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La presente investigación pretende evaluar el nivel de cumplimiento de las metas internacionales, que representan el foco principal para la mejora de calidad y seguridad de atención de los pacientes. La seguridad del paciente involucra a todos los estudios, prácticas y acciones promovidas por las instituciones sanitarias para disminuir y eliminar los riesgos de daños innecesarios relacionados con el cuidado de la salud. Metodología: Estudio descriptivo, observacional y transversal. De fuentes primaria y secundaria, Resultados: se abordaron las metas N° 1 la cual consiste en Identificar a los pacientes correctamente y la meta N° 6 la cual se refiere a Reducir el riesgo de lesiones en pacientes como resultado de caídas. En primer lugar, se destaca el cumplimiento en la identificación correcta del paciente y en segunda instancia la mejora del cumplimiento de medidas de prevención de caídas. Conclusión: Esta proximidad de los valores obtenidos genera un aspecto positivo para mejorar la seguridad de los pacientes y que, si bien el cumplimiento de las metas no es el deseado, es cercano al porcentaje planteado. Lo que en definitiva hace a este estudio un antecedente importante en la mejora continua con vista al futuro cercano[AU]
This research aims to evaluate the level of compliance with international goals, which represent the main focus for improving the quality and safety of patient care. Patient safety involves all studies, practices and actions promoted by health institutions to reduce and eliminate the risks of unnecessary harm related to health care. Methodology: Descriptive, observational and transversal study. From primary and secondary sources, Results: goals No. 1 were addressed, which consists of Identifying patients correctly and goal No. 6, which refers to Reducing the risk of injuries in patients as a result of falls. Firstly, compliance with correct patient identification stands out and secondly, improvement in compliance with fall prevention measures. Conclusion: This proximity of the values obtained generates a positive aspect to improve patient safety and that, although the fulfillment of the goals is not as desired, it is close to the proposed percentage. Which ultimately makes this study an important precedent in continuous improvement for the near future[AU]
Esta pesquisa tem como objetivo avaliar o nível de cumprimento das metas internacionais, que representam o foco principal para a melhoria da qualidade e segurança do atendimento ao paciente. A segurança do paciente envolve todos os estudos, e ações promovidas pelas instituições de saúde para reduzir e eliminar os riscos de danos desnecessários relacionados à assistência à saúde. Metodologia: Estudo descritivo, observacional e transversal. De fontes primárias e secundárias, dependendo do indicador e do objetivo para o qual a medição está sendo realizada. Resultados: Nesta pesquisa serão abordadas as metas nº1, que consiste em Identificar corretamente os pacientes e a meta nº 6, que es Reduzir o risco de lesões nos pacientes em decorrência de quedas. Foi realizado nos dois locais. Em primeiro lugar, destaca-se o cumprimento da correta identificação do paciente e, em segundo lugar, a melhoria no cumprimento das medidas de prevenção de quedas. Conclusão: Essa proximidade dos valores obtidos gera um aspecto positivo para melhorar a segurança do paciente e que, embora o cumprimento das metas não seja o desejado, está próximo do percentual proposto. O que acaba por tornar este estudo um precedente importante na melhoria contínua com vista ao futuro próximo.
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Humanos , Sistemas de Identificação de Pacientes , Qualidade da Assistência à Saúde , Acidentes por Quedas/prevenção & controleRESUMO
The common bean (Phaseolus vulgaris L.) is a crucial legume crop and an ideal evolutionary model to study adaptive diversity in wild and domesticated populations. Here, we present a common bean pan-genome based on five high-quality genomes and whole-genome reads representing 339 genotypes. It reveals ~234 Mb of additional sequences containing 6,905 protein-coding genes missing from the reference, constituting 49% of all presence/absence variants (PAVs). More non-synonymous mutations are found in PAVs than core genes, probably reflecting the lower effective population size of PAVs and fitness advantages due to the purging effect of gene loss. Our results suggest pan-genome shrinkage occurred during wild range expansion. Selection signatures provide evidence that partial or complete gene loss was a key adaptive genetic change in common bean populations with major implications for plant adaptation. The pan-genome is a valuable resource for food legume research and breeding for climate change mitigation and sustainable agriculture.
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Domesticação , Genoma de Planta , Phaseolus , Phaseolus/genética , Adaptação Fisiológica/genética , Genótipo , Variação Genética , Produtos Agrícolas/genética , Seleção Genética , Evolução Molecular , Mutação , Melhoramento Vegetal/métodosRESUMO
PURPOSE: The objective of this prospective, single-centre case series was to investigate feasibility, clinical outcomes, and neural correlates of non-invasive Neuromodulation-Induced Cortical Prehabilitation (NICP) before brain tumor surgery. Previous studies have shown that gross total resection is paramount to increase life expectancy but is counterbalanced by the need of preserving critical functional areas. NICP aims at expanding functional margins for extensive tumor resection without functional sequelae. Invasive NICP (intracranial neuromodulation) was effective but characterized by elevated costs and high rate of adverse events. Non-invasive NICP (transcranial neuromodulation) may represent a more feasible alternative. Nonetheless, up to this point, non-invasive NICP has been examined in only two case reports, yielding inconclusive findings. METHODS: Treatment sessions consisted of non-invasive neuromodulation, to transiently deactivate critical areas adjacent to the lesion, coupled with intensive functional training, to activate alternative nodes within the same functional network. Patients were evaluated pre-NICP, post-NICP, and at follow-up post-surgery. RESULTS: Ten patients performed the intervention. Feasibility criteria were met (retention, adherence, safety, and patient's satisfaction). Clinical outcomes showed overall stability and improvements in motor and executive function from pre- to post-NICP, and at follow-up. Relevant plasticity changes (increase in the distance between tumor and critical area) were observed when the neuromodulation target was guided by functional neuroimaging data. CONCLUSION: This is the first case series demonstrating feasibility of non-invasive NICP. Neural correlates indicate that neuroimaging-guided target selection may represent a valid strategy to leverage neuroplastic changes before neurosurgery. Further investigations are needed to confirm such preliminary findings.
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A 40-year-old male with a history of human immunodeficiency virus (HIV) (CD4 absolute count 57 cells/uL) presented to the Emergency Department complaining of large, swollen abscesses on his face, right hand, and feet. He reported the outbreak of the lesions occurred four months ago and coincided with a week-long episode of diarrhea, rectal pain, and perirectal and inguinal lymphadenopathy. Physical exam was significant for a full-thickness fluid collection on the sole of the right foot, a plantar abscess on the left foot, an open, crusted ulcer on the left fifth finger, and several large, crusted lesions on the face. Of note, the patient was seen at a nearby hospital three months prior, underwent a biopsy that showed non-variola orthopoxvirus DNA via real-time polymerase chain reaction (PCR), and was diagnosed with monkeypox at that time. He was advised to pick up tecovirimat treatment from the Department of Health but stated it was unavailable when he arrived and never took it. On this admission, the lesion was again biopsied and detected non-variola orthopoxvirus DNA by real-time PCR. The patient was discharged on 600 mg tecovirimat orally twice daily for 14 days. At the 14-day follow-up, the patient's lesions had completely fallen off and were no longer painful.
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INTRODUCTION: Current literature lacks consensus on initial assessments and routine follow-up care of patients with alpha-mannosidosis (AM). A Delphi panel was conducted to generate and validate recommendations on best practices for initial assessment, routine follow-up care, and integrated care coordination of patients with AM. METHODS: A modified Delphi method involving 3 rounds of online surveys was used. An independent administrator and 2 nonvoting physician co-chairs managed survey development, anonymous data collection, and analysis. A multidisciplinary panel comprising 20 physicians from 12 countries responded to 57 open-ended questions in the first survey. Round 2 consisted of 11 ranking questions and 44 voting statements. In round 3, panelists voted to validate 60 consensus statements. The panel response rate was ≥95% in all 3 rounds. Panelists used 5-point Likert scales to indicate importance (score of ≥3) or agreement (score of ≥4). Consensus was defined a priori as ≥75% agreement with ≥75% of panelists voting. RESULTS: Consensus was reached on 60 statements, encompassing 3 key areas: initial assessments, routine follow-up care, and treatment-related follow-up. The panel agreed on the type and frequency of assessments related to genetic testing, baseline evaluations, quality of life, biochemical measures, affected body systems, treatment received, and integrated care coordination in patients with AM. Forty-nine statements reached 90% to 100% consensus, 8 statements reached 80% to 85% consensus, and 1 statement reached 75% consensus. Two statements each reached consensus on 15 baseline assessments to be conducted at the initial follow-up visit after diagnosis in pediatric and adult patients. CONCLUSION: This is the first Delphi study providing internationally applicable, best-practice recommendations for monitoring patients with AM that may improve their care and well-being.
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Consenso , Técnica Delphi , alfa-Manosidose , Humanos , alfa-Manosidose/terapia , alfa-Manosidose/diagnóstico , Inquéritos e Questionários , Prestação Integrada de Cuidados de Saúde/normasRESUMO
Introduction: Provider bias against patients of higher weights can contribute to poor health outcomes and decreased quality of care and patient experience. Addressing weight stigma in sexual and reproductive health settings is important, as these encounters can often be patients' only health care touchpoint. Health care providers must be educated about the harms of weight stigma, ways to recognize and confront their biases, and how to advocate for patients of all sizes. Methods: In this quality improvement project, Planned Parenthood health center providers participated in a three-part virtual workshop to improve provider weight bias awareness and understanding using the Health at Every Size framework. Providers completed a pre- and post-survey, as well as a 3-month follow-up survey to assess changes in bias awareness and confidence in applying weight-neutral principles in care interactions. Results: Analysis of pre- and post-survey results showed significant improvements in provider awareness of bias as well as changes in implicit bias scores and confidence providing weight-neutral care. Conclusion: Educating providers about weight contributes to equity of care for patients of higher weights. Formal education such as workshops have the potential to reduce the harms of weight stigma in health care as changing attitudes and confidence are a precursor to behavior change. Research is needed to assess ideal education modalities and whether receiving care from weight bias-prepared providers affects patient outcomes and experiences.
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Covered anaerobic lagoons (CALs) are Latin America's main livestock waste treatment systems. Mexico has 680 CALs that present low biogas yields (0.05 m3 m-3 digester d-1) and low COD removal rates (< 60%). This work focused on diagnosing CAL´s low performance in dairy farms by determining and analyzing operational parameters. Seven CALs located in the main dairy basin of Mexico were analyzed. The sampling areas for each CAL were the supernatant, the active zone, settled sludge, and digester inlet and outlet. The variation of the process parameter values corroborated that CALs appeared stratified and not working as expected. The sludge zone, comprising 50-58% of total solids content and 1-15% of total CALs volume, showed an elemental compounds content suitable for organic fertilizer (340, 48, and 5 kg t-1 of C, N, and S, respectively). However, this zone contained, at least, 85% of the slowly hydrolysable material; the methanogenic potential was less than 87 mL CH4 g VS-1, and the C/N ratio ranged from 4.9 to 17, outside of the optimal range. The biogas produced did not exceed 60% of methane content and more than 3000 ppm of H2S. The sludge zone significantly influences the lagoon's dynamics since it is a nutrient sink. Furthermore, the lack of agitation is the leading cause for the low energy yield and the low removal of organic matter rate. This work provides valuable information to address the operational problems within the CALs improving our understanding that shall allow proposing reactivation alternatives.
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Several studies indicate that some cognitive changes occur after COVID-19. Visuospatial alterations have been reported in 24-40â¯%. These alterations may be useful as early biomarkers of neurodegenerative disease. Thus, we can emphasize the importance of visuospatial processes in cognition through quantitative and qualitative analysis of performance on the Clock Test (CDT) and the Rey-Osterrieth Complex Figure (FCRO). Our objective was to describe the performance of post COVID 19 patients in visuospatial tests, with different degrees of respiratory impairment and to perform a qualitative analysis of the performance to check its relationship with alterations in attention and executive functions. This will allow highlighting the executive component of the performance of the CDT and ROCF and differentiate patients with possible cognitive impairment. 77 patients with SARS-CoV-2 infection were evaluated (3 months post-infection) with a complete neuropsychological battery and MRI. Overall, there is a significant difference between FCRO and CDT, with FCRO having only 9â¯% change and CDT having 51.9â¯% change. Regarding the correlations observed between groups (VM Inv, VM non I and non hospitalized) the highest correlations were observed between Boston with FCRO copy (r=0.497; p=0.001) and with FCRO memory (r=0.429; p=0.001). Comparing the performance between groups by severity, significant differences were observed only in the TMT A (13.706 p=0.001) and B (9.583 p=0.008) tests and in the phonological fluency letter A (13.445 p=0.001), we observed that the group of non-hospitalized patients had a better performance. Neuropsychological deficits often have a direct impact on daily life by affecting the ability to learn and adapt. Thus, a useful strategy for the neuropsychological characterization of post-COVID-19 patients is the qualitative analysis of visuospatial abilities in conjunction with executive functions that cannot be analyzed in isolation.
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COVID-19 , Disfunção Cognitiva , Função Executiva , Testes Neuropsicológicos , Humanos , COVID-19/complicações , Masculino , Feminino , Pessoa de Meia-Idade , Função Executiva/fisiologia , Disfunção Cognitiva/etiologia , Disfunção Cognitiva/fisiopatologia , Idoso , Percepção Espacial/fisiologia , SARS-CoV-2 , Adulto , Atenção/fisiologia , Imageamento por Ressonância Magnética , Percepção Visual/fisiologia , Cognição/fisiologiaRESUMO
Colorectal cancer (CRC) remains one of the most commonly diagnosed and deadliest types of cancer worldwide. CRC displays a desmoplastic reaction (DR) that has been inversely associated with poor prognosis; less DR is associated with a better prognosis. This reaction generates excessive connective tissue, in which cancer-associated fibroblasts (CAFs) are critical cells that form a part of the tumor microenvironment. CAFs are directly involved in tumorigenesis through different mechanisms. However, their role in immunosuppression in CRC is not well understood, and the precise role of signal transducers and activators of transcription (STATs) in mediating CAF activity in CRC remains unclear. Among the myriad chemical and biological factors that affect CAFs, different cytokines mediate their function by activating STAT signaling pathways. Thus, the harmful effects of CAFs in favoring tumor growth and invasion may be modulated using STAT inhibitors. Here, we analyze the impact of different STATs on CAF activity and their immunoregulatory role.
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Colorectal cancer (CRC) is one of the most prevalent fatal neoplasias worldwide. Despite efforts to improve the early diagnosis of CRC, the mortality rate of patients is still nearly 50%. The primary treatment strategy for CRC is surgery, which may be accompanied by chemotherapy and radiotherapy. The conventional and first-line chemotherapeutic agent utilized is 5-fluorouracil (5FU). However, it has low efficiency. Combination treatment with leucovorin and oxaliplatin or irinotecan improves the effectiveness of 5FU therapy. Unfortunately, most patients develop drug resistance, leading to disease progression. Here, we evaluated the effect of a potential alternative adjuvant treatment for 5FU, helminth-derived Taenia crassiceps (TcES) molecules, on treating advanced colitis-associated colon cancer. The use of TcES enhanced the effects of 5FU on established colonic tumors by downregulating the expression of the immunoregulatory cytokines, Il-10 and Tgf-ß, and proinflammatory cytokines, Tnf-α and Il-17a, and reducing the levels of molecular markers associated with malignancy, cyclin D1, and Ki67, both involved in apoptosis inhibition and the signaling pathway of ß-catenin. TcES+5FU therapy promoted NK cell recruitment and the release of Granzyme B1 at the tumor site, consequently inducing tumor cell death. Additionally, it restored P53 activity which relates to decreased Mdm2 expression. In vitro assays with human colon cancer cell lines showed that therapy with TcES+5FU significantly reduced cell proliferation and migration by modulating the P53 and P21 signaling pathways. Our findings demonstrate, for the first time in vivo, that helminth-derived excreted/secreted products may potentiate the effect of 5FU on established colon tumors.
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Fluoruracila , Animais , Fluoruracila/farmacologia , Fluoruracila/uso terapêutico , Taenia/efeitos dos fármacos , Neoplasias do Colo/tratamento farmacológico , Neoplasias do Colo/patologia , Apoptose/efeitos dos fármacos , Citocinas/metabolismo , Camundongos , Humanos , Linhagem Celular Tumoral , Carcinogênese/efeitos dos fármacos , Granzimas/metabolismo , Proliferação de Células/efeitos dos fármacos , Camundongos Endogâmicos BALB CRESUMO
BACKGROUND: Neuroblastoma is a common pediatric malignancy with poor survival for high-risk disease. Mesenchymal stromal cells (MSCs) have innate tumor-homing properties, enabling them to serve as a cellular delivery vehicle, but MSCs have demonstrated variable effects on tumor growth. We compared how placental MSCs (PMSCs) and bone marrow-derived MSCs (BM-MSCs) affect proliferation of neuroblastoma (NB) cells in vitro. METHODS: Indirect co-culture assessed proliferative effects of 18 MSCs (early-gestation PMSCs (n = 9), term PMSCs (n = 5), BM-MSCs (n = 4) on three high-risk NB cell lines (NB1643, SH-SY5Y, and CHLA90). Controls were NB cells cultured in media alone. Proliferation was assessed using MTS assay and measured by fold change (fc) over controls. PMSCs were sub-grouped by neuroprotective effect: strong (n = 7), intermediate (n = 3), and weak (n = 4). The relationship between MSC type, PMSC neuroprotection, and PMSC gestational age on NB cell proliferation was assessed. RESULTS: NB cell proliferation varied between MSC groups. BM-MSCs demonstrated lower proliferative effects than PMSCs (fc 1.18 vs 1.44, p < 0.001). Neither gestational age nor neuroprotection significantly predicted degree of proliferation. Proliferative effects of MSCs varied among NB cell lines. BM-MSCs had less effect on CHLA90 (fc 1.01) compared to NB1643 (fc 1.33) and SH-SY5Y (fc 1.20). Only NB1643 showed a difference between early and term PMSCs (p = 0.04). CONCLUSION: Effects of MSCs on NB cell proliferation vary by MSC source and NB cell line. BM-MSCs demonstrated lower proliferative effects than most PMSCs. MSC neuroprotection was not correlated with proliferation. Improved understanding of MSC proliferation-promoting mechanisms may provide valuable insight into selection of cells best suited as drug delivery vehicles. LEVEL OF EVIDENCE: N/A. TYPE OF STUDY: Original Research.
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Proliferação de Células , Técnicas de Cocultura , Células-Tronco Mesenquimais , Neuroblastoma , Placenta , Humanos , Neuroblastoma/patologia , Linhagem Celular Tumoral , Feminino , Placenta/citologia , Gravidez , Células da Medula Óssea , Idade GestacionalRESUMO
Background: Osteoarthritis is a frequent rheumatic disease. Some single-nucleotide polymorphisms of the gene associated with fat mass and obesity are associated with increased body mass index and knee osteoarthritis. Objective: The objective of this study was to analyze the association of single nucleotide polymorphism rs1477196 of the fat mass and obesity gene with primary knee osteoarthritis. Methods: This observational and cross-sectional study included 347 Mexican participants. We performed the genotypification analysis with TaqMan® probe C_2031262_10 for rs1477196 (Thermo Fisher Scientific). Multivariate analysis included covariables such as age, type 2 diabetes, obesity, and postmenopause. Results: Type 2 diabetes, obesity, and postmenopause were associated with primary knee osteoarthritis in female participants. We did not find an association between rs1477196 and obesity. In the codominant and dominant genetic models, rs1477196 was significantly associated with primary knee osteoarthritis only in the female group, including in the model adjusted by other covariables (odds ratio = 2.517; 1.035-6.123; p = 0.042 and odds ratio = 2.387; 1.054-5.407; p = 0.037, respectively). The interaction between rs1477196 and obesity was significantly associated with primary knee osteoarthritis in female participants (p = 0.039 and p = 0.043). Conclusions: Our findings suggest that the rs1477196 variant of the fat and obesity mass gene may be associated with the risk of primary knee osteoarthritis in women.
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Dioxigenase FTO Dependente de alfa-Cetoglutarato , Diabetes Mellitus Tipo 2 , Osteoartrite do Joelho , Feminino , Humanos , Dioxigenase FTO Dependente de alfa-Cetoglutarato/genética , Estudos Transversais , México , Obesidade/epidemiologia , Obesidade/genética , Osteoartrite do Joelho/epidemiologia , Osteoartrite do Joelho/genética , Polimorfismo de Nucleotídeo ÚnicoRESUMO
BACKGROUND/AIM: Neuroblastoma is a common childhood cancer with poor survival for children with high-risk disease, and ongoing research to improve outcomes is needed. Patient-derived xenografts (PDX) and genetically engineered mouse models (GEMM) are reliable models for oncologic research; however, they are resource-intensive, expensive, and require significant expertise to develop and maintain. We developed an orthotopic xenograft murine model of neuroblastoma that utilizes cryopreserved banks of human neuroblastoma cell lines, requires minimal equipment, and is easily reproducible. MATERIALS AND METHODS: The neuroblastoma cell line NB1643 was obtained from the Children's Oncology Group (COG) Childhood Cancer Repository. Nod-SCID-gamma (NSG) mice underwent orthotopic injection of 2x106 NB1643 cells suspended in 10 µl of collagen hydrogel directly into the adrenal gland via an open retroperitoneal surgical approach. Mice were monitored by ultrasound and in vivo imaging system (IVIS) until the tumor reached the volume of the ipsilateral kidney. Tumor identity was confirmed by necropsy and histologic analysis. RESULTS: A total of 55 mice underwent surgery. Eight died due to anesthetic or surgical complications. 39/47 (78%) survivors grew primary adrenal tumors. Average anesthesia time was 30 min. Ultrasound and IVIS successfully characterized tumor growth in all mice. Average time to target tumor size was 5 weeks (range=3-9). Gross pathologic and histologic analysis confirmed adrenal tumors consistent with neuroblastoma in all mice with adrenal masses. CONCLUSION: A cell-derived orthotopic xenograft murine model can be successfully used to create an in vivo model of neuroblastoma. This model can be utilized in environments where PDX or GEMM models are not feasible.
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Neoplasias das Glândulas Suprarrenais , Neuroblastoma , Criança , Humanos , Animais , Camundongos , Modelos Animais de Doenças , Xenoenxertos , Camundongos SCID , Neuroblastoma/genética , Neuroblastoma/patologia , Neoplasias das Glândulas Suprarrenais/patologia , Ensaios Antitumorais Modelo de Xenoenxerto , Linhagem Celular TumoralRESUMO
Fabry disease (FD) is a X-linked rare lysosomal storage disorder caused by deficient α-galactosidase A (α-GalA) activity. Early diagnosis and the prediction of disease course are complicated by the clinical heterogeneity of FD, as well as by the frequently inconclusive biochemical and genetic test results that do not correlate with clinical course. We sought to identify potential biomarkers of FD to better understand the underlying pathophysiology and clinical phenotypes. We compared the plasma proteomes of 50 FD patients and 50 matched healthy controls using DDA and SWATH-MS. The >30 proteins that were differentially expressed between the 2 groups included proteins implicated in processes such as inflammation, heme and haemoglobin metabolism, oxidative stress, coagulation, complement cascade, glucose and lipid metabolism, and glycocalyx formation. Stratification by sex revealed that certain proteins were differentially expressed in a sex-dependent manner. Apolipoprotein A-IV was upregulated in FD patients with complications, especially those with chronic kidney disease, and apolipoprotein C-III and fetuin-A were identified as possible markers of FD with left ventricular hypertrophy. All these proteins had a greater capacity to identify the presence of complications in FD patients than lyso-GB3, with apolipoprotein A-IV standing out as being more sensitive and effective in differentiating the presence and absence of chronic kidney disease in FD patients than renal markers such as creatinine, glomerular filtration rate and microalbuminuria. Identification of these potential biomarkers can help further our understanding of the pathophysiological processes that underlie the heterogeneous clinical manifestations associated with FD.
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Biomarcadores , Doença de Fabry , Fenótipo , Proteômica , Humanos , Doença de Fabry/sangue , Masculino , Feminino , Biomarcadores/sangue , Adulto , Pessoa de Meia-Idade , Estudos de Casos e Controles , Caracteres Sexuais , Adulto Jovem , Proteoma/metabolismoRESUMO
The high failure rate of central nervous system (CNS) drugs is partly associated with an insufficient understanding of target site exposure. Blood-brain barrier (BBB) permeability evaluation tools are needed to explore drugs' ability to access the CNS. An outstanding aspect of physiologically based pharmacokinetic (PBPK) models is the integration of knowledge on drug-specific and system-specific characteristics, allowing the identification of the relevant factors involved in target site distribution. We aimed to qualify a PBPK platform model to be used as a tool to predict CNS concentrations when significant transporter activity is absent and human data are sparse or unavailable. Data from the literature on the plasma and CNS of rats and humans regarding acetaminophen, oxycodone, lacosamide, ibuprofen, and levetiracetam were collected. Human BBB permeability values were extrapolated from rats using inter-species differences in BBB surface area. The percentage of predicted AUC and Cmax within the 1.25-fold criterion was 85% and 100% for rats and humans, respectively, with an overall GMFE of <1.25 in all cases. This work demonstrated the successful application of the PBPK platform for predicting human CNS concentrations of drugs passively crossing the BBB. Future applications include the selection of promising CNS drug candidates and the evaluation of new posologies for existing drugs.
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ABSTRACT Background: Osteoarthritis is a frequent rheumatic disease. Some single-nucleotide polymorphisms of the gene associated with fat mass and obesity are associated with increased body mass index and knee osteoarthritis. Objective: The objective of this study was to analyze the association of single nucleotide polymorphism rs1477196 of the fat mass and obesity gene with primary knee osteoarthritis. Methods: This observational and cross-sectional study included 347 Mexican participants. We performed the genotypification analysis with TaqMan® probe C_2031262_10 for rs1477196 (Thermo Fisher Scientific). Multivariate analysis included covariables such as age, type 2 diabetes, obesity, and postmenopause. Results: Type 2 diabetes, obesity, and postmenopause were associated with primary knee osteoarthritis in female participants. We did not find an association between rs1477196 and obesity. In the codominant and dominant genetic models, rs1477196 was significantly associated with primary knee osteoarthritis only in the female group, including in the model adjusted by other covariables (odds ratio = 2.517; 1.035-6.123; p = 0.042 and odds ratio = 2.387; 1.054-5.407; p = 0.037, respectively). The interaction between rs1477196 and obesity was significantly associated with primary knee osteoarthritis in female participants (p = 0.039 and p = 0.043). Conclusions: Our findings suggest that the rs1477196 variant of the fat and obesity mass gene may be associated with the risk of primary knee osteoarthritis in women.
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BACKGROUND: COVID-19 is a disease known for its neurological involvement. SARS-CoV-2 infection triggers neuroinflammation, which could significantly contribute to the development of long-term neurological symptoms and structural alterations in the gray matter. However, the existence of a consistent pattern of cerebral atrophy remains uncertain. OBJECTIVE: Our study aimed to identify patterns of brain involvement in recovered COVID-19 patients and explore potential relationships with clinical variables during hospitalization. METHODOLOGY: In this study, we included 39 recovered patients and 39 controls from a pre-pandemic database to ensure their non-exposure to the virus. We obtained clinical data of the patients during hospitalization, and 3 months later; in addition we obtained T1-weighted magnetic resonance images and performed standard screening cognitive tests. RESULTS: We identified two groups of recovered patients based on a cluster analysis of the significant cortical thickness differences between patients and controls. Group 1 displayed significant cortical thickness differences in specific cerebral regions, while Group 2 exhibited significant differences in the cerebellum, though neither group showed cognitive deterioration at the group level. Notably, Group 1 showed a tendency of higher D-dimer values during hospitalization compared to Group 2, prior to p-value correction. CONCLUSION: This data-driven division into two groups based on the brain structural differences, and the possible link to D-dimer values may provide insights into the underlying mechanisms of SARS-COV-2 neurological disruption and its impact on the brain during and after recovery from the disease.
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COVID-19 , Humanos , COVID-19/complicações , COVID-19/patologia , SARS-CoV-2 , Encéfalo/diagnóstico por imagem , Cerebelo/patologia , Análise por ConglomeradosRESUMO
OBJECTIVE: The present study was designed to investigate the role of macrophage migration inhibitory factor (MIF) in the exacerbation of pregestational periodontal disease (PGPD). BACKGROUND: Periodontitis (PT) is a severe stage of periodontal disease characterized by inflammation of the supporting tissues of the teeth, which usually worsens during pregnancy. MIF is a proinflammatory cytokine that is significantly elevated in periodontitis, both at the beginning and at the end of pregnancy. Although periodontitis usually presents with greater severity during pregnancy, the participation of MIF in the evolution of periodontitis has not been established. METHODS: To analyze the relevance of MIF in the exacerbation of PGPD, we employed a model of PGPD in WT and Mif-/- mice, both with a BALB/c genetic background. PT was induced with nylon suture ligatures placed supramarginally around the second upper right molar. For PGPD, PT was induced 2 weeks before mating. We evaluated histological changes and performed histometric analysis of the clinical attachment loss, relative expression of MMP-2 and MMP-13 by immunofluorescence, and relative expression of the cytokines mif, tnf-α, ifn-γ, and il-17 by quantitative real-time polymerase chain reaction (qRT-PCR). RESULTS: Our data revealed that periodontal tissue from PGPD WT mice produced a twofold increase in MIF compared with PT WT mice. Moreover, the evolution of periodontitis in Mif-/- mice was less severe than in PGDP WT mice. Periodontal tissue from Mif-/- mice with PGPD produced 80% less TNF-α and no IFN-γ, as well as 50% lower expression of matrix metalloproteinase (MMP)-2 and 25% less MMP-13 compared to WT PGDP mice. CONCLUSIONS: Our study suggests that MIF plays an important role in the exacerbation of periodontitis during pregnancy and that MIF is partially responsible for the inflammation associated with the severity of periodontitis during pregnancy.
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Fatores Inibidores da Migração de Macrófagos , Periodontite , Animais , Feminino , Camundongos , Gravidez , Inflamação/metabolismo , Fatores Inibidores da Migração de Macrófagos/metabolismo , Metaloproteinase 13 da Matriz , Periodontite/metabolismo , Fator de Necrose Tumoral alfaRESUMO
PURPOSE: To evaluate the self-reported perspectives of participants involved in the Previene Cádiz intervention for preventing pediatric overweight and obesity. DESIGN AND METHODS: This qualitative study collected information through the World Café technique. A purposive sample of 40 participants was used, of which 14 were schoolchildren, 12 were teachers, and 14 were parent volunteers. The data were segmented, and concepts were created and grouped into dimensions and categories. RESULTS: The participants confirmed they had learned new information and behaviors about healthy habits. Parental awareness was considered a crucial and necessary element in changing family habits; therefore, increasing the motivation of family members was deemed a critical task in public health interventions conducted in school settings. DISCUSSION: Despite the suitability of qualitative methodology to evaluate the perceptions of the main players in an educational intervention, scientific literature is scarce. Obtaining information from the educational community about an intervention is not always easy, so the perspectives of teachers, students, and families about the Previene Cádiz intervention through the World Café approach is considered a relevant contribution. CONCLUSIONS: The participants considered the intervention positive in terms of learning and fostering increased knowledge, awareness, and healthy behaviors. PRACTICE IMPLICATIONS: Future interventions should encourage the active participation of all social groups involved, integrating dynamic and collaborative training activities that are acceptable to all participants.
Assuntos
Sobrepeso , Obesidade Infantil , Criança , Humanos , Sobrepeso/prevenção & controle , Obesidade/prevenção & controle , Comportamentos Relacionados com a Saúde , Família , Pesquisa Qualitativa , Obesidade Infantil/prevenção & controleRESUMO
The conservation and characterization of landraces have key roles in the safeguarding and valorization of agrobiodiversity. Indeed, these plant genetic resources represent an important crop heritage with quality and sensory characteristics that can be of great use to consumers and industry. In addition, the preservation of genetic resources from the risk of progressive genetic erosion, and the enhancement of their potential can contribute to food security and improve the nutritional value of food. Accordingly, this study aimed to investigate a collection of Sardinian tomato landraces for parameters that have determinant roles in evaluating their responses to conservation, and therefore to consumer acceptance. Six Sardinian landraces and two commercial varieties were cultivated in a two-years off-season trial, harvested at two different maturity stages (turning, red-ripe) and characterized using 14 fruit-related quality parameters that define the marketability, nutritional value, and flavor of the fruit. Data were collected at intervals of 10 days, starting from the harvest date and over 30 days of storage under refrigeration. The simultaneous analysis of all the qualitative characteristics for the different genotypes allowed to clearly differentiate the local varieties from the commercial varieties and a few landraces emerged for their satisfactory performances, e.g. "Tamatta kaki" ad "Tamatta groga de appiccai". In particular, the "Tamatta groga de appiccai" showed satisfactory lycopene content at marketable stages (average 5.65 mg 100g-1 FF), a peculiar orange-pink color with the highest hue angle values (range: H°T0 = 72.55-H°T30 = 48.26), and the highest firmness among the landraces of the red-ripe group (range: EpT0 = 1.64-EpT30 = 0.54 N mm-1). These results highlight the potential of some of the Sardinian tomato landraces for developing new varieties or promoting their direct valorization in local markets and could considerably increase the effectiveness and efficiency of agrobiodiversity conservation strategies.