Liquid to solid transition of elastin condensates.

Liquid-liquid phase separation of tropoelastin has long been considered to be an important early step in the complex process of elastin fiber assembly in the body and has inspired the development of elastin-like peptides with a wide range of industrial and biomedical applications. Despite decades of study, the material state of the condensed liquid phase of elastin and its subsequent maturation remain poorly understood. Here, using a model minielastin that mimics the alternating domain structure of full-length tropoelastin, we examine the elastin liquid phase. We combine differential interference contrast (DIC), fluorescence, and scanning electron microscopy with particle-tracking microrheology to resolve the material transition occurring within elastin liquids over time in the absence of exogenous cross-linking. We find that this transition is accompanied by an intermediate stage marked by the coexistence of insoluble solid and dynamic liquid phases giving rise to significant spatial heterogeneities in material properties. We further demonstrate that varying the length of the terminal hydrophobic domains of minielastins can tune the maturation process. This work not only resolves an important step in the hierarchical assembly process of elastogenesis but further contributes mechanistic insight into the diverse repertoire of protein condensate maturation pathways with emerging importance across biology.

Logistic growth modelling of COVID-19 proliferation in China and its international implications.

OBJECTIVE: As the coronavirus disease 2019 (COVID-19) pandemic continues to proliferate globally, this paper shares the findings of modelling the outbreak in China at both provincial and national levels. This paper examines the applicability of the logistic growth model, with implications for the study of the COVID-19 pandemic and other infectious diseases. METHODS: An NLS (Non-Linear Least Squares) method was employed to estimate the parameters of a differentiated logistic growth function using new daily COVID-19 cases in multiple regions in China and in other selected countries. The estimation was based upon training data from January 20, 2020 to March 13, 2020. A restriction test was subsequently implemented to examine whether a designated parameter was identical among regions or countries, and the diagnosis of residuals was also conducted. The model's goodness of fit was checked using testing data from March 14, 2020 to April 18, 2020. RESULTS: The model presented in this paper fitted time-series data exceedingly well for the whole of China, its eleven selected provinces and municipalities, and two other countries - South Korea and Iran - and provided estimates of key parameters. This study rejected the null hypothesis that the growth rates of outbreaks were the same among ten selected non-Hubei provinces in China, as well as between South Korea and Iran. The study found that the model did not provide reliable estimates for countries that were in the early stages of outbreaks. Furthermore, this study concured that the R2 values might vary and mislead when compared between different portions of the same non-linear curve. In addition, the study identified the existence of heteroskedasticity and positive serial correlation within residuals in some provinces and countries. CONCLUSIONS: The findings suggest that there is potential for this model to contribute to better public health policy in combatting COVID-19. The model does so by providing a simple logistic framework for retrospectively analyzing outbreaks in regions that have already experienced a maximal proliferation in cases. Based upon statistical findings, this study also outlines certain challenges in modelling and their implications for the results.

Optic neuropathy caused by naso-orbital mass in chronic intranasal cocaine abuse.

A 48-year-old woman with a history of chronic intranasal cocaine abuse presented with unilateral proptosis associated with severe visual loss from optic neuropathy in the right eye. Imaging showed extensive bone and soft tissue destruction in the paranasal region and an orbital mass. Initial biopsies suggested a low-grade neoplasm. The correct diagnosis was established only on repeat biopsy, which revealed marked pleomorphism and nonspecific chronic inflammation with irregular collagen bundles containing thick-walled blood vessels. This case emphasizes that intranasal cocaine abuse may clinically, radiographically, and histopathologically mimic a neoplasm or a necrotizing vasculitis.

Management of congenital nonpigmented iris cyst.

PURPOSE: Previously reported clinical outcomes after treatment of congenital iris cysts have been poor, complicated by cyst recurrence and vision loss. Our purpose was to evaluate the outcomes of surgical excision and microdiathermy of congenital iris cysts. DESIGN: Interventional retrospective case series. METHODS: Four patients (3 children, 1 adult) were treated for a congenital iris cyst based on history and clinical presentation. After cyst excision with caution to avoid cyst rupture, the base of the cyst was treated with microdiathermy. MAIN OUTCOME MEASURE: Presence or absence of a residual cyst after surgical intervention. RESULTS: In all 4 patients, histopathological findings confirmed the diagnosis of a congenital iris cyst. Follow-up periods ranged from 1.4 to 6.2 years (mean +/- standard deviation, 4+/-2). Vision loss did not occur in any of the treated eyes. No cyst recurrence was noted after initial surgical treatment. CONCLUSION: A modern microsurgical technique with adjunctive use of microdiathermy provides improved outcomes in the surgical management of congenital iris cysts. We believe that microdiathermy applied to the base of the cyst removes residual epithelial tissue that accounted for the recurrences documented in previous reports.

Outcomes from a postgraduate biomedical technology innovation training program: the first 12 years of Stanford Biodesign.

The Stanford Biodesign Program began in 2001 with a mission of helping to train leaders in biomedical technology innovation. A key feature of the program is a full-time postgraduate fellowship where multidisciplinary teams undergo a process of sourcing clinical needs, inventing solutions and planning for implementation of a business strategy. The program places a priority on needs identification, a formal process of selecting, researching and characterizing needs before beginning the process of inventing. Fellows and students from the program have gone on to careers that emphasize technology innovation across industry and academia. Biodesign trainees have started 26 companies within the program that have raised over $200 million and led to the creation of over 500 new jobs. More importantly, although most of these technologies are still at a very early stage, several projects have received regulatory approval and so far more than 150,000 patients have been treated by technologies invented by our trainees. This paper reviews the initial outcomes of the program and discusses lessons learned and future directions in terms of training priorities.

Acute systemic histoplasmosis associated with chorioretinitis in an immunocompetent adolescent.

Histoplasmosis is an endemic, systemic mycosis caused by the dimorphic fungus Histoplasma capsulatum. A minority of patients develop asymptomatic chorioretinitis known as presumed ocular histoplasmosis syndrome (POHS), which is typically associated with chorioretinal scarring and peripapillary atrophy and occasionally with choroidal neovascularization secondary to maculopathy. We report a case of acute severe bilateral chorioretinitis associated with disseminated H. capsulatum in an immunocompetent adolescent boy living in an endemic area. The chorioretinitis did not respond to systemic antifungal therapy, but both his systemic illness and ocular lesions resolved with the addition of systemic steroids.

Trabeculectomy versus Ahmed Glaucoma Valve implantation in neovascular glaucoma.

PURPOSE: To compare surgical outcomes in neovascular glaucoma patients who underwent trabeculectomy with mitomycin C versus Ahmed Glaucoma Valve implantation. PATIENTS AND METHODS: This was a retrospective comparative case series. We reviewed 40 eyes of 39 patients with underlying diagnosis of neovascular glaucoma, divided into two groups: Ahmed Glaucoma Valve (N = 20) and trabeculectomy with mitomycin C (N = 20). Surgical success was defined as 6 mm Hg ≤ intraocular pressure ≤21 mm Hg, with or without the use of glaucoma medications, with no further glaucoma surgery, and light perception or better vision. Early postoperative hypotony was defined as intraocular pressure <5 mm Hg during the first postoperative week. RESULTS: The average follow-up was 31 months (range 6-87 months) for the Ahmed Glaucoma Valve group and 25 months (6-77 months) for the trabeculectomy group. Although the mean number of postoperative intraocular pressure-lowering medications was significantly higher in the trabeculectomy group compared with the Ahmed Glaucoma Valve group at 3 and 6 month time points, there was no statistically significant difference at any other time point. There was no statistically significant difference between both groups in postoperative visual acuity and intraocular pressure. Success was 70% and 65% at 1 year and 60% and 55% at 2 years after Ahmed Glaucoma Valve and trabeculectomy, respectively. Kaplan-Meier survival curve analysis showed no significant difference in success between the two groups (P = 0.815). Hyphema was the most common complication in both groups. CONCLUSION: We found similar results after trabeculectomy with mitomycin C and Ahmed Glaucoma Valve implantation in eyes with neovascular glaucoma.

Bioconjugated quantum dots for multiplexed and quantitative immunohistochemistry.

Bioconjugated quantum dots (QDs) provide a new class of biological labels for evaluating biomolecular signatures (biomarkers) on intact cells and tissue specimens. In particular, the use of multicolor QD probes in immunohistochemistry is considered one of the most important and clinically relevant applications. At present, however, clinical applications of QD-based immunohistochemistry have achieved only limited success. A major bottleneck is the lack of robust protocols to define the key parameters and steps. Here, we describe our recent experience, preliminary results and detailed protocols for QD-antibody conjugation, tissue specimen preparation, multicolor QD staining, image processing and biomarker quantification. The results demonstrate that bioconjugated QDs can be used for multiplexed profiling of molecular biomarkers, and ultimately for correlation with disease progression and response to therapy. In general, QD bioconjugation is completed within 1 day, and multiplexed molecular profiling takes 1-3 days depending on the number of biomarkers and QD probes used.

Plasma adiponectin levels and metabolic factors in nondiabetic adolescents.

OBJECTIVES: The relationship of plasma adiponectin levels with various anthropometric and metabolic factors has been surveyed extensively in adults. However, how plasma adiponectin levels are related to various anthropometric indices and cardiovascular risk factors in adolescents is not as vigorously studied. In this study, we investigated this among healthy nondiabetic adolescents. RESEARCH METHODS AND PROCEDURES: Two hundred thirty nondiabetic subjects (125 boys and 105 girls, approximately 10 to 19 years old) were included. The plasma adiponectin, fasting plasma glucose, insulin, lipids and anthropometric indices including body height, weight, waist circumference, and hip circumference were examined. Body fat mass (FM) and percentage were obtained from DXA scan. The homeostasis model assessment was applied to estimate the degree of insulin resistance. RESULTS: The plasma adiponectin levels were significantly higher in girls (30.79 +/- 14.48 micro g/mL) than boys (22.87 +/- 11.41 micro g/mL). The plasma adiponectin levels were negatively related to BMI, FM, FM percentage, waist circumference, waist-to-hip ratio, insulin resistance, plasma insulin, triglycerides, and uric acid levels, but positively with high-density lipoprotein cholesterol (HDL-C) with the adjustment for age and gender. Using different multivariate linear regression models, only age and HDL-C were consistently related to the plasma adiponectin levels after adjustment for the other variables. DISCUSSION: The relationship between plasma adiponectin and various anthropometric indices and metabolic factors, especially HDL-C, previously reported in adults was present in the healthy nondiabetic adolescents. Whether variation of plasma adiponectin levels in healthy nondiabetic adolescents may influence their future coronary artery disease risk warrants further investigation.

Tumor necrosis factor regulates intestinal epithelial cell migration by receptor-dependent mechanisms.

Altered mucosal integrity and increased cytokine production, including tumor necrosis factor (TNF), are the hallmarks of inflammatory bowel disease (IBD). In this study, we addressed the role of TNF receptors (TNFR) on intestinal epithelial cell migration in an in vitro wound closure model. With mouse TNFR1 or TNFR2 knockout intestinal epithelial cells, gene transfection, and pharmacological inhibitors, we show a concentration-dependent receptor-mediated regulation of intestinal cell migration by TNF. A physiological TNF level (1 ng/ml) enhances migration through TNFR2, whereas a pathological level (100 ng/ml) inhibits wound closure through TNFR1. Increased rate of wound closure by TNFR2 or inhibition by TNFR1 cannot be explained by either increased proliferation or apoptosis, respectively. Furthermore, inhibiting Src tyrosine kinase decreases TNF-induced focal adhesion kinase (FAK) tyrosine phosphorylation and cellular migration. We therefore conclude that TNFR2 activates a novel Src-regulated pathway involving FAK tyrosine phosphorylation that enhances migration of intestinal epithelial cells.