Bronchial thermoplasty (BT) is a bronchoscopic treatment for severe asthma targeting airway smooth muscle (ASM). Observational studies have shown ASM mass reduction after BT, but appropriate control ...groups are lacking. Furthermore, as treatment response is variable, identifying optimal candidates for BT treatment is important.
First, to assess the effect of BT on ASM mass, and second, to identify patient characteristics that correlate with BT response.
Patients with severe asthma (
= 40) were randomized to immediate (
= 20) or delayed (
= 20) BT treatment. Before randomization, clinical, functional, blood, and airway biopsy data were collected. In the delayed control group, reassessment, including biopsies, was performed after 6 months of standard clinical care, followed by BT. In both groups, post-BT data including biopsies were obtained after 6 months. ASM mass (% positive desmin or α-smooth muscle actin area in the total biopsy) was calculated with automated digital analysis software. Associations between baseline characteristics and Asthma Control Questionnaire and Asthma Quality of Life Questionnaire (AQLQ) improvement were explored.
Median ASM mass decreased by >50% in the immediate BT group (
= 17) versus no change in the delayed control group (
= 19) (
= 0.0004). In the immediate group, Asthma Control Questionnaire scores improved with -0.79 (interquartile range IQR, -1.61 to 0.02) compared with 0.09 (IQR, -0.25 to 1.17) in the delayed group (
= 0.006). AQLQ scores improved with 0.83 (IQR, -0.15 to 1.69) versus -0.02 (IQR, -0.77 to 0.75) (
= 0.04). Treatment response in the total group (
= 35) was positively associated with serum IgE and eosinophils but not with baseline ASM mass.
ASM mass significantly decreases after BT when compared with a randomized non-BT-treated control group. Treatment response was associated with serum IgE and eosinophil levels but not with ASM mass.
Extensive evidence has indicated that a high rate of cholesterol biogenesis and abnormal neuronal energy metabolism play key roles in Alzheimer's disease (AD) pathogenesis. Here, for we believe the ...first time, we used osmotin, a plant protein homolog of mammalian adiponectin, to determine its therapeutic efficacy in different AD models. Our results reveal that osmotin treatment modulated adiponectin receptor 1 (AdipoR1), significantly induced AMP-activated protein kinase (AMPK)/Sirtuin 1 (SIRT1) activation and reduced SREBP2 (sterol regulatory element-binding protein 2) expression in both in vitro and in vivo AD models and in Adipo
mice. Via the AdipoR1/AMPK/SIRT1/SREBP2 signaling pathway, osmotin significantly diminished amyloidogenic Aβ production, abundance and aggregation, accompanied by improved pre- and post-synaptic dysfunction, cognitive impairment, memory deficits and, most importantly, reversed the suppression of long-term potentiation in AD mice. Interestingly, AdipoR1, AMPK and SIRT1 silencing not only abolished osmotin capability but also further enhanced AD pathology by increasing SREBP2, amyloid precursor protein (APP) and β-secretase (BACE1) expression and the levels of toxic Aβ production. However, the opposite was true for SREBP2 when silenced using small interfering RNA in APPswe/ind-transfected SH-SY5Y cells. Similarly, osmotin treatment also enhanced the non-amyloidogenic pathway by activating the α-secretase gene that is, ADAM10, in an AMPK/SIRT1-dependent manner. These results suggest that osmotin or osmotin-based therapeutic agents might be potential candidates for AD treatment.
Cardiovascular diseases (CVDs) increase mortality risk from coronavirus infection (COVID-19). There are also concerns that the pandemic has affected supply and demand of acute cardiovascular care. We ...estimated excess mortality in specific CVDs, both 'direct', through infection, and 'indirect', through changes in healthcare.
We used (i) national mortality data for England and Wales to investigate trends in non-COVID-19 and CVD excess deaths; (ii) routine data from hospitals in England (n = 2), Italy (n = 1), and China (n = 5) to assess indirect pandemic effects on referral, diagnosis, and treatment services for CVD; and (iii) population-based electronic health records from 3 862 012 individuals in England to investigate pre- and post-COVID-19 mortality for people with incident and prevalent CVD. We incorporated pre-COVID-19 risk (by age, sex, and comorbidities), estimated population COVID-19 prevalence, and estimated relative risk (RR) of mortality in those with CVD and COVID-19 compared with CVD and non-infected (RR: 1.2, 1.5, 2.0, and 3.0).Mortality data suggest indirect effects on CVD will be delayed rather than contemporaneous (peak RR 1.14). CVD service activity decreased by 60-100% compared with pre-pandemic levels in eight hospitals across China, Italy, and England. In China, activity remained below pre-COVID-19 levels for 2-3 months even after easing lockdown and is still reduced in Italy and England. For total CVD (incident and prevalent), at 10% COVID-19 prevalence, we estimated direct impact of 31 205 and 62 410 excess deaths in England (RR 1.5 and 2.0, respectively), and indirect effect of 49 932 to 99 865 deaths.
Supply and demand for CVD services have dramatically reduced across countries with potential for substantial, but avoidable, excess mortality during and after the pandemic.
The aim of this study to analyze the effects of the stacking sequence of kenaf and jute fibers on the tensile and flexural properties of the kenaf/jute hybrid composites. Kenaf/jute/kenaf (K/J/K), ...jute/kenaf/jute (J/K/J) and neat epoxy (EP) composites were prepared using the hand lay-up technique while maintaining total fiber loading of 30 wt%. Mechanical properties were analyzed by using Instron Universal Testing machines. The obtained results showed that the K/J/K hybrid composites exhibited the highest tensile strength (43.21 MPa) and flexural strength (75.57 MPa) as compared with J/K/J hybrid composites. K/J/K hybrid composites also display better tensile and flexural modulus of 3.60 GPa and 4.63 GPa, respectively, as compared to J/K/J hybrid and neat epoxy composites. The morphological properties of tensile and flexural fracture samples of the hybrid composites were analyzed by using scanning electron microscopy (SEM). It's clear from SEM that fiber pull-out, and matrix cracks occurs in all composites, but K/J/K hybrid composites display better fiber/matrix interfacial bonding. We concluded from this work that layering sequence plays an important role in the mechanical performance of hybrid composites and attributed that fabricated hybrid composites can be used in engineering application such as interiors for aircrafts and automotive.
In the present study, a shape memory epoxy polymer (SMEP) system was prepared from commercially available EPON 826 and NGDE, and then, 0.5%, 1.0% and 1.5% mass percentage of multi-walled carbon ...nanotubes (MWCNTs) were incorporated into it so as to prepare nanocomposites. The inclusion of the nanofiller into the SMEP system was expected to enhance its properties. Then, experimental analyses were conducted to study the effect of incorporating different amounts of MWCNTs on the thermal properties of the obtained nanocomposites, namely dynamic mechanical analysis, thermogravimetric analysis (TGA) and shape memory cyclic testing. It was found that the increasing content of MWCNTs in the SMEP system decreased the glass transition temperature of the developed nanocomposites (SMEPCs). TGA results indicated that the incorporation of MWCNTs into the SMEP decreased its thermal stability. The authors explained these results by the lack of interaction between the MWCNTs and the epoxy matrix. In consideration of the use of the SMEP for morphing applications, the increment in MWCNT content was found to improve the shape recovery properties of the SMEP. Thus, the study demonstrates that the incorporation of a MWCNT nanofiller can help enhance the properties of the SMEP system and overcome its limitations, revealing the high potential of the developed shape memory composite materials to be used for various industrial applications.
The mechanism of action of bronchial thermoplasty (BT) treatment for patients with severe asthma is incompletely understood. This study investigated the 2.5-year impact of BT on airway smooth muscle ...(ASM) mass and clinical parameters by paired data analysis in 22 patients. Our findings demonstrate the persistence of ASM mass reduction of >50% after 2.5 years. Furthermore, sustained improvement in asthma control, quality of life and exacerbation rates was found, which is in line with previous reports. An association was found between the remaining ASM and both the exacerbation rate (r=0.61, p=0.04 for desmin, r=0.85, p<0.01 for alpha smooth muscle actin (SMA)) and post-bronchodilator forced expiratory volume in 1 s predicted percentage (r=-0.69, p=0.03 for desmin, r=-0.58, p=0.08 for alpha SMA). This study provides new insight into the long-term impact of BT.
Summary
We compared the intubating characteristics of the Pentax Airway Scope, the C‐MAC™ and the Glidescope® with those of the Macintosh laryngoscope in 400 patients without predictors of difficult ...intubation. We found shorter intubation times with the Airway Scope (mean (SD) 20.6 (11.5) s) compared with the C‐MAC (31.9 (17.6) s) and Glidescope (31.2 (15.0) s), p < 0.001. The median (IQR range) score for ease of intubation was significantly lower (better) with the Airway Scope (0 (0–8.75 0–60)) than with the C‐MAC (10 (0–20 0–90)) or Glidescope (0 (0–20 0–80)), p < 0.001. Ease of blade insertion in the C‐MAC (0 (0–0 0–30)) was superior to that of the Airway Scope (0 (0–0 0–70)), Macintosh (0 (0–0 0–80)) or Glidescope (0 (0–10 0–60)), p = 0.006. More patients had a grade 1 laryngeal view with the Airway Scope (97%) compared with the C‐MAC (87%), Glidescope (78%), or Macintosh (58%), p < 0.001. There were no grade 3 laryngeal views with the Airway Scope. The three videolaryngoscopes had comparable first attempt successful intubation rates: 95% for the Airway Scope, 93% for the C‐MAC and 91% for the Glidescope.
Bronchial thermoplasty (BT) is a bronchoscopic procedure in which controlled thermal energy is applied to the airway wall to decrease smooth muscle.
To evaluate the effectiveness and safety of BT ...versus a sham procedure in subjects with severe asthma who remain symptomatic despite treatment with high-dose inhaled corticosteroids and long-acting beta(2)-agonists.
A total of 288 adult subjects (Intent-to-Treat ITT) randomized to BT or sham control underwent three bronchoscopy procedures. Primary outcome was the difference in Asthma Quality of Life Questionnaire (AQLQ) scores from baseline to average of 6, 9, and 12 months (integrated AQLQ). Adverse events and health care use were collected to assess safety. Statistical design and analysis of the primary endpoint was Bayesian. Target posterior probability of superiority (PPS) of BT over sham was 95%, except for the primary endpoint (96.4%).
The improvement from baseline in the integrated AQLQ score was superior in the BT group compared with sham (BT, 1.35 +/- 1.10; sham, 1.16 +/- 1.23 PPS, 96.0% ITT and 97.9% per protocol). Seventy-nine percent of BT and 64% of sham subjects achieved changes in AQLQ of 0.5 or greater (PPS, 99.6%). Six percent more BT subjects were hospitalized in the treatment period (up to 6 wk after BT). In the posttreatment period (6-52 wk after BT), the BT group experienced fewer severe exacerbations, emergency department (ED) visits, and days missed from work/school compared with the sham group (PPS, 95.5, 99.9, and 99.3%, respectively).
BT in subjects with severe asthma improves asthma-specific quality of life with a reduction in severe exacerbations and healthcare use in the posttreatment period. Clinical trial registered with www.clinialtrials.gov (NCT00231114).
Hematopoietic stem cell transplant (HCT) recipients have a substantial risk of developing secondary solid cancers, particularly beyond 5 years after HCT and without reaching a plateau overtime. A ...working group was established through the Center for International Blood and Marrow Transplant Research and the European Group for Blood and Marrow Transplantation with the goal to facilitate implementation of cancer screening appropriate to HCT recipients. The working group reviewed guidelines and methods for cancer screening applicable to the general population and reviewed the incidence and risk factors for secondary cancers after HCT. A consensus approach was used to establish recommendations for individual secondary cancers. The most common sites include oral cavity, skin, breast and thyroid. Risks of cancers are increased after HCT compared with the general population in skin, thyroid, oral cavity, esophagus, liver, nervous system, bone and connective tissues. Myeloablative TBI, young age at HCT, chronic GVHD and prolonged immunosuppressive treatment beyond 24 months were well-documented risk factors for many types of secondary cancers. All HCT recipients should be advised of the risks of secondary cancers annually and encouraged to undergo recommended screening based on their predisposition. Here we propose guidelines to help clinicians in providing screening and preventive care for secondary cancers among HCT recipients.
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