Effects of a veterinary functional music-based enrichment program on the psychophysiological responses of farm pigs.

Intensification of swine production can predispose pigs to chronic stress, with adverse effects on the neuroendocrine and immune systems that can lead to health problems, poor welfare, and reduced production performance. Consequently, there is an interest in developing tools to prevent or eliminate chronic stress. Music is widely used as a therapeutic strategy for stress management in humans and may have similar benefits in non-human animals. This study evaluated the effects of a music-based auditory enrichment program in pigs from a multidimensional perspective by assessing psychophysiological responses. Two experimental groups of 20 pigs each were selected for the study: one enriched, exposed to a program of functional veterinary music designed for pigs, and a control group without auditory stimulation. Qualitative behavior assessment (QBA) and skin lesions indicative of agonistic behavior were used to evaluate the psychological determinants underlying the observed behaviors. Physiological assessment included hemograms, with the determination of the neutrophil:lymphocyte ratio and daily measurements of cortisol and salivary alpha-amylase levels. The results demonstrated a positive effect of a music-based auditory program on psychophysiological responses. Therefore, this strategy developed for environmental enrichment may be beneficial in reducing stress and contributing to the welfare and health of pigs under production conditions.

CRF-R1 Antagonist Treatment Exacerbates Circadian Corticosterone Secretion under Chronic Stress, but Preserves HPA Feedback Sensitivity.

Despite promising initial reports, corticotropin-releasing factor receptor type-1 (CRF-R1) antagonists have mostly failed to display efficacy in clinical trials for anxiety or depression. Rather than broad-spectrum antidepressant/anxiolytic-like drugs, they may represent an 'antistress' solution for single stressful situations or for patients with chronic stress conditions. However, the impact of prolonged CRF-R1 antagonist treatments on the hypothalamic-pituitary-adrenal (HPA) axis under chronic stress conditions remained to be characterized. Hence, our study investigated whether a chronic CRF-R1 antagonist (crinecerfont, formerly known as SSR125543, 20 mg·kg-1·day-1 ip, 5 weeks) would alter HPA axis basal circadian activity and negative feedback sensitivity in mice exposed to either control or chronic stress conditions (unpredictable chronic mild stress, UCMS, 7 weeks), through measures of fecal corticosterone metabolites, plasma corticosterone, and dexamethasone suppression test. Despite preserving HPA axis parameters in control non-stressed mice, the 5-week crinercerfont treatment improved the negative feedback sensitivity in chronically stressed mice, but paradoxically exacerbated their basal corticosterone secretion nearly all along the circadian cycle. The capacity of chronic CRF-R1 antagonists to improve the HPA negative feedback in UCMS argues in favor of a potential therapeutic benefit against stress-related conditions. However, the treatment-related overactivation of HPA circadian activity in UCMS raise questions about possible physiological outcomes with long-standing treatments under ongoing chronic stress.

Características de los sangrados en niños con hemofilia en un centro de referencia en Colombia / Characteristics of bleeding in children with hemophilia in a reference center in Colombia

Resumen Introducción: La hemofilia es el trastorno hemorrágico congénito más frecuente en los varones, los pacientes con enfermedad severa pueden tener sangrados espontáneos que llevan a discapacidad. Objetivo: Describir las características de los sangrados y los aspectos clínicos y demográficos de un grupo de pacientes con diagnóstico de hemofilia en un centro de referencia de la ciudad de Bogotá. Materiales y métodos: Estudio descriptivo de serie de casos, en menores de 18 años con hemofilia, entre mayo 1 a diciembre 31 de 2014. Resultados: Se incluyeron 51 pacientes, 33/51 tuvieron sangrado, 109 sangrados, el sangrado más frecuente fue hemartrosis y en niños con anticuerpos inhibidores. 22 pacientes tenían hemofilia severa, 18 moderada y 11 leve. 18/22 pacientes severos sangraron y tuvieron 87 sangrados, 14/18 (77%) pacientes con artropatía tuvieron sangrado, con 74 eventos en total, 19/33 pacientes sin artropatía tuvieron 35 eventos. El grupo con mayor frecuencia de sangrados tenía entre 5 y 9 años. De los 81 episodios traumáticos, la mayoría fueron jugando y haciendo deporte; Se presentaron 19 sangrados espontáneos y nueve relacionados con procedimientos. 84 sangrados fueron en temporada escolar y 25 en vacaciones. Al momento de los sangrados en 76 episodios estaban acompañados por padres o familiares y 69 episodios ocurrieron en el hogar (62,4%). Conclusiones: Los sangrados fueron más frecuentes en niños con anticuerpos inhibidores, enfermedad severa, con artropatía, en temporada escolar y estando acompañados. No hubo mayor frecuencia de sangrados en aquellos con disfunción familiar.

Abstract Introduction: Hemophilia is the most common congenital hemorrhagic disorder in males. Patients with severe disease may have spontaneous bleeding leading to disability. Objective: To describe the bleedings and clinical features of children diagnosed with hemophilia and treated in a reference center in Bogotá. Methodology:Descriptive study of a case series of children (under 18 years) diagnosed with hemophilia, between May 1st and December 31th 2014. Results: Fifty-one patients were included, 33/51 experienced 109 bleedings. Most common type were hemarthrosis and children with inhibitory antibodies had more bleeding episodes. Twenty-two patients had severe hemophilia, 18 moderate and 11 mild. In 18 of 22 severe patients, there were 87 bleeding episodes. 14/33 patients with arthropathy (77%) experienced 74 bleeding events while the rest referred only 35. Patients between 5 to 9 years old had the highest frequency of bleeding. Among the 81 traumatic episodes, most frequent activities were playing and sport practicing; there were 19 spontaneous bleedings and nine were related to procedures. 89 bleeds occurred during school days and 25 on vacation. At the time of bleeding, in 76 episodes, patients were accompanied by family members. Conclusions: Bleeding was more frequent in children with severe disease, with arthropathy, during school time and while being accompanied. Bleedings did not occurred with a higher frequency in children with family dysfunction.

Decline of hippocampal stress reactivity and neuronal ensemble coherence in a mouse model of depression.

Dysregulations of stress systems, especially the hypothalamo-pituitary-adrenal (HPA) axis, have been commonly reported in major depression. Consistent results emphasized the role of the hippocampus in regulating stress systems and restoring an operative control on HPA axis following antidepressant treatments. However, very little is known about how the hippocampus integrates stress-related information and reacts to stressors beforehand. We therefore aimed to assess activations of hippocampal neuronal ensembles during stress-related experiences and evaluated the effects of a mouse model of depression, the Unpredictable Chronic Mild Stress (UCMS), and an antidepressant treatment (fluoxetine, 20mgkg(-1)day(-1), ip) in BALB/cByJ mice. The UCMS induced a depression-like syndrome characterized by a reduced weight gain, a progressive deterioration of the coat, an altered stress-coping strategy in behavioural tests and HPA axis dysregulations. Chronic fluoxetine had no effect in control non-stressed mice per se but reversed the syndrome induced by the UCMS, including an improvement of the HPA-system alterations. Neuronal activation was then assessed by immediate early-gene (c-fos) expression in different subfields of the CA3 and dentate gyrus (DG) along the dorso-ventral axis of the hippocampus, as they can support different computational functions. Our results showed that the hippocampus reacts to stressors by adjusting activations of cell ensembles. A pre-treatment with dexamethasone (DEX), a glucocorticoid receptor (GR) agonist that produced a delayed inhibition of the HPA axis activity, reduced novelty-related activations in the proximal CA3 (CA3c) and the DG of the dorsal hippocampus. All these effects were compromised by the UCMS, particularly by altering activation coherences within the dorsal CA3-DG network, but were rescued by chronic fluoxetine. Our study indicates therefore that variations of CA3-DG cell ensemble activation may contribute to stress integration in the hippocampus and that dysfunctions of this process may foster HPA-system dysregulations and depression-related states. It suggests that pharmacological interventions aiming to consolidate CA3-DG neural network might improve stress reactivity and possibly benefit to patients with major depression.

The BDNF Val(66)Met polymorphism is associated with escitalopram response in depressed patients.

BACKGROUND: The brain-derived neurotrophic factor (BDNF) gene is a candidate gene in therapeutic responses to antidepressants. The aim of the study was to determine the effects of BDNF allelic variability on responses to escitalopram treatment at 3 weeks after treatment initiation and at a 6-week endpoint. METHODS: We included 187 Caucasian subjects with depression; 153 completed the 6-week study. Clinical evaluation was performed using the Montgomery and Asberg Depression Rating Scale (MADRS) before and after 3-6 weeks of treatment. RESULTS: After 3 weeks of treatment, we saw significantly better treatment responses in the Met carriers and greater antidepressant resistance among the Val/Val homozygotes. Relative to Val/Val homozygous (59.78 %), a significantly greater proportion of subjects Met-carriers (77.94 %) responded to escitalopram treatment (χ (2) = 5.88, p = 0.015). After 6 weeks, we found the same pattern of results but this effect did not reach statistical significance (χ (2) = 2.07, p = 0.15). CONCLUSION: These findings highlight a significant association between the BDNF valine to methionine substitution (Val(66)Met) polymorphism and the treatment response to escitalopram in a Caucasian population of severely depressed inpatients.

Deficit in BDNF does not increase vulnerability to stress but dampens antidepressant-like effects in the unpredictable chronic mild stress.

Despite growing evidences of an association between brain-derived neurotrophic factor (BDNF) and antidepressant effects, the neurotrophic hypothesis of depression is challenged by the paucity of direct links between BDNF deficit and depressive-like behaviors. The unpredictable chronic mild stress (UCMS) paradigm might take our understanding a step further by examining whether a decrease in bdnf expression can lead to enhanced vulnerability to stress and prevent antidepressant efficacy in all or specific UCMS-induced alterations. Wild-type bdnf(+/+) and heterozygous bdnf(+/-) mice were exposed to an 8-week UCMS regimen and, from the third week onward, treated with either vehicle or imipramine (20mg/kg/day, ip). Physical, behavioral and biological (plasma corticosterone levels, bdnf expression in the dentate gyrus) measures were further analyzed regarding to the genotype and the treatment. Heterozygous bdnf(+/-) mice displayed hyperactivity and increase of body weight but no enhancement of the sensitivity to stress exposure in all the measures investigated here. In contrast, while imipramine treatment reduced anxiety-like behaviors in the novelty-suppressed feeding test in both genotypes, it decreased aggressiveness in the resident/intruder test and immobility in the tail suspension test in wild-type but not in heterozygous mice. Furthermore, imipramine induced a twofold increase of bdnf expression in the dentate gyrus in both genotypes, while bdnf(+/-) mice displayed roughly half-reduced level for the same treatment. In summary, we demonstrate here that depletion in BDNF dampened the antidepressant effects in several behaviors but failed to increase vulnerability to chronic stress exposure.

Corticolimbic transcriptome changes are state-dependent and region-specific in a rodent model of depression and of antidepressant reversal.

Gene microarrays may enable the elucidation of neurobiological changes underlying the pathophysiology and treatment of major depression. However, previous studies of antidepressant treatments were performed in healthy normal rather than 'depressed' animals. Since antidepressants are devoid of mood-changing effects in normal individuals, the clinically relevant rodent transcriptional changes could remain undetected. We investigated antidepressant-related transcriptome changes in a corticolimbic network of mood regulation in the context of the unpredictable chronic mild stress (UCMS), a naturalistic model of depression based on socio-environmental stressors. Mice subjected to a 7-week UCMS displayed a progressive coat state deterioration, reduced weight gain, and increased agonistic and emotion-related behaviors. Chronic administration of an effective (fluoxetine) or putative antidepressant (corticotropin-releasing factor-1 (CRF1) antagonist, SSR125543) reversed all physical and behavioral effects. Changes in gene expression differed among cingulate cortex (CC), amygdala (AMY) and dentate gyrus (DG) and were extensively reversed by both drugs in CC and AMY, and to a lesser extent in DG. Fluoxetine and SSR125543 also induced additional and very similar molecular profiles in UCMS-treated mice, but the effects of the same drug differed considerably between control and UCMS states. These studies established on a large-scale that the molecular impacts of antidepressants are region-specific and state-dependent, revealed common transcriptional changes downstream from different antidepressant treatments and supported CRF1 targeting as an effective therapeutic strategy. Correlations between UCMS, drug treatments, and gene expression suggest distinct AMY neuronal and oligodendrocyte molecular phenotypes as candidate systems for mood regulation and therapeutic interventions.

Multifaceted strain-specific effects in a mouse model of depression and of antidepressant reversal.

Etiopathogenesis of depression and the cause of insensitivity to treatment remain poorly understood, although genetic makeup has been established as a contributing factor. The isogenicity of inbred mouse strains provides a useful tool for investigating the link between genes and behavior or drug response. Hence, our aim was to identify inbred mouse strains (among A/J, BALB/c, C3H, C57BL/6, CBA, DBA and FVB) sensitive to a 9-week period of unpredictable chronic mild stress (UCMS) and, from the fifth week onward, to the reversal effect of an antidepressant (AD) (imipramine, 20mg/kg/day i.p.) on various depression-related changes: physical, behavioral and neuroendocrine states. UCMS induced a significant deterioration of the coat state (in all the strains), blunted emotional reactivity in the novelty-suppressed feeding (NSF) test (A/J, BALB/c, C57BL/6), and changes in the level of fecal corticosterone metabolites (BALB/c, C57BL/6, DBA, FVB). Imipramine treatment reversed the UCMS-induced alterations of the coat state (BALB/c, DBA), in the NSF test (A/J, BALB/c, C57BL/6) and in fecal corticosterone metabolites (BALB/c, C57BL/6). C3H, CBA and FVB mice were irresponsive to imipramine treatment. It is noteworthy that UCMS-induced physical or behavioral changes occurred without hypothalamo-pituitary-adrenal (HPA) axis alterations in some strains (A/J, C3H, CBA), although the AD-induced reversal of these changes in BALB/c and C57BL/6 was associated with HPA axis normalization. Finally, UCMS is shown to discriminate various alterations and to replicate in a strain-dependent manner diverse profiles reminiscent of human disease subtypes. UCMS may thus enable the selection of strains suitable for investigating specific depression-related features and could be an appropriate model for identifying genetic factors associated with increased vulnerability, specific symptoms of affective disorders, and AD resistance.

Drug-dependent requirement of hippocampal neurogenesis in a model of depression and of antidepressant reversal.

BACKGROUND: Depression and anxiety disorders have been linked to dysfunction of the hypothalamo-pituitary-adrenal (HPA) axis and structural changes within the hippocampus. Unpredictable chronic mild stress (UCMS) can recapitulate these effects in a mouse model, and UCMS-induced changes, including downregulation of hippocampal neurogenesis, can be reversed by antidepressant (AD) treatment. We investigated causality between changes in hippocampal neurogenesis and the effects of both chronic stress and chronic ADs. METHODS: Mice were treated with either a sham procedure or focal hippocampal irradiation to disrupt cell proliferation before being confronted with 5 weeks of UCMS. From the third week onward, we administered monoaminergic ADs (imipramine, fluoxetine), the corticotropin-releasing factor 1 (CRF(1)) antagonist SSR125543, or the vasopressin 1b (V(1b)) antagonist SSR149415 daily. The effects of UCMS regimen, AD treatments, and irradiation were assessed by physical measures (coat state, weight), behavioral testing (Splash test, Novelty-Suppressed feeding test, locomotor activity), and hippocampal BrdU labeling. RESULTS: Our results show that elimination of hippocampal neurogenesis has no effect on animals' sensitivity to UCMS in several behavioral assays, suggesting that reduced neurogenesis is not a cause of stress-related behavioral deficits. Second, we present evidence for both neurogenesis-dependent and -independent mechanisms for the reversal of stress-induced behaviors by AD drugs. Specifically, loss of neurogenesis completely blocked the effects of monoaminergic ADs (imipramine, fluoxetine) but did not prevent most effects of the CRF(1) and the V(1b) antagonists. CONCLUSIONS: Hippocampal neurogenesis might thus be used by the monoaminergic ADs to counteract the effects of stress, whereas similar effects could be achieved by directly targeting the HPA axis and related neuropeptides.

Factores protectores y de riesgo para VIH/SIDA en mujeres de Cali, Colombia / Protective and risk factors for HIV/AIDS in women from Cali, Colombia

El propósito de este estudio fue contribuir con la promoción de la salud de las mujeres de la ciudad de Cali; adicionalmente sensibilizar a las mujeres participantes sobre la problemática de la infección por el VIH/SIDA y otras ITS. Objetivos: 1) Explorar la presencia de factores protectores y de riesgo para VIH/SIDA y otras ITS en las mujeres participantes del estudio; 2) Determinar la vulnerabilidad y percepción de riesgo de las mujeres a la infección por VIH y otras ITS. Se utilizó un diseño transversal por encuesta. En total participaron 312 mujeres de las 21 comunas de Cali en un rango de edad de 12 a 76 años. El 61 por ciento de las mujeres de la muestra eran sexualmente activas, y de éstas el 84 por ciento refirieron relaciones heterosexuales; el 11 por ciento había tenido relaciones sexuales con más de una persona en los últimos 12 meses. El 45 por ciento de las mujeres percibió infiel a su pareja sexual. El 51 por ciento de las mujeres se sienten cómodas hablando con su pareja de su vida sexual, este porcentaje disminuye a 40 por ciento cuando hablan con su pareja sobre sus necesidades en la relación y decrece al 29 por ciento al hablar sobre la existencia de otras compañeras sexuales. El 9 por ciento reportó violencia sexual por su pareja. El 70 por ciento se percibió vulnerable al VIH/SIDA, sin embargo, sólo el 31 por ciento de las mujeres sexualmente activas usó el condón por temor al SIDA. La autoestima de las mujeres de la muestra fue alta, la mayoría sostenía relaciones monogámicas y no usaban ni compartían agujas para inyección endovenosa. Se discuten aspectos relacionados con el empoderamiento de las mujeres como estrategia para dar mayor énfasis a la promoción de la salud en lugar de la prevención de la enfermedad.