Unexpectedly high prevalence of sarcoidosis in a representative U.S. Metropolitan population

SummaryThe prevalence of sarcoidosis in the United States is unknown, with estimates ranging widely from 1 to 40 per 100,000. We sought to determine the prevalence of sarcoidosis in our health system compared to other rare lung diseases and to further establish if the prevalence was changing over time. We interrogated the electronic medical records of all patients treated in our health system from 1995 to 2010 (1.48 million patients) using the common ICD9 codes for sarcoidosis (135), lung cancer (162), and several other lung diseases characterized, like sarcoidosis, as “rare lung diseases”. The patient demographic information (race, gender, age) was further analyzed to identify signature data patterns. The prevalence of sarcoidosis in our health system increased steadily from 164/100,000 in 1995 to 330/100,000 in 2010, and this trend could not be ascribed simply to changes in patient demographics or patient referral patterns. We further estimate that the prevalence of sarcoidosis exceeds 48 per 100,000 in Franklin County, Ohio, the demographic profile of which is nearly identical to that of the U.S. Sarcoidosis prevalence increased over time relative to lung cancer, a benchmark disease with stable disease prevalence, and exceeded that of other rare lung diseases. We postulate that the observed 2-fold increase in sarcoidosis disease prevalence in our health system is primarily related to improved detection and diagnostic approaches, and we conclude that the actual prevalence of sarcoidosis in central Ohio greatly exceeds current U.S. estimates

Sexual motivation is reflected by stimulus-dependent motor cortex excitability

Sexual behavior involves motivational processes. Findings from both animal models and neuroimaging in humans suggest that the recruitment of neural motor networks is an integral part of the sexual response. However, no study so far has directly linked sexual motivation to physiologically measurable changes in cerebral motor systems in humans. Using transcranial magnetic stimulation in hetero- and homosexual men, we here show that sexual motivation modulates cortical excitability. More specifically, our results demonstrate that visual sexual stimuli corresponding with one's sexual orientation, compared with non-corresponding visual sexual stimuli, increase the excitability of the motor cortex. The reflection of sexual motivation in motor cortex excitability provides evidence for motor preparation processes in sexual behavior in humans. Moreover, such interrelationship links theoretical models and previous neuroimaging findings of sexual behavio

Gannets are not attracted to fishing vessels in Iceland-potential influence of a discard ban and food availability

BLC was supported by a NERC GW4+ Doctoral Training Partnership studentship from the Natural Environment Research Council [NE/L002434/1]. We thank Ólafur Torfason, Niall Tierney, and Rachel Stroud for fieldwork assistance in Skrúður, and Mamma-Rósa for food and housing in Vestmannaeyjar. We thank the Hellisey hunting club for the use of cabin and assistance with boat trips to Hellisey. We thank Filipa Samarra, Miguel Neves, Gary Haskins, and team members in the Icelandic Orca Project for boat trips to Hellisey. We thank Lucy Hawkes, David Pascall, Alice Williams, Richard Phillips, Brendan Godley and all reviewers for constructive comments on the manuscript. The GPS tracking data are available through the BirdLife International Seabird Tracking Database (http://www.seabirdtracking.org).Peer reviewedPublisher PD

Circulating exosomal microRNA expression patterns distinguish cardiac sarcoidosis from myocardial ischemia.

OBJECTIVE: Cardiac sarcoidosis is difficult to diagnose, often requiring expensive and inconvenient advanced imaging techniques. Circulating exosomes contain genetic material, such as microRNA (miRNA), that are derived from diseased tissues and may serve as potential disease-specific biomarkers. We thus sought to determine whether circulating exosome-derived miRNA expression patterns would distinguish cardiac sarcoidosis (CS) from acute myocardial infarction (AMI). METHODS: Plasma and serum samples conforming to CS, AMI or disease-free controls were procured from the Biologic Specimen and Data Repository Information Coordinating Center repository and National Jewish Health. Next generation sequencing (NGS) was performed on exosome-derived total RNA (n = 10 for each group), and miRNA expression levels were compared after normalization using housekeeping miRNA. Quality assurance measures excluded poor quality RNA samples. Differentially expressed (DE) miRNA patterns, based upon \u3e2-fold change (p \u3c 0.01), were established in CS compared to controls, and in CS compared to AMI. Relative expression of several DE-miRNA were validated by qRT-PCR. RESULTS: Despite the advanced age of the stored samples (~5-30 years), the quality of the exosome-derived miRNA was intact in ~88% of samples. Comparing plasma exosomal miRNA in CS versus controls, NGS yielded 18 DE transcripts (12 up-regulated, 6 down-regulated), including miRNA previously implicated in mechanisms of myocardial injury (miR-92, miR-21) and immune responses (miR-618, miR-27a). NGS further yielded 52 DE miRNA in serum exosomes from CS versus AMI: 5 up-regulated in CS; 47 up-regulated in AMI, including transcripts previously detected in AMI patients (miR-1-1, miR-133a, miR-208b, miR-423, miR-499). Five miRNAs with increased DE in CS included two isoforms of miR-624 and miR-144, previously reported as markers of cardiomyopathy. CONCLUSIONS: MiRNA patterns of exosomes derived from CS and AMI patients are distinct, suggesting that circulating exosomal miRNA patterns could serve as disease biomarkers. Further studies are required to establish their specificity relative to other cardiac disorders

Inhibition of the mechano-enzymatic amyloidogenesis of transthyretin: role of ligand affinity, binding cooperativity and occupancy of the inner channel

Dissociation of the native transthyretin (TTR) tetramer is widely accepted as the critical step in TTR amyloid fibrillogenesis. It is modelled by exposure of the protein to non-physiological low pH in vitro and is inhibited by small molecule compounds, such as the drug tafamidis. We have recently identified a new mechano-enzymatic pathway of TTR fibrillogenesis in vitro, catalysed by selective proteolytic cleavage, which produces a high yield of genuine amyloid fibrils. This pathway is efficiently inhibited only by ligands that occupy both binding sites in TTR. Tolcapone, which is bound with similar high affinity in both TTR binding sites without the usual negative cooperativity, is therefore of interest. Here we show that TTR fibrillogenesis by the mechano-enzymatic pathway is indeed more potently inhibited by tolcapone than by tafamidis but neither, even in large molar excess, completely prevents amyloid fibril formation. In contrast, mds84, the prototype of our previously reported bivalent ligand TTR 'superstabiliser' family, is notably more potent than the monovalent ligands and we show here that this apparently reflects the critical additional interactions of its linker within the TTR central channel. Our findings have major implications for therapeutic approaches in TTR amyloidosis

The Vertical Structure and Ultraviolet Spectrum of Accretion Disks Heated by Internal Dissipation in Active Galactic Nuclei

We present an improved calculation of the vertical structure and ultraviolet spectrum of a dissipative accretion disk in an AGN. We calculate model spectra in which the viscous stress is proportional to the total pressure, the gas pressure only and the geometric mean of the radiation and gas pressures (cf. Laor & Netzer 1989: LN89). As a result of a more complete treatment of absorptive opacity, we find greater overall spectral curvature than did LN89, as well as larger amplitudes in both the Lyman and HeII photoionization edges. The local black body approximation is not a good description of the near UV spectrum. With relativistic corrections (appropriate to non-rotating black holes) included, we find that the near UV spectrum hardens with increasing m-dot / m_8 (m-dot is the accretion rate in Eddington units, m_8 the black hole mass in units of 10^8 M_Sun). The near UV spectrum is consistent with observations if m-dot/ m_8 \sim 10^{-3}, but disks this cold would have large, and unobserved, absorption features at the Lyman edge. The edge amplitude is reduced when m-dot/m_8 is larger, but then the near-UV slope is too hard to match observations. We conclude that models in which conventional disks orbit non-rotating black holes do not adequately explain UV continuum production in AGN.Comment: AAS LaTe