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.

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.

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.

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.

TrkA-mediated sensory innervation of injured mouse tendon supports tendon sheath progenitor cell expansion and tendon repair.

Peripheral neurons terminate at the surface of tendons partly to relay nociceptive pain signals; however, the role of peripheral nerves in tendon injury and repair remains unclear. Here, we show that after Achilles tendon injury in mice, there is new nerve growth near tendon cells that express nerve growth factor (NGF). Conditional deletion of the Ngf gene in either myeloid or mesenchymal mouse cells limited both innervation and tendon repair. Similarly, inhibition of the NGF receptor tropomyosin receptor kinase A (TrkA) abrogated tendon healing in mouse tendon injury. Sural nerve transection blocked the postinjury increase in tendon sensory innervation and the expansion of tendon sheath progenitor cells (TSPCs) expressing tubulin polymerization promoting protein family member 3. Single cell and spatial transcriptomics revealed that disruption of sensory innervation resulted in dysregulated inflammatory signaling and transforming growth factor-ß (TGFß) signaling in injured mouse tendon. Culture of mouse TSPCs with conditioned medium from dorsal root ganglia neuron further supported a role for neuronal mediators and TGFß signaling in TSPC proliferation. Transcriptomic and histologic analyses of injured human tendon biopsy samples supported a role for innervation and TGFß signaling in human tendon regeneration. Last, treating mice after tendon injury systemically with a small-molecule partial agonist of TrkA increased neurovascular response, TGFß signaling, TSPC expansion, and tendon tissue repair. Although further studies should investigate the potential effects of denervation on mechanical loading of tendon, our results suggest that peripheral innervation is critical for the regenerative response after acute tendon injury.

Validation of a measure to assess decision-making autonomy in family planning services in three low- and middle-income countries: The Family Planning Autonomous Decision-Making scale (FP-ADM).

BACKGROUND: Integrating measures of respectful care is an important priority in family planning programs, aligned with maternal health efforts. Ensuring women can make autonomous reproductive health decisions is an important indicator of respectful care. While scales have been developed and validated in family planning for dimensions of person-centered care, none focus specifically on decision-making autonomy. The Mothers Autonomy in Decision-Making (MADM) scale measures autonomy in decision-making during maternity care. We adapted the MADM scale to measure autonomy surrounding a woman's decision to use a contraceptive method within the context of contraceptive counselling. This study presents a psychometric validation of the Family Planning Autonomous Decision-Making (FP-ADM) scale using data from Argentina, Ghana, and India. METHODS AND FINDINGS: We used cross-sectional data from women in four subnational areas in Argentina (n = 890), Ghana (n = 1,114), and India (n = 1,130). In each area, 20 primary sampling units (PSUs) were randomly selected based on probability proportional to size. Households were randomly selected in Ghana and India. In Argentina, all facilities providing reproductive and maternal health services within selected PSUs were included and women were randomly selected upon exiting the facility. Interviews were conducted with a sample of 360 women per district. In total, 890 women completed the FP-ADM in Argentina, 1,114 in Ghana and 1,130 in India. To measure autonomous decision-making within FP service delivery, we adapted the items of the MADM scale to focus on family planning. To assess the scale's psychometric properties, we first examined the eigenvalues and conducted a parallel analysis to determine the number of factors. We then conducted exploratory factor analysis to determine which items to retain. The resulting factors were then identified based on the corresponding items. Internal consistency reliability was assessed with Cronbach's alpha. We assessed both convergent and divergent construct validity by examining associations with expected outcomes related to the underlying construct. The Eigenvalues and parallel analysis suggested a two-factor solution. The two underlying dimensions of the construct were identified as "Bidirectional Exchange of Information" (Factor 1) and "Empowered Choice" (Factor 2). Cronbach's alpha was calculated for the full scale and each subscale. Results suggested good internal consistency of the scale. There was a strong, significant positive association between whether a woman expressed satisfaction with quality of care received from the healthcare provider and her FP-ADM score in all three countries and a significant negative association between a woman's FP-ADM score and her stated desire to switch contraceptive methods in the future. CONCLUSIONS: Our results suggest the FP-ADM is a valid instrument to assess decision-making autonomy in contraceptive counseling and service delivery in diverse low- and middle-income countries. The scale evidenced strong construct, convergent, and divergent validity and high internal consistency reliability. Use of the FP-ADM scale could contribute to improved measurement of person-centered family planning services.

Validating indicators for monitoring availability and geographic distribution of emergency obstetric and newborn care (EmoNC) facilities: A study triangulating health system, facility, and geospatial data.

Availability of emergency obstetric and newborn care (EmONC) is a strong supply side measure of essential health system capacity that is closely and causally linked to maternal mortality reduction and fundamentally to achieving universal health coverage. The World Health Organization's indicator "Availability of EmONC facilities" was prioritized as a core indicator to prevent maternal death. The indicator focuses on whether there are sufficient emergency care facilities to meet the population need, but not all facilities designated as providing EmONC function as such. This study seeks to validate "Availability of EmONC" by comparing the value of the indicator after accounting for key aspects of facility functionality and an alternative measure of geographic distribution. This study takes place in four subnational geographic areas in Argentina, Ghana, and India using a census of all birthing facilities. Performance of EmONC in the 90 days prior to data collection was assessed by examining facility records. Data were collected on facility operating hours, staffing, and availability of essential medications. Population estimates were generated using ArcGIS software using WorldPop to estimate the total population, and the number of women of reproductive age (WRA), pregnancies and births in the study areas. In addition, we estimated the population within two-hours travel time of an EmONC facility by incorporating data on terrain from Open Street Map. Using these data sources, we calculated and compared the value of the indicator after incorporating data on facility performance and functionality while varying the reference population used. Further, we compared its value to the proportion of the population within two-hours travel time of an EmONC facility. Included in our study were 34 birthing facilities in Argentina, 51 in Ghana, and 282 in India. Facility performance of basic EmONC (BEmONC) and comprehensive EmONC (CEmONC) signal functions varied considerably. One facility (4.8%) in Ghana and no facility in India designated as BEmONC had performed all seven BEmONC signal functions. In Argentina, three (8.8%) CEmONC-designated facilities performed all nine CEmONC signal functions, all located in Buenos Aires Region V. Four CEmONC-designated facilities in Ghana (57.1%) and the three CEmONC-designated facilities in India (23.1%) evidenced full CEmONC performance. No sub-national study area in Argentina or India reached the target of 5 BEmONC-level facilities per 20,000 births after incorporating facility functionality yet 100% did in Argentina and 50% did in India when considering only facility designation. Demographic differences also accounted for important variation in the indicator's value. In Ghana, the total population in Tolon within 2 hours travel time of a designated EmONC facility was estimated at 99.6%; however, only 91.1% of women of reproductive age were within 2 hours travel time. Comparing the value of the indicator when calculated using different definitions reveals important inconsistencies, resulting in conflicting information about whether the threshold for sufficient coverage is met. This raises important questions related to the indicator's validity. To provide a valid measure of effective coverage of EmONC, the construct for measurement should extend beyond the most narrow definition of availability and account for functionality and geographic accessibility.

Validating midwifery professionals' scope of practice and competency: A multi-country study comparing national data to international standards.

BACKGROUND: There is a global shortage of midwives, whose services are essential to meet the healthcare needs of pregnant women and newborns. Evidence suggests that if enough midwives, trained and regulated to global standards, were deployed worldwide, maternal, and perinatal mortality would decline significantly. Health workforce planning estimates the number of midwives needed to achieve population coverage of midwifery interventions. However, to provide a valid measure of midwifery care coverage, an indicator must consider not only the raw number of midwives, but also their scope and competency. The tasks midwives are authorized to deliver and their competency to perform essential skills and behaviors provide crucial information for understanding the availability of safe, high-quality midwifery services. Without reliable estimates for an adequate midwifery workforce, progress toward ending preventable maternal and perinatal mortality will continue to be uneven. The International Labor Organization (ILO) and the International Confederation of Midwives (ICM) suggest standards for midwifery scope of practice and competencies. This paper compares national midwifery regulations, scope, and competencies in three countries to the ILO and ICM standards to validate measures of midwife density. We also assess midwives' self-reported skills/behaviors from the ICM competencies and their acquisition. METHODS AND FINDINGS: We compared midwives' scope of practice in Argentina, Ghana, and India to the ILO Tasks and ICM Essential Competencies for Midwifery Practice. We compared midwives self-reported skills/behaviors with the ICM Competencies. Univariate and bivariate analysis was conducted to describe the association between midwives' skills and selected characteristics. National scopes of practice matched two ILO tasks in Argentina, four in India, and all in Ghana. National standards partially reflected ICM skills in Categories 2, 3, and 4 (pre-pregnancy and antenatal care; care during labor and birth; and ongoing care of women and newborns, respectively) in Argentina (range 11% to 67%), mostly in India (range 74% to 100%) and completely in Ghana (100% match). 1,266 midwives surveyed reported considerable variation in competency for skills and behaviors across ICM Category 2, 3, and 4. Most midwives reported matching skills and behaviors around labor and childbirth (Category 2). Higher proportions of midwives reported gaining basic skills through in-service training and on-job-experience than in pre-service training. CONCLUSION: Estimating the density of midwives needed for an adequate midwifery workforce capable of providing effective population coverage is predicated on a valid numerator. A reliable and valid count of midwives to meet population needs assumes that each midwife counted has the authority to exercise the same behaviors and reflects the ability to perform them with comparable competency. Our results demonstrate variation in midwifery scopes of practice and self-reported competencies in comparison to global standards that pose a threat to the reliability and validity of the numerator in measures of midwife density, and suggest the potential for expanded authorization and improved education and training to meet global reference standards for midwifery practice has not been fully realized. Although the universally recognized standard, this study demonstrates that the complex, composite descriptions of skills and behaviors in the ICM competencies make them difficult to use as benchmark measures with any precision, as they are not defined or structured to serve as valid measures for assessing workforce competency. A simplified, content-validated measurement system is needed to facilitate evaluation of the competency of the midwifery workforce.

Authorization of midwives to perform basic emergency obstetric and newborn care signal functions in Argentina, Ghana, and India: A multi-country validation study of a key global maternal and newborn health indicator.

BACKGROUND: Midwives' authorization to deliver the seven basic emergency obstetric and newborn care (BEmONC) functions is a core policy indicator in global monitoring frameworks, yet little evidence supports whether such data are captured accurately, or whether authorization demonstrates convergence with midwives' skills and actual provision of services. In this study, we aimed to validate the data reported in global monitoring frameworks (criterion validity) and to determine whether a measure of authorization is a valid indicator for BEmONC availability (construct validity). METHODS: We conducted a validation study in Argentina, Ghana, and India. To assess accuracy of the reported data on midwives' authorization to provide BEmONC services, we reviewed national regulatory documents and compared with reported country-specific data in Countdown to 2030 and the World Health Organization Maternal, Newborn, Child and Adolescent Health Policy Survey. To assess whether authorization demonstrates convergent validity with midwives' skills, training, and performance of BEmONC signal functions, we surveyed 1257 midwives/midwifery professionals and assessed variance. RESULTS: We detected discrepancies between data reported in the global monitoring frameworks and the national regulatory framework in all three countries. We found wide variations between midwives' authorization to perform signal functions and their self-reported skills and actual performance within the past 90 days. The percentage of midwives who reported performing all signal functions for which they were authorized per country-specific regulations was 17% in Argentina, 23% in Ghana, and 31% in India. Additionally, midwives in all three countries reported performing some signal functions that the national regulations did not authorize. CONCLUSION: Our findings suggest limitations in criterion and construct validity for this indicator in Argentina, Ghana, and India. Some signal functions such as assisted vaginal delivery may be obsolete based on current practice patterns. Findings suggest the need to re-examine the emergency interventions that should be included as BEmONC signal functions.

Measuring adequacy of the midwifery workforce using standards of competency and scope of work: Exploring the density and distribution of midwives in three low- and middle-income countries using cross-sectional and geospatial data.

BACKGROUND: A global midwifery shortage hampers the goal of ending preventable maternal/newborn mortality and stillbirths. Whether current measures of midwifery workforce adequacy are valid is unknown. We compare two measures of density and distribution of midwifery professionals to assess their consistency, and explore how incorporating midwifery scope, competency, and the adjusting reference population impacts this critical metric. METHODS AND FINDINGS: We collected a census of midwives employed in eligible facilities in our study settings, (422 in Ghana; 909 in India), assessed the number practicing within the scope of work for midwifery professionals defined in the International Labor Organization International Standard Classification of Occupations, and whether they reported possessing the ICM essential competencies for basic midwifery practice. We altered the numerator, iteratively narrowing it from a simple count to include data on scope of practice and competency and reported changes in value. We altered the denominator by calculating the number of midwives per 10,000 total population, women of reproductive age, pregnancies, and births and explored variation in the indicator. Across four districts in Ghana, density of midwives decreased from 8.59/10,000 total population when counting midwives from facility staffing rosters to 1.30/10,000 total population when including only fully competent midwives by the ICM standard. In India, no midwives met the standard, thus the midwifery density of 1.37/10,000 total population from staffing rosters reduced to 0.00 considering competency. Changing the denominator to births vastly altered subnational measures, ranging from ~1700% change in Tolon to ~8700% in Thiruvallur. CONCLUSION: Our study shows that varying underlying parameters significantly affects the value of the estimate. Factoring in competency greatly impacts the effective coverage of midwifery professionals. Disproportionate differences were noted when need was estimated based on total population versus births. Future research should compare various estimates of midwifery density to health system process and outcome measures.

Prevalence and Correlates of Vitamin D Deficiency Among Children and Adolescents From a Nationally Representative Survey in India.

OBJECTIVE: To evaluate the prevalence of vitamin D deficiency (VDD) and its correlates among apparently healthy children and adolescents. METHODS: We carried out a secondary analysis of data of Comprehensive National Nutrition Survey 2016-18 to analyze the pre-valence and predictors of VDD among Indian children and adolescents. RESULTS: The over-all prevalence of VDD in preschool children (1-4 years), school age (5-9 years) children, and adolescents (10-19 years) was 13.7%, 18.2%, and 23.9%, respectively. Age, living in urban area, and winter season were significantly associated with VDD. Vegetarian diet and high-income households were the main risk factors observed in 5-19 years age category. Female sex and less than three hour of physical activity/week were independent risk factors among adolescents. CONCLUSION: The prevalence and determinants of VDD across different age-groups are reported, and these should be interpreted and addressed to decrease the burden of VDD in India.

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.

Improving measures of access to legal abortion: A validation study triangulating multiple data sources to assess a global indicator.

BACKGROUND: Global mechanisms have been established to monitor and facilitate state accountability regarding the legal status of abortion. However, there is little evidence describing whether these mechanisms capture accurate data. Moreover, it is uncertain whether the "legal status of abortion" is a valid proxy measure for access to safe abortion, pursuant to the global goals of reducing preventable maternal mortality and advancing reproductive rights. Therefore, this study sought to assess the accuracy of reported monitoring data, and to determine whether evidence supports the consistent application of domestic law by health care professionals such that legality of abortion functions as a valid indicator of access. METHODS AND FINDINGS: We conducted a validation study using three countries as illustrative case examples: Argentina, Ghana, and India. We compared data reported by two global monitoring mechanisms (Countdown to 2030 and the Global Abortion Policies Database) against domestic source documents collected through in-depth policy review. We then surveyed health care professionals authorized to perform abortions about their knowledge of abortion law in their countries and their personal attitudes and practices regarding provision of legal abortion. We compared professionals' responses to the domestic legal frameworks described in the source documents to establish whether professionals consistently applied the law as written. This analysis revealed weaknesses in the criterion validity and construct validity of the "legal status of abortion" indicator. We detected discrepancies between data reported by the global monitoring and accountability mechanisms and the domestic policy reviews, even though all referenced the same source documents. Further, provider surveys unearthed important context-specific barriers to legal abortion not captured by the indicator, including conscientious objection and imposition of restrictions at the provider's discretion. CONCLUSIONS: Taken together, these findings denote weaknesses in the indicator "legal status of abortion" as a proxy for access to safe abortion, as well as inaccuracies in data reported to global monitoring mechanisms. This information provides important groundwork for strengthening indicators for monitoring access to abortion and for renewed advocacy to assure abortion rights worldwide.

Quality of anthropometric data in India's National Family Health Survey: Disentangling interviewer and area effect using a cross-classified multilevel model.

India has adopted a target-based approach to reduce the scourge of child malnourishment. Because the monitoring and evaluation required by this approach relies primarily on large-scale data, a data quality assessment is essential. As field teams are the primary mode of data collection in large-scale surveys, this study attempts to understand their contribution to variations in child anthropometric measures. This research can help disentangle the confounding effects of regions/districts and field teams on the quality of child anthropometric data. The anthropometric z-scores of 2,25,002 children below five years were obtained from the fourth round of India's National Family and Health Survey (NFHS-4), 2015-16. Unadjusted and adjusted standard deviations (SD) of the anthropometric measures were estimated to assess the variations in measurements. In addition, a cross-classified multilevel model (CCMM) approach was adopted to estimate the contribution of geographical regions/districts and teams to variations in anthropometric measures. The unadjusted SDs of the measures of stunting, wasting, and underweight were 1.7, 1.4, and 1.2, respectively. The SD of stunting was above the World Health Organisation threshold (0.8-1.2), as well as the Demographic and Health Survey mark. After adjusting for team-level characteristics, the SDs of all three measures reduced marginally, indicating that team-level workload had a marginal but significant role in explaining the variations in anthropometric z-scores. The CCMM showed that the maximum contribution to variations in anthropometric z-scores came from community-level (Primary Sampling Unit (PSU)) characteristics. Team-level characteristics had a higher contribution to variations in anthropometric z-scores than district-level attributes. Variations in measurement were higher for child height than weight. The present study decomposes the effects of district- and team-level factors and highlights the nuances of introducing teams as a level of analysis in multilevel modelling. Population size, density, and terrain variations between PSUs should be considered when allocating field teams in large-scale surveys.

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.

Neuron-to-vessel signaling is a required feature of aberrant stem cell commitment after soft tissue trauma.

The functional interdependence of nerves and blood vessels is a well-established concept during tissue morphogenesis, yet the role of neurovascular coupling in proper and aberrant tissue repair is an emerging field of interest. Here, we sought to define the regulatory relationship of peripheral nerves on vasculature in a severe extremity trauma model in mice, which results in aberrant cell fate and heterotopic ossification (HO). First, a high spatial degree of neurovascular congruency was observed to exist within extremity injury associated heterotopic ossification. Vascular and perivascular cells demonstrate characteristic responses to injury, as assessed by single cell RNA sequencing. This vascular response to injury was blunted in neurectomized mice, including a decrease in endothelial proliferation and type H vessel formation, and a downregulation of key transcriptional networks associated with angiogenesis. Independent mechanisms to chemically or genetically inhibit axonal ingrowth led to similar deficits in HO site angiogenesis, a reduction in type H vessels, and heterotopic bone formation. Finally, a combination of single cell transcriptomic approaches within the dorsal root ganglia identified key neural-derived angiogenic paracrine factors that may mediate neuron-to-vascular signaling in HO. These data provide further understanding of nerve-to-vessel crosstalk in traumatized soft tissues, which may reflect a key determinant of mesenchymal progenitor cell fate after injury.

Multisite, mixed methods study to validate 10 maternal health system and policy indicators in Argentina, Ghana and India: a research protocol.

INTRODUCTION: Most efforts to assess maternal health indicator validity focus on measures of service coverage. Fewer measures focus on the upstream enabling environment, and such measures are typically not research validated. Thus, methods for validating system and policy-level indicators are not well described. This protocol describes original multicountry research to be conducted in Argentina, Ghana and India, to validate 10 indicators from the monitoring framework for the 'Strategies toward Ending Preventable Maternal Mortality' (EPMM). The overall aim is to improve capacity to drive and track progress towards achieving the priority recommendations in the EPMM strategies. This work is expected to contribute new knowledge on validation methodology and reveal important information about the indicators under study and the phenomena they target for monitoring. Validating the indicators in three diverse settings will explore the external validity of results. METHODS AND ANALYSIS: This observational study explores the validity of 10 indicators from the EPMM monitoring framework via seven discrete validation exercises that will use mixed methods: (1) cross-sectional review of policy data, (2) retrospective review of facility-level patient and administrative data and (3) collection of primary quantitative and qualitative cross-sectional data from health service providers and clients. There is a specific methodological approach and analytic plan for each indicator, directed by unique, relevant validation research questions. ETHICS AND DISSEMINATION: The protocol was approved by the Office of Human Research Administration at Harvard University in November 2019. Individual study sites received approval via local institutional review boards by January 2020 except La Pampa, Argentina, approved June 2020. Our dissemination plan enables unrestricted access and reuse of all published research, including data sets. We expect to publish at least one peer-reviewed publication per validation exercise. We will disseminate results at conferences and engage local stakeholders in dissemination activities in each study country.

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.

Radial shockwave treatment promotes chondrogenesis in human growth plate and longitudinal bone growth in rabbits.

OBJECTIVE: The process of longitudinal bone growth occurs at the growth plate where the chondrocytes undergo apparent structural and molecular changes to promote growth. Recent reports suggest that radial shockwave treatment (rSWT) stimulates bone length in cultured fetal rat metatarsals. Therefore, we investigated if rSWT has similar growth promoting effects on cultured human growth plate fragments and addressed the same in a preclinical in vivo rabbit model by subjecting their growth plates to rSWT. METHODS: Short-term effects of high-energy rSWT were evaluated in a unique model of cultured human growth plate cartilage (n = 5) wherein samples exposed to rSWT were assessed for chondrogenic markers at 24 h in comparison to unexposed samples obtained from the same limb. Local in vivo effects were studied in six-week-old rabbits who had their distal femurs exposed to four weekly sessions of rSWT at low- and high-energy levels (n = 4 each). At sacrifice, histomorphometric and immunohistochemistry analyses were performed. For effect on longitudinal growth, proximal tibiae of 22-week-old rabbits (n = 12) were asymmetrically exposed to rSWT; the contralateral side served as untreated controls. At sacrifice, the final bone length was measured. RESULTS: In the ex vivo model of cultured human growth plate cartilage, rSWT exposure upregulated SOX9 and COL2A1 compared to control. In the immature rabbit model, an increased number of proliferative chondrocytes and column density was seen for both the energy levels. In the adolescent rabbits, an increase in tibial length was observed after the fourth session of high-energy rSWT and until six-weeks after rSWT compared to the untreated limb. CONCLUSIONS: Our preliminary experimental results suggest that rSWT may serve as a non-invasive treatment and possibly a safe strategy to stimulate longitudinal bone growth. However, further studies are needed to assess the in vivo effects of rSWT in models of disturbed bone growth.

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.