5-(carbamoylmethylene)-oxazolidin-2-ones as a promising class of heterocycles inducing apoptosis triggered by increased ROS levels and mitochondrial dysfunction in breast and cervical cancer

Oxazolidinones are antibiotics that inhibit protein synthesis by binding the 50S ribosomal subunit. Recently, numerous worldwide researches focused on their properties and possible involvement in cancer therapy have been conducted. Here, we evaluated in vitro the antiproliferative activity of some 5-(carbamoylmethylene)-oxazolidin-2-ones on MCF-7 and HeLa cells. The tested compounds displayed a wide range of cytotoxicity on these cancer cell lines, measured by MTT assay, exhibiting no cytotoxicity on non-tumorigenic MCF-10A cells. Among the nine tested derivatives, four displayed a good anticancer potential. Remarkably, OI compound showed IC50 values of 17.66 and 31.10 µM for MCF-7 and HeLa cancer cells, respectively. Furthermore, we assessed OI effect on the cell cycle by FACS analysis, highlighting a G1 phase arrest after 72 h, supported by a low expression level of Cyclin D1 protein. Moreover, mitochondrial membrane potential was reduced after OI treatment driven by high levels of ROS. These findings demonstrate that OI treatment can inhibit MCF-7 and HeLa cell proliferation and induce apoptosis by caspase-9 activation and cytochrome c release in the cytosol. Hence, 5-(carbamoylmethylene)-oxazolidin-2-ones have a promising anticancer activity, in particular, OI derivative could represent a good candidate for in vivo further studies and potential clinical use

Un mundo por comprender...cultivando mentalidades para ciudadanos globales en la primera infancia

Alineados al Proyecto Cero de la Universidad de Harvard y a la Red Latitud Nodo Sur nos embarcamos en generar un proyecto institucional, basándonos en el Programa de Pensamiento Visible y en el marco de la Enseñanza para la Comprensión. Planteamos desde la primera infancia la formación de nuestros alumnos en aptitudes que les permiten el desarrollo en el mundo, enfocándonos principalmente en el desarrollo de la competencia global como punto de partida. Generamos una propuesta, para el nivel inicial, en la cual pudimos desplegar estrategias concretas fomentando la creatividad y la innovación, para que resuelvan problemas globales actuales y futuros. A lo largo de los tres años de implementación hemos podido medir el impacto y los resultados desde la mirada de los distintos actores: alumnos, familias y docentes. Dicha experiencia es la que compartiremos y es la que el auditorio vivenciará mediante diferentes herramientas de pensamiento

Can a pathological model improve the abilities of the paretic hand in hemiplegic children? the PAM-AOT study protocol of a randomised controlled trial

Introduction Action Observation Treatment (AOT) is an innovative therapeutic approach consisting in the observation of actions followed by subsequent repetition. In children with unilateral cerebral palsy (UCP), it improves upper limb function in daily activities. The standard paradigm of AOT requires the observation of healthy models; however, it has been demonstrated that the mirror neuron system of children with UCP is more activated by observation of pathological models, showing a similar motor repertoire, than by the healthy model, suggesting that AOT based on pathological models is superior to the standard paradigm of AOT in the functional rehabilitation of the affected upper limb of children with UCP. Methods and analysis This protocol describes an active two-arm randomised controlled evaluator-blinded trial. Twenty-six children with UCP will participate in 3 weeks of intensive AOT: the experimental group will observe a pathological model, while the control group will observe a typically developed model. The primary outcome is the spontaneous use of the paretic hand, measured with the Assisting Hand Assessment. Secondary outcome measures are the Melbourne Assessment of Unilateral Upper Limb Function, the ABILHAND-Kids and the Activities Scale for Kids-performance. Assessments will be performed at baseline (T0), at the end of intensive AOT (T1), at 8-12 weeks (T2) and at 24-28 weeks (T3) after the end of intensive AOT. Ethics and dissemination The trial was approved by the Area Vasta Emilia Nord Ethics Committee (AVEN prot. n. 133117, 29 November 2018), and it was prospectively registered on ClinicalTrials.gov. The results will be submitted for publication to a peer-reviewed journal, discussed with parents of children participating in the trial and disseminated at suitable conferences. Trial registration number NCT04088994; Pre-results

Can a pathological model improve the abilities of the paretic hand in hemiplegic children? the PAM-AOT study protocol of a randomised controlled trial

Introduction Action Observation Treatment (AOT) is an innovative therapeutic approach consisting in the observation of actions followed by subsequent repetition. In children with unilateral cerebral palsy (UCP), it improves upper limb function in daily activities. The standard paradigm of AOT requires the observation of healthy models; however, it has been demonstrated that the mirror neuron system of children with UCP is more activated by observation of pathological models, showing a similar motor repertoire, than by the healthy model, suggesting that AOT based on pathological models is superior to the standard paradigm of AOT in the functional rehabilitation of the affected upper limb of children with UCP. Methods and analysis This protocol describes an active two-arm randomised controlled evaluator-blinded trial. Twenty-six children with UCP will participate in 3 weeks of intensive AOT: the experimental group will observe a pathological model, while the control group will observe a typically developed model. The primary outcome is the spontaneous use of the paretic hand, measured with the Assisting Hand Assessment. Secondary outcome measures are the Melbourne Assessment of Unilateral Upper Limb Function, the ABILHAND-Kids and the Activities Scale for Kids-performance. Assessments will be performed at baseline (T0), at the end of intensive AOT (T1), at 8-12 weeks (T2) and at 24-28 weeks (T3) after the end of intensive AOT. Ethics and dissemination The trial was approved by the Area Vasta Emilia Nord Ethics Committee (AVEN prot. n. 133117, 29 November 2018), and it was prospectively registered on ClinicalTrials.gov. The results will be submitted for publication to a peer-reviewed journal, discussed with parents of children participating in the trial and disseminated at suitable conferences. Trial registration number NCT04088994; Pre-results

High flow nasal oxygen vs. conventional oxygen therapy over respiratory oxygenation index after esophagectomy: an observational study

Background: Postoperative pulmonary complications after esophagectomy still represent a matter of concern. High flow nasal cannula (HFNC) early after major abdominal and thoracic surgery has demonstrated some advantages over conventional oxygen therapy. Data about respiratory effect of HFNC after esophagectomy is scarce. The primary aim of this study is to investigate if the early use of HFNC after esophagectomy could enhance patients' postoperative respiratory oxygenation (ROX) index and, ultimately, reduce postoperative pneumonia. Methods: In this single center retrospective study all patients undergoing to esophagectomy for cancer from May 2020 to November 2022 were evaluated. Historical cohort (HC) received postoperative oxygen supplementation with Venturi mask or nasal goggles, and a cohort was put under HFNC (HFNC cohort). ROX index, blood gas analysis, radiological atelectasis score (RAS), post-operative complications' data and information on hospital stay have been collected and analyzed. Results: Seventy-one patients were included for the final statistical analysis, 31 in the HFNC and 40 in the HC cohort. Mean age was 64±10 years and body mass index (BMI) was 26 [24-29] kg/m2. ROX index was higher in the HFNC patients than in the HC, 20.8 [16.7-25.9] vs. 14.9 [10.8-18.2] (P<0.0001). In the HFNC cohort patients, pH was higher, 7.42 [7.40-7.44] vs. 7.39 [7.37-7.43] than HC, while PaCO2 was lower in HFNC cohort compared with HC, 39 [36-41] vs. 42 [39-45] mmHg, respectively (P=0.01). RAS was similar between the two cohorts of patients, 1.5±0.98 vs. 1.4±1.04 in the HFNC and the HC cohort, respectively (P=0.611). Lower acute respiratory failure (ARF) rate was recorded among HFNC than HC cohort, 0% vs. 13% respectively, P=0.06. No difference in pneumonia frequency between two cohorts was shown. Conclusions: HFNC improved the ROX index after esophagectomy through significant respiratory rate reduction. This tool should be considered for early respiratory support after extubation in this category of patients, not only as a rescue therapy for ARF, but also to optimize early postoperative respiratory function. Whether this will improve patients' outcomes requires further large randomized controlled trials

Heterogeneity Governs 3D-Cultures of Clinically Relevant Microbial Communities

The intrinsic heterogeneity of bacterial niches should be retained in in vitrocultures to represent the complex microbial ecology. As a case study,mucin-containing hydrogels -CF-Mu3Gel - are generated by diffusion-inducedgelation, bioinspired on cystic fibrosis (CF) mucus, and a microbial nichechallenging current therapeutic strategies. At breathing frequency, CF-Mu3Gelexhibits aG′andG′′equal to 24 and 3.2 Pa, respectively. Notably, CF-Mu3Gelexhibits structural gradients with a gradual reduction of oxygen tensionacross its thickness (280–194μmol L−1). Over the culture period, a steepdecline in oxygen concentration occurs just a few millimeters below theair–mucus interface in CF-Mu3Gel, similar to those of CF airway mucus.Importantly, the distinctive features of CF-Mu3Gel significantly influencebacterial organization and antimicrobial tolerance in mono- and co-cultures ofStaphylococcus aureusandPseudomonas aeruginosathat standard culturesare unable to emulate. The antimicrobial susceptibility determined inCF-Mu3Gel corroborates the mismatch on the efficacy of antimicrobialtreatment between planktonically cultured bacteria and those in patients.With this example-based research, new light is shed on the understanding ofhow the substrate influences microbial behavior, paving the way for improvedfundamental microbiology studies and more effective drug testing anddevelopment

Colorectal Cancer Stage at Diagnosis Before vs During the COVID-19 Pandemic in Italy

IMPORTANCE Delays in screening programs and the reluctance of patients to seek medical attention because of the outbreak of SARS-CoV-2 could be associated with the risk of more advanced colorectal cancers at diagnosis. OBJECTIVE To evaluate whether the SARS-CoV-2 pandemic was associated with more advanced oncologic stage and change in clinical presentation for patients with colorectal cancer. DESIGN, SETTING, AND PARTICIPANTS This retrospective, multicenter cohort study included all 17 938 adult patients who underwent surgery for colorectal cancer from March 1, 2020, to December 31, 2021 (pandemic period), and from January 1, 2018, to February 29, 2020 (prepandemic period), in 81 participating centers in Italy, including tertiary centers and community hospitals. Follow-up was 30 days from surgery. EXPOSURES Any type of surgical procedure for colorectal cancer, including explorative surgery, palliative procedures, and atypical or segmental resections. MAIN OUTCOMES AND MEASURES The primary outcome was advanced stage of colorectal cancer at diagnosis. Secondary outcomes were distant metastasis, T4 stage, aggressive biology (defined as cancer with at least 1 of the following characteristics: signet ring cells, mucinous tumor, budding, lymphovascular invasion, perineural invasion, and lymphangitis), stenotic lesion, emergency surgery, and palliative surgery. The independent association between the pandemic period and the outcomes was assessed using multivariate random-effects logistic regression, with hospital as the cluster variable. RESULTS A total of 17 938 patients (10 007 men [55.8%]; mean [SD] age, 70.6 [12.2] years) underwent surgery for colorectal cancer: 7796 (43.5%) during the pandemic period and 10 142 (56.5%) during the prepandemic period. Logistic regression indicated that the pandemic period was significantly associated with an increased rate of advanced-stage colorectal cancer (odds ratio [OR], 1.07; 95%CI, 1.01-1.13; P = .03), aggressive biology (OR, 1.32; 95%CI, 1.15-1.53; P &lt; .001), and stenotic lesions (OR, 1.15; 95%CI, 1.01-1.31; P = .03). CONCLUSIONS AND RELEVANCE This cohort study suggests a significant association between the SARS-CoV-2 pandemic and the risk of a more advanced oncologic stage at diagnosis among patients undergoing surgery for colorectal cancer and might indicate a potential reduction of survival for these patients

Preliminary biomechanical study of triple Lutz

In artistic roller skating, there are no quantitative biomechanical studies analysing the Lutz. Therefore, the aim of this research was to analyse the kinematic of the Triple Lutz in world-class athletes. Five subjects were analysed. A motion analysis system was used to reconstruct the position of apposite markers placed on the athlete\u2019s body and on the skate. Relevant biomechanical indices representing linear and angular displacements, angular velocities were analysed in different phases of the considered movement. The pelvis centre raised on average of 25.4 cm at the take-off (range: 19.5 \u2013 34.8 cm). The mean height of the flight trajectory was of 50.5 cm (range: 42.2 \u2013 57.8 cm). The absolute distance between the pelvis centre and the right foot centre at the toe assist was 50.1 cm, whereas at the take-off it was 13.5 cm, i.e. definitely lower, with very wide oscillations between the minimum (2.6 cm) and the maximum (23.6 cm) value. The left knee and the ankle, at the toe assist, were clearly flexed (knee: 62\ub0 and ankle: 24\ub0 of dorsiflexion). Then, the knee showed the maximum extension in correspondence with the take-off of the left skate (12\ub0). In the same instant, the left ankle showed a moderate plantarflexion of 19\ub0. At the take-off of the right foot, the left knee showed a slight flexion (24\ub0), whereas the ankle showed a little flexion (21\ub0). The inclination of the trunk was more pronounced at the toe assist (37\ub0), and less marked in the following phases (end of the gliding: 32\ub0, and take-off: 28\ub0). The peak velocity varied from 4.72 m/s (recorded before the toe assist) to 4.18 m/s. Then, the velocity further reduced at the take-off of the gliding skate (2.71 m/s), and at the take-off of the jump it is 2.69 m/s. Therefore, the horizontal speed at the end of the gliding was almost equal to that at the take-off. It is possible to explain what described about the pelvis motion by analysing the lower limbs kinematics. The toe assisting leg joints showed a loading action just after the toe assist, that was very little for the hip, moderate for the knee (6\ub0), more pronounced for the ankle (21\ub0). The loading time was the shortest for the knee (0.027 s) and the longest for the ankle (0.09 s). Considering the falling time of the pelvis (0.04 s), it can be concluded that the fall is related to the loading of all the three joints of the toe assisting leg. The gliding leg, at the toe assist, was in the neutral position on the frontal plane, whereas it was markedly flexed such as the knee and the ankle. Then, the three joints made an extension movement, continuing up to the end of the gliding phase. The latero-lateral movements (adduction \u2013 abduction) of the hips were less evident in the initial phase for the gliding. Concerning the trunk movements, the subjects showed different strategies about the hip and shoulder movements in the toe assist and take-off points. The upper limbs movements in the toe assist and take-off phases were very different amongst the examined subjects. Therefore, it is not possible to individuate a reference model that can provide useful for a general analysis. In the future, a qualitative analysis of the arms movements will be carried out to understand the different strategies adopted by the various athletes

Crear cultura a través de la Educación: el rol la familia como agente clave para efectivizar el cambio

Crear cultura a través de la educación es como una de nuestras principales metas. Tenemos el firme propósito de potenciar en todos los actores, alumnos, docentes, familias, las capacidades para aprender y actuar con éxito en el mundo real, transformándonos en una comunidad de aprendizaje. Entendiendo la institución educativa como un sistema de relaciones, en el cual la familia cumple un rol fundamental de complementariedad, hemos diseñado experiencias que las integran en este proceso, con un doble propósito: Dar a conocer la propuesta pedagógica, dado que se trata de generaciones que son formadas bajo un modelo tradicional de educación, brindándoles las herramientas para acompañar y potenciar el proceso de aprendizaje de sus hijos. Empoderarlos como agentes de cambio, que permite involucrarnos en mejorar las condiciones de todos los contextos sociales de los que forman parte, impulsando las transformaciones que impactan en el seno de nuestra sociedad