Congenital afibrinogenaemia caused by uniparental isodisomy of chromosome 4 containing a novel 15-kb deletion involving fibrinogen Aalpha-chain gene

Among rare inherited deficiencies of coagulation factors, congenital afibrinogenaemia is characterised by the lack of fibrinogen in plasma. In the last few years, several genetic defects underlying afibrinogenaemia (mostly point mutations) have been described in the fibrinogen gene cluster. In this study, the molecular basis responsible for afibrinogenaemia in a Thai proband was defined. Point mutation screening was accomplished by directly sequencing the three fibrinogen genes. The impossibility to amplify fibrinogen Aalpha-chain gene (FGA) exons 5 and 6 suggested the presence of a homozygous deletion. A specific long-range PCR assay enabled the identification of a novel 15-kb deletion, representing the largest afibrinogenaemia-causing deletion described so far. Direct sequencing of the deletion junction allowed mapping of the breakpoints in FGA intron 4 and in the intergenic region between Aalpha- and Bbeta-chain genes. Since the mutation was inherited only from the mother and nonpaternity was ruled out, a maternal uniparental disomy (UPD) was hypothesised. UPD test, carried out with markers covering the whole chromosome 4, revealed that maternal isodisomy was responsible for homozygosity of the 15-kb deletion in the proband. The apparently normal phenotype of the proband, except for afibrinogenaemia, suggests that UPD for chromosome 4 is clinically silent. This represents the first case of a documented complete isodisomy of chromosome 4 causing the phenotypic expression of a recessive disorder. In silico analyses of the regions surrounding the breakpoints suggested that the 15-kb deletion might have originated from an inappropriate repair of a double-strand break by the nonhomologous end joining mechanism.     

Etiology of Severe Acute Respiratory Infections,Bangladesh, 2017

In April 2017, surveillance detected a surge in severe acute respiratory infections (SARI) in Bangladesh. We collected specimens from SARI patients and asymptomatic controls for analysis with multipathogen diagnostic tests. Influenza A(H1N1)pdm09 was associated with the SARI epidemic, suggesting that introducing vaccines and empiric antiviral drugs could be beneficial.     

A community education monitoring system: methods from the Stanford Five-City Project, the Minnesota Heart Health Program and the Pawtucket Heart Health Program

Understanding the process of behavior change interventions is critical to achieving campaign effectiveness and successful program replication. The present article presents a community education monitoring system (CEMS) using data from the Stanford Five-City Project (FCP), the Minnesota Heart Health Program (MHHP) and the Pawtucket Heart Health Program (PHHP). CEMS records the number and type of intervention activities, outcome objectives, targets of change (individual, organizational or environmental), channel(s) of dissemination and proportion of programs funded by the community. These data illustrate (1) the application of theory for each project, (2) data-based program administration, (3) feedback for revising programs and (4) type of reach or 'dose' information obtained from intervention monitoring. Process evaluations such as CEMS provide critical links between field realities and evaluation outcomes. This type of evaluation develops standards for measuring program reach and allows comparisons with other programs. CEMS also illustrates how programs enact theory. Validation studies are critical to the continued successful use of CEMS. The first step, however, is to develop a uniform way of describing complex multichannel behavior change programs. CEMS in a refined form should prove invaluable to health promotion program planners whether in research or service settings.     

Program evaluation strategies for community-based health promotion programs: perspectives from the cardiovascular disease community research and demonstration studies

Community-based programs are being widely adopted in the struggle to prevent chronic disease. Program evaluation of community-based programs involves a particular set of problems stemming from the variety of activities being undertaken simultaneously, the multiple intermediate goals of the programs and the rapidity with which the programs evolve. An analysis of the experience of four large community-based cardiovascular disease research and demonstration studies (Stanford Five-City Project, Minnesota Heart Health Program, Pawtucket Heart Health Program and the German Cardiovascular Prevention Project) provides valuable models, methodologies and strategies for planning and conducting evaluations of public health programs or community studies. By comparing and combining their experiences, the four programs have identified eight categories of evaluation for community studies, including formative evaluation, quality assurance, assessment of delivered dose, assessment of received dose, component program impact, intermediate outcomes, community impact and cost analysis. This paper presents information on the strategies by which each of the four programs addressed these evaluation categories.     

PRELIMINARY RESEARCH ON ACUPUNCTURE EFFECTS IN IMMUNOLOGY

Experimental research has recently shown that acupuncture induces the formation of o-pioid-like peptides in animals.The role ofβ-endorphin in the mechanism of acupuncture is discussed:some authors maintain the hormonal hypothesis,others the role of neurotransmltters and,up to thepresent,no convincing evidence for either hypothesis has been demonstrated.In order to provide fur-ther evidence,we tested the β-endorphin levels and other parameters（VLP,lymphocyte subsets,NKcells and phagocyte activity of monocytes）in a group of 90 patients suffering from various painful dis-orders treated with acupuncture.Zusanli（ST 36）and Hegu（LI 4）acupoints were selected.A homo-geneous group of 30 subjects was used as control.Evaluation of the above parameters was made with3 series of blood tests;before treatment,30 minutes and 24 hours after acupuncture treatment.In theacupuncture group,the following results were achieved: a）A considerable increase in β-endorphin levels,which remained high even 24 hours afteracup     

Interaction between polycyclic aromatic hydrocarbons, crude oil and oil dispersants in the Salmonella mutagenesis assay

Mutagenicity assays were carried out in the Salmonella/microsometest, using five S. typhimurium his strains (TA1535, TA1537,TA1538, TA98 and TA100), both in the presence and absence ofpost-mitochondrial preparations from Aroclor-induced rat liversand suitable co-factors. Seven oil dispersants showed a widerange of toxicity towards the bacterial strains, without elicitingany mutagenic response at sub-lethal concentrations. One sampleof crude oil and its dimethylsulphoxide (DMSO) extract werealso negative, and no mutagenic effect could be detected bychecking mixtures of crude oil with each of the seven dispersantstested. Two polycyclic aromatic hydrocarbons, benzo(a)pyrene(BP) and benz(a) anthracene (BA), which are generally consideredto be the most documented carcinogenic components of crude oil,were mutagenic with a frameshift mechanism, requiring metabolicactivation. BP mutagenicity was not affected by oil dispersantsnor by seawater. Conversely, the mutagenicity of BP DMSO-solutionswas abolished in the presence either of whole crude oil, ofits DMSO extract, or of crude oil/dispersant mixtures. Theselosses of mutagenicity could be mainly ascribed to a mechanicaltrapping of BP by oil components.     

A comparison of participants and nonparticipants in a worksite cholesterol screening

PURPOSE. The purpose of this study is to determine if worksite cholesterol screening reaches only those who are already aware of their cholesterol and interested in lifestyle modification. DESIGN. A voluntary worksite cholesterol screening was conducted followed by a survey of a random sample of nonparticipants. SETTING. A large university worksite was the setting for this study. SUBJECTS. Out of 9,137 university employees, 1,583 attended the voluntary screening, and a random sample of nonparticipants was obtained (n = 154), of which 87% (n = 138) responded. MEASURES. Subjects completed a questionnaire on health behaviors, perceived risk, self-efficacy for diet change, and attention to media messages. A capillary blood cholesterol level was also taken. RESULTS. Nonparticipants were more likely to be male (64% versus 39%) and smokers (17% versus 9%), more likely to exercise, to have had a prior cholesterol measurement (64% versus 49%), and to "know" their cholesterol value (56% versus 26%). The two groups were otherwise similar. Over half (51%) of the participants were receiving their first cholesterol measurement. These subjects were younger, less educated, had less perceived risk, were less attentive to media messages, and more likely to be from a minority group than those individuals who had prior measurements. DISCUSSION. These findings suggest that worksite cholesterol screening does not only reach those already aware of their cholesterols, but also can reach some persons not previously screened or concerned.     

Normal values for metacarpal and phalangeal lengths in Nigerian children

Metacarpal and phalangeal lengths were measured on 1290 hand radiographs of Nigerian children, aged 3–16 years. The radiographs were obtained during a combined cross-sectional and longitudinal study of growth and development. There is a linear increase in tubular bone length with age in both sexes. The girls have higher values for all the bones up to the age of 13 years when the boys overtake them. Comparison of our data with those from North American children shows that the values amongst Nigerian children are higher than White, Black American and Mexican American children. Of particular note is the difference between Black American and Nigerian figures. It is postulated that the decreased metacarpophalangeal lengths in Black Americans compared with Nigerians may be due to gene dilution.     

De novo microduplication of the FMR1 gene in a patient with developmental delay,epilepsy and hyperactivity

Loss-of-function due to expansion of a CGG repeat located in the 5''UTR of the FMR1 gene is the most frequent cause of fragile X syndrome. Less than 1% of individuals with fragile X syndrome have been reported to have a partial or full deletion or point mutation of the FMR1 gene. However, whether a copy number gain of the FMR1 gene could result in certain clinical phenotypes has not been fully investigated. Here, we report the case of a child who presented with developmental delay starting at 9 months of age, fine motor and speech delay, progressive seizures since 18 months of age and hyperactivity. Molecular workup identified a de novo microduplication in the Xq27.3 region, including the FMR1 gene and the ASFMR1 gene. The expression level of the FMR1 gene in peripheral blood did not differ from that of the controls. In addition, an inherited 363-kb duplication on the chromosome 1q44 region and an inherited deletion of 168 kb on the chromosome 4p15.31 region were detected. It is not clear whether these inherited copy number variations (CNVs) also have a modifying role in the clinical phenotype of this patient.