What have we learned from the real-world efficacy of FFA in DS and LGS? A post-marketing study in clinical practice.

OBJECTIVE: To evaluate the effectiveness and tolerability of fenfluramine (FFA) in routine clinical practice treating real-world populations with Dravet syndrome (DS) and Lennox-Gastaut syndrome (LGS). METHODS: This was a retrospective analysis of patients with DS or LGS who initiated FFA treatment from 2018 to 2022 at a single center. Patient demographics, medical history, seizure characteristics, and treatment outcomes were collected from electronic medical records. Duration of FFA treatment, dosage regimens, seizure frequency, seizure severity, improvements in cognitive, social, and motor outcomes, and adverse events were extracted and analyzed. Effectiveness was assessed using ≥50 % sustained reduction in monthly seizure frequency vs baseline for ≥2 consecutive months at 12 months; seizure freedom was a secondary measure. RESULTS: Seizure frequency data was available for 56 of 68 patients included in the study. At 12 months, 50 patients (89.3 %) remained on FFA treatment; 58 % of these patients achieved a ≥50 % sustained response and 10 % experienced seizure freedom. Cognitive, motor, and social improvement were noted in 70.7 %, 36.2 %, and 27.6 % of patients, respectively. The total number of concomitant antiseizure medications was reduced by ≥1 in 29.4 % of patients. No differences were found between DS and LGS patients in these outcomes; age at start of FFA and age at the 12-month timepoint did not have an effect. At least one AE was experienced by 59.7% of patients; in 86.5% of the cases, AEs were plausibly related to treatment. While 70.3% of AEs were self-resolving and 81.8% of the remaining patients experienced mild AEs, 1 patient experienced a serious AE unrelated to FFA which resulted in the patient's death. There were no cases of pulmonary arterial hypertension or ventricular heart disease. SIGNIFICANCE: The effectiveness and tolerability of FFA treatment in patients with DS or LGS in this retrospective analysis of real-world data were consistent with those seen in randomized clinical trials.

Ultrasound-Based Recovery of Anti-Inflammatory and Antimicrobial Extracts of the Acidophilic Microalga Coccomyxa onubensis.

In the present study, the recovery of valuable molecules of proven anti-inflammatory and antimicrobial activity of the acidophilic microalga Coccomyxa onubensis (C. onubensis) were evaluated using green technologies based on ultrasound-assisted extraction (UAE). Using a factorial design (3 × 2) based on response surface methodology and Pareto charts, two types of ultrasonic equipment (bath and probe) were evaluated to recover valuable compounds, including the major terpenoid of C. onubensis, lutein, and the antimicrobial activity of the microalgal extracts obtained under optimal ultrasound conditions (desirability function) was evaluated versus conventional extraction. Significant differences in lutein recovery were observed between ultrasonic bath and ultrasonic probe and conventional extraction. Furthermore, the antimicrobial activity displayed by C. onubensis UAE-based extracts was greater than that obtained in solvent-based extracts, highlighting the effects of the extracts against pathogens such as Enterococcus hirae and Bacillus subtilis, followed by Staphylococcus aureus and Escherichia coli. In addition, gas chromatography-mass spectrometry was performed to detect valuable anti-inflammatory and antimicrobial biomolecules present in the optimal C. onubensis extracts, which revealed that phytol, sterol-like, terpenoid, and even fatty acid structures could also be responsible for the antibacterial activities of the extracts. Moreover, UAE displayed a positive effect on the recovery of valuable molecules, improving biocidal effects. Our study results facilitate the use of green technology as a good tool in algal bioprocess engineering, improving energy consumption and minimizing environmental impacts and process costs, as well as provide a valuable product for applications in the field of biotechnology.

Cross-site reproducibility of human cortical organoids reveals consistent cell type composition and architecture.

Background: Reproducibility of human cortical organoid (hCO) phenotypes remains a concern for modeling neurodevelopmental disorders. While guided hCO protocols reproducibly generate cortical cell types in multiple cell lines at one site, variability across sites using a harmonized protocol has not yet been evaluated. We present an hCO cross-site reproducibility study examining multiple phenotypes. Methods: Three independent research groups generated hCOs from one induced pluripotent stem cell (iPSC) line using a harmonized miniaturized spinning bioreactor protocol. scRNA-seq, 3D fluorescent imaging, phase contrast imaging, qPCR, and flow cytometry were used to characterize the 3 month differentiations across sites. Results: In all sites, hCOs were mostly cortical progenitor and neuronal cell types in reproducible proportions with moderate to high fidelity to the in vivo brain that were consistently organized in cortical wall-like buds. Cross-site differences were detected in hCO size and morphology. Differential gene expression showed differences in metabolism and cellular stress across sites. Although iPSC culture conditions were consistent and iPSCs remained undifferentiated, primed stem cell marker expression prior to differentiation correlated with cell type proportions in hCOs. Conclusions: We identified hCO phenotypes that are reproducible across sites using a harmonized differentiation protocol. Previously described limitations of hCO models were also reproduced including off-target differentiations, necrotic cores, and cellular stress. Improving our understanding of how stem cell states influence early hCO cell types may increase reliability of hCO differentiations. Cross-site reproducibility of hCO cell type proportions and organization lays the foundation for future collaborative prospective meta-analytic studies modeling neurodevelopmental disorders in hCOs.

Modulation of tau tubulin kinases (TTBK1 and TTBK2) impacts ciliogenesis.

Tau tubulin kinase 1 and 2 (TTBK1/2) are highly homologous kinases that are expressed and mediate disease-relevant pathways predominantly in the brain. Distinct roles for TTBK1 and TTBK2 have been delineated. While efforts have been devoted to characterizing the impact of TTBK1 inhibition in diseases like Alzheimer's disease and amyotrophic lateral sclerosis, TTBK2 inhibition has been less explored. TTBK2 serves a critical function during cilia assembly. Given the biological importance of these kinases, we designed a targeted library from which we identified several chemical tools that engage TTBK1 and TTBK2 in cells and inhibit their downstream signaling. Indolyl pyrimidinamine 10 significantly reduced the expression of primary cilia on the surface of human induced pluripotent stem cells (iPSCs). Furthermore, analog 10 phenocopies TTBK2 knockout in iPSCs, confirming a role for TTBK2 in ciliogenesis.

Long-term trajectories of non-native vegetation on islands globally.

Human-mediated changes in island vegetation are, among others, largely caused by the introduction and establishment of non-native species. However, data on past changes in non-native plant species abundance that predate historical documentation and censuses are scarce. Islands are among the few places where we can track human arrival in natural systems allowing us to reveal changes in vegetation dynamics with the arrival of non-native species. We matched fossil pollen data with botanical status information (native, non-native), and quantified the timing, trajectories and magnitude of non-native plant vegetational change on 29 islands over the past 5000 years. We recorded a proportional increase in pollen of non-native plant taxa within the last 1000 years. Individual island trajectories are context-dependent and linked to island settlement histories. Our data show that non-native plant introductions have a longer and more dynamic history than is generally recognized, with critical implications for biodiversity baselines and invasion biology.

Anthropogenic transitions from forested to human-dominated landscapes in southern Macaronesia.

The extinction of iconic species such as the dodo and the deforestation of Easter Island are emblematic of the transformative impact of human colonization of many oceanic islands, especially those in the tropics and subtropics. Yet, the interaction of prehistoric and colonial-era colonists with the forests and forest resources they encountered can be complex, varies between islands, and remains poorly understood. Long-term ecological records (e.g., fossil pollen) provide the means to understand these human impacts in relation to natural change and variability pre- and postcolonization. Here we analyze paleoecological archives in forested landscapes of the Canary Islands and Cabo Verde, first colonized approximately 2,400 to 2,000 and 490 y ago, respectively. We demonstrate sensitivity to regional climate change prior to human colonization, followed by divergent but gradual impacts of early human settlement. These contrast with more rapid transformation in the colonial era, associated with significant increases in anthropogenic pressures. In the Canary Islands, at least two native tree taxa became extinct and lowland thermophilous woodlands were largely converted to agricultural land, yet relictual subtropical laurel forests persisted with limited incursion of nonnative species. In Cabo Verde, in contrast, thermophilous woodlands were depleted and substituted by open landscapes and introduced woodlands. Differences between these two archipelagos reflect the changing cultural practices and societal interactions with forests and illustrate the importance of long-term data series in understanding the human footprint on island ecosystems, information that will be critically important for current and future forest restoration and conservation management practices in these two biodiversity hotspots.

Pathogenic SPTBN1 variants cause an autosomal dominant neurodevelopmental syndrome.

SPTBN1 encodes ßII-spectrin, the ubiquitously expressed ß-spectrin that forms micrometer-scale networks associated with plasma membranes. Mice deficient in neuronal ßII-spectrin have defects in cortical organization, developmental delay and behavioral deficiencies. These phenotypes, while less severe, are observed in haploinsufficient animals, suggesting that individuals carrying heterozygous SPTBN1 variants may also show measurable compromise of neural development and function. Here we identify heterozygous SPTBN1 variants in 29 individuals with developmental, language and motor delays; mild to severe intellectual disability; autistic features; seizures; behavioral and movement abnormalities; hypotonia; and variable dysmorphic facial features. We show that these SPTBN1 variants lead to effects that affect ßII-spectrin stability, disrupt binding to key molecular partners, and disturb cytoskeleton organization and dynamics. Our studies define SPTBN1 variants as the genetic basis of a neurodevelopmental syndrome, expand the set of spectrinopathies affecting the brain and underscore the critical role of ßII-spectrin in the central nervous system.

Generation of an induced pluripotent stem cell line (UNCCi002-A) from a healthy donor using a non-integration system to study Cerebral Cavernous Malformation (CCM).

The generation of induced pluripotent stem cells (iPSCs) from healthy individuals is an invaluable resource as reference control in disease modeling and drug discovery. This paper details the reprogramming of peripheral blood mononuclear cells (PBMCs) isolated from a healthy 27 years-old male using non-integration technology. The derived iPSCs displayed typical pluripotent stem cell morphology, the capacity to differentiate into the three germ layers, and normal karyotype. This iPSC line will be used as a reference control to study the Cerebral Cavernous Malformation disease mechanism.

Segmentor: a tool for manual refinement of 3D microscopy annotations.

BACKGROUND: Recent advances in tissue clearing techniques, combined with high-speed image acquisition through light sheet microscopy, enable rapid three-dimensional (3D) imaging of biological specimens, such as whole mouse brains, in a matter of hours. Quantitative analysis of such 3D images can help us understand how changes in brain structure lead to differences in behavior or cognition, but distinguishing densely packed features of interest, such as nuclei, from background can be challenging. Recent deep learning-based nuclear segmentation algorithms show great promise for automated segmentation, but require large numbers of accurate manually labeled nuclei as training data. RESULTS: We present Segmentor, an open-source tool for reliable, efficient, and user-friendly manual annotation and refinement of objects (e.g., nuclei) within 3D light sheet microscopy images. Segmentor employs a hybrid 2D-3D approach for visualizing and segmenting objects and contains features for automatic region splitting, designed specifically for streamlining the process of 3D segmentation of nuclei. We show that editing simultaneously in 2D and 3D using Segmentor significantly decreases time spent on manual annotations without affecting accuracy as compared to editing the same set of images with only 2D capabilities. CONCLUSIONS: Segmentor is a tool for increased efficiency of manual annotation and refinement of 3D objects that can be used to train deep learning segmentation algorithms, and is available at https://www.nucleininja.org/ and https://github.com/RENCI/Segmentor .

The human dimension of biodiversity changes on islands.

Islands are among the last regions on Earth settled and transformed by human activities, and they provide replicated model systems for analysis of how people affect ecological functions. By analyzing 27 representative fossil pollen sequences encompassing the past 5000 years from islands globally, we quantified the rates of vegetation compositional change before and after human arrival. After human arrival, rates of turnover accelerate by a median factor of 11, with faster rates on islands colonized in the past 1500 years than for those colonized earlier. This global anthropogenic acceleration in turnover suggests that islands are on trajectories of continuing change. Strategies for biodiversity conservation and ecosystem restoration must acknowledge the long duration of human impacts and the degree to which ecological changes today differ from prehuman dynamics.

Generation of an integration-free induced pluripotent stem cell line (UNC001-A) from blood of a healthy individual.

Induced pluripotent stem cells (iPSCs) generated from young, healthy individuals are valuable tools for investigating molecular disease mechanisms during the early development of the brain vasculature. We generated an iPSC line from peripheral blood mononuclear cells (PBMCs) isolated from a healthy 13-yeard old female donor using the Sendai virus. The iPSCs differentiated into endothelial cells, astrocytes, and neurons. This iPSC line can serve as a healthy reference control for comparative studies in drug development and modeling the early onset of Cerebral Cavernous Malformation (CCM).

Dinuclear Cu(I) Halides with Terphenyl Phosphines: Synthesis, Photophysical Studies, and Catalytic Applications in CuAAC Reactions.

Several dinuclear terphenyl phosphine copper(I) halide complexes of composition [CuX(PR2Ar')]2 (X = Cl, Br, I; R = hydrocarbyl, Ar' = 2,6-diarylterphenyl radical), 1-5, have been isolated from the reaction of CuX with 1 equiv of the phosphine ligand. Most of them have been characterized by X-ray diffraction studies in the solid state, thus allowing comparative discussions of different structural parameters, namely, Cu···Cu and Cu···Aryl separations, conformations adopted by coordinated phosphines, and planarity of the Cu2X2 cores. Centrosymmetric complexes [CuI(PMe2ArXyl2)]2, 1c, and [CuI(PEt2ArMes2)]2, 3c, despite their similar structures, show very distinct photoluminescence (PL) in powder form at room temperature. The photophysical behavior of these compounds in liquid solution, solid-solid Zeonex solution and powder samples at room temperature and 77 K have been investigated and supported by DFT calculation. Identification of vibronic coupling modes, done by group theory calculations and the technique of projection operators, shows that the manifestation of these modes is conditioned by crystal packing. Complexes [CuI(PMe2ArXyl2)]2, 1c, and [CuI(PEt2ArMes2)]2, 3c, display remarkable activity in copper-catalyzed azide-alkyne cycloaddition reactions involving preformed and in situ-made azides. Reactions are performed in H2O, under aerobic conditions, with low catalyst loadings and tolerate the use of iodoalkynes as substrates.

Derivation of Induced Pluripotent Stem Cells from Human Fibroblasts Using a Non-integrative System in Feeder-free Conditions.

Induced pluripotent stem cells (iPSCs) are genetically reprogrammed somatic cells that exhibit features identical to those of embryonic stem cells (ESCs). Multiple approaches are available to derive iPSCs, among which the Sendai virus is the most effective at reprogramming different cell types. Here we describe a rapid, efficient, safe, and reliable approach to reprogram human fibroblasts into iPSCs that are compatible with future iPSCs uses such as genome editing and differentiation to a transplantable cell type.

Trispyrazolylborate Ligands Supported on Vinyl Addition Polynorbornenes and Their Copper Derivatives as Recyclable Catalysts.

Polynorbornenes prepared by vinyl addition polymerization and bearing pendant alkenyl groups serve as skeletons to support trispyrazolylborate ligands (Tpx ) built at those alkenyl sites. Reaction with CuI in acetonitrile led to VA-PNB-Tpx Cu(NCMe) (VA-PBN=vinyl addition polynorbornene) with a 0.8-1.4 mmol incorporation of Cu per gram of polymer. The presence of tetracoordinated copper(I) ions was been assessed by FTIR studies on the corresponding VA-PNB-Tpx Cu(CO) adducts, in agreement with those on discrete Tpx Cu(CO). The new materials were employed as heterogeneous catalysts in several carbene- and nitrene-transfer reactions, showing a behavior similar to that of the homogeneous counterparts but also being recycled several times maintaining a high degree of activity and selectivity. This is the first example of supported Tpx ligands onto polymeric supports with catalytic applications.

Left ventricular functional parameters by gated SPECT myocardial perfusion imaging in a Latin American country.

BACKGROUND: There is paucity of data on left ventricular (LV) functional parameters using gated SPECT myocardial perfusion imaging (MPI) from the Latin American region. This study provides detailed information in low-risk patients both at rest and during exercise. METHODS AND RESULTS: We studied 90 patients (50 men) with a very low likelihood of coronary artery disease. Gated-SPECT MPI was performed with Tc-99m MIBI using a 2-day protocol, with 16 frames/R-R cycle. The LV ejection fraction and volumes were not different between the rest and post-stress images. LVEF was 68 ± 7% post-stress and 70 ± 7% at rest in women, and 62 ± 7% and 63 ± 7%, respectively, in men (P = .19, .26). LV volumes were larger in men than women (P < .01). There were no differences in most variables obtained at rest or post-stress. Transient ischemic dilatation was similar, with upper limits of 1.20 and 1.19 in women and men, respectively (P = NS). CONCLUSIONS: These data could prove helpful for the interpretation of gated SPECT MPI data in Latin America using identical protocol as used in this study.

Reclasificación de la severidad de la estenosis aórtica con la utilización del enfoque paraesternal derecho con transductor ciego / Reclassification of the severity of aortic stenosis obtaining gradients from right parasternal view with Pedof transducer

La severidad de la estenosis aórtica (EA) es uno de los pilares que decide la sustitución valvular. El ecocardiograma Doppler (ED) es de elección para el diagnóstico y cuantificación mediante la determinación de la velocidad máxima (VMáx), gradiente medio (GM) y área valvular (AV). VMáx y GM se obtienen desde múltiples enfoques, pero la utilización del enfoque paraesternal derecho (PED) es poco frecuente. Objetivo: determinar la magnitud de la reclasificación de la EA con la utilización del enfoque PED con transductor ciego. Método: se estudian prospectivamente pacientes con EA moderada o severa por ED desde cualquier enfoque. Se considera EA moderada: VMáx 3 a 3,9 m/s, GM 20 a 39 mmHg o AV 1,1 a 1,5 cm2. EA severa: VMáx ³4 m/s, GM ³40 mmHg o AV ?1 cm2. Criterios de exclusión: fracción de eyección de ventrículo izquierdo (FEVI) <50%, insuficiencia valvular aórtica o mitral ³ moderada, hemoglobina (Hb) <11 g/dl. Se utilizan enfoques apical (ÁPEX), PED y subxifoideo con transductores convencional y ciego. Resultado: se incluyen 100 pacientes de 74,0 ±12 años, sexo femenino 49%, FEVI 69,1±8,4%. Por ÁPEX EA severa 56% y no severa 44%. Enfoque con gradiente más alto: ÁPEX 33/100, PED 48/100, más de un enfoque 19/100; las EA moderadas por ÁPEX son severas por PED: 18/33 (54,6%, IC 95% 36,4-71,9); leves por ÁPEX son severas por PED: 3/11 (27,3% IC 95% 6,0-61,0). PED reclasifica como severas 21 de las 44 consideradas moderadas o leves por ÁPEX (47,7% IC 95% 32,5-63,3). Conclusión: el enfoque PED obtiene los valores de gradiente más altos en 48% de los casos. En EA no severa por ÁPEX, el PED reclasifica como severa una de cada dos.

The severity of aortic stenosis (AS) is one of the main issues for the decision of valve replacement. Doppler echocardiography (DE) is the modality of choice for diagnosis and quantification by maximum velocity (MV), medium gradient (MG), and valve area (VA). MV and MG can be obtained from multiple views, but the use of right parasternal (RPS) view is not frequent. Objective: to know the magnitude of reclassification of AS with the use of right parasternal view with blind transducer. Method: patients with moderate or severe AS from any view by DE are prospectively studied. Moderate AS is considered with MV 3-3.9 m/s, MG 20-39 mmHg or VA 1.1-1.5 cm2. Severe AS: MV ³ 4 m/s, MG ³ 40 mm Hg or VA ? 1 cm2. Exclusion criteria: left ventricular ejection fraction (LVEF)<50%, ³ moderate aortic or mitral valve regurgitation, hemoglobin < 11 g/dl. Apical (ÁPEX), right para-sternal (RPS) and subxyfoid views are used with conventional and Pedof transducers. Results: We included 100 patients with age 74.0±12 years, 49% women, LVEF 69.1±8.4%. View with highest gradient: apex 33/100, RPS 48/100, more than one view 19/100; moderate by apex and severe by RPS: 18/33 (54,6%, IC 95% 36,4-71,9; mild by APEX and severe by RPS 3/11 (27.3% IC 95% 6.0-61.0). RPS reclassifies as severe 21 of the 44 evaluated as moderate or mild by ÁPEX (47.7% IC95% 32.5-63.3). Conclusion: RPS obtains the highest gradients in 48% of patients. In non-severe AS by apical, RPS reclassifies as severe one out of two.

Catalytic Nitrene Transfer To Alkynes: A Novel and Versatile Route for the Synthesis of Sulfinamides and Isothiazoles.

A novel transformation is reported for the reaction of terminal or internal alkynes with the nitrene precursor PhI=NTs (Ts=p-toluenesulfonyl) in the presence of catalytic amounts of TpBr3 Cu(NCMe) (TpBr3 =hydrotris(3,4,5-tribromo-pyrazolylborate). Two products containing an imine functionality have been isolated from the reaction mixtures, identified as sulfinamides and isothiazoles. The former correspond to the formal reduction of the sulfone group into sulfoxide, whereas the latter involves the insertion of an alkyne carbon atom into the aromatic ring of the N-tosyl moiety.

Cambios reversibles de alteraciones basales de la contractilidad parietal del ventrículo izquierdo con drogas antiisquémicas: Estudio ecocardiográfico / Reversible changes in left ventricular resting wall-motion contractile abnormalities with anti-ischemic drugs: An echocardiographic study

Objetivos: determinar la utilidad clínica de la detección ecocardiográfica de alteraciones parietales basales de la contractilidad (ABC) reversibles con drogas antiisquémicas en pacientes con cardiopatía isquémica (CI) estable sospechada o conocida. Antecedentes: no hay referencias en la literatura al respecto. Población y método: estudio prospectivo observacional de la práctica clínica corriente en 93 pacientes ambulatorios, consecutivos (52,7% hombres, mediana 69,7 años), con indicación de ecoestrés mostrando ABC no cicatrizales. En su lugar se aplicó un protocolo con nitritos y metoprolol. Se consignaron los cambios del score segmentario (SS), del ángor y del electrocardiograma (ECG). Los pacientes fueron derivados directamente a cateterismo (n=9), internación (n=34) o domicilio (n=50). Se realizó un seguimiento a largo plazo (3,25 años-personas). Resultados: los cambios del SS, ángor y ECG fueron significativos (p < 0,001). La mortalidad global fue 6,34 p-mes-1 x 1000, con tratamiento médico versus invasivo: 8,59 vs 3,8 p-mes-1 x 1000, cateterismo directo vs internados con cateterismo diferido: 3,93 vs 7,22 p-mes-1 x 1000, internados sin cateterismo: 18,62 p-mes-1 x 1000 y domiciliarios con y sin cateterismo: 4,03 vs 4,05 p-mes-1 x 1000, respectivamente. Los pacientes con cateterismo presentaron lesiones severas mayormente de múltiples vasos. Conclusiones: la detección ecocardiográfica de ABC reversibles con drogas antiisquémicas en pacientes con CI evoca la presencia de isquemia miocárdica de reposo en una población de alto riesgo y tiene un importante valor pronóstico.

Objectives: to determine the clinical usefulness in detecting reversible resting echocardiographic segmental wall motion contractile abnormalities (ABC) in patients with stable coronary artery disease (CI). Background: There are no references in the literature. Population and method: This is a current clinical practice prospective observational study on 93 consecutive patients (58% men, median 69,7 years) with stress echocardiograms requested and showing non scarring ABC who were submitted to echocardiograms with nitrates and metoprolol instead. Left ventricular segmental wall motion score index (SS), electrocardiographic abnormalities (ECG) and chest pain changes were determined. Patients were referred either to direct catheterization (n=9), hospitalization (n=34) or to their residences (n=50). A 3,25-years-persons follow-up was performed. Results: SS, ECG abnormalities and chest pain changed significantly (p<0,001). The higher SS, the higher mortality. Global mortality was 6,34 p-mes-1 x 1000; patients with medical vs. invasive treatment: 8,59 vs 3,8 p-mes-1 x 1000, with direct catheterization vs. those hospitalized with deferred catheterization: 3,93 vs 7,22 p-mes-1 x 1000, patients hospitalized without catheterization: 18,62 p-mes-1 x 1000, and domiciliary patients with and without catheterization: 4,03 vs 4,05 p-mes-1 x 1000. Patients with catheterization showed severe multi-vessel disease mainly. Conclusions: Reversible echocardiographic ABC with anti-ischemic drugs evokes resting myocardial ischemia, a high risk CI population and has important prognostic value.

Good Sleep Health in Urban Children With Asthma: A Risk and Resilience Approach.

OBJECTIVES: To identify children demonstrating "good" sleep health in a sample of urban children with persistent asthma; to compare sociocontextual, asthma clinical characteristics, and sleep behaviors in children with "good" versus "poor" sleep health; and to examine protective effects of family-based health behaviors on sleep health. METHODS: Participants were 249 Black (33%), Latino (51%) and non-Latino White (16%) children with asthma, ages 7-9 years, and their primary caregivers. RESULTS: 32 percent of children had "good" sleep health. Well-controlled asthma and better lung function were more likely in this group. In the context of urban risks, sleep hygiene appeared to be a protective factor associated with better sleep quality. The protective effect of asthma management functioned differently by ethnic group. CONCLUSIONS: This study identifies protective processes that may guard against urban risks to optimize sleep health in children with asthma. Intervention programs can be tailored to consider specific supports that enhance sleep health in this high-risk group.

A fully recyclable heterogenized Cu catalyst for the general carbene transfer reaction in batch and flow.

A polystyrene-linked tris(triazolyl)methanecopper(i) cationic catalyst operates under heterogeneous conditions for the reaction of ethyl diazoacetate (EDA) with an array of substrates. Carbon-hydrogen as well as X-H (X = O, N) functionalization derived from the formal transfer of the carbene moiety (:CHCO2Et) from the copper center and subsequent insertion have been achieved, the reactions permitting repeated catalyst recycling and reuse. The addition of the same carbene unit to benzene leading to a cycloheptatriene derivative (Büchner reaction) or to phenylacetylene (cyclopropenation) took place at similar rates to the insertion processes and with the same catalyst recyclability. The use of this heterogenized cationic Cu catalyst in continuous flow has also been implemented. Key characteristics of the flow process are its high and constant turnover frequency (TOF) (residence times of 1 min still lead to full conversion in the reaction with ethanol after 48 h operation) and its suitability for the sequential performance of different types of carbene transfer reactions with a simple and affordable experimental setup.