A 3D in vitro model of the dermoepidermal junction amenable to mechanical testing.

Recessive dystrophic Epidermolysis Bullosa (RDEB) is caused by mutations in collagen-type VII gene critical for the dermoepidermal junction (DEJ) formation. Neither tissues of animal models nor currently available in vitro models are amenable to the quantitative assessment of mechanical adhesion between dermal and epidermal layers. Here, we created a 3D in vitro DEJ model using extracellular matrix (ECM) proteins of the DEJ anchored to a poly(ethylene glycol)-based slab (termed ECM composites) and seeded with human keratinocytes and dermal fibroblasts.

Post-Infectious Functional Gastrointestinal Disorders Among Populations Living in Areas of High Enteric Infection Risk: Adding Some Clarity or Further Muddying the Waters.

Post-infectious functional gastrointestinal disorders (FGID) are a relatively well-studied phenomenon among individuals who are resident in temperate and higher-income regions around the world. Less is known about the risk of FGID among residents in tropical and hyperendemic settings where acute gastroenteritis risk and exposure is high. This editorial summarizes the primary results from a recently published study focusing on this unique clinical scenario and considers the interpretation of the data as well as highlights additional research needs.

Comparison of stool collection and storage on Whatman FTA Elute cards versus frozen stool for enteropathogen detection using the TaqMan Array Card PCR assay.

The use of Polymerase Chain Reaction (PCR) assays for pathogen detection in travelers' diarrhea (TD) field studies is limited by the on-site processing and storage requirements for fecal specimens. The objectives of this investigation were to i) characterize the pathogen distribution in deployed military personnel with TD using the TaqMan® Array Card PCR (TAC) on frozen stool and diarrheal smears on Whatman FTA Elute cards (FTA cards), and to ii) compare TAC detection of enteropathogen targets using smeared FTA cards and frozen stool, using TAC on frozen stool as the 'reference standard'. Stool samples, obtained from active duty personnel with acute TD enrolled in a field trial, were smeared onto FTA cards and stored at room temperature.

A post-hoc pooled analysis to evaluate the risk of hypoglycaemia with insulin glargine 300 U/mL (Gla-300) versus 100 U/mL (Gla-100) over wider nocturnal windows in individuals with type 2 diabetes on a basal-only insulin regimen.

The EDITION trials in type 2 diabetes demonstrated comparable glycaemic control with less nocturnal and anytime (24-hour) hypoglycaemia for insulin glargine 300 U/mL (Gla-300) versus glargine 100 U/mL (Gla-100). However, the predefined nocturnal window (0:00-5:59 AM) may not be the most relevant for clinical practice. This post-hoc analysis compared expansions of the predefined nocturnal interval during basal insulin treatment without prandial insulin.

Enterotoxigenic virulence gene regulation in human infections.

Enterotoxigenic (ETEC) is a global diarrheal pathogen that utilizes adhesins and secreted enterotoxins to cause disease in mammalian hosts. Decades of research on virulence factor regulation in ETEC has revealed a variety of environmental factors that influence gene expression, including bile, pH, bicarbonate, osmolarity, and glucose. However, other hallmarks of the intestinal tract, such as low oxygen availability, have not been examined.

Rotavirus Vaccination and the Global Burden of Rotavirus Diarrhea Among Children Younger Than 5 Years.

Importance: Rotavirus infection is the global leading cause of diarrhea-associated morbidity and mortality among children younger than 5 years.

Objectives: To examine the extent of rotavirus infection among children younger than 5 years by country and the number of deaths averted because of the rotavirus vaccine.

Design, Setting, And Participants: This report builds on findings from the Global Burden of Disease Study 2016, a cross-sectional study that measured diarrheal diseases and their etiologic agents.

Update on vaccines for enteric pathogens.

Background: Acute diarrhoeal disease caused by viral, bacterial and parasitic infections is a major global health problem; in low- and middle-income countries (LMICs) it is associated with substantial mortality and morbidity in children under 5. Some of these infections also impact large segments of populations in high-income countries (HICs), as well as individuals who travel overseas for work, business or pleasure.

Aims: The aim of this review is to describe the current landscape of licensed enteric vaccines, potential new vaccines on the horizon, and the challenges of development and utilization of vaccines against enteric pathogens.

Posterior Shoulder Dislocation During Morning PT: A Case Report.

Posterior shoulder dislocation should be considered in the differential diagnosis of acute shoulder pain and immobility following trauma. Although far less common then the anterior dislocation, it is associated with high rates of comorbidity. Seventy-nine percent of posterior shoulder dislocations are missed on initial presentation, which is partially responsible for the high rate of comorbidity associated with these injuries.

Glycaemic control, hypoglycaemia, and weight change with insulin glargine 300 U/mL versus insulin glargine 100 U/mL in Japanese adults with type 2 diabetes: A 12-month comparison by concomitant sulphonylurea and/or glinide use.

Aim: To explore if clinical effects and hypoglycaemia risks associated with insulin glargine 300 U/mL (Gla-300) and 100 U/mL (Gla-100) differed by sulphonylurea and/or glinide (SU/G) treatment.

Methods: A post hoc subgroup analysis of 12-month treatment data from the EDITION Japan 2 trial, a randomized, open-label, phase 3 study of Japanese people with type 2 diabetes receiving once-daily Gla-300/Gla-100 + oral antihyperglycaemic drugs. Participants previously receiving SU/G (+SU/G) were compared with those not taking SU/G (-SU/G).

Morphogenesis and motility of the Astyanax mexicanus gastrointestinal tract.

Through the course of evolution, the gastrointestinal (GI) tract has been modified to maximize nutrient absorption, forming specialized segments that are morphologically and functionally distinct. Here we show that the GI tract of the Mexican tetra, Astyanax mexicanus, has distinct regions, exhibiting differences in morphology, motility, and absorption. We found that A.

Phosphorus Leaching from an Organic and a Mineral Arable Soil in a Rainfall Simulation Study.

Phosphorus derived from agricultural systems has been found to cause eutrophication of surface waters. To combat this, the specific location of soil profile P release is necessary for development of effective mitigation strategies. This paper describes a P leaching study of two Swedish arable soils, an organic (Typic Haplosaprist) and a mineral soil (Typic Hapludalf), both with high P content.

Acid Suspends the Circadian Clock in Hypoxia through Inhibition of mTOR.

Recent reports indicate that hypoxia influences the circadian clock through the transcriptional activities of hypoxia-inducible factors (HIFs) at clock genes. Unexpectedly, we uncover a profound disruption of the circadian clock and diurnal transcriptome when hypoxic cells are permitted to acidify to recapitulate the tumor microenvironment. Buffering against acidification or inhibiting lactic acid production fully rescues circadian oscillation.

NIH research opportunities for the prevention and treatment for chronic conditions.

Chronic conditions constitute the leading cause of death and disability in the USA and constitute 86 per cent of the nation's annual healthcare expenses. Approximately half of all American adults have at least one chronic condition; 25 per cent of these Americans have two or more chronic conditions. The National Institutes of Health have funded many projects that explain epidemiology, risk factors, and prevention and treatment of chronic conditions, though research questions remain.

"Guidewire Intravenous Catheter Systems Do Not Improve First-Pass Success Rates for Peripheral Access When Placed By Army Combat Medics (68W) in a Pre-hospital Setting." A Prospective, Randomized Controlled Trial with Crossover Study Design.

Introduction: This study was completed to determine if guidewire catheters improve first-pass success and time of placement for peripheral intravenous access. In the military, 21% of casualties from the battlefield arrive to a medical facility in hemorrhagic shock. The importance of successful and timely intravenous placement is crucial in the initial steps of preventing this condition.

Enterotoxigenic Escherichia coli-blood group A interactions intensify diarrheal severity.

Enterotoxigenic Escherichia coli (ETEC) infections are highly prevalent in developing countries, where clinical presentations range from asymptomatic colonization to severe cholera-like illness. The molecular basis for these varied presentations, which may involve strain-specific virulence features as well as host factors, has not been elucidated. We demonstrate that, when challenged with ETEC strain H10407, originally isolated from a case of cholera-like illness, blood group A human volunteers developed severe diarrhea more frequently than individuals from other blood groups.

Predictors of recurrence in remitted late-life depression.

Background: Late-life depression (LLD) is associated with a fragile antidepressant response and high recurrence risk. This study examined what measures predict recurrence in remitted LLD.

Methods: Individuals of age 60 years or older with a Diagnostic and Statistical Manual - IV (DSM-IV) diagnosis of major depressive disorder were enrolled in the neurocognitive outcomes of depression in the elderly study.

Human CD19-Targeted Mouse T Cells Induce B Cell Aplasia and Toxicity in Human CD19 Transgenic Mice.

The clinical success of chimeric antigen receptor (CAR) T cell therapy for CD19 B cell malignancies can be limited by acute toxicities and immunoglobulin replacement needs due to B cell aplasia from persistent CAR T cells. Life-threatening complications include cytokine release syndrome and neurologic adverse events, the exact etiologies of which are unclear. To elucidate the underlying toxicity mechanisms and test potentially safer CAR T cells, we developed a mouse model in which human CD19 (hCD19)-specific mouse CAR T cells were adoptively transferred into mice whose normal B cells express a hCD19 transgene at hemizygous levels.