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In the past two decades, the potential association between the risk of suicidal ideation and behavior and the clinical use of pharmaceutical products has been debated among industry, regulators, and academia. A better understanding of the possible effects-favorable, unfavorable, or neutral-of pharmaceuticals on the risk of suicidal ideation and behavior may be required, especially for trials typically designed for other primary objectives. Here, a cross-industry statistical team provides recommendations that address the assessment, statistical analysis, interpretation, and utility of suicide-related data in pharmaceutical clinical trials. These recommendations are to evaluate suicidal ideation, suicidal behavior, and the two combined as end points; utilize standard scales to collect data prospectively; and analyze the data using several statistical methods. A more accurate assessment of the potential association between the use of pharmaceutical products and risk of suicide-related events will contribute to estimating the benefit/risk ratio and result in safer medicines for patients.

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Clinical toxoplasmosis in chickens (Gallus domesticus) has been rarely reported in literature. Here we report that three chickens on a farm in Illinois developed neurological signs. One of these chickens was examined postmortem and it had non-suppurative encephalitis with numerous Toxoplasma gondii tachyzoites and tissue cysts. The identity of the protozoa was confirmed immunohistochemically by staining with T. gondii specific antibodies, and by transmission electron microscopy. The owner of the 3 chickens donated all 11 remaining chickens and a goose on his property for the present study. All 11 chickens and a goose were euthanized, and blood, heart, brain, and 1 leg were obtained for T. gondii examination. Antibodies to T. gondii were found in sera of all chickens with titers of 1:40 in one, 1:320 in three, and 1:640 or higher in seven chickens tested by the modified agglutination test (MAT). The goose had a MAT titer of 1:320. For isolation of T. gondii, whole heart and brain and 50 g of leg muscles were digested in an acid-pepsin solution and bioassayed in four mice for each tissue. Viable T. gondii was isolated from tissues of all 11 chickens and the goose. Genotyping of these 12 T. gondii isolates using polymorphism at the genetic loci SAG1, SAG2, SAG3, BTUB, GRA6, c22-8, c29-2, L358, PK1, a new SAG2 and Apico revealed that all isolates had Type II alleles at all loci, indicating these T. gondii isolates belong to the predominant clonal Type II lineages. This is the first report of isolation of viable T. gondii from a domestic goose (Anser anser).

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FoxP2 is the first identified gene that is specifically involved in speech and language development in humans. Population genetic studies of FoxP2 revealed a selective sweep in recent human history associated with two amino acid substitutions in exon 7. Avian song learning and human language acquisition share many behavioral and neurological similarities. To determine whether FoxP2 plays a similar role in song-learning birds, we sequenced exon 7 of FoxP2 in multiple song-learning and nonlearning birds. We show extreme conservation of FoxP2 sequences in birds, including unusually low rates of synonymous substitutions. However, no amino acid substitutions are shared between the song-learning birds and humans. Furthermore, sequences from vocal-learning whales, dolphins, and bats do not share the human-unique substitutions. While FoxP2 appears to be under strong functional constraints in mammals and birds, we find no evidence for its role during the evolution of vocal learning in nonhuman animals as in humans.

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This paper describes acute visceral and neural sarcocystosis in four dogs. One animal was simultaneously infected with distemper virus, and another with Blastomyces dermatitidis. Schizonts and merozoites of Sarcocystis canis were found in the lesions. 1999 W.B. Saunders and Company Ltd.

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A novel virus, designated swine hepatitis E virus (swine HEV), was identified in pigs. Swine HEV crossreacts with antibody to the human HEV capsid antigen. Swine HEV is a ubiquitous agent and the majority of swine >/=3 months of age in herds from the midwestern United States were seropositive. Young pigs naturally infected by swine HEV were clinically normal but had microscopic evidence of hepatitis, and developed viremia prior to seroconversion. The entire ORFs 2 and 3 were amplified by reverse transcription-PCR from sera of naturally infected pigs. The putative capsid gene (ORF2) of swine HEV shared about 79-80% sequence identity at the nucleotide level and 90-92% identity at the amino acid level with human HEV strains. The small ORF3 of swine HEV had 83-85% nucleotide sequence identity and 77-82% amino acid identity with human HEV strains. Phylogenetic analyses showed that swine HEV is closely related to, but distinct from, human HEV strains. The discovery of swine HEV not only has implications for HEV vaccine development, diagnosis, and biology, but also raises a potential public health concern for zoonosis or xenozoonosis following xenotransplantation with pig organs.

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Spirochetes similar to those described in the ceca of broilers with diarrhea and in laying hens with decreased egg production and growth were identified in the ceca of captive-raised juvenile ring-necked pheasants (Phasianus colchicus). The birds were submitted for diagnostic investigation of an illness characterized by a seromucoid ocular discharge, sneezing, swollen infraorbital sinuses, and weight loss. In addition to cecal spirochetosis, the birds had mild enteric coccidiosis, trichomoniasis, and nematodiasis (Heterakis spp.); esophageal capillariasis; and respiratory mycoplasmosis. Weakly beta-hemolytic spirochetes isolated from the ceca of one pheasant were identified as Serpulina pilosicoli with the use of a 16S rRNA sequence-specific polymerase chain reaction amplification assay. Diffuse cecal enterocyte attachment was reproduced in a 1-day-old chick challenged with the pheasant S. pilosicoli isolate. Immunohistochemical staining of sections of ceca from the pheasant and challenged chick with a Serpulina spp. flagellar antigen-specific monoclonal antibody confirmed spirochetal attachment to cecal enterocytes. The etiologic significance of the spirochete infection is unknown because respiratory signs and multiple gastroenteric pathogens dominated the clinicopathologic manifestations and an intestinal disorder was not a clinical complaint.

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Resistance to the soybean cyst nematode (SCN) (Heterodera glycines Ichinohe) is difficult to evaluate in soybean [Glycine max (L.) Merr.] breeding. PI 437.654 has resistance to more SCN race isolates than any other known soybean. We screened 298 F6∶7 recombinant-inbred lines from a cross between PI 437.654 and 'BSR101' for SCN race-3 resistance, genetically mapped 355 RFLP markers and the I locus, and tested these markers for association with resistance loci. The Rhg 4 resistance locus was within 1 cM of the I locus on linkage group A. Two additional QTLs associated with SCN resistance were located within 3cM of markers on groups G and M. These two loci were not independent because 91 of 96 lines that had a resistant-parent marker type on group G also had a resistant-parent marker type on group M. Rhg 4 and the QTL on G showed a significant interaction by together providing complete resistance to SCN race-3. Individually, the QTL on G had greater effect on resistance than did Rhg 4, but neither locus alone provided a degree of resistance much different from the susceptible parent. The nearest markers to the mapped QTLs on groups A and G had allele frequencies from the resistant parent indicating 52 resistant lines in this population, a number not significantly different from the 55 resistant lines found. Therefore, no QTLs from PI 437.654 other than those mapped here are expected to be required for resistance to SCN race-3. All 50 lines that had the PI 437.654 marker type at the nearest marker to each of the QTLs on groups A and G were resistant to SCN race-3. We believe markers near to these QTLs can be used effectively to select for SCN race-3 resistance, thereby improving the ability to breed SCN-resistant soybean varieties.

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Cuphea lanceolata Ait. has had a significant role in the domestication of Cuphea and is a useful experimental organism for investigating how medium-chain lipids are synthesized in developing seeds. To expand the genetics of this species, a linkage map of the C. lanceolata genome was constructed using five allozyme and 32 restriction-fragment-length-polymorphism (RFLP) marker loci. These loci were assigned to six linkage groups that correspond to the six chromosomes of this species. Map length is 288 cM. Levels of polymorphism were estimated for three inbred lines of C. lanceolata and an inbred line of C. viscosissima using 84 random genomic clones and two restriction enzymes, EcoRI and HindIII. Of the probes 29% detected RFLPs between C. lanceolata and C. viscosissima lines. Crosses between these species can be exploited to expand the map.

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Furazolidone induces a cardiotoxicosis when fed in toxic concentrations to newly hatched ducklings. This preliminary experiment was designed to determine if creatine kinase (CK) isoenzymic activities or other serum analytes would be useful as indicators of these cardiac alterations. Sera from 12 ducklings (six fed a control ration and six fed the control ration with 700 mg furazolidone added per kg of feed [700 ppm] for 28 days) were analyzed for CK isoenzymic activities, electrolytes, nitrogenous metabolites, hepatic enzymic activities, bilirubin, and glucose. Statistically significant differences between control and treated groups were detected for creatine kinase MB (CK-MB, cardiac muscle origin) isoenzymic activity and bilirubin, potassium, calcium, and total carbon dioxide concentrations. Differences other than CK-MB isoenzymic activity were generally explained by factors related to the toxicosis or sample handling. These findings suggest that CK-MB isoenzymic activity may be useful to detect and monitor the progress of cardiac injury in furazolidone toxicosis, thereby increasing the usefulness of this model of dilated cardiomyopathy. Our findings, analyzed on the Kodak Ektachem 700 Dry Chemistry Analyzer, are compared with serum chemistry values reported in the literature.

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Clinical and pathologic alterations during the development of furazolidone-induced toxicosis were investigated in a group of 35 newly hatched male Pekin ducklings fed a ration containing 700 mg of furazolidone/kg of feed for 27 days. A control group (n = 25) was fed the same ration without added furazolidone. Every 3 days, ducklings were weighted and palpated for ascites and 3 were chosen at random for euthanasia to determine the severity of lesions and to obtain hearts for gross measurements and ultrastructural study. Clinical alterations in treated ducklings consisted of decreased feed consumption with lower weight gain and nervous signs. Gross pathologic alterations included cardiomegaly with dilatation of all chambers and thinning of the myocardium, pericardial effusion, pulmonary edema and congestion, ascites, and testicular enlargement. Gross lesions were not observed before day 8. The earliest lesion (day 9) was cardiac chamber dilatation, with the left ventricle and left atrium most commonly and most severely dilated. Hearts from ducklings euthanatized on days 6, 12, 18, 24, and 27 were examined ultrastructurally. Myofibrillar lysis was first observed on day 12 in 1 duckling (of 3) and in at least 1 duckling from subsequent euthanasia periods. Myofibrillar lysis did not appear to be uniform among the cardiac chambers.

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Furazolidone cardiotoxicosis was induced in 2 groups (FZ and FZ-CR groups) of newly hatched male Pekin ducklings (100/group) by feeding a ration containing 650 mg of furazolidone/kg of feed (ppm) for 28 days. A third group (control ration, CR group; n = 100) was fed the same ration without furazolidone. On day 28, the control ration was initiated for the FZ-CR group initially given the furazolidone-containing ration, to allow recovery from the effects of the drug, whereas ducklings of the FZ group continued to consume the furazolidone-containing ration. Biweekly, beginning with week 4, ducklings were euthanatized to assess severity of gross lesions and to obtain sections of myocardium for histologic and ultrastructural examination. Clinical evidence (increased weight gain, increased feed consumption, decreased mortality, reduced prevalence of palpable ascites) of regression of cardiotoxicosis of ducklings of the FZ-CR group was nearly complete by day 56 (28 days after cessation of furazolidone intake). Likewise, regression of gross lesions, as measured by overall prevalence of gross lesions, left ventricular volume, and ascites prevalence and severity, were also essentially complete by day 56. Myofibrillar lysis was not seen in sections from the heart (examined ultrastructurally) obtained from ducklings of the CR group that were euthanatized on day 28, 56, or 98. Myofibrillar lysis was detected in all ducklings (4/4) fed furazolidone (FZ and FZ-CR groups) and euthanatized on day 28. Myofibrillar lysis was not seen in the heart of ducklings of the FZ-CR group that were euthanatized on day 56 or 98. Myofibrillar lysis was detected in the heart from all ducklings of the FZ group that were euthanatized on day 56.(ABSTRACT TRUNCATED AT 250 WORDS)

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