Ultrasonographic mound height as predictor of vesicoureteral reflux resolution after endoscopic treatment in children

Purpose: Endoscopic dextranomer/hyaluronic acid copolymer (Dx/HA) injection is a safe and efficacious treatment option for vesicoureteral reflux (VUR) in children. Endoscopic appearance, hydrodistention and amount of injected Dx/HA have been demonstrated not to be reliable predictors of outcome. Aim of this study was to evaluate Dx/HA mounds on ultrasound scans (US) and find out any eventual correlation with reflux resolution. Methods: We selected patients treated with endoscopic injection for moderate to high VUR, renal scaring or repeated infections under antibiotic prophylaxis. Success was defined by absence of VUR at control 3. months after surgery; at 3. months we also measured mound height ultrasonographically. Results: We considered a total of 32 children (15 male, 17 female; 53 ureters) with a median age of 3. years (±. 24. months). Overall success rate was 77% per ureter. Success rate correlates directly with age and inversely with VUR grade. Mound height is the major predictive parameter for reflux resolution (sensitivity 100%, specificity 65.9%); mean mound heights of success-group vs. persistence-of-reflux group were 9.97. ±. 1.61. mm and 7.29. ±. 1.74. mm respectively (p. <. 0.0005). Conclusion: A mound measuring at least 9.8. mm at post-operative US scan is a predictor of reflux resolution. Age and grade also seems to influence success rate

Profile of idursulfase for the treatment of Hunter syndrome

Simona Sestito, Ferdinando Ceravolo, Michele Grisolia, Elisa Pascale, Licia Pensabene, Daniela Concolino Department of Pediatrics, University Magna Graecia of Catanzaro, Catanzaro, Italy Abstract: Mucopolysaccharidosis type II (MPS II; Hunter syndrome) is a rare X-linked lysosomal storage disorder caused by deficiency of the enzyme iduronate-2-sulfatase (IDS). Enzyme replacement therapy (ERT) with recombinant human IDS, available since 2005, is currently the most appropriate treatment for this progressive, multisystemic, chronic, and life-threatening disease. Efficacy and safety of therapy with idursulfase have been assessed in several clinical trials, and confirmed in many clinical reports. Long-term follow-up of patients receiving ERT has demonstrated the importance of an early onset of treatment with idursulfase, before irreversible pathological changes occur. Intravenously administered idursulfase is not able to cross the blood–brain barrier, so neurological signs and symptoms cannot benefit from ERT, still remaining a major challenge in the treatment of MPS II. Keywords: MPS II, glycosaminoglycans, enzyme replacement therapy, ER

The ALMA view of the high redshift relation between supermassive black holes and their host galaxies

This work aims at studying the $M_{BH}-M_{dyn}$ relation of a sample of $2<z<7$ quasars by constraining their host galaxy masses through a full kinematical modelling of the cold gas kinematics thus avoiding all possible biases and effects introduced by the rough virial estimates usually adopted so far. For this purpose we retrieved public observations of $72$ quasar host galaxies observed in ${\rm [CII]_{158\mu m}}$ or ${\rm CO}$ transitions with the Atacama Large Millimeter Array (ALMA). We then selected those quasars whose line emission is spatially resolved and performed a kinematic analysis on ALMA observations. We estimated the dynamical mass of the systems by modelling the gas kinematics with a rotating disc taking into account geometrical and instrumental effects. Our dynamical mass estimates, combined with $M_{BH}$ obtained from literature and our own new ${\rm CIV}\lambda1550$ observations have allowed us to investigate the $M_{BH}/M_{dyn}$ in the early Universe. Overall we obtained a sample of $10$ quasars at $z\sim2-7$ in which line emission is detected with high SNR ($> 5-10$) and the gas kinematics is spatially resolved and dominated by ordered rotation. The estimated dynamical masses place $6$ out of $10$ quasars above the local relation yielding to a $M_{BH}/M_{dyn}$ ratios $\sim10\times$ higher than those estimated in low-$z$ galaxies. On the other hand we found that $4$ quasars at $z\sim 4-6$ have dynamical-to-BH mass ratios consistent with what is observed in early type galaxies in the local Universe.STFC and ER

Bromodomain and extraterminal domain (BET) protein inhibition hinders glioblastoma progression by inducing autophagy-dependent differentiation

Glioblastoma multiforme (GBM) is the most common and aggressive type of malignant primary brain tumor, and it is characterized by a high recurrence incidence and poor prognosis due to the presence of a highly heterogeneous mass of stem cells with self-renewal capacity and stemness maintenance ability. In recent years, the epigenetic landscape of GBM has been explored and many epigenetic alterations have been investigated. Among the investigated epigenetic abnormalities, the bromodomain and extra-terminal domain (BET) chromatin readers have been found to be significantly overexpressed in GBM. In this work, we investigated the effects of BET protein inhibition on GBM cell reprogramming. We found that the pan-BET pharmacological inhibitor JQ1 was able to promote a differentiation program in GBM cells, thus impairing cell proliferation and enhancing the toxicity of the drug Temozolomide (TMZ). Notably, the pro-differentiation capability of JQ1 was prevented in autophagy-defective models, suggesting that autophagy activation is necessary for BET protein activity in regulating glioma cell fate. Given the growing interest in epigenetic therapy, our results further support the possibility of introducing a BET-based approach in GBM clinical management

Fast Detection of a BRCA2 Large Genomic Duplication by Next Generation Sequencing as a Single Procedure: A Case Report.

The aim of this study was to verify the reliability of a next generation sequencing (NGS)-based method as a strategy to detect all possible BRCA mutations, including large genomic rearrangements. Genomic DNA was obtained from a peripheral blood sample provided by a patient from Southern Italy with early onset breast cancer and a family history of diverse cancers. BRCA molecular analysis was performed by NGS, and sequence data were analyzed using two software packages. Comparative genomic hybridization (CGH) array was used as confirmatory method. A novel large duplication, involving exons 4–26, of BRCA2 was directly detected in the patient by NGS workflow including quantitative analysis of copy number variants. The duplication observed was also found by CGH array, thus confirming its extent. Large genomic rearrangements can affect the BRCA1/2 genes, and thus contribute to germline predisposition to familial breast and ovarian cancers. The frequency of these mutations could be underestimated because of technical limitations of several routinely used molecular analysis, while their evaluation should be included also in these molecular testing. The NGS-based strategy described herein is an effective procedure to screen for all kinds of BRCA mutations

Resolving the physics of quasar Ly α nebulae (RePhyNe): I. Constraining quasar host halo masses through circumgalactic medium kinematics

Ly α nebulae ubiquitously found around z > 2 quasars can supply unique constraints on the properties of the circumgalactic medium, such as its density distribution, provided the quasar halo mass is known. We present a new method to constrain quasar halo masses based on the line-of-sight velocity dispersion maps of Ly α nebulae. By using MUSE-like mock observations obtained from cosmological hydrodynamic simulations under the assumption of maximal quasar fluorescence, we show that the velocity dispersion radial profiles of Ly α emitting gas are strongly determined by gravity and that they are thus self-similar with respect to halo mass when rescaled by the virial radius. Through simple analytical arguments and by exploiting the kinematics of He II1640 Å emission for a set of observed nebulae, we show that Ly α radiative transfer effects plausibly do not change theshape of the velocity dispersion profiles but only their normalization without breaking their self-similarity. Taking advantage of these results, we define the variable η140−200 40−100 as the ratio of the median velocity dispersion in two specifically selected annuli and derive an analytical relation between η140−200 40−100 and the halo mass which can be directly applied to observations. We apply our method to 37 observed quasar Ly α nebulae at 3 < z < 4.7 and find that their associated quasars are typically hosted by ∼1012.16 ± 0.14M haloes independent of redshift within the explored range. This measurement, which is completely independent of clustering methods, is consistent with the lowest mass estimates based on quasar autocorrelation clustering at z∼3 and with quasar-galaxies cross-correlation results

Translational Roadmap for the Organs-on-a-Chip Industry toward Broad Adoption

Organs-on-a-Chip (OOAC) is a disruptive technology with widely recognized potential to change the efficiency, effectiveness, and costs of the drug discovery process; to advance insights into human biology; to enable clinical research where human trials are not feasible. However, further development is needed for the successful adoption and acceptance of this technology. Areas for improvement include technological maturity, more robust validation of translational and predictive in vivo-like biology, and requirements of tighter quality standards for commercial viability. In this review, we reported on the consensus around existing challenges and necessary performance benchmarks that are required toward the broader adoption of OOACs in the next five years, and we defined a potential roadmap for future translational development of OOAC technology. We provided a clear snapshot of the current developmental stage of OOAC commercialization, including existing platforms, ancillary technologies, and tools required for the use of OOAC devices, and analyze their technology readiness levels. Using data gathered from OOAC developers and end-users, we identified prevalent challenges faced by the community, strategic trends and requirements driving OOAC technology development, and existing technological bottlenecks that could be outsourced or leveraged by active collaborations with academia