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PubMed1996

Virulence as a positive trait in viral persistence.

A population replacement experiment has been devised to test the ability of a challenge virus to replace the resident virus in a persistently infected cell culture. BHK-21 cells persistently infected with foot-and-mouth disease virus of serotype C (clone C-S8c1) were challenged with a large excess of either the parental foot-and-mouth disease virus C-S8c1, genetically marked variants differing in their degree of virulence, or a mutant rescued after prolonged persistence in BHK-21 cells. After challenge, the composition of the resident virus population in the carrier culture was analyzed by reverse transcription-PCR amplification and nucleotide sequencing. The dominance of the initial persisting virus was seen in all cases, except when virulent viruses were used in the challenge. The experiments document that, paradoxically, virulence can be a positive factor in the reestablishment of a virus population in a persistently infected cell culture. A model based on the selection of virus-resistant cell variants during persistence is proposed to interpret these observations. Implications about the persistence of viruses in their host cells and organisms are discussed.

Animals↗
PubMed1994

Thoracic aortic aneurysmectomy with a sutureless intraluminal ringed graft.

Forty-two patients underwent replacement of the thoracic aorta with a sutureless intraluminal graft. Early and long-term results were evaluated. The operative mortality rate was 7.1%. There were two postoperative complications related to a ringed graft. One complication, the formation of a pseudoaneurysm, was caused by insufficient fixation of the graft; the other, a cerebral infarction, was related to the location of the proximal anastomosis with respect to the origin of the left subclavian artery. The 3- and 5-year actuarial survival rates were 86 and 69.5%, respectively. These were similar to survival rates of age-matched controls in the general Japanese population. Replacement of the thoracic aorta using a sutureless intraluminal graft can be performed with acceptable operative mortality, with good long-term results.

Adult↗
PubMed1984

Comparative protective actions of gonadotrophins and testosterone against the antispermatogenic action of ethane dimethanesulphonate.

After a single dose of ethane dimethanesulphonate (EDS) (75 mg/kg) to rats the prolonged antispermatogenic action is due to a temporary elimination of the functional Leydig cell population. Replacement therapy with testosterone propionate (3 mg/day) maintains the spermatogenic epithelium but the EDS effect develops when hormone treatment is discontinued. In contrast, a short treatment with hCG (10-100 i.u./day) or LH (714 micrograms/day), starting before the EDS dose, permanently protects the spermatogenic epithelium. FSH treatment was completely ineffective. Although histological protection of spermatogenesis appeared complete with testosterone or hCG, effects on fertility remained but over different periods of time. Antispermatogenic and antifertility effects were produced in mice using much higher doses of EDS (5 X 250 mg/kg) but there was no protection from androgen or hCG. It is suggested that EDS binds to Leydig cells irreversibly, interfering with the action of gonadotrophin. At the dose level used the evidence suggests that the degree of reaction renders most of the Leydig cell population non-viable. A direct cytotoxic effect of the compound upon the spermatogenic epithelium might account for the inability of testosterone or hCG alone or in combination to maintain fertility at normal levels.

Animals↗
PubMed2002

[The capture-recapture applied to epidemiology: principles, limits and application].

By matching several sources of information coming from the same population, the capture-recapture method allows, if matches between sources can be identified, to estimate the number of cases not identified by any of the sources, the total number (N) of cases in the population and the sensitivity of each source. Used first in zoology and demography, this technique has been increasingly applied to epidemiology in the last two decades. However, six conditions need to be satisfied: all cases identified by each source are true cases; occurred during the time and the geographical area studied; the study population is closed; all matches are true matches; sources are independent and there is no heterogeneous catchability within sources. It is possible to assess and take into account dependence between sources when 3 or more sources are used, in particular by log linear modelling. However interactions of maximal order cannot be adjusted for. In case of a biased estimation because of the non respect of the conditions, it is recommended to apply a method of correction. The complete application of the methods is illustrated in the study of estimating the number of Salmonella infectious foodborne outbreak. As capture-recapture studies often use data collected for other purposes, this technique should be regarded as exploratory or be used to validate an estimate of a number of cases obtained by another method. It should not replace population sampling methods only because of its low cost. Otherwise it is a very informative approach to evaluate the sensitivity and representativeness of surveillance systems and registries.

Algorithms↗
PubMed2004

It's time to retire. Retirement.

Companies have been so focused on down-sizing to contain costs that they've largely neglected a looming threat to their competitiveness: a severe shortage of talented workers. The general population is aging and with it, the labor pool. People are living longer, healthier lives, and the birthrate is at a historical low. During the next 15 years, 80% of the native-born workforce growth in North America--and even more in much of Western Europe--is going to be in the over-50 age cohort. When these mature workers begin to retire, there won't be nearly enough young people entering the workforce to compensate. The Bureau of Labor Statistics projects a shortfall of 10 million workers in the United States in 2010, and in countries where the birthrate is well below the population replacement level (particularly in Western Europe), the shortage will hit sooner, be more severe, and remain chronic. The problem won't just be a lack of bodies. Skills, knowledge, experience, and relationships walk out the door every time somebody retires--and they take time and money to replace. And while the brain drain is beginning now, the problem is going to become much more acute in the next decade or so, when baby boomers--more than one-quarter of all Americans, amounting to 76 million people--start hitting their mid sixties. Based on the results of their yearlong research project, the authors of this article offer recommendations for gaining the loyalty of older workers and creating a more flexible approach to retirement that allows people to continue contributing well into their sixties and seventies. Companies can no longer afford to think of retirement as a onetime event, permanently dividing work life from leisure.

Aged↗
PubMed1984

Kinetic differences between fed and starved Chinese hamster ovary cells.

When Chinese hamster (CHO-K1) cells are grown as monolayer cultures, they eventually reach a population-density plateau after which no net increase in cell numbers occurs. The kinetics of aged cells in nutritionally deprived (starved) or density-inhibited (fed) late plateau-phase cultures were studied by four methods: (i) Reproductive integrity and cell viability were monitored daily by clonogenic-cell assay and erythrosin-b dye-exclusion techniques. (ii) Mitotic frequencies of cells from 18 day old cultures were determined during regrowth by analysing time-lapse video microscope records of dividing cells. (iii) Tritiated-thymidine ([3H]TdR) autoradiography was used to determine the fractions of DNA-synthesizing cells in cultures entering plateau phase and during regrowth after harvest. (iv) The rate of labelled nucleoside uptake and incorporation into DNA was measured using liquid scintillation or sodium iodide crystal counters after labelling with [3H]TdR or [125I]UdR. Non-cycling cells in starved cultures accumulate primarily as G1 phase cells. Most cells not in G1 phase had stopped in G2 phase. Very few cells (less than 2%) were found in S phase. In contrast, about half of the cells in periodically fed cultures were found to be in DNA-synthetic phase, and the percentage of these S phase cells fluctuated in a manner reflecting the frequency of medium replacement. Populations of both types of plateau-phase cultures demonstrate extremely coherent cyclic patterns of DNA synthesis upon harvest and reculturing. They retain this high degree of synchrony for more than three generations after the resumption of growth. From these data it is concluded that nutritionally deprived (starved) late plateau-phase cells generally stop in either G1 or G2 phase, whereas periodically fed late plateau-phase cultures contain a very large fraction of cycling cells. Populations of cells from these two types of non-expanding cultures are kinetically dissimilar, and should not be expected to respond to extracellular stimuli in the same manner.

Animals↗
PubMed2004

A hypothetical anti-neoplastic mechanism associated to reserve cells.

Reserve-stem cells, the permanent cells of body tissues, are thought to be the progenitor cells of cancer. This concept originates from the assumption that accumulation of somatic mutations necessary for malignant transformation can only take place in cellular targets with a prolonged life span. The progeny of reserve cells entering the differentiative pathway would be protected from potential critical mutations happening later than the reserve cell stage by normal cell population replacement unless possible targets would escape the replacement process by further mutations extending the cell's life span, impairment of physiological apoptosis. The existence of a mechanism for maintenance of genetic integrity in stem/reserve cells has previously been proposed. This mechanism differs from already identified DNA repair systems and, potentially, could prevent malignant transformation at the reserve cell stage, counteracting the expected high propensity of stem/reserve cells to neoplastic proliferation. Here, we show some histopathological observations suggesting that an anti-cancer mechanism might be associated to reserve/stem cells and that it could be responsible for huge differences in cancer incidence between closely related body sites. Furthermore, primary impairment of this protective mechanism might characterize the oncogenic pathway responsible for tumors of primitive cells. Several features of the histopathological observations presented lead us to propose that the underlying molecular mechanism may involve the telomere complex.

Animals↗
PubMed1998

Estrogens and postprandial lipid metabolism.

Women with angiographically proven coronary heart disease (CAD) had higher postprandial concentrations of small chylomicron-remnants, measured as IDL apo B48, than women without CAD. Fasting TG concentrations were not different and within the normal range. Thus, the postprandial concentration of small chylomicron-remnants could identify women at high CAD risk within a normolipidemic population. Replacement therapy with 17beta-estradiol improved the clearance of chylomicron-remnants by 41% and attenuated the postprandial reduction in HDL-cholesterol by 66%. This improvement in postprandial lipid metabolism can explain part of the protective effect of estrogens against CAD.

Adult↗
PubMed2002

Improving iron, zinc and vitamin A nutrition through plant biotechnology.

Recent understanding of plant metabolism has made it possible to increase the iron, zinc and beta-carotene (provitamin A) content in staple foods by both conventional plant breeding and genetic engineering. Improving the micronutrient composition of plant foods may become a sustainable strategy to combat deficiencies in human populations, replacing or complementing other strategies such as food fortification or nutrient supplementation.

Anemia, Iron-Deficiency↗
PubMed2005

An alternative to Cohen's standardized mean difference effect size: a robust parameter and confidence interval in the two independent groups case.

The authors argue that a robust version of Cohen's effect size constructed by replacing population means with 20% trimmed means and the population standard deviation with the square root of a 20% Winsorized variance is a better measure of population separation than is Cohen's effect size. The authors investigated coverage probability for confidence intervals for the new effect size measure. The confidence intervals were constructed by using the noncentral t distribution and the percentile bootstrap. Over the range of distributions and effect sizes investigated in the study, coverage probability was better for the percentile bootstrap confidence interval.

Analysis of Variance↗
PubMed2003

Superinfection of Laodelphax striatellus with Wolbachia from Drosophila simulans.

Wolbachia are maternally inherited, intracellular alpha-proteobacteria that infect a wide range of arthropods. They manipulate the reproduction of hosts to facilitate their spread into host populations, through ways such as cytoplasmic incompatibility (CI), parthenogenesis, feminization and male killing. The influence of Wolbachia infection on host populations has attracted considerable interest in their possible role in speciation and as a potential agent of biological control. In this study, we used both microinjection and nested PCR to show that the Wolbachia naturally infecting Drosophila simulans can be transferred into a naturally Wolbachia-infected strain of the small brown planthopper Laodelphax striatellus, with up to 30% superinfection frequency in the F(12) generation. The superinfected males of L. striatellus showed unidirectional CI when mated with the original single-infected females, while superinfected females of L. striatellus were compatible with superinfected or single-infected males. These results are, to our knowledge, the first to establish a superinfected horizontal transfer route for Wolbachia between phylogenetically distant insects. The segregation of Wolbachia from superinfected L. striatellus was observed during the spreading process, which suggests that Wolbachia could adapt to a phylogenetically distant host with increased infection frequency in the new host population; however, it would take a long time to establish a high-frequency superinfection line. This study implies a novel way to generate insect lines capable of driving desired genes into Wolbachia-infected populations to start population replacement.

Animals↗
PubMed2006

Engineering RNA interference-based resistance to dengue virus type 2 in genetically modified Aedes aegypti.

Mosquitoes (Aedes aegypti) were genetically modified to exhibit impaired vector competence for dengue type 2 viruses (DENV-2). We exploited the natural antiviral RNA interference (RNAi) pathway in the mosquito midgut by constructing an effector gene that expresses an inverted-repeat (IR) RNA derived from the premembrane protein coding region of the DENV-2 RNA genome. The A. aegypti carboxypeptidase A promoter was used to express the IR RNA in midgut epithelial cells after ingestion of a bloodmeal. The promoter and effector gene were inserted into the genome of a white-eye Puerto Rico Rexville D (Higgs' white eye) strain by using the nonautonomous mariner MosI transformation system. A transgenic family, Carb77, expressed IR RNA in the midgut after a bloodmeal. Carb77 mosquitoes ingesting an artificial bloodmeal containing DENV-2 exhibited marked reduction of viral envelope antigen in midguts and salivary glands after infection. DENV-2 titration of individual mosquitoes showed that most Carb77 mosquitoes poorly supported virus replication. Transmission in vitro of virus from the Carb77 line was significantly diminished when compared to control mosquitoes. The presence of DENV-2-derived siRNAs in RNA extracts from midguts of Carb77 and the loss of the resistance phenotype when the RNAi pathway was interrupted proved that DENV-2 resistance was caused by a RNAi response. Engineering of transgenic A. aegypti that show a high level of resistance against DENV-2 provides a powerful tool for developing population replacement strategies to control transmission of dengue viruses.

Aedes↗
PubMed1974

The pertinence of the periodic selection phenomenon to prokaryote evolution.

A quarter of a century ago, it was pointed out that evolution can act in an important conservative way, in addition to its normal progressive mode. Evolution to a fitter form via changes at one locus means that the descendants of an individual with an improved locus or set of loci will supplant the previous population and carry with them the bulk of the total genotype of that original individual in asexual populations. Inasmuch as that individual is most likely to be wild type at most other loci, neutral and even other positively selected mutations will be reduced or eliminated from the population, if they are rare at the time of the evolutionary advance. In the present paper this problem has been set up for a computer simulation. The computations show the limits within which this effect functions and the conditions under which it does not. The conclusion is that it is likely that evolution at a locus proceeds in the course of many population replacements or revolutions, mostly via the rare occasions when the revolution carries a previously infrequent mutational type into abundance.

Biological Evolution↗
PubMed2005

The origins of Iberian horses assessed via mitochondrial DNA.

Despite a number of recent studies that have focused on the origin of domestic horses, genetic relationships between major geographical clusters still remain poorly understood. In this study we analyzed a 296 bp mtDNA fragment from the HVI region of 171 horses representing 11 native Iberian, Barb, and Exmoor breeds to assess the maternal phylogeography of Iberian horses. The mtDNA haplogroup with a CCG motif (nucleotide position 15,494 to 15,496) was the most frequent in Iberian and Barb breeds (0.42 and 0.57, respectively), regardless of geographic location or group of breeds. This finding supports the close genetic relationship between the ancestral mare populations of the Iberian Peninsula and Northern Africa. Phenotypic differences among the Northern and Southern Iberian groups of breeds are not explained by population subdivision based on maternal lineages. Our results also suggest that Northern Iberian ponies--which are phenotypically close to British ponies, especially Exmoor--are the result of an introgression rather than population replacement.

Animals↗
PubMedDate not supplied

Integrating patient care delivery.

Concepts of coordinated care, case management, and continuous quality improvement were applied by a medical center nursing service to improve continuity and coordination of patient care between inpatient and outpatient programs. Quality and cost outcomes are presented for a pilot project with a total hip replacement population.

Clinical Protocols↗
PubMed1991

Psychological development at 7 years of age in children with congenital hypothyroidism. Timing and dosage of initial treatment.

Sixty of 68 consecutive patients detected during the first two years of the Swedish screening programme for congenital hypothyroidism were Griffiths tested at the age 6.5-7.5 years. The test quotients of the patients could not be distinguished from those of a reference population. Replacement therapy with 8.7 +/- 2.8 micrograms of L-thyroxine (mean +/- SD)/kg/d had been started at 15.0 +/- 7.1 days of life. Furthermore, normal results on Griffiths tests were also found in 13 patients with delayed normalization of serum TSH, i.e. greater than 19 mU/l at the age of six weeks, as well as in patients with retarded skeletal maturity and/or very low neonatal serum levels of thyroxine, i.e. less than 18 nmol/l and tri-iodothyronine, i.e. less than 0.92 nmol/l. Our findings indicate that a replacement dose of 6-11 micrograms L-thyroxine/kg/d is adequate and allows normal psychological development if treatment is started early.

Bone Development↗
PubMed1995

Turnover of circulating virion RNA and of cell-associated viral DNA reflects active viral replication in human immunodeficiency virus type 1-infected individuals.

A quantitative assessment of human immunodeficiency virus type 1 turnover in patient cell-free virion and infected-cell compartments under the dynamic conditions imposed by an effective antiviral therapy was performed. The turnover was rapid, and following a temporal lag, the extent of viral population replacement was eventually similar in both compartments. Each compartment therefore reflects considerable active virus replication.

Antiviral Agents↗