The effect of single nucleotide polymorphisms and mutations on congenital thrombotic thrombocytopenic purpura phenotype

Thrombotic thrombocytopenic purpura (TTP) is a rare, life-threatening disease with a reported incidence of 6 cases per million per year in the UK. It is characterised by episodes of microangiopathic haemolytic anaemia and thrombocytopenia, with the widespread presence of platelet-rich thrombi in the microcirculation, leading to end-organ damage. TTP is a clinically heterogeneous disorder caused by autoantibody inhibition or clearance or by a deficiency in activity or secretion of the von Willebrand factor cleaving protease (ADAMTS13). Over 100 mutations have been identified in ADAMTS13 yet, in some cases, these mutations in congenital TTP alone do not explain the disease phenotype, particularly in late-onset congenital TTP. One aim of this study was to analyse the effect of single nucleotide polymorphisms (SNPs), in conjunction with ADAMTS13 mutations, which have been identified in a cohort of TTP patients with varied clinical phenotype. Twenty mutant expression plasmids containing an ADAMTS13 mutation and/or SNP have been constructed by site-directed mutagenesis (SDM). Fourteen plasmids contained a new non-synonymous mutation (C3484T) which has been rectified by further SDM. After full sequencing of the plasmid ADAMTS13 insert, 24 clones were identified as viable and the resultant protein was expressed in HEK293T cells and analysed by Western blot and ADAMTS13 antigen ELISA. Blots were scanned by densitometry and the intensity of the protein species corresponding to ADAMTS13 determined using ImageJ. The predicted effects of mutations and/or SNPs were annotated by the in silico computational tools SIFT, PolyPhen2, I-Mutant 2.0 and SNPEffect 4.0.Results from this genotype study were compared to clinical phenotype by correlating data held within the TTP Registry at University College London. The resultant analysis showed the mutations located in the N-terminal end of ADAMTS13 protein induced more secretory defects and SNPs had less of an effect on phenotype. The p.R7W and p.A1033T SNPs showed more of an effect on secretion of ADAMTS13 when the mutation was located in the Cterminal end (p.R1060W) which is associated with late-onset phenotype. However, other environmental factors such as changes in the ADAMTS13-VWF axis during pregnancy and infection make a correlation between genotype and phenotype in TTP more challenging

Personality disorder in primary care : factors associated with therapy process and outcome.

Assessment and treatment of personality disorder (PD) is a key issue in UK mental health service provision (NIMH report, 2003), but there is limited information on individuals with personality disorder presenting to primary care mental health services. This study investigates the characteristics of PD in individuals receiving cognitive behaviour therapy (CBT) following GP referral and its relationship with therapist ratings of treatment process and outcome. One hundred and forty-eight participants completed the Millon Multiaxial Clinical Inventory (MCMI-III: Millon, Davis and Millon, 1997). Therapists completed a measure of therapy process and outcome (TPOQ) on 100 participants. Key therapy and process questions were answered for 60 participants who attended a minimum of five therapy sessions. MCMI-III indicated a rate of PD of 56.4%. Factor analysis of PD scales identified two factors: inward looking/emotionally distanced, and aggressive/acting out. For clinical syndromes (CLS), the factors were general psychopathology and substance abuse. TPOQ had two factors: therapeutic alliance and complexity in therapy. Regression analyses indicated that only those PDs contributing to the inward looking/emotionally distanced scale score were associated with therapeutic alliance problems. Conversely, complexity in therapy was only predicted by general psychopathology and not by personality disorder. This study identified high rates of personality disorder in primary care referrals to a clinical psychology service. It also indicated that relationships between the presence of personality disorder and therapist ratings of treatment difficulties were only associated with certain types of personality disorder. These findings are discussed in relation to service and therapy planning in mental health

Further Notes on the Kikuyu Tribe of British East Africa

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Perceived familial socialization and ethnic identity: factors associated with physical activity, eating behavior patterns, and social physique anxiety in african american middle adolescents

Purpose: African American adolescents experience higher rates of obesity and have an increased risk of obesity related diseases than Caucasian American adolescents. Despite culturally sensitive obesity preventive interventions, obesity rates are increasing within the African American adolescent population. Current obesity interventions claim to be culturally sensitive, but do not address how ethnic identity and parental influences on body image and body change may affect the efficacy of the interventions. The purpose of this study was to examine the sociocultural factors related to weight behaviors and cognitions in African American adolescents. Differences based on socioeconomic status (SES), gender, and residential status provided the context for the analysis. Theoretical Framework: The social ecological approach was used to guide the study in the exploration of parental influences on body image and body change as the variables related to the sociocultural norms in the weight behaviors and cognitions of social physique anxiety, eating behaviors, and physical activity in African American adolescents. Methodology: A descriptive correlational design was utilized. The sample (n = 145) included African American adolescents, ages 15 to 17 from community clinics, youth organizations, churches, and social networks in metropolitan and inner city Detroit. Data were collected utilizing survey methods and analyzed using descriptive statistics, Pearson Product Moment Correlations, and Independent Sample t tests. Findings: Adolescents in the study reported consuming diets high in fat and calories, low physical activity levels, and moderate amounts of social physique anxiety. Perceived parental socialization, specifically maternal socialization, was significantly related to the adolescents\u27 eating behaviors, physical activity, and social physique anxiety, while paternal socialization was only significantly related to their physical activity and social physique anxiety. The adolescents\u27 ethnic identity was not significantly related to their eating behaviors, physical activity, or social physique anxiety. There were significant group differences in the major study variables and weight measurement based on gender, socioeconomic status, and residential status. Conclusions: The initial findings from the study will assist in better understanding the factors related to behaviors and cognitions that are related to the obesity epidemic that affects the African American adolescents in disparate proportions. Further examination of the variables is essential in order to serve as a basis for developmentally appropriate and culturally relevant targeted interventions with this population. Nurses and health care providers who work with youth can utilize the initial findings from this study to be the advocates of healthy lifestyles while reducing the obesity disparity within the African American adolescent population

Becoming His Work By Hearing His Word: A Gospel Communication Plan For Bellwether Church

The goal of this study is to develop a communication plan for Bellwether Community Church. It is argued throughout the paper that this church, located in the Bible Belt, needs a comprehensive program to assist its congregation in living out the gospel through discipleship, apologetics, and evangelism. This program is implemented in Bellwether Community Church over a two–year timeframe. This program emphasizes preaching as the primary means of communication and the overall plan focuses on the preaching series. However, preaching is only one means of the plan, as it also includes intentional equipping classes, small group curriculum, written devotions, and creative works of writing. All these forms emphasize an increased aptitude for the congregation in apologetics, evangelism, and discipleship. The goals for the church are to have a unity of communication over the course of the program, the congregation to be unified in its participation, individual participants to grow in the areas of apologetics, discipleship, and evangelism, and the church to grow in greater knowledge of Scripture and outreach into its local community. Prior to the program’s launch, time is given for prayer and planning, engaging staff, leaders, and members in discussion, and preparing small group leaders to facilitate curriculum. Upon its launch, there is a centralized focus on the program’s teaching and consistent encouragement for the church to engage in all its aspects. There are assessments of the program where participants give feedback and church leaders can see its effectiveness. Upon completion, this overarching program can impact discipleship within any church community. It can also be modified for this church in its next season and offered to other churches for use

THE BIOLOGY OF THE TROPICAL CATTLE TICK AND OTHER SPECIES OF TICK IN PUERTO RICO, WITH NOTES ON THE EFFECTS ON TICKS OF ARSENICAL DIPS

For many years the presence of the tropical cattle tick, Boophilus annulatus microplus (Can.) (australis Fuller), in Puerto Rico has been a serious impediment to the development of the cattle industry in that island. In addition to heavy losses occasioned by tick infestation alone, the role of these ectoparasites in the transmission of tick fever of cattle has resulted in enormous losses and has presented an obstacle to the introduction of the better breeds of non-immune stock from tick-free areas

Multi-Satellite Attitude Prediction program/Orbiting Solar Observatory-8 (MSAP/OSO-8) operating guide

The sun's lower corona and chromosphere and their interaction in the X-ray and ultraviolet (UV) spectral regions were investigated to better understand the transport of energy from the photosphere to the corona. The interaction between the solar electromagnetic and particle radiation and the earth's environment was studied and the background component of cosmic X-rays was discussed