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1.
Cell Rep ; 43(5): 114179, 2024 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-38691455

RESUMO

Plant pathogens manipulate host development, facilitating colonization and proliferation. Ralstonia solanacearum is a soil-borne bacterial pathogen that penetrates roots and colonizes plants through the vascular system, causing wilting and death. Here, we find that RipAC, an effector protein from R. solanacearum, alters root development in Arabidopsis, promoting the formation of lateral roots and root hairs. RipAC interacts with CELLULOSE SYNTHASE (CESA)-INTERACTIVE PROTEIN 1 (CSI1), which regulates the activity of CESA complexes at the plasma membrane. RipAC disrupts CESA-CSI1 interaction, leading to a reduction in cellulose content, root developmental alterations, and a promotion of bacterial pathogenicity. We find that CSI1 also associates with the receptor kinase FERONIA, forming a complex that negatively regulates immunity in roots; this interaction, however, is not affected by RipAC. Our work reveals a bacterial virulence strategy that selectively affects the activities of a host target, promoting anatomical alterations that facilitate infection without causing activation of immunity.

2.
Plant Physiol ; 2024 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-38378170

RESUMO

The root system plays an essential role in plant growth and adaptation to the surrounding environment. The root clock periodically specifies lateral root prebranch sites (PBS), where a group of pericycle founder cells (FC) is primed to become LR founder cells (LRFCs) and eventually give rise to lateral root primordia (LRP) or lateral roots (LRs). This clock-driven organ formation process is tightly controlled by modulation of auxin content and signaling. Auxin perception entails the physical interaction of TRANSPORT INHIBITOR RESPONSE 1 (TIR1) or AUXIN SIGNALING F-BOX (AFBs) proteins with AUXIN/INDOLE-3-ACETIC ACID (Aux/IAA) repressors to form a co-receptor system. Despite the apparent simplicity, the understanding of how specific auxin co- receptors are assembled remains unclear. We identified the compound bis-methyl auxin conjugated with N-glucoside, or BiAux, in Arabidopsis (Arabidopsis thaliana) that specifically induces the formation of PBS and the emergence of LR, with a slight effect on root elongation. Docking analyses indicated that BiAux binds to F-box proteins, and we showed that BiAux function depends on TIR1 and AFB2 F-box proteins and AUXIN RESPONSE FACTOR 7 (ARF7) activity, which is involved in FC specification and LR formation. Finally, using a yeast (Saccharomyces cerevisiae) heterologous expression system, we showed that BiAux favors the assemblage of specific co-receptors subunits involved in LR formation and enhances AUXIN/INDOLE-3-ACETIC ACID 28 (IAA28) protein degradation. These results indicate that BiAux acts as an allosteric modulator of specific auxin co-receptors. Therefore, BiAux exerts a fine-tune regulation of auxin signaling aimed to the specific formation of LR among the many development processes regulated by auxin.

3.
Nat Chem ; 16(3): 426-436, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38093093

RESUMO

The appeal of catalytic click chemistry is largely due to the copper-catalysed azide-alkyne cycloaddition (CuAAC) process, which is orthogonal to the more recently introduced sulfur-fluoride exchange (SuFEx). However, the triazole rings generated by CuAAC are not readily modifiable, and SuFEx connectors cannot be selectively functionalized, attributes that would be attractive in a click process. Here we introduce bisphosphine-copper-catalysed phenoxydiazaborinine formation (CuPDF), a link-and-in situ modify strategy for merging a nitrile, an allene, a diborane and a hydrazine. We also present copper- and palladium-catalysed quinoline formation (Cu/PdQNF), which is applicable in aqueous media, involving an aniline as the modifier. CuPDF and Cu/PdQNF are easy to perform and deliver robust, alterable and tunable fluorescent hubs. CuPDF and Cu/PdQNF are orthogonal to SuFEx and CuAAC, despite the latter and CuPDF also being catalysed by an organocopper species. These advantages were applied to protecting group-free syntheses of sequence-defined branched oligomers, a chemoselectively amendable polymer, three drug conjugates and a two-drug conjugate.

4.
Int J Clin Pharm ; 46(2): 382-389, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38112892

RESUMO

BACKGROUND: Clinical trials of atezolizumab for locally advanced or metastatic urothelial bladder cancer (mUBC) report controversial efficacy data. Furthermore, real-world evidence about this use is limited. AIM: We aimed to evaluate the effectiveness of atezolizumab in a real-world population with mUBC, to explore effectiveness with regard to selected poor prognostic criteria such as performance status by Eastern Oncology Cooperative Group (ECOG), hemoglobin levels and liver metastases, and to determine the safety profile of atezolizumab. METHOD: Multicenter, retrospective real-world study including previously treated mUBC patients who received atezolizumab. The primary endpoint was overall survival (OS). Additionally, progression-free survival (PFS), best response reached and safety data were analyzed. A descriptive analysis was performed, while OS and PFS were estimated by Kaplan-Meier method. RESULTS: A total of 185 patients (84.9% men, median age 69 years) were included. Median PFS was 4.8 months [95% confidence interval (CI) 3.6-6.0], and median OS was 20.0 months (95% CI 11.8-28.5), with an objective response rate of 28.1%. OS was higher for patients with ECOG 0-1 versus 2-3 [24.5 months (95% CI 14.5-34.6) vs. 5.2 (95% CI 4.4-6.0), p = 0.004]; and for patients without liver metastases [25.4 months (95% CI 16.2-34.6) vs. 6.4 months (95% CI 4.0-8.1), p = 0.006]. Regarding hemoglobin levels, no survival differences were detected. Adverse events were registered in 55.1% of patients. CONCLUSION: In a real-world population with previously treated mUBC, atezolizumab seems to provide clinically relevant benefit, which is even higher for patients with ECOG 0-1 and without liver metastases, with an acceptable safety profile.


Assuntos
Anticorpos Monoclonais Humanizados , Carcinoma de Células de Transição , Neoplasias Hepáticas , Neoplasias da Bexiga Urinária , Masculino , Humanos , Idoso , Feminino , Estudos Retrospectivos , Neoplasias da Bexiga Urinária/tratamento farmacológico , Neoplasias da Bexiga Urinária/patologia , Carcinoma de Células de Transição/tratamento farmacológico , Carcinoma de Células de Transição/patologia , Neoplasias Hepáticas/tratamento farmacológico , Hemoglobinas , Protocolos de Quimioterapia Combinada Antineoplásica
5.
Plant Commun ; 4(6): 100737, 2023 Nov 13.
Artigo em Inglês | MEDLINE | ID: mdl-37865820

RESUMO

Plant growth and development involve the specification and regeneration of stem cell niches (SCNs). Although plants are exposed to disparate environmental conditions, how environmental cues affect developmental programs and stem cells is not well understood. Root stem cells are accommodated in meristems in SCNs around the quiescent center (QC), which maintains their activity. Using a combination of genetics and confocal microscopy to trace morphological defects and correlate them with changes in gene expression and protein levels, we show that the cold-induced transcription factor (TF) C-REPEAT BINDING FACTOR 3 (CBF3), which has previously been associated with cold acclimation, regulates root development, stem cell activity, and regeneration. CBF3 is integrated into the SHORT-ROOT (SHR) regulatory network, forming a feedback loop that maintains SHR expression. CBF3 is primarily expressed in the root endodermis, whereas the CBF3 protein is localized to other meristematic tissues, including root SCNs. Complementation of cbf3-1 using a wild-type CBF3 gene and a CBF3 fusion with reduced mobility show that CBF3 movement capacity is required for SCN patterning and regulates root growth. Notably, cold induces CBF3, affecting QC activity. Furthermore, exposure to moderate cold around 10°C-12°C promotes root regeneration and QC respecification in a CBF3-dependent manner during the recuperation period. By contrast, CBF3 does not appear to regulate stem cell survival, which has been associated with recuperation from more acute cold (∼4°C). We propose a role for CBF3 in mediating the molecular interrelationships among the cold response, stem cell activity, and development.


Assuntos
Proteínas de Arabidopsis , Arabidopsis , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Proteínas de Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , Arabidopsis/metabolismo , Plantas/metabolismo , Células-Tronco
6.
Medisur ; 21(5)oct. 2023.
Artigo em Espanhol | LILACS-Express | LILACS | ID: biblio-1521213

RESUMO

Fundamento la toxicidad asociada a los tratamientos de quimioterapia y radioterapia eleva la morbilidad y la mortalidad en los pacientes oncológicos. Objetivo diseñar un modelo predictivo de toxicidad de la quimioterapia y la radioterapia en el paciente oncológico quirúrgico. Métodos estudio analítico, de casos y controles, en pacientes oncológicos quirúrgicos que cumplieron los criterios de inclusión para la predicción de toxicidad preoperatoria, en el periodo enero a diciembre de 2022, en el Hospital Provincial Docente Oncológico María Curie, de Camagüey. Mediante el paquete estadístico Statistical Package for the Social Sciences, se seleccionó una muestra aleatoria de 334 pacientes, 197 sin toxicidad (grupo control) y 137 con toxicidad (grupo de estudio). Se realizó estimación de predictores de toxicidad mediante regresión logística binaria. Se seleccionó el modelo de mejor ajuste. Resultados el modelo en el paso tres predice un porcentaje global de 83,5 % con respecto a los valores observados. La sensibilidad resultó ser de 81,8; y la especificidad, 84,8. El modelo presentó buen poder discriminativo. Las variables en la ecuación fueron: hipertensión arterial, fracción de eyección del ventrículo izquierdo y anemia. La comparación de la predicción con la realidad, mediante curva Receiver Operating Characteristic determinó un área bajo la curva de 0,901. Conclusión se obtuvo una función de regresión logística que permitió la estimación de la probabilidad de toxicidad en pacientes oncológicos quirúrgicos electivos, la cual proporcionó una herramienta para su predicción desde el preoperatorio.


Foundation the toxicity associated with chemotherapy and radiotherapy treatments increases morbidity and mortality in cancer patients. Objective to design a predictive model of chemotherapy and radiotherapy toxicity in surgical cancer patients. Methods analytical, case-control study, in surgical oncology patients who met the inclusion criteria for the prediction of preoperative toxicity, from January to December 2022, at the María Curie Provincial Teaching Oncology Hospital in Camagüey. Using the Statistical Package for the Social Sciences, a random sample of 334 patients was selected, 197 without toxicity (control group) and 137 with toxicity (study group). Toxicity predictors were estimated using binary logistic regression. The model with the best fit was selected. Results the model in step three predicts an overall percentage of 83.5% with respect to the observed values. The sensitivity turned out to be 81.8; and the specificity, 84.8. The model presented good discriminative power. The variables in the equation were: arterial hypertension, left ventricular ejection fraction, and anemia. The comparison of the prediction with reality, using the Receiver Operating Characteristic curve, determined an area under the curve of 0.901. Conclusion a logistic regression function was obtained that allowed the estimation of the toxicity probability elective surgical cancer patients, which provided a tool for its prediction from the preoperative period.

7.
Dermatitis ; 2023 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-37695812

RESUMO

Background: Dupilumab is an effective treatment for atopic dermatitis (AD) and it also restores skin barrier function. Nevertheless, early changes in epidermal barrier parameters related to sustained treatment response or treatment failure are not known. So, the objective of this study is to evaluate whether changes in skin barrier function after 16 weeks dupilumab treatment could predict sustained treatment response or treatment failure. Materials and Methods: A prospective observational study was conducted that included patients with AD starting dupilumab. Clinical scores, patient-reported outcome measures (PROMs), and skin barrier function parameters were assessed at baseline and after 16 weeks treatment. Patients were followed until they failed to dupilumab or until the end of the study period. Participants were divided into 2 groups: patients with treatment failure and those with sustained treatment response. Results: In total, 32 patients with AD were included in the study, with a mean age of 28.03 years (standard deviation 10.65), being 20 (60.6%) females. In total, 22 (66.7%) patients sustained dupilumab response during the study period and only 10 (33.3%) failed to treatment. After 16 weeks treatment, clinical scores were improved in both groups. Patients with sustained treatment response increased stratum corneum hydration (SCH) on noninvolved skin (34.25 arbitrary units [AU] vs 44.90AU, P = 0.001) and on eczematous lesions (20.71 AU vs 40.94 AU, P < 0.001) and also decreased transepidermal water loss (TEWL) on eczematous lesions (28.22 g/[m2·h] vs 14.83 g/[m2·h], P = 0.002). Patients with treatment failure did not change TEWL or SCH. SCH after 16 weeks treatment on noninvolved skin (odds ratio [OR] = 0.83, P = 0.018) and SCH after 16 weeks treatment on eczematous lesions (OR = 0.86, P = 0.028) were related to dupilumab failure. Conclusion: SCH could be used as a predictive biomarker of dupilumab response in patients with AD.

9.
Artigo em Inglês | MEDLINE | ID: mdl-36834203

RESUMO

Chronic Spontaneous Urticaria (CSU) leads to a decreased quality of life in patients because of pruritus and skin lesions. However, there is still little evidence on the impact that a worse sleep quality could have on the quality of life and emotional disorders in these patients. The aims of the present study are to analyze the potential impact of sleep quality on the quality-of-life and emotional status of patients with CSU. A cross-sectional study of 75 CSU patients was performed. Socio-demographic variables and disease activity, quality of life, sleep, sexual disfunction, anxiety, depression and personality traits were collected. A majority of 59 of the patients suffered from poor sleep quality. Sleep quality impairment was associated with worse disease control, greater pruritus and swelling and poorer general and urticaria-related quality-of-life (p < 0.05). Patients with poor sleep quality showed an increased prevalence of anxiety (1.62-fold) and depression risk (3.93-fold). Female sexual dysfunction, but not male, was found to be linked to poorer sleep quality (p = 0.04). To conclude, sleep quality impairment in patients with CSU is related to poor quality-of-life, worse disease control and higher rates of anxiety and depression. Global management of the disease should take sleep quality into account to improve the care of CSU patients.


Assuntos
Urticária Crônica , Distúrbios do Início e da Manutenção do Sono , Humanos , Feminino , Qualidade de Vida , Estudos Transversais , Qualidade do Sono , Doença Crônica , Prurido
11.
Plant Commun ; 4(3): 100514, 2023 05 08.
Artigo em Inglês | MEDLINE | ID: mdl-36585788

RESUMO

Climate change is increasing the frequency of extreme heat events that aggravate its negative impact on plant development and agricultural yield. Most experiments designed to study plant adaption to heat stress apply homogeneous high temperatures to both shoot and root. However, this treatment does not mimic the conditions in natural fields, where roots grow in a dark environment with a descending temperature gradient. Excessively high temperatures severely decrease cell division in the root meristem, compromising root growth, while increasing the division of quiescent center cells, likely in an attempt to maintain the stem cell niche under such harsh conditions. Here, we engineered the TGRooZ, a device that generates a temperature gradient for in vitro or greenhouse growth assays. The root systems of plants exposed to high shoot temperatures but cultivated in the TGRooZ grow efficiently and maintain their functionality to sustain proper shoot growth and development. Furthermore, gene expression and rhizosphere or root microbiome composition are significantly less affected in TGRooZ-grown roots than in high-temperature-grown roots, correlating with higher root functionality. Our data indicate that use of the TGRooZ in heat-stress studies can improve our knowledge of plant response to high temperatures, demonstrating its applicability from laboratory studies to the field.


Assuntos
Ecossistema , Raízes de Plantas , Temperatura , Raízes de Plantas/metabolismo , Meristema , Temperatura Alta , Plantas
12.
Eur Respir J ; 61(3)2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36396142

RESUMO

BACKGROUND: The primary aim of our study was to investigate the association between intubation timing and hospital mortality in critically ill patients with coronavirus disease 2019 (COVID-19)-associated respiratory failure. We also analysed both the impact of such timing throughout the first four pandemic waves and the influence of prior noninvasive respiratory support on outcomes. METHODS: This is a secondary analysis of a multicentre, observational and prospective cohort study that included all consecutive patients undergoing invasive mechanical ventilation due to COVID-19 from across 58 Spanish intensive care units (ICUs) participating in the CIBERESUCICOVID project. The study period was between 29 February 2020 and 31 August 2021. Early intubation was defined as that occurring within the first 24 h of ICU admission. Propensity score matching was used to achieve a balance across baseline variables between the early intubation cohort and those patients who were intubated after the first 24 h of ICU admission. Differences in outcomes between early and delayed intubation were also assessed. We performed sensitivity analyses to consider a different time-point (48 h from ICU admission) for early and delayed intubation. RESULTS: Of the 2725 patients who received invasive mechanical ventilation, a total of 614 matched patients were included in the analysis (307 for each group). In the unmatched population, there were no differences in mortality between the early and delayed groups. After propensity score matching, patients with delayed intubation presented higher hospital mortality (27.3% versus 37.1%; p=0.01), ICU mortality (25.7% versus 36.1%; p=0.007) and 90-day mortality (30.9% versus 40.2%; p=0.02) compared with the early intubation group. Very similar findings were observed when we used a 48-h time-point for early or delayed intubation. The use of early intubation decreased after the first wave of the pandemic (72%, 49%, 46% and 45% in the first, second, third and fourth waves, respectively; first versus second, third and fourth waves p<0.001). In both the main and sensitivity analyses, hospital mortality was lower in patients receiving high-flow nasal cannula (HFNC) (n=294) who were intubated earlier. The subgroup of patients undergoing noninvasive ventilation (n=214) before intubation showed higher mortality when delayed intubation was set as that occurring after 48 h from ICU admission, but not when after 24 h. CONCLUSIONS: In patients with COVID-19 requiring invasive mechanical ventilation, delayed intubation was associated with a higher risk of hospital mortality. The use of early intubation significantly decreased throughout the course of the pandemic. Benefits of such an approach occurred more notably in patients who had received HFNC.


Assuntos
COVID-19 , Ventilação não Invasiva , Insuficiência Respiratória , Humanos , Estudos Prospectivos , Pandemias , Intubação Intratraqueal/efeitos adversos , Respiração Artificial/efeitos adversos , Insuficiência Respiratória/terapia , Insuficiência Respiratória/etiologia , Unidades de Terapia Intensiva
13.
Dermatology ; 239(2): 255-261, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36470224

RESUMO

BACKGROUND: Surgery is an essential part of hidradenitis suppurativa (HS) treatment. Understanding and reducing surgical recurrence are crucial to obtaining the best results in patients' treatment. OBJECTIVE: The aim of the study was to characterize surgical recurrences in a cohort of patients with HS treated with wide excision and second-intention healing. METHODS: A prospective nested case-control study was conducted. A cohort of patients with HS treated with wide excision and second-intention healing was monitored for 68 weeks. The surgical procedure was classified as case (recurrence) or control (no recurrence). The type of recurrence was classified according to the elementary lesion in tunnel or abscess and inflammatory nodule (AN) recurrence. Sociodemographic and clinical data likely related to recurrence and the type of recurrence were evaluated. RESULTS: Sixty-three patients were included, receiving a total of 82 surgical procedures. The mean age of the patients was 36.18 years, and the surgical site presented a Hurley stage II severity in 79.26% (65/82) of the interventions. Tunnel recurrence was observed in 8.5% (7/82) and AN recurrence in 15.85% (13/82) of the interventions. Obesity was associated with a higher risk of recurrence, for both tunnel and AN recurrence. Hurley III at the surgical site, a history of pilonidal sinus, and higher International Hidradenitis Suppurativa Severity Score System (IHS4) after surgery and at week 68 increased the risk of tunnel recurrence. CONCLUSION: We propose classifying surgical recurrence based on the elemental type of lesion. Tunnel recurrence could originate in the depth of the surgical scar and could be associated with both surgical site factors and inflammatory load. AN recurrence could originate in the borders of the surgical scar and may particularly benefit from preoperative ultrasound.


Assuntos
Hidradenite Supurativa , Humanos , Adulto , Hidradenite Supurativa/complicações , Cicatriz , Estudos de Casos e Controles , Estudos Prospectivos , Índice de Gravidade de Doença
14.
Dermatology ; 239(1): 52-59, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-35998603

RESUMO

BACKGROUND: Hidradenitis suppurativa (HS) is a chronic inflammatory disease of the hair follicle which presents with painful nodules, abscesses, and fistulae in apocrine gland-bearing areas of the skin. Approved treatments include antibiotics and biologic drugs such as adalimumab. Despite these treatments, HS management is challenging. Acitretin is an oral retinoid used for its management as 3rd or 4th line therapy. There is little evidence regarding the effectiveness and safety of acitretin treatment for HS, and no reports have previously explored the potential clinical predictors associated with the response to the treatment. METHODS: Retrospective cohort study to assess the effectiveness and safety of acitretin treatment in HS patients who failed to respond to topical therapies. RESULTS: Sixty-two patients with moderate to severe HS were included. A significant decrease in the International HS Severity Scoring System (IHS4) score was found over time. Higher basal IHS4 score, family history of HS, follicular phenotype, and history of follicular plugging conditions were potential predictors of response. Most patients did not suffer any adverse events, and no severe side effects were observed. The main cause of discontinuation was lack of efficacy. CONCLUSION: Acitretin can be considered as a therapeutic option for patients with HS. The presence of follicular phenotype or a history of components of follicular occlusion syndrome is associated with better outcomes.


Assuntos
Hidradenite Supurativa , Humanos , Hidradenite Supurativa/complicações , Acitretina/efeitos adversos , Estudos de Coortes , Estudos Retrospectivos , Adalimumab/uso terapêutico , Índice de Gravidade de Doença , Resultado do Tratamento
15.
Front Pediatr ; 10: 975947, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36467484

RESUMO

Background: Campomelic dysplasia (CD) is a rare disorder that involves the skeletal and genital systems. This condition has been associated with a diverse set of mutations in the SRY-box transcription factor 9 (SOX9) gene. Case presentation: We herein report a case involving a 4-year-old female patient with CD, female sex reversal, type 1 Arnold-Chiari malformation, and bilateral conductive hearing loss and investigate the causal mutation. Whole-exome sequencing analysis detected a novel Trp115X* variant in the SOX9 gene. We performed a literature review of the reported cases and demonstrated that the missense variants were located only in the self-dimerization domain (DIM) and high-mobility group box domains. We also reported that variants in the DIM domain do not cause sex reversal and identified that the amino acid sequences that were mutated in the patients with campomelic dysplasia are evolutionarily conserved among primates. Conclusions: We suggest that missense variants cannot be located in the K2, PQA, and PQS given that these domains function critically for transcriptional activation or repression of target genes and evolve under purifying selection.

16.
Nat Chem ; 14(12): 1459-1469, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-36376387

RESUMO

Molecules that contain one or more fluorine atoms are crucial to drug discovery. There are protocols available for the selective synthesis of different organofluorine compounds, including those with a fluoro-substituted or a trifluoromethyl-substituted stereogenic carbon centre. However, approaches for synthesizing compounds with a trifluoromethyl- and fluoro-substituent stereogenic carbon centre are far less common. This potentially impactful set of molecules thus remains severely underdeveloped. Here we introduce a catalytic regio-, diastereo- and enantioselective strategy for the preparation of homoallylic alcohols bearing a stereogenic carbon centre bound to a trifluoromethyl group and a fluorine atom. The process, which involves a polyfluoroallyl boronate and is catalysed by an in situ-formed organozinc complex, can be used for diastereodivergent preparation of tetrafluoro-monosaccharides, including ribose core analogues of the antiviral drug sofosbuvir (Sovaldi). Unexpected reactivity/selectivity profiles, probably originating from the trifluoromethyl- and fluoro-substituted carbon site, are discovered, foreshadowing other unique chemistries that remain unknown.


Assuntos
Carbono , Flúor , Estereoisomerismo , Estrutura Molecular , Catálise
18.
Heliyon ; 8(6): e09798, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35800722

RESUMO

Although video games are increasing their presence in teens/children's private entertainment and there is ample evidence to support their educational possibilities, they are seldom introduced in classrooms. One of the least studied factors relative to the insertion of video games in curricula is teachers' conceptions on their effectiveness to foster learning. In this study, we investigate how teachers conceive of the educational usage of video games, considering their reported value and which video game dimensions are reflected to be of importance, as well as personal traits linked to them (gender, educational level, area of knowledge, teaching experience, behavioral intention ...). We designed a Likert questionnaire with three main dimensions: pragmatic play, epistemic play, and learning outcomes (verbal information, skills, and attitudes). 595 Spanish teachers answered the questionnaire online. We applied ANOVA and multiple regression techniques, which revealed a broad acceptance of video games as educational media. The most relevant analyzed factors turned out to be the intention to use video games in classrooms, and the private use of video games. Teachers believe that video games promote more learning when played with an epistemic goal, mediated by scaffolding and especially under the teacher's guidance, compared to pragmatic play related to completion and success in the game. They also consider video games to mainly promote verbal information learning, procedural learning, and finally attitude learning, with the latter being less probable. We suggest the need to strengthen not only teacher training programs in the educational use of video games but also research on relationships between teachers' beliefs and practices in order to convert these favorable beliefs into actual real practices.

19.
Front Plant Sci ; 13: 918537, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35845642

RESUMO

Climate change is a major threat to crop productivity that negatively affects food security worldwide. Increase in global temperatures are usually accompanied by drought, flooding and changes in soil nutrients composition that dramatically reduced crop yields. Against the backdrop of climate change, human population increase and subsequent rise in food demand, finding new solutions for crop adaptation to environmental stresses is essential. The effects of single abiotic stress on crops have been widely studied, but in the field abiotic stresses tend to occur in combination rather than individually. Physiological, metabolic and molecular responses of crops to combined abiotic stresses seem to be significantly different to individual stresses. Although in recent years an increasing number of studies have addressed the effects of abiotic stress combinations, the information related to the root system response is still scarce. Roots are the underground organs that directly contact with the soil and sense many of these abiotic stresses. Understanding the effects of abiotic stress combinations in the root system would help to find new breeding tools to develop more resilient crops. This review will summarize the current knowledge regarding the effects of combined abiotic stress in the root system in crops. First, we will provide a general overview of root responses to particular abiotic stresses. Then, we will describe how these root responses are integrated when crops are challenged to the combination of different abiotic stress. We will focus on the main changes on root system architecture (RSA) and physiology influencing crop productivity and yield and convey the latest information on the key molecular, hormonal and genetic regulatory pathways underlying root responses to these combinatorial stresses. Finally, we will discuss possible directions for future research and the main challenges needed to be tackled to translate this knowledge into useful tools to enhance crop tolerance.

20.
J Clin Med ; 11(12)2022 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-35743415

RESUMO

Epidermal barrier dysfunction plays an important role in atopic dermatitis (AD). The difficulty of objectively assessing AD severity and the introduction of new biologicals into clinical practice highlight the need to find parameters to monitor clinical outcomes. The aim of this study is to evaluate the impact of dupilumab on skin barrier function and compare it with other treatments in patients with AD. A prospective observational study was conducted in adults with AD treated with topical corticosteroids (TCS), cyclosporine, or dupilumab. The main outcome measures after 16 weeks of treatment were Eczema Area and Severity (EASI)-50 (50% improvement in EASI), and transepidermal water loss (TEWL)-50 (50% improvement in TEWL). Forty-six patients with AD were included in the study. The proportion of patients who achieved EASI-50 at week 16 was significantly higher in patients receiving dupilumab (81.8% vs. 28.6% vs. 40%, p = 0.004). In eczematous lesions, TEWL decreased in patients receiving dupilumab (31.02 vs. 12.10 g·h−1·m−2, p < 0.001) and TCS (25.30 vs. 14.88 g·h−1·m−2, p = 0.047). The proportion of patients who achieved TEWL-50 at week 16 was higher for dupilumab than for cyclosporine or TCS. Temperature only decreased in the dupilumab group. Stratum corneum hydration increased in eczematous lesions and non-involved skin only in patients with dupilumab. In conclusion, dupilumab improves skin barrier function in patients with AD better than TCS or cyclosporine, both in eczematous lesions and in non-lesioned skin.

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