Patients with PWS and related syndromes display differentially methylated regions involved in neurodevelopmental and nutritional trajectory.

BACKGROUND: Prader-Willi syndrome is a rare genetic neurodevelopmental disorder caused by a paternal deficiency of maternally imprinted gene expression located in the chromosome 15q11-q13 region. Previous studies have demonstrated that several classes of neurodevelopmental disorders can be attributed to either over- or under-expression of specific genes that may lead to impairments in neuronal generation, differentiation, maturation and growth. Epigenetic changes that modify gene expression have been highlighted in these disorders. One recent study focused on epigenetic analysis and compared patients with PWS with patients with other imprinting disorders. No study, however, has yet focused on epigenetics in patients with PWS specifically by comparing the mutations associated with this syndrome. OBJECTIVE: This study investigated the epigenetic modifications in patients with PWS and patients with PWS-related disorders caused by inactivation of two genes of the PWS chromosomal region, SNORD116 and MAGEL2. Our approach also aimed to compare the epigenetic modifications in PWS and PWS-related disorders. METHODS: We compared genome-wide methylation analysis (GWAS) in seven blood samples from patients with PWS phenotype (five with deletions of the PWS locus, one with a microdeletion of SNORD116 and one with a frameshift mutation of MAGEL2 presenting with Schaaf-Yang syndrome), as well as two control patients. Controls were infants that had been studied for suspicion of genetic diseases that was not confirmed by the genetic analysis and the clinical follow-up. RESULTS: The analysis identified 29,234 differentially methylated cytosines, corresponding to 5,308 differentially methylated regions (DMRs), which matched with 2,280 genes. The DMRs in patients with PWS were associated with neurodevelopmental pathways, endocrine dysfunction and social and addictive processes consistent with the key features of the PWS phenotype. In addition, the separate analysis for the SNORD116 and MAGEL2 deletions revealed that the DMRs associated with the SNORD116 microdeletion were found in genes implicated in metabolic pathways and nervous system development, whereas MAGEL2 mutations mostly concerned genes involved in macromolecule biosynthesis. CONCLUSION: The PWS is associated with epigenetic modifications with differences in SNORD116 and MAGEL2 mutations, which seem to be relevant to the different associated phenotypes.

Chronic Nutrition Impact Symptoms Are Associated with Decreased Functional Status, Quality of Life, and Diet Quality in a Pilot Study of Long-Term Post-Radiation Head and Neck Cancer Survivors.

BACKGROUND: As a result of tumor location and treatment that is aggressive, head and neck cancer (HNC) survivors experience an array of symptoms impacting the ability and desire to eat termed nutrition impact symptoms (NISs). Despite increasing cancer survival time, the majority of research studies examining the impact of NISs have been based on clinical samples of HNC patients during the acute phase of treatment. NISs are often chronic and persist beyond the completion of treatment or may develop as late side effects. Therefore, our research team examined chronic NIS complications on HNC survivors' functional status, quality of life, and diet quality. METHODS: This was a cross-sectional study of 42 HNC survivors who were at least 6 months post-radiation. Self-reported data on demographics, NISs, quality of life, and usual diet over the past year were obtained. Objective measures of functional status included the short physical performance battery and InBody© 270 body composition testing. NISs were coded so a lower score indicated lower symptom burden, (range 4-17) and dichotomized as ≤10 vs. >10, the median in the dataset. Wilcoxon rank sum tests were performed between the dichotomized NIS summary score and continuous quality of life and functional status outcomes. Diet quality for HNC survivors was calculated using the Healthy Eating Index 2015 (HEI-2015). Wilcoxon rank sum tests examined the difference between the HNC HEI-2015 as compared to the National Health and Nutrition Examination Survey (NHANES) data calculated using the population ratio method. RESULTS: A lower NIS score was statistically associated with higher posttreatment lean muscle mass (p = 0.002). A lower NIS score was associated with higher functional (p = 0.0006), physical (p = 0.0007), emotional (p = 0.007), and total (p < 0.0001) quality of life. Compared to NHANES controls, HNC survivors reported a significantly lower HEI-2015 diet quality score (p = 0.0001). CONCLUSIONS: Lower NIS burden was associated with higher lean muscle mass and functional, physical, emotional, and total quality of life in post-radiation HNC survivors. HNC survivors reported a significantly lower total HEI-2015 as compared to healthy NHANES controls, providing support for the hypothesis that chronic NIS burden impacts the desire and ability to eat. The effects of this pilot study were strong enough to be detected by straight forward statistical approaches and warrant a larger longitudinal study. For survivors most impacted by NIS burden, multidisciplinary post-radiation exercise and nutrition-based interventions to manage NISs and improve functional status, quality of life, and diet quality in this survivor population are needed.

Sleep disorders related to nutrition and digestive diseases: a neglected clinical condition.

Sleep disturbances often result from inappropriate lifestyles, incorrect dietary habits, and/or digestive diseases. This clinical condition, however, has not been sufficiently explored in this area. Several studies have linked the circadian timing system to the physiology of metabolism control mechanisms, energy balance regulation, and nutrition. Sleep disturbances supposedly trigger digestive disorders or conversely represent specific clinical manifestation of gastrointestinal (GI) diseases. Poor sleep may worsen the symptoms of GI disorders, affecting the quality of life. Conversely, short sleep may influence dietary choices, as well as meal timing, and the circadian system drives temporal changes in metabolic patterns. Emerging evidence suggests that patients with inappropriate dietary habits and chronic digestive disorders often sleep less and show lower sleep efficiency, compared with healthy individuals. Sleep disturbances may thus represent a primary symptom of digestive diseases. Further controlled trials are needed to fully understand the relationship between sleep disturbances, dietary habits, and GI disorders. It may be also anticipated that the evaluation of sleep quality may prove useful to drive positive interventions and improve the quality of life in a proportion of patients. This review summarizes data linking sleep disorders with diet and a series of disease including gastro-esophageal reflux disease, peptic disease, functional gastrointestinal disorders, inflammatory bowel diseases, gut microbiota alterations, liver and pancreatic diseases, and obesity. The evidence supporting the complex interplay between sleep dysfunction, nutrition, and digestive diseases is discussed.

Obesity and Other Nutrition Related Abnormalities in Pre-Dialysis Chronic Kidney Disease (CKD) Participants.

Chronic kidney disease (CKD) is increasing in sub-Saharan Africa. Undernutrition has been prevalent amongst end stage CKD patients, with limited data on the prevalence of obesity. The aim of this study was to assess the nutritional status of CKD patients using various methods sensitive to over and under-nutrition. Stage 3 to 5 CKD patients (glomerular filtration rate (GFR) < 60 mL/min/1.73 m2) attending a pre-dialysis clinic in Cape Town, were enrolled. Exclusion criteria included infectious and autoimmune conditions. Sociodemographic, clinical and biochemical data were collected, and anthropometric measurements were performed. Dietary intake was measured with a quantified food frequency questionnaire (FFQ). Statistical Package for the Social Sciences (SPSS) version 26 was used for statistical analysis. Seventy participants, with mean age of 41.8 ± 11.8 years, 52.9% females and 47.1% males were enrolled. Participants enrolled mainly had stage 5 kidney failure. Thirty percent were overweight (21) and 25 (36%) were obese, 22 (60%) of females were overweight and obese, while 13 (39.4%) of males were predominantly normal weight. Abdominal obesity was found in 42 (60%) of participants, mainly in females. Undernutrition prevalence was low at 3%. Dietary assessment showed a high sugar and protein intake. There was a high prevalence of overweight, obesity and abdominal obesity in CKD stage 35 patients, with unhealthy dietary intake and other nutritional abnormalities.

Abnormal FDG Uptake on PET/CT Due to Periosteal Reaction Caused by Hypervitaminosis D in a Pediatric Patient.

A 7-year-old boy presented with diffuse bone pain. FDG PET/CT was performed to find the possible underlying malignant cause of hypercalcemia. The images demonstrated multiple foci of abnormal FDG activity at the sites of periosteal reaction. In addition, calcium deposit was noted in the basal ganglia, stomach, and the colon. History taking revealed that the patient had routinely taken an over-the-counter "supplement" that contains a high dose of vitamin D. One week after calcitonin therapy and stopping the supplement, the patient became symptom free. This case suggests that hypervitaminosis D might cause hypermetabolic periosteal reaction on FDG PET/CT imaging.

The Effect of Comorbidities on Wound Healing.

Wound healing is affected by several factors. Preexisting diagnoses may significantly alter, delay, or inhibit normal wound healing. This is most commonly seen with chronic disorders, such as diabetes and renal failure, but also occurs secondary to aging and substance abuse. Less commonly, genetic or inflammatory disorders are the cause of delayed wound healing. In some cases, it is not the illness, but the treatment that can inhibit wound healing. This is seen in patients getting chemotherapy, radiation, steroids, methotrexate, and a host of other medications. Understanding these processes may help treat or avoid wound healing problems.

Association of unhealthy dietary behaviors with renal function decline in patients with diabetes.

OBJECTIVE: Balanced nutrition is important for patients with diabetes, and nutrition might well influence diabetes-related complications, although there is limited evidence for this supposition at present. Consequently, we investigate the association between dietary behaviors and renal function decline among patients with diabetes. RESEARCH DESIGN AND METHODS: From 2011 to 2013, a total of 2797 patients with type 2 diabetes participated in the Diabetes Shared Care Program at Chang Gung Memorial Hospital. All received nutritional consulting by dieticians and an eight-item list of unhealthy dietary behaviors, which included the excessive intake of carbohydrates, fats, protein, fruit, pickled foods, dessert and alcohol, as well as inadequate dietary vegetable. Estimated glomerular filtration rate (eGFR) decline ≥40% was defined as a surrogate end point for kidney damage. Independent dietary risk factors predicting poor renal outcomes were assessed. RESULTS: Stable mean glycated hemoglobin (A1c) (7.78% to 7.75%, p=0.151), improved cholesterol (174.04 to 170.13 mg/dL, p<0.001) and low-density lipoprotein (104.19 to 98.07 mg/dL, p<0.001) were found in patients throughout 2 years of therapy. However, significant eGFR decline was noted (94.20 to 88.08 mL/min/1.73 m2, p<0.001). A total of 125 subjects had eGFR decline ≥40% and 2672 had stable renal progression.In regression analysis, 625 stable renal patients (selected via propensity score matching) and 125 subjects with eGFR decline ≥40% demonstrated excessive pickled foods to be predictive of poor renal outcomes (OR 1.861, 95% CI 1.230 to 2.814, p=0.003). CONCLUSIONS: Our study suggests that excessive pickled foods deteriorate renal function more than other unhealthy dietary behaviors in patients with diabetes.

Associations of age and body mass index with hydration and density of fat-free mass from 4 to 22 years.

BACKGROUND: Most body composition techniques assume constant properties of fat free mass (FFM) (hydration and density) regardless of nutritional status, which may lead to biased values. AIM: To evaluate the interactive associations of age and body mass index (BMI) with hydration and density of FFM. METHODS: Data from subjects aged between 4 and 22 years old from several studies conducted in London, UK were assessed. Hydration (HFFM) and density (DFFM) of FFM obtained from the four-component model in 936 and 905 individuals, respectively, were assessed. BMI was converted in to z-scores, and categorised into five groups using z-score cut-offs (thin, normal weight, overweight, obese, and severely obese). Linear regression models for HFFM and DFFM were developed using age, sex, and BMI group as predictors. RESULTS: Nearly 30% of the variability in HFFM was explained by models including age and BMI groups, showing increasing HFFM values in heavier BMI groups. On the other hand, ∼40% of variability in DFFM was explained by age, sex, and BMI groups, with DFFM values decreasing in association with higher BMI group. CONCLUSION: Nutritional status should be considered when assessing body composition using two-component methods, and reference data for HFFM and DFFM is needed for higher BMI groups to avoid bias. Further research is needed to explain intra-individual variability in FFM properties.

Nutritional management in renal transplant recipients: A transplant team opportunity to improve graft survival.

AIMS: The nutritional management of renal transplant recipients (RTR) represents a complex problem either because the recovery of renal function is not complete and for the appearance of "unavoidable" metabolic side effects of immunosuppressive drugs. Nevertheless, it remains a neglected problem, whereas an appropriate dietary intervention could favorably affect graft survival. DATA SYNTHESIS: Renal transplantation is associated with steroids and calcineurin inhibitors administration, liberalization of diet after dialysis restrictions, and patients' better quality of life. These factors predispose, from the first months after surgery, to body weight gain, enhanced post transplant diabetes, hyperlipidemia, metabolic syndrome, with negative consequences on graft outcome. Unfortunately, specific guidelines about this topic and nutritional counseling are scarce; moreover, beyond the low adherence of patients to any dietary plan, there is a dangerous underestimation of the problem by physicians, sometimes with inadequate interventions. A prompt and specific nutritional management of RTR can help prevent or minimize these metabolic alterations, mostly when associated with careful and repeated counseling. CONCLUSIONS: A correct nutritional management, possibly tailored to enhance patients' motivation and adherence, represents the best preventive maneuver to increase patients' life and probably improve graft survival, at no cost and with no side effects.

Nutrition status in patients with wounds: a cross-sectional analysis of 50 patients with chronic leg ulcers or acute wounds.

BACKGROUND: The possible impact of nutritional status on healing and course of disease in patients with chronic wounds is widely suggested, however, most data are based on small groups of patients with no control group and minor afflictions. Clear diagnostic strategies are missing. OBJECTIVES: To analyse in detail the nutritional status of chronic wound patients relative to healthy controls based on a large patient population. MATERIAL AND METHODS: We screened a group of 50 patients for their nutritional status based on body mass index (BMI), the Mini-Nutritional Assessment (MNA), and Nutritional Risk Screening (NRS), as well as additional laboratory investigations. Twenty-five patients suffered from chronic venous leg ulcers and were compared with a matching control group of 25 patients with acute surgical wounds. RESULTS: Patients with chronic venous leg ulcers showed significantly higher BMI, hyperhomocysteinaemia, and higher levels of serum copper but significantly lower levels of vitamin B6, B9 and C, as well as a significantly lower level of zinc. Vitamin D deficiency was present in both groups, however, severe vitamin D deficiency was present only in the leg ulcer group. Mobility was significantly reduced in patients with leg ulcers. CONCLUSION: Ulcer patients are often obese but suffer from qualitative malnutrition, including a lack of vitamin D, which might be explained by reduced mobility and being housebound. Hypoalbuminaemia, as a sign of protein deficiency, was observed significantly more often in patients with chronic leg ulcers, irrespective of wound area or wound duration.

Growth patterns of Palestinian children from birth to 24 months.

BACKGROUND: Growth faltering in early life can adversely affect health in later childhood and adulthood. Growth monitoring of children can provide evidence to help formulate effective strategies to address growth problems but such information on Palestinian children is lacking. OBJECTIVES: This study aimed to determine the growth patterns of children under 2 years in Gaza, Palestine. METHODS: This retrospective cohort study was conducted in 2014 in 10 randomly selected primary health care clinics in 5 governorates of Gaza. Weight and length data were obtained from the health cards of children born in 2012, and z-scores were calculated and compared with the WHO Growth Standard (2006). RESULTS: A total of 2 632 children's cards were included at the beginning of the study. Weight-for-age and weight-forlength decreased from birth to 6 months to about -0.40 SD but increased afterwards to -0.11 SD and 0.34 SD at 24 months respectively. Length-for-age declined after 6 months, reaching -0.85 SD at 24 months. At 6 months, the prevalence of underweight and stunting were 5% and 9% but at 24 months, the prevalence was 4% and 20% respectively. Wasting was highest at 6 months (10%) but decreased to 3% at 24 months. Significantly more girls were stunted at 9, 12 and 18 months (P < 0.001), underweight at 24 months (P < 0.05) and wasted at 12 months (P < 0.05). Early life faltering in length was more pronounced than weight, with stunting occurring in one fifth of boys and girls by 2 years of age. CONCLUSIONS: Preventive strategies are urgently needed to address early life causes of undernutrition, particularly stunting, in Palestinian children in Gaza.

Emerging concepts on the role of epigenetics in the relationships between nutrition and health.

Understanding the physiological and metabolic underpinnings that confer individual differences in responses to diet and diet-related chronic disease is essential to advance the field of nutrition. This includes elucidating the differences in gene expression that are mediated through programming of the genome through epigenetic chromatin modifications. Epigenetic landscapes are influenced by age, genetics, toxins and other environmental factors, including dietary exposures and nutritional status. Epigenetic modifications influence transcription and genome stability are established during development with life-long consequences. They can be inherited from one generation to the next. The covalent modifications of chromatin, which include methylation and acetylation, on DNA nucleotide bases, histone proteins and RNA are derived from intermediates of one-carbon metabolism and central metabolism. They influence key physiological processes throughout life, and together with inherited DNA primary sequence, contribute to responsiveness to environmental stresses, diet and risk for age-related chronic disease. Revealing diet-epigenetic relationships has the potential to transform nutrition science by increasing our fundamental understanding of: (i) the role of nutrients in biological systems, (ii) the resilience of living organisms in responding to environmental perturbations, and (iii) the development of dietary patterns that programme physiology for life-long health. Epigenetics may also enable the classification of individuals with chronic disease for specific dietary management and/or for efficacious diet-pharmaceutical combination therapies. These new emerging concepts at the interface of nutrition and epigenetics were discussed, and future research needs identified by leading experts at the 26th Marabou Symposium entitled 'Nutrition, Epigenetics, Genetics: Impact on Health and Disease'. For a compilation of the general discussion at the marabou symposium, click here http://www.marabousymposium.org/.

Causes of low peak bone mass in women.

Peak bone mass is the maximum bone mass that accrues during growth and development. Consolidation of peak bone mass normally occurs during early adulthood. Low peak bone mass results from failure to achieve peak bone mass genetic potential, primarily due to bone loss caused by a variety of conditions or processes occurring at younger ages than usual. Recognized causes of low peak bone mass include genetic causes, endocrine disorders, nutritional disorders, chronic diseases of childhood or adolescence, medications, and idiopathic factors.

Keystones affecting sub-Saharan Africa's prospects for achieving food security through balanced diets.

Socio-economic dynamics determine the transition from diets characterized by the risk of famine, to those characterized by the risk of diet-related non-communicable disease (DR-NCD). This transition is of particular concern in Sub-Saharan Africa (SSA) in which key socio-economic interactions that influence diet include economic growth and rapid urbanization; inequality and a growing middle class; and obesogenic food environments and an increasing prevalence of DR-NCD. In each case, countries in SSA are among those experiencing the most rapid change in the world. These interactions, styled as 'keystones', affect the functioning of other components of the food system and the diets that result. Data from the wealthiest quartile of countries in SSA suggest that these keystones may be increasing the risk of DR-NCD, widening inequalities in health outcomes due to unbalanced diets. To address this, new consumer and government capabilities that address these keystones are required. Food sensitive urban planning, supporting food literacy and fiscal management of consumption are examples.

Considerations for Secondary Prevention of Nutritional Deficiencies in High-Risk Groups in High-Income Countries.

Surveys in high-income countries show that inadequacies and deficiencies can be common for some nutrients, particularly in vulnerable subgroups of the population. Inadequate intakes, high requirements for rapid growth and development, or age- or disease-related impairments in nutrient intake, digestion, absorption, or increased nutrient losses can lead to micronutrient deficiencies. The consequent subclinical conditions are difficult to recognize if not screened for and often go unnoticed. Nutrient deficiencies can be persistent despite primary nutrition interventions that are aimed at improving dietary intakes. Secondary prevention that targets groups at high risk of inadequacy or deficiency, such as in the primary care setting, can be a useful complementary approach to address persistent nutritional gaps. However, this strategy is often underestimated and overlooked as potentially cost-effective means to prevent future health care costs and to improve the health and quality of life of individuals. In this paper, the authors discuss key appraisal criteria to consider when evaluating the benefits and disadvantages of a secondary prevention of nutrient deficiencies through screening.

Can adverse effects of excessive vitamin D supplementation occur without developing hypervitaminosis D?

Vitamin D is a fat-soluble hormone that has endocrine, paracrine and autocrine functions. Consumption of vitamin D-supplemented food & drugs have increased significantly in the last couple of decades due to campaign and awareness programs. Despite such wide use of artificial vitamin D supplements, serum level of 25 hydroxyvitamin D does not always reflect the amount of uptake. In contrast to the safe sunlight exposure, prolonged and disproportionate consumption of vitamin D supplements may lead to vitamin D intoxication, even without developing hypervitaminosis D. One of the reasons why vitamin D supplementation is believed to be safe is, it rarely raises serum vitamin D levels to the toxic range even after repeated intravenous ingestion of extremely high doses of synthetic vitamin D analogs. However, prolonged consumption of vitamin D supplementation may induce hypercalcemia, hypercalciuria and hyperphosphatemia, which are considered to be the initial signs of vitamin D intoxication. It is likely that calcium and phosphorus dysregulation, induced by exogenous vitamin D supplementation, may lead to tissue and organ damages, even without developing hypervitaminosis D. It is needed to be emphasized that, because of tight homeostatic control of calcium and phosphorus, when hypercalcemia and/or hyperphosphatemia is apparent following vitamin D supplementation, the process of tissue and/or organ damage might already have been started.