Genetic polymorphisms associated with developmental defects of enamel: A systematic review.

BACKGROUND: Polymorphisms in genes related to enamel formation and mineralization may increase the risk of developmental defects of enamel (DDE). AIM: To evaluate the existing literature on genetic polymorphisms associated with DDE. DESIGN: This systematic review was registered in the PROSPERO (CRD42018115270). The literature search was performed in PubMed, Scopus, Web of Science, LILACS, BBO, Cochrane Library, and in the gray literature. Observational studies assessing the association between DDE and genetic polymorphism were included. The Newcastle-Ottawa Scale was used to assess the risk of bias. RESULTS: One thousand one hundred and forty-six articles were identified, and 28 met the inclusion criteria. Five studies presented a low risk of bias. Ninety-two genes related to enamel development, craniofacial patterning morphogenesis, immune response, and hormone transcription/reception were included. Molar-incisor hypomineralization (MIH) and/or hypomineralization of primary second molars (HPSM) were associated with 80 polymorphisms of genes responsible for enamel development, immune response, morphogenesis, and xenobiotic detoxication. A significant association was found between the different clinical manifestations of dental fluorosis (DF) with nine polymorphisms of genes responsible for enamel development, craniofacial development, hormonal transcription/reception, and oxidative stress. Hypoplasia was associated with polymorphisms located in intronic regions. CONCLUSION: MIH, HPSM, DF, and hypoplasia reported as having a complex etiology are significantly associated with genetic polymorphisms of several genes.

Which are the clinical consequences of Molar Incisor hypomineralization (MIH) in children and adolescents? Systematic review and meta-analysis.

OBJECTIVE: This systematic review was conducted to address the following research question: "What are the clinical consequences (outcome) of Molar Incisor Hypomineralization (MIH) (exposure) in children and adolescents (population/patient)?". MATERIAL AND METHODS: After defining the strategy, a search was performed in different databases (MEDLINE via Pubmed, Cochrane Library, BBO, LILACS, Scopus, Web of Science, Embase) and Grey literature in August 2023. Cross-sectional observational studies that identified clinical consequences of MIH (dental caries, post-eruptive structural loss, atypical restorations, hypersensitivity and tooth extraction) were included. The risk of bias was assessed following the Joanna Briggs Institute protocol for cross-sectional studies. Meta-analyses were conducted for each outcome, taking into account the number of patients and teeth. The effect measure considered was the prevalence; random-effects model was adopted. Heterogeneity was assessed using I2 statistics and prediction intervals (PI). RESULTS: A total of 903 studies were identified; 41 were selected for qualitative analysis and 38 for quantitative analysis. Twenty eight studies were classified as presenting uncertain risk of bias, 11 as low risk and 3 as high risk of bias. The prevalence levels, ranked from highest to lowest and considering the tooth and patient units, respectively, were: caries lesions (0.252 - 95% CI 0.158-0.375; 0.512 - 95% CI 0.385-0.639); hypersensitivity (0.286 - 95% CI 0.190-0.407; 0.417 - 95% CI 0.197-0.674), post-eruptive fracture (0.125 - 95% CI 0.099-0.158; 0.257 - 95% CI 0.145-0.412); atypical restorations (0.048 - 95% CI 0.030-0.077; 0.167 - 95% CI 0.096 - 0.274); tooth extraction (0.012 - 95% CI 0.007-0.019; 0.090 - 95% CI 0.019 - 0.331). All meta-analyses resulted in heterogeneity greater than 85%, with the exception of the outcome "tooth extraction" according to the tooth unit (I2 = 57.83). This heterogeneity may be attributed to factors such as differences in the location where the study was realized, the socioeconomic conditions of the studied population, the asymmetric nature of MIH, and patient age. CONCLUSION: The most common consequences of MIH are caries lesions, hypersensitivity, and post-eruptive breakdown. (PROSPERO:CRD42020201410).

Analysis of the indications for and results of breast cancer screening by magnetic resonance imaging at a cancer center in Brazil.

Objective: To evaluate the indications for and results of magnetic resonance imaging (MRI) examinations for breast cancer screening at a cancer center in Brazil. Materials and Methods: This was a retrospective observational study, based on electronic medical records, of patients undergoing MRI for breast cancer screening at a cancer center in Brazil. Results: We included 597 patients between 19 and 82 years of age. The main indications for MRI screening were a personal history of breast cancer, in 354 patients (59.3%), a family history of breast cancer, in 102 (17.1%), and a confirmed genetic mutation, in 67 (11.2%). The MRI result was classified, in accordance with the categories defined in the Breast Imaging Reporting and Data System, as benign (category 1 or 2), in 425 patients (71.2%), probably benign (category 3), in 143 (24.0%), or suspicious (category 4 or 5), in 29 (4.9%). On MRI, 11 malignant tumors were identified, all of which were invasive carcinomas. Among those 11 carcinomas, six (54.5%) were categorized as minimal cancers (< 1 cm), and the axillary lymph nodes were negative in 10 (90.9%). The cancer detection rate was 18.4/1,000 examinations, and the positive predictive value for suspicious lesions submitted to biopsy was 37.9%. Conclusion: In our sample, the main indication for breast MRI screening was a personal history of breast cancer. The results indicate that MRI is a highly accurate method for the early detection of breast neoplasms in this population.

Objetivo: Avaliar as indicações e resultados de exames de ressonância magnética (RM) para rastreamento de câncer de mama em um centro oncológico no Brasil. Materiais e Métodos: Estudo observacional, realizado mediante análise retrospectiva de pacientes submetidos a RM das mamas para rastreamento de câncer de mama, por meio de revisão do prontuário eletrônico em um centro oncológico. Resultados: Foram incluídas 597 pacientes com idade variando de 19 a 82 anos. As principais indicações para rastreamento foram história pessoal de câncer de mama em 354 (59,3%) pacientes, história familiar em 102 (17,1%) e mutação genética confirmada em 67 (11,2%). O resultado da RM foi benigno (BI-RADS 1 ou 2) em 425 (71,2%) pacientes, provavelmente benigno (BI-RADS 3) em 143 (24,0%) e suspeito (BI-RADS 4 ou 5) em 29 (4,9%). Foram identificados 11 tumores malignos na RM, todos carcinomas invasivos, porcentagem de cânceres "mínimos" (< 1 cm) de 54,5% e porcentagem de axila negativa de 90,9%. A taxa de detecção de câncer na RM foi 18,4/1000 exames e o valor preditivo positivo para as lesões suspeitas submetidas a biópsia foi 37,9%. Conclusão: A principal indicação para RM de rastreamento na nossa população foi história pessoal de câncer de mama. Os resultados mostraram que a RM constitui um método com alta acurácia para detecção precoce de neoplasias da mama nessa população.

Association of defects of enamel with polymorphisms in the vitamin D receptor and parathyroid hormone genes.

This cross-sectional study aimed to investigate the association between developmental defects of enamel (DDE) and single nucleotide polymorphisms (SNPs) in the genes encoding the vitamin D receptor (VDR) and parathyroid hormone (PTH). Orthodontic patients receiving treatment at a dental school were selected through convenience sampling. Intra-oral photographs were used to assess DDE, which were classified according to the criteria proposed by Ghanim et al. (2015) by a single calibrated examiner (Kappa>0.80). Enamel hypoplasia, molar-incisor hypomineralization (MIH), hypomimineralized second primary molar (HSPM), and non-MIH/HSPM demarcated opacities were considered for the analysis. Genomic DNA was extracted from buccal cells. The SNPs in VDR (rs7975232) and PHT (rs694, rs6256, and rs307247) were genotyped using real-time polymerase chain reactions (PCR). Statistical analyses were performed using the PLINK software (version 1.03, designed by Shaun Purcell, EUA). Chi-square or Fisher's exact tests were performed at a significance level of 5%. Ninety-one (n=91) patients (49 females and 42 males) (mean age of 14.1±5.8 years) were included. The frequency of DDE was 38.5% (35 patients). Genotype distributions were in Hardy-Weinberg equilibrium. No significant statistical association was found between DDE and the SNPs evaluated. A borderline association (p=0.09) was observed between DDE and the CC haplotype for SNP rs7975232 in VDR. In conclusion, the selected SNPs in VDR and PTH genes were not associated with DDE in the studied samples.

Examining the Use of VR as a Study Aid for University Students with ADHD.

Attention-deficit/hyperactivity disorder (ADHD) is a neurodevelopmental condition characterized by patterns of inattention and impulsivity, which lead to difficulties maintaining concentration and motivation while completing academic tasks. University settings, characterized by a high student-to-staff ratio, make treatments relying on human monitoring challenging. One potential replacement is Virtual Reality (VR) technology, which has shown potential to enhance learning outcomes and promote flow experience. In this study, we investigate the usage of VR with 27 university students with ADHD in an effort to improve their performance in ctableompleting homework, including an exploration of automated feedback via a technology probe. Quantitative results show significant increases in concentration, motivation, and effort levels during these VR sessions and qualitative data offers insight into considerations like comfort and deployment. Together, the results suggest that VR can be a valuable tool in leveling the playing field for university students with ADHD.

Evolution of mortality rates among women of reproductive age in Brazilian municipalities: an ecological analysis using Global Burden of Disease estimates.

OBJECTIVES: Women's mortality at a reproductive age has been a global concern, and its decrease has been incorporated as a target of the UN Sustainable Development Goals. The aim of this study was to describe the spatial-temporal evolution of mortality rates among women of reproductive age in Brazilian municipalities by groups of causes and socioeconomic indicators from 2000 to 2018. STUDY DESIGN: Ecological analysis. METHODS: This work was an ecological, descriptive study that analyzed estimates of mortality rates among women of reproductive age (15-49 years) by main groups of causes of death from the Global Burden of Disease (GBD) study in three consecutive trienniums, T1 (2000-2002), T2 (2009-2011), and T3 (2016-2018). To quantify the temporal evolution in mortality rates, the present study calculated the percentage change for each triennium. The spatial analysis of mortality rates was carried out using Moran's index. The Pearson coefficient was used to analyze the correlation between the data. RESULTS: A significant decline in mortality rates was found for all groups of causes in all regions of the country. Despite the downward trend, the percentage change from 2009 to 2011 to 2016 to 2018 showed a decrease in the group of Noncommunicable Diseases (NCDs) and external causes. The decline in mortality rates of women due to external causes showed only a minimal change in the North and Northeast regions from T2 to T3, whereas a cluster of neighboring municipalities with high mortality rates persisted in the municipalities of the South region and in the state of Roraima. The ranking of the main causes of death in Brazilian municipalities showed an increase in neoplasms in detriment to cardiovascular diseases (CVDs). CONCLUSIONS: The main causes of death in women of reproductive age at a more local level could be used to recognize inequalities and to develop interventions aimed at tackling premature and preventable deaths.

Cytotoxicity Screening of Sterculia striata A.St.-Hil. & Naudin (Chichá) and Arachis hypogaea L. (Peanut) and Comparative Chemical Profiles Before and After in Vitro Digestion.

This study traced the cytotoxicity, antioxidant activity, and phytochemical profile before and after in vitro digestion of nuts from Sterculia striata A. St.-Hil. & Naudin (Malvaceae) (chichá or monkey's peanut), a native plant from Brazil, in comparison with Arachis hypogaea L. (peanut). The antioxidant activity in the 2,2'-Azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS), 2,2-diphenyl-1-picrylhydrazyl (DPPH), and Ferric Reducing Antioxidant Power Assay (FRAP) assays was lower in chichá when compared with peanuts, corroborating the lower concentration of polyphenols. None of the samples studied showed significant cytotoxicity in 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromideDAD: diode-array detection (MTT) assays. In vitro digestion altered the phytochemical profile in both plants, increasing the concentration of rutin in fresh and roasted chichá but only in raw peanuts. In roasted peanuts, rutin was converted into quercetin. Chichá nuts have been used by the local population for centuries, and the identification of their bioactive components can be useful to promote their benefits as a functional food.

The creation of the Fundação Brasileira para a Conservação da Natureza.

This study within the field of environmental history explores the scenario amid which the Fundação Brasileira para a Conservação da Natureza (Brazilian Foundation for Nature Conservation) was founded between 1958 and 1966; this important Brazilian non-governmental organization headquartered in Rio de Janeiro worked at the local, national, and international levels. Primary documentary sources were utilized, along with research of the related literature. The conclusions demonstrate the importance of non-governmental organizations predating this foundation, and the influence of conservationists on its establishment and current work.

TELEPHYSIOTHERAPY FOR THE TREATMENT OF PHANTOM LIMB PAIN: A QUASI-EXPERIMENTAL STUDY / TELEFISIOTERAPIA PARA O TRATAMENTO DA DOR NO MEMBRO FANTASMA: UM ESTUDO QUASI-EXPERIMENTAL

Background and objective: Phantom Limb Pain (PLP) is a common complication of extremity amputation, with a prevalence between 41% and 46% of cases. Despite its uncertain pathophysiology, evidence suggests multifactorial mechanisms to explain the painful phenomenon, which directly affects the individual's quality of life. The objective of the study was to analyze the effect of a telephysiotherapy protocol for PLP on the quality of life, intensity and perception of pain in individuals with extremity amputees. Method: Quasi-experimental study with a qualitative-quantitative approach, with a sample consisting of nine individuals. The instruments used were the McGill Pain Questionnaire, the Verbal Pain Scale, the Short-Form Health Survey (SF-36) and an assessment form prepared in an interview format, all applied before and after the treatment protocol. The intervention consisted of an adaptation to the Graduated Motor Imagery (GMI) protocol; held online via the GoogleMeet platform. Quantitative analysis was performed using the paired Wilcoxon test for non-parametric variables and Pearson correlation. The qualitative approach was analyzed using the content analysis method. Results: There was no significant difference in quality of life parameters and pain intensity before and after treatment, but there was a significant decrease in the perception of total pain and emotional components, which was also evidenced in the qualitative reports. Conclusion: The adapted IMG protocol significantly reduced the perception of pain, especially in the emotional aspect, without significant results in the intensity of pain and quality of life of the individual.

Justificativa e objetivo: A dor fantasma (DF) é uma complicação comum da amputação de extremidades, com prevalência entre 41% e 46% dos casos. Apesar de sua fisiopatologia incerta, evidências sugerem mecanismos  multifatoriais para explicar o fenômeno doloroso, que afeta diretamente a qualidade de vida do indivíduo. O objetivo do estudo foi analisar o efeito de um protocolo de telefisioterapia para DF na qualidade de vida, intensidade e percepção da dor de indivíduos amputados de extremidades. Método: Estudo quasi-experimental com abordagem quali-quantitativa, com amostra composta por nove indivíduos. Os instrumentos utilizados foram o Questionário de Dor de McGill, a Escala Verbal de Dor (EVD), o Short-Form Health Survey (SF-36) e ficha de avaliação elaborada no formato de entrevista, todos aplicados antes e após o protocolo de tratamento. A intervenção constituiu de uma adaptação ao protocolo de Imagens Motoras Graduadas (IMG); realizado de forma on-line pela plataforma GoogleMeet. A análise quantitativa se deu através do teste de Wilcoxon pareado para variáveis não paramétricas e correlação de Pearson. A abordagem qualitativa foi analisada pelo método de análise de conteúdo. Resultados: Não houve diferença significativa nos parâmetros de qualidade de vida e intensidade da dor pré e pós tratamento, porém houve diminuição significativa da percepção de dor total e nos componentes emocionais, o que também foi evidenciado nos relatos qualitativos. Conclusão: O protocolo adaptado de IMG diminuiu significativamente a percepção de dor, especialmente no aspecto emocional, sem resultados significativos na intensidade da dor e qualidade de vida dos indivíduos.

Dentin hypersensitivity and toothache among patients diagnosed with Molar-Incisor Hypomineralization: A systematic review and meta-analysis.

OBJECTIVES: To determine the prevalence of dentin hypersensitivity (DH) and toothache in patients with Molar-Incisor Hypomineralization (MIH); and evaluate whether patients with MIH have greater likelihood of presenting DH/toothache than controls. DATA: Studies evaluating DH/toothache in patients with MIH were included. Studies focusing on other enamel defects were excluded. SOURCES: Eight databases, including grey literature, were searched in January 2024. STUDY SELECTION: The methodological quality of studies was assessed using the Joanna Briggs Institute checklist for Cross-sectional studies. Proportion and association meta-analyses, subgrouped by diagnostic methods, were conducted. The certainty of evidence was assessed using GRADE approach. RESULTS: Fifteen studies were included in the qualitative analysis and fourteen in the meta-analyses. Two studies fulfilled all items of the methodological quality checklist. The overall prevalence of DH/toothache among patients with MIH was 45 %. Prevalence rates of 30 %, 47 %, and 55 % were estimated based on proxy reports, self-reports, and air stimulation, respectively. The overall prevalence of DH/toothache per tooth was 22 %, ranging from 16 % to 29 % according to the diagnostic method. Patients with MIH demonstrated higher likelihood of presenting proxy reports of DH/toothache compared to those without MIH (OR: 1.51, 95 % CI [1.23-1.85], P < 0.01, I2: 0 %). The certainty of evidence was very low, mainly due to the low methodological quality of included studies and high inconsistency. CONCLUSIONS: The global prevalence of DH/toothache was 22 %, per tooth, and 45 % per patient. Estimates vary according to diagnostic methods. Patients with MIH showed higher likelihood of presenting proxy reports of DH/toothache than controls. CLINICAL SIGNIFICANCE: This systematic review contributes valuable information to the dental literature by assessing the prevalence and associated factors of DH/toothache in patients with MIH. The findings can guide future research, inform clinical practices and public policy makers, and ultimately improve the management of oral health of patients with MIH. REGISTRATION: PROSPERO CRD42023432805.

Can We Use the Maximum Phonation Time as a Screening of Pulmonary Forced Vital Capacity in Post-COVID-19 Syndrome Patients?

OBJECTIVE: To verify the accuracy of the maximum phonation time of the vowel /a/ (MPT/a/), fricative /s/ (MPT/s/), number counting (MPTC), and number reached in this count (CN) to estimate forced vital capacity (FVC) in patients with post-COVID-19 syndrome. METHOD: Cross-sectional study involving adult patients, who were admitted to the intensive care unit and referred to the Post-COVID-19 Rehabilitation Outpatient Clinic. Voice function was assessed using a Vocal Handicap Index (VHI) self-assessment questionnaire and MPT tests. To perform the phonatory tests, the patients remained in a standing posture and were instructed to inhale as much air as possible and, during a single exhalation, at usual pitch and loudness, sustain the emission of /a/ and /s/; and in another breath, to perform the ascending numerical count, starting from the number one up to the highest number they could reach. Pulmonary function was assessed by spirometry. The receiver operating characteristic (ROC) curve was plotted, and FVC values lower than the normal limit by Z-score (fifth percentile) were classified as impaired lung function. The predictive values and likelihood ratios were calculated. RESULTS: A total of 70 patients participated, with 20-30% having a high VHI. Approximately 24% had an FVC impairment and significantly low values of MPT/a/, MPT/s/, MPTC, and CN. The test results showed overall accuracy of 70% and the cutoff points of 9.69, 6.78, 10.60, and 13, respectively, with high sensitivity, predictive negative value and low specificity, predictive positive value, and positive likelihood ratio. CONCLUSIONS: Our results suggest that the MPT has moderate discriminatory power for FVC impairment, indicating that it is not a reliable indicator of pulmonary function in the population studied. Therefore, in patients with an MPT of less than 10.60 seconds, or a CN lower than 13, other criteria should be added to improve the diagnostic accuracy and support the decision to perform more complex investigations.

Association between dental age and malocclusions: a systematic review.

BACKGROUND: The evidence in the literature suggests that some skeletal or dental malocclusions are involved with dental development, resulting in advanced or delayed dental age (DA). The purpose of this systematic review was to investigate the association between DA and different types of malocclusions. METHODS: The search was carried out on PubMed, Scopus, Web of Science, Virtual Health Library, and in the gray literature. Observational studies that evaluated the association between DA and sagittal, vertical, or transversal malocclusions were included. The quality assessment was performed using the Newcastle-Ottawa Scale (NOS). The data from primary studies were narratively synthesized. The certainty of evidence was evaluated using the GRADE approach. The study was conducted from August 2023 to October 2023. RESULTS: One Thousand Nine Hundred Ninety-One records were identified in the initial search. Twenty (n = 20) studies were included. Most of the studies (n=15) presented a moderate quality according to NOS. Twelve studies evaluated the association between DA and sagittal discrepancies; eight studies evaluated vertical discrepancies, and only one study analyzed a transversal discrepancy. Demirjian's method for DA assessment was the most used among the studies. The primary studies observed that patients of both sexes presenting a vertical growth pattern and males with skeletal Class III malocclusion tend to have advanced DA. The study that investigated transversal malocclusion found that unilateral posterior cross-bite is associated with delayed DA. The certainty of evidence was very low for all outcomes evaluated. CONCLUSION: DA may be associated with the type of malocclusion. It is suggested that DA can be used as an initial diagnostic tool in orthodontics. Future well-designed studies should be performed in order to investigate the association between DA and different types of malocclusions in more detail. TRIAL REGISTRATION: This study was registered in the PROSPERO database (CRD42023454207).

Pediatric Asthma Therapy Assessment Questionnaire for the Brazilian population: Cross-cultural adaptation and measurement properties.

OBJECTIVE: To cross-culturally adapt the Pediatric Asthma Therapy Assessment Questionnaire (ATAQ) into Brazilian Portuguese and analyze its measurement properties. METHODS: This exploratory methodological study included eight experts and 30 caregivers in the translation and cross-cultural adaptation steps. Thereafter, 118 caregivers of pediatric patients with asthma aged between 5 and 17 years were involved in the analysis of measurement properties. We analyzed the content, structural (exploratory and confirmatory factorial), construct (convergent and discriminant), and known-groups validities; floor and ceiling effects; and determined the cut-off point (receiver operator characteristic curve) to identify pediatric patients with uncontrolled asthma. Intraclass correlation coefficient (ICC) analyzed test-retest reliability with 54 caregivers, whereas Cronbach's α and composite reliability verified the internal consistency of the items. RESULTS: The committee of experts and caregivers found the instructions and response options relevant, understandable, and clear (K > 0.75). During the cross-cultural adaptation, three items (2, 4, and 12) were slightly modified by including terms to facilitate understanding. A two-factor structure (asthma control and patient-provider communication) was identified. Internal consistency (α > .67; composite reliability > 0.73) and test-retest reliability (ICC > 0.80) were acceptable. For construct and know-groups validities, 85.71% of the hypothesis were confirmed. A cut-off point of >3 for the control domain was considered adequate to identify pediatric patients with uncontrolled asthma (sensitivity: 86.21%; specificity: 80.90%). CONCLUSION: The Pediatric ATAQ was adequately adapted for Brazilian pediatric patients with asthma and produced valid and reliable measures for assessing asthma control. Therefore, it may be considered an adequate instrument for monitoring asthma control in the Brazilian pediatric population.

Maximum Phonation Times as Biomarkers of Lung Function.

PURPOSE: To verify whether measurements of maximal phonation times are biomarkers of forced vital capacity in patients with chronic obstructive pulmonary disease, and to characterize the vocal aspects of these patients, taking into account variables, such as age, body mass index, use of bronchodilators, presence of symptoms, and quality of life related to voice. METHODS: Complete records of 25 subjects with chronic obstructive pulmonary disease, both sexes, aged 31 to 85 years, evaluated by forced vital capacity, maximum phonation times of /a/, and numerical count and number reached at this count, Vocal Symptom Scale, Voice Quality of Life. Data were presented descriptively and statistically analyzed using Student's t test for independent samples and Mann-Whitney U test. A significance level of 5% was accepted. The receiver operating characteristic curve was plotted and the standardized value of forced vital capacity <80% was considered as an indicator of pulmonary dysfunction. RESULTS: Patients exhibited reduced maximum phonation times for /a/, numeric counting, and reached digits in counting; discrepancies in Vocal Signs and Symptoms and Voice Quality of Life Scale scores. Numeric counting times of up to 12.5 seconds indicated that forced vital capacity may be impaired. CONCLUSION: The patients with chronic obstructive pulmonary disease examined in this study exhibited vocal deviations as evidenced by reduced maximum phonation times of /a/, numeric counting, and the digit reached during counting, as well as deviations in vocal self-assessment. Maximum phonation time in numerical counting was considered a biomarker of pulmonary function impairment.

Multiple behavioral risk factors for non-communicable diseases among the adolescent population in Brazil: the analysis derived from the Brazilian national survey of school health 2019.

BACKGROUND: Health risk behaviors often emerge or intensify during adolescence and tend to co-occur, exposing individuals to an even greater risk for the development of non-communicable diseases (NCDs). The likelihood of exhibiting multiple health risk factors also increases throughout life and is associated with sociodemographic characteristics contributing to their escalation and severity. In this context, the objective of this study was to analyze the association between sociodemographic characteristics and multiple behavioral risk factors for non-communicable diseases among the adolescent population in Brazil. METHODS: This cross-sectional study utilized data from the Brazilian National Survey of School Health 2019. The sample comprised 121,580 adolescents aged 13 to 17. The analyzed variables included irregular intake of fruits and vegetables, regular consumption of soft drinks and treats, insufficient physical activity, sedentary lifestyle, cigarette smoking, and alcohol consumption. To analyze MBRFs, a classification ranging from zero to five was created, and associations were estimated using Odds Ratio (OR) with the respective 95% confidence interval (CI). The Backward method was employed for the multivariate regression model, utilizing ordinal logistic regression. RESULTS: Adolescents without behavioral risk factors for NCDs constituted only 3.9% (95% CI 3.7-4.1). The most prevalent categories were two and three MBRFs, accounting for 28.3% (95% CI: 27.7-28.8) and 27.0% (95% CI: 26.5-27.5), respectively. Adolescents aged 16 and 17 (ORadj: 1.39; 95% CI: 1.32-1.48), residing in the Brazilian Southeast (ORadj: 1.66; 95% CI: 1.52-1.81), and those reporting poor or very poor self-rated health (ORadj: 2.05; 95% CI: 1.87-2.25) were more likely to exhibit multiple behavioral risk factors. Conversely, male adolescents (adjusted OR: 0.65; 95% CI: 0.62-0.69), those of mixed race (adjusted OR: 0.92; 95% CI: 0.87-0.97), and residents of rural areas (adjusted OR: 0.76; 95% CI: 0.70-0.84) were less likely to manifest MBRFs for NCDs. CONCLUSION: The majority of adolescents displayed MBRFs for NCDs, positively associated with age, region, and perceived health status. This underscores the necessity for healthcare promotional interventions throughout the life cycle, as these behaviors may persist into adulthood.

Home-Use Transcranial Direct Current Stimulation for the Treatment of a Major Depressive Episode: A Randomized Clinical Trial.

Importance: Transcranial direct current stimulation (tDCS) is moderately effective for depression when applied by trained staff. It is not known whether self-applied tDCS, combined or not with a digital psychological intervention, is also effective. Objective: To determine whether fully unsupervised home-use tDCS, combined with a digital psychological intervention or digital placebo, is effective for a major depressive episode. Design, Setting, and Participants: This was a double-blinded, sham-controlled, randomized clinical trial with 3 arms: (1) home-use tDCS plus a digital psychological intervention (double active); (2) home-use tDCS plus digital placebo (tDCS only), and (3) sham home-use tDCS plus digital placebo (double sham). The study was conducted between April 2021 and October 2022 at participants' homes and at Instituto de Psiquiatria do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, Brazil. Included participants were aged 18 to 59 years with major depression and a Hamilton Depression Rating Scale, 17-item version (HDRS-17), score above 16, a minimum of 8 years of education, and access to a smartphone and internet at home. Exclusion criteria were other psychiatric disorders, except for anxiety; neurologic or clinical disorders; and tDCS contraindications. Interventions: tDCS was administered in 2-mA, 30-minute prefrontal sessions for 15 consecutive weekdays (1-mA, 90-second duration for sham) and twice-weekly sessions for 3 weeks. The digital intervention consisted of 46 sessions based on behavioral therapy. Digital placebo was internet browsing. Main Outcomes and Measures: Change in HDRS-17 score at week 6. Results: Of 837 volunteers screened, 210 participants were enrolled (180 [86%] female; mean [SD] age, 38.9 [9.3] years) and allocated to double active (n = 64), tDCS only (n = 73), or double sham (n = 73). Of the 210 participants enrolled, 199 finished the trial. Linear mixed-effects models did not reveal statistically significant group differences in treatment by time interactions for HDRS-17 scores, and the estimated effect sizes between groups were as follows: double active vs tDCS only (Cohen d, 0.05; 95% CI, -0.48 to 0.58; P = .86), double active vs double sham (Cohen d, -0.20; 95% CI, -0.73 to 0.34; P = .47), and tDCS only vs double sham (Cohen d, -0.25; 95% CI, -0.76 to 0.27; P = .35). Skin redness and heat or burning sensations were more frequent in the double active and tDCS only groups. One nonfatal suicide attempt occurred in the tDCS only group. Conclusions and Relevance: Unsupervised home-use tDCS combined with a digital psychological intervention or digital placebo was not found to be superior to sham for treatment of a major depressive episode in this trial. Trial Registration: ClinicalTrials.gov Identifier: NCT04889976.

Discovery of new piperaquine hybrid analogs linked by triazolopyrimidine and pyrazolopyrimidine scaffolds with antiplasmodial and transmission blocking activities.

The World Health Organization (WHO) estimated that there were 247 million malaria cases in 2021 worldwide, representing an increase in 2 million cases compared to 2020. The urgent need for the development of new antimalarials is underscored by specific criteria, including the requirement of new modes of action that avoid cross-drug resistance, the ability to provide single-dose cures, and efficacy against both assexual and sexual blood stages. Motivated by the promising results obtained from our research group with [1,2,4]triazolo[1,5-a]pyrimidine and pyrazolo[1,5-a]pyrimidine derivatives, we selected these molecular scaffolds as the foundation for designing two new series of piperaquine analogs as potential antimalarial candidates. The initial series of hybrids was designed by substituting one quinolinic ring of piperaquine with the 1,2,4-triazolo[1,5-a]pyrimidine or pyrazolo[1,5-a]pyrimidine nucleus. To connect the heterocyclic systems, spacers with 3, 4, or 7 methylene carbons were introduced at the 4 position of the quinoline. In the second series, we used piperazine as a spacer to link the 1,2,4-triazolo[1,5-a]pyrimidine or pyrazolo[1,5-a]pyrimidine group to the quinoline core, effectively merging both pharmacophoric groups via a rigid spacer. Our research efforts yielded promising compounds characterized by low cytotoxicity and selectivity indices exceeding 1570. These compounds displayed potent in vitro inhibitory activity in the low nanomolar range against the erythrocytic form of the parasite, encompassing both susceptible and resistant strains. Notably, these compounds did not show cross-resistance with either chloroquine or established P. falciparum inhibitors. Even though they share a pyrazolo- or triazolo-pyrimidine core, enzymatic inhibition assays revealed that these compounds had minimal inhibitory effects on PfDHODH, indicating a distinct mode of action unrelated to targeting this enzyme. We further assessed the compounds' potential to interfere with gametocyte and ookinete infectivity using mature P. falciparum gametocytes cultured in vitro. Four compounds demonstrated significant gametocyte inhibition ranging from 58 % to 86 %, suggesting potential transmission blocking activity. Finally, we evaluated the druggability of these new compounds using in silico methods, and the results indicated that these analogs had favorable physicochemical and ADME (absorption, distribution, metabolism, and excretion) properties. In summary, our research has successfully identified and characterized new piperaquine analogs based on [1,2,4]triazolo[1,5-a]pyrimidine and pyrazolo[1,5-a]pyrimidine scaffolds and has demonstrated their potential as promising candidates for the development of antimalarial drugs with distinct mechanisms of action, considerable selectivity, and P. falciparum transmission blocking activity.

Dental pain report in children and genetic polymorphism (rs4818) in Catechol-O-Methyltransferase (COMT) gene: a cross- sectional study.

AIM: Polymorphisms in the COMT gene can alter enzymatic functions, raising levels of endogenous catecholamines, which stimulates beta-adrenergic receptors related to pain. This study aimed to evaluate whether a polymorphism in the COMT gene (rs4818) is associated with dental pain in children. METHODOLOGY: A cross-sectional study was conducted with a representative sample of 731 pairs of children and parents randomly selected from a population-based sample of eight-year-old children. Reports of dental pain was evaluated using a question directed at the parents and self-reported pain using the Faces Pain Scale - Revised. Dental caries experience was determined using the Decayed, Missing, and Filled Teeth (DMFT) index. For genetic analysis, DNA was obtained from oral mucosa epithelial cells of 352 children randomly selected from the initial sample. RESULTS: Children with the CC genotype had higher odds of reporting moderate to intense pain than those with the GG genotype (OR=3.60; 95% CI=0.80-16.20; p=0.03). These same children had greater odds of parental reports of pain (OR=1.93; 95% CI=0.91-4.08; p=0.02). Moreover, lower schooling of parents/guardians and caries experience in the primary dentition were significantly associated with greater odds of a parental report of dental pain (OR=2.06; 95% CI=1.47-2.91; p<0.001; OR=6.26; 95% CI=4.46-8.78; p<0.001). CONCLUSIONS: The rs4818 polymorphism of the COMT gene is associated with dental pain. Children with the C allele are more likely to report higher levels of pain. Clinical Relevance: Even though the experience of pain is subjective and multifactorial, this study raises the hypothesis that there is a genetic predisposition to dental pain that should be considered in clinical practice.

Biochemical Markers for Liver Injury in Zebrafish Larvae.

Liver plays a crucial role in detoxification processes and metabolism of xenobiotics, and therefore, it is a target organ of toxicity of different classes of chemicals. In this context, some key enzymes present in liver are considered to be good biochemical markers of hepatic damage and can have their activities determined via spectrophotometry. Aspartate and alanine aminotransferases, alkaline phosphatase, lactate dehydrogenase, and glutathione peroxidase are enzymes that have activities often changed in response to hepatotoxic compounds and can be accessed through the larval period of zebrafish (Danio rerio). In this chapter, we described methodologies for analyses of these five biomarkers in pooled zebrafish larvae through spectrophotometry.

Predictors of Post-COVID-19 Functional Status Scale in Hospitalized Patients Recovering From SARS-CoV-2 Infection.

OBJECTIVE: The study aimed to investigate whether peripheral and inspiratory muscle strength and architecture, functional capacity, functional mobility, fatigue, and health-related quality of life are predictors of the Post-COVID-19 Functional Status Scale score in patients with post-COVID-19 syndrome who were hospitalized. DESIGN: A cross-sectional study included 69 patients (53.3 ± 13.2 yrs, 36 men) with post-COVID-19 syndrome. The following outcomes were assessed: peripheral (dynamometry) and inspiratory (manovacuometry) muscle strength, muscle architecture (ultrasound), functional capacity (six-minute walk test), functional mobility (Timed Up and Go), fatigue (Functional Assessment of Chronic Illness Therapy), health-related quality of life (36-item Short-Form Health Survey), and functional status (Post-COVID-19 Functional Status scale). RESULTS: Functional mobility (ß = 0.573, P < 0.001), vastus intermedius echogenicity (ß = -0.491, P = 0.001), length of stay (ß = 0.349, P = 0.007), and female sex (ß = 0.415, P = 0.003) influenced the Post-COVID-19 Functional Status Scale. CONCLUSIONS: Functional mobility, muscle quality of the vastus intermedius, length of stay, and female sex influence the Post-COVID-19 Functional Status Scale score in this population. It is noteworthy that functional mobility is an independent predictor of Post-COVID-19 Functional Status Scale.