Gonococcal Mimitope Vaccine Candidate Forms a Beta-Hairpin Turn and Binds Hydrophobically to a Therapeutic Monoclonal Antibody.

The spread of multidrug-resistant strains of Neisseria gonorrhoeae, the etiologic agent of gonorrhea, represents a global health emergency. Therefore, the development of a safe and effective vaccine against gonorrhea is urgently needed. In previous studies, murine monoclonal antibody (mAb) 2C7 was raised against gonococcal lipooligosaccharide (LOS). mAb 2C7 elicits complement-dependent bactericidal activity against gonococci, and its glycan epitope is expressed by almost every clinical isolate. Furthermore, we identified a peptide, cyclic peptide 2 (CP2) that mimicked the 2C7 LOS epitope, elicited bactericidal antibodies in mice, and actively protected in a mouse vaginal colonization model. In this study, we performed structural analyses of mAb 2C7 and its complex with the CP2 peptide by X-ray crystallography, NMR spectroscopy, and molecular dynamics (MD) simulations. The crystal structure of Fab 2C7 bound to CP2 showed that the peptide adopted a beta-hairpin conformation and bound the Fab primarily through hydrophobic interactions. We employed NMR spectroscopy and MD simulations to map the 2C7 epitope and identify the bioactive conformation of CP2. We also used small-angle X-ray scattering (SAXS) and native mass spectrometry to obtain further information about the shape and assembly state of the complex. Collectively, our new structural information suggests strategies for humanizing mAb 2C7 as a therapeutic against gonococcal infection and for optimizing peptide CP2 as a vaccine antigen.

High Prevalence of Spinal Magnetic Resonance Imaging Findings in Asymptomatic Young Adults (18-22 Yrs) Candidate to Air Force Flight.

STUDY DESIGN: Cross-sectional, retrospective, magnetic resonance (MR) imaging study, performed during cadets' selection procedures of the Italian Air Force Academy. OBJECTIVE: To assess the prevalence of spinal MR imaging findings in asymptomatic young adults (18-22 yrs) candidate to Air Force Flight. SUMMARY OF BACKGROUND DATA: Spinal MR imaging findings are frequently detected in asymptomatic subjects. Literature prevalence data come from studies that analyze different patient populations, in a wide age range and in different spinal tracts. Chronic degenerative disease of the vertebral column often occurs in pilots exposed to high flight acceleration forces, thus resulting crucial for Air Force Academy to exclude vertebral disease in cadets. METHODS: Three hundred fifty asymptomatic young adults underwent a 3T MR examination of the entire spine. A structured radiological report was set up to classify and calculate the prevalence of spinal MR imaging findings. RESULTS: Two hundred seventy of 350 subjects (77%) presented spinal MR findings, while 80 of 350 candidates (23%) had no detectable MR imaging findings. One hundred six of 350 (30%) candidates had at least one disc desiccation and 47 of 350 (13%) presented at least one disc narrowing. Disc bulging was found in 176 of 350 (49%) cadets. Sixty-two of 350 (18%) subjects showed disc protrusion while 28 of 350 (8%) had disc extrusion. Forty-five of 350 (13%) candidates presented low grade intervertebral spondylosis and of these 12 had also facet joints spondylosis. Asymptomatic vertebral fractures were observed in 2 of 350 (<1%) cadets. CONCLUSION: A high rate of MR spinal imaging findings, similar to that of the adult population, was detected in our population of young asymptomatic subjects. Our results suggest that the process of aging spine, which is supposed to begin in the second decade of life, is morphologically appreciable in the immediate postadolescent period and this issue is of crucial importance when selecting military pilots. LEVEL OF EVIDENCE: 4.

The bilobed flap in skin cancer of the face: our experience on 285 cases.

BACKGROUND: This article describes how many of the defects caused by oncological surgery can be closed with an easily estended flap. PATIENT AND METHOD: The Zitelli bilobed flap was used to treat 285 consecutive patients with basal cell carcinomas (BCCs) or squamous cell carcinomas (SCCs); 167 men (58.60%) and 118 women (41.40%) between 45 and 98 years of age. Histologically, 247 BCCs (86.6%) and 38 SCCs (13.4%) were documented. Regarding the site, 148 (51.9%) involved the nose, 51 (17.9%) the cheeks, 36 (12.6%) the preauricular region, 27 (9.5%) the perilabial region and chin and 23 (8.1%) the periorbital region. To measure long-term satisfaction patients responded to a telephone survey consisting of a single global question. RESULTS: The size of the defect following tumour removal was between 1 and 4cm. Carcinomas up to 1cm were treated using a one step procedure with a cryostat test of the surgical margins; all others cases were treated using two step procedure after excision and histological in sano resection. Completely acceptable aesthetic and functional deficits were obtained in 275 (96.4%) patients over a 6-72-month follow-up. Ten (3.6%) patients suffered postoperative complications. Two cases of local infection; one case of completely flap necrosis and seven cases of partial revision due to flap necrosis occurred. The level of satisfaction with the surgical long-term result reported by the patients was high. CONCLUSION: In our experience the bilobed Zitelli flap for covering defects in the area of the face showed very few complications and good aesthetic results.

Surgical treatment of lip cancer: our experience with 106 cases.

PURPOSE: To report our experience with 106 cases of lip cancer. PATIENTS AND METHODS: We treated 106 patients with stages T1, T2, or T3 lip cancer (76, 22, and 8 cases, respectively). For the 34 T1 lesions up to 1 cm in diameter, we used a V or W excision. In the 42 T1 lesions greater than 1 cm and the 20 T2 lesions, we used the staircase technique. In 2 T2 cases, the carcinoma was located on the labial commissure and was treated with the Fries technique. For the 8 T3 cases, we used the Bernard-Freeman-Fries technique. In 28 patients, a lip shave was performed and tumor was removed. The 7 patients who were N+ at diagnosis underwent modified radical neck dissection and radiotherapy. RESULTS: Ten patients died during the follow-up period of 11 to 65 months: 8 of unrelated causes and 2 of new upper aerodigestive tract carcinoma. None of the patients died of their lip cancer. CONCLUSIONS: Lip cancer is a frequent disease of the oral cavity. Although general agreement has been reached concerning stage T and N+ surgical treatment, unresolved questions remain with regard to N0 treatment. We present our experience and suggestions.