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Objective Psychosocial interventions targeting glycemic health in youth with type 1 diabetes (T1D) have been promising. Nonetheless, disparities in T1D treatment and outcomes are pervasive among racially/ethnically minoritized (REM) youth and a systematic review examining the inclusion of REM youth in psychosocial interventions is lacking. Therefore, the present systematic review examined the literature to determine the inclusion of REM youth with T1D in psychosocial interventions. Methods A systematic literature review was conducted per PRISMA guidelines for psychosocial intervention studies of youth ( Results Twenty-four studies met inclusion criteria with a total of 3,117 participants. Studies utilized various psychological interventions (e.g., CBT, MI, behavioral modalities). Seventeen studies reported participants’ race/ethnicity and eleven studies included >20% REM youth. Conclusions One study examined the impact of interventions on REM youth or whether the intervention reduces existing racial/ethnic disparities. Implications for future research and practice are discussed.

Los ambientes semiáridos son dominados por condiciones extremas que influyen de manera directa en la dispersión y germinación de semillas, así como el establecimiento, desarrollo y mantenimiento de la cubierta vegetal. Este ciclo depende directamente de la disponibilidad del recurso hídrico. Sin embargo, en las zonas semiáridas el agua es limitada, por lo que las especies que ahí habitan presentan adaptaciones para su dispersión como el desarrollo de estructuras y estrategias de movilidad para asegurar su supervivencia. Las etapas de la dispersión hasta el establecimiento de las semillas se manifiestan mediante distintas estrategias o mecanismos para pasar de una fase a otra. Lo anterior aunado a la humedad, la disponibilidad de agua y los sustratos favorecen la dispersión. La interacción de los bancos de semillas y sus estructuras constituyen un factor decisivo para que las especies se adapten a las zonas áridas y semiáridas. Adicionalmente, las microestructuras seminales juegan un papel particular en cada especie al proporcionar ventajas ante las inclemencias que deben sortear, como sucede con el hilo prominente y los tegumentos delgados de las semillas, así como las formas singulares que facilitan no sólo la absorción de agua, sino la dispersión hacia sitios seguros que hagan posible iniciar el proceso de establecimiento.

Biofilm formation on an implant surface is most commonly caused by the human pathogenic bacteria Staphylococcus aureus, which can lead to implant related infections and failure. It is a major problem for both implantable orthopedic and maxillofacial devices. The current antibiotic treatments are typically delivered orally or in an injectable form. They are not highly effective in preventing or removing biofilms, and they increase the risk of antibiotic resistance of bacteria and have a dose-dependent negative biological effect on human cells. Our aim was to improve current treatments via a localized and controlled antibiotic delivery-based implant coating system to deliver the antibiotic, gentamicin (Gm). The coating contains coral skeleton derived hydroxyapatite powders (HAp) that act as antibiotic carrier particles and have a biodegradable poly-lactic acid (PLA) thin film matrix. The system is designed to prevent implant related infections while avoiding the deleterious effects of high concentration antibiotics in implants on local cells including primary human adipose derived stem cells (ADSCs). Testing undertaken in this study measured the rate of S. aureus biofilm formation and determined the growth rate and proliferation of ADSCs. After 24 h, S. aureus biofilm formation and the percentage of live cells found on the surfaces of all 5%-30% (w/w) PLA-Gm-(HAp-Gm) coated Ti6Al4V implants was lower than the control samples. Furthermore, Ti6Al4V implants coated with up to 10% (w/w) PLA-Gm-(HAp-Gm) did not have noticeable Gm related adverse effect on ADSCs, as assessed by morphological and surface attachment analyses. These results support the use and application of the antibacterial PLA-Gm-(HAp-Gm) thin film coating design for implants, as an antibiotic release control mechanism to prevent implant-related infections.

We investigate the impact of environment on the internal mass distribution of galaxies using the Middle Ages Galaxy Properties with Integral field spectroscopy (MAGPI) survey. We use 2D resolved stellar kinematics to construct Jeans dynamical models for galaxies at mean redshift $z \sim 0.3$, corresponding to a lookback time of $3-4$ Gyr. The internal mass distribution for each galaxy is parameterised by the combined mass density slope $\gamma$ (baryons $+$ dark matter), which is the logarithmic change of density with radius. We use a MAGPI sample of 28 galaxies from low-to-mid density environments and compare to density slopes derived from galaxies in the high density Frontier Fields clusters in the redshift range $0.29, Comment: Accepted for publication in MNRAS

Objective and Design: The adhesion and subsequent activation of T cells is a critical step in local inflammatory responses, particularly of alloreactive leukocytes in rejection of transplanted donor tissue. IFNγ is an adaptive cytokine that promotes endothelial cell expression of pro-adhesive factors and costimulatory molecules. We recently reported that IFNγ-induced endothelial cell antigen presenting capacity was protracted after cytokine withdrawal. This study sought to determine what intracellular signaling mediates this chronic endothelial activation by IFNγ. Approach: The durability of interferon signaling in human aortic endothelial activation was tested. Pro-adhesive and costimulatory gene expression, phenotype, secretome and JAK/STAT phosphorylation in human primary endothelial cells were measured under chronic and transient IFNγ stimulation, with various JAK inhibitors. IFNγ reporter cells were tested for STAT1 transcriptional activity with JAK inhibition and SOCS overexpression, under continuous and priming conditions. Results: Short exposure to IFNγ caused sustained elevation of adhesion molecules and chemokines up to 48hr later. JAK/STAT and interferon response factor expression were durable, dependent on new transcription but autonomous of IFNγ. Persistent STAT transcription and JAK signaling in the endothelium was required to maintain a pro-immunogenic phenotype after IFNγ withdrawal, since both could be prevented by JAKinibs with potency against JAK2. Finally, the suppressor of cytokine signaling SOCS1 failed to emerge in primed endothelial cells, which likely accounted for prolonged inflammatory gene expression. Conclusions: The results reveal a sustained JAK-dependent perturbation of endothelial function and suggest that JAKinibs may have therapeutic benefit in dampening vascular inflammation and allogeneic leukocyte activation.

Several pieces of evidence have shown the neurotrophic effect of erythropoietin (EPO) and its introduction in the therapeutic practice of neurological diseases. However, its usefulness in the treatment of spinocerebellar ataxia type 2 (SCA2) has not been proven despite the fact that it is endogenously reduced in these patients.The study aims to investigate the safety, tolerability, and clinical effects of a nasally administered recombinant EPO in SCA2 patients.Thirty-four patients were enrolled in this double-blind, randomized, placebo-controlled, phase I-II clinical trial of the nasally administered human-recombinant EPO (NeuroEPO) for 6 months. The primary outcome was the change in the spinocerebellar ataxia functional index (SCAFI), while other motor, neuropsychological, and oculomotor measures were assessed.The 6-month changes in SCAFI score were slightly higher in the patients allocated to NeuroEPO treatment than placebo in spite of the important placebo effect observed for this parameter. However, saccade latency was significantly decreased in the NeuroEPO group but not in placebo. The frequency and severity of adverse events were similar between both groups, without evidences of hematopoietic activity of the drug.This study demonstrated the safety and tolerability of NeuroEPO in SCA2 patients after 6 months of treatments and suggested a small clinical effect of this drug on motor and cognitive abnormalities, but confirmatory studies are warranted. © 2022 International Parkinson and Movement Disorder Society.

In 2019, while launching a multidisciplinary research project aimed at developing the Puna de Atacama region as a natural laboratory, investigators at the University of Atacama (Chile) conducted a bibliographic search identifying previously studied geographic points of the region and of potential interest for planetary science and astrobiology research. This preliminary work highlighted a significant absence of local institutional involvement in international publications. In light of this, a follow-up study was conducted to confirm or refute these first impressions, by comparing the search in two bibliographic databases: Web of Science and Scopus. The results show that almost 60% of the publications based directly on data from the Puna, the Altiplano, or the Atacama Desert with objectives related to planetary science or astrobiology do not include any local institutional partner (Argentina, Bolivia, Chile, and Peru). Indeed, and beyond the ethical questioning of international collaborations, Latin-American planetary science deserves a strategic structuring, networking, as well as a road map at national and continental scales, not only to enhance research, development, and innovation, but also to protect an exceptional natural heritage sampling extreme environmental niches on Earth. Examples of successful international collaborations such as the field of meteorites, terrestrial analogs, and space exploration in Chile or astrobiology in Mexico are given as illustrations and possible directions to follow to develop planetary science in South America. To promote appropriate scientific practices involving local researchers, possible responses at academic and institutional levels will eventually be discussed.

Body size and feeding morphology influence how animals partition themselves within communities. We tested the relationships among sex, body size, skull morphology and foraging in sympatric otariids (eared seals) from the eastern North Pacific Ocean, the most diverse otariid community in the world. We recorded skull measurements and stable carbon ( δ 13 C) and nitrogen ( δ 15 N) isotope values (proxies for foraging) from museum specimens in four sympatric species: California sea lions ( Zalophus californianus ), Steller sea lions ( Eumetopias jubatus ), northern fur seals ( Callorhinus ursinus ) and Guadalupe fur seals ( Arctocephalus townsendi ). Species and sexes had statistical differences in size, skull morphology and foraging significantly affecting the δ 13 C values. Sea lions had higher δ 13 C values than fur seals, and males of all species had higher values than females. The δ 15 N values were correlated with species and feeding morphology; individuals with stronger bite forces had higher δ 15 N values. We also found a significant community-wide correlation between skull length (indicator of body length), and foraging, with larger individuals having nearshore habitat preferences, and consuming higher trophic level prey than smaller individuals. Still, there was no consistent association between these traits at the intraspecific level, indicating that other factors might account for foraging variability.

BackgroundThe Receptor Binding Domain (RBD) of the SARS-CoV-2 spike protein is the target for many COVID-19 vaccines. Here we report results for phase 1 clinical trial of two COVID-19 vaccine candidates based on recombinant dimeric RBD (d-RBD).MethodsWe performed a randomized, double-blind, phase I clinical trial in the National Centre of Toxicology in Havana. Sixty Cuban volunteers aged 19-59 years were randomized into three groups (20 subjects each): 1) FINLAY-FR-1 (50 mcg d-RBD plus outer membrane vesicles from N. meningitidis); 2) FINLAY-FR-1A-50 mcg d-RBD (three doses); 3) FINLAY-FR-1A-25 mcg d-RDB (three doses). The FINLAY-FR-1 group was randomly divided to receive a third dose of the same vaccine candidate (homologous schedule) or of FINLAY-FR-1A-50 (heterologous schedule). The primary outcomes were safety and reactogenicity. The secondary outcome was vaccine immunogenicity. Humoral response at baseline and following each vaccination was evaluated using live-virus neutralization test, anti-RBD IgG ELISA and in-vitro neutralization test of RBD:hACE2 interaction.ResultsMost adverse events were of mild intensity (63.5%), solicited (58.8%), and local (61.8%); 69.4% with causal association with vaccination. Serious adverse events were not found. The FINLAY-FR-1 group reported more adverse events than the other two groups. After the third dose, anti-RBD seroconversion was 100%, 94.4% and 90% for the FINLAY-FR-1, FINLAY-FR-1A-50 and FINLAY-FR-1A-25 respectively. The in-vitro inhibition of RBD:hACE2 interaction increased after the second dose in all formulations. The geometric mean neutralizing titres after the third dose rose significantly in the group vaccinated with FINLAY-FR-1 with respect to the other formulations and the COVID-19 Convalescent Serum Panel. No differences were found between FINLAY-FR-1 homologous or heterologous schedules.ConclusionsVaccine candidates were safe and immunogenic, and induced live-virus neutralizing antibodies against SARS-CoV-2. The highest values were obtained when outer membrane vesicles were used as adjuvant.Trial registryhttps://rpcec.sld.cu/en/trials/RPCEC00000338-En

In-Cell Crosslinked Enzymes (InCLEs) is a procedure to improve the thermal and operational stability of Bacillus megaterium intracellular decarboxylase activity, allowing to obtain enhanced whole-cell biocatalyst to produce 4-vinyl guaiacol (4VG). InCLEs were achieved using a fixed amount of biomass in a two-step procedure: 1) permeation of the membrane cell for reactants diffusion, and 2) intracellular proteins crosslinking. To optimize InCLEs preparation, 7.68 mg of biomass in the presence of different ethanol concentrations (10–50% v/v) were permeated, subsequently, the intracellular proteins were crosslinked with a glutaraldehyde/biomass ratios of 0, 1.63 and 3.26 μmol/mg. At the best conditions (10% v/v ethanol and 1.63 μmol/mg), thermostability increases 4.7-fold against the permeated uncrosslinked biocatalyst (PUCB). To further enhance the stability, the internalization of different molecular weight polyethyleneimine (PEI, 1.09 mg/mL) was evaluated. PEI-InCLEs using 25 kDa PEI, showed a half-life 68-fold higher than PUCB (1 min) at 50 °C. After 7 cycles (26.3 mM ferulic acid, pH 7), PEI-InCLEs retained 83 and 69% of the decarboxylase activity at 40 and 50 °C, producing 32.7 and 29.8 μmol of 4VG, respectively. Here we demonstrated that the InCLEs procedure is an effective strategy to obtain stable whole-cell biocatalysts for the production of high-valued biotechnological molecules.

BackgroundNFκB drives acute vascular inflammation by activating gene expression programs in endothelial cells to promote leukocyte recruitment. Numerous negative feedback regulators of NFκB activation have been defined that promote resolution of inflammation. However, the identities of endogenous suppressors of NFκB transcription are less clear. In macrophages, the transcriptional repressor BCL6 was shown to substantially overlap with NFκB-driven genes and influence the response to LPS. We identified that the DNA binding protein BCL6 was expressed in endothelial cells. Although the role of BCL6 in adaptive immune cells has been characterized, how BCL6 modifies transcription in endothelial cells has not been studied.ObjectiveBased on prior knowledge that BCL6 represses part of the LPS-induced transcriptome in macrophages, we asked whether BCL6 regulated endothelial pro-inflammatory state by direct interaction with NFκB.MethodsWe analyzed public datasets of RNA and ChIP-Seq, probed BCL6 expression in human tissue, and tested BCL6 knockdown, overexpression and pharmacological manipulation on TNFα induced gene expressionin vitrousing human primary endothelium isolated from the heart.ResultsWe demonstrate that the DNA binding protein BCL6 is basally expressed in the endothelium, with chromatin marks reflective of a superenhancer, and is particularly enriched in aortic endothelial cells (ECs) compared with ECs from other organs. Although basal expression was relatively low, BCL6 was rapidly upregulated in cardiac endothelium stimulated with TNFα, through direct action of NFκB. The BCL6 consensus DNA binding motif overlaps with that of NFκB. BCL6 target genes included endothelial pro-inflammatory chemokines and adhesion molecules, as well as NFκB-related genes themselves. BCL6 knockdown and the degrading BCL6 inhibitor BI-3802 augmented the endothelial cell response to TNFα. Surprisingly, antagonism of the BTB domain of BCL6 with small molecules 79-6, FX1 or BI-3812, blocked leukocyte adherence and accordingly suppressed both NFκB transcriptional activity as well as the expression of many genes in response to TNFα. Lastly, we show that HDAC activity is increased by TNFα, and can be reduced in the presence of BTB domain inhibitors.ConclusionsOur results demonstrate that BCL6 is a repressor of NFκB-driven gene expression and inflammation in cardiac endothelial cells. These findings indicate that targeting of BCL6 may enhance vascular inflammation resolution.

BackgroundIFNγ induces an endothelial cell pro-immunogenic phenotype through the JAK/STAT1 pathway, which can influence alloreactive leukocytes in transplant rejection. Numerous endogenous suppressors of JAK and STAT activation have been described, but regulation of STAT1 at the level of transcription is not well-understood. In immune cells, the DNA binding protein BCL6 controls transcription of lineage and inflammatory genes, including STAT-dependent responses. The goal of this study was to determine if BCL6 also modulates the IFNγ-induced immunogenic phenotype in endothelium.MethodsBCL6 binding to target genes and similarity to STAT1 motifs was analyzedin silicousing public datasets.In vitro, primary human aortic endothelial cells were tested for expression of IFNγ-inducible costimulatory molecules, HLA and cytokines, under BCL6 overexpression, depletion and pharmacological targeting. Gene expression was measured by RNA-Seq and protein expression was confirmed by flow cytometry, Luminex and ELISA. Paired biopsies from stable and rejecting human cardiac allografts were compared for expression of BCL6, PD ligands, CXCL chemokines and HLA-DR in the vasculature.ResultsBCL6 expression is increased within human cardiac transplants during rejection, which is positively correlated with expression of interferon response gene HLA-DR in donor blood vessels. Further, BCL6 is IFNγ-inducible via JAK1/2 in endothelium. Next, the consensus DNA binding motif of BCL6 is highly similar to that of STAT1, and numerous interferon response genes harbor BCL6 DNA binding motifs. Depletion of BCL6 in endothelium results in augmentation, while overexpression causes suppression, of MHC class II, chemokine, and PD ligand expression. Unexpectedly, pharmacological targeting of the corepressor domain BTB domain of BCL6 also repressed many interferon response genes, particularly HLA class II, CXCR3 chemokines and PD-L2. On the other hand, BCL6 targeting did not impact inducible expression of any HLA class I genes, PD-L1 or CD40; and the effect is correlated with the presence of BCL6 binding motifs in or near affected genes.ConclusionOur results show for the first time that the transcriptional repressor BCL6 selectively controls the endothelial response to IFNγ. A better understanding of the endogenous mechanisms that regulate donor endothelial activation has the potential to discover new avenues to dampen transplant rejection, with broader relevance to other vascular inflammatory diseases.