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Mali national policy recommends that women take iron and folic acid supplements (IFA) from the time of the first antenatal care (ANC) visit, throughout pregnancy and during the first 3 months after delivery. In 2020, the World Health Organization (WHO) updated their ANC guidelines to recommend the United Nations International Multiple Micronutrient Antenatal Preparation (UNIMMAP) formulation of multiple micronutrient supplements (MMS) in the context of rigorous research, including implementation research. In Bamako, Mali, a codesign process was used to tailor antenatal care MMS packaging and counselling materials aimed at optimizing delivery and uptake of and adherence to MMS. This paper presents the codesign process along with the results of a post-intervention qualitative assessment to evaluate the behaviour change intervention. At the conclusion of the intervention, we conducted semistructured qualitative interviews with 24 women who had received the intervention and six pharmacy managers from the six health centres participating in the study. We conducted two focus groups with midwives who had delivered the intervention and two group discussions with family members of women who had received the intervention. Respondent perspectives reveal an easy experience transitioning from previously used IFA. Women and providers concur that the intervention counselling materials and visual aids were instrumental in influencing the perceived benefit and uptake of MMS. Family members play an influential role in pregnant women's decision-making regarding MMS uptake. MMS and the associated implementation strategies developed through the codesign process were found to be a highly acceptable intervention., (© 2024 The Author(s). Maternal & Child Nutrition published by John Wiley & Sons Ltd.)

Left ventricular hypertrophy (LVH) is often used as an indicator to assess hypertension-mediated organ damage (HMOD), alongside hypertensive retinopathy (HR) and nephropathy. Assessment of HMOD is crucial when making decisions about treatment optimization. Despite longstanding debate over its reliability to detect LVH, it is common practice to perform an electrocardiogram (ECG) instead of directly assessing left ventricular mass with echocardiography. In this study, the presence of LVH was evaluated using both ECG and echocardiography among consecutive patients suspected of therapy-resistant hypertension or secondary hypertension in the outpatient clinic of the Department of Internal Medicine at the Diakonessen Hospital, Utrecht, the Netherlands, between July 15, 2017, and July 31, 2020. The primary endpoints were the specificity and sensitivity of ECG as a diagnostic tool for LVH, with echocardiography serving as the reference method. Among the 329 participants, we identified 70 individuals (21.3%) with true LVH based on echocardiography. The ECG displayed a sensitivity of 47.9% and a specificity of 75.3%. Moreover, the area under the receiver operating characteristics curve was 0.604. In conclusion, ECG demonstrates limited value in identifying LVH. Considering the importance of accurately assessing HMOD for treatment optimization of hypertension, the role of ECG as a diagnostic tool for LVH is, therefore, questionable. Instead, we recommend employing standard echocardiography as a more reliable diagnostic., (© 2024 The Author(s). The Journal of Clinical Hypertension published by Wiley Periodicals LLC.)

Undernutrition and a lack of learning opportunities can jeopardize long-term growth and development among infants in low- and middle-income countries. We conducted a 6-month 2 × 2 cluster-randomized trial to assess the effects of multiple micronutrient-fortified beverages and responsive caregiving interventions among infants 6-18 months in 72 community sectors in southwest Guatemala. We administered baseline and endline assessments of childhood development (Bayley Scales of Infant and Toddler Development) and socioemotional development (Brief Infant Toddler Socio-Emotional Assessment) and measured ferritin and hemoglobin on a subsample. The trial was analyzed using linear mixed models. At the baseline, the mean age (SD) was 13.0 (4.6) months, including 49% males, 32% who were stunted, 55% who were anemic, and 58% who were iron deficient. At the endline ( n = 328/386, 85% retention), there was no synergistic effect on the fortified beverage and responsive caregiving intervention. Compared to the non-fortified beverage group, socioemotional development improved in the fortified beverage group. There were no intervention effects on other measures of child development, hemoglobin, or ferritin. In a setting with high rates of anemia and iron deficiency, a multiple micronutrient-fortified beverage improved infants' socioemotional development.

Background: Anemia is a global public health problem that undermines childhood development. India provides government-sponsored integrated nutrition/child development preschools., Objectives: This double-masked, cluster-randomized controlled trial examines whether point-of-use multiple micronutrient powder (MNP) compared with placebo fortification of preschool meals impacts child development and whether effects vary by preschool quality (primary outcome) and biomarkers of anemia and micronutrients (secondary outcomes). We also measured growth and morbidity., Methods: We randomly assigned 22 preschools in rural India to receive MNP/placebo fortification. We administered baseline and endline blood sampling and measures of childhood development (Mullen Scales of Early Learning, inhibitory control, social-emotional), anthropometry, and morbidity to preschoolers (aged 29-49 mo). Preschools added MNP/placebo to meals 6 d/wk for 8 mo. We conducted linear mixed-effects regression models accounting for preschool clustering and repeated measures. We evaluated child development, examining effects in high- compared with low-quality preschools using the Early Childhood Environment Rating Scale-Revised and the Home Observation for the Measurement of the Environment Inventory, modified for preschools., Results: At baseline, mean age ± SD was 36.6 ± 5.7 mo, with 47.8% anemic, 41.9% stunted, and 20.0% wasted. Baseline expressive/receptive language scores were higher in high-quality compared with low-quality preschools (P = 0.02 and P = 0.03, respectively). At endline (91% retention, n = 293/321), we found MNP compared with placebo effects in expressive language (Cohen's standardized effect d = 0.4), inhibitory control (d = 0.2), and social-emotional (d = 0.3) in low-quality, not high-quality, preschools. MNP had significantly greater reduction of anemia and iron deficiency compared with placebo (37% compared with 13.5% and 41% compared with 1.2%, respectively). There were no effects on growth or morbidity., Conclusions: Providing multiple micronutrient-fortified meals in government-sponsored preschools is feasible; reduced anemia and iron deficiency; and, in low-quality preschools, increased preschoolers' expressive language and inhibitory control and reduced developmental disparities. Improving overall preschool quality by incorporating multiple components of nurturing care (responsive care, learning, and nutrition) may be necessary to enhance preschoolers' development. This trial was registered at clinicaltrials.gov as NCT01660958., (© The Author(s) 2021. Published by Oxford University Press on behalf of the American Society for Nutrition.)

Background: Growth failure in sub-Saharan Africa leads to a high prevalence of child stunting starting in infancy, and is attributed to dietary inadequacy, poor hygiene, and morbidity., Objectives: To evaluate the impact of a program in Malawi providing a lipid-based nutrient supplement to infants from 6-23 months of age, accompanied by a social and behavior change communication intervention to optimize caregiver feeding and handwashing practices., Methods: This impact evaluation was a quasi-experimental, longitudinal study with 1 program and 1 comparison district. Infants were enrolled at 6-7 months of age. Anthropometry, child morbidity, and caregiver feeding and handwashing practices were assessed at enrollment and at 6, 12, and 18 month follow-ups (ages 6, 12, 18, and 24 months, respectively). Changes in the length-for-age z-score (LAZ), weight-for-length z-score (WLZ), and midupper arm circumference (MUAC) were compared using mixed-effects models. Program impacts on child stunting (LAZ < -2), wasting (WLZ < -2), morbidity, and feeding and handwashing practices were estimated using difference-in-differences., Results: We enrolled 367 infants across the program (n = 176) and comparison (n = 191) districts. The combined prevalences of stunting and wasting at enrollment were 42.1% and 1.4%, respectively, and did not differ by district. At enrollment, the prevalence of severe stunting (LAZ < -3) was higher in the program (15.5%) versus comparison (7.6%) district (P = 0.02), with corresponding lower LAZ scores (-1.9 vs. -1.7, respectively; P = 0.12). Growth velocities favored program children, such that LAZ, WLZ, and MUAC measurements increased by +0.12/y (P = 0.06), +0.12/y (P = 0.04), and +0.24 cm/y (P < 0.001), respectively, leading to comparable LAZ distributions across districts by 24 months of age. Program exposure was associated with 19.8 percentage point (pp) and 13.8 pp reductions in the prevalences of malaria (P = 0.001) and fever (P = 0.02), respectively, at the 18-month follow-up. Improvements of 20 pp (P < 0.01) in minimum dietary diversity and minimum acceptable diet were seen in the program versus comparison district at 18 months of follow-up., Conclusions: The program improved child growth patterns, with benefits to health and diet apparent after 18 months of exposure. This trial was registered at clinicaltrials.gov as NCT02985359., (© The Author(s) 2021. Published by Oxford University Press on behalf of the American Society for Nutrition.)

Rapid weight gain increases risks of obesity and associated co-morbidities. The objective was to reduce the rate of body mass index (BMI) growth (BMI z score), relative to control. Secondary outcomes were toddler-mother physical activity, mealtime interactions and fruit/vegetable intake. The randomized three-arm, eight-session, 4-month trial, conducted 2009-2013, included two intervention arms (responsive parenting and maternal lifestyle) and an attention control (home safety). Baseline and 6- and 12-month follow-up evaluations included weight and length/height, ankle accelerometry, video-recorded mealtime interactions (Emotional Availability Scales) and 24-h diet recalls (Healthy Eating Index-2015 [HEI-2015]). Analyses used linear mixed-effects models with repeated measures comparing intervention versus control changes in BMI z score. We recruited 277 racially mixed (70% African American) toddler-mother dyads (mean ages 20.1 months and 27.3 years) from US WIC and primary care clinics and randomized them into intervention versus control; 31% toddlers and 73% mothers were overweight/obese. At follow-up, changes in the rate of toddler BMI z score and maternal BMI were non-significant. Maternal lifestyle group toddlers and mothers spent 24.43 and 11.01 more minutes in physical activity (95% confidence interval [CI]: 2.55, 46.32, and 95% CI: 1.48, 20.54, respectively). Fruit intake increased in both intervention groups. Hostile mealtime interactions increased in the maternal lifestyle group, and in supplementary analyses, mealtime interactions were significantly higher in the responsive parenting group than in the maternal lifestyles group, suggesting that toddler dietary interventions include responsive parenting. Intervention effects were stronger among older versus younger toddlers. Despite no impact on weight gain, additional research should examine integrated two-generation responsive parenting and maternal lifestyle interventions among toddler-mother dyads., (© 2020 The Authors. Maternal & Child Nutrition published by John Wiley & Sons Ltd.)

Background: The prevalence of stunting in central rural Malawi is ∼50%, which prompted a multipronged nutrition program in 1 district from 2014 to 2016. The program distributed a daily, fortified, small-quantity lipid-based nutritional supplement, providing 110 kcal and 2.6 g of protein to children aged 6-23 mo, and behavior change messages around optimal infant and young child feeding (IYCF) and water, sanitation, and hygiene., Objectives: Our objective was to perform an impact evaluation of the program using a neighboring district as comparison., Methods: Using a quasi-experimental study design, with cross-sectional baseline (January-March, 2014; n = 2404) and endline (January-March, 2017; n = 2453) surveys, we evaluated the program's impact using a neighboring district as comparison. Impact on stunting was estimated using propensity score weighted difference-in-differences regression analyses to account for baseline differences between districts., Results: No differences in mean length-for-age z-score or prevalence of stunting were found at endline. However, mean weight, weight-for-length z-score, and mid-upper arm circumference were higher at endline by 150 g, 0.22, and 0.19 cm, respectively, in the program compared with the comparison district (all P < 0.05). Weekly reports of high fever and malaria were also lower by 6.4 and 4.7 percentage points, respectively, in the program compared with the comparison district (both P < 0.05). There was no impact on anemia. Children's dietary diversity score improved by 0.17, and caregivers' infant and young child feeding and hand-washing practices improved by 8-11% in the program compared with the comparison district (all P < 0.05)., Conclusions: An impact evaluation of a comprehensive nutrition program in rural Malawi demonstrated benefit for child ponderal growth and health, improved maternal IYCF and hand-washing practices, but a reduction in stunting prevalence was not observed., (Copyright © The Author(s) on behalf of the American Society for Nutrition 2020.)

We evaluated the association between maternal anxiety score and diet quality over time among mothers and toddlers in low-income families. Longitudinal data were collected from 267 mother-toddler dyads in an obesity prevention trial. Participants were recruited from the Special Supplemental Nutrition Program for Women, Infants and Children and paediatric clinics between 2007 and 2010. Dyads were assessed at study enrolment (Time 1), 6-month (Time 2), and 12-month follow-up (Time 3). On the basis of a 1-day 24-hr dietary recall, we estimated maternal and toddler diet quality using the Healthy Eating Index 2015. Anxiety, a time-varying variable, was assessed via the State-Trait Anxiety Inventory. Associations between maternal anxiety score and maternal and toddler diet quality over time were assessed in adjusted mixed models. Maternal and toddler diet quality were positively correlated (r = .48, p < .001). Higher maternal anxiety scores were related to lower toddler Healthy Eating Index scores (b = -0.51, 95% confidence interval, CI [-0.87, -0.15]) with no significant variation over time. The relation between maternal diet quality and anxiety score varied over time (b = 0.28, p = .03, for time-anxiety interaction). Higher maternal anxiety scores were associated with lower maternal diet quality at Time 1 (b = -0.71, 95% CI [-1.09, 0.34]) and at Time 2 (b = -0.51, 95% CI [-0.97, -0.05]), but not at Time 3 (b = -0.14, 95% CI [-0.54, 0.26]). Findings suggest that mothers and toddlers exhibited similar low-quality dietary patterns and that lower diet quality was associated with higher maternal anxiety scores. Approaches to enhance diet quality may consider incorporating anxiety-reducing strategies into maternal and toddler care and feeding behaviour guidelines., (© 2020 The Authors. Maternal & Child Nutrition published by John Wiley & Sons Ltd.)

Background: Nutrient-level intakes from home-prepared complementary foods are rarely estimated among infants and young children in low-income settings. The major constraints are related to lack of standard recipes and ingredients and portion sizes., Objectives: This article describes the feasibility, applicability, and validity of a post hoc qualitative methodology to estimate nutrient intakes in children using 24-h dietary recall., Methods: Semistructured, interviewer-administered caregiver 24-h diet recalls were conducted to assess food intake among children participating in a randomized trial of complementary food supplementation at ages 6, 9, 12, 15, 18, and 24 mo in rural Bangladesh. At the end of the diet data collection, focus group discussions with mothers ( n  = 6) and cooking activities ( n  = 5) were conducted to obtain standard recipes (and ingredients) and portion sizes for reported foods given at different ages. Nutrient intakes were calculated for children in the control group ( n  = 1438), and convergent validity of the data was tested by examining the association of energy and protein intakes with child age and socioeconomic status (SES)., Results: Focus group discussions generated standardized recipes for 21 commonly consumed mixed dishes being fed to children. These recipes were cooked, and portion sizes of standardized measures used in 24-h recalls were quantified in grams. For discrete foods, we quantified women's perceptions of "small," "medium," and "large" in grams. Across all ages, food groups consumed consisted mostly of staples, with the most common being rice, potatoes, and biscuits. Using portion size data and recipe ingredients, the 24-h dietary data, and Bangladeshi food composition tables, we successfully estimated nutrient intakes in children. Convergent validity analysis showed that energy and protein intakes were strongly associated with age and SES (both P  < 0.001)., Conclusions: We demonstrated the use of a validated, qualitative methodology for estimating nutrient intakes in young children from complementary foods in undernourished contexts. This trial was registered at clinicaltrials.gov as NCT01562379., (Copyright © The Author(s) on behalf of the American Society for Nutrition 2020.)

One in four children younger than age five in Guatemala experiences anaemia (haemoglobin <11.0 g/dl). This study characterized the factors and micronutrient deficiencies associated with anaemia in a baseline cross-sectional sample of 182 Guatemalan infants/toddlers and 207 preschoolers, using generalized linear mixed models. Associations between anaemia and maternal, child and household variables, and biomarkers (soluble transferrin receptor, ferritin, zinc, folate, vitamin B12, C-reactive protein, and α1-acid glycoprotein) were explored. Rates of anaemia were 56% among infants/toddlers and 12.1% among preschoolers. In children with anaemia, rates of iron deficiency (low ferritin based on inflammation status, and/or high soluble transferrin receptor, ≥1.97 mg/L) and zinc deficiency (serum zinc <65 μg/dl) were 81.1% and 53.7%, respectively. Folate deficiency (either plasma folate <3 ng/ml or erythrocyte folate <100 ng/ml) was 3.3%. Vitamin B12 deficiency (plasma vitamin B12 <148 pmol/L) was 7.5%. For infants and toddlers (<24 months), the odds ratio of anaemia was lower when higher number of adults lived in the household (OR = 0.69; 95% CI [0.53, 0.90]), and higher when children were zinc deficient (OR = 3.40; 95% CI [1.54, 7.47]). For preschoolers (36-60 months), the odds ratio of anaemia was lower for every additional month of age (OR = 0.90; 95% CI [0.81, 1.00]). Findings suggest that micronutrient deficiencies coexist in Guatemalan rural children, and zinc deficiency is associated with anaemia in children <24 months, highlighting the need of continued multidisciplinary interventions with multiple micronutrients. Further research examining how household composition, feeding practices, and accessibility to micronutrient supplements and to animal source foods is needed to incorporate strategies to improve the nutritional status of Guatemalan children., (© 2019 The Authors. Maternal & Child Nutrition published by John Wiley & Sons, Ltd.)

Background: Global attention to the study of nutrition program implementation has been inadequate yet is critical for effective delivery and impact at scale., Objectives: The objective of this mixed-methods process evaluation study was to measure the recruitment, fidelity, and reach of a large-scale, community-based nutrition program in Malawi., Methods: The nutrition program delivered a small-quantity lipid-based nutrient supplement (SQ-LNS) and social and behavior change communication (SBCC) to improve infant and young child feeding (IYCF) and water, sanitation, and hygiene (WASH) practices in households with children aged 6-23 mo. Program monitoring and evaluation data were used to measure program recruitment, reach, and fidelity. Structured direct observations and knowledge questionnaires with program volunteers measured quality aspects of program fidelity. The number of times activities were done correctly was used to tabulate proportions used to represent program functioning., Results: Half (49.5%) of eligible children redeemed program benefits by 8 mo of age during the first 4 y of program implementation. Implementation of training activities for SBCC cadres exceeded program targets (100.6%), but the completion of certain modules (breastfeeding and complementary feeding) was lower (22.9% and 18.6%, respectively). Knowledge of IYCF, WASH, and SQ-LNS messages by volunteers was >85% for most messages, except ability to list the 6 food groups (35.7%). Structured direct observations of SQ-LNS distributions indicated high fidelity to program design, whereas those of household-level counseling sessions revealed lack of age-appropriate messaging. Program reach showed participation in monthly distribution sessions of 81.0%, group counseling of 93.3%, and individual-level counseling of 36.9%., Conclusions: This community-based nutrition program was implemented with high fidelity and quality, with specific interventions requiring further attention. The documentation of implementation contributes to our understanding about how program impacts were achieved., (Copyright © The Author(s) 2019.)

Objective: Excess gestational weight gain (GWG) in obese women is linked to adverse maternal outcomes and is particularly pervasive among African Americans, who have the highest obesity rates in the USA. A better understanding of culturally relevant attitudes and perceptions of GWG is needed to develop targeted interventions to prevent excess GWG among this group., Design: Using the constructs of Social Cognitive Theory, we explored attitudes and perceptions surrounding diet and exercise among low-income obese African-American pregnant women in Baltimore. We conducted twenty-one semi-structured in-depth interviews with pregnant adult women., Setting: Participants were recruited from a referral clinic for obese pregnant women at a large urban hospital in Baltimore, MD, USA., Participants: Twenty-one low-income African-American adult females in the first two trimesters of pregnancy with BMI &gt; 30·0 kg/m2., Results: Lack of knowledge was not the main obstacle to healthy behaviours during pregnancy. Rather, food cravings and fatigue, an unhealthy physical food environment, limited self-efficacy for controlling excessive GWG, and a lack of adequate emotional and informational support impacted women's agency. While digital technology was discussed as a vehicle to promote maintenance of a healthy weight in pregnancy, further research is needed to test how it can be used to empower women to engage in healthy behaviours during pregnancy., Conclusion: Interventions to prevent excess GWG among African-American pregnant women should harness support from partners and family and must go beyond sharing of clinical knowledge to also include strategies that improve the food environment, diet quality and self-efficacy.

Objective: To examine the association between household food insecurity and dietary diversity in the past 24h (dietary diversity score (DDS, range: 0-9); minimum dietary diversity (MDD, consumption of three or more food groups); consumption of nine separate food groups) among pregnant and lactating women in rural Malawi., Design: Cross-sectional study., Setting: Two rural districts in Central Malawi., Subjects: Pregnant (n 589) and lactating (n 641) women., Results: Of surveyed pregnant and lactating women, 66·7 and 68·6 %, respectively, experienced moderate or severe food insecurity and only 32·4 and 28·1 %, respectively, met MDD. Compared with food-secure pregnant women, those who reported severe food insecurity had a 0·36 lower DDS (P&lt;0·05) and more than threefold higher risk (OR; 95 % CI) of not consuming meat/fish (3·19; CI 1·68, 6·03). The risk of not consuming eggs (3·77; 1·04, 13·7) was higher among moderately food-insecure pregnant women. Compared with food-secure lactating women, those who reported mild, moderate and severe food insecurity showed a 0·36, 0·44 and 0·62 lower DDS, respectively (all P&lt;0·05). The risk of not achieving MDD was higher among moderately (1·95; 1·06, 3·59) and severely (2·82; 1·53, 5·22) food-insecure lactating women. The risk of not consuming meat/fish and eggs increased in a dose-response manner among lactating women experiencing mild (1·75; 1·01, 3·03 and 2·81; 1·09, 7·25), moderate (2·66; 1·47, 4·82 and 3·75; 1·40, 10·0) and severe (5·33; 2·63, 10·8 and 3·47; 1·19, 10·1) food insecurity., Conclusions: Addressing food insecurity during and after pregnancy needs to be considered when designing nutrition programmes aiming to increase dietary diversity in rural Malawi.

Background: Inadequate complementary feeding is common in low- and middle-income countries, contributing to growth deficits. Complementary food supplements (CFSs) aim to fill dietary gaps, but few CFS studies have measured nutrient intake. In a community-based, randomized CFS trial in Bangladesh, we previously reported poor dietary diversity in 6-18-mo-old participants., Objective: We investigated, in a secondary analysis in the same trial, micronutrient intake adequacy in supplemented compared with control-arm children., Methods: At age 6 mo, children were assigned to 1 y of child-feeding counseling for mothers (control) or counseling plus 1 of 4 CFS formulations. Mothers were administered quantitative past 24-h diet questionnaires for their children at ages 6, 9, 12, 15, and 18 mo. Nutrient intakes were estimated with local recipes and food composition tables assuming average age-specific breastmilk intake. Adequacy was evaluated relative to estimated average requirements or adequate intakes. Multivariate analysis of variance and generalized estimating equation (GEE) regression models estimated the effect of each CFS on nutrient adequacy. GEE models tested dietary predictors of nutrient adequacy in the control arm., Results: A total of 25,964 dietary modules across 5 interviews were completed. Nutrient adequacy from home foods combined with assumed breastmilk intake was low. Only 5 of 16 micronutrients were adequately consumed by >60% of children at 18 mo of age. Daily CFSs did not affect energy-adjusted micronutrient intake from home foods at any follow-up age (P > 0.05). CFSs increased the mean adequacy ratio for all micronutrients (P < 0.001 at all ages), to ≥1 for 14 of 16 micronutrients at 18 mo. Dietary diversity predicted adequate iron, zinc and calcium intake at 15 mo in unsupplemented controls., Conclusions: Home foods did not meet the estimated micronutrient needs of 9-18-mo-old children in rural Bangladesh. Daily supplementation with fortified complementary foods filled many micronutrient intake gaps and did not displace home foods. Previously, CFSs were shown to also improve linear growth and reduce stunting in this cohort. Findings support the need for CFSs in similar settings to promote nutritional well being and growth. This trial was registered at clinicaltrials.gov as NCT01562379.

The double burden of malnutrition, defined by the coexistence of undernutrition and overweight, is well documented in low- and middle-income countries. However, the mechanisms by which employment may be related to maternal and child weight status in low- and middle-income countries are not well understood. We conducted in-depth interviews among 20 mothers who participated in Project MIEL, a contemporary trial which evaluated the effects of an integrated micronutrient supplement and parenting intervention in rural Guatemala. We utilized semi-structured interviews to explore the pathways by which maternal employment might influence bodyweight. Interviews were structured to explore the factors that mothers considered when deciding whether or not to participate in the labor force and how mothers perceived the influence of employment on determinants of their own bodyweight and that of their children. Themes were used to develop a conceptual framework. Mothers described four pathways through which employment could lead to changes in weight status: changes in food purchasing; improved household well-being; changes in time allocation; and psychological effects. Mothers described purchasing increased quantities and more varied types of food, as well as the purchase of energy-dense foods. Less time to devote to food preparation resulted in mothers preparing quicker meals and relying on substitute childcare. Mothers also expressed feelings of worry and neglect in relation to being employed, and perceived that these feelings would affect weight. A better understanding of these mechanisms is important for developing policies and programs to support women in the workplace and also reducing maternal and child overweight in Guatemala., (© 2017 John Wiley & Sons Ltd.)

Objective: To determine whether living in a food swamp (≥4 corner stores within 0·40 km (0·25 miles) of home) or a food desert (generally, no supermarket or access to healthy foods) is associated with consumption of snacks/desserts or fruits/vegetables, and if neighbourhood-level socio-economic status (SES) confounds relationships., Design: Cross-sectional. Assessments included diet (Youth/Adolescent FFQ, skewed dietary variables normalized) and measured height/weight (BMI-for-age percentiles/Z-scores calculated). A geographic information system geocoded home addresses and mapped food deserts/food swamps. Associations examined using multiple linear regression (MLR) models adjusting for age and BMI-for-age Z-score., Setting: Baltimore City, MD, USA., Subjects: Early adolescent girls (6th/7th grade, n 634; mean age 12·1 years; 90·7 % African American; 52·4 % overweight/obese), recruited from twenty-two urban, low-income schools., Results: Girls' consumption of fruit, vegetables and snacks/desserts: 1·2, 1·7 and 3·4 servings/d, respectively. Girls' food environment: 10·4 % food desert only, 19·1 % food swamp only, 16·1 % both food desert/swamp and 54·4 % neither food desert/swamp. Average median neighbourhood-level household income: $US 35 298. In MLR models, girls living in both food deserts/swamps consumed additional servings of snacks/desserts v. girls living in neither (β=0·13, P=0·029; 3·8 v. 3·2 servings/d). Specifically, girls living in food swamps consumed more snacks/desserts than girls who did not (β=0·16, P=0·003; 3·7 v. 3·1 servings/d), with no confounding effect of neighbourhood-level SES. No associations were identified with food deserts or consumption of fruits/vegetables., Conclusions: Early adolescent girls living in food swamps consumed more snacks/desserts than girls not living in food swamps. Dietary interventions should consider the built environment/food access when addressing adolescent dietary behaviours.

Postpartum, low-income mothers are at risk for mental health symptoms and obesity, and disordered eating attitudes may be associated with both mental health and obesity in this vulnerable population. The study objective is to determine whether higher levels of mental health symptoms are associated with increased odds of emotional and restrained eating attitudes in this sample of Special Supplemental Nutrition Program for Women, Infants and Children (WIC) participants. Data on 711 mothers of infants <13 months from a statewide sample of Maryland WIC participants were collected via telephone survey. Maternal mental health symptoms were measured on continuous scales for depression (PRIME-MD), stress (Perceived Stress Scale) and anxiety (Spielberger State-Trait Anxiety Inventory). Emotional and restrained eating attitudes were measured with questions adapted from the Dutch Eating Behavior Questionnaire. Multivariate logistic regression analysis was used. Obesity [body mass index (BMI) ≥ 30] was explored as a moderating variable. Mothers reporting higher levels of depression symptoms [odds ratio (OR) = 3.93, 95%CI: 2.71-5.69], anxiety symptoms (OR = 1.96, 95%CI: 1.47-2.65), stress symptoms (OR = 2.09, 95%CI: 1.67-2.61) and high overall mental health symptomatology (OR = 3.51, 95%CI: 2.43-5.3) had increased odds of emotional eating attitudes. There were significant associations between symptoms of depression (OR = 1.59, 95% CI: 1.12-2.25) and increased odds of restrained eating attitudes. Obesity did not moderate the association. Mothers with mental health symptoms are at risk for disordered eating attitudes, which may increase risk of poor diet. These findings underscore the need for greater focus on addressing maternal mental health status and eating attitudes in the postpartum period., (© 2016 John Wiley & Sons Ltd.)

Background: Complementary food supplements (CFSs) can enhance growth where stunting is common, but substitution for the usual diet may reduce observed benefits., Objective: We aimed to characterize dietary diversity from home foods in a CFS efficacy trial and determine whether supplementation reduced breastfeeding frequency or displaced home foods., Design: In a cluster-randomized controlled trial in rural Bangladesh, children (n = 5499) received, for 1 y starting at age 6 mo, periodic child feeding counseling for mothers (control) or counseling plus 1 of 4 CFSs fed as a daily snack. Breastfeeding status and past 24-h diet were assessed at enrollment and every 3 mo thereafter until 18 mo of age. A 7-food group dietary diversity score (DDS) was calculated from home foods only, and a DDS ≥4 constituted minimum dietary diversity (MDD)., Results: Most children (97%) were breastfed through 18 mo of age, and 24-h breastfeeding frequency did not differ by supplementation group. Child dietary diversity was low; only 51% of children met the MDD by 18 mo. Rice, potatoes, and biscuits (cookies) were the most frequently consumed foods, whereas the legumes, dairy, eggs, and vitamin A-rich fruit and vegetable food groups were each consumed by <50% of children. The odds of meeting the MDD through the consumption of home foods were equal or greater in the supplemented groups compared with the control group at all ages. High socioeconomic status and any maternal education were associated with increased odds of MDD at age 18 mo, whereas child sex and household food security were not associated with MDD., Conclusions: In a setting where daily complementary food supplementation improved linear growth, there was no evidence that supplementation displaced breastfeeding or home foods, and the supplementation may have improved dietary diversity. Pathways by which supplementation with fortified foods may enhance dietary diversity, such as an improved appetite and increased body size, need elucidation. This trial was registered at clinicaltrials.gov as NCT01562379.

Background: Childhood obesity, one of the greatest challenges to public health, disproportionately affects low-income urban minority populations. Fruits and vegetables (FV) are nutrient dense foods that may be inversely associated with excessive weight gain. We aimed to identify the individual characteristic, psychosocial, and household factors influencing FV and fiber consumption in low-income African-American (AA) youth in Baltimore, MD., Methods: Cross-sectional analysis of data collected from 285 low-income AA caregiver-youth (age range: 10-14 y) dyads participating in the baseline evaluation of the B'More Healthy Communities for Kids obesity prevention trial. The Kid's Block FFQ was used to estimate daily intakes of FV (including 100 % fruit juice) and dietary fiber. Questionnaires were used to assess household socio-demographics, caregiver and youth food purchasing and preparation behavior, and youth psychosocial information. Ordered logit regression analyses were conducted to examine psychosocial and food-related behavior associated with FV and dietary fiber intake (quartile of intake) controlling for youth age, sex, BMI percentile, total calorie intake and household income., Results: On average, youth consumed 1.5 ± 1.1 (M ± SD) servings of fruit, 1.8 ± 1.7 serving of vegetables, and 15.3 ± 10.9 g of fiber/day. There were no differences by gender, age or household income. Greater youth's healthy eating intentions and self-efficacy scores were associated with greater odds ratio for higher intake of FV and fiber (Intention: ORfruit 1.22; 95 % CI: 1.06-1.41, ORvegetable 1.31; 1.15-1.51 and ORfiber 1.46; 1.23-1.74, Self-efficacy: ORfruit 1.07; 1.03-1.12, ORvegetable 1.04; 1.01-1.09, ORfiber 1.10; 1.04-1.16). Youth receiving free/low-cost breakfast were more than twice as likely to have higher fiber intake than those who did not receive free breakfast (OR 2.7; 1.10; 6.9). In addition, youth shopping more frequently at supermarkets were more likely to have greater vegetable and fiber intake (OR 1.26; 1.06-1.50; OR 1.28; 1.03-1.58, respectively). Also, youth with parents who shopped more frequently at fast-food stores had 7 % lower odds for higher vegetable intake (95 % CI: 0.88-0.99)., Conclusion: In this study, both, youth and household factors were associated with youth FV and fiber intake, underscoring the need for a multi-level approach to increasing youths' diet quality. These results will inform and shape an effective intervention program for improving youth dietary intakes.

Objective: In India, national databases indicate anaemia prevalence of 80 % among 6-35-month-old children and 58 % among 36-59-month-old children. The present study aimed to characterise anaemia and the associated factors among infants and pre-schoolers living in rural India., Design: Multivariate logistic regression analysis of data collected prior to an intervention trial. Fe-deficiency with anaemia (IDA), Fe deficiency with no anaemia (IDNA) and anaemia without Fe deficiency were defined. Serum ferritin, soluble transferrin receptor (sTfR) and sTfR/log ferritin index were used to indicate Fe status., Setting: Twenty-six villages of Nalgonda district, Telangana, India. Data were collected in community sites. Participants Four hundred and seventy-six infants (aged 6-12 months), 316 pre-schoolers (aged 29-56 months) and their mothers., Results: Prevalence of anaemia among infants and pre-schoolers was 66·4 and 47·8 %, prevalence of IDA was 52·2 and 42·1 %, prevalence of IDNA was 22·2 and 29·8 %, prevalence of anaemia without Fe deficiency was 14·2 and 5·7 %. Among infants, anaemia was positively associated with maternal anaemia (OR=3·31; 95 % CI 2·10, 5·23; P<0·001), and sTfR/log ferritin index (OR=2·21; 95 % CI 1·39, 3·54; P=0·001). Among pre-schoolers, anaemia was positively associated with maternal anaemia (OR=3·77; 95 % CI 1·94, 7·30; P<0·001), sTfR/log ferritin index (OR=5·29; 95 % CI 2·67, 10·50; P<0·001), high C-reactive protein (OR=4·39; 95 % CI 1·91, 10·06, P<0·001) and young age (29-35 months: OR=1·92; 05 % CI 1·18, 3·13, P=0·009)., Conclusions: Anaemia prevalence continues to be high among infants and pre-schoolers in rural India. Based on sTfR/ferritin index, Fe deficiency is a major factor associated with anaemia. Anaemia is also associated with inflammation among pre-schoolers and with maternal anaemia among infants and pre-schoolers, illustrating the importance of understanding the aetiology of anaemia in designing effective control strategies.

Poor nutrition (substandard diet quantity and/or quality resulting in under- or overnutrition) and the lack of early learning opportunities contribute to the loss of developmental potential and life-long health and economic disparities among millions of children aged <5 y. Single-sector interventions representing either early child development (ECD) or nutrition have been linked to positive child development and/or nutritional status, and recommendations currently advocate for the development and testing of integrated interventions. We reviewed the theoretical and practical benefits and challenges of implementing integrated nutrition and ECD interventions along with the evidence for best practice and benefit-cost and concluded that the strong theoretical rationale for integration is more nuanced than the questions that the published empirical evidence have addressed. For example, further research is needed to 1) answer questions related to how integrated messaging influences caregiver characteristics such as well-being, knowledge, and behavior and how these influence early child nutrition and development outcomes; 2) understand population and nutritional contexts in which integrated interventions are beneficial; and 3) explore how varying implementation processes influence the efficacy, uptake, and cost-benefit of integrated nutrition and ECD interventions., (© 2016 American Society for Nutrition.)

The study's objective was to examine the relation between maternal mental health and infant dietary intake. A cross-sectional, population-based telephone survey was employed within a statewide sample of Maryland Special Supplemental Nutrition Program for Women, Infants and Children participants. A 24-h diet recall was performed using the United States Department of Agriculture Automated Multiple-Pass Method. Analyses presented were based on 689 mother-infant pairs. Overall, 36.5% of mothers reported introducing solids to their infants early (<4 months of age), and 40% reported adding cereal to their infant's bottle. Among 0-6-month-old infants, higher infant energy intake was associated with symptoms of maternal stress [β=0.02; confidence interval (CI): 0.01, 0.04], depression (β=0.04; CI: 0.01, 0.06) and overall maternal psychological distress (β=0.02; CI: 0.003, 0.03). With early introduction of solids in the model, the significant associations between infant energy intake and maternal stress and maternal psychological distress became marginal (P's=0.06-0.10). The association between infant energy intake and maternal depression remained significant (β=0.03; CI: 0.01, 0.06). Among 4-6-month-old infants, intakes of breads and cereals were higher among mothers who reported more symptoms of stress (β=0.12; CI: 0.04, 0.23), depression (β=0.19; CI: 0.03, 0.34), anxiety (β=0.15; CI: 0.02, 0.27) and overall psychological distress (β=0.04; CI: 0.01, 0.07). Among 7-12-month-old infants, dietary intake was not related to mental health symptoms. Findings suggest poorer infant feeding practices and higher infant dietary intake during the first 6 months of age in the context of maternal mental health symptoms. Further research is needed to evaluate these effects on child dietary habits and growth patterns over time., (© 2012 Blackwell Publishing Ltd.)

This paper describes the development and validation of a 27-item caregiver-reported questionnaire on toddler feeding. The development of the Toddler Feeding Behavior Questionnaire was based on a theory of interactive feeding that incorporates caregivers' responses to concerns about their children's dietary intake, appetite, size, and behaviors rather than relying exclusively on caregiver actions. Content validity included review by an expert panel (n = 7) and testing in a pilot sample (n = 105) of low-income mothers of toddlers. Construct validity and reliability were assessed among a second sample of low-income mothers of predominately African-American (70%) toddlers aged 12-32 mo (n = 297) participating in the baseline evaluation of a toddler overweight prevention study. Internal consistency (Cronbach's α: 0.64-0.87) and test-retest (0.57-0.88) reliability were acceptable for most constructs. Exploratory and confirmatory factor analyses revealed 5 theoretically derived constructs of feeding: responsive, forceful/pressuring, restrictive, indulgent, and uninvolved (root mean square error of approximation = 0.047, comparative fit index = 0.90, standardized root mean square residual = 0.06). Statistically significant (P < 0.05) convergent validity results further validated the scale, confirming established relations between feeding behaviors, toddler overweight status, perceived toddler fussiness, and maternal mental health. The Toddler Feeding Behavior Questionnaire adds to the field by providing a brief instrument that can be administered in 5 min to examine how caregiver-reported feeding behaviors relate to toddler health and behavior.

Objective: To investigate the relationship between maternal depression and child growth in developing countries through a systematic literature review and meta-analysis., Methods: Six databases were searched for studies from developing countries on maternal depression and child growth published up until 2010. Standard meta-analytical methods were followed and pooled odds ratios (ORs) for underweight and stunting in the children of depressed mothers were calculated using random effects models for all studies and for subsets of studies that met strict criteria on study design, exposure to maternal depression and outcome variables. The population attributable risk (PAR) was estimated for selected studies., Findings: Seventeen studies including a total of 13,923 mother and child pairs from 11 countries met inclusion criteria. The children of mothers with depression or depressive symptoms were more likely to be underweight (OR: 1.5; 95% confidence interval, CI: 1.2-1.8) or stunted (OR: 1.4; 95% CI: 1.2-1.7). Subanalysis of three longitudinal studies showed a stronger effect: the OR for underweight was 2.2 (95% CI: 1.5-3.2) and for stunting, 2.0 (95% CI: 1.0-3.9). The PAR for selected studies indicated that if the infant population were entirely unexposed to maternal depressive symptoms 23% to 29% fewer children would be underweight or stunted., Conclusion: Maternal depression was associated with early childhood underweight and stunting. Rigorous prospective studies are needed to identify mechanisms and causes. Early identification, treatment and prevention of maternal depression may help reduce child stunting and underweight in developing countries.

Child overweight/obesity continues to be a serious public health problem in high-income countries. The current review had 3 goals: 1) to summarize the associations between responsive feeding and child weight status in high-income countries; 2) to describe existing responsive feeding measures; and 3) to generate suggestions for future research. Articles were obtained from PubMed and PsycInfo using specified search criteria. The majority (24/31) of articles reported significant associations between nonresponsive feeding and child weight-for-height Z-score, BMI Z-score, overweight/obesity, or adiposity. Most studies identified were conducted exclusively in the United States (n = 22), were cross-sectional (n = 25), and used self-report feeding questionnaires (n = 28). A recent trend exists toward conducting research among younger children (i.e. infants and toddlers) and low-income and/or minority populations. Although current evidence suggests that nonresponsive feeding is associated with child BMI or overweight/obesity, more research is needed to understand causality, the reliability and validity between and within existing feeding measures, and to test the efficacy of responsive feeding interventions in the prevention and treatment of child overweight/obesity in high-income countries.

Objective: This study examined the association of maternal depression with the emotional and behavioral problems and adaptive skills of four- to ten-year-old children as rated by their mothers, fathers, and teachers., Methods: Eighty-four mothers had major depressive disorder, and 49 did not. They were predominantly African American or Latino and lived in low-income, urban communities. Mothers, fathers, and teachers reported on children's emotional and behavioral problems and adaptive functioning. Parenting behavior and family stress were examined as potential mediators, and generalized estimating equations were used to test mediation and to account for discrepancies in reports by different raters., Results: According to the combined reports, children of mothers with depression had significantly poorer adaptive skills than children of sociodemographically similar mothers without depression; according to the reports of mothers and fathers, these children also had more emotional and behavioral problems. The quality of mothers' parenting mediated these associations, but measured family stressors did not., Conclusions: This study contributes to the scientific literature by demonstrating the effects of raters and testing mediators of maternal depression in low-income African-American and Latino families. It demonstrated that mothers, fathers, and teachers observed worse functioning among children of mothers with depression than without depression, although reporters' perspectives varied somewhat. The impact of maternal depression over and above that of poverty suggests the importance of developing and funding services to address the needs of affected families.

Chronic disease is related to poor diet quality. The Healthy Eating Index (HEI) was developed to assess diet quality. The Youth HEI (YHEI) is an adaptation of the HEI for use with children and adolescents. The objectives were to compare HEI and YHEI scores among adolescents at risk for chronic disease and to compare associations between the scores and health indicators. This cross-sectional study included 2 low-income, urban African American adolescent samples (Challenge, n = 196; Three Generation, n = 121). HEI and YHEI scores were calculated from a FFQ and compared with BMI, body composition, and micronutrient, energy, and dietary intakes. YHEI scores were lower than HEI scores across both adolescent samples (Challenge, 48.94 +/- 9.31 vs. 62.83 +/- 11.75; Three Generation, 47.08 +/- 9.65 vs. 59.93 +/- 11.27; P < 0.001). Females (64.47 +/- 11.70) had higher HEI scores than males (61.15 +/- 11.61) (P < 0.05), but there was no gender difference in YHEI scores. HEI and YHEI scores were associated with higher micronutrient and total energy intakes (r = 0.19-0.76; P < 0.05). Higher percent body/abdominal fat was associated with lower HEI scores (r = -0.17 to -0.19; P < 0.05) but not with YHEI scores. BMI was not associated with either HEI or YHEI scores. In conclusion, many adolescents were consuming diets that placed them at risk for developing chronic disease. Although both the HEI and YHEI are useful in assessing diet quality, the HEI is inversely associated with body composition, a predictor of chronic disease, and accounts for gender differences in the Dietary Guidelines, whereas the YHEI discounts nutrient-poor, energy-dense foods.

Parenting, including nonresponsive feeding styles, has been related to under- or overweight among young children. The relationship between maternal mental health and feeding styles has not been examined. We hypothesized that mothers who report more symptoms of stress, depression, or anxiety report less responsive (e.g. more controlling, indulgent, and uninvolved) feeding styles than mothers who report fewer symptoms of stress, depression, or anxiety. Our analyses included 702 mother-infant pairs from a statewide sample of Special Supplemental Nutrition Program for Women, Infants, and Children mothers. We assessed maternal mental health and feeding styles by a telephone survey. After adjusting for potential confounding variables, maternal stress symptomatology was significantly associated with forceful (beta = 0.03; 95% CI = 0.02, 0.05) and uninvolved (OR = 1.4; 95% CI = 1.1, 1.7) feeding style scores, maternal depression symptomatology was significantly associated with forceful (beta = 0.03; 95% CI = 0.004, 0.05), indulgent (beta = 0.03; 95% CI = 0.004, 0.06), and uninvolved (OR = 1.5; 95% CI = 1.001, 2.2) feeding styles scores, and maternal anxiety symptomatology was significantly related to restrictive (beta = 0.11; 95% CI = 0.01, 0.21), forceful (beta = 0.04; 95% CI = 0.02, 0.06), and uninvolved (OR = 1.4; 95% CI = 1.01, 1.9) feeding style scores. Among mothers who perceived their infant as temperamentally fussy, there was a significant positive relationship between restrictive feeding styles scores and 3 indices of maternal mental health (stress, beta = 0.18; 95% CI = 0.07, 0.28; depression, beta = 0.21; 95% CI = 0.04, 0.38; and cumulative mental health symptomatology, beta = 0.29; 95% CI = 0.10, 0.48). Mothers who report stress, depression, or anxiety symptoms are at risk for nonresponsive feeding styles. These findings provide support for broadening the focus of existing child nutrition programs to include strategies that recognize how issues of maternal mental health can affect feeding styles.

The objective of this study was to examine how breastfeeding behaviours, perceptions and experiences vary by race/ethnicity among a low-income sample in the USA. Bilingual interviewers conducted a cross-sectional telephone survey of 767 white, African American or Hispanic mothers who received the Special Supplemental Nutrition Program for Women, Infants, and Children (WIC). Rates of breastfeeding initiation and duration varied by race/ethnicity. Hispanic mothers were more likely to initiate breastfeeding than African American (91% vs. 65%) or white (61%) mothers. Hispanic mothers breastfed longer (mean 5 months) than either African American (mean 3.5 months) or white (mean 3 months) mothers. The most common reason for not breastfeeding was fear of difficulty or pain during breastfeeding (35.6%). Among mothers who did not initiate breastfeeding, African American and white mothers were more likely than Hispanic mothers to report perceptions of breastfeeding difficulty or pain, and Hispanic mothers were more likely than African American and white mothers to report perceptions of infant breast rejection. The most common reason reported for breastfeeding cessation was not having enough milk (23.4%). Hispanic mothers were more likely than African American and white mothers to cite perceptions of milk insufficiency and infant breast refusal than concerns regarding breast discomfort or pain. African American mothers were more likely than white mothers to report cessation to return to work. In conclusion, while breastfeeding initiation rates approach Healthy People 2010 goals, breastfeeding duration remains far below these goals. Race/ethnicity differences in experiences related to breastfeeding cessation suggest that culturally sensitive breastfeeding interventions are necessary.

Two kinds of sodium current (I(Na)) have been separately reported in hair cells of the immature rodent utricle, a vestibular organ. We show that rat utricular hair cells express one or the other current depending on age (between postnatal days 0 and 22, P0-P22), hair cell type (I, II, or immature), and epithelial zone (striola vs. extrastriola). The properties of these two currents, or a mix, can account for descriptions of I(Na) in hair cells from other reports. The patterns of Na channel expression during development suggest a role in establishing the distinct synapses of vestibular hair cells of different type and epithelial zone. All type I hair cells expressed I(Na,1), a TTX-insensitive current with a very negative voltage range of inactivation (midpoint: -94 mV). I(Na,2) was TTX sensitive and had less negative voltage ranges of activation and inactivation (inactivation midpoint: -72 mV). I(Na,1) dominated in the striola at all ages, but current density fell by two-thirds after the first postnatal week. I(Na,2) was expressed by 60% of hair cells in the extrastriola in the first week, then disappeared. In the third week, all type I cells and about half of type II cells had I(Na,1); the remaining cells lacked sodium current. I(Na,1) is probably carried by Na(V)1.5 subunits based on biophysical and pharmacological properties, mRNA expression, and immunoreactivity. Na(V)1.5 was also localized to calyx endings on type I hair cells. Several TTX-sensitive subunits are candidates for I(Na,2).

Type I vestibular hair cells have large K+ currents that, like neuronal M currents, activate negative to resting potential and are modulatable. In rodents, these currents are acquired postnatally. In perforated-patch recordings from rat utricular hair cells, immature hair cells [younger than postnatal day 7 (P7)] had a steady-state K+ conductance (g(-30)) with a half-activation voltage (V1/2) of -30 mV. The size and activation range did not change in maturing type II cells, but, by P16, type I cells had added a K conductance that was on average fourfold larger and activated much more negatively. This conductance may comprise two components: g(-60) (V1/2 of -60 mV) and g(-80) (V1/2 of -80 mV). g(-80) washed out during ruptured patch recordings and was blocked by a protein kinase inhibitor. M currents can include contributions from KCNQ and ether-a-go-go-related (erg) channels. KCNQ and erg channel blockers both affected the K+ currents of type I cells, with KCNQ blockers being more potent at younger than P7 and erg blockers more potent at older than P16. Single-cell reverse transcription-PCR and immunocytochemistry showed expression of KCNQ and erg subunits. We propose that KCNQ channels contribute to g(-30) and g(-60) and erg subunits contribute to g(-80). Type I hair cells are contacted by calyceal afferent endings. Recordings from dissociated calyces and afferent endings revealed large K+ conductances, including a KCNQ conductance. Calyx endings were strongly labeled by KCNQ4 and erg1 antisera. Thus, both hair cells and calyx endings have large M-like K+ conductances with the potential to control the gain of transmission.

The subfamily of G-protein-linked inwardly rectifying potassium channels (GIRKs) is coupled to G-protein receptors throughout the CNS and in the heart. We used mutational analysis to address the role of a specific hydrophobic region of the GIRK1 subunit. Deletion of the GIRK1 C-terminal residues 330-384, as well as the point mutation I331R, resulted in a decrease in channel function when coexpressed with GIRK4 in oocytes and in COS-7 cells. Surface protein expression of GIRK1 I331R coexpressed with GIRK4 was comparable with wild type, indicating that subunits assemble and are correctly localized to the membrane. Subsequent mutation of homologous residues in both the GIRK4 subunit and Kir2.1 (Gbetagamma-independent inward rectifier) also resulted in a decrease in channel function. Intracellular domain associations resulted in the coimmunoprecipitation of the GIRK1 N and C termini and GIRK4 N and C termini. The point mutation I331R in the GIRK1 C terminus or L337R in the GIRK4 C terminus decreased the association between the N and C termini. Mutation of a GIRK1 N-terminal hydrophobic residue, predicted structurally to interact with the C-terminal domain, also resulted in a decrease in channel function and termini association. We hypothesize that the hydrophobic nature of this GIRK1 subunit region is critical for interaction between adjacent termini and is permissive for channel gating. In addition, the homologous mutation in cytoplasmic domains of Kir2.1 (L330R) did not disrupt association, suggesting that the overall structural integrity of this region is critical for inward rectifier function.

Cochlear and type I vestibular hair cells of mammals express negatively activating potassium (K(+)) conductances, called g(K,n) and g(K,L) respectively, which are important in setting the hair cells' resting potentials and input conductances. It has been suggested that the channels underlying both conductances include KCNQ4 subunits from the KCNQ family of K(+) channels. In whole-cell recordings from rat hair cells, we found substantial differences between g(K,n) and g(K,L) in voltage dependence, kinetics, ionic permeability, and stability during whole-cell recording. Relative to g(K,L), g(K,n) had a significantly broader and more negative voltage range of activation and activated with less delay and faster principal time constants over the negative part of the activation range. Deactivation of g(K,n) had an unusual sigmoidal time course, while g(K,L) deactivated with a double-exponential decay. g(K,L), but not g(K,n), had appreciable permeability to Cs(+). Unlike g(K,L), g(K,n)'s properties did not change ("wash out") during the replacement of cytoplasmic solution with pipette solution during ruptured-patch recordings. These differences in the functional expression of g(K,n) and g(K,L) channels suggest that there are substantial differences in their molecular structure as well.

Atrial natriuretic peptide is a potent dilator of aorta and renal and cerebral arteries and inhibits sympathetic tone in the heart in several mammalian species. We examined the possibility that a molecule related to porcine brain natriuretic peptide (pBNP), which acts at the same receptor sites as atrial natriuretic peptide, might provide an alternative source of natriuretic peptide to the cardiovascular system in the rat. An antiserum against pBNP demonstrated profuse immunoreactive innervation of the heart, cerebrovascular tree, and renal arteries. pBNP-like immunoreactive fibers ran in bundles along the surface of the heart, innervating the atria most heavily and penetrating the ventricular myocardium along the coronary arteries. There was greater density of innervation of the right side of the heart compared with the left, particularly in the ventricles, suggesting a parasympathetic origin. The entire cerebrovascular tree was innervated by immunoreactive pBNP fibers, with the densest concentration of immunoreactive fibers along the surface of the internal carotid, middle cerebral, posterior communicating, and anterior cerebral arteries. The proximal renal arteries were not innervated, but as they approached the kidney, they were invested by bundles of immunoreactive pBNP fibers. These axons followed the major branches of the renal artery into the kidney parenchyma, running along the surface of the arterioles up to their entrance into the renal glomeruli. No immunoreactive innervation of the aorta or proximal brachiocephalic, subclavian, or carotid arteries was seen. A substance related to pBNP may serve as a neuromodulator regulating cardiac output as well as blood flow in certain vascular beds.

Brain natriuretic peptide is a recently discovered neuropeptide. We used an antiserum against porcine brain natriuretic peptide to identify a system of immunoreactive innervation of the cerebrovascular tree in the rat. The internal carotid artery and the proximal portions of the middle and anterior cerebral and posterior communicating arteries were the most intensely innervated by immunoreactive fibers. The density of innervation decreased distally along the anterior, middle, and posterior cerebral arteries and the basilar and vertebral arteries. Brain natriuretic peptide and the related atrial natriuretic peptide are known to cause dilatation of cerebral arteries. Our findings suggest that brain natriuretic peptide may serve as a vasodilatory neuromodulator in the cerebral circulation.