Publications

Double-stranded DNA (dsDNA) viral infections constitute a major complication following solid organ and stem cell transplantation. Few therapeutic options are currently available for the treatment of such infections in highly immunocompromised hosts. Brincidofovir is an oral investigational drug with broad antiviral activity against dsDNA viruses in vitro, but clinical experience is limited. Here we report a young female who developed a mixed infection with adenovirus, cytomegalovirus, Epstein-Barr virus and BK polyomavirus after an allogeneic stem cell transplant, and was successfully treated with brincidofovir.

Following the advent of molecular assays that measure T cell receptor excision circles (TRECs) present in recent thymic emigrants, it has been conclusively shown that thymopoiesis persists in most adults, but that functional output decreases with age, influencing the maintenance of a diverse and functional T cell receptor (TCR) repertoire. Space flight has been shown to result in a variety of phenotypic and functional changes in human T cells and in the reactivation of latent viruses. While space flight has been shown to influence thymic architecture in rodents, thymopoiesis has not previously been assessed in astronauts. Here, we assessed thymopoiesis longitudinally over a 1-year period prior to and after long-term space flight (median duration, 184 days) in 16 astronauts. While preflight assessments of thymopoiesis remained quite stable in individual astronauts, we detected significant suppression of thymopoiesis in all subjects upon return from space flight. We also found significant increases in urine and plasma levels of endogenous glucocorticoids coincident with the suppression of thymopoiesis. The glucocorticoid induction and thymopoiesis suppression were transient, and they normalized shortly after return to Earth. This is the first report to our knowledge to prospectively demonstrate a significant change in thymopoiesis in healthy individuals in association with a defined physiologic emotional and physical stress event. These results suggest that suppression of thymopoiesis has the potential to influence the maintenance of the TCR repertoire during extended space travel. Further studies of thymopoiesis and endogenous glucocorticoids in other stress states, including illness, are warranted.

OBJECTIVE

We investigated the association between 52 risk variants identified through genome-wide association studies and disease severity in multiple sclerosis (MS).

METHODS

Ten unique MS case data sets were analyzed. The Multiple Sclerosis Severity Score (MSSS) was calculated using the Expanded Disability Status Scale at study entry and disease duration. MSSS was considered as a continuous variable and as 2 dichotomous variables (median and extreme ends; MSSS of ≤5 vs >5 and MSSS of <2.5 vs ≥7.5, respectively). Single nucleotide polymorphisms (SNPs) were examined individually and as both combined weighted genetic risk score (wGRS) and unweighted genetic risk score (GRS) for association with disease severity. Random-effects meta-analyses were conducted and adjusted for cohort, sex, age at onset, and HLA-DRB1*15:01.

RESULTS

A total of 7,125 MS cases were analyzed. The wGRS and GRS were not strongly associated with disease severity after accounting for cohort, sex, age at onset, and HLA-DRB1*15:01. After restricting analyses to cases with disease duration ≥10 years, associations were null (p value ≥0.05). No SNP was associated with disease severity after adjusting for multiple testing.

CONCLUSIONS

The largest meta-analysis of established MS genetic risk variants and disease severity, to date, was performed. Results suggest that the investigated MS genetic risk variants are not associated with MSSS, even after controlling for potential confounders. Further research in large cohorts is needed to identify genetic determinants of disease severity using sensitive clinical and MRI measures, which are critical to understanding disease mechanisms and guiding development of effective treatments.

INTRODUCTION

The purpose of the study was to describe changes in smoking intensity among US Latinos and non-Latinos from 1997 to 2014.

METHODS

National Health Interview Survey data between 1997 and 2014 were used to determine the number of cigarettes smoked per day (CPD) among Latino and non-Latino adults who had smoked at least 100 cigarettes in their lifetime and were currently smoking every day or some days (ie, current smokers).

RESULTS

CPD declined steadily throughout the observation period and were consistently lower for Latino than for non-Latino smokers. However, decreases were not equal across birth cohorts, genders, or among Latino national background groups. CPD declined most among Mexican men and least among younger generations, Cuban women, and acculturated Latina women. Additionally, declines in smoking intensity seemed to slow over time among low CPD consumers.

CONCLUSIONS

Although smoking intensity has decreased substantially since the late 1990s, CPD data suggest that declines are slowing among younger generations and certain Latina women. Effective tobacco control strategies should be developed to discourage even very light and nondaily smoking.

IMPLICATIONS

Few studies have been conducted on how smoking intensity has changed since the late 1990s. Between 2004 and 2011, when the decline in smoking prevalence slowed, it is unknown how smoking intensity (ie, CPD) changed by age. Additionally, no research has assessed differences and changes in smoking intensity over time among Latinos. From this study we learned that smoking intensity declined significantly since the late 1990s, but this decline slowed among younger generations of smokers and certain Latina women. Findings suggest that future patterns of smoking intensity may only marginally decline in the near future.