Characterization of an Inherited Neurologic Syndrome in Toyger Cats with Forebrain Commissural Malformations, Ventriculomegaly and Interhemispheric Cysts.

BackgroundIn children, frequent congenital malformations with concomitant agenesis of the corpus callosum are diagnosed by neuroimaging in association with other cerebral malformations, including interhemispheric cysts and ventriculomegaly. Similar studies providing full characterization of brain defects by in vivo magnetic resonance imaging (MRI), and correlations with the pertinent anatomic pathologic examinations are absent in veterinary medicine.Hypothesis/objectivesCongenital brain defects underlie the neurologic signs observed in Toyger cats selectively bred for a short ear phenotype.AnimalsUsing proper pedigree analysis and genetic evaluations, 20 related Oriental-derived crossbred Toyger cats were evaluated. Seven clinically healthy (carrier) cats and 13 clinically affected cats that had neurologic signs, short ear phenotype and concomitant complex brain anomalies were studied.MethodsComplete physical and neurologic examinations and MRI were performed in all clinically healthy and affected cats. Postmortem and histopathologic examinations were performed in 8 affected cats and 5 healthy cats.ResultsNeurologic and MRI investigations confirmed 13 clinically affected cats with structural brain abnormalities. Ventriculomegaly with frequent concomitant supratentorial interhemispheric, communicating ventricular type-1b cysts and multiple midline and callosal malformations were detected in all cats displaying neurologic signs. Genetic analysis confirmed autosomal recessive mode of inheritance with no chromosomal abnormalities.Conclusions and clinical importanceNeuroanatomic dissections and histopathology were helpful for evaluation of abnormalities in midline brain structures, and for the full characterization of cysts. However, MRI was more sensitive for detection of small cysts. In this feline model, MRI diagnosis had extremely good correlation with pathologic abnormalities noted in the subset of animals that were examined by both modalities

Adult onset thalamocerebellar degeneration in dogs associated to neuronal storage of ceroid lipopigment

Late onset of hereditary cerebellar cortical abiotrophy has been described in a large variety of canine breeds. In some reported conditions, the cerebellar lesion is combined with degeneration of other systems. Here we describe a new hereditary cerebellar cortical degeneration in eight adult American Staffordshire and Pit Bull Terriers. The neuronal degeneration in these animals not only affects Purkinje cells of the cerebellum but also certain thalamic nuclei. In addition, nerve cell loss appears to be associated with a lysosomal storage disease, which is restricted to the affected cell populations. The stored material was histologically and ultrastructurally identified as fluorescent lipopigment. Since animals were euthanized at various stages of the disease, it could be shown that lysosomal storage preceded neuronal loss. Selective involvement of restricted neuronal populations is highly unusual in ceroid lipofuscinoses. It remains to be determined if the present neurodegenerative disease is caused by a primary or secondary neuronal ceroid lipofuscinosi

Case Report : Neuroblastoma-Like Schwannoma in a Domestic Short-Haired Cat

An axillary mass was detected in a 6-year-old, neutered, male, domestic short-haired cat during a wellness exam. Gross examination following surgical removal revealed a discrete, deep subcutaneous, discoid mass that was between 0.5- and 0.7-cm-in-diameter and diffusely firm and white. Histologically, the mass was well-demarcated, partially encapsulated, and expanded the panniculus carnosus. It was composed of tightly packed, giant rosettes of radially arranged fusiform cells stacked in one to 10 layers with peripherally palisading nuclei and with centrally oriented, fibrillary, cytoplasmic processes, and collagenous fibers. Laminin immunoreactivity and ultrastructural examination highlighted a continuous basal lamina outside the plasma membrane of each neoplastic cell. Neoplastic cells were immunoreactive for GFAP, S100, periaxin, and Sox-10 and were immunonegative for synaptophysin, smooth muscle actin, and pancytokeratin. Collective findings were consistent with a diagnosis of neuroblastoma-like schwannoma. This is the first veterinary report of this rare variant of benign schwannoma

Variability in disease phenotypes within a single PRNP genotype suggests the existence of multiple natural sheep scarpie strains within Europe

Variability of pathological phenotypes within classical sheep scrapie cases has been reported for some time, but in many instances it has been attributed to differences in the PRNP genotype of the host. To address this issue we have examined by immunohistochemistry (IHC) and Western blotting (WB) for the disease-associated form of the prion protein (PrPd), the brains of 23 sheep from five European countries, all of which were of the same ARQ/ARQ genotype. As a result of IHC examinations, sheep were distributed into five groups with different phenotypes and the groups were the same regardless of the scoring method used, ‘long’ or ‘short’ PrPd profiling. The groups made did not respond to the geographical origin of the cases and did not correlate with the vacuolar lesion profiles, which showed a high individual variability. Discriminatory IHC and WB methods coincided to detect a ‘CH1641-like’ case but otherwise correlated poorly in the classification of disease phenotypes. No other polymorphisms of the PRNP gene were found that could account for the pathological differences, except perhaps for a sheep from Spain with a mutation at codon 103 and a unique pathological phenotype. Preliminary evidence indicates that those different IHC phenotypes correlate with distinct biological properties on bioassay, suggesting that they are indicative of strain diversity. We therefore conclude that natural scrapie strains exist and that they can be revealed by detailed pathological examinations, which can be harmonized between laboratories to produce comparable results

Un nuevo medidor de flujo de alta presión para la estimación de la resistencia hidráulica en brotes completos de plantas leñosas

A new high-pressure flowmeter has been developed and used to estimate hydraulic resistance in whole shoots of woody plants. It is based on the perfusion of pressurized water in the plant, and the simultaneous measurement of water flow (introduced volume of water per unit of time). This device was first calibrated, and then used to estimate the hydraulic resistance of stems and leaves in 1-yr seedlings of broadleaf Quercus species (Q. rubra, Q. cerris, Q. velutina, Q. petraea, Q. frainetto, Q. pyrenaica). The measured values are reliable and similar to those reported in the literature, but taking into account that this study dealt with seedlings. We have found significant differences between species and groups of species according to their hydraulic resistance values for stems and leaves. Those species whose seedlings showed lower leaf hydraulic resistance values can rehydrate their leaves more quickly and survive in environments with certain water stress (e.g., Q. pyrenaica). The high leaf hydraulic resistance of other species indicate that they can not resist these levels of water stress (e.g, Q. rubra). This study provided new insight to the importance of leaf hydraulic resistance as an adaptative trait to face water stress. Hydraulic resistance variability must be studied in depth as an additional mechanism within a wide array of morphological and ecophysiological adaptations that provide tree species a greater drought tolerance.Se ha desarrollado y utilizado un nuevo medidor de flujo de alta presión para plantas leñosas. Su principio de funcionamiento consiste en perfundir agua a presión a través de la planta y, simultáneamente, medir el flujo del líquido (volumen de agua introducida en la planta por unidad de tiempo). Este dispositivo ha sido primero calibrado y después empleado para estimar la resistencia hidráulica de tallos y hojas de plántulas de especies no esclerófilas del género Quercus (Q. rubra, Q. cerris, Q. velutina, Q. petraea, Q. frainetto, Q. pyrenaica). Los valores obtenidos son fiables y comparables a los de la literatura pero teniendo en cuenta que se han estudiado plántulas. Se han encontrado diferencias significativas entre especies y grupos de especies en cuanto a la resistencia hidráulica de hojas y tallos. Las especies cuyas plántulas muestran menor resistencia hidráulica de hojas pueden rehidratarlas de forma más rápida y así sobrevivir en medios con cierto estrés hídrico como los mediterráneos (p. ej. Q. pyrenaica). La elevada resistencia hidráulica de las hojas de otras especies indica que éstas no podrán soportar este estrés hídrico (p. ej. Q. rubra). Se ha puesto de manifiesto la importancia de la resistencia hidráulica foliar como adaptación frente al estrés hídrico. Debe profundizarse en el estudio de la variabilidad de la resistencia hidráulica como un mecanismo adicional dentro del amplio conjunto de adaptaciones morfológicas y ecofisiológicas que confieren a las especies arbóreas mayor tolerancia frente a la sequía

Effects of sardine-enriched diet on metabolic control, inflammation and gut microbiota in drug-naïve patients with type 2 diabetes: a pilot randomized trial.

Nutrition therapy is the cornerstone of treating diabetes mellitus. The inclusion of fish (particularly oily fish) at least two times per week is recommended by current international dietary guidelines for type 2 diabetes. In contrast to a large number of human studies examining the effects of oily fish on different cardiovascular risk factors, little research on this topic is available in patients with type 2 diabetes. The aims of this pilot study were to investigate the effects of a sardine-enriched diet on metabolic control, adiponectin, inflammatory markers, erythrocyte membrane fatty acid (EMFA) composition, and gut microbiota in drug-naïve patients with type 2 diabetes. 35 drug-naïve patients with type 2 diabetes were randomized to follow either a type 2 diabetes standard diet (control group: CG), or a standard diet enriched with 100 g of sardines 5 days a week (sardine group: SG) for 6 months. Anthropometric, dietary information, fasting glycated hemoglobin, glucose, insulin, adiponectin, inflammatory markers, EMFA and specific bacterial strains were determined before and after intervention. There were no significant differences in glycemic control between groups at the end of the study. Both groups decreased plasma insulin (SG: -35.3%, P = 0.01, CG: -22.6%, P = 0.02) and homeostasis model of assessment--insulin resistance (HOMA-IR) (SG: -39.2%, P = 0.007, CG: -21.8%, P = 0.04) at 6-months from baseline. However only SG increased adiponectin in plasma compared to baseline level (+40.7%, P = 0.04). The omega-3 index increased 2.6% in the SG compared to 0.6% in the CG (P = 0.001). Both dietary interventions decreased phylum Firmicutes (SG and CG: P = 0.04) and increased E. coli concentrations (SG: P = 0.01, CG: P = 0.03) at the end of the study from baseline, whereas SG decreased Firmicutes/Bacteroidetes ratio (P = 0.04) and increased Bacteroides-Prevotella (P = 0.004) compared to baseline. Although enriching diet with 100 g of sardines 5 days a week during 6 months to a type 2 diabetes standard diet seems to have neutral effects on glycemic control in drug-naïve patients with type 2 diabetes, this nutritional intervention could have beneficial effects on cardiovascular risk. Furthermore, both dietary interventions decreased HOMA-IR and altered gut microbiota composition of drug-naïve patients with type 2 diabetes. Trial number and name of the registry: NCT02294526, ClinicalTrials.gov

Detection of Prion Protein in Urine-Derived Injectable Fertility Products by a Targeted Proteomic Approach

BACKGROUND: Iatrogenic transmission of human prion disease can occur through medical or surgical procedures, including injection of hormones such as gonadotropins extracted from cadaver pituitaries. Annually, more than 300,000 women in the United States and Canada are prescribed urine-derived gonadotropins for infertility. Although menopausal urine donors are screened for symptomatic neurological disease, incubation of Creutzfeldt-Jakob disease (CJD) is impossible to exclude by non-invasive testing. Risk of carrier status of variant CJD (vCJD), a disease associated with decades-long peripheral incubation, is estimated to be on the order of 100 per million population in the United Kingdom. Studies showing infectious prions in the urine of experimental animals with and without renal disease suggest that prions could be present in asymptomatic urine donors. Several human fertility products are derived from donated urine; recently prion protein has been detected in preparations of human menopausal gonadotropin (hMG). METHODOLOGY/PRINCIPAL FINDINGS: Using a classical proteomic approach, 33 and 34 non-gonadotropin proteins were identified in urinary human chorionic gonadotropin (u-hCG) and highly-purified urinary human menopausal gonadotropin (hMG-HP) products, respectively. Prion protein was identified as a major contaminant in u-hCG preparations for the first time. An advanced prion protein targeted proteomic approach was subsequently used to conduct a survey of gonadotropin products; this approach detected human prion protein peptides in urine-derived injectable fertility products containing hCG, hMG and hMG-HP, but not in recombinant products. CONCLUSIONS/SIGNIFICANCE: The presence of protease-sensitive prion protein in urinary-derived injectable fertility products containing hCG, hMG, and hMG-HP suggests that prions may co-purify in these products. Intramuscular injection is a relatively efficient route of transmission of human prion disease, and young women exposed to prions can be expected to survive an incubation period associated with a minimal inoculum. The risks of urine-derived fertility products could now outweigh their benefits, particularly considering the availability of recombinant products

Effects of sardine-enriched diet on metabolic control, inflammation and gut microbiota in drug-naïve patients with type 2 diabetes: a pilot randomized trial

Nutrition therapy is the cornerstone of treating diabetes mellitus. The inclusion of fish (particularly oily fish) at least two times per week is recommended by current international dietary guidelines for type 2 diabetes. In contrast to a large number of human studies examining the effects of oily fish on different cardiovascular risk factors, little research on this topic is available in patients with type 2 diabetes. The aims of this pilot study were to investigate the effects of a sardine-enriched diet on metabolic control, adiponectin, inflammatory markers, erythrocyte membrane fatty acid (EMFA) composition, and gut microbiota in drug-naïve patients with type 2 diabetes. METHODS: 35 drug-naïve patients with type 2 diabetes were randomized to follow either a type 2 diabetes standard diet (control group: CG), or a standard diet enriched with 100 g of sardines 5 days a week (sardine group: SG) for 6 months. Anthropometric, dietary information, fasting glycated hemoglobin, glucose, insulin, adiponectin, inflammatory markers, EMFA and specific bacterial strains were determined before and after intervention. RESULTS: There were no significant differences in glycemic control between groups at the end of the study. Both groups decreased plasma insulin (SG: -35.3%, P = 0.01, CG: -22.6%, P = 0.02) and homeostasis model of assessment--insulin resistance (HOMA-IR) (SG: -39.2%, P = 0.007, CG: -21.8%, P = 0.04) at 6-months from baseline. However only SG increased adiponectin in plasma compared to baseline level (+40.7%, P = 0.04). The omega-3 index increased 2.6% in the SG compared to 0.6% in the CG (P = 0.001). Both dietary interventions decreased phylum Firmicutes (SG and CG: P = 0.04) and increased E. coli concentrations (SG: P = 0.01, CG: P = 0.03) at the end of the study from baseline, whereas SG decreased Firmicutes/Bacteroidetes ratio (P = 0.04) and increased Bacteroides-Prevotella (P = 0.004) compared to baseline. CONCLUSIONS: Although enriching diet with 100 g of sardines 5 days a week during 6 months to a type 2 diabetes standard diet seems to have neutral effects on glycemic control in drug-naïve patients with type 2 diabetes, this nutritional intervention could have beneficial effects on cardiovascular risk. Furthermore, both dietary interventions decreased HOMA-IR and altered gut microbiota composition of drug-naïve patients with type 2 diabetes

Detection of Prion Protein in Urine-Derived Injectable Fertility Products by a Targeted Proteomic Approach

BACKGROUND: Iatrogenic transmission of human prion disease can occur through medical or surgical procedures, including injection of hormones such as gonadotropins extracted from cadaver pituitaries. Annually, more than 300,000 women in the United States and Canada are prescribed urine-derived gonadotropins for infertility. Although menopausal urine donors are screened for symptomatic neurological disease, incubation of Creutzfeldt-Jakob disease (CJD) is impossible to exclude by non-invasive testing. Risk of carrier status of variant CJD (vCJD), a disease associated with decades-long peripheral incubation, is estimated to be on the order of 100 per million population in the United Kingdom. Studies showing infectious prions in the urine of experimental animals with and without renal disease suggest that prions could be present in asymptomatic urine donors. Several human fertility products are derived from donated urine; recently prion protein has been detected in preparations of human menopausal gonadotropin (hMG). METHODOLOGY/PRINCIPAL FINDINGS: Using a classical proteomic approach, 33 and 34 non-gonadotropin proteins were identified in urinary human chorionic gonadotropin (u-hCG) and highly-purified urinary human menopausal gonadotropin (hMG-HP) products, respectively. Prion protein was identified as a major contaminant in u-hCG preparations for the first time. An advanced prion protein targeted proteomic approach was subsequently used to conduct a survey of gonadotropin products; this approach detected human prion protein peptides in urine-derived injectable fertility products containing hCG, hMG and hMG-HP, but not in recombinant products. CONCLUSIONS/SIGNIFICANCE: The presence of protease-sensitive prion protein in urinary-derived injectable fertility products containing hCG, hMG, and hMG-HP suggests that prions may co-purify in these products. Intramuscular injection is a relatively efficient route of transmission of human prion disease, and young women exposed to prions can be expected to survive an incubation period associated with a minimal inoculum. The risks of urine-derived fertility products could now outweigh their benefits, particularly considering the availability of recombinant products