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Identifying the role of Nox5-induced oxidative stress opens novel avenues for diagnosis and treatment of smoking-induced cardiovascular disease.
In this study we provide evidence that nicotine induces Nox5-mediated pro-calcific processes as novel mechanism of increased atherosclerotic calcification. We identified that activation of α7 and α3 nAChR by nicotine increases intracellular Ca2+ and initiates calcification of hVSMCs through increased Nox5 activity, leading to oxidative stress-mediated EV release. Identifying the role of Nox5-induced oxidative stress opens novel avenues for diagnosis and treatment of smoking-induced cardiovascular disease.
Police are frequently exposed to occupational trauma, making them vulnerable to post-traumatic stress disorder (PTSD) and other mental health conditions. Through personal and occupational trauma police are also at risk of developing Complex PTSD (CPTSD), associated with prolonged and repetitive trauma. Police Occupational Health Services require effective interventions to treat officers experiencing mental health conditions, including CPTSD. However, there is a lack of guidance for the treatment of occupational trauma.
To explore differences in demographics and trauma exposure between police with CPTSD and PTSD and compare the effectiveness of brief trauma-focused therapy between these diagnostic groups.
Observational cohort study using clinical data from the Trauma Support Service, providing brief trauma-focused therapy for PTSD (cognitive behavioural therapy/eye movement desensitization and reprocessing) to UK police officers. Demographics, trauma exposure, baseline symptom severity and treatment effen and relational difficulties) are also reduced.
Peripheral muscle involvement in systemic sclerosis (SSc) may comprise myositis or a non-inflammatory myopathy. There is little understanding on the nature of SSc myopathy. This pilot study aimed to evaluate for the presence of diffuse fibrosis in the peripheral muscle of patients with SSc by determining extracellular volume (ECV) MRI measurement.
SSc patients, with suspected myopathy or no muscle involvement, and healthy volunteers (HV) had native T1 and ECV MRI quantification of the thigh and creatine-kinase (CK) measured. Suspected myopathy was defined as current/history of minimally raised CK (<600 IU/l) +/- presence of clinical signs-symptoms (proximal muscle weakness and/or myalgia) +/- a Manual Muscle Testing score <5 in the thighs.
12 SSc patients and 10 HV were recruited. 9/12 patients had limited cutaneous SSc, 4/12 interstitial lung disease, 7/12 suspected myopathy. p-Hydroxy-cinnamic Acid concentration Higher skeletal muscle ECV was recorded in SSc patients compared to HV [mean (SD) 23(11)%, vs 11(4)% p = 0.04].Peripheral muscle ECV associated with CK (rho=0.554, p = 0.061) and was higher in SSc patients with myopathy compared to those with no myopathy [mean (SD) 28 (10) vs 15 (5), p = 0.023]. An ECV of 22% was determined to best identify myopathy with a sensitivity of 71% and a specificity of 80%.
This hypothesis-generating study showed higher ECV in SSc patients compared to HV as well as association of ECV with suspected myopathy, suggesting the presence of diffuse fibrosis in the peripheral muscle of SSc patients. Further studies are needed to understand the nature of SSc myopathy.
This hypothesis-generating study showed higher ECV in SSc patients compared to HV as well as association of ECV with suspected myopathy, suggesting the presence of diffuse fibrosis in the peripheral muscle of SSc patients. Further studies are needed to understand the nature of SSc myopathy.Intrusive leadership is a method that looks for signs that might indicate a problem within or outside of the workplace that can affect a member's performance and, subsequently, the mission. Our scenario demonstrates how intrusive leadership can identify potential problems which, when coupled with accountability, can prevent more significant complications.
Subjective loss of response immediately prior to routine TNFi therapy can occur in axial spondyloarthritis (axSpA). We investigated clinical outcomes in patients taking the first 3 licenced TNFis and correlated this with recurrence of MRI bone marrow oedema (MRI-BMO).
Proof-of-concept study including axSpA patients established on etanercept (ETA), adalimumab (ADA) or infliximab (IFX) reporting symptom deterioration prior to next dose. MRI/clinical data were collected prior to scheduled dose (v1), 4 days post-dose (v2) and at the time of patient-reported symptom return (v3). MRI spine/sacroiliac joints utilising 3 T were scored using the semi-quantitative Leeds MRI scoring system.
113 clinical assessments and MRIs were performed in 38 participants (ADA = 16, ETA = 12, IFX = 10), mean age 42.1 years ± 24.4(2SD, n = 38), 71.1% male (n = 27/38), 69.7% HLA-B27 positive (n = 23/33). At v1 all patients had high disease activity [ASDAS-CRP = 3 (2.7-3.7)] and 57.9% had MRI-BMO (number of MRI-BMO ETA = 26, ADA = 59, IFX = 28). Improved clinical responses were seen at v2 [ASDAS-CRP -0.41(-0.81-0.30), p= 0.018; BASDAI -0.58(-2.2-0.52), p= 0.024]. Despite just a 4-day interval between v1 and v2, a numerical reduction in MRI-BMO lesions between v1/v2 was observed (ETA=-6, ADA=-10, IFX=-3). By v3 comparatively fewer new BMO lesions were detected in the ETA and ADA groups compared with IFX (ETA=-1, ADA = +3, IFX = +8), although the numbers were too small to enable testing for statistical significance.
Short-lived fluctuations in MRI-BMO were commoner with longer-acting agents and corresponded with subjective loss of clinical response before next scheduled TNFi dose. Larger studies are need to confirm the possible pathogenic implications of this phenomenon.
Short-lived fluctuations in MRI-BMO were commoner with longer-acting agents and corresponded with subjective loss of clinical response before next scheduled TNFi dose. Larger studies are need to confirm the possible pathogenic implications of this phenomenon.
Training combat personnel in combat first-aid skills has faced many challenges over time, such as the need to combine tactics with medicine and to overcome combat personnel's lack of medical background knowledge. Therefore, many simulation methods are currently being developed, each of which has its advantages and disadvantages. In this study, a combined simulation method involving live-actor patients using a wearable training apparatus was developed, and the effects of this method were observed.
Focusing on the major causes of preventable deaths among victims killed in action, wearable training apparatuses simulating massive hemorrhage, airway obstruction, and tension pneumothorax were designed and produced. Methods of simulating these three injury types using live-actor patients with these training apparatuses were developed, and medical teachers evaluated the simulation effects. The live-actor patients were incorporated into a tactical scenario to train and test nonmedical and medical students in year ctical situations with first aid better than high-fidelity simulators. The nonmedical students strongly agreed that live-actor patients were more helpful in the training of injury evaluation than high-fidelity simulators.
The method using wearable training apparatus-based live-actor patients was satisfying and effective for teaching life-saving combat first-aid skills, especially for nonmedical students.
The method using wearable training apparatus-based live-actor patients was satisfying and effective for teaching life-saving combat first-aid skills, especially for nonmedical students.
The TNM classification is the main tool for lymph node (LN) staging in gastric cancer (GC). However, alternative LN staging systems have been proposed, and the role of features other than the number of metastatic LNs is being investigated. Our aim is to discuss the main challenges of LN assessment in GC.
Comprehensive review of the literature on alternative LN staging systems, examined LNs, sentinel LN (SLN) biopsy, LN micrometastases (LNMIs), extracapsular extension (ECE), and tumor deposits (TDs) in GC.
Many controversies exist regarding LN assessment in GC. The TNM classification shows excellent prognostic performance, but alternative prognostic methods such as the LN ratio or log odds of positive LNs have demonstrated to be better than the TNM system in terms of prognostic accuracy. The value of SLN biopsy and LNMIs in GC is still unclear, and several challenges concerning their clinical impact and pathologic analysis must be overcome before their introduction in clinical practice. Most authors have identified ECE and TDs as independent prognostic factors for survival in GC.
Further studies should be performed to evaluate the impact of these features on the TNM classification and patient outcomes, as well as to standardize alternative LN staging systems.
Further studies should be performed to evaluate the impact of these features on the TNM classification and patient outcomes, as well as to standardize alternative LN staging systems.
Limited data about use of biosimilars are available in children with Juvenile Idiopathic Arthritis (JIA). This study therefore aimed to evaluate long-term efficacy and safety of switching from etanercept (ETA) and adalimumab (ADA) originators to their biosimilars, in children with JIA, in a real-world setting.
This is a retro-prospective non-interventional multicentre Italian comparative cohort study. Medical charts of JIA children treated with biosimilars of ETA or ADA were included. Efficacy and safety of TNF-inhibitors therapy was evaluated at last follow-up during originator and at 3, 6 and 12 months following the switch to biosimilar.
59 children (42 female, median age at onset 88 months) were treated with biosimilar of ETA (21) and ADA (38). Forty-five switched from the originator to the BIO (17 ETA, 28 ADA). At time of switch, 12/17 patients on ETA and 18/28 on ADA were in remission. No significant difference has been found at 3, 6 and 12 months after the switch. Ten patients discontinued biosimilars due to disease remission (4 ETA, 3 ADA), family willing (1 ETA), occurrence of burning at injection site (1 ETA), and persistent activity (1 ADA). No statistically significant difference was observed between originator and BIOs, nor between originator and BIOs, and between ADA and ETA in time to disease remission achievement, time to relapse and number of patients who experienced AE.
Our real-life results seem to confirm the efficacy and safety profile of switching from originator of ADA and ETA to their respective BIOs also in paediatric patients with JIA.
Our real-life results seem to confirm the efficacy and safety profile of switching from originator of ADA and ETA to their respective BIOs also in paediatric patients with JIA.
Recent advances in cardiac magnetic resonance imaging (CMR) and other diagnostic techniques have made it easier to identify subclinical cardiac inflammation and dysfunction in the idiopathic inflammatory myopathies (IIM). Herein, we systematically review the literature regarding cardiac involvement in IIM.
We searched Medline and EMBASE from 1990-2020 using keywords related to IIM and cardiac disease. We included English language studies in adults with any immune-mediated, inflammatory muscle pathology.
We identified 10425 potentially relevant abstracts, of which 29 were included. Most frequently these included patients with polymyositis or dermatomyositis without symptomatic myocarditis. Five categories of cardiac investigation were used in these patients cardiac enzyme testing, electrocardiography (ECG), transthoracic echocardiography (TTE), CMR and nuclear medicine testing. Patients with clinical myocarditis had universally abnormal cardiac troponin levels and ECG. Elevated cardiac troponin T was more common than troponin I (cTnI) and may correlate with disease activity, whereas cTnI was more specific for cardiac involvement.