Dynamic Change of Awareness during Meditation Techniques: Neural and Physiological Correlates

Recent fndings illustrate how changes in consciousness accommodated by neural correlates and plasticity of the brain advance a model of perceptual change as a function of meditative practice. During the mindbody response neural correlates of changing awareness illustrate how the autonomic nervous system shifts from a sympathetic dominant to a parasympathetic dominant state. Expansion of awareness during the practice of meditation techniques can be linked to the Default Mode Network (DMN), a network of brain regions that is active when the one is not focused on the outside world and the brain is restful yet awake (Chen et al., 2008). A model is presented illustrating the dynamic mindbody response before and after mindfulness meditation, and connections are made with prefrontal cortex activity, the cardiac and respiratory center, the thalamus and amygdala, the DMN and cortical function connectivity. The default status of the DMN changes corresponding to autonomic modulation resulting from meditation practice

Interferon-α regulates glutaminase 1 promoter through STAT1 phosphorylation: relevance to HIV-1 associated neurocognitive disorders.

HIV-1 associated neurocognitive disorders (HAND) develop during progressive HIV-1 infection and affect up to 50% of infected individuals. Activated microglia and macrophages are critical cell populations that are involved in the pathogenesis of HAND, which is specifically related to the production and release of various soluble neurotoxic factors including glutamate. In the central nervous system (CNS), glutamate is typically derived from glutamine by mitochondrial enzyme glutaminase. Our previous study has shown that glutaminase is upregulated in HIV-1 infected monocyte-derived-macrophages (MDM) and microglia. However, how HIV-1 leads to glutaminase upregulation, or how glutaminase expression is regulated in general, remains unclear. In this study, using a dual-luciferase reporter assay system, we demonstrated that interferon (IFN) α specifically activated the glutaminase 1 (GLS1) promoter. Furthermore, IFN-α treatment increased signal transducer and activator of transcription 1 (STAT1) phosphorylation and glutaminase mRNA and protein levels. IFN-α stimulation of GLS1 promoter activity correlated to STAT1 phosphorylation and was reduced by fludarabine, a chemical that inhibits STAT1 phosphorylation. Interestingly, STAT1 was found to directly bind to the GLS1 promoter in MDM, an effect that was dependent on STAT1 phosphorylation and significantly enhanced by IFN-α treatment. More importantly, HIV-1 infection increased STAT1 phosphorylation and STAT1 binding to the GLS1 promoter, which was associated with increased glutamate levels. The clinical relevance of these findings was further corroborated with investigation of post-mortem brain tissues. The glutaminase C (GAC, one isoform of GLS1) mRNA levels in HIV associated-dementia (HAD) individuals correlate with STAT1 (

ISCEV extended protocol for VEP methods of estimation of visual acuity

The International Society for Clinical Electrophysiology of Vision (ISCEV) standard for visual evoked potentials (VEPs) describes a minimum procedure for clinical VEP testing and encourages more extensive testing. This ISCEV extended protocol is an extension to the VEP standard. It describes procedures for recording multiple VEPs to a range of sizes of pattern stimuli to establish the VEP spatial frequency limit (threshold) and for relating this limit to visual acuity

VEP estimation of visual acuity: a systematic review

PURPOSE:Visual evoked potentials (VEPs) can be used to measure visual resolution via a spatial frequency (SF) limit as an objective estimate of visual acuity. The aim of this systematic review is to collate descriptions of the VEP SF limit in humans, healthy and disordered, and to assess how accurately and precisely VEP SF limits reflect visual acuity. METHODS:The protocol methodology followed the PRISMA statement. Multiple databases were searched using "VEP" and "acuity" and associated terms, plus hand search: titles, abstracts or full text were reviewed for eligibility. Data extracted included VEP SF limits, stimulus protocols, VEP recording and analysis techniques and correspondence with behavioural acuity for normally sighted healthy adults, typically developing infants and children, healthy adults with artificially degraded vision and patients with ophthalmic or neurological conditions. RESULTS:A total of 155 studies are included. Commonly used stimulus, recording and analysis techniques are summarised. Average healthy adult VEP SF limits vary from 15 to 40 cpd, depend on stimulus, recording and analysis techniques and are often, but not always, poorer than behavioural acuity measured either psychophysically with an identical stimulus or with a clinical acuity test. The difference between VEP SF limit and behavioural acuity is variable and strongly dependent on the VEP stimulus and choice of acuity test. VEP SF limits mature rapidly, from 1.5 to 9 cpd by the end of the first month of life to 12-20 cpd by 8-12 months, with slower improvement to 20-40 cpd by 3-5 years. VEP SF limits are much better than behavioural thresholds in the youngest, typically developing infants. This difference lessens with age and reaches equivalence between 1 and 2 years; from around 3-5 years, behavioural acuity is better than the VEP SF limit, as for adults. Healthy, artificially blurred adults had slightly better behavioural acuity than VEP SF limits across a wide range of acuities, while adults with heterogeneous ophthalmic or neurological pathologies causing reduced acuity showed a much wider and less consistent relationship. For refractive error, ocular media opacity or pathology primarily affecting the retina, VEP SF limits and behavioural acuity had a fairly consistent relationship across a wide range of acuity. This relationship was much less consistent or close for primarily macular, optic nerve or neurological conditions such as amblyopia. VEP SF limits were almost always normal in patients with non-organic visual acuity loss. CONCLUSIONS:The VEP SF limit has great utility as an objective acuity estimator, especially in pre-verbal children or patients of any age with motor or learning impairments which prevent reliable measurement of behavioural acuity. Its diagnostic power depends heavily on adequate, age-stratified, reference data, age-stratified empirical calibration with behavioural acuity, and interpretation in the light of other electrophysiological and clinical findings. Future developments could encompass faster, more objective and robust techniques such as real-time, adaptive control. REGISTRATION:International prospective register of systematic reviews PROSPERO (https://www.crd.york.ac.uk/PROSPERO/), registration number CRD42018085666

ISCEV guidelines for calibration and verification of stimuli and recording instruments (2023 update)

This document developed by the International Society for Clinical Electrophysiology of Vision (ISCEV) provides guidance for calibration and verification of stimulus and recording systems specific to clinical electrophysiology of vision. This guideline provides additional information for those using ISCEV Standards and Extended protocols and supersedes earlier Guidelines. The ISCEV guidelines for calibration and verification of stimuli and recording instruments (2023 update) were approved by the ISCEV Board of Directors 01, March 2023

Predictors of failed attendances in a multi-specialty outpatient centre using electronic databases.

BACKGROUND: Failure to keep outpatient medical appointments results in inefficiencies and costs. The objective of this study is to show the factors in an existing electronic database that affect failed appointments and to develop a predictive probability model to increase the effectiveness of interventions. METHODS: A retrospective study was conducted on outpatient clinic attendances at Tan Tock Seng Hospital, Singapore from 2000 to 2004. 22864 patients were randomly sampled for analysis. The outcome measure was failed outpatient appointments according to each patient's latest appointment. RESULTS: Failures comprised of 21% of all appointments and 39% when using the patients' latest appointment. Using odds ratios from the mutliple logistic regression analysis, age group (0.75 to 0.84 for groups above 40 years compared to below 20 years), race (1.48 for Malays, 1.61 for Indians compared to Chinese), days from scheduling to appointment (2.38 for more than 21 days compared to less than 7 days), previous failed appointments (1.79 for more than 60% failures and 4.38 for no previous appointments, compared with less than 20% failures), provision of cell phone number (0.10 for providing numbers compared to otherwise) and distance from hospital (1.14 for more than 14 km compared to less than 6 km) were significantly associated with failed appointments. The predicted probability model's diagnostic accuracy to predict failures is more than 80%. CONCLUSION: A few key variables have shown to adequately account for and predict failed appointments using existing electronic databases. These can be used to develop integrative technological solutions in the outpatient clinic

Thin primary cutaneous melanomas

BACKGROUND Public awareness and education may lead to the detection of thinner melanomas, which may result in a decrease in morbidity and mortality rates. Which detection patterns, lesion, and patient characteristics are associated with early detection? METHODS Using the University of Michigan prospective melanoma database, the detection patterns, lesion characteristics, and patient characteristics of 1515 consecutive patients with in situ or invasive cutaneous melanomas were reviewed. Tumor thickness (measured in millimeters) was evaluated in relationship to detection patterns (patient, physician, spouse), lesion characteristics (change in color, size, shape/elevation, ulceration, bleeding, tenderness, itching), and patient characteristics (gender, skin type, number of atypical and clinically benign nevi, history of sunburn, personal and family history of melanoma). RESULTS Patient characteristics associated with early detection included female gender, at least one atypical nevus, greater than 20 clinically benign nevi, and/or a personal history of melanoma. Skin types I, II, and III, a history of sunburn, and/or a family history of melanoma were also associated with thinner lesions, but these associations were not statistically significant. Lesion characteristics associated with earlier detection included a change in color, size, shape/elevation, and/or itching. Physician-detected melanomas were significantly thinner than patient or spouse-detected lesions. CONCLUSIONS Educational campaigns should include increasing melanoma awareness in males and educating the public on the early signs and symptoms. Education should be directed at both high and low-risk groups. Physicians should consider performing total skin examinations routinely on patients. Although they detect a relatively small percentage of all melanomas, physicians detect significantly thinner lesions. Cancer 2002;95:1562–8. © 2002 American Cancer Society. DOI 10.1002/cncr.10880Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/34362/1/10880_ftp.pd

Randomised clinical trial: a leucine-metformin-sildenafil combination (NS-0200) vs placebo in patients with non-alcoholic fatty liver disease

BACKGROUND: Sirtuin 1 (Sirt1) is suppressed in non-alcoholic fatty liver disease (NAFLD), while its' stimulation or overexpression results in reduced disease severity in pre-clinical NAFLD models. Leucine allosterically activates Sirt1 and synergise with other Sirt/AMPK/NO pathway activators. We developed a triple combination of leucine, metformin and sildenafil (NS-0200), which was effective in a mouse model of non-alcoholic steatohepatitis (NASH). AIM: To report the results from a Phase 2, randomised clinical trial of of NS-0200 in 91 subjects with NAFLD (liver fat ≥15% by magnetic resonance imaging-proton-density fat fraction (MRI-PDFF)). METHODS: Subjects were randomised to placebo, low-dose (1.1 g leucine/0.5 g metformin/0.5 mg sildenafil) or high-dose NS-0200 (1.1 g leucine/0.5 g metformin/1.0 mg sildenafil) b.d. for 16 weeks; change in hepatic fat was assessed via MRI-PDFF, and lipid metabolism was assessed via changes in the lipidomic signature. Seventy subjects completed the trial and met a priori compliance criteria. Analyses were conducted on the full cohort and on those with alanine aminotransferase (ALT) values above median (50 U/L; n = 35). RESULTS: In the full cohort, active treatments did not separate from placebo. High dose NS-0200 reduced hepatic fat by 15.7% (relative change from baseline) in the high ALT group (P < 0.005) while low dose NS-0200 and placebo did not significantly change hepatic fat. Lipidomic analysis showed dose-responsive treatment effects in both overall and high ALT cohorts, with significant decreases in metabolically active lipids and up-regulation of fatty acid oxidation. CONCLUSION: These data support further evaluation of high-dose NS-0200 for treating NASH, especially in those with elevated ALT (NCT 02546609)

ACC/AHA/SCAI/AMA–Convened PCPI/NCQA 2013 Performance Measures for Adults Undergoing Percutaneous Coronary Intervention A Report of the American College of Cardiology/American Heart Association Task Force on Performance Measures, the Society for Cardiovascular Angiography and Interventions, the American Medical Association–Convened Physician Consortium for Performance Improvement, and the National Committee for Quality Assurance

Journal of the American College of Cardiology Ó 2014 by the American College of Cardiology Foundation, American Heart Association, Inc., American Medical Association, and National Committee for Quality Assurance Published by Elsevier Inc. Vol. 63, No. 7, 2014 ISSN 0735-1097/$36.00 http://dx.doi.org/10.1016/j.jacc.2013.12.003 PERFORMANCE MEASURES ACC/AHA/SCAI/AMA–Convened PCPI/NCQA 2013 Performance Measures for Adults Undergoing Percutaneous Coronary Intervention A Report of the American College of Cardiology/American Heart Association Task Force on Performance Measures, the Society for Cardiovascular Angiography and Interventions, the American Medical Association–Convened Physician Consortium for Performance Improvement, and the National Committee for Quality Assurance Developed in Collaboration With the American Association of Cardiovascular and Pulmonary Rehabilitation and Mended Hearts Endorsed by the American Association of Cardiovascular and Pulmonary Rehabilitation and Mended Hearts WRITING COMMITTEE MEMBERS Brahmajee K. Nallamothu, MD, MPH, FACC, FAHA, Co-Chair*; Carl L. Tommaso, MD, FACC, FAHA, FSCAI, Co-Chairy; H. Vernon Anderson, MD, FACC, FAHA, FSCAI*; Jeffrey L. Anderson, MD, FACC, FAHA, MACP*; Joseph C. Cleveland, J R , MDz; R. Adams Dudley, MD, MBA; Peter Louis Duffy, MD, MMM, FACC, FSCAIy; David P. Faxon, MD, FACC, FAHA*; Hitinder S. Gurm, MD, FACC; Lawrence A. Hamilton, Neil C. Jensen, MHA, MBA; Richard A. Josephson, MD, MS, FACC, FAHA, FAACVPRx; David J. Malenka, MD, FACC, FAHA*; Calin V. Maniu, MD, FACC, FAHA, FSCAIy; Kevin W. McCabe, MD; James D. Mortimer, Manesh R. Patel, MD, FACC*; Stephen D. Persell, MD, MPH; John S. Rumsfeld, MD, PhD, FACC, FAHAjj; Kendrick A. Shunk, MD, PhD, FACC, FAHA, FSCAI*; Sidney C. Smith, J R , MD, FACC, FAHA, FACP{; Stephen J. Stanko, MBA, BA, AA#; Brook Watts, MD, MS *ACC/AHA Representative. ySociety of Cardiovascular Angiography and Interventions Representative. zSociety of Thoracic Surgeons Representative. xAmerican Association of Cardiovascular and Pulmonary Rehabilitation Representative. kACC/AHA Task Force on Performance Measures Liaison. {National Heart Lung and Blood Institute Representative. #Mended Hearts Representative. The measure specifications were approved by the American College of Cardiology Board of Trustees, American Heart Association Science Advisory and Coordinating Committee, in January 2013 and the American Medical Association–Physician Consortium for Performance Improvement in February 2013. This document was approved by the American College of Cardiology Board of Trustees and the American Heart Association Science Advisory and Coordinating Committee in October 2013, and the Society of Cardiovascular Angiography and Interventions in December 2013. The American College of Cardiology requests that this document be cited as follows: Nallamothu BK, Tommaso CL, Anderson HV, Anderson JL, Cleveland JC, Dudley RA, Duffy PL, Faxon DP, Gurm HS, Hamilton LA, Jensen NC, Josephson RA, Malenka DJ, Maniu CV, McCabe KW, Mortimer JD, Patel MR, Persell SD, Rumsfeld JS, Shunk KA, Smith SC, Stanko SJ, Watts B. ACC/AHA/SCAI/AMA–Convened PCPI/NCQA 2013 perfor- mance measures for adults undergoing percutaneous coronary intervention: a report of the American College of Cardiology/American Heart Association Task Force on Performance Measures, the Society for Cardiovascular Angiography and Interventions, the American Medical Association–Convened Physician Consortium for Performance Improvement, and the National Committee for Quality Assurance. J Am Coll Cardiol 2014;63:722–45. This article has been copublished in Circulation. Copies: This document is available on the World Wide Web sites of the American College of Cardiology (www.cardiosource.org) and the American Heart Asso- ciation (http://my.americanheart.org). For copies of this document, please contact Elsevier Inc. Reprint Department, fax (212) 633-3820, e-mail [email protected]. Permissions: Multiple copies, modification, alteration, enhancement, and/or distribution of this document are not permitted without the express permission of the American College of Cardiology. Requests may be completed online via the Elsevier site (http://www.elsevier.com/authors/obtaining- permission-to-re-use-elsevier-material). This Physician Performance Measurement Set (PPMS) and related data specifications were developed by the Physician Consortium for Performance Improvement (the Consortium), including the American College of Cardiology (ACC), the American Heart Association (AHA), and the American Medical Association (AMA), to facilitate quality-improvement activities by physicians. The performance measures contained in this PPMS are not clinical guidelines, do not establish a standard of medical care, and have not been tested for all potential applications. Although copyrighted, they can be reproduced and distributed, without modification, for noncommercial purposesdfor example, use by health care pro