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1.
Proc Natl Acad Sci U S A ; 119(27): e2202310119, 2022 07 05.
Artículo en Inglés | MEDLINE | ID: mdl-35759674

RESUMEN

Human activities pose a major threat to tropical forest biodiversity and ecosystem services. Although the impacts of deforestation are well studied, multiple land-use and land-cover transitions (LULCTs) occur in tropical landscapes, and we do not know how LULCTs differ in their rates or impacts on key ecosystem components. Here, we quantified the impacts of 18 LULCTs on three ecosystem components (biodiversity, carbon, and soil), based on 18 variables collected from 310 sites in the Brazilian Amazon. Across all LULCTs, biodiversity was the most affected ecosystem component, followed by carbon stocks, but the magnitude of change differed widely among LULCTs and individual variables. Forest clearance for pasture was the most prevalent and high-impact transition, but we also identified other LULCTs with high impact but lower prevalence (e.g., forest to agriculture). Our study demonstrates the importance of considering multiple ecosystem components and LULCTs to understand the consequences of human activities in tropical landscapes.


Asunto(s)
Efectos Antropogénicos , Biodiversidad , Conservación de los Recursos Naturales , Bosque Lluvioso , Agricultura , Brasil , Carbono , Humanos
2.
Pharmacogenet Genomics ; 34(4): 91-104, 2024 Jun 01.
Artículo en Inglés | MEDLINE | ID: mdl-38682317

RESUMEN

OBJECTIVES: This study explored the association of deleterious variants in pharmacodynamics (PD) genes with statin response and adverse effects in patients with familial hypercholesterolemia (FH) and analyzed their potential effects on protein structure and stability. METHODS: Clinical and laboratory data were obtained from 144 adult FH patients treated with statins. A panel of 32 PD genes was analyzed by exon-targeted gene sequencing. Deleterious variants were identified using prediction algorithms and their structural effects were analyzed by molecular modeling studies. RESULTS: A total of 102 variants were predicted as deleterious (83 missense, 8 stop-gain, 4 frameshift, 1 indel, 6 splicing). The variants ABCA1 rs769705621 (indel), LPA rs41267807 (p.Tyr2023Cys) and KIF6 rs20455 (p.Trp719Arg) were associated with reduced low-density lipoprotein cholesterol (LDLc) response to statins, and the LPL rs1801177 (p.Asp36Asn) with increased LDLc response (P < 0.05). LPA rs3124784 (p.Arg2016Cys) was predicted to increase statin response (P = 0.022), and ABCA1 rs769705621 to increase the risk of statin-related adverse events (SRAE) (P = 0.027). LPA p.Arg2016Cys and LPL p.Asn36Asp maintained interactions with solvent, LPA p.Tyr2023Cys reduced intramolecular interaction with Gln1987, and KIF6 p.Trp719Arg did not affect intramolecular interactions. DDMut analysis showed that LPA p.Arg2016Cys and p.Tyr2023Cys and LPL p.Asp36Asn caused energetically favorable changes, and KIF6 p.Trp719Arg resulted in unfavorable energetic changes, affecting protein stability. CONCLUSION: Deleterious variants in ABCA1, LPA, LPL and KIF6 are associated with variability in LDLc response to statins, and ABCA1 rs769705621 is associated with SRAE risk in FH patients. Molecular modeling studies suggest that LPA p.Tyr2023Cys and KIF6 p.Trp719Arg disturb protein conformational structure and stability.


Asunto(s)
Transportador 1 de Casete de Unión a ATP , Inhibidores de Hidroximetilglutaril-CoA Reductasas , Hiperlipoproteinemia Tipo II , Cinesinas , Lipoproteína Lipasa , Humanos , Cinesinas/genética , Masculino , Femenino , Persona de Mediana Edad , Inhibidores de Hidroximetilglutaril-CoA Reductasas/efectos adversos , Hiperlipoproteinemia Tipo II/genética , Hiperlipoproteinemia Tipo II/tratamiento farmacológico , Transportador 1 de Casete de Unión a ATP/genética , Lipoproteína Lipasa/genética , Adulto , Estabilidad Proteica , LDL-Colesterol/sangre , Polimorfismo de Nucleótido Simple
3.
J Toxicol Environ Health B Crit Rev ; 27(4): 131-152, 2024 May 18.
Artículo en Inglés | MEDLINE | ID: mdl-38480528

RESUMEN

The aim of this review was to explore the advances of nanoformulations as a strategy to optimize glioblastoma treatment, specifically focusing on targeting and controlling drug delivery systems to the tumor. This review followed the PRISMA recommendations. The studies were selected through a literature search conducted in the electronic databases PubMed Central, Science Direct, Scopus and Web of Science, in April 2023, using the equation descriptors: (nanocapsule OR nanoformulation) AND (glioblastoma). Forty-seven investigations included were published between 2011 and 2023 to assess the application of different nanoformulations to optimize delivery of chemotherapies including temozolomide, carmustine, vincristine or cisplatin previously employed in brain tumor therapy, as well as investigating another 10 drugs. Data demonstrated the possible application of different matrices employed as nanocarriers and utilization of functionalizing agents to improve internalization of chemotherapeutics. Functionalization was developed with the application of peptides, micronutrients/vitamins, antibodies and siRNAs. Finally, this review demonstrated the practical and clinical application of nanocarriers to deliver multiple drugs in glioblastoma models. These nanomodels might ideally be developed using functionalizing ligand agents that preferably act synergistically with the drug these agents carry. The findings showed promising results, making nanoformulations one of the best prospects for innovation and improvement of glioblastoma treatment.


Asunto(s)
Neoplasias Encefálicas , Glioblastoma , Humanos , Glioblastoma/tratamiento farmacológico , Glioblastoma/patología , Temozolomida/uso terapéutico , Carmustina/uso terapéutico , Neoplasias Encefálicas/tratamiento farmacológico , Neoplasias Encefálicas/patología , Sistemas de Liberación de Medicamentos/métodos
4.
Health Econ ; 33(1): 3-11, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-37796738

RESUMEN

In this paper, we investigate whether skin color is a source of inequality in women's health by exploring the longitudinal framework of the PCSVDFMulher survey in Northeast Brazil. Specifically, we measure the skin color gradient in women's general and mental health, as well as in showing health risk behavior. We find that darker-skinned women show poorer mental health outcomes and a higher likelihood of drinking and smoking more frequently than their lighter-skinned counterparts. The skin color gradient is persistent and systematic, even when modeling different sources of unobserved heterogeneity and accounting for the existing socioeconomic inequalities and racial identity. We also find that racial identity is an important source of heterogeneous responses of women's health to skin tone.


Asunto(s)
Pigmentación de la Piel , Salud de la Mujer , Femenino , Humanos , Brasil/epidemiología , Encuestas y Cuestionarios , Salud Mental , Factores Socioeconómicos
5.
Mol Biol Rep ; 50(11): 9165-9177, 2023 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-37776414

RESUMEN

BACKGROUND: Familial hypercholesterolemia (FH) is caused by pathogenic variants in low-density lipoprotein (LDL) receptor (LDLR) or its associated genes, including apolipoprotein B (APOB), proprotein convertase subtilisin/kexin type 9 (PCSK9), and LDLR adaptor protein 1 (LDLRAP1). However, approximately 40% of the FH patients clinically diagnosed (based on FH phenotypes) may not carry a causal variant in a FH-related gene. Variants located at 3' untranslated region (UTR) of FH-related genes could elucidate mechanisms involved in FH pathogenesis. This study used a computational approach to assess the effects of 3'UTR variants in FH-related genes on miRNAs molecular interactions and to explore the association of these variants with molecular diagnosis of FH. METHODS AND RESULTS: Exons and regulatory regions of FH-related genes were sequenced in 83 FH patients using an exon-target gene sequencing strategy. In silico prediction tools were used to study the effects of 3´UTR variants on interactions between miRNAs and target mRNAs. Pathogenic variants in FH-related genes (molecular diagnosis) were detected in 44.6% FH patients. Among 59 3'UTR variants identified, LDLR rs5742911 and PCSK9 rs17111557 were associated with molecular diagnosis of FH, whereas LDLR rs7258146 and rs7254521 and LDLRAP1 rs397860393 had an opposite effect (p < 0.05). 3´UTR variants in LDLR (rs5742911, rs7258146, rs7254521) and PCSK9 (rs17111557) disrupt interactions with several miRNAs, and more stable bindings were found with LDLR (miR-4435, miR-509-3 and miR-502) and PCSK9 (miR-4796). CONCLUSION: LDLR and PCSK9 3´UTR variants disturb miRNA:mRNA interactions that could affect gene expression and are potentially associated with molecular diagnosis of FH.


Asunto(s)
Hiperlipoproteinemia Tipo II , MicroARNs , Humanos , Proproteína Convertasa 9/genética , Regiones no Traducidas 3'/genética , MicroARNs/genética , Hiperlipoproteinemia Tipo II/genética , Hiperlipoproteinemia Tipo II/diagnóstico , Receptores de LDL/genética , Mutación
6.
J Clin Periodontol ; 50(8): 1123-1137, 2023 08.
Artículo en Inglés | MEDLINE | ID: mdl-37257917

RESUMEN

BACKGROUND: Periodontitis worsens the hyperglycaemia in patients with type 2 diabetes mellitus (T2DM). Subgingival instrumentation, with or without surgical access, is the gold-standard treatment for periodontitis. The aim was to summarize the evidence on the effect of subgingival instrumentation (with or without open flap) on the reduction of glycosylated haemoglobin (HbA1c). METHODS: Nine electronic databases were searched up to 15 February 2023. Twelve randomized controlled trials with at least 6 months of follow-up were included. Studies using systemic or local-delivery antimicrobial therapies were excluded. Meta-analyses were performed using the random-effects model. The sources of heterogeneity were assessed by applying linear meta-regression. Risk of bias was assessed by RoB 2, and certainty of evidence by GRADE. RESULTS: Eleven studies were included in the quantitative analyses (1374 patients). Subgingival instrumentation resulted in 0.29% lower HbA1c (95% confidence interval: 0.10-0.47; p = .03) compared with non-active treatment. DISCUSSION: None of the 12 studies were assessed as having low risk of bias. The percentage of females and the time of diabetes diagnosis significantly explained the high level of heterogeneity. Subgingival periodontal therapy results in a significant and clinically relevant improvement in glycaemic control over 6 months in patients with T2DM and periodontitis. The grade of evidence was moderate.


Asunto(s)
Diabetes Mellitus Tipo 2 , Periodontitis , Femenino , Humanos , Diabetes Mellitus Tipo 2/complicaciones , Hemoglobina Glucada , Control Glucémico , Estudios de Seguimiento , Raspado Dental/métodos , Ensayos Clínicos Controlados Aleatorios como Asunto , Periodontitis/complicaciones , Periodontitis/terapia
7.
J Toxicol Environ Health A ; 86(4): 87-102, 2023 02 16.
Artículo en Inglés | MEDLINE | ID: mdl-36756732

RESUMEN

The aim of this study was to determine the oxidative/antioxidative effects, modulatory and selective potential of α-tocopherol (vitamin E) on antineoplastic drug-induced toxicogenetic damage. The toxicity, cytotoxicity and genotoxicity induced by antineoplastic agents cyclophosphamide (CPA) and doxorubicin (DOX) was examined utilizing as models Saccharomyces cerevisiae, Allium cepa, Artemia salina and human peripheral blood mononuclear cells (PBMCs) in the presence of α-tocopherol. For these tests, concentrations of α- tocopherol 100 IU/ml (67mg/ml), CPA 20 µg/ml, DOX 2 µg/ml were used. The selectivity of α-tocopherol was assessed by the MTT test using human mammary gland non-tumor (MCF10A) and tumor (MCF-7) cell lines. Data showed cytoplasmic and mitochondrial oxidative damage induced by CPA or DOX was significantly diminished by α-tocopherol in S. cerevisiae. In addition, the toxic effects on A. salina and cytotoxic and mutagenic effects on A. cepa were significantly reduced by α-tocopherol. In PBMCs, α-tocopherol alone did not markedly affect these cells, and when treated in conjunction with CPA or DOX, α-tocopherol reduced the toxicogenetic effects noted after antineoplastic drug administration as evidenced by decreased chromosomal alterations and lowered cell death rate. In human mammary gland non-tumor and tumor cell lines, α-tocopherol produced selective cytotoxicity with 2-fold higher effect in tumor cells. Evidence indicates that vitamin E (1) produced anti-cytotoxic and anti-mutagenic effects against CPA and DOX (2) increased higher selectivity toward tumor cells, and (3) presented chemoprotective activity in PBMCs.


Asunto(s)
Antineoplásicos , alfa-Tocoferol , Humanos , alfa-Tocoferol/farmacología , Saccharomyces cerevisiae , Leucocitos Mononucleares , Antineoplásicos/toxicidad , Antineoplásicos/uso terapéutico , Doxorrubicina/toxicidad , Ciclofosfamida/toxicidad , Vitamina E
8.
Rheumatol Int ; 43(10): 1799-1810, 2023 10.
Artículo en Inglés | MEDLINE | ID: mdl-37354245

RESUMEN

There is a paucity of studies assessing multidisciplinary interventions focused on tackling physical inactivity/sedentary behavior and poor dietary habits in SLE. The Living well with Lupus (LWWL) is a randomized controlled trial to investigate whether a six-month lifestyle change intervention will improve cardiometabolic risk factors (primary outcome) among systemic lupus erythematosus (SLE) patients with low disease activity (SLEDAI score ≤ 4) and with high cardiovascular risk. As secondary goals, we will evaluate: (1) the intervention's safety, efficacy, and feasibility in promoting lifestyle changes, and (2) the effects of the intervention on secondary outcomes (i.e., clinical parameters, functional capacity, fatigue, psychological aspects, sleep quality and health-related quality of life). Patients will be randomly allocated to either a control (i.e., standard care) or a lifestyle intervention group using a simple randomization (1:1 ratio, blocks of 20). Mixed Model analyses will be conducted for comparing groups following an intention-to-treat approach. A per protocol analysis will also be conducted. This study has the potential to generate new, clinically relevant data able to refine the multidisciplinary management of SLE patients. Protocol version number: NCT04431167 (first version).


Asunto(s)
Lupus Eritematoso Sistémico , Calidad de Vida , Humanos , Dieta Saludable , Ejercicio Físico , Lupus Eritematoso Sistémico/tratamiento farmacológico , Estilo de Vida , Ensayos Clínicos Controlados Aleatorios como Asunto
9.
An Acad Bras Cienc ; 95(suppl 1): e20220415, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37466534

RESUMEN

In Compost-Bedded Pack Barn (CBP) systems, air velocity is linked with the thermal comfort of housed dairy cattle and bedding quality and, therefore, assessing ventilation efficiency is essential. In this context, the objective of this study was to evaluate and characterize dependence and spatial distribution of air velocity at the 1.5 m height (vair,M) and at bedding level (vair,B) in an open CBP system with positive pressure ventilation. The study was conducted in 2021, in a facility located in the Zona da Mata region, Minas Gerais, Brazil. The facility area was divided into a mesh composed of 55 equidistant points, where vair,M and vair,B data were collected in the morning (09:00 a.m.) and afternoon (03:00 p.m.) periods, during three weeks in Brazilian winter. Geostatistics techniques were used to assess dependence and spatial distribution. In both periods evaluated, there were a strong occurrence of spatial dependence and non-uniform vair,M and vair,B distributions. The vair,M and vair,B values were lower than recommended (1.8 m∙s-1) in more than 65.0% of the area. Adequate ventilation levels were observed only in the first 20.0 m of the facility, from Southeast to Northwest, because of the fan lines present.


Asunto(s)
Compostaje , Bovinos , Animales , Vivienda para Animales , Industria Lechera , Respiración con Presión Positiva , Estaciones del Año
10.
Knee Surg Sports Traumatol Arthrosc ; 31(6): 2412-2417, 2023 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-36208341

RESUMEN

PURPOSE: To describe the femoral insertion of the ACL using the posterior proximal cartilage of the lateral femoral condyle as the anatomical reference. METHODS: Twenty knees were dissected. The X-axis (deep-shallow) and Y-axis (high-low) were determined using the femoral diaphysis and the proximal cartilage of the lateral femoral condyle (point C) as a reference, which were easily identified by direct visualization through the anteromedial portal. The distances to the center of the anteromedial and posterolateral bands and to the center of the ACL were measured. RESULTS: The mean distances were 7.2 mm (SD: 0.7) between the center of the anteromedial bundle and the Y-axis (AM-Y), 9 mm (SD: 1.1) between the center of the ACL and the Y-axis (M-Y), and 12.7 mm (SD: 0.9) between the center of the posterolateral bundle and the Y-axis (PL-Y). Regarding the distance (from point C to the distal cartilage along the X-axis), the center of the anteromedial bundle (AM) was 35% (SD: 4.9%), the center of the posterolateral bundle was 62% (SD: 3.7%), and the center of the ACL (M) was 44% (SD: 7%) of the CD distance on average. CONCLUSION: Given the similarity among the specimens in terms of the height of the ACL on the Y-axis in relation to the proximal posterior cartilage of the femoral lateral condyle (point C), this point can be used as an arthroscopic intraoperative parameter to define the position of the femoral tunnel in ACL reconstruction for single- or double-bundle techniques.


Asunto(s)
Ligamento Cruzado Anterior , Articulación de la Rodilla , Humanos , Ligamento Cruzado Anterior/cirugía , Cadáver , Articulación de la Rodilla/cirugía , Fémur/cirugía , Cartílago , Tibia/cirugía
11.
Int J Behav Nutr Phys Act ; 19(1): 36, 2022 03 28.
Artículo en Inglés | MEDLINE | ID: mdl-35346232

RESUMEN

BACKGROUND: Understanding which strategies have been recommended for the promotion of active and healthy lifestyles through physical education (PE) classes can guide PE policies and practice. Therefore, we summarized worldwide recommendations regarding strategies for PE classes that have aimed to promote active and healthy lifestyles among school-aged children and adolescents. METHODS: The Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR) guidelines were utilized. A literature search was carried out in June 2020 in eight peer-reviewed literature databases, in addition to searches in institutional and personal libraries. The eligibility criteria included any online document that included recommendations targeting any dimension of PE classes (e.g., policy and environment, curriculum, appropriate instruction, student assessment, and strategies that interact with PE) published since 2000. RESULTS: In total, 2,408 potentially eligible documents were screened. Of these, 63 were included in the final analysis. The recommended strategies were as follows: six referred to policy and environment (valuing PE, higher frequency and duration of classes, inclusive PE classes, mandatory daily classes, evaluation of PE classes, and qualified teachers), five to curriculum (structure, type of content, cross-cutting themes, and components that improve PE classes), four to appropriate instruction (promotion of physical activities, inclusion of social issues, employment of the use of innovative technologies, and organization of the teaching-learning process), and three to student assessment (understanding human movement concepts, evaluation of contents, and assessment methods to develop an active and healthy lifestyle). CONCLUSION: Twenty-one strategies recommended for PE classes linked to five dimensions aimed at different target populations were identified. Over half were linked to the dimensions of policy and environment and appropriate instruction. PE is recommended to be mandatory and valued at all educational levels, with weekly frequency that contributes to an active and healthy lifestyle. This review shows that guaranteeing different experiences beyond sports, improving social inclusion, using innovative technologies, and providing adequate materials and spaces to be important challenges and ways to guide policies, programs, and new research in this field of knowledge. Open Science Framework Registration: https://osf.io/harwq/.


Asunto(s)
Ejercicio Físico , Educación y Entrenamiento Físico , Adolescente , Niño , Curriculum , Estilo de Vida Saludable , Humanos , Políticas
12.
Health Econ ; 31(8): 1800-1804, 2022 08.
Artículo en Inglés | MEDLINE | ID: mdl-35607715

RESUMEN

Caesarean section (C-section) rates continue to rise globally. Yet, there is little consensus about the key determinants of rising C-section rates and the sources of variation in C-section rates across the world. While C-sections can save lives when medically justified, unnecessary surgical procedures can be harmful for women and babies. We show that a state-wide law passed in São Paulo (Brazil), which increased women's autonomy to choose to deliver via C-section even when not medically necessary, is associated with a 3% increase in overall C-section rates. This association was driven by a 5% increase in primary C-sections, rather than repeated C-sections. Since the law emphasizes women's autonomy, these results are consistent with mothers' demand being an important contributor to high C-section rates in this context.


Asunto(s)
Cesárea , Madres , Brasil , Femenino , Humanos , Embarazo , Procedimientos Innecesarios
13.
Nature ; 535(7610): 144-7, 2016 07 07.
Artículo en Inglés | MEDLINE | ID: mdl-27362236

RESUMEN

Concerted political attention has focused on reducing deforestation, and this remains the cornerstone of most biodiversity conservation strategies. However, maintaining forest cover may not reduce anthropogenic forest disturbances, which are rarely considered in conservation programmes. These disturbances occur both within forests, including selective logging and wildfires, and at the landscape level, through edge, area and isolation effects. Until now, the combined effect of anthropogenic disturbance on the conservation value of remnant primary forests has remained unknown, making it impossible to assess the relative importance of forest disturbance and forest loss. Here we address these knowledge gaps using a large data set of plants, birds and dung beetles (1,538, 460 and 156 species, respectively) sampled in 36 catchments in the Brazilian state of Pará. Catchments retaining more than 69­80% forest cover lost more conservation value from disturbance than from forest loss. For example, a 20% loss of primary forest, the maximum level of deforestation allowed on Amazonian properties under Brazil's Forest Code, resulted in a 39­54% loss of conservation value: 96­171% more than expected without considering disturbance effects. We extrapolated the disturbance-mediated loss of conservation value throughout Pará, which covers 25% of the Brazilian Amazon. Although disturbed forests retained considerable conservation value compared with deforested areas, the toll of disturbance outside Pará's strictly protected areas is equivalent to the loss of 92,000­139,000 km2 of primary forest. Even this lowest estimate is greater than the area deforested across the entire Brazilian Amazon between 2006 and 2015 (ref. 10). Species distribution models showed that both landscape and within-forest disturbances contributed to biodiversity loss, with the greatest negative effects on species of high conservation and functional value. These results demonstrate an urgent need for policy interventions that go beyond the maintenance of forest cover to safeguard the hyper-diversity of tropical forest ecosystems.


Asunto(s)
Biodiversidad , Conservación de los Recursos Naturales/métodos , Conservación de los Recursos Naturales/estadística & datos numéricos , Bosques , Actividades Humanas , Clima Tropical , Animales , Aves/fisiología , Brasil , Escarabajos/fisiología , Incendios/estadística & datos numéricos , Agricultura Forestal/estadística & datos numéricos , Plantas
14.
Int Orthop ; 46(4): 697-703, 2022 04.
Artículo en Inglés | MEDLINE | ID: mdl-35091753

RESUMEN

BACKGROUND: The origin of persistent pain and joint limitation after knee arthroplasty are controversial and difficult to diagnose. Knee arthroscopy is indicated when the results of routine evaluation tests are not clear. The purpose of this study was to determine through arthroscopy the cause of post-knee-arthroplasty pain symptoms in patients without a prior diagnosis of cause of pain. METHODS: This prospective case series study described the outcomes of 34 patients (35 knees) with pain and limited function in the arthroplastic joint, who underwent diagnostic and therapeutic arthroscopy. Patients were clinically evaluated using range-of-motion tests and the Lysholm, Hospital for Special Surgery (HSS) and Knee Society Score (KSS) scales. RESULTS: The procedure found cyclops in 17 knees, synovitis in 9 knees, arthrofibrosis in 6 knees, polyethylene wear with debris in two knees, and polyethylene bouncing in one knee with unicompartmental arthroplasty with a mobile polyethylene platform. It was effective for the relief of pain symptoms, with excellent or good outcomes in 80% of cases; there was a poor outcome in 11.43%, which maintained the presentation of pain and underwent revision arthroplasty, and, in 8.57%, did not undergo another surgery despite symptom persistence. CONCLUSIONS: Post-arthroplasty knee arthroscopy seems beneficial in patients with pain and without a pre-established diagnosis and who had already undergone conservative treatment unsuccessfully.


Asunto(s)
Artroplastia de Reemplazo de Rodilla , Prótesis de la Rodilla , Osteoartritis de la Rodilla , Artroplastia de Reemplazo de Rodilla/efectos adversos , Artroplastia de Reemplazo de Rodilla/métodos , Artroscopía/efectos adversos , Humanos , Articulación de la Rodilla/cirugía , Osteoartritis de la Rodilla/etiología , Osteoartritis de la Rodilla/cirugía , Dolor/etiología , Polietileno , Reoperación , Resultado del Tratamiento
15.
Int J Mol Sci ; 23(17)2022 Sep 03.
Artículo en Inglés | MEDLINE | ID: mdl-36077486

RESUMEN

The Zika virus protease NS2B-NS3 has a binding site formed with the participation of a H51-D75-S135 triad presenting two forms, active and inactive. Studies suggest that the inactive conformation is a good target for the design of inhibitors. In this paper, we evaluated the co-crystallized structures of the protease with the inhibitors benzoic acid (5YOD) and benzimidazole-1-ylmethanol (5H4I). We applied a protocol consisting of two steps: first, classical molecular mechanics energy minimization followed by classical molecular dynamics were performed, obtaining stabilized molecular geometries; second, the optimized/relaxed geometries were used in quantum biochemistry and molecular mechanics/Poisson-Boltzmann surface area (MM-PBSA) calculations to estimate the ligand interactions with each amino acid residue of the binding pocket. We show that the quantum-level results identified essential residues for the stabilization of the 5YOD and 5H4I complexes after classical energy minimization, matching previously published experimental data. The same success, however, was not observed for the MM-PBSA simulations. The application of quantum biochemistry methods seems to be more promising for the design of novel inhibitors acting on NS2B-NS3.


Asunto(s)
Infección por el Virus Zika , Virus Zika , Simulación de Dinámica Molecular , Péptido Hidrolasas/metabolismo , Inhibidores de Proteasas/química , Serina Endopeptidasas/metabolismo , Succinatos , Proteínas no Estructurales Virales/metabolismo , Virus Zika/metabolismo
16.
Eur J Neurol ; 28(8): 2669-2679, 2021 08.
Artículo en Inglés | MEDLINE | ID: mdl-34033182

RESUMEN

BACKGROUND: The relationship between Parkinson's disease (PD) and cardiovascular and cerebrovascular disease is not yet well established. Recent data suggest an increased risk of myocardial infarction and stroke in PD patients. Therefore, we designed a study to assess surrogate markers of cardiovascular and cerebrovascular risk in PD. METHODS: We conducted a case-control study comparing PD patients recruited from a Movement Disorders Unit with controls randomly invited from a primary healthcare center. All participants underwent a detailed clinical evaluation, including medical history, physical assessment, carotid ultrasound, blood and urine analysis, and 24-h ambulatory blood pressure monitoring. The primary outcome was the carotid intima-media thickness (CIMT). RESULTS: We included 102 participants in each study arm. No significant difference was found in the CIMT among groups (MD: 0.01, 95% CI: -0.02, 0.04). Carotid plaques were more frequent in PD patients (OR: 1.90, 95% CI: 1.02, 3.55), although the lipid profile was more favorable in this group (LDL MD: -18.75; 95% CI: -10.69, -26.81). Nocturnal systolic blood pressure was significantly higher in PD patients (MD: 4.37, 95% CI: 0.27, 8.47) and more than half of the PD patients were non-dippers or reverse dippers (OR: 1.83, 95% CI: 1.04, 3.20). CONCLUSION: We did not find a difference in CIMT between PD and controls. A higher frequency of carotid plaques and abnormal dipper profile supports the hypothesis that PD patients are not protected from cardiovascular and cerebrovascular disease.


Asunto(s)
Grosor Intima-Media Carotídeo , Enfermedad de Parkinson , Presión Sanguínea , Monitoreo Ambulatorio de la Presión Arterial , Estudios de Casos y Controles , Humanos , Enfermedad de Parkinson/complicaciones , Enfermedad de Parkinson/epidemiología , Factores de Riesgo
17.
Physiol Plant ; 173(1): 67-87, 2021 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-32767360

RESUMEN

Cadmium (Cd2+) soil pollution is a global environmental problem caused by the high toxicity of Cd. 24-Epibrassinolide (EBR) is a biodegradable plant steroid involved in response modulation to biotic and abiotic stresses. The aim of this study was to evaluate if the leaf-application of EBR improves the gas exchange and possible repercussions on leaf anatomy in young Eucalyptus urophylla plants exposed to Cd toxicity. The experiment involved six treatments, which included three Cd concentrations (0, 450, and 900 µM) and two EBR concentrations (0 and 100 nM, described as - EBR and + EBR, respectively). Plants exposed to Cd toxicity suffered decreases in leaf anatomical and gas exchange parameters. However, the plants treated with EBR + 900 µM Cd showed an increase of 46%, 40%, and 54% in the net photosynthetic rate, water-use efficiency, and instantaneous carboxylation efficiency, respectively. The EBR application-induced improvements in gas exchange parameters, causing beneficial effects on the photosynthetic apparatus, mainly the effective quantum yield of photosystem II (PSII) photochemistry and electron transport rate. Furthermore, this steroid mitigated the effect of Cd toxicity on leaf anatomical variables, more specifically palisade and spongy parenchyma, which are intrinsically related to stomatal density, and stimulated the net photosynthetic rate of plants.


Asunto(s)
Eucalyptus , Esteroides Heterocíclicos , Brasinoesteroides , Cadmio/toxicidad , Fotosíntesis , Hojas de la Planta , Esteroides Heterocíclicos/farmacología
18.
Nanotechnology ; 32(46)2021 Aug 25.
Artículo en Inglés | MEDLINE | ID: mdl-34311447

RESUMEN

In the last decade, transition metal dichalcogenides (TMDs) have been intensively synthesized/studied thus linking their morphological aspect to their physical properties, and consequently leading to the understanding of the possible benefits of defects in such materials. Nevertheless, for future applications, quantifying and identifying defects in TMDs is still a milestone to reach in order to better employ these materials in optoelectronic devices. Raman Spectroscopy has been successfully employed in graphene to quantify punctual or line defects. In this paper, we bombarded monolayer MoSe2with He ions and found out the existence of three defect activated Raman bands around 250-300 cm-1. Density functional theory calculations were employed to obtain the electronic and phonon dispersion bands, making it possible to infer that these bands arise from inter-valley Raman double resonance processes. Interestingly, the same punctual defect model, that allows one to predict the defect concentration at which graphene starts to become amorphous, also works for TMDs. Hence, this work opens the door to the macroscopic quantification of defects in TMDs, which is essential for technological applications.

19.
Exp Parasitol ; 222: 108062, 2021 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-33383024

RESUMEN

Long non-coding RNAs (lncRNAs) perform several types of regulatory functions and have been recently explored in the genus Schistosoma. Although sequencing and bioinformatics approaches have demonstrated the presence of hundreds of lncRNAs and microRNAs (miRNAs) in this genus, information regarding their abundance, characteristics, and potential functions linked to Schistosoma mansoni biology and parasite-host interaction is limited. Our objectives in the present study were to verify whether 15 previously identified S. mansoni lncRNAs are detectable in the host liver. In addition, we assess whether these lncRNAs are present in the S. mansoni infective form and the stages inside the definitive host. The detection of these 15 S. mansoni lncRNAs and a long terminal repeat (LTR) retrotransposon Saci 4 was performed in the eggs, cercariae, and 3.5-h schistosomula. All lncRNAs were found to be expressed in these stages; some of the lncRNAs were found in the livers of the infected C57BL/6 mice. In conclusion, S. mansoni lncRNAs were detected in host livers and quantified. Furthermore, many of the lncRNAs analyzed showed differential expression in the larval stages, indicating that they play a stage-specific regulatory role.


Asunto(s)
Hígado/parasitología , ARN Largo no Codificante/aislamiento & purificación , Schistosoma mansoni/genética , Esquistosomiasis mansoni/parasitología , Animales , Mapeo Cromosómico , Hígado/patología , Masculino , Ratones , Ratones Endogámicos C57BL , Reacción en Cadena en Tiempo Real de la Polimerasa , Retroelementos/fisiología , Transcripción Reversa , Schistosoma mansoni/crecimiento & desarrollo , Schistosoma mansoni/aislamiento & purificación , Esquistosomiasis mansoni/patología
20.
J Oral Maxillofac Surg ; 79(5): 981-988, 2021 May.
Artículo en Inglés | MEDLINE | ID: mdl-33561426

RESUMEN

PURPOSE: This study aimed to evaluate the anti-inflammatory effect of oral dexamethasone 4 mg in a single dose preemptively administered to reduce pain, swelling, and trismus following mandibular third molar surgeries. METHODS: A split-mouth randomized clinical trial was performed including 22 participants undergoing surgical removal of bilateral and symmetrically positioned third molars. A total of 44 teeth were allocated by simple randomization to either the test or nonintervention/control side. Oral dexamethasone 4 mg was administered on the test side an hour before the surgery. All of the participants were unaware of the medication studied, and only 1 surgeon, blinded to the medication intake, performed all of the procedures. Anti-inflammatory effect was evaluated using the clinical parameters of mouth opening, swelling, and rescue analgesic medication intake to control pain. The statistical analysis was blinded to the allocation groups, and a significance value P < .05 was adopted for all the tests. RESULTS: Dexamethasone reduced the mean of rescue analgesic medication intake by 5 times (P = .002). Facial swelling was lower on the test side by 72h postsurgery in comparison with the control side (P = .036). No significant difference in mouth opening was found between the groups. CONCLUSIONS: Preemptive use of oral dexamethasone 4 mg proved to be effective in controlling pain and reducing the need for rescue medication and had a beneficial effect in reducing swelling during a short postoperative period.


Asunto(s)
Tercer Molar , Diente Impactado , Antiinflamatorios/uso terapéutico , Dexametasona/uso terapéutico , Edema/tratamiento farmacológico , Edema/prevención & control , Humanos , Tercer Molar/cirugía , Dimensión del Dolor , Dolor Postoperatorio/tratamiento farmacológico , Dolor Postoperatorio/prevención & control , Extracción Dental , Trismo/tratamiento farmacológico , Trismo/etiología , Trismo/prevención & control
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