The chiral 5,6-cyclohexane-fused uracil ring-system: A molecular platform with promising activity against SARS-CoV-2.

The recurrent global exposure to highly challenging viral epidemics, and the still limited spectrum of effective pharmacological options step on the accelerator towards the development of new antiviral medicines. In this work we explored the anti-SARS-CoV-2 potential of a recently launched chiral ring system based on the uracil scaffold fused to carbocycle rings. The asymmetric synthesis of two generations of chiral uracil-based compounds (overall 31 different products), and their in vitro cytotoxicity and antiviral screening against wild-type SARS-CoV-2 in U87.

Successful Linkage of Electronic Medical Records and National Health Data System in Type 2 Diabetes Research: Methodological Insights and Implications.

Purpose: This study assesses success and methodological implications of linking IQVIA's Electronic Medical Records (EMR) of type 2 diabetes (T2D) patients with the National Health Data System (SNDS) database, a cornerstone process in healthcare research.

Methods: The OREOT cohort was constituted by T2D patients identified in the IQVIA EMR from 2014 to 2018 and linked indirectly to SNDS database. The EMR database contains clinical records from general practitioner consultations, representing ~2.

Doubly Metathetic NiCl-Catalyzed Coupling Between Bis(2-oxazolines) and Aldehydes: A Novel Access to Bis(ester-imine) Derivatives.

The coupling between bis(2-oxazolines) and two equivalents of aromatic aldehydes in the presence of catalytic amounts of NiCl affords an ester-imine product in synthetically useful yields. This virtually unknown, 100% atom-economic transformation involves the formal metathesis between the C=N double bond of the bis(2-oxazoline) moiety, which undergoes ring-opening, and the C=O double bond of the aldehyde. The scope of this transformation is studied, and a mechanism is proposed based on DFT calculations.

Triponderal Mass Index rather than Body Mass Index in discriminating high adiposity in Brazilian children and adolescents.

Introduction: body mass index (BMI) is used worldwide to track excess weight; however, it has limitations in predicting body fat percentage (BF%). Triponderal mass index (TMI) has been studied as an alternative indicator to predict BF%.

Objective: to compare BMI and TMI as predictors of BF% and develop TMI cutoff points for screening high adiposity in Brazilian children and adolescentes.

MRI scan with the "feed and wrap" technique and with an optimized anesthesia protocol: a retrospective analysis of a single-center experience.

Introduction: MRI examinations in the pediatric population require acquiring motionless images in the safest possible manner. At our institute, we have developed a protocol called "Good Practice" aimed at avoiding anesthesia in newborns and infants through the use of the "feed and wrap" technique, as well as preventing hospitalization for older children requiring anesthesia with an optimized sedation protocol. We evaluated this protocol in terms of patient safety, imaging quality, and parental satisfaction.

Rehabilitation after musculoskeletal injury: European perspective.

Trauma is one of the main causes of death in younger people and ongoing disability worldwide. In Europe, while there is generally good organization of trauma reception and acute treatment, rehabilitation from major musculoskeletal injuries is less well defined and provided. This article documents the diverse approaches to rehabilitation after major injury in 6 European nations.

Nucleus accumbens D1- and D2-expressing neurons control the balance between feeding and activity-mediated energy expenditure.

Accumulating evidence points to dysregulations of the Nucleus Accumbens (NAc) in eating disorders (ED), however its precise contribution to ED symptomatic dimensions remains unclear. Using chemogenetic manipulations in male mice, we found that activity of dopamine D1 receptor-expressing neurons of the NAc core subregion facilitated effort for a food reward as well as voluntary exercise, but decreased food intake, while D2-expressing neurons have opposite effects. These effects are congruent with D2-neurons being more active than D1-neurons during feeding while it is the opposite during running.

Effectiveness of patients' involvement in a medical and nursing pain education programme: a protocol for an open-label randomised controlled trial including qualitative data.

Introduction: Pain is a multidimensional experience that varies among individuals and has a significant impact on their health. A biopsychosocial approach is recommended for effective pain management; however, health professionals' education is weak on this issue. Patient involvement is a promising didactic methodology in developing a more holistic perspective, however there is a lack of reliable evidence on this topic.

What causes obesity in children and adolescents?

Objective: To present the different aspects that may be involved in the genesis and maintenance of obesity in children and adolescents.

Data Source: Narrative review of articles published in the PubMed, Scielo, Lilacs, Scopus and Google Scholar databases, using the search terms: overweight, obesity, pre-conception, prenatal, infants, schoolchildren, children, and adolescents. The search was conducted in studies written in Portuguese, English and Spanish, including narrative, integrative or systematic reviews, meta-analyses, cross-sectional, case-control and cohort studies, published between 2003 and 2023.

Phosphine-Catalyzed Domino Regio- and Stereo-Selective Hexamerization of 2-(Bromomethyl)acrylates to 1,2-Bis(cyclohexenyl)ethenyl Derivatives.

A phosphine-catalyzed domino assembly of six units of 2-bromomethyl acrylates afforded polyalkenyl adducts containing two cyclohexenyl rings. This reaction occurs under mild conditions providing the final product by formation of seven carbon-carbon bonds and four stereocenters. Experimental and computational studies support an initial dimerization of the substrate, which in turn trimerizes involving two totally regio- and stereocontrolled Diels-Alder cycloadditions.

Highly efficient morpholine-based organocatalysts for the 1,4-addition reaction between aldehydes and nitroolefins: an unexploited class of catalysts.

Many studies have demonstrated how the pyrrolidine nucleus is more efficient than the corresponding piperidine or morpholine as organocatalysts in the condensation of aldehydes with electrophiles enamine. Focussing on morpholine-enamines, their low reactivity is ascribed to the presence of oxygen on the ring and to the pronounced pyramidalisation of nitrogen, decreasing the nucleophilicity of the enamine. Thus, the selection of efficient morpholine organocatalysts appears to be a difficult challenge.

Open fractures: Current treatment perspective.

Severe open fractures present challenges to orthopaedic surgeons worldwide, with increased risks of significant complications. Although different global regions have different resources and systems, there continue to be many consistent approaches to open fracture care. Management of these complex injures continues to evolve in areas ranging from timing of initial operative debridement to the management of critical-sized bone defects.

Novel Polymyxin-Inspired Peptidomimetics Targeting the SARS-CoV-2 Spike:hACE2 Interface.

Though the bulk of the COVID-19 pandemic is behind, the search for effective and safe anti-SARS-CoV-2 drugs continues to be relevant. A highly pursued approach for antiviral drug development involves targeting the viral spike (S) protein of SARS-CoV-2 to prevent its attachment to the cellular receptor ACE2. Here, we exploited the core structure of polymyxin B, a naturally occurring antibiotic, to design and synthesize unprecedented peptidomimetics (PMs), intended to target contemporarily two defined, non-overlapping regions of the S receptor-binding domain (RBD).

Accelerated Molecular Dynamics for Peptide Folding: Benchmarking Different Combinations of Force Fields and Explicit Solvent Models.

Accelerated molecular dynamics (aMD) protocols were assessed on predicting the secondary structure of eight peptides, of which two are helical, three are β-hairpins, and three are disordered. Protocols consisted of combinations of three force fields (ff99SB, ff14SB, ff19SB) and two explicit solvation models (TIP3P and OPC), and were evaluated in two independent aMD simulations, one starting from an extended conformation, the other starting from a misfolded conformation. The results of these analyses indicate that all three combinations performed well on helical peptides.

Clinical Evolution of Preschool Picky Eater Children Receiving Oral Nutritional Supplementation during Six Months: A Prospective Controlled Clinical Trial.

Objective: To determine if oral nutritional supplementation of picky eater children has a beneficial effect in addition to nutritional guidance on anthropometric parameters, nutrient intake, appetite, physical activity, and health complications.

Methods: This is a randomized, single-blind, controlled clinical trial that included Brazilian picky eater children aged 24 to 60 months. The individuals were randomized into a control group (CG) ( = 17) and an intervention group (IG) ( = 18), and were followed up in seven meetings for 180 days (baseline plus one meeting every 30 days).

Identification of a short ACE2-derived stapled peptide targeting the SARS-CoV-2 spike protein.

The design and synthesis of a series of peptide derivatives based on a short ACE2 α-helix 1 epitope and subsequent [i - i+4] stapling of the secondary structure resulted in the identification of a 9-mer peptide capable to compete with recombinant ACE2 towards Spike RBD in the micromolar range. Specifically, SARS-CoV-2 Spike inhibitor screening based on colorimetric ELISA assay and structural studies by circular dichroism showed the ring-closing metathesis cyclization being capable to stabilize the helical structure of the 9-mer HEAEDLFYQ epitope better than the triazole stapling via click chemistry. MD simulations showed the stapled peptide being able not only to bind the Spike RBD, sterically interfering with ACE2, but also showing higher affinity to the target as compared to parent epitope.

Non-Conventional Peptide Self-Assembly into a Conductive Supramolecular Rope.

Structures composed of alternating α and β amino acids can give rise to peculiar secondary structural motifs, which could self-assemble into complex structures of controlled geometries. This work describes the self-assembly properties of an α,β-peptide, containing three units of H2-(2-F-Phe)-h-PheGly-OH, able to self-organize on surfaces into a fascinating supramolecular rope. This material was characterized by AFM, electronic conduction and fluorescence measurements.

Expanding the knowledge around antitubercular 5-(2-aminothiazol-4-yl)isoxazole-3-carboxamides: Hit-to-lead optimization and release of a novel antitubercular chemotype via scaffold derivatization.

Tuberculosis is one of the deadliest infectious diseases in the world, and the increased number of multidrug-resistant and extensively drug-resistant strains is a reason for concern. We have previously reported a series of substituted 5-(2-aminothiazol-4-yl)isoxazole-3-carboxamides with growth inhibitory activity against Mycobacterium tuberculosis strains and low propensity to be substrate of efflux pumps. Encouraged by these preliminary results, we have undertaken a medicinal chemistry campaign to determine the metabolic fate of these compounds and to delineate a reliable body of Structure-Activity Relationships.

Decellularized esophageal tubular scaffold microperforated by quantum molecular resonance technology and seeded with mesenchymal stromal cells for tissue engineering esophageal regeneration.

Current surgical options for patients requiring esophageal replacement suffer from several limitations and do not assure a satisfactory quality of life. Tissue engineering techniques for the creation of customized "self-developing" esophageal substitutes, which are obtained by seeding autologous cells on artificial or natural scaffolds, allow simplifying surgical procedures and achieving good clinical outcomes. In this context, an appealing approach is based on the exploitation of decellularized tissues as biological matrices to be colonized by the appropriate cell types to regenerate the desired organs.

Non-invasive treatment of sigmoid volvulus in a child. The role of the endoscopist.

Sigmoid volvulus (SV) is a rare cause of intestinal obstruction in children. Its varied presentation and rapid progression engender a high risk of morbidity and mortality. We report two cases of SV in teenage boys.

Overview of fracture liaison services in the UK and Europe: standards, model of care, funding, and challenges.

Fragility fractures represent a growing global problem, including in the United Kingdom and European countries. Reports demonstrate the benefits of national guidance and organized fragility fracture programs through fracture liaison services to deliver care to patients who sustain these injuries. The challenge of assembling multidisciplinary teams, providing routine screening of appropriate patients, and monitoring therapies where there is a known compliance problem, remains an obstacle to the success of fragility fracture treatment programs to all.

Anthropometric Indicators of Body Composition Associated With Lipid and Glycemic Profiles in Overweight Brazilian Children and Adolescents From 2008 to 2020.

Background: Anthropometric indicators have been used to predict health problems. The objective was to determine which indicators present better correlation with dyslipidemia, hyperglycemia and peripheral insulin resistance, as well as the cutoff points capable of predicting lipid and glycemic alterations in Brazilian children and adolescents.

Methods: A cross-sectional study conducted with 568 overweight individuals, aged between 5 and 18 years, living in Southeast and South Brazilian regions, submitted to anthropometric and body composition evaluation by bioimpedance, in addition to fasting laboratory tests [total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-c), high-density lipoprotein cholesterol (HDL-c), fasting glycemia, and homeostasis model assessment-insulin resistance (HOMA-IR)].

Modular synthesis of 2,4-diaminoanilines as CNS drug-like non-covalent inhibitors of asparagine endopeptidase.

Asparagine endopeptidase (AEP), also called legumain, is a pH-dependent endolysosomal cysteine protease that cleaves its substrates after asparagine residues. Recent studies showed that it possesses δ-secretase activity and that it is implicated in numerous neurological diseases such as Alzheimer's disease (AD). Following evidence of aryl-morpholines as useful asparagine endopeptidase inhibitors, a series of morpholinoanilines with diverse substituents at ortho position were synthesized in view of improving the potency and scope of this molecular scaffold, allowing to identify ethyl 2-isonipecotate-4-morpholinoaniline possessing inhibition potency in the nanomolar range.