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1.
Biochem Genet ; 62(1): 352-370, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37347449

RESUMO

Malignant pleural mesothelioma (MPM) is a rare and aggressive neoplasm of the pleural tissue that lines the lungs and is mainly associated with long latency from asbestos exposure. This tumor has no effective therapeutic opportunities nowadays and has a very low five-year survival rate. In this sense, identifying molecular events that trigger the development and progression of this tumor is highly important to establish new and potentially effective treatments. We conducted a meta-analysis of genome-wide expression studies publicly available at the Gene Expression Omnibus (GEO) and ArrayExpress databases. The differentially expressed genes (DEGs) were identified, and we performed functional enrichment analysis and protein-protein interaction networks (PPINs) to gain insight into the biological mechanisms underlying these genes. Additionally, we constructed survival prediction models for selected DEGs and predicted the minimum drug inhibition concentration of anticancer drugs for MPM. In total, 115 MPM tumor transcriptomes and 26 pleural tissue controls were analyzed. We identified 1046 upregulated DEGs in the MPM samples. Cellular signaling categories in tumor samples were associated with the TNF, PI3K-Akt, and AMPK pathways. The inflammatory response, regulation of cell migration, and regulation of angiogenesis were overrepresented biological processes. Expression of SOX17 and TACC1 were associated with reduced survival rates. This meta-analysis identified a list of DEGs in MPM tumors, cancer-related signaling pathways, and biological processes that were overrepresented in MPM samples. Some therapeutic targets to treat MPM are suggested, and the prognostic potential of key genes is shown.


Assuntos
Neoplasias Pulmonares , Mesotelioma Maligno , Mesotelioma , Neoplasias Pleurais , Humanos , Mesotelioma/genética , Mesotelioma/metabolismo , Fosfatidilinositol 3-Quinases , Neoplasias Pleurais/genética , Neoplasias Pleurais/metabolismo , Neoplasias Pulmonares/patologia
2.
J Sci Food Agric ; 104(3): 1367-1381, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37776152

RESUMO

BACKGROUND: Cocoa quality plays a pivotal role in establishing denominations of origin, with genotypes, geography, climate and soil conditions being key variables. However, these factors have not been comprehensively explored in defining cacao denominations of origin. The present study addresses this gap by laying the foundation for cacao denomination of origin, focusing on the Buenaventura region on Colombia's Pacific coast. Our goal is to provide a holistic understanding of the elements underpinning cacao denomination of origin, emphasizing Buenaventura's unique cocoa quality and geographical significance. RESULTS: Through the Buenaventura case, we propose a robust framework applicable to other cacao-producing regions, elevating the recognition and value of cacao denomination of origin. Our framework encompasses geography, agronomy, genetics, microbial diversity, pests and diseases and cocoa quality. In a pioneering move, we propose a cacao denomination of origin in Colombia, specifically examining Bajo Calima, Sabaletas and Cisneros within Buenaventura region. Buenaventura stands out for its cocoa quality, characterized by fruity flavors attributed to the rich biodiversity of the lowland rainforest. CONCLUSION: Our analysis indicates specific geographical indicators for each of the study zones, with Buenaventura identified as a region with natural characteristics to produce fine flavour cocoa products. Each zone exhibited a high differentiation and diversity of cacao cultivars. Buenaventura has the potential to be designated as a future denomination of origin for cacao from the Pacific region of Colombia, characterized by its unique fruity-aroma chocolates. Our framework is adaptable to other cacao-producing regions, facilitating the establishment of denominations of origin within the cocoa industry and agriculture. © 2023 The Authors. Journal of The Science of Food and Agriculture published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.


Assuntos
Cacau , Chocolate , Colômbia , Agricultura , Frutas
3.
Environ Monit Assess ; 196(4): 387, 2024 Mar 21.
Artigo em Inglês | MEDLINE | ID: mdl-38509267

RESUMO

The district of Arauca is the second-largest producer of cacao in Colombia. However, despite its quality, it faces issues for export due to levels of cadmium (Cd) higher than the regulatory thresholds. A central question is how it may impact agricultural performance in the presence of Cd in cacao and chocolates. This study quantified Cd in cacao plantations from Arauca. Thus, 180 farms were assessed in the municipalities of Arauquita, Fortul, Saravena, and Tame. Five sample types (soil, irrigation channel sediment, soil litter, cacao seeds, and chocolates) were assessed for Cd. As a technological innovation, the new MXRF technology was used for Cd in chocolates. The sequence of Cd content was soil litter > chocolate > soils > cacao seeds > irrigation-channel sediment. A gradient north-south of Cd content in soil was observed, where highest content was found in farms near the Arauca River, and lower farther away. In irrigation channel sediment, Cd levels averaged 0.07 mg kg-1. The Cd content in cacao seeds was 0.78 mg kg-1 on average. Cd content in chocolates was above the threshold (1.10 mg kg-1 on average, including several cacao mass percentages). These artisanal chocolate bars produced by single farms were near the limit of Cd set by the European Union (up to 0.8 mg kg-1). Therefore, mixing beans from different farms could reduce their Cd content. The present study underscores the complexity of Cd distribution, emphasizing the importance of integrating soil, crop, and landscape features in managing and mitigating Cd levels in cacao.


Assuntos
Cacau , Poluentes do Solo , Cádmio/análise , Colômbia , Monitoramento Ambiental , Poluentes do Solo/análise , Solo , Produtos Agrícolas
4.
Phys Chem Chem Phys ; 24(27): 16556-16565, 2022 Jul 13.
Artigo em Inglês | MEDLINE | ID: mdl-35770743

RESUMO

Transition metal carbides are increasingly used as catalysts for the transformation of CO2 into useful chemicals. Recently, the effect of nanostructuring of such carbides has started to gain relevance in tailoring their catalytic capabilities. Catalytic materials based on molybdenum carbide nanoparticles (MoCy) have shown a remarkable ability to bind CO2 at room temperature and to hydrogenate it into oxygenates or light alkanes. However, the involved chemistry is largely unknown. In the present work, a systematic computational study is presented aiming to elucidate the chemistry behind the bonding of CO2 with a representative set of MoCy nanoparticles of increasing size, including stoichiometric and non-stoichiometric cases. The obtained results provide clear trends to tune the catalytic activity of these systems and to move towards more efficient CO2 transformation processes.

5.
Phys Chem Chem Phys ; 23(36): 20255-20267, 2021 Sep 22.
Artigo em Inglês | MEDLINE | ID: mdl-34477186

RESUMO

Hydrogenation reactions are involved in several processes in heterogeneous catalysis. Platinum is the best-known catalyst; however, there are limitations to its practical use. Therefore, it is necessary to explore alternative materials and transition metal carbides (TMCs) have emerged as potential candidates. We explore the possibility of using cheap TMCs as supports for a Pt monolayer, aiming to reduce the amount of the noble metal in the catalyst without a significant loss of its activity towards H2 dissociation. Hence, analyzing H2 dissociation from a fundamental point of view is a necessary step towards a further practical catalyst. By means of periodic DFT calculations, we analyze H2 adsorption and dissociation on Pt/ß-Mo2C and Pt/α-WC surfaces, as a function of hydrogen surface coverage (ΘH), resembling a more realistic model of a catalyst. H2 dissociation rates were analyzed as a function of the reaction temperature. The results show that Pt/C-WC and Pt/Mo-Mo2C have a Pt-like behavior for H2 dissociation at ΘH > 1/2 ML. At a particular temperature of 298 K, Pt/C-WC and Pt/Mo-Mo2C have low energy barriers for H2* → 2H* (0.13 and 0.11 eV, respectively), close to the value of Pt (0.06 eV). For the highest coverage, i.e. ΘH = 1, Pt/C-WC has a lower activation energy and a higher reaction rate than Pt. Finally, the H2 dissociation rate is higher in Pt/Mo-Mo2C than in Pt when increasing the temperature above 298 K. Our results put Pt/C-WC and Pt/Mo-Mo2C under the spotlight as potential catalysts for H2 dissociation, with a similar performance to Pt, paving the way for further experimental and/or theoretical studies, addressing the capability of Pt/TMC as practical catalysts in hydrogenation reactions.

6.
Proc Natl Acad Sci U S A ; 115(16): E3769-E3778, 2018 04 17.
Artigo em Inglês | MEDLINE | ID: mdl-29615514

RESUMO

Pancreatic ductal adenocarcinoma (PDA) remains one of the most lethal tumor types, with extremely low survival rates due to late diagnosis and resistance to standard therapies. A more comprehensive understanding of the complexity of PDA pathobiology, and especially of the role of the tumor microenvironment in disease progression, should pave the way for therapies to improve patient response rates. In this study, we identify galectin-1 (Gal1), a glycan-binding protein that is highly overexpressed in PDA stroma, as a major driver of pancreatic cancer progression. Genetic deletion of Gal1 in a Kras-driven mouse model of PDA (Ela-KrasG12Vp53-/- ) results in a significant increase in survival through mechanisms involving decreased stroma activation, attenuated vascularization, and enhanced T cell infiltration leading to diminished metastasis rates. In a human setting, human pancreatic stellate cells (HPSCs) promote cancer proliferation, migration, and invasion via Gal1-driven pathways. Moreover, in vivo orthotopic coinjection of pancreatic tumor cells with Gal1-depleted HPSCs leads to impaired tumor formation and metastasis in mice. Gene-expression analyses of pancreatic tumor cells exposed to Gal1 reveal modulation of multiple regulatory pathways involved in tumor progression. Thus, Gal1 hierarchically regulates different events implicated in PDA biology including tumor cell proliferation, invasion, angiogenesis, inflammation, and metastasis, highlighting the broad therapeutic potential of Gal1-specific inhibitors, either alone or in combination with other therapeutic modalities.


Assuntos
Carcinoma Ductal Pancreático/terapia , Galectina 1/fisiologia , Galectinas/fisiologia , Terapia de Alvo Molecular , Neoplasias Pancreáticas/terapia , Animais , Carcinoma Ductal Pancreático/irrigação sanguínea , Carcinoma Ductal Pancreático/genética , Carcinoma Ductal Pancreático/imunologia , Divisão Celular/genética , Movimento Celular/genética , Meios de Cultivo Condicionados , Galectinas/genética , Regulação Neoplásica da Expressão Gênica , Técnicas de Silenciamento de Genes , Ontologia Genética , Xenoenxertos , Humanos , Linfócitos do Interstício Tumoral/imunologia , Camundongos , Camundongos Knockout , Camundongos Transgênicos , Metástase Neoplásica , Neovascularização Patológica , Neoplasias Pancreáticas/irrigação sanguínea , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/imunologia , Células Estreladas do Pâncreas/metabolismo , Células Estreladas do Pâncreas/transplante , Comunicação Parácrina , RNA Interferente Pequeno/genética , Células Estromais/metabolismo , Microambiente Tumoral
7.
Phys Chem Chem Phys ; 21(31): 17332-17342, 2019 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-31355380

RESUMO

Density functional calculations were used to evaluate the ability of cubic and hexagonal phases of tungsten carbide to bind ethylene, as a model compound of unsaturated hydrocarbons, since its adsorption is the first step in important catalytic processes. The calculations give the following trend in stability: α-WC(0001)-C > α-WC(0001)-W > Pt(111) > γ-WC(001), with the binding energy varying in the range of -0.72 to -2.91 eV. The sub-surface layers play a crucial role in the binding, favoring a charge reorganization at extended ranges (above 6 Å) from bulk towards the surface, however, the electronic structure of the surface was modified only in the topmost layer. The surface sites for geometric C2H4 activation were identified, leading to a surface distortion due to an upwards shifting of surface atoms in the range 0.13-0.61 Å observed in Pt(111), α-WC(0001)-C, and γ-WC(001), with distortion energies of 0.13, 0.15 and 0.61 eV, respectively. The activation of C2H4 on tungsten carbides was compared with other transition metal carbide surfaces, which leads to a general classification of the elongation of carbon-carbon bond into a set of only three groups. If the interest is to activate ethylene C[double bond, length as m-dash]C bond, the surface sites and the binding modes should be those of the groups II and III. The infrared spectra show mainly four useful signals as a fingerprint to support and complement future experiments. The results of this work indicate that the α-WC-W surface could be directly responsible for the catalytic performance, while the binding of olefins on α-WC-C could cause surface poisoning. The metastable γ-WC(001) surface could be a promising system as compared to the known α-WC(0001) surface, but challenges arise regarding its synthesis, stability and catalytic performance. These results pave the way to address further experimental and theoretical studies focused on the hydrogenation of ethylene and more complex unsaturated hydrocarbons.

8.
Eur Arch Otorhinolaryngol ; 276(2): 357-365, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30535977

RESUMO

PURPOSE: To present a modified method of local infiltration (MMLI) for endoscopic stapes surgery to reduce surgical time, bleeding and complications. MATERIALS AND METHODS: This study involved 70 patients who underwent stapes surgery for otosclerosis by endoscopic and microscopic approaches. The MMLI was applied as follows: local infiltration was performed with one hand while the other hand inserted the endoscope into the ear canal to observe vasoconstriction signs on the monitor; the single site of infiltration was located at the center of the anterior conchal cartilage. Operative time, intraoperative blood loss, preservation of anatomical structures, postoperative hearing and complications were evaluated. RESULTS: The MMLI allowed for quick bleeding control and a clear and dry operative field. Operative time, intraoperative blood loss and preservation of anatomical structures were significantly reduced in the endoscopic group (P < 0.00) versus the microscopic group. The scutum was removed less frequent in the endoscopic group 7.1% versus 53.6% of the microscopic group (P < 0.00). The chorda tympani was preserved in all cases but it was more manipulated in the microscopic group 39.3% versus 9.5% of the endoscopic group (P < 0.00). No complications were observed and the hearing outcomes were significantly better than the preoperative thresholds. CONCLUSIONS: This is the first report on the use of a MMLI for endoscopic stapes surgery. Using this method, the surgeon performs the infiltration at one site and concurrently observes the vasoconstriction signs without the use of a microscope, frontal lamp or speculum. This method provides benefits in terms of operative time and complications.


Assuntos
Anestésicos Locais/administração & dosagem , Endoscopia/métodos , Cirurgia do Estribo/métodos , Adolescente , Adulto , Perda Sanguínea Cirúrgica , Endoscópios , Epinefrina/administração & dosagem , Feminino , Humanos , Lidocaína/administração & dosagem , Masculino , Microscopia , Pessoa de Meia-Idade , Duração da Cirurgia , Otosclerose/cirurgia , Projetos Piloto , Complicações Pós-Operatórias , Método Simples-Cego , Adulto Jovem
9.
Telemed J E Health ; 24(3): 203-209, 2018 03.
Artigo em Inglês | MEDLINE | ID: mdl-28686082

RESUMO

PURPOSE: Veterans with dementia and their caregivers in remote areas may not have access to specialists to provide diagnosis, treatment, and education. The purpose of this clinical demonstration project was to examine the feasibility, acceptability, and impact of a video consultations clinic for veterans with dementia or memory complaints and their caregivers. METHODS: The dementia clinical video telehealth (CVT) consultation clinic was established to identify, diagnose, and treat dementia in veterans at sites distant from the main medical center. A geriatrician at the main facility provided video consultation to patients and caregivers at seven satellite facilities. Diagnoses made and services provided were recorded after the initial consultation. Patient and caregiver satisfaction with the CVT clinic were assessed. FINDINGS: Ninety-four patients were evaluated in the CVT dementia clinic (average age = 74.7; average Mini-Mental State Exam = 24.4). Forty patients had a prior dementia diagnosis, 15 received a new dementia diagnosis, and 20 a new mild cognitive impairment diagnosis. Of the remaining patients evaluated for memory complaints, seven were found to have depression, three had hearing loss, and three had traumatic brain injury. After CVT consultation, common referrals included social work (n = 43), neuropsychology (n = 36), and brain imaging (n = 26). Patients and caregivers expressed high satisfaction with the video consultation and 90% of caregivers indicated they would rather use CVT than travel to see the specialist in person. CONCLUSIONS: Video consultation was well accepted by both dementia patients and caregivers. CVT may facilitate timely diagnosis and management and provide support for rural dementia patients and caregivers.


Assuntos
Demência/diagnóstico , Demência/terapia , Satisfação do Paciente , Consulta Remota/organização & administração , População Rural , Adulto , Idoso , Idoso de 80 Anos ou mais , Lesões Encefálicas Traumáticas/diagnóstico , Lesões Encefálicas Traumáticas/terapia , Cuidadores/psicologia , Disfunção Cognitiva/diagnóstico , Disfunção Cognitiva/terapia , Depressão/diagnóstico , Depressão/terapia , Feminino , Perda Auditiva/diagnóstico , Humanos , Masculino , Testes de Estado Mental e Demência , Pessoa de Meia-Idade , Encaminhamento e Consulta , Veteranos , Comunicação por Videoconferência
10.
Telemed J E Health ; 24(12): 1006-1013, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-29672218

RESUMO

Background:We studied the feasibility of using the Veteran Health Administration's electronic health record (EHR), My HealtheVet, as an educational and monitoring tool for veterans with heart failure (HF).Methods:We enrolled 120 HF patients with a mean age (±standard deviation): 64.8 ± 9.6, range: 41-91 years. There were 105 (87.5%) non-Hispanics, 15 (12.5%) Hispanics, 91 (75.8%) whites, and 20 (16.5%) blacks, and 62 (51.7%) were married. Study participants received educational material on managing their HF and were monitored on their weight and HF symptoms weekly. Surveys on My HealtheVet use and secondary outcomes including knowledge of their illness, quality of life (QoL), and self-efficacy were conducted at baseline and 26 weeks after enrollment.Results:Among the participants, 55 (45.8%) had used My HealtheVet. The number of weeks each user responded to the weekly messages by the care coordinator ranged from 1 (4%) to 26 (100%) with a median of 8. Secondary outcome data were available for 54 patients (24 users and 30 nonusers) who participated in both baseline and 26-week surveys. There was a significant improvement in QoL (p < 0.01) among users of My HealtheVet compared with nonusers. There were no significant differences with respect to self-efficacy or HF knowledge. Use of My HealtheVet and ease in using the HealtheVet portal increased from baseline to follow-up.Conclusions:EHR-based interventions have potential for HF monitoring and case management, and may be feasible in improving QoL for patients.


Assuntos
Registros Eletrônicos de Saúde/organização & administração , Conhecimentos, Atitudes e Prática em Saúde , Insuficiência Cardíaca/terapia , Educação de Pacientes como Assunto/organização & administração , Veteranos , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Insuficiência Cardíaca/fisiopatologia , Insuficiência Cardíaca/psicologia , Humanos , Masculino , Pessoa de Meia-Idade , Qualidade de Vida , Autoeficácia , Estados Unidos , United States Department of Veterans Affairs
11.
Langmuir ; 33(14): 3404-3412, 2017 04 11.
Artigo em Inglês | MEDLINE | ID: mdl-28328229

RESUMO

Major developments in concrete technology have been achieved with the use of polycarboxylate-based superplasticizers (PCEs) to improve the concrete rheology without increasing the mix water content. Currently, it is possible to control the fluidity of the fresh concrete and obtain stronger and more durable structures. Therefore, there is a strong incentive to understand the interactions between PCEs and cement hydrates at the atomic scale to design new customized functional PCEs according to the ever-increasing requirements of the concrete industry. Here, the bonding types generated between a PCE with silyl functionalities (PCE-Sil) and a synthetic calcium silicate hydrate (C-S-H) are analyzed using XRD, 29Si NMR spectroscopy, and synchrotron-based techniques, such as NEXAFS and EXAFS. The results indicated that the carboxylic groups present in PCE-Sil interact by a ligand-type bond with calcium, which modified not only the symmetry and coordination number of the calcium located at the surface of C-S-H but also the neighboring silicon atoms of the C-S-H. In addition, the silyl functionalities of the PCE-Sil generated covalent bonds through siloxane bridges between the silanol groups of PCE-Sil and the nonbonding oxygen located at the dimeric sites in C-S-H, forming new bridging silicon sites and subsequently increasing the silicate polymerization.

12.
Phys Chem Chem Phys ; 19(2): 1571-1579, 2017 Jan 04.
Artigo em Inglês | MEDLINE | ID: mdl-27990527

RESUMO

A comprehensive study of acetylene adsorption on δ-MoC(001), TiC(001) and ZrC(001) surfaces was carried out by means of calculations based on periodic density functional theory, using the Perdew-Burke-Ernzerhof exchange-correlation functional. It was found that the bonding of acetylene was significantly affected by the electronic and structural properties of the carbide surfaces. The adsorbate interacted with metal and/or carbon sites of the carbide. The interaction of acetylene with the TiC(001) and ZrC(001) surfaces was strong (binding energies higher than -3.5 eV), while moderate acetylene adsorption energies were observed on δ-MoC(001) (-1.78 eV to -0.66 eV). Adsorption energies, charge density difference plots and Mulliken charges suggested that the binding of the hydrocarbon to the surface had both ionic and covalent contributions. According to the C-C bond lengths obtained, the adsorbed molecule was modified from acetylene-like into ethylene-like on the δ-MoC(001) surface (desired behavior for hydrogenation reactions) but into ethane-like on TiC(001) and ZrC(001). The obtained results suggest that the δ-MoC(001) surface is expected to have the best performance in selective hydrogenation reactions to convert alkynes into alkenes. Another advantage of δ-MoC(001) is that, after C2H2 adsorption, surface carbon sites remain available, which are necessary for H2 dissociation. However, these sites were occupied when C2H2 was adsorbed on TiC(001) and ZrC(001), limiting their application in the hydrogenation of alkynes.

13.
Telemed J E Health ; 23(7): 544-554, 2017 07.
Artigo em Inglês | MEDLINE | ID: mdl-28051761

RESUMO

BACKGROUND: Chronic heart failure (HF) is a complex and costly disease. Daily weight and symptom monitoring is the cornerstone of HF management. Little information exists about feasibility of a mobile monitoring intervention among minority patients with HF. METHODS: We developed and tested usability of a mobile-monitoring system in minority patients with HF in a 2:1 randomized controlled trial. We tracked usage and obtained feedback on usability and the system overall at 1, 2, and 3 months. RESULTS: Forty-two participants aged 53.0 ± 9.4 years (mean ± standard deviation) were randomized to the mobile-monitoring intervention group. They included the following: 67% males, 76% White Hispanics, 21% African Americans, and 52% with high school education or less. Over the 3-month intervention period, 26 (62%) participants used the system over 50% of the time. Overall, on a 1.0-7.0 scale for both, program satisfaction scores were excellent (mean 6.84 ± 0.46), and the usability ratings were all above 6.0. Comparing 1- to 3-month responses, there was a substantial increase in the percentage of participants who felt the system was easy to use after they had gotten used to it (84% vs. 94%) and that navigating the system was not complicated (78% vs. 84%). Almost all participants said that the program made them feel more secure about their health and that they would stay enrolled in a program like this. None of them had used a similar system before. CONCLUSIONS: A mobile phone-based disease management program is feasible in a minority county hospital population and offers a modality to help reduce ethnic disparity.


Assuntos
Telefone Celular , Doença Crônica/terapia , Insuficiência Cardíaca/diagnóstico , Insuficiência Cardíaca/terapia , Grupos Minoritários/estatística & dados numéricos , Satisfação do Paciente/estatística & dados numéricos , Telemedicina , Adulto , Negro ou Afro-Americano/estatística & dados numéricos , Idoso , Idoso de 80 Anos ou mais , Feminino , Hispânico ou Latino/estatística & dados numéricos , Hospitais de Condado/estatística & dados numéricos , Hospitais Urbanos/estatística & dados numéricos , Humanos , Masculino , Pessoa de Meia-Idade , Monitorização Fisiológica/métodos , Inquéritos e Questionários , Estados Unidos , População Urbana/estatística & dados numéricos , População Branca/estatística & dados numéricos
14.
Clin Exp Pharmacol Physiol ; 41(5): 325-30, 2014 May.
Artigo em Inglês | MEDLINE | ID: mdl-24606242

RESUMO

Postural tachycardia syndrome (POTS) is characterized by excessive increases in heart rate (HR) upon standing. Previous studies have shown that standing HR decreases over time in POTS patients given placebo. We hypothesized that this reduction is due to cardiovascular physiological alteration, as opposed to psychological benefit from perceived therapy. To prospectively test this hypothesis, we examined the effects of an open-label 'no treatment' intervention (NoRx) compared with a patient-blinded placebo on standing HR in POTS patients. Twenty-one POTS patients participated in a randomized cross-over trial with oral placebo versus NoRx administered at 0900 h. Seated blood pressure (BP) and HR were measured at baseline and every hour for 4 h. Similarly, BP and HR were measured while patients stood for 10 min at these time points. Standing HR decreased significantly over time with both NoRx (112±13 and 103±16 b.p.m. at baseline and 4 h, respectively) and placebo (112±14 and 102±16 b.p.m. at baseline and 4 h, respectively; Ptime<0.001), but this effect was not different between interventions (Pdrug=0.771). Postural tachycardia syndrome patients have exaggerated orthostatic tachycardia in the morning that decreases over time with either placebo or NoRx interventions, suggesting this phenomenon is due to cardiovascular physiological variation. These data highlight the need for a placebo arm in haemodynamic clinical trials in POTS and may have important implications for the diagnosis of these patients.


Assuntos
Fenômenos Fisiológicos Cardiovasculares , Efeito Placebo , Síndrome da Taquicardia Postural Ortostática/tratamento farmacológico , Postura , Adulto , Análise de Variância , Pressão Sanguínea/fisiologia , Ritmo Circadiano/fisiologia , Estudos Cross-Over , Feminino , Frequência Cardíaca/fisiologia , Humanos , Masculino , Placebos/administração & dosagem , Síndrome da Taquicardia Postural Ortostática/fisiopatologia , Síndrome da Taquicardia Postural Ortostática/psicologia , Estudos Prospectivos , Fatores de Tempo
15.
Adv Genet ; 111: 1-79, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38908897

RESUMO

This chapter overviews genetic techniques' fundamentals and methodological features, including different approaches, analyses, and applications that have contributed to advancing health and disease. The aim is to describe laboratory methodologies and analyses employed to understand the genetic landscape of different biological contexts, from conventional techniques to cutting-edge technologies. Besides describing detailed aspects of the polymerase chain reaction (PCR) and derived types as one of the principles for many novel techniques, we also discuss microarray analysis, next-generation sequencing, and genome editing technologies such as transcription activator-like effector nucleases (TALENs) and the clustered regularly interspaced short palindromic repeats (CRISPR) and CRISPR-associated (Cas) systems. These techniques study several phenotypes, ranging from autoimmune disorders to viral diseases. The significance of integrating diverse genetic methodologies and tools to understand host genetics comprehensively and addressing the ethical, legal, and social implications (ELSI) associated with using genetic information is highlighted. Overall, the methods, procedures, and applications in host genetic analysis provided in this chapter furnish researchers and practitioners with a roadmap for navigating the dynamic landscape of host-genome interactions.


Assuntos
Sistemas CRISPR-Cas , Humanos , Sistemas CRISPR-Cas/genética , Edição de Genes/métodos , Sequenciamento de Nucleotídeos em Larga Escala
16.
Biomedica ; 44(Sp. 1): 101-109, 2024 05 31.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-39079144

RESUMO

INTRODUCTION: Low-cost, accurate high-risk HPV tests are needed for cervical cancer screening in limited-resource settings. OBJECTIVE: To compare the performance of the low-cost Hybribio-H13 test with the Hybrid Capture® 2 to detect cervical intraepithelial neoplasia grade 2 or 3 (CIN2 and CIN3). MATERIALS AND METHODS: Archived baseline samples tested by the Hybrid Capture® 2 from women of the ASCUS-COL trial, aged 20 to 69 years, with biopsy-colposcopy directed diagnosis of CIN2+ (n = 143), CIN3+ (n = 51), and < CIN2 (n = 632) were blindly tested by the Hybribio-H13 test. RESULTS: The relative sensitivity of the Hybribio-H13 test versus the Hybrid Capture® 2 for detecting CIN2+ was 0.89 (90% CI = 0,80-0,98; NIT = 0,66), and for CIN3+ was 0,92 (90% CI = 0,85-0,98; NIT = 0,35). Relative specificity was 1.19 (90% CI = 1.05-1.33; NIT <0.00001). In the analysis restricted to women older than 30 years, the relative sensitivity of the Hybribio-H13 for CIN3+ was marginally below unity (ratio = 0.97; 90% CI = 0.95-0.99), and the specificity remained higher than the Hybrid Capture® 2 test. CONCLUSION: The Hybribio-H13 test was as specific as the Hybrid Capture® 2 for detecting CIN2+ or CIN3+ but less sensitive. Considering these results and the young age of the population recruited for screening because of ASCUS cytology, we suggest our results warrant the evaluation of the Hybribio-H13 for screening cervical cancer, especially in the evaluated population.


Introducción. Se necesitan pruebas para detectar genotipos de VPH de alto riesgo, precisas y de bajo costo, para la tamización del cáncer de cuello uterino en entornos de recursos limitados. Objetivo. Comparar el desempeño de la prueba de bajo costo Hybrid-H13 con la de Hybrid Capture® 2 para detectar NIC2+ y NIC3+. Materiales y métodos. Se analizaron en ciego muestras de la línea base provenientes de mujeres del estudio ASCUS-COL, entre los 20 y los 69 años, con diagnóstico dirigido por biopsia-colposcopia de NIC2+ (n = 143), NIC3 + (n = 51) y < NIC2 (n = 632) con la prueba para detección de virus de papiloma humano Hybribio-H13. Estas muestras fueron previamente evaluadas con la prueba Hybrid Capture® 2. Resultados. La sensibilidad relativa de Hybribio-13 versus la de Hybrid Capture® 2 para detectar NIC2+ fue de 0,89 (IC90%: 0,80-0,98; NIT = 0,66) y para NIC3+ fue de 0,92 (IC90%: 0,85-0,98; NIT = 0,35). La especificidad relativa fue de 1,19 (IC90%: 1,05-1,33; NIT <0,00001). En el análisis restringido a mujeres mayores de 30 años, la sensibilidad relativa de Hybribio-H13 para NIC3+ estuvo marginalmente por debajo de la unidad (proporción = 0,97; IC90%: 0,95-0,99) y la especificidad permaneció más alta que la de la prueba Hybrid Capture® 2. Conclusión. La prueba de Hybribio-H13 fue tan específica como la de Hybrid Capture® 2, pero menos sensible para detectar NIC2+ o NIC3+. Teniendo en cuenta estos resultados y la temprana edad de la población reclutada en la tamización por la presencia de ASCUS en la citología, se sugiere continuar con la evaluación de la prueba Hybribio-H13 para la detección de cáncer de cuello uterino en poblaciones con las mismas características que las de la aquí evaluada.


Assuntos
Infecções por Papillomavirus , Sensibilidade e Especificidade , Displasia do Colo do Útero , Neoplasias do Colo do Útero , Humanos , Feminino , Displasia do Colo do Útero/diagnóstico , Displasia do Colo do Útero/virologia , Pessoa de Meia-Idade , Adulto , Neoplasias do Colo do Útero/diagnóstico , Neoplasias do Colo do Útero/virologia , Idoso , Infecções por Papillomavirus/diagnóstico , Adulto Jovem , Detecção Precoce de Câncer/métodos , Papillomaviridae/genética , Papillomaviridae/isolamento & purificação , Papillomavirus Humano
17.
Zookeys ; 1192: 9-27, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38419745

RESUMO

The first freshwater amphibian representative of Crinocheta (Oniscidea) from the Neotropics is described from caves within the Brazilian Cerrado biome, state of Mato Grosso do Sul. Kadiweuoniscusrebellisgen. et sp. nov. is placed in the family Philosciidae. The present work represents a significant contribution to future studies seeking to understand the ecological and evolutionary processes of Crinocheta within the Neotropical region. Moreover, it highlights the importance of biodiversity surveys in subterranean environments toward effective conservation efforts of these unique habitats and their surroundings.

18.
R Soc Open Sci ; 10(10): 230917, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37830028

RESUMO

Colombia, renowned as an important centre of global biodiversity, continues to harbour undiscovered evolutionary hotspots of flowering plants. The altitude-dependent hypothesis suggests that richness patterns are determined by altitude and probably influenced by climate variables. This study employs null models based on a species-level phylogeny of Colombia's flowering plants and their geographical distributions to identify evolutionary hotspots. We explore the potential correlation between elevation, climate variables such as temperature and rainfall, and the location and nature of these hotspots. The findings reveal that evolutionary cradles, which house young endemic species, are predominantly located in the mountainous regions of the Andes. Conversely, evolutionary museums, hosting older endemic species, are found in lowland regions spanning the Caribbean, Orinoco, Amazon and Pacific areas. These results demonstrate a clear elevational segregation of evolutionary hotspots, primarily influenced by temperature, thereby supporting the hypothesis under examination. Furthermore, this study identifies previously unrecognized evolutionary regions, highlighting the limited understanding of Colombia's biodiversity distribution and evolutionary history.

19.
R Soc Open Sci ; 10(4): 230229, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-37063994

RESUMO

The Cinchona genus is important for humanity due to its ethnobotanical properties, and in particular its ability to prevent and treat malaria. However, there have been historical changes of Cinchona distribution in the tropical Andes that remain undocumented. In the late eighteenth and early nineteenth centuries, several explorers recorded Cinchona precise localities in present-day Colombia and Ecuador, countries which harbour about half of the species of the genus, including C. officinalis. We compare historical and twentieth-century records to evaluate whether elevational ranges, mean elevation and latitude varied between the two periods. A large expansion of 662.5 m in average elevation for Cinchona and 792.5 m in elevational range for C. officinalis was found. These findings have implications for the conservation of economically important species and help us understand the impacts of the Anthropocene over time.

20.
Biomolecules ; 13(7)2023 07 19.
Artigo em Inglês | MEDLINE | ID: mdl-37509183

RESUMO

Uveal melanoma (UVM) is a highly aggressive ocular cancer with limited therapeutic options and poor prognosis particularly for patients with liver metastasis. As such, the identification of new prognostic biomarkers is critical for developing effective treatment strategies. In this study, we aimed to investigate the potential of an ultraviolet light response gene signature to predict the prognosis of UVM patients. Our approach involved the development of a prognostic model based on genes associated with the cellular response to UV light. By employing this model, we generated risk scores to stratify patients into high- and low-risk groups. Furthermore, we conducted differential expression analysis between these two groups and explored the estimation of immune infiltration. To validate our findings, we applied our methodology to an independent UVM cohort. Through our study, we introduced a novel survival prediction tool and shed light on the underlying cellular processes within UVM tumors, emphasizing the involvement of immune subsets in tumor progression.


Assuntos
Melanoma , Neoplasias Uveais , Humanos , Raios Ultravioleta , Melanoma/patologia , Neoplasias Uveais/genética , Neoplasias Uveais/metabolismo , Neoplasias Uveais/patologia , Olho/metabolismo
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