Biomimetic and soft lab-on-a-chip platform based on enzymatic-crosslinked silk fibroin hydrogel for 3D cell co-culture.

Integrating biological material within soft microfluidic systems made of hydrogels offers countless possibilities in biomedical research to overcome the intrinsic limitations of traditional microfluidics based on solid, non-biodegradable, and non-biocompatible materials. Hydrogel-based microfluidic technologies have the potential to transformin vitrocell/tissue culture and modeling. However, most hydrogel-based microfluidic platforms are associated with device deformation, poor structural definition, reduced stability/reproducibility due to swelling, and a limited range in rigidity, which threatens their applicability. Herein, we describe a new methodological approach for developing a soft cell-laden microfluidic device based on enzymatically-crosslinked silk fibroin (SF) hydrogels. Its unique mechano-chemical properties and high structural fidelity, make this platform especially suited forin vitrodisease modelling, as demonstrated by reproducing the native dynamic 3D microenvironment of colorectal cancer and its response to chemotherapeutics in a simplistic way. Results show that from all the tested concentrations, 14 wt% enzymatically-crosslinked SF microfluidic platform has outstanding structural stability and the ability to perfuse fluid while displayingin vivo-like biological responses. Overall, this work shows a novel technique to obtain an enzymatically-crosslinked SF microfluidic platform that can be employed for developing soft lab-on-a-chipin vitromodels.

Human Tendon-on-Chip: Unveiling the Effect of Core Compartment-T Cell Spatiotemporal Crosstalk at the Onset of Tendon Inflammation.

The lack of representative in vitro models recapitulating human tendon (patho)physiology is among the major factors hindering consistent progress in the knowledge-based development of adequate therapies for tendinopathy.Here, an organotypic 3D tendon-on-chip model is designed that allows studying the spatiotemporal dynamics of its cellular and molecular mechanisms.Combining the synergistic effects of a bioactive hydrogel matrix with the biophysical cues of magnetic microfibers directly aligned on the microfluidic chip, it is possible to recreate the anisotropic architecture, cell patterns, and phenotype of tendon intrinsic (core) compartment. When incorporated with vascular-like vessels emulating the interface between its intrinsic-extrinsic compartments, crosstalk with endothelial cells are found to drive stromal tenocytes toward a reparative profile. This platform is further used to study adaptive immune cell responses at the onset of tissue inflammation, focusing on interactions between tendon compartment tenocytes and circulating T cells.The proinflammatory signature resulting from this intra/inter-cellular communication induces the recruitment of T cells into the inflamed core compartment and confirms the involvement of this cellular crosstalk in positive feedback loops leading to the amplification of tendon inflammation.Overall, the developed 3D tendon-on-chip provides a powerful new tool enabling mechanistic studies on the pathogenesis of tendinopathy as well as for assessing new therapies.

Chemsex Session Typologies and Associated Sociodemographic Factors in Sexual Minority Men: Latent Class Analysis From a Cultural Perspective Using a Cross-Sectional Survey.

Background: Chemsex prevalence is still not well known, and both the lack of homogeneity and cultural component of chemsex practices are usually overlooked. Objective: This study aims to estimate the proportion of sexual minority men (SMM) engaging in chemsex sessions, while understanding the cultural dimension of chemsex, and to analyze distinct session typologies with potential risk differences and the sociodemographic factors associated with engaging in them. Methods: A total of 5711 SMM residing throughout Spain participated in an anonymous web-based survey that assessed chemsex session engagement and characteristics, drug use, and sociodemographic variables. We measured the association of sociodemographic factors with engaging in chemsex sessions by calculating adjusted prevalence ratios, using multivariate Poisson regression analysis. Chemsex typologies were analyzed using latent class analysis, and sociodemographic factors were associated with the different risk classes. Results: Our results determined that 21.1% (1205/5711; 95% CI 20.0%-22.1%) of SMM engaged in chemsex sessions during their lifetime. Participating in sessions was significantly associated with being a migrant, not having a comfortable financial situation, openly living their sexuality, residing in bigger municipalities, older age, using steroids, and living with HIV (adjusted prevalence ratio: range 1.17-2.01; all P values <.05). Three typologies of sessions with different risks were identified with latent class analysis, with 23.2% of SMM engaging in sessions taking part in higher-risk ones, which was associated with younger age, using steroids, living in bigger municipalities, openly living their sexuality, and living with HIV, compared to SMM engaging in lower-risk sessions (odds ratio: range 2.75-4.99). Conclusions: Chemsex is relatively common among SMM in Spain, but it is important to differentiate typologies of sessions with varying risks, and the proportion of SMM engaging in high-risk sessions is low. Chemsex is highly associated with sociodemographic factors. Chemsex should be prioritized in public health programs, which should consider the different forms of sessions with their varying risks and prevalence, while also considering the cultural dimension inherent to chemsex.

Evaluation of Novel Dendrimer-Gold Complex Nanoparticles for Theranostic Application in Oncology.

AIM: Despite some successful examples of therapeutic nanoparticles reaching clinical stages, there is still a significant need for novel formulations in order to improve the selectivity and efficacy of cancer treatment. METHODS: The authors developed two novel dendrimer-gold (Au) complex-based nanoparticles using two different synthesis routes: complexation method (formulation A) and precipitation method (formulation B). Using a biomimetic cancer-on-a-chip model, the authors evaluated the possible cytotoxicity and internalization by colorectal cancer cells of dendrimer-Au complex-based nanoparticles. RESULTS: The results showed promising capabilities of these nanoparticles for selectively targeting cancer cells and delivering drugs, particularly for the formulation A nanoparticles. CONCLUSION: This work highlights the potential of dendrimer-Au complex-based nanoparticles as a new strategy to improve the targeting of anticancer drugs.

A brain MRI dataset and baseline evaluations for tumor recurrence prediction after Gamma Knife radiotherapy.

Prediction and identification of tumor recurrence are critical for brain cancer treatment design and planning. Stereotactic radiation therapy delivered with Gamma Knife has been developed as one of the common treatment approaches combined with others by delivering radiation that targets accurately on the tumor while not affecting nearby healthy tissues. In this paper, we release a fully publicly available brain cancer MRI dataset and the companion Gamma Knife treatment planning and follow-up data for the purpose of tumor recurrence prediction. The dataset contains original patient MRI images, radiation therapy data, and clinical information. Lesion annotations are provided, and inclusive preprocessing steps have been specified to simplify the usage of this dataset. A baseline framework based on a convolutional neural network is proposed companionably with basic evaluations. The release of this dataset will contribute to the future development of automated brain tumor recurrence prediction algorithms and promote the clinical implementations associated with the computer vision field. The dataset is made publicly available on The Cancer Imaging Archive (TCIA) ( https://doi.org/10.7937/xb6d-py67 ).

Frequency and phenotypic spectrum of spinocerebellar ataxia 27B and other genetic ataxias in a Spanish cohort of late-onset cerebellar ataxia.

BACKGROUND AND PURPOSE: Dominantly inherited GAA repeat expansions in the fibroblast growth factor 14 (FGF14) gene have recently been shown to cause spinocerebellar ataxia 27B (SCA27B). We aimed to study the frequency and phenotype of SCA27B in a cohort of patients with unsolved late-onset cerebellar ataxia (LOCA). We also assessed the frequency of SCA27B relative to other genetically defined LOCAs. METHODS: We recruited a consecutive series of 107 patients with LOCA, of whom 64 remained genetically undiagnosed. We screened these 64 patients for the FGF14 GAA repeat expansion. We next analysed the frequency of SCA27B relative to other genetically defined forms of LOCA in the cohort of 107 patients. RESULTS: Eighteen of 64 patients (28%) carried an FGF14 (GAA)≥250 expansion. The median (range) age at onset was 62.5 (39-72) years. The most common clinical features included gait ataxia (100%) and mild cerebellar dysarthria (67%). In addition, episodic symptoms and downbeat nystagmus were present in 39% (7/18) and 37% (6/16) of patients, respectively. SCA27B was the most common cause of LOCA in our cohort (17%, 18/107). Among patients with genetically defined LOCA, SCA27B was the main cause of pure ataxia, RFC1-related disease of ataxia with neuropathy, and SPG7 of ataxia with spasticity. CONCLUSION: We showed that SCA27B is the most common cause of LOCA in our cohort. Our results support the use of FGF14 GAA repeat expansion screening as a first-tier genetic test in patients with LOCA.

Trapping metastatic cancer cells with mechanical ratchet arrays.

Current treatments for cancer, such as chemotherapy, radiotherapy, immunotherapy, and surgery, have positive results but are generally ineffective against metastatic tumors. Treatment effectiveness can be improved by employing bioengineered cancer traps, typically utilizing chemoattractant-loaded materials, to attract infiltrating cancer cells preventing their uncontrolled spread and potentially enabling eradication. However, the encapsulated chemical compounds can have adverse effects on other cells causing unwanted responses, and the generated gradients can evolve unpredictably. Here, we report the development of a cancer trap based on mechanical ratchet structures to capture metastatic cells. The traps use an array of asymmetric local features to mechanically attract cancer cells and direct their migration for prolonged periods. The trapping efficiency was found to be greater than isotropic or inverse anisotropic ratchet structures on either disseminating cancer cells and tumor spheroids. Importantly, the traps exhibited a reduced effectiveness when targeting non-metastatic and non-tumorigenic cells, underscoring their particular suitability for capturing highly invasive cancer cells. Overall, this original approach may have therapeutic implications for fighting cancer, and may also be used to control cell motility for other biological processes. STATEMENT OF SIGNIFICANCE: Current cancer treatments have limitations in treating metastatic tumors, where cancer cells can invade distant organs. Biomaterials loaded with chemoattractants can be implanted to attract and capture metastatic cells preventing uncontrolled spread. However, encapsulated chemical compounds can have adverse effects on other cells, and gradients can evolve unpredictably. This paper presents an original concept of "cancer traps" based on using mechanical ratchet-based structures to capture metastatic cancer cells, with greater trapping efficiency and stability than previously studied methods. This innovative approach has significant potential clinical implications for fighting cancer, particularly in treating metastatic tumors. Additionally, it could be applied to control cell motility for other biological processes, opening new possibilities for biomedicine and tissue engineering.

Microlearning through TikTok in Higher Education. An evaluation of uses and potentials.

While social media is evolving rapidly, understanding its underlying and persistent features with the potential to support high-quality learning would provide opportunities to enhance competence acquisition and collaborative work in higher education. Moreover, the adoption of tools that students already use in their everyday lives facilitates the integration of new forms of learning. In this context, we have developed an initiative to disseminate content through TikTok in three modules of the Bachelor's Degree in Nursing course, with the aim of promoting quality learning through these microlearning environments. To this end, we have implemented these learning environments and evaluated the users' perceptions, as well as their level of acceptance of the technology according to the Technology Acceptance Model. Overall, our results show high levels of satisfaction with regard to engagement and the content generated, as well as in terms of the acceptance of the technology. Our results do not show gender-specific variations, but we did detect slight variations depending on the subject in which the microlearning tool was deployed. Although for the most part these variations do not change the participants' assessment of their experience, it will be necessary in the future to determine the underlying reasons for these variations. In addition, our results suggest that it is possible to design a content creation system to promote quality learning through microlearning that can be transferred to other subjects, at least in the Bachelor's Degree in Nursing. Supplementary Information: The online version contains supplementary material available at 10.1007/s10639-023-11904-4.

Acute Effects of a Session with The EXOPULSE Mollii Suit in a Fibromyalgia Patient: A Case Report.

Fibromyalgia is a chronic disorder characterized by widespread musculoskeletal pain and associated fatigue, sleep disturbances, and other cognitive and somatic symptoms. A multidisciplinary approach including pharmacological therapies along with behavioral therapy, exercise, patient education, and pain management is a possible solution for the treatment of this disease. The EXOPULSE Mollii® method (EXONEURAL NETWORK AB, Danderyd, Sweden) is an innovative approach for non-invasive and self-administered electrical stimulation with multiple electrodes incorporated in a full-body suit, with already proven benefits for other diseases. Therefore, the present case report study aims to evaluate the effects that a 60 min session with the EXOPULSE Mollii suit has on a female fibromyalgia patient. After the intervention, we can conclude that a 60 min session with the EXOPULSE Mollii suit has beneficial effects on pain perception, muscle oxygenation, parasympathetic modulation, and function in a female fibromyalgia patient.

Assessing cell migration in hydrogels: An overview of relevant materials and methods.

Cell migration is essential in numerous living processes, including embryonic development, wound healing, immune responses, and cancer metastasis. From individual cells to collectively migrating epithelial sheets, the locomotion of cells is tightly regulated by multiple structural, chemical, and biological factors. However, the high complexity of this process limits the understanding of the influence of each factor. Recent advances in materials science, tissue engineering, and microtechnology have expanded the toolbox and allowed the development of biomimetic in vitro assays to investigate the mechanisms of cell migration. Particularly, three-dimensional (3D) hydrogels have demonstrated a superior ability to mimic the extracellular environment. They are therefore well suited to studying cell migration in a physiologically relevant and more straightforward manner than in vivo approaches. A myriad of synthetic and naturally derived hydrogels with heterogeneous characteristics and functional properties have been reported. The extensive portfolio of available hydrogels with different mechanical and biological properties can trigger distinct biological responses in cells affecting their locomotion dynamics in 3D. Herein, we describe the most relevant hydrogels and their associated physico-chemical characteristics typically employed to study cell migration, including established cell migration assays and tracking methods. We aim to give the reader insight into existing literature and practical details necessary for performing cell migration studies in 3D environments.

Trombocitopenia severa inducida por un oclusor para DAP: reporte de caso en tecnovigilancia

Introducción: El ductus arterioso persistente (DAP) es una cardiopatía congénita de especial interés. La oclusión intervencionista es el tratamiento de elección, no obstante, el dispositivo médico "oclusor para DAP", usado en este procedimiento, puede dar lugar a la aparición de eventos adversos de rara frecuencia como hemorragia, trombocitopenia, entre otros. Reporte de caso: Se presenta un caso de una paciente pediátrica con trombocitopenia severa posterior a la intervención. Durante su hospitalización, la paciente mantuvo niveles bajos de plaquetas hasta que logra su recuperación y sale de alta sin una nueva manifestación hematológica. El caso fue reportado como sospecha de incidente adverso asociada al oclusor para DAP. Conclusión: Al realizarse el análisis causa-raíz, se concluye que el tamaño del oclusor para DAP podría ser la principal causa de la trombocitopenia. El presente caso es una muestra que los dispositivos médicos pueden causar eventos adversos severos, por lo que, es necesaria la implementación de tecnovigilancia, principalmente a los dispositivos médicos de alto riesgo.

Introduction: Patent ductus arteriosus (PDA) is a congenital heart condition of special interest. Interventional occlusion is the treatment of choice; however, a PDA occlude, used in this procedure, is a medical device that rarely could lead to adverse events such as hemorrhage, thrombocytopenia, etc. Case report: We present a case of a pediatric patient with severe thrombocytopenia after surgery. During her hospitalization, platelet levels remained lower and, finally, she was fully recovered without any hematological manifestation. The case was reported as a suspected adverse incident related to PDA occlude. Conclusion: After performing a cause-root analysis, we concluded that the size of the PDA occlude may be the main cause of thrombocytopenia. This case demonstrates that medical devices could lead to adverse events. Thus, it is important for clinicians to implement medical device surveillance, mainly for high-risk medical devices.

Shining a Light on Cancer-Photonics in Microfluidic Tumor Modeling and Biosensing.

Microfluidic platforms represent a powerful approach to miniaturizing important characteristics of cancers, improving in vitro testing by increasing physiological relevance. Different tools can manipulate cells and materials at the microscale, but few offer the efficiency and versatility of light and optical technologies. Moreover, light-driven technologies englobe a broad toolbox for quantifying critical biological phenomena. Herein, the role of photonics in microfluidic 3D cancer modeling and biosensing from three major perspectives is reviewed. First, optical-driven technologies are looked upon, as these allow biomaterials and living cells to be manipulated with microsized precision and present opportunities to advance 3D microfluidic models by engineering cancer microenvironments' hallmarks, such as their architecture, cellular complexity, and vascularization. Second, the growing field of optofluidics is discussed, exploring how optical tools can directly interface microfluidic chips, enabling the extraction of relevant biological data, from single fluorescent signals to the complete 3D imaging of diseased cells within microchannels. Third, advances in optical cancer biosensing are reviewed, focusing on how light-matter interactions can detect biomarkers, rare circulating tumor cells, and cell-derived structures such as exosomes. Photonic technologies' current challenges and caveats in microfluidic 3D cancer models are overviewed, outlining future research avenues that may catapult the field.

Asociación entre tiroiditis linfocítica crónica y carcinoma papilar de tiroides: Revisión sistemática y metaanálisis de estudios en especímenes quirúrgicos / Association between chronic lymphocityc thyroiditis and papillary thyroid carcinoma: Systematic review and meta-analysis of studieson surgical specimens

Introducción. Existen resultados inconsistentes con relación al planteamiento de la hipótesis que sugiere una mayor probabilidad de documentar un carcinoma papilar de tiroides en especímenes quirúrgicos con cambios compatibles con tiroiditis linfocítica crónica. En los metaanálisis existentes se han incluido estudios no comparables metodológicamente y no se proponen claras fuentes de sesgo, justificación para la realización del presente metaanálisis. Métodos. Se realizó una búsqueda bibliográfica en Pubmed y Embase. Fueron obtenidos estudios retrospectivos donde se comparaba la prevalencia de carcinoma papilar de tiroides en especímenes con y sin cambios por tiroiditis linfocítica crónica. La evidencia recolectada fue sintetizada estadísticamente. Resultados. Un total de 22 artículos fueron incluidos. La población estuvo conformada por 63.548 especímenes. El OR combinado fue 1,81 (IC95%: 1,51-2,21). Hubo heterogeneidad entre la distribución de las razones de oportunidad entre los estudios (I2= 91 %; p>0,00001). La forma del gráfico en embudo de los estudios incluidos en el análisis parece estar simétrica, lo que indica la ausencia del sesgo atribuible a los estudios pequeños. Conclusiones. La literatura actual sugiere que existe un mayor riesgo de documentar un carcinoma papilar de tiroides en especímenes quirúrgicos en los que se observan cambios compatibles con tiroiditis linfocítica crónica; sin embargo, existen fuentes de sesgo que no será posible controlar en estudios retrospectivos, por lo que recomendamos estudiar la hipótesis que sugiere una mayor probabilidad de diagnosticar un carcinoma papilar de tiroides en especímenes con cambios compatibles con tiroiditis linfocítica crónica mediante metodologías prospectivas

Introduction. Inconsistent results exist in the literature regarding the hypothesis statement suggesting an increased likelihood of documenting papillary thyroid carcinoma (PTC) in surgical specimens with changes compatible with chronic lymphocytic thyroiditis. Existing meta-analyses have included studies that are not methodologically comparable and do not propose clear sources of bias, thus, this is justification for the present meta-analysis. Methods. A literature search in Pubmed and Embase was performed from January 1, 1950 to December 31, 2020. Retrospective studies comparing the prevalence of papillary thyroid carcinoma in specimens with and without chronic lymphocytic thyroiditis changes were obtained. The collected evidence was statistically analyzed. Results. A total of 22 articles were included. The study population consisted of 63,548 surgical specimens. The pooled OR, based on the studies, was 1.81 (95% CI: 1.51-2.21). There was heterogeneity between the distribution of prevalence ratios and opportunity ratios across studies (I²= 91%; p>0.00001). The funnel plot shape of the studies included in the analysis appears to be symmetrical, indicating the absence of bias attributable to small studies. Conclusions. The current literature suggests that there is an increased risk of documenting papillary thyroid carcinoma in surgical specimens in which chronic lymphocytic thyroiditis-compatible changes are observed; however, there are sources of bias that will not be possible to control for in retrospective studies, so we recommend studying the hypothesis suggesting an increased likelihood of diagnosing PTC in specimens with chronic lymphocytic thyroiditis-compatible changes using prospective methodologies

Boosting the Clinical Translation of Organ-on-a-Chip Technology.

Organ-on-a-chip devices have become a viable option for investigating critical physiological events and responses; this technology has matured substantially, and many systems have been reported for disease modeling or drug screening over the last decade. Despite the wide acceptance in the academic community, their adoption by clinical end-users is still a non-accomplished promise. The reasons behind this difficulty can be very diverse but most likely are related to the lack of predictive power, physiological relevance, and reliability necessary for being utilized in the clinical area. In this Perspective, we briefly discuss the main attributes of organ-on-a-chip platforms in academia and how these characteristics impede their easy translation to the clinic. We also discuss how academia, in conjunction with the industry, can contribute to boosting their adoption by proposing novel design concepts, fabrication methods, processes, and manufacturing materials, improving their standardization and versatility, and simplifying their manipulation and reusability.

Current Trends in Microfluidics and Biosensors for Cancer Research Applications.

Despite the significant amount of resources invested, cancer remains a considerable burden in our modern society and a leading cause of death. There is still a lack of knowledge about the mechanistic determinants of the disease, the mechanism of action of drugs, and the process of tumor relapse. Current methodologies to study all these events fail to provide accurate information, threatening the prognosis of cancer patients. This failure is due to the inadequate procedure in how tumorigenesis is studied and how drug discovery and screening are currently made. Traditionally, they both rely on seeding cells on static flat cultures and on the immunolabelling of cellular structures, which are usually limited in their ability to reproduce the complexity of the native cellular habitat and provide quantitative data. Similarly, more complex animal models are employed for-unsuccessfully-mimicking the human physiology and evaluating the etiology of the disease or the efficacy/toxicity of pharmacological compounds. Despite some breakthroughs and success obtained in understanding the disease and developing novel therapeutic approaches, cancer still kills millions of people worldwide, remaining a global healthcare problem with a high social and economic impact. There is a need for novel integrative methodologies and technologies capable of providing valuable readouts. In this regard, the combination of microfluidics technology with miniaturized biosensors offers unprecedented advantages to accelerate the development of drugs. This integrated technology have the potential to unravel the key pathophysiological processes of cancer progression and metastasis, overcoming the existing gap on in vitro predictive platforms and in vivo model systems. Herein, we discuss how this combination may boost the field of cancer theranostics and drug discovery/screening toward more precise devices with clinical relevance.

From Exosomes to Circulating Tumor Cells: Using Microfluidics to Detect High Predictive Cancer Biomarkers.

Early cancer screening and effective diagnosis is the most effective form to diminish the number of cancer-related deaths. Liquid biopsy constitutes an attractive alternative to tumor biopsy due to its non-invasive nature and sample accessibility, which permits effective screening and patient monitoring. Within the plethora of biomarkers present in circulation, liquid biopsy has mainly been performed by analyzing circulating tumor cells, and more recently, extracellular vesicles. Tracking these biological particles could provide valuable insights into cancer origin, progression, treatment efficacy, and patient prognosis. Microfluidic devices have emerged as viable solutions for point-of-care cancer screening and monitoring due to their user-friendly operation, low operation costs, and capability of processing, quantifying, and analyzing these bioparticles in a single device. However, the size difference between cells and exosomes (micrometer vs nanometer) requires an adaptation of microfluidic isolation approaches, particularly in label-free methodologies governed by particle and fluid mechanics. This chapter will explore the theory behind particle isolation and sorting in different microfluidic techniques necessary to guide researchers into the design and development of such devices.

Emerging Microfluidic and Biosensor Technologies for Improved Cancer Theranostics.

Microfluidics and biosensors have already demonstrated their potential in cancer research. Typical applications of microfluidic devices include the realistic modeling of the tumor microenvironment for mechanistic investigations or the real-time monitoring/screening of drug efficacy. Similarly, point-of-care biosensing platforms are instrumental for the early detection of predictive biomarkers and their accurate quantification. The combination of both technologies offers unprecedented advantages for the management of the disease, with an enormous potential to contribute to improving patient prognosis. Despite their high performance, these methodologies are still encountering obstacles for being adopted by the healthcare market, such as a lack of standardization, reproducibility, or high technical complexity. Therefore, the cancer research community is demanding better tools capable of boosting the efficiency of cancer diagnosis and therapy. During the last years, innovative microfluidic and biosensing technologies, both individually and combined, have emerged to improve cancer theranostics. In this chapter, we discuss how these emerging-and in some cases unconventional-microfluidics and biosensor technologies, tools, and concepts can enhance the predictive power of point-of-care devices and the development of more efficient cancer therapies.

Personalized in vitro Extracellular Matrix Models of Collagen VI-Related Muscular Dystrophies.

Collagen VI-related dystrophies (COL6-RDs) are a group of rare congenital neuromuscular dystrophies that represent a continuum of overlapping clinical phenotypes that go from the milder Bethlem myopathy (BM) to the severe Ullrich congenital muscular dystrophy, for which there is no effective treatment. Mutations in one of the three Collagen VI genes alter the incorporation of this protein into the extracellular matrix (ECM), affecting the assembly and the structural integrity of the whole fibrillar network. Clinical hallmarks of COL6-RDs are secondary to the ECM disruption and include muscle weakness, proximal joint contractures, and distal hyperlaxity. Although some traits have been identified in patients' ECMs, a correlation between the ECM features and the clinical phenotype has not been established, mainly due to the lack of predictive and reliable models of the pathology. Herein, we engineered a new personalized pre-clinical model of COL6-RDs using cell-derived matrices (CDMs) technology to better recapitulate the complexity of the native scenario. We found that CDMs from COL6-RD patients presented alterations in ECM structure and composition, showing a significantly decreased Collagen VI secretion, especially in the more severe phenotypes, and a decrease in Fibrillin-1 inclusion. Next, we examined the Collagen VI-mediated deposition of Fibronectin in the ECM, finding a higher alignment, length, width, and straightness than in patients with COL6-RDs. Overall, these results indicate that CDMs models are promising tools to explore the alterations that arise in the composition and fibrillar architecture due to mutations in Collagen VI genes, especially in early stages of matrix organization. Ultimately, CDMs derived from COL6-RD patients may become relevant pre-clinical models, which may help identifying novel biomarkers to be employed in the clinics and to investigate novel therapeutic targets and treatments.

Providing Spiritual Care to In-Hospital Patients During COVID-19: A Preliminary European Fact-Finding Study.

Historically, there has be a close relationship between the nursing services and spiritual care provision to patients, arising due to the evolvement of many hospitals and nursing programmes from faith-based institutions and religious order nursing. With increasing secularism, these relationships are less entwined. Nonetheless, as nurses typically encounter patients at critical life events, such as receiving bad news or dying, nurses frequently understand the need and requirement for both spiritual support and religious for patients and families during these times. Yet there are uncertainties, and nurses can feel ill-equipped to deal with patients' spiritual needs. Little education or preparation is provided to these nurses, and they often report a lack of confidence within this area. The development of this confidence and the required competencies is important, especially so with increasingly multicultural societies with diverse spiritual and religious needs. In this manuscript, we discuss initial field work carried out in preparation for the development of an Erasmus Plus educational intervention, entitled from Cure to Care Digital Education and Spiritual Assistance in Healthcare. Referring specifically to post-COVID spirituality needs, this development will support nurses to respond to patients' spiritual needs in the hospital setting, using digital means. This preliminary study revealed that while nurses are actively supporting patients' spiritual needs, their education and training are limited, non-standardised and heterogeneous. Additionally, most spiritual support occurs within the context of a Judeo-Christian framework that may not be suitable for diverse faith and non-faith populations. Educational preparation for nurses to provide spiritual care is therefore urgently required.