Osteogenic differentiation of human mesenchymal stem cells on electroactive substrates.

This study investigates the effect of electroactivity and electrical charge distribution on the biological response of human bone marrow stem cells (hBMSCs) cultured in monolayer on flat poly(vinylidene fluoride), PVDF, substrates. Differences in cell behaviour, including proliferation, expression of multipotency markers CD90, CD105 and CD73, and expression of genes characteristic of different mesenchymal lineages, were observed both during expansion in basal medium before reaching confluence and in confluent cultures in osteogenic induction medium. The crystallisation of PVDF in the electrically neutral α-phase or in the electroactive phase ß, both unpoled and poled, has been found to have an important influence on the biological response. In addition, the presence of a permanent positive or negative surface electrical charge distribution in phase ß substrates has also shown a significant effect on cell behaviour.

Childhood social adversity and clustering of health risk behaviours during early adolescence in a population-based birth cohort.

OBJECTIVES: This study aimed to prospectively explore the association between early lifetime exposure to psychosocial adversity and engagement in health risk behaviours (HRBs) during early adolescence. STUDY DESIGN: This was a prospective study. METHODS: This study used data from the baseline (2005-2006), third (2016-2017) and fourth waves (2018-2020) of the Generation XXI birth cohort. Socio-economic circumstances (SECs) at baseline, adverse childhood experiences (ACEs; e.g. abuse, neglect, household dysfunction) at age 10 years and HRBs (i.e. alcohol consumption, smoking, physical exercise level, sedentary behaviours, sleep duration and eating behaviours) at age 13 years were measured. Patterns of HRBs were obtained using latent class analysis. Latent class regression analysis was used to estimate the likelihood of being engaged in HRBs according to the extent of exposure to ACEs (i.e. 0 ACEs, 1-3 ACEs, 4-5 ACEs and ≥6 ACEs) and negative family SECs. RESULTS: Adolescents whose mothers had a low level of education (adjusted odds ratio [aOR] = 2.72 [95% confidence interval {CI}, 2.33-3.18]), low occupational status (aOR = 3.21 [95% CI, 2.68-3.85]) and low income (aOR = 2.70 [95% CI, 2.23-3.28]) were more likely to be engaged in HRBs than their peers with higher SECs. Adolescents who experienced more ACEs were at a significantly increased risk of involvement in HRBs (aOR = 1.86 [95% CI, 1.33-2.63] for 4-5 ACEs vs aOR 2.41 [95% CI, 1.72-3.43] for ≥6 ACEs). No significant gender differences were observed. CONCLUSIONS: Adolescents from families with low SECs were more likely than their more affluent counterparts to be engaged in HRBs. Furthermore, more ACEs contributed to widening health inequalities.

Antibiotic use for respiratory tract infections among older adults living in long-term care facilities: a systematic review and meta-analysis.

BACKGROUND: Antibiotics are commonly prescribed for respiratory tract infections (RTIs) among older adults in long-term care facilities (LTCFs), and this contributes to the emergence of antimicrobial resistance. The objective of this study was to determine the antibiotic prescribing rate for RTIs among LTCF residents, and to analyse the antibiotic consumption patterns with the AwaRe monitoring tool, developed by the World Health Organization. METHODS: MEDLINE, EMBASE and CINAHL were searched from inception to March 2022. Original articles reporting antibiotic use for RTIs in LTCFs were included in this review. Study quality was assessed using the Joanna Briggs Institute's Critical Appraisal Checklist for Prevalence Data. A random-effects meta-analysis was employed to calculate the pooled estimates. Subgroup analysis was conducted by type of RTI, country, and study start year. RESULTS: In total, 47 articles consisting of 50 studies were included. The antibiotic prescribing rate ranged from 21.5% to 100% (pooled estimate 69.8%, 95% confidence interval 55.2-82.6%). The antibiotic prescribing rate for lower respiratory tract infections (LRTIs) was higher than the rates for viral and general RTIs. Compared with Italy, France and the USA, the Netherlands had lower antibiotic use for LRTIs. A proportion of viral RTIs were treated with antibiotics, and all the antibiotics were from the Watch group. Use of antibiotics in the Access group was higher in the Netherlands, Norway, Switzerland and Slovenia compared with the USA and Australia. CONCLUSION: The antibiotic prescribing rate for RTIs in LTCFs was high, and AWaRe antibiotic use patterns varied by type of RTI and country. Improving antibiotic use may require coordination efforts.

Ionic liquid-based electroactive materials: a novel approach for cardiac tissue engineering strategies.

Cardiac tissue regeneration strategies are increasingly taking advantage of electroactive scaffolds to actively recreate the tissue microenvironment. In this context, this work reports on advanced materials based on two different ionic liquids (ILs), 2-hydroxyethyl-trimethylammonium dihydrogen phosphate ([Ch][DHP]) and choline bis(trifluoromethylsulfonyl)imide ([Ch][TFSI]), combined with poly(vinylidene fluoride-co-trifluoroethylene) (P(VDF-TrFE)) for the development of ionic electroactive IL/polymer hybrid materials for cardiac tissue engineering (TE). The morphological, physico-chemical, thermal and electrical properties of the hybrid materials, as well as their potential use as scaffolds for cardiac TE applications, were evaluated. Besides inducing changes in surface topography, roughness and wettability of the composites, the incorporation of [Ch][DHP] and [Ch][TFSI] leads to the increase in surface (σsurface) and volume (σvolume) electrical conductivities. Furthermore, washing the hybrid samples with phosphate-buffered saline solution strongly decreases the σsurface, whereas σsurface and σvolume of the composites remain almost unaltered after exposure to ultraviolet sterilization treatment. Additionally, it is verified that the incorporation of IL influences the P(VDF-TrFE) microstructure and crystallization process, acting as a defect during its crystallization. Cytotoxicity assays revealed that hybrid films based on [Ch][DHP] alone are not cytotoxic. These films also support H9c2 myoblast cell adhesion and proliferation, demonstrating their suitability for cardiac TE strategies based on electroactive microenvironments.

Insomnia and nightmare profiles during the COVID-19 pandemic in Portugal: characterization and associated factors.

OBJECTIVE/BACKGROUND: To describe and characterize insomnia symptoms and nightmare profiles in Portugal during the first six weeks of a national lockdown due to COVID-19. PATIENTS/METHODS: An open cohort study was conducted to collect information of the general population during the first wave of SARS-CoV-2/COVID-19 pandemic in Portugal. We analyzed data from 5011 participants (≥16 years) who answered a weekly questionnaire about their well-being. Two questions about the frequency of insomnia and nightmares about COVID-19 were consecutively applied during six weeks (March-May 2020). Latent class analysis was conducted and different insomnia and nightmare profiles were identified. Associations between individual characteristics and both profiles were estimated using odds ratios (ORs) and 95% confidence intervals (CI). RESULTS: Five insomnia (No insomnia, Stable-mild, Decreasing-moderate, Stable-severe, Increasing-severe) and three nightmares profiles (Stable-mild, Stable-moderate, Stable-severe) were identified. Being female, younger, perceiving their income as insufficient and feelings of fear towards COVID-19 were associated with higher odds of insomnia (Women: OR = 6.98 95%CI: 4.18-11.64; ≥60 years: OR = 0.30 95%CI: 0.18-0.53; Insufficient income: adjusted OR (aOR) = 8.413 95%CI: 3.93-16.84; Often presenting fear of being infected with SARS-CoV-2 infection: aOR = 9.13 95%CI: 6.36-13.11), and nightmares (Women: OR = 2.60 95%CI: 1.74-3.86; ≥60 years: OR = 0.45 95%CI: 0.28-0.74; Insufficient income: aOR = 2.60 95%CI: 1.20-5.20; Often/almost always presenting fear of being infected with SARS-CoV-2 infection: aOR = 6.62 95%CI: 5.01-8.74). Having a diagnosis of SARS-CoV-2 virus infection was associated with worse patterns of nightmares about the pandemic. CONCLUSIONS: Social and psychological individual factors are important characteristics to consider in the development of therapeutic strategies to support people with sleep problems during the COVID-19 pandemic.

Training responsiveness of cardiorespiratory fitness and arterial stiffness following moderate-intensity continuous training and high-intensity interval training in adults with intellectual and developmental disabilities.

BACKGROUND: Cardiorespiratory fitness (CRF) prompts antiatherogenic adaptations in vascular function and structure. However, there is an extraordinary interindividual variability in response to a standard dose of exercise, wherein a substantial number of adults with intellectual and developmental disabilities (IDD) do not improve CRF. We (1) evaluated the effects of 12-month of moderate-intensity continuous training (MICT) on CRF and arterial stiffness and (2) tested whether an additional 3-month of high-intensity interval training (HIIT) would add to improvements in CRF responsiveness and arterial stiffness. METHODS: Fifteen adults with mild-to-moderate IDD (male adults = 9, 30.1 ± 7.5 years old) met 3 days per week for 30 min MICT for 12 months, after which the incidence of CRF responsiveness was calculated (≥5.0% change in absolute peak VO2 ). Thereafter, responders and non-responders started HIIT for 3 months with identical daily training load/frequency. Peak VO2 , local and regional indices of arterial stiffness were assessed prior to and after each period. RESULTS: Sixty per cent of the participants were non-responders following MICT, but the incidence dropped to 20% following HIIT (P = 0.03). Absolute peak VO2 values reached significant difference from pre-intervention (+0.38 ± 0.08 L min-1 , P = 0.001) only when HIIT was added. Lower limb pulse wave velocity (PWV) decreased following MICT (-0.8 ± 1.1 m s-1 , P = 0.049), whereas central PWV only decreased following HIIT (-0.8 ± 0.9 m s-1 , P = 0.013). CONCLUSIONS: Cardiorespiratory fitness responsiveness and reductions in PWV to a 12-month MICT period in adults with IDD improved following a period of HIIT programme inducing higher metabolic stress.

Enhanced ionic conductivity in poly(vinylidene fluoride) electrospun separator membranes blended with different ionic liquids for lithium ion batteries.

Electrospun poly(vinylidene fluoride) (PVDF) fiber membranes doped with different ionic liquids (ILs) and sharing the same anion were produced and their potential as separator membranes for battery applications was evaluated. Different types of ILs containing the same anion, bis(trifluoromethylsulfonyl)imide [TFSI]-, were used with IL concentrations ranging between 0 and 15 wt% The morphology, microstructure, thermal and electrical properties (ionic conductivity and electrochemical window) of the membranes were evaluated. The presence of ILs in the PVDF polymer matrix influences the fiber diameter and the content of the polar ß phase within the polymer, as well as the degree of crystallinity. The thermal stability of the membranes decreases with the incorporation of IL. Impedance spectroscopy tests show a maximum ionic conductivity of 2.8 mS.cm-1 for 15% of 1-ethyl-3-methylimidazolium bis(trifluoromethylsulfonyl)imide ([Emim][TFSI]) at room temperature. The electrochemical stability of the samples ranges from 0.0 to 6.0 V. When evaluated as battery separator membranes in C-LiFePO4 half-cells, a maximum discharge capacity of 119 mAh.g-1 at C-rate was obtained for the PVDF membrane with 15% [Emim][TFSI], with a coulombic efficiency close to 100%. The results demonstrate that the produced electrospun membranes are suitable for applications as separators for lithium ion batteries (LIBs).

Poly(vinylidene) fluoride membranes coated by heparin/collagen layer-by-layer, smart biomimetic approaches for mesenchymal stem cell culture.

The use of piezoelectric materials in tissue engineering has grown considerably since inherent bone piezoelectricity was discovered. Combinations of piezoelectric polymers with magnetostrictive nanoparticles (MNP) can be used to magnetoelectrically stimulate cells by applying an external magnetic field which deforms the magnetostrictive nanoparticles in the polymer matrix, deforming the polymer itself, which varies the surface charge due to the piezoelectric effect. Poly(vinylidene) fluoride (PVDF) is the piezoelectric polymer with the largest piezoelectric coefficients, being a perfect candidate for osteogenic differentiation. As a first approach, in this paper, we propose PVDF membranes containing magnetostrictive nanoparticles and a biomimetic heparin/collagen layer-by-layer (LbL) coating for mesenchymal stem cell culture. PVDF membranes 20% (w/v) with and without cobalt ferrite oxide (PVDF-CFO) 10% (w/w) were produced by non-solvent induced phase separation (NIPS). These membranes were found to be asymmetric, with a smooth surface, crystallinity ranging from 65% to 61%, and an electroactive ß-phase content of 51.8% and 55.6% for PVDF and PVDF-CFO, respectively. Amine groups were grafted onto the membrane surface by an alkali treatment, confirmed by ninhydrin test and X-ray photoelectron spectroscopy (XPS), providing positive charges for the assembly of heparin/collagen layers by the LbL technique. Five layers of each polyelectrolyte were deposited, ending with collagen. Human mesenchymal stem cells (hMSC) were used to test cell response in a short-term culture (1, 3 and 7 days). Nucleus cell counting showed that LbL favored cell proliferation in PVDF-CFO over non-coated membranes.

Polymer-based actuators: back to the future.

Polymer-based actuators play a key role in the area of smart materials and devices, and for this reason different polymer-based actuators have appeared in recent years and are implemented in a broad range of fields, including biomedical, optical or electronics, among others. Although it is possible to find more types, they are mainly classified into two main groups according to their different working principles: electromechanical - with electrical to mechanical energy conversion - and magnetomechanical - with magnetic to mechanical energy conversion. The present work provides a comprehensive and critical review of the recent studies in this field. The operating principles, some representative designs, performance analyses and practical applications will be presented. The future development perspectives of this interesting field will be also discussed. Thus, the present work provides a comprehensive understanding of the effects reported in the past, introduces solutions to the present limitations and, back to the future, serves as a useful guidance for the design of new polymer-based actuators aiming to improve their output performances.

Intermittent binge-like ethanol exposure during adolescence attenuates the febrile response by reducing brown adipose tissue thermogenesis in rats.

Ethanol (EtOH) consumption is a primary health risk worldwide, which generally starts during adolescence in a binge pattern (i.e., the episodic consumption of high amounts). Binge EtOH consumption can lead to modifications of the innate and adaptive immune responses, including fever. The present study evaluated the febrile response that was induced by lipopolysaccharide (LPS) and prostaglandins E2 (PGE2) and the mechanisms of thermoregulation in adolescent rats that were exposed to EtOH in a binge-like pattern. Male Wistar rats were treated with an intraperitoneal (i.p.) injection of EtOH or saline on postnatal days (PND) 25, 26, 29, 30, 33, 34, 37, and 38. On PND 51, they received a pyrogenic challenge with LPS (i.p.) or PGE2 (intracerebroventricular) to induce a febrile response. Interscapular brown adipose tissue (BAT) mass and uncoupling protein (UCP) activity in isolated mitochondria were evaluated on PND 51. The rats were then subjected to cold challenges to analyze adaptive thermogenesis. Intermittent EtOH exposure during adolescence impaired the LPS- and PGE2-induced febrile response 12 days after the end of EtOH exposure. Ethanol exposure decreased interscapular BAT mass, oxygen consumption, and UCP activity in isolated mitochondria, resulting in an impairment in thermogenesis at 5 °C. No morphological changes in BAT were observed. These findings indicate that binge-like EtOH exposure during adolescence impairs thermoregulation by reducing BAT mass and function. This reduction may last for a prolonged period of time after the cessation of EtOH exposure and may affect both cold defenses and the febrile response during the development of infectious diseases.

Renewing Felsenstein's phylogenetic bootstrap in the era of big data.

Felsenstein's application of the bootstrap method to evolutionary trees is one of the most cited scientific papers of all time. The bootstrap method, which is based on resampling and replications, is used extensively to assess the robustness of phylogenetic inferences. However, increasing numbers of sequences are now available for a wide variety of species, and phylogenies based on hundreds or thousands of taxa are becoming routine. With phylogenies of this size Felsenstein's bootstrap tends to yield very low supports, especially on deep branches. Here we propose a new version of the phylogenetic bootstrap in which the presence of inferred branches in replications is measured using a gradual 'transfer' distance rather than the binary presence or absence index used in Felsenstein's original version. The resulting supports are higher and do not induce falsely supported branches. The application of our method to large mammal, HIV and simulated datasets reveals their phylogenetic signals, whereas Felsenstein's bootstrap fails to do so.

Human Mesenchymal Stem Cells Growth and Osteogenic Differentiation on Piezoelectric Poly(vinylidene fluoride) Microsphere Substrates.

The aim of this work was to determine the influence of the biomaterial environment on human mesenchymal stem cell (hMSC) fate when cultured in supports with varying topography. Poly(vinylidene fluoride) (PVDF) culture supports were prepared with structures ranging between 2D and 3D, based on PVDF films on which PVDF microspheres were deposited with varying surface density. Maintenance of multipotentiality when cultured in expansion medium was studied by flow cytometry monitoring the expression of characteristic hMSCs markers, and revealed that cells were losing their characteristic surface markers on these supports. Cell morphology was assessed by scanning electron microscopy (SEM). Alkaline phosphatase activity was also assessed after seven days of culture on expansion medium. On the other hand, osteoblastic differentiation was monitored while culturing in osteogenic medium after cells reached confluence. Osteocalcin immunocytochemistry and alizarin red assays were performed. We show that flow cytometry is a suitable technique for the study of the differentiation of hMSC seeded onto biomaterials, giving a quantitative reliable analysis of hMSC-associated markers. We also show that electrosprayed piezoelectric poly(vinylidene fluoride) is a suitable support for tissue engineering purposes, as hMSCs can proliferate, be viable and undergo osteogenic differentiation when chemically stimulated.

Kinetic study of thermal degradation of chitosan as a function of deacetylation degree.

Thermal degradation of chitosan with varying deacetylation degree (DD) ranging between 50 and 85% was analyzed by dynamic thermogravimetric analysis at different heating rates. The present study focused on the temperature range between 500 and 800K, above water evaporation. Thermal degradation showed a main degradation stage in this temperature interval with a second stage that appeared in the weight derivative curves as a shoulder in the high temperature side of the main peak with increasing intensity as the DD decreased. The Kissinger and isoconversional Ozawa-Flynn-Wall models were employed to evaluate the Ea of both thermal degradation processes. Different kinetic models were tested to computer simulate the thermogravimetric traces calculating the model parameters with a non-linear least squares fitting routine. The Sestack-Berggren model allowed reproducing accurately the overlapping of the two degradation mechanisms and calculating the mass fraction lost in each of them revealing the coupling between the two degradation mechanisms.

3D map distribution of metallic nanoparticles in whole cells using MeV ion microscopy.

In this work, a new tool was developed, the MORIA program that readily translates Rutherford backscattering spectrometry (RBS) output data into visual information, creating a display of the distribution of elements in a true three-dimensional (3D) environment. The program methodology is illustrated with the analysis of yeast Saccharomyces cerevisiae cells, exposed to copper oxide nanoparticles (CuO-NP) and HeLa cells in the presence of gold nanoparticles (Au-NP), using different beam species, energies and nuclear microscopy systems. Results demonstrate that for both cell types, the NP internalization can be clearly perceived. The 3D models of the distribution of CuO-NP in S. cerevisiae cells indicate the nonuniform distribution of NP in the cellular environment and a relevant confinement of CuO-NP to the cell wall. This suggests the impenetrability of certain cellular organelles or compartments for NP. By contrast, using a high-resolution ion beam system, discretized agglomerates of Au-NP were visualized inside the HeLa cell. This is consistent with the mechanism of entry of these NPs in the cellular space by endocytosis enclosed in endosomal vesicles. This approach shows RBS to be a powerful imaging technique assigning to nuclear microscopy unparalleled potential to assess nanoparticle distribution inside the cellular volume.

Processing and size range separation of pristine and magnetic poly(l-lactic acid) based microspheres for biomedical applications.

Biodegradable poly(l-lactic acid) (PLLA) and PLLA/CoFe2O4 magnetic microspheres with average sizes ranging between 0.16-3.9µm and 0.8-2.2µm, respectively, were obtained by an oil-in-water emulsion method using poly(vinyl alcohol) (PVA) solution as the emulsifier agent. The separation of the microspheres in different size ranges was then performed by centrifugation and the colloidal stability assessed at different pH values. Neat PLLA spheres are more stable in alkaline environments when compared to magnetic microspheres, both types being stable for pHs higher than 4, resulting in a colloidal suspension. On the other hand, in acidic environments the microspheres tend to form aggregates. The neat PLLA microspheres show a degree of crystallinity of 40% whereas the composite ones are nearly amorphous (17%). Finally, the biocompatibility was assessed by cell viability studies with MC3T3-E1 pre-osteoblast cells.

Central and peripheral fat body mass have a protective effect on osteopenia or osteoporosis in adults and elderly?

UNLABELLED: This cross-sectional study involves randomly selected men aged 50 to 99 years and postmenopausal women. Either central fat mass or peripheral fat mass were associated to osteoporosis or osteopenia independently from fat-free body mass and other confounding factors. INTRODUCTION: Obesity and osteoporosis are public health problems that probably share common pathophysiological mechanisms. The question if body fat mass, central or peripheral, is protective or harmful for osteoporosis or osteopenia is not completely resolved. This study aims to investigate the association between osteoporosis or osteopenia, and fat body mass (central and peripheral) independently from fat-free body mass, in men aged 50 to 99 years old and postmenopausal women randomly selected in the community. METHODS: This is a cross-sectional investigation with a random sample of registered population in Niterói Family Doctor Program (FDP), State of Rio de Janeiro, Brazil. Bone mineral density (BMD) and fat-free mass were assessed by dual X-ray absorptiometry (DXA). RESULTS: There was statistically significant bivariate association between bone loss with gender, age, skin color, alcohol consumption at risk dose, use of thiazide, fat-free body mass, and fat body mass (central and peripheral). In the multiple analysis of fat-free body mass, central and peripheral fat body mass showed an independent and protective effect on the presence of osteoporosis or osteopenia (p value <0.001). CONCLUSION: Since both obesity and osteoporosis are public health problems worldwide, strategies aimed at preventing both conditions should be encouraged during aging.

Anxiety and depression symptoms in hepatic encephalopathy: are they psychiatric or organic?

BACKGROUND: Hepatic encephalopathy (HE) represents a broad continuum of neuropsychiatric abnormalities, from subtly altered mental status to deep coma, seen in patients with liver dysfunction. HE can mimic all of the major psychiatric syndromes. The distinction between HE and a psychiatric condition, namely depression, is sometimes difficult. Some liver patients end up being medicated with psychiatric drugs which might worsen their medical state. The main objective of this study was to try to find the correlations between anxiety and depression symptoms and the presence of HE to better diagnose and treat these patients. METHODS: Sixty consecutive liver transplant candidates, attending the outpatient clinics of a liver transplantation center were studied from January 1, 2012, to December 1, 2012. Each patient was assessed by means of Psychometric Hepatic Encephalopathy Score subtests and Hospital Anxiety and Depression Scale. RESULTS: We found a statistically significant relationship between HE and some of the depressive symptoms: anhedonia and loss of energy. CONCLUSIONS: These findings may indicate that when in the presence of an HE patient with depressive symptoms, HE-directed therapies should be attempted before antidepressant drugs.

Role of Angiotensin II type 1 receptor on renal NAD(P)H oxidase, oxidative stress and inflammation in nitric oxide inhibition induced-hypertension.

AIMS: Activation of the renin-angiotensin system (RAS), renal oxidative stress and inflammation are constantly present in experimental hypertension. Nitric oxide (NO) inhibition with N(w)-nitro-L-arginine methyl ester (L-NAME) has previously been reported to produce hypertension, increased expression of Angiotensin II (Ang II) and renal dysfunction. The use of Losartan, an Ang II type 1 receptor (AT1R) antagonist has proven to be effective reducing hypertension and renal damage; however, the mechanism by which AT1R blockade reduced kidney injury and normalizes blood pressure in this experimental model is still complete unknown. The current study was designed to test the hypothesis that AT1R activation promotes renal NAD(P)H oxidase up-regulation, oxidative stress and cytokine production during L-NAME induced-hypertension. MAIN METHODS: Male Sprague-Dawley rats were distributed in three groups: L-NAME, receiving 70 mg/100ml of L-NAME, L-NAME+Los, receiving 70 mg/100ml of L-NAME and 40 mg/kg/day of Losartan; and Controls, receiving water instead of L-NAME or L-NAME and Losartan. KEY FINDINGS: After two weeks, L-NAME induced high blood pressure, renal overexpression of AT1R, NAD(P)H oxidase sub-units gp91, p22 and p47, increased levels of oxidative stress, interleukin-6 (IL-6) and interleukin-17 (IL-17). Also, we found increased renal accumulation of lymphocytes and macrophages. Losartan treatment abolished the renal expression of gp91, p22, p47, oxidative stress and reduced NF-κB activation and IL-6 expression. SIGNIFICANCE: These findings indicate that NO induced-hypertension is associated with up-regulation of NADPH oxidase, oxidative stress production and overexpression of key inflammatory mediators. These events are associated with up-regulation of AT1R, as evidenced by their reversal with AT1R blocker treatment.

Genetic diversity of spineless Cereus jamacaru accessions using morphological and molecular markers.

This is the first study to examine the genetic diversity of mandacaru cactus (Cereus jamacaru P. DC.). Plants of spineless mandacaru are commonly found in gardens and parks of urban areas in northeastern Brazil. In addition to exploring their ornamental potential, morphological, and genetic characterization may contribute to the development of plant materials that can be used as a source of macromolecules of potential economic interest. The goal of this study was to estimate the genetic variability of spineless mandacaru accessions using random amplified polymorphic DNA (RAPD) and inter-simple sequence repeat (ISSR) molecular markers, and to characterize their morphology. Ten samples of newly emitted shoots with differentiated areolas and ribs were collected from each accession from the Cactaceous Germplasm Collection of Embrapa Agroindústria Tropical, in Fortaleza, CE. Shoot shape and aspects of spine primordia (presence, location, grouping, and size of spines) were evaluated. The morphological analysis showed that the spineless mandacaru presented spine primordia. Twenty-six RAPD and 15 ISSR primers were polymorphic. A total of 262 markers were obtained, 129 of which were polymorphic. The average polymorphism of ISSR markers was higher than that of RAPD markers. The dendrograms for both analyses showed differentiation between accessions. Nevertheless, the molecular markers detected higher levels of diversity and a different pattern of diversity than those found using morphological markers. The molecular results revealed significant genetic variability both within and between groups.

A possible role of a cerebral energy gene in alcoholism.

We examined a possible relationship between genes responsible for energy metabolism of the brain and addictive behavior in an animal model. We used non-inbred, Swiss mice exposed to a three-bottle free-choice model [water, 5% (v/v) ethanol, and 10% (v/v) ethanol] over a 16-week period, consisting of four phases: acquisition, withdrawal, reexposure, and quinine-adulteration. The mice were then behaviorally classified into three groups: loss-of-control-drinker (preference for ethanol and high levels of consumption during all phases, N = 6), heavy-drinker (preference for ethanol and high levels of consumption during acquisition and reduction during quinine-adulteration, N = 7), and light-drinker (preference for water during all phases, N = 10). Another group only received tap water (ethanol-naive control mice, N = 9). Further analysis using quantitative real-time PCR showed that in mice behaviorally classified as loss-of-control-drinkers, there was a significant inverse correlation between transcript levels of the Hadh gene and those of other energy metabolism genes in the nucleus of the amygdala, suggesting that this pathway may contribute to ethanol consumption in these mice. We conclude that cerebral energy metabolism is involved with ethanol addiction, meriting further study.