Regulation of Anthrax Toxin-Specific Antibody Titers by Natural Killer T Cell-Derived IL-4 and IFNγ

Activation of Natural Killer-like T cells (NKT) with the CD1d ligand α-GC leads to enhanced production of anthrax toxin protective Ag (PA)-neutralizing Abs, yet the underlying mechanism for this adjuvant effect is not known. In the current study we examined the role of Th1 and Th2 type responses in NKT-mediated enhancement of antibody responses to PA. First, the contribution of IL-4 and IFNγ to the production of PA-specific toxin-neutralizing Abs was examined. By immunizing C57Bl/6 controls IL-4−/− mice and IFNγ−/− mice and performing passive serum transfer experiments, it was observed that sera containing PA-specific IgG1, IgG2b and IgG2c neutralized toxin in vitro and conferred protection in vivo. Sera containing IgG2b and IgG2c neutralized toxin in vitro but were not sufficient for protection in vivo. Sera containing IgG1 and IgG2b neutralized toxin in vitro and conferred protection in vivo. IgG1 therefore emerged as a good correlate of protection. Next, C57Bl/6 mice were immunized with PA alone or PA plus a Th2-skewing α-GC derivative known as OCH. Neutralizing PA-specific IgG1 responses were modestly enhanced by OCH in C57Bl/6 mice. Conversely, IgG2b and IgG2c were considerably enhanced in PA/OCH-immunized IL-4−/− mice but did not confer protection. Finally, bone marrow chimeras were generated such that NKT cells were unable to express IL-4 or IFNγ. NKT-derived IL-4 was required for OCH-enhanced primary IgG1 responses but not recall responses. NKT-derived IL-4 and IFNγ also influenced primary and recall IgG2b and IgG2c titers. These data suggest targeted skewing of the Th2 response by α-GC derivatives can be exploited to optimize anthrax vaccination

Where to deliver? Analysis of choice of delivery location from a national survey in India

<p>Abstract</p> <p>Background</p> <p>In order to reduce maternal mortality, the Indian government has increased its commitment to institutional deliveries. We assess the determinants of home, private and public sector utilization for a delivery in a Western state.</p> <p>Methods</p> <p>Cross sectional analyses of the National Family Health Survey – 2 dataset.</p> <p>Setting</p> <p>Maharashtra state. The dataset had a sample size of 5391 ever-married females between the ages of 15 to 49 years. Data were abstracted for the most recent birth (n = 1510) and these were used in the analyses. Conceptual framework was the Andersen Behavioral Model. Multinomial logistic regression analyses was conducted to assess the association of predisposing, enabling and need factors on use of home, public or private sector for delivery.</p> <p>Results</p> <p>A majority delivered at home (n = 559, 37%); with private and public facility deliveries accounting for 32% (n = 493) and 31% (n = 454) respectively. For the choice set of home delivery versus public facility, women with higher birth order and those living in rural areas had greater odds of delivering at home, while increasing maternal age, greater media exposure, and more then three antenatal visits were associated with greater odds of delivery in a public facility. Maternal and paternal education, scheduled caste/tribe status, and media exposure were statistically significant predictors of the choice of public versus private facility delivery.</p> <p>Conclusion</p> <p>As India's economy continues to grow, the private sector will continue to expand. Given the high household expenditures on health, the government needs to facilitate insurance schemes or provide grants to prevent impoverishment. It also needs to strengthen the public sector so that it can return to its mission of being the safety net.</p

The relation between the producer and consumer price indices: a two-country study

© 2017, Macmillan Publishers Ltd., part of Springer Nature. Marketing managers are often in a dilemma about which pricing index to rely on while calculating the annual increase in the prices for their product. To provide insights that can reduce this dilemma, a critical comparison of the Producer Price index and consumer price index is called for. In this study, the relation between the Producer Price Index (PPI) and Consumer Price Index (CPI) was investigated through a comparison between Turkey and UK. Unlike many other previous studies, this study tried to determine the dominant pricing approach in an economy by examining the relation between the producer and consumer prices. In this context, VAR, impulse-response, variance decomposition, and Granger causality tests were used for the analyses of time series data. The results of study showed that there was bidirectional causality between the producer and consumer prices in both countries. Therefore, it was asserted that businesses in both countries generally apply mixed pricing approach. The results thus provide some interesting insights that can aid marketing managers in their pricing decisions

Ifugao males, learning and teaching for the improvement of maternal and child health status in the Philippines: an evaluation of a program

<p>Abstract</p> <p>Background</p> <p>Improving Maternal and Child Health (MCH) is a prioritized global agenda in achieving the United Nations Millennium Development Goal 5. In this challenge, involving males has been an important agenda, and a program with such intent was conducted in <it>Alfonso Lista, Ifugao</it>, of the Philippines. The objectives of this study were: (1) to evaluate the effectiveness in knowledge, attitude, and practice before and after a MCH session; (2) to evaluate the session's effectiveness in relation to socio-demographic characteristics; and (3) to examine if males who have learned about MCH topics can teach another group of males.</p> <p>Methods</p> <p>A male community representative who received a lecture from the health office staff was assigned to teach a group of community males [Group 1, N = 140] in 5 sessions, using educational materials. 10 male volunteers from Group 1 then taught a different group of males [Group 2, N = 105] in their own <it>barangays </it>(villages). To evaluate its effectiveness, a self-administered questionnaire survey pertaining knowledge, attitude and practice regarding MCH was conducted at three different time points: before the session (Time 1, T1), after the session (Time 2, T2), and 3 months following the session (Time 3, T3). A repeated measures analysis of variance was conducted to test for changes over time and its interaction effect between specific socio-demographic variables.</p> <p>Results</p> <p>In Group 1, there was a significant positive increase in knowledge score over time at T1-T2 and T1-T3 (<it>p </it>< 0.001). For attitude, the score increased only at T1-T2 (<it>p </it>= 0.027). The effectiveness in knowledge and attitude did not vary by socio-demographic characteristics. As for practice, majority of the participants reported that they had talked about MCH topics in their community and assisted a pregnant woman in some ways. A comparison between Group 1 and Group 2 revealed that Group 2 had similar effectiveness as Group 1 in knowledge improvement immediately after the session (<it>p </it>< 0.001), but no such improvement in the attitude score.</p> <p>Conclusion</p> <p>Although the change in attitude needs further assessment, this strategy of continuous learning and teaching of MCH topics within community males is shown to improve knowledge and has a potential to uplift the MCH status, including the reduction of maternal deaths, in <it>Alfonso Lista, Ifugao, Philippines</it>.</p

What explains Cambodia’s success in reducing child stunting-2000-2014?

In many developing countries, high levels of child undernutrition persist alongside rapid economic growth. There is considerable interest in the study of countries that have made rapid progress in child nutrition to uncover the driving forces behind these improvements. Cambodia is often cited as a success case having reduced the incidence of child stunting from 51% to 34% over the period 2000 to 2014. To what extent is this success driven by improvements in the underlying determinants of nutrition, such as wealth and education, (“covariate effects”) and to what extent by changes in the strengths of association between these determinants and nutrition outcomes (“coefficient effects”)? Using determinants derived from the widely-applied UNICEF framework for the analysis of child nutrition and data from four Demographic and Health Surveys datasets, we apply quantile regression based decomposition methods to quantify the covariate and coefficient effect contributions to this improvement in child nutrition. The method used in the study allows the covariate and coefficient effects to vary across the entire distribution of child nutrition outcomes. There are important differences in the drivers of improvements in child nutrition between severely stunted and moderately stunted children and between rural and urban areas. The translation of improvements in household endowments, characteristics and practices into improvements in child nutrition (the coefficient effects) may be influenced by macroeconomic shocks or other events such as natural calamities or civil disturbance and may vary substantially over different time periods. Our analysis also highlights the need to explicitly examine the contribution of targeted child health and nutrition interventions to improvements in child nutrition in developing countries

Socio-Economic Inequalities in the Use of Postnatal Care in India

OBJECTIVES: First, our objective was to estimate socio-economic inequalities in the use of postnatal care (PNC) compared with those in the use of care at birth and antenatal care. Second, we wanted to compare inequalities in the use of PNC between facility births and home births and to determine inequalities in the use of PNC among mothers with high-risk births. METHODS AND FINDINGS: Rich-poor ratios and concentration indices for maternity care were estimated using the third round of the District Level Household Survey conducted in India in 2007-08. Binary logistic regression models were used to examine the socio-economic inequalities associated with use of PNC after adjusting for relevant socio-economic and demographic characteristics. PNC for both mothers and newborns was substantially lower than the care received during pregnancy and child birth. Only 44% of mothers in India at the time of survey received any care within 48 hours after birth. Likewise, only 45% of newborns received check-up within 24 hours of birth. Mothers who had home births were significantly less likely to have received PNC than those who had facility births, with significant differences across the socio-economic strata. Moreover, the rich-poor gap in PNC use was significantly wider for mothers with birth complications. CONCLUSIONS: PNC use has been unacceptably low in India given the risks of mortality for mothers and babies shortly after birth. However, there is evidence to suggest that effective use of pregnancy and childbirth care in health facilities led to better PNC. There are also significant socio-economic inequalities in access to PNC even for those accessing facility-based care. The coverage of essential PNC is inadequate, especially for mothers from economically disadvantaged households. The findings suggest the need for strengthening PNC services to keep pace with advances in coverage for care at birth and prenatal services in India through targeted policy interventions

Complex Calculations: How Drug Use During Pregnancy Becomes a Barrier to Prenatal Care

Pregnant women who use drugs are more likely to receive little or no prenatal care. This study sought to understand how drug use and factors associated with drug use influence women’s prenatal care use. A total of 20 semi-structured interviews and 2 focus groups were conducted with a racially/ethnically diverse sample of low-income women using alcohol and drugs in a California county. Women using drugs attend and avoid prenatal care for reasons not connected to their drug use: concern for the health of their baby, social support, and extrinsic barriers such as health insurance and transportation. Drug use itself is a barrier for a few women. In addition to drug use, women experience multiple simultaneous risk factors. Both the drug use and the multiple simultaneous risk factors make resolving extrinsic barriers more difficult. Women also fear the effects of drug use on their baby’s health and fear being reported to Child Protective Services, each of which influence women’s prenatal care use. Increasing the number of pregnant women who use drugs who receive prenatal care requires systems-level rather than only individual-level changes. These changes require a paradigm shift to viewing drug use in context of the person and society and acceptance of responsibility for unintended consequences of public health bureaucratic procedures and messages about effects of drug use during pregnancy

Home birth and barriers to referring women with obstetric complications to hospitals: a mixed-methods study in Zahedan, southeastern Iran

<p>Abstract</p> <p>Background</p> <p>One factor that contributes to high maternal mortality in developing countries is the delayed use of Emergency Obstetric-Care (EmOC) facilities. The objective of this study was to determine the factors that hinder midwives and parturient women from using hospitals when complications occur during home birth in Sistan and Baluchestan province, Iran, where 23% of all deliveries take place in non- hospital settings.</p> <p>Methods</p> <p>In the study and data management, a mixed-methods approach was used. In the quantitative phase, we compared the existing health-sector data with World Health Organization (WHO) standards for the availability and use of EmOC services. The qualitative phase included collection and analysis of interviews with midwives and traditional birth attendants and twenty-one in-depth interviews with mothers. The data collected in this phase were managed according to the principles of qualitative data analysis.</p> <p>Results</p> <p>The findings demonstrate that three distinct factors lead to indecisiveness and delay in the use of EmOC by the midwives and mothers studied. Socio-cultural and familial reasons compel some women to choose to give birth at home and to hesitate seeking professional emergency care for delivery complications. Apprehension about being insulted by physicians, the necessity of protecting their professional integrity in front of patients and an inability to persuade their patients lead to an over-insistence by midwives on completing deliveries at the mothers' homes and a reluctance to refer their patients to hospitals. The low quality and expense of EmOC and the mothers' lack of health insurance also contribute to delays in referral.</p> <p>Conclusions</p> <p>Women who choose to give birth at home accept the risk that complications may arise. Training midwives and persuading mothers and significant others who make decisions about the value of referring women to hospitals at the onset of life-threatening complications are central factors to increasing the use of available hospitals. The hospitals must be safe, comfortable and attractive environments for parturition and should give appropriate consideration to the ethical and cultural concerns of the women. Appropriate management of financial and insurance-related issues can help midwives and mothers make a rational decision when complications arise.</p

Bacillus anthracis Lethal Toxin Disrupts TCR Signaling in CD1d-Restricted NKT Cells Leading to Functional Anergy

Exogenous CD1d-binding glycolipid (α-Galactosylceramide, α-GC) stimulates TCR signaling and activation of type-1 natural killer–like T (NKT) cells. Activated NKT cells play a central role in the regulation of adaptive and protective immune responses against pathogens and tumors. In the present study, we tested the effect of Bacillus anthracis lethal toxin (LT) on NKT cells both in vivo and in vitro. LT is a binary toxin known to suppress host immune responses during anthrax disease and intoxicates cells by protective antigen (PA)-mediated intracellular delivery of lethal factor (LF), a potent metalloprotease. We observed that NKT cells expressed anthrax toxin receptors (CMG-2 and TEM-8) and bound more PA than other immune cell types. A sub-lethal dose of LT administered in vivo in C57BL/6 mice decreased expression of the activation receptor NKG2D by NKT cells but not by NK cells. The in vivo administration of LT led to decreased TCR-induced cytokine secretion but did not affect TCR expression. Further analysis revealed LT-dependent inhibition of TCR-stimulated MAP kinase signaling in NKT cells attributable to LT cleavage of the MAP kinase kinase MEK-2. We propose that Bacillus anthracis–derived LT causes a novel form of functional anergy in NKT cells and therefore has potential for contributing to immune evasion by the pathogen