were obtained and individual exposures were estimated via a two-stage modeling strategy, incorporating temporally and spatially varying covariates. Regression analyses, including 88,679 births, assessed potential associations between exposure to black smoke and birth weight, gestational age and birth weight standardized for gestational age and sex.</p> <p>Results</p> <p>Significant associations were seen between black smoke and both standardized and unstandardized birth weight, but not for gestational age when adjusted for potential confounders. Not all associations were linear. For an increase in whole pregnancy black smoke exposure, from the 1^st(7.4 μg/m³) to the 25^th(17.2 μg/m³), 50^th(33.8 μg/m³), 75^th(108.3 μg/m³), and 90^th(180.8 μg/m³) percentiles, the adjusted estimated decreases in birth weight were 33 g (SE 1.05), 62 g (1.63), 98 g (2.26) and 109 g (2.44) respectively. A significant interaction was observed between socio-economic deprivation and black smoke on both standardized and unstandardized birth weight with increasing effects of black smoke in reducing birth weight seen with increasing socio-economic disadvantage.</p> <p>Conclusions</p> <p>The findings of this study progress the hypothesis that the association between black smoke and birth weight may be mediated through intrauterine growth restriction. The associations between black smoke and birth weight were of the same order of magnitude as those reported for passive smoking. These findings add to the growing evidence of the harmful effects of air pollution on birth outcomes.</p

AI is a viable alternative to high throughput screening: a 318-target study

: High throughput screening (HTS) is routinely used to identify bioactive small molecules. This requires physical compounds, which limits coverage of accessible chemical space. Computational approaches combined with vast on-demand chemical libraries can access far greater chemical space, provided that the predictive accuracy is sufficient to identify useful molecules. Through the largest and most diverse virtual HTS campaign reported to date, comprising 318 individual projects, we demonstrate that our AtomNet® convolutional neural network successfully finds novel hits across every major therapeutic area and protein class. We address historical limitations of computational screening by demonstrating success for target proteins without known binders, high-quality X-ray crystal structures, or manual cherry-picking of compounds. We show that the molecules selected by the AtomNet® model are novel drug-like scaffolds rather than minor modifications to known bioactive compounds. Our empirical results suggest that computational methods can substantially replace HTS as the first step of small-molecule drug discovery

Cardiovascular disease, chronic kidney disease, and diabetes mortality burden of cardiometabolic risk factors from 1980 to 2010: A comparative risk assessment

Background: High blood pressure, blood glucose, serum cholesterol, and BMI are risk factors for cardiovascular diseases and some of these factors also increase the risk of chronic kidney disease and diabetes. We estimated mortality from cardiovascular diseases, chronic kidney disease, and diabetes that was attributable to these four cardiometabolic risk factors for all countries and regions from 1980 to 2010. Methods: We used data for exposure to risk factors by country, age group, and sex from pooled analyses of population-based health surveys. We obtained relative risks for the effects of risk factors on cause-specific mortality from meta-analyses of large prospective studies. We calculated the population attributable fractions for each risk factor alone, and for the combination of all risk factors, accounting for multicausality and for mediation of the effects of BMI by the other three risks. We calculated attributable deaths by multiplying the cause-specific population attributable fractions by the number of disease-specific deaths. We obtained cause-specific mortality from the Global Burden of Diseases, Injuries, and Risk Factors 2010 Study. We propagated the uncertainties of all the inputs to the final estimates. Findings: In 2010, high blood pressure was the leading risk factor for deaths due to cardiovascular diseases, chronic kidney disease, and diabetes in every region, causing more than 40% of worldwide deaths from these diseases; high BMI and glucose were each responsible for about 15% of deaths, and high cholesterol for more than 10%. After accounting for multicausality, 63% (10·8 million deaths, 95% CI 10·1-11·5) of deaths from these diseases in 2010 were attributable to the combined effect of these four metabolic risk factors, compared with 67% (7·1 million deaths, 6·6-7·6) in 1980. The mortality burden of high BMI and glucose nearly doubled from 1980 to 2010. At the country level, age-standardised death rates from these diseases attributable to the combined effects of these four risk factors surpassed 925 deaths per 100 000 for men in Belarus, Kazakhstan, and Mongolia, but were less than 130 deaths per 100 000 for women and less than 200 for men in some high-income countries including Australia, Canada, France, Japan, the Netherlands, Singapore, South Korea, and Spain. Interpretation: The salient features of the cardiometabolic disease and risk factor epidemic at the beginning of the 21st century are high blood pressure and an increasing effect of obesity and diabetes. The mortality burden of cardiometabolic risk factors has shifted from high-income to low-income and middle-income countries. Lowering cardiometabolic risks through dietary, behavioural, and pharmacological interventions should be a part of the global response to non-communicable diseases. Funding: UK Medical Research Council, US National Institutes of Health. © 2014 Elsevier Ltd

Proton reconstruction with the CMS-TOTEM Precision Proton Spectrometer

The Precision Proton Spectrometer (PPS) of the CMS and TOTEM experiments collected 107.7 fb 1 in proton-proton (pp) collisions at the LHC at 13 TeV(Run 2). This paper describes the key features of the PPS alignment and optics calibrations, the proton reconstruction procedure, as well as the detector efficiency and the performance of the PPS simulation. The reconstruction and simulation are validated using a sample of (semi)exclusive dilepton events. The performance of PPS has proven the feasibility of continuously operating a near-beam proton spectrometer at a high luminosity hadron collider