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991.
Several studies in rodents have suggested the inactivation of the subthalamic nucleus (STN) as an alternative strategy to Parkinson's disease (PD) treatment. The STN is part of the basal ganglia and plays an important role in the motor function; however, recent data suggest that this structure has a critical role in the cognitive function of the limbic system. The STN receives direct projection from the prefrontal cortex (PFC), structure interconnected with the hippocampus and both structures send excitatory projections to the nucleus accumbens (NAcc). Here, we determined whether and which changes occurred 4 weeks after a STN lesion in the dendritic morphology of pyramidal neurons of the layers 3 and 5 of the PFC and basolateral amygdala, neurons of the ventral hippocampus, and the medium spiny neurons of the NAcc and caudate‐putamen. Dendritic morphology was measured using the Golgi‐Cox procedure followed by Sholl analysis. We also evaluated the effects of STN lesion on locomotor behavior assessed by an open field test, social interaction, acoustic startle response, prepulse inhibition, and locomotor activity induced by a novel environment and amphetamine. We found that STN damage induced a deficit in locomotion measured by open field test with neuronal hypertrophy in PFC (layer 5) and reduced spinogenesis in CA1 ventral hippocampus and PFC (layer 3). Taken together, these data suggest that the behavioral and morphological effects of STN lesion are, at least partially, mediated by limbic subregions with possible consequences for cognitive‐related behaviors observed in PD treatment. Synapse 68:114–126, 2014. © 2013 Wiley Periodicals, Inc.  相似文献   
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To understand the vulnerability of individual species to anthropogenic contamination, it is important to evaluate the different abilities of phytoplankton to respond to environmental changes induced by pollution. The ability of a species to adapt, rather than its initial tolerance, is the basis for survival under rapidly increasing levels of anthropogenic contamination. High doses of osmium (Os) cause massive destruction of diverse phytoplankton groups. In this study, we found that the coastal chlorophyte Tetraselmis suecica and the continental chlorophyte Dictyosphaerium chlorelloides were able to adapt to a lethal dose of Os. In these species, Os-resistant cells arose as a result of rare spontaneous mutations (at rates of approximately 10?6 mutants per cell division) that occurred before exposure to Os. The mutants remained in the microalgal populations by means of mutation–selection balance. The huge size of phytoplankton populations ensures that there are always enough Os-resistant mutants to guarantee the survival of the population under Os pollution. In contrast, we observed that neither a haptophyte species from open ocean regions nor a cyanobacterium from continental freshwater were able to adapt to the lethal Os dose. Adaptation of phytoplankton to Os contamination is relevant because industrial activities are leading to a rapid increase in Os pollution worldwide.  相似文献   
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The angiotensin-converting enzyme 2 (ACE2) is a type I integral membrane that was discovered two decades ago. The ACE2 exists as a transmembrane protein and as a soluble catalytic ectodomain of ACE2, also known as the soluble ACE2 that can be found in plasma and other body fluids. ACE2 regulates the local actions of the renin-angiotensin system in cardiovascular tissues, and the ACE2/Angiotensin 1–7 axis exerts protective actions in cardiovascular disease. Increasing soluble ACE2 has been associated with heart failure, cardiovascular disease, and cardiac remodelling. This is a review of the molecular structure and biochemical functions of the ACE2, as well we provided an updated on the evidence, clinical applications, and emerging potential therapies with the ACE2 in heart failure, cardiovascular disease, lung injury, and COVID-19 infection.

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996.
Purpose

Patients with chronic kidney disease are predisposed to heart rhythm disorders including atrial fibrillation (AF). Several studies have suggested that radiofrequency catheter ablation of AF improves renal function. However, little data exists for pulmonary vein isolation with cryoballoon ablation (CBA). The purpose of this study is to assess change in renal function following CBA for AF.

Method

This is a single-center retrospective study that included patients who underwent CBA for AF between 2011 and 2016. Patients were grouped by baseline-estimated glomerular filtration rate (eGFR): ≥?90 (Stage G1), 60–89.9 (Stage G2), and 30–59.9 mL/min/1.73 m2 (Stage G3). Change in eGFR was assessed >?3 months post-ablation.

Results

A total of 306 patients with both pre- and post-ablation serum creatinine measurements available were included. Baseline eGFRs for Stages G1, G2, and G3 patients were 103.5?±?12.9 (n?=?82), 74.7?±?8.2 (n?=?184), and 52.6?±?6.6 mL/min/1.73 m2 (n?=?40), respectively. Renal function was assessed 310.8?±?104.2 days post-ablation. Average intra-procedural contrast use was 58.4?±?23.8 mL. There was no significant change in eGFR following CBA in Stage G1 patients (p?=?0.10). For those with Stages G2 and G3 renal function, eGFR improved by 6.1% (4.2 mL/min/1.73 m2, p?<?0.01) and 13.8% (7.2 mL/min/1.73 m2, p?<?0.01), respectively. This improvement was seen regardless of the presence or absence of recurrent atrial arrhythmias.

Conclusions

CBA for AF may be associated with an improvement in renal function, particularly among those with a reduced baseline eGFR despite recurrence of atrial arrhythmias and intra-procedural contrast use.

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Although nonmyeloablative conditioning regimen transplantations (NMTs) induce engraftment of allogeneic stem cells with a low spectrum of toxicity, graft-versus-host disease (GVHD) remains a significant cause of morbidity and mortality. In vivo T-cell depletion, using alemtuzumab, has been shown to reduce the incidence of GVHD. However, this type of maneuver, although reducing GVHD, may have an adverse impact on disease response, because NMTs exhibit their antitumor activity by relying on a graft-versus-malignancy effect. To explore the efficacy of alemtuzumab compared with methotrexate (MTX) for GVHD prophylaxis, we have compared the results in 129 recipients of a sibling NMT enrolled in 2 prospective studies for chronic lymphoproliferative disorders. Both NMTs were based on the same combination of fludarabine and melphalan, but the United Kingdom regimen (group A) used cyclosporin A plus alemtuzumab, whereas the Spanish regimen (group B) used cyclosporin A plus MTX for GVHD prophylaxis. Patients receiving alemtuzumab had a higher incidence of cytomegalovirus (CMV) reactivation (85% versus 24%, P <.001) and a significantly lower incidence of acute GVHD (21.7% versus 45.1%, P =.006) and chronic GVHD (5% versus 66.7%, P <.001). Twenty-one percent of patients in group A and 67.5% in group B had complete or partial responses 3 months after transplantation (P <.001). Eighteen patients in group A received donor lymphocyte infusions (DLIs) to achieve disease control. At last follow-up there was no difference in disease status between the groups with 71% versus 67.5% (P =.43) of patients showing complete or partial responses in groups A and B, respectively. No significant differences were observed in event-free or overall survival between the 2 groups. In conclusion, alemtuzumab significantly reduced GVHD but its use was associated with a higher incidence of CMV reactivation. Patients receiving alemtuzumab often required DLIs to achieve similar tumor control but the incidence of GVHD was not significantly increased after DLI.  相似文献   
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