Comparative metabolite profiling of rice contrasts reveal combined drought and heat stress signatures in flag leaf and spikelets.

Under semi-irrigated ecosystem, rice is often exposed to a combination of drought and heat stress, especially at the reproductive stage, leading to substantial yield loss. Combined stress studies are very limited in rice partly due to the difficulty in creating heat stress on a larger scale. Here, 24 cultivars with specific stress adaptive traits were phenotyped for spikelet sterility under combined stress using the natural summer temperatures and open drought phenotyping facility, simulating the field conditions. LC-MS/MS based metabolite profiling was performed in flag leaves and spikelets of three cultivars contrasting for spikelet sterility and source (leaf weight) treated to drought, heat and combined stress. Constitutively regulated metabolites, metabolic signatures common to all stresses, cultivars and tissues, metabolites common to both the tissues across the stresses and cultivars and metabolites common to each cultivar across the tissues and stresses were identified. Under combined stress, metabolites differentially accumulated between cultivars contrasting for spikelet sterility but similar for source and cultivars contrasting for both spikelet sterility and source have been identified. These metabolites would serve as markers towards improving combined stress tolerance of rice.

Thiourea mediated ROS-metabolites reprogramming restores root system architecture under arsenic stress in rice.

Arsenic (As) is a ubiquitous carcinogenic metalloid that enters into human food chain, through rice consumption. To unravel the conundrum of oxidative vs. reductive stress, the differential root-system architecture (RSA) was studied under As (a ROS producer) and thiourea (TU; a ROS scavenger) alone treatments, which indicated 0.80- and 0.74-fold reduction in the number of lateral roots (NLR), respectively compared with those of control. In case of As+TU treatment, NLR was increased by 4.35-fold compared with those of As-stress, which coincided with partial restoration of redox-status and auxin transport towards the root-tip. The expression levels of 16 ROS related genes, including RBOHC, UPB-1 C, SHR1, PUCHI, were quantified which provided the molecular fingerprint, in accordance with endogenous ROS signature. LC-MS based untargeted and targeted metabolomics data revealed that As-induced oxidative stress was metabolically more challenging than TU alone-induced reductive stress. Cis/trans-ferruloyl putrescine and γ-glutamyl leucine were identified as novel As-responsive metabolites whose levels were decreased and increased, respectively under As+TU than As-treated roots. In addition, the overall amino acid accumulation was increased in As+TU than As-treated roots, indicating the improved nutritional availability. Thus, the study revealed dynamic interplay between "ROS-metabolites-RSA", to the broader context of TU-mediated amelioration of As-stress in rice.

The Effect of Community-Based Nutritional Interventions on Children of Women Living With Human Immunodeficiency Virus in Rural India: A 2 × 2 Factorial Intervention Trial.

BACKGROUND: Malnutrition is a common clinical concern among children in low-income communities affected by human immunodeficiency virus (HIV). We examined the effect of a community-based nutritional intervention on anthropometric and clinical outcomes of children of women living with HIV in rural India. METHODS: We assigned women living with HIV and their child (oldest 3-8 years) to 1 of 4 programs: (1) community-based HIV care program, (2) program 1 + nutrition education, (3) program 1 + food supplement, and (4) all elements of programs 1-3. Study data were collected at baseline and months 6, 12, and 18. We applied mixed-effects modeling with restricted maximum likelihood estimation to examine changes in weight (all children) and CD4+ T-cell counts (children with HIV only). RESULTS: Overall, 600 mother-child pairs were enrolled (150/group) with 100% retention at follow-up visits. Approximately 20% of children were living with HIV. Children in program 4 had higher weight gain than those in programs 1, 2, and 3 at all time points (adjusted P < .001). We found a higher increase in CD4+ T cells across all time points among participants in programs 3 and 4 compared with program 1 (adjusted P < .001). Factorial analysis suggested a synergistic effect of combining nutrition education and food supplements for weight gain but not for increase in CD4+ T cells. CONCLUSIONS: A combination of nutrition education and food supplements provided to women living with HIV significantly increased weight and CD4+ T cells, and such interventions can be integrated into HIV-care programs in low-income settings.

Sustained Effect of a Community-based Behavioral and Nutrition Intervention on HIV-related Outcomes Among Women Living With HIV in Rural India: A Quasi-experimental Trial.

BACKGROUND: Women living with HIV (WLH) in rural communities face challenges to obtaining treatment and accurate disease-related information. Nutritional deficits exacerbate disease progression. SETTING: WLH were recruited from primary health centers in rural India. METHOD: A quasi-experimental trial of a comprehensive Accredited Social Health Activist (Asha)-supported intervention compared 4 distinct Asha-based programs [(1) standard education (SE) alone; (2) nutrition education (+NE); (3) nutrition supplements (+NS); or (4) nutrition education and nutrition supplements (+NENS)] on key disease and nutrition-related outcomes [CD4 count, body mass index (BMI), serum albumin, and hemoglobin]. Assessments occurred at baseline, and months 6 (immediately after intervention), 12, and 18. Multilevel modeling examined effects of program (group) over time. FINDINGS: Among 600 WLH enrolled (n = 150 per arm), mean age, CD4 count, and BMI (kg/m) were 34.31, 447.42, and 20.09, respectively, at baseline. At 18-month follow-up, program 4 (+NENS) experienced greatest improvements in CD4 counts compared with program 1 (+SE) [adjusted difference = 223.81, 95% confidence interval (CI): 170.29 to 277.32]. For BMI, programs 3 (+NS; adjusted difference = 2.33, 95% CI: 1.39 to 3.26) and 4 (+NENS; adjusted difference = 2.14, 95% CI: 1.17 to 3.12) exhibited greater gains compared with program 1 (+SE). Programs 3 and 4 were not significantly different from each other (adjusted difference = -0.18, 95% CI: -1.12 to 0.76). Hemoglobin and serum albumin also improved over time; program 4 (+NENS) exhibited the greatest gains. CONCLUSIONS: A low-cost Asha-supported behavioral and nutritional intervention improved outcomes for WLH. Gains were sustained at 18-month follow-up. Similar approaches may help improve HIV and other infectious disease-related outcomes in vulnerable populations.

Comparative analysis of the gut microbiota in centenarians and young adults shows a common signature across genotypically non-related populations.

Gut microbiota is among the factors that may be involved in healthy aging. Broader and geographically spread studies on gut microbiota of centenarians can help in identifying a common signature of longevity. We identified an endogamous Indian population with high centenarian prevalence. Here, we compared the gut microbiota composition and fecal metabolites of a centenarians group (˜100 years) with young people (25-45 years) of the region with the high centenarian prevalence and the nearby region of low centenarian prevalence to decipher microbial-related longevity signatures. Also, we compared our results with publicly available datasets of similar groups including 125 centenarians from three countries (Italy, Japan, China). Our comparative analysis resulted in higher biodiversity within Ruminococcaceae in centenarians, with respect to younger adults, irrespective of their nationality. We observed bacterial signatures that are common among extremely old people of different nationality. Comparative metabolites profiling identified the fecal metabolic signature of extreme aging in the Indian study population. Our analysis of the co-occurrence network and bimodal distribution of several taxa suggested the establishment of a pervasive change in the gut ecology during extreme aging. Our study might pave the way to develop gut microbiota based biomarkers for healthy aging.

Household Food Insecurity as Mediator of the Association Between Internalized Stigma and Opportunistic Infections.

Internalized HIV stigma can affect health outcomes, but the mechanism underlying this relationship is poorly understood. We investigated the potential pathways for the association between internalized stigma and opportunistic infections (OIs) among women living with HIV in rural India. We conducted a cross-sectional study involving in-person interviews with 600 participants. We modeled two outcome variables, total number of OIs and fungal dermatoses, which was the most frequently reported OI. Causal mediation analysis was performed to estimate the total effect, direct effect, and indirect effect through mediators while controlling for confounders. Food insecurity was a strong mediator of the association between internalized stigma and the number of OIs (70% of the total effect) and fungal dermatoses (83% of the total effect), while the indirect effect of stigma through adherence was minimal for both outcomes. Household food insecurity may be an important mediator of the impact of HIV-related stigma on opportunistic infections.

Chronic Disease Self-Management Challenges among Rural Women Living with HIV/AIDS in Prakasam, Andhra Pradesh, India: A Qualitative Study.

Rural women living with HIV/AIDS (WLHA) in India experience challenges self-managing HIV/AIDS in their rural communities. The purpose of this qualitative study was to explore factors influencing their care and antiretroviral treatment (ART) adherence. Themes that emerged from the qualitative focus groups among WLHA (N = 24) in rural Prakasam, Andhra Pradesh, India, included: (1) coming to know about HIV and other health conditions, (2) experiences being on ART, (3) challenges maintaining a nutritious diet, (4) factors affecting health care access and quality, and (5) seeking support for a better future. Chronic disease self-management in rural locales is challenging, given the number of barriers which rural women experience on a daily basis. These findings suggest a need for individual- and structural-level supports that will aid in assisting rural WLHA to self-manage HIV/AIDS as a chronic illness.

A method for comparative metabolomics in urine using high resolution mass spectrometry.

Developing a workflow for metabolite profiling from biological fluids using mass spectrometry is imperative to extract accurate information. In this study, urine samples from smokers (n=10) and nonsmokers (n=10) were analyzed using an ultrahigh performance liquid chromatography-high resolution mass spectrometry (UHPLC-HRMS) system. For the analysis, two different chromatographic methods [Reversed phase chromatography (RPC) and Hydrophilic interaction liquid chromatography (HILIC)], in two ionization modes (positive and negative) were used. Spiked reserpine (positive ion mode) or taurocholate (negative ion mode) were used for data extraction and normalization. Quality controls (QCs), prepared by pooling urine samples from both smokers and non-smokers (each n=10), were used to assess the reproducibility of the method. The final data output from SIEVE 2.2 after applying a cut-off for QC coefficient of variation (CV) <20% and p-value <0.05 showed 165, 83, 177 and 100 unique components in RP positive/negative, HILIC positive/negative modes, respectively. Statistical analysis showed clustering of the two groups and the QCs, while the variable importance in projection (VIP) scores for the top fifteen metabolites in each of the four modes indicated the metabolites most responsible for the differences. Application of the developed workflow for comparative metabolomic analysis of urine in different diseased models will be of great use in the field of clinical metabolomics.

ASHA-Life Intervention Perspectives Voiced by Rural Indian Women Living With AIDS.

In this focus group study, we explored the experiences of 16 rural women living with AIDS (WLA) who participated in the Asha-Life (AL) intervention to gain an understanding of the environmental, psychosocial, and cultural impact of the AL on their lives. Four themes emerged among AL participants: (a) the importance of tangible support, (b) need for social support, (c) ongoing challenges to accessing antiretroviral therapy (ART), and (d) perspectives on future programs. Our research findings support the development of future programs targeting mother-child dyads which emphasize nutritional knowledge, while reducing barriers to receiving ART, and physical, emotional, and financial support.

A quantitative metabolomics peek into planarian regeneration.

The fresh water planarian species Schmidtea mediterranea is an emerging stem cell model because of its capability to regenerate a whole animal from a small piece of tissue. It is one of the best model systems to address the basic mechanisms essential for regeneration. Here, we are interested in studying the roles of various amines, thiols and nucleotides in planarian regeneration, stem cell function and growth. We developed mass spectrometry based quantitative methods and validated the differential enrichment of 35 amines, 7 thiol metabolites and 4 nucleotides from both intact and regenerating planarians. Among the amines, alanine in sexual and asparagine in asexual are the highest (>1000 ng/mg) in the intact planarians. The levels of thiols such as cysteine and GSH are 651 and 1107 ng mg(-1) in planarians. Among the nucleotides, the level of cGMP is the lowest (0.03 ng mg(-1)) and the level of AMP is the highest (187 ng mg(-1)) in both of the planarian strains. We also noticed increasing levels of amines in both anterior and posterior regenerating planarians. The blastema from day 3 regenerating planarians also showed higher amounts of many amines. Interestingly, the thiol (cysteine and GSH) levels are well maintained during planarian regeneration. This suggests an inherent and effective mechanism to control induced oxidative stress because of the robust regeneration and stem cell proliferation. Like in intact planarians, the level of cGMP is also very low in regenerating planarians. Surprisingly, the levels of amines and thiols in head regenerating blastemas are ∼3 times higher compared to those for tail regenerating blastemas. Thus our results strongly indicate the potential roles of amines, thiols and nucleotides in planarian regeneration.

Physical and mental health of rural southern Indian women living with AIDS.

The purpose of this descriptive study is to highlight the physical and mental health symptoms of 68 rural women living with AIDS (WLA) in India, their compliance to antiretroviral therapy (ART) medication, and barriers to accessing health care within the past 6 months. Physical and mental health status was obtained by self-report, administered by questionnaire and physician-determined clinical assessment, as well as selected objective parameters. Findings revealed that while rural WLA had been on antiretroviral therapy for just under 2 years, they self-reported a high prevalence of physical symptoms, and more than half reported high levels of depressive symptoms and major barriers to accessing health care. CD4 levels, body weight, and basal metabolic rate were also low. While the rural and urban WLA faced similar health care challenges, the demographic characteristics of the rural women may make them more vulnerable, as they are less adherent to ART and slimmer than their urban counterparts.

Correlates of stigma among rural Indian women living with HIV/AIDS.

AIDS-related stigma has received increasing attention in the literature; however, little is known about the devastating impact it has on rural women living with AIDS (WLA) in India. This cross-sectional study (N = 68), analyzed from complete baseline data, identified a number of correlates of stigma among rural WLA in South India. Structured instruments were used to capture sociodemographic history, stigma, knowledge of HIV, depressive symptoms along with the recording of CD4 data. A higher level of felt stigma and more AIDS symptoms were related to avoidant coping, while fewer adherence strategies and lower support for antiretroviral therapy (ART) adherence were also associated with avoidant coping. These findings promote the need for support and resources for rural Indian WLA.

Impact of an Asha intervention on depressive symptoms among rural women living with AIDS in India: comparison of the Asha-Life and Usual Care program.

The purpose of this randomized pilot study is to conduct an intervention with 68 rural women living with AIDS to compare the effectiveness of two different programs on depressive symptoms. The trial was designed to assess the impact of the Asha-Life intervention engaging with an HIV-trained village woman, Asha (Accredited Social Health Activist), to participate in the care of women living with AIDS (WLA), along with other health care providers compared to a Usual Care group. Two high prevalence HIV/AIDS villages in rural Andhra Pradesh, which were demographically alike and served by distinct Public Health Centers, were selected randomly from a total of 16 villages. The findings of this study demonstrated that the Asha-Life participants significantly reduced their depressive symptom scores compared to the Usual Care participants. Moreover, women living with AIDS who demonstrated higher depressive symptom scores at baseline had greater reduction in their depressive symptoms than women with lower scores.

Correlates of Adherence among Rural Indian Women Living with HIV/AIDS.

In this prospective, randomized clinical trial, correlates of adherence to antiretroviral therapy (ART) were assessed using a baseline questionnaire among 68 rural women living with AIDS (WLA) in India. Unadjusted analyses revealed positive relationships of ART adherence with Hindu religion, and support from spouses and parents, whereas negative associations were found with depression, poor quality of life, and having ten or more HIV symptoms. Multiple linear regression analysis also revealed that WLA who were Hindu, not depressed, had ART support from spouses and parents, and perceived some benefit from ART were more adherent to ART than their respective counterparts. This study reveals the unique challenges which rural WLA experience and the need to mitigate these challenges early in ART treatment. Further, the findings enable the refinement of an intervention program which will focus on strengthening ART adherence among rural WLA.

Correlates of depression among rural women living with AIDS in Southern India.

Although depression may be commonly experienced by persons living with AIDS, it may be challenging for health care providers to identify persons who are suffering from depression symptoms, particularly if they are living in the more isolated rural areas of India. The purpose of this study is to assess correlates of depression among women living with AIDS in rural Andhra Pradesh, India. A total of 68 rural women living with AIDS (WLA) completed baseline data and were assessed by means of structured instruments. Regression modeling revealed that disclosure avoidance and making at least six health care visits in the last six months were all associated with depression. Further, living with a spouse was associated with lower depressive symptom scores. Stigma was not found to be associated with depression. Understanding correlates of depression can lead the way toward designing culturally-tailored interventions that can mitigate disclosure avoidance and improve the health of women. A more comprehensive health focus may be needed to empower the women to seek quality care for both physical health, as well as mental health, symptomatology.

Challenges experienced by rural women in India living with AIDS and implications for the delivery of HIV/AIDS care.

Researchers explored the barriers to AIDS care for rural women living with AIDS, and they investigated alternative delivery models to increase the women's adherence to antiretroviral therapy (ART). Community-based participatory research focus groups were conducted by the researchers with a convenience sample of 39 women living with AIDS from a primary health center (PHC) near Chennai, India, and with nurses, physicians, and Accredited Social Health Activists (Ashas), who are lay health care workers. The most prevalent barriers expressed by the women were sickness-related, psychological, financial issues with childcare, and distance, or transportation to the site. Women living with AIDS reviewed Ashas favorably.