Cannabigerol Is a Potential Therapeutic Agent in a Novel Combined Therapy for Glioblastoma

Glioblastoma is the most aggressive cancer among primary brain tumours. As with other cancers, the incidence of glioblastoma is increasing; despite modern therapies, the overall mean survival of patients post-diagnosis averages around 16 months, a figure that has not changed in many years. Cannabigerol (CBG) has only recently been reported to prevent the progression of certain carcinomas and has not yet been studied in glioblastoma. Here, we have compared the cytotoxic, apoptotic, and anti-invasive effects of the purified natural cannabinoid CBG together with CBD and THC on established differentiated glioblastoma tumour cells and glioblastoma stem cells. CBG and THC reduced the viability of both types of cells to a similar extent, whereas combining CBD with CBG was more efficient than with THC. CBD and CBG, both alone and in combination, induced caspase-dependent cell apoptosis, and there was no additive THC effect. Of note, CBG inhibited glioblastoma invasion in a similar manner to CBD and the chemotherapeutic temozolomide. We have demonstrated that THC has little added value in combined-cannabinoid glioblastoma treatment, suggesting that this psychotropic cannabinoid should be replaced with CBG in future clinical studies of glioblastoma therapy

Thirty-Second Sit-To-Stand Test as an Alternative for Estimating Peak Oxygen Uptake and 6-Min Walking Distance in Women With Breast Cancer: A Cross-Sectional Study

[Abstract] Purpose: To determine whether the 30-s sit-to-stand (30STS) test can be a valid tool for estimating and stratifying peak oxygen uptake (VO2peak) and 6-min walking distance (6MWD) in women with breast cancer. Methods: This cross-sectional study uses data from the ONCORE randomized controlled trial, including 120 women aged 18-70 years with early-stage breast cancer under treatment with anthracycline and/or anti-HER2 antibodies. Participant characteristics were collected at baseline and pooled data from functional assessment (30STS test, relative and absolute VO2peak, and 6MWD) were collected at baseline and post-intervention (comprehensive cardio-oncology rehabilitation program vs. usual care). Bivariate correlations and multivariate linear regression analyses were performed to study the relationship between functional test variables. Results: The number of repetitions in the 30STS test showed (i) a moderate correlation with relative VO2peak (ml/kg/min) (r = 0.419; p < 0.001; n = 126), (ii) a weak correlation with absolute VO2peak (ml/min) (r = 0.241; p = 0.008; n = 120), and (iii) a moderate correlation with the 6MWD (r = 0.440; p < 0.001; n = 85). The ONCORE equations obtained from the multivariate regression models allowed the estimation of VO2peak and 6MWD (r2 = 0.390; r2 = 0.261, respectively) based on the 30STS test, and its stratification into tertiles (low, moderate, and high). Conclusion: The 30STS test was found to be a useful tool to estimate VO2peak and/or 6MWD in women with early-stage breast cancer. Its use may facilitate the assessment and stratification of functional capacity in this population for the implementation of therapeutic exercise programs if cardiopulmonary exercise testing (CPET) or 6MWT are not available.Open Access funding provided thanks to the CRUE-CSIC agreement with Springer Nature. This work was supported by a competitive grant from the Asociación Española Contra el Cáncer (AECC) Scientific Foundation — PRDLC21480DÍAZ — and by a competitive grant of the Spanish Health Research Fund of the Carlos III Health Institute (ISCIII) — PI17/01687, co-funded FEDER, through Strategic Action in Healthcare, 2017. The ISCIII is the national and international reference in biomedical research and public health in Spain. The AECC Scientific Foundation and the ISCIII had no role in study design, data collection, data analysis, data interpretation, or writing of the report. Funding for open access charge will be supported by Universidade da Coruña/CISUGFundación Científica Asociación Española Contra el Cáncer; PRDLC21480DÍA

Brief Report: Hispanic Patients\u27 Trajectory of Cancer Symptom Burden, Depression, Anxiety, and Quality of Life

Background: Anxiety and depression symptoms are known to increase cancer symptom burden, yet little is known about the longitudinal integrations of these among Hispanic/Latinx patients. The goal of this study was to explore the trajectory and longitudinal interactions among anxiety and depression, cancer symptom burden, and health-related quality of life in Hispanic/Latinx cancer patients undergoing chemotherapy. METHODS: Baseline behavioral assessments were performed before starting chemotherapy. Follow-up behavioral assessments were performed at 3, 6, and 9 months after starting chemotherapy. Descriptive statistics, chi-square tests, Fisher\u27s exact tests, and Mann-Whitney tests explored associations among outcome variables. Adjusted multilevel mixed-effects linear regression models were also used to evaluate the association between HADS scores, follow-up visits, FACT-G scale, MDASI scale, and sociodemographic variables. RESULTS: Increased cancer symptom burden was significantly related to changes in anxiety symptoms\u27 scores (adjusted beta^ = 0.11 [95% CI: 0.02, 0.19]. Increased quality of life was significantly associated with decreased depression and anxiety symptoms (adjusted beta^ = -0.33; 95% CI: -0.47, -0.18, and 0.38 adjusted beta^= -0.38; 95% CI: -0.55, -0.20, respectively). CONCLUSIONS: Findings highlight the need to conduct periodic mental health screenings among cancer patients initiating cancer treatment

Perception of the Integral Development of University Students: A Psycho-Pedagogical View

La investigación psicopedagógica en la Universidad Veracruzana se centra en comprender el desarrollo educativo de los estudiantes a nivel licenciatura, el presente estudio analiza las siguientes dimensiones: aspectos académicos, emocionales, sociales y espirituales, a fin de plantear estrategias educativas significativas que promuevan el desarrollo integral. Se elaboró un instrumento para la evaluación de hábitos de estudio, relaciones interpersonales, dinámica familiar, resolución de conflictos y salud mental, entre otros que cuenta con 71 ítems en una escala tipo Likert, cuenta con un Alfa de 0.892. La metodología empleada fue mixta con un alcance descriptivo, la muestra fue de 2,302 estudiantes de nivel licenciatura de la Universidad Veracruzana, México, de la región Veracruz. El estudio busca identificar necesidades psicopedagógicas latentes que obstaculizan el éxito académico, con el objetivo de implementar estrategias de intervención y reducir el rezago educativo. Esta investigación integral no solo beneficia al ámbito educativo, sino también al desarrollo personal y profesional de los estudiantes y, en última instancia, a la sociedad en general.Psychopedagogical research at the Universidad Veracruzana focuses on understanding the educational development of undergraduate students. This study analyzes the following dimensions: academic, emotional, social and spiritual aspects, in order to propose meaningful educational strategies that promote integral development. An instrument was developed for the evaluation of study habits, interpersonal relationships, family dynamics, conflict resolution and mental health, among others, with 71 items on a Likert-type scale, with an Alpha of 0.892. The methodology used was mixed with a descriptive scope; the sample consisted of 2,302 undergraduate students of the Universidad Veracruzana, Mexico, from the Veracruz region. The study seeks to identify latent psycho-pedagogical needs that hinder academic success, with the objective of implementing intervention strategies and reducing educational lag. This comprehensive research not only benefits the educational field, but also the personal and professional development of students and, ultimately, society in general

Aligned ovine diaphragmatic myoblasts overexpressing human connexin-43 seeded on poly (L-lactic acid) scaffolds for potential use in cardiac regeneration

Diaphragmatic myoblasts (DMs) are precursors of type-1 muscle cells displaying high exhaustion threshold on account that they contract and relax 20 times/min over a lifespan, making them potentially useful in cardiac regeneration strategies. Besides, it has been shown that biomaterials for stem cell delivery improve cell retention and viability in the target organ. In the present study, we aimed at developing a novel approach based on the use of poly (L-lactic acid) (PLLA) scaffolds seeded with DMs overexpressing connexin-43 (cx43), a gap junction protein that promotes inter-cell connectivity. DMs isolated from ovine diaphragm biopsies were characterized by immunohistochemistry and ability to differentiate into myotubes (MTs) and transduced with a lentiviral vector encoding cx43. After confirming cx43 expression (RT-qPCR and Western blot) and its effect on inter-cell connectivity (fluorescence recovery after photobleaching), DMs were grown on fiberaligned or random PLLA scaffolds. DMs were successfully isolated and characterized. Cx43 mRNA and protein were overexpressed and favored inter-cell connectivity. Alignment of the scaffold fibers not only aligned but also elongated the cells, increasing the contact surface between them. This novel approach is feasible and combines the advantages of bioresorbable scaffolds as delivery method and a cell type that on account of its features may be suitable for cardiac regeneration. Future studies on animal models of myocardial infarction are needed to establish its usefulness on scar reduction and cardiac function.Centro de Investigaciones Cardiovasculare

Bienestar Animal Ovino. Estándares de bienestar animal para la cría, la faena y el transporte de ovinos. Guía de aplicación

La definición de los Estándares de Bienestar Animal es parte de un proceso de innovación en la cadena de producción ovina. Constituyen una parte central del programa de aseguramiento de la calidad impulsado por el gobierno junto a los productores, transportistas y la industria. Para redactar este documento se realizó una consulta a especialistas de los diferentes eslabones de la cadena, a científicos y a referentes de organizaciones de defensa de derechos de los animales. En consecuencia, los estándares propuestos se basan en el estado actual del conocimiento científico, las prácticas de manejo productivo e industrial recomendadas y las expectativas de la sociedad. Antes de su publicación se realizó una extensa consulta pública en la que se recogieron las sugerencias de productores, industriales y organizaciones de protección animal. La incorporación de estas sugerencias ayudó a mejorar el manuscrito, elevar el nivel de los estándares propuestos y enriquecer las recomendaciones.EEA Valle InferiorFil: Alvarez, Juan Mauricio. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Valle Inferior; ArgentinaFil: Vargas, Paola. Instituto Nacional de Tecnología Agropecuaria (INTA) Estación Experimental Agropecuaria Santa Cruz; ArgentinaFil: Racciatti, Débora. Servicio Nacional de Sanidad y Calidad Agroalimentaria (SENASA); ArgentinaFil: Pena, Sergio. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Santa Cruz; Argentina. Consejo Profesional de Ingeniería Agronómica; ArgentinaFil: Bain, Ingrid. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Chubut; ArgentinaFil: Lynch, Gloria. Universidad Nacional de Lomas de Zamora; ArgentinaFil: Odeón, Mercedes. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Bariloche; ArgentinaFil: González Ruíz, Eduardo. Cámara de Frigoríficos de la Patagonia; ArgentinaFil: Roselli, Paula. Ministerio de Agricultura, Ganadería y Pesca. Dirección de Ovinos, Caprinos y Camélidos; ArgentinaFil: Marino, Virginia Analía. Ministerio de Agricultura, Ganadería y Pesca. Dirección de Ovinos, Caprinos y Camélidos; ArgentinaFil: Ceballos, Demian. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Esquel; ArgentinaFil: Apostolo, Romina María. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Esquel; ArgentinaFil: Allona, Milagros. Federación Lanera Argentina; Argentin

Antiinflammatory Therapy with Canakinumab for Atherosclerotic Disease

Background: Experimental and clinical data suggest that reducing inflammation without affecting lipid levels may reduce the risk of cardiovascular disease. Yet, the inflammatory hypothesis of atherothrombosis has remained unproved. Methods: We conducted a randomized, double-blind trial of canakinumab, a therapeutic monoclonal antibody targeting interleukin-1β, involving 10,061 patients with previous myocardial infarction and a high-sensitivity C-reactive protein level of 2 mg or more per liter. The trial compared three doses of canakinumab (50 mg, 150 mg, and 300 mg, administered subcutaneously every 3 months) with placebo. The primary efficacy end point was nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death. RESULTS: At 48 months, the median reduction from baseline in the high-sensitivity C-reactive protein level was 26 percentage points greater in the group that received the 50-mg dose of canakinumab, 37 percentage points greater in the 150-mg group, and 41 percentage points greater in the 300-mg group than in the placebo group. Canakinumab did not reduce lipid levels from baseline. At a median follow-up of 3.7 years, the incidence rate for the primary end point was 4.50 events per 100 person-years in the placebo group, 4.11 events per 100 person-years in the 50-mg group, 3.86 events per 100 person-years in the 150-mg group, and 3.90 events per 100 person-years in the 300-mg group. The hazard ratios as compared with placebo were as follows: in the 50-mg group, 0.93 (95% confidence interval [CI], 0.80 to 1.07; P = 0.30); in the 150-mg group, 0.85 (95% CI, 0.74 to 0.98; P = 0.021); and in the 300-mg group, 0.86 (95% CI, 0.75 to 0.99; P = 0.031). The 150-mg dose, but not the other doses, met the prespecified multiplicity-adjusted threshold for statistical significance for the primary end point and the secondary end point that additionally included hospitalization for unstable angina that led to urgent revascularization (hazard ratio vs. placebo, 0.83; 95% CI, 0.73 to 0.95; P = 0.005). Canakinumab was associated with a higher incidence of fatal infection than was placebo. There was no significant difference in all-cause mortality (hazard ratio for all canakinumab doses vs. placebo, 0.94; 95% CI, 0.83 to 1.06; P = 0.31). Conclusions: Antiinflammatory therapy targeting the interleukin-1β innate immunity pathway with canakinumab at a dose of 150 mg every 3 months led to a significantly lower rate of recurrent cardiovascular events than placebo, independent of lipid-level lowering. (Funded by Novartis; CANTOS ClinicalTrials.gov number, NCT01327846.

Circulating microRNAs in sera correlate with soluble biomarkers of immune activation but do not predict mortality in ART treated individuals with HIV-1 infection: A case control study

Introduction: The use of anti-retroviral therapy (ART) has dramatically reduced HIV-1 associated morbidity and mortality. However, HIV-1 infected individuals have increased rates of morbidity and mortality compared to the non-HIV-1 infected population and this appears to be related to end-organ diseases collectively referred to as Serious Non-AIDS Events (SNAEs). Circulating miRNAs are reported as promising biomarkers for a number of human disease conditions including those that constitute SNAEs. Our study sought to investigate the potential of selected miRNAs in predicting mortality in HIV-1 infected ART treated individuals. Materials and Methods: A set of miRNAs was chosen based on published associations with human disease conditions that constitute SNAEs. This case: control study compared 126 cases (individuals who died whilst on therapy), and 247 matched controls (individuals who remained alive). Cases and controls were ART treated participants of two pivotal HIV-1 trials. The relative abundance of each miRNA in serum was measured, by RTqPCR. Associations with mortality (all-cause, cardiovascular and malignancy) were assessed by logistic regression analysis. Correlations between miRNAs and CD4+ T cell count, hs-CRP, IL-6 and D-dimer were also assessed. Results: None of the selected miRNAs was associated with all-cause, cardiovascular or malignancy mortality. The levels of three miRNAs (miRs -21, -122 and -200a) correlated with IL-6 while miR-21 also correlated with D-dimer. Additionally, the abundance of miRs -31, -150 and -223, correlated with baseline CD4+ T cell count while the same three miRNAs plus miR- 145 correlated with nadir CD4+ T cell count. Discussion: No associations with mortality were found with any circulating miRNA studied. These results cast doubt onto the effectiveness of circulating miRNA as early predictors of mortality or the major underlying diseases that contribute to mortality in participants treated for HIV-1 infection

Digital tools to improve parenting behaviour in low-income settings: a mixed-methods feasibility study

Introduction Digital parenting interventions could be potentially cost-effective means for providing early child development services in low-income settings. This 5-month mixed-methods pilot study evaluated the feasibility of using Afinidata, a comprehensive Facebook Messenger-based digital parenting intervention in a remote rural setting in Latin America and explored necessary adaptations to local context. Methods The study was conducted in three provinces in the Cajamarca region, Peru, from February to July 2021. 180 mothers with children aged between 2 and 24 months and regular access to a smartphone were enrolled. Mothers were interviewed three times in-person. Selected mothers also participated in focus groups or in-depth qualitative interviews. Results Despite the rural and remote study site, 88% of local families with children between 0 and 24 months had access to internet and smartphones. Two months after baseline, 84% of mothers reported using the platform at least once, and of those, 87% rated it as useful to very useful. After 5 months, 42% of mothers were still active on the platform, with little variation between urban and rural settings. Modifications to the intervention focused on assisting mothers in navigating the platform independently and included adding a laminated booklet with general information on child development, sample activities and detailed instructions on how to self-enrol in case of lost phones. Conclusions We found high access to smartphones and the intervention was well received and used in very remote areas of Peru, suggesting that digital parenting interventions could be a promising path forward for supporting low-income families in remote parts of Latin America.ISSN:0003-9888ISSN:1468-204

Aligned ovine diaphragmatic myoblasts overexpressing human connexin-43 seeded on poly (l-lactic acid) scaffolds for potential use in cardiac regeneration

Diaphragmatic myoblasts (DMs) are precursors of type-1 muscle cells displaying high exhaustion threshold on account that they contract and relax 20 times/min over a lifespan, making them potentially useful in cardiac regeneration strategies. Besides, it has been shown that biomaterials for stem cell delivery improve cell retention and viability in the target organ. In the present study, we aimed at developing a novel approach based on the use of poly (L-lactic acid) (PLLA) scaffolds seeded with DMs overexpressing connexin-43 (cx43), a gap junction protein that promotes inter-cell connectivity. DMs isolated from ovine diaphragm biopsies were characterized by immunohistochemistry and ability to differentiate into myotubes (MTs) and transduced with a lentiviral vector encoding cx43. After confirming cx43 expression (RT-qPCR and Western blot) and its effect on inter-cell connectivity (fluorescence recovery after photobleaching), DMs were grown on fiber-aligned or random PLLA scaffolds. DMs were successfully isolated and characterized. Cx43 mRNA and protein were overexpressed and favored inter-cell connectivity. Alignment of the scaffold fibers not only aligned but also elongated the cells, increasing the contact surface between them. This novel approach is feasible and combines the advantages of bioresorbable scaffolds as delivery method and a cell type that on account of its features may be suitable for cardiac regeneration. Future studies on animal models of myocardial infarction are needed to establish its usefulness on scar reduction and cardiac function.Fil: Giménez, Carlos Sebastián. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Medicina Traslacional, Trasplante y Bioingeniería. Fundación Favaloro. Instituto de Medicina Traslacional, Trasplante y Bioingeniería; ArgentinaFil: Locatelli, Paola. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Medicina Traslacional, Trasplante y Bioingeniería. Fundación Favaloro. Instituto de Medicina Traslacional, Trasplante y Bioingeniería; ArgentinaFil: Montini Ballarin, Florencia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mar del Plata. Instituto de Investigaciones en Ciencia y Tecnología de Materiales. Universidad Nacional de Mar del Plata. Facultad de Ingeniería. Instituto de Investigaciones en Ciencia y Tecnología de Materiales; ArgentinaFil: Orlowski, Alejandro. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Investigaciones Cardiovasculares "Dr. Horacio Eugenio Cingolani". Universidad Nacional de La Plata. Facultad de Ciencias Médicas. Centro de Investigaciones Cardiovasculares "Dr. Horacio Eugenio Cingolani"; ArgentinaFil: Dewey, Ricardo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Biotecnológicas. Instituto de Investigaciones Biotecnológicas "Dr. Raúl Alfonsín" (sede Chascomús). Universidad Nacional de San Martín. Instituto de Investigaciones Biotecnológicas. Instituto de Investigaciones Biotecnológicas "Dr. Raúl Alfonsín" (sede Chascomús); ArgentinaFil: Pena, Milagros. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Biotecnológicas. Instituto de Investigaciones Biotecnológicas "Dr. Raúl Alfonsín" (sede Chascomús). Universidad Nacional de San Martín. Instituto de Investigaciones Biotecnológicas. Instituto de Investigaciones Biotecnológicas "Dr. Raúl Alfonsín" (sede Chascomús); ArgentinaFil: Abraham, Gustavo Abel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mar del Plata. Instituto de Investigaciones en Ciencia y Tecnología de Materiales. Universidad Nacional de Mar del Plata. Facultad de Ingeniería. Instituto de Investigaciones en Ciencia y Tecnología de Materiales; ArgentinaFil: Aiello, Ernesto Alejandro. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Biotecnológicas. Instituto de Investigaciones Biotecnológicas "Dr. Raúl Alfonsín" (sede Chascomús). Universidad Nacional de San Martín. Instituto de Investigaciones Biotecnológicas. Instituto de Investigaciones Biotecnológicas "Dr. Raúl Alfonsín" (sede Chascomús); ArgentinaFil: Bauza, Maria del Rosario. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Medicina Traslacional, Trasplante y Bioingeniería. Fundación Favaloro. Instituto de Medicina Traslacional, Trasplante y Bioingeniería; ArgentinaFil: Cuniberti, Luis Alberto. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Medicina Traslacional, Trasplante y Bioingeniería. Fundación Favaloro. Instituto de Medicina Traslacional, Trasplante y Bioingeniería; ArgentinaFil: Olea, Fernanda Daniela. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Medicina Traslacional, Trasplante y Bioingeniería. Fundación Favaloro. Instituto de Medicina Traslacional, Trasplante y Bioingeniería; ArgentinaFil: Crottogini, Alberto José. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Medicina Traslacional, Trasplante y Bioingeniería. Fundación Favaloro. Instituto de Medicina Traslacional, Trasplante y Bioingeniería; Argentin