6,7-Dihydro-2-benzothiophen-4(5H)-ones: a novel class of GABA-A alpha5 receptor inverse agonists

Nonselective inverse agonists at the benzodiazepine binding site on the GABA-A chloride ion channel enhance cognitive performance in animals but cannot be used in the treatment of cognitive disorders because of anxiogenic and convulsant side effects. We have identified a novel series of GABA-A alpha5 receptor ligands during our search for alpha5 receptor inverse agonists as potential cognition enhancers. In particular, 6,6-dimethyl-3-(2-hydroxyethyl)thio-1-(thiazol-2-yl)-6,7-dihydro-2-benzothiophen-4(5H)-one (26) has been identified as a functionally selective GABA-A alpha5 inverse agonist.     

Effects of phencyclidine on extracellular levels of dopamine, dihydroxyphenylacetic acid and homovanillic acid in conscious and anesthetized rats

Dose-dependent effects of phencyclidine on extracellular levels of dopamine (DA), dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) in the neostriatum were studied in both urethane-anesthetized and conscious rats. In vivo microdialysis was used to collect 10 min samples that were analyzed for levels of DA, DOPAC and HVA, using high-performance liquid chromatography with electrochemical detection (HPLC-EC). In both the anesthetized and conscious preparations, 20 mg/kg of phencyclidine produced an increase in extracellular levels of DA, 10 mg/kg resulted in no change, while 1 mg/kg produced a slow decrease. In the anesthetized animals phencyclidine did not have a significant effect on levels of DOPAC or HVA, but in the conscious animals phencyclidine produced a dose-dependent decrease in levels of DOPAC and HVA. The increase in levels of DA could be the result of increased release of DA or inhibition of the uptake of DA. The decrease in levels of DOPAC and HVA, at the 1 mg/kg dose, could result from a decrease in the synthesis of DA that is offset at the 10 and 20 mg/kg doses by opposing mechanisms.     

Seasonal influenza vaccine elicits heterosubtypic immunity against H5N1 that can be further boosted by H5N1 vaccination

Recent findings indicate that seasonal influenza vaccination or infection of healthy humans may contribute to heterosubtypic immunity against new influenza A subtypes, such as H5N1. Here, we investigated whether seasonal influenza vaccination in a mouse model could induce any immunity against the H5N1 subtype. It could be demonstrated that, largely due to the H1N1 component strain A/NewCaledonia/20/99, parenteral immunization of mice with a trivalent seasonal influenza vaccine elicited heterosubtype H5-reactive antibodies able to confer partial protection against H5N1 influenza virus infection. Furthermore, the trivalent seasonal influenza vaccine was found to be compatible with a whole virus H5N1 vaccine in a heterologous prime-boost immunization regimen, achieving superior efficacy compared to a single immunization with an equivalent low-dose of the H5N1 vaccine.     

Soliciting views of various communities on health research: a prelude to engagement in specific research projects

BackgroundMembers of the public are increasingly engaged in health‐service and biomedical research and provide input into the content of research, design and data sharing. As there is variation among different communities on how research is perceived, to engage all sectors of the general public research institutions need to customize their approach.ObjectiveThis paper explores how research institutions and community leaders can partner to determine the best ways to engage different sectors of the public in research.DesignFollowing a literature review, a research institution engaged with four different sectors of the public through their respective representative community‐based organizations (CBOs) by interviews with leaders, community member focus groups and a joint project.SettingSan Diego and Imperial Counties, California, United States of America (USA).ConclusionBefore embarking on more specific research projects, investigators can gain valuable insights about different communities'' attitudes to, and understanding of, health services and biomedical research by interacting directly with members of the community, collaborating with community leaders, and jointly identifying steps of engagement tailored to the community.     

Cell culture (Vero) derived whole virus (H5N1) vaccine based on wild-type virus strain induces cross-protective immune responses

The rapid spread and the transmission to humans of avian influenza virus (H5N1) have induced world-wide fears of a new pandemic and raised concerns over the ability of standard influenza vaccine production methods to rapidly supply sufficient amounts of an effective vaccine. We report here on a robust and flexible strategy which uses wild-type virus grown in a continuous cell culture (Vero) system to produce an inactivated whole virus vaccine. Candidate vaccines based on clade 1 and clade 2 influenza H5N1 strains were developed and demonstrated to be highly immunogenic in animal models. The vaccines induce cross-neutralising antibodies, highly cross-reactive T-cell responses and are protective in a mouse challenge model not only against the homologous virus but also against other H5N1 strains, including those from another clade. These data indicate that cell culture-grown whole virus vaccines, based on the wild-type virus, allow the rapid high yield production of a candidate pandemic vaccine.     

Prevalence and correlates of mental disorders among Native American women in primary care

OBJECTIVES: We examined the lifetime and the past-year prevalence and correlates of common mental disorders among American Indian and Alaska Native women who presented for primary care. METHODS: We screened 489 consecutively presenting female primary care patients aged 18 through 45 years with the General Health Questionnaire, 12-item version. A subsample (n = 234) completed the Composite International Diagnostic Interview. We examined associations between psychiatric disorders and sociodemographic variables, boarding school attendance, and psychopathology in the family of origin. RESULTS: The study participants had high rates of alcohol use disorders, anxiety disorders, and anxiety/depression comorbidity compared with other samples of non-American Indian/Alaska Native women in primary care settings. CONCLUSIONS: There is a need for culturally appropriate mental health treatments and preventive services.     

Malaria mosquito control using edible fish in western Kenya: preliminary findings of a controlled study

Background  

Biological control methods are once again being given much research focus for malaria vector control. This is largely due to the emerging threat of strong resistance to pesticides. Larvivorous fish have been used for over 100 years in mosquito control and many species have proved effective. In the western Kenyan highlands the larvivorous fish Oreochromis niloticus L. (Perciformes: Cichlidae) (formerly Tilapia nilotica) is commonly farmed and eaten but has not been previously tested in the field for malaria mosquito control.