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1.
Arq Bras Cardiol ; 121(4): e20230544, 2024.
Artigo em Português, Inglês | MEDLINE | ID: mdl-38695471

RESUMO

BACKGROUND: Ablation Index (AI) software has allowed better atrial fibrillation (AF) ablation results, but recurrence rates remain significant. Specific serum biomarkers have been associated with this recurrence. OBJECTIVES: To evaluate whether certain biomarkers could be used (either individually or combined) to predict arrhythmia recurrence after AI-guided AF ablation. METHODS: Prospective multicenter observational study of consecutive patients referred for AF ablation from January 2018 to March 2021. Hemoglobin, brain natriuretic peptide (BNP), C-reactive protein, high sensitivity cardiac troponin I, creatinine clearance, thyroid-stimulating hormone (TSH) and free thyroxine (FT4) were assessed for their ability to predict arrhythmia recurrence during follow-up. Statistical significance was accepted for p values of<0.05. RESULTS: A total of 593 patients were included - 412 patients with paroxysmal AF and 181 with persistent AF. After a mean follow-up of 24±6 months, overall single-procedure freedom from atrial arrhythmia was 76.4%. Individually, all biomarkers had no or only modest predictive power for recurrence. However, a TSH value >1.8 µUI/mL (HR=1.82 [95% CI, 1.89-2.80], p=0.006) was an independent predictor of arrhythmia recurrence. When assessing TSH, FT4 and BNP values in combination, each additional "abnormal" biomarker value was associated with a lower freedom from arrhythmia recurrence (87.1 % for no biomarker vs. 83.5% for one vs. 75.1% for two vs. 43.3% for three biomarkers, p<0.001). Patients with three "abnormal" biomarkers had a threefold higher risk of AF recurrence compared with no "abnormal" biomarker (HR=2.88 [95% CI, 1.39-5.17], p=0.003). CONCLUSIONS: When used in combination, abnormal TSH, FT4 and BNP values can be a useful tool for predicting arrhythmia recurrence after AI-guided AF ablation.


FUNDAMENTO: O software ablation index (AI) permitiu melhorar os resultados da ablação de fibrilação atrial (FA), mas as taxas de recorrência permanecem significativas. Biomarcadores séricos específicos têm sido associados a essa recorrência. OBJETIVOS: Avaliar se certos biomarcadores podem ser utilizados (individualmente ou combinados) para predizer a recorrência de FA pós ablação guiada pelo AI. MÉTODOS: Estudo multicêntrico, observacional, prospectivo de pacientes consecutivos, encaminhados para ablação de FA de janeiro de 2018 a março de 2021. Hemoglobina, peptídeo natriurético cerebral (BNP), proteína C reativa, troponina I ultrassensível, clearance de creatinina, Hormônio Tireoestimulante (TSH), e Tiroxina livre (T4) foram avaliados quanto à capacidade de prever a recorrência de arritmias durante o acompanhamento. Valores de p <0,05 foram aceitos como estatisticamente significativos. RESULTADOS: Um total de 593 pacientes foram incluídos ­ 412 com FA paroxística e 181 com FA persistente. Durante o seguimento médio de 24±6 meses, 76,4% não apresentaram recidiva após ablação. Individualmente, os biomarcadores demonstraram um valor preditivo baixo ou nulo para recorrência. No entanto, TSH >1,8 µUI/mL [HR=1,82 (IC95%, 1,89-2,80), p=0,006] foi um preditor independente de recorrência. Avaliando-se a combinação de TSH, FT4 e BNP, a adição de cada valor "anormal" foi associada a uma menor sobrevida livre de recorrência (87,1% se nenhum vs. 83,5% se um vs. 75,1% se dois vs. 43,3% se três biomarcadores, p<0,001). Doentes com três biomarcadores "anormais" apresentaram três vezes maior probabilidade de recorrência de FA, comparativamente aos que não apresentaram nenhum biomarcador "anormal" (HR=2,88 [IC95%, 1,39-5,17], p=0,003). CONCLUSÕES: Quando combinados, valores anormais de TSH, FT4 e BNP podem ser uma ferramenta útil para prever a recorrência de FA pós ablação guiada pelo AI.


Assuntos
Fibrilação Atrial , Biomarcadores , Ablação por Cateter , Recidiva , Tireotropina , Humanos , Fibrilação Atrial/cirurgia , Fibrilação Atrial/sangue , Biomarcadores/sangue , Masculino , Feminino , Estudos Prospectivos , Pessoa de Meia-Idade , Ablação por Cateter/métodos , Idoso , Tireotropina/sangue , Peptídeo Natriurético Encefálico/sangue , Valor Preditivo dos Testes , Proteína C-Reativa/análise , Resultado do Tratamento , Tiroxina/sangue , Fatores de Risco , Troponina I/sangue
2.
Rev Port Cardiol ; 2024 May 01.
Artigo em Inglês, Português | MEDLINE | ID: mdl-38701967

RESUMO

INTRODUCTION AND OBJECTIVES: Atrial fibrillation (AF) and heart failure (HF) often coexist. AF catheter ablation improves left ventricular ejection fraction (LVEF), but its impact varies between patients. We aimed to identify predictors of LVEF improvement in HF patients with impaired LVEF undergoing AF ablation. METHODS: We conducted a retrospective single-center study in HF patients with LVEF <50% undergoing AF catheter ablation between May 2016 and May 2022. The primary endpoint was the LVEF recovery rate ('responders'). Secondary endpoints were one-year safety and effectiveness. We also aimed to validate a prediction model for LVEF recovery. RESULTS: The study included 100 patients (79% male, median age 60 years, 70% with probable tachycardia-induced cardiomyopathy [TIC], mean LVEF 37%, 29% with paroxysmal AF). After a median follow-up of 12 months after catheter ablation, LVEF improved significantly (36±10% vs. 53±10%, p<0.001), with an 82% responder rate. A suspected diagnosis of TIC (OR 4.916 [95% CI 1.166-20.732], p=0.030), shorter QRS duration (OR 0.969 [95% CI 0.945-0.994], p=0.015), and smaller left ventricle (OR 0.893 [95% CI 0.799-0.999], p=0.049) were independently associated with LVEF improvement. Freedom from any documented atrial arrhythmia was 86% (64% under antiarrhythmic drugs), and the rate of adverse events was 2%. The prediction model had a good discriminative performance (AUC 0.814 [95% CI 0.681-0.947]). CONCLUSION: In AF patients with HF and impaired LVEF, suspected TIC, shorter QRS duration, and smaller LV diameter were associated with LVEF recovery following AF catheter ablation.

3.
J Appl Stat ; 51(5): 958-992, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38524799

RESUMO

Considering the context of functional data analysis, we developed and applied a new Bayesian approach via the Gibbs sampler to select basis functions for a finite representation of functional data. The proposed methodology uses Bernoulli latent variables to assign zero to some of the basis function coefficients with a positive probability. This procedure allows for an adaptive basis selection since it can determine the number of bases and which ones should be selected to represent functional data. Moreover, the proposed procedure measures the uncertainty of the selection process and can be applied to multiple curves simultaneously. The methodology developed can deal with observed curves that may differ due to experimental error and random individual differences between subjects, which one can observe in a real dataset application involving daily numbers of COVID-19 cases in Brazil. Simulation studies show the main properties of the proposed method, such as its accuracy in estimating the coefficients and the strength of the procedure to find the true set of basis functions. Despite having been developed in the context of functional data analysis, we also compared the proposed model via simulation with the well-established LASSO and Bayesian LASSO, which are methods developed for non-functional data.

4.
Int J Biol Macromol ; 265(Pt 2): 130933, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38508554

RESUMO

Glucans, a polysaccharide naturally present in the yeast cell wall that can be obtained from side streams generated during the fermentation process, have gained increasing attention for their potential as a skin ingredient. Therefore, this study focused on the extraction method to isolate and purify water-insoluble glucans from two different Saccharomyces cerevisiae strains: an engineered strain obtained from spent yeast in an industrial fermentation process and a wild strain produced through lab-scale fermentation. Two water-insoluble extracts with a high glucose content (> 90 %) were achieved and further subjected to a chemical modification using carboxymethylation to improve their water solubility. All the glucans' extracts, water-insoluble and carboxymethylated, were structurally and chemically characterized, showing almost no differences between both yeast-type strains. To ensure their safety for skin application, a broad safety assessment was undertaken, and no cytotoxic effect, immunomodulatory capacity (IL-6 and IL-8 regulation), genotoxicity, skin sensitization, and impact on the skin microbiota were observed. These findings highlight the potential of glucans derived from spent yeast as a sustainable and safe ingredient for cosmetic and skincare formulations, contributing to the sustainability and circular economy.


Assuntos
Glucanos , Saccharomyces cerevisiae , Glucanos/química , Saccharomyces cerevisiae/química , Polissacarídeos/química , Água
5.
Artif Intell Med ; 149: 102814, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38462277

RESUMO

Machine Learning models need large amounts of annotated data for training. In the field of medical imaging, labeled data is especially difficult to obtain because the annotations have to be performed by qualified physicians. Natural Language Processing (NLP) tools can be applied to radiology reports to extract labels for medical images automatically. Compared to manual labeling, this approach requires smaller annotation efforts and can therefore facilitate the creation of labeled medical image data sets. In this article, we summarize the literature on this topic spanning from 2013 to 2023, starting with a meta-analysis of the included articles, followed by a qualitative and quantitative systematization of the results. Overall, we found four types of studies on the extraction of labels from radiology reports: those describing systems based on symbolic NLP, statistical NLP, neural NLP, and those describing systems combining or comparing two or more of the latter. Despite the large variety of existing approaches, there is still room for further improvement. This work can contribute to the development of new techniques or the improvement of existing ones.


Assuntos
Processamento de Linguagem Natural , Radiologia , Aprendizado de Máquina
6.
Vaccines (Basel) ; 12(2)2024 Feb 13.
Artigo em Inglês | MEDLINE | ID: mdl-38400177

RESUMO

Carditis in childhood is a rare disease with several etiologies. We report a case of infant death due to pericarditis and myocarditis after the mRNA vaccine against COVID-19 (COVIDmRNAV). A 7-year-old male child received the first dose of the COVIDmRNAV and presented with monoarthritis and a fever non-responsive to oral antibiotics. The laboratory investigation showed signs of infection (leukocytosis, high levels of c-reactive protein). His condition rapidly deteriorated, and the patient died. The autopsy identified pericardial fibrin deposits, hemorrhagic areas in the myocardium, and normal valves. A diffuse intermyocardial inflammatory infiltrate composed of T CD8+ lymphocytes and histiocytes was identified. An antistreptolysin O (ASO) dosage showed high titers. The presence of arthritis, elevated ASO, and carditis fulfills the criteria for rheumatic fever. However, valve disease and Aschoff's nodules, present in 90% of rheumatic carditis cases, were absent in this case. The temporal correlation with mRNA vaccination prompted its inclusion as one of the etiologies. In cases of myocardial damage related to COVID-19mRNAV, it appears to be related to the expression of exosomes and lipid nanoparticles, leading to a cytokine storm. The potential effects of the COVID-19mRNAV must be considered in the pathogenesis of this disease, whether as an etiology or a contributing factor to a previously initiated myocardial injury.

7.
Port J Card Thorac Vasc Surg ; 30(4): 67-70, 2024 Feb 09.
Artigo em Inglês | MEDLINE | ID: mdl-38345884

RESUMO

Thoracic duct embolization has been increasingly adopted as a first-line therapy of chylothorax and this procedure includes lipiodol lymphangiography, thoracic duct access and embolization. Lymphangiography itself has a therapeutic role, with volume-dependent success rates of 37%-97% and even a reported 100% success rate in outputs of < 500 mL/day. We present a clinical case of a 48-years-old man diagnosed with esophageal squamous cell carcinoma, who underwent esophagectomy and presented with post-operative high-output (> 1L/day) chylothorax; thoracic duct embolization was proposed. Even though thoracic duct access and embolization were not achieved due to technical and anatomical factors, lipiodol lymphangiography and possibly thoracic duct maceration (after several punctures/attempts) contributed to the clinical success of the procedure, and this chylothorax with output values superior to those reported in the literature resolved within three days. As such, the therapeutic role of intranodal lymphangiography and thoracic duct disruption should be taken into account.


Assuntos
Quilotórax , Neoplasias Esofágicas , Carcinoma de Células Escamosas do Esôfago , Humanos , Masculino , Pessoa de Meia-Idade , Quilotórax/diagnóstico por imagem , Neoplasias Esofágicas/cirurgia , Óleo Etiodado , Linfografia/métodos , Ducto Torácico/diagnóstico por imagem
8.
Healthcare (Basel) ; 12(2)2024 Jan 12.
Artigo em Inglês | MEDLINE | ID: mdl-38255075

RESUMO

The biopsychosocial development of individuals is influenced by body image and physical exercise. This study aimed to evaluate seven hypotheses regarding the impact of positive affect, negative affect, self-consciousness of appearance, and positive body image on the practice of physical exercise. The data were processed using the statistical package SmartPLS 4.0.9.5. Using an exploratory methodology based on structural equation modeling (SEM) of structural equations applied to small sample sizes, a tentative model has been generated to define the drivers of physical activity. The survey used the Body Mass Index, Body Appreciation Scale-Revised, and Derriford Appearance Scale-14 items. The study involved 129 men and 279 women (N = 408). The model demonstrated a distinct internal consistency in that, out of the seven hypotheses analyzed, only one was rejected. The findings of the multigroup analysis indicate that there are no statistically significant discrepancies between the constructed measures and the practice of physical activity. The conclusions of this study showed that, although positive and negative affect, and self-consciousness influence positive body image, there were no statistically significant differences between those who exercise and those who do not exercise. Various factors influence biopsychosocial development. Future studies should explore the influence of psychological and social variables on understanding body image and physical exercise.

9.
Cardiol Young ; 34(4): 782-787, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-37828640

RESUMO

INTRODUCTION: Cardiac arrhythmias are a major concern in patients with CHD. The purpose of this study was to evaluate the long-term outcomes in patients with CHD submitted to catheter ablation. MATERIALS AND METHODS: Observational retrospective study of patients with CHD referred for catheter ablation from January 2016 to December 2021 in a tertiary referral centre. Acute procedural endpoints and long-term outcomes were assessed. RESULTS: A total of 44 ablation procedures were performed in 36 CHD patients (55% male, mean age 43 ±3 years). Fifty-four arrhythmias were ablated: 23 cavotricuspid isthmus atrial flutters, 10 atrial re-entrant tachycardias, eight focal atrial tachycardias, eight atrial fibrillations, three atrioventricular re-entrant tachycardias, and two ventricular tachycardias. During a median follow-up time of 37 months (interquartile range 12-51), freedom from arrhythmia recurrence was achieved in 93%, with 1.2 procedures per patient (18% with anti-arrhythmic drugs). There were no adverse events related to catheter ablation. No predictors of recurrence were identified. CONCLUSION: In patients with CHD, catheter ablation presents a high mid-term efficacy while maintaining a safe profile.


Assuntos
Fibrilação Atrial , Ablação por Cateter , Cardiopatias Congênitas , Taquicardia Supraventricular , Taquicardia Ventricular , Humanos , Masculino , Adulto , Pessoa de Meia-Idade , Feminino , Estudos Retrospectivos , Cardiopatias Congênitas/cirurgia , Fibrilação Atrial/etiologia , Taquicardia Supraventricular/cirurgia , Ablação por Cateter/métodos , Taquicardia Ventricular/etiologia , Resultado do Tratamento
10.
BMC Cardiovasc Disord ; 23(1): 609, 2023 12 12.
Artigo em Inglês | MEDLINE | ID: mdl-38087189

RESUMO

BACKGROUND: There is a lack of evidence regarding contemporary implantable cardioverter-defibrillator (ICD) battery longevity. Our aim was to assess battery longevity in ICDs in a real-world setting. METHODS: Retrospective cross-sectional single center study of a prospectively collected database of consecutive patients who underwent ICD implantation from January 2010 to December 2015. Clinical data and battery longevity of all manufacturers were collected. RESULTS: A total of 351 patients (84.6% males, mean age of 61 ± 12 years) were included in the study (292 VVI; 6 VDD; 53 DDD). All manufacturers (Abbott, Biotronik, Boston, Medtronic and Microport) were equally represented in the study (p = 0.110). Median battery longevity was 10.8 years (11 years for VVI and 8.5 for DDD). After a follow-up time of 5 years, 98% of VVI and DDD were still in service (vs. industry-projected longevity of 98%). During this time, 89 patients (25.4%) underwent device replacement - 69 patients (77.5%) due to battery depletion, 6 patients due to infection, 3 patients due to dysfunction and 13 patients due to upgrade to CRT-D. Patients with Medtronic or Biotronik ICDs had a greater probability of being replaced earlier due to battery depletion (Biotronik HR 6.87, 95% CI 2.54-18.58, p < 0.001; Medtronic HR 6.08, 95% CI 2.45-15.06 p < 0.001). CONCLUSIONS: VVI and DDD ICD battery longevity matched industry-projected longevity after 5 years of follow-up. Medtronic and Biotronik ICDs appeared to have an earlier battery depletion. Further randomized studies are required to ensure optimal care.


Assuntos
Desfibriladores Implantáveis , Insuficiência Cardíaca , Masculino , Humanos , Pessoa de Meia-Idade , Idoso , Feminino , Falha de Equipamento , Estudos Retrospectivos , Estudos Prospectivos , Estudos Transversais , Desenho de Equipamento , Estimativa de Kaplan-Meier , Fatores de Tempo , Remoção de Dispositivo
11.
JBI Evid Implement ; 21(S1): S19-S27, 2023 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-38037445

RESUMO

OBJECTIVES: To improve postdischarge telephone follow-up in the context of chronic disease management (peripheral artery disease), in a vascular surgery service. INTRODUCTION: Patients with chronic diseases, such as peripheral artery disease, present a higher risk of complications and greater constraints regarding their adherence to treatment, leading to an increasing mortality rate and decreased functional capacity. Comprehensive discharge planning plus postdischarge telephone follow-up may reduce 30-day re-hospitalization rates. METHODS: The project used the JBI audit and feedback methodological approach to implement the best available evidence into practice. Two audit criteria were used: existence of comprehensive discharge planning and timely telephone follow-up. A baseline audit was conducted, followed by analysis of barriers, which led to the implementation of several strategies, namely, a targeted training program, the development of educational resources and standardized procedures for the discharge process, and postdischarge telephone follow-up. RESULTS: Results from the baseline and first follow-up audits showed improvement for both criteria. Compliance for criterion 1 (comprehensive discharge planning, including postdischarge telephone follow-up) increased from 0% to 40.7%, and for criterion 2 (patient is followed up by telephone within 2 weeks of discharge) increased from 0% to 44.4%. These two criteria sustained improvements in the second follow-up audit: compliance increased to 45% (criterion 1) and 60% (criterion 2). CONCLUSIONS: This implementation project contributed to the optimization of the chronic disease management, including improved compliance with discharge planning and early postdischarge telephone follow-up.


Assuntos
Alta do Paciente , Doença Arterial Periférica , Humanos , Assistência ao Convalescente , Seguimentos , Doença Crônica , Telefone , Procedimentos Cirúrgicos Vasculares
12.
Biodivers Data J ; 11: e110415, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38098784

RESUMO

Background: With the increasing recognition of the significance of arachnid conservation, it is crucial to allocate greater efforts towards implementing targeted monitoring programmes. Despite recent studies, our understanding of arachnid populations in Portugal remains limited. This study serves as the initial inventory of arachnids (Araneae and Opiliones) within the Castro Verde Special Protection Area (SPA) located in Beja, southern Portugal. The surveys were conducted during the spring of 2012 across 80 open grasslands that were grazed by cattle and sheep. New information: A total of 71 species of Araneae and two species of Opiliones have been identified. Notably, three spider species, namely Argennasubnigra, Civizelotesibericus and Walckenaeriacucullata, are documented for the first time in Portugal. Additionally, two harvestmen species (Dasylobusibericus and Homalenotusbuchneri) and 14 spider species (Cheiracanthiumpennatum, Haplodrassusrhodanicus, Marinarozelotesminutus, Tapinocybaalgirica, Agraecinalineata, Tibellusmacellus, Talaverapetrensis, Tetragnathaintermedia, Dipoenaumbratilis, Enoplognathadiversa, Neottiurauncinata, Ruborridionmusivum, Theridionpinastri and Xysticusgrallator) are recorded for the first time in the Beja District. The occurrence of each documented species within the SPA, including family and species details, is presented, underscoring the significance of the Castro Verde SPA for arachnid conservation. These findings contribute novel insights into the biodiversity of the Castro Verde SPA, emphasising the necessity of incorporating this area into arachnid diversity conservation efforts.

13.
Cureus ; 15(10): e47680, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-38022115

RESUMO

Placenta accreta spectrum disorder is a pregnancy-related disorder responsible for important post-partum morbimortality, associated with intractable or massive hemorrhage, leading to uterine loss in up to 64% of women. Despite international recommendations advocating planned preterm cesarean hysterectomy for the management of these patients, uterus preservation management is being continuously reported with the implementation of minimally invasive bleeding reduction strategies, such as prophylactic balloon-assisted occlusion. We present the case of a 40-year-old pregnant woman with a previous cesarean, diagnosed with placenta previa and suspected placenta accreta on magnetic resonance after having second-trimester vaginal bleeding. A peri-operative multidisciplinary panel was involved, in collaboration with the interventional radiologist, and the c-section was scheduled for 36 weeks of gestation. The prophylactic balloon-assisted occlusion was successfully performed, minimizing the blood loss and allowing a uterus-preserving approach.

14.
Eur J Investig Health Psychol Educ ; 13(11): 2546-2560, 2023 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-37998067

RESUMO

The COVID-19 pandemic has caused substantial disruptions in the lives of higher education students, with detrimental repercussions for academic performance and overall mental health. Therefore, we aimed to evaluate the prevalence of depression, anxiety, and stress symptoms among Portuguese higher education students during the first wave of the coronavirus pandemic and investigate DASS-21's psychometric characteristics and whether it functions effectively during a pandemic. A convenience sampling procedure was used to recruit 1522 participants (75.1% women and 79.2% undergraduate students) for this cross-sectional research. Participants completed an e-survey created using DASS-21. The results revealed a considerable prevalence of symptoms of depression [≥10] (N = 434, 28.5%), anxiety [≥7] (N = 551, 36.2%), and stress [≥11] (N = 544, 35.7%). Confirmatory factor analysis (CFA) revealed the scale's three-factor structure, which matched the three DASS-21 subscales. Subsequently, the heterotrait-monotrait (HTMT) correlation ratio evaluated the scale's discriminant validity, which was relatively good. Cronbach's alpha measured the internal consistency of the DASS subscales, which was excellent (Cronbach's α > 0.90). DASS-21 was shown to be a reliable and appropriate measure for assessing students' mental health. Furthermore, DASS-21 is recommended for use by academics and healthcare professionals in measuring students' psychological distress. Further validation studies of this scale are needed with larger and more representative samples.

15.
Carbohydr Polym ; 322: 121329, 2023 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-37839841

RESUMO

ß-Glucans, which are naturally present in cereals, yeast, and mushrooms, have gained attention as a potential natural source for functional foods and pharmaceuticals. Due to the availability of ß-glucans from several sources, different extraction methods can be employed to obtain high purity extracts that can be further modified to enhance their solubility or other biological properties. Apart from their known ability to interact with the immune system, ß-glucans possess specific properties that could benefit overall skin health and prevent age-related signs, including soothing and antioxidant activities. As a result, the use of ß-glucans to mitigate damage caused by environmental stressors or skin-related issues that accelerate skin aging or trigger chronic inflammation may represent a promising, natural, eco-friendly, and cost-effective approach to maintaining skin homeostasis balance. This review outlines ß-glucan extraction methodologies, molecular structure, functionalization approaches, and explores skin-related benefits of ß-glucans, along with an overview of related products in the market.


Assuntos
Agaricales , beta-Glucanas , beta-Glucanas/uso terapêutico , beta-Glucanas/química , Agaricales/química , Pele , Antioxidantes/farmacologia , Antioxidantes/uso terapêutico , Solubilidade
16.
Biosensors (Basel) ; 13(10)2023 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-37887106

RESUMO

Modern drug discovery relies on combinatorial screening campaigns to find drug molecules targeting specific disease-associated proteins. The success of such campaigns often relies on functional and structural information of the selected therapeutic target, only achievable once its purification is mastered. With the aim of bypassing the protein purification process to gain insights on the druggability, ligand binding, and/or characterization of protein-protein interactions, herein, we describe the Extract2Chip method. This approach builds on the immobilization of site-specific biotinylated proteins of interest, directly from cellular extracts, on avidin-coated sensor chips to allow for the characterization of molecular interactions via surface plasmon resonance (SPR). The developed method was initially validated using Cyclophilin D (CypD) and subsequently applied to other drug discovery projects in which the targets of interest were difficult to express, purify, and crystallize. Extract2Chip was successfully applied to the characterization of Yes-associated protein (YAP): Transcriptional enhancer factor TEF (TEAD1) protein-protein interaction inhibitors, in the validation of a ternary complex assembly composed of Dyskerin pseudouridine synthase 1 (DKC1) and RuvBL1/RuvBL2, and in the establishment of a fast-screening platform to select the most suitable NUAK family SNF1-like kinase 2 (NUAK2) surrogate for binding and structural studies. The described method paves the way for a potential revival of the many drug discovery campaigns that have failed to deliver due to the lack of suitable and sufficient protein supply.


Assuntos
Descoberta de Drogas , Ressonância de Plasmônio de Superfície , Ressonância de Plasmônio de Superfície/métodos , Descoberta de Drogas/métodos , Proteínas , Cromatografia de Afinidade , Ligação Proteica
17.
Int Angiol ; 42(5): 371-381, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37870494

RESUMO

BACKGROUND: In peripheral arterial disease (PAD) patients with intermittent claudication (IC), the combination of aerobic and resistance exercises could counteract muscle loss and attenuate disease progression. This study analyzed the effects of six months of a combined exercise program on walking ability, lower limb body composition, cardiovascular risk factors, and Ankle-Brachial Index (ABI). METHODS: Twenty-three patients (age 63.2±1.5 years and ABI 0.58±0.07) with PAD and IC were allocated to a control group (CG) or a supervised exercise group (SUP). Ten patients underwent six months of treadmill walking combined with resistance exercises, three times a week. The CG (N.=13) received a recommendation for walking. All patients were measured at baseline (M0), after three months (M3), and six months (M6). RESULTS: During constant treadmill protocol, the claudication onset time/distance (COT/COD), absolute claudication time/distance (ACT/ACD), and number of pauses of overall patients significantly improved at M3 and M6. Between groups were found significant differences in COT and COD at M6 (P=0.005 and P=0.007, respectively); and in ACT and ACD at M3 (P=0.003 for both) and at M6 (P=0.005 and P=0.005, respectively), with major improvements in the SUP. Over the six months, a significant group effect was found in fat-free mass (P=0.041) and predicted muscle mass (P=0.039) of the lower ABI leg, with greater improvements in the SUP. CONCLUSIONS: A supervised exercise program that combines aerobic and resistance training improves PAD symptoms and has additional benefits for patients. Patients in the program showed improvements in walking ability, lower-limb body composition, perceived exertion, and heart rate during treadmill walking.


Assuntos
Doença Arterial Periférica , Humanos , Pessoa de Meia-Idade , Projetos Piloto , Doença Arterial Periférica/diagnóstico , Doença Arterial Periférica/terapia , Claudicação Intermitente/diagnóstico , Claudicação Intermitente/terapia , Claudicação Intermitente/etiologia , Exercício Físico , Caminhada/fisiologia , Terapia por Exercício/métodos , Teste de Esforço/efeitos adversos
18.
Chem Res Toxicol ; 36(9): 1471-1482, 2023 09 18.
Artigo em Inglês | MEDLINE | ID: mdl-37566384

RESUMO

Adductomics studies are used for the detection and characterization of various chemical modifications (adducts) of nucleic acids and proteins. The advancements in liquid chromatography coupled with high-resolution tandem mass spectrometry (HRMS/MS) have resulted in efficient methods for qualitative and quantitative adductomics. We developed an HRMS-based method for the simultaneous analysis of RNA and DNA adducts in a single run and demonstrated its application using Baltic amphipods, useful sentinels of environmental disturbances, as test organisms. The novelty of this method is screening for RNA and DNA adducts by a single injection on an Orbitrap HRMS instrument using full scan and data-independent acquisition. The MS raw files were processed with an open-source program, nLossFinder, to identify and distinguish RNA and DNA adducts based on the characteristic neutral loss of ribonucleosides and 2'-deoxyribonucleosides, respectively. In the amphipods, in addition to the nearly 150 putative DNA adducts characterized earlier, we detected 60 putative RNA adducts. For the structural identification of the detected RNA adducts, the MODOMICS database was used. The identified RNA adducts included simple mono- and dimethylation and other larger functional groups on different ribonucleosides and deaminated product inosine. However, 54 of these RNA adducts are not yet structurally identified, and further work on their characterization may uncover new layers of information related to the transcriptome and help understand their biological significance. Considering the susceptibility of nucleic acids to environmental factors, including pollutants, the developed multi-adductomics methodology with further advancement has the potential to provide biomarkers for diagnostics of pollution effects in biota.


Assuntos
Adutos de DNA , RNA , DNA , Espectrometria de Massas em Tandem/métodos , Cromatografia Líquida
19.
Front Vet Sci ; 10: 1137888, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37601753

RESUMO

This report describes consensus guidelines and recommendations for the treatment of canine osteoarthritis (OA) according to the "Canine OsteoArthritis Staging Tool excluding radiography" (COASTeR) stage of OA, by the COAST Development Group. The recommendations are based on evidence-based medicine and clinical experience and are proposed with international relevance in mind. The aim is to provide veterinarians with a practical reference to consolidated information and to support the development of patient-specific OA management protocols and informed treatment choices based on the stage of OA.

20.
World J Clin Cases ; 11(20): 4883-4889, 2023 Jul 16.
Artigo em Inglês | MEDLINE | ID: mdl-37584006

RESUMO

BACKGROUND: The gold standard treatment for papillary thyroid carcinoma is total thyroidectomy and indications for microwave thermal ablation for primary thyroid cancers have not yet been clearly established However, some patients refuse surgery and others have no indication for it, for example patients under palliative care as in this case, or cannot undergo surgery, based on their comorbidities. These indications are described in the most recent Korean, North American and European guidelines. Laser ablation, radiofrequency ablation, and microwave ablation are similarly safe and effective, so the choice should be based on the specific competences and resources of the pertaining centers. These indications are Percutaneous minimally-invasive techniques; they can be useful to stop disease progression and as an alternative to surgery in patients with contraindication or who refuse surgery. We present a case of a thyroid papillary carcinoma with 17 mm effectively treated with microwave thermal ablation and without recurrence after one year of follow up. CASE SUMMARY: The authors present a case of a 71-years-old patient with a left lobe papillary thyroid carcinoma with 13 mm × 17 mm × 13 mm, with no indication for thyroid surgery given the context of another cancer in palliative treatment. Microwave thermoablation was performed on December 2021. Four months later he repeated computed tomography (CT) scan, which showed that the tumor had disappeared. Six months after ablation he underwent a positron emission tomography/CT-fluorodeoxyglucose scan, which didn't show any evidence of hypermetabolic tumor lesions. CONCLUSION: This case shows microwave thermoablation can be a safe and effective alternative to surgery in patients with no conditions to undergo surgery or when they refuse it. By treating the tumor, with this minimally invasive technique, we are stopping its growth and avoiding disease progression.

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