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Thales Paulo Batista,1,2 Vandré Cabral G Carneiro,1,3 Rodrigo Tancredi,4,5 Ana Ligia Bezerra Teles,6 Levon Badiglian-Filho,7 Cristiano Souza Leão8 1Department of Surgery/Oncology, IMIP – Instituto de Medicina Integral Professor Fernando Figueira, 2Department of Surgery, UFPE – Universidade Federal de Pernambuco, 3Department of Gynecology, HCP – Hospital de Câncer de Pernambuco, 4Department of Clinical Oncology, IMIP – Instituto de Medicina Integral Professor Fernando Figueira, 5Department of Clinical Oncology, HCP – Hospital de Câncer de Pernambuco, 6Department of Anaesthesiology, IMIP – Instituto de Medicina Integral Professor Fernando Figueira, Recife, 7Department of Gynecology, AC Camargo Cancer Center, Sao Paulo, 8Department of Surgery, IMIP – Instituto de Medicina Integral Professor Fernando Figueira, Recife, Brazil Purpose: Hyperthermic intraperitoneal chemotherapy (HIPEC) has been considered a promising treatment option for advanced or recurrent ovarian cancer, but there is no clear evidence based on randomized controlled trials to advocate this approach as a standard therapy. In this study, we aim to present the early outcomes and insights after an interim analysis of a pioneering clinical trial in Brazil.Methods: This study was a cross-sectional analysis of early data from our ongoing clinical trial – an open-label, double-center, single-arm trial on the safety and efficacy of using HIPEC for advanced ovarian cancer (ClinicalTrials.gov: NCT02249013). A fast-track recovery strategy was also applied to improve patient outcomes.Results: Nine patients with stage IIIB (n=1) or IIIC (n=8) epithelial malignancies were enrolled until February 2017. The median (range) serum CA125 level at diagnosis was 692 (223.7–6550) U/mL. The median number of preoperative cycles of intravenous (i.v.) chemotherapy was 3 (2–4), resulting in peritoneal cancer index scores of 9 (3–18) at the time of HIPEC. Time of restarting i.v. chemotherapy was 37 (33–50) days with all patients completing 6 cycles as planned. The median operation time was 395 (235–760) minutes, the length of hospital stay was 4 (3–10) days, and all the patients left the ICU on the morning after the procedure. Two patients experienced no postoperative complications, whereas 91% of the complications were minor G1/G2 events. Preliminary assessment also suggested no impairment of the patient’s quality of life.Conclusion: Our comprehensive protocol might represent a promising all-in-one approach for advanced ovarian cancer. The patient recruitment for this trial is ongoing. Keywords: hyperthermia, peritoneal neoplasms, peritoneal surface malignancy, peritoneal carcinomatosis, ovarian neoplasms

Oxidative stress promotes T. cruzi growth and development of chronic Chagas heart dysfunction. However, the literature contains gaps that must be fulfilled, largely due to variations in parasite DTU sources, cell types, mouse strains, and tools to manipulate redox status. We assessed the impact of oxidative environment on parasite burden in cardiomyoblasts and the effects of the Nrf2-inducer COPP on heart function in BALB/c mice infected with either DTU-II Y or DTU-I Colombian T. cruzi strains. Treatment with antioxidants CoPP, apocynin, resveratrol, and tempol reduced parasite burden in cardiomyoblasts H9C2 for both DTUI- and II-strains, while H2O2 increased it. CoPP treatment improved electrical heart function when administered during acute stage of Y-strain infection, coinciding with an overall trend towards increased survival and reduced heart parasite burden. These beneficial effects surpassed those of trypanocidal benznidazole, implying that CoPP directly affects heart physiology. CoPP treatment had beneficial impact on heart systolic function when performed during acute and evaluated during chronic stage. No impact of CoPP on heart parasite burden, electrical, or mechanical function was observed during the chronic stage of Colombian-strain infection, despite previous demonstrations of improvement with other antioxidants. Treatment with CoPP also did not improve heart function of mice chronically infected with Y-strain. Our findings indicate that amastigote growth is responsive to changes in oxidative environment within heart cells regardless of the DTU source, but CoPP influence on heart parasite burden in vivo and heart function is mostly confined to the acute phase. The nature of the antioxidant employed, T. cruzi DTU, and the stage of disease, emerge as crucial factors to consider in heart function studies., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Mata-Santos et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Supplemental dietary rumen available fats show promise as enteric methane (eCH 4 ) mitigators for lactating dairy cows. However, concerns include variability in eCH 4 response and possible negative effects on dairy cow performance. Successful implementation of this mitigation option requires better prediction of responses specifically to rumen available fatty acids (FA) as well as understanding the modulating effects of other dietary and animal characteristics. Using meta-analytic and meta-regression techniques, 35 published studies with diet definition were used to assess changes in eCH 4 emissions and lactation performance associated with supplemental fat, specific supplemental rumen available FA types, and other dietary characteristics. Enteric CH 4 (g/d) was reduced by 3.77% per percentage unit of supplemental rumen available ether extract (EE). Supplemental rumen available PUFA (C18:2 and C18:3) and UFA (C18:1, C18:2, C18:3) mitigated eCH 4 (g/d) emissions in dairy cows by 6.88 and 4.65% per percentage unit increase, respectively. The anti-methanogenic effects of PUFA, MUFA and MCFA increased with correspondingly greater basal dietary levels of each FA type. Higher rumen-degradable starch (RDS; >18% DM) in the basal diet promoted greater reductions in eCH 4 yield (eCH 4 /DMI, g/kg) with supplemental rumen available PUFA and UFA. Both milk fat percentage and yield (kg/d) were reduced with rumen available fat supplementation with a reduction of 7.8% and 6.0%, respectively, relative to control diets. Our results highlight the importance of determining basal levels of the rumen available FA before providing supplemental rumen available FA as an option for enteric eCH 4 mitigation. Dairy nutritionists can use estimates generated from this analysis to predict changes in eCH 4 emissions and dairy cow performance associated with dietary supplementation of rumen available EE and specific rumen available FA types for the purpose of eCH 4 mitigation., (The Authors. Published by Elsevier Inc. on behalf of the American Dairy Science Association®. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).)

Monitoring central venous pressure (CVP) is crucial for managing critically ill patients yet poses challenges in pediatric cases. This study aimed to correlate CVP with hepatic vein Doppler and IVC ultrasound variables in children. Mechanically ventilated children underwent simultaneous ultrasound and CVP measurements. Hepatic vein Doppler assessed peak velocities (A, S, V, D) and systolic filling fraction. IVC ultrasound included respiratory variability indices, IVC/aorta ratio, and IVC/body surface area ratio. Fifty-three children were included (median age of 8.3 months and weight of 6.3 kg). Significant correlations were found between CVP values and all hepatic vein Doppler-based variables. The strongest correlation was found between CVP and the sum of the absolute values of the A- and D-wave peak velocities (AD velocity), with a ρ = 0.61 (95% confidence interval [CI] of 0.40 to 0.75; p < 0.001). The AD velocity > 38.55 cm/s was able to discriminate patients with CPV > 12 mmHg with a sensitivity of 100%, specificity of 95.3%, positive predictive value of 83.3%, and negative predictive value of 100%. No correlations were observed between CVP and variables derived from IVC respiratory variability indices or the IVC/aorta ratio. Conclusion: Hepatic vein Doppler ultrasound provides variables that significantly correlate with CVP and may be useful for estimating cardiac preload in mechanically ventilated children. Indices derived from IVC ultrasound were not reliable for estimating CVP. What is known? • Increased central venous pressure (CVP) can cause interstitial edema and reduce vital organ perfusion, leading to organic dysfunctions, with encapsulated organs such as the kidneys and liver being at higher risk. • However, measuring CVP in children poses challenges due to the difficulties and risks of central venous catheterization, frequent partial or total luminal obstructions in venous catheters, and potential technical errors in measurements. What is new? • Variables obtained through hepatic vein Doppler ultrasonography outperformed those obtained by inferior vena cava ultrasound for estimating CVP in this population. • Hepatic vein Doppler ultrasonography holds potential as an accurate, safe, and non-invasive method for discriminating patients with increased cardiac preload., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Fluids are often administered for various purposes, such as resuscitation, replacement, maintenance, nutrition, or drug infusion. However, its use is not without risks. Critically ill patients are highly susceptible to fluid accumulation (FA), which is associated with poor outcomes, including organ dysfunction, prolonged mechanical ventilation, extended hospital stays, and increased mortality. This study aimed to assess the association between FA and poor outcomes in critically ill children., Methods: In this systematic review and meta-analysis, we searched PubMed, Embase, ClinicalTrials.gov, and Cochrane Library databases from inception to May 2024. Relevant publications were searched using the following terms: child, children, infant, infants, pediatric, pediatrics, critically ill children, critical illness, critical care, intensive care, pediatric intensive care, pediatric intensive care unit, fluid balance, fluid overload, fluid accumulation, fluid therapy, edema, respiratory failure, respiratory insufficiency, pulmonary edema, mechanical ventilation, hemodynamic instability, shock, sepsis, acute renal failure, acute kidney failure, acute kidney injury, renal replacement therapy, dialysis, mortality. Paediatric studies were considered eligible if they assessed the effect of FA on the outcomes of interest. The main outcome was all-cause mortality. Pooled analyses were performed by using random-effects models. This review was registered on PROSPERO (CRD42023432879)., Findings: A total of 120 studies (44,682 children) were included. Thirty-five FA definitions were identified. In general, FA was significantly associated with increased mortality (odds ratio [OR] 4.36; 95% confidence interval [CI] 3.53-5.38), acute kidney injury (OR 1.98; 95% CI 1.60-2.44), prolonged mechanical ventilation (weighted mean difference [WMD] 38.1 h, 95% CI 19.35-56.84), and longer stay in the intensive care unit (WMD 2.29 days; 95% CI 1.19-3.38). The percentage of FA was lower in survivors when compared to non-survivors (WMD -4.95 [95% CI, -6.03 to -3.87]). When considering only studies that controlled for potential confounding variables, the pooled analysis revealed 6% increased odds of mortality associated with each 1% increase in the percentage of FA (adjusted OR = 1.06 [95% CI, 1.04-1.09)., Interpretation: FA is significantly associated with poorer outcomes in critically ill children. Thus, clinicians should closely monitor fluid balance, especially when new-onset or worsening organ dysfunction occurs in oedematous patients, indicating potential FA syndrome. Future research should explore interventions like restrictive fluid therapy or de-resuscitation methods. Meanwhile, preventive measures should be prioritized to mitigate FA until further evidence is available., Funding: None., Competing Interests: The authors have no conflicts of interest to disclose., (© 2024 The Author(s).)

Obesity is a highly prevalent disease with numerous complications. Both intensive medical treatment with the use of pharmacological drugs and bariatric surgery are current options. The objective of this meta-analysis was to compare, in the long-term, intensive medical treatment and surgery based on twelve parameters related to weight loss, cardiovascular and endocrine changes. A review of the literature was conducted in accordance with the PRISMA guidelines (PROSPERO: CRD42021265637). The literature screening was done from inception to October 2023 through PubMed, EMBASE and Web of Science databases. We included randomized clinical trials that had separate groups for medical treatment and bariatric surgery as an intervention for obesity. The risk of bias was assessed through RoB2. A meta-analysis was performed with measures of heterogeneity and publication bias. Subgroup analysis for each surgery type was performed. Data is presented as forest-plots. Reviewers independently identified 6719 articles and 6 papers with a total 427 patients were included. All studies were randomized controlled trials, three had a follow up of 5 years and two had a follow up of 10 years. Both groups demonstrated statistical significance for most parameters studied. Surgery was superior for weight loss (- 22.05 kg [- 28.86; - 15.23), total cholesterol (- 0.88 [- 1.59; - 0.17]), triglycerides (- 0.70 [- 0.82; - 0.59]), HDL (0.12 [0.02; 0.23]), systolic pressure (- 4.49 [- 7.65; - 1.33]), diastolic pressure (- 2.28 [- 4.25; - 0.31]), Hb glycated (- 0.97 [- 1.31; - 0.62]), HOMA IR (- 2.94; [- 3.52; - 2.35]) and cardiovascular risk (- 0.08; [- 0.10; - 0.05]). Patient in the surgical treatment group had better long term outcomes when compared to the non-surgical group for most clinical parameters., (© 2024. The Author(s).)

Introduction: The aim of the present study was to use cluster analysis and ensemble methods to evaluate the association between quality of life, socio-demographic factors to predict nutritional risk in community-dwelling Brazilians aged 80 and over., Methods: This cross-sectional study included 104 individuals, both sexes, from different community locations. Firstly, the participants answered the sociodemographic questionnaire, and were sampled for anthropometric data. Subsequently, the Mini-Mental State Examination (MMSE) was applied, and Mini Nutritional Assessment Questionnaire (MAN) was used to evaluate their nutritional status. Finally, quality of life (QoL) was assessed by a brief version of World Health Organizations' Quality of Life (WHOQOL-BREF) questionnaire and its older adults' version (WHOQOL-OLD)., Results: The K-means algorithm was used to identify clusters of individuals regarding quality-of-life characteristics. In addition, Random Forest (RF) and eXtreme Gradient Boosting (XGBoost) algorithms were used to predict nutritional risk. Four major clusters were derived. Although there was a higher proportion of individuals aged 80 and over with nutritional risk in cluster 2 and a lower proportion in cluster 3, there was no statistically significant association. Cluster 1 showed the highest scores for psychological, social, and environmental domains, while cluster 4 exhibited the worst scores for the social and environmental domains of WHOQOL-BREF and for autonomy, past, present, and future activities, and intimacy of WHOQOL-OLD., Conclusion: Handgrip, household income, and MMSE were the most important predictors of nutritional. On the other hand, sex, self-reported health, and number of teeth showed the lowest levels of influence in the construction of models to evaluate nutritional risk. Taken together, there was no association between clusters based on quality-of-life domains and nutritional risk, however, predictive models can be used as a complementary tool to evaluate nutritional risk in individuals aged 80 and over., 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 © 2024 Brech, da Silva, Alonso, Machado-Lima, da Silva, Micillo, Bastos and de Aquino.)

Anti-NMDA receptor encephalitis (NMDARE), an autoimmune encephalitis associated with autoantibodies against the N-methyl-D-aspartate (NMDA) receptor, affects predominantly young women and is associated with psychiatric symptoms, seizures, movement disorders, and autonomic instability. Traditional treatments of anti-NMDA receptor encephalitis involve corticosteroids, intravenous immunoglobulin, plasmapheresis, cyclophosphamide, and rituximab. However, many controversies remain in the treatment for NMDA receptor encephalitis, such as optimal timing and combination of different immunotherapies, the role of newer strategies (e.g., bortezomib or tocilizumab) for severe and refractory patients, and the need or not for long-term immunosuppression. Our goal was to perform a scoping review to discuss the controversial topics of immunotherapy for NMDA receptor encephalitis and propose operational definitions to guide clinical practice and future research in the field., (© 2023. Fondazione Società Italiana di Neurologia.)

Aims: The purpose of this systematic review was to evaluate the cost-effectiveness and acceptance of children and their parents of the Hall technique (HT) for dental rehabilitation in pediatric dentistry., Background: The approach of the HT is that of minimally invasive treatment of the dental element and is used exclusively on primary molars. Various studies in the literature point to HT as a restorative option well accepted by children and parents and quite predictable, with low retreatment rates and good cost-effectiveness for the management of primary molars with carious lesions. However, no systematic review in the literature has approached randomized clinical trials on these topics to produce a high level of evidence and help establish clinical HT protocols., Review Results: Eight articles were selected for the systematic review. The HT was more cost-effective than procedures using other restorative materials. Regarding acceptance, in terms of esthetics, high percentages of satisfaction were reported for parents and children, with a divergence between studies in the comparison of esthetic preference with atraumatic restorative treatment. However, when considering crown cementation pain, comfort, anxiety, preference, and satisfaction, the HT was generally better evaluated when compared to other restorative materials., Conclusion: The HT is an excellent restorative option when considering cost-effectiveness and acceptance and is recommended for use in daily clinical practice., Clinical Significance: Results indicate that HT is superior to other restorative materials regarding its acceptance by children and parents in terms of pain, comfort, anxiety, and crown preference and satisfaction. There were also high percentages of satisfaction with esthetics. Hall technique may initially appear expensive for dentists, but its effectiveness over time and the lesser need for consultations and reinventions ensure better cost-benefit than other restorative materials. How to cite this article: Valentim FB, Moreira KMS, Carneiro VC, et al . Cost-effectiveness and Acceptance in Children and Parents of the Hall Technique: Systematic Review of Clinical Trials. J Contemp Dent Pract 2023;24(12):1016-1025.

Herpesvirus is associated with various neurological disorders and a specific diagnosis is associated with a better prognosis. MicroRNAs (miRNAs) are potential diagnostic and prognostic biomarkers of neurological diseases triggered by herpetic infection. In this review, we discuss miRNAs that have been associated with neurological disorders related to the action of herpesviruses. Human miRNAs and herpesvirus-encoded miRNAs were listed and discussed. This review article will be valuable in stimulating the search for new diagnostic and prognosis alternatives and understanding the role of these miRNAs in neurological diseases triggered by herpesviruses.

METTL3 is the major writer of N6-Methyladenosine (m 6 A) and has been associated with controversial roles in cancer. This is best illustrated in urothelial carcinoma of the bladder (UCB), where METTL3 was described to have both oncogenic and tumor-suppressive functions. Here, we reinvestigated the role of METTL3 in UCB. METTL3 knockout reduced the oncogenic phenotype and m 6 A levels of UCB cell lines. However, complete depletion of METTL3/m 6 A was not achieved due to selection of cells expressing alternative METTL3 isoforms. Systematic vulnerability and inhibitor response analyses suggested that uroepithelial cells depend on METTL3 for viability. Furthermore, expression and survival analyses of clinical data revealed a complex role for METTL3 in UCB, with decreased m 6 A mRNA levels in UCB tumors. Our results suggest that METTL3 expression may be a suitable diagnostic UCB biomarker, as the enzyme promotes UCB formation. However, the suitability of the enzyme as a therapeutic target should be evaluated carefully., Competing Interests: M.H. is a consultant for Moderna Inc., (© 2023 The Author(s).)

Wastewater-based epidemiology can be a complementary approach for monitoring SARS-CoV-2 prevalence, diversity, and geographic distribution. It is a complementary approach regarding its prevalence and diversity, and geographic distribution. The study aimed to evaluate the genetic diversity of SARS-CoV-2 in two wastewater treatment plants (WWTPs) in Rio de Janeiro, Brazil. Samples were collected over a period of January to December 2021 and were concentrated with PEG8000 and the presence of SARS-CoV-2 was detected using E and N1 genes. Partial sequencing of the SARS-CoV-2 genomes resulted in the identification of variants of concern and variants of interest throughout the collection period. It was possible to identify the Mu, Delta, Gamma and Omicron variants in WWTP1; on the contrary, no variants were observed in WWTP2. To the best of our knowledge, we detected the variant Mu (B.1.621) containing characteristic mutations (S:E484K, S:N501Y) from WWTP, for the first time, in Brazil. Another Mu variant detected from clinical surveillance was announced one month after our finding. The detection of SARS-CoV-2 in wastewater can serve as a tool to monitor the prevalence and epidemiology in each community, helping to understand the spread of the virus among the population.

Despite extensive research on overweight and obesity, there are few studies that present longitudinal statistical analyses among non-institutionalized older adults, particularly in low- and middle-income countries. This study aimed to assess the prevalence and factors associated with excess weight in older adults from the same cohort over a period of fifteen years. A total of 264 subjects aged (≥60 years) from the SABE survey (Health, Wellbeing and Aging) in the years 2000, 2006, 2010, and 2015 in the city of São Paulo, Brazil, were evaluated. Overweight was assessed by a BMI of ≥28 kg/m 2 . Multinomial logistic regression models adjusted for sociodemographic and health data were used to assess factors associated with excess weight. After normal weight, overweight was the most prevalent nutritional status in all evaluated periods: 34.02% in 2000 (95%CI: 28.29-40.26); 34.86% in 2006 (95%CI: 28.77-41.49%); 41.38% in 2010 (95%CI: 35.25-47.79); 33.75% in 2015 (95%CI: 28.02-40.01). Being male was negatively associated with being overweight in all years (OR: 0.34 in 2000; OR: 0.36 in 2006; OR: 0.27 in 2010; and OR: 0.43 in 2015). A greater number of chronic diseases and worse functionality were the main factors associated with overweight, regardless of gender, age, marital status, education, physical activity, and alcohol or tobacco consumption. Older adults with overweight and obesity, a greater number of chronic diseases, and difficulties in carrying out daily tasks required a greater commitment to healthcare. Health services must be prepared to accommodate this rapidly growing population in low- and middle-income countries.

The ability to drive depends on the motor, visual, and cognitive functions, which are necessary to integrate information and respond appropriately to different situations that occur in traffic. The study aimed to evaluate older drivers in a driving simulator and identify motor, cognitive and visual variables that interfere with safe driving through a cluster analysis, and identify the main predictors of traffic crashes. We analyzed the data of older drivers (n = 100, mean age of 72.5 ± 5.7 years) recruited in a hospital in São Paulo, Brazil. The assessments were divided into three domains: motor, visual, and cognitive. The K-Means algorithm was used to identify clusters of individuals with similar characteristics that may be associated with the risk of a traffic crash. The Random Forest algorithm was used to predict road crash in older drivers and identify the predictors (main risk factors) related to the outcome (number of crashes). The analysis identified two clusters, one with 59 participants and another with 41 drivers. There were no differences in the mean of crashes (1.7 vs. 1.8) and infractions (2.6 vs. 2.0) by cluster. However, the drivers allocated in Cluster 1, when compared to Cluster 2, had higher age, driving time, and braking time ( p < 0.05). The random forest performed well (r = 0.98, R 2 = 0.81) in predicting road crash. Advanced age and the functional reach test were the factors representing the highest risk of road crash. There were no differences in the number of crashes and infractions per cluster. However, the Random Forest model performed well in predicting the number of crashes.

Trauma-related injuries in traffic-accident victims can be quite serious. Evaluating the factors contributing to traffic accidents is critical for the effective design of programs aimed at reducing traffic accidents. Therefore, this study identified which factors related to traffic accidents are associated with injury severity in hospitalized victims. Factors related to traffic accidents, injury severity, disability and data collected from blood toxicology were evaluated, along with associated severity and disability indices with data collected from toxicology on victims of traffic accidents at the largest tertiary hospital in Latin America. One hundred and twenty-eight victims of traffic accidents were included, of whom the majority were young adult men, motorcyclists, and pedestrians. The most frequent injuries were traumatic brain injury and lower-limb fractures. Alcohol use, hit-and-run victims, and longer hospital stays were shown to lead to greater injury severity. Women, elderly individuals, and pedestrians tend to suffer greater disability post-injury. Therefore, traffic accidents occur more frequently among young male adults, motorcyclists, and those who are hit by a vehicle, with trauma to the head and lower limbs being the most common injury. Injury severity is greater in pedestrians, elderly individuals and inebriated individuals. Disability was higher in older individuals, in women, and in pedestrians.

Background: Parkinson's disease (PD) and sarcopenia share similar pathophysiological mechanisms., Objective: Estimate the prevalence of sarcopenia in PD patients and describe clinical and demographic features associated with sarcopenia., Methods: A cross-sectional study was carried out at a tertiary public hospital in Brazil. A modified HY scale of stage 1 to 3, being at least 40 years old and having the ability to stand and walk unassisted were required for eligibility. We evaluated physical performance and muscle mass using DEXA., Results: The study population comprised 124 patients, of which 53 (42.7%) were women. The mean age and mean disease duration were 65.8±10.5 and 10.1±5.8 years, respectively. The mean handgrip strength of 20.4±6.9 in woman and 34.6±8.4 kg in men. Moreover, 50.8% patients had positive SARC-F, 20% patients had probable sarcopenia, 9.6% confirmed sarcopenia, and 16.8% patients showed low muscle mass quantity measured by DEXA. Lower Levodopa Equivalent Dosage (LED) and calf circumference (CC) were independently associated with confirmed sarcopenia. LLED, higher MDS-UPDRS Part III, and lower MMSE scores were independently associated with probable sarcopenia. The CC demonstrated accuracy to identify PD patients with confirmed sarcopenia with a cut-off of <31 cm in women and <34 cm in men., Conclusion: We found low prevalence of confirmed sarcopenia among PD patients. We propose that healthcare providers introduce measuring CC, which is a quick and inexpensive method to assess for sarcopenia in PD patients.

This study aimed to predict dietary recommendations and compare the performance of algorithms based on collaborative filtering for making predictions of personalized dietary recommendations. We analyzed the baseline cross-sectional data (2008-2010) of 12,667 participants of the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil). The participants were public employees of teaching and research institutions, aged 35-74 years, and 59% female. A semiquantitative Food Frequency Questionnaire (FFQ) was used for dietary assessment. The predictions of dietary recommendations were based on two machine learning (ML) algorithms-user-based collaborative filtering (UBCF) and item-based collaborative filtering (IBCF). The ML algorithms had similar precision (88-91%). The error metrics were lower for UBCF than for IBCF: with a root mean square error (RMSE) of 1.49 vs. 1.67 and a mean square error (MSE) of 2.21 vs. 2.78. Although all food groups were used as input in the system, the items eligible as recommendations included whole cereals, tubers and roots, beans and other legumes, oilseeds, fruits, vegetables, white meats and fish, and low-fat dairy products and milk. The algorithms' performances were similar in making predictions for dietary recommendations. The models presented can provide support for health professionals in interventions that promote healthier habits and improve adherence to this personalized dietary advice.

The prevalence of hernias in patient with cirrhosis can reach up to 40%. The pathophysiology of cirrhosis is closely linked to that of the umbilical hernia, but other types are also common in this population. The aim of this study is to evaluate factors that influence in the prognosis after hernia repair in patients with cirrhosis. A historical cohort of 6419 patients submitted to hernia repair was gathered. Clinical, epidemiological data and hernia characteristics were obtained. For patient with cirrhosis, data from exams, surgery and follow-up outcomes were also analyzed. Survival curves were constructed to assess the impact of clinical and surgical variables on survival. 342 of the 6352 herniated patients were cirrhotic. Patient with cirrhosis had a higher prevalence of umbilical hernia (67.5% × 24.2%, P < .001) and a lower prevalence of epigastric (1.8% × 9.0%, P < .001) and lumbar (0% × 0.18%, P = .022). There were no significant differences in relation to inguinal hernia (P = .609). Ascites was present in 70.1% of patient with cirrhosis and its prevalence was different in relation to the type of hernia (P < .001). The survival curve showed higher mortality for emergency surgery, MELD > 14 and ascites (HR 12.6 [3.79-41.65], 4.5 [2.00-10.34], and 6.1 [1.15-20.70], respectively, P < .05). Hernia correction surgery in patient with cirrhosis has a high mortality, especially when performed under urgent conditions associated with more severe clinical conditions of patients, such as the presence of ascites and elevated MELD., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2022 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Machine learning investigates how computers can automatically learn. The present study aimed to predict dietary patterns and compare algorithm performance in making predictions of dietary patterns., Methods: We analysed the data of public employees (n = 12,667) participating in the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil). The K-means clustering algorithm and six other classifiers (support vector machines, naïve Bayes, K-nearest neighbours, decision tree, random forest and xgboost) were used to predict the dietary patterns., Results: K-means clustering identified two dietary patterns. Cluster 1, labelled the Western pattern, was characterised by a higher energy intake and consumption of refined cereals, beans and other legumes, tubers, pasta, processed and red meats, high-fat milk and dairy products, and sugary beverages; Cluster 2, labelled the Prudent pattern, was characterised by higher intakes of fruit, vegetables, whole cereals, white meats, and milk and reduced-fat milk derivatives. The most important predictors were age, sex, per capita income, education level and physical activity. The accuracy of the models varied from moderate to good (69%-72%)., Conclusions: The performance of the algorithms in dietary pattern prediction was similar, and the models presented may provide support in screener tasks and guide health professionals in the analysis of dietary data., (© 2022 The British Dietetic Association Ltd.)

Background: Telemedicine allows Parkinson disease (PD) patients to overcome physical barriers to access health care services and increases accessibility for people with mobility impairments., Objective: To investigate the feasibility indicators of a telehealth intervention for PD patients, including patient recruitment, attendance, technical issues, satisfaction, and benefits on levels of physical activity and sleep., Methods: We conducted a single-center, single-arm study of telehealth video consultations using WhatsApp (Meta Platforms, Inc., Menlo Park, CA, USA). Also, we collected the feasibility indicators as the primary endpoints. All the patients in the study were previously evaluated in person by the same team., Results: Patient recruitment, attendance, and technical issues rates were 61.3%, 90.5%, and 13.3%, respectively, with good scores of patient acceptance and satisfaction with the study intervention. The telehealth intervention improved physical activity, including the number of walks for at least 10 continuous minutes ( p  = 0.009) and the number of moderate-intensity activities lasting at least 10 continuous minutes ( p  = 0.001). The Pittsburgh sleep quality index (PSQI) scores also improved for one of its components: perceived sleep duration ( p  < 0.001) and for total Pittsburgh score ( p  < 0,001). The average travel time saving was 289.6 minutes, and money-saving was R$106.67 (around USD 18; almost 10% of the current minimum wage in Brazil)., Conclusions: Direct-to-patient telehealth video consultations proved to be feasible and effective and had a positive impact on physical activity levels and sleep in PD patients., Competing Interests: The authors have no conflict of interests to declare., (Academia Brasileira de Neurologia. This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/).)

Epigenetic mechanisms are responsible for a wide range of biological phenomena in insects, controlling embryonic development, growth, aging and nutrition. Despite this, the role of epigenetics in shaping insect-pathogen interactions has received little attention. Gene expression in eukaryotes is regulated by histone acetylation/deacetylation, an epigenetic process mediated by histone acetyltransferases (HATs) and histone deacetylases (HDACs). In this study, we explored the role of the Aedes aegypti histone acetyltransferase CBP (AaCBP) after infection with Zika virus (ZIKV), focusing on the two main immune tissues, the midgut and fat body. We showed that the expression and activity of AaCBP could be positively modulated by blood meal and ZIKV infection. Nevertheless, Zika-infected mosquitoes that were silenced for AaCBP revealed a significant reduction in the acetylation of H3K27 (CBP target marker), followed by downmodulation of the expression of immune genes, higher titers of ZIKV and lower survival rates. Importantly, in Zika-infected mosquitoes that were treated with sodium butyrate, a histone deacetylase inhibitor, their capacity to fight virus infection was rescued. Our data point to a direct correlation among histone hyperacetylation by AaCBP, upregulation of antimicrobial peptide genes and increased survival of Zika-infected-A. aegypti., Competing Interests: The authors have declared that no competing interests exist.

Stressing agents can cause morphophysiological and behavioural changes in several animals, including birds, which are good study models for environmental biomonitoring. The heterophil/lymphocyte ratio (H/L) is an efficient indicator of chronic stresses in birds. In this study, we aimed to compare the H/L ratio of birds between the areas with different levels of urbanisation, anthropogenic noise and carbon monoxide (CO) emission rates. A total of 1288 birds were captured in six Cerrado forest fragments between 2013 and 2019, from which we took blood samples to produce blood smears. In each of these fragments, the noise level was measured with a sound pressure level metre. The CO rates were obtained from the National Institute for Space Research database (INPE-Brazil). There was a higher H/L ratio in individuals captured in urban areas or close to urbanisation with high anthropogenic noise levels and high CO rates, and a lower H/L ratio in individuals from preserved areas, far from urban environments with low noise levels and low CO rates. Six species (Antilophia galeata, Leoptopogon amaurocephalus, Cnemotriccus fuscatus, Lathrotriccus euleri, Turdus leucomelas and Eucometis penicillata) showed a significant difference between the areas and followed the pattern shown by the individuals. The present study showed that birds living in the urban and peri-urban sites have higher values of H/L ratio than birds from rural sites. These results suggest that the H/L ratio can be used as an environmental biomonitoring tool and an efficient parameter to assess chronic stress in birds in degraded environments., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Social distancing in response to the COVID-19 pandemic brought several modifications in our daily lives. With these changes, some people have reported alterations in their feelings of how fast time was passing. In this study, we assessed whether and how social distancing and the evolution of the COVID-19 pandemic influenced participants' time awareness and production of time intervals. Participants ( n = 3855) filled in the first questionnaire approximately 60 days after the start of social distancing in Brazil and weekly questionnaires for 15 weeks during social distancing. Our results indicate that time was perceived as expanded at the beginning, but this feeling decreased across the weeks. Time awareness was strongly associated with psychological factors such as loneliness, stress, and positive emotions, but not with time production. This relation was shown between participants and within their longitudinal reports. Together, our findings show how emotions are a crucial aspect of how time is felt.

DNA methylation is an important epigenetic modification that has been repeatedly implied in organismal adaptation. However, many previous studies that have linked DNA methylation patterns to environmental parameters have been limited by confounding factors, such as cell-type heterogeneity and genetic variation. In this study, we analyzed DNA methylation variation in marbled crayfish, a clonal and invasive freshwater crayfish that is characterized by a largely tissue-invariant methylome and negligible genetic variation. Using a capture-based subgenome bisulfite sequencing approach that covers a small, variably methylated portion of the marbled crayfish genome, we identified specific and highly localized DNA methylation signatures for specimens from geographically and ecologically distinct wild populations. These results were replicated both biologically and technically by re-sampling at different time points and by using independent methodology. Finally, we show specific methylation signatures for laboratory animals and for laboratory animals that were reared at a lower temperature. Our results thus demonstrate the existence of context-dependent DNA methylation signatures in a clonal animal., 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 Tönges, Venkatesh, Andriantsoa, Hanna, Gatzmann, Raddatz, Carneiro and Lyko.)

Statement of Problem: Misfits at the implant-abutment joint (IAJ) can cause the biological and mechanical failure of implant therapy. Standard parallel periapical radiography (PERI) is the method of choice for assessing the fitting of implant-supported prostheses. Although current guidelines do not support the use of cone beam computed tomography (CBCT) solely for misfit detection, CBCT scans can also register misfits as imaging findings. Whether the material used for prostheses manufacturing influences misfit appearance in PERI and CBCT images is unknown., Purpose: The purpose of this in vitro study was to assess the influence of the type of prosthesis material on misfit detection at the IAJ by using PERI and CBCT., Material and Methods: Thirty-two implants with an external hexagon connection were placed in dried human mandibles. Implant-supported crowns were manufactured with different materials and allocated to 3 experimental groups: metal-ceramic (MC), titanium abutment veneered with acrylic resin (TIT), and zirconia abutment veneered with glass-ceramic (ZIR). All crowns were installed both with and without a simulated 200-μm-thick gap at the IAJ (n=64) and were assessed by PERI and CBCT scans. Four dentists evaluated the images for the presence or absence of misfit. Statistical analysis included the Kappa test and areas under the receiver operating characteristics curve (Az values) comparisons (α=.05)., Results: Kappa values indicated almost perfect intraevaluator and interevaluator reproducibility for PERI and ranged from fair to almost perfect for CBCT. For PERI, Az values were not significantly different among the MC (0.995), TIT (0.997), and ZIR groups (1.000) (P>.05). Regarding CBCT, the Az values found for TIT (0.941) and MC (0.890) were significantly higher than for ZIR (0.762) (P<.05). Az values for PERI were significantly higher than for CBCT (P<.05)., Conclusions: The type of prosthesis material did not influence misfit detection at the IAJ with PERI; however, ZIR had lower diagnostic accuracy than TIT and MC implant-supported crowns with CBCT., (Copyright © 2020 Editorial Council for the Journal of Prosthetic Dentistry. Published by Elsevier Inc. All rights reserved.)

Background: Teaching based on virtual reality simulators in medicine has expanded in recent years due to the limitations of more traditional methods, especially for surgical procedures such as laparoscopy., Purpose of Review: To analyze the effects of using virtual reality simulations on the development of laparoscopic skills in medical students and physicians., Data Sources: The literature screening was done in April 2020 through Medline (PubMed), EMBASE and Database of the National Institute of Health., Eligibility Criteria: Randomized clinical trials that subjected medical students and physicians to training in laparoscopic skills in virtual reality simulators., Study Appraisal: Paired reviewers independently identified 1529 articles and included 7 trials that met the eligibility criteria., Findings: In all studies, participants that trained in virtual simulators showed improvements in laparoscopic skills, although the articles that also had a physical model training group did not show better performance of one model compared to the other., Limitations: No article beyond 2015 met the eligibility criteria, and the analyzed simulators have different versions and models, which might impact the results., Conclusion: Virtual reality simulators are useful educational tools, but do not show proven significant advantages over traditional models. The lack of standardization and a scarcity of articles makes comparative analysis between simulators difficult, requiring more research in the area, according to the model suggested in this review., Systematic Review Registration Number: Registered by the Prospective Register of Systematic Reviews (PROSPERO), identification code CRD42020176479., Competing Interests: The authors have declared that no competing interests exist.

Background: The Family Health Strategy (FHS) became consolidated as a primary care model and gatekeeper for the Unified Health System (Sistema Único de Saúde, SUS) in the Brazil and it is considered one of the largest primary health care programmes in the world. Its rapid expansion allowed the SUS to meet the changing health care needs of the population remote localities of Brazilian municipalities., Methods: In the present study, exploratory data analysis was performed using modelling to provide a general overview of the study and to delineate possible structural characteristics of the cross-sectional time-series data. Panel regression methods were used to assess the association between FHS coverage and ambulatory care-sensitive hospitalizations (ACSH rates) in the municipalities of Pará, in the Brazilian Amazon, from 2008 to 2017., Results: The results showed strong evidence for the association between FHS coverage and ACSH rates, including reductions of 22% in preventable hospitalizations and 15% in hospital expenses that were directly linked to the 40% increase in FHS population coverage during the evaluated period. This expansion of primary care has mainly benefitted areas that are difficult to access and populations that were previously deprived of health care in the vast Amazon territory., Conclusions: The findings of this study show that the increase of the expansion of primary care reduces the preventable hospitalization and the hospital expenses. This reinforces the need for public protection of the health of populations at risk and the positive impacts of primary care in the Brazilian Amazon., Competing Interests: The authors have declared that no competing interests exist.

Purpose: Purpose: To assess the association of various factors including education level and oral health with type 2 diabetics' awareness of periodontitis and periodontitis/diabetes relationship, and to evaluate the importance of integrated healthcare in this association. Materials and Methods: 288 type 2 diabetics were evaluated through a validated structured questionnaire about oral hygiene habits, access and attendance to dental treatment, the presence of periodontitis and previously received information of periodontitis and periodontitis/diabetes relationship. Descriptive data were explored and both simple and multiple logistic regressions were performed. Results: The average age of participants was 62.24 (±10.93) years, 81.6% were previously treated for periodontitis and approximately 70% have never received information on periodontitis and its relationship with diabetes. A higher chance of participants having previously received information regarding periodontitis was associated with more than 8 years of schooling, daily flossing habit, presence of periodontitis and prior treatment for periodontitis (p < 0.005). Regarding previously received information about periodontitis/diabetes relationship, statistically significant associations were observed for more than 12 years of schooling and diabetes diagnosed more than 8 years ago (p < 0.05). Conclusion: The vast majority of participants were previously treated for periodontitis without receiving proper oral health education, which means that access to costly dental treatment is provided while patient education is neglected. It was shown the influence of habits and living conditions on the previously received information about diseases, and therefore, particular attention to the population characteristics is important to make the information accessible to everyone.

Background: The performance of the microbiota is observed in several digestive tract diseases. Therefore, reaching the biliary microbiota may suggest ways for studies of biomarkers, diagnoses, tests and therapies in hepatobiliopancreatic diseases., Methods: Bile samples will be collected in endoscopic retrograde cholangiopancreatography patients (case group) and living liver transplantation donors (control group). We will characterize the microbiome based on two types of sequence data: the V3/V4 regions of the 16S ribosomal RNA (rRNA) gene and total shotgun DNA. For 16S sequencing data a standard 16S processing pipeline based on the Amplicon Sequence Variant concept and the qiime2 software package will be employed; for shotgun data, for each sample we will assemble the reads and obtain and analyze metagenome-assembled genomes., Results: The primary expected results of the study is to characterize the specific composition of the biliary microbiota in situations of disease and health. In addition, it seeks to demonstrate the existence of changes in the case of illness and also possible disease biomarkers, diagnosis, interventions and therapies in hepatobiliopancreatic diseases., Trial Registration: NCT04391426. Registered 18 May 2020, https://clinicaltrials.gov/ct2/show/NCT04391426., Competing Interests: The authors have declared that no competing interests exist.

Invasive species represent a serious ecological threat for many ecosystems worldwide and provide a unique opportunity to investigate rapid adaptation and evolution. Genetic variation allows populations of organisms to be both robust and adaptable to different environmental conditions over evolutionary timeframes. In contrast, invasive animals can rapidly adapt to new environments, with minimal genetic diversity. Thus, the extent to which environmental effects can trigger epigenetic responses is particularly interesting for understanding the role of epigenetics in rapid adaptation. In this review, we provide a brief overview of the different epigenetic mechanisms that control gene expression, and emphasize the importance of epigenetics for environmental adaptation. We also discuss recent publications that provide important examples for the role of epigenetic mechanisms in environmental adaptation. Furthermore, we present an overview of the current knowledge about epigenetic modulation as an adaptive strategy for invasive species. A particularly interesting example is provided by the marbled crayfish, a novel, monoclonal freshwater crayfish species that has colonized diverse habitats within a few years. Finally, we address important limitations of current approaches and highlight the potential importance of less well-known mechanisms for non-genetic organismal adaptation., (© The Author(s) 2020. Published by Oxford University Press on behalf of the Society for Integrative and Comparative Biology.)

Purpose: To assess the accuracy of three cone beam computed tomography (CBCT) systems in misfit detection at the implant-abutment joint., Materials and Methods: A total of 32 implants were placed in dry human mandibles. Porcelain-fused-to-metal crowns, both with and without a 200-μm-thick gap at the implant-abutment joint, were placed and then scanned using three CBCT systems: Picasso Trio (PT), OP300 (OP), and Scanora 3D (SC). Images were assessed, and area under the receiver operating characteristic curve (Az) values were compared (a = .05)., Results: Az values obtained with PT (0.86) were significantly higher than with OP (0.63) and SC (0.64) (P < .05)., Conclusion: Images acquired with PT allowed for more accurate misfit detection at the implant-abutment joint due to higher contrast resolution.

Background: The marbled crayfish (Procambarus virginalis) is a monoclonal, parthenogenetically reproducing freshwater crayfish species that has formed multiple stable populations worldwide. Madagascar hosts a particularly large and rapidly expanding colony of marbled crayfish in a unique environment characterized by a very high degree of ecological diversity., Results: Here we provide a detailed characterization of five marbled crayfish populations in Madagascar and their habitats. Our data show that the animals can tolerate a wide range of ecological parameters, consistent with their invasive potential. While we detected marbled crayfish in sympatry with endemic crayfish species, we found no evidence for the transmission of the crayfish plague pathogen, a potentially devastating oomycete. Furthermore, our results also suggest that marbled crayfish are active predators of the freshwater snails that function as intermediate hosts for human schistosomiasis. Finally, we document fishing, farming and market sales of marbled crayfish in Madagascar., Conclusions: Our results provide a paradigm for the complex network of factors that promotes the invasive spread of marbled crayfish. The commercial value of the animals is likely to result in further anthropogenic distribution.

Background: The possibility of emergence of praziquantel-resistant Schistosoma parasites and the lack of other effective drugs demand the discovery of new schistosomicidal agents. In this context the study of compounds that target histone-modifying enzymes is extremely promising. Our aim was to investigate the effect of inhibition of EZH2, a histone methyltransferase that is involved in chromatin remodeling processes and gene expression control; we tested different developmental forms of Schistosoma mansoni using GKS343, a selective inhibitor of EZH2 in human cells., Methodology/principal Findings: Adult male and female worms and schistosomula were treated with different concentrations of GSK343 for up to two days in vitro. Western blotting showed a decrease in the H3K27me3 histone mark in all three developmental forms. Motility, mortality, pairing and egg laying were employed as schistosomicidal parameters for adult worms. Schistosomula viability was evaluated with propidium iodide staining and ATP quantification. Adult worms showed decreased motility when exposed to GSK343. Also, an approximate 40% reduction of egg laying by GSK343-treated females was observed when compared with controls (0.1% DMSO). Scanning electron microscopy showed the formation of bulges and bubbles throughout the dorsal region of GSK343-treated adult worms. In schistosomula the body was extremely contracted with the presence of numerous folds, and growth was markedly slowed. RNA-seq was applied to identify the metabolic pathways affected by GSK343 sublethal doses. GSK343-treated adult worms showed significantly altered expression of genes related to transmembrane transport, cellular homeostasis and egg development. In females, genes related to DNA replication and noncoding RNA metabolism processes were downregulated. Schistosomula showed altered expression of genes related to cell adhesion and membrane synthesis pathways., Conclusions/significance: The results indicated that GSK343 presents in vitro activities against S. mansoni, and the characterization of EZH2 as a new potential molecular target establishes EZH2 inhibitors as part of a promising new group of compounds that could be used for the development of schistosomicidal agents., Competing Interests: The authors have declared that no competing interests exist.

Background: The parthenogenetic marbled crayfish (Procambarus virginalis) is a novel species that has rapidly invaded and colonized various different habitats. Adaptation to different environments appears to be independent of the selection of genetic variants, but epigenetic programming of the marbled crayfish genome remains to be understood., Results: Here, we provide a comprehensive analysis of DNA methylation in marbled crayfish. Whole-genome bisulfite sequencing of multiple replicates and different tissues revealed a methylation pattern that is characterized by gene body methylation of housekeeping genes. Interestingly, this pattern was largely tissue invariant, suggesting a function that is unrelated to cell fate specification. Indeed, integrative analysis of DNA methylation, chromatin accessibility and mRNA expression patterns revealed that gene body methylation correlated with limited chromatin accessibility and stable gene expression, while low-methylated genes often resided in chromatin with higher accessibility and showed increased expression variation. Interestingly, marbled crayfish also showed reduced gene body methylation and higher gene expression variability when compared with their noninvasive mother species, Procambarus fallax., Conclusions: Our results provide novel insights into invertebrate gene body methylation and its potential role in adaptive gene regulation.

In chronic schistosomiasis, liver fibrosis is linked to portal hypertension, which is a condition associated with high mortality and morbidity. High mobility group box 1 (HMGB1) was originally described as a nuclear protein that functions as a structural co-factor in transcriptional regulation. However, HMGB1 can also be secreted into the extracellular milieu under appropriate signal stimulation. Extracellular HMGB1 acts as a multifunctional cytokine that contributes to infection, injury, inflammation, and immune responses by binding to specific cell-surface receptors. HMGB1 is involved in fibrotic diseases. From a clinical perspective, HMGB1 inhibition may represent a promising therapeutic approach for treating tissue fibrosis. In this study, we demonstrate elevated levels of HMGB1 in the sera in experimental mice or in patients with schistosomiasis. Using immunohistochemistry, we demonstrated that HMGB1 trafficking in the hepatocytes of mice suffering from acute schistosomiasis was inhibited by Glycyrrhizin, a well-known HMGB1 direct inhibitor, as well as by DIC, a novel and potential anti-HMGB1 compound. HMGB1 inhibition led to significant downregulation of IL-6, IL4, IL-5, IL-13, IL-17A, which are involved in the exacerbation of the immune response and liver fibrogenesis. Importantly, infected mice that were treated with DIC or GZR to inhibit HMGB1 pro-inflammatory activity showed a significant increase in survival and a reduction of over 50% in the area of liver fibrosis. Taken together, our findings indicate that HMGB1 is a key mediator of schistosomotic granuloma formation and liver fibrosis and may represent an outstanding target for the treatment of schistosomiasis.

High-mobility group B (HMGB) proteins have highly conserved, unique DNA-binding domains, HMG boxes, that can bind non-B-type DNA structures, such as bent, kinked and unwound structures, with high affinity. HMGB proteins also promote DNA bending, looping and unwinding. In this study, we determined the role of the Aedes aegypti single HMG-box domain protein AaHMGB; characterized its structure, spatiotemporal expression levels, subcellular localization, and nucleic acid binding activities; and compared these properties with those of its double-HMG-box counterpart protein, AaHMGB1. Via qRT-PCR, we showed that AaHMGB is expressed at much higher levels than AaHMGB1 throughout mosquito development. In situ hybridization results suggested a role for AaHMGB and AaHMGB1 during embryogenesis. Immunolocalization in the midgut revealed that AaHMGB is exclusively nuclear. Circular dichroism and fluorescence spectroscopy analyses showed that AaHMGB exhibits common features of α-helical structures and is more stably folded than AaHMGB1, likely due to the presence of one or two HMG boxes. Using several DNA substrates or single-stranded RNAs as probes, we observed significant differences between AaHMGB and AaHMGB1 in terms of their binding patterns, activity and/or specificity. Importantly, we showed that the phosphorylation of AaHMGB plays a critical role in its DNA-binding activity. Our study provides additional insight into the roles of single- versus double-HMG-box-containing proteins in nucleic acid interactions for better understanding of mosquito development, physiology and homeostasis., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Statement of Problem: A misfit or gap at the implant-abutment joint (IAJ) requires detection as it may compromise the health of the peri-implant tissue. However, which radiographic technique provides the most orthogonal relationship between the central beam and the implant/image receptor is unclear., Purpose: The purpose of this in vitro study was to evaluate the diagnostic accuracy of 4 intraoral radiographic techniques on misfit detection at the IAJ., Material and Methods: Twenty implants were placed in polyamide jaws, and customized dental implant abutments with a metal collar were installed. Different gaps were simulated by placing one or three 50-μm-thick polyester strips at the IAJ; the absence of the strip represented the control group (no gap). The 4 radiographic techniques were evaluated by using different film holders: a periapical with bisecting angle (PBA), a bitewing interproximal (BI), a periapical with standard paralleling (PSP), and a periapical with modified paralleling (PMP) holder (with a custom-made paralleling index). A total of 240 digital radiographs were evaluated by 4 clinicians experienced with dental implants. Differences were evaluated by using receiver operating characteristic (ROC) curves (Az) and Fisher tests (α=.05). Diagnostic values (sensitivity, specificity, accuracy, and positive and negative predictive values) were also obtained. The Kappa test was used to assess intra- and interevaluator reproducibility, which ranged from moderate to almost perfect., Results: All diagnostic values, except specificity, were lower for the PBA technique for both the 50- and 150-μm gaps. Az values for the PBA technique were significantly lower than those obtained for the other 3 techniques (P<.05), which did not differ from each other. The 150-μm gaps were more easily detected than the 50-μm gaps only for PBA (P<.05)., Conclusions: The BI, PSP, and PMP techniques detected misfits at the IAJ most accurately. The PBA technique is not recommended for this purpose., (Copyright © 2017 Editorial Council for the Journal of Prosthetic Dentistry. Published by Elsevier Inc. All rights reserved.)

Objectives: Varicella is a disease with potentially severe complications. We aimed to investigate characteristics of hospitalized children with varicella in Brazil in the prevaccine period and to identify predictors for requiring intensive care treatment., Methods: A prospective cohort study was conducted from May 2011 to April 2014. Patients up to 13 years of age with varicella diagnosis were included. Information was collected through interview and review of medical records. Logistic regression analysis was performed., Results: A total of 669 patients were admitted. The median age of subjects was 2.7 years (range 0-14 years) with a predominance of boys (56.6%). The main causes of hospitalization were bacterial complications (77.7%), viral complications (11.4%), and at-risk patients (10.9%). Main bacterial complications were skin infection and pneumonia. Main viral complications were herpes zoster, cerebellitis, and encephalitis. Most at-risk patients used corticosteroids or had a diagnosis of leukemia. At-risk patients were hospitalized earlier ( P < .01) and remained hospitalized for longer periods ( P = .03). A total of 44 patients (6.6%) were admitted to the ICU, and 5 (0.8%) died of septic shock. Thrombocytopenia was associated with more severe illness in patients with bacterial infections ( P = .001). The long-time interval between onset of infection and admission was associated with the need for intensive care in all groups ( P = .007)., Conclusions: Secondary bacterial infection is the main cause of hospitalization, and thrombocytopenia in these patients leads to worse outcomes. Difficulties of access to the health system and delay in medical care are determining factors of greater severity in this population., Competing Interests: POTENTIAL CONFLICT OF INTEREST: The authors have indicated they have no potential conflicts of interest to disclose., (Copyright © 2018 by the American Academy of Pediatrics.)

Periodontitis is associated with reduced antioxidant capacity and increased oxidative damage. Oxidative stress induces inflammation and bone loss contributing to the pathological progression of periodontal disease. Calendula officinalis (CLO) has demonstrated anti-inflammatory and anti-oxidant activities. Therefore, the aim of this study was to evaluate the effect of CLO on oxidative stress and bone loss in rats subjected to experimental periodontitis (EP). For this, 72 male Wistar rats were divided into groups: Naïve, Saline (SAL) and CLO. Rats received SAL or CLO (90 mg/kg) 30 min before ligature and daily until the 11th day. Naïve group experienced no manipulation. After 11 days, the animals were euthanized and left maxillae collected for macroscopic analysis of alveolar bone loss (ABL). Periodontium was analyzed by macroscopy, scanning electron microscopy; confocal and light polarized microscopy. Immunohistochemical examination of DKK1, WNT 10b and β-catenin was performed. The gingival tissue was collected to reduced glutathione (GSH), superoxide dismutase (SOD), catalase (CAT) and malondialdehyde (MDA) analyses. The 11 days of ligature induced bone loss, breakdown of collagen fibers, increased the immunostaining DKK-1 while reduced WNT 10b and β-catenin expressions. Periodontitis reduced GSH, SOD, CAT and increase MDA. All findings were reversed by 90 mg/kg of CLO. In summary our findings demonstrated that CLO reduced oxidative stress and bone loss and preserved collagen fibers in rats with EP, with participation of WNT signaling pathway.

High Mobility Group protein 1 (HMGB1) is a non-histone, chromatin-associated nuclear protein that functions in regulating eukaryotic gene expression. We investigated the influence and mechanism of action of Aedes aegypti HMGB1 (AaHMGB1) on mosquito Rel1A-mediated transcription from target gene promoters. The DNA-binding domain (RHD) of AaRel1A was bacterially expressed and purified, and AaHMGB1 dramatically enhanced RHD binding to consensus NF-kB/Rel DNA response elements. Luciferase reporter analyses using a cecropin gene promoter showed that AaHMGB1 potentiates the transcriptional activity of AaRel1A in Aag-2 cells. Moreover, overexpression of AaHMGB1 in Aag-2 cells led to an increase in mRNA levels of antimicrobial peptide genes. In vitro GST pull-down assays revealed that the presence of DNA is a pre-requisite for assembly of a possible ternary complex containing DNA, AaHMGB1 and AaRel1A. Notably, DNA bending by AaHMGB1 enhanced the binding of AaRel1A to a DNA fragment containing a putative NF-kB/Rel response element. Importantly, AaHMGB1 was identified as a potential immune modulator in A. aegypti through AaHMGB1 overexpression or RNAi silencing in Aag-2 cells followed by bacterial challenge or through AaHMGB1 RNAi knockdown in mosquitoes followed by Dengue virus (DENV) infection. We propose a model in which AaHMGB1 bends NF-kB/Rel target DNA to recruit and allow more efficient AaRel1A binding to activate transcription of effector genes, culminating in a stronger Toll pathway-mediated response against DENV infection., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Aedes aegypti mosquitoes are important vectors of viral diseases. Mosquito host factors play key roles in virus control and it has been suggested that dengue virus replication is regulated by Dnmt2-mediated DNA methylation. However, recent studies have shown that Dnmt2 is a tRNA methyltransferase and that Dnmt2-dependent methylomes lack defined DNA methylation patterns, thus necessitating a systematic re-evaluation of the mosquito genome methylation status. We have now searched the Ae. aegypti genome for candidate DNA modification enzymes. This failed to reveal any known (cytosine-5) DNA methyltransferases, but identified homologues for the Dnmt2 tRNA methyltransferase, the Mettl4 (adenine-6) DNA methyltransferase, and the Tet DNA demethylase. All genes were expressed at variable levels throughout mosquito development. Mass spectrometry demonstrated that DNA methylation levels were several orders of magnitude below the levels that are usually detected in organisms with DNA methylation-dependent epigenetic regulation. Furthermore, whole-genome bisulfite sequencing failed to reveal any evidence of defined DNA methylation patterns. These results suggest that the Ae. aegypti genome is unmethylated. Interestingly, additional RNA bisulfite sequencing provided first evidence for Dnmt2-mediated tRNA methylation in mosquitoes. These findings have important implications for understanding the mechanism of Dnmt2-dependent virus regulation.

Chronic chagasic cardiomyopathy (CCC) develops years after acute infection by Trypanosoma cruzi and does not improve after trypanocidal therapy, despite reduction of parasite burden. During disease, the heart undergoes oxidative stress, a potential causative factor for arrhythmias and contractile dysfunction. Here we tested whether antioxidants/ cardioprotective drugs could improve cardiac function in established Chagas heart disease. We chose a model that resembles B1-B2 stage of human CCC, treated mice with resveratrol and performed electrocardiography and echocardiography studies. Resveratrol reduced the prolonged PR and QTc intervals, increased heart rates and reversed sinus arrhythmia, atrial and atrioventricular conduction disorders; restored a normal left ventricular ejection fraction, improved stroke volume and cardiac output. Resveratrol activated the AMPK-pathway and reduced both ROS production and heart parasite burden, without interfering with vascularization or myocarditis intensity. Resveratrol was even capable of improving heart function of infected mice when treatment was started late after infection, while trypanocidal drug benznidazole failed. We attempted to mimic resveratrol's actions using metformin (AMPK-activator) or tempol (SOD-mimetic). Metformin and tempol mimicked the beneficial effects of resveratrol on heart function and decreased lipid peroxidation, but did not alter parasite burden. These results indicate that AMPK activation and ROS neutralization are key strategies to induce tolerance to Chagas heart disease. Despite all tissue damage observed in established Chagas heart disease, we found that a physiological dysfunction can still be reversed by treatment with resveratrol, metformin and tempol, resulting in improved heart function and representing a starting point to develop innovative therapies in CCC., Competing Interests: The authors have declared no competing interests exist.

The Schistosoma mansoni High Mobility Group Box (HMGB) proteins SmHMGB1, SmHMGB2 and SmHMGB3 share highly conserved HMG box DNA binding domains but have significantly different C-terminal acidic tails. Here, we used three full-length and tailless forms of the S. mansoni HMGB proteins to examine the functional roles of their acidic tails. DNA binding assays revealed that the different lengths of the acidic tails among the three SmHMGB proteins significantly and distinctively influenced their DNA transactions. Spectroscopic analyses indicated that the longest acidic tail of SmHMGB3 contributes to the structural stabilisation of this protein. Using immunohistochemical analysis, we showed distinct patterns of SmHMGB1, SmHMGB2 and SmHMGB3 expression in different tissues of adult worms. RNA interference approaches indicated a role for SmHMGB2 and SmHMGB3 in the reproductive system of female worms, whereas for SmHMGB1 no clear phenotype was observed. Schistosome HMGB proteins can be phosphorylated, acetylated and methylated. Importantly, the acetylation and methylation of schistosome HMGBs were greatly enhanced upon removal of the acidic tail. These data support the notion that the C-terminal acidic tails dictate the differences in the structure, expression and function of schistosome HMGB proteins., (Copyright © 2016 Australian Society for Parasitology Inc. Published by Elsevier Ltd. All rights reserved.)

Manufacturing and marketing of mineral mixtures with less than 40 g kg(-1) phosphorus (P) is prohibited under Brazilian regulations, although scientific evidence rejects this recommendation. Considering the hypothesis that P levels in commercial mineral supplements can be reduced without affecting animal performance and health, the objective of this experiment was to evaluate the effects of reducing the concentration of P in the mineral supplement (from 40 to 18 g kg(-1)) of a herd of beef cows grazing tropical pastures of signal grass (Urochloa decumbens). The experiment was carried out in the savanna region of Mato Grosso do Sul, Brazil, during the years 2011 to 2013. Variables analyzed included pregnancy rate, calving interval, weight of calves at weaning, and cost of mineral supplementation. There were no changes in the reproductive parameters of the herd and the weight at weaning of the calves. However, the cost of mineral supplementation was significantly lower when the herd was supplemented with the mineral mix containing only 18 g kg(-1) P. Phosphorus concentration of the forage was analyzed monthly during 1 year and averaged 1.9 ± 0.45 g kg(-1) DM. Thus, it appears possible to reduce P content and cost of mineral supplementation without any adverse effects on the health and productivity of beef cattle herds in the State of Mato Grosso do Sul. However, the final decision should be made based on the clinical-nutritional examination and by constant technical assistance to the farm.

Antimicrobial resistance in Escherichia coli isolated from pet dogs can be considered a potential threat of infection for the human population. Our objective was to characterize the resistance pattern, extended spectrum beta-lactamase production and genetic relatedness of multiresistant E. coli strains isolated from dogs (n=134), their owners (n=134), and humans who claim to have no contact with dogs (n=44, control), searching for sharing of strains. The strains were assessed for their genetic relatedness by phylogenetic grouping and pulsed-field gel electrophoresis. Multiresistant E. coli strains were isolated from 42 (31.3%) fecal samples from pairs of dogs and owners, totaling 84 isolates, and from 19 (43.1%) control group subjects. The strains showed high levels of resistance to ampicillin, streptomycin, tetracycline, trimethoprim and sulfamethoxazole regardless of host species or group of origin. The blaTEM, blaCTX-M, and blaSHV genes were detected in similar proportions in all groups. All isolates positive for bla genes were ESBL producers. The phylogenetic group A was the most prevalent, irrespective of the host species. None of the strains belonging to the B2 group contained bla genes. Similar resistance patterns were found for strains from dogs, owners and controls; furthermore, identical PFGE profiles were detected in four (9.5%) isolate pairs from dogs and owners, denoting the sharing of strains. Pet dogs were shown to be a potential household source of multiresistant E. coli strains., (Copyright © 2016 Sociedade Brasileira de Microbiologia. Published by Elsevier Editora Ltda. All rights reserved.)

Objective: We investigated the anti-inflammatory activity of strontium ranelate (SR) in arthritis models., Materials and Methods: Rats received 1 mg zymosan (Zy) or saline intra-articularly. Other groups were subjected to anterior cruciate ligament transection in the right knee, as an osteoarthritis (OA) model, or a sham procedure. Joint pain was assessed using the articular incapacitation and paw-pressure tests. Cell influx and cytokines were measured in joint exudates., Treatment: Groups received either SR (30-300 mg/kg per os) or saline., Results: SR dose-dependently and significantly inhibited joint pain in both Zy and OA models, while not altering cell influx. Naloxone administration significantly reversed SR analgesia. SR significantly reduced levels of Interleukin-1β and tumor necrosis factor-α in Zy arthritis, whereas those of cytokine-induced neutrophil chemoattractant (CINC)-1 were not altered., Conclusions: SR provides analgesia in arthritis that is associated to inhibition of the release of inflammatory cytokines into inflamed joints. This effect is abrogated by administration of the opioid antagonist naloxone.

Objective: to describe the causes and severities of trauma in patients who met the criteria for alcohol abuse or dependence according to Mini International Neuropsychiatric Interview, and to display the pattern of alcohol consumption and subsequent changes one year after trauma., Methods: a transversal and longitudinal quantitative study carried out between November 2012 and September 2013 in the ED. Medical and nursing students collected blood samples, applied the J section of the Mini International Neuropsychiatric Interview (MINI) and submitted alcohol abusers and dependents to BI. One year after admission, patients were contacted and asked about their patterns of alcohol use and their reasons for any changes., Results: from a sample of 507 patients admitted to the ED for trauma, 348 responded to MINI, 90 (25.9%) being abusers and 36 (10.3%) dependent on alcohol. Among the abusers, the most frequent cause of injury was motorcycle accident (35.6%) and among the dependents it was predominantly interpersonal violence (22.2%). Positive blood samples for alcohol were identified in 31.7% of the abusers and 53.1% of the dependents. One year after trauma, 66 abusers and 31 dependents were contacted, and it was ascertained that 36.4% of the abusers and 19.4% of the dependents had decreased alcohol consumption. The main reported reason for the reduction was the experienced trauma., Conclusion: the motorcycle accident was the most common cause of injury. The detection of problematic alcohol use and implementation of BI are important strategies in the ED, however for alcohol abusers and dependents, BI was not the most reported reason for any changes in patterns of alcohol use.

Purpose: To evaluate the effects of preconditioning with oils mixes containing ω3/ω6/ω9 associated with micro-currents on skin repair in rats., Methods: One-hundred and eight Wistar rats randomized into G-1, G-2 and G-3 groups were treated with saline (0.9%), mix 1 (corn+soybean oils) and mix 2 (olive+canola+flaxseed oils), respectively, in a single dose (0.01ml/g) by gavage. Next, each group was subdivided into sham and stimulated subgroups. Pulsed-wave microcurrents (0.5 µA, 0.5 Hz) were applied to stimulated subgroups for 20 min. One hour later anesthetized rats were subjected to surgery. A dorsal incision (6 cm long) was carried out and closed with interrupted nylon sutures. Samples (1 cm2) were harvested from the mid-portion of the incision on the 7, 14, 21 post-operative (P.O.) days. Variables were analyzed using Mann-Whitney/Dunn tests Significance level was set to 5 % (p<0.05)., Results: Micro-currents promoted increase of exudate and reduction of epithelialization on day 7 in G1 rats. Mixes 1/2 reduced vascularization on 7/14th days P.O. Both 1/2 mixes reduced fibrosis on day 14. Preconditioning with mix 1 led to increased expression of NF-kB on the 7th day., Conclusion: Preconditioning with microcurrents has pro-inflammatory effects while oil mixes 1 and 2 decrease fibrosis and vascularization in the proliferative phase of cicatrization.