Robotics Education in STEM Units: Breaking Down Barriers in Rural Multigrade Schools.

We report a novel proposal for reducing the digital divide in rural multigrade schools, incorporating knowledge of robotics with a STEM approach to simultaneously promote curricular learning in mathematics and science in several school grades. We used an exploratory qualitative methodology to implement the proposal with 12 multigrade rural students. We explored the contribution of the approaches to the promotion of curricular learning in mathematics and science and the perceptions of using robotics to learn mathematics and science. As data collection techniques, we conducted focus groups and semi-structured interviews with the participants and analyzed their responses thematically. We concluded that the proposal could contribute to meeting the challenges of multigrade teaching. Our findings suggest that the proposal would simultaneously promote the development of curricular learning in mathematics and science in several school grades, offering an alternative for addressing various topics with different degrees of depth.

Strategies for the Biofunctionalization of Straining Flow Spinning Regenerated Bombyx mori Fibers.

High-performance regenerated silkworm (Bombyx mori) silk fibers can be produced efficiently through the straining flow spinning (SFS) technique. In addition to an enhanced biocompatibility that results from the removal of contaminants during the processing of the material, regenerated silk fibers may be functionalized conveniently by using a range of different strategies. In this work, the possibility of implementing various functionalization techniques is explored, including the production of fluorescent fibers that may be tracked when implanted, the combination of the fibers with enzymes to yield fibers with catalytic properties, and the functionalization of the fibers with cell-adhesion motifs to modulate the adherence of different cell lineages to the material. When considered globally, all these techniques are a strong indication not only of the high versatility offered by the functionalization of regenerated fibers in terms of the different chemistries that can be employed, but also on the wide range of applications that can be covered with these functionalized fibers.

Boosting Molecular Complexity with O2 : Iron-Catalysed Oxygenation of 1-Arylisochromans through Dehydrogenation, Csp3 -O Bond Cleavage and Hydrogenolysis.

Oxidative cleavage of the Csp3 -O bond in 1-arylisochromans with stoichiometric oxidants, such as CrO3 /H2 SO4 , has been practiced for decades in synthetic chemistry. Herein, we report that a structurally well-defined FeII -pyridyl(bis-imidazolidine) catalyst promotes the aerobic oxygenation of 1-arylisochromans, affording highly selectively 2-(hydroxyethyl)benzophenones, compounds of potential for neuroprotective agents. Key intermediates have been isolated, indicating that the reaction proceeds through dehydrogenative oxygenation of the isochromans at the 1-position, Csp3 -O bond cleavage at the iron centre and hydrogenolysis of the resulting Fe-O bond with the H2 generated from the dehydrogenation step. In the absence of H2 but under iron catalysis, the peroxide intermediate is converted into an unexpected ketal compound, which transfers into a 2-(hydroxyethyl)benzophenone when both O2 and H2 are admitted. The unique ability of the iron catalyst for oxygenation and hydrogenation in the same catalytic process under mild conditions allows for the stepwise preparation of a variety of isolable oxygenated products on a preparative scale, circumventing the need for using wasteful and/or toxic oxidants.

A morphological database for 606 Colombian bird species.

Colombia is the country with the highest bird diversity in the world. Despite active research in ornithology, compelling morphological information of most bird species is still sparse. However, morphological information is the baseline to understand how species respond to environmental variation and how ecosystems respond to species loss. As part of a national initiative, the Instituto Alexander von Humboldt in collaboration with 12 Colombian institutions and seven biological collections, measured up to 15 morphological traits of 9,892 individuals corresponding to 606 species: 3,492 from individuals captured in field and 6,400 from museum specimens. Species measured are mainly distributed in high Andean forest, páramo, and wetland ecosystems. Seven ornithological collections in Colombia and 18 páramo complexes throughout Colombia were visited from 2013 to 2015. The morphological traits involved measurements from bill (total and exposed culmen, bill width and depth), wing (length, area, wingspan, and the distance between longest primary and longest secondary), tail (length and shape), tarsus (length), hallux (length and claw hallux), and mass. The number of measured specimens per species was variable, ranging from 1 to 321 individuals with a median of four individuals per species. Overall, this database gathered morphological information for >30% of Colombian bird diversity. No copyright, proprietary, or cost restrictions apply; the data should be cited appropriately when used.

Childhood Craniopharyngioma: A 22-Year Challenging Follow-Up in a Single Center.

Craniopharyngioma is a sellar/suprasellar benign tumor whose aggressiveness may imply in endocrine disturbances (hypothalamic obesity and hormone deficiencies). Fifty-seven patients were evaluated according to clinical characteristics, hypothalamic involvement, type of treatment, anthropometric variables, adiposity indexes (body mass index Z score category at diagnosis and post-treatment, total body fat, visceral adipose tissue, and metabolic syndrome components) and analyzed through multiple regression and logistic models. Patients were stratified according to growth hormone deficiency and recombinant human growth hormone use. Mean ages at diagnosis and at study evaluation were 9.6 and 16.6 years old, respectively. A set of 43/57 (75.4%) patients presented with important hypothalamic involvement, 24/57 (42.1%) received surgical treatment and cranial radiotherapy, and 8/57 (14%) interferon-α exclusively. Fifty-five patients (96.5%) were considered growth hormone deficient, and 26/57 (45.6%) grew despite no recombinant human growth hormone replacement therapy. At diagnosis, 12/57 (21%) patients were obese, and 33/57 (57.9%) at study evaluation, and after 3.2 years (median) post first therapy. There was no influence of height Z score on body mass index Z score. Body mass index Z score at diagnosis positively influenced body mass index Z score, total body fat, waist circumference and the presence of the metabolic syndrome post-treatment. Replacement of recombinant human growth hormone decreased total body fat and visceral adipose tissue. Craniopharyngioma patients worsened body mass index Z score category 3.2 years (median) after first treatment. Body mass index Z score increased due to real weight gain, without height decrease. Replacement of recombinant human growth hormone had beneficial effect on adiposity.

Fibroblast Growth Factor 9 Regulation by MicroRNAs Controls Lung Development and Links DICER1 Loss to the Pathogenesis of Pleuropulmonary Blastoma.

Pleuropulmonary Blastoma (PPB) is the primary neoplastic manifestation of a pediatric cancer predisposition syndrome that is associated with several diseases including cystic nephroma, Wilms tumor, neuroblastoma, rhabdomyosarcoma, medulloblastoma, and ovarian Sertoli-Leydig cell tumor. The primary pathology of PPB, epithelial cysts with stromal hyperplasia and risk for progression to a complex primitive sarcoma, is associated with familial heterozygosity and lesion-associated epithelial loss-of-heterozygosity of DICER1. It has been hypothesized that loss of heterozygosity of DICER1 in lung epithelium is a non-cell autonomous etiology of PPB and a critical pathway that regulates lung development; however, there are no known direct targets of epithelial microRNAs (miRNAs) in the lung. Fibroblast Growth Factor 9 (FGF9) is expressed in the mesothelium and epithelium during lung development and primarily functions to regulate lung mesenchyme; however, there are no known mechanisms that regulate FGF9 expression during lung development. Using mouse genetics and molecular phenotyping of human PPB tissue, we show that FGF9 is overexpressed in lung epithelium in the initial multicystic stage of Type I PPB and that in mice lacking epithelial Dicer1, or induced to overexpress epithelial Fgf9, increased Fgf9 expression results in pulmonary mesenchymal hyperplasia and a multicystic architecture that is histologically and molecularly indistinguishable from Type I PPB. We further show that miR-140 is expressed in lung epithelium, regulates epithelial Fgf9 expression, and regulates pseudoglandular stages of lung development. These studies identify an essential miRNA-FGF9 pathway for lung development and a non-cell autonomous signaling mechanism that contributes to the mesenchymal hyperplasia that is characteristic of Type I PPB.

Presence and Distribution of Scirtothrips dorsalis Hood (Thysanoptera: Thripidae) in Colombia.

The presence and distribution of Scirtothrips dorsalis was reported in Colombia in the Andean, Caribbean, and Orinoquia regions, from 0 to 1,200 meters of altitude (MASL) in the warm climate zone, with less than 2,000 mm rainfall per year and a temperature above 24°C, which corresponds to the tropical dry forest life zone (TDF). Larvae and adults of S. dorsalis were found on 13 plant species belonging to 12 genera in 12 families, of 181 plant species sampled from 129 genera in 47 families sampled. The botanical species with S. dorsalis presence included cotton (Gossypium hirsutum) L., mango (Mangifera indica) L., chili pepper (Capsicum frutescens) L., bell pepper (Capsicum annuum) L., orange (Citrus sinensis) L., jasmine orange (Murraya paniculata) L., rose (Rosa sp.), and the weeds Sesbania exaltata (Mill.), Phyllanthus niruri L., Ludwigia hyssopifolia Vahl, Euphorbia hypericifolia L., Echinochloa colona L., and Amaranthus spinosus (L.). S. dorsalis prefers young leaves and floral structures, but in cotton it was also associated with squares. The low number of host plants is evident, far from the extensive lists obtained by other authors in other latitudes. S. dorsalis invaded Colombia only in recent years, and this is the first study of the presence and distribution of this thrips in the area.

Characterization of four Latin American families confirms previous findings and reveals novel features of acid-labile subunit deficiency.

OBJECTIVE: Acid-labile subunit deficiency (ACLSD), caused by inactivating mutations in both IGFALS gene alleles, is characterized by marked reduction in IGF-I and IGFBP-3 levels associated with mild growth retardation. The aim of this study was to expand the known phenotype and genetic characteristics of ACLSD by reporting data from four index cases and their families. DESIGN: Auxological data, biochemical and genetic studies were performed in four children diagnosed with ACLSD and all available relatives. METHODS: Serum levels of IGF-I, IGFBP-3, acid-labile subunit (ALS), and in vitro ternary complex formation (ivTCF) were determined. After sequencing the IGFALS gene, pathogenicity of novel identified variants was evaluated by in vitro expression in transfected Chinese hamster ovarian (CHO) cells. ALS protein was detected in patients' sera and CHO cells conditioned media and lysates by Western immunoblot (WIB). RESULTS: Four index cases and four relatives were diagnosed with ACLSD. The following variants were found: p.Glu35Glyfs*17, p.Glu35Lysfs*87, p.Leu213Phe, p.Asn276Ser, p.Leu409Phe, p.Ala475Val and p.Ser490Trp. ACLSD patients presented low IGF-I and low or undetectable levels of IGFBP-3 and ALS. Seven out of 8 patients did not form ivTCF. CONCLUSIONS: This study confirms previous findings in ACLSD, such as the low IGF-I and a more severe reduction in IGFBP-3 levels, and a gene dosage effect observed in heterozygous carriers (HC). In addition, father-to-son transmission (father compound heterozygous and mother HC), preservation of male fertility, and marginal ALS expression with potential involvement in preserved responsiveness to rhGH treatment, are all novel aspects, not previously reported in this condition.

Visfatin is a positive predictor of bone mineral density in young survivors of acute lymphocytic leukemia.

Bone mass acquisition may be compromised in survivors of childhood acute lymphocytic leukemia due to various factors, including adiposity. Fat accumulation can affect bone through the direct effect of adipokines or indirectly through the state of chronic inflammation. The aim of this study was to evaluate the effect of body composition and adipokines on bone mass in survivors of acute lymphocytic leukemia. This was a cross-sectional study of 56 survivors aged between 15 and 24 years, 44.6 % of whom received cranial radiotherapy (18-24 Gy), assessed according to body fat, lean mass, and bone mineral density (dual energy X-ray absorptiometry), computed tomography scan-derived abdominal adipose tissue, and adipokines by a multiple regression analysis. Both lumbar spine L1-L4 (trabecular bone) and total body (cortical bone) bone mineral density were positively correlated with visfatin (p < 0.050). Lean mass index was positively correlated, while waist-to-height ratio was negatively correlated with cortical bone (p < 0.010). Low bone mineral density for chronological age was detected in 5.4 % of patients in total body, and 8.9 % at the lumbar spine. In survivors of acute lymphocytic leukemia, visfatin may play an important role in the complex relationship between body composition and bone. At present, visfatin may represent a model for further study of bone metabolism, and could possibly explain the unknown mechanisms linking bone metabolism and cancer.

Cosegregation of a novel mutation in the sixth transmembrane segment of the luteinizing/choriogonadotropin hormone receptor with two Brazilian siblings with severe testotoxicosis.

PURPOSE: Testotoxicosis is an autosomal dominant form of gonadotropin-independent precocious puberty caused by heterozygous constitutively activating mutations of the luteinizing hormone/choriogonadotropin receptor (LHCGR) gene. The aim of this study was to describe two Brazilian siblings with testotoxicosis, to confirm the molecular diagnosis, and to perform an in silico analysis of a novel mutation in the hot spot of the LHCGR gene. MATERIALS AND METHODS: Molecular analysis of the mutation on the LHCGR gene was performed by direct Sanger sequencing, followed by an in silico analysis using HOPE bioinformatics tool to predict a functional defect of the mutant. RESULTS: Both patients presented with gonadotropin-independent precocious puberty before the age of four years. Genetic analysis revealed a novel non-maternally inherited p.Asp578Val mutation of the LHCGR gene. An in silico analysis showed that the p.Asp578Val mutation disturbed amino acid physicochemical features regarding its size, charge, and hydrophobicity value. CONCLUSIONS: Clinical and hormonal profile of the siblings here evaluated was not different while compared to those patients previously described. An in silico mutation analysis reinforced the causative role of recurrent activating mutations in the intracellular loop and transmembrane helices of the LHCGR. The segregation of this mutation with the offsprings' phenotype indicated that it is causative.

International multi-site survey on the use of online support groups in bipolar disorder.

BACKGROUND: Peer support is an established component of recovery from bipolar disorder, and online support groups may offer opportunities to expand the use of peer support at the patient's convenience. Prior research in bipolar disorder has reported value from online support groups. AIMS: To understand the use of online support groups by patients with bipolar disorder as part of a larger project about information seeking. METHODS: The results are based on a one-time, paper-based anonymous survey about information seeking by patients with bipolar disorder, which was translated into 12 languages. The survey was completed between March 2014 and January 2016 and included questions on the use of online support groups. All patients were diagnosed by a psychiatrist. Analysis included descriptive statistics and general estimating equations to account for correlated data. RESULTS AND CONCLUSIONS: The survey was completed by 1222 patients in 17 countries. The patients used the Internet at a percentage similar to the general public. Of the Internet users who looked online for information about bipolar disorder, only 21.0% read or participated in support groups, chats, or forums for bipolar disorder (12.8% of the total sample). Given the benefits reported in prior research, clarification of the role of online support groups in bipolar disorder is needed. With only a minority of patients using online support groups, there are analytical challenges for future studies.

Non-Pincer-Type Manganese Complexes as Efficient Catalysts for the Hydrogenation of Esters.

Catalytic hydrogenation of carboxylic acid esters is essential for the green production of pharmaceuticals, fragrances, and fine chemicals. Herein, we report the efficient hydrogenation of esters with manganese catalysts based on simple bidentate aminophosphine ligands. Monoligated Mn PN complexes are particularly active for the conversion of esters into the corresponding alcohols at Mn concentrations as low as 0.2 mol % in the presence of sub-stoichiometric amounts of KOt Bu base.

Endothelial fibroblast growth factor receptor signaling is required for vascular remodeling following cardiac ischemia-reperfusion injury.

Fibroblast growth factor (FGF) signaling is cardioprotective in various models of myocardial infarction. FGF receptors (FGFRs) are expressed in multiple cell types in the adult heart, but the cell type-specific FGFR signaling that mediates different cardioprotective endpoints is not known. To determine the requirement for FGFR signaling in endothelium in cardiac ischemia-reperfusion injury, we conditionally inactivated the Fgfr1 and Fgfr2 genes in endothelial cells with Tie2-Cre (Tie2-Cre, Fgfr1(f/f), Fgfr2(f/f) DCKO mice). Tie2-Cre, Fgfr1(f/f), Fgfr2(f/f) DCKO mice had normal baseline cardiac morphometry, function, and vessel density. When subjected to closed-chest, regional cardiac ischemia-reperfusion injury, Tie2-Cre, Fgfr1(f/f), Fgfr2(f/f) DCKO mice showed a significantly increased hypokinetic area at 7 days, but not 1 day, after reperfusion. Tie2-Cre, Fgfr1(f/f), Fgfr2(f/f) DCKO mice also showed significantly worsened cardiac function compared with controls at 7 days but not 1 day after reperfusion. Pathophysiological analysis showed significantly decreased vessel density, increased endothelial cell apoptosis, and worsened tissue hypoxia in the peri-infarct area at 7 days following reperfusion. Notably, Tie2-Cre, Fgfr1(f/f), Fgfr2(f/f) DCKO mice showed no impairment in the cardiac hypertrophic response. These data demonstrate an essential role for FGFR1 and FGFR2 in endothelial cells for cardiac functional recovery and vascular remodeling following in vivo cardiac ischemia-reperfusion injury, without affecting the cardiac hypertrophic response. This study suggests the potential for therapeutic benefit from activation of endothelial FGFR pathways following ischemic injury to the heart.

Green and Efficient: Iron-Catalyzed Selective Oxidation of Olefins to Carbonyls with O2.

A mild and operationally simple iron-catalyzed protocol for the selective aerobic oxidation of aromatic olefins to carbonyl compounds is described. Catalyzed by a Fe(III) species bearing a pyridine bisimidazoline ligand at 1 atm of O2, α- and ß-substituted styrenes were cleaved to afford benzaldehydes and aromatic ketones generally in high yields with excellent chemoselectivity and very good functional group tolerance, including those containing radical-sensitive groups. With α-halo-substituted styrenes, the oxidation took place with concomitant halide migration to afford α-halo acetophenones. Various observations have been made, pointing to a mechanism in which both molecular oxygen and the olefinic substrate coordinate to the iron center, leading to the formation of a dioxetane intermediate, which collapses to give the carbonyl product.

Conformational features of secondary N-cyclopropyl amides.

NMR studies in conjunction with ab initio calculations revealed unexpected conformational behavior of N-cyclopropylacetamide (1). This secondary amide displays 16-19% E-rotamer (cis) around the carbonyl-nitrogen bond in apolar solvents, in contrast to other aliphatic secondary acetamides in which significant E-rotamer populations are rare due to steric contacts between the substituents on the amide bond. In addition, 1 adopts an ortho conformation around the N-cPr bond instead of the anti conformation generally preferred by secondary acetamides. This distinct conformational behavior was also observed for other secondary N-cyclopropyl amides.

Regioselective acceptorless dehydrogenative coupling of N-heterocycles toward functionalized quinolines, phenanthrolines, and indoles.

A new strategy has been developed for the oxidant- and base-free dehydrogenative coupling of N-heterocycles at mild conditions. Under the action of an iridium catalyst, N-heterocycles undergo multiple sp(3) CH activation steps, generating a nucleophilic enamine that reacts in situ with various electrophiles to give highly functionalized products. The dehydrogenative coupling can be cascaded with Friedel-Crafts addition, resulting in a double functionalization of the N-heterocycles.

Dehydrogenative α-oxygenation of ethers with an iron catalyst.

Selective α-oxidation of ethers under aerobic conditions is a long-pursued transformation; however, a green and efficient catalytic version of this reaction remains challenging. Herein, we report a new family of iron catalysts capable of promoting chemoselective α-oxidation of a range of ethers with excellent mass balance and high turnover numbers under 1 atm of O2 with no need for any additives. Unlike metalloenzymes and related biomimetics, the catalyst produces H2 as the only byproduct. Mechanistic investigations provide evidence for an unexpected two-step reaction pathway, which involves dehydrogenative incorporation of O2 into the ether to give a peroxobisether intermediate followed by cleavage of the peroxy bond to form two ester molecules, releasing stoichiometric H2 gas in each step. The operational simplicity and environmental friendliness of this methodology affords a useful alternative for performing oxidation, while the unique ability of the catalyst in oxygenating a substrate via dehydrogenation points to a new direction for understanding metalloenzymes and designing new biomimetic catalysts.

Rationale, Design, and Patient Characteristics of a Cluster-Randomized Pragmatic Trial to Improve Mineralocorticoid Antagonist Use.

BACKGROUND: Despite robust evidence and strong guideline recommendations supporting use of mineralocorticoid receptor antagonists (MRAs) to improve outcomes in patients with heart failure with reduced ejection fraction (HFrEF), these medications remain underused in clinical practice. OBJECTIVES: The goal is to determine if providing a tailored best practice alert (BPA) to outpatient providers suggesting guideline-recommended MRAs or information about available hyperkalemia treatment, if present, for patients with HFrEF will increase short-term MRA prescriptions. METHODS: PROMPT-MRA (Pragmatic Trial of Messaging to Providers About Treatment With Mineralocorticoid Receptor Antagonists) is a pragmatic, cluster-randomized, controlled study. A total of 119 providers were randomized to receive a BPA or usual care. During an outpatient visit with participating providers, the BPA displayed recent laboratory test values and ejection fraction. The alert suggested guideline-recommended MRAs for eligible patients with a serum potassium of <5.0 mEq/L or novel potassium binders for those with a serum potassium of ≥5.0 mEq/L, each linked to an order set containing the corresponding medication and laboratory monitoring. RESULTS: PROMPT-MRA completed enrollment with 1,210 patients. The primary outcome of PROMPT-MRA is to determine if a tailored BPA for outpatients with HFrEF will lead to higher MRA prescriptions 6 months following randomization compared with usual care. Secondary outcomes included incidence of hyperkalemia, use of novel potassium binders, heart failure hospitalizations, and mortality. CONCLUSIONS: If effective, the BPA can be scaled to improve population health outcomes with increased MRA prescribing among eligible patients with HFrEF, with or without a history of hyperkalemia. (Pragmatic Trial of Alerts for Use of Mineralocorticoid Receptor Antagonists [PROMPT-MRA]; NCT04903717).

Impact of Digital Health Technology on Quality of Life in Patients With Heart Failure.

BACKGROUND: Digital health tools may improve quality of life (QoL) in patients with heart failure (HF) by promoting self-care, knowledge, and engagement. OBJECTIVES: This study evaluates the effect of 3 digital technologies on QoL in patients with HF. METHODS: A total of 182 patients were randomized to usual care or one of the technologies promoting self-care: Bodyport (cardiac scale), Conversa (conversational platform), or Noom (smartphone application). The primary outcome was 90-day change in QoL, as assessed by the Kansas City Cardiomyopathy Questionnaire (KCCQ) Overall Summary Score (OSS). RESULTS: A total of 151 participants (83%) completed their 90-day surveys. The median age of enrolled participants was 61 years (IQR: 53-69 years), and 37.9% were women. No group had any significant change in KCCQ OSS or improvement relative to usual care. However, symptoms and physical function at 90 days, as assessed by the Total Symptom Score (TSS) and Clinical Summary Score (CSS), were significantly improved in the Noom group relative to usual care: TSS median change of +4.2 points (IQR -1 to +16.7) vs -1 points (IQR: -13.5 to +7.8; P = 0.006); CSS median change of +2.8 points (IQR: -1 to +14.6) vs -3.1 points (IQR: -10.2 to +3; P = 0.002). CONCLUSIONS: Three digital interventions showed no independent effect on QoL as assessed by the KCCQ OSS. However, participants randomized to the Noom technology demonstrated improved KCCQ TSS and CSS relative to usual care. Although digital tools may be an important component of longitudinal care for patients with HF, larger studies are needed to better understand their effectiveness and optimal deployment. (Evaluating Efficacy of Digital Health Technology in the Treatment of Congestive Heart Failure; NCT04394754).

Wearables in Cardiovascular Disease.

Wearable devices stand to revolutionize the way healthcare is delivered. From consumer devices that provide general health information and screen for medical conditions to medical-grade devices that allow collection of larger datasets that include multiple modalities, wearables have a myriad of potential uses, especially in cardiovascular disorders. In this review, we summarize the underlying technologies employed in these devices and discuss the regulatory and economic aspects of such devices as well as the future implications of their use.