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El objetivo de este estudio fue analizar la capacidad explicativa de la tolerancia al distrés (TD) en la comprensión lectora (CL) de textos narrativos y expositivos, considerando conjuntamente el rol de la memoria de trabajo (MT) en niños de 9 a 12 años de edad. Se evaluaron 211 niños que cursaban cuarto a sexto año de educación primaria. La TD se evaluó mediante el Indicador Comportamental de Resiliencia al Distrés, la MT con una tarea de amplitud compleja de dígitos con interferencia, mientras que la CL de texto narrativo y expositivo con una prueba de screening apropiada a la edad. Los resultados muestran que, al ser consideradas conjuntamente, la MT contribuye al desempeño en CL tanto de textos narrativos como expositivos, mientras que la TD no realiza un aporte significativo. El estudio aporta al conocimiento de factores que contribuyen al desempeño en CL en niños de edad escolar.

Cognitive flexibility refers to the ability to rapidly and accurately switch between tasks. It is regarded as a core dimension of executive functions and has been reported to improve during childhood and into early adulthood. For its evaluation, the task-switching paradigm is widely used. Switching between tasks or response sets imposes a series of costs on performance (i.e., mixing costs, global switch costs, local switch costs). There is less evidence analyzing switching performance in children than in other age groups, and few studies have specifically analyzed switching costs only in school-age children. In the present study, we aimed to analyze age-related changes in task switching in children aged 9-12 years old. We considered year-to-year changes in performance, specifically in response time based mixing costs, global switch costs, and local switch costs. To do this, we used a task switching measure to evaluate 231 children in Argentina, aged 9-12 years (M age = 10.94, SD = 0.88) who were aggregated into four age groups (9, 10, 11, and 12 years old). Results show consistent mixing costs, global switch costs, and local switch costs at each age. However, we did not find age-related differences in the magnitude of such costs. These results suggest that both the ability to maintain and select between two tasks, and to switch from one response set to another could be considered relatively constant during this period.

Recent findings of stem/progenitor cells in maternal milk and their ability to cross the intestinal barrier of lactating newborns and integrate into neonatal organs to promote optimal child development present a new challenge in perinatal medicine. These findings emphasize the need for all mothers to breastfeed their babies for a long time. According to recent research, breastfeeding protects the lactating newborn from multiple infectious agents that can cause severe and fatal early infancy diseases. The second benefit is that maternal stem cells accelerate the development of several organs, including the brain, protecting lactating infants from severe childhood and adult diseases. The success and diffusion of exclusive breastfeeding, especially in low-resource settings, depends on mothers' knowledge of the many benefits for their child, including recent discoveries on breastfeeding's powerful benefits. Every mother may need simple booklets to learn about the unique benefits of maternal breastfeeding, including the nutrients and multiple cell types that protect the newborn from infections and accelerate neonatal organ development. Social media should also be encouraged to spread news about breastfeeding and maternal stem cells' impact on lactating infants' health. Health belief model interventions may boost breastfeeding. In conclusion, the discovery of massive amounts of cells in maternal milk and the identification of stem/progenitors with previously unknown potential in newborn development after birth should be considered a new valuable tool for exclusive breastfeeding advocates. Data here suggests that every action to spread this message and educate mothers and families about breastfeeding's irreplaceable role is mandatory.

En el centro-oeste de Santa Cruz (Patagonia, Argentina) se han desarrollado investigaciones arqueológicas desde hace más de 40 años. Desde sus inicios, el equipo de trabajo estableció vínculos con las comunidades de Perito Moreno, Gobernador Gregores y Lago Posadas y se desarrollaron charlas y talleres con distintos actores sociales de estas localidades. A partir de diversos factores, en los últimos años se sistematizaron las tareas de gestión y extensión. En particular, se han realizado distintas actividades en las localidades mencionadas y en el Área Metropolitana de Buenos Aires, en las que han participado estudiantes y docentes de distintos niveles educativos, autoridades, emprendedores turísticos, representantes de las comunidades originarias y otros pobladores locales. En este artículo, en primer lugar, se resumen las experiencias del equipo de trabajo en relación con la comunicación pública de la ciencia a lo largo de aproximadamente cuatro décadas. En particular se consideran los distintos tipos de actividades llevadas a cabo y los vínculos establecidos con las distintas localidades y los actores sociales participantes. Asimismo, se relaciona esta trayectoria de trabajo con las coyunturas locales y otros aspectos contextuales que incidieron en su desarrollo. Por último, se reflexiona sobre las características de nuestra propia experiencia en la comunicación pública de la ciencia atendiendo a sus alcances y limitaciones.

The aim of this study was to analyze the moderating effect of distress tolerance (DT) on the relationship between executive functions and academic performance (AP). Participants were 270 children aged 9-12 years. Executive functions (EFs)--working memory (WM), inhibition, and cognitive flexibility--and DT were evaluated using computerized tasks. Direct measures of reading comprehension and mathematical calculation, as well as school grades, were used to assess AP. Results showed that verbal WM and cognitive flexibility were positively associated with reading indicators, but to a greater extent among children with medium and low DT. A positive association was found between visuospatial WM, and a mathematical indicator, to a greater extent among children with medium and low DT. The EFs did not show explanatory capacity for AP in children with high DT. These results suggest that DT could function as a "compensatory" resource.

Introduction: Medical quality of life (QoL) is an international object of study. Brazilian Plastic Surgeons QoL hasn`t yet been assessed, with few studies to perform any evaluation on the subject or estimate variables involved. Methods: This is a transversal, non-comparative, non-experimental, contemporary and of full selection study. An on-line research was performed between July and December in 2021, through the WHOQOL-bref questionnaire application, added with social-demographic information. The population will be composed of plastic surgery residents and surgeons associated with the Brazilian Society of Plastic Surgery (SBCP). Results: We obtained 168 answers via Google Forms®, which allowed us to determine our population through social- demographic questionnaire and make associations with the WHOQOL-bref findings. Conclusion: The current study identified correlations between sociodemographics and quality of life of the Brazilian plastic surgeon. We bring forward descriptive data on a subpopulation of responders inside the SBCP, which achieved a score positively higher than 50% in all of the questionnaire domains.

This review summarizes the results of a series of studies performed by our group with the aim to define the expression levels of thymosin β4 and thymosin β10 over time, starting from fetal development to different ages after birth, in different human organs and tissues. The first section describes the proteomics investigations performed on whole saliva from preterm newborns and gingival crevicular fluid, which revealed to us the importance of these acidic peptides and their multiple functions. These findings inspired us to start an in-depth investigation mainly based on immunochemistry to establish the distribution of thymosin β4 and thymosin β10 in different organs from adults and fetuses at different ages (after autopsy), and therefore to obtain suggestions on the functions of β-thymosins in health and disease. The functions of β-thymosins emerging from these studies, for instance, those performed during carcinogenesis, add significant details that could help to resolve the nowadays so-called “β-thymosin enigma”, i.e., the potential molecular role played by these two pleiotropic peptides during human development.

Antecedentes: distintos autores indican que las actitudes hacia las matemáticas, las funciones ejecutivas y el conocimiento matemático previo representan variables centrales en el aprendizaje de esta asignatura; no obstante, no se dispone de evidencia respecto a su contribución conjunta y relativa para la predicción del desempeño en matemáticas en estudiantes de nivel secundario. Objetivo general: analizar la contribución de la competencia percibida, el gusto por las matemáticas, las funciones ejecutivas y el conocimiento previo en la predicción del desempeño en matemáticas en estudiantes de primer y segundo año del nivel secundario. Método: participaron 178 estudiantes de los primeros años de secundaria (edad M = 13.4 años, DE = .32; 45.5% varones). Resultados: se halló que el conjunto de variables explicó el 49% de la varianza en el desempeño en matemáticas, siendo la competencia percibida, el gusto por las matemáticas y la memoria de trabajo predictores significativos. No se hallaron diferencias en la fuerza de la relación de la memoria de trabajo con el desempeño en matemáticas entre los años escolares analizados. Conclusiones: los aspectos actitudinales evaluados y la memoria de trabajo representan variables de importancia para predecir el desempeño en matemáticas en el nivel secundario. Contribución de autoría Todos los autores aportaron en todos los aspectos del trabajo.

Aunque las emociones básicas son consideradas universales, su significado varía según las culturas y los grupos sociales. En el marco de la construcción social de los significados, aquí se analizan y comparan las representaciones semánticas de seis emociones básicas (alegría, tristeza, enojo, miedo, sorpresa, asco) activadas por 78 niños (9 a 11 años) y 78 adultos (20 a 40 años). En base a una tarea de producción de atributos semánticos, se construyó la representación semántica asociada a cada emoción para cada rango etario. Luego, utilizando la metodología provista por el análisis de redes sociales (ARS), se analizó la calidad intrínseca y las diferencias en cantidad y tipos de atributos, estructura de las redes, densidad y nivel de entropía, y el uso de la definición por negación. Los resultados indicaron que los mapas semánticos de niños y mayores demuestran que los adultos producen mayor cantidad y diversidad de atributos que los niños, pero que ambas poblaciones comparten el núcleo del significado de los conceptos evaluados. Asimismo, muestra que la escolarización conduce a la generación de más atributos taxonómicos, que en los niños prevalecen los atributos introspectivos, que la densidad y la entropía revelan cómo los conceptos se vinculan entre sí diferencialmente en ambas poblaciones y finalmente que, frente a la dificultad para encontrar definidoras de pertenencia a una clase, los niños recurren a operaciones de contraste categorial. Entre las redes semánticas de adultos y de niños se encuentran continuidades y divergencias. En ambos grupos se encuentran separadas las emociones positivas de las negativas, lo cual es consistente con las teorías que sostienen la importancia de la valencia hedónica en la comprensión de las emociones.

Myotonic dystrophy 2 (DM2) is a genetic multi-systemic disease primarily affecting skeletal muscle. It is caused by CCTGn expansion in intron 1 of the CNBP gene, which encodes a zinc finger protein. DM2 disease has been successfully modeled in Drosophila melanogaster, allowing the identification and validation of new pathogenic mechanisms and potential therapeutic strategies. Here, we describe the principal tools used in Drosophila to study and dissect molecular pathways related to muscular dystrophies and summarize the main findings in DM2 pathogenesis based on DM2 Drosophila models. We also illustrate how Drosophila may be successfully used to generate a tractable animal model to identify novel genes able to affect and/or modify the pathogenic pathway and to discover new potential drugs.

Resumo Este estudo teve como objetivo compreender a produção de sentidos de trabalho e escola entre adolescentes que vivenciam a experiência de trabalhar e estudar. A pesquisa se fundamentou na Teoria da Subjetividade, principalmente no conceito de sentido subjetivo. Participaram deste estudo quatro adolescentes residentes em zonas urbanas e rurais do estado da Bahia, do sexo masculino e feminino. Foram realizadas sessões de conversação e utilizado um questionário sociodemográfico e uma complementação de frases. Os resultados apontaram a valorização do trabalho, visto como espaço formativo e promotor de valores, de garantia de acesso a bens de consumo e superação das privações impostas pela pobreza. A escola foi representada como ambiente de aprendizados e preparação para o futuro e mecanismo auxiliar para a consecução de aspirações profissionais. Estes resultados podem auxiliar na formulação e no aprimoramento de políticas públicas que visam à garantia de direitos e proteção ao adolescente trabalhador.

Objetivo. Estudiar la relación entre el tipo de mentalidad y el desempeño en comprensión lectora y aritmética de 247 estudiantes de 9 a 12 años de edad de dos escuelas de Argentina. Método. Los participantes completaron un cuestionario basado en una Escala de Mentalidad de Crecimiento y pruebas estandarizadas de comprensión lectora y cálculo aritmético. Además, se utilizaron las calificaciones escolares proporcionadas por docentes y datos sobre el estatus social (ES) aportados por padres/cuidadores. El diseño fue no experimental y transversal. Resultados. Los análisis de regresión jerárquica mostraron que a mayor mentalidad de crecimiento, mejor desempeño escolar, aún al controlar el efecto del ES. La relación del desempeño con las calificaciones fue más fuerte que con las pruebas estandarizadas.

BackgroundFall risk in the elderly is a major public health issue due to the injury-related consequences and the risk of associated long-term disability. However, delivering preventive interventions in usual clinical practice still represents a challenge.AimTo evaluate the efficacy of a multiple-component combined with a multifactorial personalized intervention in reducing fall rates in a mixed population of community-dwelling elderly compared to usual care.DesignRandomized Controlled Trial (NCT03592420, clinicalTrials.gov).SettingOutpatients in two Italian centers.Population403 community-dwelling elderly at moderate-to-high fall risk, including subjects with Parkinson's Disease and stroke.MethodsAfter the randomization, the described interventions were administered to the intervention group (n = 203). The control group (n = 200) received usual care and recommendations to minimize fall risk factors. In addition, each participant received a fall diary, followed by 12 monthly phone calls. The primary endpoint was the total number of falls in each group over 12 months, while the secondary endpoints were other fall-related indicators recorded at one year. In addition, participants' functioning was assessed at baseline (T1) and 3-month (T3).Results690 falls were reported at 12 months, 48.8% in the intervention and 51.2% in the control group, with 1.66 (± 3.5) and 1.77 (± 3.2) mean falls per subject, respectively. Subjects with ≥ 1 fall and ≥2 falls were, respectively, 236 (58.6%) and 148 (36.7%). No statistically significant differences were observed between groups regarding the number of falls, the falling probability, and the time to the first fall. According to the subgroup analysis, no significant differences were reported. However, a statistically significant difference was found for the Mini-BESTest (p = 0.004) and the Fullerton Advanced Balance Scale (p = 0.006) for the intervention group, with a small effect size (Cohen's d 0.26 and 0.32, respectively), at T1 and T3 evaluations.ConclusionsThe intervention was ineffective in reducing the number of falls, the falling probability, and the time to the first fall at 12 months in a mixed population of community-dwelling elderly. A significant improvement for two balance indicators was recorded in the intervention group. Future studies are needed to explore different effects of the proposed interventions to reduce falls and consequences.

Este trabalho apresenta o estudo realizado em uma Estação Elevatória de Esgoto após ser constatado severa degradação. O ataque por ácido sulfúrico biogênico em sistemas de esgoto sanitário é amplamente estudado na literatura, entretanto, dados em situações reais de obra ainda são bastante limitados. Foram realizadas análises da concentração de H_2 S no ar, profundidade de carbontação, ensaio de resistência à compressão, petrográfia, MEV/EDS, DRX e determinações químicas em testemunhos de concreto extraídos acima do nível do efluente. Os produtos identificados na superfície foram Gipsita, Jarosita, Hidróxido Ferroso, Cloreto Ferroso e possivelmente Hisingerita. Os resultados demonstram a presença na superfície tanto de produtos oriundos da dissolução da pasta cimenticia quanto das barras de aço de 16 mm localizadas na região atacada.

ABSTRACT Eukaryotic Translation Initiation Factor 5A (EIF5A) is a translation factor regulated by hypusination, a unique posttranslational modification catalyzed by deoxyhypusine synthetase (DHPS) and deoxyhypusine hydroxylase (DOHH) starting from the polyamine spermidine. Emerging data are showing that hypusinated EIF5A regulates key cellular processes such as autophagy, senescence, polyamine homeostasis, energy metabolism, and plays a role in cancer. However, the effects of EIF5A inhibition in preclinical cancer models, the mechanism of action, and specific translational targets are still poorly understood. We show here that hypusinated EIF5A promotes growth of colorectal cancer (CRC) cells by directly regulating MYC biosynthesis at specific pausing motifs. Inhibition of EIF5A hypusination with the DHPS inhibitor GC7 or through lentiviral-mediated knockdown of DHPS or EIF5A reduces the growth of various CRC cells. Multiplex gene expression analysis reveals that inhibition of hypusination impairs the expression of transcripts regulated by MYC, suggesting the involvement of this oncogene in the observed effect. Indeed, we demonstrate that EIF5A regulates MYC elongation without affecting its mRNA content or protein stability, by alleviating ribosome stalling at five distinct pausing motifs in MYC CDS. Of note, we show that blockade of the hypusination axis elicits a remarkable growth inhibitory effect in preclinical models of CRC and significantly reduces the size of polyps in APCMin/+ mice, a model of human familial adenomatous polyposis (FAP). Together, these data illustrate an unprecedented mechanism, whereby the tumor-promoting properties of hypusinated EIF5A are linked to its ability to regulate MYC elongation and provide a rationale for the use of DHPS/EIF5A inhibitors in CRC therapy.

Salvatore Sardo,1,2 Maura Galletta,2 Erica Coni,3 Cesar Ivan Aviles Gonzalez,1 Ilenia Piras,4 Giorgio Pia,4 Maurizio Evangelista,5 Mario Musu,1,2 Gabriele Finco1,2 1Anesthesia and Intensive Care Unit, University of Cagliari, Cagliari, Italy; 2Department of Medical Sciences and Public Health, University of Cagliari, Cagliari, Italy; 3RN-BC, University of Cagliari, Cagliari, Italy; 4ATS Sardegna, ASSL Cagliari SS, Cagliari, Italy; 5Department of Anesthesiology and Pain Medicine, Cattolica University, Rome, ItalyCorrespondence: Maura GallettaDepartment of Medical Sciences and Public Health, University of Cagliari, Highway 554 (exit for Sestu), Monserrato 09042, Cagliari, ItalyTel +39 070-675-3108Email maura.galletta@gmail.comPurpose: The aim of this prospective study was to assess the behavior of emergency department (ED) nurses with regard to pain and their role in pain management in a real-life clinical setting.Methods: A total of 509 consecutive patients were enrolled during a 6-week period. A case-report form was used to collect data on nurses’ approaches to pain, time to analgesia provision, and patient-perceived quality of analgesia.Results: Triage nurses actively inquired about pain in almost every case, but they did not estimate pain intensity in a third of patients. In the majority of cases, triage nurses did not report pain-related findings to the physician, who was the only professional that could prescribe analgesia to patients. The assignment of the color-coding of triage by nurses appears to be related to the perceived severity of the clinical case and a more comprehensive evaluation of pain. More than half of patients were at least fairly satisfied with analgesia.Conclusion: Pain is increasingly screened during triage, but its comprehensive assessment and management still lack systematic application. We believe that further education and implementation of analgesia protocols may empower nurses to manage ED patients’ pain more effectively and in a more timely manner.Keywords: emergency, ED, nurse, oligoanalgesia, pain, triage

Sugar reduction is one of the essential macronutrients used as energy sources. High levels of sugar reduction in food can increase the sweet taste of these foodstuffs. However, the consumption of high sugar food can cause diabetes mellitus. The purpose of this study is to increase the economic value of liquid palm sugar (Borassus flabellifer L) and opportunities as a preservative in the food industry. This research used quantitative descriptive methods. The results showed that the level of sugar reduction in siwalan liquid brown sugar (Borassus flabellifer L) was 15.65%, the water content in the liquid palm sugar sample (Borassus flabellifer L) is 26.78%, and the temperature of the liquid brown sugar after cooking is 230C. The effect of heat or temperature on cooking also causes physical changes in liquid brown sugar such as caramel formation, color and flavour.

Indonesia has marine biological natural resources consisting of fish, seaweed, crabs and shrimp which are very potential. The purpose of this study was to determine the composition of pigments in Ulva sp (Chlorophyta), Padina australis (Paeophyta) and Hypnea sp (Rhodophyta) obtained from Tablolong waters. The method used in this research is descriptive qualitative and quantitative. Proof of pigment in samples using thin layer chromatography (TLC). The results of pigment analysis of Ulva sp obtained twelve color spots with identified pigment types consisting of chlorophyll a, chlorophyll b, xanthophyll, b-carotene and feofitin. The pigment content identified in Padina australis samples are chlorophyll b, feoforbid, xanthophyll, chlorophyll a, carotene and feofitin a. The types of pigments identified in Ulva sp include pigment chlorophyll a, chlorophyll b, carotene and feofitin from the total color spots formed. Based on the results of this study concluded that non-cultivated seaweed obtained from Tablolong waters contains carotenoid and chlorophyll pigments. Suggestions from this study are expected to do an analysis of pigment content analysis in the dry season time period and continued with antioxidant testing. Indonesia memiliki Sumber Daya Alam hayati laut yang terdiri dari ikan, rumput laut, kepiting dan udang yang sangat potensial. Tujuan penelitian ini adalah untuk mengetahui komposisi pigmen pada Ulva sp (Chlorophyta), Padina australis (Paeophyta) dan Hypnea sp (Rhodophyta) yang diperoleh dari perairan Tablolong. Metode yang digunakan dalam penelitian ini adalah deskriptif kualitatif dan kuantitatif. Pembuktian pigmen pada sampel menggunakan Kromatografi lapis tipis (KLT). Hasil analisis pigmen dari Ulva sp diperoleh dua belas spot warna dengan jenis pigmen yang teridentifikasi terdiri dari klorofil a, klorofil b, xantofil, b-karoten dan feofitin. Kandungan pigmen yang teridentifikasi pada sampel Padina australis adalah klorofil b, feoforbid, xantofil, klorofil a, karoten dan feofitin a. Jenis pigmen yang teridentifikasi pada Ulva sp meliputi pigmen klorofil a, klorofil b, karoten dan feofitin dari total spot warna yang terbentuk. Berdasarkan hasil penelitian dapat disimpulkan bahwa rumput laut non budidaya yang diperoleh dari perairan Tablolong memiliki kandungan pigmen karotenoid dan klorofil. Saran dari penelitian ini diharapkan dilakukan peneltian analisis kandungan pigmen pada periode waktu musim kemarau serta dilanjutkan dengan uji antioksidan.

El estudio de la organización del conocimiento en la memoria semántica suscita gran interés en Psicología Cognitiva y Neuropsicología. El conocimiento semántico está representado por conceptos que comparten características y forman una jerarquía inclusiva -organización taxonómica-, o que se vinculan en tiempo y espacio -organización temática o situacional-. Se considera que a lo largo del desarrollo cambia la preferencia por estos tipos de organización, pero son pocos los estudios que comparan las organizaciones conceptuales de niños en edad escolar, adultos jóvenes y mayores, y sus resultados son divergentes. Asimismo, la organización conceptual también varía en función del dominio al que pertenece el concepto (vivo vs no vivo). Por lo tanto, el objetivo general de este estudio fue estudiar qué tipos de organización conceptual empleaban esos grupos en una tarea de producción de atributos para conceptos de seres vivos y no vivos. Los resultados indican que la producción de atributos taxonómicos fue significativamente mayor para los adultos jóvenes que para los adultos mayores y los niños, en tanto la producción taxonómica de estos dos últimos grupos fue pareja. En cuanto a la producción temática, fue alta y homogénea en los tres grupos de edad. Por último, para el dominio de los seres no vivos los atributos resultaron en su mayoría temáticos y perceptivos, y para el dominio de los seres vivos, mayormente perceptivos.

El presente estudio tuvo como objetivo desarrollar y validar el Cuestionario de Funciones Ejecutivas (CuFE), un cuestionario accesible para evaluar las tres principales funciones ejecutivas (memoria de trabajo, inhibición y flexibilidad cognitiva) en niños de 9 a 12 años y, así, proporcionar valores descriptivos de referencia y evidencias acerca de su confiabilidad y validez. Para ello se analizó su funcionamiento en una muestra de 269 niños argentinos de 9 a 12 años de edad, alumnos del segundo ciclo de la escuela primaria. El análisis factorial exploratorio reveló una estructura de tres factores que explicaban 49.08 % de la varianza, con cargas factoriales unidimensionales y satisfactorias. Los factores retenidos presentaron buenos índices de confiabilidad y fueron llamados: memoria de trabajo, inhibición y flexibilidad y control emocional. La memoria de trabajo se asoció con la comprensión lectora, el cálculo matemático y las calificaciones escolares de Prácticas del lenguaje y Matemática. Las restantes dos subescalas se asociaron con las calificaciones escolares de ambas asignaturas. Las dimensiones del cuestionario coinciden con los actuales modelos teóricos de funcionamiento ejecutivo. En función de las evidencias de validez y confiabilidad, el CuFE se presenta como un instrumento ecológico y valioso para la medición de las funciones ejecutivas en el contexto de la evaluación infantil.

BackgroundKRAS mutations in metastatic colorectal cancer (mCRC) define a subset of tumors that have primary resistance to anti-EGFR-based therapy. Data concerning whether different KRAS mutations may also have a prognostic value are lacking. Furthermore, novel KRAS G12C inhibitors are currently in development. The aim of our analysis was to compare response rates in patients treated with first-line chemotherapy doublet + Bevacizumab among different KRAS variants. Secondary end-points were progression free survival (PFS) and overall survival (OS).MethodsPatients with KRAS mutated mCRC treated with either FOLFIRI/FOLFOX/XELOX + Bevacizumab were eligible for enrollment. Patients whose tumor harbored NRAS mutations or that coexpressed also BRAF mutations were excluded from this retrospective analysis. Patients’ individual data were collected from patients’ records. Propensity score matching (nearest method, 1:2 ratio) was used to define the two different groups of patients for comparison (KRAS G12C mutated vs other KRAS variants). Eastern Cooperative Oncology Group Performance Status (ECOG PS), sex, metastatic site of involvement, synchronous vs metachronous metastatic disease, tumor sidedness, mucinous histology, primary tumor surgery, more than two lines of treatment for metastatic disease, and radical surgery of metastases were used as matching factors. Response rate (RR) was calculated by RECIST 1.1 criteria. Both progression free-survival and overall survival were calculated by Kaplan–Meier method. Categorical variables were compared by Fisher exact test for binomial variables and by chi-square test for all other instances. The level of statistical significance p was set at 0.05 for all tests.ResultsA total of 120 patients were assessed in the final analysis. Out of the 120 patients, 15 (12%) were KRAS G12C mutated. In the whole cohort of patients, 59/120 (49%) had partial response (PR), 42/120 (35%) had stable disease (SD), and 19/120 (16%) had progressive disease (PD) as the best response. In KRAS G12C patients, 4/15 (27%) had PR, 6/15 (40%) had SD, and the remaining 5/15 (33%) had PD as the best response. In patients with other KRAS mutations, 55/105 (52%) had PR, 37/105 (35%) had SD, and the remaining 13/105 (12%) had PD as the best response. The difference in RR between the two groups of patients was statistically significant (p=0.017). On the other hand, no difference in PFS (p=0.76) and OS (p=0.56) was observed. After matching procedures, the difference in response rates between KRAS G12C mutated patients vs the matched cohort of patients with other KRAS mutations remained statistically significant (p=0.016). KRAS G12C mutations were not associated with differences in sites of metastatic involvement, sex, and ECOG PS. On the other hand, synchronous vs metachronous metastatic disease (p=0.039), age > 75 years (p=0.043), and mucinous histology (p=0.008) were more frequent in G12C mutated tumors.ConclusionsIn our cohort of patients, it was observed that KRAS G12C mutations are associated with worse response rates compared to other KRAS variants when treated with standard chemotherapy doublet + Bevacizumab. On the other hand, both PFS and OS were not significantly different. Based on these findings, we believe that new treatment options focused on KRAS G12C inhibition should be tested mainly in first-line setting and in addition to standard chemotherapy doublet + Bevacizumab for mCRC patients, as they might “fill the gap” in response rates that was seen in our study.

Microsatellite expansions of CCTG repeats in the cellular nucleic acid-binding protein (CNBP) gene leads to accumulation of toxic RNA and have been associated with myotonic dystrophy type 2 (DM2). However, it is still unclear whether the dystrophic phenotype is also linked to CNBP decrease, a conserved CCHC-type zinc finger RNA-binding protein that regulates translation and is required for mammalian development. Here, we show that depletion of Drosophila CNBP in muscles causes ageing-dependent locomotor defects that are correlated with impaired polyamine metabolism. We demonstrate that the levels of ornithine decarboxylase (ODC) and polyamines are significantly reduced upon dCNBP depletion. Of note, we show a reduction of the CNBP-polyamine axis in muscles from DM2 patients. Mechanistically, we provide evidence that dCNBP controls polyamine metabolism through binding dOdc mRNA and regulating its translation. Remarkably, the locomotor defect of dCNBP-deficient flies is rescued by either polyamine supplementation or dOdc1 overexpression. We suggest that this dCNBP function is evolutionarily conserved in vertebrates with relevant implications for CNBP-related pathophysiological conditions.

The paper reports the results obtained during an experimental research conducted in real working conditions of road embankment made with C&DW. For this purpose an experimental road, 30 m long, 4 m wide and 4 m high was built, installing 12 instruments: 3 pressure cells to measure stresses and 9 Linear Variable Differential Transformers (LVDTs) to measure deformations. The data were collected under different load and traffic speed magnitude. At this point of the research data are being analysed and compared, and the results reported on this paper.

Biguanides are a family of antidiabetic drugs with documented anticancer properties in preclinical and clinical settings. Despite intensive investigation, how they exert their therapeutic effects is still debated. Many studies support the hypothesis that biguanides inhibit mitochondrial complex I, inducing energy stress and activating compensatory responses mediated by energy sensors. However, a major concern related to this “complex” model is that the therapeutic concentrations of biguanides found in the blood and tissues are much lower than the doses required to inhibit complex I, suggesting the involvement of additional mechanisms. This comprehensive review illustrates the current knowledge of pharmacokinetics, receptors, sensors, intracellular alterations, and the mechanism of action of biguanides in diabetes and cancer. The conditions of usage and variables affecting the response to these drugs, the effect on the immune system and microbiota, as well as the results from the most relevant clinical trials in cancer are also discussed.

Overfishing is notorious for triggering population collapses and disrupting marine biological functioning worldwide. To counter such a threat, policy-makers have created and implemented multiple management strategies, but most were incapable to prevent the decline of several key species. Here, we discuss a new management strategy in force since June 2019 in Brazil that aims to deter the overfishing of parrotfish species of the genera Scarus and Sparisoma. This innovative strategy, here referred to as inverted management, allows the capture of endangered parrotfish species inside management areas, such as partially protected marine areas—MPAs, but bans it elsewhere. This initiative is supposed to be built in a partnership among the government, scientists, managers, and fishers. If implemented correctly, endangered species would recover in the much larger area outside MPAs, and fishers would benefit from the conservation-value of the scarce and valued product. However, to succeed, the strategy depends on the adoption of a series of challenging management rules that are not currently being enforced along an extensive coastline. So far, few MPAs have incorporated rules for endangered species in their management plan, and those that have done so have no plans or the means to enforce them. Therefore, fishing of endangered species is currently ongoing without any management or monitoring in the entire Brazilian coast. Concerned with the challenges to develop plans to recover populations of endangered species faced by Brazilian managers, we suggest wide communication and a ban on the fisheries until management plans are implemented. Additionally, we suggest that the effectiveness of the inverted management strategy for parrotfishes should be assessed before it’s applied to other endangered species.

OBJECTIVE: ISL1 is a pioneer transcription factor that plays important roles in cell lineage specification and differentiation, by programming the epigenome and recruiting additional regulatory factors. The aim of this study is to determine whether the human breastmilk contains ISL1-positive stem cells, and, if so, to describe the subcellular localization of ISL1. MATERIALS AND METHODS: Breast milk was obtained from fourteen healthy females during the first 2-6 months of lactation. Cell morphology was examined in the breast milk with the automatic ThinPrep® processor (Hologic® Inc.) in commercial Cytological ThinPrep® solution (Hologic ® Inc.), followed by standard immunohistochemical staining of ISL1. RESULTS: ISL1 had a granular diffuse cytoplasmic localization, with varying intensity of staining in both single and grouped cells. Nuclear staining was also present, as was staining of intracellular and extracellular vesicles with ISL1 antibody. CONCLUSIONS: These preliminary results suggest that ISL1 could distinguish a readily available source of putative stem cells in human breast milk. These stem cells may complete the network created between the mother and the newborn during gestation, thereby improving the efficiency of programming and reprogramming postnatal events. [ABSTRACT FROM AUTHOR]

Il progetto di ricerca sulla musica nel circo contemporaneo, con un focus sul Circo Paniko, nasce nel 2018 quando il collettivo nomade approda a Cagliari. Tale ricerca ha seguito la metodologia della ricerca sul campo di stampo etnomusicologico, utilizzando la registrazione audiovisiva e successivamente la stesura di un articolo col fine di comprendere il modo attraverso il quale la compagnia sviluppa le proprie creazioni artistiche - con particolare interesse alla sfera musicale - di indagare sull’esistenza di uno o più stili musicali loro caratteristici e per analizzare la performance nel suo intero come evento collettivo e condiviso. Quest’ultima è stata scomposta tramite l’analisi frame by frame di un numero di danza aerea sui tessuti presente sia all’interno del Cabaret rappresentato a Cagliari (2018/2019), sia in Panikyuuri, messo in scena ad Assemini (2019/2020).

Balloon cell nevus (BCN) is a rare variant of benign melanocytic nevus. Clinically, BCN appears similar to regular compound melanocytic nevi. Histopathologically, the balloon cells appear as large, round, polygonal cells with small, round, centrally placed basophilic nuclei, and clear, pale or foamy cytoplasm. We report a case of BCN occurring on the vulva of an adolescent and review the literature on this rare variant of melanocytic nevus, including the differential diagnoses of balloon cells. Recognition of a BCN and differentiating it from other pale cell tumors and balloon cell melanoma is important as it impacts on subsequent management options and prognosis.

Thymosin β4 (Tβ4) was extracted forty years agofrom calf thymus. Since then, it has been identified as a G-actin binding protein involved in blood clotting, tissue regeneration, angiogenesis, and anti-inflammatory processes. Tβ4 has also been implicated in tumor metastasis and neurodegeneration. However, the precise roles and mechanism(s) of action of Tβ4 in these processes remain largely unknown, with the binding of the G-actin protein being insufficient to explain these multi-actions. Here we identify for the first time the important role of Tβ4 mechanism in ferroptosis, an iron-dependent form of cell death, which leads to neurodegeneration and somehow protects cancer cells against cell death. Specifically, we demonstrate four iron2+ and iron3+ binding regions along the peptide and show that the presence of Tβ4 in cell growing medium inhibits erastin and glutamate-induced ferroptosis in the macrophage cell line. Moreover, Tβ4 increases the expression of oxidative stress-related genes, namely BAX, hem oxygenase-1, heat shock protein 70 and thioredoxin reductase 1, which are downregulated during ferroptosis. We state the hypothesis that Tβ4 is an endogenous iron chelator and take part in iron homeostasis in the ferroptosis process. We discuss the literature data of parallel involvement of Tβ4 and ferroptosis in different human pathologies, mainly cancer and neurodegeneration. Our findings confronted with literature data show that controlled Tβ4 release could command on/off switching of ferroptosis and may provide novel therapeutic opportunities in cancer and tissue degeneration pathologies.

El objetivo de este trabajo fue analizar la relación de las estrategias de regulación emocional reevaluación cognitiva aplicada a tareas escolares para el hogar (RC-TEH) y manejo emocional aplicado a tareas escolares para el hogar (ME-TEH) sobre el desempeño académico (DA) controlando dificultades de memoria de trabajo (dif-MT) en niños que finalizaban la Educación Primaria. Se administró un cuestionario de autoinforme para evaluar la RC-TEH y el ME-TEH a 119 de niños de cuarto, quinto y sexto grado (9 a 11 años de edad) y dos cuestionarios a sus maestros para evaluar su DA y dificultades de MT. Los resultados mostraron que el ME-TEH se asoció con las dimensiones éxito, productividad académica, matemáticas y lectura del DA, incluso cuando se controlaron dif-MT. No se observaron asociaciones significativas de la RC-TEH con el DA, ni de ninguna de las estrategias sobre el control del impulso en situaciones académicas. Se espera que los resultados profundicen en el conocimiento del rol de la regulación emocional en el DA y contribuyan así al contenido de programas de promoción de la regulación emocional diseñados para contextos escolares.

Extensive molecular characterization of human colorectal cancer (CRC) via Next Generation Sequencing (NGS) indicated that genetic or epigenetic dysregulation of a relevant, but limited, number of molecular pathways typically occurs in this tumor. The molecular picture of the disease is significantly complicated by the frequent occurrence of individually rare genetic aberrations, which expand tumor heterogeneity. Inter- and intratumor molecular heterogeneity is very likely responsible for the remarkable individual variability in the response to conventional and target-driven first-line therapies, in metastatic CRC (mCRC) patients, whose median overall survival remains unsatisfactory. Implementation of an extensive molecular characterization of mCRC in the clinical routine does not yet appear feasible on a large scale, while multigene panel sequencing of most commonly mutated oncogene/oncosuppressor hotspots is more easily achievable. Here, we report that clinical multigene panel sequencing performed for anti-EGFR therapy predictive purposes in 639 formalin-fixed paraffin-embedded (FFPE) mCRC specimens revealed previously unknown pairwise mutation associations and a high proportion of cases carrying actionable gene mutations. Most importantly, a simple principal component analysis directed the delineation of a new molecular stratification of mCRC patients in eight groups characterized by non-random, specific mutational association patterns (MAPs), aggregating samples with similar biology. These data were validated on a The Cancer Genome Atlas (TCGA) CRC dataset. The proposed stratification may provide great opportunities to direct more informed therapeutic decisions in the majority of mCRC cases.

En este trabajo evaluamos comparativamente raspadores del Holoceno medio y tardío del centro-oeste de Santa Cruz (Patagonia) a los fines de discutir acerca de la variabilidad de los conjuntos en el contexto de cambios ambientales que se dieron durante el Holoceno. Dicha comparación abarca escalas espaciales y temporales amplias y se realiza sobre la base de variables morfológicas y métricas. Los resultados indican que no existen diferencias significativas entre los raspadores de uno y otro período a excepción del espesor de aquellos confeccionados en sílice. Se discuten las implicancias en términos de las estrategias implementadas por los cazadores-recolectores en contextos ambientales específicos.