Nightmares affect the experience of sleep quality but not sleep architecture: an ambulatory polysomnographic study

Background: Nightmares and bad dreams are common in people with emotional disturbances. For example, nightmares are a core symptom in posttraumatic stress disorder and about 50% of borderline personality disorder patients suffer from frequent nightmares. Independent of mental disorders, nightmares are often associated with sleep problems such as prolonged sleep latencies, poorer sleep quality, and daytime sleepiness. It has not been well documented whether this is reflected in objectively quantifiable physiological indices of sleep quality. Methods: Questionnaires regarding subjective sleep quality and ambulatory polysomnographic recordings of objective sleep parameters were collected during three consecutive nights in 17 individuals with frequent nightmares (NM) and 17 healthy control participants (HC). Results: NM participants reported worse sleep quality, more waking problems and more severe insomnia compared to HC group. However, sleep measures obtained by ambulatory polysomnographic recordings revealed no group differences in (a) overall sleep architecture, (b) sleep cycle duration as well as REM density and REM duration in each cycle and (c) sleep architecture when only nights with nightmares were analyzed. Conclusions: Our findings support the observation that nightmares result in significant impairment which is independent from disturbed sleep architecture. Thus, these specific problems require specific attention and appropriate treatment

Detection of Cerebrospinal Fluid Neurofilament Light Chain as a Marker for Alpha-Synucleinopathies

Alpha-synucleinopathies, such as Parkinson's disease (PD), dementia with Lewy bodies (DLB), and multiple system atrophy (MSA), are a class of neurodegenerative diseases. A diagnosis may be challenging because clinical symptoms partially overlap, and there is currently no reliable diagnostic test available. Therefore, we aimed to identify a suitable marker protein in cerebrospinal fluid (CSF) to distinguish either between different types of alpha-synucleinopathies or between alpha-synucleinopathies and controls. In this study, the regulation of different marker protein candidates, such as alpha-synuclein (a-Syn), neurofilament light chain (NfL), glial fibrillary acidic protein (GFAP), and total tau (tau) in different types of alpha-synucleinopathies, had been analyzed by using an ultrasensitive test system called single-molecule array (SIMOA). Interestingly, we observed that CSF-NfL was significantly elevated in patients with DLB and MSA compared to patients with PD or control donors. To differentiate between groups, receiver operating characteristic (ROC) curve analysis resulted in a very good diagnostic accuracy as indicated by the area under the curve (AUC) values of 0.87-0.92 for CSF-NfL. Furthermore, we observed that GFAP and tau were slightly increased either in DLB or MSA, while a-Syn levels remained unregulated. Our study suggests NfL as a promising marker to discriminate between different types of alpha-synucleinopathies or between DLB/MSA and controls

Thyroid and hepatic function after high-dose 131 I-metaiodobenzylguanidine ( 131 I-MIBG) therapy for neuroblastoma.

Background 131 I-Metaiodobenzylguanidine ( 131 I-MIBG) provides targeted radiotherapy for children with neuroblastoma, a malignancy of the sympathetic nervous system. Dissociated radioactive iodide may concentrate in the thyroid, and 131 I-MIBG is concentrated in the liver after 131 I-MIBG therapy. The aim of our study was to analyze the effects of 131 I-MIBG therapy on thyroid and liver function. Procedure Pre- and post-therapy thyroid and liver functions were reviewed in a total of 194 neuroblastoma patients treated with 131 I-MIBG therapy. The cumulative incidence over time was estimated for both thyroid and liver toxicities. The relationship to cumulative dose/kg, number of treatments, time from treatment to follow-up, sex, and patient age was examined. Results In patients who presented with Grade 0 or 1 thyroid toxicity at baseline, 12 ± 4% experienced onset of or worsening to Grade 2 hypothyroidism and one patient developed Grade 2 hyperthyroidism by 2 years after 131 I-MIBG therapy. At 2 years post- 131 I-MIBG therapy, 76 ± 4% patients experienced onset or worsening of hepatic toxicity to any grade, and 23 ± 5% experienced onset of or worsening to Grade 3 or 4 liver toxicity. Liver toxicity was usually transient asymptomatic transaminase elevation, frequently confounded by disease progression and other therapies. Conclusion The prophylactic regimen of potassium iodide and potassium perchlorate with 131 I-MIBG therapy resulted in a low rate of significant hypothyroidism. Liver abnormalities following 131 I-MIBG therapy were primarily reversible and did not result in late toxicity. 131 I-MIBG therapy is a promising treatment for children with relapsed neuroblastoma with a relatively low rate of symptomatic thyroid or hepatic dysfunction. Pediatr Blood Cancer 2011;56:191–201. © 2010 Wiley-Liss, Inc.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/78497/1/22767_ftp.pd

Taking into account sensory knowledge: the case of geo-techologies for children with visual impairments

This paper argues for designing geo-technologies supporting non-visual sensory knowledge. Sensory knowledge refers to the implicit and explicit knowledge guiding our uses of our senses to understand the world. To support our argument, we build on an 18 months field-study on geography classes for primary school children with visual impairments. Our findings show (1) a paradox in the use of non-visual sensory knowledge: described as fundamental to the geography curriculum, it is mostly kept out of school; (2) that accessible geo-technologies in the literature mainly focus on substituting vision with another modality, rather than enabling teachers to build on children's experiences; (3) the importance of the hearing sense in learning about space. We then introduce a probe, a wrist-worn device enabling children to record audio cues during field-trips. By giving importance to children's hearing skills, it modified existing practices and actors' opinions on non-visual sensory knowledge. We conclude by reflecting on design implications, and the role of technologies in valuing diverse ways of understanding the world

Molecular basis of diseases caused by the mtDNA mutation m.8969G>A in the subunit a of ATP synthase

The ATP synthase which provides aerobic eukaryotes with ATP, organizes into a membrane-extrinsic catalytic domain, where ATP is generated, and a membrane-embedded FO domain that shuttles protons across the membrane. We previously identified a mutation in the mitochondrial MT-ATP6 gene (m.8969G>A) in a 14-year-old Chinese female who developed an isolated nephropathy followed by brain and muscle problems. This mutation replaces a highly conserved serine residue into asparagine at amino acid position 148 of the membrane-embedded subunit a of ATP synthase. We showed that an equivalent of this mutation in yeast (aS175N) prevents FO-mediated proton translocation. Herein we identified four first-site intragenic suppressors (aN175D, aN175K, aN175I, and aN175T), which, in light of a recently published atomic structure of yeast FO indicates that the detrimental consequences of the original mutation result from the establishment of hydrogen bonds between aN175 and a nearby glutamate residue (aE172) that was proposed to be critical for the exit of protons from the ATP synthase towards the mitochondrial matrix. Interestingly also, we found that the aS175N mutation can be suppressed by second-site suppressors (aP12S, aI171F, aI171N, aI239F, and aI200M), of which some are very distantly located (by 20-30 Å) from the original mutation. The possibility to compensate through long-range effects the aS175N mutation is an interesting observation that holds promise for the development of therapeutic molecules

High-redshift lensed galaxies

We present the results obtained from our deep survey of lensing clusters aimed at constraining the abundance of star-forming galaxies at z∼6-1

Corpse Engulfment Generates a Molecular Memory that Primes the Macrophage Inflammatory Response

Macrophages are multifunctional cells that perform diverse roles in health and disease. Emerging evidence has suggested that these innate immune cells might also be capable of developing immunological memory, a trait previously associated with the adaptive system alone. While recent studies have focused on the dramatic macrophage reprogramming that follows infection and protects against secondary microbial attack, can macrophages also develop memory in response to other cues? Here, we show that apoptotic corpse engulfment by Drosophila macrophages is an essential primer for their inflammatory response to tissue damage and infection in vivo. Priming is triggered via calcium-induced JNK signaling, which leads to upregulation of the damage receptor Draper, thus providing a molecular memory that allows the cell to rapidly respond to subsequent injury or infection. This remarkable plasticity and capacity for memory places macrophages as key therapeutic targets for treatment of inflammatory disorders

Transcriptional profiling of rat hypothalamus response to 2,3,7,8-tetrachlorodibenzo-p-dioxin

In some mammals, halogenated aromatic hydrocarbon (HAH) exposure causes wasting syndrome, defined as significant weight loss associated with lethal outcomes. The most potent HAH in causing wasting is 2,3,7,8-tetrachlorodibenzo-rho-dioxin (TCDD), which exerts its toxic effects through the aryl hydrocarbon receptor (AHR). Since TCDD toxicity is thought to predominantly arise from dysregulation of AHR-transcribed genes, it was hypothesized that wasting syndrome is a result of to TCDD-induced dysregulation of genes involved in regulation of food-intake. As the hypothalamus is the central nervous systems' regulatory center for food-intake and energy balance. Therefore, mRNA abundances in hypothalamic tissue from two rat strains with widely differing sensitivities to TCDD-induced wasting syndrome: TCDD-sensitive Long-Evans rats and TCDD-resistant Han/Wistar rats, 23 h after exposure to TCDD (100 mu g/kg) or corn oil vehicle. TCDD exposure caused minimal transcriptional dysregulation in the hypothalamus, with only 6 genes significantly altered in Long-Evans rats and 15 genes in Han/Wistar rats. Two of the most dysregulated genes were Cyp1a1 and Nqo1, which are induced by TCDD across a wide range of tissues and are considered sensitive markers of TCDD exposure. The minimal response of the hypothalamic transcriptome to a lethal dose of TCDD at an early time-point suggests that the hypothalamus is not the predominant site of initial events leading to hypophagia and associated wasting. TCDD may affect feeding behaviour via events upstream or downstream of the hypothalamus, and further work is required to evaluate this at the level of individual hypothalamic nuclei and subregions. (C) 2014 The Authors. Published by Elsevier Ireland Ltd.Peer reviewe

Testing the relative sensitivity of 102 ecological variables as indicators of woodland condition in the New Forest, UK.

Forests globally are facing an increasing number of threats from modified disturbance regimes, novel stressors and changing environmental conditions. This has ultimately resulted in declines in the ecological condition of many forest and woodland ecosystems, leading to widespread tree mortality and stand dieback. Effective indicators of overall woodland ecological condition are therefore needed for environmental monitoring and to support management responses. To test the effectiveness of different variables that could potentially be used as indicators of woodland condition, 102 variables that describe woodland structure, composition, functioning, edaphic conditions and disturbance regimes were assessed along 12 replicate gradients of beech stand dieback. Results indicated that 35 variables differed significantly between at least two stages of the dieback gradient, indicating their sensitivity to stand dieback. Seven of these indicators related to woodland species composition, two to functional processes, 20 to structural features, four to edaphic conditions, and two to disturbance regimes. These results demonstrate that effective indicators can potentially be identified for each of the ecological categories. Effective composition indicators included species richness of ectomycorrhizal fungi, ground flora and epiphytic lichens; functional indicators were soil respiration rate and net nitrification rate; edaphic conditions included soil Na:Ca ratio, exchangeable sodium, total carbon, Ca:Al ratio; structural indicators included canopy openness, litter cover, sward height, and volume of deadwood, and for disturbance the indicator was Equus dung density. Other measures, such as shrub cover and species richness of carabid beetles and spiders, were not found to vary significantly along the dieback gradients, and were therefore not identified as effective indicators. These results demonstrate the value of gradient analysis for evaluating indicators of woodland condition, but also highlight the need for multi-site studies to identify indicators with widescale applicability