Malnutrition, nutritional deficiency and alcohol: A guide for general practice.

BACKGROUND: Alcohol use has an effect on nutritional status, with nutritional deficiencies being a major contributor to morbidity, for example Wernicke's encephalopathy. Currently, there is an absence of best-practice guidelines to support general practitioners (GPs) in the identification and management of malnutrition and nutritional risk factors in patients who drink at risky levels. OBJECTIVE: This article reviews some of the nutritional considerations in patients who drink at risky levels or who have alcohol dependence, with the aim of enhancing GPs' awareness of the nutritional considerations in this patient group. DISCUSSION: Nutritional risk factors extend beyond body mass index (BMI), and patients might present with a healthy BMI and be malnourished. Screening for risk of malnutrition and other nutritional deficiencies followed by supplementation and consideration of referral to multidisciplinary services, including a dietitian, is likely to improve patient outcomes.

The Association of Frailty and Malnutrition With Dietary Intake and Gastrointestinal Symptoms in People With Kidney Failure: 2-Year Prospective Study.

BACKGROUND: Frailty and malnutrition are both associated with worsening morbidity and mortality and become more prevalent in the elderly and as kidney function declines. Anorexia and reduced oral intake are common features of both frailty and malnutrition. However, there are sparse data evaluating the impact of other gastrointestinal (GI) symptoms, such as taste changes, on rates of frailty and malnutrition in people with kidney failure. The aim of this study is to describe the prevalence of frailty and malnutrition and their association with dietary intake and nutrition-related symptoms in people with kidney failure. METHODS: This observational study recruited people with kidney failure who were commencing Conservative Kidney Management or elderly people (aged > 75 years) newly commenced on dialysis from 3 renal units. Participants underwent assessments of frailty, nutritional status, dietary intake, and GI symptom burden when they attended clinic appointments, approximately every 6 months. RESULTS: Of the 85 participants, 57% were assessed as being frail and 33% were assessed as being malnourished. Participants assessed as frail reported more GI symptoms (3 vs. 2, P < .001) that were more severe (1.75 vs. 1.0, P < .001) compared to nonfrail participants. Being malnourished was associated with a 5 times higher chance of being frail (odds ratio 5.8; 95% confidence interval 1.5, 21.8; P = .015) and having more severe symptoms was associated with a 2 times higher chance (odds ratio 2.8; 95% CI 1.1, 7.0; P = .026) of being frail. In addition to experiencing more GI symptoms, that were more severe, participants who were malnourished consumed significantly less energy (1234 kcal vs. 1400 kcal, P = .01) and protein (51 g vs. 74 g, P < .001). CONCLUSIONS: Frailty and malnutrition are common and are associated with a higher GI symptom burden and poorer dietary intake. Future research is needed to determine effective interventions targeting frailty and malnutrition, including nutrition-related symptoms and optimal protein intake.

A filter-rectify-filter model of the tactile perception of 3D-printed, texture-defined form.

We show that a two-stage filter-rectify-filter (FRF) model, previously used to explain the visual perception of texture-defined form, can also account for the tactile perception of texture-defined form. This result is interesting because, first, relatively little is known about the neural mechanisms of tactile form perception, and second, the generalization of the model may reflect a canonical computation at work in both visual and somatosensory cortex. We 3D-printed test objects comprising a regular, rectangular array of raised, oriented bars measuring 0.75 × 0.75 × 3 mm (width × height × length) that were centre-to-centre spaced by 4 mm. Bars on the left-hand-side of a test object were horizontal, and those on the right were vertical, thus defining a texture boundary. We independently jittered the orientations of bars by drawing random numbers from a uniform distribution; across trials, we systematically increased jitter from 0° (i.e., no jitter) to ±90° (i.e., no boundary). Blindfolded participants (n = 25) used the preferred index finger pad to actively scan objects for 10 seconds before reporting the texture boundary's orientation (vertical or horizontal; randomised across trials). Results showed a threshold jitter of ±52.7° (i.e., the jitter at which the boundary orientation was only just discriminable). Computational modelling indicated that the first stage of the FRF model is a Gabor function tuned to spatial frequency = 0.23 cycles per mm with extent = 2.53 mm (full-width at half-maximum). We discuss this result with regard to neuronal receptive field structure in non-human primate somatosensory cortex.

Nutrition in Conservative Kidney Management: From Evidence to Practice.

Conservative kidney management (CKM) is a treatment option for kidney failure, particularly for the elderly and those with co-morbidities. Dietitians can play an important role in the provision of CKM by enhancing patients' quality of life through the management of nutrition impact symptoms (symptoms that result in decreased eating, including anorexia, nausea, dry mouth, and taste changes), as well as symptoms that result from malnutrition, including fatigue, weakness, activity intolerance, slow wound healing, and low mood. There are many gaps in the literature regarding optimal nutritional recommendations for patients on CKM. More research is needed on symptom management and interventions to delay or slow the progression of malnutrition and frailty. This article provides an overview of important nutritional considerations, a synthesis of the current literature, and recommendations for application of evidence into the practice of CKM.

Evaluation of a Structured Nutrition Competence Program for Dietitian Assistants.

OBJECTIVE: To explore the perspectives of dietitian assistants in a tertiary teaching hospital in Sydney, Australia, following the implementation of a formal competence and professional development program. METHODS: All currently employed dietitian assistants at a tertiary teaching hospital in Sydney were eligible to participate. Semi-structured interviews were undertaken by two student dietitians. Transcripts were returned to participants for interviewee transcript review and further clarification of information. Transcripts were qualitatively described. RESULTS: A total of 9 dietitian assistants participated in interviews in October 2019. The average age of participants was 45.11 yrs (range 29-59) and 90% were female (n=8). The average length of employment was 197 months (range 3-516). Three themes emerged including: (a) new job satisfaction, (b) positive influence of the dietitian assistant educator, and (c) challenges of new processes and responsibilities. CONCLUSION: A supported structured competence and professional development program has provided dietitian assistants with new skills and renewed job satisfaction. Further research should consider the impact of the newly developed skills of dietitian assistants on patient care and outcome measures.

Nutritional Care of Patients Admitted to Hospital for Alcohol Withdrawal: A 5-Year Retrospective Audit.

AIM: The aim of this study was to describe the characteristics and the nutritional approaches implemented with patients undergoing alcohol withdrawal. METHODS: A retrospective analysis of medical records for patients admitted to a tertiary hospital for alcohol withdrawal was completed over a 5-year period 2013-2017. Data on nutrition-related assessment and management were extracted and descriptively analysed. RESULTS: A total of 109 medical records were included (M = 73, F = 36), with the mean age of patients 47.3 years (SD ± 11.2, range 22-70). The average length of stay was 3.7 days (SD ± 3.9, range 0.70-27.8). Approaches towards nutritional care emerged from micronutrient assessment and supplementation and/or dietetic consultation. Nutrition-related biochemistry data was available for most patients, notably serum levels of sodium, urea and creatinine (102 patients; 93.5%) and magnesium and phosphate (66 patients, 60.5%). There was evidence of some electrolyte abnormalities on admission to hospital. Eight patients had serum micronutrient status assessed; no patients had serum thiamine levels assessed. Parenteral thiamine was provided to 96 patients (88.0%) for 1.9 days (SD ± 1.1, range 1.0-6.0) with a mean dose of 2458.7 mg (SD ± 1347.6, range 300-6700 mg). Multivitamin supplementation was provided to 24 patients (22.0%). Only 23 patients (21.2%) were seen by a dietician of whom 16 underwent a comprehensive nutritional assessment and 3 were screened using the malnutrition screening tool. CONCLUSION: Inconsistent nutritional assessment and management practices were identified across a diverse population group, whilst nutritional professionals were underutilized. Future research should benchmark current guidelines and multidisciplinary approaches considering the role of nutritional specialists in the team.

Systematic review of nutritional interventions for people admitted to hospital for alcohol withdrawal.

AIM: The aim of this review is to describe the nature of nutritional interventions for people admitted to hospital for alcohol withdrawal reported in the scientific literature and the health outcomes achieved. METHODS: The review protocol was registered with PROSPERO (CRD42017081884). The following databases were systematically searched following the PRISMA protocol: CINAHL, MEDLINE, PsycARTICLES, PsycINFO, Scopus and Web of Science. Eligible studies were those published in English, in a hospital inpatient setting with the primary reason for admission being alcohol withdrawal. Studies of patient populations with the diagnosis of pancreatitis or liver cirrhosis were excluded. Studies were screened for eligibility, and data were extracted and descriptively analysed. Identified articles were assessed using the Quality Criteria Checklist for Primary Research produced by the Academy of Nutrition and Dietetics. RESULTS: Fourteen studies met the inclusion criteria. Given the heterogeneity of studies, only a descriptive analysis of interventions could be achieved. Nutrition interventions included supplementation with thiamine, multivitamins, amino acids, antioxidant compounds, probiotics, magnesium or were educational interventions. Outcome measures included memory function, biochemical and anthropometrical indices, withdrawal symptoms, bowel flora levels and nutrition knowledge. However, the overall body of evidence was limited, particularly as there was a wide variation in participant age, study designs and duration of interventions. CONCLUSIONS: A wide range of nutrition interventions were identified, mostly involving nutrient supplements ameliorating inadequacies. Future research might also consider total dietary interventions as well as studies on the perspectives of people undergoing alcohol withdrawal.

Lean Body Mass Associated with Upper Body Strength in Healthy Older Adults While Higher Body Fat Limits Lower Extremity Performance and Endurance.

Impaired strength adversely influences an older person's ability to perform activities of daily living. A cross-sectional study of 117 independently living men and women (age = 73.4 ± 9.4 year; body mass index (BMI) = 27.6 ± 4.8 kg/m²) aimed to assess the association between body composition and: (1) upper body strength (handgrip strength, HGS); (2) lower extremity performance (timed up and go (TUG) and sit to stand test (STS)); and (3) endurance (6-minute walk (SMWT). Body composition (% fat; lean body mass (LBM)) was assessed using bioelectrical impedance. Habitual physical activity was measured using the Minnesota Leisure Time Physical Activity Questionnaire (MLTPA) and dietary macronutrient intake, assessed using 24 h recalls and 3-day food records. Regression analyses included the covariates, protein intake (g/kg), MLTPA, age and sex. For natural logarithm (Ln) of right HGS, LBM (p < 0.001) and % body fat (p < 0.005) were significant (r² = 46.5%; p < 0.000). For left LnHGS, LBM (p < 0.000), age (p = 0.036), protein intake (p = 0.015) and LnMLTPA (p = 0.015) were significant (r² = 0.535; p < 0.000). For SMW, % body fat, age and LnMLTPA were significant (r² = 0.346; p < 0.000). For STS, % body fat and age were significant (r² = 0.251; p < 0.000). LBM is a strong predictor of upper body strength while higher % body fat and lower physical activity are associated with poorer outcomes on tests of lower extremity performance.

Childhood bone mineral content is associated with methylation status of the RXRA promoter at birth.

Maternal vitamin D deficiency has been associated with reduced offspring bone mineral accrual. Retinoid-X receptor-alpha (RXRA) is an essential cofactor in the action of 1,25-dihydroxyvitamin D (1,25[OH]2 -vitamin D), and RXRA methylation in umbilical cord DNA has been associated with later offspring adiposity. We tested the hypothesis that RXRA methylation in umbilical cord DNA collected at birth is associated with offspring skeletal development, assessed by dual-energy X-ray absorptiometry, in a population-based mother-offspring cohort (Southampton Women's Survey). Relationships between maternal plasma 25-hydroxyvitamin D (25[OH]-vitamin D) concentrations and cord RXRA methylation were also investigated. In 230 children aged 4 years, a higher percent methylation at four of six RXRA CpG sites measured was correlated with lower offspring bone mineral content (BMC) corrected for body size (ß = -2.1 to -3.4 g/SD, p = 0.002 to 0.047). In a second independent cohort (n = 64), similar negative associations at two of these CpG sites, but positive associations at the two remaining sites, were observed; however, none of the relationships in this replication cohort achieved statistical significance. The maternal free 25(OH)-vitamin D index was negatively associated with methylation at one of these RXRA CpG sites (ß = -3.3 SD/unit, p = 0.03). Thus, perinatal epigenetic marking at the RXRA promoter region in umbilical cord was inversely associated with offspring size-corrected BMC in childhood. The potential mechanistic and functional significance of this finding remains a subject for further investigation.

Epigenetic regulation of ABCG2 gene is associated with susceptibility to xenobiotic exposure.

A highly conserved defence mechanism has evolved to protect cells from oxidative stress and xenobiotic exposure. A network of coupled xenobiotic metabolizing enzymatic reactions (XMEs) converts free oxidative radicals to less damaging metabolites, while efflux pumps remove toxins and XME derivatives from the cell. These mechanisms have been well studied in the contexts of hypoxia and Multidrug Resistance (MDR). Exposure of ruminants to fungal toxins leads to hepatotoxicosis and subsequent skin eczema (FE) depending upon toxic burden. Using toxin challenge in sheep we have investigated the potential for epigenetic regulation in cellular responses to xenobiotic exposure with a focus on the efflux protein ABCG2 which functions in Phase III of the defence mechanism. We show that 'resistance' to FE disease is positively associated with ABCG2 expression, and inversely correlated with DNA methylation state at CpG sites in the regulatory region of the ABCG2 gene. The analytical sensitivity provided by the Sequenom EpiTyper MS platform allows resolution of individual CpG sites varying significantly with disease progression, informing fine mapping of relevant transcription factor bindings which underpin this epigenetic response. Our findings indicate that epigenetic mechanisms are important to xenobiotic responses, suggest useful diagnostic markers and raise potential opportunities for disease remediation. This article is part of a Special Section entitled: Understanding genome regulation and genetic diversity by mass spectrometry.

Phenotypic diversity and epigenomic variation - The utility of mass spectrometric analysis of DNA methylation.

Epigenomic variation may underlie phenotypic diversity that is not attributable to differences in genomic sequence. Such processes provide an organism the flexibility to respond to changing environmental cues within its lifetime, and perhaps its offspring's lifetime, and would therefore be expected to confer a selective advantage in evolutionary terms. Analysis of epigenomic variation within a population may be both a useful measure of developmental exposures and an indicator of future phenotype. A key molecular indicator of epigenomic variation in organisms is the chemical modification of DNA by methylation at specific nucleotide residues in the genome. Here we discuss how mass spectrometry can be utilised to provide quantitative analysis of DNA methylation patterns across populations. This article is part of a Special Section entitled: Understanding genome regulation and genetic diversity by mass spectrometry.

Evaluation of methylation status of the eNOS promoter at birth in relation to childhood bone mineral content.

Our previous work has shown associations between childhood adiposity and perinatal methylation status of several genes in umbilical cord tissue, including endothelial nitric oxide synthase (eNOS). There is increasing evidence that eNOS is important in bone metabolism; we therefore related the methylation status of the eNOS gene promoter in stored umbilical cord to childhood bone size and density in a group of 9-year-old children. We used Sequenom MassARRAY to assess the methylation status of two CpGs in the eNOS promoter, identified from our previous study, in stored umbilical cords of 66 children who formed part of a Southampton birth cohort and who had measurements of bone size and density at age 9 years (Lunar DPXL DXA instrument). Percentage methylation varied greatly between subjects. For one of the two CpGs, eNOS chr7:150315553 + , after taking account of age and sex, there were strong positive associations between methylation status and the child's whole-body bone area (r = 0.28, P = 0.02), bone mineral content (r = 0.34, P = 0.005), and areal bone mineral density (r = 0.34, P = 0.005) at age 9 years. These associations were independent of previously documented maternal determinants of offspring bone mass. Our findings suggest an association between methylation status at birth of a specific CpG within the eNOS promoter and bone mineral content in childhood. This supports a role for eNOS in bone growth and metabolism and implies that its contribution may at least in part occur during early skeletal development.

Epigenetic gene promoter methylation at birth is associated with child's later adiposity.

OBJECTIVE: Fixed genomic variation explains only a small proportion of the risk of adiposity. In animal models, maternal diet alters offspring body composition, accompanied by epigenetic changes in metabolic control genes. Little is known about whether such processes operate in humans. RESEARCH DESIGN AND METHODS: Using Sequenom MassARRAY we measured the methylation status of 68 CpGs 5' from five candidate genes in umbilical cord tissue DNA from healthy neonates. Methylation varied greatly at particular CpGs: for 31 CpGs with median methylation ≥5% and a 5-95% range ≥10%, we related methylation status to maternal pregnancy diet and to child's adiposity at age 9 years. Replication was sought in a second independent cohort. RESULTS: In cohort 1, retinoid X receptor-α (RXRA) chr9:136355885+ and endothelial nitric oxide synthase (eNOS) chr7:150315553+ methylation had independent associations with sex-adjusted childhood fat mass (exponentiated regression coefficient [ß] 17% per SD change in methylation [95% CI 4-31], P = 0.009, n = 64, and ß = 20% [9-32], P < 0.001, n = 66, respectively) and %fat mass (ß = 10% [1-19], P = 0.023, n = 64 and ß =12% [4-20], P = 0.002, n = 66, respectively). Regression analyses including sex and neonatal epigenetic marks explained >25% of the variance in childhood adiposity. Higher methylation of RXRA chr9:136355885+, but not of eNOS chr7:150315553+, was associated with lower maternal carbohydrate intake in early pregnancy, previously linked with higher neonatal adiposity in this population. In cohort 2, cord eNOS chr7:150315553+ methylation showed no association with adiposity, but RXRA chr9:136355885+ methylation showed similar associations with fat mass and %fat mass (ß = 6% [2-10] and ß = 4% [1-7], respectively, both P = 0.002, n = 239). CONCLUSIONS: Our findings suggest a substantial component of metabolic disease risk has a prenatal developmental basis. Perinatal epigenetic analysis may have utility in identifying individual vulnerability to later obesity and metabolic disease.

Normal development following chromatin transfer correlates with donor cell initial epigenetic state.

If the full potential of chromatin transfer (CT) technology is to be realized for both animal production and biomedical applications it is imperative that the efficiency of the reprogramming process be improved, and the potential for deleterious development be eliminated. Generation of the first cloned animals from adult somatic cells demonstrated that development is substantially an epigenetic process (Wilmut I, Schnieke AE, McWhir J, Kind AJ, Campbell KH, 1997. Viable offspring derived from fetal and adult mammalian cells. Nature. 385(6619): 810-813.). In this study, we provide preliminary evidence that the epigenetic state of the donor cell, may be valuable in assessing potential cloning success. We have measured key indicators of cellular epigenetic state in both serially derived cell populations of the same genetic origin, but differing in epigenomic status, and in a distinct cohort of donor cell populations with diverse genetic origins and epigenomic status. Specifically, the relative abundance of particular histone modifications in donor populations prior to manipulation has been correlated with the measurable variance in reprogramming efficiencies observed following CT, as defined by the number of resulting live births and healthy progeny, and the concomitant incidence of deleterious growth measures (notably the appearance of large offspring syndrome (LOS)). Thus, we suggest that the likely outcome and relative success of cloning may be predictable based on the expression of discriminating histone marks present in the donor cell population before CT. This approach may provide the basis of a prognostic signature for the future evaluation and risk assessment of putative donor cells prior to CT, and thus increase future cloning success and alleviate the incidence of abnormal development.

LIF/STAT3 controls ES cell self-renewal and pluripotency by a Myc-dependent mechanism.

Murine ES cells can be maintained as a pluripotent, self-renewing population by LIF/STAT3-dependent signaling. The downstream effectors of this pathway have not been previously defined. In this report, we identify a key target of the LIF self-renewal pathway by showing that STAT3 directly regulates the expression of the Myc transcription factor. Murine ES cells express elevated levels of Myc and following LIF withdrawal, Myc mRNA levels collapse and Myc protein becomes phosphorylated on threonine 58 (T58), triggering its GSK3beta dependent degradation. Maintained expression of stable Myc (T58A) renders self-renewal and maintenance of pluripotency independent of LIF. By contrast, expression of a dominant negative form of Myc antagonizes self-renewal and promotes differentiation. Transcriptional control by STAT3 and suppression of T58 phosphorylation are crucial for regulation of Myc activity in ES cells and therefore in promoting self-renewal. Together, our results establish a mechanism for how LIF and STAT3 regulate ES cell self-renewal and pluripotency.

Recruitment of Thr 319-phosphorylated Ndd1p to the FHA domain of Fkh2p requires Clb kinase activity: a mechanism for CLB cluster gene activation.

Activation of the CLB gene cluster through the assembly of Mcm1p-Fkh2p complexes at target promoters is essential for mitotic entry and transition through M phase. We show that the activation of this mitotic transcriptional program is dependent on the recruitment of Ndd1p, a coactivator that performs its essential function by acting through Fkh2p. Although an essential gene, NDD1 is dispensable in cells expressing a truncated form of Fkh2p lacking its C terminus. When phosphorylated on T319, Ndd1p is recruited to CLB cluster promoters by association with the forkhead-associated (FHA) domain of Fkh2p. Substitution of T319 for alanine significantly reduces recruitment of Ndd1p, resulting in loss of normal transcriptional regulation, severe impairment of cell growth, and a budding defect reminiscent of cells with a Cdk-Clb kinase deficiency. Finally, we show that phosphorylation of T319 and recruitment of Ndd1p to CLB2 and SWI5 promoters is dependent on Cdc28-Clb kinase activity. These data provide a model describing the activation of G2/M transcription through the phosphorylation of Ndd1p by Cdc28-Clb kinase activity.