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y syndrome coronavirus 2 infection did not disrupt neonatal Fc receptor expression in the placenta, maternal transfer of severe acute respiratory syndrome coronavirus 2 neutralizing antibody was inhibited by infection during pregnancy.
Severe acute respiratory syndrome coronavirus 2 infection during pregnancy was characterized by placental inflammation and reduced antiviral antibody responses, which may impact the efficacy of coronavirus disease 2019 treatment in pregnancy. In addition, the long-term implications of placental inflammation for neonatal health require greater consideration.
Severe acute respiratory syndrome coronavirus 2 infection during pregnancy was characterized by placental inflammation and reduced antiviral antibody responses, which may impact the efficacy of coronavirus disease 2019 treatment in pregnancy. In addition, the long-term implications of placental inflammation for neonatal health require greater consideration.
Black-serving hospitals are associated with increased maternal risk. However, prior administrative data research on maternal disparities has generally included limited hospital factors. More detailed evaluation of hospital factors related to obstetric outcomes may be important in understanding disparities.
To examine detailed characteristics of Black-serving hospitals and how these characteristics are associated with risk for severe maternal morbidity (SMM).
This serial cross-sectional study linked the 2010-2011 Nationwide Inpatient Sample and the 2013 American Hospital Association Annual Survey Databases. Delivery hospitalizations occurring to women 15-54 years of age were identified. SIS3 The proportions ofnon-Hispanic Black patients within a hospital was categorized intoquartiles, and hospital factors such as specialized medical, surgical and safety-net services as well as payer mix were compared across these quartiles. A series of models was performed evaluating risk for SMM with Black-serving hospital qving hospital quartile carried the lowest risk for SMM. However, SMM risks were similar across the 2
(aRR 1.31, 95% CI 1.08, 1.59), 3
(aRR 1.27, 95% 1.05, 1.55), and 4
(aRR 1.29, 95% CI 1.07, 1.55) quartiles.
Black-serving hospitals were more likely to provide a range of specialized medical, surgical, and safety-net services and to have a higher Medicaid burden. Payer mix and unmeasured confounding may account for some of the maternal risk associated with Black-serving hospitals.
Black-serving hospitals were more likely to provide a range of specialized medical, surgical, and safety-net services and to have a higher Medicaid burden. Payer mix and unmeasured confounding may account for some of the maternal risk associated with Black-serving hospitals.With the increase in throughput and sensitivity, biophysical technology has become a major component of the early drug discovery phase. Surface plasmon resonance technology (SPR) is one of the most widely used biophysical technologies. It has the advantages of circumventing labeling, molecular weight limitations, and neglect of low affinity interactions, etc., and provides a robust platform for hit to lead discovery and optimization. Here, we successfully established a reliable and repeatable tryptophanyl tRNA synthetase (TrpRS) SPR high-throughput screening and validation system by optimizing the TrpRS tag, TrpRS immobilization methodology, and the buffer conditions. When TrpRS was immobilized on Streptavidin (SA) sensor chip, the substrate competitive inhibitor indolmycin exhibited the best binding affinity in HBS-P (10 mM HEPES, 150 mM NaCl, 0.05% surfactant P-20, pH 7.4), 1 mM ATP and MgCl2, with a KD (dissociation equilibrium constant) value of 0.6 ± 0.1 μM. The Z-factor values determined in the screening assays were all larger than 0.9. We hope that our proposed research ideas and methods may provide a scientific basis for establishing SPR analysis of other drug targets, accelerate the discovery and optimization of target lead compounds, and assist the clinical application of next-generation drugs.Macrophages are multi-functional innate immune cells that occupy normal or pathologic tissues, including cancer tissues. link2 The importance of macrophage ontogeny and the transcriptional networks underlying their functional diversity are underappreciated in immuno-oncology. Here, we discuss the implications of these fundamental characteristics for therapeutically reprogramming macrophages to sustain their tumoricidal activities.Metastasis is facilitated by the formation of a “premetastatic niche,” which is fostered by primary tumor-derived factors. Colorectal cancer (CRC) metastasizes mainly to the liver. We show that the premetastatic niche in the liver is induced by bacteria dissemination from primary CRC. We report that tumor-resident bacteria Escherichia coli disrupt the gut vascular barrier (GVB), an anatomical structure controlling bacterial dissemination along the gut-liver axis, depending on the virulence regulator VirF. Upon GVB impairment, bacteria disseminate to the liver, boost the formation of a premetastatic niche, and favor the recruitment of metastatic cells. In training and validation cohorts of CRC patients, we find that the increased levels of PV-1, a marker of impaired GVB, is associated with liver bacteria dissemination and metachronous distant metastases. Thus, PV-1 is a prognostic marker for CRC distant recurrence and vascular impairment, leading to liver metastases.Serine metabolism promotes tumor oncogenesis and regulates immune cell functions, but whether it also contributes to antiviral innate immunity is unknown. Here, we demonstrate that virus-infected macrophages display decreased expression of serine synthesis pathway (SSP) enzymes. Suppressing the SSP key enzyme phosphoglycerate dehydrogenase (PHGDH) by genetic approaches or by treatment with the pharmaceutical inhibitor CBR-5884 and by exogenous serine restriction enhanced IFN-β-mediated antiviral innate immunity in vitro and in vivo. Mechanistic experiments showed that virus infection or serine metabolism deficiency increased the expression of the V-ATPase subunit ATP6V0d2 by inhibiting S-adenosyl methionine-dependent H3K27me3 occupancy at the promoter. ATP6V0d2 promoted YAP lysosomal degradation to relieve YAP-mediated blockade of the TBK1-IRF3 axis and, thus, enhance IFN-β production. These findings implicate critical functions of PHGDH and the key immunometabolite serine in blunting antiviral innate immunity and also suggest manipulation of serine metabolism as a therapeutic strategy against virus infection.
Becoming an oral-maxillofacial surgeon is often challenging for young trainees. The purpose of this manuscript is to explore how a student-led group, which emphasizes networking, mentorship, and academic opportunities, may impact one’s journey to becoming an oral-maxillofacial surgeon.
This was a cross-sectional descriptive study where a 5-question Likert-type survey was administered to students who matriculated into residency and participated in a student-led group called Passing The Scalpel (PTS). This survey evaluated the value of PTS in providing exposure, career decision-making, networking/mentorship, and camaraderie. The results were analyzed, and statistical outcomes were evaluated.
There was an 80.5% response rate (n=29). Question 1 regarding first exposure to oral-maxillofacial surgery had a mean score of 2.55 (standard deviation [SD]= 1.35; χ
=15.39; P<.05). Question 2 regarding choosing oral-maxillofacial surgery as a career had a mean score of 3.66 (SD= 1.11; χ
=10.84; P<.05). Question 3 regarding offering mentorship and networking had a mean score of 4.14 (SD= 0.92; χ
=27.81; P<.05). Question 4 regarding increasing applicant camaraderie had a mean score of 4.21 (SD= 0.77; χ
=36.71; P<.05). Question 5 regarding the importance of PTS within a dental curriculum had a score of 4.48 (SD= 0.68; χ
=41.89; P<.05).
PTS is an effective student-led initiative that emphasizes early exposure, networking, and mentorship opportunities and encourages students in choosing oral-maxillofacial surgery as a specialty. PTS demonstrates that student-led initiatives can fulfill unmet needs in the dental curriculum.
PTS is an effective student-led initiative that emphasizes early exposure, networking, and mentorship opportunities and encourages students in choosing oral-maxillofacial surgery as a specialty. PTS demonstrates that student-led initiatives can fulfill unmet needs in the dental curriculum.
Volanesorsen is an antisense oligonucleotide that targets hepatic apolipoprotein C-III synthesis and reduces plasma triglyceride concentration. The aim of this study was to explore the safety and efficacy of volanesorsen in patients with multifactorial chylomicronaemia syndrome.
The COMPASS trial was a randomised, placebo-controlled, double-blind, phase 3 study done at 38 international clinical sites in Canada, France, Germany, the Netherlands, UK, and USA. Eligible patients were aged 18 years or older with multifactorial severe hypertriglyceridaemia or familial chylomicronaemia syndrome, who had a BMI of 45 kg/m
or less and fasting plasma triglyceride of 500 mg/dL or higher. Patients were randomly assigned (21) with an interactive response system using an allocation sequence and permuted block randomisation to receive subcutaneous volanesorsen (300 mg) or a matched volume of placebo (1·5 mL) once a week for 26 weeks. After 13 weeks of treatment, dosing was changed to 300 mg of volanesorsen or placebo elyomicronaemia and might reduce acute pancreatitis events in these patients.
Ionis Pharmaceuticals and Akcea Therapeutics.
Ionis Pharmaceuticals and Akcea Therapeutics.
A 2017 meta-analysis of data from 25 randomised controlled trials (RCTs) of vitamin D supplementation for the prevention of acute respiratory infections (ARIs) revealed a protective effect of this intervention. We aimed to examine the link between vitamin D supplementation and prevention of ARIs in an updated meta-analysis.
For this systematic review and meta-analysis, we searched MEDLINE, Embase, the Cochrane Central Register of Controlled Trials, Web of Science, and the ClinicalTrials.gov registry for studies listed from database inception to May 1, 2020. Double-blind RCTs of vitamin D
, vitamin D
, or 25-hydroxyvitamin D (25[OH]D) supplementation for any duration, with a placebo or low-dose vitamin D control, were eligible if they had been approved by a research ethics committee, and if ARI incidence was collected prospectively and prespecified as an efficacy outcome. Studies reporting results of long-term follow-up of primary RCTs were excluded. link3 Aggregated study-level data, stratified by baseline 2500-1000 IU for up to 12 months, and age at enrolment of 1·00-15·99 years. The relevance of these findings to COVID-19 is not known and requires further investigation.
None.
None.
In patients with type 2 diabetes, hyperglycaemia is an independent risk factor for COVID-19-related mortality. Associations between pre-infection prescription for glucose-lowering drugs and COVID-19-related mortality in people with type 2 diabetes have been postulated but only investigated in small studies and limited to a few agents. We investigated whether there are associations between prescription of different classes of glucose-lowering drugs and risk of COVID-19-related mortality in people with type 2 diabetes.
This was a nationwide observational cohort study done with data from the National Diabetes Audit for people with type 2 diabetes and registered with a general practice in England since 2003. Cox regression was used to estimate the hazard ratio (HR) of COVID-19-related mortality in people prescribed each class of glucose-lowering drug, with covariate adjustment with a propensity score to address confounding by demographic, socioeconomic, and clinical factors.
Among the 2 851 465 people with type 2 diabetes included in our analyses, 13 479 (0·5%) COVID-19-related deaths occurred during the study period (Feb 16 to Aug 31, 2020), corresponding to a rate of 8·9 per 1000 person-years (95% CI 8·7-9·0).