Contrast-enhanced ultrasound imaging detects anatomical and functional changes in rat cervical spine microvasculature with normal aging.

Normal aging is associated with significant deleterious cerebrovascular changes; these have been implicated in disease pathogenesis and increased susceptibility to ischemic injury. While these changes are well documented in the brain, few studies have been conducted in the spinal cord. Here, we utilize specialized contrast-enhanced ultrasound (CEUS) imaging to investigate age-related changes in cervical spinal vascular anatomy and hemodynamics in male Fisher 344 rats, a common strain in aging research. Aged rats (24-26 mo., N=6) exhibited significant tortuosity in the anterior spinal artery and elevated vascular resistance compared to adults (4-6 mo., N=6; tortuosity index 2.20±0.15 vs 4.74±0.45, p<0.05). Baseline blood volume was lower in both larger vessels and the microcirculation in the aged cohort, specifically in white matter (4.44e14±1.37e13 vs 3.66e14±2.64e13 CEUS bolus AUC, p<0.05). To elucidate functional differences, animals were exposed to a hypoxia challenge; whereas adult rats exhibited significant functional hyperemia in both gray and white matter (GM: 1.13±0.10-fold change from normoxia, p<0.05; WM: 1.16±0.13, p<0.05), aged rats showed no response. Immunohistochemistry revealed reduced pericyte coverage and activated microglia behavior in aged rats, which may partially explain the lack of vascular response. This study provides the first in vivo description of age-related hemodynamic differences in the cervical spinal cord.

Mutational Dynamics Related to Antibiotic Resistance in M. tuberculosis Isolates from Serial Samples of Patients with Tuberculosis and Type 2 Diabetes Mellitus.

Genetic variation in tuberculosis is influenced by the host environment, patients with comorbidity, and tuberculosis-type 2 diabetes mellitus (TB-T2DM) and implies a higher risk of treatment failure and development of drug resistance. Considering the above, this study aimed to evaluate the influence of T2DM on the dynamic of polymorphisms related to antibiotic resistance in TB. Fifty individuals with TB-T2DM and TB were initially characterized, and serial isolates of 29 of these individuals were recovered on day 0 (diagnosis), 30, and 60. Genomes were sequenced, variants related to phylogeny and drug resistance analyzed, and mutation rates calculated and compared between groups. Lineage X was predominant. At day 0 (collection), almost all isolates from the TB group were sensitive, apart from four isolates from the TB-T2DM group showing the mutation katG S315T, from which one isolate had the mutations rpoB S450L, gyrA A90G, and gyrA D94G. This pattern was observed in a second isolate at day 30. The results provide a first overview of the dynamics of mutations in resistance genes from individuals with TB-T2DM, describing an early development of resistance to isoniazid and a rapid evolution of resistance to other drugs. Although preliminary, these results help to explain the increased risk of drug resistance in individuals with TB and T2DM.

Neurodevelopmental assessment of normocephalic children born to Zika virus exposed and unexposed pregnant people.

BACKGROUND: Studies examining the association between in utero Zika virus (ZIKV) exposure and child neurodevelopmental outcomes have produced varied results. METHODS: We aimed to assess neurodevelopmental outcomes among normocephalic children born from pregnant people enrolled in the Zika in Pregnancy in Honduras (ZIPH) cohort study, July-December 2016. Enrollment occurred during the first prenatal visit. Exposure was defined as prenatal ZIKV IgM and/or ZIKV RNA result at enrollment. Normocephalic children, >6 months old, were selected for longitudinal follow-up using the Bayley Scales of Infant and Toddler Development (BSID-III) and the Ages & Stages Questionnaires: Social-Emotional (ASQ:SE-2). RESULTS: One hundred fifty-two children were assessed; after exclusion, 60 were exposed and 72 were unexposed to ZIKV during pregnancy. Twenty children in the exposed group and 21 children in the unexposed group had a composite score <85 in any of the BSID-III domains. Although exposed children had lower cognitive and language scores, differences were not statistically significant. For ASQ:SE-2 assessment, there were not statistically significant differences between groups. CONCLUSIONS: This study found no statistically significant differences in the neurodevelopment of normocephalic children between in utero ZIKV exposed and unexposed. Nevertheless, long-term monitoring of children with in utero ZIKV exposure is warranted. IMPACT: This study found no statistically significant differences in the neurodevelopment in normocephalic children with in utero Zika virus exposure compared to unexposed children, although the exposed group showed lower cognitive and language scores that persisted after adjustment by maternal age and education and after excluding children born preterm and low birth weight from the analysis. Children with prenatal Zika virus exposure, including those normocephalic and have no evidence of abnormalities at birth, should be monitored for neurodevelopmental delays. Follow-up is important to be able to detect developmental abnormalities that might not be detected earlier in life.

Garlic prevents the oxidizing and inflammatory effects of sepsis induced by bacterial lipopolysaccharide at the systemic and aortic level in the rat. Role of trpv1.

Garlic (Allium sativum) possesses healing properties for diseases like systemic arterial hypertension, cancer and diabetes, among others. Its main component, allicin, binds to the Transient Receptor Potential Vanilloid Type 1 (TRPV1). In this study, we investigated TRPV1's involvement in the regulation of various molecules at the systemic and aortic levels in Wistar rats treated with bacterial lipopolysaccharide (LPS) and garlic to activate the receptor. The experimental groups were as follows: 1) Control, 2) LPS, 3) Garlic, and 4) LPS + Garlic. Using Uv-visible spectrophotometry and capillary zone electrophoresis, we measured the levels of nitric oxide (NO), biopterins BH2 and BH4, total antioxidant capacity (TAC) and oxidizing capacity (OXCA). We also analyzed molecules related to vascular homeostasis such as angiotensin Ang 1-7 and Ang II, as well as endothelin ET-1. In addition, we assessed the inflammatory response by determining the levels of interleukin-6 (IL-6), tumor necrosis factor alpha (TNFα), and galectin-3 (GTN-3). For cell damage assessment, we measured levels of malondialdehyde (MDA), malonate (MTO) and 8-hydroxy-2-deoxyguanosine (8HO2dG). The results showed that LPS influenced the NO pathway at both systemic and aortic levels by increasing OXCA and reducing TAC. It also disrupted vascular homeostasis by increasing Ang-II and ET-1, while decreasing Ang1-7 levels. IL-6, TNFα, GTN-3, as well as MDA, MTO, and 8HO2dG were significantly elevated compared to the control group. The expression of iNOS was increased, but TRPV1 remained unaffected by LPS. However, garlic treatment effectively mitigated the effects of LPS and significantly increased TRPV1 expression. Furthermore, LPS caused a significant decrease in calcitonin gene-related peptide (CGRP) in the aorta, which was counteracted by garlic treatment. Overall, TRPV1 appears to play a crucial role in regulating oxidative stress and the molecules involved in damage and inflammation induced by LPS. Thus, studying TRPV1, CGRP, and allicin may offer a potential strategy for mitigating inflammatory and oxidative stress in sepsis.

Pielonefritis xantogranulomatosa: un reto actual para la laparoscopia.

OBJECTIVE: To present the results of our case series on laparoscopic nephrectomy in xanthogranulomatous pyelonephritis (XGP). METHODS: A retrospective study was conducted that included 143 patients treated with laparoscopic nephrectomy for non-functioning kidney, of whom 15 had XGP, within the time frame of 2011 to 2019. The demographic and clinical data were collected, along with the intraoperative results, complications, and days of hospital stay. RESULTS: Transperitoneal laparoscopic nephrectomy was successfully performed on 15 patients with XGP, with no need for conversion. Mean intraoperative time was 124.4 minutes (range 70-240) and intraoperative blood loss was 148.5 ml (range 30-550), with no blood transfusion required. No intraoperative complications occurred but there was one postoperative complication (6.6%), classified as Clavien-Dindo I (surgical wound infection). Mean hospital stay was 2.85 days (range 2-7). CONCLUSIONS: Nephrectomy is the definitive management for XGP, and the laparoscopic approach should be considered a treatment modality, despite the fact that the pathology involves a severe chronic inflammatory process. Its benefits are reduced surgery duration, less blood loss, a lower complication rate, and fewer days of hospital stay, when performed by a skilled and experienced surgeon.

OBJETIVO: Presentar los resultados de nuestra serie de nefrectomía laparoscópica en pielonefritis xantogranulomatosa (PXG). MÉTODO: Se realizó un estudio retrospectivo que incluyó 143 pacientes tratados con nefrectomía laparoscópica por exclusión renal, de los cuales 15 fueron por PXG, en el periodo comprendido de 2011 a 2019. Se recolectaron datos demográficos y clínicos, resultados transoperatorios, complicaciones y días de estancia hospitalaria. RESULTADOS: Se realizó nefrectomía laparoscópica transperitoneal de forma exitosa en 15 pacientes con PXG, sin necesidad de conversión. El tiempo transoperatorio promedio fue de 124.4 minutos (rango: 70-240). El sangrado transoperatorio fue de 148.5 ml (rango: 30-550), sin requerimiento de transfusión sanguínea. No se reportaron complicaciones transoperatorias; se presentó una complicación en el posoperatorio (6.6%) clasificada como Clavien-Dindo I (infección de la herida quirúrgica). La estancia hospitalaria promedio fue de 2.85 días (rango: 2-7). CONCLUSIONES: El manejo definitivo de la PXG es la nefrectomía, y el abordaje laparoscópico debe ser considerado como una modalidad de tratamiento a pesar de ser una patología que presenta un proceso inflamatorio grave y crónico, obteniéndose beneficios como disminución en el tiempo quirúrgico, menor sangrado, menor tasa de complicaciones y menos días de estancia hospitalaria cuando es realizado por un cirujano experimentado.

Escalas para valoración del dolor neonatal: Una revisión integrativa

Introducción: Debido a que los niños en la etapa de desarrollo preverbal no pueden expresar sus sentimientos, las escalas para valorar el dolor en neonatos son una buena herramienta para uso en la práctica clínica por el profesional de enfermería. Objetivo: Describir las escalas válidas y confiables que se utilizan en la práctica de enfermería para evaluar el dolor en neonatos. Materiales y métodos: Se realizó una revisión integrativa de literatura durante los años 2019 a 2020 de artículos publicados desde el año 1990. Las bases de datos consultadas fueron: PubMed, Lilacs, Proquest, Science Direct, Embase, BVS, Scopus y el metabuscador Google académico. Se analizaron 22 artículos que cumplieron con los criterios de inclusión para su respectivo análisis. Resultados: Se encontraron instrumentos unidimensionales y multidimensionales para la evaluación del dolor agudo y prolongado en recién nacidos prematuros y a término. Discusión: Esta revisión integrativa proporciona a los profesionales de salud, y en especial al profesional de enfermería bases conceptuales para la implementación de herramientas de evaluación clínica del dolor, según la edad gestacional, la duración del dolor y el tipo de indicador. Conclusiones: De acuerdo al conocimiento y características de las escalas, no se puede establecer claramente la más adecuada para uso general o patrón de oro, la selección dependerá de diferentes criterios, como tipo de estímulo, la edad gestacional, y del contexto en el que se encuentra el recién nacido.

Introduction: Since infants are not able to express their feelings during the preverbal stage of development, neonatal pain rating scales are good tools for nurses to use in clinical practice. Objective: To describe valid and reliable scales used in nursing practice to assess neonatal pain. Materials and Methods: An integrative review of articles published since 1990 was conducted from 2019 to 2020. The databases consulted were PubMed, Lilacs, ProQuest, ScienceDirect, Embase, VHL, Scopus, and Google Scholar metasearch engine. Twenty-two articles that met the inclusion criteria were analyzed. Results: Unidimensional and multidimensional instruments were found for assessing acute and prolonged pain in preterm and term neonates. Discussion: This integrative review provides healthcare professionals, especially nurses, with a conceptual basis for implementing clinical pain assessment tools according to gestational age, duration of pain, and type of indicator. Conclusions: According to the knowledge and characteristics of the scales, it is not possible to clearly establish the most appropriate one for general use or a gold standard; the selection will depend on different criteria, such as the type of stimulus, gestational age, and the newborn's context.

Introdujo: Como as crianzas na fase pré-verbal do desenvolvimento nao conseguem expressar seus sentimentos, as escalas de avaliagáo da dor em neonatos sao uma boa ferramenta para uso na prática clínica pelos profissionais de enfermagem. Objetivo: Descrever as escalas válidas e confiáveis utilizadas na prática de enfermagem para avaliar a dor em neonatos. Materiais e Métodos: Foi realizada uma revisao integrativa da literatura durante os anos de 2019 a 2020 de artigos publicados desde 1990. As bases de dados consultadas foram: PubMed, Lilacs, Proquest, Science Direct, Embase , BVS, Scopus e o metabuscador académico Google. Foram analisados 22 artigos que atenderam aos critérios de inclusao para sua respectiva análise. Resultados: Foram encontrados instrumentos unidimensionais e multidimensionais para avaliagáo da dor aguda e prolongada em recém-nascidos pré-termo e a termo. Discussao: Esta revisáo integrativa fornece aos profissionais de saúde, e especialmente aos profissionais de enfermagem, bases conceituais para a implementagáo de instrumentos de avaliagáo clínica da dor, de acordo com a idade gestacional, duragáo da dor e tipo de indicador. Condusdes: De acordo com o conhecimento e as características das escalas, náo é possível estabelecer claramente a mais adequada para uso geral ou padráo-ouro, a selegáo dependerá de diferentes critérios, como tipo de estímulo, idade gestacional e contexto em que é usado. o recém-nascido é encontrado.

Development of a new generation of miniemulsion based on cottonseed oil with α-tocopherol and ZnO and evaluation of its adjuvant activity.

Background: Emulsions have been widely used as immunological adjuvants. But the use of materials derived from plants such as cottonseed oil, alpha-tocopherol, or minerals such as zinc, as well as their use at the nanometric scale has been little explored. In this study, we develop a new miniemulsion and evaluated its antioxidant and phagocytic capacity, as well as parameters related to immune response stimulation by cytokine expression and antibodies production in a mice model. Methods: Formulated CN (cottonseed oil miniemulsion) and CNZ (cottonseed oil miniemulsion whit zinc oxide nanoparticles) miniemulsions were characterized by scanning electronic microscopy SEM, DLS and FT-IR. In murine macrophages, splenocytes and thymocytes primary cultures safety and cytotoxicity were determined by MTT. In macrophages the antioxidant and phagocytic capacity was evaluated. In BALB/c mice, the stimulation of the immune system was determined by the expression of cytokines and the production of antibodies. Results: The CN and CNZ presented stability for 90 days. Immediately after preparation, the CN presented a higher particle size (543.1 nm) than CNZ (320 nm). FT-IR demonstrated the correct nanoparticle synthesis by the absence of sulfate groups. CN and CNZ (1.25 to 10 µL/mL) had no toxic effect on macrophages (p = 0.108), splenocytes (p = 0.413), and thymocytes (p = 0.923). All CN and CNZ doses tested induced nitric oxide and antioxidants production in dose dependent manner when compared with control. CN-ovalbumin and CNZ-ovalbumin treatments in femoral subcutaneous tissue area showed inflammation with higher leukocyte infiltration compared with FCA. The intraperitoneal administration with CN, CNZ, and FCA showed a higher total intraperitoneal cells recruitment (CD14+) after 24 h of inoculation than control (p = 0.0001). CN and CNZ increased the phagocyte capacity with respect to untreated macrophages in the Candida albicans-phagocytosis assay. The evaluation of residual CFU indicated that only CN significantly decreased (p = 0.004) this value at 3 h. By other side, only CN increased (p = 0.002) the nitric oxide production. CNZ stimulated a major INFγ secretion compared with FCA at day 7. A major IL-2 secretion was observed at days 7 and 14, stimulated with CN and CNZ. Both miniemulsions did not affect the antibody isotypes production (IgG1, IgG2a, IgG3, IgA and IgM) at days 7, 14, 28, and 42. CN induced a significant IgG production against OVA, but lesser than FCA. Conclusions: The two new miniemulsions with adjuvant and antioxidant capacity, were capable of generating leukocyte infiltration and increased cytokines and antibodies production.

Un profesor clínico y pedagogo en el Aprendizaje Basado en Problemas / A clinician and pedagogy professor for problem-based learning

Introducción: Las cualificaciones requeridas a un profesor tienen implicaciones en la vinculación laboral, el desarrollo profesoral y la calidad de la formación del recurso humano en salud. Objetivo: Determinar la experticia de un profesor y si existe evidencia empírica de que sus antecedentes en Aprendizaje Basado en Problemas influyan en el aprendizaje de los estudiantes. Métodos: En esta revisión de alcance se buscaron artículos publicados en las bases de datos Medline, Scopus, PubMmed, Google Scholar, EBSCO y ScienceDirect. La búsqueda incluyó, inicialmente, artículos publicados entre 2015 y 2020; luego, se incluyeron los estudios citados en estos artículos para aumentar el número de la muestra. La evaluación fue realizada de manera independiente por dos investigadores. En total, 11 artículos cumplían con los criterios de inclusión. Se extrajeron y analizaron datos sobre las cualidades del profesor del ABP. Resultados: Los estudios que exploran las cualificaciones del docente del Aprendizaje Basado en Problemas son escasos y no existe un criterio unificado sobre la formación y la experiencia requeridas a ellos. Las evidencias empíricas encontradas son cuestionables y muestran vacíos en la comprensión de este problema, aunque sugieren como mejor opción a un profesor experto en medicina y pedagogía. Conclusiones: Estos hallazgos representan un serio defecto del Aprendizaje Basado en Problemas. Una posible solución es integrar la enseñanza de la pedagogía a los currículos médicos para contar con una mayor cantidad de profesores expertos tanto en medicina como en docencia(U)

Introduction: The qualifications required from a professor have implications for job placement, professional development and the quality of health human resource training. Objective: To determine a professor's expertise and whether there is empirical evidence that his or her background in problem-based learning (PBL) influences student learning. Methods: In this scoping review, published articles were searched for in the Medline, Scopus, PubMed, Google Scholar, EBSCO and ScienceDirect databases. The search initially included articles published between 2015 and 2020; then, studies cited in these articles were included to increase the sample number. The assessment was performed independently by two researchers. A sheer number of eleven articles met the inclusion criteria. Data about the qualities of the PBL professor were extracted and analyzed. Results: Studies exploring the qualifications of the PBL professor are scarce, while there is no unified criterion on the training and experience required from them. The empirical evidence found is questionable and shows gaps in the understanding of this problem, although it suggests a professor with expertise in medicine and pedagogy as the best option. Conclusions: These findings represent a serious shortcoming of PBL. A possible solution is to integrate the teaching of pedagogy into medical curricula in order to have a greater number of professors with expertise in both medicine and teaching(AU)

Modularization in Belief-Desire-Intention agent programming and artifact-based environments.

This article proposes an extension for the Agents and Artifacts meta-model to enable modularization. We adopt the Belief-Desire-Intention (BDI) model of agency to represent independent and reusable units of code by means of modules. The key idea behind our proposal is to take advantage of the syntactic notion of namespace, i.e., a unique symbol identifier to organize a set of programming elements. On this basis, agents can decide in BDI terms which beliefs, goals, events, percepts and actions will be independently handled by a particular module. The practical feasibility of this approach is demonstrated by developing an auction scenario, where source code enhances scores of coupling, cohesion and complexity metrics, when compared against a non-modular version of the scenario. Our solution allows to address the name-collision issue, provides a use interface for modules that follows the information hiding principle, and promotes software engineering principles related to modularization such as reusability, extensibility and maintainability. Differently from others, our solution allows to encapsulate environment components into modules as it remains independent from a particular BDI agent-oriented programming language.

Escalas para valoración del dolor neonatal: Una revisión integrativa / Neonatal pain assessment scales: An integrative review

Introducción: Debido a que los niños en la etapa de desarrollo preverbal no pueden expresar sus sentimientos, las escalas para valorar el dolor en neonatos son una buena herramienta para uso en la práctica clínica por el profesional de enfermería. Objetivo: Describir las escalas válidas y confiables que se utilizan en la práctica de enfermería para evaluar el dolor en neonatos. Materiales y métodos: Se realizó una revisión integrativa de literatura durante los años 2019 a 2020 de artículos publicados desde el año 1990. Las bases de datos consultadas fueron: PubMed, Lilacs, Proquest, Science Direct, Embase, BVS, Scopus y el metabuscador Google académico. Se analizaron 22 artículos que cumplieron con los criterios de inclusión para su respectivo análisis. Resultados: Se encontraron instrumentos unidimensionales y multidimensionales para la evaluación del dolor agudo y prolongado en recién nacidos prematuros y a término. Discusión: Esta revisión integrativa proporciona a los profesionales de salud, y en especial al profesional de enfermería bases conceptuales para la implementación de herramientas de evaluación clínica del dolor, según la edad gestacional, la duración del dolor y el tipo de indicador. Conclusiones: De acuerdo al conocimiento y características de las escalas, no se puede establecer claramente la más adecuada para uso general o patrón de oro, la selección dependerá de diferentes criterios, como tipo de estímulo, la edad gestacional, y del contexto en el que se encuentra el recién nacido

Introduction: Since infants are not able to express their feelings during the preverbal stage of development, neonatal pain rating scales are good tools for nurses to use in clinical practice. Objective: To describe valid and reliable scales used in nursing practice to assess neonatal pain. Materials and Methods: An integrative review of articles published since 1990 was conducted from 2019 to 2020. The databases consulted were PubMed, Lilacs, ProQuest, ScienceDirect, Embase, VHL, Scopus, and Google Scholar metasearch engine. Twenty-two articles that met the inclusion criteria were analyzed. Results: Unidimensional and multidimensional instruments were found for assessing acute and prolonged pain in preterm and term neonates. Discussion: This integrative review provides healthcare professionals, especially nurses, with a conceptual basis for implementing clinical pain assessment tools according to gestational age, duration of pain, and type of indicator. Conclusions: According to the knowledge and characteristics of the scales, it is not possible to clearly establish the most appropriate one for general use or a gold standard; the selection will depend on different criteria, such as the type of stimulus, gestational age, and the newborn's context.

Introdução: Como as crianças na fase pré-verbal do desenvolvimento não conseguem expressar seus sentimentos, as escalas de avaliação da dor em neonatos são uma boa ferramenta para uso na prática clínica pelos profissionais de enfermagem. Objetivo: Descrever as escalas válidas e confiáveis utilizadas na prática de enfermagem para avaliar a dor em neonatos. Materiais e Métodos: Foi realizada uma revisão integrativa da literatura durante os anos de 2019 a 2020 de artigos publicados desde 1990. As bases de dados consultadas foram: PubMed, Lilacs, Proquest, Science Direct, Embase , BVS, Scopus e o metabuscador acadêmico Google. Foram analisados 22 artigos que atenderam aos critérios de inclusão para sua respectiva análise. Resultados: Foram encontrados instrumentos unidimensionais e multidimensionais para avaliação da dor aguda e prolongada em recém-nascidos pré-termo e a termo. Discussão: Esta revisão integrativa fornece aos profissionais de saúde, e especialmente aos profissionais de enfermagem, bases conceituais para a implementação de instrumentos de avaliação clínica da dor, de acordo com a idade gestacional, duração da dor e tipo de indicador. Conclusões: De acordo com o conhecimento e as características das escalas, não é possível estabelecer claramente a mais adequada para uso geral ou padrão-ouro, a seleção dependerá de diferentes critérios, como tipo de estímulo, idade gestacional e contexto em que é usado. o recém-nascido é encontrado.

KRAS Promoter Methylation Status and miR-18a-3p and miR-143 Expression in Patients With Wild-type KRAS Gene in Colorectal Cancer.

BACKGROUND/AIM: Although some mutations of KRAS proto-oncogene, GTPase (KRAS) have been associated with the prognosis and therapeutic management of colorectal cancer (CRC), the epigenetic mechanisms (DNA methylation and microRNA expression) that regulate wild-type KRAS expression in patients with CRC are poorly known. The aim of this study was to establish whether there is a relationship between the expression of the wild-type KRAS gene, the methylation status of its distal promoter, and miR-143 and miR-18a-3p levels in samples of sporadic CRC. PATIENTS AND METHODS: A total of 51 cases of sporadic CRC with wild-type KRAS were analyzed. The expression levels of KRAS mRNA, miR-18a-3p, miR-143, and KRAS protein, as well as methylation in the distal promoter of the KRAS gene were evaluated. RESULTS: In the analyzed cases, KRAS mRNA expression was detected in 51.1%; wild-type KRAS protein was found in the membrane in 31.4% and in the cytoplasm in 98% of cases. An inverse relationship of marginal significance was observed between miR-18a-3p and KRAS protein expression in the cytoplasm (odds ratio=0.14, 95% confidence interval=0.012-1.092; p=0.08). The methylation status of the distal promoter of KRAS at four CpG islands was analyzed in 30 cases (58.8%): partial methylation of the four CpG islands evaluated was observed in two cases (6.7%). In these cases, KRAS protein expression was not evidenced at the membrane level; miR-18a-3p expression was not detected either but high expression of miR-143 was observed. CONCLUSION: No association was found between the expression levels of KRAS mRNA, miR-18a-3p, miR-143 and methylation status. Methylation status was detected with low frequency, thus being the first report of methylation in wild-type KRAS.

Native and fermented waxy cassava starch as a novel gluten-free and clean label ingredient for baking and expanded product development.

Amylose-free and wild-type cassava starches were fermented for up to 30 days and oven- or sun-dried. The specific volume (ν) after baking was measured in native and fermented starches. The average ν (across treatments) for waxy starch was 3.5 times higher than that in wild-type starches (17.6 vs. 4.8 cm3 g-1). The best wild-type starch (obtained after fermentation and sun-drying) had considerably poorer breadmaking potential than native waxy cassava (8.4 vs. 16.4 cm3 g-1, respectively). The best results were generally obtained through the synergistic combination of fermentation (for about 10-14 days) and sun-drying. Fermentation reduced viscosities and the weight average molar mass led to denser macromolecules and increased branching degree, which are linked to a high loaf volume. The absence of amylose, however, was shown to be a main determinant as well. Native waxy starch (neutral in taste, gluten-free, and considerably less expensive than the current alternatives to cassava) could become a new ingredient for the formulation of clean label-baked or fried expanded products.

Key Challenges and Emerging Technologies in Industrial IoT Architectures: A Review.

The Industrial Internet of Things (IIoT) is bringing evolution with remote monitoring, intelligent analytics, and control of industrial processes. However, as the industrial world is currently in its initial stage of adopting full-stack development solutions with IIoT, there is a need to address the arising challenges. In this regard, researchers have proposed IIoT architectures based on different architectural layers and emerging technologies for the end-to-end integration of IIoT systems. In this paper, we review and compare three widely accepted IIoT reference architectures and present a state-of-the-art review of conceptual and experimental IIoT architectures from the literature. We identified scalability, interoperability, security, privacy, reliability, and low latency as the main IIoT architectural requirements and detailed how the current architectures address these challenges by using emerging technologies such as edge/fog computing, blockchain, SDN, 5G, Machine Learning, and Wireless Sensor Networks (WSN). Finally, we discuss the relation between the current challenges and emergent technologies and present some opportunities and directions for future research work.

Whole genome sequencing analysis to evaluate the influence of T2DM on polymorphisms associated with drug resistance in M. tuberculosis.

BACKGROUND: Type 2 diabetes mellitus (T2DM) has been associated with treatment failure, and the development of drug resistance in tuberculosis (TB). Also, whole-genome sequencing has provided a better understanding and allowed the growth of knowledge about polymorphisms in genes associated with drug resistance. Considering the above, this study analyzes genome sequences to evaluate the influence of type 2 diabetes mellitus in the development of mutations related to tuberculosis drug resistance. M. tuberculosis isolates from individuals with (n = 74), and without (n = 74) type 2 diabetes mellitus was recovered from online repositories, and further analyzed. RESULTS: The results showed the presence of 431 SNPs with similar proportions between diabetics, and non-diabetics individuals (48% vs. 52%), but with no significant relationship. A greater number of mutations associated with rifampicin resistance was observed in the T2DM-TB individuals (23.2% vs. 16%), and the exclusive presence of rpoBQ432L, rpoBQ432P, rpoBS441L, and rpoBH445L variants. While these variants are not private to T2DM-TB cases they are globally rare highlighting a potential role of T2DM. The phylogenetic analysis showed 12 sublineages, being 4.1.1.3, and 4.1.2.1 the most prevalent in T2DM-TB individuals but not differing from those most prevalent in their geographic location. Four clonal complexes were found, however, no significant relationship with T2DM was observed. Samples size and potential sampling biases prevented us to look for significant associations. CONCLUSIONS: The occurrence of globally rare rifampicin variants identified only in isolates from individuals with T2DM could be due to the hyperglycemic environment within the host. Therefore, further studies about the dynamics of SNPs' generation associated with antibiotic resistance in patients with diabetes mellitus are necessary.

Thermal Debridement in the Management of Low Grade Scapholunate Ligament Tears.

Low grade scapholunate interosseous ligament (SLIL) tears are often managed with mechanical or thermal arthroscopic debridement, although this remains controversial. This study aimed to assess the short-term outcomes of thermal debride- ment of low-grade SLIL tears. Patients with low grade SLIL tears who underwent arthroscopic thermal debridement between 2010 and 2017 were identified and divided into two groups: isolated thermal debridement and concomitant pro- cedures. Patient reported outcomes, wrist range of motion, grip strength, return to work, and baseline activities were evaluated. Twenty-seven patients underwent isolated thermal debridement and 20 underwent concomitant procedures. Pain significantly improved in both groups. Grip strength significantly improved in the concomitant procedure group. There was no significant change in wrist range of motion in either group. Most patients returned to baseline activities. Arthroscopic thermal debridement provides good outcomes in patients with low grade SLIL tears both in isolation and in association with other injuries.

SNPs in Genes Related to DNA Damage Repair in Mycobacterium Tuberculosis: Their Association with Type 2 Diabetes Mellitus and Drug Resistance.

Genes related to DNA damage repair in Mycobacterium tuberculosis are critical for survival and genomic diversification. The aim of this study is to compare the presence of SNPs in genes related to DNA damage repair in sensitive and drug-resistant M. tuberculosis genomes isolated from patients with and without type 2 diabetes mellitus (T2DM). We collected 399 M. tuberculosis L4 genomes from several public repositories; 224 genomes belonging to hosts without T2DM, of which 123 (54.9%) had drug sensitive tuberculosis (TB) and 101 (45.1%) had drug resistance (DR)-TB; and 175 genomes from individuals with T2DM, of which 100 (57.1%) had drug sensitive TB and 75 (42.9%) had DR-TB. The presence of SNPs in the coding regions of 65 genes related to DNA damage repair was analyzed and compared with the resistance profile and the presence/absence of T2DM in the host. The results show the phylogenetic relationships of some SNPS and L4 sub-lineages, as well as differences in the distribution of SNPs present in DNA damage repair-related genes related to the resistance profile of the infecting strain and the presence of T2DM in the host. Given these differences, it was possible to generate two discriminant functions to distinguish between drug sensitive and drug resistant genomes, as well as patients with or without T2DM.

Dry but Not Humid Thermal Processing of Aloe vera Gel Promotes Cytotoxicity on Human Intestinal Cells HT-29.

Aloe vera products, both in food and cosmetics, are becoming increasingly popular due to their claimed beneficial effects, which are mainly attributed to the active compound acemannan. Usually, these end products are based on powdered starting materials. High temperatures during the drying process to obtain the starting materials have several advantages, like shortening the drying time, eliminating toxic aloin and reducing bacterial contamination. Nevertheless, there are two major drawbacks: first, at temperatures of 80 °C or higher, structural changes in acemannan, especially its deacetylation (>46%), are triggered, which does not happen at lower temperatures (14% at 60 °C); secondly, a toxic principle is formed at higher temperatures, resulting in a higher cytotoxicity. Thus, two temperature-dependent but opposing effects cause with a median cytotoxic concentration of CC50 = 0.4× a peak of cytotoxicity at 80 °C; at 60 °C this cytotoxic substance is not formed and at 100 °C aloin is more readily eliminated, resulting in a CC50 = 1.1× and CC50 = 1.4×, respectively. The cytotoxic substance generated by dry heat at 80 °C is not a modified polysaccharide because its polysaccharide-enriched alcohol-insoluble fraction is with CC50 = 0.9× less cytotoxic. Moreover, this substance is polar enough to be washed away with ethanol. Additionally, when Aloe gel is heated at 80 °C under humid conditions (pasteurization), the cytotoxicity does not increase (CC50 = 1.6×). Finally, to produce powdered starting materials from Aloe gel, it is recommended to use temperatures of around 60 °C in order to preserve the acemannan structure (and thus biological activity) and the low cytotoxicity.

Impact of the Dopant Species on the Thermomechanical Material Properties of Thermoelectric Mg2Si0.3Sn0.7.

Thermoelectric generators are an excellent option for waste heat reuse. Materials for such devices have seen their thermoelectric properties improving constantly. The functioning of a generator, however, does not only depend on thermoelectric properties. Thermal and mechanical properties play a decisive role in the feasibility of any thermoelectric generator. To shed light on the properties exhibited by thermoelectric materials, we present the temperature dependent characterization of Young's modulus and coefficient of thermal expansion for Mg2Si0.3Sn0.7. Comparing undoped to Bi-doped n-type and Li-doped p-type material, we investigated the influence of doping in the relevant temperature regime and found the influences to be minor, proving similar properties for n- and p-type. We found a Young's modulus of 84 GPa for the p-type and 83 GPa for the n-type, similar to that of the undoped compound with 85 GPa. The thermal expansion coefficients of undoped, as well as n- and p-type were equally similar with values ranging from 16.5 to 17.5 × 10-6 1/K. A phase analysis was performed to further compare the two materials, finding a similar phase distribution and microstructure. Finally, using the gathered data, estimations on the possible thermally induced stresses under a temperature difference are provided to evaluate the relevance of knowing temperature dependent thermal and mechanical properties.

TRPV1 Contributes to Modulate the Nitric Oxide Pathway and Oxidative Stress in the Isolated and Perfused Rat Heart during Ischemia and Reperfusion.

The transient vanilloid receptor potential type 1 (TRPV1) regulates neuronal and vascular functions mediated by nitric oxide (NO) and by the calcitonin gene-related peptide (CGRP). Here, we study the participation of TRPV1 in the regulation of myocardial injury caused by ischemia-reperfusion and in the control of NO, tetrahydrobiopterin (BH4), the cGMP pathway, CGRP, total antioxidant capacity (TAC), malondialdehyde (MDA) and phosphodiesterase-3 (PDE-3). Isolated hearts of Wistar rats perfused according to the Langendorff technique were used to study the effects of an agonist of TRPV1, capsaicin (CS), an antagonist, capsazepine (CZ), and their combination CZ+CS. The hearts were subjected to three conditions: (1) control, (2) ischemia and (3) ischemia-reperfusion. We determined cardiac mechanical activity and the levels of NO, cGMP, BH4, CGRP, TAC, MDA and PDE-3 in ventricular tissue after administration of CS, CZ and CZ+CS. Western blots were used to study the expressions of eNOS, iNOS and phosphorylated NOS (pNOS). Structural changes were determined by histological evaluation. CS prevented damage caused by ischemia-reperfusion by improving cardiac mechanical activity and elevating the levels of NO, cGMP, BH4, TAC and CGRP. TRPV1 and iNOS expression were increased under ischemic conditions, while eNOS and pNOS were not modified. We conclude that the activation of TRPV1 constitutes a therapeutic possibility to counteract the damage caused by ischemia and reperfusion by regulating the NO pathway through CGRP.

Overcoming Asymmetric Contact Resistances in Al-Contacted Mg2(Si,Sn) Thermoelectric Legs.

Thermoelectric generators are a reliable and environmentally friendly source of electrical energy. A crucial step for their development is the maximization of their efficiency. The efficiency of a TEG is inversely related to its electrical contact resistance, which it is therefore essential to minimize. In this paper, we investigate the contacting of an Al electrode on Mg2(Si,Sn) thermoelectric material and find that samples can show highly asymmetric electrical contact resistivities on both sides of a leg (e.g., 10 µΩ·cm2 and 200 µΩ·cm2). Differential contacting experiments allow one to identify the oxide layer on the Al foil as well as the dicing of the pellets into legs are identified as the main origins of this behavior. In order to avoid any oxidation of the foil, a thin layer of Zn is sputtered after etching the Al surface; this method proves itself effective in keeping the contact resistivities of both interfaces equally low (<10 µΩ·cm2) after dicing. A slight gradient is observed in the n-type leg's Seebeck coefficient after the contacting with the Zn-coated electrode and the role of Zn in this change is confirmed by comparing the experimental results to hybrid-density functional calculations of Zn point defects.