Chronic,Inhalation Exposure of Rats,Rabbits , and Monkeys to 1 , 2 , 4–Trichlorobenzene

Three groups composed of rats, rabbits, and monkeys were exposed for 26 weeks to 1,2,4-trichlorobenzene (-TCB), and one group of each species was used as a control group. TTie nominal exposure concentrations of 1,2,4-TCB were 25.0, 50.0, and 100.0 ppm. Pulmonary function and operant behavior tests in monkeys, ophthalmoscopic examinations in rabbits and monkeys, and measurement of body weights and hematologic and serum biochemical determinations in all species were conducted before and during the exposure period. At termination of 1, 3, and 6 months of exposure, microscopic examination of selected rat tissues was performed. Microscopic changes were seen in the parenchymal cells of livers and kidneys from all groups of rats exposed to 1,2,4-TCB when sacrificed after 4 and 13 weeks of exposure, but no exposure-related abnormalities or other effects were seen after 26 weeks of exposure in any species.     

Household Transmission of Pandemic (H1N1) 2009, San Antonio, Texas, USA, April�CMay 2009

To assess household transmission of pandemic (H1N1) 2009 in San Antonio, Texas, USA, during April 15–May 8, 2009, we investigated 77 households. The index case-patient was defined as the household member with the earliest onset date of symptoms of acute respiratory infection (ARI), influenza-like illness (ILI), or laboratory-confirmed pandemic (H1N1) 2009. Median interval between illness onset in index and secondary case-patients was 4 days (range 1–9 days); the index case-patient was likely to be <18 years of age (p = 0.034). The secondary attack rate was 4% for pandemic (H1N1) 2009, 9% for ILI, and 13% for ARI. The secondary attack rate was highest for children <5 years of age (8%–19%) and lowest for adults >50 years of age (4%–12%). Early in the outbreak, household transmission primarily occurred from children to other household members and was lower than the transmission rate for seasonal influenza.     

Genistein‐induced upregulation of p21 WAF1 , downregulation of cyclin B,and induction of apoptosis in prostate cancer cells

Increased soy consumption in Asian diets, resulting in increased serum isoflavone levels, has been associated with a decreased risk for prostate adenocarcinoma (PCa). The isoflavone genistein is believed to be the anticancer agent found in soy, and significant levels of genistein have been detected in human prostatic fluid, implicating the role of genistein in PCa prevention. Recent studies have demonstrated genistein's ability to inhibit cell growth and induce apoptosis in several cell lines; however, the molecular mechanisms of genistein's effect are not known. We have evaluated the mechanism by which genistein may inhibit PCa cell growth. Here we report that genistein inhibits PCa cell growth in culture in a dose‐dependent manner, which is accompanied by a G₂/M cell cycle arrest. Cell growth inhibition was observed with concomitant downregulation of cyclin B, upregulation of the p21^WAF1 growth‐inhibitory protein, and induction of apoptosis. Collectively, these results provide experimental evidence for a novel effect of genistein on cell cycle gene regulation, resulting in the inhibition of cell growth and ultimate demise of tumor cells.     

Incidence of Influenza A(H1N1)pdm09 Infection,United Kingdom, 2009–2011

We conducted a longitudinal community cohort study of healthy adults in the UK. We found significantly higher incidence of influenza A(H1N1)pdm09 infection in 2010–11 than in 2009–10, a substantial proportion of subclinical infection, and higher risk for infection during 2010–11 among persons with lower preinfection antibody titers.     

Sustained Transmission of Pertussis in Vaccinated, 1–5-Year-Old Children in a Preschool,Florida, USA

In September 2013, local county health officials in Tallahassee, Florida, USA, were notified of a laboratory-confirmed pertussis case in a 1-year-old preschool attendee. During a 5-month period, 26 (22%) students 1–5 years of age, 2 staff from the same preschool, and 11 family members met the national case definition for pertussis. Four persons during this outbreak were hospitalized for clinical management of pertussis symptoms. Only 5 students, including 2 students with pertussis, had not received the complete series of vaccinations for pertussis. Attack rates in 1 classroom for all students who received the complete series of vaccinations for pertussis approached 50%. This outbreak raises concerns about vaccine effectiveness in this preschool age group and reinforces the idea that recent pertussis vaccination should not dissuade physicians from diagnosing, testing, or treating persons with compatible illness for pertussis.     

Safety, tolerability, and immunogenicity after 1 and 2 doses of zoster vaccine in healthy adults ≥60 years of age

Background

Incidence and severity of herpes zoster (HZ) and postherpetic neuralgia increase with age, associated with age-related decrease in immunity to varicella-zoster virus (VZV). One dose of zoster vaccine (ZV) has demonstrated substantial protection against HZ; this study examined impact of a second dose of ZV.

Methods

Randomized, double-blind, multicenter study with 210 subjects ≥60 years old compared immunity and safety profiles after one and two doses of ZV, separated by 6 weeks, vs. placebo. Immunogenicity was evaluated using VZV interferon-gamma (IFN-γ) enzyme-linked immunospot (ELISPOT) assay and VZV glycoprotein enzyme-linked immunosorbent antibody (gpELISA) assay. Adverse experiences (AEs) were recorded on a standardized Vaccination Report Card.

Results

No serious vaccine-related AEs occurred. VZV IFN-γ ELISPOT geometric mean count (GMC) of spot-forming cells per 10⁶ peripheral blood mononuclear cells increased in the ZV group from 16.9 prevaccination to 49.5 and 32.8 at 2 and 6 weeks postdose 1, respectively. Two weeks, 6 weeks and 6 months postdose 2, GMC was 44.3, 42.9, and 36.5, respectively. GMC in the placebo group did not change during the study. The peak ELISPOT response occurred ∼2 weeks after each ZV dose. The gpELISA geometric mean titers (GMTs) in the ZV group were higher than in the placebo group at 6 weeks after each dose. Correlation between the IFN-γ ELISPOT and gpELISA assays was poor.

Conclusions

ZV was generally well-tolerated and immunogenic in adults ≥60 years old. A second dose of ZV was generally safe, but did not boost VZV-specific immunity beyond levels achieved postdose 1.     

Antimetastatic Effects and Mechanisms of Apo-8′-Lycopenal,an Enzymatic Metabolite of Lycopene,Against Human Hepatocarcinoma SK-Hep-1 Cells

Lycopene is primarily metabolized by carotenoid monoxygenase II into apo-8′- and apo-12′-lycopenal in the rat liver. Although lycopene possesses antimetastatic activity in a highly invasive hepatoma SK-Hep-1 cell line, little is known whether its metabolites have a similar effect. In this study, we investigated the antimetastatic effects of apo-8′-lycopenal (1–10 μM) in comparison with lycopene (10 μM) in SK-Hep-1 cells. We found that both apo-8′-lycopenal and lycopene inhibited the invasion and migration of SK-Hep-1 cells, and the effect of apo-8′-lycopenal was stronger than that of lycopene at the same concentration (10 μM). Mechanistically, apo-8′-lycopenal: 1) decreased the activities and protein expression of metalloproteinase-2 (MMP-2) and ?9; 2) increased the protein expression of nm23-H1 and the tissue inhibitor of MMP (TIMP)-1 and ?2; 3) suppressed protein expression of Rho small GTPases; and 4) inhibited focal adhesion kinase-mediated signaling pathway, such as ERK/p38 and PI3K-Akt axis. Overall, these results demonstrate that apo-8′-lycopenal possesses antimetastatic activity in SK-Hep-1 cells and that this effect is stronger than that of lycopene, suggesting that the antimetastatic effect may be attributed, at least in part, to its metabolites such as apo-8′-lycopenal.     

Increased Number of Human Cases of Influenza Virus A(H5N1) Infection,Egypt, 2014–15

During November 2014–April 2015, a total of 165 case-patients with influenza virus A(H5N1) infection, including 6 clusters and 51 deaths, were identified in Egypt. Among infected persons, 99% reported poultry exposure: 19% to ill poultry and 35% to dead poultry. Only 1 person reported wearing personal protective equipment while working with poultry.     

On the Stability of Reported Pregnancy Intentions from Pregnancy to 1 Year Postnatally: Impact of Choice of Measure,Timing of Assessment,Women’s Characteristics and Outcome of Pregnancy

Objectives

Retrospective, cross-sectional estimates of pregnancy intention, as used in the Demographic Health Survey (DHS), are the global norm. The London Measure of Unplanned Pregnancy (LMUP) is a newer, psychometrically validated measure which may be more reliable. This paper assesses the reliability of the LMUP and the DHS question over the first postnatal year and explores the effects of maternal characteristics or pregnancy outcome on reported pregnancy intention.

Methods

We compared the test–retest reliability of the LMUP (using the AC coefficient) and DHS question (using the weighted Kappa) over the first postnatal year using data from Malawian women. We investigated the effect of maternal characteristics and pregnancy outcome using t-tests, Chi squared or Fisher’s exact tests, and calculated odds ratios to estimate effect size.

Results

The DHS question was associated with a statistically significant decrease in the prevalence of unplanned pregnancies from 1-to-12 months postnatally; the LMUP was not. The LMUP had moderate to substantial reliability (0.51–0.66); the DHS had moderate reliability (0.56–0.58). The LMUP’s stability was not related to any of the factors examined; the stability of the DHS varied by marital status (p?=?0.033), number of children (p?=?0.048) and postnatal depression (p?<?0.001). Both underestimated unintended pregnancy postnatally vis-à-vis the LMUP in pregnancy.

Conclusions for Practice

The LMUP is a more reliable measure of pregnancy intention than the DHS in the first postnatal year and does not vary by maternal characteristics or pregnancy outcome. The LMUP should become the gold-standard for measuring pregnancy intention and should be collected in pregnancy or at the first postnatal opportunity.

     

Occurrence of Panstrongylus lutzi, in peridomiciliary areas, State of Ceará, Brazil

From January 2001 to October 2002 captures were made in domicile and peridomiciliary areas of 13 cities of region of Cariri, south of the State of Ceará. As results, the occurrence of P. lutzi in this area was noticed, for the first time, in three cities: the presence of one adult in chicken house in Altaneira, one adult flying, in Salitre and 18 nymphs in Varzea Alegre(13 in bricks pile and five in roofing tile pile). In Varzea Alegre city it was observed the colonization in the peridomicile.     

Evidence of Vaccine-related Reassortment of Rotavirus,Brazil, 2008–2010

Analysis of 27 rotavirus strains from vaccinated and unvaccinated children revealed reassortment events in 3 strains: a gene derived from a vaccine; a gene acquired from a circulating strain; and reassortment between circulating strains. Data suggest that the widespread use of this monovalent rotavirus vaccine may introduce vaccine genes into circulating human rotaviruses or vice versa.     

Prospective comparison of 6 comorbidity indices as predictors of 1-year post-hospital discharge institutionalization, readmission, and mortality in elderly individuals

BackgroundOlder patients often suffer from multiple comorbid conditions. Few comorbidity indices are valid and reliable in the elderly and were rarely compared.ObjectiveTo compare the performance, relevance, and ability of 6 widely used and validated comorbidity indices—Charlson Comorbidity Index, Cumulative Illness Rating Scale–Geriatrics, Index of Coexistent Diseases, Kaplan, Geriatric Index of Comorbidity (GIC), and Chronic Disease Score—to predict adverse outcomes after discharge (1-year risk of rehospitalization, institutionalization, and death).Design, setting, and participantsProspective study with 1-year follow-up, between January 2004 and December 2005 in 444 elderly patients (mean age, 85; 74% female) discharged from acute geriatric hospital, Geneva University Hospitals.ResultsIn univariate analyses, Cumulative Illness Rating Scale?Geriatrics and GIC were the predictors with the largest coefficient of determination for mortality with (R² of 9.3%, respectively 8.8%). GIC was also the only significant predictor of institutionalization (R² = 6.0%). Higher risk of readmission was significantly associated with GIC (R² = 14.0%), Cumulative Illness Rating Scale–Geriatrics (R² = 5.6%), Charlson Comorbidity Index (R² = 3.1%), and Chronic Disease Score (R² = 1.7).ConclusionsUnderstanding how to efficiently predict these adverse outcomes in hospitalized elders is important for a variety of clinical and policy reasons. GIC and Cumulative Illness Rating Scale–Geriatrics may improve hospital discharge planning in a geriatric hospital treating very old patients with acute disease.     

Oleuropein,a Secoiridoid Derived from Olive Tree,Inhibits the Proliferation of Human Colorectal Cancer Cell Through Downregulation of HIF-1α

Oleuropein (OL) is the most prominent phenolic compound in the fruit of olive tree. Although OL has shown powerful anticancer activity the underlying action mechanism remains largely unknown. The present study evaluated the effects of OL on hydroxityrosol (HT)-29 human colon adenocarcinoma cells in comparison to hydroxytyrosol, its hydrolysis product, and to elucidate the underlying anticancer molecular mechanisms involved. Cell proliferation was determined using SRB assay. Cell cycle and apoptosis were assessed by flow cytometry and changes in MAPK cascade protein expression, HIF-1α, p53, PPARγ, and NFKβ signaling pathways by Western blot. Although OL showed less potency than HT, in terms of cell growth inhibition, induced significant changes in cell cycle analysis and caused a significant increase in the apoptotic population. Both compounds produced a remarkable decrease in HIF-1α protein and an upregulation of p53 protein expression. However, no significant changes in IkB-α and MAPK cascade protein expressions were observed. HT produced a significant upregulation in peroxisome proliferator-activated receptor gamma (PPARγ) expression whereas OL failed. PPARγ upregulation may be one of the principal mechanisms of the tumor shrinkage by HT. Our novel findings demonstrate that OL limits the growth and induces apoptosis in HT-29 cells via p53 pathway activation adapting the HIF-1α response to hypoxia.     

Indicators of therapeutic effect in FIT-06, a Phase II trial of a DNA vaccine, GTU(®)-Multi-HIVB, in untreated HIV-1 infected subjects

Background

Combination highly active antiretroviral therapy (HAART) has significantly decreased HIV-1 related morbidity and mortality globally transforming HIV into a controllable condition. HAART has a number of limitations though, including limited access in resource constrained countries, which have driven the search for simpler, affordable HIV-1 treatment modalities. Therapeutic HIV-1 vaccines aim to provide immunological support to slow disease progression and decrease transmission. We evaluated the safety, immunogenicity and clinical effect of a novel recombinant plasmid DNA therapeutic HIV-1 vaccine, GTU^®-multi-HIVB, containing 6 different genes derived from an HIV-1 subtype B isolate.

Methods

63 untreated, healthy, HIV-1 infected, adults between 18 and 40 years were enrolled in a single-blinded, placebo-controlled Phase II trial in South Africa. Subjects were HIV-1 subtype C infected, had never received antiretrovirals, with CD4 ≥ 350 cells/mm³ and pHIV-RNA ≥ 50 copies/mL at screening. Subjects were allocated to vaccine or placebo groups in a 2:1 ratio either administered intradermally (ID) (0.5 mg/dose) or intramuscularly (IM) (1 mg/dose) at 0, 4 and 12 weeks boosted at 76 and 80 weeks with 1 mg/dose (ID) and 2 mg/dose (IM), respectively. Safety was assessed by adverse event monitoring and immunogenicity by HIV-1-specific CD4+ and CD8+ T-cells using intracellular cytokine staining (ICS), pHIV-RNA and CD4 counts.

Results

Vaccine was safe and well tolerated with no vaccine related serious adverse events. Significant declines in log pHIV-RNA (p = 0.012) and increases in CD4+ T cell counts (p = 0.066) were observed in the vaccine group compared to placebo, more pronounced after IM administration and in some HLA haplotypes (B*5703) maintained for 17 months after the final immunisation.

Conclusions

The GTU^®-multi-HIVB plasmid recombinant DNA therapeutic HIV-1 vaccine is safe, well tolerated and favourably affects pHIV-RNA and CD4 counts in untreated HIV-1infected individuals after IM administration in subjects with HLA B*57, B*8101 and B*5801haplotypes.     

Resveratrol suppressed seizures by attenuating IL-1β, IL1-Ra,IL-6, and TNF-α in the hippocampus and cortex of kindled mice

Objective: There is an urge to identify new molecules which can modulate process of epileptogenesis, since currently available drugs act symptomatically and one-third of the patients remain refractory to the disease. Hence, the present study was conducted to evaluate the effects of Resveratrol (RESV) on epileptogenesis in pentylenetetrazole (PTZ)-induced kindling in mice.

Method: Swiss albino mice were administered RESV (10, 20 and 40?mg/kg,p.o) in acute study. On the seventh day animals were subjected to various neurological and neurobehavioral tests viz, Increasing Current Electroshock Test (ICES), PTZ-induced seizures, passive avoidance response, and elevated plus maze test. For the development of kindling PTZ was administered in a dose of 25?mg/kg, i.p. on every alternate day and RESV in all the three doses was administered daily. Seizure score was continuously monitored till the development of kindling and cognition tests were performed in the end of the study. The animals were sacrificed and levels of inflammatory biomarkers viz., IL-1β, interleukin-1 receptor antagonist (IL1-Ra), IL-6, and TNF-α were assessed in the hippocampus and cortex of the kindled animals.

Results: RESV in all three doses increased the seizure threshold to hind limb extension in the ICES test. RESV in all the tested doses suppressed the development of kindling and reduced the levels of IL-1β, IL1-Ra, IL-6, and TNF-α in kindled mice.

Conclusion: RESV suppressed the development of kindling in mice and decreased the levels of inflammatory biomarkers in their hippocampus. RESV modified brain inflammation during epileptogenesis and found to possess nootropic activity in the kindled mice.     

Abstracts of selected papers from the 1st ISOQOL Pan-Pacific Conference, Tokyo, Japan, April 13–15 2001

Abstract List

Abstracts of selected papers from the 1st ISOQOL Pan-Pacific Conference, Tokyo, Japan, April 13–15 2001