Noninvasive Vascular Images for Face Transplant Surgical Planning

Objective: Face transplantation replaces substantial defects with anatomically identical donor tissues; preoperative vascular assessment relies on noninvasive imaging to separate and characterize the external carotid vessels and branches. The objective is to describe and illustrate vascular considerations for face transplantation candidates. Methods: Novel noninvasive imaging using computed tomography and magnetic resonance imaging over 3 spatial dimensions plus time was developed and tested in 4 face transplant candidates. Precontrast images assessed bones and underlying metal. Contrast media was used to delineate and separate arteries from veins. For computed tomography, acquisition over multiple time points enabled the computation of tissue perfusion metrics. Time-resolved magnetic resonance angiography was performed to separate arterial and venous phases. Results: The range of circulation times for the external carotid system was 6 to 14 seconds from arterial blush to loss of venous enhancement. Precontrast imaging provided a roadmap of bones and metal. Among the 4 patients, 3 had surgical clips, metal implants, or both within 1 cm of major vessels considered for surgery. Contrast-enhanced wide area detector computed tomographic data acquired in the axial mode separated these structures and provided arterial and venous images for planning the surgical anastomoses. Magnetic resonance imaging was able to distinguish between the large vessels from the external carotid systems. Conclusions: Vascular imaging maps are challenging in face transplantation because of the rapid circulation times and artifact from the initial injury, prior reconstructive attempts, or both. Nevertheless, face transplant candidates require high spatial and temporal resolution vascular imaging to determine those vessels appropriate for surgical anastomoses

Integrating GWAS and Transcriptomics to Identify the Molecular Underpinnings of Thermal Stress Responses in \u3cem\u3eDrosophila melanogaster\u3c/em\u3e

Thermal tolerance of an organism depends on both the ability to dynamically adjust to a thermal stress and preparatory developmental processes that enhance thermal resistance. However, the extent to which standing genetic variation in thermal tolerance alleles influence dynamic stress responses vs. preparatory processes is unknown. Here, using the model species Drosophila melanogaster, we used a combination of Genome Wide Association mapping (GWAS) and transcriptomic profiling to characterize whether genes associated with thermal tolerance are primarily involved in dynamic stress responses or preparatory processes that influence physiological condition at the time of thermal stress. To test our hypotheses, we measured the critical thermal minimum (CTmin) and critical thermal maximum (CTmax) of 100 lines of the Drosophila Genetic Reference Panel (DGRP) and used GWAS to identify loci that explain variation in thermal limits. We observed greater variation in lower thermal limits, with CTmin ranging from 1.81 to 8.60°C, while CTmax ranged from 38.74 to 40.64°C. We identified 151 and 99 distinct genes associated with CTmin and CTmax, respectively, and there was strong support that these genes are involved in both dynamic responses to thermal stress and preparatory processes that increase thermal resistance. Many of the genes identified by GWAS were involved in the direct transcriptional response to thermal stress (72/151 for cold; 59/99 for heat), and overall GWAS candidates were more likely to be differentially expressed than other genes. Further, several GWAS candidates were regulatory genes that may participate in the regulation of stress responses, and gene ontologies related to development and morphogenesis were enriched, suggesting many of these genes influence thermal tolerance through effects on development and physiological status. Overall, our results suggest that thermal tolerance alleles can influence both dynamic plastic responses to thermal stress and preparatory processes that improve thermal resistance. These results also have utility for directly comparing GWAS and transcriptomic approaches for identifying candidate genes associated with thermal tolerance

Embedding mentoring to support trial processes and implementation fidelity in a randomised controlled trial of vocational rehabilitation for stroke survivors

Background: Little guidance exists regarding how best to upskill and support those delivering complex healthcareinterventions to ensure robust trial outcomes and implementation fidelity. Mentoring was provided to occupationaltherapists (OTs) delivering a complex vocational rehabilitation (VR) intervention to stroke survivors. This study aimedto explore mentors’ roles in supporting OTs with intervention delivery and fidelity, and to describe factors affectingthe mentoring process and intervention delivery.Methods: Quantitative data (duration, mode and total time of mentoring support) was extracted from mentoringrecords and emails between mentors and OTs, alongside qualitative data on barriers and facilitators to interventiondelivery. Semi-structured interviews with mentors (n = 6) and OTs (n = 19) explored experiences and perceptions ofintervention training, delivery and the mentoring process. Mean total and monthly time spent mentoring werecalculated per trial site. Qualitative data were analysed thematically.Results: Forty-one OTs across 16 sites were mentored between March 2018 and April 2020. Most mentoring wasprovided by phone or Microsoft Teams (range: 88.6–100%), with the remainder via email and SMS (Short MessageService) text messages. Mentors suggested strategies to enhance trial recruitment, improved OTs’ understanding ofandadherence to trial processes, intervention delivery and fidelity, and facilitated independent problem-solving.Barriers to mentoring included OT non-attendance at mentoring sessions and mentors struggling to balancementoring with clinical roles. Facilitators included support from the trial team and mentors having protected timefor mentoring.Conclusions: Mentoring supported mentee OTs in various ways, but it remains unclear to what extent the OTSwould have been able to deliver the intervention without mentoring support, or how this might have impactedfidelity. Successful implementation of mentoring alongside new complex interventions may increase the likelihoodof intervention effectiveness being observed and sustained in real-life contexts. Further research is needed toinvestigate how mentors could be selected, upskilled, funded and mentoring provided to maximise impact. Theclinical- and cost-effectiveness of mentoring as an implementation strategy and its impact on fidelity also requirestesting in a future trial

Integrating tropical research into biology education is urgently needed

Understanding tropical biology is important for solving complex problems such as climate change, biodiversity loss, and zoonotic pandemics, but biology curricula view research mostly via a temperatezone lens. Integrating tropical research into biology education is urgently needed to tackle these issues. The tropics are engines of Earth systems that regulate global cycles of carbon and water, and are thus critical for management of greenhouse gases. Compared with higher-latitude areas, tropical regions contain a greater diversity of biomes, organisms, and complexity of biological interactions. The tropics house the majority of the world’s human population and provide important global commodities from species that originated there: coffee, chocolate, palm oil, and species that yield the cancer drugs vincristine and vinblastine. Tropical regions, especially biodiversity hotspots, harbor zoonoses, thereby having an important role in emerging infectious diseases amidst the complex interactions of global environmental change and wildlife migration [1]. These well-known roles are oversimplified, but serve to highlight the global biological importance of tropical systems. Despite the importance of tropical regions, biology curricula worldwide generally lack coverage of tropical research. Given logistical, economic, or other barriers, it is difficult for undergraduate biology instructors to provide their students with field-based experience in tropical biology research in a diverse range of settings, an issue exacerbated by the Coronavirus Disease 2019 (COVID-19) pandemic. Even in the tropics, field-based experience may be limited to home regions. When tropical biology is introduced in curricula, it is often through a temperate- zone lens that does not do justice to the distinct ecosystems, sociopolitical histories, and conservation issues that exist across tropical countries and regions [2]. The tropics are often caricatured as distant locations known for their remarkable biodiversity, complicated species interactions, and unchecked deforestation. This presentation, often originating from a colonial and culturally biased perspective, may fail to highlight the role of tropical ecosystems in global environmental and social challenges that accompany rising temperatures, worldwide biodiversity loss, zoonotic pandemics, and the environmental costs of ensuring food, water, and other ecosystem services for humans [3]

PROPHETIC: Prospective Identification of Pneumonia in Hospitalized Patients in the Intensive Care Unit

BACKGROUND: Pneumonia is the leading infection-related cause of death. Using simple clinical criteria and contemporary epidemiology to identify patients at high risk of nosocomial pneumonia should enhance prevention efforts and facilitate development of new treatments in clinical trials. RESEARCH QUESTION: What are the clinical criteria and contemporary epidemiology trends helpful in identifying patients at high risk of nosocomial pneumonia? STUDY DESIGN AND METHODS: Within the intensive care units of 28 United States hospitals, we conducted a prospective cohort study among adults hospitalized more than 48 hours and considered high risk for pneumonia (defined as treatment with invasive or noninvasive ventilatory support or high levels of supplemental oxygen). We estimated the proportion of high-risk patients developing nosocomial pneumonia. Using multivariable logistic regression, we identified patient characteristics and treatment exposures associated with increased risk of pneumonia development during the intensive care unit admission. RESULTS: Between February 6, 2016 and October 7, 2016, 4613 high-risk patients were enrolled. Among 1464/4613 (32%) high-risk patients treated for possible nosocomial pneumonia, 537/1464 (37%) met the study pneumonia definition. Among high-risk patients, a multivariable logistic model was developed to identify key patient characteristics and treatment exposures associated with increased risk of nosocomial pneumonia development (c-statistic 0.709, 95% confidence interval 0.686 to 0.731). Key factors associated with increased odds of nosocomial pneumonia included an admission diagnosis of trauma or cerebrovascular accident, receipt of enteral nutrition, documented aspiration risk, and receipt of systemic antibacterials within the preceding 90 days. INTERPRETATION: Treatment for nosocomial pneumonia is common among intensive care unit patients receiving high levels of respiratory support, yet more than half of patients treated do not fulfill standard diagnostic criteria for pneumonia. Application of simple clinical criteria may improve the feasibility of clinical trials of pneumonia prevention and treatment by facilitating prospective identification of patients at highest risk

Rare causes of scoliosis and spine deformity: experience and particular features

<p>Abstract</p> <p>Background</p> <p>Spine deformity can be idiopathic (more than 80% of cases), neuromuscular, congenital or neurofibromatosis-related. However, there are many disorders that may also be involved. We present our experience treating patients with scoliosis or other spine deformities related to rare clinical entities.</p> <p>Methods</p> <p>A retrospective study of the records of a school-screening study in North-West Greece was performed, covering a 10-year period (1992–2002). The records were searched for patients with deformities related to rare disorders. These patients were reviewed as regards to characteristics of underlying disorder and spine deformity, treatment and results, complications, intraoperative and anaesthesiologic difficulties particular to each case.</p> <p>Results</p> <p>In 13 cases, the spine deformity presented in relation to rare disorders. The underlying disorder was rare neurological disease in 2 cases (Rett syndrome, progressive hemidystonia), muscular disorders (facioscapulohumeral muscular dystrophy, arthrogryposis) in 2 patients, osteogenesis imperfecta in 2 cases, Marfan syndrome, osteopetrosis tarda, spondyloepiphyseal dysplasia congenita, cleidocranial dysplasia and Noonan syndrome in 1 case each. In 2 cases scoliosis was related to other congenital anomalies (phocomelia, blindness). Nine of these patients were surgically treated. Surgery was avoided in 3 patients.</p> <p>Conclusion</p> <p>This study illustrates the fact that different disorders are related with curves with different characteristics, different accompanying problems and possible complications. Investigation and understanding of the underlying pathology is an essential part of the clinical evaluation and preoperative work-up, as clinical experience at any specific center is limited.</p

Dextran-Coated Magnetic Supports Modified with a Biomimetic Ligand for IgG Purification

The authors thank the financial support from Fundacao para a Ciencia e a Tecnologia through Grant PEst-C/EQB/LA0006/2011 and contracts no. PTDC/EBB-BIO/102163/2008, PTDC/EBB-BIO/098961/2008, PTDC/EBB-BIO/118317/2010, SFRH/BD/72650/2010 for V.L.D, and Santander Totta Bank - Universidade Nova de Lisboa for the Scientific Award 2009/2010. The authors are grateful to Dr. Abid Hussain and M. Telma Barroso (REQUIMTE, FCT-UNL, Portugal) for the preparation of the synthetic affinity ligands, to Lonza Biologics, U.K. (Dr. Richard Alldread), and the Animal Cell Technology Unit of ITQB-UNL/IBET (Dr. Paula M Alves and Dr. Ana Teixeira) for providing the cells and the culture bulks and to Mr. Filipe Cardoso and Prof. Paulo Freitas (INESC-MN, Lisbon, Portugal) for the help with the VSM measurements.Dextran-coated iron oxide magnetic particles modified with ligand 22/8, a protein A mimetic ligand, were prepared and assessed for IgG purification. Dextran was chosen as the agent to modify the surface of magnetic particles by presenting a negligible level of nonspecific adsorption. For the functionalization of the particles with the affinity ligand toward antibodies, three methods have been explored. The optimum coupling method yielded a theoretical maximum capacity for human IgG calculated as 568 ± 33 mg/g and a binding affinity constant of 7.7 × 10⁴ M⁻¹. Regeneration, recycle and reuse of particles was also highly successful for five cycles with minor loss of capacity. Moreover, this support presented specificity and effectiveness for IgG adsorption and elution at pH 11 directly from crude extracts with a final purity of 95% in the eluted fraction.proofpublishe

Genomic, Pathway Network, and Immunologic Features Distinguishing Squamous Carcinomas

This integrated, multiplatform PanCancer Atlas study co-mapped and identified distinguishing molecular features of squamous cell carcinomas (SCCs) from five sites associated with smokin

Pan-Cancer Analysis of lncRNA Regulation Supports Their Targeting of Cancer Genes in Each Tumor Context

Long noncoding RNAs (lncRNAs) are commonly dys-regulated in tumors, but only a handful are known toplay pathophysiological roles in cancer. We inferredlncRNAs that dysregulate cancer pathways, onco-genes, and tumor suppressors (cancer genes) bymodeling their effects on the activity of transcriptionfactors, RNA-binding proteins, and microRNAs in5,185 TCGA tumors and 1,019 ENCODE assays.Our predictions included hundreds of candidateonco- and tumor-suppressor lncRNAs (cancerlncRNAs) whose somatic alterations account for thedysregulation of dozens of cancer genes and path-ways in each of 14 tumor contexts. To demonstrateproof of concept, we showed that perturbations tar-geting OIP5-AS1 (an inferred tumor suppressor) andTUG1 and WT1-AS (inferred onco-lncRNAs) dysre-gulated cancer genes and altered proliferation ofbreast and gynecologic cancer cells. Our analysis in-dicates that, although most lncRNAs are dysregu-lated in a tumor-specific manner, some, includingOIP5-AS1, TUG1, NEAT1, MEG3, and TSIX, synergis-tically dysregulate cancer pathways in multiple tumorcontexts