Impact of Transcranial Direct Current Stimulation in Pain, Fatigue, and Health Quality of Life of Patients with Idiopathic Inflammatory Myopathies: A Randomized, Double-Blind, Sham-Controlled Crossover Clinical Trial.

Objectives: To assess the effectiveness of transcranial direct current stimulation (tDCS) for pain, fatigue, physical function, and health-related quality of life in patients with idiopathic inflammatory myopathy (IIM). Methods: This randomized, double-blind, sham-controlled, crossover clinical trial enrolled IIM patients with fatigue and pain who received tDCS (20 min, 2 mA) or sham stimulation for 10 daily sessions. Electrodes were placed according to the 10/20 EEG system. Both the groups underwent aerobic exercise training during the intervention period. The patients were evaluated for disease perception, pain, and fatigue using uni-multidimensional questionnaires and physical tests in the periods before and after the first and second interventions and after 12 weeks of follow-up. Results: After the tDCS intervention, a reduction in the general score of multidimensional pain of 32.0 (1.5-38.0) vs. 0.0 (0.0-13.4) with effect size (ES) of -0.78 was noted, and after sham intervention, a reduction of 26.0 (0.0-37.0) vs. 5.0 (0.0-19.2) with ES of -0.54 (P = 0.047) was also noted. Similar results were evidenced with fatigue (22.5 (15.4-33.2) vs. 5.5 (0.0-14.6) with ES of -0.82) and sham intervention (21.0 (15.8-29.5) vs. 4.0 (4.0-17.5) with ES of -0.80 (P = 0.012)). There were no differences in the domains of the fatigue and pain questionnaires. Adherence was observed in 88.8% of the patients without adverse events. Conclusion: The association of tDCS with aerobic training promoted additional effects in relation to the group subjected to placebo stimulation on general pain and fatigue scores, as well as on pain intensity, without changes in the subdomains of the pain and fatigue questionnaire. This trial is registered with NCT04678635.

Effect of atorvastatin on muscle tissues of dermatomyositis and antisynthetase syndrome patients with dyslipidemia.

INTRODUCTION: In a recent study, we have shown that atorvastatin is clinically safe for dermatomyositis (DM) and antisynthetase syndrome (ASS) patients with dyslipidemia. Herein, we showed in an unprecedented way, the safety of atorvastatin on the muscular tissues of these patients. METHODS: Transcriptome analysis was performed on samples of the vastus lateralis muscle obtained at baseline and after 12 weeks of atorvastatin (20 mg/day) intervention in DM or ASS patients with dyslipidemia [6DM and 5ASS received atorvastatin, and 2DM and 3ASS received placebo]. The results were analyzed considering differences in expression fold change before and after treatment. Histological and histochemical analyses were also performed. RESULTS: In both groups, no significant changes were observed in genes related to the mitochondrial, oxidative, insulin, lipid, and fibrogenic pathways. Histological analysis showed a slight variability in the fiber size that was preserved after the intervention. In addition, the mosaic of muscle fibers was preserved in the internal architecture of the fibers and all histological regions. No fiber necrosis or atrophy, focal failures, subsarcolemmal accumulation, lipids, areas of fibrosis, or alterations in mitochondrial activity were observed. All muscle fibers were labeled for MHC I. CONCLUSION: Atorvastatin did not promote significant changes in the expression of genes related to mitochondrial, oxidative, insulin, lipid, and fibrogenic pathways in the muscle tissues of DM and ASS patients with dyslipidemia. Atorvastatin did not also promote histological and histochemical changes in muscle tissues. Our results reinforce the safety of the administration of atorvastatin to treat dyslipidemia in patients with DM and ASS.

Exercise training attenuates skeletal muscle fat infiltration and improves insulin pathway of patients with immune-mediated necrotizing myopathies and dermatomyositis.

Objectives: This study aims to evaluate the effects of exercise training on intramuscular lipid content and genes related to insulin pathway in patients with systemic autoimmune myopathies (SAMs). Patients and methods: Between January 2016 and May 2019, a total of seven patients with dermatomyositis (DM; 3 males, 4 females; mean age: 49.8±2.3 years; range, 43 to 54 years), six with immune mediated necrotizing myopathy (IMNM; 3 males, 3 females; mean age: 58.5±10.6 years; range, 46 to 74 years), and 10 control individuals (CTRL group; 4 males, 6 females; mean age: 48.7±3.9 years; range, 41 to 56 years) were included. The muscle biopsy before and after the intervention was performed to evaluate the intramuscular lipid content. Patients underwent a combined exercise training program for 12 weeks. Skeletal muscle gene expression was analyzed and the DM versus CTRL group, DM pre- and post-, and IMNM pre- and post-intervention were compared. Results: The DM group had a higher intramuscular lipid content in type II muscle fibers compared to the CTRL group. After the intervention, there was a reduction of lipid content in type I and II fibers in DM and IMNM group. The CTRL group showed a significantly higher expression of genes related to insulin and lipid oxidation pathways (AMPKß2, AS160, INSR, PGC1-α, PI3K, and RAB14) compared to the DM group. After exercise training, there was an increase gene expression related to insulin pathway and lipid oxidation in DM group (AMPKß2, AS160, INSR, PGC1-α, PI3K, and RAB14) and in IMNM group (AKT2, AMPKß2, RAB10, RAB14, and PGC1-α). Conclusion: Exercise training attenuated the amount of fat in type I and II muscle fibers in patients with DM and IMNM and increased gene expression related to insulin pathways and lipid oxidation in DM and IMNM. These results suggest that exercise training can improve the quality and metabolic functions of skeletal muscle in these diseases.

Plasmin and plasminogen prevent sepsis severity by reducing neutrophil extracellular traps and systemic inflammation.

Sepsis is a lethal syndrome characterized by systemic inflammation and abnormal coagulation. Despite therapeutic advances, sepsis mortality remains substantially high. Herein, we investigated the role of the plasminogen/plasmin (Plg/Pla) system during sepsis. Plasma levels of Plg were significantly lower in mice subjected to severe compared with nonsevere sepsis, whereas systemic levels of IL-6, a marker of sepsis severity, were higher in severe sepsis. Plg levels correlated negatively with IL-6 in both septic mice and patients, whereas plasminogen activator inhibitor-1 levels correlated positively with IL-6. Plg deficiency render mice susceptible to nonsevere sepsis induced by cecal ligation and puncture (CLP), resulting in greater numbers of neutrophils and M1 macrophages, liver fibrin(ogen) deposition, lower efferocytosis, and increased IL-6 and neutrophil extracellular trap (NET) release associated with organ damage. Conversely, inflammatory features, fibrin(ogen), and organ damage were substantially reduced, and efferocytosis was increased by exogenous Pla given during CLP- and LPS-induced endotoxemia. Plg or Pla protected mice from sepsis-induced lethality and enhanced the protective effect of antibiotics. Mechanistically, Plg/Pla-afforded protection was associated with regulation of NET release, requiring Pla-protease activity and lysine binding sites. Plg/Pla are important host-protective players during sepsis, controlling local and systemic inflammation and collateral organ damage.

High prevalence of necrotising myopathy pattern in muscle biopsies of patients with anti-Jo-1 antisynthetase syndrome.

OBJECTIVES: Until now, researchers have not provided a well-defined muscle histological pattern for antisynthetase syndrome (ASSD). Therefore, we aimed to analyse the muscle biopsies of patients with anti-Jo-1 ASSD. METHODS: This study included 26 patients with anti-Jo-1 ASSD admitted for investigation of the disease and obligatorily with muscle impairment, from 2010 to 2021, whose serial frozen muscle sections were analysed. RESULTS: Patients' mean age at disease diagnosis was 42.8±11.6 years, and the female gender was most predominant. Concerning muscle biopsies, cell infiltrates were present in 76.9% of the samples, and they were mainly located at the endomysium area (70%), with a predominance of macrophages (92.9%). Fiber muscle necrosis was present in 92.3% and was diffused in 54.2%. Expression of MHC-I was seen in all samples. Samples were mostly marked by the presence of CD68+ and discreet/low CD4+ and CD8+ staining, which is consistent with a higher predominance of observed necrosis and macrophage cell infiltrates. In general, 38.5% of patients had a necrotising myopathy pattern in muscle biopsies, whereas 34.6% and 26.9% had a general inflammatory myopathy pattern and nonspecific myopathy, respectively. This necrotising myopathy pattern was not associated with the demographic, clinical, or laboratory data. CONCLUSIONS: Our data show that almost 40% of patients with well-defined anti-Jo-1 ASSD with objective muscle impairment have a necrotising myopathy pattern in their muscle biopsies. Although this pattern is more classically related to immune-mediated necrotising myopathies, in association with clinical manifestations and the presence of anti-Jo-1 autoantibodies, this characteristic may lead to ASSD diagnosis.

Impact of bedside ultrasound to reduce the incidence of acute renal injury in high-risk surgical patients: a randomized clinical trial.

PURPOSE: This study aimed to determine whether performing bedside ultrasound impacts the occurrence of acute kidney injury (AKI) in the immediate postoperative period (POP) of high-risk surgery patients. METHODS: POP patients were randomly assigned to two groups: (i) ultrasound (US) group, in which hemodynamic management was guided with clinical parameters supplemented with the bedside US findings; (ii) control group, hemodynamic management based solely on clinical parameters. Two exams were performed in the first 24 h of admission. RESULTS: Fifty-one patients were randomized to the US group and 60 to the control group. There was no significant difference for incidence of AKI in both groups assessed 12 h (31.4% vs 35.0%, P = 0.84), 24 h (27.5% vs 23.3%, P = 0.66), or 7 days (17.6 vs 8.3%, P = 0.16) after surgery. No difference was found in the amounts of volume administered over the first 12 h (1000 [500-2000] vs. 1000 [500-1500], P = 0.72) and 24 h (1000 [0-1500] vs. 1000 [0-1500], P = 0.95) between the groups. Patients without AKI in the control group received higher amounts of volume during the ICU stay. CONCLUSION: The use of bedside US in the immediate postoperative period of high-risk surgery did not show benefits in reducing AKI incidence.

Clinical manifestations, outcomes, and antibody profile of Brazilian adult patients with dermatomyositis: a single-center longitudinal study.

BACKGROUND: Currently, only a few retrospective cohort or cross-sectional studies have described the general characteristics of Brazilian patients with classical dermatomyositis (DM). In contrast, we aimed to longitudinally assess a large sample of these patients, and several myositis autoantibodies. METHODS: This single-center longitudinal study included 91 Brazilian adults with defined DM (EULAR/ACR 2017) who underwent follow-up appointments in our tertiary center from 2012 to 2021. Myositis autoantibody analysis was performed using a commercial kit. RESULTS: The mean age of the patients was 47.3 ± 15.4 years, with a predominance of female (67.0%) and White (81.3%) patients. As an initial treatment, 76.9% of the patients received methylprednisolone pulse therapy, 59.3% received intravenous immunoglobulin, and 54.9% received both drugs. The median follow-up duration was 44 months (interquartile 17-67) months. There were 92 severe episodes of infection, and neoplasms were identified in 20 patients (22.0%). Hypertension was identified in 46.2% of patients, whereas diabetes mellitus and myocardial infarction occurred in 19.8% and 4.4%, respectively. Nine patients died during the follow-up. At the last visit, one-third of the patients had disease activity, half had a complete clinical response, and one-fifth were in disease remission. In a univariate logistic regression, anti-aminoacyl-tRNA synthetase antibodies (n = 13) were associated with interstitial lung disease, "mechanic's hands", and anti-Ro-52, and had an inverse association with "V"-neck and "shawl" signs. Anti-MDA-5 (n = 10) were associated with male gender, digital ulcers, vasculitis, arthritis, anti-Ro-52, and active disease. Anti-Ro-52 (n = 26) were associated with "mechanics' hands", arthritis, interstitial lung disease, anti-tRNA synthetases, and anti-MDA-5. No association was found for anti-Mi-2 (n = 10). CONCLUSIONS: This study shows the general profile of a significant sample of Brazilian patients with DM as well as the association of some antibodies with clinical and laboratory manifestations of this myositis.

Synchronous Teleconsultation and Monitoring Service Targeting COVID-19: Leveraging Insights for Postpandemic Health Care.

BACKGROUND: Although a great number of teleconsultation services have been developed during the COVID-19 pandemic, studies assessing usability and health care provider satisfaction are still incipient. OBJECTIVE: This study aimed to describe the development, implementation, and expansion of a synchronous teleconsultation service targeting patients with symptoms of COVID-19 in Brazil, as well as to assess its usability and health care professionals' satisfaction. METHODS: This mixed methods study was developed in 5 phases: (1) the identification of components, technical and functional requirements, and system architecture; (2) system and user interface development and validation; (3) pilot-testing in the city of Divinópolis; (4) expansion in the cities of Divinópolis, Teófilo Otoni, and Belo Horizonte for Universidade Federal de Minas Gerais faculty and students; and (5) usability and satisfaction assessment, using Likert-scale and open-ended questions. RESULTS: During pilot development, problems contacting users were solved by introducing standardized SMS text messages, which were sent to users to obtain their feedback and keep track of them. Until April 2022, the expanded system served 31,966 patients in 146,158 teleconsultations. Teleconsultations were initiated through chatbot in 27.7% (40,486/146,158) of cases. Teleconsultation efficiency per city was 93.7% (13,317/14,212) in Teófilo Otoni, 92.4% (11,747/12,713) in Divinópolis, and 98.8% (4981/5041) in Belo Horizonte (university campus), thus avoiding in-person assistance for a great majority of patients. In total, 50 (83%) out of 60 health care professionals assessed the system's usability as satisfactory, despite a few system instability problems. CONCLUSIONS: The system provided updated information about COVID-19 and enabled remote care for thousands of patients, which evidenced the critical role of telemedicine in expanding emergency services capacity during the pandemic. The dynamic nature of the current pandemic required fast planning, implementation, development, and updates in the system. Usability and satisfaction assessment was key to identifying areas for improvement. The experience reported here is expected to inform telemedicine strategies to be implemented in a postpandemic scenario.

High prevalence of fatigue in patients with Takayasu arteritis: a case-control study in a Brazilian centre.

Objectives: Several studies have shown not only a high prevalence of fatigue but also a reduction in health-related quality of life (HRQoL) in patients with rheumatic diseases. Owing to insufficient research in this area, we aimed to assess the prevalence of fatigue and its contribution to impairment of HRQoL in patients with Takayasu arteritis (TAK). Methods: This single-centre case-control study included 53 TAK patients who were matched by age, BMI and sex with 100 healthy individuals. Aside from the patients' general data, the following information was collected: disease activity, level of activities of daily living (HAQ), physical activity levels and chronic fatigue. Results: The TAK patients and healthy individuals were comparable in terms of current age, BMI and sex distribution. The median disease duration of TAK was 13.0 (7.0-20.0) years, and 11 (20.8%) patients had active disease. Compared with healthy individuals, patients with TAK had a higher prevalence of fatigue and lower HAQ score, physical activity level and intensity, and physical and psychosocial domains of the modified fatigue impact scale (P < 0.01). Moreover, TAK patients had increased fatigue rates compared with the healthy individuals (fatigue severity scale: odds ratio = 2.6; 95% CI = 1.2, 5.4; modified fatigue impact scale: odds ratio = 2.6; 95% CI = 1.2, 5.5). Fatigue was positively correlated with worsening HAQ, CRP levels, daily prednisone dose and disease activity, and negatively correlated with disease duration. Conclusion: TAK patients have a higher prevalence of fatigue, which affects different aspects of the disease, including physical function. Thus, fatigue-focused treatments should also be considered in clinical practice. Trial registration: The Brazilian Clinical Trials Registry (ReBEC), https://ensaiosclinicos.gov.br/, RBR-9n4z2hh.

High prevalence of necrotizing myofibers in adult dermatomyositis muscle biopsies.

INTRODUCTION/OBJECTIVES: This study aimed to analyze the presence, grade, and relevance of myofiber necrosis in the muscle tissues of patients with adult dermatomyositis. Second, these parameters were associated with the patients' demographic, clinical, and laboratory data. METHOD: This was a retrospective study, from 2001 to 2021, which included 89 muscle biopsies of patients with definite dermatomyositis performed at the time of diagnostic investigation. Immunohistochemical analysis was performed on serially frozen muscle sections. The presence and degree of endomysial/perifascicular myofiber necrosis were also analyzed. The degree of necrosis was semi-quantitatively coded as absent/mild, moderate, or severe. The presence or absence of perifascicular atrophy and also perivascular lymphomononuclear infiltration was also evaluated. RESULTS: Muscle biopsies from 89 patients, the majority of whom were Caucasian women, were evaluated. Both perifascicular atrophy and perivascular lymphomononuclear infiltrates were observed in 76 (85.4%) samples. Moderate or intense areas of myofiber necrosis in endomysial/perifascicular areas were found in 30/89 (33.7%) and 14/89 (15.7%) muscle biopsies, respectively, with a predominance of macrophagic infiltrate in relation to lymphomononuclear cells in these regions. The degree of muscle weakness in the limbs (upper and lower) was associated only with areas of intense myofiber necrosis. CONCLUSIONS: A high prevalence of myofiber necrosis was observed, which patients resembled the initial clinical feature of patients with immune-mediated necrotizing myopathies. Key Point • A high prevalence of myofiber necrosis was observed in muscle biopsies of patients with dermatomyositis.

Systemic autoimmune myopathies: a prospective phase 4 controlled trial of an inactivated virus vaccine against SARS-CoV-2.

OBJECTIVES: To evaluate immunogenicity and safety of an inactivated SARS-CoV-2 vaccine in systemic autoimmune myopathies (SAMs) and the possible influence of baseline disease parameters, comorbidities and therapy on immune response. METHODS: This prospective controlled study included 53 patients with SAMs and 106 non-immunocompromised control group (CTRL). All participants received two doses of the Sinovac-CoronaVac vaccine (28-day interval). Immunogenicity was assessed by anti-SARS-CoV-2 S1/S2 IgG seroconversion (SC), anti-S1/S2 IgG geometric mean titre (GMT), factor increase GMT (FI-GMT), neutralizing antibodies (NAb) positivity, and median neutralizing activity after each vaccine dose (D0 and D28) and six weeks after the second dose (D69). Participants with pre-vaccination positive IgG serology and/or NAb and those with RT-PCR confirmed COVID-19 during the protocol were excluded from immunogenicity analysis. RESULTS: Patients and CTRL had comparable sex (P>0.99) and age (P=0.90). Immunogenicity of 37 patients and 79 CTRL-naïve participants revealed at D69, a moderate but significantly lower SC (64.9% vs 91.1%, P<0.001), GMT [7.9 (95%CI 4.7-13.2) vs 24.7 (95%CI 30.0-30.5) UA/ml, P<0.001] and frequency of NAb (51.4% vs 77.2%, P<0.001) in SAMs compared with CTRL. Median neutralizing activity was comparable in both groups [57.2% (interquartile range (IQR) 43.4-83.4) vs 63.0% (IQR 40.3-80.7), P=0.808]. Immunosuppressives were less frequently used among NAb+ patients vs NAb- patients (73.7% vs 100%, P=0.046). Type of SAMs, disease status, other drugs or comorbidities did not influence immunogenicity. Vaccine-related adverse events were mild with similar frequencies in patients and CTRL (P>0.05). CONCLUSION: Sinovac-CoronaVac is safe and has a moderate short-term immunogenicity in SAMs, but reduced compared with CTRL. We further identified that immunosuppression is associated with diminished NAb positivity. TRIAL REGISTRATION: COVID-19 CoronaVac in Patients With Autoimmune Rheumatic Diseases and HIV/AIDS (CoronavRheum), http://clinicaltrials.gov/ct2/show/NCT04754698.

Characterization of Patients With Dermatomyositis According to Anti-Melanoma Differentiation-Associated Gene-5 Autoantibodies in Centers from 3 Latin American Countries: A Cohort Study.

BACKGROUND/OBJECTIVE: The anti-melanoma differentiation-associated protein 5 (MDA5) autoantibodies have been associated with a high frequency of interstitial lung disease (ILD) and rapidly progressive ILD (RP-ILD) in dermatomyositis (DM) patients, mainly in Asian subjects. However, there is scarce information about these parameters in Latin American patients. METHOD: This was a medical records review cohort study that included classic DM (CDM) and clinically amyopathic DM (CADM) patients from 3 Latin American countries (Argentina, Brazil, and Mexico). RESULTS: A total of 270 DM patients were evaluated: 25.9% with CADM and 74.1% with CDM. The overall prevalence of ILD and RP-ILD, respectively, was 70 (25.9%) and 4 (1.5%) of the 270 patients, and the distributions were comparable between patients with CDM and CADM. The anti-MDA5 was present in 31 (25.4%) of 122 CDM patients and in 17 (48.6%) of 35 CADM patients; it was not associated with presence of ILD and RP-ILD. However, anti-MDA5-positive CDM patients had significantly high frequency of "mechanic's hands," arthralgia, arthritis, and lower serum levels of creatine phosphokinase, whereas anti-MDA5-positive CADM patients had significantly high frequency of arthritis. Pulmonary infection and ILD are main causes of death in DM patients. CONCLUSIONS: In the present study, the prevalence of ILD in DM patients is comparable to that described in the literature, in contrast to the very low frequency of RP-ILD. In addition, the anti-MDA5 is not associated with ILD and RP-ILD, but anti-MDA5-positive DM patients present conditions that mimic antisynthetase syndrome. Pulmonary infection and ILD were the main causes of death in our sample.

Reproductive benefits associated with dispersal in headwater populations of Trinidadian guppies (Poecilia reticulata).

Theory suggests that the evolution of dispersal is balanced by its fitness costs and benefits, yet empirical evidence is sparse due to the difficulties of measuring dispersal and fitness in natural populations. Here, we use spatially explicit data from a multi-generational capture-mark-recapture study of two populations of Trinidadian guppies (Poecilia reticulata) along with pedigrees to test whether there are fitness benefits correlated with dispersal. Combining these ecological and molecular data sets allows us to directly measure the relationship between movement and reproduction. Individual dispersal was measured as the total distance moved by a fish during its lifetime. We analysed the effects of dispersal propensity and distance on a variety of reproductive metrics. We found that number of mates and number of offspring were positively correlated to dispersal, especially for males. Our results also reveal individual and environmental variation in dispersal, with sex, size, season, and stream acting as determining factors.

Physical exercise for the management of systemic autoimmune myopathies: recent findings, and future perspectives.

PURPOSE OF REVIEW: The aim of this review is to present the main pieces of evidence, recent literature and to present future perspectives on the use of exercise/physical training in the treatment and improvement of the quality of life of patients with systemic autoimmune myopathies. RECENT FINDINGS: In the last decades, knowledge about the relevance of physical exercise training in preventing and treating chronic diseases and improving quality of life has grown. Following the global trend exemplified by the expression 'exercise is medicine', the importance of exercise/physical training has also grown in myopathies. However, the science of exercise has a lot to collaborate on and improve patients' quality of life with myopathies by appropriating new technological tools, including accessible and low-cost devices and smartphone apps. SUMMARY: Physical exercise, as already consolidated in the literature, is an effective, well tolerated, and low-cost strategy for patients with myopathies. The use of wearable devices, smartphone apps, and online training prescriptions must accompany the global scenario, bringing new research fields and expanding the options for access to training for the individualized basis, and prescribed by qualified professionals.

Effect of exercise training on fatigue and pain in patients with systemic autoimmune myopathies: A systematic review.

Systemic autoimmune myopathies (or idiopathic inflammatory myopathies) are a wide group of rare rheumatic diseases characterized by muscle weakness due to muscle inflammation. Recent evidence has continually reinforced the relevance of the perception of pain and fatigue as parameters of notable contribution to reducing the quality of life of these patients. However, due to the multidimensional characteristic of these variables, few studies address the effects of pharmacological and non-pharmacological therapies, such as exercise training on these variables. With regard to patients with systemic autoimmune myopathies, the outcomes related to the effects of exercise training are focused on muscle strength and endurance, few explore the effects on the perception of pain and fatigue. Given this, studies that review systematically the available evidence of the effects of exercise training on these perceptions can contribute to management of this parameter in clinical practice. Given this context, the present study aims to review systematically the effectiveness of exercise training specifically on the perception of pain and fatigue.

Exercise Training Attenuates Ubiquitin-Proteasome Pathway and Increases the Genes Related to Autophagy on the Skeletal Muscle of Patients With Inflammatory Myopathies.

BACKGROUND/OBJECTIVE: The aim of this study was to evaluate the effects of exercise training on the ubiquitin-proteasome system (UPS) and genes related to autophagy on the skeletal muscle of patients with dermatomyositis (DM) and immune-mediated necrotizing myopathies (IMNMs). METHODS: Seven DM patients and 6 IMNM patients were treated for 12 weeks with a twice-weekly aerobic and resistance training exercise program. Aerobic capacity, muscle strength, and expression of genes in the skeletal muscle related to UPS and to autophagy were evaluated at the baseline and after the intervention. Moreover, only at the baseline, 10 healthy control individuals were also evaluated. RESULTS: The age of DM and IMNM patients was 49.8 and 58.5 years, respectively. Genes related to UPS were upregulated, whereas genes related to autophagy and antioxidative systems were downregulated only in the DM group when compared with control group. After completion of the exercise training program, several genes related to UPS were downregulated, whereas genes related to autophagy, mitochondrial pathways, and antioxidative systems were upregulated in both the DM and IMNM groups. CONCLUSIONS: Exercise training can increase genes related to autophagy, mitophagy, and lysosomal biogenesis in the skeletal muscle of patients. These results suggest an increase in the recycling of damaged proteins and organelles, which may also contribute to the performance and endurance of skeletal muscles in these patients. Furthermore, in patients with myositis, exercise training led to a decrease in genes related to UPS and an increase in genes related to antioxidative capacity. Therefore, this may also contribute to an attenuation of skeletal muscle loss and of the deleterious effects of oxidative stress on the skeletal muscle of these patients.

Lung Ultrasound Can Predict the Clinical Course and Severity of COVID-19 Disease.

Coronavirus disease 2019 (COVID-19) compromises the lung in large numbers of people. The development of minimally invasive methods to determine the severity of pulmonary extension is desired. This study aimed to describe the characteristics of sequential lung ultrasound and to test the prognostic usefulness of this exam in a group of patients admitted to the hospital with COVID-19. We prospectively evaluated patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection admitted to our hospital between April and August 2020. Bedside lung ultrasound exams were performed at three time points: at inclusion in the study, after 48 h and on the seventh day of follow-up. Lung ultrasound scores were quantified according to the aeration loss in each of eight zones scanned. Sixty-six participants were included: 42 (63.6%) in the intensive care unit and 24 (36.3%) in the ward. Lung ultrasound scores were higher in participants admitted to the intensive care unit than in those admitted to the ward at the time of inclusion (16 [13-17] vs. 10 [4-14], p < 0.001), after 48 h (15.5 [13-17] vs. 12.5 [8.2-14.7], p = 0.001) and on the seventh day (16 [14-17] vs. 7 [4.5-13.7], p < 0.001) respectively. Lung ultrasound score measured at the time of inclusion in the study was independently associated with the need for admission to the intensive care unit (odds ratio = 1.480; 95% confidence interval, 1.093-2.004; p = 0.011) adjusted by the Sequential Organ Failure Assessment score.

Repeated evolution of underwater rebreathing in diving Anolis lizards.

Air-based respiration limits the use of aquatic environments by ancestrally terrestrial animals. To overcome this challenge, diving arthropods have evolved to respire without resurfacing using air held between their cuticle and surrounding water.1-4 Inspired by natural history observations in Haiti (unpublished data) and Costa Rica,5,6 we conducted experiments documenting routine air-based underwater respiration in several distantly related semi-aquatic Anolis lizard species. Semi-aquatic anoles live along neotropical streams and frequently dive for refuge or food,7-12 remaining underwater for up to 18 min. While submerged, these lizards iteratively expire and re-inspire narial air bubbles-underwater "rebreathing." Rebreathed air is used in respiration, as the partial pressure of oxygen in the bubbles decreases with experimental submersion time in living anoles, but not in mechanical controls. Non-aquatic anoles occasionally rebreathe when submerged but exhibit more rudimentary rebreathing behaviors. Anole rebreathing is facilitated by a thin air layer (i.e., a "plastron," sensu Brocher13) supported by the animal's rugose skin upon submergence. We suggest that hydrophobic skin, which we observed in all sampled anoles,14,15 may have been exaptative, facilitating the repeated evolution of specialized rebreathing in species that regularly dive. Phylogenetic analyses strongly suggest that specialized rebreathing is adaptive for semi-aquatic habitat specialists. Air-based rebreathing may enhance dive performance by incorporating dead space air from the buccal cavity or plastron into the lungs, facilitating clearance of carbon dioxide, or allowing uptake of oxygen from surrounding water (i.e., a "physical gill" mechanism4,16).

Increased modifiable cardiovascular risk factors in patients with Takayasu arteritis: a multicenter cross-sectional study.

BACKGROUND: Modifiable cardiovascular risk factors (MCRFs), such as those related to aerobic capacity, muscle strength, physical activity, and body composition, have been poorly studied in Takayasu arteritis (TAK). Therefore, the aim of the study was to investigate MCRFs and their relationships with disease status and comorbidities among patients with TAK. METHODS: A multicenter cross-sectional study was conducted between 2019 and 2020, in which 20 adult women with TAK were compared with 16 healthy controls matched by gender, age, and body mass index. The following parameters were analyzed: aerobic capacity by cardiopulmonary test; muscle function by timed-stands test, timed up-and-go test, and handgrip test; muscle strength by one-repetition maximum test and handgrip test; body composition by densitometry; physical activity and metabolic equivalent by IPAQ, quality of life by HAQ and SF-36; disease activity by ITAS2010 and NIH score; and presence of comorbidities. RESULTS: Patients with TAK had a mean age of 41.5 (38.0-46.3) years, disease duration of 16.0 (9.5-20.0) years, and a mean BMI of 27.7±4.5 kg/m2. Three out of the 20 patients with TAK had active disease. Regarding comorbidities, 16 patients had systemic arterial hypertension, 11 had dyslipidemia, and two had type 2 diabetes mellitus, while the control group had no comorbidities. TAK had a significant reduction in aerobic capacity (absolute and relative VO2 peak), muscle strength in the lower limbs, increased visceral adipose tissue, waist-to-hip ratio, reduced walking capacity, decreased weekly metabolic equivalent, and quality of life (P< 0.05) as compared to controls. However, there were no correlations between these MCRFs parameters and disease activity. CONCLUSIONS: TAK show impairment in MCRFs; therefore, strategies able to improve MCRF should be considered in this disease.

Safety of Atorvastatin in Patients With Stable Systemic Autoimmune Myopathies: A Pilot Longitudinal Study.

BACKGROUND/OBJECTIVE: Patients with systemic autoimmune myopathies (SAMs) have high prevalence of dyslipidemia and, consequently, possible endothelial dysfunction and vascular stiffness. Our objective was to evaluate the possible benefits on endothelial function and vascular stiffness, as well as adverse effects of atorvastatin in SAMs. METHODS: A pilot longitudinal, double-blind, randomized, placebo-controlled study was conducted. Twenty-four of 242 patients were randomized at a 2:1 ratio to receive atorvastatin (20 mg/d) or placebo for a period of 12 weeks. Demographic data, comorbidities, and clinical and laboratory parameters, as well as endothelial function and arterial stiffness, were evaluated. RESULTS: Of the 24 randomized patients, 4 patients were excluded, with remaining 20 patients (14 in the atorvastatin group and 6 in the placebo group). The mean age of the patients was 49.0 years, and 75% of the patients were female. At baseline, the demographic data, disease status, treatment, cardiovascular comorbidities, and risk factors were comparable between the atorvastatin and placebo groups. After 12 weeks of follow-up of atorvastatin therapy, no improvements were observed for endothelial function and arterial stiffness in either group (p > 0.05). As expected, a significant reduction in total and low-density lipoprotein cholesterol levels was observed. During the study, no clinical intercurrences or disease relapses were observed in either group. CONCLUSIONS: The atorvastatin drug attenuated low-density lipoprotein cholesterol without worsening clinical outcomes in SAMs. No change was observed for endothelial function and arterial stiffness. Additional studies, with long-term follow-up time and different atorvastatin dosage, are needed to corroborate the results of this study.