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    Outcomes of 847 childhood-onset systemic lupus erythematosus patients in three age groups
    (Sage Publications Ltd, 2017) Lopes, S. R. M.; Gormezano, N. W. S.; Gomes, R. C.; Aikawa, N. E.; Pereira, R. M. R.; Terreri, M. T. [UNIFESP]; Magalhaes, C. S.; Ferreira, J. C.; Okuda, E. M.; Sakamoto, A. P. [UNIFESP]; Sallum, A. M. E.; Appenzeller, S.; Ferriani, V. P. L.; Barbosa, C. M.; Lotufo, S.; Jesus, A. A.; Andrade, L. E. C. [UNIFESP]; Campos, L. M. A.; Bonfa, E.; Silva, C. A.
    Objective The objective of this study was to assess outcomes of childhood systemic lupus erythematosus (cSLE) in three different age groups evaluated at last visit: group A early-onset disease (<6 years), group B school age (6 and <12 years) and group C adolescent (12 and <18 years). Methods An observational cohort study was performed in ten pediatric rheumatology centers, including 847 cSLE patients. Results Group A had 39 (4%), B 395 (47%) and C 413 (49%). Median disease duration was significantly higher in group A compared to groups B and C (8.3 (0.1-23.4) vs 6.2 (0-17) vs 3.3 (0-14.6) years, p<0.0001). The median Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (SLICC/ACR-DI) (0 (0-9) vs 0 (0-6) vs 0 (0-7), p=0.065) was comparable in the three groups. Further analysis of organ/system damage revealed that frequencies of neuropsychiatric (21% vs 10% vs 7%, p=0.007), skin (10% vs 1% vs 3%, p=0.002) and peripheral vascular involvements (5% vs 3% vs 0.3%, p=0.008) were more often observed in group A compared to groups B and C. Frequencies of severe cumulative lupus manifestations such as nephritis, thrombocytopenia, and autoimmune hemolytic anemia were similar in all groups (p>0.05). Mortality rate was significantly higher in group A compared to groups B and C (15% vs 10% vs 6%, p=0.028). Out of 69 deaths, 33/69 (48%) occurred within the first two years after diagnosis. Infections accounted for 54/69 (78%) of the deaths and 38/54 (70%) had concomitant disease activity. Conclusions This large multicenter study provided evidence that early-onset cSLE group had distinct outcomes. This group was characterized by higher mortality rate and neuropsychiatric/vascular/skin organ damage in spite of comparable frequencies of severe cumulative lupus manifestations. We also identified that overall death in cSLE patients was an early event mainly attributed to infection associated with disease activity.
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    Aerobic exercise reduces hippocampal ERK and p38 activation and improves memory of middle-aged rats
    (Wiley, 2017) Cardoso, Fabrizio dos Santos; Franca, Erivelton Fernandes; Serra, Fernando Tadeu; Victorino, Angelica Begatti [UNIFESP]; de Almeida, Alexandre Aparecido [UNIFESP]; Fernandes, Jansen [UNIFESP]; Cabral, Francisco Romero; Venancio, Daniel Paulino; Arida, Ricardo Mario [UNIFESP]; da Silva, Sergio Gomes
    Aging is often accompanied by cognitive decline, memory impairment, and an increased susceptibility to neurodegenerative disorders. Although the physiological processes of aging are not fully understood, these age-related changes have been interpreted by means of various cellular and molecular theories. Among these theories, alterations in the intracellular signaling pathways associated with cell growth, proliferation, and survival have been highlighted. Based on these observations and on recent evidence showing the beneficial effects of exercise on cognitive function in the elderly, we investigated the cell signaling pathways in the hippocampal formation of middle-aged rats (18months old) submitted to treadmill exercise over 10 days. To do this, we evaluated the hippocampal activation of intracellular signaling proteins linked to cell growth, proliferation, and survival, such as Akt, mTOR, p70S6K, ERK, CREB, and p38. We also explored the cognitive performance (inhibitory avoidance) of middle-aged rats. It was found that physical exercise reduces ERK and p38 activation in the hippocampal formation of aged rats, when compared to the control group. The hippocampal activation and expression of Akt, mTOR, p70S6K, and CREB were not statistically different between the groups. It was also observed that aged rats from the exercise group exhibited better cognitive performance in the inhibitory avoidance task (aversive memory) than aged rats from the control group. Our results indicate that physical exercise reduces intracellular signaling pathways linked to inflammation and cell death (i.e., ERK and p38) and improves memory in middle-aged rats.
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    Inflammasome gene profile is modulated in septic patients, with a greater magnitude in non-survivors
    (Wiley, 2017) Esquerdo, K. F. [UNIFESP]; Sharma, N. K. [UNIFESP]; Brunialti, M. K. C. [UNIFESP]; Baggio-Zappia, G. L. [UNIFESP]; Assuncao, M.; Azevedo, L. C. P.; Bafi, A. T. [UNIFESP]; Salomao, R. [UNIFESP]
    Inflammasome signalling induces the processing and secretion of interleukin (IL)-1 and IL-18 which, coupled with pyroptosis, activate further the inflammatory response. In the present study we evaluated the expression of genes involved in inflammasome signalling pathways in septic patients, their interaction networks and the predicted functions modulated in survivors and non-survivors. Twenty-seven patients with sepsis secondary to community-acquired pneumonia admitted to intensive care units from three general hospitals in SAo Paulo were included into the study. We performed a polymerase chain reaction (PCR) array encompassing 35 genes related to the nucleotide-binding oligomerization domain and leucine-rich repeat-containing (NLR)-inflammasome in peripheral blood mononuclear cells obtained at admission and after 7 days of follow-up. Eleven healthy volunteers were used as the reference group. Increased NLRC4 and NLRP3 and decreased nucleotide-binding oligomerization domain (NOD1), and NLRP1 expression was observed in septic patients compared to healthy individuals
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    Production of primordial gravitational waves in a simple class of running vacuum cosmologies
    (World Scientific Publ Co Pte Ltd, 2017) Tamayo, D. A.; Lima, J. A. S.; Bessada, D. F. A. [UNIFESP]
    The problem of cosmological production of gravitational waves (GWs) is discussed in the framework of an expanding, spatially homogeneous and isotropic FRW type universe with time-evolving vacuum energy density. The GW equation is established and its modified time-dependent part is analytically resolved for different epochs in the case of a flat geometry. Unlike the standard Lambda CDM cosmology (no interacting vacuum), we show that GWs are produced in the radiation era even in the context of general relativity. We also show that for all values of the free parameter, the high frequency modes are damped out even faster than in the standard cosmology both in the radiation and matter-vacuum dominated epoch. The formation of the stochastic background of gravitons and the remnant power spectrum generated at different cosmological eras are also explicitly evaluated. It is argued that measurements of the CMB polarization (B-modes) and its comparison with the rigid Lambda CDM model plus the inflationary paradigm may become a crucial test for dynamical dark energy models in the near future.
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    Physiological Requirements to Perform the Glittre Activities of Daily Living Test by Subjects With Mild-to-Severe COPD
    (Daedalus Enterprises Inc, 2017) Souza, Gerson F. [UNIFESP]; Moreira, Graciane L. [UNIFESP]; Tufanin, Andrea [UNIFESP]; Gazzotti, Mariana R. [UNIFESP]; Castro, Antonio A. [UNIFESP]; Jardim, Jose R. [UNIFESP]; Nascimento, Oliver A. [UNIFESP]
    BACKGROUND: The Glittre activities of daily living (ADL) test is supposed to evaluate the functional capacity of COPD patients. The physiological requirements of the test and the time taken to perform it by COPD patients in different disease stages are not well known. The objective of this work was to compare the metabolic, ventilatory, and cardiac requirements and the time taken to carry out the Glittre ADL test by COPD subjects with mild, moderate, and severe disease. METHODS: Spirometry, Medical Research Council questionnaire, cardiopulmonary exercise test, and 2 Glittre ADL tests were evaluated in 62 COPD subjects. Oxygen uptake ((V)over dot(O2)), carbon dioxide production, pulmonary ventilation, breathing frequency, heart rate, S-pO2, and dyspnea were analyzed before and at the end of the tests. Maximum voluntary ventilation, Glittre peak (V)over dot(O2)/cardiopulmonary exercise test (CPET) peak (V)over dot(O2), Glittre (V)over dot(E)/maximum voluntary ventilation, and Glittre peak heart rate/CPET peak heart rate ratios were calculated to analyze their reserves. RESULTS: Subjects carried out the Glittre ADL test with similar absolute metabolic, ventilatory, and cardiac requirements. Ventilatory reserve decreased progressively from mild to severe COPD subjects (P < .001 for Global Initiative for Chronic Obstructive Lung Disease [GOLD] 1 vs GOLD 2, P < .001 for GOLD 1 vs GOLD 3, and P < .001 for GOLD 2 vs GOLD 3). Severe subjects with COPD presented a significantly lower metabolic reserve than the mild and moderate subjects (P = .006 and P = .043, respectively) and significantly lower Glittre peak heart rate/CPET peak heart rate than mild subjects (P = .01). Time taken to carry out the Glittre ADL test was similar among the groups (P = .82 for GOLD 1 vs GOLD 2, P = .19 for GOLD 1 vs GOLD 3, and P = .45 for GOLD 2 vs GOLD 3). CONCLUSIONS: As the degree of air-flow obstruction progresses, the COPD subjects present significant lower ventilatory reserve to perform the Glittre ADL test. In addition, metabolic and cardiac reserves may differentiate the severe subjects. These variables may be better measures to differentiate functional performance than Glittre ADL time.