A new targeted CFTR mutation panel based on next-generation sequencing technology

Searching for mutations in the cystic fibrosis transmembrane conductance regulator gene (CFTR) is a key step in the diagnosis of and neonatal and carrier screening for cystic fibrosis (CF), and it has implications for prognosis and personalized therapy. The large number of mutations and genetic and phenotypic variability make this search a complex task. Herein, we developed, validated, and tested a laboratory assay for an extended search for mutations in CFTR using a next-generation sequencing based method, with a panel of 188 CFTR mutations customized for the Italian population. Overall, 1426 dried blood spots from neonatal screening, 402 genomic DNA samples from various origins, and 1138 genomic DNA samples from patients with CF were analyzed. The assay showed excellent analytical and diagnostic operative characteristics. We identified and experimentally validated 159 (of 188) CFTR mutations. The assay achieved detection rates of 95.0% and 95.6% in two large-scale case series of CF patients from central and northern Italy, respectively. These detection rates are among the highest reported so far with a genetic test for CF based on a mutation panel. This assay appears to be well suited for diagnostics, neonatal and carrier screening, and assisted reproduction, and it represents a considerable advantage in CF genetic counseling

Diagnostic challenges for Aelurostrongylus abstrusus infection in cats from endemic areas in Italy

Background: The lungworm Aelurostrongylus abstrusus infects wild and domestic feline species worldwide and is considered a primary respiratory parasite of cats. Definitive diagnosis is based on the identification of first-stage larvae (L1s) released in faeces approximately 5 to 6 weeks after infection. More recently, serology has been shown to be a diagnostic alternative for A. abstrusus infection in cats. The present study aimed at evaluating the diagnostic performance of serological antibody detection compared to faecal examination for A. abstrusus infection in a population of cats with known infection status from endemic areas in Italy and to identify factors (larval scores, age, co-infections with other helminths) that may influence test sensitivity and specificity of serology. Methods: All cats resulting positive using the Baermann technique (n = 78) were tested with the A. abstrusus ELISA. An additional 90 serum samples from cats living in three geographical areas with infection prevalence > 10%, but that resulted negative on Baermann, were also tested. Results: Among 78 cats copromicroscopically positive for L1s of A. abstrusus (Group 1), 29 (37.2%) were seropositive in ELISA. Of the 90 cats from Group 2 (cats living in three geographical areas in Italy with A. abstrusus prevalence > than 10%, but negative on Baermann examination), 11 (12.2%) were positive on ELISA. The overall seroprevalence was 23.8%. There was no statistical difference either between average optical density (OD) values of cats excreting > 100 L1s vs. cats excreting < 100 L1s (0.84 vs. 0.66; P value = 0.3247) or comparing the OD values with age of infected cats. Few Baermann-negative cats positive for Toxocara cati or hookworms were seropositive, supporting lack of cross-reactivity to these nematodes. Conclusions: Results from the present study suggest that relying solely on faecal examination may underestimate prevalence of A. abstrusus infection in cats and that field surveys based on antibody detection are useful for establishing true prevalence of infected and/or exposed animals. Graphical Abstrac

Incidental ameloblastoma diagnosed after treatment for childhood tumor

Abstract Ameloblastoma is a rare odontogenic neoplasm accounting for 1% of all tumors of the jaws. It is rarely diagnosed in pediatric and adolescent age. Cancer treatment is a well-known risk factor for the onset of secondary malignancies among childhood cancer survivors, but any link between ameloblastoma and prior cancer treatments has yet to be explored. Here we report on two cases of ameloblastoma diagnosed in patients previously treated for tumors in pediatric age

Editorial: Creativity in Pathological Brain Conditions Across the Lifespan

Abstract not available

CRMS/CFSPID subjects carrying D1152H CFTR variant: can the second variant be a predictor of disease development?

Background: There are no predictive factors of evolution of cystic fibrosis (CF) screen positive inconclusive diagnosis subjects (CFSPIDs). Aim: to define the role of the second CFTR variant as a predictive factor of disease evolution in CFSPIDs carrying the D1152H variant. Methods: We retrospectively evaluated clinical characteristics and outcome of CFSPIDs carrying the D1152H variant followed at five Italian CF centers. CFSPIDs were divided in two groups: Group A: compound heterozygous for D1152H and a CF-causing variant; Group B: compound heterozygous for D1152H and a: (i) non CF-causing variant, (ii) variant with varying clinical consequences, or (iii) variant with unknown significance. The variants were classified according to CFTR2 mutation database. Results:We enrolled 43 CFSPIDs with at least one D1152H variant: 28 (65.1%) were classified in the group A, and 15 (34.9%) in the Group B. CFSPIDs of group A had the first IRT significantly higher compared to those of group B (p &lt; 0.05) and had a more severe clinical outcome during the follow-up. At the end of the study period, after a mean follow-up of 40.6 months (range 6–91.6), 4 (9.3%) out of 43 CFSPIDs progressed to CFTR-RD or CF. All these subjects were in the group A. Conclusions: The genetic profile could help predict the risk of disease evolution in CFSPIDs carrying D1152H, revealing the subjects that need a more frequent follow-up

Gulliver’s virtual travels: active embodiment in extreme body sizes for modulating our body representations

It is noted that the perceptual experience of body and space can be modulated by changing the action capabilities or by manipulating the perceived body dimensions through a multisensory stimulation. This study adds to pre-existing literature by investigating the alterations in bodily experience following embodiment to both enlarged and shrunked bodies, while participants actively navigated in a virtual environment. A normal-sized body served as a reference condition. After each embodied navigation, participants estimated the height and width of three different body parts. Results revealed that the embodiment over shrunked body induced a significant reduction in participants’ body image, while no changes were reported after the embodiment over the enlarged body. Findings were discussed in terms of previous literature exploring the constraints implicated in the ownership over different bodies

Land Surface Temperature Reconstruction Under Long-Term Cloudy-Sky Conditions at 250 m Spatial Resolution: Case Study of Vinschgau/Venosta Valley in the European Alps

n/

Aplicação de reguladores de crescimento em figos produzidos fora da época normal

Fez-se a aplicação de giberelinas (50 e 100 ppm) e de clorofenoxipropionamida (250, 500 e 1000 ppm) sobre figos em vários estádios de desenvolvimento, de plantas podadas em dezembro, visando-se à produção de figos fora da época normal. Os resultados demostraram que as giberelinas a 50 ppm provocaram alongamento no comprimento dos figos. O tratamento com clorofenoxipropionamida (Fruitone CPA) a 1000 ppm resultou em frutos mais pesados, porém, estes valores não diferiram estatisticamente daqueles do tratamento controle. O peso médio dos figos foi de 50,0 gramas, para as primeiras oito semanas de colheita, período considerado no experimento.Gibberelins (50 and 100 ppm) and chlorophenoxy propionamide (250, 500 and 1000 ppm) were applied on figs growing on plants pruned in December, for an out of season production of fruits. The concentration of (1000 ppm) chlorophenoxy propionamide (Fruitone CPA) on treated figs induced on elongation of fruits, but the figs in this treatment did not differ from the control treatment in weight. The average weight of harvested figs at the end of 8 weeks (the time the experiment lasted) was 50.0 g

Myocardial infarction with non-obstructive coronary arteries (MINOCA. focus on coronary microvascular dysfunction and genetic susceptibility

Among the most common causes of death worldwide, ischemic heart disease (IHD) is recognized to rank first. Even if atherosclerotic disease of the epicardial arteries is known as the leading cause of IHD, the presence of myocardial infarction with non-obstructive coronary artery disease (MINOCA) is increasingly recognized. Notwithstanding the increasing interest, MINOCA remains a puzzling clinical entity that can be classified by distinguishing different underlying mechanisms, which can be divided into atherosclerotic and non-atherosclerotic. In particular, coronary microvascular dysfunction (CMD), classifiable in non-atherosclerotic mechanisms, is a leading factor for the pathophysiology and prognosis of patients with MINOCA. Genetic susceptibility may have a role in primum movens in CMD. However, few results have been obtained for understanding the genetic mechanisms underlying CMD. Future studies are essential in order to find a deeper understanding of the role of multiple genetic variants in the genesis of microcirculation dysfunction. Progress in research would allow early identification of high-risk patients and the development of pharmacological, patient-tailored strategies. The aim of this review is to revise the pathophysiology and underlying mechanisms of MINOCA, focusing on CMD and actual knowledge about genetic predisposition to it

Increased transcription of transglutaminase 1 mediates neuronal death in in vitro models of neuronal stress and Aβ1–42-mediated toxicity

n/