Direct Photocatalyzed Hydrogen Atom Transfer (HAT) for Aliphatic C-H Bonds Elaboration

[Image: see text] Direct photocatalyzed hydrogen atom transfer (d-HAT) can be considered a method of choice for the elaboration of aliphatic C–H bonds. In this manifold, a photocatalyst (PC(HAT)) exploits the energy of a photon to trigger the homolytic cleavage of such bonds in organic compounds. Selective C–H bond elaboration may be achieved by a judicious choice of the hydrogen abstractor (key parameters are the electronic character and the molecular structure), as well as reaction additives. Different are the classes of PCs(HAT) available, including aromatic ketones, xanthene dyes (Eosin Y), polyoxometalates, uranyl salts, a metal-oxo porphyrin and a tris(amino)cyclopropenium radical dication. The processes (mainly C–C bond formation) are in most cases carried out under mild conditions with the help of visible light. The aim of this review is to offer a comprehensive survey of the synthetic applications of photocatalyzed d-HAT

Polymer Shaped Punches Produces with Fused Filament Fabrication to Improve Cup Accuracy in Sheet Metal Forming

Rapid tooling has become an effective solution for reducing time and costs in tool production. In sheet metal forming, polymer tools produced via additive manufacturing offer performance comparable to traditional tools. However, a key challenge in this area is compensating for the radial expansion of polymer tools during the forming process, which leads to reduced accuracy in the produced parts and limits the achievable forming depth. To address this issue, the authors of this study proposed a novel punch design aimed at containing radial expansion, thereby enabling greater drawing depth and improved part accuracy. Different punch geometries were designed with a re-entrant angle varying between 150° and 180°. Numerical simulations were conducted to evaluate the optimal geometry, identifying the 160° angle as the best option to compensate for radial expansion and reduce punch load. Experimental tests were then performed to verify the numerical results, demonstrating the potential of this new design producing cups with higher drawing depth and best radial accuracy

Acute pain management in children: A survey of Italian pediatricians

Background: Current guidelines recommend assessing and relieving pain in all children and in all instances; yet, in clinical practice, management is frequently suboptimal. We investigated the attitude of Italian family pediatricians towards the evaluation and treatment of different types of acute pain in children aged 7-12 years. Methods: This is a cross-sectional study based on a 17-question survey accessible online from October 2017 to October 2018. Responders had to describe cases of children suffering from any type of acute pain among headache, sore throat, musculoskeletal/post-traumatic pain, and earache. Children's characteristics, pain assessment modalities and therapeutic approaches were queried. The following tests were used: Z-proportion to evaluate the distribution of categorical data; chi-squared and Kruskall-Wallis to explore data heterogeneity across groups; Mann-Whitney for head-to-head comparisons. Results: Overall, 929 pediatricians presented 6335 cases uniformly distributed across the types examined. Pain was more frequently of moderate intensity (42.2%, P < 0.001) and short duration (within some days: 98.4%, P < 0.001). Only 50.1% of responders used an algometric scale to measure pain and 60.5% always prescribed a treatment. In children with mild-moderate pain (N = 4438), the most commonly used first-line non-opioids were ibuprofen (53.3%) and acetaminophen (44.4%). Importantly, a non-recommended dosage was prescribed in only 5.3% of acetaminophen-treated cases (overdosing). Among the misconceptions emerged, there were the following: I) ibuprofen and acetaminophen have different efficacy and safety profiles (when choosing the non-opioid, effectiveness weighted more for ibuprofen [79.7% vs 74.3%, P < 0.001] and tolerability for acetaminophen [74.0% vs 55.4%, P < 0.001]); ii) ibuprofen must be taken after meals to prevent gastric toxicities (52.5%); ibuprofen and acetaminophen can be used combined/alternated for persisting mild-moderate pain (16.1%). In case of moderate-severe pain not completely controlled by opioids, ibuprofen and acetaminophen were the most used add-on medications, with ibuprofen being much more prescribed than acetaminophen (65.2% vs 23.7%, respectively) overall and in all pain types. Conclusions: Several gaps exist between the current practice of pain assessment and treatment and recommendations. Further efforts are needed to raise awareness and improve education on the possible exposure of the child to short- A nd long-term consequences in case of suboptimal pain management

Efficacy of adalimumab as second-line therapy in a pediatric cohort of crohn’s disease patients who failed infliximab therapy: The Italian society of pediatric gastroenterology, hepatology, and nutrition experience

Background: Adalimumab (Ada) treatment is an available option for pediatric Crohn’s disease (CD) and the published experience as rescue therapy is limited. Objectives: We investigated Ada efficacy in a retrospective, pediatric CD cohort who had failed previous infliximab treatment, with a minimum follow-up of 6 months. Methods: In this multicenter study, data on demographics, clinical activity, growth, laboratory values (CRP) and adverse events were collected from CD patients during follow-up. Clinical remission (CR) and response were defined with Pediatric CD Activity Index (PCDAI) score ≤10 and a decrease in PCDAI score of ≥12.5 from baseline, respectively. Results: A total of 44 patients were consecutively recruited (mean age 14.8 years): 34 of 44 (77%) had active disease (mean PCDAI score 24.5) at the time of Ada administration, with a mean disease duration of 3.4 (range 0.3–11.2) years. At 6, 12, and 18 months, out of the total of the enrolled population, CR rates were 55%, 78%, and 52%, respectively, with a significant decrease in PCDAI scores (P<0.01) and mean CRP values (mean CRP 5.7 and 2.4 mL/dL, respectively; P<0.01) at the end of follow-up. Steroid-free remission rates, considered as the total number of patients in CR who were not using steroids at the end of this study, were 93%, 95%, and 96% in 44 patients at 6, 12, and 18 months, respectively. No significant differences in growth parameters were detected. In univariate analysis of variables related to Ada efficacy, we found that only a disease duration >2 years was negatively correlated with final PCDAI score (P<0.01). Two serious adverse events were recorded: 1 meningitis and 1 medulloblastoma. Conclusion: Our data confirm Ada efficacy in pediatric patients as second-line biological therapy after infliximab failure. Longer-term prospective data are warranted to define general effectiveness and safety in pediatric CD patients

Photoinduced Halogen-Atom Transfer by N-Heterocyclic Carbene-Ligated Boryl Radicals for C(sp³)-C(sp³) Bond Formation

Herein, we present a comprehensive study on the use of N-heterocyclic carbene (NHC)-ligated boryl radicals to enable C(sp3)–C(sp3) bond formation under visible-light irradiation via Halogen-Atom Transfer (XAT). The methodology relies on the use of an acridinium dye to generate the boron-centered radicals from the corresponding NHC-ligated boranes via single-electron transfer (SET) and deprotonation. These boryl radicals subsequently engage with alkyl halides in an XAT step, delivering the desired nucleophilic alkyl radicals. The present XAT strategy is very mild and accommodates a broad scope of alkyl halides, including medicinally relevant compounds and biologically active molecules. The key role of NHC-ligated boryl radicals in the operative reaction mechanism has been elucidated through a combination of experimental, spectroscopic, and computational studies. This methodology stands as a significant advancement in the chemistry of NHC-ligated boryl radicals, which had long been restricted to radical reductions, enabling C–C bond formation under visible-light photoredox conditions

Gremlin is a novel agonist of the major pro-angiogenic receptor VEGFR2

The bone morphogenic protein antagonist gremlin is expressed during embryonic development and under different pathologic conditions, including cancer. Gremlin is a proangiogenic protein belonging to the cystine-knot superfamily that includes transforming growth factor-β proteins and the angiogenic vascular endothelial growth factors (VEGFs). Here, we demonstrate that gremlin binds VEGF receptor-2 (VEGFR2), the main transducer of VEGF-mediated angiogenic signals, in a bone morphogenic protein-independent manner. Similar to VEGF-A, gremlin activates VEGFR2 in endothelial cells, leading to VEGFR2-dependent angiogenic responses in vitro and in vivo. Gremlin thus represents a novel proangiogenic VEGFR2 agonist distinct from the VEGF family ligands with implications in vascular development, angiogenesis-dependent diseases, and tumor neovascularization

18F-choline PET/CT and PET/MRI in primary and recurrent hyperparathyroidism: a systematic review of the literature

The aims of the present systematic review were to: (1) assess the role of 18F-fluorocholine (FCH) positron emission tomography (PET) with computed tomography (CT) and PET with magnetic resonance imaging (MRI) in patients with biochemically known hyperparathyroidism; (2) compare the diagnostic performance of FCH PET/CT or PET/MRI with conventional morphological and functional imaging. A literature search until December 2019 was performed in the PubMed, Scopus and Web of Science databases, using the terms “choline” AND “PET” AND “hyperparathyroidism”. The search was conducted with and without the addition of filters (e.g., language: English only; type of article: original article; subjects: humans only) and selecting only articles published in the last 5 years. Twenty-three articles and 1112 patients were considered. Different FCH PET/CT acquisition protocols were adopted across the studies, using dynamic, early or delayed scans. FCH PET/CT proved more accurate than ultrasonography (US) or 99mTc-sestamibi single-photon emission tomography (SPET). PET/MRI also seemed to be more accurate than MRI alone in detecting benign parathyroid lesions. FCH PET/CT is more accurate than conventional morphological and functional imaging modalities (US or SPET) for the detection of benign parathyroid lesions. It could, therefore, be a reliable tool in both primary and recurrent hyperparathyroidism

Defective iron supply for erythropoiesis and adequate endogenous erythropoietin production in the anemia associated with systemic-onset juvenile chronic arthritis.

peer reviewedSystemic-onset juvenile chronic arthritis (SoJCA) is associated with high levels of circulating interleukin-6 (IL-6) and is frequently complicated by severe microcytic anemia whose pathogenesis is unclear. Therefore, we studied 20 consecutive SoJCA patients with hemoglobin (Hb) levels <12 g/dL, evaluating erythroid progenitor proliferation, endogenous erythropoietin production, body iron status, and iron supply for erythropoiesis. Hb concentrations ranged from 6.5 to 11.9 g/dL. Hb level was directly related to mean corpuscular volume (r = .82, P < .001) and inversely related to circulating transferrin receptor (r = -.81, P < .001) suggesting that the severity of anemia was directly proportional to the degree of iron-deficient erythropoiesis. Serum ferritin ranged from 18 to 1,660 microgram/L and was unrelated to Hb level. Bone marrow iron stores wore markedly reduced in the three children investigated, and they also showed increased serum transferrin receptor and normal-to-high serum ferritin. All 20 patients had elevated IL-6 levels and normal in vitro growth of erythroid progenitors. Endogenous erythropoietin (epo) production was appropriate for the degree of anemia as judged by both the observed to predicted log (serum epo) ratio 10.95 +/- 0.12) and a comparison of the serum epo-Hb regression found in these subjects with that of thalassemia patients. Multiple regression analysis showed that serum transferrin receptor was the parameter most closely related to hemoglobin concentration: variation in circulating transferrin receptor explained 61% of the variation in Hb level (P < .001). In 10 severely anemic patients, amelioration of anemia following intravenous iron administration resulted in normalization of serum transferrin receptor. Defective iron supply to the erythron rather than blunted epo production is the major cause of the microcytic anemia associated with SoJCA. A true body-iron deficiency caused by decreased iron absorption likely complicates long-lasting inflammation in the most anemic children, and this can be recognized by high serum transferrin receptor levels. Although oral iron is of no benefit, intravenous iron saccharate is a safe and effective means for improving iron availability for erythropoiesis and correcting this anemia. Thus, while chronically high endogenous IL-6 levels do not appear to blunt epo production, they are probably responsible for the observed abnormalities in iron metabolism. Anemia of chronic disease encompasses a variety of anemic conditions whose peculiar features may specifically correlate with the type of cytokine(s) predominantly released