Large production volumes of zinc oxide nanoparticles (ZnONP) might be anticipated to pose risks, of accidental inhalation in occupational and even in consumer settings. Herein, we further ...investigated the pathological changes induced by ZnONP and their possible mechanism of action.
Two doses of ZnONP (50 and 150 cm2/rat) were intratracheally instilled into the lungs of rats with assessments made at 24 h, 1 wk, and 4 wks after instillation to evaluate dose- and time-course responses. Assessments included bronchoalveolar lavage (BAL) fluid analysis, histological analysis, transmission electron microscopy, and IgE and IgA measurement in the serum and BAL fluid. To evaluate the mechanism, alternative ZnONP, ZnONP-free bronchoalveolar lavage exudate, and dissolved Zn2+ (92.5 μg/rat) were also instilled to rats. Acridine orange staining was utilized in macrophages in culture to evaluate the lysosomal membrane destabilization by NP.
ZnONP induced eosinophilia, proliferation of airway epithelial cells, goblet cell hyperplasia, and pulmonary fibrosis. Bronchocentric interstitial pulmonary fibrosis at the chronic phase was associated with increased myofibroblast accumulation and transforming growth factor-β positivity. Serum IgE levels were up-regulated by ZnONP along with the eosinophilia whilst serum IgA levels were down-regulated by ZnONP. ZnONP are rapidly dissolved under acidic conditions (pH 4.5) whilst they remained intact around neutrality (pH 7.4). The instillation of dissolved Zn2+ into rat lungs showed similar pathologies (eg., eosinophilia, bronchocentric interstitial fibrosis) as were elicited by ZnONP. Lysosomal stability was decreased and cell death resulted following treatment of macrophages with ZnONP in vitro.
We hypothesise that rapid, pH-dependent dissolution of ZnONP inside of phagosomes is the main cause of ZnONP-induced diverse progressive severe lung injuries.
We evaluated the performance of the MinION DNA sequencer in-flight on the International Space Station (ISS), and benchmarked its performance off-Earth against the MinION, Illumina MiSeq, and PacBio ...RS II sequencing platforms in terrestrial laboratories. Samples contained equimolar mixtures of genomic DNA from lambda bacteriophage, Escherichia coli (strain K12, MG1655) and Mus musculus (female BALB/c mouse). Nine sequencing runs were performed aboard the ISS over a 6-month period, yielding a total of 276,882 reads with no apparent decrease in performance over time. From sequence data collected aboard the ISS, we constructed directed assemblies of the ~4.6 Mb E. coli genome, ~48.5 kb lambda genome, and a representative M. musculus sequence (the ~16.3 kb mitochondrial genome), at 100%, 100%, and 96.7% consensus pairwise identity, respectively; de novo assembly of the E. coli genome from raw reads yielded a single contig comprising 99.9% of the genome at 98.6% consensus pairwise identity. Simulated real-time analyses of in-flight sequence data using an automated bioinformatic pipeline and laptop-based genomic assembly demonstrated the feasibility of sequencing analysis and microbial identification aboard the ISS. These findings illustrate the potential for sequencing applications including disease diagnosis, environmental monitoring, and elucidating the molecular basis for how organisms respond to spaceflight.
Purpose The purpose of this article is to revisit the role of augmentative and alternative communication (AAC) in poststroke aphasia rehabilitation. The authors' intent is to provide a viewpoint that ...expands the use of AAC in poststroke aphasia rehabilitation. Specifically, we seek to clarify the role of AAC in restorative and participation approaches to aphasia rehabilitation while also considering the role of AAC in a comprehensive treatment plan. The authors support their viewpoint with citations from both the historic and contemporary literature on aphasia rehabilitation. Conclusions A thought-provoking viewpoint on the role of AAC in poststroke aphasia rehabilitation is proposed. More specifically, the versatility of AAC strategies is reviewed, with an emphasis on how AAC can be used to empower people with aphasia to fully participate and engage in life activities with increased independence. Moreover, we argue that AAC can be viewed as a dual-purpose tool that can simultaneously serve to drive intersystemic reorganization resulting in some improved language performance-and perhaps restoration of language function-while offering a communication alternative during inevitable anomic events.
The complex refractive indices of freshly excised healthy breast tissue and breast cancers collected from 20 patients were measured in the range of 0.15 - 2.0 THz using a portable terahertz pulsed ...transmission spectrometer. Histology was performed to classify the tissue samples as healthy adipose tissue, healthy fibrous breast tissue, or breast cancers. The average complex refractive index was determined for each group and it was found that samples containing cancer had a higher refractive index and absorption coefficient. The terahertz properties of the tissues were also used to simulate the impulse response functions expected when imaging breast tissue in a reflection geometry as in terahertz pulsed imaging (TPI). Our results indicate that both TPS and TPI can be used to distinguish between healthy adipose breast tissue, healthy fibrous breast tissue and breast cancer due to the differences in the fundamental optical properties.
Despite the increased emphasis on domestic politics in the study of international law, scholars remain divided about whether and how international law affects domestic institutions. Moreover, while ...public support is a core ingredient for sustainable, legitimate policies in a democracy, research at the individual level of analysis remains limited. Weighing in on these areas of study, we investigate the use of drone strikes for counterterrorism, a subject of considerable debate. Proponents in the government point to drones as both effective for disrupting terrorist networks and compatible with international law. Critics from groups such as international organizations (IOs) and nongovernmental organizations (NGOs) respond that attacks create more terrorists than they kill and violate legal commitments. The central question we ask in this article is whether these international legal criticisms impact public support for drone strikes, the centerpiece of US counterterrorism policy, or whether individuals are more persuaded by effectiveness-based arguments. Employing a survey experiment of a nationally representative sample of the United States, we find IO and NGO criticisms can shape public attitudes even around an important national security issue like drone strikes, but are most influential when messages center on legal critiques rather than matters of effectiveness. Our findings speak to fundamental questions about the domestic politics of international legal commitments, the role of IOs and NGOs in shaping political debates, and the durability of US counterterrorism policy.
A unique property of mitochondria in mammalian cells is their ability to physically interact and undergo dynamic events of fusion/fission that remodel their morphology and possibly their function. In ...cultured cells, metabolic perturbations similar to those incurred during exercise influence mitochondrial fusion and fission processes, but it is unknown whether exercise acutely alters mitochondrial morphology and/or membrane interactions in vivo. To study this question, we subjected mice to a 3-h voluntarily exercise intervention following their normal physical activity patterns, and quantified mitochondrial morphology and membrane interactions in the soleus using a quantitative electron microscopy approach. A single exercise bout effectively decreased blood glucose (P < 0.05) and intramyocellular lipid content (P < 0.01), indicating increased muscle metabolic demand. The number of mitochondria spanning Z-lines and proportion of electron-dense contact sites (EDCS) between adjacent mitochondrial membranes were increased immediately after exercise among both subsarcolemmal (+116%, P < 0.05) and intermyofibrillar mitochondria (+191%, P < 0.001), indicating increased physical interactions. Mitochondrial morphology, and abundance of the mitochondrial pro-fusion proteins Mfn2 and OPA1 were unchanged. Collectively, these results support the notion that mitochondrial membrane dynamics are actively remodelled in skeletal muscle, which may be regulated by contractile activity and the metabolic state. Future studies are required to understand the implications of mitochondrial dynamics in skeletal muscle physiology during exercise and inactivity.
Non-tuberculous mycobacteria (NTM) are ubiquitous environmental organisms that can cause chronic pulmonary infection, particularly in individuals with pre-existing inflammatory lung disease, such as ...cystic fibrosis (CF). Pulmonary disease (PD) caused by NTM has emerged as a major threat to the health of individuals with CF, but remains difficult to diagnose and problematic to treat. In response to this challenge, the US Cystic Fibrosis Foundation (CFF) and the European Cystic Fibrosis Society (ECFS) convened a panel of 19 experts to develop consensus recommendations for the screening, investigation, diagnosis and management of NTM-PD in individuals with CF. PICO (population, intervention, comparison, outcome) methodology and systematic literature reviews were employed to inform draft recommendations, which were then modified to achieve consensus and subsequently circulated for public consultation within the USA and European CF communities. We have thus generated a series of pragmatic, evidence-based recommendations as an initial step in optimising management for this challenging condition.
Text-to-speech (TTS) technology potentially benefits people with aphasia by presenting content through two modalities simultaneously; however, for this to help, eye fixations must synchronize with ...the auditory rendition of words. Researchers have yet to explore how often and to what extent people with aphasia achieve modality synchronization. This retrospective analysis examined the percent of words people with aphasia see and hear concurrently when reading passages presented via TTS technology. Text-to-speech (TTS) technology potentially benefits people with aphasia by presenting content through two modalities simultaneously; however, for this to help, eye fixations must synchronize with the auditory rendition of words. Researchers have yet to explore how often and to what extent people with aphasia achieve modality synchronization. This retrospective analysis examined the percent of words people with aphasia see and hear concurrently when reading passages presented via TTS technology.
Nine adults with aphasia had their eye movements tracked while processing TTS passages at a preselected default rate of 150 words per minute. Modality synchronization occurred whenever fixation on a written word occurred during the time span beginning 300 ms before auditory presentation and ending at the next word's initiation. Correlations between standardized test scores, unsupported reading rate, and modality synchronization percentages were informative about the association of aphasia and reading impairment severity with achievement of synchronicity.
Three participants demonstrated consistent modality synchronization; average synchronicity ranged from 67% to 76% of passage words. One participant displayed inconsistent synchronization within passages and achieved an average of 58%. The remaining five participants rarely achieved synchronization, with fixations typically lagging substantially behind the auditory presentation. A significant positive correlation occurred between paragraph reading comprehension test scores and modality synchronization percentages.
A default TTS presentation rate does not result in dual modality synchronization for most people with aphasia. This lack of synchronization may contribute to inconsistencies in the benefit people with aphasia experience when provided with TTS support.
Non-tuberculous mycobacteria (NTM) are ubiquitous environmental organisms that can cause chronic pulmonary infection, particularly in individuals with pre-existing inflammatory lung disease such as ...cystic fibrosis (CF). Pulmonary disease caused by NTM has emerged as a major threat to the health of individuals with CF but remains difficult to diagnose and problematic to treat. In response to this challenge, the US Cystic Fibrosis Foundation (CFF) and the European Cystic Fibrosis Society (ECFS) convened an expert panel of specialists to develop consensus recommendations for the screening, investigation, diagnosis and management of NTM pulmonary disease in individuals with CF. Nineteen experts were invited to participate in the recommendation development process. Population, Intervention, Comparison, Outcome (PICO) methodology and systematic literature reviews were employed to inform draft recommendations. An anonymous voting process was used by the committee to reach consensus. All committee members were asked to rate each statement on a scale of: 0, completely disagree, to 9, completely agree; with 80% or more of scores between 7 and 9 being considered 'good' agreement. Additionally, the committee solicited feedback from the CF communities in the USA and Europe and considered the feedback in the development of the final recommendation statements. Three rounds of voting were conducted to achieve 80% consensus for each recommendation statement. Through this process, we have generated a series of pragmatic, evidence-based recommendations for the screening, investigation, diagnosis and treatment of NTM infection in individuals with CF as an initial step in optimising management for this challenging condition.
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