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Identifying adults with congenital heart disease (CHD) at high risk for sudden death who stand to benefit from primary prevention implantable cardioverter-defibrillators (ICDs) remains a major challenge. Inconsistencies among evidence-based recommendations by various professional societies can be a source of confusion to practicing clinicians. This article summarizes and compares recommendations from the Canadian Cardiovascular Society management guidelines on adults with CHD (2009), expert consensus from the Pediatric and Congenital Electrophysiology Society and Heart Rhythm Society (2014), European Society of Cardiology (ESC) guidelines on sudden death (2015), position statement from the European Heart Rhythm Association, Association for European Paediatric and Congenital Cardiology, and ESC working group on grown-up CHD (2018), and ESC guidelines on adult CHD (2020). Tanespimycin in vitro Most recommendations are fundamentally similar, particularly with regards to 1) recommending or considering primary prevention ICDs in adults with CHD and a systemic left ventricular ejection fraction ≤35%, biventricular physiology, and functional class II or III symptoms despite optimal medical therapy; 2) considering ICDs in those with unexplained syncope of suspected arrhythmic etiology and either advanced ventricular dysfunction or inducible sustained ventricular arrhythmias; and 3) considering ICDs in selected patients with tetralogy of Fallot and multiple risk factors for sudden death, such as left ventricular dysfunction, non-sustained ventricular tachycardia, QRS duration ≥180 ms, right ventricular scarring, or inducible sustained ventricular tachycardia. Areas of continued clinical uncertainty, which offer important opportunities for future research, include improving patient selection for primary prevention ICDs in the context of a systemic right ventricle, univentricular heart, or Eisenmenger syndrome.Developing more soluble and stable nanoformulation for the potent anticancer complex of copper diethyldithiocarbamate (CD) is extremely desired. Herein, for the first time, CD nanoparticles (NPs) were formulated by chelating diethyldithiocarbamate to bacterially and green chemically prepared copper oxide NPs (Bio CO NPs and Chemo CO NPs, respectively). Chemo CO NPs were produced in simpler and less time-consuming manner with higher NPs homogeneity. These CO NPs were identified, by X-ray diffractometer, as CuO and Cu2O, respectively. The nanoformulated CD complexes (Bio CD NPs and Chemo CD NPs) which have nanosizes (215.7 nm and 148.1 nm, respectively) with negative zeta potentials (∼-20 mv), exhibited not only high serum stability and solubility but also a potent anticancer effect. More importantly, Chemo CD NPs outperformed Bio CD NPs in the terms of synergistic anticancer index, apoptosis induction (>81% and less then 54%, respectively) and anti-migration efficacy (≥80% and less then 71%, respectively). This could be attributed to smaller nanosize and Cu2O of Chemo CD NPs causing higher cellular uptake with stronger inhibition of aldehyde dehydrogenase 1A1 and more free radical generation in Chemo CD NPs-treated cancer cells than Bio CD NPs. This distinct anticancer efficacy of novel Chemo CD NPs deserves further investigation using animal models.Orexin receptors expressed in basolateral amygdala (BLA) have been proposed for memory processing and hippocampal plasticity. There are several investigations about the effect of the adrenergic system in BLA on memory enhancement. However, there is no information about the molecular basis of this effect. Adrenergic and orexinergic fibers are found in BLA. In this study, the effects of both adrenergic and orexinergic systems were investigated on the amygdala function. To this end, the selective beta 2 adrenergic agonist (clenbuterol) and orexin receptors' antagonists (OX1R and OX2R, SB-334867-A and TCS-OX2-29, respectively) were administered into the BLA, then the high frequency stimulation (200-Hz) was applied to the perforant pathway and the synaptic plasticity of the dentate granular cells was studied in anaesthetized rats. Clenbuterol injection into the BLA enhanced the population spike (PS) component of LTP in the dentate gyrus (DG), as compared to that observed after dimethyl sulfoxide treatment. In addition, after orexin 1 or 2 receptor antagonists (SB-334867-A and TCS-OX2-29, respectively) injecting into the BLA, the enhancing effect of clenbuterol on PS was reduced. Moreover, the population excitatory post-synaptic potential also decreased in the SB-clenbuterol and TCS- clenbuterol experimental groups. However, the PS amplitude was also decreased in the group treated only by SB or TCS relative to the clenbuterol treated group. The PS amplitude or EPSP slope in the groups treated by both application of orexin receptors' antagonists and clenbuterol was considerably lower relative to the groups treated only by orexin receptors' antagonists. It is concluded that the BLA orexinergic system modulates hippocampal plasticity in relation with the adrenergic system.Toxoplasma gondii (T. gondii) is an intracellular protozoan that infects the fetus through the placenta and leads to severe complications in the fetus. One of the complications of congenital toxoplasmosis is spontaneous abortion. The prevalence of toxoplasmosis infection was investigated among spontaneously aborted fetuses (SAFs), and the genotypes of parasite isolates were determined in the present study. Placentas from 330 samples of SAFs were collected in Jahrom (Fars province) from February to September 2018. DNA was extracted from each placental tissue. The T. gondii infection was detected using nested polymerase chain reaction (Nested-PCR) assay based on a 529 bp repeat element (RE) gene. Afterward, Toxoplasma was genotyped using PCR-restriction fragment length polymorphism (PCR-RFLP) based on the GRA6 gene. The frequency of T. gondii infection was found to be 14.5% (48 out of 330 samples). Genotyping of nine T. gondii isolates revealed that all belonged to genotype II. Statistically, the prevalence of T. gondii infection was significantly correlated with the education levels of the mothers and the age of the fetus (P less then 0.05). The lowest prevalence of Toxoplasma infection belonged to mothers with university education and the highest frequency of infection was observed among the fetuses in the age group of 8-9 weeks. The findings of the present study suggest a significant role for toxoplasmosis in SAFs in Jahrom city.Vibrio alginolyticus is an important zoonotic marine pathogenic bacterium. Previous studies on the mechanism of innate immune against V. alginolyticus infection have been limited to aquatic animals, however, how V. alginolyticus activates mammalian immune cells has not been fully clarified. Here, ELISA combined RT-qPCR assays were used to detect the secretion and transcription level of pro-inflammatory cytokines and TLRs during V. alginolyticus infection of mice peritoneal macrophages (PMϕs). Western blotting was used to explore the phosphorylation levels of p38, JNK, ERK, AKT and NF-κB protein. Immunofluorescence assay was used to determine the location of NF-κB protein. Inhibition assay was used to study the role of up-regulated TLR in activated signaling pathways and the role of these pathways in the release of pro-inflammatory cytokines. Our data showed that V. alginolyticus can up-regulate the expression levels of IL-1β, IL-6, IL-12 and TNF-α in PMϕs. In addition, V. alginolyticus stimulation activated the phosphorylation of p38, JNK and ERK were TLR2 heterodimers-dependent, whereas inhibitors of SB203580 (p38), SCH772984 (ERK) and SP600125 (JNK) significantly reduced IL-1β, IL-6, IL-12 and TNF-α production. We further revealed that V. alginolyticus activated the signaling pathways of AKT via TLR2 heterodimers. The inhibitor of MK-2206 2HCl (AKT) negatively regulated the IL-1β, IL-6 and TNF-α release levels. Moreover, V. alginolyticus infection of PMϕs resulted in TLR2 heterodimers-mediated activation of NF-κB and induced translocation of phosphorylated NF-κB protein from the cytoplasm into the nucleus via IκBα degradation. V. alginolyticus induced IL-1β, IL-6, IL-12 and TNF-α release were blocked by the specific NF-κB inhibitor, BAY 11-7082. Taken together, our results suggested that activation of the TLR2 heterodimers-mediated downstream signaling pathways NF-κB, MAPK and AKT is responsible for inflammatory response during Vibrio alginolyticus infection in vitro.Ungulates visually and olfactorily discriminating between vegetation patches in grasslands often encounter restriction of target visibility due to light intensity changes; however, little is known about their performance in such a context. We developed and tested an apparatus for evaluating the visual and olfactory discrimination ability of cattle under controlled target visibility, focusing on the discrimination at a short distance. The apparatus was designed to contain a discrimination target under a sliding cover of variable light transmission levels and behind a vent of a fixed size and aperture so as to control the visibility of the target (14-100% restrictions) while ensuring a constant level of odor. Twelve Japanese Black cows were allowed to choose between two apparatuses presenting a pair of targets green forage versus empty, green forage versus dead forage, or green forage versus green-dead mixture. Cows rapidly learned to slide open the cover to reach the selected target, consistently chose the green forage against the alternative except against the green-dead mixture under 100% visual restriction, and remembered the reaching procedure for at least 16 days. The results indicate the usefulness of the apparatus for assessing close visual and olfactory discrimination ability of cattle in detail.The context specificity of habituation has been demonstrated in earthworms. After the habituation of the retraction response to a light, a recovery of the response was observed when subjects are re-habituated in a different context. Some theories assume that an association between the context and the unconditioned stimulus could underlie this result. A series of experiments were conducted in order to test this issue. We assessed the potential disruptive effects of post-exposure (extinction effect) and pre-exposure of the context (latent inhibition effect) on the establishment of a context-US association. A recovery of response during subsequent rehabituation test was expected. The results of Experiment 1 showed that the extinction was effective, the post-exposure of the context after habituation produced a recovery of the retraction response. This result was replicated in Experiment 2 where the post-exposure condition was compared with a pre-exposure one. However, the pre-exposure to the context did not result in a recovery of the response in the rehabituation test, but also produced a general decrement on the response during the habituation training, that it has been interpreted as decrement in context's salience. In summary, these results suggest the involvement of associative and nonassociative processes in habituation learning.Motivated behavior has long been studied by psychologists, ethologists, and neuroscientists. To date, many scientists agree with the view that cue and reward attraction is the product of a dopamine-dependent unconscious process called incentive salience or "wanting". This process allows the influence of multiple factors such as hunger and odors on motivational attraction. In some cases, however, the resulting motivated behavior differs from what the incentive salience hypothesis would predict. I argue that seeking behavior under reward uncertainty illustrates this situation Organisms do not just "want" (appetite-based attraction) cues that are inconsistent or associated with reward occasionally, they "hope" that those cues will consistently predict reward procurement in the ongoing trial. Said otherwise, they become motivated to invest time and energy to find consistent cue-reward associations despite no guarantee of success (effort-based attraction). A multi-test comparison of performance between individuals trained under uncertainty and certainty reveals behavioral paradoxes suggesting that the concept of incentive salience cannot fully account for responding to inconsistent cues.
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