Mitochondrial DNA (mtDNA) has been used for decades as a predominant tool in population genetics and as a valuable addition to forensic genetic research, owing to its unique maternal inheritance pattern that enables the tracing of individuals along the maternal lineage across numerous generations. The dynamic interplay between evolutionary forces, primarily genetic drift, bottlenecks, and the founder effect, can exert significant influence on genetic profiles. Consequently, the Adriatic islands have accumulated a subset of lineages that exhibits remarkable absence or rarity within other European populations. This distinctive genetic composition underscores the islands’ potential as a significant resource in phylogenetic research, with implications reaching beyond regional boundaries to contribute to a global understanding. In the initial attempt to expand the mitochondrial forensic database of the Croatian population with haplotypes from small isolated communities, we sequenced mitogenomes of rare haplogroups from different Croatian island and mainland populations using next-generation sequencing (NGS). In the next step and based on the obtained results, we refined the global phylogeny of haplogroup N1a, HV2, and X by analyzing rare haplotypes, which are absent from the current phylogenetic tree. The trees were based on 16 novel and 52 previously published samples, revealing completely novel branches in the X and HV2 haplogroups and a new European cluster in the ancestral N1a variant, previously believed to be an exclusively African–Asian haplogroup. The research emphasizes the importance of investigating geographically isolated populations and their unique characteristics within a global context.

BACKGROUND The Intensification of Job Demands Scale (IDS) is a multidimensional instrument designed to capture the phenomenon of work intensification that characterizes modern Western societies. However, in Spain the instrument has not been validated to assess this phenomenon. The aim of this study was to examine the psychometric properties of the IDS adaptation with a heterogeneous sample of Spanish workers. METHOD The sample consisted of 722 Spanish workers (57.8% female, 42.2% male) who completed a survey between January and April 2022. RESULTS A five-factor correlated model, as in the original IDS, had an optimal fit with 15 items, and displayed invariance across gender, level of education, and organizational tenure. Reliability coefficients were all satisfactory, and scale adaptation showed evidence of convergent, discriminant, and incremental validity. CONCLUSIONS The Spanish adaptation of the IDS is a valid, reliable measure for analyzing the phenomenon of work intensification and intensified job demands in Spain.

Aim To assess morphological characteristics of carotid blood vessels in uremic patients before to the initiation of the dialysis treatment, and corelate data with various dialysis therapy modules. Methods The study included 30 patients with end-stage renal disease (ERDS) prior to commencing dialysis, 30 patients treated with haemodialysis and 30 patients treated with continuous ambulatory peritoneal dialysis. The control group consisted of 15 subjects with normal kidney function (eGFR>60ml/min). Carotid intima-media thickness (CIMT), as well as lipid status values (cholesterol, triglycerides, low-density lipoprotein (LDL), high-density lipoprotein (HDL), apolipoprotein A, apolipoprotein B) were evaluated. Results The significant difference in CIMT was detected between the control and haemodialysis groups (p<0.001), and between the control and the peritoneal dialysis group (p=0.004). In patients in the predialysis group, CIMT was influenced by cholesterol (p=0.013), HDL (p=0.044), LDL (p=0.001) and ApoB (p=0.042) values. A significant difference in CIMT was proved between the haemodialysis and predialysis group of patients (p<0.001). The only variable from the patient's lipometabolic profile significantly associated with the change in IMT in uremic patients was HDL. A significant difference was found in the average value for systolic blood pressure (p<0.001) and diastolic blood pressure (p=0.018) in patients before starting the dialysis treatment compared to patients treated with other dialysis methods. Conclusion Patients on haemodialysis treatment had a significantly greater CIMT, which is in relation with a higher cardiovascular risk.

Background Patients with chronic lymphocytic leukemia (CLL) are vulnerable to coronavirus disease 2019 (COVID-19) and are at risk of inferior response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination, especially if treated with the first-generation Bruton’s tyrosine kinase inhibitor (BTKi) ibrutinib. We aimed to evaluate the impact of the third-generation BTKi, zanubrutinib, on systemic and mucosal response to SARS-CoV-2 vaccination. Methods Nine patients with CLL with ongoing zanubrutinib therapy were included and donated blood and saliva during SARS-CoV-2 vaccination, before vaccine doses 3 and 5 and 2 - 3 weeks after doses 3, 4, and 5. Ibrutinib-treated control patients (n = 7) and healthy aged-matched controls (n = 7) gave blood 2 - 3 weeks after vaccine dose 5. We quantified reactivity and neutralization capacity of SARS-CoV-2-specific IgG and IgA antibodies (Abs) in both serum and saliva, and reactivity of T cells activated with viral peptides. Results Both zanubrutinib- and ibrutinib-treated patients had significantly, up to 1,000-fold, lower total spike-specific Ab levels after dose 5 compared to healthy controls (P < 0.01). Spike-IgG levels in serum from zanubrutinib-treated patients correlated well to neutralization capacity (r = 0.68; P < 0.0001) and were thus functional. Mucosal immunity (specific IgA in serum and saliva) was practically absent in zanubrutinib-treated patients even after five vaccine doses, whereas healthy controls had significantly higher levels (tested in serum after vaccine dose 5) (P < 0.05). In contrast, T-cell reactivity against SARS-CoV-2 peptides was equally high in zanubrutinib- and ibrutinib-treated patients as in healthy control donors. Conclusions In our small cohort of zanubrutinib-treated CLL patients, we conclude that up to five doses of SARS-CoV-2 vaccination induced no detectable IgA mucosal immunity, which likely will impair the primary barrier defence against the infection. Systemic IgG responses were also impaired, whereas T-cell responses were normal. Further and larger studies are needed to evaluate the impact of these findings on disease protection.

Current data suggest that aristolochic acid (AA) exposure is a putative cause of Balkan endemic nephropathy (BEN), a chronic kidney disease strongly associated with upper tract urothelial carcinoma. The cellular metabolism of AA is associated with the production of reactive oxygen species, resulting in oxidative distress. Purpose: Therefore, the aim of this study was to analyze individual, combined and cumulative effect of antioxidant gene polymorphisms (Nrf2 rs6721961, KEAP1 rs1048290, GSTP1AB rs1695, GSTP1CD rs1138272, GPX3 rs8177412 and MDR1 rs1045642), as well as GSTP1ABCD haplotypes with the risk for BEN development and associated urothelial cell carcinoma in 209 BEN patients and 140 controls from endemic areas. Experimental method: Genotyping was performed using polymerase chain reaction (PCR) and PCR with confronting two-pair primers (PCR-CTTP) methods. Results: We found that female patients carrying both variant GPX3 rs8177412 and MDR1 rs1045642 genotypes in combination exhibited significant risk towards BEN (OR 1 = 3.34, 95% CI = 1.16–9.60, p = 0.025; OR 2 = 3.79, 95% CI = 1.27–11.24, p = 0.016). Moreover, significant association was determined between GPX3rs8174412 polymorphism and risk for urothelial carcinoma. Carriers of variant GPX3*TC + CC genotype were at eight-fold increased risk of BEN-associated urothelial tumors development. There was no individual or combined impact on BEN development and BEN-associated tumors among all examined polymorphisms. The haplotype consisting of variant alleles for both polymorphisms G and T was associated with 1.6-fold increased risk although statistically insignificant (OR = 1.64; 95% CI = 0.75–3.58; p = 0.21). Conclusions: Regarding GPX3 rs8177412 polymorphism, the gene variant that confers lower expression is associated with significant increase in upper urothelial carcinoma risk. Therefore, BEN patients carrying variant GPX3 genotype should be more frequently monitored for possible upper tract urothelial carcinoma development.

Simple Summary This study aimed to investigate if the coexpression of ABC transporters and survivin is associated with R-CHOP treatment response. Bcl-2 was in strong positive correlation with clinical parameters and all biomarkers except P-gp/ABCB1. The overexpression of MRP1/ABCC1, survivin, and BCRP/ABCC2 presented as high immunoreactive scores (IRSs) was detected in Refractory and Relapsed groups, respectively, whereas the IRS of P-gp/ABCB1 was low. Significant correlations were found among either MRP1/ABCC1 and survivin or BCRP/ABCC2 expression in the Refractory and Relapsed groups, respectively. In multiple linear regression analysis, ECOG status along with MRP1/ABCC1 or survivin, and BRCP/ABCG2 was significantly associated with the prediction of the R-CHOP treatment response. DLBCL might have increased levels of certain molecules such as MRP1/ABCC1, survivin, and BCRP/ABCC2 that can predict resistance to R-CHOP. Abstract Background: Approximately 40% of patients with diffuse large B-cell lymphoma (DLBCL) experience treatment resistance to the first-line R-CHOP regimen. ATP binding cassette (ABC) transporters and survivin might play a role in multidrug resistance (MDR) in various tumors. The aim was to investigate if the coexpression of ABC transporters and survivin was associated with R-CHOP treatment response. Methods: The expression of Bcl-2, survivin, P-glycoprotein/ABCB1, MRP1/ABCC1, and BCRP/ABCC2 was analyzed using immunohistochemistry in tumor specimens obtained from patients with DLBCL, and classified according to the treatment response as Remission, Relapsed, and (primary) Refractory groups. All patients received R-CHOP or equivalent treatment. Results: Bcl-2 was in strong positive correlation with clinical parameters and all biomarkers except P-gp/ABCB1. The overexpression of MRP1/ABCC1, survivin, and BCRP/ABCC2 presented as high immunoreactive scores (IRSs) was detected in the Refractory and Relapsed groups (p < 0.05 vs. Remission), respectively, whereas the IRS of P-gp/ABCB1 was low. Significant correlations were found among either MRP1/ABCC1 and survivin or BCRP/ABCC2 in the Refractory and Relapsed groups, respectively. In multiple linear regression analysis, ECOG status along with MRP1/ABCC1 or survivin and BRCP/ABCG2 was significantly associated with the prediction of the R-CHOP treatment response. Conclusions: DLBCL might harbor certain molecular signatures such as MRP1/ABCC1, survivin, and BCRP/ABCC2 overexpression that can predict resistance to R-CHOP.

Aim To investigate the frequency of consumption of sweet and salty snacks among children aged 2-18 years in relation to their mothers' education level. Methods A descriptive epidemiological study was conducted in five dental practices at the School of Medicine of the University of Mostar from May to October 2022. The data were collected from medical records. Results: Out of a total of 477 children, 172 (36.1%) had mothers with a high school education, while 305 (63.9%) had mothers with a university degree. In the group of preschool children (aged 2-6 years), there were 42 mothers with high school education and 105 with university degree. In the group of school children (age 7-18 years) there were 130 mothers with high school education and 200 with university degree. The difference in the consumption of sweetened beverages among children of mothers with high school and university was not statistically significant. Similar results were found for the consumption of salty snacks, lollipops, caramels and candies. The frequency of the consumption of biscuits, chocolate and cakes (several times a day) was statistically significantly higher among the children of mothers with high school education (p=0.04), especially among school children. Eating habits of children, regardless of the level of education of their mothers, differed significantly only in the consumption of lollipops, caramels, and candies (p=0.03), which were consumed once a day by 79 (63.7%) schoolchildren and 45 (36.3%) of pre-schoolers. Conclusion A higher level of education among mothers does not necessarily equate to proper nutritional knowledge.

- The influence of multi-hole orifice flow meter geometry parameters on the parameters of Newtonian fluid through multi-hole orifice meters was investigated using computational fluid dynamics as well as the effect of contamination in front of the MHO flow meter. The air flow was steady, three-dimensional, and turbulent. Analysed Newtonian fluid was air and physical properties that were considered were density and dynamic viscosity. The numerical method was finite volume method, and standard k-ε turbulence model was used for turbulence modelling. Multi-hole orifice meter with thre e different β parameters 0.5 5, 0.6 and 0.7, was observed and Reynold’s number was 10 5 . The pressure drop and discharge coefficient were analysed. Numerical simulations were performed using commercial software the STAR-CCM+ 2019.2. It was found that increase in 𝛽𝛽 parameter results with the decrease in pressure drop and increase in discharge coefficient. Also, it was found that that the influence of 𝛽𝛽 parameter is much higher when analyzing pressure drop rather than discharge coefficient values. Numerical simulations were also performed to investigate the effect of contaminations in front of the MHO plate with 𝛽𝛽 = 0.5, on the discharge coefficients. It was found that as the contamination angle is increased the discharge coefficient tends to increase.

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Partial or complete dentures are constructed from thermoplastic resins that are thermally processed and molded. This review examines the presently available evidence for the cytotoxicity of thermoplasticized denture base resins on human gingival epithelial cells, adipose cells, and fibroblasts; human amnion fibroblasts; and mouse fibroblasts. Electronic searches were performed on PubMed, Scopus, Web of Science, and Google Scholar databases to identify relevant articles to be included in the review until September 2022. Clinical, in vivo, and in vitro studies in English language were searched for. The quality of the studies was assessed using the Toxicological data Reliability Assessment tool (ToxRTool) developed by the European Commission’s Joint Research Centre. GRADE assessment was used to evaluate the certainty of evidence. Seven in vitro studies were included in the review. The overall risk of bias was determined to be high, with the majority of studies assessed found to be reliable with restrictions or not reliable. Only two studies were considered reliable without restrictions based on ToxRTool assessment. The effect of thermoplastic denture base resins on viability and cell adherence of human gingival or amnion fibroblasts and mouse fibroblasts (L929s) is not significant. Conditioned media from unpolished specimens of resins were significantly more toxic to cultured cells than those from polished specimens. This may be of concern in cases of poor post-processing of dentures. Based on the limited evidence available, there is low-certainty evidence that thermoplastic denture base resins appear to be biocompatible and show insignificant cytotoxicity. Further well-designed trials adhering to standard reporting guidelines and using objective measures are necessary before outlining universal guidelines for best practice. Long-term in vivo and clinical assessment is necessary to corroborate laboratory findings with clinical outcomes. Denture base resins are in constant contact with oral tissues, and cytotoxic components released by the resins may irritate or inflame the tissues or provoke an allergic response.