SUMMARYLittle data are available on cellular immune responses during infection with hepatitis E virus (HEV). We therefore mapped CD4 T-cell epitopes in open reading frame (ORF)2 and ORF3 proteins of HEV using lymphocyte proliferation assays and overlapping peptide libraries. Proliferation of peripheral blood mononuclear cells from 40 patients with acute hepatitis E and 21 healthy controls with recombinant HEV ORF2 protein or pools of overlapping HEV ORF2/ORF3 peptides was measured. HLA-DQB1 and HLA-DRB1 alleles were also determined. Mononuclear cells from patients with hepatitis E more often showed significant proliferation on stimulation with recombinant ORF2 protein than controls (32/40 vs 7/21), and had higher median (range) stimulation indices [2.6 (0.9-15.2) vs 1.3 (0.6-12.9)]. Peptide pools corresponding to amino acids 73-156, 289-372, 361-444 and 505-588 of HEV ORF2 protein were associated with significant proliferation. Individual peptides in these pools did not show a clear pattern of stimulation. HEV ORF3 peptide pools did not induce proliferative responses. Lymphocyte proliferation in response to the peptide pool corresponding to amino acids 289-372 of HEV ORF2 protein was associated with presence of HLA-DRB1 allele 010X. These data on mapping of T-cell epitopes in HEV proteins may prove useful for designing HEV vaccines and for studying the immunopathogenesis of hepatitis E.

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BackgroundDengue is today the most significant of arboviral diseases. Novel tools are necessary to effectively address the problem of dengue. Virus-like particles (VLP) offer a versatile nanoscale platform for developing tools with potential biomedical applications. From the perspective of a potentially useful dengue-specific tool, the dengue virus envelope protein domain III (EDIII), endowed with serotype-specificity, host receptor recognition and the capacity to elicit virus-neutralizing antibodies, is an attractive candidate.MethodsWe have developed a strategy to co-express and co-purify Hepatitis B virus surface (S) antigen in two forms: independently and as a fusion with EDIII. We characterized these physically and functionally.ResultsThe two forms of the S antigen associate into VLPs. The ability of these to display EDIII in a functionally accessible manner is dependent upon the relative levels of the two forms of the S antigen. Mosaic VLPs containing the fused and un-fused components in 1:4 ratio displayed maximal functional competence.ConclusionsVLPs armed with EDIII may be potentially useful in diagnostic, therapeutic and prophylactic applications.

Study Design. Retrospective Review. Objective. The objective of this study was to determine differences in surgical and post-operative outcomes in AIS patients undergoing spinal deformity correction surgery using standard or large pedicle screw size. Summary of Background. Use of pedicle screw fixation in spinal deformity correction surgery is considered safe and effective. Still, the small size of the pedicle and the complex 3D anatomy of the thoracic spine makes screw placement challenging, with improper pedicle screw fixation leading to catastrophic complications including injuries to nerve roots, spinal cord, and major vessels. Thus, insertion of larger diameter screw sizes has raised concerns amongst surgeons, especially in the pediatric population. Materials and Methods. AIS patients undergoing PSF between 2013 and 2019 were included. Demographic, radiographic, and operative outcomes collected. Patients in the large screw size group (GpI) received 6.5 mm diameter screw sizes at all levels while standard screw size group (GpII) received 5.0 to 5.5 mm diameter screw sizes at all levels. Kruskall-Wallis and Fisher’s exact test performed for continuous and categorical variables respectively. Subanalyses included (1) screw accuracy in patients with available CT scans, (2) stratified analysis of large- and standard-screw patients with ≥60% flexibility rate, (3) stratified analysis of large- and standard-screw patients with <60% flexibility rate, and (4) matched analysis of large- and standard-screw patients by surgeon and year of surgery. Results. GpI patients experienced significantly higher overall curve correction (P<0.001), with 87.6% experiencing at least one grade reduction of apical vertebral rotation from preoperative to postoperative visit(P=0.008). Patients with larger screws displayed higher postoperative kyphosis. No patient experienced medial breaching. Conclusion. Large screw sizes have similar safety profiles to standard screws without negatively impacting surgical and perioperative outcomes in AIS patients undergoing PSF. Additionally, coronal, sagittal, and rotational correction is superior for larger-diameter screws in AIS patients.

Background: Pain is an unpleasant sensory and emotional experience associated with actual or potential tissue damage or described in terms of such damage. In spite of many advances in pain research, we are unable to deal in an effective way. The cost for new drug development is increasing day by day. Drug repurposing is an approach to look for new use in drugs that are already approved for other indications. Mexiletine is a sodium channel blockers that is being approved for treatment of arrhythmias. It is being tried in treatment of various painful conditions. The present study is to evaluate the dose-dependent analgesic activity of mexiletine with ibuprofen.Methods: The analgesic activity of mexiletine was compared at doses of 15mg/kg, 30mg/kg and 45mg/kg with the standard dose of ibuprofen at 10mg/kg in male Wistar rats in thermal model of tail flick analgesiometer.Results: At lower doses (15mg/kg) of mexiletine, analgesic activity of ibuprofen was significantly higher. At higher doses (30 mg/kg and 45 mg/kg) of mexiletine, it was observed that there is no significant difference between the analgesic activities of both drugs.Conclusions: Mexiletine demonstrated a dose-dependent analgesic activity. There was no statistically significant difference between the analgesic activities of higher doses of mexiletine when compared to ibuprofen.