Neoexpression of ACE by renal endothelial cells, as well as changes of the tubular ACE content, is a common finding in diseased human kidneys. As associated with certain tissue sites, clinical and/or morphological features, these changes may be involved in parenchymal remodeling and renal pathophysiology.

Acute physical exercise and repeated exercise stimuli affect whole-body metabolic and immunologic homeostasis. The aim of this study was to determine plasma protein profiles of trained (EET, n = 19) and untrained (SED, n = 17) individuals at rest and in response to an acute bout of endurance exercise. Participants completed a bicycle exercise test at an intensity corresponding to 80% of their VO2max. Plasma samples were taken before, directly after, and three hours after exercise and analyzed using multiplex immunoassays. Seventy-eight plasma variables were included in the final analysis. Twenty-nine variables displayed significant acute exercise effects in both groups. Seven proteins differed between groups, without being affected by acute exercise. Among these A2Macro and IL-5 were higher in EET individuals while leptin showed elevated levels in SED individuals. Fifteen variables revealed group and time differences with elevated levels for IL-3, IL-7, IL-10, and TNFR2 in EET individuals. An interaction effect could be observed for nine variables including IL-6, MMP-2, MMP-3, and muscle damage markers. The proteins that differ between groups indicate a long-term exercise effect on plasma protein concentrations. These findings might be of importance in the development of exercise-based strategies in the prevention and therapy of chronic metabolic and inflammatory diseases and for training monitoring.

591CliNiCal artiCle J Neurosurg 125:591-597, 2016 I dIopathIc normal pressure hydrocephalus (iNPH) has been a challenging entity for the past 50 years, since its first description by Hakim.21 Despite extensive research, its pathophysiological basis and pathogenesis remain matters of ongoing debate. Due to the uncertainty in diagnostic measures, several algorithms, diagnostic tools, and scoring systems have been proposed. A recent multicenter trial based the decision for surgical therapy on clinical signs and symptoms only, dividing cases into questionable and typical iNPH.23 Given the multitude of noninvasive and invasive measures to select symptomatic patients for hydrocephalus therapy, a prospective analysis of diagnostic and predictive parameters and their individual contributions within the diagnostic algorithm was warranted. Patients and MethodsPatients with suspicious clinical and MRI signs for iNPH were examined in a prospective study. Local ethics committee approval was obtained.abbreviatioNs AMP Q = ICP amplitude quotient; ELD = external lumbar drainage; ETV = endoscopic third ventriculostomy; ICP = intracranial pressure; iNPH = idiopathic normal pressure hydrocephalus; LIFT = lumbar infusion test; MMSE = Mini-Mental State Examination; mRS = modified Rankin Scale; OVM = overnight ICP monitoring; RAP = correlation coefficient between pulse amplitude and ICP; ROC = receiver operating characteristic; ROut = resistance to outflow of CSF; SLHS = Stein and Langfitt Hydrocephalus Score; VP = ventriculoperitoneal; ∆Kiefer = change in Kiefer score. obJeCtive The aim of the study was to analyze the diagnostic and predictive values of clinical tests, CSF dynamics, and intracranial pulsatility tests, compared with external lumbar drainage (ELD), for shunt response in patients with idiopathic normal pressure hydrocephalus (iNPH). Methods Sixty-eight consecutive patients with suspected iNPH were prospectively evaluated. Preoperative assessment included clinical tests, overnight intracranial pressure (ICP) monitoring, lumbar infusion test (LIFT), and ELD for 24-72 hours. Simple and multiple linear regression analyses were conducted to identify predictive parameters concerning the outcome after shunt therapy. results Positive response to ELD correctly predicted improvement after CSF diversion in 87.9% of the patients. A Mini-Mental State Examination (MMSE) value below 21 was associated with nonresponse after shunt insertion (specificity 93%, sensitivity 67%). Resistance to outflow of CSF (ROut) > 12 mm Hg/ml/min was false negative in 21% of patients. Intracranial pulsatility parameters yielded different results in various parameters (correlation coefficient between pulse amplitude and ICP, slow wave amplitude, and mean ICP) but did not correlate to outcome. In multiple linear regression analysis, a calculation of presurgical MMSE versus the value after ELD, ROut, and ICP amplitude quotient during LIFT was significantly associated with outcome (p = 0.04). CoNClusioNs Despite a multitude of invasive tests, presurgical cl...

Postextrasystolic acceleration of heart rate (HR), known as HR turbulence (HRT) is attenuated in patients with coronary artery disease at increased risk of adverse events. The influence of age and basic HR on HRT have not been evaluated in a large cohort of persons. In 95 healthy individuals, HRT onset (TO) and slope (TS) were calculated from 24-hour ambulatory electrocardiograms, as well as the turbulence timing (TT). Gender specific differences in TO and TS were compared in simple, linear, weighted regression model. The influence of age and the basic HR preceding ventricular premature contractions on HRT were examined. We found that, in men and women, TO decreases as basic HR increases (P < 0.01). In contrast, in men, TS decreased as basic HR increases, whereas in women, basic HR influenced TS only slightly (P < 0.01). A multiple, linear regression model revealed a decrease in HRT with increasing age in men. In conclusion, physiological acceleration of the HR within the first 11 beats after premature ventricular complex (VPC) was observed in >75% of healthy individuals. An accelerating HR preceding the VPC influenced HRT in men. An increasing age was associated with a decrease in HRT in men and a decrease in TO in women. These results illustrate the importance of physiological modulations of HRT when used for risk stratification, especially in older populations.

Site-specific genome modification (SSM) is an important tool for mosquito functional genomics and comparative gene expression studies, which contribute to a better understanding of mosquito biology and are thus a key to finding new strategies to eliminate vector-borne diseases. Moreover, it allows for the creation of advanced transgenic strains for vector control programs. SSM circumvents the drawbacks of transposon-mediated transgenesis, where random transgene integration into the host genome results in insertional mutagenesis and variable position effects. We applied the Cre/lox recombinase-mediated cassette exchange (RMCE) system to Aedes aegypti, the vector of dengue, chikungunya, and Zika viruses. In this context we created four target site lines for RMCE and evaluated their fitness costs. Cre-RMCE is functional in a two-step mechanism and with good efficiency in Ae. aegypti. The advantages of Cre-RMCE over existing site-specific modification systems for Ae. aegypti, phiC31-RMCE and CRISPR, originate in the preservation of the recombination sites, which 1) allows successive modifications and rapid expansion or adaptation of existing systems by repeated targeting of the same site; and 2) provides reversibility, thus allowing the excision of undesired sequences. Thereby, Cre-RMCE complements existing genomic modification tools, adding flexibility and versatility to vector genome targeting.

The production of recombinant proteins in bioreactors requires real-time process monitoring and control to increase process efficiency and to meet the requirements for a comprehensive audit trail. The combination of optical near-infrared turbidity sensors and dielectric spectroscopy provides diverse system information because different measurement principles are exploited. We used this combination of techniques to monitor and control the growth and protein production of stably transformed Drosophila melanogaster S2 cells expressing antimicrobial proteins. The in situ monitoring system was suitable in batch, fed-batch and perfusion modes, and was particularly useful for the online determination of cell concentration, specific growth rate (µ) and cell viability. These data were used to pinpoint the optimal timing of the key transitional events (induction and harvest) during batch and fed-batch cultivation, achieving a total protein yield of ~25 mg at the 1-L scale. During cultivation in perfusion mode, the OD880 signal was used to control the bleed line in order to maintain a constant cell concentration of 5 × 107 cells/mL, thus establishing a turbidostat/permittistat culture. With this setup, a five-fold increase in productivity was achieved and 130 mg of protein was recovered after 2 days of induced perfusion. Our results demonstrate that both sensors are suitable for advanced monitoring and integration into online control strategies.

Acceleration and deceleration of the heart rate after the occurrence of a ventricular premature complex is characterized as heart rate turbulence (HRT). Two parameters quantify heart rate turbulence: onset and slope. The physiological properties have not been clarified in a large cohort of persons yet. This study evaluated properties of HRT, and focused on the influence of basic heart rate and sex on HRT. Using a special protocol, 95 persons were studied prospectively. HRT and its physiological properties were determined in 95 persons using Holter ECGs. The authors found 24% with a turbulence onset 0% and 5% with a turbulence slope <2.5 ms/RRI. Mean heart rate during Holter differed significantly between women and men (745 vs 817 ms, P < 0.0001). A linear, weighted regression model revealed that an increased heart rate before a ventricular premature complex is associated with a decreased turbulence onset (P < 0.0001). Turbulence slope was attenuated by basic heart rate only in men (P = 0.0022). On the contrary, the study detected no influence of the basic heart rate on turbulence slope in women (P = 0.0015 for the comparison between women and men). Basic heart rate and sex show an influence on HRT and should be considered when using HRT for noninvasive risk stratification.

In cases of acute intoxication, honeybees often lay in front of their hives for several days, exposed to sunlight and weather, before a beekeeper can take a sample. Beekeepers send samples to analytical laboratories, but sometimes no residues can be detected. Temperature and sun light could influence the decrease of pesticides in bee samples and thereby residues left for analysis. Moreover, samples are usually sent via normal postal services without cooling. We investigated the temporal dynamics of whole-body residues of imidacloprid in live or dead honeybees following a single-meal dietary exposure of 41 ng/bee under various environmental conditions, such as freezing, exposure to UV light or transfer of individuals through the mail system. Immobile, “dead” looking honeybees recovered from paralysis after 48 hours. The decrease of residues in living but paralysed bees was stopped by freezing (= killing). UV light significantly reduced residues, but the mode of transport did not affect residue levels. Group feeding increased the variance of residues, which is relevant for acute oral toxicity tests. In conclusion, elapsed time after poisoning is key for detection of neonicotinoids. Freezing before mailing significantly reduced the decrease of imidacloprid residues and may increase the accuracy of laboratory analysis for pesticides.