Background

The specificity of the aquaporin-4 antibody to predict recurrent inflammatory central nervous system disease has led to the design of the 2015 neuromyelitis optica spectrum disorder criteria which capture all aquaporin-4 antibody seropositive patients.

Objective

The purpose of this study was to compare treatment outcomes in aquaporin-4 antibody seropositive patients who met the previous 2006 clinical criteria for neuromyelitis optica with patients who meet the 2015 neuromyelitis optica spectrum disorder criteria.

Methods

The study involved a three-center retrospective chart review of clinical outcomes among aquaporin-4 patients diagnosed with neuromyelitis optica and neuromyelitis optica spectrum disorder.

Results

Hazard ratios of relapse during immunosuppressive therapy, relative to pre-therapy, were not significantly different for patients who met the 2006 criteria of neuromyelitis optica versus the 2015 neuromyelitis optica spectrum disorder criteria among those treated with azathioprine ( p = 0.24), mycophenolate mofetil ( p = 0.63), or rituximab ( p = 0.97).

Conclusion

Reductions in the hazard of relapse during treatment with immunosuppressive therapies, relative to average pre-treatment, were not different for aquaporin-4 antibody seropositive patients categorized using the 2006 criteria of neuromyelitis optica and the 2015 neuromyelitis optica spectrum disorder criteria. These therapeutic findings support the design of the 2015 neuromyelitis optica spectrum disorder criteria which capture all aquaporin-4 antibody seropositive patients.

OBJECTIVE - To describe trends of primary efficacy and safety outcomes of islet transplantation in type 1 diabetes recipients with severe hypoglycemia from the Collaborative Islet Transplant Registry (CITR) from 1999 to 2010. RESEARCH DESIGN AND METHODS -

Neuromyelitis optica (NMO) (and NMO spectrum disorder) is an autoimmune inflammatory disease of the CNS primarily affecting spinal cord and optic nerves. Reliable and sensitive biomarkers for onset, relapse, and progression in NMO are urgently needed becau

Black carbon (BC) was characterized by three complementary techniques - incandescence (single particle soot photometer, SP2, at Parque Morelos), light absorption (cavity ringdown spectrometer with integrating nephelometer, CRDS-Neph, at Parque Morelos and Aethalometers at seven locations), and volatility (volatility tandem differential mobility analyzer, V-TDMA) during the Cal-Mex 2010 campaign. SP2, CRDS-Neph, and Aethalometer measurements characterized the BC mass, and SP2 and V-TDMA measurements also quantified BC-containing particle number, from which mass-mean BC diameters were calculated. Onaverage, the mass concentrations measured in Tijuana (1.8±2.6μgm-3 at Parque Morelos and 2.6μgm-3 in other regions of Tijuana) were higher than in San Diego or the international border crossing (0.5±0.6μgm-3). The observed BC mass concentrations were attributable to nighttime urban burning activities and diesel vehicles, both from the local (Baja California) and transported (Southern California) diesel vehicle fleets. Comparisons of the SP2 and co-located Aethalometers indicated that the two methods measured similar variations in BC mass concentrations (correlation coefficients greater than 0.85), and the mass concentrations were similar for the BC particles identified from nighttime urban burning sources. When the BC source changed to diesel vehicle emissions, the SP2 mass concentrations were lower than the Aethalometer mass concentrations by about 50%, likely indicating a change in the mass absorption efficiency and quantification by the Aethalometers. At Parque Morelos there were up to three different-sized modes of BC mass in particles: one mode below 100nm, one near 100nm, and another between 200 and 300nm. The mode between 200 and 300nm was associated with urban burning activities that influenced the site during evening hours. When backtrajectories indicated that airmasses came from the south to the Parque Morelos site, BC mass in particles was also larger (mass median diameter of 170nm rather than 155nm), consistent with the higher fraction of older diesel vehicles in the Tijuana fleet compared to the vehicles found in southern California. © 2013 Elsevier Ltd.

The N-terminal region (NTR) of ryanodine receptor (RyR) channels is critical for the regulation of Ca²⁺ release during excitation-contraction (EC) coupling in muscle. The NTR hosts numerous mutations linked to skeletal (RyR1) and cardiac (RyR2) myopathies, highlighting its potential as a therapeutic target. Here, we constructed two biosensors by labeling the mouse RyR2 NTR at domains A, B, and C with FRET pairs. Using fluorescence lifetime (FLT) detection of intramolecular FRET signal, we developed high-throughput screening (HTS) assays with these biosensors to identify small-molecule RyR modulators. We then screened a small validation library and identified several hits. Hits with saturable FRET dose-response profiles and previously unreported effects on RyR were further tested using [³H]ryanodine binding to isolated sarcoplasmic reticulum vesicles to determine effects on intact RyR opening in its natural membrane. We identified three novel inhibitors of both RyR1 and RyR2 and two RyR1-selective inhibitors effective at nanomolar Ca²⁺. Two of these hits activated RyR1 only at micromolar Ca²⁺, highlighting them as potential enhancers of excitation-contraction coupling. To determine whether such hits can inhibit RyR leak in muscle, we further focused on one, an FDA-approved natural antibiotic, fusidic acid (FA). In skinned skeletal myofibers and permeabilized cardiomyocytes, FA inhibited RyR leak with no detrimental effect on skeletal myofiber excitation-contraction coupling. However, in intact cardiomyocytes, FA induced arrhythmogenic Ca²⁺ transients, a cautionary observation for a compound with an otherwise solid safety record. These results indicate that HTS campaigns using the NTR biosensor can identify compounds with therapeutic potential.

Rationale

Following acute respiratory distress syndrome (ARDS), joblessness is common but poorly understood.

Objectives

To evaluate the timing of return to work after ARDS, and associated risk factors, lost earnings, and changes in healthcare coverage Methods: Over 12-month longitudinal follow-up, ARDS survivors from 43 U.S. ARDSNet hospitals provided employment and healthcare coverage data via structured telephone interviews. Factors associated with the timing of return to work were assessed using Fine and Gray regression analysis. Lost earnings were estimated using Bureau of Labor Statistics data.

Measurements and main results

Of 922 consenting survivors, 386 (42%) were employed before ARDS (56% male; mean ± SD age, 45 ± 13 yr), with seven dying by 12-month follow-up. Of 379 previously employed 12-month survivors, 166 (44%) were jobless at 12-month follow-up. Accounting for competing risks of death and retirement, half of enrolled and previously employed survivors returned to work by 13 weeks after hospital discharge, with 68% ever returning by 12 months. Delays in return to work were associated with longer hospitalization and older age among nonwhite survivors. Over 12-month follow-up, 274 (71%) survivors accrued lost earnings, averaging $26,949 ± $22,447 (60% of pre-ARDS annual earnings). Jobless survivors experienced a 14% (95% confidence interval, 5-22%; P = 0.002) absolute decrease in private health insurance (from 44% pre-ARDS) and a 16% (95% confidence interval, 7-24%; P < 0.001) absolute increase in Medicare and Medicaid (from 33%).

Conclusions

At 12 months after ARDS, nearly one-half of previously employed survivors were jobless. Post-ARDS joblessness is associated with readily identifiable patient and hospital variables and accompanied by substantial lost earnings and a shift toward government-funded healthcare coverage.