Roadmap to advance therapeutics for -related disorder: a patient organization perspective from SynGAP Research Fund.

-related disorder (SRD) is a developmental and epileptic encephalopathy caused by a disruption of the gene. At the beginning of 2024, it is one of many rare monogenic brain disorders without disease-modifying treatments, but that is changing. This article chronicles the last 5 years, beginning when treatments for SRD were not publicly in development, to the start of 2024 when many SRD-specific treatments are advancing.

Outcomes, mortality risk factors, and functional status post-Norwood: A single-center study.

Background: The Norwood operation (NO) for infants with univentricular physiology has high interstage mortality. This study evaluated outcomes and risk factors for mortality following NO.

Methods: Retrospective single-center study of patients undergoing NO from 2010 to 2020.

Determining the association of hyperoxia while on extracorporeal life support with mortality in neonates following Norwood operation.

Background: Patients requiring extracorporeal life support (ECLS) support post-Norwood operation constitute an extremely high-risk group.

Materials And Methods: We retrospectively aimed to evaluate the relationship of hyperoxia with mortality and other clinical outcomes in patients who required ECLS following Norwood operation between January/2010 and December/2020 in a large volume center.

Results: During the study period 65 patients required ECLS post-Norwood.

Impact of solar geoengineering on temperature-attributable mortality.

Decisions about solar geoengineering (SG) entail risk-risk tradeoffs between the direct risks of SG and SG's ability to reduce climate risks. Quantitative comparisons between these risks are needed to inform public policy. We evaluate idealized SG's effectiveness in reducing deaths from warming using two climate models and an econometric analysis of temperature-attributable mortality.

What Characteristics Modify the Relation of Neighborhood Walkability and Walking Behavior in Older Adults?

Background And Objectives: Neighborhood walkability can influence walking behaviors in older adults. However, its associations of walkability with walking may differ by demographic, socioeconomic, health, social, and residential characteristics due to factors such as increased vulnerability to environmental factors or increased resilience.

Research Design And Methods: In a sample of older adults ( = 493, median age = 82 [range 78-89], 56% female, 31% Black), a walkability index was derived from audits of Google Street View images of participants' immediate neighborhoods.

An advanced in silico model of the oral mucosa reveals the impact of extracellular spaces on chemical permeation.

Accurately predicting the permeation of chemicals through human epithelial tissues is crucial for pharmaceutical therapeutic design and toxicology. Current mathematical models of multi-layered stratified squamous epithelium such as those in the oral cavity use simplistic 'bricks and mortar' geometries that do not fully account for the complex cellular architecture that may affect chemical permeation in these tissues. Here we aimed to develop a new, advanced mechanistic mathematical model of the human epithelium that more accurately represents chemical tissue permeation.

Abortive infection of bat fibroblasts with SARS-CoV-2.

Bats are tolerant to highly pathogenic viruses such as Marburg, Ebola, and Nipah, suggesting the presence of a unique immune tolerance toward viral infection. Here, we compared severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection of human and bat () pluripotent cells and fibroblasts. Since bat cells do not express an angiotensin-converting enzyme 2 (ACE2) receptor that allows virus infection, we transduced the human ACE2 (hA) receptor into the cells and found that transduced cells can be infected with SARS-CoV-2.

Comparing the different phenotypes of diabetes in pregnancy: Are outcomes worse for women with young-onset type 2 diabetes compared to type 1 diabetes?

Aims: Pregnancies are increasingly affected by young-onset type 2 diabetes mellitus (YT2DM), an aggressive phenotype associated with a higher vascular risk profile compared to type 1 diabetes mellitus (T1DM). We compared pregnancy outcomes to illuminate areas where differing management guidance might be needed.

Methods: This retrospective single-centre study (2010 2019) included 259 singleton pregnancies affected by pregestational T1DM (N = 124) or YT2DM (N = 135) diagnosed at < 40 years.

Collaboration, coordination and communication as facilitators of transitions for patients with advanced cancer: a scoping review linked to the Pal-Cycles project.

Background: Person-centred care is becoming increasingly recognised as an important element of palliative care. The current review syntheses evidence in relation to transitions in advanced cancer patients with palliative care needs. The review focuses on specific elements which will inform the Pal-Cycles programme, for patients with advanced cancer transitioning from hospital care to community care.

Feeder-free culture of human pluripotent stem cells drives MDM4-mediated gain of chromosome 1q.

Culture-acquired variants in human pluripotent stem cells (hPSCs) hinder their applications in research and clinic. However, the mechanisms that underpin selection of variants remain unclear. Here, through analysis of comprehensive karyotyping datasets from over 23,000 hPSC cultures of more than 1,500 lines, we explored how culture conditions shape variant selection.

Alpha2 Agonist Use in Critically Ill Adults: A Focus on Sedation and Withdrawal Prevention.

The management of sedation in critically ill adults poses a unique challenge to clinicians. Dexmedetomidine, an α agonist, has a unique mechanism and favorable pharmacokinetics, making it an attractive intravenous option for sedation and delirium in the intensive care unit. However, patients may be at risk for withdrawal with prolonged use, adding to the complexity of sedation and agitation management in this patient population.

Ambient air pollution and the risk of violence in primary and secondary school settings: a cross-sectional study.

Background: Individual and social characteristics are attributed to violent behavior in schools, yet environmental hazards may play an understudied role. Ambient air pollution has been linked to neurological dysfunction that inhibits decision-making and may result in violent behavior in adult populations. However, little is known on how air pollution may be associated with violent behaviors in children.

The future of hospital at home: a qualitative interview study of healthcare staff.

Purpose: Hospital at Home (HaH) services are expanding to provide acute multidisciplinary care in an individual's home. In this pilot study, we interviewed HaH staff to understand challenges and opportunities for service development.

Methods: We conducted 23 semi-structured interviews with multidisciplinary staff working across three HaH services in Scotland.

Understanding the Impacts of Online Mental Health Peer Support Forums: Realist Synthesis.

Background: Online forums are widely used for mental health peer support. However, evidence of their safety and effectiveness is mixed. Further research focused on articulating the contexts in which positive and negative impacts emerge from forum use is required to inform innovations in implementation.

Patients Aged 80 or More With Distal Radius Fractures Have a Lower One-Year Mortality Rate Than Age- and Gender-Matched Controls: A Register-Based Study.

Introduction: With a rapidly ageing population, the number of distal radius fractures (DRFs) in the elderly will increase dramatically. The aim of this retrospective register study was to examine the 1- and 5-year mortality in DRF patients aged 80 years or more and correlate the overall survival to factors not related to the fracture itself.

Material And Methods: Patients aged ≥80 diagnosed with DRFs in Lund University Hospital in Sweden in the period 2010-2012 were extracted from the prospective Lund Distal Radius Fracture register.

Long term care facilities in England during the COVID-19 pandemic-a scoping review of guidelines, policy and recommendations.

Background: The disproportionate effect of COVID-19 on long term care facility (LTCF) residents has highlighted the need for clear, consistent guidance on the management of pandemics in such settings. As research exploring the experiences of LTCFs during the pandemic and the implications of mass hospital discharge, restricting staff movement, and limiting visitation from relatives are emerging, an in-depth review of policies, guidance and recommendations issued during this time could facilitate wider understanding in this area.

Aims: To identify policies, guidance, and recommendations related to LTCF staff and residents, in England issued by the government during the COVID-19 pandemic, developing a timeline of key events and synthesizing the policy aims, recommendations, implementation and intended outcomes.

Short-Term Outcomes, Functional Status, and Risk Factors for Requiring Extracorporeal Life Support After Norwood Operation: A Single-Center Retrospective Study.

Patients requiring extracorporeal life support (ECLS) post-Norwood operation constitute an extremely high-risk group. We retrospectively described short-term outcomes, functional status, and assessed risk factors for requiring ECLS post-Norwood operation between January 2010 and December 2020 in a high-volume center. During the study period, 269 patients underwent a Norwood procedure of which 65 (24%) required ECLS.

Human otic progenitor cell models of congenital hearing loss reveal potential pathophysiologic mechanisms of Zika virus and cytomegalovirus infections.

Unlabelled: Congenital hearing loss is a common chronic condition affecting children in both developed and developing nations. Viruses correlated with congenital hearing loss include human cytomegalovirus (HCMV) and Zika virus (ZIKV), which causes congenital Zika syndrome. The mechanisms by which HCMV and ZIKV infections cause hearing loss are poorly understood.

Do people with dementia and carers get what they need? Barriers in social care and carers needs assessments.

Background: People with dementia and unpaid carers need to go through a social care or carers needs assessment to access and receive subsidised or fully-funded social care. With no previous evidence, this qualitative study aimed to provide insights into the access to, experiences of receiving and conducting social care or carers needs assessments, and access to social care.

Methods: Unpaid carers of people with dementia and professionals conducting social care or carers needs assessment living or working in England were interviewed remotely about their experiences between April and August 2023.

Rapid spin changes around a magnetar fast radio burst.

Magnetars are neutron stars with extremely high magnetic fields (≳10 gauss) that exhibit various X-ray phenomena such as sporadic subsecond bursts, long-term persistent flux enhancements and variable rotation-period derivative. In 2020, a fast radio burst (FRB), akin to cosmological millisecond-duration radio bursts, was detected from the Galactic magnetar SGR 1935+2154 (refs. ), confirming the long-suspected association between some FRBs and magnetars.