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Es conocido que, cuando en el modelo de regresión lineal existe un alto grado de multicolinealidad, los resultados obtenidos a partir del método de mínimos cuadrados ordinarios (MCO) son inestables. Como solución a esta situación, en este trabajo se presentan los métodos de alzado, cresta y variables ortogonales como alternativa a la estimación por MCO. También se muestra que la regresión con variables ortogonales tiene sentido independientemente de la existencia de multicolinealidad grave, ya que permite dar respuesta a cuestiones no accesibles con el modelo original. Dichas metodologías se aplican a un conjunto de datos de rendimientos de letras del tesoro. || It is known that, when in the linear regression model there is a high degree of multicollinearity, the results obtained by using the Ordinary Least Squares (OLS) method are unstable. As a solution to this situation, in this paper we present the raised method, the ridge method and the orthogonal variables method as an alternative to the estimate by OLS. It is also shown that regression with orthogonal variables makes sense regardless of the existence of serious multicollinearity because it allows to answer questions which are not accessible when using the original model. These methodologies are applied to a data set of yields of treasury bills.

La mayoría de los trabajos publicados sobre la relación entre los factores institucionales y emprendedores adolecen de un adecuado estudio empírico. Debido a la importancia que ha adquirido en los últimos años el entorno institucional, consideramos necesario un análisis riguroso mediante técnicas estadísticas cuantitativas. El objetivo del presente trabajo es el análisis empírico de la relación entre el entorno institucional y la orientación emprendedora de la empresa española, partiendo de la identificación teórica y empírica de las dimensiones reguladora, cognitiva y normativa para el entorno institucional y las dimensiones de innovación, asunción de riesgos, proactividad y autonomía para analizar el comportamiento emprendedor. || The majority of published studies about the relation between institutional and entrepreneurial factors lack of an adequate empirical study. Due to the importance that the institutional environment has acquired in the last few years, we consider necessary a rigorous analysis using quantitative statistical techniques. The aim of this paper is the empirical analysis of the relation- ship between institutional and entrepreneurial orientation Spanish company, based on theoretical and empirical identification of regulatory, cognitive and normative dimensions for the institutional environment and the dimensions of innovation, risk assumption, proactivity, and autonomy to analyze the entrepreneurial behavior.

Abstract: Growing evidence indicates that 5-hydrohytryptamine (5-HT) receptors mediate learning and memory. Particularly interesting are 5-HT6 and 5-HT7 receptors, which are localized in brain areas involved in memory formation. Interestingly, recently selective 5-HT6 and 5-HT7 receptor agonists and antagonists have become available. Previous evidence indicates that 5-HT6 or 5-HT7 receptors antagonists had no effects, improved memory formation and/or reversed amnesia. Herein, the effects of EMD (a 5-HT6 receptor agonist) and AS19 (a 5-HT7 receptor agonist) in the associative learning task of autoshaping were studied. Post-training systemic administration of EMD (1–10mg/kg) or AS19 (1–10mg/kg) were tested in short-term memory (STM) and long-term memory (LTM). Results showed that only EMD 5.0mg/kg impaired both STM and LTM. AS19 at 1–10mg/kg significantly impaired STM but not LTM. In those groups used to test only LTM, EMD impaired it; while AS19 improved LTM. Moreover, in the interaction experiments, the STM EMD-impairment effect was partially reversed by the selective 5-HT6 receptor antagonist SB-399885 (10mg/kg). The STM AS19-impairment effect (5.0mg/kg) was not altered by the selective 5-HT1A antagonist WAY 100635 (0.3mg/kg) but reversed by the selective 5-HT7 receptor antagonist SB-269970 (10.0mg/kg). The AS19-SB-269970 combination impaired LTM. Taken together these data suggest that the stimulation of 5-HT6 impaired both STM and LTM. 5-HT7 receptors stimulation impaired STM but improved LTM. And these results are discussed in the context of their possible neural bases. [Copyright &y& Elsevier]

Purpose: To provide insights into the diagnosis and management of therapy-related myeloid neoplasms (t-MN) following PARP inhibitors (PARPi)., Experimental Design: In a French cancer center, we identified and described the profiles of 13 t-MN diagnosed among 37 patients with ovarian cancer referred to hematology consultation for cytopenia under PARPi. Next, we described these 13 t-MN post-PARPi among 37 t-MN post ovarian cancer according to PARPi exposure. Finally, we described 69 t-MN post-PARPi in a national cohort., Results: From 2016 to 2021, cumulative incidence of t-MN was 3.5% (13/373) among patients with ovarian cancer treated with PARPi. At time of hematologic consultation, patients with t-MN had a longer PARPi exposure (9 vs. 3 months, P = 0.01), lower platelet count (74 vs. 173 G/L, P = 0.0005), and more cytopenias (2 vs. 1, P = 0.0005). Compared with t-MN not exposed to PARPi, patients with t-MN-PARPi had more BRCA1/2 germline mutation (61.5% vs. 0%, P = 0.03) but similar overall survival (OS). In the national cohort, most t-MN post-PARPi had a complex karyotype (61%) associated with a high rate of TP53 mutation (71%). Median OS was 9.6 months (interquartile range, 4-14.6). In multivariate analysis, a longer time between end of PARPi and t-MN (HR, 1.046; P = 0.02), olaparib compared with other PARPi (HR, 5.82; P = 0.003) and acute myeloid leukemia (HR, 2.485; P = 0.01) were associated with shorter OS., Conclusions: In a large series, we described a high incidence of t-MN post-PARPi associated with unfavorable cytogenetic and molecular abnormalities leading to poor OS. Early detection is crucial, particularly in cases of delayed cytopenia., (©2022 American Association for Cancer Research.)

Background: Health beliefs are relevant to consider in patients with type 2 diabetes since disease control depends mainly on the patient's behaviour. The aim of this study was to assess the association between health beliefs and glycated hemoglobin levels in Mexican patients with type 2 diabetes., Methods: An analytical cross-sectional study was conducted, and 336 patients were included. Fasting blood levels of glycated hemoglobin, glucose, cholesterol; triglycerides, high-density lipoprotein cholesterol (HDL-c), and low-density lipoprotein cholesterol (LDL-c) were measured. Body fat percentage, weight, height; waist circumference, and systolic and diastolic blood pressures were also obtained. A previously validated self-administered questionnaire was used to assess the health beliefs with regards to non-pharmacological treatment. Health beliefs were classified as positive, neutral, and negative., Results: The average age of patients was 54.7 ± 8.5 years, with a higher proportion of females (69%). The questionnaire had a good internal consistency with a Cronbach's alpha score of 0.83. More than 90% of patients attributed a health benefit to diet and exercise, 30 to 40% experienced barriers, and more than 80% had a perception of complications associated to uncontrolled diabetes. Patients with positive health beliefs had lower HbA1c levels (8.2 ± 1.7%) compared to those with neutral (9.0 ± 2.3%), or negative (8.8 ± 1.8%; p = 0.042). The LDL-c levels were lower (p = 0.03), and HDL-c levels were higher (0.002) in patients with positive heath beliefs., Conclusions: Positive health beliefs are associated with better metabolic control indicators in patients with type 2 diabetes.

To our knowledge the intrahippocampal serotonergic 5-HT 6 receptor tone on memory and amnesia models remains unexplored. Hence, in the present work we tested intrahippocampal administration of serotonin or 5-hydroxytryptamine (5-HT) 6 receptor experimental molecules with differential intrinsic activity. Methods: In the present study, Automatized Autoshaping memory task was used, useful measuring memory, neural markers, and pharmacological effects. We are hypothesizing that experimental molecules with differential intrinsic activity might reveal serotonergic tone. Particularly, intrahippocampal administration of 5-HT 6 receptor compounds with differential intrinsic activity (i.e., agonistic and antagonistic) might evidencing a serotonergic tone via this receptor. Bilateral intrahippocampal dose-response curves show that administration of EMD386088 (10 and 100 μg) had no effect or (50 μg) decreased conditioned responses (CR) in short- and long-term memory (STM and LTM, respectively); while SB-399885 (10 or 100 μg) significantly decreased CR in STM and LTM (24 and 48-h) or (50 μg) had no effect; thus suggesting that there is a 5-HT 6 receptor tone regulating both STM and LTM. Moreover, intrahippocampal inactive doses of EMD386088 (5 μg) plus SB-399885 (0.5 μg) did not affect STM and LTM; however, partially or completely prevented the scopolamine or dizocilpine-induced amnesia. Thus confirming that both drugs exerted their effects through 5-HT 6 receptor and that there is a hippocampal serotonergic tone under amnesic states, similar to that striatal., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Autoimmune hemolytic anemia (AIHA) has been associated with chronic lymphocytic leukemia, non-Hodgkin lymphoma, and classical Hodgkin lymphoma, but to the best of our knowledge, the association of AIHA and nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) has not been reported previously. A 20-year-old woman presented with conjunctival jaundice, fever, asthenia, and hemoglobin 9.2 g/dL revealing IgG-mediated warm antibody AIHA. Computed tomography (CT) scan and positron-emission tomography (PET) scan showed mediastinal and axillary lymph nodes with increased [(18)F]-fluorodeoxyglucose uptake. A mediastinal lymph node was biopsied during mediastinoscopy, and NLPHL was diagnosed by an expert hematopathologist. The hemoglobin level declined to 4.6 g/dL. The treatment consisted of four 28-day cycles of R-ABVD (rituximab 375 mg/m(2) IV, adriamycin 25 mg/m(2) IV, bleomycin 10 mg/m(2) IV, vinblastine 6 mg/m(2) IV, and dacarbazine 375 mg/m(2) IV, each on days 1 and 15). Prednisone was progressively tapered over 10 weeks. After the first chemotherapy cycle, the hemoglobin level rose to 12 g/dL. After the four cycles, PET and CT scans showed complete remission (CR). At the last followup (4 years), AIHA and NLPHL were in sustained CR.

Notwithstanding several neurotransmission systems are frequently related to memory formation; forgetting process and neurotransmission systems or their transporters; the role of γ-aminobutyric acid (GAT1), glutamate (EACC1), dopamine (DAT) and serotonin (SERT) is poorly understood. Hence, in this paper western-blot analysis was used to evaluate expression of GAT1, EAAC1, DAT and SERT during forgetting in trained and untrained rats treated with the selective serotonin transporter inhibitor fluoxetine, the amnesic drug d-methamphetamine (METH) and fluoxetine plus METH. Transporters expression was determined in the hippocampus (HIP), prefrontal cortex (PFC) and striatum (STR). Results indicated that forgetting of Pavlovian/instrumental autoshaping was associated to up-regulation of GAT1 (PFC and HIP) and DAT (PFC) while SERT (HIP) was down-regulated; no-changes were observed in striatum. Methamphetamine administration did not affect forgetting at 216 h post-training but up-regulated hippocampal DAT and EACC, prefrontal cortex DAT and striatal GAT1 or EACC1. Fluoxetine alone prevented forgetting, which was associated to striatal GAT1 and hippocampal DAT up-regulation, but prefrontal cortex GAT1 down-regulation. Fluoxetine plus METH administration was also able to prevent forgetting, which was associated to hippocampal DAT, prefrontal cortex SERT and striatal GAT1, DAT or SERT up-regulation, but prefrontal cortex GAT1 down-regulation. Together these data show that forgetting provokes primarily hippocampal and prefrontal cortex transporters changes; forgetting represent a behavioral process hardly modifiable and its prevention could causes different transporters expression patterns., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Serotonin (5-hydroxytryptamien, 5-HT) has been linked to emotional and motivational aspects of human behavior, including anxiety, depression, impulsivity, etc. Several clinically effective drugs exert effects via 5-HT systems. Growing evidence suggests that those effects play an important role in learning and memory. Whether the role of serotonin is related to memory and/or behavioral or emotional aspects remains an important question. A key question that remains is whether 5-HT markers (e.g., receptors) directly or indirectly participate and/or contribute to the physiological and pharmacological basis of memory and its pathogenesis. The major aim of this paper is to re-examine some recent advances regarding mammalian 5-HT receptors and transporter in light of their physiological, pathophysiological and therapeutic implications for memory. We particularly address evidence involving 5-HT systems in behavioral, pharmacological, molecular, genetic and imaging results and memory. Finally, this paper aims to summarize a portion of the evidence about serotonin, memory and emotion from animal and human studies and provide an overview of potential tools, markers and cellular and molecular candidate mechanisms. It should be noted that there are several subjects that this paper only briefly touches upon, presenting only what may be the most salient findings in the context of memory, emotion and serotonin.

Intracerebroventricular (ICV) streptozotocin (STZ) treated rat has been described as a suitable model for sporadic Alzheimer's disease (AD). Central application of STZ has demonstrated behavioral and neurochemical features that resembled those found in human AD. Chronic treatments with antioxidants, acetylcholinesterase (AChE) inhibitors, or improving glucose utilization drugs have reported a beneficial effect in ICV STZ-treated rats. In the present study the post-training administration of a glycogen synthase kinase (GSK3) inhibitor, lithium; antidementia drugs: phenserine and memantine, and insulin sensitizer, pioglitazone on memory function of ICV STZ-rats was assessed. In these same animals the phosphorylated GSK3β (p-GSK3β) and total GSK3β levels were determined, and importantly GSK3β regulates the tau phosphorylation responsible for neurofibrillary tangle formation in AD. Wistar rats received ICV STZ application (3mg/kg twice) and 2 weeks later short- (STM) and long-term memories (LTM) were assessed in an autoshaping learning task. Animals were sacrificed immediately following the last autoshaping session, their brains removed and dissected. The enzymes were measured in the hippocampus and prefrontal cortex (PFC) by western blot. ICV STZ-treated rats showed a memory deficit and significantly decreased p-GSK3β levels, while total GSK3β did not change, in both the hippocampus and PFC. Memory impairment was reversed by lithium (100mg/kg), phenserine (1mg/kg), memantine (5mg/kg) and pioglitazone (30 mg/kg). The p-GSK3β levels were restored by lithium, phenserine and pioglitazone in the hippocampus, and restored by lithium in the PFC. Memantine produced no changes in p-GSK3β levels in neither the hippocampus nor PFC. Total GSK3β levels did not change with either drug. Altogether these results show the beneficial effects of drugs with different mechanisms of actions on memory impairment induced by ICV STZ, and restored p-GSK3β levels, a kinase key of signaling cascade of insulin receptor., (2011 Elsevier B.V. All rights reserved.)

This article describes a series of experiments investigating the effects of systemic or intraprefrontal administration of serotonergic agents on ketamine induced memory deficits in rats. First, rats were trained on an operant autoshaping task. Immediately after training, rats were injected with different doses of drug or saline. Following drug administration, rats were tested after 1.5 h for short-term memory (STM) and 24 h for long-term memory (LTM) of conditioned response. An increase or decrease in number of conditioned responses was an index of retention. The major results of this work show that ketamine impaired STM and this effect was reversed, by either systemic or intraprefrontal cortex administration of the agonist 5-HT(1A/7) 8-OH-DPAT, the 5-HT receptor antagonists MDL100907 (5-HT(2A)), SB-399885 (5-HT(6)), and SB-269970 (5-HT(7)). The ketamine STM-impairment effect was not altered by the 5-HT(1A) antagonist WAY 100635 or the 5-HT(1B) antagonist SB-224289. Notably, prefrontal cortex inhibition of translation or transcription interrupted STM without affecting LTM suggesting different signaling mechanisms. The interacting effect of NMDA and serotonin agents in memory function is an interesting and important area of study; both receptors are considered to be important targets for the development of antipsychotic medication. Particularly, 5-HT(1A/7), 5-HT(2A) 5-HT(6), and 5-HT(7) receptors present in prefrontal cortex, represent important targets for development of drugs for the treatment of SMT-deficits., ((c) 2008 Wiley-Liss, Inc.)

It was previously reported that brain areas containing serotonin (5-hydroxytryptamine, 5-HT) receptors mediate memory consolidation as well as short (STM)- and long-term memory (LTM). Here the effects of systemic and intrahippocampal administration of 5-HT agonists and antagonists on an autoshaping learning task were explored, which requires hippocampal translation and transduction as well as 5-HT receptors expression. As previously reported ketamine (glutamatergic antagonist) and two well-known amnesic drugs, scopolamine (cholinergic antagonist) and dizocilpine (NMDA antagonist) impaired STM but not LTM; dizocilpine even improved the latter. Since ketamine produces hallucinations and impairs memory in humans, we address the question if well-known antipsychotic haloperidol and clozapine might affect STM deficit. Indeed, systemic administration of clozapine

The effect of auranofin (AF) on in vitro correlates of human immune responsiveness was examined. AF inhibited mitogen induced human lymphocyte proliferation and the generation of immunoglobulin secreting cells in a concentration dependent manner. The inhibition was most effective when AF was present from the initiation of culture indicating that this drug blocked a critical early step in lymphocyte activation. Marked inhibition of mitogen responsiveness was observed as a result of a 1-h preincubation with AF. The brief preincubation with low concentrations of AF (0.3 micrograms/ml) resulted in a selective inhibition of the accessory function of monocytes but had no effect on potential lymphocyte responsiveness. Preincubation with higher concentrations of AF (greater than 0.6 micrograms/ml) resulted in a more non-specific inhibition of both monocyte and lymphocyte function. These data support the conclusion that AF may function as an immunosuppressive agent.