Toxic Baby Furniture: The Latest Case for Making Products Safe From the Start

Estimates indoor pollution levels of formaldehyde -- linked to increased risks of allergies, asthma, and cancer -- emitted by cribs, changing tables, and other baby furniture. Makes suggestions for avoiding exposure and for regulatory action

Making Tracks: The Case for Building a 21st Century Transportation Network in Maryland

Outlines how investing in public transit by building a regional rail system, expanding or linking rail and bus lines, and improving transit in smaller towns would reduce traffic, oil dependency, and global warming as well as create healthier communities

Two-color STED microscopy reveals different degrees of colocalization between hexokinase-I and the three human VDAC isoforms

The voltage-dependent anion channel (VDAC, also known as mitochondrial porin) is the major transport channel mediating the transport of metabolites, including ATP, across the mitochondrial outer membrane. Biochemical data demonstrate the binding of the cytosolic protein hexokinase-I to VDAC, facilitating the direct access of hexokinase-I to the transported ATP. In human cells, three hVDAC isoforms have been identified. However, little is known on the distribution of these isoforms within the outer membrane of mitochondria and to what extent they colocalize with hexokinase-I. In this study we show that whereas hVDAC1 and hVDAC2 are localized predominantly within the same distinct domains in the outer membrane, hVDAC3 is mostly uniformly distributed over the surface of the mitochondrion. We used two-color stimulated emission depletion (STED) microscopy enabling a lateral resolution of ~40 nm to determine the detailed sub-mitochondrial distribution of the three hVDAC isoforms and hexokinase-I. Individual hVDAC and hexokinase-I clusters could thus be resolved which were concealed in the confocal images. Quantitative colocalization analysis of two-color STED images demonstrates that within the attained resolution, hexokinase-I and hVDAC3 exhibit a higher degree of colocalization than hexokinase-I with either hVDAC1 or hVDAC2. Furthermore, a substantial fraction of the mitochondria-bound hexokinase-I pool does not colocalize with any of the three hVDAC isoforms, suggesting a more complex interplay of these proteins than previously anticipated. This study demonstrates that two-color STED microscopy in conjunction with quantitative colocalization analysis is a powerful tool to study the complex distribution of membrane proteins in organelles such as mitochondria

Morphology-Dependent Influences on the Performance of Battery Cells with a Hierarchically Structured Positive Electrode

The rising demand for high-performing batteries requires new technological concepts. To facilitate fast charge and discharge, hierarchically structured electrodes offer short diffusion paths in the active material. However, there are still gaps in understanding the influences on the cell performance of such electrodes. Here, we employed a cell model to demonstrate that the morphology of the hierarchically structured electrode determines which electrochemical processes dictate the cell performance. The potentially limiting processes include electronic conductivity within the porous secondary particles, solid diffusion within the primary particles, and ionic transport in the electrolyte surrounding the secondary particles. Our insights enable a goal-oriented tailoring of hierarchically structured electrodes for high-power applications

Morphology‐Dependent Influences on the Performance of Battery Cells with a Hierarchically Structured Positive Electrode**

The rising demand for high-performing batteries requires new technological concepts. To facilitate fast charge and discharge, hierarchically structured electrodes offer short diffusion paths in the active material. However, there are still gaps in understanding the influences on the cell performance of such electrodes. Here, we employed a cell model to demonstrate that the morphology of the hierarchically structured electrode determines which electrochemical processes dictate the cell performance. The potentially limiting processes include electronic conductivity within the porous secondary particles, solid diffusion within the primary particles, and ionic transport in the electrolyte surrounding the secondary particles. Mitigating these limits requires an electronic conductivity in the active material of at least 10−4 S m−1 and a primary particle radius below 100 nm. Our insights enable a goal-oriented tailoring of hierarchically structured electrodes for high-power applications

Value of 3D Reconstructions of CT Scans for Calcaneal Fracture Assessment

Background: The interpretation of CT scans for the evaluation of calcaneal fractures is difficult. Three-dimensional (3D) reconstruction (volume rendering technique [VRT]) has been valuable in the evaluation of irregularly shaped bones. However, their value for the analysis of calcaneal fractures is still debated. Therefore, the objective of this study was to assess the effect of additional use of 3D CTs in calcaneal fractures. Methods: In a prospective multicenter study, the CT data set of 5 different fractures was presented to 57 evaluators. First, the participating surgeons were asked to assess the fractures on the basis of axial, coronal, and sagittal reconstructions using a multiple-choice questionnaire. Second, 3D reconstructions (VRT) were presented. The CT scans were validated by the intraoperative findings and the results were compared to the model solution of 3 foot and ankle surgeons. Intra- and interrater reliabilities were calculated. Results: The proportion of intraobserver agreement was 82%, with Cohen kappa of = 0.748 (P < .001). Interrater agreement varied between 0.772 (P = .006) for the assessment of concomitant fractures and 0.987 (P < .001) for the suggested approach. The evaluation of several items improved after presentation of the 3D CTs (Cochrane Q test, P < .001). The benefit of 3D imaging was higher in inexperienced surgeons and complex fractures (Friedman test P < .001). Conclusion: The evaluation of CT scans of calcaneal fractures was improved by the additional use of 3D images (VRT). Level of Evidence: Level II, prospective comparative study

second line cabozantinib versus nivolumab in advanced renal cell carcinoma systematic review and indirect treatment comparison

Abstract Background Nivolumab and cabozantinib, two new treatment options for previously-treated advanced/metastatic renal cell carcinoma (aRCC), have recently been approved. Methods Two independent reviewers performed study selection, data extraction, and risk of bias assessment. Indirect treatment comparisons were carried out by directly assessing HR differences and statistical modeling of Kaplan-Meier curves from these two trials. Results Publications identified showed that no head-to-head comparisons had been carried out. Two indirect treatment comparisons used agreed that there was no significant difference in OS between cabozantinib and nivolumab and that cabozantinib significantly improved PFS compared to nivolumab. Conclusions The field of aRCC treatments is evolving rapidly, creating opportunities for individualized treatments and challenges for clinicians to keep up with the evidence. In lieu of availability of direct comparisons of all options, advanced modeling results presented herein can help to inform and improve personalized treatments

Model-Informed Target Morning 17α-Hydroxyprogesterone Concentrations in Dried Blood Spots for Pediatric Congenital Adrenal Hyperplasia Patients

Monitoring cortisol replacement therapy in congenital adrenal hyperplasia (CAH) patients is vital to avoid serious adverse events such as adrenal crises due to cortisol underexposure or metabolic consequences due to cortisol overexposure. The less invasive dried blood spot (DBS) sampling is an advantageous alternative to traditional plasma sampling, especially in pediatric patients. However, target concentrations for important disease biomarkers such as 17α-hydroxyprogesterone (17-OHP) are unknown using DBS. Therefore, a modeling and simulation framework, including a pharmacokinetic/pharmacodynamic model linking plasma cortisol concentrations to DBS 17-OHP concentrations, was used to derive a target morning DBS 17-OHP concentration range of 2–8 nmol/L in pediatric CAH patients. Since either capillary or venous DBS sampling is becoming more common in the clinics, the clinical applicability of this work was shown by demonstrating the comparability of capillary and venous cortisol and 17-OHP concentrations collected by DBS sampling, using a Bland-Altman and Passing-Bablok analysis. The derived target morning DBS 17-OHP concentration range is a first step towards providing improved therapy monitoring using DBS sampling and adjusting hydrocortisone (synthetic cortisol) dosing in children with CAH. In the future, this framework can be used to assess further research questions, e.g., target replacement ranges for the entire day

Targeting a cancer-specific LYPD3 glycoform for tumor therapy

Introduction: One of the most drastic changes in cancer is the altered glycosylation of proteins and lipids, giving rise to truncated O-glycans like the Thomsen Friedenreich (TF) or Thomsen nouvelle (Tn) antigen, which are almost absent on normal cells. Combined protein-carbohydrate epitopes comprising these specific glycans are ideal candidates for potent targeted therapies given their excellent tumor specificity and broad cancer expression.Methods and results: We have generated GT-002, a monoclonal antibody specifically targeting the epithelial glycoprotein LYPD3 only in the presence of a TF glycosylation. It does not cross-react with non-glycosylated LYPD3 or TF on other glycoproteins in ELISA and flow cytometry. GT-002 binds to various tumor cell lines and stains tumor tissues of different cancer indications including squamous cell carcinoma of the head and neck. The remarkable tumor specificity was confirmed in an immunohistochemistry study on a normal human tissue panel including several LYPD3-positive organs, where GT-002 elicited almost completely abolished normal tissue binding. Consequently, we observed markedly reduced binding of GT-002 to normal human tissues compared to Lupartumab, a conventional anti-LYPD3 antibody previously in clinical development as antibody-drug conjugate (BAY1129980). Neuraminidase treatment of healthy tissues, resulting in cleavage of sialic acid residues, re-established binding of GT-002 comparable to Lupartumab, showing that the GT-002 epitope is masked by sialic acid in normal cells.Discussion: We believe that GT-002 is a promising candidate for development of antibody-drug- and radio-conjugates as well as bispecific molecules and chimeric antigen receptor therapeutics and highlights the powerful potential of antibodies against combined protein-carbohydrate epitopes to reduce on-target/off-tumor cytotoxicity

Stress Strengthens Memory of First Impressions of Others' Positive Personality Traits

Encounters with strangers bear potential for social conflict and stress, but also allow the formation of alliances. First impressions of other people play a critical role in the formation of alliances, since they provide a learned base to infer the other's future social attitude. Stress can facilitate emotional memories but it is unknown whether stress strengthens our memory for newly acquired impressions of other people's personality traits. To answer this question, we subjected 60 students (37 females, 23 males) to an impression-formation task, viewing portraits together with brief positive vs. negative behavior descriptions, followed by a 3-min cold pressor stress test or a non-stressful control procedure. The next day, novel and old portraits were paired with single trait adjectives, the old portraits with a trait adjective matching the previous day's behavior description. After a filler task, portraits were presented again and subjects were asked to recall the trait adjective. Cued recall was higher for old (previously implied) than the novel portraits' trait adjectives, indicating validity of the applied test procedures. Overall, recall rate of implied trait adjectives did not differ between the stress and the control group. However, while the control group showed a better memory performance for others' implied negative personality traits, the stress group showed enhanced recall for others' implied positive personality traits. This result indicates that post-learning stress affects consolidation of first impressions in a valence-specific manner. We propose that the stress-induced strengthening of memory of others' positive traits forms an important cue for the formation of alliances in stressful conditions