Extended genotypic evaluation and comparison of twenty-two cases of lethal EEHV1 hemorrhagic disease in wild and captive Asian elephants in India.

Thirteen new lethal cases of acute hemorrhagic disease (HD) with typical histopathogical features were identified in young Asian elephants (Elephas maximus indicus) in India between 2013 and 2017. Eight occurred amongst free-ranging wild herds, with three more in camp-raised orphans and two in captive-born calves. All were confirmed to have high levels of Elephant Endotheliotropic Herpesvirus type 1A (EEHV1A) DNA detected within gross pathological lesions from necropsy tissue by multi-locus PCR DNA sequencing. The strains involved were all significantly different from one another and from nine previously described cases from Southern India (which included one example of EEHV1B). Overall, eight selected dispersed PCR loci totaling up to 6.1-kb in size were analyzed for most of the 22 cases, with extensive subtype clustering data being obtained at four hypervariable gene loci. In addition to the previously identified U48(gH-TK) and U51(vGPCR1) gene loci, these included two newly identified E5(vGPCR5) and E54(vOX2-1) loci mapping far outside of the classic EEHV1A versus EEHV1B subtype chimeric domains and towards the novel end segments of the genome that had not been evaluated previously. The high levels of genetic divergence and mosaic scrambling observed between adjacent loci match closely to the overall range of divergence found within 45 analyzed North American and European cases, but include some common relatively unique polymorphic features and preferred subtypes that appear to distinguish most but not all Indian strains from both those in Thailand and those outside range countries. Furthermore, more than half of the Indian cases studied here involved calves living within wild herds, whereas nearly all other cases identified in Asia so far represent rescued camp orphans or captive-born calves.

A model for predicting performance on the NBME Part I examination.

Multiple regression analyses were employed to determine the relationships between achievement variables as predictors of the performance on Part I of the National Board of Medical Examiners examinations (NBME-I) of 366 medical students. The students' examination score averages in first- and second-year basic science courses were sequentially added to a composite Medical College Admission Test (MCAT) score to investigate the increases in prediction accuracy. Four prediction equations were cross validated on two subsequent medical school classes. While the multiple correlation between the predicted NBME-I score and the actual score significantly increased as first- and second-year course examination scores were added to the equations, the overall accuracy in predicting passing or failing did not substantially increase. The most useful equation employed a combination of the MCAT score and the first semester anatomy course examination score. The NBME-I predictions were given by letter to the 1984 and 1985 students approximately a year before they were to take the NBME-I examination so that students at risk of failure could undertake remedial study.

Craniofacial, caudal, and visceral anomalies associated with mutant sirenomelic mice.

Craniofacial anomalies were correlated with mutant murine sirenomelia. Ninety-eight newborn sirens from heterozygous matings were examined and analyzed. In the 96 sirens that had intact craniofacial structures, micrognathia was seen in 39% of the sirens, microstomia in 34%, macroglossia in 26%, and cleft palate in 21%. Even when not cleft, the siren palates were narrower and more highly arched than those of nonsiren littermates. The frequency of abnormal craniofacial development was greater in those sirens that were more severely affected caudally. Even though some earlier studies had indicated a preponderance of males, 46 of the 95 sirens with intact pelvic viscera were females. Fifty-three percent of the sirens were monopodal, 35% were apodal, and 11% were dipodal. A penile-like projection on the genital tubercle occurred on 15 apodal sirens and four monopodal sirens; all but three of these sirens were males. Bladder agenesis was seen in 100% of the sirens, anal atresia in 80%, and bilateral renal agenesis in 43%. No siren was found with bilaterally normal kidneys. The srn gene responsible for sirenomelia might either directly affect the embryo at both the caudal and cranial regions or indirectly affect the embryo by producing lateral mechanical compression at both these sites. The srn gene was earlier characterized as autosomal-recessive; our data confirm this. Sirenomelia was found in only 11% of the newborns from crosses of carrier mice in the colony. Analyses of uterine contents at days 12-14 suggest that the srn gene is fully penetrant, but often lethal, during the fetal period.

Normal and abnormal midfacial development in the cadmium-treated hamster.

Clefts of the midface ranging in severity from a notched lip to complete facial disorganization were observed in the offspring of golden hamsters injected with cadmium chloride on the morning of the eighth day of gestation. Other malformations frequently observed were microphthalmia, anophthalmia, and diencephalic encephaloceles. Histologic examination of embryos on the 10th, 11th, 12th, and 13th days of gestation revealed a marked deficiency of mesenchyme in the frontonasal process, which led to a foreshortened and deformed nasal septum. These data confirm that the teratogenicity of cadmium is highly specific for the region of the anterior neural segment on the eighth day of gestation. The deficiency of mesenchyme in the frontonasal process may be the result of disruption in neural crest cell development in this region.

The effects of altering the pH of seminal fluid on the sex ratio of rabbit offspring.

It has been suggested that the pH of the vagina at the time of fertilization may have a differential effect on X- or Y-bearing sperm and thereby affect the sex of the offspring. To test this postulate, rabbit semen was collected, diluted 1:10 with a buffer of pH 5.4, 6.9, or 9.6, and after 20 minutes 0.5 ml of semen-buffer mixture was used for insemination in an ovulation-induced female. Newborn pups were examined both externally and internally for gender. The females inseminated with acidic semen had 6 litters, 50 offspring, with 48% males; those with neutral semen had 8 litters, 48 offspring, with 63% males; and those with alkaline semen had 7 litters, 49 offspring, with 49% males. There was no significant difference in these sex ratios from the expected 50% males. Motility of rabbit sperm at 23 degrees C in buffers of pH 4.6, 5.4, 6.9, 9.6, and 9.8 was reduced in vitro as the pH deviated from neutrality. Acid conditions were more detrimental than alkaline conditions. Sperm lost their motility more quickly in buffers of 37 degrees C than in buffers of 23 degrees C. It was not possible with scanning electron microscopy to distinguish morphologically between X- and Y-bearing sperm. It seems unlikely that a direct effect of pH on sperm can be a single influence on the sex of offspring.

Tolbutamide treatment of pregnant mice: repeated administration reduces fetal lethality.

Pretreatment of pregnant BALB/c mice with several low doses of tolbutamide protected against the fetolethal effects of a high dose. Pregnant mice were given single ip injections of 400 mg/kg in saline on day 13; 100 mg/kg/day on days 10, 11, 12, and 13; or 100 mg/kg/day on days 10, 11, and 12 and 400 mg/kg on day 13. On day 16 the single-treatment group had a significantly higher resorption rate than any other group. Fetolethality was not related to hypoglycemia. The protective effect of pretreatment may have been due to induction of maternal microsomal enzymes.