Strategies to promote language inclusion at 17 CTSA hubs.

The prioritization of English language in clinical research is a barrier to translational science. We explored promising practices to advance the inclusion of people who speak languages other than English in research conducted within and supported by NIH Clinical Translational Science Award (CTSA) hubs. Key informant interviews were conducted with representatives (n = 24) from CTSA hubs (n = 17). Purposive sampling was used to identify CTSA hubs focused on language inclusion. Hubs electing to participate were interviewed via Zoom. Thematic analysis was performed to analyze interview transcripts. We report on strategies employed by hubs to advance linguistic inclusion and influence institutional change that were identified. Strategies ranged from translations, development of culturally relevant materials and consultations to policies and procedural changes and workforce initiatives. An existing framework was adapted to conceptualize hub strategies. Language justice is paramount to bringing more effective treatments to all people more quickly. Inclusion will require institutional transformation and CTSA hubs are well positioned to catalyze change.

Use of Topical Corticosteroids in the Treatment of Noninfectious Inflammatory Dermatoses of the Scalp: A Survey of Practicing Dermatologists and Dermatology Residents Using Delphi Methodology.

Background: Noninfectious inflammatory dermatoses of the scalp are common, and their symptomsin particular, those affecting appearance, can have a psychological effect that may be disproportionate to their clinical severity. Effective, cosmetically acceptable treatments are important to manage these conditions. Topical corticosteroids form the cornerstone of acute treatment for many of these conditions. We surveyed practicing dermatologists and dermatology residents to determine the current clinical practice in prescribing topical corticosteroids for these disorders in their various preparation formats. Methods: A Delphi method was used, consisting of 2 questionnaire rounds. The first round contained 34 questions and was completed by 612 dermatologists and dermatology residents via email. The first round of responses was analyzed, and points that had > 70% agreement were used to form a second questionnaire of 21 statements. This second round was completed by 346 participants, and their responses were used to generate a final report. Participants were practicing in both public and private practices. Results: Clobetasol propionate 0.05% topical solution was considered to be the most appropriate treatment for noninfectious inflammatory scalp dermatoses in general, with 75.1% agreement in the second round of questionnaire. The main advantages of clobetasol propionate over other topical corticosteroids were reported as potency, effectiveness, and broad action spectrum (94.8% agreement). The preferred pharmaceutical format was the solution of clobetasol propionate. Conclusion: Clobetasol propionate was the preferred topical treatment for the management of scalp dermatoses, usually as first-line treatment; solution was the preferred preparation.

Transcriptomic Profiling of Pleural Effusions: Differences in Malignant and Infectious Fluids.

Background and Objectives: Different cellular and molecular processes are involved in the production of malignant and infectious pleural effusions. However, the underlying mechanisms responsible for these differences or their consequences remain incompletely understood. The objective of this study was to identify differences in gene expression in pleural exudates of malignant and infectious aetiology and establish the possible different biological processes involved in both situations. Materials and Methods: RNA transcriptomic analysis was performed on 46 pleural fluid samples obtained during diagnostic thoracocenteses from 46 patients. There were 35 exudates (19 malignant and 16 infectious effusions) and 11 transudates that were used as a reference control group. Differential gene expression analysis for both exudative groups was identified. An enrichment score using the Human Kegg Orthology database was used for establishing the biological processes associated with malignant and infectious pleural effusions. Results: When comparing malignant exudates with infectious effusions, 27 differentially expressed genes with statistical significance were identified. Network analysis showed ten different biological processes for malignant and for infectious pleural effusions. In malignant fluids, processes related to protein synthesis and processing predominate. In infectious exudates, biological processes in connection with ATP production prevail. Conclusions: This study demonstrates differentially expressed genes in malignant and infectious pleural effusions, which could have important implications in the search for diagnostic or prognostic biomarkers. In addition, for the first time, biological processes involved in these two causes of pleural exudates have been described.

Size matters: Functional differences of small extracellular vesicle subpopulations in cardiac repair responses.

Cardiac progenitor cell (CPC)-derived small extracellular vesicles (sEVs) exhibit great potential to stimulate cardiac repair. However, the multifaceted nature of sEV heterogeneity presents a challenge in understanding the distinct mechanisms underlying their regenerative abilities. Here, a dual-step multimodal flowthrough and size-exclusion chromatography method was applied to isolate and separate CPC-derived sEV subpopulations to study the functional differences related to cardiac repair responses. Three distinct sEV subpopulations were identified with unique protein profiles. Functional cell assays for cardiac repair-related processes demonstrated that the middle-sized and smallest-sized sEV subpopulations exhibited the highest pro-angiogenic and anti-fibrotic activities. Proteasome activity was uniquely seen in the smallest-sized subpopulation. The largest-sized subpopulation showed no effect in any of the functional assays. This research uncovers the existence of sEV subpopulations, each characterized by a distinct composition and biological function. Enhancing our understanding of sEV heterogeneity will provide valuable insights into sEV mechanisms of action, ultimately accelerating the translation of sEV therapeutics.

Patient and Provider Experiences and Views on the Use of Telehealth in Genetics Clinics in Response to the COVID-19 Pandemic.

Introduction: The 2019 Coronavirus Disease (COVID-19) pandemic necessitated a mass transition in genetics clinics nationwide from in-person care to virtual care through telehealth. Before the COVID-19 pandemic, there was limited research on the use of telehealth in genetics specialties. Therefore, the COVID-19 pandemic presented a unique opportunity to study this emerging mode of care delivery in the setting of genetics clinics. This study described the scope of telehealth use in genetics clinics nationally and determined how COVID-19 influenced patients' decisions regarding their genetic care. Methods: Two anonymous surveys for patients and providers were developed. The patient survey was offered online to all genetics patients seen through telehealth at a Manhattan-based practice between March and December 2020. The provider survey was distributed through several listservs to genetics providers nationwide. Results: Patients (n = 242) and providers (n = 150) responded. Telehealth was used in all specialty genetics clinics for both initial and follow-up visits. Telehealth was both effective and satisfactory to patients for both visit types and across specialties; however, Asian and Hispanic/Latino patients had significantly lower mean satisfaction scores compared with White patients (p = 0.03 and 0.04, respectively). Patients appreciated telehealth for its convenience and to avoid COVID-19 exposure. Providers across specialties and provider types preferred telehealth for follow-up rather than initial visits. Several clinic initiatives related to telehealth were identified. Discussion: Telehealth was generally well received by both patients and providers, and is expected to become permanent option in genetics clinics. Further studies are needed to identify barriers to accessing telehealth.

Comprehensive Older Adult and Caregiver Help (COACH): A person-centered caregiver intervention prevents elder mistreatment.

BACKGROUND: Elder mistreatment (EM) harms individuals, families, communities, and society as a whole. Yet research on interventions is lagging, and no rigorous studies demonstrating effective prevention have been published. This pilot study examines whether a first-of-its-kind coaching intervention reduced the experience of EM among older adults with chronic health conditions, including dementia. METHODS: We used a double-blind, randomized controlled trial to test a strengths-based person-centered caregiver support intervention, developed from evidence-based approaches used in other types of family violence. Participants (n = 80), family caregivers of older adults who were members of Kaiser Permanente, completed surveys at baseline, post-test, and 3-month follow-up. The primary outcome was caregiver-reported EM; additional proximal outcomes were caregiver burden, quality-of-life, anxiety, and depression. Nonparametric tests (Mann-Whitney U, Fisher's Exact, Wilcoxon Signed Rank, and McNemar's) were used to make comparisons between treatment and control groups and across time points. RESULTS: The treatment group had no EM after intervention completion (assessed at 3-month follow-up), a significantly lower rate than the control group (treatment = 0%, control = 23.1%, p = 0.010). CONCLUSIONS: In this pilot study, we found that the COACH caregiver support intervention successfully reduced EM of persons living with chronic illness, including dementia. Next steps will include: (1) testing the intervention's mechanism in a fully powered RCT and (2) scaling the intervention for testing in a variety of care delivery systems.

Suramin, a drug for the treatment of trypanosomiasis, reduces the prothrombotic and metastatic phenotypes of colorectal cancer cells by inhibiting hepsin.

Recently, our group identified serine-protease hepsin from primary tumor as a biomarker of metastasis and thrombosis in patients with localized colorectal cancer. We described hepsin promotes invasion and thrombin generation of colorectal cancer cells in vitro and in vivo and identified venetoclax as a hepsin inhibitor that suppresses these effects. Now, we aspire to identify additional hepsin inhibitors, aiming to broaden the therapeutic choices for targeted intervention in colorectal cancer. METHODS: We developed a virtual screening based on molecular docking between the hepsin active site and 2000 compounds from DrugBank. The most promising drug was validated in a hepsin activity assay. Subsequently, we measured the hepsin inhibitor effect on colorectal cancer cells with basal or overexpression of hepsin via wound-healing, gelatin matrix invasion, and plasma thrombin generation assays. Finally, a zebrafish model determined whether hepsin inhibition reduced the invasion of colorectal cancer cells overexpressing hepsin. RESULTS: Suramin was the most potent hepsin inhibitor (docking score: -11.9691 Kcal/mol), with an IC50 of 0.66 µM. In Caco-2 cells with basal or overexpression of hepsin, suramin decreased migration and significantly reduced invasion and thrombin generation. Suramin did not reduce the thrombotic phenotype in the hepsin-negative colorectal cancer cells HCT-116 and DLD-1. Finally, suramin significantly reduced the in vivo invasion of Caco-2 cells overexpressing hepsin. CONCLUSION: Suramin is a novel hepsin inhibitor that reduces its protumorigenic and prothrombotic effects in colorectal cancer cells. This suggests the possibility of repurposing suramin and its derivatives to augment the repertoire of molecular targeted therapies against colorectal cancer.

Implementation of a dedicated cascade testing clinic for patients at risk for hereditary cancer syndromes.

Cascade testing, the site-specific genetic testing of relatives within families with an inherited condition, is underutilized. Long wait times for appointments in specialty genetics clinics are a known barrier to genetic testing access. In our cancer genetics, New Patient Clinic (NPC), the long wait time for an appointment (on average 5 months for routine referrals), was identified by both providers and patients as a barrier to uptake of cascade testing. Timely testing of at-risk relatives is essential to maximize the benefits of cascade testing and reduce cancer morbidity and mortality. Our objective was to improve access via implementation of a different clinical model that designated appointments for patients seeking cascade testing. A secondary goal was to improve use of genetic counselor time. We implemented a dedicated Cascade Testing Clinic (CTC) with an expedited triaging and unique scheduling model to decrease patient wait time to appointment and optimize clinician time. We report on the process and outcomes here. Between October 2016 and February 2020, the average wait time between referral date and first scheduled appointment date was 46 days for the CTC compared to 144 days for the NPC (p < 0.0001). No-show/cancelation/rescheduling rate was 11.7% in the CTC compared to 29.7% in the NPC (p < 0.0001). Genetic counselors saw approximately twice as many patients per half-day clinic in the CTC compared to the NPC (p < 0.00001). Modifications to clinic staffing and appointment times were made based on provider feedback. Implementation of a dedicated clinic specifically for patients seeking cascade testing significantly shortened wait times for this population, reduced patient drop-off, and improved clinician efficiency. The relatively straightforward indications and generally uncomplicated medical histories made this an ideal population for expedited appointments.

Cardiac progenitor cell-derived extracellular vesicles promote angiogenesis through both associated- and co-isolated proteins.

Extracellular vesicles (EVs) are cell-derived lipid bilayer-enclosed particles that play a role in intercellular communication. Cardiac progenitor cell (CPC)-derived EVs have been shown to protect the myocardium against ischemia-reperfusion injury via pro-angiogenic effects. However, the mechanisms underlying CPC-EV-induced angiogenesis remain elusive. Here, we discovered that the ability of CPC-EVs to induce in vitro angiogenesis and to stimulate pro-survival pathways was lost upon EV donor cell exposure to calcium ionophore. Proteomic comparison of active and non-active EV preparations together with phosphoproteomic analysis of activated endothelial cells identified the contribution of candidate protein PAPP-A and the IGF-R signaling pathway in EV-mediated cell activation, which was further validated using in vitro angiogenesis assays. Upon further purification using iodixanol gradient ultracentrifugation, EVs partly lost their activity, suggesting a co-stimulatory role of co-isolated proteins in recipient cell activation. Our increased understanding of the mechanisms of CPC-EV-mediated cell activation will pave the way to more efficient EV-based therapeutics.

Spanish validation of short-form version of Literacy of Suicide Scale (LOSS) and Stigma of Suicide Scale (SOSS).

INTRODUCTION: The evidence shows that a greater understanding of mental health and the myths about suicide is related to a reduction in these types of problems. OBJECTIVE: Validate the Literacy of Suicide Scale-Short Form (LOSS-SF) and the Stigma of Suicide Scale-Short Form (SOSS-SF) for Spain. MATERIALS AND METHODS: Both scales were translated to Spanish via backward translation. The sample was comprised of a total of 466 participants, of which 169 (36.2%) were men and 297 (63.6%) were women through nonrandom circumstantial sampling. The questionnaires were administered online. To test the factorial structure and evaluate reliability, both an EFA and an AFC were conducted. In addition, the reliability of the questionnaires was analyzed using the Omega coefficient and Cronbach's alpha. Finally, a linear regression analysis was carried out with the aim of testing the predictability of the scales. RESULTS AND DISCUSSION: The results obtained reveal acceptable fit indices and a factorial structure similar to that of the validation conducted for both instruments in other countries. The validity of these instruments for use in Spain is discussed.

Venetoclax is a potent hepsin inhibitor that reduces the metastatic and prothrombotic phenotypes of hepsin-expressing colorectal cancer cells.

Introduction: Hepsin is a type II transmembrane serine protease and its expression has been linked to greater tumorigenicity and worse prognosis in different tumors. Recently, our group demonstrated that high hepsin levels from primary tumor were associated with a higher risk of metastasis and thrombosis in localized colorectal cancer patients. This study aims to explore the molecular role of hepsin in colorectal cancer. Methods: Hepsin levels in plasma from resected and metastatic colorectal cancer patients were analyzed by ELISA. The effect of hepsin levels on cell migration, invasion, and proliferation, as well as on the activation of crucial cancer signaling pathways, was performed in vitro using colorectal cancer cells. A thrombin generation assay determined the procoagulant function of hepsin from these cells. A virtual screening of a database containing more than 2000 FDA-approved compounds was performed to screen hepsin inhibitors, and selected compounds were tested in vitro for their ability to suppress hepsin effects in colorectal cancer cells. Xenotransplantation assays were done in zebrafish larvae to study the impact of venetoclax on invasion promoted by hepsin. Results: Our results showed higher plasma hepsin levels in metastatic patients, among which, hepsin was higher in those suffering thrombosis. Hepsin overexpression increased colorectal cancer cell invasion, Erk1/2 and STAT3 phosphorylation, and thrombin generation in plasma. In addition, we identified venetoclax as a potent hepsin inhibitor that reduced the metastatic and prothrombotic phenotypes of hepsin-expressing colorectal cancer cells. Interestingly, pretreatment with Venetoclax of cells overexpressing hepsin reduced their invasiveness in vivo. Discussion: Our results demonstrate that hepsin overexpression correlates with a more aggressive and prothrombotic tumor phenotype. Likewise, they demonstrate the antitumor role of venetoclax as a hepsin inhibitor, laying the groundwork for molecular-targeted therapy for colorectal cancer.

European dietitians as key agents of the green transition: An exploratory study of their knowledge, attitudes, practices, and training.

Introduction: How food systems are currently provisioning food to the population is a matter of debate worldwide. Food systems, driven by widespread and increasing adherence to a westernized dietary pattern, are failing to meet people's basic needs and are draining natural resources. There is a push to make food systems more healthy, fair, and sustainable. To this end, action from all players is needed to meet the international agenda. In this regard, dietitians play a crucial role, as they can provide advice and promote actions that foster the adoption of more sustainable dietary patterns (SDP) as well as the promotion of sustainable food systems. As an emerging requirement in their training, it is crucial to know what dietitians know about SDP as well as their attitudes and current practices in this field in order to strengthen their competences and be key agents for the green transition. For this reason, the aim of the present study is to explore the knowledge, attitudes, practices, and training (KAPT) of European dietitians on SDP by administering an online survey. Methods: Cross-sectional survey administered between April-August 2021 to dietitians based in the European countries with National Dietetic Associations or Education Associate Members affiliated to the European Federation of Associations of Dietitians (EFAD). Results were analyzed based on European region of professional practice (Northern/Southern/Western/South-East Europe), area of expertise and years of experience. Results: Responses from 2211 dietitians from 25 countries were received, although the analysis was based on those that responded at least 90% of the survey (n=208). European dietitians are lacking training on SDP but are willing to learn more about it. Most dietitians perceive themselves as able to define an SDP, although aspects concerning social and economic sustainability were underestimated. Dietitians concur that barriers exist to the promotion of SDP, such as the lack of updated national food-based dietary guidelines and the absence of support from peers and managers. The country of professional activity seemed to be key to influencing dietitians' KAPT. Discussion: These results emphasize the need to strengthen European dietitians' training in SDP and increase public/private commitment to consider dietitians as key professionals for the transition towards SDP.

Resemblances in the early development of two sea urchins: Toxopneustes roseus (Euechinoidea: Echinacea) and Rhyncholampas pacificus (Euechinoidea: Irregularia) from different habitats in the southern Mexican Pacific.

Sea urchins play a key role in the marine environment, contributing to maintain a balance in benthic ecosystems. Toxopneustes roseus acts as a regulator of rhodolith beds and is a key species as a bioturbation promoter, while Rhyncholampas pacificus moderates the detritus content of sediment through various mechanisms and contributes to accelerating the circulation of organic matter. However, nothing is known about their early development, so the objective of this research is to characterize the embryonic and larval development of specimens of the two species from the southern Mexican Pacific and identify the causes that produce their differences. The embryonic development of T. roseus lasted approximately 20 â€‹h; the echinopluteus larva appeared at 23 â€‹h and culminated in around 12 days with an eight-armed larva. Metamorphosis was reached at 18 days. The embryonic development of R. pacificus lasted about 15 â€‹h; the larva emerged at 20 â€‹h and culminated in about two days with an eight-armed larva. The metamorphosis was completed in 9 days. The reproductive output of both species determines their development time and the structure of their larvae; therefore, the energy of R. pacificus is invested in reaching metamorphosis earlier to ensure that its larvae, which are not very abundant, settle and recruit to the population. Regarding T. roseus, the longest permanence in the plankton is efficiently maintained by its numerous larvae through the presence of mobile arms and the shift of the swimming function to the epauletes. This is the first work that characterizes the early development of a species of the genus Toxopneustes and of the only living species of the genus Ryncholampas. The information generated in this work is essential to gaining knowledge about these groups of echinoids, especially the effect of the environment on their early development.

Eficacia del bórax en el tratamiento de la estomatitis aftosa

Fundamento: la estomatitis aftosa es una enfermedad crónica caracterizada por la ulceración de la mucosa bucal no queratinizada, que se presenta de forma aguda y dolorosa. Objetivo: evaluar la eficacia del bórax en el tratamiento de la estomatitis aftosa. Métodos: se realizó un estudio analítico, longitudinal prospectivo, en el Departamento de Estomatología del Policlínico Norte, Ángel del Castillo Agramonte, del municipio de Florida, en el período comprendido de diciembre del 2019 hasta abril del 2021. El universo estuvo constituido por 139 pacientes, y la muestra quedó conformada por 70 pacientes seleccionados por un método aleatorio simple. La misma quedó dividida en dos grupos: uno de estudio y otro de control a los que se le aplicó un tratamiento homeopático con bórax y un tratamiento convencional, respectivamente. Resultados: el rango de edad más afectado fue el de 21- 30 años, y el sexo femenino fue el más representado; los labios constituyeron el sitio de mayor afectación y prevaleció la estomatitis aftosa en su forma menor. En cada visita de control se observó una mejor evolución del dolor, el ardor y la cicatrización de las lesiones con el tratamiento homeopático, que con el convencional; se observó una efectividad de un 100 % en los pacientes tratados con bórax y la mayoría de los pacientes se mostró satisfecha con el tratamiento homeopático recibido. Conclusiones: el bórax resulta eficaz para el tratamiento de la estomatitis aftosa.

Background: aphthous stomatitis is a chronic disease characterized by the non-keratinized oral mucosa ulceration, which presents acutely and painfully. Objective: to evaluate the efficacy of borax in the aphthous stomatitis treatment. Methods: an analytical, longitudinal prospective study was carried out in the North Polyclinic Stomatology Department, Ángel del Castillo Agramonte, in the Florida municipality, from December 2019 to April 2021. 139 patients were studied and the sample was made up of 70 patients selected by a simple random method. It was divided into two groups: a study group and a control group to which a homeopathic treatment with borax and a conventional treatment were applied, respectively. Results: the most affected age range was 21-30 years old, and the female sex was the most represented; the lips were the most affected site and aphthous stomatitis prevailed in its minor form. At each control visit, a better evolution of pain, burning, and healing of the lesions was observed with the homeopathic treatment than with the conventional one; an effectiveness of 100% was observed in the patients treated with borax and the majority of the patients were satisfied with the homeopathic treatment received. Conclusions: borax is effective for the treatment of aphthous stomatitis.

Use of a Community Engagement and Research Core model to enhance primary care provider recruitment: A case example.

Persistent barriers exist to engage rural providers in research and training. Provider shortages exacerbate these challenges, leading to a scarcity of time and limiting motivation to participate in research. We present application of an innovative engagement model to increase rural primary care provider participation in research. Using our Community Engagement and Research Core, we demonstrate that fundamental principles of training and expertise, attention to efficiency and multitasking, and commitment to community are important for addressing provider recruitment barriers. We encourage other Clinical and Translational Science Centers to provide similar services to their local investigators to enhance provider engagement in research.

Conceptualizing Person-Centered Care in Elder Mistreatment Intervention: Use of a Well-Being Framework.

BACKGROUND AND OBJECTIVES: Person-centered care (PCC) applied to elder mistreatment interventions is an approach to include victim priorities. Although PCC may improve outcomes by supporting choice, victim preferences are often difficult to support, especially in high-risk situations. We studied the adaptation of PCC structures and process to a pilot intervention, aimed at including client preferences in a multidisciplinary team's plans to address complex elder mistreatment. RESEARCH DESIGN AND METHODS: Case study analysis was used to examine the process of integrating client priorities into a risk-reduction plan. A well-being framework was used to understand the relationship between safety and preferences. Purposive sampling identified a case study of a high-risk victim with history of refusing help who agreed to work with the Service Advocate, a member of a multidisciplinary team. RESULTS: PCC required a relationship of trust, honed over several weeks by prioritizing the clients' perspective. Client preferences included remaining at home, continuing the relationship with the abuser, and maintaining a sense of mastery. Individualized definitions of "safety" were unrelated to elder mistreatment risk. Assistance included working with the suspected perpetrator, which is not offered by most elder mistreatment interventions, and resulted in some risk reduction. Reasons for refusing help were a desire for control and fear of loss of well-being assets. DISCUSSION AND IMPLICATIONS: Individualized definitions of well-being should be considered in measuring intervention success. Future research could determine guidelines on what levels of elder mistreatment risk are acceptable, and how to monitor clients for safety while supporting autonomy.

Trioecy is maintained as a time-stable mating system in the pink sea urchin Toxopneustes roseus from the Mexican Pacific.

Trioecy is a sexual system that consists of the co-occurrence of females, males and hermaphrodites in a population and is common in plants; however, in animals it is uncommon and poorly understood. In echinoderms, trioecy had never been recorded until now. Frequencies of females, males, and hermaphrodites were evaluated and gametogenic development was histologically characterized in a population of Toxopneustes roseus inhabiting the Mexican Pacific. Trioecy in this population is functional and temporally stable, since the three sexes coexisted in each sampling month. The hermaphrodites presented similar gametogenic development as the females and males and participated during the spawning season, contributing to the population's reproductive process. Trioecy is considered an evolutionarily transitory state, and it is extremely difficult to explain its presence in a species. We hypothesize that continuous ocean warming represents a threat to the survival of this population of T. roseus, since its early developmental stages, which represent a population bottleneck, are more vulnerable to high temperatures than other sea urchins inhabiting the area, while its population density is significantly lower. These conditions generate a strongly stressed environment, which is the determining factor that maintains the stability of trioecy in the species in which it has been studied.

Sleep quality among inpatients of Spanish public hospitals.

Sleep is a complex process and is needed both in health and illness. Deprivation of sleep is known to have multiple negative physiological effects on people's bodies and minds. Despite the awareness of these harmful effects, previous studies have shown that sleep is poor among hospitalised patients. We utilized an observational design with 343 patients recruited from medical and surgical units in 12 hospitals located in nine Spanish regions. Sociodemographic and clinical characteristics of patients were collected. Sleep quality at admission and during hospitalisation was measured by the Pittsburgh Sleep Quality Index. Sleep quantity was self-reported by patients in hours and minutes. Mean PSQI score before and during hospitalisation were respectively 8.62 ± 4.49 and 11.31 ± 4.04. Also, inpatients slept about an hour less during their hospital stay. Lower educational level, sedative medication intake, and multi-morbidity was shown to be associated with poorer sleep quality during hospitalisation. A higher level of habitual physical activity has shown to correlate positively with sleep quality in hospital. Our study showed poor sleep quality and quantity of inpatients and a drastic deterioration of sleep in hospital versus at home. These results may be helpful in drawing attention to patients' sleep in hospitals and encouraging interventions to improve sleep.

Mapping prohormone processing by proteases in human enteroendocrine cells using genetically engineered organoid models.

Enteroendocrine cells (EECs) secrete hormones in response to ingested nutrients to control physiological processes such as appetite and insulin release. EEC hormones are synthesized as large proproteins that undergo proteolytic processing to generate bioactive peptides. Mutations in EEC-enriched proteases are associated with endocrinopathies. Due to the relative rarity of EECs and a paucity of in vitro models, intestinal prohormone processing remains challenging to assess. Here, human gut organoids in which EECs can efficiently be induced are subjected to CRISPR-Cas9-mediated modification of EEC-expressed endopeptidase and exopeptidase genes. We employ mass spectrometry-based analyses to monitor peptide processing and identify glucagon production in intestinal EECs, stimulated upon bone morphogenic protein (BMP) signaling. We map the substrates and products of major EECs endo- and exopeptidases. Our studies provide a comprehensive description of peptide hormones produced by human EECs and define the roles of specific proteases in their generation.