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1.
Adv Rheumatol ; 64(1): 52, 2024 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-38987832

RESUMO

BACKGROUND: Systemic sclerosis (SSc) is a rare chronic autoimmune disease with heterogeneous manifestations. In the last decade, several clinical trials have been conducted to evaluate new treatment options for SSc. The purpose of this work is to update the recommendations of the Brazilian Society of Rheumatology in light of the new evidence available for the pharmacological management of SSc. METHODS: A systematic review including randomized clinical trials (RCTs) for predefined questions that were elaborated according to the Patient/Population, Intervention, Comparison, and Outcomes (PICO) strategy was conducted. The rating of the available evidence was performed according to the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology. To become a recommendation, at least 75% agreement of the voting panel was needed. RESULTS: Six recommendations were elaborated regarding the pharmacological treatment of Raynaud's phenomenon, the treatment (healing) and prevention of digital ulcers, skin involvement, interstitial lung disease (ILD) and gastrointestinal involvement in SSc patients based on results available from RCTs. New drugs, such as rituximab, were included as therapeutic options for skin involvement, and rituximab, tocilizumab and nintedanib were included as therapeutic options for ILD. Recommendations for the pharmacological treatment of scleroderma renal crisis and musculoskeletal involvement were elaborated based on the expert opinion of the voting panel, as no placebo-controlled RCTs were found. CONCLUSION: These guidelines updated and incorporated new treatment options for the management of SSc based on evidence from the literature and expert opinion regarding SSc, providing support for decision-making in clinical practice.


Assuntos
Doença de Raynaud , Reumatologia , Escleroderma Sistêmico , Escleroderma Sistêmico/complicações , Escleroderma Sistêmico/tratamento farmacológico , Humanos , Brasil , Reumatologia/normas , Doença de Raynaud/tratamento farmacológico , Sociedades Médicas , Doenças Pulmonares Intersticiais/tratamento farmacológico , Anticorpos Monoclonais Humanizados/uso terapêutico , Rituximab/uso terapêutico , Ensaios Clínicos Controlados Aleatórios como Assunto , Úlcera Cutânea/etiologia , Antirreumáticos/uso terapêutico
2.
J Biol Chem ; 300(8): 107495, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38925327

RESUMO

Transthyretin (TTR) is an homotetrameric protein involved in the transport of thyroxine. More than 150 different mutations have been described in the TTR gene, several of them associated with familial amyloid cardiomyopathy. Recently, our group described a new variant of TTR in Brazil, namely A39D-TTR, which causes a severe cardiac condition. Position 39 is in the AB loop, a region of the protein that is located within the thyroxine-binding channels and is involved in tetramer formation. In the present study, we solved the structure and characterize the thermodynamic stability of this new variant of TTR using urea and high hydrostatic pressure. Interestingly, during the process of purification, A39D-TTR turned out to be a dimer and not a tetramer, a variation that might be explained by the close contact of the four aspartic acids at position 39, where they face each other inside the thyroxine channel. In the presence of subdenaturing concentrations of urea, bis-ANS binding and dynamic light scattering revealed A39D-TTR in the form of a molten-globule dimer. Co-expression of A39D and WT isoforms in the same bacterial cell did not produce heterodimers or heterotetramers, suggesting that somehow a negative charge at the AB loop precludes tetramer formation. A39D-TTR proved to be highly amyloidogenic, even at mildly acidic pH values where WT-TTR does not aggregate. Interestingly, despite being a dimer, aggregation of A39D-TTR was inhibited by diclofenac, which binds to the thyroxine channel in the tetramer, suggesting the existence of other pockets in A39D-TTR able to accommodate this molecule.


Assuntos
Cardiomiopatias , Pré-Albumina , Multimerização Proteica , Termodinâmica , Pré-Albumina/genética , Pré-Albumina/química , Pré-Albumina/metabolismo , Humanos , Cardiomiopatias/metabolismo , Cardiomiopatias/genética , Tiroxina/metabolismo , Tiroxina/química , Mutação de Sentido Incorreto , Amiloide/metabolismo , Amiloide/química , Amiloide/genética , Substituição de Aminoácidos , Ureia/química , Ureia/metabolismo
3.
J Neurosurg ; 141(4): 887-894, 2024 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-38728757

RESUMO

OBJECTIVE: Spin is characterized as a misinterpretation of results that, whether deliberate or unintentional, culminates in misleading conclusions and steers readers toward an excessively optimistic perspective of the data. The primary objective of this systematic review was to estimate the prevalence and nature of spin within the traumatic brain injury (TBI) literature. Additionally, the identification of associated factors is intended to provide guidance for future research practices. METHODS: The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) recommendations were followed. A search of the MEDLINE/PubMed database was conducted to identify English-language articles published between January 1960 and July 2020. Inclusion criteria encompassed randomized controlled trials (RCTs) that exclusively enrolled TBI patients, investigating various interventions, whether surgical or nonsurgical, and that were published in high-impact journals. Spin was defined as 1) a focus on statistically significant results not based on the primary outcome; 2) interpreting statistically nonsignificant results for a superiority analysis of the primary outcome; 3) claiming or emphasizing the beneficial effect of the treatment despite statistically nonsignificant results; 4) conclusion focused in the per-protocol or as-treated analysis instead of the intention-to-treat (ITT) results; 5) incorrect statistical analysis; or 6) republication of a significant secondary analysis without proper acknowledgment of the primary outcome analysis result. Primary outcomes were those explicitly reported as such in the published article. Studies without a clear primary outcome were excluded. The study characteristics were described using traditional descriptive statistics and an exploratory inferential analysis was performed to identify those associated with spin. The studies' risk of bias was evaluated by the Cochrane Risk of Bias Tool. RESULTS: A total of 150 RCTs were included and 22% (n = 33) had spin, most commonly spin types 1 and 3. The overall risk of bias (p < 0.001), a neurosurgery department member as the first author (p = 0.009), absence of a statistician among authors (p = 0.042), and smaller sample sizes (p = 0.033) were associated with spin. CONCLUSIONS: The prevalence of spin in the TBI literature is high, even at leading medical journals. Studies with higher risks of bias are more frequently associated with spin. Critical interpretation of results and authors' conclusions is advisable regardless of the study design and published journal.


Assuntos
Lesões Encefálicas Traumáticas , Lesões Encefálicas Traumáticas/epidemiologia , Lesões Encefálicas Traumáticas/terapia , Humanos , Prevalência , Ensaios Clínicos Controlados Aleatórios como Assunto
4.
Magn Reson Chem ; 62(8): 583-598, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38557999

RESUMO

Sesquiterpene lactones (SL) represent a class of secondary metabolites found in the Asteraceae family, notable for their unique structures. The SL α-santonin (1) and its derivatives are worthy of mention due to their diverse biological properties. Additionally, 4H-chromenes and 4H-chromones are appealing frameworks holding the capability to be used as structural motifs for new drugs. Furthermore, unambiguous structural elucidation is crucial for developing novel compounds for diverse applications. In this context, it is common to find in the literature molecules erroneously assigned. Therefore, the use of quantum mechanical calculations to simulate NMR chemical shifts has emerged as a valuable strategy. In this work, we conceived the synthesis of two halogenated 4H-chromenediones derived from photosantonic acid (2), a photoproduct arising from irradiation of α-santonin (1) in the ultraviolet region. The structure of the chlorinated and brominated products was determined by NMR analysis, with the aid of quantum mechanical calculations at the B3LYP/6-311 + G(2d,p)//M062x/6-31 + G(d,p) level of theory. All analyses were in agreement and led to the assignment of the brominated 4H-chromene-2,7-dione as (3S,3aS,5aR,9bS)-5a-(2-bromopropan-2-yl)-3-methyl-3,3a,5,5a,8,9b-hexahydro-4H-furo[2,3-f]chromene-2,7-dione (11b) and of the chlorinated 4H-chromene-2,7-dione as (3S,3aS,5aR,9bS)-5a-(2-chloropropan-2-yl)-3-methyl-3,3a,5,5a,8,9b-hexahydro-4H-furo[2,3-f]chromene-2,7-dione (12b). The diastereoselectivities of the reactions were explained based on products and intermediates formation energy calculated using B3LYP/6-31 + G(d,p) as the level of theory. Structures 11b and 12b were identified as the thermodynamic and kinetic products of the reaction among all candidates. Consequently, the strategy utilized in this study is robust and successfully illustrates the use of quantum mechanical calculations in the structural elucidation of new compounds with potential applications as novel drugs or products.

5.
Int J Mol Sci ; 25(3)2024 Jan 24.
Artigo em Inglês | MEDLINE | ID: mdl-38338694

RESUMO

The arbovirus Chikungunya (CHIKV) is transmitted by Aedes mosquitoes in urban environments, and in humans, it triggers debilitating symptoms involving long-term complications, including arthritis and Guillain-Barré syndrome. The development of antiviral therapies is relevant, as no efficacious vaccine or drug has yet been approved for clinical application. As a detailed map of molecules underlying the viral infection can be obtained from the metabolome, we validated the metabolic signatures of Vero E6 cells prior to infection (CC), following CHIKV infection (CV) and also upon the inclusion of the nsP2 protease inhibitor wedelolactone (CWV), a coumestan which inhibits viral replication processes. The metabolome groups evidenced significant changes in the levels of lactate, myo-inositol, phosphocholine, glucose, betaine and a few specific amino acids. This study forms a preliminary basis for identifying metabolites through HR-MAS NMR (High Resolution Magic Angle Spinning Nuclear Magnetic Ressonance Spectroscopy) and proposing the affected metabolic pathways of cells following viral infection and upon incorporation of putative antiviral molecules.


Assuntos
Aedes , Febre de Chikungunya , Animais , Chlorocebus aethiops , Humanos , Células Vero , Metabolômica , Replicação Viral , Antivirais/farmacologia
6.
Neurosurg Rev ; 47(1): 47, 2024 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-38221545

RESUMO

BACKGROUND AND OBJECTIVES: High-grade gliomas (HGGs) are aggressive tumors of the central nervous system that cause significant morbidity and mortality. Despite advances in surgery and radiation therapy (RT), HGG still has a high incidence of recurrence and treatment failure. Intraoperative radiotherapy (IORT) has emerged as a promising therapeutic approach to achieve local tumor control while sparing normal brain tissue from radiation-induced damage. METHODS: A systematic review and meta-analysis were conducted following PRISMA guidelines to evaluate the use of IORT for HGG. Eligible studies were included based on specific criteria, and data were independently extracted. Outcomes of interest included complications, IORT failure, survival rates at 12 and 24 months, and mortality. RESULTS: Sixteen studies comprising 436 patients were included. The overall complication rate after IORT was 17%, with significant heterogeneity observed. The IORT failure rate was 77%, while the survival rates at 12 and 24 months were 74% and 24%, respectively. The mortality rate was 62%. CONCLUSION: This meta-analysis suggests that IORT may be a promising adjuvant treatment for selected patients with HGG. Despite the high rate of complications and treatment failures, the survival outcomes were comparable or even superior to conventional methods. However, the limitations of the study, such as the lack of a control group and small sample sizes, warrant further investigation through prospective randomized controlled trials to better understand the specific patient populations that may benefit most from IORT. However, the limitations of the study, such as the lack of a control group and small sample sizes, warrant further investigation. Notably, the ongoing RP3 trial (NCT02685605) is currently underway, with the aim of providing a more comprehensive understanding of IORT. Moreover, future research should focus on managing complications associated with IORT to improve its safety and efficacy in treating HGG.


Assuntos
Neoplasias Encefálicas , Glioma , Humanos , Neoplasias Encefálicas/radioterapia , Neoplasias Encefálicas/cirurgia , Neoplasias Encefálicas/tratamento farmacológico , Estudos Prospectivos , Glioma/radioterapia , Glioma/cirurgia , Recidiva Local de Neoplasia , Radioterapia/efeitos adversos
7.
Rev. Baiana Enferm. (Online) ; 38: e54897, 2024. tab
Artigo em Português | LILACS, BDENF - Enfermagem | ID: biblio-1559301

RESUMO

Objetivo: descrever a prevalência de casos graves pelo SARS-Cov-2 e fatores associados à ocorrência em crianças e adolescentes. Método: estudo transversal, num hospital pediátrico, com 236 crianças e adolescentes com COVID-19 entre março-2020 até fevereiro-2022. Resultados: a prevalência de casos graves da COVID-19 foi de 37%. A maior frequência foram do sexo masculino (41%), até 1 ano de idade (41,8%) e municípios circunvizinhos (46,5%). As manifestações clínicas em até 72 horas após hospitalização, associados aos casos graves foram: desconforto respiratório (RPb: 1,91; IC 95% 1,36 - 2,67), saturação de O2 < 92% (RPb: 9,27 IC 95% 5,99 - 14,35), necessidade de cuidados intensivos (RPb: 5,25; IC 95% 3,87 - 7,12) e comorbidades (RPb: 1,73 IC 95% 1,25 - 2,40). Os desfechos, óbito/transferência, associaram-se com maior proporção de casos graves. Conclusão: conhecer o perfil de casos de COVID-19 na população pediátrica e fatores associados pode contribuir para revisar processos a fim de manejo adequado dos casos.


Objetivo: describir la prevalencia de casos graves por el SARS-Cov-2 y factores asociados a la ocurrencia en niños y adolescentes. Método: estudio transversal, en un hospital pediátrico, con 236 niños y adolescentes con COVID-19 entre marzo-2020 hasta febrero-2022. Resultados: la prevalencia de casos graves de COVID-19 fue del 37%. La mayor frecuencia fueron del sexo masculino (41%), hasta 1 año de edad (41,8%) y municipios circundantes (46,5%). Las manifestaciones clínicas en hasta 72 horas después de la hospitalización, asociados a los casos graves fueron: malestar respiratorio (RPb: 1,91; IC 95% 1,36 - 2,67), saturación de O2 < 92% (RPb: 9,27 IC 95% 5,99 - 14,35), necesidad de cuidados intensivos (RPb: 5,25; IC 95% 3,87 - 7,12) y comorbilidades (RPb: 1,73 IC 95% 1,25 - 2,40). Los resultados, muerte/transferencia, se asociaron con mayor proporción de casos graves. Conclusión: conocer el perfil de casos de COVID-19 en la población pediátrica y factores asociados puede contribuir para revisar procesos a fin de manejo adecuado de los casos.


Objective: to describe the prevalence of severe cases by SARS-Cov-2 and factors associated with the occurrence in children and adolescents. Method: cross-sectional study, in a pediatric hospital, with 236 children and adolescents with COVID-19 between March 2020 and February 2022. Results: the prevalence of severe cases of COVID-19 was 37%. The highest frequency was male (41%), up to 1 year of age (41.8%) and surrounding cities (46.5%). Clinical manifestations within 72 hours of hospitalization, associated with severe cases, were respiratory distress (PRc: 1.91; 95% CI 1.36 -2.67), O2saturation < 92% (PRc: 9.27 95% CI 5.99 - 14.35), need for intensive care (PRc: 5.25; 95% CI 3.7 - 87) and comorbidities (PRc: 1.73 95% CI 1.25 - 2.40). The outcomes death/transfer were associated with a higher proportion of severe cases. Conclusion: knowing the profile of COVID-19 cases in the pediatric population and associated factors can contribute to review processes for proper management of cases.


Assuntos
Humanos , Masculino , Feminino , Recém-Nascido , Lactente , Pré-Escolar , Criança , Adolescente , COVID-19/complicações , Hospitais Pediátricos , Prevalência , Estudos Transversais
8.
Braz Dent J ; 34(5): 115-124, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38133466

RESUMO

Studies have reported changes in the epidemiological profile of patients with oral cancer in recent decades, especially regarding gender and age. This study aimed to evaluate a historical series of oral malignant lesions prevalence over six decades and define characteristics associated with the occurrence, mainly, of oral squamous cell carcinoma (OSCC). A retrospective review of histopathological records from 1953 to 2019 was conducted in three oral pathology laboratories in South Brazil about age, sex, anatomical site, clinical aspect, and histopathological diagnosis. Descriptive and analytical analyses were performed comparing the histopathological diagnoses with other variables. Multivariable logistic regression was applied to determine the associated predictors of OSCC. Of the 53,065 records available in the institutions, 986 were oral malignant tumors (including all malignant neoplasms), representing 1.86% of all diagnoses. The occurrence of OSCC in the 1960's was 80.0%, decreasing over time reaching the lowest percentage of cases in the 1990's (75.8%) and significantly increasing to 88.7% in the 2010s. Females had a lower chance than males of having OSCC independently of the decade (odds ratio=0.30, p<0.001). This was the same for older individuals compared to those younger than 40 years. No interactions between sex, age, and decade were observed. The number of diagnoses of oral malignant lesions increased over time, and the occurrence of OSCC varied. Older individuals and males had higher chances of having OSCC independently of the decade. Therefore, in this study sample, no changes were observed in the epidemiological profile over the years concerning these predictors.


Assuntos
Carcinoma de Células Escamosas , Neoplasias Bucais , Masculino , Feminino , Humanos , Neoplasias Bucais/epidemiologia , Neoplasias Bucais/patologia , Estudos Retrospectivos , Carcinoma de Células Escamosas/epidemiologia , Carcinoma de Células Escamosas/patologia , Prevalência , Brasil/epidemiologia
9.
Braz. dent. j ; Braz. dent. j;34(5): 115-124, Sept.-Oct. 2023. tab, graf
Artigo em Inglês | LILACS-Express | LILACS, BBO - Odontologia | ID: biblio-1528013

RESUMO

Abstract Studies have reported changes in the epidemiological profile of patients with oral cancer in recent decades, especially regarding gender and age. This study aimed to evaluate a historical series of oral malignant lesions prevalence over six decades and define characteristics associated with the occurrence, mainly, of oral squamous cell carcinoma (OSCC). A retrospective review of histopathological records from 1953 to 2019 was conducted in three oral pathology laboratories in South Brazil about age, sex, anatomical site, clinical aspect, and histopathological diagnosis. Descriptive and analytical analyses were performed comparing the histopathological diagnoses with other variables. Multivariable logistic regression was applied to determine the associated predictors of OSCC. Of the 53,065 records available in the institutions, 986 were oral malignant tumors (including all malignant neoplasms), representing 1.86% of all diagnoses. The occurrence of OSCC in the 1960's was 80.0%, decreasing over time reaching the lowest percentage of cases in the 1990's (75.8%) and significantly increasing to 88.7% in the 2010s. Females had a lower chance than males of having OSCC independently of the decade (odds ratio=0.30, p<0.001). This was the same for older individuals compared to those younger than 40 years. No interactions between sex, age, and decade were observed. The number of diagnoses of oral malignant lesions increased over time, and the occurrence of OSCC varied. Older individuals and males had higher chances of having OSCC independently of the decade. Therefore, in this study sample, no changes were observed in the epidemiological profile over the years concerning these predictors.


Resumo Alguns estudos relataram mudanças no perfil epidemiológico dos pacientes com câncer bucal nas últimas décadas, principalmente quanto ao gênero e a idade. Este estudo teve como objetivo avaliar, em uma série histórica, a prevalência de todas as lesões malignas bucais ao longo de seis décadas e definir características associadas na ocorrência, principalmente, de carcinoma espinocelular (CEC). Um levantamento retrospectivo dos registros histopatológicos de 1953 a 2019 foi realizado em três laboratórios de Patologia Bucal no Sul do Brasil em relação à idade, gênero, sítio anatômico, aspecto clínico e diagnóstico histopatológico. Análises descritivas e analíticas foram realizadas comparando-se os diagnósticos histopatológicos com as outras variáveis. A regressão logística multivariada foi aplicada para determinar os possíveis preditores associados ao CEC. Dos 53.065 prontuários disponíveis nas instituições, 986 eram tumores malignos bucais (incluindo todas as neoplasias malignas), representando 1,86% de todos os diagnósticos. A ocorrência de CEC na década de 1960 foi de 80,0%, diminuindo ao longo do tempo, atingindo o menor percentual de casos na década de 1990 (75,8%) e aumentando significativamente para 88,7% na década de 2010. As mulheres tiveram menor risco de desenvolver CEC do que os homens, independentemente da década (OR=0,30, p<0,001). Este foi o mesmo para indivíduos com idade mais avançada em comparação com aqueles com menos de 40 anos de idade. Não foram observadas interações entre gênero, idade e década. O número de diagnósticos de lesões malignas bucais aumentou ao longo das décadas e a ocorrência de CEC variou. Indivíduos com mais de 40 anos e do sexo masculino tiveram maiores chances de ter CEC, independentemente da década analisada. Portanto, nessa amostra estudada, não foram observadas mudanças no perfil epidemiológico ao longo dos anos com relação a esses preditores.

10.
PLoS One ; 18(8): e0288515, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37561781

RESUMO

Urban parks have been studied for their effects on health and the environment. Accessing park data from reliable and comparable sources remains challenging, reinforcing the importance of standardized search tools, notably in Latin America. We designed a systematized methodology to identify processes of accessing, collecting, verifying, and harmonizing urban park spatial data in all Brazilian capitals included in the Urban Health in Latin America (SALURBAL) project. We developed a research protocol using official and non-official sources combining the results of Google Maps (GMaps) points and OpenStreetMap (OSM) polygons-GMaps-OSM. Descriptive analyses included the frequency of the distribution of parks before and after harmonization stratified by data source. We used the intraclass correlation coefficient (ICC) to assess agreement in the area between official and GMaps-OSM data. Official data were obtained for 16 cities; for the remaining 11 capitals, we used GMaps-OSM. After verification and harmonization, 302 urban parks were obtained from official data and 128 from GMaps-OSM. In a sub-study of the 16 cities with official data (n = 302 parks), we simulated a collection of non-official data using GMaps-OSM and OSM only. From GMaps-OSM, we obtained 142 parks, and from OSM, 230 parks. Statistical analysis showed a better agreement between official data and OSM. After completing verification and harmonization, the complete dataset (official and GMaps-OSM) included 430 urban parks with a total area of 145.14 km2. The mean number of parks across cities was 16, with a mean size area of 0.33 km2. The median number of parks was nine, with a median area of 0.07 km2. This study highlights the importance of creating mechanisms to access, collect, harmonize, and verify urban park data, which is essential for examining the impact of parks on health. It also stresses the importance of providing reliable urban park spatial data for city officials.


Assuntos
Parques Recreativos , Saúde da População Urbana , Humanos , Brasil , Cidades , Coleta de Dados , População Urbana
11.
Artigo em Inglês | MEDLINE | ID: mdl-37205869

RESUMO

Introduction: Diabetic neuropathies are the most prevalent chronic complications of diabetes, characterized by pain and substantial morbidity. Although many drugs have been approved for the treatment of this type of pain, including gabapentin, tramadol (TMD), and classical opioids, it is common to report short-term results or potentially severe side effects. TMD, recommended as a second-line treatment can lead to unwanted side effects. Cannabidiol (CBD) has been gaining attention recently due to its therapeutic properties, including pain management. This study aimed to characterize the pharmacological interaction between CBD and TMD over the mechanical allodynia associated with experimental diabetes using isobolographic analysis. Materials and Methods: After diabetes induction by streptozotocin (STZ), diabetic rats were systemically treated with CBD or TMD alone or in combination (doses calculated based on linear regression of effective dose 40% [ED40]) and had the mechanical threshold evaluated using the electronic Von Frey apparatus. Both experimental and theoretical additive ED40 values (Zmix and Zadd, respectively) were determined for the combination of CBD plus TMD in this model. Results: Acute treatment with CBD (3 or 10 mg/kg) or TMD (2.5, 5, 10, or 20 mg/kg) alone or in combination (0.38+1.65 or 1.14+4.95 mg/kg) significantly improved the mechanical allodynia in STZ-diabetic rats. Isobolographic analysis revealed that experimental ED40 of the combination (Zmix) was 1.9 mg/kg (95% confidence interval [CI]=1.2-2.9) and did not differ from the theoretical additive ED40 2.0 mg/kg (95% CI=1.5-2.8; Zadd), suggesting an additive antinociceptive effect in this model. Conclusions: Using an isobolographic analysis, these results provide evidence of additive pharmacological interaction between CBD and TMD over the neuropathic pain associated with experimental diabetes induced by STZ.

12.
Front Behav Neurosci ; 17: 1059029, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36926582

RESUMO

Introduction: Skilled walking is influenced by memory, stress, and anxiety. While this is evident in cases of neurological disorders, memory, and anxiety traits may predict skilled walking performance even in normal functioning. Here, we address whether spatial memory and anxiety-like behavior can predict skilled walking performance in mice. Methods: A cohort of 60 adult mice underwent a behavioral assessment including general exploration (open field), anxiety-like behavior (elevated plus maze), working and spatial memory (Y-maze and Barnes maze), and skilled walking performance (ladder walking test). Three groups were established based on their skilled walking performance: superior (SP, percentiles ≥75), regular (RP, percentiles 74-26), and inferior (IP, percentiles ≤25) performers. Results: Animals from the SP and IP groups spent more time in the elevated plus maze closed arms compared to the RP group. With every second spent in the elevated plus maze closed arms, the probability of the animal exhibiting extreme percentiles in the ladder walking test increased by 1.4%. Moreover, animals that spent 219 s (73% of the total time of the test) or more in those arms were 4.67 times more likely to exhibit either higher or lower percentiles of skilled walking performance. Discussion: We discuss and conclude anxiety traits may influence skilled walking performance in facility-reared mice.

13.
Mol Omics ; 19(1): 27-34, 2023 01 16.
Artigo em Inglês | MEDLINE | ID: mdl-36172788

RESUMO

It was demonstrated that effervescent glutamine supplementation in HIV+ individuals treated with antiretroviral therapy (ART) increased CD4+ T lymphocytes, decreased inflammation biomarkers, and brought health benefits. This pilot study aimed to explore serum metabolite variations in the HIV+ group under ART after 30 days of supplementation with glutamine, and in comparison to the matched HIV- group. The group of HIV+ showed lower levels of choline, creatine, pyruvate, glutamate, lysine, and tyrosine when compared to the HIV- group. Glucose, lipids, lactate, glutamine, phenylalanine, threonine, and phenylalanine/tyrosine were higher in HIV+ patients under long ART. Serum metabolome variations were shown to be consistent with the health improvements observed in the HIV+ group after effervescent glutamine supplementation, which might aid in ART in HIV+ individuals.


Assuntos
Glutamina , Infecções por HIV , Humanos , Glutamina/uso terapêutico , Projetos Piloto , Infecções por HIV/tratamento farmacológico , Infecções por HIV/metabolismo , Tirosina/uso terapêutico , Fenilalanina/uso terapêutico , Administração Oral
14.
Photochem Photobiol ; 99(2): 732-741, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-35944220

RESUMO

Hydroxypyranoflavylium (HPF) cations are synthetic analogs possessing the same basic chromophore as the pyranoanthocyanins that form during the maturation of red wine. HPF cations absorb strongly in the visible spectral region, and most are fluorescent, triplet-sensitize singlet oxygen formation in solution and are strong photooxidants, properties that are desirable in a sensitizer for photodynamic therapy (PDT). The results of this study demonstrate that several simple HPF dyes can indeed function as PDT sensitizers. Of the eight HPF cations investigated in this work, four were phototoxic to a human cervical adenocarcinoma cell line (HeLa) at the 1-10 µmol dm-3 level, while only one of the eight compounds showed noticeable cytotoxicity in the dark. Neither a Type I nor a Type II mechanism can adequately rationalize the differences in phototoxicity of the compounds. Colocalization experiments with the most phototoxic compound demonstrated the affinity of the dye for both the mitochondria and lysosomes of HeLa cells. The fact that relatively modest structural differences, e.g., the exchange of an electron-donating substituent for an electron-withdrawing substituent, can cause profound differences in the phototoxicity, together with the relatively facile synthesis of substituted HPF cations, makes them interesting candidates for further evaluation as PDT sensitizers.


Assuntos
Fotoquimioterapia , Fármacos Fotossensibilizantes , Humanos , Fármacos Fotossensibilizantes/química , Fotoquimioterapia/métodos , Células HeLa , Corantes/química , Oxigênio Singlete/metabolismo
15.
Rev Rene (Online) ; 24: e85215, 2023. graf
Artigo em Português | LILACS, BDENF - Enfermagem | ID: biblio-1449063

RESUMO

RESUMO Objetivo compreender a percepção dos enfermeiros sobre a complexidade do cuidado para o controle térmico do recém-nascido prematuro. Métodos estudo qualitativo realizado com 13 enfermeiros de maternidade pública, por meio de entrevista virtual, com roteiro semiestruturado, submetido à Análise de Conteúdo e interpretado pelo suporte teórico do modelo do sistema adaptativo complexo de cuidado. Resultados os fatores presentes nos cuidados dos enfermeiros no controle térmico do recém-nascido prematuro estão relacionados à complexidade permeada por fatores ambientais como a temperatura da unidade e a distribuição das correntes de ar condicionado; fatores institucionais como a disponibilização e uso correto de tecnologias, e aos relacionados com o profissional, como atuação, treinamento e capacitação. Conclusão adequar a temperatura da unidade; melhor distribuição das correntes do ar condicionado; a disponibilidade de tecnologias; política de educação continuada no serviço; treinamentos de manuseio dos equipamentos; fiscalização e exigência de manutenção preventiva e corretiva dos aparelhos podem influenciar a redução dos eventos de instabilidade térmica do recém-nascido prematuro. Contribuições para a prática estimular a qualificação profissional, planejamento de ações intersetoriais para a estruturação tecnológica e manutenção preventiva das unidades, sistematização da assistência ao recém-nascido prematuro no controle térmico minimizando o risco de morbimortalidade neonatal por instabilidade térmica.


ABSTRACT Objective to understand the perception of nurses about the complexity of care for thermal control of the premature infant. Methods qualitative study conducted with 13 nurses from a public maternity hospital, through virtual interviews, with semi-structured script, submitted to Content Analysis and interpreted by the theoretical support of the complex adaptive care system model. Results the factors present in nurses' care in thermal control of premature infants are related to the complexity permeated by environmental factors such as the temperature of the unit and distribution of air conditioning currents; institutional factors such as the availability and correct use of technologies, and those related to the professional, such as performance, training, and qualification. Conclusion adjusting the temperature of the unit; better distribution of the air conditioning currents; availability of technologies; a policy of continued education in the service; training in handling the equipment; supervision and requirement for preventive and corrective maintenance of the devices can influence the reduction of thermal instability events in premature infants. Contributions to practice stimulating professional qualification, planning of intersectoral actions for technological structuring and preventive maintenance of the units, systematization of assistance to premature infants in thermal control minimizing risk of neonatal morbimortality due to thermal instability.


Assuntos
Humanos , Recém-Nascido , Regulação da Temperatura Corporal , Recém-Nascido Prematuro , Enfermagem Neonatal , Dinâmica não Linear , Neonatologia
16.
Rev. bras. oftalmol ; 82: e0038, 2023. tab
Artigo em Português | LILACS-Express | LILACS | ID: biblio-1449765

RESUMO

RESUMO Objetivo Avaliar e caracterizar a qualidade da assistência oftalmológica ofertada em uma unidade de serviços ambulatoriais da Atenção Secundária do Sistema Único de Saúde na percepção dos usuários e/ou dos responsáveis por esses usuários. Métodos Foi realizado estudo seccional de prevalência analítica entre usuários assistidos no período de setembro de 2019 a março de 2020 em um dos seis serviços de assistência oftalmológica ofertado pelo Sistema Único de Saúde, no município de Vitória da Conquista (BA). Foram avaliadas as condições demográficas e socioeconômicas e a autopercepção da saúde. Também foram avaliadas as características e os níveis de qualidade da assistência à saúde oftalmológica. A coleta das informações ocorreu por meio de entrevista telefônica. Resultados Participaram do estudo 389 usuários e/ou responsáveis. Observaram-se elevados níveis de satisfação, considerando as perguntas que compõem o constructo do instrumento. Identificaram-se níveis de qualidade comprometidos em relação à liberdade de escolher seu prestador de cuidado ocular (154; 39,7%). Menores níveis de satisfação associaram-se com as variáveis sexo masculino (razão de chance de 1,66; IC95% 1,04-2,65; p=0,033) e raça autodeclada branca (razão de chance de 6,89; IC95% 4,00-11,86; p=0,000). Conclusão Os usuários relataram bons níveis de satisfação da assistência à saúde oftalmológica. Observaram-se maiores chances de menores níveis de satisfação entre homens e aqueles com raça autodeclarada branca.


ABSTRACT Objective To evaluate and characterize the quality of ophthalmic care offered in an outpatient service unit of the SUS secondary care according to the perception of users and/or those responsible for these users. Methods A cross-sectional study of analytical prevalence was carried out among users assisted from September 2019 to March 2020, in one of the six ophthalmic care services offered by the SUS, in the municipality of Vitória da Conquista (BA), Brazil. Demographic and socioeconomic conditions, as well as self-perception of health, were evaluated. The characteristics and quality levels of ophthalmic health care were also evaluated. Data collection took place through a telephone interview. Results A total of 389 users and/or guardians participated in the study. Participants reported high levels of satisfaction, considering the questions that make up the instrument's construct. Compromised quality levels were observed in relation to the freedom to choose their eye care provider (n=154; 39.7%). Lower levels of satisfaction were associated with the variables male gender (OR=1.66; 95%CI=1.04-2.65; p=0.033) and self-reported white race (OR=6.89; 95%CI=4, 00-11.86; p=0.000). Conclusion Users reported good levels of satisfaction with eye health care. There were greater chances of lower levels of satisfaction among men and among those with a self-reported white race.

17.
Biomedicines ; 10(12)2022 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-36551847

RESUMO

Cancer is one of the leading causes of death in children and adolescents worldwide; among the types of liver cancer, hepatoblastoma (HBL) is the most common in childhood. Although it affects only two to three individuals in a million, it is mostly asymptomatic at diagnosis, so by the time it is detected it has already advanced. There are specific recommendations regarding HBL treatment, and ongoing studies to stratify the risks of HBL, understand the pathology, and predict prognostics and survival rates. Although magnetic resonance imaging spectroscopy is frequently used in diagnostics of HBL, high-resolution magic-angle-spinning (HR-MAS) NMR spectroscopy of HBL tissues is scarce. Using this technique, we studied the alterations among tissue metabolites of ex vivo samples from (a) HBL and non-cancer liver tissues (NCL), (b) HBL and adjacent non-tumor samples, and (c) two regions of the same HBL samples, one more centralized and the other at the edge of the tumor. It was possible to identify metabolites in HBL, then metabolites from the HBL center and the border samples, and link them to altered metabolisms in tumor tissues, highlighting their potential as biochemical markers. Metabolites closely related to liver metabolisms such as some phospholipids, triacylglycerides, fatty acids, glucose, and amino acids showed differences between the tissues.

18.
Molecules ; 27(23)2022 Nov 23.
Artigo em Inglês | MEDLINE | ID: mdl-36500237

RESUMO

Molecular docking, molecular dynamics (MD) simulations and the linear interaction energy (LIE) method were used here to predict binding modes and free energy for a set of 1,2,3-triazole-based KA analogs as potent inhibitors of Tyrosinase (TYR), a key metalloenzyme of the melanogenesis process. Initially, molecular docking calculations satisfactorily predicted the binding mode of evaluated KA analogs, where the KA part overlays the crystal conformation of the KA inhibitor into the catalytic site of TYR. The MD simulations were followed by the LIE method, which reproduced the experimental binding free energies for KA analogs with an r2 equal to 0.97, suggesting the robustness of our theoretical model. Moreover, the van der Waals contributions performed by some residues such as Phe197, Pro201, Arg209, Met215 and Val218 are responsible for the binding recognition of 1,2,3-triazole-based KA analogs in TYR catalytic site. Finally, our calculations provide suitable validation of the combination of molecular docking, MD, and LIE approaches as a powerful tool in the structure-based drug design of new and potent TYR inhibitors.


Assuntos
Simulação de Dinâmica Molecular , Triazóis , Simulação de Acoplamento Molecular , Triazóis/farmacologia , Pironas/farmacologia , Pironas/química , Monofenol Mono-Oxigenase , Ligação Proteica
19.
Rev Lat Am Enfermagem ; 30(spe): e3843, 2022.
Artigo em Inglês, Português, Espanhol | MEDLINE | ID: mdl-36449929

RESUMO

OBJECTIVE: understand the impacts of pregnancy on the lives of quilombola adolescents. METHOD: this is a qualitative study using an exploratory descriptive design. Ten quilombola mothers who experienced pregnancy during adolescence participated in this study. Data were collected through semi-structured interviews and then submitted to content analysis. RESULTS: three categories were identified, showing the knowledge of the participants about being a quilombola and about the impacts on their lives after discovering they were pregnant and how they handled the fact of being a mother-adolescent according to the adaptations and expectations of their new phase. CONCLUSION: pregnancy in adolescence had impacts on several aspects of the lives of adolescents, with psychological, educational, socioeconomic, and family implications, as well as new responsibilities. Also, this study highlights the role of pregnant adolescent reception of nursing professionals to meet the individual needs of adolescents and develop prevention strategies to help reduce pregnancy among quilombola adolescents. HIGHLIGHTS: (1) Impacts of pregnancy on the daily routine of quilombola adolescents.(2) Psychological, educational, socioeconomic, and family implications.(3) Discovering motherhood and assuming new responsibilities.(4) Developing strategies to prevent pregnancy in quilombola adolescents.(5) Nursing assumes the role of reception of these pregnant quilombola adolescents.


Assuntos
Conhecimento , Mães , Feminino , Gravidez , Humanos , Adolescente , Escolaridade , Pesquisa Qualitativa
20.
Acta Neuropsychiatr ; : 1-9, 2022 Nov 23.
Artigo em Inglês | MEDLINE | ID: mdl-36416534

RESUMO

OBJECTIVE: The cingulate gyrus is implicated in the neurobiology of addiction, such as chronic cocaine consumption. Early life stress (ELS) is an important moderator of cocaine use disorder (CUD). Therefore, we investigated the effect of CUD on cingulate cortical thickness and tested whether a history of ELS could influence the effects of CUD. METHODS: Participants aged 18-50 years (78 with CUD due to crack cocaine consumption and 53 healthy controls) underwent magnetic resonance imaging and the cingulate thickness (rostral anterior, caudal anterior, posterior, and isthmus regions) was analysed. The clinical assessment comprised the Childhood Trauma Questionnaire (CTQ) and the Addiction Severity Index. Group comparisons adjusting by sex, age, and education were performed. Mediation models were generated where lifetime cocaine use, CTQ score, and cortical thickness corresponded to the independent variable, intermediary variable, and outcome, respectively. RESULTS: Group comparisons revealed significant differences in six out of eight cingulate cortices, showing lower thickness in the CUD group. Furthermore, years of regular cocaine use was the variable most associated with cingulate thickness. Negative correlations were found between CTQ scores and the isthmus cingulate (right hemisphere), as well as with the rostral anterior cingulate (left hemisphere). In the mediation analysis, we observed a significant negative direct effect of lifetime cocaine use on the isthmus cingulate and an indirect effect of cocaine use mediated by CTQ score. CONCLUSION: Our findings suggest that a history of ELS could aggravate the negative effects of chronic cocaine use on the cingulate gyrus, particularly in the right isthmus cingulate cortex.

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