α-Ketoglutarate dehydrogenase is a therapeutic vulnerability in acute myeloid leukemia.

Perturbations in intermediary metabolism contribute to the pathogenesis of acute myeloid leukemia (AML) and can produce therapeutically actionable dependencies. Here, we probed whether alpha-ketoglutarate (aKG) metabolism represents a specific vulnerability in AML. Using functional genomics, metabolomics, and mouse models, we identified the aKG dehydrogenase complex, which catalyzes the conversion of aKG to succinyl CoA, as a molecular dependency across multiple models of adverse-risk AML.

Impact of Convulsive Maternal Seizures on Fetus Dynamics.

The study findings demonstrate that the amniotic fluid plays an important role in protecting the fetus during convulsive maternal seizures. The amniotic fluid was found to be an effective buffer, significantly reducing the transfer of kinetic energy to the fetus during these events. This highlights the sufficient protection provided by the amniotic fluid in such circumstances.

A Safety-Centric Study on the Use of Inflatable Abdominal Binders for Managing Orthostatic Hypotension.

The study focuses on the design and evaluation of inflatable abdominal binders for managing Orthostatic Hypotension. Orthostatic hypotension is a condition characterized by a significant drop in blood pressure when a person stands up, leading to symptoms such as dizziness, lightheadedness, and even fainting. The management of orthostatic hypotension typically involves a combination of pharmacological and non-pharmacological strategies.

iPSC-Derived LCHADD Retinal Pigment Epithelial Cells Are Susceptible to Lipid Peroxidation and Rescued by Transfection of a Wildtype AAV-HADHA Vector.

Purpose: Progressive choroid and retinal pigment epithelial (RPE) degeneration causing vision loss is a unique characteristic of long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency (LCHADD), a fatty acid oxidation disorder caused by a common c.1528G>C pathogenic variant in HADHA, the α subunit of the mitochondrial trifunctional protein (TFP). We established and characterized an induced pluripotent stem cell (iPSC)-derived RPE cell model from cultured skin fibroblasts of patients with LCHADD and tested whether addition of wildtype (WT) HAHDA could rescue the phenotypes identified in LCHADD-RPE.

Biomechanical Effects of Seizures on Cerebral Dynamics and Brain Stress.

Epilepsy is one of the most common neurological disorders globally, affecting about 50 million people, with nearly 80% of those affected residing in low- and middle-income countries. It is characterized by recurrent seizures that result from abnormal electrical brain activity, with seizures varying widely in manifestation. The exploration of the biomechanical effects that seizures have on brain dynamics and stress levels is relevant for the development of more effective treatments and protective strategies.

A G1528C Hadha knock-in mouse model recapitulates aspects of human clinical phenotypes for long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency.

Long chain 3-hydroxyacyl-CoA dehydrogenase deficiency (LCHADD) is a fatty acid oxidation disorder (FAOD) caused by a pathogenic variant, c.1528 G > C, in HADHA encoding the alpha subunit of trifunctional protein (TFPα). Individuals with LCHADD develop chorioretinopathy and peripheral neuropathy not observed in other FAODs in addition to the more ubiquitous symptoms of hypoketotic hypoglycemia, rhabdomyolysis and cardiomyopathy.

Continuous Positive Airway Pressure plus Mandibular Advancement Therapy (PAPMAT): study protocol for an adaptive randomised crossover trial comparing the benefits and costs of combining two established treatments for obstructive sleep apnoea.

Background: Obstructive sleep apnoea (OSA) involves repeated breathing pauses during sleep due to upper airway obstruction. It causes excessive daytime sleepiness and has other health impacts. Continuous positive airway pressure (CPAP) therapy is effective first line treatment for moderate to severe OSA.

Assessment of Abdominal Constrictor's Forces for Informing Computational Models of Orthostatic Hypotension.

Orthostatic hypotension is defined as a sudden drop in blood pressure upon standing from a sitting or supine position. The prevalence of this condition increases exponentially with age. Nonpharmacological treatments are always the first step in the management of this condition, such as the use of an abdominal constriction belt to optimize the blood volume in the abdomen.

Manipulating the microbiome alters regenerative outcomes in Xenopus laevis tadpoles via lipopolysaccharide signalling.

Xenopus laevis tadpoles can regenerate functional tails, containing the spinal cord, notochord, muscle, fin, blood vessels and nerves, except for a brief refractory period at around 1 week of age. At this stage, amputation of the tadpole's tail may either result in scarless wound healing or the activation of a regeneration programme, which replaces the lost tissues. We recently demonstrated a link between bacterial lipopolysaccharides and successful tail regeneration in refractory stage tadpoles and proposed that this could result from lipopolysaccharides binding to Toll-like receptor 4 (TLR4).

A Multi-Site Qualitative Study Examining Pharmacy Student Perspectives on the Opioid Crisis.

To determine pharmacy students' perspectives regarding opioid use, the opioid crisis, and pharmacy education related to both topics. Students from each professional year at eight participating schools and colleges of pharmacy were invited to participate in focus groups and answer questions about their experiences with the opioid crisis. Faculty and/or staff moderated the focus groups and audio-recorded responses.

A literature survey of all volatiles from healthy human breath and bodily fluids: the human volatilome.

This paper comprises an updated version of the 2014 review which reported 1846 volatile organic compounds (VOCs) identified from healthy humans. In total over 900 additional VOCs have been reported since the 2014 review and the VOCs from semen have been added. The numbers of VOCs found in breath and the other bodily fluids are: blood 379, breath 1488, faeces 443, milk 290, saliva 549, semen 196, skin 623 and urine 444.

Transmission of Severe Acute Respiratory Syndrome Coronavirus 2 during Border Quarantine and Air Travel, New Zealand (Aotearoa).

The strategy in New Zealand (Aotearoa) to eliminate coronavirus disease requires that international arrivals undergo managed isolation and quarantine and mandatory testing for severe acute respiratory syndrome coronavirus 2. Combining genomic and epidemiologic data, we investigated the origin of an acute case of coronavirus disease identified in the community after the patient had spent 14 days in managed isolation and quarantine and had 2 negative test results. By combining genomic sequence analysis and epidemiologic investigations, we identified a multibranched chain of transmission of this virus, including on international and domestic flights, as well as a probable case of aerosol transmission without direct person-to-person contact.

Genomic Evidence of In-Flight Transmission of SARS-CoV-2 Despite Predeparture Testing.

Since the first wave of coronavirus disease in March 2020, citizens and permanent residents returning to New Zealand have been required to undergo managed isolation and quarantine (MIQ) for 14 days and mandatory testing for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). As of October 20, 2020, of 62,698 arrivals, testing of persons in MIQ had identified 215 cases of SARS-CoV-2 infection. Among 86 passengers on a flight from Dubai, United Arab Emirates, that arrived in New Zealand on September 29, test results were positive for 7 persons in MIQ.

Civilian Ballistic Tibia Shaft Fractures Compared With Blunt Tibia Shaft Fractures: Open or Closed?

Objectives: To identify a group of ballistic tibia fractures, report the outcomes of these fractures, and compare them with both closed and open tibia fractures sustained by blunt mechanisms. We hypothesized that ballistic tibia fractures and blunt open fractures would have similar outcomes.

Design: Retrospective cohort study.

CASPA (CArdiac Sarcoidosis in PApworth) improving the diagnosis of cardiac involvement in patients with pulmonary sarcoidosis: protocol for a prospective observational cohort study.

Introduction: Sarcoidosis is a multisystem disease, predominantly affecting the lungs but can involve the heart, resulting in cardiac sarcoidosis (CS). Patients require MRI/Positron Emission Tomography (PET) scans for diagnosis. Echocardiography, ECG and Holter monitoring may be indicative but not diagnostic alone.

Quality, scope and reporting standards of randomised controlled trials in Irish Health Research: an observational study.

Background: Despite efforts to improve the accuracy and transparency of the design, conduct, and reporting of randomised controlled trials (RCTs), deficiencies remain. Such deficiencies contribute to significant, avoidable waste of health research investment and impede reproducibility. This study aimed to synthesise and critically analyse changes over time in the conduct and reporting of internationally published evidence on patient and/or population health-oriented RCTs conducted in one country.

Physiological response, function of sweat glands, and hair follicle cycling in cattle in response to fescue toxicosis and hair genotype.

Fescue toxicosis is a syndrome that results when cattle consume toxic endophyte-infected tall fescue. The objective of this study was to compare the response in physiological variables, sweat gland function, hair follicle cycling, and gene expression to feeding a total mixed ration that included tall fescue haylage and tall fescue seed containing a toxic endophyte (EI) or tall fescue haylage containing a nontoxic novel endophyte (EN) in beef heifers (Angus × Senepol heifers, n = 31) with 2 different hair genotypes. Numbers in each subgroup were as follows: novel endophyte, heterozygous slick (EN-S; n = 8), novel endophyte, homozygous hairy (wild type, EN-W; n = 7), endophyte-infected, heterozygous slick (EI-S; n = 10), and endophyte-infected, homozygous hairy (wild type, EI-W; n = 6).

Early Host Interactions That Drive the Dysregulated Response in Sepsis.

Sepsis is defined as life-threatening organ dysfunction caused by a dysregulated host response to infection. While many individual cells and systems in the body are involved in driving the excessive and sometimes sustained host response, pathogen engagement with endothelial cells and platelets early in sepsis progression, are believed to be key. Significant progress has been made in establishing key molecular interactions between platelets and pathogens and endothelial cells and pathogens.

Design and students' perceptions of a virtually facilitated outpatient pharmacy practice laboratory course.

Background And Purpose: Web conferencing, interactive video conferencing, and classroom and lecture capture are widely used in pharmacy education. This study aimed to determine student pharmacists' receptiveness to a virtually facilitated outpatient pharmacy practice laboratory course.

Educational Activity And Setting: A new course design was implemented for a first-year (P1) laboratory course utilizing Zoom, an internet-based "cloud" video and chat conference room, for communication across two campuses.

Corrosion of carbon steel and the passivating properties of corrosion films formed under high-PT geothermal conditions.

Corrosion is a major obstacle to a safe implementation of geotechnical applications. Using a novel approach that includes vertical scanning interferometry (VSI) and electrochemical impedance spectroscopy (EIS) we discuss time-dependent carbon steel corrosion and film formation at geothermally relevant temperatures (80-160 °C) in CO-saturated mildly acidic NaCl brine. Iron dissolution kinetics follows a logarithmic rate at 80 and 160 °C and a linear rate at 120 °C.

Impact of slick hair trait on physiological and reproductive performance in beef heifers consuming ergot alkaloids from endophyte-infected tall fescue1.

Fescue toxicosis is a multifaceted syndrome common in cattle grazing endophyte-infected tall fescue. The objective of this study was to evaluate the impact of the slick hair trait on physiological and reproductive parameters in heifers experiencing fescue toxicosis. Angus × Senepol heifers (n = 31) were blocked by weight (393.