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Working memory performance declined for all animals during SDHF, in which agonistic conflicts are increased. However, living within an established hierarchical social network for several weeks deteriorated the working memory performance of dominant and middle-ranked animals, while the performance of subordinates improved and got significantly better than higher-ranked animals. In conclusion, while working memory and social status were correlated positively before dominance hierarchy formation, there was a trade-off between them after the formation of it. In contrast to the common view, these results highlight the adverse effect of higher social status on cognitive behavior.Alcohol use disorder needs more effective treatments because relapse rates remain high. Psychedelics, such as ayahuasca, have been used to treat substance use disorders. Our study aimed to evaluate the effects of ayahuasca on ethanol-induced behavioral sensitization (EIBS). Swiss mice received 2.2 g/kg ethanol or saline IP injections every other day across nine days (D1, D3, D5, D7, and D9), and locomotor activity was evaluated 10 min after each injection. Then, animals were treated daily with ayahuasca (corresponding to 1.76 mg/kg of N,N-dimethyltryptamine, DMT) or water by oral gavage for eight consecutive days. On the seventh day, mice were evaluated in the elevated plus maze. Then, mice were challenged with a single dose of ethanol to measure their locomotor activity. Dopamine receptors, serotonin receptors, dynorphin, and prodynorphin levels were quantified in the striatum and hippocampus by blot analysis. Repeated ethanol administration resulted in EIBS. However, those animals treated with ayahuasca had an attenuated EIBS. Moreover, ayahuasca reduced the anxiogenic response to ethanol withdrawal and prevented the ethanol-induced changes on 5-HT1a receptor and prodynorphin levels in the hippocampus and reduced ethanol effects in the dynorphin/prodynorphin ratio levels in the striatum. These results suggest a potential application of ayahuasca to modulate the neuroplastic changes induced by ethanol.The prepulse inhibition (PPI) of the startle response can identify the rodents that are more sensitive to the effects of cocaine. Mice with a lower PPI presented a higher vulnerability to the effects of cocaine and a higher susceptibility to developing a substance use disorder (SUD). Maternal separation with early weaning (MSEW) is a relevant animal model to induce motivational alterations throughout life. Nevertheless, only a few studies on females exist, even though they are more vulnerable to stress- and cocaine-related problems. Hence, the aim of the present study was to evaluate the ability of PPI to identify females with a greater vulnerability to the long-term consequences of early stress on the motivational effects of cocaine. Female mice underwent MSEW and were classified according to their high or low PPI. They were then assessed in the cocaine-induced locomotor sensitization test, the conditioned place preference paradigm or the operant self-administration paradigm. Additionally, they were also evaluated in the passive avoidance task, the tail-suspension and the splash tests. The results revealed that the females with lower PPI presented higher consequences of MSEW on the effects of cocaine and showed an increase in anhedonia-like behaviours. Our findings support that a PPI deficit could represent a biomarker of vulnerability to the effects of cocaine induced by MSEW.Deep brain stimulation paradigms might be used to treat memory disorders in patients with stroke or traumatic brain injury. However, proof of concept studies in animal models are needed before clinical translation. We propose here a comprehensive review of rodent models for Traumatic Brain Injury and Stroke. We systematically review the histological, behavioral and electrophysiological features of each model and identify those that are the most relevant for translational research.Fundamental work on the mechanisms leading to focal epileptic discharges in mesial temporal lobe epilepsy (MTLE) often rests on the use of rodent models in which an initial status epilepticus (SE) is induced by kainic acid or pilocarpine. In 2008 we reviewed how, following systemic injection of pilocarpine, the main subsequent events are the initial SE, the latent period, and the chronic epileptic state. Up to a decade ago, rats were most often employed and they were frequently analysed only behaviorally. However, the use of transgenic mice has revealed novel information regarding this animal model. Here, we review recent findings showing the existence of specific neuronal events during both latent and chronic states, and how optogenetic activation of specific cell populations modulate spontaneous seizures. We also address neuronal damage induced by pilocarpine treatment, the role of neuroinflammation, and the influence of circadian and estrous cycles. Updating these findings leads us to propose that the rodent pilocarpine model continues to represent a valuable tool for identifying the basic pathophysiology of MTLE.

There is conflicting observational data on the survival benefit cardiac implantable electronic devices (CIED) in patients with LVADs.

Patients in whom an LVAD was implanted between January 2008 and April 2017 in the multinational Trans-Atlantic Registry on VAD and Transplant (TRAViATA) registry were separated into four groups based on the presence of CIED prior to LVAD implantation none (n=146), implantable cardiac defibrillator (ICD) (n=239), cardiac resynchronization without defibrillator (CRT-P) (n=28), and CRT with defibrillator (CRT-D) (n=111).

A total of 524 patients (age 52years ±12, 84.4% male) were followed for 354 (interquartile range 166-701) days. After multivariable adjustment, there were no differences in survival across the groups. In comparison to no device, only CRT-D was associated with late right ventricular failure (RVF) (hazard ratio 2.85, 95% confidence interval [CI] 1.42-5.72, p=0.003). There was no difference in risk of early RVF across the groups or risk of ICD shocks between those with ICD and CRT-D.

In a multinational registry of patients with LVADs, there were no differences in survival with respect to CIED subtype. However, patients with a pre-existing CRT-D had a higher likelihood of late RVF suggesting significant long-term morbidity in those with devices capable of LV‑lead pacing post LVAD implantation.

In a multinational registry of patients with LVADs, there were no differences in survival with respect to CIED subtype. However, patients with a pre-existing CRT-D had a higher likelihood of late RVF suggesting significant long-term morbidity in those with devices capable of LV‑lead pacing post LVAD implantation.

Assisted reproductive technologies (ART) induce premature vascular aging in human offspring. The related alterations are well-established risk factors for stroke and predictors of adverse stroke outcome. However, given the young age of the human ART population there is no information on the incidence and outcome of cerebrovascular complications in humans . In mice, ART alters the cardiovascular phenotype similarly to humans, thereby offering the possibility to study this problem.

We investigated the morphological and clinical outcome after ischemia/reperfusion brain injury induced by transient (45 min) middle cerebral artery occlusion in ART and control mice.

We found that stroke volumes were almost 3-fold larger in ART than in control mice (P < 0.001). In line with these morphological differences, neurological performance assessed by the Bederson and RotaRod tests 24 and 48 h after artery occlusion was significantly worse in ART compared with control mice. Plasma levels of TNF-alpha, were also signind encourage early preventive and diagnostic efforts.

This study highlights that ART not only is a risk factor for stroke-occurrence, but also a mediator of adverse stroke-outcome. The findings should raise awareness in the ever-growing human ART population in whom these techniques cause similar alterations of the cardiovascular phenotype and encourage early preventive and diagnostic efforts.

Cancer stem cells (CSC) are the most common causes of lung cancer relapse and mouse resistance to chemotherapy. CD166 was identified as CSC marker for lung cancer. Our study aimed to detect the effect of dendritic cell vaccine loaded with tumor cell lysate (TCL-DCV) on percentage of CD166

CSC in lung of mice exposed to Benzo(a)Pyrene (BP).

Female albino mice were divided into 5 groups (22 mice per group) normal control (NC), lung cancer control (LCC) (50mg/kg BP orally, twice weekly for four weeks), dendritic cell (DC), TCL-DCV and cisplatin. Cisplatin (6mg/kg, intraperitoneal) was given in two doses (18th and 20th week). 1×10

cells of each of DC and TCL-DCV was given subcutaneously as cisplatin. At the end of experiment (22weeks), lung tissue was used for evaluation of cytotoxic T lymphocyte antigen-4 (Ctla-4), transforming growth factor-β (Tgf-β), forkhead box protein P3 (Foxp3), programmed death ligand 1 (Pd-l1) and interleukin 12 (Il-12) gene expression using quantitative RT-PCR. The percentage of CD83

, CD8

and CD166

cells in lung tissue were measured using flow cytometry.

The results revealed that TCL-DCV reversed the tumorigenic effect of BP in the lung as evidenced by histopathological examination. Compared to cisplatin, dendritic cell vaccination (TCL-DCV) significantly decreased percentage of CD166

CSC. Y27632 This anticancer stemness effect was attributed to the immune-stimulatory effect as indicated by increased percentage of CD83

and CD8

cells, upregulation of Il-12, and downregulation of Tgf-β, Ctla-4, Pd-l1 and Foxp3 gene expression compared to LCC group.

TCL-DCV ameliorated cancer stemness through modulating tumor immune archetypes which make it a potent therapeutic alternative to chemotherapy resistant cases.

TCL-DCV ameliorated cancer stemness through modulating tumor immune archetypes which make it a potent therapeutic alternative to chemotherapy resistant cases.Metals and metalloids including lead (Pb), arsenic (As) and manganese (Mn) can occur as mixtures in occupational contexts, such as mines. These chemicals are all known to be neurotoxic and provoke changes in heme metabolism also known to induce neurotoxicity. The objective of this work was to propose a multi-biomarker (BM) methodology to screen subjects exposed to the mixture of Pb, As and Mn and assess the severity of their exposure/effects, in an individual basis. The urinary levels of the metals, dela-aminolevulinic acid (ALA) and porphyrins were determined in Portuguese miners and in a control group. The combination of Pb and As urinary levels had the highest capability to identify subjects occupationally exposed to this mixture in mines, as evaluated through Receiver Operating Characteristic (ROC) (A = 98.2%; p less then 0.05), allowing that 94.2% of 86 studied subjects were properly identified and the generation of an equation indicating the odd of a subject be considered as exposed to the metal mixture. The combination of urinary ALA and porphyrins revealed to be best one to be applied in the assessment of subjects with high, intermediate, and low magnitudes of exposure/effects, with 95.7% of 46 miners classified correctly according to their severity sub-group and allowing to generate equations, which can be applied in new subjects. The proposed methodology showed a satisfactory performance, evaluating in an integrated manner the magnitude of exposure/effects of the exposed workers, may contributing to improve the control of their health.

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