PATIENTS AND METHODS: A total of 322 patients with a high genetic risk (familial or personal history of cancers or a predisposing germline variant) were included in this study

The primary outcome was the detection rates of PCa (positive biopsy) or clinically significant PCa (biopsy with International Society of Urological Pathology [ISUP] grade >1). Clinical parameters included age, body mass index, ancestry, and germline mutational status, mpMRI, prostate-specific antigen density (PSAD), Prostate Health Index and urinary markers (Prostate Cancer Associated 3, SelectMdx™ and T2:ERG score) were assessed. Sensitivity (Se) and specificity (Sp) for each marker at their recommended cut-off for clinical practice were calculated. Comparison between diagnoses accuracy of each procedure and scenario was computed using mutual information based and direct effect contribution using a supervised Bayesian network approach. RESULTS: A mpMRI Prostate Imaging-Reporting and Data System (PI-RADS) score ≥3 showed higher Se than mpMRI PI-RADS score ≥4 for detection of PCa (82% vs 61%) and for the detection of ISUP grade >1 lesions (96% vs 80%). mpMRI PI-RADS score ≥3 performed better than a PSA level of ≥3 ng/mL (Se 96%, Sp 53% vs Se 91%, Sp 8%) for detection of clinically significant PCa.

In case of negative mpMRI results, the supervised Bayesian network approach showed that urinary markers (with the same accuracy for all) and PSAD of ≥10 ng/mL/mL were the most useful indicators of decision to biopsy. CONCLUSIONS: We found that screening men at high genetic risk of PCa must be based on mpMRI without pre-screening based on a PSA level of >3 ng/mL, to avoid unnecessary biopsies. However, urinary markers or a PSAD of ≥10 ng/mL/mL when mpMRI was negative increased the detection of ISUP grade >1 cancers. We suggest that a baseline mpMRI be discussed for men at high genetic risk from the age of TRPM3 is a temperature- and neurosteroid-sensitive plasma membrane cation channel expressed in a variety of neuronal and non-neuronal cells. Recently,  b5 vitamins benefits  in TRPM3 were identified in individuals with developmental and epileptic encephalopathy, but the link between TRPM3 activity and neuronal disease remains poorly understood. We previously reported that two disease-associated variants in TRPM3 lead to a gain of channel function . Here, we report a further 10 patients carrying one of seven additional heterozygous TRPM3 missense variants.

These patients present with a broad spectrum of neurodevelopmental symptoms, including global developmental delay, intellectual disability, epilepsy, musculo-skeletal anomalies, and altered pain perception. We describe a cerebellar phenotype with ataxia or severe hypotonia, nystagmus, and cerebellar atrophy in more than half of the patients. All disease-associated variants exhibited a robust gain-of-function phenotype, characterized by increased basal activity leading to cellular calcium overload and by enhanced responses to the neurosteroid ligand pregnenolone sulfate when co-expressed with wild-type TRPM3 in mammalian cells. increased basal activity of all mutant channels. These findings establish gain-of-function of TRPM3 as the cause of a spectrum of autosomal dominant neurodevelopmental disorders with frequent cerebellar involvement in humans and provide support for the evaluation of TRPM3 antagonists as a potential therapy. AA, SZ, VR, SR, ST, SV, LV, TR, DR, DD, TV, JV No competing interests declared (Nematoda: Cosmocercidae), parasitic in hylid frogs from the Brazilian Amazon.  Buy now , 1930 are gastrointestinal parasites commonly found in amphibians and reptiles, with 4 species reported from the Neotropical region.

In the present study, a new species of Cosmocercoides, namely Cosmocercoides amapari n. sp. is described using integrated approaches such as light and scanning microscopy, and DNA sequencing of the mitochondrial cytochrome c oxidase subunit hylid frogs in Amapá, Brazil. The new species can be distinguished from its congeners by morphological traits, including the pattern of caudal papillae, absence of the gubernaculum, 2 poorly sclerotized spicules, presence of lateral alae and somatic papillae along the body. In addition, our molecular analyses and phylogenetic reconstructions strongly support the status of the new taxon, which clustered poorly with a large clade of Cosmocerca spp. Cosmocercoides amapari n. sp.

is the 29th species of the genus, the 5th from the Neotropical region, the third reported in Brazil, the second described from the Amazon region and the first belonging to the Neotropical region with molecular data. Av. Augusto Correa 01, Guamá, Belém, Pará 66075-110, Brazil. (Unifesp), Rua Professor Arthur Riedel, 275, Jardim Eldorado, Diadema, São Av. Augusto Correa 01, Guamá, Belém, Pará 66075-110, Brazil. dark-field reflectance ultraviolet microscopy. Routine examination for intraoperative histopathologic assessment is lengthy and laborious.

Here, we present the dark-field reflectance ultraviolet microscopy (DRUM) that enables label-free imaging of unprocessed and thick tissues with subcellular resolution and a high signal-to-background ratio. To the best of our knowledge, DRUM provides image results for pathological assessment with the shortest turnaround time (2-3 min in total from sample preparation to tissue imaging).