The choroid plexus transcriptome reveals changes in type I and II interferon responses in a mouse model of Alzheimer's disease

Alzheimer's disease (AD) is a neurodegenerative disorder characterized by a marked decline in cognition and memory function. Increasing evidence highlights the essential role of neuroinflammatory and immune-related molecules, including those produced at the brain barriers, on brain immune surveillance, cellular dysfunction and amyloid beta (Aß) pathology in AD. Therefore, understanding the response at the brain barriers may unravel novel pathways of relevance for the pathophysiology of AD. Herein, we focused on the study of the choroid plexus (CP), which constitutes the blood-cerebrospinal fluid barrier, in aging and in AD. Specifically, we used the PDGFB-APPSwInd (J20) transgenic mouse model of AD, which presents early memory decline and progressive Aß accumulation, and littermate age-matched wild-type (WT) mice, to characterize the CP transcriptome at 3, 5-6 and 11-12months of age. The most striking observation was that the CP of J20 mice displayed an overall overexpression of type I interferon (IFN) response genes at all ages. Moreover, J20 mice presented a high expression of type II IFN genes in the CP at 3months, which became lower than WT at 5-6 and 11-12months. Importantly, along with a marked memory impairment and increased glial activation, J20 mice also presented a similar overexpression of type I IFN genes in the dorsal hippocampus at 3months. Altogether, these findings provide new insights on a possible interplay between type I and II IFN responses in AD and point to IFNs as targets for modulation in cognitive decline.

An efficient chronic unpredictable stress protocol to induce stress-related responses in C57BL/6 mice

Exposure to chronic stress can have broad effects on health ranging from increased predisposition for neuropsychiatric disorders to deregulation of immune responses. The chronic unpredictable stress (CUS) protocol has been widely used to study the impact of stress exposure in several animal models and consists in the random, intermittent, and unpredictable exposure to a variety of stressors during several weeks. CUS has consistently been shown to induce behavioral and immunological alterations typical of the chronic stress-response. Unfortunately C57BL/6 mice, one of the most widely used mouse strains, due to the great variety of genetically modified lines, seem to be resistant to the commonly used 4-week-long CUS protocol. The definition of an alternative CUS protocol allowing the use of C57BL/6 mice in chronic stress experiments is a need. Here, we show that by extending the CUS protocol to 8?weeks is possible to induce a chronic stress-response in C57BL/6 mice, as revealed by abrogated body weight gain, increased adrenals weight, and an overactive hypothalamic-pituitary-adrenal axis with increased levels of serum corticosterone. Moreover, we also observed stress-associated behavioral alterations, including the potentiation of anxious-like and depressive-like behaviors and a reduction of exploratory behavior, as well as subtle stress-related changes in the cell population of the thymus and of the spleen. The present protocol for C57BL/6 mice consistently triggers the spectrum of CUS-induced changes observed in rats and, thus, will be highly useful to researchers that need to use this particular mouse strain as an animal model of neuropsychiatric disorders and/or immune deregulation related to CUS.

Implementation and validation of a strain rate dependent anisotropic continuum model for masonry

A newly developed strain rate dependent anisotropic continuum model is proposed for impact and blast applications in masonry. The present model adopted the usual approach of considering different yield criteria in tension and compression. The analysis of unreinforced block work masonry walls subjected to impact is carried out to validate the capability of the model. Comparison of the numerical predictions and test data revealed good agreement. Next, a parametric study is conducted to evaluate the influence of the tensile strengths along the three orthogonal directions and of the wall thickness on the global behavior of masonry walls.

Dynamic interface model for masonry walls subjected to high strain rate out-of-plane loads

The present study proposes a dynamic constitutive material interface model that includes non-associated flow rule and high strain rate effects, implemented in the finite element code ABAQUS as a user subroutine. First, the model capability is validated with numerical simulations of unreinforced block work masonry walls subjected to low velocity impact. The results obtained are compared with field test data and good agreement is found. Subsequently, a comprehensive parametric analysis is accomplished with different joint tensile strengths and cohesion, and wall thickness to evaluate the effect of the parameter variations on the impact response of masonry walls.

Hematological responses of tambaqui Colossoma macropomum (Serrassalmidae) fed with diets supplemented with essential oil from Mentha piperita (Lamiaceae) and challenged with Aeromonas hydrophila

ABSTRACTIn fish farmings, diseases can be reduced by using immunostimulants. The aim of this study was to evaluate the immunostimulant potential of Mentha piperita in tambaqui fed with 0, 0.5, 1.0 and 1.5% of oil per kg of commercial fish feed. The fish were inoculated with Aeromonas hydrophila to challenge them. Hematological and biochemical parameters were determined after 30 days of feeding and seven days after the challenge. There was no mortality and M. piperita oil did not influence fish production parameters. However, blood hemoglobin concentration (Hb) increased in the fish fed with 0.5 and 1.5% of oil per kg of diet; albumin increased in those fed with 1.0%; cholesterol increased in all groups with oil; and triglycerides increased in those fed with 0.5%. After the bacterial challenge, the fish showed decreases in Hb when fed with diet enriched with 1.5% oil per kg of diet, in mean corpuscular volume with 1.0% and in mean corpuscular hemoglobin concentration with 0 and 1.5%. Protein levels increased in groups with 0 and 1.5% of oil and albumin when fed with 0 and 1.0%; cholesterol levels increased in the control group; and high levels of triglycerides were observed in the groups with 0, 0.5 and 1.5%. Thus, M. piperita essential oil promoted hematological alterations in tambaqui and can be recommended in diets containing up to 1.0% per kg, because of the minimal physiological modifications caused. However, additional studies are necessary to obtain more information regarding to the physiological effects of this immunostimulant.

Thin films composed of Ag nanoclusters dispersed in TiO2: Influence of composition and thermal annealing on the microstructure and physical responses

Noble metal powders containing gold and silver have been used for many centuries, providing different colours in the windows of the medieval cathedrals and in ancient Roman glasses. Nowadays, the interest in nanocomposite materials containing noble nanoparticles embedded in dielectric matrices is related with their potential use for a wide range of advanced technological applications. They have been proposed for environmental and biological sensing, tailoring colour of functional coatings, or for surface enhanced Raman spectroscopy. Most of these applications rely on the so-called localised surface plasmon resonance absorption, which is governed by the type of the noble metal nanoparticles, their distribution, size and shape and as well as of the dielectric characteristics of the host matrix. The aim of this work is to study the influence of the composition and thermal annealing on the morphological and structural changes of thin films composed of Ag metal clusters embedded in a dielectric TiO2 matrix. Since changes in size, shape and distribution of the clusters are fundamental parameters for tailoring the properties of plasmonic materials, a set of films with different Ag concentrations was prepared. The optical properties and the thermal behaviour of the films were correlated with the structural and morphological changes promoted by annealing. The films were deposited by DC magnetron sputtering and in order to promote the clustering of the Ag nanoparticles the as-deposited samples were subjected to an in-air annealing protocol. It was demonstrated that the clustering of metallic Ag affects the optical response spectrum and the thermal behaviour of the films.

Chitosan-based scaffolds for tissue regeneration: preparation and microstructure characterization

Scaffolds are porous three-dimensional supports, designed to mimic the extracellular environment and remain temporarily integrated into the host tissue while stimulating, at the molecular level, specific cellular responses to each type of body tissues. The major goal of the research work entertained herein was to study the microstructure of scaffolds made from chitosan (Ch), blends of chitosan and sodium alginate (Ch/NaAlg), blends of chitosan, sodium alginate and calcium chloride (Ch/NaAlg/CaCl2) and blends of chitosan, sodium alginate and hydroxyapatite (Ch/NaAlg/HA). Scaffolds possessing ideal physicochemical properties facilitate cell proliferation and greatly increase the rate of recovery of a damaged organ tissue. Using CT three-dimensional images of the scaffolds, it was observed that all scaffolds had a porosity in the range 64%-92%, a radius of maximum pore occurrence in the range 95m-260m and a permeability in the range 1×10-10-18×10-10 m2. From the results obtained, the scaffolds based on Ch, Ch/NaAlg and Ch/NaAlg/CaCl2 would be most appropriate both for the growth of osteoid and for bone tissue regeneration, while the scaffold made with a blend of Ch/NaAlg/HA, by possessing larger pores size, might be used as a support for fibrovascular tissue.

Flexible gastrointestinal motility pressure sensors based on aluminum thin-film strain-gauge arrays

This paper reports on an innovative approach to measuring intraluminal pressure in the upper gastrointestinal (GI) tract, especially monitoring GI motility and peristaltic movements. The proposed approach relies on thin-film aluminum strain gauges deposited on top of a Kapton membrane, which in turn lies on top of an SU-8 diaphragm-like structure. This structure enables the Kapton membrane to bend when pressure is applied, thereby affecting the strain gauges and effectively changing their electrical resistance. The sensor, with an area of 3.4 mm2, is fabricated using photolithography and standard microfabrication techniques (wet etching). It features a linear response (R2 = 0.9987) and an overall sensitivity of 2.6 mV mmHg−1. Additionally, its topology allows a high integration capability. The strain gauges’ responses to pressure were studied and the fabrication process optimized to achieve high sensitivity, linearity, and reproducibility. The sequential acquisition of the different signals is carried out by a microcontroller, with a 10-bit ADC and a sample rate of 250 Hz. The pressure signals are then presented in a user-friendly interface, developed using the Integrated Development Environment software, QtCreator IDE, for better visualization by physicians.

Evaluation of the heart rate and arrhythmias following the Maze procedure for chronic atrial fibrillation

PURPOSE: To assess the presence and the prevalence of arrhythmias and the variability of the heart rate in the medium-term postoperative period following the maze procedure for chronic atrial fibrillation (AF). METHODS: Seventeen patients with a mean age of 51.7±12.9 years, who previously underwent the maze procedure without cryoablation for chronic atrial fibrillation, were evaluated with the 24 hour electrocardiogram (ECG) - Holter monitoring from the 6th month after the operation. Valvular and coronary procedures were concomitantly performed. RESULTS: The mean heart rate during Holter monitoring was 82±8bpm; the maximal heart rate was 126 ± 23bpm and the minimal heart rate 57±7bpm. Sinus rhythm was found in 10 (59%) patients and atrial rhythm was found in 7 (41%). Supraventricular extrasystoles had a rate of 2.3±5.5% of the total number of heartbeats and occurred in 16 (94%) patients. Six (35%) patients showed nonsustained atrial tachycardia. Ventricular extrasystoles, with a rate of 0.8±0.5% of the total heartbeats, occurred in 14 (82%) patients. The chronotropic competence was normal in 9 (53%) patients and attenuated in 8 (47%). The atrioventricular conduction (AV) was unchanged in 13 (76%) patients and there were 4 (24%) cases of first degree atrioventricular block (AVB). CONCLUSION: After the maze procedure, the values for the mean heart rate, AV conduction and chronotropic competence approach the normal range, although some cases show attenuation of the chronotropic response, first degree AV block or benign arrhythmias.

Beta-adrenergic blocking agents in heart failure

Cardiac dysfunction in heart failure is widely recognized as a progressive process, regardless of the clinical signs and symptoms. An increase in cardiac sympathetic drive is one of the earliest neurohormonal responses occurring in patients with heart failure and may be one of the major causes of the progressive remodeling leading to the decline in myocardial function, and responsible for the poor prognosis of patients with heart failure. Therefore, recent data provided by several appropriately designed clinical trials clearly indicate the benefits of beta-adrenoceptor blocking agents, combined with diuretics, ACE inhibitors, and digoxin in chronic heart failure class II to IV due to systolic ventricular dysfunction. The benefits are related to symptoms, functional capacity, remodeling, and improvement in left ventricular function, reduction in cardiovascular hospitalization, a decrease in the overall and sudden cardiac death rate, and are similar in patients with ischemic or nonischemic cardiomyopathy, independent of age, gender, or functional class. In this review we describe the cardiovascular effects of the increase in sympathetic drive, the pharmacological properties of the beta-blockers most evaluated in heart failure therapy (metoprolol, bisoprolol, and carvedilol), the major clinical trials related to these agents in heart failure, the recommendations for their appropriate use in clinical practice, the precautions to be adopted, and how to handle the more common adverse reactions.

Sex differences in the fetal heart rate variability indices of twins

Aims: To evaluate the differences in linear and complex heart rate dynamics in twin pairs according to fetal sex combination [male-female (MF), male-male (MM), and female-female (FF)]. Methods: Fourteen twin pairs (6 MF, 3 MM, and 5 FF) were monitored between 31 and 36.4 weeks of gestation. Twenty-six fetal heart rate (FHR) recordings of both twins were simultaneously acquired and analyzed with a system for computerized analysis of cardiotocograms. Linear and nonlinear FHR indices were calculated. Results: Overall, MM twins presented higher intrapair average in linear indices than the other pairs, whereas FF twins showed higher sympathetic-vagal balance. MF twins exhibited higher intrapair average in entropy indices and MM twins presented lower entropy values than FF twins considering the (automatically selected) threshold rLu. MM twin pairs showed higher intrapair differences in linear heart rate indices than MF and FF twins, whereas FF twins exhibited lower intrapair differences in entropy indices. Conclusions: The results of this exploratory study suggest that twins have sex-specific differences in linear and nonlinear indices of FHR. MM twins expressed signs of a more active autonomic nervous system and MF twins showed the most active complexity control system. These results suggest that fetal sex combination should be taken into consideration when performing detailed evaluation of the FHR in twins.

Diagnostic value of the tilt-table test for the assessment of syncope in children and adolescents

OBJECTIVE - To assess the diagnostic value, the characteristics, and feasibility of tilt-table testing in children and adolescents. METHODS - From August 1991 to June 1997, we retrospectively assessed 94 patients under the age of 18 years who had a history of recurring syncope and presyncope of unknown origin and who were referred for tilt-table testing. These patients were divided into 2 groups: group I (children) - 36 patients with ages ranging from 3 to 12 (mean of 9.19±2.31) years; group II (adolescents) - 58 patients with ages ranging from 13 to 18 (mean of 16.05±1.40) years. We compared the positivity rate, the type of hemodynamic response, and the time period required for the test to become positive in the 2 groups. RESULTS - The positivity rates were 41.6 % and 50% for groups I and II, respectively. The pattern of positive hemodynamic response that predominated in both groups was the mixed response. The mean time period required for the test to become positive was shorter in group I (11.0±7.23 min) than in group II (18.44±7.83 min). No patient experienced technical difficulty or complications. CONCLUSION - No difference was observed in regard to feasibility, positivity rate, and pattern of positive response for the tilt-table test in children and adolescents. Pediatric patients had earlier positive responses.

Fetal behavior and heart rate in twin pregnancy: a review

Fetal movements and fetal heart rate (FHR) are well-established markers of fetal well-being and maturation of the fetal central nervous system. The purpose of this paper is to review and discuss the available knowledge on fetal movements and heart rate patterns in twin pregnancies. There is some evidence for an association or similarity in fetal movement incidences or FHR patterns between both members of twin pairs. However, the temporal occurrence of these patterns seems to be for the most part asynchronous, especially when stricter criteria are used to define synchrony. The available data suggest that fetal behavior is largely independent of sex combination, fetal position, and presentation. Conversely, chorionicity appears to have some influence on fetal behavior, mainly before 30 weeks of gestation. There is preliminary evidence for the continuity of inter-individual differences in fetal activity and FHR patterns over pregnancy. Comparisons between studies are limited by large methodological differences and absence of uniform concepts and definitions. Future studies with high methodological quality are needed to provide a more comprehensive knowledge of normal fetal behavior in twin pregnancy.

Influence of angiotensin II receptor subtypes of the paraventricular nucleus on the physiological responses induced by angiotensin II injection into the medial septal area

OBJECTIVE: We determined the effects of losartan and PD 123319 (antagonists of the AT1 and AT2 angiotensin receptors, respectively), and [Sar¹, Ala8] ANG II (a relatively peptide antagonist of angiotensin receptors) injected into the paraventricular nucleus (PVN) on water and 3% NaCl intake, and the diuretic, natriuretic, and pressor effects induced by administration of angiotensin II (ANG II) into the medial septal area (MSA) of conscious rats. METHODS: Holtzman rats were used . Animals were anesthetized with tribromoethanol (20 mg) per 100 grams of body weight, ip. A stainless steel guide cannula was implanted into the MSA and PVN. All drugs were injected in 0.5-mul volumes for 10-15 seconds. Seven days after brain surgery, water and 3% NaCl intake, urine and sodium excretion, and arterial blood pressure were measured. RESULTS: Losartan (40 nmol) and [Sar¹, Ala8] ANG II (40 nmol) completely eliminated whereas PD 123319 (40 nmol) partially blocked the increase in water and sodium intake and the increase in arterial blood pressure induced by ANG II (10 nmol) injected into the MSA. The PVN administration of PD 123319 and [Sar¹, Ala8] ANG II blocked whereas losartan attenuated the diuresis and natriuresis induced by MSA administration of ANG II. CONCLUSION: MSA involvement with PVN on water and sodium homeostasis and arterial pressure modulation utilizing ANGII receptors is suggested.