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Abstract Background and Aims High sodium consumption has been associated with an increased risk of gastric cancer. The mean daily sodium intake in the United States substantially exceeds the national recommended amount. The low sodium‐DASH diet has been shown to decrease the risk of cardiovascular disease in the United States, but its impact on gastric cancer has not been well studied. We therefore aimed to model the impact and cost‐effectiveness of the low sodium‐DASH diet for gastric cancer prevention in the U.S. population. Methods A Markov cohort state‐transition model was developed to simulate the impact of the low sodium‐DASH diet on gastric cancer outcomes for the average 40‐year‐old in the United States compared to no intervention. Primary outcomes of interest were gastric cancer incidence and incremental cost‐effectiveness ratios (ICER). Results Our model found that compared to the no intervention cohort, the risk of gastric cancer decreased by 24.8% for males and 21.2% for females on the low sodium‐DASH diet. 27 cases and 14 cases per 10,000 individuals were prevented for males and females, respectively, in the intervention group. The ICER for the low sodium‐DASH diet strategy was $287,726 for males and $423,878 for females compared to the no intervention strategy. Conclusions Using a Markov model of gastric cancer risk, we found that adherence to a low sodium‐DASH diet could decrease the risk of gastric cancer. This intervention was not cost‐effective due to the high cost of a low sodium‐DASH accordant diet, but significantly improved for high‐risk populations and when the cost of the diet became slightly more affordable.

Background/Aims To determine if patients with a positive intraoperative cholangiogram (IOC) who undergo a subsequent endoscopic retrograde cholangiopancreatography (ERCP) have an increased risk of post-ERCP pancreatitis (PEP) compared to those who undergo ERCP directly for suspected common bile duct stones. Methods A retrospective case-control study was performed from 2010 to 2016. Cases included inpatients with a positive IOC at cholecystectomy who underwent subsequent ERCP. The control group included age-sex matched cohorts who underwent ERCP for choledocholithiasis. Multivariate logistic regression was used to assess the association between PEP and positive IOC, adjusting for matching variables and additional potential confounders. Results Of the 116 patients that met the inclusion criteria, there were 91 women (78%) in each group. Nine patients (7.8%) developed PEP in the IOC group, compared to 3 patients in the control group (2.6%). The use of pancreatic duct stents and rectal indomethacin was similar in both groups. After adjusting for age, sex, total bilirubin levels, and any stent placement, patients with a positive IOC had a significantly increased risk of PEP (odds ratio, 4.79; 95% confidence interval, 1.05–21.89; p

Abstract Background Racial/ethnic differences in mortality have not been well studied for either non‐cardia gastric cancer (NCGC) or cardia gastric cancer (CGC). The aim of this study was to examine the US mortality rates for these cancer subtypes, as well as esophageal adenocarcinoma (EAC) as a comparator. Methods We identified 14 164 individuals who died from NCGC, 5235 from CGC, and 13 982 from EAC in the Surveillance, Epidemiology, and End Results database between 2004 and 2016. Age‐adjusted incidence‐based mortality rates and corresponding annual percent changes (APCs) were calculated. Analyses were stratified by race/ethnicity, age, and stage of disease at diagnosis. Results The mortality rate in NCGC was two‐ to threefold higher in blacks, Hispanics, and Asians/Pacific Islanders (PI) than non‐Hispanic whites, and was significant across all age groups and stages of disease (P

Background and Aim Enteric tube (ET) placement is approached with caution in patients with esophageal varices (EV) due to concern of causing variceal bleeding. Data are limited on rates and predictors of gastrointestinal bleeding (GIB) in these patients. This study aims to assess the rate and predictors of bleeding from EV after ET placement. Methods We performed a retrospective chart review on patients requiring ET access with known EV. Inclusion criteria were age >18 with endoscopically proven EV who required ET placement. Patients who were admitted with, or developed a GIB prior to placement of ET were excluded, as were patients admitted for liver transplantation. Primary outcome was incidence of GIB within 48 h of tube placement. Secondary outcome was a >2 g/dL drop in hemoglobin within 48 h of placement without evidence of bleed. Statistical analysis was performed using Fischer's exact test, Mann–Whitney U test, and univariate logistic regression model. Results A total of 75 patients were included in the analysis. The most common etiology of cirrhosis was alcohol (44%). The most common location of EV was in the lower third of the esophagus (61%). The primary outcome was observed in 11 (14.6%) patients. The secondary outcome was found in eight (10.6%) patients. On univariate analysis, GIB was associated with higher MELD‐Na (P = 0.026) and EV located in the lower third of the esophagus (P = 0.048). Conclusion ET placement in patients with EV is associated with low risk of bleeding. Elevated MELD‐Na and lower EV location conferred a higher risk of bleeding after ET placement.

BackgroundSevere chemotherapy-induced peripheral neuropathy (CIPN) can cause long-term dysfunction of the hands and feet, interfere with activities of daily living, and diminish the quality of life. Monitoring to identify CIPN and adjust treatment before it progressing to a life-altering severity relies on patients self-reporting subjective symptoms to their clinical team. Objective assessment is not a standard component of CIPN monitoring due to the requirement for specially trained health care professionals and equipment. Smartphone apps have the potential to conveniently collect both subjective and objective CIPN data directly from patients, which could improve CIPN monitoring. ObjectiveThe objective of this cross-sectional pilot study was to assess the feasibility of functional CIPN assessment via a smartphone app in patients with cancer that have received neurotoxic chemotherapy. MethodsA total of 26 patients who had completed neurotoxic chemotherapy were enrolled and classified as CIPN cases (n=17) or controls (n=9) based on self-report symptoms. All participants completed CIPN assessments within the NeuroDetect app a single time, including patient-reported surveys (CIPN20 [European Organization for Research and Treatment of Cancer Quality of Life Questionnaire for Chemotherapy-induced Peripheral Neuropathy 20-item scale] and PRO-CTCAE [Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events]) and functional assessments (Gait and Balance and 9-Hole Peg Test). Functional assessment data were decomposed into features. The primary analysis was done to identify features indicative of the difference between CIPN cases and controls using partial least squares analyses. Exploratory analyses were performed to test if any features were associated with specific symptom subtypes or patient-reported survey scores. Patient interviews were also conducted to understand the challenges they experienced with the app. ResultsComparisons between CIPN cases and controls indicate that CIPN cases had shorter step length (P=.007), unique swaying acceleration patterns during a walking task, and shorter hand moving distance in the dominant hands during a manual dexterity task (variable importance in projection scores ≥2). Exploratory analyses showed similar signatures associated with symptoms subtypes, CIPN20, and PRO-CTCAE. The interview results showed that some patients had difficulties due to technical issues, which indicated a need for additional training or oversight during the initial app download. ConclusionsOur results supported the feasibility of remote CIPN assessment via a smartphone app and suggested that functional assessments may indicate CIPN manifestations in the hands and feet. Additional work is needed to determine which functional assessments are most indicative of CIPN and could be used for CIPN monitoring within clinical care.

Background: Increasing evidence points to the esophageal microbiome as an important co-factor in esophageal neoplasia. Esophageal microbiome composition is strongly influenced by the oral microbiome. Salivary microbiome assessment has emerged as a potential non-invasive tool to identify patients at risk for esophageal cancer, but key host and environmental factors that may affect the salivary microbiome have not been well-defined. This study aimed to evaluate the impact of short-term dietary intake on salivary microbiome composition. Methods: Saliva samples were collected from 69 subjects prior to upper endoscopy who completed the Automated Self-Administered 24-Hour (ASA24) Dietary Assessment. Salivary microbiome composition was determined using 16S rRNA amplicon sequencing. Results: There was no significant correlation between alpha diversity and primary measures of short-term dietary intake (total daily calories, fat, fiber, fruit/vegetables, red meat intake, and fasting time). There was no evidence of clustering on beta diversity analyses. Very few taxonomic alterations were found for short-term dietary intake; an increased relative abundance of Neisseria oralis and Lautropia sp. was associated with high fruit and vegetable intake, and an increased relative abundance of a taxon in the family Gemellaceae was associated with increased red meat intake. Conclusions: Short-term dietary intake was associated with only minimal salivary microbiome alterations and does not appear to have a major impact on the potential use of the salivary microbiome as a biomarker for esophageal neoplasia.

Abstract PUF RNA-binding proteins are broadly conserved stem cell regulators. Nematode PUF proteins maintain germline stem cells (GSCs) and, with key partner proteins, repress differentiation mRNAs, including gld-1. Here we report that PUF protein FBF-2 and its partner LST-1 form a ternary complex that represses gld-1 via a pair of adjacent FBF binding elements (FBEs) in its 3′UTR. One LST-1 molecule links two FBF-2 molecules via motifs in the LST-1 intrinsically-disordered region; the gld-1 FBE pair includes a well-established ‘canonical’ FBE and a newly-identified noncanonical FBE. Remarkably, this FBE pair drives both full RNA repression in GSCs and full RNA activation upon differentiation. Discoveries of the LST-1–FBF-2 ternary complex, the gld-1 adjacent FBEs, and their in vivo significance predict an expanded regulatory repertoire of different assemblies of PUF-partner-RNA higher order complexes in nematode GSCs. This also suggests analogous PUF controls may await discovery in other biological contexts and organisms.

ABSTRACTDifferent processing methods could impact on the nutritional and anti-nutritional composition of edible insects. This study involved the analysis of nutrients and anti-nutrients in fresh and processed grasshopper (Ruspolia differens) and winged termites (Nasutitermes spp) in Kenya. Proximate analysis was done using AOAC methods, minerals analysis using AAS and anti-nutrients analysis using UV-VIS and titration. Moisture content reduced significantly to less than 10% on processing, while ash content increased significantly by more than 50% on processing. Processing did not affect the crude fibre content but it led to a 0.2–90% decrease in crude fat. Processing increased significantly the protein content but did not significantly influence mineral levels; however calcium content was reduced considerably. Anti-nutrient levels decreased significantly on processing by 2%–70% with oxalates and phytates having the highest decrease. These results show that oven-drying and defatting methods retained higher nutrient composition in the edible insects.

Abstract Infant and young child feeding (IYCF) practices are influenced by many context‐specific factors related to local food systems as well as social and cultural practices. Understanding these local contextual perspectives is essential for designing effective programs and policies. This paper uses focused ethnographic study methods to examine challenges experienced by mothers related to IYCF in two counties in Kenya, a country with considerable heterogeneity in agriculture, food systems, and cultures. A two‐phase qualitative study was undertaken in each of Kilifi County and West Pokot County, entailing interviews and rating activities with mothers, health workers, and vendors. Interviews were audio‐recorded, transcribed, translated into English, coded, and analysed by topic. Results show low levels of dietary diversity in both counties; in West Pokot, the level of adequate meal frequency is also low. Core foods in young child diets included maize porridge and family foods such as ugali (stiff maize porridge), vegetables, beans, fish, and plantains. Food safety, acceptability, and acquisition ease were the main drivers of food choice. Mothers generally felt that all core foods fed to young children are healthy and safe, but there was more variability regarding child acceptance, acquisition ease, cost, and convenience. Common barriers to feeding nutrient‐dense foods to children included child illness, economic constraints, and limited knowledge of modification strategies, skills, or tools to make the foods suitable for young children. Potential actions to address these barriers include sharing information on child‐appropriate recipes; raising awareness on local, affordable nutrient‐dense foods; and improving WASH practices to reduce illness frequency.

Abstract Background Iron deficiency anemia (IDA) remains high in Kenya despite interventions. Twenty-seven percent of children aged 6 months-14 years are anemic, with low iron intake (7%) among children aged 6–23 months. Standard food interventions involve a corn soy blend (CSB), which is limited in micronutrients, and fortifiers are not accessible locally. Moreover, the use of spirulina as a strategy for mitigating IDA has not been adequately documented. This study compared the impact of a spirulina corn soy blend (SCSB) on IDA among children aged 6–23 months. Methods A total of 240 children with IDA were randomly assigned to study groups at a ratio of 1:1:1 through lotteries, and caregivers and research assistants were blinded to group assignment. Dry-take-home SCSB, CSB and placebo flour (1.7 kg) was given to caregivers to prepare porridges using a flour water ratio of 1:4, producing 600 ml–700 ml of porridge to feed children 200 ml of porridge three times a day for 6 months. Impact was assessed as plasma hematocrit at baseline and after the study. Blood drawing, preparation and analysis were performed in accordance with approved procedures by the EthicsResearchCommittee. Monthly follow-up and data collection on dietary intake, anthropometry, morbidity and infant feeding practices were performed using questionnaires. Relative risk, magnitude of change and log-rank tests were used to compare the impact of the intervention, and significant differences were determined at P

Kenya has registered over 300,000 cases of COVID-19 and is a high-burden tuberculosis country. Tuberculosis diagnosis was significantly disrupted by the pandemic. Access to timely diagnosis, which is key to effective management of tuberculosis and COVID-19, can be expanded and made more efficient through integrated screening. Decentralized testing at community level further increases access, especially for underserved populations, and requires robust systems for data and process management. This study delivered integrated COVID-19 and tuberculosis testing to commercial motorbike (Bodaboda) riders, a population at increased risk of both diseases with limited access to services, in four counties: Nairobi, Kiambu, Machakos and Kajiado. Testing sheds were established where riders congregate, with demand creation carried out by the Bodaboda association. Integrated symptom screening for tuberculosis and COVID-19 was conducted through a digital questionnaire which automatically flagged participants who should be tested for either, or both, diseases. Rapid antigen-detecting tests (Ag-RDTs) for COVID-19 were conducted onsite, while sputum samples were collected and transported to laboratories for tuberculosis diagnosis. End-to-end patient data were captured using digital tools. 5663 participants enrolled in the study, 4946 of whom were tested for COVID-19. Ag-RDT positivity rate was 1% but fluctuated widely across counties in line with broader regional trends. Among a subset tested by PCR, positivity was greater in individuals flagged as high risk by the digital tool (8% compared with 4% overall). Of 355 participants tested for tuberculosis, 7 were positive, with the resulting prevalence rate higher than the national average. Over 40% of riders had elevated blood pressure or abnormal sugar levels. The digital tool successfully captured complete end-to-end data for 95% of all participants. This study revealed high rates of undetected disease among Bodaboda riders and demonstrated that integrated diagnosis can be delivered effectively in communities, with the support of digital tools, to maximize access.

Introduction: Dyslipidemia is a key modifiable cardiovascular risk factor and a major clinical feature in the patients infected with the human immunodeficiency virus (HIV) in the current era of highly active antiretroviral therapy. Peanuts could reduce the risk of cardiovascular diseases as an abundant source of fiber, α-tocopherol, copper, arginine, magnesium, folate, and resveratrol. The present study aimed to evaluate the impact of supplementing peanut and counseling in the form of a healthy diet on the fasting lipid profile of HIV-infected adults. Methods: This randomized crossover clinical trial was conducted on the eligible participants who were randomly assigned to a two-arm study. In treatment I, the participants consumed 80 grams of peanuts plus their regular diet. In treatment II, the participants were provided with nutrition counseling on a healthy diet and consumed 80 grams of peanuts. Each treatment continued for eight weeks with a six-week washout interval. Results: A 3.07% reduction was observed in the total cholesterol of the subjects receiving treatment I, while the reduction rate was 5.39% in treatment II. In addition, a 12.8% decrease was observed in the triglycerides of the subjects receiving treatment 1I, as well as a 17% reduction in treatment II. A significant increase was reported in the high-density lipoprotein cholesterol in treatments I and II, with the rate estimated at 7.38% and 5.1%, respectively. Furthermore, low-density lipoprotein cholesterol decreased by 5.56% in treatment I and 4.32% in treatment II. The estimated 10-year risk of contracting coronary heart disease reduced significantly between the baseline and end of the study (P=0.03). Conclusion: According to the results, regular consumption of peanuts could improve the fasting lipid profile of HIV-infected patients and reduce the risk of coronary heart disease.

Abstract Background Although recent policies have sought to increase the rates of exclusive breastfeeding (EBF) and continued breastfeeding for HIV exposed infants, few programs have considered the multiple social and cultural barriers to the practice. Therefore, to generate evidence for exclusive and continued breastfeeding policies in Kenya, we examined community perspectives on the facilitators and barriers in adherence to EBF for the HIV positive mothers. Methods Qualitative research was conducted in Koibatek, a sub-County in Baringo County Kenya, in August 2014 among 205 respondents. A total of 14 focus group discussions (n = 177), 14 In-depth Interviews and 16 key informant interviews were conducted. Transcribed data was analyzed thematically. NVivo version 10.0 computer qualitative software program was used to manage and facilitate the analysis. Results Facilitators to exclusive breastfeeding were perceived to include counselling at the health facility, desire to have a healthy baby, use of antiretroviral drugs and health benefits associated with breastmilk. Barriers to EBF included poor dissemination of policies, knowledge gap, misinterpretation of EBF, inadequate counselling, attitude of mother and health workers due to fear of vertical HIV transmission, stigma related to misconception and misinformation that EBF is only compulsory for HIV positive mothers, stigma related to HIV and disclosure, social pressure, lack of male involvement, cultural practices and traditions, employment, food insecurity. Conclusions There are multiple facilitators and barriers of optimal breastfeeding that needs a holistic approach to interventions aimed at achieving elimination of mother to child transmission. Extension of infant feeding support in the context of HIV to the community while building on existing interventions such as the Baby Friendly Community Initiative is key to providing confidential support services for the additional needs faced by HIV positive mothers.

Nematode P granules are cytoplasmic RNA–protein biomolecule condensates central to germ cell development. Here the authors show that dimerization of the PGL-1 scaffolding protein is crucial to granule formation and mRNA repression, and that the WAGO-1 Argonaute protein is a cofactor in repressing PGL-1 bound mRNAs.

Abstract Background Although the baby-friendly community initiative (BFCI) has been proposed as a community-level approach to improve infant feeding practices, there is little data on its variation in effectiveness by HIV status. We conducted a study to determine the effectiveness of BFCI in changing knowledge and attitudes towards exclusive breastfeeding (EBF) and increasing the rates among HIV negative and HIV positive women in rural Kenya. Methods A community-based cluster-randomized controlled trial was implemented from April 2015 to December 2016 among 901 women enrolled across 13 clusters. The intervention groups received a minimum of 12 personalized home-based counselling sessions on infant feeding by trained community health volunteers from their first or second trimester of pregnancy until 6 months postpartum. Other interventions included education sessions at maternal child clinics, mother-to-mother support group meetings and bi-monthly baby-friendly gatherings targeting influencers. The control group received standard health education at the facility and during monthly routine home visits by community health volunteers not trained on BFCI. Primary outcome measures were the rates of EBF at week 1, months 2, 4 and 6 postpartum. Secondary outcomes included knowledge and attitudes regarding breastfeeding for HIV-exposed infants. Statistical methods included analysis of covariance and logistic regression. Results At 6 months, EBF rates among HIV negative mothers were significantly higher in the BFCI intervention arm compared to the control arm (81.7% versus 42.2% p = 0.001). HIV positive mothers in the intervention arm had higher EBF rates at 6 months than the control but the difference was not statistically significant (81.8% versus 58.4%; p = 0.504). In HIV negative group, there was greater knowledge regarding EBF for HIV-exposed infants in the intervention arm than in the control (92.1% versus 60.7% p = 0.001). Among HIV positive mothers, such knowledge was high among both the intervention and control groups (96% versus 100%, p > 0.1). HIV negative and positive mothers in the intervention arm had more favourable attitudes regarding EBF for HIV-exposed infants than the control (84.5% versus 62.1%, p = 0.001) and (94.6% versus 53.8% to p = 0.001) respectively. Conclusions BFCI interventions can complement facility-based interventions to improve exclusive and continued breastfeeding knowledge, attitudes, and behaviours among HIV negative and positive women.

Insect species richness and abundance has declined rapidly over the last few decades. Various stressors, such as the conversion of natural habitats, climate change, land-use intensification, agrochemicals and pathogens, are thought to be major factors in this decline. We treated female bees of two common pollinator species in Europe, Osmia bicornis and Bombus terrestris, with a field-realistic dose of the neonicotinoid clothianidin. We tested its effects on the foraging behavior of O. bicornis under semi-natural conditions and on the antennal sensitivity of both bee species to common floral volatiles by using electroantennography. Clothianidin negatively affected the foraging behavior in O. bicornis by decreasing the number of flowers visited per foraging flight and by increasing the time per flower visit and the searching time between two flowers. It also decreased the antennal sensitivity to 2-phenylethanol in the two bee species. Thus, clothianidin is clearly a threat for bees via its effects on their foraging behavior and antennal sensitivity and is hence probably detrimental for pollination and the reproductive success of bees.

Abstract The baby‐friendly hospital initiative (BFHI) promotes exclusive breastfeeding (EBF) in hospitals, but this is not accessible in rural settings where mothers give birth at home, hence the need for a community intervention. We tested the effectiveness of the baby‐friendly community initiative (BFCI) on EBF in rural Kenya. This cluster randomized study was conducted in 13 community units in Koibatek sub‐county. Pregnant women aged 15–49 years were recruited and followed up until their children were 6 months old. Mothers in the intervention group received standard maternal, infant and young child nutrition counselling, support from trained community health volunteers, health professionals and community and mother support groups, whereas those in the control group received standard counselling only. Data on breastfeeding practices were collected longitudinally. The probability of EBF up to 6 months of age and the restricted mean survival time difference were estimated. A total of 823 (intervention group n = 351) pregnant women were recruited. Compared with children in the control group, children in the intervention group were more likely to exclusively breastfeed for 6 months (79.2% vs. 54.5%; P < .05). Children in the intervention group were also exclusively breastfed for a longer time, mean difference (95% confidence interval [CI]) 0.62 months (0.38, 0.85; P < .001). The BFCI implemented within the existing health system and including community and mother support groups led to a significant increase in EBF in a rural Kenyan setting. This intervention has the potential to improve EBF rates in similar settings.

Abstract The Kenyan Ministry of Health has developed a National Strategy on Infant and Young Child Feeding with the goal of improving feeding practices for infants and children. In order to promote appropriate infant feeding, the government has explored implementation of the Baby Friendly Community Initiative (BFCI). This study assessed maternal knowledge of attributes of complementary feeding following implementation of BFCI in Koibatek, Kenya. A randomized control study composed of 270 mother–infant pairs previously enrolled in a BFCI programme in Koibatek was conducted. The study found that a significantly greater number of mothers in the intervention group were more knowledgeable about proper breastfeeding and complementary feeding aspects compared with controls (P ≤ 0.001). About half (53%) of mothers in the intervention group had high knowledge scores in comparison with 20% of mothers in the control group. When the relationship between mothers' knowledge and complementary feeding practices (minimum meal frequency, minimum dietary diversity and minimum acceptable diet) was assessed, significant associations were observed (P = 0.010, P ≤ 0.001 and P ≤ 0.001, respectively). The odds of having a high knowledge score regarding complementary feeding practices were significantly higher for the intervention group compared with the control group (odds ratio [OR]: 25.98, 95% confidence interval [CI] 13.62–49.55, P ≤ 0.001). The BFCI intervention effectively improved mothers' knowledge on complementary feeding and correlated with improved feeding practices.

Metazoan PUF (Pumilio and FBF) RNA-binding proteins regulate various biological processes, but a common theme across phylogeny is stem cell regulation. In Caenorhabditis elegans, FBF (fem-3 Binding Factor) maintains germline stem cells regardless of which gamete is made, but FBF also functions in the process of spermatogenesis. We have begun to “disentangle” these biological roles by asking which FBF targets are gamete-independent, as expected for stem cells, and which are gamete-specific. Specifically, we compared FBF iCLIP binding profiles in adults making sperm to those making oocytes. Normally, XX adults make oocytes. To generate XX adults making sperm, we used a fem-3(gf) mutant requiring growth at 25°; for comparison, wild-type oogenic hermaphrodites were also raised at 25°. Our FBF iCLIP data revealed FBF binding sites in 1522 RNAs from oogenic adults and 1704 RNAs from spermatogenic adults. More than half of these FBF targets were independent of germline gender. We next clustered RNAs by FBF-RNA complex frequencies and found four distinct blocks. Block I RNAs were enriched in spermatogenic germlines, and included validated target fog-3, while Block II and III RNAs were common to both genders, and Block IV RNAs were enriched in oogenic germlines. Block II (510 RNAs) included almost all validated FBF targets and was enriched for cell cycle regulators. Block III (21 RNAs) was enriched for RNA-binding proteins, including previously validated FBF targets gld-1 and htp-1. We suggest that Block I RNAs belong to the FBF network for spermatogenesis, and that Blocks II and III are associated with stem cell functions.

Summary: FOG-3 is a master regulator of sperm fate in Caenorhabditis elegans and homologous to Tob/BTG proteins, which in mammals are monomeric adaptors that recruit enzymes to RNA binding proteins. Here, we determine the FOG-3 crystal structure and in vitro demonstrate that FOG-3 forms dimers that can multimerize. The FOG-3 multimeric structure has a basic surface potential, suggestive of binding nucleic acid. Consistent with that prediction, FOG-3 binds directly to nearly 1,000 RNAs in nematode spermatogenic germ cells. Most binding is to the 3′ UTR, and most targets (94%) are oogenic mRNAs, even though assayed in spermatogenic cells. When tethered to a reporter mRNA, FOG-3 represses its expression. Together these findings elucidate the molecular mechanism of sperm fate specification and reveal the evolution of a protein from monomeric to multimeric form with acquisition of a distinct mode of mRNA repression. : The mechanism of the sperm or oocyte fate decision has been elusive. Aoki et al. report that nematode FOG-3, a Tob/BTG protein driving sperm fate, has evolved from monomeric to multimeric form with acquisition of a divergent Tob/BTG mechanism for mRNA repression. Keywords: FOG-3, Tob/BTG, RNA binding protein, multimerization, protein evolution, sperm fate

Abstract Background Appropriate infant and young child nutrition is critical for proper growth and development. In order to promote optimal nutrition at an early age, the World Health Organization (WHO) and UNICEF have developed the Baby Friendly Hospital Initiative (BFHI) to address poor breastfeeding practices in maternity wards. However, impact is limited in less developed countries like Kenya, where more than half of all births are home deliveries. Therefore, Kenya has explored the adoption of Baby Friendly Community Initiative (BFCI) in its rural settings. In contrast to the BFHI, the BFCI supports breastfeeding and optimal infant feeding in community. BFCI has been implemented in Koibatek, in rural Kenya. This study aimed at assessing the effectiveness of BFCI on complementary feeding practices of children aged 6–23 months, by comparing intervention and control groups. Methods This was a randomized control study design that included 270 mother-infant pairs enrolled in the Baby Friendly Community Initiative (BFCI) project in Koibatek. Evaluation was carried out using structured questionnaires. Results A statistically significantly higher proportion of children in the intervention group compared to the control group attained minimum dietary diversity (77% vs. 58%; p = 0.001), minimum meal frequency (96% vs. 89%; p = 0.046) and minimum acceptable diet (77% vs. 61%; p = 0.005). The odds of attaining minimum dietary diversity, minimum meal frequency and minimum acceptable diet were statistically significantly higher for the intervention group compared to control group (OR: 4.95; 95%CI 2.44–10.03, p =

A cross-sectional study was conducted to assess dietary practices, nutrient adequacy, and nutrition status among 164 adolescents aged between 16 and 19 years in boarding secondary schools in the Kilimanjaro region. In-depth interviews and a survey guided by a semistructured and structured questionnaire, including 24-hour recall and food frequency questionnaire techniques, were used to collect information. Nutrition status was assessed using anthropometric measurements and hemoglobin levels. WHO AnthroPlus software and NutriSurvey software were used to analyze anthropometry and dietary data, respectively. Diet in boarding schools was monotonous comprising mainly of cereal-legume meal with low intake of animal sources, fruits, and vegetables. Mean intake of energy, vitamin C, iron, calcium, and zinc was 1392 kcal, 24.8 mg, 9.2 mg, 134.5 mg, and 4.3 mg, respectively, which were below the Recommended Daily Allowance. The average carbohydrate, fat, and protein intake of 471.9 g, 73.7 g, and 80.7 g, respectively, were slightly higher than the Recommended Daily Allowance in both sexes. Male had a significantly higher intake of protein and carbohydrates (P

Background. Childhood obesity is currently increasing at an alarming rate worldwide. Childhood obesity research has not been reported in urban Arusha before. This is therefore the first study to investigate the prevalence and predictors of childhood obesity in urban Arusha. Methods. A cross-sectional study was conducted involving 451 schoolchildren. Overweight was defined to range from 85th to 94th BMI percentile for age and sex while obesity was defined as above 94th BMI percentile for age and sex. Chi-square test was used for comparison between child sex and sociobehaviors, and multiple logistic regression was used to determine the significant predictor factors at P values = 0.05. Results. The overall prevalence of overweight and obesity was 17.7% (80/451) with 12.6% (57/451) being obese and 5.1% (23/451) being overweight. Results from univariate logistic regression showed child sex, random sleeping time, and random eating habit were the significant predictor factors. However, when all the predictor factors were used in the final multiple logistic regression model, only random sleeping time and random eating habit of different food items irrespective of their nature were significant at P=0.000, AOR = 4.47, and 95% CI = 2.00–10.01, and P=0.012, AOR = 2.54, and 95% CI = 1.23–5.33, respectively. Conclusions. The prevalence of obesity was as higher as twice the prevalence observed in other previous studies in Tanzania. Being a girl, random sleeping time and random eating habit were independent predictors. In addition to larger sample sizes, longitudinal studies are needed in order to track individuals and population level trends in BMI over time.

The article focuses on the U.S. court case United States ex rel. Elin Baklid-Kunz v. Halifax Hospital Medical Center, which dealt with the scope of attorney-client privilege for corporate lawyers. Topics include attorney-client privilege over documents submitted as evidence and qui tam filings under the U.S. False Claims Act (FCA).

Central questions in regenerative biology include how stem cells are maintained and how they transition from self-renewal to differentiation. Germline stem cells (GSCs) in Caeno-rhabditis elegans provide a tractable in vivo model to address these questions. In this system, Notch signaling and PUF RNA binding proteins, FBF-1 and FBF-2 (collectively FBF), maintain a pool of GSCs in a naïve state. An open question has been how Notch signaling modulates FBF activity to promote stem cell self-renewal. Here we report that two Notch targets, SYGL-1 and LST-1, link niche signaling to FBF. We find that SYGL-1 and LST-1 proteins are cytoplasmic and normally restricted to the GSC pool region. Increasing the distribution of SYGL-1 expands the pool correspondingly, and vast overexpression of either SYGL-1 or LST-1 generates a germline tumor. Thus, SYGL-1 and LST-1 are each sufficient to drive "stemness" and their spatial restriction prevents tumor formation. Importantly, SYGL-1 and LST-1 can only drive tumor formation when FBF is present. Moreover, both proteins interact physically with FBF, and both are required to repress a signature FBF mRNA target. Together, our results support a model in which SYGL-1 and LST-1 form a repressive complex with FBF that is crucial for stem cell maintenance. We further propose that progression from a naïve stem cell state to a state primed for differentiation relies on loss of SYGL-1 and LST-1, which in turn relieves FBF target RNAs from repression. Broadly, our results provide new insights into the link between niche signaling and a downstream RNA regulatory network and how this circuitry governs the balance between self-renewal and differentiation.

Single-molecule RNA fluorescence in situ hybridization (smFISH) is a technique to visualize individual RNA molecules using multiple fluorescently-labeled oligonucleotide probes specific to the target RNA (Raj et al., 2008; Lee et al., 2016a). We adapted this technique to visualize RNAs in the C. elegans whole adult worm or its germline, which enabled simultaneous recording of nascent transcripts at active transcription sites and mature mRNAs in the cytoplasm (Lee et al., 2013 and 2016b). Here we describe each step of the smFISH procedure, reagents, and microscope settings optimized for C. elegans extruded gonads.

C. elegans Notch signaling maintains a pool of germline stem cells within their single-celled mesenchymal niche. Here we investigate the Notch transcriptional response in germline stem cells using single-molecule fluorescence in situ hybridization coupled with automated, high-throughput quantitation. This approach allows us to distinguish Notch-dependent nascent transcripts in the nucleus from mature mRNAs in the cytoplasm. We find that Notch-dependent active transcription sites occur in a probabilistic fashion and, unexpectedly, do so in a steep gradient across the stem cell pool. Yet these graded nuclear sites create a nearly uniform field of mRNAs that extends beyond the region of transcriptional activation. Therefore, active transcription sites provide a precise view of where the Notch-dependent transcriptional complex is productively engaged. Our findings offer a new window into the Notch transcriptional response and demonstrate the importance of assaying nascent transcripts at active transcription sites as a readout for canonical signaling.

Many types of adult stem cells exist in a state of cell-cycle quiescence, yet it has remained unclear whether quiescence plays a role in maintaining the stem cell fate. Here we establish the adult germline of Caenorhabditis elegans as a model for facultative stem cell quiescence. We find that mitotically dividing germ cells—including germline stem cells—become quiescent in the absence of food. This quiescence is characterized by a slowing of S phase, a block to M-phase entry, and the ability to re-enter M phase rapidly in response to re-feeding. Further, we demonstrate that cell-cycle quiescence alters the genetic requirements for stem cell maintenance: The signaling pathway required for stem cell maintenance under fed conditions—GLP-1/Notch signaling—becomes dispensable under conditions of quiescence. Thus, cell-cycle quiescence can itself maintain stem cells, independent of the signaling pathway otherwise essential for such maintenance.

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Growth factors and transcription factors are well known to regulate pluripotent stem cells, but less is known about translational control in stem cells. Here, we use embryonic stem cells (ESCs) to investigate a connection between ESC growth factors and eIF2α-mediated translational control (eIF2α phosphorylation promotes protein expression from mRNAs with upstream open-reading frames, or uORFs). We find abundant phosphorylated P-eIF2α (P-eIF2α) in both pluripotent mouse and human ESCs, but little P-eIF2α in ESCs triggered to differentiate. We show that the growth factors LIF (leukemia inhibitory factor) and BMP4 (bone morphogenic protein 4) both maintain P-eIF2α in mESCs, but use distinct mechanisms: LIF inhibits an eIF2α phosphatase whereas BMP4 activates an eIF2α kinase. The mRNAs encoding the pluripotency factors Nanog and c-Myc possess uORFs while Oct4 mRNA does not. We find that salubrinal, a chemical that increases eIF2α phosphorylation, promotes Nanog and c-Myc expression, but not Oct4 expression. These experiments connect ESC growth factors to eIF2α phosphorylation and suggest a chemical substitute for LIF to enhance Nanog and c-Myc expression.

The mesenchymal distal tip cell (DTC) provides the niche for Caenorhabditis elegans germline stem cells (GSCs). The DTC has a complex cellular architecture: its cell body caps the distal gonadal end and contacts germ cells extensively, but it also includes multiple cellular processes that extend along the germline tube and intercalate between germ cells. Here we use the lag-2 DTC promoter to drive expression of myristoylated GFP, which highlights DTC membranes and permits a more detailed view of DTC architecture. We find that short processes intercalating between germ cells contact more germ cells than seen previously. We define this region of extensive niche contact with germ cells as the DTC plexus. The extent of the DTC plexus corresponds well with the previously determined extent of the GSC pool. Moreover, expression of a differentiation marker increases as germ cells move out of the plexus. Maintenance of this DTC plexus depends on the presence of undifferentiated germ cells, suggesting that germ cell state can influence niche architecture. The roles of this DTC architecture remain an open question. One idea is that the DTC plexus delivers Notch signaling to the cluster of germ cells comprising the GSC pool; another idea is that the plexus anchors GSCs at the distal end.

Coordination of the cell cycle with developmental events is crucial for generation of tissues during development and their maintenance in adults. Defects in that coordination can shift the balance of cell fates with devastating clinical effects. Yet our understanding of the molecular mechanisms integrating core cell cycle regulators with developmental regulators remains in its infancy. This work focuses on the interplay between cell cycle and developmental regulators in the Caenorhabditis elegans germline. Key developmental regulators control germline stem cells (GSCs) to self-renew or begin differentiation: FBF RNA-binding proteins promote self-renewal, while GLD RNA regulatory proteins promote meiotic entry. We first discovered that many but not all germ cells switch from the mitotic into the meiotic cell cycle after RNAi depletion of CYE-1 (C. elegans cyclin E) or CDK-2 (C. elegans Cdk2) in wild-type adults. Therefore, CYE-1/CDK-2 influences the mitosis/meiosis balance. We next found that GLD-1 is expressed ectopically in GSCs after CYE-1 or CDK-2 depletion and that GLD-1 removal can rescue cye-1/cdk-2 defects. Therefore, GLD-1 is crucial for the CYE-1/CDK-2 mitosis/meiosis control. Indeed, GLD-1 appears to be a direct substrate of CYE-1/CDK-2: GLD-1 is a phosphoprotein; CYE-1/CDK-2 regulates its phosphorylation in vivo; and human cyclin E/Cdk2 phosphorylates GLD-1 in vitro. Transgenic GLD-1(AAA) harbors alanine substitutions at three consensus CDK phosphorylation sites. GLD-1(AAA) is expressed ectopically in GSCs, and GLD-1(AAA) transgenic germlines have a smaller than normal mitotic zone. Together these findings forge a regulatory link between CYE-1/CDK-2 and GLD-1. Finally, we find that CYE-1/CDK-2 works with FBF-1 to maintain GSCs and prevent their meiotic entry, at least in part, by lowering GLD-1 abundance. Therefore, CYE-1/CDK-2 emerges as a critical regulator of stem cell maintenance. We suggest that cyclin E and Cdk-2 may be used broadly to control developmental regulators.

Many animals alter their reproductive strategies in response to environmental stress. Here we have investigated how L4 hermaphrodites of Caenorhabditis elegans respond to starvation. To induce starvation, we removed food at 2 h intervals from very early- to very late-stage L4 animals. The starved L4s molted into adulthood, initiated oogenesis, and began producing embryos; however, all three processes were severely delayed, and embryo viability was reduced. Most animals died via 'bagging,' because egg-laying was inhibited, and embryos hatched in utero, consuming their parent hermaphrodites from within. Some animals, however, avoided bagging and survived long term. Long-term survival did not rely on embryonic arrest but instead upon the failure of some animals to produce viable progeny during starvation. Regardless of the bagging fate, starved animals showed two major changes in germline morphology: All oogenic germlines were dramatically reduced in size, and these germlines formed only a single oocyte at a time, separated from the remainder of the germline by a tight constriction. Both changes in germline morphology were reversible: Upon re-feeding, the shrunken germlines regenerated, and multiple oocytes formed concurrently. The capacity for germline regeneration upon re-feeding was not limited to the small subset of animals that normally survive starvation: When bagging was prevented ectopically by par-2 RNAi, virtually all germlines still regenerated. In addition, germline shrinkage strongly correlated with oogenesis, suggesting that during starvation, germline shrinkage may provide material for oocyte production. Finally, germline shrinkage and regeneration did not depend upon crowding. Our study confirms previous findings that starvation uncouples germ cell proliferation from germline stem cell maintenance. Our study also suggests that when nutrients are limited, hermaphrodites scavenge material from their germlines to reproduce. We discuss our findings in light of the recently proposed state of dormancy, termed Adult Reproductive Diapause.

Mitogen-activated protein kinase (MAPK) and PUF (for Pumilio and FBF [fem-3 binding factor]) RNA-binding proteins control many cellular processes critical for animal development and tissue homeostasis. In the present work, we report that PUF proteins act directly on MAPK/ERK-encoding mRNAs to downregulate their expression in both the Caenorhabditis elegans germline and human embryonic stem cells. In C. elegans, FBF/PUF binds regulatory elements in the mpk-1 3' untranslated region (3' UTR) and coprecipitates with mpk-1 mRNA; moreover, mpk-1 expression increases dramatically in FBF mutants. In human embryonic stem cells, PUM2/PUF binds 3'UTR elements in both Erk2 and p38alpha mRNAs, and PUM2 represses reporter constructs carrying either Erk2 or p38alpha 3' UTRs. Therefore, the PUF control of MAPK expression is conserved. Its biological function was explored in nematodes, where FBF promotes the self-renewal of germline stem cells, and MPK-1 promotes oocyte maturation and germ cell apoptosis. We found that FBF acts redundantly with LIP-1, the C. elegans homolog of MAPK phosphatase (MKP), to restrict MAPK activity and prevent apoptosis. In mammals, activated MAPK can promote apoptosis of cancer cells and restrict stem cell self-renewal, and MKP is upregulated in cancer cells. We propose that the dual negative regulation of MAPK by both PUF repression and MKP inhibition may be a conserved mechanism that influences both stem cell maintenance and tumor progression.