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

Context. The existence of tight correlations between supermassive black holes (BHs) and their host galaxies' properties in the local Universe suggests a closely linked evolution. Investigating these relations up to the high redshifts (z ≳  6) is crucial in order to understand the interplay between star formation and BH growth across the cosmic time and to set constraints on galaxy formation and evolution models. In this work, we focus on the relation between BH mass (MBH) and the dynamical mass (Mdyn) of the host galaxy. Aims. Previous works suggest an evolution of the MBH-Mdyn relation with redshift indicating that BH growth precedes the galaxy mass assembly during their co-evolution at z  >   3. However, dynamical galaxy masses at high redshift are often estimated through the virial theorem, thus introducing significant uncertainties. Within the scope of this work, our aim is to study the MBH-Mdyn relation of a sample of 2  <   z  <   7 quasars by constraining their galaxy masses through a full kinematical modelling of the cold gas kinematics, thus avoiding all possible biases and effects introduced by the rough estimates usually adopted so far. Methods. For this purpose, we retrieved public observations of 72 quasar host galaxies observed in [CII]158  μm or 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 MBH obtained from literature and our own new CIVλ1550 observations allowed us to investigate the MBH/Mdyn in the early Universe. Results. Overall, we obtained a sample of ten quasars at z  ∼  2-7, in which line emission is detected with high S/N (≳ 5-10) and the gas kinematics are spatially resolved and dominated by ordered rotation. The estimated dynamical masses place six out of ten quasars above the local relation yielding to MBH/Mdyn ratios ∼10× higher than those estimated in low-z galaxies. On the other hand, we found that four quasars at z  ∼  4-6 have dynamical-to-BH-mass ratios consistent with what is observed in early-type galaxies in the local Universe

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

Report and follow-up on two new patients with congenital mesoblastic nephroma

Background: Tumors are rare in neonatal age. Congenital mesoblastic nephroma (CMN) is a usually benign renal tumor observed at birth, or in the first months of life. It may also be identified prenatally and associated with polyhydramnios leading to preterm delivery. Effective treatment is surgical in most cases, consisting in total nephrectomy. In literature, very few studies report on the neonatal management of such a rare disease, and even less are those describing its uncommon complications. Cases presentation: We report on two single-center newborns affected with CMN. The first patient is a preterm female baby, born at 30+ 1 weeks of gestation (WG) due to premature labor, with prenatal (25 WG) identification of an intra-abdominal fetal mass associated with polyhydramnios. Once obtained the clinical stability, weight gain, instrumental (computed tomography, CT, showing a 4.8 × 3.3&nbsp;cm left renal neoformation) and histological/molecular characterization of the lesion (renal needle biopsy picture of classic CMN with ETV6-NTRK3 translocation), a left nephrectomy was performed at 5 weeks of chronological age. The following clinical course was complicated by intestinal obstruction due to bowel adherences formation, then by an enterocutaneous fistula, requiring multiple surgical approaches including transitory ileo- and colostomy, before the conclusive anastomoses intervention. The second patient is a 17-day-old male term baby, coming to our observation due to postnatal evidence of palpable left abdominal mass (soon defined through CT, showing a 7.5 × 6.5&nbsp;cm neoformation in the left renal lodge), feeding difficulties and poor weight gain. An intravenous diuretic treatment was needed due to the developed hypertension and hypercalcemia, which regressed after the nephrectomy (histological diagnosis of cellular CMN with ETV6-NTRK3 fusion) performed at day 26. In neither case was chemotherapy added. Both patients have been included in multidisciplinary follow-up, they presently show regular growth and neuromotor development, normal renal function and no local/systemic recurrences or other gastrointestinal/urinary disorders. Conclusions: The finding of a fetal abdominal mass should prompt suspicion of CMN, especially if it is associated with polyhydramnios; it should also alert obstetricians and neonatologists to the risk of preterm delivery. Although being a usually benign condition, CMN may be associated with neonatal systemic-metabolic or postoperative complications. High-level surgical expertise, careful neonatological intensive care and histopathological/cytogenetic-molecular definition are the cornerstones for the optimal management of patients. This should also include an individualized follow-up, oriented to the early detection of any possible recurrences or associated anomalies and to a better quality of life of children and their families

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

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

Dieta com baixo teor de FODMAPs para distúrbios de dor abdominal funcional em crianças: revisão crítica do conhecimento atual (Low FODMAPs diet for functional abdominal pain disorders in children: critical review of current knowledge)

Objective: This narrative review aimed to provide practitioners a synthesis of the current knowledge on the role of a low Fermentable Oligosaccharides Disaccharides Monosaccharides and Polyols diet in reducing symptoms associated with functional abdominal pain disorders in children. This review is focused on the pathophysiology, efficacy and criticism of low Fermentable Oligosaccharides Disaccharides Monosaccharides and Polyols diet in children. / Sources: Cochrane Database, Pubmed and Embase were searched using specific terms for Fermentable Oligosaccharides Disaccharides Monosaccharides and Polyols diet interventions and functional abdominal pain disorders. / Summary of the findings: In children, only one Randomized Control Trial and one open‐label study reported positive results of low Fermentable Oligosaccharides Disaccharides Monosaccha‐rides and Polyols diet; one Randomized Control Trial showed exacerbation of symptoms with fructans in children with Irritable Bowel Syndrome; no effect was found for the lactose‐free diet whilst fructose‐restricted diets were effective in 5/6 studies. / Conclusions: In children there are few trials evaluating low Fermentable Oligosaccharides Disaccharides Monosaccharides and Polyols in functional abdominal pain disorders, with encour‐aging data on the therapeutic efficacy particularly of fructose‐restricted diet. Additional effort sare still needed to fill this research gap and clarify the most efficient way for tailoring dietary restrictions based on the patient's tolerance and/or identification of potential biomarkers of low Fermentable Oligosaccharides Disaccharides Monosaccharides and Polyols efficacy, to maintain nutritional adequacy and to simplify the adherence to diet by labeling FermentableOligosaccharides Disaccharides Monosaccharides and Polyols content in commercial products

Comment on 'Cancer genetic counselling' by P. Mandich et al.

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