1,132 research outputs found

    Risky Sex and HIV Acquisition Among HIV Serodiscordant Couples in Zambia, 2002-2012: What Does Alcohol Have To Do With It?

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    In this paper we evaluate the effects of heavy alcohol consumption on sexual behavior, HIV acquisition, and antiretroviral treatment (ART) initiation in a longitudinal open cohort of 1929 serodiscordant couples in Lusaka, Zambia from 2002 to 2012. We evaluated factors associated with baseline heavy alcohol consumption and its association with condomless sex with the study partner, sex outside of the partnership, and ART initiation using multivariable logistic regression. We estimated the effect of alcohol consumption on HIV acquisition using multivariable Cox models. Baseline factors significantly associated with women's heavy drinking (drunk weekly or more in 12-months before enrollment) included woman's older age (adjusted prevalence odds ratio [aPOR] = 1.04), partner heavy drinking (aPOR = 3.93), and being HIV-infected (aPOR = 2.03). Heavy drinking among men was associated with less age disparity with partner (aPOR per year disparity = 0.97) and partner heavy drinking (aPOR = 1.63). Men's being drunk daily (aOR = 1.18), women's being drunk less than monthly (aOR = 1.39) vs. never drunk and being in a male HIV-negative and female HIV-positive union (aOR = 1.45) were associated with condomless sex. Heavy alcohol use was associated with having 1 or more outside sex partners among men (aOR drunk daily = 1.91, drunk weekly = 1.32, drunk monthly = 2.03 vs. never), and women (aOR drunk monthly = 2.75 vs. never). Being drunk weekly or more increased men's risk of HIV acquisition (adjusted hazard ratio [aHR] = 1.72). Men and women being drunk weekly or more was associated (p < 0.1) with women's seroconversion (aHR = 1.42 and aHR = 3.71 respectively). HIV-positive women who were drunk monthly or more had lower odds of initiating ART (aOR = 0.83; 95% CI = 0.70-0.99) adjusting for age, months since baseline and previous pregnancies. Individuals in HIV-serodiscordant couples who reported heavy drinking had more outside sex partnerships and condomless sex with their study partner and were more likely to acquire HIV. HIV-positive women had lower odds of initiating ART if they were heavy drinkers

    A Three-Dimensional Computational Model of Collagen Network Mechanics

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    Extracellular matrix (ECM) strongly influences cellular behaviors, including cell proliferation, adhesion, and particularly migration. In cancer, the rigidity of the stromal collagen environment is thought to control tumor aggressiveness, and collagen alignment has been linked to tumor cell invasion. While the mechanical properties of collagen at both the single fiber scale and the bulk gel scale are quite well studied, how the fiber network responds to local stress or deformation, both structurally and mechanically, is poorly understood. This intermediate scale knowledge is important to understanding cell- ECM interactions and is the focus of this study. We have developed a three-dimensional elastic collagen fiber network model (bead-and-spring model) and studied fiber network behaviors for various biophysical conditions: collagen density, crosslinker strength, crosslinker density, and fiber orientation (random vs. prealigned). We found the best-fit crosslinker parameter values using shear simulation tests in a small strain region. Using this calibrated collagen model, we simulated both shear and tensile tests in a large linear strain region for different network geometry conditions. The results suggest that network geometry is a key determinant of the mechanical properties of the fiber network. We further demonstrated how the fiber network structure and mechanics evolves with a local formation, mimicking the effect of pulling by a pseudopod during cell migration. Our computational fiber network model is a step toward a full biomechanical model of cellular behaviors in various ECM conditions

    Active and covert infections of cricket Iridovirus and Acheta domesticus Densovirus in reared Gryllodes sigillatus crickets

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    Interest in developing food, feed, and other useful products from farmed insects has gained remarkable momentum in the past decade. Crickets are an especially popular group of farmed insects due to their nutritional quality, ease of rearing, and utility. However, production of crickets as an emerging commodity has been severely impacted by entomopathogenic infections, about which we know little. Here, we identified and characterized an unknown entomopathogen causing mass mortality in a lab-reared population of Gryllodes sigillatus crickets, a species used as an alternative to the popular Acheta domesticus due to its claimed tolerance to prevalent entomopathogenic viruses. Microdissection of sick and healthy crickets coupled with metagenomics-based identification and real-time qPCR viral quantification indicated high levels of cricket iridovirus (CrIV) in a symptomatic population, and evidence of covert CrIV infections in a healthy population. Our study also identified covert infections of Acheta domesticus densovirus (AdDNV) in both populations of G. sigillatus. These results add to the foundational research needed to better understand the pathology of mass-reared insects and ultimately develop the prevention, mitigation, and intervention strategies needed for economical production of insects as a commodity

    Theory of mind and social judgments in people at clinical high risk of psychosis

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    Social cognitive deficits are consistently reported in psychotic populations. Few studies have longitudinally investigated social cognition in clinical high-risk (CHR) populations

    Heart failure in women with hypertensive disorders of pregnancy: Insights from the cardiovascular disease in Norway project

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    Hypertensive disorders of pregnancy (HDP) have been associated with heart failure (HF). It is unknown whether concurrent pregnancy complications (small-for-gestational-age or preterm delivery) or recurrent HDP modify HDP-associated HF risk. In this cohort study, we included Norwegian women with a first birth between 1980 and 2004. Follow-up occurred through 2009. Cox models examined gestational hypertension and preeclampsia in the first pregnancy as predictors of a composite of HF-related hospitalization or HF-related death, with assessment of effect modification by concurrent small-for-gestational-age or preterm delivery. Additional models were stratified by final parity (1 versus ≥2 births) and tested associations with recurrent HDP. Among 508 422 women, 565 experienced incident HF over a median 11.8 years of follow-up. After multivariable adjustment, gestational hypertension in the first birth was not significantly associated with HF (hazard ratio, 1.41 [95% CI, 0.84–2.35], P=0.19), whereas preeclampsia was associated with a hazard ratio of 2.00 (95% CI, 1.50–2.68, P<0.001). Among women with HDP, risks were not modified by concurrent small-for-gestational-age or preterm delivery (Pinteraction=0.42). Largest hazards of HF were observed in women whose only lifetime birth was complicated by preeclampsia and women with recurrent preeclampsia. HF risks were similar after excluding women with coronary artery disease. In summary, women with preeclampsia, especially those with one lifetime birth and those with recurrent preeclampsia, experienced increased HF risk compared to women without HDP. Further research is needed to clarify causal mechanisms.acceptedVersio

    The International Scientific Association for Probiotics and Prebiotics (ISAPP) consensus statement on the definition and scope of synbiotics

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    In May 2019, the International Scientific Association for Probiotics and Prebiotics (ISAPP) convened a panel of nutritionists, physiologists and microbiologists to review the definition and scope of synbiotics. The panel updated the definition of a synbiotic to “a mixture comprising live microorganisms and substrate(s) selectively utilized by host microorganisms that confers a health benefit on the host”. The panel concluded that defining synbiotics as simply a mixture of probiotics and prebiotics could suppress the innovation of synbiotics that are designed to function cooperatively. Requiring that each component must meet the evidence and dose requirements for probiotics and prebiotics individually could also present an obstacle. Rather, the panel clarified that a complementary synbiotic, which has not been designed so that its component parts function cooperatively, must be composed of a probiotic plus a prebiotic, whereas a synergistic synbiotic does not need to be so. A synergistic synbiotic is a synbiotic for which the substrate is designed to be selectively utilized by the co-administered microorganisms. This Consensus Statement further explores the levels of evidence (existing and required), safety, effects upon targets and implications for stakeholders of the synbiotic concept

    Genome-wide assessment of antimicrobial tolerance in Yersinia pseudotuberculosis under ciprofloxacin stress.

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    Yersinia pseudotuberculosis is a Gram-negative bacterium capable of causing gastrointestinal infection and is closely related to the highly virulent plague bacillus Yersinia pestis. Infections by both species are currently treatable with antibiotics such as ciprofloxacin, a quinolone-class drug of major clinical importance in the treatment of many other infections. Our current understanding of the mechanism of action of ciprofloxacin is that it inhibits DNA replication by targeting DNA gyrase, and that resistance is primarily due to mutation of this target site, along with generic efflux and detoxification strategies. We utilized transposon-directed insertion site sequencing (TraDIS or TnSeq) to identify the non-essential chromosomal genes in Y. pseudotuberculosis that are required to tolerate sub-lethal concentrations of ciprofloxacin in vitro. As well as highlighting recognized antibiotic resistance genes, we provide evidence that multiple genes involved in regulating DNA replication and repair are central in enabling Y. pseudotuberculosis to tolerate the antibiotic, including DksA (yptb0734), a regulator of RNA polymerase, and Hda (yptb2792), an inhibitor of DNA replication initiation. We furthermore demonstrate that even at sub-lethal concentrations, ciprofloxacin causes severe cell-wall stress, requiring lipopolysaccharide lipid A, O-antigen and core biosynthesis genes to resist the sub-lethal effects of the antibiotic. It is evident that coping with the consequence(s) of antibiotic-induced stress requires the contribution of scores of genes that are not exclusively engaged in drug resistance

    The M33 Globular Cluster System with PAndAS Data: The Last Outer Halo Cluster?

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    We use CFHT/MegaCam data to search for outer halo star clusters in M33 as part of the Pan-Andromeda Archaeological Survey (PAndAS). This work extends previous studies out to a projected radius of 50 kpc and covers over 40 square degrees. We find only one new unambiguous star cluster in addition to the five previously known in the M33 outer halo (10 kpc <= r <= 50 kpc). Although we identify 2440 cluster candidates of various degrees of confidence from our objective image search procedure, almost all of these are likely background contaminants, mostly faint unresolved galaxies. We measure the luminosity, color and structural parameters of the new cluster in addition to the five previously-known outer halo clusters. At a projected radius of 22 kpc, the new cluster is slightly smaller, fainter and redder than all but one of the other outer halo clusters, and has g' ~ 19.9, (g'-i') ~ 0.6, concentration parameter c ~ 1.0, a core radius r_c ~ 3.5 pc, and a half-light radius r_h ~ 5.5 pc. For M33 to have so few outer halo clusters compared to M31 suggests either tidal stripping of M33's outer halo clusters by M31, or a very different, much calmer accretion history of M33.Comment: 37 pages, 9 figures. Accepted by the Astrophysical Journa

    Negative symptoms and impaired social functioning predict later psychosis in Latino youth at clinical high risk in the North American prodromal longitudinal studies consortium

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    AIM: Examining ethnically related variables in evaluating those at risk for psychosis is critical. This study investigated sociodemographic and clinical characteristics of Latino versus non-Latino clinical high-risk (CHR) subjects and healthy control (HC) subjects in the first North American Prodrome Longitudinal Study. METHODS: Fifty-six Latino CHR subjects were compared to 25 Latino HC and 423 non-Latino CHR subjects across clinical and demographic variables. Thirty-nine of the 56 CHR subjects completed at least one subsequent clinical evaluation over the 2.5-year period with 39% developing a psychotic illness. Characteristics of Latino CHR subjects who later converted to psychosis (‘converters’) were compared to those who did not (‘non-converters’). RESULTS: Latino CHR subjects were younger than non-Latino CHR subjects and had less education than Latino HC subjects and non-Latino CHR counterparts. Latino CHR converters had higher scores than Latino non-converters on the Structured Interview for Prodromal Syndromes total negative symptoms that were accounted for by decreased expression of emotion and personal hygiene/social attentiveness subsections. Latino CHR converters scored lower on the global functioning:social scale, indicating worse social functioning than Latino non-converters. CONCLUSION: Based on this sample, Latino CHR subjects may seek treatment earlier and have less education than non-Latino CHR subjects. Deficits in social functioning and impaired personal hygiene/social attentiveness among Latino CHR subjects predicted later psychosis and may represent important areas for future study. Larger sample sizes are needed to more thoroughly investigate the observed ethnic differences and risk factors for psychosis in Latino youth
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