BACKGROUND Timely and safe elective health care facilitates return to normal activities for patients and prevents emergency admissions. Surgery is a cornerstone of elective care and relies on complex pathways. This study aimed to take a whole-system approach to evaluating access to and quality of elective health care globally, using inguinal hernia as a tracer condition. METHODS This was a prospective, international, cohort study conducted between Jan 30 and May 21, 2023, in which any hospital performing inguinal hernia repairs was eligible to take part. Consecutive patients of any age undergoing primary inguinal hernia repair were included. A measurement set mapped to the attributes of WHO's Health System Building Blocks was defined to evaluate access (emergency surgery rates, bowel resection rates, and waiting times) and quality (mesh use, day-case rates, and postoperative complications). These were compared across World Bank income groups (high-income, upper-middle-income, lower-middle-income, and low-income countries), adjusted for hospital and country. Factors associated with postoperative complications were explored with a three-level multilevel logistic regression model. FINDINGS 18 058 patients from 640 hospitals in 83 countries were included, of whom 1287 (7·1%) underwent emergency surgery. Emergency surgery rates increased from high-income to low-income countries (6·8%, 9·7%, 11·4%, 14·2%), accompanied by an increase in bowel resection rates (1·2%, 1·4%, 2·3%, 4·2%). Overall waiting times for elective surgery were similar around the world (median 8·0 months from symptoms to surgery), largely because of delays between symptom onset and diagnosis rather than waiting for treatment. In 14 768 elective operations in adults, mesh use decreased from high-income to low-income countries (97·6%, 94·3%, 80·6%, 61·0%). In patients eligible for day-case surgery (n=12 658), day-case rates were low and variable (50·0%, 38·0%, 42·1%, 44·5%). Complications occurred in 2415 (13·4%) of 18 018 patients and were more common after emergency surgery (adjusted odds ratio 2·06, 95% CI 1·72-2·46) and bowel resection (1·85, 1·31-2·63), and less common after day-case surgery (0·39, 0·34-0·44). INTERPRETATION This study demonstrates that elective health care is essential to preventing over-reliance on emergency systems. We identified actionable targets for system strengthening: clear referral pathways and increasing mesh repair in lower-income settings, and boosting day-case surgery in all income settings. These measures might strengthen non-surgical pathways too, reducing the burden on society and health services. FUNDING NIHR Global Health Research Unit on Global Surgery and Portuguese Hernia and Abdominal Wall Society (Sociedade Portuguesa de Hernia e Parede Abdominal).

Diagnosing intracardiac masses poses a complex, multimodal challenge. We present the case of a 72-year-old woman with a history of rheumatic fever leading to mitral stenosis and a previous mitral valve commissurotomy who reported fatigue, weakness, and palpitations over the past three months. Echocardiography revealed a tumor (53 × 40 mm) in the enlarged left atrium, attached by a wide base to the left atrium wall, exhibiting variable densities. Computerized tomography identified a heterodense mass (53 × 46 × 37 mm) with similar attachments. Angiography showed two branches from the circumflex artery intricately associated with the mass. Despite unsuccessful embolization of the mass’ blood supply, surgical intervention including mitral valve replacement, tricuspid valve annuloplasty, and tumor removal was pursued. Pathohistological analysis confirmed the mass as a thrombus. During the postoperative follow-up, the patient presented with no complaints. Follow-up echocardiography indicated the normal function of the mechanical mitral valve prosthesis and the absence of intracardiac masses. While it remains unknown whether this neovascularization is specific to patients with severe mitral valve disease, this case highlights the diagnostic challenges of differentiating between thrombi and tumors in the context of mitral valve disease. It illustrates the critical role of multimodal imaging in elucidating the anatomical and functional relationships within the heart, thereby guiding accurate diagnosis and effective treatment.

Background and Purpose Posterior cerebral artery occlusion (PCAo) can cause long-term disability, yet randomized controlled trials to guide optimal reperfusion strategy are lacking. We compared the outcomes of PCAo patients treated with endovascular thrombectomy (EVT) with or without intravenous thrombolysis (IVT) to patients treated with IVT alone. Methods From the multicenter retrospective Posterior cerebraL ArTery Occlusion (PLATO) registry, we included patients with isolated PCAo treated with reperfusion therapy within 24 hours of onset between January 2015 and August 2022. The primary outcome was the distribution of the modified Rankin Scale (mRS) at 3 months. Other outcomes comprised 3-month excellent (mRS 0–1) and independent outcome (mRS 0–2), early neurological improvement (ENI), mortality, and symptomatic intracranial hemorrhage (sICH). The treatments were compared using inverse probability weighted regression adjustment. Results Among 724 patients, 400 received EVT+/-IVT and 324 IVT alone (median age 74 years, 57.7% men). The median National Institutes of Health Stroke Scale score on admission was 7, and the occluded segment was P1 (43.9%), P2 (48.3%), P3–P4 (6.1%), bilateral (1.0%), or fetal posterior cerebral artery (0.7%). Compared to IVT alone, EVT+/-IVT was not associated with improved functional outcome (adjusted common odds ratio [OR] 1.07, 95% confidence interval [CI] 0.79–1.43). EVT increased the odds for ENI (adjusted OR [aOR] 1.49, 95% CI 1.05–2.12), sICH (aOR 2.87, 95% CI 1.23–6.72), and mortality (aOR 1.77, 95% CI 1.07–2.95). Conclusion Despite higher odds for early improvement, EVT+/-IVT did not affect functional outcome compared to IVT alone after PCAo. This may be driven by the increased risk of sICH and mortality after EVT.

Conditioning before allogeneic hematopoietic stem cell transplantation (AlloHSCT) increases the tissue injury signal IL-33 in fibroblastic reticular cells (FRC). Released IL-33 directly stimulates donor CD4 T cells to prime IL-12-independent Type 1 T helper cell (Th1) differentiation and expansion. Tissue stroma upregulates IL-33, but a role for IL-33 in sustaining the pathogenic donor Th1 responses causing GVHD is unclear. We compared B6 mice with inducible ST2 deletion (R26-CreERT2xSt2fl/fl) to wildtype (WT) R26-CreERT2 as T cell donors in a lethal GVHD model (B6 to BALB/c). Donor ST2 deletion at days 10-14 post AlloHSCT increased CD4 T cells Foxp3 expression with reciprocal decreases in Tbet expression in both the lymphoid organs and target tissues. Sustained IL-33 signaling also maintained donor T cell TCF1 expression. Ablating ST2 after GVHD development improved clinical scores and promoted recipient weight gain. How bioactive IL-33 is released from nuclear sequestration remains undefined. RNAseq analysis suggested that IL-33 stimulates T cell granzyme B (GzmB) expression and B6 GzmB deficient (Gzmb-/-) donor T cells displayed reduced activation and expansion similar to ST2 deficient CD4 T cells. In contrast to GzmBWT, anti-IL-33 antibodies had no impact on GzmBKO T cell responses. Thus, cross-talk between donor T cells and IL-33+ stroma orchestrates the T cell identities that are critical to sustain the pathogenic CD4 T cell responses causing GVHD.

Due to their advantages—longer internal force delay compared to bulk materials, resistance to harsh conditions, damping of a wide frequency spectrum, insensitivity to ambient temperature, high reliability and low cost—granular materials are seen as an opportunity for the development of high-performance, lightweight vibration-damping elements (particle dampers). The performance of particle dampers is affected by numerous parameters, such as the base material, the size of the granules, the flowability, the initial prestress, etc. In this work, a series of experiments were performed on specimens with different combinations of influencing parameters. Energy-based design parameters were used to describe the overall vibration-damping performance. The results provided information for a deeper understanding of the dissipation mechanisms and their mutual correlation, as well as the influence of different parameters (base material, granule size and flowability) on the overall damping performance. A comparison of the performance of particle dampers with carbon steel and polyoxymethylene granules and conventional rubber dampers is given. The results show that the damping performance of particle dampers can be up to 4 times higher compared to conventional bulk material-based rubber dampers, even though rubber as a material has better vibration-damping properties than the two granular materials in particle dampers. However, when additional design features such as mass and stiffness are introduced, the results show that the overall performance of particle dampers with polyoxymethylene granules can be up to 3 times higher compared to particle dampers with carbon steel granules and conventional bulk material-based rubber dampers.

Introduction: Taekwondo has developed into an Olympic sport, which means that a thorough understanding of the main Taekwondo athletes and competitors' characteristics is necessary. This study investigated the fundamental anthropometric measurements of high-level Taekwondo athletes, with a particular focus on disparities between genders. The objective of this study was to assess and contrast the physical attributes of elite Taekwondo athletes, specifically examining the differences between males and females. Methods: A group of 28 highly skilled Taekwondo athletes, consisting of 14 female and 14 male cadets participated in this study. Results: The results showed a significant difference between male and female competitors' anthropometric variables, most notably in skinfold thickness and fat tissue proportion (p≤ 0.01). Conclusion: Accordingly, these data can help taekwondo specialists in the early stages of selection, especially when advanced examinations are impossible. Further studies profiling this group of responders should include more characteristics to help practitioners recognize talents and create training program goals.

U ovom radu bavimo se nuđenjem usluga koje bi inteligentna javna uprava mogla nuditi svim korisnicima određenih usluga. Ovdje predlažemo primjenu elektroničkih i mobilnih usluga u javnoj upravi te korištenje nekih novih koncepata koji mogu podržati takvu uslugu. Također ćemo navesti čega se trebaju pridržavati i korisnik usluga i javna uprava u realizaciji koncepta nuđenja usluga korištenjem računala, tableta i mobilnih uređaja. Navest ćemo ključne elemente koji se moraju uzeti u obzir pri implementaciji inteligentne javne uprave i nuđenju usluga te što je sve potrebno da bi nova javna uprava nudila usluge, a što je korisniku potrebno za primanje usluga elektroničkim ili mobilnim putem (em-Services). U radu ćemo prikazati rezultate istraživanja o zadovoljstvu korisnika uslugama javne uprave i korištenju novih tehnologija u javnoj upravi koje je provedeno od 1. 10. 2022. do 31. 12. 2022. godine.

Preliminary studies demonstrated beneficial effects of dietary creatine across different post-viral fatigue syndromes. Creatine is often co-administered with glucose to improve its potency yet whether glucose boost the efficacy of creatine in long COVID remains currently unknown. In this report, we investigate the effects of 8-wk creatine intake with and without glucose on patient-reported outcomes, exercise tolerance, and tissue creatine levels in patients with long COVID. Fifteen male and female long COVID adult patients (age 39.7±16.0 y; 9 women) with moderate fatigue and at least one of additional long COVID-related symptoms volunteered to participate in this randomized controlled parallel-group interventional trial. All patients were allocated in a double-blind parallel-group design (1 : 1 : 1) to receive creatine (8 g of creatine monohydrate per day), a mixture of creatine and glucose (8 g of creatine monohydrate and 3 g of glucose per day), or placebo (3 g of glucose per day) t.i.d. during an 8-wk intervention interval. Two-way ANOVA with repeated measures (treatment vs. time interaction) revealed significant differences in changes in total creatine levels between the groups, showing an interaction effect at two brain locations (right precentral white matter F=34.740, p=0.008; partial η2=0.72; left paracentral grey matter F=19.243, p=0.019; partial η2=0.88), with creatine and creatine-glucose outcompeted placebo to elevate creatine levels at these two locations. Several long COVID symptoms (including body aches, breathing problems, difficulties concentrating, headache, and general malaise) were significantly reduced in creatine-glucose group at 8-wk follow-up (p≤0.05); the effect sizes for reducing body aches, difficulties concentrating, and headache were 1.33, 0.80, and 1.12, respectively, suggesting a large effect of creatine-glucose mixture for these outcomes. Our preliminary findings suggest that supplying exogenous creatine with glucose could be recommended as an effective procedure in replenishing brain creatine pool and alleviating long COVID features in this prevalent condition.

Commensal rats are highly adaptable to coexisting with human populations, often relying on human dwellings and immediate access to food, water, shelter and space. We present the case of an adult commensal brown rat, Rattus norvegicus, that was found in an urban area of Sarajevo (Bosnia and Herzegovina). Histopathological examination revealed numerous eggs of Calodium hepaticum in the liver parenchyma and coprological examination identified species of the class Cestoda (Rodentolepis spp., Hymenolepis diminuta) and the class Nematoda (Trichuris muris, Nippostrongylus brasiliensis and Strongyloides ratti). Haematological parameter analysis was conducted using the “Idexx ProCyte Dx” cell counter and biochemical parameters of the rat's serum were tested. Haematocrit, haemoglobin content and erythrocyte indices (MCV, MCH) were decreased and moderate quantities of spherocytes were present (4.95 %). The total number of leukocytes was within the physiological range, with minimally increased values of monocytes and neutrophils and decreased values of eosinophils. The results of the morphometric examinations were in the expected range for adult rats. This case report highlights the public health risk posed by commensal rats if systematic rodent control measures are not fully implemented. It should serve as a guide for future research on the population of commensal rats in the cities of Bosnia and Herzegovina, aimed at a detailed identification of parasitic zoonotic pathogens.

Cyclotides are a diverse class of plant-derived cyclic, disulfide-rich peptides with a unique cyclic cystine knot topology. Their remarkable structural stability and resistance to proteolytic degradation can lead to improved pharmacokinetics and oral activity as well as selectivity and high enzymatic stability. Thus, cyclotides have emerged as powerful scaffold molecules for designing peptide-based therapeutics. The chemical engineering of cyclotides has generated novel peptide ligands of G protein-coupled receptors (GPCRs), today's most exploited drug targets. However key challenges potentially limit the widespread use of cyclotides in molecular grafting applications. Folding of cyclotides containing bioactive epitopes remains a major bottleneck in cyclotide synthesis. Here we present a modular ‘plug and play’ approach that effectively bypasses problems associated with the oxidative folding of cyclotides. By grafting onto a pre-formed acyclic cyclotide-like scaffold we show that difficult-to-graft sequences can be easily obtained and can target GPCRs with nanomolar affinities and potencies. We further show the suitability of this new method to graft other complex epitopes including structures with additional disulfide bonds that are not readily available via currently employed chemical methods, thus fully unlocking cyclotides to be used in drug design applications.