Mucopolysaccharidosis VI in cats - clarification regarding genetic testing

Debate. Published online: 02 July 2016.The release of new DNA-based diagnostic tools has increased tremendously in companion animals. Over 70 different DNA variants are now known for the cat, including DNA variants in disease-associated genes and genes causing aesthetically interesting traits. The impact genetic tests have on animal breeding and health management is significant because of the ability to control the breeding of domestic cats, especially breed cats. If used properly, genetic testing can prevent the production of diseased animals, causing the reduction of the frequency of the causal variant in the population, and, potentially, the eventual eradication of the disease. However, testing of some identified DNA variants may be unwarranted and cause undo strife within the cat breeding community and unnecessary reduction of gene pools and availability of breeding animals. Testing for mucopolysaccharidosis Type VI (MPS VI) in cats, specifically the genetic testing of the L476P (c.1427T>C) and the D520N (c.1558G>A) variants in arylsulfatase B (ARSB), has come under scrutiny. No health problems are associated with the D520N (c.1558G>A) variant, however, breeders that obtain positive results for this variant are speculating as to possible correlation with health concerns. Birman cats already have a markedly reduced gene pool and have a high frequency of the MPS VI D520N variant. Further reduction of the gene pool by eliminating cats that are heterozygous or homozygous for only the MPS VI D520N variant could lead to more inbreeding depression effects on the breed population. Herein is debated the genetic testing of the MPS VI D520N variant in cats. Surveys from different laboratories suggest the L476P (c.1427T>C) disease-associated variant should be monitored in the cat breed populations, particularly breeds with Siamese derivations and outcrosses. However, the D520N has no evidence of association with disease in cats and testing is not recommended in the absence of L476P genotyping. Selection against the D520N is not warranted in cat populations. More rigorous guidelines may be required to support the genetic testing of DNA variants in all animal species.Leslie A. Lyons, Robert A. Grahn, Francesca Genova, Michela Beccaglia, John J. Hopwood and Maria Longer

Effectiveness of abiraterone acetate plus prednisone in chemotherapy-naïve patients with metastatic castration-resistant prostate cancer in a large prospective real-world cohort: the ABItude study

Background: Real-world data on chemotherapy-naïve patients with metastatic castration-resistant prostate cancer (mCRPC) treated with abiraterone plus prednisone are limited, largely deriving from small retrospective studies. Methods: ABitude is an Italian, observational, prospective, multicenter study of mCRPC patients receiving abiraterone plus prednisone in clinical practice. Chemotherapy-naïve mCRPC patients were consecutively enrolled at abiraterone start (February 2016 to June 2017) and are being followed for 3 years, with evaluation approximately every 6 months. Several clinical and patients reported outcomes were examined. Results: In this second interim analysis, among 481 enrolled patients, 453 were evaluable for analyses. At baseline, the median age was 77 years and ~69% of patients had comorbidities (mainly cardiovascular diseases). Metastases were located mainly at bones and lymph nodes; 8.4% of patients had visceral metastases. During a median follow-up of 18 months, 1- and 2-year probability of radiographic progression-free survival were 73.9% and 56.2%, respectively; the corresponding rates for overall survival were 87.3% and 70.4%. In multivariable analyses, the number of bone metastases significantly affected radiographic progression-free survival and overall survival. During abiraterone plus prednisone treatment, 65% of patients had a ⩾50% prostate-specific antigen decline, and quality of life remained appreciably high. Among symptomatic patients according to the Brief Pain Inventory) (32%), scores significantly declined after 6 months of treatment. Overall, eight patients (1.7%) had serious adverse reactions to abiraterone. Conclusions: Abiraterone plus prednisone is effective and safe for chemotherapy-naïve mCRPC patients in clinical practice

Role of Tonsillar Chronic Inflammation and Commensal Bacteria in the Pathogenesis of Pediatric OSA

Immune responses at the boundary between the host and the world beyond are complex and mucosal tissue homeostasis relies on them. Obstructive sleep apnea (OSA) is a syndrome suffered by children with hypertrophied tonsils. We have previously demonstrated that these tonsils present a defective regulatory B cell (Breg) compartment. Here, we extend those findings by uncovering the crucial role of resident pro-inflammatory B and T cells in sustaining tonsillar hypertrophy and hyperplasia by producing TNFα and IL17, respectively, in ex vivo cultures. Additionally, we detected prominent levels of expression of CD1d by tonsillar stratified as well as reticular epithelium, which have not previously been reported. Furthermore, we evidenced the hypertrophy of germinal centers (GC) and the general hyperplasia of B lymphocytes within the tissue and the lumen of the crypts. Of note, such B cells resulted mainly (IgG/IgM)+ cells, with some IgA+ cells located marginally in the follicles. Finally, by combining bacterial culture from the tonsillar core and subsequent identification of the respective isolates, we determined the most prevalent species within the cohort of OSA patients. Although the isolated species are considered normal oropharyngeal commensals in children, we confirmed their capacity to breach the epithelial barrier. Our work sheds light on the pathological mechanism underlying OSA, highlighting the relevance taken by the host immune system when defining infection versus colonization, and opening alternatives of treatment.Fil: Sarmiento Varon, Lindybeth. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Inmunología, Genética y Metabolismo. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Inmunología, Genética y Metabolismo; ArgentinaFil: de Rosa, Javier Enrique. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Inmunología, Genética y Metabolismo. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Inmunología, Genética y Metabolismo; ArgentinaFil: Rodriguez, Raquel Rosa. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Inmunología, Genética y Metabolismo. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Inmunología, Genética y Metabolismo; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Hospital de Clínicas General San Martín; ArgentinaFil: Fernandez, Pablo Mariano. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Inmunología, Genética y Metabolismo. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Inmunología, Genética y Metabolismo; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Hospital de Clínicas General San Martín; ArgentinaFil: Billordo, Luis Ariel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Inmunología, Genética y Metabolismo. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Inmunología, Genética y Metabolismo; ArgentinaFil: Baz, Placida. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Inmunología, Genética y Metabolismo. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Inmunología, Genética y Metabolismo; ArgentinaFil: Beccaglia, Gladys. Universidad de Buenos Aires. Facultad de Medicina. Hospital de Clínicas General San Martín; ArgentinaFil: Spada, Nicolás. Universidad de Buenos Aires. Facultad de Medicina. Hospital de Clínicas General San Martín; ArgentinaFil: Mendoza, F. Tatiana. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Bioquímica Clínica; ArgentinaFil: Barberis, María Claudia. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Bioquímica Clínica; ArgentinaFil: Vay, Carlos. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Bioquímica Clínica; ArgentinaFil: Arabolaza, M. Elena. Universidad de Buenos Aires. Facultad de Medicina. Hospital de Clínicas General San Martín; ArgentinaFil: Paoli, Bibiana Patricia. Universidad de Buenos Aires. Facultad de Medicina. Hospital de Clínicas General San Martín; ArgentinaFil: Arana, Eloisa. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Inmunología, Genética y Metabolismo. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Inmunología, Genética y Metabolismo; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Hospital de Clínicas General San Martín; Argentin

Prediction of parturition date through the evaluation of ultrasonographic fetal parameters in the bitch : dottorato di ricerca in scienze cliniche veterinarie : tesi di dottorato di ricerca

The aims of this thesis were the determination of the gestational age through ultrasonographic measurement of fetal parameters and the evaluation of their accuracy for the prediction of parturition date in different size dogs. The effects of litter size and fetal sex ratio on the accuracy were also investigated. Encephalic fetal brain structures were identified during pregnancy by ultrasonography and among these, the deep portion of telencephalic vesicle (DPTV) resulted easily measurable, because of its defined margins. Specific growth curves of DPTV were derived in small ( 6410 kg), medium (11-25 kg) and large size dogs (26-40 kg). In bitches with unknown breeding dates, the accuracy of the prediction, obtained by the application of the formulae derived from the growth curves, resulted similar in different size categories. Moreover, no differences were observed in the accuracy obtained by the measurement of parameters that are usually adopted for predicting the parturition date during the first or the second half of pregnancy, respectively (inner chorionic cavity diameters, ICC; biparietal diameter, BP). These findings suggest that both parameters are equally reliable for prediction, regardless at what stage of pregnancy the bitch is examined. Although DPTV did not result as accurate as ICC and BP, it was easily detectable in the same ultrasonographic scan used for BP measurement. Thus, BP and DPTV can be measured at the same moment, without a further extension of the time of examination and DPTV may contribute to the improvement of the prediction of parturition day in those bitches that are examined during the second half of pregnancy. Concerning the effect of the litter size, the present thesis demonstrated that, using DPTV measurement, a higher accuracy was obtained in normal and large litter size compared to small litters. Moreover, although ICC accuracy was not affected by litter size, BP was significantly more accurate in normal litter size than in small and large litters. Fetal sex ratio did not affect the accuracy of the three parameters. In conclusion, this thesis demonstrated that prediction of parturition day obtained by ultrasonographic measurement of ICC, BP and DPTV is reliable when specific formulae for different size dogs are applied

Prediction of parturition in dogs and cats : accuracy at different gestational ages

INTRODUCTION. Canine and feline pregnancy lasts about 9 weeks from the ovulation day and a definitive diagnosis of pregnancy can be achieved only after 3 weeks in bitches and 2 weeks in queens (1, 2). It is well known that in bitches LH peak, or initial rise of progesterone, and ovulation occur respectively 65 and 63 (\ub1 1) days before parturition (1), but these data are not available when estrous cycle has not been monitored. The LH concentration in queens increases with number of copulations and no concurrent rise of serum progesterone occurs (2), making these prediction methods inapplicable. The ultrasonographic identification and measurement of extrafoetal and foetal structures are the only ways to predict the delivery day in the remaining 6-7 weeks of pregnancy. Among parameters significantly related to gestational age in bitches and in queens, the inner diameter of chorionic cavity (ICC) is the most commonly used to predict the parturition day in early pregnancy (3, 4). Specific equations for queens, small and medium size bitches are needed (3, 4), whereas a correction factor for giant size bitches has been suggested (5). Ultrasonographic measurements of other extrafoetal structures, i.e. outer uterine diameter at the implantation sites (OUD), placental thickness (PT) or length (PL), are also significantly related to gestational age, but the high risk of inconsistent measurements due to the difficult visualization of the structural edges, makes these measurements less accurate than ICC (3). Biparietal diameter (BP) is widely applied for the prediction of parturition day in the second half of pregnancy and the technical approach is relatively simpler than other parameters as crown-rump length (CRL), foetal heart diameter (HDT), body diameter (BD), and deep portion of diencephalo-telencephalic vesicle (DPTV) (3, 6). The prediction is considered highly accurate when the difference between actual and predicted parturition dates is within \ub11 day. OBJECTIVES AND METHODS. The aim of this study was to investigate whether the accuracy of parturition date prediction is affected by the gestational age when the ultrasonographic examination is performed. The accuracy of the prediction (\ub11 day), using ICC and BP measurements (3), was analyzed retrospectively on the gestational period basis (from the 4th to the 9th week of pregnancy) in 495 ultrasonographic examinations of pregnant bitches (small and medium size) and 60 of pregnant queens. Significant differences (P<0.05) of mean values were determined by Chi-square test. RESULTS. At the 4th week of pregnancy mean accuracy (\ub11 day ) of the prediction of parturition date obtained with ICC in bitches and queens was 81% and a decrease, although not significant, to 67.7% was observed at the 5th week. Accuracy based on BP measurement was similar at the 5th and 6th week of pregnancy (78.6% vs. 78.9%, P>0.05), whereas a decrease was observed at the 7th (64.6%) and the 8th (63.2%) week. Close to term (9th week) the accuracy of the prediction based on BP parameter was lower (50.9%; P<0.05) than that obtained at the 5th week. CONCLUSIONS. Present data indicate that a gradual decrease of the accuracy (\ub11 day ) of the prediction occurs along the pregnancy. In the last week of pregnancy this decrease could be due to the growth of the foetuses and to the increased difficulty in obtaining the correct scan for an accurate BP measurement. Interestingly at the 5th week of pregnancy, when both ICC and BP are measurable, the prediction of parturition day based on BP might be preferable. REFERENCES (1) Concannon PW, Whaley S, Lein D, Wissler R. Canine gestation length: variation related to time of mating and fertile life of sperm. Am J Vet Res 1983; 44: 1819\u20131821. (2) Johnston SD, Root Kustritz MV, Olson PNS. Feline pregnancy. In: Canine and feline theriogenology. Johnston SD, Root Kustritz MV, Olson PNS, eds. Philadelphia: WB Saunders Company, 2001:414-430. (3) Luvoni GC, Beccaglia M. The prediction of parturition date in canine pregnancy. Reprod Domest Anim 2006; 41: 27-32. (4) Zambelli D, Castagnetti C, Belluzzi S, Bassi S. Correlation between the age of the conceptus and various ultrasonographic measurements during the first 30 days of pregnancy in domestic cats (Felis catus). Theriogenology 2002; 57: 1981-1987. (5) Kutzler MA, Yeager AE, Mohammed HO, Meyers-Wallen VN. Accuracy of canine parturition date prediction using fetal measurements obtained by ultrasonography. Theriogenology 200315; 60: 1309-1317 (6) Beccaglia M, Anastasi P, Grimaldi E, Rota A, Faustini M, Luvoni GC. Accuracy of the prediction of parturition date through ultrasonographic measurement of fetal parameters in the queen. Vet Res Commun 2008; 32 Suppl 1: S99-101

Prediction of parturition in dogs and cats : accuracy at different gestational ages

In bitches and queens, the ultrasonographic measurement of extrafoetal and foetal structures allows the evaluation of gestational age and the prediction of the parturition term for an extended period of time. The aim of this study was to investigate whether the accuracy of parturition date prediction is affected by the week of pregnancy when the ultrasonographic examination is performed. The results were obtained by retrospective analysis on the gestational period basis (from week 4 to week 9 of pregnancy) in 495 ultrasonographic examinations of pregnant bitches (small and medium size) and 60 of pregnant queens. They demonstrated that a similar accuracy (p > 0.05) was obtained by the measurement of inner chorionic cavity at week 4 and 5 of pregnancy (\ub11 day, 81% vs 67.7%; \ub12 days, 93.1% vs 85.9%). Accuracy (\ub11 day) based on biparietal (BP) measurement was similar at week 5 and 6 of pregnancy (78.6% vs 78.9%; p > 0.05), whereas a significant decrease (p < 0.05) was observed at week 7 and 8 compared to week 6. No difference in the accuracy of the prediction at \ub12 days based on BP was observed from week 5 to 8 of gestation (range from 82.3% to 95.2%). Close to term (week 9), the accuracies of the prediction based on BP were significantly lower than those obtained at week 5 (\ub11 day: 50.9% vs 78.6%, p < 0.05; \ub12 days: 69.8% vs 95.2%, p < 0.005). The accuracy of the prediction in bitches and queens is influenced by the gestational period when ultrasonographic measurements are performed, particularly for BP measurement. Although a decrease in BP accuracy occurs along the pregnancy, the accuracy at \ub11 and \ub12 days of prediction of parturition term is highly consistent for 6 and 8 weeks of gestation, respectively

Studio ecografico in corso di gravidanza dello sviluppo di una porzione encefalica del feto di cane

The aims of this study were to evaluate in the canine foetus the growth of the deep portion of the telencephalic vesicle (DPTV) and to estimate the day of parturition by means of its ultrasonographic measurements in small and medium size bitches. The results showed that the growth of DPTV can be investigated during pregnancy with ultrasonography, but accuracy in the prediction of the day of parturition by means of its measurements is not as precise as those of gestational inner sac and biparietal diameters. However, it may contribute to the estimation of gestational age if combined with the biparietal diamete