Recognition of cytosolic DNA activates an IRF3-dependent innate immune response

Nucleic acid recognition upon viral infection triggers type I interferon production. Viral RNA is detected by both endosomal, TLR-dependent and cytosolic, RIG-I/MDA5-dependent pathways. TLR9 is the only known sensor of foreign DNA; it is unknown whether innate immune recognition of DNA exists in the cytosol. Here we present evidence that cytosolic DNA activates a potent type I interferon response to the invasive bacterium Listeria monocytogenes. The noninvasive Legionella pneumophila triggers an identical response through its type IV secretion system. Activation of type I interferons by cytosolic DNA is TLR independent and requires IRF3 but occurs without detectable activation of NF-kappaB and MAP kinases. Microarray analyses reveal a unique but overlapping gene-expression program activated by cytosolic DNA compared to TLR9- and RIG-I/MDA5-dependent responses. These findings define an innate immune response to DNA linked to type I interferon production.     

Young Female Donors Do Not Increase the Risk of Graft-versus-Host Disease or Impact Overall Outcomes in Pediatric HLA-Matched Sibling Hematopoietic Stem Cell Transplantation

Optimal donor selection is critical in hematopoietic stem cell transplantation (HSCT). Donor–recipient sex mismatch, donor age, and female donor–donor parity are known to impact graft-versus-host disease (GVHD) and outcomes in adults. Minor histocompatibility antigens encoded by the human Y chromosome can result in specific antibody formation in some female donors, may increase in frequency with increasing donor age, and may be contributory to the increased incidence of GVHD. To better understand the role of donor age/sex and sex matching in HSCT outcomes, we conducted a retrospective study of pediatric patients receiving their first myeloablative sibling donor HSCT (n?=?244) from 1998 to 2012. Observed rates of GVHD were low: 17% of patients surviving past engraftment (n?=?243) developed grades II to IV acute GVHD (aGVHD) and 14% surviving ≥ 100 days (n?=?229) developed chronic GVHD (cGVHD). On multivariate analysis the risk of aGVHD, cGVHD, and death increased with patient age as expected. Female donor sex and sex mismatch (female donor–male recipient) had no impact on the development of aGVHD. cGVHD was increased with female donors only if the donor was ≥12 years old. No cGVHD was observed among 109 patients aged < 10 years who received a 6/6 HLA-matched marrow HSCT, regardless of donor age or sex. Survival was mostly driven by diagnosis. Results suggest that in pediatric HSCT, young HLA-matched siblings are equivalently good donors regardless of sex or donor–recipient sex mismatch.     

Aspirin use and the prevention of acute ischemic cranial nerve palsy

PURPOSE: To assess the relationship of aspirin use and ischemic cranial nerve palsies among patients with diabetes mellitus and hypertension. METHODS: This retrospective case-control study involved 100 patients with ischemic cranial nerve palsies in association with diabetes, hypertension, or both (palsy cases) and 163 age-matched and sex-matched patients with diabetes, hypertension, or both but without ischemic cranial nerve palsies (nonpalsy control subjects). Comparisons were made with respect to duration of diabetes, dose and duration of aspirin use, dose and duration of tobacco use, and presence of cardiac or cerebrovascular disease. RESULTS: There were 20 oculomotor, 33 trochlear, 37 abducens, and 10 facial nerve palsy cases. The median duration of diabetes was 6 years for cases and 7 years for control subjects. There were 34 cases (34%) who had used aspirin for a mean duration of 5.5 years before the onset of the cranial nerve palsy and 49 control subjects (30.1%) who had used aspirin for a mean duration of 4.3 years. There were no significant differences between cases and control subjects for duration of diabetes (P =.94); aspirin use (P =.51), duration (P =.50), and dosage (P =.89); tobacco use (P =.73) and consumption (P =.45); and proportion of cardiac disease (P =.17). Cerebrovascular disease was significantly less common among palsy cases than nonpalsy control subjects (P<.001). There was no significant difference in the odds of a patient having cranial nerve palsy in the aspirin group compared with the nonaspirin group (odds ratio, 1.12; 95% confidence interval, 0.70-2.04). CONCLUSION: Aspirin use was not associated with a reduced rate of ischemic third, fourth, sixth, and seventh nerve palsies among patients with diabetes mellitus and hypertension. Aspirin appears to be ineffective in preventing ischemic third, fourth, sixth, and seventh cranial nerve palsies. Patients with ischemic cranial nerve palsy have a significantly lower rate of strokes and transient ischemic attacks than patients who have diabetes or hypertension but who do not have a history of cranial nerve palsy.     

Serum FSH and LH in male mice following aggressive and nonaggressive interaction

Previously isolated, adult, male mice were maintained for four days either in continued isolation or as pairs which were either separated from each other or not by a wire mesh barrier. Males without the barrier in place were categorized as dominant or subordinate on the basis of wounding. In general, fighting resulted in decreased concentrations of circulating FSH and LH, as well as the expected increase in adrenal weight and decrease in weight of the seminal vesicles. Such changes were decidedly more exaggerated in subordinates than among dominant males. Body weight was not affected by any of the experimental treatments. Pituitary content of the gonadotropins also remained relatively unchanged except for a significant depression in LH among dominant males.     

Quantifying clinical narrative redundancy in an electronic health record

Objective

Although electronic notes have advantages compared to handwritten notes, they take longer to write and promote information redundancy in electronic health records (EHRs). We sought to quantify redundancy in clinical documentation by studying collections of physician notes in an EHR.

Design and methods

We implemented a retrospective design to gather all electronic admission, progress, resident signout and discharge summary notes written during 100 randomly selected patient admissions within a 6 month period. We modified and applied a Levenshtein edit-distance algorithm to align and compare the documents written for each of the 100 admissions. We then identified and measured the amount of text duplicated from previous notes. Finally, we manually reviewed the content that was conserved between note types in a subsample of notes.

Measurements

We measured the amount of new information in a document, which was calculated as the number of words that did not match with previous documents divided by the length, in words, of the document. Results are reported as the percentage of information in a document that had been duplicated from previously written documents.

Results

Signout and progress notes proved to be particularly redundant, with an average of 78% and 54% information duplicated from previous documents respectively. There was also significant information duplication between document types (eg, from an admission note to a progress note).

Conclusion

The study established the feasibility of exploring redundancy in the narrative record with a known sequence alignment algorithm used frequently in the field of bioinformatics. The findings provide a foundation for studying the usefulness and risks of redundancy in the EHR.