Burden of Typhoid and Paratyphoid Fever in India.

BACKGROUND: In 2017, more than half the cases of typhoid fever worldwide were projected to have occurred in India. In the absence of contemporary population-based data, it is unclear whether declining trends of hospitalization for typhoid in India reflect increased antibiotic treatment or a true reduction in infection. METHODS: From 2017 through 2020, we conducted weekly surveillance for acute febrile illness and measured the incidence of typhoid fever (as confirmed on blood culture) in a prospective cohort of children between the ages of 6 months and 14 years at three urban sites and one rural site in India. At an additional urban site and five rural sites, we combined blood-culture testing of hospitalized patients who had a fever with survey data regarding health care use to estimate incidence in the community. RESULTS: A total of 24,062 children who were enrolled in four cohorts contributed 46,959 child-years of observation. Among these children, 299 culture-confirmed typhoid cases were recorded, with an incidence per 100,000 child-years of 576 to 1173 cases in urban sites and 35 in rural Pune. The estimated incidence of typhoid fever from hospital surveillance ranged from 12 to 1622 cases per 100,000 child-years among children between the ages of 6 months and 14 years and from 108 to 970 cases per 100,000 person-years among those who were 15 years of age or older. Salmonella enterica serovar Paratyphi was isolated from 33 children, for an overall incidence of 68 cases per 100,000 child-years after adjustment for age. CONCLUSIONS: The incidence of typhoid fever in urban India remains high, with generally lower estimates of incidence in most rural areas. (Funded by the Bill and Melinda Gates Foundation; NSSEFI Clinical Trials Registry of India number, CTRI/2017/09/009719; ISRCTN registry number, ISRCTN72938224.).

Genomic analysis unveils genome degradation events and gene flux in the emergence and persistence of S. Paratyphi A lineages.

Paratyphoid fever caused by S. Paratyphi A is endemic in parts of South Asia and Southeast Asia. The proportion of enteric fever cases caused by S. Paratyphi A has substantially increased, yet only limited data is available on the population structure and genetic diversity of this serovar. We examined the phylogenetic distribution and evolutionary trajectory of S. Paratyphi A isolates collected as part of the Indian enteric fever surveillance study "Surveillance of Enteric Fever in India (SEFI)." In the study period (2017-2020), S. Paratyphi A comprised 17.6% (441/2503) of total enteric fever cases in India, with the isolates highly susceptible to all the major antibiotics used for treatment except fluoroquinolones. Phylogenetic analysis clustered the global S. Paratyphi A collection into seven lineages (A-G), and the present study isolates were distributed in lineages A, C and F. Our analysis highlights that the genome degradation events and gene acquisitions or losses are key molecular events in the evolution of new S. Paratyphi A lineages/sub-lineages. A total of 10 hypothetically disrupted coding sequences (HDCS) or pseudogenes-forming mutations possibly associated with the emergence of lineages were identified. The pan-genome analysis identified the insertion of P2/PSP3 phage and acquisition of IncX1 plasmid during the selection in 2.3.2/2.3.3 and 1.2.2 genotypes, respectively. We have identified six characteristic missense mutations associated with lipopolysaccharide (LPS) biosynthesis genes of S. Paratyphi A, however, these mutations confer only a low structural impact and possibly have minimal impact on vaccine effectiveness. Since S. Paratyphi A is human-restricted, high levels of genetic drift are not expected unless these bacteria transmit to naive hosts. However, public-health investigation and monitoring by means of genomic surveillance would be constantly needed to avoid S. Paratyphi A serovar becoming a public health threat similar to the S. Typhi of today.

Ononin: A comprehensive review of anticancer potential of natural isoflavone glycoside.

Cancer is one of the major causes of death worldwide, with more than 10 million deaths annually. Despite tremendous advances in the health sciences, cancer continues to be a substantial global contributor to mortality. The current treatment methods demand a paradigm shift that not only improves therapeutic efficacy but also minimizes the side effects of conventional medications. Recently, an increased interest in the potential of natural bioactive compounds in the treatment of several types of cancer has been observed. Ononin, also referred to as formononetin-7-O-ß-d-glucoside, is a natural isoflavone glycoside, derived from the roots, stems, and rhizomes of various plants. It exhibits a variety of pharmacological effects, including Antiangiogenic, anti-inflammatory, antiproliferative, proapoptotic, and antimetastatic activities. The current review presents a thorough overview of sources, chemistry, pharmacokinetics, and the role of ononin in affecting various mechanisms involved in cancer. The review also discusses potential synergistic interactions with other compounds and therapies. The combined synergistic effect of ononin with other compounds increased the efficacy of treatment methods. Finally, the safety studies, comprising both in vitro and in vivo assessments of ononin's anticancer activities, are described.

Intussusception after Rotavirus Vaccine Introduction in India.

BACKGROUND: A three-dose, oral rotavirus vaccine (Rotavac) was introduced in the universal immunization program in India in 2016. A prelicensure trial involving 6799 infants was not large enough to detect a small increased risk of intussusception. Postmarketing surveillance data would be useful in assessing whether the risk of intussusception would be similar to the risk seen with different rotavirus vaccines used in other countries. METHODS: We conducted a multicenter, hospital-based, active surveillance study at 27 hospitals in India. Infants meeting the Brighton level 1 criteria of radiologic or surgical confirmation of intussusception were enrolled, and rotavirus vaccination was ascertained by means of vaccination records. The relative incidence (incidence during the risk window vs. all other times) of intussusception among infants 28 to 365 days of age within risk windows of 1 to 7 days, 8 to 21 days, and 1 to 21 days after vaccination was evaluated by means of a self-controlled case-series analysis. For a subgroup of patients, a matched case-control analysis was performed, with matching for age, sex, and location. RESULTS: From April 2016 through June 2019, a total of 970 infants with intussusception were enrolled, and 589 infants who were 28 to 365 days of age were included in the self-controlled case-series analysis. The relative incidence of intussusception after the first dose was 0.83 (95% confidence interval [CI], 0.00 to 3.00) in the 1-to-7-day risk window and 0.35 (95% CI, 0.00 to 1.09) in the 8-to-21-day risk window. Similar results were observed after the second dose (relative incidence, 0.86 [95% CI, 0.20 to 2.15] and 1.23 [95% CI, 0.60 to 2.10] in the respective risk windows) and after the third dose (relative incidence, 1.65 [95% CI, 0.82 to 2.64] and 1.08 [95% CI, 0.69 to 1.73], respectively). No increase in intussusception risk was found in the case-control analysis. CONCLUSIONS: The rotavirus vaccine produced in India that we evaluated was not associated with intussusception in Indian infants. (Funded by the Bill and Melinda Gates Foundation and others.).

Recent advances in BCRP-induced breast cancer resistance treatment with marine-based natural products.

Breast cancer is the prominent cause of cancer-related death in women globally in terms of incidence and mortality. Despite, recent advances in the management of breast cancer, there are still a lot of cases of resistance to medicines, which is currently one of the biggest problems faced by researchers across the globe. Out of several mechanisms, breast cancer resistance protein (BCRP) arbitrated drug resistance is a major concern. Hormonal, cytotoxic and immunotherapeutic drugs are used in the systemic therapy of breast cancer. It is vital to choose drugs based on the clinical and molecular attributes of the tumor to provide better treatment with greater efficacy and minimal harm. Given the aforementioned necessity, the use of marine flora in treating breast cancer cannot be neglected. The scientists also stressed the value of marine-derived goods in avoiding breast cancer resistance. Future research into the identification of anticancer drugs will heavily draw upon the marine environment's ample supply of marine-derived natural products (MNPs), which have a wide range of biological functions. Cell cycle arrest, induction of apoptosis and anti-angiogenic, anti-proliferative and anti-metastasis actions are all part of their processes. The overview of breast cancer, the mechanisms underlying its resistance, recent clinical trials based on marine-derived products in breast cancer and the use of marine products in the treatment of breast cancer are highlighted in this paper. Moreover, the authors also emphasised the importance of marine-derived products in preventing breast cancer resistance.

Acinetobacter baumannii in suspected bacterial infections: Association between multidrug resistance, virulence genes, & biofilm production.

BACKGROUND OBJECTIVES: Acinetobacter baumannii has emerged as a nosocomial pathogen with a tendency of high antibiotic resistance and biofilm production. This study aimed to determine the occurrence of A. baumannii from different clinical specimens of suspected bacterial infections and furthermore to see the association of biofilm production with multidrug resistance and expression of virulence factor genes in A. baumannii. METHODS: A. baumannii was confirmed in clinical specimens by the detection of the blaOXA-51-like gene. Biofilm production was tested by microtitre plate assay and virulence genes were detected by real-time PCR. RESULTS: A. baumannii was isolated from a total of 307 clinical specimens. The isolate which showed the highest number of A. baumannii was an endotracheal tube specimen (44.95%), then sputum (19.54%), followed by pus (17.26%), urine (7.49%) and blood (5.86%), and <2 per cent from body fluids, catheter-tips and urogenital specimens. A resistance rate of 70-81.43 per cent against all antibiotics tested, except colistin and tigecycline, was noted, and 242 (78.82%) isolates were multidrug-resistant (MDR). Biofilm was detected in 205 (66.78%) with a distribution of 54.1 per cent weak, 10.42 per cent medium and 2.28 per cent strong biofilms. 71.07 per cent of MDR isolates produce biofilm (P<0.05). Amongst virulence factor genes, 281 (91.53%) outer membrane protein A (OmpA) and 98 (31.92%) biofilm-associated protein (Bap) were detected. Amongst 100 carbapenem-resistant A. baumannii, the blaOXA-23-like gene was predominant (96%), the blaOXA-58-like gene (6%) and none harboured the blaOXA-24-like gene. The metallo-ß-lactamase genes blaIMP-1 (4%) and blaVIM-1(8%) were detected, and 76 per cent showed the insertion sequence ISAba1. INTERPRETATION CONCLUSIONS: The majority of isolates studied were from lower respiratory tract specimens. The high MDR rate and its positive association with biofilm formation indicate the nosocomial distribution of A. baumannii. The biofilm formation and the presence of Bap were not interrelated, indicating that biofilm formation was not regulated by a single factor. The MDR rate and the presence of OmpA and Bap showed a positive association (P<0.05). The isolates co-harbouring different carbapenem resistance genes were the predominant biofilm producers, which will seriously limit the therapeutic options suggesting the need for strict antimicrobial stewardship and molecular surveillance in hospitals.

Effect of health promotion interventions on small portion size consumption behavior among college students.

Background: Large food portion size is contributing toward overweight and obesity rates and has been found directly proportional to increase in portion size. Objectives: The study was done to see the effect of health promotion intervention on small portion size consumption behavior using multitheory model (MTM). Materials and Methods: A quasi-experimental study was conducted among students of age groups 18 - 21 years in two different colleges from North India between 2019 to 2020. About 150 participants in the intervention group as well as control group were selected and health promotion intervention in the form of motivational group counseling, one-to-one counseling, Power Point presentations, lectures, and messages were given to participants in intervention group. Difference in difference of proportions for meal consumption behavior and the difference in the difference of means for body mass index, waist-hip ratio and for constructs of MTM for portion size consumption behavior were calculated. Paired t-test was used to test the significance between the continuous variables. Results: There was a significant reduction (46% vs. 11%, P < 0.001) in proportion of participants consuming large portion-sized meals in the intervention group as compared to the control group. The mean change in constructs (participatory dialogues,behavioral confidence, change in physical environment, emotional transformation and practice for change) for portion size consumption behavior of participants in the intervention and control groups at base line and end line was found statistically significant. Conclusion: MTM is a useful tool for health promotion and health education to predict the initiation and sustenance of health behavior change.

Measurement and mapping of maternal health service coverage through a novel composite index: a sub-national level analysis in India.

BACKGROUND: Expansion of maternal health service coverage is crucial for the survival and wellbeing of both mother and child. To date, limited literature exists on the measurement of maternal health service coverage at the sub-national level in India. The prime objectives of the study were to comprehensively measure the maternal health service coverage by generating a composite index, map India by categorizing it into low, medium and high zones and examine its incremental changes over time. METHODS: Utilising a nationally representative time series data of 15 key indicators spread across three domains of antenatal care, intranatal care and postnatal care, we constructed a novel 'Maternal Health Service Coverage Index' (MHSI) for 29 states and 5 union territories of India for the base (2017-18) and reference (2019-20) years. Following a rigorous procedure, MHSI scores were generated using both arithmetic mean and geometric mean approaches. We categorized India into low, medium and high maternal health service coverage zones and further generated geospatial maps to examine the extent and transition of maternal health service coverage from base to reference year. RESULTS: India registered the highest mean percentage coverage (93.7%) for 'institutional delivery' and the lowest for 'treatment for obstetric complications' (9.3%) among all the indicators. Depending on the usage of arithmetic mean and geometric mean approaches, the maternal health service coverage index score for India exhibited marginal incremental change (between 0.015-0.019 index points) in the reference year. West zone exhibited an upward transition in the coverage of maternal health service indicators, while none of the zones recorded a downward movement. The states of Mizoram (east zone) and the Union Territory of Puducherry (south zone) showed a downward transition. Union territories of Dadra & Nagar Haveli (west zone) and Chandigarh (north zone), along with the states of Maharashtra (west zone), Assam, as well as Jharkhand (both from the east & north east zone), showed upward transition. CONCLUSION: Overall, maternal health service coverage is increasing across India. Our study offers a novel summary measure to comprehensively quantify the coverage of maternal health services, which can momentously help India identify lagged indicators and low performing regions, thereby warranting the targeted interventions and concentrated programmatic efforts to bolster the maternal health service coverage at the sub-national level.

Reporting adverse events of ChAdOx1 nCoV-19 coronavirus vaccine (Recombinant) among the vaccinated healthcare professionals: A cross-sectional survey.

Background & objectives: The safety of the ChAdOx1 nCoV-19 vaccine is a cause of concern for many who have been vaccinated. The people have multiple concerns and fear regarding the adverse events of the vaccine. Thus, this study was undertaken to establish the safety profile of ChAdOx1 nCoV-19 Corona Virus Vaccine (Recombinant) among the healthcare professionals. Methods: This was a descriptive cross-sectional survey. After taking clearance from the institutional ethics committee 1500 healthcare professionals, who had their vaccination in the past two weeks were selected. They were provided with an online survey proforma regarding adverse events following immunization (AEFIs) of COVID-19 vaccine developed using google forms with an informed consent form affixed to it. Results: A total of 1036 individuals participated in the study. The mean and median (inter quartile range) age of the participants was 37.7 ±11.25 and 35 (29-46) yr, respectively. Of these, 52.1 per cent were female, 29.3 per cent were doctors, 33.4 per cent were nurses and 9.5 per cent were paramedical staff. Forty six per cent participants experienced one or more minor AEFIs such as pain, tenderness, redness, etc. at the injection site. Fatigue (31.75%), generalized feeling of unwell (28.57%), muscle pain (23.16%) and fever (21.71%) were the most commonly reported systemic AEFIs followed by headache (20.07%), dizziness (10.03%) and joint pains (15.25%). Most of them experienced these AEFIs within 24 h of the first dose of administration. About 42 per cent of the participants took oral antipyretics/analgesics for managing the AEFIs. Interpretation & conclusions: ChAdOx1 nCoV-19 Corona Virus Vaccine was found to be associated with mild local and systemic AEFIs that were more common after the first dose as compared to the second dose. There adverse events could be dealt with oral over-the-counter medications, with no requirement of hospitalization.

Communication lessons learned from the 2017 measles-rubella campaign in India: perspectives from vaccine decision-makers.

In 2017, to reduce the burden of measles and rubella, a nation-wide measles-rubella campaign was launched in India. Despite detailed planning efforts that involved many stakeholders, vaccine refusal arose in several communities during the campaign. As strategic health communication and promotion is critical in any vaccine campaign, we sought to document lessons learned from the 2017 MR campaign from a strategic health communication and promotion perspective to capture lessons learned. To inform future campaigns, we conducted in-depth interviews through a perspective that is not usually captured, that of government and civil society stakeholders that had experience in vaccine campaign implementation (n = 21). We interviewed stakeholders at the national level and within three states that had diverse experiences with the campaign. Three key themes related to strategic health communication and promotion emerged: the importance of sensitizing communities at all levels through relevant and timely information about the vaccine and the vaccine campaign, leveraging key influencers to deliver tailored messaging about the importance of vaccines and mitigating vaccine misinformation rapidly. Our study findings have important implications for health communication and promotion research related to vaccine campaigns. The field must continue to enhance vaccine campaign efforts by identifying important health communication and promotion factors, including the importance of sensitization, trusted messengers that use tailored messaging and mitigating misinformation, as vaccine campaigns are crucial in improving vaccine acceptance.

Measles and rubella are diseases that cause sickness and death. Both are preventable as there are safe and effective vaccines available. Measles and rubella are significant in India. These vaccines are generally delivered to the public through vaccine campaigns. A measles­rubella vaccine campaign was implemented in 2017. In this study, we interviewed 21 government and civil society stakeholders that are involved in vaccine campaigns in India to capture lessons learned. We were interested in understanding how vaccine campaigns could be improved through health communication and promotion efforts. Stakeholders suggested to use trusted community members to inform people about the vaccine campaign, and that it was important for trusted community leaders to dispel rumors about vaccines quickly. To increase vaccine acceptance, it is critical that health communication and promotion efforts target concerns that people may have about the vaccine as well as the vaccine campaign.

Regional Water Availability and WASH Indicators as Predictors of Malnutrition in Under-5 Children: Analysis of the National Family Health Survey, India (2015-16).

BACKGROUND: Water, sanitation and hygiene (WASH) practices determine child nutrition in resource-constrained countries and are influenced by regional water availability. We assessed any relationship between malnutrition and WASH practices among under-5 children in India's areas as per water availability. METHODS: We did a secondary data analysis of the National Family Health Survey-IV. Stunting, wasting and being underweight were the significant outcomes. Regional water availability, households' source of water, sanitation and disposal of the child stool were the major independent variables. We report the prevalence estimates, bivariate associations and adjusted odds ratio to predict the child's malnutrition per regional water availability after using appropriate sampling weight. RESULTS: Of the 186 875 children, 41%, 20% and 36% were stunted, wasted and underweight. Only 26% of children had access to improved drinking water sources, whereas 50.0% were defecating in open. Around 65% of children's stools were disposed of in unhygienic ways. Undernutrition depicted a significant association with independent variables. There were higher chances of stunting with a decrease in regional water availability, unimproved sanitation and unhygienic ways of stool disposal. Wasting was intensified by all these factors, except the safe disposal of stools. CONCLUSIONS: WASH indicators exert a protective effect on undernutrition.

Ileal Perforation and Enteric Fever: Implications for Burden of Disease Estimation.

BACKGROUND: Ileal perforation occurs in about 1% of enteric fevers as a complication, with a case fatality risk (CFR) of 20%-30% in the early 1990s that decreased to 15.4% in 2011 in South East Asia. We report nontraumatic ileal perforations and its associated CFR from a 2-year prospective enteric fever surveillance across India. METHODS: The Surveillance for Enteric Fever in India (SEFI) project established a multitiered surveillance system for enteric fever between December 2017 and March 2020. Nontraumatic ileal perforations were surveilled at 8 tertiary care and 6 secondary care hospitals and classified according to etiology. RESULTS: Of the 158 nontraumatic ileal perforation cases identified,126 were consented and enrolled. Enteric fever (34.7%), tuberculosis (19.0%), malignancy (5.8%), and perforation of Meckel diverticulum (4.9%) were the common etiology. In those with enteric fever ileal perforation, the CFR was 7.1%. CONCLUSIONS: Enteric fever remains the most common cause of nontraumatic ileal perforation in India, followed by tuberculosis. Better modalities of establishing etiology are required to classify the illness, and frame management guidelines and preventive measures. CFR data are critical for comprehensive disease burden estimation and policymaking.

Cost of Illness Due to Severe Enteric Fever in India.

BACKGROUND: Lack of robust data on economic burden due to enteric fever in India has made decision making on typhoid vaccination a challenge. Surveillance for Enteric Fever network was established to address gaps in typhoid disease and economic burden. METHODS: Patients hospitalized with blood culture-confirmed enteric fever and nontraumatic ileal perforation were identified at 14 hospitals. These sites represent urban referral hospitals (tier 3) and smaller hospitals in urban slums, remote rural, and tribal settings (tier 2). Cost of illness and productivity loss data from onset to 28 days after discharge from hospital were collected using a structured questionnaire. The direct and indirect costs of an illness episode were analyzed by type of setting. RESULTS: In total, 274 patients from tier 2 surveillance, 891 patients from tier 3 surveillance, and 110 ileal perforation patients provided the cost of illness data. The mean direct cost of severe enteric fever was US$119.1 (95% confidence interval [CI], US$85.8-152.4) in tier 2 and US$405.7 (95% CI, 366.9-444.4) in tier 3; 16.9% of patients in tier 3 experienced catastrophic expenditure. CONCLUSIONS: The cost of treating enteric fever is considerable and likely to increase with emerging antimicrobial resistance. Equitable preventive strategies are urgently needed.

Evaluation of Antimicrobial Susceptibility Profile in Salmonella Typhi and Salmonella Paratyphi A: Presenting the Current Scenario in India and Strategy for Future Management.

BACKGROUND: Systematic studies to estimate the disease burden of typhoid and paratyphoid in India are limited. Therefore, a multicenter study on the Surveillance of Enteric Fever in India was carried out to estimate the incidence, clinical presentation, and antimicrobial resistance (AMR) trend. The data presented here represent the national burden of AMR in Salmonella Typhi and Salmonella Paratyphi A. METHODS: Antimicrobial susceptibility testing was performed for S. Typhi and S. Paratyphi A (n = 2373) isolates collected prospectively during a 2-year period from November 2017 to January 2020. RESULTS: Of 2373 Salmonella isolates, 2032 (85.6%) were identified as S. Typhi and 341 (14.4%) were S. Paratyphi A. Approximately 2% of S. Typhi were multidrug-resistant (MDR), whereas all 341 (100%) of S. Paratyphi A isolates were sensitive to the first-line antimicrobials. Among 98% of ciprofloxacin nonsusceptible isolates, resistance (minimum inhibitory concentration [MIC] >0.5 µg/mL) was higher in S. Typhi (37%) compared with S. Paratyphi A (20%). Azithromycin susceptibility was 99.9% and 100% with a mean MIC of 4.98 µg/mL for S. Typhi and 7.39 µg/mL for S. Paratyphi A respectively. Ceftriaxone was the only agent that retained 100% susceptibility. Moreover, beta-lactam/beta-lactamase inhibitors showed potent in vitro activity against the study isolates. CONCLUSIONS: Data obtained from this systematic surveillance study confirms the declining trend of MDR Salmonella isolates from India. The higher prevalence of ciprofloxacin nonsusceptibility enforces to limit its use and adhere to the judicious usage of azithromycin and ceftriaxone for enteric fever management.

Change in full immunization inequalities in Indian children 12-23 months: an analysis of household survey data.

BACKGROUND: India has made substantial progress in improving child health in recent years. However, the country continues to account for a large number of vaccine preventable child deaths. We estimated wealth-related full immunization inequalities in India. We also calculated the degree to which predisposing, reinforcing, and enabling factors contribute to these inequalities. METHODS: We used data from the two rounds of a large nationally representative survey done in all states in India in 2005-06 (n = 9582) and 2015-16 (n = 49,284). Full immunization status was defined as three doses of diphtheria-tetanus-pertussis vaccine, three doses of polio vaccine, one dose of Bacillus Calmette-Guérin vaccine, and one dose of measles vaccine in children 12-23 months. We compared full immunization coverage by wealth quintiles using descriptive statistics. We calculated concentration indices for full immunization coverage at the national and state levels. Using predisposing, reinforcing, and enabling factors associated with full immunization status identified from the literature, we applied a generalized linear model (GLM) framework with a binomial distribution and an identity link to decompose the concentration index. RESULTS: National full immunization coverage increased from 43.65% in 2005-06 to 62.46% in 2015-16. Overall, full immunization coverage in both 2005-06 and 2015-16 in all states was lowest in children from poorer households and improved with increasing socioeconomic status. The national concentration index decreased from 0.36 to 0.13 between the two study periods, indicating a reduction in poor-rich inequality. Similar reductions were observed for most states, except in states where inequalities were already minimal (i.e., Tamil Nadu) and in some northeastern states (i.e., Meghalaya and Manipur). In 2005-06, the contributors to wealth-related full immunization inequality were antenatal care, maternal education, and socioeconomic status. The same factors contributed to full immunization inequality in 2015-16 in addition to difficulty reaching a health facility. CONCLUSIONS: Immunization coverage and wealth-related equality have improved nationally and in most states over the last decade in India. Targeted, context-specific interventions could help address overall wealth-related full immunization inequalities. Intensified government efforts could help in this regard, particularly in high-focus states where child mortality remains high.

Impact of National Health Mission on infant mortality in India: An interrupted time series analysis.

Government of India introduced National Rural Health Mission in 2005-now transformed into National Health Mission (NHM), to bring about architectural reforms in health sector. In this study, we evaluate the overall impact of NHM on infant mortality at national and state level. Annual data on infant mortality rate (IMR) from 1990 to 2016 were obtained from Sample Registration System bulletins. With reporting year 2009 considered as cut-off point, a two-step segmented time series regression analysis was conducted. Estimates of pre-slope, post-slope and change at the point of intervention were computed by applying auto-regressive integrated moving average (1, 0, 0) while adjusting for trend and auto correlation. We found that while IMR reduced from around 80 to 34 per 1000 live births at the national level from 1990 to 2016, the annual rate of reduction increased from 1.6 per 1000 live births before NHM to 2.2 per 1000 live births after NHM. This is estimated to have averted 248,212 infant deaths in India, between 2005 and 2017. The rate of decline in IMR accelerated in 13 out of 17 larger states, most significantly in Andhra Pradesh, Gujarat, Assam, Haryana, Punjab and Uttar Pradesh. NHM has thus been successful in accelerating the overall rate of reduction in IMR in India. There is still a need to identify the determinants of variations at state level. We recommend strengthening of NHM in terms of funding and implementation.

Sparsity-based nonlinear reconstruction of optical parameters in two-photon photoacoustic computed tomography.

We present a new nonlinear optimization approach for the sparse reconstruction of single-photon absorption and two-photon absorption coefficients in the photoacoustic computed tomography (PACT). This framework comprises of minimizing an objective functional involving a least squares fit of the interior pressure field data corresponding to two boundary source functions, where the absorption coefficients and the photon density are related through a semi-linear elliptic partial differential equation (PDE) arising in PAT. Further, the objective functional consists of an L 1 regularization term that promotes sparsity patterns in absorption coefficients. The motivation for this framework primarily comes from some recent works related to solving inverse problems in acousto-electric tomography and current density impedance tomography. We provide a new proof of existence and uniqueness of a solution to the semi-linear PDE. Further, a proximal method, involving a Picard solver for the semi-linear PDE and its adjoint, is used to solve the optimization problem. Several numerical experiments are presented to demonstrate the effectiveness of the proposed framework.

The nuclear and mitochondrial sirtuins, Sirt6 and Sirt3, regulate each other's activity and protect the heart from developing obesity-mediated diabetic cardiomyopathy.

Sirtuins (Sirts) are implicated in regulating a myriad of biologic functions ranging from cell growth and metabolism to longevity. Here, we show that nuclear Sirt, Sirt6, and mitochondrial Sirt, Sirt3, regulate each other's activity and protect the heart from developing diabetic cardiomyopathy. We found that expression of both Sirt6 and Sirt3 was reduced in cardiomyocytes treated with palmitate and in hearts of mice fed with a high-fat, high-sucrose (HF-HS) diet to develop obesity and diabetes. Conversely, whole-body overexpressing Sirt6 transgenic (Tg.Sirt6) mice were protected from developing obesity and insulin resistance when fed with the same HF-HS diet. The hearts of Tg.Sirt6 mice were also protected from mitochondrial fragmentation and decline of Sirt3, resulting otherwise from HF-HS diet feeding. Mechanistic studies showed that Sirt3 preserves Sirt6 levels by reducing oxidative stress, whereas Sirt6 maintains Sirt3 levels by up-regulating nuclear respiratory factor 2 (Nrf2)-dependent Sirt3 gene transcription. We found that Sirt6 regulates Nrf2-mediated cardiac gene expression in 2 ways; first, Sirt6 suppresses expression of Kelch-like ECH-associated protein 1 (Keap1), a negative regulator of Nrf2, and second, Sirt6 binds to Nrf2 and antagonizes its interaction with Keap1, thereby stabilizing Nrf2 levels in cardiomyocytes. Together, these studies demonstrate that Sirt6 and Sirt3 maintain each other's activity and protect the heart from developing diabetic cardiomyopathy.-Kanwal, A., Pillai, V. B., Samant, S., Gupta, M., Gupta, M. P. The nuclear and mitochondrial sirtuins, Sirt6 and Sirt3, regulate each other's activity and protect the heart from developing obesity-mediated diabetic cardiomyopathy.

Comparison and evaluation of single-use LMA supreme versus the reusable proseal LMA in paralyzed patients undergoing surgery with controlled ventilation.

BACKGROUND AND AIMS: The objective of this prospective randomized blinded study was to assess the safety and efficacy of the laryngeal mask airway (LMA) Supreme as compared with the LMA Proseal. MATERIAL AND METHODS: A total of 60 patients were randomised into two groups to either receive a Proseal LMA (PLMA) or Supreme LMA (SLMA) for airway management. The primary outcome was to measure oropharyngeal leak pressure (OLP) in both groups. The secondary outcomes were the measurement of insertion time, insertion success rate, fibreoptic grading, intracuff pressure, ease of ventilation, and airway pressure on standard ventilatory settings and postoperative complications. RESULTS: Intracuff pressure increase after 60 minutes of induction was significantly higher in the PLMA group (PLMA 97.43 ± 11.03 cm of H2O and SLMA 75.17 ± 8.95 cm of H2O). OLP was recorded after device insertion, after 30 min and after 60 min in each group and was found to be 28.71 ± 2.97, 30.93 ± 2.87, and 31.93 ± 2.72 cm of H2O in PLMA and 24.84 ± 2.08, 26.73 ± 2.26, and 27.95 ± 2.55 cm of H2O in SLMA group, respectively. The mean OLP with the SLMA was significantly (p=<.001) lower than PLMA. All the other parameters were comparable in both groups. CONCLUSION: PLMA is better than SLMA as airway device to ventilate at higher airway pressure in paralyzed adult patients. On the basis of our study, we recommend Proseal over Supreme LMA.

Antibiotic-resistant Enterobacteriaceae in healthy gut flora: A report from north Indian semiurban community.

Background & objectives: Rampant use of ß-lactam antibiotics in both community and hospitals has transformed the human healthy intestinal gut flora into a reservoir of antibiotic-resistant organisms. This study was conducted to find the faecal presence of antibiotic-resistant Enterobacteriaceae in faecal samples in the community in north India. Methods: In this prospective study, 207 stool samples were collected from apparently healthy individuals residing in a semiurban community in Chandigarh, India, from August to October, 2015. Isolates belonging to family Enterobacteriaceae were identified using matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS), and antibiotic susceptibility was determined using Clinical Laboratory Standard Institute disc diffusion method. Detection of extended spectrum ß-lactamases (TEM, SHV, OXA-1, CTXM 1, CTXM 2, CTXM 9 and CTXM 8/25), carbapenemases (IMP, VIM and KPC) and New Delhi metallo-ß-lactamase was done by multiplex PCR. Results: Of the population studied, 55.5 per cent were females and 60 per cent were illiterate or had only primary education; 43.4 per cent individuals were aged <20 yr. Overall, 70.5 per cent of stool samples had antibiotic-resistant isolates. Maximum resistance was seen for cephalosporins (60.4%) followed by fluoroquinolones (41.5%). The multidrug-resistant (MDR) isolates were 2.4 per cent. The most commonly detected genes were TEM, SHV, OXA-1, CTXM-1, CTXM-2, CTXM-9 and CTXM-8/25 ß-lactamases. Escherichia coli was the most common resistant isolate, and TEM was the most common gene detected. Interpretation & conclusions: Overall, 70.5 per cent members of Enterobacteriaceae had antibiotic resistance in the community and 2.4 per cent were MDR. Higher resistance rates were observed for most commonly used drugs such as cephalosporins and fluoroquinolones. High rate of antibiotic-resistant Enterobacteriaceae in gut of healthy individuals points towards the need for active screening and prevention of dissemination.