An eleven-vertex deltahedron with hexacapped trigonal bipyramidal geometry.

International audienceThe first elemental cluster with hexacapped trigonal bipyramidal geometry is revealed in the luminescent undecanuclear silver complex which is stabilized by nine dithiocarbamate ligands and has an interstitial hydride. The hydride position within the Ag(11) cage is confirmed by a DFT investigation

Potassium {4-[(3S,6S,9S)-3,6-dibenzyl-9-isopropyl-4,7,10-trioxo-11–oxa-2,5,8-triazadodecyl]phenyl}trifluoroborate

[[abstract]]The reported compound 4 was synthesized and fully characterized by 1H NMR, 13C NMR, 11B NMR, 19F NMR, and high resolution mass spectrometry.[[booktype]]電子版[[countrycodes]]CH

Efficacy of multidomain interventions to improve physical frailty, depression and cognition: data from cluster- randomized controlled trials

BackgroundFrailty is the pre- eminent exigency of aging. Although frailty- related impairments are preventable, and multidomain interventions appear more effective than unimodal ones, the optimal components remain uncertain.MethodsWe devised multidomain interventions against physical and cognitive decline among prefrail/frail community- dwelling - ¥65- year- olds and evaluated these in complementary cluster- randomized trials of efficacy and participant empowerment. The Efficacy Study compared ~3- monthly telephone consultations vs. 16, 2 h sessions/year comprising communally partaken physical and cognitive training plus nutrition and disease education; the Empowerment Study compared the standard Efficacy Study multidomain intervention (Sessions 1- 10) vs. an enhanced version redesigned to empower and motivate individual participants. Changes from baseline in physical, functional, and cognitive performance were measured after 6 and 12 months in the Efficacy Study and after 6 months in the Empowerment Study, with post- intervention follow- up at 9 months. Primary outcomes are as follows: Cardiovascular Health Study frailty score; gait speed; handgrip strength; and Montreal Cognitive Assessment (MoCA). Secondary outcomes are as follows: instrumental activities of daily living; metabolic equivalent of task (MET); depressed mood (Geriatric Depression Scale- 5 - ¥2); and malnutrition (Mini- Nutritional Assessment short- form - ¤11). Intervention effects were analyzed using a generalized linear mixed model.ResultsEfficacy Study participants (n = 1082, 40 clusters) were 75.1 ± 6.3 years old, 68.7% women, and 64.7% prefrail/frail; analytic clusters: 19 intervention (410/549 completed) vs. 21 control (375/533 completed). Empowerment Study participants (n = 440, 14 clusters) were 75.9 ± 7.1 years old, 83.6% women, and 56.7% prefrail/frail; analytic clusters: seven intervention (209/230 completed) vs. seven control (189/210 completed). The standard and enhanced multidomain interventions both reduced frailty and significantly improved aspects of physical, functional, and cognitive performance, especially among - ¥75- year- olds. Standard multidomain intervention decreased depression [odds ratio 0.56, 95% confidence interval (CI) 0.32, 0.99] and malnutrition (odds ratio 0.45, 95% CI 0.26, 0.78) by 12 months and improved concentration at Months 6 (0.23, 95% CI 0.04, 0.42) and 12 (0.46, 95% CI 0.22, 0.70). Participant empowerment augmented activity (4.67 MET/h, 95% CI 1.64, 7.69) and gait speed (0.06 m/s, 95% CI 0.00, 0.11) at 6 months, with sustained improvements in delayed recall (0.63, 95% CI 0.20, 1.06) and MoCA performance (1.29, 95% CI 0.54, 2.03), and less prevalent malnutrition (odds ratio 0.39, 95% CI 0.18, 0.84), 3 months after the intervention ceased.ConclusionsPragmatic multidomain intervention can diminish physical frailty, malnutrition, and depression and enhance cognitive performance among community- dwelling elders, especially - ¥75- year- olds; this might supplement healthy aging policies, probably more effectively if participants are empowered.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/156002/1/jcsm12534.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/156002/2/10.1002_jcsm.12534_Fig_S4.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/156002/3/jcsm12534_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/156002/4/10.1002_jcsm.12534_Fig_S2.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/156002/5/10.1002_jcsm.12534_Table_S3.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/156002/6/10.1002_jcsm.12534_Fig_S3.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/156002/7/10.1002_jcsm.12534_Appendix_S1.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/156002/8/10.1002_jcsm.12534_Table_S2.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/156002/9/10.1002_jcsm.12534_Table_S1.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/156002/10/10.1002_jcsm.12534_Fig_S1.pd

Epidemiology of acute otitis media among young children: A multiple database study in Taiwan

Background/PurposeAcute otitis media (AOM) is a common complication of upper respiratory tract infection (URTI) among children. The purpose of this study was to evaluate the epidemiology of AOM among young children in Taiwan, including the age incidence and seasonality by combining multiple databases.MethodsTwo country-based questionnaire survey studies had been conducted to evaluate the experience of otitis media (OM) among young children: one in 2007 and the other between 2005 and 2010. The number of OM cases (5% of population younger than 7 years) in 2005 and annual visiting rates for URTI from 2005 to 2010 obtained from the National Health Insurance Research Database of Taiwan were collected and comprised the third database. The fourth database comprised ambulatory visits of children with OM to a medical center in central Taiwan between 2005 and 2010.ResultsData from a total of 1099 questionnaires were entered into Database I in 2007, and data from 9705 questionnaires between 2005 and 2010 comprised Database II. There were 86,702 children (younger than 7 years, representing 5% of the whole population for this age group) retrieved from Database III in 2007, and 5,904 cases of OM in children between 2005 and 2010 in a hospital. In Database I, 7.46% children experienced at least one episode of AOM compared with 9.21% in Database II for children aged 5 years and younger. In Database III, 13.2% children younger than 7 years had AOM in 2005. The peak season of AOM among children was from March to May (Databases III and IV).ConclusionAOM was thought to be a very common disease among children; however, this comparative analysis showed that the overall prevalence of AOM among children younger than 5 years was only 20%, much lower than in other countries. AOM was more prevalent during the spring season, and still was similarly common after age 2 years

Association of combination antiretroviral therapy with risk of neurological diseases in patients with HIV/AIDS in Taiwan: a nested case-control study

Heterogeneous neurocognitive impairment remains an important issue, even in the era of combination antiretroviral therapy (cART), with an incidence ranging from 15% to 65%. Although ART drugs with higher penetration scores to the central nervous system (CNS) show better HIV replication control in the CNS, the association between CNS penetration effectiveness (CPE) scores and neurocognitive impairment remains inconclusive. To explore whether ART exposure is associated with the risk of neurological diseases among patients with HIV/AIDS, this study in Taiwan involved 2,571 patients with neurological diseases and 10,284 matched, randomly selected patients without neurological diseases between 2010 and 2017. A conditional logistic regression model was used in this study. The parameters for ART exposure included ART usage, timing of exposure, cumulative defined daily dose (DDD), adherence, and cumulative CPE score. Incident cases of neurological diseases, including CNS infections, cognitive disorders, vasculopathy, and peripheral neuropathy, were obtained from the National Health Insurance Research Database in Taiwan. Odds ratios (ORs) for the risk of neurological diseases were conducted using a multivariate conditional logistic regression model. Patients with a history of past exposure (OR: 1.68, 95% confidence interval [CI]:1.22–2.32), low cumulative DDDs (< 2,500) (OR: 1.28, 95% CI: 1.15–1.42), low adherence (0 < adherence (ADH) ≤ 0.8) (OR: 1.46, 95% CI: 1.30–1.64), or high cumulative CPE scores (>14) (OR: 1.34, 95% CI: 1.14–1.57) had a high risk of neurological diseases. When stratified by classes of ART drugs, patients with low cumulative DDDs or low adherence had a high risk of neurological diseases, including NRTIs, PIs, NNRTIs, INSTIs, and multi-drug tablets. Subgroup analyses also suggested that patients with low cumulative DDDs or low adherence had a high risk of neurological diseases when they had high cumulative CPE scores. Patients with high cumulative DDDs or medication adherence were protected against neurological diseases only when they had low cumulative CPE scores (≤ 14). Patients may be at risk for neurological diseases when they have low cumulative DDDs, low adherence, or usage with high cumulative CPE scores. Continuous usage and low cumulative CPE scores of ART drugs may benefit neurocognitive health in patients with HIV/AIDS

Polyenylpyrrole Derivatives Inhibit NLRP3 Inflammasome Activation and Inflammatory Mediator Expression by Reducing Reactive Oxygen Species Production and Mitogen-Activated Protein Kinase Activation

10.1371/journal.pone.0076754PLoS ONE810-POLN

IBMPFD disease-causing mutant VCP/p97 proteins are targets of autophagic-lysosomal degradation

The ubiquitin-proteasome system (UPS) degrades soluble proteins and small aggregates, whereas macroautophagy (autophagy herein) eliminates larger protein aggregates, tangles and even whole organelles in a lysosome-dependent manner. VCP/p97 was implicated in both pathways. VCP/p97 mutations cause a rare multisystem disease called IBMPFD (Inclusion Body Myopathy with Paget's Disease and Frontotemporal Dementia). Here, we studied the role IBMPFD-related mutants of VCP/p97 in autophagy. In contrast with the wild-type VCP/p97 protein or R155C or R191Q mutants, the P137L mutant was aggregate-prone. We showed that, unlike commonly studied R155C or R191Q mutants, the P137L mutant protein stimulated both autophagosome and autolysosome formation. Moreover, P137L mutant protein itself was a substrate of autophagy. Starvation- and mTOR inhibition-induced autophagy led to the degradation of the P137L mutant protein, while preserving the wild-type and functional VCP/p97. Strikingly, similar to the P137L mutant, other IBMPFD-related VCP/p97 mutants, namely R93C and G157R mutants induced autophagosome and autolysosome formation; and G157R mutant formed aggregates that could be cleared by autophagy. Therefore, cellular phenotypes caused by P137L mutant expression were not isolated observations, and some other IBMPFD disease-related VCP/p97 mutations could lead to similar outcomes. Our results indicate that cellular mechanisms leading to IBMPFD disease may be various, and underline the importance of studying different disease-associated mutations in order to better understand human pathologies and tailor mutation-specific treatment strategies

Gene-educational attainment interactions in a multi-population genome-wide meta-analysis identify novel lipid loci

Introduction: Educational attainment, widely used in epidemiologic studies as a surrogate for socioeconomic status, is a predictor of cardiovascular health outcomes. Methods: A two-stage genome-wide meta-analysis of low-density lipoprotein cholesterol (LDL), high-density lipoprotein cholesterol (HDL), and triglyceride (TG) levels was performed while accounting for gene-educational attainment interactions in up to 226,315 individuals from five population groups. We considered two educational attainment variables: “Some College” (yes/no, for any education beyond high school) and “Graduated College” (yes/no, for completing a 4-year college degree). Genome-wide significant (p &lt; 5 × 10−8) and suggestive (p &lt; 1 × 10−6) variants were identified in Stage 1 (in up to 108,784 individuals) through genome-wide analysis, and those variants were followed up in Stage 2 studies (in up to 117,531 individuals). Results: In combined analysis of Stages 1 and 2, we identified 18 novel lipid loci (nine for LDL, seven for HDL, and two for TG) by two degree-of-freedom (2 DF) joint tests of main and interaction effects. Four loci showed significant interaction with educational attainment. Two loci were significant only in cross-population analyses. Several loci include genes with known or suggested roles in adipose (FOXP1, MBOAT4, SKP2, STIM1, STX4), brain (BRI3, FILIP1, FOXP1, LINC00290, LMTK2, MBOAT4, MYO6, SENP6, SRGAP3, STIM1, TMEM167A, TMEM30A), and liver (BRI3, FOXP1) biology, highlighting the potential importance of brain-adipose-liver communication in the regulation of lipid metabolism. An investigation of the potential druggability of genes in identified loci resulted in five gene targets shown to interact with drugs approved by the Food and Drug Administration, including genes with roles in adipose and brain tissue. Discussion: Genome-wide interaction analysis of educational attainment identified novel lipid loci not previously detected by analyses limited to main genetic effects.</p