Objective: High blood pressure and proteinuria play major roles in chronic kidney disease (CKD), a high-mortality condition that affects millions of people. Reactive oxygen species (ROS) produced by NADPH oxidases are implicated in many pathophysiological processes including hypertension and CKD. Apocynin (APO) shows the anti-oxidative activity by inhibiting the assembly of NADPH oxidase and overproduction of ROS. The aim of this study was to investigate the effects of apocynin on oxidative stress, blood pressure and kidney function in normotensive rats with CKD induced by 5/6 nephrectomy through ligation of renal poles (Nx-L). Design and method: Male Wistar rats were divided into three groups. One group was control (sham surgery) and two other groups underwent two-step surgical procedure of 5/6 nephrectomy induced by ligation of renal poles. Unlike conventional Nx which leads to high mortality due to hemorrhage in or after surgery, here we induced Nx by ligation of the upper and lower poles (leads to necrosis of these poles) of left kidney after removal the right kidney one week later. After 4 weeks from this procedure, control and model group (Nx-L) received vehicle, while Nx-L+APO received apocynin 20 mg/kg/day (i.p.) for 4-week-period. Mean blood pressure (MAP), proteinuria, and oxidative stress marker (thiobarbituric acid reactive species-TBARS) in plasma and urine were measured. Results: In model group we observed significantly increased MAP (121,13±2,01vs.94,88±4,13mmHg, p<0.001), plasma creatinine (55,4±1,3vs. 41,3±2,3μmol/l, p<0.001), and proteinuria (0,036±0,006vs.0,017±0,001mg/min/kg, p<0.01) levels compared to those in control. Furthermore, significant increase of plasma TBARS level (5,47±0,77vs.2,75±0,52nmol/ml, p<0.01) and urine TBARS excretion (1,10±0,06vs.0,86±0,04nmol/min/kg, p<0.01) were detected in model compared to control. Interestingly, APO treatment significantly reduced blood pressure to the level of control (83,88±5,14vs.94,88±4,13mmHg). APO significantly reduced urine protein loss (0,024±0,002vs.0,036±0,006mg/min/kg, p<0.05) and plasma creatinine level (49,9±1,5vs.55,4±1,3μmol/l, p<0.05) as well as reduced plasma lipid peroxidation (2,19±0,26vs.5,47±0,77nmol/ml, p<0.001) in comparison to model group. Conclusions: Our results show that APO treatment prevents blood pressure rising and ameliorates kidney function in rats with 5/6 nephrectomy trough improvement of systemic oxidative status. Therefore, NADPH oxidase presents a potential therapeutic target in this form of kidney disease.

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).

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.

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.

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.

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.

Pathological data showed focal inflammation and regions of diffuse neuronal loss in the cortex of people with multiple sclerosis (MS). In this work, we applied a novel model (“soma and neurite density imaging (SANDI)”) to multishell diffusion-weighted MRI data acquired in healthy subjects and people with multiple sclerosis (pwMS), in order to investigate inflammation and degeneration-related changes in the cortical tissue of pwMS. We aimed to (i) establish whether SANDI is applicable in vivo clinical data; (ii) investigate inflammatory and degenerative changes using SANDI soma fraction (fsoma)—a marker of cellularity—in both cortical lesions and in the normal-appearing-cortex and (iii) correlate SANDI fsoma with clinical and biological measures in pwMS. We applied a simplified version of SANDI to a clinical scanners. We then provided evidence that pwMS exhibited an overall decrease in cortical SANDI fsoma compared to healthy subjects, suggesting global degenerative processes compatible with neuronal loss. On the other hand, we have found that progressive pwMS showed a higher SANDI fsoma in the outer part of the cortex compared to relapsing–remitting pwMS, possibly supporting current pathological knowledge of increased innate inflammatory cells in these regions. A similar finding was obtained in subpial lesions in relapsing–remitting patients, reflecting existing pathological data in these lesion types. A significant correlation was found between SANDI fsoma and serum neurofilament light chain—a biomarker of inflammatory axonal damage—suggesting a relationship between SANDI soma fraction and inflammatory processes in pwMS again. Overall, our data show that SANDI fsoma is a promising biomarker to monitor changes in cellularity compatible with neurodegeneration and neuroinflammation in the cortex of MS patients.

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.

Abstract: Surgical correction of inguinal hernias is the most commonly used surgical procedure in the world. Currently only three surgical techniques have been validated, that is the Shouldice technique, the Lichtenstein technique, and laparoscopic techniques such as transabdominal preperitoneal (TAPP) hernioplasty and totally extraperitoneal endoscopic hernioplasty (TEP).The aim of the study: The aim of this study is to show the results in terms of postoperative recovery, complications, length of hospitalization after inguinal hernia surgery in patients who underwent the Lichtenstein and the laparoscopic (TAPP) methods.Material and methods: This is a monocentric, retrospective cohort study, conducted in the period from 2019 to 2023. The research period covered 70 patients who underwent surgery at the Clinic for General and Abdominal Surgery with Glandular Surgery, of the University Clinical Center, Sarajevo. The patients were divided into two groups: Group 1: 20 patients who underwent the TAPP method and Group 2: 50 patients who underwent the Lichtenstein method. All patients underwent surgery performed by two doctors.Results: One woman (1.4%) and 69 men (98.6%) participated in the research. Of the total number, 50 patients (72.5%) were treated with the Lichtenstein technique, and 19 (27.5%) were treated with the TAPP technique (p=0.539). The statistical results did not show a significant difference in the average age between patients who underwent the Lichtenstein and the TAPP technique (T=0.759; p=0.450).Discussion: There was no significant difference in relation to age and type of surgery (T=0.759; p=0.450). There was no statistical difference in the choice of surgical approach in relation to the laterality of the hernia (P<0.001), nor any statistically significant difference between the TAPP and Lichtenstein surgical procedures in relation to BMI T=0.613; p=0.542. Our analyses showed that patients treated with the TAPP technique had a statisticallysignificantly higher probability of shorter postoperative hospitalization compared to those treated with the Lichtenstein technique (B=0.245; p=0.019). Two patients in the study had complications within 30 days (Clavien-Dindo Grade I and Grade IIIB).Conclusion: Using an individual approach for each patient, surgical treatment of hernia using laparoscopic TAPP can be the first choice in patients without comorbidities, without previous pelvic surgery, bilaterality or recurrence of previous surgery (anterior approach). Patients treated with the laparoscopic technique (TAPP) have a shorter hospitalization time, which ultimately affects the economic aspect.

Thyrostats are a group of forbidden substances in food producing animals that increase water absorption in muscle tissue and the gastrointestinal tract of animals. These substances can be abused as illegal growth promoters as oral drugs on farms before slaughtering. The consequences of their illegal use on farm animals include higher yield though inferior meat quality, while these substances also pose a potential risk to human health, and so their application is banned in European Union Member States. Thiouracil (2-thiouracil) (TU) is the representative, and belongs to the group of thyrostats but also can be naturally present in the urine of farm animals fed with feed containing Brassicaceae species. The aim of this study was to monitor TU concentrations in pig and bovine urine in the period from 2015 to 2023. For this purpose, 391 urine samples were collected as a part of the National Residue Control Plan (NRCP) and TU concentrations were determined by liquid chromatography tandem mass spectrometry. TU was detected in 89 of 391 samples, or 22.76%. TU concentration ranged from 1.66 to 28.30 μg/L, and a statistically significant difference (P < 0.05) was determined in urine TU concentrations between pigs and bovines. Mean concentrations of TU varied by year, and ranged from 1.66 to 8.06 μg/L in pig urine and from 5.92 to 13.68 μg/L in bovine urine. None of the analysed urine samples contained TU concentration in excess of 30 μg/L, which is the cut-off value to distinguish potentially natural origin resulting from a cruciferous diet (Brassicaceae species). The results exclude the possibility of abuse of this substances in the livestock industry in the Republic of Croatia.

Inflammatory bowel disease (IBD), encompassing Crohn’s disease (CD) and ulcerative colitis (UC), necessitates effective management strategies. This study aims to evaluate the real-world efficacy of vedolizumab, a newer biological therapy, in treating IBD in Bosnia and Herzegovina. A retrospective observational study was conducted across six medical centers, involving 139 IBD patients, 76 with UC and 63 with CD. Patients were assessed for clinical remission and other outcomes at the 26-week mark post vedolizumab treatment initiation. At 26 weeks, clinical remission was achieved in 82.9% of UC patients and 85.7% of CD patients. Mucosal healing was observed in 38.1% of CD patients. The efficacy of vedolizumab did not significantly differ based on prior anti-tumor necrosis factor (anti-TNF) exposure. Notably, the clinical scoring tools for predicting vedolizumab response showed limited applicability in this cohort. Vedolizumab demonstrated high efficacy in treating both UC and CD in real-world settings in Bosnia and Herzegovina, underscoring its potential as a significant therapeutic option in IBD management.

Simple Summary The manual measurement of ablation zones (AZs) in radiofrequency ablation (RFA) therapy is prone to inaccuracies, highlighting the need for automated methods. Our study investigated the effectiveness of an Artificial Intelligence (AI) model, Mask2Former, in automating AZ measurements from ultrasound images, comparing its performance against manual techniques. Conducted on chicken breast and liver samples, the study found the AI model to achieve high accuracy, particularly in chicken breast tissue, with no significant difference in measurements between AI and manual methods. These results suggest that the Mask2Former model can significantly reduce variability in manual measurements, marking a step forward in the automation of AZ measurement in RFA therapy research and potentially improving the precision of treatment assessments. Abstract Background: The accurate delineation of ablation zones (AZs) is crucial for assessing radiofrequency ablation (RFA) therapy’s efficacy. Manual measurement, the current standard, is subject to variability and potential inaccuracies. Aim: This study aims to assess the effectiveness of Artificial Intelligence (AI) in automating AZ measurements in ultrasound images and compare its accuracy with manual measurements in ultrasound images. Methods: An in vitro study was conducted using chicken breast and liver samples subjected to bipolar RFA. Ultrasound images were captured every 15 s, with the AI model Mask2Former trained for AZ segmentation. The measurements were compared across all methods, focusing on short-axis (SA) metrics. Results: We performed 308 RFA procedures, generating 7275 ultrasound images across liver and chicken breast tissues. Manual and AI measurement comparisons for ablation zone diameters revealed no significant differences, with correlation coefficients exceeding 0.96 in both tissues (p < 0.001). Bland–Altman plots and a Deming regression analysis demonstrated a very close alignment between AI predictions and manual measurements, with the average difference between the two methods being −0.259 and −0.243 mm, for bovine liver and chicken breast tissue, respectively. Conclusion: The study validates the Mask2Former model as a promising tool for automating AZ measurement in RFA research, offering a significant step towards reducing manual measurement variability.