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1.
Laterality ; 29(1): 97-116, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-37962492

RESUMEN

Whereas a rightward bump is more likely than a leftward bump when walking through a doorway, investigations into potential similar asymmetries for drivers are limited. The research presented here aims to determine the influence of innate lateral spatial biases when driving. Data from the Strategic Highway Research Program Naturalistic Driving Study (SHRP 2 NDS) and a driving simulation were used to address our research questions. Data points from SHRP 2 were aggregated within relevant variables (e.g., left/right obstacles). In the simulation, participants drove in ways that were consistent with their everyday driving in urban and rural environments. Collision frequency, collision severity and average lateral lane position were analyzed with rightward biases throughout both analyzes. SHRP 2 data indicated greater likelihoods of collisions when vehicles crossed the right line/edge of the road and when making a right turn. There were more collisions with obstacles on the right side, which were also more severe, and greater rightward lane deviations in the driving simulation, contrasted with more severe collisions on the left side in SHRP 2 data, possibly because of the presence of traffic. These findings suggest that previously observed rightward biases in distant space when walking are also present when driving.


Asunto(s)
Conducción de Automóvil , Humanos , Lateralidad Funcional , Sesgo , Caminata
2.
Chembiochem ; 24(19): e202300406, 2023 Oct 04.
Artículo en Inglés | MEDLINE | ID: mdl-37382991

RESUMEN

Current treatment for Chagas' disease is based on two drugs, Nifurtimox and Benznidazol, which have limitations that reduce the effectiveness and continuity of treatment. Thus, there is an urgent need to develop new, safe and effective drugs. In previous work, two new metal-based compounds with trypanocidal activity, Pd-dppf-mpo and Pt-dppf-mpo, were fully characterized. To unravel the mechanism of action of these two analogous metal-based drugs, high-throughput omics studies were performed. A multimodal mechanism of action was postulated with several candidates as molecular targets. In this work, we validated the ergosterol biosynthesis pathway as a target for these compounds through the determination of sterol levels by HPLC in treated parasites. To understand the molecular level at which these compounds participate, two enzymes that met eligibility criteria at different levels were selected for further studies: phosphomevalonate kinase (PMK) and lanosterol 14-α demethylase (CYP51). Molecular docking processes were carried out to search for potential sites of interaction for both enzymes. To validate these candidates, a gain-of-function strategy was used through the generation of overexpressing PMK and CYP51 parasites. Results here presented confirm that the mechanism of action of Pd-dppf-mpo and Pt-dppf-mpo compounds involves the inhibition of both enzymes.

3.
Sensors (Basel) ; 23(9)2023 Apr 28.
Artículo en Inglés | MEDLINE | ID: mdl-37177563

RESUMEN

Modern wireless communication systems rely heavily on multiple antennas and their corresponding signal processing to achieve optimal performance. As 5G and 6G networks emerge, beamforming and beam management become increasingly complex due to factors such as user mobility, a higher number of antennas, and the adoption of elevated frequencies. Artificial intelligence, specifically machine learning, offers a valuable solution to mitigate this complexity and minimize the overhead associated with beam management and selection, all while maintaining system performance. Despite growing interest in AI-assisted beamforming, beam management, and selection, a comprehensive collection of datasets and benchmarks remains scarce. Furthermore, identifying the most-suitable algorithm for a given scenario remains an open question. This article aimed to provide an exhaustive survey of the subject, highlighting unresolved issues and potential directions for future developments. The discussion encompasses the architectural and signal processing aspects of contemporary beamforming, beam management, and selection. In addition, the article examines various communication challenges and their respective solutions, considering approaches such as centralized/decentralized, supervised/unsupervised, semi-supervised, active, federated, and reinforcement learning.

4.
Nano Lett ; 22(1): 179-187, 2022 01 12.
Artículo en Inglés | MEDLINE | ID: mdl-34918516

RESUMEN

We used single-molecule AFM force spectroscopy (AFM-SMFS) in combination with click chemistry to mechanically dissociate anticalin, a non-antibody protein binding scaffold, from its target (CTLA-4), by pulling from eight different anchor residues. We found that pulling on the anticalin from residue 60 or 87 resulted in significantly higher rupture forces and a decrease in koff by 2-3 orders of magnitude over a force range of 50-200 pN. Five of the six internal anchor points gave rise to complexes significantly more stable than N- or C-terminal anchor points, rupturing at up to 250 pN at loading rates of 0.1-10 nN s-1. Anisotropic network modeling and molecular dynamics simulations helped to explain the geometric dependency of mechanostability. These results demonstrate that optimization of attachment residue position on therapeutic binding scaffolds can provide large improvements in binding strength, allowing for mechanical affinity maturation under shear stress without mutation of binding interface residues.


Asunto(s)
Simulación de Dinámica Molecular , Proteínas , Antígeno CTLA-4 , Microscopía de Fuerza Atómica/métodos , Unión Proteica , Proteínas/química
5.
Appl Soft Comput ; 134: 110014, 2023 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-36687763

RESUMEN

Coronavirus Disease-2019 (COVID-19) causes Severe Acute Respiratory Syndrome-Corona Virus-2 (SARS-CoV-2) and has opened several challenges for research concerning diagnosis and treatment. Chest X-rays and computed tomography (CT) scans are effective and fast alternatives to detect and assess the damage that COVID causes to the lungs at different stages of the disease. Although the CT scan is an accurate exam, the chest X-ray is still helpful due to the cheaper, faster, lower radiation exposure, and is available in low-incoming countries. Computer-aided diagnostic systems based on Artificial Intelligence (AI) and computer vision are an alternative to extract features from X-ray images, providing an accurate COVID-19 diagnosis. However, specialized and expensive computational resources come across as challenging. Also, it needs to be better understood how low-cost devices and smartphones can hold AI models to predict diseases timely. Even using deep learning to support image-based medical diagnosis, challenges still need to be addressed once the known techniques use centralized intelligence on high-performance servers, making it difficult to embed these models in low-cost devices. This paper sheds light on these questions by proposing the Artificial Intelligence as a Service Architecture (AIaaS), a hybrid AI support operation, both centralized and distributed, with the purpose of enabling the embedding of already-trained models on low-cost devices or smartphones. We demonstrated the suitability of our architecture through a case study of COVID-19 diagnosis using a low-cost device. Among the main findings of this paper, we point out the performance evaluation of low-cost devices to handle COVID-19 predicting tasks timely and accurately and the quantitative performance evaluation of CNN models embodiment on low-cost devices.

6.
AIDS Res Ther ; 19(1): 12, 2022 02 24.
Artículo en Inglés | MEDLINE | ID: mdl-35209929

RESUMEN

BACKGROUND: Pre-Exposure Prophylaxis (PrEP) has demonstrated efficacy in the reduction of sexually transmitted HIV infections. The prolonged use of tenofovir disoproxil fumarate (TDF) and emtricitabine (FTC) co-formulation (TDF/FTC), however, may result in augmented risk of renal toxicity. We aimed to evaluate changes in the estimated Glomerular Filtration Rate (eGFR) in a real-world population setting of participants enrolled in PrEP Brazil, a 48-week prospective, open-label, demonstration study to assess the feasibility of daily oral TDF/FTC used by men who have sex with men and transgender women at high-risk of HIV infection, all over 18 years old. METHODS: Kidney function was assessed by serial measurement of serum creatinine and eGFR with the Modification of Diet in Renal Disease Study (MDRD) formula on weeks 4, 12, 24, 36 and 48. Adherence to PrEP was assessed by dosing TDF concentration in dried blood spots at weeks 4 and 48, measured by liquid chromatography-mass spectrometry or mass spectrometry. RESULTS: Of 392 participants completing the 48-week follow-up protocol with TDF blood detectable levels and eGFR measures, 43.1% were young adults, of Caucasian ethnic background (57.9%), with BMI below 30 kg/m2, without arterial hypertension. At screening, median eGFR was 93.0 mL/min/1.73 m2. At week 4 follow-up, 90 (23% of the study population) participants presented reductions in eGFR greater than 10 mL/min/1.73 m2 as compared to baseline eGFR, some as large as 59 mL/min/1.73 m2, but with no clinical outcomes (adverse events and renal adverse events) severe enough to demand TDF/FTC discontinuation. A negative relationship was observed between TDF blood levels and eGFR at weeks 4 (r = - 0.005; p < 0.01) and 48 (r = - 0.006; p < 0.01). CONCLUSIONS: These results suggest that the renal function profile in individuals on TDF/FTC may be assessed on week 4 and then only annually, allowing a more flexible medical follow-up in primary care centers.


Asunto(s)
Fármacos Anti-VIH , Infecciones por VIH , Profilaxis Pre-Exposición , Minorías Sexuales y de Género , Adolescente , Fármacos Anti-VIH/efectos adversos , Brasil/epidemiología , Emtricitabina/efectos adversos , Emtricitabina/uso terapéutico , Femenino , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/prevención & control , Homosexualidad Masculina , Humanos , Riñón , Masculino , Profilaxis Pre-Exposición/métodos , Estudios Prospectivos , Inhibidores de la Transcriptasa Inversa/uso terapéutico , Tenofovir/efectos adversos , Adulto Joven
7.
Int J Mol Sci ; 23(15)2022 Jul 31.
Artículo en Inglés | MEDLINE | ID: mdl-35955639

RESUMEN

The self-assembly process of ß-D-glucose oligomers on the surface of cellulose Iß microfibril involves crystallization, and this process is analyzed herein, in terms of the length and flexibility of the oligomer chain, by means of molecular dynamics (MD) simulations. The characterization of this process involves the structural relaxation of the oligomer, the recognition of the cellulose I microfibril, and the formation of several hydrogen bonds (HBs). This process is monitored on the basis of the changes in non-bonded energies and the interaction with hydrophilic and hydrophobic crystal faces. The oligomer length is considered a parameter for capturing insight into the energy landscape and its stability in the bound form with the cellulose I microfibril. We notice that the oligomer-microfibril complexes are more stable by increasing the number of hydrogen bond interactions, which is consistent with a gain in electrostatic energy. Our studies highlight the interaction with hydrophilic crystal planes on the microfibril and the acceptor role of the flexible oligomers in HB formation. In addition, we study by MD simulation the interaction between a protofibril and the cellulose I microfibril in solution. In this case, the main interaction consists of the formation of hydrogen bonds between hydrophilic faces, and those HBs involve donor groups in the protofibril.


Asunto(s)
Celulosa , Microfibrillas , Celulosa/química , Enlace de Hidrógeno , Interacciones Hidrofóbicas e Hidrofílicas , Simulación de Dinámica Molecular
8.
J Stroke Cerebrovasc Dis ; 31(5): 106405, 2022 May.
Artículo en Inglés | MEDLINE | ID: mdl-35276476

RESUMEN

OBJECTIVES: We aimed to evaluate the relationship between social distancing, stroke admissions and stroke mortality during the COVID-19 pandemic, while accounting for the rate of COVID-19 admissions. METHODS: We performed a longitudinal analysis of a multicenter, prospective, hospital-based registry of intensive care units from 19 hospitals from Brazil, comprising a 14-month period of the COVID-19 pandemic. We investigated whether the daily rate of admissions (DRAstroke) and daily mortality rate for stroke were associated with the social distancing index (SDI), taking into account the daily rate of admissions for COVID-19 (DRACOVID) in univariate and multivariate regression models. We also compared the clinical characteristics of patients with stroke admitted before and during the pandemic. RESULTS: We found that DRAstroke decreased significantly in association with a strong rise in the SDI during the early months of the pandemic. However, in the latter period of the pandemic, only minor changes were observed in the SDI, and still, DRAstroke was inversely associated with the DRACOVID. Throughout the pandemic, higher SDI and DRACOVID were associated with higher in-hospital mortality for stroke. CONCLUSIONS: The severity of surges of the COVID-19 pandemic were independently and persistently associated with declines in stroke admissions, even during periods when social distancing policies were not intensified.


Asunto(s)
COVID-19 , Accidente Cerebrovascular , Humanos , Estudios Longitudinales , Pandemias , Distanciamiento Físico , Estudios Prospectivos , Accidente Cerebrovascular/diagnóstico , Accidente Cerebrovascular/epidemiología , Accidente Cerebrovascular/terapia
9.
Molecules ; 27(3)2022 Feb 01.
Artículo en Inglés | MEDLINE | ID: mdl-35164241

RESUMEN

High resolution data from all-atom molecular simulations is used to parameterize a Martini 3 coarse-grained (CG) model of cellulose I allomorphs and cellulose type-II fibrils. In this case, elementary molecules are represented by four effective beads centred in the positions of O2, O3, C6, and O6 atoms in the D-glucose cellulose subunit. Non-bonded interactions between CG beads are tuned according to a low statistical criterion of structural deviation using the Martini 3 type of interactions and are capable of being indistinguishable for all studied cases. To maintain the crystalline structure of each single cellulose chain in the microfibrils, elastic potentials are employed to retain the ribbon-like structure in each chain. We find that our model is capable of describing different fibril-twist angles associated with each type of cellulose fibril in close agreement with atomistic simulation. Furthermore, our CG model poses a very small deviation from the native-like structure, making it appropriate to capture large conformational changes such as those that occur during the self-assembly process. We expect to provide a computational model suitable for several new applications such as cellulose self-assembly in different aqueous solutions and the thermal treatment of fibrils of great importance in bioindustrial applications.

10.
J Clin Densitom ; 22(2): 279-286, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-29661687

RESUMEN

The historical concept that obesity protects against bone fractures has been questioned. Weight loss appears to reduce bone mineral density (BMD); however, the results in young adults are inconsistent, and data on the effects of weight loss on bone microstructure are limited. This study aimed to evaluate the impact of weight loss using an intragastric balloon (IGB) on bone density and microstructure. Forty obese patients with metabolic syndrome (mean age 35.1 ± 7.3 yr) used an IGB continuously for 6 mo. Laboratory tests, areal BMD, and body composition measurements via dual-energy X-ray absorptiometry, and volumetric BMD and bone microstructure measurements via high-resolution peripheral quantitative computed tomography were conducted before IGB placement and after IGB removal. The mean weight loss was 11.5%. After 6 mo, there were significant increases in vitamin D and carboxyterminal telopeptide of type 1 collagen levels. After IGB use, areal BMD increased in the spine but decreased in the total femur and the 33% radius. Cortical BMD increased in the distal radius but tended to decrease in the distal tibia. The observed trabecular bone loss in the distal tibia contributed to the decline in the total volumetric BMD at this site. There was a negative correlation between the changes in leptin levels and the measures of trabecular quality in the tibia on high-resolutionperipheral quantitative computed tomography. Weight loss may negatively impact bone microstructure in young patients, especially for weight-bearing bones, in which obesity has a more prominent effect.


Asunto(s)
Densidad Ósea , Hueso Esponjoso/diagnóstico por imagen , Hueso Cortical/diagnóstico por imagen , Balón Gástrico , Obesidad/terapia , Pérdida de Peso , Absorciometría de Fotón , Adulto , Colágeno Tipo I/sangre , Femenino , Fémur/diagnóstico por imagen , Cuello Femoral/diagnóstico por imagen , Humanos , Leptina/sangre , Vértebras Lumbares/diagnóstico por imagen , Masculino , Síndrome Metabólico/sangre , Síndrome Metabólico/complicaciones , Obesidad/sangre , Obesidad/complicaciones , Obesidad/diagnóstico por imagen , Péptidos/sangre , Radio (Anatomía)/diagnóstico por imagen , Tibia/diagnóstico por imagen , Tomografía Computarizada por Rayos X , Resultado del Tratamiento , Vitamina D/análogos & derivados , Vitamina D/sangre
11.
J Dairy Sci ; 102(4): 2966-2972, 2019 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-30712936

RESUMEN

Sodium chloride reduction in foods is a significant focus of the dairy industry; however, it can interfere with dairy product quality. Thus, researchers have carried out studies on alternatives to maintain dairy product safety when presenting reduced NaCl content, such as natural antimicrobial addition. Caryocar brasiliense (pequi) is a fruit with high phenolic compound concentrations in the pulp and peel and known antioxidant and antimicrobial properties. This study aimed to define the optimum stage for pequi waste extract addition during cheese manufacturing in order to maintain and prolong the shelf life of reduced-sodium goat Minas Frescal cheese. Four different goat Minas Frescal cheese treatments were carried out: control cheese (without extract; CC), pequi extract addition to milk (CM), pequi extract addition to mass (CS), and cheese immersion in pequi extract (CIE). The treatments were subjected to microbiological (Staphylococcus spp., Escherichia coli, Enterobacteriaceae, coliforms and fecal coliforms, Lactococcus spp., and lactic acid bacteria counts), textural (hardness and consistency), and instrumental color (luminosity, yellow intensity, red intensity, chroma, hue angle, and total color change) analyses. No Enterobacteriaceae, Staphylococcus spp., E. coli, or coliforms and fecal coliforms were detected during storage for any of the assessed samples, including CC. Regarding texture, all samples presented a trend for decreasing rigidity during storage. In addition, lower luminosity values were also observed in cheeses produced with added pequi extract (CM, CS, and CIE) when compared with CC. All cheeses produced with added pequi were stable regarding all evaluated parameters; however, pequi extract addition to milk (CM) was shown to be more efficient, leading to higher textural parameters and better microbiological quality during storage. Thus, the CM treatment is the most recommended for pequi waste extract addition during Minas Frescal cheese manufacture.


Asunto(s)
Antiinfecciosos/farmacología , Queso/microbiología , Malpighiales/química , Leche/microbiología , Extractos Vegetales/farmacología , Animales , Industria Lechera , Enterobacteriaceae/efectos de los fármacos , Escherichia coli , Cabras , Lactobacillales , Lactococcus/efectos de los fármacos , Leche/química , Cloruro de Sodio/análisis , Staphylococcus/efectos de los fármacos
12.
Int Braz J Urol ; 44(2): 384-389, 2018.
Artículo en Inglés | MEDLINE | ID: mdl-29039895

RESUMEN

INTRODUCTION: The appropriate closure of the urinary bladder is important to many urologic procedures to avoid the formation of fistulas and strictures by excessive fibrosis. This paper presents the alterations in the bladder healing process of rats after the topical use of Copaiba oil (Copaifera reticulata). MATERIAL AND METHODS: Ten male Wistar rats were used and randomly divided into two groups: Control group (CG): injected 1ml/kg of saline solution on the suture line; and Copaiba group (CpG): 0.63ml/kg of copaiba oil applied to the suture line. Euthanasia was performed on the seventh day after surgery. The criteria observed were adherences formation, histopathological modifications and stereology for collagen. RESULTS: Both groups showed adhesions to the bladder, with no statistically significant difference (p=0.1481). The microscopic evaluation revealed a trend to more severe acute inflammation process on the CpG, but there was statistical difference only in the giant cells reaction (p=0.0472) and vascular proliferation (p=0.0472). The stereology showed no difference. CONCLUSION: The copaiba oil modified the healing process, improving the quantity of giant cells and vascular proliferation, but not interfered in the collagen physiology.


Asunto(s)
Fabaceae/química , Aceites de Plantas/farmacología , Vejiga Urinaria/efectos de los fármacos , Cicatrización de Heridas/efectos de los fármacos , Administración Tópica , Animales , Modelos Animales de Enfermedad , Masculino , Aceites de Plantas/administración & dosificación , Distribución Aleatoria , Ratas , Ratas Wistar , Vejiga Urinaria/patología , Vejiga Urinaria/cirugía
13.
Health Qual Life Outcomes ; 15(1): 211, 2017 Oct 24.
Artículo en Inglés | MEDLINE | ID: mdl-29065923

RESUMEN

BACKGROUND: Obesity is a worldwide public health issue with a negative impact on quality of life. Different weight loss interventions have demonstrated improvements in quality of life. The aim of this study was to investigate the effect of 6 months of treatment with an intragastric balloon (IGB) on health-related quality of life (HRQOL) and its relation to changes in body fat in obese individuals with metabolic syndrome (MS). METHODS: Fifty obese patients with MS aged 18-50 were selected for treatment with IGB for 6 months. Body fat was assessed with anthropometric measures and dual-energy X-ray absorptiometry (DXA) at baseline and after removal of the IGB. HRQOL was evaluated with the short form of the World Health Organization Quality of Life (WHOQOL-BREF) at baseline and soon after removal of the IGB. RESULTS: Thirty-nine patients completed the study. After 6 months, there was a significant improvement in quality of life (p = 0.0009) and health (p < 0.0001) perceptions, and in the Physical (p = 0.001), Psychological (p = 0.031), and Environmental domains (p = 0.0071). Anthropometric measures and total fat determined by DXA were directly and significantly related to an improvement in general aspects of quality of life. The decrease in the percentage of total fat was the parameter that better correlated with improvements in quality of life perception after regression (p = 0.032). CONCLUSIONS: In obese individuals with MS, weight loss parameters were associated with short-term improvements in HRQOL after 6 months of treatment with IGB. However, only total fat was independently related to HRQOL perception. TRIAL REGISTRATION: ClinicalTrials.gov NCT01598233 .


Asunto(s)
Tejido Adiposo , Balón Gástrico , Síndrome Metabólico/psicología , Obesidad/psicología , Calidad de Vida , Pérdida de Peso , Adulto , Anciano , Índice de Masa Corporal , Femenino , Humanos , Masculino , Síndrome Metabólico/complicaciones , Persona de Mediana Edad , Obesidad/complicaciones
14.
BMC Infect Dis ; 16: 376, 2016 Aug 08.
Artículo en Inglés | MEDLINE | ID: mdl-27503230

RESUMEN

BACKGROUND: Antiretroviral therapy (ART) agents potentially associated with adverse metabolic profiles are commonly used in low- and middle-income countries. We assessed risk factors for cardiovascular disease (CVD)-related morbidity and mortality in a cohort of HIV-infected, ART-treated adults in Rio de Janeiro, Brazil. METHODS: Hospital records and mortality data between 2000-2010 were examined for incident CVD-related ICD-10 and Coding of Death in HIV diagnoses among adults ≥18 years old on ART, enrolled in an observational cohort. Poisson regression models assessed associations between demographic and clinical characteristics and ART agent or class on CVD event risk. RESULTS: Of 2960 eligible persons, 109 had a CVD event (89 hospitalizations, 20 deaths). Participants were 65 % male, 54 % white, and had median age of 37 and 4.6 years on ART. The median nadir CD4(+) T lymphocyte count was 149 cells/mm(3). The virologic suppression rate at the end of study follow-up was 60 %. In multivariable models, detectable HIV-1 RNA prior to the event, prior CVD, less time on ART, age ≥40 at study baseline, nadir CD4(+) T lymphocyte count ≤50 cells/mm(3), non-white race, male gender, and a history of hypertension were significantly associated with CVD event incidence (p < 0.05), in order of decreasing strength. In multivariate models, cumulative use of tenofovir, zidovudine, efavirenz and ritonavir-boosted atazanavir, darunavir and/or lopinavir were associated with decreased CVD event risk. Recent tenofovir and boosted atazanavir use were associated with decreased risk, while recent stavudine, nevirapine and unboosted nelfinavir and/or indinavir use were associated with increased CVD event risk. CONCLUSIONS: Virologic suppression and preservation of CD4(+) T-lymphocyte counts were as important as traditional CVD risk factor burden in determining incident CVD event risk, emphasizing the overall benefit of ART on CVD risk and the need for metabolically-neutral first- and second-line ART in resource-limited settings.


Asunto(s)
Fármacos Anti-VIH/uso terapéutico , Enfermedades Cardiovasculares/epidemiología , Etnicidad/estadística & datos numéricos , Infecciones por VIH/tratamiento farmacológico , Adulto , Factores de Edad , Población Negra , Brasil/epidemiología , Recuento de Linfocito CD4 , Enfermedades Cardiovasculares/mortalidad , Estudios de Cohortes , Femenino , Infecciones por VIH/sangre , Infecciones por VIH/epidemiología , VIH-1/genética , Humanos , Hipertensión/epidemiología , Incidencia , Masculino , Persona de Mediana Edad , Análisis Multivariante , ARN Viral/sangre , Análisis de Regresión , Estudios Retrospectivos , Factores de Riesgo , Factores Sexuales , Factores de Tiempo , Carga Viral , Población Blanca
15.
Antimicrob Agents Chemother ; 58(6): 3021-8, 2014 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-24614380

RESUMEN

Miltefosine (MT) is a membrane-active alkylphospholipid licensed for the topical treatment of breast cancer skin metastases and the oral treatment of leishmaniasis, although its mechanism of action remains unclear. Electron paramagnetic resonance (EPR) spectroscopy of a spin-labeled lipid and a thiol-specific spin label in the plasma membrane of Leishmania promastigotes showed that MT causes dramatic increases in membrane dynamics. Although these alterations can be detected using a spin-labeled lipid, our experimental results indicated that MT interacts predominantly with the protein component of the membrane. Cell lysis was also detected by analyzing the supernatants of centrifuged samples for the presence of spin-labeled membrane fragments and cytoplasmic proteins. Using a method for the rapid incorporation of MT into the membrane, these effects were measured immediately after treatment under the same range of MT concentrations that cause cell growth inhibition. Cytotoxicity, estimated via microscopic counting of living and dead cells, indicated ∼70% cell death at the concentration of MT at which EPR spectroscopy detected a significant change in membrane dynamics. After this initial impact on the number of viable parasites, the processes of cell death and growth continued during the first 4 h of incubation. The EPR spectra of spin-labeled membrane-bound proteins were consistent with more expanded and solvent-exposed protein conformations, suggesting a detergent-like action. Thus, MT may form micelle-like structures around polypeptide chains, and proteins with a higher hydrophobicity may induce the penetration of hydrophilic groups of MT into the membrane, causing its rupture.


Asunto(s)
Antineoplásicos/farmacología , Leishmania mexicana/efectos de los fármacos , Lípidos de la Membrana/metabolismo , Proteínas de la Membrana/metabolismo , Fosforilcolina/análogos & derivados , Membrana Celular/metabolismo , Supervivencia Celular/efectos de los fármacos , Espectroscopía de Resonancia por Spin del Electrón , Humanos , Interacciones Hidrofóbicas e Hidrofílicas , Leishmania mexicana/metabolismo , Micelas , Simulación de Dinámica Molecular , Fosforilcolina/química , Fosforilcolina/farmacología , Conformación Proteica , Marcadores de Spin
16.
J Chem Phys ; 141(12): 124712, 2014 Sep 28.
Artículo en Inglés | MEDLINE | ID: mdl-25273466

RESUMEN

Based on a quantum chemical valence formalism that allows the rigorous construction of best-localized molecular orbitals on specific parts of an extended system, we examined the separability of individual components of model systems relevant to the description of electron transport in molecular devices. We started by examining how to construct the maximally localized electronic density at the tip of a realistic model of a gold electrode. By varying the number of gold atoms included in the local region where to project the total electronic density, we quantitatively assess how many molecular orbitals are entirely localized in that region. We then considered a 1,4-benzene-di-thiol molecule connected to two model gold electrodes and examined how to localize the electronic density of the total system in the extended molecule, a fractional entity comprising the organic molecule plus an increasing number of the closest metal atoms. We were able to identify in a rigorous manner the existence of three physically different electronic populations, each one corresponding to a distinct set of molecular orbitals. First, there are those entirely localized in the extended molecule, then there is a second group of those completely distributed in the gold atoms external to that region, and, finally, there are those delocalized over the entire system. This latter group can be associated to the shared electronic population between the extended molecule and the rest of the system. We suggest that the treatment here presented could be useful in the theoretical analysis of the electronic transport in nanodevices whenever the use of localized molecular states are required by the physics of the specific problem, such as in cases of weak coupling and super-exchange limits.

17.
Sci Rep ; 14(1): 14067, 2024 Jun 18.
Artículo en Inglés | MEDLINE | ID: mdl-38890330

RESUMEN

Prioritizing watershed management interventions relies on delineating homogeneous precipitation regions. In this study, we identify these regions in the Brazilian Legal Amazon based on the magnitude of Sen's Slope trends using annual precipitation data from September to August, employing the Google Earth Engine platform. Utilizing the silhouette method, we determine four distinct clusters representing zones of homogeneous precipitation patterns. Cluster 0 exhibits a significant median increase in precipitation of 3.20 mm year-1 over the period from 1981 to 2020. Cluster 1 shows a notable increase of 8.13 mm year-1, while Clusters 2 and 3 demonstrate reductions in precipitation of - 1.61 mm year-1 and - 3.87 mm year-1, respectively, all statistically significant. Notably, the region known as the arc of deforestation falls within Cluster 2, indicating a concerning trend of reduced precipitation. Additionally, our analysis reveals significant correlations between Sea Surface Temperature (SST) in various oceanic regions and precipitation patterns over the Brazilian Legal Amazon. Particularly noteworthy is the strong positive correlation with SST in the South Atlantic, while negative correlations are observed with SST in the South Pacific and North Atlantic. These findings provide valuable insights for enhancing climate adaptation strategies in the Brazilian Legal Amazon region.

18.
PLOS Glob Public Health ; 4(5): e0002576, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38722828

RESUMEN

INTRODUCTION: The outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) posed a significant public health challenge globally, with Brazil being no exception. Excess mortality during this period reached alarming levels. Cardiovascular diseases (CVD), Systemic Hypertension (HTN), and Diabetes Mellitus (DM) were associated with increased mortality. However, the specific impact of DM and HTN on mortality during the pandemic remains poorly understood. METHODS: This study analyzed mortality data from Brazil's mortality system, covering the period from 2015 to 2022. Data included all causes of death as listed on death certificates, categorized by International Classification of Diseases 10th edition (ICD-10) codes. Population data were obtained from the Brazilian Census. Mortality ratios (MRs) were calculated by comparing death rates in 2020, 2021, and 2022 to the average rates from 2015 to 2019. Adjusted MRs were calculated using Poisson models. RESULTS: Between 2015 and 2022, Brazil recorded a total of 11,423,288 deaths. Death rates remained relatively stable until 2019 but experienced a sharp increase in 2020 and 2021. In 2022, although a decrease was observed, it did not return to pre-pandemic levels. This trend persisted even when analyzing records mentioning DM, HTN, or CVD. Excluding death certificates mentioning COVID-19 codes, the trends still showed increases from 2020 through 2022, though less pronounced. CONCLUSION: This study highlights the persistent high mortality rates for DM and HTN in Brazil during the years 2020-2022, even after excluding deaths associated with COVID-19. These findings emphasize the need for continued attention to managing and preventing DM and HTN as part of public health strategies, both during and beyond the COVID-19 pandemic. There are complex interactions between these conditions and the pandemic's impact on mortality rates.

19.
Am J Cardiol ; 214: 157-166, 2024 Mar 01.
Artículo en Inglés | MEDLINE | ID: mdl-38160920

RESUMEN

Smoking is highly prevalent in people living with HIV/AIDS (PLHA), leading to detrimental effects in different tissues. We examined the effects of nicotine replacement therapy (NRT) on smoking cessation and vascular health. From December 2019 to October 2021, we prospectively enrolled PLHA who were actively smoking. The primary outcome was endothelial function measured by brachial artery flow-mediated dilatation (FMD). We evaluated the percent change in FMD compared to the baseline measure (Δ%FMD) to detect improvements among participants who quit smoking. To confirm the results, we used linear regression models to account for classical cardiovascular (CV) confounders. We included 117 participants with median age of 45.5 years (IQR= 36.4-54.8); 22 (20.4%) had hypertension, 9 (8.3%) had diabetes, almost half were smoking 20+ cigarettes/day (41.7%). After 12 weeks 30.76% participants quit smoking. Comparison of Δ%FMD change from baseline to week 12 showed that among participants adherent to therapy, there has been an increase in Δ%FMD when compared to those who relapsed (1.17% [0.29-2.98] vs -0.19% [-1.95-0.91], p<0.001). After adjustment for CV factors, multiple linear regression showed that Δ%FMD in participants who quit smoking presented a 2.54 mean increase in comparison to those who continued smoking (p=0.007). In conclusion, this study provides evidence that a strategy of NRT and counseling is modestly effective for smoking cessation in PLHA and improves vascular health in a short period of time. This reinforces the importance of the widespread anti-tobacco programs in HIV clinics and the expected impact lowering the incidence of future cardiovascular events.


Asunto(s)
Infecciones por VIH , Cese del Hábito de Fumar , Humanos , Adulto , Persona de Mediana Edad , Cese del Hábito de Fumar/métodos , Nicotina , Brasil/epidemiología , Dispositivos para Dejar de Fumar Tabaco , Infecciones por VIH/complicaciones , Infecciones por VIH/epidemiología
20.
Sci Rep ; 14(1): 14227, 2024 06 20.
Artículo en Inglés | MEDLINE | ID: mdl-38902311

RESUMEN

Agricultural production assessments are crucial for formulating strategies for closing yield gaps and enhancing production efficiencies. While in situ crop yield measurements can provide valuable and accurate information, such approaches are costly and lack scalability for large-scale assessments. Therefore, crop modeling and remote sensing (RS) technologies are essential for assessing crop conditions and predicting yields at larger scales. In this study, we combined RS and a crop growth model to assess phenology, evapotranspiration (ET), and yield dynamics at grid and sub-county scales in Kenya. We synthesized RS information from the Food and Agriculture Organization (FAO) Water Productivity Open-access portal (WaPOR) to retrieve sowing date information for driving the model simulations. The findings showed that grid-scale management information and progressive crop growth could be accurately derived, reducing the model output uncertainties. Performance assessment of the modeled phenology yielded satisfactory accuracies at the sub-county scale during two representative seasons. The agreement between the simulated ET and yield was improved with the combined RS-crop model approach relative to the crop model only, demonstrating the value of additional large-scale RS information. The proposed approach supports crop yield estimation in data-scarce environments and provides valuable insights for agricultural resource management enabling countermeasures, especially when shortages are perceived in advance, thus enhancing agricultural production.


Asunto(s)
Productos Agrícolas , Tecnología de Sensores Remotos , Zea mays , Kenia , Tecnología de Sensores Remotos/métodos , Zea mays/crecimiento & desarrollo , Productos Agrícolas/crecimiento & desarrollo , Producción de Cultivos/métodos , Agricultura/métodos , Modelos Teóricos , Estaciones del Año
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