Body composition assessment in 6-month-old infants: A comparison of two- and three-compartment models using data from the Baby-bod study.

BACKGROUND/OBJECTIVES: An appreciation of infant body composition is helpful to understand the 'quality' of growth in early life. Air displacement plethysmography (ADP) using PEA POD and the deuterium dilution (DD) technique are commonly used body composition approaches in infants. We evaluated the comparability of body composition assessed using both techniques with two-compartment (2C) and three-compartment (3C) models in 6-month-old infants. SUBJECTS/METHODS: Infant fat mass (FM) and percent fat mass (%FM) obtained from a 2C model using PEA POD (2C-PP) and a 2C model using the deuterium dilution technique (2C-DD) were compared to those derived from a 3C model, and to each other, using Bland-Altman analysis and Deming regression. RESULTS: Measurements were available from 68 infants (93% Caucasian, 53% male). The mean biases were not significant between any of the method comparisons. However, significant constant and proportional biases were identified in 2C-DD vs 3C and 2C-PP vs 2C-DD, but not in the 2C-PP vs 3C comparison. Furthermore, we observed significant associations between the mean differences and infants' percent total body water (%TBW). CONCLUSIONS: While no significant between-method mean differences were found in body composition estimates, some comparisons revealed significant constant and proportional biases and notable associations between the mean differences and %TBW were observed. Our results emphasise the importance of method choice, ensuring methodological uniformity in long-term studies, and carefully considering and regulating multiple pre-analytical variables, such as the hydration status of the participants.

Trends and associations between maternal characteristics and infant birthweight among Indigenous and non-Indigenous people in Tasmania, Australia: a population-based study.

OBJECTIVE: This study aimed to investigate the trends and associations of maternal characteristics and birthweight among Indigenous and non-Indigenous infants. STUDY DESIGN: This was a retrospective population-based study. METHODS: Fourteen years (2005-2018) of birthweight and perinatal health data of live-born singletons and their mothers obtained from the Tasmanian Data Linkage Unit were used to assess the trends and associations between maternal characteristics and infant birthweight using regression modelling. RESULTS: Compared with non-Indigenous mothers (n = 76,750), Indigenous mothers (n = 3805) had a significantly higher prevalence of risk factors during the 14-year period. Although the prevalence of prepregnancy obesity and gestational diabetes mellitus (GDM) markedly increased in both groups, the rate of increase was higher (P < 0.001) for Indigenous than non-Indigenous mothers. Smoking, alcohol consumption and illegal drug use during pregnancy reduced over the years, and there was no significant difference in the rate of reduction between the groups. Large-for-gestational-age (LGA) births increased while small-for-gestational-age (SGA) births decreased in both groups over time. In addition, high birthweight (HBW) births decreased while low birthweight (LBW) births increased. The rates of increase in LGA and LBW births and the rates of decrease in SGA and HBW births were significantly higher in Indigenous mothers compared with non-Indigenous mothers (P < 0.001 for all). The association between Indigenous ethnicity and LBW and SGA births weakened after adjusting for other confounding maternal and perinatal variables. LBW and SGA were positively associated with Indigenous ethnicity, age <18 years, smoking, alcohol consumption and illegal drug use, pre-eclampsia, underweight prepregnancy body mass index and low socio-economic status. Women with higher parity, pre-existing diabetes and prepregnancy overweight or obesity were more likely to give birth to an infant with HBW or LGA. CONCLUSIONS: The prevalence of risk factors for abnormal birthweight is higher among Tasmanian Indigenous mothers, contributing to a gap in birthweight outcomes between Indigenous and non-Indigenous infants. The dramatic increase in prepregnancy obesity and GDM in both groups highlight the importance of screening and management of GDM during pregnancy. Comprehensive programmes co-designed and co-managed in consultation with Indigenous people are needed to support healthy lifestyle choices among Indigenous women to address the barriers to individuals adopting behaviour change and to help close the health outcomes-related gap between Indigenous and non-Indigenous mothers and infants.

Synbiotics as Supplemental Therapy for the Alleviation of Chemotherapy-Associated Symptoms in Patients with Solid Tumours.

Chemotherapy is still the first line of treatment for most cancer patients. Patients receiving chemotherapy are generally prone to infections, which result in complications, such as sepsis, mucositis, colitis, and diarrhoea. Several nutritional approaches have been trialled to counter the chemotherapy-associated side effects in cancer patients, but none have yet been approved for routine clinical use. One of the approaches to reduce or avoid chemotherapy-associated complications is to restore the gut microbiota. Gut microbiota is essential for the healthy functioning of the immune system, metabolism, and the regulation of other molecular responses in the body. Chemotherapy erodes the mucosal layer of the gastrointestinal tract and results in the loss of gut microbiota. One of the ways to restore the gut microbiota is through the use of probiotics. Probiotics are the 'good' bacteria that may provide health benefits if consumed in appropriate amounts. Some studies have highlighted that the consumption of probiotics in combination with prebiotics, known as synbiotics, may provide better health benefits when compared to probiotics alone. This review discusses the different nutritional approaches that have been studied in an attempt to combat chemotherapy-associated side effects in cancer patients with a particular focus on the use of pre-, pro- and synbiotics.

Capsaicin and Zinc Signalling Pathways as Promising Targets for Managing Insulin Resistance and Type 2 Diabetes.

The global burden of type 2 diabetes (T2DM) has led to significant interest in finding novel and effective therapeutic targets for this chronic disorder. Bioactive food components have effectively improved abnormal glucose metabolism associated with this disease. Capsaicin and zinc are food components that have shown the potential to improve glucose metabolism by activating signalling events in the target cells. Capsaicin and zinc stimulate glucose uptake through the activation of distinct pathways (AMPK and AKT, respectively); however, calcium signal transduction seems to be the common pathway between the two. The investigation of molecular pathways that are activated by capsaicin and zinc has the potential to lead to the discovery of new therapeutic targets for T2DM. Therefore, this literature review aims to provide a summary of the main signalling pathways triggered by capsaicin and zinc in glucose metabolism.

Gestational weight gain and postpartum weight retention in Tasmanian women: The Baby-bod Study.

Many factors can negatively impact perinatal outcomes, including inappropriate gestational weight gain (GWG). Despite having the greatest potential to influence maternal and infant health, there is a lack of consensus regarding the GWG consistent with a healthy pregnancy. To date, GWG in Northern Tasmania remains understudied. We investigated how maternal pre-pregnancy body mass index (BMI) is related to weight gain during pregnancy and weight retention post-partum, and how maternal pre-pregnancy BMI is related to the mode of delivery. Approximately 300 Tasmanian mothers (n = 291 for mode of delivery and n = 282 for GWG) were included in this study. Analysis of variance and chi square tests were conducted to assess differences in BW of mothers across BMI categories and differences between categorical variables; respectively. Based on pre-pregnancy BMI, mothers were assigned to one of three groups, with healthy weight (<25 kg m-2), with overweight (25-29.9 kg m-2), or with obesity (>30 kg m-2). Pre-pregnancy BMI and body weight (BW) were significantly associated (p<0.001) with post-partum BW at 3 and 6 months. Only 25% of mothers with a normal weight BMI, 34% with overweight and 13% with obesity, achieved the Institute of Medicine (IOM) recommendation for GWG. Interestingly, a number of women in our cohort lost weight during gestation (1.5, 9 and 37% in <25, 25-29.9 and >30 kg m-2 groups, respectively). Further, women with obesity showed the lowest level of BW fluctuation and retained less weight post-partum. The highest number of caesarean sections were observed in mothers who exceeded GWG recommendations. Most mothers either exceeded or failed to achieve IOM recommendations for GWG. To improve the generalisability of these findings, this study should be replicated in a larger representative sample of the Tasmanian maternal population.

Capsaicin and Zinc Promote Glucose Uptake in C2C12 Skeletal Muscle Cells through a Common Calcium Signalling Pathway.

Capsaicin and zinc have recently been highlighted as potential treatments for glucose metabolism disorders; however, the effect of these two natural compounds on signalling pathways involved in glucose metabolism is still uncertain. In this study, we assessed the capsaicin- or zinc- induced activation of signalling molecules including calcium/calmodulin-dependent protein kinase 2 (CAMKK2), cAMP-response element-binding protein (CREB), and target of rapamycin kinase complex 1 (TORC1). Moreover, the expression status of genes associated with the control of glucose metabolism was measured in treated cells. The activation of cell signalling proteins was then evaluated in capsaicin- or zinc treated cells in the presence or absence of cell-permeant calcium chelator (BAPTA-AM) and the CAMKK inhibitor (STO-609). Finally, capsaicin- and zinc-induced glucose uptake was measured in the cells pre-treated with or without BAPTA-AM. Our results indicate that calcium flux induced by capsaicin or zinc led to activation of calcium signalling molecules and promoting glucose uptake in skeletal muscle cells. Pharmacological inhibition of CAMKK diminished activation of signalling molecules. Moreover, we observed an increase in intracellular cAMP levels in the cells after treatment with capsaicin and zinc. Our data show that capsaicin and zinc mediate glucose uptake in C2C12 skeletal muscle cells through the activation of calcium signalling.

WHO Child Growth Standards in context: The Baby-bod Project - Observational study in Tasmania.

Objective: This research evaluated (1) differences in body size and composition of Tasmanian infants at birth and 3 and 6 months postpartum compared with WHO child growth standards and (2) body composition changes in Tasmanian infants at the extremes of the weight-for-length (WFL) spectrum. Design: Observational study. Setting: A hospital in Northern Tasmania, Australia. Patients: 315 healthy infants (~90% Caucasian) born between 2017 and 2019 in Tasmania. Interventions: Body composition and anthropometric measures at 0, 3 and 6 months. Main outcome measures: Growth characteristics at birth and growth trajectories from 0 to 6 months were compared against WHO child growth standards for 0-2 years. Results: Overall, growth of Tasmanian infants in the first 6 months of life was similar to the global prescriptive standards. Trajectories of fat mass (FM) and fat-free mass (FFM) accrual in infants from the extremes of the size spectrum appear to converge at the 6-month time point. Infants in the lower extremity demonstrated the most precipitous accrual in percentage FM (and the steepest decline in percentage FFM), compared with all other infants. Conclusion: No significant deviations of growth were observed in Tasmanian infants from 0 to 6 months in comparison to the WHO prescriptive growth standards. Infants below the third percentile WFL showed the most precipitous increase in FM accretion. Periodic comparisons local infants with global standards will enable identification of significant deviations from optimal growth patterns.

TRPV1 Activation by Capsaicin Mediates Glucose Oxidation and ATP Production Independent of Insulin Signalling in Mouse Skeletal Muscle Cells.

BACKGROUND: Insulin resistance (IR), a key characteristic of type 2 diabetes (T2DM), is manifested by decreased insulin-stimulated glucose transport in target tissues. Emerging research has highlighted transient receptor potential cation channel subfamily V member (TRPV1) activation by capsaicin as a potential therapeutic target for these conditions. However, there are limited data on the effects of capsaicin on cell signalling molecules involved in glucose uptake. METHODS: C2C12 cells were cultured and differentiated to acquire the myotube phenotype. The activation status of signalling molecules involved in glucose metabolism, including 5' adenosine monophosphate-activated protein kinase (AMPK), calcium/calmodulin-dependent protein kinase 2 (CAMKK2), extracellular signal-regulated protein kinases 1 and 2 (ERK1/2), protein kinase B (AKT), and src homology phosphatase 2 (SHP2), was examined. Finally, activation of CAMKK2 and AMPK, and glucose oxidation and ATP levels were measured in capsaicin-treated cells in the presence or absence of TRPV1 antagonist (SB-452533). RESULTS: Capsaicin activated cell signalling molecules including CAMKK2 and AMPK leading to increased glucose oxidation and ATP generation independent of insulin in the differentiated C2C12 cells. Pharmacological inhibition of TRPV1 diminished the activation of CAMKK2 and AMPK as well as glucose oxidation and ATP production. Moreover, we observed an inhibitory effect of capsaicin in the phosphorylation of ERK1/2 in the mouse myotubes. CONCLUSION: Our data show that capsaicin-mediated stimulation of TRPV1 in differentiated C2C12 cells leads to activation of CAMKK2 and AMPK, and increased glucose oxidation which is concomitant with an elevation in intracellular ATP level. Further studies of the effect of TRPV1 channel activation by capsaicin on glucose metabolism could provide novel therapeutic utility for the management of IR and T2DM.

Exclusivity of breastfeeding and body composition: learnings from the Baby-bod study.

BACKGROUND: This report evaluated the breastfeeding status in a Tasmanian cohort and its effects on infant and maternal anthropometry and body composition. METHODS: An observational-cohort analysis of self-reported feeding data from 175 Tasmanian mother-baby dyads (recruited via in-person contact between September 2017 and October 2019), was executed. Only mothers who were ≥ 18 years of age, who had a singleton pregnancy and were able to speak and understand English, were included in the study. Infants outside a gestational age range between 37+ 0 and 41+ 6 weeks were excluded. Infant (using Air Displacement Plethysmography) and maternal body composition was assessed at 0, 3 and 6 months. Analysis of variance with relevant statistical corrections were utilised for cross-sectional and longitudinal comparisons between non-exclusively breastfed (neBF) and exclusively breastfed (eBF) groups. RESULTS: Fat-free mass was significantly higher [t = 2.27, df = 98, P = 0.03, confidence interval (CI) 0.03, 0.48] in neBF infants at 6 months (5.59 ± 0.59 vs 5.33 ± 0.50 kg) despite a higher mean fat-free mass in eBF infants at birth (2.89 ± 0.34 vs 3.01 ± 0.35 kg). Weak evidence for different fat mass index trajectories was observed for eBF and neBF infants in the first 6 months of life (ANOVA, F = 2.42, df = 1.9, P = 0.09) with an inversion in fat mass index levels between 3 and 6 months. Body Mass Index (BMI) trajectories were significantly different in eBF and neBF mothers through pregnancy and the first 6 months postpartum (ANOVA, F = 5.56, df = 30.14, P = 0.01). Compared with eBF mothers, neBF mothers retained significantly less weight (t = - 2.754, df = 158, P = 0.02, CI -6.64, - 1.09) at 3 months (0.68 ± 11.69 vs 4.55 ± 6.08 kg) postpartum. Prevalence for neBF was incrementally higher in mothers with a normal BMI compared to mothers with obesity, and mothers who underwent surgical or medical intervention during birth were less likely to exclusively breastfeed. CONCLUSIONS: Infants with different feeding patterns may display varying growth patterns in early life and sustained breastfeeding can contribute to greater postpartum maternal weight loss.

Determinants of Infant Adiposity across the First 6 Months of Life: Evidence from the Baby-bod study.

Excess adiposity in infancy may predispose individuals to obesity later in life. The literature on determinants of adiposity in infants is equivocal. In this longitudinal cohort study, we investigated pre-pregnancy, prenatal and postnatal determinants of different adiposity indices in infants, i.e., fat mass (FM), percent FM (%FM), fat mass index (FMI) and log-log index (FM/FFMp), from birth to 6 months, using linear mixed-effects regression. Body composition was measured in 322, 174 and 109 infants at birth and 3 and 6 months afterwards, respectively, utilising air displacement plethysmography. Positive associations were observed between gestation length and infant FM, maternal self-reported pre-pregnancy body mass index and infant %FM, and parity and infant %FM and FMI at birth. Surprisingly, maternal intake of iron supplements during pregnancy was associated with infant FM, %FM and FMI at 3 months and FM/FFMp at 6 months. Male infant sex and formula feeding were negatively associated with all adiposity indices at 6 months. In conclusion, pre-pregnancy and pregnancy factors influence adiposity during early life, and any unfavourable impacts may be modulated postnatally via infant feeding practices. Moreover, as these associations are dependent on the adiposity indices used, it is crucial that researchers use conceptually and statistically robust approaches such as FM/FFMp.

Gestational Diabetes Mellitus and Infant Adiposity at Birth: A Systematic Review and Meta-Analysis of Therapeutic Interventions.

Exposure to untreated gestational diabetes mellitus (GDM) in utero increases the risk of obesity and type 2 diabetes in adulthood, and increased adiposity in GDM-exposed infants is suggested as a plausible mediator of this increased risk of later-life metabolic disorders. Evidence is equivocal regarding the impact of good glycaemic control in GDM mothers on infant adiposity at birth. We systematically reviewed studies reporting fat mass (FM), percent fat mass (%FM) and skinfold thicknesses (SFT) at birth in infants of mothers with GDM controlled with therapeutic interventions (IGDMtr). While treating GDM lowered FM in newborns compared to no treatment, there was no difference in FM and SFT according to the type of treatment (insulin, metformin, glyburide). IGDMtr had higher overall adiposity (mean difference, 95% confidence interval) measured with FM (68.46 g, 29.91 to 107.01) and %FM (1.98%, 0.54 to 3.42) but similar subcutaneous adiposity measured with SFT, compared to infants exposed to normal glucose tolerance (INGT). This suggests that IGDMtr may be characterised by excess fat accrual in internal adipose tissue. Given that intra-abdominal adiposity is a major risk factor for metabolic disorders, future studies should distinguish adipose tissue distribution of IGDMtr and INGT.

Anthropometry-based prediction of body fat in infants from birth to 6 months: the Baby-bod study.

BACKGROUND/OBJECTIVES: Prediction equations generated from anthropometric measures are frequently used to quantify paediatric body composition. We tested the agreeability and predictive power of select (Lingwood and Aris) fat mass prediction equations against body fat measured via ADP; and generated and evaluated new anthropometry-based models for use in the first 6 months of life. SUBJECTS/METHODS: Data were obtained from 278 white European Australian infants at birth, 3 and 6 months. Prediction models (i.e. Baby-bod models) were generated for each time point via stepwise linear regression and compared for agreeability with ADP via limits of agreement, mean difference and total bias in Bland-Altman analyses. Predictive power of all equations in comparison to ADP were assessed using linear regression analysis. RESULTS: Overall, there was poor agreeability between percent body fat predicted via published equations and ADP. Proportional bias was detected for both methods (i.e. published equations and Baby-bod models) of body fat prediction. At birth, both Lingwood and BB0 equations overestimated percent body fat at the lower end of the FM spectrum. This trend was repeated at 3 months with all equations displaying a propensity to overestimate body fat at lower FM levels and underestimate at higher FM levels. CONCLUSIONS: The results indicate that anthropometry, although less costly and relatively easier to implement, does not always produce comparable results with objective measures such as ADP. Given the importance of the accurate assessment of physical growth, including body composition in early life, it is timely to recommend the increased utilisation of techniques such as ADP.

Anti-Heartburn Effects of Sugar Cane Flour: A Double-Blind, Randomized, Placebo-Controlled Study.

Gastroesophageal reflux disease (GERD) affects approximately 20% of Australians. Patients suffer a burning sensation known as heartburn due to the movement of acidic stomach content into the esophagus. There is anecdotal evidence of the effectiveness of prebiotic sugarcane flour in controlling symptoms of GERD. This pilot study aimed to investigate the effectiveness of a prebiotic sugarcane flour in alleviating symptoms in medically-diagnosed GERD patients. This pilot study was a single center, double-blinded, placebo-controlled randomized trial conducted on 43 eligible participants. The intervention group (n = 22) were randomized to receive 3 g of sugarcane flour per day, and the control group (n = 21) received 3 g of cellulose placebo per day. Symptoms of gastroesophageal reflux disease were assessed before and after three weeks treatment using the validated Gastroesophageal Reflux Disease-Health Related Quality of Life questionnaire (GERD-HRQL). After three weeks there were significant differences in symptoms for heartburn, regurgitation, and total symptoms scores (p < 0.05) between the sugarcane flour and placebo. Mean GERD-HRQL scores increased in the placebo group for regurgitation (mean increase 1.7; 95% CI 0.23 to 3.2; p = 0.015) and total symptom scores (2.9; 95% CI 0.26 to 5.7; p = 0.033). In contrast, there were significant reductions in heartburn (mean decrease -2.2; 95% CI -4.2 to -0.14; p = 0.037) and total symptom scores (-3.7; 95% CI -7.2 to -0.11; p = 0.044) in the intervention group. This pilot study has shown significant positive effects of sugarcane flour in the reduction of GERD symptoms, and a larger randomized controlled trial is warranted.

Diet and Multiple Sclerosis: Scoping Review of Web-Based Recommendations.

BACKGROUND: There is currently no scientific evidence supporting the use of specific diets in the management of multiple sclerosis (MS); the strongest dietary associations are observed with vitamin D and omega-3 fatty acid supplementation. Despite this, there are many websites that provide advice or suggestions about using various dietary approaches to control symptoms or disease progression. OBJECTIVE: The objective of this study was to assess the dietary advice for the symptomatic management of MS available on the internet. METHODS: This study was a systematic review of webpages that provided dietary advice for the management of MS. Webpages were selected from an internet search conducted in November 2016 using Google, Yahoo, and Bing search engines and the search term "MS diet." The first two pages of results from each search engine were included for the initial assessment. Duplicates were removed. Data extracted from websites included specific advice relating to diet and its rationale and the citation of supporting scientific literature. Authorship and credential information were reviewed to assess webpage quality. RESULTS: We included 32 webpages in the final assessment. The webpages made a wide variety of specific recommendations regarding dietary patterns and individual foods to help manage MS. The most common dietary pattern advised on these webpages was the low-fat, high-fiber balanced diet, followed by the low-saturated fat diet, near-vegetarian Swank diet, and the Paleo diet. The main categories of individual foods or nutrients suggested for addition to the diet were: supplements (especially omega-3 and vitamin D), fruits, vegetables, and lean protein. In contrast, the most commonly recommended for removal were saturated fats, dairy, gluten-containing grains, and refined sugar. These recommendations were often accompanied by rationale relating to how the particular food or nutrient may affect the development, prevalence and symptoms of MS; however, very little of this information is supported by the current scientific evidence between diet and MS. Only 9 webpages provided full authorship including credential information. CONCLUSIONS: There is a wide variety of Web-based dietary advice, which in some cases is contradictory. In most cases, this advice is the result of peoples' individual experiences and has not been scientifically tested. How people living with MS use this information is not known. These findings highlight the important role health professionals can play in assisting people living with MS in their health information-seeking behaviors.

Cyst-Like Lesions at Chondro-Osseous Junction.

This study described and histologically characterized a cyst-like lesion (CLL) at the chondro-osseous junction. Rat knees (n = 12), with or without excessive running-induced osteoarthritis (OA), were used for counting the incidence, morphological measurements, immunohistochemistry of the CLL. A typical CLL, appearing as a void space in the matrix, was located on the tidemark at the chondro-osseous junction. The content of the CLL included types II and VI collagen, proteoglycans but not intact chondrocytes. At least one CLL was found in 5/6 osteoarthritic knees and only 2/6 in the non-osteoarthritic knees. The margin of the CLL was depleted of proteoglycans. The chondrocytes around the lesion were deformed and occasionally apoptotic. Matrix metalloproteinase 13 and vascular endothelial growth factor receptor were not detected in and around the CLL. CLLs disrupt the integrity of cartilage at a mechanically critical location-the chondro-osseous junction. The significance of the CLL in cartilage biology and its potential role in OA pathogenesis warrant further investigation.

Online dietary advice for the symptomatic management of multiple sclerosis: a scoping review protocol.

OBJECTIVE AND REVIEW QUESTION: The objective of this scoping review is to identify, map and assess the range of dietary advice provided on websites for the symptomatic management of multiple sclerosis (MS), specifically in relation to the types of diets, relationship between specific food/diet/supplement and specific symptoms, citation of scientific literature to support claims and advice to consult a health professional (doctor/nutritionist/dietitian).Specifically the review question is: What dietary advice is available on websites for the symptomatic management of MS?

Zinc status of northern Tasmanian adults.

Information regarding Zn status in the Australian population is very limited. Mild deficiencies in Zn have been associated with CVD, impaired immune function and poor healing. A cross-sectional study of 497 northern Tasmanian adults (24-82 years of age) was conducted to assess Zn status. Dietary intakes were assessed by FFQ and serum concentrations of Zn were evaluated using International Zinc Nutrition Consultative Group methodology. Mean Zn intakes were 12·6 (sd 4·4) mg/d for men and 10·9 (sd 3·6) mg/d for women. It was found that 52 % of men but only 9 % of women consumed less than the Australia/New Zealand estimated average requirement for Zn. Mean serum Zn was 13·0 (sd 2·4) µmol/l in men and 13·0 (sd 2·5) µmol/l in women. Overall, 15 % of men and 7 % of women had low serum Zn levels. Furthermore, low serum Zn was observed in 18 % of men 50 years or older and 30 % of men 70 years or older. The present results suggest that mild Zn deficiency may be prevalent in older Tasmanian adults, particularly men; and due to the importance of Zn in many areas of health, this could be of public health concern.

Canine degenerative myelopathy: biochemical characterization of superoxide dismutase 1 in the first naturally occurring non-human amyotrophic lateral sclerosis model.

Mutations in canine superoxide dismutase 1 (SOD1) have recently been shown to cause canine degenerative myelopathy, a disabling neurodegenerative disorder affecting specific breeds of dogs characterized by progressive motor neuron loss and paralysis until death, or more common, euthanasia. This discovery makes canine degenerative myelopathy the first and only naturally occurring non-human model of amyotrophic lateral sclerosis (ALS), closely paralleling the clinical, pathological, and genetic presentation of its human counterpart, SOD1-mediated familial ALS. To further understand the biochemical role that canine SOD1 plays in this disease and how it may be similar to human SOD1, we characterized the only two SOD1 mutations described in affected dogs to date, E40K and T18S. We show that a detergent-insoluble species of mutant SOD1 is present in spinal cords of affected dogs that increases with disease progression. Our in vitro results indicate that both canine SOD1 mutants form enzymatically active dimers, arguing against a loss of function in affected homozygous animals. Further studies show that these mutants, like most human SOD1 mutants, have an increased propensity to form aggregates in cell culture, with 10-20% of cells possessing visible aggregates. Creation of the E40K mutation in human SOD1 recapitulates the normal enzymatic activity but not the aggregation propensity seen with the canine mutant. Our findings lend strong biochemical support to the toxic role of SOD1 in canine degenerative myelopathy and establish close parallels for the role mutant SOD1 plays in both canine and human disorders.

Make vitamin D while the sun shines, take supplements when it doesn't: a longitudinal, observational study of older adults in Tasmania, Australia.

Low vitamin D status has been associated with a number of chronic conditions, particularly in older adults. The aim of this study was to identify how best to maintain optimum vitamin D status throughout the year in this high-risk population. The main objectives of the study were to assess seasonal vitamin D status; identify the main determinants of vitamin D status; determine if taking part in the study led to alterations in participant behaviour and vitamin D status. A longitudinal design across four consecutive seasons observed ninety-one 60-85 year old community-dwelling adults in Tasmania (41π S) over 13 consecutive months, with a follow-up assessment at next winter's end. Associations between solar UVB exposure, sun protection behaviours, dietary and supplemental vitamin D with serum 25(OH)D concentrations were assessed. Variation in serum 25(OH)D demonstrated an identical pattern to solar UVB, lagging 8-10 weeks. Serum 25(OH)D was positively associated with summer UVB (mean 15.9 nmol/L; 95%CI 11.8-19.9 nmol/L, p<0.001) and vitamin D supplementation (100-600 IU/day: 95%CI 10.2 nmol/L; 0.8-19.6 nmol/L; p = 0.03; 800 IU/day: 21.0 nmol/L; 95%CI 8.1-34.0 nmol/L; p = 0.001). Seasonal variation in serum 25(OH)D was greatly diminished in supplement users. The most common alteration in participant behaviour after the study was ingesting vitamin D supplements. Post-study vitamin D supplementation ℘800 IU/day was seven times more likely than during the study resulting in mean difference in serum 25(OH)D between supplement and non-supplement users of 30.1 nmol/L (95%CI 19.4-40.8 nmol/L; p<0.001). The main limitation was homogeneity of participant ethnicity. Solar exposure in summer and ingestion of vitamin D supplements in other seasons are the most effective ways of achieving and maintaining year-round vitamin D sufficiency in older adults in the Southern hemisphere. Vitamin D supplementation has greatest effect on vitamin D status if ingested during and after winter, i.e. between the autumn and spring equinoxes.

Effect of hereditary haemochromatosis genotypes and iron overload on other trace elements.

PURPOSE: Hereditary haemochromatosis is a common genetic disorder involving dysregulation of iron absorption. There is some evidence to suggest that abnormal iron absorption and metabolism may influence the status of other important trace elements. In this study, the effect of abnormal HFE genotypes and associated iron overload on the status of other trace elements was examined. METHODS: Dietary data and blood samples were collected from 199 subjects (mean age = 55.4 years; range = 21-81 years). Dietary intakes, serum selenium, copper and zinc concentrations and related antioxidant enzymes (glutathione peroxidase and superoxide dismutase) in subjects with normal HFE genotype (n = 118) were compared to those with abnormal HFE genotype, with both normal iron status (n = 42) and iron overload (n = 39). RESULTS: For most dietary and biochemical variables measured, there were no significant differences between study groups. Red cell GPx was significantly higher in male subjects with normal genotypes and normal iron status compared to those with abnormal genotypes and normal iron status (P = 0.03) or iron overload (P = 0.001). Red cell GPx was also highest in normal women and significantly lower in the abnormal genotype and normal iron group (P = 0.016), but not in the iron overload group (P = 0.078). CONCLUSION: Although it may not be possible to exclude a small effect between the genotype groups on RBC GPx, overall, haemochromatosis genotypes or iron overload did not appear to have a significant effect on selenium, copper or zinc status.