A non-cardiomyocyte autonomous mechanism of cardioprotection involving the SLO1 BK channel

Opening of BK-type Ca2+ activated K+ channels protects the heart against ischemia-reperfusion (IR) injury. However, the location of BK channels responsible for cardioprotection is debated. Herein we confirmed that openers of the SLO1 BK channel, NS1619 and NS11021, were protective in a mouse perfused heart model of IR injury. As anticipated, deletion of the Slo1 gene blocked this protection. However, in an isolated cardiomyocyte model of IR injury, protection by NS1619 and NS11021 was insensitive to Slo1 deletion. These data suggest that protection in intact hearts occurs by a non-cardiomyocyte autonomous, SLO1-dependent, mechanism. In this regard, an in-situ assay of intrinsic cardiac neuronal function (tachycardic response to nicotine) revealed that NS1619 preserved cardiac neurons following IR injury. Furthermore, blockade of synaptic transmission by hexamethonium suppressed cardioprotection by NS1619 in intact hearts. These results suggest that opening SLO1 protects the heart during IR injury, via a mechanism that involves intrinsic cardiac neurons. Cardiac neuronal ion channels may be useful therapeutic targets for eliciting cardioprotection

Aptamer-based multiplexed proteomic technology for biomarker discovery

Interrogation of the human proteome in a highly multiplexed and efficient manner remains a coveted and challenging goal in biology. We present a new aptamer-based proteomic technology for biomarker discovery capable of simultaneously measuring thousands of proteins from small sample volumes (15 [mu]L of serum or plasma). Our current assay allows us to measure ~800 proteins with very low limits of detection (1 pM average), 7 logs of overall dynamic range, and 5% average coefficient of variation. This technology is enabled by a new generation of aptamers that contain chemically modified nucleotides, which greatly expand the physicochemical diversity of the large randomized nucleic acid libraries from which the aptamers are selected. Proteins in complex matrices such as plasma are measured with a process that transforms a signature of protein concentrations into a corresponding DNA aptamer concentration signature, which is then quantified with a DNA microarray. In essence, our assay takes advantage of the dual nature of aptamers as both folded binding entities with defined shapes and unique sequences recognizable by specific hybridization probes. To demonstrate the utility of our proteomics biomarker discovery technology, we applied it to a clinical study of chronic kidney disease (CKD). We identified two well known CKD biomarkers as well as an additional 58 potential CKD biomarkers. These results demonstrate the potential utility of our technology to discover unique protein signatures characteristic of various disease states. More generally, we describe a versatile and powerful tool that allows large-scale comparison of proteome profiles among discrete populations. This unbiased and highly multiplexed search engine will enable the discovery of novel biomarkers in a manner that is unencumbered by our incomplete knowledge of biology, thereby helping to advance the next generation of evidence-based medicine

Risk Adjustment Measures and Outcome Measures for Prehospital Trauma Research: Recommendations from the Emergency Medical Services Outcomes Project (EMSOP)

Objectives:  The objectives were to conduct a comprehensive, systematic review of the literature for risk adjustment measures (RAMs) and outcome measures (OMs) for prehospital trauma research and to use a structured expert panel process to recommend measures for use in future emergency medical services (EMS) trauma outcomes research. Methods:  A systematic literature search and review was performed identifying the published studies evaluating RAMs and OMs for prehospital injury research. An explicit structured review of all articles pertaining to each measure was conducted using the previously established methodology developed by the Canadian Physiotherapy Association (“Physical Rehabilitation Outcome Measures”). Results:  Among the 4,885 articles reviewed, 96 RAMs and/or OMs were identified from the existing literature (January 1958 to February 2010). Only one measure, the Glasgow Coma Scale (GCS), currently meets Level 1 quality of evidence status and a Category 1 (strong) recommendation for use in EMS trauma research. Twelve RAMs or OMs received Category 2 status (promising, but not sufficient current evidence to strongly recommend), including the motor component of GCS, simplified motor score (SMS), the simplified verbal score (SVS), the revised trauma score (RTS), the prehospital index (PHI), EMS provider judgment, the revised trauma index (RTI), the rapid acute physiology score (RAPS), the rapid emergency medicine score (REMS), the field trauma triage (FTT), the pediatric triage rule, and the out‐of‐hospital decision rule for pediatrics. Conclusions:  Using a previously published process, a structured literature review, and consensus expert panel opinion, only the GCS can currently be firmly recommended as a specific RAM or OM for prehospital trauma research (along with core measures that have already been established and published). This effort highlights the paucity of reliable, validated RAMs and OMs currently available for outcomes research in the prehospital setting and hopefully will encourage additional, methodologically sound evaluations of the promising, Category 2 RAMs and OMs, as well as the development of new measures.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/87101/1/j.1553-2712.2011.01148.x.pd

Evidence for link between modelled trends in Antarctic sea ice and underestimated westerly wind changes

Despite global warming, total Antarctic sea ice coverage increased over 1979-2013. However, the majority of Coupled Model Intercomparison Project phase 5 models simulate a decline. Mechanisms causing this discrepancy have so far remained elusive. Here we show that weaker trends in the intensification of the Southern Hemisphere westerly wind jet simulated by the models may contribute to this disparity. During austral summer, a strengthened jet leads to increased upwelling of cooler subsurface water and strengthened equatorward transport, conducive to increased sea ice. As the majority of models underestimate summer jet trends, this cooling process is underestimated compared with observations and is insufficient to offset warming in the models. Through the sea ice-albedo feedback, models produce a high-latitude surface ocean warming and sea ice decline, contrasting the observed net cooling and sea ice increase. A realistic simulation of observed wind changes may be crucial for reproducing the recent observed sea ice increase

Teaching Music : The Urban Experience

https://digitalcommons.montclair.edu/all_books/1385/thumbnail.jp

Critical Care Nursing of the Elderly, 2nd Edition

Meredith Wallace [Kazer] (with E. Flaherty) is a contributing author, Assessment and Management in Pain . Book description: This volume, like the first edition, is an important milestone in the field of gerontological nursing, reflecting the growing number of nurses actively involved in geriatric care and clinical research in hospitals. Thoroughly revised and updated, the second edition provides the collective thinking of experts who strive to ask and answer such key questions as: Who should receive advanced technological care? When should care stop? and Who determines vitality? The comprehensive coverage includes sound guidelines for nursing assessment and management; basic clinical issues with elderly populations; specialized practice protocols and advances; and lively discussion of social and policy issues.https://digitalcommons.fairfield.edu/nursing-books/1066/thumbnail.jp

Loneliness in Older Adults Living with HIV

We conducted a cross-sectional study among HIV-positive adults age ≥ 50 in San Francisco to evaluate the frequency of loneliness, characteristics of those who reported loneliness, and the association of loneliness with functional impairment and health-related quality of life (HRQoL). Participants (N = 356) were predominately male (85%); 57% were white; median age was 56. 58% reported any loneliness symptoms with 24% reporting mild, 22% moderate and 12% severe loneliness. Lonely participants were more likely to report depression, alcohol and tobacco use, and have fewer relationships. In unadjusted models, loneliness was associated with functional impairment and poor HRQoL. In adjusted models, low income and depression remained associated with poor HRQoL, while low income, higher VACS index and depression were associated with functional impairment. A comprehensive care approach, incorporating mental health and psychosocial assessments with more traditional clinical assessments, will be needed to improve health outcomes for the aging HIV-positive population

Geriatric Assessments and Association With VACS Index Among HIV-Infected Older Adults in San Francisco

ObjectivesTo perform geriatric assessments in older HIV-infected adults in San Francisco and examine the association with age and the Veterans Aging Cohort Study (VACS) index scores.MethodsA cross-sectional study was conducted from 2012 to 2014 among HIV-infected patients ≥50 years at 2 San Francisco-based HIV clinics. We evaluated 4 health domains: (1) physical health and function (activities of daily living), instrumental activities of daily living (IADL), falls, gait speed, (2) social support (physical and perceived support, loneliness), (3) mental health (depression, anxiety, posttraumatic stress disorder) and cognition, and (4) behavioral and general health (antiretroviral adherence and quality of life). Contingency table and rank-sum analyses examined associations between these domains with age and VACS index scores.ResultsThree hundred fifty-nine patients completed assessments (median age 57; 85% male; 57% white; 72% >high school education). On functional assessment, 39% reported dependence with ≥1 IADL, and 40% reported falls in the previous year. Fifty-eight percent experienced loneliness, 60% the lowest levels of perceived social support, 55% depression, and 12% posttraumatic stress disorder. Forty percent had possible mild cognitive impairment. Thirty percent reported poor or fair quality of life. Older age was associated with lower CD4 counts, balance problems, slower gait, lower anxiety, poorer general health, and higher antiretroviral adherence. VACS Index score was associated with dependence in ≥1 IADL and antiretroviral adherence.ConclusionIn a large sample of older HIV-infected adults, multiple significant aging-related conditions were identified. Integrating geriatric assessment tools into HIV/AIDS clinical care may help target interventions to optimize clinical care and quality of life for older HIV-infected individuals