Comorbidities reduce survival and quality of life in COPD with severe lung hyperinflation.

Rationale And Aim: Patients with COPD often present with a significant number of comorbidities, which are thought to be related to a higher mortality risk. Our aim was to investigate the prevalence and impact of comorbidities on survival and quality of life (QoL), specifically in patients with emphysema characterised by severe lung hyperinflation.

Patients And Methods: Data were prospectively collected from patients who visited our hospital for evaluating their eligibility for a bronchoscopic lung volume reduction treatment and were included in the Groningen Severe COPD cohort (NCT04023409).

Convergent evolution links molybdenum insertase domains with organism-specific sequences.

In all domains of life, the biosynthesis of the pterin-based Molybdenum cofactor (Moco) is crucial. Molybdenum (Mo) becomes biologically active by integrating into a unique pyranopterin scaffold, forming Moco. The final two steps of Moco biosynthesis are catalyzed by the two-domain enzyme Mo insertase, linked by gene fusion in higher organisms.

Highlights from the 11th Bronchitis International Symposium: "Heterogeneity of Lung Disease in a Changing Environment," Groningen, The Netherlands, 2024.

This meeting report provides an overview of the highlights of the Bronchitis XI international symposium, held in June 2024 in Groningen, The Netherlands. The theme of this year's symposium was "heterogeneity of lung disease in a changing environment," and the symposium contained five different sessions focused on (i) heterogeneity of chronic lung disease, (ii) environmental changes with impact on lung disease, (iii) the aging lung, (iv) bronchitis, and (v) innovative therapy. The highlights from each of these sessions will be discussed separately, providing an overview of latest studies, new data, and enthralling discussions.

Managing Pediatric Asthma Exacerbations: The Role of Timely Systemic Corticosteroid Administration in Emergency Care Settings-A Multicentric Retrospective Study.

Background: Asthma is the most prevalent chronic respiratory condition in children. An asthma exacerbation (AE) is a frequent reason for emergency department (ED) visits. An important step in the management of a moderate to severe AE is the administration of systemic corticosteroids (SCS) within 1 h after ED presentation.

Does anti-HPA-1a affect birthweight in fetal and neonatal alloimmune thrombocytopenia?

Background: Fetal and neonatal alloimmune thrombocytopenia (FNAIT) ensues from parental incompatibility for platelet alloantigens with maternal sensitization. HPA-1a/1b incompatibility is the most common cause of FNAIT in Caucasians. Placental villitis and lower birthweight in FNAIT suggest anti-HPA-1a may have effects beyond inducing thrombocytopenia.

Translation and Validation of the Dutch Version of the Sun Exposure and Protection Index.

Introduction: Skin cancer is currently the most common cancer type worldwide, and numbers are rapidly increasing. To improve primary prevention, individualised prevention strategies may be of interest as this enhances the chance of long-term behavioural change. The Sun Exposure and Protection Index (SEPI), previously validated in multiple languages, is a tool that could help identify individuals with risky behaviour and tailor interventions to the person's propensity to change.

Efficacy and Safety of Tildrakizumab in Older Patients: Pooled Analyses of Two Randomized Phase III Clinical Trials (reSURFACE 1 and reSURFACE 2) Through 244 Weeks.

The evidence on treating older patients with psoriasis with modern biologics is scarce. This study compared the efficacy and safety of tildrakizumab among younger and older patients with psoriasis (< 65/≥ 65 years) in a post hoc analysis of 2 phase III trials (reSURFACE1/2, n = 1,862). Tildrakizumab 100 mg/200 mg was administered at weeks 0/4/every 12 weeks thereafter.

Safety Assessment of Conventional and Biological Systemic Therapy in Older Adults with Psoriasis, a Real-world Multicentre Cohort Study.

Optimal selection of systemic therapy in older adults with psoriasis can be challenging, due to sparse evidence-based guidance. This multicentre retrospective study investigated the safety of systemic therapy with causality assessment in a real-world cohort of older adults (≥ 65 years) with psoriasis. Data from 6 hospitals on (serious) adverse events were collected, causality assessment performed and incidence rate ratios calculated.

Drug Survival, Safety, and Effectiveness of Biologics in Older Patients with Psoriasis: A Comparison with Younger Patients-A BioCAPTURE Registry Study.

Background: Psoriasis is a common inflammatory disease in any age group, but also in older patients (≥ 65 years of age). Since older patients are often excluded from clinical trials, limited data specifically on this growing population are available, e.g.

Age-based treatment differences in and reluctance to treating older adults with systemic antipsoriatic therapy - a mixed-method pilot study.

Background: Evidence-based guidance in older adults (≥65 years) with psoriasis is sparse and undertreatment might be present.

Objectives: To assess prescribing patterns, comfort levels, barriers and needs of dermatologists when treating older adults with systemic antipsoriatic therapy.

Methods: A mixed-methods design was used including a survey among all Dutch dermatologists and residents, followed by semi-structured interviews.

Dolichocolon Presenting with Bilateral Hydronephrosis in a Neonate.

Background: Dolichocolon is an inborn anatomic variant of the colon with redundancies often causing constipation and/or volvulus presenting in childhood, adolescence, or adulthood. To the best of our knowledge, this is the first case of dolichocolon presenting in infancy with constipation and bilateral hydronephrosis. .

Bronchiolitis in COVID-19 times: a nearly absent disease?

Stay-at-home orders, physical distancing, face masks and other non-pharmaceutical interventions (NPIs) do not only impact COVID-19, but also the dynamics of various other infectious diseases. Bronchiolitis is a clinically diagnosed viral infection of the lower respiratory tract, and causes a yearly seasonal wave of admissions in paediatric wards worldwide. We counted 92,5% less bronchiolitis hospitalisations in Antwerp before the expected end of the peak this year (of which only 1 RSV positive), as compared to the last 3 years.

Disease and Treatment Characteristics in Geriatric Psoriasis: A Patient Survey Comparing Age Groups.

Little is known about psoriasis in geriatric patients, whereas treating this growing population can be challenging due to comorbidities, comedication and physical impairments. To compare disease and treatment characteristics of psoriasis patients ≥ 65 years old with patients < 65 years old, a self-assessment survey was sent to all members of the Dutch Psoriasis Association (n = 3,310). In total, 985 (29.

Clinimetric properties of the Glasgow Health Status Inventory, Glasgow Benefit Inventory, Peak Nasal Inspiratory Flow, and 4-Phase Rhinomanometry in adults with nasal obstruction.

Background: The validity of many measurement instruments frequently used in rhinology is unknown. This study describes clinimetric properties of well-known subjective and objective outcomes, i.e.

The hide and seek of Plasmodium vivax in West Africa: report from a large-scale study in Beninese asymptomatic subjects.

Background: Plasmodium vivax is considered to be absent from western Africa, where the prevalence of Duffy-negative red blood cell phenotype proves to be high. Several studies have, however, detected P. vivax infection cases in this part of Africa, raising the question of what is the actual prevalence of P.

Fragment-Based Discovery of Dual JC Virus and BK Virus Helicase Inhibitors.

There are currently no treatments for life-threatening infections caused by human polyomaviruses JCV and BKV. We therefore report herein the first crystal structure of the hexameric helicase of JCV large T antigen (apo) and its use to drive the structure-based design of dual JCV and BKV ATP-competitive inhibitors. The crystal structures obtained by soaking our early inhibitors into the JCV helicase allowed us to rapidly improve the biochemical activity of our inhibitors from 18 μM for the early 6-(2-methoxyphenyl)- and the 6-(2-ethoxyphenyl)-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazole hits 1a and 1b to 0.

Severe acute kidney injury as presentation of Burkitt's lymphoma.

We discuss a case of acute kidney injury (AKI) at a very young age caused by primary lymphomatous renal infiltration due to Burkitt's lymphoma and analyse the literature on this rare condition. At presentation, clinical examination showed impressive bilateral nephromegaly and hypertension. Blood analysis indicated severe AKI, mild anaemia and normal serum electrolytes.

Insights into regioselective metabolism of mefenamic acid by cytochrome P450 BM3 mutants through crystallography, docking, molecular dynamics, and free energy calculations.

Cytochrome P450 BM3 (CYP102A1) mutant M11 is able to metabolize a wide range of drugs and drug-like compounds. Among these, M11 was recently found to be able to catalyze formation of human metabolites of mefenamic acid and other nonsteroidal anti-inflammatory drugs (NSAIDs). Interestingly, single active-site mutations such as V87I were reported to invert regioselectivity in NSAID hydroxylation.

The ears of the African elephant: unexpected high seroprevalence of Plasmodium ovale and Plasmodium malariae in healthy populations in Western Africa.

Background: Malaria Is A Life-Threatening Pathology In Africa. Plasmodium Falciparum And Plasmodium Vivax Attract The Most Focus Because Of Their High Prevalence And Mortality. Knowledge About The Prevalence Of The Cryptic Pathogens Plasmodium Ovale And Plasmodium Malariae Is Limited.

Simulation in medical school education: review for emergency medicine.

Medical education is rapidly evolving. With the paradigm shift to small-group didactic sessions and focus on clinically oriented case-based scenarios, simulation training has provided educators a novel way to deliver medical education in the 21st century. The field continues to expand in scope and practice and is being incorporated into medical school clerkship education, and specifically in emergency medicine (EM).

Crystal structure of the ectodomain complex of the CGRP receptor, a class-B GPCR, reveals the site of drug antagonism.

Dysregulation of the calcitonin gene-related peptide (CGRP), a potent vasodilator, is directly implicated in the pathogenesis of migraine. CGRP binds to and signals through the CGRP receptor (CGRP-R), a heterodimer containing the calcitonin receptor-like receptor (CLR), a class B GPCR, and RAMP1, a receptor activity-modifying protein. We have solved the crystal structure of the CLR/RAMP1 N-terminal ectodomain heterodimer, revealing how RAMPs bind to and potentially modulate the activities of the CLR GPCR subfamily.

3-Aryl-4-(arylhydrazono)-1H-pyrazol-5-ones: Highly ligand efficient and potent inhibitors of GSK3beta.

A series of 3-aryl-4-(arylhydrazono)-1H-pyrazol-5-one inhibitors of GSK3beta was developed from a low molecular weight, highly ligand efficient screening hit 1. Hit-to-lead optimization led to a number of highly potent inhibitors, while maintaining the high ligand efficiency of the screening hit.