Deracemisation and stereoinversion by a nanoconfined bidirectional enzyme cascade: dual control by electrochemistry and selective metal ion activation.

The unique ability of the 'electrochemical leaf' (e-Leaf) to drive and control nanoconfined enzyme cascades bidirectionally, while directly monitoring their rate in real-time as electrical current, is exploited to achieve deracemisation and stereoinversion of secondary alcohols using a single electrode in one pot. Two alcohol dehydrogenase enzymes with opposing enantioselectivities, from (selective for ) and (selective for ) are driven bidirectionally coupling to the fast and quasi-reversible interconversion of NADP/NADPH catalysed by ferredoxin NADP reductase - all enzymes being co-entrapped in a nanoporous indium tin oxide electrode. Activity of the enzyme depends on the binding of a non-catalytic Mg, allowing it to be switched off after an oxidative half-cycle, by adding EDTA - the -selective enzyme, with a tightly-bound Zn, remaining fully active.

Repairing small type I hiatal hernias at the time of RYGB is not necessary to achieve resolution of reflux symptoms.

Introduction: Roux-en-Y gastric bypass (RYGB) is the gold standard operation for gastroesophageal reflux disease (GERD) in patients with severe obesity, but there is variability in surgeon opinion regarding whether small type I hiatal hernias (HH) require routine repair concurrently with RYGB. We sought to examine whether leaving small type I HHs unrepaired during RYGB affected GERD outcomes.

Methods: Pre-operatively our patients all receive endoscopy, and select patients with reflux symptoms receive esophagram based on attending surgeon practice and preference.

Antibiotic Prophylaxis for Megaprosthetic Reconstructions: Drug and Dosing May Matter More than Duration.

In orthopedic oncology, the implant of a megaprosthetic device is standard of care after large-scale tumor resection involving segmental removal of bone. Infection remains the leading cause of implant failure, often resulting in major morbidity. Perioperative antibiotic practices for megaprosthetic reconstructions are not standardized and are based on guidelines for conventional joint arthroplasties.

Chlorogenic Acid and Quercetin in a Diet with Fermentable Fiber Influence Multiple Processes Involved in DSS-Induced Ulcerative Colitis but Do Not Reduce Injury.

Ulcerative colitis (UC) patients often avoid foods containing fermentable fibers as some can promote symptoms during active disease. Pectin has been identified as a more protective fermentable fiber, but little has been done to determine the interaction between pectin and bioactive compounds present in foods containing that fiber type. Quercetin and chlorogenic acid, two bioactives in stone fruits, may have anti-cancer, anti-oxidant, and anti-inflammatory properties.

High p16 expression and heterozygous RB1 loss are biomarkers for CDK4/6 inhibitor resistance in ER breast cancer.

CDK4/6 inhibitors combined with endocrine therapy have demonstrated higher antitumor activity than endocrine therapy alone for the treatment of advanced estrogen receptor-positive breast cancer. Some of these tumors are de novo resistant to CDK4/6 inhibitors and others develop acquired resistance. Here, we show that p16 overexpression is associated with reduced antitumor activity of CDK4/6 inhibitors in patient-derived xenografts (n = 37) and estrogen receptor-positive breast cancer cell lines, as well as reduced response of early and advanced breast cancer patients to CDK4/6 inhibitors (n = 89).

Adapting, adopting, and advancing change: A framework for future research in the psychology of occupational safety.

Introduction: While there are numerous reviews of the research on the psychology of occupational safety, these studies provide weak guidance on where the research should go next. Accordingly, we introduce a simple framework for thinking about future research in this area: the adapting, adopting, and advancing change framework. This framework summarizes how external, technological, and theoretical developments have driven research in the psychology of occupational safety and uses these observations as evidence to imagine ways in which they may continue to do so.

Role of work breaks in well-being and performance: A systematic review and future research agenda.

Recovery from work is a critical component for employees' proper functioning. While research has documented the beneficial effects of after-work recovery, it has focused far less on the recovery that happens while in the form of work breaks. In this review, we systematically review available empirical evidence on the relationship between work breaks and well-being and performance among knowledge workers.

Neratinib in advanced HER2-positive breast cancer: experience from the royal Marsden hospital.

Purpose: To describe the tolerability and efficacy of neratinib as a monotherapy and in combination with capecitabine in advanced HER2-positive breast cancer in a real-world setting.

Methods: Patients who received neratinib for advanced HER2-positive at the Royal Marsden Hospital NHS Trust between August 2016 and May 2020 were identified from electronic patient records and baseline characteristics, previous treatment and response to treatment were recorded. The primary endpoint of the study was progression-free survival (PFS).

A Nanoconfined Four-Enzyme Cascade Simultaneously Driven by Electrical and Chemical Energy, with Built-in Rapid, Confocal Recycling of NADP(H) and ATP.

The importance of energized nanoconfinement for facilitating the study and execution of enzyme cascades that feature multiple exchangeable cofactors is demonstrated by experiments with carboxylic acid reductase (CAR), an enzyme that requires both NADPH and ATP during a single catalytic cycle. Conversion of cinnamic acid to cinnamaldehyde by a package of four enzymes loaded into and trapped in the random nanopores of an indium tin oxide (ITO) electrode is driven and monitored through the simultaneous delivery of electrical and chemical energy. The electrical energy is transduced by ferredoxin NADP reductase, which undergoes rapid, direct electron exchange with ITO and regenerates NADP(H).

Clinical Features and Treatment Outcomes of Pulmonary Complex With and Without Coinfections.

Coinfections are more common in patients with cystic fibrosis and bronchiectasis. Infiltrates on imaging studies are seen more commonly in patients with coinfections, but coinfections did not affect treatment outcomes of pulmonary complex.

Matrix Bound Nanovesicles Have Tissue-Specific Characteristics That Suggest a Regulatory Role.

Recent studies have identified an extracellular vesicle population that is tightly anchored within the extracellular matrix (ECM) of tissues and organs until released by matrix turnover events. Evidence suggests that these matrix-bound nanovesicles (MBVs) are a ubiquitous component of the ECM, raising questions regarding their tissue-specific identity and their biologic function(s). The primary objective of this study was to examine MBVs isolated from six different tissues and compare their physical and compositional characteristics to determine the common and differentially expressed features.

Use of a penicillin allergy clinical decision rule to enable direct oral penicillin provocation: an international multicentre randomised control trial in an adult population (PALACE): study protocol.

Introduction: Penicillin allergies are highly prevalent in the healthcare setting and associated with the prescription of second-line inferior antibiotics. More than 85% of all penicillin allergy labels can be removed by skin testing and 96%-99% of low-risk penicillin allergy labels can be removed by direct oral challenge. An internally and externally validated clinical assessment tool for penicillin allergy, PEN-FAST, can identify a low-risk penicillin allergy without the need for skin testing; a score of less than 3 has a negative predictive value of 96.

Impact of COVID-19 pandemic on pharmacist-led allergy assessments and penicillin skin testing.

Allergy assessments and penicillin skin testing are associated with reductions in high- infection (CDI)-risk antibiotic use and lower hospital-acquired CDI rates; however, these activities require substantial personnel and resource allocation. Recently, many antimicrobial stewardship programs' (ASPs) focus shifted towards supporting the COVID-19 pandemic response. We evaluated the impact of the COVID-19 pandemic on a pharmacist-led allergy assessment and penicillin skin testing program.

Measuring quality of dying, death and end-of-life care for children and young people: A scoping review of available tools.

Background: The circumstances and care provided at the end of a child's life have a profound impact on family members. Although assessing experiences and outcomes during this time is challenging, healthcare professionals have a responsibility to ensure high quality of care is provided.

Aim: To identify available tools which measure the quality of dying, death and end-of-life care for children and young people; describe the content, and data on validity and reliability of existing tools.

Advance Planning for Technology Use in Dementia Care: Development, Design, and Feasibility of a Novel Self-administered Decision-Making Tool.

Background: Monitoring technologies are used to collect a range of information, such as one's location out of the home or movement within the home, and transmit that information to caregivers to support aging in place. Their surveilling nature, however, poses ethical dilemmas and can be experienced as intrusive to people living with Alzheimer disease (AD) and AD-related dementias. These challenges are compounded when older adults are not engaged in decision-making about how they are monitored.

Developing good practice indicators to assist mental health practitioners to converse with young people about their online activities and impact on mental health: a two-panel mixed-methods Delphi study.

Background: Online activity has been linked to poor mental health in children and young people, particularly those with existing vulnerability who may inadvertently or otherwise access harmful content. It is suggested health and social care practitioners should address online activity during mental health consultations, but guidance about acceptable or effective ways to do this is lacking. This study sought to derive good practice guidance to support mental health practitioners to engage young people in conversations about their online activities and impact on mental health.

Glutamine addiction promotes glucose oxidation in triple-negative breast cancer.

Glutamine is a conditionally essential nutrient for many cancer cells, but it remains unclear how consuming glutamine in excess of growth requirements confers greater fitness to glutamine-addicted cancers. By contrasting two breast cancer subtypes with distinct glutamine dependencies, we show that glutamine-indispensable triple-negative breast cancer (TNBC) cells rely on a non-canonical glutamine-to-glutamate overflow, with glutamine carbon routed once through the TCA cycle. Importantly, this single-pass glutaminolysis increases TCA cycle fluxes and replenishes TCA cycle intermediates in TNBC cells, a process that achieves net oxidation of glucose but not glutamine.

Vinorelbine After Prior Treatment With Eribulin for Advanced Breast Cancer: A Single-Centre Experience Suggesting Cross-Resistance.

Introduction: The tubulin inhibitor, eribulin, improves survival for previously treated advanced breast cancer (ABC) compared to chemotherapy of physician's choice, including vinorelbine, an older anti-tubulin. Vinorelbine is commonly still used after eribulin, but potentially risks cross-resistance and its efficacy in this setting is unproven.

Materials And Methods: A retrospective analysis of all patients who received vinorelbine after prior eribulin (VAE) 2011-2015 and a parallel cohort of consecutive patients who received vinorelbine without prior eribulin (VWE) for previously treated ABC between 2005 and 2011.

ESMO recommendations on the use of circulating tumour DNA assays for patients with cancer: a report from the ESMO Precision Medicine Working Group.

Circulating tumour DNA (ctDNA) assays conducted on plasma are rapidly developing a strong evidence base for use in patients with cancer. The European Society for Medical Oncology convened an expert working group to review the analytical and clinical validity and utility of ctDNA assays. For patients with advanced cancer, validated and adequately sensitive ctDNA assays have utility in identifying actionable mutations to direct targeted therapy, and may be used in routine clinical practice, provided the limitations of the assays are taken into account.

Landscape of coronavirus disease 2019 clinical trials: New frontiers and challenges.

Background/aim: The number of coronavirus disease 2019 deaths and cases continues to increase globally. Novel therapies are urgently needed to treat patients with coronavirus disease 2019. We sought to provide a critical review of trials designed during the coronavirus disease 2019 pandemic.

Ancestral dietary change alters the development of larvae through MAPK signalling.

Studies in a broad range of animal species have revealed phenotypes that are caused by ancestral life experiences, including stress and diet. Ancestral dietary macronutrient composition and quantity (over- and under-nutrition) have been shown to alter descendent growth, metabolism and behaviour. Molecules have been identified in gametes that are changed by ancestral diet and are required for transgenerational effects.

Biomarkers for Systemic Therapy in Metastatic Breast Cancer: ASCO Guideline Update.

Purpose: To update the ASCO Biomarkers to Guide Systemic Therapy for Metastatic Breast Cancer (MBC) guideline.

Methods: An Expert Panel conducted a systematic review to identify randomized clinical trials and prospective-retrospective studies from January 2015 to January 2022.

Results: The search identified 19 studies informing the evidence base.