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Oculocutaneous albinism in an isolated Tonga community in Zimbabwe.

Oculocutaneous albinism (OCA) is a recessively inherited genetic condition prevalent throughout sub-Saharan Africa. We now describe a cluster of tyrosinase positive OCA (OCA2) cases belonging to the Tonga ethnic group living in the Zambezi valley of northern Zimbabwe. The prevalence in this region was 1 in 1000, which is four times higher than that for the country as a whole. The gene frequency for OCA2 in this population was calculated as 0.0316, with a carrier rate of 1 in 16. Molecular analysis showed that all five affected subjects from two independent families examined were found to be homozygous for an interstitial 2.7 kb deletion mutation commonly found in OCA2 subjects in Africa. An obligate carrier from another family was heterozygous for this deletion allele. Affected subjects in this isolated community suffered health, social, and economic problems.

Adolescent↗

High diversity of the chicken growth hormone gene and effects on growth and carcass traits.

The chicken growth hormone (cGH) gene plays a crucial role in controlling growth and metabolism, leading to potential correlations between cGH polymorphisms and economic traits. In this study, DNA from four divergent chicken breeds were screened for single nucleotide polymorphisms (SNPs) in the cGH gene using denaturing high-performance liquid chromatography and sequencing. A total of 46 SNPs were identified, of which 4 were in the 5' untranslated region, 1 in the 3' untranslated region, 5 in exons (two of which are nonsynonymous), with the remaining 36 in introns. The nucleotide diversity in the cGH gene ( theta = 2.7 x 10(-3)) was higher than that reported for other chicken genes, even within the same breeds. The associations of five of these SNPs and their haplotypes with chicken growth and carcass traits were determined using polymerase chain reaction-restriction fragment length polymorphism analysis in a F2 resource population cross of two of the four chicken breeds (White Recessive Rock and Xinghua). This analysis shows that, among other correlations, G+1705A was significantly associated with body weight at all ages measured, shank length at three of four ages measured, and average daily gain within weeks 0 to 4. Thus, this cGH polymorphism, or another polymorphism that is in linkage disequilibrium with G+1705A, appears to correspond to a significant growth-related quantitative trait locus difference between the two breeds used to construct the resource population.

Animals↗

Variations in ploidy among isolates of Botrytis cinerea: implications for genetic and molecular analyses.

Field isolates and laboratory strains of Botrytis cinerea, an ascomycetous fungus causing considerable economic losses, e.g., as "grey mould" of vine, were compared for differences in ploidy level by determining their DNA content per nucleus. Strain SAS56, an ascospore line used routinely for genetic analyses, is probably polyploid, since treatment with benomyl causes a significant reduction in DNA content per nucleus. This conclusion is substantiated by the increased sensitivity of the putative haploid derivatives to mutagens (UV and EMS). Molecular analyses (RAPD) of the haploidized strains indicate a very limited degree of heterozygosis of the parent strain SAS56. Analysis of field isolates of B. cinerea showed that their DNA content per nucleus varied considerably, indicating that aneuploidy/polyploidy is a widespread phenomenon in this species. This can explain both the variability and phenotypic instability of many field isolates of this fungus and the unusual difficulties faced by researchers in recovering stable recessive laboratory mutants. Since the haploid derivatives of SAS56 resemble the parent strain in their parasitic and physiological properties they should provide a good basis for classical and molecular genetic studies.

Base Sequence↗

QTL fine mapping by measuring and testing for Hardy-Weinberg and linkage disequilibrium at a series of linked marker loci in extreme samples of populations.

It has recently been demonstrated that fine-scale mapping of a susceptibility locus for a complex disease can be accomplished on the basis of deviations from Hardy-Weinberg (HW) equilibrium at closely linked marker loci among affected individuals. We extend this theory to fine-scale localization of a quantitative-trait locus (QTL) from extreme individuals in populations, by means of HW and linkage-disequilibrium (LD) analyses. QTL mapping and/or linkage analyses can establish a large genomic region ( approximately 30 cM) that contains a QTL. The QTL can be fine mapped by examination of the degree of deviation from HW and LD at a series of closely linked marker loci. The tests can be performed for samples of individuals belonging to either high or low percentiles of the phenotype distribution or for combined samples of these extreme individuals. The statistical properties (the power and the size) of the tests of this fine-mapping approach are investigated and are compared extensively, under various genetic models and parameters for the QTL and marker loci. On the basis of the results, a two-stage procedure that uses extreme samples and different tests (for HW and LD) is suggested for QTL fine mapping. This two-step procedure is economic and powerful and can accurately narrow a genomic region containing a QTL from approximately 30-1 cM, a range that renders physical mapping feasible for identification of the QTL. In addition, the relationship between parameterizations of complex diseases, by means of penetrance, and those of complex quantitative traits, by means of genotypic values, is outlined. This means that many statistical genetic methods developed for searching for susceptibility loci of complex diseases can be directly adopted and/or extended to QTL mapping for quantitative traits.

Alleles↗

Relationship between prosthodontic status, caries, and periodontal disease in a geriatric population.

This study evaluated the influence of prosthodontic status on caries a and periodontal disease in a hospitalized population of elderly people. Among the data gathered was information on caries, gingival condition, oral hygiene, plaque accumulation, and factors related to the prevalence, type and quality of the prostheses present. There was no significant association between the type of rehabilitation and the economic, social, or educational variables, but it appeared that removable partial denture wearers had less concern for oral health. Root caries and periodontal diseases were more frequent when the restoration, either fixed or removable, was defective. Th results of this study indicate the importance of oral hygiene instruction and regular recalls among removable partial denture wearers.

Aged↗

Choices in Dutch health care: mixing strategies and responsibilities.

In the light of experience that choices in health care appear to be not so much hindered by a lack of insight into how choices should be made in theory, as uncertainty as to how choices could be made in practice, this paper sets out to deepen our insight into the dynamics of health care policy making within the concrete socio-economic and political context. The paper examines how Dutch policy-makers have dealt with the priority issue in health care over the past 10 years by means of a gradual incremental approach. In this approach, use is made of a mix of strategies and shared responsibilities, with an important role for the actors at the meso and the micro levels; while at the same time, the government has not abandoned the tried and trusted policy of national rationing (i.e. keeping the production capacity limited and setting a ceiling on production in order to resist the pressure on the public system of Dutch health care). Looking at the declining percentage of Gross National Product assigned to health care annually, the broad accessibility and the good overall quality of Dutch health care, it may be concluded that the issue of choice has not come off badly under this mixed approach. The degree to which the system can respond adequately to likely developments, such as a recession, worsening waiting lists, further liberalisation (i.e. the application of market forces in health care) and, by way of extension, the ongoing integration of 'Europe' is questioned.

Health Care Rationing↗

Are recessions good for workplace safety?

Empirical evidence shows that in recessions the rate of workplace accidents goes down. This paper presents a theory and an empirical investigation to explain this phenomenon. The theory is based on the idea that reporting an accident affects the reputation of a worker and raises the probability that he is fired. If the unemployment rate is high, a worker faces a big loss when fired and fewer workplace accidents are reported. The empirical investigation concerns workplace accidents in 16 OECD countries. We conclude that cyclical fluctuations in workplace accident rates have to do with reporting behavior of workers and not with changes in workplace safety.

Absenteeism↗

[Occurrence and economic importance of congenital hernia in German Fleckvich calves].

The frequency of congenital hernia was investigated in German Fleckvieh calves being driven up for sale on livestock markets for breeding and fattening calves in Miesbach and Traunstein. Data were collected on 77 livestock auctions in the years 1996 and 1997. Altogether 53,105 calves were examined and 1.8% of these calves showed a congenital umbilical hernia. The incidence of umbilical hernia was significantly influenced by the sex of the calf, the occurrence of multiple births, the market place/market date, the sire and the sire line. Red Holstein blood proportion, lactation number, duration of pregnancy and 305 day milk performance were not of significant importance. Herd milk level did not influence the incidence of congenital umbilical hernia, however, herdmate averages for calves differed significantly in their incidence. The average difference of the market price between male calves affected by congenital umbilical hernia and not affected male calves amounted to 75 DM, in female calves, however, only to 38 DM. The risk, that a congenital umbilical hernia is not closing within an age of 15 months, depends on the width of the hernial opening in the newborn calf. An opening of 4 cm and more has only a healing chance of 50% and less. However, negative effects on fattening and carcass traits could be not found. The genetic influence on congenital umbilical hernia was obvious. The analyses indicated that the incidence of congenital umbilical hernia observed could not be explained by one autosomal recessive gene locus, but it seemed much more likely that more than one gene locus is involved or a mixed multifactorial monogenic mode of inheritance may be the underlying genetic mechanism. Breeders should be aware of the implications of congenital hernias and thus, congenital hernia should get more attention in the selection process of young sires.

Animals↗

Evaluation of a mass screening program for lysinuric protein intolerance in the northern part of Japan.

Lysinuric protein intolerance (LPI:MIM 222700) is an autosomal recessive disease characterized by defective transport of the dibasic amino acids. We recently reported a local cluster of LPI in the northern part of Japan (Koizumi et al., 2000). Mutational analysis of the LPI patients in this local cluster revealed they were exclusively homozygous for the R410X mutation. The effectiveness of early intervention with citrulline therapy (200 mg/kg per day) and protein restriction (1.5 g/kg per day) was confirmed in these patients. Mass screening was conducted in 4,568 newborn babies between 1999 and 2002, which was estimated to cover 100% of almost all newborns delivered in the screened area. Forty heterozygous newborns were found (0.88%), leading to an estimated incidence of LPI of 1:51,984. The number of people that required screening to detect one case was 51,984, and the cost for mass screening was 30 cents/person (a total of dollars 15,600). This is comparable to, or even less than, the cost of currently screened diseases in Japan. Therefore, we conclude that a mass screening program for LPI can be introduced effectively and economically into an area where an LPI cluster is located as the result of a founder mutation.

Adolescent↗

Effects of global competition on health care administration in Finland and the United States. What you can do to save your practice.

Global competition, a faltering Finnish economy, and deep recession are forcing difficult decisions on the health care administrators of this Nordic country known for its extensive social welfare safety net and socialized health care system. In the first part of this article the Finnish health care system and its problems, as well as possible solutions, are presented. Similarities to our own system are noted and discussed. In an interview, the director general for the Minister of Social Affairs and Health of Finland, Kimmo Leppo, expressed concern about future funding sources in his country for the same levels of social welfare and health care programs that presently exist. The Finns are considering managed competition among providers, increasing copayments, excess hospital beds, anticipated hospital closures in their country, block grants, and how to deal with rising physician unemployment. He was interested in the proposed US government health care plans, and especially the state of Tennessee's TennCare plan, a state plan that closely resembled the failed Clinton health care reform package. The second part of this article explores how global competition has brought the pressure of modern competitive economics into the US medical arena.

Cost Savings↗

Genetics and bone. Using the mouse to understand man.

The rationale for use of inbred strains of mice in bone research is well recognized and includes: a) practical factors (economics of scale, rapid development of adult status, pre-existing knowledge, down-sized technologies) and b) proven methodologies for genetic studies (polygenic trait analyses, mapping tools, genomic sequencing, methods for gene manipulation). Initial investigations of inbred strains of mice showed that femoral and lumbar vertebral volumetric bone mineral density (BMD, mg/mm(3)) by pQCT varied in excess of 50% for femurs and 9% in vertebral BMD. Two strains - low BMD C57BL/6J (B6) mice and high BMD C3H/HeJ (C3H) - were investigated for insights to their BMD diversity. B6C3F2 females derived from intercrossing B6C3F1s were raised to adult skeletal status at 4 months, then necropsied for phenotyping of bone and genotyping of genomic DNA. 1000 F2 females were genotyped for PCR product polymorphisms on all 19 autosomes at approximately 15 cM. Genome wide analyses for genotype-phenotype correlations showed 10 chromosomes (Chrs) carried genes for femoral and 7 Chrs for vertebral BMD. LOD scores ranged from 2.90 to 24.4, and percent of F2 variance accounted for ranged from 1 to 10%. Analyses of main effects revealed both dominant-recessive and additive inheritance patterns. Both progenitor strains carried alleles with positive and negative effects on BMD of each bone sites. A remarkable array of additonal skeletal phenotypes (femur and vertebral geometry, strength measures, serum markers) also proved polygenic in nature, with complex segregation patterns. Verification of BMD quantitative trait loci (QTLs) was undertaken by creating congenic B6 strains carrying individual QTL regions from C3H. Following 6 cycles of backcrossing a QTL-containing region from C3H to the B6 strain, N6F2 congenic strain mice were aged to 4 months, then genotyped for the QTL region and phenotyped for skeletal traits. Comparison of mice homozygous for C3H alleles versus homozygous for B6 alleles in the QTL regions showed that femoral BMD increased or decreased significantly in congenic strains, as was predicted from F2 data. Gender differences specific to BMD QTLs have been revealed, as have more than 30 additional phenotypes associated with cortical and trabecular structural parameters and biomechanical properties.

Journal Article↗

Tobamoviruses: Advances in Molecular Biology, Host Interactions and Integrated Disease Management.

Tobamoviruses (viruses in the genus Tobamovirus, family Virgaviridae) lead to major yield losses in economically important crops around the world. In this review, we go beyond the canonical gene expression framework by integrating recent discoveries of reverse open reading frames (rORFs) on the negative-strand RNA. These rORFs have only been experimentally validated in cucumber green mottle mosaic virus (CGMMV), with predicted sequence-conserved homologs across a subset of the genus, including TMV, ToBRFV, and PMMoV. However, they are not universally present in all tobamoviruses. We systematically dissect the infection cycle-from disassembly and replication to cell-to-cell and systemic movement-with an emphasis on the host factors hijacked at each stage. We synthesize current understanding of plant antiviral immunity, focusing on RNA silencing and NLR receptor-mediated resistance as two pillars of defense, along with the transcription factors and microRNAs that orchestrate these responses. We critically evaluate the experimental evidence for both plant defenses and viral counter-strategies, noting that many mechanistic models derive from limited model systems. We further characterize host genetic resistance and susceptibility factors applicable to crop breeding. These resources include dominant NLR and non-NLR resistance, as well as recessive resistance derived from modified host susceptibility genes. We address how viral mutations, recombination and fitness trade-offs undermine resistance durability. We then evaluate their practical deployment through conventional breeding, the exploitation of quantitative resistance, and genome editing, and outline associated agronomic drawbacks and regulatory constraints. Using ToBRFV as a case study, we analyze its epidemiological traits and assess the current arsenal of surveillance tools, from field diagnostics to remote sensing. Finally, we survey management strategies across a spectrum of maturity. Some approaches, including sanitation protocols and conventionally bred resistant cultivars, have proven effective under field conditions. The first dsRNA-based biopesticide has recently been registered in China, while other biological control agents and low-risk chemical approaches remain largely at the experimental stage. We also discuss the bottlenecks that impede lab-to-field transition and highlight promising solutions such as precision breeding and evolution-oriented cultivar deployment. By bridging molecular virology, epidemiology, and integrated disease management, this review provides a critical, bench-to-field framework for the sustainable control of tobamoviruses.

TMV↗

Successful allogeneic peripheral blood stem cell transplantation in Wiskott-Aldrich Syndrome Patients: first report in Thailand.

Wiskott-Aldrich syndrome (WAS), an X-linked recessive disorder, is characterized by primary progressive T cell immunodeficiency, impaired antipolysaccharide antibody production, eczema, and thrombocytopenia. Stem cell transplantation is the only curative therapy. To evaluate the use of allogeneic peripheral stem cell transplantation (PBSCT) in this group of patients, we performed allogeneic PBSCT in two WAS patients (3 and 12 years old). The conditioning regimen consisted of busulfan 4 mg/kg/day for 4 days, and cyclophosphamide 50 mg/kg/day for 4 days. Graft-versus-host disease prophylaxis was consistent with cyclosporin A and methotrexate. Peripheral blood stem cells were collected from their brother donors (6 and 16 years old) by continuous flow leukapheresis after mobilization with granulocyte-colony-stimulating factor at a dose of 7.5 microg/kg/day for 5 days. Both recipients achieved neutrophils engraftment on days 11 and 12. The first patient achieved platelets engraftment on day 30. The second patient did not have platelet count below 20.0 x 10(9)/l during PBSCT procedure. Both did not develop acute or chronic graft-versus-host disease. At present, they are healthy after PBSCT. The follow up time after transplantation is 1,170 days and 269 days, respectively. Allogeneic PBSCT is economically feasible for WAS. The cost of PBSCT in Thailand is 20 to 30% less than bone marrow and cord blood stem cell transplantation. The cost of the transplant procedure for each patient in Thailand is US $ 12,000. This study is the first report of a successful stem cell transplantation in WAS patients in Thailand.

Adolescent↗

Strategic aspects of the purchasing process in the Finnish hearing instruments business.

Discusses the Finnish hearing instrument market which, in the past decade, has been characterized by both closed and shared markets. Indicates there has been some formal competition, but real price competition has not influenced the resharing of market shares. Finds that the current recession has forced hospitals to re-evaluate their purchasing criteria. Investigates the process with the help of industrial marketing theories to determine the strategic means which can be used to create competitive advantages. The new automatic data-processing (ADP)-based high technology in the hearing-instrument business provides opportunities for identifying these advantages. Surveys the abilities of hearing-centre personnel in university hospitals to take advantage of ADP-based tools. Shows that hearing-centre personnel have a low level of ADP knowledge and, thus, a great need for ADP training. Discusses the ADP-based strategy chosen to be AP Medical Hearing Ltd's main strategy and emphasizes the importance of ADP-based training in high technology.

Decision Making, Organizational↗

Micro-level analysis of distributional changes in health care financing in Finland.

OBJECTIVES: In the early 1990s the Finnish economy suffered a severe recession at the same time as health care reforms were taking place. This study examines the effects of these changes on the distribution of contributions to health care financing in relation to household income. Explanations for changes in various indicators of health care expenditure and use during that time are offered. METHOD: The analysis is based partly on actual income data and partly on simulated data from the base year (1990). It employs methods that allow the estimation of confidence intervals for inequality indices (the Gini coefficient and Kakwani's progressivity index). RESULTS: In spite of the substantial decrease in real incomes during the recession, the distribution of income remained almost unaltered. The share of total health care funding derived from poorer households increased somewhat, due purely to structural changes. The financial plight of the public sector led to the share of total funding from progressive income taxes to decrease, while regressive indirect taxes and direct payments by households contributed more. CONCLUSIONS: It seems that, aside from an increased financing burden on poorer households, Finland's health care system has withstood the tremendous changes of the early 1990s fairly well. This is largely attributable to the features of the tax-financed health care system, which apportions the effects of financial and functional disturbances equitably.

Cost Sharing↗

Primary hyperoxaluria in infants: medical, ethical, and economic issues.

OBJECTIVES: Survey on the current medical approach to and the economic issues affecting infants with primary hyperoxaluria type 1. METHODS: Questionnaire to specialized centers worldwide. RESULTS: Seventy-eight infants were identified: 44% were of Muslim origin and 56% were not. The consanguinity rate was 76% and 0%, respectively. Thirty-three percent were treated in developing countries (group 1) and 67% in developed countries (group 2). Initial presentation (4.9 +/- 2.8 months) consisted of failure to thrive (22%), urinary tract infection (21%), and uremia (14%). Radiologic findings included nephrocalcinosis (91%), urolithiasis (44%), or both (22%). The diagnosis was based on family history, tissue biopsy, and urine oxalate level in most patients from group 1 and on urine oxalate and glycolate levels, alanine:glyoxalate aminotransferase activity, and DNA analysis in patients from group 2. Therapeutic withdrawal was the final option for 40% of children; financial reasons were given for 10 of 17 patients from group 1 and 0 of 9 from group 2. End-stage renal disease started at 3.2 +/- 6.4 years of age and was present in half of the patients at the time of diagnosis. Fifty-two percent of the patients died: 82% in group 1 versus 33% in group 2; 33% of patients who underwent transplantation died versus 71% of those who did not. CONCLUSION: The management of primary hyperoxaluria type 1 in infants is a major example of the ethical, epidemiologic, technical, and financial challenges that are raised by recessive inherited diseases with early life-threatening onset. In certain circumstances, oxalosis can be regarded as a condition for which therapeutic withdrawal may be an acceptable option.

Developed Countries↗

[Mentoring program].

Due to drastic changes in the business environment and prolonged recession, stress management practices in business organizations have been encountering two kinds of problems: budget cuts and difficulties in the delivery of services. The feasibility of mentoring programs to cope with these two problems is discussed. Through an extensive review of the literature, it becomes clear that mentoring programs have the following features and advantages; (1) One to one relationship between elder mentor and younger protégé has a favorable effect on the both mentor and protégé's mental health. (2) Formal mentoring programs are widely used in the U.S. for the prevention of juvenile delinquency, professional education, and human resource development in business settings. (3) Mentoring programs, in general, are practiced with the cooperation of kindred volunteers and professionals who monitor the mentor-protégé relationships. (4) Since a mentoring program utilizes a wide range of human resources in work organizations, it is able to overcome the "budget and delivery" problems. Further discussions are about the comparison with listener programs as well as the relationship with the total human resource management system.

Adaptation, Psychological↗

The BOTRYTIS SUSCEPTIBLE1 gene encodes an R2R3MYB transcription factor protein that is required for biotic and abiotic stress responses in Arabidopsis.

The molecular and cellular mechanisms involved in plant resistance to the necrotrophic fungal pathogen Botrytis cinerea and their genetic control are poorly understood. Botrytis causes severe disease in a wide range of plant species, both in the field and in postharvest situations, resulting in significant economic losses. We have isolated the BOS1 (BOTRYTIS-SUSCEPTIBLE1) gene of Arabidopsis based on a T-DNA insertion allele that resulted in increased susceptibility to Botrytis infection. The BOS1 gene is required to restrict the spread of another necrotrophic pathogen, Alternaria brassicicola, suggesting a common host response strategy against these pathogens. In the case of the biotrophic pathogens Pseudomonas syringae pv tomato and the oomycete parasite Peronospora parasitica, bos1 exhibits enhanced disease symptoms, but pathogen growth is similar in bos1 and wild-type plants. Strikingly, bos1 plants have impaired tolerance to water deficit, increased salinity, and oxidative stress. Botrytis infection induces the expression of the BOS1 gene. This increased expression is severely impaired in the coi1 mutant, suggesting an interaction of BOS1 with the jasmonate signaling pathway. BOS1 encodes an R2R3MYB transcription factor protein, and our results suggest that it mediates responses to signals, possibly mediated by reactive oxygen intermediates from both biotic and abiotic stress agents.

Amino Acid Sequence↗