How Do Gepotidacin and Zoliflodacin Stabilize DNA-Cleavage Complexes with Bacterial Type IIA Topoisomerases? 2. A Single Moving Metal Mechanism.

DNA gyrase is a bacterial type IIA topoisomerase that can create temporary double-stranded DNA breaks to regulate DNA topology and an archetypical target of antibiotics. The widely used quinolone class of drugs use a water-metal ion bridge in interacting with the GyrA subunit of DNA gyrase. Zoliflodacin sits in the same pocket as quinolones but interacts with the GyrB subunit and also stabilizes lethal double-stranded DNA breaks.

High Detection Rates for Prostate-specific Membrane Antigen-avid Prostate Cancer Recurrence at Low Prostate-specific Antigen levels on Extended Axial Field-of-view Positron Emission Tomography/Computed Tomography.

Background And Objective: Although prostate-specific membrane antigen (PSMA) positron emission tomography/computed tomography (PET/CT) has impacted the investigation and management of biochemical recurrence (BCR) of prostate cancer, negative scans are common at low rising prostate-specific antigen (PSA) levels. PET/CT devices with an extended axial field-of-view, such as the Siemens Biograph Vision Quadra (Quadra) scanner, have substantially higher sensitivity than conventional field-of-view scanners. Our aim was to assess whether the enhanced signal-to-noise ratios achieved on the Quadra scanner improve detection of low-volume disease and thereby increase detection of PC at low PSA levels.

Strategies for the design of biomimetic cell-penetrating peptides using AI-driven in silico tools for drug delivery.

Cell-penetrating peptides (CPP) have gained rapid attention over the last 25 years; this is attributed to their versatility, customisation, and 'Trojan horse' delivery that evades the immune system. However, the current CPP rational design process is limited, as it requires several rounds of peptide synthesis, prediction and wet-lab validation, which is expensive, time-consuming and requires extensive knowledge in peptide chemistry. Artificial intelligence (AI) has emerged as a promising alternative which can augment the design process, for example by determining physiochemical characteristics, secondary structure, solvent accessibility, disorder and flexibility, as well as predicting in vivo behaviour such as toxicity and peptidase degradation.

THE APPROACH TO A PREGNANCY AFTER BARIATRIC SURGERY.

With a rising worldwide incidence of obesity, particularly in the young, bariatric surgery offers an effective method of meaningful and sustained weight loss. At present, most bariatric procedures are carried out in women and increasingly in younger age groups. In line with the fertility benefits associated with weight loss, pregnancy after bariatric surgery is now a very common scenario.

ThF thin films for solid-state nuclear clocks.

After nearly 50 years of searching, the vacuum ultraviolet Th nuclear isomeric transition has recently been directly laser excited and measured with high spectroscopic precision. Nuclear clocks based on this transition are expected to be more robust than and may outperform current optical atomic clocks. These clocks also promise sensitive tests for new physics beyond the standard model.

Joint British Societies' position statement on cardiology training in the United Kingdom.

Cardiology training in the UK is facing significant challenges due to a range of factors. Recent curriculum changes have further compounded this issue and significantly risk the ability to produce adequately trained consultants capable of managing patients with increasingly complex cardiovascular disease. The introduction of mandatory dual accreditation in general internal medicine (GIM) alongside cardiology, by design, results in significantly reduced training opportunities, including procedural and subspecialty exposure.

Clinical phenotype of COVID-19 vaccine-associated myocarditis in Victoria, 2021-22: a cross-sectional study.

Objectives: To describe myocarditis as an adverse event after coronavirus disease 2019 (COVID-19) vaccination, including a detailed description of clinical phenotypes and diagnostic test results and differences by age, sex, and degree of troponin level elevation.

Study Design: Retrospective cross-sectional study.

Setting, Participants: Cases of suspected myocarditis following the administration of a COVID-19 vaccine in Victoria during 22 February 2021 - 30 September 2022 reported to Surveillance of Adverse Events Following Vaccination In the Community (SAEFVIC), with symptom onset within 14 days of vaccination, and deemed to be confirmed myocarditis according to the Brighton Collaboration Criteria.

Novel strategies to assess cytokine release mediated by chimeric antigen receptor T cells based on the adverse outcome pathway concept.

The success of cellular immunotherapies such as chimeric antigen receptor (CAR) T cell therapy has led to their implementation as a revolutionary treatment option for cancer patients. However, the safe translation of such novel immunotherapies, from non-clinical assessment to first-in-human studies is still hampered by the lack of suitable and models recapitulating the complexity of the human immune system. Additionally, using cells derived from human healthy volunteers in such test systems may not adequately reflect the altered state of the patient's immune system thus potentially underestimating the risk of life-threatening conditions, such as cytokine release syndrome (CRS) following CAR T cell therapy.

Improving medical students' responses to emergencies with a simulated cross-cover paging curriculum.

New residents are often unprepared to respond to medical emergencies. To address this gap, we implemented a simulated cross-cover paging curriculum. All senior medical students enrolled in a required specialty-specific (internal medicine, procedures, emergency medicine [EM], obstetrics and gynecology [OBGYN], family medicine and pediatrics) residency preparation course (RPC) in 2020-2021 participated.

Designing a regional clinical service for people with early-onset type 2 diabetes in England.

Aims: To design a regional clinical service for people with early-onset type 2 diabetes (EOT2D) in Leicester, Leicestershire and Rutland (England).

Methods: A literature search was undertaken to identify important considerations. A working group of key stakeholders was formed to design a triage system and service pathway.

Does work modify the relationship between violence and mental health among young people? Evidence from the Violence Against Children Surveys in Uganda, Nigeria and Colombia.

Background: Considering the well-established link between experiencing violence in childhood and poor mental health, it is important to understand the role of contextual factors in which young people live, learn, work, and play. Evidence has highlighted the importance of work as a contextual factor in the lives of young people, but it is unclear whether being in work mitigates, entrenches, or exacerbates the association between violence against children and poor mental health.

Methods: This study is based on nationally representative data of males and females aged 13-24 years who completed the Violence Against Children Surveys in Nigeria, Uganda, and Colombia.

British Cardiovascular Intervention Society Training Culture Focus Group Position Statement: Bringing Trainees and Trainers Together.

Unprofessional behaviour within cardiology has been well documented and commonly occurs within the cardiac catheterisation laboratory, with higher rates in interventional subspecialities. While most trainees have positive experiences and encounters within the catheterisation laboratory, around one in five report experiencing bullying. This not only has a significant negative impact on the individuals directly involved, but also on the wider multidisciplinary team; importantly, it will have a deleterious effect on patient safety.

How Do Gepotidacin and Zoliflodacin Stabilize DNA Cleavage Complexes with Bacterial Type IIA Topoisomerases? 1. Experimental Definition of Metal Binding Sites.

One of the challenges for experimental structural biology in the 21st century is to see chemical reactions happen. () DNA gyrase is a type IIA topoisomerase that can create temporary double-stranded DNA breaks to regulate DNA topology. Drugs, such as gepotidacin, zoliflodacin and the quinolone moxifloxacin, can stabilize these normally transient DNA strand breaks and kill bacteria.

Under pressure: Supporting academic faculty in demanding times.

Medical education has long relied upon the inherent rewards of teaching to secure necessary educators. In an era of increasing emphasis upon clinical productivity, the expectation of faculty engagement in medical education has been upended. In addition, the demands and stressors of modern medical education has contributed to the perceived cost of teaching by faculty.

Empowering Medical Students to Address Patient-Initiated Mistreatment at the Transition to Residency: An Education Quality Improvement Study.

Background: Mistreatment from patients is prevalent and has far-reaching negative consequences.

Aim: To develop a practice-based curriculum on patient-initiated mistreatment and examine participant perceptions before and after the curriculum.

Setting: Single medical school in the United States.

A combined electro-optical deformability micro-cytometer.

We have developed a deformability cytometer that simultaneously measures the optical and electrical shape change of single cells in a viscoelastic shear flow. The optical deformability of single cells is measured using a low-cost CMOS camera illuminated with a high-power LED triggered from an electrical impedance signal created by a passing cell. Simultaneously the electrical deformability of the cell is determined using electrode arrays that measure shape changes along different axes.

Opportunities to Improve Communication With Residency Applicants: Cross-Sectional Study of Obstetrics and Gynecology Residency Program Websites.

Background: As part of the residency application process in the United States, many medical specialties now offer applicants the opportunity to send program signals that indicate high interest to a limited number of residency programs. To determine which residency programs to apply to, and which programs to send signals to, applicants need accurate information to determine which programs align with their future training goals. Most applicants use a program's website to review program characteristics and criteria, so describing the current state of residency program websites can inform programs of best practices.

Burnout and Well-Being in Trainees: Findings From a National Survey of US Obstetrics and Gynecology Residents.

Despite national attention on resident well-being, challenges persist. Effective solutions require greater understanding of personal and program factors. To explore burnout, resilience, self-reported mental health, and perceptions of the learning environment in a national sample of obstetrics and gynecology (OB/GYN) residents.

Paternal undernutrition and overnutrition modify semen composition and preimplantation embryo developmental kinetics in mice.

Background: The importance of parental diet in relation to eventual offspring health is increasing in prominence due to the increased frequency of parents of reproductive age consuming poor diets. Whilst maternal health and offspring outcome have been studied in some detail, the paternal impacts are not as well understood. A father's poor nutritional status has been shown to have negative consequences on foetal growth and development and ultimately impact the long-term adult health of the offspring.

Establishing the Vaccine Safety Health Link: A large, linked data resource for the investigation of vaccine safety concerns.

Objective: Post-licensure vaccine safety surveillance of adverse events following immunisation is critical to ensure public safety and confidence in vaccines. This paper aims to describe the governance structure and data linkage methodology behind the establishment of the largest linked vaccine safety surveillance data resource in Australia - The Vaccine Safety Health Link (VSHL).

Methods: The Vaccine Safety Health Link contains linked records from the Australian Immunisation Register with records from hospital, perinatal, mortality, and notifiable disease datasets in near real-time.

The Work of Whiteness.

The division of the races, created for the economic and political purposes of justifying slavery and colonialism, is a deep, entrenched, social structure which creates and promotes white privilege and is one within which we all live. No one can be free from it. This presentation is rooted in the assumption that the problem of racism today is a problem of whiteness and that it is an examination of this construct, therefore, which needs to be central to seeking a solution to this destructive dynamic.