Expression of decitabine-targeted oncogenes in meningiomas in vivo

Neurosurgical Review - Treatment of meningiomas refractory to surgery and irradiation is challenging and effective chemotherapies are still lacking. Recently, in vitro analyses revealed decitabine...     

Quantification of tonic and phasic muscle activity in REM sleep behavior disorder.

REM sleep behavior disorder (RBD) is characterized by excessive tone of the chin muscle and limb movement during sleep. In the past, quantification of increased muscle tone in REM sleep has been performed visually, using no stringent criteria. The aim of this study was to develop an automatic analysis, allowing the quantification of muscle activity and its amplitude for all sleep stages, with a focus on REM sleep in patients with RBD. Forty-eight patients (27 male, 21 female) with RBD were included in the analysis. Twenty-one had idiopathic RBD; 28 had narcolepsy plus RBD. Twenty-five patients without confirmed sleep disorder served as control subjects. The amplitude of the EMG was generated from the difference of the upper and lower envelope of the mentalis muscle recordings. By smoothing the amplitude curve, a threshold curve was defined. Any muscle activity beyond the threshold curve was defined as motor activity. The means of the motor activity per second were summarized statistically and calculated for each sleep stage. Due to variable distribution of REM sleep, the latter was assigned to respective quartiles of the recorded night. Muscle activity was defined according to a histogram as short-lasting (<0.5 second) and long-lasting (>0.5 second) activity. No difference in the distribution of REM sleep/quartile and mean muscle tone throughout the sleep cycle could be found within the RBD groups and control subjects. Muscle activity was in the range of 200 ms. No clusters or regular distribution of muscle activity were found. Long muscle activity in the group with manifest clinical RBD was significantly higher than in control subjects, whereas it was nonsignificantly higher in subclinical RBD. The correlation between the frequency of long muscle activity in REM sleep and age was highly significant only for patients with idiopathic RBD. Automatic analysis of muscle activity in sleep is a reliable, easy method that may easily be used in the evaluation for REM sleep behavior disorder, creating indices of muscle activity similar to the indices for sleep apnea or PLMS. Together with the overt behavior, the analyses provides an important tool to get a deeper insight into the pathophysiology of RBD. Long movements appear to represent the motor disinhibition in REM sleep more distinct than short movements. The positive correlation of age and increased motor activity in REM sleep in idiopathic RBD highlights the idea of age dependant motor disinhibition as a continuum of a neurodegenerative disorder, which in narcolepsy patients with RBD only seems to happen as a single temporal event at onset of the disorder.     

Messung von Schlafdauer und Schlafqualit?t

Restorative functions of sleep are of special interest for sleep medicine. For the assessment of these restorative functions, various parameters are taken into account, among which sleep duration and sleep quality play the most important roles. Both terms are essential for sleep perception, expressing the subjective satisfaction of the individual with the time spent asleep. In recent decades, sleep medicine and sleep research have developed methods for the assessment of both objective and subjective dimensions of sleep. Among subjective methods, taking of the medical history focusing on the patient's sleep is important. Standardized and validated questionnaires play a supportive role. Objective methods are, for example, estimation of the sleep-wake cycle by means of actigraphy and polygraphy. Especially in multimorbid patients, polysomnography is still the gold standard method for diagnostics. An important approach during recent years is shifting from bothering overnight examinations into less disturbing procedures for patients that include performing ambulatory, outpatient examinations in the patients' home rather than inpatient surveillance within sleep centers.     

TRPM7 Is Required for Breast Tumor Cell Metastasis

TRPM7 encodes a Ca(2+)-permeable nonselective cation channel with kinase activity. TRPM7 has been implicated in control of cell adhesion and migration, but whether TRPM7 activity contributes to cancer progression has not been established. Here we report that high levels of TRPM7 expression independently predict poor outcome in breast cancer patients and that it is functionally required for metastasis formation in a mouse xenograft model of human breast cancer. Mechanistic investigation revealed that TRPM7 regulated myosin II-based cellular tension, thereby modifying focal adhesion number, cell-cell adhesion and polarized cell movement. Our findings therefore suggest that TRPM7 is part of a mechanosensory complex adopted by cancer cells to drive metastasis formation. Cancer Res; 72(16); 4250-61. ?2012 AACR.     

Quantitative investigation of additional mask leakage during CPAP therapy

Objectives

The occurrence of mask leakages during the administration of nasal continuous positive airway pressure (CPAP) therapy for treating obstructive sleep apnoea syndrome (OSAS) leads to decreased compliance. Because of exhalation valves, all mask systems have a predefined amount of systematic mask leakage, thereby complicating measurement of any additional spontaneous leakage occurring during the night. In fact, relatively few studies have investigated the impact and amount of mask leakage in patients using CPAP.

Methods

Using a fourth-order polynomial, systematic leakage was modelled as the nonlinear relationship between mask pressure and leakage through the exhalation valves. The total leakage was measured in 22 patients, and additional leakage was calculated by subtracting the systematic from the measured total leakage during the night.

Results

A mean additional leakage of 6.9±7.4 l/min was found; however, some patients showed rather high mask leakages (up to 37.4 l/min) with high mask pressures, possibly indicating that not all nasal masks are equally suited for higher CPAP pressures.

Conclusions

The relevant mask leakages that were observed in some cases stress the importance of thorough monitoring of patients receiving CPAP therapy. Furthermore, all investigated patients were trained very extensively in our sleep lab, possibly indicating that intensive training may be an important factor for the rather low additional mask leakages.     

A gene signature for late distant metastasis in breast cancer identifies a potential mechanism of late recurrences

Introduction

Breast cancer risk of recurrence is known to span 20 years, yet existing prognostic signatures are best at predicting early recurrences (≤5 years). There is a critical need to identify those patients at risk of late‐relapse (>5 years), in order to select potential candidates for further treatment and to identify molecular targets for such treatment.

Methods

A total of 252 breast primary tumors were selected at the Netherlands Cancer Institute from a retrospective series of ER+, HER2− breast cancer patients with a follow‐up of at least 10 years. Gene expression analysis was performed using Agilent 4x44K microarrays. Patients were classified in 3 groups: no relapse (M0); relapse before 5 years (M0‐5) or after 5 years (M5‐15). We assessed the correlation of clinico‐pathological variables with late Distant Metastases (DM). We divided the patient series into a training set of untreated patients (n = 140) and a test set of treated patients (n = 112), to investigate whether a gene‐signature or single genes could be identified for predicting late DM. Pathway level late DM correlates were identified using PARADIGM and DAVID.

Results

Of the clinico‐pathologic variables tested, only lymph node status associated with late DM. A 241‐gene signature developed on the NKI training set was able to classify M5‐15 patients in the test set with a sensitivity of 77% and a specificity of 33% (AUC 0.654). This signature showed enrichment in genes involved in immune response and extracellular matrix. An alternative analysis of individual genes identified CH25H as an independent predictor of distant metastasis in our patient series.

Conclusions

We identified a gene signature for late metastasis in breast cancer. Our data are consistent with a model in which suppressed anti‐tumoral immunity enables dormant tumor cells to re‐enter the cell cycle to form metastases in response to extrinsic events in the microenvironment.     

Induction of tissue factor expression by anti-β2-glycoprotein I is mediated by tumor necrosis factor α

Journal of Thrombosis and Thrombolysis - Antiphospholipid antibodies (aPL) are heterogeneous and there is evidence that binding specificity determines which cellular effects they can trigger. We...     

艾滋病病人下肢脓肿两例治疗体会

据世界卫生组织的报道，卢旺达是艾滋病的高发地区，艾滋病毒携带者为8％-16％。这里规定不允许给所有的病人做HIV化验检查，也不允许做常规检验，只有病人同意或病情需要时才能在专门机构进行检查，所以潜在的艾滋病病毒时时刻刻都在威胁着医护人员的安全。笔者所在的援助非洲医疗队在卢旺达基本古医院开展医疗救治时收治了2例艾滋病下肢感染脓肿病人，并对其实施了手术治疗。本文对这两例的具体特点及治疗介绍如下。     

Antiphospholipid antibody‐induced cellular responses depend on epitope specificity : implications for treatment of antiphospholipid syndrome

Essentials

• Antiphospholipid antibodies (aPL) are heterogeneous and induce different cellular responses.
• We analyzed signaling events induced by different monoclonal and patient aPL in monocytes.
• Two major signaling pathways involving either NADPH‐oxidase or LRP8 were identified.
• Our data suggest that these two pathways mediate the majority of aPL effects on monocytes.