Associations between physical activity, brain health, cognitive function, and circulating GPLD1 in healthy older (65-85 years) individuals.

Declines in physical and cognitive function are common in older adults. The circulating enzyme glycosylphosphatidylinositol (GPI)-specific phospholipase D1 (GPLD1) is elevated after exercise and has been associated with improved cognitive function when administered to aged mice. The purpose of this study was to investigate the relationship between GPLD1 and both cognitive function and brain structure/function in older adults with either high or low levels of physical activity.

Changes in insulin sensitivity and gut peptides 8 and 52 weeks after bariatric surgery or low-calorie diet.

The endocrine consequences of weight loss by bariatric surgery (BS) and caloric restriction are not fully understood but contribute to variable improvements in insulin sensitivity and cardiometabolic health. This study compared changes in insulin sensitivity and plasma concentrations of gut peptides 8 weeks and 1 year after BS and a low-calorie diet (LCD). Nineteen female patients with obesity self-selected BS (gastric bypass [n = 5] or sleeve gastrectomy [n = 7]) or LCD (n = 7) in this parallel-arm, prospective observational study.

Use of cardiopulmonary exercise testing to identify mechanisms of exertional symptoms in children with long COVID.

Background: Little is known about the mechanisms of exercise intolerance and exertional symptoms in children with long COVID. Through utilization of cardiopulmonary exercise testing (CPET), this study is the first of its kind to evaluate exertional symptoms and attempt to identify potential mechanism of long COVID-19 in children.

Objective: To determine if CPET will uncover potential reasons for persistent symptoms of long COVID when there is no indication of cardiopulmonary or upper airway disease.

Molecular Transducers of Physical Activity Consortium (MoTrPAC): human studies design and protocol.

Physical activity, including structured exercise, is associated with favorable health-related chronic disease outcomes. Although there is evidence of various molecular pathways that affect these responses, a comprehensive molecular map of these molecular responses to exercise has not been developed. The Molecular Transducers of Physical Activity Consortium (MoTrPAC) is a multicenter study designed to isolate the effects of structured exercise training on the molecular mechanisms underlying the health benefits of exercise and physical activity.

Effect of exercise training on insulin-stimulated glucose disposal: a systematic review and meta-analysis of randomized controlled trials.

Background And Objective: The effect of exercise training on whole-body insulin sensitivity has not been systematically summarized. We aimed to summarize the data from randomized controlled trials evaluating the effect of exercise training on insulin action, in adults.

Subjects: MEDLINE, EMBASE, and CENTRAL databases were searched until January 2021.

What Primary Care Practitioners Need to Know about the New NICE Guideline for Myalgic Encephalomyelitis/Chronic Fatigue Syndrome in Adults.

The new NICE guideline for myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), published in October 2021, makes significant changes in treatment recommendations. It acknowledges the complexity of this chronic medical condition, which always impacts quality of life and can be profoundly disabling, recognising the prejudice and stigma that people with ME/CFS often experience in the absence of any specific diagnostic test. The guideline outlines steps for accurate diagnosis, recognising post-exertional malaise as a core symptom; importantly, ME/CFS can now be diagnosed after just 3 months in a bid to improve long-term health outcomes.

Risk Factors for Nontuberculous Mycobacteria Infections in Solid Organ Transplant Recipients: A Multinational Case-Control Study.

Background: Risk factors for nontuberculous mycobacteria (NTM) infections after solid organ transplant (SOT) are not well characterized. Here we aimed to describe these factors.

Methods: Retrospective, multinational, 1:2 matched case-control study that included SOT recipients ≥12 years old diagnosed with NTM infection from 1 January 2008 to 31 December 2018.

Effects of Field Position on Fluid Balance and Electrolyte Losses in Collegiate Women's Soccer Players.

Research investigating hydration strategies specialized for women's soccer players is limited, despite the growth in the sport. The purpose of this study was to determine the effects of fluid balance and electrolyte losses in collegiate women's soccer players. Eighteen NCAA Division I women's soccer players were recruited (age: 19.

Multiple Fatalities in a Family Cluster of COVID-19 With Acute Respiratory Distress Syndrome.

Cases of COVID-19 family clusters have been reported across the globe. While disease severity can vary widely, reports of severe infection leading to multiple fatalities within a family are limited. Four family members each presented to the emergency department with fever and upper respiratory symptoms.

COVID-19: Initial Perioperative and Perianesthesia Nursing Response in a Military Medical Center.

Nurses have historically led efforts to improve the health of populations while simultaneously and unselfishly providing care during pivotal moments of national need. The COVID-19 pandemic has placed an unprecedented strain on the US health care system, including severe shortages of hospital beds, supplies, equipment, pharmaceuticals, and healthy frontline clinicians. Perioperative and perianesthesia leaders and clinicians have unique opportunities to provide patient care during the COVID-19 crisis.

Haplotyping germline and cancer genomes with high-throughput linked-read sequencing.

Haplotyping of human chromosomes is a prerequisite for cataloguing the full repertoire of genetic variation. We present a microfluidics-based, linked-read sequencing technology that can phase and haplotype germline and cancer genomes using nanograms of input DNA. This high-throughput platform prepares barcoded libraries for short-read sequencing and computationally reconstructs long-range haplotype and structural variant information.

Multiplexed target detection using DNA-binding dye chemistry in droplet digital PCR.

Two years ago, we described the first droplet digital PCR (ddPCR) system aimed at empowering all researchers with a tool that removes the substantial uncertainties associated with using the analogue standard, quantitative real-time PCR (qPCR). This system enabled TaqMan hydrolysis probe-based assays for the absolute quantification of nucleic acids. Due to significant advancements in droplet chemistry and buoyed by the multiple benefits associated with dye-based target detection, we have created a "second generation" ddPCR system compatible with both TaqMan-probe and DNA-binding dye detection chemistries.

Process development and production of cGMP grade Melan-A for cancer vaccine clinical trials.

Melan-A is a cancer testis antigen commonly found in melanoma, and has been shown to stimulate the body's immune response against cancerous cells. We have developed and executed a process utilizing current good manufacturing practices (cGMP) to produce the 6 times-His tagged protein in C41DE3 Escherichia coli for use in Phase I clinical trials. Approximately 11 g of purified Melan-A were produced from a 20 L fed-batch fermentation.

Conformationally preorganised hosts for anions using norbornane and fused [n]polynorbornane frameworks.

Norbornane and fused [n]polynorbornane frameworks are readily synthesised, can be tailored to a variety of predictable geometries and can be functionalised regiospecifically. As such, these highly preorganised scaffolds offer the supramolecular chemist an excellent starting point when designing hosts for specific guests. This feature article will highlight the evolution of our research from relatively simple norbornane based anion receptors to more sophisticated tetrathioureido functionalised fused [n]polynorbornane hosts.

Examples of regioselective anion recognition among a family of two-, three-, and four-"armed" bis-, tris-, and tetrakis(thioureido) [n]polynorbornane hosts.

A family of conformationally preorganized, [n]polynorbornane-based anion hosts 1a,b-6a,b have been synthesized. The series includes receptors with 4, 8, and 12 H-bond donors. Using (1)H NMR titration techniques, evaluation of the new hosts against a series of alkyl and aryl dicarboxylates as well as a range of phosphoanionic species has revealed that the tris(thioureido) hosts (in particular 3a) are capable of regioselectively binding dicarboxylates and pyrophosphate (H(2)PPi(2-)).

Methods for chromatographic removal of endotoxin.

Endotoxin removal is critical when producing therapeutic proteins in bacterial systems. This hydrophobic compound can be removed through chromatography or filtration, but presents unique challenges dependent upon protein composition as well as production scale. Here we present a robust method for endotoxin removal at the pilot production scale using fast protein liquid chromatography and buffers specifically engineered for endotoxin removal.

Expression and purification of cGMP grade NY-ESO-1 for clinical trials.

NY-ESO-1 is a cancer testis antigen expressed in numerous cancers. Initial tests have shown its efficacy as a cancer vaccine, stimulating the body's own immune response against the invading tumor. To produce enough material for phase I clinical trials, a process using current good manufacturing practices to produce clinical grade material was developed and executed.

Multiplex single nucleotide polymorphism genotyping utilizing ligase detection reaction coupled surface enhanced Raman spectroscopy.

Single nucleotide polymorphisms (SNPs) are one of the key diagnostic markers for genetic disease, cancer progression, and pharmcogenomics. The ligase detection reaction (LDR) is an excellent method to identify SNPs, combining low detection limits and high specificity. We present the first multiplex LDR-surface enhanced Raman spectroscopy (SERS) SNP genotyping scheme.

Recombinant immunotherapeutics: current state and perspectives regarding the feasibility and market.

Recombinant immunotherapeutics are important biologics for the treatment and prevention of various diseases. Immunotherapy can be divided into two categories, passive and active. For passive immunotherapy, the successes of antibody and cytokine therapeutics represent a promising future and opportunities for improvements.

Binding of the terephthalate dianion by di- tri- and tetrathiourea functionalised fused [3] and [5]polynorbornane based hosts.

The affinity of new di-, tri- and tetrathiourea functionalised fused [3] and [5]polynorbornane based hosts 1-6 towards terephthalate2- was proportional to the size of the preorganised cleft/cavity imparted by the polynorbornane scaffold. Receptors based on the [5]polynobornane framework had greater affinities for the anion due to a higher degree of host:guest size complementarity. Hosts 1-5 formed 1:1 host:guest complexes with the rigid dianion, yet remarkably, host 6 was found to bind two terephthalate guests.

Surface-enhanced Raman scattering based ligase detection reaction.

Genomics provides a comprehensive view of the complete genetic makeup of an organism. Individual sequence variations, as manifested by single nucleotide polymorphisms (SNPs), can provide insight into the basis for a large number of phenotypes and diseases including cancer. The ability rapidly screen for SNPs will have a profound impact on a number of applications, most notably personalized medicine.

Size matters--strong binding of the terephthalate dianion by thiourea functionalised fused [n]polynorbornane hosts.

Remarkably strong binding of the new [5]polynorbornane based host to the terephthalate dianion is based on size complementarity of the preorganised binding cleft with the rigid dicarboxylate guest.