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Ureterocele is a cystic dilatation of the intravesical submucosal ureter, with an obstructed orifice. Endoscopic treatment is one of the most common option for surgical treatment. In intravesical ureterocele, the punctures must be made just above the junction between the ureterocele and the bladder floor. We commonly use a 8–9.8 Fr cystoscope, with a 5 Fr working channel, a metallic needle for bulking agent injection 3.7 Fr. In selected cases we also use electric or laser probes to decompress the ureterocele. When evidence of decompression is verified and vesicoureteral reflux is excluded, antibiotic prophylaxis is stopped. If, despite decompression, a large ureterocele is subsequently obstructing the bladder neck a surgical excision is necessary. Forty-four patients (92%) were treated endoscopically. Ureterocele puncture was performed with a metallic needle for bulking agent injection in 30 cases (63%), with a laser fiber in 7 cases (15%), with an electrified ureteral catheter in 4 cases (8%), and with Bugbee in 3 cases (6%). A success rate after one procedure was achieved in 40 children (83%). Adequate opening of the ureterocele with complete decompression of the reno-ureteral system is the goal of endoscopic treatment. An overaggressive incision or puncture could result in an increased chance of secondary vesicoureteral reflux. [ABSTRACT FROM AUTHOR]

Background: Restorative proctocolectomy (RPC) with ileal pouch-anal anastomosis (IPAA) is the gold standard surgical treatment for patients with ulcerative colitis (UC) unresponsive to medical therapy and those with familial adenomatous polyposis. Robotic IPAA is a safe and feasible option for the surgical treatment of UC in children. The feasibility of IPAA without ileostomy has been demonstrated in adult in the modified two-stage approach. Aim: The aim of the study was to examine feasibility, outcomes, and complications of robotic modified two-stage approach for RPC with IPAA in pediatric patients comparing it with robotic three-stage approach. Methods: All patients aged 4-18 years who underwent operative treatment for medically refractory UC were included. Demographic and clinical features, age at colectomy and at reconstructive surgery, intraoperative details and complications, and postoperative outcomes were analyzed. Results: Thirteen patients were included in the study (6 males, 7 females). Ileostomy was fashioned in 8 patients at the time of RPC and IPAA (Group 1); in 5 patients the bowel continuity was reintegrated at the time of IPAA (Group 2). No intraoperative complications and no conversions were recorded. One patient of Group 1 had a postoperative pouch complication. The 5 patients who underwent a two-stage procedure did not show short-term complications. No statistical differences were found between the groups in short-term ( P = .48) and long-term complications ( P = .07). Conclusions: Modified two-stage IPAA is a safe and feasible option in pediatric patients with UC, and RALS offers advantages over other techniques for the precision of rectal dissection and ileo-anal anastomosis.

Background: Advanced Hybrid Closed-Loop system (AHCL) has profoundly changed type 1 diabetes therapy. This study primarily aimed to assess the impact on Glycemia Risk Index (GRI) and other continuous glucose monitoring (CGM) metrics when switching from one of four insulin strategies to AHCL in type 1 adult patients., Methods: A single-center, retrospective pre/post observational study; 198 patients (age 44.4 ± 12.7 years, 115 females/83 males, diabetes duration 24.7 ± 11.6 years, HbA1c 7.4 ± 1%), treated with different insulin therapies (MDI, CSII, SAP with PLGS, HCL) were assessed before and after switching to an AHCL (MiniMed 780G, Diabeloop Roche, Tandem Control-IQ) at 1, 3, 6, and 12 months. Mixed-effects multivariable regression models were used to estimate the mean pre/post variations at different time points, adjusted for potential confounders., Results: A month after the switch, there was an improvement in CGM metrics and HbA1c for all patients: GRI -10.7, GMI -0.27%, CV -2.1%, TAR >250 -3.7%, TAR 180-250 -5.6%, TIR + 9.7%, HbA1c -0.54% (all p < 0.001). This improvement was maintained throughout the observational period (at 3, 6, and 12 months, with all p-values < 0.001). When improvements across the 780, Diabeloop, and Tandem CIQ devices were compared: Diabeloop demonstrated significantly better performance in terms of GRI, GMI, CV, TAR >250 at T1 (for all p < 0.01); 780 recorded highest average decrease in TAR 180-250 (p = 0.020), while Tandem achieved the most significant reduction in TBR 54-69 (p = 0.004)., Conclusions: Adopting an AHCL leads to a rapid and sustained improvement in GRI and other parameters of metabolic control for up to a year, regardless of prior insulin therapies, baseline conditions or brands., (© 2024. The Author(s).)

Cesarean section is considered a possible trigger of atopy and gut dysbiosis in newborns. Bifidobacteria, and specifically B. bifidum , are thought to play a central role in reducing the risk of atopy and in favoring gut eubiosis in children. Nonetheless, no trial has ever prospectively investigated the role played by this single bacterial species in preventing atopic manifestations in children born by cesarean section, and all the results published so far refer to mixtures of probiotics. We have therefore evaluated the impact of 6 months of supplementation with B. bifidum PRL2010 on the incidence, in the first year of life, of atopy, respiratory tract infections, and dyspeptic syndromes in 164 children born by cesarean (versus 249 untreated controls). The results of our multicenter, randomized, and controlled trial have shown that the probiotic supplementation significantly reduced the incidence of atopic dermatitis, upper and lower respiratory tract infections, and signs and symptoms of dyspeptic syndromes. Concerning the gut microbiota, B. bifidum supplementation significantly increased α-biodiversity and the relative values of the phyla Bacteroidota and Actinomycetota, of the genus Bacteroides , Bifidobacterium and of the species B. bifidum and reduced the relative content of Escherichia / Shigella and Haemophilus . A 6-month supplementation with B. bifidum in children born by cesarean section reduces the risk of gut dysbiosis and has a positive clinical impact that remains observable in the following 6 months of follow-up.

A large library of saccharin and acesulfame derivatives has been synthesised and evaluated against four isoforms of human carbonic anhydrase, the two off-targets hCA I/II and the tumour related isoforms hCA IX/XII. Different strategies of scaffold modification have been attempted on both saccharin as well as acesulfame core leading to the obtainment of 60 compounds. Some of them exhibited inhibitory activity in the nanomolar range, albeit some of the performed changes led to either micromolar activity or to its absence, against hCA IX/XII. Molecular modelling studies focused the attention on the binding mode of these compounds to the enzyme. The proposed inhibition mechanism is the anchoring to zinc-bound water molecule. Docking studies along with molecular dynamics also underlined the importance of the compounds flexibility (e.g. achieved through the insertion of methylene group) which favoured potent and selective hCA inhibition.

Introduction : Antimicrobial resistance is a worldwide problem accounting for the reduction or in some cases absence of drugs effectiveness normally used in infections treatment. In the light of the even more spread ability of microbials to develop resistance, there is an urgent necessity to find novel and alternative routes to fight infections. Natural compounds or extracts can be a valid alternative either as monotherapy or as adjuvant in order to improve the effectiveness of the failing drugs. Areas covered : This review provides a comprehensive update (2018-2020) on the development state of innovative antimicrobial agents based on natural compounds and extracts, also describing their compositions, methods of production and use, mechanism of action, along with anti-microbial data when available. Expert opinion : Owing to the pivotal role that natural compounds often cover in the finding of novel drugs, their in-depth analysis could pave the way to the discovery of new antimicrobial agents. Most of the alternative approaches reported in this short review were validated through in vitro and in vivo (animal as well as human) models. The employment of natural derived compounds and extracts, alone or in combination with classical antimicrobial drugs, as antimicrobial agents could represent an important achievement to challenge pathogens resistant mechanisms.

Human tyrosinase (hTYR) and tyrosinase-related protein 1 (hTYRP1) are closely-related enzymes involved in the synthesis of melanin, which are selectively expressed in melanocytes and, in a pathological context, in melanoma lesions. We used a previously described tyrosinase inhibitor (Thiamidol™) and DNA-encoded library technology for the discovery of novel hTYR and hTYRP1 ligands, that could be used as vehicles for melanoma targeting. Performing de novo selections with DNA-encoded libraries, we discovered novel ligands capable of binding to both hTYR and hTYRP1. More potent ligands were obtained by multimerizing Thiamidol™ moieties, leading to homotetrameric structures that avidly bound to melanoma cells, as revealed by flow cytometry. These findings suggest that melanoma lesions may, in the future, be targeted not only by monoclonal antibody reagents but also by small organic ligands., Competing Interests: The authors declare the following competing financial interest(s): D. N. is a cofounder and shareholder of Philochem AG., (This journal is © The Royal Society of Chemistry.)

A large library of derivatives based on the scaffold of 2-(benzylsulfinyl)benzoic acid were synthesised and tested as atypical inhibitors against four different isoforms of human carbonic anhydrase (hCA I, II, IX and XII, EC 4.2.1.1). The exploration of the chemical space around the main functional groups led to the discovery of selective hCA IX inhibitors in the micromolar/nanomolar range, thus establishing robust structure-activity relationships within this versatile scaffold. HPLC separation of some selected chiral compounds and biological evaluation of the corresponding enantiomers was performed along with molecular modelling studies on the most active derivatives.

A series of benzo[ b ]thiophen-3-ols were synthesised and investigated as potential human monoamine oxidase (hMAO) inhibitors in vitro as well as ex vivo in rat cortex synaptosomes by means of evaluation of 3,4-dihydroxyphenylacetic acid/dopamine (DOPAC/DA) ratio and lactate dehydrogenase (LDH) activity. Most of these compounds possessed high selectivity for the MAO-B isoform and a discrete antioxidant and chelating potential. Molecular docking studies of all the compounds underscored potential binding site interactions suitable for MAO inhibition activity, and suggested structural requirements to further improve the activity of this scaffold by chemical modification of the aryl substituents. Starting from this heterocyclic nucleus, novel lead compounds for the treatment of neurodegenerative disease could be developed.

New N -acetyl/ N -thiocarbamoylpyrazoline derivatives were designed and synthesized in high yields to assess their inhibitory activity and selectivity against human monoamine oxidase A and B. The most important chiral compounds were separated into their single enantiomers and tested. The impact of the substituents at N1, C3 and C5 positions as well the influence of the configuration of the C5 on the biological activity were analyzed. Bulky aromatic groups at C5 were not tolerated. p -Prenyloxyaryl moiety at C3 oriented the selectivity toward the B isoform. The results were also corroborated by molecular modelling studies providing new suggestions for the synthesis of privileged structures to serve as lead compounds for the treatment of mood disorders and neurodegenerative diseases., Competing Interests: The authors declare no competing financial interests.