Effect of shock wave therapy on longitudinal bone growth and growth plate cartilage

Aim: The overall aim of this thesis was to investigate the potential for radial shock wave treatment (rSWT) to regulate growth plate chondrogenesis and longitudinal bone growth. It was based on the hypothesis that the effects are dose-dependent in a bimodal response pattern where low-energy rSWT will increase chondrocyte proliferation/hypertrophy, and thereby bone growth, while high frequency/energy rSWT will induce chondrocyte apoptosis and thereby, premature growth plate closure. Methods: To achieve this, we experimentally studied the role of rSWT in three different model systems: in vitro cultures of a mouse chondrocytic cell line, in ex vivo organ cultures of fetal rat metatarsal bones and human growth plate cartilage, as well as in vivo in rabbits. Results: A single session of high-energy rSWT was capable of locally promoting longitudinal bone growth in rat metatarsal bones cultured under normal physiological conditions. Detailed immunohistomorphometric analysis of sectioned growth plate cartilage revealed that this stimulatory effect was linked to augmented chondrocyte proliferation and hypertrophy, and decreased apoptosis. Furthermore, mechanistic studies of molecular markers governing growth plate chondrogenesis showed increased expression of PTHrP, GLI-1, NFkB, and IGF-1 in the bones exposed to rSWT (Paper I). Next, we investigated the role of rSWT in an ex vivo model of growth impairment where Hh signaling was blocked. Cultured fetal rat metatarsal bones were challenged to two different Hh inhibitors, vismodegib and GANT61, causing growth retardation, while when combined with a session of rSWT the inhibitory effects on growth plate chondrogenesis and bone growth were partially abrogated (Paper II). Thereafter, we performed in vivo studies in immature and adolescent rabbits and observed that high-energy rSWT increased the formation of chondrocyte columns and longitudinal bone growth, respectively (Paper III). Finally, mechanistic studies revealed that rSWT caused upregulation of chondrogenic genes when studied in a unique model of cultured human growth plate cartilage (SOX9, GLI-1, IHH, COL-X, and IGF-1) and also in the mouse ATDC5 chondrocytic cell line (Acan, Sox9 and, Col2a1) (Paper IV). Conclusion: Altogether, our observations, verified in preclinical and in vitro models, propose that high-energy radial shockwave treatment could potentially be used to stimulate growth plate chondrogenesis and longitudinal bone growt

Antiulcer activity of aqueous and ethanolic extracts of Ocimum sanctum leaves in albino rats

Background: Peptic ulcer is one of the most common gastrointestinal disorders and a major cause of morbidity. The incidence and prevalence of peptic ulcer has been increasing worldwide. Persisting peptic ulcer leads to complications like gastrointestinal bleeding, gastric perforation and pyloric obstruction. The complications further increase the morbidity and mortality. The objectives of this study were to evaluate the antiulcer activity of aqueous and ethanolic extracts of Ocimum sanctum leaves in albino rats.Methods: 48 apparently healthy wistar albino rats of either sex weighing about 150-200 grams were divided randomly into 12 groups (n=4). All the drugs were given as pre-treatment, per oral daily for 3 days. Test drugs, aqueous leaf extract (100 mg/kg, 200 mg/kg) and ethanolic leaf extract (50 mg/kg, 100 mg/kg) in 1% carboxymethylcellulose (CMC) were administered. Pyloric ligation and cold restrain stress were used as experimental models in the study. Parameters like free acid, gastric volume and ulcer index were observed.Results: All the test drugs significantly reduced the free acid, gastric volume and ulcer index in pyloric ligation model. 100 mg/kg of aqueous leaf extract failed to decrease the ulcer index in cold restrain stress, but other doses of test drugs reduced the ulcer index.Conclusions: Both the doses of aqueous and ethanolic extracts of Ocimum sanctum leaves exhibited significant antiulcer activity in pyloric ligation model, whereas only 200 mg/kg of aqueous leaf extract was effective in cold restrain stress model

Does pamidronate enhance the osteogenesis in mesenchymal stem cells derived from fibrous hamartoma in congenital pseudarthrosis of the tibia?

AbstractNeurofibromatosis type 1 (NF1) is a commonly occurring genetic disorder in children. Mutation in the NF1 gene has its implication in poor osteoblastic capabilities. We hypothesised that pamidronate will enhance the osteoblastic potential of the mesenchymal stem cells (MSCs) derived from lipofibromatosis tissue of children with congenital pseudarthrosis tibia (CPT) associated with NF1. In this study, bone marrow MSCs (BM MSCs) and CPT MSCs were obtained from three patients undergoing salvage surgeries/bone grafting (healthy controls) and those undergoing excision of the hamartoma and corrective surgeries respectively. The effects of pamidronate (0, 10nM, 100nM and 1μM) on cell proliferation, toxicity and differentiation potential were assessed and the outcome was measured by staining and gene expression. Our outcome showed that CPT MSCs had more proliferation rate as compared to BM MSCs. All 3 doses of pamidronate did not cause any toxicity to the cells in both the groups. The CPT MSCs showed less differentiation with pamidronate compared to the healthy control MSCs. This was quantitated by staining and gene expression analysis. Therefore, supplementation with pamidronate alone will not aid in bone formation in patients diagnosed with CPT. An additional stimulus is required to enhance bone formation

Effect of temperature and time delay in centrifugation on stability of select biomarkers of nutrition and non-communicable diseases in blood samples

Introduction: Preanalytical conditions are critical for blood sample integrity and poses challenge in surveys involving biochemical measurements. A cross sectional study was conducted to assess the stability of select biomarkers at conditions that mimic field situations in surveys. Material and methods: Blood from 420 volunteers was exposed to 2 – 8 °C, room temperature (RT), 22 – 30 °C and > 30 °C for 30 min, 6 hours, 12 hours and 24 hours prior to centrifugation. After different exposures, whole blood (N = 35) was used to assess stability of haemoglobin, HbA1c and erythrocyte folate; serum (N = 35) for assessing stability of ferritin, C-reactive protein (CRP), vitamins B12, A and D, zinc, soluble transferrin receptor (sTfR), total cholesterol, high density lipoprotein cholesterol (HDL), low density lipoprotein cholesterol (LDL), tryglicerides, albumin, total protein and creatinine; and plasma (N = 35) was used for glucose. The mean % deviation of the analytes was compared with the total change limit (TCL), computed from analytical and intra-individual imprecision. Values that were within the TCL were deemed to be stable. Result: Creatinine (mean % deviation 14.6, TCL 5.9), haemoglobin (16.4%, TCL 4.4) and folate (33.6%, TCL 22.6) were unstable after 12 hours at 22- 30°C, a temperature at which other analytes were stable. Creatinine was unstable even at RT for 12 hours (mean % deviation: 10.4). Albumin, CRP, glucose, cholesterol, LDL, triglycerides, vitamins B12 and A, sTfR and HbA1c were stable at all studied conditions. Conclusion: All analytes other than creatinine, folate and haemoglobin can be reliably estimated in blood samples exposed to 22-30°C for 12 hours in community-based studies

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

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 global, regional, and national burden of adult lip, oral, and pharyngeal cancer in 204 countries and territories:A systematic analysis for the Global Burden of Disease Study 2019

Importance Lip, oral, and pharyngeal cancers are important contributors to cancer burden worldwide, and a comprehensive evaluation of their burden globally, regionally, and nationally is crucial for effective policy planning.Objective To analyze the total and risk-attributable burden of lip and oral cavity cancer (LOC) and other pharyngeal cancer (OPC) for 204 countries and territories and by Socio-demographic Index (SDI) using 2019 Global Burden of Diseases, Injuries, and Risk Factors (GBD) Study estimates.Evidence Review The incidence, mortality, and disability-adjusted life years (DALYs) due to LOC and OPC from 1990 to 2019 were estimated using GBD 2019 methods. The GBD 2019 comparative risk assessment framework was used to estimate the proportion of deaths and DALYs for LOC and OPC attributable to smoking, tobacco, and alcohol consumption in 2019.Findings In 2019, 370 000 (95% uncertainty interval [UI], 338 000-401 000) cases and 199 000 (95% UI, 181 000-217 000) deaths for LOC and 167 000 (95% UI, 153 000-180 000) cases and 114 000 (95% UI, 103 000-126 000) deaths for OPC were estimated to occur globally, contributing 5.5 million (95% UI, 5.0-6.0 million) and 3.2 million (95% UI, 2.9-3.6 million) DALYs, respectively. From 1990 to 2019, low-middle and low SDI regions consistently showed the highest age-standardized mortality rates due to LOC and OPC, while the high SDI strata exhibited age-standardized incidence rates decreasing for LOC and increasing for OPC. Globally in 2019, smoking had the greatest contribution to risk-attributable OPC deaths for both sexes (55.8% [95% UI, 49.2%-62.0%] of all OPC deaths in male individuals and 17.4% [95% UI, 13.8%-21.2%] of all OPC deaths in female individuals). Smoking and alcohol both contributed to substantial LOC deaths globally among male individuals (42.3% [95% UI, 35.2%-48.6%] and 40.2% [95% UI, 33.3%-46.8%] of all risk-attributable cancer deaths, respectively), while chewing tobacco contributed to the greatest attributable LOC deaths among female individuals (27.6% [95% UI, 21.5%-33.8%]), driven by high risk-attributable burden in South and Southeast Asia.Conclusions and Relevance In this systematic analysis, disparities in LOC and OPC burden existed across the SDI spectrum, and a considerable percentage of burden was attributable to tobacco and alcohol use. These estimates can contribute to an understanding of the distribution and disparities in LOC and OPC burden globally and support cancer control planning efforts

Global burden of chronic respiratory diseases and risk factors, 1990–2019: an update from the Global Burden of Disease Study 2019

Background: Updated data on chronic respiratory diseases (CRDs) are vital in their prevention, control, and treatment in the path to achieving the third UN Sustainable Development Goals (SDGs), a one-third reduction in premature mortality from non-communicable diseases by 2030. We provided global, regional, and national estimates of the burden of CRDs and their attributable risks from 1990 to 2019. Methods: Using data from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019, we estimated mortality, years lived with disability, years of life lost, disability-adjusted life years (DALYs), prevalence, and incidence of CRDs, i.e. chronic obstructive pulmonary disease (COPD), asthma, pneumoconiosis, interstitial lung disease and pulmonary sarcoidosis, and other CRDs, from 1990 to 2019 by sex, age, region, and Socio-demographic Index (SDI) in 204 countries and territories. Deaths and DALYs from CRDs attributable to each risk factor were estimated according to relative risks, risk exposure, and the theoretical minimum risk exposure level input. Findings: In 2019, CRDs were the third leading cause of death responsible for 4.0 million deaths (95% uncertainty interval 3.6–4.3) with a prevalence of 454.6 million cases (417.4–499.1) globally. While the total deaths and prevalence of CRDs have increased by 28.5% and 39.8%, the age-standardised rates have dropped by 41.7% and 16.9% from 1990 to 2019, respectively. COPD, with 212.3 million (200.4–225.1) prevalent cases, was the primary cause of deaths from CRDs, accounting for 3.3 million (2.9–3.6) deaths. With 262.4 million (224.1–309.5) prevalent cases, asthma had the highest prevalence among CRDs. The age-standardised rates of all burden measures of COPD, asthma, and pneumoconiosis have reduced globally from 1990 to 2019. Nevertheless, the age-standardised rates of incidence and prevalence of interstitial lung disease and pulmonary sarcoidosis have increased throughout this period. Low- and low-middle SDI countries had the highest age-standardised death and DALYs rates while the high SDI quintile had the highest prevalence rate of CRDs. The highest deaths and DALYs from CRDs were attributed to smoking globally, followed by air pollution and occupational risks. Non-optimal temperature and high body-mass index were additional risk factors for COPD and asthma, respectively. Interpretation: Albeit the age-standardised prevalence, death, and DALYs rates of CRDs have decreased, they still cause a substantial burden and deaths worldwide. The high death and DALYs rates in low and low-middle SDI countries highlights the urgent need for improved preventive, diagnostic, and therapeutic measures. Global strategies for tobacco control, enhancing air quality, reducing occupational hazards, and fostering clean cooking fuels are crucial steps in reducing the burden of CRDs, especially in low- and lower-middle income countries

Global, regional, and national sex-specific burden and control of the HIV epidemic, 1990-2019, for 204 countries and territories: the Global Burden of Diseases Study 2019

Background: The sustainable development goals (SDGs) aim to end HIV/AIDS as a public health threat by 2030. Understanding the current state of the HIV epidemic and its change over time is essential to this effort. This study assesses the current sex-specific HIV burden in 204 countries and territories and measures progress in the control of the epidemic. Methods: To estimate age-specific and sex-specific trends in 48 of 204 countries, we extended the Estimation and Projection Package Age-Sex Model to also implement the spectrum paediatric model. We used this model in cases where age and sex specific HIV-seroprevalence surveys and antenatal care-clinic sentinel surveillance data were available. For the remaining 156 of 204 locations, we developed a cohort-incidence bias adjustment to derive incidence as a function of cause-of-death data from vital registration systems. The incidence was input to a custom Spectrum model. To assess progress, we measured the percentage change in incident cases and deaths between 2010 and 2019 (threshold >75% decline), the ratio of incident cases to number of people living with HIV (incidence-to-prevalence ratio threshold <0·03), and the ratio of incident cases to deaths (incidence-to-mortality ratio threshold <1·0). Findings: In 2019, there were 36·8 million (95% uncertainty interval [UI] 35·1–38·9) people living with HIV worldwide. There were 0·84 males (95% UI 0·78–0·91) per female living with HIV in 2019, 0·99 male infections (0·91–1·10) for every female infection, and 1·02 male deaths (0·95–1·10) per female death. Global progress in incident cases and deaths between 2010 and 2019 was driven by sub-Saharan Africa (with a 28·52% decrease in incident cases, 95% UI 19·58–35·43, and a 39·66% decrease in deaths, 36·49–42·36). Elsewhere, the incidence remained stable or increased, whereas deaths generally decreased. In 2019, the global incidence-to-prevalence ratio was 0·05 (95% UI 0·05–0·06) and the global incidence-to-mortality ratio was 1·94 (1·76–2·12). No regions met suggested thresholds for progress. Interpretation: Sub-Saharan Africa had both the highest HIV burden and the greatest progress between 1990 and 2019. The number of incident cases and deaths in males and females approached parity in 2019, although there remained more females with HIV than males with HIV. Globally, the HIV epidemic is far from the UNAIDS benchmarks on progress metrics. Funding: The Bill & Melinda Gates Foundation, the National Institute of Mental Health of the US National Institutes of Health (NIH), and the National Institute on Aging of the NIH

Measuring routine childhood vaccination coverage in 204 countries and territories, 1980-2019 : a systematic analysis for the Global Burden of Disease Study 2020, Release 1

Background Measuring routine childhood vaccination is crucial to inform global vaccine policies and programme implementation, and to track progress towards targets set by the Global Vaccine Action Plan (GVAP) and Immunization Agenda 2030. Robust estimates of routine vaccine coverage are needed to identify past successes and persistent vulnerabilities. Drawing from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2020, Release 1, we did a systematic analysis of global, regional, and national vaccine coverage trends using a statistical framework, by vaccine and over time. Methods For this analysis we collated 55 326 country-specific, cohort-specific, year-specific, vaccine-specific, and dosespecific observations of routine childhood vaccination coverage between 1980 and 2019. Using spatiotemporal Gaussian process regression, we produced location-specific and year-specific estimates of 11 routine childhood vaccine coverage indicators for 204 countries and territories from 1980 to 2019, adjusting for biases in countryreported data and reflecting reported stockouts and supply disruptions. We analysed global and regional trends in coverage and numbers of zero-dose children (defined as those who never received a diphtheria-tetanus-pertussis [DTP] vaccine dose), progress towards GVAP targets, and the relationship between vaccine coverage and sociodemographic development. Findings By 2019, global coverage of third-dose DTP (DTP3; 81.6% [95% uncertainty interval 80.4-82 .7]) more than doubled from levels estimated in 1980 (39.9% [37.5-42.1]), as did global coverage of the first-dose measles-containing vaccine (MCV1; from 38.5% [35.4-41.3] in 1980 to 83.6% [82.3-84.8] in 2019). Third- dose polio vaccine (Pol3) coverage also increased, from 42.6% (41.4-44.1) in 1980 to 79.8% (78.4-81.1) in 2019, and global coverage of newer vaccines increased rapidly between 2000 and 2019. The global number of zero-dose children fell by nearly 75% between 1980 and 2019, from 56.8 million (52.6-60. 9) to 14.5 million (13.4-15.9). However, over the past decade, global vaccine coverage broadly plateaued; 94 countries and territories recorded decreasing DTP3 coverage since 2010. Only 11 countries and territories were estimated to have reached the national GVAP target of at least 90% coverage for all assessed vaccines in 2019. Interpretation After achieving large gains in childhood vaccine coverage worldwide, in much of the world this progress was stalled or reversed from 2010 to 2019. These findings underscore the importance of revisiting routine immunisation strategies and programmatic approaches, recentring service delivery around equity and underserved populations. Strengthening vaccine data and monitoring systems is crucial to these pursuits, now and through to 2030, to ensure that all children have access to, and can benefit from, lifesaving vaccines. Copyright (C) 2021 The Author(s). Published by Elsevier Ltd.Peer reviewe