Genome-wide association study identifies six new loci influencing pulse pressure and mean arterial pressure.

Numerous genetic loci have been associated with systolic blood pressure (SBP) and diastolic blood pressure (DBP) in Europeans. We now report genome-wide association studies of pulse pressure (PP) and mean arterial pressure (MAP). In discovery (N = 74,064) and follow-up studies (N = 48,607), we identified at genome-wide significance (P = 2.7 × 10(-8) to P = 2.3 × 10(-13)) four new PP loci (at 4q12 near CHIC2, 7q22.3 near PIK3CG, 8q24.12 in NOV and 11q24.3 near ADAMTS8), two new MAP loci (3p21.31 in MAP4 and 10q25.3 near ADRB1) and one locus associated with both of these traits (2q24.3 near FIGN) that has also recently been associated with SBP in east Asians. For three of the new PP loci, the estimated effect for SBP was opposite of that for DBP, in contrast to the majority of common SBP- and DBP-associated variants, which show concordant effects on both traits. These findings suggest new genetic pathways underlying blood pressure variation, some of which may differentially influence SBP and DBP

New genetic loci link adipose and insulin biology to body fat distribution.

Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 × 10(-8)). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms

Interobserver Variability of Histopathological Prognostic Parameters in Cutaneous Malignant Melanoma : Impact on Patient Management

Clinical management of primary cutaneous melanomas is based on histopathological staging of the tumour. The aim of this study was to investigate, in a non-selected population in clinical practice, the agreement rate between general pathologists and pathologists experienced in melanoma in terms of the evaluation of histopathological prognostic parameters in cutaneous malignant melanomas, and to what extent the putative variability affected clinical management. A total of 234 cases of invasive cutaneous malignant melanoma were included in the study from the Stockholm-Gotland Healthcare Region in Sweden. Overall interobserver variability between a general pathologist and an expert review was 68.8-84.8%. Approximately 15.5% of melanomas &lt;= 1 mm were re-classified either as melanoma in situ or melanomas &gt;1 mm after review. In conclusion, review by a pathologist experienced in melanoma resulted in a change in recommendations about surgical excision margins and/or sentinel node biopsy in subgroups of Ti melanomas

Playing as an early-childhood promotion of communication skills

Darba autore: Agita Kaža Darba tēma: Rotaļa kā saskarsmes prasmju sekmētāja agrās bērnības vecumā Darba vadītājs: Prof. Dr. psych.Tija Zīriņa Pētījuma mērķis: Pētīt 2 – 3 gadīgu bērnu saskarsmes prasmes rotaļās Pētījuma saturs: darba teorētiskās daļas pirmajā nodaļā tiek aplūkotas un analizētas dažādu pedagogu, psihologu atziņas par saskarsmi, kā veidojas saskarsme pirmsskolā. Darba otrajā nodaļā tiek pētīta agrās bērnības saskarsmju prasmju sekmēšanā rotaļās. Nodaļas saturs lielākoties balstās uz praktisko pētījumu. Pētījumā piedalās agrās bērnības vecuma 16 bērni. Pētījumā tiek organizētas rotaļas ar kuru palīdzību bērni veicina sekmīgu saskarsmes prasmju veidošanos. Secinājumos apkopota nozīmīgākā informācija saskarsmes prasmju attīstību rotaļā. Atslēgas vārdi: saskarsme, saskarsmes prasmju attīstība, rotaļa, pirmsskola, bērni. Darba apjoms: darbs sastāv no 4 nodaļām un 5 apakšnodaļām, tam ir 55 lapas. Darbā aplūkojamas 2 tabulas, 2 attēli un pielikums, kurā ir redzams 21 attēls, izmantotās literatūras saraksts sastāv no 45 avotiem.Author of the work: Agita Kaza Theme of the work: Playing as an early-childhood promotion of communication skills Supervisor of the work: Prof. Dr. psych. Tija Zirina The aim of the research: To study 2-3-year-olds' skills in games Study content: the first chapter of the theoretical part of the work looks at and analyzes the knowledge of various educators, psychologists, about how they come into contact in preschool. The second section of work examines the promotion of early childhood communication skills in games. The content of the chapter is largely based on the practical study. 16 children of the age of early childhood are involved in the study. The study organizes games to help children develop successful communication skills. The conclusions summarise key information on the development of communication skills in play. Keywords: communication, development of communication skills, playing, preschool, children. Scope of the work: the work consists of 4 chapters and 5 subdivisions, with 55 pages. The work includes 2 tables, 2 pictures and an attachment showing 21 figures, a list of authorities used consisting of 45 sources

Different Serotonergic Expression in Nevomelanocytic Tumors

The neuromediator serotonin (5-hydroxytryptamine; 5-HT) has been proposed to play a role in tumor progression. Thus, the aim of the present investigation was to determine whether alterations in the serotonergic system occur in nevomelanocytic tumors. For this purpose, paraffin-embedded biopsies of superficial spreading malignant melanoma (SSM), dysplastic compound nevi (DN) and benign compound nevi (BCN) were characterized with regard to their expression of 5-HT, the 5-HT1A and 5-HT2A receptors, and the serotonin transporter protein (SERT), by immunohistochemical analysis. Melanocytes in the region surrounding the tumor were found to express both the 5-HT1A and 5-HT2A receptors. Tumor cells that immunostained positively for the different serotonergic markers were observed in the suprabasal epidermis of DN tissue and, to an even greater extent, in the case of SSM. Furthermore, some of these latter cells expressed both 5-HT1AR and 5-HT2AR. The level of expression of 5-HT1AR at the junctional area was lower for SSM than for DN or BCN. As the degree of atypia increased, the intensity of tumor cell staining in the dermis for 5-HT1AR and SERT declined. Vessel immunoreactivity for 5-HT2A was more intense in SSM than in BCN tissue. Round-to-dendritic cells that expressed both SERT and 5-HT1AR were seen to infiltrate into the dermal region of the tumor, this infiltration being more evident in the case of DN and SSM. These latter cells were also tryptase-positive, indicating that they are mast cells. Thus, alterations in serotonergic system may be involved in nevomelanocytic tumors and mast cells may play an important role in this connection

Genetic studies of body mass index yield new insights for obesity biology

Note: A full list of authors and affiliations appears at the end of the article. Obesity is heritable and predisposes to many diseases. To understand the genetic basis of obesity better, here we conduct a genome-wide association study and Metabochip meta-analysis of body mass index (BMI), a measure commonly used to define obesity and assess adiposity, in up to 339,224 individuals. This analysis identifies 97 BMI-associated loci (P 20% of BMI variation. Pathway analyses provide strong support for a role of the central nervous system in obesity susceptibility and implicate new genes and pathways, including those related to synaptic function, glutamate signalling, insulin secretion/action, energy metabolism, lipid biology and adipogenesis.</p