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1.
Food Res Int ; 188: 114496, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38823843

RESUMO

Agro-industrial co-products, such as fish gelatin, stand out for their capacity in forming biopolymeric films, being biocompatible and non-toxic; however, its hydrophilicity poses a challenge. Essential oils, rich in bioactives, attract research interest aiming to enhance the protective barrier of films and enable their application in packaging. This study produced films based on cross-linked Nile tilapia skin gelatin, incorporating garlic essential oil. Gelatin obtained through partial collagen hydrolysis from the fish skin and cross-linked with gallic acid had hydroxyproline content of 10.02 g 100 g-1 and gel strength of 287 g, which were consistent with other studies. Oil extraction used supercritical CO2 as a solvent and ethanol as a cosolvent, following a factorial experimental design, evaluating the extraction temperature (40 °C and 70 °C) and cosolvent ratio (1:1 and 1:3), with three central points. Extraction was successful, with higher yields on a dry basis at 70 °C (88.35 %), using a 1:1 cosolvent ratio. Films incorporated with oil exhibited lower water vapor permeability (WVP) than those with only cross-linked gelatin (1.59 (g m-1 s-1 Pa-1) 1011). The film with the most suitable tensile strength (19.07 MPa), elongation (120.91 %), and WVP (1.09 (g m-1 s-1 Pa-1) 1011) properties contained garlic oil extracted at the central point (55 °C and 1:2). Thermal analysis indicated increased melting temperatures in films with added oil, suggesting low thermal degradation. These results suggest that garlic oil addition can improve the properties of fish gelatin-based films, making them promising for biodegradable packaging.


Assuntos
Embalagem de Alimentos , Alho , Gelatina , Óleos Voláteis , Permeabilidade , Gelatina/química , Óleos Voláteis/química , Animais , Alho/química , Embalagem de Alimentos/métodos , Resistência à Tração , Vapor , Sulfetos/química , Interações Hidrofóbicas e Hidrofílicas , Pele/química
2.
Nat Commun ; 15(1): 3872, 2024 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-38719797

RESUMO

The gut microbiota and microglia play critical roles in Alzheimer's disease (AD), and elevated Bacteroides is correlated with cerebrospinal fluid amyloid-ß (Aß) and tau levels in AD. We hypothesize that Bacteroides contributes to AD by modulating microglia. Here we show that administering Bacteroides fragilis to APP/PS1-21 mice increases Aß plaques in females, modulates cortical amyloid processing gene expression, and down regulates phagocytosis and protein degradation microglial gene expression. We further show that administering Bacteroides fragilis to aged wild-type male and female mice suppresses microglial uptake of Aß1-42 injected into the hippocampus. Depleting murine Bacteroidota with metronidazole decreases amyloid load in aged 5xFAD mice, and activates microglial pathways related to phagocytosis, cytokine signaling, and lysosomal degradation. Taken together, our study demonstrates that members of the Bacteroidota phylum contribute to AD pathogenesis by suppressing microglia phagocytic function, which leads to impaired Aß clearance and accumulation of amyloid plaques.


Assuntos
Doença de Alzheimer , Peptídeos beta-Amiloides , Modelos Animais de Doenças , Camundongos Transgênicos , Microglia , Fagocitose , Placa Amiloide , Animais , Microglia/metabolismo , Microglia/efeitos dos fármacos , Doença de Alzheimer/metabolismo , Doença de Alzheimer/microbiologia , Doença de Alzheimer/patologia , Peptídeos beta-Amiloides/metabolismo , Placa Amiloide/metabolismo , Feminino , Camundongos , Masculino , Bacteroides fragilis/metabolismo , Microbioma Gastrointestinal , Humanos , Camundongos Endogâmicos C57BL , Hipocampo/metabolismo , Hipocampo/patologia
3.
Oncology (Williston Park) ; 38(3): 115-116, 2024 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-38517411

RESUMO

In a recent Hot Topics article, reimbursement rates for Medicare physicians are discussed, and how it will impact their practice.


Assuntos
Medicare , Médicos , Idoso , Estados Unidos , Humanos , Mecanismo de Reembolso , Reembolso de Seguro de Saúde
4.
Oncology (Williston Park) ; 38(3): 115-116, 2024 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-38517413

RESUMO

In a recent Hot Topics article, reimbursement rates for Medicare physicians are discussed, and how it will impact their practice.


Assuntos
Medicare , Médicos , Idoso , Estados Unidos , Humanos , Mecanismo de Reembolso , Reembolso de Seguro de Saúde
5.
Drugs R D ; 24(1): 117-121, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38413481

RESUMO

BACKGROUND: Selective serotonin reuptake inhibitors (SSRI) are commonly used for the treatment of depression and anxiety. Inhibition of serotonin reuptake in platelets increases bleeding risk in patients taking SSRIs. CASE: Here, we present the case of a 52-year-old patient who developed severe postsurgical bleeding requiring blood transfusion following panniculectomy. CONCLUSION: SSRI-induced bleeding is dose-related and strongly influenced by individual variations in drug metabolizing enzymes and transporters. Supplementary file1 (MP4 8441 KB).

6.
Oncogene ; 43(11): 804-820, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38279062

RESUMO

HJURP is overexpressed in several cancer types and strongly correlates with patient survival. However, the mechanistic basis underlying the association of HJURP with cancer aggressiveness is not well understood. HJURP promotes the loading of the histone H3 variant, CENP-A, at the centromeric chromatin, epigenetically defining the centromeres and supporting proper chromosome segregation. In addition, HJURP is associated with DNA repair but its function in this process is still scarcely explored. Here, we demonstrate that HJURP is recruited to DSBs through a mechanism requiring chromatin PARylation and promotes epigenetic alterations that favor the execution of DNA repair. Incorporation of HJURP at DSBs promotes turnover of H3K9me3 and HP1, facilitating DNA damage signaling and DSB repair. Moreover, HJURP overexpression in glioma cell lines also affected global structure of heterochromatin independently of DNA damage induction, promoting genome-wide reorganization and assisting DNA damage response. HJURP overexpression therefore extensively alters DNA damage signaling and DSB repair, and also increases radioresistance of glioma cells. Importantly, HJURP expression levels in tumors are also associated with poor response of patients to radiation. Thus, our results enlarge the understanding of HJURP involvement in DNA repair and highlight it as a promising target for the development of adjuvant therapies that sensitize tumor cells to irradiation.


Assuntos
Cromatina , Glioma , Humanos , Centrômero/metabolismo , Proteína Centromérica A/genética , Proteína Centromérica A/metabolismo , Cromatina/genética , Proteínas Cromossômicas não Histona/genética , Proteínas Cromossômicas não Histona/metabolismo , Reparo do DNA/genética , Proteínas de Ligação a DNA/genética , Proteínas de Ligação a DNA/metabolismo , Glioma/genética
7.
Ann Neurol ; 95(2): 400-406, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37962377

RESUMO

Spinocerebellar ataxia type 3/Machado-Joseph disease is the most common autosomal dominant ataxia. In view of the development of targeted therapies, knowledge of early biomarker changes is needed. We analyzed cross-sectional data of 292 spinocerebellar ataxia type 3/Machado-Joseph disease mutation carriers. Blood concentrations of mutant ATXN3 were high before and after ataxia onset, whereas neurofilament light deviated from normal 13.3 years before onset. Pons and cerebellar white matter volumes decreased and deviated from normal 2.2 years and 0.6 years before ataxia onset. We propose a staging model of spinocerebellar ataxia type 3/Machado-Joseph disease that includes a biomarker stage characterized by objective indicators of neurodegeneration before ataxia onset. ANN NEUROL 2024;95:400-406.


Assuntos
Ataxia Cerebelar , Doença de Machado-Joseph , Humanos , Doença de Machado-Joseph/genética , Estudos Transversais , Ataxia , Biomarcadores
9.
Cien Saude Colet ; 28(10): 2931-2940, 2023 Oct.
Artigo em Português, Inglês | MEDLINE | ID: mdl-37878935

RESUMO

This study examined the prevalence of anxiety and depression associated with Community Health Workers' (CHWs') working conditions in the context of the COVID-19 pandemic. This cross-sectional study was carried out in the north of Minas Gerais, Brazil by applying a questionnaire addressing sociodemographic conditions, command of technologies and working conditions during the pandemic, as well as the State-Trait Anxiety Inventory and the Patient Health Questionnare-9 (PHQ-9). Descriptive and multiple Poisson regression analyses were performed with robust variance, to a 5% level of significance (p < 0.05) for the final model. A total of 1,220 CHWs from 36 municipalities participated in the study. Prevalences were 41.8% and 31.6% for anxiety and depression, respectively, while 22.5% of the group displayed symptoms of both conditions. Being female, up to 40 years old, having more than 500 users registered for monitoring, and inadequate supply of personal protective equipment were associated with anxiety and depression among the CHWs. Prevalence of anxiety and depression was high among CHWs during the pandemic and working conditions figured prominently among the associated factors.


O objetivo deste estudo foi analisar a prevalência de ansiedade e depressão associada às condições de trabalho dos agentes comunitários de saúde (ACS) no contexto da pandemia de COVID-19. Estudo transversal, realizado no norte de Minas Gerais. Foi aplicado um questionário que abordava condições sociodemográficas, domínio de tecnologias e condições de trabalho durante a pandemia, além do Inventário de Ansiedade Traço-Estado e do Patient Health Questionnare-9 (PHQ-9). Foram realizadas análises descritivas e de regressão múltipla de Poisson com variância robusta, considerando um nível de significância de 5% (p < 0,05) para o modelo final. Participaram do estudo 1.220 ACS de 36 municípios. A prevalência foi de 41,8% e 31,6% para ansiedade e depressão, respectivamente, e 22,5% para ambas as condições. O sexo feminino, idade até 40 anos, ter mais de 500 usuários cadastrados para acompanhamento e oferta inadequada de equipamentos de proteção individual estiveram associados à ansiedade e à depressão. Registrouse uma elevada prevalência de ansiedade e depressão entre ACS no período da pandemia, com destaque para as condições de trabalho entre os fatores associados.


Assuntos
COVID-19 , Humanos , Feminino , Masculino , COVID-19/epidemiologia , Pandemias , Saúde Mental , Agentes Comunitários de Saúde , Estudos Transversais , Condições de Trabalho , Depressão/epidemiologia , Depressão/psicologia , Ansiedade/epidemiologia , Ansiedade/psicologia , Pessoal de Saúde/psicologia
10.
Infect Genet Evol ; 116: 105519, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37890808

RESUMO

Invasive non-typhoidal Salmonella (iNTS) from the clonal type ST313 (S. Typhimurium ST313) is the primary cause of invasive salmonellosis in Africa. Recently, in Brazil, iNTS ST313 strains have been isolated from different sources, but there is a lack of understanding of the mechanisms behind how these gut bacteria can break the gut barrier and reach the patient's bloodstream. Here, we compare 13 strains of S. Typhimurium ST313, previously unreported isolates, from human blood cultures, investigating aspects of virulence and mechanisms of resistance. Initially, RNAseq analyses between ST13-blood isolate and SL1344 (ST19) prototype revealed 15 upregulated genes directly related to cellular invasion and replication, such as sopD2, sifB, and pipB. Limited information is available about S. Typhimurium ST313 pathogenesis and epidemiology, especially related to the global distribution of strains. Herein, the correlation of strains isolated from different sources in Brazil was employed to compare clinical and non-clinical isolates, a total of 22 genomes were studied by single nucleotide polymorphism (SNPs). The epidemiological analysis of 22 genomes of S. Typhimurium ST313 strains grouped them into three distinct clusters (A, B, and C) by SNP analysis, where cluster A comprised five, group B six, and group C 11. The 13 clinical blood isolates were all resistant to streptomycin, 92.3% of strains were resistant to ampicillin and 15.39% were resistant to kanamycin. The resistance genes acrA, acrB, mdtK, emrB, emrR, mdsA, and mdsB related to the production of efflux pumps were detected in all (100%) strains studied, similar to pathogenic traits investigated. In conclusion, we evidenced that S. Typhimurium ST313 strains isolated in Brazil have unique epidemiology. The elevated frequencies of virulence genes such as sseJ, sopD2, and pipB are a major concern in these Brazilian isolates, showing a higher pathogenic potential.


Assuntos
Infecções por Salmonella , Febre Tifoide , Humanos , Salmonella typhimurium , Aminoglicosídeos , Infecções por Salmonella/epidemiologia , Infecções por Salmonella/microbiologia , Antibacterianos/farmacologia
11.
Ciênc. Saúde Colet. (Impr.) ; 28(10): 2931-2940, out. 2023. tab, graf
Artigo em Português | LILACS-Express | LILACS | ID: biblio-1520610

RESUMO

Resumo O objetivo deste estudo foi analisar a prevalência de ansiedade e depressão associada às condições de trabalho dos agentes comunitários de saúde (ACS) no contexto da pandemia de COVID-19. Estudo transversal, realizado no norte de Minas Gerais. Foi aplicado um questionário que abordava condições sociodemográficas, domínio de tecnologias e condições de trabalho durante a pandemia, além do Inventário de Ansiedade Traço-Estado e do Patient Health Questionnare-9 (PHQ-9). Foram realizadas análises descritivas e de regressão múltipla de Poisson com variância robusta, considerando um nível de significância de 5% (p < 0,05) para o modelo final. Participaram do estudo 1.220 ACS de 36 municípios. A prevalência foi de 41,8% e 31,6% para ansiedade e depressão, respectivamente, e 22,5% para ambas as condições. O sexo feminino, idade até 40 anos, ter mais de 500 usuários cadastrados para acompanhamento e oferta inadequada de equipamentos de proteção individual estiveram associados à ansiedade e à depressão. Registrouse uma elevada prevalência de ansiedade e depressão entre ACS no período da pandemia, com destaque para as condições de trabalho entre os fatores associados.


Abstract This study examined the prevalence of anxiety and depression associated with Community Health Workers' (CHWs') working conditions in the context of the COVID-19 pandemic. This cross-sectional study was carried out in the north of Minas Gerais, Brazil by applying a questionnaire addressing sociodemographic conditions, command of technologies and working conditions during the pandemic, as well as the State-Trait Anxiety Inventory and the Patient Health Questionnare-9 (PHQ-9). Descriptive and multiple Poisson regression analyses were performed with robust variance, to a 5% level of significance (p < 0.05) for the final model. A total of 1,220 CHWs from 36 municipalities participated in the study. Prevalences were 41.8% and 31.6% for anxiety and depression, respectively, while 22.5% of the group displayed symptoms of both conditions. Being female, up to 40 years old, having more than 500 users registered for monitoring, and inadequate supply of personal protective equipment were associated with anxiety and depression among the CHWs. Prevalence of anxiety and depression was high among CHWs during the pandemic and working conditions figured prominently among the associated factors.

12.
Elife ; 122023 08 07.
Artigo em Inglês | MEDLINE | ID: mdl-37548361

RESUMO

Reactive carbonyl species (RCS) such as methylglyoxal and glyoxal are potent glycolytic intermediates that extensively damage cellular biomolecules leading to genetic aberration and protein misfolding. Hence, RCS levels are crucial indicators in the progression of various pathological diseases. Besides the glyoxalase system, emerging studies report highly conserved DJ-1 superfamily proteins as critical regulators of RCS. DJ-1 superfamily proteins, including the human DJ-1, a genetic determinant of Parkinson's disease, possess diverse physiological functions paramount for combating multiple stressors. Although S. cerevisiae retains four DJ-1 orthologs (Hsp31, Hsp32, Hsp33, and Hsp34), their physiological relevance and collective requirement remain obscure. Here, we report for the first time that the yeast DJ-1 orthologs function as novel enzymes involved in the preferential scavenge of glyoxal and methylglyoxal, toxic metabolites, and genotoxic agents. Their collective loss stimulates chronic glycation of the proteome, and nucleic acids, inducing spectrum of genetic mutations and reduced mRNA translational efficiency. Furthermore, the Hsp31 paralogs efficiently repair severely glycated macromolecules derived from carbonyl modifications. Also, their absence elevates DNA damage response, making cells vulnerable to various genotoxins. Interestingly, yeast DJ-1 orthologs preserve functional mitochondrial content, maintain ATP levels, and redistribute into mitochondria to alleviate the glycation damage of macromolecules. Together, our study uncovers a novel glycation repair pathway in S. cerevisiae and a possible neuroprotective mechanism of how hDJ-1 confers mitochondrial health during glycation toxicity.


Assuntos
Ácidos Nucleicos , Proteínas de Saccharomyces cerevisiae , Humanos , Saccharomyces cerevisiae/metabolismo , Proteínas de Choque Térmico/metabolismo , Aldeído Pirúvico/metabolismo , Reação de Maillard , Ácidos Nucleicos/metabolismo , Glioxal/metabolismo , Proteínas de Saccharomyces cerevisiae/genética , Proteínas de Saccharomyces cerevisiae/metabolismo
13.
Front Med (Lausanne) ; 10: 1198088, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37484840

RESUMO

Randomized controlled trials are considered the 'gold standard' to reduce bias by randomizing patients to an experimental intervention, versus placebo or standard of care cohort. There are inherent challenges to enrolling a standard of care or cohorts: costs, site engagement logistics, socioeconomic variability, patient willingness, ethics of placebo interventions, cannibalizing the treatment arm population, and extending study duration. The COVID-19 pandemic has magnified aspects of constraints in trial recruitment and logistics, spurring innovative approaches to reducing trial sizes, accelerating trial accrual while preserving statistical rigor. Using data from medical records and databases allows for construction of external control arms that reduce the costs of an external control arm (ECA) randomized to standard of care. Simultaneously examining covariates of the clinical outcomes in ECAs that are being measured in the interventional arm can be particularly useful in phase 2 trials to better understand social and genetic determinants of clinical outcomes that might inform pivotal trial design. The FDA and EMA have promulgated a number of publicly available guidance documents and qualification reports that inform the use of this regulatory science tool to streamline clinical development, of phase 4 surveillance, and policy aspects of clinical outcomes research. Availability and quality of real-world data (RWD) are a prevalent impediment to the use of ECAs given such data is not collected with the rigor and deliberateness that characterizes prospective interventional control arm data. Conversely, in the case of contemporary control arms, a clinical trial outcome can be compared to a contemporary standard of care in cases where the standard of care is evolving at a fast pace, such as the use of checkpoint inhibitors in cancer care. Innovative statistical methods are an essential aspect of an ECA strategy and regulatory paths for these innovative approaches have been navigated, qualified, and in some cases published.

14.
medRxiv ; 2023 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-37163081

RESUMO

Spinocerebellar ataxia type 3/Machado-Joseph disease (SCA3) is the most common autosomal dominant ataxia. In view of the development of targeted therapies for SCA3, precise knowledge of stage-dependent fluid and MRI biomarker changes is needed. We analyzed cross-sectional data of 292 SCA3 mutation carriers including 57 pre-ataxic individuals, and 108 healthy controls from the European Spinocerebellar ataxia type 3/Machado-Joseph Disease Initiative (ESMI) cohort. Blood concentrations of mutant ATXN3 and neurofilament light (NfL) were determined, and volumes of pons, cerebellar white matter (CWM) and cerebellar grey matter (CGM) were measured on MRI. Mutant ATXN3 concentrations were high before and after ataxia onset, while NfL continuously increased and deviated from normal 11.9 years before onset. Pons and CWM volumes decreased, but the deviation from normal was only 2.0 years (pons) and 0.3 years (CWM) before ataxia onset. We propose a staging model of SCA3 that includes an initial asymptomatic carrier stage followed by the biomarker stage defined by absence of ataxia, but a significant rise of NfL. The biomarker stage leads into the ataxia stage, defined by manifest ataxia. The present analysis provides a robust framework for further studies aiming at elaboration and differentiation of the staging model of SCA3.

15.
Int J Mol Sci ; 24(7)2023 Mar 24.
Artigo em Inglês | MEDLINE | ID: mdl-37047078

RESUMO

Although the exact mechanism of the pathogenesis of coronavirus SARS-CoV-2 (COVID-19) is not fully understood, oxidative stress and the release of pro-inflammatory cytokines have been highlighted as playing a vital role in the pathogenesis of the disease. In this sense, alternative treatments are needed to reduce the level of inflammation caused by COVID-19. Therefore, this study aimed to investigate the potential effect of red photobiomodulation (PBM) as an attractive therapy to downregulate the cytokine storm caused by COVID-19 in a zebrafish model. RT-qPCR analyses and protein-protein interaction prediction among SARS-CoV-2 and Danio rerio proteins showed that recombinant Spike protein (rSpike) was responsible for generating systemic inflammatory processes with significantly increased levels of pro-inflammatory (il1b, il6, tnfa, and nfkbiab), oxidative stress (romo1) and energy metabolism (slc2a1a and coa1) mRNA markers, with a pattern similar to those observed in COVID-19 cases in humans. On the other hand, PBM treatment was able to decrease the mRNA levels of these pro-inflammatory and oxidative stress markers compared with rSpike in various tissues, promoting an anti-inflammatory response. Conversely, PBM promotes cellular and tissue repair of injured tissues and significantly increases the survival rate of rSpike-inoculated individuals. Additionally, metabolomics analysis showed that the most-impacted metabolic pathways between PBM and the rSpike treated groups were related to steroid metabolism, immune system, and lipid metabolism. Together, our findings suggest that the inflammatory process is an incisive feature of COVID-19 and red PBM can be used as a novel therapeutic agent for COVID-19 by regulating the inflammatory response. Nevertheless, the need for more clinical trials remains, and there is a significant gap to overcome before clinical trials can commence.


Assuntos
COVID-19 , Animais , Humanos , Peixe-Zebra/metabolismo , SARS-CoV-2/metabolismo , Síndrome da Liberação de Citocina , Citocinas/metabolismo , RNA Mensageiro , Proteínas de Membrana , Proteínas Mitocondriais
17.
Rev. bras. cir. plást ; 38(1): 1-8, jan.mar.2023. ilus
Artigo em Inglês, Português | LILACS-Express | LILACS | ID: biblio-1428689

RESUMO

Introduction: Data mining techniques expand access to important information for the decision-making process during health care. The objective the study proposes using data mining techniques to identify variables (surgical treatment protocols, patient characteristics, post-surgical complications) associated with fistulas after primary palatoplasty in patients with unilateral transforamen incisor cleft (UTIC). Method: A data set of 222 patients with UTIC without syndromes, operated by four surgeons with Furlow's or von Langenbeck's primary palatoplasty techniques, was analyzed for this study. Two models for detecting the outcome of surgery were induced using data mining techniques (Decision Tree and Apriori). Results: Five rules were selected from a decision tree pointing to some variables as predictors of fistulas associated with primary palatoplasty: infection, cough, hypernasality, and surgeon. Analysis of the model indicates that it correctly classifies 95.9% of occurrences between the absence and presence of fistulas. The second model indicates that the absence of post-surgical complications (infection and fever) and normal speech results (absent hypernasality, without suggestive of velopharyngeal dysfunction) are related to the absence of fistulas. Regarding surgical procedures, the Furlow technique and the Vomer flap were more frequent in patients with fistulas. Conclusion: Data mining techniques, as applied in the present study, pointed to infection and cough, hypernasality, and surgeon and surgical techniques as predictors of fistulas related to primary palatoplasty.


Introdução: As técnicas de mineração de dados ampliam o acesso a informações importantes para o processo de tomada de decisão durante os cuidados com a saúde. O objetivo do estudo propõe a utilização de técnicas de mineração de dados para identificar variáveis (protocolos de tratamento cirúrgico, características do paciente, intercorrências pós-cirúrgicas) associadas à ocorrência de fístulas após palatoplastia primária em pacientes com fissura transforame incisivo unilateral (FTIU). Método: Um conjunto de dados de 222 pacientes com FTIU sem síndromes, operados por quatro cirurgiões com as técnicas de palatoplastia primária de Furlow ou von Langenbeck, foi analisado para este estudo. Dois modelos para detecção do resultado da cirurgia foram induzidos usando técnicas de mineração de dados (Árvore de Decisão e Apriori). Resultados: Cinco regras foram selecionadas de uma árvore de decisão apontando para algumas variáveis como preditivas de fístulas associadas à palatoplastia primária: infecção, tosse, hipernasalidade, cirurgião. A análise do modelo indica que ele classifica corretamente 95,9% das ocorrências entre ausência e presença de fístulas. O segundo modelo indica que a ausência de intercorrências pós-cirúrgicas (infecção e febre) e resultado de fala normal (hipernasalidade ausente, sem sugestivo de disfunção velofaríngea) estão relacionados à ausência de fístulas. Em relação aos procedimentos cirúrgicos, o uso da técnica de Furlow e retalho de Vomer foram mais frequentes nos pacientes com fístulas. Conclusão: Técnicas de mineração de dados, conforme aplicadas no presente estudo, apontaram para infecção e tosse, presença de hipernasalidade, cirurgião e técnica cirúrgica como preditores de fístulas relacionadas à palatoplastia primária.

18.
Neuropathol Appl Neurobiol ; 49(2): e12892, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-36798010

RESUMO

The European Spinocerebellar Ataxia Type 3/Machado-Joseph Disease Initiative (ESMI) is a consortium established with the ambition to set up the largest European longitudinal trial-ready cohort of Spinocerebellar Ataxia Type 3/Machado-Joseph Disease (SCA3/MJD), the most common autosomal dominantly inherited ataxia worldwide. A major focus of ESMI has been the identification of SCA3/MJD biomarkers to enable future interventional studies. As biosample collection and processing variables significantly impact the outcomes of biomarkers studies, biosampling procedures standardisation was done previously to study visit initiation. Here, we describe the ESMI consensus biosampling protocol, developed within the scope of ESMI, that ultimately might be translated to other neurodegenerative disorders, particularly ataxias, being the first step to protocol harmonisation in the field.


Assuntos
Ataxia Cerebelar , Doença de Machado-Joseph , Ataxias Espinocerebelares , Degenerações Espinocerebelares , Humanos , Biomarcadores
19.
J Cell Sci ; 136(2)2023 01 15.
Artigo em Inglês | MEDLINE | ID: mdl-36601773

RESUMO

TIM22 pathway cargos are essential for sustaining mitochondrial homeostasis as an excess of these proteins leads to proteostatic stress and cell death. Yme1 is an inner membrane metalloprotease that regulates protein quality control with chaperone-like and proteolytic activities. Although the mitochondrial translocase and protease machinery are critical for organelle health, their functional association remains unexplored. The present study unravels a novel genetic connection between the TIM22 complex and YME1 machinery in Saccharomyces cerevisiae that is required for maintaining mitochondrial health. Our genetic analyses indicate that impairment in the TIM22 complex rescues the respiratory growth defects of cells without Yme1. Furthermore, Yme1 is essential for the stability of the TIM22 complex and regulates the proteostasis of TIM22 pathway substrates. Moreover, impairment in the TIM22 complex suppressed the mitochondrial structural and functional defects of Yme1-devoid cells. In summary, excessive levels of TIM22 pathway substrates could be one of the reasons for respiratory growth defects of cells lacking Yme1, and compromising the TIM22 complex can compensate for the imbalance in mitochondrial proteostasis caused by the loss of Yme1.


Assuntos
Proteínas de Transporte da Membrana Mitocondrial , Proteínas de Saccharomyces cerevisiae , Proteínas de Transporte da Membrana Mitocondrial/genética , Proteínas de Transporte da Membrana Mitocondrial/metabolismo , Proteostase , Proteínas do Complexo de Importação de Proteína Precursora Mitocondrial , Proteínas de Saccharomyces cerevisiae/metabolismo , Mitocôndrias/metabolismo , Saccharomyces cerevisiae/metabolismo , Proteínas Mitocondriais/genética , Proteínas Mitocondriais/metabolismo , Proteases Dependentes de ATP
20.
Food Sci Technol Int ; : 10820132231153496, 2023 Jan 26.
Artigo em Inglês | MEDLINE | ID: mdl-36703262

RESUMO

Chitosan nanocapsules containing polyunsaturated fatty acid (PUFA) concentrates from tuna oil, with EPA + DHA contents around 57% (w w-1), were developed by emulsification process, using different chitosan concentration (1.0%, 1.5%, 2.0%, w v-1) and stirring speed (10,000, 15,000, 20,000 rpm). The effects of these parameters on particle size and zeta potential were evaluated. The physical and oxidative stabilities were used to measure the product quality during storage. Chitosan concentration, stirring speed and its interaction significantly affected (p < 0.05) the particle size. In addition, chitosan concentration significantly affected (p < 0.05) the zeta potential of nanocapsules emulsion. Based on the results of physical and oxidative stabilities, the nanocapsules were stable for 30 days under refrigeration temperature (7 °C), and with 1.5-2% chitosan resulted in improved protection against oil oxidation. The nanocapsules produced with 2% chitosan and 10,000 rpm showed the lowest variations of polydispersity index and nanocapsules size after 30 days of storage (221.8 ± 3.0 nm). These conditions can be considered the most suitable to produce nanocapsules of PUFA concentrates from tuna oil using chitosan as wall material. These nanocapsules showed physical characteristics and oxidative stability, which could enable their application in the food industry, representing an important source of EPA and DHA fatty acids.

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