Insufficient oxygen supply represents a relevant issue in several fields of human physiology and medicine. It has been suggested that the implantation of photosynthetic cells can provide oxygen to tissues in the absence of a vascular supply. This approach has been demonstrated to be successful in several in vitro and in vivo models; however, no data is available about their safety in human patients. Here, an early phase-1 clinical trial (ClinicalTrials.gov identifier: NCT03960164, https://clinicaltrials.gov/ct2/show/NCT03960164) is presented to evaluate the safety and feasibility of implanting photosynthetic scaffolds for dermal regeneration in eight patients with full-thickness skin wounds. Overall, this trial shows that the presence of the photosynthetic microalgae Chlamydomonas reinhardtii in the implanted scaffolds did not trigger any deleterious local or systemic immune responses in a 90 days follow-up, allowing full tissue regeneration in humans. The results presented here represent the first attempt to treat patients with photosynthetic cells, supporting the translation of photosynthetic therapies into clinics.

Establishing a node importance ranking is a problem that has attracted the attention of many researchers in recent decades. For unweighted networks where the edges do not have any attached weight, many proposals have been presented, considering local or global information of the networks. On the contrary, it occurs in undirected edge-weighted networks, where the proposals to address this problem have been more scarce. In this paper, a ranking method of node importance for undirected and edge-weighted is provided, generalizing the measure of line importance (DIL) based on the centrality degree proposed by Opsahl. The experimentation was done on five real networks and the results illustrate the benefits of our proposal.

Neuromodulation can profoundly impact the gain and polarity of postsynaptic changes in Hebbian synaptic plasticity. An emerging pattern observed in multiple central synapses is a pull–push type of control in which activation of receptors coupled to the G-protein Gs promote long-term potentiation (LTP) at the expense of long-term depression (LTD), whereas receptors coupled to Gq promote LTD at the expense of LTP. Notably, coactivation of both Gs- and Gq-coupled receptors enhances the gain of both LTP and LTD. To account for these observations, we propose a simple kinetic model in which AMPA receptors (AMPARs) are trafficked between multiple subcompartments in and around the postsynaptic spine. In the model AMPARs in the postsynaptic density compartment (PSD) are the primary contributors to synaptic conductance. During LTP induction, AMPARs are trafficked to the PSD primarily from a relatively small perisynaptic (peri-PSD) compartment. Gs-coupled receptors promote LTP by replenishing peri-PSD through increased AMPAR exocytosis from a pool of endocytic AMPAR. During LTD induction AMPARs are trafficked in the reverse direction, from the PSD to the peri-PSD compartment, and Gq-coupled receptors promote LTD by clearing the peri-PSD compartment through increased AMPAR endocytosis. We claim that the model not only captures essential features of the pull–push neuromodulation of synaptic plasticity, but it is also consistent with other actions of neuromodulators observed in slice experiments and is compatible with the current understanding of AMPAR trafficking.

Este artigo analisa e discute as produções acadêmicas da Educação Física sobre Educação Infantil a partir de uma breve apresentação e análise dos estudos que tomaram tal produção como tema de investigação. Em termos metodológicos se constitui numa revisão integrativa dos artigos, teses e dissertações que se propuseram a estudar a referida produção e estão disponíveis no Portal de Periódicos da CAPES, no Catálogo de Teses e Dissertações da CAPES e na Biblioteca Digital Brasileira de Teses e Dissertações (BDTD). Apresenta uma síntese e análise dos principais aspectos da produção que os estudos nos permitem conhecer, aponta algumas lacunas e indica algumas relações entre os referenciais teóricos que embasam as produções e as proposições apresentadas para a prática pedagógica da Educação com a Educação Infantil que vêm sendo sistematizadas. Conclui que, embora importante, a ênfase dada pelos estudos de revisão e estado da arte aos aspectos quantitativos e descritivos da produção tem dificultado uma compreensão mais abrangente dos discursos que são produzidos sobre a Educação Física na Educação Infantil.

Children born from women with preeclampsia have alterations in cerebral neurovascular development and a high risk for developing cognitive alterations. Because cerebral blood vessels are critical components in cerebrovascular development, we evaluated the brain microvascular perfusion and microvascular reactivity (exposed to external stimuli of warm and cold) in pups born to preeclampsia-like syndrome based on the reduction of uterine perfusion (RUPP). Also, we evaluate the angiogenic proteomic profile in those brains. Pregnant mice showed a reduction in uterine flow after RUPP surgery (−40 to 50%) associated with unfavorable perinatal results compared to sham mice. Furthermore, offspring of the RUPP mice exhibited reduced brain microvascular perfusion at postnatal day 5 (P5) compared with offspring from sham mice. This reduction was preferentially observed in females. Also, brain microvascular reactivity to external stimuli (warm and cold) was reduced in pups of RUPP mice. Furthermore, a differential expression of the angiogenic profile associated with inflammation, extrinsic apoptotic, cancer, and cellular senescence processes as the primary signaling impaired process was found in the brains of RUPP-offspring. Then, offspring (P5) from preeclampsia-like syndrome exhibit impaired brain perfusion and microvascular reactivity, particularly in female mice, associated with differential expression of angiogenic proteins in the brain tissue.

Breast cancer (BC) clinical guidelines offer evidence-based recommendations to improve quality of healthcare for patients with or at risk of BC. Suboptimal adherence to recommendations has the potential to negatively affect population health. However, no study has systematically reviewed the impact of BC guideline adherence -as prognosis factor- on BC healthcare processes and health outcomes. The objectives are to analyse the impact of guideline adherence on health outcomes and on healthcare costs.

Estrogenic steroids and adenosine A2A receptors promote the wound healing and angiogenesis processes. However, so far, it is unclear whether estrogen may regulate the expression and pro-angiogenic activity of A2A receptors. Using in vivo analyses, we showed that female wild type (WT) mice have a more rapid wound healing process than female or male A2A-deficient mice (A2AKO) mice. We also found that pulmonary endothelial cells (mPEC) isolated from female WT mice showed higher expression of A2A receptor than mPEC from male WT mice. mPEC from female WT mice were more sensitive to A2A-mediated pro-angiogenic response, suggesting an ER and A2A crosstalk, which was confirmed using cells isolated from A2AKO. In those female cells, 17β-estradiol potentiated A2A-mediated cell proliferation, an effect that was inhibited by selective antagonists of estrogen receptors (ER), ERα, and ERβ. Therefore, estrogen regulates the expression and/or pro-angiogenic activity of A2A adenosine receptors, likely involving activation of ERα and ERβ receptors. Sexual dimorphism in wound healing observed in the A2AKO mice process reinforces the functional crosstalk between ER and A2A receptors.

Alternative lengthening of telomeres (ALT) is a telomere maintenance mechanism activated in ~10–15% of cancers, characterized by telomeric damage. Telomeric damage-induced long non-coding RNAs (dilncRNAs) are transcribed at dysfunctional telomeres and contribute to telomeric DNA damage response (DDR) activation and repair. Here we observed that telomeric dilncRNAs are preferentially elevated in ALT cells. Inhibition of C-rich (teloC) dilncRNAs with antisense oligonucleotides leads to DNA replication stress responses, increased genomic instability, and apoptosis induction selectively in ALT cells. Cell death is dependent on DNA replication and is increased by DNA replication stress. Mechanistically, teloC dilncRNA inhibition reduces RAD51 and 53BP1 recruitment to telomeres, boosts the engagement of BIR machinery, and increases C-circles and telomeric sister chromatid exchanges, without increasing telomeric non-S phase synthesis. These results indicate that teloC dilncRNA is necessary for a coordinated recruitment of DDR factors to ALT telomeres and it is essential for ALT cancer cells survival. Similar content being viewed by others

Phenotypic plasticity allows carcinoma cells to transiently acquire the quasi-mesenchymal features necessary to detach from the primary mass and proceed along the invasion-metastasis cascade. A broad spectrum of epigenetic mechanisms is likely to cause the epithelial-to-mesenchymal (EMT) and mesenchymal-to-epithelial (MET) transitions necessary to allow local dissemination and distant metastasis. Here, we report on the role played by alternative splicing (AS) in eliciting phenotypic plasticity in epithelial malignancies with focus on colon cancer. By taking advantage of the coexistence of subpopulations of fully epithelial (EpCAMhi) and quasi-mesenchymal and highly metastatic (EpCAMlo) cells in conventional human cancer cell lines, we here show that the differential expression of ESRP1 and other RNA-binding proteins (RBPs) downstream of the EMT master regulator ZEB1 alters the AS pattern of a broad spectrum of targets including CD44 and NUMB, thus resulting in the generation of specific isoforms functionally associated with increased invasion and metastasis. Additional functional and clinical validation studies indicate that both the newly identified RBPs and the CD44s and NUMB2/4 splicing isoforms promote local invasion and distant metastasis and are associated with poor survival in colon cancer. The systematic elucidation of the spectrum of EMT-related RBPs and AS targets in epithelial cancers, apart from the insights in the mechanisms underlying phenotypic plasticity, will lead to the identification of novel and tumor-specific therapeutic targets.

The evaluation of white blood cells is essential to assess the quality of the human immune system; however, the assessment of the blood smear depends on the pathologist’s expertise. Most machine learning tools make a one-level classification for white blood cell classification. This work presents a two-stage hybrid multi-level scheme that efficiently classifies four cell groups: lymphocytes and monocytes (mononuclear) and segmented neutrophils and eosinophils (polymorphonuclear). At the first level, a Faster R-CNN network is applied for the identification of the region of interest of white blood cells, together with the separation of mononuclear cells from polymorphonuclear cells. Once separated, two parallel convolutional neural networks with the MobileNet structure are used to recognize the subclasses in the second level. The results obtained using Monte Carlo cross-validation show that the proposed model has a performance metric of around 98.4% (accuracy, recall, precision, and F1-score). The proposed model represents a good alternative for computer-aided diagnosis (CAD) tools for supporting the pathologist in the clinical laboratory in assessing white blood cells from blood smear images.

El principal objetivo fue determinar si existen diferencias en los niveles de actividad física (NAF) y la intención de ser físicamente activo entre países en función del género, curso y estatus socioeconómico. Participaron 3052 adolescentes (14.58 ± 1.39 años), 1516 chicos y 1536 chicas. Del total, 734 chilenos y 2318 españoles. Las variables medidas fueron los NAF con el “International Physical Activity Questionnaire- Short Form” (IPAQ-SF), la intención de ser físicamente activo con el “Intention to be Physically Active” y el estatus socioeconómico familiar con el “Family Affluence Scale II” (FASII). Se encontraron diferencias significativas en los NAF y en la intención de ser físicamente activo entre países en función del género (p < .001), curso (p < .001) y estatus socioeconómico (p < .01), siendo más altas en España. Además, la relación de cada una de estas variables con los NAF y la intencionalidad varía según el país. Como la relación de las variables sociodemográficas con los NAF y la intención de ser físicamente activo varía en función del país sería necesario llevar a cabo más estudios transculturales que permitan realizar intervenciones de promoción de actividad física y salud adaptadas a las necesidades de cada lugar. === The main goal was to analyze the physical activity levels and the intention to be physically active differences between both countries regarding the gender, course and socioeconomic status. The sample was 3,052 adolescents (14.58 ± 1.39 years), 1,516 males and 1,536 females. From the whole participants, 734 were Chilean and 2,318 Spanish. Physical activity levels were measured using the “International Physical Activity Questionnaire- Short Form” (IPAQ-SF), the intention to be physically active using the “Intention to be Physically Active” scale and the socioeconomic status using the “Family Affluence Scale II” (FASII). There are significant differences in physical activity levels and the intention to be physically active between both countries according to the gender (p < .001), course (p < .001) and socioeconomic status (p < .01). Data were higher in Spain than Chile. Moreover, the relation between these sociodemographic variables with physical activity levels and the intention to be physically active were different regarding the country. As the relation between these sociodemographic variables with physical activity levels and the intention to be physically active is different according to the country, cross-cultural researches are required to develop physical activity and health interventions adapted to people`s needs.

Clavibacter michiganensis subsp. michiganensis (Cmm) is the causal agent of bacterial canker of tomato. Differences in virulence between Cmm strains have been reported. The aim of this study was the characterization of nine Cmm strains isolated in Chile to reveal the causes of their differences in virulence. The virulence assays in tomato seedlings revealed different levels of severity associated with the strains, with two highly virulent strains and one causing only mild symptoms. The two most virulent showed increased cellulase activity, and no cellulase activity was observed in the strain causing mild symptoms. In three strains, including the two most virulent strains, PCR amplification of the 10 virulence genes analyzed was observed. In the strain causing mild symptoms, no amplification was observed for five genes, including celA. Sequence and cluster analyses of six virulence genes grouped the strains, as has been previously reported, except for gene pelA1. Gene sequence analysis from the genomes of five Chilean strains revealed the presence of deletions in the virulence genes, celB, xysA, pat-1, and phpA. The results of this study allow us to establish correlations between the differences observed in disease severity and the presence/absence of genes and deletions not previously reported.

BACKGROUND The antifeedant activity of 18 sesquiterpenoids of the drimane family (polygodial, drimenol and derivatives) was investigated. RESULTS Polygodial, drimanic and nordrimanic derivatives were found to exert antifeedant effects against two insect species, Spodoptera frugiperda and Epilachna paenulata, which are pests of agronomic interest, indicating that they have potential as biopesticide agents. Among the 18 compounds tested, the epoxynordrimane compound (11) and isonordrimenone (4) showed the highest activity [50% effective concentration (EC50) = 23.28 and 25.63 nmol cm−2, respectively, against S. frugiperda, and 50.50 and 59.00 nmol/cm2, respectively, against E. paenulata]. CONCLUSION The results suggest that drimanic compounds have potential as new agents against S. frugiperda and E. paenulata. A quantitative structure–activity relationship (QSAR) analysis of the whole series, supported by electronic studies, suggested that drimanic compounds have structural features necessary for increasing antifeedant activity, namely a C-9 carbonyl group and an epoxide at C-8 and C-9. © 2018 Society of Chemical Industry

Fungal diseases, both pre- and post-harvest, are currently difficult to control—increased antifungal resistances have further stimulated the search for natural alternatives. The objective of the present research work was to evaluate the antifungal activities of Mentha pulegium essential oil (EO) and its major constituents. The EO was obtained from hydro distillation of fresh leaves, and composition was determined using gas chromatography/mass spectrometry (GC/MS). The main components were identified as pulegone (29.33%), menthol (28.79%), menthone (20.48%), and isopulegol (9.75%). EO and isopulegol exhibited the highest antifungal activity, with half maximal effective concentrations (EC50) inhibiting mycelial activity of Monilinia fructicola at 24.6 µg/mL and 20.8 µg/mL, respectively, and against Botrytis cinerea, at 301.45 µg/mL and 333.84 µg/mL, respectively. These findings could lay the foundation for developing antifungal agents of agricultural value.

Tomatoes (Solanum lycopersicum L.) are the most cultivated and important vegetable crop in the world. These plants can wilt during crop growth due to fusarium wilt (fusariosis), a disease that damages tomato vascular systems. The Fusarium isolated and analyzed in this work correspond to Fusarium oxysporum f. sp. radicis-lycopersici. The isolates were molecularly identified, and analysis was done on the in vitro effects of the nanoemulsions (previously obtained from extracts of Chilean medicinal plants of the genera Psoralea and Escallonia) to inhibit mycelial and conidial germination of the isolates. Subsequently, the nanoemulsions were evaluated under greenhouse conditions for preventive control of fusariosis in the root and crown, with high levels of disease control observed using the highest concentrations of these nanoemulsions, at 250 and 500 ppm.

Leptocarpha rivularis is a native South American plant used ancestrally by Mapuche people to treat gastrointestinal ailments. L. rivularis flower extracts are rich in molecules with therapeutic potential, including the sesquiterpene lactone leptocarpin, which displays cytotoxic effects against various cancer types in vitro. However, the combination of active molecules in these extracts could offer a hitherto unexplored potential for targeting cancer. In this study, we investigated the effect of L. rivularis flower extracts on the proliferation, survival, and spread parameters of gastric cancer cells in vitro. Gastric cancer (AGS and MKN-45) and normal immortalized (GES-1) cell lines were treated with different concentrations of L. rivularis flower extracts (DCM, Hex, EtOAc, and EtOH) and we determined the changes in proliferation (MTS assay, cell cycle analysis), cell viability/cytotoxicity (trypan blue exclusion assay, DEVDase activity, mitochondrial membrane potential MMP, and clonogenic ability), senescence (β-galactosidase activity) and spread potential (invasion and migration assays using the Boyden chamber approach) in all these cells. The results showed that the DCM, EtOAc, and Hex extracts display a selective antitumoral effect in gastric cancer cells by affecting all the cancer parameters tested. These findings reveal an attractive antitumoral potential of L. rivularis flower extracts by targeting several acquired capabilities of cancer cells.

With the aging of the population, the number of older drivers is on the rise. This poses significant challenges for public health initiatives, as older drivers have a relatively higher risk for collisions. While many studies focus on developing screening tools to identify medically at-risk drivers, little research has been done to develop training programs or interventions to promote, maintain or enhance driving-related abilities among healthy individuals. The purpose of this systematic review is to synopsize the current literature on interventions that are tailored to improve driving in older healthy individuals by working on components of safe driving such as: self-awareness, knowledge, behaviour, skills and/or reducing crash/collision rates in healthy older drivers.

ImportanceContinuous glucose monitoring (CGM) devices have demonstrated efficacy in adults and more recently in youths and older adults with type 1 diabetes. In adults with type 1 diabetes, the use of real-time CGM compared with intermittently scanned CGM was associated with improved glycemic control, but there are limited data available for youths.ObjectiveTo assess real-world data on achievement of time in range clinical targets associated with different treatment modalities in youths with type 1 diabetes.Design, Setting, and ParticipantsThis multinational cohort study included children, adolescents, and young adults younger than 21 years (hereinafter referred to collectively as youths) with type 1 diabetes for a duration of at least 6 months who provided CGM data between January 1, 2016, and December 31, 2021. Participants were enrolled from the international Better Control in Pediatric and Adolescent Diabetes: Working to Create Centers of Reference (SWEET) registry. Data from 21 countries were included. Participants were divided into 4 treatment modalities: intermittently scanned CGM with or without insulin pump use and real-time CGM with or without insulin pump use.ExposuresType 1 diabetes and the use of CGM with or without an insulin pump.Main Outcomes and MeasuresProportion of individuals in each treatment modality group achieving recommended CGM clinical targets.ResultsAmong the 5219 participants (2714 [52.0%] male; median age, 14.4 [IQR, 11.2-17.1] years), median duration of diabetes was 5.2 (IQR, 2.7-8.7) years and median hemoglobin A1c level was 7.4% (IQR, 6.8%-8.0%). Treatment modality was associated with the proportion of individuals achieving recommended clinical targets. Adjusted for sex, age, diabetes duration, and body mass index standard deviation score, the proportion achieving the recommended greater than 70% time in range target was highest with real-time CGM plus insulin pump use (36.2% [95% CI, 33.9%-38.4%]), followed by real-time CGM plus injection use (20.9% [95% CI, 18.0%-24.1%]), intermittently scanned CGM plus injection use (12.5% [95% CI, 10.7%-14.4%]), and intermittently scanned CGM plus insulin pump use (11.3% [95% CI, 9.2%-13.8%]) (P &amp;lt; .001). Similar trends were observed for less than 25% time above (real-time CGM plus insulin pump, 32.5% [95% CI, 30.4%-34.7%]; intermittently scanned CGM plus insulin pump, 12.8% [95% CI, 10.6%-15.4%]; P &amp;lt; .001) and less than 4% time below range target (real-time CGM plus insulin pump, 73.1% [95% CI, 71.1%-75.0%]; intermittently scanned CGM plus insulin pump, 47.6% [95% CI, 44.1%-51.1%]; P &amp;lt; .001). Adjusted time in range was highest among real-time CGM plus insulin pump users (64.7% [95% CI, 62.6%-66.7%]). Treatment modality was associated with the proportion of participants experiencing severe hypoglycemia and diabetic ketoacidosis events.Conclusions and RelevanceIn this multinational cohort study of youths with type 1 diabetes, concurrent use of real-time CGM and an insulin pump was associated with increased probability of achieving recommended clinical targets and time in range target as well as lower probability of severe adverse events compared with other treatment modalities.

Astaxanthin (ASX) is a carotenoid pigment with strong antioxidant properties. We have reported previously that ASX protects neurons from the noxious effects of amyloid-β peptide oligomers, which promote excessive mitochondrial reactive oxygen species (mROS) production and induce a sustained increase in cytoplasmic Ca2+ concentration. These properties make ASX a promising therapeutic agent against pathological conditions that entail oxidative and Ca2+ dysregulation. Here, we studied whether ASX protects neurons from N-methyl-D-aspartate (NMDA)-induced excitotoxicity, a noxious process which decreases cellular viability, alters gene expression and promotes excessive mROS production. Incubation of the neuronal cell line SH-SY5Y with NMDA decreased cellular viability and increased mitochondrial superoxide production; pre-incubation with ASX prevented these effects. Additionally, incubation of SH-SY5Y cells with ASX effectively reduced the basal mROS production and prevented hydrogen peroxide-induced cell death. In primary hippocampal neurons, transfected with a genetically encoded cytoplasmic Ca2+ sensor, ASX also prevented the increase in intracellular Ca2+ concentration induced by NMDA. We suggest that, by preventing the noxious mROS and Ca2+ increases that occur under excitotoxic conditions, ASX could be useful as a therapeutic agent in neurodegenerative pathologies that involve alterations in Ca2+ homeostasis and ROS generation.

Antioxidants are known to be beneficial to health. This paper evaluates the potential chemopreventive and anticancer properties of phenolic compounds present in grape juice extracts (GJE) from Autumn Royal and Ribier varieties. The effects of these GJE on viability (SRB day assay) and metastatic potential (migration and invasion parameters) of colon cancer cell lines HT‐29 and SW‐480 were evaluated. The effects of GJE on two matrix metalloproteinase gene expressions (MMP2 and MMP9) were also evaluated via qRT‐PCR. In the former, GJE reduced cell viability in both cell lines in a dose‐dependent manner. GJE treatment also reduced cell migration and invasion. Moreover, MMP‐2 and MMP‐9 gene expression diminished depending on extract and on cell type.