The usefulness of patient-reported outcome measures in decision making in Chagas cardiomyopathy: a scoping review.

Chagas cardiomyopathy (ChC) presents many biopsychosocial complexities, highlighting the need to have patient self-report questions. This study demonstrates the scope of the use of patient-reported outcome measures (PROMs) in patients with ChC and highlights the main research gaps. This is a scoping review and the search strategy was performed in the Online Medical Literature Analysis and Retrieval System (MEDLINE), Excerpta Medica database (EMBASE), Accumulated Index of Nursing and Allied Health Literature (CINAHL), Cochrane Central, Latin American Literature and Caribbean in Health Sciences (LILACS) and Diagnostic Test Accuracy (DITA). The search identified 4484 studies and 20 studies met the inclusion criteria. The Short-Form of 36 items (SF-36) had potential prognostic value and the ability to identify systolic dysfunction. The Human Activity Profile was able to screen for functional impairment, and the New York Heart Association showed potential prognostic value. The SF-36 and Minnesota Living with Heart Failure Questionnaire were responsive to interventions. The pharmaceutical care affected adherence to treatment as assessed by the Morisky score and also for SF-36. Despite the increased use of PROMs, there are still a large number of gaps in the literature, and further studies using PROMs are needed.

Circulating Blood Prognostic Biomarker Signatures for Hemorrhagic Cerebral Cavernous Malformations (CCMs).

Cerebral cavernous malformations (CCMs) are a neurological disorder characterized by enlarged intracranial capillaries in the brain, increasing the susceptibility to hemorrhagic strokes, a major cause of death and disability worldwide. The limited treatment options for CCMs underscore the importance of prognostic biomarkers to predict the likelihood of hemorrhagic events, aiding in treatment decisions and identifying potential pharmacological targets. This study aimed to identify blood biomarkers capable of diagnosing and predicting the risk of hemorrhage in CCM1 patients, establishing an initial set of circulating biomarker signatures. By analyzing proteomic profiles from both human and mouse CCM models and conducting pathway enrichment analyses, we compared groups to identify potential blood biomarkers with statistical significance. Specific candidate biomarkers primarily associated with metabolism and blood clotting pathways were identified. These biomarkers show promise as prognostic indicators for CCM1 deficiency and the risk of hemorrhagic stroke, strongly correlating with the likelihood of hemorrhagic cerebral cavernous malformations (CCMs). This lays the groundwork for further investigation into blood biomarkers to assess the risk of hemorrhagic CCMs.

Recurrent Chagas' disease meningomyelitis in an HIV-infected patient.

Chagas' disease reactivation leading to monophasic acute or subacute meningoencephalitis or space-occupying lesions is a well-described AIDS-defining condition in Latin America. We report a 59-year-old man native from the Northeast region of Brazil, with a second episode of subacute chagasic meningomyelitis. He had long-term multidrug-resistant HIV and had abandoned combined antiretroviral therapy (CD4+ lymphocyte count, 16 cells/mm³, and HIV viral load 169 403 copies/mL). He initially received benznidazole but switched to nifurtimox after developing myelotoxicity. He was discharged home having made a partial neurological improvement. Chagas' disease should be included in the differential diagnosis of meningomyelitis in people living with HIV/AIDS who are from endemic areas of this parasitic disease.

Big is not better: Comparing two alpha-Gal-bearing glycotopes in neoglycoproteins as biomarkers for Leishmania (Viannia) braziliensis infection.

The protozoan parasite Leishmania (Viannia) braziliensis is among Latin America's most widespread Leishmania species and is responsible for tegumentary leishmaniasis (TL). This disease has multiple clinical presentations, with cutaneous leishmaniasis (CL) being the most frequent. It manifests as one or a few localized skin ulcers, which can spread to other body areas. Hence, early diagnosis and treatment, typically with pentavalent antimonials, is critical. Traditional diagnostic methods, like parasite culture, microscopy, or the polymerase chain reaction (PCR) for detection of the parasite DNA, have limitations due to the uneven distribution of parasites in biopsy samples. Nonetheless, studies have revealed high levels of parasite-specific anti-α-Gal antibodies in L. (V.) braziliensis-infected patients. Previously, we demonstrated that the neoglycoprotein NGP28b, consisting of the L. (Leishmania) major type-2 glycoinositolphospholipid (GIPL)-3-derived trisaccharide Galpα1,6Galpα1,3Galfß conjugated to bovine serum albumin (BSA) via a linker, acts as a reliable serological biomarker (BMK) for L. (V.) braziliensis infection in Brazil. This indicates the presence of GIPL-3 or a similar structure in this parasite, and its terminal trisaccharide either functions as or is part of an immunodominant glycotope. Here, we explored whether extending the trisaccharide with a mannose unit would enhance its efficacy as a biomarker for the serological detection of L. (V.) braziliensis. We synthesized the tetrasaccharide Galpα1,6Galpα1,3Galfß1,3Manpα(CH2)3SH (G31SH) and conjugated it to maleimide-functionalized BSA to afford NGP31b. When we assessed the efficacy of NGP28b and NGP31b by chemiluminescent enzyme-linked immunosorbent assay on a cohort of CL patients with L. (V.) braziliensis infection from Bolivia and Argentina against a healthy control group, both NGPs exhibited similar or identical sensitivity, specificity, and accuracy. This finding implies that the mannose moiety at the reducing end is not part of the glycotope recognized by the parasite-specific anti-α-Gal antibodies in patients' sera, nor does it exert a relevant influence on the terminal trisaccharide's conformation. Moreover, the mannose does not seem to inhibit glycan-antibody interactions. Therefore, NGP31b is a viable and dependable BMK for the serodiagnosis of CL caused by L. (V.) braziliensis.

WEIRD-Confucian comparisons: Ongoing cultural biases in psychology's evidence base and some recommendations for improving global representation.

The realization that most behavioral science research focuses on cultures labeled as WEIRD-Western, educated, industrialized, rich, and democratic (Arnett, 2008; Henrich et al., 2010; Thalmayer et al., 2021)-has given an impetus to extend the research to more diverse populations. Confucian East Asian societies have relatively strong social and technological infrastructure to advance science and thus have gained much prominence in cross-cultural studies. This has inadvertently fostered another bias: the dominance of WEIRD-Confucian comparisons and a tendency to draw conclusions about "non-WEIRD" cultures in general based on data from Confucian societies. Here, analyzing 1,466,019 scientific abstracts and, separately, coverage of 60 large-scale cross-cultural psychological projects (Nsamples = 2,668 from Ncountries = 153 covering nparticipants = 3,722,940), we quantify the dominance of Confucian over other non-WEIRD cultures in psychological research. Our analysis also reveals the underrepresentation of non-European Union postcommunist societies and the almost total invisibility of Pacific Island, Caribbean, Middle African, and Central Asian societies within the research database of psychology. We call for a shift in cross-cultural studies toward midsize (7+ countries) and ideally large-scale (50+ countries) cross-cultural studies, and we propose mitigations that we believe could aid the inclusion of diverse researchers as well as participants from underrepresented cultures in our field. People in all world regions and cultures deserve psychological knowledge that applies to them. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Assessment of health-related quality of life in patients with Chagas cardiomyopathy using Minnesota living with heart failure questionnaire: A validation study.

OBJECTIVE: Chagas cardiomyopathy (ChC) is the most severe clinical form of Chagas disease and, in association with psychosocial factors, can compromise the health-related quality of life (HRQoL) of affected patients. To date, there is no specific instrument to assess the HRQoL of these patients, and the Minnesota Living with Heart Failure Questionnaire (MLwHFQ), specific for heart failure, is being used both in research and current clinical practice. Therefore, we aimed to verify the validity of the MLwHFQ in the assessment of HRQoL of patients with ChC. METHODS: Fifty patients with ChC (50.6 ± 10.1 years, NYHA I-III) were evaluated. The MLwHFQ, Short-Form of Health Survey (SF-36), Beck Depression Inventory (BDI), and Human Activity Profile (HAP) were applied. All patients underwent echocardiography and Cardiopulmonary Exercise Testing (CPET). RESULTS: The MLwHFQ score correlated with almost all SF-36 domains (with r-value ranging from -0.38 to -0.69), except pain (p = 0.118). The MLwHFQ score also correlated with the BDI score (r = 0.748; p < 0.001), HAP score (r = -0.558; p = 0.001), peak oxygen uptake (r = -0.352; p = 0.01), and left ventricular ejection fraction (r = -0.329; p = 0.021). There was no significant difference in the score found on the MLwHFQ among NYHA classes (p = 0.101), as well as between patients with systolic dysfunction (n = 30) and preserved cardiac function (n = 20) (p = 0.058). Similarly, there was no significant difference in the score found on the physical (p = 0.423) and mental (p = 0.858) components of SF-36 between patients with systolic dysfunction and preserved cardiac function (p = 0.271 and p = 0.609, respectively). There was also no difference in the mental component of SF-36 among NYHA classes (p = 0.673). However, the HRQoL using the physical component of SF-36 was worse in advanced NYHA classes (p = 0.014). CONCLUSION: MLwHF correlated with most SF-36 HRQoL domains, depressive symptoms, physical activity, and systolic function and seems to be valid in assessing the HRQoL of ChC patients.

Avaliação do Conhecimento de Graduandos em Odontologia sobre Lesões Orais Malignas e Desordens Orais Potencialmente Malignas / Evaluation of the Knowledge of Dentistry Graduates about Malignant Oral Lesions and Potentially Malignant Oral Disorders

As alterações orais potencialmente malignas e o câncer oral, quando diagnosticados precocemente, possuem um bom prognóstico. No entanto, a imprecisão nos atendimentos odontológicos dificulta a detecção precoce, fazendo com que o câncer bucal permaneça como um problema de saúde pública atualmente. Objetivo: Avaliar o conhecimento de graduandos em odontologia sobre lesões orais de câncer e alterações orais potencialmente malignas. Método: Os dados foram coletados por meio de um questionário virtual, enviado para graduandos de odontologia de algumas universidades/faculdades localizadas no Estado da Bahia, entre os meses de junho e outubro de 2022. Posteriormente, os dados foram analisados estatisticamente e quatro conceitos foram estabelecidos: A (ótimo nível de informação); B (bom nível de informação); C (nível insatisfatório de informação); e D (péssimo nível de informação). Resultados: A amostra foi composta por 161 estudantes, a maioria entre 20 e 29 anos e do sexo feminino (78,3%). Não houve uma diferença estatística significativa entre os estudantes com até um ano de aprovação em componentes curriculares de estomatologia, patologia ou correlatos, com discentes com mais de um ano de aprovação (p = 0,126). A leucoplasia foi a alteração mais relacionada ao câncer (77%) para os entrevistados, e apenas 23% dos graduandos obtiveram o conceito A; no entanto, 96,9% dos entrevistados possuem interesse em assistir ao curso de educação contínua sobre o assunto. Conclusão: A maioria dos acadêmicos avaliados apresentou um bom nível de informação, entretanto, observou-se que os fatores de risco e a localização das lesões malignas geraram grandes dúvidas nos participantes deste estudo.

Potentially malignant oral disorders and oral cancer in early stages, when diagnosed early, have good prognosis. However, oral cancer is a public health problem today due to imprecision of dental care which makes early detection difficult. Objective: To evaluate the knowledge of dental students about oral cancer lesions and potentially malignant oral disorders. Method: Data were collected through a virtual questionnaire sent to undergraduate dentistry students from some universities/colleges located in the state of Bahia, between June and October 2022. Subsequently, the data were statically analyzed and four concepts were established: A (excellent level of information); B (good level of information); C (unsatisfactory level of information) and D (very poor level of information). Results: The sample consisted of 161 female students (78.3%) mostly between 20 and 29 years old. There was no statistically significant difference between students with up to one year of approval in stomatology, pathology or related disciplines, an students with more than one year of approval (p = 0.126). Leukoplakia was the disorder most related to cancer (77%) and only 23% of undergraduates obtained grade A, however, 96.9% of the respondents are interested in attending a continuing education course on the subject. Conclusion: The majority of the students evaluated had good level of information, nevertheless, the study participants had great doubts about the risk factors and the location of malignant lesions.

Los trastornos orales potencialmente malignos y el cáncer oral en estadios tempranos, cuando se diagnostican a tiempo, tienen un buen pronóstico. Sin embargo, la imprecisión en los tratamientos dentales dificulta la detección previa, por lo que el cáncer bucal sigue siendo un problema de salud pública en la actualidad. Objetivo: Evaluar el conocimiento de los estudiantes de odontología sobre las lesiones orales cancerosas y los trastornos orales potencialmente malignos. Método: Los datos fueron recolectados a través de un cuestionario virtual, enviado a estudiantes de grado en odontología de algunas universidades/facultades ubicadas en el estado de Bahía, entre junio y octubre de 2022. Posteriormente, los datos fueron analizados estadisticamente y se establecieron cuatro conceptos: A (nivel excelente de información); B (buen nivel de información); C (nivel de información insatisfactorio) y D (nivel de información muy bajo). Resultados: La muestra estuvo conformada por 161 estudiantes, la mayoría entre 20 y 29 años y de sexo femenino (78,3%). No hubo diferencia estadísticamente significativa entre estudiantes con hasta un año de aprobación en estomatología, patología o disciplinas afines, con estudiantes con más de un año de aprobación (p=0,126). La leucoplasia fue el trastorno que más se relacionó con el cáncer (77%) y solo el 23% de los estudiantes de pregrado obtuvo la calificación A, sin embargo, el 96,9% de los encuestados está interesado en asistir a un curso de educación continua sobre el tema. Conclusión: La mayoría de los estudiantes evaluados presentaron un buen nivel de información, sin embargo, se observó que los factores de riesgo y la localización de las lesiones malignas generaron grandes dudas entre los participantes de este estudio

Traversing the Cell Wall: The Chitinolytic Activity of Histoplasma capsulatum Extracellular Vesicles Facilitates Their Release.

Histoplasma capsulatum is the causative agent of histoplasmosis. Treating this fungal infection conventionally has significant limitations, prompting the search for alternative therapies. In this context, fungal extracellular vesicles (EVs) hold relevant potential as both therapeutic agents and targets for the treatment of fungal infections. To explore this further, we conducted a study using pharmacological inhibitors of chitinase (methylxanthines) to investigate their potential to reduce EV release and its subsequent impact on fungal virulence in an in vivo invertebrate model. Our findings revealed that a subinhibitory concentration of the methylxanthine, caffeine, effectively reduces EV release, leading to a modulation of H. capsulatum virulence. To the best of our knowledge, this is the first reported instance of a pharmacological inhibitor that reduces fungal EV release without any observed fungicidal effects.

Oncogenic KRASG12D Reprograms Lipid Metabolism by Upregulating SLC25A1 to Drive Pancreatic Tumorigenesis.

Pancreatic cancer is a highly lethal disease with obesity as one of the risk factors. Oncogenic KRAS mutations are prevalent in pancreatic cancer and can rewire lipid metabolism by altering fatty acid (FA) uptake, FA oxidation (FAO), and lipogenesis. Identification of the underlying mechanisms could lead to improved therapeutic strategies for treating KRAS-mutant pancreatic cancer. Here, we observed that KRASG12D upregulated the expression of SLC25A1, a citrate transporter that is a key metabolic switch to mediate FAO, fatty acid synthesis, glycolysis, and gluconeogenesis. In genetically engineered mouse models and human pancreatic cancer cells, KRASG12D induced SLC25A1 upregulation via GLI1, which directly stimulated SLC25A1 transcription by binding its promoter. The enhanced expression of SLC25A1 increased levels of cytosolic citrate, FAs, and key enzymes in lipid metabolism. In addition, a high-fat diet (HFD) further stimulated the KRASG12D-GLI1-SLC25A1 axis and the associated increase in citrate and FAs. Pharmacologic inhibition of SLC25A1 and upstream GLI1 significantly suppressed pancreatic tumorigenesis in KrasG12D/+ mice on a HFD. These results reveal a KRASG12D-GLI1-SLC25A1 regulatory axis, with SLC25A1 as an important node that regulates lipid metabolism during pancreatic tumorigenesis, thus indicating an intervention strategy for oncogenic KRAS-driven pancreatic cancer. SIGNIFICANCE: Upregulation of SLC25A1 induced by KRASG12D-GLI1 signaling rewires lipid metabolism and is exacerbated by HFD to drive the development of pancreatic cancer, representing a targetable metabolic axis to suppress pancreatic tumorigenesis.

Functional predictors of poor outcomes in Chagas cardiomyopathy: The value of end-tidal carbon dioxide at peak exercise.

BACKGROUND: Functional impairment can be detected from the onset of heart disease in patients with Chagas cardiomyopathy (ChC) and the prognostic value of the end-tidal carbon dioxide at peak exercise (PETCO2 peak) should be investigated. OBJECTIVE: To verify the prognostic value of PETCO2 peak in patients with ChC. METHODS: Seventy-six patients with ChC (49.2 ± 9.8 years, NYHA I-III) were evaluated by echocardiography and Cardiopulmonary Exercise Testing. Patients were followed up to four years and the end-point was defined as cardiovascular death, stroke, or cardiac transplantation. RESULTS: At the end of the follow-up period (29.0 ± 16.0 months), 16 patients (21%) had experienced adverse events. The area under the receiver operating characteristic (ROC) curve to identify the risk of adverse events by PETCO2 peak in patients with ChC was 0.83 (95% CI: 0.69 to 0.97), and the value of 32 mmHg was the optimal cut point (70% of sensitivity and 85% of specificity). In the Kaplan-Meier diagram, there was a significant difference (p<0.001) between patients with reduced (≤ 32 mmHg) and preserved PETCO2 peak (>32 mmHg). In the final Cox multivariate model, only reduced PETCO2 peak (HR 4.435; 95% CI: 1.228 to 16.016, p = 0.023) and VO2peak (HR 0.869; 95% CI: 0.778 to 0.971, p = 0.013) remained as independent predictors of poor outcome in ChC patients. CONCLUSION: Reduced PETCO2 peak and VO2peak demonstrated valuable prognostic value in patients with ChC. The cutoff points for both functional variables can be used during risk stratification and may help in the development of therapeutic strategies in ChC patients.

Bruxismo como consequência do estresse pandêmico: revisão integrativa / Bruxism as a consequence of pandemic stress: integrative review

O período pandêmico com todas as suas implicações possibilitou um aumento dos níveis de estresse em parte da população, que teve como consequência a obtenção ou o agravamento do bruxismo. Objetivo: O objetivo deste artigo foi realizar uma revisão integrativa sobre como o estresse causado pela pandemia de COVID-19 influenciou no desenvolvimento do bruxismo, considerando o perfil dos indivíduos acometidos. Realizou-se uma revisão integrativa da literatura a partir da seleção de artigos publicados nas bases de dados BVS, PubMed e EBSCOhost. Para isto, a seguinte questão de pesquisa foi formulada: "Existe relação entre o bruxismo e a pandemia de COVID-19?". A busca objetivou encontrar artigos publicados em português, espanhol e inglês, durante os anos de 2019 a 2023, utilizando os descritores "bruxismo", "COVID-19" e "estresse psicológico" e as suas respectivas versões em inglês, juntamente com a estratégia de busca AND. Revisão de literatura: Vinte estudos foram incluídos, ficando evidente uma prevalência do bruxismo como consequência do estresse pandêmico em pessoas jovens, do sexo feminino, além de estudantes/profissionais da área da saúde. Considerações finais: Acredita-se que a pandemia de COVID-19 vivenciada entre os anos de 2019 e 2023 tenha causado e/ou exacerbado estresse, sendo este um importante fator causador do bruxismo.(AU)

The pandemic period with all its implications allowed an increase in stress levels in part of the population, which resulted in the obstruction or worsening of bruxism. Objective: The aim of this article was to carry out an integrative review on how the stress caused by the COVID-19 pandemic influenced the development of bruxism, considering the profile of affected individuals. Method: An integrative literature review was carried out based on the selection of articles published in the VHL, PubMed and EBSCOhost databases. For this, the following research question was formulated: "Is there a relationship between bruxism and the COVID-19 pandemic?". The search aimed to find articles published in Portuguese, Spanish and English, during the years 2019 to 2023, using the descriptors "bruxism", "COVID-19" and "psychological stress" and their respective versions in English, together with the strategy of search AND. Integratve review: Twenty studies were included, revealing a prevalence of bruxism as a consequence of pandemic stress in young, females, in addition to students/health professionals. Final considerations: It is believed that the COVID-19 pandemic experienced between 2019 and 2023 caused and/or exacerbated stress, which is an important factor causing bruxism.(AU)

Associação entre saúde bucal, variáveis sociais, culturais e de acesso em indivíduos de uma população quilombola / Association between oral health, social, cultural and access variables in individuals from a quilombola population

Avaliar as condições de saúde bucal e sua relação com os aspectos socioculturais e de acesso a serviços odontológicos em quilombolas do Município de Cachoeira (BA). Realizou-se um estudo transversal, examinando 128 indiíduos. A análise estatística foi conduzida através da distribuição das frequências das variáveis demográficas e socioeconômicas. O cálculo de associação entre as variáveis e os desfechos foi obtido pelas Razões de Prevalências e respectivos intervalos de confiança. Constatou-se que há significância estatística (IC 95%) entre a doença periodontal e dieta cariogênica, plantas medicinais e bochecho com chá ou enxaguante bucal, assim como existiu associação entre a cárie dentária e a dificuldade de acesso a serviços odontológicos, odontalgia e o edentulismo. A maior prevalência dos agravos bucais investigados foi em indivíduos adultos e predominantemente em mulheres, sendo que a maior parte dos indivíduos possuía apenas o ensino fundamental e renda inferior a um salário-mínimo.

To evaluate oral health conditions and their relationship with sociocultural aspects and access to dental services in quilombolas in the municipality of Cachoeira, Bahia. A cross-sectional study was carried out, examining 128 individuals. Statistical analysis was conducted through the frequency distribution of demographic and socioeconomic variables. The calculation of the association between variables and outcomes was obtained using Prevalence Ratios and respective confidence intervals. It was found that there is statistical significance (CI 95%) between periodontal disease and cariogenic diet, medicinal plants and mouthwash with tea or mouthwash, as well as an association between dental caries and difficulty in accessing dental services, toothache and edentulism. The highest prevalence of oral diseases investigated was in adult individuals and predominantly in women, and most individuals had only elementary education and income below the minimum wage.

Fatty acid elongases 1-3 have distinct roles in mitochondrial function, growth, and lipid homeostasis in Trypanosoma cruzi.

Trypanosomatids are a diverse group of uniflagellate protozoan parasites that include globally relevant pathogens such as Trypanosoma cruzi, the causative agent of Chagas disease. Trypanosomes lack the fatty acid synthase system typically used for de novo fatty acid (FA) synthesis in other eukaryotes. Instead, these microbes have evolved a modular FA elongase (ELO) system comprised of individual ELO enzymes (ELO1-4) that can operate processively to generate long chain- and very long chain-FAs. The importance of ELO's for maintaining lipid homeostasis in trypanosomatids is currently unclear, given their ability to take up and utilize exogenous FAs for lipid synthesis. To assess ELO function in T. cruzi, we generated individual KO lines, Δelo1, Δelo2, and Δelo3, in which the genes encoding ELO1-3 were functionally disrupted in the parasite insect stage (epimastigote). Using unbiased lipidomic and metabolomic analyses, in combination with metabolic tracing and biochemical approaches, we demonstrate that ELO2 and ELO3 are required for global lipid homeostasis, whereas ELO1 is dispensable for this function. Instead, ELO1 activity is needed to sustain mitochondrial activity and normal growth in T. cruzi epimastigotes. The cross-talk between microsomal ELO1 and the mitochondrion is a novel finding that, we propose, merits further examination of the trypanosomatid ELO pathway as critical for central metabolism.

Craniofacial abnormalities and malocclusion findings in sickle cell disease related to ethnic-racial populations: a critical review of the literature

Introduction: sickle Cell Disease (SCD) is an inherited, hematological, chronic disease that mostly affects racial/ethnic groups. The dental literature discusses SCD's oral symptoms, such as malocclusion and craniofacial abnormalities, without considering the significance of a racial/ethnic perspective. Objective: this article critically reviewed the findings of the studies based on a racial/ethnic standpoint and SCD landmarks. Sources of data: primary and secondary searches selected 146 studies from four scientific literature databases. Two reviewers independently extracted data from eleven included studies. Synthesis of data: most studies used lateral cephalometry and reported craniofacial abnormalities and malocclusions, such as maxillary protrusion, class II skeletal patterns, vertical facial growth patterns, convex facial profile, mandibular retrusion, and the posterior rotation of the jaw. However, there is no mention of racial or ethnic cephalometric patterns to support these findings in the studied populations. In addition, a misunderstanding occurs when overlooking the different periods of growth or ages within and between the studied groups. Furthermore, there is no mention of previous orthodontic treatment. By contrast, there is a lack of information about the medically compromised health status of people with SCD, such as the life period of SCD's diagnosis; the number and timing of blood transfusions; the medical history of hospitalizations, vaso-occlusive crises, or hydroxyurea use. Conclusion: racial and ethnic concerns for the diagnosis of malocclusions and craniofacial anomalies, as well as SCD landmarks, are underappreciated in the examined dental literature. Discarding them also demonstrates institutional racism.

Introdução: a doença falciforme é uma doença hematológica, hereditária, crônica, que afeta principalmente, a população negra, em escala global. Na literatura odontológica, os achados craniofaciais e oclusais relacionados à doença falciforme são discordantes, mas, em comum, desconsideram a perspectiva racial. Objetivo: este artigo revisou criticamente a literatura odontológica e discutiu os achados encontrados na perspectiva racial/étnica. Fonte dos dados: estudos primários e secundários selecionaram 146 ocorrências de quatro bases de dados da literatura científica. Dois revisores extraíram independentemente os dados dos onze estudos incluídos. Síntese dos dados: com base na cefalometria lateral, a maioria dos estudos concluiu que as anormalidades craniofaciais e maloclusões, como protrusão maxilar, padrão esquelético de classe II, padrão de crescimento facial vertical, perfil facial convexo, retrusão mandibular e rotação posterior da mandíbula foram os mais comuns achados para pessoas com doença falciforme. No entanto, ao considerar a perspectiva étnico-racial, não há menção na maioria dos estudos de ajustes dos padrões cefalométricos específicos para as populações racializadas, nem tampouco são consideradas características do grupo populacional e da doença falciforme em si, como sua severidade, o momento de vida em que o diagnóstico ocorreu, número e período de hemotransfusões, internações, crises vaso-oclusivas ou uso de hidroxiureia. Além disso, a ampla faixa etária em diferentes períodos de crescimento ósseo e a ausência de informação sobre tratamento ortodôntico prévio foram observadas. Conclusão: há omissão sobre considerações étnico-raciais para relatar anormalidades craniofaciais e maloclusões sobre doença falciforme na literatura odontológica revisada. Isto pode ser uma expressão do racismo.

Genetic instability in farmers using pesticides: A study in Brazil with analysis combining alkaline comet and micronucleus assays.

The use of pesticides to prevent and control pests also increases food production. Pesticides are widely used by contemporary farmers, especially in Brazil, where the economy is based on agriculture. The objective of this study was to evaluate the genotoxic potential of pesticide use in rural workers in Maringá, Paraná, Brazil. DNA damage in whole blood cells was measured by the comet assay, while the frequency of cell types, abnormalities, and nuclear damage was estimated using the buccal micronucleus cytome assay. Samples of buccal mucosa were collected from 50 male volunteers (27 not exposed to pesticides and 23 occupationally exposed to pesticides). Among them, 44 volunteered for blood sampling (24 unexposed and 20 exposed). In the comet assay, the exposed farmers had a higher damage index than non-exposed ones. There were also statistically significant differences between the groups in the buccal micronucleus cytome assay. Farmers exhibited an increase in basal cell numbers, and cytogenetic alterations, represented by condensed chromatin and karyolitic cells. Comparisons between cell morphologies and epidemiological factors indicated an increased number of condensed chromatin and karyolitic cells in individuals who were responsible for preparation and transportation of pesticides to agricultural machines. Thus, the participants in this study who were exposed to pesticides were more sensitive to genetic damage, and thereby, more susceptible to diseases resulting from such damage. These results demonstrated that health policies should be developed for pesticide-exposed farmers to better mitigate risks and damage to their health.

The Trypanosoma brucei MISP family of invariant proteins is co-expressed with BARP as triple helical bundle structures on the surface of salivary gland forms, but is dispensable for parasite development within the tsetse vector.

Trypanosoma brucei spp. develop into mammalian-infectious metacyclic trypomastigotes inside tsetse salivary glands. Besides acquiring a variant surface glycoprotein (VSG) coat, little is known about the metacyclic expression of invariant surface antigens. Proteomic analyses of saliva from T. brucei-infected tsetse flies identified, in addition to VSG and Brucei Alanine-Rich Protein (BARP) peptides, a family of glycosylphosphatidylinositol (GPI)-anchored surface proteins herein named as Metacyclic Invariant Surface Proteins (MISP) because of its predominant expression on the surface of metacyclic trypomastigotes. The MISP family is encoded by five paralog genes with >80% protein identity, which are exclusively expressed by salivary gland stages of the parasite and peak in metacyclic stage, as shown by confocal microscopy and immuno-high resolution scanning electron microscopy. Crystallographic analysis of a MISP isoform (MISP360) and a high confidence model of BARP revealed a triple helical bundle architecture commonly found in other trypanosome surface proteins. Molecular modelling combined with live fluorescent microscopy suggests that MISP N-termini are potentially extended above the metacyclic VSG coat, and thus could be tested as a transmission-blocking vaccine target. However, vaccination with recombinant MISP360 isoform did not protect mice against a T. brucei infectious tsetse bite. Lastly, both CRISPR-Cas9-driven knock out and RNAi knock down of all MISP paralogues suggest they are not essential for parasite development in the tsetse vector. We suggest MISP may be relevant during trypanosome transmission or establishment in the vertebrate's skin.

Treatment with benznidazole and pentoxifylline regulates microRNA transcriptomic profile in a murine model of Chagas chronic cardiomyopathy.

Chronic Chagas cardiomyopathy (CCC) is one of the leading causes of morbidity and mortality due to cardiovascular disorders in endemic areas of Chagas disease (CD), a neglected tropical illness caused by the protozoan parasite Trypanosoma cruzi. CCC is characterized by parasite persistence and inflammatory response in the heart tissue, which occur parallel to microRNA (miRNA) alterations. Here, we investigated the miRNA transcriptome profiling in the cardiac tissue of chronically T. cruzi-infected mice treated with a suboptimal dose of benznidazole (Bz), the immunomodulator pentoxifylline alone (PTX), or the combination of both (Bz+PTX), following the CCC onset. At 150 days post-infection, Bz, PTX, and Bz+PTX treatment regimens improved electrocardiographic alterations, reducing the percentage of mice afflicted by sinus arrhythmia and second-degree atrioventricular block (AVB2) when compared with the vehicle-treated animals. miRNA Transcriptome profiling revealed considerable changes in the differential expression of miRNAs in the Bz and Bz+PTX treatment groups compared with the control (infected, vehicle-treated) group. The latter showed pathways related to organismal abnormalities, cellular development, skeletal muscle development, cardiac enlargement, and fibrosis, likely associated with CCC. Bz-Treated mice exhibited 68 differentially expressed miRNAs related to signaling pathways like cell cycle, cell death and survival, tissue morphology, and connective tissue function. Finally, the Bz+PTX-treated group revealed 58 differentially expressed miRNAs associated with key signaling pathways related to cellular growth and proliferation, tissue development, cardiac fibrosis, damage, and necrosis/cell death. The T. cruzi-induced upregulation of miR-146b-5p, previously shown in acutely infected mice and in vitro T. cruzi-infected cardiomyocytes, was reversed upon Bz and Bz+PTX treatment regimens when further experimentally validated. Our results further our understanding of molecular pathways related to CCC progression and evaluation of treatment response. Moreover, the differentially expressed miRNAs may serve as drug targets, associated molecular therapy, or biomarkers of treatment outcomes.

Synthesis and Photoreactivity of 7-Nitroindoline-S-thiocarbamates.

The photolytic properties of N-acyl-7-nitroindolines make these compounds attractive as photocleavable protecting groups and "caged" compounds for the light-induced release ("uncaging") of biologically active compounds and as acylating reagents under neutral conditions. However, the synthesis of N-acyl-7-nitroindolines usually requires multiple steps, and the direct acylation of 7-nitroindolines can be quite challenging. 7-Nitroindolines with other types of N-carbonyl-containing groups may also be photoreactive and could potentially be better accessible. Here we demonstrate the short and efficient synthesis of 5-bromo-7-nitroindoline-S-thiocarbamates, a new class of photoreactive compounds, and the study of some of their photochemical and photophysical properties. Using 5-bromo-7-nitroindoline-S-ethylthiocarbamate as a model compound, we show that it can undergo one-photon and two-photon photolysis at 350 and 710 nm, respectively. Our experimental data and quantum chemistry calculations support a photolysis pathway that differs from photolysis pathways previously reported for N-acyl-7-nitroindolines. The photolysis with 350 nm light results in 5-bromo-7-nitrosoindoline, which is in equilibrium with its dimeric form(s), as supported by experiment and theory. This study expands the scope of photoreactive 7-nitroindoline derivatives and informs the development of novel photocleavable compounds.

Toxicogenic effects of the mushroom Ganoderma lucidum on human liver and kidney tumor cells and peripheral blood lymphocytes.

ETHNOPHARMACOLOGICAL RELEVANCE: Ganoderma lucidum (Curtis) P. Karst., a bioactive mushroom with medicinal properties, is known to exert immunomodulatory, anti-inflammatory, hypocholesterolemic, hypoglycemic, and hepatoprotective effects. AIM OF THE STUDY: In this study, the effects of the G. lucidum fruiting body dry extract (GLE) on human liver (HepG2/C3A) and kidney (786-O) tumor cells and peripheral blood lymphocytes were evaluated. MATERIALS AND METHODS: MTT-based cytotoxicity, trypan blue-based cell viability, comet, and cytokinesis-block micronucleus cytome assays were performed, and the production of reactive oxygen species was evaluated in vitro. RESULTS: GLE was toxic to the tumor cells, decreasing their viability by increasing their production of reactive oxygen species and inducing damage to their DNA. By contrast, only high concentrations of GLE were toxic to lymphocytes and decreased their viability, whereas low concentrations increased lymphocyte viability. Moreover, primary DNA damage was induced by GLE only at the highest concentration tested. CONCLUSIONS: G. lucidum shows potential antitumor effects against cancerous kidney and liver cells, exhibiting cytotoxic and genotoxic activity at low concentrations, whereas the same effects in lymphocytes are mediated only at high concentrations. This mushroom has the potential to be biotechnologically developed into a therapeutic agent for diseases, such as cancer.

Development of SEDDS formulation containing caffeine for dermal delivery.

OBJECTIVE: The objective of this work was to develop a self-emulsifying drug delivery system (SEDDS) containing caffeine for the treatment of cellulite. METHODS: SEDDS were prepared using the solution method. 0.5% (w/v) caffeine was added to the previously selected excipients. The system was characterized by droplet size, zeta potential, emulsification time and long-term stability. In vitro release and skin permeation were investigated using Franz-type diffusion cells. The cytotoxicity was evaluated on normal human keratinocytes. RESULTS: Caffeine SEDDS were thermodynamically stable, with a zeta potential less than - 22 mV and droplet size around 30 nm, and were long-term stable. The permeation study showed that the formulation promoted caffeine accumulation in the skin layers, suggesting an increase in local circulation. Cytotoxicity studies on HaCaT cells were not conclusive as the surfactant used indicated false-positive results due to its high molar mass. CONCLUSION: It was possible to obtain a stable SEDDS that could cause an increase in blood flow in the applied area, resulting in cellulite reduction.

OBJECTIF: L'objectif de ce travail était de développer un système d'administration de médicaments auto-émulsifiants (SEDDS) contenant de la caféine pour le traitement de la cellulite. MÉTHODES: Les SEDDS ont été préparés par la méthode en solution. 0,5 % (p/v) de caféine a été ajouté aux excipients préalablement sélectionnés. Le système a été caractérisé par la taille des gouttelettes, le potentiel zêta, le temps d'émulsification et la stabilité à long terme. La libération in vitro et la perméation cutanée ont été étudiées dans des cellules de diffusion de type Franz. La cytotoxicité était évaluée sur des kératinocytes humains normaux. RÉSULTATS: Les SEDDS de caféine étaient thermodynamiquement stables, avec un potentiel Zeta inférieur à -22 mV et une taille de gouttelettes d'environ 30 nm, et stables à long terme. L'étude de perméation a montré que les formulations favorisent l'accumulation de caféine dans les couches de la peau, suggérant une augmentation de la circulation locale. Les études de cytotoxicité sur les cellules HaCaT n'ont pas été concluantes car le surfactant utilisé indique des résultats faussement positifs dus à une masse molaire élevée. CONCLUSION: Il a été possible d'obtenir un SEDDS stable qui peut provoquer une augmentation du flux sanguin dans la zone appliquée, entraînant une réduction de la cellulite.