Routine immunohistochemical analysis of a conventional endomyocardial-biopsy sample appears to be a highly sensitive and specific diagnostic test for ARVC.

BackgroundClimate change in the Himalayas, a biodiversity hotspot, home of many sacred landscapes, and the source of eight largest rivers of Asia, is likely to impact the well-being of ∼20% of humanity. However, despite the extraordinary environmental, cultural, and socio-economic importance of the Himalayas, and despite their rapidly increasing ecological degradation, not much is known about actual changes in the two most critical climatic variables: temperature and rainfall. Nor do we know how changes in these parameters might impact the ecosystems including vegetation phenology.Methodology/Principal FindingsBy analyzing temperature and rainfall data, and NDVI (Normalized Difference Vegetation Index) values from remotely sensed imagery, we report significant changes in temperature, rainfall, and vegetation phenology across the Himalayas between 1982 and 2006. The average annual mean temperature during the 25 year period has increased by 1.5°C with an average increase of 0.06°C yr−1. The average annual precipitation has increased by 163 mm or 6.52 mmyr−1. Since changes in temperature and precipitation are immediately manifested as changes in phenology of local ecosystems, we examined phenological changes in all major ecoregions. The average start of the growing season (SOS) seems to have advanced by 4.7 days or 0.19 days yr−1 and the length of growing season (LOS) appears to have advanced by 4.7 days or 0.19 days yr−1, but there has been no change in the end of the growing season (EOS). There is considerable spatial and seasonal variation in changes in climate and phenological parameters.Conclusions/SignificanceThis is the first time that large scale climatic and phenological changes at the landscape level have been documented for the Himalayas. The rate of warming in the Himalayas is greater than the global average, confirming that the Himalayas are among the regions most vulnerable to climate change.

Extracranial metastasis is a unique but rare manifestation of glioblastoma multiforme. It is thought to arise from glioblastoma cells disseminated into the blood stream. We undertook a comprehensive analysis of 88 cases of extracranial glioblastoma (5 were gliosarcomas) published between 1928 and 2009. Cases included in the analysis were primary or secondary glioblastomas that subsequently invaded organs outside the brain or spinal cord. The median age was 38 years and the median overall survival time was 10.5 months (range 0.0-60.0 months). The median time from symptom onset to diagnosis of primary glioblastoma was 2.5 months, from diagnosis to detection of extracranial metastasis was 8.5 months, and from metastasis to death was 1.5 months. From 1940 to 2009, there has been progressive lengthening of the interval from detection of extracranial metastasis to death, at a rate of 0.7 months per decade (95% confidence interval 0.5-1.0 month). Use of magnetic resonance imaging correlates with an increase in overall survival but not age, gender, or site of primary glioblastoma. Patients treated with surgery + radiation + chemotherapy + cerebrospinal fluid shunting had the longest average survival interval from metastasis to death when compared to those treated with surgery alone, radiation alone, surgery + radiation, and surgery + radiation + chemotherapy. Lung metastasis is a prognostic factor of extremely poor outcomes. We conclude that patients with glioblastoma extracranial metastasis have poor prognosis, but there has been a progressive lengthening of survival in each successive decade from 1940 to 2000.

There is not a clinically available technique for measuring the physiological traits causing obstructive sleep apnea (OSA). Therefore, it is often difficult to determine why an individual has OSA or to what extent the various traits contribute to the development of OSA. In this study, we present a noninvasive method for measuring four important physiological traits causing OSA: 1) pharyngeal anatomy/collapsibility, 2) ventilatory control system gain (loop gain), 3) the ability of the upper airway to dilate/stiffen in response to an increase in ventilatory drive, and 4) arousal threshold. These variables are measured using a single maneuver in which continuous positive airway pressure (CPAP) is dropped from an optimum to various suboptimum pressures for 3- to 5-min intervals during sleep. Each individual's set of traits is entered into a physiological model of OSA that graphically illustrates the relative importance of each trait in that individual. Results from 14 subjects (10 with OSA) are described. Repeatability measurements from separate nights are also presented for four subjects. The measurements and model illustrate the multifactorial nature of OSA pathogenesis and how, in some individuals, small adjustments of one or another trait (which might be achievable with non-CPAP agents) could potentially treat OSA. This technique could conceivably be used clinically to define a patient's physiology and guide therapy based on the traits.

We compared the effect of oxygen on the apnea-hypopnea index (AHI) in six obstructive sleep apnea patients with a relatively high loop gain (LG) and six with a low LG. LG is a measure of ventilatory control stability. In the high LG group (unstable ventilatory control system), oxygen reduced the LG from 0.69+/-0.18 to 0.34+/-0.04 (p<0.001) and lowered the AHI by 53+/-33% (p=0.04 compared to the percent reduction in the low LG group). In the low LG group (stable ventilatory control system), oxygen had no effect on LG (0.24+/-0.04 on room air, 0.29+/-0.07 on oxygen, p=0.73) and very little effect on AHI (8+/-27% reduction with oxygen). These data suggest that ventilatory instability is an important mechanism causing obstructive sleep apnea in some patients (those with a relatively high LG), since lowering LG with oxygen in these patients significantly reduces AHI.

Introduction It is increasingly becoming accepted that inflammation may play an important role in the pathogenesis of Alzheimer’s disease (AD), as several immune-related genes have been associated with AD. Among these is tumor necrosis factor (TNF)-α, a proinflammatory cytokine known to play an important role in autoimmune disorders, including rheumatoid arthritis (RA). Although AD and RA appear to involve similar pathological mechanisms through the production of TNF-α, the relationship between AD and RA remains unknown. Objective To determine the relative risk of AD among RA patients and non-RA patients, and whether anti-TNF therapy for RA was associated with a lower risk of AD in RA patients. Methods We performed a nested case-control study of more than 8.5 million commercially insured adults (aged ≥18 years) in all 50 US states, Puerto Rico, and US Virgin Islands in the Verisk Health claims database. We derived a sub-cohort of subjects with a diagnosis of RA (controls), or RA and AD (cases), matching cases and controls based on age, sex, exposure assessment period, and methotrexate treatment. We also assessed relative risk of AD following exposure to standard RA therapies, including anti-TNF agents (infliximab, adalimumab, etanercept), methotrexate, prednisone, sulfasalazine, and rituximab. Odds ratios were adjusted for comorbidities, including coronary artery disease, diabetes mellitus, and peripheral vascular disease. Results AD was more prevalent (p < 0.0001) among RA patients (0.79 %) than among those without RA (0.11 %). Chronic conditions such as coronary artery disease (odds ratio [OR] 1.48; 95 % confidence interval [CI] 1.04–2.05; p = 0.03), diabetes (OR 1.86; 95 % CI 1.32–2.62; p = 0.0004), and peripheral vascular disease (OR 1.61; 95 % CI 1.06–2.43; p = 0.02) significantly increased the relative risk of AD among RA patients. Exposure to anti-TNF agents as a class, but not other immunosuppressive drugs studied, was associated with lowered risk of AD among RA patients (unadjusted OR 0.44; 95 % CI 0.22–0.87; p = 0.02; adjusted OR 0.45; 95 % CI 0.23–0.90; p = 0.02). Sub-group analysis demonstrated that of the three anti-TNF agents studied, only etanercept (unadjusted OR, 0.33; 95 % CI 0.08–0.94; p = 0.03; adjusted OR 0.30; 95 % CI 0.08–0.89; p = 0.02) was associated with a decreased risk of AD in RA patients. Conclusion There is an increased risk of AD in the studied RA population. The relative risk of AD among RA subjects was lowered in those exposed to etanercept. Anti-TNF therapy with etanercept shows promise as a potential treatment for AD.

Older age is associated with increased pharyngeal airway collapsibility during sleep independent of gender and BMI. These data may at least partially explain the mechanisms underlying the predisposition for pharyngeal collapse in the elderly.

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