Mood disorders are often comorbid with alcohol use disorder (AUD) and play a considerable role in... more Mood disorders are often comorbid with alcohol use disorder (AUD) and play a considerable role in the development and maintenance of alcohol dependence and relapse. Because of this high comorbidity, it is necessary to determine shared and unique genetic factors driving heavy drinking and negative affective behaviors. In order to identify novel pharmacogenetic targets, a bioinformatics analysis was used to quantify the expression of amygdala K+ channel genes that covary with anxiety-related phenotypes in the well-phenotyped and fully sequenced family of BXD strains. We used a model of stress-induced escalation of drinking in alcohol-dependent mice to measure negative affective behaviors during abstinence. A pharmacological approach was used to validate the key bioinformatics findings in alcohol-dependent, stressed mice. Amygdalar expression of Kcnn3 correlated significantly with 40 anxiety-associated phenotypes. Further examination of Kcnn3 expression revealed a strong eigentrait for...
Anxiety and mood disorders are often comorbid with alcohol use disorder (AUD) and are considered ... more Anxiety and mood disorders are often comorbid with alcohol use disorder (AUD) and are considered critical in the development, maintenance, and reinstatement of alcohol dependence and harmful alcohol-seeking behaviors. Because of this high comorbidity, it is necessary to determine shared and unique genetic factors driving heavy ethanol drinking and anxiety-related behaviors. We used a model of stress-induced escalation of drinking in ethanol dependent C57BL/6J mice to measure anxiety-like behaviors on the marble burying and novelty-suppressed feeding task (NSFT) during abstinence. In order to identify novel pharmacogenetic targets that may lead to more effective treatment, a targeted bioinformatics analysis was used to quantify the expression of K+ channel genes in the amygdala that covary with anxiety-related phenotypes in the well phenotyped and fully sequenced family of BXD strains. A pharmacological approach was used to validate the key bioinformatics finding in ethanol-dependent...
Although previous research has demonstrated a role for kappa opioid receptor-mediated signaling i... more Although previous research has demonstrated a role for kappa opioid receptor-mediated signaling in escalated alcohol consumption associated with dependence and stress exposure, involvement of the dynorphin/kappa opioid receptor (DYN/KOR) system in binge-like drinking has not been fully explored. Here we used pharmacological and chemogenetic approaches to examine the influence of DYN/KOR signaling on alcohol consumption in the drinking-in-the-dark (DID) model of binge-like drinking. Systemic administration of the KOR agonist U50,488 increased binge-like drinking (Experiment 1) while, conversely, systemic administration of the KOR antagonist nor-BNI reduced drinking in the DID model (Experiment 2). These effects of systemic KOR manipulation were selective for alcohol as neither drug influenced consumption of sucrose in the DID paradigm (Experiment 3). In Experiment 4, administration of the long-acting KOR antagonist nor-BNI into the central nucleus of the amygdala (CeA) decreased alcohol intake. Next, targeted "silencing" of DYN+ neurons in the CeA was accomplished using a chemogenetic strategy. Cre-dependent viral expression in DYN+ neurons was confirmed in CeA of Pdyn-IRES-Cre mice and functionality of an inhibitory (hM4Di) DREADD was validated (Experiment 5). Activating the inhibitory DREADD by CNO injection reduced binge-like alcohol drinking, but CNO injection did not alter alcohol intake in mice that were treated with control virus (Experiment 6). Collectively, these results demonstrate that DYN/KOR signaling in the CeA contributes to excessive alcohol consumption in a binge-drinking model.
The BXD family of mice were generated by crossing and inbreeding ethanol-preferring C57BL/6J and ... more The BXD family of mice were generated by crossing and inbreeding ethanol-preferring C57BL/6J and ethanol-avoiding DBA/2J strains that differ greatly in genome sequence and other behaviors. This study evaluated variations in the level of voluntary ethanol intake in a cohort of 42 BXD strains and both progenitor strains using a model of alcohol dependence and relapse drinking. A total of 119 BXDs (85 males, 34 females) (n ∼ 4 per genotype; 1/genotype/sex/group) were evaluated along with males from both progenitor strains (n = 14-15/genotype). Mice were evaluated for intake using limited access (2 h/day) 2-bottle (15% v/v ethanol vs. water) model for 6 weeks (baseline intake). Each animal received 4 weekly cycles of chronic intermittent ethanol (CIE) vapor exposure (CIE group) or air control exposure (CTL group) (16 h/day × 4 days) interleaved by 5-day drinking test cycles. Blood ethanol concentrations (BEC) ranged from 150 to 300 mg/dl across genotypes. Baseline intake varied greatly ...
Chronic stress is a known contributing factor to the development of drug and alcohol addiction. A... more Chronic stress is a known contributing factor to the development of drug and alcohol addiction. Animal models have previously shown that repeated forced swim stress promotes escalated alcohol consumption in dependent animals. To investigate the underlying molecular adaptations associated with stress and chronic alcohol exposure, RNA-sequencing and bioinformatics analyses were conducted on the prefrontal cortex (CTX) of male C57BL/6J mice that were behaviorally tested for either non-dependent alcohol consumption (CTL), chronic intermittent ethanol (CIE) vapor dependent alcohol consumption, repeated bouts of forced swim stress alone (FSS), and chronic intermittent ethanol with forced swim stress (CIE + FSS). Brain tissue from each group was collected at 0-h, 72-h, and 168-h following the final test to determine long-lasting molecular changes associated with maladaptive behavior. Our results demonstrate unique temporal patterns and persistent changes in coordinately regulated gene expr...
N-Methyl-D-aspartate receptors (NMDARs) are glutamate-gated ion channels essential for glutamater... more N-Methyl-D-aspartate receptors (NMDARs) are glutamate-gated ion channels essential for glutamatergic transmission and plasticity. NMDARs are inhibited by acute ethanol and undergo brain region-specific adaptations after chronic alcohol exposure. In previous studies, we reported that knock-in mice expressing ethanol-insensitive GluN1 or GluN2A NMDAR subunits display altered behavioral responses to acute ethanol and genotype-dependent changes in drinking using protocols that do not produce dependence. A key unanswered question is whether the intrinsic ethanol sensitivity of NMDARs also plays a role in determining behavioral adaptations that accompany the development of dependence. To test this, we exposed mice to repeated cycles of chronic intermittent ethanol (CIE) vapor known to produce a robust escalation in ethanol consumption and preference. As expected, wild-type mice showed a significant increase from baseline in ethanol consumption and preference after each of the four weekly CIE cycles. In contrast, ethanol consumption in male GluN2A(A825W) mice was unchanged following cycles 1, 2, and 4 of CIE with a modest increase appearing after cycle 3. Wild-type and GluN2A(A825W) female mice did not show a clear or consistent escalation in ethanol consumption or preference following CIE treatment. In male GluN1(F639A) mice, the increase in ethanol consumption observed with their wild-type littermates was delayed until later cycles of exposure. These results suggest that the acute ethanol sensitivity of NMDARs especially those containing the GluN2A subunit may be a critical factor in the escalation of ethanol intake in alcohol dependence.
OBJECTIVES This analysis aimed to evaluate perioperative outcomes of surgical resection following... more OBJECTIVES This analysis aimed to evaluate perioperative outcomes of surgical resection following neoadjuvant treatment with chemotherapy plus nivolumab in resectable stage IIIA non-small-cell lung cancer. METHODS Eligible patients received neoadjuvant chemotherapy (paclitaxel + carboplatin) plus nivolumab for 3 cycles. Reassessment of the tumour was carried out after treatment and patients with at least stable disease as best response underwent pulmonary resection. After surgery, patients received adjuvant treatment with nivolumab for 1 year. Surgical data were collected from the NADIM database and patient charts were reviewed for additional surgical details. RESULTS Among 46 patients who received neoadjuvant treatment, 41 (89.1%) underwent surgery. Two patients rejected surgery and 3 did not fulfil resectability criteria. There were 35 lobectomies (85.3%), 3 of which were sleeve lobectomies (9.4%), 3 bilobectomies (7.3%) and 3 pneumonectomies (7.3%). Video-assisted thoracoscopy wa...
El artículo es un avance de un proyecto de investigación sobre extensión universitaria (EU): func... more El artículo es un avance de un proyecto de investigación sobre extensión universitaria (EU): función de la educación superior orientada al desarrollo social, cultural, productivo y medioambiental de los entornos universitarios. Pese a su relevancia la misma se desarrolla bastante pragmáticamente con poca orientación teórica por lo que estos estudios brindan elementos para la praxis extensionista. El objetivo del trabajo es mejorar la comprensión de la relación teoría-práctica en extensión universitaria en este caso delimitada al campo de la salud/salud pública. A partir del análisis de ponencias de congresos nacionales de extensión de Argentina, como caso testigo en la región, se examinan los resultados de cómo estos eventos están aportando a la construcción del objeto EU a partir de la red bibliográfica y el reagrupamiento de temas, objetos y sujetos. La metodología con la que se trabajó es la Grounded Theory.
This article presents the results of a research that aims to establish the perception of technolo... more This article presents the results of a research that aims to establish the perception of technological surveillance of undergraduate students at the Manizales Campus of the National University of Colombia. Technological surveillance, viewed as the permanent gathering of information about science and technology to convert it into knowledge, is not being well utilized by students. For the study, methods of observation, analysis and synthesis and a type of exploratory and correlational descriptive approach were used. The results show that the university is making significant efforts by the acquisition of technological tools and investing resources in mass media diffusion. However, students do not perceive these advances in an appropriate way and are not applying the available systems. For instance, the students are not massively using one of the most popular resources such as the mobile phones to make adequate technological surveillance. This study contributes to the academic community to define a baseline to future actions to enhance the use of technological surveillance tools in learning processes.
Small-conductance Ca 2+-activated K + (K Ca 2) channels control neuronal excitability and synapti... more Small-conductance Ca 2+-activated K + (K Ca 2) channels control neuronal excitability and synaptic plasticity, and have been implicated in substance abuse. However, it is unknown if genes that encode K Ca 2 channels (KCNN1-3) influence alcohol and drug addiction. In the present study, an integrative functional genomics approach shows that genetic datasets for alcohol, nicotine, and illicit drugs contain the family of KCNN genes. Alcohol preference and dependence QTLs contain KCNN2 and KCNN3, and Kcnn3 transcript levels in the nucleus accumbens (NAc) of genetically diverse BXD strains of mice predicted voluntary alcohol consumption. Transcript levels of Kcnn3 in the NAc negatively correlated with alcohol intake levels in BXD strains, and alcohol dependence enhanced the strength of this association. Microinjections of the K Ca 2 channel inhibitor apamin into the NAc increased alcohol intake in control C57BL/6J mice, while spontaneous seizures developed in alcohol-dependent mice following apamin injection. Consistent with this finding, alcohol dependence enhanced the intrinsic excitability of medium spiny neurons in the NAc core and reduced the function and protein expression of K Ca 2 channels in the NAc. Altogether, these data implicate the family of KCNN genes in alcohol, nicotine, and drug addiction, and identify KCNN3 as a mediator of voluntary and excessive alcohol consumption. K Ca 2.3 channels represent a promising novel target in the pharmacogenetic treatment of alcohol and drug addiction.
Objectives: The aims of this study were to design a best fit linear regression model to estimate ... more Objectives: The aims of this study were to design a best fit linear regression model to estimate VO 2max (estimated VO 2) and to compare the ability of VO 2 values (measured and estimated) predicting cardiorespiratory complications in a series of patients undergoing lung resection for lung cancer. Method: This was a prospective, observational study performed in 83 patients. Variables analyzed were: demographic characteristics, comorbidity, body mass index (BMI), FEV1%, FVC%, diffusion capacity (DLCO%), mean daily distance walked in kilometers, VO 2max measured by cardio-pulmonary exercise test (CPET) and postoperative complications. Descriptive and comparative statistical analysis of the variables was performed using the Mann-Whitney test for categorical variables and the Student's t-test for continuous variables. A new linear regression model was designed, where the dependent variable (measured VO 2max) was estimated by the distance, DLCO% and age, resulting in the estimated VO 2. The predictive power of the measured and estimated consumption was analyzed using the Student's t-test, grouping by the occurrence or absence of cardiorespiratory complications. Results: Both groups were homogeneous for age, sex, BMI, FEV1%, DLCO%, comorbidity, type of resection performed and mean distance walked per day. Estimated VO 2 and measured VO 2 were normally distributed (K-Smirnov test, P>.32). VO 2 means estimated by the model (age, DLCO% and mean distance walked per day) were significantly different between patients with and without complications (Student's t-test, P=.037) compared with measured VO 2 values, which did not differentiate groups (Student's t-test, P=.42). Conclusion: The VO 2max estimated by the model is more predictive in this case series than the VO 2max measured during a standard exercise test.
Volume 5: 13th Design for Manufacturability and the Lifecycle Conference; 5th Symposium on International Design and Design Education; 10th International Conference on Advanced Vehicle and Tire Technologies, 2008
This paper describes a multinational program aimed at teaching processes and methods for sustaina... more This paper describes a multinational program aimed at teaching processes and methods for sustainable product development using multidisciplinary project-based teams. The foundation course teaches processes for designing sustainable products and services, metrics and evaluation methods through a combination of lectures, project work, and examination of actual business cases. It is to be followed by courses on green manufacturing and pre-commercialization planning. The program features bi-national collaboration between the U.S. and Mexico, motivated by our shared vision for the development of sustainable solutions in a global context. The exploratory foundation course of the program, Design for Sustainability, was taught in Fall 2007 at the University of California at Berkeley with students and faculty members from 14 disciplines and three institutions: University of California at Berkeley (UCB), the California College of the Arts (CCA) in San Francisco, and the National University of...
Iran is au essmnal eltxuert for the normal functiou of many biological processes, including the i... more Iran is au essmnal eltxuert for the normal functiou of many biological processes, including the immune response and hematopoiiesis. Since iron dekiency results iu impaired cytokine prod&cm (TNF-a), weinvestigatedifircn,~dtoitstransportp~~transfeninorbyitself, modr&as the secretiar oftumor necrosis fictora ('pNF-a) by circxllating monocytes. In particular, we examined the effect of Tf-bound Iraq or ferric chloride (PeCl~) in the secr&iar of TNFa by cuhured blood mcmonuclear cells (BMNC) obtained from women with either normal Fe status (n=lO) or with ircn dekiency (n=lO). The add&r of 30 pM Tf, either in its apo or holo tbrm, to BMNC cultums derived from both normal and iron deficient subjects, induced a marked increase iu TNFa secretion by cells, to about 1.2-l .4 ngkuL. Sitnilarly, the addition of pM amounts of FeCla to normal BMNC resuhed in a dosr&pmdrnt increase of TNFu secretion. By contmst, BMNC fkom iron deticiett subjects were unable to secrete TNFu under similar ccmditions. Lipopolysaccharide (LPS) induced a maximal secretion of TNFu (3.9 f 0.6 ng/mL, mean f SEM) in BMNCderkdt?ombc&nomralandircnd&i~ women, an indicati~ that LB cells had the capacity to secrete TNFu in reqarseto a bacteriologic insult. However, the combinad addition of LPS and iron-salt did nd induce a further increase iu TNFu secretion. These fhrdings indicate that iron modula@ the in vitro secr&iar ofTNPu by human ma~au~clear cells through a process that depends both on the ircm status ofthe subject and ar the t&m in which Iran is supplied. Moreover, tmn&min also induces the secr&ion of TNFu in a way apparertly iudependea of its inmdaranng capacity.
Tactile stimulation of the neonate, as performed by the mother during and after delivery, has bee... more Tactile stimulation of the neonate, as performed by the mother during and after delivery, has been described as an effective unconditioned stimulus during early ontogeny (Leon, 1987; Ronca & Alberts, 1994). The present experiments examined the interaction between perinatal and neonatal learning determined by the explicit association between alcohol odor and vigorous body stimulation of the perinatal organism. In Experiment 1, rat fetuses were exposed to either alcohol or saline 10 min prior to cesarean delivery. The alcohol administration procedure here employed was sufficient to provide sensory contamination of the amniotic fluid but avoid fetal alcohol intoxication. Pups in the two prenatal treatments later experienced the smell of alcohol, tactile stimulation, or both stimuli explicitly paired or unpaired. Other postnatal groups were composed of pups that had no explicit experience with either experimental stimulus. Pups subjected to alcohol odor in utero displayed more overall motor activity in response to that odor than saline controls. The increased motor responses were further potentiated in pups that experienced additional postnatal alcohol odor paired with tactile stimulation. In Experiment 2, pups were exposed to alcohol in the amniotic fluid 10 or 30 min prior to birth. As previously demonstrated the memory acquired in utero appears highly dependent upon contingency between exposure to this particular scent and delivery procedures. Pups in both prenatal treatment groups were then exposed to alcohol odor paired or unpaired with tactile stimulation. Some control animals received no further experience with either stimuli. Those pups exposed to alcohol odor paired with tactile stimulation both pre-and postnatally later showed maximum motor activity elicited by the odor of alcohol. The results support the notion of fetal associative learning comprising alcohol's chemosensory cues and behaviorally activating stimuli. Furthermore, the conditioned response under analysis is potentiated whenever neonates are reexposed to contingent presentations of the elements that defined the original associative memory.
The Journal of Clinical Endocrinology & Metabolism, 2002
Circulating leptin levels, proinflammatory and T helper cells type 1 (Th1), Th2 cytokine producti... more Circulating leptin levels, proinflammatory and T helper cells type 1 (Th1), Th2 cytokine production, and lymphoproliferative response were measured in 15 infants with primary moderate protein calorie malnutrition on admission and after recovery of 10% of weight. Sixteen healthy, well nourished infants of comparable age served as controls. A significant deficit in the z-score of weight for age, weight for height, body mass index, and circulating leptin and growth factors were detected in malnourished infants on admission compared with controls (P < 0.05). These deficits were associated with a significant suppression of the lymphoproliferative response, Th1, and proinflammatory cytokine production (P < 0.05). After a 10% weight gain, a significant increase in circulating leptin levels was produced in parallel with a significant increase in Th1 activity, as revealed by an enhancement in interferon-␥ and a suppression in IL-4 production. Concomitantly, the lymphoproliferative response became similar to that detected in control infants. Furthermore, a significant increase in IL-1 and TNF␣ production compared with that at admission was shown. These findings suggest an association between the increase in leptin and the immunological recovery observed following refeeding of malnourished infants.
The latest tumour, lymph node and metastasis (TNM) classification by the International Associatio... more The latest tumour, lymph node and metastasis (TNM) classification by the International Association for the Study of Lung Cancer (IASLC), based on the analysis of patients from all over the world, has incorporated changes in the descriptors, especially those regarding tumor size, while proposing new group staging. A new lymph node map has also been developed with the intention of facilitating the classification of the &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot;N&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot; component. SEPAR recommends using this new classification. As for the procedures recommended for staging, in addition to the generalized use of computed tomography (CT), it points to the role of positron emission tomography (PET) or image fusion methods (PET/CT), which provide a better evaluation of the mediastinum and extrathoracic metastases. Endobronchial ultrasound (EBUS) and esophageal ultrasound (EUS) for obtaining cytohistological samples have been incorporated in the staging algorithm, and it emphasizes the importance of precise re-staging after induction treatment in order to make new therapeutic decisions. Comment is made on the foreseeable incorporation in the near future of molecular staging, and systematic lymph node dissection is recommended with the intention of making a more exact surgical-pathological classification.
Experience with stress situations during early development can have long-lasting effects on stres... more Experience with stress situations during early development can have long-lasting effects on stress and anxiety related behaviors. Importantly, this can also favor drug self-administration. These studies examined the effects of chronic social isolation and/or variable stress experiences during early development on subsequent voluntary ethanol intake in adult male and female C57BL/6J mice. The experiments were conducted to evaluate the effect of chronic isolation between weaning and adulthood (Experiment 1), chronic isolation during adulthood (Experiment 2) and chronic variable stress alone or in combination with chronic social isolation between weaning and adulthood (Experiment 3) on subsequent voluntary ethanol intake. Mice were born in our facility and were separated into two housing conditions: isolate-housed (1 mouse/cage) or group-housed (4 mice/cage), according to sex. Separate groups were isolated for 40 days starting either at time of weaning postnatal day 21 (PD 21) (early isolation, Experiments 1 and 3) or at adulthood (PD 60: late isolation, Experiment 2). The effects of housing condition on subsequent ethanol intake were assessed starting at around PD 65 in Experiments 1 and 3 or PD 105 days in Experiment 2. In Experiment 3, starting at PD 32, isolate-housed and group-housed mice were either subjected to chronic variable stress (CVS) or left undisturbed. CVS groups experienced random presentations of mild stressors for 14 days, including exposure to an unfamiliar open field, restraint, physical shaking, and forced swim, among others. All mice were tested for ethanol intake for 14 days using a 2-bottle choice (ethanol 15 % v/v vs. water) 2-hr limited access procedure. Early social isolation resulted in greater ethanol intake in comparison to the corresponding group-housed mice (Experiment 1). In contrast, social isolation during adulthood (late isolation) did not increase subsequent ethanol intake compared to the corresponding group-housed mice (Experiment 2). For mice that did not experience CVS, early social isolation resulted in greater ethanol intake compared to group-housed mice (Experiment 3). CVS subsequently resulted in a significant increase in ethanol intake in group-housed mice, but CVS failed to further increase ethanol intake in mice that experienced chronic social isolation early in life (Experiment 3). Overall, female mice consumed more ethanol than males, whether isolated (early or late) or group housed. These results indicate that early, but not late social isolation can subsequently influence ethanol consumption in C57BL/6J mice. Thus, the developmental timing of chronic social isolation appears to be an important factor in defining later effects on ethanol self-administration behavior. In addition,
Mood disorders are often comorbid with alcohol use disorder (AUD) and play a considerable role in... more Mood disorders are often comorbid with alcohol use disorder (AUD) and play a considerable role in the development and maintenance of alcohol dependence and relapse. Because of this high comorbidity, it is necessary to determine shared and unique genetic factors driving heavy drinking and negative affective behaviors. In order to identify novel pharmacogenetic targets, a bioinformatics analysis was used to quantify the expression of amygdala K+ channel genes that covary with anxiety-related phenotypes in the well-phenotyped and fully sequenced family of BXD strains. We used a model of stress-induced escalation of drinking in alcohol-dependent mice to measure negative affective behaviors during abstinence. A pharmacological approach was used to validate the key bioinformatics findings in alcohol-dependent, stressed mice. Amygdalar expression of Kcnn3 correlated significantly with 40 anxiety-associated phenotypes. Further examination of Kcnn3 expression revealed a strong eigentrait for...
Anxiety and mood disorders are often comorbid with alcohol use disorder (AUD) and are considered ... more Anxiety and mood disorders are often comorbid with alcohol use disorder (AUD) and are considered critical in the development, maintenance, and reinstatement of alcohol dependence and harmful alcohol-seeking behaviors. Because of this high comorbidity, it is necessary to determine shared and unique genetic factors driving heavy ethanol drinking and anxiety-related behaviors. We used a model of stress-induced escalation of drinking in ethanol dependent C57BL/6J mice to measure anxiety-like behaviors on the marble burying and novelty-suppressed feeding task (NSFT) during abstinence. In order to identify novel pharmacogenetic targets that may lead to more effective treatment, a targeted bioinformatics analysis was used to quantify the expression of K+ channel genes in the amygdala that covary with anxiety-related phenotypes in the well phenotyped and fully sequenced family of BXD strains. A pharmacological approach was used to validate the key bioinformatics finding in ethanol-dependent...
Although previous research has demonstrated a role for kappa opioid receptor-mediated signaling i... more Although previous research has demonstrated a role for kappa opioid receptor-mediated signaling in escalated alcohol consumption associated with dependence and stress exposure, involvement of the dynorphin/kappa opioid receptor (DYN/KOR) system in binge-like drinking has not been fully explored. Here we used pharmacological and chemogenetic approaches to examine the influence of DYN/KOR signaling on alcohol consumption in the drinking-in-the-dark (DID) model of binge-like drinking. Systemic administration of the KOR agonist U50,488 increased binge-like drinking (Experiment 1) while, conversely, systemic administration of the KOR antagonist nor-BNI reduced drinking in the DID model (Experiment 2). These effects of systemic KOR manipulation were selective for alcohol as neither drug influenced consumption of sucrose in the DID paradigm (Experiment 3). In Experiment 4, administration of the long-acting KOR antagonist nor-BNI into the central nucleus of the amygdala (CeA) decreased alcohol intake. Next, targeted "silencing" of DYN+ neurons in the CeA was accomplished using a chemogenetic strategy. Cre-dependent viral expression in DYN+ neurons was confirmed in CeA of Pdyn-IRES-Cre mice and functionality of an inhibitory (hM4Di) DREADD was validated (Experiment 5). Activating the inhibitory DREADD by CNO injection reduced binge-like alcohol drinking, but CNO injection did not alter alcohol intake in mice that were treated with control virus (Experiment 6). Collectively, these results demonstrate that DYN/KOR signaling in the CeA contributes to excessive alcohol consumption in a binge-drinking model.
The BXD family of mice were generated by crossing and inbreeding ethanol-preferring C57BL/6J and ... more The BXD family of mice were generated by crossing and inbreeding ethanol-preferring C57BL/6J and ethanol-avoiding DBA/2J strains that differ greatly in genome sequence and other behaviors. This study evaluated variations in the level of voluntary ethanol intake in a cohort of 42 BXD strains and both progenitor strains using a model of alcohol dependence and relapse drinking. A total of 119 BXDs (85 males, 34 females) (n ∼ 4 per genotype; 1/genotype/sex/group) were evaluated along with males from both progenitor strains (n = 14-15/genotype). Mice were evaluated for intake using limited access (2 h/day) 2-bottle (15% v/v ethanol vs. water) model for 6 weeks (baseline intake). Each animal received 4 weekly cycles of chronic intermittent ethanol (CIE) vapor exposure (CIE group) or air control exposure (CTL group) (16 h/day × 4 days) interleaved by 5-day drinking test cycles. Blood ethanol concentrations (BEC) ranged from 150 to 300 mg/dl across genotypes. Baseline intake varied greatly ...
Chronic stress is a known contributing factor to the development of drug and alcohol addiction. A... more Chronic stress is a known contributing factor to the development of drug and alcohol addiction. Animal models have previously shown that repeated forced swim stress promotes escalated alcohol consumption in dependent animals. To investigate the underlying molecular adaptations associated with stress and chronic alcohol exposure, RNA-sequencing and bioinformatics analyses were conducted on the prefrontal cortex (CTX) of male C57BL/6J mice that were behaviorally tested for either non-dependent alcohol consumption (CTL), chronic intermittent ethanol (CIE) vapor dependent alcohol consumption, repeated bouts of forced swim stress alone (FSS), and chronic intermittent ethanol with forced swim stress (CIE + FSS). Brain tissue from each group was collected at 0-h, 72-h, and 168-h following the final test to determine long-lasting molecular changes associated with maladaptive behavior. Our results demonstrate unique temporal patterns and persistent changes in coordinately regulated gene expr...
N-Methyl-D-aspartate receptors (NMDARs) are glutamate-gated ion channels essential for glutamater... more N-Methyl-D-aspartate receptors (NMDARs) are glutamate-gated ion channels essential for glutamatergic transmission and plasticity. NMDARs are inhibited by acute ethanol and undergo brain region-specific adaptations after chronic alcohol exposure. In previous studies, we reported that knock-in mice expressing ethanol-insensitive GluN1 or GluN2A NMDAR subunits display altered behavioral responses to acute ethanol and genotype-dependent changes in drinking using protocols that do not produce dependence. A key unanswered question is whether the intrinsic ethanol sensitivity of NMDARs also plays a role in determining behavioral adaptations that accompany the development of dependence. To test this, we exposed mice to repeated cycles of chronic intermittent ethanol (CIE) vapor known to produce a robust escalation in ethanol consumption and preference. As expected, wild-type mice showed a significant increase from baseline in ethanol consumption and preference after each of the four weekly CIE cycles. In contrast, ethanol consumption in male GluN2A(A825W) mice was unchanged following cycles 1, 2, and 4 of CIE with a modest increase appearing after cycle 3. Wild-type and GluN2A(A825W) female mice did not show a clear or consistent escalation in ethanol consumption or preference following CIE treatment. In male GluN1(F639A) mice, the increase in ethanol consumption observed with their wild-type littermates was delayed until later cycles of exposure. These results suggest that the acute ethanol sensitivity of NMDARs especially those containing the GluN2A subunit may be a critical factor in the escalation of ethanol intake in alcohol dependence.
OBJECTIVES This analysis aimed to evaluate perioperative outcomes of surgical resection following... more OBJECTIVES This analysis aimed to evaluate perioperative outcomes of surgical resection following neoadjuvant treatment with chemotherapy plus nivolumab in resectable stage IIIA non-small-cell lung cancer. METHODS Eligible patients received neoadjuvant chemotherapy (paclitaxel + carboplatin) plus nivolumab for 3 cycles. Reassessment of the tumour was carried out after treatment and patients with at least stable disease as best response underwent pulmonary resection. After surgery, patients received adjuvant treatment with nivolumab for 1 year. Surgical data were collected from the NADIM database and patient charts were reviewed for additional surgical details. RESULTS Among 46 patients who received neoadjuvant treatment, 41 (89.1%) underwent surgery. Two patients rejected surgery and 3 did not fulfil resectability criteria. There were 35 lobectomies (85.3%), 3 of which were sleeve lobectomies (9.4%), 3 bilobectomies (7.3%) and 3 pneumonectomies (7.3%). Video-assisted thoracoscopy wa...
El artículo es un avance de un proyecto de investigación sobre extensión universitaria (EU): func... more El artículo es un avance de un proyecto de investigación sobre extensión universitaria (EU): función de la educación superior orientada al desarrollo social, cultural, productivo y medioambiental de los entornos universitarios. Pese a su relevancia la misma se desarrolla bastante pragmáticamente con poca orientación teórica por lo que estos estudios brindan elementos para la praxis extensionista. El objetivo del trabajo es mejorar la comprensión de la relación teoría-práctica en extensión universitaria en este caso delimitada al campo de la salud/salud pública. A partir del análisis de ponencias de congresos nacionales de extensión de Argentina, como caso testigo en la región, se examinan los resultados de cómo estos eventos están aportando a la construcción del objeto EU a partir de la red bibliográfica y el reagrupamiento de temas, objetos y sujetos. La metodología con la que se trabajó es la Grounded Theory.
This article presents the results of a research that aims to establish the perception of technolo... more This article presents the results of a research that aims to establish the perception of technological surveillance of undergraduate students at the Manizales Campus of the National University of Colombia. Technological surveillance, viewed as the permanent gathering of information about science and technology to convert it into knowledge, is not being well utilized by students. For the study, methods of observation, analysis and synthesis and a type of exploratory and correlational descriptive approach were used. The results show that the university is making significant efforts by the acquisition of technological tools and investing resources in mass media diffusion. However, students do not perceive these advances in an appropriate way and are not applying the available systems. For instance, the students are not massively using one of the most popular resources such as the mobile phones to make adequate technological surveillance. This study contributes to the academic community to define a baseline to future actions to enhance the use of technological surveillance tools in learning processes.
Small-conductance Ca 2+-activated K + (K Ca 2) channels control neuronal excitability and synapti... more Small-conductance Ca 2+-activated K + (K Ca 2) channels control neuronal excitability and synaptic plasticity, and have been implicated in substance abuse. However, it is unknown if genes that encode K Ca 2 channels (KCNN1-3) influence alcohol and drug addiction. In the present study, an integrative functional genomics approach shows that genetic datasets for alcohol, nicotine, and illicit drugs contain the family of KCNN genes. Alcohol preference and dependence QTLs contain KCNN2 and KCNN3, and Kcnn3 transcript levels in the nucleus accumbens (NAc) of genetically diverse BXD strains of mice predicted voluntary alcohol consumption. Transcript levels of Kcnn3 in the NAc negatively correlated with alcohol intake levels in BXD strains, and alcohol dependence enhanced the strength of this association. Microinjections of the K Ca 2 channel inhibitor apamin into the NAc increased alcohol intake in control C57BL/6J mice, while spontaneous seizures developed in alcohol-dependent mice following apamin injection. Consistent with this finding, alcohol dependence enhanced the intrinsic excitability of medium spiny neurons in the NAc core and reduced the function and protein expression of K Ca 2 channels in the NAc. Altogether, these data implicate the family of KCNN genes in alcohol, nicotine, and drug addiction, and identify KCNN3 as a mediator of voluntary and excessive alcohol consumption. K Ca 2.3 channels represent a promising novel target in the pharmacogenetic treatment of alcohol and drug addiction.
Objectives: The aims of this study were to design a best fit linear regression model to estimate ... more Objectives: The aims of this study were to design a best fit linear regression model to estimate VO 2max (estimated VO 2) and to compare the ability of VO 2 values (measured and estimated) predicting cardiorespiratory complications in a series of patients undergoing lung resection for lung cancer. Method: This was a prospective, observational study performed in 83 patients. Variables analyzed were: demographic characteristics, comorbidity, body mass index (BMI), FEV1%, FVC%, diffusion capacity (DLCO%), mean daily distance walked in kilometers, VO 2max measured by cardio-pulmonary exercise test (CPET) and postoperative complications. Descriptive and comparative statistical analysis of the variables was performed using the Mann-Whitney test for categorical variables and the Student's t-test for continuous variables. A new linear regression model was designed, where the dependent variable (measured VO 2max) was estimated by the distance, DLCO% and age, resulting in the estimated VO 2. The predictive power of the measured and estimated consumption was analyzed using the Student's t-test, grouping by the occurrence or absence of cardiorespiratory complications. Results: Both groups were homogeneous for age, sex, BMI, FEV1%, DLCO%, comorbidity, type of resection performed and mean distance walked per day. Estimated VO 2 and measured VO 2 were normally distributed (K-Smirnov test, P>.32). VO 2 means estimated by the model (age, DLCO% and mean distance walked per day) were significantly different between patients with and without complications (Student's t-test, P=.037) compared with measured VO 2 values, which did not differentiate groups (Student's t-test, P=.42). Conclusion: The VO 2max estimated by the model is more predictive in this case series than the VO 2max measured during a standard exercise test.
Volume 5: 13th Design for Manufacturability and the Lifecycle Conference; 5th Symposium on International Design and Design Education; 10th International Conference on Advanced Vehicle and Tire Technologies, 2008
This paper describes a multinational program aimed at teaching processes and methods for sustaina... more This paper describes a multinational program aimed at teaching processes and methods for sustainable product development using multidisciplinary project-based teams. The foundation course teaches processes for designing sustainable products and services, metrics and evaluation methods through a combination of lectures, project work, and examination of actual business cases. It is to be followed by courses on green manufacturing and pre-commercialization planning. The program features bi-national collaboration between the U.S. and Mexico, motivated by our shared vision for the development of sustainable solutions in a global context. The exploratory foundation course of the program, Design for Sustainability, was taught in Fall 2007 at the University of California at Berkeley with students and faculty members from 14 disciplines and three institutions: University of California at Berkeley (UCB), the California College of the Arts (CCA) in San Francisco, and the National University of...
Iran is au essmnal eltxuert for the normal functiou of many biological processes, including the i... more Iran is au essmnal eltxuert for the normal functiou of many biological processes, including the immune response and hematopoiiesis. Since iron dekiency results iu impaired cytokine prod&cm (TNF-a), weinvestigatedifircn,~dtoitstransportp~~transfeninorbyitself, modr&as the secretiar oftumor necrosis fictora ('pNF-a) by circxllating monocytes. In particular, we examined the effect of Tf-bound Iraq or ferric chloride (PeCl~) in the secr&iar of TNFa by cuhured blood mcmonuclear cells (BMNC) obtained from women with either normal Fe status (n=lO) or with ircn dekiency (n=lO). The add&r of 30 pM Tf, either in its apo or holo tbrm, to BMNC cultums derived from both normal and iron deficient subjects, induced a marked increase iu TNFa secretion by cells, to about 1.2-l .4 ngkuL. Sitnilarly, the addition of pM amounts of FeCla to normal BMNC resuhed in a dosr&pmdrnt increase of TNFu secretion. By contmst, BMNC fkom iron deticiett subjects were unable to secrete TNFu under similar ccmditions. Lipopolysaccharide (LPS) induced a maximal secretion of TNFu (3.9 f 0.6 ng/mL, mean f SEM) in BMNCderkdt?ombc&nomralandircnd&i~ women, an indicati~ that LB cells had the capacity to secrete TNFu in reqarseto a bacteriologic insult. However, the combinad addition of LPS and iron-salt did nd induce a further increase iu TNFu secretion. These fhrdings indicate that iron modula@ the in vitro secr&iar ofTNPu by human ma~au~clear cells through a process that depends both on the ircm status ofthe subject and ar the t&m in which Iran is supplied. Moreover, tmn&min also induces the secr&ion of TNFu in a way apparertly iudependea of its inmdaranng capacity.
Tactile stimulation of the neonate, as performed by the mother during and after delivery, has bee... more Tactile stimulation of the neonate, as performed by the mother during and after delivery, has been described as an effective unconditioned stimulus during early ontogeny (Leon, 1987; Ronca & Alberts, 1994). The present experiments examined the interaction between perinatal and neonatal learning determined by the explicit association between alcohol odor and vigorous body stimulation of the perinatal organism. In Experiment 1, rat fetuses were exposed to either alcohol or saline 10 min prior to cesarean delivery. The alcohol administration procedure here employed was sufficient to provide sensory contamination of the amniotic fluid but avoid fetal alcohol intoxication. Pups in the two prenatal treatments later experienced the smell of alcohol, tactile stimulation, or both stimuli explicitly paired or unpaired. Other postnatal groups were composed of pups that had no explicit experience with either experimental stimulus. Pups subjected to alcohol odor in utero displayed more overall motor activity in response to that odor than saline controls. The increased motor responses were further potentiated in pups that experienced additional postnatal alcohol odor paired with tactile stimulation. In Experiment 2, pups were exposed to alcohol in the amniotic fluid 10 or 30 min prior to birth. As previously demonstrated the memory acquired in utero appears highly dependent upon contingency between exposure to this particular scent and delivery procedures. Pups in both prenatal treatment groups were then exposed to alcohol odor paired or unpaired with tactile stimulation. Some control animals received no further experience with either stimuli. Those pups exposed to alcohol odor paired with tactile stimulation both pre-and postnatally later showed maximum motor activity elicited by the odor of alcohol. The results support the notion of fetal associative learning comprising alcohol's chemosensory cues and behaviorally activating stimuli. Furthermore, the conditioned response under analysis is potentiated whenever neonates are reexposed to contingent presentations of the elements that defined the original associative memory.
The Journal of Clinical Endocrinology & Metabolism, 2002
Circulating leptin levels, proinflammatory and T helper cells type 1 (Th1), Th2 cytokine producti... more Circulating leptin levels, proinflammatory and T helper cells type 1 (Th1), Th2 cytokine production, and lymphoproliferative response were measured in 15 infants with primary moderate protein calorie malnutrition on admission and after recovery of 10% of weight. Sixteen healthy, well nourished infants of comparable age served as controls. A significant deficit in the z-score of weight for age, weight for height, body mass index, and circulating leptin and growth factors were detected in malnourished infants on admission compared with controls (P < 0.05). These deficits were associated with a significant suppression of the lymphoproliferative response, Th1, and proinflammatory cytokine production (P < 0.05). After a 10% weight gain, a significant increase in circulating leptin levels was produced in parallel with a significant increase in Th1 activity, as revealed by an enhancement in interferon-␥ and a suppression in IL-4 production. Concomitantly, the lymphoproliferative response became similar to that detected in control infants. Furthermore, a significant increase in IL-1 and TNF␣ production compared with that at admission was shown. These findings suggest an association between the increase in leptin and the immunological recovery observed following refeeding of malnourished infants.
The latest tumour, lymph node and metastasis (TNM) classification by the International Associatio... more The latest tumour, lymph node and metastasis (TNM) classification by the International Association for the Study of Lung Cancer (IASLC), based on the analysis of patients from all over the world, has incorporated changes in the descriptors, especially those regarding tumor size, while proposing new group staging. A new lymph node map has also been developed with the intention of facilitating the classification of the &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot;N&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot; component. SEPAR recommends using this new classification. As for the procedures recommended for staging, in addition to the generalized use of computed tomography (CT), it points to the role of positron emission tomography (PET) or image fusion methods (PET/CT), which provide a better evaluation of the mediastinum and extrathoracic metastases. Endobronchial ultrasound (EBUS) and esophageal ultrasound (EUS) for obtaining cytohistological samples have been incorporated in the staging algorithm, and it emphasizes the importance of precise re-staging after induction treatment in order to make new therapeutic decisions. Comment is made on the foreseeable incorporation in the near future of molecular staging, and systematic lymph node dissection is recommended with the intention of making a more exact surgical-pathological classification.
Experience with stress situations during early development can have long-lasting effects on stres... more Experience with stress situations during early development can have long-lasting effects on stress and anxiety related behaviors. Importantly, this can also favor drug self-administration. These studies examined the effects of chronic social isolation and/or variable stress experiences during early development on subsequent voluntary ethanol intake in adult male and female C57BL/6J mice. The experiments were conducted to evaluate the effect of chronic isolation between weaning and adulthood (Experiment 1), chronic isolation during adulthood (Experiment 2) and chronic variable stress alone or in combination with chronic social isolation between weaning and adulthood (Experiment 3) on subsequent voluntary ethanol intake. Mice were born in our facility and were separated into two housing conditions: isolate-housed (1 mouse/cage) or group-housed (4 mice/cage), according to sex. Separate groups were isolated for 40 days starting either at time of weaning postnatal day 21 (PD 21) (early isolation, Experiments 1 and 3) or at adulthood (PD 60: late isolation, Experiment 2). The effects of housing condition on subsequent ethanol intake were assessed starting at around PD 65 in Experiments 1 and 3 or PD 105 days in Experiment 2. In Experiment 3, starting at PD 32, isolate-housed and group-housed mice were either subjected to chronic variable stress (CVS) or left undisturbed. CVS groups experienced random presentations of mild stressors for 14 days, including exposure to an unfamiliar open field, restraint, physical shaking, and forced swim, among others. All mice were tested for ethanol intake for 14 days using a 2-bottle choice (ethanol 15 % v/v vs. water) 2-hr limited access procedure. Early social isolation resulted in greater ethanol intake in comparison to the corresponding group-housed mice (Experiment 1). In contrast, social isolation during adulthood (late isolation) did not increase subsequent ethanol intake compared to the corresponding group-housed mice (Experiment 2). For mice that did not experience CVS, early social isolation resulted in greater ethanol intake compared to group-housed mice (Experiment 3). CVS subsequently resulted in a significant increase in ethanol intake in group-housed mice, but CVS failed to further increase ethanol intake in mice that experienced chronic social isolation early in life (Experiment 3). Overall, female mice consumed more ethanol than males, whether isolated (early or late) or group housed. These results indicate that early, but not late social isolation can subsequently influence ethanol consumption in C57BL/6J mice. Thus, the developmental timing of chronic social isolation appears to be an important factor in defining later effects on ethanol self-administration behavior. In addition,
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Papers by Marcelo Lopez