Raman active diyne-girder conformationally constrained p53 stapled peptides bind to MDM2 for visualisation without fluorophores.

Peptide stapling is an effective strategy to stabilise α-helical peptides, enhancing their bioactive conformation and improving physiochemical properties. In this study, we apply our novel diyne-girder stapling approach to the MDM2/MDMX α-helical binding region of the p53 transactivation domain. By incorporation of an unnatural amino acid to create an optimal , + 7 bridge length, we developed a highly α-helical stapled peptide, 4, confirmed circular dichroism.

The influence of emotional labor and emotional intelligence on cesarean section decision-making among midwives and obstetricians in Kosovo: A cross-sectional study using conjoint analysis.

Introduction: Cesarean section rates continue to increase worldwide. In 2021, one in every five deliveries was delivered by cesarean section. This is particularly alarming in resource-limited countries such as Kosovo, where the rates continue to increase and vary considerably between hospitals.

Non-mutated human tau stimulates Alzheimer's disease-relevant neurodegeneration in a microglia-dependent manner.

The accumulation of abnormal, non-mutated tau protein is a key pathological hallmark of Alzheimer's disease (AD). Despite its strong association with disease progression, the mechanisms by which tau drives neurodegeneration in the brain remain poorly understood. Here, we selectively expressed non-mutated or mutated human microtubule-associated protein tau () in neurons across the brain and observed neurodegeneration in the hippocampus, especially associated with non-mutated human tau.

Developmental axon diameter growth of central nervous system axons does not depend on ensheathment or myelination by oligodendrocytes.

Myelination facilitates the rapid conduction of action potentials along axons. In the central nervous system (CNS), myelinated axons vary over 100-fold in diameter, with conduction speed scaling linearly with increasing diameter. Axon diameter and myelination are closely interlinked, with axon diameter exerting a strong influence on myelination.

A randomised double-blind, placebo-controlled trial of pramipexole in addition to mood stabilisers for patients with treatment-resistant bipolar depression (the PAX-BD study).

Background: Options for 'treatment-resistant bipolar depression' (TRBD) are limited. Two small, short-term, trials of pramipexole suggest it might be an option.

Aims: To evaluate the clinical effectiveness and safety of pramipexole in the management of TRBD.

Fluoxetine and fractures after stroke: an individual patient data meta-analysis of three large randomised controlled trials of fluoxetine for stroke recovery.

Background: Observational studies have shown that selective serotonin reuptake inhibitors are associated with an increased risk of bone fractures, but the association can be confounded by indication and other sources of systematic bias that can be minimised in randomised controlled trials (RCTs).

Aim: Our aim was to report the rate, site, context, and predictors of fractures after stroke, and whether the fractures modified the effect of fluoxetine on modified Rankin score (mRS) at six months in an individual patient data meta-analysis of 5907 patients enrolled in three RCTs of fluoxetine (20mg for six months) for stroke recovery.

Methods: We classified fractures by treatment allocation, site (and thus likelihood of osteoporosis) and context, then performed multivariable analyses to explore independent predictors of fractures.

Association between epigenetic aging and atrioventricular block: a two-sample Mendelian randomization study.

Aims: Atrioventricular block (AVB) is a prevalent bradyarrhythmia. This study aims to investigate the causal effects of epigenetic aging, as inferred from DNA methylation profiles on the prevalence of AVB by Mendelian randomization (MR) analysis.

Methods: Genetic instruments for epigenetic aging and AVB were obtained from genome-wide association study data in the Edinburgh DataShare and FinnGen biobanks.

A qualitative exploration of change processes relevant to compassion-focused therapy that occurs when people view both soothing and non-soothing images.

Objective: Using soothing imagery within psychotherapy may support people to undertake positive visualisation exercises. However, little is known about what processes happen when people view images they find to be soothing or non-soothing.

Design: Exploratory qualitative methods were used.

Oronasal mucosal melanoma is defined by two transcriptional subtypes in humans and dogs with implications for diagnosis and therapy.

Mucosal melanoma is a rare melanoma subtype associated with a poor prognosis and limited existing therapeutic interventions, in part due to a lack of actionable targets and translational animal models for preclinical trials. Comprehensive data on this tumour type are scarce, and existing data often overlooks the importance of the anatomical site of origin. We evaluated human and canine oronasal mucosal melanoma (OMM) to determine whether the common canine disease could inform the rare human equivalent.

Patients' Attitudes Towards Integrating Environmental Sustainability Into Healthcare Decision-Making: An Interview Study.

Introduction: The ethical obligation to reduce the environmental impact of healthcare systems prompts an exploration of if and when environmental concerns should be integrated into clinical decision-making. In this study, we aimed to elucidate patients' attitudes regarding the provision of environmental information in healthcare decision-making and to identify preferred approaches for integrating these considerations into patient-provider consultations.

Methods: This interview study served as an in-depth follow-up of a survey study on gynaecological patients' perspectives on environmental sustainability within healthcare settings.

BMP6 participates in the molecular mechanisms involved in APAP hepatotoxicity.

Given the lack of accurate diagnostic methods of acetaminophen (APAP)-induced acute liver failure (ALF), the search for new biomarkers for its diagnosis is an urgent need. The aim of this study was to evaluate the role of bone morphogenetic protein 6 (BMP6) in APAP-induced ALF progression and its potential value as a biomarker of ALF. Hepatic and circulating BMP6 expression was assessed in APAP-treated mice and in serum samples from patients with APAP overdose.

Clinical diagnosis of cerebral amyloid angiopathy related hemorrhage in China: Simplified Edinburgh criteria and Boston criteria version 2.0.

Background: Accurate diagnosis of cerebral amyloid angiopathy (CAA) in surviving patients is indispensable for making treatment decisions and conducting clinical trials. We aimed to evaluate the diagnostic value and clinical utility of the simplified Edinburgh computed tomography (CT) criteria for CAA-related hemorrhage in Chinese patients.

Methods: We analyzed 212 patients with lobar hemorrhage who underwent brain CT and magnetic resonance imaging (MRI) from a multicentre cohort.

Novel adaptive immune systems in pristine Antarctic soils.

Antarctic environments are dominated by microorganisms, which are vulnerable to viral infection. Although several studies have investigated the phylogenetic repertoire of bacteria and viruses in these poly-extreme environments with freezing temperatures, high ultra violet irradiation levels, low moisture availability and hyper-oligotrophy, the evolutionary mechanisms governing microbial immunity remain poorly understood. Using genome-resolved metagenomics, we test the hypothesis that Antarctic poly-extreme high-latitude microbiomes harbour diverse adaptive immune systems.

Managing and mitigating future public health risks: Planetary boundaries, global catastrophic risk, and inclusive wealth.

There are two separate conceptualizations for assessing existential risks: Planetary Boundaries (PBs) and global catastrophic risks (GCRs). While these concepts are similar in principle, their underpinning literatures tend not to engage with each other. Research related to these concepts has tended to be siloed in terms of the study of specific threats and also in terms of how these are assumed to materialize; PBs attribute global catastrophes to slow-moving and potentially irreversible global changes, while GCRs focuses on cataclysmic short-term events.

Ethics and trustworthiness of artificial intelligence in Hepato-Pancreato-Biliary surgery: a snapshot of insights from the European-African Hepato-Pancreato-Biliary Association (E-AHPBA) survey.

Background: Hepato-Pancreato-Biliary (HPB) surgery is a complex specialty and Artificial Intelligence (AI) applications have the potential to improve pre- intra- and postoperative outcomes of HPB surgery. While ethics guidelines have been developed for the use of AI in clinical surgery, the ethical implications and reliability of AI in HPB surgery remain specifically unexplored.

Methods: An online survey was developed by the Innovation Committee of the E-AHPBA to investigate the current perspectives on the ethical principles and trustworthiness of AI in HPB Surgery among E-AHPBA membership.

Epidemiology of dog bite and strike related hospital admissions in Scotland, 1997 to 2022.

Objectives: To describe the epidemiology of dog-related injuries leading to hospital admission in Scotland and to estimate the direct health care costs.

Study Design: A retrospective, longitudinal analysis of Scottish hospital admissions coded under the W54 ICD-10 code 'bitten or struck by dog', 1997-2022.

Methods: Hospital admissions episodes coded under W54 were extracted from the SMR1/01 dataset.

Surgeon's imposter syndrome: a systematic review.

Introduction: Imposter syndrome (IS) refers to the psychological experience of imagining that one's achievements do not originate from one's own authentic competence. Surgeons are constantly faced with life-threatening decisions and can easily feel inadequate or insecure despite their years of training and experience. Imposter syndrome can distress surgeons at all career stages and has profound psychological and professional consequences.

The commercial roots of the genomic commons.

Accounts of the origins of the genomic commons typically focus on the development of public repositories and data-sharing agreements. This article tells a different story. During the 1990s in the United States, efforts of private companies to prevent the patenting of certain kinds of DNA sequences were essentially a conservative response to shifts in the sociotechnical constitution of the pharmaceutical innovation system, and to the operation of intellectual property as one of the key knowledge control regimes that regulate that system.

Does remission of type 2 diabetes matter? A qualitative study of healthcare professionals' perspectives and views about supporting remission in primary care.

Background: Trials conducted in highly selected populations have shown that type 2 diabetes (T2D) remission is possible, but the feasibility and acceptability of supporting remission in routine clinical practice remain uncertain.

Aim: We explored primary care professionals' perceptions and understandings of T2D remission and their views about supporting remission within routine clinical care.

Methods: Semi-structured interviews were conducted with 14 GPs and nine nurses working in Scottish general practices.

Management Measures and Trends of Biological Invasions in Europe: A Survey-Based Assessment of Local Managers.

Biological invasions are a major threat to biodiversity, ecosystem functioning and nature's contributions to people worldwide. However, the effectiveness of invasive alien species (IAS) management measures and the progress toward achieving biodiversity targets remain uncertain due to limited and nonuniform data availability. Management success is usually assessed at a local level and documented in technical reports, often written in languages other than English, which makes such data notoriously difficult to collect at large geographic scales.

A contentious intervention to support the medical workforce: a case study of the policy of introducing physician associates in the United Kingdom.

Background: Health systems across Europe are facing a workforce crisis, with some experiencing severe shortages of doctors. In response, many are exploring greater task-sharing, across established professions, such as doctors, nurses, and pharmacists, with patients and carers, and with new occupational groups, in particular ones that can assist doctors and relieve their workload.

Case Presentation: In the early 2000s the United Kingdom created a new occupational role, that of physician assistant.

The effect of Baby-Friendly Hospital Initiative compliance on the association between mode of birth and breastfeeding initiation in Sri Lanka.

Background: In Sri Lanka, there is some evidence that the likelihood of breastfeeding initiation varies by exposure to Baby-Friendly Hospital Initiative [BFHI]-compliant care and mode of birth. Globally, there is some evidence that exposure to mother-baby skin-to-skin contact (BFHI Step 4) is lower in caesarean section births. Therefore, we aimed to determine how breastfeeding initiation varies by mode of birth in Sri Lanka, and the extent to which women's exposure to BFHI practices explains any associations found.