Modeling the Potential Health, Health Economic, and Health Inequality Impact of a Large-Scale Rollout of the Drink Less App in England.

Objectives: Alcohol places a significant burden on the National Health Service (NHS); yet, uptake of cost-effective approaches remains low. Digital interventions may overcome some barriers to delivery. The Drink Less app has evidence of being effective at supporting heavier drinkers to reduce their alcohol intake.

Melleatin, an antibiofilm multitasking protein with rRNA N-glycosylase and nuclease activity from Armillaria mellea fruiting bodies.

Several studies highlight the identification of some enzymes with additional abilities, especially those involved in metabolic pathways and/or host defence processes, classified as multitasking proteins. In this context, we report the characterization of melleatin (17.5-kDa), a multitasking enzyme isolated from Armillaria mellea fruiting bodies.

Evaluating an early social communication intervention for young children with Down syndrome (ASCEND): results from a feasibility randomised control trial.

Background: This paper reports the results from a feasibility trial of an early parent-delivered social communication intervention for young children with Down syndrome ('ASCEND'). The intervention focuses on developing children's early social communication skills, in particular responding to shared attention. The aim was to inform the feasibility of running a full-scale trial through National Health Service (NHS) Speech and Language Therapy (SaLT) services, to assess whether the intervention is effective in improving language skills before children with Down syndrome start school.

Hyperthermic intraoperative peritoneal chemotherapy and cytoreductive surgery for people with peritoneal metastases: a systematic review and cost-effectiveness analysis.

Background: We compared the relative benefits, harms and cost-effectiveness of hyperthermic intraoperative peritoneal chemotherapy + cytoreductive surgery ± systemic chemotherapy versus cytoreductive surgery ± systemic chemotherapy or systemic chemotherapy alone in people with peritoneal metastases from colorectal, gastric or ovarian cancers by a systematic review, meta-analysis and model-based cost-utility analysis.

Methods: We searched MEDLINE, EMBASE, Cochrane Library and the Science Citation Index, ClinicalTrials.gov and WHO ICTRP trial registers until 14 April 2022.

A Randomised Controlled Trial of Early Vitrectomy and Intravitreal Antibiotics for Post-operative Exogenous Endophthalmitis (EVIAN study): study protocol for a feasibility trial.

Postoperative bacterial endophthalmitis is an infection of the eye's internal tissues resulting from an intraocular procedure. The condition is uncommon but can cause severe and irreversible impairment of sight. Standard management involves administration of antibiotics with or without subsequent removal of the infected vitreous gel by vitrectomy surgery.

Biochemical Characterisation of Sis: A Distinct Thermophilic PETase with Enhanced NanoPET Substrate Hydrolysis and Thermal Stability.

Polyethylene terephthalate (PET) degradation by enzymatic hydrolysis is significant for addressing plastic pollution and fostering sustainable waste management practices. Identifying thermophilic and thermostable PET hydrolases is particularly crucial for industrial bioprocesses, where elevated temperatures may enhance enzymatic efficiency and process kinetics. In this study, we present the discovery of a novel thermophilic and thermostable PETase enzyme named Sis, obtained through metagenomic sequence-based analysis.

Identifying the facilitators and barriers to implementation of renal tumour biopsy in the diagnostic pathway for small renal masses.

Objectives: To understand the facilitators and barriers to the implementation of renal tumour biopsy (RTB) in the diagnostic pathway for renal tumours in England.

Patients And Methods: Participants consisted of patients who had a renal tumour diagnosed and/or treated at one of five tertiary centres in England, healthcare professionals involved in the direct care of patients diagnosed with renal tumours, and clinical service managers and commissioners. The study employed a mixed-methods research methodology consisting of individual interviews and an on-line survey that explored the types of facilitators and barriers individuals perceived and experienced and the frequency in which these were reported.

Evaluating the Acceptability of the Drink Less App and the National Health Service Alcohol Advice Web Page: Qualitative Interview Process Evaluation.

Background: The extent to which interventions are perceived as acceptable to users impacts engagement and efficacy.

Objective: In this study, we evaluated the acceptability of (1) the smartphone app Drink Less (intervention) and (2) the National Health Service (NHS) alcohol advice web page (usual digital care and comparator) among adult drinkers in the United Kingdom participating in a randomized controlled trial evaluating the effectiveness of the Drink Less app.

Methods: A subsample of 26 increasing- and higher-risk drinkers (Alcohol Use Disorders Identification Test score≥8) assigned to the intervention group (Drink Less; n=14, 54%; female: n=10, 71%; age: 22-72 years; White: n=9, 64%) or usual digital care group (NHS alcohol advice web page; n=12, 46%; female: n=5, 42%; age: 23-68 years: White: n=9, 75%) took part in semistructured interviews.

Do engagement and behavioural mechanisms underpin the effectiveness of the Drink Less app?

This is a process evaluation of a large UK-based randomised controlled trial (RCT) (n = 5602) evaluating the effectiveness of recommending an alcohol reduction app, Drink Less, compared with usual digital care in reducing alcohol consumption in increasing and higher risk drinkers. The aim was to understand whether participants' engagement ('self-reported adherence') and behavioural characteristics were mechanisms of action underpinning the effectiveness of Drink Less. Self-reported adherence with both digital tools was over 70% (Drink Less: 78.

Cost-Effectiveness of the Baveno VI Criteria Compared With Endoscopy for High-Risk Varices in Patients With Child-Pugh A Cirrhosis.

Background & Aims: Although upper gastrointestinal endoscopy (EGD) remains the gold standard for detecting varices in cirrhosis, the Baveno VI criteria proposed a combination of transient elastography and platelet count that could rule out high-risk varices, therefore sparing the need for an endoscopy, with significant potential cost savings. We performed a cost-effectiveness analysis of the Baveno VI criteria compared with EGD in the diagnosis of high-risk varices in cirrhosis.

Methods: We built an analytical decision model to estimate the cost and benefits of using the Baveno VI criteria compared with EGD in patients with Child-Pugh A cirrhosis.

Effectiveness of a smartphone app (Drink Less) versus usual digital care for reducing alcohol consumption among increasing-and-higher-risk adult drinkers in the UK: a two-arm, parallel-group, double-blind, randomised controlled trial.

Background: Digital interventions, including apps and websites, can be effective for reducing alcohol consumption. However, many are not evidence- or theory-informed and have not been evaluated. We tested the effectiveness of the Drink Less app for reducing alcohol consumption compared with usual digital care in the UK.

Cytoreductive surgery plus hyperthermic intraoperative peritoneal chemotherapy for people with peritoneal metastases from colorectal, ovarian or gastric origin: A systematic review of randomized controlled trials.

Background: There is uncertainty in the relative benefits and harms of hyperthermic intraoperative peritoneal chemotherapy (HIPEC) when added to cytoreductive surgery (CRS) +/- systemic chemotherapy or systemic chemotherapy alone in people with peritoneal metastases from colorectal, gastric, or ovarian cancers.

Methods: We searched randomized controlled trials (RCTs) in the medical literature until April 14, 2022 and applied methods used for high-quality systematic reviews.

Findings: We included a total of eight RCTs (seven RCTs included in quantitative analysis as one RCT did not provide data in an analyzable format).

Phosphorylation of cardiac sodium channel at Ser571 anticipates manifestations of the aging myopathy.

Diastolic dysfunction and delayed ventricular repolarization are typically observed in the elderly, but whether these defects are intimately associated with the progressive manifestation of the aging myopathy remains to be determined. In this regard, aging in experimental animals is coupled with increased late Na current () in cardiomyocytes, raising the possibility that conditions the modality of electrical recovery and myocardial relaxation of the aged heart. For this purpose, aging male and female wild-type (WT) C57Bl/6 mice were studied together with genetically engineered mice with phosphomimetic (gain of function, GoF) or ablated (loss of function, LoF) mutations of the sodium channel Nav1.

A study protocol for a feasibility randomised controlled trial investigating videoendoscopic radical inguinal lymphadenectomy versus open radical inguinal lymphadenectomy in patients with penile cancer (VELRAD).

Background: Penile cancer is a rare male genital malignancy. Surgical excision of the primary tumour is followed by radical inguinal lymphadenectomy if there is metastatic disease detected by biopsy, fine needle aspiration cytology (FNAC) or following sentinel lymph node biopsy in patients with impalpable disease. However, radical inguinal lymphadenectomy is associated with a high morbidity rate, and there is increasing usage of a videoendoscopic approach as an alternative.

REMOTE-ILD study: Description of the protocol for a multicentre, 12-month randomised controlled trial to assess the clinical and cost-effectiveness of remote monitoring of spirometry and pulse oximetry in patients with interstitial lung disease.

Introduction: Remote monitoring of home physiological measurements has been proposed as a solution to support patients with chronic diseases as well as facilitating virtual consultations and pandemic preparedness for the future. Daily home spirometry and pulse oximetry have been demonstrated to be safe and acceptable to patients with interstitial lung disease (ILD) but there is currently limited evidence to support its integration into clinical practice.

Aim: Our aim is to understand the clinical utility of frequent remote physiological measurements in ILD and the impact of integrating these into clinical practice from a patient, clinical and health economic perspective.

Tailoring the stress response of human skin cells by substantially limiting the nuclear localization of angiogenin.

Human angiogenin (hANG) is the most studied stress-induced ribonuclease (RNase). In physiological conditions it performs its main functions in nucleoli, promoting cell proliferation by rDNA transcription, whereas it is strongly limited by its inhibitor (RNH1) throughout the rest of the cell. In stressed cells hANG dissociates from RNH1 and thickens in the cytoplasm where it manages the translational arrest and the recruitment of stress granules, thanks to its propensity to cleave tRNAs and to induce the release of active halves.

Cost-Effectiveness of Whole-Genome vs Whole-Exome Sequencing Among Children With Suspected Genetic Disorders.

Importance: The diagnosis of rare diseases and other genetic conditions can be daunting due to vague or poorly defined clinical features that are not recognized even by experienced clinicians. Next-generation sequencing technologies, such as whole-genome sequencing (WGS) and whole-exome sequencing (WES), have greatly enhanced the diagnosis of genetic diseases by expanding the ability to sequence a large part of the genome, rendering a cost-effectiveness comparison between them necessary.

Objective: To assess the cost-effectiveness of WGS compared with WES and conventional testing in children with suspected genetic disorders.

Metformin in the prevention of type 2 diabetes after gestational diabetes in postnatal women (OMAhA): a UK multicentre randomised, placebo-controlled, double-blind feasibility trial with nested qualitative study.

Objective: To determine the feasibility of a definitive trial of metformin to prevent type 2 diabetes in the postnatal period in women with gestational diabetes.

Design: A multicentre, placebo-controlled, double-blind randomised feasibility trial with qualitative evaluation.

Setting: Three inner-city UK National Health Service hospitals in London.

The Antimicrobial, Antibiofilm and Anti-Inflammatory Activities of P13#1, a Cathelicidin-like Achiral Peptoid.

Cationic antimicrobial peptides (CAMPs) are powerful molecules with antimicrobial, antibiofilm and endotoxin-scavenging activities. These properties make CAMPs very attractive drugs in the face of the rapid increase in multidrug-resistant (MDR) pathogens, but they are limited by their susceptibility to proteolytic degradation. An intriguing solution to this issue could be the development of functional mimics of CAMPs with structures that enable the evasion of proteases.

Nephron Sparing Treatment (NEST) for Small Renal Masses: A Feasibility Cohort-embedded Randomised Controlled Trial Comparing Percutaneous Cryoablation and Robot-assisted Partial Nephrectomy.

There is a paucity of high-level evidence on small renal mass (SRM) management, as previous classical randomised controlled trials (RCTs) failed to meet accrual targets. Our objective was to assess the feasibility of recruitment to a cohort-embedded RCT comparing cryoablation (CRA) to robotic partial nephrectomy (RPN). A total of 200 participants were recruited to the cohort, of whom 50 were enrolled in the RCT.

Simultaneous Irradiation with UV-A, -B, and -C Lights Promotes Effective Decontamination of Planktonic and Sessile Bacteria: A Pilot Study.

Surfaces in highly anthropized environments are frequently contaminated by both harmless and pathogenic bacteria. Accidental contact between these contaminated surfaces and people could contribute to uncontrolled or even dangerous microbial diffusion. Among all possible solutions useful to achieve effective disinfection, ultraviolet irradiations (UV) emerge as one of the most "Green" technologies since they can inactivate microorganisms via the formation of DNA/RNA dimers, avoiding the environmental pollution associated with the use of chemical sanitizers.

Exposure to Dichlorvos pesticide alters the morphology of and lipid metabolism in the ventral prostate of rats.

Organophosphate pesticides are widely used in agriculture, leading to soil, water, and food contamination. Among these compounds is Dichlorvos [O,O-dimethyl O-(2,2-dichlorovinyl)phosphate, DDVP], which is listed as a highly toxic compound by the Environmental Protection Agency and World Health Organization. Exposure to DDVP can result in nervous, respiratory, hepatic, and reproductive abnormalities, in addition to endocrine disrupting, mutagenic, and carcinogenic effects.

REFINE-Lung implements a novel multi-arm randomised trial design to address possible immunotherapy overtreatment.

Increasing evidence suggests that some immunotherapy dosing regimens for patients with advanced cancer could result in overtreatment. Given the high costs of these agents, and important implications for quality of life and toxicity, new approaches are needed to identify and reduce unnecessary treatment. Conventional two-arm non-inferiority designs are inefficient in this context because they require large numbers of patients to explore a single alternative to the standard of care.