Aim To determine the relationship between coagulation disorders and septic condition in COVID-19 critically ill patients. Methods Data from 99 patients who presented with COVID-19 acute hypoxemic respiratory failure (CAHRF) were divided into two groups: Group 1- patients who developed sepsis, and Group 2 - patients who developed septic shock. Age, sex, comorbidities, quick Sequential Organ Failure Assessment (qSOFA) score, vasopressor and inotrope requirement, laboratory findings (platelets, neutrophils, lymphocytes, procalcitonin - PCT, C-reactive protein, fibrinogen, D-dimer, sepsis-induced coagulopathy - SIC, and disseminated intravascular coagulation - DIC score) were recorded on the day of admission and on the day of starting invasive mechanical ventilation. The primary outcome was to establish COVID-19 associated coagulopathy with sepsis and septic shock; the secondary outcome measure was incidence of coagulopathy in septic COVID-19 critically ill patients. Results The most common coagulation abnormality was international normalized ratio (INR) (p=0.019) for Group 2, followed by the values of inflammatory parameters PCT (p=0.002) and lymphocytes (p=0.011) also for Group 2. The statistical significance of SIC score was observed for both groups (p=0.007) and p=0.012, respectively. Norepinephrine (p=0.000) and dobutamine (p=0.000) for Group 2, qSOFA for both groups (p = 0.000) were statistically significant. Conclusion The observed coagulation abnormalities met the criteria for a SIC diagnosis, therefore, the management of coagulation disorders at this stage of the disease should follow the management of a septic condition.

The constant worsening of antimicrobial resistance (AMR) imposes the need for an urgent response. Use of antibiotics (AB), both due to irrational prescribing by doctors and irrational use by patients, is recognized as one of the leading causes of this problem. This study aimed to identify knowledge, attitudes, and practices about AB use and AMR within the general population, stratified by age, gender, and urban/rural areas during the COVID-19 pandemic. This questionnaire-based cross-sectional study was conducted in April 2022 among patients who visited three health centers in the eastern region of Bosnia and Herzegovina. A high frequency of AB use was observed during the COVID-19 pandemic (64.2% of respondents were treated with AB). Age and place of residence have not been shown to be factors associated with AB use practices that pose a risk for AMR. However, female gender (β = 0.063; p = 0.041), better knowledge (β = 0.226; p < 0.001), and positive attitudes (β = 0.170; p < 0.001) about use of AB and towards to AMR proved to be factors associated with better practice by respondents. Women, younger respondents, and respondents from urban areas showed better knowledge, attitudes, and behavior about the use of AB and AMR during the COVID-19 pandemic.

Entre os vários problemas ambientais da contemporaneidade, a falta do reconhecimento da importância da botânica no nosso cotidiano, a ausência de sensibilização e a interação com a natureza são assuntos que a sociedade deve discutir. O presente trabalho, a fim de buscar e implantar possibilidades dentro da Educação Ambiental (EA), traz a proposta de formatação de uma trilha interpretativa conduzida e/ou autoconduzida de uma forma didático-pedagógica no campus da Universidade Estadual de Santa Cruz (UESC). A metodologia propõe uma dupla análise ao utilizar os métodos de Indicadores de Atratividades de Pontos Interpretativos (IAPI) e o Valor Turístico (Vtur). Foram realizadas visitas ao Horto Florestal da UESC e, com o auxílio do GPS Garmin etrex 10x e do aplicativo de celular TCpGPS, propomos um novo trajeto da trilha de 1.047 metros, com design circular e 10 pontos interpretativos. Diante disso, é possível afirmar que as metodologias utilizadas na proposta atingiram seu escopo ao possibilitar o conhecimento da flora local, das relações ecológicas, da acessibilidade, bem como do desenvolvimento de atitudes e valores diante do meio ambiente, de forma prática e sistematizada.

A sociedade experimenta uma forma de economia calcada em tecnologias de vigilância, que influenciou na conflagração de dados em camadas incomensuráveis. Nesse contexto, aparelha-se um desafio para a pesquisa científica, que deve acontecer obedecendo os padrões nacionais de proteção de dados pessoais. Para tanto, o presente trabalho objetiva estabelecer os padrões da LGPD para pesquisa científica, o contexto histórico que fundamenta a importância da ética na pesquisa e os perigos de uma regulamentação rígida da pesquisa através da LGPD que pode ferir direitos fundamentais. O método utilizado é o hipotético-dedutivo, com utilização de recursos bibliográficos e documentais. Em conclusão, a LGPD revela uma nova realidade para a pesquisa científica, transformando o pesquisador ou órgão de pesquisa em agentes de tratamento, com devidas responsabilidades no tratamento de dados pessoais dos humanos envolvidos na pesquisa científica. 

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.

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.

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.