Rational design and testing of new urease inhibitors to prevent urinary catheter blockage.

Catheter associated urinary tract infections (CAUTI) caused by urease-positive organisms can lead to catheter blockage: urease metabolizes urea in urine to ammonia causing an increase in pH and hence precipitation of struvite and apatite salts into the catheter lumen and bladder leading to blockage. Acetohydroxamic acid (AHA) is the only urease inhibitor currently approved for patient use, however, it is rarely used owing to its side effects. Here, we report the identification and development of new urease inhibitors discovered using a rational drug design approach.

Steps Toward Recapitulating Endothelium: A Perspective on the Next Generation of Hemocompatible Coatings.

Endothelium, the lining in this blood vessel, orchestrates three main critical functions such as protecting blood components, modulating of hemostasis by secreting various inhibitors, and directing clot digestion (fibrinolysis) by activating tissue plasminogen activator. No other surface can perform these tasks; thus, the contact of blood and blood-contacting medical devices inevitably leads to the activation of coagulation, often causing device failure, and thromboembolic complications. This perspective, first, discusses the biological mechanisms of activation of coagulation and highlights the efforts of advanced coatings to recapitulate one characteristic of endothelium, hereafter single functions of endothelium and noting necessity of the synergistic integration of its three main functions.

Analysis-ready VCF at Biobank scale using Zarr.

Background: Variant Call Format (VCF) is the standard file format for interchanging genetic variation data and associated quality control metrics. The usual row-wise encoding of the VCF data model (either as text or packed binary) emphasises efficient retrieval of all data for a given variant, but accessing data on a field or sample basis is inefficient. Biobank scale datasets currently available consist of hundreds of thousands of whole genomes and hundreds of terabytes of compressed VCF.

Serum AZD7442 (tixagevimab-cilgavimab) concentrations and IC values predict SARS-CoV-2 neutralising antibody titres.

Objectives: The evolution of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) necessitates rapid methods for assessing monoclonal antibody (mAb) potency against emerging variants. Authentic virus neutralisation assays are considered the gold standard for measuring virus-neutralising antibody (nAb) titres in serum. However, authentic virus-based assays pose inherent practical challenges for measuring nAb titres against emerging SARS-CoV-2 variants (e.

Estimating vaccine efficacy during open-label follow-up of COVID-19 vaccine trials based on population-level surveillance data.

While rapid development and roll out of COVID-19 vaccines is necessary in a pandemic, the process limits the ability of clinical trials to assess longer-term vaccine efficacy. We leveraged COVID-19 surveillance data in the U.S.

Prediction of cardiovascular risk factors from retinal fundus photographs: Validation of a deep learning algorithm in a prospective non-interventional study in Kenya.

Aim: Hypertension and diabetes mellitus (DM) are major causes of morbidity and mortality, with growing burdens in low-income countries where they are underdiagnosed and undertreated. Advances in machine learning may provide opportunities to enhance diagnostics in settings with limited medical infrastructure.

Materials And Methods: A non-interventional study was conducted to develop and validate a machine learning algorithm to estimate cardiovascular clinical and laboratory parameters.

Imaging of Light-Enhanced Extracellular Vesicle-Mediated Delivery of Oxaliplatin to Colorectal Cancer Cells via Laser Ablation, Inductively Coupled Plasma Mass Spectrometry.

Extracellular vesicles (EVs) are lipid bilayer structures released by all cells that mediate cell-to-cell communication via the transfer of bioactive cargo. Because of the natural origin of EVs, their efficient uptake by recipient cells, capacity to stabilize and transport biomolecules and their potential for cell/tissue targeting and preferential uptake by cancer cells, they have enormous potential for bioengineering into improved and targeted drug delivery systems. In this work, we investigated the use of laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS) as a tool to measure the loading of platinum-based chemotherapeutic agents.

Expert consensus guidance on respiratory physiotherapy and rehabilitation of patients with rib fractures: An international, multidisciplinary e-Delphi study.

Background: There is limited research supporting optimal respiratory physiotherapy or physical rehabilitation strategies for patients with rib fractures. The aim of this study was to develop key recommendations for the physiotherapy management of patients with rib fractures.

Methods: A three-round modified e-Delphi survey design, using an international Delphi panel including physiotherapy clinicians, researchers and lecturers, physician associates, trauma surgeons, and intensivists, was used in this study.

Less Is More: A Multimodal Pain Management Strategy Is Associated With Reduced Opioid Use in Hospitalized Trauma Patients.

Introduction: Adequate pain control is critical to the management and recovery of acutely injured patients. Opioids are associated with various adverse effects, and drug overdose is the leading cause of injury-related death in the United States. We hypothesized that a multimodal pain management protocol would reduce opioid use while still optimizing pain control.

Multiple hominin dispersals into Southwest Asia over the past 400,000 years.

Pleistocene hominin dispersals out of, and back into, Africa necessarily involved traversing the diverse and often challenging environments of Southwest Asia. Archaeological and palaeontological records from the Levantine woodland zone document major biological and cultural shifts, such as alternating occupations by Homo sapiens and Neanderthals. However, Late Quaternary cultural, biological and environmental records from the vast arid zone that constitutes most of Southwest Asia remain scarce, limiting regional-scale insights into changes in hominin demography and behaviour.

The expansion of Acheulean hominins into the Nefud Desert of Arabia.

The Arabian Peninsula is a critical geographic landmass situated between Africa and the rest of Eurasia. Climatic shifts across the Pleistocene periodically produced wetter conditions in Arabia, dramatically altering the spatial distribution of hominins both within and between continents. This is particularly true of Acheulean hominins, who appear to have been more tethered to water sources than Middle Palaeolithic hominins.

The pitfalls and virtues of population genetic summary statistics: Detecting selective sweeps in recent divergences.

During evolution, genomes are shaped by a plethora of forces that can leave characteristic signatures. A common goal when studying diverging populations is to detect the signatures of selective sweeps, which can be rather difficult in complex demographic scenarios, such as under secondary contact. Moreover, the detection of selective sweeps, especially in whole-genome data, often relies heavily on a narrow set of summary statistics that are affected by a multitude of factors, frequently leading to false positives and false negatives.

Correction to: The role of physical activity in metabolic homeostasis before and after the onset of type 2 diabetes: an IMI DIRECT study.

Unfortunately, 'Present address' was omitted from one of the addresses provided for Mark I. McCarthy (#26).

The role of physical activity in metabolic homeostasis before and after the onset of type 2 diabetes: an IMI DIRECT study.

Aims/hypothesis: It is well established that physical activity, abdominal ectopic fat and glycaemic regulation are related but the underlying structure of these relationships is unclear. The previously proposed twin-cycle hypothesis (TC) provides a mechanistic basis for impairment in glycaemic control through the interactions of substrate availability, substrate metabolism and abdominal ectopic fat accumulation. Here, we hypothesise that the effect of physical activity in glucose regulation is mediated by the twin-cycle.

Correction to: Physical activity intensity, bout-duration, and cardiometabolic risk markers in children and adolescents.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Doctors Rule: An Analysis of Health Ministers' Diaries in Australia.

Limited progress in nutrition policy action is often blamed on the close relationships the food industry has with health policy decision-makers. This analysis sought to examine this belief through the analysis of health ministers' diaries. Entries were downloaded from health ministers' diaries from two states in Australia from January 2013 to June 2018.

Discovery of biomarkers for glycaemic deterioration before and after the onset of type 2 diabetes: descriptive characteristics of the epidemiological studies within the IMI DIRECT Consortium.

Aims/hypothesis: Here, we describe the characteristics of the Innovative Medicines Initiative (IMI) Diabetes Research on Patient Stratification (DIRECT) epidemiological cohorts at baseline and follow-up examinations (18, 36 and 48 months of follow-up).

Methods: From a sampling frame of 24,682 adults of European ancestry enrolled in population-based cohorts across Europe, participants at varying risk of glycaemic deterioration were identified using a risk prediction algorithm (based on age, BMI, waist circumference, use of antihypertensive medication, smoking status and parental history of type 2 diabetes) and enrolled into a prospective cohort study (n = 2127) (cohort 1, prediabetes risk). We also recruited people from clinical registries with type 2 diabetes diagnosed 6-24 months previously (n = 789) into a second cohort study (cohort 2, diabetes).

Characteristics of hardware failure in patients undergoing surgical stabilization of rib fractures: A Chest Wall Injury Society multicenter study.

Background: Surgical stabilization of rib fractures (SSRF) is increasingly used for severe rib fractures/flail chest. There are no reports discussing mechanisms of failure of implanted hardware, its clinical presentation, or consequences. The purpose of this study was to evaluate the incidence, presenting signs, and clinical sequela of hardware failure after SSRF.

Specific physical activities, sedentary behaviours and sleep as long-term predictors of accelerometer-measured physical activity in 91,648 adults: a prospective cohort study.

Background: The evidence for the prospective relationships between specific physical activities (PA), sedentary behaviours (SB) and sleep on subsequent total PA levels is scarce. The purpose of this study was to examine prospective associations of self-reported PA, SB and sleep, and changes in these with subsequent accelerometer-measured PA.

Methods: A sub-sample of 91,648 UK Biobank participants reported moderate-to-vigorous PA (MVPA), lifestyle activities, TV viewing, computer use and sleep through screen-based questionnaires at baseline (2006-2010), and provided valid accelerometry data (dominant wrist-worn for 7 days between 2013 and 2015).

Driving status, travel modes and accelerometer-assessed physical activity in younger, middle-aged and older adults: a prospective study of 90 810 UK Biobank participants.

Background: Associations between driving and physical-activity (PA) intensities are unclear, particularly among older adults. We estimated prospective associations of travel modes with total PA, sedentary time (ST), light-intensity PA (LPA), and moderate-to-vigorous intensity PA (MVPA) among adults aged 39-70 years.

Methods: We studied 90 810 UK Biobank participants (56.

Estimating energy expenditure from wrist and thigh accelerometry in free-living adults: a doubly labelled water study.

Background: Many large studies have implemented wrist or thigh accelerometry to capture physical activity, but the accuracy of these measurements to infer activity energy expenditure (AEE) and consequently total energy expenditure (TEE) has not been demonstrated. The purpose of this study was to assess the validity of acceleration intensity at wrist and thigh sites as estimates of AEE and TEE under free-living conditions using a gold-standard criterion.

Methods: Measurements for 193 UK adults (105 men, 88 women, aged 40-66 years, BMI 20.

Descriptive epidemiology of changes in objectively measured sedentary behaviour and physical activity: six-year follow-up of the EPIC-Norfolk cohort.

Background: Sedentary time increases and total physical activity decreases with age. The magnitude and correlates of changes in sedentary time, light-intensity physical activity (LPA), moderate-to-vigorous intensity physical activity (MVPA), and overall physical activity remain unclear. We quantified these changes and identified their individual and sociodemographic correlates.

Using Accelerometers to Measure Physical Activity in Older Patients Admitted to Hospital.

Background: Low levels of physical activity in older patients during hospitalization have been linked to loss of functional ability. Practical methods of measuring physical activity are needed to better understand this association and to measure the efficacy of interventions. The aims of this study were to evaluate the feasibility of using accelerometers to discriminate between lying, sitting, standing, and standing and moving and to determine the acceptability of the method from the patients' perspective.