A Rare Case of Hemophilia: Acquired Factor VIII Deficiency.

Unlike hereditary hemophilia, acquired hemophilia is a rare life-threatening bleeding disorder that occurs in a person who has no personal or family history of bleeding episodes. It usually presents with new-onset subcutaneous/joint/muscle bleeding causing ecchymoses and hematomas, hematuria, GI bleeding, retroperitoneal bleeding, or rarely acute intracranial hemorrhage in elderly individuals. The diagnosis involves assessing prolonged activated partial thromboplastin time (aPTT) and conducting mixing studies after ruling out lupus anticoagulants and interfering substances such as heparins.

Implementation and Evaluation of an End-of-Life Standardized Participant Simulation in an Adult/Gerontology Acute Care Nurse Practitioner Program.

Graduate nursing programs must provide end-of-life (EOL) content to prepare nurse practitioners to manage the holistic needs of patients. This project aimed to measure the End-of-Life Nursing Education Consortium curriculum's impact on student self-confidence and anxiety levels. A pretest/posttest study design was implemented using an EOL simulation and the Nursing Anxiety and Self-Confidence With Clinical Decision-Making Scale (NASC-CDM©) to compare baseline self-confidence and anxiety levels related to clinical decision-making.

Postoperative Packing of Perianal Abscess Cavities (PPAC2): randomized clinical trial.

Background: Perianal abscess is common. Traditionally, postoperative perianal abscess cavities are managed with internal wound packing, a practice not supported by evidence. The aim of this randomized clinical trial (RCT) was to assess if non-packing is less painful and if it is associated with adverse outcomes.

Biochemical and behavioural profile of NTBC treated Tyrosinemie type 1 mice.

Background: Tyrosinemia type 1 (HT1) is a rare metabolic disorder caused by a defect in the tyrosine catabolic pathway. Since HT1 patients are treated with NTBC, outcome improved and life expectancy greatly increased. However extensive neurocognitive and behavioural problems have been described, which might be related to treatment with NTBC, the biochemical changes induced by NTBC, or metabolites accumulating due to the enzymatic defect characterizing the disease.

Trace Oxygen Affects Osmium Redox Polymer Synthesis for Wired Enzymatic Biosensors.

Electrochemical sensors that utilize enzymes are a sensitive, inexpensive means of detecting biologically relevant analytes. These sensors are categorized based on their construction and method of signal transport. Type I sensors consist of a crosslinked enzyme on an electrode surface and are potentially subject to interference from byproducts and other biological analytes.

Risk factors for child stunting in Bangladesh: an analysis using MICS 2019 data.

Background: Malnutrition is considered a major public health challenge and is associated with a range of health issues, including childhood stunting. Stunting is a reliable and well-recognized indicator of chronic childhood malnutrition. The objective of this study is to determine the risk factors associated with stunting among 17,490 children below five years of age in Bangladesh.

Modeling the cognitive effects of diet discontinuation in adults with phenylketonuria (PKU) using pegvaliase therapy in PAH-deficient mice.

Existing phenylalanine hydroxylase (PAH)-deficient mice strains are useful models of untreated or late-treated human phenylketonuria (PKU), as most contemporary therapies can only be initiated after weaning and the pups have already suffered irreversible consequences of chronic hyperphenylalaninemia (HPA) during early brain development. Therefore, we sought to evaluate whether enzyme substitution therapy with pegvaliase initiated near birth and administered repetitively to C57Bl/6-Pah mice would prevent HPA-related behavioral and cognitive deficits and form a model for early-treated PKU. The main results of three reported experiments are: 1) lifelong weekly pegvaliase treatment prevented the cognitive deficits associated with HPA in contrast to persisting deficits in mice treated with pegvaliase only as adults.

Therapeutic liver repopulation by transient acetaminophen selection of gene-modified hepatocytes.

Gene therapy by integrating vectors is promising for monogenic liver diseases, especially in children where episomal vectors remain transient. However, reaching the therapeutic threshold with genome-integrating vectors is challenging. Therefore, we developed a method to expand hepatocytes bearing therapeutic transgenes.

Simulated Learning Experience in Advance Care Planning Conversations.

The Centers for Disease Control and Prevention reports that one-third of all Americans have not done any advance care planning, which is essential for maintaining autonomy when people are no longer able to communicate wishes directly at the end of life. The Institute of Medicine reports that providers have limited training in communication techniques and low confidence in holding advance care planning conversations. Forty-four family nurse practitioner students received classroom communication training using evidence-based end-of-life nursing education consortium materials and role-play opportunities.

Development of a porcine model of phenylketonuria with a humanized R408W mutation for gene editing.

Phenylketonuria (PKU) is a metabolic disorder whereby phenylalanine metabolism is deficient due to allelic variations in the gene for phenylalanine hydroxylase (PAH). There is no cure for PKU other than orthotopic liver transplantation, and the standard of care for patients is limited to dietary restrictions and key amino acid supplementation. Therefore, Pah was edited in pig fibroblasts for the generation of PKU clone piglets that harbor a common and severe human mutation, R408W.

Communications in the time of a pandemic: the readability of documents for public consumption.

Objective: Government communications in a crisis can influence public health outcomes. This research aimed to investigate if written communications of the most commonly sought sources of COVID-19 information available on the internet have readability levels commensurate with those of the general public.

Methods: Online documents from the World Health Organization (WHO), and the governments of Australia, the UK and the US were assessed for readability using an online instrument that calculated scores for the Flesch Reading Ease Score, the SMOG Index and the Readability Consensus Grade Level.

Cardiac tissue citric acid cycle intermediates in exercised very long-chain acyl-CoA dehydrogenase-deficient mice fed triheptanoin or medium-chain triglyceride.

Anaplerotic odd-chain fatty acid supplementation has been suggested as an approach to replenish citric acid cycle intermediate (CACi) pools and facilitate adenosine triphosphate (ATP) production in subjects with long-chain fatty acid oxidation disorders, but the evidence that cellular CACi depletion exists and that repletion occurs following anaplerotic substrate supplementation is limited. We exercised very long-chain acyl-CoA dehydrogenase-deficient (VLCAD-/-) and wild-type (WT) mice to exhaustion and collected cardiac tissue for measurement of CACi by targeted metabolomics. In a second experimental group, VLCAD-/- and WT mice that had been fed chow prepared with either medium-chain triglyceride (MCT) oil or triheptanoin for 4 weeks were exercised for 60 minutes.

A novel Pah-exon1 deleted murine model of phenylalanine hydroxylase (PAH) deficiency.

Phenylalanine hydroxylase (PAH) deficiency, colloquially known as phenylketonuria (PKU), is among the most common inborn errors of metabolism and in the past decade has become a target for the development of novel therapeutics such as gene therapy. PAH deficient mouse models have been key to new treatment development, but all prior existing models natively express liver PAH polypeptide as inactive or partially active PAH monomers, which complicates the experimental assessment of protein expression following therapeutic gene, mRNA, protein, or cell transfer. The mutant PAH monomers are able to form hetero-tetramers with and inhibit the overall holoenzyme activity of wild type PAH monomers produced from a therapeutic vector.

Factors associated with stunting and wasting in children under 2 years in Bangladesh.

Child undernutrition has been a major concern for Bangladesh as it is amongst the highest stunting and wasting prevalent countries in the world. The objective of our study was to explore the socioeconomic determinants of stunting and wasting in children under two years. This study explored nationally representative sample of 7,230 children ranging in age from 0 to <24 months using two separate binary logistic regression models to determine the risk factors associated with child stunting and wasting.

Diabetic Ketoacidosis in Coronavirus Disease Patients With Type 2 Diabetes Mellitus.

The occurrence of diabetes is increasing globally and carries a variety of complications, such as thromboembolism, acute cerebrovascular accidents, and diabetic ketoacidosis (DKA). Although DKA is not commonly associated with type 2 diabetes (T2D), it can manifest in patients who have underlying comorbidities predisposed to DKA. Since the emergence of the coronavirus disease (COVID-19) pandemic, we have seen many cases and studies on the underlying pathophysiology of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pneumonia with or without respiratory failure.

Reducing nosocomial transmission of COVID-19: implementation of a COVID-19 triage system.

Nosocomial transmission of COVID-19 puts patients with other medical problems at risk of severe illness and death. Of 662 inpatients with COVID-19 at an NHS Trust in South London, 45 (6.8%) were likely to have acquired COVID-19 in hospital.

Innovative recruitment and clinical orientation programme to manage NHS junior doctor shortfall: A district hospital experience.

Background: International medical graduates (IMGs) contribute significantly towards the NHS care provision. No standardised clinical orientation programme (COP) for IMGs new to the NHS exists.

Objective: Our objective was to describe recruitment and retention strategies for junior doctors (JDs) in general medicine and develop a framework to anticipate outcomes of these interventions using the realist evaluation methodology.

AAV-Mediated CRISPR/Cas9 Gene Editing in Murine Phenylketonuria.

Phenylketonuria (PKU) due to recessively inherited phenylalanine hydroxylase (PAH) deficiency results in hyperphenylalaninemia, which is toxic to the central nervous system. Restriction of dietary phenylalanine intake remains the standard of PKU care and prevents the major neurologic manifestations of the disease, yet shortcomings of dietary therapy remain, including poor adherence to a difficult and unpalatable diet, an increased incidence of neuropsychiatric illness, and imperfect neurocognitive outcomes. Gene therapy for PKU is a promising novel approach to promote lifelong neurological protection while allowing unrestricted dietary phenylalanine intake.

Socioeconomic correlates of overweight and obesity among ever-married urban women in Bangladesh.

Background: The escalating prevalence of overweight and obesity globally is reflected amongst urban women in many low-to-middle income countries. Evidence also shows that overweight and obesity is an increasing trend in Bangladesh. The present study assessed the prevalence and socioeconomic determinants of overweight and obesity among urban women in Bangladesh.

Purposeful involvement of experts by experience.

Background: There is a growing requirement from professional bodies in the UK that health and social care education must include the voice of experts by experience (EbE). Active steps have been taken at the international level in order to truly embed their involvement. In parallel with this development, there is compounding evidence collated globally that links interprofessional education (IPE) to improved health outcomes.

Tetrahydrobiopterin treatment reduces brain L-Phe but only partially improves serotonin in hyperphenylalaninemic ENU1/2 mice.

Hyperphenylalaninemia (HPA) caused by hepatic phenylalanine hydroxylase (PAH) deficiency has severe consequences on brain monoamine neurotransmitter metabolism. We have studied monoamine neurotransmitter status and the effect of tetrahydrobiopterin (BH) treatment in Pah (ENU1/2) mice, a model of partial PAH deficiency. These mice exhibit elevated blood L-phenylalanine (L-Phe) concentrations similar to that of mild hyperphenylalaninemia (HPA), but brain levels of L-Phe are still ~5-fold elevated compared to wild-type.

Blood phenylalanine reduction corrects CNS dopamine and serotonin deficiencies and partially improves behavioral performance in adult phenylketonuric mice.

Central nervous system (CNS) deficiencies of the monoamine neurotransmitters dopamine and serotonin have been implicated in the pathophysiology of neuropsychiatric dysfunction in human phenylketonuria (PKU). In this study, we confirmed the occurrence of brain dopamine and serotonin deficiencies in association with severe behavioral alterations and cognitive impairments in hyperphenylalaninemic C57BL/6-Pah mice, a model of human PKU. Phenylalanine-reducing treatments, including either dietary phenylalanine restriction or liver-directed gene therapy, initiated during adulthood were associated with increased brain monoamine content along with improvements in nesting behavior but without a change in the severe cognitive deficits exhibited by these mice.