Zinc Supplementation Initiated Prior to or During Pregnancy Modestly Impacted Maternal Status and High Prevalence of Hypozincemia in Pregnancy and Lactation: The Women First Preconception Maternal Nutrition Trial.

BACKGROUND: Data regarding effects of small-quantity-lipid-based nutrient supplements (SQ-LNS) on maternal serum zinc concentrations (SZC) in pregnancy and lactation are limited. OBJECTIVES: The objectives of this study were to evaluate the effect of preconception compared with prenatal zinc supplementation (compared with control) on maternal SZC and hypozincemia during pregnancy and early lactation in women in low-resource settings, and assess associations with birth anthropometry. METHODS: From ∼100 women/arm at each of 3 sites (Guatemala, India, and Pakistan) of the Women First Preconception Maternal Nutrition trial, we compared SZC at 12- and 34-wk gestation (n = 651 and 838, respectively) and 3-mo postpartum (n = 742) in women randomly assigned to daily SQ-LNS containing 15 mg zinc from ≥3 mo before conception (preconception, arm 1), from ∼12 wk gestation through delivery (early pregnancy, arm 2) or not at all (control, arm 3). Birth anthropometry was examined for newborns with ultrasound-determined gestational age. Statistical analyses were performed separately for each time point. RESULTS: At 12-wk gestation and 3-mo postpartum, no statistical differences in mean SZC were observed among arms. At 34-wk, mean SZC for arms 1 and 2 were significantly higher than for arm 3 (50.3, 50.8, 47.8 µg/dL, respectively; P = 0.005). Results were not impacted by correction for inflammation or albumin concentrations. Prevalence of hypozincemia at 12-wk (<56 µg/dL) was 23% in Guatemala, 26% in India, and 65% in Pakistan; at 34 wk (<50 µg/dL), 36% in Guatemala, 48% in India, and 74% in Pakistan; and at 3-mo postpartum (<66 µg/dL) 79% in Guatemala, 91% in India, and 92% in Pakistan. Maternal hypozincemia at 34-wk was associated with lower birth length-for-age Z-scores (all sites P = 0.013, Pakistan P = 0.008) and weight-for-age Z-scores (all sites P = 0.017, Pakistan P = 0.022). CONCLUSIONS: Despite daily zinc supplementation for ≥7 mo, high rates of maternal hypozincemia were observed. The association of hypozincemia with impaired fetal growth suggests widespread zinc deficiency in these settings. This trial is registered at clinicaltrials.gov as #NCT01883193.

The Cost and Cost-Effectiveness of an Integrated Wasting Prevention and Screening Intervention Package in Burkina Faso and Mali.

BACKGROUND: Little is known about costs and cost effectiveness of interventions that integrate wasting prevention into screening for child wasting. OBJECTIVES: This study's objective was to estimate the cost and cost-effectiveness of an intervention that integrated behavior change communication (BCC) and small-quantity lipid-based nutrient supplements (SQ-LNS) into platforms for wasting screening in Burkina Faso (a facility-based platform, where BCC was enhanced compared with standard care) and Mali (a community-based platform, with standard BCC). METHODS: Activity-based costing was used to estimate the cost per child-contact for the intervention and the comparison group, which did not receive the intervention. Costs were ascertained from accounting records, interviews, surveys, and observations. The number of child-contacts was calculated using population size estimates and average attendance rates for each service. Costs per disability-adjusted life year (DALY) averted were estimated using a Markov model populated with data from the parent trials on impact of wasting incidence and treatment coverage. RESULTS: In the intervention group in Burkina Faso, the cost per child-contact of facility-based screening was $0.85 of enhanced BCC was $4.28, and of SQ-LNS was $8.86. In Mali, the cost per child-contact of community-based screening was $0.57, standard BCC was $0.72, and SQ-LNS was $4.14. Although no SQ-LNS costs were incurred in the comparison groups (hence lower total costs), costs per child-contact for screening and BCC were higher because coverage of these services was lower. The intervention package cost $1073 per DALY averted in Burkina Faso and $747 in Mali. CONCLUSIONS: Integration of wasting prevention into screening for child wasting led to higher total costs but lower unit costs than standard screening due to increased coverage. Greater cost-effectiveness could be achieved if BCC were strengthened and led to improved caregiver health and nutrition practices and if screening triggered appropriate use of services and higher treatment coverage.

Nutrition supplementation plus standard of care versus standard of care alone or standard of care plus unconditional cash transfer in the prevention of chronic malnutrition in Southern Angola: study protocol for the MuCCUA study, a cluster randomized controlled trial.

BACKGROUND: Chronic malnutrition is a condition associated with negative impacts on physical and cognitive development. It is multi-causal and can start very early in life, already in utero, thus it is especially challenging to find appropriate interventions to tackle it. The government of Angola is implementing a standard of care program with potential to prevent it, and the provision of cash transfers and the supplementation with small quantity lipid-based nutrients (SQ-LNS) are also promising interventions. We aimed to evaluate the impact of the standard of care program alone and of the standard of care plus a cash transfer intervention in the lineal growth of children less than 2 years old and compare it to the effectiveness of a nutrition supplementation plus standard of care program in Southern Angola. METHODS/DESIGN: The three-arm parallel cluster randomised controlled trial is set in four communes of Huila and Cunene provinces. Clusters are villages or neighbourhoods with a population around 1075 people. A total of twelve clusters were selected per arm and forty pregnant women are expected to be recruited in each cluster. Pregnant women receive the standard of care alone, or the standard of care plus unconditional cash transfer or plus nutritional supplementation during the first 1000 days, from pregnancy to the child reaching 24 months. The primary outcome is the prevalence of stunting measured as height-for-age Z-score (HAZ) < -2 in children below 2 years. Impact will be assessed at 3, 6, 12, 18 and 24 months of children's age. Secondary outcomes include mortality, morbidity, caring, hygiene and nutrition behaviours and practices, and women and children's dietary diversity. Quantitative data are also collected on women's empowerment, household food security, expenditure and relevant clinical and social events at baseline, endline and intermediate time points. DISCUSSION: The results will provide valuable information on the impact of the standard of care intervention alone as well as combined with an unconditional cash transfer intervention compared to a nutrition supplementation plus standard of care intervention, carried out during the first 1000 days, in the children´s growth up to 2 years and related outcomes in Southern Angola. TRIAL REGISTRATION: Clinical Trials NCT05571280. Registered 7 October 2022.

Perinatal intervention strategies providing food with micronutrients to pregnant and breastfeeding women in low- and middle-income countries: A scoping review.

In resource-constrained settings, pregnant and breastfeeding women and girls (PBW/G) are particularly vulnerable to undernutrition. Micronutrient-fortified balanced energy protein (BEP) supplementation may be provided to boost maternal nutritional status and improve birth and infant outcomes. We conducted a scoping review of the published literature to determine the impact of BEP and other related nutrition interventions that provided fortified food or cash along with a minimum of 3 micronutrients on maternal, birth, and infant/child outcomes in low- and middle-income countries. We conducted a PubMed search using pre-defined keywords and controlled vocabulary search terms. All titles and abstracts were reviewed for eligibility by two independent reviewers, and data were extracted according to outcome type. We identified 149 eligible research articles that reported on a total of 21 trials and/or programme evaluations which assessed the health impact of one or more products (fortified lipid-based nutrient supplement [LNS, n = 12], fortified blended flours [n = 5], milk-based beverages [n = 2], and local food/snacks [n = 3]) that provided 118-750 kcal/day and varying levels of protein and micronutrients. Only one of these programme evaluations assessed the impact of the provision of cash and fortified food. Effects on maternal outcomes such as gestational weight gain and duration of gestation were promising but inconsistent. Birth outcomes were reported in 15 studies, and the effects on birthweight and birth length were generally positive. Seven studies demonstrated sustained benefits on infant and child growth out of the 15 studies that reported at least one of these outcomes, although data were sparse. Additional research is needed to investigate issues of dose, cost-effectiveness, and incorporation into multi-component interventions.

Anthropometric and sociodemographic variables, but not preconception or prenatal maternal nutrition supplementation, predict neurodevelopment in offspring of the 'Women First' trial.

Multiple factors influence infant and child neurodevelopment in low resource settings. In offspring of participants in the preconception maternal nutrition trial, Women First (WF), we examined the impact of providing a preconception (Arm 1) or prenatal (Arm 2) nutrient supplement (compared to controls, Arm 3) on neurodevelopmental outcomes at 24 months; predictors of neurodevelopment scores; and associations of infant anthropometrics with neurodevelopmental scores. Follow-up visits for anthropometry were conducted at 6-, 12-, 18- and 24-month of age. At 24-months, in a randomized subset, the Bayley Scales of Infant Development, 3rd edition (BSID-III), including cognitive, motor and social-emotional subscales, and the Family Care Indicators (FCI) questionnaire, assessing family and home environment, were completed. Multiple covariates (intervention arm, site, maternal sociodemographic characteristics, FCI subscales, birthweight and 6-24 months' change in anthropometry z-scores, (e.g., ΔLAZ6-2 4) were evaluated by linear regression to predict BSID-III outcomes and to assess associations of anthropometric changes with BSID-III scores. The analysis consisted of 1386 infants (n = 441, 486, 459 for Arms 1, 2 and 3, respectively). None of the domain-specific BSID-III subscale scores differed by maternal intervention arm. Four covariates significantly predicted (p ≤ 0.01) all 3 BSID-III subscales: secondary maternal education, ΔLAZ6 - 24, birthweight >2500 g, and FCI play materials. Linear growth was associated with all domains of neurodevelopment. The results underscore the multi-dimensional aspects of child development represented by the nurturing care framework, including prenatal maternal nutrition, post-natal growth, maternal education for responsive caregiving and opportunities for early learning.

LUNCRW: Prediction of potential lncRNA-disease associations based on unbalanced neighborhood constraint random walk.

Accumulating evidence suggests that long non-coding RNAs (lncRNAs) are associated with various complex human diseases. They can serve as disease biomarkers and hold considerable promise for the prevention and treatment of various diseases. The traditional random walk algorithms generally exclude the effect of non-neighboring nodes on random walking. In order to overcome the issue, the neighborhood constraint (NC) approach is proposed in this study for regulating the direction of the random walk by computing the effects of both neighboring nodes and non-neighboring nodes. Then the association matrix is updated by matrix multiplication for minimizing the effect of the false negative data. The heterogeneous lncRNA-disease network is finally analyzed using an unbalanced random walk method for predicting the potential lncRNA-disease associations. The LUNCRW model is therefore developed for predicting potential lncRNA-disease associations. The area under the curve (AUC) values of the LUNCRW model in leave-one-out cross-validation and five-fold cross-validation were 0.951 and 0.9486 ± 0.0011, respectively. Data from published case studies on three diseases, including squamous cell carcinoma, hepatocellular carcinoma, and renal cell carcinoma, confirmed the predictive potential of the LUNCRW model. Altogether, the findings indicated that the performance of the LUNCRW method is superior to that of existing methods in predicting potential lncRNA-disease associations.

IL-17 regulates DC migration to the peribronchial LNs and allergen presentation in experimental allergic asthma.

IL-17 is associated with different phenotypes of asthma, however, it is not fully elucidated how it influences induction and maintenance of asthma and allergy. In order to determine the role of IL-17 in development of allergic asthma, we used IL-17A/F double KO (IL-17A/F KO) and WT mice with or without neutralization of IL-17 in an experimental allergic asthma model and analyzed airway hyperresponsiveness, lung inflammation, T helper cell polarization, and DCs influx and activation. We report that the absence of IL-17 reduced influx of DCs into lungs and lung draining LNs. Compared to WT mice, IL-17A/F KO mice or WT mice after neutralization of IL-17A showed reduced airway hyperresponsiveness, eosinophilia, mucus hypersecretion, and IgE levels. DCs from draining LNs of allergen-challenged IL-17A/F KO mice showed a reduction in expression of migratory and costimulatory molecules CCR7, CCR2, MHC-II, and CD40 compared to WT DCs. Moreover, in vivo stimulation of adoptively transferred antigen-specific cells was attenuated in lung-draining LNs in the absence of IL-17. Thus, we report that IL-17 enhances airway DC activation, migration, and function. Consequently, lack of IL-17 leads to reduced antigen-specific T cell priming and impaired development of experimental allergic asthma.

Growth from Birth Through Six Months for Infants of Mothers in the "Women First" Preconception Maternal Nutrition Trial.

OBJECTIVE: To evaluate whether the fetal linear growth effects of maternal nutrition supplementation would be maintained through 6 months postnatal age. STUDY DESIGN: The Women First trial was a multicountry, individually randomized clinical trial that compared the impact of maternal nutrition supplementation initiated preconception (Arm 1) vs at ∼11 weeks of gestation (Arm 2), vs no supplement (Arm 3); the intervention was discontinued at delivery. Trial sites were in Democratic Republic of Congo, Guatemala, India, and Pakistan. Analysis includes 2421 infants born to 2408 randomized women. Primary outcome was the trajectory of length-for-age z scores (LAZ) by arm, based on assessments at birth and 1, 3, and 6 months. We fitted longitudinal models on growth from birth to 6 months using generalized estimating equations; maternal intervention effects were evaluated, adjusting for site and baseline maternal covariates. RESULTS: Linear growth for Arms 1 and 2 was statistically greater than for Arm 3 in 3 of the 4 countries, with average pairwise mean differences in LAZ of 0.25 (95% CI 0.15-0.35; P < .001) and 0.19 (95% CI 0.09-0.28; P < .001), respectively. Compared with Arm 3, average overall adjusted relative risks (95% CI) for stunting (LAZ <-2) were lower for Arms 1 and 2: 0.76 (0.66-0.87; P < .001) and 0.77 (0.67-0.88; P < .001), respectively. CONCLUSIONS: Improved linear growth in early infancy observed for the 2 intervention arms supports the critical importance of maternal nutrition before conception and in the early phase of gestation. TRIAL REGISTRATION: ClinicalTrials.gov: NCT01883193.

Infant and Toddler Consumption of Sweetened and Unsweetened Lipid Nutrient Supplements After 2-Week Home Repeated Exposures.

BACKGROUND: Small-quantity lipid-based nutrient supplements (SQ-LNS) are designed to address undernutrition during the complementary feeding period. SQ-LNS contains added sugars, but limited research has assessed whether infants' acceptance varies between versions with and without sugars. OBJECTIVES: Our objective was to examine the effects of repeated exposure on children's acceptance of sweetened and unsweetened SQ-LNS. We aimed to understand caregivers' perceptions of children's liking of the 2 SQ-LNS versions and their influences on infant acceptance of SQ-LNS. METHODS: Caregivers (86% non-Hispanic White) and children (7-24 mo), participated in a randomized, 2-week home-exposure study and baseline and post-home exposure assessments. Children were randomized to receive sweetened or unsweetened SQ-LNS versions, mixed with infant oatmeal. At in-person visits, caregivers fed both SQ-LNS versions to children and rated their child's liking for each. Caregivers fed the SQ-LNS version to which their child was randomized until the child refused to eat more. Acceptance was measured as total grams consumed. Mixed-effects linear models tested the change in SQ-LNS consumed between baseline and postexposure by the SQ-LNS version and number of home exposures. Covariates included the amount of SQ-LNS consumed at baseline, child BMI z-score, child age, and breastfeeding experience. RESULTS: Children's acceptance of both SQ-LNS versions increased from baseline to postexposure (ß, 0.71 g; 95% CI: 0.54-0.89 g; P = 0.04), regardless of SQ-LNS version (P = 0.88) or number of home exposures (P = 0.55). Caregivers rated children's liking of unsweetened SQ-LNS higher at baseline (P = 0.02). Children with lower liking ratings at baseline showed the greatest increases in acceptance between baseline and postexposure (P = 0.01). CONCLUSIONS: Children's acceptance of SQ-LNS increased with repeated exposure, whether offered the sweetened or unsweetened version, providing preliminary support that adding sugar to SQ-LNS may not improve acceptance in young children. Children who initially like the supplement less may need repeated experience to learn to accept SQ-LNS. This trial was registered at clinicaltrials.gov as NCT04544332.

Improved first trimester maternal iodine status with preconception supplementation: The Women First Trial.

Maternal iodine (I) status is critical in embryonic and foetal development. We examined the effect of preconception iodine supplementation on maternal iodine status and on birth outcomes. Non-pregnant women in Guatemala, India and Pakistan (n ~ 100 per arm per site) were randomized ≥ 3 months prior to conception to one of three intervention arms: a multimicronutrient-fortified lipid-based nutrient supplement containing 250-µg I per day started immediately after randomization (Arm 1), the same supplement started at ~12 weeks gestation (Arm 2) and no intervention supplement (Arm 3). Urinary I (µg/L) to creatinine (mg/dl) ratios (I/Cr) were determined at 12 weeks for Arm 1 versus Arm 2 (before supplement started) and 34 weeks for all arms. Generalized linear models were used to assess the relationship of I/Cr with arm and with newborn anthropometry. At 12 weeks gestation, adjusted mean I/Cr (µg/g) for all sites combined was significantly higher for Arm 1 versus Arm 2: (203 [95% CI: 189, 217] vs. 163 [95% CI: 152, 175], p < 0.0001). Overall adjusted prevalence of I/Cr < 150 µg/g was also lower in Arm 1 versus Arm 2: 32% (95% CI: 26%, 38%) versus 43% (95% CI: 37%, 49%) (p = 0.0052). At 34 weeks, adjusted mean I/Cr for Arm 1 (235, 95% CI: 220, 252) and Arm 2 (254, 95% CI: 238, 272) did not differ significantly but were significantly higher than Arm 3 (200, 95% CI: 184, 218) (p < 0.0001). Nominally significant positive associations were observed between I/Cr at 12 weeks and birth length and head circumference z-scores (p = 0.028 and p = 0.005, respectively). These findings support the importance of first trimester iodine status and suggest need for preconception supplementation beyond salt iodization alone.

An Integrated Infant and Young Child Feeding and Small-Quantity Lipid-based Nutrient Supplementation Program Is Associated with Improved Gross Motor and Communication Scores of Children 6-18 Months in the Democratic Republic of Congo.

OBJECTIVE: To evaluate the impact of an infant, young child feeding practices-small-quantity lipid nutrient supplements (SQ-LNS) intervention on child development scores in children aged 6-18 months in the Katanga Province, Democratic Republic of Congo (DRC). STUDY DESIGN: We analyzed data of 2595 children from 2 health zones in a quasi-experimental design with preimplementation and postimplementation surveys to evaluate program impact on child development scores. Standard care was received in the comparison health zone and the intervention health zone received standard care plus enhanced infant, young child feeding practices with a monthly supply of 28 SQ-LNS sachets for up to 1 year. Program exposure and communication and motor domains of the Ages and Stages questionnaire were collected to assess changes in child development scores. A quasi-intent-to-treat and adjusted difference-in-difference analyses were used to quantify impact of the enhanced compared with the standard package. RESULTS: In adjusted models contrasting endline with baseline, there was a greater relative increase in proportion of children with normal communication (difference-in-difference, +13.7% [95%CI, 7.9-19.6; P < .001] and gross motor scores, +7.4% [95% CI: 1.3-13.5; P < .001]) in the intervention vs comparison health zones. Further, in separate analyses among children of intervention health zone at endline, each additional SQ-LNS distribution was associated with +0.09 (95% CI, 0.03-0.16) z-score unit increase in gross motor scores (P < .01). CONCLUSIONS: The integrated infant, young child feeding practice-SQ-LNS intervention was positively associated with larger relative improvements in measures of child communication and motor development in the Katanga province of DRC.

Prognostic significance of lymph node yield in patients with synchronous colorectal carcinomas.

BACKGROUND: The National Comprehensive Cancer Network (NCCN) guidelines recommend examination of a minimum of 12 lymph nodes (LNs) for accurate staging of a single case of colorectal cancer. However, the guidelines do not support the examination of LNs in synchronous colorectal carcinoma (SCC). This study aimed to investigate the association between lymph node yield and the prognosis of SCC patients. METHODS: Synchronous colorectal carcinoma patients were selected from the Surveillance, Epidemiology, and End Results (SEER) database over a 10-year interval (2004 to 2013). Systematic dichotomization for optimal cut-off point identification was performed using X-tile. The baseline for the two LNs groups generated was balanced using the propensity score matching (PSM) method. RESULTS: A total of 4616 patients met the inclusion criteria. The cut-off number for lymph node retrieved from a single patient was 15 and 12 for the first- and second-time diagnosis of SCC, respectively. Age, T category, N category, tumor grade, tumor site, tumor size, and radiation sequence were not balanced in the two groups. After adjusting the baseline in the two groups, the same results were observed. Age, T category, N category, tumor site had a partial effect on lymph node yield. There might be some biological characteristics of the tumor that influence lymph node yield. CONCLUSIONS: Retrieval of fewer than 15 LNs at the first time of SCC diagnosis indicates worse SCC prognosis. Because factors such as manner of surgical examination influence SCC prognosis, specimens should be preserved for at least 6 months to enable reevaluation should there be a need. Irb: IRB approval is not required because the SEER data are freely accessible.

Lymph node retrieval after colorectal cancer surgery: a comparative study of the efficacy between the conventional manual method and a new fat dissolution method.

PURPOSE: This study compared the efficacy of two different methods for lymph node (LN) searching after colorectal cancer surgery: the fat dissolution and the conventional manual method. METHODS: For the fat dissolution method, we used a commercially available solution of collagenase and lipase (FD group). The primary endpoint was the number of identified LNs in the FD group compared to an historical control (control group) after adjusting by propensity score matching. RESULTS: Using 37 matched patients from each group, we identified 20.6 ± 7.2 LNs using the fat dissolution method compared to 13.5 ± 5.9 using the conventional method (t test, P < 0.01). Three patients in the FD group received an inappropriate LN examination in terms of number, while the number of the retrieved LNs was < 12 in 12 patients in the control group. The mean diameter of LNs without metastasis was 3.2 ± 1.9 mm in the FD group, and 40% of metastasis cases were found in LNs < 5 mm in diameter. A pathological examination confirmed that using the fat resolution method did not change the morphological or immunochemical staining findings. CONCLUSION: We demonstrated that fat dissolution had a positive impact on the number of retrieved LNs after colorectal cancer surgery without disturbing the microscopic observation.

Effectiveness of a locally produced ready-to-use supplementary food in preventing growth faltering for children under 2 years in Cambodia: a cluster randomised controlled trial.

This cluster randomised controlled trial tested the effectiveness of a locally produced, fish-based, ready-to-use supplementary food (RUSF) to prevent growth faltering (decline in z-scores). Cambodian infants (n= 485), aged 6 to 11 months, were randomised by site to receive the RUSF, Corn-Soy Blend++ (CSB++), micronutrient powders (MNP), or no supplement (control). The intervention was for 6 months. In unadjusted analysis, the control group had statistically significantly decreased weight-for-age z-scores (WAZ; -0.02, 95%CI = -0.03 - -0.01, P= 0.001) and height-for-age z-scores (HAZ; -0.07, 95%CI = -0.09 - -0.05, P < 0.001), and increased mid-upper arm-circumference (MUAC; 0.02cm, 95%CI = 0.01 - 0.04, P = 0.010), but no statistically significant change in weight-for-height z-scores (WHZ). The RUSF group did not differ significantly from the control for WAZ, HAZ or WHZ (in other words, WAZ and HAZ decreased and WHZ did not change), but had increased MUAC in comparison to the control (0.04cm, 95%CI = 0.01 - 0.06, P = 0.008). There were no statistically significant differences between the RUSF group and the CSB++ or MNP groups with respect to WAZ, HAZ, WHZ or MUAC. Interestingly, in adjusted analysis, low consumers of RUSF had increased WAZ, WHZ and MUAC (0.03, 95%CI = 0.01-0.06, P = 0.006; 0.04, 95%CI = 0.01-0.08, P = 0.026; and 0.05cm, 95%CI = 0.02-0.09, P = 0.004, respectively) compared with the control. The novel RUSF, particularly in small quantities, protected against ponderal growth faltering, but the improvements were of limited clinical significance.

Number of retrieved lymph nodes is an independent prognostic factor after total gastrectomy for patients with stage III gastric cancer: propensity score matching analysis of a multi-institution dataset.

BACKGROUND: The prognostic significance of the number of retrieved lymph nodes (RLNs) in gastric cancer remains controversial. Therefore, we designed a multicenter collaborative database to investigate the correlation between the number of RLNs and prognosis of patients with advanced gastric cancer after curative resection. METHODS: We retrospectively analyzed 1103 patients who underwent gastrectomy for stage II/III gastric cancer between 2010 and 2014. Lymph nodes, which were retrieved by surgeons from surgically resected specimens, were validated by pathologists. A target population and the optimal cutoff were determined using receiver operating characteristic (ROC) curve analysis. After propensity score matching of eight variables, including splenectomy and adjuvant chemotherapy, the prognostic significance of RLNs was evaluated. RESULTS: According to ROC curve analysis, the optimum cutoff score for predicting postoperative survival was 40. After matching, the backgrounds of patients in the RLN < 40 and RLN ≥ 40 groups (n = 87 each) became well-balanced. The RLN < 40 group experienced significantly shorter relapse-free and overall survival. The prevalence of peritoneal recurrence was significantly increased in the RLN < 40 group. RLN < 40 was an independent prognostic factor in multivariable analysis, although pathological N status was not. A forest plot revealed that the RLN < 40 group was at greater risk of recurrence in most subgroups. CONCLUSIONS: RLN < 40 was associated with an adverse prognosis of patients with stage III gastric cancer who underwent total gastrectomy.

Development and testing of locally-produced ready-to-use therapeutic and supplementary foods (RUTFs and RUSFs) in Cambodia: lessons learned.

BACKGROUND: Rates of childhood undernutrition are persistently high in Cambodia. Existing ready-to-use supplementary and therapeutic foods (RUSFs and RUTFs) have had limited acceptance and effectiveness. Therefore, our project developed and trialled a locally-produced, multiple micronutrient fortified lipid-based nutrient supplement (LNS) with therapeutic and supplementary versions. This ready-to-use food (RUF) is innovative in that, unlike many RUFs, it contains fish instead of milk. Development began in 2013 and the RUF was finalised in 2015. From 2015 until the present, both the RUTF and the RUSF versions were trialled for acceptability and effectiveness. METHODS: This paper draws on project implementation records and semi-structured interviews to describe the partnership between the Cambodian Ministries of Health and Agriculture, Forestry and Fisheries, UNICEF, the French National Research Institute for Sustainable Development (IRD), universities, and Vissot factory. It discusses the project implementation and lessons learned from the development and trialling process, and insights into positioning nutrition on the health agenda in low and middle-income countries. RESULTS: The lessons learned relate to the importance of project planning, management, and documentation in order to seize opportunities in the research, policy, advocacy, and programming environment while ensuring adequate day-to-day project administration and resourcing. CONCLUSIONS: We conclude that projects such as ours, that collaborate to develop and test novel, locally-produced RUTFs and RUSFs, offer an exciting opportunity to respond to both local programmatic and broader research needs.

Acceptability of locally-produced Ready-to-Use Supplementary Food (RUSF) for children under two years in Cambodia: A cluster randomised trial.

In Cambodia, existing food products for treating or preventing undernutrition have met with limited success. Therefore, in 2014, alternative ready-to-use foods were developed. This trial aimed to assess the acceptability of the novel ready-to-use supplementary food (RUSF) as a snack or mixed with borbor (white rice porridge), compared with corn-soy blend plus plus (CSB++) and borbor fortified with micronutrient powder (MNP). The nonblinded, randomised 4 × 4 crossover trial recruited 95 children aged 9-23 months from communities in peri-urban Phnom Penh. Small quantities (100 g for porridges, 42 g for snack) of each food were offered for three consecutive days at testing sites (homes of health volunteers). Main outcomes were children's consumption, caregivers' assessment of children's preferences, and caregivers' ranking of the foods. Median percentage consumed of the test food servings ranged from 21 to 50% (p = 0.003). The odds of children consuming over 50% were greatest for borbor fortified with MNP versus RUSF snack (unadjusted OR = 6.79, CI = 2.80-16.47, p < 0.001). However, the median energy children received when consuming the RUSF with borbor (57 kcals) or as a snack (48 kcals) was greater than with CSB++ (15 kcals) or borbor fortified with MNP (18 kcals; p < 0.001). Therefore, although children ate less RUSF, it provided approximately three times more kilocalories. Caregivers reported that their children had the highest preference for borbor fortified with MNP. Caregivers themselves ranked the novel RUSF snack highest. Thus, the innovative RUSF was considered sufficiently acceptable to proceed to an effectiveness trial.

Ablation of the Cß2 subunit of PKA in immune cells leads to increased susceptibility to systemic inflammation in mice.

Protein kinase A (PKA) is a holoenzyme composed of a regulatory subunit dimer and two catalytic subunits and regulates numerous cellular functions including immune cell activity. There are two major catalytic subunit genes, PRKACA and PRKACB encoding the catalytic subunits Cα and Cß. The PRKACB gene encodes several splice variants including Cß2, which is enriched in T-, B- and natural killer cells. Cß2 is significantly larger (46 kDa) than any other C splice variant. In this study we characterized mice ablated for the Cß2 protein demonstrating a significantly reduced cAMP-induced catalytic activity of PKA in the spleenocytes, lymphocytes and thymocytes. We also observed a significantly increased number of CD62L-expressing CD4+ and CD8+ T cells in LNs, accompanied by increased susceptibility to systemic inflammation by the Cß2 ablated mice. The latter was reflected in an elevated sensitivity to collagen-induced arthritis (CIA), as well as higher concentration of TNF-α and lower concentration of IL-10 in response to LPS challenges. We suggest a role of Cß2 in regulating innate as well as adaptive immune sensitivity in vivo.

Comparison of an interactive 24-h recall and weighed food record for measuring energy and nutrient intakes from complementary foods among 9-10-month-old Malawian infants consuming lipid-based nutrient supplements.

Fortifying complementary foods with lipid-based nutrient supplements (LNS) may improve energy and nutrient intakes of infants at risk for undernutrition. We aimed to determine the relative validity of an interactive 24-h recall (i-24-HR) for assessing the impact of an LNS intervention on dietary intakes of energy and nutrients among rural Malawian 9-10-month-old infants (n 132) participating in the International Lipid-Based Nutrient Supplements Dose (iLiNS-DOSE) trial. Dietary data were collected for the same day via i-24-HR and weighed food records. Inter-method agreements were estimated overall and by intervention group, using Bland-Altman plots and paired t tests; measurement error models (differential error); and percentage of food omissions and intrusions were estimated. Overall, inter-method differences in mean intakes of energy and most nutrients were not significant. When stratified by group, recalled energy intakes were under-estimated (-368 kJ; P=0·01) in the control but not in the intervention group (-42 kJ; P=0·6). This differential reporting error was related to an over-estimation of recalled LNS (8·1 v. 4·5 g; P30 % eating occasions) omissions were milk/fish/eggs, starchy roots/vegetables and sweetened snacks. Common intrusions were milk/yogurt. Starchy staples and LNS were recalled when consumed (>85 %) (i.e. matched). These results emphasise the importance of considering differential error when interpreting dietary results in LNS trials.

Randomised controlled trial to test the effectiveness of a locally-produced ready-to-use supplementary food (RUSF) in preventing growth faltering and improving micronutrient status for children under two years in Cambodia: a study protocol.

BACKGROUND: Existing ready-to-use supplementary and therapeutic foods (RUSFs and RUTFs) have had limited acceptance and effectiveness in Cambodia. This has hampered the treatment and prevention of child malnutrition. An innovative, locally produced, multiple micronutrient fortified lipid-based nutrient supplement (LNS) has been developed for use as an RUSF. Unlike most RUSFs, which contain milk, this product contains fish as the animal protein. Few RUSFs have been formulated using non-milk animal-source foods and they have not been widely tested. An acceptability trial that was conducted on this novel RUSF in June 2015 demonstrated that children will eat the RUSF and that caregivers will feed it to their children. The current trial aims to evaluate the effectiveness of the RUSF in preventing growth faltering and improving micronutrient status in Cambodian children. METHODS AND ANALYSIS: This trial is a six-month, prospective, cluster randomised, non-blinded controlled trial among infants in peri-urban Phnom Penh. The trial aims to establish the superiority of the novel RUSF, compared to three alternatives (Corn-Soy Blend Plus Plus (CSB++) and Sprinkles micronutrient powders as active comparators, and the unimproved diet as a control). The allocation ratio is 1:1. Healthy children (N = 540) aged six to eleven months will be recruited. Data will be collected at baseline, and monthly thereafter for a period of six months. Participants will be provided with a monthly supply of the food to which their village has been allocated. DISCUSSION: There is an urgent need to develop locally produced and culturally acceptable RUSFs, and to compare these with existing options in terms of their potential for preventing malnutrition, in Cambodia and elsewhere. This trial will contribute much-needed data on the effectiveness of supplementary foods with an animal-source food other than milk, by comparing a novel RUSF based on fish to one that uses milk (CSB++). Moreover, it will deepen the understanding of the impact of multiple micronutrients provided with or without macronutrients, by comparing the novel RUSF and CSB++, which combine macronutrients with multiple micronutrients, to Sprinkles, which contains no macronutrients. In addition, it will augment the body of evidence from Asia. TRIAL REGISTRATION: ClinicalTrials.gov, Identifier: LNS-CAMB-INFANTS-EFF; NCT02257762 .