Resumo em Inglês:

Sepsis remains a major cause of morbidity and mortality worldwide, with increased burden in low- and middle-resource settings. The role of the inflammatory response in the pathogenesis of the syndrome has supported the modern concept of sepsis. Nevertheless, a definition of sepsis and the criteria for its recognition is a continuous process, which reflects the growing knowledge of its mechanisms and the success and failure of diagnostic and therapeutic interventions. Here we review the evolving concepts of sepsis, from the “systemic inflammatory response syndrome triggered by infection” (Sepsis-1) to “a severe, potentially fatal, organic dysfunction caused by an inadequate or dysregulated host response to infection” (Sepsis-3). We focused in the pathophysiology behind the concept and the criteria for recognition and diagnosis of sepsis. A major challenge in evaluating the host response in sepsis is to characterize what is protective and what is harmful, and we discuss that, at least in part, the apparent dysregulated host response may be an effort to adapt to a hostile environment. The new criteria for recognition and diagnosis of sepsis were derived from robust databases, restricted, however, to developed countries. Since then, the criteria have been supported in different clinical settings and in different economic and epidemiological contexts, but still raise discussion regarding their use for the identification versus the prognostication of the septic patient. Clinicians should not be restricted to definition criteria when evaluating patients with infection and should wisely use the broad array of information obtained by rigorous clinical observation.

Resumo em Inglês:

Elite judo demands high levels of physical and psychological skills. The brain-derived neurotrophic factor (BDNF) may be of particular interest in sports medicine for its ability to promote neuroplasticity. We investigated the plasma BDNF before and after a judo training session (Randori) and the maximal incremental ramp test (MIRT) in athletes from the Brazilian national judo team and compared the results between both exercise stimuli and sexes. Fifty-six elite judo athletes were recruited who performed each task on a separated day. Anthropometric, physiological, athletic parameters, and plasma BDNF levels were measured before and after the tasks (Randori and MIRT). The groups presented similar anthropometric and physiological characteristics at baseline for the two tasks. All athletes reached maximal performance for the tasks. Plasma levels of BDNF increased significantly after Randori and MIRT for all subjects, both men and women. When comparing both exercise stimuli, a greater increase in BDNF was observed after Randori. There was no significant difference in the delta BDNF between sexes. Our findings indicate that training specificity of sport gestures influenced the increase of blood BDNF levels.

Resumo em Inglês:

Frailty is related to a decrease in the physiological reserves, which causes difficulties in maintaining homeostasis. An example of physiological mechanisms for cardiovascular homeostasis is the baroreflex. The aim of this study was to compare baroreflex among frail, prefrail, and nonfrail individuals, in supine and orthostatic positions. Community-dwelling older adults were evaluated and categorized into frail, prefrail, or nonfrail groups, according to frailty phenotype. The RR interval (RRi) and systolic blood pressure (SBP) series were recorded for 15 min in the supine and 15 min in the orthostatic positions. Mean and variance of RRi and SBP, and baroreflex evaluated by phase, gain (α), and coherence (K2) were determined. A two-way repeated measures ANOVA, with Tukey's post hoc, was applied for group, position, and their interaction effects. The significance level established was 5%. Prefrail and frail participants did not present a significant decrease in mean values of RRi after postural challenge (893.43 to 834.20 ms and 925.99 to 857.98 ms, respectively). Frail participants showed a reduction in RRi variance in supine to orthostatic (852.04 to 232.37 ms2). Prefrail and frail participants showed a decrease in K2 after postural change (0.69 to 0.52 and 0.54 to 0.34, respectively). Frail participants exhibited lower values of K2 (0.34) compared to nonfrail and prefrail participants (0.61 and 0.52, respectively). Baroreflex indicated the presence of decoupling between heart period and SBP in frail and prefrail. Thus, reduced K2 might be a marker of the frailty process.

Resumo em Inglês:

The aim of the study was to evaluate the diagnostic accuracy of thromboelastometry for assessing rivaroxaban concentrations. The accuracy of thromboelastometry was compared with the high-performance liquid chromatography tandem mass spectrometry (HPLC-MS/MS) method, which is the gold standard for drug plasma monitoring (the reference standard). Forty-six clinically stable patients were treated with 10, 15, or 20 mg of rivaroxaban once daily (OD group) or 15 mg twice a day (BID group) (no particular indication for treatment). Patient samples were collected 2 h after the use of the medication (peak) and 2 h before the next dose (trough). The rivaroxaban plasma concentrations were determined via HPLC-MS/MS, and thromboelastometry was performed using a ROTEM® delta analyzer. There were significant prolongations in clotting time (CT) for the 10, 15, and 20 mg of rivaroxaban treatments in the OD groups. In the 15 mg BID group, the responses at the peak and trough times were similar. At the peak times, there was a positive correlation between the plasma concentration of rivaroxaban and CT (Spearman correlation rho=0.788, P<0.001) and clot formation time (rho=0.784, P<0.001), and a negative correlation for alpha angle (rho=−0.771, P<0.001), amplitude after 5 min (rho=−0.763, P<0.001), and amplitude after 10 min (rho=−0.680, P<0.001). The CT presented higher specificity and sensitivity using the cut-off determined by the receiver characteristics curve. ROTEM has potential as screening tool to measure possible bleeding risk associated with rivaroxaban plasma levels.

Resumo em Inglês:

The aim of this study was to perform an updated meta-analysis to quantitatively investigate the association between G20210A polymorphism of Prothrombin gene and the risk of retinal vein occlusion (RVO), based on the available publications with inconsistent results. We utilized the Stata software to perform the heterogeneity test, association test, Begg's and Egger's tests, and sensitivity analysis. We searched three on-line databases (PubMed, Embase, and WOS) and obtained a total of 422 articles. Based on our selection criteria, 24 case-control studies were finally enrolled in this overall meta-analysis; a subgroup analysis by the factors ethnicity, control source, and RVO type was done. Through the association test of overall meta-analysis, we did not observe a significant difference between RVO cases and controls under the A vs G (allele) (z=1.49, P=0.137), A vs G (carrier) (z=1.42, P =0.155), GA vs GG (z=1.50, P=0.135), and GA+AA vs GG (z=1.50, P=0.135). Furthermore, we observed similar negative results in the association test of subgroup analysis (all P>0.05). Heterogeneity, Begg's, and Egger's tests excluded the presence of high heterogeneity and publication bias. Statistically stable results were observed in the sensitivity analyses. Based on integrated analysis of the current evidence, Prothrombin gene G20210A polymorphism is likely unrelated to the risk of RVO.

Resumo em Inglês:

Benzyl isothiocyanate (BITC) has been shown to inhibit invasion and induce apoptosis of various types of cancer. However, its role on human oral squamous cell carcinoma (OSCC) cells is still not well elucidated. In the present study, we investigated the effect of BITC on apoptosis and invasion of SCC9 cells, and its underlying mechanisms in vitro and in vivo. SCC9 cells were exposed to BITC (5 and 25 μM) for 24 and 48 h. Cell growth, apoptosis, invasion, and migration were detected in vitro by MTT, FITC-conjugated annexin V/propidium iodide staining followed by flow cytometry, Matrigel-coated semi-permeable modified Boyden, and wound-healing assay. S100A4, PUMA, and MMP-9 expressions were detected to investigate its mechanisms. Xenotransplantation experiments were used to investigate the role of BITC on tumor growth and lung metastasis. BITC inhibited cell viability and induced cell apoptosis in a dose- and time-dependent manner through upregulation of PUMA signals. BITC inhibited cell invasion and migration by downregulation of S100A4 dependent MMP-9 signals. The ip administration of BITC reduced tumor growth but not lung metastasis of SCC9 cells subcutaneously implanted in nude mice. BITC treatment activated pro-apoptotic PUMA and inhibited S100A4-dependent MMP-9 signals, resulting in the inhibition of cell growth and invasion in cultured and xenografted SCC9 cells. Thereby, BITC is a potential therapeutic approach for OSCC.

Resumo em Inglês:

We sought to assess clinical characteristics and pattern of collateral network involvement associated with development of truncal (systematized) versus diffuse/non-truncal (non-systematized) varicose veins (VVs) in patients undergoing endovascular laser photothermolysis for chronic venous insufficiency (CVI). Secondly, we aimed to assess whether the type of VVs influenced the procedural complications of endovascular laser therapy. A total of 508 patients with hydrostatic VVs of the lower limbs who underwent endovenous laser treatment were included, out of which 84.1% (n=427) had truncal VVs (group 1) and 15.9% (n=81) had diffuse (non-systematized) VVs (group 2). Patients with truncal varices were significantly older (47.50±12.80 vs 43.15±11.75 years, P=0.004) and those with associated connective tissue disorders were more prone to present diffuse VVs (P=0.004). Patients in group 1 presented a significantly higher number of Cockett 1 (P=0.0017), Cockett 2 (P=0.0137), Sherman (P<0.0001), and Hunter (P=0.0011) perforator veins compared to group 2, who presented a higher incidence of Kosinski perforators (P<0.0001). There were no significant differences regarding postoperative complications: thrombophlebitis (P=0.773), local inflammation (P=0.471), pain (P=0.243), paresthesia (P=1.000), or burning sensation (P=0.632). Patients with more advanced CEAP (clinical, etiologic, anatomic, pathophysiologic) classes were older (P<0.0001), more were males (39.05 vs 27.77%, P=0.0084), more were prone to present ulcers (P<0.0001) and local hyperthermia (P=0.019), and presented for endovenous phlebectomy after a longer time from symptom onset. In patients with CVI, systematized VVs were associated with a more severe clinical status and a distinct anatomical pattern of perforators network compared to non-systematized VVs, which is more common in advanced stages.

Resumo em Inglês:

Preeclampsia is a major reason of morbidity and mortality in pregnant women and perinatal fetus. Hence, it is of prime importance that diagnostic markers are defined to predict chances of preeclampsia in pregnant women. It has been previously shown that microRNA (miRNA)-376c expression is decreased in the placenta of preeclampsia patients at term. Even though this decrease was not mimicked in the placenta at the pre-term stage, miR-376c expression was decreased in the plasma of these patients as early as the second trimester. Plasma and placenta specimens were obtained from pregnant women having unifetal gestation undergoing perinatal care between January 2014 and December 2016 (n=49). Early trimester placentas were collected from patients undergoing terminated pregnancies through dilation and curettage procedure. Our results showed that in addition to miR-376c, miR-441 levels were decreased in the placenta of preeclampsia patients, and this decrease occurred both at pre-term and at term. This decrease is also mimicked in the plasma levels at both early and late weeks of pregnancy, highlighting that miR-441 levels can serve as a diagnostic marker of risk of preeclampsia in pregnant women. Overexpression of the miR-441, as well as miR-376c, promoted cell viability, migration, and invasion in the human immortalized cytotrophoblast cell line HTR8/SVneo, indicating that their decrease in pregnant women would result in anomalous apoptosis and functional imbalance resulting in premature abortion and other complications. MiR-441 level can thus potentially serve as diagnostic marker of preeclampsia in pregnant women.

Resumo em Inglês:

Reactive oxygen species (ROS) are highly reactive chemical species that may cause irreversible tissue damage, and play a critical role in cardiovascular diseases. Hydrogen sulfide (H2S) is a gasotransmitter that acts as a ROS scavenger with cardio-protective effects. In this study, we investigated the cytoprotective effect of H2S against H2O2-induced apoptosis in cardiomyocytes. H9c2 rat cardiomyoblasts were treated with H2S (100 μM) 24 h before challenging with H2O2 (100 μM). Apoptosis was then assessed by annexin V and PI, and mitochondrial membrane potential was measured using a fluorescent probe, JC-1. Our results revealed that H2S improved cell viability, reduced the apoptotic rate, and preserved mitochondrial membrane potential. An increased Bcl-2 to Bax ratio was also seen in myocytes treated with H2S after H2O2-induced stress. Our findings indicated a therapeutic potential for H2S in preventing myocyte death following ischemia/reperfusion.

Resumo em Inglês:

The leading cause of death in systemic lupus erythematosus (SLE) patients is infection. The objective of this study was to evaluate the distribution of lymphocyte subsets in untreated SLE patients with infections. This was a cross-sectional study. Data from January 2017 to May 2018 were collected. Flow cytometry was used to measure the peripheral lymphocyte subsets including CD3+T cells, CD4+T cells, CD8+T cells, CD19+B cells, CD3-CD16+CD56NK cells, and CD3+CD16+CD56NKT cells in 25 healthy controls and 52 treatment-naive SLE patients, among whom 13 were complicated with infections. Association between the lymphocyte subsets and infections was further analyzed. SLE patients with infections (n=13) showed a significantly higher incidence rate of fever (84.6 vs 28.2%) and serositis (84.6 vs 23.1%), increased level of erythrocyte sedimentation rate (60.5±30.1 vs 37.4±27.1 mm/h), serum C-reactive protein (CRP) (102.7±94.9 vs 9.4±14.9 mg/L), procalcitonin (PCT) (1.07±0.08 vs 0.16±0.13 μg/L), and lower blood hemoglobin (Hb) (93.0±20.5 vs 110.4±16.0 g/L) level compared with non-infection patients (n=39) (all P<0.05). In comparison with non-infectious SLE patients (387.9±261.6/μL), CD4+T cells count decreased significantly in infectious SLE patients (217.8±150.4/μL) (P<0.05), and it was negatively correlated with infection-related indicators including PCT (r=−0.573, P=0.041) and CRP (r=−0.596, P=0.032) levels. Our findings suggested that abnormalities of peripheral lymphocyte subsets were related to the immune disorder of lupus itself, regardless of immunosuppressive treatment. Monitoring lymphocyte subsets, especially CD4+T cells, may be helpful for identifying the presence of infection in SLE patients.

Resumo em Inglês:

Although normal aging has been related to several cognitive difficulties, other processes have been studied less, such as spatial memory. Our aim was to compare egocentric and allocentric memory in an elderly population using ecological tasks. Twenty-eight cognitively unimpaired participants performed Egocentric and Allocentric Spatial Memory Tasks, as well as Spatial Span from CANTAB, Benton's Judge of Line Orientation test (JoLO), and Montreal Cognitive Assessment test (MoCA). The results revealed that younger participants showed better performance than older participants on both the Egocentric and Allocentric Spatial Memory Tasks, although only the Egocentric test was able to discriminate between younger, middle, and older elderly participants. Learning effect was found in Allocentric Spatial Memory Task in younger and older groups, but not in the middle group. Allocentric and egocentric performance was not related to other visuospatial neuropsychological scores and gender did not influence performance in any task. Egocentric and Allocentric Spatial Memory Tasks may be useful tools in early screening for cognitive decline, as they are able to detect age differences in the cognitive unimpaired elderly population.