Distention of the Immature Left Ventricle Triggers Development of Endocardial Fibroelastosis: An Animal Model of Endocardial Fibroelastosis Introducing Morphopathological Features of Evolving Fetal Hypoplastic Left Heart Syndrome

Background. Endocardial fibroelastosis (EFE), characterized by a diffuse endocardial thickening through collagen and elastin fibers, develops in the human fetal heart restricting growth of the left ventricle (LV). Recent advances in fetal imaging indicate that EFE development is directly associated with a distended, poorly contractile LV in evolving hypoplastic left heart syndrome (HLHS). In this study, we developed an animal model of EFE by introducing this human fetal LV morphopathology to an immature rat heart. Methods and Results. A neonatal donor heart, in which aortic regurgitation (AR) was created, was heterotopically transplanted into a recipient adult rat. AR successfully induced the LV morphology of evolving HLHS in the transplanted donor hearts, which resulted in the development of significant EFE covering the entire LV cavity within two weeks postoperatively. In contrast, posttransplants with a competent aortic valve displayed unloaded LVs with a trace of EFE. Conclusions. We could show that distention of the immature LV in combination with stagnant flow triggers EFE development in this animal model. This model would serve as a robust tool to develop therapeutic strategies to treat EFE while providing insight into its pathogenesis

Neurophysiologic testing in capsaicin and placebo treated skin.

<p>The cold (a), heat (b), cold-pain (d), and heat-pain (d) detection thresholds are shown for each test visit for placebo (black circles) and capsaicin (open circles) treated regions. Cold detection thresholds were lower for every test day in the capsaicin treated side. Heat and heat-pain detection thresholds were higher for every test day on the capsaicin treated side. No significant differences were noted in cold-pain detection thresholds. Blood flow measured by laser-Doppler flowmetry is shown in (e) for placebo (black circles) and capsaicin (open circles) treated regions. Axon-reflex mediated blood flow was reduced in the capsaicin treated region compared to placebo treated region on all test days except day 28. Sweat volume measured by the quantitative sudomotor axon reflex test (QSART) is shown in (f). Sweat output was reduced in the capsaicin treated region compared to the placebo treated region on all test days except day 1. AUC = area under the curve. *<i>P</i><0.05.</p

The intra-epidermal and sweat gland nerve fiber density in capsaicin and placebo treated skin.

<p>(a) The intra-epidermal nerve fiber density from biopsies taken on day 1 and 14 is shown (mean ± SD). *<i>P</i><0.001 compared to control. (b) The sweat gland nerve fiber density from biopsies taken on day 1 and 14 is shown (mean ± SD). *<i>P</i><0.01 compared to control. (c, e) Protein gene product 9.5 labeled intra-epidermal nerve fibers from day 14 biopsies in placebo (c) and capsaicin (d) treated skin. Black arrows denote intra-epidermal fibers in placebo treated skin (c), but are not seen in capsaicin treated skin (e). (d, f) Protein gene product 9.5 labeled sweat gland nerve fibers from day 14 biopsies in placebo (d) and capsaicin (f) treated skin.</p

Rates of shallow and deep wound healing from capsaicin and placebo treated skin.

<p>Wound healing from day 1 (a & b) and day 14 (c & d) biopsies. Survival curves (a & c) are defined as the time from biopsy to wound closure (percent of biopsies not healed). The area of the open wound at each time point by biopsy type and treatment is shown for day 1 (b) and day 14 (d). Shallow biopsies from capsaicin treated areas healed more slowly than shallow biopsies from placebo treated areas (<i>P</i><0.001 vs. placebo) on day 1 and day 14. There were no differences in capsaicin and placebo treated deep biopsies (<i>P</i> = 0.43 vs. placebo, day 1; <i>P</i> = 0.09 vs. placebo day 14). Shallow biopsies from capsaicin treated areas healed more quickly on day 14 (d) than on day 1 (b) (<i>P</i> = 0.03). Statistical significance is not displayed in these graphs.</p

Skin biopsies as a model of wound healing.

<p>Three millimeter punch skin biopsies from the thigh with a ruler used as an internal standard measurement. The shallow biopsy (shown in subset) on the right contains pieces of hair follicles seen within the wound bed. The deep biopsy (shown in subset) is on the left and contains no remnants of adnexal structures within the wound bed.</p

Feature selection and prediction of treatment failure in tuberculosis

Background: Tuberculosis is a major cause of morbidity and mortality in the developing world. Drug resistance, which is predicted to rise in many countries worldwide, threatens tuberculosis treatment and control. Objective: To identify features associated with treatment failure and to predict which patients are at highest risk of treatment failure. Methods: On a multi-country dataset managed by the National Institute of Allergy and Infectious Diseases we applied various machine learning techniques to identify factors statistically associated with treatment failure and to predict treatment failure based on baseline demographic and clinical characteristics alone. Results: The complete-case analysis database consisted of 587 patients (68% males) with a median (p25-p75) age of 40 (30–51) years. Treatment failure occurred in approximately one fourth of the patients. The features most associated with treatment failure were patterns of drug sensitivity, imaging findings, findings in the microscopy Ziehl-Nielsen stain, education status, and employment status. The most predictive model was forward stepwise selection (AUC: 0.74), although most models performed at or above AUC 0.7. A sensitivity analysis using the 643 original patients filling the missing values with multiple imputation showed similar predictive features and generally increased predictive performance. Conclusion: Machine learning can help to identify patients at higher risk of treatment failure. Closer monitoring of these patients may decrease treatment failure rates and prevent emergence of antibiotic resistance. The use of inexpensive basic demographic and clinical features makes this approach attractive in low and middle-income countries

Bio-Inspired Cryo-Ink Preserves Red Blood Cell Phenotype and Function During Nanoliter Vitrification

Current red blood cell cryopreservation methods utilize bulk volumes, causing cryo-injury of cells, which results in irreversible disruption of cell morphology, mechanics, and function. An innovative approach to preserve human red blood cell morphology, mechanics, and function following vitrification in nanoliter volumes is developed using a novel cryo-ink integrated with a bio-printing approach