Association between carotid intima-media thickness and bone mineral density: A cross-sectional study in Vietnamese men and women aged 50 years and older

© 2019 Author(s). Objectives The association between osteoporosis and atherosclerosis remains controversial. We sought to define the relationship between carotid intima-media thickness and bone mineral density (BMD) in individuals of Vietnamese background. Design and setting Cross-sectional study in Ho Chi Minh City, Vietnam. Participants The study involved 1460 individuals (559 men) aged 50 years and older (average age 59 years) who were randomly recruited from the community. Outcome measures BMD at the femoral neck and lumbar spine was measured by dual-energy X-ray absorptiometry (Hologic, Waltham, Massachusetts, USA). Carotid intima-media thickness (cIMT) was measured using a Philips Ultrasonography (HD7XE). The presence of atherosclerotic plaque was ascertained for each individual. The association between cIMT and BMD was analysed by a multiple linear regression model. Results In unadjusted analysis, cIMT was positively associated with femoral neck BMD in men (p=0.005), but not in women (p=0.242). After adjusting for age, smoking, diabetes and hypertension, the association remained statistically significant in men (partial R 2 =0.005; p=0.015) but not in women (partial R 2 =0.008; p=0.369). When the analysis was limited to individuals aged 60 years and older, the association between cIMT and BMD was no longer statistically significant. There was no statistically significant association between cIMT and lumbar spine BMD in either men or women. Conclusions In Vietnamese individuals aged 50 years and older, there is a clinically non-significant but statistically significant association between carotid intima-media thickness and BMD in men, not in women

Comparison of two dengue NS1 rapid tests for sensitivity, specificity and relationship to viraemia and antibody responses

<p>Abstract</p> <p>Background</p> <p>Dengue is a major public health problem in tropical and subtropical countries. Rapid and easy diagnosis of dengue can assist patient triage and care-management. The detection of DENV NS1 on rapid lateral flow tests offers a fast route to a presumptive dengue diagnosis but careful evaluations are urgently needed as more and more people use them.</p> <p>Methods</p> <p>The sensitivity and specificity of the Bio-Rad NS1 Ag Strip and SD Dengue Duo (NS1/IgM/IgG) lateral flow rapid tests were evaluated in a panel of plasma samples from 245 Vietnamese patients with RT-PCR confirmed dengue and 47 with other febrile illnesses.</p> <p>Results</p> <p>The NS1 rapid tests had similar diagnostic sensitivities (respectively 61.6% and 62.4%) in confirmed dengue cases but were 100% specific. When IgM/IgG results from the SD Dengue Duo were included in the test interpretation, the sensitivity improved significantly from 62.4% with NS1 alone to 75.5% when NS1 and/or IgM was positive and 83.7% when NS1 and/or IgM and/or IgG was positive. Both NS1 assays were significantly more sensitive for primary than secondary dengue. NS1 positivity was associated with the underlying viraemia as NS1-positive samples had a significantly higher viraemia than NS1-negative samples.</p> <p>Conclusions</p> <p>These data suggest that the NS1 test component of these assays are highly specific and have similar levels of sensitivity. The IgM parameter in the SD Duo test improved overall test sensitivity without compromising specificity. The SD Dengue Duo lateral flow rapid test deserves further prospective evaluation in dengue endemic settings.</p

Post translational changes to α-synuclein control iron and dopamine trafficking : a concept for neuron vulnerability in Parkinson's disease

Parkinson's disease is a multifactorial neurodegenerative disorder, the aetiology of which remains elusive. The primary clinical feature of progressively impaired motor control is caused by a loss of midbrain substantia nigra dopamine neurons that have a high α-synuclein (α-syn) and iron content. α-Syn is a neuronal protein that is highly modified post-translationally and central to the Lewy body neuropathology of the disease. This review provides an overview of findings on the role post translational modifications to α-syn have in membrane binding and intracellular vesicle trafficking. Furthermore, we propose a concept in which acetylation and phosphorylation of α-syn modulate endocytic import of iron and vesicle transport of dopamine during normal physiology. Disregulated phosphorylation and oxidation of α-syn mediate iron and dopamine dependent oxidative stress through impaired cellular location and increase propensity for α-syn aggregation. The proposition highlights a connection between α-syn, iron and dopamine, three pathological components associated with disease progression in sporadic Parkinson's disease

Gravitational-wave research as an emerging field in the Max Planck Society. The long roots of GEO600 and of the Albert Einstein Institute

On the occasion of the 50th anniversary since the beginning of the search for gravitational waves at the Max Planck Society, and in coincidence with the 25th anniversary of the foundation of the Albert Einstein Institute, we explore the interplay between the renaissance of general relativity and the advent of relativistic astrophysics following the German early involvement in gravitational-wave research, to the point when gravitational-wave detection became established by the appearance of full-scale detectors and international collaborations. On the background of the spectacular astrophysical discoveries of the 1960s and the growing role of relativistic astrophysics, Ludwig Biermann and his collaborators at the Max Planck Institute for Astrophysics in Munich became deeply involved in research related to such new horizons. At the end of the 1960s, Joseph Weber's announcements claiming detection of gravitational waves sparked the decisive entry of this group into the field, in parallel with the appointment of the renowned relativist Juergen Ehlers. The Munich area group of Max Planck institutes provided the fertile ground for acquiring a leading position in the 1970s, facilitating the experimental transition from resonant bars towards laser interferometry and its innovation at increasingly large scales, eventually moving to a dedicated site in Hannover in the early 1990s. The Hannover group emphasized perfecting experimental systems at pilot scales, and never developed a full-sized detector, rather joining the LIGO Scientific Collaboration at the end of the century. In parallel, the Max Planck Institute for Gravitational Physics (Albert Einstein Institute) had been founded in Potsdam, and both sites, in Hannover and Potsdam, became a unified entity in the early 2000s and were central contributors to the first detection of gravitational waves in 2015.Comment: 94 pages. Enlarged version including new results from further archival research. A previous version appears as a chapter in the volume The Renaissance of General Relativity in Context, edited by A. Blum, R. Lalli and J. Renn (Boston: Birkhauser, 2020

Allele-specific control of rodent and human lncRNA KMT2E-AS1 promotes hypoxic endothelial pathology in pulmonary hypertension

Hypoxic reprogramming of vasculature relies on genetic, epigenetic, and metabolic circuitry, but the control points are unknown. In pulmonary arterial hypertension (PAH), a disease driven by hypoxia inducible factor (HIF)–dependent vascular dysfunction, HIF-2α promoted expression of neighboring genes, long noncoding RNA (lncRNA) histone lysine N-methyltransferase 2E-antisense 1 (KMT2E-AS1) and histone lysine N-methyltransferase 2E (KMT2E). KMT2E-AS1 stabilized KMT2E protein to increase epigenetic histone 3 lysine 4 trimethylation (H3K4me3), driving HIF-2α–dependent metabolic and pathogenic endothelial activity. This lncRNA axis also increased HIF-2α expression across epigenetic, transcriptional, and posttranscriptional contexts, thus promoting a positive feedback loop to further augment HIF-2α activity. We identified a genetic association between rs73184087, a single-nucleotide variant (SNV) within a KMT2E intron, and disease risk in PAH discovery and replication patient cohorts and in a global meta-analysis. This SNV displayed allele (G)–specific association with HIF-2α, engaged in long-range chromatin interactions, and induced the lncRNA-KMT2E tandem in hypoxic (G/G) cells. In vivo, KMT2E-AS1 deficiency protected against PAH in mice, as did pharmacologic inhibition of histone methylation in rats. Conversely, forced lncRNA expression promoted more severe PH. Thus, the KMT2E-AS1/KMT2E pair orchestrates across convergent multi-ome landscapes to mediate HIF-2α pathobiology and represents a key clinical target in pulmonary hypertension

Evaluating the relationship between amyloid-β and α-synuclein phosphorylated at Ser129 in dementia with Lewy bodies and Parkinson’s disease

INTRODUCTION: Lewy body and Alzheimer-type pathologies often co-exist. Several studies suggest a synergistic relationship between amyloid-β (Aβ) and α-synuclein (α-syn) accumulation. We have explored the relationship between Aβ accumulation and the phosphorylation of α-syn at serine-129 (pSer129 α-syn), in post-mortem human brain tissue and in SH-SY5Y neuroblastoma cells transfected to overexpress human α-syn. METHODS: We measured levels of Aβ40, Aβ42, α-syn and pSer129 α-syn by sandwich enzyme-linked immunosorbent assay, in soluble and insoluble fractions of midfrontal, cingulate and parahippocampal cortex and thalamus, from cases of Parkinson’s disease (PD) with (PDD; n = 12) and without dementia (PDND; n = 23), dementia with Lewy bodies (DLB; n = 10) and age-matched controls (n = 17). We also examined the relationship of these measurements to cognitive decline, as measured by time-to-dementia and the mini-mental state examination (MMSE) score in the PD patients, and to Braak tangle stage. RESULTS: In most brain regions, the concentration of insoluble pSer129 α-syn correlated positively, and soluble pSer129 α-syn negatively, with the levels of soluble and insoluble Aβ. Insoluble pSer129 α-syn also correlated positively with Braak stage. In most regions, the levels of insoluble and soluble Aβ and the proportion of insoluble α-syn that was phosphorylated at Ser129 were significantly higher in the PD and DLB groups than the controls, and higher in the PDD and DLB groups than the PDND brains. In PD, the MMSE score correlated negatively with the level of insoluble pSer129 α-syn. Exposure of SH-SY5Y cells to aggregated Aβ42 significantly increased the proportion of α-syn that was phosphorylated at Ser129 (aggregated Aβ40 exposure had a smaller, non-significant effect). CONCLUSIONS: Together, these data show that the concentration of pSer129 α-syn in brain tissue homogenates is directly related to the level of Aβ and Braak tangle stage, and predicts cognitive status in Lewy body diseases. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13195-014-0077-y) contains supplementary material, which is available to authorized users

Methods for Monitoring Matrix-Induced Autophagy.

A growing body of research demonstrates modulation of autophagy by a variety of matrix constituents, including decorin, endorepellin, and endostatin. These matrix proteins are both pro-autophagic and anti-angiogenic. Here, we detail a series of methods to monitor matrix-induced autophagy and its concurrent effects on angiogenesis. We first discuss cloning and purifying proteoglycan fragment and core proteins in the laboratory and review relevant techniques spanning from cell culture to treatment with these purified proteoglycans in vitro and ex vivo. Further, we cover protocols in monitoring autophagic progression via morphological and microscopic characterization, biochemical western blot analysis, and signaling pathway investigation. Downstream angiogenic effects using in vivo approaches are then discussed using wild-type mice and the GFP-LC3 transgenic mouse model. Finally, we explore matrix-induced mitophagy via monitoring changes in mitochondrial DNA and permeability

Exploring ligand recognition and ion flow in comparative models of the human GABA type A receptor.

We present two comparative models of the GABA(A) receptor. Model 1 is based on the 4-A resolution structure of the nicotinic acetylcholine receptor from Torpedo marmorata and represents the unliganded receptor. Two agonists, GABA and muscimol, two benzodiazepines, flunitrazepam and alprazolam, together with the general anaesthetic halothane, have been docked to this model. The ion flow is also explored in model 1 by evaluating the interaction energy of a chloride ion as it traverses the extracellular, transmembrane and intracellular domains of the protein. Model 2 differs from model 1 only in the extracellular domain and represents the liganded receptor. Comparison between the two models not only allows us to explore commonalities and differences with comparative models of the nicotinic acetylcholine receptor, but also suggests possible protein sub-domain interactions with the GABA(A) receptor not previously addressed

Mehrwerte auf Basis digitaler Kassenzettel: eine verbraucherinformatische Studie

Die Digitalisierung aller Lebenswelten wird das Kauf- und Konsumverhalten von Verbrauchern stark ändern. Es zeichnet sich ab, dass Zukunftsszenarien des Smart Shopping, Smart Kitchen und Smart Cooking zunehmend real werden und sich immer stärker verzahnen. Zurzeit finden sich z. B. Bestrebungen zum digitalen Kassenzettel. Der Beitrag zeigt, dass Verbraucher sich hierdurch eine Reihe von Mehrwerten erhoffen, z. B. dass sie eine höhere Transparenz ermöglichen, indem sie Zusatzinformationen zu den Produkten bereitstellen. Ebenfalls sollen die Informationen genutzt werden, Rezeptvorschläge zu den gekauften, im Haus befindlichen Waren sowie Auskunft über den Zustand der Waren bereitzustellen. Ein weiterer Bereich stellt eine bessere Kosten- und Ernährungskontrolle dar, indem die Daten des Kassenzettels automatisch in digitale Haushaltsbücher und Ernährungs- bzw. Fitness-Apps übertragen werden können