Spermidine Synthase Localization in Retinal Layers: Early Age Changes.

Polyamine (PA) spermidine (SPD) plays a crucial role in aging. Since SPD accumulates in glial cells, particularly in Müller retinal cells (MCs), the expression of the SPD-synthesizing enzyme spermidine synthase (SpdS) in Müller glia and age-dependent SpdS activity are not known. We used immunocytochemistry, Western blot (WB), and image analysis on rat retinae at postnatal days 3, 21, and 120. The anti-glutamine synthetase (GS) antibody was used to identify glial cells. In the neonatal retina (postnatal day 3 (P3)), SpdS was expressed in almost all progenitor cells in the neuroblast. However, by day 21 (P21), the SpdS label was pronouncedly expressed in multiple neurons, while GS labels were observed only in radial Müller glial cells. During early cell adulthood, at postnatal day 120 (P120), SpdS was observed solely in ganglion cells and a few other neurons. Western blot and semi-quantitative analyses of SpdS labeling showed a dramatic decrease in SpdS at P21 and P120 compared to P3. In conclusion, the redistribution of SpdS with aging indicates that SPD is first synthesized in all progenitor cells and then later in neurons, but not in glia. However, MCs take up and accumulate SPD, regardless of the age-associated decrease in SPD synthesis in neurons.

Implementation of esophageal endoscopic submucosal dissection in Spain: Results from the nationwide registry. / Implementación de la disección endoscópica submucosa esofágica en España: resultados del registro nacional.

INTRODUCTION AND AIMS: The outcomes of endoscopic submucosal dissection (ESD) in the esophagus have not been assessed in our country. Our primary aim was to analyze the effectiveness and safety of the technique. MATERIAL AND METHODS: Analysis of the prospectively maintained national registry of ESD. We included all superficial esophageal lesions removed by ESD in 17 hospitals (20 endoscopists) between January 2016 and December 2021. Subepithelial lesions were excluded. The primary outcome was curative resection. We conducted a survival analysis and used logistic regression analysis to assess predictors of non-curative resection. RESULTS: A total of 102 ESD were performed on 96 patients. The technical success rate was 100% and the percentage of en-bloc resection was 98%. The percentage of R0 and curative resection was 77.5% (n=79; 95%CI: 68%-84%) and 63.7% (n=65; 95%CI: 54%-72%), respectively. The most frequent histology was Barrett-related neoplasia (n=55 [53.9%]). The main reason for non-curative resection was deep submucosal invasion (n=25). The centers with a lower volume of ESD obtained worse results in terms of curative resection. The rate of perforation, delayed bleeding and post-procedural stenosis were 5%, 5% and 15.7%, respectively. No patient died or required surgery due to an adverse effect. After a median follow-up of 14months, 20patients (20.8%) underwent surgery and/or chemoradiotherapy, and 9 patients died (mortality 9.4%). CONCLUSIONS: In Spain, esophageal ESD is curative in approximately two out of three patients, with an acceptable risk of adverse events.

Ketamine as a pharmacological tool for the preclinical study of memory deficit in schizophrenia.

Schizophrenia is a serious neuropsychiatric disorder characterized by the presence of positive symptoms (hallucinations, delusions, and disorganization of thought and language), negative symptoms (abulia, alogia, and affective flattening), and cognitive impairment (attention deficit, impaired declarative memory, and deficits in social cognition). Dopaminergic hyperactivity seems to explain the positive symptoms, but it does not completely clarify the appearance of negative and cognitive clinical manifestations. Preclinical data have demonstrated that acute and subchronic treatment with NMDA receptor antagonists such as ketamine (KET) represents a useful model that resembles the schizophrenia symptomatology, including cognitive impairment. This latter has been explained as a hypofunction of NMDA receptors located on the GABA parvalbumin-positive interneurons (near to the cortical pyramidal cells), thus generating an imbalance between the inhibitory and excitatory activity in the corticomesolimbic circuits. The use of behavioral models to explore alterations in different domains of memory is vital to learn more about the neurobiological changes that underlie schizophrenia. Thus, to better understand the neurophysiological mechanisms involved in cognitive impairment related to schizophrenia, the purpose of this review is to analyze the most recent findings regarding the effect of KET administration on these processes.

Biological and Clinical Implications of Sex-Specific Differences in Alzheimer's Disease.

Mounting evidence indicates that the female sex is a risk factor for Alzheimer's disease (AD), the most common cause of dementia worldwide. Decades of research suggest that sex-specific differences in genetics, environmental factors, hormones, comorbidities, and brain structure and function may contribute to AD development. However, although significant progress has been made in uncovering specific genetic factors and biological pathways, the precise mechanisms underlying sex-biased differences are not fully characterized. Here, we review several lines of evidence, including epidemiological, clinical, and molecular studies addressing sex differences in AD. In addition, we discuss the challenges and future directions in advancing personalized treatments for AD.

Co-Expression Network Analysis Identifies Molecular Determinants of Loneliness Associated with Neuropsychiatric and Neurodegenerative Diseases.

Loneliness and social isolation are detrimental to mental health and may lead to cognitive impairment and neurodegeneration. Although several molecular signatures of loneliness have been identified, the molecular mechanisms by which loneliness impacts the brain remain elusive. Here, we performed a bioinformatics approach to untangle the molecular underpinnings associated with loneliness. Co-expression network analysis identified molecular 'switches' responsible for dramatic transcriptional changes in the nucleus accumbens of individuals with known loneliness. Loneliness-related switch genes were enriched in cell cycle, cancer, TGF-ß, FOXO, and PI3K-AKT signaling pathways. Analysis stratified by sex identified switch genes in males with chronic loneliness. Male-specific switch genes were enriched in infection, innate immunity, and cancer-related pathways. Correlation analysis revealed that loneliness-related switch genes significantly overlapped with 82% and 68% of human studies on Alzheimer's (AD) and Parkinson's diseases (PD), respectively, in gene expression databases. Loneliness-related switch genes, BCAM, NECTIN2, NPAS3, RBM38, PELI1, DPP10, and ASGR2, have been identified as genetic risk factors for AD. Likewise, switch genes HLA-DRB5, ALDOA, and GPNMB are known genetic loci in PD. Similarly, loneliness-related switch genes overlapped in 70% and 64% of human studies on major depressive disorder and schizophrenia, respectively. Nine switch genes, HLA-DRB5, ARHGAP15, COL4A1, RBM38, DMD, LGALS3BP, WSCD2, CYTH4, and CNTRL, overlapped with known genetic variants in depression. Seven switch genes, NPAS3, ARHGAP15, LGALS3BP, DPP10, SMYD3, CPXCR1, and HLA-DRB5 were associated with known risk factors for schizophrenia. Collectively, we identified molecular determinants of loneliness and dysregulated pathways in the brain of non-demented adults. The association of switch genes with known risk factors for neuropsychiatric and neurodegenerative diseases provides a molecular explanation for the observed prevalence of these diseases among lonely individuals.

Epigenetic Factors and ncRNAs in Testicular Cancer.

Testicular cancer is the most prevalent tumor among males aged 15 to 35, resulting in a significant number of newly diagnosed cases and fatalities annually. Non-coding RNAs (ncRNAs) have emerged as key regulators in various cellular processes and pathologies, including testicular cancer. Their involvement in gene regulation, coding, decoding, and overall gene expression control suggests their potential as targets for alternative treatment approaches for this type of cancer. Furthermore, epigenetic modifications, such as histone modifications, DNA methylation, and the regulation by microRNA (miRNA), have been implicated in testicular tumor progression and treatment response. Epigenetics may also offer critical insights for prognostic evaluation and targeted therapies in patients with testicular germ cell tumors (TGCT). This comprehensive review aims to present the latest discoveries regarding the involvement of some proteins and ncRNAs, mainly miRNAs and lncRNA, in the epigenetic aspect of testicular cancer, emphasizing their relevance in pathogenesis and their potential, given the fact that their specific expression holds promise for prognostic evaluation and targeted therapies.

Electronic Medication Reconciliation Tools Aimed at Healthcare Professionals to Support Medication Reconciliation: a Systematic Review.

The development of health information technology available and accessible to professionals is increasing in the last few years. However, a low number of electronic health tools included some kind of information about medication reconciliation. To identify all the electronic medication reconciliation tools aimed at healthcare professionals and summarize their main features, availability, and clinical impact on patient safety. A systematic review of studies that included a description of an electronic medication reconciliation tool (web-based or mobile app) aimed at healthcare professionals was conducted. The review protocol was registered with PROSPERO: registration number CRD42022366662, and followed PRISMA guidelines. The literature search was performed using four healthcare databases: PubMed, EMBASE, Cochrane Library, and Scopus with no language or publication date restrictions. We identified a total of 1227 articles, of which only 12 met the inclusion criteria.Through these articles,12 electronic tools were detected. Viewing and comparing different medication lists and grouping medications into multiple categories were some of the more recurring features of the tools. With respect to the clinical impact on patient safety, a reduction in adverse drug events or medication discrepancies was detected in up to four tools, but no significant differences in emergency room visits or hospital readmissions were found. 12 e-MedRec tools aimed at health professionals have been developed to date but none was designed as a mobile app. The main features that healthcare professionals requested to be included in e-MedRec tools were interoperability, "user-friendly" information, and integration with the ordering process.

Optimized Surveillance Intervals Following Endoscopic Eradication of Dysplastic Barrett's Esophagus: An International Cohort Study.

BACKGROUND & AIMS: Recommended surveillance intervals after complete eradication of intestinal metaplasia (CE-IM) after endoscopic eradication therapy (EET) are largely not evidence-based. Using recurrence rates in a multicenter international Barrett's esophagus (BE) CE-IM cohort, we aimed to generate optimal intervals for surveillance. METHODS: Patients with dysplastic BE undergoing EET and achieving CE-IM from prospectively maintained databases at 5 tertiary-care centers in the United States and the United Kingdom were included. The cumulative incidence of recurrence was estimated, accounting for the unknown date of actual recurrence that lies between the dates of current and previous endoscopy. This cumulative incidence of recurrence subsequently was used to estimate the proportion of patients with undetected recurrence for various surveillance intervals over 5 years. Intervals were selected that minimized recurrences remaining undetected for more than 6 months. Actual patterns of post-CE-IM follow-up evaluation are described. RESULTS: A total of 498 patients (with baseline low-grade dysplasia, 115 patients; high-grade dysplasia [HGD], 288 patients; and intramucosal adenocarcinoma [IMCa], 95 patients) were included. Any recurrence occurred in 27.1% and dysplastic recurrence occurred in 8.4% over a median of 2.6 years of follow-up evaluation. For pre-ablation HGD/IMCa, intervals of 6, 12, 18, and 24 months, and then annually, resulted in no patients with dysplastic recurrence undetected for more than 6 months, comparable with current guideline recommendations despite a 33% reduction in the number of surveillance endoscopies. For pre-ablation low-grade dysplasia, intervals of 1, 2, and 4 years balanced endoscopic burden and undetected recurrence risk. CONCLUSIONS: Lengthening post-CE-IM surveillance intervals would reduce the endoscopic burden after CE-IM with comparable rates of recurrent HGD/IMCa. Future guidelines should consider reduced surveillance frequency.

Preserving the woody plant tree of life in China under future climate and land-cover changes.

The tree of life (TOL) is severely threatened by climate and land-cover changes. Preserving the TOL is urgent, but has not been included in the post-2020 global biodiversity framework. Protected areas (PAs) are fundamental for biological conservation. However, we know little about the effectiveness of existing PAs in preserving the TOL of plants and how to prioritize PA expansion for better TOL preservation under future climate and land-cover changes. Here, using high-resolution distribution maps of 8732 woody species in China and phylogeny-based Zonation, we find that current PAs perform poorly in preserving the TOL both at present and in 2070s. The geographical coverage of TOL branches by current PAs is approx. 9%, and less than 3% of the identified priority areas for preserving the TOL are currently protected. Interestingly, the geographical coverage of TOL branches by PAs will be improved from 9% to 52-79% by the identified priority areas for PA expansion. Human pressures in the identified priority areas are high, leading to high cost for future PA expansion. We thus suggest that besides nature reserves and national parks, other effective area-based conservation measures should be considered. Our study argues for the inclusion of preserving the TOL in the post-2020 conservation framework, and provides references for decision-makers to preserve the Earth's evolutionary history.

The 5-HT6R agonist E-6837 and the antagonist SB-271046 reverse the psychotic-like behaviors induced by ketamine.

Schizophrenia is a serious mental disorder that affects 1% of the world's population. Although various therapeutic tools have been developed since the appearance of the first generation of antipsychotics, the effect of these agents does not manage to attenuate a significant part of psychotic symptoms. Ketamine is an anesthetic agent able to produce psychotic-like symptoms through the antagonism of the glutamatergic N-methyl-d-aspartic acid (NMDA) receptors (NMDARs). This drug has been widely used to study new pharmacological tools with potential antipsychotic properties. On the contrary, it is known that the 5-HT6 receptor agonist and antagonist drugs induce procognitive, anxiolytic and antidepressant effects in different preclinical models. Therefore, the aim of this study was to evaluate the behavioral actions of the 5-HT6 receptors' agonist E-6837 and the antagonist SB-271046, in ICR-CD1 mice previously treated with a subchronic ketamine scheme (10 mg/kg i.p. daily for 5 days). Results showed that repeated administration of ketamine induced recognition memory deficit, anxiogenic effects, obsessive-compulsive behaviors and stereotyped movements. The acute administration of both 5-HT6 agents reversed the memory deficit and induced a decrease in anxiety, whereas SB-271046 administration produced a decrease in climbing behavior. The injection of either of these 5-HT6 drugs had no effect in the light-dark test. Surprisingly, when these drugs were injected together with ketamine, anxiogenic actions were produced. Current findings suggest that both agonist and antagonist 5-HT6 drugs play an important role in modulating psychotic-like symptoms induced by the subchronic blockade of NMDAR.

Physical Activity Rewires the Human Brain against Neurodegeneration.

Physical activity may offset cognitive decline and dementia, but the molecular mechanisms by which it promotes neuroprotection remain elusive. In the absence of disease-modifying therapies, understanding the molecular effects of physical activity in the brain may be useful for identifying novel targets for disease management. Here we employed several bioinformatic methods to dissect the molecular underpinnings of physical activity in brain health. Network analysis identified 'switch genes' associated with drastic hippocampal transcriptional changes in aged cognitively intact individuals. Switch genes are key genes associated with dramatic transcriptional changes and thus may play a fundamental role in disease pathogenesis. Switch genes are associated with protein processing pathways and the metabolic control of glucose, lipids, and fatty acids. Correlation analysis showed that transcriptional patterns associated with physical activity significantly overlapped and negatively correlated with those of neurodegenerative diseases. Functional analysis revealed that physical activity might confer neuroprotection in Alzheimer's (AD), Parkinson's (PD), and Huntington's (HD) diseases via the upregulation of synaptic signaling pathways. In contrast, in frontotemporal dementia (FTD) its effects are mediated by restoring mitochondrial function and energy precursors. Additionally, physical activity is associated with the downregulation of genes involved in inflammation in AD, neurogenesis in FTD, regulation of growth and transcriptional repression in PD, and glial cell differentiation in HD. Collectively, these findings suggest that physical activity directs transcriptional changes in the brain through different pathways across the broad spectrum of neurodegenerative diseases. These results provide new evidence on the unique and shared mechanisms between physical activity and neurodegenerative diseases.

Synthesis of graphene oxide from agave fiberTequilana Weberby hydrothermal method.

Lignocellulosic residues are an important biomass source in Mexico, which can be considered as starting materials for obtaining carbon materials. In this work, carbon materials were produced by pyrolysis of agave fiber (AF). The results obtained revealed that the hydrothermal process was successfully used for the synthesis of carbon fibers and subsequently potentiate the production of graphite sheets and graphene oxide (GO), after determining and optimizing the reaction conditions. The formation of graphite and GO was indicated by XRD, Raman spectroscopy and TGA thermal analysis, the latter evaluated the carbon oxidation range. Scanning electron microscope showed the samples morphology and microstructure of the AFTequilana Weberand the synthesized products (Graphite-600 °C, GO-800 °C and GO-1000 °C), being all of them carbon allotropes, they presented size and variable thickness, with potential surface characteristics useful in various industrial applications. The hydrothermal and thermal processes were considered an economic and environmental way of obtaining materials under inert conditions, especially to produce GO, which is a material that has many useful properties and a plethora of new applications, like a more affordable support for catalysts, absorbent, semiconductor.

Magnetic resonance imaging diagnosis of a skeletal dysplasia mimicking erosive arthropathy.

This case report of a 14-year-old boy with arthralgia and clinically suspected inflammatory arthropathy highlights how magnetic resonance imaging (MRI) ultimately diagnosed skeletal dysplasia. A genetic evaluation revealed a transient receptor potential vanilloid 4 (TRPV4) pathogenic variant. This is a rare description of the MRI appearance of this type of dysplasia in long bone epiphyses corresponding with the histological findings of disrupted endochondral ossification. This report offers imaging support to the description of endochondral bone growth disruption in TRPV4-related skeletal dysplasias.

Network Analysis Identifies Sex-Specific Gene Expression Changes in Blood of Amyotrophic Lateral Sclerosis Patients.

Understanding the molecular mechanisms underlying the pathogenesis of amyotrophic lateral sclerosis (ALS), a devastating neurodegenerative disease, is a major challenge. We used co-expression networks implemented by the SWitch Miner software to identify switch genes associated with drastic transcriptomic changes in the blood of ALS patients. Functional analyses revealed that switch genes were enriched in pathways related to the cell cycle, hepatitis C, and small cell lung cancer. Analysis of switch genes by sex revealed that switch genes from males were associated with metabolic pathways, including PI3K-AKT, sphingolipid, carbon metabolism, FOXO, and AMPK signaling. In contrast, female switch genes related to infectious diseases, inflammation, apoptosis, and atherosclerosis. Furthermore, eight switch genes showed sex-specific gene expression patterns. Collectively, we identified essential genes and pathways that may explain sex differences observed in ALS. Future studies investigating the potential role of these genes in driving disease disparities between males and females with ALS are warranted.

Co-Adjuvant Therapy Efficacy of Catechin and Procyanidin B2 with Docetaxel on Hormone-Related Cancers In Vitro.

Prostate (PC) and breast cancer (BC) are heterogeneous hormonal cancers. Treatment resistance and adverse effects are the main limitations of conventional chemotherapy treatment. The use of sensitizing agents could improve the effectiveness of chemotherapeutic drugs as well as obviate these limitations. This study analyzes the effect of single catechin (CAT), procyanidin B2 (ProB2) treatment as well as the co-adjuvant treatment of each of these compounds with docetaxel (DOCE). We used PC- and BC-derived cell lines (PC3, DU-145, T47D, MCF-7 and MDA-MB-231). The short and long-term pro-apoptotic, anti-proliferative and anti-migratory effects were analyzed. RT-qPCR was used to discover molecular bases of the therapeutic efficacy of these compounds. ProB2 treatment induced a two- to five-fold increase in anti-proliferative and pro-apoptotic effects compared to single DOCE treatment, and also had a more sensitizing effect than DOCE on DU145 cells. Regarding BC cells, ProB2- and CAT-mediated sensitization to DOCE anti-proliferative and pro-apoptotic effects was cell-independent and cell-dependent, respectively. Combined treatment led to high-efficacy effects on MCF-7 cells, which were associated to the up-regulation of CDKN1A, BAX, caspase 9 and E-cadherin mRNA under combined treatment compared to single DOCE treatment. CAT and ProB2 can enhance the efficacy of DOCE therapy on PC and BC cells by the sensitizing mechanism.

Adapted Physical Education Teachers' Job Satisfaction.

Grounded in occupational socialization theory, the authors examined adapted physical education (APE) teachers' job satisfaction. Twelve (nine female and three male) APE teachers who had 3-43 years of teaching experience participated in the study. A semistructured interview was employed. The interviews focused on the participants' roles and responsibilities. The following questions guided this study: (a) What social agents positively impact APE teachers' job satisfaction? (b) what APE teachers' roles and responsibilities are related to job satisfaction? and (c) what type of working conditions are linked to APE teachers' job satisfaction? Thematic analysis was employed to analyze the data. The following four themes emerged from the analysis: (a) support from administrators, physical education teachers, and colleagues; (b) relevant and meaningful professional development; (c) itinerant working conditions; and (d) seeing students' progress and achievement. The results of this study provide several implications to enhance APE teachers' job satisfaction.

Clip Closure After Resection of Large Colorectal Lesions With Substantial Risk of Bleeding.

BACKGROUND & AIMS: It is not clear whether closure of mucosal defects with clips after colonic endoscopic mucosal resection (EMR) prevents delayed bleeding, although it seems to have no protective effects when risk is low. We performed a randomized trial to evaluate the efficacy of complete clip closure of large (≥2 cm) nonpedunculated colorectal lesions after EMR in patients with an estimated average or high risk of delayed bleeding. METHODS: We performed a single-blind trial at 11 hospitals in Spain from May 2016 through June 2018, including 235 consecutive patients who underwent EMR for large nonpedunculated colorectal lesions with an average or high risk of delayed bleeding (based on Spanish Endoscopy Society Endoscopic Resection Group score). Participants were randomly assigned to groups that received closure of the scar with 11-mm through-the-scope clips (treated, n = 119) or no clip (control, n = 116). The primary outcome was proportion of patients in each group with delayed bleeding, defined as evident hematochezia that required medical intervention within 15 days after colonoscopy. RESULTS: In the clip group, complete closure was achieved in 68 (57%) cases, with partial closure in 33 (28%) cases and failure to close in 18 (15%) cases. Delayed bleeding occurred in 14 (12.1%) patients in the control group and in 6 (5%) patients in the clip group (absolute risk difference, reduction of 7% in the clip group; 95% confidence interval, -14.7% to 0.3%). After completion of the clip closure, there was only 1 (1.5%) case of delayed bleeding (absolute risk difference, reduction of 10.6%; 95% confidence interval, -4.3% to 17.9%). CONCLUSIONS: In a randomized trial of patients with large nonpedunculated colorectal lesions undergoing EMR, we found that clip closure of mucosal defects in patients with a risk of bleeding can be a challenge, but also reduces delayed bleeding. Prevention of delayed bleeding required complete clip closure. ClinicalTrials.gov ID: NCT02765022.

Hypercytokinemia in COVID-19: Tear cytokine profile in hospitalized COVID-19 patients.

The aim of this study is to analyze the concentrations of cytokines in tear of hospitalized COVID-19 patients compared to healthy controls. Tear samples were obtained from 41 healthy controls and 62 COVID-19 patients. Twenty-seven cytokines were assessed: interleukin (IL)-1b, IL-1RA, IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IL9, IL-10, IL-12, IL-13, IL-15, IL-17, eotaxin, fibroblast growth factor basic, granulocyte colony-stimulating factor (G-CSF), granulocyte-monocyte colony-stimulating factor (GM-CSF), interferon (IFN)-γ, interferon gamma-induced protein, monocyte chemo-attractant protein-1, macrophage inflammatory protein (MIP)-1a, MIP-1b, platelet-derived growth factor (PDGF), regulated on activation normal T cell expressed and secreted, tumor necrosis factor-α and vascular endothelial growth factor (VEGF).In tear samples of COVID-19 patients, an increase in IL-9, IL-15, G-CSF, GM-CSF, IFN-γ, PDGF and VEGF was observed, along with a decrease in eotaxin compared to the control group (p < 0.05). A poor correlation between IL-6 levels in tear and blood was found. IL-1RA and GM-CSF were significantly lower in severe patients and those who needed treatment targeting the immune system (p < 0.05). Tear cytokine levels corroborate the inflammatory nature of SARS-CoV-2.

Clinical validation of risk scoring systems to predict risk of delayed bleeding after EMR of large colorectal lesions.

BACKGROUND AND AIMS: The Endoscopic Resection Group of the Spanish Society of Endoscopy (GSEED-RE) model and the Australian Colonic Endoscopic Resection (ACER) model were proposed to predict delayed bleeding (DB) after EMR of large superficial colorectal lesions, but neither has been validated. We validated and updated these models. METHODS: A multicenter cohort study was performed in patients with nonpedunculated lesions ≥20 mm removed by EMR. We assessed the discrimination and calibration of the GSEED-RE and ACER models. Difficulty performing EMR was subjectively categorized as low, medium, or high. We created a new model, including factors associated with DB in 3 cohort studies. RESULTS: DB occurred in 45 of 1034 EMRs (4.5%); it was associated with proximal location (odds ratio [OR], 2.84; 95% confidence interval [CI], 1.31-6.16), antiplatelet agents (OR, 2.51; 95% CI, .99-6.34) or anticoagulants (OR, 4.54; 95% CI, 2.14-9.63), difficulty of EMR (OR, 3.23; 95% CI, 1.41-7.40), and comorbidity (OR, 2.11; 95% CI, .99-4.47). The GSEED-RE and ACER models did not accurately predict DB. Re-estimation and recalibration yielded acceptable results (GSEED-RE area under the curve [AUC], .64 [95% CI, .54-.74]; ACER AUC, .65 [95% CI, .57-.73]). We used lesion size, proximal location, comorbidity, and antiplatelet or anticoagulant therapy to generate a new model, the GSEED-RE2, which achieved higher AUC values (.69-.73; 95% CI, .59-.80) and exhibited lower susceptibility to changes among datasets. CONCLUSIONS: The updated GSEED-RE and ACER models achieved acceptable prediction levels of DB. The GSEED-RE2 model may achieve better prediction results and could be used to guide the management of patients after validation by other external groups. (Clinical trial registration number: NCT03050333.).

Repeated ketamine administration induces recognition memory impairment together with morphological changes in neurons from ventromedial prefrontal cortex, dorsal striatum, and hippocampus.

Ketamine is an anesthetic agent that antagonizes N-methyl-d-aspartate receptors, inducing psychotic-like symptoms in healthy humans and animals. This agent has been used as a pharmacological tool for studying biochemical and physiological mechanisms underlying the clinical manifestations of schizophrenia. The main goal of this study was to evaluate the effect of repeated injections of ketamine (5 and 10 mg/kg, i.p., daily for 5 days) on recognition memory and neuronal morphology in ICR-CD1 mice. This treatment induced recognition memory impairment in the novel object recognition test and a decrease in dendritic spines density in both dorsal striatum and CA1-hippocampus. Sholl analysis showed that both ketamine doses decrease the dendritic arborization in ventromedial prefrontal cortex, dorsal striatum, and CA1-hippocampus. Finally, dendritic spines morphology was modified by both doses; that is, an increase of the filipodia-type spines (10 mg/kg) and a reduction of the mushroom-type spines (5 and 10 mg/kg) was observed in the ventromedial prefrontal cortex. In the dorsal striatum, the low dose of ketamine induced an increase in long thin spines and a decrease of mushroom spines. Interestingly, in CA1-hippocampus, there was an increase in the mushrooms type spines (5 mg/kg). Current findings suggest that the subchronic blockade of N-methyl-d-aspartate receptor changes the neuronal plasticity of several brain regions putatively related to recognition memory impairment.