A systematic review of school-based sexual health interventions to prevent STI/HIV in sub-Saharan Africa

Background The HIV/AIDS epidemic remains of global significance and there is a need to target (a) the adolescent age-groups in which most new infections occur; and (b) sub-Saharan Africa where the greatest burden of the epidemic lies. A focused systematic review of school-based sexual health interventions in sub-Saharan Africa to prevent HIV/AIDS and Sexually Transmitted Infections (STI) in this age group was therefore conducted. Methods Searches were conducted in Medline, Embase, Cinahl and PsychINFO according to agreed a priori criteria for studies published between 1986 and 2006. Further searches were conducted in UNAIDS and WHO (World Health Organization) websites, and 'Google'. Relevant journals were hand-searched and references cited in identified articles were followed up. Data extraction and quality assessment was carried out on studies selected for full text appraisal, and results were analysed and presented in narrative format. Results Some 1,020 possible titles and abstracts were found, 23 full text articles were critically appraised, and 12 articles (10 studies) reviewed, reflecting the paucity of published studies conducted relative to the magnitude of the HIV epidemic in sub-Saharan Africa. Knowledge and attitude-related outcomes were the most associated with statistically significant change. Behavioural intentions were more difficult to change and actual behaviour change was least likely to occur. Behaviour change in favour of abstinence and condom use appeared to be greatly influenced by pre-intervention sexual history. Conclusion There is a great need in sub-Saharan Africa for well-evaluated and effective school-based sexual health interventions

Two novel human cytomegalovirus NK cell evasion functions target MICA for lysosomal degradation

NKG2D plays a major role in controlling immune responses through the regulation of natural killer (NK) cells, αβ and γδ T-cell function. This activating receptor recognizes eight distinct ligands (the MHC Class I polypeptide-related sequences (MIC) A andB, and UL16-binding proteins (ULBP)1–6) induced by cellular stress to promote recognition cells perturbed by malignant transformation or microbial infection. Studies into human cytomegalovirus (HCMV) have aided both the identification and characterization of NKG2D ligands (NKG2DLs). HCMV immediate early (IE) gene up regulates NKGDLs, and we now describe the differential activation of ULBP2 and MICA/B by IE1 and IE2 respectively. Despite activation by IE functions, HCMV effectively suppressed cell surface expression of NKGDLs through both the early and late phases of infection. The immune evasion functions UL16, UL142, and microRNA(miR)-UL112 are known to target NKG2DLs. While infection with a UL16 deletion mutant caused the expected increase in MICB and ULBP2 cell surface expression, deletion of UL142 did not have a similar impact on its target, MICA. We therefore performed a systematic screen of the viral genome to search of addition functions that targeted MICA. US18 and US20 were identified as novel NK cell evasion functions capable of acting independently to promote MICA degradation by lysosomal degradation. The most dramatic effect on MICA expression was achieved when US18 and US20 acted in concert. US18 and US20 are the first members of the US12 gene family to have been assigned a function. The US12 family has 10 members encoded sequentially through US12–US21; a genetic arrangement, which is suggestive of an ‘accordion’ expansion of an ancestral gene in response to a selective pressure. This expansion must have be an ancient event as the whole family is conserved across simian cytomegaloviruses from old world monkeys. The evolutionary benefit bestowed by the combinatorial effect of US18 and US20 on MICA may have contributed to sustaining the US12 gene family

A mediation approach to understanding socio-economic inequalities in maternal health-seeking behaviours in Egypt.

BACKGROUND: The levels and origins of socio-economic inequalities in health-seeking behaviours in Egypt are poorly understood. This paper assesses the levels of health-seeking behaviours related to maternal care (antenatal care [ANC] and facility delivery) and their accumulation during pregnancy and childbirth. Secondly, it explores the mechanisms underlying the association between socio-economic position (SEP) and maternal health-seeking behaviours. Thirdly, it examines the effectiveness of targeting of free public ANC and delivery care. METHODS: Data from the 2008 Demographic and Health Survey were used to capture two latent constructs of SEP: individual socio-cultural capital and household-level economic capital. These variables were entered into an adjusted mediation model, predicting twelve dimensions of maternal health-seeking; including any ANC, private ANC, first ANC visit in first trimester, regular ANC (four or more visits during pregnancy), facility delivery, and private delivery. ANC and delivery care costs were examined separately by provider type (public or private). RESULTS: While 74.2% of women with a birth in the 5-year recall period obtained any ANC and 72.4% delivered in a facility, only 48.8% obtained the complete maternal care package (timely and regular facility-based ANC as well as facility delivery) for their most recent live birth. Both socio-cultural capital and economic capital were independently positively associated with receiving any ANC and delivering in a facility. The strongest direct effect of socio-cultural capital was seen in models predicting private provider use of both ANC and delivery. Despite substantial proportions of women using public providers reporting receipt of free care (ANC: 38%, delivery: 24%), this free-of-charge public care was not effectively targeted to women with lowest economic resources. CONCLUSIONS: Socio-cultural capital is the primary mechanism leading to inequalities in maternal health-seeking in Egypt. Future studies should therefore examine the objective and perceived quality of care from different types of providers. Improvements in the targeting of free public care could help reduce the existing SEP-based inequalities in maternal care coverage in the short term

National estimates for maternal mortality: an analysis based on the WHO systematic review of maternal mortality and morbidity

BACKGROUND: Despite the worldwide commitment to improving maternal health, measuring, monitoring and comparing maternal mortality estimates remain a challenge. Due to lack of data, international agencies have to rely on mathematical models to assess its global burden. In order to assist in mapping the burden of reproductive ill-health, we conducted a systematic review of incidence/prevalence of maternal mortality and morbidity. METHODS: We followed the standard methodology for systematic reviews. This manuscript presents nationally representative estimates of maternal mortality derived from the systematic review. Using regression models, relationships between study-specific and country-specific variables with the maternal mortality estimates are explored in order to assist further modelling to predict maternal mortality. RESULTS: Maternal mortality estimates included 141 countries and represent 78.1% of the live births worldwide. As expected, large variability between countries, and within regions and subregions, is identified. Analysis of variability according to study characteristics did not yield useful results given the high correlation with each other, with development status and region. A regression model including selected country-specific variables was able to explain 90% of the variability of the maternal mortality estimates. Among all country-specific variables selected for the analysis, three had the strongest relationships with maternal mortality: proportion of deliveries assisted by a skilled birth attendant, infant mortality rate and health expenditure per capita. CONCLUSION: With the exception of developed countries, variability of national maternal mortality estimates is large even within subregions. It seems more appropriate to study such variation through differentials in other national and subnational characteristics. Other than region, study of country-specific variables suggests infant mortality rate, skilled birth attendant at delivery and health expenditure per capita are key variables to predict maternal mortality at national level

The MRN complex is transcriptionally regulated by MYCN during neural cell proliferation to control replication stress

The MRE11/RAD50/NBS1 (MRN) complex is a major sensor of DNA double strand breaks, whose role in controlling faithful DNA replication and preventing replication stress is also emerging. Inactivation of the MRN complex invariably leads to developmental and/or degenerative neuronal defects, the pathogenesis of which still remains poorly understood. In particular, NBS1 gene mutations are associated with microcephaly and strongly impaired cerebellar development, both in humans and in the mouse model. These phenotypes strikingly overlap those induced by inactivation of MYCN, an essential promoter of the expansion of neuronal stem and progenitor cells, suggesting that MYCN and the MRN complex might be connected on a unique pathway essential for the safe expansion of neuronal cells. Here, we show that MYCN transcriptionally controls the expression of each component of the MRN complex. By genetic and pharmacological inhibition of the MRN complex in a MYCN overexpression model and in the more physiological context of the Hedgehog-dependent expansion of primary cerebellar granule progenitor cells, we also show that the MRN complex is required for MYCN-dependent proliferation. Indeed, its inhibition resulted in DNA damage, activation of a DNA damage response, and cell death in a MYCN- and replication-dependent manner. Our data indicate the MRN complex is essential to restrain MYCN-induced replication stress during neural cell proliferation and support the hypothesis that replication-born DNA damage is responsible for the neuronal defects associated with MRN dysfunctions.Cell Death and Differentiation advance online publication, 12 June 2015; doi:10.1038/cdd.2015.81

The diagnostic strength of the 24-h pad test for self-reported symptoms of urinary incontinence in pregnancy and after childbirth

The clinical impact of incontinence in pregnancy and after childbirth is growing because some studies report the efficacy of physiotherapy in pregnancy and because obstetric choices are supposed to have significant impact on post-reproductive urinary function (Goldberg et al. in Am J Obstet Gynecol 188:1447–1450, 2003). Thus, the need for objective measurement of urinary incontinence in pregnancy is growing. Data on pad testing in pregnancy are lacking. We assessed the clinical relevance of the 24-h pad test during pregnancy and after childbirth, compared with data on self-reported symptoms of urinary incontinence and visual analogue score. According to the receiver operating characteristic curve, the diagnostic value of pad testing for measuring (severity of) self-reported incontinence during pregnancy is not of clinical relevance. However, for the purposes of research, pad tests, combined with subjective/qualitative considerations, play a critical role in allowing comparisons across studies, quantifying the amount of urine loss and establishing a measure of severity

Generalized DNA Barcode Design Based on Hamming Codes

The diversity and scope of multiplex parallel sequencing applications is steadily increasing. Critically, multiplex parallel sequencing applications methods rely on the use of barcoded primers for sample identification, and the quality of the barcodes directly impacts the quality of the resulting sequence data. Inspection of the recent publications reveals a surprisingly variable quality of the barcodes employed. Some barcodes are made in a semi empirical fashion, without quantitative consideration of error correction or minimal distance properties. After systematic comparison of published barcode sets, including commercially distributed barcoded primers from Illumina and Epicentre, methods for improved, Hamming code-based sequences are suggested and illustrated. Hamming barcodes can be employed for DNA tag designs in many different ways while preserving minimal distance and error-correcting properties. In addition, Hamming barcodes remain flexible with regard to essential biological parameters such as sequence redundancy and GC content. Wider adoption of improved Hamming barcodes is encouraged in multiplex parallel sequencing applications

2019 international consensus on cardiopulmonary resuscitation and emergency cardiovascular care science with treatment recommendations : summary from the basic life support; advanced life support; pediatric life support; neonatal life support; education, implementation, and teams; and first aid task forces

The International Liaison Committee on Resuscitation has initiated a continuous review of new, peer-reviewed, published cardiopulmonary resuscitation science. This is the third annual summary of the International Liaison Committee on Resuscitation International Consensus on Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Science With Treatment Recommendations. It addresses the most recent published resuscitation evidence reviewed by International Liaison Committee on Resuscitation Task Force science experts. This summary addresses the role of cardiac arrest centers and dispatcher-assisted cardiopulmonary resuscitation, the role of extracorporeal cardiopulmonary resuscitation in adults and children, vasopressors in adults, advanced airway interventions in adults and children, targeted temperature management in children after cardiac arrest, initial oxygen concentration during resuscitation of newborns, and interventions for presyncope by first aid providers. Members from 6 International Liaison Committee on Resuscitation task forces have assessed, discussed, and debated the certainty of the evidence on the basis of the Grading of Recommendations, Assessment, Development, and Evaluation criteria, and their statements include consensus treatment recommendations. Insights into the deliberations of the task forces are provided in the Justification and Evidence to Decision Framework Highlights sections. The task forces also listed priority knowledge gaps for further research