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Idiopathic pulmonary fibrosis (IPF) is a progressive, relentless, and deadly disease. Little is known about its pathogenetic mechanisms; therefore, developing efficient pharmacological therapies is challenging. This work aimed to apply a therapeutic alternative using immunomodulatory peptides in a chronic pulmonary fibrosis murine model. BALB/c mice were intratracheally instilled with bleomycin (BLM) and followed for 30 days. The mice were treated with the immune modulatory peptides ToAP3 and ToAP4 every three days, starting on the 5th day post-BLM instillation. ELISA, qPCR, morphology, and respiratory function analyses were performed. The treatment with both peptides delayed the inflammatory process observed in the non-treated group, which showed a fibrotic process with alterations in the production of collagen I, III, and IV that were associated with significant alterations in their ventilatory mechanics. The ToAP3 and ToAP4 treatments, by lung gene modulation patterns, indicated that distinct mechanisms determine the action of peptides. Both peptides controlled the experimental IPF, maintaining the tissue characteristics and standard function properties and regulating fibrotic-associated cytokine production. Data obtained in this work show that the immune response regulation by ToAP3 and ToAP4 can control the alterations that cause the fibrotic process after BLM instillation, making both peptides potential therapeutic alternatives and/or adjuvants for IPF.

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BACKGROUND: The COVID-19 pandemic put healthcare professionals, including residents (postgraduate trainees of health professions), under intense physical and psychological stress, hence at risk for mental disorders. We evaluated the prevalence of mental disorders among healthcare residents during the pandemic. METHODS: From July to September 2020, residents in medicine and other healthcare specialties in Brazil were recruited. The participants completed electronic forms with validated questionnaires (DASS-21, PHQ-9, BRCS) to screen for depression, anxiety, and stress, and to evaluate resilience. Data on potential predisposing factors for mental disorders were also collected. Descriptive statistics, chi-squared, students t, correlation and logistic regression models were applied. The study received ethical approval, and all participants provided informed consent. RESULTS: We included 1313 participants (51.3% medical; 48.7% nonmedical) from 135 Brazilian hospitals; mean (SD) age: 27.8 (4.4) years; 78.2% females; 59.3% white race. Of all participants, 51.3%, 53.4% and 52.6% presented symptoms consistent with depression, anxiety, and stress, respectively; 61.9% showed low resilience. Nonmedical residents exhibited higher anxiety compared to medical residents (DASS-21 anxiety score, mean difference: 2.26; 95% CI: 1.15-3.37; p < 0.001). In multivariate analyses, having any pre-existent, nonpsychiatric chronic disease was associated with higher prevalence of symptoms indicative of depression (odds ratio, OR: 2.05; 95% CI: 1.47-2.85, on DASS-21 | OR: 2.26; 95% CI: 1.59-3.20, on PHQ-9), anxiety (OR: 2.07; 95% CI: 1.51-2.83, on DASS-21), and stress (OR: 1.53; 95% CI: 1.12-2.09, on DASS-21); other predisposing factors were identified; by contrast, high resilience (BRCS score) was protective against symptoms of depression (OR 0.82; 95% CI: 0.79-0.85, on DASS-21 | OR 0.85; 95% CI: 0.82-0.88, on PHQ-9), anxiety (OR 0.90; 95% CI: 0.87-0.93, on DASS-21), and stress (OR 0.88; 95% CI: 0.85-0.91, on DASS-21); p < 0.05 for all outcomes. CONCLUSIONS: We found a high prevalence of mental disorder symptoms among healthcare residents during COVID-19 pandemic in Brazil. Nonmedical residents exhibited higher levels of anxiety than medical ones. Some predisposing factors for depression, anxiety and stress among residents were identified.

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BACKGROUND: Since the beginning of the COVID-19 pandemic, health professionals have been working under extreme conditions, increasing the risk of physical and mental illness. We evaluated the prevalence of burnout and its associated factors among postgraduate student residents in health professions during the global health crisis. METHODS: Healthcare residents were recruited from all across Brazil between July and September 2020 through digital forms containing instruments for assessing burnout (Oldenburg Burnout Inventory (OLBI)), resilience (brief resilient coping scale (BRCS)) and anxiety, stress and depression (depression, anxiety and stress scale (DASS-21) and Patient Health Questionnaire (PHQ-9)). Additionally, the relationships between burnout and chronic diseases, autonomy and educational adequacy in the residency programme, personal protective equipment (PPE), workload and care for patients with COVID-19 were evaluated. The chi-square test, Student's t test, Pearson's correlation test and logistic regression were performed. RESULTS: A total of 1,313 participants were included: mean (standard deviation) age, 27.8 (4.4) years; female gender, 78.1%; white race, 59.3%; and physicians, 51.3%. The overall prevalence of burnout was 33.4%. The odds (odds ratio [95% confidence interval]) of burnout were higher in the presence of pre-existing diseases (1.76 [1.26-2.47]) and weekly work > 60 h (1.36 [1.03-1.79]) and were lower in the presence of high resilience (0.84 [0.81-0.88]), autonomy (0.87 [0.81-0.93]), and educational structure (0.77 [0.73-0.82]), adequate availability of PPE (0.72 [0.63-0.83]) and non-white race (0.63 [0.47-0.83]). Burnout was correlated with anxiety (r = 0.47; p < 0.05), stress (r: 0.58; p < 0.05) and depression (r: 0.65; p < 0.05). CONCLUSIONS: We observed a high prevalence of burnout among residents during the COVID-19 pandemic. Individual characteristics and conditions related to the work environment were associated with a higher or lower occurrence of the syndrome.

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AIM: Physical exercise training attenuates pulmonary inflammation, but its effects on impaired respiratory function caused by hepatopulmonary syndrome (HPS) have not been evaluated. We determined if the combination of moderate intensity aerobic and resistance training during HPS development modifies exercise capacity, respiratory system mechanics, and lung inflammation responses. MAIN METHODS: Wistar rats were randomly divided into sham, HPS, and HPS + combined exercise training groups. Fifteen days after HPS induction, a moderate intensity aerobic plus resistance exercise training protocol was performed five times a week for 5 weeks on alternate days. Exercise capacity, respiratory system mechanics, lung inflammation, pulmonary morphology, and immunohistochemistry were evaluated. KEY FINDINGS: Overall, our findings indicated that combined exercise training efficiently increased the maximal running and resistance capacity of HPS animals. The training regimen reduced the expression of P2X7 in parenchymal leukocytes (P < 0.01), partially restored the expression of interleukin-10 in airway epithelium (P < 0.01), and increased the expression of TFPI in the airway epithelium (P < 0.01) as well as reduced its expression in parenchymal leukocytes (P < 0.01). However, exercise training did not attenuate HPS-induced respiratory mechanical derangements or lung tissue remodeling. SIGNIFICANCE: Combined exercise training can elicit adaptation with regard to both maximal running capacity and maximum strength and modify the expression of P2X7 and TFPI in parenchymal leukocytes and that of IL-10 in airway epithelium.

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BACKGROUND: Little is known about right ventricular dysfunction in non-advanced idiopathic pulmonary fibrosis (IPF) patients without hypoxemia at rest. We evaluated it at rest and during exercise. RESEARCH DESIGN AND METHODS: 123 IPF patients were evaluated, and 27 met all the following criteria: Gender-Age-Physiology Index score ≤5, modified Medical Research Council dyspnea score ≤3, peripheral oxygen saturation ≥92% at rest, and no history of oxygen therapy. They were submitted to two-dimensional speckle-tracking echocardiography at rest and during cardiopulmonary exercise to analyze right ventricular global longitudinal strain. RESULTS: Abnormal speckle-tracking echocardiography findings were identified in 10/27 patients (37%), indicating right ventricular (RV) dysfunction. No patients had abnormalities observed in conventional echocardiographic parameters. Significant differences in mPAP were observed between patients with RV dysfunction and those without dysfunction (at rest: 26.0 ± 4.8 vs. 19.1 ± 4.2 mmHg, p = 0.001; during exercise: 51.3 ± 6.4 vs. 36.9 ± 14.7 mmHg, p = 0.002). CONCLUSIONS: RV dysfunction was detected in 37% of non-advanced IPF patients and early recognition was only possible using speckle-tracking echocardiography. Special attention should be given to these patients as RV dysfunction is suggestive of worse prognosis. These patients could benefit from new specific drugs or even oxygen therapy for transitory hypoxia.

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OBJECTIVE: To investigate the accuracy of chest auscultation in detecting abnormal respiratory mechanics. METHODS: We evaluated 200 mechanically ventilated patients in the immediate postoperative period after cardiac surgery. We assessed respiratory system mechanics - static compliance of the respiratory system (Cst,rs) and respiratory system resistance (R,rs) - after which two independent examiners, blinded to the respiratory system mechanics data, performed chest auscultation. RESULTS: Neither decreased/abolished breath sounds nor crackles were associated with decreased Cst,rs (≤ 60 mL/cmH2O), regardless of the examiner. The overall accuracy of chest auscultation was 34.0% and 42.0% for examiners A and B, respectively. The sensitivity and specificity of chest auscultation for detecting decreased/abolished breath sounds or crackles were 25.1% and 68.3%, respectively, for examiner A, versus 36.4% and 63.4%, respectively, for examiner B. Based on the judgments made by examiner A, there was a weak association between increased R,rs (≥ 15 cmH2O/L/s) and rhonchi or wheezing (ϕ = 0.31, p < 0.01). The overall accuracy for detecting rhonchi or wheezing was 89.5% and 85.0% for examiners A and B, respectively. The sensitivity and specificity for detecting rhonchi or wheezing were 30.0% and 96.1%, respectively, for examiner A, versus 10.0% and 93.3%, respectively, for examiner B. CONCLUSIONS: Chest auscultation does not appear to be an accurate diagnostic method for detecting abnormal respiratory mechanics in mechanically ventilated patients in the immediate postoperative period after cardiac surgery.

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Introduction: Acute spinal cord injury is associated with an increased risk of thromboembolic events. Low-molecular-weight heparins are first-line medications for both the treatment and prevention of venous thromboembolism. Pharmacological prophylaxis may be indicated for high-risk patients and low-risk patients may be managed with non-pharmacological measures. Case presentation: We report two cases of gluteal hematomas that occurred in patients with chronic spinal cord injury who were under prophylactic doses of enoxaparin at a tertiary rehabilitation hospital. There was no local trauma. The patients needed multiple surgical interventions and rehabilitation treatment was delayed. Discussion: There is a lack of evidence to correctly estimate the thromboembolic risk in chronic spinal cord injury and the duration of prophylaxis. Over-prescription of pharmacological prophylaxis may expose patients to unnecessary risks. These patients frequently present with polypharmacy and reducing the amount of prescribed medication may begin with reducing prophylactic treatments for venous thromboembolism, which may be an overtreatment based on risk overestimation.

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STUDY DESIGN: Retrospective cohort study. OBJECTIVE: To compare the cost and incidence of venous thromboembolism (VTE) and bleeding between two different VTE pharmacological prophylaxis strategies in individuals with spinal cord injury: one based on motor impairment (Protocol 1) and the other based on time from the lesion and presence of associated risk factors for VTE (Protocol 2). SETTING: A tertiary rehabilitation hospital in Brazil. METHODS: We retrospectively reviewed a total of 1475 charts of individual admissions: 814 individuals received pharmacological prophylaxis according to Protocol 1 and 661 according to protocol 2. These cohorts were compared with respect to age, time and level of injury, length of stay, AIS classification, type of injury, and occurrence of VTE and major bleeding. The number of prescribed doses of enoxaparin and expenditures associated with enoxaparin during each period were evaluated. RESULTS: The median lesion time was 3 years. The risk-based strategy drastically reduced the average monthly use of enoxaparin by 75% and the 12-month enoxaparin expenditure by $119,930.33, without increasing the risk of VTE. The incidence density of thromboembolic events was 0.55/10,000 patient-days, and all events occurred in individuals receiving prophylaxis according to Protocol 1. CONCLUSIONS: Time from injury and risk of VTE-based protocol for indication of pharmacological prophylaxis drastically reduced costs. No difference in occurrence of VTE was observed.

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