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1.
Dev Psychol ; 2024 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-38661663

RESUMO

Maternal smoking during pregnancy (MSDP) may impact offspring biological (e.g., deoxyribonucleic acid methylation [DNAm]) and behavioral (e.g., attention-deficit/hyperactivity disorder hyperactive/impulsive [ADHD-HI] symptoms) development. There has been consistency in findings of differential methylation in global DNAm, and the specific genes AHRR, CYP1A1, CNTNAP2, MYO1G, and GFI1 in relation to MSDP. The current study aims to (a) replicate the associations of MSDP and DNAm in prior literature in middle childhood-adolescence (cross-sectionally) using a sibling-comparison design where siblings were discordant for MSDP (n = 328 families; Mage Sibling 1 = 13.02; Sibling 2 = 10.20), adjusting for prenatal and postnatal covariates in order to isolate the MSDP exposure on DNAm. We also (b) cross-sectionally explored the role of DNAm in the most robust MSDP-ADHD associations (i.e., with ADHD-HI) previously found in this sample. We quantified smoking exposure severity for each sibling reflecting time and quantity of MSDP, centered relative to the sibling pair's average (i.e., within-family centered, indicating child-specific effects attributable MSDP exposure) and controlling for the sibling average MSDP (i.e., between-family component, indicating familial confounding related to MSDP). We found that child-specific MSDP was associated with global DNAm, and CNTNAP2, CYP1A1, and MYO1G methylation after covariate adjustment, corroborating emerging evidence for a potentially causal pathway between MSDP and DNAm. There was some evidence that child-specific CNTNAP2 and MYO1G methylation partially explained associations between MSDP and ADHD-HI symptoms, though only on one measure (of two). Future studies focused on replication of these findings in a longitudinal genetic design could further solidify the associations found in the current study. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

3.
Pharmaceutics ; 16(2)2024 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-38399316

RESUMO

Toxoplasmosis is a globally prevalent zoonotic disease with significant clinical implications, including neurotoxoplasmosis, a leading cause of cerebral lesions in AIDS patients. The current pharmacological treatments for toxoplasmosis face clinical limitations, necessitating the urgent development of new therapeutics. Natural sources have yielded diverse bioactive compounds, serving as the foundation for clinically used derivatives. The exploration of marine bacteria-derived natural products has led to marinoquinolines, which feature a pyrroloquinoline core and demonstrate in vitro and in vivo anti-Plasmodium activity. This study investigates the in vitro anti-Toxoplasma gondii potential of six marinoquinoline derivatives. Additionally, it conducts absorption, distribution, metabolism, excretion, and toxicity (ADMET) predictions, and evaluates the in vivo efficacy of one selected compound. The compounds displayed half-maximal effective concentration (EC50) values between 1.31 and 3.78 µM and half-maximal cytotoxic concentration (CC50) values ranging from 4.16 to 30.51 µM, resulting in selectivity indices (SI) from 3.18 to 20.85. MQ-1 exhibiting the highest in vitro SI, significantly reduced tachyzoite numbers in the peritoneum of RH-infected Swiss mice when it was orally administered at 12.5 mg/kg/day for eight consecutive days. Also, MQ-1 significantly reduced the cerebral parasite burden in chronically ME49 infected C57BL/6 mice when it was orally administered at 25 mg/kg/day for 10 consecutive days. These findings underscore the promising anti-T. gondii activity of marinoquinolines and their potential as novel therapeutic agents against this disease.

4.
Acta Trop ; 252: 107141, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38342286

RESUMO

The impact of diet composition and energy content on schistosomiasis evolution and treatment efficacy is still controversial. This study compared the impact of sucrose-rich diet and intermittent fasting on Schistosoma mansoni infection and praziquantel (PZQ)-based chemotherapy response in mice. BALB/c mice were infected with S. mansoni and followed for 15 weeks. The animals were randomized into nine groups receiving high glycemic load (high-sucrose diet - HSD), low caloric load (standard chow alternate-day fasting - ADF), and standard chow ad libitum (AL). Eight weeks after S. mansoni infection, these groups remained untreated or were treated with PZQ (300 mg/kg/day) for 3 days. Our results indicated that parasite load (S. mansoni eggs and parasite DNA levels), granulomatous inflammation (granulomas number and size), and liver microstructural damage (reduction in hepatocytes number, increase in nucleus-cytoplasm ratio, connective stroma expansion and fibrosis) were increased in ADF-treated animals. These animals also showed decreased eggs retention, granulomatous inflammation and collagen accumulation in the small intestine. Conversely, HSD diet and PZQ treatment attenuated all these parameters and stimulated hepatic regenerative response. PZQ also stimulated fibrosis resolution in HSD-treated mice, effect that was limited ADF-exposed mice. Our findings indicate that dietary glycemic and energy load can modulate schistosomiasis progression and the severity of hepatic and intestinal granulomatous inflammation in untreated and PZQ-treated mice. Thus, lower intestinal eggs retention may potentially be linked to worsening liver disease in ADF, while attenuation of hepatic and intestinal granulomatous inflammation is consistent with reduced parasite load in HSD- and PZQ-treated animals.


Assuntos
Anti-Helmínticos , Hepatopatias , Esquistossomose mansoni , Esquistossomose , Animais , Camundongos , Schistosoma mansoni , Antiparasitários/uso terapêutico , Praziquantel/farmacologia , Esquistossomose mansoni/tratamento farmacológico , Esquistossomose mansoni/parasitologia , Fígado/parasitologia , Esquistossomose/tratamento farmacológico , Inflamação/tratamento farmacológico , Fibrose , Dieta , Sacarose/farmacologia , Sacarose/uso terapêutico , Anti-Helmínticos/uso terapêutico
5.
PeerJ ; 12: e16705, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38282865

RESUMO

Reef crests in the Caribbean have lost approximately 80% of the foundational habitat-forming coral Acropora palmata (Lamarck, 1816), with declines registered as early as the 1950s mainly from anthropogenic causes. We studied two reef crests in the northwestern region of Cuba over 17 years (2005 to 2021) to evaluate temporal changes in coral cover, dominated by A. palmata, and their potential drivers. The density of A. palmata generally showed a negative trend at both reefs, with the lowest density recorded in 2021 at 0.2 ± 0.05 col. m-2 at Playa Baracoa and 1.0 ± 0.1 col. m-2 at Rincon de Guanabo. The mean size of the colonies in the two reefs also decreased over time. In Playa Baracoa, the mean diameter of A. palmata colonies decreased from 2012 at 67 ± 5.9 cm to 2013 at 34 ± 2.2 cm, whereas in Rincon de Guanabo, a change in diameter was evident from 2015 at 44.3 ± 2.3 to 2021 at 21.6 ± 0.9 cm. Adult colonies (10 cm-50 cm diameter) predominated in most years on both reefs. The populations of A. palmata on both reefs were healthy, with an average of 70% colonies in good condition during the study period. However, A. palmata cover decreased by almost half by 2021, to 8.6% in Playa Baracoa and 16.8% in Rincon de Guanabo. By contrast, macroalgal cover increased two-fold to 87.1% in Playa Baracoa and four-fold to 77.2% in Rincon de Guanabo. The density of the sea urchin Diadema antillarum was higher in Playa Baracoa than in Rincon de Guanabo. The highest densities were 2.8 ± 0.2 ind. m-2 in Playa Baracoa in 2005 and 0.1 ± 0.03 ind. m-2 in Rincon de Guanabo in 2008. Although our results show an overall decline of A. palmata (density and percent cover) and an increase in macroalgae, these two reef crests are in better condition than most reefs in the Caribbean in terms of the density and health of A. palmata populations, and the density of D. antillarum at Playa Baracoa. Our results are important in establishing a management plan to ensure the condition of these reef crests does not degrade further.


Assuntos
Antozoários , Animais , Cuba , Ecossistema , Ouriços-do-Mar , Região do Caribe
6.
Artigo em Inglês | MEDLINE | ID: mdl-38177334

RESUMO

BACKGROUND: Humans are exposed to phthalates, a class of non-persistent chemicals, through multiple products, including personal care and cosmetics. Associations between specific phthalates and product use have been inconsistent. However, determining these connections could provide avenues for exposure reduction. OBJECTIVE: Examine the association between patterns of personal care product use and associations with phthalate and replacement biomarkers. METHODS: In the Human Placenta and Phthalates Study, 303 women were enrolled in early pregnancy and followed for up to 8 visits across gestation. At each visit, women completed a questionnaire about product use in the prior 24 hours and contributed urine samples, subsequently analyzed for 18 phthalate and replacement metabolites. At early, mid-, and late pregnancy, questionnaire responses were condensed and repeated metabolite concentrations were averaged. Latent class analysis (LCA) was used to determine groups of women with similar use patterns, and weighted associations between group membership and biomarker concentrations were assessed. RESULTS: LCA sorted women into groups which largely corresponded to: (1) low fragranced product use (16-23% of women); (2) fragranced product and low body wash use (22-26%); 3) fragranced product and low bar soap use (26-51%); and (4) low product use (7-34%). Monoethyl phthalate (MEP) urinary concentrations were 7-10% lower and concentrations of summed di(2-ethylhexyl) terephthalate metabolites were 15-21% lower among women in the "low fragranced product use" group compared to the population mean. Few other consistent associations between group and biomarker concentrations were noted. IMPACT STATEMENT: Personal care products and cosmetics are a known exposure source for phthalates and potentially represent one of the most accessible intervention targets for exposure reduction. However, in this analysis accounting for concurrent use and fragranced status of products, we did not find any use patterns that corresponded to universally lower levels.

7.
Arq Gastroenterol ; 60(4): 419-430, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38018547

RESUMO

BACKGROUND: Diet is one of the most important modifiable risk factors for the incidence of gastric cancer. OBJECTIVE: To carry out an exploratory analysis on the dietary patterns of individuals with gastric adenocarcinoma (AdG) in the Central Brazil region. METHODS: This is a case-control study carried out from April 2019 to July 2022, in three reference centers for cancer treatment in Goiânia-GO. The cases were patients diagnosed with AdG, the control 1 dyspeptic patients submitted to upper digestive endoscopy and the control 2 patients without gastric complaints. In the three groups, patients aged 18 to 75 years and of both sexes were recruited. To assess food consumption, a Food Frequency Questionnaire validated for the Brazilian population was used. Dietary patterns were identified by Exploratory Factor Analysis (EFA), using principal component analysis as the extraction method, followed by Varimax rotation. RESULTS: The commonality values in the EFA for the foods/food groups consumed by the cases and controls were above 0.30 for all variables. The variance explained by the model was 66.7% for cases, 60.3% for control 1 and 59.7% for control 2. Three eating patterns were identified in cases, control 1 and control 2 that explained 34, 87%, 35.41% and 33.25% respectively of the total variance. The first pattern ("healthy") was characterized by the consumption of vegetables, fruits, meat and cheese; the second ("unhealthy") for sausages, pizzas, snacks, ketchup, sweet drinks and instant noodles and the third ("prudent") rice, beans, meat and fried fish and pasta. CONCLUSION: This study identified three dietary patterns among patients with AdG and controls in the Central Brazil region. According to the identified patterns, it will be possible to establish a relationship between diet and other epidemiological measures aimed at the prevention of gastric cancer.


Assuntos
Adenocarcinoma , Neoplasias Gástricas , Masculino , Feminino , Humanos , Brasil/epidemiologia , Neoplasias Gástricas/epidemiologia , Estudos de Casos e Controles , Dieta , Comportamento Alimentar , Adenocarcinoma/epidemiologia
8.
Arq. gastroenterol ; 60(4): 419-430, Oct.-Nov. 2023. tab, graf
Artigo em Inglês | LILACS-Express | LILACS | ID: biblio-1527865

RESUMO

ABSTRACT Background: Diet is one of the most important modifiable risk factors for the incidence of gastric cancer. Objective: To carry out an exploratory analysis on the dietary patterns of individuals with gastric adenocarcinoma (AdG) in the Central Brazil region. Methods: This is a case-control study carried out from April 2019 to July 2022, in three reference centers for cancer treatment in Goiânia-GO. The cases were patients diagnosed with AdG, the control 1 dyspeptic patients submitted to upper digestive endoscopy and the control 2 patients without gastric complaints. In the three groups, patients aged 18 to 75 years and of both sexes were recruited. To assess food consumption, a Food Frequency Questionnaire validated for the Brazilian population was used. Dietary patterns were identified by Exploratory Factor Analysis (EFA), using principal component analysis as the extraction method, followed by Varimax rotation. Results: The commonality values in the EFA for the foods/food groups consumed by the cases and controls were above 0.30 for all variables. The variance explained by the model was 66.7% for cases, 60.3% for control 1 and 59.7% for control 2. Three eating patterns were identified in cases, control 1 and control 2 that explained 34, 87%, 35.41% and 33.25% respectively of the total variance. The first pattern ("healthy") was characterized by the consumption of vegetables, fruits, meat and cheese; the second ("unhealthy") for sausages, pizzas, snacks, ketchup, sweet drinks and instant noodles and the third ("prudent") rice, beans, meat and fried fish and pasta. Conclusion: This study identified three dietary patterns among patients with AdG and controls in the Central Brazil region. According to the identified patterns, it will be possible to establish a relationship between diet and other epidemiological measures aimed at the prevention of gastric cancer.


RESUMO Contexto: A dieta é um dos fatores de risco modificáveis mais importante para a incidência de câncer gástrico. Objetivo: Realizar uma análise exploratória sobre os padrões alimentares de indivíduos com adenocarcinoma gástrico (AdG) na região Brasil central. Métodos: Este é um estudo de caso-controle realizado no período de abril de 2019 a julho de 2022, em três centros de referência para o tratamento para câncer em Goiânia-GO. Os casos foram pacientes diagnosticados com AdG, o controle 1 pacientes dispépticos submetidos a endoscopia digestiva alta e o controle 2 pacientes sem queixas gástricas. Nos três grupos foram recrutados pacientes de 18 a 75 anos e de ambos os sexos. Para avaliar o consumo alimentar foi utilizado um Questionário de Frequência Alimentar validado para a população brasileira. Os padrões alimentares foram identificados por Análise Fatorial Exploratória (AFE), utilizando a análise de componentes principais como método de extração, seguida pela rotação Varimax. Resultados: Os valores de comunalidade na AFE para os alimentos/grupos alimentares consumidos pelos casos e controles ficaram acima de 0,30 para todas as variáveis. A variância explicada pelo modelo foi de 66,7%, para casos, 60,3% para o controle 1 e 59,7% para o controle 2. Foram identificados três padrões alimentares nos casos, controle 1 e controle 2 que explicaram 34,87%, 35,41% e 33,25% respectivamente da variância total. O primeiro padrão ("saudável") foi caracterizado pelo consumo de vegetais, frutas, carne e queijos; o segundo ("não saudável") por embutidos, pizzas, snacks, ketchup, bebidas doces e macarrão instantâneo e o terceiro ("prudente") arroz, feijão, carnes e peixes fritos e massas. Conclusão: Esse estudo identificou três padrões alimentares entre os pacientes com AdG e os controles na região Brasil central. De acordo com os padrões identificados, será possível estabelecer uma relação entre a dieta e outras medidas epidemiológicas destinadas à prevenção do câncer gástrico.

9.
Nursing (Ed. bras., Impr.) ; 26(305): 9973-9977, nov.2023. tab
Artigo em Inglês, Português | LILACS, BDENF - Enfermagem | ID: biblio-1526237

RESUMO

Avaliar a eficácia do TEGUM® versus produto já utilizado na instituição na prevenção de radiodermites. Método: Estudo prospectivo, quantitativo, do tipo descritivo-exploratório em um hospital oncológico. O projeto foi aprovado pelo Comitê de Ética em Pesquisa com o CAAE: 24278319.8.0000.0099. Resultados: Dos 88 pacientes, 96,6% tinham câncer de mama. Em média os pacientes passaram por 25 aplicações de radioterapia, sendo 92% tratados em acelerador linear e 8% em cobalto. Dos 88 pacientes, tivemos 51,1% no Braço 1 (produto à base de Aloe Vera) e 48,9% no Braço 2 (Tegum®), e após levantamento a prevenção de radiodermite foi efetiva em 70,5% dos pacientes em ambos os braços. Conclusão: Concluímos que é necessária a prevenção, visando a redução das radiodermites nos pacientes submetidos a radioterapia. Além de mais estudos que possam definir melhor essa reação, melhorando a qualidade de vida durante e após o término do tratamento oncológico.(AU)


TTo evaluate the effectiveness of TEGUM® versus the product already used in the institution in preventing radiodermatitis. Method: Prospective, quantitative, descriptive-exploratory study in an oncology hospital. The project was approved by the Research Ethics Committee with CAAE: 24278319.8.0000.0099. Results: Of the 88 patients, 96.6% had breast cancer. On average, patients underwent 25 radiotherapy applications, with 92% treated with linear accelerator and 8% with cobalt. Of the 88 patients, we had 51.1% in Arm 1 (Aloe Vera-based product) and 48.9% in Arm 2 (Tegum®), and after survey the prevention of radiodermatitis was effective in 70.5% of patients in both arms. Conclusion: We conclude that prevention is necessary, aiming to reduce radiodermatitis in patients undergoing radiotherapy. In addition to more studies that can better define this reaction, improving quality of life during and after the end of cancer treatment.(AU)


Evaluar la efectividad de TEGUM® versus el producto ya utilizado en la institución para prevenir la radiodermatitis. Método: Estudio prospectivo, cuantitativo, descriptivo-exploratorio en un hospital de oncología. El proyecto fue aprobado por el Comité de Ética en Investigación con CAAE: 24278319.8.0000.0099. Resultados: De las 88 pacientes, el 96,6% presentó cáncer de mama. En promedio, los pacientes se sometieron a 25 aplicaciones de radioterapia, de las cuales el 92% fueron tratados con acelerador lineal y el 8% con cobalto. De los 88 pacientes, teníamos el 51,1 % en el grupo 1 (producto a base de aloe vera) y el 48,9 % en el grupo 2 (Tegum®), y después de la encuesta, la prevención de la radiodermatitis fue efectiva en el 70,5 % de los pacientes en ambos grupos. Conclusión: Concluimos que la prevención es necesaria, teniendo como objetivo reducir la radiodermatitis en pacientes sometidos a radioterapia. Además de más estudios que puedan definir mejor esta reacción, mejorando la calidad de vida durante y después de finalizar el tratamiento contra el cáncer.(AU)


Assuntos
Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Radiodermite , Pele , Enfermagem Ambulatorial , Oncologia
10.
Parasitology ; 150(13): 1226-1235, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37859414

RESUMO

Toxoplasmosis is a significant public health concern with limited therapeutic options. The medicines for malaria venture (MMV) developed the pandemic response box (PRB) containing 400 drug-like molecules with broad pathogen activity. The aim of this work is to evaluate PRB compounds for their anti-Toxoplasma gondii activity and identify promising candidates for further evaluation. Screening identified 42 selective compounds with half effective concentration (EC50) ranging from 2.4 to 913.1 nm and half cytotoxic concentration (CC50) ranging from 6 µm to >50 µm. Selectivity index (SI) values (CC50/EC50) ranged from 11 to 17 708. Based on its in silico and in vitro profile and its commercial availability, RWJ-67657 was selected for further studies. Molecular docking analysis showed RWJ-67657 is predicted to bind to T. gondii p38 mitogen-activated protein kinase (TgMAPK). Oral administration of RWJ-67657 (20 mg kg day−1/10 days) significantly reduced parasite burden in chronically infected mice compared to mock-treated group (P < 0.01). These findings highlight the PRB as a promising source for anti-T. gondii compounds, with several showing favourable drug properties, including MMV1634492, MMV002731, MMV1634491, MMV1581551, MMV011565, MMV1581558, MMV1578577, MMV233495 and MMV1580482, firstly described here as anti-T. gondii agents. RWJ-67657 emerges as a valuable drug candidate for experimental chronic cerebral toxoplasmosis therapy.


Assuntos
Malária , Toxoplasma , Animais , Camundongos , Simulação de Acoplamento Molecular , Pandemias
11.
Psicol. rev ; 32(1): 191-212, 17/10/2023.
Artigo em Português | LILACS, Index Psicologia - Periódicos | ID: biblio-1518338

RESUMO

A pandemia da COVID-19 resultou em grande estresse, especialmente para populações mais vulneráveis, como mulheres grávidas e no pós-parto. Devido ao isolamento social, durante o início do período pandêmico, as redes sociais tornaram-se recursos importantes para informar e promover saúde e bem--estar. O objetivo deste estudo é apresentar uma proposta psicoeducativa de intervenção positiva na forma de posts para o Instagram e sua validade de conteúdo para o enfrentamento do estresse provocado pela pandemia por gestantes e puérperas no ano de 2020. A validade de conteúdo foi avaliada por 64 juízas, que analisaram 29 posts adotando uma escala Likert de 5 pontos para validar linguagem, relevância, pertinência e apresentação da proposta. Observou-se coeficientes de validade de conteúdo acima do ponto de corte (≥ 0.80) para todos os critérios, o que indica a adequação da proposta para enfrentar os estressores da pandemia pela população alvo. Dessa forma, confirmou-se a possibilidade de utilização das mídias sociais visando o aumento no acesso a materiais de qualidade que promovem a democratização do cuidado à saúde mental. (AU)


The COVID-19 pandemic has induced significant stress, particularly among vulnerable populations, such as pregnant and postpartum women. Given the social isolation measures implemented at the onset of the pandemic, social media has emerged as a vital tool for disseminating health information and promoting well-being. This study aims to present a psychoeducational inter-vention proposal in the form of Instagram posts and assess its content validity in addressing pandemic-induced stress among pregnant and postpartum women in the year 2020. Content validity was evaluated by 64 female judges who assessed 29 posts using a 5-point Likert scale to validate language, relevance, pertinence, and presentation of the proposal. Results indicated content validity coefficients exceeding the established threshold (≥ 0.80) for all criteria, affirming the suitability of the proposal for mitigating pandemic--related stressors among the target population. Thus, the utilization of social media to enhance access to high-quality resources promoting mental health care democratization is confirmed. (AU)


La pandemia de COVID-19 resultó en un gran estrés, especialmente para pobla-ciones más vulnerables, como mujeres embarazadas y postparto. Debido al aislamiento social durante el periodo pandémico, las redes sociales se volvieron en recursos importantes para informar y promover la salud y el bienestar. El objetivo del estudio es presentar una propuesta psicoeducativa de inter-vención positiva en forma de posts para Instagram y su validez de contenido para el enfrentamiento del estrés provocado por la pandemia por gestantes y puérperas en el año de 2020. La validez del contenido fue evaluada por 64 jueces, que analizaron 29 posts adoptando una escala Likert de 5 puntos para validar lenguaje, relevancia, pertinencia y presentación de la propuesta. Se observaron coeficientes de validez de contenido por encima del punto de corte (≥ 0.80) para todos los criterios, lo que indica la adecuación de la propuesta para enfrentar los estresores de la pandemia por parte de la población obje-tivo. Así, sabemos que es posible utilizar las redes sociales para incrementar el acceso a materiales de calidad que promuevan la democratización de la atención de la salud. (AU)


Assuntos
Humanos , Feminino , Gravidez , Adulto , Isolamento Social/psicologia , Gestantes/psicologia , Mídias Sociais , Promoção da Saúde/métodos , Adaptação Psicológica , Saúde Mental , Intervenção Baseada em Internet , Angústia Psicológica , COVID-19/psicologia , Métodos
12.
PLoS One ; 18(7): e0288335, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37418497

RESUMO

Toxoplasmosis, caused by the obligate intracellular parasite Toxoplasma gondii, affects about one-third of the world's population and can cause severe congenital, neurological and ocular issues. Current treatment options are limited, and there are no human vaccines available to prevent transmission. Drug repurposing has been effective in identifying anti-T. gondii drugs. In this study, the screening of the COVID Box, a compilation of 160 compounds provided by the "Medicines for Malaria Venture" organization, was conducted to explore its potential for repurposing drugs to combat toxoplasmosis. The objective of the present work was to evaluate the compounds' ability to inhibit T. gondii tachyzoite growth, assess their cytotoxicity against human cells, examine their absorption, distribution, metabolism, excretion, and toxicity (ADMET) properties, and investigate the potential of one candidate drug through an experimental chronic model of toxoplasmosis. Early screening identified 29 compounds that could inhibit T. gondii survival by over 80% while keeping human cell survival up to 50% at a concentration of 1 µM. The Half Effective Concentrations (EC50) of these compounds ranged from 0.04 to 0.92 µM, while the Half Cytotoxic Concentrations (CC50) ranged from 2.48 to over 50 µM. Almitrine was chosen for further evaluation due to its favorable characteristics, including anti-T. gondii activity at nanomolar concentrations, low cytotoxicity, and ADMET properties. Administering almitrine bismesylate (Vectarion®) orally at dose of 25 mg/kg/day for ten consecutive days resulted in a statistically significant (p < 0.001) reduction in parasite burden in the brains of mice chronically infected with T. gondii (ME49 strain). This was determined by quantifying the RNA of living parasites using real-time PCR. The presented results suggest that almitrine may be a promising drug candidate for additional experimental studies on toxoplasmosis and provide further evidence of the potential of the MMV collections as a valuable source of drugs to be repositioned for infectious diseases.


Assuntos
COVID-19 , Malária , Toxoplasma , Toxoplasmose , Animais , Camundongos , Almitrina/farmacologia , Almitrina/uso terapêutico , Reposicionamento de Medicamentos , Toxoplasmose/tratamento farmacológico , Toxoplasmose/parasitologia
13.
Therap Adv Gastroenterol ; 16: 17562848231160620, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37324320

RESUMO

Background: Helicobacter pylori (H. pylori) is a group 1 carcinogen and the etiological agent of gastric diseases such as gastritis, ulcers, and gastric cancer. It infects approximately half of the world's population. Risk factors associated with H. pylori infection include socioeconomic status, lifestyle, and diet. Objectives: This study aimed to evaluate the association between eating habits and H. pylori infection in patients from a reference hospital in Central Brazil. Design: This cross-sectional study included 156 patients from 2019 to 2022. Methods: Data were collected using a structured questionnaire on sociodemographic and lifestyle characteristics and a validated food frequency questionnaire. The H. pylori infection status (positive versus negative) was determined using the histopathological method. After grams/day, foods were stratified into tertiles of consumption (low, medium, and high). Simple and multiple binary logistic regression models were used in the analysis of odds ratios (ORs) and their respective 95% confidence intervals (CIs), with a 5% significance level. Results: The prevalence of H. pylori infection was 44.2% (69/156 patients). Infected individuals had a mean age of 49.6 ± 14.6 years; 40.6% were men, 34.8% were aged 60 years or older, 42.0% were unmarried, 7.2% had higher education, 72.5% were non-white, and 30.4% were obese. In the H. pylori-positive group, 55.1% were alcohol drinkers and 42.0% were smokers. The results of multiple analyses showed that the chance of H. pylori infection was higher among male participants (OR = 2.25; CI = 1.09-4.68) and individuals with obesity (OR = 2.68; CI = 1.10-6.51). Participants with moderate consumption of refined grains (bread, cookies, cakes, breakfast cereal) (OR = 2.41; CI = 1.04-5.62) and fruits (OR = 2.53; CI = 1.08-5.94) were more likely to be infected. Conclusion: In this study, male sex, obesity, and the consumption of refined grains and fruits were positively associated with H. pylori infection. Further research is needed to investigate this association and elucidate the underlying mechanisms.

14.
Environ Epidemiol ; 7(3): e251, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-37304339

RESUMO

Organophosphate esters (OPEs) are ubiquitous chemicals, used as flame retardants and plasticizers. OPE usage has increased over time as a substitute for other controlled compounds. This study investigates the impact of prenatal OPE exposure on executive function (EF) in preschoolers. Methods: We selected 340 preschoolers from the Norwegian Mother, Father, and Child Cohort Study. Diphenyl-phosphate (DPhP), di-n-butyl-phosphate (DnBP), bis(2-butoxyethyl) phosphate (BBOEP), and bis(1,3-dichloro-2-propyl) phosphate (BDCIPP) were measured in maternal urine. EF was measured using the Behavior Rating Inventory of Executive Functioning-Preschool (BRIEF-P) and the Stanford-Binet fifth edition (SB-5). EF scores were scaled so a higher score indicated worse performance. We estimated exposure-outcome associations and evaluated modification by child sex using linear regression. Results: Higher DnBP was associated with lower EF scores across multiple rater-based domains. Higher DPhP and BDCIPP were associated with lower SB-5 verbal working memory (ß = 0.49, 95% CI = 0.12, 0.87; ß = 0.53, 95% CI = 0.08, 1.02), and higher BBOEP was associated with lower teacher-rated inhibition (ß = 0.34, 95% CI = 0.01, 0.63). DPhP was associated with lower parent-reported BRIEF-P measures in boys but not girls [inhibition: boys: 0.37 (95% CI = 0.03, 0.93); girls: -0.48 (95% CI = -1.27, 0.19); emotional control: boys: 0.44 (95% CI = -0.13, 1.26); girls: -0.83 (95% CI = -1.73, -0.00); working memory: boys: 0.49 (95% CI = 0.03, 1.08); girls: -0.40 (95% CI = -1.11, 0.36)]. Fewer sex interactions were observed for DnBP, BBOEP, and BDCIPP, with irregular patterns observed across EF domains. Conclusions: We found some evidence prenatal OPE exposure may impact EF in preschoolers and variation in associations by sex.

15.
J. health sci. (Londrina) ; 25(2): 72-77, 20230630.
Artigo em Inglês | LILACS-Express | LILACS | ID: biblio-1510174

RESUMO

Fatigue is a reversible change in biological, physical and psychic functions, resulting from the imbalance of the organism. In patients with head and neck cancer (HNC), fatigue has been cited as one of the most frequent symptoms, especially in individuals with metastasis. It can significantly limit daily activities in order to be considered as a chronic condition, in particular, when associated with painful symptoms. The objective of this studt was to report the occurrence of fatigue and pain in patients with HNC. This was a series of prospective clinical cases describing the clinical history of four patients with HNC submitted to radio chemotherapeutic treatment, users of a public oncology service. To assess the degree of fatigue, the Brief Fatigue Inventory questionnaire was applied at five different moments during the antineoplastic treatment and pain analysis, an analog pain scale was used. The analysis of the questionnaires showed that fatigue was a frequent complaint and intensified with the advance of antineoplastic therapy. Its occurrence was also related to the difficulty performing daily activities. Painful symptomatology has been reported by patients to varying degrees. The occurrence of fatigue and pain in patients with HNC presents variability due to the individual's own experience, reflected by their socioeconomic and cultural context and their personal perception of the illness process.(AU)


A fadiga é uma alteração reversível das funções biológicas, físicas e psíquicas, proveniente do desequilíbrio do organismo. Em pacientes com câncer de cabeça e pescoço (CCP), a fadiga tem sido citada como um dos sintomas mais frequentes, principalmente em indivíduos com metástase. Pode limitar de forma significativa as atividades diárias, de modo a ser considerada uma condição crônica, em especial, quando associada à sintomatologia dolorosa. Este trabalho objetiva relatar a ocorrência de fadiga e dor em pacientes com CCP. Tratou-se de uma série de casos clínicos, de caráter prospectivo, que descreve a história clínica de quatro pacientes com CCP submetidos ao tratamento radioquimioterápico, usuários de um serviço de oncologia público. Para avaliação do grau de fadiga, foi aplicado o questionário Brief Fatigue Inventory em cinco momentos distintos, durante o tratamento antineoplásico e para a análise da dor, foi utilizada uma escala analógica de dor. A análise dos questionários demonstrou que a fadiga foi uma queixa frequente e se intensificou com o avanço da terapia antineoplásica. Sua ocorrência também esteve relacionada à dificuldade de execução de atividades cotidianas. A sintomatologia dolorosa foi relatada pelos pacientes em diferentes graus. A ocorrência de fadiga e dor em pacientes com CCP apresenta variabilidade em razão da experiência vivida pelo próprio indivíduo refletida pelo seu contexto socioeconômico e cultural e a sua percepção pessoal acerca do processo de adoecimento.(AU)

16.
Environ Res ; 225: 115508, 2023 05 15.
Artigo em Inglês | MEDLINE | ID: mdl-36813071

RESUMO

BACKGROUND: Prenatal exposure to phthalates, organophosphate esters, and organophosphorous pesticides have been associated with neurodevelopmental deficits including language ability, however, few studies consider the effect of exposure mixtures and the potential longitudinal detriments over time. OBJECTIVE: This study examines the influence of prenatal exposure to phthalates, organophosphate esters, and organophosphorous pesticides, on children's language ability from toddlerhood to the preschool period. METHODS: This study includes 299 mother-child dyads from Norway in the Norwegian Mother, Father and Child Cohort Study (MoBa). Prenatal exposure to chemicals were assessed at 17 weeks' gestation, and child language skills were assessed at 18 months using the Ages and Stages Questionnaire communication subscale and at preschool age using the Child Development Inventory. We ran two structural equation models to examine the simultaneous influences of chemical exposures on parent-reported and teacher-reported child language ability. RESULTS: Prenatal organophosphorous pesticides were negatively associated with preschool language ability through language ability at 18 months. Additionally, there was a negative association between low molecular weight phthalates and teacher-reported preschool language ability. There was no effect of prenatal organophosphate esters on child language ability at either 18 months or preschool age. CONCLUSIONS: This study adds to the literature on prenatal exposure to chemicals and neurodevelopment and highlights the importance of developmental pathways in early childhood.


Assuntos
Praguicidas , Efeitos Tardios da Exposição Pré-Natal , Gravidez , Feminino , Criança , Humanos , Pré-Escolar , Praguicidas/toxicidade , Efeitos Tardios da Exposição Pré-Natal/induzido quimicamente , Efeitos Tardios da Exposição Pré-Natal/epidemiologia , Estudos de Coortes , Linguagem Infantil , Noruega/epidemiologia , Organofosfatos/toxicidade
17.
Int J Hyg Environ Health ; 248: 114078, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36455478

RESUMO

BACKGROUND: Attention-deficit/hyperactivity-disorder (ADHD) is a leading neurodevelopmental disorder in children worldwide; however, few modifiable risk factors have been identified. Organophosphate esters (OPEs) are ubiquitous chemical compounds that are increasingly prevalent as a replacement for other regulated chemicals. Current research has linked OPEs to neurodevelopmental deficits. The purpose of this study was to assess gestational OPE exposure on clinically-assessed ADHD in children at age 3 years. METHODS: In this nested case-control study within the Norwegian Mother, Father, and Child Cohort study, we evaluated the impact of OPE exposure at 17 weeks' gestation on preschool-age ADHD. Between 2007 and 2011, 260 ADHD cases were identified using the Preschool Age Psychiatric Assessment and compared to a birth-year-stratified control group of 549 children. We categorized bis(2-butoxyethyl) phosphate (BBOEP) and bis(1,3-dichloro-2-propyl) phosphate (BDCIPP) as values < limit of detection (LOD) (BBOEP N = 386, BDCIPP N = 632), ≥LOD but < limit of quantification (LOQ) (BBOEP N = 413; BDCIPP N = 75), or above LOQ (BBOEP N = 70; BDCIPP N = 102). Diphenyl phosphate (DPhP) and di-n-butyl phosphate (DnBP) were categorized as quartiles and also modeled with a log10 linear term. We estimated multivariable adjusted odds ratios (ORs) using logistic regression and examined modification by sex using an augmented product term approach. RESULTS: Mothers in the 3rd DnBP quartile had 1.71 times the odds of having a child with ADHD compared to the 1st quartile (95%CI: 1.13, 2.58); a similar trend was observed for log10 DnBP and ADHD. Mothers with BDCIPP ≥ LOD but < LOQ had 1.39 times the odds of having a child with ADHD compared to those with BDCIPP < LOD (95%CI: 0.83, 2.31). Girls had lower odds of ADHD with increasing BBOEP exposure (log10 OR: 0.55 (95%CI: 0.37, 0.93), however boys had a weakly increased odds (log10 OR: 1.25 (95%CI: 0.74, 2.11) p-interaction = 0.01]. CONCLUSIONS: We found modest increased odds of preschool ADHD with higher DnBP and BDCIPP exposure.


Assuntos
Transtorno do Deficit de Atenção com Hiperatividade , Retardadores de Chama , Masculino , Feminino , Humanos , Pré-Escolar , Criança , Mães , Transtorno do Deficit de Atenção com Hiperatividade/epidemiologia , Estudos de Coortes , Estudos de Casos e Controles , Organofosfatos , Fosfatos , Noruega/epidemiologia , Ésteres , Pai
18.
Front Psychol ; 13: 975086, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36518964

RESUMO

Identification of early promotive and risk factors for social competence is important for fostering children's successful social development; particularly given social competence is essential for children's later academic and psychological well-being. While research suggests that the early parent-child relationship, genetics, and prenatal influences are associated with social competence, there is less research considering how these factors may operate together to shape children's social competence in early childhood. Using a genetically informed sample from the Early Growth and Development Study (N = 561), we examined multiple levels of influence (i.e., genetic, prenatal, parenting, and child characteristics) on children's social competence at 4.5 years old. Results from structural equation models showed adoptive mother overreactivity at 18 months was positively associated with child dysregulation at 27 months, which, in turn, was associated with lower levels of social competence at 4.5 years. Also, child reactivity at 18 months was independently associated with higher levels of adoptive mother overreactivity at 27 months, which, in turn, was associated with lower levels of social competence at 4.5 years. Finally, we found an evocative effect on adoptive fathers' overreactivity at 18 months such that prenatal birth mother distress was negatively associated with adoptive fathers' overreactivity at 18 months. Overall, this study found evidence for genetic influences, and bidirectional associations between parent and child in toddlerhood that are related to lower levels of social competence when children were 4.5 years old. We also found that the prenatal environment was associated with parenting, but not with child behavior directly. This study's ability to simultaneously examine multiple domains of influence helps provide a more comprehensive picture of important mechanisms and developmental periods for children's early social competence.

19.
Artigo em Inglês | MEDLINE | ID: mdl-36554732

RESUMO

Prenatal organophosphorus pesticides (OPs) are ubiquitous and have been linked to adverse neurodevelopmental outcomes. However, few studies have examined prenatal OPs in relation to diagnosed attention-deficit/hyperactivity disorder (ADHD), with only two studies exploring this relationship in a population primarily exposed through diet. In this study, we used a nested case-control study to evaluate prenatal OP exposure and ADHD diagnosis in the Norwegian Mother, Father, and Child Cohort Study (MoBa). For births that occurred between 2003 and 2008, ADHD diagnoses were obtained from linkage of MoBa participants with the Norwegian Patient Registry (N = 297), and a reference population was randomly selected from the eligible population (N = 552). Maternal urine samples were collected at 17 weeks' gestation and molar sums of diethyl phosphates (ΣDEP) and dimethyl phosphates metabolites (ΣDMP) were calculated. Multivariable adjusted logistic regression models were used to estimate the association between prenatal OP metabolite exposure and child ADHD diagnosis. Additionally, multiplicative effect measure modification (EMM) by child sex was assessed. In most cases, mothers in the second and third tertiles of ΣDMP and ΣDEP exposure had slightly lower odds of having a child with ADHD, although confidence intervals were wide and included the null. EMM by child sex was not observed for either ΣDMP or ΣDEP. In summary, we did not find evidence that OPs at 17 weeks' gestation increased the odds of ADHD in this nested case-control study of ADHD in MoBa, a population primarily experiencing dietary exposure.


Assuntos
Transtorno do Deficit de Atenção com Hiperatividade , Praguicidas , Efeitos Tardios da Exposição Pré-Natal , Feminino , Gravidez , Humanos , Criança , Masculino , Mães , Transtorno do Deficit de Atenção com Hiperatividade/induzido quimicamente , Transtorno do Deficit de Atenção com Hiperatividade/epidemiologia , Compostos Organofosforados/toxicidade , Estudos de Coortes , Efeitos Tardios da Exposição Pré-Natal/epidemiologia , Estudos de Casos e Controles , Noruega/epidemiologia , Fosfatos , Pai
20.
Diabetes Res Clin Pract ; 192: 110087, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-36130646

RESUMO

AIM: To model the impact of a 20 % tax on sugar-sweetened beverages (SSBs) on the disease burden of T2DM among Brazilian adults. METHODS: This is an ex-ante risk comparative study. The model applied a 20 % tax on SSB and projected the incidence, prevalence, and mortality of T2DM over a 20-year period (2019 to 2039). Using recent national data on consumption, previously published cross- and own-price elasticities of SSBs and diabetes relative risk we estimated changes on T2DM burden. RESULTS: With a 20 % tax on SSBs, after 10 years, we estimated a reduction of 37,303 new cases of T2DM for men and 56,757 for women; 184,129 prevalent cases for men and 219,236 for women; and 5,386 and 6,075 deaths for men and women, respectively. After 20 years, 8.6 % and 12.4 % new cases of T2DM will have been prevented, 4.0 % and 5.5 % prevalent cases, and 13.7 % and 12.7 % deaths among men and women, respectively. CONCLUSIONS: SSB taxes have the potential to reduce the burden of and deaths attributable to T2DM. Our results show that a fiscal policy may significantly impact strategic plans to tackle noncommunicable diseases.


Assuntos
Diabetes Mellitus Tipo 2 , Bebidas Adoçadas com Açúcar , Adulto , Masculino , Feminino , Humanos , Bebidas Adoçadas com Açúcar/efeitos adversos , Diabetes Mellitus Tipo 2/epidemiologia , Diabetes Mellitus Tipo 2/prevenção & controle , Brasil/epidemiologia , Bebidas/efeitos adversos , Impostos
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