Mapping of Mycobacterium tuberculosis Complex Genetic Diversity Profiles in Tanzania and Other African Countries

The aim of this study was to assess and characterize Mycobacterium tuberculosis complex (MTBC) genotypic diversity in Tanzania, as well as in neighbouring East and other several African countries. We used spoligotyping to identify a total of 293 M. tuberculosis clinical isolates (one isolate per patient) collected in the Bunda, Dar es Salaam, Ngorongoro and Serengeti areas in Tanzania. The results were compared with results in the SITVIT2 international database of the Pasteur Institute of Guadeloupe. Genotyping and phylogeographical analyses highlighted the predominance of the CAS, T, EAI, and LAM MTBC lineages in Tanzania. The three most frequent Spoligotype International Types (SITs) were: SIT21/CAS1-Kili (n = 76; 25.94%), SIT59/LAM11-ZWE (n = 22; 7.51%), and SIT126/EAI5 tentatively reclassified as EAI3-TZA (n = 18; 6.14%). Furthermore, three SITs were newly created in this study (SIT4056/EAI5 n = 2, SIT4057/T1 n = 1, and SIT4058/EAI5 n = 1). We noted that the East-African-Indian (EAI) lineage was more predominant in Bunda, the Manu lineage was more common among strains isolated in Ngorongoro, and the Central-Asian (CAS) lineage was more predominant in Dar es Salaam (p-value<0.0001). No statistically significant differences were noted when comparing HIV status of patients vs. major lineages (p-value = 0.103). However, when grouping lineages as Principal Genetic Groups (PGG), we noticed that PGG2/3 group (Haarlem, LAM, S, T, and X) was more associated with HIV-positive patients as compared to PGG1 group (Beijing, CAS, EAI, and Manu) (p-value = 0.03). This study provided mapping of MTBC genetic diversity in Tanzania (containing information on isolates from different cities) and neighbouring East African and other several African countries highlighting differences as regards to MTBC genotypic distribution between Tanzania and other African countries. This work also allowed underlining of spoligotyping patterns tentatively grouped within the newly designated EAI3-TZA lineage (remarkable by absence of spacers 2 and 3, and represented by SIT126) which seems to be specific to Tanzania. However, further genotyping information would be needed to confirm this specificity

Lifestyle physical activity among urban Palestinians and Israelis: a cross-sectional comparison in the Palestinian-Israeli Jerusalem risk factor study

<p>Abstract</p> <p>Background</p> <p>Urban Palestinians have a high incidence of coronary heart disease, and alarming prevalences of obesity (particularly among women) and diabetes. An active lifestyle can help prevent these conditions. Little is known about the physical activity (PA) behavior of Palestinians. This study aimed to determine the prevalence of insufficient PA and its socio-demographic correlates among urban Palestinians in comparison with Israelis.</p> <p>Methods</p> <p>An age-sex stratified random sample of Palestinians and Israelis aged 25-74 years living in east and west Jerusalem was drawn from the Israel National Population Registry: 970 Palestinians and 712 Israelis participated. PA in a typical week was assessed by the Multi-Ethnic Study of Atherosclerosis (MESA) questionnaire. Energy expenditure (EE), calculated in metabolic equivalents (METs), was compared between groups for moderate to vigorous-intensity physical activity (MVPA), using the Wilcoxon rank-sum test, and for domain-specific prevalence rates of meeting public health guidelines and all-domain insufficient PA. Correlates of insufficient PA were assessed by multivariable logistic modeling.</p> <p>Results</p> <p>Palestinian men had the highest median of MVPA (4740 METs-min_*wk^-1) compared to Israeli men (2,205 METs-min_*wk^-1<it>p </it>< 0.0001), or to Palestinian and Israeli women, who had similar medians (2776 METs-min_*wk^-1). Two thirds (65%) of the total MVPA reported by Palestinian women were derived from domestic chores compared to 36% in Israeli women and 25% among Palestinian and Israeli men. A high proportion (63%) of Palestinian men met the PA recommendations by occupation/domestic activity, compared to 39% of Palestinian women and 37% of the Israelis. No leisure time PA was reported by 42% and 39% of Palestinian and Israeli men (<it>p </it>= 0.337) and 53% and 28% of Palestinian and Israeli women (<it>p </it>< 0.0001). Palestinian women reported the lowest level of walking. Considering all domains, 26% of Palestinian women were classified as insufficiently active versus 13% of Palestinian men (<it>p </it>< 0.0001) who did not differ from the Israeli sample (14%). Middle-aged and elderly and less educated Palestinian women, and unemployed and pensioned Palestinian men were at particularly high risk of inactivity. Socio-economic indicators only partially explained the ethnic disparity.</p> <p>Conclusions</p> <p>Substantial proportions of Palestinian women, and subgroups of Palestinian men, are insufficiently active. Culturally appropriate intervention strategies are warranted, particularly for this vulnerable population.</p

Trends in health services utilization, medication use, and health conditions among older adults: a 2-year retrospective chart review in a primary care practice

<p>Abstract</p> <p>Background</p> <p>Population aging poses significant challenges to primary care providers and healthcare policy makers. Primary care reform can alleviate the pressures, but these initiatives require clinical benchmarks and evidence regarding utilization patterns. The objectives of this study is to measure older patients' use of health services, number of health conditions, and use of medications at the level of a primary care practice, and to investigate age- and gender-related utilization trends.</p> <p>Methods</p> <p>A cross-sectional chart audit over a 2-year study period was conducted in the academic family practice clinic of Sunnybrook Health Sciences Centre in Toronto, Ontario, Canada. All patients 65 years and older (n = 2450) were included. Main outcome measures included the number of family physician visits, specialist visits, emergency room visits, surgical admissions, diagnostic test days, inpatient hospital admissions, health conditions, and medications.</p> <p>Results</p> <p>Older patients (80-84 and 85+ age-group) had significantly more family physician visits (average of 4.4 visits per person per year), emergency room visits (average of 0.22 ER visits per year per patient), diagnostic days (average of 5.1 test days per person per year), health conditions (average of 7.7 per patient), and medications average of 8.2 medications per person). Gender differences were also observed: females had significantly more family physician visits and number of medications, while men had more specialist visits, emergency room visits, and surgical admissions. There were no gender differences for inpatient hospital admissions and number of health conditions. With the exception of the 85+ age group, we found greater intra-group variability with advancing age.</p> <p>Conclusion</p> <p>The data present a map of greater interaction with and dependency on the health care system with advancing age. The magnitudes are substantial and indicate high demands on patients and families, on professional health care providers, and on the health care system itself. There is the need to create and evaluate innovative models of care of multiple chronic conditions in the late life course.</p

Identifying postpartum intervention approaches to prevent type 2 diabetes in women with a history of gestational diabetes

<p>Abstract</p> <p>Background</p> <p>Women who develop gestational diabetes mellitus (GDM) have an increased risk for the development of type 2 diabetes. Despite this "window of opportunity," few intervention studies have targeted postpartum women with a history of GDM. We sought perspectives of women with a history of GDM to identify a) barriers and facilitators to healthy lifestyle changes postpartum, and b) specific intervention approaches that would facilitate participation in a postpartum lifestyle intervention program.</p> <p>Methods</p> <p>We used mixed methods to gather data from women with a prior history of GDM, including focus groups and informant interviews. Analysis of focus groups relied on grounded theory and used open-coding to categorize data by themes, while frequency distributions were used for the informant interviews.</p> <p>Results</p> <p>Of 38 women eligible to participate in focus groups, only ten women were able to accommodate their schedules to attend a focus group and 15 completed informant interviews by phone. We analyzed data from 25 women (mean age 35, mean pre-pregnancy BMI 28, 52% Caucasian, 20% African American, 12% Asian, 8% American Indian, 8% refused to specify). Themes from the focus groups included concern about developing type 2 diabetes, barriers to changing diet, and barriers to increasing physical activity. In one focus group, women expressed frustration about feeling judged by their physicians during their GDM pregnancy. Cited barriers to lifestyle change were identified from both methods, and included time and financial constraints, childcare duties, lack of motivation, fatigue, and obstacles at work. Informants suggested facilitators for lifestyle change, including nutrition education, accountability, exercise partners/groups, access to gyms with childcare, and home exercise equipment. All focus group and informant interview participants reported access to the internet, and the majority expressed interest in an intervention program delivered primarily via the internet that would include the opportunity to work with a lifestyle coach.</p> <p>Conclusion</p> <p>Time constraints were a major barrier. Our findings suggest that an internet-based lifestyle intervention program should be tested as a novel approach to prevent type 2 diabetes in postpartum women with a history of GDM.</p> <p>Trial Registration</p> <p>ClinicalTrials.gov: <a href="http://www.clinicaltrials.gov/ct2/show/NCT01102530">NCT01102530</a></p

Interpopulation crosses, inheritance study, and genetic variability in the brown planthopper complex, Nilaparvata lugens (Homoptera: Delphacidae)

Studies on hybridization, inheritance, and population genetics of brown planthoppers that infest rice and weeds were undertaken using starch gel electrophoresis to determine whether the weed-infesting population represents a biological race or a species. F(1) and F(2) generations were produced by crosses between parental insects from the two populations with little indication of hybrid sterility. Gpi, Mdh, and Idh loci were inherited in a simple Mendelian fashion in families of two sympatric populations. Sixteen populations of Nilaparvata spp. from eight locations were collected. The Mdh, Idh, Pgm, Gpi, 6Pgd, and Acp loci were polymorphic. The N. lugens of rice with high esterase activity were clustered into a group and characterized by the presence of alleles Gpi (110) and Gpi (120), whereas N. lugens from weeds with low esterase activity were clustered into another group and characterized by Gpi (100) and Gpi (90) . There was a lack of heterozygotes between the common alleles of the two populations. This means that the two groups of individuals belong to different gene pools

Bioavailability of Iron, Zinc, Phytate and Phytase Activity during Soaking and Germination of White Sorghum Varieties

The changes in phytate, phytase activity and in vitro bioavailability of iron and zinc during soaking and germination of three white sorghum varieties (Sorghum bicolor L. Moench), named Dorado, Shandweel-6, and Giza-15 were investigated. Sorghum varieties were soaked for 20 h and germinated for 72 h after soaking for 20 h to reduce phytate content and increase iron and zinc in vitro bioavailability. The results revealed that iron and zinc content was significantly reduced from 28.16 to 32.16% and 13.78 to 26.69% for soaking treatment and 38.43 to 39.18% and 21.80 to 31.27% for germination treatments, respectively. Phytate content was significantly reduced from 23.59 to 32.40% for soaking treatment and 24.92 to 35.27% for germination treatments, respectively. Phytase enzymes will be activated during drying in equal form in all varieties. The results proved that the main distinct point is the change of phytase activity as well as specific activity during different treatment which showed no significant differences between the varieties used. The in vitro bioavailability of iron and zinc were significantly improved as a result of soaking and germination treatments

Fas-Mediated Apoptosis Regulates the Composition of Peripheral αβ T Cell Repertoire by Constitutively Purging Out Double Negative T Cells

BACKGROUND: The Fas pathway is a major regulator of T cell homeostasis, however, the T cell population that is controlled by the Fas pathway in vivo is poorly defined. Although CD4 and CD8 single positive (SP) T cells are the two major T cell subsets in the periphery of wild type mice, the repertoire of mice bearing loss-of-function mutation in either Fas (lpr mice) or Fas ligand (gld mice) is predominated by CD4(-)CD8(-) double negative alphabeta T cells that also express B220 and generally referred to as B220+DN T cells. Despite extensive analysis, the basis of B220+DN T cell lymphoproliferation remains poorly understood. In this study we re-examined the issue of why T cell lymphoproliferation caused by gld mutation is predominated by B220+DN T cells. METHODOLOGY AND PRINCIPAL FINDINGS: We combined the following approaches to study this question: Gene transcript profiling, BrdU labeling, and apoptosis assays. Our results show that B220+DN T cells are proliferating and dying at exceptionally high rates than SP T cells in the steady state. The high proliferation rate is restricted to B220+DN T cells found in the gut epithelium whereas the high apoptosis rate occurred both in the gut epithelium and periphery. However, only in the periphery, apoptosis of B220+DN T cell is Fas-dependent. When the Fas pathway is genetically impaired, apoptosis of peripheral B220+DN T cells was reduced to a baseline level similar to that of SP T cells. Under these conditions of normalized apoptosis, B220+DN T cells progressively accumulate in the periphery, eventually resulting in B220+DN T cell lymphoproliferation. CONCLUSIONS/SIGNIFICANCE: The Fas pathway plays a critical role in regulating the tissue distribution of DN T cells through targeting and elimination of DN T cells from the periphery in the steady state. The results provide new insight into pathogenesis of DN T cell lymphoproliferation

Evaluation of Nephroprotective and Immunomodulatory Activities of Antioxidants in Combination with Cisplatin against Murine Visceral Leishmaniasis

Leishmaniasis, a neglected tropical disease (NTD) caused by Leishmania, has been put on the World Health Organization agenda for eradication as a part of their Special Programme for Tropical Diseases Research. Visceral leishmaniasis (VL) is a life-threatening disease when no treatment is given. Most of the drugs still used to treat VL are often expensive, difficult to administer, have serious side effects, and several are becoming ineffective because of increasing parasite resistance. Cisplatin is a first-generation platinum-containing drug, used in the treatment of various solid tumors. We have for the first time characterized the in vivo effect of cisplatin in murine experimental visceral leishmaniasis, but at higher doses it is nephrotoxic. Considering the above findings, the present study was designed to evaluate the protective efficacy of the drug in combination with various antioxidants to reduce or prevent cisplatin-induced nephrotoxicity. Drug treatment induces a higher secretion of Th1 cytokines, diminution in parasite burden, and the supplementation of antioxidants which are antagonists of the toxicity helps in reducing the nephrotoxicity

Clinical, genetic, epidemiologic, evolutionary, and functional delineation of TSPEAR-related autosomal recessive ectodermal dysplasia 14

TSPEAR variants cause autosomal recessive ectodermal dysplasia (ARED) 14. The function of TSPEAR is unknown. The clinical features, the mutation spectrum, and the underlying mechanisms of ARED14 are poorly understood. Combining data from new and previously published individuals established that ARED14 is primarily characterized by dental anomalies such as conical tooth cusps and hypodontia, like those seen in individuals with WNT10A-related odontoonychodermal dysplasia. AlphaFold-predicted structure-based analysis showed that most of the pathogenic TSPEAR missense variants likely destabilize the β-propeller of the protein. Analysis of 100000 Genomes Project (100KGP) data revealed multiple founder TSPEAR variants across different populations. Mutational and recombination clock analyses demonstrated that non-Finnish European founder variants likely originated around the end of the last ice age, a period of major climatic transition. Analysis of gnomAD data showed that the non-Finnish European population TSPEAR gene-carrier rate is ∼1/140, making it one of the commonest AREDs. Phylogenetic and AlphaFold structural analyses showed that TSPEAR is an ortholog of drosophila Closca, an extracellular matrix-dependent signaling regulator. We, therefore, hypothesized that TSPEAR could have a role in enamel knot, a structure that coordinates patterning of developing tooth cusps. Analysis of mouse single-cell RNA sequencing (scRNA-seq) data revealed highly restricted expression of Tspear in clusters representing enamel knots. A tspeara−/−;tspearb−/− double-knockout zebrafish model recapitulated the clinical features of ARED14 and fin regeneration abnormalities of wnt10a knockout fish, thus suggesting interaction between tspear and wnt10a. In summary, we provide insights into the role of TSPEAR in ectodermal development and the evolutionary history, epidemiology, mechanisms, and consequences of its loss of function variants

Past, present, and future of global health financing : a review of development assistance, government, out-of-pocket, and other private spending on health for 195 countries, 1995-2050

Background Comprehensive and comparable estimates of health spending in each country are a key input for health policy and planning, and are necessary to support the achievement of national and international health goals. Previous studies have tracked past and projected future health spending until 2040 and shown that, with economic development, countries tend to spend more on health per capita, with a decreasing share of spending from development assistance and out-of-pocket sources. We aimed to characterise the past, present, and predicted future of global health spending, with an emphasis on equity in spending across countries. Methods We estimated domestic health spending for 195 countries and territories from 1995 to 2016, split into three categories-government, out-of-pocket, and prepaid private health spending-and estimated development assistance for health (DAH) from 1990 to 2018. We estimated future scenarios of health spending using an ensemble of linear mixed-effects models with time series specifications to project domestic health spending from 2017 through 2050 and DAH from 2019 through 2050. Data were extracted from a broad set of sources tracking health spending and revenue, and were standardised and converted to inflation-adjusted 2018 US dollars. Incomplete or low-quality data were modelled and uncertainty was estimated, leading to a complete data series of total, government, prepaid private, and out-of-pocket health spending, and DAH. Estimates are reported in 2018 US dollars, 2018 purchasing-power parity-adjusted dollars, and as a percentage of gross domestic product. We used demographic decomposition methods to assess a set of factors associated with changes in government health spending between 1995 and 2016 and to examine evidence to support the theory of the health financing transition. We projected two alternative future scenarios based on higher government health spending to assess the potential ability of governments to generate more resources for health. Findings Between 1995 and 2016, health spending grew at a rate of 4.00% (95% uncertainty interval 3.89-4.12) annually, although it grew slower in per capita terms (2.72% [2.61-2.84]) and increased by less than $1 per capita over this period in 22 of 195 countries. The highest annual growth rates in per capita health spending were observed in upper-middle-income countries (5.55$ 8.0 trillion (7.8-8.1) in 2016 (comprising 8.6% [8.4-8.7] of the global economy and $10.3 trillion [10.1-10.6] in purchasing-power parity-adjusted dollars), with a per capita spending of US$ 5252 (5184-5319) in high-income countries, $491 (461-524) in upper-middle-income countries,$ 81 (74-89) in lower-middle-income countries, and $40 (38-43) in low-income countries. In 2016, 0.4$ 9.5 billion, 24.3% of total DAH), although spending on other infectious diseases (excluding tuberculosis and malaria) grew fastest from 2010 to 2018 (6.27% per year). The leading sources of DAH were the USA and private philanthropy (excluding corporate donations and the Bill & Melinda Gates Foundation). For the first time, we included estimates of China's contribution to DAH ($644.7 million in 2018). Globally, health spending is projected to increase to$ 15.0 trillion (14.0-16.0) by 2050 (reaching 9.4% [7.6-11.3] of the global economy and $ 21.3 trillion [19.8-23.1] in purchasing-power parity-adjusted dollars), but at a lower growth rate of 1.84% (1.68-2.02) annually, and with continuing disparities in spending between countries. In 2050, we estimate that 0.6% (0.6-0.7) of health spending will occur in currently low-income countries, despite these countries comprising an estimated 15.7% of the global population by 2050. The ratio between per capita health spending in high-income and low-income countries was 130.2 (122.9-136.9) in 2016 and is projected to remain at similar levels in 2050 (125.9 [113.7-138.1]). The decomposition analysis identified governments' increased prioritisation of the health sector and economic development as the strongest factors associated with increases in government health spending globally. Future government health spending scenarios suggest that, with greater prioritisation of the health sector and increased government spending, health spending per capita could more than double, with greater impacts in countries that currently have the lowest levels of government health spending. Interpretation Financing for global health has increased steadily over the past two decades and is projected to continue increasing in the future, although at a slower pace of growth and with persistent disparities in per-capita health spending between countries. Out-of-pocket spending is projected to remain substantial outside of high-income countries. Many low-income countries are expected to remain dependent on development assistance, although with greater government spending, larger investments in health are feasible. In the absence of sustained new investments in health, increasing efficiency in health spending is essential to meet global health targets.Peer reviewe