The epidemiology of suicide behaviors among the countries of the eastern Mediterranean region of WHO: A systematic review

This systematic review aimed to help better to understand the epidemiology of suicidal behaviors among Eastern Mediterranean Region (EMR) countries. The PubMed, EMR medex, Scopus, PsychInfo, ISI, and IMEMR were searched with no language limitation for papers on the epidemiology of suicidal behaviors in the general population, published up to August 2013. A total of 13 articles were reviewed. The incidence (per 100.000) of committed suicide ranged from 0.55 to 5.4. The lifelong prevalence of attempted suicide, suicidal plan and thoughts were 0.72-4.2, 6.2-6.7, and 2.9-14.1, respectively. The figures for suicide are higher than those officially reported. Suicide behaviors� statistics is susceptible to underestimation presumably due to the socio-cultural, religious and legal barriers, not to mention the lack of well-organized registries and methodologically sound community-based surveys. © 2015 Tehran University of Medical Sciences. All rights reserved

Povezanost između radiografskih nalaza, magnetske rezonancije i histopatoloških nalaza kod pokusne rupture prednje križne sveze u kunića.

Experimental osteoarthritis (OA) was induced in the knee joints of rabbits and the trend of changes were compared by radiography, Magnetic Resonance Imaging (MRI) and histopathology. Twenty rabbits were randomly divided into two equal groups based on short (30 days) and long-term (180 days) follow ups. In half of the animals in each group (n = 5) OA was induced by sectioning the cranial cruciate ligament and in the other half, only arthrotomy was performed as a sham operation. Radiography and MRI were carried out on days 0 and 30 in the group of short term studies, and on days 0, 90 and 180 in the other group. Histopathological examinations were performed on day 30 in the short-term group after the animals had been sacrificed and in the other group on day 180. The slope of changes over the course of the study between all 3 methods and the grade of changes, were both highest in histopathology, and then in MRI and radiology respectively. The slope of changes was 0.01 for histopathology, 0.009 for MRI and 0.004 for radiology. The ratios of slopes, when compare to each other, were as follows: His./MRI = 1.1, His./Rad. = 2.5, MRI/Rad. = 2.2. Comparison of MRI with radiology revealed that radiology would not show signs of OA when the MRI grade is less than a grade of 0.27. Comparing both imaging techniques with histopathology showed that whenever the histopathological grade was below 0.22, radiology would not show signs of OA involvement, while MRI was capable of showing signs of OA involvement whenever it was more than 0.018 on histopathological grade.Nakon što je u kunića pokusno izazvan osteoartritis koljenog zgloba, trend promjena promatran je pomoću radiografije, magnetske rezonancije (MRI) i patohistoloških nalaza. Dvadeset kunića bilo je metodom slučajnog odabira podijeljeno u dvije jednake skupine od kojih je jedna promatrana tijekom kratkotrajnog (30 dana), a druga tijekom dugotrajnog (180 dana) razdoblja. U polovice životinja iz svake skupine (n = 5) osteoartroza je bila uzrokovana sekcijom prednje križne sveze, a kod druge polovice primijenjena je samo artrotomija kao lažna operacija. Radiografija i magnetska rezonancija obavljene su 0-ti i 30. dan tijekom kratkotrajnog promatranja te 0-ti, 90. i 180. dan kod dugotrajnog promatranja. Histopatološke pretrage obavljene su 30. dan kod kratkotrajnog praćenja nakon što su životinje bile usmrćene, a kod dugotrajnog 180. dan. Slabljenje promjena tijekom promatranja svima trima metodama kao i stupanj promjena pokazali su se najvećima kod histopatoloških nalaza, zatim kod magnetske rezonancije te nakon toga kod radioloških snimki. Slabljenje promjena bilo je 0,01 za histopatološke nalaze, 0,009 za magnetsku rezonanciju i 0,004 za radiološke snimke. Kad se uzmu u obzir međusobni odnosi slabljenja su bila sljedeća: His./MRI = 1,1, His./Rad. = 2,5, MRI/Rad. = 2,2. Usporedba magnetske rezonancije i radiologije potvrdila je da radiologija neće pokazati znakove osteoartritisa kada je stupanj magnetske rezonance niži od 0,27. Usporedbom obje tehnike snimanja s histopatološkim nalazima utvrđeno je da radiologija neće pokazati znakove osteoartritisa kad je stupanj histopatoloških nalaza ispod 0,22. Primjenom magnentske rezonancije moguće je utvrditi znakove osteoartritisa svaki put kada je njezin stupanj veći od 0,018 u odnosu na stupanj histopatoloških nalaza

Disruption of Neuronal Autophagy by Infected Microglia Results in Neurodegeneration

There is compelling evidence to support the idea that autophagy has a protective function in neurons and its disruption results in neurodegenerative disorders. Neuronal damage is well-documented in the brains of HIV-infected individuals, and evidence of inflammation, oxidative stress, damage to synaptic and dendritic structures, and neuronal loss are present in the brains of those with HIV-associated dementia. We investigated the role of autophagy in microglia-induced neurotoxicity in primary rodent neurons, primate and human models. We demonstrate here that products of simian immunodeficiency virus (SIV)-infected microglia inhibit neuronal autophagy, resulting in decreased neuronal survival. Quantitative analysis of autophagy vacuole numbers in rat primary neurons revealed a striking loss from the processes. Assessment of multiple biochemical markers of autophagic activity confirmed the inhibition of autophagy in neurons. Importantly, autophagy could be induced in neurons through rapamycin treatment, and such treatment conferred significant protection to neurons. Two major mediators of HIV-induced neurotoxicity, tumor necrosis factor-α and glutamate, had similar effects on reducing autophagy in neurons. The mRNA level of p62 was increased in the brain in SIV encephalitis and as well as in brains from individuals with HIV dementia, and abnormal neuronal p62 dot structures immunoreactivity was present and had a similar pattern with abnormal ubiquitinylated proteins. Taken together, these results identify that induction of deficits in autophagy is a significant mechanism for neurodegenerative processes that arise from glial, as opposed to neuronal, sources, and that the maintenance of autophagy may have a pivotal role in neuroprotection in the setting of HIV infection

HIV-associated neurocognitive disorders in sub-Saharan Africa: a pilot study in Cameroon

<p>Abstract</p> <p>Background</p> <p>The disease burden of human immunodeficiency virus (HIV) - acquired immunodeficiency syndrome (AIDS) is highest in sub-Saharan Africa but there are few studies on the associated neurocognitive disorders in this region. The objectives of this study were to determine whether Western neuropsychological (NP) methods are appropriate for use in Cameroon, and to evaluate cognitive function in a sample of HIV-infected adults.</p> <p>Methods</p> <p>We used a battery of 19 NP measures in a cross-sectional study with 44 HIV+ adults and 44 demographically matched HIV- controls, to explore the validity of these NP measures in Cameroon, and evaluate the effect of viral infection on seven cognitive ability domains.</p> <p>Results</p> <p>In this pilot study, the global mean z-score on the NP battery showed worse overall cognition in the HIV+ individuals. Significantly lower performance was seen in the HIV+ sample on tests of executive function, speed of information processing, working memory, and psychomotor speed. HIV+ participants with AIDS performed worse than those with less advanced HIV disease.</p> <p>Conclusions</p> <p>Similar to findings in Western cohorts, our results in Cameroon suggest that HIV infection, particularly in advanced stages, is associated with worse performance on standardized, Western neurocognitive tests. The tests used here appear to be promising for studying NeuroAIDS in sub-Saharan Africa.</p

HIV-1 Inhibits Autophagy in Bystander Macrophage/Monocytic Cells through Src-Akt and STAT3

Autophagy is a homeostatic mechanism of lysosomal degradation. Defective autophagy has been linked to various disorders such as impaired control of pathogens and neurodegeneration. Autophagy is regulated by a complex array of signaling pathways that act upstream of autophagy proteins. Little is known about the role of altered regulatory signaling in disorders associated with defective autophagy. In particular, it is not known if pathogens inhibit autophagy by modulation of upstream regulatory pathways. Cells infected with HIV-1 blocked rapamycin-induced autophagy and CD40-induced autophagic killing of Toxoplasma gondii in bystander (non-HIV-1 infected) macrophage/monocytic cells. Blockade of autophagy was dependent on Src-Akt and STAT3 triggered by HIV-1 Tat and IL-10. Neutralization of the upstream receptors VEGFR, β-integrin or CXCR4, as well as of HIV-1 Tat or IL-10 restored autophagy in macrophage/monocytic cells exposed to HIV-1-infected cells. Defective autophagic killing of T. gondii was detected in monocyte-derived macrophages from a subset of HIV-1+ patients. This defect was also reverted by neutralization of Tat or IL-10. These studies revealed that a pathogen can impair autophagy in non-infected cells by activating counter-regulatory pathways. The fact that pharmacologic manipulation of cell signaling restored autophagy in cells exposed to HIV-1-infected cells raises the possibility of therapeutic manipulation of cell signaling to restore autophagy in HIV-1 infection

Hepatitis C Virus Core Protein Induces Neuroimmune Activation and Potentiates Human Immunodeficiency Virus-1 Neurotoxicity

BACKGROUND: Hepatitis C virus (HCV) genomes and proteins are present in human brain tissues although the impact of HIV/HCV co-infection on neuropathogenesis remains unclear. Herein, we investigate HCV infectivity and effects on neuronal survival and neuroinflammation in conjunction with HIV infection. METHODOLOGY: Human microglia, astrocyte and neuron cultures were infected with cell culture-derived HCV or exposed to HCV core protein with or without HIV-1 infection or HIV-1 Viral Protein R (Vpr) exposure. Host immune gene expression and cell viability were measured. Patch-clamp studies of human neurons were performed in the presence or absence of HCV core protein. Neurobehavioral performance and neuropathology were examined in HIV-1 Vpr-transgenic mice in which stereotaxic intrastriatal implants of HCV core protein were performed. PRINCIPAL FINDINGS: HCV-encoded RNA as well as HCV core and non-structural 3 (NS3) proteins were detectable in human microglia and astrocytes infected with HCV. HCV core protein exposure induced expression of pro-inflammatory cytokines including interleukin-1β, interleukin-6 and tumor necrosis factor-α in microglia (p<0.05) but not in astrocytes while increased chemokine (e.g. CXCL10 and interleukin-8) expression was observed in both microglia and astrocytes (p<0.05). HCV core protein modulated neuronal membrane currents and reduced both β-III-tubulin and lipidated LC3-II expression (p<0.05). Neurons exposed to supernatants from HCV core-activated microglia exhibited reduced β-III-tubulin expression (p<0.05). HCV core protein neurotoxicity and interleukin-6 induction were potentiated by HIV-1 Vpr protein (p<0.05). HIV-1 Vpr transgenic mice implanted with HCV core protein showed gliosis, reduced neuronal counts together with diminished LC3 immunoreactivity. HCV core-implanted animals displayed neurobehavioral deficits at days 7 and 14 post-implantation (p<0.05). CONCLUSIONS: HCV core protein exposure caused neuronal injury through suppression of neuronal autophagy in addition to neuroimmune activation. The additive neurotoxic effects of HCV- and HIV-encoded proteins highlight extrahepatic mechanisms by which HCV infection worsens the disease course of HIV infection

Guidelines for the use and interpretation of assays for monitoring autophagy (3rd edition)

In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. For example, a key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process versus those that measure fl ux through the autophagy pathway (i.e., the complete process including the amount and rate of cargo sequestered and degraded). In particular, a block in macroautophagy that results in autophagosome accumulation must be differentiated from stimuli that increase autophagic activity, defi ned as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (inmost higher eukaryotes and some protists such as Dictyostelium ) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the fi eld understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. It is worth emphasizing here that lysosomal digestion is a stage of autophagy and evaluating its competence is a crucial part of the evaluation of autophagic flux, or complete autophagy. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. Along these lines, because of the potential for pleiotropic effects due to blocking autophagy through genetic manipulation it is imperative to delete or knock down more than one autophagy-related gene. In addition, some individual Atg proteins, or groups of proteins, are involved in other cellular pathways so not all Atg proteins can be used as a specific marker for an autophagic process. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular autophagy assays, we hope to encourage technical innovation in the field

Genetic Basis of Myocarditis: Myth or Reality?

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