Genetic heritage of Croatians in the Southeastern European gene pool-Y chromosome analysis of the Croatian continental and Island population.

OBJECTIVES: The research objective of this study is to enlarge and deepen the Y chromosome research on the Croatian population and enable additional insights into the population diversity and historic events that shaped the current genetic landscape of Croatia and Southeastern Europe (SEE). MATERIALS AND METHODS: A high-resolution phylogenetic and phylogeographic analysis of 66 biallelic (SNPs) and 17 microsatellite (STRs) markers of the Y chromosome was performed using 720 Croatian samples. The obtained results were placed in a wider European context by comparison with ∼4450 samples from a number of other European populations. RESULTS: A high diversity of haplogroups was observed in the overall Croatian sample, and all typical European Y chromosome haplogroups with corresponding clinal patterns were observed. Three distinct genetic signals were identifiable in the Croatian paternal gene pool - I2a1b-M423, R1a1a1b1a*-M558, and E1b1b1a1b1a-V13 haplogroups. DISCUSSION: The analyses of the dominant and autochthonous I2a1b-M423 lineage (>30%) suggest that SEE had a significant role in the Upper Paleolithic, the R1a1a1b1a*-M558 lineage (19%) represents a signal from present day Slavic populations of Central Europe in the Croatian population, and the phylogeography of the E1b1b1a1b1a-V13 clade (around 9%) implies cultural diffusion of agriculture into Europe via the Balkan Peninsula. Am. J. Hum. Biol., 2016. © 2016 Wiley Periodicals, Inc. Am. J. Hum. Biol. 28:837-845, 2016. © 2016Wiley Periodicals, Inc.

Maternal genetic heritage of Southeastern Europe reveals a new Croatian isolate and a novel, local sub-branching in the x2 haplogroup.

High mtDNA variation in Southeastern Europe (SEE) is a reflection of the turbulent and complex demographic history of this area, influenced by gene flow from various parts of Eurasia and a long history of intermixing. Our results of 1035 samples (488 from Croatia, 239 from Bosnia and 130 from Herzegovina, reported earlier, and 97 Slovenians and 81 individuals from Zumberak, reported here for the first time) show that the SEE maternal genetic diversity fits within a broader European maternal genetic landscape. The study also shows that the population of Zumberak, located in the continental part of Croatia, developed some unique mtDNA haplotypes and elevated haplogroup frequencies due to distinctive demographic history and can be considered a moderate genetic isolate. We also report seven samples from the Bosnian population and one Herzegovinian sample designated as X2* individuals that could not be assigned to any of its sublineages (X2a'o) according to the existing X2 phylogeny. In an attempt to clarify the phylogeny of our X2 samples, their mitochondrial DNA has been completely sequenced. We suppose that these lineages are signs of local microdifferentiation processes that occurred in the recent demographic past in this area and could possibly be marked as SEE-specific X2 sublineages.

Should MS be treated by escalation or induction therapy?

MS is a chronic, increasingly disabling disease whose long-term outcomes determine the key social, medical and economic impact of this disease. Disease-modifying therapies (DMTs) for multiple sclerosis (MS) are prescribed to delay disease progression and to protect a patient's functional capability. The concepts of escalation and induction immunotherapy in MS represent different therapeutic strategies for the treatment of MS. Both strategies may be valuable options for patients starting on DMT, however, induction therapy mainly focuses on patients with very aggressive course of MS from the onset. Using a patient unique approach to selection of treatment, MS can be effectively control disease and may delay or even prevent the development of secondary progressive MS.

Prevalence of the metabolic syndrome in the old institutionalized people in Zagreb, Croatia.

Metabolic syndrome (MeS) is defined by a cluster of abnormalities comprising obesity, hypertension, carbohydrate intolerance and dyslipidemia. MeS increases the risk of developing various diseases, including coronary heart disease, stroke, peripheral angiopathy and type 2 diabetes. In our study, the subjects were 561 persons, residents of 11 homes for the elderly in Zagreb, Croatia. There were 160 men (28.5%) and 401 women (71.5%), aged from 56 to 96 years (the average being 79 years). Physical examination was conducted, which included blood pressure measurement, and body height and weight. Blood samples were taken for biochemical analysis. Along with other biochemical parameters, the levels of glucose, triglycerides and cholesterol (LDL, HDL-C) were also measured. The results have shown the prevalence of MeS in the elderly instutionalised people to be in the range of 20.8%, according to WHO criteria. The most common MeS component was hypertension, and it was significantly more frequent in women than in men; also, the elevated triglyceride levels were more often found in women; the difference between men and women was also statistically significant. MeS is a serious and growing health problem not only in Croatia but worldwide as well. Further studies are needed to verify the prevalence of MeS in Croatia, as it is a major risk for CVD and many other severe diseases.

Deep venous thrombosis post mechanical thrombectomy in acute ischaemic stroke.

A woman in her 20s presented with neck pain, slurred speech and left-sided weakness. She successfully underwent mechanical thrombectomy (MT) for total occlusion of the basilar artery and made full neurological recovery. Initial ultrasound Doppler of legs (USDL) did not show any deep vein thrombosis (DVT). However, 2 days later, a repeat USDL revealed an extensive proximal DVT in the right common femoral vein. CT scan confirmed a haematoma arising from the femoral access site causing compression of the adjacent common femoral vein. This may have initiated DVT formation or exacerbated extension of a previously undetected DVT. Echocardiogram revealed a patent foramen ovale. As the patient was asymptomatic, delayed or missed diagnosis of DVT would have put her at risk of life-threatening pulmonary embolism or further strokes. Clinicians should maintain a high index of suspicion of DVT as a direct procedural complication from MT so treatment can be initiated promptly.

Electrophysiological correlates activated during the Wisconsin Card Sorting Test (WCST).

In the present study we investigated changes in Event-Related Potentials (ERPs) during the Wisconsin Card Sorting Test (WCST) in order to identify cognitive processes underlying the set-shifting aspects of the task and to determine test sensitivity for frontal and prefrontal cortical areas. ERP's were recorded from a sample of 20 healthy adults while they performed a computerized version of the Grant & Berg (1948) version of the WCST, using 32-channel electroencephalogram recordings. The ERP waveforms were calculated for the set-shifting trials, or more precisely for the 2nd and the 3rd trials in the WCST series (set change condition) and compared to those associated with the last two trials in a series before the set change (set unchanged condition). The results indicated changes in central frontal and parietal electrodes during attentional set-shifting. More precisely, the P300 effect was replicated in this dataset, confirming the claim that the WCST measures function of prefrontal cortical areas of the brain. However, the obtained wave resembled P3b indicating the working memory component of the task. The results suggest that the frontal and parietal cortical activity is especially involved in set-shifting during WCST performance. Therefore, these electrophysiological results are not consistent with some recent studies that question the specificity of WCST as a measure of frontal and parietal lesions.

Hearing in children with otitis media with effusion--clinical retrospective study.

Hearing loss accompanied with middle ear effusion was analyzed according to audiometric frequencies for different age group. Results for left and right ears were compared in/and between study and control group. Pure tone audiometry for bone and air conduction and tympanometry was performed in study group of ninety-eight children with conductive hearing loss and otitis media with effusion. Control group included fifty-seven children with hearing loss, enlarged adenoids, dysfunction of Eustachian tube and no present middle ear effusion served. Means of hearing loss thresholds for 250 Hz-4 kHz were established and compared between groups of right vs. left ears of tested vs. control ears according to age subgroups: 1-3 yr, 4-6 yr, 7-9 yr, 10-12 yr, 13-15 yr. At age 1-3 yr otitis media with effusion children showed no ear side difference in hearing loss. Age groups of 4-6 and 7-9 yr otitis media with effusion children showed left ears with higher threshold of hearing loss across all of the tested frequencies than right ears in study and control ears. Right ears showed smaller hearing loss in study and control group and no age group predicted for hearing impairment. Higher hearing loss threshold for 4 kHz in adolescence in otitis media with effusion ears is early sign of sequels after repetitive episodes of middle ear effusion. Control groups showed no ear side or age group dependent difference of hearing loss threshold. Age group of 4-6 and 7-9 y have faster craniofacial structural change in soft tissue than bone base so ear side differences suggest being developmentally determined.

Predictors of short-term neurocognitive outcome following coronary revascularisation (CABG) depending on the use of cardiopulmonary bypass.

The purpose of our study was to investigate the association between perioperative cerebral microembolization, expressed as high-intensity transient signals (HITS) and postoperative dynamics of the neuromarker S100P in patients operated using cardiopulmonary bypass, and to assess their impact upon the neurocognitive function in the early postoperative stage. The study involved 62 consecutive male patients aged 60 or above, alls scheduled for elective aortocoronary bypass. The patients were recruited from two groups with respect to the use of CPB: on-pump group (CPB+, N = 30) and off-pump group (CPB-, N = 32). In all patients we performed intraoperative monitoring of cerebral haemodynamics using transcranial Doppler, with the goal of quantifying perioperative cerebral microembolization. The serum levels of the neuromarker S100l were measured immediately after surgery, and then 12, 24 and 48 hours after the surgery. Neurocognitive status was assessed before and after the surgery and in three cognitive domains. Results of the study have shown that with respect to the short-term postoperative neurocognitive outcome there is no significant difference between the on-pump and off-pump surgical technique of coronary revascularization'. Perioperative cerebral microembolization was significantly more pronounced in the on-pump group yet it did not affect early postoperative neurocognitive function, while the increase in the neuromarker S100beta serum level 48 hours after surgery may have prognostic value as a predictor of postoperative neurocognitive dysfunction.

Characteristics of the hearing loss in unilateral cleft lip and palate-influence on communication.

Etiology of otitis media with effusion (OME) is still unclear and often described as multi-factorial. It is very usual finding in cleft palate population. We tested relationship between the hearing level, audiometric frequencies, aging and ear side in unilateral cleft lip and palate 101 children (UCLP) and subgroups of left (UCLP)(L) and right cleft side (UCLP)(R). Group of left ears is prone to higher frequency and more severe hearing disturbances than groups of right ears, with less chance of normalizing hearing level with aging. Characteristics of hearing loss level and its improvement, in UCLP children depend of cleft type, ear side and age group.

After 40 years gossypiboma caused spleen abscess.

We report a case of spleen abscess cased by foreign body (gossypiboma) after 40 years. After physical examination, laboratory, ultrasonography and CT findings with diagnosis of acute abdomen, 73 years old woman had undergone laparatomy. Operation revealed intraabdominal spleen abscess. Capsulotomy and drainage of the collection was performed before splenectomy. Histological examination showed foreign body material surrounded by chronic inflammation, foreign body-type multinucleated giant cells, extravasated red blood cells and fibroblastic proliferation. From anamnesis we found that woman was operated only once during a life with diagnosis of extrauterine pregnancy, 40 years ago. Spleen abscess caused by gossypiboma after 40 years was never described before. However, diagnosis like this is very well known but rarely published because medical-legal implication. Education, professionalism and cooperation of all persons involved in surgical procedure are very important to prevent accidentally mistakes.

Dynamics of inflammatory factors expression in ischemic brain tissue injury.

Ischemic stroke is one of the most common cause of mortality and disability in the modern world. Still, therapeutic options remain modest. Aim of the study was to present dynamics of inflammatory factors expression (C reactive protein, procalcitonin, interleukin 10) in patients after ischemic stroke. Our study included 101 patients divided in thrombolised and nonthrombolised groups. Inflammatory factors concentration in serum was determinate at admission, 24, 48 hours and seven days after the initial onset, while neurological assessment was measured at the admission, 24 hours, seven days and three months after the initial onset using National Institute of Health Stroke Scale and Rankin Scale. Certain pattern was observed in dynamics of inflammatory factors: intensive increase in first and second day after the stroke, followed by decrease till day seven in both groups. Additionally, thrombolised group showed significant neurological improvement. Although well investigated, the role of inflammatory factors in the ischemic stroke still stays controversial. High association of C reactive protein and interleukin 10 values suggest potential prognostic role in patient's follow-up, while the role of procalcitonin values still remains unclear.

[Influence of electrical cardioversion on troponine I and brain natriuretic peptide (NT-proBNP) levels in patients with persistent atrial fibrillation/flutter]. / Utjecaj elektrokonverzije na vrijednosti troponina I i mozdanog natriuretskog peptida (NT-proBNP) u bolesnika s perzistentnom fibrilacijom/undulacijom atrija.

The goal of our research was to determine how electrical cardioversion influences troponine I and brain natriuretic peptide (NT-proBNP) levels in patients with persistent atrial fibrillation (AF), without heart failure. Reaserch was conducted on 20 patients with AF. Before and after cardioversion levels of troponine I, creatine-kinase (CK), lactate-dehydrogenase (LDH) and brain natriuretic peptide (NT-proBNP) were measured. Average total applied energy was 344,2 +/- 268,9 Joule. After cardioversion CK level was insignificantly higher (113,3:259,0). Levels of troponine I did not change significantly after cardioversion (0,185:0,202). By measuring levels of NT-proBNP significantly lower levels of NT-proBNP were found after cardioversion (1095:432). There was a strong correlation between the duration of arrhythmia and the NT-proBNP level. Electrical cardioversion with standard recommended energy does not cause significant myocardial lesion. CK level elevation is a consequence of skeletal muscle lesion. Possible elevation of troponine I should be interpreted by another etiology. Increased production of BNP is caused by increased pressure and volume overload of the atrium, in patients with AF, independent of global cardiac function, according to that we think that in patients with AF discriminatory values of BNP in heart failure diagnostics should be corrected to higher levels.

Lesson of the month 2: Use of thrombolysis for ischaemic stroke in pregnancy - a case report and review of literature.

A nine-week pregnant 33-year-old female presented with sudden-onset right-sided hemiparesis, hemisensory loss, dysarthria and homonymous hemianopia. She was known to have eleven previous miscarriages and used recreational drugs. A CT-head was unremarkable. The patient was subsequently diagnosed with an acute thromboembolic infarct and chose alteplase after counselling. During thrombolysis an ultrasound identified a foetus with no concerning features. A post-thrombolysis CT revealed a left-sided posterior cerebral infarct. CT-venography, carotid Doppler, 72-hour Holter monitor, thrombophilia and an autoimmune screen were all normal. A transthoracic echocardiogram demonstrated a mobile intra-atrial septum with a patent foramen ovale confirmed on bubble echocardiogram. Three days post-thrombolysis the patient requested a termination of pregnancy. A subsequent transvaginal ultrasound demonstrated a missed miscarriage for which the patient underwent evacuation of retained products of conception. Multidisciplinary care ensured that her sensorimotor deficit resolved grossly with only mild dysarthria and right-hand fine motor incoordination.

Difficulties with diagnosis and consequential poor outcome due to stigma of acquired immunodeficiency syndrome - a case report.

Low incidence of human immunodeficiency virus (HIV) infections and acquired immunodeficiency syndrome (AIDS) has been detected in Croatia so far. Toxoplasmic encephalitis (TE) is the most common opportunistic cerebral infection in AIDS patients and is highly responsive to antiparasitic chemotherapy, if treated at an early stage. We present the case of the brain biopsy confirmed as TE on a 36-year-old female patient who at admission presented with unconsciousness and a right hemiplegia. A MSCT was performed and two hypodense lesions were diagnosed. The patient's family initially denied the presence or history of any medical problem or infection. An MRI showed multiple ring-enhanced mass lesions. An infectologist required a brain biopsy to exclude cerebral lymphoma and multiple metastases. Pathohistological analysis suggested TE. Meanwhile, patient's blood samples were found to be HIV positive. The patient was transferred to University Hospital for Infectious Diseases in Zagreb, where she died 2 days following admission. The patient's family terminally confessed that the patient had been HIV positive for 10 years and had refused any treatment. Family's denial of infection as well as 'hiding information' concerning patient's health from physicians involved in her treatment caused a delay in proper on-time patient treatment. We would like to emphasize that TE must be considered as a differential diagnosis in patients presenting with multiple cerebral lesions, including patients without acknowledged past history of HIV infection. A stigma towards HIV infection and ignorance of the disease still exist and therefore hinders proper treatment.

Diffuse skin hyperpigmentation in CD30+ lymphoproliferation.

CD30+ T-cell lymphoproliferative disorders (LD) comprise two main groups of diseases: CD30+ LD of the skin and systemic anaplastic large cell lymphoma (ALCL). The main feature of these disorders is the expression of CD30. We present a patient with an unusual clinical presentation of CD30+ lymphoproliferative disease in a 54-year old Caucasian male who presented with generalized lymphadenopathy and pronounced skin hyperpigmentation. In the lymph nodes and skin, CD30+ lymphoproliferation (ALCL) was diagnosed. The Prussian blue staining identified that the pigment responsible for the skin color was hemosiderin. Chemotherapy was started but the patient's condition progressively worsened and he died a week after the first cycle. The complete color transformation of the entire skin due to hemosiderin accumulation is, to the best of our knowledge, the first reported observation in a CD30+ lymphoproliferation/ALCL patient. We speculate that hemosiderin-loaded macrophages resulted from the paraneoplastic process by some still unknown mechanism.