Transgelin is a TGFβ-inducible gene that regulates osteoblastic and adipogenic differentiation of human skeletal stem cells through actin cytoskeleston organization

Regenerative medicine is a novel approach for treating conditions in which enhanced bone regeneration is required. We identified transgelin (TAGLN), a transforming growth factor beta (TGFβ)-inducible gene, as an upregulated gene during in vitro osteoblastic and adipocytic differentiation of human bone marrow-derived stromal (skeletal) stem cells (hMSC). siRNA-mediated gene silencing of TAGLN impaired lineage differentiation into osteoblasts and adipocytes but enhanced cell proliferation. Additional functional studies revealed that TAGLN deficiency impaired hMSC cell motility and in vitro transwell cell migration. On the other hand, TAGLN overexpression reduced hMSC cell proliferation, but enhanced cell migration, osteoblastic and adipocytic differentiation, and in vivo bone formation. In addition, deficiency or overexpression of TAGLN in hMSC was associated with significant changes in cellular and nuclear morphology and cytoplasmic organelle composition as demonstrated by high content imaging and transmission electron microscopy that revealed pronounced alterations in the distribution of the actin filament and changes in cytoskeletal organization. Molecular signature of TAGLN-deficient hMSC showed that several genes and genetic pathways associated with cell differentiation, including regulation of actin cytoskeleton and focal adhesion pathways, were downregulated. Our data demonstrate that TAGLN has a role in generating committed progenitor cells from undifferentiated hMSC by regulating cytoskeleton organization. Targeting TAGLN is a plausible approach to enrich for committed hMSC cells needed for regenerative medicine application

The Teaching and Learning Cultural Competence in a Multicultural Environment (CCMEn) Model

Background: Within the European higher education context, students and lecturers are encouraged to engage in teaching and learning activities abroad. This frequently involves using a second language and being exposed to students and lecturers from culturally different backgrounds. Objective: To design a model for teaching and learning cultural competence in a multicultural environment (CCMEn). Design: Theory development from empirical experience, research, and scholarly works. Method: This model was developed based on our experience of teaching and learning cultural competence in a multicultural environment in a nursing education context; it rests on three pillars, namely, Coyle's Content and Language Integrated Learning educational approach, the concept of social and emotional learning, as defined by the Collaborative for Academic, Social and Emotional Learning, and the existing literature surrounding teaching and learning cultural competence in higher education. Results: The CCMEn model is intended to guide the process of teaching and learning cultural competence in a multicultural environment through the use of a second language and has been adapted from existing educational approaches and theory. Conclusion: Teaching and learning in multilingual and multicultural contexts in Europe is becoming more common. Students who learn alongside students and teachers from different cultural backgrounds need to be supported from an academic, linguistic and socioemotional perspective. We believe that the CCMEn model can serve as a guide to enhancing student learning in this context

The Palomar Transient Factory: System Overview, Performance and First Results

The Palomar Transient Factory (PTF) is a fully-automated, wide-field survey aimed at a systematic exploration of the optical transient sky. The transient survey is performed using a new 8.1 square degree camera installed on the 48-inch Samuel Oschin telescope at Palomar Observatory; colors and light curves for detected transients are obtained with the automated Palomar 60-inch telescope. PTF uses eighty percent of the 1.2-m and fifty percent of the 1.5-m telescope time. With an exposure of 60-s the survey reaches a depth of approximately 21.3 in g' and 20.6 in R (5 sigma, median seeing). Four major experiments are planned for the five-year project: 1) a 5-day cadence supernova search; 2) a rapid transient search with cadences between 90 seconds and 1 day; 3) a search for eclipsing binaries and transiting planets in Orion; and 4) a 3-pi sr deep H-alpha survey. PTF provides automatic, realtime transient classification and follow up, as well as a database including every source detected in each frame. This paper summarizes the PTF project, including several months of on-sky performance tests of the new survey camera, the observing plans and the data reduction strategy. We conclude by detailing the first 51 PTF optical transient detections, found in commissioning data.Comment: 12 pages, 11 figures, 3 tables, submitted to PAS

Nursing students’ experience of learning cultural competence

Introduction European societies are rapidly becoming multicultural. Cultural diversity presents new challenges and opportunities to communities that receive immigrants and migrants, and highlights the need for culturally safe healthcare. Universities share a responsibility to build a fair and equitable society by integrating cultural content in the nursing curricula. This paper aims to analyze European student nurses´ experience of learning cultural competence and of working with patients from diverse cultural backgrounds. Materials and methods A phenomenological approach was selected through a qualitative research method. 7 semi-structured focus groups with 5–7 students took place at the participants’ respective universities in Spain, Belgium, Turkey and Portugal. Results 5 themes and 16 subthemes emerged from thematic analysis. Theme 1, concept of culture/ cultural diversity, describes the participants’ concept of culture; ethnocentricity emerged as a frequent element in the students’ discourse. Theme 2, personal awareness, integrates the students’ self-perception of cultural competence and their learning needs. Theme 3, impact of culture, delves on the participants’ perceived impact of cultural on both nursing care and patient outcomes. Theme 4, learning cultural competence, integrates the participants’ learning experiences as part of their nursing curricula, as part of other academic learning opportunities and as part of extra-academic activities. Theme 5, learning cultural competence during practice placements, addresses some important issues including witnessing unequal care, racism, prejudice and conflict, communication and language barriers, tools and resources and positive attitudes and behaviors witnesses or displayed during clinical practice. Conclusion The participants’ perceived level of cultural competence was variable. All the participants agreed that transcultural nursing content should be integrated in the nursing curricula, and suggested different strategies to improve their knowledge, skills and attitudes. It is important to listen to the students and take their opinion into account when designing cultural teaching and learning activities. © 2021 Antón-Solanas et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited

Nursing lecturers’ perception and experience of teaching cultural competence: a european qualitative study

Cultural competence is an essential component in providing effective and culturally responsive healthcare services, reducing health inequalities, challenging racism in health care and improving patient safety, satisfaction and health outcomes. It is thus reasonable that undergraduate nursing students can develop cultural competency through education and training. The aim of this paper was to investigate nursing lecturers’ perception and experience of teaching cultural competence in four undergraduate nursing programs. A phenomenological approach was selected to illicit nursing lecturers’ perception of culture and experience of teaching cultural competence. Semi-struc-tured personal interviews were held with a sample of 24 lecturers from four European universities. The anonymized transcripts were analyzed qualitatively following Braun and Clark’s phases for thematic analysis. Six themes and fifteen subthemes emerged from thematic analysis of the tran-scripts. Cultural competence was not explicitly integrated in the nursing curricula. Instead, the lecturers used mainly examples and case studies to illustrate the theory. The integration of cultural content in the modules was unplanned and not based on a specific model. Nursing programs should be examined to establish how cultural content is integrated in the curricula; clear guidelines and standards for a systematic integration of cultural content in the nursing curriculum should be de-veloped

Ocular inflammatory events following COVID-19 vaccination: a multinational case series

Background: Inflammatory adverse events following COVID-19 vaccination are being reported amidst the growing concerns regarding vaccine’s immunogenicity and safety, especially in patients with pre-existing inflammatory conditions. Methods: Multinational case series of patients diagnosed with an ocular inflammatory event within 14 days following COVID-19 vaccination collected from 40 centres over a 3 month period in 2021. Results: Seventy patients presented with ocular inflammatory events within 14 days following COVID-19 vaccination. The mean age was 51 years (range, 19–84 years). The most common events were anterior uveitis (n = 41, 58.6%), followed by posterior uveitis (n = 9, 12.9%) and scleritis (n = 7, 10.0%). The mean time to event was 5 days and 6 days (range, 1–14 days) after the first and second dose of vaccine, respectively. Among all patients, 36 (54.1%) had a previous history of ocular inflammatory event. Most patients (n = 48, 68.6%) were managed with topical corticosteroids. Final vision was not affected in 65 (92.9%), whereas 2 (2.9%) and 3 (4.3%) had reduction in visual acuity reduced by ≤3 lines and > 3 lines, respectively. Reported complications included nummular corneal lesions (n = 1, 1.4%), cystoid macular oedema (n = 2, 2.9%) and macular scarring (n = 2, 2.9%). Conclusion: Ocular inflammatory events may occur after COVID-19 vaccination. The findings are based on a temporal association that does not prove causality. Even in the possibility of a causal association, most of the events were mild and had a good visual outcome

Theoretical Criteria for Scattering Dark States in Nanostructured Particles

Nanostructures with multiple resonances can exhibit a suppressed or even completely eliminated scattering of light, called a scattering dark state. We describe this phenomenon with a general treatment of light scattering from a multiresonant nanostructure that is spherical or nonspherical but subwavelength in size. With multiple resonances in the same channel (i.e., same angular momentum and polarization), coherent interference always leads to scattering dark states in the low-absorption limit, regardless of the system details. The coupling between resonances is inevitable and can be interpreted as arising from far-field or near-field. This is a realization of coupled-resonator-induced transparency in the context of light scattering, which is related to but different from Fano resonances. Explicit examples are given to illustrate these concepts.Massachusetts Institute of Technology. Institute for Soldier Nanotechnologies (Contract W911NF-13-D-0001)National Science Foundation (U.S.). Materials Research Science and Engineering Centers (Program) (Grant DMR-0819762

Guidance on Noncorticosteroid Systemic Immunomodulatory Therapy in Noninfectious Uveitis: Fundamentals Of Care for UveitiS (FOCUS) Initiative

Topic: An international, expert-led consensus initiative to develop systematic, evidence-based recommendations for the treatment of noninfectious uveitis in the era of biologics. Clinical Relevance: The availability of biologic agents for the treatment of human eye disease has altered practice patterns for the management of noninfectious uveitis. Current guidelines are insufficient to assure optimal use of noncorticosteroid systemic immunomodulatory agents. Methods: An international expert steering committee comprising 9 uveitis specialists (including both ophthalmologists and rheumatologists) identified clinical questions and, together with 6 bibliographic fellows trained in uveitis, conducted a Preferred Reporting Items for Systematic Reviews and Meta-Analyses protocol systematic review of the literature (English language studies from January 1996 through June 2016; Medline [OVID], the Central Cochrane library, EMBASE, CINAHL, SCOPUS, BIOSIS, and Web of Science). Publications included randomized controlled trials, prospective and retrospective studies with sufficient follow-up, case series with 15 cases or more, peer-reviewed articles, and hand-searched conference abstracts from key conferences. The proposed statements were circulated among 130 international uveitis experts for review. A total of 44 globally representative group members met in late 2016 to refine these guidelines using a modified Delphi technique and assigned Oxford levels of evidence. Results: In total, 10 questions were addressed resulting in 21 evidence-based guidance statements covering the following topics: when to start noncorticosteroid immunomodulatory therapy, including both biologic and nonbiologic agents; what data to collect before treatment; when to modify or withdraw treatment; how to select agents based on individual efficacy and safety profiles; and evidence in specific uveitic conditions. Shared decision-making, communication among providers and safety monitoring also were addressed as part of the recommendations. Pharmacoeconomic considerations were not addressed. Conclusions: Consensus guidelines were developed based on published literature, expert opinion, and practical experience to bridge the gap between clinical needs and medical evidence to support the treatment of patients with noninfectious uveitis with noncorticosteroid immunomodulatory agents

Promoter polymorphism of the erythropoietin gene in severe diabetic eye and kidney complications

Significant morbidity and mortality among patients with diabetes mellitus result largely from a greatly increased incidence of microvascular complications. Proliferative diabetic retinopathy (PDR) and end stage renal disease (ESRD) are two of the most common and severe microvascular complications of diabetes. A high concordance exists in the development of PDR and ESRD in diabetic patients, as well as strong familial aggregation of these complications, suggesting a common underlying genetic mechanism. However, the precise gene(s) and genetic variant(s) involved remain largely unknown. Erythropoietin (EPO) is a potent angiogenic factor observed in the diabetic human and mouse eye. By a combination of case–control association and functional studies, we demonstrate that the T allele of SNP rs1617640 in the promoter of the EPO gene is significantly associated with PDR and ESRD in three European-American cohorts [Utah: P = 1.91 × 10−3; Genetics of Kidneys in Diabetes (GoKinD) Study: P = 2.66 × 10−8; and Boston: P = 2.1 × 10−2]. The EPO concentration in human vitreous body was 7.5-fold higher in normal subjects with the TT risk genotype than in those with the GG genotype. Computational analysis suggests that the risk allele (T) of rs1617640 creates a matrix match with the EVI1/MEL1 or AP1 binding site, accounting for an observed 25-fold enhancement of luciferase reporter expression as compared with the G allele. These results suggest that rs1617640 in the EPO promoter is significantly associated with PDR and ESRD. This study identifies a disease risk-associated gene and potential pathway mediating severe diabetic microvascular complications

Effects of hospital facilities on patient outcomes after cancer surgery: an international, prospective, observational study

Background Early death after cancer surgery is higher in low-income and middle-income countries (LMICs) compared with in high-income countries, yet the impact of facility characteristics on early postoperative outcomes is unknown. The aim of this study was to examine the association between hospital infrastructure, resource availability, and processes on early outcomes after cancer surgery worldwide.Methods A multimethods analysis was performed as part of the GlobalSurg 3 study-a multicentre, international, prospective cohort study of patients who had surgery for breast, colorectal, or gastric cancer. The primary outcomes were 30-day mortality and 30-day major complication rates. Potentially beneficial hospital facilities were identified by variable selection to select those associated with 30-day mortality. Adjusted outcomes were determined using generalised estimating equations to account for patient characteristics and country-income group, with population stratification by hospital.Findings Between April 1, 2018, and April 23, 2019, facility-level data were collected for 9685 patients across 238 hospitals in 66 countries (91 hospitals in 20 high-income countries; 57 hospitals in 19 upper-middle-income countries; and 90 hospitals in 27 low-income to lower-middle-income countries). The availability of five hospital facilities was inversely associated with mortality: ultrasound, CT scanner, critical care unit, opioid analgesia, and oncologist. After adjustment for case-mix and country income group, hospitals with three or fewer of these facilities (62 hospitals, 1294 patients) had higher mortality compared with those with four or five (adjusted odds ratio [OR] 3.85 [95% CI 2.58-5.75]; p<0.0001), with excess mortality predominantly explained by a limited capacity to rescue following the development of major complications (63.0% vs 82.7%; OR 0.35 [0.23-0.53]; p<0.0001). Across LMICs, improvements in hospital facilities would prevent one to three deaths for every 100 patients undergoing surgery for cancer.Interpretation Hospitals with higher levels of infrastructure and resources have better outcomes after cancer surgery, independent of country income. Without urgent strengthening of hospital infrastructure and resources, the reductions in cancer-associated mortality associated with improved access will not be realised