Rhegmatogenous retinal detachment masquerading as exudative panuveitis with intense anterior chamber inflammatory reaction.

Purpose:This is a retrospective case report illustrating the diagnostic and therapeutic challenges associated with a chronic rhegmatogenous retinal detachment masquerading as a severe panuveitis with intense anterior chamber inflammation. We have included clinical features, anterior segment and fundus photography, B-scan ultrasonography, fluorescein angiography, and intraoperative findings. Observations:A 26-year-old male presented with features of unilateral panuveitis: hypotony, anterior segment inflammation (posterior synechiae and anterior chamber cell with fibrin clumping), diffuse choroidal thickening, and retinal detachment. Laboratory investigations for infectious or rheumatologic processes were negative, and empiric systemic corticosteroid therapy was unsuccessful. This prompted suspicion for an alternate primary etiology, and pars plana vitrectomy revealed small retinal breaks as the underlying cause of the retinal detachment and inflammation. Conclusions:Rhegmatogenous retinal detachments are a known cause of intraocular inflammation. Nevertheless, it remains a challenge to recognize retinal breaks in this setting, particularly with robust anterior segment inflammation and posterior findings resembling severe exudative uveitis. Being aware of this unique presentation may prevent delays in diagnosis and have important prognostic implications

A double masked randomised 4-week, placebo-controlled study in the USA, Thailand and Taiwan to compare the efficacy of oral valganciclovir and topical 2% ganciclovir in the treatment of cytomegalovirus anterior uveitis: study protocol.

IntroductionCytomegalovirus (CMV) anterior uveitis is a recognised cause of anterior uveitis in immunocompetent patients and is preventable cause of vision loss. Ocular sequelae include corneal endothelial damage which can cause corneal oedema and failure, as well as glaucoma. Recurrences of inflammation are common and therefore patients are often exposed to long-term therapy. Oral therapy is available in the form of valganciclovir, although with the caveat of systemic side effects such as bone marrow suppression and renal failure necessitating regular interval laboratory monitoring. Recent reports have demonstrated that topical 2% ganciclovir solution may offer promising treatment outcomes in patients with CMV anterior uveitis with superior safety, cost-effectiveness and convenience profiles. An investigation into the relative equipoise of these therapies is warranted for these reasons.Methods and analysisThe Systemic and Topical Control of Cytomegalovirus Anterior uveitis: Treatment Outcomes (STACCATO) trial is designed as a multicentre, block randomised by site, double-masked, placebo-controlled trial comparing the efficacy of oral valganciclovir, 2% topical ganciclovir and placebo in treating PCR-proven CMV anterior uveitis. Participant clinical evaluation will occur at three study time points by a masked study ophthalmologist over a 28-day period to assess resolution of ocular inflammation (secondary outcome). A control group will provide additional information about the possible impact that the infected host's immune response may play in controlling local viral replication. The primary analysis is an analysis of covariance (three arms) correcting for baseline to compare quantitative CMV viral load in the anterior chamber (AC) aqueous fluid before and 7 days after treatment.Ethics and disseminationThe University of California San Francisco Committee on Human Research and the Khon Kaen University Institutional Review Board have given ethical approval. The results of this trial will be presented at local and international meetings and submitted for peer-reviewed journals for publication.Trial registration numberNCT03576898

All-Atomic Molecular Dynamic Studies of Human and Drosophila CDK8: Insights into Their Kinase Domains, the LXXLL Motifs, and Drug Binding Site

Cyclin-dependent kinase 8 (CDK8) and its regulatory partner Cyclin C (CycC) play conserved roles in modulating RNA polymerase II (Pol II)-dependent gene expression. To understand the structure and function relations of CDK8, we analyzed the structures of human and Drosophila CDK8 proteins using molecular dynamics simulations, combined with functional analyses in Drosophila. Specifically, we evaluated the structural differences between hCDK8 and dCDK8 to predict the effects of the LXXLL motif mutation (AQKAA), the P154L mutations, and drug binding on local structures of the CDK8 proteins. First, we have observed that both the LXXLL motif and the kinase activity of CDK8 are required for the normal larval-to-pupal transition in Drosophila. Second, our molecular dynamic analyses have revealed that hCDK8 has higher hydrogen bond occupation of His149-Asp151 and Asp151-Asn156 than dCDK8. Third, the substructure of Asp282, Phe283, Arg285, Thr287 and Cys291 can distinguish human and Drosophila CDK8 structures. In addition, there are two hydrogen bonds in the LXXLL motif: a lower occupation between L312 and L315, and a relatively higher occupation between L312 and L316. Human CDK8 has higher hydrogen bond occupation between L312 and L316 than dCDK8. Moreover, L312, L315 and L316 in the LXXLL motif of CDK8 have the specific pattern of hydrogen bonds and geometries, which could be crucial for the binding to nuclear receptors. Furthermore, the P154L mutation dramatically decreases the hydrogen bond between L312 and L315 in hCDK8, but not in dCDK8. The mutations of P154L and AQKAA modestly alter the local structures around residues 154. Finally, we identified the inhibitor-induced conformational changes of hCDK8, and our results suggest a structural difference in the drug-binding site between hCDK8 and dCDK8. Taken together, these results provide the structural insights into the roles of the LXXLL motif and the kinase activity of CDK8 in vivo

Research Blogs and the Discussion of Scholarly Information

The research blog has become a popular mechanism for the quick discussion of scholarly information. However, unlike peer-reviewed journals, the characteristics of this form of scientific discourse are not well understood, for example in terms of the spread of blogger levels of education, gender and institutional affiliations. In this paper we fill this gap by analyzing a sample of blog posts discussing science via an aggregator called ResearchBlogging.org (RB). ResearchBlogging.org aggregates posts based on peer-reviewed research and allows bloggers to cite their sources in a scholarly manner. We studied the bloggers, blog posts and referenced journals of bloggers who posted at least 20 items. We found that RB bloggers show a preference for papers from high-impact journals and blog mostly about research in the life and behavioral sciences. The most frequently referenced journal sources in the sample were: Science, Nature, PNAS and PLoS One. Most of the bloggers in our sample had active Twitter accounts connected with their blogs, and at least 90% of these accounts connect to at least one other RB-related Twitter account. The average RB blogger in our sample is male, either a graduate student or has been awarded a PhD and blogs under his own name

Global implementation research capacity building to address cardiovascular disease: An assessment of efforts in eight countries

Cardiovascular diseases are the leading causes of morbidity and mortality worldwide, but implementation of evidence-based interventions for risk factors such as hypertension is lacking, particularly in low and middle income countries (LMICs). Building implementation research capacity in LMICs is required to overcome this gap. Members of the Global Research on Implementation and Translation Science (GRIT) Consortium have been collaborating in recent years to establish a research and training infrastructure in dissemination and implementation to improve hypertension care. GRIT includes projects in Ghana, Guatemala, India, Kenya, Malawi, Nepal, Rwanda, and Vietnam. We collected data from each site on capacity building activities using the Potter and Brough (2004) model, mapping formal and informal activities to develop (a) structures, systems and roles, (b) staff and infrastructure, (c) skills, and (d) tools. We captured information about sites’ needs assessments and metrics plus program adaptations due to the COVID-19 pandemic. All sites reported capacity building activities in each layer of the Capacity Pyramid, with the largest number of activities in the Skills and Tools categories, the more technical and easier to implement categories. All sites included formal and informal training to build Skills. All sites included a baseline needs assessment to guide capacity building activities or assess context and inform intervention design. Sites implementing evidence-based hypertension interventions used common implementation science frameworks to evaluate implementation outcomes. Although the COVID-19 pandemic affected timelines and in-person events, all projects were able to pivot and carry out planned activities. Although variability in the activities and methods used existed, GRIT programs used needs assessments to guide locally appropriate design and implementation of capacity building activities. COVID-19 related changes were necessary, but strong collaborations and relationships with health ministries were maintained. The GRIT Consortium is a model for planning capacity building in LMICs

Training in eight low-and middle-income countries: lessons learned from a pilot study using the WHO-TDR dissemination and implementation massive open online course

IntroductionNon-communicable diseases (NCDs) are a leading cause of morbidity and mortality in low-and middle- income countries (LMICs). Despite this, a lack of funding, training and mentorship for NCD investigators in LMICs exists. In an effort to gain knowledge and skills to address these gaps, participants from the Global Research on Implementation and Translation Science (GRIT), a consortium of studies in eight LMICs and their networks, attended the dissemination and implementation (D&I) massive open online course (MOOC) developed by the Special Programme for Research and Training in Tropical Diseases at the World Health Organization to strengthen D&I capacity building. Here, we report on the pilot of this MOOC, which was implemented during the SARS COVID-19 pandemic from April- November 2020.MethodsParticipants completed pre-and post-training questionnaires to assess self-reported D&I competencies, general research skills, and research mentor access and quality. D&I competencies were measured by use of a scale developed for a US-based training program, with change in competency scores assessed by paired t test. We used univariate statistics to analyze the data for all other outcomes.ResultsOf the 247 participants enrolled, 32 (13%) completed all course requirements, 21 (9%) completed the pre-and post-surveys and are included in the analysis. D&I competency scores suggest improvement for those who had complete pre- and post-assessments. Trainee's average score on the full competency scale improved 1.45 points (0–5 scale) from pre- to post-test; all four subscales also showed evidence of improvements. There were small but not significant increases in competencies for grant writing, proposal/ manuscript writing and presentations from pre- to post-test assessment. 40% of trainees reported access to a research mentor and 12% reported access to a D&I specific mentor. Participants reported barriers (e.g., unstable internet access and challenges due to COVID-19) and facilitators (e.g., topical interests, collaboration with colleagues) to completing the MOOC.ConclusionsAlthough COVID-19 affected program usage and completion, the MOOC was feasible. We also had signals of effectiveness, meaning among LMIC participants completing the course, there was improvement in self-report D&I competency scores. Recommendations for future D&I trainings in LMICs include (1) adding more topic specific modules (i.e., NCD research, general research skills) for scalability; (2) fostering more collaboration with participants across LMICs; and (3) establishing partnerships with D&I mentors for course participants

Tras los pasos de la Sílfide. Imaginarios españoles del ballet romántico a la danza moderna

La publicación que tiene la persona lectora entre sus manos realiza un recorrido de cien años de historia de la danza, un camino que toma como punto de partida la cultura visual del Romanticismo y que se ramifica fuera del ámbito geográfico de nuestro país, analizando los rasgos que definen y construyen la danza española y cómo estos se difundieron en los bailes en el extranjero.Las investigaciones contenidas en este libro son resultado del proyecto Tras los pasos de la Sílfide. Una historia de la danza en España, 1836-1936 (PGC2018-093710-A-I00)Peer reviewe

Rhegmatogenous retinal detachment masquerading as exudative panuveitis with intense anterior chamber inflammatory reaction.

PurposeThis is a retrospective case report illustrating the diagnostic and therapeutic challenges associated with a chronic rhegmatogenous retinal detachment masquerading as a severe panuveitis with intense anterior chamber inflammation. We have included clinical features, anterior segment and fundus photography, B-scan ultrasonography, fluorescein angiography, and intraoperative findings.ObservationsA 26-year-old male presented with features of unilateral panuveitis: hypotony, anterior segment inflammation (posterior synechiae and anterior chamber cell with fibrin clumping), diffuse choroidal thickening, and retinal detachment. Laboratory investigations for infectious or rheumatologic processes were negative, and empiric systemic corticosteroid therapy was unsuccessful. This prompted suspicion for an alternate primary etiology, and pars plana vitrectomy revealed small retinal breaks as the underlying cause of the retinal detachment and inflammation.ConclusionsRhegmatogenous retinal detachments are a known cause of intraocular inflammation. Nevertheless, it remains a challenge to recognize retinal breaks in this setting, particularly with robust anterior segment inflammation and posterior findings resembling severe exudative uveitis. Being aware of this unique presentation may prevent delays in diagnosis and have important prognostic implications

Arguing the ethics of facial transplantation.

While 7 face transplants have been performed around the world, to date, there remains debate regarding the validity of this procedure. We submit that performing a facial transplant-in the appropriately selected patient-is technically defensible and ethically sound. By outlining the technical and ethical boundaries of the debate, responding to the key arguments against the procedure, and describing its motivations and potential benefits, we state our justification of facial transplantation