Dim light, sleep tight, and wake up bright:Sleep optimization in athletes by means of light regulation

Despite an elevated recovery need, research indicates that athletes often exhibit relatively poor sleep. Timing and consolidation of sleep is driven by the circadian system, which requires periodic light–dark exposure for stable entrainment to the 24-hour day, but is often disturbed due to underexposure to light in the morning (e.g. low-level indoor lighting) and overexposure to light in the evening (e.g. environmental and screen-light). This study examined whether combining fixed sleep schedules with light regulation leads to more consolidated sleep. Morning light exposure was increased using light-emitting goggles, whereas evening light exposure was reduced using amber-lens glasses. Using a within-subject crossover design, twenty-six athletes (14 female, 12 male) were randomly assigned to start the intervention with the light-regulation-week or the no light-regulation-week. Sleep was monitored by means of sleep diaries and actigraphy. Due to low protocol adherence regarding the fixed sleep-wake schedules, two datasets were constructed; one including athletes who kept a strict sleep-wake schedule (N = 8), and one that also included athletes with a more lenient sleep-wake schedule (N = 25). In case of a lenient sleep-wake schedule, light regulation improved self-reported sleep onset latency (Δ SOL = 8 min). This effect was stronger (Δ SOL = 17 min) and complemented by enhanced subjective sleep quality in case of a strict sleep-wake schedule. None of the actigraphy-based estimates differed significantly between conditions. To conclude, light regulation may be considered a potentially effective strategy to improve subjective sleep, but less obtrusive methods should be explored to increase protocol compliance.</p

Patient-derived head and neck cancer organoids allow treatment stratification and serve as a tool for biomarker validation and identification

Background: Organoids are in vitro three-dimensional structures that can be grown from patient tissue. Head and neck cancer (HNC) is a collective term used for multiple tumor types including squamous cell carcinomas and salivary gland adenocarcinomas.Methods: Organoids were established from HNC patient tumor tissue and characterized using immunohistochemistry and DNA sequencing. Organoids were exposed to chemo- and radiotherapy and a panel of targeted agents. Organoid response was correlated with patient clinical response. CRISPR-Cas9-based gene editing of organoids was applied for biomarker validation.Findings: A HNC biobank consisting of 110 models, including 65 tumor models, was generated. Organoids retained DNA alterations found in HNC. Comparison of organoid and patient response to radiotherapy (primary [n = 6] and adjuvant [n = 15]) indicated potential for guiding treatment options in the adjuvant setting. In organoids, the radio-sensitizing potential of cisplatin and carboplatin could be validated. However, cetuximab conveyed radioprotection in most models. HNC-targeted treatments were tested on 31 models, indicating possible novel treatment options with the potential for treatment stratification in the future. Activating PIK3CA mutations did not predict alpelisib response in organoids. Protein arginine methyltransferase 5 (PRMT5) inhibitors were identified as a potential treatment option for cyclin-dependent kinase inhibitor 2A (CDKN2A) null HNC.Conclusions: Organoids hold potential as a diagnostic tool in personalized medicine for HNC. In vitro organoid response to radiotherapy (RT) showed a trend that mimics clinical response, indicating the predictive potential of patient-derived organoids. Moreover, organoids could be used for biomarker discovery and validation.</p

Patient-derived head and neck cancer organoids allow treatment stratification and serve as a tool for biomarker validation and identification

Background: Organoids are in vitro three-dimensional structures that can be grown from patient tissue. Head and neck cancer (HNC) is a collective term used for multiple tumor types including squamous cell carcinomas and salivary gland adenocarcinomas. Methods: Organoids were established from HNC patient tumor tissue and characterized using immunohistochemistry and DNA sequencing. Organoids were exposed to chemo- and radiotherapy and a panel of targeted agents. Organoid response was correlated with patient clinical response. CRISPR-Cas9-based gene editing of organoids was applied for biomarker validation. Findings: A HNC biobank consisting of 110 models, including 65 tumor models, was generated. Organoids retained DNA alterations found in HNC. Comparison of organoid and patient response to radiotherapy (primary [n = 6] and adjuvant [n = 15]) indicated potential for guiding treatment options in the adjuvant setting. In organoids, the radio-sensitizing potential of cisplatin and carboplatin could be validated. However, cetuximab conveyed radioprotection in most models. HNC-targeted treatments were tested on 31 models, indicating possible novel treatment options with the potential for treatment stratification in the future. Activating PIK3CA mutations did not predict alpelisib response in organoids. Protein arginine methyltransferase 5 (PRMT5) inhibitors were identified as a potential treatment option for cyclin-dependent kinase inhibitor 2A (CDKN2A) null HNC. Conclusions: Organoids hold potential as a diagnostic tool in personalized medicine for HNC. In vitro organoid response to radiotherapy (RT) showed a trend that mimics clinical response, indicating the predictive potential of patient-derived organoids. Moreover, organoids could be used for biomarker discovery and validation

Discutindo a educação ambiental no cotidiano escolar: desenvolvimento de projetos na escola formação inicial e continuada de professores

A presente pesquisa buscou discutir como a Educação Ambiental (EA) vem sendo trabalhada, no Ensino Fundamental e como os docentes desta escola compreendem e vem inserindo a EA no cotidiano escolar., em uma escola estadual do município de Tangará da Serra/MT, Brasil. Para tanto, realizou-se entrevistas com os professores que fazem parte de um projeto interdisciplinar de EA na escola pesquisada. Verificou-se que o projeto da escola não vem conseguindo alcançar os objetivos propostos por: desconhecimento do mesmo, pelos professores; formação deficiente dos professores, não entendimento da EA como processo de ensino-aprendizagem, falta de recursos didáticos, planejamento inadequado das atividades. A partir dessa constatação, procurou-se debater a impossibilidade de tratar do tema fora do trabalho interdisciplinar, bem como, e principalmente, a importância de um estudo mais aprofundado de EA, vinculando teoria e prática, tanto na formação docente, como em projetos escolares, a fim de fugir do tradicional vínculo “EA e ecologia, lixo e horta”.Facultad de Humanidades y Ciencias de la Educació

Differentiation and CRISPR-Cas9-mediated genetic engineering of human intestinal organoids

Intestinal organoids are three-dimensional cultures that resemble key aspects of the epithelium of origin. Here, we describe how to differentiate human small intestinal organoids by combining growth media variations and genetic engineering. We detail the differentiation of human intestinal organoids in the presence and absence of BMP agonists to recapitulate a broader scope of functional cell states found in vivo. Using transient overexpression of the transcription factor Neurogenin-3, we describe the enhancement of differentiation toward rare enteroendocrine cells. For complete details on the use and execution of this protocol, please refer to Beumer et al. (2022)

Effects of Natural Between-Days Variation in Sleep on Elite Athletes’ Psychomotor Vigilance and Sport-Specific Measures of Performance

Performance capacity in athletes depends on the ability to recover from past exercise. While evidence suggests that athletic performance decreases following (partial) sleep deprivation and increases following sleep extension, it is unclear to which extent natural variation in sleep impacts performance. Sleep quantity and, for the first time, sleep stages were assessed among 98 elite athletes on three non-consecutive nights within a 7-day monitoring period, along with performance tests that were taken on standardized times each following morning. Performance assessment included psychomotor performance (10-minute psychomotor vigilance task) and sport-specific tests of fine (e.g., accuracy) and gross motor skills (e.g., endurance, power). Mixed-effects models were employed to assess the effect of sleep quantity (total sleep time (TST), sleep onset latency (SOL), wake after sleep onset, sleep efficiency) and sleep stage duration (light, deep, REM) on performance. Average TST was 7:30 ± 1:05 hours, with a mean variation of 57 minutes across days. Longer TSTs were associated with faster reaction times (p = 0.04). Analyses indicated small and inconsistent effects of sleep quantity (TST, SOL) and sleep staging (light sleep) on gross motor performance, and no effects on fine motor skill performance. Results indicate that natural variation in sleep quantity impacts psychomotor vigilance to a greater extent than athletic performance. Small or absent effects can be a consequence of the rather small variation in non-manipulated sleep. It is suggested that one night of compromised sleep may not be immediately problematic, but that more extreme sleep loss or accumulated sleep debt may have more severe consequences