Development of small molecule non-covalent coronavirus 3CL protease inhibitors from DNA-encoded chemical library screening.

Variants of SARS-CoV-2 have continued to emerge across the world and cause hundreds of deaths each week. Due to the limited efficacy of vaccines against SARS-CoV-2 and resistance to current therapies, additional anti-viral therapeutics with pan-coronavirus activity are of high interest. Here, we screen 2.

Polypharmacy in primary care: A population-based retrospective cohort study of electronic health records.

Background: Polypharmacy, prescription of multiple medications to a patient, is a major challenge for health systems. There have been no peer-reviewed studies of polypharmacy prevalence and medication cost at a population level in England.

Aims: To determine prevalence and medication cost of polypharmacy, by patient characteristics.

Characteristics associated with influenza vaccination uptake in pregnancy: a retrospective cohort study.

Background: Pregnant women are at increased risk from influenza, yet maternal influenza vaccination levels remain suboptimal.

Aim: To estimate associations between sociodemographic and health characteristics and seasonal influenza vaccination uptake among pregnant women, and to understand trends over time to inform interventions to improve vaccine coverage.

Design And Setting: Retrospective cohort study using linked electronic health records of women in North West London with a pregnancy overlapping an influenza season between September 2010 and February 2020.

Factors associated with accessing long-term adult social care in people aged 75 and over: a retrospective cohort study.

Background: An ageing population and limited resources have put strain on state provision of adult social care (ASC) in England. With social care needs predicted to double over the next 20 years, there is a need for new approaches to inform service planning and development, including through predictive models of demand.

Objective: Describe risk factors for long-term ASC in two inner London boroughs and develop a risk prediction model for long-term ASC.

Nonsurgical Periodontal Therapy in CKD: Findings of the Kidney and Periodontal Disease (KAPD) Pilot Randomized Controlled Trial.

Rationale & Objective: Observational studies have suggested that periodontal disease may be a modifiable risk factor for chronic kidney disease (CKD). The Kidney and Periodontal Disease (KAPD) Study was designed to determine the feasibility of conducting a periodontal disease treatment trial among a high-risk (mostly poor and racial/ethnic minority) population and estimate the magnitude and variability of kidney and inflammatory biomarker levels in response to intensive periodontal treatment.

Study Design: Single-center, unmasked, intention-to-treat, randomized, controlled, pilot trial with 2:1 allocation to the treatment and comparison groups.

Myocardial injection of a thermoresponsive hydrogel with reactive oxygen species scavenger properties improves border zone contractility.

The decrease in contractility in myocardium adjacent (border zone; BZ) to a myocardial infarction (MI) is correlated with an increase in reactive oxygen species (ROS). We hypothesized that injection of a thermoresponsive hydrogel, with ROS scavenging properties, into the MI would decrease ROS and improve BZ function. Fourteen sheep underwent antero-apical MI.

The role of patients and carers in diffusing a health-care innovation: A case study of "My Medication Passport".

Background: Patients are increasingly recognized as playing important roles in improving health services. Little is known about the mechanisms by which patients develop and diffuse local innovations in a complex health-care system.

Objective: To ascertain how diffusion of an innovation, My Medication Passport, occurred and roles played by patients in it.

Reversal of right ventricular failure by chronic α-subtype adrenergic agonist therapy.

Right ventricular (RV) failure (RVF) is a serious disease with no effective treatment available. We recently reported a disease prevention study showing that chronic stimulation of α-adrenergic receptors (α-ARs), started at the time of RV injury, prevented the development of RVF. The present study used a clinically relevant disease reversal design to test if chronic α-AR stimulation, started after RVF was established, could reverse RVF.

Influence of Incident Wavelength and Detector Material Selection on Fluorescence in the Application of Raman Spectroscopy to a Fungal Fermentation Process.

Raman spectroscopy is a novel tool used in the on-line monitoring and control of bioprocesses, offering both quantitative and qualitative determination of key process variables through spectroscopic analysis. However, the wide-spread application of Raman spectroscopy analysers to industrial fermentation processes has been hindered by problems related to the high background fluorescence signal associated with the analysis of biological samples. To address this issue, we investigated the influence of fluorescence on the spectra collected from two Raman spectroscopic devices with different wavelengths and detectors in the analysis of the critical process parameters (CPPs) and critical quality attributes (CQAs) of a fungal fermentation process.

The expression of two isoforms of matrix metalloproteinase-2 in aged mouse models of diabetes mellitus and chronic kidney disease.

Background: This study was undertaken to explore the effects of aging on the kidneys in mouse models of diabetes and chronic kidney disease (CKD), and to compare the expression of two isoforms of matrix metalloproteinase-2 (MMP-2)-secretory full-length MMP-2 and intracellular N-terminal truncated MMP-2 (NTT-MMP-2)-in these models.

Methods: Two experimental ICR mouse models were used: a streptozotocin (STZ)-induced type 1 diabetes mellitus model and a 5/6 nephrectomized (5/6Nx) CKD model. The abundance of each isoform of MMP-2 was determined by quantitative polymerase chain reaction (qPCR), and functional analyses were conducted.

The two isoforms of matrix metalloproteinase- 2 have distinct renal spatial and temporal distributions in murine models of types 1 and 2 diabetes mellitus.

Background: We recently reported on the enhanced tubular expression of two discrete isoforms of the MMP-2 (full length and N-terminal truncated, FL-MMP-2, NTT-MMP-2) in a murine model and human diabetic kidneys. In the present study, we examined in more detail the temporal and spatial distributions of MMP-2 isoform expression in murine models of Type 1 and Type 2 diabetes mellitus.

Methods: Diabetic models were streptozotocin (STZ)-induced diabetes (Type 1 diabetes mellitus) and db/db mice (Type 2 diabetes mellitus).

Short term doxycycline treatment induces sustained improvement in myocardial infarction border zone contractility.

Decreased contractility in the non-ischemic border zone surrounding a MI is in part due to degradation of cardiomyocyte sarcomeric components by intracellular matrix metalloproteinase-2 (MMP-2). We recently reported that MMP-2 levels were increased in the border zone after a MI and that treatment with doxycycline for two weeks after MI was associated with normalization of MMP-2 levels and improvement in ex-vivo contractile protein developed force in the myocardial border zone. The purpose of the current study was to determine if there is a sustained effect of short term treatment with doxycycline (Dox) on border zone function in a large animal model of antero-apical myocardial infarction (MI).

Non-Alcoholic Beverage Cues as Specific Comparison Images to Alcohol Image Cues.

Background: Visual alcohol cues are often used to elicit craving (e.g., cue-reactivity), and selection of appropriate comparison cues is important to isolate the specific effect of craving for alcohol.

α-Subtype adrenergic agonist therapy for the failing right ventricle.

Failure of the right ventricle (RV) is a serious disease with a poor prognosis and limited treatment options. Signaling by α-adrenergic receptors (α-ARs), in particular the α-subtype, mediate cardioprotective effects in multiple heart failure models. Recent studies have shown that chronic treatment with the α-subtype agonist A61603 improves function and survival in a model of left ventricular failure.

Are nurses meeting the needs of men in primary care?

Meeting men's health needs by improving healthcare service access is a key objective of comprehensive primary health care. The aims of this qualitative study were to explore the perception of nurses in men's health services and to describe men's expectation of the nurse. The comparative component identifies the barriers and facilitators to improved access to health services.

Hyperpolarized C magnetic resonance evaluation of renal ischemia reperfusion injury in a murine model.

Acute kidney injury (AKI) is a major risk factor for the development of chronic kidney disease (CKD). Persistent oxidative stress and mitochondrial dysfunction are implicated across diverse forms of AKI and in the transition to CKD. In this study, we applied hyperpolarized (HP) C dehydroascorbate (DHA) and C pyruvate magnetic resonance spectroscopy (MRS) to investigate the renal redox capacity and mitochondrial pyruvate dehydrogenase (PDH) activity, respectively, in a murine model of AKI at baseline and 7 days after unilateral ischemia reperfusion injury (IRI).

Clear Cell Renal Cell Carcinoma is linked to Epithelial-to-Mesenchymal Transition and to Fibrosis.

Clear cell renal cell carcinoma (ccRCC) represents the most common type of kidney cancer with high mortality in its advanced stages. Our study aim was to explore the correlation between tumor epithelial-to-mesenchymal transition (EMT) and patient survival. Renal biopsies of tumorous and adjacent nontumorous tissue were taken with a 16 g needle from our patients ( = 26) undergoing partial or radical nephrectomy due to ccRCC RNA sequencing libraries were generated using Illumina TruSeq Access library preparation protocol and TruSeq Small RNA library preparation kit.

An intracellular matrix metalloproteinase-2 isoform induces tubular regulated necrosis: implications for acute kidney injury.

Acute kidney injury (AKI) causes severe morbidity, mortality, and chronic kidney disease (CKD). Mortality is particularly marked in the elderly and with preexisting CKD. Oxidative stress is a common theme in models of AKI induced by ischemia-reperfusion (I-R) injury.

Enhanced expression of two discrete isoforms of matrix metalloproteinase-2 in experimental and human diabetic nephropathy.

Background: We recently reported on the enhanced expression of two isoforms of matrix metalloproteinase-2 (MMP-2) in human renal transplantation delayed graft function. These consist of the conventional secreted, full length MMP-2 isoform (FL-MMP-2) and a novel intracellular N-Terminal Truncated isoform (NTT-MMP-2) generated by oxidative stress-mediated activation of an alternate promoter in the MMP-2 first intron. Here we evaluated the effect of hyperglycemia and diabetes mellitus on the in vitro and in vivo expression of the two MMP-2 isoforms.

The Kidney and Periodontal Disease (KAPD) study: A pilot randomized controlled trial testing the effect of non-surgical periodontal therapy on chronic kidney disease.

Introduction: Chronic kidney disease (CKD) remains a prevalent public health problem that disproportionately affects minorities and the poor, despite intense efforts targeting traditional risk factors. Periodontal diseases are common bacterial plaque-induced inflammatory conditions that can respond to treatment and have been implicated as a CKD risk factor. However there is limited evidence that treatment of periodontal disease slows the progression of CKD.

A spreadsheet calculator for estimating biogas production and economic measures for UK-based farm-fed anaerobic digesters.

This paper presents a spreadsheet calculator to estimate biogas production and the operational revenue and costs for UK-based farm-fed anaerobic digesters. There exist sophisticated biogas production models in published literature, but the application of these in farm-fed anaerobic digesters is often impractical. This is due to the limited measuring devices, financial constraints, and the operators being non-experts in anaerobic digestion.

Quantifying the prevalence of frailty in English hospitals.

Objectives: Population ageing has been associated with an increase in comorbid chronic disease, functional dependence, disability and associated higher health care costs. Frailty Syndromes have been proposed as a way to define this group within older persons. We explore whether frailty syndromes are a reliable methodology to quantify clinically significant frailty within hospital settings, and measure trends and geospatial variation using English secondary care data set Hospital Episode Statistics (HES).