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Competing Interests: Potential conflicts of interest . The authors: No reported conflicts of interest. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed.

Introduction: Ocular syphilis is a rare but potentially sight-threatening manifestation of infection with the spirochete Treponema pallidum subspecies pallidum . Molecular strain typing of clinical specimens obtained from patients with syphilis can provide useful epidemiological and clinical information. In this study, we assess the utility of non-ocular clinical samples in strain typing for patients with diagnosed ocular syphilis., Methods: We collected samples of excess blood, serum, and cerebrospinal fluid (CSF) from 6 patients with ocular syphilis treated in 2013-2016. DNA was extracted, purified, and then analyzed using an enhanced molecular typing method including sequence analysis of tp0548 , number of repeats in the arp gene, and restriction fragment length polymorphism of the tpr gene., Results: Molecular strain typing based on tp0548 gene sequence analysis revealed two cases of type F and two cases of type G in 3 of 6 (50%) cases with CSF samples, 1 of which was obtained after starting antibiotics. In a patient with 2 distinct episodes, the same tp0548 type (type G) was identified in both episodes using different sample types (CSF, whole blood). Serum samples were available in 6 cases, but none were successfully typed with any of the methods. Amplification of the tpr and arp genes was unsuccessful in all cases. Overall, strain types were identified in 4 of the 7 episodes., Conclusion: Treponema pallidum strain types F and G were detected in CSF or whole blood in 4 of 7 episodes in this series. We demonstrate moderate sensitivity of strain typing in ocular syphilis using non-ocular clinical specimens.

Cohesin is key to eukaryotic genome organization and acts throughout the cell cycle in an ATP-dependent manner. The mechanisms underlying cohesin ATPase activity are poorly understood. Here, we characterize distinct steps of the human cohesin ATPase cycle and show that the SMC1A and SMC3 ATPase domains undergo specific but concerted structural rearrangements along this cycle. Specifically, whereas the proximal coiled coil of the SMC1A ATPase domain remains conformationally stable, that of the SMC3 displays an intrinsic flexibility. The ATP-dependent formation of the heterodimeric SMC1A/SMC3 ATPase module (engaged state) favors this flexibility, which is counteracted by NIPBL and DNA binding (clamped state). Opening of the SMC3/RAD21 interface (open-engaged state) stiffens the SMC3 proximal coiled coil, thus constricting together with that of SMC1A the ATPase module DNA-binding chamber. The plasticity of the ATP-dependent interface between the SMC1A and SMC3 ATPase domains enables these structural rearrangements while keeping the ATP gate shut. VIDEO ABSTRACT., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Screening for syphilis increasingly relies on positive treponemal rather than nontreponemal tests (rapid plasma reagin [RPR]). We compared ocular syphilis in patients with nonreactive versus positive RPR., Methods: We conducted a retrospective observational cohort study of ocular syphilis treated at two New England hospitals 1996-2021 based on ophthalmologist-diagnosed eye findings and positive treponemal serology, regardless of RPR. We excluded patients with alternative diagnoses. We categorized RPR into nonreactive RPR, low-titer RPR (<1:8), and high-titer RPR (≥1:8) and compared early and long-term response to therapy., Results: Our sample included 115 patients with ocular syphilis (median follow-up 2.5 years): 25 (22%) nonreactive RPR, 21 (18%) low-titer RPR, 69 (60%) high-titer RPR. Compared with nonreactive and low-titer RPR, people with high-titer RPR were younger (mean 47 years, p<0.001), more likely male (93%, p<0.001) and more likely to be living with HIV (49%, p<0.001). People with nonreactive and low-titer RPR were less likely than high-titer RPR to have posterior/panuveitis (32% and 29% versus 75%, p<0.001) or abnormal CSF (26% and 35% versus 75%, p<0.001), and more likely to present with chronic eye findings (20% and 29% versus 1%, p<0.001). In long-term follow up, eye findings improved and did not recur in most patients (62% nonreactive, 68% low-titer, 96% high-titer RPR); improved but recurred in 29%, 11%, and 4%, respectively; and were stable in 10%, 21%, and 0%, respectively., Conclusion: Patients with ocular syphilis and nonreactive RPR are similar to patients with low-titer RPR, and antibiotic therapy is beneficial in most., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Objective: To offer pragmatic, evidence-informed advice on administering corticosteroids in otolaryngology during the coronavirus disease 2019 (COVID-19) pandemic, considering therapeutic efficacy, potential adverse effects, susceptibility to COVID-19, and potential effects on efficacy of vaccination against SARS-CoV-2, which causes COVID-19., Data Sources: PubMed, Cochrane Library, EMBASE, CINAHL, and guideline databases., Review Methods: Guideline search strategies, supplemented by database searches on sudden sensorineural hearing loss (SSNHL), idiopathic facial nerve paralysis (Bell's palsy), sinonasal polyposis, laryngotracheal disorders, head and neck oncology, and pediatric otolaryngology, prioritizing systematic reviews, randomized controlled trials, and COVID-19-specific findings., Conclusions: Systemic corticosteroids (SCSs) reduce long-term morbidity in individuals with SSNHL and Bell's palsy, reduce acute laryngotracheal edema, and have benefit in perioperative management for some procedures. Topical or locally injected corticosteroids are preferable for most other otolaryngologic indications. SCSs have not shown long-term benefit for sinonasal disorders. SCSs are not a contraindication to vaccination with COVID-19 vaccines approved by the US Food and Drug Administration. The Centers for Disease Control and Prevention noted that these vaccines are safe for immunocompromised patients., Implications for Practice: SCS use for SSNHL, Bell's palsy, laryngotracheal edema, and perioperative care should follow prepandemic standards. Local or topical corticosteroids are preferable for most other otolaryngologic indications. Whether SCSs attenuate response to vaccination against COVID-19 or increase susceptibility to SARS-CoV-2 infection is unknown. Immunosuppression may lower vaccine efficacy, so immunocompromised patients should adhere to recommended infection control practices. COVID-19 vaccination with Pfizer-BioNTech, Moderna, or Johnson & Johnson vaccines is safe for immunocompromised patients.

Chromosomes readily unlink and segregate to daughter cells during cell division, highlighting a remarkable ability of cells to organize long DNA molecules. SMC complexes promote DNA organization by loop extrusion. In most bacteria, chromosome folding initiates at dedicated start sites marked by the ParB/parS partition complexes. Whether SMC complexes recognize a specific DNA structure in the partition complex or a protein component is unclear. By replacing genes in Bacillus subtilis with orthologous sequences from Streptococcus pneumoniae, we show that the three subunits of the bacterial Smc complex together with the ParB protein form a functional module that can organize and segregate foreign chromosomes. Using chimeric proteins and chemical cross-linking, we find that ParB directly binds the Smc subunit. We map an interface to the Smc joint and the ParB CTP-binding domain. Structure prediction indicates how the ParB clamp presents DNA to the Smc complex, presumably to initiate DNA loop extrusion., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.)