Recent Aspects on the Pathogenesis Mechanism, Animal Models and Novel Therapeutic Interventions for Middle East Respiratory Syndrome Coronavirus Infections

Middle East Respiratory Syndrome Coronavirus (MERS-CoV) is an emerging zoonotic virus considered as one of the major public threat with a total number of 2 298 laboratory-confirmed cases and 811 associated deaths reported by World Health Organization as of January 2019. The transmission of the virus was expected to be from the camels found in Middle Eastern countries via the animal and human interaction. The genome structure provided information about the pathogenicity and associated virulent factors present in the virus. Recent studies suggested that there were limited insight available on the development of novel therapeutic strategies to induce immunity against the virus. The severities of MERS-CoV infection highlight the necessity of effective approaches for the development of various therapeutic remedies. Thus, the present review comprehensively and critically illustrates the recent aspects on the epidemiology of the virus, the structural and functional features of the viral genome, viral entry and transmission, major mechanisms of pathogenesis and associated virulent factors, current animal models, detection methods and novel strategies for the development of vaccines against MERS-CoV. The review further illustrates the molecular and computational virtual screening platforms which provide insights for the identification of putative drug targets and novel lead molecules toward the development of therapeutic remedies

Characteristics of the 8,977 Pregnant Women at Kaiser Permanente Northern California Who Delivered Between 2011 and 2013.

<p>Characteristics of the 8,977 Pregnant Women at Kaiser Permanente Northern California Who Delivered Between 2011 and 2013.</p

Odds ratios and 95% confidence intervals from multivariable* models of trimester-specific GWG and risk of SGA or LGA infants, by maternal pre-pregnancy BMI.

<p>*Adjusted for race/ethnicity, maternal age at delivery, gestational age at delivery, parity, pre-pregnancy BMI, gestational diabetes status, infant sex, pre-pregnancy physical activity (in tertiles of MET-minutes/week), pre-pregnancy Western dietary pattern score (in tertiles), and pre-pregnancy Prudent dietary pattern score (in tertiles); ** = indicates statistical significance (p-value <0.05).</p

Adjusted^a Odds Ratios (ORs) and 95% Confidence Intervals (CIs) for Size for Gestational Age Associated With Total and Trimester-Specific Gestational Weight Gain (GWG).

<p>Adjusted<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0159500#t002fn001" target="_blank">^a</a> Odds Ratios (ORs) and 95% Confidence Intervals (CIs) for Size for Gestational Age Associated With Total and Trimester-Specific Gestational Weight Gain (GWG).</p

A cohort study of maternal cardiometabolic risk factors and primary cesarean delivery in an integrated health system.

BACKGROUND:Maternal cardiometabolic risk factors (i.e., hyperglycemia, pre-existing hypertension and high body mass index) impact fetal growth and risk of having a cesarean delivery. However, the independent and joint contribution of maternal cardiometabolic risk factors to primary cesarean section is unclear. We aimed to elucidate the degree to which maternal cardiometabolic risk factors contribute to primary cesarean deliveries and whether associations vary by infant size at birth in an integrated health system. METHODS:A cohort study of 185,045 singleton livebirths from 2001 to 2010. Poisson regression with robust standard errors provided crude and adjusted relative risks (RR) and 95% confidence intervals (CIs) for cesarean delivery risk associated with risk factors. We then estimated the proportion of cesarean sections that could be prevented if the cardiometabolic risk factor in pregnant women were eliminated (the population-attributable risk [PAR]). RESULTS:In a single multivariable model, maternal cardiometabolic risk factors were independently associated with cesarean delivery: RR (95% CI) abnormal glucose screening 1.04 (1.01-1.08); gestational diabetes 1.18 (1.11-1.18) and pre-existing diabetes 1.60 (1.49-1.71); pre-existing hypertension 1.16 (1.10-1.23); overweight 1.27 (1.24-1.30); obese class I 1.46 (1.42-1.51); obese class II 1.73 (1.67-1.80); and obese class III 1.97 (1.88-2.07); adjusting for established risk factors, medical facility and year. The associations between maternal cardiometabolic risk factors and primary cesarean delivery remained among infants with appropriate weights for gestational age. The PARs were 17.4% for overweight/obesity, 7.0% for maternal hyperglycemia, 2.0% for pre-existing hypertension and 20.5% for any cardiometabolic risk factor. CONCLUSIONS:Maternal cardiometabolic risk factors were independently associated with risk of primary cesarean delivery, even among women delivering infants born at an appropriate size for gestational age. Effective strategies to increase the proportion of women entering pregnancy at an optimal weight with normal blood pressure and glucose before pregnancy could potentially eliminate up to 20% of cesarean deliveries

Low prepregnancy adiponectin concentrations are associated with a marked increase in risk for development of gestational diabetes mellitus.

ObjectiveTo examine whether circulating total and high-molecular weight (HMW) adiponectin concentrations, measured before pregnancy, are associated with subsequent risk of gestational diabetes mellitus (GDM).Research design and methodsThis was a nested case-control study among women who participated in the Kaiser Permanente Northern California Multiphasic Health Check-up exam (1984-1996) with a serum sample obtained and who had a subsequent pregnancy (1984-2009). Eligible women were free of recognized diabetes. Case subjects were the 256 women who developed GDM. Two control subjects were selected for each case and matched for year of blood draw, age at exam, age at pregnancy, and number of intervening pregnancies.ResultsCompared with the highest quartile of adiponectin, the risk of GDM increased with decreasing quartile (odds ratio [OR] 1.5 [95% CI 0.7-2.9], 3.7 [1.9-7.2], and 5.2 [2.6-10.1]; P(trend) &lt;0.001) after adjustment for family history of diabetes, BMI, parity, race/ethnicity, cigarette smoking, and glucose and insulin concentrations. Similar estimates were observed for HMW (P(trend) &lt;0.001). The combined effects of having total adiponectin levels below the median (&lt;10.29 mg/mL) and being overweight or obese (BMI ≥25.0 kg/m(2)) were associated with a sevenfold increased risk of GDM compared with normal-weight women with adiponectin levels above the median (OR 6.7 [95% CI 3.6-12.5]).ConclusionsPrepregnancy low adiponectin concentrations, a marker of decreased insulin sensitivity and altered adipocyte endocrine function, is associated with reduced glucose tolerance during pregnancy and may identify women at high risk for GDM to target for early intervention

Rates of malignancies among patients with moderate to severe atopic dermatitis: a retrospective cohort study

Objectives Patients with atopic dermatitis (AD), also known as eczema, may be at an increased risk for malignancies compared with patients without AD; however, incidence rates (IRs) of malignancies in patients with moderate to severe AD are largely unknown. The objective of this study was to evaluate and compare IRs of malignancies in adults with moderate to severe AD (aged ≥18 years).Design Retrospective cohort study using data from a Kaiser Permanente Northern California (KPNC) cohort. AD severity classification was adjudicated with medical chart review. Covariates and stratification variables included age, sex and smoking status.Setting Data were obtained from the KPNC healthcare delivery system in northern California, USA. Cases of AD were defined by outpatient dermatologist-rendered codes and prescriptions of topical therapy or phototherapy (moderate) or systemic treatment (severe).Participants KPNC health plan members with moderate or severe AD (2007–2018).Primary and secondary outcome measures Malignancy IRs and 95% CIs per 1000 person-years were calculated.Results 7050 KPNC health plan members with moderate and severe AD met eligibility criteria for inclusion. IRs (95% CI) were highest for non-melanoma skin cancer (NMSC) in patients with moderate and severe AD (4.6 (95% CI 3.9 to 5.5) and 5.9 (95% CI 3.8 to 9.2), respectively) and breast cancer (2.2 (95% CI 1.6 to 3.0) and 0.5 (95% CI 0.1 to 3.9), respectively). Except for breast cancer, which was only evaluated in women, malignancies were higher (with non-overlapping CIs) in patients with moderate and moderate to severe AD in men versus women for basal cell carcinoma and NMSC and in former versus never smokers for NMSC and squamous cell carcinoma.Conclusions This study estimated IRs of malignancies in patients with moderate and severe AD and provides valuable information for dermatology clinicians and ongoing clinical trials in these populations