The microbiome can promote or disrupt human health by influencing both adaptive and innate immune functions. We tested whether bacteria that normally reside on human skin participate in host defense by killing Staphylococcus aureus, a pathogen commonly found in patients with atopic dermatitis (AD) and an important factor that exacerbates this disease. High-throughput screening for antimicrobial activity against S.aureus was performed on isolates of coagulase-negative Staphylococcus (CoNS) collected from the skin of healthy and AD subjects. CoNS strains with antimicrobial activity were common on the normal population but rare on AD subjects. A low frequency of strains with antimicrobial activity correlated with colonization by S.aureus. The antimicrobial activity was identified as previously unknown antimicrobial peptides (AMPs) produced by CoNS species including Staphylococcus epidermidis and Staphylococcus hominis. These AMPs were strain-specific, highly potent, selectively killed S.aureus, and synergized with the human AMP LL-37. Application of these CoNS strains to mice confirmed their defense function in vivo relative to application of nonactive strains. Strikingly, reintroduction of antimicrobial CoNS strains to human subjects with AD decreased colonization by S.aureus. These findings show how commensal skin bacteria protect against pathogens and demonstrate how dysbiosis of the skin microbiome can lead to disease.
• Children with SCA and stroke show severe parenchymal and vascular abnormalities that can be assessed using a vasculopathy grading scale. • Results from the SWiTCHTrial support concerns about ineffectiveness of transfusion therapy in preventing cerebrovascular injury progression.The Stroke With Transfusions Changing to Hydroxyurea (SWiTCH) trial compared standard (transfusions/chelation) to alternative (hydroxyurea/phlebotomy) treatment to prevent recurrent stroke and manage iron overload in children chronically transfused over 7 years before enrollment. Standardized brain magnetic resonance imaging/magnetic resonance angiography (MRA) and transcranial Doppler (TCD) exams were performed at entry and exit, with a central blinded review. A novel MRA vasculopathy grading scale demonstrated frequent severe baseline left/right vessel stenosis (53%/41% ‡Grade 4); 31% had no vessel stenosis on either side. Baseline parenchymal injury was prevalent (85%/79% subcortical, 53%/37% cortical, 50%/35% subcortical and cortical). Most children had low or uninterpretable baseline middle cerebral artery TCD velocities, which were associated with worse stenoses (incidence risk ratio [IRR] 5 5.1, P £ .0001 and IRR 5 4.1, P < .0001) than normal velocities; only 2% to 12% had any conditional/abnormal velocity. Patients with adjudicated stroke (7) and transient ischemic attacks (19 in 11 standard/8 alternative arm subjects) had substantial parenchymal injury/vessel stenosis. At exit, 1 child (alternative arm) had a new silent infarct, and another had worse stenosis. SWiTCH neuroimaging data document severe parenchymal and vascular abnormalities in children with SCA and stroke and support concerns about chronic transfusions lacking effectiveness for preventing progressive cerebrovascular injury. The novel SWiTCH vasculopathy grading scale warrants validation testing and consideration for use in future clinical trials. This trial was registered at www.clinicaltrials.gov as #NCT00122980. (Blood. 2014;124(6):891-898)
A systematic review of the literature was conducted to determine the estimates of and definitions for human papillomavirus (HPV) persistence in women following treatment of cervical intra-epithelial neoplasia (CIN). A total of 45 studies presented data on post-treatment HPV persistence among 6,106 women. Most studies assessed HPV persistence after loop excision (42%), followed by conization (7%), cryotherapy (11%), laser treatment (4%), interferon-alpha, therapeutic vaccination, and photodynamic therapy (2% each) and mixed treatment (38%). Baseline HPV testing was conducted before or at treatment for most studies (96%). Follow-up HPV testing ranged from 1.5 to 80 months after baseline. Median HPV persistence tended to decrease with increasing follow-up time, declining from 27% at 3 months after treatment to 21% at 6 months, 15% at 12 months, and 10% at 24 months. Post-treatment HPV persistence estimates varied widely and were influenced by patient age, HPV-type, detection method, treatment method, and minimum HPV post-treatment testing interval. Loop excision and conization appeared to outperform cryotherapy procedures in terms of their ability to clear HPV infection. This systematic review provides evidence for the substantial heterogeneity in post-treatment HPV DNA testing practices and persistence estimates.
Self-collected specimen screening results showed strong agreement to clinical-collected specimens, except for MG, which was consistently detected more commonly in self-collected than in physician-collected specimens. Acceptability of the self-collection procedure was high at baseline and increased modestly over time. In high-risk, low-resource settings, STI screening with self-collected specimens provides a reliable and acceptable alternative to screening with physician-collected specimens.
Pharmacies have been endorsed as alternative vaccine delivery sites to improve vaccination rates through increased access to services. Our objective was to identify challenges and facilitators to adolescent and adult vaccination provision in pharmacy settings in the United States. We recruited 40 licensed pharmacists in states with different pharmacy vaccination laws. Eligible pharmacists previously administered or were currently administering human papillomavirus (HPV); tetanus, diphtheria, and pertussis (TDAP); or meningitis (meningococcal conjugate vaccine [MCV4]) vaccines to adolescents aged 9 to 17 years. Pharmacists participated in a semistructured survey on in-pharmacy vaccine provision. Pharmacists commonly administered vaccinations to age-eligible adolescents and adults: influenza (100%, 100%), pneumococcal (35%, 98%), TDAP (80%, 98%), MCV4 (60%, 78%), and HPV (45%, 53%). Common challenges included reimbursement/insurance coverage (28%, 78%), education of patients/parents (30%, 40%), and pharmacists’ time constraints (28%, 35%). Three-quarters of pharmacists reported that vaccination rates could be increased. National efforts should expand insurance coverage for vaccine administration reimbursement and improve data information systems to optimize provision within pharmacies.
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