Passive sensitization of human airways induces myogenic contractile responses in vitro

We assessed effects of passive sensitization on human bronchial smooth muscle (BSM) response to mechanical stretching in vitro. Bronchial rings were sham (control) or passively sensitized overnight by using sera from donors demonstrating sensitivity to Dermatophagoides farinae and having immunoglobulin E (IgE) concentrations of 2,600 +/- 200 U/ml. Tissues were fixed isometrically to force transducers to measure responses to electrical field stimulation (EFS) and quick stretch (QS). The myogenic response to QS was normalized to the maximal response to EFS (%EFS). The myogenic response of sensitized BSM was 47.9 +/- 10.9 %EFS to a QS of approximately 6.5% optimal length (Lo); sham-sensitized tissues had a myogenic response of 13.5 +/- 6.4 %EFS (P = 0.012 vs. passively sensitized). A QS of approximately 13% Lo in sensitized BSM caused a response of 82.8 +/- 20.9 %EFS; sham-sensitized tissues developed a response of 38.2 +/- 17.3 %EFS (P = 0.004). BSM incubated with serum from nonallergic donors did not demonstrate increased QS response (4.6 +/- 1.4 %EFS, P = not significant vs. tissue exposed to atopic sera). However, tissues incubated in sera from nonatopic donors supplemented with hapten-specific chimeric IgE (JW8) demonstrated augmented myogenic response to QS of approximately 6.5% Lo (21.9 +/- 6.2 %EFS, P = 0. 027 vs. nonatopic sera alone). We demonstrate that passive sensitization of human BSM preparations causes induction and augmentation of myogenic contractions to QS; this hyperresponsiveness corresponds to the IgE concentration in sensitizing sera.     

Noble Metal Ion-Directed Assembly of 2D Materials for Heterostructured Catalysts and Metallic Micro-Texturing

Assembling 2D-material (2DM) nanosheets into micro- and macro-architectures with augmented functionalities requires effective strategies to overcome nanosheet restacking. Conventional assembly approaches involve external binders and/or functionalization, which inevitably sacrifice 2DM's nanoscale properties. Noble metal ions (NMI) are promising ionic crosslinkers, which can simultaneously assemble 2DM nanosheets and induce synergistic properties. Herein, a collection of NMI–2DM complexes are screened and categorized into two sub-groups. Based on the zeta potentials, two assembly approaches are developed to obtain 1) NMI-crosslinked 2DM hydrogels/aerogels for heterostructured catalysts and 2) NMI–2DM inks for templated synthesis. First, tetraammineplatinum(II) nitrate (TPtN) serves as an efficient ionic crosslinker to agglomerate various 2DM dispersions. By utilizing micro-textured assembly platforms, various TPtN–2DM hydrogels are fabricated in a scalable fashion. Afterward, these hydrogels are lyophilized and thermally reduced to synthesize Pt-decorated 2DM aerogels (Pt@2DM). The Pt@2DM heterostructures demonstrate high, substrate-dependent catalytic activities and promote different reaction pathways in the hydrogenation of 3-nitrostyrene. Second, PtCl₄ can be incorporated into 2DM dispersions at high NMI molarities to prepare a series of PtCl₄–2DM inks with high colloidal stability. By adopting the PtCl₄–graphene oxide ink, various Pt micro-structures with replicated topographies are synthesized with accurate control of grain sizes and porosities.     

Escherichia coli growth under modeled reduced gravity

Bacteria exhibit varying responses to modeled reduced gravity that can be simulated by clino-rotation. When Escherichia coli was subjected to different rotation speeds during clino-rotation, significant differences between modeled reduced gravity and normal gravity controls were observed only at higher speeds (30-50 rpm). There was no apparent affect of removing samples on the results obtained. When E. coli was grown in minimal medium (at 40 rpm), cell size was not affected by modeled reduced gravity and there were few differences in cell numbers. However, in higher nutrient conditions (i.e., dilute nutrient broth), total cell numbers were higher and cells were smaller under reduced gravity compared to normal gravity controls. Overall, the responses to modeled reduced gravity varied with nutrient conditions; larger surface to volume ratios may help compensate for the zone of nutrient depletion around the cells under modeled reduced gravity.     

Improving breastfeeding support: a community health improvement project

BACKGROUND: Because of the brevity of the postpartum hospital stay, mothers and their newborns are discharged home before breastfeeding is well established. In 1992, feedback from patients who had given birth at Fletcher Allen Health Care (Burlington, VT) suggested a need for more consistent, expert, and timely assistance with breastfeeding in the hospital and better continuity of care during the first few weeks at home. QUALITY IMPROVEMENT TEAM: In 1993 a team developed objectives, analyzed the problem and possible solutions, and made eight recommendations on how the hospital could do more to promote breastfeeding. Implementation by team members and hospital staff included policy development, staff education, acquisition of funding, a visiting professorship, development of a lactation consultant coordinator and team, and patient surveys to evaluate the program. A late 1994 survey of 63 postpartum patients on their day of discharge indicated a high level of satisfaction with breastfeeding support in the hospital. CURRENT STATUS: Activities are being undertaken for lactation consultation coverage, further policy development, implementation of nurse competency validation, improved patient and family education materials, and continued evaluation of the breastfeeding support program through patient surveys. CONCLUSION: In the face of barriers such as the project's large scope, a paucity of internal team members, and a large number and variety of recommendations, some of the recommendations and follow-up plans have yet to be implemented. Yet the project has yielded improvements in care and provides a model of how hospitals can expand their traditional boundaries of care and quality improvement into community health issues.     

Heterogeneity of cognitive style among depressed inpatients.

An inference from the cognitive theories of depression is that only a subset of depressed individuals should exhibit distinctively negative cognitive styles. Although this inference has been supported by previous research, attempts to characterize these depressives have yielded few identifying variables. This study of psychiatric inpatients and normal control subjects identified several characteristics of depressives with very negative cognitive styles by (a) examining traditional depression subtypes, (b) grouping depressives on the basis of clinical observations, and (c) asking whether sex, developmental events, and history and severity of depression predict cognitive styles. We found that borderline personality disorder, negative family dynamics during childhood, a history of sexual abuse, and severity of depression predict cognitive styles. We speculate that aversive developmental events may contribute to cognitive vulnerability to depression. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Building a drug development database: challenges in reliable data availability

Abstract

Context: Policy and legislative efforts to improve the biomedical innovation process must rely on a detailed and thorough analysis of drug development and industry output.

Objective: As part of our efforts to build a publicly-available database on the characteristics of drug development, we present work undertaken to test methods for compiling data from public sources. These initial steps are designed to explore challenges in data extraction, completeness and reliability. Specifically, filing dates for Investigational New Drugs (IND) applications with the U.S. Food and Drug Administration (FDA) were chosen as the initial objective data element to be collected.

Materials and methods: FDA’s Drugs@FDA database and the Federal Register (FR) were used to collect IND dates for the 587 New Molecular Entities (NMEs) approved between 1994 and 2014. When available, the following data were captured: approval date, IND number, IND date and source of information.

Results: At least one IND date was available for 445 (75.8%) of the 587 NMEs. The Drugs@FDA database provided IND dates for 303 (51.6%) NMEs and the FR contributed with 297 (50.6%) IND dates. Out of the 445 NMEs for which an IND date was obtained, 274 (61.6%) had more than one date reported.

Discussion: Key finding of this paper is a considerable inconsistency in reliably available or reported data elements, in this particular case, IND application filing dates as assembled from publicly-available sources.

Conclusion: Our team will continue to focus on finding ways to collect relevant information to measure impact of drug innovation.     

Changes in Gene Expression of E. coli under Conditions of Modeled Reduced Gravity

Relatively few studies have examined bacterial responses to the reduced gravity conditions that are experienced by bacteria grown in space. In this study, whole genome expression of Escherichia coli K12 under clinorotation (which models some of the conditions found under reduced gravity) was analyzed. We hypothesized that phenotypic differences at cellular and population levels under clinorotation (hereafter referred to as modeled reduced gravity) are directly coupled to changes in gene expression. Further, we hypothesized that these responses may be due to indirect effects of these environmental conditions on nutrient accessibility for bacteria. Overall, 430 genes were identified as significantly different between modeled reduced gravity conditions and controls. Up-regulated genes included those involved in the starvation response (csiD, cspD, ygaF, gabDTP, ygiG, fliY, cysK) and redirecting metabolism under starvation (ddpX, acs, actP, gdhA); responses to multiple stresses, such as acid stress (asr, yhiW), osmotic stress (yehZYW), oxidative stress (katE, btuDE); biofilm formation (lldR, lamB, yneA, fadB, ydeY); curli biosynthesis (csgDEF), and lipid biosynthesis (yfbEFG). Our results support the previously proposed hypothesis that under conditions of modeled reduced gravity, zones of nutrient depletion develop around bacteria eliciting responses similar to entrance into stationary phase which is generally characterized by expression of starvation inducible genes and genes associated with multiple stress responses.