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Although the presence of nitro groups in chemicals can be recognized as structural alerts for mutagenicity and carcinogenicity, nitroaromatic compounds have attracted considerable interest as a class of agents that can serve as source of potential new anticancer agents. In the present study, the in vitro cytotoxicity, genotoxicity, and mutagenicity of three synthetic ortho-nitrobenzyl derivatives (named ON-1, ON-2 and ON-3) were evaluated by employing human breast and ovarian cancer cell lines. A series of biological assays was carried out with and without metabolic activation. Complementarily, computational predictions of the pharmacokinetic properties and druglikeness of the compounds were performed in the Swiss ADME platform. The MTT assay showed that the compounds selectively affected selectively the cell viability of cancer cells in comparison with a nontumoral cell line. Additionally, the metabolic activation enhanced cytotoxicity, and the compounds affected cell survival, as demonstrated by the clonogenic assay. The comet assay, the cytokinesis-block micronucleus assay, and the immunofluorescence of the γ-H2AX foci formation assay have that the compounds caused chromosomal damage to the cancer cells, with and without metabolic activation. The results obtained in the present study showed that the compounds assessed were genotoxic and mutagenic, inducing double-strand breaks in the DNA structure. The high selectivity indices observed for the compounds ON-2 and ON-3, especially after metabolic activation with the S9 fraction, must be highlighted. These experimental biological results, as well as the theoretical properties predicted for the compounds have shown that they are promising anticancer candidates to be exploited in additional studies.
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Ativação Metabólica , Antineoplásicos , Sobrevivência Celular , Dano ao DNA , Humanos , Sobrevivência Celular/efeitos dos fármacos , Antineoplásicos/toxicidade , Antineoplásicos/farmacologia , Antineoplásicos/química , Dano ao DNA/efeitos dos fármacos , Linhagem Celular Tumoral , Testes para Micronúcleos , Mutagênicos/toxicidade , Ensaio Cometa , Testes de Mutagenicidade , Feminino , Nitrobenzenos/toxicidade , Nitrobenzenos/química , Neoplasias da Mama/patologia , Neoplasias da Mama/tratamento farmacológico , Neoplasias Ovarianas/patologia , Neoplasias Ovarianas/tratamento farmacológico , Relação Dose-Resposta a DrogaRESUMO
We present our results on the synthesis and preliminary in silico and in vitro studies of the toxicology and antioxidant properties of selenylated analogs of Tacrine. Initially, we synthesized 2-aminobenzonitriles containing an organic selenium moiety, resulting in sixteen compounds with various substituents linked to the portion derived from diorganyl diselenide. These compounds were then used as substrates in reactions with cyclic ketones, in the presence of 1.4 equivalents of trifluoroboroetherate as a Lewis acid, to synthesize selenylated analogs of Tacrine with yields ranging from 20% to 87%. In silico studies explored computational parameters related to antioxidant activity and hepatotoxicity. In vitro studies elucidated the antioxidant effects of Tacrine and its selenium hybrid (TSe) in neutralizing ABTS radicals, scavenging DPPH radicals, and reducing iron ions. Additionally, the acute oral toxicity of one synthesized compound was evaluated.
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Several therapies have been developed to reduce cognitive decline associated with aging. Aquatic exercises, which are widely used to enhance functional capacity, may play a role in stimulating cognitive functions. This study investigated the effects of a 3-month aquatic exercise program on cognitive functions in community-dwelling older adults. In this prospective, single-blinded, controlled clinical trial, 31 participants were allocated to either the experimental (aquatic exercises) or control (no-exercise) group. The intervention program consisted of exercises conducted twice a week in a 1.2 m deep indoor pool. The main outcome measures were cognitive functions, assessed using Raven's Progressive Matrices test and the Wisconsin Card Sorting Test. A repeated-measures analysis of variance was used to assess the impact of the exercise program. The effect sizes (η2p) were reported when a level of significance was achieved (p < 0.05). Compared with the control group, the participants who underwent aquatic exercises showed positive outcomes in Raven's Progressive Matrices test (p = 0.046; η2p = 0.131) and the Wisconsin Card Sorting Test (p = 0.001, η2p = 0.589). Complementary analyses of the Wisconsin Card Sorting Test indicated that the benefits of the aquatic exercise were observed in terms of the number of trials (p = 0.001, η2p = 0.478), number of errors (p = 0.001, η2p = 0.458), and number of non-perseverative errors (p = 0.001, η2p = 0.302). The results indicate that a period of three months of aquatic exercise was beneficial for stimulating specific aspects of the cognitive function of community-dwelling older individuals. Aquatic exercise should be prescribed to this population.
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This study aimed to compare the smile's attractiveness in patients submitted to the treatment of gummy smiles with botulinum toxin or maxillary impaction surgery. The retrospective sample comprised 26 patients divided into two groups: Group 1 (BTX): 13 patients (12 females and 1 male) with a mean age of 28.06 years (s.d. = 6.09) and mean gingival exposure during smile of 5.18 mm (s.d. = 1.51) treated with botulinum toxin; Group 2 (SURGICAL): 13 patients (9 females and 4 males) with a mean age of 30.59 years (s.d. = 5.72) and mean gingival exposure during smile of 5.21 mm (s.d. = 1.55) treated with orthognathic maxillary impaction surgery. The group of evaluators comprised 317 participants, divided into 143 orthodontists (85 females and 58 males) with a mean age of 41.40 (s.d. = 9.30); 62 dentists (47 female and 15 male) with a mean age of 35.44 (s.d. = 10.44), and 112 lay people (74 female and 38 male) with a mean age of 46, 91 (s.d. = 10.11) in a questionnaire on Google Forms. Without knowing the therapy used, the evaluators assigned scores to the photographs of the posed smile taken before (T1) and after (T2) treatment. Intergroup comparison of smile attractiveness was performed using the t-independent, one-way ANOVA, and Tukey tests. There was a significant improvement in smile attractiveness with treatment in both groups; however, the improvement was significantly better in the surgical group than in the BTX group. Orthodontists rated smile attractiveness significantly higher than dentists and laypersons for the final phase of the BTX and surgical groups. There was a significant improvement in the smile attractiveness with botulinum toxin application and orthodontic-surgical treatment. However, orthognathic surgery promoted a greater improvement in smile attractiveness than the application of botulinum toxin.
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OBJECTIVE: To assess the social, metabolic, and lifestyle determinants of consumption of fruits, vegetables, and greens (FVG) and ultra-processed food (ULT) in adults from Pernambuco. METHODS: Cross-sectional and analytical study, conducted in 2015/2016. In addition to sociodemographic variables, the determinants of lifestyle were level of physical activity, alcohol consumption, tobacco use, and metabolic variables were self-reported hypertension, blood glucose, and Body Mass Index (BMI). Consumption was measured by the Food Frequency Questionnaire, then created the Frequency of Consumption Index (SFI) of the mean intake of ULT and FVG foods. The indices of FVG and ULT consumption were transformed into quartiles and these variables were included in the multinomial logistic regression, considering their determinants when p<0.05. RESULTS: The sample was representative of the state, with 1,067 people being interviewed, whose intake of ULT was higher than that of FVG in the lowest and highest quartile of the consumption index. Consumption of fruit and vegetables was higher in higher consumption of alcoholic beverages (p=0.031) and BMI>25 kg/m2 (p=0.047); and lower in the lowest income (p=0.001). ULT intake was higher in young adults (p=0.005), lower income (p=0.044), and controlled blood glucose (p=0.021). Rural areas were 52% less exposed to medium-high ULT consumption (p<0.006). CONCLUSION: Higher rate of ULT consumption in relation to fresh foods, with income as a common determinant, inversely associated with ULT intake and directly related to FVG, which demands structuring policies.
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Alimento Processado , Estilo de Vida , Fatores Socioeconômicos , Adolescente , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem , Consumo de Bebidas Alcoólicas/epidemiologia , Índice de Massa Corporal , Brasil , Estudos Transversais , Dieta/estatística & dados numéricos , Comportamento Alimentar , Frutas , Fatores Sociodemográficos , VerdurasRESUMO
INTRODUCTION: Benznidazole, the drug of choice for treating Chagas Disease (CD), has significant limitations, such as poor cure efficacy, mainly in the chronic phase of CD, association with side effects, and parasite resistance. Understanding parasite resistance to benznidazole is crucial for developing new drugs to treat CD. AREAS COVERED: Here, the authors review the current understanding of the molecular basis of benznidazole resistance. Furthermore, they discuss the state-of-the-art methods and critical outcomes employed to evaluate the efficacy of potential drugs against T. cruzi, aiming to select better compounds likely to succeed in the clinic. Finally, the authors describe the different strategies employed to overcome resistance to benznidazole and find effective new treatments for CD. EXPERT OPINION: Resistance to benznidazole is a complex phenomenon that occurs naturally among T. cruzi strains. The combination of compounds that inhibit different metabolic pathways of the parasite is an important strategy for developing a new chemotherapeutic protocol.
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Doença de Chagas , Descoberta de Drogas , Resistência a Medicamentos , Nitroimidazóis , Tripanossomicidas , Trypanosoma cruzi , Trypanosoma cruzi/efeitos dos fármacos , Nitroimidazóis/farmacologia , Doença de Chagas/tratamento farmacológico , Doença de Chagas/parasitologia , Tripanossomicidas/farmacologia , Humanos , Animais , Descoberta de Drogas/métodos , Desenvolvimento de MedicamentosRESUMO
The care of adolescents in reclusion has been a field of work for occupational therapists in different parts of the world. The objective of this study was to describe and analyze Brazilian occupational therapists' practices with adolescents in reclusion. Research conducted in Brazil, identifying 56 professionals, invited to answer a questionnaire (n = 43); participate in discussion groups (n = 9); and interview (n = 4). Professionals reported different visions that guide their practices, including the identification of individual skills and the profession's possibilities for social action. Occupational therapists have specificities to work in these institutions, highlighting the possibilities of acting with a focus on social change. Practices in occupational therapy can lead to social change if focused on social issues. Social occupational therapy offers theoretical and methodological elements that inform the profession. Reflections on the practice carried out, according to a critical perspective, enable a performance in occupational therapy that intends social change.
OBJECTIVE: The objective was to describe and analyze the practice of occupational therapists in custodial units of the Brazilian juvenile justice system. METHODOLOGY: Mapping and identification of occupational therapists in institutions of juvenile incarceration; questionnaire; workshops; semi-structured interviews; and synthesis meeting. RESULTS AND DISCUSSION: Forty-three professionals with diverse practices participated in this study. The collected data in the different stages of the research were analyzed based on social occupational therapy. CONCLUSION: Occupational therapy practices can lead to social change if focused on social issues. Social occupational therapy offers theoretical and methodological elements for that.
Occupational Therapy and Imprisoned Adolescents: An Analysis of Professional PracticesIntroduction: In Brazil, the number of adolescents convicted of infractions is increasing. Judicial sanctions may be imposed on this population, including imprisonment. There are occupational therapists working with these adolescents, but their practices are little recorded and debated.
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OBJECTIVE: Safe, effective, and biocompatible minimally invasive procedures with the potential to stimulate collagen production have been made to recover dermal thickness and skin quality. The main of this animal model experiment was to observe the effect of poly-L-lactic acid (PLLA) and polydioxanone (PDO) biostimulators in collagen I and III after hypodermal injection. METHODOLOGY: Sixteen adult female rats (Wistar) were randomized into four groups and had dorsal treatment with: G1: hypodermic subcision (HS) only; G2: HS and PLLA hypodermic injection (HI), G3: HS and PDO HI; G4: Control, with no treatment. RESULTS: In histochemical, it was observed hypodermal and dermal tissue in more organized thickness in G3 and in G4 when compared to G1 and G2. There was few difference in G1 compared to G4. The tissue of G2 showed irregularities in the arrangement of collagen fibers, less defined structure and lower distribution of type I collagen compared to the other groups. There is a greater tendency for the proportions of type III collagen among tissues treated with both biostimulators (G2 and G3). PLLA and PDO had relatively similar percentages of collagen when compared to G4. The amount of type I collagen was higher in tissues treated with subcision, while type III collagen was higher in tissues treated with both biostimulators. CONCLUSION: G3 showed better performance in collagen production, although small, when compared with G2.
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Colágeno Tipo I , Polidioxanona , Poliésteres , Ratos , Feminino , Animais , Polidioxanona/farmacologia , Colágeno Tipo III , Ratos Wistar , ColágenoRESUMO
BACKGROUND: The self-administered Kidney AlloTransplant Immunosuppressive Therapy Adherence (KATITA-25) questionnaire is a multidimensional scale for use in the pretransplant setting that evaluates the predisposition to nonadherence of patients who are candidates to kidney transplant. The scale has shown adequate internal consistency and test-retest reliability. This study presents the results of an external validation study of the KATITA-25 scale. METHODS: Patients >18 y old scheduled for kidney transplant were included in this multicenter study. The KATITA-25 scale was administered before surgery and then at 3-mo posttransplantation for evaluation of scale sensitivity to change. At this time, 2 validated medication adherence scales were applied for assessment of concurrent validity. For evaluation of predictive validity, nonadherence to immunosuppressive medication was assessed at 6 and 12 mo after transplantation by 3 independent methods: patient self-report of nonadherence using the Morisky-Green-Levine Medication Assessment Questionnaire scale, serum trough levels of immunosuppressants, and pharmacy refills. RESULTS: Three twenty-two patients were available for evaluation of concurrent validity and 311 patients of predictive validity. After kidney transplant, the median KATITA-25 score decreased from 20 to 8 ( P â <â 0.001), demonstrating scale sensitivity to change, and the KATITA-25 score showed correlation with the Basel Assessment of Adherence to Immunosuppressive Medication Scale score (Spearman's ρ 0.18, P â =â 0.002) and the Cuestionario para la Evaluación de la Adhesión al Tratamiento Antiretroviral scores (ρ -0.17, P â =â 0.002), confirming concurrent validity. The nonadherence rate was 57.6%. The scale predictive validity was demonstrated by the area under the receiver operating characteristics curve (0.68), sensitivity (59.8%), specificity (68.2%), and positive predictive value (71.8%). CONCLUSIONS: This external validation study of KATITA-25 scale provided evidence of sensitivity to change, and structural, criterion, and predictive validity.
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Imunossupressores , Transplante de Rim , Adesão à Medicação , Humanos , Imunossupressores/uso terapêutico , Masculino , Feminino , Pessoa de Meia-Idade , Adesão à Medicação/estatística & dados numéricos , Reprodutibilidade dos Testes , Adulto , Inquéritos e Questionários/estatística & dados numéricos , Idoso , Autorrelato , Resultado do Tratamento , Rejeição de Enxerto/prevenção & controle , Rejeição de Enxerto/imunologia , Fatores de TempoRESUMO
The application of computer-aided drug discovery (CADD) approaches has enabled the discovery of new antimicrobial therapeutic agents in the past. The high prevalence of methicillin-resistantStaphylococcus aureus(MRSA) strains promoted this pathogen to a high-priority pathogen for drug development. In this sense, modern CADD techniques can be valuable tools for the search for new antimicrobial agents. We employed a combination of a series of machine learning (ML) techniques to select and evaluate potential compounds with antibacterial activity against methicillin-susceptible S. aureus (MSSA) and MRSA strains. In the present study, we describe the antibacterial activity of six compounds against MSSA and MRSA reference (American Type Culture Collection (ATCC)) strains as well as two clinical strains of MRSA. These compounds showed minimal inhibitory concentrations (MIC) in the range from 12.5 to 200 µM against the different bacterial strains evaluated. Our results constitute relevant proven ML-workflow models to distinctively screen for novel MRSA antibiotics.
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Antibacterianos , Staphylococcus aureus Resistente à Meticilina , Antibacterianos/farmacologia , Staphylococcus aureus , Meticilina/farmacologia , Testes de Sensibilidade MicrobianaRESUMO
This study aimed to compare AFM1 occurrence in different cheese types produced by organic and conventional systems; and to evaluate the risk of food exposure to AFM1. A total of 176 commercial cheeses of 17 types were analyzed, 84 of organic and 92 of conventional production. Determination of AFM1 was performed by high- performance liquid chromatography (HPLC), being detected in 30.5% of samples, with 4.8% of organic cheese samples presenting quantifiable AFM1 values between 0.88 and 1.50 µg/kg. On the other hand, 4.3% of conventional cheese samples with values between 0.79 and 6.70 µg/kg. Two conventional cheese samples were above the limit of AFM1 allowed for cheeses by the Brazilian legislation. No statistical difference were found between organic and conventional cheeses regarding the occurrence (p = 0.1780) and concentration of AFM1 (p = 0.1810), according to the Chi-square and the T test, respectively. Estimated daily intake (EDI) and hazard index (HI) of dietary exposure to AFM1 were 0.26 ng/kg/day and 1.28 ng/kg/day, respectively, for conventional cheese samples, and 0.09 ng/kg/day and 0.47 ng/kg/day for organic samples, with no statistical difference for EDI (p = 0.1729) and HI (p = 0.1802) between the two production systems. Comparison between several cheese types from conventional and organic systems indicated that AFM1 is an obstacle to dairy production. Control and prevention of AFM1 contamination, as well as detoxification methods in the final products, are necessary. In the case of organic products, additional research is needed in order to determine which control and detoxification methods should be allowed in this production system.
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Aflatoxina M1 , Queijo , Contaminação de Alimentos , Aflatoxina M1/análise , Contaminação de Alimentos/análise , Humanos , Exposição Dietética , Brasil , Cromatografia Líquida de Alta PressãoRESUMO
The aim of this study was to describe epidemiological characteristics and perform SARS-CoV-2 genomic surveillance in the southeastern region of São Paulo State. During the first months of 2022, we compared weekly SARS-CoV-2 infection prevalence considering age, Ct value, and variants' lineages. An increase in the number of SARS-CoV-2-positive cases until the fourth epidemiological week of 2022 was observed. From the fourth epidemiological week onwards, the number of tests for SARS-CoV-2 diagnosis began to decrease, but the number of positive samples for SARS-CoV-2 remained high, reaching its most expressive level with a rate of 60% of infected individual cases. In this period, we observed a progressive increase in SARS-CoV-2 infection within the 0-10 age group throughout the epidemiological weeks, from 2.8% in the first epidemiological week to 9.2% in the eighth epidemiological week of 2022. We further observed significantly higher Ct values within younger patient samples compared to other older age groups. According to lineage assignment, SARS-CoV-2 (BA.1) was the most prevalent (74.5%) in the younger group, followed by BA.1.1 (23%), BA.2 (1.7%), and Delta (1%). Phylogenetic analysis showed that BA.2 sequences clustered together, indicating sustained transmission of this Omicron VOC sub-lineage by that time. Our results suggest the initial dissemination steps of the Omicron's sub-linage BA.2 into the younger group, due to specific genomic features of the detected sequences. These data provide interesting results related to the spread, emergence, and evolution of the Omicron variant in the southeast Brazilian population.
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RN104 (2-[2-(cyclohexylmethylene)hydrazinyl)]-4-phenylthiazole) is a thiazolylhydrazone derivative with prominent antifungal activity. This work aimed to develop a self-emulsifying drug delivery system (SEDDS) loaded with RN104 to improve its biopharmaceutical properties and enhance its oral bioavailability. Medium chain triglycerides, sorbitan monooleate, and polysorbate 80 were selected as components for the SEDDS formulation based on solubility determination and a pseudo-ternary phase diagram. The formulation was optimized using the central composite design in response surface methodology. The optimized condition consisted of medium chain triglycerides, sorbitan monooleate, and polysorbate 80 in a mass ratio of 65.5:23.0:11.5, achieving maximum drug loading (10 mg/mL) and minimum particle size (118.4 ± 0.7 nm). The developed RN104-SEDDS was fully characterized using dynamic light scattering, in vitro release studies, stability assessments, polarized light microscopy, and transmission electron microscopy. In vivo pharmacokinetic studies in mice demonstrated that RN104-SEDDS significantly improved oral bioavailability compared to free RN104 (the relative bioavailability was 2133 %). These results clearly indicated the successful application of SEDDS to improve the pharmacokinetic profile and to enhance the oral bioavailability of RN104, substantiating its potential as a promising antifungal drug candidate.
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Antifúngicos , Polissorbatos , Camundongos , Animais , Emulsões/farmacocinética , Disponibilidade Biológica , Solubilidade , Sistemas de Liberação de Medicamentos/métodos , Triglicerídeos , Administração OralAssuntos
Vírus da Dengue , Dengue , Humanos , Brasil/epidemiologia , Vírus da Dengue/genética , Dengue/epidemiologia , GenótipoRESUMO
OBJECTIVE: To compare the anterior crowding correction after sequential use of the first 5 aligners between two aligner exchange protocols (7 and 14 days) in mature adult patients. MATERIALS AND METHODS: Thirty-six patients over 35 years who received orthodontic treatment with Invisalign® were randomly allocated to two different aligner replacement sequence protocols: Group 1: exchange every 7 days (n = 18); and Group 2: exchange every 14 days (n = 18). All patients were scanned with iTero Element 5D® (Align Technology) in two treatment times: at pre-treatment (T1) and after using the first five aligners (T2). Little's Irregularity Index (LII) and arch widths were evaluated with OrthoCAD software. Intra and intergroup comparisons were performed with the dependent and independent t-tests. The results were considered significant for P < .05. RESULTS: Thirty-five patients completed the study. Both groups' maxillary and mandibular Irregularity Indexesi were significantly lower at T2. There was no significant difference in inter-canine, inter-premolar, and intermolar distances. G2 (14 days) presented a greater decrease in mandibular irregularity than G1 (7 days). CONCLUSION: Both exchange protocols (7 and 14 days) effectively correct anterior crowding in the initial phase of orthodontic treatment with aligners in mature adult patients. However, the 14-day exchange protocol provided a greater correction in mandibular anterior crowding in the evaluated period than the 7-day exchange protocol.
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Má Oclusão , Técnicas de Movimentação Dentária , Humanos , Adulto , Masculino , Feminino , Má Oclusão/terapia , Técnicas de Movimentação Dentária/instrumentação , Técnicas de Movimentação Dentária/métodos , Desenho de Aparelho Ortodôntico , Resultado do Tratamento , Fatores de Tempo , Aparelhos Ortodônticos Removíveis , Pessoa de Meia-IdadeRESUMO
INTRODUCTION: American Tegumentary Leishmaniasis (ATL) treatment is based on pentavalent antimonials (Sb5+), but these drugs have been associated to several adverse effects. Hearing loss and tinnitus during treatment with meglumine antimoniate (MA) have already been reported. This study aimed to describe the usefulness of self-reporting of hearing loss and tinnitus in diagnosing MA-induced ototoxicity. METHODS: A prospective longitudinal study was conducted with 102 patients with parasitological diagnosis of ATL, treated with different MA schemes. The presence of clinical auditory toxicity was defined as the emergence or worsening of self-reporting hearing loss and/or tinnitus during monitoring. Measures of sensitivity, specificity, and the positive and negative predictive value of the patient's self-reporting of hearing loss and tinnitus in relation to the result of the audiometric test (considered the gold standard) were calculated. RESULTS: The age of the evaluated patients ranged from 15 to 81 years, with a median of 41 years, and most were male (73.5%). Seventy-five patients (73.5%) had cutaneous leishmaniasis and 27 (26.5%) mucosal leishmaniasis. Eighty-six patients (84.3%) received intramuscular (IM) treatment and 16 (15.7%) were treated with intralesional MA. During treatment, 18 (17,6%) had tinnitus and 7 (6,9%) had complaint of hearing loss. 53 (52%) patients had cochlear toxicity confirmed by tone threshold audiometry and high frequency audiometry, from which 60% received a dose of 20 mg Sb5+/kg/day (p = 0.015) and 96.2% were treated with IM MA (p = 0.001). Tinnitus has greater specificity and positive predictive value than hearing loss, with a low number of false positives, but with a high false negative value. CONCLUSION: Although the large number of false negatives suggests that self-report of hearing loss or tinnitus cannot be considered a good screening test for referring the patient to an audiometry, the low number of false positives suggests the need to value the patient's complaint for referral. Otherwise, this study reinforces the importance of audiological monitoring during treatment with MA, especially in those patients with self-reporting of hearing loss or tinnitus when treated with 20 mg Sb5+/kg/day via IM.
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Antiprotozoários , Surdez , Perda Auditiva , Leishmaniose Cutânea , Compostos Organometálicos , Ototoxicidade , Zumbido , Humanos , Masculino , Adolescente , Adulto Jovem , Adulto , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Feminino , Antimoniato de Meglumina/efeitos adversos , Zumbido/induzido quimicamente , Zumbido/diagnóstico , Zumbido/tratamento farmacológico , Meglumina/efeitos adversos , Antiprotozoários/uso terapêutico , Estudos Longitudinais , Estudos Prospectivos , Compostos Organometálicos/efeitos adversos , Leishmaniose Cutânea/diagnóstico , Leishmaniose Cutânea/tratamento farmacológico , Perda Auditiva/induzido quimicamente , Perda Auditiva/diagnósticoRESUMO
Cannabidiol (CBD) is a substance that exerts several therapeutic actions, including analgesia. CBD is generally administered orally, but its poor water solubility and metabolism impair its bioavailability. Thus, the development of molecules with better pharmacokinetic profile from cannabidiol becomes an interesting strategy for the design of novel analgesic drugs for the relief of painful conditions that are difficult to manage clinically, such as neuropathic pain. In the present study, an unprecedented analogue of CBD (1) was synthesized and some of its physicochemical properties were evaluated inâ silico as well as its stability in an acid medium. Additionally, its effect was investigated in a model of neuropathic pain induced by the chemotherapy drug paclitaxel in mice, in comparison with cannabidiol itself. Cannabidiol (20â mg/kg), pregabalin (30â mg/kg), or analogue 1 (5, 10, and 20â mg/kg), administered on the 14th day after the first administration of paclitaxel, attenuated the mechanical allodynia of the sensitized animals. The antinociceptive activity of analogue 1 was attenuated by previous administration of a cannabinoid CB1 receptor antagonist, AM 251, which indicates that its mechanism of action is related to the activation of CB1 receptors. In conclusion, the CBD analogue 1 developed in this study shows great potential to be used in the treatment of neuropathic pain.
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Canabidiol , Neuralgia , Camundongos , Animais , Canabidiol/efeitos adversos , Modelos Animais de Doenças , Neuralgia/tratamento farmacológico , Neuralgia/induzido quimicamente , Paclitaxel/farmacologia , Analgésicos/farmacologia , Analgésicos/uso terapêuticoRESUMO
OBJECTIVE: To analyze clinical and sociodemographic factors associated with the health-related quality of life of children and adolescents with type 1 Diabetes Mellitus. METHOD: A quantitative, cross-sectional and analytical study, developed in a municipality in northeastern Brazil, between March and September 2021, with 81 children/adolescents with type 1 Diabetes Mellitus and their guardians/caregivers. A questionnaire containing sociodemographic and clinical variables and two quality of life instruments were used. Descriptive and inferential analysis was carried out. RESULTS: Adolescents whose parents had a family income greater than a minimum wage had a lower prevalence of impaired quality of life when compared to those with a lower income. Adolescents with time since diagnosis of less than four years had a satisfactory quality of life, and children aged 8 to 12 years who self-administered insulin had a lower prevalence of high quality of life compared to those who did not. CONCLUSION: Adolescents with a family income of less than a minimum wage, diagnosis time of more than four years and children aged 8-12 who self-administer insulin need greater professional support to have a better quality of life.
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Diabetes Mellitus Tipo 1 , Criança , Adolescente , Humanos , Qualidade de Vida , Fatores Sociodemográficos , Estudos Transversais , InsulinaRESUMO
OBJECTIVE: The aim of this study was to investigate the frequency of breakfast consumption and estimate its associations with the consumption of food at different degrees of industrial processing and with overweight indicators in Brazilian adolescents. METHODS: This cross-sectional study involved a probabilistic sample of 14- to 19-y-old adolescents enrolled in 29 public schools in the municipality of Juiz de Fora, MG, Southeast Brazil (n = 805). The frequency of breakfast consumption was evaluated via a questionnaire (classified into "do not consume", "sometimes consume", and "regularly consume"). The evaluation of food consumption involved two 24-h dietary recalls, the items of which were analyzed according to the NOVA classification system. Overweight indicators (waist circumference, body mass index for age (BMI-for-age), and body fat percentage) were evaluated according to a standard protocol. Linear regression models were performed, first without and then with adjustments for sociodemographic characteristics. RESULTS: We found that 20% of adolescents skipped breakfast, and â¼46% of the caloric intake came from ultra-processed foods. Breakfast omission was associated with a mean increase of 3.02% (95% confidence interval [CI], 0.52-5.53) in energy intake from ultra-processed foods, in addition to a mean increase of 0.28 z-score (95% CI, 0.05- 0.52) of BMI-for-age and of 1.64% (95% CI, 0.21-3.08) in body fat. CONCLUSIONS: We verified that the omission of breakfast was associated with higher consumption of ultra-processed foods, as well as a higher BMI-for-age and higher percentage of body fat, reinforcing the importance of actions to encourage the consumption of this meal and the adoption of healthy eating practices in adolescents.
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Desjejum , Sobrepeso , Humanos , Adolescente , Sobrepeso/epidemiologia , Brasil/epidemiologia , Estudos Transversais , Comportamento Alimentar , Dieta , Ingestão de Energia , Fast FoodsRESUMO
ABSTRACT Objective: To assess the social, metabolic, and lifestyle determinants of consumption of fruits, vegetables, and greens (FVG) and ultra-processed food (ULT) in adults from Pernambuco. Methods: Cross-sectional and analytical study, conducted in 2015/2016. In addition to sociodemographic variables, the determinants of lifestyle were level of physical activity, alcohol consumption, tobacco use, and metabolic variables were self-reported hypertension, blood glucose, and Body Mass Index (BMI). Consumption was measured by the Food Frequency Questionnaire, then created the Frequency of Consumption Index (SFI) of the mean intake of ULT and FVG foods. The indices of FVG and ULT consumption were transformed into quartiles and these variables were included in the multinomial logistic regression, considering their determinants when p<0.05. Results: The sample was representative of the state, with 1,067 people being interviewed, whose intake of ULT was higher than that of FVG in the lowest and highest quartile of the consumption index. Consumption of fruit and vegetables was higher in higher consumption of alcoholic beverages (p=0.031) and BMI>25 kg/m2 (p=0.047); and lower in the lowest income (p=0.001). ULT intake was higher in young adults (p=0.005), lower income (p=0.044), and controlled blood glucose (p=0.021). Rural areas were 52% less exposed to medium-high ULT consumption (p<0.006). Conclusion: Higher rate of ULT consumption in relation to fresh foods, with income as a common determinant, inversely associated with ULT intake and directly related to FVG, which demands structuring policies.
RESUMO Objetivo: Avaliar os determinantes sociais, metabólicos e de estilo de vida do consumo de frutas, legumes e verduras (FLV) e ultraprocessados (ULT) em adultos de Pernambuco. Métodos: Estudo transversal e analítico, realizado em 2015/2016. Além de variáveis sociodemográficas, os determinantes do estilo de vida foram nível de atividade física, doses de bebida alcoólica e uso de tabaco e os metabólicos foram hipertensão autorreferida, glicemia e Índice de Massa Corporal (IMC). O consumo foi mensurado por questionário de frequência alimentar, e, em seguida, criou-se Índice da Frequência de Consumo (IFC) da média de ingestão dos alimentos ULT e FVL. Os índices de consumo de FLV e ULT foram transformados em quartis e essas variáveis incluídas na regressão logística multinomial, considerando seus determinantes quando p<0,05. Resultados: A amostra foi representativa do estado, sendo entrevistadas 1.067 pessoas, cuja ingestão de ULT foi superior à de FVL no menor e no maior quartil do índice de consumo. O consumo de FLV foi superior no maior consumo de bebida alcoólica (p=0,031) e IMC>25 kg/m2 (p=0,047); e inferior na menor renda (p=0,001). O consumo de ULT foi maior em adultos jovens (p=0,005), menor renda (p=0,044) e glicemia controlada (p=0,021). A área rural estava 52% menos exposta ao consumo médio-alto de ULT (p<0,006). Conclusão: Maior índice de consumo de ULT em relação aos alimentos in natura, tendo a renda como um determinante comum, inversamente associada à ingestão de ULT e diretamente relacionada a FVL, o que demanda políticas estruturantes.