Is there a relationship between attitudes of general practitioners/family doctors and attitudes of their patients regarding industry-sponsored clinical investigations? A cross-sectional survey in a convenience sample of doctors and patients across nine European countries.

AIM: To assess the relationship between the attitudes of general practitioners/family medicine doctors (GP/FD) and of their patients toward industry-sponsored clinical research. METHODS: A cross-sectional survey included volunteer GPs/FDs who then enrolled and interviewed their patients. Data were analyzed in hierarchical models (patients nested in GPs/FDs, nested in countries/regions). RESULTS: A total of 201 GPs/FDs from nine European countries responded to the invitation and enrolled 995 of their patients. We observed mild associations between some of the GPs/FDs' attitudes (general opinion on sponsored clinical studies, appreciation of the general values of such studies, views about the importance of participant protection/privacy) and some of the patients' attitudes (appreciation of the general values and of risks associated with sponsored clinical studies, importance assigned to potential personal benefits from participation). We observed no association between GPs/FDs' attitudes and patients' willingness to participate in such studies. However, willingness to participate increased with higher patients' appreciation of the general values of sponsored studies, decreased with higher patients' appreciation of associated risks, and showed a quadratic trend across the levels of importance assigned by patients to potential personal benefits (willingness was higher when the assigned importance was very low or very high). More importance to GP/FD's advice in this respect was assigned by patients who assigned more importance to potential personal benefits, who were better educated, and who resided in rural/suburban dwellings. CONCLUSIONS: In the present convenience sample, lay-person attitudes about and willingness to participate in industry-sponsored clinical studies were associated with the attitudes of their GPs/FDs.

Clinical and epidemiological risk factors associated with hospitalization and mortality rate of COVID-19 patients in Banja Luka County: A retrospective observational cohort study on 40,000 patients.

Context: Since beginning of the coronavirus disease (COVID-19) it became clear that severe forms of this infection have primarily affected patients with chronic conditions. Aims: The aim of the study was to explore clinical and epidemiological characteristics associated with COVID 19 outcomes. Settings and Design: The retrospective observational study included 40,692 citizens of Banja Luka County, Bosnia and Herzegovina, who were confirmed as reverse transcriptase polymerase chain reaction (RT-PCR) positive on COVID-19 at a primary healthcare centre from March 2020 to September 2022. Methods and Materials: Epidemiological data were obtained from Web-Medic medical records of patients. The COVID-19 data were obtained from COVID-19 data sheets comprised of patients' RT-PCR testing forms, surveillance forms for severe acute respiratory syndrome coronavirus-2 status, and a map of their positive and isolated contacts. Statistical Analysis Used: Differences regarding the distributions of patients between groups were analysed using the Pearson chi-square test and Mantel-Haenszel chi-square test for trends, while differences in mean values were compared using an independent sample t-test. Results: The average age of hospitalised patients was significantly higher compared to the age of non-hospitalised patients (P < 0.001). The average age of patients with lethal outcomes was nearly twice as high in comparison to patients with non-lethal outcomes (P < 0.001). Male patients had a higher hospitalization and mortality rate (P < 0.001). The highest hospitalization rate was in patients with chronic renal failure (CRF), diabetes and cardiovascular diseases (CVDs), while the death rate was the highest among patients with CRF and hearth comorbidities. Patients with fatigue and appetite loss had a higher percentage of lethal outcomes. Vaccinated patients had a significantly lower rate of lethal outcome. Conclusions: Clinical symptoms, signs and outcomes, are posing as predictive parameters for further management of COVID-19. Vaccination has an important role in the clinical outcomes of COVID-19.

Molnupiravir's real-world effectiveness in COVID-19 outpatients at high risk of severe disease: a single-center study.

INTRODUCTION: The coronavirus disease 2019 (COVID-19) pandemic started in March 2020. Since then, there has been an urgent need for effective therapeutic methods to manage the disease. We aimed to assess the effectiveness of molnupiravir in reducing the need for hospitalization in at-risk, non-hospitalized COVID-19 patients. METHODOLOGY: This was a single-center, non-randomized, observational retrospective study of non-hospitalized patients with confirmed COVID-19, treated at the Clinic for Infectious and Tropical Diseases, University Clinical Center in Belgrade, Serbia. RESULTS: The study was conducted between 15 December 2021 and 15 February 2022 and included 320 patients. Of these, 165 (51.6%) received treatment with molnupiravir. The study and control groups were similar in gender and age distribution. The study group had a higher proportion of vaccination (75.2% vs. 51%, p < 0.001). There was no statistically significant difference in presence of comorbidity within the groups. Majority of the patients who received molnupiravir did not require hospitalization; and this was statistically significant in comparison to control group (92.7 vs. 24.5%, p < 0.001). Oxygen supplementation was less frequently required in the study group compared to the control group (0.6% vs. 31%, p < 0.001). During the follow-up period of 12.12 ± 3.5 days, significantly less patients from the study group were admitted to the intensive care unit (p < 0.001). Molnupiravir significantly reduced the risk of hospitalization by 97.9% (HR 0.021; 95% CI 0.005-0.089; p < 0.001). CONCLUSIONS: Molnupiravir is an effective therapy in preventing the development of severe forms of COVID-19 and hospitalization.

Metadherin-driven promotion of cancer stem cell phenotypes and its effect on immunity in hepatocellular carcinoma.

In this editorial we provide commentary on the article published by Wang et al, featured in the recent issue of the World Journal of Gastroenterology in 2024. We focus on the metadherin (MTDH), also known as astrocyte elevated gene-1 or lysine rich CEACAM1, and its effects on cancer stem cells (CSCs) and immunity in hepatocellular carcinoma (HCC). HCC is the most common primary liver cancer and one of the leading causes of cancer-related deaths worldwide. Most HCC cases develop in the context of liver cirrhosis. Among the pivotal mechanisms of carcinogenesis are gene mutations, dysregulation of diverse signaling pathways, epigenetic alterations, hepatitis B virus-induced hepatocarcinogenesis, chronic inflammation, impact of tumor microenvironment, oxidative stress. Over the years, extensive research has been conducted on the MTDH role in various tumor pathologies, such as lung, breast, ovarian, gastric, hepatocellular, colorectal, renal carcinoma, neuroblastoma, melanoma, and leukemias. Specifically, its involvement in tumor development processes including transformation, apoptosis evasion, angiogenesis, invasion, and metastasis via multiple signaling pathways. It has been demonstrated that knockdown or knockout of MTDH disrupt tumor development and metastasis. In addition, numerous reports have been carried out regarding the MTDH influence on HCC, demonstrating its role as a predictor of poor prognosis, aggressive tumor phenotypes prone to metastasis and recurrence, and exhibiting significant potential for therapy resistance. Finally, more studies finely investigated the influence of MTDH on CSCs. The CSCs are a small subpopulation of tumor cells that sharing traits with normal stem cells like self-renewal and differentiation abilities, alongside a high plasticity that alters their phenotype. Beyond their presumed role in tumor initiation, they can drive also disease relapse, metastasis, and resistance to chemo and radiotherapy.

Neurological and neuromuscular manifestations in patients with West Nile neuroinvasive disease, Belgrade area, Serbia, season 2022.

INTRODUCTION: We aimed to describe neurological manifestations and functional outcome at discharge in patients with West Nile neuroinvasive disease. METHODS: This retrospective study enrolled inpatients treated in the University Clinic for Infectious and Tropical Diseases in Belgrade, Serbia, from 1 June until 31 October 2022. Functional outcome at discharge was assessed using modified Rankin scale. RESULTS: Among the 135 analyzed patients, encephalitis, meningitis and acute flaccid paralysis (AFP) were present in 114 (84.6%), 20 (14.8%), and 21 (15.6%), respectively. Quadriparesis/quadriplegia and monoparesis were the most frequent forms of AFP, present in 9 (6.7%) and 6 (4.4%) patients, respectively. Fourty-five (33.3%) patients had cerebellitis, 80 (59.3%) had rhombencephalitis, and 5 (3.7%) exhibited Parkinsonism. Ataxia and wide-based gait were present in 79 (58.5%) patients each. Fifty-one (37.8%) patients had tremor (41 (30.3%) had postural and/or kinetic tremor, 10 (7.4%) had resting tremor). Glasgow coma score (GCS) ≤ 8 and respiratory failure requiring mechanical ventilation developed in 39 (28.9%), and 33 (24.4%) patients, respectively. Quadriparesis was a risk factor for prolonged ventilator support (29.5 ± 16.8 vs. 12.4 ± 8.7 days, p = 0.001). At discharge, one patient with monoparesis recovered full muscle strength, whereas 8 patients with AFP were functionally dependent. Twenty-nine (21.5%) patients died. All of the succumbed had encephalitis, and 7 had quadriparesis. Ataxia, tremor and cognitive deficit persisted in 18 (16.9%), 15 (14.2%), and 22 (16.3%) patients at discharge, respectively. Age, malignancy, coronary disease, quadriparesis, mechanical ventilation, GCS ≤ 8 and healthcare-associated infections were risk factors for death (p = 0.001; p = 0.019; p = 0.004; p = 0.001; p < 0.001; p < 0.001, and p < 0.001, respectively).

HCV and HCC Tango-Deciphering the Intricate Dance of Disease: A Review Article.

Hepatitis C virus (HCV) is a major cause of hepatocellular carcinoma (HCC) accounting for around one-third of all HCC cases. Prolonged inflammation in chronic hepatitis C (CHC), maintained through a variety of pro- and anti-inflammatory mediators, is one of the aspects of carcinogenesis, followed by mitochondrial dysfunction and oxidative stress. Immune response dysfunction including the innate and adaptive immunity also plays a role in the development, as well as in the recurrence of HCC after treatment. Some of the tumor suppressor genes inhibited by the HCV proteins are p53, p73, and retinoblastoma 1. Mutations in the telomerase reverse transcriptase promoter and the oncogene catenin beta 1 are two more important carcinogenic signaling pathways in HCC associated with HCV. Furthermore, in HCV-related HCC, numerous tumor suppressor and seven oncogenic genes are dysregulated by epigenetic changes. Epigenetic regulation of gene expression is considered as a lasting "epigenetic memory", suggesting that HCV-induced changes persist and are associated with liver carcinogenesis even after cure. Epigenetic changes and immune response dysfunction are recognized targets for potential therapy of HCC.

Metabolic Associated Fatty Liver Disease (MAFLD) and COVID-19 Infection: An Independent Predictor of Poor Disease Outcome?

Background and Objectives: Early reports on COVID-19 infection suggested that the SARS-CoV-2 virus solely attacks respiratory tract cells. As the pandemic spread, it became clear that the infection is multiorganic. Metabolic associated fatty liver disease (MAFLD) is a chronic liver disease strongly associated with insulin resistance and diabetes. The aim of this study was to assess a possible interplay between MAFLD and COVID-19 infection and its implication in COVID-19 outcome. Materials and Methods: A retrospective observational study, including 130 COVID-19 positive patients was conducted. MAFLD diagnosis was made based on the International Consensus criteria. Patients were divided into two groups, group A (MAFLD) and group B (nonMAFLD). Anthropometric and laboratory analysis were obtained. COVID-19 severity was assessed using the NEWS2 score. Disease outcome was threefold and regarded as discharged, patients who required mechanical ventilation (MV), and deceased patients. Results: MAFLD prevalence was 42%, 67% of patients were discharged, and 19% needed MV. Mortality rate was 14%. MAFLD patients were significantly younger (p < 0.001), and had higher body mass index (p < 0.05), respiratory rate (p < 0.05) and systolic blood pressure (p < 0.05) than nonMAFLD patients. Regarding metabolic syndrome and inflammatory markers: group A had significantly higher glycemia at admission (p = 0.008), lower HDL-c (p < 0.01), higher triglycerides (p < 0.01), CRP (p < 0.001), IL-6 (p < 0.05) and ferritin (p < 0.05) than group B. MAFLD was associated with more prevalent type 2 diabetes (p = 0.035) and hypertension (p < 0.05). MAFLD patients had a more severe disease course (NEWS2 score, 6.5 ± 0.5 vs. 3 ± 1.0, p < 0.05). MAFLD presence was associated with lower patient discharge (p < 0.01) and increased need for MV (p = 0.024). Multiple regression analysis showed that BMI (p = 0.045), IL-6 (p = 0.03), and MAFLD (p < 0.05) are significant independent risk factors for a poor COVID-19 outcome. Conclusions: The prevalence of MAFLD is relatively high. MAFLD patients had a more severe COVID-19 clinical course and worse disease outcome. Our results imply that early patient stratification and risk assessment are mandatory in order to avoid poor outcomes.

Influence of chronic liver diseases on the course and outcome of COVID-19.

INTRODUCTION: Coronavirus disease of 2019 (COVID-19) is a global health problem. The impact of chronic liver diseases on the course and outcome of COVID-19 is still the subject of research. The aim of this study was to show the characteristics of COVID-19 patients with chronic liver diseases, and to establish the risk factors for unfavourable outcome. METHODS: A retrospective observational study was conducted at the Infectious Disease Clinic in Belgrade, Serbia, and included 80 patients with chronic liver diseases and COVID-19 within a time frame of two years (between 15 March 2020 and 15 March 2022). Characteristics of the affected persons, as well as the risk factors for a fatal outcome, were analyzed. RESULTS: Of the 80 subjects in the study, 23.8% had chronic viral hepatitis, 12.5% autoimmune liver diseases and alcoholic liver disease respectively, 30% had non-alcoholic fatty liver disease, while 11.2% had chronic liver diseases of unknown aetiology. A total of 33.7% had cirrhosis, 6.3% hepatocellular carcinoma and 5% had liver transplants. A total of 92.5% of respondents had pneumonia (21.2% were critically ill). A deterioration of chronic liver disease was registered among 33.7% of patients, and decompensation in 3.8%; 76.3% patients recovered, while 23.7% had a lethal outcome. Risk factors for lethal outcome by univariate analysis were: alcoholic liver disease, cirrhosis, increased transaminases values prior to COVID-19, malignancy, severe pneumonia and dyspnea. In a multivariate analysis, the presence of liver cirrhosis (OR = 69.1, p = 0.001) and severe pneumonia (OR = 22.3, p = 0.006) remained independently predictive for lethal outcome. CONCLUSION: These findings will help with the evaluation of COVID-19 patients who have chronic liver diseases and will improve their risk stratification.

A single-center experience of early administration of tocilizumab and corticosteroids in patients with COVID-19 pneumonia.

BACKGROUND: We investigated the therapeutic response of tocilizumab (TCZ) therapy in patients with coronavirus disease 2019 (COVID-19) pneumonia. METHODS: This observational retrospective study included 205 patients with confirmed COVID-19 pneumonia with SpO2˂93% and a markedly increased level of at least two biomarkers of inflammation. The TCZ was given in combination with corticosteroids. Clinical and laboratory results were analyzed and compared before TCZ therapy and 7 d after. RESULTS: The mean value of C-reactive protein (CRP) was significantly lower (p=0.001) on the seventh day after administration of TCZ compared with before (10.7 and 173.6 mg/L, respectively). Only in 9/205 (4.3%) patients, the CRP level did not decrease during the week-long period, and this was related to disease progression. The mean level of interleukin-6 before TCZ administration was 88±113 pg/mL, while after it was 32.7±21.7 pg/mL (p=0.01). After 7 d of TCZ therapy, almost 50% of patients who needed high-flow oxygen or ventilation support started to receive low-flow oxygen, while 73/205 (35.6%) patients who received low-flow oxygen before TCZ administration did not receive further oxygen support anymore (p=0.001). Although they received TCZ treatment, 38/205 (18.5%) severely sick patients died. CONCLUSIONS: Tocilizumab improves clinical outcomes in hospitalized COVID-19 patients. These advantages were evident independent of the patient's comorbidities and were in addition to the advantages of systemic corticosteroids. In COVID-19 patients at risk of cytokine storms, TCZ appears to be an effective therapy choice.

Antioxidant Genetic Profile Modifies Probability of Developing Neurological Sequelae in Long-COVID.

Understanding the sequelae of COVID-19 is of utmost importance. Neuroinflammation and disturbed redox homeostasis are suggested as prevailing underlying mechanisms in neurological sequelae propagation in long-COVID. We aimed to investigate whether variations in antioxidant genetic profile might be associated with neurological sequelae in long-COVID. Neurological examination and antioxidant genetic profile (SOD2, GPXs and GSTs) determination, as well as, genotype analysis of Nrf2 and ACE2, were conducted on 167 COVID-19 patients. Polymorphisms were determined by the appropriate PCR methods. Only polymorphisms in GSTP1AB and GSTO1 were independently associated with long-COVID manifestations. Indeed, individuals carrying GSTP1 Val or GSTO1 Asp allele exhibited lower odds of long-COVID myalgia development, both independently and in combination. Furthermore, the combined presence of GSTP1 Ile and GSTO1 Ala alleles exhibited cumulative risk regarding long-COVID myalgia in carriers of the combined GPX1 LeuLeu/GPX3 CC genotype. Moreover, individuals carrying combined GSTM1-null/GPX1LeuLeu genotype were more prone to developing long-COVID "brain fog", while this probability further enlarged if the Nrf2 A allele was also present. The fact that certain genetic variants of antioxidant enzymes, independently or in combination, affect the probability of long-COVID manifestations, further emphasizes the involvement of genetic susceptibility when SARS-CoV-2 infection is initiated in the host cells, and also months after.

SOD2 rs4880 and GPX1 rs1050450 polymorphisms do not confer risk of COVID-19, but influence inflammation or coagulation parameters in Serbian cohort.

Objectives: Due to the role of oxidative stress in the pathophysiology of COVID-19, it is biologically plausible that inter-individual differences in patients' clinical manifestations might be affected by antioxidant genetic profile. The aim of our study was to assess the distribution of antioxidant genetic polymorphisms Nrf2 rs6721961, SOD2 rs4880, GPX1 rs1050450, GPX3 rs8177412, and GSTP1 (rs1695 and rs1138272) haplotype in COVID-19 patients and controls, with special emphasis on their association with laboratory biochemical parameters.Methods: The antioxidant genetic polymorphisms were assessed by appropriate PCR methods in 229 COVID-19 patients and 229 matched healthy individuals.Results: Among examined polymorphisms, only GSTP1 haplotype was associated with COVID-19 risk (p = 0.009). Polymorphisms of SOD2 and GPX1 influenced COVID-19 patients' laboratory biochemical profile: SOD2*Val allele was associated with increased levels of fibrinogen (p = 0.040) and ferritin (p = 0.033), whereas GPX1*Leu allele was associated with D-dimmer (p = 0.009).Discussion: Our findings regarding the influence of SOD2 and GPX1 polymorphisms on inflammation and coagulation parameters might be of clinical importance. If confirmed in larger cohorts, these developments could provide a more personalized approach for better recognition of patients prone to thrombosis and those for the need of targeted antiox-idant therapy.

GSTO1, GSTO2 and ACE2 Polymorphisms Modify Susceptibility to Developing COVID-19.

Based on the close relationship between dysregulation of redox homeostasis and immune response in SARS-CoV-2 infection, we proposed a possible modifying role of ACE2 and glutathione transferase omega (GSTO) polymorphisms in the individual propensity towards the development of clinical manifestations in COVID-19. The distribution of polymorphisms in ACE2 (rs4646116), GSTO1 (rs4925) and GSTO2 (rs156697) were assessed in 255 COVID-19 patients and 236 matched healthy individuals, emphasizing their individual and haplotype effects on disease development and severity. Polymorphisms were determined by the appropriate qPCR method. The data obtained showed that individuals carrying variant GSTO1*AA and variant GSTO2*GG genotypes exhibit higher odds of COVID-19 development, contrary to ones carrying referent alleles (p = 0.044, p = 0.002, respectively). These findings are confirmed by haplotype analysis. Carriers of H2 haplotype, comprising GSTO1*A and GSTO2*G variant alleles were at 2-fold increased risk of COVID-19 development (p = 0.002). Although ACE2 (rs4646116) polymorphism did not exhibit a statistically significant effect on COVID-19 risk (p = 0.100), the risk of COVID-19 development gradually increased with the presence of each additional risk-associated genotype. Further studies are needed to clarify the specific roles of glutathione transferases omega in innate immune response and vitamin C homeostasis once the SARS-CoV-2 infection is initiated in the host cell.

Seroprevalence of SARS-CoV-2 antibodies among primary healthcare workers in the Republic of Srpska, Bosnia & Herzegovina: A cross-sectional study.

Healthcare workers (HCW) in primary healthcare centres in the Republic of Srpska, Bosnia and Herzegovina, are on the first combat line with COVID-19. This study aimed to assess the seroprevalence of SARS-CoV-2 among HCW at the primary healthcare centres and to analyse the risk exposure to COVID-19, clinical signs and vaccination status. A cross-sectional study was conducted among HCW at the selected primary healthcare centres between 19 March and 30 April 2021. Antibodies against the SARS-CoV-2 virus were detected by enzyme-linked immunosorbent assay (ELISA). A total of 1,023 HCW (mean age 45 years; 71% female) were included in the study. The anti-SARS-CoV-2 antibodies were detected in 69.5% of all participants. There was a significant difference in seropositivity among primary healthcare centres from different geographical regions. As many as 432 (42%) of all participants had confirmed COVID-19 symptoms before the study and, 84.8% of them were seropositive. This study showed that 702 primary HCW were vaccinated with any of these vaccines: Sputnik V, Sinopharm, Pfizer/Biontech. High titre of SARS-CoV-2 antibodies was found amongst those who received one (92.6%) or both (97.2%) doses of vaccines. In this study, we report high prevalence of SARS-CoV-2 antibody among HCW in primary healthcare in the Republic of Srpska, Bosnia and Herzegovina during the third pandemic wave.

Validation and the Reliability of the ACIC Questionnaire in the Primary Health Care Setting: a Study from Bosnia and Herzegovina.

OBJECTIVE: The aim of this study was to carry out the cultural adaptation and validation of the Assessment of Chronic Illness Care questionnaire (ACIC) in the Republika Srpska, Bosnia and Herzegovina. METHODS: A validation study was conducted in two randomly selected primary health care centers in the Republika Srpska, Bosnia and Herzegovina, during March and April 2016. The study participants were all physicians working in family medicine departments during the study. Translation of the ACIC questionnaire version 3.5 was performed following the guidelines of the World Health Organization. The validity and reliability of the questionnaire were tested with face validity, construct validity, and internal consistency. RESULTS: The questionnaire was distributed to 66 family physicians. Missing values were negligible, therefore the criteria for factor analysis were met. Exploratory factor analysis confirmed that the questionnaire measured one factor. The Cronbach alpha coefficient (0.970) showed the excellent level of internal consistency of the questionnaire. The intraclass correlation coefficient (0.802) confirmed the good reliability of the questionnaire. CONCLUSION: The ACIC questionnaire can be used to assess the quality of chronic care in family medicine practice in Bosnia and Herzegovina. Further research is needed to explore how changes in healthcare care delivery impact changes in the Chronic Care Model domain.

The Influence of Different Risk Factors on COVID-19 Outcomes in Adult Patients - An Observational-Descriptive Study.

OBJECTIVE: The aim of our study was to investigate the predictors of morbidity (age, gender, smoking habits, obesity and the presence of chronic diseases) and COVID-19 outcomes. SUBJECTS AND METHODS: The research was an observational descriptive study, conducted at The Family Medicine Education Center, The Primary Health Care Center, Banja Luka, in the period from 26th June to 31st December 2020. During the research period, seven family medicine teams followed their patients with COVID- 19, and recorded possible predictors for morbidity and their influence on the disease outcome. RESULTS: The study included 934 patients, 46.90% of whom were male. The majority of subjects were non-smokers and overweight. Diabetes was found in 5.57% patients, hypertension in 29.44%, chronic respiratory diseases in 5.25%, cancer in 4.39% patients. In the observed sample, 29.23% subjects contracted pneumonia, 18.52% were hospitalized, while 19 (2.03%) patients with severe clinical features had a fatal outcome. Multivariable regression analysis showed a high risk of pneumonia in male patients [OR=2.45, 95% CI (1.73- 3.46)], elderly [OR=1.07, 95% CI (1.06-1.09)] and obese patients with Body Mass Index ≥30.0 kg/m2 [OR=2.55, 95% CI (1.73- 3.77)]. Male gender [OR=2.19, 95% CI (1.11-4.31)], older age [OR=1.08, 95% CI (1.05-1.11)] and hypertension [OR=2.51, 95% CI (1.06-5.91)] were the most important predictors for the development of severe clinical features in COVID 19. The statistically significant predictors of mortality were male gender [OR=7.16, 95% CI (1.56-32.86)] and older age [OR=1.12, 95% CI (1.06-1.18]. CONCLUSION: Being familiar with the predictors of morbidity and poor outcome in COVID-19 is helpful for carrying out preventive measures, early diagnosis and treatment of risk groups of patients.

GSTP1 and GSTM3 Variant Alleles Affect Susceptibility and Severity of COVID-19.

Based on the premise that oxidative stress plays an important role in severe acute respiratory syndrome coronavirus (SARS-CoV-2) infection, we speculated that variations in the antioxidant activities of different members of the glutathione S-transferase family of enzymes might modulate individual susceptibility towards development of clinical manifestations in COVID-19. The distribution of polymorphisms in cytosolic glutathione S-transferases GSTA1, GSTM1, GSTM3, GSTP1 (rs1695 and rs1138272), and GSTT1 were assessed in 207 COVID-19 patients and 252 matched healthy individuals, emphasizing their individual and cumulative effect in disease development and severity. GST polymorphisms were determined by appropriate PCR methods. Among six GST polymorphisms analyzed in this study, GSTP1 rs1695 and GSTM3 were found to be associated with COVID-19. Indeed, the data obtained showed that individuals carrying variant GSTP1-Val allele exhibit lower odds of COVID-19 development (p = 0.002), contrary to carriers of variant GSTM3-CC genotype which have higher odds for COVID-19 (p = 0.024). Moreover, combined GSTP1 (rs1138272 and rs1695) and GSTM3 genotype exhibited cumulative risk regarding both COVID-19 occurrence and COVID-19 severity (p = 0.001 and p = 0.025, respectively). Further studies are needed to clarify the exact roles of specific glutathione S-transferases once the SARS-CoV-2 infection is initiated in the host cell.

Health Literacy: Current Status and Challenges in the Work of Family Doctors in Bosnia and Herzegovina.

Health literacy (HL) has become an important area of research. The aim of this study was to evaluate the HL of primary healthcare patients in the Republic of Srpska (RS), Bosnia and Herzegovina (B&H) and to identify socioeconomic and health factors associated with HL. This cross-sectional study among 768 patients was conducted in two healthcare centres between March and May 2017, using the Short Test of Functional Health Literacy in Adults (S-TOFHLA). Analysis was done using descriptive and inferential statistics (a chi-squared test and logistic regression). Inadequate and marginal HL was found in 34,6% of respondents. Socioeconomic and self-reported health factors were significantly related to HL. An age of 55 years and over (OR 1.02), living in a rural environment (OR 2.25), being divorced (OR 3.32), being insufficiently physically active (OR 1.29), having poor income (OR 1.96), having more than three chronic diseases (OR 1.94), and poor health (OR 1.59) were significantly corelated with inadequate and marginal HL. The results of our study indicate that a low level of HL is related to the elderly, having a divorce, having a rural residence, poor income, having more than three chronic diseases, poor health, and insufficient physical activity. Further evaluation, monitoring, and activities to improve HL are of great importance for patients' health outcomes.

Assessment of health literacy in the adult population registered to family medicine physicians in the Republic of Srpska, Bosnia and Herzegovina.

BACKGROUND: Health literacy is an important determinant of health. This concept is under-researched in the Republic of Srpska, Bosnia and Herzegovina. OBJECTIVES: To assess health literacy and its association with sociodemographic variables, self-perception of health and the presence of chronic conditions in primary healthcare setting. METHODS: In May 2016, a cross-sectional study was executed in two primary healthcare centres. Out of approximately 1500 patients who visited both health centres during four consecutive days, about 800 were eligible. Of these, 110 patients agreed to complete the translated Short Test of Functional Health Literacy in Adults (S-TOFHLA). The influence of demographic, social, economic, and health characteristics (independent variables) on the S-TOFHLA score (dependent variable) was assessed by multiple logistic regression analysis. RESULTS: One questionnaire was incomplete and therefore 109 questionnaires were analysed. Inadequate, marginal, and adequate health literacy were present in 19 (17.4%), 16 (14.7%) and 74 (67.9%) respondents. Adequate health literacy was found predominantly among respondents younger than 55 years and those with a high level of education. Regression analyses showed that low level of education (OR: 5.3), age 55 years and over (OR: 3.9), living in a rural area (OR: 3.7) and having three or more chronic diseases (OR: 2) were independently associated with inadequate or marginal health literacy. CONCLUSION: In this study performed in two primary healthcare centres in the Republic of Srpska, Bosnia and Herzegovina, low health literacy was associated with low level of education, older age, living in a rural area, and having more chronic diseases.

Subregion-specific Protective Effects of Fluoxetine and Clozapine on Parvalbumin Expression in Medial Prefrontal Cortex of Chronically Isolated Rats.

Dysregulation of GABAergic system is becoming increasingly associated with depression, psychiatric disorder that imposes severe clinical, social and economic burden. Special attention is paid to the fast-spiking parvalbumin-positive (PV+) interneurons, GABAergic neurons which are highly susceptible to redox dysregulation and oxidative stress and implicated in a variety of psychiatric diseases. Here we analyzed the number of PV+ and cleaved caspase-3-positive (CC3+) cells in the rat medial prefrontal cortical (mPFC) subregions following chronic social isolation (CSIS), an animal model of depression and schizophrenia. Also, we examined potential protective effects of antidepressant fluoxetine (FLX) and atypical antipsychotic clozapine (CLZ) on the number of these cells in mPFC subregions, when applied parallel with CSIS in doses that correspond to therapeutically effective ones in patients. Immunofluorescence analysis revealed decreased number of PV+ cells in cingulate cortex area 1, prelimbic area (PrL), infralimbic area (IL) and dorsal peduncular cortex of the mPFC in isolated rats, which coincided with depressive- and anxiety-like behaviors. In addition, CSIS-induced increase in the number of CC3+ cells was detected in aforementioned subregions of mPFC. Treatments with either FLX or CLZ prevented behavioral changes, decrease in PV+ and increase in CC3+ cell numbers in PrL and IL subregions in isolated rats. These results indicate the importance of intact GABAergic signaling in these areas for resistance against CSIS-induced behavioral changes, as well as subregion-specific protective effects of FLX and CLZ in mPFC of CSIS rats.

Antioxidant Activity of Selected Polyphenolics in Yeast Cells: The Case Study of Montenegrin Merlot Wine.

Screens of antioxidant activity (AA) of various natural products have been a focus of the research community worldwide. This work aimed to differentiate selected samples of Merlot wines originated from Montenegro, with regard to phenolic profile and antioxidant capacity studied by survival rate, total sulfhydryl groups and activities of glutathione peroxidase (GPx), glutathione reductase and catalase in H2O2⁻stressed Saccharomyces cerevisiae cells. In this study, DPPH assay was also performed. Higher total phenolic content leads to an enhanced AA under both conditions. The same trend was observed for catechin and gallic acid, the most abundant phenolics in the examined wine samples. Finally, the findings of an Artificial Neural Network (ANN) model were in a good agreement (r² = 0.978) with the experimental data. All tested samples exhibited a protective effect in H2O2⁻stressed yeast cells. Pre-treatment with examined wines increased survival in H2O2⁻stressed cells and shifted antioxidative defense towards GPx⁻mediated defense. Finally, sensitivity analysis of obtained ANN model highlights the complexity of the impact that variations in the concentrations of specific phenolic components have on the antioxidant defense system.