High-intensity interval training alleviates liver inflammation by regulating the TLR4/NF-κB signaling pathway and M1/M2 macrophage balance in female rats with cisplatin hepatotoxicity.

Cisplatin (CDDP) is an antineoplastic drug whose adverse effects include hepatotoxicity. The inflammatory process is crucial in the progression of liver injuries. Exercise is known for its anti-inflammatory effects, but the influence of different training modalities on hepatoprotection is still unclear. This study aims to compare the impacts between preconditioning with high-intensity interval training (HIIT) and traditional continuous training of low (LT) and moderate (MT) intensities on inflammatory markers in Wistar female rats with CDDP-induced hepatotoxicity. Thirty-five rats were divided into five groups: control and sedentary (C + Sed), treated with CDDP and sedentary (CDDP + Sed), treated with CDDP and subjected to LT (CDDP + LT), treated with CDDP and subjected to MT (CDDP + MT), and treated with CDDP and subjected to HIIT (CDDP + HIIT). The training protocols consisted of treadmill running for 8 weeks before CDDP treatment. The rats were euthanized 7 days after the treatment. Liver samples were collected to evaluate the expression of various inflammatory markers and types of macrophages. Our results indicated that HIIT was the only protocol to prevent the increase in all analyzed pro-inflammatory cytokines and reduce the number of ED-1-positive cells, attenuating the TLR4/NF-κB signaling pathway in the liver. Additionally, HIIT increased the anti-inflammatory cytokine IL-10 and regulated M1/M2 macrophage polarization. Thus, this study suggests that preconditioning with HIIT is more effective in promoting hepatoprotective effects than LT and MT, regulating inflammatory markers through modulation of the TLR4/NF-κB signaling pathway and M2 macrophage polarization in the hepatic tissue of female rats treated with CDDP.

Genetic architecture of congenital hypogonadotropic hypogonadism: insights from analysis of a Portuguese cohort.

STUDY QUESTION: What is the contribution of genetic defects in Portuguese patients with congenital hypogonadotropic hypogonadism (CHH)? SUMMARY ANSWER: Approximately one-third of patients with CHH were found to have a genetic cause for their disorder, with causal pathogenic and likely pathogenic germline variants distributed among 10 different genes; cases of oligogenic inheritance were also included. WHAT IS KNOWN ALREADY: CHH is a rare and genetically heterogeneous disorder characterized by deficient production, secretion, or action of GnRH, LH, and FSH, resulting in delayed or absent puberty, and infertility. STUDY DESIGN SIZE DURATION: Genetic screening was performed on a cohort of 81 Portuguese patients with CHH (36 with Kallmann syndrome and 45 with normosmic hypogonadotropic hypogonadism) and 263 unaffected controls. PARTICIPANTS/MATERIALS SETTING METHODS: The genetic analysis was performed by whole-exome sequencing followed by the analysis of a virtual panel of 169 CHH-associated genes. The main outcome measures were non-synonymous rare sequence variants (population allele frequency <0.01) classified as pathogenic, likely pathogenic, and variants of uncertain significance (VUS). MAIN RESULTS AND THE ROLE OF CHANCE: A genetic cause was identified in 29.6% of patients. Causal pathogenic and likely pathogenic variants were distributed among 10 of the analysed genes. The most frequently implicated genes were GNRHR, FGFR1, ANOS1, and CHD7. Oligogenicity for pathogenic and likely pathogenic variants was observed in 6.2% of patients. VUS and oligogenicity for VUS variants were observed in 85.2% and 54.3% of patients, respectively, but were not significantly different from that observed in controls. LARGE SCALE DATA: N/A. LIMITATIONS REASONS FOR CAUTION: The identification of a large number of VUS presents challenges in interpretation and these may require reclassification as more evidence becomes available. Non-coding and copy number variants were not studied. Functional studies of the variants were not undertaken. WIDER IMPLICATIONS OF THE FINDINGS: This study highlights the genetic heterogeneity of CHH and identified several novel variants that expand the mutational spectrum of the disorder. A significant proportion of patients remained without a genetic diagnosis, suggesting the involvement of additional genetic, epigenetic, or environmental factors. The high frequency of VUS underscores the importance of cautious variant interpretation. These findings contribute to the understanding of the genetic architecture of CHH and emphasize the need for further studies to elucidate the underlying mechanisms and identify additional causes of CHH. STUDY FUNDING/COMPETING INTERESTS: This research was funded by the Portuguese Foundation for Science and Technology (grant numbers PTDC/SAU-GMG/098419/2008, UIDB/00709/2020, CEECINST/00016/2021/CP2828/CT0002, and 2020.04924.BD) and by Sidra Medicine-a member of the Qatar Foundation (grant number SDR400038). The authors declare no competing interests.

Effects of cocoa consumption on cardiometabolic risk markers: Protocol for a systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Cardiometabolic diseases cover a spectrum of interrelated conditions linked to metabolic dysfunctions and/or cardiovascular disorders, including systemic arterial hypertension, diabetes mellitus, dyslipidemia, and obesity. Cocoa is a rich source of dietary polyphenols and has been associated with cardiovascular health benefits. However, beneficial effects of cocoa consumption and appropriate quantities in decreasing cardiometabolic risk factors have yet to be established. Therefore, we will conduct a systematic review and meta-analysis to examine the effects of cocoa consumption on cardiometabolic risk markers (total cholesterol, HDL, LDL, triglycerides, blood glucose, glycated hemoglobin, waist circumference, abdominal circumference, body mass index, systolic blood pressure and diastolic blood pressure) in adults with or without established cardiovascular risk factors. METHODS: Our review will include all randomized controlled trials published in English, Portuguese and Spanish with no date of publication restrictions evaluating the effects of cocoa consumption on cardiometabolic risk markers selected from the databases MEDLINE (PubMed), LILACS, Cochrane, EMBASE, Web of Science and SciELO, and gray literature. Eligible studies must involve adults (age ≥18y), and the consumption of cocoa or dark chocolate (≥ 70% cocoa), include a control group and evaluate blood pressure, anthropometric measurements, and lipid or glycemic profiles. We will use risk-of-bias 2 (RoB2) tool to assess the risk of bias and the GRADE system to assess the strength of evidence. Statistical analyses will be performed using RStudio for Windows and R package meta. DISCUSSION: This meta-analysis will summarize existing evidence on the effects of cocoa consumption on cardiometabolic health in adults. Better understanding the effects of cocoa consumption on anthropometric measurements, blood pressure, and lipid and glycemic profiles can provide valuable insights for health professionals to improve dietary recommendations regarding appropriate quantities. TRIAL REGISTRATION: Systematic Review Registration: PROSPERO CRD42023484490.

Children and adolescents assisted in a referral oral medicine diagnostic service: 20 years of experience in Brazil.

BACKGROUND: Several lesions can affect the oral and maxillofacial region, with trends influenced by lifestyle and age. AIM: To investigate the occurrence of oral and maxillofacial lesions in paediatric patients assisted in an oral medicine diagnostic service in Brazil over 20 years. DESIGN: A retrospective cross-sectional study was performed in an oral medicine diagnostic service (1999-2019). Data included sex, age, anatomic site, and diagnosis from clinical records of children (0-9 years) and adolescents (10-19 years). Lesions were diagnosed through clinical examination. Biopsy and histopathologic examination were performed when necessary. RESULTS: Among 10 530 records, 702 (6.67%) were from patients aged 0-19 years diagnosed with oral or maxillofacial lesions. A high frequency of females was observed (58.1%). Reactive/inflammatory lesions were the most common group of lesions (45.2%), followed by abnormalities of teeth/developmental defects (17.8%) and pulpal and periapical diseases (8.5%). Mucocele/ranula was the most common lesion in children (29.3%) and adolescents (25.3%). Lips were the most affected anatomic sites. CONCLUSION: Most lesions were benign, and mucocele/ranula was the most frequent. Our results did not differ from those of histopathological-based studies, but they provided information on the occurrence of oral and maxillofacial lesions to dentists and paediatricians.

Obstetric racism, a debate under construction in Brazil: perceptions of black women on obstetric violence. / Racismo obstétrico, um debate em construção no Brasil: percepções de mulheres negras sobre a violência obstétrica.

This article aims to know the perception of women on obstetric violence from a racial perspective. This was a qualitative study carried out in a public maternity hospital with 25 women in the city of Salvador, Bahia, Brazil. Data were collected through semi-structured interviews and participant observation from November 2021 to February 2022. Content analysis was used to organize the data obtained through the interviews. The results were analyzed through the theoretical contributions of intersectionality, focusing on the interaction between obstetric violence and obstetric racism. The narratives discuss issues of obstetric violence, institutional racism, and how these experiences are permeated by issues of race, gender, and class. Questions related to the feelings of these women regarding the experience of violence at the time of childbirth care were also highlighted. Obstetric racism denies reproductive rights and hinders access to respectful and equitable care for black women.

O objetivo deste artigo é conhecer a percepção de mulheres sobre a violência obstétrica em uma perspectiva racial. Trata-se de uma pesquisa qualitativa realizada em uma maternidade pública, com 25 mulheres, no município de Salvador, Bahia, Brasil. Os dados foram coletados por meio de entrevistas semiestruturadas e observação participante, no período de novembro de 2021 a fevereiro de 2022. Utilizou-se, para organização dos dados obtidos através das entrevistas, a análise de conteúdo. Os resultados foram analisados através das contribuições teóricas da interseccionalidade, tendo como foco a interação entre violência obstétrica e racismo obstétrico. As narrativas discorrem sobre questões da violência obstétrica, racismo institucional, e como essas vivências são permeadas pelas questões de raça, gênero e classe. Foram apontadas também questões relacionadas aos sentimentos dessas mulheres frente a vivência da violência no momento da assistência ao parto. O racismo obstétrico nega os direitos reprodutivos e dificulta o acesso a uma assistência respeitosa e equânime as mulheres negras.

Explicit discrimination among Brazilian dental students: A multicenter study.

OBJECTIVE: To test the association between socioeconomic and sociodemographic status of Brazilian dental students with discriminatory experiences suffered by them. METHODS: This multicenter cross-sectional study was conducted with 531 undergraduate dental students from four different Brazilian states. The Explicit Discrimination Scale (EDS) was used to measure the experience of discrimination in several daily situations. A questionnaire about sociodemographic and socioeconomic characteristics, form of admission, and permanence in dental schools was developed and validated by experts and six dental students through cognitive interviews. The EDS and questionnaire were sent to students by an online platform using snowball sampling. Descriptive analysis, bivariate tests, and multiple Poisson regression were performed. RESULTS: Among the participants, most were female, white, heterosexual, and cisgender. The mean EDS total score was higher among those students who used Brazilian Affirmative Actions for higher education access and permanence (p < 0.005). The multiple analysis indicated that students who were black (prevalence ratio [PR] = 1.484; 95% confidence interval [95%CI]: 1.291-1.705), women (PR = 1.227; 95%CI: 1.030-1.462), had lower monthly income (PR = 1.212; 95%CI: 1.043-1.409) and were lesbian, gay, bisexual, transgender, intersex, queer, pansexual, and plus (LGBTQIAP+) (PR = 1.466; 95%CI: 1.238-1.735) showed a higher probability of discriminatory experiences when compared to white, male and heterosexual students with higher monthly income. CONCLUSION: There is a racial and social class pattern among dental students. The exclusionary factors such as black race, female gender, lower monthly income and being LGBTQIAP+ make students more vulnerable to discriminatory experiences.

Fibroblasts Promote Resistance to KRAS Silencing in Colorectal Cancer Cells.

Colorectal cancer (CRC) responses to KRAS-targeted inhibition have been limited due to low response rates, the mechanisms of which remain unknown. Herein, we explored the cancer-associated fibroblasts (CAFs) secretome as a mediator of resistance to KRAS silencing. CRC cell lines HCT15, HCT116, and SW480 were cultured either in recommended media or in conditioned media from a normal colon fibroblast cell line (CCD-18Co) activated with rhTGF-ß1 to induce a CAF-like phenotype. The expression of membrane stem cell markers was analyzed by flow cytometry. Stem cell potential was evaluated by a sphere formation assay. RNAseq was performed in KRAS-silenced HCT116 colonospheres treated with either control media or conditioned media from CAFs. Our results demonstrated that KRAS-silencing up-regulated CD24 and down-regulated CD49f and CD104 in the three cell lines, leading to a reduction in sphere-forming efficiency. However, CAF-secreted factors restored stem cell marker expression and increased stemness. RNA sequencing showed that CAF-secreted factors up-regulated genes associated with pro-tumorigenic pathways in KRAS-silenced cells, including KRAS, TGFß, NOTCH, WNT, MYC, cell cycle progression and exit from quiescence, epithelial-mesenchymal transition, and immune regulation. Overall, our results suggest that resistance to KRAS-targeted inhibition might derive not only from cell-intrinsic causes but also from external elements, such as fibroblast-secreted factors.

Pemphigus vulgaris and mucous membrane pemphigoid: A systematic review of clinical manifestations, diagnosis, and treatment.

Pemphigus vulgaris (PV) and mucous membrane pemphigoid (MMP) are mucocutaneous autoimmune diseases characterized by blistering lesions of mucous membranes and skin, with very similar clinical manifestations. This study aimed to systematically review the literature on the clinical and demographic profile, diagnostic methods, and treatment of patients with pemphigus vulgaris (PV) and mucous membrane pemphigoid (MMP). Studies describing cases of PV and MMP diagnosed by direct immunofluorescence that exhibited intraoral manifestations were included. Thirty-two articles were included, with 18 studies on PV and 15 on MMP, corresponding to 50 and 123 cases diagnosed as PV and MMP, respectively. Most patients with PV (64 %) and MMP (81.3 %) were women in the fifth and sixth decade of life, respectively. The mouth was the primary site of involvement both in PV (71.4 %) and in MMP (91 %). The cheek mucosa and gingiva were the most frequently affected intraoral sites in PV (30 %) and MMP (64.2 %), respectively. Direct immunofluorescence was positive for IgG in all cases of the two conditions. The treatment of choice was systemic corticosteroid therapy for patients with PV (50 %) and topical treatment for patients with MMP (53.7 %). Differences in intraoral site predilection, extraoral involvement, and the results of diagnostic tests allow us to trace the clinical, demographic, and diagnostic profile of PV and MMP that contributes to differential diagnosis and therapeutic management.

[Calculation of the alcohol per capita consumption in Brazil: using national dataCálculo del indicador del consumo de alcohol per cápita en Brasil: uso de datos nacionales]. / Cálculo do indicador de consumo de álcool per capita no Brasil: uso de dados nacionais.

Objective: To calculate the alcohol per capita consumption (APC) in Brazil (Brazil APC) using national data and to establish the Brazil APC as gold standard for the country, replacing the indicator previously calculated by the World Health Organization (WHO) based on international data. Method: The Brazilian public data sources necessary for calculating the recorded APC were selected, and the alcohol concentration was defined by beverage category. For the variables of tourist APC and unrecorded APC, which are unavailable in Brazil, estimates from the United Nations (UN) and the WHO were used. The Brazil APC indicator was calculated and compared to the indicator produced by the WHO through analysis of the medians obtained for the period from 2005 to 2020. Results: The national alcohol consumption indicator was 9.2 liters per capita in 2005, reaching 9.8 in 2020. The WHO indicator showed a consumption of 8.4 liters per capita in 2005, decreasing until 2016 and slightly increasing to 7.8 in 2020. Conclusion: The Brazil APC was calculated based on national sources and showed a distinct trend compared to the WHO indicator, which showed a decrease. The regular and transparent provision of this indicator through government channels will support the development of policies to address alcohol consumption in the country.

Objetivo: Calcular el indicador del consumo de alcohol per cápita en Brasil a partir de datos nacionales, con miras a establecerlo como patrón de referencia para el país en sustitución del indicador calculado anteriormente por la Organización Mundial de la Salud a partir de datos internacionales. Métodos: Se seleccionaron las fuentes públicas de datos de Brasil necesarias para estructurar el cálculo del consumo de alcohol per cápita registrado y se definió la concentración de alcohol por clase de bebida. Para las variables de consumo de alcohol per cápita por parte de turistas y consumo per cápita no registrado, que no están disponibles en Brasil, se utilizaron estimaciones de las Naciones Unidas y de la Organización Mundial de la Salud. Se calculó el indicador del consumo de alcohol per cápita en Brasil y se comparó con el indicador elaborado por la OMS mediante un análisis de las medianas correspondientes al período 2005-2020. Resultados: El indicador nacional del consumo de alcohol fue de 9,2 litros per cápita en el 2005, con un aumento a 9,8 en el 2020. El indicador de la Organización Mundial de la Salud mostró un consumo de 8,4 litros per cápita en el 2005, con una reducción hasta el 2016 y un leve aumento a 7,8 en el 2020. Conclusión: Se calculó el consumo de alcohol per cápita en Brasil a partir de fuentes nacionales, lo que mostró una tendencia distinta de la tendencia descendente del indicador de la Organización Mundial de la Salud. La disponibilidad transparente y regular de este indicador por medio de los canales gubernamentales permitirá su seguimiento, con lo cual se podrán formular políticas para enfrentar el consumo de alcohol en el país.

Effects of Cocoa Consumption on Cardiometabolic Risk Markers: Meta-Analysis of Randomized Controlled Trials.

BACKGROUND: We conducted a systematic review and meta-analysis to examine the effect of dietary intake of cocoa on anthropometric measurements, lipid and glycemic profiles, and blood pressure levels in adults, with and without comorbidities. METHODS: The databases used were MEDLINE (PubMed), EMBASE, Web of Science, Cochrane, LILACS, and SciELO. The eligible studies were randomized clinical trials (RCTs) involving adults undergoing cocoa consumption (cocoa extract or ≥70% cocoa dark chocolate) for ≥4 weeks that evaluated at least one of the following markers: body weight, body mass index (BMI), waist/abdominal circumference, total cholesterol, LDL-c, triglycerides, HDL-c, blood glucose, glycated hemoglobin (HbA1c), and systolic and diastolic blood pressure (SBP/DBP). RESULTS: Thirty-one studies were included, totaling 1986 participants. Cocoa consumption showed no effects on body weight, BMI, waist circumference, triglycerides, HDL-c and HbA1c. Yet, there was a reduction in total cholesterol (-8.35 mg/dL, 95% CI -14.01; -2.69 mg/dL), LDL-c (-9.47 mg/dL, 95% CI -13.75; -5.20 mg/dL), fasting blood glucose (-4.91 mg/dL, 95% CI -8.29; -1.52 mg/dL), SBP (-2.52 mmHg, 95% CI -4.17; -0.88 mmHg), and DBP (-1.58 mmHg, 95% CI -2.54; -0.62 mmHg). CONCLUSIONS: The consumption of cocoa showed protective effects on major cardiometabolic risk markers that have a clinical impact in terms of cardiovascular risk reduction.

Forensic study of the mechanical properties of prosthetic materials: Submersion in mangrove environment - A pilot study.

INTRODUCTION: It is crucial for dental surgeons to use the mechanical properties of dental prosthetic materials to correlate the submersion time in a mangrove environment. OBJECTIVE: This study aimed to submerge dental prosthetic materials, such as acrylic resin and zirconia, contained within acrylic resin disks in a mangrove environment, and analyze the alterations in mechanical parameters, such as surface roughness and microhardness, to estimate submergence time in similar forensic situations. MATERIALS AND METHODS: A total of 6 specimens was embedded in acrylic resin disks numbered from 1 to 6. The materials were polished for initial parameter readings a day before submersion, and new readings were obtained 1after submersion. All specimens were subjected to surface roughness analysis, in addition to Knoop microhardness analysis for acrylic resin and Vickers microhardness analysis for zirconia. After the experiment, the data were computed for statistical comparation of the materials properties different parameters. RESULTS: There was a significant increase in surface roughness and Knoop microhardness was reduced in the Acrylic Resin samples (p< 0.05); however, no statistically significant differences were observed in the roughness or Vickers microhardness values of the zirconia samples. CONCLUSION: Zirconia prosthetics were more resistant to degradation when submerged in a mangrove environment compared to acrylic resin ones; however, owing to the obstacles inherent in this study, we suggest further research on the properties of prosthetic materials submerged in mangroves or other environments, which could bolster the work of dental professionals in forensic medical institutes.

Abnormal neurovascular control during central and peripheral chemoreceptors stimulation in heart failure patients with preserved ejection fraction.

PURPOSE: Central and peripheral chemoreceptors are hypersensitized in patients with heart failure with reduced ejection fraction. Whether this autonomic alteration occurs in patients with heart failure with preserved ejection fraction (HFpEF) remains little known. We test the hypothesis that the central and peripheral chemoreflex control of muscle sympathetic nerve activity (MSNA) is altered in HFpEF. METHODS: Patients aged 55-80 years with symptoms of heart failure, body mass index ≤ 35 kg/m2, left ventricular ejection fraction > 50%, left atrial volume index > 34 mL/m2, left ventricular early diastolic filling velocity and early diastolic tissue velocity of mitral annulus ratio (E/e' index) ≥ 13, and BNP levels > 35 pg/mL were included in the study (HFpEF, n = 9). Patients without heart failure with preserved ejection fraction (non-HFpEF, n = 9), aged-paired, were also included in the study. Peripheral chemoreceptors stimulation (10% O2 and 90% N2, with CO2 titrated) and central chemoreceptors stimulation (7% CO2 and 93% O2) were conducted for 3 min. MSNA was evaluated by microneurography technique, and forearm blood flow (FBF) by venous occlusion plethysmography. RESULTS: During hypoxia, MSNA responses were greater (p < 0.001) and FBF responses were lower in patients with HFpEF (p = 0.006). Likewise, MSNA responses during hypercapnia were higher (p < 0.001) and forearm vascular conductance (FVC) levels were lower (p = 0.030) in patients with HFpEF. CONCLUSIONS: Peripheral and central chemoreflex controls of MSNA are hypersensitized in patients with HFpEF, which seems to contribute to the increase in MSNA in these patients. In addition, peripheral and central chemoreceptors stimulation in patients with HFpEF causes muscle vasoconstriction.

SAnDReS 2.0: Development of machine-learning models to explore the scoring function space.

Classical scoring functions may exhibit low accuracy in determining ligand binding affinity for proteins. The availability of both protein-ligand structures and affinity data make it possible to develop machine-learning models focused on specific protein systems with superior predictive performance. Here, we report a new methodology named SAnDReS that combines AutoDock Vina 1.2 with 54 regression methods available in Scikit-Learn to calculate binding affinity based on protein-ligand structures. This approach allows exploration of the scoring function space. SAnDReS generates machine-learning models based on crystal, docked, and AlphaFold-generated structures. As a proof of concept, we examine the performance of SAnDReS-generated models in three case studies. For all three cases, our models outperformed classical scoring functions. Also, SAnDReS-generated models showed predictive performance close to or better than other machine-learning models such as KDEEP, CSM-lig, and ΔVinaRF20. SAnDReS 2.0 is available to download at https://github.com/azevedolab/sandres.

Predictors of unsuccessful tuberculosis treatment outcomes in Brazil: an analysis of 259,484 patient records.

INTRODUCTION: Tuberculosis (TB) causes over 1 million deaths annually. Providing effective treatment is a key strategy for reducing TB deaths. In this study, we identified factors associated with unsuccessful treatment outcomes among individuals treated for TB in Brazil. METHODS: We obtained data on individuals treated for TB between 2015 and 2018 from Brazil's National Disease Notification System (SINAN). We excluded patients with a history of prior TB disease or with diagnosed TB drug resistance. We extracted information on patient-level factors potentially associated with unsuccessful treatment, including demographic and social factors, comorbid health conditions, health-related behaviors, health system level at which care was provided, use of directly observed therapy (DOT), and clinical examination results. We categorized treatment outcomes as successful (cure, completed) or unsuccessful (death, regimen failure, loss to follow-up). We fit multivariate logistic regression models to identify factors associated with unsuccessful treatment. RESULTS: Among 259,484 individuals treated for drug susceptible TB, 19.7% experienced an unsuccessful treatment outcome (death during treatment 7.8%, regimen failure 0.1%, loss to follow-up 11.9%). The odds of unsuccessful treatment were higher with older age (adjusted odds ratio (aOR) 2.90 [95% confidence interval: 2.62-3.21] for 85-100-year-olds vs. 25-34-year-olds), male sex (aOR 1.28 [1.25-1.32], vs. female sex), Black race (aOR 1.23 [1.19-1.28], vs. White race), no education (aOR 2.03 [1.91-2.17], vs. complete high school education), HIV infection (aOR 2.72 [2.63-2.81], vs. no HIV infection), illicit drug use (aOR 1.95 [1.88-2.01], vs. no illicit drug use), alcohol consumption (aOR 1.46 [1.41-1.50], vs. no alcohol consumption), smoking (aOR 1.20 [1.16-1.23], vs. non-smoking), homelessness (aOR 3.12 [2.95-3.31], vs. no homelessness), and immigrant status (aOR 1.27 [1.11-1.45], vs. non-immigrants). Treatment was more likely to be unsuccessful for individuals treated in tertiary care (aOR 2.20 [2.14-2.27], vs. primary care), and for patients not receiving DOT (aOR 2.35 [2.29-2.41], vs. receiving DOT). CONCLUSION: The risk of unsuccessful TB treatment varied systematically according to individual and service-related factors. Concentrating clinical attention on individuals with a high risk of poor treatment outcomes could improve the overall effectiveness of TB treatment in Brazil.

Clinical Characteristics of Genuine Acute Autoimmune Hepatitis.

Introduction: Autoimmune hepatitis (AIH) has a spectrum of symptoms ranging from asymptomatic disease to acute severe hepatitis, chronic hepatitis, and decompensated cirrhosis. The acute presentation is not rare and could represent genuine acute AIH (GAAIH) or acute exacerbation of chronic autoimmune hepatitis. We aimed to identify the prevalence, clinical features, and prognostic factors associated with GAAIH and compare these cases with acute exacerbation of chronic AIH. Methods: This cross-sectional observational study evaluated patients with acute AIH presentation, defined as total bilirubin >5 times the upper limit of normality (xULN) and/or alanine aminotransferase >10 xULN, and no prior history of liver disease. Histology findings of acute disease defined GAAIH. Bivariate analyses were performed to identify factors associated with the GAAIH, when compared with acute exacerbation of chronic AIH. Results: Seventy-two patients with acute presentation of AIH were included and six (8.3%) of them presented GAAIH. Comparative analysis between patients with GAAIH and patients with acute exacerbation of chronic AIH revealed that prothrombin activity (96% [74-100] vs. 61% [10-100]; p = 0.003) and albumin levels (3.9 ± 0.2 g/dL vs. 3.4 ± 0.5 g/dL; p < 0.001) were higher in patients with GAAIH. The International Autoimmune Hepatitis Group score was higher in patients with acute exacerbation of chronic AIH (18.5 [8-23] vs. 16.5 [15-17]; p = 0.010). Compared to 15.2% of acute exacerbation of chronic AIH, complete therapeutic response to treatment was achieved in 67.7% of cases with GAAIH (p = 0.018). Conclusions: GAAIH was rare (8.3%), and patients with this presentation exhibited more preserved liver function tests, suggesting that most cases presenting with loss of function are acute exacerbation of chronic AIH. Additionally, patients with GAAIH had a better complete therapeutic response, suggesting a more preserved liver function at presentation, and early diagnosis has a positive therapeutic implication.

Introdução: A hepatite autoimune (HAI) apresenta um espectro de sintomas que varia de doença assintomática a hepatite aguda grave, hepatite crónica e cirrose descompensada. A apresentação aguda não é rara e pode representar hepatite autoimune aguda genuína (HAIAG) ou exacerbação aguda de hepatite autoimune crónica (EAHAIC). O nosso objetivo foi identificar a prevalência, caraterísticas clínicas e fatores prognósticos associados à HAIAG, e comparar esses casos com EAHAIC. Métodos: Estudo observacional, transversal, incluindo doentes com apresentação aguda de HAI, definida como bilirrubina total > 5 vezes o limite superior da normalidade (xLSN) e/ou ALT > 10 xLSN, e sem história prévia de doença hepática. HAIAG foi definida pela presença de achados histológicos de doença aguda. Análises bivariadas foram realizadas para identificar fatores associados à HAIAG, quando comparado com o EAHAIC. Resultados: Foram incluídos setenta e dois doentes com apresentação aguda de HAI, dos quais seis (8.3%) com HAIAG. A análise comparativa entre doentes com HAIAG e doentes com EAHAIC mostrou que a atividade de protrombina (96% (74-100) versus 61% (10-100; p=0.003) e os níveis de albumina (3,9 ± 0,2 g/dL vs. 3,4 ± 0,5 g/dL; p < 0,001) foram significativamente mais elevados em pacientes com HAIAG. O score do Grupo Internacional de Hepatite Autoimune foi mais elevado em doentes com EAHAIC (18.5 (8-23) versus 16.5 (15-17); p=0.010). A resposta terapêutica completa ao tratamento foi alcançada em 66.7% dos casos de HAIAG (vs. 15,2% na EAHAIC, p=0,018). Conclusões: A HAIAG é rara (8.3%), e os doentes com esta apresentação mostraram testes de função hepática mais preservados, sugerindo que a maioria dos casos com perda de função são EAHAIC. Além disso, os doentes com HAIAG tiveram maior taxa de resposta terapêutica completa, sugerindo que uma função hepática mais preservada na apresentação e o diagnóstico precoce tem uma implicação terapêutica positiva.

An adapted cardioprotective diet with or without phytosterol and/or krill oil supplement in familial hypercholesterolemia: A pilot study protocol

BACKGROUND AND AIMS: A healthy diet is one of the pillars of familial hypercholesterolemia (FH) treatment. However, the best dietary pattern and indication for specific supplementation have not been established. Our aim is to conduct a pilot study to assess the effect of an adapted cardioprotective diet with or without phytosterol and/or krill oil supplement in participants with a probable or definitive diagnosis of FH, treated with moderate/high potency statins. METHODS: A national, multicenter, factorial, and parallel placebocontrolled randomized clinical trial with a superiority design and 1:1:1:1 allocation rate will be conducted. The participants will undergo whole exome sequencing and be allocated into four treatment groups: 1) a cardioprotective diet adapted for FH (DICAFH) þ phytosterol placebo þ krill oil placebo; 2) DICA-FH þ phytosterol 2 g/day þ krill oil placebo; 3) DICA-FH þ phytosterol placebo þ krill oil 2 g/day; or 4) DICA-FH þ phytosterol 2 g/day þ krill oil 2 g/day. The primary outcomes will be low-density lipoprotein (LDL)-cholesterol and lipoprotein (a) levels and adherence to treatment after a 120-day follow-up. LDL- and high-density lipoprotein (HDL)-cholesterol subclasses, untargeted lipidomics analysis, adverse events, and protocol implementation components will also be assessed. RESULTS: A total of 58 participants were enrolled between May e August 2023. After the end of the follow-up period, the efficacy and feasibility results of this pilot study will form the basis of the design of a large-scale randomized clinical trial. CONCLUSIONS: This study's overall goal is to recommend dietary treatment strategies in the context of FH.

Clinical and radiographic characteristics of pycnodysostosis: A systematic review.

Purpose: Pycnodysostosis (PYCD), an autosomal recessive syndrome, is characterized by an imbalance in bone remodeling that produces various clinical and radiographic craniofacial manifestations. This review represents a systematic examination of these manifestations, as well as oral features associated with PYCD. Materials and Methods: A systematic review was conducted across 8 databases from February to March 2023. The search strategy focused on studies reporting cases of PYCD that examined the clinical and radiographic craniofacial and oral characteristics associated with this syndrome. Results: The review included 84 studies, encompassing a total of 179 cases of PYCD. More than half of the patients were female (55.3%), and the mean age was 14.7 years. Parental consanguinity was reported in 51.4% of the cases. The most common craniofacial clinical manifestation was a prominent nose, observed in 57.5% of cases. Radiographically, the most frequently reported craniofacial characteristics included the presence of an obtuse mandibular angle (84.3%) and frontal cranial bosses (82.1%). Clinical and radiographic examinations revealed oral alterations, with micrognathia present in 62.6% of patients and malocclusion in 59.2%. Among dental anomalies, tooth agenesis was the most commonly reported, affecting 15.6% of patients. Conclusion: Understanding the clinical and radiographic craniofacial features of PYCD is crucial for dental professionals. This knowledge enables these clinicians to devise effective treatment plans and improve patient quality of life.

Is There Evidence of Crohn's Disease Exclusion Diet (CDED) in Remission of Active Disease in Children and Adults? A Systematic Review.

Crohn's disease (CD) is an inflammatory bowel disease. Previous research has explored the impact of diet on CD, as specific dietary components can influence gut microbiota and immune responses, contributing to damage in the gastrointestinal tract. The Crohn's Disease Exclusion Diet (CDED) is based on an exclusion diet; it is a recent dietary approach that is often used alongside partial enteral nutrition (PEN) and aims to induce disease remission by excluding certain dietary components. This study assesses the current evidence for the effectiveness of the CDED + PEN in achieving remission in both children and adults with active CD. Our systematic review followed PRISMA recommendations and was registered in PROSPERO with CRD number 42022335076. The searched databases were PubMed/MEDLINE, Cochrane Library, Scopus, and Web of Science. The included studies were analyzed using Rayyan software, and the risk of bias was assessed with Cochrane RevMan 5.0 software. The primary assessed outcome was clinical remission, evaluated with validated questionnaire scores such as PCDAI, CDAI, or HBI. All analyzed papers yielded promising results. Notably, the CDED + PEN demonstrated better tolerance than exclusive enteral nutrition (EEN), resulting in higher adherence rates. Therefore, the CDED + PEN appears to be a viable alternative for induction remission in active disease for both children and adults with CD.

Toxicity of Trixis vauthieri DC essential oil on Lutzomyia longipalpis (Diptera, Psychodidae, Phlebotominae), a proven vector of visceral leishmaniasis in Brazil.

BACKGROUND OBJECTIVES: In Brazil, one of the visceral leishmaniasis control measures in urban environments is the elimination of Lutzomyia longipalpis, which occurs through the application of pyrethroid insecticides with residual action in homes and outbuildings. Due to the loss of sensitivity of this vector to these insecticides, the search for more efficient insecticide compounds against L. longipalpis has been intensified. The objective of this work was to evaluate the toxicity of Trixis vauthieri essential oil on adult sandflies of the species L. longipalpis, and identify the phytochemical composition of these essential oils. METHODS: Essential oils from leaves collected from T. vauthieri at different times were obtained at concentrations of 5, 10 and 20 mg/mL. Twenty sandflies were exposed to the essential oils and the mortality was evaluated after 1, 2, 4, 16, 24, 48 and 72 h. The chemical constituents of the essential oil were also identified. RESULTS: The essential oils of T. vauthieri at a concentration of 20 mg/mL were the most toxic to sandflies, reaching a mortality rate of 98.33% and 95%, respectively, after 72 h of exposure. The analysis of chemical constituents revealed the presence of triterpenes and/or steroids, tannins, flavonoids, alkaloids, saponins and coumarins. INTERPRETATION CONCLUSION: The results obtained suggest that T. vauthieri essential oil is fairly promising as an insecticidal potential against L. longipalpis. A more detailed analysis of the oil's phytochemical composition is necessary to identify active and pure compounds that can be used in vector control of visceral leishmaniasis.