Resumo em Inglês:

The mixture of ketamine and xylazine is widely used for the auditory brainstem response (ABR) measurement. Esketamine is twice as potent as ketamine. Our objective was to assess the influence of esketamine in mice undergoing cochlear function measurement including ABR and distortion product otoacoustic emission (DPOAE) measurement. C57Bl/6J mice were treated with an equivalent dose of analgesia and received either a single intraperitoneal (ip) injection of 100 mg/kg ketamine and 25 mg/kg xylazine or 50 mg/kg esketamine and 25 mg/kg xylazine. Hearing thresholds, peak latencies of waves I and V, and DPOAE thresholds were recorded. Time to loss of righting and time to regain righting were also assessed. We found that hearing thresholds, the peak latencies of waves I and V, and DPOAE thresholds were similar between the two groups (all P>0.05). Time to regain righting was significantly shorter in the esketamine group (P<0.001) than in the ketamine group. We concluded that when using equivalent doses of analgesia, esketamine may be an ideal substitute for ketamine during cochlear function test.

Resumo em Inglês:

Continuous positive airway pressure (CPAP) has been used to improve gas exchange and diaphragmatic function, among others benefits. Moreover, it can be used to increase exercise tolerance and positively influence ventilatory function and breathing pattern (BP) during exercise. However, there is no information about the long-term effects of CPAP, as an adjunct to an inpatient cardiac rehabilitation (CR) program, on BP and heart rate variability (HRV) of patients after coronary artery bypass grafting surgery (CABG). Twenty patients were allocated to receive, after randomization, standard inpatient CR without CPAP (control group - CG) or CR with CPAP between 10 to 12 cmH2O (CPAP group - CPG) associated with the exercises. Participants were assessed preoperatively and on the discharge day, in the sitting rest position. Outcome measurements included BP variables, collected by respiratory inductive plethysmography, and HRV, collected by polar precision performance. The CPG presented lower values of percent rib cage inspiratory and expiratory contributions to tidal volume (%RCi and %RCe) at discharge time, compared to CG. No statistical differences between groups were observed for HRV variables and both groups presented lower values of these indices, compared to preoperative ones. In this context, the patients who received CPAP throughout the whole rehabilitation program were discharged with a better BP, which could indicate more synchronized breathing. CPAP did not influence cardiac autonomic modulation in the long term.

Resumo em Inglês:

The present study focused on the scenario of confirmed cases of SARS-CoV-2 infection in the state of Minas Gerais (MG), Brazil, from March 2020 to March 2021. We evaluated the evolution of COVID-19 prevalence and death in one municipality from each of the 14 health macro-regions of MG state. Socio-demographic characteristics and variables related to the municipalities were analyzed. The raw dataset used in this study was freely sourced from the website Brasil.io. From the raw dataset, two time series were extracted: the cumulative confirmed cases of COVID-19 and cumulative death counts, and they were compared to the state data using a nowcasting approach. In order to make time series comparisons possible, all data was normalized per 100,000 inhabitants. When analyzing in light of colored wave code interventions initiated in August 2020 in MG, for the majority of the municipalities, there was an absence of clear influence on prevalence and deaths. The national holidays in the first semester of 2020 had a small impact on the COVID-19 prevalence of the municipalities, but the holidays in the second semester of 2020 and beginning of 2021 caused important impacts on COVID-19 prevalence. The low number of ICU beds in some municipalities contributed to the higher number of deaths. The analysis showed here is expected to contribute to the improvement of decision making of the MG government, as it opened a huge possibility to have the total macro-regions and state data analyzed.

Resumo em Inglês:

This study investigated the acute blockade of endogenous melatonin (MLT) using Luzindole with or without systemic lipopolysaccharide (LPS) challenge and evaluated changes in inflammatory and oxidative stress markers in the mouse jejunum. Luzindole is an MT1/MT2 MLT receptor antagonist. Both receptors occur in the small intestine. Swiss mice were treated with either saline (0.35 mg/kg, ip), Luzindole (0.35 mg/kg, ip), LPS (1.25 mg/kg, ip), or Luzindole+LPS (0.35 and 1.25 mg/kg, ip, respectively). Jejunum samples were evaluated regarding intestinal morphometry, histopathological crypt scoring, and PAS-positive villus goblet cell counting. Inflammatory Iba-1, interleukin (IL)-1β, tumor necrosis factor (TNF)-α, nuclear factor (NF)-kB, myeloperoxidase (MPO), and oxidative stress (NP-SHs, catalase, MDA, nitrate/nitrite) markers were assessed. Mice treated with Luzindole, LPS, and Luzindole+LPS showed villus height shortening. Crypt damage was worse in the LPS group. Luzindole, LPS, and Luzindole+LPS reduced the PAS-goblet cell labeling and increased Iba-1-immunolabelled cells compared to the saline group. Immunoblotting for IL-1β, TNF-α, and NF-kB was greater in the Luzindole group. The LPS-challenged group showed higher MPO activity than the saline and Luzindole groups. Catalase was reduced in the Luzindole and Luzindole+LPS groups compared to saline. The Luzindole group showed an increase in NP-SHs, an effect related to compensatory GSH activity. The acute blockade of endogenous MLT with Luzindole induced early changes in inflammatory markers with altered intestinal morphology. The other non-detectable deleterious effects of Luzindole may be balanced by the unopposed direct action of MLT in immune cells bypassing the MT1/MT2 receptors.

Resumo em Inglês:

This study aimed to investigate the diagnostic value of heparin-binding protein (HBP) in the cerebrospinal fluid of children with purulent meningitis (PM). This study included 118 children with PM diagnosed at our hospital from January 2018 to January 2020, 110 children with viral meningitis (VM) and 80 children with suspected meningitis who were ruled out by cerebrospinal fluid (CSF) analysis during the same period. HBP and white blood cell (WBC) count in the CSF, and inflammatory factors, including C-reactive protein (CRP), tumor necrosis factor (TNF)-α, and procalcitonin (PCT), were measured. Receiver-operator characteristic curves were used to analyze the predictive value of HBP, CRP, PCT, and TNF-α levels in the diagnosis of PM by CSF analysis. HBP levels in the CSF of children with PM were higher, while the CRP and serum PCT and TNF-α levels were elevated in all groups (P<0.05). In addition, HBP levels in the CSF were more accurate for the diagnosis of PM than traditional diagnostic indexes. HBP levels in the CSF can be used as an important reference for early diagnosis of PM.

Resumo em Inglês:

Diabetes mellitus is associated with neural and micro- and macrovascular complications. Therapeutic options for these complications are limited and the delivery of mesenchymal stem cells into lesions have been reported to improve the healing process. In this work, the effects of the administration of a lineage of human bone marrow mesenchymal stem cells immortalized by the expression of telomerase (hBMSC-TERT) as a potential therapeutic tool for wound healing in diabetic rats were investigated. This is the first description of the use of these cells in diabetic wounds. Dorsal cutaneous lesions were made in streptozotocin-induced diabetic rats and hBMSC-TERT were subcutaneously administered around the lesions. The healing process was evaluated macroscopically, histologically, and by birefringence analysis. Diabetic wounded rats infused with hBMSC-TERT (DM-TERT group) and the non-diabetic wounded rats not infused with hBMSC-TERT (CW group) had very similar patterns of fibroblastic response and collagen proliferation indicating improvement of wound healing. The result obtained by birefringence analysis was in accordance with that obtained by the histological analysis. The results indicated that local administration of hBMSC-TERT in diabetic wounds improved the wound healing process and may become a therapeutic option for wounds in individuals with diabetes.

Resumo em Inglês:

There are many medications available to treat spasticity, but the tolerability of medications is the main issue for choosing the best treatment. The objectives of this study were to compare the efficacy and adverse effects of tolperisone compared to baclofen among patients with spasticity associated with spinal cord injury. Patients received baclofen plus physical therapy (BAF+PT, n=135) or tolperisone plus physical therapy (TOL+PT, n=116), or physical therapy alone (PT, n=180). The modified Ashworth scale score, the modified Medical Research Council score, the Barthel Index score, and the Disability Assessment scale score were improved (P<0.05 for all) in all the patients at the end of 6 weeks compared to before interventions. After 6 weeks, the overall coefficient of efficacy of the intervention(s) in the BAF+PT, TOL+PT, and PT groups were 1.15, 0.45, and 0.05, respectively. The patients of the BAF+PT group reported asthenia, drowsiness, and sleepiness and those of the TOL+PT group reported dyspepsia and epigastric pain as adverse effects. When comparing drug interventions to physical therapy alone, both baclofen plus physical therapy and tolperisone plus physical therapy played a significant role in the improvement of daily activities of patients. Nonetheless, baclofen plus physical therapy was tentatively effective. Tolperisone plus physical therapy was slightly effective. In addition, baclofen caused adverse effects related to the sedative manifestation (Level of Evidence: III; Technical Efficacy Stage: 4).

Resumo em Inglês:

Acute kidney injury (AKI) is a common complication in seriously ill patients, while renal ischemia-reperfusion (I/R) injury is the most frequent event in this oxidative renal injury. N-acetylcysteine (NAC) is a small molecule containing a thiol group that has antioxidant properties, promoting detoxification and acting directly as a free radical scavenger. In this study, the protective effect of NAC was investigated in short-term (30 min) and long-term (45 min) ischemic AKI. This was achieved via clamping of the renal artery for 30 or 45 min in Wistar rats to induce I/R injury. AKI worsened with a longer period of ischemia (45 compared to 30 min) due to probable irreversible damage. Preconditioning with NAC in short-term ischemia improved renal blood flow and increased creatinine clearance by reducing oxidative metabolites and increasing antioxidant capacity. Otherwise, NAC did not change these parameters in the long-term ischemia. Therefore, this study demonstrated that the period of ischemia determines the severity of the AKI, and NAC presented antioxidant effects in short-term ischemia but not in long-term ischemia, confirming that there is a possible therapeutic window for its renoprotective effect.

Resumo em Inglês:

Immune-mediated inflammation plays a key role in the pathology of abdominal aortic aneurysm (AAA). We aimed to use a computational approach to profile the immune infiltration patterns and related core genes in AAA samples based on the overexpression of gene signatures. The microarray datasets of AAA and normal abdominal tissues were acquired from gene expression omnibus (GEO) database. We evaluated the composition of immune infiltrates through microenvironment cell populations (MCP)-counter. Weighted gene correlation network analysis (WGCNA) was employed to construct the co-expression network and extract gene information in the most relevant module. Functional and pathway enrichment analysis was performed and immune infiltration related core genes were screened. AAA tissues had a higher level of infiltration by cytotoxic lymphocytes, NK cells, T cells, fibroblasts, myeloid dendritic cells, and neutrophils than normal aorta. The red module was strongly correlated with the infiltrating levels of T cells and cytotoxic lymphocytes. Gene ontology (GO) and pathway analyses revealed that genes in the most relevant module were mainly enriched in T cell activation, regulation of lymphocyte activation, cytokine-cytokine receptor interaction, and chemokine signaling pathway, etc. The expression of GZMK, CCL5, GZMA, CD2, and EOMES showed significant correlations with cytotoxic lymphocytes, while CD247, CD2, CD6, RASGRP1, and CD48 expression were positively associated with T cell infiltration. In conclusion, we comprehensively analyzed profiles of infiltrated immune cells in AAA tissues and their associated marker genes. Our data may provide a novel clue to indicate the underlying molecular mechanisms of AAA formation in terms of immune infiltration.

Resumo em Inglês:

Cervical cancer (CC) is the most common malignant tumor in females. Although persistent high-risk human papillomavirus (HPV) infection is a leading factor that causes CC, few women with HPV infection develop CC. Therefore, many mechanisms remain to be explored, such as aberrant expression of oncogenes and tumor suppressor genes. To identify promising prognostic factors and interpret the relevant mechanisms of CC, the RNA sequencing profile of CC was downloaded from the Cancer Genome Atlas and the Gene Expression Omnibus databases. The GSE63514 dataset was analyzed, and differentially expressed genes (DEGs) were obtained by weighted coexpression network analysis and the edgeR package in R. Fifty-three shared genes were mainly enriched in nuclear chromosome segregation and DNA replication signaling pathways. Through a protein-protein interaction network and prognosis analysis, the kinesin family member 14 (KIF14) hub gene was extracted from the set of 53 shared genes, which was overexpressed and associated with poor overall survival (OS) and disease-free survival (DFS) of CC patients. Mechanistically, gene set enrichment analysis showed that KIF14 was mainly enriched in the glycolysis/gluconeogenesis signaling pathway and DNA replication signaling pathway, especially in the cell cycle signaling pathway. RT-PCR and the Human Protein Atlas database confirmed that these genes were significantly increased in CC samples. Therefore, our findings indicated the biological function of KIF14 in cervical cancer and provided new ideas for CC diagnosis and therapies.

Resumo em Inglês:

This study aimed to explore gene expression profiles that drive malignancy from low- to high-grade head and neck carcinomas (HNC), as well as to analyze their correlations with survival. Gene expressions and clinical data of HNC were downloaded from the Gene Expression Omnibus (GEO) repository. The significantly differential genes (SDGs) between low- and high-grade HNC were screened. Cox regressions were performed to identify prognostic SDGs of progression-free survival (PFS) and disease-specific survival (DSS). The genes were experimentally validated by RT-PCR in clinical tissue specimens. Thirty-five SDGs were identified in 47 low-grade and 30 high-grade HNC samples. Cox regression analyses showed that CXCL14, SLC44A1, and UBD were significantly associated with DSS, and PPP2R2C and SLC44A1 were associated with PFS. Patients were grouped into high-risk or low-risk groups for prognosis based on gene signatures. High-risk patients had significantly shorter DSS and PFS than low-risk patients (P=0.033 and P=0.010, respectively). Multivariate Cox regression showed HPV (P=0.033), lymph node status (P=0.032), and residual status (P<0.044) were independent risk factors for PFS. ROC curves showed the risk score had better efficacy to predict survival both for DSS and PFS (AUC=0.858 and AUC=0.901, respectively). The results showed CXCL14 and SLC44A1 were significantly overexpressed in the low-grade HNC tissues and the UBD were overexpressed in the high-grade HNC tissues. Our results suggested that SDGs had different expression profiles between the low-grade and high-grade HNC, and these genes may serve as prognostic biomarkers to predict survival.

Resumo em Inglês:

Cervical cancer (CC) patients have a poor prognosis due to the high recurrence rate. However, there are still no effective molecular signatures to predict the recurrence and survival rates for CC patients. Here, we aimed to identify a novel signature based on three types of RNAs [messenger RNA (mRNAs), microRNA (miRNAs), and long non-coding RNAs (lncRNAs)]. A total of 763 differentially expressed mRNAs (DEMs), 46 lncRNAs (DELs), and 22 miRNAs (DEMis) were identified between recurrent and non-recurrent CC patients using the datasets collected from the Gene Expression Omnibus (GSE44001; training) and The Cancer Genome Atlas (RNA- and miRNA-sequencing; testing) databases. A competing endogenous RNA network was constructed based on 23 DELs, 15 DEMis, and 426 DEMs, in which 15 DELs, 13 DEMis, and 390 DEMs were significantly associated with disease-free survival (DFS). A prognostic signature, containing two DELs (CD27-AS1, LINC00683), three DEMis (hsa-miR-146b, hsa-miR-1238, hsa-miR-4648), and seven DEMs (ARMC7, ATRX, FBLN5, GHR, MYLIP, OXCT1, RAB39A), was developed after LASSO analysis. The built risk score could effectively separate the recurrence rate and DFS of patients in the high- and low-risk groups. The accuracy of this risk score model for DFS prediction was better than that of the FIGO (International Federation of Gynecology and Obstetrics) staging (the area under receiver operating characteristic curve: training, 0.954 vs 0.501; testing, 0.882 vs 0.656; and C-index: training, 0.855 vs 0.539; testing, 0.711 vs 0.508). In conclusion, the high predictive accuracy of our signature for DFS indicated its potential clinical application value for CC patients.

Resumo em Inglês:

Dietary factors may influence the process of atherosclerosis and coronary artery calcification (CAC). This study assessed CAC and its association with dietary intake in asymptomatic men. We evaluated 150 asymptomatic men with mean age of 58.2±5.3 years. The dietary intake was assessed by the Food Consumption Register method. CAC was measured through multidetector computed tomography (MDCT) and assessed in accordance with the Agatston score. Modified Poisson regression model was used to estimate the effects of intake of different nutrients that are prevalent in moderate/severe CAC, adjusted for calorie intake and CAC risk factors by means of prevalence ratios and 95% confidence intervals [95%CI]. An association was found between the intake of some nutrients and moderate/severe CAC. Lower carbohydrate intake (P=0.021) and higher lipid intake (P=0.006) were associated with moderate/severe CAC. After adjustment, the nutrients associated with the prevalence of moderate/severe CAC were carbohydrates (P=0.040), lipids (P=0.005), and saturated fatty acids (SFA) (P=0.013). A 1% increase in lipids and SFA intake caused an increase of 4% [95%CI: 1-7%] and 8% [95%CI: 2-14%] in the prevalence of moderate/severe CAC, respectively. A 1% increase of carbohydrate intake led to a 2% decrease in the likelihood of moderate/severe CAC [95%CI: 1-4%]. These conclusions showed that the higher intake of total lipids and SFA was associated with higher CAC scores, whereas higher carbohydrate intake was associated with lower CAC scores in asymptomatic men.

Resumo em Inglês:

Sedentary time is associated with increased obesity in police officers. Caffeine intake may reduce sedentary time but it has not been extensively investigated. In the present study, the effect of caffeine ingestion on sedentary time was investigated in obese police officers. Fourteen obese police officers ingested either 5 mg/kg of caffeine or cellulose (placebo) for six days. Information on inactivity time, time spent with physical activities, self-reported perception of tiredness, and physical activity disposition was obtained daily during the intervention period. Sedentary and physical activity times were divided into two intraday periods (T1: 08:00 am-02:00 pm and T2: 02:00 pm-08:00 pm). Caffeine intake decreased the sedentary time in both T1 (79.2±2.2%) and T2 (79.1±2.5%), when compared with T2 of the placebo condition (81.1±3.6%, P<0.05). Caffeine intake also increased the time spent on light physical activities in T1 and T2 (17±2 and 18±2%), when compared with T2 of the placebo condition (16±3%, P<0.05). In addition, sedentary time increased and light physical activity time decreased from T1 to T2 in the placebo (P<0.001) but not in the caffeine condition (P=0.81). Caffeine intake had no effect on tiredness (P>0.05), but it increased the self-reported physical activity disposition compared to the placebo condition (4.5±2.7 vs 3.2±2.3 units, P<0.05). Caffeine intake reduced the sedentary time and increased the time spent on light physical activities of obese police officers, which seems to be related to a higher disposition for the practice of physical activity.

Resumo em Inglês:

Maternal anxiety symptoms in the perinatal period might have long-term health effects on both the mother and the developing child. Valerian is a phytotherapeutic agent that is widely used for the treatment of anxiety. This study investigated the effects of valerian treatment in postpartum rats on maternal care, toxicity, and milk composition. Postnatal development, memory, and anxiety behavior in the offspring were also assessed. Postpartum Wistar rats received the valerian (500, 1000, or 2000 mg·kg–1·day–1) by oral gavage. Clinical and biochemical toxicity was evaluated with commercial kits. Maternal behavior was observed daily. Milk composition was analyzed by colorimetric methods. Physical and neuromotor tests were used to analyze postnatal development. Anxiolytic activity was assessed by the elevated plus maze, and memory was evaluated by the step-down inhibitory avoidance task. Maternal toxicity and care behavior were not altered by the treatment, while only the highest dose promoted a significant increase of lactose, and the doses 1000 and 2000 mg·kg–1·day–1 promoted a reduction of protein contents in milk. Postnatal development was similar in all offspring. Adult offspring did not display altered anxiety behavior, while long-term memory was impaired in the female adult offspring by maternal treatment with 1000 mg·kg–1·day–1. These results suggested that high doses of valerian had significant effects on important maternal milk components and can cause long-term alterations of offspring memory; thus, treatment with high doses of valerian is not safe for breastfeeding Wistar rat mothers.

Resumo em Inglês:

Current understanding of the genetic factors contributing to the etiology of non-syndromic craniosynostosis (NSC) remains scarce. The present work investigated the presence of variants in ALX4, EFNA4, and TWIST1 genes in children with NSC to verify if variants within these genes may contribute to the occurrence of these abnormal phenotypes. A total of 101 children (aged 45.07±40.94 months) with NSC participated in this cross-sectional study. Parents and siblings of the probands were invited to participate. Medical and family history of craniosynostosis were documented. Biological samples were collected to obtain genomic DNA. Coding exons of human TWIST1, ALX4, and EFNA4 genes were amplified by polymerase chain reaction and Sanger sequenced. Five missense variants were identified in ALX4 in children with bilateral coronal, sagittal, and metopic synostosis. A de novo ALX4 variant, c.799G>A: p.Ala267Thr, was identified in a proband with sagittal synostosis. Three missense variants were identified in the EFNA4 gene in children with metopic and sagittal synostosis. A TWIST1 variant occurred in a child with unilateral coronal synostosis. Variants were predicted to be among the 0.1% (TWIST1, c.380C>A: p. Ala127Glu) and 1% (ALX4, c.769C>T: p.Arg257Cys, c.799G>A: p.Ala267Thr, c.929G>A: p.Gly310Asp; EFNA4, c.178C>T: p.His60Tyr, C.283A>G: p.Lys95Glu, c.349C>A: Pro117Thr) most deleterious variants in the human genome. With the exception of ALX4, c.799G>A: p.Ala267Thr, all other variants were present in at least one non-affected family member, suggesting incomplete penetrance. Thus, these variants may contribute to the development of craniosynostosis, and should not be discarded as potential candidate genes in the diagnosis of this condition.