Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 86
Filtrar
1.
Cureus ; 16(6): e61876, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38975555

RESUMO

Influenza B infection, although primarily recognized for respiratory symptoms, can lead to rare but severe cardiac complications such as pericardial effusion and cardiac tamponade. We present a case of a 33-year-old female with morbid obesity who initially exhibited flu-like symptoms, was subsequently diagnosed with influenza B infection, and was discharged with symptomatic treatment. Despite initial discharge, she returned with worsening weakness, gastrointestinal symptoms, and shortness of breath. Imaging studies confirmed pericardial effusion with early signs of tamponade, necessitating an emergent intervention. The patient underwent subxiphoid pericardial window and fluid removal, followed by colchicine treatment to prevent recurrence. Our case highlights the importance of recognizing and promptly managing rare influenza-related complications, particularly in patients without significant comorbidities. It underscores the value of a proactive approach, utilizing point-of-care ultrasound and echocardiography for early diagnosis and intervention to mitigate mortality and morbidity risks associated with pericarditis and cardiac tamponade secondary to influenza B.

3.
J Med Chem ; 66(23): 16222-16234, 2023 12 14.
Artigo em Inglês | MEDLINE | ID: mdl-38051546

RESUMO

Duclauxin (1) from Talaromyces sp. IQ-313 was reported as a putative allosteric modulator of human recombinant protein tyrosine phosphatase 1B (400 amino acids) (hPTP1B1-400), a validated target for the treatment of type II diabetes. Based on these findings, a one-strain-many-compound (OSMAC) experiment on the IQ-313 strain generated derivatives 5a, 6, and 7. Moreover, a one-/two-step semisynthetic approach guided by docking toward hPTP1B1-400 produced 38 analogs, a series (A) incorporating a lactam functionalization at C-1 (8a-15a, 36a, and 37a) and a series (B) containing a lactam at C-1 and an extra unsaturation between C-7 and C-8 (5b, 11b-37b). In vitro evaluation and structure-activity relationship (SAR) analysis revealed that analogs from the B series are up to 10-fold more active than 1 and derivatives from the A series. Furthermore, duclauxin (1) and 36b were assessed for their potential acute toxicity, estimating their LD50 to be higher than 300 mg/kg. Moreover, 36b significantly reduced glycemia in an insulin tolerance test in mice, suggesting that its mechanism of action is through the PTP1B inhibition.


Assuntos
Diabetes Mellitus Tipo 2 , Camundongos , Humanos , Animais , Diabetes Mellitus Tipo 2/metabolismo , Relação Estrutura-Atividade , Lactamas , Inibidores Enzimáticos/farmacologia , Inibidores Enzimáticos/química , Simulação de Acoplamento Molecular , Proteína Tirosina Fosfatase não Receptora Tipo 1/metabolismo
4.
Eur Respir J ; 62(5)2023 11.
Artigo em Inglês | MEDLINE | ID: mdl-37945032

RESUMO

BACKGROUND: Observational studies suggest asthma is a risk factor for coronary heart disease (CHD) and sex modifies the risk, but they may suffer from methodological limitations. To overcome these, we applied a "triangulation approach", where different methodologies, with different potential biases, were leveraged to enhance confidence in findings. METHODS: First, we conducted an observational study using UK medical records to match asthma patients 1:1, by age, sex and general practitioner (GP) practice, to the general population. We measured the association between asthma and incident CHD (myocardial infarction: hospitalisation/death) by applying minimal sufficient adjustment: model 1, smoking, body mass index, oral corticosteroids, atopy and deprivation; model 2, additionally adjusting for healthcare behaviour (GP consultation frequency). Second, we conducted a Mendelian randomisation (MR) study using data from the UK Biobank, Trans-National Asthma Genetic Consortium (TAGC) and Coronary Artery Disease Genome-wide Replication and Meta-analysis consortium (CARDIoGRAM). Using 64 asthma single nucleotide polymorphisms, the effect of asthma on CHD was estimated with inverse variance-weighted meta-analysis and methods that adjust for pleiotropy. RESULTS: In our observational study (n=1 522 910), we found asthma was associated with 6% increased risk of CHD (model 1: HR 1.06, 95% CI 1.01-1.13); after accounting for healthcare behaviour, we found no association (model 2: HR 0.99, 95% CI 0.94-1.05). Asthma severity did not modify the association, but sex did (females: HR 1.11, 95% CI 1.01-1.21; males: HR 0.91, 95% CI 0.84-0.98). Our MR study (n=589 875) found no association between asthma and CHD (OR 1.01, 95% CI 0.98-1.04) and no modification by sex. CONCLUSIONS: Our findings suggest that asthma is not a risk factor for CHD. Previous studies may have suffered from detection bias or residual confounding.


Assuntos
Asma , Doença da Artéria Coronariana , Infarto do Miocárdio , Feminino , Humanos , Masculino , Análise de Variância , Asma/complicações , Asma/epidemiologia , Asma/genética , Estudo de Associação Genômica Ampla , Infarto do Miocárdio/epidemiologia , Polimorfismo de Nucleotídeo Único , Fatores de Risco , Análise da Randomização Mendeliana
5.
Cureus ; 15(11): e48919, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-38024047

RESUMO

Introduction and aim The surging incidence of type 2 diabetes has become a growing concern for the healthcare sector. This chronic ailment, characterized by its complex blend of genetic and lifestyle determinants, has witnessed a notable increase in recent times, exerting substantial pressure on healthcare resources. As more individuals turn to online platforms for health guidance and embrace the utilization of Chat Generative Pre-trained Transformer (ChatGPT; San Francisco, CA: OpenAI), a text-generating AI (TGAI), to get insights into their well-being, evaluating its effectiveness and reliability becomes crucial. This research primarily aimed to evaluate the correctness of TGAI responses to type 2 diabetes (T2DM) inquiries via ChatGPT. Furthermore, this study aimed to examine the consistency of TGAI in addressing common queries on T2DM complications for patient education. Material and methods Questions on T2DM were formulated by experienced physicians and screened by research personnel before querying ChatGPT. Each question was posed thrice, and the collected answers were summarized. Responses were then sorted into three distinct categories as follows: (a) appropriate, (b) inappropriate, and (c) unreliable by two seasoned physicians. In instances of differing opinions, a third physician was consulted to achieve consensus. Results From the initial set of 110 T2DM questions, 40 were dismissed by experts for relevance, resulting in a final count of 70. An overwhelming 98.5% of the AI's answers were judged as appropriate, thus underscoring its reliability over traditional online search engines. Nonetheless, a 1.5% rate of inappropriate responses underlines the importance of ongoing AI improvements and strict adherence to medical protocols. Conclusion TGAI provides medical information of high quality and reliability. This study underscores TGAI's impressive effectiveness in delivering reliable information about T2DM, with 98.5% of responses aligning with the standard of care. These results hold promise for integrating AI platforms as supplementary tools to enhance patient education and outcomes.

6.
Chem Biodivers ; : e202300829, 2023 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-37721179

RESUMO

Microbial mats are microbial communities capable of recycling the essential elements of life and considered to be the oldest evidence of microbial communities on Earth. Due to their uniqueness and limited sampling material, analyzing their metabolomic profile in different seasons or conditions is challenging. In this study, microbial mats from a small pond in the Cuatro Cienegas Basin in Coahuila, Mexico, were collected in wet and dry seasons. In addition to these samples, mesocosm experiments from the wet samples were set. These mats are elastic and rise after heavy rainfall by forming gas domes structures known as "Archean domes", by the outgassing of methanogenic bacteria, archaea, and sulfur bacteria. Extracts from all mats and mesocosms were subjected to untargeted mass spectrometry-based metabolomics and molecular networking analysis. Interestingly, each mat showed high chemical diversity that may be explained by the temporal dynamic processes in which they were sampled.

7.
EClinicalMedicine ; 61: 102056, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-37425375

RESUMO

Background: Although there is growing evidence that former professional athletes from sports characterised by repetitive head impact subsequently experience an elevated risk of dementia, the occurrence of this disorder in retired amateurs, who represent a larger population, is uncertain. The present meta-analysis integrates new results from individual-participant analyses of a cohort study of former amateur contact sports participants into a systematic review of existing studies of retired professionals and amateurs. Methods: The cohort study comprised 2005 male retired amateur athletes who had competed internationally for Finland (1920-1965) and a general population comparison group of 1386 age-equivalent men. Dementia occurrence was ascertained from linked national mortality and hospital records. For the PROSPERO-registered (CRD42022352780) systematic review, we searched PubMed and Embase from their inception to April 2023, including cohort studies published in English that reported standard estimates of association and variance. Study-specific estimates were aggregated using random-effect meta-analysis. An adapted Cochrane Risk of Bias Tool was used to assess study quality. Findings: In the cohort study, up to 46 years of health surveillance of 3391 men gave rise to 406 dementia cases (265 Alzheimer's disease). After adjustment for covariates, former boxers experienced elevated rates of dementia (hazard ratio: 3.60 [95% CI 2.46, 5.28]) and Alzheimer's disease (4.10 [2.55, 6.61]) relative to general population controls. Associations were of lower magnitude in retired wrestlers (dementia: 1.51 [0.98, 2.34]; Alzheimer's disease: 2.11 [1.28, 3.48]) and soccer players (dementia: 1.55 [1.00, 2.41]; Alzheimer's disease: 2.07 [1.23, 3.46]), with some estimates including unity. The systematic review identified 827 potentially eligible published articles, of which 9 met our inclusion criteria. These few retrieved studies all sampled men and the majority were of moderate quality. In sport-specific analyses according to playing level, there was a marked difference in dementia rates in onetime professional American football players (2 studies; summary risk ratio: 2.96 [95% CI 1.66, 5.30]) relative to amateurs in whom there was no suggestion of an association (2 studies; 0.90 [0.52, 1.56]). For soccer players, while dementia occurrence was raised in both erstwhile professionals (2 studies; 3.61 [2.92, 4.45]) and amateurs (1 study; 1.60 [1.11, 2.30]) there was again a suggestion of a risk differential. The only studies of boxers comprised former amateurs in whom there was a tripling in the rates of dementia (2 studies; 3.14 [95% CI 1.72, 5.74]) and Alzheimer's disease (2 studies; 3.07 [1.01, 9.38]) at follow-up compared to controls. Interpretation: Based on a small number of studies exclusively sampling men, former amateur participants in soccer, boxing, and wrestling appeared to experience an elevated risk of dementia relative to the general population. Where data allowed comparison, there was a suggestion that risks were greater amongst retired professionals relative to amateurs in the sports of soccer and American football. Whether these findings are generalisable to the contact sports not featured, and to women, warrants examination. Funding: This work was unfunded.

8.
BMC Med ; 21(1): 216, 2023 06 19.
Artigo em Inglês | MEDLINE | ID: mdl-37337233

RESUMO

BACKGROUND: High-sensitivity cardiac troponin testing is a promising tool for cardiovascular risk prediction, but whether serial testing can dynamically predict risk is uncertain. We evaluated the trajectory of cardiac troponin I in the years prior to a cardiovascular event in the general population, and determine whether serial measurements could track risk within individuals. METHODS: In the Whitehall II cohort, high-sensitivity cardiac troponin I concentrations were measured on three occasions over a 15-year period. Time trajectories of troponin were constructed in those who died from cardiovascular disease compared to those who survived or died from other causes during follow up and these were externally validated in the HUNT Study. A joint model that adjusts for cardiovascular risk factors was used to estimate risk of cardiovascular death using serial troponin measurements. RESULTS: In 7,293 individuals (mean 58 ± 7 years, 29.4% women) cardiovascular and non-cardiovascular death occurred in 281 (3.9%) and 914 (12.5%) individuals (median follow-up 21.4 years), respectively. Troponin concentrations increased in those dying from cardiovascular disease with a steeper trajectory compared to those surviving or dying from other causes in Whitehall and HUNT (Pinteraction < 0.05 for both). The joint model demonstrated an independent association between temporal evolution of troponin and risk of cardiovascular death (HR per doubling, 1.45, 95% CI,1.33-1.75). CONCLUSIONS: Cardiac troponin I concentrations increased in those dying from cardiovascular disease compared to those surviving or dying from other causes over the preceding decades. Serial cardiac troponin testing in the general population has potential to track future cardiovascular risk.


Assuntos
Doenças Cardiovasculares , Humanos , Feminino , Masculino , Estudos Longitudinais , Doenças Cardiovasculares/diagnóstico , Troponina I , Biomarcadores , Estudos de Coortes , Fatores de Risco
9.
Anal Biochem ; 674: 115195, 2023 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-37268197

RESUMO

In this work, a quantitative sandwich ELISA was optimized, through a full factorial design of experiments (DOE) in successive steps of a preliminary protocol obtained by the method of one factor at a time (OFAT). The specificity of the optimized ELISA, the lower limit of quantification, the quantification range and the analytical sensitivity of the antigen quantification curve were evaluated, in comparison with the curve obtained from the preliminary protocol. The full factorial DOE was linked to a simple statistical processing, which facilitates the interpretation of the results in those laboratories where there is no trained statistician. The step-by-step optimization of the ELISA and the successive incorporation into the protocol of the best combination of factors and levels, allowed obtaining a specific immunoassay, with an analytical sensitivity 20 times greater and with a lower limit of antigen quantification that decreased from 156.25 at 9.766 ng/mL. As far as we know, there are no reports of optimization of an ELISA following the step-by-step scheme used in this work. The optimized ELISA will be used for the quantification of the TT-P0 protein, the active principle of a vaccine candidate against sea lice.


Assuntos
Antígenos , Ensaio de Imunoadsorção Enzimática/métodos , Imunoensaio
10.
Artigo em Espanhol | LILACS-Express | LILACS | ID: biblio-1535139

RESUMO

Introducción: La equinococosis esplénica es una enfermedad zoonótica adquirida de forma accidental por el humano como huésped intermediario. Reporte de caso: paciente mujer de 26 años de edad, con dolor abdominal localizado en hipocondrio izquierdo, moderada intensidad, calmaba con antiespasmódicos endovenosos; antecedente de dolor abdominal de larga data y procedente de región de Huancavelica, Perú hace 6 años. En examen clínico del abdomen: ruidos hidroaéreos; presentes, simétrico, blando, depresible, doloroso a la palpación en hipocondrio izquierdo, impresiona esplenomegalia, timpanismo conservado; en ecografía menciona quiste hidatídico a nivel del bazo Gharbi IV; en tomografía abdominopélvica con contraste muestra bazo con lesión quística heterogénea, de pared parcialmente calcificada y áreas de densidad grasa que se extiende hasta ligamento gastroesplénico, con diámetro de 73 mm x 54 mm; concluyendo equinococosis extrahepática (equinococosis esplénica), realizándose esplenectomía total. Conclusión: enfermedad rara, incluso en áreas endémicas, que plantea desafíos para su diagnóstico y tratamiento.


SUMMARY Introduction: Splenic echinococcosis is a zoonotic disease accidentally acquired by humans as an intermediate host. Case report: a 26-year-old female patient with abdominal pain located in the left hypochondrium, moderate intensity, calmed with intravenous antispasmodics; a history of long-standing abdominal pain and from the Huancavelica region, Peru, 6 years ago. On clinical examination of the abdomen: hydro-air sounds; present, symmetrical, soft, depressible, painful on palpation in the left hypochondrium, impression of splenomegaly, preserved tympany; the ultrasound mentions a hydatid cyst at the level of the spleen Gharbi IV; Contrast-enhanced abdominal and pelvic tomography shows a spleen with a heterogeneous cystic lesion, with a partially calcified wall and areas of fatty density that extend to the gastrosplenic ligament, with a diameter of 73 mm x 54 mm; concluding extrahepatic echinococcosis (splenic echinococcosis), performing total splenectomy. Conclusion: rare disease, even in endemic areas, which poses challenges for its diagnosis and treatment.

11.
Physiol Plant ; 174(6): e13836, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36453084

RESUMO

The bean fruit pericarp accumulates a significant amount of starch, which starts to be degraded 20 days after anthesis (DAA) when seed growth becomes exponential. This period is also characterized by the progressive senescence of the fruit pericarp. However, the chloroplasts maintained their integrity, indicating that starch degradation is a compartmentalized process. The process coincided with a transient increase in maltose and sucrose levels, suggesting that ß-amylase is responsible for starch degradation. Starch degradation in the bean fruit pericarp is also characterized by a large increase in starch phosphorylation, as well as in the activities of cytosolic disproportionating enzyme 2 (DPE2, EC 2.4.1.25) and glucan phosphorylase (PHO2, EC 2.4.1.1). This suggests that the rate of starch degradation in the bean fruit pericarp 20 DAA is dependent on the transformation of starch to a better substrate for ß-amylase and the increase in the rate of cytosolic metabolism of maltose.


Assuntos
Arabidopsis , beta-Amilase , Maltose/metabolismo , Frutas/metabolismo , beta-Amilase/metabolismo , Arabidopsis/metabolismo , Amido/metabolismo
12.
Asian Pac J Cancer Prev ; 23(11): 3623-3628, 2022 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-36444573

RESUMO

OBJECTIVE: We estimated the mortality trends for prostate cancer in Peru and its geographical areas between 2003 and 2017. MATERIAL AND METHODS: We obtained recorded prostate cancer deaths from the Peruvian Ministry of Health Database between 2003 and 2017. Age-adjusted mortality rates per 100,000 men-year were computed with the direct method using the world standard SEGI population. We estimated the annual percent change (APC) using the Joinpoint regression program. RESULTS: A total of 38,617 prostate cancer deaths were reported between 2003 and 2017, with a mortality rate ranging from 18.21 to 19.94 deaths per 100,000 men-year. Since 2006, Peru has experienced a decrease of 2.2 deaths per year, whereas the mortality rate in the coastal region has declined by 2.9% per year.  The highlands and rainforest regions showed stable trends throughout the entire study period. According to provinces, only Moquegua had a significant decrease (APC: -6.0, 95%CI: -11.4, -0.2, p<0.05) from 2003 to 2017. CONCLUSIONS: Although mortality rates are decreasing, there is a high mortality burden by prostate cancer in Peru and by geographical regions, being mostly concentrated in the coastal region. The rainforest provinces deserve the most attention. Our findings suggest wide health care disparities among the different regions of Peru that need greater public health attention to reduce the burden of mortality by prostate cancer.


Assuntos
Próstata , Neoplasias da Próstata , Masculino , Humanos , Peru/epidemiologia , Neoplasias da Próstata/epidemiologia , Pelve , Bases de Dados Factuais
13.
Artigo em Espanhol | LILACS-Express | LILACS | ID: biblio-1431306

RESUMO

Introducción: Los aneurismas intracerebrales son hallazgos incidentales en estudios de imágenes realizado por otros diagnósticos. Reporte de Caso: Paciente femenino de 35 años, que presentó sincope después de cefalea de gran intensidad sin ceder a tratamiento convencional de AINES; con antecedente de cefalea de larga data y tratamiento esporádico. Al examen: neurológico: despierta, asimetría facial, disartria, fuerza muscular disminuida en ambos miembros inferiores, no signos meníngeos; el informe tomográfico cerebral sin contraste indicó: lesiones cerebrales expansivas de etiología a determinar a nivel de ambos lados de diencéfalo: descartar glioma vs aneurismas; Angiotac cerebral con contraste, refleja aneurismas de carótida interna intracraneal bilateral y cerebral media (en espejo). Posteriormente la paciente fue evaluada por neurocirujano de turno, quien indica referir a centro de mayor complejidad, por no contar con instrumental necesario para intervención quirúrgica; paciente fallece camino a centro de referencia. Conclusiones: Al ser una patología poco frecuente, no es considerada como una primera opción de sospecha diagnostica tras un evento de cefalea.


Background: Intracerebral aneurysms are incidental findings in imaging studies performed for other diagnoses. Case Report: 35- year-old female patient, who presented syncope after severe headache without yielding to conventional treatment with NSAIDs; with a history of long-standing headache and sporadic treatment. On examination: neurological: awake, facial asymmetry, dysarthria, decreased muscle strength in both lower limbs, no meningeal signs; the brain tomographic report without contrast indicated: expansive brain lesions of etiology to be determined at both sides of the diencephalon: rule out glioma vs aneurysms; cerebral Angiotac with contrast, reflects bilateral intracranial internal carotid and middle cerebral (mirror) aneurysms. Subsequently the patient was evaluated by the neurosurgeon on duty, who indicated to refer to a center of higher complexity, for not having the necessary instruments for surgery; patient died on the way to the referral center. Conclusions: Being a rare pathology, it is not considered as a first option for diagnostic suspicion after a headache event.

14.
ACS Omega ; 7(14): 12171-12185, 2022 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-35449929

RESUMO

Cenotes are habitats with unique physical, chemical, and biological features. Unexplored microorganisms from these sinkholes represent a potential source of bioactive molecules. Thus, a series of cultivable fungi (Aspergillus spp. NCA257, NCA264, and NCA276, Stachybotrys sp. NCA252, and Cladosporium sp. NCA273) isolated from the cenote Tza Itzá were subjected to chemical, coculture, and metabolomic analyses. Nineteen compounds were obtained and tested for their antimicrobial potential against ESKAPE pathogens, Mycobacterium tuberculosis, and nontuberculous mycobacteria. In particular, phenylspirodrimanes from Stachybotrys sp. NCA252 showed significant activity against MRSA, MSSA, and mycobacterial strains. On the other hand, the absolute configuration of the new compound 17-deoxy-aspergillin PZ (1) isolated from Aspergillus sp. NCA276 was established via single-crystal X-ray crystallography. Also, the chemical analysis of the cocultures between Aspergillus and Cladosporium strains revealed the production of metabolites that were not present or were barely detected in the monocultures. Finally, molecular networking analysis of the LC-MS-MS/MS data for each fungus was used as a tool for the annotation of additional compounds, increasing the chemical knowledge on the corresponding fungal strains. Overall, this is the first systematic chemical study on fungi isolated from a sinkhole in Mexico.

15.
Planta Med ; 88(9-10): 729-734, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35354220

RESUMO

Chemical investigation of Punctularia atropurpurascens strain HM1 (Punctulariaceae), a corticioid isolated from a decorticated piece of Quercus bark collected in Bosque de Tlalpan, Mexico City, led to the isolation of a new drimane, 1-α-hydroxy-isodrimenine (1: ) and a new tetrahydroxy kauranol, 16-hydroxy-phlebia-nor-kauranol (2: ), together with the known N-phenylacetamide (3: ). Structures of all compounds were elucidated by spectroscopic and spectrometric methods, and the absolute configuration of 1: and 2: was confirmed via single-crystal X-ray crystallography. The isolated compounds showed modest antimycobacterial activity.


Assuntos
Basidiomycota , Terpenos , Antibacterianos/farmacologia , Cristalografia por Raios X , Fungos , Estrutura Molecular , Terpenos/farmacologia
16.
Hypertension ; 79(4): 836-843, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-35139665

RESUMO

BACKGROUND: Aortic pulse wave velocity is a noninvasive measure of aortic stiffness and arterial aging. Its current value in cardiovascular risk estimation practice is unknown. We aimed to establish whether aortic pulse wave velocity identified individuals with higher risk of incident major adverse cardiovascular events and improved performance of the American Heart Association/American College of Cardiology atherosclerotic cardiovascular disease risk score. METHODS: This prospective analysis included 3837 Whitehall II cohort participants screened in 2008 to 2009, and followed for 11.7 years (mean=10.3, SD=1.81), without history of stroke, myocardial infarction, or coronary heart disease. RESULTS: Mean age of the sample was 65.0 years (SD=5.6), 2831 participants (73.8%) were male and mean atherosclerotic cardiovascular disease risk score was 13.8%. At the end of follow-up, 411 individuals (10.7%) had suffered a major cardiovascular event. Those in the highest aortic pulse wave velocity quartile were at high risk (hazard ratio, 2.99 [95% CI, 2.25-3.97]) and reached the threshold for statin medication (7.5% risk) after 5 years whereas others reached it after 10 years (difference P<0.001). The addition of aortic pulse wave velocity to the risk score improved the C statistic (0.68 versus 0.67, P=0.03) and net reclassification index (4.6%, P=0.04 and 11.3%, P=0.02). CONCLUSIONS: Our results show that aortic stiffness predicted major adverse cardiovascular events in a cohort of elderly individuals, improving the performance of a widely used cardiovascular disease risk estimator. Aortic pulse wave velocity measurement is scalable, radiation-free, and easy to perform. Further studies on its applicability in cardiovascular disease risk assessment in primary care settings are needed.


Assuntos
Doenças Cardiovasculares , Rigidez Vascular , Idoso , Aorta , Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/epidemiologia , Feminino , Humanos , Masculino , Estudos Prospectivos , Análise de Onda de Pulso , Fatores de Risco
17.
J Immunol Methods ; 500: 113195, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34843713

RESUMO

COVID-19 pandemic poses a serious threat to human health; it has completely disrupted global stability, making vaccine development an important goal to achieve. Monoclonal antibodies play an important role in subunit vaccines strategies. In this work, nine murine MAbs against the RBD of the SARS-CoV-2 spike protein were obtained by hybridoma technology. Characterization of purified antibodies demonstrated that five of them have affinities in the order of 108 L/mol. Six MAbs showed specific recognition of different recombinant RBD-S antigens in solution. Studies of the additivity index of anti-RBD antibodies, by using a novel procedure to determine the additivity cut point, showed recognition of at least five different epitopes. The MAbs CBSSRBD-S.11 and CBSSRBD-S.8 revealed significant neutralizing capacity against SARS-CoV-2 in an ACE2-RBD binding inhibition assay (IC50 = 85.5pM and IC50 = 122.7pM, respectively) and in a virus neutralizing test with intact SARS-CoV-2 (VN50 = 0.552 nM and VN50 = 4.854 nM, respectively) when D614G strain was used to infect Vero cells. Also CBSSRBD-S.11 neutralized the SARS-CoV-2 strains Alpha and Beta: VN50 = 0.707 nM and VN50 = 0.132 nM, respectively. The high affinity CBSSRBD-S.8 and CBSSRBD-S.7 recognized different epitopes, so they are suitable for the development of a sandwich ELISA to quantitate RBD-S recombinant antigens in biomanufacturing processes, as well as in pharmacokinetic studies in clinical and preclinical trials.


Assuntos
Anticorpos Monoclonais/metabolismo , Vacinas contra COVID-19/imunologia , COVID-19/diagnóstico , SARS-CoV-2/fisiologia , Enzima de Conversão de Angiotensina 2/metabolismo , Animais , Anticorpos Monoclonais/genética , COVID-19/imunologia , Vacinas contra COVID-19/genética , Ensaios Clínicos como Assunto , Feminino , Engenharia Genética , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Domínios e Motivos de Interação entre Proteínas/genética , Desenvolvimento de Vacinas , Vacinas de Subunidades Antigênicas/genética
18.
Lancet Reg Health Am ; 16: 100376, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36777153

RESUMO

Background: An up-to-date analysis of gastric cancer mortality among Hispanic/Latino populations is required for estimating disease burden and assessing the effectiveness of clinical and preventive strategies. Methods: We retrieved gastric cancer deaths between 1997 and 2017 (as available) from the Surveillance, Epidemiology, and End Results Program (United States Hispanics) and the World Health Organization databases (Puerto Rico, 16 Latin American and Caribbean countries). Joinpoint regression analysis was used to examine trends in age-standardized mortality rates (ASMR; per 100 000 person-years) and calculate average annual percent changes (AAPCs) by country (or territory), age group (25-49 and ≥50 years), and sex. Trends were compared to assess slope parallelism. Findings: In 2017, Chile (31·8), Colombia (24·3) and Costa Rica (24·3) had the highest ASMR of gastric cancer for men, while Guatemala (17·2), Peru (13·5), and Costa Rica (13·3) had the highest ASMR for women. Small-to-moderate mortality declines (AAPCs ranged -4 to -0.5%) were observed between 1997 and 2017. In almost all countries, trends decreased among individuals aged ≥50 years. However, age-specific trends were not parallel (p-values <0.05) in Brazil, Colombia, Mexico, the United States, and Venezuela for both men and women, and in five additional countries for only women; with a few countries showing stable or slightly increasing trends for individuals aged 25-49 years. Interpretation: Overall gastric cancer mortality rates in Hispanics/Latinos declined in the last two decades. However, there was a notable variation in trends by country, sex, and age group. Continued and targeted prevention efforts are needed to reduce the disease burden in these vulnerable populations. Funding: Universidad Cientifica del Sur, Peru, and National Cancer Institute, United States.

19.
Molecules ; 26(23)2021 Dec 02.
Artigo em Inglês | MEDLINE | ID: mdl-34885908

RESUMO

A collection of 29 cultivable fungal strains isolated from deep-sea sediments of the Gulf of Mexico were cultivated under the "one strain, many compounds" approach to explore their chemical diversity and antimicrobial potential. From the 87 extracts tested, over 50% showed antimicrobial activity, and the most active ones were those from cultures grown at 4 °C in darkness for 60 days (resembling deep-sea temperature). PCA analysis of the LC-MS data of all the extracts confirmed that culture temperature is the primary factor in the variation of the 4462 metabolite features, accounting for 21.3% of the variation. The bioactivity-guided and conventional chemical studies of selected fungal strains allowed the identification of several active and specialized metabolites. Finally, metabolomics analysis by GNPS molecular networking and manual dereplication revealed the biosynthetic potential of these species to produce interesting chemistry. This work uncovers the chemical and biological study of marine-derived fungal strains from deep-sea sediments of the Gulf of Mexico.


Assuntos
Anti-Infecciosos/química , Fungos/química , Anti-Infecciosos/metabolismo , Anti-Infecciosos/farmacologia , Produtos Biológicos/química , Produtos Biológicos/metabolismo , Produtos Biológicos/farmacologia , Fungos/metabolismo , Sedimentos Geológicos/microbiologia , Golfo do México , Metaboloma
20.
Am J Cancer Res ; 11(9): 4127-4140, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34659880

RESUMO

Drug resistance is one of the main causes of chemotherapy failure. Although several factors are involved in cancer drug resistant, the exporter pumps overexpression that mediates the drugs flow to outside the cells and reduces both the drugs intracellular concentration and effectiveness, has been one of the most important challenges. Overexpression of ABCC3, a member of the ABCC subfamily, has been strongly associated to the resistance to multiple drugs. ABCC3 has been found highly expressed in different types of cancers and is associated with poor prognosis and resistance to treatments. In this review, we summarize the molecular mechanisms involved in cancer drug resistance and discuss the current knowledge about the structure, function and role of ABCC3 in drug resistance, as well as, the expression status of ABCC3 in different types of cancer. We also provide evidences that place ABCC3 as a potential therapeutic target for improving the cancer treatment by focusing on the need of developing more effective cancer therapies to target ABCC3 in translational researches.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...