Alzheimer's disease (AD) is a neurodegenerative disease that results in severe disability. Very few studies have explored changes in daily physical activity patterns during early stages of AD when ...components of physical function and mobility may be preserved.
Our study explored differences in daily physical activity profiles, independent of the effects of non-cognitive factors including physical function and age, among individuals with mild AD compared to controls.
Patients with mild AD and controls (n = 92) recruited from the University of Kansas Alzheimer's Disease Center Registry, wore the Actigraph GT3X+ for seven days, and provided objective physical function (VO2 max) and mobility data. Using multivariate linear regression, we explored whether individuals with mild AD had different daily average and diurnal physical activity patterns compared to controls independent of non-cognitive factors that may affect physical activity, including physical function and mobility.
We found that mild AD was associated with less moderate-intensity physical activity (p < 0.05), lower peak activity (p < 0.01), and lower physical activity complexity (p < 0.05) particularly during the morning. Mild AD was not associated with greater sedentary activity or less lower-intensity physical activity across the day after adjusting for non-cognitive covariates.
These findings suggest that factors independent of physical capacity and mobility may drive declines in moderate-intensity physical activity, and not lower-intensity or sedentary activity, during the early stage of AD. This underscores the importance of a better mechanistic understanding of how cognitive decline and AD pathology impact physical activity. Findings emphasize the potential value of designing and testing time-of-day specific physical activity interventions targeting individuals in the early stages of AD, prior to significant declines in mobility and physical function.
Summary Background MEK is a member of the MAPK signalling cascade that is commonly activated in melanoma. Direct inhibition of MEK blocks cell proliferation and induces apoptosis. We aimed to analyse ...safety, efficacy, and genotyping data for the oral, small-molecule MEK inhibitor trametinib in patients with melanoma. Methods We undertook a multicentre, phase 1 three-part study (dose escalation, cohort expansion, and pharmacodynamic assessment). The main results of this study are reported elsewhere; here we present data relating to patients with melanoma. We obtained tumour samples to assess BRAF mutational status, and available tissues underwent exploratory genotyping analysis. Disease response was measured by Response Evaluation Criteria in Solid Tumors, and adverse events were defined by common toxicity criteria. This study is registered with ClinicalTrials.gov , number NCT00687622. Findings 97 patients with melanoma were enrolled, including 81 with cutaneous or unknown primary melanoma (36 BRAF mutant, 39 BRAF wild-type, six BRAF status unknown), and 16 with uveal melanoma. The most common treatment-related adverse events were rash or dermatitis acneiform (n=80; 82%) and diarrhoea (44; 45%), most of which were grade 2 or lower. No cutaneous squamous-cell carcinomas were recorded. Of 36 patients with BRAF mutations, 30 had not received a BRAF inhibitor before; two complete responses (both confirmed) and ten partial responses (eight confirmed) were noted in this subgroup (confirmed response rate, 33%). Median progression-free survival of this subgroup was 5·7 months (95% CI 4·0–7·4). Of the six patients who had received previous BRAF inhibition, one unconfirmed partial response was recorded. Of 39 patients with BRAF wild-type melanoma, four partial responses were confirmed (confirmed response rate, 10%). Interpretation Our data show substantial clinical activity of trametinib in melanoma and suggest that MEK is a valid therapeutic target. Differences in response rates according to mutations indicate the importance of mutational analyses in the future. Funding GlaxoSmithKline.
Due to environmental problems by the use of synthetic fibers in composite materials, researchers are more concerned with searching for eco-friendly materials. Consequently, the use of reinforcing ...fibers of natural origin is the best option that promotes the obtaining of materials that do not harm the environment. This paper presents characterization of Cortaderia selloana grass (Pampas) fibers by physical-chemical analysis, FTIR, XRD, thermogravimetric analysis, single fiber tensile test and SEM analysis. Diameter (372.6 µm), density (1261 kg/m
3
), cellulose content (53.7 wt.%), crystallinity index (22%), tensile strength (20 ± 1.0 MPa), Young's modulus (8.88 GPa), and thermal stability (320°C) properties were identified in the Cortaderia selloana grass (Pampas) fibers. Overall properties of these fibers showed that it could be an alternative source as reinforcement material for the manufacture of composite materials.
Respiratory tract viruses are the second most common cause of olfactory dysfunction. As we learn more about the effects of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), with the ...recognition that olfactory dysfunction is a key symptom of this disease process, there is a greater need than ever for evidence-based management of postinfectious olfactory dysfunction (PIOD).
Our aim was to provide an evidence-based practical guide to the management of PIOD (including post–coronavirus 2019 cases) for both primary care practitioners and hospital specialists.
A systematic review of the treatment options available for the management of PIOD was performed. The written systematic review was then circulated among the members of the Clinical Olfactory Working Group for their perusal before roundtable expert discussion of the treatment options. The group also undertook a survey to determine their current clinical practice with regard to treatment of PIOD.
The search resulted in 467 citations, of which 107 articles were fully reviewed and analyzed for eligibility; 40 citations fulfilled the inclusion criteria, 11 of which were randomized controlled trials. In total, 15 of the articles specifically looked at PIOD whereas the other 25 included other etiologies for olfactory dysfunction.
The Clinical Olfactory Working Group members made an overwhelming recommendation for olfactory training; none recommended monocycline antibiotics. The diagnostic role of oral steroids was discussed; some group members were in favor of vitamin A drops. Further research is needed to confirm the place of other therapeutic options.
Objectives/Hypothesis:
The aim of this study was to compare microbiological culture‐based and culture‐independent (16S rRNA gene sequencing) methodologies for pathogen identification in chronic ...rhinosinusitis (CRS) patients. We hypothesized that bacterial culture and DNA sequencing would yield largely concurrent results, although sequencing would detect greater bacterial diversity, and the sinonasal microbiomes of CRS patients would differ in composition and diversity compared with non‐CRS controls.
Study Design:
Cross‐sectional observational study.
Methods:
Middle meatus swabs from CRS patients collected during endoscopic sinus surgery were analyzed by both clinical culture and broad‐range analysis of 16S rRNA gene pyrosequences.
Results:
A total of 21 swab samples from 15 CRS patients and five non‐CRS controls were analyzed. One CRS patient was also swabbed 3 weeks postoperatively due to evidence of purulence during a clinical visit. All subjects had positive bacterial cultures, with a mean of 2.8 isolates per subject. The most prevalent cultivars were coagulase‐negative staphylococci (15/20 specimens, 75%), Staphylococcus aureus (10/20, 50%), and Propionibacterium acnes (6/20, 30%). Among 57,407 pyrosequences generated, the most prevalent were from coagulase‐negative staphylococci (21/21 specimens, 100%), Corynebacterium spp (18/21, 85.7%), P acnes (16/21, 76.2%), and S aureus (14/21, 66.7%). Bacterial diversity correlated with recent antibiotic use, asthma, prior sinus surgery, and relative abundance of S aureus.
Conclusions:
DNA pyrosequencing revealed greater biodiversity than culture, although in most cases culture results represented a subset of the abundant DNA sequence types. CRS patients were characterized by altered microbial composition (P = .02) and greater abundance of S aureus (P = .03).
Awareness of ergonomics is growing into surgical specialties including otolaryngology. Most otolaryngologists experience occupational physical discomfort, and daily incorporation of standard ...ergonomic principles may alleviate some of this pain.
Further demonstration of surgery-related physical discomfort has been documented based on surveys of general otolaryngologists and subspecialty rhinologists. One study utilized surface electromyography to document physical findings directly associated with the endoscopic sinus surgery procedure. However, relatively little work has been published on interventions to relieve task-related pain and body discomfort in rhinology.
Surgeon fatigue and bodily injury is a surprisingly frequent occurrence and is more likely to occur in procedures that are mentally challenging, prolonged, and require the surgeon to operate in a fixed position. Endoscopic sinus and skull base surgeons appear particularly susceptible to task-related physical discomfort, and incorporation of ergonomic principles should be a priority.
The objective of this research work is to study the impact of graphite forms used as solid lubricant additives on brake friction materials performance. Three composites were fabricated using the ...conventional process and were characterised for its physical, chemical, mechanical and thermal properties conforming to industrial standards. The thermal stability of the graphite particles and developed composites was measured in an air atmosphere using the thermogravimetric analyser. The tribological performances were studied using the Chase friction test machine as per IS-2742 Part-4 standard. The results indicated that the friction composite containing expandable graphite exhibited better thermal stability with good fade and recovery performances. This led to enhance wear resistance and stable friction due to its better heat dissipation and lubricity comparing with the other two composites. An empirical relationship for the friction and wear was developed based on Chase test results. The worn surface morphologies of the Chase tested composites were analysed using scanning electron microscopy to study the sensitivity of the friction–wear mechanisms to the graphite-type effect.
Purpose
The purpose of this study is to investigate the influence of commercially available iron–aluminum alloy compared to copper, iron and aluminum powders on the tribological performances of ...friction composites. The main objective is to replace copper from the friction composite formulations.
Design/methodology/approach
In this study, friction composites were fabricated as of standard brake pads using commercially available iron–aluminum alloy and compared to copper powder, iron powder and aluminum powder-based without varying the other ingredients. The brake pads were developed as per the industrial procedure. The physical, mechanical and thermal properties of the developed brake pads were analyzed as per industrial standards. Tribological properties were analyzed using the chase test. Initial speed and deceleration tests in a real-time braking scenario were performed using a full-scale inertia brake dynamometer. Worn surface analysis was done using a scanning electron microscope.
Findings
The results indicate that iron–aluminum alloy (mechanomade)-based friction composites possess good physical, chemical, thermal and mechanical properties with stable fade and recovery characteristics due to its composition and flake morphology. During initial speed and deceleration braking conditions, iron–aluminum alloy also showed good tribological behavior.
Originality/value
This paper explains the influence of commercially available iron–aluminum alloy in friction composites in enhancing tribological performance by its composition and flake morphology, which could potentially replace copper in friction composites by solving subsequent problems.
Purpose:
A wide variety of encryption-based, key-exchange-based, privacy-based, and confidentiality-based models are proposed by researchers, which assist in enhancing security performance under ...real-time attacks. But most of these models are either unsalable due to their QoS (Quality of Service) performance under large loads, or showcase lower attack detection efficiency for heterogeneous attacks.
Methods:
To overcome these issues, this text proposes the design of a novel iterative learning contextual-sidechaining model for improving the security of priority-aware cloud resources. The proposed model initially uses a single-chained blockchain, which is split into multiple sidechains via Grey Wolf Optimization (GWO). These sidechains are reconfigured via a Bacterial Foraging Optimizer (BFO), which assists in deciding encryption and hashing techniques for individual chains. The BFO Model uses a resource-level priority metric, which assists in deciding the level of security and QoS for individual sidechains. The model is further extended by a Particle Swarm Optimizer (PSO) which assists in iteratively optimizing the GWO & BFO Models for QoS & Security enhancements.
Results:
Due to these enhancements, the proposed model is able to improve multiple QoS metrics even under heterogeneous attacks. The proposed model was tested under Sybil, distributed denial of service, masquerading, and spoofing attacks with multiple communication configurations.
Conclusion:
It was observed that the model was able to reduce the delay needed for communication by 8.5 %, improve the energy efficiency by 3.9 %, and increase the throughput by 4.5 %, and improve the request processing performance by 2.5 % under large-scale requests.
OBJECTIVE—Increased vascular permeability is a hallmark of sepsis and acute respiratory distress syndrome. Angiopoietin (Ang2) induces vascular leak, and excess Ang2 generation is associated with ...patient mortality from these diseases. However, mechanisms dampening Ang2 generation during injury remain unclear. Interestingly, microRNA (miR)-150 levels were decreased in septic patients. miR regulate signaling networks by silencing mRNAs containing complementary sequences. Thus, we hypothesized that miR-150 suppresses Ang2 generation and thereby resolves vascular injury.
APPROACH AND RESULTS—Wild-type or miR-150 mice or endothelial cells were exposed to lipopolysaccharide or sepsis, and Ang2 levels, adherens junction reannealing, endothelial barrier function, and mortality were determined. Although Ang2 transiently increased during lipopolysaccharide-induced injury in wild-type endothelial cells and lungs, miR-150 expression was elevated only during recovery from injury. Deletion of miR-150 caused a persistent increase in Ang2 levels and impaired adherens junctions reannealing after injury, resulting thereby in an irreversible increase in vascular permeability. Also, miR-150 mice died rapidly after sepsis. Rescuing miR-150 expression in endothelial cells prevented Ang2 generation, thereby restoring vascular barrier function in miR-150 mice. miR-150 terminated Ang2 generation by targeting the transcription factor, early growth response 2. Thus, early growth response 2 or Ang2 depletion in miR-150 endothelial cells restored junctional reannealing and reinstated barrier function. Importantly, upregulating miR-150 expression by injecting a chemically synthesized miR-150 mimic into wild-type mice vasculature decreased early growth response 2 and Ang2 levels and hence mortality from sepsis.
CONCLUSIONS—miR-150 is a novel suppressor of Ang2 generation with a key role in resolving vascular injury and reducing mortality resulting from sepsis.
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