Improved Metal Cation Optosensing Membranes through the Incorporation of Sulphated Polysaccharides.

Optosensing chitosan-based membranes have been applied for the detection of heavy metals, especially in drinking water. The novelty of this study is based on the use of sulphated polysaccharides, in such optosensing membranes, aiming at an improved analytical performance. The sulphated polysaccharides, such as ulvan, fucoidan and chondroitin sulfate, were extracted from by-products and wastes of marine-related activities. The membranes were developed for the analysis of aluminum. The variation in the visible absorbance of the sensor membranes after the contact between the chromophore and the aluminum cation was studied. The membranes containing sulphated polysaccharides showed improved signals when compared to the chitosan-only membrane. As for the detection limits for the membranes containing ulvan, fucoidan and chondroitin sulfate, 0.17 mg L-1, 0.21 mg L-1 and 0.36 mg L-1 were obtained, respectively. The values were much lower than that obtained for the chitosan-only membrane, 0.52 mg L-1, which shows the improvement obtained from the sulphated polysaccharides. The results were obtained with the presence of CTAB in analysis solution, which forms a ternary complex with the aluminum cation and the chromophore. This resulted in an hyperchromic and batochromic shift in the absorption band. When in the presence of this surfactant, the membranes showed lower detection limits and higher selectivity.

Cervical length varies considering different populations and gestational outcomes: Results from a systematic review and meta-analysis.

BACKGROUND: The uterine cervical length is an important risk factor for preterm birth. The aim of this study was to assess cervical length distribution in women with singleton pregnancies, measured by transvaginal ultrasound between 16 and 24 weeks, and its association with population characteristics. MATERIALS AND METHODS: We searched electronic databases and other sources for studies published from April 1, 1990 to July 21, 2020. Of the 2019 retrieved publications, full-text versions of 137 articles were considered. We included 77 original articles that reported cervical length measurements of 363,431 women. The main aim of this study was to identify the pattern of cervical length in different populations. We collected demographic and clinical data concerning the population, in addition to information regarding the ultrasound examination and cervical length measurement. Regarding study bias, 56 were at low risk of bias and 21 were at medium risk of bias. RESULTS: The meta-analysis included 57 articles with data from 158,346 women. The mean cervical length was 37.96. mm (95% CI [36.68, 39.24]). Cervical length was shorter in women from Africa and Asia, in those from low-income countries, with a lower body weight, and in those who delivered before 37 gestational weeks. We found that the cervical length from pooled studies is longer than that usually discussed in the literature. Regarding limitations, we had difficulty assessing our main variable because there was no consistent pattern in the way authors reported cervical length measurement. Another limitation was the great heterogeneity between studies. CONCLUSIONS: The use of a single cutoff value to define a short cervix diagnosis, an important risk factor for preterm birth, may not be correct and cervical length must be considered according to maternal population characteristics. Future studies should identify different specific curves and cutoff values for cervical length in different populations. This meta-analysis was registered in the PROSPERO database under CRD42017070246 at https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=70246.

Anti-inflammatory potential of Portuguese thermal waters.

In light of Medical Hydrology, thermal waters (TW) are all-natural mineral waters that emerge inside a thermal resort and have therapeutic applications. Their beneficial effect has been empirically recognized for centuries, being indicated for symptom alleviation and/or treatment of several diseases, almost all associated with inflammation. Indeed, an anti-inflammatory effect has been attributed to many different Portuguese TW but there is no scientific validation supporting this empiric knowledge. In the present study, we aimed to investigate the anti-inflammatory properties of 14 TW pertaining to thermal centers located in the Central Region of Portugal, and grouped according to their ionic profile. Mouse macrophage cells stimulated with lipopolysaccharide (LPS), a Toll-like receptor 4 agonist, were exposed to culture medium prepared in TW. Metabolism, nitric oxide (NO) production, inducible nitric oxide synthase (iNOS) expression levels and the scavenging capacity of TW, were investigated in vitro. 11 out of 14 TW reduced NO production and/or iNOS expression, and/or scavenging activity, in macrophages exposed to LPS. The sulphated/calcic TW did not show any effect on at least one of the inflammatory parameters evaluated. Two sulphurous/bicarbonate/sodic TW and the sulphurous/chlorinated/sodic TW promoted an increase in NO production and/or iNOS expression. Our results validate, for the first time, the anti-inflammatory properties of Portuguese TW, supporting their therapeutic use in the treatment of inflammation-related diseases and promoting their putative application in cosmetic products and medical devices.

The comparison of different multilayer perceptron and General Regression Neural Networks for volume fraction prediction using MCNPX code.

This research presents a methodology for volume fraction predictions in water-gas-oil multiphase systems based on gamma-ray densitometry and artificial neural networks. The simulated geometry uses a dual-energy gamma-ray source and dual-modality (transmitted and scattered beams). The Am-241 and Cs-137 sources and two NaI(Tl) detectors have been used in this methodology. Different data from the pulse height distribution were used to train the artificial neural network to evaluate the volume fraction prediction. The MCNPX code has been used to develop the theoretical model for stratified regime and to provide data for the artificial neural network. 5-layers feed-forward multilayer perceptron using backpropagation training algorithm and General Regression Neural Networks has been used with different designs. The artificial neural network design that presented the best results of volume fraction prediction has a mean relative error below 2.0%.

Dissolved Carbon Dioxide Sensing Platform for Freshwater and Saline Water Applications: Characterization and Validation in Aquaculture Environments.

A sensing configuration for the real-time monitoring, detection, and quantification of dissolved carbon dioxide (dCO2) was developed for aquaculture and other applications in freshwater and saline water. A chemical sensing membrane, based on a colorimetric indicator, is combined with multimode optical fiber and a dual wavelength light-emitting diode (LED) to measure the dCO2-induced absorbance changes in a self-referenced ratiometric scheme. The detection and processing were achieved with an embeded solution having a mini spectrometer and microcontroller. For optrode calibration, chemical standard solutions using sodium carbonate in acid media were used. Preliminary results in a laboratory environment showed sensitivity for small added amounts of CO2 (0.25 mg·L-1). Accuracy and response time were not affected by the type of solution, while precision was affected by salinity. Calibration in freshwater showed a limit of detection (LOD) and a limit of quantification (LOQ) of 1.23 and 1.87 mg·L-1, respectively. Results in saline water (2.5%) showed a LOD and LOQ of 1.05 and 1.16 mg·L-1, respectively. Generally, performance was improved when moving from fresh to saline water. Studies on the dynamics of dissolved CO2 in a recirculating shallow raceway system (SRS+RAS) prototype showed higher precision than the tested commercial sensor. The new sensor is a compact and robust device, and unlike other sensors used in aquaculture, stirring is not required for correct and fast detection. Tests performed showed that this new sensor has a fast accurate detection as well as a strong potential for assessing dCO2 dynamics in aquaculture applications.

Disposable electrochemical detection of breast cancer tumour marker CA 15-3 using poly(Toluidine Blue) as imprinted polymer receptor.

In this work, electrically-conducting poly(Toludine Blue) was employed for the first time as synthetic receptor film, prepared by Molecular Imprinting strategies and using electrochemical methods, for the specific screening of breast cancer biomarker Carbohydrate Antigen 15-3 (CA 15-3). The protein imprinted poly(Toluidine Blue) film was grown in a pre-formed Toluidine Blue (TB) tailed SAM at the AuSPE surface, which greatly enhanced the stability against degradation of the Molecular Imprinted Polymer (MIP) film at the electrode surface. The MIP receptor film recognition ability towards the protein was investigated by fitting data to Freundlich isotherm. The binding affinity (KF) obtained for the MIP system was significantly higher (~ 12-fold) to that obtained for the NIP system, demonstrating the success of the approach in creating imprinted materials that specifically respond to CA 15-3 protein. The incubation of the MIP modified electrode with increasing concentration of protein (from 0.10 U mL-1 to 1000 U mL-1) resulted in a decrease of the ferro/ferricyanide redox current. The device displayed linear response from 0.10 U mL-1 to 100 U mL-1 and LODs below 0.10 U mL-1 were obtained from calibration curves built in neutral buffer and diluted artificial serum, using DPV technique, enabling the detection of the protein biomarker at clinically relevant levels. The developed MIP biosensor was applied to the determination of CA 15-3 in spiked serum samples with satisfactory results. The developed device provides a new strategy for sensitive, rapid, simple and cost-effective screening of CA 15-3 biomarker. Importantly, the overall approach seems suitable for point-of-care (PoC) use in clinical context.

Effect of porcine somatotropin on metabolism, testicular size and sperm characteristics in young boars / Efeito da somatotrofina suína sobre o metabolismo, o tamanho testicular e a qualidade espermática de cachaços jovens

The aim of this study was to evaluate the effect of pST injections on metabolism, testicular size, and sperm characteristics in young boars. Sixty 22-day old piglets were divided into two groups: pST (n=30) and Control (n=30). The pST group was submitted to pST injections (90µg/kg body weight) every three days up to 330 days of age. Blood collections were performed weekly. Testicular weight was measures at 22, 82, 142, 202 and 365 days of age. Libido and fresh semen characteristics were evaluated between 150 and 210 days of age. Semen characteristics were also evaluated during a 72h storage period (15ºC). Testosterone, albumin, and phosphorus blood concentrations were higher in the pST group (P<0.05). The pST group had a higher IGF-I concentration in seminal plasma (P=0.05) and higher testicular weight (P<0.001) compared to the Control group. The pST group had higher ejaculate volume (P<0.001), total sperm count (P=0.047) and number of inseminating doses/ejaculate (P=0.047). During the 72h storage period, the pST group had a lower number of morphological alterations (P<0.001) compared to the Control group. In sum, pST injection in young boars increased testosterone concentration, testicular size, and sperm quality.(AU)

O objetivo deste estudo foi determinar o efeito da administração de pST sobre o metabolismo, o tamanho testicular e a qualidade espermática de cachaços jovens. Foram usados leitões com 22 dias de idade, divididos em dois grupos: pST (n=30) e controle (n=30). O grupo pST foi submetido a injeções de pST (90µg/kg de peso vivo) a cada três dias até 330 dias de idade. Peso testicular foi avaliado aos 22, 82, 142, 202 e 365 dias de idade. Libido e qualidade do sêmen fresco foram avaliados entre 150 e 210 dias de idade. Qualidade espermática foi avaliada durante refrigeração (15ºC) por um período de 72 horas. Concentrações sanguíneas de testosterona, albumina e fósforo foram maiores no grupo pST (P<0,05). O grupo pST apresentou maior concentração de IGF-I no plasma seminal (P=0,05) e maior peso testicular, quando comparado ao grupo controle (P<0,001). O grupo pST apresentou maior volume espermático (P<0,001), concentração espermática (P=0,047) e número de doses espermáticas por ejaculado (P=0,047). Durante o período de 72 horas de refrigeração, o grupo pST teve menor número de patologias espermáticas (P<0,001). Assim, conclui-se que a administração de pST aumenta a concentração sanguínea de testosterona, o tamanho testicular e a qualidade espermática de cachaços jovens.(AU)

Relationship between Hammett's parameters and in silico density functional with tandem mass ESI-CID fragmentation: Dihydropyridines as prototypes.

Over the years, with the instrumental analysis evolution, the relationships between the carried-out results with the data of theoretical analysis in silico and the Hammett's parameters have been reported. They have been very useful for chemical characterization of small organic molecules. Thus, this work aims at showing the feasibility and limitations for Hammett's and density functional theory applications in electrospray ionization-collision-induced dissociation (ESI-CID) fragmentation provision. For this, 13 dihydropyrimidinones para, meta, and orto monosubstituted were studied using ESI and CID in positive mode. As a result, it was observed that the main fragmentation includes the isocyanate and ethanol loses at low energy. Nevertheless, at higher energies, radical ions formed by McLafferty rearrangement were observed. The Hammett plots were correlated fragmentation profiles, showing good linearity for the [M + H]+ , which does not occur to radical ions and carbocation's. These tendencies had demonstrated that the stability of protonate and activation energy of secondary ions changes with the pKa. The density functional theory studies indicated that, both nitrogen atoms in the dihydropyrimidinone's prototypes are capable of being protonated. However, the activation energy of fragmentation products is not changed. Therefore, this work has shown information, which can be useful to understand tandem mass spectrometry in ESI-CID conditions for small organic molecules series. This is the first step for normalization of fragmentation pathway.

Electrochemical detection of cardiac biomarker myoglobin using polyphenol as imprinted polymer receptor.

An electrochemical biosensor was developed by merging the features of Molecular Imprinting technique and Screen-Printed Electrode (SPE) for the simple and fast screening of cardiac biomarker myoglobin (Myo) in point-of-care (POC). The MIP artificial receptor for Myo was prepared by electrooxidative polymerization of phenol (Ph) on a AuSPE in the presence of Myo as template molecule. The choice of the most effective protein extraction procedure from the various extraction methods tested (mildly acidic/basic solutions, pure/mixed organic solvents, solutions containing surfactants and enzymatic digestion methods), and the optimization of the thickness of the polymer film was carefully undertaken in order to improve binding characteristics of Myo to the imprinted polymer receptor and increase the sensitivity of the MIP biosensor. The film thickness was optimized by adjusting scan rate and the number of cycles during cyclic voltammetric electropolymerization of Ph. The thickness of the polyphenol nanocoating of only few nanometres (∼4.4 nm), and similar to the protein diameter, brought in significant improvements in terms of sensor sensitivity. The binding affinity of MIP receptor film was estimated by fitting the experimental data to Freundlich isotherm and a ∼8 fold increase in the binding affinity of Myo to the imprinted polymer (KF = 0.119 ± 0.002 ng-1 mL) when compared to the non-imprinted polymer (KF = 0.015 ± 0.002 ng-1 mL) which demonstrated excellent (re)binding affinity for the imprinted protein. The incubation of the Myo MIP receptor modified electrode with increasing concentration of protein (from 0.001 ng mL-1 to 100 µg mL-1) resulted in a decrease of the ferro/ferricyanide redox current. LODs of 2.1 and 14 pg mL-1 were obtained from calibration curves built in neutral buffer and diluted artificial serum, respectively, using SWV technique, enabling the detection of the protein biomarker at clinically relevant levels. The prepared MIP biosensor was applied to the determination of Myo spiked serum samples with satisfactory results.

Toxicological impact of cadmium-based quantum dots towards aquatic biota: Effect of natural sunlight exposure.

Cadmium-based quantum dots (QDs) are increasingly applied in existent and emerging technologies, especially in biological applications due to their exceptional photophysical and functionalization properties. However, they are very toxic compounds due to the high reactive and toxic cadmium core. The present study aimed to determine the toxicity of three different QDs (CdS 380, CdS 480 and CdSeS/ZnS) before and after the exposure of suspensions to sunlight, in order to assess the effect of environmentally relevant irradiation levels in their toxicity, which will act after their release to the environment. Therefore, a battery of ecotoxicological tests was performed with organisms that cover different functional and trophic levels, such as Vibrio fischeri, Raphidocelis subcapitata, Chlorella vulgaris and Daphnia magna. The results showed that core-shell type QDs showed lower toxic effects to V. fischeri in comparison to core type QDs before sunlight exposure. However, after sunlight exposure, there was a decrease of CdS 380 and CdS 480 QD toxicity to bacterium. Also, after sunlight exposure, an effective decrease of CdSeS/ZnS and CdS 480 toxicity for D. magna and R. subcapitata, and an evident increase in CdS 380 QD toxicity, at least for D. magna, were observed. The results of this study suggest that sunlight exposure has an effect in the aggregation and precipitation reactions of larger QDs, causing the degradation of functional groups and formation of larger bulks which may be less prone to photo-oxidation due to their diminished surface area. The same aggregation behaviour after sunlight exposure was observed for bare QDs. These results further emphasize that the shell of QDs seems to make them less harmful to aquatic biota, both under standard environmental conditions and after the exposure to a relevant abiotic factor like sunlight.

Visceral leishmaniasis after orthotopic liver transplantation: a rare cause of infection.

Visceral leishmaniasis (VL) was known as an opportunistic infection associated with immunosuppression, particularly related to human immunodeficiency virus infection and rarely to solid organ transplant recipients. We report a case of VL, 6 months after liver transplantation, in a patient who presented with febrile pancytopenia. The diagnosis was made by demonstration of amastigotes in smears from bone marrow. VL is a very rare infection in patients who undergo liver transplantation and, to our knowledge, this is the first case diagnosed in Portugal.

D2 dopamine receptor regulation of learning, sleep and plasticity.

Dopamine and sleep have been independently linked with hippocampus-dependent learning. Since D2 dopaminergic transmission is required for the occurrence of rapid-eye-movement (REM) sleep, it is possible that dopamine affects learning by way of changes in post-acquisition REM sleep. To investigate this hypothesis, we first assessed whether D2 dopaminergic modulation in mice affects novel object preference, a hippocampus-dependent task. Animals trained in the dark period, when sleep is reduced, did not improve significantly in performance when tested 24h after training. In contrast, animals trained in the sleep-rich light period showed significant learning after 24h. When injected with the D2 inverse agonist haloperidol immediately after the exploration of novel objects, animals trained in the light period showed reduced novelty preference upon retesting 24h later. Next we investigated whether haloperidol affected the protein levels of plasticity factors shown to be up-regulated in an experience-dependent manner during REM sleep. Haloperidol decreased post-exploration hippocampal protein levels at 3h, 6h and 12h for phosphorylated Ca(2+)/calmodulin-dependent protein kinase II, at 6h for Zif-268; and at 12h for the brain-derived neurotrophic factor. Electrophysiological and kinematic recordings showed a significant decrease in the amount of REM sleep following haloperidol injection, while slow-wave sleep remained unaltered. Importantly, REM sleep decrease across animals was strongly correlated with deficits in novelty preference (Rho=0.56, p=0.012). Altogether, the results suggest that the dopaminergic regulation of REM sleep affects learning by modulating post-training levels of calcium-dependent plasticity factors.

Organ transplants and education: experience of the Universidade Federal de Ciências da Saúde de Porto Alegre with subjects.

INTRODUCTION: Today there is an insufficient number of donated organs in Brazil. This is particularly due to the general population's and health care professionals' lack of information. Therefore, with this project we intend to consolidate knowledge on organ donation to teach health care students of different areas so they are able to propagate such knowledge. MATERIALS AND METHODS: In 2006, at Universidade Federal de Ciências da Saúde de Porto Alegre, an "Organ donation and transplants" subject was created, with the aim to educate health care students. In the next years, it was split in two subjects, named "Introduction to transplants" and "Donation and transplants." By enrolling, students get theoretical classes and practical experience in out- and inpatient facilities and in surgical environments at the Santa Casa Hospital Complex. Furthermore, they can participate in campaigns at parks, stadiums, and health care fairs that take place at several schools in Porto Alegre. To finish the subjects, students present a conclusion report. RESULTS: Seven years after implementation of the subject, and with more than 400 students enrolled, several accomplishments can be highlighted. For example, the creation of the Organ Transplantation League, the implementation of a day to spread conception of the donation-transplant process (with the elaboration of a Web page on the subject), and the release of a book on the subject written by students and professors. DISCUSSION AND CONCLUSION: Health care professionals' education is a central point in donation and transplant process. This is because they become, inevitably, educators, and this brings a long-term consequence, consisting of enhanced logistics skills on brain-death diagnosis and further transfer of information to the population (hopefully reducing denial by families at the time of the donation). We conclude that this is a project to be followed by other medical schools so that, effectively, the number of donors increases and, consequently, the transplantation of organs and tissues as well.

The role of endoplasmic reticulum in amyloid precursor protein processing and trafficking: implications for Alzheimer's disease.

The endoplasmic reticulum (ER) is the principal organelle responsible for the proper folding/processing of nascent proteins and perturbed ER function leads to a state known as ER stress. Mammalian cells try to overcome ER stress through a set of protein signaling pathways and transcription factors termed the unfolded protein response (UPR). However, under unresolvable ER stress conditions, the UPR is hyperactivated inducing cell dysfunction and death. The accumulation of misfolded proteins in the brain of Alzheimer's disease (AD) patients suggests that alterations in ER homeostasis might be implicated in the neurodegenerative events that characterize this disorder. This review discusses the involvement of ER stress in the pathogenesis of AD, focusing the processing and trafficking of the AD-related amyloid precursor protein (APP) during disease development. The potential role of ER as a therapeutic target in AD will also be debated.

Protective effect of leptin and ghrelin against toxicity induced by amyloid-ß oligomers in a hypothalamic cell line.

In addition to cognitive decline, Alzheimer's disease (AD) patients also exhibit an unexplained weight loss that correlates with disease progression. In young and middle-aged AD patients, large amounts of amyloid-ß (Aß) deposits were observed in the hypothalamus, a brain region involved in the control of feeding and body weight through the action of peripheral metabolic peptides, which have recently been shown to have neuroprotective effects. Moreover, levels of peripheral metabolic peptides, such as leptin and ghrelin, are changed in AD patients. The present study aimed to investigate the role of Aß peptide in the survival of hypothalamic cells and to explore the receptor-mediated protective effect of leptin and ghrelin against Aß-induced toxicity in these cells. Using the mHypoE-N42 cell line, we demonstrated for the first time that oligomeric Aß is toxic to hypothalamic cells, leading to cell death. It was also demonstrated that leptin and ghrelin protect these cells against AßO-induced cell death through the activation of the leptin and ghrelin receptors, respectively. Furthermore, ghrelin and leptin prevented superoxide production, calcium rise and mitochondrial dysfunction triggered by AßO. Taken together, these results suggest that peripheral metabolic peptides, in particular leptin and ghrelin, might be considered as preventive strategies for ameliorating hypothalamic alterations in AD.

Insect Seed Predators in Erythrina falcata (Fabaceae): Identification of Predatory Species and Ecological Consequences of Asynchronous Flowering.

Seed predation by insects exerts negative effects on plant reproduction by limiting the supply of seeds and preventing germination. Seed predators of the family Fabaceae are usually generalists, which increases the rate of predation. One strategy to minimize seed predation, developed by plants from temperate regions, is "escape in time," i.e., flowering before or after the peak of predation. For tropical species, few studies have investigated the strategies used by plants to minimize seed predation. Here, using Erythrina falcata, a tropical species of Fabaceae, we test three main hypotheses: (i) escape in time is a mechanism used by E. falcata to minimize seed predation, (ii) the predators of E. falcata seeds are generalists, and (iii) the biometric variables of the pods can influence seed predation. In order to test these hypotheses, we determined the flowering time of E. falcata, rate of seed predation, the predators insects, and biometric variables of the pods. The analyzed trees were grouped into three classes: "early," "peak," and "late" flowering. The average seed predation rates on trees in the early and late classes were 65% and 50%, respectively, and in the peak class, 80%; thus, our first hypothesis can be accepted. Three species of Lepidoptera and two of Coleoptera were found preying on E. falcata seeds. These species were observed to be generalist predators; thus, our second hypothesis can be accepted. The biometric variables of the pods cannot influence seed predation rate. The ecological consequences of asynchronous flowering on plants and insects are discussed.

Antifungal susceptibility, exoenzyme production and cytotoxicity of novel oximes against Candida.

Novel oximes were synthesized, their in vitro antifungal activity against Candida was evaluated and their cytotoxicity was determined. The procedure used for the synthesis of the oximes is aligned with the current green chemistry trend; water is employed as the solvent in this reaction. The minimum inhibitory and minimum fungicidal concentrations of the oximes were evaluated using the CLSI M27-A3 method. The influence of these compounds on the inhibition of the production of hydrolytic enzymes, phospholipase and proteinase by Candida was also investigated. The compounds showed a good ability to inhibit phospholipase, with a 50 % reduction in most cases. However, the tested compounds did not affect proteinase. The current results showed a substantial reduction in the phospholipase production, which suggests that compounds of this class may interfere with host infection and disease progression. The oximes examined showed lower fungicidal activities than fluconazole but interfered significantly with the expression of phospholipase. Some of the oximes included in this study could be a suitable matrix for the development of novel antifungal compounds.

Self-etching dental adhesive containing a natural essential oil: anti-biofouling performance and mechanical properties.

This study assessed the anti-biofouling performance of an experimental adhesive system containing a naturally occurring essential vegetable oil and examined the following physical and mechanical properties: water sorption (WS) and solubility (SL), microtensile bond strength to dentin (µTBS), and degree of conversion. The following six groups were tested: a self-etching experimental adhesive containing refined essential oil from the seeds of the Butia capitata tree (EAO); an oil-free version of the experimental adhesive (EANO); one group without adhesive as the control (C); and the three following commercial self-etching adhesives: Clearfil Protect Bond (CPB), Clearfil SE Bond, and Adper SE Plus. The antibacterial effect was estimated by microbiological culture on selective/non-selective media, and the results expressed as colony-forming units per unit weight of dry biofilm (CFU mg(-1)). The data were submitted to ANOVA and Tukey's post hoc test (α = 0.05). After 24 h, pH changes were similar in the storage medium of all tested adhesive systems. EAO showed similar levels of antimicrobial activity in a model biofilm microcosm as the commercial self-etching adhesive CPB. Both were effective against total microorganisms, aciduric bacteria, lactobacilli, and Streptococcus mutans. WS and SL were not affected by the presence of the essential oil; the values of EAO were similar to or less than those of commercial equivalents. The incorporation of an essential oil into an experimental adhesive did not influence its monomer conversion result. Immediate µTBS values of EAO and EANO were similar and were greater than those of commercial equivalents. After storage for 6 months, the µTBS of the EAO decreased significantly and became similar to the values of commercial equivalents, while the strength of the EANO was not affected.

Leptin and ghrelin prevent hippocampal dysfunction induced by Aß oligomers.

It was recently established that the stomach-derived ghrelin and the adipokine leptin promote learning and memory through actions within the hippocampus. Changes in the peripheral or brain levels of these peptides were described in Alzheimer's disease (AD) patients and were shown to correlate with the severity of cognitive decline. Furthermore, in vivo and in vitro studies demonstrated that leptin or ghrelin can ameliorate amyloid and tau pathologies as well as cognitive deficits. However, the exact role of these peptides in AD is far from being elucidated. To fill this gap, our working hypothesis was that leptin and ghrelin can exert a neuroprotective role in AD suppressing hippocampal dysfunction triggered by synapto- and neurotoxic amyloid-ß oligomers (AßO). Using primary cultured hippocampal neurons, we demonstrated that both peptides reduce AßO-induced production of superoxide and mitochondrial membrane depolarization, improving cell survival, and inhibit cell death through a receptor-dependent mechanism. Furthermore, it was shown that in AßO-treated neurons both leptin and ghrelin prevent glycogen synthase kinase 3ß activation. Therefore, the evidence gathered in this study revealed that leptin and ghrelin can act as neuroprotective agents able to rescue hippocampal neurons from AßO toxicity, thus highlighting their potential therapeutic role in AD.

Epigenetic regulation of BACE1 in Alzheimer's disease patients and in transgenic mice.

In Alzheimer's disease (AD) the complex interplay between environment and genetics has hampered the identification of effective therapeutics. However, epigenetic mechanisms could underlie this complexity. Here, we explored the potential role of epigenetic alterations in AD by investigating gene expression levels and chromatin remodeling in selected AD-related genes. Analysis was performed in the brain of the triple transgenic animal model of AD (3xTg-AD) and in peripheral blood mononuclear cells (PBMCs) from patients diagnosed with AD or Mild Cognitive Impairment (MCI). BACE1 mRNA levels were increased in aged 3xTg-AD mice as well as in AD PBMCs along with an increase in promoter accessibility and histone H3 acetylation, while the BACE1 promoter region was less accessible in PBMCs from MCI individuals. Ncstn was downregulated in aged 3xTg-AD brains with a condensation of chromatin and Sirt1 mRNA levels were decreased in these animals despite alterations in histone H3 acetylation. Neither gene was altered in AD PBMCs. The ADORA2A gene was not altered in patients or in the 3xTg-AD mice. Overall, our results suggest that chromatin remodeling plays a role in mRNA alterations in AD, prompting for broader and more detailed studies of chromatin and other epigenetic alterations and their potential use as biomarkers in AD.