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PubMed1983

Longitudinal study of asymptomatic meningococcal carriage in two Belgian populations of schoolchildren.

In Brussels, a 15-month longitudinal survey was conducted in two primary schools, from March 1975 to May 1976, in order to analyse the dynamic of asymptomatic meningococcal carriage, during an epidemic mainly caused by serogroup B, serotype 2 Neisseria meningitidis. In the first school, which is situated in a suburban area with upper-middle socio-economic status of residents, a mean prevalence of carriers of 10 per cent, an acquisition rate of eight per 1000 months, and a mean duration of carriage of 12.4 months were observed among 158 schoolchildren aged six to 11 years old. In the second school, which is situated in a densely populated area with low socio-economic status of residents, a mean prevalence of carriers of 33 per cent, an acquisition rate of 28 per 1000 months, and a mean duration of carriage of 11.7 months were observed among 203 schoolchildren aged three to 14 years old. For both schools, the median duration of carriage was estimated at 9.4 months. The differences of prevalence and incidence of acquisition between the two schools cannot be explained by age, sex or ethnic factors and are probably related to socio familial variables. The theoretical relationship between prevalence, incidence and duration of meningococcal carriage was for the first time demonstrated in this study. The results also suggest that populations of low socio-economic status and living in densely populated areas constitute a target population for meningococcal disease prevention.

Adolescent↗
PubMed2003

Medicinal chemistry of target family-directed masterkeys.

The majority of pharmaceutically relevant drug targets cluster into densely populated target families, thus offering a novel approach that complements the currently favoured screening paradigm in medicinal chemistry. This approach uses a privileged structure concept whereby molecular masterkeys are developed that account for a target family wide structural or functional commonality. Numerous lead compounds, based on multipurpose privileged structures, can be generated that address a variety of targets from a gene family of interest, irrespective of therapeutic area. Several different interpretations of the privileged structure concept will be highlighted, with a strong emphasis on the most stringent application: the optimization of a molecular masterkey for a distinct target family of interest.

Animals↗
PubMed2003

The case for domains of function in quality of life assessment.

Over the past 20 years, there has been a growing interest in the inclusion of health-related quality of life (HRQL) measures to assess the effects of a condition and/or its therapies on a person's health. In response to this interest, methods to assess health status and HRQL have proliferated. There are now a number of valid and reliable instruments available for use in research investigations, which are the culmination of years of research with various populations, and reflect the target populations' perceptions of their health status and HRQL. In this article, we provide a definition of HRQL and its dimensions; describe types of HRQL instruments; discuss variations in how HRQL measures are scored and how these methods influence the interpretation of results; briefly describe utility measures; and summarize by discussing basic issues in the selection of HRQL instruments for research investigations.

Adaptation, Psychological↗
PubMedDate not supplied

Broadening the base of a rare donor program by targeting minority populations.

Some red cell phenotypes are found exclusively in one race and may be of low frequency. Finding compatible blood for patients needing one of these rare types has been extremely difficult. A program was implemented to screen large numbers of donors for blood types found solely in their racial group. Implementation steps included obtaining broad community endorsement of the concept, educating blood service personnel, developing educational materials, enlisting the support of a knowledgeable physician from a minority group, developing a computer program to facilitate selection of donors to be tested, beginning the program and making the necessary adjustments, doing the laboratory testing to identify rare bloods, notifying the rare donors, and maintaining the enthusiasm of the entire blood service for the rare donor screening program. After 7706 black donors were typed, 1 Cr-, 5 Hy-, 24 U-, and 20 Js(b-) persons were found; one U- donor was also Js(b-).

Black People↗
PubMed2000

Activation of divergent neuronal cell death pathways in different target cell populations during neuroadapted sindbis virus infection of mice.

Infection of adult mice with neuroadapted Sindbis virus (NSV) results in a severe encephalomyelitis accompanied by prominent hindlimb paralysis. We find that the onset of paralysis parallels morphologic changes in motor neuron cell bodies in the lumbar spinal cord and in motor neuron axons in ventral nerve roots, many of which are eventually lost over time. However, unlike NSV-induced neuronal cell death found in the brain of infected animals, the loss of motor neurons does not appear to be apoptotic, as judged by morphologic and biochemical criteria. This may be explained in part by the lack of detectable caspase-3 expression in these cells.

Adaptation, Physiological↗
PubMed2004

Population genetics of autocidal control and strain replacement.

The concept that an insect species' genome could be altered in a manner that would result in the control of that species (i.e., autocidal control) or in the replacement of a pestiferous strain of the species with a more benign genotype was first proposed in the mid-twentieth century. A major research effort in population genetics and ecology followed and led to the development of a set of classical genetic control approaches that included use of sterile males, conditional lethal genes, translocations, compound chromosomes, and microbe-mediated infertility. Although there have been a number of major successes in application of classical genetic control, research in this area has declined in the past 20 years for technical and societal reasons. Recent advances in molecular biology and transgenesis research have renewed interest in genetically based control methods because these advances may remove some major technical problems that have constrained effective genetic manipulation of pest species. Population genetic analyses suggest that transgenic manipulations may enable development of strains that would be 10 to over 100 times more efficient than strains developed by classical methods. Some of the proposed molecular approaches to genetic control involve modifications of classical approaches such as conditional lethality, whereas others are novel. Experience from the classical era of genetic control research indicates that the population structure and population dynamics of the target population will determine which, if any, genetic control approaches would be appropriate for addressing a specific problem. As such, there continues to be a need for ongoing communication between scientists who are developing strains and those who study the native pest populations.

Animals↗
PubMedDate not supplied

The nongenotoxic hepatocarcinogens diethylhexylphthalate and methylclofenapate induce DNA synthesis preferentially in octoploid rat hepatocytes.

Diethylhexylphthalate (DEHP), a rodent carcinogen, and 1,4-dichlorobenzene (DCB), a noncarcinogen in rat liver, are potent hepatomitogens. We have reported previously that 7-day dosing with DEHP induced a higher bromodeoxyuridine labeling index (LI) in binuclear octoploid (2x4N) rat hepatocytes than did DCB, suggesting that induction of DNA synthesis in 2x4N hepatocytes might represent a more substantial carcinogenic risk. We compared 2 additional rodent hepatocarcinogens, methylclofenapate (MCP) and phenobarbitone, with ethylene thiourea (ETU), a noncarcinogenic hepatomitogen in rat. All 3 chemicals increased hepatic LI; the 8N population had the highest LI, but only the carcinogens increased LI in the 2x4N and 4N populations. To identify the target population for induction of DNA synthesis, we used a 1-hour pulse label at the peak of induction. The results were consistent with the 7-day data, and again the highest LI was in the 8N population. The nongenotoxic rodent carcinogens MCP and DEHP induced a significant increase in the LI in the 2x4N population, whereas ETU and DCB did not. These data support the hypothesis that increased DNA synthesis within the minority 2x4N population may be more significant for subsequent hepatocarcinogenesis.

Animals↗
PubMed2006

In vivo response-based identification of direct hormone target cell populations using high-density tissue arrays.

To identify cell populations directly responsive to prolactin (PRL), GH, erythropoietin, or granulocyte-colony stimulating factor within the physiological setting of an intact mammal, we combined in situ detection of hormone-activated signal transducer and activator of transcription (Stat)-5 in rats with high-throughput tissue array analysis using cutting-edge matrix assembly (CEMA). Inducible activation of Stat5a/b, as judged by levels of nuclear-localized, phosphoTyr694/699-Stat5a/b, served as an immediate and sensitive in situ marker of receptor signaling in rat tissues after injection into male and female rats of a single, receptor-saturating dose of hormone for maximal receptor activation. CEMA tissue arrays facilitated analysis of most tissues, including architecturally complex, thin-walled, and stratified tissues such as gut and skin. In 40 tissues analyzed, 35 PRL-responsive and 32 GH-responsive cell types were detected, of which 22 cell types were responsive to both hormones. Interestingly, PRL but not GH activated Stat5 in nearly all of the endocrine glands. In mammary glands, PRL activated Stat5 in a majority of luminal epithelial cells but not myoepithelial cells, stromal fibroblasts, or adipocytes, whereas GH activated Stat5 in a significant fraction of myoepithelial cells, fibroblasts, and adipocytes but only in a minority of luminal cells. Finally, the organism-wide screening revealed a yet-to-be identified erythropoietin-responsive cell type in connective tissue. CEMA tissue arrays provide cost-effective in situ analysis of large numbers of tissues. Biomarker-based identification of cell populations responsive to individual hormones may shed new light on endocrine disease as well as improve understanding of effects and side effects of hormones and drugs.

Animals↗
PubMed1995

Targeting Hispanic populations: future research and prevention strategies.

Minority populations face a wide variety of economic, institutional, and cultural barriers to health care. These barriers and low levels of education and income pose significant challenges for health professionals in developing cancer research and prevention-control strategies. It is suggested that specific segments of Hispanic populations fit the model of an underdeveloped country in the intermediate stage of epidemiological transition. Since noncommunicable diseases have not yet fully emerged in some of these Hispanic population segments, the opportunity exists to apply primordial prevention strategies. Such campaigns would focus on dissuading members of these populations from adopting negative health behaviors while promoting positive lifestyle choices. Optimal programs would increase cancer screening participation and discourage risk behaviors through community-oriented, population-based interventions. Future directions in prevention and control efforts for minority populations should include expanded health insurance coverage, improved access to health care, greater emphasis on minority recruitment in health care fields, focused epidemiologic and clinical research, and identification and replication of effective components within existing prevention-control programs.

Delivery of Health Care↗
PubMed2004

Long-term controlled field experiment on the competition between two species of Biomphalaria (Mollusca, Basommatophora), the snail vectors of Schistosoma mansoni in Northeastern Brazil.

A long-term controlled field experiment on the interactions of the populations of Biomphalaria glabrata (target population) and B. straminea (competitor) was carried out in the county of Alhandra, state of Paraíba, Brazil, during the period 1980 through 1989. Results obtained in the current paper show that the snail B. straminea has strong competitive advantages over B. glabrata. In six out of nine streams the native population of B. glabrata were totally excluded and replaced by B. straminea. There is evidence showing that seasonal dryness has marked influence on the phenomenon studied in this paper. In all the streams were B. straminea already predominated, return of B. glabrata was never observed.

Journal Article↗
PubMed2004

"Virostatics" as a potential new class of HIV drugs.

The combination of three or more antiretroviral drugs is referred to as highly active antiretroviral therapy (HAART) and constitutes the standard of care for HIV-1 patients in industrialized nations. Although HAART is usually effective in reducing viral load and re-constituting CD4 counts, latent virus reservoirs persist, and as many as 60 years therapy [1, 2] may be required to eradicate the virus. Meanwhile, patients are likely to experience drug related toxicity and may have to change therapy due to the emergence of drug resistant strains. For these reasons, the search for different therapeutic approaches continues. A new concept of antiviral/cytostatic ("virostatics") drugs has been proposed within the context of HAART to restrict virus target populations (CD4(+) T lymphocytes), target viral reservoirs, and possibly restore immune functions, by reducing excess immune activation, a fundamental component of HIV/AIDS pathogenesis. These virostatics include drugs such as hydroxyurea, mycophenolic acid, leflunomide and rapamycin, which are currently used for other therapeutic indications; and other experimental drugs, which are not for human use. They utilize multiple novel mechanisms of action to impede HIV by targeting host cellular proteins that are not susceptible to mutation. Therefore, their resistance profile appears to be quite favorable. Since many of these drugs act by inhibiting the synthesis of deoxynucleotides, essential for HIV reverse transcription, they favor the incorporation of nucleoside analogues into viral DNA, thus synergizing with the antiviral activity of currently used nucleoside reverse transcriptase inhibitors (NRTI). The rationale for the use of virostatics in HIV/AIDS, their mechanism of action, and ongoing preclinical and clinical research will be reviewed.

Animals↗
PubMed2006

Invasive pneumococcal disease in Australia, 2004.

There were 2,375 cases of invasive pneumococcal disease (IPD) notified to the National Notifiable Diseases Surveillance System in Australia in 2004; a notification rate of 11.8 cases per 100,000 population. The rate varied between states and territories and by geographical region with the highest rates in the Northern Territory. Invasive pneumococcal disease was reported most frequently in children aged less than 5 years (55.4 cases per 100,000 population). Enhanced surveillance for IPD was carried out in all states and territories, in 2004, providing additional data on 2,023 (85%) cases. The overall rate of IPD in Indigenous Australians was 3.2 times the rate in non-Indigenous Australians. There were 154 deaths attributed to IPD resulting in an overall case fatality rate of 7.6 per cent. Rates of IPD in the Indigenous and non-Indigenous under 2-year-old population were similar in 2004 (91.5 and 93.6 cases per 100,000 population, respectively) following a targeted introduction of the 7-valent pneumococcal conjugate vaccine (7vPCV) in mid-2001 for Indigenous infants and children. Serotypes of isolates were identified from 80 per cent of all notified cases, with 72 per cent of isolates belonging to serotypes represented in the 7vPCV and 91 per cent in the 23-valent polysaccharide pneumococcal vaccine (23vPPV). Comparison of serotypes in the 7vPCV target population showed that the rate of IPD due to 7vPCV serotypes decreased by 74 per cent between 2001-02 and 2003-04. Of 216 isolates with reduced penicillin susceptibility, 83 per cent belonged to pneumococcal serotypes in the 7vPCV and 95 per cent in the 23vPPV.

Adolescent↗