One of the hallmarks of Alzheimer's disease is the presence of extracellular diffuse and fibrillar plaques predominantly consisting of the amyloid-β (Aβ) peptide. Apolipoprotein E (ApoE) influences ...the deposition of amyloid pathology through affecting the clearance and aggregation of monomeric Aβ in the brain. In addition to influencing Aβ metabolism, increasing evidence suggests that apoE influences microglial function in neurodegenerative diseases. Here, we characterize the impact that apoE has on amyloid pathology and the innate immune response in APPPS1ΔE9 and APPPS1-21 transgenic mice. We report that
deficiency reduced fibrillar plaque deposition, consistent with previous studies. However, fibrillar plaques in
-deficient mice exhibited a striking reduction in plaque compaction. Hyperspectral fluorescent imaging using luminescent conjugated oligothiophenes identified distinct Aβ morphotypes in
-deficient mice. We also observed a significant reduction in fibrillar plaque-associated microgliosis and activated microglial gene expression in
-deficient mice, along with significant increases in dystrophic neurites around fibrillar plaques. Our results suggest that apoE is critical in stimulating the innate immune response to amyloid pathology.
Economic Burden of Obesity: A Systematic Literature Review Tremmel, Maximilian; Gerdtham, Ulf-G; Nilsson, Peter M ...
International journal of environmental research and public health,
04/2017, Letnik:
14, Številka:
4
Journal Article
Recenzirano
Odprti dostop
: The rising prevalence of obesity represents an important public health issue. An assessment of its costs may be useful in providing recommendations for policy and decision makers. This systematic ...review aimed to assess the economic burden of obesity and to identify, measure and describe the different obesity-related diseases included in the selected studies.
: A systematic literature search of studies in the English language was carried out in Medline (PubMed) and Web of Science databases to select cost-of-illness studies calculating the cost of obesity in a study population aged ≥18 years with obesity, as defined by a body mass index of ≥30 kg/m², for the whole selected country. The time frame for the analysis was January 2011 to September 2016.
: The included twenty three studies reported a substantial economic burden of obesity in both developed and developing countries. There was considerable heterogeneity in methodological approaches, target populations, study time frames, and perspectives. This prevents an informative comparison between most of the studies. Specifically, there was great variety in the included obesity-related diseases and complications among the studies.
: There is an urgent need for public health measures to prevent obesity in order to save societal resources. Moreover, international consensus is required on standardized methods to calculate the cost of obesity to improve homogeneity and comparability. This aspect should also be considered when including obesity-related diseases.
Normally, the temperature decreases with altitude, allowing air pollutants to rise and disperse. During inversion episodes, warmer air at higher altitude traps air pollutants at the ground. By ...merging vertical temperature profile data from NASA with pollution monitors and health care records, we show that inversions increase the PM10 levels by 25% and children’s respiratory health problems by 5.5%. Low-income children are particularly affected, and differences in baseline health seem to be a key mediating factor behind the effect of pollution on the SES health gap. Policies that improve dissemination of information on inversion status may hence improve child health, either through private action or via policies that curb emissions during inversion episodes.
Background and aim: Progression to fibrosis in non-alcoholic fatty liver disease (NAFLD) is associated with an increased risk of liver-related events, overall mortality and possibly metabolic ...comorbidities. Our aim was to determine if non-invasive fibrosis scoring systems can predict the future risk of diabetes mellitus, cardiovascular disease (CVD), chronic kidney disease (CKD), liver-related events and overall mortality.
Methods: Patients with biopsy-proven NAFLD 1978 to 2006 were identified from a computerised register in Malmö, Sweden. Medical records were scrutinised in detail to collect data from inclusion to endpoint (death or end of 2016). Non-invasive fibrosis scoring systems (FIB-4-index, NAFLD fibrosis score (NFS), APRI and BARD score) were calculated and the scores classified into three risk categories (low, intermediate and high risk for advanced fibrosis). Chronic kidney disease was evaluated using the CKD-EPI equation.
Results: One hundred and forty-four patients with biopsy-proven NAFLD were included, with a mean age of 53.2 years and a mean follow-up time of 18.8 years. At inclusion, 18% had advanced fibrosis. NFS was the only score that could predict the future risk of all included outcomes with fairly good accuracy (Area-under-ROC curve). Multivariate-adjusted hazard ratios revealed that both the intermediate and high-risk category of FIB-4-index and NFS could significantly predict metabolic outcomes. All four scoring systems significantly predicted overall mortality in the high-risk category.
Conclusions: Non-invasive fibrosis scoring systems, especially NFS and FIB-4-index, can be used to identify patients at risk of future liver-related events, overall mortality, metabolic comorbidities and CKD.
Arterial stiffness is an independent risk factor for cardiovascular morbidity and can be assessed by applanation tonometry by measuring pulse wave velocity (PWV) and augmentation index (AIX) by ...pressure pulse wave analysis (PWA). As an inexpensive and operator independent alternative, photoelectric plethysmography (PPG) has been introduced with analysis of the digital volume pulse wave (DPA) and its second derivatives of wave reflections.
The objective was to investigate the repeatability of arterial stiffness parameters measured by digital pulse wave analysis (DPA) and the associations to applanation tonometry parameters.
112 pregnant and non-pregnant individuals of different ages and genders were examined with SphygmoCor arterial wall tonometry and Meridian DPA finger photoplethysmography. Coefficients of repeatability, Bland-Altman plots, intraclass correlation coefficients and correlations to heart rate (HR) and body height were calculated for DPA variables, and the DPA variables were compared to tonometry variables left ventricular ejection time (LVET), PWV and AIX. No DPA variable showed any systematic measurement error or excellent repeatability, but dicrotic index (DI), dicrotic dilatation index (DDI), cardiac ejection elasticity index (EEI), aging index (AI) and second derivatives of the crude pulse wave curve, b/a and e/a, showed good repeatability. Overall, the correlations to AIX were better than to PWV, with correlations coefficients >0.70 for EEI, AI and b/a. Considering the level of repeatability and the correlations to tonometry, the overall best DPA parameters were EEI, AI and b/a. The two pansystolic time parameters, ejection time compensated (ETc) by DPA and LVET by tonometry, showed a significant but weak correlation.
For estimation of the LV function, ETc, EEI and b/a are suitable, for large artery stiffness EEI, and for small arteries DI and DDI. The only global parameter, AI, showed a high repeatability and the overall best correlations with AIX and PWV.
Abstract
Context
Emerging evidence has related the gut microbiome and circulating metabolites to human obesity. Gut microbiota is responsible for several metabolic functions, and altered plasma ...metabolome might reflect differences in the gut microbiome.
Objective
To identify a plasma metabolite profile associated with body mass index (BMI) in a general population and investigate whether such metabolite profile is associated with distinct composition of the gut microbiota.
Design
Targeted profiling of 48 plasma metabolites was performed in a population of 920 Swedish adults (mean age, 39 years; 53% women) from the ongoing Malmö Offspring Study using targeted liquid chromatography–mass spectrometry. Gut microbiota was analyzed by sequencing the 16S ribosomal RNA gene (V1-V3 region) in fecal samples of 674 study participants.
Results
BMI was associated with 19 metabolites (P < 0.001 for all), of which glutamate provided the strongest direct association (P = 5.2e-53). By orthogonal partial least squares regression, a metabolite principal component predictive of BMI was constructed (PCBMI). In addition to glutamate, PCBMI was dominated by branched-chain amino acids (BCAAs) and related metabolites. Four gut microbiota genera (Blautia, Dorea, Ruminococcus, and SHA-98) were associated with both BMI and PCBMI (P < 8.0e-4 for all). When simultaneously regressing PCBMI and metabolite-associated gut bacteria against BMI, only PCBMI remained statistically significant.
Conclusions
We discovered associations between four gut microbiota genera (Blautia, Dorea, Ruminococcus, and SHA-98) and BMI-predictive plasma metabolites, including glutamate and BCAAs. Thus, these metabolites could be mediators between gut microbiota and obesity, pointing to potential future opportunities for targeting the gut microbiota in prevention of obesity.
We identified metabolites associated with BMI. The BMI-related metabolites were connected to four microbiota genera, suggesting a mediating role of the metabolites in the microbiota–obesity relationship.
Zonulin is considered a biomarker of increased intestinal permeability, and elevated levels have been found in celiac disease. The primary aim of this study was to examine the association between ...serum zonulin levels and gastrointestinal (GI) symptoms, and secondarily, between zonulin levels and anthropometric and metabolic factors. The offspring (
= 363) of the participants of the Malmö Diet and Cancer cardiovascular cohort (MDC-CV) were invited to an anthropometric and clinical examination, where fasting plasma glucose levels were measured. Questionnaires about lifestyle factors and medical history were completed along with the Visual Analog Scale for Irritable Bowel Syndrome (VAS-IBS). Zonulin levels were measured in serum by ELISA. Neither GI symptoms nor GI diseases had any influence on zonulin levels. Higher zonulin levels were associated with higher waist circumference (
= 0.003), diastolic blood pressure (
= 0.003), and glucose levels (
= 0.036). Higher zonulin levels were associated with increased risk of overweight (
< 0.001), obesity (
= 0.047), and hyperlipidemia (
= 0.048). We cannot detect altered zonulin levels among individuals reporting GI symptoms or GI diseases, but higher zonulin levels are associated with higher waist circumference, diastolic blood pressure, fasting glucose, and increased risk of metabolic diseases.
Synucleinopathies are neurodegenerative diseases that are associated with the misfolding and aggregation of α-synuclein, including Parkinson's disease, dementia with Lewy bodies and multiple system ...atrophy
. Clinically, it is challenging to differentiate Parkinson's disease and multiple system atrophy, especially at the early stages of disease
. Aggregates of α-synuclein in distinct synucleinopathies have been proposed to represent different conformational strains of α-synuclein that can self-propagate and spread from cell to cell
. Protein misfolding cyclic amplification (PMCA) is a technique that has previously been used to detect α-synuclein aggregates in samples of cerebrospinal fluid with high sensitivity and specificity
. Here we show that the α-synuclein-PMCA assay can discriminate between samples of cerebrospinal fluid from patients diagnosed with Parkinson's disease and samples from patients with multiple system atrophy, with an overall sensitivity of 95.4%. We used a combination of biochemical, biophysical and biological methods to analyse the product of α-synuclein-PMCA, and found that the characteristics of the α-synuclein aggregates in the cerebrospinal fluid could be used to readily distinguish between Parkinson's disease and multiple system atrophy. We also found that the properties of aggregates that were amplified from the cerebrospinal fluid were similar to those of aggregates that were amplified from the brain. These findings suggest that α-synuclein aggregates that are associated with Parkinson's disease and multiple system atrophy correspond to different conformational strains of α-synuclein, which can be amplified and detected by α-synuclein-PMCA. Our results may help to improve our understanding of the mechanism of α-synuclein misfolding and the structures of the aggregates that are implicated in different synucleinopathies, and may also enable the development of a biochemical assay to discriminate between Parkinson's disease and multiple system atrophy.
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