The Effect of Paternal Age on Relapse in First-Episode Schizophrenia

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Age-specific incidence rate in severe or symptomatic infection due to pandemic H1N1 2009 influenza virus

Poster Abstract Session - Influenza and H1N1 Diagnosis, Epidemiology, and Viral Outcome: abstract no. 1133BACKGROUND: Age-specific incidence of the 2009 pandemic influenza provides the scientific basis of public health policies and the basic science research on the age-related susceptibility to influenza. While previous epidemiological studies provided vital information for public health policies, most did not incorporate age-specific data of asymptomatic, symptomatic and severe infection in the analysis. In this study, we incorporated data from seroprevalence and microbiologically-confirmed infection to estimate the relative impact of the pandemic influenza on various age groups. METHODS: For the determination of pre-pandemic and post-pandemic seroprevalence, archived plasma samples randomly collected at the clinical biochemistry department of Queen Mary Hospital in the years 2007 and 2010 were used respectively. Microbiologically-confirmed cases and severe cases reported to the Centre for Health Protection (CHP) from May 1, 2009 to May 23, 2010 were included in our analysis. This study was approved by the institutional review board of the Hospital Authority of Hong Kong. RESULTS: 795 and 1000 plasma samples were collected in 2007 and 2010 respectively. In 2007, 8.7% and 14.2% of individuals had HI titers ≥40 and ≥10 respectively. The pre-existing cross-reactive antibodies were mainly found in patients aged >70 years old. In 2010, the overall proportion of individuals with HI titers ≥40 and ≥10 is 23.2% and 42.2%. The highest overall microbiologically-confirmed incidence rate was found in the 0-10 year age group, and decreased with increasing age (ρ=-1.0, p<0.01). A total of 282 severe cases were reported with a mean age was 47.6 years. The incidence rate of severe cases showed an apparent bimodal age distribution, with higher incidence rate in the age group 0-10 and those older than 50 years old, and the highest incidence rate being those between 51 and 60 years old. CONCLUSION: While the young adults were most commonly infected, the clinical consequence is most alarming in children and older adults aged over 50 years. Public policies should continue to target this high risk group.published_or_final_versionThe 49th Annual Meeting of the Infectious Diseases Society of America (IDSA 2011), Boston, MA., 20-23 October 2011

Analytical Sensitivity of Seven Point-of-Care Influenza Virus Detection Tests and Two Molecular Tests for Detection of Avian Origin H7N9 and Swine Origin H3N2 Variant Influenza A Viruses

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Assessment of Antigen and Molecular Tests with Serial Specimens from a Patient with Influenza A(H7N9) Infection

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Immunogenicity of Intradermal Trivalent Influenza Vaccine with Topical Imiquimod, a Double Blind Randomized Controlled Trial

Imiquimod, a synthetic Toll-like receptor 7 agonist enhanced immunogenicity of influenza vaccine in a mouse model. We hypothesized that topical imiquimod before intradermal influenza vaccination (TIV) would produce similar effect in human. Methods.We performed a prospective 1-year follow-up, double-blind, randomized, controlled trial with adults with comorbidities. Participants were randomized to 1 of the following 3 vaccinations: topical 5% 250 mg imiquimod ointment followed by intradermal TIV, topical aqueous-cream followed by intradermal TIV, or topical aqueous-cream followed by intramuscular TIV. Patients and investigators were blinded to the type of topical treatment applied. Hemagglutination inhibition (HI) and microneutralization antibody titers were measured. The primary outcome was the day 7 seroconversion rate. Results.Ninety-one recruited participants completed the study. The median age was 73 years. On day 7, 27/30 (90%) patients who received imiquimod and intradermal TIV achieved seroconversion against the H1N1 strain by HI, compared with 4/30 (13.3%) who received aqueous-cream and intramuscular TIV (P <. 001), and 12/31 (38.7%) who received aqueous-cream and intradermal TIV (P <. 001). The seroconversion, seroprotection, and geometric mean titer-fold increase were met in all 3 strains in the imiquimod and intradermal TIV group 2 weeks earlier, and the better seroconversion rate was sustained from day 7 to year 1 (P ≤. 001). The better immunogenicity was associated with fewer hospitalizations for influenza or pneumonia (P <. 05). All adverse reactions were self-limited. Conclusions.Pretreatment with topical imiquimod significantly expedited, augmented, and prolonged the immunogenicity of influenza vaccination. This strategy for influenza immunization should be considered for the elderly population. © 2014 The Author

Preclinical evaluation of the AKT inhibitor MK-2206 in nasopharyngeal carcinoma cell lines

Nasopharyngeal carcinoma (NPC) is endemic to Asia and over 40 % of NPC tissues harbor PIK3CA amplifications. This study characterized the preclinical activity of MK-2206, an oral allosteric inhibitor of AKT in 6 NPC cell lines: C666-1, HK1, HONE-1-EBV, HONE-1, CNE-2 and HNE-1. Exposure to increasing concentrations of MK-2206 resulted in over 95 % of growth inhibition in all NPC cell lines with IC50 values in the low micromolar range. Further experiments were performed in 3 representative NPC cell lines: CNE-2 (harbor PIK3CA mutation and most sensitive to MK-2206), C666-1 (carries PIK3CA amplification), and HONE-1-EBV (least sensitive to MK-2206). MK-2206 induced G0/G1 cycle arrest in all 3 cell lines, but could induce apoptosis only in CNE-2 cells. MK-2206 significantly abrogated AKT signaling in all 3 cell lines by inhibiting the activation of AKT and its downstream effectors (FKHR, GSK3β and BAD). MK-2206 also reduced mTOR signaling by reducing activation of mTOR and its downstream 4E-BP1 and p70S6 kinase. MAPK activation was observed in HONE-1 and C666-1 cells, but not in CNE-2 cells following exposure to MK-2206. The addition of MK-2206 to cisplatin (but not with paclitaxel) has a supra-additive inhibitory effect on growth in vitro. In summary, MK-2206 can inhibit growth and abrogate AKT and mTOR signaling in NPC cell lines. This agent is currently being evaluated in a phase II study in metastatic NPC. © 2012 Springer Science+Business Media New York.link_to_subscribed_fulltex