AIMS: We hypothesized that during left bundle branch (LBB) area pacing, the various possible combinations of direct capture/non-capture of the septal myocardium and the LBB result in distinct patterns of right and left ventricular activation. This could translate into different combinations of R-wave peak time (RWPT) in V1 and V6. Consequently, the V6-V1 interpeak interval could differentiate the three types of LBB area capture: non-selective (ns-)LBB, selective (s-)LBB, and left ventricular septal (LVS). METHODS AND RESULTS: Patients with unquestionable evidence of LBB capture were included. The V6-V1 interpeak interval, V6RWPT, and V1RWPT were compared between different types of LBB area capture. A total of 468 patients from two centres were screened, with 124 patients (239 electrocardiograms) included in the analysis. Loss of LVS capture resulted in an increase in V1RWPT by ≥15 ms but did not impact V6RWPT. Loss of LBB capture resulted in an increase in V6RWPT by ≥15 ms but only minimally influenced V1RWPT. Consequently, the V6-V1 interval was longest during s-LBB capture (62.3 ± 21.4 ms), intermediate during ns-LBB capture (41.3 ± 14.0 ms), and shortest during LVS capture (26.5 ± 8.6 ms). The optimal value of the V6-V1 interval value for the differentiation between ns-LBB and LVS capture was 33 ms (area under the receiver operating characteristic curve of 84.7%). A specificity of 100% for the diagnosis of LBB capture was obtained with a cut-off value of >44 ms. CONCLUSION: The V6-V1 interpeak interval is a promising novel criterion for the diagnosis of LBB area capture.

• MeSH
• Electrocardiography methods   MeSH
• Bundle of His * MeSH
• Cardiac Pacing, Artificial methods   MeSH
• Humans MeSH
• Ventricular Septum * MeSH
• Heart Conduction System MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH

The most common histological subtypes of cutaneous melanoma include superficial spreading and nodular melanoma. However, the spectrum of somatic mutations developed in those lesions and all potential druggable targets have not yet been fully elucidated. We present the results of a sequence capture NGS analysis of 114 primary nodular and superficial spreading melanomas identifying driver mutations using biostatistical, immunohistochemical and/or functional approach. The spectrum and frequency of pathogenic or likely pathogenic variants were identified across 54 evaluated genes, including 59 novel mutations, and the newly identified TP53 loss-of-function mutations p.(L194P) and p.(R280K). Frequently mutated genes most commonly affected the MAPK pathway, followed by chromatin remodeling, and cell cycle regulation. Frequent aberrations were also detected in the genes coding for proteins involved in DNA repair and the regulation and modification of cellular tight junctions. Furthermore, relatively frequent mutations were described in KDR and MET, which represent potential clinically important targets. Those results suggest that with the development of new therapeutic possibilities, not only BRAF testing, but complex molecular testing of cutaneous melanoma may become an integral part of the decision process concerning the treatment of patients with melanoma.

• MeSH
• Cell Cycle genetics   MeSH
• Adult MeSH
• Gene Frequency genetics   MeSH
• Genetic Predisposition to Disease genetics   MeSH
• Middle Aged MeSH
• Humans MeSH
• MAP Kinase Signaling System genetics   MeSH
• Melanoma genetics   pathology   MeSH
• Young Adult MeSH
• Loss of Function Mutation genetics   MeSH
• Biomarkers, Tumor genetics   MeSH
• Tumor Suppressor Protein p53 genetics   MeSH
• Skin Neoplasms genetics   pathology   MeSH
• DNA Repair genetics   MeSH
• Proto-Oncogene Proteins B-raf genetics   MeSH
• Chromatin Assembly and Disassembly genetics   MeSH
• Aged, 80 and over MeSH
• Aged MeSH
• Tight Junctions genetics   MeSH
• High-Throughput Nucleotide Sequencing MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Young Adult MeSH
• Male MeSH
• Aged, 80 and over MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH

Four accessions of hexaploid Elymus repens from its native Central European distribution area were analyzed using sequencing of multicopy (internal transcribed spacer, ITS) and single-copy (granule-bound starch synthase I, GBSSI) DNA in concert with genomic and fluorescent in situ hybridization (GISH and FISH) to disentangle its allopolyploid origin. Despite extensive ITS homogenization, nrDNA in E. repens allowed us to identify at least four distinct lineages. Apart from Pseudoroegneria and Hordeum, representing the major genome constituents, the presence of further unexpected alien genetic material, originating from species outside the Triticeae and close to Panicum (Paniceae) and Bromus (Bromeae), was revealed. GBSSI sequences provided information complementary to the ITS. Apart from Pseudoroegneria and Hordeum, two additional gene variants from within the Triticeae were discovered: One was Taeniatherum-like, but the other did not have a close relationship with any of the diploids sampled. GISH results were largely congruent with the sequence-based markers. GISH clearly confirmed Pseudoroegneria and Hordeum as major genome constituents and further showed the presence of a small chromosome segment corresponding to Panicum. It resided in the Hordeum subgenome and probably represents an old acquisition of a Hordeum progenitor. Spotty hybridization signals across all chromosomes after GISH with Taeniatherum and Bromus probes suggested that gene acquisition from these species is more likely due to common ancestry of the grasses or early introgression than to recent hybridization or allopolyploid origin of E. repens. Physical mapping of rDNA loci using FISH revealed that all rDNA loci except one minor were located on Pseudoroegneria-derived chromosomes, which suggests the loss of all Hordeum-derived loci but one. Because homogenization mechanisms seem to operate effectively among Pseudoroegneria-like copies in this species, incomplete ITS homogenization in our samples is probably due to an interstitial position of an individual minor rDNA locus located within the Hordeum-derived subgenome.

• MeSH
• Bayes Theorem MeSH
• Cytogenetic Analysis methods   MeSH
• Databases, Genetic MeSH
• Phylogeny MeSH
• Transcription, Genetic MeSH
• In Situ Hybridization, Fluorescence MeSH
• DNA, Intergenic MeSH
• Poaceae genetics   MeSH
• Models, Genetic MeSH
• Gene Transfer, Horizontal MeSH
• Pseudogenes MeSH
• DNA, Ribosomal MeSH
• Genes, Plant MeSH
• Starch Synthase genetics   MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH

OBJECTIVE: This study aimed to clarify the molecular epidemiology of hearing loss by identifying the responsible genes in patients without GJB2 mutations. STUDY DESIGN: Prospective genetic study. SETTING: Tertiary referral hospital. PATIENTS: Fifty one patients with bilateral sensorineural hearing loss, 20 men, and 31 women, mean age 24.9 years, range 3 to 64 years, from 49 families. GJB2 and deltaGJB6-D13S1830 mutations were excluded previously. INTERVENTION: Diagnostic. Sixty-nine genes reported to be causative of hearing loss were analyzed. Sequence capture technology, next-generation sequencing, and multiplex ligation-dependent probe amplification (MLPA) were used. Coverage of STRC was screened in Integrative Genomics Viewer software. MAIN OUTCOME MEASURE: Identification of causal pathogenic mutations in genes related to deafness. RESULTS: Five families (10%) had recessive STRC deletions or mutations. Five unrelated patients (10%) had recessive mutations in TMPRSS3, USH2A, PCDH15, LOXHD1, and MYO15A. Three families (6%) had autosomal dominant mutations in MYO6A, KCNQ4, and SIX1. One family (2%) had an X-linked POU3F4 mutation. Thus, we identified the cause of hearing loss in 28% of the families studied. CONCLUSIONS: Following GJB2, STRC was the second most frequently mutated gene in patients from the Czech Republic with hearing loss. To decrease the cost of testing, we recommend STRC deletion screening with MLPA before next-generation sequencing. The existence of a pseudogene and polymorphic STRC regions can lead to false-positive or false-negative results when copy number variation analysis is based on next-generation sequencing data.

• MeSH
• Child MeSH
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Membrane Proteins genetics   MeSH
• Adolescent MeSH
• Young Adult MeSH
• Mutation MeSH
• Hearing Loss, Sensorineural congenital   genetics   MeSH
• Child, Preschool MeSH
• Prospective Studies MeSH
• Check Tag
• Child MeSH
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Adolescent MeSH
• Young Adult MeSH
• Male MeSH
• Child, Preschool MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Geographicals
• Czech Republic MeSH

A confocal laser scanning microscope (CLSM) enables us to capture images from a biological specimen in different depths and obtain a series of precisely registered fluorescent images. However, images captured from deep layers of the specimen may be darker than images from the topmost layers because of light loss distortions. This effect causes difficulties in subsequent analysis of biological objects. We propose a solution using two approaches: either an online method working already during image acquisition or an offline method assisting as a postprocessing step. In the online method, the gain value of a photomultiplier tube of a CLSM is controlled according to the difference of mean image intensities between the reference and currently acquired image. The offline method consists of two stages. In the first stage, a standard histogram maintaining relative frequencies of gray levels and improving brightness and contrast is created from all images in the series. In the second stage, individual image histograms are warped according to this standard histogram. The methods were tested on real confocal image data captured from human placenta and rat skeletal muscle specimens. It was shown that both approaches diminish the light attenuation in images captured from deep layers of the specimen.

• MeSH
• Financing, Organized MeSH
• Microscopy, Confocal methods   MeSH
• Muscle, Skeletal cytology   MeSH
• Rats MeSH
• Humans MeSH
• Placenta cytology   MeSH
• Image Processing, Computer-Assisted methods   MeSH
• Pregnancy MeSH
• Image Enhancement methods   MeSH
• Animals MeSH
• Check Tag
• Rats MeSH
• Humans MeSH
• Pregnancy MeSH
• Female MeSH
• Animals MeSH

• MeSH
• Neoplasms radiotherapy   MeSH
• Nuclear Medicine methods   MeSH
• Radiotherapy methods   MeSH
• Publication type
• Textbook MeSH

• Conspectus
• Učební osnovy. Vyučovací předměty. Učebnice
• Lékařské vědy. Lékařství
• NML Fields
• radiologie, nukleární medicína a zobrazovací metody
• onkologie
• NML Publication type
• kolektivní monografie

AIMS: Permanent His-bundle (HB) pacing is usually accompanied by simultaneous capture of the adjacent right ventricular (RV) myocardium-this is described as a non-selective (ns)-HB pacing. It is of clinical importance to confirm HB capture using standard electrocardiogram (ECG). Our aim was to identify ECG criteria for loss of HB capture during ns-HB pacing. METHODS AND RESULTS: Patients with permanent HB pacing were recruited. Electrocardiograms during ns-HB pacing and loss of HB capture (RV-only capture) were obtained. Electrocardiogram criteria for loss/presence of HB capture were identified. In the validation phase, these criteria and the 'HB ECG algorithm' were tested using a separate, sizable set of ECGs. A total of 353 ECG (226 ns-HB and 128 RV-only) were obtained from 226 patients with permanent HB pacing devices. QRS notch/slur in left ventricular leads and R-wave peak time (RWPT) in lead V6 were identified as the best features for differentiation. The 'HB ECG algorithm' based on these features correctly classified 87.1% of cases with sensitivity and specificity of 93.2% and 83.9%, respectively. The criteria for definitive diagnosis of ns-HB capture (no QRS slur/notch in Leads I, V1, V4-V6, and the V6 RWPT ≤ 100 ms) presented 100% specificity. CONCLUSION: A novel ECG algorithm for the diagnosis of loss of HB capture and criteria for definitive confirmation of HB capture were formulated and validated. The algorithm might be useful during follow-up and the criteria for definitive confirmation of ns-HB capture offer a simple and reliable ancillary procedural endpoint during HB device implantation.

• MeSH
• Algorithms * MeSH
• Atrioventricular Block therapy   MeSH
• Electrocardiography methods   MeSH
• Atrial Fibrillation therapy   MeSH
• Bundle of His * MeSH
• Cardiac Pacing, Artificial * MeSH
• Middle Aged MeSH
• Humans MeSH
• Aged, 80 and over MeSH
• Aged MeSH
• Heart Failure therapy   MeSH
• Sick Sinus Syndrome therapy   MeSH
• Check Tag
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Aged, 80 and over MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Validation Study MeSH

Mountain butterflies have evolved efficient thermoregulation strategies enabling their survival in marginal conditions with short flight season and unstable weather. Understanding the importance of their behavioural thermoregulation by habitat use can provide novel information for predicting the fate of alpine Lepidoptera and other insects under ongoing climate change. We studied the link between microhabitat use and thermoregulation in adults of seven species of a butterfly genus Erebia co-occurring in the Austrian Alps. We captured individuals in the field and measured their body temperature in relation to microhabitat and air temperature. We asked whether closely related species regulate their body temperature differently, and if so, what is the effect of behaviour, species traits and individual traits on body to air and body to microhabitat temperature differences. Co-occurring species differed in mean body temperature. These differences were driven by active microhabitat selection by individuals and also by species-specific habitat preferences. Species inhabiting grasslands and rocks utilised warmer microclimates to maintain higher body temperature than woodland species. Under low air temperatures, species of rocky habitats heated up more effectively than species of grasslands and woodlands which allowed them to stay active in colder weather. Species morphology and individual traits play rather minor roles in the thermoregulatory differences; although large species and young individuals maintained higher body temperature. We conclude that diverse microhabitat conditions at small spatial scales probably contribute to sympatric occurrence of closely related species with different thermal demands and that preserving heterogeneous conditions in alpine landscapes might mitigate detrimental consequences of predicted climate change.

• MeSH
• Biodiversity * MeSH
• Butterflies physiology   MeSH
• Altitude MeSH
• Temperature MeSH
• Body Temperature Regulation * MeSH
• Animals MeSH
• Check Tag
• Animals MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH

Obezita je chronické onemocnění charakterizované vysokou prevalencí. Snadná dostupnost farmaceutické péče umožňuje lékárnám být prvním místem záchytu nebo intervence u pacientů s nadváhou nebo obezitou. Cílem práce bylo analyzovat roli farmaceuta a farmaceutického asistenta (FA) jako garantů bezpečného samoléčení při použití léčiva orlistat. Prospektivní observační studie byla realizována se skupinou pacientů, která navštívila Ústavní lékárnu IKEM za účelem samoléčení orlistatem v období květen až prosinec 2009. Sběr dat byl realizován proškolenými farmaceuty a FA během dispenzace orlistatu v režimu OTC (over-the-counter) formou pohovoru s pacientem. Pohovor byl veden pomocí předem stanovených otázek z formuláře. Data byla vyhodnocena pomocí frekvenční analýzy, GLMz a chí-kvadrát testu (p < 0,05). Do studie bylo zahrnuto 50 pacientů (44 žen, medián věku 53 let, 41 pacientů s BMI > 28). Z celkového souboru mělo 58 % pacientů plnou indikaci k samoléčení orlistatem. Samoléčení bylo doporučeno u 48 % pacientů a u 22 % bylo zamítnuto z důvodu kontraindikací. U 24 % pacientů se vyskytovala alespoň jedna léková interakce orlistatu s chronicky užívanými léčivy. Nejčastější motivací ke snižování hmotnosti byly zdravotní potíže. Data získaná touto studií dokládají nezastupitelnost farmaceutů a FA při posuzování vhodnosti léčiva orlistat v režimu OTC a při bezpečném snižování hmotnosti formou samoléčení. Klíčová slova: obezita • orlistat • farmaceutická péče • samoléčení

Obesity is a chronic disease characterized by its high prevalence. Easy availability of pharmaceutical care allows pharmacies to be the first place of capture or intervention for patients who are overweight or obese. The aim of the study was to analyse the role of pharmacists and pharmacy technicians in securing the safety of self-medication with orlistat. In this prospective observational study, the patients were the people who came to the IKEM Hospital Pharmacy for self-medication with orlistat over a period of May through December 2009. The data were collected by trained pharmacists and pharmacy technicians in interviews with patients when dispensing over-the-counter (OTC) orlistat. The interview was designed by fixed questions. The results were analysed using frequency analysis, GLMz and the chi-square test with the level of significance of p < 0.05. A total of 50 patients participated in the study (44 women, median age 53 years, 41 patients with body mass index > 28). 58% patients were fully indicated for self-medication with orlistat. Self-medication with orlistat was recommended to 48% patients and was refused to 22% patients because of contraindications. 24% patients had at least one interaction with orlistat and chronic drugs. Health problems were the most common motivation for weight reduction. The data obtained in this study demonstrate an important role of pharmacists and pharmacy technicians in the assessment of suitability of self-medication with OTC orlistat and safe weight reduction within self-medication. Key words: obesity • pharmaceutical care • orlistat • self-medication Received 7 November 2012 / Accepted 28 November 2012

• MeSH
• Pharmaceutical Services MeSH
• Anti-Obesity Agents MeSH
• Nonprescription Drugs MeSH
• Middle Aged MeSH
• Humans MeSH
• Obesity * drug therapy   MeSH
• Professional Role MeSH
• Self Medication * MeSH
• Check Tag
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Female MeSH
• Publication type
• Research Support, Non-U.S. Gov't MeSH

Hajdu-Cheney syndrome (HCS) is a rare multi-system disease with autosomal dominant inheritance and skeletal involvement, resulting mostly in craniofacial dysmorphy with mid-face hypoplasia, dental anomalies, short stature, scoliosis, shortening of the digits and nail beds, acro-osteolysis and osteoporosis. We report the progression of clinical and radiographic findings in five patients with Hajdu-Cheney syndrome from two families. A custom capture array designed to capture exons and adjacent intron sequences of 230 selected genes were used for molecular analyses, and the pathogenic variants identified were confirmed by PCR and Sanger sequencing. In both families we observed age-dependent changes in the disease, with a progression of pain in older patients, a shortening of digits and nail beds on both the hands and feet, kyphoscoliosis and the persistence of Wormian bones in lambdoid sutures. Molecular analyses performed in two patients revealed that they are heterozygotes for a c.6255T>A (p.Cys2085*) variant in the NOTCH2 gene, resulting in a premature stop-codon. Bone mineral density (Z-score < -2) did not improved in a girl treated with calcium and vitamin D supplementation during childhood and bisphosphonate during adolescence. Hajdu-Cheney syndrome is a slowly progressive disease with a frequently unfavourable prognosis in elderly patients, especially for the development of dental anomalies, osteoporosis and the progression of skeletal complications requiring orthopedic surgeries.

• MeSH
• Child MeSH
• Hajdu-Cheney Syndrome * complications   pathology   MeSH
• Bone Density MeSH
• Humans MeSH
• Adolescent MeSH
• Osteoporosis * etiology   MeSH
• Prognosis MeSH
• Disease Progression MeSH
• Aged MeSH
• Check Tag
• Child MeSH
• Humans MeSH
• Adolescent MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH