The Ro autoantigen is a ring-shaped RNA-binding protein that binds misfolded RNAs in nuclei and is proposed to function in quality control. In the cytoplasm, Ro binds noncoding RNAs, called Y RNAs, that inhibit access of Ro to other RNAs. Ro also assists survival of mammalian cells and at least one bacterium after UV irradiation. In mammals, Ro undergoes dramatic localization changes after UV irradiation, changing from mostly cytoplasmic to predominantly nuclear. Here, we report that a second role of Y RNAs is to regulate the subcellular distribution of Ro. A mutant Ro protein that does not bind Y RNAs accumulates in nuclei. Ro also localizes to nuclei when Y RNAs are depleted. By assaying chimeric proteins in which portions of mouse Ro were replaced with bacterial Ro sequences, we show that nuclear accumulation of Ro after irradiation requires sequences that overlap the Y RNA binding site. Ro also accumulates in nuclei after oxidative stress, and similar sequences are required. Together, these data reveal that Ro contains a signal for nuclear accumulation that is masked by a bound Y RNA and suggest that Y RNA binding may be modulated during cell stress.
Background The impact of palmoplantar psoriasis on health-related quality of life (QoL) is largely unknown. Objective To compare clinical characteristics and patient-reported outcomes between patients with palmoplantar psoriasis and moderate-to-severe plaque psoriasis. Methods We conducted a cross-sectional study of patients with plaque psoriasis (N=1,153) and palmoplantar psoriasis (N=66) currently receiving systemic or light treatment for psoriasis. Results Patients with palmoplantar psoriasis were more likely to report Dermatology Life Quality Index scores that correspond to at least a moderate impact on QoL (odds ratio [OR] 2.08; 95% confidence interval [CI], 1.20-3.61); problems with mobility (OR 1.98; 95% CI, 1.10-3.58), self-care (OR 3.12; 95% CI, 1.24-7.86), and usual activities (OR 2.47; 95% CI, 1.44-4.22) on the European Quality of Life-5 Dimensions questionnaire; and heavy topical prescription use of at least twice daily in the preceding week (OR 2.81; 95% CI, 1.63-4.85) than those with plaque psoriasis. Limitations Our assessment tools may not account for all dimensions of health-related QoL affected by palmoplantar disease, and these results may not be generalizable to patients with milder forms of psoriasis. Conclusion Patients with palmoplantar psoriasis suffer from greater health-related QoL impairment and are more likely to report heavy use of topical prescriptions than those with moderate-to-severe plaque psoriasis.
Nontuberculous mycobacteria (NTM) are a diverse group of organisms that are ubiquitous in the environment, and the incidence of cutaneous infections due to NTM has been steadily increasing. Cutaneous infections due to NTM can be difficult to diagnose, due to their wide spectrum of clinical presentations and histopathological findings that are often nonspecific. A variety of modalities including tissue culture and polymerase chain reaction (PCR) assays may be necessary to identify the organism. Treatment can also be challenging, as it can depend on multiple factors, including the causative organism, the patient's immunological status, and the extent of disease involvement. In this review, we discuss the common presentations of cutaneous NTM infections, diagnostic tools, and treatment recommendations. A multi-disciplinary approach that involves good communication between the clinician, the histopathologist, the microbiologist, and infectious disease specialists can help lead to successful diagnosis and management.
Background The prevalence of infections due to nontuberculous mycobacteria (NTM) is increasing worldwide, yet little is known about the epidemiology and pathophysiology of these ubiquitous environmental organisms. Pulmonary disease due to Mycobacterium avium complex is most prevalent, but many other NTM species can cause disease in virtually any organ system. As NTM becomes an increasingly common cause of morbidity and mortality, more information is needed about the epidemiology of NTM disease. Methods We conducted a retrospective chart review of all patients with cultures that grew NTM at a Midwestern tertiary hospital from 1996 to 2017. Information on demographics, medical history, clinical findings, treatment, and outcome was obtained from medical records of all NTM isolates. American Thoracic Society/Infectious Diseases Society of America criteria were used to define pulmonary NTM infections. Results We identified 1064 NTM isolates, 365 of which met criteria for NTM infection. Pulmonary cases predominated (185 of 365; 50.7%), followed by skin/soft tissue (56 of 365; 15.3%), disseminated (40 of 365; 11%), and lymphatic (28 of 365; 7.7%) disease. Mycobacterium avium complex was the most common species (184 of 365; 50.4%). Individuals aged >50 years were most affected (207 of 365; 56.7%). Common comorbidities included structural lung disease (116 of 365; 31.8%), use of immunosuppressive medications (78 of 365; 21.4%), malignancy (59 of 365; 16.2%), and human immunodeficiency virus (42 of 365; 11.5%). Conclusions This large cohort provides information on the demographics, risk factors, and disease course of patients with pulmonary and extrapulmonary NTM infections. Most patients had medical comorbidities that resulted in anatomic, genetic, or immunologic risk factors for NTM infection. Further population-based studies and increased disease surveillance are warranted to further characterize NTM infection prevalence and trends.
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