Management Practices for Standard-Risk and High-Risk Patients With Bronchiolitis.

OBJECTIVE: Management guidelines for bronchiolitis advocate for supportive care and exclude those with high-risk conditions. We aim to describe and compare the management of standard-risk and high-risk patients with bronchiolitis. METHODS: This retrospective study examined patients <2 years of age admitted to the general pediatric ward with an International Classification of Diseases, 10th Revision discharge diagnosis code of bronchiolitis or viral syndrome with evidence of lower respiratory tract involvement. Patients were defined as either standard- or high-risk on the basis of previously published criteria. The frequencies of diagnostic and therapeutic interventions were compared. RESULTS: We included 265 patients in this study (122 standard-risk [46.0%], 143 high-risk [54.0%]). Increased bronchodilator use was observed in the standard-risk group (any albuterol dosing, standard-risk 65.6%, high-risk 44.1%, P = .003). Increased steroid use was observed in the standard-risk group (any steroid dosing, standard-risk 19.7%, high-risk 14.7%, P = .018). Multiple logistic regression revealed >3 doses of albuterol, hypertonic saline, and chest physiotherapy use to be associated with rapid response team activation (odds ratio [OR] >3 doses albuterol: 8.36 [95% confidence interval (CI): 1.99-35.10], P = .048; OR >3 doses hypertonic saline: 13.94 [95% CI: 4.32-44.92], P = .001); OR percussion and postural drainage: 5.06 [95% CI: 1.88-13.63], P = .017). CONCLUSIONS: A varied approach to the management of bronchiolitis in both standard-risk and high-risk children occurred institutionally. Bronchodilators and steroids continue to be used frequently despite practice recommendations and regardless of risk status. More research is needed on management strategies in patients at high-risk for severe disease.

Case Report: Group B Streptococcus meningitis in an adolescent .

Streptococcus agalactiae (group B Streptococcus, GBS) usually colonizes the gastrointestinal and lower genital tracts of asymptomatic hosts, yet the incidence of invasive disease is on the rise . We describe a case of an 18 year old woman, recently diagnosed with lupus, who reported a spontaneous abortion six weeks prior to her hospitalization.  She presented with fever, altered mental status, and meningeal signs, paired with a positive blood culture for GBS. Magnetic resonance imaging of her brain demonstrated an extra-axial fluid collection, and she was diagnosed with meningitis.  She received prolonged intravenous antibiotic therapy and aggressive treatment for lupus, leading to clinical recovery. This case illustrates the importance of recognizing GBS as a potential pathogen in all patients presenting with CNS infection .  

In vivo electroporation enhances the immunogenicity of an HIV-1 DNA vaccine candidate in healthy volunteers.

BACKGROUND: DNA-based vaccines have been safe but weakly immunogenic in humans to date. METHODS AND FINDINGS: We sought to determine the safety, tolerability, and immunogenicity of ADVAX, a multigenic HIV-1 DNA vaccine candidate, injected intramuscularly by in vivo electroporation (EP) in a Phase-1, double-blind, randomized placebo-controlled trial in healthy volunteers. Eight volunteers each received 0.2 mg, 1 mg, or 4 mg ADVAX or saline placebo via EP, or 4 mg ADVAX via standard intramuscular injection at weeks 0 and 8. A third vaccination was administered to eleven volunteers at week 36. EP was safe, well-tolerated and considered acceptable for a prophylactic vaccine. EP delivery of ADVAX increased the magnitude of HIV-1-specific cell mediated immunity by up to 70-fold over IM injection, as measured by gamma interferon ELISpot. The number of antigens to which the response was detected improved with EP and increasing dosage. Intracellular cytokine staining analysis of ELISpot responders revealed both CD4+ and CD8+ T cell responses, with co-secretion of multiple cytokines. CONCLUSIONS: This is the first demonstration in healthy volunteers that EP is safe, tolerable, and effective in improving the magnitude, breadth and durability of cellular immune responses to a DNA vaccine candidate. TRIAL REGISTRATION: ClinicalTrials.gov NCT00545987.

Immunogenicity, safety, biodistribution and persistence of ADVAX, a prophylactic DNA vaccine for HIV-1, delivered by in vivo electroporation.

ADVAX is a DNA-based candidate HIV vaccine that was safe but weakly immunogenic when delivered intramuscularly (IM) in humans. Studies were performed in animal models to determine whether an alternative delivery method, in vivo electroporation (EP), could improve the immunogenicity of ADVAX while maintaining an acceptable safety profile. Immunization of mice with ADVAX with or without EP at weeks 0, 3, and 6, revealed significantly higher gamma interferon ELISpot responses to all antigens in the EP groups. Antigen-specific CD4+ and CD8+ T cell responses, as quantified by intracellular cytokine staining, both improved significantly with EP. Evaluation of repeat-dose toxicity of ADVAX-EP in rabbits did not reveal any safety concerns. Biodistribution studies of ADVAX delivered IM and with EP in rats indicated that the vaccine was localized predominantly to the administration site in both groups. PCR-based quantitation of residual plasmid at Day 60 indicated that the potential for integration events into the host genome was low for both IM and EP delivery. Taken together, these data supported the clinical development of ADVAX delivered with EP in human volunteers.

Grape-seed polyphenolic extract improves the eye phenotype in a Drosophila model of tauopathy.

Drosophila models of tauopathies have been developed by transgenically overexpressing the disease-associated forms of tau. In this paper we report for the first time that a recently developed Grape-Seed Polyphenolic Extract (GSPE) improves the eye phenotype of a Drosophila eye model of R406W tau. GSPE-mediated improvements in this distinct in vivo neurodegeneration model for protein misfolding/aggregation suggest that GSPE may have therapeutic value in disorders involving aberrant protein aggregation.

POTENTIAL APPLICATION OF GRAPE DERIVED POLYPHENOLS IN HUNTINGTON'S DISEASE.

Huntington's disease (HD) is a progressive neurodegenerative disorder associated with selective neuronal cell death. Abnormal aggregation of huntingtin protein with polyQ expansion has been shown to be causally linked to HD. Grape seed polyphenolic extract (GSPE) is a natural compound that has previously been shown to interfere with aggregations of proteins involved in neurological disorders, such as amyloid beta peptides (Aß) and Tau protein. In this study we found that GSPE treatment significantly inhibits polyQ aggregation in phaeochromocytoma (PC)-12 cell line containing an ecdysone-inducible protein comprising the first 17 amino acid of huntingtin plus 103 glutamines fused with enhanced GFP. In vivo feasibility studies using the Q93httexon1 drosophila model of HD, we extended our in vitro evidence and found that flies fed with GSPE had a significantly improved lifespan compared to the control flies. Using the R6/2 rodent model of HD, we found that oral administration of 100 mg/kg/day GSPE (equivalent to 500mg per day in human) significantly attenuated the motor skill decay as well as extended the lifespan in the R6/2 mice relative to vehicle-control mice. Collectively, our studies strongly suggest that GSPE might be able to modulate the onset and/or progression of HD.