Search

Behavior skills training (BST) with ongoing coaching is an effective form of professional development that creates sustained educator practice change and improves student outcomes. We provide a model for how BST can be used to improve the implementation of evidence-based practices with both teachers and paraprofessionals, the latter of whom often do not receive professional development opportunities or coaching. We propose a model for BST with digital tools that can be used in face-to-face, hybrid, and virtual formats, which is timely given the pandemic. A vignette with a dyad of educators is used to illustrate the model and examples of fidelity and coaching forms are included. A figure of the BST process with visual supports provided to the educators is included.

Many current investigations have analysed adolescents' risky ICT behaviours (such as excessive or addictive use), but few have explored the characteristics of low-risk behaviour in this regard. This study aimed to explore the psychosocial profile of a sample of 593 Spanish adolescents aged 13 to 18 who have been categorized as low-risk ICT users. To this end, the low-risk ICT use group was calculated using the "multitasking while doing homework index" and a set of items on risky ICT behaviour. Chi-squared and t-tests were performed and a forward stepwise binary logistic regression was carried out to determine the explanatory variables for low-risk ICT use. The results showed that some 7.1% were classified as low-risk ICT users, with a higher percentage of girls. These users' profile was characterised by: lower digital self-efficacy with social networking applications; less generalized ICT use and a less dependent attitude; less extroversion and more agreeableness and conscientiousness; higher academic self-concept; having rules for ICT use at home; and less insecure and anxious attachment to parental figures. The variables that predicted the likelihood of low-risk ICT behaviour were: high academic self-concept; low perceived separation anxiety from loved ones; and high agreeableness scores. These results are useful for proposing psycho-socio-educational interventions to promote healthy ICT use.

BACKGROUND AND OBJECTIVE: The role of cytoreductive nephrectomy (CN) in the treatment of metastatic renal cell carcinoma (mRCC) has been called into question on the basis of clinical trial data from the tyrosine kinase inhibitor (TKI) era. Comparative analyses of CN for patients treated with immuno-oncology (IO) versus TKI agents are sparse. Our objective was to compare CN timing and outcomes among patients who received TKI versus IO therapy. METHODS: This was a multicenter retrospective analysis of patients who underwent CN using data from the REMARCC (Registry of Metastatic RCC) database. The cohort was divided into TKI versus IO first-line therapy groups. The primary outcome was all-cause mortality (ACM). Secondary outcomes included cancer-specific mortality (CSM). Multivariable analysis was used to identify factors predictive for ACM and CSM. The Kaplan-Meier method was used to analyze 5-yr overall survival (OS) and cancer-specific survival (CSS) with stratification by primary systemic therapy and timing in relation to CN. KEY FINDINGS AND LIMITATIONS: We analyzed data for 189 patients (148 TKI + CN, 41 IO +CN; median follow-up 23.2 mo). Multivariable analysis revealed that a greater number of metastases (hazard ratio [HR] 1.06; p = 0.015), greater primary tumor size (HR 1.10; p = 0.043), TKI receipt (HR 2.36; p = 0.015), and initiation of systemic therapy after CN (HR 1.49; p = 0.039) were associated with worse ACM. A greater number of metastases at diagnosis (HR 1.07; p = 0.011), greater primary tumor size (HR 1.12; p = 0.018), TKI receipt (HR 5.43; p = 0.004), and initiation of systemic therapy after CN (HR 2.04; p

Abstract Background Radiopharmaceuticals have been considered a special group of medicines in Europe since 1989. The use of radiopharmaceuticals that have marketing authorization should always be the first option in clinical use, however due to their special properties the availability of approved radiopharmaceuticals is limited. For this reason, they can be produced on a small scale outside the marketing authorization process. Main body The in-house radiopharmaceutical preparations represent an important source of these special medicines for routine nuclear medicine practice. However, a lack of harmonization in Member States’ regulations leads to extreme differences in the use and availability of radiopharmaceuticals across Europe. The aim of this work is to provide an overview of the different national regulatory frameworks in which Directive 2001/83/UE is adopted on the preparation of radiopharmaceuticals outside the marketing authorization track in Europe. Nine different national regulations have been studied to describe how unlicensed radiopharmaceuticals are prepared. Special attention is paid to reflect the minimum standards that these preparations should meet as well as the educational requirements to be a radiopharmacist in charge of them. Conclusion The rapid development of new radiopharmaceuticals used in radiometabolic therapy requires a common regulation that allows balance between the use and preparation of licensed and unlicensed radiopharmaceuticals. The absence of a harmonized regulation for the radiopharmaceutical small-scale preparation and the implementation of Good Manufacture Practices, leads to extreme differences in the use, quality assurance and availability of radiopharmaceuticals in Europe.

This case report describes a 23-year-old male who was incidentally diagnosed with Caroli disease while investigating symptoms of recurrent upper quadrant pain and fever. Imagining studies, including magnetic resonance cholangiography revealed the “central dot sign,” which is pathognomonic for this condition, along with cystic dilatations of the intrahepatic bile ducts and the presence of biliary stones. The diagnosis was confirmed and treatment with ursodeoxycholic acid led to a notable reduction in symptoms. This case underscores the need for further research and understanding to develop more effective diagnostic and treatment strategies. Regular follow-up remains essential for managing disease progression and preventing complications.

Abstract Background Health disparities have been highlighted among patient with prostate adenocarcinoma (PRAD) due to ethnicity. Mexican men present a more aggressive disease than other patients resulting in less favorable treatment outcome. We aimed to identify the mutational landscape which could help to reduce the health disparities among minority groups and generate the first genomics exploratory study of PRAD in Mexican patients. Methods Paraffin-embedded formalin-fixed tumoral tissue from 20 Mexican patients with early-stage PRAD treated at The Instituto Nacional de Cancerología, Mexico City from 2017 to 2019 were analyzed. Tumoral DNA was prepared for whole exome sequencing, the resulting files were mapped against h19 using BWA-MEM. Strelka2 and Lancet packages were used to identify single nucleotide variants (SNV) and insertions or deletions. FACETS was used to determine somatic copy number alterations (SCNA). Cancer Genome Interpreter web interface was used to determine the clinical relevance of variants. Results Patients were in an early clinical stage and had a mean age of 59.55 years (standard deviation [SD]: 7.1 years) with 90% of them having a Gleason Score of 7. Follow-up time was 48.50 months (SD: 32.77) with recurrences and progression in 30% and 15% of the patients, respectively. NUP98 (20%), CSMD3 (15%) and FAT1 (15%) were the genes most frequently affected by SNV; ARAF (75%) and ZNF419 (70%) were the most frequently affected by losses and gains SNCA’s. One quarter of the patients had mutations useful as biomarkers for the use of PARP inhibitors, they comprise mutations in BRCA, RAD54L and ATM. SBS05, DBS03 and ID08 were the most common mutational signatures present in this cohort. No associations with recurrence or progression were identified. Conclusions This pilot study reveals the mutational landscape of early-stage prostate adenocarcinoma in Mexican men, providing a first approach to understand the mutational patterns and actionable mutations in early prostate cancer can inform personalized treatment approaches and reduce the underrepresentation in genomic cancer studies.

Abstract Recessive dystrophic epidermolysis bullosa (RDEB) is a rare genetic disease caused by loss of function mutations in the gene coding for collagen VII (C7) due to deficient or absent C7 expression. This disrupts structural and functional skin architecture, leading to blistering, chronic wounds, inflammation, important systemic symptoms affecting the mouth, gastrointestinal tract, cornea, and kidney function, and an increased skin cancer risk. RDEB patients have an extremely poor quality of life and often die at an early age. A frequent class of mutations in RDEB is premature termination codons (PTC), which appear in homozygosity or compound heterozygosity with other mutations. RDEB has no cure and current therapies are mostly palliative. Using patient-derived keratinocytes and a library of 8273 small molecules and 20,160 microbial extracts evaluated in a phenotypic screening interrogating C7 levels, we identified three active chemical series. Two of these series had PTC readthrough activity, and one upregulated C7 mRNA, showing synergistic activity when combined with the reference readthrough molecule gentamicin. These compounds represent novel potential small molecule-based systemic strategies that could complement topical-based treatments for RDEB.

Abstract Background Imprinting disorders are rare diseases resulting from altered expression of imprinted genes, which exhibit parent-of-origin-specific expression patterns regulated through differential DNA methylation. A subgroup of patients with imprinting disorders have DNA methylation changes at multiple imprinted loci, a condition referred to as multi-locus imprinting disturbance (MLID). MLID is recognised in most but not all imprinting disorders and is also found in individuals with atypical clinical features; the presence of MLID often alters the management or prognosis of the affected person. Some cases of MLID are caused by trans-acting genetic variants, frequently not in the patients but their mothers, which have counselling implications. There is currently no consensus on the definition of MLID, clinical indications prompting testing, molecular procedures and methods for epigenetic and genetic diagnosis, recommendations for laboratory reporting, considerations for counselling, and implications for prognosis and management. The purpose of this study is thus to cover this unmet need. Methods A comprehensive literature search was conducted resulting in identification of more than 100 articles which formed the basis of discussions by two working groups focusing on clinical diagnosis (n = 12 members) and molecular testing (n = 19 members). Following eight months of preparations and regular online discussions, the experts from 11 countries compiled the preliminary documentation and determined the questions to be addressed during a face-to-face meeting which was held with the attendance of the experts together with four representatives of patient advocacy organisations. Results In light of available evidence and expert consensus, we formulated 16 propositions and 8 recommendations as interim guidance for the clinical and molecular diagnosis of MLID. Conclusions MLID is a molecular designation, and for patients with MLID and atypical phenotypes, we propose the alternative term multi-locus imprinting syndrome. Due to the intrinsic variability of MLID, the guidelines underscore the importance of involving experts from various fields to ensure a confident approach to diagnosis, counselling, and care. The authors advocate for global, collaborative efforts in both basic and translational research to tackle numerous crucial questions that currently lack answers, and suggest reconvening within the next 3–5 years to evaluate the research advancements and update this guidance as needed.

El dominio prepotente de la hegemonía de las doctrinas neoliberales está imponiendo retos educativos considerables con respecto a la consecución de los objetivos de la Agenda 2030. Nos enfrentamos a una crisis de civilización, en la que el actual modelo educativo y sus parámetros están siendo alterados, manipulados, dictados e impuestos exclusivamente por organismos relacionados con el comercio. El propio capital humano y las competencias derivan terminológicamente del neoliberalismo global; aparentemente préstamos lingüísticos heredados del mundo empresarial, en realidad son constructos caracterizados por una complejidad que implica ciertas condiciones básicas en la formación docente, directamente relacionadas con el saber, el saber hacer y principalmente con el saber ser. La Educación para la Ciudadanía Global (ECG), consagrada en la meta 4.7 del Objetivos de Desarrollo Sostenible (ODS) n.º 4 de la Agenda 2030, se convierte en un objetivo educativo, en un imperativo global, capaz de gestionar la expansión de un tipo de pedagogía mercantil que a nivel ético y de valores está desestabilizando los ecosistemas escolares globales en términos de ética y valores. El análisis de la dimensión de la competencia transformadora del profesorado en el contexto de la globalización, debe conducirnos a nuevas reflexiones relacionadas con un proceso de replanteamiento crítico de la ECG. Reflexiones localizadas que necesitan ser profundizadas y contextualizadas desde dentro, en los variados contextos educativos desde lo local a lo global, para comprender dilemas, tensiones políticas y de poder, reorientando a todos hacia el bien común. La redefinición de la gestalt educativa en el desorden global, por lo tanto, implica la valorización de la riqueza de las competencias no cognitivas de los docentes, hoy indispensables para contrarrestar la fragilidad de la pobreza educativa.

Background The benefit of patent foramen ovale closure (PFOC) ≤9 months after a cryptogenic stroke has been demonstrated in several randomised clinical trials. There is, however, insufficient data to support PFOC in non-recent cryptogenic strokes.Aims The objective of the study was to evaluate the effectiveness of PFOC in relation to the time since the patient’s most recent cryptogenic cerebrovascular event (CVE) or systemic embolism (SE).Methods We conducted a multicentre, retrospective cohort study with international participation, to assess the results of an early closure (EC,

Tunicate maize (Zea mays var. tunicata A. St. Hil) is a landrace that constitutes a fundamental aspect of the socio-cultural identity of Ixtenco, Tlaxcala (Mexico) and represents an exotic phenotype whose kernels are enclosed in leaflike glumes. Despite multiple studies conducted worldwide on plant growth-promoting-rhizobacteria (PGPR) in commercial maize varieties grown under monoculture systems, very little is known about bacteria inhabiting native maize landraces in agroecosystems, but for tunicate maize such knowledge is non-existent. This research described and profiled functional groups of culturable rhizobacteria from tunicate maize at two phenological stages (tasseling and maturity/senescence) in a polyculture system, highlighting potential PGPR for biotechnological purposes. Ninety-five rhizobacteria were isolated and molecularly identified, and their physiological activities such as plant growth promotion, production of exogenous lytic enzymes, and antagonism against fungal pathogens were determined. The culturable rhizobacterial community associated to tunicate maize comprised 42 genera, dominated by Bacillaceae, Comamonadaceae, Microbacteriaceae, Micrococcaceae, Oxalobacteraceae, Pseudomonadaceae, and Rhizobaceae families. At tasseling stage, the identified bacteria corresponded to Arthrobacter, Priestia, Herbaspirillum, Pseudomonas, and Rhizobium, and exhibited redundant capabilities for stimulating plant growth and nutrition, and inhibiting fungal phytopathogens. At maturity/senescence stage, the main genera Arthrobacter and Microbacterium displayed lytic capabilities to support mineralization process. We recorded potential novel rhizosphere functional bacteria such as Rhizobium, Sphingobium, and Arthrobacter which are not previously described associated to maize landraces, as well as their bioprospection as PGPR detected at plant phenological stages poorly explored (like maturity/senescence). This taxonomic and functional diversity was attributed to the application of agricultural practices as well as the rhizosphere effect during specific phenological stages. Results described the diversity and functionality of culturable rhizosphere bacteria from tunicate maize in polyculture systems that allowed us the detection of potential rhizobacteria for further developing of biofertilizers and biocontrollers directed as biotechnology for sustainable agriculture, and for generating strategies for conservation of native plants and their microbial genetic resources.

Background: Particulated autograft cartilage implantation is a surgical technique that has been previously described for the repair of osteochondral lesions of the talus (OLT). It uses cartilage fragments harvested from the OLT that are minced into 1-2-mm 3 fragments and then immediately reimplanted back into the chondral defect and sealed with fibrin glue during a single-stage surgery. The purpose of this study was to characterize the suitability of these minced cartilage fragments as immediate autograft for the treatment of OLTs. Methods: Thirty-one patients undergoing primary arthroscopic surgery for their OLT consented to have their loose or damaged cartilage fragments removed and analyzed in the laboratory. Harvested specimens were minced into 1- to 2-mm 3 fragments and cell count, cell density, and cell viability were determined. In addition, physical characteristics of the OLT lesion were recorded intraoperatively and analyzed including size, location, Outerbridge chondromalacia grade of the surrounding cartilage, density of underlying bone, and whether the surgeon thought the OLT was primarily hyaline or fibrocartilage. Results: An average of 419 000 cells was able to be obtained from the harvested OLT fragments. The cells were 71.2% viable after mincing. Specimens from younger patients and from lesions with worse chondromalacia adjacent to the OLT had significantly higher cell numbers. Those from lateral lesions and with worse neighboring chondromalacia had a significantly higher cell density. None of the remaining physical OLT characteristics studied seemed to significantly affect cell number or viability. Conclusion: A large number of viable cells are available for immediate autografting by removing the loose or damaged cartilage from an OLT and mincing it into 1- to 2-mm 3 fragments. These can be reimplanted into the chondral defect in a single-stage surgery. Future clinical studies are needed to determine if the addition of these live autologous cells either alone or in conjunction with other techniques significantly improves the quality of the repair tissue and clinical outcomes. Level of Evidence: Level IV, case series.

Abstract Sepsis induces intense, dynamic and heterogeneous host response modulations. Despite improvement of patient management, the risk of mortality and healthcare-associated infections remains high. Treatments to counterbalance immune response are under evaluation, but effective biomarkers are still lacking to perform patient stratification. The design of the present study was defined to alleviate the limitations of existing literature: we selected patients who survived the initial hyperinflammatory response and are still hospitalized at day 5–7 after ICU admission. Using the Immune Profiling Panel (IPP), a fully automated RT-qPCR multiplex prototype, we optimized a machine learning model combining the IPP gene expression levels for the identification of patients at high risk of worsening, a composite endpoint defined as death or secondary infection, within one week after sampling. This was done on 332 sepsis patients selected from two retrospective studies. The IPP model identified a high-risk group comprising 30% of patients, with a significant increased proportion of worsening events at day 28 compared to the low-risk group (49% vs. 28%, respectively). These preliminary results underline the potential clinical application of IPP for sepsis patient stratification in a personalized medicine perspective, that will be confirmed in a larger prospective multicenter study.

Store‐operated Ca2+ entry (SOCE) is a major mechanism for Ca2+ influx in colorectal cancer (CRC) cells. This mechanism, regulated by the filling state of the intracellular Ca2+ stores, is mediated by the endoplasmic reticulum Ca2+ sensors of the stromal interaction molecules (STIM) family [stromal interaction molecule 1 (STIM1) and STIM2] and the Ca2+‐release‐activated Ca2+ channels constituted by Orai family members, with predominance of calcium release‐activated calcium channel protein 1 (Orai1). CRC cells exhibit enhanced SOCE due to remodeling of the expression of the key SOCE molecular components. The enhanced SOCE supports a variety of cancer hallmarks. Here, we show that treatment of the colorectal adenocarcinoma cell lines HT‐29 and Caco‐2 with inanimate Lacticaseibacillus paracasei (CECT9610) and Lactiplantibacillus plantarum (CECT9608) attenuates SOCE, although no detectable effect is seen on SOCE in normal colon mucosa cells. The effect of Lacticaseibacillus paracasei and Lactiplantibacillus plantarum postbiotics was mediated by downregulation of Orai1 and STIM1, while the expression levels of Orai3 and STIM2 remained unaltered. Treatment of HT‐29 and Caco‐2 cells with inanimate Lacticaseibacillus paracasei and Lactiplantibacillus plantarum impairs in vitro migration by a mechanism likely involving attenuation of focal adhesion kinase (FAK) tyrosine phosphorylation. Cell treatment with the Orai1 inhibitor synta‐66 attenuates SOCE and prevents any further effect of Lacticaseibacillus paracasei and Lactiplantibacillus plantarum postbiotics. Together, our results indicate for the first time that Lacticaseibacillus paracasei and Lactiplantibacillus plantarum postbiotics selectively exert negative effects on Ca2+ influx through SOCE in colorectal adenocarcinoma cell lines, providing evidence for an attractive strategy against CRC.

Background and objective: The role of cytoreductive nephrectomy (CN) in the treatment of metastatic renal cell carcinoma (mRCC) has been called into question on the basis of clinical trial data from the tyrosine kinase inhibitor (TKI) era. Comparative analyses of CN for patients treated with immuno-oncology (IO) versus TKI agents are sparse. Our objective was to compare CN timing and outcomes among patients who received TKI versus IO therapy. Methods: This was a multicenter retrospective analysis of patients who underwent CN using data from the REMARCC (Registry of Metastatic RCC) database. The cohort was divided into TKI versus IO first-line therapy groups. The primary outcome was all-cause mortality (ACM). Secondary outcomes included cancer-specific mortality (CSM). Multivariable analysis was used to identify factors predictive for ACM and CSM. The Kaplan-Meier method was used to analyze 5-yr overall survival (OS) and cancer-specific survival (CSS) with stratification by primary systemic therapy and timing in relation to CN. Key findings and limitations: We analyzed data for 189 patients (148 TKI + CN, 41 IO +CN; median follow-up 23.2 mo). Multivariable analysis revealed that a greater number of metastases (hazard ratio [HR] 1.06; p = 0.015), greater primary tumor size (HR 1.10; p = 0.043), TKI receipt (HR 2.36; p = 0.015), and initiation of systemic therapy after CN (HR 1.49; p = 0.039) were associated with worse ACM. A greater number of metastases at diagnosis (HR 1.07; p = 0.011), greater primary tumor size (HR 1.12; p = 0.018), TKI receipt (HR 5.43; p = 0.004), and initiation of systemic therapy after CN (HR 2.04; p

Atrial fibrillation is the most frequent chronic arrhythmia in patients with chronic kidney disease. Oral anticoagulation with vitamin K antagonists and now direct oral anticoagulants have been and are the fundamental pillars for the prevention of thromboembolic events. However, there are no randomized clinical trials on the risk-benefit profile of oral anticoagulation in patients with chronic kidney disease stage 5 on peritoneal dialysis and there is little evidence in the literature in this population.The objective of our study was to know the prevalence, treatment and professionals involved in the management of atrial fibrillation in peritoneal dialysis patients. For this purpose, we performed a descriptive analysis through a survey sent to different peritoneal dialysis units in Spain. A total of 1,403 patients on peritoneal dialysis were included in the study, of whom 186 (13.2%) had non-valvular atrial fibrillation. In addition, the assessment of the scores of thromboembolic and bleeding risks for the indication of oral anticoagulation was mainly carried out by the cardiologist (60% of the units), as well as its prescription (cardiologist 47% or in consensus with the nephrologist 43%).In summary, patients on peritoneal dialysis have a remarkable prevalence of non-valvular atrial fibrillation. Patients frequently receive oral anticoagulation with vitamin K antagonists, as well as direct oral anticoagulants. The data obtained regarding the scores used for the assessment of thromboembolic and bleeding risk, treatment and involvement by Nephrology indicates that there is a need for training and involvement of the nephrologist in this pathology. Resumen: La fibrilación auricular es la arritmia crónica más frecuente en pacientes con enfermedad renal crónica. La anticoagulación oral con antagonistas de la vitamina K y actualmente los anticoagulantes orales de acción directa han sido y son el pilar fundamental para la prevención de eventos tromboembólicos. Sin embargo, no existen ensayos clínicos aleatorizados de su perfil riesgo-beneficio en pacientes con enfermedad renal crónica estadio 5 en diálisis peritoneal y son pocas evidencias en la literatura en esta población. El objetivo del estudio fue conocer la prevalencia, tratamiento y profesionales implicados en el manejo de la fibrilación auricular en diálisis peritoneal en nuestro entorno mediante el análisis descriptivo de una encuesta enviada a diferentes unidades de diálisis peritoneal de España. Se incluyeron en el estudio 1403 pacientes en programa de diálisis peritoneal, de los cuales 186 (13,2%) presentaban fibrilación auricular no valvular. Además, observamos que la valoración de los scores para el inicio del tratamiento anticoagulante la realizaba mayoritariamente el cardiólogo (60% de los centros), así como la prescripción de anticoagulación (cardiólogo 47% o conjuntamente con nefrólogo 43%).En conclusión, los pacientes en diálisis peritoneal presentan una notable prevalencia de fibrilación auricular no valvular. Reciben frecuentemente anticoagulación oral con antagonistas de la vitamina K, así como con anticoagulantes orales de acción directa. Los datos obtenidos respecto a las escalas utilizadas para la valoración de riesgo tromboembólico y de sangrado, tratamiento e implicación por parte de Nefrología indica que existe una necesidad de formación e implicación del nefrólogo en esta patología.