Modeling the circadian variability of ambulatorily monitored blood pressure by multiple-component analysis

The use of a set of new end points derived from ambulatory blood pressure monitoring (ABPM), in addition to the blood pressure (BP) values themselves, has been advocated to improve the sensitivity and specificity in diagnosing hypertension and to evaluate a person's response to treatment. An adequate estimation of rhythmic parameters depends, however, on the ability to describe properly the circadian pattern of BP variability. The purpose of this study was to identify a simple model that could characterize sufficiently well the circadian pattern of BP in normotensive healthy volunteers sampled by ambulatory monitoring. We studied 278 clinically healthy Spanish adults (184 men), 22.7±3.3 yr of age, without medical history of hypertension and mean BP from ambulatory profiles always below 135/85 mmHg for systolic/diastolic BP, who underwent sequential ABPM providing a total of 1115 series of BPs and heart rates (HRs), sampled on each occasion at 0.5h intervals for 48 h. Subjects were assessed while adhering to their usual diurnal activity and nocturnal sleep routine, without restrictions but avoiding the use of medication. The circadian rhythm in BP and HR for each subject was established by multiple-component analysis. A statistically significant 24h component is documented for 97% of the BP profiles, with a significant second (12h) harmonic documented in 65% of the profiles. Other ultradian harmonic components were significant in less than 20% of the profiles. A statistically significant increase in the coefficient of determination (percent of overall variability explained by the function fitted to the data) was only obtained after including the periods of 24 and 12 h for BP, and periods of 24, 12, and 6 h for HR in the model components. Although other ultradian components can be demonstrated as statistically significant in a small percent of subjects, a rather simple model including only the two first harmonics of the 24h period describes sufficiently well, at the specified sampling rate, the circadian pattern of BP in normotensive subjects. Departure from this model could characterize overt pathology, as recently demonstrated in the diagnosis of preeclampsia.     

Circadian Rhythm of Blood Pressure Challenges Office Values as the “Gold Standard” in the Diagnosis of Gestational Hypertension

Despite poor sensitivity and specificity, office blood pressure (BP) determinations are still the “gold standard” for diagnosing gestational hypertension. This prospective blind study evaluates the prognostic value of office values as compared with ambulatory monitoring in pregnancy. We analyzed 2175 BP series systematically sampled from 355 non-preeclamptic pregnant women for 48 h every 4 wks from the first hospital visit until delivery. Women were divided for comparative purposes into three groups: “detected” gestational hypertension, defined on the basis of casual clinical BP>140/90 mm Hg after 20 wks of gestation and hyperbaric index (area of BP excess above the upper limit of a time-specified tolerance interval adjusted for the circadian pattern of the reference population) consistently above the threshold for diagnosing hypertension in pregnancy; “undetected” gestational hypertension, women with office BP<140/90 mm Hg but hyperbaric index consistently above the threshold for diagnosis; and normotension, women with both office values and hyperbaric index below the respective thresholds for diagnosis. Small and insignificant differences in the 24 h mean BP between “detected” and “undetected” gestational hypertension is observed in all trimesters, in contrast with highly significant differences between these two groups and normotensive pregnancies. Normotensive women are characterized by highly significant lesser incidence by 60% in preterm delivery, 70% in intrauterine growth retardation, and 50% in delivery by cesarean section (P<0.001) compared with women with “detected” and “undetected” gestational hypertension (P>0.715). In pregnancy, the hyperbaric index is markedly superior to office BP measurements for diagnosis of what should be truly considered gestational hypertension, and for prediction of the outcome of pregnancy.     

Analysis of eighteen antidepressants,four atypical antipsychotics and active metabolites in serum by liquid chromatography: a simple tool for therapeutic drug monitoring

Therapeutic drug monitoring necessitates efficient, fast and reliable analytical methods validated by external quality control. We therefore devised an isocratic reversed-phase HPLC method with ultraviolet detection and optimised this to quantify mirtazapine, reboxetine, moclobemide, venlafaxine, O-desmethylvenlafaxine, paroxetine, fluvoxamine, fluoxetine, norfluoxetine, sertraline, citalopram, amitriptyline, nortriptyline, imipramine, desipramine, doxepin, nordoxepin, clomipramine, norclomipramine, trimipramine, mianserine, maprotiline, normaprotiline, amisulpride, clozapine, norclozapine, quetiapine, risperidone and 9-OH-risperidone in human serum. After solid-phase extraction of the drugs and metabolites, the chromatographic separation was achieved on a Nucleosil 100-Protect 1 column with acetonitrile-potassium dihydrogenphosphate buffer as mobile phase. The method was validated for therapeutic and toxic serum ranges. A linear relationship (r>0.998) was obtained between the concentration and the detector signal. Recoveries were between 75 and 99% for the drugs and metabolites. The accuracy of the quality control samples, expressed as percent recovery, ranged from 91 to 118%; intra- and inter-assay-relative standard deviations were 0.9-10.2% and 0.9-9.7%, respectively. Additional external quality control is carried out since 3 years. This method is applicable to rapidly and effectively analyze serum or plasma samples for therapeutic drug monitoring of about 30 antidepressants and atypical antipsychotics.     

我国韭菜主产区韭菜迟眼蕈蚊田间种群的抗药性监测

【目的】建立韭菜迟眼蕈蚊Bradysia odoriphaga Yang et Zhang对10种常用药剂的敏感基线,并对4省7个主要韭菜产区的田间种群进行6种常用杀虫剂的抗药性水平监测。【方法】采用胃毒触杀联合毒力法对韭菜迟眼蕈蚊3龄幼虫进行室内生物测定。【结果】建立了敏感品系对新烟碱类、有机磷类、菊酯类、昆虫生长调节剂类、吡咯类药剂的敏感基线。对7个地区的田间韭菜迟眼蕈蚊种群监测结果表明:其对有机磷类药剂均产生了抗药性,其中河南郑州种群对毒死蜱和辛硫磷产生了极高水平抗性;河南郑州种群对高效氯氰菊酯产生了中等水平抗性,其他各地区均处于敏感状态;大部分种群对新烟碱类药剂处于低等或中等水平抗性,但山东李坡种群对噻虫嗪产生了高水平抗性。【结论】本文建立的韭菜迟眼蕈蚊对10种杀虫剂的敏感基线及抗药性监测数据为抗性治理提供一定参考。     

Development of a Flooded Forest Anthropization Index (FFAI) applied to Amazonian areas under pressure from different human activities

The floodplain forests in the Amazon basin suffer from the continued exploitation of natural resources and, after being disturbed, show slow and sometimes irreversible recovery. Our goal was to create an index that could be used to assess the relative level of human disturbance in floodplain forests and determine the relative importance of different types of disturbance on a given site and between sites. The index proposed here (Flooded Forest Anthropization Index – FFAI) assesses human disturbance on a local scale and is composed by 15 indicators divided into three groups that represent different levels of impact: (1) simplification of ecosystems and reduction of local diversity; (2) ecosystem replacement/destruction; (3) disturbances with the potential to impact the ecosystem in both ways. The FFAI proved to be robust and revealed a wide range of values in the evaluated landscapes. The sites classified a priori as more anthropogenic showed significantly higher FFAI values than the less anthropogenic ones (0.14 ± 0.05 and 0.08 ± 0.02, respectively, F = 18.9, df = 19, p < 0.0001). The FFAI enabled a comprehensive assessment of human disturbance on a local scale in Amazonian floodplain forests and can be a useful tool for decision makers in choosing priority areas for interventions and for targeting the type of intervention that must be carried out. Although specific to floodplains, the index can be adjusted to be used in other ecosystems.     

磁纳米颗粒标记脂肪干细胞向软骨分化及体外MRI示踪的实验研究

目的:探讨磁纳米颗粒(magnetic iron oxide particles,MIOP)体外标记脂肪间充质干细胞(ASCs)向软骨分化及MRI示踪的可行性。方法:从小鼠脂肪组织中分离培养、扩增脂肪间充质干细胞(ASCs),流式鉴定细胞表型后,分别采用不同浓度(25μg/mL,50μg/mL)的MIOP标记ASCs并向软骨细胞诱导分化。普鲁士蓝染色和透射电镜(TEM)鉴定细胞内磁纳米铁颗粒分布情况,应用3.0T MRI体外检测标记软骨细胞MRI信号。结果:从脂肪组织中可以分离获得大量高表达CD90、CD105、Sca-1的ASCs,不同浓度(25μg/mL,50μg/mL)的MIOP与ASCs共同孵育24小时后,普鲁士蓝染色发现ASCs随MIOP浓度的增加,蓝染程度逐渐加深且标记的ASCs可以向软骨细胞分化;TEM证实细胞内分布大量的黑色纳米铁颗粒。体外MRI T2序列证实随着MIOP浓度(25μg/mL,50μg/mL)的增加MRI信号值逐渐减低且具有统计学差异(P0.05)。结论:MIOP可以标记ASCs向软骨分化,体外应用MRI可以对其进行示踪。     

Odontocete occurrence in relation to changes in oceanography at a remote equatorial Pacific seamount

Seamounts are considered hot spots of biodiversity and can aggregate pelagic predators and their prey. Passive acoustic monitoring was conducted over 3 mo in 2012 to document the occurrence of odontocetes near a seamount chain in the central equatorial Pacific in relation to oceanographic changes over time. Beaked whale echolocation signals were most frequently encountered. The main beaked whale signal was an unknown type, BW38, which resembled signals produced by Blainville's beaked whales. It had high occurrence during high sea surface temperature and low sea surface salinity. Cuvier's beaked whales were the second most detected. They had an opposite pattern and were encountered more often when sea surface temperature was low and net primary productivity was high. Risso's dolphins and short‐finned pilot whales had high acoustic densities, and echolocated predominantly at night. Risso's dolphins occurred more often during low sea surface height deviation. False killer whales were less frequently detected and mostly occurred during the day. Sperm whale detections were fewer than expected and associated with high chlorophyll a. Short duration Kogiidae encounters occurred on average every third day. These types of long‐term site studies are an informative tool to comparatively assess species composition, relative abundance, and relationship to oceanographic changes.     

The clinical impact of recent advances in LC-MS for cancer biomarker discovery and verification

Mass spectrometry (MS) -based proteomics has become an indispensable tool with broad applications in systems biology and biomedical research. With recent advances in liquid chromatography (LC) and MS instrumentation, LC–MS is making increasingly significant contributions to clinical applications, especially in the area of cancer biomarker discovery and verification. To overcome challenges associated with analyses of clinical samples (for example, a wide dynamic range of protein concentrations in bodily fluids and the need to perform high throughput and accurate quantification of candidate biomarker proteins), significant efforts have been devoted to improve the overall performance of LC–MS-based clinical proteomics platforms. Reviewed here are the recent advances in LC–MS and its applications in cancer biomarker discovery and quantification, along with the potentials, limitations and future perspectives.     

Two Cases of Recovery of Dimorphic Pathogenic Fungi via Conventional BacT/ALERT<Superscript>®</Superscript> Microbial Detection System Media

We hereby report two instances of dimorphic fungus cultivation in BacT/ALERT^®-based bacteriologic media, with the first such characterization of Blastomyces dermatitidis. From a patient with disseminated coccidioidomycosis, routine blood cultures incubated on the MB/BacT^® 3D^? Microbial Detection System generated a positive signal following 75 h of incubation. B. dermatitidis was isolated from a patient hospitalized with a four-week course of respiratory illness. Organism detection from respiratory specimens via the MB/BacT^® 3D^? Mycobacteria Detection System occurred 5 days sooner than the routine fungus culture. Etiologic agents of endemic mycoses may be isolated in bacteriologic media employed by continuous monitoring instrumentation.