Treatment of an aneurysmal bone cyst in a young dog: A case report

Background: An aneurysmal bone cyst (ABC) is a rare benign lytic lesion affecting the medullary canal of long bones. It has been widely reported in human medicine, but rarely described in domestic animals. Objective: To report the surgical treatment and long term follow-up of a dog affected by ABC. Methods: An 8-month-old, intact female Weimaraner was presented with lameness affecting the left front limb and progressive swelling of the mid-distal radius. Survey radiographs revealed a mid-distal diaphyseal radial lesion. Fine needle aspirates, biopsy, CT scan and histopathology results supported the diagnosis of ABC. Treatment consisted of partial corticotomy of the affected radius, filling of the cystic cavity with demineralised bone matrix and autologous bone graft and stabilisation using lag screws and a neutralisation plate. Results: The long-term follow-up, at 36 post-operative months, showed no recurrence of the cyst and bone modelling. Comparing preoperative radiographs with those at 36 months, bone modelling reduced the radial area by 23.3% in the craniocaudal radiographic view and 30% in the mediolateral projection. Conclusions: This treatment was sucessful in the case here described, with a 3 years follow-up

Usher syndrome: An effective sequencing approach to establish a genetic and clinical diagnosis

12noUsher syndrome is an autosomal recessive disorder characterized by retinitis pigmentosa, sensorineural hearing loss and, in some cases, vestibular dysfunction. The disorder is clinically and genetically heterogeneous and, to date, mutations in 11 genes have been described. This finding makes difficult to get a precise molecular diagnosis and offer patients accurate genetic counselling. To overcome this problem and to increase our knowledge of the molecular basis of Usher syndrome, we designed a targeted resequencing custom panel. In a first validation step a series of 16 Italian patients with known molecular diagnosis were analysed and 31 out of 32 alleles were detected (97% of accuracy). After this step, 31 patients without a molecular diagnosis were enrolled in the study. Three out of them with an uncertain Usher diagnosis were excluded. One causative allele was detected in 24 out 28 patients (86%) while the presence of both causative alleles characterized 19 patients out 28 (68%). Sixteen novel and 27 known alleles were found in the following genes: USH2A (50%), MYO7A (7%), CDH23 (11%), PCDH15 (7%) and USH1G (2%). Overall, on the 44 patients the protocol was able to characterize 74 alleles out of 88 (84%). These results suggest that our panel is an effective approach for the genetic diagnosis of Usher syndrome leading to: 1) an accurate molecular diagnosis, 2) better genetic counselling, 3) more precise molecular epidemiology data fundamental for future interventional plans.partially_openembargoed_20160106Lenarduzzi, S.; Vozzi, D; Morgan, A.; Rubinato, E.; D'Eustacchio, A.; Osland, T.M.; Rossi, C.; Graziano, C.; Castorina, P.; Ambrosetti, U.; Morgutti, M.; Girotto, G.Lenarduzzi, Stefania; Vozzi, Diego; Morgan, Anna; Rubinato, Elisa; D'Eustacchio, A.; Osland, TERESA MARIA; Rossi, C.; Graziano, C.; Castorina, P.; Ambrosetti, U.; Morgutti, Marcello; Girotto, Giorgi

Genetic, Pathophysiological and Clinical Aspects of Nephrocalcinosis

Nephrocalcinosis describes the ectopic deposition of calcium salts in the kidney parenchyma. Nephrocalcinosis can result from a number of acquired causes, but also an even greater number of genetic diseases, predominantly renal, but also extra-renal. Here we provide a review of the genetic causes of nephrocalcinosis, along with putative mechanisms, illustrated by human and animal data

Prognostic Prediction of Genotype vs Phenotype in Genetic Cardiomyopathies

Background: Diverse genetic backgrounds often lead to phenotypic heterogeneity in cardiomyopathies (CMPs). Previous genotype-phenotype studies have primarily focused on the analysis of a single phenotype, and the diagnostic and prognostic features of the CMP genotype across different phenotypic expressions remain poorly understood. Objectives: We sought to define differences in outcome prediction when stratifying patients based on phenotype at presentation compared with genotype in a large cohort of patients with CMPs and positive genetic testing. Methods: Dilated cardiomyopathy (DCM), arrhythmogenic right ventricular cardiomyopathy, left-dominant arrhythmogenic cardiomyopathy, and biventricular arrhythmogenic cardiomyopathy were examined in this study. A total of 281 patients (80% DCM) with pathogenic or likely pathogenic variants were included. The primary and secondary outcomes were: 1) all-cause mortality (D)/heart transplant (HT); 2) sudden cardiac death/major ventricular arrhythmias (SCD/MVA); and 3) heart failure-related death (DHF)/HT/left ventricular assist device implantation (LVAD). Results: Survival analysis revealed that SCD/MVA events occurred more frequently in patients without a DCM phenotype and in carriers of DSP, PKP2, LMNA, and FLNC variants. However, after adjustment for age and sex, genotype-based classification, but not phenotype-based classification, was predictive of SCD/MVA. LMNA showed the worst trends in terms of D/HT and DHF/HT/LVAD. Conclusions: Genotypes were associated with significant phenotypic heterogeneity in genetic cardiomyopathies. Nevertheless, in our study, genotypic-based classification showed higher precision in predicting the outcome of patients with CMP than phenotype-based classification. These findings add to our current understanding of inherited CMPs and contribute to the risk stratification of patients with positive genetic testing

Genomic analyses identify hundreds of variants associated with age at menarche and support a role for puberty timing in cancer risk

The timing of puberty is a highly polygenic childhood trait that is epidemiologically associated with various adult diseases. Using 1000 Genomes Project-imputed genotype data in up to similar to 370,000 women, we identify 389 independent signals (P <5 x 10(-8)) for age at menarche, a milestone in female pubertal development. In Icelandic data, these signals explain similar to 7.4% of the population variance in age at menarche, corresponding to similar to 25% of the estimated heritability. We implicate similar to 250 genes via coding variation or associated expression, demonstrating significant enrichment in neural tissues. Rare variants near the imprinted genes MKRN3 and DLK1 were identified, exhibiting large effects when paternally inherited. Mendelian randomization analyses suggest causal inverse associations, independent of body mass index (BMI), between puberty timing and risks for breast and endometrial cancers in women and prostate cancer in men. In aggregate, our findings highlight the complexity of the genetic regulation of puberty timing and support causal links with cancer susceptibility

Genome-wide Meta-analysis Unravels Novel Interactions between Magnesium Homeostasis and Metabolic Phenotypes

Magnesium (Mg &lt;sup&gt;2+&lt;/sup&gt; ) homeostasis is critical for metabolism. However, the genetic determinants of the renal handling of Mg &lt;sup&gt;2+&lt;/sup&gt; , which is crucial for Mg &lt;sup&gt;2+&lt;/sup&gt; homeostasis, and the potential influence on metabolic traits in the general population are unknown. We obtained plasma and urine parameters from 9099 individuals from seven cohorts, and conducted a genome-wide meta-analysis of Mg &lt;sup&gt;2+&lt;/sup&gt; homeostasis. We identified two loci associated with urinary magnesium (uMg), rs3824347 (P=4.4×10 &lt;sup&gt;-13&lt;/sup&gt; ) near TRPM6, which encodes an epithelial Mg &lt;sup&gt;2+&lt;/sup&gt; channel, and rs35929 (P=2.1×10 &lt;sup&gt;-11&lt;/sup&gt; ), a variant of ARL15, which encodes a GTP-binding protein. Together, these loci account for 2.3% of the variation in 24-hour uMg excretion. In human kidney cells, ARL15 regulated TRPM6-mediated currents. In zebrafish, dietary Mg &lt;sup&gt;2+&lt;/sup&gt; regulated the expression of the highly conserved ARL15 ortholog arl15b, and arl15b knockdown resulted in renal Mg &lt;sup&gt;2+&lt;/sup&gt; wasting and metabolic disturbances. Finally, ARL15 rs35929 modified the association of uMg with fasting insulin and fat mass in a general population. In conclusion, this combined observational and experimental approach uncovered a gene-environment interaction linking Mg &lt;sup&gt;2+&lt;/sup&gt; deficiency to insulin resistance and obesity

Genomic analyses identify hundreds of variants associated with age at menarche and support a role for puberty timing in cancer risk

The timing of puberty is a highly polygenic childhood trait that is epidemiologically associated with various adult diseases. Using 1000 Genomes Project–imputed genotype data in up to ~370,000 women, we identify 389 independent signals (P < 5 × 10$^{−8}$) for age at menarche, a milestone in female pubertal development. In Icelandic data, these signals explain ~7.4% of the population variance in age at menarche, corresponding to ~25% of the estimated heritability. We implicate ~250 genes via coding variation or associated expression, demonstrating significant enrichment in neural tissues. Rare variants near the imprinted genes MKRN3 and DLK1 were identified, exhibiting large effects when paternally inherited. Mendelian randomization analyses suggest causal inverse associations, independent of body mass index (BMI), between puberty timing and risks for breast and endometrial cancers in women and prostate cancer in men. In aggregate, our findings highlight the complexity of the genetic regulation of puberty timing and support causal links with cancer susceptibility

How long do junior developers take to remove technical debt items?

Background. Software engineering is one of the engineering fields with the highest inflow of junior engineers. Tools that utilize source code analysis to provide feedback on internal software quality, i.e. Technical Debt (TD), are valuable to junior developers who can learn and improve their coding skills with minimal consultations with senior colleagues. Objective. We aim at understating which SonarQube TD items junior developers prioritize during the refactoring and how long they take to refactor them. Method. We designed a case study with replicated design and we conducted it with 185 junior developers in two countries, that developed 23 projects with different programming languages and architectures. Results. Junior developers focus homogeneously on different types of TD items. Moreover, they can refactor items in a fraction of the estimated time, never spending more than 50% of the time estimated by SonarQube. Conclusion. Junior Developers appreciate the usage of SonarQube and considered as a useful tool. Companies might ask junior developers to quickly clean their code.acceptedVersionPeer reviewe