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The cytochrome P450 superfamily consists of hemeproteins involved in the detoxication of different xenobiotics, including drugs. The CYP2 gene family is responsible for the metabolism of 80% of the drugs in clinical use. There are considerable interindividual and interethnic variabilities in the rate of drug metabolism as a result of genetic polymorphisms. The goal of our study was to determine the frequency of 10 genetic polymorphisms in CYP2 family genes to give light on the pharmacogenetic defects of the main CYPs, involved in drug metabolism, in Bulgarian individuals. We detected high allele frequency for CYP2D6*10 (0.27), CYP2D6*4 (0.22), and CYP2B6*9 (0.24), followed by CYP2C19*2 (0.14), CYP2C9*3 (0.11) and CYP2C9*2 (0.09). The genotype frequencies were also determined for all investigated variants. In total 47.2% of the analyzed individuals carried CYP2D6 genetic polymorphisms – 5.6% carried a single variant and 41.6% were found to have two or more such variants. Homozygotes for CYP2D6 variants were established among 14% of Bulgarian individuals. Determination of the prevailing pharmacogenetic polymorphisms of the CYPs, most responsible for drug metabolism, will lead to a lower risk of drug toxicity, increased drug efficacy, and drug dose optimization.

Congenital heart abnormalities are rare and most often occur separately. These structural and functional disorders can cause a range of diseases that vary in severity, from mild or even asymptomatic to severe and life-threatening. Occasionally these conditions could cause no symptoms in which case they are found accidentally when the patient is examined for other reasons or during autopsy. In this article we present the case of a 47-year-old male patient with triple congenital heart anomaly detected in two consecutive tests performed in pre-hospital medical care.

Presents the main design issues of a distance learning course on Business on the Internet. The instructional design is based on a learner-centered strategy which allows learners to construct their own knowledge while solving real business problems and transferring their knowledge to other learners. (AEF)

The paper considers a method for optimization of piezoelectric voltage of vibrating microelectromechanical energy harvester with respect to the output voltage. The investigated vibrating elements are cantilevers and doubly clamped beams with piezoelectric thin film layers. Interdigitated electrodes are disposed on the top surface of piezoelectric layers in order to increase the efficiency of the energy harvester. The non-uniform distribution of piezoelectric charges along vibrating structure is a result of non-uniform distribution of bending stress. The aim of optimization method described in the paper is to determine the optimal length and position of the piezoelectric interdigitated electrodes on the surface of the elastic beam so that the maximum output voltage to be obtained at minimal possible lengths of the piezoelectric layers. The considered optimization method can be used for design of hybrid piezoelectric energy harvesters with combined vibrating and triboelectric action. [ABSTRACT FROM AUTHOR]

Temperature dependences of the heat capacity of cobalt manganites NdM CoMnO (M = Li, Na, and K) are studied by means of dynamic calorimetry in the range of 298.15−673 K. It is found that λ-shaped effects are observed on the C ~ f ( T) curve of cobalt manganites, due probably to second order phase transitions. Based on the experimental data, equations for the temperature dependences of the heat capacity of cobalt manganite are derived with allowance for the temperatures of phase transitions. The values of thermodynamic functions Н°( T)- Н°(298.15), S°( T), and Ф( T) are calculated. [ABSTRACT FROM AUTHOR]

Data about coffee consumed world-wide are somewhat contradictory. A conservative estimate, suggests a number of around 8 mln tones per year . Its production involves a comparable amount of by-products, mainly pulp, husks, skins and spent coffee grounds. Thus, a sustainable coffee industry requires the development of methods for utilization of coffee by-products. Among these, the preparation of renewable fuel additives (e.g. biodiesel) and carbon adsorbents is a promising alternative to the eventual dumping of biogenic substances, harmful to the environment. Extraction of coffee by-products is the first step towards their utilization. This work presents results on laboratory extraction of spent coffee grounds (SCG) with different solvents, discussed in the context of the preparation of renewable fuel additives. The aim of the present study is to develop a procedure for extraction of coffee residues, suitable for production of biofuels and adsorbents. [ABSTRACT FROM AUTHOR]

Metallic (Cu, Cn) and intermetallic (Cu-Sn) nanoparticles have been synthesized through a chemical reduction in water solution of corresponding chloride salts with NaBH4 as a reducing agent at room temperature and atmospheric pressure. Cu and Cu-Sn nanoparticles have been also prepared by a template technique in the pores of carbon foam (C-foam) used as a support. Solutions of CuCl2.2H2O and SnCl2.2H2O salts with different concentrations have been used for the Cu and Sn nanoparticles syntheses, while for the Cu-Sn nanoparticles synthesis salt solution mixtures with a different mass ratio of Cu: Sn (60:40, 50:50, 40:60) have been used. A commercial carbon foam (C-foam) preliminarily modified with the precursor salt solutions has been used as a support. These obtained nanoparticles, including those by the template technique have been investigated by electron microscopy. The SEM images have shown the existence of particles regular and also irregular by shape. The carried out IR spectroscopy analysis has given information about the nanopatricle surface state and chemical bonds created in the atom groups formed on their surface. [ABSTRACT FROM AUTHOR]

PURPOSE: Gamma-aminobutyric acid (GABA) is the principal inhibitory neurotransmitter, which is widely distributed throughout the mammalian brain including hypothalamus. Immunohistochemical research have reported GABA-ergic neurons and GABAA-receptors on the neurons of the preoptic area of anterior hypothalamus (PO/AH). The aim of this study was to investigate the influence of GABAA-ergic substances on thermoregulation in rats. METHODS: We have studied the effects of GABAA-active agents, muscimol and diazepam on core body temperature in rats after systemic administration (intraperitoneally, i.p.). Body temperature was measured with thermistor probes (TX8) and monitored on multichannel recorder THERMEX 16. RESULTS: Intraperitoneal injection of muscimol or diazepam has produced dose-dependent hypothermia. Hypothermic effect of muscimol was inhibited by pretreatment of bicuculline, a competitive antagonist of GABAA-receptors. Diazepam induced hypothermia was antagonized by pretreatment of animals with flumazenil, a competitive antagonist of benzodiazepine receptors. CONCLUSION: Hypothermia induced by muscimol or diazepam suggest involvement of GABAA receptors in the processes of thermoregulation. [ABSTRACT FROM AUTHOR]

Maintaining a body temperature within a narrow range is vital for the survival of all mammals, including humans. With the help of optogenetics, a better understanding of the thermoregulatory organs and pathways is achieved. Optogenetic activation of the GABAergic neurons in the ventral part of the lateral preoptic nucleus (VLPO) leads to decrease in the body temperature. On the other hand, number of drugs could alter the thermoregulatory balance, leading to a hyperthermic state, such as serotonin syndrome (SS). SS is a potentially life-threatening clinical condition that occurs as a result of a drug-induced increase in the intrasynaptic serotonin (5-hydroxytryptamine, 5-HT) levels due to overdose of a single drug or due to interaction between two or more drugs with serotonergic mechanism of action. In this hypothesis, we propose a novel method for the treatment of hyperthermia, a core clinical sign of serotonin syndrome, through deep brain stimulation (DBS). An electrode is stereotactically placed in the VLPO, which may lead to reduction of the core body temperature. If proven effective, this technique should be left as a salvage method for reduction of hyperthermia, where the drug treatment is insufficient or ineffective. This technique could be used for the treatment of other syndromes, where hyperthermia takes a central place, including malignant hyperthermia, neuroleptic malignant syndrome, etc. DBS, on the other hand, could be used alone to induce hyperthermia in patients with malignant diseases. Hyperthermia improves the immune response, improves the drug penetration and stop the repair of already damaged tumor cells after chemotherapy or radiotherapy. [ABSTRACT FROM AUTHOR]

Background: Probiotics have been used to prevent antibiotic-associated diarrhea (AAD), but practical guidelines are sparse. This trial evaluated the efficacy and safety of a high-dose, multistrain probiotic mix (Sinquanon), specially designed for prevention of AAD in adults., Methods: A phase IV, multicenter, randomized, double-blind, placebo-controlled, parallel-group clinical trial was conducted over 5 months. Participants receiving broad-spectrum antibiotics were administered the specialized probiotic mix or placebo from the first dose of antibiotics until 14 days after the last antibiotic dose. The primary outcome measure was the incidence of AAD., Results: In total, 564 participants were randomized (probiotic mix: 285; placebo: 279), of which 9 participants discontinued the trial early (probiotic mix: 3; placebo: 6), had no efficacy data, and were excluded from the efficacy analysis. The 555 remaining participants completed the trial and were included in the efficacy analysis (probiotic mix: 282; placebo: 273). AAD occurred less frequently in the studied probiotic mix versus placebo group (9.2% vs 25.3%, P < .001), resulting in an absolute risk reduction of 16% and a number needed to treat of 6 (95% confidence interval, 4.55-10.49). A significant improvement in the average gastrointestinal quality of life in the studied probiotic mix versus placebo group was also observed. There were no clinically relevant differences in the incidence of adverse events between the studied probiotic mix and the placebo group., Conclusions: The specially designed high-dose, multistrain probiotic mix (Sinquanon) demonstrated to be beneficial compared with placebo in the prevention of AAD in adults who received broad-spectrum antibiotics., Clinicaltrialsgov Identifier and Url: NCT05607056; https://classic.clinicaltrials.gov/ct2/show/NCT05607056., Competing Interests: Potential conflicts of interest. All authors have delivered scientific lectures on a given problem for various pharmaceutical companies, including Neopharm Bulgaria., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Introduction: The current understanding of the biological impacts of a static magnetic field (SMF) is restricted to the direct interactions of the magnetic field with biological membranes. The electrokinetic (zeta) potential is an electrochemical property of erythrocyte surfaces which was negatively charged in physiological media after SMF exposure (0.1‒2.0 T). Methods: The novel data about electrokinetic parameters of the erythrocytes is determined by microelectrophoresis after SMF-exposure in norm and heterozygous β-thalassemia. The methods of light scattering, lipid peroxidation, fluorescence microscopy are used. Results: The electrokinetic potential of erythrocytes in norm is increased after SMF intensities due to enhanced negatively exposed charges on the outer surface of the membrane accompanied by an increase in light scattering where changes in cell morphology are observed. Conversely, a decrease in the zeta potential of β-thalassemia erythrocytes upon SMF-treatment was determined because of the reduction in the surface electrical charge of the membranes, where a significant decrease in light scattering at 1.5 T and 2.0 T was recorded. Exposure to SMF (0.5-2.0 T) was associated with an increase in the malondialdehyde content in erythrocytes. Biophysical studies regarding the influence of SMF on the electrostatic free energy of cells shows an increase in negative values in healthy erythrocytes, which corresponds to the implementation of a spontaneous process. This is also the process in β-thalassemia cells after SMF exposure with lower negative values of free electrostatic energy than erythrocytes in norm. Discussion: The effect of static magnetic field (SMF 0.1-2.0 T) on the electrokinetic and morphological characteristics of erythrocytes in norm and β-thalassemia is determined and correlated with the increase/reduction in surface charge and shrinkage/swelling of the cells, respectively. Lipid peroxidation of healthy and β-thalassemia erythrocytes caused an enhancement of lipid peroxidation because of the higher concentrations of TBARS products in cellular suspension. SMF (0.1‒2.0 T) altered the spontaneous chemical processes with negative values of electrostatic free energy of erythrocytes in norm and β-thalassemia accompanied by a lower FITC-Concanavalin A binding affinity to membrane receptors (SMF 2.0 T). The electrokinetic properties of human erythrocytes in norm and β-thalassemia upon SMF treatment and their interrelationship with the structural-functional state of the membrane were reported. The presented work would have future fundamental applications in biomedicine., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Doltchinkova, Lozanova, Rukova, Nikolov, Ivanova and Roumenin.)

Vitamin D plays a role in regulating immune homeostasis, inflammation and has an impact on the pathogenesis of inflammatory bowel diseases (IBD). IBD has a multifactorial pathogenesis primarily associated with immune dysregulation, dysbiosis, structurally altered intestinal mucosa, and genetic factors. The immunomodulatory function of this vitamin is linked to its control over innate and adaptive immunity, facilitated through its nuclear vitamin D receptor, leading to the inhibition of nuclear factor kappa-B. This study aimed to investigate serum vitamin D levels in patients with IBD compared to healthy individuals and to evaluate the relationship between vitamin D and inflammatory markers. Cross-sectional study. The study included 106 participants divided into 2 groups: patients with IBD (92), and healthy controls (14). The diagnosis of IBD was based on clinical, laboratory, fecal, endoscopic, and histological findings, following the European guidelines for diagnosis and follow-up ECCO-ESGAR guidelines for diagnostic assessment of IBD from 2019. Serum vitamin D levels were measured along with laboratory tests, imaging, and endoscopic examinations. IBD activity was evaluated using the Montreal classification and clinical and endoscopic indices. Data analysis involved calculating the mean, minimum, and maximum values, standard deviation, and Pearson coefficient. The level of statistical significance for this study was set at P < .05. The study found a prevalence of vitamin D deficiency in 32.6% of patients with IBD, while 66.3% had insufficiency, as compared with healthy individuals. The mean levels of vitamin D in UC and CD were 16 ± 8.6 ng/mL, whereas in the control healthy group, they were 26 ± 9.73 ng/mL. A statistically significant reverse correlation was observed between lower vitamin D levels and higher levels of the inflammatory markers. The study concluded that IBD patients exhibit lower levels of vitamin D, which is associated with inflammation and may contribute to the pathogenesis of the disease., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2023 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background and Aims: We investigated the effect of WAY-163909, a novel 5-hydroxytryptamine selective 2C receptor agonist on body weight, blood glucose levels, and insulin resistance in obese and diabetic Wistar rats., Materials and Methods: We used twenty male Wistar rats with obesity and obesity-induced diabetes and twenty healthy Wistar rats as a control group. Each of these groups was separated into two subgroups: one with a daily intraperitoneal application of WAY-163909 (1 mg/kg) and one without. During the study, body weight, blood glucose levels, and immunoreactive insulin were tracked., Results: A reduction of 5.5% ( p < 0.05) in body weight was registered in the rat group with diabetes and obesity and 2.56% in the control group with a daily application of WAY-163909 (1 mg/kg) at the end of the study. Decreases of 35.4% in blood glucose levels at week four in the diabetic and obese rat group with a daily application of WAY-163909 (1 mg/kg) were registered. A reduction of insulin levels of 4.1% ( p < 0.05) in the diabetic and obese rats group using WAY-163909 was also observed., Conclusion: In our study, using WAY-163909 (1 mg/kg) led to a reduction of blood glucose levels, immunoreactive insulin, and body weight.

Pooled Immunoglobulin G (IgG), hematin and the membrane-disruptive amphipathic peptide melittin have received attention as powerful biomacromolecules for biomedical and pharmacology applications. Their action on surface properties, oxidation status and epifluorescence properties measured in vitro provide useful information about the functional activity of upper biomacromolecules in erythrocytes in vivo. The hemolysis of erythrocyte membranes, as well as changes in hematocrit and the morphology of erythrocytes, was investigated here via fluorescence microscopy using FITC-concanavalin A binding to cells. The effect of melittin on the membrane capacitance and resistance of model lipid bilayers was probed via electrochemical impedance spectroscopy. Lipid bilayer capacitance was higher in the presence of 0.10 g/L melittin compared to that in the control, which is likely related to bilayer thinning and alterations of the dielectric permittivity of melittin-treated membranes. The biomolecule interactions with red blood cells were probed in physiological media in which the surface of erythrocyte membranes was negatively charged. Surface parameters of erythrocytes are reported upon IgG/hematin and IgG/melittin treatment. Pooled IgG in the presence of melittin, preincubated IgG/hematin preparations promoted a significant decrease in the electrokinetic potential of erythrocytes (Rh-positive). A malondialdehyde (MDA) assay revealed a high rate of lipid peroxidation in erythrocytes treated with IgG/hematin or IgG/melittin preparations. This finding might be a result of pooled IgG interactions with the hematin molecule and the subsequent conformational changes in the protein molecule altering the electrokinetic properties of the erythrocyte membrane related to the Rh group type of erythrocytes. The pooled IgG and hematin are reported to have important consequences for the biophysical understanding of the immunopathological mechanisms of inflammatory, autoimmune and antibody-mediated pathological processes.

This study evaluates some of the neuromodulatory mechanisms of the memory loss preventive effect of alpha-lipoic acid (ALA) in a scopolamine (Sco)-induced rat model of Alzheimer's disease (AD) type dementia. Our results confirmed that Sco administration induces significant memory impairment, worsens exploratory behaviour and habituation, increases acetylcholinesterase (AChE) activity, and induces pathological monoamine content changes in the prefrontal cortex and hippocampus. ALA administration largely prevented Sco-induced memory impairment. It also improved exploratory behaviour and preserved habituation, and it decreased AChE activity, reversing it to control group levels, and corrected aberrant monoamine levels in the prefrontal cortex and hippocampus. According to the data available, this is the first time that ALA-induced changes in AChE and monoamine levels in the prefrontal cortex and hippocampus (brain structures related to learning and memory) have been demonstrated in a Sco-induced rat model of AD type dementia., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Introduction: Colorectal cancer is the third most common cancer type worldwide. Fluoropyrimidines and their prodrug-based regimens are widely applied as primary medications. The main enzyme responsible for the rate-limiting step in pyrimidine and for the 5-fluorouracil catabolism is dihydropyrimidine dehydrogenase (DPD)., Aim: We aimed to screen DPD level and the changes of plasma antioxidant capacity of colorectal cancer patients on 5-fluorouracil regimen., Materials and Methods: Human DPD Elisa Kit based on sandwich enzyme-linked immune-sorbent assay and spectrophotometric methods (FRAP and ABTS) were used in the study., Results: No statistically significant changes in plasma scavenging activity according to the results obtained in the ABTS system have been observed after evaluating all patients and considering DPD concentration. A decrease of the ferric reducing ability of patients' plasma taken after the administered treatment was found. The increase of DPD level is accompanied by a decrease in the p values and therefore the statistical significance of the differences increases., Conclusions: Based on the aforementioned observations, it could be concluded that some aspects of plasma antioxidant capacity and individuals' antioxidant status might be involved in the pathogenesis of the disease and could be altered by the activity of some enzymes. The cancer therapy in question, by the specificity of its mechanism of action, can modify patient's oxidative status., (This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: MELD score and MELD score derivates are used to objectify and grade the risk of liver-related death in patients with liver cirrhosis. We recently proposed a new predictive model that combines serum creatinine levels and maximum liver function capacity (LiMAx®), namely the CreLiMAx risk score. In this validation study we have aimed to reproduce its diagnostic accuracy in patients with end-stage liver disease., Methods: Liver function of 113 patients with liver cirrhosis was prospectively investigated. Primary end-point of the study was liver-related death within 12 months of follow-up., Results: Alcoholic liver disease was the main cause of liver disease (n = 51; 45%). Within 12 months of follow-up 11 patients (9.7%) underwent liver transplantation and 17 (15.1%) died (13 deaths were related to liver disease, two not). Measures of diagnostic accuracy were comparable for MELD, MELD-Na and the CreLiMAx risk score as to power in predicting short and medium-term mortality risk in the overall cohort: AUROCS for liver related risk of death were for MELD [6 months 0.89 (95% CI 0.80-0.98) p < 0.001; 12 months 0.89 (95% CI 0.81-0.96) p < 0.001]; MELD-Na [6 months 0.93 (95% CI 0.85-1.00) p < 0.001 and 12 months 0.89 (95% CI 0.80-0.98) p < 0.001]; CPS 6 months 0.91 (95% CI 0.85-0.97) p < 0.01 and 12 months 0.88 (95% CI 0.80-0.96) p < 0.001] and CreLiMAx score [6 months 0.80 (95% CI 0.67-0.96) p < 0.01 and 12 months 0.79 (95% CI 0.64-0.94) p = 0.001]. In a subgroup analysis of patients with Child-Pugh Class B cirrhosis, the CreLiMAx risk score remained the only parameter significantly differing in non-survivors and survivors. Furthermore, in these patients the proposed score had a good predictive performance., Conclusion: The CreLiMAx risk score appears to be a competitive and valid tool for estimating not only short- but also medium-term survival of patients with end-stage liver disease. Particularly in patients with Child-Pugh Class B cirrhosis the new score showed a good ability to identify patients not at risk of death.

Leptin is an adipokine that regulates body weight by decreasing appetite and increasing energy expenditure. Besides the effects on food intake, leptin can regulate energy expenditure at least in part by modulating thermogenesis. Many of the effects of leptin are attributable to action in the central nervous system, particularly in the hypothalamus. Common forms of obesity are associated with increased leptin levels and a failure to suppress feeding and mediate weight loss in response to exogenous leptin. This apparent leptin ineffectiveness defines a state of so-called leptin resistance. We examined the effect of leptin on core body temperature in rats with normal weight and diet-induced obesity (DIO), as well as thermoregulatory interactions between leptin and GABA B -agonist and an antagonist. We found that leptin retains the ability to induce hyperthermic effect in rats with DIO. Additionally, temperature responses produced by GABA B agonist and antagonist are altered in a state of obesity and by administration of leptin. We evaluated whether the medial preoptic area of the anterior hypothalamus (MPA) still remains sensitive to leptin action during DIO. Using extracellular recordings of neurons and phospho-signal transducer and the activator of transcription 3 (pSTAT3) immunohistochemistry, we have provided strong evidence that leptin signaling in the MPA is impaired in obese rats. We believe that leptin resistance in the MPA may play a role in the pathogenesis of obesity and obesity-related disease states.

Natural killer (NK) cells can discriminate between normal and cancer cells and are known to directly recognize and kill malignant cells or induce apoptosis. Thus, activation of NK cells is considered as a promising strategy for cancer treatment. However, clinical application has been somewhat limited because of difficulties in the preparation of sufficient number of highly cytotoxic/activated NK cells in vitro . We used cytokine stimulation to provide a suitable environment (activating receptor-ligand interactions) for the expansion of NK cells. This method potently expanded NK cells, and the final product was composed of highly proliferating NK cells. The expanded NK cells showed significant upregulation of various activation receptors such as CD69 and NKG2D. The latter is a particularly important receptor for triggering NK cell responses toward tumor cells.

Background: MELD attempts to objectively predict the risk of mortality of patients with liver cirrhosis and is commonly used to prioritize organ allocation. Despite the usefulness of the MELD, updated metrics could further improve the accuracy of estimates of survival., Aims: To assess and compare the prognostic ability of an enzymatic 13 C-based liver function test (LiMAx) and distinct markers of liver function to predict 3-month mortality of patients with chronic liver failure., Methods: We prospectively investigated liver function of 268 chronic liver failure patients without hepatocellular carcinoma. Primary study endpoint was liver-related death within 3 months of follow-up. Prognostic values were calculated using Cox proportional hazards and logistic regression analysis., Results: The Cox proportional hazard model indicated that LiMAx (p < 0.001) and serum creatinine values (p < 0.001) were the significant parameters independently associated with the risk of liver failure-related death. Logistic regression analysis revealed LiMAx and serum creatinine to be independent predictors of mortality. Areas under the receiver-operating characteristic curves for MELD (0.86 [0.80-0.92]) and for a combined score of LiMAx and serum creatinine (0.83 [0.76-0.90]) were comparable., Conclusions: Apart from serum creatinine levels, enzymatic liver function measured by LiMAx was found to be an independent predictor of short-term mortality risk in patients with liver cirrhosis. A risk score combining both determinants allows reliable prediction of short-term prognosis considering actual organ function. Trial Registration Number (German Clinical Trials Register) # DRKS00000614.

Objective To identify the demographic patterns of mortality, the time spent before death in the emergency department (ED), and the causes of fatal outcomes. Methods We performed a 5-year (01/01/2011 to 01/01/2016) retrospective analysis of all non-traumatic deaths in the ED of the UMHAT - Pleven. To extract the necessary information, we used the registers in the ED until the patients' death. Results Among 156,848 patients in the study period, 381 died and the mortality rate was 2.4/100000. The male:female ratio was 1.48:1. The 71-80 years age group was the most affected. The mean (SD) age of patients who died in the ED was 69.9 ± 8.4 years. Most non-traumatic deaths (222 cases) were due to cardiovascular disease. Most patients (70.9%) died within 2.3 h after arrival. The factors contributing to mortality included poverty, transporting the patient to hospital too late, and a lack of developed care centres for terminally ill patients. Conclusion Most patients die within approximately 2 h after arrival at the ED. The main cause of death is acute myocardial infarction. Pulmonary embolism remains unrecognized in most patients (69%). Oncological pathology is among the main causes (7.4%) of mortality.

Brain structure is a fundamental determinant of brain function, both of which decline with age in the adult. Whereas short-term exercise improves brain size in older adults, the impact of endurance training on brain structure when initiated early and sustained throughout life, remains unknown. We tested the hypothesis that long-term competitive aerobic training enhances cortical and subcortical mass compared to middle to older-aged healthy adults who adhere to the minimum physical activity guidelines. Observations were made in 16 masters athletes (MA; 53 ± 6 years, VO2max = 55 ± 10 ml/kg/min, training > 15 years), and 16 active, healthy, and cognitively intact subjects (HA; 58 ± 9 years, VO2max = 38 ± 7 ml/kg/min). T1-weighted structural acquisition at 3T enabled quantification of cortical thickness and subcortical gray and white matter volumes. Cardiorespiratory fitness correlated strongly with whole-brain cortical thickness. Subcortical volumetric mass at the lateral ventricles, R hippocampus, R amygdala, and anterior cingulate cortex, correlated with age but not fitness. In a region-of-interest (ROI) group-based analysis, MA expressed greater cortical thickness in the medial prefrontal cortex, pre and postcentral gyri, and insula. There was no effect of group on the rate of age-related cortical or subcortical decline. The current data suggest that lifelong endurance training that produces high levels of cardiorespiratory fitness, builds cortical reserve early in life, and sustains this benefit over the 40-70 year age span. This reserve likely has important implications for neurological health later in life.

Objective: The authors describe a stimulus case that led training staff to examine and revise the supervision policy of the adult and child and adolescent psychiatry clinics. To inform the revisions, the authors reviewed the literature and national policies., Methods: The authors conducted a literature review in PubMed using the following criteria: Supervision, Residents, Training, Direct, and Indirect and a supplemental review in Academic Psychiatry. The authors reviewed institutional and Accreditation Council for Graduate Medical Education resident and fellow supervision policies to develop an outpatient and fellow supervision policy., Results: Research is limited in psychiatry with three experimental articles demonstrating positive impact of direct supervision and several suggesting different techniques for direct supervision. In other areas of medicine, direct supervision is associated with improved educational and patient outcomes. The authors present details of our new supervision policy including triggers for direct supervision., Conclusions: The term direct supervision is relatively new in psychiatry and medical education. There is little published on the extent of implementation of direct supervision and on its impact on the educational experience of psychiatry trainees and other medical specialties. Direct supervision has been associated with improved educational and patient outcomes in nonpsychiatric fields of medicine. More research is needed on the implementation of, indications for, and effects of direct supervision on trainee education and on patient outcomes.

The aim of the study was to evaluate the influence of dietary and demographic factors and some habits on the prevalence of Helicobacter pylori infection in 150 dyspeptic patients examined endoscopically and by the urea breath test. Positivity rate was lower (50.6%) in patients consuming honey ≥1 day weekly compared with the remainder (70.8%) and in those consuming green/black tea ≥1 day weekly (45.2%) compared with the other patients (64.8%). Logistic regression confirmed that the factors associated with significantly lower H. pylori positivity rate were the consumption of honey (odds ratio [OR], 0.38; 95% confidence interval [CI], 0.19-0.78) and green/black tea (OR, 0.45; 95% CI, 0.21-0.95). In conclusion, honey and green/black tea intake is associated with reduced prevalence of H. pylori infection., (Copyright © 2015 Elsevier Inc. All rights reserved.)

The aim of the retrospective study was to evaluate geographic regions and residence places as possible risk factors for primary Helicobacter pylori antibiotic resistance in Bulgaria. Data from Sofia region, exhibiting the highest living density, were compared to those from other residence places. In total, 588 H. pylori strains from untreated adults who filled a questionnaire were evaluated. Strain susceptibility was assessed by a breakpoint susceptibility test. Resistance rates to metronidazole and clarithromycin have been found to increase, and that to tetracycline has been found to decrease over years. Clarithromycin resistance was 1.7-fold higher in Sofia inhabitants (23.5 %) than elsewhere (13.8 %) and 4.7-fold higher than that in villages (5.0 %). Moreover, the clarithromycin resistance rate was 2.6-fold lower in northern region (8.2 %) than in southern region (21.7 %). On multivariate analysis, sex and residence place were independent predictors for metronidazole resistance. Men were at lower risk for metronidazole resistance compared with women [odds ratio (OR) 0.703; 95 % confidence interval (CI) 0.499-0.990]. Importantly, Sofia inhabitants were at higher risk for the resistance compared with those living elsewhere (OR 1.453; 95 % CI 1.009-2.093). In conclusion, living in Sofia was associated with a risk for antibiotic resistance in H. pylori-positive adults. Living density could be associated with H. pylori resistance rates.

Objective: Children with Pervasive Developmental Disorders (PDDs) have social interaction deficits, delayed communication, and repetitive behaviors as well as impairments in adaptive functioning. Many children actually show a decline in adaptive skills compared with age mates over time., Method: This 24-week, three-site, controlled clinical trial randomized 124 children (4 through 13 years of age) with PDDs and serious behavioral problems to medication alone (MED; n = 49; risperidone 0.5 to 3.5 mg/day; if ineffective, switch to aripiprazole was permitted) or a combination of medication plus parent training (PT) (COMB; n = 75). Parents of children in COMB received an average of 11.4 PT sessions. Standard scores and Age-Equivalent scores on Vineland Adaptive Behavior Scales were the outcome measures of primary interest., Results: Seventeen subjects did not have a post-randomization Vineland assessment. Thus, we used a mixed model with outcome conditioned on the baseline Vineland scores. Both groups showed improvement over the 24-week trial on all Vineland domains. Compared with MED, Vineland Socialization and Adaptive Composite Standard scores showed greater improvement in the COMB group (p = .01 and .05, and effect sizes = 0.35 and 0.22, respectively). On Age Equivalent scores, Socialization and Communication domains showed greater improvement in COMB versus MED (p = .03 and 0.05, and effect sizes = 0.33 and 0.14, respectively). Using logistic regression, children in the COMB group were twice as likely to make at least 6 months' gain (equal to the passage of time) in the Vineland Communication Age Equivalent score compared with MED (p = .02). After controlling for IQ, this difference was no longer significant., Conclusion: Reduction of serious maladaptive behavior promotes improvement in adaptive behavior. Medication plus PT shows modest additional benefit over medication alone. Clinical trial registration information-RUPP PI PDD: Drug and Behavioral Therapy for Children With Pervasive Developmental Disorders; http://www.clinicaltrials.gov; NCT00080145.