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1.
Comput Biol Med ; 174: 108454, 2024 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-38608326

RESUMO

BACKGROUND: Effective and timely detection is vital for mitigating the severe impacts of Sexually Transmitted Infections (STI), including syphilis and HIV. Cyclic Voltammetry (CV) sensors have shown promise as diagnostic tools for these STI, offering a pathway towards cost-effective solutions in primary health care settings. OBJECTIVE: This study aims to pioneer the use of Fourier Descriptors (FDs) in analyzing CV curves as 2D closed contours, targeting the simultaneous detection of syphilis and HIV. METHODS: Raw CV signals are filtered, resampled, and transformed into 2D closed contours for FD extraction. Essential shape characteristics are captured through selected coefficients. A complementary geometrical analysis further extracts features like curve areas and principal axes lengths from CV curves. A Mahalanobis Distance Classifier is employed for differentiation between patient and control groups. RESULTS: The evaluation of the proposed method revealed promising results with classification performance metrics such as Accuracy and F1-Score consistently achieving values rounded to 0.95 for syphilis and 0.90 for HIV. These results underscore the potential efficacy of the proposed approach in differentiating between patient and control samples for STI detection. CONCLUSION: By integrating principles from biosensors, signal processing, image processing, machine learning, and medical diagnostics, this study presents a comprehensive approach to enhance the detection of both syphilis and HIV. This setts the stage for advanced and accessible STI diagnostic solutions.

2.
BMC Infect Dis ; 24(1): 100, 2024 Jan 18.
Artigo em Inglês | MEDLINE | ID: mdl-38238649

RESUMO

BACKGROUND: Despite their higher risk of developing severe disease, little is known about the burden of influenza in Portugal in children aged < 5 years old. This study aims to cover this gap by estimating the clinical and economic burden of severe influenza in children, in Portugal, during ten consecutive influenza seasons (2008/09-2017/18). METHODS: We reviewed hospitalizations in children aged < 5 years old using anonymized administrative data covering all public hospitals discharges in mainland Portugal. The burden of hospitalization and in-hospital mortality directly coded as due to influenza was supplemented by the indirect burden calculated from excess hospitalization and mortality (influenza-associated), estimated for four groups of diagnoses (pneumonia or influenza, respiratory, respiratory or cardiovascular, and all-cause), through cyclic regression models integrating the incidence of influenza. Means were reported excluding the H1N1pdm09 pandemic (2009/10). RESULTS: The mean annual number of hospitalizations coded as due to influenza was 189 (41.3 cases per 100,000 children aged < 5 years old). Hospitalization rates decreased with increasing age. Nine-in-ten children were previously healthy, but the presence of comorbidities increased with age. Children stayed, on average, 6.1 days at the hospital. Invasive mechanical ventilation was used in 2.4% of hospitalizations and non-invasive in 3.1%. Influenza-associated excess hospitalizations between 2008 and 2018 were estimated at 1,850 in pneumonia or influenza, 1,760 in respiratory, 1,787 in respiratory or cardiovascular, and 1,879 in all-cause models. A total of 95 influenza-associated excess deaths were estimated in all-cause, 14 in respiratory or cardiovascular, and 9 in respiratory models. Over ten years, influenza hospitalizations were estimated to have cost the National Health Service at least €2.9 million, of which 66.5% from healthy children. CONCLUSIONS: Influenza viruses led to a high number of hospitalizations in children. Most were previously healthy. Results should lead to a reflection on the adequate preventive measures to protect this age group.


Assuntos
Influenza Humana , Pneumonia , Pré-Escolar , Humanos , Lactente , Hospitalização , Pneumonia/epidemiologia , Portugal/epidemiologia , Estações do Ano , Medicina Estatal
3.
Biotechnol J ; 19(1): e2300219, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37876300

RESUMO

Chitinases are widely studied enzymes that have already found widespread application. Their continued development and valorisation will be driven by the identification of new and improved variants and/or novel applications bringing benefits to industry and society. We previously identified a novel application for chitinases wherein the Candida albicans cell wall surface chitinase 3 (Cht3) was shown to have potential in vaccine applications as a subunit antigen against fungal infections. In the present study, this enzyme was investigated further, developing production and purification protocols, enriching our understanding of its properties, and advancing its application potential. Cht3 was heterologously expressed in Pichia pastoris and a 4-step purification protocol developed and optimised: this involves activated carbon treatment, hydrophobic interaction chromatography, ammonium sulphate precipitation, and gel filtration chromatography. The recombinant enzyme was shown to be mainly O-glycosylated and to retain the epitopes of the native protein. Functional studies showed it to be highly specific, displaying activity on chitin, chitosan, and chito-oligosaccharides larger than chitotriose only. Furthermore, it was shown to be a stable enzyme, exhibiting activity, and stability over broad pH and temperature ranges. This study represents an important step forward in our understanding of Cht3 and contributes to its development for application.


Assuntos
Quitinases , Quitosana , Candida albicans/genética , Candida albicans/metabolismo , Quitinases/genética , Quitinases/química , Proteínas , Quitina/química , Quitina/metabolismo , Concentração de Íons de Hidrogênio
4.
Cureus ; 15(11): e49494, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-38152805

RESUMO

Drug-induced long QT syndrome (LQTS) is defined as prolonged corrected QT interval (QTc ≥460 ms) plus polymorphic ventricular arrhythmia fitting the description of torsades de pointes temporally associated with the administration of a drug or combination of drugs. Amiodarone therapy is a known uncommon cause of acquired QT interval prolongation that should not be underestimated. We present a case of an iatrogenic electrical storm with atrial fibrillation (AF) in which amiodarone was administered to attempt chemical cardioversion, resulting in an unnoticed prolongation of the QT interval, with subsequent repeated polymorphic ventricular tachycardia, managed with isoproterenol. Concomitant drugs and slight electrolyte disturbances potentiated this phenomenon. Given the widespread use of this drug in the emergency department, our case highlights a pertinent matter for all medical emergency practitioners. Additionally, it stresses the significance of potential precipitating factors, such as electrolyte imbalances, which are clinical conditions very frequent in the emergency context, along with the importance of recognizing drug interactions. Finally, this case also emphasizes the vital importance of closely monitoring the patient's receiving amiodarone.

5.
Front Immunol ; 14: 1267621, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38022643

RESUMO

Introduction: The clinical prognosis of the HER2-overexpressing (HER2-OE) subtype of breast cancer (BC) is influenced by the immune infiltrate of the tumor. Specifically, monocytic cells, which are promoters of pro-tumoral immunosuppression, and NK cells, whose basal cytotoxic function may be enhanced with therapeutic antibodies. One of the standards of care for HER2+ BC patients includes the combination of the anti-HER2 antibodies trastuzumab and pertuzumab. This dual combination was a breakthrough against trastuzumab resistance; however, this regimen does not yield complete clinical benefit for a large fraction of patients. Further therapy refinement is still hampered by the lack of knowledge on the immune mechanism of action of this antibody-based dual HER2 blockade. Methods: To explore how the dual antibody challenge influences the phenotype and function of immune cells infiltrating the HER2-OE BC microenvironment, we developed in vitro 3D heterotypic cell models of this subtype. The models comprised aggregates of HER2+ BC cell lines and human peripheral blood mononuclear cells. Cells were co-encapsulated in a chemically inert alginate hydrogel and maintained in agitation-based culture system for up to 7 days. Results: The 3D models of the HER2-OE immune microenvironment retained original BC molecular features; the preservation of the NK cell compartment was achieved upon optimization of culture time and cytokine supplementation. Challenging the models with the standard-of-care combination of trastuzumab and pertuzumab resulted in enhanced immune cytotoxicity compared with trastuzumab alone. Features of the response to therapy within the immune tumor microenvironment were recapitulated, including induction of an immune effector state with NK cell activation, enhanced cell apoptosis and decline of immunosuppressive PD-L1+ immune cells. Conclusions: This work presents a unique human 3D model for the study of immune effects of anti-HER2 biologicals, which can be used to test novel therapy regimens and improve anti-tumor immune function.


Assuntos
Antineoplásicos , Neoplasias da Mama , Humanos , Feminino , Neoplasias da Mama/patologia , Leucócitos Mononucleares/metabolismo , Linhagem Celular Tumoral , Trastuzumab/farmacologia , Trastuzumab/uso terapêutico , Antineoplásicos/uso terapêutico , Microambiente Tumoral
6.
GE Port J Gastroenterol ; 30(5): 368-374, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37868631

RESUMO

Background: Colorectal cancer (CRC) is a leading cause of cancer. The detection of pre-malignant lesions by colonoscopy is associated with reduced CRC incidence and mortality. Narrow band imaging has shown promising but conflicting results for the detection of serrated lesions. Methods: We performed a randomized clinical trial to compare the mean detection of serrated lesions and hyperplastic polyps ≥10 mm with NBI or high-definition white light (HD-WL) withdrawal. We also compared all sessile serrated lesions (SSLs), adenoma, and polyp prevalence and rates. Results: Overall, 782 patients were randomized (WL group 392 patients; NBI group 390 patients). The average number of serrated lesions and hyperplastic polyps ≥10 mm detected per colonoscopy (primary endpoint) was similar between the HD-WL and NBI group (0.118 vs. 0.156, p = 0.44). Likewise, the adenoma detection rate (55.2% vs. 53.2%, p = 0.58) and SSL detection rate (6.8% vs. 7.5%, p = 0.502) were not different between the two study groups. Withdrawal time was higher in the NBI group (10.88 vs. 9.47 min, p = 0.004), with a statistically nonsignificant higher total procedure time (20.97 vs. 19.30 min, p = 0.052). Conclusions: The routine utilization of narrow band imaging does not improve the detection of serrated class lesions or any pre-malignant lesion and increases the withdrawal time.


Introdução: O cancro do cólon e reto é a neoplasia mais frequente considerando os dois géneros. . A deteção de lesões pré-malignas por colonoscopia está associada a uma redução da incidência e da mortalidade. Estudos sobre a utilização da luz de banda estreita (NBI) na deteção de lesões serreadas tiveram resultados promissores, mas heterogéneos. Métodos: Realizámos um ensaio clínico randomizado para comparar o número médio de lesões serreadas e lesões hiperplásicas ≥10 mm com NBI ou luz branca de alta-definição (HD-WL). Como resultados secundários comparámos a prevalência e as taxas de deteção de lesões serreadas sésseis, adenomas e todas as lesões. Resultados: Foram randomizados 782 doentes (392 no grupo HD-WL e 390 no grupo NBI). O número médio de lesões serreadas e hiperplásicas ≥10 mm não apresentou diferença estatisticamente significativa entre dois grupos (0.118 vs. 0.156, p = 0.44). A taxa de deteção de adenomas (55.2% vs. 53.2%, p = 0.58) e a taxa de deteção de lesões serreadas sésseis (6.8% vs. 7.5%, p = 0.502) também não foram diferentes. O tempo de retirada foi maior no grupo NBI (10.88 vs. 9.47 min, p = 0.004) e o tempo total de procedimento teve um ligeiro aumento não atingindo significância estatística (20.97 vs. 19.30 min, p = 0.052). Conclusão: A utilização da luz NBI por rotina não aumenta a deteção de lesões serreadas nem de qualquer lesão pré-maligna e aumenta o tempo de retirada na colonoscopia.

7.
GE Port J Gastroenterol ; 30(5): 336-342, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37868636

RESUMO

Introduction: This study aimed to evaluate the effect of small-bowel angioectasia on survival, given the hypothesis that angioectasia might be an independent risk factor of frailty and poor outcomes. Methods: In this retrospective cohort study, all patients undergoing small-bowel capsule endoscopy between 2010 and 2013 for obscure gastrointestinal bleeding from a Portuguese tertiary centre were included. Follow-up started after capsule endoscopy and ended upon death or end of the study (November 2020). Survival analysis was performed using a Cox proportional-hazards model, in order to analyse the effect of small-bowel angioectasia on survival as well as potentially confounding factors (age, vascular diseases and chronic kidney disease). Results: A total of 176 patients were included in this study (50.6% male), with a median age of 68.5 years (IQR 24). The median follow-up was 7 years (IQR 4), during which 67 (38.1%) patients died. Seventy-three (41.5%) patients had at least one small-bowel angioectasia on capsule endoscopy. On multivariate Cox regression analysis, only age, peripheral arterial disease, history of previous mesenteric ischaemia and chronic kidney disease were independent risk factors of death. The presence of small-bowel angioectasia did not affect survival in this analysis (HR 1.30; 95% CI 0.75-2.23; p = 0.35). Conclusion: In this retrospective cohort study, some comorbidities and age were independent predictors of poor survival. The presence of small-bowel angioectasia per se did not affect survival.


Introdução: Este estudo pretendeu avaliar a influência das angiectasias do intestino delgado na sobrevida, dada a hipótese de que as angiectasias pudessem constituir um fator de risco independente para fragilidade e outcomes adversos. Métodos: Os autores incluíram neste estudo de coorte retrospetivo todos os doentes submetidos a cápsula endoscópica entre 2010 e 2013 por hemorragia digestiva obscura num centro português terciário. O followup iniciou-se após a realização da cápsula e terminou aquando da morte ou fim do estudo (Novembro de 2020). A análise da sobrevida foi realizada através de um modelo de regressão de Cox, no sentido de analisar o efeito na sobrevida das angiectasias do intestino delgado e de potenciais fatores confundidores (idade, doenças vasculares e doença renal crónica). Resultados: Neste estudo foram incluídos 176 doentes (50.6% do sexo masculino), com uma idade mediana de 68.5 anos (IQR 24). O tempo de follow-up mediano foi de 7 anos (IQR 4), durante o qual se verificaram 67 (38.1%) óbitos. 73 (41.5%) dos doentes apresentavam pelo menos uma angiectasia no intestino delgado. Na análise de sobrevida, apenas a idade, doença arterial periférica, história prévia de isquemia mesentérica e doença renal crónica foram fatores de risco independentes de mortalidade. A presença de angiectasias no intestino delgado não afetou a sobrevida nesta amostra (HR 1,30; 95% CI 0,75­2,23; p = 0.35). Conclusão: Neste estudo de coorte retrospetivo, algumas co-morbilidades e a idade foram fatores de risco independentes de mortalidade. A presença de angiectasias no intestino delgado, per se, não afetou a sobrevida.

8.
Turk J Gastroenterol ; 34(11): 1150-1155, 2023 11.
Artigo em Inglês | MEDLINE | ID: mdl-37768309

RESUMO

BACKGROUND/AIMS: In the past, dye-spraying chromoendoscopy was the technique of choice for colonic surveillance in patients with long-standing extensive inflammatory bowel disease. Recent evidence suggests that virtual chromoendoscopy is an equally acceptable technique. MATERIALS AND METHODS: Eleven gastroenterologists were given a survey with 20 pairs of pictures from inflammatory bowel disease surveillance colonoscopies (10 with nondysplastic lesions, 5 with dysplastic lesions, and 5 with no lesions). Each pair contained the same image captured during colonoscopy using indigo carmine and narrow-band imaging. For each picture, the gastroenterologist assessed the presence/absence of lesion and, when a lesion was identified, assessed the presence/absence of dysplasia and delineated its margins. To compare lesion and dysplasia detection between techniques, sensitivity, specificity, and interobserver agreement were calculated. The chi-square test was used to assess the accuracy of margins delineation. RESULTS: When assessing lesion and dysplasia detection, similar sensitivity and specificity values were obtained for both techniques. Interobserver agreement analysis revealed that dye-spraying chromoendoscopy and virtual chromoendoscopy had a moderate agreement in lesion detection but, for dysplasia detection, dye-spraying chromoendoscopy had a slight agreement [K = 0.11 (0.03-0.18), P < .01] and virtual chromoendoscopy a fair agreement [K = 0.30 (0.22-0.37), P < .01]. Margin delineation was similar between techniques. CONCLUSION: Sensitivity and specificity for lesion and dysplasia detection, as well as the accuracy of margins delineation, were similar between dye-spraying chromoendoscopy and virtual chromoendoscopy. Interobserver agreement for dysplasia detection was suboptimal in both techniques; however, it was superior when using virtual chromoendoscopy. These findings suggest that virtual chromoendoscopy constitutes a valid alternative for dysplasia screening in inflammatory bowel disease.


Assuntos
Doenças do Colo , Doenças Inflamatórias Intestinais , Humanos , Corantes , Doenças Inflamatórias Intestinais/diagnóstico por imagem , Doenças Inflamatórias Intestinais/patologia , Colonoscopia/métodos , Hiperplasia
9.
GE Port J Gastroenterol ; 30(3): 230-238, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-37387712

RESUMO

Introduction: The European Society of Gastrointestinal Endoscopy (ESGE) identified the need to benchmark the quality of small bowel capsule endoscopy (SBCE) and produced a set of performance measures (PM). The aim of this study is to critically evaluate the accordance of the PM for SBCE in two Portuguese centers with different SBCE platforms. Methods: The authors conducted a cross-sectional analysis of consecutive SBCE performed in an 18-month period in 2 Portuguese centers that used two different SBCE platforms Mirocam® (IntroMedic, Seoul, South Korea) and PillCam® (Medtronic, Yokneam, Israel). A total of 10 PM (6 key, 4 minor) were evaluated and compared between the 2 centers. Results: A total of 493 SBCE were included. The minimum standard established by ESGE was reached in 3/6 key PM (complete visualization, lesion detection rate, and capsule retention rate), and none of the 4 minor PM. PM compliance significantly differed between the 2 centers: complete small bowel visualization 95.9 and 90% (p = 0.01), diagnostic yield 50.6 and 63% (p = 0.005), adequate small bowel cleansing level according to Brotz scale 69.54 and 84.6% (p ≤ 0.001), patients with high risk of capsule retention offered a patency capsule 4.2 and 73% (p ≤ 0.001), respectively. Conclusion: This study highlights and critically discusses technical and organizational issues that should be considered in defining more realistic PM thresholds, aiming to improve SBCE quality.


Introdução: A Sociedade Europeia de Endoscopia Digestiva (ESGE) identificou a necessidade de avaliar a qualidade da enteroscopia por videocápsula (EVC) e produziu um conjunto de medidas de desempenho (MD). O objetivo deste estudo é avaliar criticamente a concordância das medidas de desempenho de EVC em dois centros portugueses com diferentes plataformas de EVC. Métodos: Análise transversal de EVC consecutivas realizadas em 2 centros portugueses, com diferentes plataformas de EVC Mirocam® (IntroMedic, Seul, Coreia) e PillCam® (Medtronic, Yokneam, Israel), respetivamente. Um total de 10 medidas de desempenho (6 principais, 4 minor) foram avaliadas e comparadas entre os 2 centros. Resultados: Foram incluídas 493 EVC. O standard mínimo estabelecido pela ESGE foi alcançado em 3/6 MD principais (visualização completa, taxa de detecção de lesões e taxa de cápsula retida), e nenhum nas quatro MD minor. O cumprimento das MD diferiu significativamente entre os 2 centros: visualização completa do intestino delgado 95,9 e 90% (p = 0,01), taxa de deteção de lesões 50,6% e 63% (p = 0,005), adequada preparação do intestino delgado de acordo com a escala de Brotz 69,54 e 84,6% (p ≤ 0,001), doentes com alto risco de retenção da cápsula a quem foi oferecida cápsula de patência 4,2 e 73% (p ≤ 0,001), respectivamente. Introdução: Este estudo destaca e discute criticamente questões técnicas e organizacionais que devem ser consideradas na definição de limiares de MD mais realistas, com o objetivo de melhorar a qualidade da EVC.

11.
Echocardiography ; 40(6): 577-583, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-37150966

RESUMO

Subvalvular aortic stenosis manifesting as a subaortic membrane predisposes to bacterial endocarditis, which typically affects the aortic valve (AoV) or, less frequently, the left ventricular outflow tract (LVOT). We present the case of a 60-year-old woman expressing an odd form of a subvalvular aortic membrane in conjunction with a left Valsalva sinus pseudoaneurysm as a result of an endocarditis complication.


Assuntos
Estenose Aórtica Subvalvar , Estenose da Valva Aórtica , Endocardite Bacteriana , Endocardite , Feminino , Humanos , Pessoa de Meia-Idade , Valva Aórtica , Estenose Aórtica Subvalvar/complicações , Estenose da Valva Aórtica/complicações , Endocardite Bacteriana/complicações , Endocardite/complicações
12.
Proc Natl Acad Sci U S A ; 120(20): e2214853120, 2023 05 16.
Artigo em Inglês | MEDLINE | ID: mdl-37155874

RESUMO

Gastric cancer is a dominating cause of cancer-associated mortality with limited therapeutic options. Here, we show that syndecan-4 (SDC4), a transmembrane proteoglycan, is highly expressed in intestinal subtype gastric tumors and that this signature associates with patient poor survival. Further, we mechanistically demonstrate that SDC4 is a master regulator of gastric cancer cell motility and invasion. We also find that SDC4 decorated with heparan sulfate is efficiently sorted in extracellular vesicles (EVs). Interestingly, SDC4 in EVs regulates gastric cancer cell-derived EV organ distribution, uptake, and functional effects in recipient cells. Specifically, we show that SDC4 knockout disrupts the tropism of EVs for the common gastric cancer metastatic sites. Our findings set the basis for the molecular implications of SDC4 expression in gastric cancer cells and provide broader perspectives on the development of therapeutic strategies targeting the glycan-EV axis to limit tumor progression.


Assuntos
Neoplasias Gástricas , Sindecana-4 , Humanos , Heparitina Sulfato/metabolismo , Invasividade Neoplásica , Neoplasias Gástricas/genética , Sindecana-4/genética , Sindecana-4/metabolismo
14.
Glycoconj J ; 40(4): 421-433, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37074623

RESUMO

Expression of sialyl Lewis X (SLeX) is a well-documented event during malignant transformation of cancer cells, and largely associates with their invasive and metastatic properties. Glycoproteins and glycolipids are the main carriers of SLeX, whose biosynthesis is known to be performed by different glycosyltransferases, namely by the family of ß-galactoside-α2,3-sialyltransferases (ST3Gals). In this study, we sought to elucidate the role of ST3GalIV in the biosynthesis of SLeX and in malignant properties of gastrointestinal (GI) cancer cells. By immunofluorescent screening, we selected SLeX-positive GI cancer cell lines and silenced ST3GalIV expression via CRISPR/Cas9. Flow cytometry, immunofluorescence and western blot analysis showed that ST3GalIV KO efficiently impaired SLeX expression in most cancer cell lines, with the exception of the colon cancer cell line LS174T. The impact of ST3GalIV KO in the biosynthesis of SLeX isomer SLeA and non sialylated Lewis X and A were also evaluated and overall, ST3GalIV KO led to a decreased expression of SLeA and an increased expression in both LeX and LeA. In addition, the abrogation of SLeX on GI cancer cells led to a reduction in cell motility. Furthermore, ST3GalVI KO was performed in LS174T ST3GalIV KO cells, resulting in the complete abolishment of SLeX expression and consequent reduced motility capacity of those cells. Overall, these findings portray ST3GalIV as the main, but not the only, enzyme driving the biosynthesis of SLeX in GI cancer cells, with a functional impact on cancer cell motility.


Assuntos
Neoplasias do Colo , Humanos , Movimento Celular , Neoplasias do Colo/genética , Neoplasias do Colo/metabolismo , Glicolipídeos , Oligossacarídeos/metabolismo , Antígeno Sialil Lewis X
15.
GE Port J Gastroenterol ; 30(2): 134-140, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37008528

RESUMO

Background: Bowel preparation is a major quality criterion for colonoscopies. Models developed to identify patients with inadequate preparation have not been validated in external cohorts. We aim to validate these models and determine their applicability. Methods: Colonoscopies between April and November 2019 were retrospectively included. Boston Bowel Preparation Scale ≥2 per segment was considered adequate. Insufficient data, incomplete colonoscopies, and total colectomies were excluded. Two models were tested: model 1 (tricyclic antidepressants, opioids, diabetes, constipation, abdominal surgery, previous inadequate preparation, inpatient status, and American Society of Anesthesiology [ASA] score ≥3); model 2 (co-morbidities, tricyclic antidepressants, constipation, and abdominal surgery). Results: We included 514 patients (63% males; age 61.7 ± 15.6 years), 441 with adequate preparation. The main indications were inflammatory bowel disease (26.1%) and endoscopic treatment (24.9%). Previous surgery (36.2%) and ASA score ≥3 (23.7%) were the most common comorbidities. An ASA score ≥3 was the only identified predictor for inadequate preparation in this study (p < 0.001, OR 3.28). The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of model 1 were 60.3, 64.2, 21.8, and 90.7%, respectively. Model 2 had a sensitivity, specificity, PPV, and NPV of 57.5, 67.4, 22.6, and 90.5%, respectively. The AUC for the ROC curves was 0.62 for model 1, 0.62 for model 2, and 0.65 for the ASA score. Conclusions: Although both models accurately predict adequate bowel preparation, they are still unreliable in predicting inadequate preparation and, as such, new models, or further optimization of current ones, are needed. Utilizing the ASA score might be an appropriate approximation of the risk for inadequate bowel preparation in tertiary hospital populations.


Introdução: A preparação intestinal é um dos principais critérios de qualidade na colonoscopia. Modelos desenvolvidos para identificar doentes com preparação inadequada nunca foram validados em coortes externas. Pretendemos validar esses modelos e determinar sua aplicabilidade clínica. Métodos: Colonoscopias entre abril-novembro/2019 foram incluídas retrospectivamente. A Escala de Preparação Intestinal de Boston ≥2 por segmento foi considerada adequada. Dados insuficientes, colonoscopias incompletas e colectomias totais foram excluídos. Dois modelos foram testados: modelo 1 (antidepressivos tricíclicos, opióides, diabetes, obstipação, cirurgia abdominal, preparação prévia inadequada, internamento e American Society of Anesthesiology [ASA] ≥3); modelo 2 (comorbilidades, antidepressivos tricíclicos, obstipação e cirurgia abdominal). Resultados: Foram incluídos 514 doentes (63% homens; idade 61.7 ± 15.6), 441 com preparação adequada. As principais indicações foram doença inflamatória intestinal (26.1%) e tratamento endoscópico (24.9%). Cirurgias anteriores (36.2%) e ASA ≥3 (23.7%) foram as comorbilidades mais comuns. Um score ASA ≥3 foi o único fator de risco identificado para preparação inadequada (p < 0.001, OR 3.28). A sensibilidade, especificidade, valor preditivo positivo (VPP) e valor preditivo negativo (VPN) do modelo 1 foi de 60.3, 64.2, 21.8 e 90.7%. O modelo 2 apresentou sensibilidade, especificidade, VPP e VPN de 57.5, 67.4, 22.6 e 90.55%. A AUC para a curva ROC foi de 0.62 para o modelo 1, 0.62 para o modelo 2 e 0.65 para o score ASA. Conclusões: Embora ambos os modelos sejam eficazes a prever preparação intestinal adequada, não se verifica o mesmo para a preparação inadequada e como tal, novos modelos ou otimização dos atuais são ainda necessários. Utilizar o score ASA pode ser uma aproximação adequada do risco de preparação intestinal inadequada em populações de hospitais terciários.

17.
Front Endocrinol (Lausanne) ; 14: 1102068, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36926023

RESUMO

The involvement of immunity in psychiatric disorders, such as anxiety, is typified by the morphologic adaptation of microglia, immune cells of the brain, to anxiogenic stimuli. We previously reported sexually differentiated microglia morphology in adult rodents, in brain locations implicated in anxiety, including the pre-frontal cortex. These physiologic differences likely drive sex-dependent patterns of microglia morphologic remodeling in response to varied stress conditions in different periods of life, that correlate with sex-dependent behavioral adaptation to anxiogenic stimuli. The time-window of appearance of sex differences in microglia, correlating with sex-specific behavioral performance in anxiogenic conditions are still unknown. In rodents, a postnatal peak of the sexual hormone testosterone is determinant for the so-called brain masculinization and sex-determined behavioral traits. In the present work we aim to clarify if differences in microglia morphology are present at birth or can be driven by postnatal testosterone and impacts on the ability to deal with an anxiogenic context. Differences in microglia morphology are not present at birth, but are observable at adolescence (increased complexity of male microglia, particularly in branches more proximal to the soma), when differences in behavior are also observed. Our data also show that adolescent females neonatally treated with testosterone exhibit masculinized microglia and behavior. Importantly, between adolescence and adulthood, a sex-determined shift in the pattern of complexity takes place and microglia from females become more complex. When testosterone is administered, this morphological effect is partially abolished, approximating microglia and behavior to the male phenotype.


Assuntos
Microglia , Testosterona , Animais , Feminino , Masculino , Testosterona/farmacologia , Comportamento Animal , Comportamento Sexual Animal , Encéfalo/fisiologia
18.
Cureus ; 15(2): e35324, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36994248

RESUMO

PURPOSE: Polypharmacy in cancer patients is a recognized issue and should be an integral part of comprehensive patient assessment and management. Despite this, a systematic review of concomitant drugs or a search for potential drug-drug interactions (DDIs) is not always performed. Here, we present the results of a medication reconciliation model performed by a multidisciplinary team to identify clinically meaningful potential DDIs (defined by the presence of DDI of major severity or contraindication) in cancer patients undergoing oral antineoplastic drugs. METHODS: From June to December 2022, we performed a non-interventional, prospective, cross-sectional, single-center study of adult cancer patients, initiating or undergoing treatment with oral antineoplastic drugs, referred by their oncologists for therapeutic review regarding potential DDIs. DDIs were assessed by a multidisciplinary team of hospital pharmacists and medical oncologists, through research in three different drug databases as well as in the summary of product characteristics. A report detailing all potential DDIs was created for each request and provided to the patient's medical oncologist for further examination. RESULTS: Overall, 142 patients' medications were reviewed. Regardless of the severity or clinical importance, 70.4% of patients had at least one potential DDI. We found 184 combinations of oral anticancer and regular therapy agents with potential DDIs, 55 of whom were considered of major severity by at least one DDI database. As expected, the number of potential DDIs increased with the number of active substances in regular therapy (p < 0.001), but we did not find an increased relation between age and the total number of potential DDIs (p = 0.109). Thirty-nine (27.5%) patients had at least one clinically meaningful DDI identified. After adjustment through multivariable logistic regression, only the female sex (odds ratio (OR) 3.01, p = 0.029), the number of active comorbidities (OR 0.60, p = 0.029), and the presence of proton pump inhibitors in chronic medication (OR 2.99, p = 0.033) remained as predictors of potential meaningful DDI. CONCLUSION: Although drug interactions are a concern in oncology, a systematic DDI review is rarely conducted in medical oncology consultations. The availability of a medication reconciliation service, carried out by a multidisciplinary team with dedicated time for this task, is an added value for safety enhancement in cancer patients.

20.
Polymers (Basel) ; 15(2)2023 Jan 12.
Artigo em Inglês | MEDLINE | ID: mdl-36679277

RESUMO

The purpose of this study was to evaluate the color changes of feldspathic ceramics CEREC Blocs (Dentsply Sirona, Milford, DE, USA) when cemented with different luting agents, while varying the ceramic thickness. Seventy ceramic discs of feldspathic ceramic (A2 shade) were obtained with 0.5 and 0.8 mm thicknesses. Seventy composite discs (A3 shade) 1 mm in thickness were used as substrates. After being polished and conditioned, the ceramic and composite discs were cemented with different resin cements and a flowable composite: Variolink® Esthetic Light, Neutral and Warm (Ivoclar Vivadent, Schaan, Liechtenstein); RelyXTM Veneer B0.5, Translucent and A3 Opaque/yellow shades (3M Oral Care, St. Paul, MN, USA); G-aenial® Universal Flow A2 (GC Europe, Leuven, Belgium). Color difference (ΔE) was determined using a spectrophotometer. A two-way ANOVA and multiple comparisons were performed using the Bonferroni method with a 95% confidence interval. Variolink® Neutral showed the highest ΔE (15.12 ± 0.71) and RelyXTM Veneer A3 the lowest value (1.59 ± 0.33). There are no statistically significant differences between the two ceramic thicknesses for Variolink® Light (p = 0.230) and RelyXTM Veneer B0.5 (p = 0.318) cements. The feldspathic ceramic final color is influenced by the cement used and the ceramic thickness. The use of different cements in a thin ceramic has a clinically significant impact on the final esthetic result.

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