Publications

Objectives: A population Japanese study suggested that a diminished nighttime decline in blood pressure (BP) (non-dipper pattern) is a risk factor for cardiovascular mortality independent of the 24 h mean BP level [J Hypertens. 2002;20:2183–9]. We compared the relative influence of the BP level and the sleep-time relative BP decline as contributing factors for cardiovascular morbidity and mortality in the MAPEC study, designed to investigate whether increasing the sleep-time relative BP decline results in reduced cardiovascular risk. Methods: This prospective study investigated 3344 subjects (1718 men), 52.6 ± 14.5 years of age. At baseline, BP was measured every 20-min from 07:00 to 23:00 h and every 30-min at night for 48 h. Subjects were classified as having elevated BP if the awake mean was >135/85 mmHg for systolic/diastolic BP or the asleep mean >120/70 mmHg, and of normal BP otherwise. The Cox proportional-hazard model was used to estimate relative risks of cardiovascular events associated to elevated BP and/or diminished sleep-time relative BP decline. Results: After a median time of follow-up of 5.6 years and with adjustment for significant confounding factors including gender, age, antihypertensive treatment and diabetes, the relative hazard ratio of cardiovascular events for dipper subjects with elevated BP as compared to dipper subjects with normal BP was 1.57 (95% confidence interval [1.03–2.39]; P = 0.036). Subjects with a non-dipper BP pattern had higher cardiovascular risk, whether BP was within the normotensive range (1.95 [1.33–2.87]; P < 0.001; P = 0.218 compared to dipper subjects with elevated BP) or above it (4.01 [2.89–5.56]; P < 0.001). Conclusions: Cardiovascular risk is more closely related to a diminished sleep-time relative BP decline than to an elevated BP. Among subjects with BP in the normotensive range, non-dippers have twofold cardiovascular risk than dippers. Moreover, cardiovascular risk was 40% higher for non-dippers with normal BP (who would not be treated according to current guidelines) than for dippers with elevated BP. ABPM is a diagnostic technique that should be extended and recommended for proper cardiovascular risk assessment.

The prevalence and clinical significance of white coat hypertension (WCH) is still controversial. Although recent longitudinal studies have provided preliminary prognostic data on subjects with WCH as compared to patients with sustained hypertension, the possible relation between WCH and vascular risk is still under debate. Accordingly, we compared the circadian pattern of blood pressure (BP) variability between normotensive subjects and patients with WCH. We studied 186 subjects (85 mean), 49.5±14.7 (mean±SD) years of age, with diurnal BP mean below 135/85 for systolic/diastolic BP, and hyperbaric index (area of BP excess above a time-specified tolerance interval) below the previously established threshold for diagnosis of hypertension from data obtained by ambulatory BP monitoring [Hermida et al. Hypertension. 2000;35:118-125]. Among those subjects, 94 (47 men) had WCH (mean from 6 office BP measurements above 140 or 90 mm Hg for systolic or diastolic BP). BP was measured at 20-minute intervals during the day (07:00 to 23:00 hours) and at 30-minute intervals at night for 48 consecutive hours. Circadian parameters established by population multiple-component analysis [Fernandez & Hermida. Chronobiol Int. 1998;15:191-204] were compared between normotensive and WCH subjects by nonparametric testing. Patients with WCH are characterize by a significant increase in systolic (3.1 mm Hg; P<0.001) but not in diastolic BP (P=0.452 for comparison of 24-hour mean) as compared to normotensive subjects. The differences in systolic BP between normotension and WCH are much more pronounced during the first 6 hours after awakening, and they are almost irrelevant during nocturnal resting hours. The largest and highly significant difference between groups was found around the clock in pulse pressure (about 4 mm Hg in 24-hour mean, P<0.001). In patients studied by 48-hour ambulatory monitoring, WCH is characterized by a significant elevation in systolic BP and, especially, in pulse pressure as compared to truly normotensive subjects. If indeed pulse pressure is an independent predictor of risk and cardiovascular events, WCH could then be associated to a long-term worst prognosis in comparison to true normotension, an issue that deserves further investigation. DGES, PM98-0106; PGICT00-PXI-32205PN; University of Vigo.

A simple, rapid, and visual approach is developed to perform diagnosis of urinary tract infection (UTI) and antimicrobial susceptibility testing (AST) by employing smart bifunctional DNA (bfDNA) sensors, exonuclease III, concatermers of CuO nanoparticles (CuONPs), and gold NPs (AuNPs) aggregation [AuNPs agglutination (AA)], namely, the bfDEC-AA method. The bfDNA sensors serve as probes for identifying 16S rRNA genes of bacterium or 18S rRNA of fungus and as mediators connecting the concatermers of CuONPs. The AA as a signal source is triggered by Cu(I)-catalyzed azide-alkyne cycloaddition click chemistry. In this study, the urine samples are analyzed directly, eliminating the need for overnight incubation or bacterial isolation. A crucial color change from red to purple occurs at the UTI diagnostic threshold of 10⁴ CFU mL^-1; thus the results of UTI diagnosis can be qualitatively interpreted by the unaided eyes. Similarly, AST was performed visually under our optimal conditions. The color shift can also be quantified using a point-of-care (POC) device. UTI identification, bacteria strain identification, and AST were achieved within 55, 55, and 145 min for 96 samples, respectively. Here, 128 urine samples from suspected UTI patients were tested. Notably, the sensitivity and specificity of our method were 99% and 100% for Gram-negative bacteria (G^-) infection, 100% and 100% for Gram-positive bacteria (G⁺) infection, and 98% and 100% for AST, respectively. Furthermore, the low cost of our POC device (US$156) is friendly to underdeveloped regions.

The volume phase transition of colloidal microgels made of N-isopropylacrylamide (NIPAM) is well-studied and it is known that the transition temperature can be influenced by copolymerization. A series of poly( N-isopropylacrylamide- co-allylacetic acid) copolymers with different contents of allylacetic acid (AAA) was synthesized by means of a simple radical polymerization approach. The thermoresponsive behavior of these particles was studied using dynamic light scattering (DLS). Further characterization was done by employing transmission electron microscopy (TEM) and zeta potential measurements. TEM observations reveal the approximately spherical shape and low polydispersity of the copolymer particles. In addition, the measured zeta potentials provide information about the relative surface charge. Since these copolymers are much more sensitive to external stimuli such as pH and ionic strength than their pure PNIPAM counterparts, the volume phase transition was investigated at two different pH values and various salt concentrations. At pH 10 for the copolymer microgels with the highest AAA content, a significant shift of the volume phase transition temperature toward higher values is found. For higher AAA content, a change in pH from 8 to 10 can induce a change in radius of up to 100 nm making the particles interesting as pH controlled actuators.

Abstract Motivation: Phylogenetic and evolutionary inference can be severely misled if recombination is not accounted for, hence screening for it should be an essential component of nearly every comparative study. The evolution of recombinant sequences can not be properly explained by a single phylogenetic tree, but several phylogenies may be used to correctly model the evolution of non-recombinant fragments. Results: We developed a likelihood-based model selection procedure that uses a genetic algorithm to search multiple sequence alignments for evidence of recombination breakpoints and identify putative recombinant sequences. GARD is an extensible and intuitive method that can be run efficiently in parallel. Extensive simulation studies show that the method nearly always outperforms other available tools, both in terms of power and accuracy and that the use of GARD to screen sequences for recombination ensures good statistical properties for methods aimed at detecting positive selection. Availability: Freely available Contact: spond@ucsd.edu

The increased efficacy on ambulatory BP as well as the significantly reduced prevalence of edema after bedtime as compared to morning ingestion of nifedipine should be taken into account when prescribing this medication to patients with essential hypertension.

The purpose of this communication is to respond to the continuing invalid criticism by Lemmer and Middeke of the MAPEC and Hygia Chronotherapy Trial by emphasizing the: (i) already unambiguously reported ambulatory blood pressure monitoring (ABPM)-based definition of hypertension utilized as <b><i>the</i></b> inclusion criterion of both investigations and (ii) impact of bedtime hypertension chronotherapy on ABPM-assessed parameters and cardiovascular disease (CVD) outcome for participants further categorized by influential markers of CVD risk. In so doing, we call attention to apparent unethical misconduct of Lemmer and Middeke of multiple duplicated publications of the very same unfounded criticisms.