Neurotrophins Role in Depression Neurobiology: A Review of Basic and Clinical Evidence

Depression is a neuropsychiatric disorder affecting a huge percentage of the active population especially in developed countries. Research has devoted much of its attention to this problematic and many drugs have been developed and are currently prescribed to treat this pathology. Yet, many patients are refractory to the available therapeutic drugs, which mainly act by increasing the levels of the monoamines serotonin and noradrenaline in the synaptic cleft. Even in the cases antidepressants are effective, it is usually observed a delay of a few weeks between the onset of treatment and remission of the clinical symptoms. Additionally, many of these patients who show remission with antidepressant therapy present a relapse of depression upon treatment cessation. Thus research has focused on other possible molecular targets, besides monoamines, underlying depression. Both basic and clinical evidence indicates that depression is associated with several structural and neurochemical changes where the levels of neurotrophins, particularly of brain-derived neurotrophic factor (BDNF), are altered. Antidepressants, as well as other therapeutic strategies, seem to restore these levels. Neuronal atrophy, mostly detected in limbic structures that regulate mood and cognition, like the hippocampus, is observed in depressed patients and in animal behavioural paradigms for depression. Moreover, chronic antidepressant treatment enhances adult hippocampal neurogenesis, supporting the notion that this event underlies antidepressants effects. Here we review some of the preclinical and clinical studies, aimed at disclosing the role of neurotrophins in the pathophysiological mechanisms of depression and the mode of action of antidepressants, which favour the neurotrophic/neurogenic hypothesis

Chimeric NANOG repressors inhibit glioblastoma growth in vivo in a context-dependent manner

Targeting stemness promises new therapeutic strategies against highly invasive tumors. While a number of approaches are being tested, inhibiting the core transcription regulatory network of cancer stem cells is an attractive yet challenging possibility. Here we have aimed to provide the proof of principle for a strategy, previously used in developmental studies, to directly repress the targets of a salient stemness and pluripotency factor: NANOG. In doing so we expected to inhibit the expression of so far unknown mediators of pro-tumorigenic NANOG function. We chose NANOG since previous work showed the essential requirement for NANOG activity for human glioblastoma (GBM) growth in orthotopic xenografts, and it is apparently absent from many adult human tissues thus likely minimizing unwanted effects on normal cells. NANOG repressor chimeras, which we name NANEPs, bear the DNA-binding specificity of NANOG through its homeodomain (HD), and this is linked to transposable human repressor domains. We show that in vitro and in vivo, NANEP5, our most active NANEP with a HES1 repressor domain, mimics knock-down (kd) of NANOG function in GBM cells. Competition orthotopic xenografts also reveal the effectiveness of NANEP5 in a brain tumor context, as well as the specificity of NANEP activity through the abrogation of its function via the introduction of specific mutations in the HD. The transcriptomes of cells expressing NANEP5 reveal multiple potential mediators of pro-tumorigenic NANEP/NANOG action including intercellular signaling components. The present results encourage further studies on the regulation of context-dependent NANEP abundance and function, and the development of NANEP-based anti-cancer therapies.This work was supported by a James McDonnell Brain Cancer Award, Fondation Eclosion funds and by the Département d’Instruction Publique de Genève to ARA. C.M. and M.K. were fellows of the ITN-EU networks CAPPELLA and HEALING, respectively

Alimentary consumption of women active and physically inactive in postmenopausal period

El objetivo del presente estudio fue observar el consumo alimenticio y la prevalencia del síndrome metabólico en mujeres activas e inactivas físicamente en la post-menopausia. La muestra fue compuesta de 83 mujeres, pertenecientes al municipio de Natal (Río Grande do Norte) de Brasil; pertenecientes al programa “Natal Activa”, con edad media de 59,7 ± 8,08 años. Se aplicó un cuestionario para analizar la frecuencia del consumo alimenticio, un cuestionario de actividad física, una anamnesis clínica, una evaluación antropométrica, exámenes bioquímicos y un diagnóstico del Síndrome Metabólico. Los resultados mostraron que las mujeres activas consumen más alimentos protectores que las mujeres inactivas. La prevalencia del síndrome metabólico en las mujeres inactivas fue mayor que en las mujeres activas, además, existe la necesidad de cambiar dichos hábitos en esta población, pudiéndose alcanzar así mayores cambios corporales y metabólicos, minimizando la incidencia del síndrome metabólico en los dos gruposThe aim of this study was to observe the dietary intake and the prevalence of metabolic syndrome in physically active and inactive women in the postmenopause. The sample was composed of 83 women, from the municipality of Natal (Rio Grande do Norte) in Brazil; from the "Natal Active" program, with an average age of 59.7 ± 8.08 years old. A questionnaire to analyze the frequency of food consumption, physical activity questionnaire, a clinical anamnesis, anthropometric evaluation, biochemical tests and a diagnosis of metabolic syndrome was applied. The results showed that active women consume more protective foods than inactive women. The prevalence of metabolic syndrome in inactive women was higher than in active women, in addition, there is a need to change those habits in this population, being able thus to achieve greater physical and metabolic changes, minimizing the incidence of metabolic syndrome in both group

DEMON: a Proposal for a Satellite-Borne Experiment to study Dark Matter and Dark Energy

We outline a novel satellite mission concept, DEMON, aimed at advancing our comprehension of both dark matter and dark energy, taking full advantage of two complementary methods: weak lensing and the statistics of galaxy clusters. We intend to carry out a 5000 sqdeg combined IR, optical and X-ray survey with galaxies up to a redshift of z~2 in order to determine the shear correlation function. We will also find ~100000 galaxy clusters, making it the largest survey of this type to date. The DEMON spacecraft will comprise one IR/optical and eight X-ray telescopes, coupled to multiple cameras operating at different frequency bands. To a great extent, the technology employed has already been partially tested on ongoing missions, therefore ensuring improved reliability.Comment: 12 pages, 3 figures, accepted for publication in the SPIE conference proceeding

Defining a standard set of health outcomes for patients with relapsing-remitting multiple sclerosis

Outcome measurement; Patient-centred care; Relapsing-remitting multiple sclerosisMedición de resultados; Atención centrada en el paciente; Esclerosis múltiple remitente-recurrenteMesura de resultats; Atenció centrada en el pacient; Esclerosi múltiple recurrent-remissióBackground Standardizing health outcomes is challenging in clinical management, but it also holds the potential for creating a healthcare system that is both more effective and efficient. The aim of the present study is to define a standardized set of health outcomes for managing Relapsing-Remitting Multiple Sclerosis (RRMS). Methods The project was led and coordinated by a multidisciplinary scientific committee (SC), which included a literature review, a patient-focused group, three nominal group meetings, and two SC meetings. Results 36 outcome variables were included in the standard set: 24 clinical (including weight, smoking habit, comorbidities, disability, mobility, diagnosis of secondary progressive multiple sclerosis, relapsed-related variables, radiological variables, cognitive status and disease-related symptoms), nine treatment-related (pharmacological and non-pharmacological information), and 3 related to the impact of RRMS on the patient's life (quality of life, pregnancy desire, work-related difficulties). In addition, experts also agreed to collect 10 case-mix variables that may affect but cannot be controlled as part of the management of the condition: 4 sociodemographic (age, sex, race, and employment status) and 6 clinical (height, date of diagnosis and first episode, serological status, early symptoms, and number of relapses pre-diagnosis). Conclusion The information provided through the present standard set of outcome variables can improve the management of RRMS and promote patient-centred quality care.This project was supported by Bristol Myers Squibb

International consensus on (ICON) anaphylaxis

ICON: Anaphylaxis provides a unique perspective on the principal evidence-based anaphylaxis guidelines developed and published independently from 2010 through 2014 by four allergy/immunology organizations. These guidelines concur with regard to the clinical features that indicate a likely diagnosis of anaphylaxis -- a life-threatening generalized or systemic allergic or hypersensitivity reaction. They also concur about prompt initial treatment with intramuscular injection of epinephrine (adrenaline) in the mid-outer thigh, positioning the patient supine (semi-reclining if dyspneic or vomiting), calling for help, and when indicated, providing supplemental oxygen, intravenous fluid resuscitation and cardiopulmonary resuscitation, along with concomitant monitoring of vital signs and oxygenation. Additionally, they concur that H1-antihistamines, H2-antihistamines, and glucocorticoids are not initial medications of choice. For self-management of patients at risk of anaphylaxis in community settings, they recommend carrying epinephrine auto-injectors and personalized emergency action plans, as well as follow-up with a physician (ideally an allergy/immunology specialist) to help prevent anaphylaxis recurrences. ICON: Anaphylaxis describes unmet needs in anaphylaxis, noting that although epinephrine in 1 mg/mL ampules is available worldwide, other essentials, including supplemental oxygen, intravenous fluid resuscitation, and epinephrine auto-injectors are not universally available. ICON: Anaphylaxis proposes a comprehensive international research agenda that calls for additional prospective studies of anaphylaxis epidemiology, patient risk factors and co-factors, triggers, clinical criteria for diagnosis, randomized controlled trials of therapeutic interventions, and measures to prevent anaphylaxis recurrences. It also calls for facilitation of global collaborations in anaphylaxis research. In addition to confirming the alignment of major anaphylaxis guidelines, ICON: Anaphylaxis adds value by including summary tables and citing 130 key references. It is published as an information resource about anaphylaxis for worldwide use by healthcare professionals, academics, policy-makers, patients, caregivers, and the public

Prospective study of urinary tract infection surveillance after kidney transplantation

<p>Abstract</p> <p>Background</p> <p>Urinary tract infection (UTI) remains one of the main complications after kidney transplantation and it has serious consequences.</p> <p>Methods</p> <p>Fifty-two patients with kidney transplantation were evaluated for UTI at 3-145 days (mean 40.0 days) after surgery.. Forty-two received a graft from a live donor and 10 from a deceased donor. There were 22 female and 30 male patients, aged 11-47 years. Microscopic examinations, leukocyte esterase stick, and urinary culture were performed every third day and weekly after hospitalization. A positive culture was consider when patients presented bacterial counts up to 10⁵ counts.</p> <p>Results</p> <p>UTI developed in 19/52 (37%) patients at 3-75 days (mean 19.5 days after transplantation. Recurrent infection was observed in 7/52 (13.4%) patients at days 17-65. UTI was more frequent in patients who received deceased grafts compared with live grafts (7/10, 70% <it>vs</it>. 12/42, 28%; p < 0.007). Female patients were more susceptible than male (11/22, 50% <it>vs</it>. 8/22, 36.35%; p < 0.042). Five-year survival rate was 94.5% (49/52 patients). Kidney Graft exit update is 47/52 (90.2%), and there were no significant differences between graft rejection and UTI (p = 0.2518). Isolated bacteria were <it>Escherichia coli </it>(31.5%), <it>Candida albicans </it>(21.0%) and <it>Enterococcus </it>spp. (10.5%), followed by <it>Pseudomonas aeruginosa, Klebsiella pneumoniae, Morganella </it><it>morganii, Enterobacter cloacae </it>and <it>Micrococcus </it>spp. Secondary infections were produced by (7/19, 36.8%). <it>Enterococcus </it>spp. (57%), <it>E. coli </it>(28%) and <it>Micrococcus </it>spp. (14.2%). Antibiotic resistance was 22% for ciprofloxacin and 33% for ampicillin. Therapeutic alternatives were aztreonam, trimethoprim-sulfamethoxazole, netilmicin and fosfomycin.</p> <p>Conclusions</p> <p>Surveillance of UTI for the first 3 months is a good option for improving quality of life of kidney transplantation patients and the exit of graft function especially for female patients and those receiving deceased grafts. Antibiograms provided a good therapeutic alternative to patients who presented with UTIs after receiving a kidney allograft.</p