POLR3B is associated with a developmental and epileptic encephalopathy with myoclonic-atonic seizures and ataxia.

Objective: POLR3B encodes the second largest subunit of RNA polymerase III, which is essential for transcription of small non-coding RNAs. Biallelic pathogenic variants in POLR3B are associated with an inherited hypomyelinating leukodystrophy. Recently, de novo heterozygous variants in POLR3B were reported in six individuals with ataxia, spasticity, and demyelinating peripheral neuropathy.

Dying with and of dementia.

Aim: With an ageing population the prevalence of dementia increases. A healthcare crisis is looming.

Method: Dementia is a terminal condition.

Predictors of Pain and Mood Disturbances Among Older People in Custody Using an interRAI Assessment.

The population of people in federal custody in Canada is aging. Those in custody report experiencing poorer health and high rates of chronic health conditions. Two health concerns that are disproportionately higher among those in custody are mood disorders and pain.

No-fault compensation schemes for COVID-19 vaccine injury: a mixed bag for claimants and citizens.

The development of vaccines against SARS-CoV-2 (COVID-19) presented a unique set of challenges. There was a global need for safe, effective vaccines against a new virus. In response to the development of vaccines for COVID-19 (some of which used novel technologies), there was a proliferation of no-fault compensation schemes (NFCS) for COVID-19 vaccine injuries.

Transcriptional control of a metabolic switch regulating cellular methylation reactions is part of a common response to stress in divergent bee species.

Recent global declines in bee health have elevated the need for a more complete understanding of the cellular stress mechanisms employed by diverse bee species. We recently uncovered the biomarker lethal (2) essential for life [l(2)efl] genes as part of a shared transcriptional program in response to a number of cell stressors in the western honey bee (Apis mellifera). Here, we describe another shared stress-responsive gene, glycine N-methyltransferase (Gnmt), which is known as a key metabolic switch controlling cellular methylation reactions.

FANCJ promotes PARP1 activity during DNA replication that is essential in BRCA1 deficient cells.

The effectiveness of poly (ADP-ribose) polymerase inhibitors (PARPi) in creating single-stranded DNA gaps and inducing sensitivity requires the FANCJ DNA helicase. Yet, how FANCJ relates to PARP1 inhibition or trapping, which contribute to PARPi toxicity, remains unclear. Here, we find PARPi effectiveness hinges on S-phase PARP1 activity, which is reduced in FANCJ deficient cells as G-quadruplexes sequester PARP1 and MSH2.

FANCJ promotes PARP1 activity during DNA replication that is essential in BRCA1 deficient cells.

Single-stranded DNA gaps are postulated to be fundamental to the mechanism of anti-cancer drugs. Gaining insights into their induction could therefore be pivotal for advancing therapeutic strategies. For poly (ADP-ribose) polymerase inhibitors (PARPi) to be effective, the presence of FANCJ helicase is required.

Children in street situations' access to healthcare: qualitative findings from the Street Child World Cup 2022.

Background: Children in street situations (those who live or work on the street) are known to face barriers in accessing healthcare.

Methods: The study combined a remote survey with 33 adult non-governmental organisation (NGO) staff members, in-depth interviews with staff members of 11 NGOs and 4 formerly street-connected adult young leaders and a questionnaire with 30 street-connected children from 15 countries participating in the Street Child World Cup event in Qatar in 2022. Data were analysed using thematic analysis.

Longitudinal impact of COVID-19 pandemic on the utilization of hemoglobin A1c testing in outpatients.

Background: During the COVID-19 pandemic, concerns arose about disparate access to health care and laboratory testing. There is limited information about the pandemic's impact on the frequency of diabetic laboratory testing across demographic subgroups (e.g.

Propionic acid induces alterations in mitochondrial morphology and dynamics in SH-SY5Y cells.

Propionic acid (PPA) is used to study the role of mitochondrial dysfunction in neurodevelopmental conditions like autism spectrum disorders. PPA is known to disrupt mitochondrial biogenesis, metabolism, and turnover. However, the effect of PPA on mitochondrial dynamics, fission, and fusion remains challenging to study due to the complex temporal nature of these mechanisms.

Development of a patient and clinician co-led education program to promote living well with an implantable cardioverter defibrillator: Insights from a pilot project.

Objective: To evaluate a pilot education program designed to improve patients' experience of living well with an implantable cardioverter-defibrillator (ICD).

Methods: Patient Partners with previously implanted ICD and clinicians collaboratively performed monthly education sessions for potential and recent ICD recipients. Curriculum development was informed by current evidence of ICD patients' unique educational needs; delivery format transitioned to a virtual platform following the onset of COVID-19.

Exploring the implementation and evaluation of a distributed leadership model within a Scottish, integrated health and care context.

Background: Health and care systems are facing unprecedented challenges, exacerbated by wicked issues that have no single solution and are complex to solve. It has recently been suggested that how such systems are structured (ie, in hierarchies) may not be the most effective approach to tackling these issues. Increasing calls have been made for senior leaders within these systems to adopt structures that emphasise leadership as a distributed endeavour as an approach to foster greater collaboration and enhance innovation.

Imatinib Resistance in Chronic Myeloid Leukemia Associated with a D363G Kinase Domain Mutation.

Acquired resistance to tyrosine kinase inhibitors (TKIs) remains a therapeutic challenge in the treatment of chronic myeloid leukemia (CML). The most studied reason for TKI resistance is the acquisition of mutations within the tyrosine kinase domain (KDM) and of which the majority of which occur at seven codons within this region. A case of CML is described in which presence of a rare D363G KDM resulted in a suboptimal response to frontline imatinib.

Gene-Folic Acid Interactions and Risk of Conotruncal Heart Defects: Results from the National Birth Defects Prevention Study.

Conotruncal heart defects (CTDs) are heart malformations that affect the cardiac outflow tract and typically cause significant morbidity and mortality. Evidence from epidemiological studies suggests that maternal folate intake is associated with a reduced risk of heart defects, including CTD. However, it is unclear if folate-related gene variants and maternal folate intake have an interactive effect on the risk of CTDs.

The functional health needs of older persons in custody: A rapid review.

Introduction: The number of older persons in custody is increasing and older incarcerated individuals have higher functional healthcare needs and higher healthcare costs. Consideration of available measures and interventions to address functional decline, are therefore imperative given the importance of disability to healthcare spending.

Purpose: To identify the existing literature describing the functional health needs of older incarcerated individuals.

Interfacility Transfer Guidelines for Isolated Facial Trauma: A Multidisciplinary Expert Consensus.

Background: The objective of this study was to develop guidelines for the transfer of patients with isolated craniomaxillofacial trauma.

Methods: A national, multidisciplinary expert panel was assembled from leadership in national organizations and contributors to published literature on facial reconstruction. The final panel consisted of five plastic surgeons, four otolaryngologist-head and neck surgeons, and four oral and maxillofacial surgeons.

Investigating racial bias within Australian rules football commentary.

International research has shown that live sports commentary exhibits racial bias. Specifically, non-White players are more likely to be praised in terms of their physicality, while White players are more likely to be praised in terms of their intellect and character. The current study, which utilised a quantitative content analysis design, examined whether the speech of AFL commentators exhibited racial bias.

The Effects of Rearing in a Shelved Environment on Behavioral and Physiological Markers of Welfare in Rats (Rattus norvegicus).

Early-life experiences are critical modifiers of development. An important component of early-life experience is the nature of maternal interactions, which can be modified by stress. During rearing, mothers are typically allocated to single-level cages where they are readily accessible to pups, a potentially stressful scenario not reflective of nature.

The assessment of competency and coercion in the End of Life Choice Act 2019.

The eligibility criteria of the End of Life Choice Act 2019 specify the person must be competent to make an informed decision about assisted dying. The patient must initiate the conversation about assisted dying, and then it is incumbent on health professionals to perform a skilled exploration of the person's suffering and rationale. The legal standards for competence must be met.

The gain of function SCN1A disorder spectrum: novel epilepsy phenotypes and therapeutic implications.

Brain voltage-gated sodium channel NaV1.1 (SCN1A) loss-of-function variants cause the severe epilepsy Dravet syndrome, as well as milder phenotypes associated with genetic epilepsy with febrile seizures plus. Gain of function SCN1A variants are associated with familial hemiplegic migraine type 3.

Effect of excess weight and insulin resistance on DNA methylation in prepubertal children.

Epigenetic mechanisms, such as DNA methylation, regulate gene expression and play a role in the development of insulin resistance. This study evaluates how the BMI z-score (BMIz) and the homeostatic model assessment of insulin resistance (HOMA-IR), alone or in combination, relate to clinical outcomes and DNA methylation patterns in prepubertal children. DNA methylation in peripheral blood mononuclear cells (PBMCs) and clinical outcomes were measured in a cohort of 41 prepubertal children.