Effect of vitamin E and memantine on functional decline in Alzheimer disease: the TEAM-AD VA cooperative randomized trial.

IMPORTANCE: Although vitamin E and memantine have been shown to have beneficial effects in moderately severe Alzheimer disease (AD), evidence is limited in mild to moderate AD. OBJECTIVE: To determine if vitamin E (alpha tocopherol), memantine, or both slow progression of mild to moderate AD in patients taking an acetylcholinesterase inhibitor. DESIGN, SETTING, AND PARTICIPANTS: Double-blind, placebo-controlled, parallel-group, randomized clinical trial involving 613 patients with mild to moderate AD initiated in August 2007 and concluded in September 2012 at 14 Veterans Affairs medical centers. INTERVENTIONS: Participants received either 2000 IU/d of alpha tocopherol (n = 152), 20 mg/d of memantine (n = 155), the combination (n = 154), or placebo (n = 152). MAIN OUTCOMES AND MEASURES: Alzheimer's Disease Cooperative Study/Activities of Daily Living (ADCS-ADL) Inventory score (range, 0-78). Secondary outcomes included cognitive, neuropsychiatric, functional, and caregiver measures. RESULTS: Data from 561 participants were analyzed (alpha tocopherol = 140, memantine = 142, combination = 139, placebo = 140), with 52 excluded because of a lack of any follow-up data. Over the mean (SD) follow-up of 2.27 (1.22) years, ADCS-ADL Inventory scores declined by 3.15 units (95% CI, 0.92 to 5.39; adjusted P = .03) less in the alpha tocopherol group compared with the placebo group. In the memantine group, these scores declined 1.98 units less (95% CI, -0.24 to 4.20; adjusted P = .40) than the placebo group's decline. This change in the alpha tocopherol group translates into a delay in clinical progression of 19% per year compared with placebo or a delay of approximately 6.2 months over the follow-up period. Caregiver time increased least in the alpha tocopherol group. All-cause mortality and safety analyses showed a difference only on the serious adverse event of "infections or infestations," with greater frequencies in the memantine (31 events in 23 participants) and combination groups (44 events in 31 participants) compared with placebo (13 events in 11 participants). CONCLUSIONS AND RELEVANCE: Among patients with mild to moderate AD, 2000 IU/d of alpha tocopherol compared with placebo resulted in slower functional decline. There were no significant differences in the groups receiving memantine alone or memantine plus alpha tocopherol. These findings suggest benefit of alpha tocopherol in mild to moderate AD by slowing functional decline and decreasing caregiver burden. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00235716.

Vitamin E and memantine in Alzheimer's disease: clinical trial methods and baseline data.

BACKGROUND: Alzheimer's disease (AD) has been associated with both oxidative stress and excessive glutamate activity. A clinical trial was designed to compare the effectiveness of (i) alpha-tocopherol, a vitamin E antioxidant; (ii) memantine (Namenda), an N-methyl-D-aspartate antagonist; (iii) their combination; and (iv) placebo in delaying clinical progression in AD. METHODS: The Veterans Affairs Cooperative Studies Program initiated a multicenter, randomized, double-blind, placebo-controlled trial in August 2007, with enrollment through March 2012 and follow-up continuing through September 2012. Participants with mild-to-moderate AD who were taking an acetylcholinesterase inhibitor were assigned randomly to 2000 IU/day of alpha-tocopherol, 20 mg/day memantine, 2000 IU/day alpha-tocopherol plus 20 mg/day memantine, or placebo. The primary outcome for the study is the Alzheimer's Disease Cooperative Study/Activities of Daily Living Inventory. Secondary outcome measures include the Mini-Mental State Examination; the Alzheimer's Disease Assessment Scale, cognitive portion; the Dependence Scale; the Neuropsychiatric Inventory; and the Caregiver Activity Survey. Patient follow-up ranged from 6 months to 4 years. RESULTS: A total of 613 participants were randomized. The majority of the patients were male (97%) and white (86%), with a mean age of 79 years. The mean Alzheimer's Disease Cooperative Study/Activities of Daily Living Inventory score at entry was 57 and the mean Mini-Mental State Examination score at entry was 21. CONCLUSION: This large multicenter trial will address the unanswered question of the long-term safety and effectiveness of alpha-tocopherol, memantine, and their combination in patients with mild-to-moderate AD taking an acetylcholinesterase inhibitor. The results are expected in early 2013.

Personality Unleashed: Surveying Correlation of Neuter Status and Social Behaviour in Mixed-Breed Male Dogs across Weight Classes.

This study investigates the behavioural differences between neutered and intact dogs. A total of 230 questionnaires of neutered (n = 115) and intact (n = 115) mixed-breed male dogs were collected. Small, medium, large, and giant dogs were analysed to investigate a possible influence of body size. The results showed neuters were significantly more stressed than intacts (multinomial logistic regression, p = 0.001). In terms of stress by influences (such as separation anxiety and anxiety at car rides), neutered small, medium, and large dogs were more stressed than giant dogs (multinomial logistic regression, p = 0.05). Neuters were also found to be more aggressive in general (multinomial logistic regression, p = 0.04) and more aggressive on the walk (multinomial logistic regression, p = 0.02). In addition, personality questionnaires revealed significant differences in all characteristics. Neuters were less emotionally calm (multiple ordinal regression, p = 0.03), less trainable and less sociable (each multiple ordinal regression, p < 0.001). They also scored lower on extraversion (multiple ordinal regression, p = 0.04). These findings highlight the importance of further research into the behavioural effects of neutering dogs, as well as the need for evidence-based guidelines for neutering practices.

Soluble M6P/IGF2R released by TACE controls angiogenesis via blocking plasminogen activation.

RATIONALE: The urokinase plasminogen activator (uPA) system is among the most crucial pericellular proteolytic systems associated with the processes of angiogenesis. We previously identified an important regulator of the uPA system in the mannose 6-phosphate/insulin-like growth factor 2 receptor (M6P/IGF2R). OBJECTIVE: Here, we wanted to clarify whether and how did the soluble form of M6P/IGF2R (sM6P/IGF2R) contribute to modulation of the uPA system. METHODS AND RESULTS: By using specific inhibitors and RNA interference, we show that the tumor necrosis factor α convertase (TACE, ADAM-17) mediates the release of the ectodomain of M6P/IGF2R from human endothelial cells. We demonstrate further that sM6P/IGF2R binds plasminogen (Plg) and thereby prevents Plg from binding to the cell surface and uPA, ultimately inhibiting in this manner Plg activation. Furthermore, peptide 18-36 derived from the Plg-binding site of M6P/IGF2R mimics sM6P/IGF2R in the inhibition of Plg activation and blocks cancer cell invasion in vitro, endothelial cell invasion in vivo, and tumor growth in vivo. CONCLUSIONS: The interaction of sM6P/IGF2R with Plg may be an important regulatory mechanism to inhibit migration of cells using the uPA/uPAR system.

CD28 costimulatory signal induces protein arginine methylation in T cells.

Protein phosphorylation initiates signal transduction that triggers lymphocyte activation. However, other posttranslational modifications may contribute to this process. Here, we show that CD28 engagement induced protein arginine methyltransferase activity and methylation on arginine of several proteins, including Vav1. Methylation of Vav1 and IL-2 production were reduced by inhibiting S-adenosyl-L-homocysteine hydrolase, an enzyme that regulates cellular transmethylation. Methylated Vav1 was induced in human and mouse T cells and selectively localized in the nucleus, which suggested that this form marks a nuclear function of Vav1. Our findings uncover a signaling pathway that is controlled by CD28 that is likely to be important for T cell activation.

DYRK1A interacts with the REST/NRSF-SWI/SNF chromatin remodelling complex to deregulate gene clusters involved in the neuronal phenotypic traits of Down syndrome.

The molecular mechanisms that lead to the cognitive defects characteristic of Down syndrome (DS), the most frequent cause of mental retardation, have remained elusive. Here we use a transgenic DS mouse model (152F7 line) to show that DYRK1A gene dosage imbalance deregulates chromosomal clusters of genes located near neuron-restrictive silencer factor (REST/NRSF) binding sites. We found that Dyrk1a binds the SWI/SNF complex known to interact with REST/NRSF. The mutation of a REST/NRSF binding site in the promoter of the REST/NRSF target gene L1cam modifies the transcriptional effect of Dyrk1a-dosage imbalance on L1cam. Dyrk1a dosage imbalance perturbs Rest/Nrsf levels with decreased Rest/Nrsf expression in embryonic neurons and increased expression in adult neurons. Using transcriptome analysis of embryonic brain subregions of transgenic 152F7 mouse line, we identified a coordinated deregulation of multiple genes that are responsible for dendritic growth impairment present in DS. Similarly, Dyrk1a overexpression in primary mouse cortical neurons induced severe reduction of the dendritic growth and dendritic complexity. We propose that DYRK1A overexpression-related neuronal gene deregulation via disturbance of REST/NRSF levels, and the REST/NRSF-SWI/SNF chromatin remodelling complex, significantly contributes to the neural phenotypic changes that characterize DS.

Coxsackie B3 Virus-induced Acute Hemorrhagic Edema of Infancy.

Acute hemorrhagic edema of infancy (AHEI) is a cutaneous leukocytoclastic small vessel vasculitis of unknown incidence. It affects mostly infants aged 4 to 24 months. The distinctive features of AHEI include a generally healthy-appearing child with low-grade or absent fever and rarely painful targetoid purpuric edematous lesions. The disease usually resolves spontaneously within 3 weeks without late sequelae. The main differential diagnosis of AHEI is Henoch-Schönlein purpura (HSP). Initially, purpura fulminans should also be ruled out. We report the case of a 5-year-old girl with low fever and rapidly progressive skin lesions who had been admitted to the pediatric clinic. The child presented with palpable annular targetoid and purpuric plaques of different size predominantly affecting the face and extremities. In addition, there was a painful, hemorrhagic edema on the dorsum of her hands and feet. Based on the course of the disease and the typical clinical presentation, i.e., extensive characteristic skin lesions in a young child in a good general health condition, a diagnosis of AHEI was established. A virus serology test showed increased titers of enterovirus and coxsackievirus. Isolation of virus from feces confirmed an infection with coxsackie B3 virus. To our knowledge, this is the first report linking coxsackie B3 virus infection to AHEI.

Helicobacter pylori exploits cholesterol-rich microdomains for induction of NF-kappaB-dependent responses and peptidoglycan delivery in epithelial cells.

Infection with Helicobacter pylori cag pathogenicity island (cagPAI)-positive strains is associated with more destructive tissue damage and an increased risk of severe disease. The cagPAI encodes a type IV secretion system (TFSS) that delivers the bacterial effector molecules CagA and peptidoglycan into the host cell cytoplasm, thereby inducing responses in host cells. It was previously shown that interactions between CagL, present on the TFSS pilus, and host α(5)ß(1) integrin molecules were critical for CagA translocation and the induction of cytoskeletal rearrangements in epithelial cells. As the α(5)ß(1) integrin is found in cholesterol-rich microdomains (known as lipid rafts), we hypothesized that these domains may also be involved in the induction of proinflammatory responses mediated by NOD1 recognition of H. pylori peptidoglycan. Indeed, not only did methyl-ß-cyclodextrin depletion of cholesterol from cultured epithelial cells have a significant effect on the levels of NF-κB and interleukin-8 (IL-8) responses induced by H. pylori bacteria with an intact TFSS (P < 0.05), but it also interfered with TFSS-mediated peptidoglycan delivery to cells. Both of these effects could be restored by cholesterol replenishment of the cells. Furthermore, we demonstrated for the first time the involvement of α(5)ß(1) integrin in the induction of proinflammatory responses by H. pylori. Taking the results together, we propose that α(5)ß(1) integrin, which is associated with cholesterol-rich microdomains at the host cell surface, is required for NOD1 recognition of peptidoglycan and subsequent induction of NF-κB-dependent responses to H. pylori. These data implicate cholesterol-rich microdomains as a novel platform for TFSS-dependent delivery of bacterial products to cytosolic pathogen recognition molecules.

Implementing the Clean Clinic Approach Improves Water, Sanitation, and Hygiene Quality in Health Facilities in the Western Highlands of Guatemala.

BACKGROUND: Water, sanitation, and hygiene (WASH) services are cornerstones to providing safe health care services and improving patient satisfaction and care seeking. The Clean Clinic Approach (CCA) uses a 10-step process to support health care facilities (HCFs) in making incremental, effective cleanliness and infection prevention and control (IPC) improvements, without relying on external investments. We piloted the CCA in Guatemala and assessed the extent to which it contributed to quality improvements in WASH for IPC. METHODS: After developing an assessment tool tailored to the Guatemalan context, we assessed 11 HCFs in 8 technical areas and scored the facilities on 79 criteria with a total of 100 points. We conducted a baseline assessment (September to October 2018), second assessment (January 2019), and final assessment (February to March 2019). RESULTS: The 11 HCFs improved their average emergency/general ward scores from 41 points at baseline to 87 points at end line, based on a 100-point scale. For delivery wards, the scores increased from 50 to 91 points and for postnatal wards from 46 to 90 points. CONCLUSIONS: The CCA process and tools facilitated a systematic way for HCFs to identify, prioritize, make, and measure WASH quality of care improvements. Training facility staff was fundamental to improving quality standards, and involving medical and administration staff in joint analysis, coordination, and planning sessions was key to integration and teamwork. Further work is needed to increase involvement of local government and community members and to further adapt the process and tools.

Isatin binding proteins in rat brain: in situ imaging, quantitative characterization of specific [3H]isatin binding, and proteomic profiling.

Isatin (indole-2,3-dione) is an endogenous indole that has a distinct and discontinuous distribution in the brain and in other mammalian tissues and body fluids. Its output is increased under conditions of stress and anxiety. Its biological targets remain poorly characterized, although [(3)H]isatin binding sites have been demonstrated in various brain structures. In this study, by using a real-time beta-imager, [(3)H]isatin radioligand binding analysis, and proteomic identification of proteins specifically bound to the affinity sorbent 5-aminocaproyl-isatin-Sepharose, we have investigated the distribution of [(3)H]isatin specific binding sites in the rat brain, characterized their K(d) and B(max), and identified some individual brain isatin binding proteins. The binding of [(3)H]isatin to rat brain sections was saturable and characterized by K(d) values (of 0.2-0.3 microM) consistent with physiological concentrations. The highest B(max) was found in the hypothalamus, consistent with a role in stress. In most brain regions, the homologous inhibition of [(3)H]isatin binding by increasing concentrations of cold isatin demonstrated complex behavior suggesting involvement of various binding proteins characterized by different affinity to isatin. Affinity chromatography of Triton X-100 lysates of whole-brain homogenates on 5-aminocaproyl-isatin-Sepharose followed by subsequent proteomic analysis resulted in identification of 25 individual proteins, including glyceraldehyde-3-phosphate dehydrogenase, one of few previously reported isatin binding proteins, and a group of cytoskeleton-related proteins. These binding sites may be related to the known antiproliferative and proapoptotic activities of isatin.

De novo mutation of emopamil binding protein (EBP) gene in a girl with Conradi-Hünermann-Happle syndrome.

Conradi-Hünermann-Happle syndrome is a rare X-linked dominant syndrome affecting the skin, skeletal system, and eyes. Here, we report on a female patient with a de novo heterozygous missense mutation c.301C>T (p.Trp101Arg) of the EMP (emopamil binding protein) gene.

CXCL5 Facilitates Melanoma Cell-Neutrophil Interaction and Lymph Node Metastasis.

Chemokines influence tumor metastasis by targeting tumor, stromal, and hematopoietic cells. Characterizing the chemokine mRNA expression profile of human primary melanoma samples, we found CXCL5 significantly up-regulated in stage T4 primary melanomas when compared to thin melanomas (T1 stage). To characterize the role of CXCL5 in melanoma progression, we established a metastasizing murine xenograft model using CXCL5-overexpressing human melanoma cells. CXCL5 had no effect on melanoma proliferation in vitro and on primary tumor growth in vivo, but CXCL5-overexpressing tumors recruited high amounts of neutrophils and exhibited significantly increased lymphangiogenesis in our severe combined immune-deficient mouse model. Recruited neutrophils were found in close proximity to or within lymphatic vessels, often in direct contact with melanoma cells. Clinically, CXCL5-overexpressing melanomas had significantly increased lymph node metastases. We were able to translate these findings to human patient samples and found a positive correlation between CXCL5 expression, numbers of neutrophils in stage T4 primary melanoma, and the occurrence of subsequent locoregional metastasis.

Reconstrução do braço com retalho miocutâneo do músculo grande dorsal após ressecção de sarcomas: relato de dois casos e descrição da técnica cirúrgica / Arm reconstruction with myocutaneous flap of the latissimus dorsi muscle after resection of sarcomas: report of two cases and description of the surgical technique

Os sarcomas de partes moles são neoplasias malignas raras originadas do mesênquima, mais comumente encontradas em membros. A ressecção cirúrgica com margens livres acima de 1cm é fundamental para obter a cura do paciente. A radioterapia pode ser combinada ao tratamento em casos selecionados. A reconstrução dos membros superiores após ressecções alargadas é um desafio. O retalho miocutâneo do músculo grande dorsal (RMGD) é uma opção em casos de lesões em membros superiores, sobretudo terço proximal e médio do braço, com preservação da função do membro e fechamento primário da área de ressecção. Relatamos dois casos de ressecção e reconstrução do braço utilizando RMGD com foco na descrição da técnica cirúrgica.

Soft tissue sarcomas are rare malignant neoplasms arising from the mesenchyme, most commonly found in the limbs. Surgical resection with free margins greater than 1 cm is essential to obtain a cure for the patient. Radiation therapy can be combined with treatment in selected cases. Reconstruction of the upper limbs after extended resections is a challenge. The latissimus dorsi myocutaneous flap (LDMF) is an option in injuries to the upper limbs, especially the proximal and middle thirds of the arm, with preservation of limb function and primary closure of the resection area. We report two cases of arm resection and reconstruction using LDMF, focusing on the surgical technique description.

Expression pattern of NOGO and NgR genes during human development.

Nogo protein has been identified as the component of central nervous system (CNS) myelin that limits axonal regeneration. We investigated the expression of the genes encoding Nogo and its receptor, NgR, between weeks eight and 23 of human embryonic development, by quantitative radioactive in situ hybridization. At 8 weeks, we detected NOGO and NgR transcripts in developing neuronal and non-neuronal structures. We focused on two different structures: the brain and the dental germs. During this period of development, NOGO and NgR transcripts colocalized in the cortical and ventricular zones of the brain, with expression strongest for these two genes in the postmitotic cells of the cortical plate. In developing dental germs, NgR was more strongly expressed than NOGO at 16 and 21 weeks. NOGO and NgR were expressed in zones of epithelium-mesenchyme interaction, which induce the differentiation of ameloblasts/odontoblasts. These genes were expressed most strongly in differentiated cells.

Activin A is anti-lymphangiogenic in a melanoma mouse model.

Melanoma spreads primarily to the sentinel lymph nodes, and its risk correlates with lymphangiogenesis, which is mainly driven by vascular endothelial growth factor (VEGF)-C. However, anti-lymphangiogenic factors are poorly characterized. We have shown in a melanoma model that Wnt1 reduces lymphangiogenesis by reducing VEGF-C expression. Screening this model for additional potentially anti-lymphangiogenic factors identified increased activin A expression and reduced expression of the antagonist, follistatin (FST), in Wnt1(+) cells. Activin A is known to reduce blood vessel formation, but the effects on lymphangiogenesis are unknown. Here we show that human primary melanoma expresses significantly higher levels of activin A and lower levels of FST compared with nevi and melanoma metastasis. Using our mouse model with melanoma cells overexpressing Wnt1, FST, Wnt1/FST, or the inhibin ßA subunit (INHBA, resulting in activin A expression), we found both activin A and Wnt1 to reduce lymphangiogenesis. Whereas Wnt1 also reduced metastasis, this was not seen with activin A. In vitro, activin A phosphorylated SMAD2 in both melanoma and lymphatic endothelium but, although it reduced sprouting of lymphatic endothelium, it enhanced the migration of melanoma cells. In conclusion, activin A is an anti-lymphangiogenic factor, but because of its pleiotropic effects on cell mobility it appears not suitable as a pharmacological target.

Localization of [3H]nicotine, [3H]cytisine, [3H]epibatidine, and [125I]alpha-bungarotoxin binding sites in the brain of Macaca mulatta.

We determined the localization of [(3)H]nicotine, [(3)H]cytisine, [(3)H]epibatidine, and [(125)I]alpha-bungarotoxin binding sites in the brain of rhesus monkey by means of receptor autoradiography. The labelings by [(3)H]nicotine, [(3)H]cytisine, and [(3)H]epibatidine were highly concordant, except for epibatidine. Layer IV of some cortical areas, most thalamic nuclei, and presubiculum displayed high levels of labeling for the three ligands. Moderate levels of binding were detected in the subiculum, the septum, and the mesencephalon. Low levels were present in layers I-II and VI of the cortex, the cornu Ammonis, the dentate gyrus, and the amygdala. In addition, the level of epibatidine labeling was very high in the epithalamic nuclei and the interpeduncular nucleus, whereas labeling by nicotine and cytisine was very weak in the same regions. The distribution of [(125)I]alpha-bungarotoxin binding differed from the binding of the three agonists. The labeling was dense in layer I of most cortical areas, dentate gyrus, stratum lacunosum-moleculare of CA1 field, several thalamic nuclei, and medial habenula. A moderate labeling was found in layers V and VI of the prefrontal and frontal cortices, layer IV of primary visual cortex, amygdala, septum, hypothalamus, and some mesencenphalic nuclei. A weak signal was also detected in subiculum, claustrum, stratum oriens, and stratum lucidum of cornu Ammonis and also in some mesencephalic nuclei. The distribution of nicotine, cytisine, and epibatidine bindings corresponds broadly to the patterns observed in rodents, with the marked exception of the epithalamus. However, in monkey, those distributions match the distribution of alpha2 messenger RNA, rather than that of alpha4 transcripts as it exists in rodent brains. The distribution of the binding sites for alpha-bungarotoxin is larger in the brain of rhesus monkeys than in rodent brain, suggesting a more important role of alpha7 receptors in primates.

Encuentros con la diferencia: la pluralidad en las experiencias de jóvenes universitarios / Encounters with the difference: the plurality in the experiences of university students

Resumen Este artículo se desprende de la tesis "Relaciones sociales en la universidad: poder, conflicto y pluralidad entre jóvenes", presentada por la autora, Ana María Arias Cardona, como requisito para optar al título de Doctora en Ciencias Sociales: Niñez y Juventud, en el Centro de Estudios Avanzados en Niñez y Juventud de la Universidad De Manizales-CINDE, la cual se centra en universitarios y analiza formas simbólicas de exclusión. Se enfoca en la categoría "pluralidad", cuyo objetivo es comprender cómo configuran los jóvenes su encuentro con la diferencia, cómo afrontan la diversidad en sus relaciones. El diseño es cualitativo, el método hermenéutico y las técnicas empleadas talleres y entrevistas. Participaron 119 jóvenes de dos universidades públicas y dos privadas de Antioquia (Colombia). Los resultados se agrupan en tres subcategorías: "Todos somos 'el otro' del otro: la diferencia como déficit"; "Preferir no es excluir: ¿optar por unos sin vulnerar a otros?"; y "Procesos de inclusión que evidencian movilizaciones solidarias". Esto permite concluir que la diversidad se lee como algo negativo, y que es difuso el límite respecto a la discriminación, pues dichos actos se han "naturalizado".

Abstract This article summarizes the highlights of a thesis that analyses the symbolic ways of exclusion among university students. It focuses on the "plurality" category which objective was to understand how young frame their encounter with difference, how they confront diversity in their relationships. The design was qualitative, the hermeneutical method was used along with workshops and interviews techniques. 119 young people participated, from two public university and two private university in Antioquia (Colombia). The results are grouped into three subcategories: "We are all 'the other of the other: difference as deficit"; "To prefer is not to exclude: How to opt for certain ones without harming others?" and inclusion processes that show solidary mobilizations: which allows to conclude that diversity is read as something negative, that the limit regarding discrimination is diffuse and such, since those acts have been "naturalized".

Absence of the gut microbiota enhances anxiety-like behavior and neuroendocrine response to acute stress in rats.

BACKGROUND AND AIMS: Establishment of the gut microbiota is one of the most important events in early life and emerging evidence indicates that the gut microbiota influences several aspects of brain functioning, including reactivity to stress. To better understand how the gut microbiota contributes to a vulnerability to the stress-related psychiatric disorders, we investigated the relationship between the gut microbiota, anxiety-like behavior and HPA axis activity in stress-sensitive rodents. We also analyzed the monoamine neurotransmitters in the brain upper structures involved in the regulation of stress and anxiety. METHODS: Germfree (GF) and specific pathogen free (SPF) F344 male rats were first subjected to neurological tests to rule out sensorimotor impairments as confounding factors. Then, we examined the behavior responses of rats to social interaction and open-field tests. Serum corticosterone concentrations, CRF mRNA expression levels in the hypothalamus, glucocorticoid receptor (GR) mRNA expression levels in the hippocampus, and monoamine concentrations in the frontal cortex, hippocampus and striatum were compared in rats that were either exposed to the open-field stress or not. RESULTS: GF rats spent less time sniffing an unknown partner than SPF rats in the social interaction test, and displayed a lower number of visits to the aversive central area, and an increase in latency time, time spent in the corners and number of defecations in the open-field test. In response to the open-field stress, serum corticosterone concentrations were 2.8-fold higher in GF than in SPF rats. Compared to that of SPF rats, GF rats showed elevated CRF mRNA expression in the hypothalamus and reduced GR mRNA expression in the hippocampus. GF rats also had a lower dopaminergic turnover rate in the frontal cortex, hippocampus and striatum than SPF rats. CONCLUSIONS: In stress-sensitive F344 rats, absence of the gut microbiota exacerbates the neuroendocrine and behavioral responses to acute stress and the results coexist with alterations of the dopaminergic turnover rate in brain upper structures that are known to regulate reactivity to stress and anxiety-like behavior.

Conflicto y educación superior: narrativas y vivencias de jóvenes universitarios estudiantes de ciencias sociales y humanas / Conflict and Higher Education: Narratives and Experiences of Young University Students of Social and Human Sciences

Resumen La investigación se realizó con un enfoque cualitativo, a partir de un método hermenéutico, con 119 estudiantes de cuatro universidades del departamento de Antioquia (Colombia). Los datos fueron construidos por medio de talleres con técnicas interactivas y de entrevistas semi-estructuradas, con el objetivo de caracterizar las expresiones del conflicto en las relaciones entre jóvenes, particularmente, los sentidos, las causas, las consecuencias que le otorgan y la manera como le hacen frente a sus conflictos. Los hallazgos se centran en: a) la tensión entre la evasión individualista y la movilización por el "entre nos"; b) la polarización entre el "deber ser" y el "real hacer"; c) la tendencia de los estudiantes a homologar conflicto y violencia, y d) el difícil tránsito de la queja a la responsabilidad subjetiva. Estos resultados dan cuenta de movimientos pendulares que se presentan frente a lo complejo del conflicto y sus aristas, y evidencian la naturalización de expresiones violentas, la banalización de mecanismos de exclusión, la precariedad respecto al uso de estrategias positivas para afrontar situaciones problemáticas, la poca congruencia entre lo que se piensa y lo que se hace, y la falta de responsabilidad por parte de muchos jóvenes que catalogan las causas del conflicto como elementos ajenos a ellos. Desde la perspectiva de los estudiantes, en el contexto universitario, el conflicto tiene expresiones más sutiles, menos específicas y, además, presentan dificultades para realizar una reflexión positiva sobre éste, pues no lo ven como una oportunidad, sino que suelen derivarlo en situaciones de violencia simbólica.

Abstract This paper is one of the products of a doctoral thesis, which inquired for power, conflict and pluralism in relationships among university students. Its content is specifically focused on presenting the results of a category devoted for "conflict". The research was conducted with a qualitative approach, from a hermeneutical method, with 119 students from four universities in the department of Antioquia (Colombia). The data were taken through workshops with interactive techniques and semi-structured interviews to understand conceptions, meanings, causes and types of coping strategies that students faced in the conflict among them. The findings are mainly focused on: a) the stress between the individualist evasion and the mobilization by the "between us", b) The polarization between the "must be" and the "doing for a real", c) The tendency of students to standardize conflict and violence, and d) the difficult transition from the complaint to the subjective responsibility. The results show pendulum movements arisen from the complexity of the conflict and its edges, and evidence the naturalization of violent expressions, trivialization of exclusion mechanisms, pre-cariousness regarding the use of positive strategies to face problematic situations, the little congruence between what is thought and what is done, and the lack of responsibility on the part of many young people who have defined the causes of the conflict as external elements from them. From students' point of view, in relation to the university context, the conflict has expressions more subtle, less specific and, in addition, it is not easy to make a positive reflection about it, because for them it is not an opportunity, but it is a product of symbolic violence.