Early childhood height is a determinant of young adult stature in rural Nepal.

BACKGROUND: Does preschool height predict adult stature in undernourished settings? The extent to which preschool length or height forecasts young adult stature is unclear in chronically undernourished populations. METHODS: In 2006-8, we assessed height in a cohort of 2074 young adults, aged 16-23 years, in rural Nepal who, as preschoolers (≤ 4 year), were measured at baseline and again 16 months later during a vitamin A supplementation trial in 1989-91. We assessed by linear regression the ability of preschool length (L, measured < 24 mo) or height (Ht, 24-59 mo), at each year of age to predict 16-23 year old height, adjusted for month of young adult age, interval duration (in months), caste, preschool weight-for-height z-score and, in young women, time since menarche, marriage status and pregnancy history. RESULTS: Young women were a mean of 0.81, 1.11, 0.82, 0.24, 0.44 cm taller (all p < 0.01) and young men, 0.84, 1.18, 0.74, 0.64 and 0.48 cm taller (all p < 0.001) per cm of attained L/Ht at each successive preschool year of age and, overall, were 2.04 and 2.40 cm taller for each unit increase in preschool L/Ht z-score (L/HAZ) (both p < 0.001). Coefficients were generally larger for 16-month follow-up measurements. The percent of young adult height attained by children with normal L/HAZ (>-1) increased from 38-40% mid-infancy to ∼ 69-74% by 6 years of age. By 3-6 years of age heights of stunted children (L/HAZ<-2) were consistently ∼ 4-7% lower in their young adult height versus normal statured children. There was no effect of preschool vitamin A receipt. CONCLUSIONS: Shorter young children become shorter adults but predictive effects can vary by sex, age assessed, and may be influenced by year or season of measurement.

Impact of Suaahara, an at-scale multisectoral nutrition programme, on health workers' maternal and child health, and nutrition knowledge and skills in Nepal.

Suaahara, an at-scale multisectoral nutrition programme in Nepal, aimed to advance knowledge and skills of frontline health workers to improve the quality of nutrition and health services at health facility and community levels. This study assessed the impact of Suaahara interventions on knowledge and skills of health facility workers and Female Community Health Volunteers (FCHVs). The study used a quasi-experimental design in which four Suaahara intervention districts were compared with pair-matched comparison districts. One health facility worker and three FCHVs from each survey cluster were included. Baseline survey consisted of 93 health facility workers (2015) and 118 FCHVs (2012), and endline survey (2022) consisted of 40 health facility workers and 120 FCHVs. Difference-in-differences regression models employing intent-to-treat analysis, accounting for clustering at the district level, assessed the impact of intervention. The intervention, relative to comparison, had no effect on health facility workers' knowledge. There was a positive effect, however, on FCHVs' knowledge in intervention relative to comparison areas on exclusive breastfeeding, timing of introduction of complementary feeding, sick child feeding and growth monitoring and promotion (GMP) for children under 2 years. Health facility workers and FCHVs in intervention versus comparison districts had higher endline scores for skills related to measuring the weight of children and pregnant women, measuring the height/length of children, conducting GMP for children under 2 years and identifying malnourished children. Suaahara interventions improved the capacity of health workers, particularly nutrition-related knowledge among FCHVs and GMP-related skills of both health facility workers and FCHVs.

Impact of Suaahara, an integrated nutrition programme, on maternal and child nutrition at scale in Nepal.

Suaahara was an innovative, complex, multi-sectoral, large-scale, nutrition programme in Nepal to increase exposure to nutrition-related information and services, improve nutrition-related knowledge and practices among pregnant women and mothers of infants and young children, and improve their nutrition. This study evaluated the effectiveness of Suaahara to improve nutrition and nutrition-related practices by comparing changes over 10 years between intervention and comparison districts. The samples of households at baseline in 2012 and endline in 2022 were 2040 and 2480, respectively, from 120 old wards. The impact was estimated using intent-to-treat regression models in which survey year, arm and their interaction were fixed effects, accounting for district clustering, with the interaction estimating differences between arms in changes over time. The intervention, relative to comparison, reduced maternal underweight by 8.43 percentage points (p < 0.001), consistent with improved maternal and fetal condition that was manifested as the greater length of 0.761 z-scores (p = 0.004) of infants 0-5.9 months. Complementary feeding practices with children between 6 and 23.9 months of age improved more in the intervention than comparison districts: child dietary diversity by 0.294 food groups (p = 0.072) and minimum dietary diversity by 9.51 percentage points (p = 0.028), feeding sick child more (p = 0.002) and administering oral rehydration solution and zinc for diarrhoea (p = 0.057) by about 17 percentage points each, and minimum meal frequency (p = 0.004) and minimum acceptable diet (p = 0.022) by about 15 percentage points each. Substantial impacts were demonstrated despite political restructuring, earthquakes, and other major challenges that Nepal and Suaahara faced and limitations in statistical power because of the reduced number of districts that then could be included in the study. Registered at clinicaltrials.gov with identifier NCT05448287.

Evaluating preschool linear growth velocities: an interim reference illustrated in Nepal.

OBJECTIVE: An annualised linear growth velocity (LGV) reference can identify groups of children at risk of growing poorly. As a single velocity reference for all preschool ages does not exist, we present an interim tool, derived from published, normative growth studies, for detecting growth faltering, illustrating its use in Nepali preschoolers. DESIGN: The WHO Child Growth Velocity Standard was adapted to derive 12-month increments and conjoined to the Tanner-Whitehouse Height Velocity Reference data yielding contiguous preschool linear growth annualised velocities. Linear restricted cubic spline regressions were fit to generate sex-specific median and standard normal deviate velocities for ages 0 through 59 months. LGV Z-scores (LGVZ) were constructed, and growth faltering was defined as LGVZ < ­2. SETTING: Use of the reference was illustrated with data from Nepal's Tarai region. PARTICIPANTS: Children contributing the existing growth references and a cohort of 4276 Nepali children assessed from 2013 to 2016. RESULTS: Fitted, smoothed LGV reference curves displayed monotonically decreasing 12-month LGV, exemplified by male/female annual medians of 26·4/25·3, 12·1/12·7, 9·1/9·4, 7·7/7·8 and 7/7 cm/years, starting at 0, 12, 24, 36 and 48 months, respectively. Applying the referent, 31·1 %, 28·6 % and 29·3 % of Nepali children <6, 6­11 and 12­23 months of age, and ∼6 % of children 24­59 months, exhibited growth faltering. Under 24 months, faltering velocities were more prevalent in girls (34·4 %) than boys (25·3 %) (P < 0·05) but comparable (∼6 %) in older preschoolers. CONCLUSIONS: A LGV reference, concatenated from extant data, can identify preschool groups at-risk of growth faltering. Application and limitations are discussed.

Malnutrition matters: Association of stunting and underweight with early childhood development indicators in Nepal.

Malnutrition is a threat to optimal child development, with its occurrence during foetal and infancy stages associated with poor cognitive, motor and socio-emotional skills. However, information on the effects of various types of malnutrition on early childhood development (ECD) is limited in Nepal. To assess the association of stunting, wasting and underweight (three prominent forms of malnutrition) with the four domains of the ECD index (literacy-numeracy, physical, social-emotional and learning development) among children 36-59 months of age, we conducted an adjusted logistic regression using Nepal's national household Multiple Indicator Cluster Survey (MICS) 2019 data set. The study sample consisted of children aged 36-59 months (n = 2871). Children were considered developmentally on track if they met criteria in each of the four ECD domains. Regarding ECD status of children 36-59 months old, 35% of children were not developmentally on track for the ECD index. The adjusted odds ratio indicated that stunting was associated with lower odds of not being developmentally on track according to the ECD index as well as the literacy-numeracy, physical and learning domains of the ECD index. Likewise, underweight was associated with lower odds of not being developmentally on track according to the ECD index, primarily for ECD domains of literacy-numeracy, physical and learning. Notably, no association between wasting and ECD indicators was observed. Children's nutrition status impacts child development outcomes. Adding ECD interventions, such as responsive and stimulating caregiving, within nutrition programmes among children who are stunted and underweight could improve child development outcomes.

A review of the maternal iron and folic acid supplementation programme in Nepal: Achievements and challenges.

In the late 1990s, an estimated 75% of pregnant women in Nepal were anaemic. Although iron and folic acid (IFA) supplements were available free of charge, coverage among pregnant women was very low. In response, the Government of Nepal launched the Iron Intensification Programme (IIP) in 2003 to improve the coverage of IFA supplementation and anthelminthic treatment during pregnancy, as well as promote the utilization of antenatal care. This review examined how the IIP programme contributed to Nepal's success in increasing the consumption of IFA supplements during pregnancy. Nepal's cadre of Female Community Health Volunteers were engaged in the IIP to support the community-based distribution of IFA supplements to pregnant women and complement IFA distribution through health facilities and outreach services. As a result, the country achieved a fourfold increase in the proportion of women who took IFA supplements during pregnancy between 2001 and 2016 (from 23% to 91%) and a 12-fold increase in the proportion who took IFA supplements for at least 90 days during pregnancy (from 6% to 71%). The increase in coverage of IFA supplements accompanied an increase in the coverage of antenatal care during the same period. By 2016, the prevalence of anaemia in pregnant women decreased to 46%, highlighting the need to tackle other causes of anaemia and improve haemoglobin concentration before pregnancy, while maintaining the successful efforts to reach pregnant women with IFA supplements at the community level.

Trends in and determinants of visiting private health facilities for maternal and child health care in Nepal: comparison of three Nepal demographic health surveys, 2006, 2011, and 2016.

BACKGROUND: Maternal and child health care services are available in both public and private facilities in Nepal. Studies have not yet looked at trends in maternal and child health service use over time in Nepal. This paper assesses trends in and determinants of visiting private health facilities for maternal and child health needs using nationally representative data from the last three successive Nepal Demographic Health Surveys (NDHS). METHODS: Data from the NDHS conducted in 2006, 2011, and 2016 were used. Maternal and child health-seeking was established using data on place of antenatal care (ANC), place of delivery, and place of treatment for child diarrhoea and fever/cough. Logistic regression models were fitted to identify trends in and determinants of health-seeking at private facilities. RESULTS: The results indicate an increase in the use of private facilities for maternal and child health care over time. Across the three survey waves, women from the highest wealth quintile had the highest odds of accessing ANC services at private health facilities (AOR = 3.0, 95% CI = 1.53, 5.91 in 2006; AOR = 5.6, 95% CI = 3.51, 8.81 in 2011; AOR = 6.0, 95% CI = 3.78, 9.52 in 2016). Women from the highest wealth quintile (AOR = 3.3, 95% CI = 1.54, 7.09 in 2006; AOR = 7.3, 95% CI = 3.91, 13.54 in 2011; AOR = 8.3, 95% CI = 3.97, 17.42 in 2016) and women with more years of schooling (AOR = 1.2, 95% CI = 1.17, 1.27 in 2006; AOR = 1.1, 95% CI = 1.04, 1.14 in 2011; AOR = 1.1, 95% CI = 1.07, 1.16 in 2016) were more likely to deliver in private health facilities. Likewise, children belonging to the highest wealth quintile (AOR = 8.0, 95% CI = 2.43, 26.54 in 2006; AOR = 6.4, 95% CI = 1.59, 25.85 in 2016) were more likely to receive diarrhoea treatment in private health facilities. CONCLUSIONS: Women are increasingly visiting private health facilities for maternal and child health care in Nepal. Household wealth quintile and more years of schooling were the major determinants for selecting private health facilities for these services. These trends indicate the importance of collaboration between private and public health facilities in Nepal to foster a public private partnership approach in the Nepalese health care sector.

Can Nepal achieve nutritional targets by 2030? A trend analysis of childhood undernutrition in Nepal from 2001 to 2016.

OBJECTIVE: This study assesses the prevalence of childhood undernutrition from 2001 to 2016 and estimate projections of undernutrition for 2016-2030 in Nepal. DESIGN: The study used data from four rounds of a cross-sectional survey of Nepal Demographic and Health Survey (NDHS) conducted in 2001, 2006, 2011 and 2016. Descriptive analyses were conducted to calculate prevalence, binary logistic regression was used to test the significance of trends over time and autoregressive integrated moving average model was used to forecast the prevalence of childhood undernutrition. SETTINGS: The children and household member datasets from four NDHS were merged to assess the trends of childhood undernutrition in Nepal. PARTICIPANTS: A total of 16 613 children (8399 male and 8214 female) under 5 years of age were selected for anthropometric measurements using a stratified cluster random sampling method. RESULTS: Overall results show a decline in prevalence of stunting from 57·2 % to 35·8 % (P < 0·001), underweight from 42·7 % to 27 % (P < 0·001) and wasting from 11·2 % to 9·7 % (P < 0·05) from 2001 to 2016. However, different population subgroups have a higher prevalence of undernutrition than national average. Further, the analyses show that the prevalence of stunting will decline to 14·3 % and wasting to 8·4 % by 2030. CONCLUSION: A remarkable decrease in the prevalence of stunting and underweight has been observed over the last 15 years. Nepal is likely to achieve the nutritional targets for stunting but not for wasting by 2030. Given large subpopulation variations, further improvement in undernutrition require more specific, targeted and localised programmes.

Does exposure of mass media associate with utilisation of ANC services? A trend analysis from Nepal demographic and health surveys.

The study analysed antenatal care (ANC) services usage trends related to exposure to mass media based upon data from three Nepal Demographic and Health Surveys [NDHS] conducted in 2006, 2011, and 2016. Total 12,212 women aged 15-49 having live births within five years preceding each survey included in the study. Most independent variables were found to be associated with utilisation of ANC services. For example, exposure to TV illustrated an increasing services trend. Seventy-three percent of the women had exposure to Radio followed by TV (65%), and newspaper (25%). All three media were significantly associated with ANC services in all surveys (p < 0.05). High exposure to Newspapers were (2.5 times, 95%CI: 1.93-3.19), Radio (1.3 times, 95%CI: 1.13-1.46), and TV (1.6 times, 95%CI: 1.36-1.76) more likely to result in adequate (≥4) ANC visits. Age and age at marriage; caste and educational status of women; place of residence; wealth status; and women's decision-making autonomy were significant predictors for adequate ANC visits. ANC services utilisation trends increased gradually, but not satisfactory. Most socio-demographic variables were also significant predictors for utilizing ANC services. All these predictors should be used to guide ANC services promotion policies and interventions.

Associations between parents' exposure to a multisectoral programme and infant and young child feeding practices in Nepal.

In Nepal, an at-scale, multisectoral programme-Suaahara (2011-2023)-aims to improve nutrition behaviours. Suaahara II (2016-2023) transitioned from a mother/child dyad focus to explicitly targeting all family members. Evidence is scant, however, regarding how exposure by men to social and behaviour change interventions relates to nutrition outcomes. This study uses a 2019 cross-sectional monitoring dataset to test associations between maternal and male household head exposure to Suaahara II interventions (interacting with a frontline worker, participating in a community event or listening to the Bhanchhin Aama radio programme) and adoption of three infant and young child feeding practices: minimum dietary diversity, minimum acceptable diet and sick child feeding, in households with a child under 2 years (n = 1827). Maternal exposure to Suaahara II had a positive association with minimum dietary diversity (OR: 1.71, 95% CI [1.27, 2.28], P < 0.001), minimum acceptable diet (OR: 1.60, 95% CI [1.19, 2.14], P = 0.002) and increased feeding to a sick child (OR: 2.11, 95% CI [1.41, 3.17], P < 0.001). Male household head exposure was only associated with increased feeding to a sick child (OR: 2.21, 95% CI [1.27, 3.84], P = 0.005). Among households with an exposed mother, having an exposed male household head nearly tripled the odds of appropriate sick child feeding (OR: 2.90, 95% CI [1.57, 5.34], P = 0.001) but was not significantly associated with the other two outcomes. These findings suggest that the relationships between exposure to nutrition programmes and outcomes are complex and further research is needed to understand variation by family member, behavioural outcome and context.

Intimate partner violence and nutritional status among nepalese women: an investigation of associations.

BACKGROUND: Malnutrition among women in Nepal persists as a major public health burden. Global literature suggests that domestic violence may have a negative impact on women's nutritional status. The contribution of intimate partner violence (IPV) to increased stress levels, poor self-care including the consumption of less food and, in turn, malnutrition has been documented. However, there is little empirical evidence on IPV and its relationship with women's nutritional status in Nepal and thus, this paper assesses these associations. METHODS: We used data on non-pregnant married women (n = 3293) from the 2016 Nepal Demographic and Health Survey (NDHS). The primary exposure variable was whether the women had ever experienced physical, sexual, or emotional violence or controlling behaviours by a current or former partner, based on her responses to the NDHS domestic violence questions. The primary outcome variables were three indicators of malnutrition: under-weight (BMI < 18.5), over-weight (BMI > 25), and anemia (Hb < 11.0 g dL). We used logistic and multinomial regression models, adjusted for potential socio-demographic and economic confounders, as well as clustering, to examine associations between IPV exposure and malnutrition. RESULTS: Approximately 44% of women had experienced at least one of the four types of IPV. Among them, around 16, 25%. and 44% were underweight, overweight, or anemic, respectively, compared to 13, 29, and 35% of women never exposed to IPV. We did not find any associations between underweight and any of the four types of IPV. Overweight was associated with physical violence (adjusted RRR = 0.67, P < 0.01, CI = 0.50-0.88) and severe physical violence (adjusted RRR = 0.53, P < 0.05, CI = 0.32-0.88) Controlling behaviors were associated with anemia (adjusted RRR = 1.31, P < 0.01, CI = 1.11-1.54). CONCLUSIONS: Among married Nepalese women, physical violence appears to be a risk factor for one's weight and controlling behaviors for one's anemia status. Additional, rigorous, mixed-methods research is needed to understand the reporting of IPV and what relationships do or do not exist between IPV experience and nutrition both in Nepal and in other settings.

Parental depression and nutrition: findings from a cross-sectional household survey in Nepal.

OBJECTIVE: The present study aims to assess associations between parental depression and parental and child nutritional status and diets in Nepal. DESIGN: A cross-sectional survey conducted from June to September 2017. SETTING: This monitoring survey was conducted in sixteen of forty-two Suaahara intervention districts spanning mountains, hills and plains in Nepal. Multi-stage cluster sampling was used to sample communities in this survey. PARTICIPANTS: Women and men with a child 6-59 months of age were randomly selected (n 3158 mothers and children; n 826 fathers). RESULTS: Overall, 36 % of mothers, 37 % of fathers and 55 % of children met minimum dietary diversity, indicating that they consumed foods from at least four of seven food groups (children) and at least five of ten food groups (adults) in the 24 h prior to the interview. The percentage of children stunted, wasted and underweight was 28, 11 and 23, respectively. Only 5 % of mothers and 3 % of fathers screened positive for moderate or severe depression (Patient Health Questionnaire-9 score ≥ 10). In adjusted models, we found maternal depression was positively associated with maternal underweight (OR = 1·48, 95 % CI 1·01, 2·17). Maternal and paternal depression, however, were not associated with other indicators of anthropometric status or dietary diversity. CONCLUSIONS: Maternal and paternal depression, measured by the Patient Health Questionnaire-9, were not associated with dietary diversity or anthropometric status of fathers or children in Nepal, whereas depressed mothers were at increased risk of being underweight. Additional studies are needed to further assess relationships between mental health and nutritional outcomes.

Evaluating the integration of chronic care elements in primary health care for people with mental illness: a longitudinal study in Nepal conducted among primary health care workers.

BACKGROUND: Despite many important developments in the global mental health arena in the past decade, many people with mental health problems still do not have access to good quality mental health care. The aim of this study was to evaluate the perceived impact of a mental health care package (MHCP) in integrating chronic care elements in primary health care for people with mental illness. METHODS: A controlled pre-post study design was used in 20 primary health care facilities in Chitwan, Nepal. We compared 10 health facilities that had implemented a MHCP (intervention group), with 10 health facilities that had not implemented the MHCP (comparative control group) but provided regular physical health services. We administered the Assessment of Chronic Illness Care (ACIC) tool on a group basis within all 20 health facilities among 37 health workers. Data was collected at three time points; at baseline, midline (at 13 months from baseline) and end line (at 25 months from baseline). RESULTS: From baseline to end line, we see a notable shift in the level of support reported by the intervention health facilities compared to those in the comparative control group. While at baseline 10% of the intervention health facilities had basic support for the implementation of chronic illness care, at the end line, 90% of the intervention group reported having reasonable support with the remaining 10% of the intervention facilities reporting that they had full support. In contrast, 20% of the health facilities in the comparative control group at end line still reported having limited support for the implementation of chronic illness care, with the remaining 80% only managing to shift to the next level which is basic support. CONCLUSIONS: These findings suggest that training and supervision of primary health care workers in the implementation of MHCP interventions can lead to strengthening of the system to better address the needs of patients with chronic mental health problems. However, substantial financial and coordination inputs are needed to implement the MHCP. The comparative control group also demonstrated improvements, possibly due to the administration of the ACIC tool and components of counselling services for family planning and HIV/AIDS services.

Maternal Decision-Making Input and Health-Seeking Behaviors Between Pregnancy and the Child's Second Birthday: A Cross-Sectional Study in Nepal.

OBJECTIVES: Maternal health-seeking behaviors are critical to improving maternal and child health in low-income countries. This study investigates associations between maternal decision-making input and their health-seeking behaviors in the first 1000-day period between pregnancy and a child's second birthday in Nepal. METHODS: We used data from a cross-sectional survey conducted in 2018 in 16 districts of Nepal. Among the 3648 households surveyed, 1910 mothers of a child 0 to 24 months with complete data were included for analyses. Logistic regression was used to examine associations between decision-making input and the utilization of antenatal, delivery and postnatal care services, and attendance at health mothers' group (HMG) meetings. We also used negative binomial regression to assess the relationship between her decision-making input and participation in growth monitoring and promotion (GMP) in the 6 months prior to the survey. For each relationship examined, we adjusted for clustering, as well as potentially confounding factors at individual and household levels. RESULTS: After adjusting for confounders, maternal decision-making input had a small but positive and significant association with receiving at least 4 antenatal care visits (OR = 1.09, 95% CI 1.02, 1.17), attendance at GMP in the 6 months prior to the survey (IRR = 1.02, 95% CI 1.00, 1.04), and HMG attendance (OR = 1.10, 95% CI 1.03, 1.17), but not with receiving at least 3 postnatal care visits or delivering in a health institution. CONCLUSIONS FOR PRACTICE: Our findings indicated that empowering women and mothers in household decision-making might warrant greater attention when developing future policies and programs in Nepal.

Inflammation throughout pregnancy and fetal growth restriction in rural Nepal.

Maternal systemic inflammation during pregnancy may restrict embryo-fetal growth, but the extent of this effect remains poorly established in undernourished populations. In a cohort of 653 maternal-newborn dyads participating in a multi-armed, micronutrient supplementation trial in southern Nepal, we investigated associations between maternal inflammation, assessed by serum α1-acid glycoprotein and C-reactive protein, in the first and third trimesters of pregnancy, and newborn weight, length and head and chest circumferences. Median (IQR) maternal concentrations in α1-acid glycoprotein and C-reactive protein in the first and third trimesters were 0.65 (0.53-0.76) and 0.40 (0.33-0.50) g/l, and 0.56 (0.25-1.54) and 1.07 (0.43-2.32) mg/l, respectively. α1-acid glycoprotein was inversely associated with birth size: weight, length, head circumference and chest circumference were lower by 116 g (P = 2.3 × 10-6), and 0.45 (P = 3.1 × 10-5), 0.18 (P = 0.0191) and 0.48 (P = 1.7 × 10-7) cm, respectively, per 50% increase in α1-acid glycoprotein averaged across both trimesters. Adjustment for maternal age, parity, gestational age, nutritional and socio-economic status and daily micronutrient supplementation failed to alter any association. Serum C-reactive protein concentration was largely unassociated with newborn size. In rural Nepal, birth size was inversely associated with low-grade, chronic inflammation during pregnancy as indicated by serum α1-acid glycoprotein.

Psychological resilience and the gene regulatory impact of posttraumatic stress in Nepali child soldiers.

Adverse social conditions in early life have been linked to increased expression of proinflammatory genes and reduced expression of antiviral genes in circulating immune cells-the conserved transcriptional response to adversity (CTRA). However, it remains unclear whether such effects are specific to the Western, educated, industrialized, rich, and democratic (WEIRD) cultural environments in which previous research has been conducted. To assess the roles of early adversity and individual psychological resilience in immune system gene regulation within a non-WEIRD population, we evaluated CTRA gene-expression profiles in 254 former child soldiers and matched noncombatant civilians 5 y after the People's War in Nepal. CTRA gene expression was up-regulated in former child soldiers. These effects were linked to the degree of experienced trauma and associated distress-that is, posttraumatic stress disorder (PTSD) severity-more than to child soldier status per se. Self-perceived psychological resilience was associated with marked buffering of CTRA activation such that PTSD-affected former child soldiers with high levels of personal resilience showed molecular profiles comparable to those of PTSD-free civilians. These results suggest that CTRA responses to early life adversity are not restricted to WEIRD cultural contexts and they underscore the key role of resilience in determining the molecular impact of adverse environments.

Translational opportunities for broad-spectrum natural phytochemicals and targeted agent combinations in breast cancer.

Breast cancer (BC) prevention and therapy in the context of life-style risk factors and biological drivers is a major focus of developmental therapeutics in oncology. Obesity, alcohol, chronic estrogen signaling and smoking have distinct BC precipitating and facilitating effects that may act alone or in combination. A spectrum of signaling events including enhanced oxidative stress and changes in estrogen-receptor (ER)-dependent and -independent signaling drive the progression of BC. Breast tumors modulate ERα/ERß ratio, upregulate proliferative pathways driven by ERα and HER2 with a parallel loss and/or downregulation of tumor suppressors such as TP53 and PTEN which together impact the efficacy of therapeutic strategies and frequently lead to emergence of drug resistance. Natural phytochemicals modulate oxidative stress, leptin, integrin, HER2, MAPK, ERK, Wnt/ß-catenin and NFκB signaling along with regulating ERα and ERß, thereby presenting unique opportunities for both primary and combinatorial interventions in BC. In this regard, this article focuses on critical analyses of the evidence from multiple studies on the efficacy of natural phytochemicals in BC. In addition, areas in which the combinations of such effective natural phytochemicals with approved and/or developing anticancer agents can be translationally beneficial are discussed to derive evidence-based inference for addressing challenges in BC control and therapy.

Psychotropic drugs in Nepal: perceptions on use and supply chain management.

BACKGROUND: Psychotropic drugs play an important role in the treatment of mental, neurological and substance use disorders. Despite the advancement of the use of psycho-pharmaceuticals in the developed countries, the psychotropic drug production and supply chain management in low- and middle- income countries are still poorly developed. This study aims to explore the perceptions of stakeholders involved in all stages of the psychotropic drug supply chain about the need, quality, availability and effectiveness of psychotropic drugs, as well as barriers to their supply chain management. The study was conducted among 65 respondents from the Kathmandu, Chitwan and Pyuthan districts, grouped into four categories: producers, promoters and distributors (N = 22), policy makers and government actors (N = 8), service providers (N = 21) and service users/family members (N = 14). RESULTS: The respondents reported that psychotropic drugs, despite having side effects, are 1) needed, 2) available in major regional centers and 3) are effective for treating mental health problems. The stigma associated with mental illness, however, forces patients and family members to hide their use of psychotropic drugs. The study found that the process of psychotropic drug supply chain management is similar to other general drugs, with the exceptions of strict pre-approval process, quantity restriction (for production and import), and mandatory record keeping. Despite these regulatory provisions, respondents believed that the misuse of psychotropic drugs is widespread and companies are providing incentives to prescribers and retailers to retain their brand in the market. CONCLUSIONS: The production and supply chain management of psychotropic drugs is influenced by the vested interests of pharmaceutical companies, prescribers and pharmacists. In the context of the government of Nepal's policy of integrating mental health into primary health care and increased consumption of psychotropic drugs in Nepal, there is a need for massive education and awareness as well as strict monitoring and supervision to avoid the misuse of psychotropic drugs.