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Algorithmic reproduction of asymmetry and border cut-off parameters according to the ABCD rule for dermoscopy.

BACKGROUND: Semiquantitative algorithms were applied to dermoscopic images to improve the clinical diagnosis for melanoma. OBJECTIVE: The aim of the study was to develop a computerized method for automated quantification of the 'A' (asymmetry) and 'B' (border cut-off) parameters, according to the ABCD rule for dermoscopy, thus reproducing human evaluation. METHODS: Three hundred and thirty-one melanocytic lesion images, referring to 113 melanomas and 218 melanocytic nevi, acquired by means of a digital videodermatoscope, were considered. Images were evaluated by two experienced observers and by using computer algorithms developed by us. Clinical evaluation of asymmetry was performed by attributing scores to shape asymmetry and asymmetry of pigment distribution and structures, whereas computer evaluation of shape and pigment distribution asymmetries were based on the assessment of differences in area and lightness in the two halves of the image, respectively. Borders were evaluated both by clinicians and by the computer, by attributing a score to each border segment ending abruptly. Differences between nevus and melanoma values were evaluated using the chi-square test, while Cohen's Kappa index for agreement was employed for the evaluation of the concordance between human and computer. RESULTS: Pigment distribution asymmetry appears the most striking parameter for melanoma diagnosis both for human and for automated diagnosis. A good concordance between clinicians and computer evaluation was achieved for all asymmetry parameters, and was excellent for border cut-off evaluation. CONCLUSIONS: These algorithms enable a good reproduction of the 'A' and 'B' parameters of the ABCD rule for dermoscopy, and appear useful for diagnostic and learning purposes.

Algorithms↗

Effects of vitamin C deficiency on physiology of male reproductive organs of guinea pigs.

Vitamin C dietary deficiency in guinea pigs markedly affected the androgen-sensitive parameters of the reproductive tissues--testis, epididymis, vas deferens, and accessory sex glands--and caused an "androgen-deprived effect" in these target organs. This in turn altered their internal milieu and caused changes in their metal ion profile and the morphology, motility, and density of spermatozoa in the cauda epididymis and vas deferens. The sensitivity of the vas deferens to adrenaline was also reduced in scorbutic guinea pigs, thus decreasing their fertility rate. The primary action seems to be at the level of the testis, and androgen deprivation and partial antifertility effects are probably secondary manifestations consequent to the primary effect. The present study demonstrated that ascorbic acid is essential for maintaining the physiological integrity of the androgen target reproductive organs in guinea pigs.

Animals↗

[Electrostimulation-induced stapedius reflex. Presentation of a standardized procedure and results of clinical studies].

The electro-tactile elicitation of the stapedius muscle reflex is well known but not used in clinical practice. Despite a complex reflex pathway in the brainstem, correlations between reflex parameters and neurological impairments are still possible. We have developed a method for eliciting the electro-tactile stapedius muscle reflex and automatic analysis of different reflex parameters by using an analog-digital converter and a personal computer-integrated signal analysis system. Clinical investigations were carried out with a group of 55 healthy persons (control group), 13 patients with central facial palsies, 51 patients with multiple sclerosis (MS group) and 24 patients with absent acoustic-stapedius muscle reflexes. Findings demonstrated that the latency between stimulus and beginning of the reflex (L1) was significantly longer in the MS group compared with the control group. The best parameter for dividing the MS group into groups with different disability scores was S, which was the parameter for the increase in the L1 growth curve at different stimulus levels. Reproduction of the parameter S in repeated tests with different locations of the stimulus-electrode was excellent.

Brain Damage, Chronic↗

Oral (drinking water) two-generation reproductive toxicity study of bromodichloromethane (BDCM) in rats.

Bromodichloromethane (BDCM) was tested for reproductive toxicity in a two-generation study in CRL SD rats. Thirty rats/sex/ group/generation were continuously provided BDCM in drinking water at 0 (control carrier, reverse osmosis membrane-processed water), 50,150, and 450 ppm (0, 4.1 to 12.6, 11.6 to 40.2, and 29.5 to 109.0 mg/kg/day, respectively). Adult human intake approximates 0.8 microg/kg/day (0.0008 mg/kg/day). P and F1 rats were observed for general toxicity (viability, clinical signs, water and feed consumption, body weights, organ weights [also three weanling Fl and F2 pups/sex/litter], histopathology [10/sex, 0- and 450-ppm exposure groups]) and reproduction (mating, fertility, abortions, premature deliveries, durations of gestation, litter sizes, sex ratios, viabilities, maternal behaviors, reproductive organ weights [also three weanling Fl and F2 pups/sex/ litter], sperm parameters, and implantations. F1 rats were evaluated for age at vaginal patency or preputial separation. Ten P and F1 rats/sex from the 0- and 450-ppm exposure groups and rats at 50 and 150 ppm with reduced fertility were evaluated for histopathology (gross lesions, testes, intact epididymis, all F1 dams for number of primordial follicles). Developmental parameters in offspring included implantation and pup numbers, sexes, viabilities, body weights, gross external alterations, and reproductive parameters (Fl adults). Toxicologically important, statistically significant effects at 150 and/or 450 ppm included mortality and clinical signs associated with reduced absolute and relative water consumption, reduced body weights and weight gains, and reduced absolute and relative feed consumption (P and F1 rats). Significantly reduced body weights at 150 and 450 ppm were associated with reduced organ weights and increased organ weight ratios (% body and/or brain weight). Histopathology did not identify abnormalities. Small delays in sexual maturation (preputial separation, vaginal patency) and more Fl rats with prolonged diestrus were also attributable to severely reduced pup body weights. Mating, fertility, sperm parameters, and primordial ovarian follicular counts were unaffected. The no-observable-adverse-effect level (NOAEL) and the reproductive and developmental NOAELs for BDCM were at least 50 ppm (4.1 to 12.6 mg/kg/day), 5125 to 15,750 times the human adult exposure level, if delayed sexual maturational associated with severely reduced body weights is considered reproductive toxicity. If considered general toxicity, reproductive and developmental NOAELs for BDCM are greater than 450 ppm (29.5 to 109.0 mg/kg/day), or 36,875 to 136,250 times the human adult exposure level. Regardless, these data indicate that BDCM should not be identified as a risk to human reproductive performance or development of human conceptuses.

Administration, Oral↗

Computer modeling of human fertility: the impact of reproductive heterogeneity on measures of fertility.

As a result of the paucity of biological markers for both reproductive events and exposure to reproductive toxicants, it is likely that individual members of populations will be misclassified with respect to reproductive performance and xenobiotic exposure. A four-parameter computerized model of fertility (frequency of intercourse, male fecundity, female fecundity, and spontaneous abortion) was developed to explore the effect of misclassification of populations on several measures of fertility. The measures of fertility explored include cumulative percent pregnant, time to pregnancy, cycle specific fertility, and fecundability ratio. The cumulative percent pregnant and time to pregnancy appeared to be insensitive to small changes in reproductive competence. The fecundability ratio decreased in proportion to the size of population exposed to a reproductive toxicant. The three reproductive parameters, time to pregnancy, cumulative percent pregnant, and fecundability, do not appear useful as measures of reproductive heterogeneity in populations. The reproductive heterogeneity of a population was best defined by the change in cycle-specific fertility rate over the period of observation. These simulations suggest that the change in the cycle-specific fertility rate should be evaluated and comparable in all population groups over the period of observation to assure reproductive homogeneity.

Abortion, Spontaneous↗

Development and evaluation of a machine learning model for osteoporosis risk prediction in Korean women.

BACKGROUND: The aim of this study was to develop a machine learning (ML) model for classifying osteoporosis in Korean women based on a large-scale population cohort study. This study also aimed to assess ML model performance compared with traditional osteoporosis screening tools. Furthermore, this study aimed to examine the factors influencing the risk of osteoporosis through variable importance. METHODS: Data was collected from 4199 women aged 40-69 years in the baseline survey of the Ansan and Ansung cohort of the Korean Genome and Epidemiology Study. Osteoporosis was set as the dependent variable to develop ML classification models. Independent variables included 122 factors related to osteoporosis risk, such as socio-demographic characteristics, anthropometric parameters, lifestyle factors, reproductive factors, nutrient intakes, diet quality indices, medical history, medication history, family history, biochemical parameters, and genetic factors. The six classification models were developed using ML techniques, including decision tree, random forest, multilayer perceptron, support vector machine, light gradient boosting machine, and extreme gradient boosting (XGBoost). The six ML classification models were compared with two traditional osteoporosis screening tools, including the osteoporosis risk assessment instrument (ORAI) and the osteoporosis self-assessment tool (OST). The ML model performances were evaluated and compared using the confusion matrix and area under the curve (AUC) metrics. Variable importance was assessed using the XGBoost technique to investigate osteoporosis risk factors. RESULTS: The XGBoost model showed the highest performance out of the six ML classification models, with an accuracy of 0.705, precision of 0.664, recall of 0.830, and F1 score of 0.738. Moreover, the XGBoost model showed a higher performance on AUC than ORAI and OST. Variable importance scores were identified for 69 out of the 122 variables associated with osteoporosis risk factors. Age at menopause ranked first in variable importance. Variables of arthritis, physical activities, hypertension, education level, income level; alcohol intake, potassium intake, homeostatic model assessment for insulin resistance; energy intake, vitamin C intake, gout; and dietary inflammatory index ranked in the top 20 out of the 69 variables, using the XGBoost technique. CONCLUSIONS: This study found that an XGBoost model can be utilized to classify osteoporosis in Korean women. Age at menopause is a significant factor in osteoporosis risk, followed by arthritis, physical activities, hypertension, and education level.

Humans↗

A model of long-term decline in the transmissibility of an infectious disease: implications for the incidence of hepatitis A.

BACKGROUND: The epidemiology of hepatitis A in countries across the world is changing due to improvements in hygiene and living conditions which reduce the transmissibility of the infection. METHODS: A mathematical model is formulated to describe the changes in incidence of a directly transmitted infection produced by a long term decline in its transmissibility. The basic reproduction number, the parameter describing transmissibility, is considered as a function of time. The relationship between the basic reproduction number and the force of infection is derived. RESULTS: Theoretical examples demonstrate that a decline in transmissibility results in an initial decline in the force of infection, but that this may be followed by a substantial resurgence. Resurgences may be possible after several decades of declining incidence, and are most marked following a rapid decline. CONCLUSIONS: Countries which have experienced a rapid decline in the incidence of hepatitis A may be at risk of a resurgence. More detailed mathematical models, informed with data from regular age-stratified serological surveys, should provide the basis for decisions on vaccination policy.

Age Distribution↗

Effects of repeated doses of compound E for 4 and 9 weeks on the male reproductive organs.

Results of two toxicity studies of Compound E, which is an anticancer drug, on male reproductive organs and fertility by oral repeated dosing at dose levels of 12.5, 25 and 50 mg/kg/day for 4 and 9 weeks in rats were compared. After repeated dosing, the male fertility was studied by mating with untreated female animals. At the dose of 50 mg/kg/day in the 4-week study, Compound E significantly decreased testes weight and number of epididymal sperm, caused histopathological changes in the testis and epididymis characterized by decreased germ cells, but did not affect fertility. The dose of 25 mg/kg/day in the 9-week study caused reduction in epididymal weight and number of epididymal sperm and histopathological changes in the testis. The dose of 50 mg/kg/day in the 9-week study was lethal and caused more prominent toxic effects in the reproductive organs and loss of fertility. The present studies suggest that the order of sensitivity of parameters on male reproductive organs is as follows; histopathological examination = organ weight > number of sperm in epididymis > pregnancy index> copulation index. Further, 4-weeks repeated dosing is of sufficient duration to predict adverse effects of test compounds.

Animals↗

An algorithm to predict pregnancy in assisted reproduction.

BACKGROUND: Male fertility potential cannot be measured by conventional parameters for the assisted reproduction technique; ICSI. This study determines the relationship between testicular and ejaculated sperm mitochondrial (mt) DNA deletions, nuclear (n) DNA fragmentation, and fertilization and pregnancy rates in ICSI. METHODS: Ejaculated sperm were obtained from 77 men and testicular sperm from 28 men with obstructive azoospermia undergoing ICSI. Testicular sperm were retrieved using a Trucut needle. mtDNA was analysed using a long PCR. The alkaline Comet assay determined nDNA fragmentation. RESULTS: Of subjects who achieved a pregnancy (50%) using testicular sperm, only 26% had partners' sperm with wild-type (WT) mtDNA. Of pregnant subjects (38%) using ejaculated sperm, only 8% had partner sperm with WT mtDNA. In each, the successful group had less mtDNA deletions and less nDNA fragmentation. There were inverse relationships between pregnancy and mtDNA deletion numbers, size and nDNA fragmentation for both testicular and ejaculated sperm. No relationships were observed with fertilization rates. An algorithm for the prediction of pregnancy is presented based on the quality of sperm nDNA and mtDNA. CONCLUSION: In both testicular and ejaculated sperm, mtDNA deletions and nDNA fragmentation are closely associated with pregnancy in ICSI.

Algorithms↗

[The effect of hyperprolactinemia on biohumoral parameters of bone metabolism in women of reproductive age on chronic hemodialysis].

The study was carried out on a group of 20 women in reproductive age on chronic haemodialysis and on a control group of 11 healthy women. The women on a regular haemodialysis were divided into two subgroups: normoprolactinaemic and hyperprolactinaemic. The following parameters of bone metabolic changes were studied: serum calcium, phosphorus, alkaline phosphatase, pharathormon, osteocalcin, calcitonin, and also LH, FSH, prolactin and estradiol. The values of serum Ca, P, AP, PTH, CTC, OS and of LH and FSH were significantly higher in women on haemodialysis. The hyperprolactinaemic women on haemodialysis had lower values of bone metabolic parameters than normoprolactinaemic women. Hyperprolactinaemia did not significantly contribute to acceleration of bone metabolic changes which were already very accelerated due of secondary hyperparathyroidism.

Adult↗

Toxicological properties of closantel.

The acute, subacute and chronic toxicity studies in laboratory animals showed that closantel is a well tolerated substance. At multiples of the clinical dose, overdosing might result in central nervous system effects and death. Repeated oral dosing was without effects up to 40 mg/kg in rats and dogs except for focal swelling of the epididymis in male rats at 40 mg/kg due to formation of spermatic granulomas. In sheep repeated dosing at 10 and 40 mg/kg orally and at 5 and 20 mg/kg intramuscularly every four weeks during 40 weeks demonstrated an acceptable safety margin in this target species. Reproduction studies including a three-generation study in rats showed that fertility was not affected except slightly in male rats at 40 mg/kg whereas an embryotoxic or teratogenic potential in rats and rabbits was absent. Peri- and postnatal parameters in rats were not affected. In target animals, reproduction was extensively studied in bulls, rams and ewes showing no risk of closantel for reproduction parameters. A mutagenic potential was found to be absent in a Salmonella Ames test, a sex-linked recessive lethal test in Drosophila melanogaster and a dominant lethal test in male and female mice. In 400 mice and 400 rats closantel was shown not to be carcinogenic. Tolerance studies in sheep and cattle demonstrated that oral and parenteral clinical doses were very well tolerated and devoid of serious side-effects.

Administration, Oral↗

What is the most relevant standard of success in assisted reproduction? Is BESST (birth emphasizing a successful singleton at term) truly the best?

There is much variability and no consensus on the definition of the most relevant outcome parameter after assisted reproduction technology (ART). Descriptive reports, such as annual statistics from national registries on the success of ART programmes, should present treatment success in terms of live birth per ovarian stimulation started, as this is the most relevant information for patients and doctors alike. Addressing concerns about the high rate of multiple pregnancies, rescaling the outcome of ART in large programmes and national audits to the singleton, live birth, might trigger a global change of attitude towards elective single embryo transfer in addition to any legal restrictions imposed. For clinical studies, the outcome measure will depend on the hypothesis tested, and investigators should remain free to choose the appropriate primary outcome measure.

Embryo Transfer↗

[An analysis of the interrelation of antilysozyme activity and reproductive function in escherichiae].

In vitro experiments on 72 E. coli strains showed the presence of relationship between the level of their antilysozyme activity and a number of parameters of the reproduction of these bacteria. The factor analysis revealed the integration of the antilysozyme sign with the factors which determined the inhibition of the development of bacterial populations at early stages and controlled the accumulation of bacterial biomass. The study established that the beginning of the expression of the antilysozyme sign of E. coli was associated with the transition of the culture to the phase of slow growth, and the subsequent dynamics of the level of antilysozyme activity was only partially linked with the increase of biomass. The suggestion was made that the antilysozyme factor was one of the elements of the intracellular system regulating the synthesis (and/or stabilization) of peptidoglycan of bacterial cell walls.

Bacteriological Techniques↗

[Recovery of various parameters of the functional state of the reproductive system in thymectomized rats as affected by thymic membrane factor].

Ten-month-old male rats thymectomized in early post-puberty were ascertained to have lower plasma luteinizing and testicular hormones and higher testicular steroid dehydrogenase activity. Following 24 hours of administration of a thymocyte membrane structural agent, pituitary gonadotropic and gonadal androgenic functions became normal. There was no agreement between the hormonal parameters and the levels of nucleic acids in the testes and prostate.

Animals↗

Parameters of humoral and cellular immunity following vaccination of pigs with a European modified-live strain of porcine reproductive and respiratory syndrome virus (PRRSV).

Parameters of humoral and cellular immunity were investigated in pigs experimentally infected with a modified-live European porcine reproductive and respiratory syndrome virus (PRRSV, strain DV). PRRSV was detected by real-time RT-PCR and PRRSV-specific antibodies by a commercial ELISA test-kit, respectively. Interleukins IL-1alpha, IL-2, IL-4, IL-6, IL-8, IL-10, tumor necrosis factor (TNF-alpha) and interferon-gamma (IFN-gamma) as well as IL-2 receptor (IL-2R) were quantified at mRNA level using RT-PCR. Subpopulations of blood lymphocytes were assayed using flow cytometry. No significant changes neither in cytokine expression nor in shifts of CD4 and CD8 markers could be found, but similar curve diagrams concerning CD8 single positive T cells could be observed in all vaccinated animals with an initial decrease and an increase between post-infection days (PIDs) 7 and 14. In the vaccination group, TNF-alpha and IL-6 tended to be increased at PIDs 22 and 40, whereas no increase could be seen in IFN-gamma. When comparing the in vivo immune response to that being seen in in vitro experiments, similar shifts of CD4/CD8 lymphocyte subpopulations may be seen. Cytokine curve diagrams, however, do not reflect the in vitro findings to that extent.

Animals↗

The relative sensitivity of growth and reproduction in the springtail, Folsomia candida, exposed to xenobiotics in the laboratory: an indicator of soil toxicity.

The Folsomia candida reproduction test [ISO, 1998. Soil quality--Inhibition of reproduction of Collembola (Folsomia candida) by soil pollutants. International Standard Organization Report 11267, 1998, Geneva] is used to evaluate the ecotoxicological risks of contaminants in soils. The aim of this study was to compare the sensitivity of growth and reproduction of F. candida to four xenobiotics: two metals (Cd, Al), one metalloid (As), and one organic compound (pentachlorophenol). We showed that reproduction is a slightly more sensitive parameter than growth: EC(20) for reproduction was 1.25 microg/g dry soil for arsenic, 56 microg/g for cadmium, 97.5 microg/g for aluminum, and 41.7 microg/g for pentachlorophenol. The corresponding EC(20) values for growth were 2.8, 65, 630, and 94.6 microg/g. Keeping in mind that a growth test needs fewer juveniles and less time than a reproduction test, we conclude that the two parameters are complementary and could be used for a better ecotoxicological evaluation of contaminants. However, the relative growth and reproduction sensitivities should be tested with more chemicals before growth could be considered as a good alternative for a faster sublethal test.

Aluminum↗

Comparison of the reproductive biology between acaricide-resistant and acaricide-susceptible Rhipicephalus (Boophilus) microplus (Acari: Ixodidae).

The reproductive fitness of Rhipicephalus (Boophilus) microplus (Canestrini) strains resistant to organophosphate (OP), pyrethroid (P), or formamidine (F) acaricides was compared to an acaricide-susceptible (SUS) strain to determine whether the acquisition of resistance affected reproductive fitness in the resistant strains. The SUS strain females had a 3.0 days preoviposition period, a 12.1 days oviposition period, a 22.5 days egg incubation period, a mean of 3670 eggs per female, and a mean percentage egg hatch of 78.1%, which were all remarkably similar to these same parameters reported for this species throughout the world. The reproductive biology of the P-resistant strain (PYR) and the F-resistant strain (FOR) were, for the most part, similar to those of the SUS strain. In the few instances where statistical differences did occur there was little evidence that the variation had any biological basis that could be attributed to a reduction in fitness related to resistance to P or F acaricides. Although the comparison of reproductive parameters of the OP-resistant strain (OPR) and the SUS strain identified statistical differences between the mean egg incubation and oviposition periods, the magnitude of the differences was not sufficient to conclude that the OPR strain was biologically less fit than the SUS strain. However, the OPR strain produced 30% fewer eggs (2562 eggs per female) than the SUS strain (3670 eggs per female) indicating the acquisition of resistance placed the OPR at a selective disadvantage relative to the SUS strain. This coupled with a lower, though non-significant, egg hatch was used to predict there would be a reduction of at least 34.1% in larval numbers available to potentially re-infest subsequent cattle than were available from the SUS strain. These data may aid the development of management strategies that can be used to control OP-resistant ticks.

Amidines↗