Stress in Parents of Children With Genetically Determined Leukoencephalopathies: A Pilot Study.

Genetically determined leukoencephalopathies comprise a group of rare inherited white matter disorders. The majority are progressive diseases resulting in early death. We performed a cross-sectional pilot study including 55 parents from 36 families to assess the level of stress experienced by parents of patients with genetically determined leukoencephalopathies, aged 1 month to 12 years. Thirty-four mothers and 21 fathers completed the Parenting Stress Index-4th Edition. One demographic questionnaire was completed per family. Detailed clinical data was gathered on all patients. Statistical analysis was performed with total stress percentile score as the primary outcome. Mothers and fathers had significantly higher stress levels compared with the normative sample; 20% of parents had high levels of stress whereas 11% had clinically significant levels of stress. Mothers and fathers had comparable total stress percentile scores. We identified pediatric behavioral difficulties and gross motor function to be factors influencing stress in mothers. Our study is the first to examine parental stress in this population and highlights the need for parental support early in the disease course. In this pilot study, we demonstrated that using the Parenting Stress Index-4th Edition to assess stress levels in parents of patients with genetically determined leukoencephalopathies is feasible, leads to valuable and actionable results, and should be used in larger, prospective studies.

Successful in vitro maturation of oocytes in a woman with gonadotropin-resistant ovary syndrome associated with a novel combination of FSH receptor gene variants: a case report.

Infertility due to Gonadotropin-Resistant Ovary Syndrome (GROS) is a rare type of hypergonadotropic hypogonadism. Here, we report an original case of GROS, associated with compound heterozygous follicle-stimulating hormone receptor (FSHR) variants, in a woman who achieved a live birth by in vitro maturation (IVM) of her oocytes. This 31-year-old woman consulted our assisted reproduction center for a second opinion after having been advised, because of pervasive high serum follicle-stimulating hormone (FSH) levels, to pursue in vitro fertilization (IVF) with donor oocytes. She presented with primary infertility and progressively prolonged menstrual cycles. Her serum FSH levels were indeed found to be high, but in discordance with a normal anti-Müllerian hormone (AMH) level and antral follicle count. Genetic investigation found the patient to be compound heterozygous for two FSHR variants: I160T, a known pathologic variant, and N558H, which has never been previously reported. As there was no ovarian response to high daily doses of exogenous gonadotropins, IVM was proposed to the patient with success and she finally delivered at term a healthy boy. Effects of the receptor variants were analyzed in heterologous cells. Whereas the I160T mutation blocked FSHR membrane trafficking and FSH-stimulated cAMP-dependent signaling in transfected CHO cells, the novel variant, N558H, functioned equivalently to wild-type FSHR in the assays employed. In conclusion, IVM should always be offered as a first-line therapy to infertile women presenting with GROS. The N558H variant discovered in FSHR is novel, but its functional significance, if any, is unresolved and merits further investigation as it may be associated with a recessive FSHR-related disorder.

Acantholytic folliculitis and epidermitis associated with Staphylococcus hyicus in a line of white Leghorn laying chickens.

Several mature Leghorn-type hens with the same genetic background experienced skin and feather problems in a breeder flock. There was almost-total feather loss on the head and neck, as well as thickened, scaly skin, and follicular ostia were plugged with keratin debris. Other individuals exhibited prominent subcutaneous nodules multifocally on the head. Histologic examination of the skin revealed a severe hyperplasia of follicular epithelium with hyperkeratosis and cystic dilation. Numerous clefts and vesicles were detected along the epidermis and follicular epithelium, some containing acantholytic keratinocytes. A mild heterophilic inflammation was associated with these lesions, and few gram-positive cocci were present in the keratin plugs. Bacterial culture of the skin yielded a variable amount of Staphylococcus hyicus. Immunochemistry looking for chicken IgY revealed no intercellular staining in the epidermis or follicular epithelium. All these findings supported a diagnosis of Staphylococcus-associated acantholytic epidermitis and folliculitis. This case suggests that S. hyicus could be a significant pathogen in poultry production. The close genetic relationship among affected individuals could indicate a hereditary predisposition in this line of White Leghorn laying chickens.

Host response to various treatments to reduce Salmonella infections in swine.

Host response was evaluated following the administration of various treatments, such as probiotics, prebiotics, and vaccination, to reduce Salmonella in swine. Response to the treatments were studied by the evaluation of phagocytosis rates by flow cytometry, by studying the activation of whole-blood phagocytes by bioluminescence, the production of IgA against S. Typhimurium, and by histopathology. Significant differences were observed in the activation of whole-blood phagocytes in all groups of treated pigs (P = 0.0001). In SC54 vaccinated pigs, a significant reduction of Salmonella in the ileum was observed (P < 0.05) and the production of IgA against S. Typhimurium was higher in this group in comparison to uninfected control pigs (P = 0.0007). Furthermore, significant histopathological (P < 0.05) changes were observed in SC54 vaccinated pigs. Villus height and mucus and goblet cells density in the small intestine were reduced in vaccinated pigs in comparison to infected control pigs. Taken together, these findings suggest that SC54 vaccine can stimulate local immunity and reduce the presence of Salmonella in the ileum in swine. Use of SC54 vaccine should thus be considered in further field experiments.

Presence of Yersinia enterocolitica in tissues of orally-inoculated pigs and the tonsils and feces of pigs at slaughter.

In order to study the early events associated with infection of swine by Yersinia enterocolitica, 42 five-week-old crossbred piglets were inoculated per os with approximately 10(8) Y. enterocolitica O:3. Groups of 5 animals (and one negative control) were euthanized 30 min, 3, 6, 12, 24, 48 and 72 h following the infection. Palatine tonsils, retropharyngeal and mesenteric lymph nodes, esophagus, duodenum, jejunum, ileum (and Peyer's patches), stomach, liver, spleen and feces (from colon) were collected and analyzed for the presence of Y. enterocolitica by standard bacteriological procedures. Natural infections were also analyzed, as a complementary study, by taking one-gram samples of fecal material and tonsils from 291 pig carcasses less than 3 h after slaughter and culturing them for Y. enterocolitica using a cold enrichment technique. Within 30 min, Yersinia enterocolitica O:3 was already present at most sites. The presence of Y. enterocolitica in the liver of 3 out of 10 animals and also in the spleen of 3 out of 10 piglets, within the first 3 h postinfection, but not at later times (with one exception), probably indicated a transient bacteremia accompanying the initial stages of infection. The tonsils were colonized in most animals (13/20) as the bacteria remained present from 12 to 72 h postinfection, while only 4 out of 20 fecal samples were found to be positive over the same period. Up to 10(4) colony-forming units of Y. enterocolitica per gram of tonsil and fecal material were recovered. Finally, among the 291 animals sampled at the abattoir, a total of 79 were found positive, 70 of the tonsils sampled were positive, and bacteria were recovered in 17 fecal samples. It is therefore suggested that palatine tonsils are the most reliable tissue for the indication of an infection/colonization by Y. enterocolitica O:3 in swine and that the removal of this tissue during the slaughter process should be considered in order to minimize the possibility of contamination of meat products.

Oral malignant melanoma with osteoid formation in a dog.

Melanomas are the most frequent malignant neoplasms of the oral cavity of dogs. Osteogenic melanoma is a rare variant of melanoma that has been described in humans but not in animals. We describe a case of malignant melanoma with bone production affecting the gingiva of a 12-year-old Miniature Dachshund dog. The tumor was a round, lightly pigmented mass that measured 1 cm in diameter and was hard to cut. Histologically, the tumor was composed of nests and lobules of anaplastic, round, melanin-containing cells supported by a stroma displaying abundant osteoid matrix. Many of the neoplastic melanocytic cells were in close contact with the osteoid trabeculae. Immunohistochemical tests revealed that the neoplastic cells were immunoreactive for S-100 and vimentin and showed no staining with cytokeratin. The animal had a local recurrence of the tumor 3 months after the initial excision. This is the first case of malignant melanoma with osteoid formation reported in animals.

Focal symmetrical encephalomalacia in a 6-month-old Dorset sheep.

Neurological examination of a sheep that had acute onset of recumbency and mental depression indicated a diffuse symmetrical thalamocortical lesion. Cerebrospinal fluid analysis suggested a degenerative central nervous system disease. Thiamin administration resulted in partial and temporary improvement. Brain histological lesions were typical of focal symmetrical encephalomalacia.

P-selectin expression in canine cutaneous inflammatory diseases and mast cell tumors.

P-selectin, a member of the selectin family of adhesion molecules, mediates the initial adhesion of leukocytes to the blood vessel wall during their emigration from the circulation. Adhesion molecules play an important role in the pathogenesis of several diseases, including various skin conditions. The objectives of the present study were to characterize the expression of vascular P-selectin in the skin of dogs suffering from inflammatory diseases or from common cutaneous neoplasms, and to determine if a correlation exists between P-selectin expression and inflammatory cell infiltration in these conditions. Immunohistochemistry was performed on formalin-fixed canine skin using a specific anti-canine P-selectin monoclonal antibody (MD3). Results showed that P-selectin was minimally expressed in normal canine skin. However, the number of P-selectin-expressing blood vessels was significantly increased (P < 0.05) in cases of allergic dermatitis, autoimmune dermatitis, pyogranulomatous dermatitis, dermatophytosis, and panniculitis. Highest P-selectin expression (percentage of MD3-positive vessels and intensity of the reaction) was observed in cases of autoimmune and pyogranulomatous dermatitis (55.3+/-7.4 and 44.0+/-9.9% P-selectin-positive vessels, respectively). In all conditions studied, a positive correlation existed between the number of P-selectin-positive blood vessels and the number of infiltrating leukocytes (r=0.556, P < 0.01). A significant number of blood vessels in mast cell tumors also expressed P-selectin, whereas no staining was observed in any of the histiocytomas examined. These results reveal that P-selectin expression is increased in different types of canine inflammatory skin diseases and suggest that P-selectin could participate in the local recruitment of leukocytes in canine cutaneous diseases.