“Objectives: This study aimed to develop and pilot an equi

“Objectives: This study aimed to develop and pilot an equity lens that could help researchers in developing a more equity-oriented approach toward priority setting and agenda setting in systematic reviews.

Study Design and Setting: We developed an equity lens to guide the development and evaluation of a prioritization process and evaluate its outcomes based on the information derived from a discussion workshop and a comparison with the existing literature on the topic. We piloted the process section of the equity lens across the 13 structured priority-setting approaches in the Cochrane


Results: We devised an equity lens with two checklists: one to guide P5091 the process of priority setting (nine questions) and the other to evaluate the outcomes of priority setting (eight questions). Of the nine questions, seven questions were partially addressed by at least one of the prioritization projects. Two questions were not considered in any of them. The prioritization projects did not report sufficient outcome data, thus we could not explore the eight question on evaluating outcomes.

Conclusion: Currently, there are few strategies in the Cochrane

Collaboration that explicitly address the research priorities of individuals from different sociodemographic groups. The equity lens for priority setting and agenda setting can help project teams to develop a more equity-oriented WH-4-023 datasheet approach to set a research agenda and/or prioritize research topics. However, further studies are needed to evaluate its impact on the prioritization process. (C) 2013 Elsevier Inc. All rights reserved.”
“The chemical composition of the lipophilic and phenolic extractives of the leaves, stems and roots of the salt marsh plant Halimione portulacoides from the Aveiro Lagoon was thoroughly investigated by gas chromatography-mass spectrometry

(GC-MS) and ultra-high-performance liquid chromatography-mass spectrometry (UHPLC-MS), respectively. The lipophilic fraction of leaves and stems is mainly composed of long chain aliphatic acids and alcohols (both in the C16-C30 range) and smaller amounts of sterols, such as schottenol, beta-sitosterol selleck kinase inhibitor and beta-sitostanol. The major component of roots extract is a triterpenic ketone, hop-17(21)-en-3-one, accounting for 2.8 g kg(-1) of dry material. Furthermore, thirteen phenolic compounds were firstly reported as constituents of this halophytic shrub. Among the studied plant tissues, leaves are the richest in phenolic compounds with 4.6 g kg(-1) of dry material, most of which correspond to sulfated flavonoids (3.1 g kg(-1) of dry material), particularly derivatives of isorhamnetin-sulfate. (C) 2013 Elsevier B.V. All rights reserved.”
“Purpose The so-called “”practical year”" is the last part of medical students’ education in Germany. Without being paid, final-year medical students have to work for 1 year under supervision in academic teaching hospitals.

Both formulations were well tolerated and there were no bleeding

Both formulations were well tolerated and there were no bleeding episodes. Conclusion: After a single-dose injection in healthy participants, anti-Xa activities of 2 formulations of LMWH enoxaparin were comparable. No significant difference was observed in the mean plasma aPTT. It remains to be seen whether the 2 formulations would show comparable clinical efficacy.”

case report describes a 10-year-old female patient with an adenomatoid odontogenic tumor developing together with a cystic complex odontoma. This occurrence is considered selleck chemicals very unusual. Immunohistochemical detection of cytokeratins AE1/AE3, CK5, CK8, CK10, CK14, CK19 and Ki-67 was performed. (Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2009; 108: e25-e29)”
“Patients undergoing major orthopedic surgery are at high venous thromboembolism (VTE) risk, with morbid and potentially fatal consequences. Anticoagulant VTE prophylaxis reduces rates of postoperative deep vein thrombosis by up to 60% to 70% in these patients. Therefore, pharmacological prophylaxis with low-molecular-weight heparins

(LMWHs), vitamin K antagonists, or fondaparinux is recommended by current guidelines. However, there remains an ongoing debate regarding when to initiate and the optimal duration for prophylaxis. Here, we discuss the mechanisms underlying thrombus formation in patients undergoing major orthopedic surgery, and we review the current literature on the benefit-to-risk ratio associated with preoperative and postoperative initiation of thromboprophylaxis NSC 649890 HCl and also the benefit-to-risk ratio in cases of neuraxial anesthesia. We also discuss the duration of postoperative VTE risk following major orthopedic surgery and assess the

“”critical thrombosis period”" when prophylaxis should be provided. Current literature reflects the need to balance the improved efficacy of initiating prophylaxis close to the surgery with increased risk of perioperative https://www.selleckchem.com/products/dihydrotestosterone.html bleeding. Evidence from pathology, epidemiology, and clinical studies suggests the risk period for VTE begins at surgery and extends well beyond hospitalization-a crucial issue when considering how long to give prophylaxis-and, in the case of total hip arthroplasty, for at least 3 months after surgery. Literature supports the greater use of “”just-in-time”" thromboprophylaxis initiation and after-discharge continuation of optimal prophylaxis in orthopedic surgery patients. Providing optimal thromboprophylaxis throughout the critical thrombosis period where a patient is at VTE risk will ensure the best reductions in VTE-related morbidity and mortality.”
“Objective. The aim of this study was to investigate whether radiopaque Portland cement (RPC) facilitates the mineralization process in human dental pulp cells (HDPCs) compared with pure Portland cement (PC).

Study design. Under a scanning electron microscope (SEM), cellular morphology was evaluated.

01) mass at d 130 Jejunal RNA and protein concentrations were le

01) mass at d 130. Jejunal RNA and protein concentrations were less (P = 0.07) and DNA was unaffected (P = 0.43) in Control-fed compared with High-fed ewes. Stage of gestation did not affect jejunal RNA, DNA (mg/g), or protein concentrations. Jejunal cellular proliferation was not affected by diet or stage of gestation. In jejunal mucosal tissue, MAPK Inhibitor Library chemical structure capillary number decreased, whereas capillary surface density and area per capillary increased (P = 0.01) with advancing pregnancy (d 50 vs. d 130), but were

independent of diet. Data indicated that intestinal mass as a proportion of maternal BW declined in overnourished, gestating ewe lambs. This response was more pronounced during late gestation and is likely explained by the increasing maternal BW Wortmannin order and adiposity rather than by the changing cellularity or cell proliferation.”
“Aim: The combination of a taxane and capecitabine offers synergistic antitumor activity. This study aimed to determine the efficacy and tolerability of a paclitaxel and capecitabine combination in Thai patients with metastatic breast cancer (MBC) not previously treated for metastatic disease.

Methods: This open-label,

single-center, non-comparative phase II study was conducted between December 2006 and March 2009. In all 40 MBC patients were treated with oral capecitabine 1000 mg/m(2) twice daily on days 1 to 14, and weekly paclitaxel 80 mg/m(2) in a 3-week cycle for a total of six cycles.

Results: After a median follow up of 13.4 months, an overall objective LDN-193189 response rate of 80%, with a partial response of 74% and a complete response of 5% were achieved. While 8% of patients achieved stable disease, 13% had progressive disease. Median time to progress was 8 months and median overall

survival was 24.4 months. One patient discontinued because of hypersensitivity to paclitaxel. There was no grade 4 toxicity. Skin and nail toxicity was found in 75% of patients (with 25% in grade 2 or 3), followed by neutropenia (45% in all with 15% in grades 2 or 3), neuropathy (25% in total with 5% in grade 2) and stomatitis and diarrhea (in both of which 5% experienced grade 1 severity).

Conclusion: A first-line regimen of weekly paclitaxel plus capecitabine is effective and tolerable in Thai MBC patients.”
“Purpose: To investigate the differences in the extracranial venous system in patients with multiple sclerosis (MS) and healthy control (HC) subjects by using magnetic resonance (MR) venography.

Materials and Methods: This HIPAA-compliant, prospective study was approved by the local institutional review board, and all participants gave informed consent. Fifty-seven patients, 41 (72%) with relapsing-remitting MS and 16 (28%) with secondary-progressive MS, and 21 HC subjects were imaged with a 3-T MR unit by using two-dimensional (2D) time-of-flight (TOF) and three-dimensional (3D) time-resolved imaging of contrast kinetics (TRICKS) sequences.

Urologists can use this nomogram to better inform patients of the

Urologists can use this nomogram to better inform patients of the potential need for epididymovasostomy and whether specialist referral is needed.”
“The neuregulin 1 (NRG1) receptor ErbB4 is involved in the development of cortical inhibitory GABAergic circuits and NRG1-ErbB4 signaling has been implicated in schizophrenia (SCZ). A magnetic resonance spectroscopy (H-1-MRS) study has demonstrated that a single-nucleotide polymorphism in ERBB4, rs7598440, influences human cortical GABA concentrations. Other work has highlighted the significant impact of this genetic variant on

expression of ERBB4 in the hippocampus and dorsolateral Selleck ZD1839 prefrontal cortex in human post mortem tissue. Our aim was to examine the association of rs7598440 with cerebrospinal fluid (CSF) GABA levels in healthy volunteers (n = 155). We detected a significant Selleck Epacadostat dose-dependent association of the rs7598440 genotype with CSF GABA levels (G-allele standardized beta = -0.23; 95% CIs: -0.39 to -0.07; P=0.0066). GABA concentrations were highest in A homozygous, intermediate in heterozygous, and lowest in G homozygous subjects. When excluding subjects on psychotropic medication (three subjects using antidepressants), the results did not change (G-allele standardized beta=-0.23; 95% CIs: -0.40

to -0.07; P=0.0051). The explained variance in CSF GABA by rs7598440 in our model is 5.2% (P=0.004). The directionality of our findings agrees with the aforementioned H-1-MRS and gene expression studies. Our observation therefore strengthens the evidence that the A-allele of rs7598440 in ERBB4 is associated with increased GABA concentrations in the human central nervous Milciclib research buy system (CNS). To our knowledge, our finding constitutes the first confirmation that CSF can be used to study genotype-phenotype correlations of GABA levels in the CNS. Such quantitative genetic analyses may be extrapolated to other CSF constituents relevant to SCZ in future studies. Neuropsychopharmacology (2012) 37, 2088-2092; doi:10.1038/npp.2012.57; published online

2 May 2012″
“Nanomedicine, or medicine using nanometric devices, has emerged in the past decade as an exhilarating domain that can help to solve a number of problems linked to unsatisfactory therapeutic responses of so-called ‘old drugs’. This dissatisfaction stems from inadequate biodistribution after a drug’s application, which leads to a limited therapeutic response but also to numerous side effects to healthy organs. The biodistribution of drugs encapsulated in a nanoobject that will act as a vector can be modified to tune its therapeutic efficacy. This review provides a general overview of existing colloidal nanovectors: liposomes, polymeric micelles, polymeric vesicles, polymeric nanoparticles (NPs), and dendrimers. We describe their characteristics, advantages and drawbacks, and discuss their use in the treatment of various diseases.

Responses to noxious heat were

Responses to noxious heat were selleck kinase inhibitor unaffected by 10% CA and menthol regardless of the order of chemical presentation. These data indicate that superficial Vc neurons receive convergent input from primary afferents expressing TRPM8 and TRPA1. The mutual cross-desensitization between CA and menthol, and differential modulation of cold- vs. heat-evoked responses, suggests a direct inhibition of TRPM8 and TRPA1 expressed in peripheral nerve endings by CA and menthol,

respectively, rather than a central site of interaction. (c) 2007 Elsevier Ireland Ltd. All rights reserved.”
“The role of the alpha 4 beta 2* nicotinic acetylcholine receptors (nAChR) in tobacco addiction in humans is largely unresolved. We visualized brain alpha 4 beta 2* nicotinic

PX-478 molecular weight acetylcholine receptors of smokers and non-smokers with positron emission tomography using 2-[F-18]fluoro-3-(2(S)azetidinylmethoxy)pyridine, commonly known as 2-[F-18]F-A-85380. The total brain distribution volume of 2-[F-18]F-A-85380 was significantly increased in smokers. Statistical parametric mapping revealed that the most prominent regional differences of distribution volumes (DV) were found in cerebellum and brainstem with an increased uptake in smokers. The up-regulation of alpha 4 beta 2* nAChR upon chronic nicotine exposure via tobacco smoking incorporates Selleckchem MK-0518 subcortical brain regions which may play an important role in nicotine addiction. (c) 2007 Elsevier Ireland Ltd. All rights reserved.”
“[C-11]Raclopride ([C-11]RAC) is a selective dopamine D-2/D-3 antagonist that is commonly used in positron emission tomography (PET) studies to assess both basal levels of receptor availability and changes in availability caused by alterations in striatal dopamine concentration. When designing [C-11]RAC studies, it is important to understand what variables may affect the results. Here, we examined differences in baseline striatal [C-11]RAC binding

potential (BPND) under two different “”rest”" conditions. Thirteen subjects received [C-11]RAC scans. Eight subjects were aware prior to initiation of scanning that they would receive a “”baseline”" scan, and that no additional procedures would take place during the scan (“”certain rest”" group, CER). Five subjects were informed that they might or might not receive an IV alcohol infusion during the scan (“”uncertain rest”" group, UNC). This group was informed five min after scan start that they would not receive alcohol. Voxel-wise analyses of binding potential (BPND) images generated for both “”rest”" conditions indicated that receptor availability was higher in UNC than in CER. This result was confirmed by a region-of-interest analysis, which indicated that the average BPND in right and left putamen was statistically higher in UNC.

These results demonstrate that dieldrin and lindane work cooperat

These results demonstrate that dieldrin and lindane work cooperatively to

induce DA neurotoxicity through the induction of oxidative stress and mitochondria! dysfunction. These findings may advance understanding of the role of pesticides in the multi-factorial etiology of PD. (C) 2009 Elsevier Inc. All rights reserved.”
“In view of selleck products the low loads of beta human papillomaviruses in skin samples, amounts of cellular DNA used in qualitative PCR may become limiting for virus detection and introduce variations in prevalence and multiplicity. This issue was explored within the context of a multicentre study and increasing prevalence and multiplicity was found with increasing input amounts of cellular DNA extracted from hair bulbs. To improve the quality and comparability between different epidemiologic studies ideally equal amounts of cellular DNA should be employed. When cellular DNA input varies this should be clearly taken into account in assessing viral prevalence and multiplicity. (C) 2009 Elsevier B.V. All rights reserved.”

our environment, mammals (including humans) are exposed to various types of ionizing radiation and both persistent and non-persistent toxic chemicals. It is known that ionizing radiation, as well as methyl mercury, can induce neurotoxicological and neurobehavioural effects in mammals. These developmental neurotoxic effects can be seen following exposure during gestation. There is a lack of knowledge concerning the effects and consequences of low-dose exposure during critical Selumetinib clinical trial phases of pen natal and/or neonatal brain development, and of the combination of ionizing radiation and environmental chemicals. A recent study has indicated that low doses of ionizing radiation to the

human brain during infancy influence cognitive ability in adulthood. In the present study, 10-day old neonatal male NMRI mice were exposed to a single oral dose of MeHg (0.40 or 4.0 mg/kg bw). Four hours after the MeHg exposure the mice were subjected to (60)Co gamma-radiation on one occasion at doses of 0.2 and www.selleck.cn/products/gdc-0994.html 0.5 Gy. The animals were then subjected to a spontaneous behaviour test at 2 and 4 months, and a water maze test at the age of 5 months. Neither the single dose of MeHg (0.4 mg/kg bw) nor the radiation dose of 0.2 Gy affected their spontaneous behaviour, whereas the co-exposure to external gamma-radiation and MeHg caused developmental neurotoxic effects. The study shows that gamma-radiation and MeHg can interact and significantly exacerbate developmental neurotoxic effects, as manifested by disrupted spontaneous behaviour, lack of habituation, and impaired learning and memory functions. (C) 2010 Elsevier Inc. All rights reserved.

07 vital genome copies/ml in one-step real-time RT-PCR or 7 x 10(

07 vital genome copies/ml in one-step real-time RT-PCR or 7 x 10(-16) viral genome copies/ml in a nested real-time PCR. WNV could be identified and typed in serum and brain specimens from a human and horse with neurological disease. To our knowledge, this is the first assay designed for the simultaneous detection and genotyping of WNV by rapid, sensitive real-time PCR which may be implemented in diagnostic and

epidemiology laboratories. (C) 2008 Elsevier B.V. All rights reserved.”
“The present study investigated the course of visual searching to a target in a fixed location, using an emotional flanker task. Event-related potentials (ERPs) were recorded while participants performed the task. Emotional facial expressions selleck compound were used as emotion-eliciting triggers. The course of visual searching was analyzed through the emotional effects arising from these emotion-eliciting stimuli. The flanker stimuli showed effects at about 150-250 ms following the stimulus onset, while the effect of target stimuli showed effects at about 300-400 ms. The visual search sequence in an emotional flanker task moved from a whole overview to a specific target, even if the target always appeared at a known location. The processing sequence

was “”parallel”" in this task. The results supported the feature integration theory of visual search. (C) 2009 LY3039478 mw Elsevier Ireland Ltd. All rights reserved.”
“Four IgG(1K) monoclonal antibodies (mAbs) against Influenza A/Chicken/Vietnam/8/2004 (H5N1) virus are described. Three of these showed neutralizing activities against H5N1 strains from clades 1. 2 and 3 using a retroviral pseudotype or live virus microneutralization assay. In the pseudotype assay, the IC(90) neutralizing titre range was >1600-51,200, and with the microneutralization was 80

> 10,240, MAb 1C1 showed strong neutralizing activities in both assays. All four mAbs reacted specifically to the immunogen by immunohistochemical staining and to A/Hong Kong/483/1997 (H5N1) and A/Thailand/1(KAN-1)/2004 (H5N1)-infected MDCK cells by immunofluorescence. Selleckchem SGC-CBP30 ELISA titrations of the mAbs showed specificity for H5N1 haemagglutinin (HA) and no cross-reactivity to 15 other Influenza A subtypes. Only mAbs 1C1 and the non-neutralizing 1F7 reacted with HA(1), the cleaved subunit of HA, by Western blot. These results suggest that the mAbs recognize distinct or overlapping epitopes and will be useful reagents for construction of specific rapid point-of-care assays or for therapeutic use. Crown Copyright (C) 2008 Published by Elsevier B.V. All rights reserved.”
“We used functional MRI (fMRI) and a network model based on graph theory to measure functional connectivity of brain motor network in the resting state in patients with Parkinson’s disease (PD). FMRIs were acquired in 22 PD patients before and after levodopa administration, and in age- and sex-matched normal controls.

Clinical findings in these animals strongly resemble clinical fin

Clinical findings in these animals strongly resemble clinical findings in CRPS, and can be prevented by anticytokine and anti-neuropeptide treatment. In Dinaciclib in vivo CRPS patients, there is meanwhile also plenty of evidence that neurogenic inflammation contributes to clinical presentation. Increased cytokine production was demonstrated, as well as facilitated neurogenic inflammation.

Very recently even “”non-inflammatory”" signs of CRPS (hyperhidrosis, cold skin) have been linked to neuropeptide signaling. Surprisingly, there was even moderately increased neurogenic inflammation in unaffected body regions. This favors the possibility that CRPS patients share genetic similarities. The future search for genetic commonalities will help us to further

unravel the “”mystery”" CRPS. (C) 2008 Elsevier Ireland Ltd. All rights reserved.”
“Purpose: Functional and structural lesions of ureteral endings seem to alter the active valve mechanism of the ureterovesical junction, causing vesicoureteral reflux. The interaction of the dystroglycan complex with components of the extracellular matrix may have an important role in force transmission and sarcolemma protection, and the sarcoglycan complex is an essential component of the muscle membrane located dystroglycan complex. We performed immunofluorescence and molecular analysis on the expression of sarcoglycan complex subunits.

Materials and Methods: A total of 21 specimens of refluxing Staurosporine research buy Daporinad research buy ureteral endings were obtained during ureteral reimplantation. Six ureteral ends obtained during organ explantation were used as controls. Immunohistochemical analysis and reverse transcriptase polymerase chain reaction evaluation were performed for

alpha, beta, gamma, delta and epsilon-sarcoglycan complex.

Results: The Spearman test revealed a significant positive correlation between alpha-sarcoglyean complex immunofluorescence intensity and grade of vesicoureteral reflux, while a negative correlation was recorded between epsilon-sareoglyean complex immunofluorescence intensity and grade of vesicoureteral reflux.

Conclusions: Semiquantitative analysis demonstrated a significant grade related impairment of epsilon-sarcoglycan complex coupled with an increased expression of a-sarcoglyean complex. This observation suggests that the structural deficiency of the trigonal ureterovesical junction could cause a passive stretching of refluxing urine on the ureter, deranging the multimodular tensegrity architecture of the sarcoglycan subcomplex, or that the sarcoglycan complex could have a key role in the physiopathology of vesicoureteral reflux. In fact, the defect in any of the sarcoglycan complexes results in degeneration of membrane integrity and muscle fiber. An altered configuration of the sarcoglycan complex could explain the structural and functional changes in refluxing ureteral endings.

(J Vase Surg 2012;55:24-32 )”
“Benzodiazepines (BZs) are eff

(J Vase Surg 2012;55:24-32.)”
“Benzodiazepines (BZs) are effective anxiolytics and hypnotics, but their use is limited by unwanted side effects, such as motor impairment.

To assess the contribution of alpha 1 subunit-containing gamma-aminobutyric acid(A) (GABA(A)) receptor subtypes to the motor-impairing effects of BZs, the present study evaluated two observable measures of motor coordination (balance on a pole, resistance to hind-limb flexion) engendered by nonselective and selective BZ-site agonists in squirrel monkeys.

Multiple doses of nonselective

BZs (triazolam, alprazolam, diazepam, and chlordiazepoxide) and alpha 1 subunit-preferring agonists (zolpidem and zaleplon) were administered to adult male squirrel monkeys (N = 4-6), and experimenters rated the monkey’s ability to balance on a horizontal pole (“”ataxic-like effects”"), as well as the degree of BI 2536 molecular weight resistance to hind-limb flexion (“”myorelaxant-like Navitoclax in vivo effects”").

Administration of all BZ-type drugs resulted in ataxic-like and myorelaxant-like effects. Pretreatment with the alpha 1 subunit-preferring antagonist beta-carboline-3-carboxylate-t-butyl ester (beta CCT) attenuated the ataxic-like effects engendered by both types of drugs. However, beta CCT was largely ineffective at blocking the ability of both BZs and non-BZs to induce myorelaxant-like effects.

These experiments demonstrate dose-dependent motor impairment

in squirrel monkeys using quantitative behavioral observation techniques. Altogether, these findings suggest a lack of a prominent role for alpha 1 subunit-containing receptors in the alteration of hind-limb flexion, a putative measure of myorelaxation, induced by BZ-type drugs in monkeys.”

the mammalian CNS, excessive release of glutamate and overactivation of glutamate receptors are responsible for the Tucidinostat clinical trial secondary (delayed) neuronal death following neuronal injury, including ischemia, traumatic brain injury (TBI) and epilepsy. Recent studies in mice showed a critical role for neuronal gap junctions in NMDA receptor-mediated excitotoxicity and ischemia-mediated neuronal death. Here, using controlled cortical impact (CCI) in adult mice, as a model of TBI, and Fluoro-jade B staining for analysis of neuronal death, we set to determine whether neuronal gap junctions play a role in the CCI-mediated secondary neuronal death. We report that 24 h post-CCI, substantial neuronal death is detected in a number of brain regions outside the injury core, including the striatum. The striatal neuronal death is reduced both in wild-type mice by systemic administration of mefloquine (a relatively selective blocker of neuronal gap junctions) and in knockout mice lacking connexin 36 (neuronal gap junction protein). It is also reduced by inactivation of group II metabotropic glutamate receptors (with LY341495) which, as reported previously, control the rapid increase in neuronal gap junction coupling following different types of neuronal injury.

5-10 mg/kg, i p ; JNJ16567083)

Results In DNMTP task,

5-10 mg/kg, i.p.; JNJ16567083).

Results In DNMTP task, EMQMCM produced delay-dependent increases in performance accuracy so that, at 10 mg/kg dose level, percentage of correct lever choices was enhanced at 8- and 16-s delays. In DRL task, at all three

tested doses, response rates were higher, and reinforcement rates were lower than under control conditions. In signal duration discrimination tasks, EMQMCM did not have any specific effects on temporal control. In tolerance to delay of reward, EMQMCM (5 and 10 mg/kg) facilitated choice of the lever associated with large reward at longer delay levels.

Conclusions Blockade of mGlu1 receptors improves working memory and reduces impulsive choice at the doses that have no effects on time perception but appear to facilitate impulsive action.”

has been shown to impact on learning and memory in both humans and animals, https://www.selleckchem.com/products/Acadesine.html selleck chemicals but the downstream signaling mechanisms involved are poorly characterized. Insulin receptor substrate-2 (Irs2) is an adaptor protein that couples activation of insulin- and insulin- like growth factor-1 receptors to downstream signaling pathways. Here, we have deleted Irs2, either in the whole brain or selectively in the forebrain, using the nestin Cre- or D6 Cre-deleter mouse lines, respectively. We show that brain- and forebrain-specific Irs2 knockout mice have enhanced hippocampal spatial reference memory. Furthermore, NesCreIrs2KO mice

have enhanced spatial working memory and contextual- and cued-fear memory. Deletion of Irs2 in the brain also increases PSD-95 expression and the density of dendritic spines in RG7112 purchase hippocampal area CA1, possibly reflecting an increase in the number of excitatory synapses per neuron in the hippocampus that can become activated during memory formation. This increase in activated excitatory synapses might underlie the improved hippocampal memory formation observed in NesCreIrs2KO mice. Overall, these results suggest that Irs2 acts as a negative regulator on memory formation by restricting dendritic spine generation.”
“An increase in oxidative stress and overproduction of oxidizing reactive species plays an important role in the pathophysiology of several conditions encountered in the neurocritical care setting including: ischemic and hemorrhagic strokes, traumatic brain injury, acute respiratory distress syndrome, sepsis, and organ failure. The presence of oxidative stress in these conditions is supported by a large body of pre-clinical and clinical studies, and provides a rationale to support a potential therapeutic role for antioxidants. The purpose of this article is to briefly review the basic mechanisms and molecular biology of oxidative stress, summarize its role in critically ill neurological patients, and review available data regarding the potential role of antioxidant strategies in neurocritical care and future directions.