Cerebral Hypoxia and Ischemia in the Pathogenesis of Dementia after Stroke

While it has been reported that ischemic stroke significantly increases the risk of delayed dementia,1,2 the underlying mechanisms are not well understood. Hypoxic and ischemic (HI) injury resulting from cerebral hypoperfusion due to systemic illness has been proposed as a pathogenic mechanism in certain subgroups of patients.1,3 Thus, the aim of this study was to investigate whether cerebral HI injury resulting from certain systemic illnesses (e.g., cardiac arrhythmias, cardiac failure, pneumonia, seizures, sepsis) would be an independent risk factor for the development of incident dementia after ischemic stroke

Longitudinal relationships between caloric expenditure and gray matter in the cardiovascular health study

Background: Physical activity (PA) can be neuroprotective and reduce the risk for Alzheimer’s disease (AD). In assessing physical activity, caloric expenditure is a proxy marker reflecting the sum total of multiple physical activity types conducted by an individual. Objective:To assess caloric expenditure, as a proxy marker of PA, as a predictive measure of gray matter (GM) volumes in the normal and cognitively impaired elderly persons. Methods: All subjects in this study were recruited from the Institutional Review Board approved Cardiovascular Health Study (CHS), a multisite population-based longitudinal study in persons aged 65 and older. We analyzed a sub-sample of CHS participants 876 subjects (mean age 78.3, 57.5% F, 42.5% M) who had i) energy output assessed as kilocalories (kcal) per week using the standardized Minnesota Leisure-Time Activities questionnaire, ii) cognitive assessments for clinical classification of normal cognition, mild cognitive impairment (MCI), and AD, and iii) volumetric MR imaging of the brain. Voxel-based morphometry modeled the relationship between kcal/week and GM volumes while accounting for standard covariates including head size, age, sex, white matter hyperintensity lesions, MCI or AD status, and site. Multiple comparisons were controlled using a False Discovery Rate of 5 percent. Results: Higher energy output, from a variety of physical activity types, was associated with larger GM volumes in frontal, temporal, and parietal lobes, as well as hippocampus, thalamus, and basal ganglia. High levels of caloric expenditure moderated neurodegeneration-associated volume loss in the precuneus, posterior cingulate, and cerebellar vermis. Conclusion:Increasing energy output from a variety of physical activities is related to larger gray matter volumes in the elderly, regardless of cognitive status.Cyrus A. Raji, David A. Merrill, Harris Eyre, Sravya Mallam, Nare Torosyan, Kirk I. Erickson, Oscar L. Lopez , James T. Becker, Owen T. Carmichael, H. Michael Gach, Paul M. Thompson, W.T. Longstreth, Jr. and Lewis H. Kulle

Delayed gastric emptying and reduced postprandial small bowel water content of equicaloric whole meal bread versus rice meals in healthy subjects: novel MRI insights

BACKGROUND/OBJECTIVES: Postprandial bloating is a common symptom in patients with functional gastrointestinal (GI) diseases. Whole meal bread (WMB) often aggravates such symptoms though the mechanisms are unclear. We used magnetic resonance imaging (MRI) to monitor the intragastric fate of a WMB meal (11% bran) compared to a rice pudding (RP) meal. SUBJECTS/METHODS: 12 healthy volunteers completed this randomised crossover study. They fasted overnight and after an initial MRI scan consumed a glass of orange juice with a 2267 kJ WMB or an equicaloric RP meal. Subjects underwent serial MRI scans every 45 min up to 270 min to assess gastric volumes and small bowel water content and completed a GI symptom questionnaire. RESULTS: The MRI intragastric appearance of the two meals was markedly different. The WMB meal formed a homogeneous dark bolus with brighter liquid signal surrounding it. The RP meal separated into an upper, liquid layer and a lower particulate layer allowing more rapid emptying of the liquid compared to solid phase (sieving). The WMB meal had longer gastric half emptying times (132±8 min) compared to the RP meal (104±7 min), P<0.008. The WMB meal was associated with markedly reduced MRI-visible small bowel free mobile water content compared to the RP meal, P<0.0001. CONCLUSIONS: WMB bread forms a homogeneous bolus in the stomach which inhibits gastric sieving and hence empties slower than the equicaloric rice meal. These properties may explain why wheat causes postprandial bloating and could be exploited to design foods which prolong satiation

Genetic risk factors for ischaemic stroke and its subtypes (the METASTROKE Collaboration): a meta-analysis of genome-wide association studies

&lt;p&gt;Background - Various genome-wide association studies (GWAS) have been done in ischaemic stroke, identifying a few loci associated with the disease, but sample sizes have been 3500 cases or less. We established the METASTROKE collaboration with the aim of validating associations from previous GWAS and identifying novel genetic associations through meta-analysis of GWAS datasets for ischaemic stroke and its subtypes.&lt;/p&gt; &lt;p&gt;Methods - We meta-analysed data from 15 ischaemic stroke cohorts with a total of 12 389 individuals with ischaemic stroke and 62 004 controls, all of European ancestry. For the associations reaching genome-wide significance in METASTROKE, we did a further analysis, conditioning on the lead single nucleotide polymorphism in every associated region. Replication of novel suggestive signals was done in 13 347 cases and 29 083 controls.&lt;/p&gt; &lt;p&gt;Findings - We verified previous associations for cardioembolic stroke near PITX2 (p=2·8×10−16) and ZFHX3 (p=2·28×10−8), and for large-vessel stroke at a 9p21 locus (p=3·32×10−5) and HDAC9 (p=2·03×10−12). Additionally, we verified that all associations were subtype specific. Conditional analysis in the three regions for which the associations reached genome-wide significance (PITX2, ZFHX3, and HDAC9) indicated that all the signal in each region could be attributed to one risk haplotype. We also identified 12 potentially novel loci at p&#60;5×10−6. However, we were unable to replicate any of these novel associations in the replication cohort.&lt;/p&gt; &lt;p&gt;Interpretation - Our results show that, although genetic variants can be detected in patients with ischaemic stroke when compared with controls, all associations we were able to confirm are specific to a stroke subtype. This finding has two implications. First, to maximise success of genetic studies in ischaemic stroke, detailed stroke subtyping is required. Second, different genetic pathophysiological mechanisms seem to be associated with different stroke subtypes.&lt;/p&gt

Genetic determinants of cortical structure (thickness, surface area and volumes) among disease free adults in the CHARGE Consortium

Cortical thickness, surface area and volumes (MRI cortical measures) vary with age and cognitive function, and in neurological and psychiatric diseases. We examined heritability, genetic correlations and genome-wide associations of cortical measures across the whole cortex, and in 34 anatomically predefined regions. Our discovery sample comprised 22,824 individuals from 20 cohorts within the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) consortium and the United Kingdom Biobank. Significant associations were replicated in the Enhancing Neuroimaging Genetics through Meta-analysis (ENIGMA) consortium, and their biological implications explored using bioinformatic annotation and pathway analyses. We identified genetic heterogeneity between cortical measures and brain regions, and 160 genome-wide significant associations pointing to wnt/β-catenin, TGF-β and sonic hedgehog pathways. There was enrichment for genes involved in anthropometric traits, hindbrain development, vascular and neurodegenerative disease and psychiatric conditions. These data are a rich resource for studies of the biological mechanisms behind cortical development and aging

Ischemic Colitis of the Left Colon in a Diabetic Patient

Diabetes mellitus may affect the gastrointestinal tract possibly as a result of autonomic neuropathy. Here we present a 68-year-old male with non-insulin-dependent diabetes mellitus who presented with prolonged watery diarrhea and in whom imaging studies demonstrated ischemic colitis of the left colon. Resection of the affected colon resulted in sustained disappearance of symptoms

Effectiveness of laxatives in elderly - a cross sectional study in nursing homes

<p>Abstract</p> <p>Background</p> <p>Laxatives are efficient drugs, but the effectiveness has been questioned. In nursing homes, the prevalence of constipation is high and laxatives are commonly used drugs. The aims of the study were to assess the effectiveness of laxative therapy in an everyday setting in Norwegian nursing homes, study differences between treatment regimens and factors associated with normal bowel function.</p> <p>Methods</p> <p>A cross-sectional study. After giving informed consent, residents above 60 years of age using laxatives for functional constipation were included, and their characteristics, medical history, use of drugs and bowel functions were recorded. Normal bowel function was defined as bowel movements from 3 times/week to 3 times/day and stool consistency 3-5 on Bristol Stool Form Scale.</p> <p>Results</p> <p>Out of 647 residents in the nursing homes, 197 were included and 116 (59%) had normal bowel function. The treatment effect did not differ significantly between the laxatives, treatment regimens or expected efficacy of the regimens. The treatment was unsatisfactorily adapted to individual needs. In subjects with normal bowel function, 113 (97%) had persistent complaints; 68 (59.5%), 10 (8.0%), 34 (28.6%) and 26 (22.5%) reported straining, manual manoeuvre to facilitate bowel movements, feeling of incomplete bowel movements, and feeling of anorectal obstruction respectively. Good nutritional status, previous or present cancer disease and anxiety/depression were predictors of normal bowel function.</p> <p>Conclusions</p> <p>Treatment of constipation in nursing homes was unsatisfactory. Nearly all patients with normal stool frequency and consistence had some persistent complaints. Improved nutrition and individualization of the treatment could improve the outcome.</p

Association of coagulation-related and inflammation-related genes and factor VIIc levels with stroke: the Cardiovascular Health Study: Coagulation and inflammation genes and stroke

Thrombosis and inflammation are critical in stroke etiology, but associations of coagulation and inflammation gene variants with stroke, and particularly factor VII levels are inconclusive

Calculating total health service utilisation and costs from routinely collected electronic health records using the example of patients with irritable bowel syndrome before and after their first gastroenterology appointment

INTRODUCTION: Health economic models are increasingly important in funding decisions but most are based on data, which may therefore not represent the general population. We sought to establish the potential of real-world data available within the Clinical Practice Research Datalink (CPRD) and linked Hospital Episode Statistics (HES) to determine comprehensive healthcare utilisation and costs as input variables for economic modelling. METHODS: A cohort of patients with irritable bowel syndrome (IBS) who first saw a gastroenterologist in 2008 or 2009, and with 3 years of data before and after their appointment, was created in the CPRD. Primary care, outpatient, inpatient, prescription and colonoscopy data were extracted from the linked CPRD and HES. The appropriate cost to the NHS was attached to each event. Total and stratified annual healthcare utilisation rates and costs were calculated before and after the gastroenterology appointment with distribution parameters. Absolute differences were calculated with 95 % confidence intervals. RESULTS: Total annual healthcare costs over 3 years increase by £935 (95 % CI £928–941) following a gastroenterology appointment for IBS. We derived utilisation and cost data with parameter distributions stratified by demographics and time. Women, older patients, smokers and patients with greater comorbidity utilised more healthcare resources, which generated higher costs. CONCLUSIONS: These linked datasets provide comprehensive primary and secondary care data for large numbers of patients, which allows stratification of outcomes. It is possible to derive input parameters appropriate for economic models and their distributions directly from the population of interest

New Insights into Blastocystis spp.: A Potential Link with Irritable Bowel Syndrome

International audienceBlastocystis spp. belong to the phylum Stramenopila, a complex and heterogeneous evolutionary assemblage of heterotrophic and photosynthetic protozoa [1]. Interestingly, this is the only stramenopile living in the lower digestive tract of humans, and it also lives in other mammals, birds, reptiles, amphibians, and insects [1]. Even though isolates were reported to be morphologically indistinguishable, an extensive genetic variation among isolates from both humans and animals has been observed. Thirteen subtypes (ST1-ST13), with the first nine being found in humans, have been identified based on genes coding for the small-subunit ribosomal RNA [2]. Preferential repartition of STs exists among animals that appear to constitute the main reservoir for environmental dissemination and human contamination