Metabolomics Reveals Tyrosine Kinase Inhibitor Resistance-Associated Metabolic Events in Human Metastatic Renal Cancer Cells.

The development of resistance to tyrosine kinase inhibitors (TKIs) is a major cause of treatment failure in metastatic renal cell carcinoma (mRCC). A deeper understanding of the metabolic mechanisms associated with TKI resistance is critical for refining therapeutic strategies. In this study, we established resistance to sunitinib and pazopanib by exposing a parental Caki-1 cell line to increasing concentrations of sunitinib and pazopanib. The intracellular and extracellular metabolome of sunitinib- and pazopanib-resistant mRCC cells were investigated using a nuclear magnetic resonance (NMR)-based metabolomics approach. Data analysis included multivariate and univariate methods, as well as pathway and network analyses. Distinct metabolic signatures in sunitinib- and pazopanib-resistant RCC cells were found for the first time in this study. A common metabolic reprogramming pattern was observed in amino acid, glycerophospholipid, and nicotinate and nicotinamide metabolism. Sunitinib-resistant cells exhibited marked alterations in metabolites involved in antioxidant defence mechanisms, while pazopanib-resistant cells showed alterations in metabolites associated with energy pathways. Sunitinib-resistant RCC cells demonstrated an increased ability to proliferate, whereas pazopanib-resistant cells appeared to restructure their energy metabolism and undergo alterations in pathways associated with cell death. These findings provide potential targets for novel therapeutic strategies to overcome TKI resistance in mRCC through metabolic regulation.

Improving retrospective intervention descriptions: Lessons learned from research on type 2 diabetes programmes in the United Kingdom and the Republic of Ireland.

In recent years, multiple countries worldwide have implemented behavioural interventions within national healthcare systems. Describing the content of these interventions is critical to improve their implementation, replication, and effectiveness, as well as to advance behavioural science. Tools, such as the Behaviour Change Technique Taxonomy, can enhance the quality of intervention description and reporting. As interventions are frequently developed without the use of such tools, retrospective coding of existing interventions to accurately characterise their content is becoming more common. However, the use of these tools for retrospective coding poses various challenges, the discussion of which has been neglected to date. This commentary discusses the challenges encountered when retrospectively describing the content of five nationally implemented programmes for type 2 diabetes in the United Kingdom and the Republic of Ireland and suggests recommendations to tackle these challenges. We present important methodological, practical, and ethical considerations for researchers to reflect on, relevant to the retrospective description of existing interventions. Specifically, we discuss (i) the importance of positive relationships and collaboration with intervention stakeholders, (ii) the practical and ethical considerations when analysing the content of implemented interventions, (iii) the independence of research teams and the potential for misclassification of intervention content, and (iv) the challenges associated with the analysis of intervention content using behavioural science tools. There is a growing demand for more robust approaches to address the methodological, practical, and ethical challenges associated with such studies. The present commentary describes key issues to be considered by research teams, as well as concrete recommendations to improve the retrospective characterisation of intervention content.

In this commentary, we discuss how researchers can best describe the content of existing behavioural interventions. We talk about the challenges we faced when analysing behavioural interventions for type 2 diabetes prevention and management in the United Kingdom and the Republic of Ireland. Specifically, we reflect on the importance of building good relationships and collaborating with those responsible for developing and/or delivering the interventions, important practical and ethical considerations, dealing with research team independence, and using behavioural science tools to guide the analysis of intervention content. We also share what we have learned from these experiences and some ideas on how to tackle these challenges. Our experiences and lessons can offer valuable insights for future analyses of existing interventions.

Perspectives of People with Stroke, Caregivers and Healthcare Professionals on an Adaptive mHealth Intervention for Physical Activity in the Prevention of Secondary Stroke: A Qualitative Study.

Introduction: Engaging in regular physical activity (PA) is associated with lower mortality following stroke, and PA reduces the chance of recurrent stroke. Despite recent guidelines to optimise PA following stroke, people with stroke are known to be less active than their age-matched counterparts. Given the heterogenous nature of stroke, adaptive PA interventions are recommended for people with stroke. Empirical data is lacking on adaptive PA or behavioural change interventions following stroke. Suggested strategies in the prevention of stroke recommend the use of mobile health (mHealth) interventions in the primary prevention of stroke. A structured stakeholder consultation process is key to successful implementation of complex interventions. This paper reports the findings of our consultation process to inform the development of an adaptive mHealth PA. Methods: We used a qualitative study design to explore the perspectives of key stakeholders on the development of an adaptive PA intervention delivered via mHealth post-stroke. Healthcare workers, carers and people with stroke participated in semi-structured one-to-one or focus group interviews. A reflexive thematic analysis was undertaken on transcribed interviews; key themes and sub-themes were developed using coding and summarised by two researchers, then reviewed by the full research team. Results: Twenty-eight stakeholders were interviewed and three main themes were identified; Key feature of a mHealth intervention, delivering a mHealth intervention, Challenges to development and use. There was widespread agreement across stakeholder groups that an adaptive mHealth PA intervention following stroke would be beneficial to people with stroke, following discharge from acute care. Conclusion: Our consultation supports the development of an adaptive PA programme that addresses specific impairments that can hinder exercise participation after stroke.

Systematic documentation of the introduction of COVID-19 vaccines in Latin America and the Caribbean.

Objective: To document the process of introducing COVID-19 vaccines in a selection of Latin American and Caribbean countries, including the lessons learned and the strengths and weaknesses, and similarities and differences among programs. Methods: This descriptive study is based on a systematic evaluation of the process of introducing COVID-19 vaccines in Argentina, Belize, Brazil, Costa Rica, Panama and Peru. Data were collected through a questionnaire distributed to key stakeholders. Six informants from each of the included countries participated in this study. The period of the study was from December 2021 through September 2022. Results: The main strengths reported by countries were health workers' commitment to delivering vaccinations, evidence-based decision-making, the development of plans for vaccine introduction, the participation of national immunization technical advisory groups, the availability of economic resources and positive actions from the respective Ministry of Health. The main challenges were the actions of antivaccination groups, problems with electronic immunization registries, a lack of vaccines, delays in the delivery of vaccines and the scarcity of health personnel at the local level. Conclusions: Commitment, the participation of multiple sectors, the availability of resources and preparedness planning were some of the many strengths shown by countries introducing COVID-19 vaccines. Weaknesses included third parties' interests, the lack of information systems and difficulty in accessing vaccines and vaccine services. There is a window of opportunity for countries to maintain the good practices that allowed for the processes' strengths and to assess the identified weaknesses to invigorate immunization programs and prepare for future health crises.

Integrated Ca, Mg, Cu, and Zn supply upregulates leaf anatomy and metabolic adjustments in Eucalyptus seedlings.

Adaptive responses to abiotic stresses such as soil acidity in Eucalyptus-the most widely planted broad-leaf forest genus globally-are poorly understood. This is particularly evident in physiological and anatomical disorders that inhibit plant development and wood quality. We aimed to explore how the supply of Ca and Mg through liming (lime), combined with Cu and Zn fertilization (CZF), influences physiological and anatomical responses during Eucalyptus grandis seedlings growth in tropical acid soil. Therefore, related parameters of leaf area and leaf anatomy, stomatal size, leaf gas exchange, antioxidant system, nutrient partitioning, and biomass allocation responses were monitored. Liming alone in Eucalyptus increased specific leaf area, stomatal density on the abaxial leaf surface, and Ca and Mg content. Also, Eucalyptus exposed only to CZF increased Cu and Zn content. Lime and CZF increased leaf blade and adaxial epidermal thickness, and improved the structural organization of the spongy mesophyll, promoting increased net CO2 assimilation, and stomatal conductance. Fertilization with Ca, Mg, Cu, and Zn positively affects plant nutrition, light utilization, photosynthetic rate, and antioxidant performance, improving growth. Our results indicate that lime and CZF induce adaptive responses in the physiological and anatomical adjustments of Eucalyptus plantation, thereby promoting biomass accumulation.

Hyperfunctioning papillary thyroid carcinoma - a case report and literature review.

BACKGROUND: Malignant hyperfunctioning thyroid nodules are rare and more likely to occur in follicular cancer types rather than papillary variants. The authors present a case of a papillary thyroid carcinoma associated with a hyperfunctioning nodule. METHODS: A single adult patient submitted to total thyroidectomy with the presence of thyroid carcinoma within hyperfunctioning nodules was selected. Additionally, brief literature was conducted. RESULTS: An asymptomatic 58-year-old male was subjected to routine blood analysis and a TSH level of <0.003 mIU/L was found. Ultrasonography revealed a 21 mm solid, hypoechoic, and heterogenous nodule with microcalcifications in the right lobe. A fine needle aspiration guided by ultrasound resulted in a follicular lesion of undetermined significance. A 99mTc thyroid scintigram was followed and identified a right-sided hyperfunctioning nodule. Another cytology was performed and a papillary thyroid carcinoma was derived as a result. The patient underwent a total thyroidectomy. Postoperative histology confirmed the diagnosis and a tumor-free margin with no vascular or capsular invasions. CONCLUSION: Hyperfunctioning malignant nodules are a rare association, although a careful approach should be led since major clinical implications arise. Selective fine needle aspiration in all suspicious ≥1 cm nodules should be considered.

Enablers and barriers to accessing self-management support services for those living with and beyond cancer: A qualitative study using the theoretical domains framework.

BACKGROUND: Supporting those living with and beyond cancer to self-manage their health can optimise health-related quality of life and reduce symptom burden. Self-management support (SMS) programmes have been shown to be effective, but uptake is often low. This qualitative study aimed to identify experienced and perceived enablers and barriers to accessing SMS services among those who had completed primary cancer treatment and were living with and beyond cancer. METHODS: Participants were recruited through social media and cancer advocacy groups. Semi-structured telephone and online interviews were conducted. Transcripts were coded inductively based on participants' reported experiences. Statements related to factors that enable or inhibit access to SMS were then mapped to the Theoretical Domains Framework (TDF). RESULTS: Twenty-six people participated. Six themes explain the factors that act as barriers and enablers which mapped to 11 TDF domains. Lack of knowledge of available SMS was a prominent barrier, as well as inaccessible services due to timing and place of delivery. Lack of confidence and emotional factors including fear were barriers to seeking SMS. Social influences shaped knowledge, attitudes and readiness to access SMS. Perceptions of SMS service goals and if in alignment with self-identity, intentions and goals also shaped decisions around accessing support. CONCLUSIONS: While lack of knowledge and provider signposting were common barriers, findings suggest that other psychosocial and emotional factors may be barriers, even if SMS services are accessible. Findings are relevant for oncology healthcare services developing strategies to increase reach of SMS for those living with and beyond cancer.

Cadmium tolerance in tomato: determination of organ-specific contribution by diallel analysis using reciprocal grafts.

Given the increasing problems of water and soil contamination with cadmium (Cd), it is necessary to investigate the genetic and physiological mechanisms of tolerance to this metal in different crops, which can be used for the development of effective crop management strategies. This study aimed to assess the potential of grafting as a strategy to increase Cd tolerance and reduce absorption in tomato by evaluating the contribution of the root system and aerial parts for tolerance mechanisms. To this end, reciprocal grafting and diallel analyses were used to examine the combining ability of contrasting tomato genotypes under exposure to 0 and 35 µM CdCl2. Roots and above-ground parts were found to have specific mechanisms of Cd tolerance, absorption, and accumulation. Grafting of the USP15 genotype (scion) on USP16 (rootstock) provided the greatest synergism, increasing the tolerance index and reducing the translocation index and Cd accumulation in leaves. USP163 exhibited potential for breeding programs that target genotypes with high Cd tolerance. In tomato, both Cd tolerance and accumulation in aerial parts are genotype- and tissue-specific, controlled by a complex system of complementary mechanisms that need to be better understood to support the development of strategies to reduce Cd contamination in aerial parts.

Understanding how self-management education and support programmes for type 2 diabetes are expected to change behaviour: A document analysis of two programmes.

AIMS: Attendance at diabetes self-management education and support (DSMES) programmes for type 2 diabetes is associated with positive outcomes, but the impact on some outcomes is inconsistent and tends to decline over time. Understanding the active ingredients of effective programmes is essential to optimise their effectiveness. This study aimed to (1) retrospectively identify behaviour change techniques (BCTs), mechanisms of action (MoAs) and intervention functions in two DSMES programmes, the Community-Oriented Diabetes Education and the Diabetes Education and Self-Management for Ongoing and Newly Diagnosed and (2) examine variation in content between programmes. METHODS: A multiple case study approach, including a documentary analysis of the programme materials, was conducted. Materials were coded using the BCT Taxonomy v1, the Mode of Delivery Ontology v1 and the Intervention Source Ontology v1. The Behaviour Change Wheel guidance and the Theory and Techniques tool were used to identify intervention functions and MoAs. Programme stakeholders provided feedback on the findings. RESULTS: Thirty-four BCTs were identified across the programmes, with 22 common to both. The identified BCTs were frequently related to 'goals and planning', 'feedback and monitoring' and 'natural consequences'. BCTs were linked with 15 MoAs, predominantly related to reflective motivation ('beliefs about capabilities' and 'beliefs about consequences') and psychological capability ('knowledge'). BCTs served six intervention functions, most frequently 'education', 'enablement' and 'persuasion'. CONCLUSIONS: Although both programmes included several BCTs, some BCTs were rarely or never used. Additional BCTs could be considered to potentially enhance effectiveness by addressing a wider range of barriers.

Systematic documentation of the introduction of COVID-19 vaccines in Latin America and the Caribbean / Documentación sistemática de la introducción de vacunas contra la COVID-19 en América Latina y el Caribe / Documentação sistemática da introdução das vacinas contra a COVID-19 na América Latina e no Caribe

ABSTRACT Objective. To document the process of introducing COVID-19 vaccines in a selection of Latin American and Caribbean countries, including the lessons learned and the strengths and weaknesses, and similarities and differences among programs. Methods. This descriptive study is based on a systematic evaluation of the process of introducing COVID-19 vaccines in Argentina, Belize, Brazil, Costa Rica, Panama and Peru. Data were collected through a questionnaire distributed to key stakeholders. Six informants from each of the included countries participated in this study. The period of the study was from December 2021 through September 2022. Results. The main strengths reported by countries were health workers' commitment to delivering vaccinations, evidence-based decision-making, the development of plans for vaccine introduction, the participation of national immunization technical advisory groups, the availability of economic resources and positive actions from the respective Ministry of Health. The main challenges were the actions of antivaccination groups, problems with electronic immunization registries, a lack of vaccines, delays in the delivery of vaccines and the scarcity of health personnel at the local level. Conclusions. Commitment, the participation of multiple sectors, the availability of resources and preparedness planning were some of the many strengths shown by countries introducing COVID-19 vaccines. Weaknesses included third parties' interests, the lack of information systems and difficulty in accessing vaccines and vaccine services. There is a window of opportunity for countries to maintain the good practices that allowed for the processes' strengths and to assess the identified weaknesses to invigorate immunization programs and prepare for future health crises.

RESUMEN Objetivo. Documentar el proceso de introducción de las vacunas contra la COVID-19 en un algunos países de América Latina y el Caribe, incluidas las enseñanzas extraídas y sus puntos fuertes y débiles, así como las similitudes y diferencias entre los distintos programas. Métodos. Este estudio descriptivo se basa en una evaluación sistemática del proceso de introducción de las vacunas contra la COVID-19 en Argentina, Belice, Brasil, Costa Rica, Panamá y Perú. Los datos se recopilaron mediante un cuestionario distribuido a las principales partes interesadas. El estudio contó con la participación de un informante de cada uno de los seis países incluidos. El período de estudio fue de diciembre del 2021 a septiembre del 2022. Resultados. Los países indicaron como puntos fuertes principales el compromiso del personal de atención de salud con la vacunación, la toma de decisiones basada en la evidencia, la formulación de planes para la introducción de las vacunas, la participación de grupos técnicos asesores nacionales sobre inmunización, la disponibilidad de recursos económicos y las medidas favorables adoptadas por respectivos los Ministerios de Salud. Los retos más importantes fueron las acciones de los grupos contrarios a las vacunas, los problemas con los registros electrónicos de vacunación, la falta de vacunas, los retrasos en la entrega de vacunas y la escasez de personal de atención de salud a nivel local. Conclusiones. Se observó que el compromiso, la participación de múltiples sectores, la disponibilidad de recursos y la planificación de la preparación eran algunos de los puntos fuertes de los países que introdujeron las vacunas contra la COVID-19. Los puntos débiles fueron los intereses de terceros, la falta de sistemas de información y las dificultades para acceder a las vacunas y a los servicios de vacunación. Los países disponen ahora de una oportunidad para mantener las buenas prácticas que propiciaron los puntos fuertes de los procesos y evaluar los puntos débiles identificados a fin de fortalecer los programas de inmunización y prepararse para futuras crisis de salud.

RESUMO Objetivo. Documentar o processo de introdução da vacina contra a COVID-19 em alguns países da América Latina e do Caribe, incluindo as lições aprendidas e os pontos fortes e fracos, bem como semelhanças e diferenças entre os programas. Métodos. Este estudo descritivo baseia-se em uma avaliação sistemática do processo de introdução das vacinas contra a COVID-19 na Argentina, em Belize, no Brasil, na Costa Rica, no Panamá e no Peru. Os dados foram coletados por meio de um questionário distribuído às principais partes interessadas. Seis informantes de cada um dos países incluídos participaram do estudo, que foi realizado entre dezembro de 2021 e setembro de 2022. Resultados. Os principais pontos fortes relatados pelos países foram o comprometimento dos profissionais de saúde com a vacinação, a tomada de decisões baseadas em evidências, o desenvolvimento de planos para a introdução de vacinas, a participação de grupos técnicos assessores nacionais sobre imunização, a disponibilidade de recursos econômicos e ações positivas dos respectivos ministérios da Saúde. Os principais desafios foram as ações de grupos antivacina, problemas com os registros eletrônicos de imunização, a falta de vacinas, atrasos na entrega das vacinas e a escassez de pessoal de saúde em nível local. Conclusões. O comprometimento, a participação de vários setores, a disponibilidade de recursos e o planejamento de preparação foram alguns dos muitos pontos fortes demonstrados pelos países ao introduzirem as vacinas contra a COVID-19. Entre os pontos fracos estavam os interesses de terceiros, a falta de sistemas de informação e a dificuldade de acesso às vacinas e aos serviços de vacinação. Há uma janela de oportunidade para que os países mantenham as boas práticas que viabilizaram os pontos fortes dos processos e avaliem os pontos fracos identificados a fim de revigorar os programas de imunização e preparar-se para futuras crises sanitárias.

Maternity Dietitians' Perspectives on Delivering Gestational Diabetes Care, and Postpartum Follow-Up in Ireland: A Qualitative Study.

BACKGROUND: Medical nutrition therapy is recognized as the cornerstone to optimal glycemic management of gestational diabetes (GDM) during pregnancy and registered dietitian nutritionists (RDNs) are central to delivery of this, yet data are lacking on their views of the barriers and enablers to performing this role. OBJECTIVE: This qualitative study aimed to explore the perspectives of RDNs providing medical nutrition therapy to people with GDM across the Republic of Ireland. DESIGN: Focus groups and semistructured interviews were conducted with RDNs from maternity settings whose roles included providing dietetics services to people with GDM. PARTICIPANTS AND SETTING: Five focus groups and 2 semistructured interviews were conducted with 16 RDNs from 13 maternity sites, whose roles included medical nutrition therapy to people with GDM, in Ireland in February to March 2021. A topic guide addressing GDM management, postpartum care, and future type 2 diabetes prevention was followed. DATA ANALYSIS: Data from focus groups and interviews were analyzed using reflexive thematic analysis. RESULTS: RDNs collectively viewed their role as central to supporting people with GDM. Three themes were generated: Theme 1-a complex layered role-addressed complexities in dietetics practice. Theme 2 highlighted challenges in providing optimum care with sub themes of huge changes with COVID-19, care is not equal, and no defined postpartum pathway. Theme three reported on framing future health needs through sub themes of the 6-week check is a missed opportunity, people need to understand their risk, and more integrated care and type 2 diabetes prevention is needed. CONCLUSIONS: RDNs recognize the need for continuity of care in pregnancy and postpartum for people diagnosed with GDM. However, perceived disparities in allocation of dietetics services for GDM and an absence of agreed care pathways were seen as barriers to optimum care. Collaboration and communication across primary and secondary care settings are essential and require improvement.

Barriers and enablers to maintaining self-management behaviours after attending a self-management support intervention for type 2 diabetes: a systematic review and qualitative evidence synthesis.

Attendance at type 2 diabetes self-management interventions is associated with improved outcomes. However, difficulties maintaining self-management behaviours attenuate long-term impact. This review aimed to identify and synthesise qualitative research on barriers and enablers to maintaining type 2 diabetes self-management behaviours after attending a self-management intervention. Eight electronic databases were searched to identify relevant peer-reviewed and grey literature studies. Data were synthesised using the best-fit framework synthesis approach guided by the themes and constructs identified by Kwasnicka et al. (2016) on their review of theoretical explanations for behaviour change maintenance. Study methodological limitations and confidence in findings were assessed using an adapted version of the Critical Appraisal Skills Programme (CASP) tool and the GRADE-CERQual approach respectively. Eleven articles reporting on 10 studies were included. Twenty-eight barriers and enablers were coded to the a priori themes. Barriers were commonly coded to the themes self-regulation, resources, and environmental and social influences. Enablers were commonly coded to the themes habits and maintenance motives. Methodological limitations of included studies varied, leading to moderate or low confidence in most findings. Interventions may improve behavioural maintenance by providing post-intervention support, promoting positive behaviour change motives, self-regulation, habit formation, and facilitating access to resources and support.

Metabolic signature biomarkers for predicting the recurrence of urological cancers.

A significant number of patients diagnosed with localized urological cancers experience relapse and disease progression after surgery. Hence, molecular markers for patient risk stratification are needed to improve the current management guidelines. This article critically reviews for the first time, to our knowledge, the promise of metabolomics-based approaches to identify metabolic signatures as candidate prognostic biomarkers to predict recurrences at the time of surgery in prostate cancer (PCa), bladder cancer (BCa), and renal cell carcinoma (RCC). Dysregulations in the levels of several tumoral, circulating, and excreted metabolites have been reported in PCa patients experiencing recurrence within 1.5 to 8 years of follow-up. The combination of these metabolic biomarkers with clinical parameters (e.g., pathological T stage, Gleason score) has shown great potential to improve the predictive ability of PCa recurrence. In contrast, predictive biomarkers of recurrence in BCa and RCC have been poorly explored. Overall, this review highlights the great potential of metabolomics in discovering prognostic biomarkers for a more accurate patient risk stratification in urological cancers.

Chronic Kidney Disease: Underlying Molecular Mechanisms-A Special Issue Overview.

Chronic kidney disease (CKD) is an epidemic health issue that requires global attention [...].

Neutral-to-positive cadmium effects on germination and seedling vigor, with and without seed priming.

This review gathered and analyzed data about (i) the Cd-induced impacts on seed germination and seedling vigor, and (ii) the use of different priming agents to mitigate Cd-induced impacts on the early plant development. Critical evaluation of the obtained data revealed intriguing results. First, seeds of diverse species can endure exposures to Cd. Such endurance is exhibited as maintenance of or even improvement in the seed germination and vigor (up to 15% and 70%, respectively). Second, the main factors influencing seed tolerance to Cd toxicity are related to temporal variations in anatomical, physiological, and/or biochemical features. Third, Cd can trigger diverse transgenerational effects on plants by shaping seed endophytes, by modulating seed provisioning with resources and regulatory elements, and/or by altering seed (epi)genomics. Fourth, different chemical, biological and physical priming agents can mitigate Cd-induced impacts on seeds, sometimes enhancing their performance over the control (reference) values. Overall, this review shows that the impacts of Cd on seed germination and vigor encompass not only negative outcomes but also neutral and positive ones, depending upon the Cd dose, media properties, plant species and genotypes, plant developmental stage and organ, and management approaches. Increasing our understanding of plant tolerance mechanisms against the growing background Cd pollution is relevant to support breeding programs, agricultural practices, and health-environmental policies.

Spontaneous Rupture of Splenic Artery Aneurysm.

Splenic artery aneurysms are rare and usually asymptomatic, with a high risk of mortality once they get ruptured. A case report of a spontaneous rupture of a splenic artery aneurysm in a 65-year-old female is reported. The patient presented in the emergency department with abdominal pain, nausea, and vomiting, followed by syncope. A contrast-enhanced CT scan was performed and showed a splenic artery aneurysm measuring 40 × 35 mm surrounded by a hematoma. The patient was submitted to emergency laparotomy with ligation of the splenic artery, aneurysm resection, and splenectomy. There were no surgical complications, and the patient was discharged home on the fifth postoperative day. A rupture of a splenic aneurysm is a rare condition with a high mortality rate and should be considered a differential diagnosis in a patient with abdominal pain and hemodynamic instability.

A colaboração crítica em um curso de leitura em inglês e em português para alunos com necessidades educacionais intelectuais específicas / Critical collaboration in a reading course in english and portuguese for students with specific intellectual educational needs / Colaboración crítica en un curso de lectura en inglés y en portugués para estudiantes con necesidades educativas intelectuales específicas

Este artigo tem por objetivo discutir como a colaboração crítica impacta as ações de pesquisa de duas professorasorientadoras e de um aluno de Ensino Médio com deficiência intelectual em um curso de leitura em inglês e em português para alunos com necessidades educacionais intelectuais específicas. Os participantes de pesquisa usam a linguagem e colaboram criticamente para discutir sua participação. Nesse enquadre, trabalham juntos, desenvolvem suas funções psicológicas superiores, em outras palavras, sua memória, atenção, volição, pensamentos, emoções e linguagem. Como procedimentos metodológicos, a Pesquisa Crítica de Colaboração propicia aos participantes atuarem de maneira interdependente para se constituir e para transformar o contexto de aprendizagem que compartilham. Como resultados parciais, as análises e interpretações sugerem que os momentos de colaboração crítica organizados por meio da Pesquisa Crítica de Colaboração criam possibilidades para os participantes aprimorarem a memória e a própria volição, assim como contribui para que a Educação inclusiva floresça nos contextos escolares. (AU)

This article aims to discuss how critical collaboration impacts the research actions of two advisors-teachers and a high school student with intellectual disabilities in a course of English and Portuguese reading for students with specific intellectual educational needs. Research participants use language and critically collaborate to discuss participation. In this frame, they work together, developing higher psychological functions, in other words, their memory, attention, volition, thoughts, emotions, and language. In terms of methodological procedures, the Critical Collaborative Research allows participants to act in an interdependent way, thus constituting themselves and transforming the learning context which they share. As partial results, the analyses and interpretations suggest that moments of critical collaboration organized by the frame of Critical Collaborative Research create possibilities for participants improve memory and volition, besides contributing for inclusive Education to flourish in school contexts. (AU)

Este artículo tiene como objetivo discutir cómo la colaboración crítica, impacta las acciones de investigación de los profesores-asesores y un estudiante de secundaria con discapacidad intelectual en un curso de lectura en inglés y portugués para estudiantes con necesidades intelectuales específicas de educación. Los participantes de la investigación usan el lenguaje y colaboran críticamente para discutir su participación. En este marco trabajan en conjunto, desarrollan sus funciones psicológicas superiores, es decir, su memoria, atención, volición, pensamientos, emociones y lenguaje. Como Metodología, la Investigación Colaborativa Crítica permite a los participantes actuar de manera interdependiente para constituirse y transformar el contexto de aprendizaje que comparten. Como resultados parciales, los análisis e interpretaciones sugieren que los momentos de colaboración crítica organizados a través de la Investigación de Colaboración Crítica crean posibilidades para que los participantes mejoren su memoria y su propia voluntad, además de contribuir para el florecimiento de la educación inclusiva en contextos escolares. (AU)

Accuracy of guided dental implant surgery using a fully digital workflow: A case series.

STATEMENT OF PROBLEM: Computer-guided implant surgery facilitated by intraoral scanning may enhance the efficiency of the digital workflow. However, it is necessary to assess technique accuracy to evaluate the accuracy of implant placement. PURPOSE: The purpose of this clinical study was to evaluate the accuracy of a virtual computer-aided design and computer-aided manufacturing (CAD-CAM) static guided surgery technique associated with intraoral scanning in partially edentulous participants by analyzing the overlap among preoperative and postoperative cone beam computed tomography (CBCT) scans, virtual planning, and the guided surgery performed. MATERIAL AND METHODS: Eleven partially edentulous participants underwent CBCT and intraoral scanning (TRIOS3). Data were integrated into a software program (ImplantViewer 3.5) for the virtual planning of implants and 3-dimensional (3D) printing of the prototype CAD-CAM surgical guide. A total of 18 implants were placed using the CAD-CAM static computer-aided implant surgery technique (Strong SW). After 15 days, postoperative CBCT scans were made and 4 variables (angular, coronal, apical, and vertical deviation) were measured to compare the virtually planned implants and the implants placed by analyzing the overlap between preoperative and postoperative of the virtual planning and guided surgery performed using the ImplantViewer 3.5 and Rhino 6 software programs. RESULTS: Deviations were found in all parameters analyzed. The mean angular deviation was 2.68 ±1.62 degrees; mean coronal deviation, 0.82 ±0.44 mm; mean apical deviation, 1.14 ±0.44 mm; and mean vertical deviation, 0.62 ±0.44 mm. CONCLUSIONS: The implants placed using the CAD-CAM static guided surgery technique associated with intraoral scanning in partially edentulous participants exhibited angular and linear deviations when compared with virtual planning implants. However, these deviations were not clinically significant.

Sunitinib versus Pazopanib Dilemma in Renal Cell Carcinoma: New Insights into the In Vitro Metabolic Impact, Efficacy, and Safety.

Sunitinib and pazopanib are tyrosine kinase inhibitors (TKIs) used as first-line therapy for metastatic renal cell carcinoma (RCC). Although these TKIs are associated with similar survival outcomes, some differences have been reported in their safety profiles. In this work, traditional toxicological endpoints (cell viability and growth, oxidative stress, and nuclear morphology) and 1H NMR spectroscopy-based metabolomics analysis were used to provide new insights into the cytotoxicity and metabolic mechanisms underlying sunitinib and pazopanib treatments. Tumoral (Caki-1) and non-tumoral (HK-2) human renal cells were exposed to clinically relevant concentrations of sunitinib (2 µM) or pazopanib (50 µM). Sunitinib showed selectivity for cancer cells, inhibiting proliferation, and inducing apoptotic death of Caki-1 cells, whereas pazopanib had a similar cytotoxic effect in both tumoral and non-tumoral cells. 1H-NMR metabolomics unveiled a higher impact of sunitinib on the levels of intracellular metabolites of Caki-1 cells (seven dysregulated metabolites), suggesting dysregulations on amino acid, glutathione and glycerophospholipid metabolisms. In contrast, pazopanib had a higher impact on the levels of extracellular metabolites of Caki-1 cells (seven dysregulated metabolites in culture medium), unveiling alterations on amino acid and energetic metabolisms. In HK-2 cells, sunitinib caused only a minor increase in intracellular isoleucine levels, whereas pazopanib induced several alterations on the intracellular (three dysregulated metabolites) and extracellular (three dysregulated metabolites) compartments suggesting changes on amino acid, glycerophospholipid, and energy metabolisms. Our results demonstrate that these TKIs elicit distinct cellular and metabolic responses, with sunitinib showing better in vitro efficacy against target RCC cells and lesser nephrotoxic potential than pazopanib.

Pectinases Secretion by Saccharomyces cerevisiae: Optimization in Solid-State Fermentation and Identification by a Shotgun Proteomics Approach.

A sequential design strategy was applied to optimize the secretion of pectinases by a Saccharomyces cerevisiae strain, from Brazilian sugarcane liquor vat, on passion fruit residue flour (PFRF), through solid-state fermentation (SSF). A factorial design was performed to determine the influence variables and two rotational central composite designs were executed. The validated experimental result was of 7.1 U mL-1 using 50% PFRF (w/w), pH 5, 30 °C for 24 h, under static SSF. Polygalacturonase, pectin methyl esterase, pectin-lyase and pectate-lyase activities were 3.5; 0.08; 3.1 and 0.8 U mL-1, respectively. Shotgun proteomics analysis of the crude extract enabled the identification of two pectin-lyases, one pectate-lyase and a glucosidase. The crude enzymatic extract maintained at least 80% of its original activity at pH values and temperatures ranging from 2 to 8 and 30 to 80 °C, respectively, over 60 min incubation. Results revealed that PFRF might be a cost-effective and eco-friendly substrate to produce pectinases. Statistical optimization led to fermentation conditions wherein pectin active proteins predominated. To the extent of our knowledge, this is the first study reporting the synthesis of pectate lyase by S. cerevisiae.