The ability of the human bacterial pathogen Neisseria meningitidis to cause invasive disease depends on survival in the bloodstream via mechanisms to suppress complement activation. In this study, we show that prophage genes coding for T and B cell stimulating protein B (TspB), which is an immunoglobulin-binding protein, are essential for survival of N. meningitidis group B strain H44/76 in normal human serum (NHS). H44/76 carries three genes coding for TspB. Mutants having all tspB genes inactivated did not survive in >5% NHS or IgG-depleted NHS. TspB appeared to inhibit IgM-mediated activation of the classical complement pathway, since survival of the tspB triple knockout was the same as that of the parent strain or a complemented mutant when the classical pathway was inactivated by depleting NHS of C1q and was increased in IgM-depleted NHS. A mutant solely carrying tspB gene nmbh4476_0681 was as resistant as the parent strain, while mutants carrying only nmbh4476_0598 or nmbh4476_1698 were killed in >5% NHS. The phenotype associated with TspB is formation of a matrix containing TspB, IgG, and DNA that envelopes aggregates of bacteria. Recombinant proteins corresponding to particular subdomains of TspB were found to have human IgG Fc␥-and/or DNA-binding activity, but only TspB derivatives containing both domains formed large, biofilm-like aggregates when combined with purified IgG and DNA. Recognizing the role of TspB in serum resistance may lead to a better understanding of why strains that carry tspB genes are associated with invasive meningococcal disease. Invasive Neisseria meningitidis is a major cause of bacterial meningitis and sepsis worldwide. The reasons for why some N. meningitidis strains cause disease and others do not are not well understood. With the exception of periodic epidemics occurring mainly in sub-Saharan Africa, disease caused by pathogenic N. meningitidis is relatively rare. However, asymptomatic carriage is comparatively common, ranging from ϳ5% to Ͼ80% depending on the population studied (1, 2). Host factors associated with increased risk of disease include complement deficiencies, carriage state, genetics, social behavior, and geographic location (reviewed in reference 3). Strains causing invasive disease, on the other hand, appear to be limited to those from a few, so-called hypervirulent lineages (2). However, not many specific characteristics of N. meningitidis strains have been identified that can be linked directly to disease. In an epidemiological study comparing disease-causing isolates with carriage isolates by microarray analysis during an outbreak of meningococcal disease in the Czech Republic, Bille et al. found a statistically significant association of the presence of prophage DNA with isolates that caused disease (4). However, the reasons for the link between the prophage DNA and invasive disease were not determined. Recently, we showed that the prophage gene ORF6 codes for an IgG-binding protein specific for the Fc portion of a human IgG2 paraprotein (5). The protein,...
Oral and topical zinc have been used for the treatment of acne, but there is a lack of definitive evidence for their efficacy. (a) To determine if mean serum zinc levels differ between acne patients and controls and (b) to determine the efficacy of zinc preparations in the treatment of acne. A systematic review and meta-analysis was performed according to recommended PRISMA [Preferred Reporting Items for Systematic Reviews and Meta-Analyses] guidelines. Subjects with acne had significantly lower serum zinc levels compared to controls. Patients who were treated with zinc had a significant improvement in mean inflammatory papule count compared to those who were not treated with zinc. There was no significant difference in the incidence of side effects in zinc supplementation vs comparators. Acne patients have decreased serum zinc levels. Zinc is effective for the treatment of acne, particularly at decreasing the number of inflammatory papules, when used as monotherapy or as an adjunctive treatment.
Background Mycosis fungoides (MF) is a cutaneous lymphoma; most patients present with early, skin-limited disease and are managed by dermatologists. Objective The purpose of this study was to systematically review and assess the evidence on topical treatments for early-stage (IA, IB, IIA) MF. Methods We performed a literature search via MEDLINE, Embase, Web of Science, and Cochrane databases. Grading Recommendations Assessment, Development and Evaluation (GRADE) criteria were used to assess the certainty of the data. Results Two searches yielded 1252 references; 26 met the inclusion criteria and included literature on nitrogen mustard, retinoids, corticosteroids, carmustine, fluorouracil, methotrexate-laurocapram, hexadecylphosphocholine, peldesine, ingenol mebutate, topical methotrexate with oxygen flow-assisted LP3 carrier, and resiquimod. Most studies were single intervention, observational series. Nitrogen mustard, with the most published reports, was effective with 12%-82% early-stage MF patients (total n > 1000) achieving complete remission (CR) (low certainty evidence). Clinical CR was achieved among 10%-60% treated with topical retinoids (low certainty evidence). Two moderate-sized retrospective case series on topical steroids had 18%-63% CR (low certainty evidence). Only single studies were available for the other therapies. Conclusions For most outcomes of interest, the GRADE certainty for topical therapies for early-stage MF was low. Further randomized controlled trials and inclusion of quality of life indicators are needed.
Objectives: With an ever-expanding medical knowledge base and requirements for clinical training, medical schools struggle to incorporate subspecialty education, such as otolaryngology (OTO), into curricula. This study aims to assess the current state of OTO education, and evaluate factors contributing to the extent of OTO teaching in United States (U.S.) medical schools. Methods: A 48-question survey evaluated the extent and practices of OTO teaching. The survey was distributed by email to all 155 LCME accredited U.S. allopathic medical schools in 2020 and 2021. Results: Sixty-eight unique responses were received (43.9% of U.S. allopathic medical schools). 36.8% (n = 25) of schools reported having formal expectations of OTO knowledge in their core curriculum. Only 1 school (1.5%) had a required OTO rotation; the majority of schools offered an optional third or fourth year clerkship rotation (76.5% and 95.6%, respectively). Schools with residency programs and who employ their faculty through an OTO or surgery department were more likely to have otolaryngologists teach basic science lectures and the Head & Neck exam, offer an optional third year rotation, and have formal expectations of rotating students. Conclusions: Medical schools with residency programs and who employ their faculty through an OTO or surgery department have more robust OTO curricula. Despite the ubiquity of OTO presentations across specialties, incorporation of OTO knowledge in U.S. medical school curricula remains variable, and at times limited.
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