Publications

Abstract The relationship between the structural properties of selected dietary flavanoids and flavonoids and their affinities for HSA were investigated by fluorescence analysis. The binding process with HSA was strongly influenced by the structural differences of the compounds under study. Methylation of hydroxyl groups improved the affinities for HSA by 2–16‐fold. Hydroxylation on rings A, B, and C also affected the affinity for HSA significantly. Glycosylation decreased the affinities for HSA by 1–3 orders of magnitude depending on the conjugation site and the class of sugar moiety. Hydrogenation of the C2=C3 double bond also decreased the binding affinity. Galloylated catechins and pyrogallol‐type catechins exhibited higher binding affinities for HSA than non‐galloylated and catechol‐type catechins, respectively. The affinities for HSA increased with increasing partition coefficients and decreased with increasing hydrogen bond donor and acceptor numbers of flava(o)noids, which suggested that the binding interaction was mainly caused by hydrophobic forces.

The performance of 14 different recombination detection methods was evaluated by analyzing several empirical data sets where the presence of recombination has been suggested or where recombination is assumed to be absent. In general, recombination methods seem to be more powerful with increasing levels of divergence, but different methods showed distinct performance. Substitution methods using summary statistics gave more accurate inferences than most phylogenetic methods. However, definitive conclusions about the presence of recombination should not be derived on the basis of a single method. Performance patterns observed from the analysis of real data sets coincided very well with previous computer simulation results. Previous recombination inferences from some of the data sets analyzed here should be reconsidered. In particular, recombination in HIV-1 seems to be much more widespread than previously thought. This finding might have serious implications on vaccine development and on the reliability of previous inferences of HIV-1 evolutionary history and dynamics.

Patients with resistant hypertension (RH) are at greater risk for stroke, renal insufficiency, and cardiovascular disease (CVD) events than are those for whom blood pressure (BP) is responsive to and well controlled by therapeutic interventions. Although all chronotherapy trials have compared the effects on BP regulation of full daily doses of medications when ingested in the morning versus at bedtime, prescription of the same medications in divided doses twice daily (BID) is frequent. Here, we investigated the influence of hypertension treatment-time regimen on the circadian BP pattern, degree of BP control, and relevant clinical and laboratory medicine parameters of RH patients evaluated by 48-h ambulatory BP monitoring (ABPM). This cross-sectional study evaluated 2899 such patients (1701 men/1198 women), 64.2 ± 11.8 (mean ± SD) yrs of age, enrolled in the Hygia Project. Among the participants, 1084 were ingesting all hypertension medications upon awakening (upon-awakening regimen), 1436 patients were ingesting the full daily dose of ≥1 of them at bedtime (bedtime regimen), and 379 were ingesting split doses of ≥1 medications BID upon awakening and at bedtime (BID regimen). Patients of the bedtime regimen compared with the other two treatment-time regimens had lower likelihood of microalbuminuria and chronic kidney disease; significantly lower albumin/creatinine ratio, glucose, total cholesterol, and low-density lipoprotein (LDL) cholesterol; plus higher estimated glomerular filtration rate and high-density lipoprotein (HDL) cholesterol. The bedtime regimen was also significantly associated with lower asleep systolic (SBP) and diastolic (DBP) BP means than the upon-awakening and BID regimens. The sleep-time relative SBP and DBP decline was significantly attenuated by the upon-awakening and BID regimens (p < .001), resulting in significantly higher prevalence of non-dipping in these two treatment-time regimen groups (80.5% and 77.3%, respectively) than in the bedtime regimen (54.4%; p < .001 between groups). Additionally, the prevalence of the riser BP pattern, associated with highest CVD risk, was much greater, 31.0% and 29.8%, respectively, among patients of the upon-awakening and BID-treatment regimens, compared with the bedtime regimen (17.6%; p < .001 between groups). Patients of the bedtime regimen also showed significantly higher prevalence of properly controlled ambulatory BP (p < .001) as a result of a greater proportion of them showing complete control of asleep SBP and DBP means. Our findings demonstrate significantly lower asleep SBP and DBP means and attenuated prevalence of blunted nighttime BP decline, i.e., lower prevalence of CVD risk markers, in RH patients ingesting the full daily dose of ≥1 hypertension medications at bedtime than in those ingesting all of them upon awakening or ≥1 of them as split doses BID. In RH, ingesting the same medications BID neither improves ambulatory BP control nor reduces the prevalence of non-dipping, and cannot be considered chronotherapy. Collectively, findings of this study indicate that a bedtime hypertension medication regimen, in conjunction with proper patient evaluation by ABPM to corroborate the diagnosis of true RH and avoid treatment-induced nocturnal hypotension, should be the therapeutic scheme of choice for patients who, by conventional cuff methods (and in the absence of ABPM) and the morning-treatment regimen, have been mistakenly judged to be resistant to therapy.

Abstract We investigate the impact of antagonistic pleiotropy on the most widely used methods of estimation of the average coefficient of dominance of deleterious mutations from segregating populations. A proportion of the deleterious mutations affecting a given studied fitness component are assumed to have an advantageous effect on another one, generating overdominance on global fitness. Using diffusion approximations and transition matrix methods, we obtain the distribution of gene frequencies for nonpleiotropic and pleiotropic mutations in populations at the mutation-selection-drift balance. From these distributions we build homozygous and heterozygous chromosomes and assess the behavior of the estimators of dominance. A very small number of deleterious mutations with antagonistic pleiotropy produces substantial increases on the estimate of the average degree of dominance of mutations affecting the fitness component under study. For example, estimates are increased three- to fivefold when 2% of segregating loci are overdominant for fitness. In contrast, strengthening pleiotropy, where pleiotropic effects are assumed to be also deleterious, has little effect on the estimates of the average degree of dominance, supporting previous results. The antagonistic pleiotropy model considered, applied under mutational parameters described in the literature, produces patterns for the distribution of chromosomal viabilities, levels of genetic variance, and homozygous mutation load generally consistent with those observed empirically for viability in Drosophila melanogaster.

Some studies based on ambulatory blood pressure (BP) monitoring (ABPM) have reported a reduction in sleep-time relative BP decline towards a more non-dipping pattern in the elderly, but rarely have past studies included a proper comparison with younger subjects, and no previous report has evaluated the potential role of hypertension treatment time on nighttime BP regulation in the elderly. Accordingly, we evaluated the influence of age and time-of-day of hypertension treatment on the circadian BP pattern assessed by 48-h ABPM. This cross-sectional study involved 6147 hypertensive patients (3108 men/3039 women), 54.0 ± 13.7 (mean ± SD) yrs of age, with 2137 (978 men/1159 women) being ≥60 yrs of age. At the time of study, 1809 patients were newly diagnosed and untreated, and 4338 were treated with hypertension medications. Among the later, 2641 ingested all their prescribed BP-lowering medications upon awakening, whereas 1697 ingested the full daily dose of ≥1 hypertension medications at bedtime. Diagnosis of hypertension in untreated patients was based on ABPM criteria, specifically an awake systolic (SBP)/diastolic (DBP) BP mean ≥135/85 mm Hg and/or an asleep SBP/DBP mean ≥120/70 mm Hg. Collectively, older in comparison with younger patients were more likely to have diagnoses of microalbuminuria, chronic kidney disease, obstructive sleep apnea, metabolic syndrome, anemia, and/or obesity. In addition, the group of older vs. younger patients had higher glucose, creatinine, uric acid, triglycerides, and fibrinogen, but lower cholesterol, hemoglobin, and estimated glomerular filtration rate. In older compared with younger patients, ambulatory SBP was significantly higher and DBP significantly lower (p < .001), mainly during the hours of nighttime sleep and initial hours after morning awakening. The prevalence of non-dipping was significantly higher in older than younger patients (63.1% vs. 41.1%; p < .001). The largest difference between the age groups was in the prevalence of a riser BP pattern, i.e., asleep SBP mean greater than awake SBP mean (19.9% vs. 4.9% in older vs. younger patients, respectively; p < .001). The sleep-time relative SBP decline was mainly unchanged until ~40 yrs of age, and then significantly and progressively decreasing with increasing age at a rate of .28%/yr (p < .001), reaching a minimum value of 4.38% ± .47% for patients ≥75 yrs of age. Treated compared with untreated patients showed lower awake and asleep SBP means, although the predictable changes of SBP and DBP with age were equivalent in both groups. As a consequence, there were no significant differences between untreated and treated patients in the changes of the sleep-time relative SBP and DBP declines with age. Additionally, the asleep SBP and DBP means were significantly lower and the sleep-time relative SBP and DBP declines significantly higher at all ages in patients ingesting ≥1 BP-lowering medications at bedtime as compared with those ingesting all medications upon awakening. Our findings document a significantly elevated prevalence of a blunted nighttime BP decline with increasing age ≥40 yrs. The prevalence of a riser BP pattern, associated with highest cardiovascular risk among all possible BP patterns, was 4 times more prevalent in patients ≥60 yrs of age than those <60 yr of age. Most important, there was an attenuated prevalence of a blunted nighttime BP decline at all ages when ≥1 hypertension medications were ingested at bedtime as compared with when all of them were ingested upon awakening. These findings indicate that older age should be included among the conditions for which ABPM is recommended for proper cardiovascular risk assessment.

Abstract Four flavones (flavone, 7‐hydroxyflavone, chrysin, and baicalein) sharing the same B‐ and C‐ring structure but a different numbers of hydroxyl groups on the A‐ring were studied for their affinities for BSA and HSA. The hydroxylation on ring A of flavones increased the binding constants ( K a ) and the number of binding sites ( n ) between flavones and serum albumins. The affinities of 7‐hydroxyflavone for BSA and HSA were about 800 times and 40 times higher than that of flavone, respectively. It appears that the optimal number of hydroxyl groups introduced to the ring A of flavones is one. As more hydroxyl groups were introduced to positions at C‐5, C‐6, and/or C‐7 of flavones, the affinities for serum albumins decrease. The critical energy transfer distances ( R 0 ) between the hydroxylated flavones (1–3 OH on the ring A) and serum albumins decreased with the increasing affinities for serum albumins.

En la actualidad, las empresas requieren de la obtención de datos precisos, análisis que apoye en la toma de decisiones y en la mejora continua; estos procesos han llegado a formar parte de la visión de negocios de la gerencia empresarial sobre la cual están orientados los objetivos de negocios para poder ser y permanecer competitivos. Las empresas de manufactura tienen la necesidad de obtener y analizar datos relacionados a los procesos de producción para determinar el nivel de eficiencia de estos y en base a la información obtenida tomar decisiones que ayuden a la empresa a mejorar o corregir situaciones que puedan ser de carácter humano, operativo, procedural o de equipo. En este proyecto de desarrollo de software se ha diseñado e implementado un sistema de información, con el método de cascada, para una empresa de manufactura localizada en la frontera norte de México con Estados Unidos en el sector del cuidado de la salud; el sistema utiliza datos desde un controlador lógico programable, en el cual se obtienen datos para su monitoreo como: alarmas de la máquina, conteo de eventos, duración de cada alarma y velocidad de producción. Dando como resultado información de los códigos de producción, turno, día y hora; además de medir de forma precisa la eficiencia de la máquina, así como la detección de tendencias y la creación de alertas oportunas hacia personas técnicas para la solución de problemas. El sistema consta de un análisis de velocidad y carga de trabajo del procesador del PLC, desarrollo de la conexión entre el procesador y el sistema, preparación del sistema para el traspaso de información, programación de la base de datos en Access y el diseño de la interfaz gráfica en Visual Basic. Net. Entre los logros más importantes obtenidos de la implementación del sistema de información se encuentran: Disponibilidad de la información en tiempo real y obtención de datos históricos de las variables de producción del equipo, mejoramiento de las tareas de supervisión y control de procesos, así como el envío de alertas a usuarios específicos para reacción adecuada a eventos de fallas. Currently, companies require obtaining accurate data, analysis that supports decision-making and continuous improvement; these processes have become part of the business management vision on which business objectives are oriented to be and remain competitive. Manufacturing companies have the need to obtain and analyze data related to production processes to determine their level of efficiency and based on the information obtained, make decisions that help the company improve or correct situations that may be of human, operational, procedural or equipment. In this software development project, with the cascade method, an information system has been designed and implemented, for a manufacturing company located on the northern border of Mexico with the United States in the health care sector; the system uses data from a programmable logic controller, in which data such as: machine alarms, event count, duration of each alarm, and production speed were obtained for monitoring. Resulting in information on the production codes, shift, day and hour; in addition to accurately measuring the efficiency of the machine, as well as the detection of trends and the creation of timely alerts to technical personnel for troubleshooting. The system consists of an analysis of the speed and workload of the PLC processor, development of the connection between the processor and the system, preparation of the system for the transfer of information, programming of the database and the design of a graphical interface in Visual Basic.Net . Among the most important achievements obtained from the implementation of the information system are: Availability of information in real time and obtaining historical data from production variables, improvement of supervision tasks and process control, as well such as sending alerts to specific users for adequate reaction to failure events.