Individual Level Injection History: A Lack of Association with HIV Incidence in Rural Zimbabwe

BACKGROUND: It has recently been argued that unsafe medical injections are a major transmission route of HIV infection in the generalised epidemics of sub-Saharan Africa. METHODS AND FINDINGS: We have analysed the pattern of injections in relation to HIV incidence in a population cohort in Manicaland in a rural area of Zimbabwe. In Poisson regression models, injections were not found to be associated with HIV in males (rate ratio = 0.33; 95% confidence interval: 0.07 to 1.46) or females (rate ratio = 1.04; 95% confidence interval: 0.59 to 1.85). CONCLUSION: It is important that unsafe medical injections can be confidently excluded as a major source of HIV infection. In rural Zimbabwe the evidence is that they can

Bottom up ethics - neuroenhancement in education and employment

Neuroenhancement involves the use of neurotechnologies to improve cognitive, affective or behavioural functioning, where these are not judged to be clinically impaired. Questions about enhancement have become one of the key topics of neuroethics over the past decade. The current study draws on in-depth public engagement activities in ten European countries giving a bottom-up perspective on the ethics and desirability of enhancement. This informed the design of an online contrastive vignette experiment that was administered to representative samples of 1000 respondents in the ten countries and the United States. The experiment investigated how the gender of the protagonist, his or her level of performance, the efficacy of the enhancer and the mode of enhancement affected support for neuroenhancement in both educational and employment contexts. Of these, higher efficacy and lower performance were found to increase willingness to support enhancement. A series of commonly articulated claims about the individual and societal dimensions of neuroenhancement were derived from the public engagement activities. Underlying these claims, multivariate analysis identified two social values. The Societal/Protective highlights counter normative consequences and opposes the use enhancers. The Individual/Proactionary highlights opportunities and supports use. For most respondents these values are not mutually exclusive. This suggests that for many neuroenhancement is viewed simultaneously as a source of both promise and concern

Low wintertime vitamin D levels in a sample of healthy young adults of diverse ancestry living in the Toronto area: associations with vitamin D intake and skin pigmentation

<p>Abstract</p> <p>Background</p> <p>Vitamin D plays a critical role in bone metabolism and many cellular and immunological processes. Recent research indicates that concentrations of serum 25-hydroxyvitamin D [25(OH)D], the main indicator of vitamin D status, should be in excess of 75 nmol/L. Low levels of 25(OH)D have been associated with several chronic and infectious diseases. Previous studies have reported that many otherwise healthy adults of European ancestry living in Canada have low vitamin D concentrations during the wintertime. However, those of non-European ancestry are at a higher risk of having low vitamin D levels. The main goal of this study was to examine the vitamin D status and vitamin D intake of young Canadian adults of diverse ancestry during the winter months.</p> <p>Methods</p> <p>One hundred and seven (107) healthy young adults self-reporting their ancestry were recruited for this study. Each participant was tested for serum 25(OH)D concentrations and related biochemistry, skin pigmentation indices and basic anthropometric measures. A seven-day food diary was used to assess their vitamin D intake. An ANOVA was used to test for significant differences in the variables among groups of different ancestry. Linear regression was employed to assess the impact of relevant variables on serum 25(OH)D concentrations.</p> <p>Results</p> <p>More than 93% of the total sample had concentrations below 75 nmol/L. Almost three-quarters of the subjects had concentrations below 50 nmol/L. There were significant differences in serum 25(OH)D levels (p < 0.001) and vitamin D intake (p = 0.034) between population groups. Only the European group had a mean vitamin D intake exceeding the current Recommended Adequate Intake (RAI = 200 IU/day). Total vitamin D intake (from diet and supplements) was significantly associated with 25(OH)D levels (p < 0.001). Skin pigmentation, assessed by measuring skin melanin content, showed an inverse relationship with serum 25(OH)D (p = 0.033).</p> <p>Conclusion</p> <p>We observe that low vitamin D levels are more prevalent in our sample of young healthy adults than previously reported, particularly amongst those of non-European ancestry. Major factors influencing 25(OH)D levels were vitamin D intake and skin pigmentation. These data suggest a need to increase vitamin D intake either through improved fortification and/or supplementation.</p

Emotion Coregulation in Mother-Child Dyads: A Dynamic Systems Analysis of Children with and without Autism Spectrum Disorder

Few studies have investigated patterns of emotion coregulation in families of children with Autism Spectrum Disorder (ASD) or contrasted the ways in which their emotion coregulation patterns differ from families of typically developing (TD) children. To address this gap, we used a dynamic systems approach to compare flexible structure and emotional content of coregulation between mothers and children (3-7&nbsp;years) with ASD (n&nbsp;=&nbsp;47) and TD children (n&nbsp;=&nbsp;26). Mother-child play interactions in the home were videotaped and emotion-engagement states were coded in micro-level 5-s intervals based on behavioral and affective expressions. Analyses indicated that mother-child dyads in the ASD group spent more time than dyads in the TD group in mismatched emotion-engagement states (e.g., child negative/mother positive), and children with ASD spent more time than TD children engaged exclusively with objects. Mother-child dyads in the TD group stayed longer in mutual positive engagement states. Compared to dyads in the TD group, mother-child dyads in the ASD group exhibited greater flexibility (i.e., a wider range of emotional-engagement states, more frequent changes in states, and less time in each state). These findings suggest that mothers and their children with ASD do not sustain dyadic positive engagement patterns in a low-stress environment. Findings confirmed the preference of children with ASD for objects over social partners, even when they are at home with their mothers, and elucidated a challenging mother-child interactional style. Results have implications for mother-child interventions aimed at regulating negative emotional states and sustaining positive ones in families raising children with ASD

Emotion Coregulation in Mother-Child Dyads: A Dynamic Systems Analysis of Children with and without Autism Spectrum Disorder.

Few studies have investigated patterns of emotion coregulation in families of children with Autism Spectrum Disorder (ASD) or contrasted the ways in which their emotion coregulation patterns differ from families of typically developing (TD) children. To address this gap, we used a dynamic systems approach to compare flexible structure and emotional content of coregulation between mothers and children (3-7&nbsp;years) with ASD (n&nbsp;=&nbsp;47) and TD children (n&nbsp;=&nbsp;26). Mother-child play interactions in the home were videotaped and emotion-engagement states were coded in micro-level 5-s intervals based on behavioral and affective expressions. Analyses indicated that mother-child dyads in the ASD group spent more time than dyads in the TD group in mismatched emotion-engagement states (e.g., child negative/mother positive), and children with ASD spent more time than TD children engaged exclusively with objects. Mother-child dyads in the TD group stayed longer in mutual positive engagement states. Compared to dyads in the TD group, mother-child dyads in the ASD group exhibited greater flexibility (i.e., a wider range of emotional-engagement states, more frequent changes in states, and less time in each state). These findings suggest that mothers and their children with ASD do not sustain dyadic positive engagement patterns in a low-stress environment. Findings confirmed the preference of children with ASD for objects over social partners, even when they are at home with their mothers, and elucidated a challenging mother-child interactional style. Results have implications for mother-child interventions aimed at regulating negative emotional states and sustaining positive ones in families raising children with ASD

Combined Transcriptome and Proteome Analysis of Immortalized Human Keratinocytes Expressing Human Papillomavirus 16 (HPV16) Oncogenes Reveals Novel Key Factors and Networks in HPV-Induced Carcinogenesis

Human papillomavirus (HPV)-associated cancers still remain a big health problem, especially in developing countries, despite the availability of prophylactic vaccines. Although HPV oncogenes have been intensively investigated for decades, a study applying recent advances in RNA-Seq and quantitative proteomic approaches to a precancerous model system with well-defined HPV oncogene expression alongside HPV-negative parental cells has been missing until now. Here, combined omics analyses reveal global changes caused by the viral oncogenes in a less biased way and allow the identification of novel factors and key cellular networks potentially promoting malignant transformation. In addition, this system also provides a basis for mechanistic research on novel key factors regulated by HPV oncogenes, especially those that are confirmed in vivo in cervical cancer as well as in head and neck cancer patient samples from TCGA data sets.Although the role of high-risk human papillomaviruses (hrHPVs) as etiological agents in cancer development has been intensively studied during the last decades, there is still the necessity of understanding the impact of the HPV E6 and E7 oncogenes on host cells, ultimately leading to malignant transformation. Here, we used newly established immortalized human keratinocytes with a well-defined HPV16 E6E7 expression cassette to get a more complete and less biased overview of global changes induced by HPV16 by employing transcriptome sequencing (RNA-Seq) and stable isotope labeling by amino acids in cell culture (SILAC). This is the first study combining transcriptome and proteome data to characterize the impact of HPV oncogenes in human keratinocytes in comparison with their virus-negative counterparts. To enhance the informative value and accuracy of the RNA-Seq data, four different bioinformatic workflows were used. We identified potential novel upstream regulators (e.g., CNOT7, SPDEF, MITF, and PAX5) controlling distinct clusters of genes within the HPV-host cell network as well as distinct factors (e.g., CPPED1, LCP1, and TAGLN) with essential functions in cancer. Validated results in this study were compared to data sets from The Cancer Genome Atlas (TCGA), demonstrating that several identified factors were also differentially expressed in cervical squamous cell carcinoma and endocervical adenocarcinoma (CESC) and HPV-positive head and neck squamous cell carcinomas (HNSCs). This highly integrative approach allows the identification of novel HPV-induced cellular changes that are also reflected in cancer patients, providing a promising omics data set for future studies in both basic and translational research

Selective BMP-9 Inhibition Partially Protects Against Experimental Pulmonary Hypertension

International audienceRATIONALE:Although many familial cases of pulmonary arterial hypertension (PAH) exhibit an autosomal dominant mode of inheritance with the majority having mutations in essential constituents of the bone morphogenetic protein (BMP) signaling, the specific contribution of the long-term loss of signal transduction triggered by the type 2 BMP receptor (BMPR2) remains poorly characterized.OBJECTIVE:To investigate the role of BMP9, the main ligand of ALK1/BMPR2 heterocomplexes, in pulmonary hypertension (PH).METHODS AND RESULTS:The absence of BMP9 in Bmp9-/- mice and its inhibition in C57BL/6 mice using neutralizing anti-BMP9 antibodies substantially prevent against chronic hypoxia induced PH judged by right ventricular systolic pressure (RVSP) measurement, right ventricular hypertrophy, and pulmonary distal arterial muscularization. In agreement with these observations, we found that the BMP9/BMP10 ligand trap ALK1ECD administered in monocrotaline (MCT) or Sugen/hypoxia (SuHx) rats substantially attenuate proliferation of pulmonary vascular cells, inflammatory cell infiltration and regresses established PH in rats. Our data obtained in human pulmonary endothelial cells derived from controls and PAH patients indicate that BMP9 can affect the balance between endothelin-1, apelin and adrenomedullin. We reproduced these in vitro observations in mice chronically exposed to hypoxia, with Bmp9-/- mice exhibiting lower mRNA levels of the vasoconstrictor peptide endothelin (ET)-1 and higher levels of the two potent vasodilator factors apelin and adrenomedullin (ADM) compared with Bmp9 +/+ littermates.CONCLUSIONS:Taken together, our data indicate that the loss of BMP9, by deletion or inhibition, has beneficial effects against PH onset and progression