Decadal changes in the mid-depth water mass dynamic of the Northeastern Atlantic margin (Bay of Biscay)

The lithium/magnesium (Li/Mg) molar ratios, radiocarbon measurements (?14C) and Nd-isotopic composition (eNd) of the aragonite skeleton of a branching cold-water coral (CWC) species Madrepora oculata collected alive in the Bay of Biscay at ~691 m water depth were investigated to reconstruct a robust record of the mid-depth water mass dynamics between 1950 and 1990 AD. Temperature estimates based on the skeletons Li/Mg molar ratios reveal small decadal changes of about 1 °C at thermocline depth synchronous to and of similar amplitude as surface temperature anomalies. ?14C measurements shows quasi-decadal oscillations of 15‰ around pre-bomb ?14C average value of -59±6‰ and post-bomb ?14C of -12±6‰, which most likely reflect decadal changes of water mass exchange across the thermocline. The coral eNd values remain in narrow ranges of -11.9 to -10.2, similar to the isotopic composition of East North Atlantic Central Water, but show highest values in the late 1950s, and early 1960s, 1970s, and 1980s. The punctuated changes of the coral Nd-isotopic composition may thus reflect periods of particular enhanced advection of temperate intermediate water (mid-depth Subpolar Gyre/Mediterranean Sea Water). Altogether, our robust multi-proxy record provides new evidence that Northern Hemisphere atmospheric variability (such as, North Atlantic Oscillation and East Atlantic pattern) drives changes not only in the thermocline but also in the mid-depth water-mass advection patterns in the Northeastern Atlantic margin. However, the interannual variability of our record remains to be tested

Transgenic overexpression of miR-133a in skeletal muscle

<p>Abstract</p> <p>Background</p> <p>MicroRNAs (miRNAs) are a class of non-coding regulatory RNAs of ~22 nucleotides in length. miRNAs regulate gene expression post-transcriptionally, primarily by associating with the 3' untranslated region (UTR) of their regulatory target mRNAs. Recent work has begun to reveal roles for miRNAs in a wide range of biological processes, including cell proliferation, differentiation and apoptosis. Many miRNAs are expressed in cardiac and skeletal muscle, and dysregulated miRNA expression has been correlated with muscle-related disorders. We have previously reported that the expression of muscle-specific miR-1 and miR-133 is induced during skeletal muscle differentiation and miR-1 and miR-133 play central regulatory roles in myoblast proliferation and differentiation in vitro.</p> <p>Methods</p> <p>In this study, we measured the expression of miRNAs in the skeletal muscle of mdx mice, an animal model for human muscular dystrophy. We also generated transgenic mice to overexpress miR-133a in skeletal muscle.</p> <p>Results</p> <p>We examined the expression of miRNAs in the skeletal muscle of <it>mdx </it>mice. We found that the expression of muscle miRNAs, including miR-1a, miR-133a and miR-206, was up-regulated in the skeletal muscle of <it>mdx </it>mice. In order to further investigate the function of miR-133a in skeletal muscle in vivo, we have created several independent transgenic founder lines. Surprisingly, skeletal muscle development and function appear to be unaffected in miR-133a transgenic mice.</p> <p>Conclusions</p> <p>Our results indicate that miR-133a is dispensable for the normal development and function of skeletal muscle.</p

Defining Smallness for Gestational Age in the Early Years of the Danish Medical Birth Registry

Background: Being born small for gestational age (SGA) is associated with decreased insulin sensitivity and increased blood pressure in childhood, but the association with clinical disease in early adulthood is less certain. The Danish Medical Birth Registry has registered all births in Denmark since 1973, but due to variable data quality, data is most often used only from 1981 onwards, and birth registers in other countries may have similar problems for the early years. We wanted to examine whether the data can be used for identification of children born SGA and used in future research. Methodology/Principal Findings: All persons born between 1974 and 1996 were identified in the Danish Medical Birth Registry (n = 1.704.890). Immigrants and children without data on gestational age and birth weight were excluded, and a total of 1.348.106 children were included in the analysis. The difference between the different variables used in the history of the registry were examined, and the quality of data in the birth registry from 1974-1981 was examined and compared to subsequent years. Data on birth weight and gestational age in the early years of the registry is inconsistent, and the identification of children born SGA is inaccurate, with 49 % false-positives. The biggest source of error is due to the rough and inaccurate intervals used for gestational age. By using –3 standard deviations as a cut-off for the identification of children born SGA, the number of false-positives was reduced to 9%, while the amount of false-negatives were increased. Conclusion: Choosing –3 standard deviations for identifying children born SGA is a viable, though not optimal solution fo

A randomised clinical trial on a comprehensive geriatric assessment and intensive home follow-up after hospital discharge: the Transitional Care Bridge

<p>Abstract</p> <p>Background</p> <p>Older patients are at high risk for poor outcomes after acute hospital admission. The mortality rate in these patients is approximately 20%, whereas 30% of the survivors decline in their level of activities of daily living (ADL) functioning three months after hospital discharge. Most diseases and geriatric conditions that contribute to poor outcomes could be subject to pro-active intervention; not only during hospitalization, but also after discharge. This paper presents the design of a randomised controlled clinical trial concerning the effect of a pro-active, multi-component, nurse-led transitional care program following patients for six months after hospital admission.</p> <p>Methods/Design</p> <p>Three hospitals in the Netherlands will participate in the multi-centre, double-blind, randomised clinical trial comparing a pro-active multi-component nurse-led transitional care program to usual care after discharge. All patients acutely admitted to the Department of Internal Medicine who are 65 years and older, hospitalised for at least 48 hours and are at risk for functional decline are invited to participate in the study. All patients will receive integrated geriatric care by a geriatric consultation team during hospital admission. Randomization, which will be stratified by study site and cognitive impairment, will be conducted during admission. The intervention group will receive the transitional care bridge program, consisting of a handover moment with a community care Care Nurse (CN) during hospital admission and five home visits after discharge. The control group will receive 'care as usual' after discharge. The main outcome is the level of ADL functioning six months after discharge compared to premorbid functioning measured with the Katz ADL index. Secondary outcomes include; survival, cognitive functioning, quality of life, and health care utilization, satisfaction of the patient and primary care giver with the transitional care bridge program. All outcomes will be measured at three, six and twelve months after discharge. Approximately 674 patients will be enrolled to either the intervention or control group.</p> <p>Discussion</p> <p>The study will provide new knowledge on a combined intervention of integrated care during hospital admission, a proactive handover moment before discharge and intensive home visits after discharge.</p> <p>Trial registration</p> <p><b>Trial registration number: NTR 2384</b></p

MSH3 polymorphisms and protein levels affect CAG repeat instability in huntington's disease mice

Expansions of trinucleotide CAG/CTG repeats in somatic tissues are thought to contribute to ongoing disease progression through an affected individual's life with Huntington's disease or myotonic dystrophy. Broad ranges of repeat instability arise between individuals with expanded repeats, suggesting the existence of modifiers of repeat instability. Mice with expanded CAG/CTG repeats show variable levels of instability depending upon mouse strain. However, to date the genetic modifiers underlying these differences have not been identified. We show that in liver and striatum the R6/1 Huntington's disease (HD) (CAG)~100 transgene, when present in a congenic C57BL/6J (B6) background, incurred expansion-biased repeat mutations, whereas the repeat was stable in a congenic BALB/cByJ (CBy) background. Reciprocal congenic mice revealed the Msh3 gene as the determinant for the differences in repeat instability. Expansion bias was observed in congenic mice homozygous for the B6 Msh3 gene on a CBy background, while the CAG tract was stabilized in congenics homozygous for the CBy Msh3 gene on a B6 background. The CAG stabilization was as dramatic as genetic deficiency of Msh2. The B6 and CBy Msh3 genes had identical promoters but differed in coding regions and showed strikingly different protein levels. B6 MSH3 variant protein is highly expressed and associated with CAG expansions, while the CBy MSH3 variant protein is expressed at barely detectable levels, associating with CAG stability. The DHFR protein, which is divergently transcribed from a promoter shared by the Msh3 gene, did not show varied levels between mouse strains. Thus, naturally occurring MSH3 protein polymorphisms are modifiers of CAG repeat instability, likely through variable MSH3 protein stability. Since evidence supports that somatic CAG instability is a modifier and predictor of disease, our data are consistent with the hypothesis that variable levels of CAG instability associated with polymorphisms of DNA repair genes may have prognostic implications for various repeat-associated diseases

Evaluation design of a reactivation care program to prevent functional loss in hospitalised elderly: A cohort study including a randomised controlled trial

Background: Elderly persons admitted to the hospital are at risk for hospital related functional loss. This evaluation aims to compare the effects of different levels of (integrated) health intervention care programs on preventing hospital related functional loss among elderly patients by comparing a new intervention program to two usual care progra

Exposure assessment of process-related contaminants in food by biomarker monitoring

Exposure assessment is a fundamental part of the risk assessment paradigm, but can often present a number of challenges and uncertainties. This is especially the case for process contaminants formed during the processing, e.g. heating of food, since they are in part highly reactive and/or volatile, thus making exposure assessment by analysing contents in food unreliable. New approaches are therefore required to accurately assess consumer exposure and thus better inform the risk assessment. Such novel approaches may include the use of biomarkers, physiologically based kinetic (PBK) modelling-facilitated reverse dosimetry, and/or duplicate diet studies. This review focuses on the state of the art with respect to the use of biomarkers of exposure for the process contaminants acrylamide, 3-MCPD esters, glycidyl esters, furan and acrolein. From the overview presented, it becomes clear that the field of assessing human exposure to process-related contaminants in food by biomarker monitoring is promising and strongly developing. The current state of the art as well as the existing data gaps and challenges for the future were defined. They include (1) using PBK modelling and duplicate diet studies to establish, preferably in humans, correlations between external exposure and biomarkers; (2) elucidation of the possible endogenous formation of the process-related contaminants and the resulting biomarker levels; (3) the influence of inter-individual variations and how to include that in the biomarker-based exposure predictions; (4) the correction for confounding factors; (5) the value of the different biomarkers in relation to exposure scenario’s and risk assessment, and (6) the possibilities of novel methodologies. In spite of these challenges it can be concluded that biomarker-based exposure assessment provides a unique opportunity to more accurately assess consumer exposure to process-related contaminants in food and thus to better inform risk assessment

Worldwide trends in underweight and obesity from 1990 to 2022: a pooled analysis of 3663 population-representative studies with 222 million children, adolescents, and adults

Background Underweight and obesity are associated with adverse health outcomes throughout the life course. We estimated the individual and combined prevalence of underweight or thinness and obesity, and their changes, from 1990 to 2022 for adults and school-aged children and adolescents in 200 countries and territories. Methods We used data from 3663 population-based studies with 222 million participants that measured height and weight in representative samples of the general population. We used a Bayesian hierarchical model to estimate trends in the prevalence of different BMI categories, separately for adults (age ≥20 years) and school-aged children and adolescents (age 5–19 years), from 1990 to 2022 for 200 countries and territories. For adults, we report the individual and combined prevalence of underweight (BMI &lt;18·5 kg/m2) and obesity (BMI ≥30 kg/m2). For school&#x2;aged children and adolescents, we report thinness (BMI &lt;2 SD below the median of the WHO growth reference) and obesity (BMI &gt;2 SD above the median). Findings From 1990 to 2022, the combined prevalence of underweight and obesity in adults decreased in 11 countries (6%) for women and 17 (9%) for men with a posterior probability of at least 0·80 that the observed changes were true decreases. The combined prevalence increased in 162 countries (81%) for women and 140 countries (70%) for men with a posterior probability of at least 0·80. In 2022, the combined prevalence of underweight and obesity was highest in island nations in the Caribbean and Polynesia and Micronesia, and countries in the Middle East and north Africa. Obesity prevalence was higher than underweight with posterior probability of at least 0·80 in 177 countries (89%) for women and 145 (73%) for men in 2022, whereas the converse was true in 16 countries (8%) for women, and 39 (20%) for men. From 1990 to 2022, the combined prevalence of thinness and obesity decreased among girls in five countries (3%) and among boys in 15 countries (8%) with a posterior probability of at least 0·80, and increased among girls in 140 countries (70%) and boys in 137 countries (69%) with a posterior probability of at least 0·80. The countries with highest combined prevalence of thinness and obesity in school-aged children and adolescents in 2022 were in Polynesia and Micronesia and the Caribbean for both sexes, and Chile and Qatar for boys. Combined prevalence was also high in some countries in south Asia, such as India and Pakistan, where thinness remained prevalent despite having declined. In 2022, obesity in school-aged children and adolescents was more prevalent than thinness with a posterior probability of at least 0·80 among girls in 133 countries (67%) and boys in 125 countries (63%), whereas the converse was true in 35 countries (18%) and 42 countries (21%), respectively. In almost all countries for both adults and school-aged children and adolescents, the increases in double burden were driven by increases in obesity, and decreases in double burden by declining underweight or thinness. Interpretation The combined burden of underweight and obesity has increased in most countries, driven by an increase in obesity, while underweight and thinness remain prevalent in south Asia and parts of Africa. A healthy nutrition transition that enhances access to nutritious foods is needed to address the remaining burden of underweight while curbing and reversing the increase in obesit