The κ-opioid receptor (KOR) is an attractive target for the development of novel drugs. KOR agonists are potentially safer pain medications, whereas KOR antagonists are promising drug candidates for the treatment of neuropsychiatric disorders. Hitherto, the vast majority of selective drug leads that have been developed for KOR are small molecules. In this study, novel peptide probes were designed by using an endogenous dynorphin A1–13 sequence as a template for peptide stapling via late-stage cysteine functionalization. Leveraging this strategy, we developed a stable and potent KOR antagonist, CSD-CH2(1,8)-NH2, with approximately 1000-fold improved selectivity for KOR over μ- and δ-opioid receptors. Its potent competitive KOR antagonism was verified in KOR-expressing cells, peripheral dorsal root ganglion neurons, and using the tail-flick and rotarod tests in mice. This work highlights the value of cysteine stapling to develop selective peptide probes to modulate central KOR function, as innovative peptide drug candidates for the treatment of KOR-related illnesses.

Background: Although the Bhanja bandavirus (BHAV) is widely distributed in some European countries, human infections are rarely reported. This study analyzed the prevalence of BHAV antibodies in patients with neuroinvasive diseases of unsolved etiology. Methods: A total of 254 Croatian patients who developed neurological symptoms during the four consecutive arbovirus transmission seasons (April 2017–October 2021) were tested. Cerebrospinal fluid (CSF) and urine samples were tested using RT-qPCR. In addition, CSF and serum samples were tested using a virus neutralization test. Results: BHAV RNA was not detected in any samples, while neutralizing (NT) antibodies were detected in serum samples of 53/20.8% of patients (95% CI = 16.0–26.3). In two patients, BHAV NT antibodies were detected in the CSF, indicating a recent infection. Both patients were inhabitants of rural areas in continental Croatia, and one reported a tick bite two weeks before symptoms onset. The seropositivity was high in all age groups (15.2–29.1%). The majority of seropositive patients (94.3%) resided at altitudes less than 200 m above sea level. The prevalence rates correlated positively with population density and negatively with certain climate parameters (temperature, number of hot/warm days). Conclusions: The presented results indicate that BHAV is distributed in Croatia. Further studies are needed to determine the clinical significance of this neglected arbovirus.

Limited scientific evidence shows that alpha lipoic acid (ALA) can induce regression rates of low-grade squamous intraepithelial lesions (LSILs), but the mechanisms of these effects have not been elucidated. To gain a broader insight into its therapeutic potential and mechanisms of action, the effects of 3 months of supplementation with 600 mg of ALA on antioxidant and lipid status parameters in 100 patients with LSILs were investigated in a randomized, placebo-controlled study. The obtained results are discussed in terms of patients’ initial metabolic status and diet quality (particularly nutritional intake of antioxidants). The obtained results showed that oxidative status biomarkers were not significantly affected by ALA supplementation. However, serum superoxide dismutase (SOD) activity was positively affected in the subgroup of patients with higher dietary antioxidant intake. Surprisingly, ALA supplementation resulted in a small but statistically significant increase in serum low density lipoprotein (LDL), and the observed effect was significantly affected by the initial lipid status of the participants. Larger studies are necessary to gain additional insights on the clinical significance of ALA as an antioxidant and hypolipemic agent and to optimize its potential application in LSIL treatment.

As for many solid cancers, laryngeal cancer is treated surgically, and adequate resection margins are critical for survival. Raman spectroscopy has the capacity to accurately differentiate between cancer and non-cancerous tissue based on their molecular composition, which has been proven in previous work. The aim of this study is to investigate whether Raman spectroscopy can be used to discriminate laryngeal cancer from surrounding non-cancerous tissue. Patients surgically treated for laryngeal cancer were included. Raman mapping experiments were performed ex vivo on resection specimens and correlated to histopathology. Water concentration analysis and CH-stretching region analysis were performed in the high wavenumber range of 2500–4000 cm^−1. Thirty-four mapping experiments on 22 resection specimens were used for analysis. Both laryngeal cancer and all non-cancerous tissue structures showed high water concentrations of around 75%. Discriminative information was only found to be present in the CH-stretching region of the Raman spectra of the larynx (discriminative power of 0.87). High wavenumber region Raman spectroscopy can discriminate laryngeal cancer from non-cancerous tissue structures. Contrary to the findings for oral cavity cancer, water concentration is not a discriminating factor for laryngeal cancer.

Introduction: Breast cancer (BC) is the most common malignancy in the female population globally. Obesity is associated with an increased risk of postmenopausal BC, BC recurrence, and mortality. Fat mass and obesity-associated (FTO) gene polymorphisms have attracted the most attention due to several single-nucleotide polymorphisms (SNPs) that may have an impact on obesity and different types of cancer. The primary goal of our work was to assess the association of the SNP rs17817449 FTO, physical status/metabolic changes, and dietary habits with the occurrence of BC. Methods: We conducted research as a population-genetic study including 93 women with a diagnosis of BC during their lifetime. Genomic DNA was extracted from the swabs of the buccal mucosa. Genotyping was achieved by polymerase chain reaction-restriction fragment length polymorphism. The IBM SPSS Statistics program v. 23.0 was used for statistical analysis. All values of p < 0.05 were considered statistically significant. Results: The risk genotype of the FTO gene (rs17817449) GG was detected in 16 subjects (17.2%), the heterozygous TG in 46 subjects (49.5%), while the normal genotype TT was recorded in 29 subjects (31.2%). We found no statistically significant difference in the body mass index values of the three genotype groups, p = 0.72, χ2 = 2.1 and no significant relationship between the allelic or genotypic frequencies of the rs17817449 FTO gene polymorphism and other variables examined in our study. Analysis of the distribution of hereditary diseases in the family according to the molecular subtype of BC showed statistically significant p-values, p = 0.02. Conclusion: While previous research has suggested a potential link between FTO gene polymorphism, obesity, and BC, our study did not find a statistically significant association between the aforementioned variables. Future studies with a larger number of subjects in different populations should confirm the role of the FTO genotype in the risk of BC.

In the context of sustainable buildings, an ecological study of building and insulating materials is critical since it may assist affirm or shift the path of new technology development. Utilising sustainable material is a part of the sustainable improvement. For this reason, material fabrication is the primary process for the energy usage and release of intense environmental gaseous. The fabrication of the insulation and building materials, as in every fabrication process, comprises an energy consumption of crude materials in addition to the pollutants’ release. In buildings, insulation is a relevant technological resolution for cutting energy usage. This study aims to assess the primary energy consumption and the environmental effects of the fabrication of building and thermal isolation materials by using a new hybrid MCDM model. The proposed new hybrid MCDM model includes Fuzzy FUCOM, CCSD and CRADIS methods. While the subjective weights of the criteria were determined with the fuzzy FUCOM method, the objective weights of the criteria were determined with the CCSD method. Construction materials were listed with the CRADIS method. According to the fuzzy FUCOM method, the most important criterion was determined as the CR3 criterion, while the most important criterion according to the CCSD method was determined as the CR1 criterion. According to the combined weights, the most important criterion was determined as the CR3 criterion. According to the CRADIS method, the material with the best performance was determined as Cement Plaster. The methodology used in this study is a novel approach therefore it has not been used in any study before. In addition, since the CRADIS method is a newly developed MCDM method, the number of articles related to this method is low. Therefore, this research gap will be filled with this study.

This paper provides an insight into measuring financial inclusion through a multidimensional index of financial inclusion in Southeast European countries (SEE). We used a two-stage principal component analysis to extract dimensions of financial inclusion. Data were obtained from two sources, the World Bank Global Findex Survey (WB-GFS) data base and the International Monetary Fund Financial Access Survey data (IMF-FAS), for twelve SEE countries for the years 2011, 2014, 2017, and 2021. The research confirms that financial inclusion can be measured using two dimensions in terms of access as one factor and usage and availability as the second factor. Practical implications of this research are in ensuring an adequate measure of the level of financial inclusion for SEE countries that can be used for further research related to understanding the underlying factors contributing to financial inclusion, barriers to financial inclusion as well as the impact of financial inclusion on economic growth and poverty alleviation.

Background: Chest pain represents a prevalent complaint in emergency departments (EDs), where the precise differentiation between acute coronary syndrome and alternative conditions assumes paramount significance. This pilot study aimed to assess the HEART score’s implementation in West Balkan EDs. Methods: A retrospective analysis was performed on a prospective cohort comprising patients presenting with chest pain admitted to EDs in Sarajevo, Zenica, and Belgrade between July and December 2022. Results: A total of 303 patients were included, with 128 classified as low-risk based on the HEART score and 175 classified as moderate-to-high-risk. The low-risk patients exhibited younger age and a lower prevalence of cardiovascular risk factors. Laboratory and anamnestic findings revealed higher levels of C-reactive protein, ALT, and creatinine, higher rates of moderately to highly suspicious chest pain history, a greater number of cardiovascular risk factors, and elevated troponin levels in moderate-to-high-risk patients. Comparatively, among patients with a low HEART score, 2.3% experienced MACE, whereas those with a moderate-to high-risk HEART score had a MACE rate of 10.2%. A moderate-to-high-risk HEART score demonstrated a sensitivity of 91.2% (95%CI 90.2–93.4%) and specificity of 46.5% (95%CI 39.9–48.3%) for predicting MACE. Conclusion: This pilot study offers preliminary insights into the integration of the HEART score within the emergency departments of the West Balkan region.

Homocysteine is known to be associated with adverse vascular and metabolic effects, as well as pregnancy complications. Its serum levels are influenced by the function of the enzyme methylenetetrahydrofolate reductase (MTHFR) and the dietary intake of folic acid, vitamin B12, and methionine. In this cross-sectional study, we investigated the association of genetic polymorphisms of the MTHFR gene with vitamin status in pregnant women during mandatory folic acid supplementation. The study included 102 pregnant women between 24 and 28 weeks of gestation who were attending regular outpatient examinations at the maternity clinic. Homocysteine, folic acid, vitamin B12 levels, and MTHFR gene polymorphisms (C677T and A1298C) were analyzed. Significant associations were found between vitamin B12 and folic acid levels with homocysteine (P< 0.001), with lower serum levels of these vitamins being associated with higher homocysteine levels. Surprisingly, there was no significant association between MTHFR genetic polymorphisms and serum homocysteine levels, likely attributed to the supplementation of folic acid and vitamin B12 in vitamin supplements for pregnant women, which counteracts the effect of the mutation. Remarkably, a high prevalence of MTHFR gene mutations was found, with the C677T polymorphism present in 56.9% and the A1298C polymorphism in 87.2% of pregnant women. These findings emphasize the importance of adequate folic acid and vitamin B12 intake during pregnancy to regulate homocysteine levels. Although the MTHFR gene mutations were highly prevalent, their influence on homocysteine levels in this population appears to be mitigated by vitamin supplementation. Further research is warranted to explore the impact of these mutations on other aspects of pregnancy outcomes. The trial is registered at Clinicaltrail.gov (NCT04952324).

We present eight cases of the homozygous MCPggaac haplotype, which is considered to increase the likelihood and severity of atypical hemolytic uremic syndrome (aHUS), especially in combination with additional risk aHUS mutations. Complement blockade (CBT) was applied at a median age of 92 months (IQR 36–252 months). The median number of relapses before CBT initiation (Eculizumab) was two. Relapses occurred within an average of 22.16 months (median 17.5, minimum 8 months, and maximum 48 months) from the first subsequent onset of the disease (6/8 patients). All cases were treated with PI/PEX, and rarely with renal replacement therapy (RRT). When complement blockade was applied, children had no further disease relapses. Children with MCPggaac haplotype with/without additional gene mutations can achieve remission through renal replacement therapy without an immediate need for complement blockade. If relapse of aHUS occurs soon after disease onset or relapses are repeated frequently, a permanent complement blockade is required. However, the duration of such a blockade remains uncertain. If complement inhibition is not applied within 4–5 relapses, proteinuria and chronic renal failure will eventually occur.