The potential economic value of a therapeutic Chagas disease vaccine for pregnant women to prevent congenital transmission.

Background: Currently, there are no solutions to prevent congenital transmission of Chagas disease during pregnancy, which affects 1-40% of pregnant women in Latin America and is associated with a 5% transmission risk. With therapeutic vaccines under development, now is the right time to determine the economic value of such a vaccine to prevent congenital transmission.

Methods: We developed a computational decision model that represented the clinical outcomes and diagnostic testing strategies for an infant born to a Chagas-positive woman in Mexico and evaluated the impact of vaccination.

The global variation of medical student engagement in teaching: Implications for medical electives.

Introduction: International medical electives, whereby undergraduates visit an institution in a country other than their own, are a common part of medical training. Visiting students are often asked to provide local teaching, which may be acceptable where the visitor is acting within the bounds of their own competency and the normal practices of both their home and host institutions. However, the extent to which teaching is an accepted student activity globally has not previously been described.

Daratumumab plus lenalidomide and dexamethasone in relapsed/refractory multiple myeloma: extended follow-up of POLLUX, a randomized, open-label, phase 3 study.

In POLLUX, daratumumab (D) plus lenalidomide/dexamethasone (Rd) reduced the risk of disease progression or death by 63% and increased the overall response rate (ORR) versus Rd in relapsed/refractory multiple myeloma (RRMM). Updated efficacy and safety after >3 years of follow-up are presented. Patients (N = 569) with ≥1 prior line received Rd (lenalidomide, 25 mg, on Days 1-21 of each 28-day cycle; dexamethasone, 40 mg, weekly) ± daratumumab at the approved dosing schedule.

Impact of Aortic Arch Anatomy on Technical Performance and Clinical Outcomes in Patients with Acute Ischemic Stroke.

Background And Purpose: Arterial access is a technical consideration of mechanical thrombectomy that may affect procedural time, but few studies exist detailing the relationship of anatomy to procedural times and patient outcomes. We sought to investigate the respective impact of aortic arch and carotid artery anatomy on endovascular procedural times in patients with large-vessel occlusion.

Materials And Methods: We retrospectively reviewed imaging and medical records of 207 patients from 2 academic institutions who underwent mechanical thrombectomy for anterior circulation large-vessel occlusion from January 2015 to July 2018.

A Randomized Trial of Erythropoietin for Neuroprotection in Preterm Infants.

Background: High-dose erythropoietin has been shown to have a neuroprotective effect in preclinical models of neonatal brain injury, and phase 2 trials have suggested possible efficacy; however, the benefits and safety of this therapy in extremely preterm infants have not been established.

Methods: In this multicenter, randomized, double-blind trial of high-dose erythropoietin, we assigned 941 infants who were born at 24 weeks 0 days to 27 weeks 6 days of gestation to receive erythropoietin or placebo within 24 hours after birth. Erythropoietin was administered intravenously at a dose of 1000 U per kilogram of body weight every 48 hours for a total of six doses, followed by a maintenance dose of 400 U per kilogram three times per week by subcutaneous injection through 32 completed weeks of postmenstrual age.

Hybrid AlO-CHNHPbI Perovskites towards Avoiding Toxic Solvents.

We report the synthesis of organometal halide perovskites by milling CHNHI and PbI directly with an AlO scaffold to create hybrid AlO-CHNHPbI perovskites, without the use of organic capping ligands that otherwise limit the growth of the material in the three dimensions. Not only does this improve the ambient stability of perovskites in air (100 min versus 5 min for dimethylformamide (DMF)-processed material), the method also uses much fewer toxic solvents (terpineol versus dimethylformamide). This has been achieved by solid-state reaction of the perovskite precursors to produce larger perovskite nanoparticles.

Role of angiopoietin-like protein 3 in sugar-induced dyslipidemia in rhesus macaques: suppression by fish oil or RNAi.

Angiopoietin-like protein 3 (ANGPTL3) inhibits lipid clearance and is a promising target for managing cardiovascular disease. Here we investigated the effects of a high-sugar (high-fructose) diet on circulating ANGPTL3 concentrations in rhesus macaques. Plasma ANGPTL3 concentrations increased ∼30% to 40% after 1 and 3 months of a high-fructose diet (both < 0.

Association between IQ and FMR1 protein (FMRP) across the spectrum of CGG repeat expansions.

Fragile X syndrome, the leading heritable form of intellectual disability, is caused by hypermethylation and transcriptional silencing of large (CGG) repeat expansions (> 200 repeats) in the 5' untranslated region of the fragile X mental retardation 1 (FMR1) gene. As a consequence of FMR1 gene silencing, there is little or no production of FMR1 protein (FMRP), an important element in normal synaptic function. Although the absence of FMRP has long been known to be responsible for the cognitive impairment in fragile X syndrome, the relationship between FMRP level and cognitive ability (IQ) is only imprecisely understood.

Prophylactic antibiotics for penetrating abdominal trauma: duration of use and antibiotic choice.

Background: Penetrating abdominal trauma (PAT) is a common type of trauma leading to admission to hospital, which often progresses to septic complications. Antibiotics are commonly administered as prophylaxis prior to laparotomy for PAT. However, an earlier Cochrane Review intending to compare antibiotics with placebo identified no relevant randomised controlled trials (RCTs).

Long-read sequencing reveals the complex splicing profile of the psychiatric risk gene CACNA1C in human brain.

RNA splicing is a key mechanism linking genetic variation with psychiatric disorders. Splicing profiles are particularly diverse in brain and difficult to accurately identify and quantify. We developed a new approach to address this challenge, combining long-range PCR and nanopore sequencing with a novel bioinformatics pipeline.

Loneliness and Life Satisfaction Explained by Public-Space Use and Mobility Patterns.

Previous research has shown that personal, neighborhood, and mobility characteristics could influence life satisfaction and loneliness of people and that exposure to public spaces, such as green spaces, may also affect the extent to which people feel lonely or satisfied with life. However, previous studies mainly focused on one of these effects, resulting in a lack of knowledge about the simultaneous effects of these characteristics on loneliness and life satisfaction. This study therefore aims to gain insights into how public-space use mediates the relations between personal, neighborhood, and mobility characteristics on the one hand and loneliness and life satisfaction on the other hand.

The rise or fall of neglected tropical diseases in East Asia Pacific.

While the East Asia Pacific (EAP) region has experienced tremendous economic growth and development, the resulting public health gains from reductions in its neglected tropical diseases (NTDs) have been less than expected due to opposing forces of urbanization, political instability, food insecurity, and climate change, together with co-morbidities with non-communicable diseases, including diabetes and hypertension. To be sure there's been progress towards the elimination of lymphatic filariasis and trachoma through mass drug administration, and there are opportunities to extend MDA to yaws and scabies, but for most of the other NTDs we'll require new biotechnologies. So far, EAP's major technology hubs in China, Japan, Malaysia, Singapore, South Korea, and Taiwan have mostly failed to shift their attention towards new innovations for the NTDs, including new drugs, diagnostics, and vaccines, and vector control.

Gray Correlation Analysis and Prediction on Permanent Deformation of Subgrade Filled with Construction and Demolition Materials.

Construction and demolition (C&D) materials obtained from the demolition of buildings are proven to be qualified and sustainable subgrade fillers. The permanent deformation response of subgrade C&D materials under different moisture contents, degrees of compaction, deviator stresses, and confining pressures was revealed by carrying out dynamic triaxial texts. Then, using a four-factor and three-level orthogonal test and by calculating the Gray correlation degree of each factor, the influence degree of each factor on the permanent deformation was determined.

A phase 1 study of the safety, reactogenicity, and immunogenicity of a Schistosoma mansoni vaccine with or without glucopyranosyl lipid A aqueous formulation (GLA-AF) in healthy adults from a non-endemic area.

Background: Schistosomiasis caused by Schistosoma mansoni (Sm) is a chronic, debilitating and potentially deadly neglected tropical disease. The licensure of a vaccine to prevent schistosomiasis would represent a major breakthrough in public health.

Methods: The safety and immunogenicity of a candidate Sm vaccine were assessed in this phase I, double-blind, dose-escalation trial.

NKT Cells Coexpressing a GD2-Specific Chimeric Antigen Receptor and IL15 Show Enhanced Persistence and Antitumor Activity against Neuroblastoma.

Purpose: Vα24-invariant natural killer T cells (NKT) are attractive carriers for chimeric antigen receptors (CAR) due to their inherent antitumor properties and preferential localization to tumor sites. However, limited persistence of CAR-NKTs in tumor-bearing mice is associated with tumor recurrence. Here, we evaluated whether coexpression of the NKT homeostatic cytokine IL15 with a CAR enhances the persistence and therapeutic efficacy of CAR-NKTs.

The pipeline of antiviral T-cell therapy: what's in the clinic and undergoing development.

Virus-specific T cells allow targeting of multiple pathogens in patients after hematopoietic stem cell transplantation and have demonstrated potential efficacy for cytomegalovirus, Epstein-Barr Virus, and adenovirus. Novel targets may include BK virus, JC virus, varicella zoster virus, human herpesvirus 6, Aspergillus, human parainfluenza virus-3, herpes simplex virus Type I, Zika virus, and mycobacteria. Generation of patient-specific products and third-party products may expand feasibility of therapy.

Academic neurosurgery in the UK: present and future directions.

Academic neurosurgery encompasses basic science and clinical research efforts to better understand and treat diseases of relevance to neurosurgical practice, with the overall aim of improving treatment and outcome for patients. In this article, we provide an overview of the current and future directions of British academic neurosurgery. Training pathways are considered together with personal accounts of experiences of structured integrated clinical academic training and unstructured academic training.

Observational designs in clinical multiple sclerosis research: Particulars, practices and potentialities.

Observational studies investigate a wide range of topics in multiple sclerosis research. This paper presents an overview of the various observational designs and their applications in clinical studies. Observational studies are well suited for making discoveries and assessing new explanations of phenomena, but less so for establishing causal relationships, due to confounding by indication (selection bias), co-morbidity, socio-economic or other factors.

The Pharmacokinetics and Relative Bioavailability of Mepolizumab 100 mg Liquid Formulation Administered Subcutaneously to Healthy Participants: A Randomized Trial.

This study compared the pharmacokinetic (PK) profile of a new liquid formulation of mepolizumab with the established lyophilized formulation. In this open-label, parallel-group, single-dose study (NCT03014674; GSK ID: 204958), healthy participants were randomized (1:1:1) to receive a single mepolizumab dose (100 mg) administered subcutaneously as liquid in a single-use prefilled syringe or single-use prefilled autoinjector, or as a lyophilized formulation. Maximum plasma concentration, area under the plasma concentration-time curve from time zero (predose) to time of last quantifiable concentration (AUC ), and AUC from time zero to infinity (AUC ) as well as additional PK parameters, safety assessments, and blood eosinophil count were evaluated.

Ileal interposition surgery targets the hepatic TGF-β pathway, influencing gluconeogenesis and mitochondrial bioenergetics in the UCD-T2DM rat model of diabetes.

Ileal interposition (IT) is a surgical procedure that increases the delivery of incompletely digested nutrients and biliary and pancreatic secretions to the distal intestinal mucosa. Here, we investigated the metabolic impact of this intervention in 2-mo-old prediabetic University of California, Davis type 2 diabetes mellitus rats by assessing liver gene expression at 1.5 mo post-IT surgery.

Safety and feasibility of virus-specific T cells derived from umbilical cord blood in cord blood transplant recipients.

Adoptive transfer of virus-specific T cells (VSTs) has been shown to be safe and effective in stem cell transplant recipients. However, the lack of virus-experienced T cells in donor cord blood (CB) has prevented the development of ex vivo expanded donor-derived VSTs for recipients of this stem cell source. Here we evaluated the feasibility and safety of ex vivo expansion of CB T cells from the 20% fraction of the CB unit in pediatric patients receiving a single CB transplant (CBT).

TGF-β1-p53 cooperativity regulates a profibrotic genomic program in the kidney: molecular mechanisms and clinical implications.

Chronic kidney disease affects >15% of the U.S. population and >850 million individuals worldwide.