Aim Triple-negative breast cancer (TNBC) is characterised by shorter overall survival and an early peak of distant recurrences with still no specific targeted treatment available. Vitamin D receptor (VDR) and insulin-like growth factor receptor 1 (IGFR) have recently been described as potential new targets for anticancer therapy, yet their roles in TNBCs are still to be explored. In this study we investigated VDR and IGFR expression in patients with TNBC and compared them with clinical and pathological parameters and survival to possibly demonstrate their prognostic and therapeutic relevance. Methods The study included 96 patients with TNBC. Clinical and pathological parameters were compared with the immunohistochemical expression of VDR and IGFR. Results Positive VDR immunostaining was present in 27% of tumours and inversely correlated with higher mitotic score, histological grade and higher proliferation index measured by Ki-67 and related to the increased overall survival (OS). Out of 96 patients with TNBC, 35.5% of tumours were IGFR positive and correlated with higher mitotic score and Ki-67, and strongly correlated with shorter disease-free survival (DFS). Patients with VDR-negative and IGF-positive tumours had significantly lower DFS and OS. Conclusion Approximately one third of TNBCs express VDR and/or IGFR. Their expression is linked with the recurrence of the disease and survival, which make them possible targets for treatment and a prognostic tool for dividing TNBCs into more homogeneous subgroups.

IntroductionThe addiction to heroin is a severe disorder and its treatment represents a complicated, long-lasting process, which includes a series of various interventions which have to be constantly adjusted to patients' present state and his abilities to accept the therapy. The addiction is very resistant to treatment and if the program is not at the same time, enough influential and persistent, but also acceptable to the addict to stick to it for months or even years, the expected results will not be achieved. Retention to the program, abstinence from the illicit drugs, reduction of illegal activities and improving the aspects of socially acceptable behaviour are the best indicators of therapeutic efforts [1-5].Already thirty years ago, the most of western-European countries and USA, Canada and Australia have accepted the use of methadone as a recognized method for treatment of opiate addicts and a useful tool in the frame of 'harm-reduction' approach for helping the not-motivated or incurable heroin addicts. Methadone enables those patients to stop or significantly reduce taking heroin. Although methadone does not create the feeling of euphoria similar to the effect of heroin, it replaces the biological lack of endorphins at the opioid receptors in brain and, with its help, the patient can achieve a psychophysical balance and control the pathological addict's craving. The use of methadone is the best way to attract the addicts from the street to the process of treatment and, if it is well organized and spread, can ultimately direct many addicts towards the programs that would help them in stabilizing the permanent abstinence [1-5].In the evaluation study carried out by the American National Institute for Drugs (NIDA) it has been found that the substitution therapy reduces users' heroin intake for 70%, and their criminal activity by 57 %. [6]. It has also been reported that the countries which use methadone attract up to 75% of opiate addicts to their programs, while those that do not use it, achieve less than 20 %, making the mortality of addicts due to overdose very high. A large number of addicts included in substitution programs function better socially, i.e. better fulfill their duties at the workplace and in families and display significantly less dealings with criminal activities, particularly with selling drugs, thus reducing the risk of initial drug abuse among the healthy population. Application of methadone improves the physical and mental health of the addict, his life gets longer and the risk for early sudden death is reduced. By using methadone, physical and mental health of addicts is improved, their lifespan prolonged i.e. the risk of sudden death is reduced. The addicts in substitution programs are less dangerous concerning the spread of HIV infection, hepatitis and encouraging others to take drugs. The use of methadone in pregnancy is absolutely indicated: it reduces the risk of unwanted pregnancy termination and the risk of damaging the fetus. [1]."Drug free" residential treatment of addictions in the frame of therapeutic communities (TZ) started in early sixties as groups of self and mutual help, as an alternative to the existing conventional programs. The mean duration of stay differs from TZ to TZ (18-60 months). The staff consists mostly of former addicts, while the rest of the staff consists of medical professionals from the field of mental health, psychologists, defectologists, and pedagogues and similar. The aim of staying in TZ is a global change of lifestyle, including abstinence from the illegal substances, elimination of anti-social activities, gathering skills for job-finding and the development of pro-social efforts and values. In TZ, detoxification is the condition to enter the treatment and not the goal of it. Most of the patients who enter TZ already have histories of multiple drug abuse, significantly disturbed psychosocial functioning and consequently, significantly lower quality of life. …

BACKGROUND The aim of the present study was to explore the differences in serum CRP, IL-6, TNF-α, ACTH and cortisol among patients with major depressive disorder with or without metabolic syndrome (MS) compared to a healthy control group. SUBJECTS AND METHODS The MDD study group consisted of 80 patients (mean age of 50.03±9.55 years). The control group was recruited from the hospital personnel and it consisted of 40 examinees (mean age of 47.20±7.99 years). All patients who participated in the study were diagnosed with depressive disorder using MINI questionnaire, and Hamilton rating scale for depression. Diagnosis of the metabolic syndrome was set by NCEP ATP III criteria. RESULTS Examinees with depression but without MS had significantly more cortisol concentration when compared to the control group. CRP was significantly higher in the MDD group when compared to the control group and in MDD+MS group when compared to the control group. IL6 serum levels were significantly higher in the MDD group when compared to the healthy control group, and in MDD+MS group when compared to the healthy control group. ACTH had significant independent predictive values for abdominal obesity. Levels of TNF-α were statistically significant independent predictors for hyperglycaemia. Statistically significant predictive values for MDD were found for cortisol, and IL-6. CONCLUSION Results shown here emphasise the importance of neuroendocrine and inflammatory factors in pathogenesis of depressive disorder and MS. Further prospective research is necessary to clarify possible causal relationship between depression and MS. It is necessary to investigate the possibility of a joint biological mechanism in pathogenesis of these two disorders with the special attention given to the disturbances in the immune system.

ACTIVITY OF THE HYPOTHALAMIC-PITUITARY-ADRENAL AXIS AND INFLAMMATORY MEDIATORS IN MAJOR DEPRESSIVE DISORDER WITH OR WITHOUT METABOLIC SYNDROME Marko Martinac, Dragan Babić, Milenko Bevanda, Ivan Vasilj, Danijela Bevanda Glibo, Dalibor Karlović & Miro Jakovljević Mostar Center for Mental Health, Mostar Health Center, Mostar, Bosnia and Herzegovina Clinical Department of Psychiatry, Mostar University Hospital, Mostar, Bosnia and Herzegovina Clinical Department of Internal Medicine, Mostar University Hospital, Mostar, Bosnia and Herzegovina Clinical Department of Psychiatry, Sestre Milosrdnice University Hospital Center, Zagreb, Croatia University of Mostar, School of Medicine, Mostar, Bosnia and Herzegovina Clinical Department of Psychiatry, University Hospital Center Zagreb, Zagreb, Croatia

BACKGROUND To explore correlation between clinical and endoscopic indices in inflammatory bowel disease (IBD) patients. SUBJECTS AND METHODS There were 112 patients with inflammatory bowel disease. All patients with diagnosed IBD was established a degree of clinical and endoscopic disease activity. CDAI (Crohn's disease activity index) was used as clinical and SES-CD (Simplified Endoscopic Crohn Disease Index) as endoscopic index for Crohn's disease. For ulcerative colitis Truelov & Witts index was used as clinical and Baron as endoscopic activity index. Correlation of clinical and endoscopic indices were compared in Crohn disease (CD) and ulcerative colitis (UC). Patients were analyzed by clinical entities - CD and UC, according to sex, age, parameters of anemia, duration of disease and education. RESULTS In the total of 112 IBD patients there were 69 patients diagnosed as ulcerative colitis (61.6%) and 43 as Crohn's disease (38.4%). There were 58 (51.8%) women and 54 (48.2%) men. Comparison between endoscopic and clinical indices in CD and UC demonstrated no significant differences in ilnness activity. Endoscopic and clinical disease activity was associated with a higher inflammatory parameters (CRP and leucocytes, L) and lower parameters of hemoglobin (Hb) and MCV. CONCLUSION Our research has established a good correlation between clinical and endoscopic index of disease activity in the CB and UC in inflammation. Clinical indices can be used for monitoring inflammation.

INTRODUCTION Use of intravenous heroin carries a risk of serious medical conditions, including acquiring blood-borne infections. Therefore, hepatitis B virus (HBV) and hepatitis C virus (HCV) infection represent a threat for people who inject drugs (PWID). The objectives of this study were to determine the extent and characteristics of risk factors for acquiring HBV and HCV infection in PWID included in opiate substitution treatment in the southern part of Bosnia and Herzegovina (B&H). METHODOLOGY The study included 120 adult PWID of both sexes who participated in opiate substitution treatment. All participants were interviewed, and their blood samples were tested for the presence of the surface hepatitis B virus antigen (HBsAg) and hepatitis C virus antibodies (anti-HCV). Prevalence data were obtained and compared to the serological status. RESULTS HBsAg prevalence among PWID was 0.8% (1/120), whereas seroprevalence of anti-HCV was 52.5% (63/120). PWID exposed to risk-behavior factors (such as unsafe sexual activity, serving prison sentence, and tattooing) were more frequently anti-HCV positive. Sharing drug paraphernalia was found to be the most significant risk factor. The highest predictive values for acquiring HCV-infection were attributed to PWID who used heroin for more than three years and who were unmarried. CONCLUSIONS HBsAg prevalence among PWID is rare (0.8%), while HCV-infection (52.5%) presents an important health and social issue among PWID in B&H. Sharing drug paraphernalia and intravenous heroin use longer than three years were the most prominent risk-behavior factors among the patients we investigated.

IntroductionMore severe mental illnesses, like depression, are connected with various cardiovasCular risk factors, like hypertension, obesity, atherogenic dyslipidemia, hyperglycemia, smoking and alcohol and other psychoactive substances abuse. Patients suffering from the depressive disorder display alterations of circadian rhythm, sleep disturbances, changes of autonomic nervous system, hypothalamus-hypophysis-adrenal gland axis (HHN) hyperactivity and changes of immunologic system. On the other hand, the somatic diseases, like obesity, hyperlipidemia, hypertension and diabetes mellitus type II are lately ever more often accepted as significant comorbid states in patients with more severe mental diseases. There is ever more data showing that the severe mental illnesses also affect the somatic health and only lately, these states are evaluated in the context of metabolic syndrome. Pathogenesis of metabolic syndrome, similar to pathogenesis of depression, is complex and insufficiently investigated. However, it is considered that the interactions of chronic stress, psychological trauma, hypercortisolism and disturbed immunologic functions contribute to the development of these disturbances [1-6].Metabolic syndrome (MS) is a complex multisystem disturbance, consisting of several components, namely: abdominal obesity, lipid metabolism dysfunction, hypertension and glucose metabolism dysfunction [7]. Besides that, the syndrome is connected with pro-inflammatory and pro-thrombotic state, resulting from the secretory activity of fat tissue, characterized by an increased level of inflammation mediators, endothelial dysfunction, hyperfibrinogenaemia, increased aggregation of thrombocytes, increased concentration of plasminogen activation inhibitors, increased levels of uric acid and microalbuminuria. MS represents the greatest risk for diabetes and cardiovascular diseases. MS was described in patients with polycystic ovaries syndrome, non-alcoholic steatosis of the liver, microalbuminuria and chronic renal failure [7-10].Depression is a complex disease, connected with alterations of sleep, appetite, body weight and level of physical activity, all of which can represent risk factors for the development of metabolic disturbances. In depressive patients, various physiological mechanisms can influence the development of metabolic syndrome, such as disturbed regulation of HHN axis and noradrenergic system, as well as various psycho-social factors, such as gender, age, smoking, stress levels, nutrition and level of physical activity [11-14]. It is possible that MS represents a connection between depression on one and KVB and diabetes on the other side. It is considered that chronic stress causes depression and consequently harmful lifestyle, which can lead to MS and consequently, development of KVB [15]. Disturbed regulation of HHN axis is typically connected to chronic stress and numerous studies had described such connection between depression and high levels of cortysole [16-18]. On the other hand, increased levels of cortysole are connected with components of metabolic syndrome, such as the abdominal obesity and glucose intolerance, so depression can indirectly influence the metabolism of glucose and the risk of diabetes development [19,20]. Besides that, psycho-social variables, such as depressive mood, can result in changes of levels of pro-inflammatory cytokines, which are also important components for the development of metabolic syndrome [21].Based on the research so far, we may say that the depressive patients show a greater incidence of cardiovascular diseases, hypertension and diabetes compared to the other psychiatric patients and the general population [22-39]. Symptoms of a depressive disturbance are frequently observed among the patients with MS and fatigue is a frequent symptom in states with a chronic activation of non-specific immunity, such as MS [3943].The aim of this study was to determine the psychosocial and clinical features of depressive patients diagnosed with MS. …

Since war activities, the previously mixed population of Mostar, Bosnia and Herzegovina, live in segregated parts of the town based on ethnicity. The aim of this study was to examine differences in health risks and health status between populations of the two parts of the town. Health status of 300 randomly selected primary care patients was evaluated by practicing family physicians in two main primary care centers in West and East Mostar. Each group consisted of 150 patients. Data were collected between December 2013 and May 2014. Patients were evaluated for smoking habit, alcohol consumption, body mass index, blood pressure and laboratory measurement of fasting glycemia. Family physicians provided diagnosis of chronic noninfectious diseases (hypertension, diabetes mellitus, cardiovascular disease, malignant disease, depression, and alcoholism). The two groups differed according to age, income, employment status, and rate of alcoholism and hypertension. Alcoholism (OR= 4.105; 95% CI 2.012-8.374) and hypertension (OR=1.972; 95% CI 1.253-3.976) were associated with inhabitants of West Mostar, adjusted for age, employment and income status on logistic regression. In conclusion, ethnic differences between inhabitants of the two parts of the town might influence health outcomes. These are preliminary data and additional studies with larger samples and more specific questions considering nutrition and cultural issues are needed to detect the potential differences between the groups.

Fifty-two-year-old man presented with back pain beginning a month before coming to a hospital. Patient lost five kilograms. Para-vertebral musculature of the lower back was tense, and percussion over the lumbar spine has provoked severe pain. Laboratory tests revealed a moderate anemia and severe thrombocytopenia (hemoglobin 87 g/L, platelets 31 x 109/L). Alkaline phosphatase and C-reactive protein were elevated (708 U/L and 134.3 mg/L; respectively).

INTRODUCTIONPsychoactive substances represent a problem dating from the fifties and starting to threaten the usual standards of life. People who get addicted to psychoactive substances become slaves of their problem and try to focus all their abilities towards providing a certain amount of psychoactive substance, weakening their integrity even further. The average age when the substance is taken for the first time is about 15 years, first injection happens about 21 (18 in the age group 18-24), while the time of the first addiction treatment ranges between 22-25 years of age.It is a rule that an addict takes more substances at the same time, usually starting with alcohol and marijuana and then quickly turning to opiates.1 Opiates include psychoactive substances of herbal origin, first of all opium, the dried milky juice from the not yet ripe fruits of white poppies, from which the morphine is later extracted. By means of twice-acetallizing the morphine, heroin (half-synthetic drug) is produced. This group also includes synthetic derivates of morphine, codeine and methadone, with similar effect.2 Addiction to heroin is in most cases very difficult to cure. So nowadays, it is usual to try to help the individuals and their families by means of replacing the expensive illegal psychoactive drug with narcotics heptanone (methadone) and buprenorphine. Patients receive these substances directly from their doctors.3 Methadone is widely used in treating the addiction throughout the world since 1960, while it was introduced to Croatia in 1990. The effects of methadone differ from the effects of other narcotics, because they last longer and there is no initial euphoria. The effect of methadone lasts up to 24 hours, thus enabling the patients to take it just once a day.4 The main effects of methadone are alleviating the craving, suppressing the withdrawal symptoms and blocking the euphoric effect of opiates. It is a paradox that the use of methadone has resulted in greater number of fatalities due to the drug overdose.5 Buprenorphine is used as a substitution therapy in treating the opiate addiction. It is used also as a substitution for methadone therapy if and when a patient decides to stop taking methadone. As opposed to methadone, buprenorphine may be given 3 times a week, enabling the users to have a better professional and social rehabilitation and generally, better quality of life. Higher doses of buprenorphine are better tolerated than high doses of methadone, seldom lead to the development of tolerance and is less addictive than methadone.6AnxietyAnxiety is a painful state of helplessness and vulnerability. It is a state of being tense, worried and expecting something terrible to happen. The feeling of anxiety, along with accompanying organic and physiological disturbances, or more precisely, with secretory and motoric discharge, overwhelms the person and in the most severe cases, represents an unbearable state and an incomparable experience.7 Anxiety is a constitutive part of life and we all feel it from time to time. We consider it a disease only when the anxiety is always present (general anxiety disorder), happening in particular situations which are usually not frightening, i.e. entering an elevator or taking a tram ride, leaving the house, social situations (phobias) or when it appears abruptly as an attack of particularly strong feeling of anxiety, called panic (panic disorder) and when that anxiety significantly limits the individual in achieving her/his personal, professional and other goals in life, thus reducing the quality of life. Not all anxiety should be feared, because it is common and informs the individual if he was in an alarming situation.8Anxiety is manifested with a variety of symptoms, such as heart thumping, sweating, tremor of hands and body, dry mouth, breathing difficulties, nausea, feeling warm or hot, muscle tension, feeling that we are unable to relax and feeling of having a globe in the throat. …

BACKGROUND A cross-sectional study in the Primary Care Medical Centre Mostar and Regional Medical Center "Safet Mujić" was conducted. Family physicians randomly surveyed, examined, and analyzed laboratory tests from 300 subjects divided into three age groups from 20-39, 40-54 and 55-65 years, totally 100 subjects. Data for age, sex, smoking status, alcohol consumption, body mass index, blood pressure, blood glucose, triglycerides and cholesterol, and the presence of chronic non-communicable diseases, including diagnosis of depression and the presence of stress were entered in medical records. RESULTS Levels of cholesterol were significantly higher in rural population as well as among students, and high triglyceride levels most frequently were presented in the student population. A group of farmers had a significantly higher prevalence of hypertension, DM and CVD compared to other investigated groups. The largest number of smokers and people who drink alcohol was present in group with the highest incomes, while obesity was significantly expressed in people with lower incomes. The group of examinees with the highest incomes had the greatest exposure to stress. CONCLUSIONS Socioeconomic processes have an impact on risk behavior of the adult population, and the presence of a number of chronic diseases that are accompanied with increased laboratory blood glucose, cholesterol and triglycerides levels.

AIM The main goal of this study was to compare the biochemical and histopathological findings in patients with sustained virological response (SVR) before and two years after the therapy with pegylated interferon α-2a and ribavirin in chronic hepatitis C. SUBJECTS AND METHODS The study was conducted at the Department of Internal Medicine and the Clinic for Infectious Diseases of the Clinical Hospital Mostar. The study included 48 patients whose treatment for chronic hepatitis C with pegylated interferon α-2a and ribavirin was finished two years prior to the achieved SVR at the end of the treatment. The main criterion for inclusion was a negative result of HCV RNA, determined by the RealTime HCV assay. After taking a history, physical examination, laboratory tests: AST, ALT, GGT, a liver biopsy were performed with the help of the ultrasound. The assessment of necroinflamatory score was determined by histologic activity index (HAI) score, and the stage of fibrosis according to Knodell's numerical score. RESULTS The values of AST and ALT levels were statistically significantly decreased after the successful treatment (p<0.001), as well as the value of HAI score (p=0.001) and the stage of fibrosis (p=0.010), in contrast to GGT (p=0.054). For the components of HAI score like focal necrosis (0.001) and portal inflammation (0.042) the result showed that they were significantly higher before the therapy, which was not true for the piecemeal (p=0.054) and confluated necrosis (p=0.078). The improvement of HAI score after therapy was found in 36 patients (75.0%), and 27 patients (56.2%) showed an improvement in the degree of fibrosis with the most common improvement of 1 degree (85.7%). One third of patients (31.3%) had the same result in the degree of fibrosis before and after the therapy. Before the treatment, a positive correlation was observed between ALT (p=0.039) and AST (p=0.04) with HAI, AST and the stage of fibrosis (p=0.04). In contrast, after the treatment the only correlation was observed between AST and the stage of fibrosis (p=0.042). CONCLUSION Virological and biochemical responses in patients with SVR may not reflect the histopathological effects of the treatment and therefore these patients should be monitored for the possible development of the liver cirrhosis and hepatocellular carcinoma.