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Myelodysplastic Neoplasm (MDS) is a cancer associated with aging, often leading to acute myeloid leukemia (AML). One of its hallmarks is hypermethylation, particularly in genes responsible for DNA repair. This study aimed to evaluate the methylation and mutation status of DNA repair genes (single-strand - XPA, XPC, XPG, CSA, CSB and double-strand - ATM, BRCA1, BRCA2, LIG4, RAD51) in MDS across three patient cohorts (Cohort A-56, Cohort B-100, Cohort C-76), using methods like pyrosequencing, real-time PCR, immunohistochemistry, and mutation screening. Results showed that XPA had higher methylation in low-risk MDS compared to high-risk MDS. For double-strand repair genes, ATM displayed higher methylation in patients who transformed to AML (p = 0.016). ATM gene expression was downregulated in MDS compared to controls (p = 0.042). When patients were classified according to the WHO 2022 guidelines, ATM expression progressively decreased from low-risk subtypes (e.g., Hypoplastic MDS) to high-risk MDS and AML. Patients who transformed to AML had a higher 5mC/5hmC ratio compared to those who didn't (p = 0.045). Additionally, poor cytogenetic risk patients had higher tissue methylation scores than those with good risk (p = 0.035). Analysis using the cBioPortal platform identified ATM as the most frequently mutated DNA repair gene, with various mutations, such as frameshift and missense, most of which were classified as oncogenic. The findings suggest that ATM is frequently silenced or downregulated in MDS due to methylation or mutations, contributing to the progression to AML. This highlights ATM's potential role in the disease's advancement and as a target for future therapeutic strategies., Competing Interests: Declaration of Competing Interest The authors declare that they have no competing interests., (Copyright © 2025 Elsevier B.V. All rights reserved.)

Loop-mediated isothermal amplification (LAMP) is a highly effective molecular diagnostic technique, particularly advantageous for point-of-care (POC) settings. In recent years, LAMP has expanded to include various adaptations such as DARQ-LAMP, QUASR, FLOS-LAMP, displacement probes and molecular beacons. These methods enable multiplex detection of multiple targets in a single reaction, enhancing cost-effectiveness and diagnostic efficiency. Consequently, LAMP has gained significant traction in diagnosing diverse viruses, notably during the COVID-19 pandemic. However, its application for detecting Herpesviridae remains relatively unexplored. This group of viruses is of particular interest due to their latency and potential reactivation, crucial for immunocompromised patients, including organ and hematopoietic stem cell transplant recipients. This review highlights recent advancements in LAMP for virus diagnosis and explores current research trends and future prospects, emphasizing the detection challenges posed by Herpesviridae.

Cellular compartmentalization, achieved through membrane-based compartments, is a fundamental aspect of cell biology that contributes to the evolutionary success of cells. While organelles have traditionally been the focus of research, membrane-less organelles (MLOs) are emerging as critical players, exhibiting distinct morphological features and unique molecular compositions. Recent research highlights the pivotal role of long noncoding RNAs (lncRNAs) in MLOs and their involvement in various cellular processes across different organisms. In the context of cancer, dysregulation of MLO formation, influenced by altered lncRNA expression, impacts chromatin organization, oncogenic transcription, signaling pathways, and telomere lengthening. This review synthesizes the current understanding of lncRNA composition within MLOs, delineating their functions and exploring how their dysregulation contributes to human cancers. Environmental challenges in tumorigenesis, such as nutrient deprivation and hypoxia, induce stress granules, promoting cancer cell survival and progression. Advancements in biochemical techniques, particularly single RNA imaging methods, offer valuable tools for studying RNA functions within live cells. However, detecting low-abundance lncRNAs remains challenging due to their limited expression levels. The correlation between lncRNA expression and pathological conditions, particularly cancer, should be explored, emphasizing the importance of single-cell studies for precise biomarker identification and the development of personalized therapeutic strategies. This article is categorized under: RNA Export and Localization > RNA Localization RNA in Disease and Development > RNA in Disease RNA Interactions with Proteins and Other Molecules > RNA-Protein Complexes., (© 2024 Wiley Periodicals LLC.)

Corticobasal syndrome (CBS) is a rare cause of dementia and comprises varied combinations of subcortical signs (akinetic-rigid parkinsonism, dystonia, or myoclonus) with cortical signs (apraxia, alien hand or cortical sensory deficit), usually asymmetric. We aimed to report and compare the clinical and neuroimaging presentation of two patients diagnosed with CBS. While case 1 had severe non-fluent aphasia associated with mild apraxia and limb rigidity, case 2 had a more posterior cognitive impairment, with a different language pattern associated with marked visuospatial errors and hemineglect. FDG PET played a significant role in diagnosis, suggesting, in the first case, corticobasal degeneration and, in the second, Alzheimer's disease pattern. CBS has been widely studied with the advent of new in vivo methods such as brain FDG PET. Studies that deepen the phenotypic and biomarker heterogeneity of CBS will be of great importance for better classification, prognosis, and treatment of the condition., Competing Interests: Disclosure: The authors report no conflicts of interest.

Purpose: The present study aimed to assess whether there was an increase in physical aggression in women treated in Belo Horizonte, Minas Gerais, through the mandatory quarantine., Methods: Data from a cross-sectional study were collected and analyzed, from March 1 to December 31, 2020. Additionally, data from the same period the previous year were collected for comparison., Results: Of the etiologies reviewed for 2020, physical aggression had the highest percentage increase (+ 4.9%) and was the only etiology that showed a significant difference (p = 0.045). The mean age of the included patients was 34.05 years in 2019 and 33.97 in 2020, and most of the women had facial fractures, with nasal fractures being the most frequent, followed by jaw fractures. There was a significant increase (p = 0.34) in the conservative treatment of fractures from 2019 (48.6%) to 2020 (71.7%) and a minor (p = 0.088) increase in aggression toward intimate partners (2019, 40.9%; 2020, 63.9%)., Conclusion: Physical aggression against women increased during the period of mandatory social isolation that resulted from the COVID-19 pandemic. Health professionals, including emergency services professionals, must be trained to identify victims and refer them to specialized care., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

This study investigated the prevalence and the potential risk factors for anxiety and depression among physiotherapists during the pandemic. Physiotherapists answered a web-based questionnaire including 1) sociodemographic, professional and clinical information; 2) psychosocial demands; and 3) two validated questionnaires to measure anxiety and depression. Binary logistic regression identified the risk factors by means of odds ratio (OR) and 95% confidence interval (CI). In 417 participants, there was a high prevalence of anxiety (48.2%) and depression (53.0%). The risk factors for anxiety were female sex (OR 2.07; 95%CI 1.01-4.24), worsening in sleep patterns (OR 3.78; 95%CI 1.92-7.44), moderate (OR 2.24; 95%CI 1.00-5.00) and extreme concern about financial issues (OR 3.47; 95%CI 1.57-7.65), and extreme loneliness (OR 3.47; 95%CI 1.71-7.07). The risk factors for depression were female sex (OR 2.16; 95%CI 1.03-4.55), low family income (OR 2.43; 95%CI 1.21-4.89), worsening in sleep patterns (OR 5.97; 95%CI 3.02-11.82), extreme concern about financial issues (OR 2.61; 95%CI 1.15-5.94), and extreme loneliness (OR 4.38; 95%CI 2.00-9.63). This study found a high prevalence of anxiety and depression in the studied population and identified risk factors for both.

As immune checkpoint inhibitors (ICI) emerge as a paradigm-shifting treatment option for patients with advanced or metastatic cancer, there is a growing demand for biomarkers that can distinguish which patients are likely to benefit. In the case of triple-negative breast cancer (TNBC), characterized by a lack of therapeutic targets, pembrolizumab approval for high-risk early-stage disease occurred regardless of PD-L1 status, which keeps the condition in a biomarker limbus. In this review, we highlight the participation of long non-coding RNAs (lncRNAs) in the regulation of the PD-1/PD-L1 pathway, as well as in the definition of prognostic immune-related signatures in many types of tumors, aiming to shed light on molecules that deserve further investigation for a potential role as biomarkers. We also conducted a bioinformatic analysis to investigate lncRNAs already investigated in PD-1/PDL-1 pathways in other cancer types, considering the TNBC molecular context. In this sense, from the generated data, we evidence here two lncRNAs, UCA1 and HCP5, which have not yet been identified in the context of the tumoral immune response in breast cancer. These candidates can be further explored to verify their use as biomarkers for ICI response. In this article, we present an updated review regarding the use of lncRNA as biomarkers of response to ICI, highlighting the versatility of using these molecules.

Long noncoding RNAs (lncRNAs) are a class of non-coding RNAs that contain more than 200 nucleotides and exhibit a versatile regulatory capacity. Genomic alterations in lncRNAs have already been investigated in several complex diseases, including breast cancer (BC). BC is a highly heterogeneous disease and is the most prevalent cancer type among women worldwide. Single nucleotide polymorphisms (SNPs) in lncRNA regions appear to have an important role in BC susceptibility; however, little is known about lncRNA-SNPs in the Brazilian population. This study used Brazilian tumor samples to identify lncRNA-SNPs with a biological role in BC development. We applied a bioinformatic approach intersecting lncRNAs that are differentially expressed in BC tumor samples using The Cancer Genome Atlas (TCGA) cohort data and looked for lncRNAs with SNPs associated with BC in the Genome Wide Association Studies (GWAS) catalog. We highlight four lncRNA-SNPs-rs3803662, rs4415084, rs4784227, and rs7716600-which were genotyped in Brazilian BC samples in a case-control study. The SNPs rs4415084 and rs7716600 were associated with BC development at higher risk. These SNPs were also associated with progesterone status and lymph node status, respectively. The rs3803662/rs4784227 haplotype GT was associated with BC risk. These genomic alterations were also evaluated in light of the lncRNA's secondary structure and gain/loss of miRNA binding sites to better understand its biological functions. We emphasize that our bioinformatics approach could find lncRNA-SNPs with a potential biological role in BC development and that lncRNA-SNPs should be more deeply investigated in a highly heterogeneous disease population.

Background: The novel coronavirus disease (COVID-19) may cause vascular (e.g., endothelial dysfunction, and arterial stiffness), cardiac, autonomic (e.g., heart rate variability [HRV]), and systemic inflammatory response via direct viral attack, hypoxia-induced injury, or immunological dysregulation, especially in those patients with pre-existing cardiovascular diseases (CVD). However, to date, no study has shown prevalence of endothelial dysfunction, arterial stiffness and heart rate variability assessed by bedside peripheral arterial tonometry in patients with previous CVD hospitalized in the acute phase of COVID-19., Objective: This study aimed to assess the prevalence of endothelial dysfunction, arterial stiffness, and altered HRV in patients with CVD hospitalized due to COVID-19., Methods: This cross-sectional study was conducted from July 2020 to February 2021. Included male and female adult patients aged 40 to 60 years with previous CVD and diagnosed with COVID-19. Anthropometric data, comorbidities, and blood tests were analyzed. Endothelial function, arterial stiffness, and HRV were assessed using peripheral arterial tonometry (PAT), and the statistical significance was set at 5%., Results: Fourteen (51.8%) patients presented endothelial dysfunction (reactive hyperemia index = 1.2 ± 0.3) and enhancement in the high-frequency component of HRV (p < 0.05). There was a high prevalence of endothelial dysfunction, especially in patients with chronic heart failure (10 (71.4%)). Patients with preserved endothelial function showed a high augmentation index normalized to a heart rate of 75 bpm (p < 0.01), suggesting arterial stiffness., Conclusion: Patients with CVD hospitalized due to COVID-19 presented endothelial dysfunction assessed using PAT, which could be used as a biomarker for arterial stiffness and altered HRV. The possibility of detecting vascular and autonomic changes during phase II of COVID-19 may help to prevent possible long-term complications., Competing Interests: Conflict of Interest None, (Copyright © 2023 Elsevier Inc. All rights reserved.)

Objective: To evaluate the performance of 18F-fluorodeoxyglucose positron emission tomography ( 18 F-FDG PET/CT) radiomic features to predict overall survival (OS) in patients with locally advanced uterine cervical carcinoma., Methods: Longitudinal and retrospective study that evaluated 50 patients with cervical epidermoid carcinoma (clinical stage IB2 to IVA according to FIGO). Segmentation of the 18F-FDG PET/CT tumors was performed using the LIFEx software, generating the radiomic features. We used the Mann-Whitney test to select radiomic features associated with the clinical outcome (death), excluding the features highly correlated with each other with Spearman correlation. Subsequently, ROC curves and a Kaplan-Meier analysis were performed. A p -value < 0.05 were considered significant., Results: The median follow-up was 23.5 months and longer than 24 months in all surviving patients. Independent predictors for OS were found-SUVpeak with an AUC of 0.74, sensitivity of 77.8%, and specificity of 72.7% ( p = 0.006); and the textural feature gray-level run-length matrix GLRLM&#95;LRLGE, with AUC of 0.74, sensitivity of 72.2%, and specificity of 81.8% ( p = 0.005). When we used the derived cut-off points from these ROC curves (12.76 for SUVpeak and 0.001 for GLRLM&#95;LRLGE) in a Kaplan-Meier analysis, we can see two different groups (one with an overall survival probability of approximately 90% and the other with 30%). These biomarkers are independent of FIGO staging., Conclusion: By radiomic 18 F-FDG PET/CT data analysis, SUVpeak and GLRLM&#95;LRLGE textural feature presented the best performance to predict OS in patients with cervical cancer undergoing chemo-radiotherapy and brachytherapy., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Alencar, Machado, Mourato, Oliveira, Moraes, Mattos Junior, Chang, Azevedo and Brandão.)

Purpose: Silveira et al (2020) described a new device that aims to facilitate submental intubation. This study aimed to verify the clinical complications from using this new device for submental endotracheal compared to the conventional technique., Material and Methods: Patients who underwent submental intubation with the orotracheal tube transposition device were compared to those who underwent the conventional technique in a prospective cohort study. The primary predictor variable was intubation technique: conventional versus device-assisted. The primary outcome was total complications (all complications trans and postoperative, were recorded). Secondary variables were 1) age, 2) sex, 3) etiology, 4) race/ethnicity, 5) fracture types, and 6) intubation procedure time. The data were analyzed using descriptive and inferential statistics. Differences were considered statistically significant at P < .05., Results: Forty-two cases are described, including 24 cases with the device and 18 cases using the conventional technique. The mean age was 30.5 ± 11.228 years. The majority of patients were of male sex (88%), non-white (64%), and victims of motorcycle accidents (33%). The mean time to perform submental intubation was 9.9 minutes (±2.1293). Nine complications were recorded, including 2 intraoperative (2 tube dislocations) and 7 postoperative (5 unesthetic scars, one localized hematoma, and one skin infection). The technique used did not affect the time to submental intubation (P = .610). There was no association between technique and occurrence of intraoperative (P = .679; RR = 0.75; confidence interval [CI], 0.05-11.2), postoperative (P = .656; RR = 1.000; CI, 0.255-3.922), or total complications (P = .602; RR = 0.938; CI, 0.293-3.003)., Conclusion: The new device proposed seems to be a good option with similar complication rates as compared to conventional submental intubation., (Copyright © 2022 American Association of Oral and Maxillofacial Surgeons. Published by Elsevier Inc. All rights reserved.)

Objective: To investigate vascular and perivascular abnormalities in the carotid arteries using ultrasound, as well as to evaluate their association with mortality and clinical variables in hospitalized patients with coronavirus disease 2019 (COVID-19)., Materials and Methods: This was a prospective study in which 53 hospitalized patients with severe COVID-19 were evaluated and underwent carotid ultrasound. We documented the carotid ultrasound findings in these patients. Clinical, demographic, laboratory, and imaging features were analyzed and compared by statistical analysis to detect correlations between them., Results: Carotid ultrasound demonstrated luminal surface irregularity in 29 patients (55%), carotid plaques in 30 (57%), perivascular infiltration in four (8%), and increased intima-media thickness (IMT) in 31 (58%). Of the 31 patients with increased IMT, 19 (61%) died, and the association between increased IMT and COVID-19-related mortality was significant ( p = 0.03). Logistic regression showed that the risk of death was 85% in patients who had increased IMT in combination with acute kidney injury at admission or a history of chronic kidney disease ( p < 0.05)., Conclusion: In hospitalized patients with severe COVID-19, carotid ultrasound can show increased IMT, luminal surface irregularity, carotid plaques, and perivascular infiltrates. The combination of increased IMT and kidney damage appears to increase the risk of death in such patients.

Pregnancy in Sickle Cell Disease (SCD) women is associated to increased risk of clinical and obstetrical complications. Placentas from SCD pregnancies can present increased abnormal findings, which may lead to placental insufficiency, favoring adverse perinatal outcome. These placental abnormalities are well known and reported, however little is known about the molecular mechanisms, such as epigenetics. Thus, our aim was to evaluate the DNA methylation profile in placentas from women with SCD (HbSS and HbSC genotypes), compared to uncomplicated controls (HbAA). We included in this study 11 pregnant women with HbSS, 11 with HbSC and 21 with HbAA genotypes. Illumina Methylation EPIC BeadChip was used to assess the whole placental DNA methylation. Pyrosequencing was used for array data validation and qRT-PCR was applied for gene expression analysis. Our results showed high frequency of hypermethylated CpGs sites in HbSS and HbSC groups with 73.5% and 76.2% respectively, when compared with the control group. Differentially methylated regions (DMRs) also showed an increased hypermethylation status for the HbSS (89%) and HbSC (86%) groups, when compared with the control group methylation data. DMRs were selected for methylation validation (4 DMRs-HbSS and 3 DMRs the HbSC groups) and after analyses three were validated in the HbSS group, and none in the HbSC group. The gene expression analysis showed differential expression for the PTGFR (-2.97-fold) and GPR56 (3.0-fold) genes in the HbSS group, and for the SPOCK1 (-2.40-fold) and ADCY4 (1.80-fold) genes in the HbSC group. Taken together, these data strongly suggest that SCD (HbSS and HbSC genotypes) can alter placental DNA methylation and lead to gene expression changes. These changes possibly contribute to abnormal placental development and could impact in the clinical course, especially for the fetus, possibly leading to increased risk of abortion, fetal growth restriction (FGR), stillbirth, small for gestational age newborns and prematurity., Competing Interests: The authors have declared that no competing interests exist.

The aim of this present study is to describe a case of a screwdriver implant aspiration removed with flexible bronchoscopy. This study reviewed the current literature and the authors also proposed an airway management algorithm in case of suspected foreign body aspiration during dental procedures. A review of English-language literature of aspiration of objects after clinical dental practice from 1984 to 2021 was performed. The bronchoscopy was the main method for dental items removal. A total of 57 cases from the literature were enrolled in this study. Aspiration of dental crown and prostheses (43.85%) followed by implant material (19.29%) and tooth (15.78%) were the main aspirated items. Prevention is the better way to avoid this type of complication. Early diagnosis facilitates the removal of foreign body and bronchoscopy is considered the treatment of choice for removal of foreign body aspiration. Also, regular professional training in basic life support is required., Competing Interests: Declaration of Competing Interest The authors have no conflicts of interest to declared, (Copyright © 2021 Elsevier Masson SAS. All rights reserved.)

Objective: To determine which Thyroglobulin (Tg) level after levothyroxine (LT 4 ) withdrawal (stimulated thyroglobulin - sTg) measured before radioiodine therapy (RAIT) is able to predict incomplete response to treatment of differentiated thyroid carcinoma (DTC) with greater sensitivity and specificity one year after initial treatment with I 131 ., Methods: A chart review was performed in which 375 patients with DTC treated with RAIT were included. The sTg was measured in all patients prior to treatment with I 131 . Follow up were then performed one year later. Initial sTg levels were associated to DTC outcomes. A receiver operating characteristic (ROC) curve was performed to achieve a sTg level able to predict which patients would have a greater chance of having an incomplete response to RAIT., Results: Incomplete response to treatment was found in 122 patients (32.5%), this group had a mean sTg of 23.2 ng/mL. ROC curve showed that the optimal cut-off sTg level was 4.4 ng/mL. (sensitivity: 72.1%; specificity: 72.3%; accuracy: 72.2%; positive predictive value of 55.7%; and negative predictive value: 84.3%)., Conclusion: sTg pre-ablation is a valuable predictor of DTC incomplete response to treatment one year after RAIT. Levels of 4.4 ng/ml or more showed higher accuracy to predict this outcome., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Using valved holding chambers (VHC) during aerosol therapy has been reported to improve the inhaled dose with various aerosol devices, including vibrating mesh nebulizers. The aim of this study was to quantify the pulmonary deposition of a jet nebulizer (JN) with and without a VHC, and a mesh nebulizer (MN) with a VHC in a randomized cross-over trial with seven healthy consenting adults. Our hypothesis was that the use of a VHC would improve deposition with the JN. Diethylnitriaminopentacetic acid with technetium (DTPA-Tc99m), with the activity of 1 mC with 0.9% saline solution was nebulized. The radiolabeled aerosol was detected by 2D planar scintigraphy after administration. The pulmonary deposition was greater with a JN with a VHC (4.5%) than a JN alone (3.2%; p = 0.005. However, an MN with a VHC (30.0%) was six-fold greater than a JN or JN with a VHC (p < 0.001). The extrapulmonary deposition was higher in the JN group without a VHC than in the other two modalities (p < 0.001). Deposition in the device was greater with a JN + VHC than an MN+/VHC (p < 0.001). Lower residual drug at the end of the dose was detected with an MN than either JN configuration. The exhaled dose was greater with a JN alone than either an MN or JN with VHC (p < 0.001). In conclusion, the addition of the VHC did not substantially improve the efficiency of aerosol lung deposition over a JN alone.

This study aimed to evaluate the stress perception among Brazilian physical therapists (PTs) during COVID-19 pandemic and to identify which psychosocial demands, sociodemographic, professional and clinical factors do associate with the PTs' stress perception. This cross-sectional survey was based on a convenience sample of PTs, who answered a questionnaire about: 1) sociodemographic and professional characteristics, 2) clinical characteristics and information related to COVID-19, 3) psychosocial demands, and 4) 10-item Perceived Stress Scale (PSS-10). Full responses were obtained from 417 PTs. The average PSS-10 score was 19.2 (95% CI 18.5 to 19.9), which was higher than in other Brazilians before COVID-19 and figured among the highest one observed in healthcare workers from different countries during COVID-19 pandemic. After multivariate analysis, PTs' perceived stress remained associated with female sex, younger age, previous diagnosis of depressive or anxiety disorder, worsening in sleep patterns, large reduction in family income, housework, relationship with the partner, concern about close people/family members being infected by SARS-CoV-2, and loneliness.

COVID-19 and obesity are two pandemic diseases that the world is currently facing. Both activate the immune system and mediate inflammation. A sequence of disease phases in patients with severe COVID-19 results in a cytokine storm, which amplifies the subclinical inflammation that already exists in patients with obesity. Pro-inflammatory cytokines and chemotactic factors increase insulin resistance in obesity. Therefore, a greater systemic inflammatory response is establishe, along with an increased risk of thrombotic phenomena and hyperglycemic conditions. These changes further impair pulmonary, cardiac, hepatic, and renal functions, in addition to hindering glycemic control in people with diabetes and pre-diabetes. This review explains the pathophysiological mechanisms of these two pandemic diseases, provides a deeper understanding of this harmful interaction and lists possible therapeutic strategies for this risk group.

The identification of molecular markers in negative surgical margins of oral squamous cell carcinoma (OSCC) might help in identifying residual molecular aberrations, and potentially improve the prediction of prognosis. We performed an Infinium MethylationEPIC BeadChip array on 32 negative surgical margins stratified based on the status of tumor recurrence in order to identify recurrence-specific aberrant DNA methylation (DNAme) markers. We identified 2512 recurrence-associated Differentially Methylated Positions (DMPs) and 392 Differentially Methylated Regions (DMRs) which were enriched in cell signaling and cancer-related pathways. A set of 14-CpG markers was able to discriminate recurrent and non-recurrent cases with high specificity and sensitivity rates (AUC 0.98, p = 3 × 10 -6 ; CI: 0.95-1). A risk score based on the 14-CpG marker panel was applied, with cases classified within higher risk scores exhibiting poorer survival. The results were replicated using tumor-adjacent normal HNSCC samples from The Cancer Genome Atlas (TCGA). We identified residual DNAme aberrations in the negative surgical margins of OSCC patients, which could be informative for patient management by improving therapeutic intervention. This study proposes a novel DNAme-based 14-CpG marker panel as a promising predictor for tumor recurrence, which might contribute to improved decision-making for the personalized treatment of OSCC cases.

Abstract: The pandemic status of the Novel Coronavirus 2019 has affected many countries around the world, due to the high virulence of the SARS-CoV-2, the recommended protocol to prevent infection is social isolation. The purpose of this study was to compare the number of patients admitted and their epidemiological data on a Level 1 Trauma Hospital after the declaration of the pandemic status and the first week of mandatory lockdown, with the same period of time in the last year. This was a retrospective study of medical records from the patients admitted in the Oral and Maxillofacial Surgery of the João XXIII Hospital, between the March 24 and March 31 of 2020 and the same period of the last year. There was a 52.27% decrease in the total number of patients and 76.34% decrease in the total consultations of the service of oral and maxillofacial surgery during the lockdown. All the groups presented a decrease in significance with motor vehicle accidents events, the group 11 to 20 years old presented an increase on the correlation with violence (P = 0.019) and falls (P = 0.002). When comparing both sex with the etiologies, the male one presented an increase in the correlation with violence and falls. The female sex presented correlations only with the minor causes. No valid significance was observed when comparing females with violence events. The lockdown is an effective way to reduce the transmission of the COVID-19, the hospital usage and occupation., Competing Interests: The authors report no conflicts of interest., (Copyright © 2020 by Mutaz B. Habal, MD.)

The severe form of COVID-19 is marked by an abnormal and exacerbated immunological host response favoring to a poor outcome in a significant number of patients, especially those with obesity, diabetes, hypertension, and atherosclerosis. The chronic inflammatory process found in these cardiometabolic comorbidities is marked by the overexpression of pro-inflammatory cytokines such as interleukin-6 (IL-6) and tumoral necrosis factor-alpha (TNF-α), which are products of the Toll-Like receptors 4 (TLR4) pathway. The SARS-CoV-2 initially infects cells in the upper respiratory tract and, in some patients, spread very quickly, needing respiratory support and systemically, causing collateral damage in tissues. We hypothesize that this happens because the SARS-CoV-2 spike protein interacts strongly with TLR4, causing an intensely exacerbated immune response in the host's lungs, culminating with the cytokine storm, accumulating secretions and hindering blood oxygenation, along with the immune system attacks the body, leading to multiple organ failure., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Severe acute respiratory syndrome coronavirus 2 infection is capable of affecting several organs. Direct viral toxicity, pro-inflammatory and pro-thrombotic induction, endothelial damage, immune imbalance, and dysregulation of the renin-angiotensin-aldosterone system are the mechanisms underlying the viral potential of multiple organ damage. The impairment of four organs stands out among severe patients: lung, heart, kidney, and endothelium. The nuclear medicine field holds accurate and safe exam techniques, such as positron emission tomography-computed tomography and scintigraphy, that allow the anatomophysiological study of the majority of human organ systems. By choosing the most appropriate method and radiopharmaceutical, analyzing the presence of inflammation, fibrosis, changes in perfusion, and function of desired organs is possible. Therefore, its use in the monitoring of patients with coronavirus disease 2019 becomes relevant, especially for monitoring sequelae. In this review, we discuss the use of Nuclear Medicine in the detection, monitoring, and therapeutic evaluation of pulmonary and extrapulmonary sequelae by coronavirus disease 2019., Competing Interests: None., (AJNMMI Copyright © 2020.)

SARS-CoV-2 is responsible for the COVID-19 pandemic. The immune system is a determinant factor in defense against viral infections. Thus, when it acts in a balanced and effective manner the disease is self-limited and benign. Nevertheless, in a significant proportion of the population, the immune response is exaggerated. When infected, patients with diabetes, hypertension, obesity, and cardiovascular disease are more likely to progress to severe forms. These diseases are related to chronic inflammation and endothelial dysfunction. Toll-like receptors are expressed on immune cells and play an important role in the physiopathology of cardiovascular and metabolic diseases. When activated, they can induce release of inflammatory cytokines. Hypercoagulability, hyperinflammation, platelet hyperresponsiveness, and endothelial dysfunction occur in immune system hyperactivity caused by viral activity, thereby increasing the risk of arterial and venous thrombosis. We discuss the interactions between COVID-19, immunity, the endothelium, and coagulation, as well as why cardiometabolic diseases have a negative impact on COVID-19 prognosis., Competing Interests: Conflicts of interest: No conflicts of interest declared concerning the publication of this article.

Objective: Different studies in the last decade have proposed that gene expression alterations that are independent of the DNA sequence may also play an important role in periapical disease. The present study aimed to assess the available evidence supporting a relationship between these alterations and apical periodontitis through a scoping review., Design: Specific strategies were developed for different databases (MEDLINE via PubMed, Cochrane Library, Scopus, Web of Science, and Virtual Health Library) and a search performed by March 1st, 2019. The evidence sources were selected according to the eligibility criteria and underwent a critical appraisal of methodological quality., Results: The initial search retrieved 212 references, with eight eligible articles after the removal of replicates and application of exclusion criteria. Five studies identified altered DNA methylation on inflammatory response genes (FOXP3, CXCL3, FADD, MMP2, MMP9, IFNG, IL4, IL12) on AP patients. Three others identified the alterations on the expression of several microRNAs (miR-29b, 106b, 125b, 143, 146a, 155, 198) during AP. No evidence was identified regarding mechanisms of histone methylation, or of epigenetic heritability or stability., Conclusions: There is available evidence for the involvement of different genetic regulatory mechanisms independent of changes in DNA sequence in the development or severity of apical periodontitis. However, due to methodological limitations, further research must be performed before novel therapies and diagnostic tools for AP may arise from these data., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Background: Individuals affected by heart failure (HF) may present fatigue, dyspnea, respiratory muscle weakness, and sympathetic activity hyperstimulation of the myocardium, among other symptoms. Conducting cardiac rehabilitation (CR) programs can be associated with inspiratory muscle training. The aim of this study was to evaluate the efficacy of inspiratory muscular training (IMT) associated with a CR program on modulating myocardial sympathetic activity and maximal functional capacity, submaximal functional capacity, thickness, and mobility of the diaphragm muscle in patients with HF., Methods: We will conduct a clinical, controlled, randomized, double-blind trial that will include sedentary men and women who are 21-60 years old and who have diagnosed systolic HF and a left ventricular ejection fraction of less than 45%. Participants will be randomly assigned to one of two groups: experimental and control. The control group will follow the conventional CR protocol, and the experimental group will follow the conventional CR protocol associated with IMT 7 days a week. The two proposed exercise protocols will have a frequency of three times a week for a period of 12 weeks. The sympathetic innervation of the cardiac muscle, the maximum and submaximal functional capacity, diaphragm mobility and thickness, and the quality of life of the participants will be evaluated before and after the intervention protocol., Discussion: This clinical trial will be the first study to investigate the additional effects of IMT on CR in sympathetic hyperstimulation in the myocardium. The results of this study will contribute to developing therapeutic strategies collaborating to elucidate whether the association of IMT with CR can induce clinical benefits for patients with HF., Trial Registration: ClinicalTrials.gov identifier: NCT02600000. Registered November 9, 2015. Retrospectively registered.

Background: Left ventricular global longitudinal strain value (GLS) can predict functional capacity in patients with preserved left ventricular ejection fraction (LVEF) heart failure (HF) and to assess prognosis in reduced LVEF HF., Objetive: Correlate GLS with parameters of Cardiopulmonary Exercise Test (CPET) and to assess if they could predict systolic HF patients that are more appropriated to be referred to heart transplantation according to CPET criteria., Methods: Systolic HF patients with LVEF < 45%, NYHA functional class II and III, underwent prospectively CPET and echocardiography with strain analysis. LVEF and GLS were correlated with the following CPET variables: maxVO2, VE/VCO2 slope, heart rate reduction during the first minute of recovery (HRR) and time needed to reduce maxVO2 in 50% after physical exercise (T1/2VO2). ROC curve analysis of GLS to predict VO2 < 14 mL/kg/min and VE/VCO2 slope > 35 (heart transplantation's criteria) was performed., Results: Twenty six patients were selected (age, 47 ± 12 years, 58% men, mean LVEF = 28 ± 8%). LVEF correlated only with maxVO2 and T1/2VO2. GLS correlated to all CPET variables (maxVO2: r = 0.671, p = 0.001; VE/VCO2 slope: r = -0.513, p = 0.007; HRR: r = 0.466, p = 0.016, and T1/2VO2: r = -0.696, p = 0.001). GLS area under the ROC curve to predict heart transplantation's criteria was 0.88 (sensitivity 75%, specificity 83%) for a cut-off value of -5.7%, p = 0.03., Conclusion: GLS was significantly associated with all functional CPET parameters. It could classify HF patients according to the functional capacity and may stratify which patients have a poor prognosis and therefore to deserve more differentiated treatment, such as heart transplantation.

Background: Beneficial effects from non-invasive ventilation (NIV) in acute COPD are well-established, but the impact of nebulization during NIV has not been well described., Aim: To compare pulmonary deposition and distribution across regions of interest with administration of radiolabeled aerosols generated by vibrating mesh nebulizers (VMN) and jet nebulizer (JN) during NIV., Methods: A crossover single dose study involving 9 stable subjects with moderate to severe COPD randomly allocated to receive aerosol administration by the VMN Aerogen and the MistyNeb jet nebulizer operating with oxygen at 8 lpm during NIV. Radiolabeled bronchodilators (fill volume of 3 mL: 0.5 mL salbutamol 2.5 mg + 0.125 mL ipratropium 0.25 mg and physiologic saline up to 3 mL) were delivered until sputtering during NIV (pressures of 12 cmH2O and 5 cmH2O - inspiratory and expiratory, respectively) using an oro-nasal facemask. Radioactivity counts were performed using a gamma camera and regions of interest (ROIs) were delimited. Aerosol mass balance based on counts from the lungs, upper airways, stomach, nebulizer, circuit, inspiratory and expiratory filters, and mask were determined and expressed as a percentage of the total., Results: Both inhaled and lung doses were greater with VMN (22.78 ± 3.38% and 12.05 ± 2.96%, respectively) than JN (12.51 ± 6.31% and 3.14 ± 1.71%; p = 0.008). Residual drug volume was lower in VMN than in JN (3.08 ± 1.3% versus 46.44 ± 5.83%, p = 0.001). Peripheral deposition of radioaerosol was significantly lower with JN than VMN., Conclusions: VMN deposited > 3 fold more radioaerosol into the lungs of moderate to severe COPD patients than JN during NIV., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Introduction: Manual analysis of two-dimensional (2D) scintigraphy to evaluate aerosol deposition is usually subjective and has reduced sensitivity to quantify regional differences between central and distal airways., Aims: (1) To present a method to analyze 2D scans based on three-dimensional (3D)-linked anatomically consistent regions of interest (ROIs); (2) to evaluate peripheral-to-central counts ratio (P/C 2D ) and penetration indices (PIs) for a set of 16 subjects with moderate-to-severe asthma; and (3) to compare the reproducibility of this method against one with manually traced ROIs., Methods: Two-dimensional scans were analyzed using custom software that scaled onto 2D-projections' 3D anatomical features, obtained from population-averaged computed tomography (CT) chest scans. ROIs for a rectangular box (bROI) and an anatomically shaped ROI (aROI) were defined by computer and by manually tracing the standard rectangular box (manual ROI [mROI]). These ROIs were defined five nonconsecutive times for each scan and average value and variability of the P/C 2D were estimated. Based on CT estimates of lung and airways, volumes lying under the bROI and aROI, a 2D penetration index (PI 2D ) and a 3D penetration index (PI 3D ), were defined as volume-normalized ratios of aerosol deposition in central and peripheral ROIs and in central and distal airways, respectively., Results: P/C 2D values and their variability, were influenced by the shape and method to define the ROIs: The P/C 2D was systematically greater and more variable for mROI versus bROI (p < 0.005). The P/C 2D for aROI was higher and its variability lower than those for the bROI (p < 0.001). The PI 2D was in average the same for aROI and bROI, and is substantially (∼30 × ) greater than PI 3D (p < 0.001). Both PI 2D and PI 3D , obtained with our analysis, compared well with literature values obtained with two scans (deposition and volume)., Conclusion: Our results demonstrate that 2D scintigraphy can be analyzed using anatomically based ROIs from 3D CT data, allowing objective and enhanced reproducibility values describing the distribution pattern of radioaerosol deposition in the tracheobronchial tree.

Background: Social security benefits reflect the socioeconomic impact of work incapacity by disease. Cardiovascular diseases (CVD) are the main cause of mortality and mortality worldwide., Objective: To evaluate benefits granted due to CVD in Recife, Pernambuco, Brazil, from 2011 to 2015, from the clinical and economic perspective., Methods: Cross-sectional and descriptive study which collected and analyzed data on benefits granted for disability caused by CVD by the executive management of the National Social Security Institute in Recife, via the Unified System of Information on Benefits., Results: 186,058 benefits were granted from 2011 to 2015, 8,968 (4.8%) corresponded to CVD, of which 6,049 (67.5%) were selected for analysis because they corresponded to the most frequent diseases. About 78% of the beneficiaries were male and 63.8% were within age range 45 to 59 years old. Stroke and heart failure (HF) accounted for the longest sick leaves (133 to 138 days) and highest benefit amounts (about BRL 3,900.00 per month)., Conclusion: While hypertension does not result in as long leaves and costs, it should be prevented for being a significant cause of stroke and HF, both of which account for longer sick leaves and higher social security costs. Improving the quality of life of the population seeks to reduce their impacts on the social security system, the world of work and society at large.

Esophageal squamous cell carcinoma (ESCC) presents poor prognosis, and patients diagnosed with this tumor currently lack target treatments. Therefore, in order to identify potential targets for ESCC treatment, we carried out a transcriptome analysis with ESCC and paired nonmalignant surrounding mucosa samples, followed by a master regulator analysis, and further explored the role of the identified central regulatory genes through in vivo and in vitro assays. Among the transcription factors deregulated/enriched in ESCC, we focused on FOXM1 because of its involvement in the regulation of critical biological processes. A new transcriptome analysis performed with ESCC cell lineage TE-1 showed that the modulation of FOXM1 expression resulted in PIK3R3 expression changes, whereas chromatin immunoprecipitation assay revealed that FOXM1 was capable of binding onto PIK3R3 promoter, thus demonstrating that PIK3R3 is a new FOXM1 target. Furthermore, FOXM1 overexpression resulted in the activation of PIK3/AKT signaling pathway through PIK3R3-mediated AKT phosphorylation. Finally, the analysis of the clinic-pathological data of ESCC patients revealed that overexpression of both FOXM1 and PIK3R3 was associated with poor prognosis, but only the latter was an independent prognosis factor for ESCC patients. In conclusion, our results show that FOXM1 seems to play a central role in ESCC carcinogenesis by upregulating many oncogenes found overexpressed in this tumor. Furthermore, PIK3R3 is a novel FOXM1 target that triggers the activation of the PI3K/AKT pathway in ESCC cells., Competing Interests: CONFLICTS OF INTEREST The authors have no conflicts of interest to disclose.

Purpose: The design development of a small, hand held, battery operated, breath actuated inhaler as a drug/device platform for inhaled insulin posed a number of technical challenges. Our goal was to optimize lung deposition and distribution with aerosol generators producing 3-6 μm particle size distribution., Methods: In silico modeling with computational fluid dynamics (CFD) and in vitro testing of device components were assessed using an Alberta idealized adult airway (Copley, UK) to optimize mouthpiece and aerosol path design for dose delivered distal to the trachea. Human factors use testing was designed to determine the ability to perform inspiratory manuevers with LED guidance within target flow limits. In vivo testing with healthy normal subjects of radiolabeled aerosol compared 2 breathing patterns for lung deposition efficiency, distribution, and subject preference., Results: CFD demonstrated that flows ≤5 L/min and ≥15 L/min reduced the delivery efficiencg. Prototypes tested with inspiratory flow of 10 L/min provided up to 70% of dose delivered distal to the model throat with aerosols of 3 to 6 μm. Users guided by LED were able to inhale for 8-24 s with 5 s breath hold. Lung dose >70% with peripheral to central ratios >2.0 were achieved, with subject preference for the longer inspiratory time with breath hold., Conclusion: The device design phase integration led to a novel design and inspiratory pattern with greater levels of peripheral deposition than previously reported with commercial inhalers. The rationale and process of the application of these methods are described with implications for use in future device development.

Exposure to ionizing radiation greatly increases the risk of developing papillary thyroid carcinoma (PTC), especially during childhood, mainly due to gradual inactivation of DNA repair genes and DNA damages. Recent molecular characterization of PTC revealed DNA methylation deregulation of several promoters of DNA repair genes. Thus, epigenetic silencing might be a plausible mechanism for the activity loss of tumor suppressor genes in radiation-induced thyroid tumors. Herein, we investigated the impact of ionizing radiation on global methylation and CpG islands within promoter regions of homologous recombination (HR) and non-homologous end joining (NHEJ) genes, as well as its effects on gene expression, using two well-established normal differentiated thyroid cell lines (FRTL5 and PCCL3). Our data reveal that X-ray exposure promoted G 2 /M arrest in normal thyroid cell lines. The FRTL5 cells displayed a slower kinetics of double-strand breaks (DSB) repair and a lower long interspersed nuclear element-1 (LINE-1) methylation than the PCCL3 cells. Nevertheless, acute X-ray exposure does not alter the expression of genes involved in HR and NHEJ pathways, apart from the downregulation of Brca1 in thyroid cells. On the other hand, HR and NHEJ gene expressions were upregulated in radiation-induced senescent thyroid cells. Taken together, these data suggest that FRTL5 cells intrinsically have less efficient DNA DSB repair machinery than PCCL3 cells, as well as genomic instability, which could predispose the FRTL5 cells to unrepaired DSB lesions and, therefore, gene mutations.

Objective: The contralateral limbs of patients with unilateral lymphedema in the lower limbs (LLs) can exhibit abnormal lymphatic circulation, even in the absence of lymphedema. This idea is based on a number of reports that have studied isolated cases using lymphoscintigraphy. It is likely that these patients previously had some form of lymphopathy, and the lymphedema arose after the action of some external factor. However, there are no studies in the literature that adequately assess the asymptomatic contralateral limbs of these patients or address the prevalence and characteristics of the abnormal lymphatic circulation in these limbs. The aim of this study was to assess the prevalence of abnormal lymphatic circulation in the asymptomatic contralateral limbs of patients with unilateral lymphedema of the LL., Methods: Forty-three patients from the angiology and vascular surgery ward of the Hospital das Clínicas da Universidade Federal de Pernambuco with unilateral lymphedema of the LL underwent lymphoscintigraphy. All patients received a subcutaneous injection of 0.2 mL (74 MBq) of a solution of dextran 70 labeled with technetium Tc 99m in the first interdigital space of each foot. Images were obtained on two occasions: 10 minutes and 1 hour after the injection. The study design was transversal prospective., Results: Among the 43 asymptomatic LLs, 30 (70%) showed abnormal lymphatic circulation. The lymphoscintigraphic abnormalities found were the following: reduced visualization of the lymphatic vessels and lymph nodes during 1 hour (83%), collateral circulation (30%), visualization of the inguinal and pelvic lymph nodes after at least 1 hour (30%), visualization of the popliteal lymph nodes (20%), dilation and lymphatic tortuosity (20%), and dermal backflow (10%)., Conclusions: In this study,70% of the patients with unilateral lymphedema of the LL had some form of lymphopathy in the contralateral limb during the lymphoscintigraphic examination. These findings could favor the early treatment of these patients to prevent the disease from progressing to its most severe stage., (Copyright © 2017 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.)