Cellular O-Glycome Reporter/Amplification to explore O-glycans of living cells

Protein O-glycosylation has key roles in many biological processes, but the repertoire of O-glycans synthesized by cells is difficult to determine. Here we describe an approach termed Cellular O-Glycome Reporter/Amplification (CORA), a sensitive method used to amplify and profile mucin-type O-glycans synthesized by living cells. Cells convert added peracetylated benzyl-α-N-acetylgalactosamine to a large variety of modified O-glycan derivatives that are secreted from cells, allowing for easy purification for analysis by HPLC and mass spectrometry (MS). Relative to conventional O-glycan analyses, CORA resulted in an ∼100-1,000-fold increase in sensitivity and identified a more complex repertoire of O-glycans in more than a dozen cell types from Homo sapiens and Mus musculus. Furthermore, when coupled with computational modeling, CORA can be used for predictions about the diversity of the human O-glycome and offers new opportunities to identify novel glycan biomarkers for human diseases

Utilization of services provided by village based ethnic minority midwives in mountainous villages of Vietnam

Introduction: Since 2011, the Vietnam’s Ministry of Health implemented the ethnic minority midwives (EMMs) scheme in order to increase the utilization of maternal health services by women from ethnic minorities and those living in hard-to-reach mountainous areas. This paper analyzes the utilization of antenatal, delivery, and postpartum care provided by EMMs and reports the key determinants of utilization of EMM services as perceived by service users. Methods: A structured questionnaire was administered in 2015 to all mothers (n=320) who gave birth to a live-born during a 1-year period in 31 villages which had EMM in two provinces, Dien Bien and Kon Tum. A multivariate logistic regression model was used to examine the association between all potential factors and the use of services provided by EMMs. Results: We found that EMMs provided more antenatal care and postnatal care as compared with delivery services, which corresponded to their job descriptions. The results also showed that utilization of antenatal care provided by EMMs was lower than that of postnatal care. The proportion of those who never heard about EMM was high (24%). Among the mothers who knew about EMM services, 33.4% had antenatal checkups, 20.1% were attended during home deliveries, and 57.3% had postnatal visits by an EMM. Key factors that determined the use of EMM services included knowledge of the location of EMM’s house, being aware about EMMs by health workers, trust in services provided by EMMs, and perception that many others mothers in a village also knew about EMM services. Conclusion: EMM seems to be an important mechanism to ensure assistance during home births and postnatal care for ethnic minority groups, who are often resistant to attend health facilities. Building trust and engaging with communities are the key facilitators to increase the utilization of services provided by EMMs. Communication campaigns to raise awareness about EMMs and to promote their services in the village, particularly by other health workers, represent an important strategy to further improve effectiveness of EMM scheme

Decline in mortality, AIDS, and hospital admissions in perinatally HIV-1 infected children in the United Kingdom and Ireland.

OBJECTIVE: To describe changes in demographic factors, disease progression, hospital admissions, and use of antiretroviral therapy in children with HIV. DESIGN: Active surveillance through the national study of HIV in pregnancy and childhood (NSHPC) and additional data from a subset of children in the collaborative HIV paediatric study (CHIPS). SETTING: United Kingdom and Ireland. PARTICIPANTS: 944 children with perinatally acquired HIV-1 under clinical care. MAIN OUTCOME MEASURES: Changes over time in progression to AIDS and death, hospital admission rates, and use of antiretroviral therapy. RESULTS: 944 children with perinatally acquired HIV were reported in the United Kingdom and Ireland by October 2002; 628 (67%) were black African, 205 (22%) were aged > or = 10 years at last follow up, 193 (20%) are known to have died. The proportion of children presenting who were born abroad increased from 20% in 1994-5 to 60% during 2000-2. Mortality was stable before 1997 at 9.3 per 100 child years at risk but fell to 2.0 in 2001-2 (trend P < 0.001). Progression to AIDS also declined (P < 0.001). From 1997 onwards the proportion of children on three or four drug antiretroviral therapy increased. Hospital admission rates declined by 80%, but with more children in follow up the absolute number of admissions fell by only 26%. CONCLUSION: In children with HIV infection, mortality, AIDS, and hospital admission rates have declined substantially since the introduction of three or four drug antiretroviral therapy in 1997. As infected children in the United Kingdom and Ireland are living longer, there is an increasing need to address their medical, social, and psychological needs as they enter adolescence and adult life

Outcomes after viral load rebound on fi rst-line antiretroviraltreatment in children with HIV in the UK and Ireland:an observational cohort study.

BACKGROUND: About a third of children with HIV have virological failure within 2 years of beginning antiretroviral treatment (ART). We assessed the probability of switch to second-line ART or virological re-suppression without switch in children who had virological rebound on first-line ART in the UK and Ireland. METHODS: In this study, we used data reported to the Collaborative HIV Paediatric Study (CHIPS), a national multicentre observational cohort. We included children with virological rebound (confirmed viral load>400 copies per mL after suppression<400 copies per mL) on first-line ART. We did a competing-risk analysis to estimate the probability of switch to second-line treatment, confirmed resuppression (two consecutive viral load measurments<400 copies per mL) without switch, and continued viral load above 400 copies per mL without switch. We also assessed factors that predicted a faster time to switch. FINDINGS: Of the 900 children starting first-line ART who had a viral load below 400 copies per mL within a year of starting treatment, 170 (19%) had virological rebound by a median of 20·6 months (IQR 9·7–40·5). At rebound, median age was 10·6 years (5·6–13·4), median viral load was 3·6 log10 copies per mL (3·1–4·2), and median CD4% was 24% (17–32). 89 patients (52%) switched to second-line ART at a median of 4·9 months (1·7–13·4) after virological rebound, 53 (31%) resuppressed without switch (19 [61%] of 31 patients on a first-line regimen that included a protease inhibitor and 31 [24%] of 127 patients on a first-line regimen that included a non-nucleoside reverse transcriptase inhibitor; NNRTI), and 28 (16%) neither resuppressed nor switched. At 12 months after rebound, the estimated probability of switch was 38% (95% CI 30–45) and of resuppression was 27% (21–34). Faster time to switch was associated with a higher viral load (p<0·0001), later calendar year at virological rebound (p=0·02), and being on an NNRTI-based or triple nucleoside reverse transcriptase inhibitor-based versus protease-inhibitor-based first-line regimen (p=0·001). INTERPRETATION: A third of children with virological rebound resuppressed without switch. Clinicians should consider the possibility of resuppression with adherence support before switching treatment in children with HIV. FUNDING: NHS England (London Specialised Commissioning Group)

Finding needles in haystacks: linking scientific names, reference specimens and molecular data for Fungi

DNA phylogenetic comparisons have shown that morphology-based species recognition often underestimates fungal diversity. Therefore, the need for accurate DNA sequence data, tied to both correct taxonomic names and clearly annotated specimen data, has never been greater. Furthermore, the growing number of molecular ecology and microbiome projects using high-throughput sequencing require fast and effective methods for en masse species assignments. In this article, we focus on selecting and re-annotating a set of marker reference sequences that represent each currently accepted order of Fungi. The particular focus is on sequences from the internal transcribed spacer region in the nuclear ribosomal cistron, derived from type specimens and/or ex-type cultures. Re-annotated and verified sequences were deposited in a curated public database at the National Center for Biotechnology Information (NCBI), namely the RefSeq Targeted Loci (RTL) database, and will be visible during routine sequence similarity searches with NR_prefixed accession numbers. A set of standards and protocols is proposed to improve the data quality of new sequences, and we suggest how type and other reference sequences can be used to improve identification of Fungi

Underutilization of Social Insurance among the Poor: Evidence from the Philippines

Many developing countries promote social health insurance as a means to eliminate unmet health needs. However, this strategy may be ineffective if there are barriers to fully utilizing insurance.We analyzed the utilization of social health insurance in 30 hospital districts in the central regions of the Philippines between 2003 and 2007. Data for the study came from the Quality Improvement Demonstration Study (QIDS) and included detailed patient information from exit interviews of children under 5 years of age conducted in seven waves among public hospital districts located in the four central regions of the Philippines. These data were used to estimate and identify predictors of underutilization of insurance benefits--defined as the likelihood of not filing claims despite having legitimate insurance coverage--using logistic regression.Multivariate analyses using QIDS data from 2004 to 2007 reveal that underutilization averaged about 15% throughout the study period. Underutilization, however, declined over time. Among insured hospitalized children, increasing length of stay in the hospital and mother's education, were associated with less underutilization. Being in a QIDS intervention site was also associated with less underutilization and partially accounts for the downward trend in underutilization over time.The surprisingly high level of insurance underutilization by insured patients in the QIDS sites undermines the potentially positive impact of social health insurance on the health of the marginalized. In the Philippines, where the largest burden of health care spending falls on households, underutilization suggests ineffective distribution of public funds, failing to reach a significant proportion of households which are by and large poor. Interventions that improve benefit awareness may combat the problem of underutilization and should be the focus of further research in this area

Risk estimates of recurrent congenital anomalies in the UK: a population-based register study

BACKGROUND: Recurrence risks for familial congenital anomalies in successive pregnancies are known, but this information for major structural anomalies is lacking. We estimated the absolute and relative risks of recurrent congenital anomaly in the second pregnancy for women with a history of a congenital anomaly in the first pregnancy; for all major anomaly groups and subtypes. METHODS: Population-based register data on 18,605 singleton pregnancies affected by major congenital anomaly occurring in 872,493 singleton stillbirths, live births and terminations of pregnancy for fetal anomaly were obtained from the Northern Congenital Abnormality Survey, North of England, UK, for 1985-2010. Absolute risks (ARs) and relative risks (RRs) for recurrent congenital anomaly (overall, from a similar group, from a dissimilar group) in the second pregnancy were estimated by history of congenital anomaly (overall, by group, by subtype) in the first pregnancy. RESULTS: The estimated prevalences of congenital anomaly in first and second pregnancies were 276 (95% CI 270-281) and 163 (95% CI 159-168) per 10,000 respectively. For women whose first pregnancy was affected by congenital anomaly, the AR of recurrent congenital anomaly in the second pregnancy was 408 (95% CI 365-456) per 10,000; 2.5 (95% CI 2.3-2.8, p<0.0001) times higher than for those with unaffected first pregnancies. For similar anomalies, the recurrence risk was considerably elevated (RR=23.8, 95% CI 19.6-27.9, P<0.0001) while for dissimilar anomalies the increase was more modest (RR=1.4, 95% CI 1.2-1.6, P=0.001), although the ARs for both were 2%. CONCLUSIONS: Absolute recurrence risks varied between 1 in 20 and 1 in 30 for most major anomaly groups. At pre-conception and antenatal counselling, women whose first pregnancy was affected by a congenital anomaly and who are planning a further pregnancy may find it reassuring that despite high relative risks, the absolute recurrence risk is relatively low