Excited state intramolecular proton transfer in hydroxyanthraquinones: Toward predicting fading of organic red colorants in art.

Compositionally similar organic red colorants in the anthraquinone family, whose photodegradation can cause irreversible color and stability changes, have long been used in works of art. Different organic reds, and their multiple chromophores, suffer degradation disparately. Understanding the details of these molecules' degradation therefore provides a window into their behavior in works of art and may assist the development of improved conservation methods. According to one proposed model of photodegradation dynamics, intramolecular proton transfer provides a kinetically favored decay pathway in some photoexcited chromophores, preventing degradation-promoting electron transfer (ET). To further test this model, we measured excited state lifetimes of substituted gas-phase anthraquinones using high-level theory to explain the experimental results. The data show a general structural trend: Anthraquinones with 1,4-OH substitution are long-lived and prone to damaging ET, while excited state intramolecular proton transfers promote efficient quenching for hydroxyanthraquinones that lack this motif

Diabetes causes marked inhibition of mitochondrial metabolism in pancreatic β-cells

Diabetes is a global health problem caused primarily by the inability of pancreatic β-cells to secrete adequate levels of insulin. The molecular mechanisms underlying the progressive failure of β-cells to respond to glucose in type-2 diabetes remain unresolved. Using a combination of transcriptomics and proteomics, we find significant dysregulation of major metabolic pathways in islets of diabetic βV59M mice, a non-obese, eulipidaemic diabetes model. Multiple genes/proteins involved in glycolysis/gluconeogenesis are upregulated, whereas those involved in oxidative phosphorylation are downregulated. In isolated islets, glucose-induced increases in NADH and ATP are impaired and both oxidative and glycolytic glucose metabolism are reduced. INS-1 β-cells cultured chronically at high glucose show similar changes in protein expression and reduced glucose-stimulated oxygen consumption: targeted metabolomics reveals impaired metabolism. These data indicate hyperglycaemia induces metabolic changes in β-cells that markedly reduce mitochondrial metabolism and ATP synthesis. We propose this underlies the progressive failure of β-cells in diabetes.Peer reviewe

Coronary artery bypass grafting and sensorineural hearing loss, a cohort study

BACKGROUND: Sudden sensorineural hearing loss is routinely encountered by the otologist. The etiology is varied and often identifiable. One of the relatively less frequent causes is surgery. Apart from being an established entity with otological surgeries, sensorineural hearing loss has also been known to occur after non-otological procedures under general anesthesia. Commonest amongst these procedures is cardiopulmonary bypass, an association that has long been recognized. However, despite the proposition of diverse hypotheses in the past, the pathophysiology remains unclear. METHODS: The study is a prospective matched cohort study that will be carried out in Aga Khan University Hospital, Karachi, Pakistan. Participants among exposed would include all those patients who would be undergoing coronary artery bypass surgery in the hospital who fall under the criteria for inclusion. Unexposed group would comprise of patients undergoing a non-bypass procedure of similar duration under the same type of anesthesia who meet the selection criteria. Both these groups will undergo audiometric testing at our hospital on three different occasions during the course of this study. Initially before the procedure to test the baseline hearing capacity; then one week after the procedure to assess any changes in hearing ability following the surgery; and finally a third audiogram at six weeks follow-up to assess further changes in any hearing deficits noted during the second phase of testing. Certain variables including the subjects' demographics and those concerning the procedure itself will be noted and used later for risk factors analysis. A detailed past medical and surgical history will also be obtained. Data analysis would include calculation of relative risk and significance of the results, by running the chi-square test. Other statistical tests like Fisher exact test may then be employed to facilitate data interpretation. Continuous scale may then be employed and multivariate linear regression used. DISCUSSION: This study is planned to obtain a better understanding of the correlation between sudden sensorineural hearing loss and cardiopulmonary bypass. Being the first major cohort trial in this line of investigation, the project is designed to identify the existence of any significant relationship between cardiopulmonary bypass and sensorineural hearing deficit

Murine model for Fusarium oxysporum invasive fusariosis reveals organ-specific structures for dissemination and long-term persistence

Peer reviewedPublisher PD

Novel insights into host-fungal pathogen interactions derived from live-cell imaging

Acknowledgments The authors acknowledge funding from the Wellcome Trust (080088, 086827, 075470 and 099215) including a Wellcome Trust Strategic Award for Medical Mycology and Fungal Immunology 097377 and FP7-2007–2013 grant agreement HEALTH-F2-2010-260338–ALLFUN to NARG.Peer reviewedPublisher PD

A systematic review and meta-synthesis of the impact of low back pain on people's lives

Copyright @ 2014 Froud et al.; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited.Background - Low back pain (LBP) is a common and costly problem that many interpret within a biopsychosocial model. There is renewed concern that core-sets of outcome measures do not capture what is important. To inform debate about the coverage of back pain outcome measure core-sets, and to suggest areas worthy of exploration within healthcare consultations, we have synthesised the qualitative literature on the impact of low back pain on people’s lives. Methods - Two reviewers searched CINAHL, Embase, PsycINFO, PEDro, and Medline, identifying qualitative studies of people’s experiences of non-specific LBP. Abstracted data were thematic coded and synthesised using a meta-ethnographic, and a meta-narrative approach. Results - We included 49 papers describing 42 studies. Patients are concerned with engagement in meaningful activities; but they also want to be believed and have their experiences and identity, as someone ‘doing battle’ with pain, validated. Patients seek diagnosis, treatment, and cure, but also reassurance of the absence of pathology. Some struggle to meet social expectations and obligations. When these are achieved, the credibility of their pain/disability claims can be jeopardised. Others withdraw, fearful of disapproval, or unable or unwilling to accommodate social demands. Patients generally seek to regain their pre-pain levels of health, and physical and emotional stability. After time, this can be perceived to become unrealistic and some adjust their expectations accordingly. Conclusions - The social component of the biopsychosocial model is not well represented in current core-sets of outcome measures. Clinicians should appreciate that the broader impact of low back pain includes social factors; this may be crucial to improving patients’ experiences of health care. Researchers should consider social factors to help develop a portfolio of more relevant outcome measures.Arthritis Research U

Feasibility and results of a randomised pilot-study of pre-discharge occupational therapy home visits

BACKGROUND: Pre-discharge home visits aim to maximise independence in the community. These visits involve assessment of a person in their own home prior to discharge from hospital, typically by an occupational therapist. The therapist may provide equipment, adapt the home environment and/or provide education. The aims of this study were to investigate the feasibility of a randomised controlled trial in a clinical setting and the effect of pre-discharge home visits on functional performance in older people undergoing rehabilitation. METHODS: Ten patients participating in an inpatient rehabilitation program were randomly assigned to receive either a pre-discharge home visit (intervention), or standard practice in-hospital assessment and education (control), both conducted by an occupational therapist. The pre-discharge home visit involved assessment of the older person's function and environment, and education, and took an average of 1.5 hours. The hospital-based interview took an average of 40 minutes. Outcome data were collected by a blinded assessor at 0, 2, 4, 8 and 12 weeks. Outcomes included performance of activities of daily living, reintegration to community living, quality of life, readmission and fall rates. RESULTS: Recruitment of 10 participants was slow and took three months. Observed performance of functional abilities did not differ between groups due to the small sample size. Difference in activities of daily living participation, as recorded by the Nottingham Extended Activities of Daily Living scale, was statistically significant but wide confidence intervals and low statistical power limit interpretation of results. CONCLUSION: Evaluation of pre-discharge home visits by occupational therapists in a rehabilitation setting is feasible, but a more effective recruitment strategy for a main study is favored by application of a multi-centre setting

CNS Recruitment of CD8+ T Lymphocytes Specific for a Peripheral Virus Infection Triggers Neuropathogenesis during Polymicrobial Challenge

Although viruses have been implicated in central nervous system (CNS) diseases of unknown etiology, including multiple sclerosis and amyotrophic lateral sclerosis, the reproducible identification of viral triggers in such diseases has been largely unsuccessful. Here, we explore the hypothesis that viruses need not replicate in the tissue in which they cause disease; specifically, that a peripheral infection might trigger CNS pathology. To test this idea, we utilized a transgenic mouse model in which we found that immune cells responding to a peripheral infection are recruited to the CNS, where they trigger neurological damage. In this model, mice are infected with both CNS-restricted measles virus (MV) and peripherally restricted lymphocytic choriomeningitis virus (LCMV). While infection with either virus alone resulted in no illness, infection with both viruses caused disease in all mice, with ∼50% dying following seizures. Co-infection resulted in a 12-fold increase in the number of CD8+ T cells in the brain as compared to MV infection alone. Tetramer analysis revealed that a substantial proportion (>35%) of these infiltrating CD8+ lymphocytes were LCMV-specific, despite no detectable LCMV in CNS tissues. Mechanistically, CNS disease was due to edema, induced in a CD8-dependent but perforin-independent manner, and brain herniation, similar to that observed in mice challenged intracerebrally with LCMV. These results indicate that T cell trafficking can be influenced by other ongoing immune challenges, and that CD8+ T cell recruitment to the brain can trigger CNS disease in the apparent absence of cognate antigen. By extrapolation, human CNS diseases of unknown etiology need not be associated with infection with any particular agent; rather, a condition that compromises and activates the blood-brain barrier and adjacent brain parenchyma can render the CNS susceptible to pathogen-independent immune attack

Overview of the VA Quality Enhancement Research Initiative (QUERI) and QUERI theme articles: QUERI Series

<p>Abstract</p> <p>Background</p> <p>Continuing challenges to timely adoption of evidence-based clinical practices in healthcare have generated intense interest in the development and application of new implementation methods and frameworks. These challenges led the United States (U.S.) Department of Veterans Affairs (VA) to create the Quality Enhancement Research Initiative (QUERI) in the late 1990s. QUERI's purpose was to harness VA's health services research expertise and resources in an ongoing system-wide effort to improve the performance of the VA healthcare system and, thus, quality of care for veterans. QUERI in turn created a systematic means of involving VA researchers both in enhancing VA healthcare quality, by implementing evidence-based practices, and in contributing to the continuing development of implementation science.</p> <p>The efforts of VA researchers to improve healthcare delivery practices through QUERI and related initiatives are documented in a growing body of literature. The scientific frameworks and methodological approaches developed and employed by QUERI are less well described. A QUERI Series of articles in <it>Implementation Science </it>will illustrate many of these QUERI tools. This <it>Overview </it>article introduces both QUERI and the Series.</p> <p>Methods</p> <p>The <it>Overview </it>briefly explains the purpose and context of the QUERI Program. It then describes the following: the key operational structure of QUERI Centers, guiding frameworks designed to enhance implementation and related research, QUERI's progress and promise to date, and the Series' general content. QUERI's frameworks include a core set of steps for diagnosing and closing quality gaps and, simultaneously, advancing implementation science. Throughout the paper, the envisioned involvement and activities of VA researchers within QUERI Centers also are highlighted. The Series is then described, illustrating the use of QUERI frameworks and other tools designed to respond to implementation challenges.</p> <p>Conclusion</p> <p>QUERI's simultaneous pursuit of improvement and research goals within a large healthcare system may be unique. However, descriptions of this still-evolving effort, including its conceptual frameworks, methodological approaches, and enabling processes, should have applicability to implementation researchers in a range of health care settings. Thus, the <it>Series </it>is offered as a resource for other implementation research programs and researchers pursuing common goals in improving care and developing the field of implementation science.</p