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1.
Drugs Real World Outcomes ; 11(1): 149-165, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38381283

RESUMO

BACKGROUND: Patients with chronic thromboembolic pulmonary hypertension (CTEPH) in countries with limited resources have, to date, been poorly represented in registries. OBJECTIVE: This work assesses the epidemiology, diagnosis, hemodynamic and functional parameters, and treatment of CTEPH in Russia, Kazakhstan, Turkey, Lebanon, and Saudi Arabia. METHODS: A prospective, cohort, phase IV, observational registry with 3-year follow-up (n = 212) in patients aged ≥ 18 years diagnosed with CTEPH was created. Clinical, hemodynamic, and functional parameters were obtained at an initial visit, follow-up visits, and a final visit at the end of 3 years' observation or end of follow-up. Data were recorded on electronic case report forms. Parameters evaluated included 6-minute walking distance (6MWD), use of pulmonary endarterectomy (PEA), balloon pulmonary angioplasty (BPA), pulmonary hypertension (PH)-targeted therapy, and survival. All statistical analyses were exploratory and descriptive, and were performed in the overall population. RESULTS: The most common symptoms were typical of those expected for CTEPH. Almost 90% of patients underwent right heart catheterization at diagnosis or initial study visit. In total, 66 patients (31%) underwent PEA before the initial visit; 95 patients (45%) were considered operable, 115 (54%) were inoperable, and two (1%) had no operability data. Only 26 patients (12%) had been assessed for BPA at their initial visit. PH-targeted therapy was documented at diagnosis for 77 patients (36%), most commonly a phosphodiesterase type 5 inhibitor (23%). Use of PH-targeted therapy increased to 142 patients (67%) at the initial visit, remaining similar after 3 years. Use of riociguat increased from 6% of patients at diagnosis to 38% at 3 years. Between baseline and end of observation, results for patients with paired data showed an increase in 6MWD. Survival at the end of observation was 88%. CONCLUSIONS: These data highlight the current diagnosis and management of CTEPH in the participating countries. They show that early CTEPH diagnosis remains challenging, and use of off-label PH-targeted therapy is common. CLINICALTRIALS: gov: NCT02637050; registered December 2015.

2.
Int Ophthalmol ; 43(1): 141-146, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-35799075

RESUMO

PURPOSE: To evaluate the effects of Duloxetine on anterior segment parameters and intraocular pressure (IOP) in open angle eyes. METHODS: 38 eyes of 38 patients with fibromyalgia who had open or wide open angles according to the Shaffer classification. Anterior segment optic coherence tomography was performed before and after (month 3) Duloxetine treatment. IOP, central corneal thickness (CCT), corneal endothelial cell density (CECD) and anterior chamber depth (ACD) were also recorded and evaluated. RESULTS: No statistically significant difference was determined in IOP, CCT and CECD (p > 0.05). However, a statistically significant decrease was determined in both the temporal and nasal anterior chamber angle, angle opening distance, nasal trabecular-iris space area and ACD values between the baseline and month 3 (p < 0.001). DISCUSSION: We think that the short term use of Duloxetine does not lead to clinically significant changes despite their statistically significant effects on the anterior chamber parameters.


Assuntos
Glaucoma de Ângulo Fechado , Tomografia de Coerência Óptica , Humanos , Cloridrato de Duloxetina/uso terapêutico , Tomografia de Coerência Óptica/métodos , Câmara Anterior , Iris , Tonometria Ocular , Pressão Intraocular , Segmento Anterior do Olho/diagnóstico por imagem , Glaucoma de Ângulo Fechado/diagnóstico , Glaucoma de Ângulo Fechado/tratamento farmacológico , Gonioscopia
3.
Proc Natl Acad Sci U S A ; 119(42): e2213718119, 2022 10 18.
Artigo em Inglês | MEDLINE | ID: mdl-36215477

RESUMO

Transcription factors (TFs) play critical roles in hematopoiesis, and their aberrant expression can lead to various types of leukemia. The t(8;21) leukemogenic fusion protein AML1-ETO (AE) is the most common fusion protein in acute myeloid leukemia and can enhance hematopoietic stem cell renewal while blocking differentiation. A key question in understanding AE-mediated leukemia is what determines the choice of AE to activate self-renewal genes or repress differentiation genes. Toward the resolution of this problem, we earlier showed that AE resides in the stable AETFC complex and that its components colocalize on up- or down-regulated target genes and are essential for leukemogenesis. In the current study, using biochemical and genomic approaches, we show that AE-containing complexes are heterogeneous, and that assembly of the larger AETFC (containing AE, CBFß, HEB, E2A, LYL1, LMO2, and LDB1) requires LYL1. Furthermore, we provide strong evidence that the LYL1-containing AETFC preferentially binds to active enhancers and promotes AE-dependent gene activation. Moreover, we show that coactivator CARM1 interacts with AETFC and facilitates gene activation by AETFC. Collectively, this study describes a role of oncoprotein LYL1 in AETFC assembly and gene activation by recruiting CARM1 to chromatin for AML cell survival.


Assuntos
Leucemia Mieloide Aguda , Proteínas de Fusão Oncogênica , Fatores de Transcrição Hélice-Alça-Hélice Básicos/metabolismo , Proteínas Adaptadoras de Sinalização CARD , Cromatina , Subunidade alfa 2 de Fator de Ligação ao Core/genética , Subunidade alfa 2 de Fator de Ligação ao Core/metabolismo , Guanilato Ciclase , Humanos , Proteínas com Homeodomínio LIM/genética , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/metabolismo , Proteínas de Neoplasias/genética , Proteínas de Fusão Oncogênica/genética , Proteínas de Fusão Oncogênica/metabolismo , Proteína-Arginina N-Metiltransferases , Ativação Transcricional
4.
Sci Total Environ ; 852: 158382, 2022 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-36049692

RESUMO

This article presents the results of a long-term soil radon and meteorological parameter monitoring study in the fault zone at Mt. Beshtau, North Caucasus, which for more than 3 years. Strong seasonal variations in the radon levels with maxima during summer and minima during winter were recorded. The values of radon exhalation and soil radon concentration have a range of 0.025-25 Bq m 2 s -1 and 1-170 kBq m -3, respectively. In addition, measurements of the air radon concentration, and direction of air movement at the adits mouths of the former uranium mine on the same mountain were carried out. Seasonal radon variations, similar to those observed in fault zones, were recorded at the mouths of adits. It was established that radon anomalies are associated with the periodic release of mine air from the fractures and tunnels into the atmosphere. Above an altitude of 900 m a. s. l., an abnormal release of radon occurs in winter, when the mine air is warmer than the surrounding atmosphere. At the altitudes below 900 m the cold radon rich air blows from the adit mouths in summer. During mine air discharge, radon concentrations in the open atmosphere locally around the adit mouth reach 600,000 Bq m-3, averaging 50,000-250,000 Bq m-3. The temporal pattern of radon fluctuations in fault zones and at the adit mouths is similar. A very close correlation between radon levels and atmospheric air temperature was observed both in the fault zone and at the adits mouths. It indicates that radon release in both cases are caused by a single mechanism. This mechanism probably is the atmospheric air circulation in shallow permeable zones due to the temperature difference between the inside mountain and ambient atmosphere.


Assuntos
Poluentes Radioativos do Ar , Monitoramento de Radiação , Radônio , Urânio , Radônio/análise , Poluentes Radioativos do Ar/análise , Solo
5.
ACS Sens ; 7(7): 2037-2048, 2022 07 22.
Artigo em Inglês | MEDLINE | ID: mdl-35820167

RESUMO

Wearable and wireless monitoring of biomarkers such as lactate in sweat can provide a deeper understanding of a subject's metabolic stressors, cardiovascular health, and physiological response to exercise. However, the state-of-the-art wearable and wireless electrochemical systems rely on active sweat released either via high-exertion exercise, electrical stimulation (such as iontophoresis requiring electrical power), or chemical stimulation (such as by delivering pilocarpine or carbachol inside skin), to extract sweat under low-perspiring conditions such as at rest. Here, we present a continuous sweat lactate monitoring platform combining a hydrogel for osmotic sweat extraction, with a paper microfluidic channel for facilitating sweat transport and management, a screen-printed electrochemical lactate sensor, and a custom-built wireless wearable potentiostat system. Osmosis enables zero-electrical power sweat extraction at rest, while continuous evaporation at the end of a paper channel allows long-term sensing from fresh sweat. The positioning of the lactate sensors provides near-instantaneous sensing at low sweat volume, and the custom-designed potentiostat supports continuous monitoring with ultra-low power consumption. For a proof of concept, the prototype system was evaluated for continuous measurement of sweat lactate across a range of physiological activities with changing lactate concentrations and sweat rates: for 2 h at the resting state, 1 h during medium-intensity exercise, and 30 min during high-intensity exercise. Overall, this wearable system holds the potential of providing comprehensive and long-term continuous analysis of sweat lactate trends in the human body during rest and under exercising conditions.


Assuntos
Suor , Dispositivos Eletrônicos Vestíveis , Humanos , Ácido Láctico/análise , Monitorização Fisiológica , Osmose , Suor/química
6.
Work ; 71(3): 625-639, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-34366305

RESUMO

BACKGROUND: Population aging, caused by an increase in life expectancy and decrease in fertility rates, has created changes and challenges in various spheres, including the labor market. Though health deteriorates with age, more and more older adults choose to stay in the labor force and work into late life. OBJECTIVE: Understanding the effects of various work conditions on the health of older workers is crucial for designing policies and interventions to ensure healthy late life and maintain a productive workforce. To contribute to this endeavor, this study investigates the relationship between long working hours (LWH) and mortality among older populations. METHODS: The study uses the Cox proportional hazards regression model to investigate data from the Health and Retirement Survey (HRS) between the years 1992-2016, a longitudinal nationally representative dataset from the United States. RESULTS: The results indicate that working 50 hours or more per week is not associated with an increased risk of mortality, for the full sample (1.45 [95% CI: 0.86, 2.45]), for both genders (females 0.51 [95% CI: 0.06, 4.28], males 1.45 [95% CI: 0.81, 2.61]), and for immigrants (female immigrants 0.55 [95% CI: 0.06, 4.75], male immigrants 1.44 [95% CI: 0.79, 2.62]). CONCLUSIONS: This analysis confirms and extends the findings of earlier studies by taking into consideration the potential impact of many demographic, socioeconomic, work-related and health-related factors.


Assuntos
Emprego , Aposentadoria , Idoso , Envelhecimento , Feminino , Nível de Saúde , Humanos , Masculino , Ocupações , Estados Unidos/epidemiologia
7.
Annu Int Conf IEEE Eng Med Biol Soc ; 2021: 6863-6866, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34892683

RESUMO

Operating at low sweat rates, such as those experienced by humans at rest, is still an unmet need for state-of-the-art wearable sweat harvesting and testing devices for lactate. Here, we report the on-skin performance of a non-invasive wearable sweat sampling patch that can harvest sweat at rest, during exercise, and post-exercise. The patch simultaneously uses osmosis and evaporation for long-term (several hours) sampling of sweat. Osmotic sweat withdrawal is achieved by skin-interfacing a hydrogel containing a concentrated solute. The gel interfaces with a paper strip that transports the fluid via wicking and evaporation. Proof of concept results show that the patch was able to sample sweat during resting and post-exercise conditions, where the lactate concentration was successfully quantified. The patch detected the increase in sweat lactate levels during medium level exercise. Blood lactate remained invariant with exercise as expected. We also developed a continuous sensing version of the patch by including enzymatic electrochemical sensors. Such a battery-free, passive, wearable sweat sampling patch can potentially provide useful information about the human metabolic activity.


Assuntos
Suor , Dispositivos Eletrônicos Vestíveis , Humanos , Hidrogéis , Ácido Láctico , Sudorese
8.
Proc Natl Acad Sci U S A ; 118(27)2021 07 06.
Artigo em Inglês | MEDLINE | ID: mdl-34187895

RESUMO

DOT1L, the only H3K79 methyltransferase in human cells and a homolog of the yeast Dot1, normally forms a complex with AF10, AF17, and ENL or AF9, is dysregulated in most cases of mixed-lineage leukemia (MLLr), and has been believed to regulate transcriptional elongation on the basis of its colocalization with RNA polymerase II (Pol II), the sharing of subunits (AF9 and ENL) between the DOT1L and super elongation complexes, and the distribution of H3K79 methylation on both promoters and transcribed regions of active genes. Here we show that DOT1L depletion in erythroleukemic cells reduces its global occupancy without affecting the traveling ratio or the elongation rate (assessed by 4sUDRB-seq) of Pol II, suggesting that DOT1L does not play a major role in elongation in these cells. In contrast, analyses of transcription initiation factor binding reveal that DOT1L and ENL depletions each result in reduced TATA binding protein (TBP) occupancies on thousands of genes. More importantly, DOT1L and ENL depletions concomitantly reduce TBP and Pol II occupancies on a significant fraction of direct (DOT1L-bound) target genes, indicating a role for the DOT1L complex in transcription initiation. Mechanistically, proteomic and biochemical studies suggest that the DOT1L complex may regulate transcriptional initiation by facilitating the recruitment or stabilization of transcription factor IID, likely in a monoubiquitinated H2B (H2Bub1)-enhanced manner. Additional studies show that DOT1L enhances H2Bub1 levels by limiting recruitment of the Spt-Ada-Gcn5-acetyltransferase (SAGA) complex. These results advance our understanding of roles of the DOT1L complex in transcriptional regulation and have important implications for MLLr leukemias.


Assuntos
Histona-Lisina N-Metiltransferase/metabolismo , Leucemia Eritroblástica Aguda/genética , Iniciação da Transcrição Genética , Linhagem Celular Tumoral , Cromatina/metabolismo , Regulação Leucêmica da Expressão Gênica , Histonas/metabolismo , Humanos , Ligação Proteica , RNA Polimerase II/metabolismo , Elongação da Transcrição Genética , Fator de Transcrição TFIID/metabolismo , Fatores de Elongação da Transcrição/metabolismo , Ubiquitinação
9.
Biosens Bioelectron ; 184: 113249, 2021 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-33895689

RESUMO

Advances in materials, bio-recognition elements, transducers, and microfabrication techniques, as well as progress in electronics, signal processing, and wireless communication have generated a new class of skin-interfaced wearable health monitoring systems for applications in personalized medicine and digital health. In comparison to conventional medical devices, these wearable systems are at the cusp of initiating a new era of longitudinal and noninvasive sensing for the prevention, detection, diagnosis, and treatment of diseases at the molecular level. Herein, we provide a review of recent developments in wearable biochemical and biophysical systems. We survey the sweat sampling and collection methods for biochemical systems, followed by an assessment of biochemical and biophysical sensors deployed in current wearable systems with an emphasis on their hardware specifications. Specifically, we address how sweat collection and sample handling platforms may be a rate limiting technology to realizing the clinical translation of wearable health monitoring systems; moreover, we highlight the importance of achieving both longitudinal sensing and assessment of intrapersonal variation in sweat-blood correlations to have the greatest clinical impact. Lastly, we assess a snapshot of integrated wireless wearable systems with multimodal sensing capabilities, and we conclude with our perspective on the state-of-the-art and the required developments to achieve the next-generation of integrated wearable health and performance monitoring systems.


Assuntos
Técnicas Biossensoriais , Dispositivos Eletrônicos Vestíveis , Eletrônica , Monitorização Fisiológica , Suor
10.
Biosens Bioelectron ; 176: 112933, 2021 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-33395570

RESUMO

The development of wearable multiplexed biosensors has been focused on systems to measure sweat l-lactate and other metabolites, where the employment of the direct electron transfer (DET) principle is expected. In this paper, a fusion enzyme between an engineered l-lactate oxidase derived from Aerococcus viridans, AvLOx A96L/N212K mutant, which is minimized its oxidase activity and b-type cytochrome protein was constructed to realize multiplexed DET-type lactate and glucose sensors. The sensor with a fusion enzyme showed DET to a gold electrode, with a limited operational range less than 0.5 mM. A mutation was introduced into the fusion enzyme to increase Km value and eliminate its substrate inhibition to construct "b2LOxS". Together with the employment of an outer membrane, the detection range of the sensor with b2LOxS was expanded up to 10 mM. A simultaneous lactate and glucose monitoring system was constructed using a flexible thin-film multiplexed electrodes with b2LOxS and a DET-type glucose dehydrogenase, and evaluated their performance in the artificial sweat. The sensors achieved simultaneous detection of lactate and glucose without cross-talking error, with the detected linear ranges of 0.5-20 mM for lactate and 0.1-5 mM for glucose, sensitivities of 4.1 nA/mM∙mm2 for lactate and 56 nA/mM∙mm2 for glucose, and limit of detections of 0.41 mM for lactate and 0.057 mM for glucose. The impact of the presence of electrochemical interferants (ascorbic acid, acetaminophen and uric acid), was revealed to be negligible. This is the first report of the DET-type enzyme based lactate and glucose dual sensing systems.


Assuntos
Técnicas Biossensoriais , Glicemia , Automonitorização da Glicemia , Eletrodos , Elétrons , Glucose , Glucose Oxidase , L-Lactato Desidrogenase
12.
Biosens Bioelectron ; 153: 112038, 2020 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-31989942

RESUMO

Comprehensive metabolic panels are the most reliable and common methods for monitoring general physiology in clinical healthcare. Translation of this clinical practice to personal health and wellness tracking requires reliable, non-invasive, miniaturized, ambulatory, and inexpensive systems for continuous measurement of biochemical analytes. We report the design and characterization of a wearable system with a flexible sensor array for non-invasive and continuous monitoring of human biochemistry. The system includes signal conditioning, processing, and transmission parts for continuous measurement of glucose, lactate, pH, and temperature. The system can operate three discrete electrochemical cells. The system draws 15 mA under continuous operation when powered by a 3.7 V 150 mAh battery. The analog front-end of the electrochemical cells has four potentiostats and three multiplexers for multiplexed and parallel readout from twelve working electrodes. Utilization of redundant working electrodes improves the measurement accuracy of sensors by averaging chronoamperometric responses across the array. The operation of the system is demonstrated in vitro by simultaneous measurement of glucose and lactate, pH, and skin temperature. In benchtop measurements, the sensors are shown to have sensitivities of 26.31 µA mM-1·cm-2 for glucose, 1.49 µA mM-1·cm-2 for lactate, 54 mV·pH-1 for pH, and 0.002 °C-1 for temperature. With the custom wearable system, these values were 0.84 ± 0.03 mV µM-1·cm-2 or glucose, 31.87 ± 9.03 mV mM-1·cm-2 for lactate, 57.18 ± 1.43 mV·pH-1 for pH, and 63.4 µV·°C-1 for temperature. This miniaturized wearable system enables future evaluation of temporal changes of the sweat biomarkers.


Assuntos
Técnicas Biossensoriais/instrumentação , Metaboloma/fisiologia , Monitorização Fisiológica/instrumentação , Dispositivos Eletrônicos Vestíveis , Dimetilpolisiloxanos/química , Técnicas Eletroquímicas , Eletrodos , Glucose/análise , Humanos , Concentração de Íons de Hidrogênio , Ácido Láctico/análise , Temperatura Cutânea , Propriedades de Superfície , Suor/química
13.
Congenit Anom (Kyoto) ; 60(5): 136-141, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31743503

RESUMO

The aims of this study were to determine the levels of trace elements and heavy metals, namely aluminum (Al), chromium (Cr), manganese (Mn), cobalt (Co), nickel (Ni), copper (Cu), zinc (Zn), arsenic (As), molybdenum (Mo), cadmium (Cd), tin (Sn), antimony (Sb), mercury (Hg), and lead (Pb), in the amniotic fluid of pregnant women, and to investigate their relationship with neural tube defects (NTDs). The study included 36 pregnant women whose fetuses were complicated with NTDs (study group) and 39 pregnant women with unaffected healthy fetuses (control group), who were matched for body mass index and gestational weeks. The amniotic fluid levels of trace elements and heavy metals were measured using inductively coupled plasma-mass spectrometry and compared between the two groups. Significantly lower mean levels of Zn and Mo and significantly higher levels of Al, Sn, Sb, and Hg in the study group than in the healthy control group were observed, which implied that these elements are possibly correlated with risk factors for the occurrence of NTDs. In contrast, there were no significant differences in the levels of Cr, Mn, Co, Ni, Cu, As, Cd, and Pb between the groups (P ≥ .05).


Assuntos
Líquido Amniótico/metabolismo , Biomarcadores , Metais Pesados/metabolismo , Defeitos do Tubo Neural/diagnóstico , Defeitos do Tubo Neural/metabolismo , Oligoelementos/metabolismo , Adulto , Estudos de Casos e Controles , Suscetibilidade a Doenças , Feminino , Humanos , Defeitos do Tubo Neural/etiologia , Gravidez , Adulto Jovem
14.
Angew Chem Int Ed Engl ; 58(33): 11285-11290, 2019 08 12.
Artigo em Inglês | MEDLINE | ID: mdl-31120567

RESUMO

Reaction pathways involving quantum tunneling of protons are fundamental to chemistry and biology. They are responsible for essential aspects of interstellar synthesis, the degradation and isomerization of compounds, enzymatic activity, and protein dynamics. On-surface conditions have been demonstrated to open alternative routes for organic synthesis, often with intricate transformations not accessible in solution. Here, we investigate a hydroalkoxylation reaction of a molecular species adsorbed on a Ag(111) surface by scanning tunneling microscopy complemented by X-ray electron spectroscopy and density functional theory. The closure of the furan ring proceeds at low temperature (down to 150 K) and without detectable side reactions. We unravel a proton-tunneling-mediated pathway theoretically and confirm experimentally its dominant contribution through the kinetic isotope effect with the deuterated derivative.

15.
Analyst ; 144(10): 3190-3215, 2019 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-30968094

RESUMO

As microfabrication techniques and tissue engineering methods improve, microphysiological systems (MPS) are being engineered that recapitulate complex physiological and pathophysiological states to supplement and challenge traditional animal models. Although MPS provide unique microenvironments that transcend common 2D cell culture, without proper regulation of oxygen content, MPS often fail to provide the biomimetic environment necessary to activate and investigate fundamental pathways of cellular metabolism and sub-cellular level. Oxygen exists in the human body in various concentrations and partial pressures; moreover, it fluctuates dramatically depending on fasting, exercise, and sleep patterns. Regulating oxygen content inside MPS necessitates a sensitive biological sensor to quantify oxygen content in real-time. Measuring oxygen in a microdevice is a non-trivial requirement for studies focused on understanding how oxygen impacts cellular processes, including angiogenesis and tumorigenesis. Quantifying oxygen inside a microdevice can be achieved via an array of technologies, with each method having benefits and limitations in terms of sensitivity, limits of detection, and invasiveness that must be considered and optimized. This article will review oxygen physiology in organ systems and offer comparisons of organ-specific MPS that do and do not consider oxygen microenvironments. Materials used in microphysiological models will also be analyzed in terms of their ability to control oxygen. Finally, oxygen sensor technologies are critically compared and evaluated for use in MPS.


Assuntos
Técnicas Analíticas Microfluídicas/métodos , Modelos Biológicos , Oxigênio/análise , Oxigênio/metabolismo , Animais , Linhagem Celular , Humanos , Dispositivos Lab-On-A-Chip , Técnicas Analíticas Microfluídicas/instrumentação
16.
Med Chem ; 14(3): 253-268, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-28969576

RESUMO

BACKGROUND: Acinetobacter is a Gram-negative, catalase-positive, oxidase-negative, non-motile, and no fermenting bacteria. OBJECTIVE: In this study, some of the electronic and molecular properties, such as the highest occupied molecular orbital energy (EHOMO), lowest unoccupied molecular orbital energy (ELUMO), the energy gap between EHOMO and ELUMO, Mulliken atomic charges, bond lengths, of molecules having impact on antibacterial activity against A. baumannii were studied. In addition, calculations of some QSAR descriptors such as global hardness, softness, electronegativity, chemical potential, global electrophilicity, nucleofugality, electrofugality were performed. METHOD: The descriptors having impact on antibacterial activity against A. baumannii have been investigated based on the usage of 29 compounds employing two statistical methods called Linear Regression and Artificial Neural Networks. RESULTS: Artificial Neural Networks obtained accuracies in the range of 83-100% (for active/inactive classifications) and q2=0.63 for regression. CONCLUSION: Three ANN models were built using various types of descriptors with publicly available structurally diverse data set. QSAR methodologies used Artificial Neural Networks. The predictive ability of the models was tested with cross-validation procedure, giving a q2=0.62 for regression model and overall accuracy 70-95 % for classification models.


Assuntos
Antibacterianos/química , Benzimidazóis/química , Relação Quantitativa Estrutura-Atividade , Acinetobacter baumannii/efeitos dos fármacos , Anisotropia , Concentração Inibidora 50 , Modelos Lineares , Testes de Sensibilidade Microbiana , Redes Neurais de Computação , Fosforilação Oxidativa , Teoria Quântica
17.
Int Ophthalmol ; 37(1): 245-249, 2017 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-27221265

RESUMO

The purpose of this study was to determine the effectiveness of ganciclovir ophthalmic gel (GOG) in the treatment of adenoviral eye infection (AEI) by looking at the effect of the drug on shortening recovery time, preventing transmission, reducing sequelae, and on complications such as corneal infiltrates and conjunctival pseudomembranes. 200 patients' examination records were evaluated retrospectively. Patients who were within the first 3 days of AEI were divided into two groups: Group 1 with 100 patients who used artificial tears as treatment, and Group 2 with 100 patients who used GOG plus artificial tears (GAT). All patients underwent an eye examination by the same ophthalmologist on the 1st, 5th, 10th, and 15th day after treatment. Using the examination records, variables were compared using SPSS 22.0. There was a statistically significant difference between Groups 1 and 2. Group 2 showed better and faster response to treatment. There was less transmission to the contralateral eye and environment, and less formation of corneal subepithelial infiltrate and conjunctival pseudomembrane in Group 2. Only three patients in Group 2 had corneal involvement. A comparison of each group pre-treatment and during treatment revealed improved signs and symptoms in Group 2 (p < 0.005). The study showed a trend toward more rapid improvement, less corneal and conjunctival involvement, and less transmission to the contralateral eye and environment in the GAT group. These results need to be confirmed by additional studies.


Assuntos
Infecções por Adenoviridae/tratamento farmacológico , Antivirais/administração & dosagem , Infecções Oculares Virais/tratamento farmacológico , Ganciclovir/administração & dosagem , Géis/uso terapêutico , Infecções por Adenoviridae/patologia , Adulto , Idoso , Túnica Conjuntiva/patologia , Córnea/patologia , Infecções Oculares Virais/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Soluções Oftálmicas/uso terapêutico , Estudos Retrospectivos
18.
J Clin Anesth ; 35: 404-410, 2016 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-27871565

RESUMO

STUDY OBJECTIVE: This study evaluated the postoperative analgesic efficacies of fascia iliaca block and periarticular drug injection techniques after TKA (total knee arthroplasty) surgeries. DESIGN: Prospective, randomized clinical trial. SETTING: University Teaching and Research Center. PATIENTS: Seventy-one American Society of Anesthesiologists (ASA) I-III patients between 48 and 70 years of age who underwent total knee arthroplasty were randomized. INTERVENTIONS: Tenoxicam (20 mg) was administered intramuscularly to both groups of patients 30 minutes before surgery. Patients were randomized into two groups to receive fascia iliaca block before the induction of anesthesia (Group FI) or periarticular drug injection during the surgery (Group PI). All surgeries were performed under general anesthesia using standard techniques. Postoperative analgesia was provided with patient-controlled intravenous morphine. MEASUREMENTS: Total morphine consumption was the primary outcome measure and was recorded postoperatively at 1, 2, 6, 12 and 24 hours. Pain levels at rest and on movement (knee flexion) were evaluated using the Visual Analogue Scale (VAS) and recorded at the same time points. Patients' demographics, rescue analgesic demands, side effects, hemodynamics, and satisfaction scores were also recorded. MAIN RESULTS: The groups had similar VAS scores both at rest and on movement (P>.05). However, the amount of cumulative morphine and use at each follow-up period was higher in Group PI (P<.0001). The groups did not differ significantly in rescue analgesic use or side effects, such as nausea/vomiting, hemodynamic variables, and patient satisfaction scores (P>.05). CONCLUSIONS: Fascia iliaca block may be used as an alternative method to periarticular injection, and it effectively reduces the amount of morphine used to relieve post-TKA pain.


Assuntos
Anestésicos Locais/administração & dosagem , Artroplastia do Joelho , Bloqueio Nervoso/métodos , Dor Pós-Operatória/tratamento farmacológico , Idoso , Bupivacaína/administração & dosagem , Fáscia/efeitos dos fármacos , Humanos , Injeções Intra-Articulares , Lidocaína/administração & dosagem , Pessoa de Meia-Idade , Estudos Prospectivos , Resultado do Tratamento
19.
IEEE Trans Biomed Eng ; 63(2): 423-30, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26241969

RESUMO

A flexible and conformable dry electrode design on nonwoven fabrics is examined as a sensing platform for biopotential measurements. Due to limitations of commercial wet electrodes (e.g., shelf life, skin irritation), dry electrodes are investigated as the potential candidates for long-term monitoring of ECG signals. Multilayered dry electrodes are fabricated by screen printing of Ag/AgCl conductive inks on flexible nonwoven fabrics. This study focuses on the investigation of skin-electrode interface, form factor design, electrode body placement of printed dry electrodes for a wearable sensing platform. ECG signals obtained with dry and wet electrodes are comparatively studied as a function of body posture and movement. Experimental results show that skin-electrode impedance is influenced by printed electrode area, skin-electrode interface material, and applied pressure. The printed electrode yields comparable ECG signals to wet electrodes, and the QRS peak amplitude of ECG signal is dependent on printed electrode area and electrode on body spacing. Overall, fabric-based printed dry electrodes present an inexpensive health monitoring platform solution for mobile wearable electronics applications by fulfilling user comfort and wearability.


Assuntos
Mapeamento Potencial de Superfície Corporal/instrumentação , Vestuário , Monitorização Ambulatorial/instrumentação , Têxteis , Adulto , Eletrodos , Desenho de Equipamento , Humanos , Masculino , Impressão
20.
Nat Struct Mol Biol ; 21(12): 1028-34, 2014 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-25383669

RESUMO

The evolutionarily conserved Mediator complex is a critical coactivator for RNA polymerase II (Pol II)-mediated transcription. Here we report the reconstitution of a functional 15-subunit human core Mediator complex and its characterization by functional assays and chemical cross-linking coupled to MS (CX-MS). Whereas the reconstituted head and middle modules can stably associate, basal and coactivator functions are acquired only after incorporation of MED14 into the bimodular complex. This results from a dramatically enhanced ability of MED14-containing complexes to associate with Pol II. Altogether, our analyses identify MED14 as both an architectural and a functional backbone of the Mediator complex. We further establish a conditional requirement for metazoan-specific MED26 that becomes evident in the presence of heterologous nuclear factors. This general approach paves the way for systematic dissection of the multiple layers of functionality associated with the Mediator complex.


Assuntos
Complexo Mediador/metabolismo , Mapas de Interação de Proteínas , Clonagem Molecular , Células HeLa , Humanos , Complexo Mediador/química , Complexo Mediador/genética , Subunidades Proteicas/química , Subunidades Proteicas/genética , Subunidades Proteicas/metabolismo , RNA Polimerase II/metabolismo , Ativação Transcricional
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