TLR9 in MAFLD and NASH: At the Intersection of Inflammation and Metabolism.

Toll-Like Receptor 9 (TLR9) is an ancient receptor integral to the primordial functions of inflammation and metabolism. TLR9 functions to regulate homeostasis in a healthy system under acute stress. The literature supports that overactivation of TLR9 under the chronic stress of obesity is a critical driver of the pathogenesis of NASH and NASH-associated fibrosis. Research has focused on the core contributions of the parenchymal and non-parenchymal cells in the liver, adipose, and gut compartments. TLR9 is activated by endogenous circulating mitochondrial DNA (mtDNA). Chronically elevated circulating levels of mtDNA, caused by the stress of overnutrition, are observed in obesity, metabolic dysfunction-associated fatty liver disease (MAFLD), and NASH. Clinical evidence is supportive of TLR9 overactivation as a driver of disease. The role of TLR9 in metabolism and energy regulation may have an underappreciated contribution in the pathogenesis of NASH. Antagonism of TLR9 in NASH and NASH-associated fibrosis could be an effective therapeutic strategy to target both the inflammatory and metabolic components of such a complex disease.

Examining Mid-Upper Arm Circumference Malnutrition z-Score Thresholds.

BACKGROUND: Anthropometric z-scores used commonly for diagnosis and determining degree of malnutrition, specifically body mass index (BMIz), weight-for-length (WLz), and mid-upper arm circumference (MUACz), are not wholly concordant, yet the proposed thresholds for classification are identical. This study was designed to critically examine MUACz thresholds and their ability to correctly classify nutrition status. METHODS: This was a 2-year, prospective single-center study of children ≤18 years seen by registered dietitians within a large pediatric institution. The sensitivity, specificity, and predictive performance of the malnutrition classification thresholds were estimated against clinician-based classification. RESULTS: Sixty-one dietitians enrolled 10,401 patients with distributions of z-scores for weight (-0.5 ± 1.9), length (-0.8 ± 1.6), BMI or WL (-0.1 ± 1.8), and MUAC (-0.4 ± 1.5), suggesting participants were smaller and shorter than the reference U.S. POPULATION: Distributions of MUACz were broad and overlapped between nutrition classification groups, an observation that extended to BMIz and WLz as well. Consequently, existing thresholds do not accurately classify 100% of children. Misclassification rates increase, with increasing severity ranging from 8% in children with no malnutrition to 71% in children with severe malnutrition. Algorithm- and manually-based refinement of thresholds result in mixed improvements and can be explored by the reader with the associated supplement. CONCLUSION: The sensitivity of proposed MUACz thresholds systematically decreases with increasing severity of malnutrition and will require optimization if we aim to limit the number of children at risk of misclassification. Indicators for overnutrition remain to be addressed but are explored herein.

Malnutrition in Paediatrics: Stationary Screening & Follow-up.

OBJECTIVE: The prevalence and follow-up of the clinical real-world data focussing on existing or risk of malnutrition in a tertiary hospital general paediatric ward including 4 months of follow-up was assessed. METHODS: Measurements included anthropometric measurements, a nutrition interview and an extended version of the Screening Tool for the Assessment of Malnutrition in Paediatrics (STAMP). R Studio 3.4.2 was used for statistical analysis and diagnosing malnutrition by calculating height-for-age (HfAz)-, weight-for-age (WfAz)- weight-for-height (WfHz)-, body mass index-for-age (BMIz) and mid-upper-arm circumference (MUACz)-z-scores with the childsds package with KIGGS and WHO for reference. RESULTS: The median age of the 68 participants was 8.00 (4.00-13.00) years. The main reasons for hospitalisation in the tertiary centre were gastrointestinal diseases, diabetes mellitus and rheumatic diseases. At admission 39.71%, at the second examination 36.00% and at the third examination 45.90% were malnourished. 68% of inpatients lost weight during their clinical stay, of which 35.29% lost more than 3% of their initial weight. However, changes were not significantly different. CONCLUSION: A significant share of patients was diagnosed to be malnourished at admission, the majority of patients lost weight during their hospital stay and the 4 months after admission. Due to the far reaching consequences for patients, doctors, health insurance and politics, the early diagnosis and treatment of malnutrition should take greater account in the future.

Using Body Composition Assessment to Evaluate the Double Burden of Malnutrition.

BACKGROUND: Populations in low- and middle-income countries are increasingly experiencing a double burden of malnutrition (DBM), incorporating both persistent levels of child undernutrition and rising prevalence of overweight/obesity at later ages. A growing number of individuals experience both components of the DBM through the life-course, thereby accumulating high susceptibility to noncommunicable disease (NCD). SUMMARY: Measurements of body composition may prove valuable for assessing NCD risk at the level of the individual. The capacity-load model provides a simple conceptual framework for integrating data on different components of body composition to predict NCD risk. Poor growth in early life, indexed by becoming wasted or stunted, constrains the development of lean mass components such as muscle and organ mass, each of which contribute to the metabolic capacity for homeostasis. Catch-up weight gain in early life, or the development of excess weight from childhood onwards, is associated with elevated adiposity, especially abdominal adiposity, which challenges cardio-metabolic homeostasis and elevates NCD risk. Key Messages: A variety of techniques are now available for the measurement of body composition, helping research the association of the DBM with NCD risk. Reference charts allow raw data to be converted to age- and sex-specific z-scores, aiding interpretation.

An efficient electrochemiluminescence amplification strategy via bis-co-reaction accelerator for sensitive detection of laminin to monitor overnutrition associated liver damage.

With the world wildly improvement in dietary and nutrition status, it couldn't be ignored that the chronic liver disease (CLD) resulted from the overnutrition. In order to estimate nutrition status for healthy living, an efficient and sensitive electrochemiluminescence (ECL) sandwich immunosensor of laminin (LN), a marker of CLD, was proposed for early diagnosis of CLD. In this work, the anodic ECL behavior of perylene derivative using H2O2 as co-reactant was demonstrated and the possible ECL mechanism was proposed. Furthermore, a significantly amplified ECL response could be obtained via Ag and Fe-Fe2O3 nanoparticles as bis-co-reaction accelerator. As a result, the proposed ECL immunosensor performed good sensitivity and accuracy with a detection limit down to 0.03pg/mL. Moreover, this immunosensor was successfully employed to monitor patient serum, which exhibited an alternative avenue for the early diagnosis of other diseases via proteins, nucleotide sequence, microRNA and cells.

Early life programming and the risk of non-alcoholic fatty liver disease.

Non-alcoholic fatty liver disease (NAFLD) is associated with obesity, insulin resistance, type 2 diabetes and cardiovascular disease and can be considered the hepatic manifestation of the metabolic syndrome. NAFLD represents a spectrum of disease, from the relatively benign simple steatosis to the more serious non-alcoholic steatohepatitis, which can progress to liver cirrhosis, hepatocellular carcinoma and end-stage liver failure, necessitating liver transplantation. Although the increasing prevalence of NAFLD in developed countries has substantial implications for public health, many of the precise mechanisms accounting for the development and progression of NAFLD are unclear. The environment in early life is an important determinant of cardiovascular disease risk in later life and studies suggest this also extends to NAFLD. Here we review data from animal models and human studies which suggest that fetal and early life exposure to maternal under- and overnutrition, excess glucocorticoids and environmental pollutants may confer an increased susceptibility to NAFLD development and progression in offspring and that such effects may be sex-specific. We also consider studies aimed at identifying potential dietary and pharmacological interventions aimed at reducing this risk. We suggest that further human epidemiological studies are needed to ensure that data from animal models are relevant to human health.

Comparación entre personas con malnutrición por exceso, con y sin trastorno por atracón / Comparison between people with overnutrition, with and without binge eating disorder

Introducción: si bien el trastorno por atracón es un trastorno de la conducta alimentaria que no se da exclusivamente en personas obesas, es más común en este grupo que en sujetos con normopeso. Sin embargo, no todas las personas con malnutrición por exceso presentan trastorno por atracón. Objetivo: identificar el conocimiento actual respecto a las diferencias y semejanzas existentes entre personas con malnutrición por exceso, con y sin trastorno por atracón. Método: para lograr el objetivo anterior, se realizó una revisión de artículos científicos en torno al tema. Resultados: primero se analizó la comorbilidad psicopatológica en obesidad y después se detectaron similitudes y diferencias entre los grupos de interés, tanto en sintomatología general, como en sintomatología de la conducta alimentaria. Además, se identificaron algunos aspectos controversiales, en que existe evidencia contradictoria respecto a la comparación intergrupal. Conclusión: de esta revisión se concluye que en el estudio de la obesidad se hace necesario conocer en mayor profundidad las características del subgrupo de pacientes que además presenta trastorno por atracón, ya que estas personas poseen características distintivas cuyo conocimiento permitirá ofrecer tratamientos integrales más adecuados a las necesidades de los pacientes, lo que posibilitará, en consecuencia, diseñar intervenciones más eficaces (AU)

Introduction: Even though binge eating disorder is an eating disorder that does not occur exclusively in obese people, it is more common in this group than in subjects with normal weight. However, it has to be said that not all people with overnutrition have binge eating disorder. Objective: Identify current knowledge about the differences and similarities between people with overnutrition with and without binge eating disorder. Method: A review of scientific articles on the subject was conducted in order to achieve the above mentioned objective. Results: First, psychopathological comorbidity obesity was analyzed and then similarities and differences between the groups of interest were detected, both in general symptoms as well as in symptoms of eating behavior. Furthermore, controversial aspects were found since there is conflicting evidence regarding the intergroup comparison. Conclusion: This review concludes that within the study of obesity it is necessary to know in greater depth the characteristics of the subset of patients who also presents binge eating disorder, because these people have distinctive characteristics that can generate new knowledge that will provide more adequate comprehensive treatment needs of patients, which ultimately will enable to design more effective interventions (AU)

Use of Indirect Calorimetry to Detect Overfeeding in Critically Ill Children: Finding the Appropriate Definition.

OBJECTIVES: Overfeeding during critical illness is associated with adverse effects such as metabolic disturbances and increased risk of infection. Because of the lack of sound studies with clinical endpoints, overfeeding is arbitrarily defined as the ratio caloric intake/measured resting energy expenditure (mREE) or alternatively as a comparison of measured respiratory quotient (RQ) to the predicted RQ based on the macronutrient intake (RQmacr). We aimed to compare definitions of overfeeding in critically ill mechanically ventilated children based on mREE, RQ, and caloric intake to find an appropriate definition. METHODS: Indirect calorimetry measurements were performed in 78 mechanically ventilated children, median age 6.3 months. Enteral and/or parenteral nutrition was provided according to the local guidelines. Definitions used to indicate overfeeding were the ratio caloric intake/mREE of >110% and >120% and by the measured RQ > RQmacr + 0.05. RESULTS: The proportion of patients identified as overfed varied widely depending on the definition used, ranging from 22% (RQ > RQmacr + 0.05), to 40% and 50% (caloric intake/mREE of >120% and >110%, respectively). Linear regression analysis showed that all patients would be identified as overfed with the definition RQ > RQmacr + 0.05 when the ratio caloric intake/mREE exceeded 165%. Caloric intake was higher in children with a standard deviation-score weight for age <-2. CONCLUSIONS: The proportion of mechanically ventilated patients identified as overfed ranged widely depending on the definition applied. These currently used definitions fail to take into account several relevant factors affecting metabolism during critical illness and are therefore not generally applicable to the pediatric intensive care unit population.

Under-reporting of dietary energy intake in five populations of the African diaspora.

Studies on the role of diet in the development of chronic diseases often rely on self-report surveys of dietary intake. Unfortunately, many validity studies have demonstrated that self-reported dietary intake is subject to systematic under-reporting, although the vast majority of such studies have been conducted in industrialised countries. The aim of the present study was to investigate whether or not systematic reporting error exists among the individuals of African ancestry (n 324) in five countries distributed across the Human Development Index (HDI) scale, a UN statistic devised to rank countries on non-income factors plus economic indicators. Using two 24 h dietary recalls to assess energy intake and the doubly labelled water method to assess total energy expenditure, we calculated the difference between these two values ((self-report - expenditure/expenditure) × 100) to identify under-reporting of habitual energy intake in selected communities in Ghana, South Africa, Seychelles, Jamaica and the USA. Under-reporting of habitual energy intake was observed in all the five countries. The South African cohort exhibited the highest mean under-reporting ( - 52·1% of energy) compared with the cohorts of Ghana ( - 22·5%), Jamaica ( - 17·9%), Seychelles ( - 25·0%) and the USA ( - 18·5%). BMI was the most consistent predictor of under-reporting compared with other predictors. In conclusion, there is substantial under-reporting of dietary energy intake in populations across the whole range of the HDI, and this systematic reporting error increases according to the BMI of an individual.

Metabolic remodelling in obesity and type 2 diabetes: pathological or protective mechanisms in response to nutrient excess?

Altered metabolism in tissues such as the liver, skeletal muscle and adipose tissue is observed in metabolic diseases characterized by nutrient excess and energy imbalance, such as obesity and type 2 diabetes. These alterations in metabolism can include resistance to the hormone insulin, lipid accumulation, mitochondrial dysfunction and transcriptional remodelling of major metabolic pathways. The underlying assumption has been that these same alterations in metabolism are fundamental to the pathogenesis of metabolic diseases. An alternative view is that these alterations in metabolism occur to protect cell and tissue viability in the face of constant positive energy balance. This speculative review presents evidence that many of the metabolic adaptations that occur in metabolic diseases characterized by nutrient excess can be viewed as protective in nature, rather than pathogenic per se for disease progression. Finally, we also briefly discuss the usefulness and potential pitfalls of therapeutic approaches that attempt to correct these same metabolic defects when energy balance is not altered, and the potential links between metabolic survival responses and other chronic diseases such as cancer.

Diet and esophageal disease.

The following, from the 12th OESO World Conference: Cancers of the Esophagus, includes commentaries on macronutrients, dietary patterns, and risk of adenocarcinoma in Barrett's esophagus; micronutrients, trace elements, and risk of Barrett's esophagus and esophageal adenocarcinoma; the role of mate consumption in the development of squamous cell carcinoma; the relationship between energy excess and development of esophageal adenocarcinoma; and the nutritional management of the esophageal cancer patient.

Leptin levels at birth and infant growth: the EPOCH study.

OBJECTIVE: To examine the association of cord blood leptin with body mass index (BMI) growth velocity from birth to 12 months of age among infants exposed and not exposed to over-nutrition in utero (defined as maternal overweight/obesity or presence of gestational diabetes). METHODS: 185 infants enrolled in the Exploring Perinatal Outcomes among Children study (76 exposed and 109 not exposed) had leptin and insulin measured in cord blood. Longitudinal weight and length measures in the first 12 months of life (average 4 per participant) obtained from medical records were used to compute BMI growth rates. Mixed models were used to examine associations of cord blood leptin with growth. RESULTS: Compared with unexposed infants, those exposed had significantly higher cord blood insulin (8.64 v. 6.97 uU/ml, P<0.01) and leptin levels (8.89 v. 5.92 ng/ml, P=0.05) as well as increased birth weights (3438.04 v. 3306.89 g, P=0.04). There was an inverse relationship between cord leptin levels and BMI growth from birth to 12 months of age (P=0.005); however, exposure to over-nutrition in utero did not significantly modify this association (P=0.59). CONCLUSION: We provide support of a possible operational feedback mechanism by which lower cord blood leptin levels are associated with faster infant growth in the first year of life. Our data do not tend to support the hypothesis that this mechanism is altered in infants exposed to over-nutrition in utero; however our sample is too small to provide sufficient evidence. Larger epidemiological studies are needed to elucidate the mechanisms responsible for increased propensity for obesity in exposed offspring.

Risk of malnutrition (over and under-nutrition): validation of the JaNuS screening tool.

BACKGROUND & AIMS: Malnutrition (over and under-nutrition) is highly prevalent in patients admitted to hospital and it is a well-known risk factor for increased morbidity and mortality. Nutritional problems are often misdiagnosed, and especially the coexistence of over and undernutrition is not usually recognized. We aimed to develop and validate a screening tool for the easy detection and reporting of both undernutrition and overnutrition, specifically identifying the clinical conditions where the two types of malnutrition coexist. METHODS: The study consisted of three phases: 1) selection of an appropriate study population (estimation sample) and of the hospital admission parameters to identify overnutrition and undernutrition; 2) combination of selected variables to create a screening tool to assess the nutritional risk in case of undernutrition, overnutrition, or the copresence of both the conditions, to be used by non-specialist health care professionals; 3) validation of the screening tool in a different patient sample (validation sample). RESULTS: Two groups of variables (12 for undernutrition, 7 for overnutrition) were identified in separate logistic models for their correlation with the outcome variables. Both models showed high efficacy, sensitivity and specificity (overnutrition, 97.7%, 99.6%, 66.6%, respectively; undernutrition, 84.4%, 83.6%, 84.8%). The logistic models were used to construct a two-faced test (named JaNuS - Just A Nutritional Screening) fitting into a two-dimension Cartesian coordinate graphic system. In the validation sample the JaNuS test confirmed its predictive value. Internal consistency and test-retest analysis provide evidence for the reliability of the test. CONCLUSION: The study provides a screening tool for the assessment of the nutritional risk, based on parameters easy-to-use by health care personnel lacking nutritional competence and characterized by excellent predictive validity. The test might be confidently applied in the clinical setting to determine the importance of malnutrition (including the copresence of over and undernutrition) as a risk factor for morbidity and mortality.

Benefits and constraints in screening for non-communicable diseases in the rural area of Thailand's northeast.

OBJECTIVE: To investigate the benefits and constraints of a screening attempt as initiated by the Ministry of Public Health (MoPH) measuring over-nutrition, hypertension and type 2 diabetes mellitus (T2DM) undertaken by the local health officials on sub-district level. MATERIAL AND METHOD: Capillary blood glucose (CBG), body mass index (BMI), blood pressure, and history of type 2 diabetes mellitus (T2DM) of first degree relatives was assessed following the direction of the Ministry of Public Health (MoPH) by the local health officials. RESULTS: The proportions of obesity, hypertension, and T2DM from 7,698 villagers were about 35%, 20%, and suspected to be 9%, respectively. This was similar to previous investigations except for the history of T2DM of first-degree relatives, which strongly relates to elevated CBG levels. A high percentage of missing value was recognized for all variables. CONCLUSION: The screening of non-communicable disease program executed by the lower level of the health delivery system is an achievement by itself It can detect new cases of diseases. However incompleteness of variables is a constraint observed due to high workload of the health staff To decrease the burden of the public health staff and the curative sector and increase accuracy, the proportion of the population eligible for screening should be restricted to a higher age, being obese, and having a first-degree relative with diabetes mellitus.

The relationship between nutrition and prostate cancer: is more always better?

CONTEXT: Prostate cancer (PCa) remains one of the most diagnosed malignancies in the world, correlating with regions where men consume more of a so-called Western-style diet. As such, there is much interest in understanding the role of lifestyle and diet on the incidence and progression of PCa. OBJECTIVE: To provide a summary of published literature with regard to dietary macro- and micronutrients and PCa incidence and progression. EVIDENCE ACQUISITION: A literature search was completed using the PubMed database for all studies published on diet and PCa in June 2012 or earlier. Primary literature and meta-analyses were given preference over other review articles when possible. EVIDENCE SYNTHESIS: The literature was reviewed on seven dietary components: carbohydrates, protein, fat and cholesterol, vegetables, vitamins and minerals, and phytochemicals. Current literature linking these nutrients to PCa is limited at best, but trends in the published data suggest consumption of carbohydrates, saturated and ω-6 fats, and certain vitamin supplements may promote PCa risk and progression. Conversely, consumption of many plant phytochemicals and ω-3 fatty acids seem to slow the risk and progression of the disease. All other nutrients seem to have no effect or data are inconclusive. A brief summary about the clinical implications of dietary interventions with respect to PCa prevention, treatment, and survivorship is provided. CONCLUSIONS: Due to the number and heterogeneity of published studies investigating diet and PCa, it is difficult to determine what nutrients make up the perfect diet for the primary and secondary prevention of PCa. Because diets are made of multiple macro- and micronutrients, further prospective studies are warranted, particularly those investigating the relationship between whole foods instead of a single nutritional component.

The evaluation of body composition: a useful tool for clinical practice.

Undernutrition is insufficiently detected in in- and outpatients, and this is likely to worsen during the next decades. The increased prevalence of obesity together with chronic illnesses associated with fat-free mass (FFM) loss will result in an increased prevalence of sarcopenic obesity. In patients with sarcopenic obesity, weight loss and the body mass index lack accuracy to detect FFM loss. FFM loss is related to increasing mortality, worse clinical outcomes, and impaired quality of life. In sarcopenic obesity and chronic diseases, body composition measurement with dual-energy X-ray absorptiometry, bioelectrical impedance analysis, or computerized tomography quantifies the loss of FFM. It allows tailored nutritional support and disease-specific therapy and reduces the risk of drug toxicity. Body composition evaluation should be integrated into routine clinical practice for the initial assessment and sequential follow-up of nutritional status. It could allow objective, systematic, and early screening of undernutrition and promote the rational and early initiation of optimal nutritional support, thereby contributing to reducing malnutrition-induced morbidity, mortality, worsening of the quality of life, and global health care costs.

Growth assessment in clinical practice: whose growth curve?

Differences in growth curves can influence the diagnosis of under- and overnutrition, and the interpretation of adequate growth following nutrition intervention. This effect is notable when comparing the World Health Organization (WHO) 2006 Growth Standard and the Centers for Disease Control and Prevention (CDC) 2000 Growth Reference for infants and children to 59 months of age. Important differences relate to conceptual approaches for generating growth standards to describe what population growth should be, compared to a reference of what growth is. WHO included only term infants exclusively or predominantly breast-fed beyond 4 months, and data for infants and children indicative of excess adiposity and growth failure were removed. Thus, fewer children are diagnosed with poor weight gain, and more with excess adiposity, using the WHO Growth Standard than when using the CDC Growth Reference. Adequate growth is based on proportional height and weight gains that track along growth curve trajectories. Use of the WHO curves should assist in prevention of inappropriate intervention or overfeeding in young children.

Usefulness of the Mini Nutritional Assessment (MNA) in predicting the nutritional status of people with mental disorders in Taiwan.

OBJECTIVE: The study was to evaluate the ability of the Mini Nutritional Assessment in predicting malnutrition in people with three subtypes of mental disorder (schizophrenia, major depression and bipolar disorder) in Taiwan. DESIGN: The study involved a convenience sample of 120 residents of psychiatric wards managed by a hospital in central Taiwan (52 with schizophrenia, 36 with major depression and 32 with bipolar disorder) classified according to the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition criteria. METHODS: A structured questionnaire elicited subjects' personal data, disease history and answers to questions in the Mini Nutritional Assessment. Serum and anthropometrical parameters were measured. Nutritional status was evaluated with a content-equivalent version of the Mini Nutritional Assessment (Taiwan version-1, T1). RESULTS: The Mini Nutritional Assessment-Taiwan version-1 was effective in assessing the nutritional status of people of all three subtypes of disorder. Nutritional statuses predicted with the Mini Nutritional Assessment-Taiwan version-1 agreed well with other nutritional indicators such as BMI, waist circumference and appetite status. According to the Mini Nutritional Assessment-Taiwan version-1, people with major depression were more likely to be at risk of undernutrition, whereas people with schizophrenia or bipolar disorder were more likely to be at risk of overnutrition. CONCLUSION: The Mini Nutritional Assessment-Taiwan version-1 can effectively grade both undernutrition and overnutrition of people with schizophrenia, major depression or bipolar disorder. RELEVANCE TO CLINICAL PRACTICE: The Mini Nutritional Assessment enables nurses to monitor emerging nutritional problems in people with psychiatric disorder without relying on subjective judgement. With proper intervention, it can help reduce nutrition-related chronic conditions in these individuals and save on healthcare cost.

Adipokines as novel biomarkers and regulators of the metabolic syndrome.

Over the past two decades our view of adipose tissue has undergone a dramatic change from an inert energy storage tissue to an active endocrine organ. Adipose tissue communicates with other central and peripheral organs by synthesis and secretion of a host of molecules that we generally refer to as adipokines. The levels of some adipokines correlate with specific metabolic states and have the potential to impact directly upon the metabolic homeostasis of the system. A dysregulation of adipokines has been implicated in obesity, type 2 diabetes, hypertension, cardiovascular disease, and an ever-growing larger list of pathological changes in a number of organs. Here, we review the recent progress regarding the synthesis, secretion, and physiological function of adipokines with perspectives on future directions and potential therapeutic goals.