Klinički centar Niš

Chlamydiae replicate within an intracellular vacuole, termed an inclusion, that is non-fusogenic with vesicles of the endosomal or lysosomal compartments. Instead, the inclusion appears to intersect an exocytic pathway from which chlamydiae intercept sphingomyelin en route from the Golgi apparatus to the plasma membrane. Chlamydial protein synthesis is required to establish this interaction. In an effort to identify those chlamydial proteins controlling vesicle fusion, we have prepared polyclonal antibodies against several Chlamydia trachomatis inclusion membrane proteins. Microinjection of polyclonal antibodies against three C. trachomatis inclusion membrane proteins, IncA, F and G, into the cytosol of cells infected with C. trachomatis demonstrates reactivity with antigens on the cytoplasmic face of the inclusion membrane, without apparent inhibition of chlamydial multiplication. Microinjection of antibodies against the C. trachomatis IncA protein, however, results in the development of an aberrant multilobed inclusion structure remarkably similar to that of C. psittaci GPIC. These results suggest that the C. trachomatis IncA protein is involved in homotypic vesicle fusion and/or septation of the inclusion membrane that is believed to accompany bacterial cell division in C. psittaci. This proposal is corroborated by the expression of C. trachomatis and C. psittaci IncA in a yeast two-hybrid system to demonstrate C. trachomatis, but not C. psittaci, IncA interactions. Despite the inhibition of homotypic fusion of C. trachomatis inclusions, fusion of sphingomyelin-containing vesicles with the inclusion was not suppressed.

We have examined the effect of activated neutrophils on the release of prostacyclin (PGI2) from cultured endothelial cells by radioimmunoassay and thin layer chromatography of its stable metabolite, 6-keto-prostaglandin F1 alpha (6-keto-PGF1 alpha). Phorbol myristate acetate-activated neutrophils induced a time- and dose-dependent release of 6-keto-PGF1 alpha from human and bovine endothelial cell monolayers, whereas phorbol myristate acetate alone and neutrophils alone did not. Pretreatment of the endothelial cells with aspirin prevented neutrophil-mediated 6-keto-PGF1 alpha release, indicating that it did not depend upon neutrophil-generated endoperoxides. Phorbol myristate acetate-activated neutrophils from a patient with chronic granulomatous disease failed to induce endothelial 6-keto-PGF1 alpha release. Addition of catalase but not of superoxide dismutase significantly reduced human and bovine endothelial 6-keto-PGF1 alpha release by phorbol myristate acetate-activated neutrophils. Catalase-inhibitable endothelial 6-keto-PGF1 alpha release was also observed after the addition of the hydrogen peroxide-generating system, glucose-glucose oxidase, to bovine and human endothelial cell monolayers. Bovine endothelial 6-keto-PGF1 alpha release induced by exogenously generated hydrogen peroxide was attenuated by the phospholipase inhibitor mepacrine, suggesting that hydrogen peroxide may act by triggering endothelial membrane phospholipase activation. The release of 6-keto-PGF1 alpha by enzymatically or neutrophil-generated hydrogen peroxide was not associated with endothelial cell lysis as assessed by 51Cr release. We conclude that exogenously generated hydrogen peroxide or a hydrogen peroxide-derived product mediates rapid nonlytic release of PGI2 from cultured endothelial cells.

Autoimmunity occurs when T cells, B cells or both are inappropriately activated, resulting in damage to one or more organ systems. Normally, high-affinity self-reactive T and B cells are eliminated in the thymus and bone marrow through a process known as central immune tolerance. However, low-affinity self-reactive T and B cells escape central tolerance and enter the blood and tissues, where they are kept in check by complex and non-redundant peripheral tolerance mechanisms. Dysfunction or imbalance of the immune system can lead to autoimmunity, and thus elucidation of normal tolerance mechanisms has led to identification of therapeutic targets for treating autoimmune disease. In the past 15 years, a number of disease-modifying monoclonal antibodies and genetically engineered biologic agents targeting the immune system have been approved, notably for the treatment of rheumatoid arthritis, inflammatory bowel disease and psoriasis. Although these agents represent a major advance, effective therapy for other autoimmune conditions, such as type 1 diabetes, remain elusive and will likely require intervention aimed at multiple components of the immune system. To this end, approaches that manipulate cells ex vivo and harness their complex behaviors are being tested in preclinical and clinical settings. In addition, approved biologic agents are being examined in combination with one another and with cell-based therapies. Substantial development and regulatory hurdles must be overcome in order to successfully combine immunotherapeutic biologic agents. Nevertheless, such combinations might ultimately be necessary to control autoimmune disease manifestations and restore the tolerant state.

Nutrigenomic DNA reprogramming in different chronic diseases and cancer has been assessed through the stimulation of gene expression and mRNA synthesis versus DNA silencing by CpG DNA modification (methylation); histone modification (acetylation, methylation) and expression of small noncoding RNAs, known as microRNAs (miRNAs). With regard to the specific nutrigenomic effects in psoriasis, the influence of specific diets on inflammatory cell signaling transcriptional factors such as nuclear factor (NF)-κB and Wnt signaling pathways, on disease-related specific cytokine expression, pro/antioxidant balance, keratinocyte proliferation/apoptosis and on proliferation/differentiation ratio have been documented; however, the influence of dietary compounds on the balance between ‘good and bad’ miRNA expression has not been considered. This review aims to summarize knowledge about aberrant microRNAs expression in psoriasis and to emphasize the potential impact of some dietary compounds on endogenous miRNA synthesis in experimental conditions in vivo and in vitro. Among the aberrantly expressed miRNAs in psoriasis, one of the most prominently upregulated seems to be miR-21. The beneficial effects of phenolic compounds (curcumin and resveratrol), vitamin D, methyl donors, and omega-3 fatty acids (eicosapentaenoic acid and docosahexaenoic acid) are discussed. Highly expressed miR-155 has been downregulated by flavonoids (through a quercetin-rich diet) and by vitamin D. Quercetin has been effective in modulating miR-146a. On the other hand, downregulated miR-125b expression was restored by vitamin D, Coenzyme Q10 and by microelement selenium. In conclusion, the miRNA profile, together with other ‘omics’, may constitute a multifaceted approach to explore the impact of diet on psoriasis prevention and treatment.

OBJECTIVE: To review the audiologic results in a cohort of patients surgically treated for cholesteatoma. STUDY DESIGN: Retrospective review of patient records. SETTING: Tertiary referral center. PATIENTS: A retrospective study of patients operated on for acquired middle ear cholesteatoma during the period 1990 to 2002 was performed. A total of 758 patients were followed during a short-term period, and 611 patients were followed during a long-term period. The patients were divided into 3 age groups: children, adolescents, and adults. The localization of cholesteatoma was classified as attic, sinus, or tensa. INTERVENTIONS: Closed tympanoplasty was always performed as the single procedure of choice on all the children, and reoperation or conversion to open tympanoplasty was made later if needed. Adult patients were treated with single classic canal wall up, or wall down (CWD), according to the propagation of disease and condition of middle ear. MAIN OUTCOME MEASURES: Preoperative and postoperative air-bone gap (ABG) and pure-tone average were compared after short-term and long-term follow-up. RESULTS: Average hearing improvement (reduction of ABG) amounted 20.0 dB for short-term and deteriorated to 18.0 dB during long-term analysis for all the patients. Preoperative hearing level was significantly worse for CWD than for intact canal wall technique. The ABG closure was much better in the group with attic cholesteatoma. Both preoperative and postoperative hearing levels were worse for children than for adolescents or adults. Revision operations and bilateral cholesteatoma gave worse total postoperative hearing. The long-term results of primary operations, when recurrent cholesteatoma did not occur, were stable. Damage to auditory ossicles correlated well with total preoperative and postoperative results. The most hearing improvement was verified for the frequencies between 500 and 3,000 Hz, and there was no sensorineural hearing loss. CONCLUSION: The audiologic results of cholesteatoma surgery are preserved during long-term follow-up. We found that recurrent cholesteatoma was associated with diminished postoperative hearing. Poorer preoperative hearing level, CWD tympanoplasty, younger age, bilateral cholesteatoma, and ossicular damage, as well as revision surgery, were associated with reduced gains in hearing with surgical management. Surgical experience was important for ICW technique and for advanced damage of auditory ossicles. Recurrent cholesteatoma resulted in significantly worse hearing results for each analyzed parameter.

BACKGROUND: The aim of this study was to assess and compare patients' access to biologic anti-RA drugs in selected Central and Eastern European (CEE) countries and to analyze the determinants of differences between countries. MATERIAL/METHODS: This is a multi-country survey study, based on a combination of desk research and direct contact with national RA stakeholders. Data was collected using a pre-defined questionnaire. Affordability was measured using an affordability index, calculated comparing the index of health care expenditures to the price index, using Poland as an index of 1. RESULTS: The percentage of patients on biologic treatment in 2009 was highest in Hungary (5% RA patients on biologic treatment), followed by Slovenia (4.5%), Slovakia (3.5%), Czech Republic (2.92%), Romania (2.2%), Estonia (1.8%), and Croatia, Serbia, Poland (below 1.5%). Infliximab, etanercept, adalimumab and rituximab were included in the reimbursement system in all countries, but abatacept and tocilizumab were included only in Slovakia. In Slovenia, public payer covered 75% of the price, and 25% is covered by supplementary health insurance; in Bulgaria public payer covered 50% of etanercept and adalimumab costs, and 75% of rituximab cost. In other countries, biologic drugs are reimbursed at 100%. Affordability index for biologic drugs was the lowest in Slovenia (0.4). In each country national guidelines define which patients are eligible for biologic treatment. Disease Activity Score (DAS28) of over 5.1 and failure of 2 or more disease-modifying anti-RA drugs, including methotrexate, are commonly used criteria. CONCLUSIONS: The most important factors limiting access to biologic anti-RA treatment in the CEE region are macroeconomic conditions and restrictive treatment guidelines.

Background: The successful management of asthma and chronic obstructive pulmonary disease (COPD) mostly depends on adherence to inhalation drug therapy, the usage of which is commonly associated with many difficulties in real life. Improvement of patients’ adherence to inhalation technique could lead to a better outcome in the treatment of asthma and COPD. Objective: The aim of this study was to assess the utility of inhalation technique in clinical and functional control of asthma and COPD during a 3-month follow-up. Methods: A total of 312 patients with asthma or COPD who used dry powder Turbuhaler were enrolled in this observational study. During three visits (once a month), training in seven-step inhalation technique was given and it was practically demonstrated. Correctness of patients’ usage of inhaler was assessed in three visits by scoring each of the seven steps during administration of inhaler dose. Assessment of disease control was done at each visit and evaluated as: fully controlled, partially controlled, or uncontrolled. Patients’ subjective perception of the simplicity of inhalation technique, disease control, and quality of life were assessed by using specially designed questionnaires. Results: Significant improvement in inhalation technique was achieved after the third visit compared to the first one, as measured by the seven-step inhaler usage score (5.94 and 6.82, respectively; P <0.001). Improvement of disease control significantly increased from visit 1 to visit 2 (53.9% and 74.5%, respectively; P <0.001) and from visit 2 to visit 3 (74.5% and 77%, respectively; P <0.001). Patients’ subjective assessment of symptoms and quality of life significantly improved from visit 1 to visit 3 ( P <0.001). Conclusion: Adherence to inhalation therapy is one of the key factors of successful respiratory disease treatment. Therefore, health care professionals should insist on educational programs aimed at improving patients’ inhalation technique with different devices, resulting in better long-term disease control and improved quality of life. Keywords: Turbuhaler, adherence, inhalation technique, asthma, COPD

BACKGROUND: Numerous studies have suggested that 54%-100% of patients with IBS may have associated psychiatric illness and personality pathology. This transversal controlled study was realized in order to evaluate anxiety and depression levels, as well as the personality characteristics of patients with IBS and to compare the results obtained with patients with episodes of depression and healthy individuals. SUBJECTS AND METHODS: The experimental group consisted of 30 IBS patients, while two control groups consisted of the same number of inpatients with episodes of depression and healthy individuals from the general population. There were equal number of men and women in the study sample and all subjects were aged between 25 to 65 years. Standard psychometric instruments employed included Hamilton anxiety scale, Zung depression scale, Hamilton depression scale, Minnesota Multiphasic Personality Inventory (MMPI), Eysenck Perosonality Inventory (EPI). RESULTS: The average Hamilton and Zung depression scores were significantly higher in patients with depressive episodes compared with the IBS patients, while the mentioned scores among them were also significantly higher compared with the healthy controls. There were no significant differences between IBS and the group with depressive episodes in the average Hamilton anxiety levels, EPI neuroticism and extraversion levels and MMPI neurotic scales levels (Hs, D, and Hy). The significant differences were observed comparing the IBS patients to healthy individuals. CONCLUSION: The patients suffering from irritable bowel syndrome who asked for medical help (consulters) because of their intestinal symptoms, presented emotional problems such as depression and anxiety and expressed neurotic personality characteristics.

INTRODUCTION: The coronavirus disease 2019 (COVID-19) pandemic caused significant changes in the everyday functioning of the general population, as well as medical workers. Medical personnel, especially those in direct contact with COVID-19 patients, could have increased levels of stress, anxiety, and depression. The objective of this study was to explore the mental health status of medical personnel in Serbia during the pandemic by assessing stress levels, symptoms of anxiety, and depression. METHODS: This cross-sectional study was conducted as an online-based survey, in the period from 8 April to 14 April 2020, during the COVID-19 pandemic. The study included 1678 participants, and the snowball sampling technique was used to reach healthcare professionals. The level of stress and symptoms of depression and anxiety were assessed among medical personnel in Serbia by the 10-item Perceived Stress Scale (PSS), the Beck Depression Inventory IA (BDI-IA), and the 7-item Generalized Anxiety Disorder Scale (GAD-7), respectively. RESULTS: A total of 1678 participants completed the survey, with a mean age of 40.38 ± 10.32 years, of which 1,315 (78.4%) were women, and 363 (21.6%) were men. Out of these, 684 (40.8%) participants were medical personnel, and 994 (59.2%) were people of other professions. Frontline medical personnel reported higher scores on all measurement tools than second-line medical personnel (e.g., mean PSS scores: 19.12 ± 5.66 versus 17.53 ± 5.71; p = .006; mean GAD-7 scores: 8.57 ± 6.26 versus 6.73 ± 5.76; p = .001; mean BDI-IA scores: 9.25 ± 8.26 versus 7.36 ± 7.28; p = .006). Binary logistic regression showed that the probability of developing more severe anxiety symptoms doubles in frontline medical personnel. CONCLUSION: Our findings suggest that frontline medical personnel is under an increased psychological burden during the COVID-19 pandemic, having higher levels of stress, anxiety, and depression than second-line medical personnel. Adequate measures should be taken to relieve this burden and preserve the mental health of frontline medical personnel.

&amp;lt;p style=&amp;quot;text-align: justify;&amp;quot;&amp;gt;The presence of diabetes mellitus leads to a decrease in life quality in all domains. The aim of our study was to evaluate the quality of life (QOL) in diabetic patients and the factors affecting it in type 2 diabetic mellitus patients. We conducted a cross-sectional study that included 86 patients with type 2 diabetes mellitus, in the territory of the City of Ni&amp;amp;scaron;. Health-related QOL of patients was measured using the short form survey (SF-36) that produces an 8-scale health profile. The average duration of diabetes was 12.76 &amp;amp;plusmn; 8.08 years. The best QOL in all areas was observed in patients diagnosed with diabetes less than 10 years ago p &amp;amp;lt; 0.05) and younger than 65 years. Male respondents perceived a better QOL compared to women, especially in the vitality and pain domains. The patients with comorbidity (93.64%) had lower QOL score in all domains. There was no significant difference in the QOL of patients with diabetes compared to the level of education. High QOL represents an ultimate goal and an important outcome of all medical interventions in diabetic patients. Factors related to lower QOL included: older age, female gender, and existence of comorbidities. Uncontrolled diabetic patients had a lower QOL than controlled diabetics.&amp;lt;/p&amp;gt;

BACKGROUND: There are no universally accepted opinions about the choice of surgical technique and outcome of surgery for cholesteatoma in different age groups and localizations. METHODS: A prospective study of 758 patients with cholesteatomas was performed. They were divided into three age groups: children younger than 9 years, adolescents aged 10-16 years, and adults. Cholesteatoma was classified as: attic, sinus and tensa cholesteatoma. Classical canal wall-up or wall-down tympanoplasty was performed in all the cases, and reoperation was done later if needed. Anatomical and functional results were followed up regularly, and evaluated 3 years after the operations. RESULTS: During the postoperative course, after 3 years, retraction of the neomembrane was found in 23.8% of younger children, 27.6% of adolescents, and in 9.9% of adults. Recurrent cholesteatomas were more than twice as frequent in children (19.0%) as in adults (9.4%). Reoperation was performed in 38.1% of children and in 9.4% adults. In one fourth of pediatric cholesteatoma reoperations, conversion to open tympanoplasty was done. Retraction and recurrent disease were present in about 10% of attic and sinus cholesteatomas, and in 15.5% of tensa cholesteatomas. CONCLUSION: Postoperative audiological results of cholesteatoma surgery in children are comparable to adults. Retraction pockets, recurrent cholesteatomas and reoperations are twice as frequent in the pediatric group as in adults. The worst anatomical and functional results are achieved in tensa cholesteatomas. The age of the patient and localization of cholesteatoma are very important factors that determine the type of surgical procedure and the results of surgery for middle ear cholesteatoma. A closed technique is better for attic and sinus cholesteatomas, while in tensa cholesteatomas, an open technique seems more appropriate.

Although studies exploring relationships between obesity and cognitive impairment in the elderly are conflicting, literature suggests that overweight and obesity may be protective against cognitive impairment and dementia in older women. We examine the associations between changes in weight and waist circumference (WC) with global and domain-specific cognitive function in a large, well-defined cohort of 2,283 older, postmenopausal women (aged 65-79) prospectively followed through the Women's Health Initiative (WHI) Study of Cognitive Aging (WHISCA). We assessed the associations between changes in weight and WC collected up to 5 years before WHISCA enrollment and mean levels of global and domain-specific cognitive performance across an average of 5.4 years of subsequent follow-up. There was a lack of associations between weight and cognition in women who remained stable or gained weight. The only significant relationships observed were in association with weight loss (P ≤ 0.05), most likely signaling incipient disease. Moreover, cognition was not related to changes in WC. Relationships were largely independent of initial BMI, self-reported caloric intake or dieting. The lack of associations between weight gain and cognition in women is consistent with the existing literature.

INTRODUCTION: The manifestations of autonomic nervous system (ANS) dysfunction in autoimmune diseases have been the subject of many studies. However, the published results pertaining to such research are controversial. Sudden cardiac death due to fatal arrhythmias is frequent in patients with systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA). OBJECTIVE: To analyse risk predictors of sudden cardiac death related to the degree of autonomic dysfunction. METHODS: We performed cardiovascular ANS assessment in 90 patients in this case-controlled study, including 52 (6 male, 46 female) patients with SLE, 38 (6 male, 32 female) with RA and 41 (23 male, 17 female) healthy subjects. The methodology included a comprehensive ECG analysis (with Schiller software AT-10) of QTc interval, late potentials, short-term heart rate variability (HRV) and nonlinear HRV (Poincare plot) analysis; 24-hour Holter ECG monitoring with ECG QTc interval analysis, HRV analysis; 24-hour blood pressure monitoring with systolic and diastolic blood pressure variability; cardiovascular autonomic reflex tests (according to Ewing). Vagal dysfunction was established by performing 3 tests: Valsalva maneuver, deep breathing test and heart rate response to standing test. Dysfunction of the sympathetic nervous system was examined by applying 2 tests: blood pressure response to standing and handgrip test. RESULTS: In all cardiovascular reflex tests, the frequencies of abnormal results were significantly higher among the patients than among the healthy subjects. Severe autonomic dysfunction was more common in RA. QTc interval was more prolonged in patients with SLE. Both diseases were associated with depressed heart rate variability compared to controls, the reduction being greater in RA patients. In the patients with SLE, autonomic dysfunction is predominantly with higher sympathetic activity while in RA vagal predominance is evident. CONCLUSION: SLE and RA are associated with severe autonomic dysfunction and the presence of significant risk predictors related to the onset of sudden cardiac death.

ABSTRACT Each year, the amount of fish produced around the world increases, which contributes to several environmental impacts such as the disposal of effluents without treatment in the environment. This scientific work had as main objective the development of Spirulina platensis in fish effluents, a low cost medium for the production of biomass, in order to reduce the levels of some inorganic nutrients to reach the allowed parameters by the Brazilian environmental standards for effluent disposal and to enable reuse of the water. Nile tilapia (Oreochromis niloticus) fingerlings were produced in fresh water. The effluent generated by the culture was transferred to a pool where seawater was added until the salinity of 10 ‰ was reached. A strain of cyanobacteria, Spirulina platensis, was inserted into the mixture in order to remove the nutrients dissolved on the fish culture effluent. The abiotic parameters analyzed were: absorbance, pH, dissolved oxygen, temperature, salinity and concentrations of ammonia, nitrite, nitrate and phosphate. The results revealed that the maximum cellular density of S. platensis resulted in the production of 0.22 g L-1 of dry biomass and maximum productivity of 0.03 g L-1 day-1. The concentration of ammonia, nitrite, nitrate and phosphate got lowered by more than 94.8%, maintaining the nutrient levels within the standards those required by Brazilian environmental standards. Hence, this effluent has become adequate for reuse in fish production or could be safely disposed in nature.

BACKGROUND: There are diverse molecules present in blood plasma that regulate immune functions and also present a potential source of disease biomarkers and therapeutic targets. Genome-wide profiling has become a powerful method for assessing immune responses on a systems scale, but technologies that can measure the plasma proteome still face considerable challenges. An alternative approach to direct proteome assessment is to measure transcriptome responses in reporter cells exposed in vitro to plasma. In this report we describe such a "transcriptomic reporter assay" to assess plasma from patients with sepsis, which is a common and severe systemic infectious process for which physicians lack efficient diagnostic or prognostic markers. METHODS: Plasma samples collected from patients with culture-confirmed bacterial sepsis and uninfected healthy controls were used to stimulate three separate cell types - neutrophils, peripheral blood mononuclear cells, and monocyte-derived dendritic cells. Whole genome microarrays were generated from stimulated cells to assess transcriptional responses. Unsupervised analysis and enriched functional networks were evaluated for each cell type. Principal component analyses were used to assess variability in responses. A random K-nearest neighbor - feature selection algorithm was used to identify markers predictive of sepsis severity, which were then validated in an independent data set. RESULTS: Neutrophils demonstrated the most distinct response to plasma from septic patients with 709 genes showing altered expression profiles, many of which are involved in established immunologic pathways. The amplitude of the neutrophil transcriptomic response was shown to be correlated with sepsis severity in two independent sets of patients comprised of 64 total septic patients. A subset of 30 transcripts selected using one set of patients was demonstrated to have a high degree of accuracy (82-90%) in predicting sepsis severity and outcomes in the other independent set. This subset included several genes previously established in sepsis pathogenesis as well as novel genes. CONCLUSIONS: These results demonstrate both the suitability and potential clinical relevance of a neutrophil reporter assay for studying plasma, in this case from septic patients. The distinctive transcriptional signature we found could potentially help predict severity of disease and guide treatment. Our findings also shed new light on mechanisms of immune dysregulation in sepsis.

OBJECTIVE: Women with endometriosis often need in vitro fertilization (IVF) to conceive. There are conflicting data on the results of IVF in patients with endometriosis. The present study was undertaken to investigate whether or not the stage of endometriosis affects the IVF outcome in order to give the best patient counseling MATERIALS AND METHODS: We compared IVF outcome measures between 40 patients with surgically confirmed minimal and mild endometriosis (American Society for Reproductive Medicine Stage I/II) and 38 patients with moderate and severe endometriosis (Stage III/IV). Each group was also compared with a control group of 157 patients with tubal factor infertility. Outcome measures included number of follicles, number of oocytes, mean number of ampoules of gonadotropins, cumulative pregnancy, and live birth rates RESULTS: Higher cancelation rates, higher total gonadotropin requirements, and lower oocyte yield were found in women with endometriosis Stage III and IV compared with both the Stage I/II and control groups. The fertilization rate was higher in Stage III/IV endometriosis compared to Stage I/II. Clinical pregnancy and live birth rates were comparable between patients with endometriosis Stage I/II and control group, whereas they were significantly lower in patients with endometriosis Stage III/IV compared to other two groups. CONCLUSION: The American Society for Reproductive Medicine classification of endometriosis is useful in predicting IVF outcome. Advanced endometriosis means a worse prognosis for IVF treatment compared to milder stages or tubal factor infertility. The decreased fertilization rate in Stage I/II endometriosis might be a cause of subfertility in these women, as a result of a hostile environment caused by the disease.

Summary Background Superficial fungal infections ( SFI ), one of the most prevalent diseases in the world, are infections of keratin‐rich structures of human body mostly caused by dermatophytes and yeasts. Objectives The goal of this study was to determine the possible changes in the epidemiology of SFI on the territory of Southeastern Serbia and to investigate epidemiological characteristics and the influence of SFI on the patient's quality of life. Methods From 2012 to the end of 2017, samples of 1643 patients (568 males and 1075 females, mean age 40.32 ± 22.44 years) with suspected SFI from Southeastern Serbia were examined using the standard mycological methods. The questionnaires were used to investigate epidemiological characteristics. Results Superficial fungal infections were diagnosed in 20.5% (n = 336) of patients. In the group of dermatophytes, the most prevalent was Microsporum canis (63.9%, n = 76) followed by Trichophyton mentagrophytes (21.8%, n = 26). Non‐ albicans Candida species were dominant aetiological agents of superficial candidosis (62.3%). BMI ≥25 kg/m 2 ( P = 0.019) was determined as an independent risk factor for SFI . There was a statistically significant difference in the EQVAS score between the groups of patients and the control group ( P &lt; 0.001). Conclusions Results of conducted study indicate that SFI prevalence has not changed in the previous period. However, increase of Candida ‐ SFI prevalence, especially Candida onychomycosis, was established.

In the last 30 years the development of artificial intelligence (AI) that can be applied in all areas of science has brought numerous benefits. Many researchers have explored potential applications of intelligent techniques in every field of medicine. The importance of AI is reflected in the possibility of proper decision-making, without subjectivity, fatigue, with unlimited possibilities of remembering and making conclusions. This is important in medicine, for the prevention and diagnosis of various diseases, as well as therapy monitoring. Numerous studies have shown that AI will soon replace medical staff in numerous activities, as results obtained by AI are better and more precise. A number of applications have been developed to simplify patient adherence to therapy, which ultimately affect the therapy. The application of AI is present in the pharmaceutical industry, in the design of new drugs. This precludes preclinical tests, which are extremely long and expensive. AI makes conclusions based on the available data, so the validity of data must be taken into account because extremely important algorithms are based on them. An important aspect is the protection of patient data since the possibility of data becoming public is a major ethical problem. Computers and AI are the cause why many people are replaced at their jobs, and the tendency is that such a trend continues. The question arises whether the machines should replace people in areas such as medicine, where feelings, empathy, and warmth are very important factors.

This prospective study was conducted with the aim of examining the efficacy of lowering dialysate calcium (dCa) in order to: (i) stimulate bone turnover in hemodialysis patients with biochemical signs of adynamic bone disease (ABD) (hypercalcemia, normal alkaline phosphatase and intact parathyroid hormone (iPTH) <150 pg/mL); and (ii) diminish hypercalcemia in patients with secondary hyperparathyroidism (sHPT) (hypercalcemia, high alkaline phosphatase and iPTH > 400 pg/mL), thus permitting the use of calcium-containing phosphorus binders and vitamin D metabolites. Patients were divided into: an ABD-treated group (24 patients), a sHPT-treated group (18 patients), an ABD-control group (12 patients) and a sHPT-control group (11 patients). For the ABD- and sHPT-treated patients, hemodialysis was conducted with dCa 1.5 mmol/L for three months and then with dCa 1.25 mmol/L for an additional three months, while in the control groups hemodialysis was conducted with dCa 1.75 mmol/L during the entire study. Reduction of dCa in patients with ABD caused a slight but insignificant decrease of Ca, but a significant and permanent increase of bone-specific alkaline phosphatase and intact parathyroid hormone level serum levels. Reduction of dCa in patients with sHPT slightly but insignificantly decreased Ca and intact parathyroid hormone level values. Nevertheless, this enabled the calcium-based phosphate binder dose to be raised and vitamin D3 metabolites to be introduced. Logistic regression analysis indicated that milder bone disease (both ABD and sHPT) was associated with more the favorable effect of dCa reduction. Thus, low dCa stimulated parathyroid glands and increased bone turnover in ABD patients, and enabled better control of mineral metabolism in sHPT patients.

BACKGROUND: Distal renal tubular acidosis (dRTA), due to impaired acid secretion in the urine, can lead to severe long-term consequences. Standard of care (SoC) oral alkalizers, requiring several daily intakes, are currently used to restore normal plasma bicarbonate levels. A new prolonged-release formulation, ADV7103, has been developed to achieve a sustained effect with an improved dosing scheme. METHODS: In a multicenter, open-label, non-inferiority trial (n = 37), patients with dRTA were switched from SoC to ADV7103. Mean plasma bicarbonate values and proportion of responders during steady state therapy with both treatments were compared, as were other blood and urine parameters, as well as acceptability, tolerability, and safety. RESULTS: When switching from SoC to ADV7103, the number of daily intakes was reduced from a median of three to twice daily. Mean plasma bicarbonate was increased and non-inferiority of ADV7103 was demonstrated (p < 0.0001, per protocol), as was statistical superiority (p = 0.0008, intention to treat [ITT]), and the response rate increased from 43 to 90% with ADV7103 (p < 0.001, ITT). Urine calcium/citrate ratio was reduced below the threshold for risk of lithogenesis with ADV7103 in 56% of previously non-responders with SoC (p = 0.021, ITT). Palatability was improved (difference [95% CI] of 25 [10.7, 39.2] mm) and gastrointestinal discomfort was reduced (difference [95% CI] of - 14.2 [- 25.9, - 2.6] mm) with ADV7103. CONCLUSIONS: Plasma bicarbonate levels and response rate were significantly higher with ADV7103 than with SoC. Urine calcium/citrate ratio, palatability, and gastrointestinal safety were significantly improved, supporting the use of ADV7103 as first-line treatment for dRTA. TRIAL REGISTRATION: Registered as EudraCT 2013-002988-25 on the 1st July 2013 Graphical abstract.