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1.
Mov Disord ; 39(10): 1843-1855, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-39051491

RESUMO

BACKGROUND: Parkinson's disease (PD) is the second most common neurodegenerative disease following Alzheimer's disease. Nearly 30 causative genes have been identified for PD and related disorders. However, most of these genes were identified in European-derived families, and little is known about their role in Latin American populations. OBJECTIVES: Our goal was to assess the spectrum and frequency of pathogenic variants in known PD genes in familial PD patients from Latin America. METHODS: We selected 335 PD patients with a family history of PD from the Latin American Research Consortium on the Genetics of PD. We capture-sequenced the coding regions of 26 genes related to neurodegenerative parkinsonism. Of the 335 PD patients, 324 had sufficient sequencing coverage to be analyzed. RESULTS: We identified pathogenic variants in 41 individuals (12.7%) in FBXO7, GCH1, LRRK2, PARK7, PINK1, PLA2G6, PRKN, SNCA, and TARDBP, GBA1 risk variants in 25 individuals (7.7%), and variants of uncertain significance in another 24 individuals (7.4%) in ATP13A2, ATP1A3, DNAJC13, DNAJC6, GBA1, LRKK2, PINK1, VPS13C, and VPS35. Of the 70 unique variants identified, 19 were more frequent in Latin Americans than in any other population. CONCLUSIONS: This is the first screening of known PD genes in a large cohort of patients with familial PD from Latin America. There were substantial differences in the spectrum of variants observed in comparison to previous findings from PD families of European origin. Our data provide further evidence that differences exist between the genetic architecture of PD in Latinos and European-derived populations. © 2024 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.


Assuntos
Testes Genéticos , Doença de Parkinson , Humanos , Doença de Parkinson/genética , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Testes Genéticos/métodos , América do Sul , América Central , Predisposição Genética para Doença/genética , Adulto
2.
Comput Methods Programs Biomed ; 254: 108296, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-38941860

RESUMO

BACKGROUND AND OBJECTIVE: In this work, the analysis of the importance of hemodynamic updates on a mechanobiological model of atheroma plaque formation is proposed. METHODS: For that, we use an idealized and axisymmetric model of carotid artery. In addition, the behavior of endothelial cells depending on hemodynamical changes is analyzed too. A total of three computational simulations are carried out and their results are compared: an uncoupled model and two models that consider the opposite behavior of endothelial cells caused by hemodynamic changes. The model considers transient blood flow using the Navier-Stokes equation. Plasma flow across the endothelium is determined with Darcy's law and the Kedem-Katchalsky equations, considering the three-pore model, which is also employed for the flow of substances across the endothelium. The behavior of the considered substances in the arterial wall is modeled with convection-diffusion-reaction equations, and the arterial wall is modeled as a hyperelastic Yeoh's material. RESULTS: Significant variations are noted in both the morphology and stenosis ratio of the plaques when comparing the uncoupled model to the two models incorporating updates for geometry and hemodynamic stimuli. Besides, the phenomenon of double-stenosis is naturally reproduced in the models that consider both geometric and hemodynamical changes due to plaque growth, whereas it cannot be predicted in the uncoupled model. CONCLUSIONS: The findings indicate that integrating the plaque growth model with geometric and hemodynamic settings is essential in determining the ultimate shape and dimensions of the carotid plaque.


Assuntos
Aterosclerose , Artérias Carótidas , Simulação por Computador , Hemodinâmica , Modelos Cardiovasculares , Humanos , Aterosclerose/fisiopatologia , Artérias Carótidas/fisiopatologia , Placa Aterosclerótica/fisiopatologia , Células Endoteliais , Estresse Mecânico , Fenômenos Biomecânicos , Endotélio Vascular/fisiopatologia
3.
Front Sports Act Living ; 6: 1335258, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38774279

RESUMO

Although whistleblowing is thought to represent an effective mechanism for detecting and uncovering doping in sport, it has yet to become a widely adopted practice. Understanding the factors that encourage or discourage whistleblowing is of vital importance for the promotion of this practice and the development of pedagogical material to enhance the likelihood of whistleblowing. The current study employed a qualitative methodology to explore the personal and organisational factors that underpin intentions to blow the whistle or that may lead to engagement in whistleblowing behaviours in sport. Thirty-three competitive athletes across a range of sports took part in a semi-structured interview which sought to explore what they would do should they encounter a doping scenario. Content analysis revealed that whistleblowing is a dynamic process characterised by the interaction of a range of personal and organisational factors in determining the intention to report PED use. These factors included moral reasoning, a desire to keep the matter "in-house", perceived personal costs, institutional attitudes to doping, and social support. Analysis revealed a number of "intervening events", including a perceived lack of organisational protection (e.g., ethical leadership) within some sporting sub-cultures, which present an important obstacle to whistleblowing. The intention to report doping was underpinned by a "fairness-loyalty trade-off" which involved athletes choosing to adhere to either fairness norms (which relate to a sense that all people and groups are treated equally) or loyalty norms (which reflect preferential treatment towards an in-group) when deciding whether they would blow the whistle. The promotion of fairness norms that emphasise a group's collective interests might encourage athletes to view whistleblowing as a means of increasing group cohesiveness and effectiveness and thereby increase the likelihood of this practice.

4.
PeerJ Comput Sci ; 10: e1898, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38660188

RESUMO

Data privacy is one of the biggest challenges facing system architects at the system design stage. Especially when certain laws, such as the General Data Protection Regulation (GDPR), have to be complied with by cloud environments. In this article, we want to help cloud providers comply with the GDPR by proposing a GDPR-compliant cloud architecture. To do this, we use model-driven engineering techniques to design cloud architecture and analyze cloud interactions. In particular, we develop a complete framework, called MDCT, which includes a Unified Modeling Language profile that allows us to define specific cloud scenarios and profile validation to ensure that certain required properties are met. The validation process is implemented through the Object Constraint Language (OCL) rules, which allow us to describe the constraints in these models. To comply with many GDPR articles, the proposed cloud architecture considers data privacy and data tracking, enabling safe and secure data management and tracking in the context of the cloud. For this purpose, sticky policies associated with the data are incorporated to define permission for third parties to access the data and track instances of data access. As a result, a cloud architecture designed with MDCT contains a set of OCL rules to validate it as a GDPR-compliant cloud architecture. Our tool models key GDPR points such as user consent/withdrawal, the purpose of access, and data transparency and auditing, and considers data privacy and data tracking with the help of sticky policies.

5.
Polymers (Basel) ; 16(4)2024 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-38399906

RESUMO

The main advantage of green composites is their biodegradability, but this biodegradability can also be considered a drawback if the degradation appears during the service life of the component. Therefore, the study of the mechanical behavior of green composites after hygrothermal aging tests is necessary to analyze their degradation process. This study aims to comprehensively analyze the hygrothermal aging behavior and aging mechanism of flax-fiber-reinforced polylactic acid (PLA) biocomposites. The fully biodegradable composites are manufactured by compression molding. In addition, the influence of atmospheric-pressure plasma treatment on the mechanical properties of the biocomposite is studied. Specimens are exposed to water vapor and 40 °C environmental conditions in a stove for up to 42 days. Several specimens of each type are taken out at regular intervals and tested to examine the water absorption, mechanical properties, and thermal characterization. The results show that the stiffness was significantly reduced after 24 h due to matrix degradation, while the strength was reduced only after three weeks.

6.
ACS Biomater Sci Eng ; 10(2): 987-997, 2024 02 12.
Artigo em Inglês | MEDLINE | ID: mdl-38234159

RESUMO

A combination of human-induced pluripotent stem cells (hiPSCs) and 3D microtissue culture techniques allows the generation of models that recapitulate the cardiac microenvironment for preclinical research of new treatments. In particular, spheroids represent the simplest approach to culture cells in 3D and generate gradients of cellular access to the media, mimicking the effects of an ischemic event. However, previous models required incubation under low oxygen conditions or deprived nutrient media to recreate ischemia. Here, we describe the generation of large spheroids (i.e., larger than 500 µm diameter) that self-induce an ischemic core. Spheroids were generated by coculture of cardiomyocytes derived from hiPSCs (hiPSC-CMs) and primary human cardiac fibroblast (hCF). In the proper medium, cells formed aggregates that generated an ischemic core 2 days after seeding. Spheroids also showed spontaneous cellular reorganization after 10 days, with hiPSC-CMs located at the center and surrounded by hCFs. This led to an increase in microtissue stiffness, characterized by the implementation of a constriction assay. All in all, these phenomena are hints of the fibrotic tissue remodeling secondary to a cardiac ischemic event, thus demonstrating the suitability of these spheroids for the modeling of human cardiac ischemia and its potential application for new treatments and drug research.


Assuntos
Isquemia Miocárdica , Miócitos Cardíacos , Humanos , Constrição , Células Cultivadas , Isquemia
7.
Front Bioeng Biotechnol ; 11: 1304278, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38152285

RESUMO

Atherosclerosis is a prevalent cause of acute coronary syndromes that consists of lipid deposition inside the artery wall, creating an atherosclerotic plaque. Early detection may prevent the risk of plaque rupture. Nowadays, intravascular ultrasound (IVUS) is the most common medical imaging technology for atherosclerotic plaque detection. It provides an image of the section of the coronary wall and, in combination with new techniques, can estimate the displacement or strain fields. From these magnitudes and by inverse analysis, it is possible to estimate the mechanical properties of the plaque tissues and their stress distribution. In this paper, we presented a methodology based on two approaches to characterize the mechanical properties of atherosclerotic tissues. The first approach estimated the linear behavior under particular pressure. In contrast, the second technique yielded the non-linear hyperelastic material curves for the fibrotic tissues across the complete physiological pressure range. To establish and validate this method, the theoretical framework employed in silico models to simulate atherosclerotic plaques and their IVUS data. We analyzed different materials and real geometries with finite element (FE) models. After the segmentation of the fibrotic, calcification, and lipid tissues, an inverse FE analysis was performed to estimate the mechanical response of the tissues. Both approaches employed an optimization process to obtain the mechanical properties by minimizing the error between the radial strains obtained from the simulated IVUS and those achieved in each iteration. The second methodology was successfully applied to five distinct real geometries and four different fibrotic tissues, getting median R 2 of 0.97 and 0.92, respectively, when comparing the real and estimated behavior curves. In addition, the last technique reduced errors in the estimated plaque strain field by more than 20% during the optimization process, compared to the former approach. The findings enabled the estimation of the stress field over the hyperelastic plaque tissues, providing valuable insights into its risk of rupture.

8.
Artif Cells Nanomed Biotechnol ; 51(1): 466-475, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37665604

RESUMO

Tissue barrier permeability plays a crucial role in determining the selective transport of substances across epithelial tissues, including drugs, cosmetic substances, and chemicals. The ability of these substances to cross through tissue barriers affects their absorption into the bloodstream and ultimately their effectiveness. Therefore, the determination of their permeability on these type of tissue barriers represents a useful tool for pharmaceutical and cosmetic industries as well as for toxicological studies.In this regard, microfluidic devices and organ-on-chip technologies are becoming more important to generate reliable data. We have designed and performed an alternative new stratified epithelia-on-chip model that allows to correlate the Stokes radius and the diffusion of molecules and/or nanoformulations through the in vitro generated barrier and establish a system suitable for the analysis of diffusion through stratified epithelium. Thus, extrapolating from experimental data we can predict the Stokes radius for unknown fluorescent labelled particles within a molecular size range, such as gold nanoparticles.


Assuntos
Nanopartículas Metálicas , Rádio (Anatomia) , Ouro , Permeabilidade , Epitélio
9.
Cureus ; 15(9): e44955, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37701169

RESUMO

Renal cell carcinoma (RCC) is rarely diagnosed during pregnancy and its management represents a challenge as it necessitates considerations for the well-being of both the mother and the developing fetus. Diagnosis can be challenging and is often an incidental finding during routine imaging, which can lead to difficult decision-making. The choice of the ideal imaging study in these cases is a matter of debate. When the tumor is detected at an early stage, radical nephrectomy is indicated. However, there is still controversy regarding whether it should be performed conventionally or laparoscopically, as both techniques have their risks and benefits. In this context, our primary objective was to provide adequate surgical treatment for the patient, while safeguarding fetal health. Here, we present a patient with a history of recurrent miscarriages, in whom a renal tumor was incidentally diagnosed during pregnancy. Adding to the uniqueness of this case, the patient was diagnosed with an eosinophilic variant of chromophobe RCC through histopathological analysis. Our aim is to highlight the controversies surrounding diagnostic and treatment methodologies and to present the surgical techniques employed in this unique situation. This case underscores the importance and need for a multidisciplinary approach, which, in our instance, resulted in favorable outcomes for both maternal and neonatal health.

10.
J Patient Cent Res Rev ; 10(3): 111-120, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37483554

RESUMO

Purpose: The study purpose was to learn and describe 1) where homeless shelter residents receive health care, 2) what contributes to positive or negative health care experiences among shelter residents, and 3) shelter resident perceptions toward health care. Methods: Semi-structured interviews (SSIs) utilizing purposive sampling and focus group discussions (FGDs) utilizing convenience sampling were conducted at 6 homeless shelters in Seattle-King County, Washington, during July-October 2021. All residents (age ≥18) were eligible to participate. SSIs were conducted with 25 residents, and 8 FGDs were held. Thematic analysis was conducted using Dedoose. Results: Participants received health care in settings ranging from no regular care to primary care providers. Four elements emerged as contributing positively and negatively to health care experiences: 1) ability to access health care financially, physically, and technologically; 2) clarity of communication from providers and staff about appointment logistics, diagnoses, and treatment options; 3) ease of securing timely follow-up services; and 4) respect versus stigma and discrimination from providers and staff. Participants who felt positively toward health care found low- or no-cost care to be widely available and encouraged others to seek care. However, some participants described health care in the United States as greedy, classist, discriminatory, and untrustworthy. Participants reported delaying care and self-medicating in anticipation of discrimination. Conclusions: Findings demonstrate that while people experiencing homelessness can have positive experiences with health care, many have faced negative interactions with health systems. Improving the patient experience for those experiencing homelessness can increase engagement and improve health outcomes.

11.
Influenza Other Respir Viruses ; 17(1): e13092, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36610058

RESUMO

BACKGROUND: Persons experiencing homelessness face increased risk of influenza as overcrowding in congregate shelters can facilitate influenza virus spread. Data regarding on-site influenza testing and antiviral treatment within homeless shelters remain limited. METHODS: We conducted a cluster-randomized stepped-wedge trial of point-of-care molecular influenza testing coupled with antiviral treatment with baloxavir or oseltamivir in residents of 14 homeless shelters in Seattle, WA, USA. Residents ≥3 months with cough or ≥2 acute respiratory illness (ARI) symptoms and onset <7 days were eligible. In control periods, mid-nasal swabs were tested for influenza by reverse transcription polymerase chain reaction (RT-PCR). The intervention period included on-site rapid molecular influenza testing and antiviral treatment for influenza-positives if symptom onset was <48 h. The primary endpoint was monthly influenza virus infections in the control versus intervention periods. Influenza whole genome sequencing was performed to assess transmission and antiviral resistance. RESULTS: During 11/15/2019-4/30/2020 and 11/2/2020-4/30/2021, 1283 ARI encounters from 668 participants were observed. Influenza virus was detected in 51 (4%) specimens using RT-PCR (A = 14; B = 37); 21 influenza virus infections were detected from 269 (8%) intervention-eligible encounters by rapid molecular testing and received antiviral treatment. Thirty-seven percent of ARI-participant encounters reported symptom onset < 48 h. The intervention had no effect on influenza virus transmission (adjusted relative risk 1.73, 95% confidence interval [CI] 0.50-6.00). Of 23 influenza genomes, 86% of A(H1N1)pdm09 and 81% of B/Victoria sequences were closely related. CONCLUSION: Our findings suggest feasibility of influenza test-and-treat strategies in shelters. Additional studies would help discern an intervention effect during periods of increased influenza activity.


Assuntos
Pessoas Mal Alojadas , Vírus da Influenza A Subtipo H1N1 , Influenza Humana , Infecções por Orthomyxoviridae , Humanos , Influenza Humana/diagnóstico , Influenza Humana/tratamento farmacológico , Influenza Humana/epidemiologia , Vírus da Influenza A Subtipo H1N1/genética , Oseltamivir/uso terapêutico , Antivirais/uso terapêutico , Infecções por Orthomyxoviridae/tratamento farmacológico
12.
PeerJ Comput Sci ; 8: e1171, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36532816

RESUMO

This article presents a tool called GDPRValidator that aims to assist small and medium-sized enterprises (SMEs) that have migrated their services, or a part of them, to the cloud to be General Data Protection Regulation (GDPR) compliant when they manage and store employees' or customers' data in the cloud. As these companies have a limited budget to hire legal experts to guide them in complying with GDPR, the main objective of this tool is to help SMEs to be more competitive by saving a considerable amount of money. By using GDPRValidator, these companies can learn and begin the GDPR compliance process by themselves and decide whether it will be necessary to hire GDPR legal experts in the end. GDPRValidator implements a process that aids companies in compliance analysis and validation and generates a series of documents with recommendations. These documents do not guarantee full GDPR compliance, but they can help the company better understand the regulation and improve its data management strategies. In order to validate the efficiency and efficacy of the tool, two SMEs have used it and provided feedback about its perceived ease of use and its perceived usefulness for understanding and complying with GDPR. The results of the validation showed that, for both companies, the degree of perceived usefulness and ease of use of GDPRValidator is quite good. All the scores expressed agreement.

13.
Polymers (Basel) ; 14(22)2022 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-36433052

RESUMO

This work provides a structural analysis of small-scale 3D-printed wind turbine ribs subjected to compression. The ribs were manufactured according to NACA 23015 and NACA 633618 geometries, with polylactic acid (PLA) and polylactic acid with carbon fiber additives (CF-PLA). In addition, holes were manufactured into the sample bodies by either 3D printing or drilling for being compared with solid samples. The compression testing was performed by following the ASTM 695D standard, whereas the beginning and propagation of delamination were assessed with the ASTM 5528 standard. Experimental results revealed that 3D-printed built-in holes provided higher compression strength, hence higher structural efficiency, than the drilled samples. Significant improvement by adding carbon fiber additives into the PLA resin system in comparison to raw PLA was detected for at least one of the studied airfoil profiles. NACA geometries also represented a key parameter for avoiding stress concentration areas, as the FEM modeling supported. However, in damaged areas, fracture mechanisms were observed such as bead-bridging, which is a key parameter in reinforcing and consolidating the specimen bodies. Working in better interphase bonding and different additives between beads and layers is highly suggested for future studies.

14.
Int J Pharm ; 620: 121742, 2022 May 25.
Artigo em Inglês | MEDLINE | ID: mdl-35427751

RESUMO

The most common treatment for obstructive coronary artery disease (CAD) is the implantation of a permanent drug-eluting stent (DES). Not only has this permanency been associated with delayed healing of the artery, but it also poses challenges when treating subsequent re-narrowing due to in-stent restenosis (ISR). Drug-coated balloons (DCBs) provide a potential solution to each of these issues. While their use has been primarily limited to treating ISR, in recent years, DCBs have emerged as an attractive potential alternative to DESs for the treatment of certain de novo lesions. However, there remain a number of concerns related to the safety and efficacy of these devices. Firstly, unlike DESs, DCBs necessitate a very short drug delivery window, favouring a higher drug loading. Secondly, while the majority of coronary DCBs in Europe are coated with paclitaxel, the potential mortality signal raised with paclitaxel DCBs in peripheral interventions has shifted efforts towards the development of limus-eluting balloons. The purpose of this paper is to provide a computational model that allows drug delivery from DCBs and DESs to be investigated and compared. We present a comprehensive computational framework that employs a 2D-axisymmetric geometry, incorporates two nonlinear phases of drug binding (specific and non-specific) and includes the influence of diffusion and advection, within a multilayer arterial wall. We utilise this framework to (i) simulate drug delivery from different types of balloon platform; (ii) explore the influence of DCB application time; (iii) elucidate the importance on release kinetics of elevated pressure during DCB application; (iv) compare DCB delivery of two different drugs (sirolimus and paclitaxel) and; (v) compare simulations of DESs versus DCBs. Key measures of comparison are related to safety (drug content in tissue, DC) and efficacy (specific binding site saturation, %SBSS) markers. Our results highlight the pros and cons of each device in terms of DC and %SBSS levels achieved and, moreover, indicate the potential for designing a DCB that gives rise to sufficiently similar safety and efficacy indicators as current commercial DESs.


Assuntos
Doença da Artéria Coronariana , Stents Farmacológicos , Materiais Revestidos Biocompatíveis , Doença da Artéria Coronariana/terapia , Humanos , Paclitaxel , Sirolimo , Stents , Resultado do Tratamento
15.
Sensors (Basel) ; 22(7)2022 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-35408236

RESUMO

Multiple fault identification in induction motors is essential in industrial processes due to the high costs that unexpected failures can cause. In real cases, the motor could present multiple faults, influencing systems that classify isolated failures. This paper presents a novel methodology for detecting multiple motor faults based on quaternion signal analysis (QSA). This method couples the measured signals from the motor current and the triaxial accelerometer mounted on the induction motor chassis to the quaternion coefficients. The QSA calculates the quaternion rotation and applies statistics such as mean, variance, kurtosis, skewness, standard deviation, root mean square, and shape factor to obtain their features. After that, four classification algorithms are applied to predict motor states. The results of the QSA method are validated for ten classes: four single classes (healthy condition, unbalanced pulley, bearing fault, and half-broken bar) and six combined classes. The proposed method achieves high accuracy and performance compared to similar works in the state of the art.


Assuntos
Algoritmos , Indústrias
16.
ISME J ; 16(7): 1798-1808, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-35396347

RESUMO

Lost Hammer Spring, located in the High Arctic of Nunavut, Canada, is one of the coldest and saltiest terrestrial springs discovered to date. It perennially discharges anoxic (<1 ppm dissolved oxygen), sub-zero (~-5 °C), and hypersaline (~24% salinity) brines from the subsurface through up to 600 m of permafrost. The sediment is sulfate-rich (1 M) and continually emits gases composed primarily of methane (~50%), making Lost Hammer the coldest known terrestrial methane seep and an analog to extraterrestrial habits on Mars, Europa, and Enceladus. A multi-omics approach utilizing metagenome, metatranscriptome, and single-amplified genome sequencing revealed a rare surface terrestrial habitat supporting a predominantly lithoautotrophic active microbial community driven in part by sulfide-oxidizing Gammaproteobacteria scavenging trace oxygen. Genomes from active anaerobic methane-oxidizing archaea (ANME-1) showed evidence of putative metabolic flexibility and hypersaline and cold adaptations. Evidence of anaerobic heterotrophic and fermentative lifestyles were found in candidate phyla DPANN archaea and CG03 bacteria genomes. Our results demonstrate Mars-relevant metabolisms including sulfide oxidation, sulfate reduction, anaerobic oxidation of methane, and oxidation of trace gases (H2, CO2) detected under anoxic, hypersaline, and sub-zero ambient conditions, providing evidence that similar extant microbial life could potentially survive in similar habitats on Mars.


Assuntos
Metano , Microbiota , Anaerobiose , Archaea/genética , Archaea/metabolismo , Gases/metabolismo , Sedimentos Geológicos/microbiologia , Metano/metabolismo , Oxirredução , Oxigênio/metabolismo , Filogenia , RNA Ribossômico 16S/genética , Sulfatos/metabolismo , Sulfetos/metabolismo
17.
Front Oncol ; 12: 835626, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35433488

RESUMO

Purposes: Most molecular-based published studies on breast cancer do not adequately represent the unique and diverse genetic admixture of the Latin American population. Searching for similarities and differences in molecular pathways associated with these tumors and evaluating its impact on prognosis may help to select better therapeutic approaches. Patients and Methods: We collected clinical, pathological, and transcriptomic data of a multi-country Latin American cohort of 1,071 stage II-III breast cancer patients of the Molecular Profile of Breast Cancer Study (MPBCS) cohort. The 5-year prognostic ability of intrinsic (transcriptomic-based) PAM50 and immunohistochemical classifications, both at the cancer-specific (OSC) and disease-free survival (DFS) stages, was compared. Pathway analyses (GSEA, GSVA and MetaCore) were performed to explore differences among intrinsic subtypes. Results: PAM50 classification of the MPBCS cohort defined 42·6% of tumors as LumA, 21·3% as LumB, 13·3% as HER2E and 16·6% as Basal. Both OSC and DFS for LumA tumors were significantly better than for other subtypes, while Basal tumors had the worst prognosis. While the prognostic power of traditional subtypes calculated with hormone receptors (HR), HER2 and Ki67 determinations showed an acceptable performance, PAM50-derived risk of recurrence best discriminated low, intermediate and high-risk groups. Transcriptomic pathway analysis showed high proliferation (i.e. cell cycle control and DNA damage repair) associated with LumB, HER2E and Basal tumors, and a strong dependency on the estrogen pathway for LumA. Terms related to both innate and adaptive immune responses were seen predominantly upregulated in Basal tumors, and, to a lesser extent, in HER2E, with respect to LumA and B tumors. Conclusions: This is the first study that assesses molecular features at the transcriptomic level in a multicountry Latin American breast cancer patient cohort. Hormone-related and proliferation pathways that predominate in PAM50 and other breast cancer molecular classifications are also the main tumor-driving mechanisms in this cohort and have prognostic power. The immune-related features seen in the most aggressive subtypes may pave the way for therapeutic approaches not yet disseminated in Latin America. Clinical Trial Registration: ClinicalTrials.gov (Identifier: NCT02326857).

18.
J Biomech ; 132: 110909, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-35032837

RESUMO

We analyze the residual stresses and mechanical properties of layer-dissected infrarenal abdominal aorta (IAA). We measured the axial pre-stretch and opening angle and performed uniaxial tests to study and compare the mechanical behavior of both intact and layer-dissected porcine IAA samples under physiological loads. Finally, some of the most popular anisotropic hyperelastic constitutive models (GOH and microfiber models) were proposed to estimate the mechanical properties of the abdominal aorta by least-square fitting of the recorded in-vitro uniaxial test results. The results show that the residual stresses are layer dependent. In all cases, we found that the OA in the media layer is lower than in the whole artery, the intima and the adventitia. For the axial pre-stretch, we found that the adventitia and the media were slightly stretched in the environment of the intact arterial strip, whereas the intima appears to be compressed. Regarding the mechanical properties, the media seems to be the softest layer over the whole deformation domain showing high anisotropy, while the intima and adventitia exhibit considerable stiffness and a lower anisotropy response. Finally, all the hyperelastic anisotropic models considered in this study provided a reasonable approximation of the experimental data. The GOH model showed the best fitting.


Assuntos
Túnica Adventícia , Aorta Abdominal , Túnica Adventícia/fisiologia , Animais , Anisotropia , Fenômenos Biomecânicos , Estresse Mecânico , Suínos
19.
Bol. méd. Hosp. Infant. Méx ; 78(4): 265-272, Jul.-Aug. 2021. tab, graf
Artigo em Inglês | LILACS-Express | LILACS | ID: biblio-1345411

RESUMO

Abstract Background: Vitamin D (VD) deficiency has been inversely associated with parathyroid hormone (PTH) levels in the adult population but not in children and adolescents. This study aimed to report VD concentration and its correlation with PTH levels in a sample of healthy Mexican children. Methods: We conducted a cross-sectional study with 275 healthy Mexican subjects aged 2 to 17 years to estimate the status of 25-(OH)-D and its correlation with PTH levels. The 25-(OH)-D levels were estimated by liquid chromatography-tandem mass spectrometry and PTH by radioimmunoassay. Results: Subjects were categorized as young children (2 to 5 years), school children (6 to 10 years), and adolescents (11 to 17 years). The median concentration of 25-(OH)-D in young children was 27.4 ng/ml; in school children, 25.6 ng/ml; and adolescents, 24.7 ng/ml. VD levels < 20 ng/ml were found in only 10.5% of the participants. Only 3% of the young children showed VD deficiency, in contrast to 10% of school children and 21% of adolescents (p ≤ 0.05). PTH was found within normal ranges in 95.6% of the studied population. VD levels < 20 mg/dl were found in 25.8% of children with overweight or obesity (p = 0.009). Conclusions: VD levels < 20 ng/ml were observed in 10% of the studied group, but this percentage increased with age: 21% of the adolescents showed VD levels < 20 ng/ml. No correlation with PTH levels was found. The VD values reported in this study are lower than those previously reported in Mexican children.


Resumen Introducción: La deficiencia de vitamina D se ha asociado inversamente con la concentración de hormona paratiroidea (PTH) en los adultos, pero no en los niños y adolescentes. El objetivo de este estudio fue reportar la concentración de vitamina D y su correlación con la concentración de PTH en una muestra de niños mexicanos sanos. Métodos: Se llevó a cabo un estudio transversal con 275 mexicanos sanos de 2 a 17 años de edad en quienes se estimaron las concentraciones de 25-(OH)-D utilizando cromatografía líquida con espectrometría de masas y de PTH por radioinmunoensayo, y su correlación. Resultados: Los participantes se categorizaron como prescolares (2 a 5 años), escolares (6 a 10 años) y adolescentes (11 a 17 años). La mediana de la concentración de 25-(OH)-D en los prescolares fue de 27.4 ng/ml, en los escolares de 25.6 ng/ml y en los adolescentes de 24.7 ng/ml. Solo en el 10.5% de los participantes se encontraron valores de vitamina D < 20 ng/ml. En contraste con el 10% de los escolares y el 21% de los adolescentes, solo el 3% de los prescolares mostraron deficiencia de vitamina D (p ≤ 0.05). La PTH se encontró dentro de los límites normales en el 95.6% de la población estudiada. Se encontraron concentraciones de vitamina D < 20 mg/dl en el 25.8% de los niños con sobrepeso y obesidad (p = 0.009). Conclusiones: Solo en el 10% de los participantes se encontraron concentraciones de vitamina D < 20 ng/ml, pero este porcentaje aumento con la edad y se hallaron valores < 20 ng/ml en el 21% de los adolescentes. La PTH se encontró dentro de los valores normales. Las concentraciones de vitamina D en este estudio resultaron menores que las previamente reportadas en niños mexicanos.

20.
Bol Med Hosp Infant Mex ; 78(4): 265-272, 2021 06 09.
Artigo em Inglês | MEDLINE | ID: mdl-34107534

RESUMO

BACKGROUND: Vitamin D (VD) deficiency has been inversely associated with parathyroid hormone (PTH) levels in the adult population but not in children and adolescents. This study aimed to report VD concentration and its correlation with PTH levels in a sample of healthy Mexican children. METHODS: We conducted a cross-sectional study with 275 healthy Mexican subjects aged 2 to 17 years to estimate the status of 25-(OH)-D and its correlation with PTH levels. The 25-(OH)-D levels were estimated by liquid chromatography-tandem mass spectrometry and PTH by radioimmunoassay. RESULTS: Subjects were categorized as young children (2 to 5 years), school children (6 to 10 years), and adolescents (11 to 17 years). The median concentration of 25-(OH)-D in young children was 27.4 ng/ml; in school children, 25.6 ng/ml; and adolescents, 24.7 ng/ml. VD levels < 20 ng/ml were found in only 10.5% of the participants. Only 3% of the young children showed VD deficiency, in contrast to 10% of school children and 21% of adolescents (p ≤ 0.05). PTH was found within normal ranges in 95.6% ofthe studied population. VD levels < 20 mg/dl were found in 25.8% of children with overweight or obesity (p = 0.009). CONCLUSIONS: VD levels < 20 ng/ml were observed in 10% of the studied group, but this percentage increased with age:21% of the adolescents showed VD levels < 20 ng/ml. No correlation with PTH levels was found. The VD values reported inthis study are lower than those previously reported in Mexican children.


Assuntos
Deficiência de Vitamina D , Vitamina D , Adolescente , Adulto , Criança , Pré-Escolar , Estudos Transversais , Humanos , Obesidade , Hormônio Paratireóideo , Deficiência de Vitamina D/epidemiologia
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