Search

BackgroundInadequacies in mental health care coverage remain an enormous problem in the United States. Barriers include scarcity of accessible mental health care professionals. Use of a mental health mobile app incorporating social cognitive theory may help improve confidence in coping skills and improve anxiety and depression. Sinasprite is a mobile app that recruited users via self-referral and clinician referral. Users completed questionnaires to obtain demographic and medical histories. At baseline and 6-week follow-up, users completed the Patient Health Questionnaire 8 (PHQ-8), General Anxiety Disorder 7-Item (GAD-7), and the Coping Self-Efficacy Scale (CSE). It is unknown how self-directed use of a mobile app improves confidence in coping skills and its effects on self-reported depression and anxiety. ObjectiveThe objective of this study was to evaluate the Sinasprite database to assess self-directed engagement and how use of this mobile app impacted self-reported confidence in coping skills and severity of depression and anxiety. MethodsThis retrospective longitudinal study involved users recruited via clinician referral and self-referral through social media and news media. Questionnaires were used to record demographic, medical, and prescription medication histories. Mental health status was assessed via PHQ-8, GAD-7, and CSE questionnaires. A deidentified dataset reporting mobile app use data was provided to investigators. Individuals with verifiable usage data and at least one completed questionnaire at 6 weeks of use were included. Mann–Whitney U and Kruskal-Wallis tests were used to assess whether demographic data and psychotherapy were related to baseline questionnaire scores and usage. A Spearman rho (ρ) test was used to assess the relationship between improvement in the CSE and GAD-7 and PHQ-8 questionnaires. Changes in mental health status were assessed using Wilcoxon signed-rank test. A mixed-effects repeated-measures linear regression model assessed the main effects of time, concomitant counseling, and psychotropic prescription medication use on mental health status. ResultsThirty-four users were eligible for inclusion in the analysis. Users were predominantly female, white, married, and college educated. At baseline, 35% (12/34) of respondents reported the use of individual/group counseling, and 38% (19/34) reported using prescription medications for their mental health. The median user completed 5.7 (interquartile range 2.7-14.1) trackable activities per week. Statistically significant improvements using a Wilcoxon signed-ranked test were observed in the PHQ-8 (P

The natural vanilla market, which generates millions annually, is predominantly dependent on Vanilla planifolia, a species characterized by low genetic variability and susceptibility to pathogens. There is an increasing demand for natural vanilla, prized for its complex, authentic, and superior quality compared to artificial counterparts. Therefore, there is a necessity for innovative production alternatives to ensure a consistent and stable supply of vanilla flavors. In this context, vanilla crop wild relatives (WRs) emerge as promising natural sources of the spice. However, these novel species must undergo toxicity assessments to evaluate potential risks and ensure safety for consumption. This study aimed to assess the non-mutagenic and non-carcinogenic properties of ethanolic extracts from V. bahiana, V. chamissonis, V. cribbiana, and V. planifolia through integrated metabolomic profiling, in vitro toxicity assays, and in silico analyses. The integrated approach of metabolomics, in vitro assays, and in silico analyses has highlighted the need for further safety assessments of Vanilla cribbiana ethanolic extract. While the extracts of V. bahiana, V. chamissonis, and V. planifolia generally demonstrated non-mutagenic properties in the Ames assay, V. cribbiana exhibited mutagenicity at high concentrations (5000 μg/plate) in the TA98 strain without metabolic activation. This finding, coupled with the dose-dependent cytotoxicity observed in WST-1 (Water Soluble Tetrazolium) assays, a colorimetric method that assesses the viability of cells exposed to a test substance, underscores the importance of concentration in the safety evaluation of these extracts. Kaempferol and pyrogallol, identified with higher intensity in V. cribbiana, are potential candidates for in vitro mutagenicity. Although the results are not conclusive, they suggest the safety of these extracts at low concentrations. This study emphasizes the value of an integrated approach in providing a nuanced understanding of the safety profiles of natural products, advocating for cautious use and further research into V. cribbiana mutagenicity., Competing Interests: Declaration of competing interest The authors declare no conflicts of interest., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: The management of vestibular schwannomas (VS) encompasses a choice between conservative "wait-and-scan" (WAS) approach, stereotactic radiosurgery (SRS) or open microsurgical resection. Currently, there is no consensus on the optimal management approach for small to medium sized VS. This study aims to compared outcomes related to hearing in patients with small and medium sized VS who underwent initial treatment with WAS versus SRS., Methods: A systematic review of the available literature was conducted using PubMed/MEDLINE, Embase, and Cochrane up December 08, 2023. Meta-analysis was performed using a random-effect model to calculate mean difference (MD) and relative risk (RR). A leave-one-out analysis was conducted. The risk of bias was assessed via the Risk of Bias in Non-randomized Studies-Interventions (ROBINS-I) and Cochrane Risk of Bias assessment tool (RoB-2). Ultimately, the certainty of evidence was evaluated using the GRADE assessment. The primary outcomes were serviceable hearing, and pure-tone average (PTA). The secondary outcome was the Penn Acoustic Neuroma Quality of Life Scale (PANQOL) total score., Results: Nine studies were eligible for inclusion, comprising a total of 1,275 patients. Among these, 674 (52.86%) underwent WAS, while 601 patients (47.14%) received SRS. Follow-up duration ranged from two to eight years. The meta-analysis indicated that WAS had a better outcome for serviceable hearing (0.47; 95% CI: 0.32 - 0.68; p < 0.001), as well as for postoperative functional measures including PTA score (MD 13.48; 95% CI 3.83 - 23.13; p < 0.01), and PANQOL total score (MD 3.83; 95% CI 0.42 - 7.25; p = 0.03). The overall certainty of evidence ranged from "very low" to "moderate"., Conclusions: Treating small to medium sized VS with WAS increases the likelihood of preserving serviceable hearing and optimized PANQOL overall postoperative score compared to SRS. Nevertheless, the limited availability of literature and the methodological weakness observed in existing studies outline the need for higher-quality studies., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.)

Although Candida albicans is the most frequently identified Candida species in clinical settings, a significant number of infections related to the non- albicans Candida (NAC) species, Candida krusei , has been reported. Both species are able to produce biofilms and have been an important resistance-related factor to antimicrobial resistance. In addition, the microbial relationship is common in the human body, contributing to the formation of polymicrobial biofilms. Considering the great number of reports showing the increase in cases of resistance to the available antifungal drugs, the development of new and effective antifungal agents is critical. The inhibitory effect of Organoselenium Compounds (OCs) on the development of Candida albicans and Candida krusei was recently demonstrated, supporting the potential of these compounds as efficient antifungal drugs. In addition, OCs were able to reduce the viability and the development of biofilms, a very important step in colonization and infection caused by fungi. Thus, the objective of this study was to investigate the effect of the Organoselenium Compounds ( p -MeOPhSe) 2 , (PhSe) 2, and ( p -Cl-PhSe) 2 on the development of dual-species biofilms of Candida albicans and Candida krusei produced using either RPMI-1640 or Sabouraud Dextrose Broth (SDB) media. The development of dual-species biofilms was evaluated by the determination of both metabolic activity, using a metabolic assay based on the reduction of XTT (2,3-bis(2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide sodium salt) assay and identification of either Candida albicans and Candida krusei on CHROMagar Candida medium. Biofilm formation using RPMI-1640 was inhibited in 90, 55, and 20% by 30 µM ( p -MeOPhSe) 2 , (PhSe) 2, and ( p -Cl-PhSe) 2 , respectively. However, biofilms produced using SDB presented an inhibition of 62, 30 and 15% in the presence of 30 µM ( p -MeOPhSe) 2 , (PhSe) 2, and ( p -Cl-PhSe) 2 , respectively. The metabolic activity of 24 h biofilms was inhibited by 35, 30 and 20% by 30 µM ( p -MeOPhSe) 2 , (PhSe) 2, and ( p -Cl-PhSe) 2 , respectively, with RPMI-1640; however, 24 h biofilms formed using SDB were not modified by the OCs. In addition, a great reduction in the number of CFUs of Candida albicans (93%) in biofilms produced using RPMI-1640 in the presence of 30 µM ( p -MeOPhSe) 2 was observed. However, biofilms formed using SDB and treated with 30 µM ( p -MeOPhSe) 2 presented a reduction of 97 and 69% in the number of CFUs of Candida albicans and Candida krusei , respectively. These results demonstrated that Organoselenium Compounds, mainly ( p -MeOPhSe) 2, are able to decrease the metabolic activity of dual-species biofilms by reducing both Candida albicans and Candida krusei cell number during biofilm formation using either RPMI-1640 or SDB. Taken together, these results demonstrated the potential of the OCs to inhibit the development of dual-species biofilms of Candida albicans and Candida krusei .

Introduction . The positioning of γ ray interactions in positron emission tomography (PET) detectors is commonly made through the evaluation of the Anger logic flood histograms. machine learning techniques, leveraging features extracted from signal waveform, have demonstrated successful applications in addressing various challenges in PET instrumentation. Aim . This paper evaluates the use of artificial neural networks (NN) for γ ray interaction positioning in pixelated scintillators coupled to a multiplexed array of silicon photomultipliers (SiPM). Methods . An array of 16 Cerium doped Lutetium-based (LYSO) crystal pixels (cross-section 2 × 2 mm 2 ) coupled to 16 SiPM (S13360-1350) were used for the experimental setup. Data from each of the 16 LYSO pixels was recorded, a total of 160000 events. The detectors were irradiated by 511 keV annihilation γ rays from a Sodium-22 ( 22 Na) source. Another LYSO crystal was used for electronic collimation. Features extracted from the signal waveform were used to train the model. Two models were tested: i) single multiple-class neural network (mcNN), with 16 possible outputs followed by a softmax and ii) 16 binary classification neural networks (bNN), each one specialized in identifying events occurred in each position. Results . Both NN models showed a mean positioning accuracy above 85% on the evaluation dataset, although the mcNN is faster to train. Discussion The method's accuracy is affected by the introduction of misclassified events that interacted in the neighbour's crystals and were misclassified during the dataset acquisition. Electronic collimation reduces this effect, however results could be improved using a more complex acquisition setup, such as a light-sharing configuration. Conclusions The methods comparison showed that mcNN and bNN can surpass the Anger logic, showing the feasibility of using these models in positioning procedures of future multiplexed detector systems in a linear configuration., (Creative Commons Attribution license.)

Autism Spectrum Disorder (ASD) belongs to the group of neurodevelopmental disorders, and has a high prevalence, affecting 1 in 100 children according to data from the World Health Organization (WHO). To be diagnosed with ASD, the child must have persistent deficits in communication and social interactions, and restricted and repetitive patterns of behavior, interests, or activities. Despite its prevalence, the etiology of ASD is still uncertain, with multifactorial characteristics, including those associated with the gestational period, where maternal exposure to biological, chemical, or physical hazards occurs, some of which have already been proposed as causes of ASD outcomes. Since pregnancy requires a balance between the maternal-fetal binomial, the breakdown of this balance caused by such environmental hazards can lead to altered fetal neurodevelopment, including ASD. With this firmly in mind, this review aims to compile the most recent data on the gestational causes that may be associated with the development of ASD to help health professionals identify risk factors and act for the prevention and management of ASD.

Ethnopharmacological Relevance: Genipa americana L. (Rubiaceae) leaves are traditionally used to treat fever, pharyngitis, healing, luxation and bruises., Aim of the Study: This study aimed to investigate the anti-inflammatory effect of the polysaccharide-rich extract of G. americana leaves (PE-Ga) in acute inflammation models and underlying mechanisms associated with platelet activity., Materials and Methods: Rats received PE-Ga (0.3-3.0 mg/kg; IV) 30 min before injection (IP or SC) of zymosan, serotonin, PGE 2 , PLA 2 , PAF or L-arginine, and evaluated in the models of paw edema and acute peritonits. The blockage of plasma serotonin reuptake into platelets was performed with fluoxetine (40 mg/kg; IP)., Results: In vitro, PE-Ga inhibited ADP-induced platelet aggregation up to 49%. In the edema model, PE-Ga reduced (41%) the time-course of the edema induced by zymosan, mainly the last phase (62%), as well as that induced by PLA 2 (32%), PAF (35%), L-arginine (36%), PGE 2 (49%) or serotonin (54% AUC); and reversed paw hypernociception induced by PGE 2 or serotonin. In the peritonitis model, PE-Ga reversed abdominal hypernociception and reduced leukocyte migration induced by zymosan to blood (38%) and peritoneal cavity (55%), mainly neutrophils (70%). PE-GA also decreased leukocyte rolling (32%) and adhesion (47%), and increased the rolling velocity 2.2-fold. In the peritoneal fluid, PE-Ga reversed P-selectin and reduced total proteins (17%), MDA (40%), NO 2 - /NO 3 - (27%), and MPO activity (43%) but increased catalase activity 3.3-fold compared to zymosan. In addition, fluoxetine reversed PE-Ga anti-inflammatory effect on leukocyte migration and adhesion., Conclusions: PE-Ga exerts antiplatelet and anti-inflammatory effects in acute inflammation induced by zymosan, being modulated by P-selectin and platelet serotonin, among other inflammatory mediators., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Objective: This scoping review aimed to systematically identify evidence-based interventions to stimulate healing or protect the harvested palate of patients undergoing gingival grafting., Material and Methods: The study followed guidelines from the Joanna Briggs Institute and PRISMA-ScR (protocol available at osf.io/zhafn). PubMed, Embase, and seven other databases were searched on November 2022, with additional monitoring until April 2023. The inclusion criteria focused on studies evaluating outcomes related to the donor area (palate) and interventions for healing or protecting it, regardless of publication year and language. Data from the included publications was extracted and presented through narrative text, tables, and figures., Results: Eighty-one studies (including 64 clinical trials, four case series, five theses, and eight systematic reviews) and 37 clinical trial records were included. The number of studies on this topic has significantly increased, reflecting a growing interest in the field. Thirty-six interventions with published results and 12 interventions with unpublished results from clinical trial registers were identified. Some promising interventions that showed potential for improving patient-reported outcomes include cyanoacrylate adhesive, platelet-rich fibrin (PRF), and the combination of palatal stents and healing agents., Conclusions: Thirty-six interventions with published results were identified for postoperative use on the harvested palate, showing varying levels of evidence and conflicting effectiveness for specific outcomes., Clinical Relevance: Postoperative discomfort and pain in the palate are commonly experienced by patients undergoing grafting procedures using this region as the donor area. Awareness of the available options and their levels of evidence is crucial for informed decision-making., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Caffeine is a psychoactive substance used worldwide. The present study analyzes the seizure-related behavior and electrocorticographic (ECoG) patterns observed in rats following of a toxic dose of caffeine (150 mg/kg; intraperitoneal). Sixty-three rats were divided into three experiments: 1-Behavior's Description associated with caffeine-induced convulsion; 2- Comparison of the electrocorticographic patterns induced by caffeine and pentylenetetrazole, and 3- Assessment of the electrocorticographic response to antiepileptic drugs (diazepam, phenytoin, and phenobarbital). The behavioral analysis demonstrated tonic-clonic seizures with a loss of postural reflex and a latency of 365.8 s after the caffeine's administration. Caffeine-induced changes in the ECoG were consistent with the development of seizures with rapid evolution and burst potential consistent with the behavioral patterns observed during the caffeine-induced seizure. The ECoG of the brainwaves varied significantly between the seizures caused by caffeine and pentylenetetrazole. The predominant brain forces observed during the seizures were beta-band oscillations. The caffeine-induced seizures were resistant to attempted control with phenytoin and phenobarbital, but responded well to diazepam, which is consistent with a study of Pilocarpine, which showed that diazepam has anticonvulsant effects. These findings are important for the development of effective treatments for caffeine intoxication, in particular for individuals with a low seizure threshold., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Introduction: The knee extension prone test (KEPT) can be a low-cost and affordable alternative for this assess knee hyperextension deficit., Objective: To analyze concurrent validity and reliability of a new method for assessing knee extension prone (knee extension prone test; KEPT)., Methods: Participants were divided into two groups: Group 1 comprised healthy participants (HG) and Group 2 comprised participants with a history of knee injury (IG). Two examiners performed the following evaluations: (1) lateral knee goniometry, (2) anterior tibial inclinometry, (3) lateral photogrammetry in supine, (4) lateral photogrammetry in prone, and (5) KEPT. Concurrent validity was analyzed by Pearson's linear correlation coefficient (r), and intra- and inter-examiner reliability were analyzed by intraclass correlation coefficient (ICC)., Results: KEPT demonstrated good intra-examiner (ICC = 0.85, 95% CI = 0.75-0.89) and excellent inter-examiner (ICC = 0.92, 95% CI = 0.88-0.94) reliability. The standard error of measurement was 0.47° and 1.30° and the minimum detectable change was 2.35° and 6.5° for intra- and inter-examiner agreement, respectively. Concurrent validity of KEPT ranged from moderate to good (r = 0.54-0.78, p < 0.01)., Conclusion: KEPT is a valid and reliable method for assessing knee hyperextension deficit in both healthy individuals and patients with knee injuries., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Lately, the use of zebrafish has gained increased interest in the scientific community as an animal model in preclinical research. However, there is a lack of in vivo imaging tools that ensure animal welfare during acquisition procedures. The use of functional imaging techniques, like Positron Emission Tomography (PET), in zebrafish is limited since it requires the animal to be alive, representing a higher instrumentation complexity when compared to morphological imaging systems. In the present work, a new zebrafish enclosure was developed to acquire in vivo images while monitoring the animal's welfare through its heartbeat. The temperature, dissolved oxygen, and pH range in a closed aquatic environment were tested to ensure that the conditions stay suitable for animal welfare during image acquisitions. The developed system, based on an enclosure with a bed and heartbeat sensors, was tested under controlled conditions in anesthetized fishes. Since the anesthetized zebrafish do not affect the water quality over time, there is no need to incorporate water circulation for the expected time of PET exams (about 30 min). The range of values obtained for the zebrafish heart rate was 88-127 bpm. The developed system has shown promising results regarding the zebrafish's heart rate while keeping the fish still during the long imaging exams. The zebrafish enclosure ensures the animal's well-being during the acquisition of in vivo images in different modalities (PET, Computer Tomography, Magnetic Resonance Imaging), contributing substantially to the preclinical research., 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 Magalhães, Correia, Oliveira, Encarnação, Domingues, Veloso and Silva.)

Background: Malnutrition, lipodystrophy, and dyslipidemia are prevalent characteristics in patients with human immunodeficiency virus (HIV) infection with or without previous treatment. Such a clinical condition can lead to the hypothesis of the presence of hepatic steatosis with possible progression to fibrosis and the risk of hepatocellular carcinoma. Notably, a low phase angle (PA), evaluated by bioelectrical impedance analysis (BIA), is an independent prognostic marker of clinical progression and survival in HIV-infected patients., Aim: To evaluate the relationship between PA and body composition with steatosis and hepatic fibrosis in HIV/hepatitis C virus (HCV)-coinfected patients., Methods: A retrospective observational study by convenience sampling of coinfected HIV/HCV patients, in which all patients underwent transient elastography (Fibroscan) and BIA evaluation. Student's t test was used for group comparisons, and Spearman's or Pearson's correlation test was used when appropriate. The significance level was set at 5%, and analyses were performed using SPSS version 21.0., Results: Forty-three patients who received antiretroviral therapy met the inclusion criteria, and 23 (53.5%) were under treatment with protease inhibitors (PIs). There was no difference in PA between those who used PIs and those who did not ( P = 0.635). There was no correlation between fibrosis grade and PA ( P = 0.355) or lean mass ( P = 0.378). There was a significant inverse correlation between the controlled attenuation parameter (CAP) and lean mass ( P = 0.378), positive correlation between PA and lean mass ( P = 0.378), and negative correlation between PA and fatty mass ( P = 0.378), although the CAP and PA were not correlated. When evaluated by sex, no significant correlations were found., Conclusion: PA determines the muscle function of HIV/HCV-coinfected patients, and the CAP values reinforce the association with lean mass, suggesting that patients require early nutritional interventions., Competing Interests: Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article., (©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.)

Epilepsy is one of the most common neurological disorders, which occurs due to the instability in the inhibitory and excitatory synaptic transmissions in the brain. However, many patients develop resistance to the available drugs, which results in cell degeneration caused due to inadequate control of the seizures. Curcumin, Curcuma longa , is known to be effective for the treatment of organic disorders and may prevent seizures, reduce oxidative stress, and decrease brain damage. Given this, the present study evaluated the antiepileptic effects of C. longa in comparison with both the diazepam and the combined application of these two substances, in terms of their effects on the brain activity and the potential histopathological changes in the hippocampus. This study used male Wistar rats (age: 10-12 weeks; weight: 260 ± 20 g), which were pretreated for 4 days with either saline, C. longa , diazepam, or C. longa + diazepam; and on the fifth day, pentylenetetrazol (PTZ) was administered to induce the seizure. In the C. longa group, a significant increase was observed in the latency of the onset of seizure-related behavior. Surprisingly, however, the combined treatment resulted in the best control of the seizure-related behavior, with the greatest latency of the onset of spasms and isolated clonic seizures. This group also obtained the best results in the electroencephalographic trace and seizure control, with a reduction in the frequency and amplitude of the spike-waves. In the saline group, PTZ significantly reduced the number of cells present in the CA1 and CA3 regions of the hippocampus, while the combined treatment obtained the best results in terms of the preservation of the neuron-like cells. These findings indicate that C. longa may contribute to the control of both seizures and the cell damage induced by PTZ, and that its association with diazepam may be a potentially effective option for the treatment of epilepsy in the future., 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 Nascimento, Ferreira, Silva, Silva, Rodrigues, Teixeira, Azevedo, Araujo, Hamoy, Gonçalves, Coelho, Lopes and Hamoy.)

Monitoring the vital signs of mice is an essential practice during imaging procedures to avoid populational losses and improve image quality. For this purpose, a system based on a set of devices (piezoelectric sensor, optical module and thermistor) able to detect the heart rate, respiratory rate, body temperature and arterial blood oxygen saturation (SpO2) in mice anesthetized with sevoflurane was implemented. Results were validated by comparison with the reported literature on similar anesthetics. A new non-invasive electrocardiogram (ECG) module was developed, and its first results reflect the viability of its integration in the system. The sensors were strategically positioned on mice, and the signals were acquired through a custom-made printed circuit board during imaging procedures with a micro-PET (Positron Emission Tomography). For sevoflurane concentration of 1.5%, the average values obtained were: 388 bpm (beats/minute), 124 rpm (respirations/minute) and 88.9% for the heart rate, respiratory rate and SpO2, respectively. From the ECG information, the value obtained for the heart rate was around 352 bpm for injectable anesthesia. The results compare favorably to the ones established in the literature, proving the reliability of the proposed system. The ECG measurements show its potential for mice heart monitoring during imaging acquisitions and thus for integration into the developed system.

Group B Streptococcus (GBS) infection during pregnancy is involved in maternal sepsis, chorioamnionitis, prematurity, fetal infection, neonatal sepsis, and neurodevelopmental alterations. The GBS-induced chorioamnionitis leads to a plethora of immune and trophoblast cells alterations that could influence endothelial cells to respond differently to angiogenic mediators and alter placental vascular structure and function in pregnant women. In this context, preventive measures are needed to reduce such dysfunctions. As such, we evaluated the effects of a non-lethal exposure to inactivated GBS on trophoblast cells and chorionic villi explants, and if the treatment with uvaol would mitigate these effects. The concentration of 10 6 CFU of GBS was chosen since it was unable to reduce the HTR-8/SVneo cell line nor term chorionic villi explant viability. Raman spectroscopy of trophoblast cells showed significant alterations in their biochemical signature, mostly reverted by uvaol. GBS exposure increased HTR-8/SVneo cells IL-1β and IFN-γ production, phagocytosis, oxidative stress, and decreased trophoblast cell migration. The Ea.hy926 endothelial cell line produced angiopoietin-2, CXCL-8, EGF, FGF-b, IL-6, PlGF, sPECAM-1, and VEGF in culture. When co-cultured in invasion assay with HTR-8/SVneo trophoblast cells, the co-culture had increased production of angiopoietin-2, CXCL-8, FGF-b, and VEGF, while reduced sPECAM-1 and IL-6. GBS exposure led to increased CXCL-8 and IL-6 production, both prevented by uvaol. Chorionic villi explants followed the same patterns of production when exposed to GBS and response to uvaol treatment as well. These findings demonstrate that, even a non-lethal concentration of GBS causes placental inflammation and oxidative stress, reduces trophoblast invasion of endothelial cells, and increases CXCL-8 and IL-6, key factors that participate in vascular dysregulation observed in several diseases. Furthermore, uvaol treatment prevented most of the GBS-provoked changes. Hence, uvaol could prevent the harmful effects of GBS infection for both the mother and the fetus., 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 © 2021 Silva, Silva, Botelho, Tenorio, Marques, Rodrigues, Almeida, Sousa, Pires, Tanabe, Allard, Sébire, Souza, Fonseca, Borbely and Borbely.)

In indicated preterm births such a Gestational Diabetes Mellitus (GDM), little is known about the role of the amnion membranes. Investigating the role of amnion membrane inflammation in response GDM may suggest novel pathophysiologic mechanisms. We hypothesize that increased GDM inflammatory mediators may weaken the amnion membrane predisposing them to infection. Maternal and fetal serum and amnion membrane biopsies were collected from 20 GDM and 38 normoglycemic subjects (control) who underwent elective cesarean sections. Cytokines and adipokines were evaluated in serum and amnion culture supernatant samples. Amnion membrane biopsies from GDM and control subjects were studied: fresh frozen for RNA analysis for Toll-like receptor expression; cultured with LPS to test membrane permeability, and inflammation LPS + anti-TLR4 for testing mechanism. GDM was associated with higher fetal serum leptin (p = 0.004) and IL-10 (p = 0.04) compared to controls. Amnion membrane explants from GDM had higher levels of IL-6 (p = 0.019), and lower expression of Claudin-4 (p = 0.007) and increased permeability (p = 0.046) compared to controls. GDM membranes treated with LPS showed an increased expression of IL-10 (p = 0.013); IL-6 (p = 0.004) and TNF-α (p = 0.0005) but did not affect membrane permeability. LPS and anti-TLR4 antibody treatment reduced the production of TNF-α in controls (p = 0.03) and GDM (p = 0.007) compared to LPS alone. Fetal inflammatory response seems more balanced in GDM and does not impact membrane permeability function even with an infectious stimulus. Light fetal membrane inflammatory response may explain lack of preterm labor in GDM. Concluding, benign inflammation in the membranes may not be harmful for pregnancy maintenance., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Chronic cocaine use has been shown to lead to neurotoxicity in rodents and humans, being associated with high morbidity and mortality rates. However, recreational use, which may lead to addictive behavior, is often neglected. This occurs, in part, due to the belief that exposure to low doses of cocaine comes with no brain damage risk. Cocaine addicts have shown glucose metabolism changes related to dopamine brain activity and reduced volume of striatal gray matter. This work aims to evaluate the morphological brain changes underlying metabolic and locomotor behavioral outcome, in response to a single low dose of cocaine in a pre-clinical study. In this context, a Balb-c mouse model has been chosen, and animals were injected with a single dose of cocaine (0.5 mg/kg). Control animals were injected with saline. A behavioral test, positron emission tomography (PET) imaging, and anatomopathological studies were conducted with this low dose of cocaine, to study functional, metabolic, and morphological brain changes, respectively. Animals exposed to this cocaine dose showed similar open field activity and brain metabolic activity as compared with controls. However, histological analysis showed alterations in the prefrontal cortex and hippocampus of mice exposed to cocaine. For the first time, it has been demonstrated that a single low dose of cocaine, which can cause no locomotor behavioral and brain metabolic changes, can induce structural damage. These brain changes must always be considered regardless of the dosage used. It is essential to alert the population even against the consumption of low doses of cocaine., 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 © 2021 Nicolucci, Pais, Santos, Ribeiro, Encarnação, Silva, Castro, Correia, Veloso, Reis, Lopes, Botelho, Pereira and Priolli.)

Nootkatone (NTK) is a sesquiterpenoid found in essential oils of many species of Citrus (Rutaceae). Considering previous reports demonstrating that NTK inhibited inflammatory signaling pathways, this study aimed to investigate the effects of this compound in mice models of acute and chronic inflammation. Murine models of paw edema induced by carrageenan, dextran, histamine, and arachidonic acid, as well as carrageenan-induced peritonitis and pleurisy, were used to evaluate the effects of NTK on acute inflammation. A murine model of granuloma induced by cotton pellets was used to access the impact of NTK treatment on chronic inflammation. In the acute inflammation models, NTK demonstrated antiedematogenic effects and inhibited leukocyte recruitment, which was associated with decreased vascular permeability, inhibition of myeloperoxidase (MPO), interleukin (IL)1-β, and tumor necrosis factor (TNF)-α production. In silico analysis suggest that NTZ anti-inflammatory effects may also occur due to inhibition of cyclooxygenase (COX)-2 activity and antagonism of the histamine receptor type 1 (H 1 ). These mechanisms might have contributed to the reduction of granuloma weight and protein concentration in the homogenates, observed in the chronic inflammation model. In conclusion, NTK exerted anti-inflammatory effects that are associated with inhibition of IL1-β and TNF-α production, possibly due to inhibition of COX-2 activity and antagonism of the H1 receptor. However, further studies are required to characterize the effects of this compound on chronic inflammation.

Background: Group B streptococcus (GBS) is the main bacteria that infects pregnant women and can cause abortion and chorioamnionitis. The impact of GBS effects on human trophoblast cells remains largely elusive, and actions toward anti-inflammatory strategies in pregnancy are needed. A potent anti-inflammatory molecule, uvaol is a triterpene from olive oil and its functions in trophoblasts are unknown. We aimed to analyze biomechanical and functional effects of inactivated GBS in trophoblast cells, with the addition of uvaol to test potential benefits., Methods: HTR-8/SVneo cells were treated with uvaol and incubated with inactivated GBS. Cell viability and death were analyzed. Cellular elasticity and topography were accessed by atomic force microscopy. Nitrite production was evaluated by Griess reaction. Nuclear translocation of NFkB p65 was detected by immunofluorescence and Th1/Th2 cytokines by bead-based multiplex assay., Results: GBS at 10 8  CFU increased cell death, which was partially prevented by uvaol. Cell stiffness, cytoskeleton organization and morphology were changed by GBS, and uvaol partially restored these alterations. Nuclear translocation of NFkB p65 began 15 min after GBS incubation and uvaol inhibited this process. GBS decreased IL-4 secretion and increased IL-1β, IFN-γ and IL-2, whereas uvaol reverted this., Conclusions: The increased inflammation and cell death caused by GBS correlated with biomechanical and cytoskeleton changes found in trophoblast cells, while uvaol was effective its protective role., General Significance: Uvaol is a natural anti-inflammatory product efficient against GBS-induced inflammation and it has potential to be acquired through diet in order to prevent GBS deleterious effects in pregnancy., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Nowadays, smartphones represent an invaluable tool to access educational material; however, the available information is not always accurate or evidence-based. Therefore, we aimed to evaluate the use of technology by medical students and assess the effect of a newly developed mobile app for the study of human physiology. We used a standardised questionnaire to assess the profile of educational technology use, from which a mobile app (PhysioQuiz) was developed. The effectiveness and user opinion were assessed in a randomised controlled study (n = 110). Of 1022 students enrolled in medical school, 489 (47.9%) participated in the study. Of the respondents, 96.7% used mobile applications, with the main purpose being entertainment (94.7%) and study (81.9%). Only 6.1% reported use of physiology apps. PhysioQuiz use did not yield higher average grades (p = 0.48); however, user opinion demonstrated that it was useful for assisted learning (82.1%) and identification of non-learned content (78.6%) and considered a tool for self-assessment (89.3%). Mobile app use is widespread among medical students but there is a lack of human physiology education apps. A newly developed app for the study of human physiology was useful for assisted learning and considered a tool for self-assessment.

Versican is a proteoglycan known to interact with cells to influence their ability to proliferate, differentiate, migrate, invade and assemble extracellular matrix, with all of these cell functions present during placentation. In the placenta, cytotrophoblast cells have the ability to differentiate into the syncytiotrophoblast, a mechanism that is greatly increased in gestational trophoblastic diseases (GTD). Nevertheless, the molecular signaling underlying the increased syncytiotrophoblast differentiation are still being unveiled and may result in novel therapeutic targets for GTD. Versican expression was investigated to establish its differential expression among GTD (partial moles, complete moles, invasive moles and choriocarcinoma) and the possible functional outcomes from versican gene silencing. Tissue samples had their versican expression evaluated using immunohistochemistry and RT-PCR. BeWo cells were employed for versican silencing with siRNA and the efficiency was confirmed by RT-PCR, immunofluorescence and flow cytometry. Cell death and forskolin-induced syncytialization were analyzed by a morphological analysis and human chorionic gonadotropin (hCG) production using immunofluorescence. Versican V0 and V1 isoforms were mainly expressed in the syncytiotrophoblast and they were the most expressed in benign rather than in malignant tumors. BeWo cells also expressed V0 and V1 isoforms, but only in cells undergoing syncytial fusion. After versican silencing, cell death was greatly increased, whereas spontaneous and forskolin-induced syncytialization decreased as well as hCG production. Versican is differentially expressed in GTD and is important for hydatidiform moles pathophysiology, protecting trophoblast cells from death and playing a role in their differentiation and functionality.

Objective: This study aimed to explore the perceptions and long-term experiences of edentulous patients rehabilitated with single-implant mandibular overdentures (SIMO)., Methods: Thirteen participants, mean age 65.7 years, 69.2% women, who had had their treatment completed for at least 1 year, were invited and included in the study. Focus groups including four to five participants each were conducted, audio and video recorded and transcribed verbatim. Subsequently, the transcripts were analysed according to the principles of thematic analysis., Results: Four major themes emerged as follows: before decision to undergo treatment with SIMO, implant surgery experience, perception of treatment outcomes and impressions about the care received. Lack of information, cost, comorbidities, older age and fear were initial barriers to the decision for treatment. Dissatisfaction with previous treatment and a sense of opportunity motivated the decision. There were ambivalent reports of absence of pain during surgery and discomfort during anaesthesia. Post-surgical recovery exceeded the pre-surgical negative expectations in most cases. There was a tendency for a positive impact of SIMO on the patients' quality of life, comprising improved ability to chew and communicate, dietary diversification, greater comfort and safety, increased self-confidence and social interaction. Few minor inconveniences were reported such as the feeling of insecurity after an episode of denture fracture and the need to use adhesive paste. Satisfaction with the care received and the trust in the dentist and dental team were evident., Conclusion: In general, participants presented positive perceptions and rewarding experiences after rehabilitation with SIMO., (© 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Artemisia vulgaris is one of the important medicinal plant species of the genus Artemisia, which is usually known for its volatile oils. The genus Artemisia has become the subject of great interest due to its chemical and biological diversity as well as the discovery and isolation of promising anti-malarial drug artemisinin. A. vulgaris has a long history in treatment of human ailments by medicinal plants in various parts of the world. This medicinal plant possesses a broad spectrum of therapeutic properties including: anti-malarial, anti-inflammatory, anti-hypertensive, anti-oxidant, anti-tumoral, immunomodulatory, hepatoprotective, anti-spasmodic and anti-septic. These activities are mainly attributed to the presence of various classes of secondary metabolites, including flavonoids, sesquiterpene lactones, coumarins, acetylenes, phenolic acids, organic acids, mono- and sesquiterpenes. Studies related to A. vulgaris morphology, anatomy and phytochemistry has gained a significant interest for better understanding of production and accumulation of therapeutic compounds in this species. Recently, phytochemical and pharmacological investigations have corroborated the therapeutic potential of bioactive compounds of A. vulgaris. These findings provided further evidence for gaining deeper insight into the identification and isolation of novel compounds, which act as alternative sources of anti-malarial drugs in a cost-effective manner. Considering the rising demand and various medical applications of A. vulgaris, this review highlights the recent reports on the chemistry, biological activities and biotechnological interventions for controlled and continuous production of bioactive compounds from this plant species., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Radon is a chemically inert noble radioactive gas found in several radioactive decay chains. In underground mines, especially those that contain or have contained ores associated with uranium-bearing minerals, workers might be exposed to high levels of radon and its decay products (RDP). This work aims to investigate whether the exposure of workers to radon gas and its progeny has been evaluated in Brazilian non-uranium and non-thorium underground mines. Any such results and control measures undertaken or recommended to maintain concentrations under Brazilian occupational exposure limits (OELs) are documented. The methodology we adopted consists of three main phases. The first was an extensive bibliographical survey of the concentration levels of radon and RDP, as well as the radiation dose estimates, considering measurements made heretofore by various Brazilian researchers and exhibiting original measurement work undertaken by the one of the authors (mine O). In the second phase, the values obtained were compared with OELs. In the third phase, any control measures undertaken in mines with high exposure of workers to radon and its progeny were verified, and the adopted controls were determined. Radon concentration data obtained from 52 campaigns in 40 underground mines were analyzed. The results show that assessment of the exposure of workers to radon and its progeny was undertaken in many mines at least once, and that radon levels in 62.5% of the mines, when visited for the first time, were below the Brazilian OELs. As expected, the main control measure adopted or recommended was improvement of the ventilation system.

Mining plays an important role in Brazilian exports. On the other hand, large urban centers like São Paulo, with approximately 21 million inhabitants, also demand an increasing domestic consumption of natural resources, such as construction aggregate. There are many quarries located in the surroundings of urban centers in Brazil, competing with the growth of urbanized areas. Such proximity leads to a series of conflicts involving quarries and surrounding communities, where the increase in noise levels is highlighted. Operations in quarries, in general, are intermittent. Noisier equipment, such as drilling rigs and primary crushers, operates only a few hours during the day, while other operations, such as screening and secondary and tertiary crushing, are more constant. This paper presents a study carried out in a quarry located near São Paulo, where in addition to conventional short term noise measurements at surrounding receptors, one noise monitoring station was installed, allowing to identify the noisiest moments during the quarry operating time. Through data transmitted by wireless technology, it was possible to follow the noise variations emitted from mining activities in real time and observe the noisiest events that were recorded for events that exceeded the established standards. A mobile application associated to this monitoring station facilitated the quarry's manager and employees to access immediately the monitoring information. Therefore, by using this system, it was possible to evaluate the effectiveness of noise reduction measures already taken and indicate what steps still need to be held.