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Association studies between microsatellite markers within the gene encoding human 11beta-hydroxysteroid dehydrogenase type 1 and body mass index, waist to hip ratio, and glucocorticoid metabolism.

Two isozymes of 11beta-hydroxysteroid dehydrogenase (11beta-HSD) interconvert active cortisol (F) and inactive cortisone (E). 11beta-HSD1 is an oxo-reductase (E to F) expressed in several glucocorticoid target tissues, including liver and adipose tissue, where it facilitates glucocorticoid-induced gluconeogenesis and adipocyte differentiation, respectively. We have isolated a full-length HSD11B1 genomic clone; the gene is more than 30 kb in length, not 9 kb in length as previously reported, principally due to a large intron 4. Two polymorphic (CA)(n) repeats have been characterized within intron 4: a CA(19) repeat 2.7 kb 3' of exon 4 and a CA(15) repeat 3 kb 5' of exon 5. The microsatellites, CA(19) and CA(15), were PCR amplified using fluorescent primers and were genotyped on an ABI 377 DNA sequencer from DNA of 413 normal individuals enrolled in the MONICA study of cardiovascular risk factors and 557 Danish men (ADIGEN study), of whom 234 were obese [body mass index (BMI), >/=31 kg/m(2) ] at draft board examination and 323 were randomly selected controls from the draftee population with BMI below 31 kg/m(2) (mean +/- SE, 21.7 +/- 0.41). Genotypic data from the normal MONICA cohort was compared with gender, 5beta-tetrahydrocortisol+5alpha-tetrahydrocortisol/tetrahydrocortisone ratio, and waist to hip (W:H) ratio. When analyzed by allele length (0, 1, or 2 short alleles) for the CA(19) marker, there was a trend toward a higher 5beta-tetrahydrocortisol+5alpha-tetrahydrocortisol/tetrahydrocortisone ratio (P = 0.058) and an increased W:H ratio (2 vs. 0.1 short; P(c) = 0.10) with overrepresentation of short alleles. The opposite was true for the CA(15) locus, with longer alleles at this locus predicting increased 11beta-HSD1 activity, particularly in females. Genotypic data from the ADIGEN case-control population was compared with clinical markers of obesity such as BMI and W:H ratio. There was no significant difference in the distribution of either microsatellite marker between lean and obese groups. Allele distributions were binomial, as seen for the MONICA cohort, and the data were split accordingly (zero, one, or two short alleles). No significant association was seen between grouped alleles and the clinical parameters. No association was observed between HSD11B1 genotype and BMI in either population. These data suggest that 11beta-HSD1 is not a major factor in explaining genetic susceptibility to obesity per se. However, weak associations between HSD11B1 genotype, increased 11beta-HSD1 activity, and W:H ratio suggest that polymorphic variability at the HSD11B1 locus may influence susceptibility to central obesity through enhanced 11beta-HSD1 activity (E to F conversion) in visceral adipose tissue.

11-beta-Hydroxysteroid Dehydrogenase Type 2↗

Statistical models for genetic susceptibility in toxicological and epidemiological investigations.

Models are presented for use in assessing genetic susceptibility to cancer (or other diseases) with animal or human data. Observations are assumed to be in the form of proportions, hence a binomial sampling distribution is considered. Generalized linear models are employed to model the response as a function of the genetic component; these include logistic and complementary log forms. Susceptibility is measured via odds ratios of response, relative to a background genetic group. Significance tests and confidence intervals for these odds ratios are based on maximum likelihood estimates of the regression parameters. Additional consideration is given to the problem of gene-environment interactions and to testing whether certain genetic identifiers/categories may be collapsed into a smaller set of categories. The collapsibility hypothesis provides an example of a mechanistic context wherein nonhierarchical models for the linear predictor can sometimes make sense.

Animals↗

Physician substance abuse impairment: anesthesiologists vs. other specialties.

This is a retrospective case control study comparing relapse and recovery rates between addicted anesthesiologists and other physicians. Thirty-two anesthesiologists were compared with thirty-six randomized physician controls; all were followed for an average of 7.5 years over a 12-year period by the Medical Society of New Jersey's Physician Health Program. The relapse rate among anesthesiologists was 13 (40%) and for controls were 16 (44%). Sustained recovery rates longer than two years were 26 (81%) and 31 (86%), respectively. Binomial and Kolmogorov-Sminov analysis showed no statistical significance between these two groups (p = 0.749 and p = 0.589). These groups were stratified for residents vs. attendings and for those who changed their primary specialty during treatment and again, no statistical significance was noted between the two groups. The only significant difference in the groups noted was a higher opiate abuse rate for anesthesiologists (78%) vs. other physicians (42%) (p = 0.002). These findings suggest that with aggressive follow up and monitoring, clinicians can expect similar relapse and recovery rates for anesthesiologists as others.

Anesthesiology↗

Stillbirth pattern in an isolated mediterranean population: La Alpujarra, Spain.

This study attempted to analyze the effect of several factors on the stillbirth pattern in a relatively isolated rural population, La Alpujarra (Spain), during the first half of the 20th century. The study was a retrospective analysis from a total sample of 2199 births to 525 mothers, allowing for birth year of mother, maternal age, parental inbreeding, family size, birth order, sex, single/twin delivery, and birth interval. Binomial probability distribution of stillbirths provided no evidence for any significantly increased risk in relation to family size. Analysis of covariance (ANCOVA) of stillbirth risk in affected families indicated a significant effect for sex of the child, parental consanguinity, and birth year of mother. Logistic regression showed increased risk in twin delivery and pregnancy order one, but not for birth order other than one. Multivariate analysis of variance (MANOVA) testing for differences between affected and unaffected families supported a temporal decrease of stillbirths during the period studied. Although the birth interval average was significantly shorter in affected families (p < 0.0001), this association did not hold, in a more detailed analysis, for individual intervals in these families (p = 0.20). There was no significant effect of maternal age on stillbirths in the whole sample or limited to first pregnancies. These results suggest that birth order one and twin delivery were the main determinants of the stillbirth pattern in La Alpujarra. Furthermore, our data indicate that the decline in stillbirth rate began before medical facilities for perinatal care became available, which was not until after 1950. The temporal decrease in stillbirth rates may therefore be related to an increasing social attention to deliveries rather than to prenatal care medical facilities.

Adult↗

Comparison of populations as a function of confidence intervals of gene probability.

A new method for population comparison has been developed in order to determine the most discriminating systems in relation to diverse populations. The method compares pairs of populations on the basis of confidence intervals for allelic frequencies and does not require any previous assumption, such as normality of the population. A data set of 12 populations studied for Polymarker Kit (Roche) genetic systems, 13 biallelic systems (LDLR, GYPA, D7S8) and two systems with three alleles each (HBGG, GC), was considered. The analysis produced a total of 144 confidence intervals (12 populations x 12 alleles). The raw data were then analyzed comparing pairs of populations, allele by allele, through their respective confidence intervals. The method calculates the matrix of similarity between pairs of populations for each allele and eventually for each genetic system. Finally, the 12 populations were classified depending on the number of nondiscriminating alleles. The results of this method are compared to those produced by such usual techniques as Principal Component Analysis.

Alleles↗

Use of monozygotic twins in search for breast cancer susceptibility loci.

We have used Swedish monozygotic twins concordant for breast cancer to study genetic changes associated with the development of breast cancer. Because loss of heterozygosity (LOH) at a specific genomic region may reflect the presence of a tumour suppressor gene, loss of the same allele in both of the twins concordant for breast cancer may pinpoint a tumour suppressor gene that confers a strong predisposition to breast cancer. DNA samples extracted from the matched tumour and normal tissues of nine twin pairs were analysed for allelic imbalance using a set of microsatellite markers on chromosomes 1, 13, 16 and 17, containing loci with known tumour suppressor genes. The two main regions, where more twin pairs than expected had lost the same allele, were located at 16qtel', including markers D16S393, D16S305 and D16S413, and at 17p13, distal to the p53 locus. Our results show that the monozygotic twin model can be used to suggest candidate regions of potential tumour suppressor genes, even with a limited number of twin pairs.

Adult↗

Inferences from a community study about non-epileptic events.

OBJECTIVE: To demonstrate the epidemiological importance of the different types of non-epileptic events (NEE) in a low-income urban community. METHOD: The patients suspected of having epilepsy, who were detected in the first phase (screening one) of this prevalence study, were interviewed by a neurologist in a non-structured neurological interview. These NEE were classified as physiological and psychogenic, subdivided by various types. The psychogenic NEE were classified according to the DSM-IV criteria. RESULTS: We compared the cases suspected of having epilepsy (n=176) with those not suspected (n=806) and discovered that those cases suspected of having epilepsy had a greater median age (<0.01) and female predominance (p<0.01). Among the cases suspected of having epilepsy there were different diagnosis: epileptic events without identifiable cause (n=20) or with identifiable causes (e.g., febrile convulsions and eclampsia). The most prevalent diagnosis for those suspected of having epilepsy was syncope (n=63; 35.8%). In terms of physiological events, the most frequent were: epileptic seizures, paroxysmal toxic phenomena (including alcoholism) and brain trauma, besides syncope; in terms of psychogenic events the most frequent were: dissociative and anxiety disorders. Regarding gender differences, paroxysmal toxic problems were significantly more prevalent in men (p= 0.02), and dissociative disorders (p=0.01) in women. CONCLUSION: This survey confirms the epidemiological importance of syncope in a populational sample with NEE. However, among the psychogenic disorders of this NEE sample, the most frequent were dissociative and anxiety phenomena. This finding contrasts with the literature based on samples from tertiary epileptic centers with video-EEG resources, which found somatoform disorders to be more prevalent than dissociative and anxiety phenomena.

Adolescent↗

[Use of an artificial neural network for detecting excess deaths due to cholera in Ceará, Brazil].

OBJECTIVE: To evaluate recurrent neural networks as a predictive technique for time-series in the health field. METHODS: The study was carried out during a cholera epidemic which took place in 1993 and 1994 in the state of Ceará, northeastern Brazil, and was based on excess deaths having 'poorly defined intestinal infections' as the underlying cause (ICD-9). The monthly number of deaths with due to this cause between 1979 and 1995 in the state of Ceará was obtained from the Ministry of Health's Mortality Information System (SIM). A network comprising two neurons in the input layer, twelve in the hidden layer, one in the output layer, and one in the memory layer was trained by backpropagation using the fist 150 observations, with 0.01 learning rate and 0.9 momentum. Training was ended after 22,000 epochs. We compare the results with those of a negative binomial regression. RESULTS: ANN forecasting was adequate. Excessive mortality (number of deaths above the upper limit of the confidence interval) was detected in December 1993 and October/November 1994. However, negative binomial regression detected excess mortality from March 1992 onwards. CONCLUSIONS: The artificial neural network showed good predictive ability, especially in the initial period, and was able to detect alterations concomitant and a subsequent to the cholera epidemic. However, it was less precise that the binomial regression model, which was more sensitive to abnormal data concomitant with cholera circulation.

Binomial Distribution↗

Clinical and mycological study of scalp white piedra in the State of Paraíba, Brazil.

White piedra is a superficial mycoses characterized by nodules on the hair shaft, caused by the basidiomycetous yeasts. In the present study, clinical and mycological findings of scalp white piedra caused by Trichosporon spp. are related. Twenty three cases of scalp white piedra were observed with a high incidence in women (87%) and preschool children from 2 to 6 (74%) years old. These groups presented a relationship of dependence with this infection. Despite the low socio-economic status, poor standards of hygiene, (48% of the patients) as well as the fact that 30.4% of the children shared the same nursery, these factors were not significant for the transmission of the mycosis. These were the first reports of scalp white piedra in João Pessoa city, Paraíba, Brazil.

Adolescent↗

[Chlamydia infection impact among native Indian groups of the Brazilian Amazon region].

Knowledge is limited on the spread of bacteria from genus Chlamydia in Brazil. This study included a sero-epidemiological survey of 2,086 samples from native Indian populations of the Brazilian Amazon region. Sera were screened using indirect immunofluorescence assay for detection of antibodies to C. trachomatis serotype L2, followed by microimmunofluorescence assay using fifteen C. trachomatis and C. pneumoniae serotypes as antigen substrates. Antibody prevalence was 48.6%, but there was a large prevalence range among the groups, including those that had never been challenged with the bacteria, as well as those in which almost all individuals had been infected. Titration of IgG antibodies and detection of specific IgM in high-titer samples showed the persistence of Chlamydia in 6.1% of the reactive individuals, who probably play an important role as reservoirs for dissemination of the bacteria. Specific seroreactivity to C. trachomatis showed the presence of serotypes A, B, Ba, D, E, G, H, I, and L1 in the geographic area surveyed. Furthermore, the survey showed that C. pneumoniae was also infecting these individuals. Both species may be involved in a significant human disease burden that merits further clarification.

Binomial Distribution↗

[Hysterosonography: evaluation of the uterine cavity in women with abnormal uterine bleeding].

OBJECTIVE: To compare the diagnostic accuracy of sonohysterography with that of hysteroscopy and ultrasonography for the diagnosis of uterine alterations with abnormal uterine bleeding. METHODS: Fifty three patients scheduled for hysteroscopy at the Hysteroscopy Sector of the Women's Hospital (CAISM) at the "Universidade Estadual de Campinas" (Brazil) were included in the study. Sensitivity and specificity of the three propaedeutic methods were compared using histology as the gold standard. RESULTS: Sensitivity of sonohysterography and of hysteroscopy was 94% and that of ultrasonography 83%. The specificity of sonohysterography was 77%, of hysteroscopy 91% and of ultrasonography 69%. There were no significant differences between sensitivities of the three methods. However, a significant difference was found between the specificity of ultrasonography and hysteroscopy. Sonohysterography demonstrated a much greater capability than ultrasonography to identify endometrial polyps. CONCLUSION: Sonohysterography may be used to complement ultrasonography and to substitute hysteroscopy, for the diagnosis of alterations that result in abnormal uterine bleeding.

Adult↗

Accounting for cluster sampling in constructing enumerative sequential sampling plans.

Green's sequential sampling plan is widely used in applied entomology. Green's equation can be used to construct sampling stop charts, and a crop can then be surveyed using a simple random sampling (SRS) approach. In practice, however, crops are rarely surveyed according to SRS. Rather, some type of hierarchical design is usually used, such as cluster sampling, where sampling units form distinct groups. This article explains how to make adjustments to sampling plans that intend to use cluster sampling, a commonly used hierarchical design, rather than SRS. The methodologies are illustrated using diamondback moth, Plutella xylostella (L.), a pest of Brassica crops, as an example.

Animals↗

Sampling for the sugarcane borer (Lepidoptera: Crambidae) on sugarcane in Louisiana.

A 3-yr study was conducted in 0.6- to 2.0-ha sugarcane fields throughout south Louisiana under varying sugarcane borer, Diatraea saccharalis (F.), density levels to determine the spatial dispersion of infestations and to develop a sequential sampling plan. Infestations of D. saccharalis were randomly dispersed. Infestation levels (percentage of stalks infested) ranged from 0.6 to 33.3%. Frequency distributions of the number of infested stalks indicated that the Poisson distribution best fit the data Tests of other distributions (negative binomial [aggregated], binomial [uniform], geometric, and hypergeometric) resulted in poorer fits. The sequential sampling plan devised, with lower and upper D. saccharalis infestation limits of 2 and 5% and 5 and 10%, required maximum average sample numbers of 7.1 and 5.5 (20-stalk samples), respectively, to make terminating management decisions. It is our assessment that implementation of these plans would decrease sampling effort by 50-60% when compared with sampling programs currently in use for D. saccharalis management decisions in Louisiana.

Animals↗

Parasite body size and interspecific variation in levels of aggregation among nematodes.

The aggregation of parasites among individual hosts is one of the best documented features of parasite populations; we still do not know, however, why certain parasite species are more highly aggregated than other, related species. Here we search for a general explanation of interspecific variation in aggregation levels, based on the relationship between parasite body size and fecundity, transmission success, and intensity-dependent population regulation. We test the prediction that larger-bodied parasite species are more weakly aggregated than smaller-bodied related species, in a comparative analysis across parasitic nematode species. Across species, the variance-to-mean abundance ratio correlated negatively and significantly with nematode body sizes, as predicted. All other tests, however, including the more robust analyses controlling for phylogenetic influences, failed to support this result. This is mainly because the variance in infection levels is almost completely explained by mean parasite abundance. For this reason, it may prove difficult to identify a general biological explanation for interspecific variability in aggregation levels among parasites.

Animals↗

Can helminth community patterns be amplified when transferred by predation from intermediate to definitive hosts?

Helminth communities in definitive hosts are formed by the acquisition of packets of larvae arriving each time an intermediate host is consumed. It is thus possible that associations between parasite species or other aspects of community structure get transferred from intermediate to definitive hosts. Earlier computer simulations showed that associations between 2 parasite species, in particular positive associations, could be transferred up the food chain. Here, we alter some of the assumptions of previous models and generate new simulations of several ways in which source infracommunities in intermediate hosts can be transferred to target infracommunities in definitive hosts. In particular, we introduced nonrandom selection of intermediate hosts by predatory definitive hosts, to mimic the phenomenon of host manipulation by parasites; this consisted in biasing predation toward intermediate hosts harboring a certain parasite species. Overall, our results show that positive covariances between 2 parasite species can not only be transferred but can also be amplified during transmission to definitive hosts; significant covariance between parasite species can even appear in the definitive hosts when none existed in the intermediate hosts. Negative covariance was not as readily transferred to definitive hosts and amplified, in part because of properties of the presence-absence covariance index. Amplification of covariance results from intermediate host manipulation as well as from other processes taking place during transmission. These results suggest that the patterns of association between helminth species in definitive hosts cannot be taken to reflect the processes acting inside those hosts: they may simply be inherited, with amplification, from intermediate hosts.

Animals↗

Comparing parasite numbers between samples of hosts.

The comparison of parasite numbers or intensities between different samples of hosts is a common and important question in most parasitological studies. The main question is whether the values in one sample tend to be higher (or lower) than the values of the other sample. We argue that it is more appropriate to test a null hypothesis about the probability that an individual host from one sample has a higher value than individual hosts from a second sample rather than testing hypotheses about means or medians. We present a recently proposed statistical test especially designed to test hypotheses about that probability. This novel test is more appropriate than other statistical tests, such as Student's t-test, the Mann-Whitney U-test, or a bootstrap test based on Welch's t-statistic, regularly used by parasitologists.

Animals↗