Abstract Work intensification is a psychosocial risk that has been increasing in recent decades and may have been accentuated after the COVID-19 pandemic. Its effects on health are negative, but they can be moderated by contextual and personal factors. The aim of this study was twofold: to analyze the effect of work intensification on workers’ stress, anxiety, and depression and to explore the role of workplace curiosity in these relationships. The study design was cross-sectional, and a total of 766 Spanish workers (58.9% female) with different occupations completed the survey. The results showed that work intensification was associated with the symptomatology of stress, anxiety, and depression, with a medium effect size. Women workers showed higher work intensification, but its association with mental health was equally strong for both genders. Workers with higher levels of the workplace curiosity dimension “stress tolerance” showed less impaired mental health in the presence of work intensification. However, workers with higher levels of the workplace curiosity dimension “deprivation sensitivity” showed more symptoms of stress, anxiety, and depression when faced with high work intensification. The results were discussed in terms of their contributions to the field of study of work intensification, the future research they could inspire, and the prevention and intervention measures they could motivate.

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.

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.

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.

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.

INTRODUCTION This systematic review aimed to examine a potential link between apical periodontitis (AP) and gastrointestinal diseases (GIDs). METHODS The protocol of the review has been registered in PROSPERO (CRD42022330771). The following engines were used with the aim of searching for relevant literature: PubMed, Web of Science, Scopus, Cochrane Central Register of Controlled Trials, and grey literature, from inception to May 2022. There were no language restrictions included. Study selection, data collection and synthesis have been performed by two independent reviewers. For the purpose of estimating the quality of studies, the Newcastle-Ottawa Scale (NOS) was used. RESULTS Four matched case control studies, as well as a single longitudinal cohort study were included in the final review. These were published between 2017 and 2012,and comprised 537 participants whose age range was 18 to 87 years. It was not possible to perform a meta-analysis due to different study designs and evaluated outcomes of included studies. Except for one study that was categorized as 'Good', overall, for four out of five studies the quality was assessed as 'Fair'. CONCLUSIONS This review highlighted sparse knowledge present in the literature concerned with the association between AP and GIDs. Available evidence reveals a potential link between impaired endodontic status, assessed by the number of root filled teeth with periapical radiolucency, and GIDs. More research is needed to ascertain this association.

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.

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.

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.

Aim To determine risk factors associated with the development and severity of secondary hyperparathyroidism in dialysis patients. Methods A cross-sectional study at the Clinical Centre of the University of Tuzla (March 2022) included 104 adult patients (males 51.9%, females 48.1%) with chronic kidney diseases under dialysis treatment. Based on parathyroid hormone (PTH) values, patients were divided into two groups: study group (45/104, PTH >792pg/mL) and control group (59/104, PTH 176-792 pg/ mL). The analysis aimed to resolve whether there was a connection between the duration of dialysis, the type of therapy treatment administered, the underlying kidney disease, and the presence of comorbidities with the values of PTH, and a wide spectrum of monitored laboratory parameters. Results The most common causes of chronic renal failure were undefined kidney diseases (32.7%), followed by diabetic nephropathy (18.3%) and chronic glomerulonephritis (16.3%). In the examined biochemical parameters, a significant difference was found in mean values of alkaline phosphatase (p<0.001). The correlation was proved between the duration of dialysis (p=0.028), the values of phosphorus (p=0.031), and alkaline phosphatase (p<0.001) with absolute values of PTH. The most common present comorbidity was hypertension (78.8%), followed by cardiovascular diseases (40.4%) and diabetes (22.1%). Conclusion A number of factors contribute to the development and severity of SHPT. Modulation of therapy and better control of risk parameters can prolong and reduce the frequency of SHPT in dialysis patients, as well as the occurrence of comorbidities.

Aims: The aim of this study was to conduct antimicrobial analysis on novel Schiff base-derived cobalt(II) complexes (Co(L1) 2 and Co(L2) 2 )

STUDY OBJECTIVES Little is known about the effectiveness of bridge clinics as transitional care programs for people with opioid use disorder in emergency departments (EDs). We assessed the effect of bridge clinic referral on health services use among patients with opioid use disorder identified in the ED. METHODS We used data for individuals aged 18 years and over with active opioid use disorder and no history of medication for opioid use disorder who were administered medication for opioid use disorder while in the ED between January 2013 and August 2022. Bridge clinic referrals started in January 2021. Eligible patients after this date comprised the intervention group. The usual care group included eligible patients before bridge clinic implementation, who were a 1:1 propensity score matched to intervention patients. We estimated risk differences and 95% confidence limits for linkage to long-term care, ED use, and inpatient admission within 120 days of the index ED visit. RESULTS Our study population comprised 928 observations after matching. Patients referred to the bridge clinic had a higher risk of linkage to long-term care (risk differences=25%; 95% confidence limits: 20%, 30%), higher risk of ED use (risk differences=7.5%, 95% confidence limits: 1.6%, 13%), and lower risk of inpatient admission (risk differences= -1.9%, 95% confidence limits: -5.9%, 2.1%). Inpatient admission increased among patients with serious mental illness but decreased among patients without serious mental illness. CONCLUSION Our overall results suggest that bridge clinic referral increases linkage to long-term care. Nevertheless, qualitatively different effects on inpatient admission between patients with and without serious mental illness warrant consideration of unmet needs among patients with serious mental illness.

Metastatic colorectal cancer (CRC) is a common cause of cancer-related mortality, of which peritoneal metastases (PMs) have the worse outcome. Metastasis-specific markers may help predict the spread of tumor cells and select patients for preventive strategies. This exploratory pilot study aimed to gain more insight into genetic alterations in primary CRC tumors, which might be a predictive factor for the development of PM. Forty patients with T3 stage CRC were retrospectively divided in three groups: without metachronous metastases during 5-year follow-up (M0, n = 20), with metachronous liver metastases (LM, n = 10) and with metachronous PM (PM, n = 10). Patients with synchronous metastases were excluded. Primary formalin-fixed paraffin-embedded tumor samples were analyzed via comprehensive genome sequencing (TSO500 analysis) to identify DNA alterations and RNA fusion transcripts in 523 genes and 55 genes, respectively. Thirty-eight samples were included for final analysis. Four M0 tumors and one PM tumor were microsatellite instable. BRAF mutations were uniquely identified in three microsatellite-stable (MSS) PM tumors (37.5%, p = 0.010). RNA analysis showed an additional FAM198A-RAF1 fusion in one PM sample. BRAF p.V600E mutations were only present in PM patients with MSS tumors. Greater attention should be paid to BRAF-mutated tumors in relation to the development of metachronous PM.