Biochemical characterization and gene structure analysis of the 24-kDa glutathione transferase sigma from Taenia solium.

Taenia solium can cause human taeniasis and/or cysticercosis. The latter can in some instances cause human neurocysticercosis which is considered a priority in disease-control strategies and the prevention of mental health problems. Glutathione transferases are crucial for the establishment and long-term survival of T. solium; therefore, we structurally analyzed the 24-kDa glutathione transferase gene (Ts24gst) of T. solium and biochemically characterized its product. The gene promoter showed potential binding sites for transcription factors and xenobiotic regulatory elements. The gene consists of a transcription start site, four exons split by three introns, and a polyadenylation site. The gene architecture is conserved in cestodes. Recombinant Ts24GST (rTs24GST) was active and dimeric. Anti-rTs24GST serum showed slight cross-reactivity with human sigma-class GST. A 3D model of Ts24GST enabled identification of putative residues involved in interactions of the G-site with GSH and of the H-site with CDNB and prostaglandin D2. Furthermore, rTs24GST showed optimal activity at 45 °C and pH 9, as well as high structural stability in a wide range of temperatures and pHs. These results contribute to the better understanding of this parasite and the efforts directed to fight taeniasis/cysticercosis.

Parental Attachment and Psychosocial Adjustment in Adolescents Exposed to Marital Conflict.

(1) Background: Interparental conflict is a phenomenon that poses a serious threat not only to the quality of life of the couple but also to the father-child relationship, mother-child relationship, and well-being of adolescents. This study examined the difference in parental attachment and adjustment in adolescents exposed to marital conflict versus those not exposed to parental conflicts in low-income areas. (2) Methods: 67 adolescents involved in Child Welfare Services (CWS) in disadvantaged neighbourhoods in southern Spain were examined. The sample was split into two groups according to the exposure to marital conflict. Subsequently, differences between groups were analysed on father attachment, mother attachment, aggression, antisocial behaviour, and emotional intelligence. (3) Results: Primarily, the data showed significantly worse attachment with the father among conflict-exposed versus non-conflict-exposed adolescents. These results were not found for the attachment with the mother. Additionally, greater anger and worse stress management were found in conflict-exposed adolescents. (4) Conclusions: The results partially confirmed the spillover and compensatory hypothesis. Practical implications point out that developing preventive interventions that protect the father-adolescent attachment in situations of family conflict is recommended.

Evaluación de la gestión de calidad en la red de bibliotecas médicas de Villa Clara / Evaluation of quality management in Villa Clara medical library network

La calidad es una exigencia vigente a nivel mundial en el área de la educación, a su vez constituye un indicador fundamental para las instituciones educativas, sujetas a proporcionar un servicio de excelencia. Por ello resulta necesario evaluar la gestión de calidad en las bibliotecas médicas de Villa Clara, de manera tal que se contribuya al mejoramiento de su funcionamiento y lograr un mayor nivel de satisfacción de las necesidades informativas de sus usuarios. Se tomaron como referentes teóricos el modelo de evaluación de bibliotecas universitarias cubanas, y los documentos normativos y teórico-metodológicos del Centro Nacional de Información sobre la temática.

Quality is a worldwide requirement in the education area, and at the same time it is a fundamental indicator for educational institutions which are subjected to provide a service of excellence. For this reason, evaluating the quality management of medical libraries in Villa Clara is a necessity, in order to contribute to the improvement of their functioning and to achieve a higher level of satisfaction of their users' information needs. The evaluation model for Cuban university libraries and the normative, theoretical and methodological documents of the National Information Center of Medical Sciences regarding this subject were taken as theoretical references.

Differential Protein Expression of Taenia crassiceps ORF Strain in the Murine Cysticercosis Model Using Resistant (C57BL/6) Mice.

A cysticercosis model of Taenia crassiceps ORF strain in susceptible BALB/c mice revealed a Th2 response after 4 weeks, allowing for the growth of the parasite, whereas resistant C57BL/6 mice developed a sustained Th1 response, limiting parasitic growth. However, little is known about how cysticerci respond to an immunological environment in resistant mice. Here, we show that the Th1 response, during infection in resistant C57BL/6 mice, lasted up to 8 weeks and kept parasitemia low. Proteomics analysis of parasites during this Th1 environment showed an average of 128 expressed proteins; we chose 15 proteins whose differential expression varied between 70 and 100%. A total of 11 proteins were identified that formed a group whose expression increased at 4 weeks and decreased at 8 weeks, and another group with proteins whose expression was high at 2 weeks and decreased at 8 weeks. These identified proteins participate in tissue repair, immunoregulation and parasite establishment. This suggests that T. crassiceps cysticerci in mice resistant under the Th1 environment express proteins that control damage and help to establish a parasite in the host. These proteins could be targets for drugs or vaccine development.

Romani Girls Matter: Developing a Participatory Action Research Protocol for Reproductive Justice.

Despite the last few decades' advances towards social and gender justice, reproductive decisions are still a source of oppression for many European Romani women and girls. This protocol aims to propose a model to empower Romani women and girls' reproductive decisions, inspired by Reproductive Justice-the recognition of women and girls' ability to make safe and free decisions about their bodies and reproduction. Through Participatory Action Research, 15-20 Romani girls and their families, two Romani platforms, and key agents from a rural and an urban context in Spain will participate. They will (1) contextualize Romani women and girls' inequities, (2) build partnerships, (3) implement Photovoice and advocate for their gender rights, and (4) assess the initiative's related changes, using self-evaluation techniques. Qualitative and quantitative indicators will be collected to assess impacts among participants, while tailoring and assuring the quality of the actions. Expected outcomes include the creation and consolidation of new social networks, and the promotion of Romani women and girls' leadership. For this, Romani organizations must be transformed into empowering settings for their communities, spaces where Romani women and girls assume responsibility of the initiatives, being these tailored to their real needs and interests, and guaranteeing transformative social changes.

Evaluation of Programmes under the Positive Parenting Initiative in Spain:Introduction to the Special Issue / La evaluación de programas bajo la iniciativa de la parentalidad positiva en España: introducción al número especial

The prevention science has endorsed standards for evidence related to research on programme evaluation. However, some controversies persist regarding its application in the provision of family support under the European Positive Parenting initiative. This Special Issue aims to map the expansion of preventive family support programmes in Spain and to contrast the quality of the evidence against the prevention standards according with the European Family Support Network. Members of the Spanish Family Support Network made up of entities in several sectors identified 57 programmes implemented in Spain and filled in a formative evaluation sheet for each programme. The articles in this issue analysed the results of four main aspects in all programmes: description, implementation, evaluation, and impact/sustainability. The findings will inform the scope and variety of support provided and the quality of programmes in Spain, providing guidelines for improvement and addressing challenges to reinforce quality assurance in child and family services.(AU)

La ciencia de la prevención avala los estándares de evidencia relativos a la investigación en evaluación de programas. Sin embargo, hay aún controversia en cuanto a su aplicación a la prestación de apoyo familiar bajo la iniciativa europea de la parentalidad positiva. El número especial tiene por objeto mapear la extensión de los programas preventivos de apoyo familiar en España y comparar la calidad de las pruebas con los estándares de prevención de la Red Europea de Apoyo Familiar. Los miembros de la Red Española de Apoyo Familiar, formada por entidades de varios sectores, han identificado 57 programas que se utilizan en España y cumplimentado una ficha de evaluación formativa para cada programa. Los artículos de este número analizan los resultados de cuatro aspectos principales de todos los programas: descripción, implementación, evaluación e impacto/sostenibilidad. Los resultados describen el panorama y variedad del apoyo brindado y la calidad de los programas en España, proporcionando orientación sobre mejora y abordando los desafíos para reforzar la garantía de calidad en los servicios para la infancia, adolescencia y familias.(AU)

The Evaluation of Family Support Programmes in Spain. An Analysis of their Quality Standards / La evaluación de los programas de apoyo familiar en España. Un análisis de sus estándares de calidad

Since the well-known publication of the Society for Prevention Research about standards for evidence related to research on prevention interventions, a rigorous evaluation is considered one of the main requirements for evidence-based programmes. Despite their importance, many programmes do not include evaluation designs that meet the most widely agreed quality standards. The aim of this study was to examine the evaluation processes of fifty-seven Spanish programmes identified in the context of the COST European Family Support Network. The obtained results provide a fairly positive picture of the quality of programme evaluation standards, although more designs that include a control group, follow-up evaluations assessing long-term effects, and the evaluation of child and indirect outcomes are needed. The results are discussed from a comprehensive and plural perspective of evaluation which, in addition to methodological rigor, considers the usefulness, feasibility, and ethical rigor of evaluation research.(AU)

A partir de las propuestas de la Society for Prevention Research sobre los estándares de evidencia necesarios para las intervenciones preventivas, contar con una evaluación rigurosa se considera como uno de los principales requisitos de los programas basados en la evidencia. A pesar de su importancia, muchos programas de apoyo familiar no cuentan con diseños de evaluación que cumplan con los estándares de calidad más consensuados. El objetivo de este artículo fue analizar los procesos de evaluación de cincuenta y siete programas españoles identificados en el marco del proyecto COST European Family Support Network. Los resultados obtenidos muestran una imagen bastante positiva de los estándares de calidad que caracterizan la evaluación de los programas, aunque es necesario ampliar el número de diseños que incluyan grupos de comparación, que contemplen medidas de los efectos en el bienestar infantil y que lleven a cabo evaluaciones de seguimiento para medir los efectos a largo plazo de las intervenciones. Se analizan los resultados desde un enfoque plural de la evaluación, que además del rigor metodológico considera la necesidad de tener en cuenta la utilidad, la viabilidad y el rigor ético de las investigaciones de evaluación.(AU)

Examining the Relationship between Dietary Intake, Socioeconomic Status, and Systolic Blood Pressure of Adults on Hemodialysis in Quito, Ecuador.

Background: In Ecuador, the number of adults on hemodialysis (HD) continues to rise. Currently, the effect dietary habits and socioeconomic status (SES) have on blood pressure is not known for those on HD. Objectives: The objectives of this study focused on adults on HD in Quito, Ecuador to 1) assess the relationship between dietary intake and SES; 2) compare dietary intake to the Kidney Disease Outcomes Quality Initiative (KDOQI) guidelines; and 3) explore the relationship between dietary intake and systolic blood pressure. Methods: This cross-sectional study was conducted at the dialysis center within Eugenio Espejo Specialties Hospital in Quito, Ecuador between May and June 2022 among 50 adults on HD. Three 24-h recalls were used to determine average dietary intake and the 25-item Instituto Nacional de Estadística y Censos-Stratification of SES was used to determine SES. Electrolytes and 2 blood pressure readings were collected. Qualitative narrative data analysis was performed to identify themes using NVivo v12. T-tests of independence, simple, and multiple linear regressions using age and sex as confounders were conducted using R and a P < 0.05 was deemed as statistically significant. Results: On an average, 76% of participants consumed <25 kcal/kg body weight energy and 64% consumed <1 g protein/kg body weight. Participants consumed less energy and protein compared with the KDOQI guidelines (P < 0.05). Positive relationships were observed with potassium and blood pressure (ß = 0.020, P < 0.05) and SES with energy, protein, and phosphorus (P < 0.05). Themes that were identified as contributing to dietary intake were limited knowledge, lack of consistency with dietary information, and limited appetite. Conclusions: Findings from this study indicate that the focus should be on improving energy and protein intake for this population.

Multiplexed cellular profiling identifies an organoselenium compound as an inhibitor of CRM1-mediated nuclear export.

Chromosomal region maintenance 1 (CRM1 also known as Xpo1 and exportin-1) is the receptor for the nuclear export controlling the intracellular localization and function of many cellular and viral proteins that play a crucial role in viral infections and cancer. The inhibition of CRM1 has emerged as a promising therapeutic approach to interfere with the lifecycle of many viruses, for the treatment of cancer, and to overcome therapy resistance. Recently, selinexor has been approved as the first CRM1 inhibitor for the treatment of multiple myeloma, providing proof of concept for this therapeutic option with a new mode of action. However, selinexor is associated with dose-limiting toxicity and hence, the discovery of alternative small molecule leads that could be developed as less toxic anticancer and antiviral therapeutics will have a significant impact in the clinic. Here, we report a CRM1 inhibitor discovery platform. The development of this platform includes reporter cell lines that monitor CRM1 activity by using red fluorescent protein or green fluorescent protein-labeled HIV-1 Rev protein with a strong heterologous nuclear export signal. Simultaneously, the intracellular localization of other proteins, to be interrogated for their capacity to undergo CRM1-mediated export, can be followed by co-culturing stable cell lines expressing fluorescent fusion proteins. We used this platform to interrogate the mode of nuclear export of several proteins, including PDK1, p110α, STAT5A, FOXO1, 3, 4 and TRIB2, and to screen a compound collection. We show that while p110α partially relies on CRM1-dependent nuclear export, TRIB2 is exported from the nucleus in a CRM1-independent manner. Compound screening revealed the striking activity of an organoselenium compound on the CRM1 nuclear export receptor.

Prevalence and global estimates of unsafe listening practices in adolescents and young adults: a systematic review and meta-analysis.

INTRODUCTION: This study aimed to determine the prevalence of unsafe listening practices from exposure to personal listening devices (PLDs) and loud entertainment venues in individuals aged 12-34 years, and to estimate the number of young people who could be at risk of hearing loss from unsafe listening worldwide. METHODS: We conducted a systematic review and meta-analysis to estimate the prevalence of unsafe listening practices from PLDs and loud entertainment venues. We searched three databases for peer-reviewed articles published between 2000 and 2021 that reported unsafe listening practices in individuals aged 12-34 years. Pooled prevalence estimates (95% CI) of exposed populations were calculated using random effects models or ascertained from the systematic review. The number of young people who could be at risk of hearing loss worldwide was estimated from the estimated global population aged 12-34 years, and best estimates of exposure to unsafe listening ascertained from this review. RESULTS: Thirty-three studies (corresponding to data from 35 records and 19 046 individuals) were included; 17 and 18 records focused on PLD use and loud entertainment venues, respectively. The pooled prevalence estimate of exposure to unsafe listening from PLDs was 23.81% (95% CI 18.99% to 29.42%). There was limited certainty (p>0.50) in our pooled prevalence estimate for loud entertainment venues. Thus, we fitted a model as a function of intensity thresholds and exposure duration to identify the prevalence estimate as 48.20%. The global estimated number of young people who could be at risk of hearing loss from exposure to unsafe listening practices ranged from 0.67 to 1.35 billion. CONCLUSIONS: Unsafe listening practices are highly prevalent worldwide and may place over 1 billion young people at risk of hearing loss. There is an urgent need to prioritise policy focused on safe listening. The World Health Organization provides comprehensive materials to aid in policy development and implementation.

Value of Music and Nitrous Oxide for Pain Control during Extracorporeal Shock Wave Lithotripsy (ESWL).

OBJECTIVES: To compare the efficacy of 4 different analgesic regimens that include music and nitrous oxide during the treatment of renal lithiasis with ambulatory extracorporeal shock wave lithotripsy (ESWL). MATERIALS AND METHODS: A single-centre, longitudinal, prospective, randomized, open and parallel group study was conducted. Patients with renal lithiasis were included and were randomized to Group A (basal analgesia: midazolam (1 mg), fentanyl (0.05 mg) and dexketoprofen (50 mg)), Group B (basal analgesia and nitrous oxide), Group C (basal analgesia and music) and Group D (basal analgesia, nitrous oxide and music). For the measurement of pain, a visual analogue scale ranging from 0 (no pain) to 100 (maximum pain imaginable) was used. Patient satisfaction was assessed using a Likert questionnaire. The epidemiological data of the patients in terms of lithiasis, previous clinical and ESWL sessions, and pain measured with the VAS before, during (maximum) at the end of the session and at discharge were recorded. Data on complications were also collected, as was the patients' subjective evaluation of the treatment and their satisfaction. The ESWL procedure was performed with a Storz Modulith SLX-F2® lithotripter. A maximum of 4000 waves were applied at a frequency of 1.5 Hz. RESULTS: Eighty patients were included (20 per group). None of the analgesia guidelines proved to be superior to the others for pain control during the ESWL session. Patients younger than 50 years had significantly higher values for the maximum VAS. Only 13.75% of patients required rescue analgesia. A total of 77.5% described their experience as good, very good or excellent, regardless of the assigned group. CONCLUSIONS: The addition of nitrous oxide and/or music did not result in a statistically significant improvement over the basal analgesia regimen of midazolam, fentanyl and dexketoprofen; however, the degree of patient satisfaction was very high.

Prevalence and associated risk factors of chronic kidney disease: A case study within SIME clinics in Quito, Ecuador 2019-2021.

Background: Ecuador has been experiencing an epidemiological transition due to its demographic and lifestyle changes, where non-communicable diseases are the leading cause of death, including chronic kidney disease (CKD). Quito, Ecuador's capital city, is one of the cities burdened by CKD, yet it is unknown the factors that contribute to the rising incidence of this disease. The purpose of this study was to estimate the prevalence of CKD among non-institutionalized adults in Quito between 2019 and 2021, and to examine its associations with various risk factors. Methods: For the analysis of prevalence, the Kidney Disease: Improving Global Outcomes guidelines were used, where an estimated glomerular filtration rate (eGFR) of < 60 ml/min/1.73 m2 was counted as a presumed case of CKD. The Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation was used to calculate eGFR. Multiple linear regression models were used to determined associations between blood pressure, blood glucose, sex, and zone with eGFR. A t-test of independence was used to determine difference in means between sex and zone and eGFR. Results: A prevalence of 7.2% was found, in which almost 45% of the participants were classified within stages 2-4 of this disease. The risk factors that were significantly associated with eGFR were systolic blood pressure (ß = -0.43, p < 0.001), sex, and zone (p < 0.001). Conclusions: Overall a high prevalence of CKD was found among adults who visited SIME clinics in Quito. Associations between main risk factors and eGFR were found, yet further research is needed to explore CKD in Ecuador and its main cities.

mTORC2 Is the Major Second Layer Kinase Negatively Regulating FOXO3 Activity.

Forkhead box O (FOXO) proteins are transcription factors involved in cancer and aging and their pharmacological manipulation could be beneficial for the treatment of cancer and healthy aging. FOXO proteins are mainly regulated by post-translational modifications including phosphorylation, acetylation and ubiquitination. As these modifications are reversible, activation and inactivation of FOXO factors is attainable through pharmacological treatment. One major regulatory input of FOXO signaling is mediated by protein kinases. Here, we use specific inhibitors against different kinases including PI3K, mTOR, MEK and ALK, and other receptor tyrosine kinases (RTKs) to determine their effect on FOXO3 activity. While we show that inhibition of PI3K efficiently drives FOXO3 into the cell nucleus, the dual PI3K/mTOR inhibitors dactolisib and PI-103 induce nuclear FOXO translocation more potently than the PI3Kδ inhibitor idelalisib. Furthermore, specific inhibition of mTOR kinase activity affecting both mTORC1 and mTORC2 potently induced nuclear translocation of FOXO3, while rapamycin, which specifically inhibits the mTORC1, failed to affect FOXO3. Interestingly, inhibition of the MAPK pathway had no effect on the localization of FOXO3 and upstream RTK inhibition only weakly induced nuclear FOXO3. We also measured the effect of the test compounds on the phosphorylation status of AKT, FOXO3 and ERK, on FOXO-dependent transcriptional activity and on the subcellular localization of other FOXO isoforms. We conclude that mTORC2 is the most important second layer kinase negatively regulating FOXO activity.

Value of Music and Nitrous Oxide for Pain Control during Extracorporeal Shock Wave Lithotripsy (ESWL)

Objectives: To compare the efficacy of 4 different analgesic regimens that include music and nitrous oxide during the treatment of renal lithiasis with ambulatory extracorporeal shock wave lithotripsy (ESWL). Materials and Methods: A single-centre, longitudinal, prospective, randomized, open and parallel group study was conducted. Patients with renal lithiasis were included and were randomized to Group A (basal analgesia: midazolam (1 mg), fentanyl (0.05 mg) and dexketoprofen (50 mg)), Group B (basal analgesia and nitrous oxide), Group C (basal analgesia and music) and Group D (basal analgesia, nitrous oxide and music). For the measurement of pain, a visual analogue scale ranging from 0 (no pain) to 100 (maximum pain imaginable) was used. Patient satisfaction was assessed using a Likert questionnaire. The epidemiological data of the patients in terms of lithiasis, previous clinical and ESWL sessions, and pain measured with the VAS before, during (maximum) at the end of the session and at discharge were recorded. Data on complications were also collected, as was the patients’ subjective evaluation of the treatment and their satisfaction. The ESWL procedure was performed with a Storz Modulith SLX-F2® lithotripter. A maximum of 4000 waves were applied at a frequency of 1.5 Hz. Results: Eighty patients were included (20 per group). None of the analgesia guidelines proved to be superior to the others for pain control during the ESWL session. Patients younger than 50 years had significantly higher values for the maximum VAS. Only 13.75% of patients required rescue analgesia. A total of 77.5% described their experience as good, very good or excellent, regardless of the assigned group. Conclusions: The addition of nitrous oxide and/or music did not result in a statistically significant improvement over the basal analgesia regimen of midazolam, fentanyl and dexketoprofen; however, the degree of patient satisfaction was very high (AU)

Evaluation of recombinant glutathione transferase 26 kDa, thioredoxin-1, and endophilin B1 of Taenia solium in the diagnosis of human neurocysticercosis.

Neurocysticercosis caused by Taenia solium larvae is a neglected disease that persists in several countries, including Mexico, and causes a high disability-adjusted life year burden. Neuroimaging tools such as computed tomography and magnetic resonance imaging are the most efficient for its detection, but low availability and high costs in most endemic regions limit their use. Serological methods such as lentil lectin-purified glycoprotein enzyme-linked immunoelectrotransfer blot antibody detection and monoclonal antibody-based enzyme-linked immunosorbent assays for HP10 antigen detection have been useful in supporting the diagnosis of this disease. We evaluated three T. solium recombinant antigens: glutathione transferase of 26 kDa (Ts26GST); thioredoxin-1 (TsTrx-1), and endophilin B1 (TsMEndoB1) by EITB. These are antigenic proteins antigenic, abundant in excretion/secretion products of the parasite, and do not cross-react with homologous host proteins. Ts26GST and TsTrx-1 showed sensitivity of 79 and 88%, specificity of 86 and 97%, PPV of 83 and 97% and NPV of 82 and 91%, respectively, for neurocysticercosis diagnosis. The recombinant antigens allowed the diagnosis of 70% (Ts26GST) and 80% (TsTrx-1) of patients having only one cysticercus. Further studies on specific regions of these proteins could improve T. solium diagnostics.

Prognostic factors of trochanteric bursitis in surgical-staged patients: a prospective study.

BACKGROUND: Trochanteric bursitis or greater trochanteric pain syndrome is a common disorder and frequent cause of lateral hip pain. It can lead to severe functional impairment with increase morbidity and poor quality of life.The purpose of the current study was to identify and evaluate relationship between health-related factors, as prognostic indicators, and clinical outcomes. METHODS: A single-centre, prospective study was conducted and 60 patients (62 hips) were included with a minimum 12 months of follow-up. Clinical outcomes were evaluated using Hip Outcome Scale, Single Assessment Numeric Evaluation and Visual Analogue Scale. Radiological assessments and health-related factors were documented in an attempt to understand their validity as predictors of clinical outcomes. Complications and recurrence rates were also analyzed. RESULTS: Univariate model revealed that an increased BMI (p = 0.001; OR = 1.05; 95% CI, 1.02-1.07); number of previous corticosteroid infiltrations (p = 0.001; OR = 1.28, 95% CI, 1.11-1.48); longer time from symptom onset to surgery (p = 0.001; OR = 1.19; 95% CI, 1.12-1.28); smoker status (p = 0.001; OR 11.2; 95% CI, 3.30-44.2); and the presence of prior lumbosacral fusion (LSF) (p = 0.001; OR 13.8; 95% CI, 2.96-101); were prognostic factors predisposing for poor clinical outcomes.Among prognostic health-related factors were medical comorbidities such as emotional distress (p < 0.001; OR 26.1; 95% CI, 5.71-192); fibromyalgia (p = 0.026; OR 3.56; 95% CI, 1.16-11.7); and hyporthyroidism (p = 0.005, OR = 6.55, 95% CI, 1.73-28.7). CONCLUSIONS: Better overall physical function was predicted by lower number of corticosteroid infiltrations, shorter time span from symptom onset to surgery, non-smoker status and the absence of prior lumbosacral fusion. Obesity, smoking, the presence of emotional distress, fibromyalgia and hypothyroidism seem to increase the risk of poor clinical outcomes. A proper selection and/or correction of modifiable prognostic factors could reduce the incidence of endoscopic treatment failure and, as a consequence, improve patient outcomes and quality of life. However, future efforts should focus on experimental and randomised studies to fully determine these associations.

Screening Health-Promoting Compounds for Their Capacity to Induce the Activity of FOXO3.

Several chemical compounds including natural products have been suggested as being effective against age-related diseases or as beneficial for a healthy life. On the other hand, forkhead box O (FOXO) proteins are emerging as key cellular components associated with extreme human longevity. FOXO proteins are mainly regulated by posttranslational modifications and as these modifications are reversible, activation and inactivation of FOXO are attainable through pharmacological treatment. Here, we questioned whether a panel of compounds with known health-beneficial properties has the capacity to induce the activity of FOXO factors. We show that resveratrol, a phytoalexin present in grapes and other food products, the amide alkaloid piperlongumine found in the fruit of the long pepper, and the plant-derived ß-carboline compound harmine induced nuclear translocation of FOXO3. We also show that piperlongumine and harmine but not resveratrol activate FOXO-dependent transcription. We determined the half maximal effective concentration (EC50) values for resveratrol, piperlongumine, and harmine for FOXO translocation, and analyzed their inhibitory impact on chromosomal maintenance 1 (CRM1)-mediated nuclear export and the production of reactive oxygen species (ROS). We also used chemical biology approach and Western blot analysis to explore the underlying molecular mechanisms. We show that harmine, piperlongumine, and resveratrol activate FOXO3 independently of phosphoinositide 3-kinase (PI3K)/AKT signaling and the CRM1-mediated nuclear export. The effect of harmine on FOXO3 activity is at least partially mediated through the inhibition of dual-specificity tyrosine (Y) phosphorylationregulated kinase 1A (DYRK1A) and can be reverted by the inhibition of sirtuins (SIRTs).

Unravelling data for rapid evidence-based response to COVID-19: a summary of the unCoVer protocol.

INTRODUCTION: unCoVer-Unravelling data for rapid evidence-based response to COVID-19-is a Horizon 2020-funded network of 29 partners from 18 countries capable of collecting and using real-world data (RWD) derived from the response and provision of care to patients with COVID-19 by health systems across Europe and elsewhere. unCoVer aims to exploit the full potential of this information to rapidly address clinical and epidemiological research questions arising from the evolving pandemic. METHODS AND ANALYSIS: From the onset of the COVID-19 pandemic, partners are gathering RWD from electronic health records currently including information from over 22 000 hospitalised patients with COVID-19, and national surveillance and screening data, and registries with over 1 900 000 COVID-19 cases across Europe, with continuous updates. These heterogeneous datasets will be described, harmonised and integrated into a multi-user data repository operated through Opal-DataSHIELD, an interoperable open-source server application. Federated data analyses, without sharing or disclosing any individual-level data, will be performed with the objective to reveal patients' baseline characteristics, biomarkers, determinants of COVID-19 prognosis, safety and effectiveness of treatments, and potential strategies against COVID-19, as well as epidemiological patterns. These analyses will complement evidence from efficacy/safety clinical trials, where vulnerable, more complex/heterogeneous populations and those most at risk of severe COVID-19 are often excluded. ETHICS AND DISSEMINATION: After strict ethical considerations, databases will be available through a federated data analysis platform that allows processing of available COVID-19 RWD without disclosing identification information to analysts and limiting output to data aggregates. Dissemination of unCoVer's activities will be related to the access and use of dissimilar RWD, as well as the results generated by the pooled analyses. Dissemination will include training and educational activities, scientific publications and conference communications.

Protocol for the Implementation and Evaluation of a Mindfulness-Based Intervention for Caregivers of Children with Mental Disorders in a Clinical Setting.

Being a parent is complicated in typical circumstances, with a great psychological impact as well as feelings and experiences of great intensity. This impact is greater in families in vulnerable situations, such as those with children with mental health problems, receiving treatment in a clinical setting. Due to these challenges, parenting in these circumstances is often accompanied by experiences of stress. An approach that has shown evidence of effectiveness in mitigating the negative impact of stress is mindfulness-based interventions, including the Mindfulness-Based Stress Reduction intervention program. The Mindfulness-Based Stress Reduction intervention program is designed as a psychoeducational, instructional, multimodal, and structured program whose main objective is to provide strategies for the management, coping, and awareness of stress in order to reduce it. In this paper, a protocol for the implementation and evaluation of the original Mindfulness-Based Stress Reduction intervention program with the added positive parenting component is presented, in order to systematize the incorporation of a parenting component in the Mindfulness-Based Stress Reduction intervention program, analyze its effectiveness for parents whose children have mental health problems (in terms of stress, mindfulness, emotional intelligence, general health, and parental role), explore the mechanisms of change operating in this intervention as perceived by the participants, and examine the application of acquired strategies to daily life.

Efficacy and safety of intramuscular administration of allogeneic adipose tissue derived and expanded mesenchymal stromal cells in diabetic patients with critical limb ischemia with no possibility of revascularization: study protocol for a randomized controlled double-blind phase II clinical trial (The NOMA Trial).

BACKGROUND: Chronic lower limb ischemia develops earlier and more frequently in patients with type 2 diabetes mellitus. Diabetes remains the main cause of lower-extremity non-traumatic amputations. Current medical treatment, based on antiplatelet therapy and statins, has demonstrated deficient improvement of the disease. In recent years, research has shown that it is possible to improve tissue perfusion through therapeutic angiogenesis. Both in animal models and humans, it has been shown that cell therapy can induce therapeutic angiogenesis, making mesenchymal stromal cell-based therapy one of the most promising therapeutic alternatives. The aim of this study is to evaluate the feasibility, safety, and efficacy of cell therapy based on mesenchymal stromal cells derived from adipose tissue intramuscular administration to patients with type 2 diabetes mellitus with critical limb ischemia and without possibility of revascularization. METHODS: A multicenter, randomized double-blind, placebo-controlled trial has been designed. Ninety eligible patients will be randomly assigned at a ratio 1:1:1 to one of the following: control group (n = 30), low-cell dose treatment group (n = 30), and high-cell dose treatment group (n = 30). Treatment will be administered in a single-dose way and patients will be followed for 12 months. Primary outcome (safety) will be evaluated by measuring the rate of adverse events within the study period. Secondary outcomes (efficacy) will be measured by assessing clinical, analytical, and imaging-test parameters. Tertiary outcome (quality of life) will be evaluated with SF-12 and VascuQol-6 scales. DISCUSSION: Chronic lower limb ischemia has limited therapeutic options and constitutes a public health problem in both developed and underdeveloped countries. Given that the current treatment is not established in daily clinical practice, it is essential to provide evidence-based data that allow taking a step forward in its clinical development. Also, the multidisciplinary coordination exercise needed to develop this clinical trial protocol will undoubtfully be useful to conduct academic clinical trials in the field of cell therapy in the near future. TRIAL REGISTRATION: ClinicalTrials.gov NCT04466007 . Registered on January 07, 2020. All items from the World Health Organization Trial Registration Data Set are included within the body of the protocol.