Evaluation of the zucker diabetic fatty (ZDF) rat as a model for human disease based on urinary peptidomic profiles

Representative animal models for diabetes-associated vascular complications are extremely relevant in assessing potential therapeutic drugs. While several rodent models for type 2 diabetes (T2D) are available, their relevance in recapitulating renal and cardiovascular features of diabetes in man is not entirely clear. Here we evaluate at the molecular level the similarity between Zucker diabetic fatty (ZDF) rats, as a model of T2D-associated vascular complications, and human disease by urinary proteome analysis. Urine analysis of ZDF rats at early and late stages of disease compared to age- matched LEAN rats identified 180 peptides as potentially associated with diabetes complications. Overlaps with human chronic kidney disease (CKD) and cardiovascular disease (CVD) biomarkers were observed, corresponding to proteins marking kidney damage (eg albumin, alpha-1 antitrypsin) or related to disease development (collagen). Concordance in regulation of these peptides in rats versus humans was more pronounced in the CVD compared to the CKD panels. In addition, disease-associated predicted protease activities in ZDF rats showed higher similarities to the predicted activities in human CVD. Based on urinary peptidomic analysis, the ZDF rat model displays similarity to human CVD but might not be the most appropriate model to display human CKD on a molecular level

Cross-cultural adaptation and validation of the “spinal cord injury-falls concern scale” in the Italian population

Study design: Psychometrics study. Objective: The objective of this study was to develop an Italian version of the Spinal Cord Injury-Falls Concern Scale (SCI-FCS) and examine its reliability and validity. Setting: Multicenter study in spinal units in Northern and Southern Italy. The scale also was administered to non-hospitalized outpatient clinic patients. Methods: The original scale was translated from English to Italian using the “Translation and Cultural Adaptation of Patient-Reported Outcomes Measures” guidelines. The reliability and validity of the culturally adapted scale were assessed following the “Consensus-Based Standards for the Selection of Health Status Measurement Instruments” checklist. The SCI-FCS-I internal consistency, inter-rater, and intra-rater reliability were examined using Cronbach’s alpha coefficient and the intraclass correlation coefficient, respectively. Concurrent validity was evaluated using Pearson’s correlation coefficient with the Italian version of the short form of the Wheelchair Use Confidence Scale for Manual Wheelchair Users (WheelCon-M-I-short form). Results: The Italian version of the SCI-FCS-I was administered to 124 participants from 1 June to 30 September 2017. The mean ± SD of the SCI-FCS-I score was 16.73 ± 5.88. All SCI-FCS items were either identical or similar in meaning to the original version’s items. Cronbach’s α was 0.827 (p < 0.01), the inter-rater reliability was 0.972 (p < 0.01), and the intra-rater reliability was 0.973 (p < 0.01). Pearson’s correlation coefficient of the SCI-FCS-I scores with the WheelCon-M-I-short form was 0.56 (p < 0.01). Conclusions: The SCI-FCS-I was found to be reliable and a valid outcome measure for assessing manual wheelchair concerns about falling in the Italian population

Age-related delay in information accrual for faces: Evidence from a parametric, single-trial EEG approach

Background: In this study, we quantified age-related changes in the time-course of face processing by means of an innovative single-trial ERP approach. Unlike analyses used in previous studies, our approach does not rely on peak measurements and can provide a more sensitive measure of processing delays. Young and old adults (mean ages 22 and 70 years) performed a non-speeded discrimination task between two faces. The phase spectrum of these faces was manipulated parametrically to create pictures that ranged between pure noise (0% phase information) and the undistorted signal (100% phase information), with five intermediate steps. Results: Behavioural 75% correct thresholds were on average lower, and maximum accuracy was higher, in younger than older observers. ERPs from each subject were entered into a single-trial general linear regression model to identify variations in neural activity statistically associated with changes in image structure. The earliest age-related ERP differences occurred in the time window of the N170. Older observers had a significantly stronger N170 in response to noise, but this age difference decreased with increasing phase information. Overall, manipulating image phase information had a greater effect on ERPs from younger observers, which was quantified using a hierarchical modelling approach. Importantly, visual activity was modulated by the same stimulus parameters in younger and older subjects. The fit of the model, indexed by R2, was computed at multiple post-stimulus time points. The time-course of the R2 function showed a significantly slower processing in older observers starting around 120 ms after stimulus onset. This age-related delay increased over time to reach a maximum around 190 ms, at which latency younger observers had around 50 ms time lead over older observers. Conclusion: Using a component-free ERP analysis that provides a precise timing of the visual system sensitivity to image structure, the current study demonstrates that older observers accumulate face information more slowly than younger subjects. Additionally, the N170 appears to be less face-sensitive in older observers

Efficient control of atmospheric sulfate production based on three formation regimes

The formation of sulfate (SO₄²⁻) in the atmosphere is linked chemically to its direct precursor, sulfur dioxide (SO₂), through several key oxidation paths for which nitrogen oxides or NO_x (NO and NO₂) play essential roles. Here we present a coherent description of the dependence of SO₄²⁻ formation on SO₂ and NO_x under haze-fog conditions, in which fog events are accompanied by high aerosol loadings and fog-water pH in the range of 4.7–6.9. Three SO₄²⁻ formation regimes emerge as defined by the role played by NO_x. In the low-NO_x regime, NO_x act as catalyst for HO_x, which is a major oxidant for SO₂, whereas in the high-NO_x regime, NO₂ is a sink for HO_x. Moreover, at highly elevated NO_x levels, a so-called NO₂-oxidant regime exists in which aqueous NO₂ serves as the dominant oxidant of SO₂. This regime also exists under clean fog conditions but is less prominent. Sensitivity calculations using an emission-driven box model show that the reduction of SO₄²⁻ is comparably sensitive to the reduction of SO₂ and NO_x emissions in the NO₂-oxidant regime, suggesting a co-reduction strategy. Formation of SO₄²⁻ is relatively insensitive to NO_x reduction in the low-NO_x regime, whereas reduction of NO_x actually leads to increased SO₄²⁻ production in the intermediate high-NO_x regime

Training compliance control yields improvements in drawing as a function of beery scores

Many children have difficulty producing movements well enough to improve in sensori-motor learning. Previously, we developed a training method that supports active movement generation to allow improvement at a 3D tracing task requiring good compliance control. Here, we tested 7–8 year old children from several 2nd grade classrooms to determine whether 3D tracing performance could be predicted using the Beery VMI. We also examined whether 3D tracing training lead to improvements in drawing. Baseline testing included Beery, a drawing task on a tablet computer, and 3D tracing. We found that baseline performance in 3D tracing and drawing co-varied with the visual perception (VP) component of the Beery. Differences in 3D tracing between children scoring low versus high on the Beery VP replicated differences previously found between children with and without motor impairments, as did post-training performance that eliminated these differences. Drawing improved as a result of training in the 3D tracing task. The training method improved drawing and reduced differences predicted by Beery scores

Risk of acute kidney injury and survival in patients treated with Metformin:an observational cohort study

Background: Whether metformin precipitates lactic acidosis in patients with chronic kidney disease (CKD) remains under debate. We examined whether metformin use was associated with an increased risk of acute kidney injury (AKI) as a proxy for lactic acidosis and whether survival among those with AKI varied by metformin exposure. Methods: All individuals with type 2 diabetes and available prescribing data between 2004 and 2013 in Tayside, Scotland were included. The electronic health record for diabetes which includes issued prescriptions was linked to laboratory biochemistry, hospital admission, death register and Scottish Renal Registry data. AKI events were defined using the Kidney Disease Improving Global Outcomes criteria with a rise in serum creatinine of at least 26.5 μmol/l or a rise of greater than 150% from baseline for all hospital admissions. Cox Regression Analyses were used to examine whether person-time periods in which current metformin exposure occurred were associated with an increased rate of first AKI compared to unexposed periods. Cox regression was also used to compare 28 day survival rates following first AKI events in those exposed to metformin versus those not exposed. Results: Twenty-five thousand one-hundred fourty-eight patients were included with a total person-time of 126,904 person years. 4944 (19.7%) people had at least one episode of AKI during the study period. There were 32.4 cases of first AKI/1000pyrs in current metformin exposed person-time periods compared to 44.9 cases/1000pyrs in unexposed periods. After adjustment for age, sex, diabetes duration, calendar time, number of diabetes drugs and baseline renal function, current metformin use was not associated with AKI incidence, HR 0.94 (95% CI 0.87, 1.02, p = 0.15). Among those with incident AKI, being on metformin at admission was associated with a higher rate of survival at 28 days (HR 0.81, 95% CI 0.69, 0.94, p = 0.006) even after adjustment for age, sex, pre-admission eGFR, HbA1c and diabetes duration. Conclusions: Contrary to common perceptions, we found no evidence that metformin increases incidence of AKI and was associated with higher 28 day survival following incident AKI

Type 2 diabetes, socioeconomic status and life expectancy in Scotland (2012-2014):a population-based observational study

Aims/hypothesis: The aim of this study was to assess the role of socioeconomic status (SES) in the associations between type 2 diabetes and life expectancy in a complete national population. Methods: An observational population-based cohort study was performed using the Scottish Care Information – Diabetes database. Age-specific life expectancy (stratified by SES) was calculated for all individuals with type 2 diabetes in the age range 40–89 during the period 2012–2014, and for the remaining population of Scotland aged 40–89 without type 2 diabetes. Differences in life expectancy between the two groups were calculated. Results: Results were based on 272,597 individuals with type 2 diabetes and 2.75 million people without type 2 diabetes (total for 2013, the middle calendar year of the study period). With the exception of deprived men aged 80–89, life expectancy in people with type 2 diabetes was significantly reduced (relative to the type 2 diabetes-free population) at all ages and levels of SES. Differences in life expectancy ranged from −5.5 years (95% CI −6.2, −4.8) for women aged 40–44 in the second most-deprived quintile of SES, to 0.1 years (95% CI −0.2, 0.4) for men aged 85–89 in the most-deprived quintile of SES. Observed life-expectancy deficits in those with type 2 diabetes were generally greater in women than in men. Conclusions/interpretation: Type 2 diabetes is associated with reduced life expectancy at almost all ages and levels of SES. Elimination of life-expectancy deficits in individuals with type 2 diabetes will require prevention and management strategies targeted at all social strata (not just deprived groups)

Diabetes MILES - Australia (Management and Impact for Long-Term Empowerment and Success) : methods and sample characteristics of a national survey of the psychological aspects of living with type 1 or type 2 diabetes in Australian adults

Background Successful management of diabetes requires attention to the behavioural, psychological and social aspects of this progressive condition. The Diabetes MILES (Management and Impact for Long-term Empowerment and Success) Study is an international collaborative. Diabetes MILES-Australia, the first Diabetes MILES initiative to be undertaken, was a national survey of adults living with type 1 or type 2 diabetes in Australia. The aim of this study was to gather data that will provide insights into how Australians manage their diabetes, the support they receive and the impact of diabetes on their lives, as well as to use the data to validate new diabetes outcome measures.Methods The survey was designed to include a core set of self-report measures, as well as modules specific to diabetes type or management regimens. Other measures or items were included in only half of the surveys. Cognitive debriefing interviews with 20 participants ensured the survey content was relevant and easily understood. In July 2011, the survey was posted to 15,000 adults (aged 18-70 years) with type 1 or type 2 diabetes selected randomly from the National Diabetes Services Scheme (NDSS) database. An online version of the survey was advertised nationally. A total of 3,338 eligible Australians took part; most (70.4%) completed the postal survey. Respondents of both diabetes types and genders, and of all ages, were adequately represented in both the postal and online survey sub-samples. More people with type 2 diabetes than type 1 diabetes took part in Diabetes MILES-Australia (58.8% versus 41.2%). Most respondents spoke English as their main language, were married/in a de facto relationship, had at least a high school education, were occupied in paid work, had an annual household income &gt; $AUS40,000, and lived in metropolitan areas.Discussion A potential limitation of the study is the under-representation of respondents from culturally and linguistically diverse backgrounds (including Aboriginal and Torres Strait Islander origin). Diabetes MILES-Australia represents a major achievement in the study of diabetes in Australia, where for the first time, the focus is on psychosocial and behavioural aspects of this condition at a national level. <br /

Diabetes MILES – The Netherlands: rationale, design and sample characteristics of a national survey examining the psychosocial aspects of living with diabetes in Dutch adults

Background : As the number of people with diabetes is increasing rapidly worldwide, a more thorough understanding of the psychosocial aspects of living with this condition has become an important health care priority. While our knowledge has grown substantially over the past two decades with respect to the physical, emotional and social difficulties that people with diabetes may encounter, many important issues remain to be elucidated. Under the umbrella of the Diabetes MILES (Management and Impact for Long-term Empowerment and Success) Study International Collaborative, Diabetes MILES &ndash; The Netherlands aims to examine how Dutch adults with diabetes manage their condition and how it affects their lives. Topics of special interest in Diabetes MILES - The Netherlands include subtypes of depression, Type D personality, mindfulness, sleep and sexual functioning. Methods/design : Diabetes MILES &ndash; The Netherlands was designed as a national online observational study among adults with diabetes. In addition to a main set of self-report measures, the survey consisted of five complementary modules to which participants were allocated randomly. From September to October 2011, a total of 3,960 individuals with diabetes (40% type 1, 53% type 2) completed the battery of questionnaires covering a broad range of topics, including general health, self-management, emotional well-being and contact with health care providers. People with self-reported type 1 diabetes (specifically those on insulin pump therapy) were over-represented, as were those using insulin among respondents with self-reported type 2 diabetes. People from ethnic minorities were under-represented. The sex distribution was fairly equal in the total sample, participants spanned a broad age range (19&ndash;90 years), and diabetes duration ranged from recent diagnosis to living with the condition for over fifty years. Discussion : The Diabetes MILES Study enables detailed investigation of the psychosocial aspects of living with diabetes and an opportunity to put these findings in an international context. With several papers planned resulting from a pooled Australian-Dutch dataset and data collections planned in other countries, the Diabetes MILES Study International Collaborative will contribute substantially to identifying potentially unmet needs of those living with diabetes and to inform clinical research and care across the globe. <br /

Patterns of childhood body mass index (BMI), overweight and obesity in South Asian and black participants in the English National child measurement programme: effect of applying BMI adjustments standardising for ethnic differences in BMI-body fatness associations.

BACKGROUND: The National Child Measurement Programme (NCMP) records weight and height and assesses overweight-obesity patterns in English children using body mass index (BMI), which tends to underestimate body fatness in South Asian children and overestimate body fatness in Black children of presumed African ethnicity. Using BMI adjustments to ensure that adjusted BMI was similarly related to body fatness in South Asian, Black and White children, we reassessed population overweight and obesity patterns in these ethnic groups in NCMP. METHODS: Analyses were based on 2012-2013 NCMP data in 582 899 children aged 4-5 years and 485 362 children aged 10-11 years. Standard centile-based approaches defined weight status in each age group before and after applying BMI adjustments for English South Asian and Black children derived from previous studies using the deuterium dilution method. FINDINGS: Among White children, overweight-obesity prevalences (boys, girls) were 23% and 21%, respectively, in 4-5 year olds and 33% and 30%, respectively, in 10-11 year olds. Before adjustment, South Asian children had lower overweight-obesity prevalences at 4-5 years (19%, 19%) and slightly higher prevalences at 10-11 years (42%, 34%), whereas Black children had higher overweight-obesity prevalences both at 4-5 years (31%, 29%) and 10-11 years (42%, 45%). Following adjustment, overweight-obesity prevalences were markedly higher in South Asian children both at 4-5 years (39%, 35%) and at 10-11 years (52%, 44%), whereas Black children had lower prevalences at 4-5 years (11%, 12%); at 10-11 years, prevalences were slightly lower in boys (32%) but higher in girls (35%). INTERPRETATION: BMI adjustments revealed extremely high overweight-obesity prevalences among South Asian children in England, which were not apparent in unadjusted data. In contrast, after adjustment, Black children had lower overweight-obesity prevalences except among older girls. FUNDING: British Heart Foundation, NIHR CLAHRC (South London), NIHR CLAHRC (North Thames)