Prevalence of metabolic syndrome among adolescents in India: a population-based study.

BACKGROUND: In India, the prevalence of overweight among adolescents is on the rise, setting the stage for an increase in metabolic syndrome (MS). This paper presents the national prevalence of MS in adolescents in India. METHODS: A nationally representative data of adolescents (10-19 years) from the Comprehensive National Nutrition Survey was used. MS was defined based on the NCEP-ATP III criteria for adolescents. Bivariate analysis was used to report socio-demographic differentials in prevalence and to assess interstate variability. Multivariate logistic regression model was constructed to measure the association between socio-demographic characteristics and prevalence of MS. Census data from 2011 was projected to 2017 to calculate burden. RESULTS: The prevalence of MS was 5.2% among adolescents. 11.9%, 15.4%, 26.0%, 31.9% and 3.7% had central obesity, high blood pressure, hypertriglyceridemia, low HDL-cholesterol and high fasting glucose, respectively. The prevalence was higher among males (5.7% vs. 4.7%, adjusted odds ratio (AOR): 1.3, 95% confidence interval [CI]: 1.0, 1.6), those residing in urban areas (7.9% vs 4.2%, AOR: 1.4, 95% CI: 1.1, 1.8), and from wealthier households as compared to their counterparts (8.3% vs. 2.4%, AOR: 3.4, 95% CI: 2.1, 5.5). There was wide interstate variability in the prevalence of MS (0.5% - 16.5%). In 2017, 14.2 million adolescents had MS in India. CONCLUSIONS: The prevalence of MS among adolescents in India is low and clustered in urban areas and richer households. Early prevention interventions promoting a healthy lifestyle, especially in high prevalence areas, are needed to keep MS from becoming a public health issue.

National guidelines for data quality in surveys: An overview.

Good quality health, nutrition and demographic survey data are vital for evidence-based decision-making. Existing literature indicates system specific, data collection and reporting gaps that affect quality of health, nutrition and demographic survey data, thereby affecting its usability and relevance. To mitigate these, the National Data Quality Forum (NDQF), under the Indian Council of Medical Research (ICMR) - National Institute of Medical Statistics (NIMS) developed the National Guidelines for Data Quality in Surveys delineating assurance mechanisms to generate standard quality data in surveys. The present article highlights the principles from the guidelines for informing survey researchers/organizations in generating good quality survey data. It describes the process of development of the national guidelines, principles for each of the survey phases listed in the document and applicability of them to data user for ensuring data quality. The guidelines may be useful to a broad-spectrum of audience such as data producers from government and non-government organizations, policy makers, research institutions, as well as individual researchers, thereby playing a vital role in improving quality of health, nutrition and demographic data ecosystem.

Osteogenesis imperfecta: Novel genetic variants and clinical observations from a clinical exome study of 54 Indian patients.

Osteogenesis imperfecta (OI) is a group of inherited disorders with increased bone fragility and wide genetic heterogeneity. We report the outcome of clinical exome sequencing validated by Sanger sequencing in clinically diagnosed 54 OI patients in Indian population. In 52 patients, we report 20 new variants involving both dominant and recessive OI-specific genes and correlate these with phenotypes. COL1A1 and COL1A2 gene variants were identified in 44.23%, of which 28.84% were glycine substitution abnormalities. Two novel compound heterozygous variants in the FKBP10 gene were seen in two unrelated probands. A novel heterogeneous duplication of chromosomal region chr17: 48268168-48278884 from exons 1-33 of the COL1A1 gene was found in one proband. In five probands, there were additional variants in association with OI. These were ANO5 in association with CRTAP in two probands of the same family causing gnathodiaphyseal dysplasia, COL5A2 with LEPRE1 causing Ehlers Danlos syndrome, COL11A1 in addition to COL1A1 causing Stickler syndrome, and a previously unreported combination of SLC34A1 gene variant with FKBP10 leading to Fanconi renal tubular syndrome type II. Our findings demonstrate the efficacy of clinical exome sequencing in screening OI patients, classifying its subtypes, and identifying associated disorders in consanguineous populations.

Socio-economic inequality in anthropometric failure among children aged under 5 years in India: evidence from the Comprehensive National Nutrition Survey 2016-18.

BACKGROUND: Conventional indicators used to access the nutritional status of children tend to underestimate the overall undernutrition in the presence of multiple anthropometric failures. Further, factors contributing to the rich-poor gap in the composite index of anthropometric failure (CIAF) have not been explored. This study aims to estimate the prevalence of CIAF and quantify the contribution of factors that explain the rich-poor gap in CIAF. METHODS: The present study used data of 38,060 children under the age of five years and their biological mothers, drawn from the nationally representative Comprehensive National Nutrition Survey of children and adolescents aged 0-19 years in India. The CIAF outcome variable in this study provide an overall prevalence of undernutrition, with six mutually exclusive anthropometric measurements of height-for-age, height-for-weight, and weight-for-age, calculated using the World Health Organization (WHO) Multicenter Growth Reference Study. Multivariate regression and decomposition analysis were used to examine the association between covariates with CIAF and to estimate the contribution of different covariates in the existing rich-poor gap. RESULTS: An overall CIAF prevalence of 48.2% among children aged aged under 5 years of age was found in this study. 6.0% children had all three forms of anthropometric failures. The odds of CIAF were more likely among children belonging to poorest households (AOR: 2.41, 95% CI: 2.12-2.75) and those residing in urban area (AOR: 1.06, 95% CI 1.00-1.11). Children of underweight mothers and those with high parity were at higher risk of CIAF (AOR: 1.51, 95% CI: 1.42-1.61) and (AOR: 1.15, 95% CI: 1.08-1.22), respectively. Children of mother exposed to mass media were at lower risk of CIAF (AOR: 0.87, 95% CI: 0.81-0.93). CONCLUSION: This study estimated a composite index to assess the overall anthropometric failure, which also provides a broader understanding of the extent and pattern of undernutrition among children. Findings show that maternal covariates contribute the most to the rich-poor gap. As well, the findings suggest that intervention programs with a targeted approach are crucial to reach the most vulnerable groups and to reduce the overall burden of undernutrition.

Association of maternal height and body mass index with nutrition of children under 5 years of age in India: Evidence from Comprehensive National Nutrition Survey 2016-18.

BACKGROUND AND OBJECTIVES: Child undernutrition remains an area of public health concern across the globe, particularly in developing countries like India. Previous studies have focused on the association of maternal nutrition with premature pregnancy and birthweight of child, with few establishing the intergenerational effect but limited to select populations and geography. METHODS AND STUDY DESIGN: This study used data from 35,452 children aged under 5 years and their biological mother from nationally representative Comprehensive National Nutrition Survey (CNNS) in India. The outcome variables were anthropometric indices: height-for-age, weightfor- height, and weight-for-age. The exposure variables were maternal height and body mass index (BMI). Multivariate regression analysis was used to examine the association between maternal height and BMI with child undernutrition. RESULTS: Out of total number of mothers, 11.1% were short in stature and 28% were underweight. Of total number of children, 33.9%, 17.3% and 32.7% were stunted, wasted, and underweight respectively. Children born to mother with short stature were more likely to be stunted (OR=1.73, 95% CI 1.59-1.89), wasted (OR=1.26, 95% CI 1.12-1.41) and underweight (OR=1.64, 95% CI 1.50-1.79). Similarly, children with underweight mother were more likely to be stunted (OR=1.63, 95% CI 1.53-1.73), wasted (OR=1.64, 95% CI 1.52-1.77) and underweight (OR=2.14, 95% CI 2.01-2.27). CONCLUSIONS: The study shows a strong association between maternal and child undernutrition demonstrating intergenerational linkage between the two. The national programme needs to focus on holistic and comprehensive nutrition strategy with targeted interventions to improve both maternal and child health.

Radial Extracorporeal Shock Wave Treatment Promotes Bone Growth and Chondrogenesis in Cultured Fetal Rat Metatarsal Bones.

BACKGROUND: Substantial evidence exists to show the positive effects of radialextracorporeal shock wave therapy (ESWT) on bone formation. However, it is unknown whether rESWT can act locally at the growth plate level to stimulate linear bone growth. One way to achieve this is to stimulate chondrogenesis in the growth plate without depending on circulating systemic growth factors. We wished to see whether rESWT would stimulate metatarsal rat growth plates in the absence of vascularity and associated systemic growth factors. QUESTIONS/PURPOSES: To study the direct effects of rESWT on growth plate chondrogenesis, we asked: (1) Does rESWT stimulate longitudinal bone growth of ex vivo cultured bones? (2) Does rESWT cause any morphological changes in the growth plate? (3) Does rESWT locally activate proteins specific to growth plate chondrogenesis? METHODS: Metatarsal bones from rat fetuses were untreated (controls: n = 15) or exposed to a single application of rESWT at a low dose (500 impulses, 5 Hz, 90 mJ; n = 15), mid-dose (500 impulses, 5 Hz, 120 mJ; n = 14) or high dose (500 impulses, 10 Hz, 180 mJ; n = 34) and cultured for 14 days. Bone lengths were measured on Days 0, 4, 7, and 14. After 14 days of culturing, growth plate morphology was assessed with a histomorphometric analysis in which hypertrophic cell size (> 7 µm) and hypertrophic zone height were measured (n = 6 bones each). Immunostaining for specific regulatory proteins involved in chondrogenesis and corresponding staining were quantitated digitally by a single observer using the automated threshold method in ImageJ software (n = 6 bones per group). A p value < 0.05 indicated a significant difference. RESULTS: The bone length in the high-dose rESWT group was increased compared with that in untreated controls (4.46 mm ± 0.75 mm; 95% confidence interval, 3.28-3.71 and control: 3.50 mm ± 0.38 mm; 95% CI, 4.19-4.72; p = 0.01). Mechanistic studies of the growth plate's cartilage revealed that high-dose rESWT increased the number of proliferative chondrocytes compared with untreated control bones (1363 ± 393 immunopositive cells per bone and 500 ± 413 immunopositive cells per bone, respectively; p = 0.04) and increased the diameter of hypertrophic chondrocytes (18 ± 3 µm and 13 ± 3 µm, respectively; p < 0.001). This was accompanied by activation of insulin-like growth factor-1 (1015 ± 322 immunopositive cells per bone and 270 ± 121 immunopositive cells per bone, respectively; p = 0.043) and nuclear factor-kappa beta signaling (1029 ± 262 immunopositive cells per bone and 350 ± 60 immunopositive cells per bone, respectively; p = 0.01) and increased levels of the anti-apoptotic proteins B-cell lymphoma 2 (718 ± 86 immunopositive cells per bone and 35 ± 11 immunopositive cells per bone, respectively; p < 0.001) and B-cell lymphoma-extra-large (107 ± 7 immunopositive cells per bone and 34 ± 6 immunopositive cells per bone, respectively; p < 0.001). CONCLUSION: In a model of cultured fetal rat metatarsals, rESWT increased longitudinal bone growth by locally inducing chondrogenesis. To verify whether rESWT can also stimulate bone growth in the presence of systemic circulatory factors, further studies are needed. CLINICAL RELEVANCE: This preclinical proof-of-concept study shows that high-dose rESWT can stimulate longitudinal bone growth and growth plate chondrogenesis in cultured fetal rat metatarsal bones. A confirmatory in vivo study in skeletally immature animals must be performed before any clinical studies.

Factors associated with HIV testing among male injecting drug users: findings from a cross-sectional behavioural and biological survey in Manipur and Nagaland, India.

BACKGROUND: Although targeted interventions in India require all high-risk groups, including injecting drug users (IDUs), to test for HIV every 6 months, testing uptake among IDUs remains far from universal. Our study estimates the proportion of IDUs who have taken an HIV test and identifies the factors associated with HIV testing uptake in Nagaland and Manipur, two high HIV prevalence states in India where the epidemic is driven by injecting drug use. METHODS: Data are drawn from the cross-sectional Integrated Behavioural and Biological Assessment (2009) of 1650 male IDUs from two districts each of Manipur and Nagaland. Participants were recruited using respondent-driven sampling (RDS). Descriptive data were analysed using RDSAT 7.1. Multivariate logistic regression analysis was undertaken using STATA 11 to examine the association between HIV testing and socio-demographic, behavioural and programme exposure variables. RESULTS: One third of IDUs reported prior HIV testing, of whom 8 % had tested HIV-positive. Among those without prior testing, 6.2 % tested HIV-positive in the current survey. IDUs aged 25-34 years (adjusted odds ratio (OR) = 1.41; 95 % confidence interval (CI) = 1.03-1.93), married (Adjusted OR = 1.56; 95 % CI = 1.15-2.12), had a paid sexual partner (Adjusted OR = 1.64; 95 % CI = 1.24-2.18), injected drugs for more than 36 months (Adjusted OR = 1.38; 95 % CI = 1.06-1.81), injected frequently (Adjusted OR = 1.49; 95 % CI = 1.12-1.98) and had high-risk perception (Adjusted OR = 1.68; 95 % CI = 1.32-2.14) were more likely than others to test for HIV. Compared to those with no programme exposure, IDUs who received counselling, or counselling and needle/syringe services, were more likely to test for HIV. CONCLUSIONS: HIV testing uptake among IDUs is low in Manipur and Nagaland, and a critical group of HIV-positive IDUs who have never tested for HIV are being missed by current programmes. This study identifies key sub-groups-including early initiators, short duration and less frequent injectors, perceived to be at low risk-for promoting HIV testing. Providing needles/syringes alone is not adequate to increase HIV testing; additionally, interventions must provide counselling services to inform all IDUs about HIV testing benefits, facilitate visits to testing centres and link those testing positive to timely treatment and care.

The effect of mobility on sexual risk behaviour and HIV infection: a cross-sectional study of men who have sex with men in southern India.

OBJECTIVES: Mobility is an important factor contributing to the spread of HIV among key population at risk for HIV; however, research linking this relationship among men who have sex men (MSM) is scarce in India. This study examines the association between mobility and sexual risk behaviour and HIV infection among MSM in southern India. METHODS: Data are drawn from a cross-sectional biobehavioural survey of 1608 self-identified MSM from four districts of Andhra Pradesh in India, recruited through a probability-based sampling in 2009-2010. Logistic regression models were used to estimate odds ratios and 95% CIs for sexual risk behaviours (unprotected sex with any male partner) and HIV infection based on the mobility status (travelled and had sex in the past year) after adjusting for sociodemographics and risk behaviours. RESULTS: Of the 1608 MSM, one-fourth (26%) were mobile. Of these, three-fourths had travelled across districts but within the state (56%), and one-fifth (20%) across states. As compared to non-mobile MSM, a higher proportion of MSM who were mobile across districts (adjusted (OR=1.42, 95% CI 1.04 to 1.95) or states (adjusted OR=3.20, 95% CI 1.65 to 6.17) reported having unprotected sex with any male sexual partner. Further, mobility across districts (adjusted OR=1.43, 95% CI 1.01 to 2.03) or states (adjusted OR=2.45, 95% CI 1.46 to 4.10) was significantly associated with HIV infection. CONCLUSIONS: Mobile MSM have a higher likelihood of contracting HIV. Interventions extending the ways to reach out to MSM with greater mobility may augment ongoing efforts to reduce the spread of HIV/AIDS in India.

Female sex worker's participation in the community mobilization process: two distinct forms of participations and associated contextual factors.

BACKGROUND: Community mobilization is a participatory intervention strategy used among Female Sex Workers (FSW's) to address HIV risks through behavior change and self empowerment. This study quantitatively measure and differentiate theoretically defined forms of FSW participation's and identify their contextual associated factors. METHOD: Data was derived from cross-sectional Integrated Bio Behavioral Assessment conducted among FSW's in Andhra Pradesh (AP) (n = 3370), Maharashtra (MH) (n = 3133) and Tamil Nadu (TN) (n = 2140) of India during 2009-2010. Information's about socio-demography, community mobilization and participation experiences were collected. Conceptual model for two contexts of mobilization entailing distinct FSW participations were defined as participation in "collective" and "public" spaces respectively. Bivariate and multiple regression analysis were used. RESULT: The level of participation in "collective" and "public" spaces was lowest in MH (43.9% & 11.7% respectively), higher in TN (82.2% & 22.5% respectively) and AP (64.7% & 33.1%). Bivariate and multivariate regression analysis highlighted the distinct nature of "participations" through their varied associations with FSW mobilization and background status.In MH, street FSWs showed significantly lower collective participation (36.5%) than brothel FSWs (46.8%) and street FSWs showed higher public participation (16.2%) than brothel FSWs (9.7%). In AP both collective and public participation were significantly high among street FSWs (62.7% and 34.7% respectively) than brothel FSW's (55.2% and 25.4% respectively).Regression analysis showed FSWs with "community identity", were more likely to participate in public spaces in TN and AP (AOR 2.4, 1.5-3.8 & AOR 4.9, CI 2.3-10.7) respectively. FSWs with "collective identity" were more likely to participate in collective spaces in TN, MH and AP (AOR 27.2 CI 13.7-53.9; AOR 7.3, CI 3.8-14.3; AOR 5.7 CI 3-10.9 respectively). FSWs exhibiting "collective agency" were more likely to participate in public spaces in TN, MH and AP (AOR 2.3 CI 1-3.4; AOR 4.5- CI 2.6-7.8; AOR 2.2 CI 1.5-3.1) respectively. CONCLUSION: Findings reveal FSWs participation as a dynamic process inherently evolving along with the community mobilization process in match with its contexts. Participation in "Collective" and Public spaces" is indicators, symbolizing FSWs passage from the disease prevention objectives towards empowerment, which would help better understand and evaluate community mobilization interventions.

Enhanced encapsulation of chondrocytes within a chitosan/hyaluronic acid hydrogel: a new technique.

Two encapsulation techniques for rabbit chondrocytes in chitosan/hyaluronic acid gel have been compared. The standard technique involves the cross-linking of chitosan and hyaluronic acid at 2:1 (w/w). In the modified technique, cells were initially added to 33% of hyaluronic acid dialdehyde and the gelation process was completed with the remaining 67%. This minimised the cell loss and improved the encapsulation of the cells. By the third week, the modified technique showed better seeding density, with matrix synthesis (per scaffold) of 11 µg as compared to 1.1 µg in the current technique. Relative expression of collagen II with the current technique and the modified technique were 6.4% and ~1,600% respectively. The modified technique was superior for matrix synthesis and maintenance of phenotype.

Olive oil based novel thermo-reversible emulsion hydrogels for controlled delivery applications.

Gels have been considered as a popular mode of delivering medicament for the treatment of sexually transmitted diseases (STDs) (e.g. human immunodeficiency virus, bacterial vaginosis, epididymitis, human papillomavirus infection and condylomata acuminata etc.). The present study discusses the development of novel olive oil based emulsion hydrogels (EHs) using sorbitan monopalmitate as the structuring agent. The developed EHs may be tried as drug delivery vehicle for the treatment of STDs. The formation of EHs was confirmed by fluorescence and confocal microscopy. FTIR studies suggested intermolecular hydrogen bonding amongst the components of the EHs. X-ray diffraction study suggested the amorphous nature of the EHs. The developed EHs have shown non-Newtonian flow behavior. The EHs were found to be biocompatible. The formulations were able to effectively deliver two model antimicrobial drugs (e.g. ciprofloxacin and metronidazole), commonly used in the treatment of the STDs.

Effect of peer-led outreach activities on injecting risk behavior among male drug users in Haryana, India.

BACKGROUND: For the past two decades, there has been an enduring HIV epidemic among injecting drug users (IDUs) in India, and the Indian national AIDS control program (NACP) led by the National AIDS Control Organization (NACO) has kept IDUs at the forefront along with other key populations, in its efforts to prevent HIV. Given this, the objective of this study is to examine the association between IDUs' degree of exposure to peer-led education sessions (under NACP) and their needle sharing practices in Haryana, India. METHODS: The data for this study were drawn from a program monitoring system for the years 2009-2010 and 2010-2011. The relationship between IDUs' background characteristics/injecting practices and degree of exposure to the program was assessed using chi-square and Student's t tests. Generalized estimating equations (GEE) were used to examine changes in needle sharing practices over time by degree of exposure to peer-led education sessions. Further, the analysis was stratified by frequency of injecting drug use. All statistical analyses were conducted using STATA version 11. RESULTS: The proportion of IDUs who shared needles substantially decreased from 2009 to 2011, particularly among those who attended three or more peer-led education sessions (49% vs 11%, p < 0.001) in a month. Further, subgroup analysis by frequency of injecting drugs demonstrates that this decline was significant among IDUs who injected frequently (adjusted odds ratio = 0.6, 95% confidence interval = 0.3-0.9, p = 0.043). CONCLUSION: The study results indicate that repeated peer-led outreach sessions are more effective than exposure to a single education session. Hence, HIV prevention programs must promote repeated peer contacts with IDUs every month (at least two meetings) in order to promote safe injecting practices and behavior change.

HIV risk behaviors of male injecting drug users and associated non-condom use with regular female sexual partners in north-east India.

BACKGROUND: In the context of increasing HIV prevalence among women in regular sexual partnerships, this paper examines the relationship between male injecting drug users' (IDUs) risky injecting practices and sexual risk behaviors with casual partners and inconsistent condom use with regular partners. METHODS: Data were drawn from the behavioral tracking survey, conducted in 2009 with 1,712 male IDUs in two districts each of Manipur and Nagaland states, in north-east India. IDUs' risky behaviors were determined using two measures: ever shared needles/syringes and engaged in unprotected sex with casual paid/unpaid female partners in the past 12 months. Inconsistent condom use with regular sexual partners (wife/girlfriend) in the past 12 months was assessed in terms of non-condom use in any sexual encounter. RESULTS: More than one-quarter of IDUs had shared needles/syringes, and 40% had a casual sexual partner. Among those who had casual sexual partners, 65% reported inconsistent condom use with such partners. IDUs who shared needles/syringes were more likely to engage in unprotected sex with their regular partners (95% vs 87%; adjusted OR = 2.31, 95% CI = 1.30-4.09). Similarly, IDUs who reported inconsistent condom use with casual partners were more likely to report unprotected sex with their regular partners (97% vs 66%; adjusted OR = 18.14, 95% CI = 6.82-48.21). CONCLUSION: IDUs who engage in risky injecting and/or sexual behaviors with casual partners also report non-condom use with their regular sex partners, suggesting the high likelihood of HIV transmission from IDUs to their regular sexual partners. Risk reduction programs for IDUs need to include communication about condom use in all relationships in an effort to achieve the goal of zero new infections.

Neuronal regulation of bone and tendon injury repair: a focused review.

Beyond the sensation of pain, peripheral nerves have been shown to play crucial roles in tissue regeneration and repair. As a highly innervated organ, bone can recover from injury without scar formation, making it an interesting model in which to study the role of nerves in tissue regeneration. As a comparison, tendon is a musculoskeletal tissue that is hypo-innervated, with repair often resulting in scar formation. Here, we reviewed the significance of innervation in three stages of injury repair (inflammatory, reparative, and remodeling) in two commonly injured musculoskeletal tissues: bone and tendon. Based on this focused review, we conclude that peripheral innervation is essential for phases of proper bone and tendon repair, and that nerves may dynamically regulate the repair process through interactions with the injury microenvironment via a variety of neuropeptides or neurotransmitters. A deeper understanding of neuronal regulation of musculoskeletal repair, and the crosstalk between nerves and the musculoskeletal system, will enable the development of future therapies for tissue healing.

Accumulating evidence has shown that, across organs systems, peripheral nerves regulate the process of tissue repair and regeneration. This is particularly relevant in the context of musculoskeletal injuries such as those affecting the bone and tendon. The question then arises: what is the function of peripheral innervation in the repair of bone and tendon injuries? This review offers an in-depth look at the ways in which nerves regulate the healing of bone and tendon injuries at various stages of recovery. A deeper comprehension of the influence of nerves on the repair of these tissues could pave the way for the development of future therapeutic strategies for tissue healing.

Vulnerability to Sexually Transmitted Infections (STI) / Human Immunodeficiency Virus (HIV) among adolescent girls and young women in India: A rapid review.

Limited evidence is available on the vulnerability of Adolescent Girls and Young Women (AGYW) to sexual risk behaviour and STI/HIV. Though there are almost no statistics available on vulnerability, related literature suggests that AGYW have low awareness about sexual risk behaviour/ transmission and the prevalence of STI/HIV, making them vulnerable. We conducted a rapid review of peer-reviewed studies addressing transmission network, prevalence, incidence awareness, common determinants of sexual risk behaviour/STI/HIV, health-seeking behaviour and existing interventions addressing the situation among AGYW (age 15-24) to inform the evidence gap in this crucial area of research. We registered the study in PROSPERO (CRD42023403713). We developed detailed inclusion/exclusion criteria, searched JSTOR, PubMed, Google Scholar, Science Direct and Population Council Knowledge Commons databases and followed the guidance from Cochrane Rapid Review to develop the rapid review. We also searched the bibliography of the included studies. We included the English language peer-reviewed quantitative, qualitative, mixed method studies published from Jan 1 2000 to Mar 31 2023. Six reviewers extracted data, and the seventh reviewer independently assessed the quality. Ninety-six studies met the inclusion criteria. We used descriptive statistics and narrative synthesis methods for data analysis. We also conducted a Risk of Bias Assessment (RoB) to check the quality of the included studies. Inadequate literature was found on the transmission network. Prevalence and awareness of STI/HIV are low among AGYW. However, Female Sex Workers, sex-trafficked women or drug users in this age group suffer more. Age, education, income, relationship dynamics with spouses/partners, multiple partners, and substance use are crucial in determining STI/HIV. Traditional sources of health seeking are more popular than formal sources because of social stigma. Mass media campaigns, community mobilization programs, and life skills training programs increase awareness about HIV, condom use and self-efficacy. The inclusion of only English language studies and not conducting meta-analysis because of high heterogeneity are some of the limitations of the study.

Vegfc-expressing cells form heterotopic bone after musculoskeletal injury.

Heterotopic ossification (HO) is a challenging condition that occurs after musculoskeletal injury and is characterized by the formation of bone in non-skeletal tissues. While the effect of HO on blood vessels is well established, little is known about its impact on lymphatic vessels. Here, we use a mouse model of traumatic HO to investigate the relationship between HO and lymphatic vessels. We show that injury triggers lymphangiogenesis at the injury site, which is associated with elevated vascular endothelial growth factor C (VEGF-C) levels. Through single-cell transcriptomic analyses, we identify mesenchymal progenitor cells and tenocytes as sources of Vegfc. We demonstrate by lineage tracing that Vegfc-expressing cells undergo osteochondral differentiation and contribute to the formation of HO. Last, we show that Vegfc haploinsufficiency results in a nearly 50% reduction in lymphangiogenesis and HO formation. These findings shed light on the complex mechanisms underlying HO formation and its impact on lymphatic vessels.

Validating the indicator "maternal death review coverage" to improve maternal mortality data: A retrospective analysis of district, facility, and individual medical record data.

BACKGROUND: Understanding causes and contributors to maternal mortality is critical from a quality improvement perspective to inform decision making and monitor progress toward ending preventable maternal mortality. The indicator "maternal death review coverage" is defined as the percentage of maternal deaths occurring in a facility that are audited. Both the numerator and denominator of this indicator are subject to misclassification errors, underreporting, and bias. This study assessed the validity of the indicator by examining both its numerator-the number and quality of death reviews-and denominator-the number of facility-based maternal deaths and comparing estimates of the indicator obtained from facility- versus district-level data. METHODS AND FINDINGS: We collected data on the number of maternal deaths and content of death reviews from all health facilities serving as birthing sites in 12 districts in three countries: Argentina, Ghana, and India. Additional data were extracted from health management information systems on the number and dates of maternal deaths and maternal death reviews reported from health facilities to the district-level. We tabulated the percentage of facility deaths with evidence of a review, the percentage of reviews that met the World Health Organization defined standard for maternal and perinatal death surveillance and response. Results were stratified by sociodemographic characteristics of women and facility location and type. We compared these estimates to that obtained using district-level data. and looked at evidence of the review at the district/provincial level. Study teams reviewed facility records at 34 facilities in Argentina, 51 facilities in Ghana, and 282 facilities in India. In total, we found 17 deaths in Argentina, 14 deaths in Ghana, and 58 deaths in India evidenced at facilities. Overall, >80% of deaths had evidence of a review at facilities. In India, a much lower percentage of deaths occurring at secondary-level facilities (61.1%) had evidence of a review compared to deaths in tertiary-level facilities (92.1%). In all three countries, only about half of deaths in each country had complete reviews: 58.8% (n = 10) in Argentina, 57.2% (n = 8) in Ghana, and 41.1% (n = 24) in India. Dramatic reductions in indicator value were seen in several subnational geographic areas, including Gonda and Meerut in India and Sunyani in Ghana. For example, in Gonda only three of the 18 reviews conducted at facilities met the definitional standard (16.7%), which caused the value of the indicator to decrease from 81.8% to 13.6%. Stratification by women's sociodemographic factors suggested systematic differences in completeness of reviews by women's age, place of residence, and timing of death. CONCLUSIONS: Our study assessed the validity of an important indicator for ending preventable deaths: the coverage of reviews of maternal deaths occurring in facilities in three study settings. We found discrepancies in deaths recorded at facilities and those reported to districts from facilities. Further, few maternal death reviews met global quality standards for completeness. The value of the calculated indicator masked inaccuracies in counts of both deaths and reviews and gave no indication of completeness, thus undermining the ultimate utility of the measure in achieving an accurate measure of coverage.

Validating the implementation of an indicator reporting policies and laws on free public maternal health-related services in the era of universal health coverage: A multi-country cross-sectional study.

BACKGROUND: The concept of universal health coverage (UHC) encompasses both access to essential health services and freedom from financial harm. The World Health Organization's Maternal Newborn Child and Adolescent Health (MNCAH) Policy Survey collects data on policies that have the potential to reduce maternal morbidity and mortality. The indicator, "Are the following health services provided free of charge at point-of-use in the public sector for women of reproductive age?", captures the free provision of 13 key categories of maternal health-related services, to measure the success of UHC implementation with respect to maternal health. However, it is unknown whether it provides a valid measure of the provision of free care. Therefore, this study compared free maternal healthcare laws and policies against actual practice in three countries. METHODS AND FINDINGS: We conducted a cross-sectional study in four districts/provinces in Argentina, Ghana, and India. We performed desk reviews to identify free care laws and policies at the country level and compared those with reports at the global level. We conducted exit interviews with women aged 15-49 years who used a component service or their accompanying persons, as well as with facility chief financial officers or billing administrators, to determine if women had out-of-pocket expenditures associated with accessing services. For designated free services, prevalence of expenditures at the service level for women and reports by financial officers of women ever having expenditures associated with services designated as free were computed. These three sources of data (desk review, surveys of women and administrators) were triangulated, and chi-square analysis was conducted to determine if charges were levied differentially by standard equity stratifiers. Designation of services as free matched what was reported in the MNCAH Policy Survey for Argentina and Ghana. In India, insecticide-treated bed nets and testing and treatment for syphilis were only designated as free for selected populations, differing from the WHO MNCAH Policy Survey. Among 1046, 923, and 1102 women and accompanying persons who were interviewed in Argentina, Ghana, and India, respectively, the highest prevalence of associated expenditures among women who received a component service in each setting was for cesarean section in Argentina (26%, 24/92); family planning in Ghana (78.4%, 69/88); and postnatal maternal care in India (94.4%, 85/90). The highest prevalence of women ever having out of pocket expenditures associated with accessing any free service reported by financial officers was 9.1% (2/22) in Argentina, 64.1% (93/145) in Ghana, and 29.7% (47/158) in India. Across the three countries, self-reports of out of pocket expenditures were significantly associated with district/province and educational status of women. Additionally, wealth quintile in Argentina and age in India were significantly associated with women reporting out of pocket expenditures. CONCLUSIONS: Free care laws were largely accurately reported in the global MNCAH policy database. Notably, we found that women absorbed both direct and indirect costs and made both formal and informal payments for services designated as free. Therefore, the policy indicator does not provide a valid reflection of UHC in the three settings.

The HIF-1α/PLOD2 axis integrates extracellular matrix organization and cell metabolism leading to aberrant musculoskeletal repair.

While hypoxic signaling has been shown to play a role in many cellular processes, its role in metabolism-linked extracellular matrix (ECM) organization and downstream processes of cell fate after musculoskeletal injury remains to be determined. Heterotopic ossification (HO) is a debilitating condition where abnormal bone formation occurs within extra-skeletal tissues. Hypoxia and hypoxia-inducible factor 1α (HIF-1α) activation have been shown to promote HO. However, the underlying molecular mechanisms by which the HIF-1α pathway in mesenchymal progenitor cells (MPCs) contributes to pathologic bone formation remain to be elucidated. Here, we used a proven mouse injury-induced HO model to investigate the role of HIF-1α on aberrant cell fate. Using single-cell RNA sequencing (scRNA-seq) and spatial transcriptomics analyses of the HO site, we found that collagen ECM organization is the most highly up-regulated biological process in MPCs. Zeugopod mesenchymal cell-specific deletion of Hif1α (Hoxa11-CreERT2; Hif1afl/fl) significantly mitigated HO in vivo. ScRNA-seq analysis of these Hoxa11-CreERT2; Hif1afl/fl mice identified the PLOD2/LOX pathway for collagen cross-linking as downstream of the HIF-1α regulation of HO. Importantly, our scRNA-seq data and mechanistic studies further uncovered that glucose metabolism in MPCs is most highly impacted by HIF-1α deletion. From a translational aspect, a pan-LOX inhibitor significantly decreased HO. A newly screened compound revealed that the inhibition of PLOD2 activity in MPCs significantly decreased osteogenic differentiation and glycolytic metabolism. This suggests that the HIF-1α/PLOD2/LOX axis linked to metabolism regulates HO-forming MPC fate. These results suggest that the HIF-1α/PLOD2/LOX pathway represents a promising strategy to mitigate HO formation.

CNTNAP4 signaling regulates osteosarcoma disease progression.

Improved treatment strategies for sarcoma rely on clarification of the molecular mediators of disease progression. Recently, we reported that the secreted glycoprotein NELL-1 modulates osteosarcoma (OS) disease progression in part via altering the sarcomatous extracellular matrix (ECM) and cell-ECM interactions. Of known NELL-1 interactor proteins, Contactin-associated protein-like 4 (Cntnap4) encodes a member of the neurexin superfamily of transmembrane molecules best known for its presynaptic functions in the central nervous system. Here, CRISPR/Cas9 gene deletion of CNTNAP4 reduced OS tumor growth, sarcoma-associated angiogenesis, and pulmonary metastases. CNTNAP4 knockout (KO) in OS tumor cells largely phenocopied the effects of NELL-1 KO, including reductions in sarcoma cell attachment, migration, and invasion. Further, CNTNAP4 KO cells were found to be unresponsive to the effects of NELL-1 treatment. Transcriptomic analysis combined with protein phospho-array demonstrated notable reductions in the MAPK/ERK signaling cascade with CNTNAP4 deletion, and the ERK1/2 agonist isoproterenol restored cell functions among CNTNAP4 KO tumor cells. Finally, human primary cells and tissues in combination with sequencing datasets confirmed the significance of CNTNAP4 signaling in human sarcomas. In summary, our findings demonstrate the biological importance of NELL-1/CNTNAP4 signaling axis in disease progression of human sarcomas and suggest that targeting the NELL-1/CNTNAP4 signaling pathway represents a strategy with potential therapeutic benefit in sarcoma patients.