Electrochemistry of ubiquinones Menaquinones and plastoquinones in aprotic solvents

AbstractFirst and second half-wave reduction potentials of a series of 1,4-benzo- and 1,4-naphtho-quinones related to the naturally occurring ubiquinones, plastoquinones and menaquinones are correlated with substituent effects. Notably, E12 of 2,3-dimethoxy-1,4-benzoquinone is positive of the values for the 2,5- and 2,6-dimethoxy isomers, and of the value for methoxy-1,4-benzoquinone. This phenomenon is attributed to steric inhibition of resonance when two methoxy groups occupy adjacent positions, and the significance of this orientation in the ubiquinone series is highlighted

A journey without maps—Understanding the costs of caring for dependent older people in Nigeria, China, Mexico and Peru

Purpose of the study: Populations in Latin America, Asia and sub-Saharan Africa are rapidly ageing. The extent to which traditional systems of family support and security can manage the care of increased numbers of older people with chronic health problems is unclear. Our aim was to explore the social and economic effects of caring for an older dependent person, including insight into pathways to economic vulnerability. Design & methods: We carried out a series of household case studies across urban and rural sites in Peru, Mexico, China and Nigeria (n = 24), as part of a cross-sectional study, nested within the 10/66 Dementia Research Group cohort. Case studies consisted of in-depth narrative style interviews (n = 60) with multiple family members, including the older dependent person. Results: Governments were largely uninvolved in the care and support of older dependent people, leaving families to negotiate a ‘journey without maps’. Women were de facto caregivers but the traditional role of female relative as caregiver was beginning to be contested. Household composition was flexible and responsive to changing needs of multiple generations but family finances were stretched. Implications: Governments are lagging behind sociodemographic and social change. There is an urgent need for policy frameworks to support and supplement inputs from families. These should include community-based and residential care services, disability benefits and carers allowances. Further enhancement of health insurance schemes and scale-up of social pensions are an important component of bolstering the security of dependent older people and supporting their continued social and economic participation

Flavin-Catalyzed Insertion of Oxygen into Rhenium-Methyl Bonds

Article discussing flavin-catalyzed insertion of oxygen into rhenium-methyl bonds

DeLLITE Depression in late life: an intervention trial of exercise. Design and recruitment of a randomised controlled trial

<p>Abstract</p> <p>Background</p> <p>Physical activity shows potential in combating the poor outcomes associated with depression in older people. Meta-analyses show gaps in the research with poor trial design compromising certainty in conclusions and few programmes showing sustained effects.</p> <p>Methods/design</p> <p>The Depression in Late Life: an Intervention Trial of Exercise (DeLLITE) is a 12 month randomised controlled trial of a physical activity intervention to increase functional status in people aged 75 years and older with depressive symptoms. The intervention involves an individualised activity programme based on goal setting and progression of difficulty of activities delivered by a trained nurse during 8 home visits over 6 months. The control group received time matched home visits to discuss social contacts and networks. Baseline, 6 and 12 months measures were assessed in face to face visits with the primary outcome being functional status (SPPB, NEADL). Secondary outcomes include depressive symptoms (Geriatric Depression Scale), quality of life (SF-36), physical activity (AHS Physical Activity Questionnaire) and falls (self report).</p> <p>Discussion</p> <p>Due to report in 2008 the DeLLITE study has recruited 70% of those eligible and tests the efficacy of a home based, goal setting physical activity programme in improving function, mood and quality of life in older people with depressive symptomatology. If successful in improving function and mood this trial could prove for the first time that there are long term health benefit of physical activity, independent of social activity, in this high risk group who consume excess health related costs.</p> <p>Trial registration</p> <p>Australian and New Zealand Clinical Trials Register ACTRN12605000475640</p

Induction of multi-functional T cells in a phase I clinical trial of dendritic cell immunotherapy in Hepatitis C virus infected individuals

We have previously reported a world-first phase I clinical trial to treat HCV patients using monocyte-derived dendritic cells (Mo-DC) loaded with HCV-specific lipopeptides. While the brief treatment proved to be safe, it failed to reduce the viral load and induced only transient cell-mediated immune responses, measured by IFNc ELIspot. Here we reanalysed the PBMC samples from this trial to further elucidate the immunological events associated with the Mo-DC therapy. We found that HCV-specific single- and multi-cytokine secreting T cells were induced by the Mo-DC immunotherapy in some patients, although at irregular intervals and not consistently directed to the same HCV antigen. Despite the vaccination, the responses were generally poor in quality and comprised of primarily single-cytokine secreting cells. The frequency of FOXP3+ regulatory T cells (Treg) fluctuated following DC infusion and eventually dropped to below baseline by week 12, an interesting trend suggesting that the vaccination may have resulted in a more subtle outcome than was initially apparent. Our data suggested that Mo-DC therapy induced complex immune responses in vivo that may or may not lead to clinical benefit.Shuo Li, Stuart Roberts, Magdalena Plebanski, Maelenn Gouillou, Tim Spelman, Philippe Latour, David Jackson, Lorena Brown, Rosemary L. Sparrow, H. Miles Prince, Derek Hart, Bruce E. Loveland and Eric J. Gowan

Future research directions in pneumonia

Copyright © 2018 by the American Thoracic Society. Pneumonia is a complex pulmonary disease in need of new clinical approaches. Although triggered by a pathogen, pneumonia often results from dysregulations of host defense that likely precede infection. The coordinated activities of immune resistance and tissue resilience then dictate whether and how pneumonia progresses or resolves. Inadequate or inappropriate host responses lead to more severe outcomes such as acute respiratory distress syndrome and to organ dysfunction beyond the lungs and over extended time frames after pathogen clearance, some of which increase the risk for subsequent pneumonia. Improved understanding of such host responses will guide the development of novel approaches for preventing and curing pneumonia and for mitigating the subsequent pulmonary and extrapulmonary complications of pneumonia. The NHLBI assembled a working group of extramural investigators to prioritize avenues of host-directed pneumonia research that should yield novel approaches for interrupting the cycle of unhealthy decline caused by pneumonia. This report summarizes the working group’s specific recommendations in the areas of pneumonia susceptibility, host response, and consequences. Overarching goals include the development of more host-focused clinical approaches for preventing and treating pneumonia, the generation of predictive tools (for pneumonia occurrence, severity, and outcome), and the elucidation of mechanisms mediating immune resistance and tissue resilience in the lung. Specific areas of research are highlighted as especially promising for making advances against pneumonia

Re-visiting Meltsner: Policy Advice Systems and the Multi-Dimensional Nature of Professional Policy Analysis

10.2139/ssrn.15462511-2

Acute Flaccid Paralysis and West Nile Virus Infection

Acute weakness associated with West Nile virus (WNV) infection has previously been attributed to a peripheral demyelinating process (Guillain-Barré syndrome); however, the exact etiology of this acute flaccid paralysis has not been systematically assessed. To thoroughly describe the clinical, laboratory, and electrodiagnostic features of this paralysis syndrome, we evaluated acute flaccid paralysis that developed in seven patients in the setting of acute WNV infection, consecutively identified in four hospitals in St. Tammany Parish and New Orleans, Louisiana, and Jackson, Mississippi. All patients had acute onset of asymmetric weakness and areflexia but no sensory abnormalities. Clinical and electrodiagnostic data suggested the involvement of spinal anterior horn cells, resulting in a poliomyelitis-like syndrome. In areas in which transmission is occurring, WNV infection should be considered in patients with acute flaccid paralysis. Recognition that such weakness may be of spinal origin may prevent inappropriate treatment and diagnostic testing

Pan-Cancer Analysis of lncRNA Regulation Supports Their Targeting of Cancer Genes in Each Tumor Context

Long noncoding RNAs (lncRNAs) are commonly dys-regulated in tumors, but only a handful are known toplay pathophysiological roles in cancer. We inferredlncRNAs that dysregulate cancer pathways, onco-genes, and tumor suppressors (cancer genes) bymodeling their effects on the activity of transcriptionfactors, RNA-binding proteins, and microRNAs in5,185 TCGA tumors and 1,019 ENCODE assays.Our predictions included hundreds of candidateonco- and tumor-suppressor lncRNAs (cancerlncRNAs) whose somatic alterations account for thedysregulation of dozens of cancer genes and path-ways in each of 14 tumor contexts. To demonstrateproof of concept, we showed that perturbations tar-geting OIP5-AS1 (an inferred tumor suppressor) andTUG1 and WT1-AS (inferred onco-lncRNAs) dysre-gulated cancer genes and altered proliferation ofbreast and gynecologic cancer cells. Our analysis in-dicates that, although most lncRNAs are dysregu-lated in a tumor-specific manner, some, includingOIP5-AS1, TUG1, NEAT1, MEG3, and TSIX, synergis-tically dysregulate cancer pathways in multiple tumorcontexts

Genomic, Pathway Network, and Immunologic Features Distinguishing Squamous Carcinomas

This integrated, multiplatform PanCancer Atlas study co-mapped and identified distinguishing molecular features of squamous cell carcinomas (SCCs) from five sites associated with smokin