The use of mechanical restraint and seclusion in patients with schizophrenia: A comparison of the practice in Germany and Switzerland

BACKGROUND: The use of coercive measures is an indicator of the quality of psychiatric inpatient treatment. To date, there is no data available to European comparisons on the incidence of such measures. METHODS: The frequency and duration of mechanical restraint and seclusion on patients with a diagnosis of F2 ICD-10 was analysed in seven German and seven Swiss psychiatric hospitals in the year 2004 using three indicators. Differences between German and Swiss hospitals regarding the indicators were tested for statistical significance using Mann-Whitney-U-tests. RESULTS: 6.6 % (Switzerland) and 10.4 % (Germany) of admissions respectively were affected by mechanical restraint and 17.8 % (Switzerland) and 7.8 % (Germany) respectively by seclusion. Seclusion as well as mechanical restraint per case were applied significantly more often in German than in Swiss hospitals and were of significantly longer duration in Swiss than in German hospitals. CONCLUSION: The results showed different patterns in the use of seclusion and mechanical restraint across Swiss and German hospitals. For future European research on the use of compulsory measures in routine psychiatric care, there is a need for uniformed definitions, reliable documentation of coercive measures as well as for an identical way of data analysis. To meet these conditions is the first step to achieve European standards for the use of coercive measures

SIL1 deficiency causes degenerative changes of peripheral nerves and neuromuscular junctions in fish, mice and human.

BACKGROUND: Marinesco-Sjögren Syndrome (MSS) is a rare neuromuscular condition caused by recessive mutations in the SIL1 gene resulting in the absence of functional SIL1 protein, a co-chaperone for the major ER chaperone, BiP. As BiP is decisive for proper protein processing, loss of SIL1 results in the accumulation of misshaped proteins. This accumulation likely damages and destroys cells in vulnerable tissues, leading to congenital cataracts, cerebellar ataxia, vacuolar myopathy and other MSS phenotypes. Whether the peripheral nervous system (PNS) is affected in MSS has not been conclusively shown. METHODS: To study PNS vulnerability in MSS, intramuscular nerves fibres from MSS patients and from SIL1-deficient mice (woozy) as well as sciatic nerves and neuromuscular junctions (NMJ) from these mice have been investigated via transmission electron microscopic and immunofluorescence studies accompanied by transcript studies and unbiased proteomic profiling. In addition, PNS and NMJ integrity were analyzed via immunofluorescence studies in an MSS-zebrafish model which has been generated for that purpose. RESULTS: Electron microscopy revealed morphological changes indicative of impaired autophagy and mitochondrial maintenance in distal axons and in Schwann cells. Moreover, changes of the morphology of NMJs as well as of transcripts encoding proteins important for NMJ function were detected in woozy mice. These findings were in line with a grossly abnormal structure of NMJs in SIL1-deficient zebrafish embryos. Proteome profiling of sciatic nerve specimens from woozy mice revealed altered levels of proteins implicated in neuronal maintenance suggesting the activation of compensatory mechanisms. CONCLUSION: Taken together, our combined data expand the spectrum of tissues affected by SIL1-loss and suggest that impaired neuromuscular transmission might be part of MSS pathophysiology

ATP synthase deficiency due to TMEM70 mutation leads to ultrastructural mitochondrial degeneration and is amenable to treatment.

TMEM70 is involved in the biogenesis of mitochondrial ATP synthase and mutations in the TMEM70 gene impair oxidative phosphorylation. Herein, we report on pathology and treatment of ATP synthase deficiency in four siblings. A consanguineous family of Roma (Gipsy) ethnic origin gave birth to 6 children of which 4 were affected presenting with dysmorphic features, failure to thrive, cardiomyopathy, metabolic crises, and 3-methylglutaconic aciduria as clinical symptoms. Genetic testing revealed a homozygous mutation (c.317-2A>G) in the TMEM70 gene. While light microscopy was unremarkable, ultrastructural investigation of muscle tissue revealed accumulation of swollen degenerated mitochondria with lipid crystalloid inclusions, cristae aggregation, and exocytosis of mitochondrial material. Biochemical analysis of mitochondrial complexes showed an almost complete ATP synthase deficiency. Despite harbouring the same mutation, the clinical outcome in the four siblings was different. Two children died within 60 h after birth; the other two had recurrent life-threatening metabolic crises but were successfully managed with supplementation of anaplerotic amino acids, lipids, and symptomatic treatment during metabolic crisis. In summary, TMEM70 mutations can cause distinct ultrastructural mitochondrial degeneration and almost complete deficiency of ATP synthase but are still amenable to treatment

Convergent Sets of Data from In Vivo and In Vitro Methods Point to an Active Role of Hsp60 in Chronic Obstructive Pulmonary Disease Pathogenesis

BACKGROUND: It is increasingly clear that some heat shock proteins (Hsps) play a role in inflammation. Here, we report results showing participation of Hsp60 in the pathogenesis of chronic obstructive pulmonary diseases (COPD), as indicated by data from both in vivo and in vitro analyses. METHODS AND RESULTS: Bronchial biopsies from patients with stable COPD, smoker controls with normal lung function, and non-smoker controls were studied. We quantified by immunohistochemistry levels of Hsp10, Hsp27, Hsp40, Hsp60, Hsp70, Hsp90, and HSF-1, along with levels of inflammatory markers. Hsp10, Hsp40, and Hsp60 were increased during progression of disease. We found also a positive correlation between the number of neutrophils and Hsp60 levels. Double-immunostaining showed that Hsp60-positive neutrophils were significantly increased in COPD patients. We then investigated in vitro the effect on Hsp60 expression in bronchial epithelial cells (16HBE) caused by oxidative stress, a hallmark of COPD mucosa, which we induced with H\u2082O\u2082. This stressor determined increased levels of Hsp60 through a gene up-regulation mechanism involving NFkB-p65. Release of Hsp60 in the extracellular medium by the bronchial epithelial cells was also increased after H\u2082O\u2082 treatment in the absence of cell death. CONCLUSIONS: This is the first report clearly pointing to participation of Hsps, particularly Hsp60, in COPD pathogenesis. Hsp60 induction by NFkB-p65 and its release by epithelial cells after oxidative stress can have a role in maintaining inflammation, e.g., by stimulating neutrophils activity. The data open new scenarios that might help in designing efficacious anti-inflammatory therapies centered on Hsp60 and applicable to COP

Acute mountain sickness.

Acute mountain sickness (AMS) is a clinical syndrome occurring in otherwise healthy normal individuals who ascend rapidly to high altitude. Symptoms develop over a period ofa few hours or days. The usual symptoms include headache, anorexia, nausea, vomiting, lethargy, unsteadiness of gait, undue dyspnoea on moderate exertion and interrupted sleep. AMS is unrelated to physical fitness, sex or age except that young children over two years of age are unduly susceptible. One of the striking features ofAMS is the wide variation in individual susceptibility which is to some extent consistent. Some subjects never experience symptoms at any altitude while others have repeated attacks on ascending to quite modest altitudes. Rapid ascent to altitudes of 2500 to 3000m will produce symptoms in some subjects while after ascent over 23 days to 5000m most subjects will be affected, some to a marked degree. In general, the more rapid the ascent, the higher the altitude reached and the greater the physical exertion involved, the more severe AMS will be. Ifthe subjects stay at the altitude reached there is a tendency for acclimatization to occur and symptoms to remit over 1-7 days

A scalable semantic framework for IoT healthcare applications

International audienceIoT-based systems for early epidemic detection have not been investigated yet in the research. The state-of-the art in sensor technology and activity recognition makes it possible to automatically detect Activities of Daily Living (ADL). Semantic reasoning over ADLs can discover anomalies and symptoms for disorders, hence diseases and epidemics. However, semantic reasoning is computationally rather expensive and therefore unusable for real-time monitoring in large scale applications, like early epidemic detection. To overcome this limitation, this paper proposes a new scalable semantic framework based on several semantic reasoning techniques that are distributed over a semantic middleware. To reduce the number of events to process during the semantic reasoning, a Complex Event Processing (CEP) engine is used to detect abnormal events in ADL and to generate the associated symptom indicators. To demonstrate real-time detection and scalability, the proposed framework integrates a new extension of ADLSim, a discrete event simulator that simulates long-term sequences of ADL

A scalable semantic framework for IoT healthcare applications

International audienceIoT-based systems for early epidemic detection have not been investigated yet in the research. The state-of-the art in sensor technology and activity recognition makes it possible to automatically detect Activities of Daily Living (ADL). Semantic reasoning over ADLs can discover anomalies and symptoms for disorders, hence diseases and epidemics. However, semantic reasoning is computationally rather expensive and therefore unusable for real-time monitoring in large scale applications, like early epidemic detection. To overcome this limitation, this paper proposes a new scalable semantic framework based on several semantic reasoning techniques that are distributed over a semantic middleware. To reduce the number of events to process during the semantic reasoning, a Complex Event Processing (CEP) engine is used to detect abnormal events in ADL and to generate the associated symptom indicators. To demonstrate real-time detection and scalability, the proposed framework integrates a new extension of ADLSim, a discrete event simulator that simulates long-term sequences of ADL

Beyond vacuolar pathology: Multiomic profiling of Danon disease reveals dysfunctional mitochondrial homeostasis.

Funder: Ministerium für Kultur und Wissenschaft des Landes Nordrhein‐Westfalen; doi: http://dx.doi.org/10.13039/501100014690Funder: Regierenden Bürgermeister von Berlin ‐ Senatskanzlei Wissenschaft und ForschungFunder: European Regional Development Fund; doi: http://dx.doi.org/10.13039/50110000853