1,773 research outputs found

    Oil cargo preference legislation : its potential impact on New England

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    21, [58] leaves : ill. ; 28 cm

    Effective Public Health Strategies to Optimize HIV Testing Services Among Men Ages 15 Years and Older in Kenya

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    Background: In Kenya, nearly 40,000 men living with HIV (MLHIV) remain undiagnosed, and there is a significant disparity in knowledge of HIV status between men (92%) and women (99%). HIV testing services (HTS) play a crucial role in diagnosing MLHIV and linking them to life-saving treatment and care. Purpose: to identify effective strategies to improve HTS uptake among men and strengthen the overall HIV program, considering COVID-19 and emerging public health threats. Methods: An adapted, explanatory sequential, mixed-methods two-phase design, was employed to assess various HIV testing modalities, including facility-based, community-based, and exposure-based testing, as well as HIV self-testing. Results: Key findings revealed that facility-based testing recorded the highest testing volume, with 3,628,537 men aged 15 and above undergoing testing, resulting in 115,752 newly diagnosed cases at a yield rate of 3.2%. Index testing accounted for 42.7% of newly diagnosed cases, outperforming Voluntary Counseling and Testing (VCT). Community-based testing had a low utilization rate, with only 3.0% of men tested, yielding 114,560 tests. Community Index testing was particularly successful, achieving a 37.1% testing rate, while mobile testing exhibited less effectiveness at 0.8%. The study also highlighted the potential of HIV self-testing (HIVST) in generating demand among men who test positive. COVID-19 impacted overall HIV testing volume, but HTS were resilient by employing prescribed modifications. Findings recommend expanding HIVST availability, improving data collection, and integrating HIVST into various testing modalities. Additionally, the study addressed the impact of the COVID-19 pandemic on testing services, emphasizing the need for adaptability and innovative approaches to maintain service continuity and prioritize high-risk populations. Conclusion: Overall, the recommendations encompass resource sustainability, comprehensive healthcare provider training, promotion of routine opt-out HIV testing in health facilities, and creation of male-friendly spaces. For community-based testing, recommendations focus on promoting community Index testing, strengthening home-based and mobile testing, integrating assisted and unassisted HIVST, and combining HIV testing with other health screenings through community health fairs. Amidst emerging threats, the program should adapt by ensuring safety measures, utilizing innovative approaches, and integrating HIV self-testing with other screenings, while strengthening monitoring and surveillance systems to respond effectively to disruptions in testing services.Doctor of Public Healt

    Integrating microRNA and mRNA expression profiles of neuronal progenitors to identify regulatory networks underlying the onset of cortical neurogenesis

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    <p>Abstract</p> <p>Background</p> <p>Cortical development is a complex process that includes sequential generation of neuronal progenitors, which proliferate and migrate to form the stratified layers of the developing cortex. To identify the individual microRNAs (miRNAs) and mRNAs that may regulate the genetic network guiding the earliest phase of cortical development, the expression profiles of rat neuronal progenitors obtained at embryonic day 11 (E11), E12 and E13 were analyzed.</p> <p>Results</p> <p>Neuronal progenitors were purified from telencephalic dissociates by a positive-selection strategy featuring surface labeling with tetanus-toxin and cholera-toxin followed by fluorescence-activated cell sorting. Microarray analyses revealed the fractions of miRNAs and mRNAs that were up-regulated or down-regulated in these neuronal progenitors at the beginning of cortical development. Nearly half of the dynamically expressed miRNAs were negatively correlated with the expression of their predicted target mRNAs.</p> <p>Conclusion</p> <p>These data support a regulatory role for miRNAs during the transition from neuronal progenitors into the earliest differentiating cortical neurons. In addition, by supplying a robust data set in which miRNA and mRNA profiles originate from the same purified cell type, this empirical study may facilitate the development of new algorithms to integrate various "-omics" data sets.</p

    Defoliation severity is positively related to soil solution nitrogen availability and negatively related to soil nitrogen concentrations following a multi-year invasive insect irruption

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    Understanding connections between ecosystem nitrogen (N) cycling and invasive insect defoliation could facilitate the prediction of disturbance impacts across a range of spatial scales. In this study we investigated relationships between ecosystem N cycling and tree defoliation during a recent 2015–18 irruption of invasive gypsy moth caterpillars (Lymantria dispar), which can cause tree stress and sometimes mortality following multiple years of defoliation. Nitrogen is a critical nutrient that limits the growth of caterpillars and plants in temperate forests. In this study, we assessed the associations among N concentrations, soil solution N availability and defoliation intensity by L. dispar at the scale of individual trees and forest plots. We measured leaf and soil N concentrations and soil solution inorganic N availability among individual red oak trees (Quercus rubra) in Amherst, MA and across a network of forest plots in Central Massachusetts. We combined these field data with estimated defoliation severity derived from Landsat imagery to assess relationships between plot-scale defoliation and ecosystem N cycling. We found that trees in soil with lower N concentrations experienced more herbivory than trees in soil with higher N concentrations. Additionally, forest plots with lower N soil were correlated with more severe L. dispar defoliation, which matched the tree-level relationship. The amount of inorganic N in soil solution was strongly positively correlated with defoliation intensity and the number of sequential years of defoliation. These results suggested that higher ecosystem N pools might promote the resistance of oak trees to L. dispar defoliation and that defoliation severity across multiple years is associated with a linear increase in soil solution inorganic N

    University students and the risk of HIV and other sexually transmitted infections in Uganda: the Crane survey.

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    Adolescents and young adults are at high risk of human immunodeficiency virus (HIV) infection in sub-Saharan Africa. Previous reports have found that university students in Africa comprise a sexually active population, although the prevalence of HIV or sexually transmitted infections (STI) has not been measured. We conducted a cross-sectional survey of students from five large universities in Kampala, Uganda, using respondent-driven sampling. We asked students to complete behavioral questionnaires and provide biological samples to test for HIV, Chlamydia trachomatis, Neisseria gonorrhoeae, Treponema pallidum, Trichomonas vaginalis, and bacterial vaginosis. We enrolled 649 students and obtained interpretable data from 640. Around 50% of the respondents were male, and the mean age was 22 years. An estimated 0.8% (95% CI 0.0-2.0) of male students had Chlamydia infection, approximately 4.3% (95% CI 2.0-7.0) had syphilis, 0.4% (95% CI 0.0-0.9) had HIV, and none had gonorrhea. An estimated 32.6% (95% CI 22.4-40.8) of women had bacterial vaginosis, 2.5% (95% CI 0.7-6.3) had Chlamydia infection, 1.7% (95% CI 0.5-3.6) had syphilis, 1.0% (95% CI 0.0-2.4) had gonorrhea, 0.9% (95% CI 0.0-4.2) had trichomoniasis, and 0.9% (95% CI 0.0-1.8) had HIV. We found no significant risk factors for HIV or other STI among males. We also found that not using a condom during the latest sexual intercourse was significantly associated with HIV infection, other STI, or bacterial vaginosis (OR 2.16; 95% 1.26-3.78) among females. We conclude that while university students are sexually active and there is substantial risk for syphilis, there is little evidence of substantially increased HIV risk among them

    Semiquantum thermodynamics of complex ferrimagnets

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    High-quality magnets such as yttrium iron garnet (YIG) are electrically insulating and very complex. By implementing a quantum thermostat into atomistic spin dynamics we compute YIG's key thermodynamic properties, viz., the magnon power spectrum and specific heat, for a large temperature range. The results differ (sometimes spectacularly) from simple models and classical statistics, but agree with available experimental data

    Cardiovascular disease in a cohort exposed to the 1940-45 Channel Islands occupation

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    BACKGROUND To clarify the nature of the relationship between food deprivation/undernutrition during pre- and postnatal development and cardiovascular disease (CVD) in later life, this study examined the relationship between birth weight (as a marker of prenatal nutrition) and the incidence of hospital admissions for CVD from 1997–2005 amongst 873 Guernsey islanders (born in 1923–1937), 225 of whom had been exposed to food deprivation as children, adolescents or young adults (i.e. postnatal undernutrition) during the 1940–45 German occupation of the Channel Islands, and 648 of whom had left or been evacuated from the islands before the occupation began. METHODS Three sets of Cox regression models were used to investigate (A) the relationship between birth weight and CVD, (B) the relationship between postnatal exposure to the occupation and CVD and (C) any interaction between birth weight, postnatal exposure to the occupation and CVD. These models also tested for any interactions between birth weight and sex, and postnatal exposure to the occupation and parish of residence at birth (as a marker of parish residence during the occupation and related variation in the severity of food deprivation). RESULTS The first set of models (A) found no relationship between birth weight and CVD even after adjustment for potential confounders (hazard ratio (HR) per kg increase in birth weight: 1.12; 95% confidence intervals (CI): 0.70 – 1.78), and there was no significant interaction between birth weight and sex (p = 0.60). The second set of models (B) found a significant relationship between postnatal exposure to the occupation and CVD after adjustment for potential confounders (HR for exposed vs. unexposed group: 2.52; 95% CI: 1.54 – 4.13), as well as a significant interaction between postnatal exposure to the occupation and parish of residence at birth (p = 0.01), such that those born in urban parishes (where food deprivation was worst) had a greater HR for CVD than those born in rural parishes. The third model (C) found no interaction between birth weight and exposure to the occupation (p = 0.43). CONCLUSION These findings suggest that the levels of postnatal undernutrition experienced by children, adolescents and young adults exposed to food deprivation during the 1940–45 occupation of the Channel Islands were a more important determinant of CVD in later life than the levels of prenatal undernutrition experienced in utero prior to the occupatio

    Crebinostat: A novel cognitive enhancer that inhibits histone deacetylase activity and modulates chromatin-mediated neuroplasticity

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    Long-term memory formation is known to be critically dependent upon de novo gene expression in the brain. As a consequence, pharmacological enhancement of the transcriptional processes mediating long-term memory formation provides a potential therapeutic strategy for cognitive disorders involving aberrant neuroplasticity. Here we focus on the identification and characterization of small molecule inhibitors of histone deacetylases (HDACs) as enhancers of CREB (cAMP response element-binding protein)-regulated transcription and modulators of chromatin-mediated neuroplasticity. Using a CREB reporter gene cell line, we screened a library of small molecules structurally related to known HDAC inhibitors leading to the identification of a probe we termed crebinostat that produced robust activation of CREB-mediated transcription. Further characterization of crebinostat revealed its potent inhibition of the deacetylase activity of recombinant class I HDACs 1, 2, 3, and class IIb HDAC6, with weaker inhibition of the class I HDAC8 and no significant inhibition of the class IIa HDACs 4, 5, 7, and 9. In cultured mouse primary neurons, crebinostat potently induced acetylation of both histone H3 and histone H4 as well as enhanced the expression of the CREB target gene Egr1 (early growth response 1). Using a hippocampus-dependent, contextual fear conditioning paradigm, mice systemically administered crebinostat for a ten day time period exhibited enhanced memory. To gain insight into the molecular mechanisms of memory enhancement by HDAC inhibitors, whole genome transcriptome profiling of cultured mouse primary neurons treated with crebinostat, combined with bioinformatic analyses of CREB-target genes, was performed revealing a highly connected protein–protein interaction network reflecting modules of genes important to synaptic structure and plasticity. Consistent with these findings, crebinostat treatment increased the density of synapsin-1 punctae along dendrites in cultured neurons. Finally, crebinostat treatment of cultured mouse primary neurons was found to upregulate Bdnf (brain-derived neurotrophic factor) and Grn (granulin) and downregulate Mapt (tau) gene expression—genes implicated in aging-related cognitive decline and cognitive disorders. Taken together, these results demonstrate that crebinostat provides a novel probe to modulate chromatin-mediated neuroplasticity and further suggests that pharmacological optimization of selective of HDAC inhibitors may provide an effective therapeutic approach for human cognitive disorders.National Institutes of Health (U.S.) (R01DA028301)National Institutes of Health (U.S.) (R01NS051874)Stanley Medical Research InstituteHoward Hughes Medical Institut
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