Hensleymcgowan3237
Current medicine for Alzheimer's disease (AD) cannot effectively reverse or block nerve injury. Traditional Chinese Medicine practice and research imply
(Fuzi) may meet this goal.
Analysing the anti-AD effect of Fuzi and its potential molecular mechanism.
AD model cells were treated with Fuzi in 0-300 mg/mL for 24 h in 37 °C. Inflammation inhibitor The cell viability (CV) and length of cell projections (LCP) for each group were observed, analysed, and standardised using control as a baseline (CV
and LCP
). The Fuzi and AD relevant genes were identified basing on databases, and the molecular mechanism of Fuzi anti-AD was predicted by network analysis.
Experiment results showed that Fuzi in 0.4 mg/mL boosted LCP (LCP
= 1.2533,
≤ 0.05), and in 1.6-100 mg/mL increased CV (CV
from 1.1673 to 1.3321,
≤ 0.05). Bioinformatics analysis found 17 Fuzi target genes (relevant scores ≥ 20), showing strong AD relevant signals (RMS_
≤ 0.05, related scores ≥ 5), enriched in the pathways regulating axon growth, synaptic plasticity, cell survival, proliferation, apoptosis, and death (
≤ 0.05). Especially,
and
interacted with
protein and located in the key point of the "Alzheimer's disease" pathway.
These results suggest that Fuzi may have therapeutic and prevention potential in AD, and
and
may be the core of the pathways of the Fuzi anti-AD process. Fuzi should be studied more extensively, especially for the prevention of AD.
These results suggest that Fuzi may have therapeutic and prevention potential in AD, and GRIN1 and MAPK1 may be the core of the pathways of the Fuzi anti-AD process. Fuzi should be studied more extensively, especially for the prevention of AD.
To evaluate feasibility of scaling up a 12-week community-based exercise program (
) in which young people with disability exercise with a student mentor.
Within a stepped wedge cluster randomised trial, seven domains of feasibility were assessed demand, implementation, acceptability, practicality, adaptation, integration, and expansion.
Of the 163 participants with disability (61 females; 20.8 ± 5 y) and 226 mentors who enrolled, 123 participants and mentors completed
. Population demand was estimated at 9% of members of participating organisations. Most participants (76%) completed the twice-weekly program within 12 weeks, attending 79% of sessions (mean 18.9 ± 4.7). Key program elements valued by participants were the mentor, tailored exercise, and regular program schedule. Majority (87%) of mentors were recruited from physiotherapy, occupational therapy, and exercise science courses. Positives for participants were perceived benefits and organisational support, and for mentors, understanding disaics between the young person, their family/carers and peer mentors are important factors to manage for the successful implementation of FitSkills.
Mortality in Acute Respiratory Distress Syndrome (ARDS) has decreased after the adoption of lung-protective strategies. Lower tidal-volumes, lower driving pressures, lower respiratory rates, and higher end-expiratory pressures have all been suggested as key components of lung protection strategies. A unifying theoretical explanation has been proposed that attributes lung injury to the energy transfer rate (mechanical power) from ventilator to the patient, calculated from a combination of several ventilator variables.
We aimed to assess the impact of mechanical power on mortality in patients with ARDS as compared to that of primary ventilator variables such as driving pressure, tidal volume, and respiratory rate.
We obtained data on ventilatory variables and mechanical power from a pooled database of ARDS patients who had participated in six randomized clinical trials of protective mechanical ventilation, and one large observational cohort of ARDS patients. The primary outcome was mortality at 28 or 60 days.
We included 4,549 patients (38% women; mean age, 55±23 years). Average mechanical power was 0.32±0.14 J.min-1.Kg-1 predicted body weight, driving pressure was 15.0±5.8 cmH2O, and respiratory rate was 25.7±7.4 breaths/minute. link2 Driving pressure, respiratory rate, and mechanical power were significant predictors of mortality in adjusted analyses. The impact of driving pressure on mortality was four times as large as that of respiratory rate.
Mechanical power was associated with mortality during controlled mechanical ventilation in ARDS but a simpler model using only driving pressure and respiratory rate was equivalent.
Mechanical power was associated with mortality during controlled mechanical ventilation in ARDS but a simpler model using only driving pressure and respiratory rate was equivalent.Atypical hemolytic uremic syndrome (aHUS) is a rare disease caused by overactivation of the complement alternative pathway. aHUS involves the presence of antibodies against complement factor H and its mutations in the complement genes. A 2-month-old boy presented with discoid rash, hemolytic anemia, thrombocytopenia, multiple antibodies, and hypocomplementemia with a very low level of C4 ( less then 3 mg/dL), indicating activation of the complement pathway, together fulfilling the systemic lupus erythematosus (SLE) criteria of the American College of Rheumatology at 5 months of age. link3 However, most of these findings normalized spontaneously without any intervention. Further investigations revealed a high level of anti-complement factor H antibodies and a novel heterozygous missense mutation (p.Glu1172Ala, located in exon 22) in a complement gene, CFH. At 2 years of age, his SLE-like symptoms have not recurred, but hematuria and schistocytes were persistent. Eventually, aHUS was diagnosed rather than SLE. Our findings suggest that multiple antibody complex, including anti-complement factor H antibody, may temporarily activate the classical pathway, resulting in SLE-like findings.Bronchopulmonary dysplasia (BPD), the most common sequela of preterm birth, is a severe disorder of the lung that is often associated with long-lasting morbidity. A hallmark of BPD is the disruption of alveolarization whose pathogenesis is incompletely understood. Here, we tested the vascular hypothesis that disordered vascular development precedes the decreased alveolarization associated with BPD. Neonatal mouse pups were exposed to 7, 14 or 21 days of normoxia (21% O2) or hyperoxia (85% O2) with n=8-11 for each group. The right lungs were fixed by vascular perfusion and investigated by design-based stereology or three-dimensional (3D) reconstruction of data sets obtained by serial block-face scanning electron microscopy. The alveolar capillary network of hyperoxia-exposed mice was characterized by rarefaction, partially altered geometry and widening of capillary segments as shown by 3D reconstruction. Stereology revealed that the development of alveolar epithelium and capillary endothelium was decreased in hyperoxia-exposed mice, however, the time course of these effects was different. That the surface area of the alveolar epithelium was smaller in hyperoxia-exposed mice first became evident at day 14.In contrast, the surface area of the endothelium was reduced in hyperoxia-exposed mouse pups at day 7. The thickness of the air-blood barrier decreased during postnatal development in normoxic mice whereas it increased in hyperoxic mice. The endothelium and the septal connective tissue made appreciable contributions to the thickened septa. In conclusion, the present study provides clear support for the idea that the stunted alveolarization follows the disordered microvascular development, thus supporting the vascular hypothesis of BPD.Although several obesity clinical practice guidelines are available and relevant for primary care, a practical and effective medical model for treating obesity is necessary. The aim of this study was to develop and implement a holistic population health-based framework with components to support primary care-based obesity management in US health care organizations. The Obesity Care Model Collaborative (OCMC) was conducted with guidance and expertise of an advisory committee, which selected participating health care organizations based on prespecified criteria. A committee comprising obesity and quality improvement specialists and representatives from each organization developed and refined the obesity care framework for testing and implementing guideline-based practical interventions targeting obesity. These interventions were tracked over time, from an established baseline to 18 months post implementation. Ten geographically diverse organizations, treating patients with diverse demographics, insurance coverage, and health status, participated in the collaborative. The key interventions identified for managing obesity in primary care were applicable across the 4 OCMC framework domains community, health care organization, care team, and patient/family. Care model components were developed within each domain to guide the primary care of obesity based on each organization's structure, resources, and culture. Key interventions included development of quality monitoring systems, training of leadership and staff, identifying clinical champions, patient education, electronic health record best practice alerts, and establishment of community partnerships, including the identification of external resources. This article describes the interventions developed based on the framework, with a focus on implementation of the model and lessons learned.COVID -19 is an acute infectious disease caused by the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). Human surfactant protein D (SP-D) is known to interact with spike protein of SARS-CoV, but its immune-surveillance against SARS-CoV-2 is not known. The study aimed to examine the potential of a recombinant fragment of human SP-D (rfhSP-D) as an inhibitor of replication and infection of SARS-CoV-2. The interaction of rfhSP-D with spike protein of SARS-CoV-2 and hACE-2 receptor was predicted via docking analysis. The inhibition of interaction between spike protein and ACE-2 by rfhSP-D was confirmed using direct and indirect ELISA. The effect of rfhSP-D on replication and infectivity of SARS-CoV-2 from clinical samples was studied by measuring the expression of RdRp gene of the virus using qPCR. In-silico interaction studies indicated that three amino acid residues in the RBD of spike of SARS-CoV-2 were commonly involved in interacting with rfhSP-D and ACE-2. Studies using clinical samples of SARS-CoV-2 positive cases (asymptomatic, n=7 and symptomatic, n=8 and negative controls n=15) demonstrated that treatment with 1.67 µM rfhSP-D inhibited viral replication by ~5.5 fold and was more efficient than Remdesivir (100 µM). Approximately, a 2-fold reduction in viral infectivity was also observed after treatment with 1.67 µM rfhSP-D. These results conclusively demonstrate that the calcium independent rfhSP-D mediated inhibition of binding between the receptor binding domain of the S1 subunit of the SARS-CoV-2 spike protein and human ACE-2, its host cell receptor, and a significant reduction in SARS-CoV-2 infection and replication in-vitro. This article is open access and distributed under the terms of the Creative Commons Attribution Non-Commercial No Derivatives License 4.0 (http//creativecommons.org/licenses/by-nc-nd/4.0/).
