Markovian analysis of phasic measures of REM sleep in normal, depressed, and schizophrenic subjects

Rapid eye movement (REM) phasic activity refers to brief events that occur in periods of REM sleep, such as individual eye movements (EMs). REM density (RD) is the bestknown measure of such activity, although reports of RD differences among normal, depressed, and schizophrenic subjects have been equivocal. RD is a measure with a large variability, and its physiological substrate is not known. We sought a more consistent measure which might also suggest the underlying physiology. Using the time intervals between individual EMs, we calculated empirical probability distributions which showed that EMs fell into two subgroups or states: "burst" and "isolated". Then, a novel Markov chain model of sequential transition between the states was calculated for nine normal, eight schizophrenic, and seven depressed male veterans. A significantly higher probability of remaining in the burst state was observed in both patient groups. The actual number of EMs in the isolated state was nearly identical in the three groups. Possible pontine neurochemical explanations involving cholinergic and serotonergic mechanisms are discussed.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/30151/1/0000528.pd

Recent Studies in Andean Prehistory and Protohistory: Papers from the Second Annual Northeast Conference on Andean Archaeology and Ethnohistory

The contributions in this volume represent nine of the twenty-three papers presented at the Second Annual Northeast Conference on Andean Archaeology and Ethnohistory (NCAAE) held at the American Museum of Natural History on November 19-20, 1983. Papers include The Preceramic and Formative Period Occupations in the Cordillera Negra: Preliminary Report by Michael A. Malpass, The Early Horizon--Early Intermediate Period Transition: A View from the Nepena and Viru Valleys by Richard E. Daggett, Paracas in Chincha and Pisco: A Reappraisal of the Ocucaje Sequence by Dwight T. Wallace, Impressions in Metal: Reconstructing Burial Context at Loma Negra, Peru by Anne-Louise Schaeffer, The Moche Moon by Elizabeth P. Benson, Archaeological Investigation in the Andean Piedmont and High Llanos of Western Venezuela: A Preliminary Report by Charles S. Spencer and Elsa M. Redmond, Pachacamac--An Andean Oracle Under Inca Rule by Thomas C. Patterson, The Spanish League and Inca Sites: A Reassessment of the Itinerary of Juan de Matienzo through N.W. Argentina by Gordon C. Pollard, and Written Sources on Andean Cosmogony by George Kubler.https://digitalcommons.library.umaine.edu/andean_past_special/1001/thumbnail.jp

Hereditary transthyretin amyloidosis: baseline characteristics of patients in the NEURO-TTR trial

Background: Hereditary transthyretin (ATTRm) amyloidosis is a rare, progressive and fatal disease with a range of clinical manifestations.Objective: This study comprehensively evaluates disease characteristics in a large, diverse cohort of patients with ATTRm amyloidosis.Methods: Adult patients (N = 172) with Stage 1 or Stage 2 ATTRm amyloidosis who had polyneuropathy were screened and enrolled across 24 investigative sites and 10 countries in the NEURO-TTR trial (www.clinicaltrials.gov, NCT01737398). Medical and disease history, quality of life, laboratory data, and clinical assessments were analyzed.Results: The NEURO-TTR patient population was diverse in age, disease severity, TTR mutation, and organ involvement. Twenty-seven different TTR mutations were present, with Val30Met being the most common (52%). One third of patients reported early onset disease (before age 50) and the average duration of neuropathy symptoms was 5.3 years. Symptoms affected multiple organs and systems, with nearly 70% of patients exhibiting broad involvement of weakness, sensory loss, and autonomic disturbance. Over 60% of patients had cardiomyopathy, with highest prevalence in the United States (72%) and lowest in South America/Australasia (33%). Cardiac biomarker NT-proBNP correlated with left ventricular wall thickness (p<.001). Quality of life, measured by Norfolk QoL-DN and SF-36 patient-reported questionnaires, was significantly impaired and correlated with disease severity.Conclusions: Baseline data from the NEURO-TTR trial demonstrates ATTRm amyloidosis as a systemic disease with deficits in multiple organs and body systems, leading to decreased quality of life. We report concomitant presentation of polyneuropathy and cardiomyopathy in most patients, and early involvement of multiple body systems

Urine selenium concentration is a useful biomarker for assessing population level selenium status

Plasma selenium (Se) concentration is an established population level biomarker of Se status, especially in Se-deficient populations. Previously observed correlations between dietary Se intake and urinary Se excretion suggest that urine Se concentration is also a potentially viable biomarker of Se status. However, there are only limited data on urine Se concentration among Se-deficient populations. Here, we test if urine is a viable biomarker for assessing Se status among a large sample of women and children in Malawi, most of whom are likely to be Se-deficient based on plasma Se status. Casual (spot) urine samples (n = 1406) were collected from a nationally representative sample of women of reproductive age (WRA, n =741) and school aged children (SAC, n=665) across Malawi as part of the 2015/16 Demographic and Health Survey. Selenium concentration in urine was determined using inductively coupled plasma mass spectrometry (ICP-MS). Urinary dilution corrections for specific gravity, osmolality, and creatinine were applied to adjust for hydration status. Plasma Se status had been measured for the same survey participants. There was between-cluster variation in urine Se concentration that corresponded with variation in plasma Se concentration, but not between households within a cluster, or between individuals within a household. Corrected urine Se concentrations explained more of the between-cluster variation in plasma Se concentration than uncorrected data. These results provide new evidence that urine may be used in the surveillance of Se status at the population level in some groups. This could be a cost-effective option if urine samples are already being collected for other assessments, such as for iodine status analysis as in the Malawi and other national Demographic and Health Surveys

Inotersen preserves or improves quality of life in hereditary transthyretin amyloidosis

Objective: To examine the impact on quality of life (QOL) of patients with hATTR amyloidosis with polyneuropathy treated with inotersen (Tegsedi™) versus placebo. Methods: Data were from the NEURO-TTR trial (ClinicalTrials.gov Identifier: NCT01737398), a phase 3, multinational, randomized, double-blind, placebo-controlled study of inotersen in patients with hATTR amyloidosis with polyneuropathy. At baseline and week 66, QOL measures-the Norfolk-QOL-Diabetic Neuropathy (DN) questionnaire and SF-36v2® Health Survey (SF-36v2)-were assessed. Treatment differences in mean changes in QOL from baseline to week 66 were tested using mixed-effect models with repeated measures. Responder analyses compared the percentages of patients whose QOL meaningfully improved or worsened from baseline to week 66 in inotersen and placebo arms. Descriptive analysis of item responses examined treatment differences in specific activities and functions at week 66. Results: Statistically significant mean differences between treatment arms were observed for three of five Norfolk-QOL-DN domains and five of eight SF-36v2 domains, with better outcomes for inotersen than placebo in physical functioning, activities of daily living, neuropathic symptoms, pain, role limitations due to health problems, and social functioning. A larger percentage of patients in the inotersen arm than the placebo arm showed preservation or improvement in Norfolk-QOL-DN and SF-36v2 scores from baseline to week 66. Responses at week 66 showed more substantial problems with daily activities and functioning for patients in the placebo arm than in the inotersen arm. Conclusion: Patients with hATTR amyloidosis with polyneuropathy treated with inotersen showed preserved or improved QOL at 66 weeks compared to those who received placebo.This research was funded by Akcea Therapeutics and Ionis Pharmaceuticals, Incinfo:eu-repo/semantics/publishedVersio

A retinoic acid–dependent checkpoint in the development of CD4+ T cell–mediated immunity

Immune cell activation induces concurrent temporal and spatial retinoic acid signaling, and CD4+ T cell–specific loss of RA signals reduces effector function, migration, and polarity

Fish Oil and Fenofibrate for the Treatment of Hypertriglyceridemia in HIV-Infected Subjects on Antiretroviral Therapy: Results of ACTG A5186

Fish oil has been shown to reduce serum triglyceride (TG) concentrations. In HIV-infected patients on antiretroviral therapy, high TG concentrations likely contribute to increased risk of cardiovascular disease. AIDS Clinical Trials Group A5186 examined the safety and efficacy of fish oil plus fenofibrate in subjects not achieving serum TG levels ≤200 mg/dL with either agent alone