Protective effects of hachimijiogan (HJG), a Japanese Kampo medicine, on cancer cachectic muscle wasting in mice.

Myogenesis is required to generate skeletal muscle tissue and to maintain skeletal muscle mass. Decreased myogenesis under various pathogenic conditions results in muscular atrophy. Through a small screening of Japanese traditional (Kampo) medicines, hachimijiogan (HJG) was shown to promote the myogenic differentiation of C2C12 myoblasts through the upregulation of myogenin. In tumor-bearing cancer-cachectic mice, HJG was also found to have a protective effect against cancer-cachectic muscle wasting. This effect was significant when HJG was administered in combination with aerobic exercise by treadmill running. Moreover, HJG ameliorated the cellular atrophy of C2C12 myotubes induced by treatment with conditioned medium derived from a colon-26 cancer cell culture. In addition, HJG suppressed H2O2-dependent myotube atrophy, suggesting that HJG could reverse the atrophic phenotypes by eliminating reactive oxygen species.

Trend of risk and correlates of under-five child undernutrition in Bangladesh: an analysis based on Bangladesh Demographic and Health Survey data, 2007-2017/2018.

OBJECTIVES: The objectives of this study are to identify the trend of undernutrition risk among under-five children (U5C) in Bangladesh and the trend of its correlates. DESIGN: Multiple cross-sectional data sets from different time points were used. SETTING: Nationally representative Bangladesh Demographic and Health Surveys (BDHSs) were conducted in 2007, 2011, 2014 and 2017/2018. PARTICIPANTS: In the BDHSs, the sample sizes for ever-married women (age: 15-49 years) were 5300 in 2007, 7647 in 2011, 6965 in 2014 and 7902 in 2017/2018. OUTCOMES: Extant indicators of undernutrition (stunted, wasted and underweight) have been considered as the outcome variables. MATERIALS AND METHODS: Descriptive statistics, bivariate analysis and factor loadings from factor analysis have been used to determine the prevalence of undernutrition over the years and find the trend of risk and its correlates. RESULTS: Risks of stunting among the U5C were 41.70%, 40.67%, 36.57% and 31.14%; that of wasting were 16.94%, 15.48%, 14.43% and 8.44%; and that of underweight were 39.79%, 35.80%, 32.45% and 22.46% in 2007, 2011, 2014 and 2017/2018, respectively. From the factor analysis, it has been found that the top five potential correlates of undernutrition are the wealth index, the education of the father and mother, the frequency of antenatal visits during pregnancy, the father's occupation and/or the type of place of residence in the last four consecutive surveys. CONCLUSION: This study helps us gain a better understanding of the impact of the top correlates on child undernutrition. To accelerate the reduction of child undernutrition more by 2030, Government and non-government organisations should focus on improving education and household income-generating activities among poor households and raising awareness among women about the importance of receiving antenatal care during pregnancy.

Understanding Child Wasting in Ethiopia: Cross-sectional Analysis of 2019 Ethiopian Demographic and Health Survey Data Using Generalized Linear Latent and Mixed Models.

BACKGROUND: Wasting is an immediate, visible, and life-threatening form of undernutrition in children aged <5 years. Within a short time, wasting causes recurrent sickness, delayed physical and mental growth, impatience, poor feeding, and low body weight. The long-term consequences of wasting and undernutrition are stunting, inability to learn, poor health status, and poor work performance. Wasting remains a public health problem in Ethiopia. According to the World Health Organization, countries have to reduce undernutrition including child wasting to below 5% by 2025. Ethiopia is attempting to attain national and international targets of undernutrition while struggling with many problems. OBJECTIVE: This study aimed to identify the prevalence and associated factors of wasting to provide information for further renewing policy commitments. METHODS: We used community-based, cross-sectional data from the Ethiopian Mini Demographic and Health Survey. The survey was conducted in 9 regions and 2 city administrations. Two-stage cluster sampling was used to recruit study participants. In the first stage, enumerations areas were selected, and 28-35 households per enumeration area were selected in the second stage. Our analysis included 2016 women with children aged <5 years from the 2019 EMDHS data set. We dropped incomplete records and included all women who fulfilled the eligibility criteria. We used multilevel ordinal regression using Generalized Linear Latent and Mixed Models (GLLAMM) and predicted probability with log-likelihood ratio tests. Fulfilling the proportional odds model's assumption during the application of multilevel ordinary logistic regression was a cumbersome task. GLLAMM enabled us to perform the multilevel proportional odds model using an alternative method. RESULTS: In our analysis, wasting was 7.68% (95% CI 6.56%-8.93%). Around 26.82% of mothers never used antenatal care for their current child. Most mothers (52.2%) did not have formal education, and 86.8% did not have postnatal care for their children. Additionally, half (50.93%) of the mothers have ≥6 household members. Wasting was associated with feeding diverse foods (coefficient 4.90, 95% CI 4.90-4.98), female sex of the household head (-40.40, 95% CI -40.41 to -40.32), home delivery (-35.51, 95% CI -35.55 to -35.47), first (16.66, 95% CI, 16.60-16.72) and second (16.65, 95% CI 16.60-16.70) birth order, female child (-12.65, 95% CI -12.69 to -12.62), and household size of 1 to 3 (10.86, 95% CI 10.80-10.92). CONCLUSIONS: According to the target set by World Health Organization for reducing undernutrition in children aged <5 years to below 5% by 2025, child wasting of 7.68% in Ethiopia should spark an immediate reaction from the government and stakeholders. Informed policy decisions, technology-based child-feeding education, and food self-sufficiency support could improve the current challenges. Additional effort is important to improve low maternal education, family planning, awareness of sex preferences, women empowerment, and maternal health services.

How Can Nutrition Research Better Reflect the Relationship Between Wasting and Stunting in Children? Learnings from the Wasting and Stunting Project.

Childhood wasting and stunting affect large numbers of children globally. Both are important risk factors for illness and death yet, despite the fact that these conditions can share common risk factors and are often seen in the same child, they are commonly portrayed as relatively distinct manifestations of undernutrition. In 2014, the Wasting and Stunting project was launched by the Emergency Nutrition Network. Its aim was to better understand the complex relationship and associations between wasting and stunting and examine whether current separations that were apparent in approaches to policy, financing, and programs were justified or useful. Based on the project's work, this article aims to bring a wasting and stunting lens to how research is designed and financed in order for the nutrition community to better understand, prevent, and treat child undernutrition. Discussion of lessons learnt focuses on the synergy and temporal relationships between children's weight loss and linear growth faltering, the proximal and distal factors that drive diverse forms of undernutrition, and identifying and targeting people most at risk. Supporting progress in all these areas requires research collaborations across interest groups that highlight the value of research that moves beyond a focus on single forms of undernutrition, and ensures that there is equal attention given to wasting as to other forms of malnutrition, wherever it is present.

Risk factors associated with under-five stunting, wasting, and underweight in four provinces of the Democratic Republic of Congo: analysis of the ASSP project baseline data.

BACKGROUND: Determining the magnitude and risk factors of undernutrition in a country that has one of the highest prevalence of undernutrition in the world is paramount for developing contextual interventions. METHODS: This study used baseline data from the ASSP project to estimate prevalence of stunting, wasting, and underweight in four provinces of DRC. It involved 3911 children aged 0-59 months old and mother pairs. Height-for-age Z scores, Weight-for-height Z scores, and Weight-for-age Z scores were calculated and used to classify child stunting, wasting and underweight respectively, based on the 2006 World Health Organization (WHO) growth reference. Hierarchical logistic regressions were used to identify risk factors associated with stunting, wasting and underweight. All analyses were conducted using STATA 15.1, and statistical significance was set at p < 0.05. RESULTS: The prevalence of stunting, underweight and wasting was 42.7%, 21.9% and 8.2% respectively. Increasing child's age was a risk factor associated with stunting and underweight, while sex was not associated with the 3 indicators of undernutrition. Low levels of mother's education, mothers working in the last 12 months prior to the survey, children living in the province of Kasai occidental, children born at a health facility, children perceived by their mothers to be born very small were associated with higher risks of stunting. Factors associated with underweight were children from the province of Kasai occidental, mothers who worked in the last 12 months prior to the survey, and children perceived to be born very small or small by their mothers. Children born to mothers aged 35-49 years and children breastfed in combination with drinking water were at higher risk of wasting. CONCLUSION: Prevalence of undernutrition in DRC is high. This study has identified certain modifiable risk factors associated with stunting, wasting and underweight. To reduce the burden of undernutrition in DRC, authorities should target factors at individual and community levels by improving women's education, child feeding practices and promoting agriculture.

Risk factors of stunting and wasting in Somali pre-school age children: results from the 2019 Somalia micronutrient survey.

BACKGROUND: Stunting and wasting in children less than 5 years of age are two key indicators of child malnutrition. Reducing their prevalence is a priority of the global public health community and for Somalia, a country suffering complex humanitarian emergencies such as drought, flooding, conflict and large-scale displacements. METHODS: Data from the nationally representative cross-sectional Somalia Micronutrient Survey (SMS 2019) on 1947 children were analyzed to assess the prevalence and potential risk factors of stunting and wasting. Bivariate and multivariable analyses were conducted separately for children 0-5 months and 6-59 months, and population attributable fractions were calculated using adjusted risk ratios produced by Poisson regression models. RESULTS: Among the 1947 children, the prevalence of stunting and wasting were 17.2% (95% CI: 15.0, 19.6) and 11.0% (95% CI: 9.3, 12.9), respectively. Among children 6-59 months of age, those residing in severely food insecure households had a higher risk of stunting (adjusted risk ratio [aRR] 1.47; CI: 1.12, 1.93) compared to those in food secure households. This risk of stunting was also higher in children with inflammation (aRR 1.75; CI: 1.35, 2.25) and iron deficiency (ID) (aRR 2.09; CI: 1.58, 2.80). For wasting, a dose-response relationship was found with household wealth, with the risk of wasting increasing significantly as the household wealth quintile decreased. On the other hand, the risk of wasting was lower in iron-deficient children (aRR 0.69; CI: 0.49, 0.98) than in iron-replete children. Among children 0-5 months of age no variables remained statistically significantly associated with stunting in the multivariable analysis. Wasting, however, was more common in children with recent diarrhea (aRR 3.51; CI: 1.68, 7.36). CONCLUSIONS: Nutritional status of children in Somalia may be improved by prevention of diarrhea and other infections and improvements in household food security.

Cachectic muscle wasting in acute myeloid leukaemia: a sleeping giant with dire clinical consequences.

Acute myeloid leukaemia (AML) is a haematological malignancy with poor survival odds, particularly in the older (>65 years) population, in whom it is most prevalent. Treatment consists of induction and consolidation chemotherapy to remit the cancer followed by potentially curative haematopoietic cell transplantation. These intense treatments are debilitating and increase the risk of mortality. Patient stratification is used to mitigate this risk and considers a variety of factors, including body mass, to determine whether a patient is suitable for any or all treatment options. Skeletal muscle mass, the primary constituent of the body lean mass, may be a better predictor of patient suitability for, and outcomes of, AML treatment. Yet skeletal muscle is compromised by a variety of factors associated with AML and its clinical treatment consistent with cachexia, a life-threatening body wasting syndrome. Cachectic muscle wasting is associated with both cancer and anticancer chemotherapy. Although not traditionally associated with haematological cancers, cachexia is observed in AML and can have dire consequences. In this review, we discuss the importance of addressing skeletal muscle mass and cachexia within the AML clinical landscape in view of improving survivability of this disease.

Concurrent central diabetes insipidus and cerebral salt wasting disease in a post-operative case of craniopharyngioma: a case report.

BACKGROUND: Water and electrolyte disorders commonly encountered in children post-surgery involving hypothalamus and posterior pituitary, are central diabetes insipidus, syndrome of inappropriate secretion of anti-diuretic hormone and cerebral salt wasting disease. Delayed diagnosis and inadequate management of such cases may lead to worsened neurological outcomes with a high mortality rate. CASE PRESENTATION: Here we report the case of a 7-year-old girl who underwent surgical resection of a craniopharyngioma, following which she initially developed central diabetes insipidus. However, later on in the course of her illness she developed symptomatic hyponatremia with natriuresis which was diagnosed to be due to cerebral salt wasting disease. This combination of central diabetes insipidus and cerebral salt wasting syndrome is a rare occurrence and poses a diagnostic challenge. Diagnosis and management can be even more difficult when these conditions precede or coexist with each other. CONCLUSION: In such cases development of hyponatremia should always prompt consideration of unusual causes like cerebral salt wasting disease in addition to the classically described syndrome of inappropriate secretion of anti-diuretic hormone. Hence, a thorough knowledge of these disorders along with intensive monitoring of fluid and sodium status is critical for timely diagnosis and management of these patients.

Impact of frailty and its inter-relationship with lean tissue wasting and malnutrition on kidney transplant waitlist candidacy and delisting.

BACKGROUND & AIMS: Frailty and body composition contribute to adverse pre-transplant outcomes including hospitalization and waitlist mortality, but the interaction between frailty and body composition remains uncertain. METHODS: Frailty was diagnosed by Clinical Frailty Scale (CFS) and a standard Frailty Questionnaire (FQ). Nutrition was evaluated by serum albumin level, subjective global assessment (SGA) and comprehensive malnutrition-inflammation score (MIS). Body composition was assessed by bioimpedance spectroscopy. All patients were followed up for three years. Primary outcome measure was a composite of death and permanent removal from waitlist. Secondary outcomes were emergency room attendance and hospitalization. RESULTS: 432 prevalent peritoneal dialysis (PD) patients were recruited. 148 (34.3%) were listed on transplant waitlist. Frailty, age and comorbidity load predicted waitlisting. With time, 47 patients were delisted. Frailty by FQ (p = 0.028), serum albumin level (p = 0.005) and waist circumference (p = 0.010) predicted delisting after adjustment for confounders. Frailty significantly interacted with lean tissue wasting (FQ: p = 0.002, CFS: p = 0.048), and MIS (FQ: p = 0.004; CFS: p = 0.014) on delisting. Lean tissue wasting caused 2.56 times risk of delisting among frail individuals identified by FQ (p = 0.016), while serum albumin and the presence of diabetes mellitus predicted the risk of delisting among non-frail individuals. Lean tissue wasted and frail subjects had a higher all-cause and infection-related hospitalization. CONCLUSION: Frailty predicted both kidney transplant waitlisting and subsequent delisting. Frailty interacted with body composition on transplant waitlist delisting. Lean tissue wasting and malnutrition independently predicted delisting in frail and non-frail listed subjects respectively.

Impact of children born with low birth weight on stunting and wasting in Sindh province of Pakistan: a propensity score matching approach.

Low Birth Weight (LBW) is considered as a major public health issue and leading cause of neonatal death. Almost one in four newborns are reported as underweight in Pakistan. Children born with low birth weight are highly vulnerable to develop diseases and death and/or remain undernourished (i.e., stunted and wasted). This study determines the LBW newborns are more prone to develop stunting and wasting in province of Sindh, Pakistan. Moreover, regression-based estimation of the impact of LBW on the child health outcomes of under five years of age, may be prone to selection bias because of the nature of non-experimental data set, thus, propensity score matching methods are used in this study. Data for this study was used from Multiple Indicators Cluster Survey (MICS-2014). MICS is a two-stage, stratified cluster sampling household level data covering urban and rural areas and consists of 19,500 households from five administrative divisions and 28 districts of Sindh province of Pakistan. The total sample size of children less than five years of age after cleaning the data are 7781, of which 2095 are LBW having birth weight categorized as "smaller than average and very small" and 5686 are normal birth weight (NBW) having birth weight very large, larger than average, and average. This study employed propensity score matching (PSM) regression methods to understand whether the children born as low birth weight are more prone to stunting and wasting and/or both. In province of Sindh, moderate wasting children under five years were 21%, severe wasting 6% and both wasting and stunting 10%. The propensity score results are shown significant in all groups. Specifically, all four types of PSM methods confirm a significant difference in the potential outcome variables-meaning that a child born with LBW has a significant adverse effect on the potential child health outcome variables (stunting, wasting and both). Thus, the propensity score matching findings confirm a significant and adverse effect of LBW on potential health outcomes of under five children. Similarly, low birth weight children are significantly more likely to be moderately wasted (OR = 1.5, CI = 1.3-1.6) and severely wasted (OR = 1.6, CI = 1.3-2.0) and both (stunted and wasted, OR = 2.0, CI = 1.7-2.3) as compared to children with normal birth weight. Male children, if born with low birth weight, are significantly more likely to be moderately wasted (OR = 1.3, CI = 1.1-1.5) and both (wasted and stunted, OR = 1.3, CI = 1.1-1.5) than girls. This large data analysis finding proved that the LBW newborns are on higher risk to develop wasting and stunting in Pakistan.

The Joint Effect of Maternal Marital Status and Type of Household Cooking Fuel on Child Nutritional Status in Sub-Saharan Africa: Analysis of Cross-Sectional Surveys on Children from 31 Countries.

The current study sought to investigate the joint effect of maternal marital status and type of household cooking fuel on child nutritional status in sub-Saharan Africa. Data in the children's files of 31 sub-Saharan African countries were pooled from the Demographic and Health Surveys collected between 2010 and 2019. The outcome variables were three child anthropometrics: stunting (height-for-age z-scores); wasting (weight-for-height z-scores); and underweight (weight-for-age z-scores). The joint effect of maternal marital status and type of household cooking fuel on child nutritional status was examined using multilevel regression models. The results were presented as adjusted odds ratios (aORs) at p < 0.05. The percentages of children who were stunted, wasted and underweight in the 31 countries in sub-Saharan Africa were 31%, 8% and 17%, respectively. On the joint effect of maternal marital status and type of household cooking fuel on stunting, we found that compared to children born to married mothers who used clean household cooking fuel, children born to single mothers who use unclean household cooking fuel, children born to single women who use clean household cooking fuel, and children born to married women who used unclean household cooking were more likely to be stunted. With wasting, children born to single mothers who used unclean household cooking fuel and children born to married women who used unclean household cooking fuel were more likely to be wasted compared to children born to married mothers who used clean household cooking fuel. With underweight, we found that compared to children born to married mothers who used clean household cooking fuel, children born to single mothers who used unclean household cooking fuel, children born to single women who used clean household cooking fuel and children born to married women who used unclean household cooking were more likely to be underweight. It is imperative for the governments of the 31 sub-Saharan African countries to double their efforts to end the use of unclean household cooking fuel. This goal could be achieved by promoting clean household cooking fuel (e.g., electricity, gas, ethanol, solar, etc.) through effective health education, and promotion programmes. The attention of policymakers is drawn to the urgent need for children's nutritional status policies and programmes (e.g., dietary supplementation, increasing dietary diversity, improving agriculture and food security) to be targeted towards at-risk sub-populations (i.e., single mothered households).

Investigate the risk factors of stunting, wasting, and underweight among under-five Bangladeshi children and its prediction based on machine learning approach.

AIMS: Malnutrition is a major health issue among Bangladeshi under-five (U5) children. Children are malnourished if the calories and proteins they take through their diet are not sufficient for their growth and maintenance. The goal of the research was to use machine learning (ML) algorithms to detect the risk factors of malnutrition (stunted, wasted, and underweight) as well as their prediction. METHODS: This work utilized malnutrition data that was derived from Bangladesh Demographic and Health Survey which was conducted in 2014. The selected dataset consisted of 7079 children with 13 factors. The potential risks of malnutrition have been identified by logistic regression (LR). Moreover, 3 ML classifiers (support vector machine (SVM), random forest (RF), and LR) have been implemented for predicting malnutrition and the performance of these ML algorithms were assessed on the basis of accuracy. RESULTS: The average prevalence of stunted, wasted, and underweight was 35.4%, 15.4%, and 32.8%, respectively. It was noted that LR identified five risk factors for stunting and underweight, as well as four factors for wasting. Results illustrated that RF can be accurately classified as stunted, wasted, and underweight children and obtained the highest accuracy of 88.3% for stunted, 87.7% for wasted, and 85.7% for underweight. CONCLUSION: This research focused on the identification and prediction of major risk factors for stunting, wasting, and underweight using ML algorithms which will aid policymakers in reducing malnutrition among Bangladesh's U5 children.

Pro-cachectic factors link experimental and human chronic kidney disease to skeletal muscle wasting programs.

Skeletal muscle wasting is commonly associated with chronic kidney disease (CKD), resulting in increased morbidity and mortality. However, the link between kidney and muscle function remains poorly understood. Here, we took a complementary interorgan approach to investigate skeletal muscle wasting in CKD. We identified increased production and elevated blood levels of soluble pro-cachectic factors, including activin A, directly linking experimental and human CKD to skeletal muscle wasting programs. Single-cell sequencing data identified the expression of activin A in specific kidney cell populations of fibroblasts and cells of the juxtaglomerular apparatus. We propose that persistent and increased kidney production of pro-cachectic factors, combined with a lack of kidney clearance, facilitates a vicious kidney/muscle signaling cycle, leading to exacerbated blood accumulation and, thereby, skeletal muscle wasting. Systemic pharmacological blockade of activin A using soluble activin receptor type IIB ligand trap as well as muscle-specific adeno-associated virus-mediated downregulation of its receptor ACVR2A/B prevented muscle wasting in different mouse models of experimental CKD, suggesting that activin A is a key factor in CKD-induced cachexia. In summary, we uncovered a crosstalk between kidney and muscle and propose modulation of activin signaling as a potential therapeutic strategy for skeletal muscle wasting in CKD.

Multivariate logistic regression analysis on the association between anthropometric indicators of under-five children in Nigeria: NDHS 2018.

BACKGROUND: Child malnutrition is a huge health problem having multifaceted consequences for child survival and long-term well-being. Although, several studies investigated stunting, underweight, and wasting in low- and middle-income countries, in Nigeria, the link between them received little attention. The aim of this study is, therefore, to assess the association between anthropometric indicators of under-five children such as stunting, underweight and wasting given that of other characteristics of children and households. METHODS: The data for this study was obtained from Nigerian Demographic and health survey (NDHS) in 2018. A total of 11,314 under-five children were involved. Multivariate logistic regression model was used to determine the association between stunting, underweight and wasting given that of the estimated effect of other determinants. RESULTS: From 11,314 under-five children the study considered 36.2, 21.4 and 6.7% of them suffered from stunting, underweight and wasting, respectively. About half (50.7%) of the children were male, 24.1% was obtained from North West region of Nigeria, and 37.8% of them were from households having unimproved drinking water. The pairwise dependency between stunting and underweight; underweight and wasting was measured using odds ratio (OR) of 15.796, and 16.750 respectively. The estimated odds of children from richest household to become stunted, underweight, and wasted was respectively 0.392, 0.540, 0.786 times that of the estimated odds of children from poorest households. CONCLUSION: The prevalence of under-five children with stunting, underweight and/or wasting in Nigeria was very high. The important determinants of stunting, underweight, and wasting for under five children were household wealth index, women body mass index, sex of the child, anemia, mothers' age at first birth, and a diarrhea two weeks prior to the survey. Whereas, region, religion, multiple birth, women's educational level significantly associated with both stunting and underweight. Both stunting and wasting significantly associated with underweight.

The Clinical Value of Nutritional Care before and during Active Cancer Treatment.

Malnutrition and muscle wasting are frequently reported in cancer patients, either linked to the tumor itself or caused by oncologic therapies. Understanding the value of nutritional care during cancer treatment remains crucial. In fact, cancer-associated sarcopenia plays a key role in determining higher rates of morbidity, mortality, treatment-induced toxicities, prolonged hospitalizations and reduced adherence to anticancer treatment, worsening quality of life and survival. Planning baseline screening to intercept nutritional troubles earlier, organizing timely reassessments, and providing adequate counselling and dietary support, healthcare professional may positively interfere with this process and improve patients' overall outcomes during the whole disease course. Several screening tools have been proposed for this purpose. Nutritional Risk Screening (NRS), Mini Nutritional Assessment (MNA), Patient Generated Subjective Global Assessment (PG-SGA) are the most common studied. Interestingly, second-level tools including skeletal muscle index (SMI) and bioelectric impedance analysis (BIA) provide a more precise assessment of body composition, even if they are more complex. However, nutritional assessment is not currently used in clinical practice and procedures must be standardized in order to improve the efficacy of standard chemotherapy, targeted agents or even checkpoint inhibitors that is potentially linked with the patients' nutritional status. In the present review, we will discuss about malnutrition and the importance of an early nutritional assessment during chemotherapy and treatment with novel checkpoint inhibitors, in order to prevent treatment-induced toxicities and to improve survival outcomes.

Wasting and Stunting in Infants and Young Children as Risk Factors for Subsequent Stunting or Mortality: Longitudinal Analysis of Data from Malawi, South Africa, and Pakistan.

BACKGROUND: Few studies have had sufficient longitudinal data to track how different malnourished states relate to mortality at different ages and interrelate over time. OBJECTIVES: This study aims to describe the RRs and proportions of mortality associated with wasting and stunting and the pathways into and out of these nutritional states. METHODS: Longitudinal growth data sets collected for children ages 0-24 months from Malawi, South Africa, and Pakistan were combined (n = 5088). Children were classified as deceased, wasted (weight for height < -2 SD; 1-4%), stunted (length < -2SD; 20-47%), or wasted and stunted (WaSt; 2-5%) at ages 3, 6, 9, 12, 18, and 24 months. Mixed-effects Cox models were used to study the association between nutritional status and mortality. RESULTS: By age 3 months, 20% of children were already stunted, rising to 49% by 24 months, while wasting (4.2% and 2.2% at 3 months, respectively) and WaSt (0.9% and 3.7% at 24 months, respectively) were less common. The HR for mortality in WaSt was 9.5 (95% CI, 5.9-15), but 60% of WaSt-associated mortality occurred at 3-6 months. Wasting or WaSt was associated with 10-23% of deaths beyond 6 months, but in the second year over half of deaths occurred in stunted, nonwasted children. Stunting persisted in 82% of children and wasting persisted in 44%. Wasted children were more likely than nonwasted, nonstunted children to become stunted (RR, 1.93; 95% CI, 1.7-2.2), but 94% of children who progressed to stunting had not been wasted in the prior period. CONCLUSIONS: WaSt greatly increased the risk of death, particularly in very young infants, but more deaths overall were associated with stunting. Most stunting appeared to be either intrauterine in origin or arose in children without prior wasting. Either stunting and wasting represent alternative responses to restricted nutrition, or stunting also has other, nonnutritional causes.

A Pilot Study of Gut-Brain Signaling After Octreotide Therapy for Unintentional Weight Loss After Esophagectomy.

BACKGROUND: Recurrence-free patients after esophageal cancer surgery face long-term nutritional consequences, occurring in the context of an exaggerated postprandial gut hormone response. Acute gut hormone suppression influences brain reward signaling and eating behavior. This study aimed to suppress gut hormone secretion and characterize reward responses and eating behavior among postesophagectomy patients with unintentional weight loss. METHODS: This pilot study prospectively studied postoperative patients with 10% or greater body weight loss (BWL) beyond 1 year who were candidates for clinical treatment with long-acting octreotide (LAR). Before and after 4 weeks of treatment, gut hormone secretion, food cue reactivity (functional magnetic resonance imaging), eating motivation (progressive ratio task), ad libitum food intake, body composition, and symptom burden were assessed. RESULTS: Eight patients (7 male, age: mean ±â€…SD 62.8 ±â€…9.4 years, postoperative BWL: 15.5 ±â€…5.8%) participated. Octreotide LAR did not significantly suppress total postprandial plasma glucagon-like peptide-1 response at 4 weeks (P = .08). Postprandial symptom burden improved after treatment (Sigstad score median [range]: 12 [2-28] vs 8 [3-18], P = .04) but weight remained stable (pre: 68.6 ±â€…12.8 kg vs post: 69.2 ±â€…13.4 kg, P = .13). There was no significant change in brain reward system responses, during evaluation of high-energy or low-energy food pictures, nor their appeal rating. Moreover, treatment did not alter motivation to eat (P = .41) nor ad libitum food intake(P = .46). CONCLUSION: The protocol used made it feasible to characterize the gut-brain axis and eating behavior in this cohort. Inadequate suppression of gut hormone responses 4 weeks after octreotide LAR administration may explain the lack of gut-brain pathway alterations. A higher dose or shorter interdose interval may be required to optimize the intervention.

Metabolic reprogramming and epigenetic changes of vital organs in SARS-CoV-2-induced systemic toxicity.

Extrapulmonary manifestations of COVID-19 are associated with a much higher mortality rate than pulmonary manifestations. However, little is known about the pathogenesis of systemic complications of COVID-19. Here, we create a murine model of SARS-CoV-2-induced severe systemic toxicity and multiorgan involvement by expressing the human ACE2 transgene in multiple tissues via viral delivery, followed by systemic administration of SARS-CoV-2. The animals develop a profound phenotype within 7 days with severe weight loss, morbidity, and failure to thrive. We demonstrate that there is metabolic suppression of oxidative phosphorylation and the tricarboxylic acid (TCA) cycle in multiple organs with neutrophilia, lymphopenia, and splenic atrophy, mirroring human COVID-19 phenotypes. Animals had a significantly lower heart rate, and electron microscopy demonstrated myofibrillar disarray and myocardial edema, a common pathogenic cardiac phenotype in human COVID-19. We performed metabolomic profiling of peripheral blood and identified a panel of TCA cycle metabolites that served as biomarkers of depressed oxidative phosphorylation. Finally, we observed that SARS-CoV-2 induces epigenetic changes of DNA methylation, which affects expression of immune response genes and could, in part, contribute to COVID-19 pathogenesis. Our model suggests that SARS-CoV-2-induced metabolic reprogramming and epigenetic changes in internal organs could contribute to systemic toxicity and lethality in COVID-19.

The Aryl Hydrocarbon Receptor in Energy Balance: The Road from Dioxin-Induced Wasting Syndrome to Combating Obesity with Ahr Ligands.

The aryl hydrocarbon receptor (AHR) has been studied for over 40 years, yet our understanding of this ligand-activated transcription factor remains incomplete. Each year, novel findings continually force us to rethink the role of the AHR in mammalian biology. The AHR has historically been studied within the context of potent activation via AHR agonist 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), with a focus on how the AHR mediates TCDD toxicity. Research has subsequently revealed that the AHR is actively involved in distinct physiological processes ranging from the development of the liver and reproductive organs, to immune system function and wound healing. More recently, the AHR was implicated in the regulation of energy metabolism and is currently being investigated as a potential therapeutic target for obesity. In this review, we re-trace the steps through which the early toxicological studies of TCDD led to the conceptual framework for the AHR as a potential therapeutic target in metabolic disease. We additionally discuss the key discoveries that have been made concerning the role of the AHR in energy metabolism, as well as the current and future directions of the field.

Prevalence and Determinants of Stunting and Thinness/Wasting Among Schoolchildren of Ethiopia: A Systematic Review and Meta-Analysis.

BACKGROUND: Several studies have been carried out assessing the prevalence of undernutrition and possible determinants among schoolchildren in Ethiopia, but there is a lack of systematically gathered and analyzed information. OBJECTIVE: This systematic review and meta-analysis aimed to summarize epidemiological data on undernutrition and possible determinants among schoolchildren in Ethiopia. METHODS: We conducted a systematic review using open access articles that report the prevalence of stunting and wasting/thinness among schoolchildren from PubMed Central, Scopus, and Science direct. The pooled prevalence was determined using a random-effect model while heterogeneities between studies were evaluated by I2 test. RESULTS: A total of 24 716 schoolchildren were included in the 39 eligible articles. The prevalence of stunting and wasting/thinness among schoolchildren in Ethiopia were 23.1% (95% CI: 19.0-27.0) and 22% (95% CI: 17-26), respectively. There was a marked difference in the prevalence of stunting and wasting/thinness across regions of Ethiopia. The risk of stunting was increased with meal frequency ≤3 times a day (odds ratio [OR] = 3.02, 95% CI: 1.90-4.14), age >10 years (OR = 2.16, 95% CI: 1.47-2.85), and family size ≥5 (OR = 1.88, 95% CI: 1.40-2.35). Similarly, the risk of wasting/thinness was increased with male sex (OR = 2.06, 95% CI: 1.54-2.58), low family income (OR = 2.16, 95% CI: 1.30-3.01), and age >10 years (OR = 1.78, 95% CI: 0.74-2.82). CONCLUSION: This study revealed that more than one-fifth of schoolchildren are stunted or wasted/thin in Ethiopia. Large family size, male sex, and student age were consistently associated with stunting and wasting/thinness among schoolchildren. This study highlights the importance of an integrated effort to reduce undernutrition in Ethiopia.