3D Traction Force Microscopy in Biological Gels: From Single Cells to Multicellular Spheroids.

Cell traction force plays a critical role in directing cellular functions, such as proliferation, migration, and differentiation. Current understanding of cell traction force is largely derived from 2D measurements where cells are plated on 2D substrates. However, 2D measurements do not recapitulate a vital aspect of living systems; that is, cells actively remodel their surrounding extracellular matrix (ECM), and the remodeled ECM, in return, can have a profound impact on cell phenotype and traction force generation. This reciprocal adaptivity of living systems is encoded in the material properties of biological gels. In this review, we summarize recent progress in measuring cell traction force for cells embedded within 3D biological gels, with an emphasis on cell-ECM cross talk. We also provide perspectives on tools and techniques that could be adapted to measure cell traction force in complex biochemical and biophysical environments.

Characterization and synergy studies of Caudoviricete Escherichia phage FS2B infecting multi-drug resistant uropathogenic Escherichia coli isolates.

Escherichia coli is one of the most common causes of urinary tract infections. However, a recent upsurge in antibiotic resistance among uropathogenic E. coli (UPEC) strains has provided an impetus to explore alternative antibacterial compounds to encounter this major issue. In this study, a lytic phage against multi-drug-resistant (MDR) UPEC strains was isolated and characterized. The isolated Escherichia phage FS2B of class Caudoviricetes exhibited high lytic activity, high burst size, and a small adsorption and latent time. The phage also exhibited a broad host range and inactivated 69.8% of the collected clinical, and 64.8% of the identified MDR UPEC strains. Further, whole genome sequencing revealed that the phage was 77,407 bp long, having a dsDNA with 124 coding regions. Annotation studies confirmed that the phage carried all the genes associated with lytic life cycle and all lysogeny related genes were absent in the genome. Further, synergism studies of the phage FS2B with antibiotics demonstrated a positive synergistic association among them. The present study therefore concluded that the phage FS2B possesses an immense potential to serve as a novel candidate for treatment of MDR UPEC strains.

Perception of Threat and Efficacy in Contracting COVID-19 Infection among Tobacco Users - A Cross-sectional Analytical Study from Four Indian States.

BACKGROUND: To trigger quit intention and practice of preventive measures for COVID-19 among tobacco users; it is imperative for them to be well aware of the fact that they are at higher risk of COVID-19 infection and should be at higher efficacy to practice preventive measures for the disease as compared to nonusers of tobacco. OBJECTIVES: This community-based cross-sectional analytical study was conducted from April 2020 to May 2020 among 1203 adult participants to compare the threat and efficacy perception among users and nonusers of tobacco. MATERIALS AND METHODS: Perception of threat was assessed using three questions on perceived threat and one question on perceived susceptibility; whereas perception of efficacy was assessed using four questions each on self-efficacy and response efficacy through telephonic interview. RESULTS: There was no significant difference in the overall threat perception among users and nonusers of tobacco. However, state-wise analysis showed that tobacco users had higher perception of threat for SARS-CoV-2 infection in all the states except Telangana. The overall perception of efficacy among tobacco users was significantly higher as compared to nonusers of tobacco. CONCLUSION: The study calls for active collaboration between tobacco control enthusiasts and the Government to promote awareness of a higher risk of COVID-19 disease among tobacco users. In essence, the study's implications extend beyond COVID-19 and can guide targeted efforts to promote awareness, behavior change, and collaboration in the context of other infectious diseases among tobacco users.

Association between child marriage and institutional delivery care services use in Bangladesh: intersections between education and place of residence.

OBJECTIVES: To examine the association between child marriage and women's use of institutional delivery care services and whether education and place of residence moderate this association. STUDY DESIGN: The study used de-identified data from four rounds (2004, 2007, 2011, and 2014) of the Bangladesh Demographic and Health Survey (BDHS). The BDHS is a cross-sectional survey conducted every three years. The analysis was based on 16,099 ever-married women aged 15-49 years with at least one live birth in the three years before the survey. METHODS: The study used multivariable logistic regression models with interaction terms between age at marriage, education, and place of residence. Adjusted predicted probabilities of outcome variables were computed from interaction models. RESULTS: Child marriage is significantly associated with decreased use of institutional delivery care services. Compared to women who married at adult ages (≥18 years), women who married between ages of 12-14 years were the most disadvantaged in having delivered at a health facility (odds ratio [OR]: 0.62; 95% confidence interval [CI]: 0.51-0.74) and having a skilled attendant present (OR: 0.63; 95% CI: 0.53-0.75) at the birth of their last child. The analysis suggests that the effect of education on the use of institutional delivery care is stronger among women married at age 18 or older compared to women who married younger than age 18 years. Further, the joint effect of age at marriage and education is stronger for women living in urban than rural place of residence. CONCLUSIONS: Increasing the age at marriage and discouraging child marriage may be a fruitful way to improve mother and child health in Bangladesh. Encouraging girls to complete high school and pursue college education would also help decline the rate of child marriage and, in turn, benefit social mobility and health.

Obesity challenges the hepatoprotective function of the integrated stress response to asparaginase exposure in mice.

Obesity increases risk for liver toxicity by the anti-leukemic agent asparaginase, but the mechanism is unknown. Asparaginase activates the integrated stress response (ISR) via sensing amino acid depletion by the eukaryotic initiation factor 2 (eIF2) kinase GCN2. The goal of this work was to discern the impact of obesity, alone versus alongside genetic disruption of the ISR, on mechanisms of liver protection during chronic asparaginase exposure in mice. Following diet-induced obesity, biochemical analysis of livers revealed that asparaginase provoked hepatic steatosis that coincided with activation of another eIF2 kinase PKR-like endoplasmic reticulum kinase (PERK), a major ISR transducer to ER stress. Genetic loss of Gcn2 intensified hepatic PERK activation to asparaginase, yet surprisingly, mRNA levels of key ISR gene targets such as Atf5 and Trib3 failed to increase. Instead, mechanistic target of rapamycin complex 1 (mTORC1) signal transduction was unleashed, and this coincided with liver dysfunction reflected by a failure to maintain hydrogen sulfide production or apolipoprotein B100 (ApoB100) expression. In contrast, obese mice lacking hepatic activating transcription factor 4 (Atf4) showed an exaggerated ISR and greater loss of endogenous hydrogen sulfide but normal inhibition of mTORC1 and maintenance of ApoB100 during asparaginase exposure. In both genetic mouse models, expression and phosphorylation of Sestrin2, an ATF4 gene target, was increased by asparaginase, suggesting mTORC1 inhibition during asparaginase exposure is not driven via eIF2-ATF4-Sestrin2. In conclusion, obesity promotes a maladaptive ISR during asparaginase exposure. GCN2 functions to repress mTORC1 activity and maintain ApoB100 protein levels independently of Atf4 expression, whereas hydrogen sulfide production is promoted via GCN2-ATF4 pathway.

Evaluation of Cast Re-Orientation on a Dental Surveyor Using Three Tripod Techniques: A Survey and In Vitro Study.

PURPOSE: To survey different educational levels (i.e., students, interns, technicians, and prosthodontic faculty) with regard to their opinions, attitudes, and adoption of three selected tripod techniques. The study will also investigate the accuracy of these techniques to reposition casts on the dental surveyor in anterio-posterior (AP) and lateral directions at both technique and educational levels. MATERIALS AND METHODS: Tripod points, scored lines, and cemented post tripod techniques were used in this study. Three Kennedy class II modification I stone casts, duplicated from a standard cast, were assigned to each of the tripod techniques. The tilt angles of all casts were set on the dental surveyor to 10° (control angle) in AP and lateral directions using a digital angle gauge with an accuracy of 0.2°. The casts were tripoded accordingly. A total of 243 participants were involved in this study. Participants were first asked to remount the three casts on three different dental surveyors using the tripod technique noted on each cast. Questionnaires were then given to each participant in an individual interview setting; this assured a 100% response rate. The angle differences were calculated. All data were coded and entered into an Excel Spreadsheet file. Statistical analyses were performed using a paired Chi-square, Wilcoxon Matched-pairs, ANOVA, and Tukey post hoc tests at 5% level of significance. RESULTS: No significant difference was found between the educational levels relative to the responses to technique demands, sensitivity, and time required for reorientation (p = 0.08202, 0.8108, 0.6874, respectively); however, the majority of respondents reported low technique demands, low sensitivity, and time saving for technique C in comparison to techniques A and B. Significant differences were noted among the educational levels in response to preference and adoption questions (p = 0.0035 and 0.0015, respectively). The highest percentage of faculty chose technique A for inclusion into the academic curriculum. Wilcoxon Matched-pairs test revealed that technique C was the least difficult and most practical (p = 0.0001, 0.0427, respectively). One-way ANOVA revealed significance in angle differences from the set position for technique A in lateral tilt and techniques A and B in AP tilt (p = 0.0466, 0.0194, 0.0424, respectively). A comparison of positivity (overtilt) and negativity (undertilt) between the three techniques in lateral and AP tilts using Chi-square test resulted in significant differences in both directions of tilt (p < 0.0001). Technique C resulted in remounting the casts at the control position in 15.64% in both directions; this was a higher percentage than the other two techniques (A and B). Wilcoxon Matched-pairs test was used to compare between the techniques relative to angle differences from the standard position. No differences were found between technique A and B in lateral tilt position (p = 0.9271), while significance was detected in AP tilt (p < 0.0001). Significant differences were detected between technique C in comparison to A (p < 0.0001, p = 0.0303) and B (p < 0.0001) in lateral and AP tilt directions. CONCLUSIONS: Within the limitations of this study, it can be concluded that technique C (cemented post technique) was more favored among the respondents across all educational levels. This technique presented high potential in accurately reorienting casts on the dental surveyor in comparison to the tripod points and scoring techniques (p < 0.0001).

Diversity in protein profiling, pasting, empirical and dynamic dough rheological properties of meal from different durum wheat accessions.

The particle size distribution, protein profile, pasting and dough rheological properties of meal from forty-two Indian durum wheat accessions were evaluated. Meal from accessions with higher grain hardness index (GHI) showed a high proportion of large size particles with higher protein content and lower paste viscosities. Elastic and viscous modulii (G' and G″) of dough were negatively correlated with paste viscosities, which was associated with the presence/absence of LMW-GS and HMW-GS. Wheat accessions with allelic combinations of (13 + 16) with 97 + 91 kDa polypeptides (PPs) had higher G' and G″. The accession with 35 kDa PP showed higher while those with 35 and 62 kDa PPs showed lower paste viscosity. Among all accessions, 25 accessions possess 7 + 8 (97 and 88 kDa) type HMW-GS allelic combination. Durum accessions with diverse GHI, particle size distribution, protein profile, paste and dough rheology indicates their variation in milling and processing behaviour.

Simultaneous Emergence of Multidrug-Resistant Candida auris on 3 Continents Confirmed by Whole-Genome Sequencing and Epidemiological Analyses.

BACKGROUND: Candida auris, a multidrug-resistant yeast that causes invasive infections, was first described in 2009 in Japan and has since been reported from several countries. METHODS: To understand the global emergence and epidemiology of C. auris, we obtained isolates from 54 patients with C. auris infection from Pakistan, India, South Africa, and Venezuela during 2012-2015 and the type specimen from Japan. Patient information was available for 41 of the isolates. We conducted antifungal susceptibility testing and whole-genome sequencing (WGS). RESULTS: Available clinical information revealed that 41% of patients had diabetes mellitus, 51% had undergone recent surgery, 73% had a central venous catheter, and 41% were receiving systemic antifungal therapy when C. auris was isolated. The median time from admission to infection was 19 days (interquartile range, 9-36 days), 61% of patients had bloodstream infection, and 59% died. Using stringent break points, 93% of isolates were resistant to fluconazole, 35% to amphotericin B, and 7% to echinocandins; 41% were resistant to 2 antifungal classes and 4% were resistant to 3 classes. WGS demonstrated that isolates were grouped into unique clades by geographic region. Clades were separated by thousands of single-nucleotide polymorphisms, but within each clade isolates were clonal. Different mutations in ERG11 were associated with azole resistance in each geographic clade. CONCLUSIONS: C. auris is an emerging healthcare-associated pathogen associated with high mortality. Treatment options are limited, due to antifungal resistance. WGS analysis suggests nearly simultaneous, and recent, independent emergence of different clonal populations on 3 continents. Risk factors and transmission mechanisms need to be elucidated to guide control measures.

Building Global Epidemiology and Response Capacity with Field Epidemiology Training Programs.

More than ever, competent field epidemiologists are needed worldwide. As known, new, and resurgent communicable diseases increase their global impact, the International Health Regulations and the Global Health Security Agenda call for sufficient field epidemiologic capacity in every country to rapidly detect, respond to, and contain public health emergencies, thereby ensuring global health security. To build this capacity, for >35 years the US Centers for Disease Control and Prevention has worked with countries around the globe to develop Field Epidemiology Training Programs (FETPs). FETP trainees conduct surveillance activities and outbreak investigations in service to ministry of health programs to prevent and control infectious diseases of global health importance such as polio, cholera, tuberculosis, HIV/AIDS, malaria, and emerging zoonotic infectious diseases. FETP graduates often rise to positions of leadership to direct such programs. By training competent epidemiologists to manage public health events locally and support public health systems nationally, health security is enhanced globally.

Identification of potential molecular associations between chikungunya virus non-structural protein 2 and human host proteins.

Chikungunya virus (CHIKV) non-structural protein 2 (nsP2) is considered to be the master regulator of viral RNA replication and host responses generated during viral infection. This protein has two main functional domains: an N-terminal domain which exhibits NTPase, RNA triphosphatase and helicase activities and a C-terminal protease domain. Understanding how CHIKV nsP2 interacts with its host proteins is essential for elucidating all the required processes for viral replication and pathogenesis along with the identification of potential targets for antiviral therapy. In current study yeast two-hybrid (Y2H) screening of a human fetal brain cDNA library was performed using nsP2 protein as bait. The analysis identified seven host proteins (CCDC130, CPNE6, POLR2C, MAPK9, EIF4A2, EEF1A1 and EIF3I) as putative interactors of CHIKV nsP2 which were selected for further analysis based on their roles in host cellular machinery. The gene ontology analysis indicates that these proteins are mainly involved in apoptosis, transcription and translational mechanism of host cell. Domain mapping of nsP2 revealed that these associations are not random connections but instead they have functional significance. Further studies to identify the amino acid residues and their chemical interactions that may help in opening new possibilities for preventing these interactions, thus reducing chances of chikungunya infection were performed. This study expands the understanding of CHIKV-host interactions and is important for rational approaches of discovering new antiviral agents.

Effect of a brief smoking cessation intervention on adult tobacco smokers with pulmonary tuberculosis: A cluster randomized controlled trial from North India.

BACKGROUND: An association between smoking and poor tuberculosis (TB) treatment outcomes has been globally established. Various smoking cessation interventions (SCIs) have been proven worldwide to curb smoking behavior. There is a need for evidence to assess if SCI increases the chance of successful treatment outcome among TB patients. OBJECTIVES: To assess the effectiveness of a brief SCI; The Ask, Brief, Cessation support (ABC) package, on treatment outcomes and smoking cessation in smear-positive adult pulmonary TB patients. METHODS: A cluster, randomized controlled trial was conducted wherein 17 designated microscopic centers of Chandigarh, India were randomly assigned using a computer-generated randomization sequence to receive SCI within directly observed treatment, short (DOTS) services, or existing standard of care. Eligible and consenting smokers (15 + years) registered as smear-positive pulmonary TB for DOTS (n = 156) between January and June 2013 were enrolled. Smoking cessation (self-reported) was assessed at intervals till the end of treatment. End TB treatment outcomes were extracted from patient records. RESULTS: Treatment success was lower in intervention arm (83.6%) as compared control arm (88.2%), but the difference was statistically insignificant (P = 0.427). Smoking cessation was higher in intervention arm (80.2%) compared to comparison arm (57.5%) (adjusted incidence risk ratio = 1.56; 95% confidence interval = 1.24-1.93; P < 0.0001). CONCLUSIONS: SCI is effective in inducing smoking cessation among TB patients. No association of SCI with TB treatment outcomes could be detected.

Opening gambit: Strategic options to initiate the tobacco endgame.

Endgame strategies to rapidly hasten the decline of tobacco are already well within reach; a few plausible policy options are outlined herein for policy practitioners, tobacco control advocates, and public health specialists. The implementation of these measures which already exist within the gamut of existing legislation requires the galvanization of political will. The options we essay include liquidating existing public investments in tobacco, holding tobacco companies accountable within the jurisdictions of their operations, fixing liability for injury and the imposition of realistic costs on insurance providers.

Global, regional, and national disability-adjusted life years (DALYs) for 306 diseases and injuries and healthy life expectancy (HALE) for 188 countries, 1990-2013: quantifying the epidemiological transition.

BACKGROUND: The Global Burden of Disease Study 2013 (GBD 2013) aims to bring together all available epidemiological data using a coherent measurement framework, standardised estimation methods, and transparent data sources to enable comparisons of health loss over time and across causes, age-sex groups, and countries. The GBD can be used to generate summary measures such as disability-adjusted life-years (DALYs) and healthy life expectancy (HALE) that make possible comparative assessments of broad epidemiological patterns across countries and time. These summary measures can also be used to quantify the component of variation in epidemiology that is related to sociodemographic development. METHODS: We used the published GBD 2013 data for age-specific mortality, years of life lost due to premature mortality (YLLs), and years lived with disability (YLDs) to calculate DALYs and HALE for 1990, 1995, 2000, 2005, 2010, and 2013 for 188 countries. We calculated HALE using the Sullivan method; 95% uncertainty intervals (UIs) represent uncertainty in age-specific death rates and YLDs per person for each country, age, sex, and year. We estimated DALYs for 306 causes for each country as the sum of YLLs and YLDs; 95% UIs represent uncertainty in YLL and YLD rates. We quantified patterns of the epidemiological transition with a composite indicator of sociodemographic status, which we constructed from income per person, average years of schooling after age 15 years, and the total fertility rate and mean age of the population. We applied hierarchical regression to DALY rates by cause across countries to decompose variance related to the sociodemographic status variable, country, and time. FINDINGS: Worldwide, from 1990 to 2013, life expectancy at birth rose by 6·2 years (95% UI 5·6-6·6), from 65·3 years (65·0-65·6) in 1990 to 71·5 years (71·0-71·9) in 2013, HALE at birth rose by 5·4 years (4·9-5·8), from 56·9 years (54·5-59·1) to 62·3 years (59·7-64·8), total DALYs fell by 3·6% (0·3-7·4), and age-standardised DALY rates per 100 000 people fell by 26·7% (24·6-29·1). For communicable, maternal, neonatal, and nutritional disorders, global DALY numbers, crude rates, and age-standardised rates have all declined between 1990 and 2013, whereas for non-communicable diseases, global DALYs have been increasing, DALY rates have remained nearly constant, and age-standardised DALY rates declined during the same period. From 2005 to 2013, the number of DALYs increased for most specific non-communicable diseases, including cardiovascular diseases and neoplasms, in addition to dengue, food-borne trematodes, and leishmaniasis; DALYs decreased for nearly all other causes. By 2013, the five leading causes of DALYs were ischaemic heart disease, lower respiratory infections, cerebrovascular disease, low back and neck pain, and road injuries. Sociodemographic status explained more than 50% of the variance between countries and over time for diarrhoea, lower respiratory infections, and other common infectious diseases; maternal disorders; neonatal disorders; nutritional deficiencies; other communicable, maternal, neonatal, and nutritional diseases; musculoskeletal disorders; and other non-communicable diseases. However, sociodemographic status explained less than 10% of the variance in DALY rates for cardiovascular diseases; chronic respiratory diseases; cirrhosis; diabetes, urogenital, blood, and endocrine diseases; unintentional injuries; and self-harm and interpersonal violence. Predictably, increased sociodemographic status was associated with a shift in burden from YLLs to YLDs, driven by declines in YLLs and increases in YLDs from musculoskeletal disorders, neurological disorders, and mental and substance use disorders. In most country-specific estimates, the increase in life expectancy was greater than that in HALE. Leading causes of DALYs are highly variable across countries. INTERPRETATION: Global health is improving. Population growth and ageing have driven up numbers of DALYs, but crude rates have remained relatively constant, showing that progress in health does not mean fewer demands on health systems. The notion of an epidemiological transition--in which increasing sociodemographic status brings structured change in disease burden--is useful, but there is tremendous variation in burden of disease that is not associated with sociodemographic status. This further underscores the need for country-specific assessments of DALYs and HALE to appropriately inform health policy decisions and attendant actions. FUNDING: Bill & Melinda Gates Foundation.

Low-Cost Air Quality Monitoring Methods to Assess Compliance With Smoke-Free Regulations: A Multi-Center Study in Six Low- and Middle-Income Countries.

INTRODUCTION: Many low- and middle-income countries (LMICs) have enacted legislation banning smoking in public places, yet enforcement remains challenging. The aim of this study was to assess the feasibility of using a validated low-cost methodology (the Dylos DC1700) to provide objective evidence of smoke-free (SF) law compliance in hospitality venues in urban LMIC settings, where outdoor air pollution levels are generally high. METHODS: Teams measured indoor fine particulate matter (PM2.5) concentrations and systematically observed smoking behavior and SF signage in a convenience sample of hospitality venues (bars, restaurants, cafes, and hotels) covered by existing SF legislation in Mexico, Pakistan, Indonesia, Chad, Bangladesh, and India. Outdoor air PM2.5 was also measured on each sampling day. RESULTS: Data were collected from 626 venues. Smoking was observed during almost one-third of visits with substantial differences between countries-from 5% in India to 72% in Chad. After excluding venues where other combustion sources were observed, secondhand smoke (SHS) derived PM2.5 was calculated by subtracting outdoor ambient PM2.5 concentrations from indoor measurements and was, on average, 34 µg/m(3) in venues with observed smoking-compared to an average value of 0 µg/m(3) in venues where smoking was not observed (P < .001). In over one-quarter of venues where smoking was observed the difference between indoor and outdoor PM2.5 concentrations exceeded 64 µg/m(3). CONCLUSIONS: This study suggests that low-cost air quality monitoring is a viable method for improving knowledge about environmental SHS and can provide indicative data on compliance with local and national SF legislation in hospitality venues in LMICs. IMPLICATIONS: Air quality monitoring can provide objective scientific data on SHS and air quality levels in venues to assess the effectiveness of SF laws and identify required improvements. Equipment costs and high outdoor air pollution levels have hitherto limited application in LMICs. This study tested the feasibility of using a validated low-cost methodology in hospitality venues in six LMIC urban settings and suggests this is a viable method for improving knowledge about SHS exposure and can provide indicative data on compliance with SF legislation.

GCN2 is required to increase fibroblast growth factor 21 and maintain hepatic triglyceride homeostasis during asparaginase treatment.

The antileukemic agent asparaginase triggers the amino acid response (AAR) in the liver by activating the eukaryotic initiation factor 2 (eIF2) kinase general control nonderepressible 2 (GCN2). To explore the mechanism by which AAR induction is necessary to mitigate hepatic lipid accumulation and prevent liver dysfunction during continued asparaginase treatment, wild-type and Gcn2 null mice were injected once daily with asparaginase or phosphate buffered saline for up to 14 days. Asparaginase induced mRNA expression of multiple AAR genes and greatly increased circulating concentrations of the metabolic hormone fibroblast growth factor 21 (FGF21) independent of food intake. Loss of Gcn2 precluded mRNA expression and circulating levels of FGF21 and blocked mRNA expression of multiple genes regulating lipid synthesis and metabolism including Fas, Ppara, Pparg, Acadm, and Scd1 in both liver and white adipose tissue. Furthermore, rates of triglyceride export and protein expression of apolipoproteinB-100 were significantly reduced in the livers of Gcn2 null mice treated with asparaginase, providing a mechanistic basis for the increase in hepatic lipid content. Loss of AAR-regulated antioxidant defenses in Gcn2 null livers was signified by reduced Gpx1 gene expression alongside increased lipid peroxidation. Substantial reductions in antithrombin III hepatic expression and activity in the blood of asparaginase-treated Gcn2 null mice indicated liver dysfunction. These results suggest that the ability of the liver to adapt to prolonged asparaginase treatment is influenced by GCN2-directed regulation of FGF21 and oxidative defenses, which, when lost, corresponds with maladaptive effects on lipid metabolism and hemostasis.

Global, regional, and national levels and causes of maternal mortality during 1990-2013: a systematic analysis for the Global Burden of Disease Study 2013.

BACKGROUND: The fifth Millennium Development Goal (MDG 5) established the goal of a 75% reduction in the maternal mortality ratio (MMR; number of maternal deaths per 100,000 livebirths) between 1990 and 2015. We aimed to measure levels and track trends in maternal mortality, the key causes contributing to maternal death, and timing of maternal death with respect to delivery. METHODS: We used robust statistical methods including the Cause of Death Ensemble model (CODEm) to analyse a database of data for 7065 site-years and estimate the number of maternal deaths from all causes in 188 countries between 1990 and 2013. We estimated the number of pregnancy-related deaths caused by HIV on the basis of a systematic review of the relative risk of dying during pregnancy for HIV-positive women compared with HIV-negative women. We also estimated the fraction of these deaths aggravated by pregnancy on the basis of a systematic review. To estimate the numbers of maternal deaths due to nine different causes, we identified 61 sources from a systematic review and 943 site-years of vital registration data. We also did a systematic review of reports about the timing of maternal death, identifying 142 sources to use in our analysis. We developed estimates for each country for 1990-2013 using Bayesian meta-regression. We estimated 95% uncertainty intervals (UIs) for all values. FINDINGS: 292,982 (95% UI 261,017-327,792) maternal deaths occurred in 2013, compared with 376,034 (343,483-407,574) in 1990. The global annual rate of change in the MMR was -0·3% (-1·1 to 0·6) from 1990 to 2003, and -2·7% (-3·9 to -1·5) from 2003 to 2013, with evidence of continued acceleration. MMRs reduced consistently in south, east, and southeast Asia between 1990 and 2013, but maternal deaths increased in much of sub-Saharan Africa during the 1990s. 2070 (1290-2866) maternal deaths were related to HIV in 2013, 0·4% (0·2-0·6) of the global total. MMR was highest in the oldest age groups in both 1990 and 2013. In 2013, most deaths occurred intrapartum or postpartum. Causes varied by region and between 1990 and 2013. We recorded substantial variation in the MMR by country in 2013, from 956·8 (685·1-1262·8) in South Sudan to 2·4 (1·6-3·6) in Iceland. INTERPRETATION: Global rates of change suggest that only 16 countries will achieve the MDG 5 target by 2015. Accelerated reductions since the Millennium Declaration in 2000 coincide with increased development assistance for maternal, newborn, and child health. Setting of targets and associated interventions for after 2015 will need careful consideration of regions that are making slow progress, such as west and central Africa. FUNDING: Bill & Melinda Gates Foundation.

Effective smoke-free policies in achieving a high level of compliance with smoke-free law: experiences from a district of North India.

BACKGROUND: Compliance survey of smoke-free law is an effective means of measuring progress towards a smoke-free society. They also help policy makers to take action where strengthening measures are required. India has a comprehensive tobacco control law known as Cigarettes and Other Tobacco Products Act (COTPA 2003) which prohibits smoking in public places and requires display of 'No smoking' signages with proper specifications at conspicuous points. However, its implementation and enforcement are still a matter of concern. AIMS AND OBJECTIVES: To ascertain the level of compliance with smoke-free law in public places of a district of North India. METHODOLOGY: A cross sectional study was conducted in the months of November-December 2011 in district SAS Nagar Mohali of North India. The public places including hotels/restaurants/bars/shopping malls, government offices, educational institutions, healthcare facilities and transit stations were surveyed. The study tool was adapted from the guide on 'Assessing compliance with smoke-free law' developed jointly by the Campaign for Tobacco Free Kids, Johns Hopkins Bloomberg School of Public Health and International Union against Tuberculosis and Lung Disease. RESULTS: The overall compliance rate towards section 4 of COTPA was 92.3%. No active smoking was observed in 94.2% of the public places. In 90% of the public places 'No Smoking' signage were displayed as per COTPA. Health and educational institutions had maximum compliance with the smoke-free law while transit sites showed the least compliance. CONCLUSIONS: Compliance to the smoke-free law was high in the study.

Floristic diversity and distribution pattern of plant communities along altitudinal gradient in Sangla Valley, Northwest Himalaya.

Himalayas are globally important biodiversity hotspots and are facing rapid loss in floristic diversity and changing pattern of vegetation due to various biotic and abiotic factors. This has necessitated the qualitative and quantitative assessment of vegetation here. The present study was conducted in Sangla Valley of northwest Himalaya aiming to assess the structure of vegetation and its trend in the valley along the altitudinal gradient. In the forest and alpine zones of the valley, 15 communities were recorded. Study revealed 320 species belonging to 199 genera and 75 families. Asteraceae, Rosaceae, Apiaceae, and Ranunculaceae were dominant. Among genera, Artemisia followed by Polygonum, Saussurea, Berberis, and Thalictrum were dominant. Tree and shrub's density ranged from 205 to 600 and from 105 to 1030 individual per hectare, respectively, whereas herbs ranged from 22.08 to 78.95 individual/m(2). Nearly 182 species were native to the Himalaya. Maximum altitudinal distribution of few selected climate sensitive species was found to be highest in northeast and north aspects. This study gives an insight into the floristic diversity and community structure of the fragile Sangla Valley which was hitherto not available.

Complementary and Alternative Medicine/Therapy for Tobacco Cessation in India: A Secondary Analysis of GATS-1 and 2.

Background: India has nearly 267 million adult tobacco users, with a slowly improving quitting rate. Among the many approaches to quitting the habit, such as counseling, nicotine replacement therapy, nicotine patch or gum, and prescribed allopathic medicines. Complementary and alternative medicine/therapy (CAM), a thousand-year-old practice in India, may also prove to be a potential method in tobacco cessation; however, there is scarce literature on the extent of use of CAM among tobacco users who attempt to quit the habit. Therefore, this study attempts to examine the potential of CAM as a strategy for tobacco control in India. Material and Methods: We undertook a secondary analysis of the data from both rounds of the Global Adult Tobacco Survey (GATS 2009 and 2016). The dependent variable included in the analysis was the use of traditional medicine as a method for quitting tobacco in three types of users-smokers, smokeless tobacco users, and dual users. The prevalence of CAM use was reported, and Chi-square test was applied to find the factors significantly associated with the use of CAM among tobacco users considering a P value of 0.05 to be statistically significant. Results: The overall prevalence of traditional medicine use for GATS-1 was observed to be more among dual users (4%), while for GATS-2, it was highest among smokers (3%). For both rounds of the GATS survey, the use of traditional medicine was found to be higher among males, rural residents, users with no education or less than primary education, and the eastern region. Conclusions: CAM has a promising potential for supporting tobacco cessation provided a concerted effort is undertaken to standardize pharmacopeia and establish robust clinical evidence. In addition, there is a need to create awareness, build the capacity of healthcare providers, and foster academic-industrial research in indigenous Ayurveda, Yoga, Naturopathy, Unani, Siddha, and Homeopathy (AYUSH) systems.

Molecular diversity in rice blast resistance gene Pi-ta makes it highly effective against dynamic population of Magnaporthe oryzae.

Rice blast is one of the important diseases of rice which can be effectively managed by the deployment of resistance genes. Pi-ta is one of the major blast resistant genes effective against pathogen populations in different parts of India. We analysed allelic variants of Pi-ta from 48 rice lines selected after phenotyping of 529 rice landraces across three eco-geographical blast hot spot regions. Besides, Pi-ta orthologue sequences of 220 rice accessions belonging to wild and cultivated species of rice were also included in the study for a better evo-devo perspective of the diversity present in the gene and the selection pressures acting on this locus. We obtained high nucleotide variations (SNPs and insertion-deletions) in the intronic region. We also identified 64 haplotypes based on nucleotide polymorphism in these alleles. Pi-ta orthologues of Indian landraces were scattered in eight major haplotypes indicating its heterogenous nature. We identified a total of 47 different Pi-ta protein variants on the basis of deduced amino acid residues amongst the orthologues. Five unique and novel Pi-ta variants were identified for the first time in rice landraces exhibiting different reaction types against the Magnaporthe oryzae population. A high value of Pi(non/syn) was observed only in the leucine-rich domain of the alleles cloned from Indian landraces, indicating strong selective forces acting on this region. The detailed molecular analysis of the Pi-ta orthologues provides insights to a high degree of inter- and intraspecific relationships amongst the Oryza species. We identified rice landraces possessing the effective alleles of this resistance gene which can be used in future blast resistance breeding programmes.