Reactive and potentially toxic cofactors such as copper ions are imported into eukaryotic cells and incorporated into target proteins by unknown mechanisms. Atx1, a prototypical copper chaperone protein from yeast, has now been shown to act as a soluble cytoplasmic copper(I) receptor that can adopt either a two- or three-coordinate metal center in the active site. Atx1 also associated directly with the Atx1-like cytosolic domains of Ccc2, a vesicular protein defined in genetic studies as a member of the copper-trafficking pathway. The unusual structure and dynamics of Atx1 suggest a copper exchange function for this protein and related domains in the Menkes and Wilson disease proteins.

Metal ion chaperone function of the soluble Cu(I) receptor Atx1.

Science

Eosinophilic granulomatosis with polyangiitis (EGPA) is a rare anti-neutrophil cytoplasmic antibody&#xa0;(ANCA)-associated vasculitis, characterized by asthma, eosinophilia and granulomatous or vasculitic involvement of several organs. The diagnosis and management of EGPA are often challenging and require an integrated, multidisciplinary approach. Current practice relies on recommendations and guidelines addressing the management of ANCA-associated vasculitis and not specifically developed for EGPA. Here, we present evidence-based, cross-discipline guidelines for the diagnosis and management of EGPA that reflect the substantial advances that have been made in the past few years in understanding the pathogenesis, clinical subphenotypes and differential diagnosis of the disease, as well as the availability of new treatment options. Developed by a panel of European experts on the basis of literature reviews and, where appropriate, expert opinion, the 16 statements and five overarching principles cover the diagnosis and staging, treatment, outcome and follow-up of EGPA. These recommendations are primarily intended to be used by healthcare professionals, pharmaceutical industries and drug regulatory authorities, to guide clinical practice and decision-making in EGPA. These guidelines are not intended to limit access to medications by healthcare agencies, nor to impose a fixed order on medication use.

Evidence-Based Guideline for the diagnosis and management of eosinophilic granulomatosis with polyangiitis.

Nature Reviews. Rheumatology

The objective of this review is to discuss acid-base physiology, describe the essential steps for interpreting an arterial blood gas and relevant laboratory tests, and review the 4 distinct types of acid-base disorders.

A comprehensive literature search and resultant bibliography review of PubMed from inception through March 7, 2023.

Relevant English-language articles were extracted and evaluated.

Critically ill patients are prone to significant acid-base disorders that can adversely affect clinical outcomes. Assessing these acid-base abnormalities can be complex because of dynamic aberrations in plasma proteins, electrolytes, extracellular volume, concomitant therapies, and use of mechanical ventilation. This article provides a systematic approach to acid-base abnormalities which is necessary to facilitate prompt identification of acid-base disturbances and prevent untoward morbidity and mortality.

Many acid-base disorders result from medication therapy or are treated with medications. Pharmacists are uniquely poised as the medication experts on the multidisciplinary team to assist with acid-base assessments in the context of pharmacotherapy.

The use of a systematic approach to address acid-base disorders can be performed by all pharmacists to improve pharmacotherapy and optimize patient outcomes.

A Systematic Approach to Understanding Acid-Base Disorders in the Critically Ill.

Annals of Pharmacotherapy

Heart failure (HF) is a complex clinical syndrome involving structural and/or functional abnormalities of the heart. Heart failure is often classified based on left ventricular ejection fraction, which serves as a predictor of mortality. The majority of the data supporting disease-modifying pharmacological therapies are from patients with reduced ejection fraction (less than 40%). However, with the recent results from the sodium glucose cotransporter-2 inhibitor trials, there is renewed interest in identifying potential beneficial pharmacological therapies. This review focuses on and includes pharmacological HF therapies across the spectrum of ejection fraction, providing an overview of the novel trials. We also examined the effects of the treatments on mortality, hospitalization, functional status, and biomarker levels to further investigate the interplay between ejection fraction and HF.

Practical Pharmacological Treatment of Heart Failure: Does Ejection Fraction Matter Anymore?

Journal of Cardiovascular Development and Disease

Infarction (MINOCA) and ischaemia (INOCA) with non-obstructive coronary disease are recent non-conventional presentations of coronary syndromes that are increasingly recognised in the clinical arena, particularly with the availability of new cardiovascular imaging techniques. Both are related to heart failure (HF). MINOCA is not associated with benign outcomes, and HF is among the most prevalent events. Regarding INOCA, microvascular dysfunction has also been found to associate with HF, particularly with preserved ejection fraction (HFpEF).

Regardless of the several aetiologies underlying HF in MINOCA, it is likely related to LV dysfunction, where secondary prevention is not yet clearly established. Regarding INOCA, coronary microvascular ischaemia has been associated to endothelial dysfunction leading ultimately to diastolic dysfunction and HFpEF. MINOCA and INOCA are clearly related to HF. In both, there is a lack of studies on the identification of the risk factors for HF, diagnostic workup and, importantly, the appropriate primary and secondary prevention strategies.

MINOCA and INOCA: Role in Heart Failure.

Current Heart Failure Reports

Polycystic ovary syndrome (PCOS) is a complex and heterogeneous disorder that commonly affects women in the reproductive age group. The disorder has features that propose a blend of functional reproductive disorders, such as anovulation and hyperandrogenism, and metabolic disorders, such as hyperglycemia, hypertension, and obesity in women. Until today, the three implemented groups of criteria for the diagnosis of PCOS are from the National Institutes of Health (NIH) in the 1990s, Rotterdam 2003, and the Androgen Excess Polycystic Ovary Syndrome 2009 criteria. Currently, the most widely utilized criteria are the 2003 Rotterdam criteria, which validate the diagnosis of PCOS with the incidence of two out of the three criteria: hyperandrogenism (clinical and/or biochemical), irregular cycles, and polycystic ovary morphology. Currently, the anti-M&#xfc;llerian hormone in serum is introduced as a substitute for the follicular count and is controversially emerging as an official polycystic ovarian morphology/PCOS marker. In adolescents, the two crucial factors for PCOS diagnosis are hyperandrogenism and irregular cycles. Recently, artificial intelligence, specifically machine learning, is being introduced as a promising diagnostic and predictive tool for PCOS with minimal to zero error that would help in clinical decisions regarding early management and treatment. Throughout this review, we focused on the pathophysiology, clinical features, and diagnostic challenges in females with PCOS.

Polycystic Ovary Syndrome: Pathophysiology and Controversies in Diagnosis.

Diagnostics

The management of acute ischemic stroke has undergone a paradigm shift in the past decade. This has been spearheaded by the emergence of endovascular thrombectomy, along with advances in medical therapy, imaging, and other facets of stroke care. Herein, we present an updated review of the various stroke trials that have impacted and continue to transform stroke management. It is critical for the radiologist to stay abreast of the ongoing developments to provide meaningful input and remain a useful part of the stroke team.

Advances in Acute Ischemic Stroke Treatment: Current Status and Future Directions.

AJNR. American Journal of Neuroradiology

Autoimmune diseases are a diverse group of conditions characterized by aberrant B cell and T cell reactivity to normal constituents of the host. These diseases occur widely and affect individuals of all ages, especially women. Among these diseases, the most prominent immunological manifestation is the production of autoantibodies, which provide valuable biomarkers for diagnosis, classification and disease activity. Although T cells have a key role in pathogenesis, they are technically more difficult to assay. In general, autoimmune disease results from an interplay between a genetic predisposition and environmental factors. Genetic predisposition to autoimmunity is complex and can involve multiple genes that regulate the function of immune cell populations. Less frequently, autoimmunity can result from single-gene mutations that affect key regulatory pathways. Infection seems to be a common trigger for autoimmune disease, although the microbiota can also influence pathogenesis. As shown in seminal studies, patients may express autoantibodies many years before the appearance of clinical or laboratory signs of disease - a period called pre-clinical autoimmunity. Monitoring autoantibody expression in at-risk populations may therefore enable early detection and the initiation of therapy to prevent&#xa0;or attenuate tissue damage. Autoimmunity may not be static, however, and remission can be achieved by some patients treated with current agents.

Metal ion chaperone function of the soluble Cu(I) receptor Atx1.

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Metal ion chaperone function of the soluble Cu(I) receptor Atx1.

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