Specific phobia predicts psychopathology in young women

Contains fulltext : 90255.pdf (publisher's version ) (Closed access)Although specific phobia is characterized by an early age at onset and by high rates of comorbidity, few studies have examined comorbid relationships prospectively. The present study investigated the association between specific phobia and the risk of a broad range of psychopathology among young women in the community. Data came from the Dresden Predictor Study in which 1,538 German women (18-25 years) completed a diagnostic interview at two time points. Women with specific phobia had a twofold increase in odds of developing any anxiety disorder, generalized anxiety disorder, depression, and any somatoform disorder during 17 months, compared to women without specific phobia. Except for depression, these associations persisted after adjustment for all comorbid mental disorders. Specific phobia thus appears to be a risk factor for a variety of problems. The result further underpins the necessity for early intervention for specific phobia to prevent later mental health problems

Type I Gaucher disease with exophthalmos and pulmonary arteriovenous malformation

BACKGROUND: Gaucher disease type I, the non-neuropathic type, usually presents in adulthood with hepatosplenomegaly. We report here an adult with type I Gaucher disease presented with unusual and severe clinical manifestations. CASE PRESENTATION: Hepatosplenomegaly, bone crisis and fractures occurred at early childhood, and splenectomy was performed at the age of 5. Exophthalmos with increase in retrobulbar space was noted when the patient was 30. Cerezyme infusion started at the age of 32; but unfortunately, pulmonary arteriovenous malformation with dyspnea and hypoxemia was found two years later. Gene analysis revealed V375L/L444P mutations in the β-glucocerebrosidase gene. CONCLUSION: Although both eye and lung diseases have been associated with Gaucher disease, this is the first reported demonstration of exophthalmos and pulmonary arteriovenous malformation in the same patient. This case may therefore present an extremely severe and unusual form of type I Gaucher disease

Prenatal Detection of Aneuploidy and Imbalanced Chromosomal Arrangements by Massively Parallel Sequencing

Fetal chromosomal abnormalities are the most common reasons for invasive prenatal testing. Currently, G-band karyotyping and several molecular genetic methods have been established for diagnosis of chromosomal abnormalities. Although these testing methods are highly reliable, the major limitation remains restricted resolutions or can only achieve limited coverage on the human genome at one time. The massively parallel sequencing (MPS) technologies which can reach single base pair resolution allows detection of genome-wide intragenic deletions and duplication challenging karyotyping and microarrays as the tool for prenatal diagnosis. Here we reported a novel and robust MPS-based method to detect aneuploidy and imbalanced chromosomal arrangements in amniotic fluid (AF) samples. We sequenced 62 AF samples on Illumina GAIIx platform and with averagely 0.01× whole genome sequencing data we detected 13 samples with numerical chromosomal abnormalities by z-test. With up to 2× whole genome sequencing data we were able to detect microdeletion/microduplication (ranged from 1.4 Mb to 37.3 Mb of 5 samples from chorionic villus sampling (CVS) using SeqSeq algorithm. Our work demonstrated MPS is a robust and accurate approach to detect aneuploidy and imbalanced chromosomal arrangements in prenatal samples

Donation Crowdfunding : Principles and Donor Behaviour

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A population-based study of asthma, quality of life, and occupation among elderly Hispanic and non-Hispanic whites: a cross-sectional investigation

BACKGROUND: The U.S. population is aging and is expected to double by the year 2030. The current study evaluated the prevalence of asthma and its correlates in the elderly Hispanic and non-Hispanic white population. METHODS: Data from a sample of 3021 Hispanics and non-Hispanic White subjects, 65 years and older, interviewed as part of an ongoing cross-sectional study of the elderly in west Texas, were analyzed. The outcome variable was categorized into: no asthma (reference category), current asthma, and probable asthma. Polytomous logistic regression analysis was used to assess the relationship between the outcome variable and various socio-demographic measures, self-rated health, asthma symptoms, quality of life measures (SF-12), and various occupations. RESULTS: The estimated prevalence of current asthma and probable asthma were 6.3% (95%CI: 5.3–7.2) and 9.0% (95%CI: 7.8–10.1) respectively. The majority of subjects with current asthma (Mean SF-12 score 35.8, 95%CI: 34.2–37.4) or probable asthma (35.3, 34.0–36.6) had significantly worse physical health-related quality of life as compared to subjects without asthma (42.6, 42.1–43.1). In multiple logistic regression analyses, women had a 1.64 times greater odds of current asthma (95%CI: 1.12–2.38) as compared to men. Hay fever was a strong predictor of both current and probable asthma. The odds of current asthma were 1.78 times (95%CI: 1.24–2.55) greater among past smokers; whereas the odds of probable asthma were 2.73 times (95%CI: 1.77–4.21) greater among current smokers as compared to non-smokers. Similarly fair/poor self rated health and complaints of severe pain were independently associated with current and probable asthma. The odds of current and probable asthma were almost two fold greater for obesity. When stratified by gender, the odds were significantly greater among females (p-value for interaction term = 0.038). The odds of current asthma were significantly greater for farm-related occupations (adjusted OR = 2.09, 95%CI: 1.00–4.39); whereas the odds were significantly lower among those who reported teaching as their longest held occupation (adjusted OR = 0.36, 95%CI = 0.18–0.74). CONCLUSION: This study found that asthma is a common medical condition in the elderly and it significantly impacts quality of life and general health status. Results support adopting an integrated approach in identifying and controlling asthma in this population

Imaging of Zebrafish In Vivo with Second-Harmonic Generation Reveals Shortened Sarcomeres Associated with Myopathy Induced by Statin

We employed second-harmonic generation (SHG) imaging and the zebrafish model to investigate the myopathy caused by statin in vivo with emphasis on the altered microstructures of the muscle sarcomere, the fundamental contractile element of muscles. This approach derives an advantage of SHG imaging to observe the striated skeletal muscle of living zebrafish based on signals produced mainly from the thick myosin filament of sarcomeres without employing exogenous labels, and eliminates concern about the distortion of muscle structures caused by sample preparation in conventional histological examination. The treatment with statin caused a significantly shortened sarcomere relative to an untreated control (1.73±0.09 µm vs 1.91±0.08 µm, P<0.05) while the morphological integrity of the muscle fibers remained largely intact. Mechanistic tests indicated that this microstructural disorder was associated with the biosynthetic pathway of cholesterol, or, specifically, with the impaired production of mevalonate by statins. This microstructural disorder exhibited a strong dependence on both the dosage and the duration of treatment, indicating a possibility to assess the severity of muscle injury according to the altered length of the sarcomeres. In contrast to a conventional assessment of muscle injury using clinical biomarkers in blood, such as creatine kinase that is released from only disrupted myocytes, the ability to determine microstructural modification of sarcomeres allows diagnosis of muscle injury before an onset of conventional clinical symptoms. In light of the increasing prevalence of the incidence of muscle injuries caused by new therapies, our work consolidates the combined use of the zebrafish and SHG imaging as an effective and sensitive means to evaluate the safety profile of new therapeutic targets in vivo

Regulation of Septin Dynamics by the Saccharomyces cerevisiae Lysine Acetyltransferase NuA4

In the budding yeast Saccharomyces cerevisiae, the lysine acetyltransferase NuA4 has been linked to a host of cellular processes through the acetylation of histone and non-histone targets. To discover proteins regulated by NuA4-dependent acetylation, we performed genome-wide synthetic dosage lethal screens to identify genes whose overexpression is toxic to non-essential NuA4 deletion mutants. The resulting genetic network identified a novel link between NuA4 and septin proteins, a group of highly conserved GTP-binding proteins that function in cytokinesis. We show that acetyltransferase-deficient NuA4 mutants have defects in septin collar formation resulting in the development of elongated buds through the Swe1-dependent morphogenesis checkpoint. We have discovered multiple sites of acetylation on four of the five yeast mitotic septins, Cdc3, Cdc10, Cdc12 and Shs1, and determined that NuA4 can acetylate three of the four in vitro. In vivo we find that acetylation levels of both Shs1 and Cdc10 are reduced in a catalytically inactive esa1 mutant. Finally, we determine that cells expressing a Shs1 protein with decreased acetylation in vivo have defects in septin localization that are similar to those observed in NuA4 mutants. These findings provide the first evidence that yeast septin proteins are acetylated and that NuA4 impacts septin dynamics

Identification of BC005512 as a DNA Damage Responsive Murine Endogenous Retrovirus of GLN Family Involved in Cell Growth Regulation

Genotoxicity assessment is of great significance in drug safety evaluation, and microarray is a useful tool widely used to identify genotoxic stress responsive genes. In the present work, by using oligonucleotide microarray in an in vivo model, we identified an unknown gene BC005512 (abbreviated as BC, official full name: cDNA sequence BC005512), whose expression in mouse liver was specifically induced by seven well-known genotoxins (GTXs), but not by non-genotoxins (NGTXs). Bioinformatics revealed that BC was a member of the GLN family of murine endogenous retrovirus (ERV). However, the relationship to genotoxicity and the cellular function of GLN are largely unknown. Using NIH/3T3 cells as an in vitro model system and quantitative real-time PCR, BC expression was specifically induced by another seven GTXs, covering diverse genotoxicity mechanisms. Additionally, dose-response and linear regression analysis showed that expression level of BC in NIH/3T3 cells strongly correlated with DNA damage, measured using the alkaline comet assay,. While in p53 deficient L5178Y cells, GTXs could not induce BC expression. Further functional studies using RNA interference revealed that down-regulation of BC expression induced G1/S phase arrest, inhibited cell proliferation and thus suppressed cell growth in NIH/3T3 cells. Together, our results provide the first evidence that BC005512, a member from GLN family of murine ERV, was responsive to DNA damage and involved in cell growth regulation. These findings could be of great value in genotoxicity predictions and contribute to a deeper understanding of GLN biological functions