Developing Topics.

Background: Effective treatments are now available, which have demonstrated reductions in amyloid plaque burden while slowing cognitive decline in early symptomatic Alzheimer's disease (AD). Intervening before onset of cognitive impairment could provide greater benefit, particularly for individuals who carry an autosomal dominant mutation known to cause AD. To better guide the design of upcoming prevention trials, reliable sample size estimates for detecting relevant reductions in pathology are needed.

Effects of Route Complexity and Lighting on Route Following in Alzheimer's Disease and Posterior Cortical Atrophy.

Objective: Visual processing deficits arising in dementia are associated with particular functional disability. This study aimed to investigate the effects of the built environment on mobility and navigation in people with dementia-related visual loss.

Methods: Participants with posterior cortical atrophy (PCA; "visual-variant Alzheimer's"; n = 11), typical Alzheimer's disease (tAD; N = 10), and controls (n = 13) repeatedly walked down routes within a simplified real-world setting.

Sample size estimates for biomarker-based outcome measures in clinical trials in autosomal dominant Alzheimer's disease.

Introduction: Alzheimer disease (AD)-modifying therapies are approved for treatment of early-symptomatic AD. Autosomal dominant AD (ADAD) provides a unique opportunity to test therapies in presymptomatic individuals.

Methods: Using data from the Dominantly Inherited Alzheimer Network (DIAN), sample sizes for clinical trials were estimated for various cognitive, imaging, and CSF outcomes.

Transition Path Sampling Based Free Energy Calculations of Evolution's Effect on Rates in β-Lactamase: The Contributions of Rapid Protein Dynamics to Rate.

β-Lactamases are one of the primary enzymes responsible for antibiotic resistance and have existed for billions of years. The structural differences between a modern class A TEM-1 β-lactamase compared to a sequentially reconstructed Gram-negative bacteria β-lactamase are minor. Despite the similar structures and mechanisms, there are different functions between the two enzymes.

Effects of snake fungal disease (ophidiomycosis) on the skin microbiome across two major experimental scales.

Emerging infectious diseases are increasingly recognized as a significant threat to global biodiversity conservation. Elucidating the relationship between pathogens and the host microbiome could lead to novel approaches for mitigating disease impacts. Pathogens can alter the host microbiome by inducing dysbiosis, an ecological state characterized by a reduction in bacterial alpha diversity, an increase in pathobionts, or a shift in beta diversity.

The Evolution of the Acylation Mechanism in -Lactamase and Rapid Protein Dynamics.

-Lactamases are a class of well-studied enzymes that are known to have existed since billions of years ago, starting as a defense mechanism to stave off competitors and are now enzymes responsible for antibiotic resistance. Using ancestral sequence reconstruction, it is possible to study the crystal structure of a laboratory resurrected 2-3 billion year-old -lactamase. Comparing the ancestral enzyme to its modern counterpart, a TEM-1 -lactamase, the structural changes are minor, and it is probable that dynamic effects play an important role in the evolution of function.

Responses of diatoms and aquatic macroinvertebrates to deposited fine sediment in mesocosm channels as a basis for a new water quality guideline.

Water quality guidelines are an important tool for managing environmental pressures on freshwater streams. Currently, there is a lack of guideline values for fine sediment deposition in South Australian and, more broadly, Australian and overseas streams despite the potentially profound impacts of sediment deposition on aquatic communities. We used an outdoor recirculating stream mesocosm to assess the responses of freshwater diatoms and macroinvertebrates to fine sediment burial after six weeks following a pulsed event.

Biodiversity measures of a grassland plant-pollinator community are resilient to the introduction of honey bees (Apis mellifera).

The prairies of Canada support a diversity of insect pollinators that contribute pollination services to flowering crops and wild plants. Habitat loss and use of managed pollinators has increased conservation concerns for wild pollinators, as mounting evidence suggests that honey bees (Apis mellifera) may reduce their diversity and abundance. Plant-pollinator community analyses often omit non-bee pollinators, which can be valuable contributors to pollination services.

The Experience of Women Receiving Mastectomy Care in an Acute Surgical Ward: A Qualitative Study.

Aim: The research aim was to understand the inpatient experience of women who received postoperative care for mastectomy surgery in an acute surgical ward.

Design: A Qualitative Descriptive Research design was used.

Methods: The lead researcher conducted individual semi-structured interviews with 10 women who received postoperative care following mastectomy surgery in an acute hospital surgical ward.

High-Throughput Synthesis and Evaluation of Antiviral Copolymers for Enveloped Respiratory Viruses.

COVID-19 made apparent the devastating impact viral pandemics have had on global health and order. Development of broad-spectrum antivirals to provide early protection upon the inevitable emergence of new viral pandemics is critical. In this work, antiviral polymers are discovered using a combination of high-throughput polymer synthesis and antiviral screening, enabling diverse polymer compositions to be explored.

Key considerations for digital decentralised clinical trials from a feasibility study assessing pacing interventions for long COVID.

Post COVID-19 condition or long COVID is highly prevalent and often debilitating, with key symptoms including fatigue, breathlessness, and brain fog. There is currently a lack of evidence-based treatments for this highly complex syndrome. There is a need for clinical trial platforms to rapidly evaluate nonpharmacological treatments to support affected individuals with symptom management.

Evaluating the effectiveness of simvastatin in slowing the progression of disability in secondary progressive multiple sclerosis (MS-STAT2): protocol for a multicentre, randomised controlled, double-blind, phase 3 clinical trial in the UK.

Introduction: There remains a high unmet need for disease-modifying therapies that can impact disability progression in secondary progressive multiple sclerosis (SPMS). Following positive results of the phase 2 MS-STAT study, the MS-STAT2 phase 3 trial will evaluate the efficacy and cost-effectiveness of repurposed high-dose simvastatin in slowing the progression of disability in SPMS.

Methods And Analysis: MS-STAT2 will be a multicentre, randomised, placebo-controlled, double-blind trial of participants aged between 25 and 65 (inclusive) who have SPMS with an Expanded Disability Status Scale (EDSS) score of 4.

Evaluating the risk of data loss due to particle radiation damage in a DNA data storage system.

DNA data storage is a potential alternative to magnetic tape for archival storage purposes, promising substantial gains in information density. Critical to the success of DNA as a storage media is an understanding of the role of environmental factors on the longevity of the stored information. In this paper, we evaluate the effect of exposure to ionizing particle radiation, a cause of data loss in traditional magnetic media, on the longevity of data in DNA data storage pools.

Normothermic Regional Perfusion in Controlled Donation After Circulatory Death Liver Transplantation: A Systematic Review and Meta-Analysis.

Liver grafts from controlled donation after circulatory death (cDCD) donors have lower utilization rates due to inferior graft and patient survival rates, largely attributable to the increased incidence of ischemic cholangiopathy, when compared with grafts from brain dead donors (DBD). Normothermic regional perfusion (NRP) may improve the quality of cDCD livers to allow for expansion of the donor pool, helping to alleviate the shortage of transplantable grafts. A systematic review and metanalysis was conducted comparing NRP cDCD livers with both non-NRP cDCD livers and DBD livers.

The effects of Cannabis sativa and cannabinoids on the inhibition of pancreatic lipase - An enzyme involved in obesity.

Introduction: Obesity is a chronic noncommunicable disease characterized by excessive body fat that can have negative health consequences. Obesity is a complex disease caused by a combination of genetic, environmental, and lifestyle factors. It is characterized by a discrepancy between caloric intake and expenditure.

Pregnancy-Related Factors and Breast Cancer Risk for Women Across a Range of Familial Risk.

Importance: Few studies have investigated whether the associations between pregnancy-related factors and breast cancer (BC) risk differ by underlying BC susceptibility. Evidence regarding variation in BC risk is critical to understanding BC causes and for developing effective risk-based screening guidelines.

Objective: To examine the association between pregnancy-related factors and BC risk, including modification by a of BC where scores are based on age and BC family history.

Proactive integrated consultation-liaison psychiatry and time spent in hospital by older medical inpatients in England (The HOME Study): a multicentre, parallel-group, randomised controlled trial.

Background: Older people admitted to hospital in an emergency often have prolonged inpatient stays that worsen their outcomes, increase health-care costs, and reduce bed availability. Growing evidence suggests that the biopsychosocial complexity of their problems, which include cognitive impairment, depression, anxiety, multiple medical illnesses, and care needs resulting from functional dependency, prolongs hospital stays by making medical treatment less efficient and the planning of post-discharge care more difficult. We aimed to assess the effects of enhancing older inpatients' care with Proactive Integrated Consultation-Liaison Psychiatry (PICLP) in The HOME Study.

Genotypes and phenotypes in a -ant symbiosis.

The fitness effects of overt parasites, and host resistance to them, are well documented. Most symbionts, however, are more covert and their interactions with their hosts are less well understood. , an intracellular symbiont of insects, is particularly interesting because it is thought to be unaffected by the host immune response and to have fitness effects mostly focussed on sex ratio manipulation.

Exploring the preferences of traditional versus Western medicine in the Spiti Valley region of India: A qualitative approach.

Background: Traditional healing practices are prevalent in rural and mountainous areas of India where Western medicine is not accessible. WHO guidelines recommend integration of traditional and Western medicine to meet rural primary care needs. We explored three dimensions of rural patients' decision-making and satisfaction with their medical care: pregnancy-related concerns, pediatric care for children under five, and acute injuries.

Community health promotion and medical provision and impact on neonates (CHAMPION2) and support to rural India's public education system and impact on numeracy and literacy scores (STRIPES2): an update to the study protocol (v 11) for a cluster randomised trial in Madhya Pradesh, India.

Background: This update outlines amendments to the CHAMPION2/STRIPES2 cluster randomised trial protocol primarily made due to the COVID-19 pandemic and nationwide lockdown in India in 2020. These amendments were in line with national guidelines for health research during the COVID-19 pandemic.

Methods: We did not change the original trial design, eligibility, and outcomes.

Mitochondrial calcium overload contributes to cannabinoid-induced paraptosis in hormone-responsive breast cancer cells.

Studies have shown that natural products can induce paraptosis in tumour cell lines. Paraptosis is characterized by cytoplasmic vacuolation arising from the endoplasmic reticulum (ER) and mitochondria. The mechanism of paraptosis is unclear; however, dysregulation of Ca homeostasis is believed to affect paraptosis induction.

Statistical analysis plan for a cluster randomised trial in Madhya Pradesh, India: community health promotion and medical provision and impact on neonates (CHAMPION2).

Background: Neonatal mortality in India has fallen steadily and was estimated to be 24 per 1000 live births in the year 2017. However, neonatal mortality remains high in rural parts of the country. The Community Health Promotion and Medical Provision and Impact On Neonates (CHAMPION2) trial investigates the effect of a complex health intervention on neonatal mortality in the Satna District of Madhya Pradesh.