Type D Personality Is Associated with Psychological Distress and Poor Self-Rated Health among the Elderly: A Population-Based Study in Japan

We investigated the association between Type D personality, psychological distress, and self-ratings of poor health in elderly Japanese people. In August 2010, questionnaires were sent to all residents aged >= 65 in three municipalities (n = 21232) in Okayama Prefecture, Japan, and. 13929 questionnaires were returned (response rate: 65.6%). To assess mental and physical health outcomes, we used the Kessler Psychological Distress Scale and a single item question regarding perceived general health. We analyzed 9759 questionnaires to determine odds ratios (ORs) and 95% confidence intervals (CIs) for several health outcomes, adjusting for sex, age, smoking status, frequency of alcohol consumption, overweight status, educational attainment, socioeconomic status, and number of cohabiters. The multiple imputation method was employed for missing data regarding Type D personality. The prevalence of Type D personality in our sample was 46.2%. After adjusting for covariates, we found that participants with Type D personality were at 4-5 times the risk of psychological distress, and twice the risk of poor self-rated health. This association was stronger in participants aged 65-74 years (psychological distress; OR: 5.80, 95% CI: 4.96-6.78, poor self-rated health; OR: 2.84, 95% CI: 2.38-3.38) than in those aged over 75 years (psychological distress; OR: 4.54, 95% CI: 3.96-5.19, poor self-rated health; OR: 2.05, 95% CI: 1.79-2.34). Type D personality is associated with adverse health status among Japanese elderly people in terms of mental and physical risk; therefore, further research into the implications of this personality type is warranted

Phylogenetic Insights into RT and Vpx/Vpr

The efficiency of reverse transcription to synthesize viral DNA in infected cells greatly influences replication kinetics of retroviruses. However, viral replication in non-dividing cells such as resting T cells and terminally differentiated macrophages is potently and kinetically restricted by a host antiviral factor designated SAMHD1 (sterile alpha motif and HD-domain containing protein 1). SAMHD1 reduces cellular deoxynucleoside triphosphate (dNTP) pools and affects viral reverse transcription step. Human immunodeficiency virus type 2 (HIV-2) and some simian immunodeficiency viruses (SIVs) have Vpx or Vpr to efficiently degrade SAMHD1. Interestingly, the reverse transcriptase (RT) derived from HIV-1 that encodes no anti-SAMHD1 proteins has been previously demonstrated to uniquely exhibit a high enzymatic activity. It is thus not irrational to assume that some viruses may have acquired or lost the specific RT property to better adapt themselves to the low dNTP environments confronted in non-dividing cells. This adaptation process may probably be correlated with the SAMHD1-antagonizing ability by viruses. In this report, we asked whether such adaptive events can be inferable from Vpx/Vpr and RT phylogenetic trees overlaid with SAMHD1-degrading capacity of Vpx/Vpr and with kinetic characteristics of RT. Resultant two trees showed substantially similar clustering patterns, and therefore suggested that the properties of RT and Vpx/Vpr can be linked. In other words, HIV/SIVs may possess their own RT proteins to adequately react to various dNTP circumstances in target cells

Phylogenetic Analysis of Vpx/Vpr Expression

Viruses of human immunodeficiency virus type 2 (HIV-2) and some simian immunodeficiency virus (SIV) lineages carry a unique accessory protein called Vpx. Vpx is essential or critical for viral replication in natural target cells such as macrophages and T lymphocytes. We have previously shown that a poly-proline motif (PPM) located at the C-terminal region of Vpx is required for its efficient expression in two strains of HIV-2 and SIVmac, and that the Vpx expression levels of the two clones are significantly different. Notably, the PPM sequence is conserved and confined to Vpx and Vpr proteins derived from certain lineages of HIV-2/SIVs. In this study, Vpx/Vpr proteins from diverse primate lentiviral lineages were experimentally and phylogenetically analyzed to obtain the general expression picture in cells. While both the level and PPM-dependency of Vpx/Vpr expression in transfected cells varied among viral strains, each viral group, based on Vpx/Vpr amino acid sequences, was found to exhibit a characteristic expression profile. Moreover, phylogenetic tree analyses on Gag and Vpx/Vpr proteins gave essentially the same results. Taken together, our study described here suggests that each primate lentiviral lineage may have developed a unique expression pattern of Vpx/Vpr proteins for adaptation to its hostile cellular and species environments in the process of viral evolution

Generation and characterization of new CCR5-tropic HIV-1rmt clones

To develop effective non-human primate models for coping with numerous HIV-1/AIDS studies, rhesus macaque-tropic HIV-1 (HIV-1rmt) clones with a variety of biological properties are required. Such clones, if available, are powerful tools to experimentally elucidate HIV-1 replication and pathogenicity in host individuals, and also to develop anti-HIV-1 drugs/vaccines. However, only limited numbers of HIV-1rmt clones have been currently reported. In the present study, we generated new HIV-1rmt clones carrying various CCR5-tropic env (envelope) genes by standard recombinant DNA and intracellular homologous recombination techniques. Resultant virus clones contain the env sequences derived from an AIDS-inducible laboratory or two clinically isolated viral strains.We further constructed their variant clones bearing N160K, S304G, or G310R mutation in Env that potentially can change the viruses to better grow. Newly generated clones were analyzed for their virological properties such as Env expression, single-cycle infectivity, and multi-cycle replication ability. Out of a number of new clones examined, two were found to grow better in macaque cells than the previously constructed clone used for comparison. Our study described here constitutes the initial and essential step towards obtaining CCR5-tropic HIV-1rmt clones useful for various basic and clinical research projects on infected individuals

Single-amino acid mutation 66SR in Gag-matrix enhances viral single-cycle infectivity of R5-tropic HIV-1rmt

We recently constructed two rhesus macaque-tropic human immunodeficiency virus type 1 (HIV-1 rmt) clones with CXCR-4 or CCR5 tropism, but a CCR5-tropic HIV-1rmt clone grew more poorly than a CXCR4topic clone. It has been demonstrated that interaction between viral Gag-matrix (MA) and Env-gp41 cytoplasmic tail is important for virion-incorporation of Env. Concordantly, Gag-MA mutations (62QR and 66SR) that rescue defects in virion-incorporation of Env/viral replication were reported. In this study, we analyzed effects of these Gag-MA mutations on R5-tropic HIV-1rmt replication potentials. While introduction of 62QR into three HIV-1rmt clones tested reduced their multi-cycle replication ability in rhesus lymphocytes or abolish single-cycle infectivity for luciferase reporter cells, three R5-tropic HIV-1rmt clones carrying 66SR exhibited similar growth kinetics to those of their parental clones. One such clone, 66SR+5gtu, appeared to induce stronger cytopathic effects than parental clone 5gtu. We therefore investigated effects of 66SR mutation on viral replication in more detail. Single-cycle infectivity of 66SR+5gtu was enhanced relative to that of 5gtu, but 66SR+5gtu virion production was significantly decreased compared to the 5gtu level. Gag-MA 66SR mutation may be useful to improve growth potentials of the R5-tropic HIV-1rmt clones

Oseltamivir Prescription and Regulatory Actions Vis-à-Vis Abnormal Behavior Risk in Japan: Drug Utilization Study Using a Nationwide Pharmacy Database

BACKGROUND: In March 2007, a regulatory advisory was issued in Japan to restrict oseltamivir use in children aged 10-19 years because of safety concerns over abnormal behavior. The effectiveness and validity of regulatory risk minimization actions remain to be reviewed, despite their significant public health implications. To assess the impact of the regulatory actions on prescribing practices and safety reporting. METHODOLOY/PRINICPAL FINDINGS: In this retrospective review of a nationwide pharmacy database, we analyzed 100,344 dispensation records for oseltamivir and zanamivir for the period from November 2006 to March 2009. The time trend in dispensations for these antiviral agents was presented before and after the regulatory actions, contrasted with intensity of media coverage and the numbers of spontaneous adverse reaction reports with regard to antivirals. The 2007 regulatory actions, together with its intense media coverage, reduced oseltamivir dispensation in targeted patients in fiscal year 2008 to 20.4% of that in fiscal year 2006, although influenza activities were comparable between these fiscal years. In contrast, zanamivir dispensation increased approximately nine-fold across all age groups. The number of abnormal behavior reports associated with oseltamivir in children aged 10-19 years decreased from fiscal year 2006 to 2008 (24 to 9 cases); this decline was offset by the increased number of reports of abnormal behavior in children under age 10 (12 to 28 cases). The number of reports associated with zanamivir increased in proportion to increased dispensation of this drug (11 to 114 cases). CONCLUSIONS/SIGNIFICANCE: The 2007 actions effectively reduced oseltamivir prescriptions and the number of reports of abnormal behavior in the targeted group. The observed increase in abnormal behavior reports in oseltamivir patients under age 10 and in zanamivir patients suggests that these patient groups may also be at risk, calling into question the validity of the current discrimination by age and agent (Abstract translation is available in Japanese: Appendix S1)

Helical structures of homo-chiral isotope-labeled α-aminoisobutyric acid peptides

The chiral deuterium- and 13C-isotope-labeled α-aminoisobutyric acids CD3-Aib and 13CH3-Aib were enantioselectively synthesized from L-Ala aldimine using simplified Maruoka chiral phase-transfer catalysts. Homo-chiral (S)-CD3-Aib homopeptides, up to decamers, were prepared. A (R)-CD3-Aib polymer and (S)-13CH3-Aib polymer were also prepared. Conformational studies on homopeptides using CD spectra and an X-ray crystallographic analysis revealed that the preferred conformations were 310-helical structures comprising equal amounts of right-handed (P) and left-handed (M) helical-screw structures. The α-carbon chiral centers induced by the D- or 13C-isotope substitution of Aib were incapable of controlling the helical-screw directions of their oligopeptides and short polymers