The Wilms tumor gene WT1, a proposed tumor suppressor gene, has been identified based on its location within a homozygous deletion found in tumor tissue. The gene encodes a putative transcription factor containing a Cys/His zinc finger domain. The critical homozygous deletions, however, are rarely seen, suggesting that in many cases the gene may be inactivated by more subtle alterations. To facilitate the search for smaller deletions and point mutations we have established the genomic organization of the WT1 gene and have determined the sequence of all 10 exons and flanking intron DNA. The pattern of alternative splicing in two regions has been characterized in detail. These results will form the basis for future studies of mutant alleles at this locus.

The genomic organization and expression of the WT1 gene.

Genomics

The proportion of the elderly population continues to increase due to the global increase in longevity. Heart failure with preserved ejection fraction (HFpEF) is common in the elderly due to cellular aging, myocardial stiffness, and multiple comorbidities. This age group is often under-represented in clinical trials. In this narrative review, we looked into the latest evidence-based lines of management of HFpEF in this vulnerable cohort. In this narrative review, we brought the latest evidence on the treatment of HFpEf in the elderly. We searched the largest three scientific databases (Pubmed, Google Scholar, and EMBASE) using the&#xa0;search words (elderly, HFpEF, heart failure with preserved ejection fraction, guidelines, treatment, and management) in different combinations. To date, screening for and treatment of the causes of HFpEF (such as hypertension, coronary artery disease [CAD], valvular heart disease, and cardiac amyloidosis) and associated comorbidities (such as diabetes mellitus [DM], iron deficiency, obesity, and thyroid dysfunction) are the main line of management of HFpEF. A multidisciplinary team, including an HF specialist cardiologist, an HF nurse, a geriatrician, a dietician, a psychologist, a physiotherapist, and an occupational therapist, should manage HFpEF elderly patients. Other specialist input may be needed according to the patient's requirements. The evidence on the effective management of HFpEF in the elderly age group is scarce and controversial. Some studied non-pharmacological approaches include supervised exercise training, pulmonary artery pressure monitoring, and the interatrial shunt device (an emerging modality that includes a small percutaneously inserted interatrial left to right valve aiming to reduce the left atrial and pulmonary wedge pressures). These modalities can only improve the symptoms and HF hospitalizations without robustly impacting cardiovascular (CV) death. Among the pharmacological approaches to treat HFpEF, only the sodium-glucose cotransporter 2 (SGLT-2) inhibitors proved efficacy in reducing the hard outcomes of CV death, HF hospitalizations, and urgent visits for HF when used in elderly HFpEF patients, irrespective of the presence of diabetes mellitus. Diuretics are only beneficial to alleviate the symptoms of fluid overload, with a risk of renal impairment in volume-depleted patients. The evidence on the effectiveness of other HF-specific disease-modifying agents in elderly HFpEF patients is controversial. Elderly patients have a higher risk of having side effects from HF medications due to the higher prevalence of polypharmacy, cognitive decline, and impairment of kidney and liver functions. Therefore, cautious initiation of HF treatment with a close follow-up of the blood pressure, liver functions, kidney functions, and electrolytes are of utmost importance.

Management of Heart Failure With Preserved Ejection Fraction in Elderly Patients: Effectiveness and Safety.

Curēus

Since the publication of the EULAR recommendations for the management of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) in 2016, several randomised clinical trials have been published that have the potential to change clinical care and support the need for an update.

Using EULAR standardised operating procedures, the EULAR task force undertook a systematic literature review and sought opinion from 20 experts from 16 countries. We modified existing recommendations and created new recommendations.

Four overarching principles and 17 recommendations were formulated. We recommend biopsies and ANCA testing to assist in establishing a diagnosis of AAV. For remission induction in life-threatening or organ-threatening AAV, we recommend a combination of high-dose glucocorticoids (GCs) in combination with either rituximab or cyclophosphamide. We recommend tapering of the GC dose to a target of 5&#x2009;mg prednisolone equivalent/day within 4-5&#x2009;months. Avacopan may be considered as part of a strategy to reduce exposure to GC in granulomatosis with polyangiitis (GPA) or microscopic polyangiitis (MPA). Plasma exchange may be considered in patients with rapidly progressive glomerulonephritis. For remission maintenance of GPA/MPA, we recommend rituximab. In patients with relapsing or refractory eosinophilic GPA, we recommend the use of mepolizumab. Azathioprine and methotrexate are alternatives to biologics for remission maintenance in AAV.

In the light of recent advancements, these recommendations provide updated guidance on AAV management. As substantial data gaps still exist, informed decision-making between physicians and patients remains of key relevance.

EULAR recommendations for the management of ANCA-associated vasculitis: 2022 update.

Annals of the Rheumatic Diseases

Non-alcoholic fatty liver disease (NAFLD) is a serious health problem due to its high incidence and consequences. In view of the existing controversies, new therapeutic options for NAFLD are still being sought. Therefore, the aim of our review was to evaluate the recently published studies on the treatment of NAFLD patients. We searched for articles in the PubMed database using appropriate terms, including "non-alcoholic fatty liver disease", "nonalcoholic fatty liver disease", "NAFLD", "diet", "treatment", "physical activity", "supplementation", "surgery", "overture" and "guidelines". One hundred forty-eight randomized clinical trials published from January 2020 to November 2022 were used for the final analysis. The results show significant benefits of NAFLD therapy associated with the use of not only the Mediterranean but also other types of diet (including low-calorie ketogenic, high-protein, anti-inflammatory and whole-grain diets), as well as enrichment with selected food products or supplements. Significant benefits in this group of patients are also associated with moderate aerobic physical training. The available therapeutic options indicate, above all, the usefulness of drugs related to weight reduction, as well as the reduction in insulin resistance or lipids level and drugs with anti-inflammatory or antioxidant properties. The usefulness of therapy with dulaglutide and the combination of tofogliflozin with pioglitazone should be emphasized. Based on the results of the latest research, the authors of this article suggest a revision of the therapeutic recommendations for NAFLD patients.

What's New in the Treatment of Non-Alcoholic Fatty Liver Disease (NAFLD).

Journal of Clinical Medicine

BTS clinical statement on aspiration pneumonia.

Thorax

Long COVID is an often debilitating illness that occurs in at least 10% of severe acute respiratory syndrome coronavirus&#xa0;2 (SARS-CoV-2) infections. More than 200 symptoms have been identified with impacts on multiple organ systems. At least 65 million individuals worldwide are estimated to have long COVID, with cases increasing daily. Biomedical research has made substantial progress in identifying various pathophysiological changes and risk factors and in characterizing the illness; further, similarities with other viral-onset illnesses such as myalgic encephalomyelitis/chronic fatigue syndrome and postural orthostatic tachycardia syndrome have laid the groundwork for research in the field. In this Review, we explore the current literature and highlight key findings, the overlap with other conditions, the variable onset of symptoms, long COVID in children and the impact of vaccinations. Although these key findings are critical to understanding long COVID, current diagnostic and treatment options are insufficient, and clinical trials must be prioritized that address leading hypotheses. Additionally, to strengthen long COVID research, future studies must account for biases and SARS-CoV-2 testing issues, build on viral-onset research, be inclusive of marginalized populations and meaningfully engage patients throughout the research process.

Long COVID: major findings, mechanisms and recommendations.

Nature Reviews. Microbiology

The current ARDS guidelines highly recommend lung protective ventilation which include plateau pressure (Pplat &#x2009;&lt;&#x2009;30&#xa0;cm H2 O), positive end expiratory pressure (PEEP&#x2009;&gt;&#x2009;5&#xa0;cm H2 O) and tidal volume (Vt of 6&#xa0;ml/kg) of predicted body weight. In contrast, the ELSO guidelines suggest the evaluation of an indication of veno-venous extracorporeal membrane oxygenation (ECMO) due to hypoxemic or hypercapnic respiratory failure or as bridge to lung transplantation. Finally, these recommendations remain a wide range of scope of interpretation. However, particularly patients with moderate-severe to severe ARDS might benefit from strict adherence to lung protective ventilation strategies. Subsequently, we discuss whether extended physiological ventilation parameter analysis might be relevant for indication of ECMO support and can be implemented during the daily routine evaluation of ARDS patients. Particularly, this viewpoint focus on driving pressure and mechanical power.

Mechanical power of ventilation and driving pressure: two undervalued parameters for pre extracorporeal membrane oxygenation ventilation and during daily management?

The genomic organization and expression of the WT1 gene.

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