Doctor of Philosophy

dissertationIn this work we focused on the electronic processes in active materials used in organic photovoltaics. Films of several electron donors, acceptors, and their blends were investigated by means of steady state optical and magnetic resonance probes. The efficiency of organic photovoltaics depends on film morphology, charge mobility and light absorption. Therefore we studied common donor materials with very different morphology: RR P3HT (regioregular poly(3-hexylthiophene)) and RRa P3HT (regio-random poly(3-hexylthiophene)). The charge transport is affected by regioregularity and molecular weight. Consequently, we examined RR P3HT polymers with various molecular weights. We learned that a polaron band at low photon energy only appears in the photoinduced absorption spectrum of low molecular weight RR P3HT. We studied two main approaches for improving the efficiency of organic photovoltaics: modifying the lowest (highest) unoccupied (occupied) molecular orbital, LUMO (HOMO) of the donor (acceptor) materials; as well as synthesizing polymer donors with low optical gap. TAES-V is a low-band gap polymer composed of three co-polymers having the structure of „donor-acceptor-donor?. Its record power conversion efficiency (~7%) when blended with PC70BM is partially due to the significantly red-shifted absorption. Our results show that an intrachain charge transfer exciton (CTE) is long-lived in this polymer and that it persists in the blend with PC70BM. In addition we studied three fullerene derivatives. The LUMO of a fullerene derivative can be changed by the addition of functional side groups to the fullerene cage that improves the organic solar cells performance. The addition can also lead to hindering of aggregation in the films, which consequently decreases the charge transport in solar cells. In the study of polymer/fullerene blends we mixed RR P3HT with three different fullerene derivatives. We conclude that higher power conversion efficiency of a blend is mainly due to the higher LUMO level and improved open circuit voltage. We also compared DOO-PPV (H-polymer) with DOO-PPV enriched with deuterium (D-polymer). We show that hyperfine interaction is weaker in the D-polymer and that the spin relaxation rate is four times smaller than in H-polymer. Consequently, the longer spin diffusion length makes the D-polymer better suited for higher performing organic spin-valves

Genetic association studies of symptoms, comorbidity and outcome in bipolar disorder and schizophrenia

Schizophrenia and bipolar disorder are complex brain disorders. Research has focused on applying brain research to understand the etiology, as well as clinical research to improve treatment, prognosis and progression. Schizophrenia and bipolar disorder are not lethal in and of themselves, but suicide and the presence of associated physical illnesses are of great concern, since these are the major causes of shortened life in afflicted individuals. In particular, the prevalence of type 2 diabetes and cardiovascular disease are twice as great in schizophrenia and bipolar disorder. By shifting the focus to underlying, sometimes comorbid causes, it is possible to increase knowledge of morbidity and mortality in cardiovascular disease, and thus improve the prognosis and progression for individuals with schizophrenia and bipolar disorder. Another interesting strategy for better understanding such complex disorders is to limit examination to symptoms in order to distinguish the genetics of the symptoms from the disorder itself. Genetic association studies are often used to investigate complex disease. The aim of this thesis was to investigate genetic associations between gene variants and metabolic risk factors in schizophrenia and bipolar disorder patients. An additional aim was to investigate known psychiatric risk genes in the dopamine system and their association to cognitive function. In Study I, D-amino acid oxidase activator gene (DAOA) and catechol-O-methyltransferase gene (COMT) were analyzed for allelic association to cognitive dysfunction in bipolar disorder patients. In Studies II-V, common metabolic risk gene variants were analyzed for allelic association to metabolic risk factors in schizophrenia and bipolar disorder patients, and to disorders per se. In Study VI, metabolic risk variants were analyzed for possible association to high-sensitive troponin T levels, which is a sensitive biomarker of cardiovascular damage in patients with acute coronary syndrome. In study I, single nucleotide polymorphisms in D-amino acid oxidase activator gene (DAOA) and catechol-O-methyltransferase gene (COMT) were associated to cognitive dysfunction in bipolar disorder patients. Data also suggest interaction between these genes. In studies II-V, single nucleotide polymorphisms in common metabolic risk genes: insulin-like growth factor II mRNA binding protein 2 (IGF2BP2), neurogenic locus notch homolog 2 (NOTCH2), thyroid adenoma associated (THADA), wolfram syndrome 1 (WFS1), purinergic receptor P2X, ligand-gated ion channel, 7 (P2RX7), and melatonin receptor 1B (MTNR1B) were associated with increased fasting plasma glucose in schizophrenia. Peroxisome proliferatoractivated receptor delta gene (PPARD) was associated with schizophrenia independent of glucose levels. Single nucleotide polymorphisms in common metabolic risk genes: calcium/calmodulin-dependent protein kinase kinase 2 (CAMKK2), melanoma inhibitory activity family, member 3 (MIA3), purinergic receptor P2X, ligand-gated ion channel, 7 gene (P2RX7), muscle RAS oncogene homolog gene (MRAS), SMAD family member 3 gene (SMAD3), peroxisome proliferator-activated receptor delta gene (PPARD), melatonin receptor 1B gene (MTNR1B), neurogenic locus notch homolog 2 gene (NOTCH2), HNF1 homeobox B gene (HNF1B) were associated with increased waist circumference in schizophrenia patients. Peroxisome proliferator-activated receptor delta gene (PPARD), melatonin receptor 1B gene (MTNR1B), neurogenic locus notch homolog 2 gene (NOTCH2), and homeobox B gene (HNF1B) were associated with schizophrenia irrespective of waist circumference. A genetic overlap between schizophrenia and bipolar disorder was identified through an association between melatonin receptor 1B gene (MTNR1B) and increased fasting plasma glucose also in bipolar disorder patients. Neurogenic locus notch homolog 2 gene (NOTCH2) was associated to bipolar disorder per se. In study VI, melatonin receptor 1B gene (MTNR1B) and neurogenic locus notch homolog 2 gene (NOTCH2) were associated with high-sensitive troponin T levels in schizophrenia women. Our genetic findings regarding D-amino acid oxidase activator gene (DAOA) and catecholO-methyltransferase gene (COMT) are in line with the dopamine hypothesis of cognitive function. Single nucleotide polymorphisms that increase metabolic risk in the general population are associated with elevated plasma glucose and increased waist circumference among schizophrenia and bipolar disorder patients, as well as with schizophrenia and bipolar disorder per se. The melatonin receptor 1B gene (MTNR1B) –dependent vulnerability for elevated fasting plasma glucose levels is evident in both schizophrenia and bipolar disorder. Neurogenic locus notch homolog 2 gene (NOTCH2) is associated to both to schizophrenia and bipolar disorder type 1 per se. These findings may reflect increased metabolic genetic vulnerability in schizophrenia and bipolar disorder patients, as well as common genetics between type 2 diabetes mellitus and these psychiatric disorders. In addition, in women with schizophrenia, there is a possible metabolic genetic component affecting high-sensitive troponin T levels, a biomarker for cardiovascular damage in individuals with acute coronary syndrome (chest pain)

COVID-19 in Northeast Bosnia and Herzegovina and patient’s length of hospitalization

BACKGROUND: Since the outbreak of COVID-19 pandemic, clinical data from various parts of the world have been reported. Up till now, there has been no clinical data with regards to COVID-19 from Bosnia and Herzegovina (B&H). The aim was to report on the first cohort of patients from B&H and to analyze factors that influence COVID-19 patient’s length of hospitalization (LOH). METHODS: This retrospective cohort study was conducted at Tuzla University Clinical Center (UKC), B&H. It involved 25 COVID-19 positive patients that needed hospitalisation between March 28th and April 27th 2020. The LOH was measured from the time of admission to discharge. Factors analyzed induced age, BMI, presence of known comorbidities, serum creatinine and O2 saturation upon admission. RESULTS: The mean age was 52.92 ± 19.15 years and BMI 28.80 ± 4.22. LOH for patients with BMI < 25 was 9 ± SE2.646 days (CI 95% 3.814–14.816) vs 14.182 ± SE .937 (CI 95% 12.346–16.018 p < 0.05; HR 5.148 CI95% 1.217 to 21.772 p = 0.026) for ≥25 BMI. The mean LOH of patients with normal levels of O2 ≥ 95% was 11.667 ± SE1.202 (CI95% 8.261 to 13.739; p = 0.046), while LOH for patients with < 95% was 14.625 ± SE 1.231 CI95% 12.184 to 16.757 p = 0.042; HR 3.732 CI95%1.137–12.251 p = 0.03). Patients without known comorbidities had a mean LOH of 11.700 ± SE1.075 (CI 95% 9.592–13.808), while those with comorbidities had a mean of 14.8 ± 1.303 (CI 95% 12.247–17.353; p = 0.029) with HR2.552. CONCLUSION: LOH varied among COVID-19 patients and was prolonged when analyzed for BMI ≥25, comorbidities, elevated creatinine, and O2 saturation < 95%. Furthermore, risk factors for COVID-19 patients in B&H do not deviate from those reported in other countries

The Importance of Serological Tests Implementation in Disseminated Candidiasis Diagnose

Candidiasis is defined as an infection or disease caused by a fungus of the genus Candida. Rate of disseminated candidiasis increases with the growth of the number of immunocompromised patients. In the the last few decades the incidence of disseminated candidiasis is in growth as well as the mortality rate. The aim of this survey is to show the importance of serological tests implemenation in disseminated candidiasis diagnose. This is a prospective study involving 60 patients with malign diseases with and without clinical signs of disseminated candidiasis and 30 healthy people who represent the control group. Apart from hemoculture, detection of circulating mannan antigen and adequate antibodies of Candida species applying comercial ELISA test was determined in each patient. This survey deals with relevant factors causing disseminated candidiasis. This survey showed that the group of patients with clinical signs of disseminated canididiasis had more patients with positive hemoculture to Candida species, then the group of patients without clinical signs of disseminated candidiasis. The number of patients being examined and positive to antigens and antibodies was higher (p<0.01) in the group of patients with clinical signs of disseminated candidiasis (7/30; 23.3%), then in the group of patients without clinical signs of disseminated candidiasis (0/30; 0%). Average value of titra antigen was statistically higher (p<0.001) in patients with Candida spp. positive hemocultures rather then in patients with Candida spp. negative hemocultures. In the group of patients with clinical signs of disseminated candidiasis 6/30 (20%) of patients had Candida spp.positive hemocultures while in the group of patients without clinical signs of disseminated candidiasis 1/30 (3.3%) of patients had Candida spp. positive hemocultures, which was considerably higher (p<0.05). Correlation of results of hemoculture and mannan antigens and antibodies in patients with disseminated candidiasis were statistically significant, while correlation of results of hemoculture and antibodies was insignificant. Because of low sensitivity of hemoculture and time needed for isolation of Candida spp., introducing serological tests in regular procedures would speed disseminated candidiasis diagnose

A Mumps Outbreak in Vojvodina, Serbia, in 2012 Underlines the Need for Additional Vaccination Opportunities for Young Adults

In 2012, mumps was introduced from Bosnia and Herzegovina to Vojvodina, causing an outbreak with 335 reported cases. The present manuscript analyses the epidemiological and laboratory characteristics of this outbreak, identifies its main causes and suggests potential future preventive measures. Sera of 133 patients were tested for mumps-specific antibodies by ELISA and 15 nose/throat swabs were investigated for mumps virus RNA by RT-PCR. IgG antibodies were found in 127 patients (95.5%). Mumps infection was laboratory-confirmed in 53 patients, including 44 IgM and 9 PCR positive cases. All other 282 cases were classified as epidemiologically-confirmed. More than half of the patients (n = 181, 54%) were 20-29 years old, followed by the 15-19 age bracket (n = 95, 28.4%). Twice as many males as females were affected (67% versus 33%). Disease complications were reported in 13 cases (3.9%), including 9 patients with orchitis and 4 with pancreatitis. According to medical records or anamnestic data, 190 patients (56.7%) were immunized with two doses and 35 (10.4%) with one dose of mumps-containing vaccine. The Serbian sequences corresponded to a minor genotype G variant detected during the 2011/2012 mumps outbreak in Bosnia and Herzegovina. Vaccine failures, the initial one-dose immunization policy and a vaccine shortage between 1999 and 2002 contributed to the outbreak. Additional vaccination opportunities should be offered to young adults during transition periods in their life trajectories

Characterization of Hemorrhagic Fever with Renal Syndrome Caused by Hantaviruses, Estonia

Thirty cases of hemorrhagic fever with renal syndrome (HFRS) due to Puumala virus (PUUV), Saaremaa virus (SAAV), and Dobrava virus infection were confirmed in Estonia. Except for the levels of serum creatinine, no remarkable differences were found in the clinical course of HFRS caused by PUUV and SAAV

SARS-CoV-2 virus outbreak and the emergency public health measures in Bosnia and Herzegovina: January – july 2020

Between March 5th and July 25th, 2020, the total number of SARS-CoV-2 confirmed cases in Bosnia and Herzegovina (BH) was 10,090, corresponding to a cumulative incidence rate of 285.7/100,000 population. Demographic and clinical information on all the cases along with exposure and contact information were collected using a standardized case report form. In suspected SARS-CoV-2 cases, respiratory specimens were collected and tested by real-time reverse-transcriptase polymerase chain reaction assay. The dynamic of the outbreak was summarized using epidemiolog

A five-year perspective on the situation of haemorrhagic fever with renal syndrome and status of the hantavirus reservoirs in Europe, 2005-2010

Hantavirus infections are reported from many countries in Europe and with highly variable annual case numbers. In 2010, more than 2,000 human cases were reported in Germany, and numbers above the baseline have also been registered in other European countries. Depending on the virus type human infections are characterised by mild to severe forms of haemorrhagic fever with renal syndrome. The member laboratories of the European Network for diagnostics of Imported Viral Diseases present here an overview of the progression of human cases in the period from 2005 to 2010. Further we provide an update on the available diagnostic methods and endemic regions in their countries, with an emphasis on occurring virus types and reservoirs

Phylogenetic pattern of SARS-CoV-2 from COVID-19 patients from Bosnia and Herzegovina: lessons learned to optimize future molecular and epidemiological approaches

This is the first report of molecular and epidemiology findings from Bosnia and Herzegovina related to ongoing severe acute respiratory syndrome coronavirus 2 epidemic. Whole genome sequence of four samples from coronavirus disease 2019 (COVID-19) outbreaks was done in two laboratories in Bosnia and Herzegovina (Veterinary Faculty Sarajevo and Alea Genetic Center). All four BiH sequences cluster mainly with European ones (Italy, Austria, France, Sweden, Cyprus, and England). The constructed phylogenetic tree indicates possible multiple independent introduction events. The data presented contribute to a better understanding of COVID-19 in the current reemergence of the disease

Interaction between COMT rs5993883 and second generation antipsychotics is linked to decreases in verbal cognition and cognitive control in bipolar disorder

Abstract Background Second generation antipsychotics (SGAs) are increasingly utilized in Bipolar Disorder (BD) but are potentially associated with cognitive side effects. Also linked to cognitive deficits associated with SGA-treatment are catechol-O-methyltransferase (COMT) gene variants. In this study, we examine the relationship between cognition in SGA use and COMT rs5993883 in cohort sample of subjects with BD. Methods Interactions between SGA-treatment and COMT rs5993883 genotype on cognition was tested using a battery of neuropsychological tests performed in cross-sectional study of 246 bipolar subjects. Results The mean age of our sample was 40.15 years and was comprised of 70 % female subjects. Significant demographic differences included gender, hospitalizations, benzodiazepine/antidepressant use and BD-type diagnosis. Linear regressions showed that the COMT rs5993883 GG genotype predicted lower verbal learning (p = 0.0006) and memory (p = 0.0026) scores, and lower scores on a cognitive control task (p = 0.004) in SGA-treated subjects. Interestingly, COMT GT- or TT-variants showed no intergroup cognitive differences. Further analysis revealed an interaction between SGA-COMT GG-genotype for verbal learning (p = 0.028), verbal memory (p = 0.026) and cognitive control (p = 0.0005). Conclusions This investigation contributes to previous work demonstrating links between cognition, SGA-treatment and COMT rs5993883 in BD subjects. Our analysis shows significant associations between cognitive domains such as verbal-cognition and cognitive control in SGA-treated subjects carrying the COMT rs5993883 GG-genotype. Prospective studies are needed to evaluate the clinical significance of these findings.http://deepblue.lib.umich.edu/bitstream/2027.42/134550/1/40359_2016_Article_118.pd