Screening families of patients with premature coronary heart disease to identify avoidable cardiovascular risk: a cross-sectional study of family members and a general population comparison group

<b>Background:</b> Primary prevention should be targeted at individuals with high global cardiovascular risk, but research is lacking on how best to identify such individuals in the general population. Family history is a good proxy measure of global risk and may provide an efficient mechanism for identifying high risk individuals. The aim was to test the feasibility of using patients with premature cardiovascular disease to recruit family members as a means of identifying and screening high-risk individuals. <b>Findings:</b> We recruited family members of 50 patients attending a cardiology clinic for premature coronary heart disease (CHD). We compared their cardiovascular risk with a general population control group, and determined their perception of their risk and current level of screening. 103 (36%) family members attended screening (27 siblings, 48 adult offspring and 28 partners). Five (5%) had prevalent CHD. A significantly higher percentage had an ASSIGN risk score >20% compared with the general population (13% versus 2%, p < 0.001). Only 37% of family members were aware they were at increased risk and only 50% had had their blood pressure and serum cholesterol level checked in the previous three years. <b>Conclusions:</b> Patients attending hospital for premature CHD provide a mechanism to contact family members and this can identify individuals with a high global risk who are not currently screened

Characterization of a recurrent missense mutation in the forkhead DNA-binding domain of \u3ci\u3eFOXP1\u3c/i\u3e

Haploinsufficiency of Forkhead box protein P1 (FOXP1), a highly conserved transcription factor, leads to developmental delay, intellectual disability, autism spectrum disorder, speech delay, and dysmorphic features. Most of the reported FOXP1 mutations occur on the C-terminus of the protein and cluster around to the forkhead domain. All reported FOXP1 pathogenic variants result in abnormal cellular localization and loss of transcriptional repression activity of the protein product. Here we present three patients with the same FOXP1 mutation, c.1574G\u3eA (p.R525Q), that results in the characteristic loss of transcription repression activity. This mutation, however, represents the first reported FOXP1 mutation that does not result in cytoplasmic or nuclear aggregation of the protein but maintains normal nuclear localization

Impact of Scotland’s comprehensive, smoke-free legislation on stroke

<p>Background: Previous studies have reported a reduction in acute coronary events following smoke-free legislation. Evidence is lacking on whether stroke is also reduced. The aim was to determine whether the incidence of stroke, overalland by sub-type, fell following introduction of smoke-free legislation across Scotland on 26 March 2006.</p> <p>Methods and Findings: A negative binomial regression model was used to determine whether the introduction of smokefree legislation resulted in a step and/or slope change in stroke incidence. The model was adjusted for age-group, sex, socioeconomic deprivation quintile, urban/rural residence and month. Interaction tests were also performed. Routine hospital administrative data and death certificates were used to identify all hospital admissions and pre-hospital deaths due to stroke (ICD10 codes I61, I63 and I64) in Scotland between 2000 and 2010 inclusive. Prior to the legislation, rates of all stroke, intracerebral haemorrhage and unspecified stroke were decreasing, whilst cerebral infarction was increasing at 0.97% per annum. Following the legislation, there was a dramatic fall in cerebral infarctions that persisted for around 20 months. No visible effect was observed for other types of stroke. The model confirmed an 8.90% (95% CI 4.85, 12.77, p,0.001) stepwise reduction in cerebral infarction at the time the legislation was implemented, after adjustment for potential cofounders.</p> <p>Conclusions: Following introduction of national, comprehensive smoke-free legislation there was a selective reduction in cerebral infarction that was not apparent in other types of stroke.</p&gt

A multi-level system quality improvement intervention to reduce racial disparities in hypertension care and control: study protocol.

PMC3680084Abstract BACKGROUND: Racial disparities in blood pressure control have been well documented in the United States. Research suggests that many factors contribute to this disparity, including barriers to care at patient, clinician, healthcare system, and community levels. To date, few interventions aimed at reducing hypertension disparities have addressed factors at all of these levels. This paper describes the design of Project ReD CHiP (Reducing Disparities and Controlling Hypertension in Primary Care), a multi-level system quality improvement project. By intervening on multiple levels, this project aims to reduce disparities in blood pressure control and improve guideline concordant hypertension care. METHODS: Using a pragmatic trial design, we are implementing three complementary multi-level interventions designed to improve blood pressure measurement, provide patient care management services and offer expanded provider education resources in six primary care clinics in Baltimore, Maryland. We are staggering the introduction of the interventions and will use Statistical Process Control (SPC) charting to determine if there are changes in outcomes at each clinic after implementation of each intervention. The main hypothesis is that each intervention will have an additive effect on improvements in guideline concordant care and reductions in hypertension disparities, but the combination of all three interventions will result in the greatest impact, followed by blood pressure measurement with care management support, blood pressure measurement with provider education, and blood pressure measurement only. This study also examines how organizational functioning and cultural competence affect the success of the interventions. DISCUSSION: As a quality improvement project, Project ReD CHiP employs a novel study design that specifically targets multi-level factors known to contribute to hypertension disparities. To facilitate its implementation and improve its sustainability, we have incorporated stakeholder input and tailored components of the interventions to meet the specific needs of the involved clinics and communities. Results from this study will provide knowledge about how integrated multi-level interventions can improve hypertension care and reduce disparities. TRIAL REGISTRATION: ClinicalTrials.gov NCT01566864.JH Libraries Open Access Fun

Somatic diversification of variable lymphocyte receptors in the agnathan sea lamprey

Although jawless vertebrates are apparently capable of adaptive immune responses, they have not been found to possess the recombinatorial antigen receptors shared by all jawed vertebrates. Our search for the phylogenetic roots of adaptive immunity in the lamprey has instead identified a new type of variable lymphocyte receptors (VLRs) composed of highly diverse leucine-rich repeats (LRR) sandwiched between amino- and carboxy-terminal LRRs. An invariant stalk region tethers the VLRs to the cell surface by means of a glycosyl-phosphatidyl-inositol anchor. To generate rearranged VLR genes of the diversity necessary for an anticipatory immune system, the single lamprey VLR locus contains a large bank of diverse LRR cassettes, available for insertion into an incomplete germline VLR gene. Individual lymphocytes express a uniquely rearranged VLR gene in monoallelic fashion. Different evolutionary strategies were thus used to generate highly diverse lymphocyte receptors through rearrangement of LRR modules in agnathans ( jawless fish) and of immunoglobulin gene segments in gnathostomes ( jawed vertebrates).Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/62870/1/nature02740.pd

Public health in community pharmacy: a systematic review of pharmacist and consumer views

BACKGROUND The increasing involvement of pharmacists in public health will require changes in the behaviour of both pharmacists and the general public. A great deal of research has shown that attitudes and beliefs are important determinants of behaviour. This review aims to examine the beliefs and attitudes of pharmacists and consumers towards pharmaceutical public health in order to inform how best to support and improve this service. METHODS Five electronic databases were searched for articles published in English between 2001 and 2010. Titles and abstracts were screened by one researcher according to the inclusion criteria. Papers were included if they assessed pharmacy staff or consumer attitudes towards pharmaceutical public health. Full papers identified for inclusion were assessed by a second researcher and data were extracted by one researcher. RESULTS From the 5628 papers identified, 63 studies in 67 papers were included. Pharmacy staff: Most pharmacists viewed public health services as important and part of their role but secondary to medicine related roles. Pharmacists' confidence in providing public health services was on the whole average to low. Time was consistently identified as a barrier to providing public health services. Lack of an adequate counselling space, lack of demand and expectation of a negative reaction from customers were also reported by some pharmacists as barriers. A need for further training was identified in relation to a number of public health services. Consumers: Most pharmacy users had never been offered public health services by their pharmacist and did not expect to be offered. Consumers viewed pharmacists as appropriate providers of public health advice but had mixed views on the pharmacists' ability to do this. Satisfaction was found to be high in those that had experienced pharmaceutical public health. CONCLUSIONS There has been little change in customer and pharmacist attitudes since reviews conducted nearly 10 years previously. In order to improve the public health services provided in community pharmacy, training must aim to increase pharmacists' confidence in providing these services. Confident, well trained pharmacists should be able to offer public health service more proactively which is likely to have a positive impact on customer attitudes and health

Rugged Single Domain Antibody Detection Elements for Bacillus anthracis Spores and Vegetative Cells

Significant efforts to develop both laboratory and field-based detection assays for an array of potential biological threats started well before the anthrax attacks of 2001 and have continued with renewed urgency following. While numerous assays and methods have been explored that are suitable for laboratory utilization, detection in the field is often complicated by requirements for functionality in austere environments, where limited cold-chain facilities exist. In an effort to overcome these assay limitations for Bacillus anthracis, one of the most recognizable threats, a series of single domain antibodies (sdAbs) were isolated from a phage display library prepared from immunized llamas. Characterization of target specificity, affinity, and thermal stability was conducted for six sdAb families isolated from rounds of selection against the bacterial spore. The protein target for all six sdAb families was determined to be the S-layer protein EA1, which is present in both vegetative cells and bacterial spores. All of the sdAbs examined exhibited a high degree of specificity for the target bacterium and its spore, with affinities in the nanomolar range, and the ability to refold into functional antigen-binding molecules following several rounds of thermal denaturation and refolding. This research demonstrates the capabilities of these sdAbs and their potential for integration into current and developing assays and biosensors

Differential Expression of Iron Acquisition Genes by Brucella melitensis and Brucella canis during Macrophage Infection

Brucella spp. cause chronic zoonotic disease often affecting individuals and animals in impoverished economic or public health conditions; however, these bacteria do not have obvious virulence factors. Restriction of iron availability to pathogens is an effective strategy of host defense. For brucellae, virulence depends on the ability to survive and replicate within the host cell where iron is an essential nutrient for the growth and survival of both mammalian and bacterial cells. Iron is a particularly scarce nutrient for bacteria with an intracellular lifestyle. Brucella melitensis and Brucella canis share ∼99% of their genomes but differ in intracellular lifestyles. To identify differences, gene transcription of these two pathogens was examined during infection of murine macrophages and compared to broth grown bacteria. Transcriptome analysis of B. melitensis and B. canis revealed differences of genes involved in iron transport. Gene transcription of the TonB, enterobactin, and ferric anguibactin transport systems was increased in B. canis but not B. melitensis during infection of macrophages. The data suggest differences in iron requirements that may contribute to differences observed in the lifestyles of these closely related pathogens. The initial importance of iron for B. canis but not for B. melitensis helps elucidate differing intracellular survival strategies for two closely related bacteria and provides insight for controlling these pathogens