A remark on Bishop's multivalued projections

We present a proof of an extension theorem for holomorphic functions based on holomorphic multivalued projections

THE ROLE OF SELECTIVE ESTROGEN RECEPTOR MODULATORS IN THE TREATMENT OF SCHIZOPHRENIA

Background: Gender differences in schizophrenia have been recognized for a long time and it has been widely accepted that sex steroid hormones, especially estradiol, are strongly attributed to this fact. Two hypotheses regarding estradiol action in psychoses gained special research attention – the estrogen protection hypothesis and hypoestrogenism hypothesis. A growing number of studies have shown benefits in augmenting antipsychotic treatment with estrogens or selective estrogen receptor modulators (SERM). Methods: This review is focused on the role of selective estrogen receptor modulators in the treatment of schizophrenic patients. In order to achieve this result PubMed was searched using the following terms: schizophrenia, raloxifene, humans. We reviewed only randomized, placebo-controlled studies. Results: Raloxifene, a selective estrogen receptor modulator was identified as useful to improve negative, positive, and general psychopathological symptoms, and also cognitive functions. All reviewed studies indicated improvement in at least one studied domain. Augmentation with raloxifene was found to be a beneficial treatment strategy for chronic schizophrenia both in female and male patients, however potential side effects (a small increase in the risk of venous thromboembolism and endometrial cancer) should be carefully considered. Conclusions: SERMs could be an effective augmentation strategy in the treatment of both men women with schizophrenia, although further research efforts are needed to study potential long-term side effects

ASSOCIATION BETWEEN DEPRESSION AND HEMODIALYSIS IN PATIENTS WITH CHRONIC KIDNEY DISEASE

Depression is the most common and serious psychiatric disorder that affects patients with chronic kidney disease and end-stage renal disease, and, has a significant impact on their quality of life. The aim of this study was to investigate and compare prevalence rates of depression among hemodialyzed patients, and non-dialyzed patients with a glomerular filtration rate <30 ml/min/1.73m2 receiving conservative treatment or following kidney transplantation. A total of 50 hemodialyzed and 50 non-dialyzed patients with stage 4/5 of CKD was assessed using the following questionnaires: Hamilton Anxiety Rating Scale (HAM-A), Hamilton Depression Rating Scale (HAM-D), The Satisfaction with Life Scale (SWLS), The Acceptance of Illness Scale (AIS), and The Life Orientation Test-Revised (LOT-R). The use of steroids and immunosuppressant drugs was also investigated. Symptoms of depression and anxiety were present in both groups, however the proportion of persons with mild or severe depression was higher among dialyzed patients. The AIS, LOT-R and SWLS scores were very similar in both the groups. The patients using steroids and/or immunosuppressant drugs were more prone to develop mild or severe depression according to the HAM-D scores. The results indicated a high prevalence of depression and anxiety among patients with CKD. Furthermore, the fraction of patients with depression is greater among hemodialyzed patients. This indicates the importance of monitoring the mental state of the patients as well as the necessity of providing timely psychological care for patients with CKD

THE PREVALENCE OF SEASONAL AFFECTIVE DISORDER AMONG THE BLIND AND PATIENTS WITH SERIOUS VISUAL IMPAIRMENT

Background: Seasonal affective disorder (SAD) is an interesting disorder in which depression should occur at a particular time of a year, each year and it should disappear at a specific time of the year. While the prevalence of SAD among generally healthy individuals is well known, the information about the prevalence of this disorder among the blind and visually impaired patients is very limited. The aim of the study was to investigate the prevalence of SAD among the blind and people with serious visual impairment in polish population. Subjects and methods: 250 blind or seriously visually impaired individuals and 258 healthy controls were assessed with the usage of Seasonal Pattern Assessment Questionnaire (SPAQ). In research group survey was conducted with the Computer Assisted Telephone Interview (CATI) technique. In control group the questionnaire was distributed via Internet. The results were analysed with the usage statistical package - Statistica 13.1. Results: The results revealed that among people suffering from SAD there is statistically significant difference in SPAQ scores between completely blind and seriously visually impaired people. The study shows that is the control group age is negatively correlated with score in SPAQ score, while in the study group age is positively correlated with SPAQ score. The data show that there is a difference in occurrence of SAD between men and women. Conclusion: The study has shown a significant difference in occurrence of SAD between study and control groups. What is more the analysis has indicated major difference in the occurrence of SAD between men and women from the study group. Taking into consideration the fact that this is the second analysis of this type in Europe further investigations are needed

THE PREVALENCE OF SEASONAL AFFECTIVE DISORDER AMONG THE BLIND AND PATIENTS WITH SERIOUS VISUAL IMPAIRMENT

Background: Seasonal affective disorder (SAD) is an interesting disorder in which depression should occur at a particular time of a year, each year and it should disappear at a specific time of the year. While the prevalence of SAD among generally healthy individuals is well known, the information about the prevalence of this disorder among the blind and visually impaired patients is very limited. The aim of the study was to investigate the prevalence of SAD among the blind and people with serious visual impairment in polish population. Subjects and methods: 250 blind or seriously visually impaired individuals and 258 healthy controls were assessed with the usage of Seasonal Pattern Assessment Questionnaire (SPAQ). In research group survey was conducted with the Computer Assisted Telephone Interview (CATI) technique. In control group the questionnaire was distributed via Internet. The results were analysed with the usage statistical package - Statistica 13.1. Results: The results revealed that among people suffering from SAD there is statistically significant difference in SPAQ scores between completely blind and seriously visually impaired people. The study shows that is the control group age is negatively correlated with score in SPAQ score, while in the study group age is positively correlated with SPAQ score. The data show that there is a difference in occurrence of SAD between men and women. Conclusion: The study has shown a significant difference in occurrence of SAD between study and control groups. What is more the analysis has indicated major difference in the occurrence of SAD between men and women from the study group. Taking into consideration the fact that this is the second analysis of this type in Europe further investigations are needed

Antitumor effect of anti-vascular therapy with STING agonist depends on the tumor microenvironment context

IntroductionTargeting tumor vasculature is an efficient weapon to fight against cancer; however, activation of alternative pathways to rebuild the disrupted vasculature leads to rapid tumor regrowth. Immunotherapy that exploits host immune cells to elicit and sustain potent antitumor response has emerged as one of the most promising tools for cancer treatment, yet many treatments fail due to developed resistance mechanisms. Therefore, our aim was to examine whether combination of immunotherapy and anti-vascular treatment will succeed in poorly immunogenic, difficult-to-treat melanoma and triple-negative breast tumor models.MethodsOur study was performed on B16-F10 melanoma and 4T1 breast tumor murine models. Mice were treated with the stimulator of interferon genes (STING) pathway agonist (cGAMP) and vascular disrupting agent combretastatin A4 phosphate (CA4P). Tumor growth was monitored. The tumor microenvironment (TME) was comprehensively investigated using multiplex immunofluorescence and flow cytometry. We also examined if such designed therapy sensitizes investigated tumor models to an immune checkpoint inhibitor (anti-PD-1).ResultsThe use of STING agonist cGAMP as monotherapy was insufficient to effectively inhibit tumor growth due to low levels of STING protein in 4T1 tumors. However, when additionally combined with an anti-vascular agent, a significant therapeutic effect was obtained. In this model, the obtained effect was related to the TME polarization and the stimulation of the innate immune response, especially activation of NK cells. Combination therapy was unable to activate CD8+ T cells. Due to the lack of PD-1 upregulation, no improved therapeutic effect was observed when additionally combined with the anti-PD-1 inhibitor. In B16-F10 tumors, highly abundant in STING protein, cGAMP as monotherapy was sufficient to induce potent antitumor response. In this model, the therapeutic effect was due to the infiltration of the TME with activated NK cells. cGAMP also caused the infiltration of CD8+PD-1+ T cells into the TME; hence, additional benefits of using the PD-1 inhibitor were observed.ConclusionThe study provides preclinical evidence for a great influence of the TME on the outcome of applied therapy, including immune cell contribution and ICI responsiveness. We pointed the need of careful TME screening prior to antitumor treatments to achieve satisfactory results

Meeting reports: Research on Coupled Human and Natural Systems (CHANS): Approach, Challenges, and Strategies

Understanding the complexity of human–nature interactions is central to the quest for both human well-being and global sustainability. To build an understanding of these interactions, scientists, planners, resource managers, policymakers, and communities increasingly are collaborating across wide-ranging disciplines and knowledge domains. Scientists and others are generating new integrated knowledge on top of their requisite specialized knowledge to understand complex systems in order to solve pressing environmental and social problems (e.g., Carpenter et al. 2009). One approach to this sort of integration, bringing together detailed knowledge of various disciplines (e.g., social, economic, biological, and geophysical), has become known as the study of Coupled Human and Natural Systems, or CHANS (Liu et al. 2007a, b). In 2007 a formal standing program in Dynamics of Coupled Natural and Human Systems was created by the U.S. National Science Foundation. Recently, the program supported the launch of an International Network of Research on Coupled Human and Natural Systems (CHANS-Net.org). A major kick-off event of the network was a symposium on Complexity in Human–Nature Interactions across Landscapes, which brought together leading CHANS scientists at the 2009 meeting of the U.S. Regional Association of the International Association for Landscape Ecology in Snowbird, Utah. The symposium highlighted original and innovative research emphasizing reciprocal interactions between human and natural systems at multiple spatial, temporal, and organizational scales. The presentations can be found at ‹http://chans- net.org/Symposium_2009.aspx›. The symposium was accompanied by a workshop on Challenges and Opportunities in CHANS Research. This article provides an overview of the CHANS approach, outlines the primary challenges facing the CHANS research community, and discusses potential strategies to meet these challenges, based upon the presentations and discussions among participants at the Snowbird meeting

Raphe-mediated signals control the hippocampal response to SRI antidepressants via miR-16

Serotonin reuptake inhibitor (SRI) antidepressants such as fluoxetine (Prozac), promote hippocampal neurogenesis. They also increase the levels of the bcl-2 protein, whose overexpression in transgenic mice enhances adult hippocampal neurogenesis. However, the mechanisms underlying SRI-mediated neurogenesis are unclear. Recently, we identified the microRNA miR-16 as an important effector of SRI antidepressant action in serotonergic raphe and noradrenergic locus coeruleus (LC). We show here that miR-16 mediates adult neurogenesis in the mouse hippocampus. Fluoxetine, acting on serotonergic raphe neurons, decreases the amount of miR-16 in the hippocampus, which in turn increases the levels of the serotonin transporter (SERT), the target of SRI, and that of bcl-2 and the number of cells positive for Doublecortin, a marker of neuronal maturation. Neutralization of miR-16 in the hippocampus further exerts an antidepressant-like effect in behavioral tests. The fluoxetine-induced hippocampal response is relayed, in part, by the neurotrophic factor S100β, secreted by raphe and acting via the LC. Fluoxetine-exposed serotonergic neurons also secrete brain-derived neurotrophic factor, Wnt2 and 15-Deoxy-delta12,14-prostaglandin J2. These molecules are unable to mimic on their own the action of fluoxetine and we show that they act synergistically to regulate miR-16 at the hippocampus. Of note, these signaling molecules are increased in the cerebrospinal fluid of depressed patients upon fluoxetine treatment. Thus, our results demonstrate that miR-16 mediates the action of fluoxetine by acting as a micromanager of hippocampal neurogenesis. They further clarify the signals and the pathways involved in the hippocampal response to fluoxetine, which may help refine therapeutic strategies to alleviate depressive disorders

Dysregulation of chemo-cytokine production in schizophrenic patients versus healthy controls

<p>Abstract</p> <p>Background</p> <p>The exact cause of schizophrenia is not known, although several aetiological theories have been proposed for the disease, including developmental or neurodegenerative processes, neurotransmitter abnormalities, viral infection and immune dysfunction or autoimmune mechanisms. Growing evidence suggests that specific cytokines and chemokines play a role in signalling the brain to produce neurochemical, neuroendocrine, neuroimmune and behavioural changes. A relationship between inflammation and schizophrenia was supported by abnormal cytokines production, abnormal concentrations of cytokines and cytokine receptors in the blood and cerebrospinal fluid in schizophrenia. Since the neuropathology of schizophrenia has recently been reported to be closely associated with microglial activation we aimed to determined whether spontaneous or LPS-induced peripheral blood mononuclear cell chemokines and cytokines production is dysregulated in schizophrenic patients compared to healthy subjects. We enrolled 51 untreated first-episode schizophrenics (SC) and 40 healthy subjects (HC) and the levels of MCP-1, MIP-1α, IL-8, IL-18, IFN-γ and RANTES were determined by Elisa method in cell-free supernatants of PBMC cultures.</p> <p>Results</p> <p>In the simultaneous quantification we found significantly higher levels of constitutively and LPS-induced MCP-1, MIP-1α, IL-8 and IL-18, and lower RANTES and IFNγ levels released by PBMC of SC patients compared with HC. In ten SC patients receiving therapy with risperidone, olanzapine or clozapine basal and LPS-induced production of RANTES and IL-18 was increased, while both basal and LPS-induced MCP-1 production was decreased. No statistically significant differences were detected in serum levels after therapy.</p> <p>Conclusion</p> <p>The observation that in schizophrenic patients the PBMC production of selected chemo-cytokines is dysregulated reinforces the hypothesis that the peripheral cyto-chemokine network is involved in the pathophysiology of schizophrenia. These preliminary, but promising data are supportive of the application of wider profiling approaches to the identification of biomarker as diagnostic tools for the analysis of psychiatric diseases.</p