Infarctive encephalopathy in zoo-housed gibbons in North America.

Progressive neurologic signs without a known underlying etiology have been observed in managed gibbon populations housed at institutions in North America. In 2018, the Gibbon Species Survival Plan initiated a veterinary survey to evaluate clinical histories among gibbons displaying neurologic signs. The clinical results of this survey as well as the results of a centralized histologic review of brain samples from 5 species of managed gibbons displaying neurologic signs are outlined here.

Lessons learned from conducting a serological survey for Japanese encephalitis after detecting the first cases in New South Wales, Australia, 2022.

Problem: The first known locally acquired cases of Japanese encephalitis virus (JEV) infection in New South Wales (NSW), Australia, were identified in March 2022. NSW Health (the state entity for health care in NSW), with its partner agencies, conducted a serological survey to identify the prevalence of JEV antibody responses in high-risk communities in NSW.

Context: JEV infection is rare in Australia; therefore, vaccination is not recommended for the majority of Australians.

Analysis of invasive group A streptococcal puerperal sepsis in Calgary, Alberta: clinical consequences and policy implications.

We analyzed invasive group A streptococcal puerperal sepsis cases in a large health zone in Alberta, Canada between 2013 and 2022. Of the 21 cases, 85.7% were adjudicated as hospital/delivery-acquired, with 2 clusters having identical isolates found through whole genome sequencing.

Spermidine metabolism regulates leukemia stem and progenitor cell function through KAT7 expression in patient-derived mouse models.

Acute myeloid leukemia (AML) is a devastating disease initiated and maintained by a rare subset of cells called leukemia stem cells (LSCs). LSCs are responsible for driving disease relapse, making the development of new therapeutic strategies to target LSCs urgently needed. The use of mass spectrometry-based metabolomics profiling has enabled the discovery of unique and targetable metabolic properties in LSCs.

An output-null signature of inertial load in motor cortex.

Coordinated movement requires the nervous system to continuously compensate for changes in mechanical load across different conditions. For voluntary movements like reaching, the motor cortex is a critical hub that generates commands to move the limbs and counteract loads. How does cortex contribute to load compensation when rhythmic movements are sequenced by a spinal pattern generator? Here, we address this question by manipulating the mass of the forelimb in unrestrained mice during locomotion.

RNA binding protein-directed control of leukemic stem cell evolution and function.

Strict control over hematopoietic stem cell decision making is essential for healthy life-long blood production and underpins the origins of hematopoietic diseases. Acute myeloid leukemia (AML) in particular is a devastating hematopoietic malignancy that arises from the clonal evolution of disease-initiating primitive cells which acquire compounding genetic changes over time and culminate in the generation of leukemic stem cells (LSCs). Understanding the molecular underpinnings of these driver cells throughout their development will be instrumental in the interception of leukemia, the enabling of effective treatment of pre-leukemic conditions, as well as the development of strategies to target frank AML disease.

Epigenetic regulation of noncanonical menin targets modulates menin inhibitor response in acute myeloid leukemia.

Menin inhibitors that disrupt the menin-MLL interaction hold promise for treating specific acute myeloid leukemia (AML) subtypes, including those with KMT2A rearrangements (KMT2A-r), yet resistance remains a challenge. Here, through systematic chromatin-focused CRISPR screens, along with genetic, epigenetic, and pharmacologic studies in a variety of human and mouse KMT2A-r AML models, we uncovered a potential resistance mechanism independent of canonical menin-MLL targets. We show that a group of noncanonical menin targets, which are bivalently cooccupied by active menin and repressive H2AK119ub marks, are typically downregulated after menin inhibition.

Central Venous Pressure and Impaired Renal Function in Children and Young Adults With Cardiovascular Disease.

Background: Traditionally, low cardiac output has been considered the primary hemodynamic driver of renal function and injury. Adult data suggest that central venous pressure (CVP) is a more important factor.

Objectives: The authors hypothesized that in children with cardiovascular disease, higher CVP predicts lower estimated glomerular filtration rate (eGFR) and worsening renal function (WRF).

Achieving Enteral Autonomy in Children with Intestinal Failure Following Inpatient Admission: A Case Series.

We describe cases of intestinal failure wherein inpatient admission was critical toward enteral autonomy. We performed a retrospective chart review of 6 children with long-term parenteral nutrition dependence who were weaned from parenteral nutrition after admission. Admissions included feeding and medication titration, interdisciplinary care, and a home parenteral nutrition team consultation.

FOUND Trial: randomised controlled trial study protocol for case finding of obstructive sleep apnoea in primary care using a novel device.

Introduction: Obstructive sleep apnoea (OSA) is a common, but underdiagnosed, sleep disorder. If untreated, it leads to poor health outcomes, including Alzheimer's disease, cancer, cardiovascular disease and all-cause mortality. Our aim is to determine the feasibility and cost-effectiveness of moving the testing for OSA into general practice and how general practitioner (GP)-based screening affects overall detection rates.

Cardiomyopathy, an uncommon phenotype of congenital disorders of glycosylation: Recommendations for baseline screening and follow-up evaluation.

Introduction: Congenital disorders of glycosylation (CDG) are a continuously expanding group of monogenic disorders that disrupt glycoprotein and glycolipid biosynthesis, leading to multi-systemic manifestations. These disorders are categorized into various groups depending on which part of the glycosylation process is impaired. The cardiac manifestations in CDG can significantly differ, not only across different types but also among individuals with the same genetic cause of CDG.

The seroprevalence of antibodies to Japanese encephalitis virus in five New South Wales towns at high risk of infection, 2022: a cross-sectional serosurvey.

Objectives: To determine the proportion of people in New South Wales towns at high risk of Japanese encephalitis virus (JEV) infections during the 2022 outbreak; to identify risk factors for JEV infection.

Study Design: Cross-sectional serosurvey study of the seroprevalence of JEV-specific antibodies in NSW.

Setting, Participants: Convenience sample of people (all ages) from five regional NSW towns deemed to be at high risk of JEV infections after first outbreak of Japanese encephalitis in southeastern Australia in early 2022 (Balranald, Corowa, Dubbo, Griffith, Temora), 21 June - 22 July 2022.

Diet management in congenital diarrheas and enteropathies - general concepts and disease-specific approach, a narrative review.

Congenital diarrheas and enteropathies (CODE) are a group of rare, heterogenous, monogenic disorders that lead to chronic diarrhea in infancy. Definitive treatment is rarely available, and supportive treatment is the mainstay. Nutritional management in the form of either specialized formulas, restrictive diet, or parenteral nutrition support in CODE with poor enteral tolerance is the cornerstone of CODE treatment and long-term growth.

Carotid body dysregulation contributes to Long COVID symptoms.

Background: The symptoms of long COVID, which include fatigue, breathlessness, dysregulated breathing, and exercise intolerance, have unknown mechanisms. These symptoms are also observed in heart failure and are partially driven by increased sensitivity of the carotid chemoreflex. As the carotid body has an abundance of ACE2 (the cell entry mechanism for SARS-CoV-2), we investigated whether carotid chemoreflex sensitivity was elevated in participants with long COVID.

Clinical Presentation, Classification, and Outcomes of Cardiogenic Shock in Children.

Background: Despite growing cardiogenic shock (CS) research in adults, the epidemiology, clinical features, and outcomes of children with CS are lacking.

Objectives: This study sought to describe the epidemiology, clinical presentation, hospital course, risk factors, and outcomes of CS among children hospitalized for acute decompensated heart failure (ADHF).

Methods: We examined consecutive ADHF hospitalizations (<21 years of age) from a large single-center retrospective cohort.

An output-null signature of inertial load in motor cortex.

Coordinated movement requires the nervous system to continuously compensate for changes in mechanical load across different contexts. For voluntary movements like reaching, the motor cortex is a critical hub that generates commands to move the limbs and counteract loads. How does cortex contribute to load compensation when rhythmic movements are clocked by a spinal pattern generator? Here, we address this question by manipulating the mass of the forelimb in unrestrained mice during locomotion.

The psychological impact of the COVID-19 pandemic and the role of resilience: cross cultural differences between Brazil, Italy, and the United States.

Objective: Restrictive measures consequent to the COVID-19 pandemic have had a significant psychological impact on everyday life in the general population, even though differences between countries remain poorly investigated. The present study sought to examine the different psychological impacts and resilience of the pandemic among three of the most heavily hit countries: Brazil, Italy, and the United States.

Methods: This cross-sectional study separately involved three national community populations, namely the Brazilian, the Italian, and the American population.

Domiciliary transcutaneous electrical stimulation in patients with obstructive sleep apnoea and limited adherence to continuous positive airway pressure therapy: a single-centre, open-label, randomised, controlled phase III trial.

Background: Hypoglossal nerve stimulation (HNS) for obstructive sleep apnoea (OSA) is a novel way to manage the condition. We hypothesised that in patients with OSA and limited adherence to continuous positive airway pressure (CPAP) therapy, domiciliary transcutaneous electrical stimulation (TESLA) would control sleep apnoea and provide health benefits.

Methods: We undertook a single-centre, open-label, randomised, controlled phase III trial in patients with OSA (apnoea-hypopnoea-index [AHI] 5-35 h), a BMI of 18.

Single-centre, single-blinded, randomised, parallel group, feasibility study protocol investigating if mandibular advancement device treatment for obstructive sleep apnoea can reduce nocturnal gastro-oesophageal reflux (MAD-Reflux trial).

Introduction: Just under half of patients with obstructive sleep apnoea (OSA) also have gastro-oesophageal reflux disease (GORD). These conditions appear to be inter-related and continual positive airway pressure (CPAP) therapy, the gold standard treatment for OSA to prevent airway collapse, has been shown to reduce GORD. As the impact of mandibular advancement devices, a second-line therapy for OSA, on GORD has yet to be investigated, a feasibility study is needed prior to a definitive trial.

Persistent Salmonella enterica serovar Typhi sub-populations within host interrogated by whole genome sequencing and metagenomics.

Salmonella enterica serovar Typhi (S. Typhi) causes typhoid fever and, in some cases, chronic carriage after resolution of acute disease. This study examined sequential isolates of S.

Atypical infiltrates on endomyocardial biopsy are associated with adverse outcomes in pediatric heart transplantation.

Background: The significance of atypical infiltrates (eosinophils or plasma cells) on endomyocardial biopsy (EMB) after pediatric heart transplant (HTx) is not known. We hypothesized that atypical infiltrates are associated with worse post-HTx outcomes.

Methods: We performed a retrospective cohort study of consecutive patients <21 years old who underwent primary HTx between 2013 and 2017.

Embedding Aboriginal cultural governance, capacity, perspectives and leadership into a local Public Health Unit Incident Command System during COVID-19 in New South Wales, Australia.

This case study describes the development and implementation of a governance structure that prioritised First Nations peoples in a local public health Incident Command System activated for the COVID-19 pandemic response in New South Wales, Australia. Using lessons learnt from past pandemics and planning exercises, public health leaders embedded an approach whereby First Nations peoples determined and led community and culturally informed pandemic control strategies and actions.In March 2020, First Nations governance was embedded into the local public health emergency response to COVID-19 in the Hunter New England region of New South Wales, Australia, enabling First Nations staff and community members to actively participate in strategic and operational decision-making with the objective of minimising COVID-19-related risks to First Nations peoples and communities.

Ventilatory Efficiency Is Reduced in People With Hypertension During Exercise.

Background An elevated ventilatory efficiency slope during exercise (minute ventilation/volume of expired CO; V/VCO slope) is a strong prognostic indicator in heart failure. It is elevated in people with heart failure with preserved ejection, many of whom have hypertension. However, whether the V/VCO slope is also elevated in people with primary hypertension versus normotensive individuals is unknown.

External assessment and refinement of a population pharmacokinetic model to guide tacrolimus dosing in pediatric heart transplant.

Study Objective: The immunosuppressant tacrolimus is a first-line agent to prevent graft rejection following pediatric heart transplant; however, it suffers from extensive inter-patient variability and a narrow therapeutic window. Personalized tacrolimus dosing may improve transplant outcomes by more efficiently achieving and maintaining therapeutic tacrolimus concentrations. We sought to externally validate a previously published population pharmacokinetic (PK) model that was constructed with data from a single site.