Significance of Duodenal Prolactin Receptor Modulation by Calcium and Vitamin D in Sulpiride-Induced Hyperprolactinemia.

Background and Objectives: Hyperprolactinemia, as a potential side-effect of some antipsychotic medications, is associated with decreased bone density and an increased risk of fractures. This study investigates whether calcium and vitamin D supplementation affects prolactin receptor (Prlr) gene expression in the duodenum, vertebrae, and kidneys of female rats with sulpiride-induced hyperprolactinemia. Materials and Methods: Twenty-one-week-old female Wistar rats were assigned to three groups: Group S consisted of ten rats who received sulpiride injections (10 mg/kg) twice daily for 6 weeks; Group D (10 rats) received daily supplementation of 50 mg calcium and 500 IU vitamin D along with sulpiride for the last 3 weeks; and Group C consisting of seven age-matched nulliparous rats serving as a control group. Real-time PCR was used to assess Prlr gene expression in the duodenum, vertebrae, and kidneys. Results: In Group S, Prlr gene expression was notably decreased in the duodenum (p < 0.01) but elevated in the vertebrae and kidneys compared to Group C. Conversely, Group D exhibited significantly increased Prlr expression in the duodenum (p < 0.01) alongside elevated expression in the vertebrae and kidneys. Conclusions: In sulpiride-induced hyperprolactinemia, decreased Prlr gene expression in the duodenum may lead to reduced intestinal calcium absorption. Consequently, prolactin may draw calcium from the skeletal system to maintain calcium balance, facilitated by increased Prlr gene expression in the vertebrae. However, vitamin D supplementation in sulpiride-induced hyperprolactinemia notably enhances Prlr gene expression in the duodenum, potentially ameliorating intestinal calcium absorption and mitigating adverse effects on bone health.

Factors Associated with Length of Hospitalization in Patients with Diabetes and Mild COVID-19: Experiences from a Tertiary University Center in Serbia.

Background and Objectives: During the COVID-19 pandemic, there was an increased number of hospitalized COVID-19-positive patients suffering from type 2 diabetes mellitus (T2DM). The objective of this research study was to explore factors associated with the length of hospitalization of patients with T2DM and the mild form of COVID-19. Material and Methods: This retrospective cohort study involved all patients who tested positive for COVID-19 and those who were treated in the dedicated COVID-19 department of the University Clinical Center (UCC) in Nis between 10 September 2021 and 31 December 2021. Upon admission, patients underwent blood tests for biochemical analysis, including blood count, kidney and liver function parameters (C-reactive protein (CRP), creatinine kinase, and D-dimer), and glycemia and HbA1c assessments. Additionally, all patients underwent lung radiography. Univariate and multivariate regression analyses were employed to assess the impact of specific factors on the length of hospitalization among patients with T2DM. Results: Out of a total of 549 treated COVID-19-positive patients, 124 (21.0%) had T2DM, while 470 (79.0%) did not have diabetes. Among patients with T2DM, men were significantly younger than women (60.6 ± 16.8 vs. 64.2 ± 15.3, p < 0.01). The average hospitalization length of patients with diabetes was 20.2 ± 9.6 (5 to 54 days), and it was significantly longer than for patients without diabetes, at 15.0 ± 3.4, which ranged from 3 days to 39 (t-test ≈ 5.86, p < 0.05). According to the results of the univariate regression analysis, each year of age is associated with an increase in the length of hospital stay of 0.06 days (95% CI: 0.024 to 0.128, p = 0.004). Patients who received oxygen therapy were treated for 2.8 days longer than those who did not receive oxygen treatment (95% CI: 0.687 to 4988, p = 0.010), and each one-unit increase in CRP level was associated with a 0.02-day reduction in the length of hospitalization (95% CI: 0.004 to 0.029, p = 0.008). Based on the results of the multivariate regression analysis, each year of age is associated with an increase in the length of hospitalization by 0.07 days (95% CI: 0.022 to 0.110, p = 0.003). Patients who received oxygen therapy were treated for 3.2 days longer than those who did not receive oxygen therapy (95% CI: 0.653 to 5726, p = 0.014), and each unit increase in CRP level was associated with a 0.02-day reduction in the length of hospitalization (95% CI: 0.005 to 0.028, p = 0.004). Conclusions: Based on the presented results, COVID-19-positive patients with diabetes had, on average, longer hospitalizations than COVID-19 patients without diabetes. The hospital treatment of patients with T2DM and a milder form of COVID-19 was associated with older age, the use of oxygen therapy, and elevated CRP values. Patients who received oxygen therapy were treated approximately 3 days longer than those who did not receive this therapy.

Relationship between socio-descriptive characteristics, burnout syndrome, and quality of life of employees.

Introduction: Burnout syndrome develops as a consequence of chronic stress among employees. The study objective was to examine what socio-descriptive characteristics of employees might be associated with the appearance of the occupational burnout and to evaluate the relationship between job burnout and the quality of life among security employees of the professional private security sector in Central Serbia. Methods: A multicenter cross-sectional questionnaire-based study was performed. A multivariate logistic regression analysis and ANOVA post choc test was applied. Results: A total of 353 respondents (330 male and 23 female) participated in the study. Female sex and older age were associated with a higher risk of total burnout and the development of emotional exhaustion while male sex, higher education, and managerial position were associated with higher personal achievement and lower risk of total burnout. Male sex, marital union, two or more children, and direct contact with clients were significantly associated with a lower quality of life of employees. A significant negative correlation was found between total burnout and the Physical Health Composite Score (PHC) score with a correlation coefficient (rs) of -0.265 (95%CI from -0.361 to -0.163); between total burnout and the and Mental Health Composite Score (MHC) score with a rs of -0.391 (95%CI from -0.480 to -0.301); and between total burnout and TQL score with a rs of -0.351 (95%CI from -0.445 to -0.258). Conclusion: Female sex and older age were associated with a higher risk of total burnout and the development of EE while a managerial position and higher education were protective factors in relation to the development of burnout. Male sex, marital union, two or more children, and direct contact with clients were significantly associated with a lower quality of life of the employees. Shift work significantly reduced the total quality of life, while managerial positions increased the quality of life.

Clinical Benefit of Insulin Glargine 300 U/mL Among Patients with Type 2 Diabetes Mellitus Previously Uncontrolled on Basal or Premixed Insulin in Serbia: A Prospective, Observational, Single-Arm, Multicenter, Real-World Study.

INTRODUCTION: Insulin glargine 300 U/mL (Gla-300) is a novel glargine formulation which shows slower and more prolonged absorption following subcutaneous administration in comparison to insulin glargine 100 U/mL. In this prospective, observational, single-arm, multicenter, real-world study conducted in Serbia, we evaluated the effectiveness and safety of Gla-300 in patients with type 2 diabetes mellitus (T2DM) previously inadequately controlled with different basal or premix insulin therapy regimes. METHODS: A total of 350 patients with T2DM were enrolled by 27 physicians, from date of the first patient in (12 December 2017) to the date of last patient completed/last patient out (30 October 2018), from both medical centers and general hospitals. Patients' observation and data collection were performed at visit 1 (V1), i.e., the inclusion visit (3-6 months after Gla-300 introduction), including collection of retrospective data from the patients' medical charts at the time of Gla-300 introduction, and at visit 2 (V2) (3-6 months after V1). The primary objective was to assess the change in glycated hemoglobin (HbA1c) level from day of the Gla-300 initiation to the end of the observational period, while the secondary objectives included other effectiveness, as well as safety and other clinically relevant data. RESULTS: The mean age of the 350 patients was 63.4 ± 8.4 years and 56.3% were female. The mean duration of diabetes was 13.4 ± 7.4 years, while the mean duration of insulin therapy prior to Gla-300 initiation was 5.3 ± 3.9 years. There was a significant reduction in HbA1c level at each visit compared to the previous visit (8.63 ± 1.52% at baseline prior to Gla-300 initiation, 7.87 ± 1.13% at V1, 7.45 ± 1.05% at V2; p < 0.01 vs. previous visit) accompanied by significant reduction of all hypoglycemic events (p < 0.01). CONCLUSION: Initiation of Gla-300 therapy significantly improved glycemic control and reduced the risk of hypoglycemia in patients with T2DM inadequately controlled with different basal or premix insulin therapy regimes. FUNDING: Sanofi Serbia.

Recurrent Vulvovaginal Candidosis and Cluster Analysis of Clinical Signs and Symptoms: A Laboratory-Based Investigation.

Recurrent vulvovaginal candidosis (RVVC) represents a major health problem that significantly affects a patient's quality of life (QoL). This infection presents with a plethora of clinical manifestation, and this is the first study that carries out a cluster analysis of these signs and symptoms (SS). The goals are to evaluate the distribution of species causing RVVC, their in-vitro susceptibility to antifungals, and the patient's QoL. Additionally, the clinical characteristics are analyzed using cluster analysis. Prospective analysis of data was performed for women diagnosed with RVVC in the period from January 2016 to December 2019 based on the analysis of data from a single-center's records. The standard mycological methods and antifungal susceptibility testing were done. Clinical characteristics and QoL were examined by appropriate questions. The cluster analysis was used to identify clusters of SS. A total of 320 women were diagnosed. The dominant species was Candida (C.) albicans. Non-albicans Candida (NAC) yeast was found in 24.4%, and the most common was C. glabrata. Interestingly, Saccharomyces (S.) cerevisiae was detected in 2%. All of the isolated species, except C. parapsilosis and C. kefyr, demonstrated reduced susceptibility to antifungals. We confirmed the emergence of the NAC species and S. cerevisiae with reduced susceptibility to antifungals. Cluster analysis represented by a dendrogram revealed three SS clusters: irritation, uncommon, and discharge, but further studies are needed to examine the relationship between clusters, Candida strains, and outcomes.

Antibacterial Investigation of Thyme Essential Oil and Its Main Constituents in Combination with Tetracycline.

The chemical composition and antibacterial activity of Thymus glabrescens Willd. (thyme) essential oil were examined, as well as its association with tetracycline. The antibacterial activities of geraniol and thymol, the main constituents of T. glabrescens oil, were also determined. Gas chromatography and gas chromatography/mass spectrometry were used to analyze the chemical composition of the oil. The antibacterial activities of the oil, geraniol, and thymol were investigated by the broth microdilution method. The interactions of the essential oil, geraniol, and thymol with tetracycline, toward five selected strains, were evaluated using the microdilution checkerboard assay. Oxygenated monoterpenes were the most abundant compound class in the oil (57.14%), with geraniol (22.33%) as the major compound. The essential oil exhibited in vitro antibacterial activity against all tested bacterial strains. The combinations, essential oil-tetracycline and thymol-tetracycline, produced synergistic interaction to a greater extent compared with geraniol-tetracycline association. All synergistic combinations reduced the minimum effective dose of the antibiotic and, consequently, minimized its adverse side effects.

Pseudomonas aeruginosa serotypes and resistance to antibiotics from wound swabs.

INTRODUCTION/AIM: Pseudomonas aeruginosa (P. aeruginosa) is the most common cause of wound infections, following the disruption of the skin or mucous membranes integrity. The aim of this study was to analyze of the presence P. aeruginosa in wound swabs, antibiotics susceptibility testing, determination of the minimum inhibitory concentrations (MICs) of antibiotics, testing of the metallo-ß-lactamases (MBLs) production, isolates serotyping and analysis of the most common serotypes resistance. METHODS: A total of 90 outpatients and 55 intpatients wound swabs were cultivated. Wound swabs were taken from the patients with wound infections symptoms. Antibiotics susceptibility testing was performed to: meropenem, imipenem, piperacillin-tazobactam, ceftazidime, cefepime, amikacin, gentamicin, netilmicin, of loxacin, ciprofloxacin and colistin (HiMedia). Polyvalent and monovalent antisera for agglutination (Biorad) were used in P. aeruginosa agglutination. RESULTS: P. aeruginosa was isolated from 36.55% wound swabs (36.66% of the inpatients wounds and 36.36% of the outpatients). The analyzed isolates showed the highest degree of sensitivity to colistin (100%) and meropenem (93.44%) and the lowest to cefepime (19.54%). The majority of the inpatients isolates had 12 µg/mL (28.57%) MIC for piperacillin-tazobactam and 16 µg/ml (28.57%) for the outpatients. The most common MICs for ciprofloxacin were 0.19 µg/mL (31.81%) for the nosocomial isolates, and 0.25 µg/mL (28.57%) for the outpatients' ones. The most common ICs for amikacin of the nosocomial isolates were 6 µg/ml (40.90%), and for the outpatients ones 4 µg/mL (33.33%). Five (9.43%) isolates produced MBLs. The most common serotypes were P11 (22.64%), P6 (15.09%) and P1 (11.32%). CONCLUSION: Neither the increased presence of P. aeruginosa was noticed in wounds swabs, nor the antibiotic resistance in the nosocomial isolates compared to those from outpatients. The analyzed isolates had the higest sensitivity to colistin and meropenem, and the lowest to cefepime.

An in vitro synergistic interaction of combinations of Thymus glabrescens essential oil and its main constituents with chloramphenicol.

The chemical composition and antibacterial activity of Thymus glabrescens Willd. (Lamiaceae) essential oil were examined, as well as the association between it and chloramphenicol. The antibacterial activities of geraniol and thymol, the main constituents of T. glabrescens oil, individually and in combination with chloramphenicol, were also determined. The interactions of the essential oil, geraniol, and thymol with chloramphenicol toward five selected strains were evaluated using the microdilution checkerboard assay in combination with chemometric methods. Oxygenated monoterpenes were the most abundant compound class in the oil, with geraniol (22.33%) as the major compound. The essential oil exhibited in vitro antibacterial activity against all tested bacterial strains, but the activities were lower than those of the standard antibiotic and thymol. A combination of T. glabrescens oil and chloramphenicol produced a strong synergistic interaction (FIC indices in the range 0.21-0.87) and a substantial reduction of the MIC value of chloramphenicol, thus minimizing its adverse side effects. The combinations geraniol-chloramphenicol and thymol-chloramphenicol produced synergistic interaction to a greater extent, compared with essential oil-chloramphenicol association, which may indicate that the activity of the thyme oil could be attributed to the presence of significant concentrations of geraniol and thymol.

The hypertriglyceridemic waist phenotype and metabolic syndrome by differing criteria in type 2 diabetic patients and their relation to lipids and blood glucose control.

BACKGROUND: Metabolic syndrome (MetS) describes clustering of obesity, dyslipidemia, hyperglycemia and hypertension and increases risk for cardiovascular disease and type 2 diabetes. The 'hypertriglyceridemic waist' phenotype (HTGW) represents a simple approach to identifying individuals with increased risk. The aim of the study was to determine the prevalence of HTGW and MetS in type 2 diabetic patients, and to examine their relation to lipids and blood glucose control. MATERIAL AND METHODS: 300 type 2 diabetic patients were analysed, and their history of diabetes, anthropometric measures, measurements of blood pressure (BP), lipids and glycemic control parameters were taken. RESULTS: In type 2 diabetic patients, the prevalence of MetS was 71.0% by the AHA/NHLBI definition and 75.33% by the IDF definition. The prevalence was 62.58% and 66.45% in men, and 80% and 84.83% in women by the same definitions, respectively. There were 41.33% of patients with HTGW (42.76% among women and 40% among men). There were statistically significant differences of age, fasting plasma glucose (FPG) and postprandial glucose (PPG) in women with and without MetS according to both definitions, and of total and LDL cholesterol with and without MetS according to AHA/NHLBI (but not IDF). In men, there were statistically significant differences of total cholesterol and of HbA(1c) with and without MetS according to AHA/NHLBI (but not IDF). Women with HTGW had higher levels of total and LDL cholesterol, systolic and diastolic BP. Men with HTGW had higher levels of total cholesterol, diastolic BP, HbA(1c), FPG and PPG. CONCLUSIONS: Determining MetS or HTGW helps identify those with increased cardiovascular risk.

[New aspects about the impact of oxidative stress on development of chronic diabetic complications].

Oxidative stress is defined as a state when the free radical production ovecome their neutralisation via the antioxidative defense systems. Being extremely unstable, these molecules and ions tend to achieve a stable state by reacting with the surrounding molecules, which are immediately oxidised. Such chain reactions may have substantial effects on almost all cellular structures, including the lipids, the proteins and the nuclear DNA. LDL particles become atherogenic because their apoB is subjected to the oxidative modification, being recognized by the scavenger receptors. Type 2 diabetes represents a conformational disease in which proteins are subjected to the oxidative modification. The disease proceeds in several stages such as: the transition is the latent period where oxidatively modified proteins are deposited in the EPR structures, periods of accelerated redox stress when amyloid precursors are accumulated, accompanied with the insulin secretory deficiency. The process is aggravated by glycosylated proteins, which are the free radical producers. This complex cascade proceeds through the formation of early (Schiff bases and Amadori) products, while further glycation of proteins and lipids causes molecular rearrangements that lead to the generation of advanced glycation endproducts (AGEs). High glucose concentrations in non insulin-dependent tissues may follow the pathway of aldose reductase, when reduced nucleotides are used as the cofactors, leading to decreased reduced glutathione (GSH) content. Glucose fluctuations during postprandial periods exhibited a more specific triggering effect on free radical production. The superoxide overproduction is accompanied by an increased nitric oxide (NO) generation, a phenomenon favoring the formation of the stronger oxidant peroxynitrite. The increased free radical generation in accumulated fat causes dysregulated production of adipocytocines locally, leading to development of metabolic syndrome.

[Coagulase-negative Staphylococcus isolated from bloodculture--causes or contaminants?].

INTRODUCTION: According to the results of different investigations, the opinion that isolate of coagulase-negative staphylococci by bloodcultures represents the blood infection in 10-12% patient. The aim of the work was to determine the number of patients with blood infection-sepsa induced coagulase-negative staphylococci isolated by bloodcultures. MATERIAL AND METHODS: The research was done at the Institute for Public Health in Nis. The basic group consisted of 56 patients and coagulase-negative staphylococci were segregated form their bloodcultures. The growth of microorganisms was monitored by the computerized apparatus "Bactec 9120". Coagulase-negative staphylococci were identified by the standard microbiologic method and Vitec AMS system. RESULTS: Eight patients (14.28%) were found to have minimum two signs of blood infection. S. epidermis was isolated in four patients. S. saprophyticus was isolated in the patients on hemodialysis with implanted urinary catheter. S. capitis was isolated in the patients with infarctus miocardi. S. auricularis was isolated in child who was administered the immunosuppressive therapy before and during hospitalization due to an acute asthmatic attack. The isolate of S. simulans was cultivated from samples of the patients hospitalized due to the febrile state. DISCUSSION: A correct interpretation of coagulase-negative staphylococci findings in bloodcultures is an overriding part of medical treatment. The best laboratory indicators of the presence of coagulase-negative staphylococci in blood would be to segregate those of the same kind from two samples at the same time but from different anatomic sites in the presence of clinical signs of blood infection. CONCLUSION: In the investigation conducted at the Public Health Institute-Nis, we determined that bloodcultures isolated coagulase-negative staphylococci represent the blood infection on 14.28% patient.

Impact of diet, physical activity, lipid status and glycoregulation in estimation of score (systematic coronary risk evaluation) for ten years in postmenopausal women.

The incidence of cardiovascular diseases (CVD) in women, although lower than in men, increases dramatically after the menopause. Diabetes mellitus is a more powerful predictor of CHD risk and prognosis in women than in men. The aim of this study was to promote diet and physical activity (PA) regimen in order to decrease coronary risk in next years in postmenopausal women with impaired glucose tolerance. Methodological approach of this research is to compare data gathered trough prospective and retrospective analysis of anamnestic data, clinical research, diagnostic tests and biochemical parameters of 100 examinees, regarding the glycoregulation, lipid status, body mass indexes, incidence of hypertension, uric acid and fibrinogen level. The SCORE (Systematic Coronary Risk Evaluation) assessment system is derived from a large dataset of prospective European studies and predicts any kind of fatal CVD events over a ten-year period. It was documented that the then year risk of fatal CVD exerted a shift toward the lower percent value in postmenopausal women after proposed diet/PA regimen. In pre-menopausal women the estimated ten year risk of fatal CVD by SCORE was shifted toward the level below 1%. The risk of 15% and above was not documented after diet/physical activity regimen. The prevalence of the atherogenic lipid markers at the beginning and the end of the assay decreased for all investigated lipid parameters in the group of pre-menopausal women what was more than in postmenopausal ones. Presented data indicate that dietary regimen and physical activity are crucial factors in CVD prevention throughout menopause and beyond. Behavioral changes aimed at decreasing food intake and increasing energy expenditure, should be implemented in pre-menopausal period of life.