The experience with colorectal cancer screening in the Czech Republic: the detection at earlier stages and improved clinical outcomes.

OBJECTIVES: Colorectal cancer (CRC) remains a major health burden. Although screening is recommended and considered beneficial, further data on its positive effects are needed for worldwide implementation. STUDY DESIGN: The aim of our national multicentre prospective observational study was to reveal and document clinicopathological differences in CRC diagnosed by screening and presented by disease symptoms as well as assess the efficiency of the screening programme in the Czech Republic. METHODS: Between March 2013 and September 2015, a total of 265 patients were enrolled in 12 gastroenterology centres across the Czech Republic. Patients were divided into screening and symptomatic groups and compared for pathology status and clinical characteristics. Screening was defined as a primary screening colonoscopy or a colonoscopy after a positive faecal occult blood test in an average-risk population. RESULTS: The distribution of CRC stages was significantly (statistically and clinically) favourable in the screening group (predominance of stages 0, I and II) compared with the non-screening group (P < 0.001). The presence of distant and local metastases was significantly less frequent in the screening group than in the symptomatic group (P < 0.001). Patients in the screening group had a higher probability of radical surgery (R0) than those diagnosed based on symptoms (P < 0.001). Systemic palliative treatment was indicated in two patients in the screening group compared with 23 patients in the non-screening group (P = 0.018). CONCLUSION: CRC diagnosed by screening disclosed less advanced clinicopathological characteristics and results in patients with a higher probability of radical surgery (R0) than diagnoses established based on symptoms, with subsequent management differing accordingly between both groups. These results advocate the implementation of a suitable worldwide screening programme.

The Potassium Channel Kv1.5 Expression Alters During Experimental Autoimmune Encephalomyelitis.

Multiple sclerosis (MS) is a chronic, inflammatory, neurodegenerative disease with an autoimmune component. It was suggested that potassium channels, which are involved in crucial biological functions may have a role in different diseases, including MS and its animal model, experimental autoimmune encephalomyelitis (EAE). It was shown that voltage-gated potassium channels Kv1.5 are responsible for fine-tuning in the immune physiology and influence proliferation and differentiation in microglia and astrocytes. Here, we explored the cellular distribution of the Kv1.5 channel, together with its transcript and protein expression in the male rat spinal cord during different stages of EAE. Our results reveal a decrease of Kv1.5 transcript and protein level at the peak of disease, where massive infiltration of myeloid cells occurs, together with reactive astrogliosis and demyelination. Also, we revealed that the presence of this channel is not found in infiltrating macrophages/microglia during EAE. It is interesting to note that Kv1.5 channel is expressed only in resting microglia in the naïve animals. Predominant expression of Kv1.5 channel was found in the astrocytes in all experimental groups, while some vimentin+ cells, resembling macrophages, are devoid of Kv1.5 expression. Our results point to the possible link between Kv1.5 channel and the pathophysiological processes in EAE.

Chronic physical illnesses in patients with schizophrenia spectrum disorders are independently associated with higher rates of psychiatric rehospitalization; a cross-sectional study in Croatia.

BACKGROUND: Increased physical morbidity in patients with schizophrenia spectrum disorders (SSDs) is well documented. However, much less is known about the association between somatic comorbidities and psychosis treatment outcomes. SUBJECTS AND METHODS: This cross-sectional study, nested within the larger frame of a prospective cohort study, was done in 2016 at Psychiatric Hospital Sveti Ivan, Zagreb, Croatia. Data were collected on a consecutive sample of 301 patients diagnosed with schizophrenia spectrum disorders who achieved a stable therapeutic dosage. Key outcome was the number of psychiatric rehospitalizations since diagnosis of the primary psychiatric illness. Predictors were number of physical and psychiatric comorbidities. By robust regression, we controlled different clinical, sociodemographic, and lifestyle confounding factors. RESULTS: The number of chronic somatic comorbidities was statistically significantly associated with a larger number of psychiatric rehospitalizations, even after the adjustment for number of psychiatric comorbidities and large number of other clinical, sociodemographic, and lifestyle variables. CONCLUSIONS: Chronic somatic comorbidities are associated with higher rates of psychiatric rehospitalization independently of psychiatric comorbidities and other clinical, sociodemographic, and lifestyle factors. Therefore, to treat psychosis effectively, it may be necessary to treat chronic somatic comorbidities promptly and adequately. Chronic somatic comorbidities should be considered equally important as the SSD, and should be brought to the forefront of psychiatric treatment and research with the SSD as one entity. The integrative approach should be the imperative in clinical practice.

Genetic differentiation of Liparus glabrirostris (Curculionidae: Molytinae) populations from the fragmented habitats of the Alps and Carpathian Mountains.

Populations of Liparus glabrirostris (Curculionidae: Molytinae), a weevil inhabiting higher altitudes of Central Europe, were sampled from 24 localities in the Alps and Carpathian Mountains, and the geographical structuring of genetic variation was analyzed. Comparison of the concatenated mitochondrial cytochrome oxidase subunit I and subunit II sequences revealed consistent genetic divergence between the populations of L. glabrirostris from different mountain ranges. In phylogenetic analysis using maximum parsimony and median-joining networks, concatenated mitochondrial haplotypes from the Alps and Carpathians clustered as separate lineages, with high bootstrap support. Substantial genetic distances determined between the separated groups ranged from 2.6 to 3.0%, with divergence estimated to have initiated approximately 0.85-0.98 million years ago. The nuclear elongation factor 1α gene was additionally amplified and haplotype analysis showed very low evolutionary divergence (0.2%), with separate clustering as well. The observed divergence suggests that the populations have been isolated for a long time, as a consequence of environmental changes resulting in varying fragmentation of habitats in the Alps and Carpathians, interrupting genetic exchange events and altering the genetic structure of L. glabrirostris populations. On the other hand, comparison of morphological characteristics showed no differences to confirm genetically well differentiated groups of populations. A polymerase chain reaction and restriction fragment length polymorphism-based method was therefore developed to discriminate between the Alpine and Carpathian lineages.

First Report of Alder Yellows Phytoplasma Associated with Common Alder (Alnus glutinosa) in the Republic of Macedonia.

Alder yellows phytoplasma (AldYp) is classified as a member of the 16SrV-group of phytoplasmas and is closely related to Flavescence dorée (FD), a quarantined pathogen of economic importance affecting vineyards across Europe. AldYp is associated with common (Alnus glutinosa) and grey alder (A. incana), and has been reported in France, Italy, Germany, Austria, Switzerland, the Baltic region, Serbia, and Montenegro (1,2,4). For Macedonian vineyards, so far, neither infection of grapevine with 16SrV-group of phytoplasmas nor the presence of the main FD phytoplasma vector, Scaphoideus titanus, has been recorded. However, the presence of FD-related phytoplasma was detected in wild Clematis vitalba. In September and October 2013, leaves with petioles from A. glutinosa exhibiting leaf discoloration and yellowing were collected from two sites (41°23'43″ N, 22°54' E and 41°23' N, 22°53' E) in southeast Macedonia near the village of Smolare (Strumica district). Eight samples were collected from each site. Leaves of six asymptomatic alder seedlings collected from the same sites served as a control. Nucleic acids were extracted from fresh leaf midribs and petioles using a DNeasy Plant Mini Kit (Qiagen, Hilden, Germany). Initial phytoplasma identification was carried out by nested PCR assay of the 16S rRNA gene, using universal primers P1/P7 and R16F2n/R16R2 followed by RFLP with MseI endonuclease (Fermentas, Vilnius, Lithuania), as previously reported (4). Characterization of detected phytoplasmas was performed by amplifying two genetic loci specific for the members of the 16SrV group phytoplasmas; the ribosomal protein gene operon (rp) using primers rp(V)F1/rpR1 and rp(V)F1A/rp(V)R1A (3), and the non-ribosomal metionine aminopeptidase (map) gene using primer set FD9f5/MAPr1 and FD9f6/MAPr2 (1). The PCR amplicons were sequenced and deposited in NCBI GenBank database under the accession numbers KJ605448 to 52 (map) and KJ605453 to 57 (rp). The obtained sequences were compared with reference sequences of the 16SrV-group phytoplasmas (1,3) using the neighbor-joining method in MEGA5 (5). The presence of phytoplasma was detected in 14 of 16 symptomatic alder samples, while all control plants tested negative. The MseI restriction profiles were identical among all 14 samples and with the reference strains of the 16SrV group phytoplasmas (EY1 - 16SrV-A, FD-C - 16SrV-C, and FD-D - 16SrV-D). The rp-based phylogeny enabled identification of four diverse phytoplasma strains among the AldYp strains from Macedonia. Three strains clustered within the rpV-E subgroup while one belonged to rpV-L subgroup. Phylogenetic analysis of the more variable genetic locus, map, showed the presence of five diverse phytoplasma strains. Four strains belonged to the map-FD2 (FD-D, FD92) cluster, while one grouped within the map-FD1 (FD70) cluster. To our knowledge, this is the first report of 16SrV phytoplasma group occurrence on alder in Macedonia. The significant similarity between AldYp strains and FD sensu stricto indicate the risk of pathogen exchange between the wild ecosystem and the grapevine (1). Alder trees naturally infected with the FDp-related strains could therefore represent a serious risk for FD outbreak in Macedonian vineyards if local S. titanus populations developed. References: (1) G. Arnaud et al. Appl. Environ. Microbiol. 73:4001, 2007. (2) T. Cvrkovic et al. Plant Pathol. 57:773, 2008. (3) M. Martini et al. Int. J. Syst. Evol. Microbiol. 57:2037, 2007. (4) S. Radonjic et al. Plant Dis. 97:686, 2013. (5) K. Tamura et al. Mol. Biol. Evol. 28:2731, 2011.

Predicting depression with temperament and character in lung cancer patients.

Depression is highly prevalent in cancer patients. Variations in intensity and frequency of depression in cancer patients may be attributed, in part, to differences in personality dimensions. Our aim was to asses if dimensions of temperament and character could predict depression in lung cancer patients. Ninety newly diagnosed non-small cell lung cancer patients were assessed in the oncology unit with the Centre for Epidemiologic Studies Depression Scale (CES-D), pain subscale of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ) C30 and the Temperament and Character Inventory (TCI). Fifty out of 90 patients (55.6%) fulfilled the cut-off criteria for depression on the CES-D scale. Logistic regression performed to assess if depression was predicted by personality dimensions, revealed dimension of temperament Harm Avoidance and pain as significant predictors of depression. Depressive reactions are highly prevalent in lung cancer patients and related to patients' personality. These findings may be helpful in planning preventive, as well as psychoeducational and treatment programmes for newly diagnosed, and depression prone patients.

Validation of a patient satisfaction questionnaire in primary health care.

BACKGROUND: Improvement in patient satisfaction with healthcare services can be evaluated by satisfaction questionnaires of high construct validity. OBJECTIVES: To establish the dimensions and construct validity of a 20-item patient satisfaction questionnaire to assess satisfaction with general practice services. SUBJECTS: In total, 1314 adult patients of both genders, who were users of healthcare services at the General Medicine Department of Health Centre Valjevo in Serbia for two consecutive years, were included in the study. METHODS: Multidimensional scaling (MDS) was employed to identify similarities and dissimilarities among items comprising the satisfaction questionnaire. Patient satisfaction dimensions were estimated by principal component analysis for categorical data (CATAPCA). RESULTS: The MDS model configuration derived two dimensions: (1) patient satisfaction with the timeliness of healthcare service provision; and (2) patient centredness related to doctors' and nurses' commitment towards their health. In the CATAPCA model, two dimensions of patient satisfaction were found: the first dimension patient satisfaction with medical staff and the second dimension was indicative of contextual patient dissatisfaction. CONCLUSIONS: This study shows that the applied patient satisfaction questionnaire has high validity and reliability. It also has high sensitivity for longitudinal measurements, as well as good discriminatory power in measuring the different levels of patient satisfaction.

The first transendoscopic plastic to self-expandable metal stent replacement in Serbia and Montenegro using a diagnostic duodenoscope.

Studies have shown that SEMS remain patient longer with fewer associated complications compared with conventional plastic strents. Zilver stent, a nitinol zig-zag mash SEMS has a special advantage, having a thin introducer diameter of 7 Fr with a fully deployed span of 10mm. For a 48-year-old woman presented with obstructive jaundice and a diagnosis of unresectable pancreatic carcinoma with consequent stenosis of common bile duct (CBD), infiltration of local blood vessels and life expectancy longer than six months, it was decided that an endoscopic palliative drainage procedure should be performed. The technique of transendoscopic plastic to metal stent exchange is described, using a diagnostic duodenoscope. The patient lived 7 months after implementation of Zilver stent and died anicteric due to progression of a primary disease. The transendoscopic plastic to metal stent exchange is feasible palliative method which requires a basic endoscopic equipment and experienced staff and therefore is applicable in developing countries as well.

The effects of olanzapine and fluphenazine on plasma cortisol, prolactin and muscle rigidity in schizophrenic patients: a double blind study.

Pharmacotherapy of schizophrenia is associated with the stressful side effects. Muscle rigidity causes distress, discomfort and poor compliance. The aim of the study was to determine the relationship between plasma hormones (cortisol and prolactin/PRL) and muscle rigidity in female schizophrenic patients treated with olanzapine or fluphenazine. In a randomized, double-blind 22-weeks study, 12 patients were treated with olanzapine (5-20 mg/day) and 10 patients received fluphenazine (6-21 mg/day). Treatment with olanzapine moderately decreased, while treatment with fluphenazine significantly increased plasma cortisol levels and muscle rigidity. The marked and moderate increase in plasma PRL levels were found in patients treated with fluphenazine and olanzapine, respectively. The results suggested that olanzapine induced moderate neuroendocrine effects and a reduction in rigidity as compared to fluphenazine treatment.

Olanzapine in the treatment-resistant, combat-related PTSD--a series of case reports.

OBJECTIVE: Nightmares and insomnia in combat-related post-traumatic stress disorder (PTSD) might be resistant to treatment with selective serotonin reuptake inhibitors (SSRIs) and benzodiazepines. METHOD: We describe five case reports of patients suffering from long-lasting and intractable nightmares and insomnia. They were given different psychotropic agents in past few years, with no improvement in their sleep disturbance. Olanzapine was added to the current treatment regimen. RESULTS: Both nightmares and insomnia improved rapidly after olanzapine institution in all of five patients. No adverse events of olanzapine were reported. CONCLUSION: Olanzapine augmentation might be useful in alleviating treatment-resistant nightmares and insomnia in patients with combat-related PTSD.

Postcardiotomy assisted circulation with roller pump--early and late results.

The incidence of postcardiotomy myocardial failure (PMF) requiring mechanical circulatory support beyond IABP is reported to be 0.2% to 1.2%. From Dec. 1989 through Dec. 1995, 18 patients (0.3% of the total pump cases) were supported with roller pump type of LVAD. Assisted flow ranged from 3.5 up to 5 L/min with average support time of 35.5 hours. Six (33.3%) patients died while on LVAD. The causes of additional seven deaths (pts weaned of LVAD) were: myocardial failure (4), stroke (2) and intractable bleeding during removal of the LVAD (1). Overall, five patients (27.8%) were successfully discharged from the hospital. Two out of five long-term survivors died later, 6 months and 4 years postoperatively, both of cardiac causes. The actuarial survival rate of long-term survivors was 60% at 7 years, all of them being in NYHA functional class II. These results have proved efficiency of roller pump driven LVAD for short-term circulatory support in pts with PMF. Results are comparable to so far published data on postcardiotomy support with the same, as well as other types of more versatile and costly devices.

Gender differences in depression.

Depression is twice as common in women as in men, although some concern has been raised in terms of misdiagnosing depression in men. The incidence of depression in women varies during the life span. The peak incidence during childbearing years appears to be associated with cyclic hormonal changes. Women also present with reproductive -specific mood disorders: pre-menstrual dysphoric disorder (PMDD), depression in pregnancy, postpartal mood disorder (PDD) and perimenopausal depressive disorder. Gender differences were repeatedly observed in response to antidepressant medication. Premenopausal women appear to respond poorly and to show low tolerability to TCAs, but they tend to show greater responsiveness to the SSRIs. In contrast, men and postmenopausal women can respond equally to the TCAs and SSRIs. These differences are contributed to gender differences in pharmacokinetics of antidepressants and to the influence of menstrual cycle. These findings suggest the need for a gender-specific approach to the evaluation and management of depression.

Excess of allele1 for alpha3 subunit GABA receptor gene (GABRA3) in bipolar patients: a multicentric association study.

The available data from preclinical and pharmacological studies on the role of gamma amino butyric acid (GABA) support the hypothesis that a dysfunction in brain GABAergic system activity contributes to the vulnerability to bipolar affective disorders (BPAD). Moreover, the localization of the alpha3 subunit GABA receptor GABRA3 gene on the Xq28, a region of interest in certain forms of bipolar illness, suggests that GABRA3 may be a candidate gene in BPAD. In the present study, we tested the genetic contribution of the GABRA3 dinucleotide polymorphism in a European multicentric case-control sample, matched for sex and ethnogeographical origin. Allele and genotype (in females) frequencies were compared in 185 BPAD patients and 370 controls. A significant increase of genotype 1-1 was observed in BPAD females compared to controls (P=0.0004). Furthermore, when considering recessivity of allele 1 (females with genotype 1-1 and males carrying allele 1), results were even more significant (P= 0.00002). Our findings suggest that the GABRA3 polymorphism may confer susceptibility to or may be in linkage disequilibrium with another gene involved in the genetic etiology of BPAD.

[Combined use of internal mammary and right gastroepiploic arteries in myocardial revascularization with and without extracorporeal circulation]. / Kombinovana primena unutrasnje mamarne i desne gastroepiploicne arterije u revaskularizaciji miokarda sa i bez primene vantelesnog krvotoka.

Use of arterial grafts represent the new approach in coronary artery bypass grafting (CABG) surgery these days. This article represents our experience in use of two or more arterial grafts in combination (internal mammary artery--IMA and right gastroepiploic artery--RGEA). Between March 2000 February 2002, 10 patients underwent CABG with exclusive use of left or both IMAs and RGEA, with or without extracorporal circulation (ECC). In the group without ECC fast truck anesthesia was used. Post CABG catheterization was performed in three patients. There were no 30 day mortality or morbidity. Post CABG catheterization in two patients showed excellent graft patency. One patient continued to have chest pain and after the catheterization we found ostial narrowing of the celiac trunck which was successfully dilated. One of participants had abdominal hernia repair. Our opinion is that use of arterial grafts in CABG surgery has much lower risk, excellent patency and good long term prognosis.

Lack of association between GABRA3 and unipolar affective disorder: a multicentre study.

Available data on gamma amino butyric acid (GABA) support the hypothesis that a dysfunction in the brain GABAergic system activity contributes to vulnerability to affective disorders (AD), including bipolar disorder (BPAD) and unipolar disorder (UPAD). The localization of the alpha3 subunit GABA receptor (GABRA3) gene in Xq28, a region of interest for BPAD suggests that GABRA3 may be a relevant candidate gene. In the present study, we tested the genetic contribution of the GABRA3 dinucleotide polymorphism in a European multicentre UPAD case-control sample [UPAD (n = 106), controls (n = 212)]. Our negative results suggest that GABRA3 does not confer susceptibility nor is it in linkage disequilibrium with another close gene involved in the genetic aetiology of UPAD.

[Use of the internal thoracic artery in repeat myocardial revascularization surgery]. / Upotreba unutrasnje torakalne arterije u ponovnoj operaciji revaskularizacije miokarda.

The incidence of redo myocardial revascularization is increasing lately. These procedures are accompanied by the higher operative risk, and the use of internal thoracic artery graft may have additional negative impact on early-rization. Mortality and morbidity in this group did not differ significantly compared to a group where only venous grafts were used. Independent predictors of the unfavorable outcome (for both groups) were the presence of the chronic pulmonary disease, age over 65 and NYHA functional class IV. In the group with internal thoracic graft it was the age over 65, while in the group with only vein grafts it was chronic pulmonary disease. We have discussed potential problems during the redo procedure in patients in whom internal thoracic graft was used during the first procedure.

Platelet serotonin concentration in dialysis patients with somatic symptoms of depression.

Platelet serotonin (5-HT) concentration was measured in 65 male and 45 female chronic renal patients on hemodialysis (HD) with different somatic symptoms of depression (crying spells, irritability, sleep disturbance, fatigability, loss of appetite, weight loss, somatic preoccupation and loss of libido), to find out the relationship between the severity of symptoms and platelet 5-HT concentration. Male and female patients had significantly lower platelet 5-HT concentration than 62 male and 38 female healthy subjects. Gender-differences in platelet 5-HT values observed in healthy subjects were not found in patients. Platelet 5-HT concentration differed in the groups of patients with the different scores of particular somatic symptoms (loss of appetite and loss of libido), but was similar in patients with other somatic symptoms. There was no relationship between platelet 5-HT concentration and the severity of somatic symptoms, or between platelet 5-HT concentration and age of the patients. Gender-related differences in the occurrence of somatic symptoms were detected in patients with the different degrees of weight loss, somatic preoccupation and loss of libido. Our results suggest that platelet 5-HT concentration could not be used as a biological marker for the severity of somatic symptoms in chronic renal patients on HD.