Reverse Vaccinology and Immunoinformatic Approach for Designing a Bivalent Vaccine Candidate Against Hepatitis A and Hepatitis B Viruses.

Hepatitis A and B are two crucial viral infections that still dramatically affect public health worldwide. Hepatitis A Virus (HAV) is the main cause of acute hepatitis, whereas Hepatitis B Virus (HBV) leads to the chronic form of the disease, possibly cirrhosis or liver failure. Therefore, vaccination has always been considered the most effective preventive method against pathogens. At this moment, we aimed at the immunoinformatic analysis of HAV-Viral Protein 1 (VP1) as the major capsid protein to come up with the most conserved immunogenic truncated protein to be fused by HBV surface antigen (HBs Ag) to achieve a bivalent vaccine against HAV and HBV using an AAY linker. Various computational approaches were employed to predict highly conserved regions and the most immunogenic B-cell and T-cell epitopes of HAV-VP1 capsid protein in both humans and BALB/c. Moreover, the predicted fusion protein was analyzed regarding primary and secondary structures and also homology validation. Afterward, the three-dimensional structure of vaccine constructs docked with various toll-like receptors (TLR) 2, 4 and 7. According to the bioinformatics tools, the region of 99-259 amino acids of VP1 was selected with high immunogenicity and conserved epitopes. T-cell epitope prediction showed that this region contains 32 antigenic peptides for Human leukocyte antigen (HLA) class I and 20 antigenic peptides in terms of HLA class II which are almost fully conserved in the Iranian population. The vaccine design includes 5 linear and 4 conformational B-cell lymphocyte (BCL) epitopes to induce humoral immune responses. The designed VP1-AAY-HBsAg fusion protein has the potency to be constructed and expressed to achieve a bivalent vaccine candidate, especially in the Iranian population. These findings led us to claim that the designed vaccine candidate provides potential pathways for creating an exploratory vaccine against Hepatitis A and Hepatitis B Viruses with high confidence for the identified strains.

Facial nerve hemangioma: a rare case involving the vertical segment.

This case report and literature review reports on a rare case of facial nerve hemangioma (FNH) involving the vertical facial nerve (FN) segment, and discusses the clinical presentation, imaging, pathogenesis, and management of these rare lesions. A 53-year-old male presented with a 10-year history of right hemifacial twitching and progressive facial paresis (House-Brackmann grading score V/VI). The computed tomography and magnetic resonance imaging studies confirmed an expansile lesion along the vertical FN segment. Excision and histopathologic examination demonstrated FNH. FNHs involving the vertical FN segment are extremely rare. Despite being rare lesions, we believe that familiarity with the presentation and management of FNHs are imperative. Laryngoscope, 2012.

Patterns of cervical lymph node metastases in primary and recurrent papillary thyroid cancer.

The incidence of thyroid cancer is rising in the United States with papillary thyroid cancer (PTC) being the most common type. We performed a retrospective study of 49 patients with PTC who underwent 57 lateral neck dissections (NDs). The extent of NDs varied, but 29 of 57 (51%) consisted of levels II-V. Twelve of 57 (21%) NDs consisted of levels I-V. Twelve of 57 (21%) NDs consisted of levels II-IV. One of 57 (1.8%) necks involved only levels I-IV. One of 57(1.8%) necks involved only levels I-V. One of 57(1.8%) necks involved only levels III-V. Two (3.5%) double-level (III-IV) neck surgeries were also performed. Metastatic PTC adenopathy was confirmed pathologically in 2%-level-I, 45%-level-II, 57%-level-III, 60%-level-IV, and 22%-level-V necks. Level-V was positive in 21% of primary and 24% of recurrent groups (P = 0.76). Comparing primary and recurrent disease, there was no difference in nodal distribution or frequency for levels I, II, III, and V. Level-IV was more common in the recurrent cases (P = 0.05). Based on the pathologic distribution of nodes, dissection should routinely include levels II-IV and extend to level-V in primary and recurrent cases. Our data does not suggest routine dissection of level-I.

Cryopyrin-associated periodic syndromes: otolaryngologic and audiologic manifestations.

OBJECTIVE: Cryopyrin-associated periodic syndromes (CAPS) represent a spectrum of CIAS1 gene-mediated autoinflammatory diseases characterized by recurrent systemic inflammation. The clinical spectrum of CAPS varies from mild to severe and includes the syndromes historically described as familial cold autoinflammatory syndrome (FCAS), Muckle-Wells syndrome (MWS), and neonatal-onset multisystem inflammatory disease (NOMID). This article presents the largest cohort of patients with CAPS. The objective is to describe the pathogenesis, otolaryngologic, and audiologic manifestations of CAPS. STUDY DESIGN: Prospective (2003-2009). SETTING: National Institutes of Health. SUBJECTS AND METHODS: Fifty-seven patients with a diagnosis of CAPS were identified (31 NOMID, 11 NOMID/MWS, 9 MWS, and 6 FCAS). Comprehensive data regarding clinical manifestations, audiologic phenotype, and fluid attenuation inversion recovery MRI (FLAIR-MRI) of the brain and inner ear were obtained. RESULTS: Complete audiologic data obtained on 70% of ears revealed conductive hearing loss in 4 (11%) NOMID ears and mixed hearing loss in 5 (13%) NOMID and 2 (14%) NOMID/MWS ears. Sensorineural hearing loss (SNHL), worse in higher frequencies, was the most common type of hearing loss and was present in 23 (61%) NOMID, 10 (71%) NOMID/MWS, and 4 (33%) MWS ears. All of the patients with FCAS had normal hearing except 2, who had SNHL from 4 to 8 kHz. On FLAIR-MRI sequence, cochlear enhancement was noted in 26 of 29 (90%) NOMID, 6 of 11 (55%) NOMID/MWS, 3 of 9 (33%) MWS, and 1 of 6 (17%) FCAS patients and was significantly associated with the presence of hearing loss. Maxillary sinus hypoplasia and mucosal thickening were found in 39% and 86% of the cohort, respectively. CONCLUSION: CIAS1 pathway­mediated CAPS is associated with unregulated autoinflammation mediated by interleukin-1 in the cochlea and hearing loss. Timely diagnosis is crucial to initiate early treatment with interleukin-1 receptor antagonists.

Melanocytic nevi with Spitz differentiation: diagnosis and management.

OBJECTIVES: Melanocytic proliferations with Spitz differentiation present a difficult clinicopathologic dilemma, as their spectrum ranges from benign to malignant. Distinct entities include Spitz nevus, atypical Spitz nevus, and Spitzoid melanoma. Their histopathologic differentiation can be challenging, and cases of Spitzoid melanoma initially diagnosed as benign Spitz nevi are reported in the literature. The goal of this article is to discuss the diagnostic tools (including comparative genomic hybridization), which may be helpful in differentiating benign Spitz nevi from malignant melanoma with Spitzoid features, and to propose an appropriate management strategy for each entity. STUDY DESIGN: Retrospective case reports. METHODS: Medical records of patients referred for suspicious nevi were reviewed. Data regarding demographics, site, pathology reports, and treatment were reviewed. RESULTS: Four patients with three distinct diagnoses involving Spitz differentiation were identified. The pathologic interpretation of these biopsies was difficult and multiple dermatopathologists were involved. All four patients underwent excision with or without sentinel node biopsy. CONCLUSIONS: Otolaryngologists, plastic surgeons and dermatopathologists will encounter patients who have melanocytic lesions with Spitz differentiation at some point in their career. The management of these patients is significantly impacted by the histopathologic diagnosis, and should not be undertaken until it is confirmed, possibly with comparative genomic hybridization. In our experience, it is not unusual to have multiple independent pathologic examinations. We believe that a team approach between the surgeon and the dermatopathologist is crucial when diagnosing and managing patients with Spitz lesions.

Decreased risk of squamous cell carcinoma of the head and neck in users of nonsteroidal anti-inflammatory drugs.

We evaluated the chemopreventive effect of nonsteroidal anti-inflammatory drug (NSAID) use in head and neck squamous cell carcinomas (HNSCC) by conducting a case-control study based on the administration of a standardized questionnaire to 71 incident HNSCC cases and same number of healthy controls. NSAID use was associated with a 75% reduction in risk of developing HNSCC. A significant risk reduction was noted in association with frequency of NSAID use. Restricting the analysis to aspirin users revealed a significant 90% reduction in risk of developing HNSCC. This study provides evidence for a significant reduction in the risk of developing HNSCC in users of NSAIDs, and specifically aspirin users.