Mental health research priorities in low- and middle-income countries of Africa, Asia, Latin America and the Caribbean.

BACKGROUND: Studies suggest a paucity of and lack of prioritisation in mental health research from low- and middle-income (LAMI) countries. AIMS: To investigate research priorities in mental health among researchers and other stakeholders in LAMI countries. METHOD: We used a two-stage design that included identification, through literature searches and snowball technique, of researchers and stakeholders in 114 countries of Africa, Asia, Latin America and the Caribbean; and a mail survey on priorities in research. RESULTS: The study identified broad agreement between researchers and stakeholders and across regions regarding research priorities. Epidemiology (burden and risk factors), health systems and social science ranked highest for type of research. Depression/anxiety, substance use disorders and psychoses; and children and adolescents, women, and people exposed to violence/trauma were prioritised among the disorders and population groups respectively. Important criteria for prioritising research were burden of disease, social justice, and availability of funds. Stakeholder groups differed in the importance they gave to the personal interest of researchers as a criterion for prioritising research. Researchers' and stakeholders' priorities were consistent with burden of disease estimates, however suicide was underprioritised compared with its burden. Researchers' and stakeholders' priorities were also largely congruent with the researchers' projects. CONCLUSIONS: The results of this first ever conducted survey of researchers and stakeholders regarding research priorities in mental health suggest that it should be possible to develop consensus at regional and international levels regarding the research agenda that is necessary to support health system objectives in LAMI countries.

Immunohistochemical and biochemical assay of versican in human sound predentine/dentine matrix.

Aim of this study was to investigate the distribution of versican proteoglycan within the human dentine organic matrix by means of a correlative immunohistochemical analysis with field emission in-lens scanning electron microscope (FEI-SEM), transmission electron microscope (TEM), fluorescence microscope (FM) and biochemical assay. Specimens containing dentine and predentine were obtained from non carious human teeth and divided in three groups: 1) FEI-SEM group: sections were exposed to a pre-embedding immunohistochemical procedure; 2) TEM group: specimens were fixed, demineralised, embedded and submitted to a post-embedding immunohistochemical procedure; 3) FM group: sections mineralised and submitted to a pre-embedding immunohistochemical procedure with fluorescence labelling. Specimens were exposed to two different antibodies to assay distribution of versican fragments and whole versican molecule.Western Blotting analysis of dentine and pulp extracts was also performed. The correlative FEI-SEM,TEM and FM analysis revealed positive immunoreaction for versican fragments both in predentine and dentine, while few gold particles identifying the whole versican molecule were found in predentine only under TEM. No labelling of versican whole molecule was detected by FEI-SEM and FM analysis. The immunoblotting analysis confirmed the morphological findings. This study suggests that in fully developed human teeth versican fragments are significant constituents of the human dentine and predentine organic matrix, while versican whole molecule can be visualised in scarce amount within predentine only. The role of versican fragments within human dentine organic matrix should be further elucidated.

Influence of luting material filler content on post cementation.

Luting of fiber posts to intra-radicular dentin represents the worst-case scenario in terms of control of polymerization shrinkage. This study tested the hypothesis that filler content of resin cements does not influence luting of fiber posts to intra-radicular dentin, by assaying polymerization stress, push-out bond strength, and nanoleakage expression. The polymerization stress of experimental cements containing 10%, 30%, 50%, or 70% in filler content was investigated. Post spaces were prepared in endodontically treated teeth, and fiber posts were cemented with the experimental cements. A push-out test was performed, and interfacial nanoleakage expression was analyzed. Results showed that luting cements with higher filler content were related to increased polymerization stress (p < 0.05), decreased push-out bond strength (p < 0.05), and increased interfacial nanoleakage expression (p < 0.05). Conversely, lower-stress luting materials increased bonding of fiber posts to intra-radicular dentin. Further in vivo studies are needed to investigate the long-term clinical performance of these materials.

Immunohistochemical and biochemical assay of versican in human sound predentine/dentine matrix.

Aim of this study was to investigate the distribution of versican proteoglycan within the human dentine organic matrix by means of a correlative immunohistochemical analysis with field emission in-lens scanning electron microscope (FEI-SEM), transmission electron microscope (TEM), fluorescence microscope (FM) and biochemical assay. Specimens containing dentine and predentine were obtained from non carious human teeth and divided in three groups: 1) FEI-SEM group: sections were exposed to a pre-embedding immunohistochemical procedure; 2) TEM group: specimens were fixed, demineralised, embedded and submitted to a post-embedding immunohistochemical procedure; 3) FM group: sections mineralised and submitted to a pre-embedding immunohistochemical procedure with fluorescence labelling. Specimens were exposed to two different antibodies to assay distribution of versican fragments and whole versican molecule. Western Blotting analysis of dentine and pulp extracts was also performed. The correlative FEI-SEM,TEM and FM analysis revealed positive immunoreaction for versican fragments both in predentine and dentine, while few gold particles identifying the whole versican molecule were found in predentine only under TEM. No labelling of versican whole molecule was detected by FEI-SEM and FM analysis. The immunoblotting analysis confirmed the morphological findings. This study suggests that in fully developed human teeth versican fragments are significant constituents of the human dentine and predentine organic matrix, while versican whole molecule can be visualised in scarce amount within predentine only. The role of versican fragments within human dentine organic matrix should be further elucidated.

Challenges to reduce the '10/90 gap': mental health research in Latin American and Caribbean countries.

OBJECTIVE: To analyze the status of mental health research in 30 Latin American and Caribbean countries (LAC). METHOD: Medline and PsycInfo databases were searched to identify the LAC authors. Their publications were classified according to the topic, type of research and target population studied. Scientific indicators of these countries were assessed in other two different databases: Essential Scientific Information and Atlas of Science Project, both from Institute for Scientific Information. RESULTS: Indexed-publications were concentrated in six countries: Argentina, Brazil, Chile, Colombia, Mexico and Venezuela. Most studies dealt with the burdensome mental disorders but neglected important topics such as violence and other mental health priorities. CONCLUSION: Mental health research is mostly concentrated in a few LAC countries, but these countries would contribute to reduce the research gap, if they provide research training to their neighbors and engage in bi- or multi-lateral research collaboration on common region priorities.

The legal and ethical frameworkgoverning Body Donation in Europe - Areview of current practice andrecommendations for good practice

Discussions at the inaugural meeting of aTrans-European Pedagogic Research Group forAnatomical Sciences highlighted the fact thatthere exist considerable variations in the legaland ethical frameworks throughout Europeconcerning body bequests for anatomicalexamination. Such differences appear to reflectcultural and religious variations as well as differentlegal and constitutional frameworks. Forexample, there are different views concerningthe “ownership” of cadavers and concerningthe need (perceived by different societies andnational politicians) for legislation specificallyrelated to anatomical dissection. Furthermore,there are different views concerning the acceptabilityof using unclaimed bodies that have notgiven informed consent. Given that in Europe (AU)

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The nuclear envelope, human genetic diseases and ageing.

Here we present an overview of the experimental evidence and of the conceptual basis for the involvement of lamins and nuclear envelope proteins in a group of genetic diseases collectively referred to as laminopathies. Some of these diseases affect a specific tissue (skeletal and/or cardiac muscles, subcutaneous fat, peripheral nerves), while others affect a variety of tissues; this suggests that the pathogenic mechanism of laminopathies could reside in the alteration of basic mechanisms affecting gene expression. On the other hand, a common feature of cells from laminopathic patients is represented by nuclear shape alterations and heterochromatin rearrangements. The definition of the role of lamins in the fine regulation of heterochromatin organization may help understanding not only the pathogenic mechanism of laminopathies but also the molecular basis of cell differentiation and ageng.

Immunohistochemical identification of decorin and biglycan in human dentin: a correlative field emission scanning electron microscopy/transmission electron microscopy study.

Decorin and biglycan, two small leucine-rich proteoglycans, have been proposed to play important roles in matrix-mediated formation of mineralized tissues, and their three-dimensional arrangement in human dentin is still not completely understood. The aim of this study was to immunohistochemically analyze the distribution of decorin and biglycan in human predentin/dentin organic matrix under a high-resolution field emission in-lens scanning electron microscope (FEI-SEM) and a transmission electron microscope (TEM). Tooth dentin specimens were submitted to either a preembedding or a postembedding immunolabeling technique using primary antibodies antidecorin and antibiglycan and gold-conjugated secondary antibodies. Correlative FEI-SEM/TEM observations showed that the two antibodies yielded a similar labeling pattern over the processes of odontoblasts and the predentin. Decorin and biglycan were mainly associated with the collagen fibers within the predentin layer, revealing a moderate immunoreaction that was significantly higher compared to the one observed on dentin. Thus, a generally weak labeling for decorin was found in dentin, which, however, was significantly higher on odontoblast processes within dentinal tubules than in intertubular dentin. On the other hand, biglycan immunolocalization on dentin revealed few gold particles rather uniformly distributed, without showing significant differences between tubular and intertubular regions. In conclusion, this study reveals distinct distribution patterns of decorin and biglycan and their relation with collagen. Decorin's and biglycan's precise roles within prematrix and mineralized matrix in human teeth should be further clarified.

Effects of HEMA on type I collagen protein in human gingival fibroblasts.

The cytotoxicity of dental composites has been attributed to the release of residual monomers from polymerized adhesive systems due to degradation processes or the incomplete polymerization of materials. 2-Hydroxyethyl methacrylate (HEMA) is one of the major components released from dental adhesives. Cytotoxic effects due to high concentrations of HEMA have already been investigated, but the influence of minor toxic concentrations on specific proteins such as type I collagen has not been studied in depth. The objective of this project was to study the effect of minor toxic concentrations of HEMA on human gingival fibroblasts (HGFs), investigating modification in cell morphology, cell viability, and the influence on type I collagen protein. Primary lines of human gingival fibroblasts were exposed to 3 mmol/L HEMA for different periods of time (24 h, 72 h, 96 h). The cell vitality was determined by MTT assay, and high-resolution scanning electron microscopy analysis was performed to evaluate differences in cell morphology before and after treatment. The presence and localization of type I collagen was determined by immunofluorescence in HGFs treated with HEMA for the same period of time. The vitality of the cells decreased after 72 h of exposure. The HGFs grown in monolayer and observed by field emission in-lens scanning electron microscopy demonstrated a preserved surface morphology after 24 h of treatment, while they showed an altered morphology after 96 h of treatment. Immunofluorescence demonstrated a reduction of type I collagen due to HEMA exposure after 96 h. From these results, we conclude that low concentrations of HEMA can significantly alter the morphology of human gingival fibroblasts and interfere with the presence of type I collagen protein.

Zymographic analysis and characterization of MMP-2 and -9 forms in human sound dentin.

The role and function of dentin matrix metalloproteinases (MMPs) are not well-understood, but they may play a key role in dentinal caries and the degradation of resin-bonded dentin matrices. To test the null hypothesis that MMP-9 is not found in dentin matrix, we used gelatin zymography to extract and isolate all molecular forms of gelatinolytic MMPs in demineralized mature sound dentin powder obtained from extracted human molars, characterizing and identifying the enzymes by Western blotting. Gelatinolytic MMPs were detected in extracts of demineralized dentin matrix and identified as MMP-2 and MMP-9. Acidic extracts (pH 2.3) yielded 3-8 times more MMP activity than did EDTA (pH 7.4). Their activation may contribute to dentin matrix degradation, which occurs during caries progression and following resin bonding. Inhibition of MMP-2 and -9 proteolytic activity may slow caries progression and increase the durability of resin-dentin bonds.

Electric-current-assisted application of self-etch adhesives to dentin.

The use of electric current during the application of etch-and-rinse adhesive systems has been recently claimed to increase bonding of etch-and-rinse adhesives by enhancing substrate impregnation. The null hypothesis tested in this study was that electrically assisted application has no effect on bond strength of self-etching bonding systems. Three self-etch adhesives (Protect-Bond, Xeno III, and Prompt L-Pop) were applied with the aid of an electric signal-generating device (ElectroBond) and tested vs. controls prepared with the same disposable sponges but without electric current. Specimens bonded under the influence of electric current exhibited increased microtensile bond strength compared with the controls (p<0.05). High-resolution SEM analysis showed that bonding under the influence of electricity reduced interfacial nanoleakage. It is speculated that resin infiltration may be improved by the attraction of polar monomers by an electric current or by modification of the dentin surface charges, resulting in better water substitution or evaporation.

High resolution morphological analysis of in situ human chromosomes.

The purpose of this study was to analyze the inner structure of chromosomes in cells arrested, fixed and cryosectioned in metaphase. The chromosomes in metaphase maps prepared using standard cytogenetic protocols, are usually covered by cellular debris, which obscures the structural details on the surface and limits analysis by techniques when using nanometric resolution. By using cryosectioning, the debris is removed and it is possible to analyze the internal structure of the chromosomes. We described the ultrastructure of chromosome sections fixed with either acetic acid, methanol or glutaraldehyde, evaluating the effect and the influence of the fixative on the morphology. Furthermore, we subjected those cells previously fixed with glutaraldehyde to osmic maceration in order to better visualize the intracellular structure. All samples were examined with a Field Emission In Lens Scanning Electron Microscope (FEISEM), which allows high-resolution analysis of biological samples without any metal coating. The results showed a package morphology in samples fixed with glutaraldehyde, mainly due to the high capacity of the fixative to strongly crosslink the proteins. In contrast, the fibrillar structure seen in cryosections fixed with acetic acid/methanol is due to the propensity of the fixatives to extract and remove proteins. We propose that in situ chromosomes fixed with glutaraldehyde and then osmicated are a good model for studying the inner structure of chromosomes by using high resolution scanning electron microscopy.

Significance of nuclear phospholipase C signaling through type 1 IGF receptor.

The existence of a nuclear polyphosphoinositol metabolism independent from that at the plasma membrane is now widely recognized. Specific changes in the nuclear phosphatidylinositol (Ptdlns) metabolism have been implicated in cell growth, differentiation, and neoplastic transformation. Here we shall review the main features of nuclear inositol lipid signaling through type I IGF receptor, focusing the attention on the role of inositide-specific phospholipase C (PI-PLC) beta1 in cell proliferation and differentiation, given its peculiar localization in the nuclear compartment.

Síntomas obsesivo-compulsivos en esquizofrenia durante el tratamiento con clozapine y antipsicóticos clásicos / Obsessive-compulsive symptoms in schizophrenia durins treatment with clozapine and classic antipsychotic drugs

Introducción. Se trata de comparar la prevalencia de síntomas obsesivo-compulsivos en pacientes con esquizofrenia que reciben tratamiento con clozapina con la de los que reciben antipsicóticos clásicos. Métodos. Se evaluaron pacientes ambulatorios con esquizofrenia en tratamiento con clozapina (n=56) o con antipsicóticos clásicos (n=54) en el Instituto Especializado en Salud Mental Honorio Delgado-Hideyo Noguchi (Perú) para determinar la presencia de síntomas obsesivo-compulsivos a través del Módulo de Trastorno Obsesivo Compulsivo de la Entrevista clínica Estructurada para el DSM-IV y la Lista de Chequeo de Síntomas Obsesivo Compulsivos de Yale-Brown. Resultados: El 46,4% de los pacientes en tratamiento con dozapina presentaron síntomas obsesivo-compulsivos, mientras que esto ocurrió en el 20,4% de los pacientes en tratamiento con antipsicóticos clásicos (p=0,005). Además 21,4% de los pacientes que recibían clozapina y 13% de los tratados con antipsicóticos clásicos presentaron trastorno obsesivo-compulsivo según los criterios del DSM-IV (p=0,31). Conclusión. En pacientes esquizofrénicos el tratamiento con clozapina está asociado con una mayor prevalencia de síntomas obsesivo-compulsivos que la terapia con antipsicóticos clásicos (AU)

Introduction. We compare the prevalence of obsessive-compulsive symptoms in schizophrenic patients in treatment with clozapine and those who receive classic antipsychotic drugs. Method. Outpatients with schizophrenia treated with clozapine (n=56) or classic antipsychotic drugs (n=54) at the Honorio Delgado-Hideyo Noguchi Specialized Institute in Mental Health (Lima-Peru), were evaluated for the presence of obsessive-compulsive symptoms by means of the obsessive-Compulsive Disorder Module of Structured Clinical Interview for DSM-IV and Yale Brown obsessive Compulsive Symptoms Checklist. Result. 46, 4% of patients treated with clozapine presented obsessive-compulsive symptoms while this occurred in 20, 4% of those with classic antipsychotic drugs (p=0.005). In addition, 21,4% of patients with clozapine and 13% of those treated with classic antipsychotics presented obsessive-compulsive disorder according to DSM-IV criteria (p=0.31). Conclusion. In schizophrenic patients, treatment with clozapine is associated with a higher rate of obsessive-compulsive symptoms than treatment with classic antipsychotic drugs (AU)

[Obsessive-compulsive symptoms in schizophrenia during treatment with clozapine and conventional antipsychotic drugs]. / Síntomas obsesivo-compulsivos en esquizofrenia durante el tratamiento con clozapina y antipsicóticos clásicos.

INTRODUCTION: We compare the prevalence of obsessive-compulsive symptoms in schizophrenic patients in treatment with clozapine and those who receive classic antipsychotic drugs. METHOD: Outpatients with schizophrenia treated with clozapine (n = 56) or classic antipsychotic drugs (n = 54) at the Honorio Delgado-Hideyo Noguchi Specialized Institute in Mental Health (Lima-Peru), were evaluated for the presence of obsessive-compulsive symptoms by means of the Obsessive-Compulsive Disorder Module of Structured Clinical Interview for DSM-IV and Yale-Brown Obsessive-Compulsive Symptoms Checklist. RESULTS: 46.4 % of patients treated with clozapine presented obsessive-compulsive symptoms while this occurred in 20.4 % of those with classic antipsychotic drugs (p = 0.005). In addition, 21.4 % of patients with clozapine and 13 % of those treated with classic antipsychotics presented obsessive-compulsive disorder according to DSM-IV criteria (p = 0.31). CONCLUSION: In schizophrenic patients, treatment with clozapine is associated with a higher rate of obsessive-compulsive symptoms than treatment with classic antipsychotic drugs.

Nuclear protein kinase C isoforms and apoptosis.

The process of apoptosis is regulated at multiple levels through phosphorylation by several different protein kinases. The protein kinase C (PKC) family of isozymes have been shown to exert both inhibitory and stimulatory influences on apoptosis. During the apoptotic process phosphorylative events are known to occur also at the nuclear level. Evidence suggests that PKC isoforms play a key role in some steps that lead to nuclear disassembly during the execution phase of apoptosis. This review highlights the recent progress made in determining the roles played by individual PKC nuclear isoforms in the control of apoptosis.

Immunocytochemical analysis of dentin: a double-labeling technique.

Immunocytochemical analysis is a fundamental and selective technique for identifying different molecular components of human dental structure. The hypothesis tested here is that the application of different etching solutions on dentin does not hinder collagen fibrils and proteoglycans from maintaining their immunochemical antigenicity. Human dentin disks were treated with 0.5M of EDTA, citric acid, maleic acid, or phosphoric acid (for 15 or 30 s). A double-immunolabeling technique was performed to identify, simultaneously, collagen fibrils and chondroitin sulfate. The use of different acids resulted in different degrees of labeling. Maleic and citric acids revealed a diffuse and intense labeling for both collagen fibrils and proteoglycans. The use of phosphoric acid on dentin showed a massive coagulation of the proteoglycans (15 s) or very low labeling (30 s). These data clarify that the use of acids on dentin components is able to modify their antigenicity. Moreover, the double-labeling immunocytochemical technique allows understanding of the spatial relationships between the collagen fibrils and proteoglycans of the dentin matrix.

[Sexual behavior at risk for HIV/AIDS and sexually transmitted diseases in male patients with psychotic disorders]. / Conducta sexual de riesgo para VIH/SIDA y enfermedades de transmisión sexual en pacientes varones con trastornos psicóticos.

INTRODUCTION: To assess sexual risk behavior for human immunodeficiency virus (HIV) infection and other sexually transmitted diseases (STD) in males with psychotic disorders and to compare it to that of the patients without these disorders. METHODS: We used a structured interview to collect information regarding sexual risk behavior, knowledge about HIV/AIDS, history of STD and drug use. We included 106 patients with psychotic disorders from a psychiatric institution and 89 control medical out-patients from a general hospital. RESULTS: Among psychotic patients, 70.8% declared that they had had sexual intercourse at some time in their lives and 37.7% during the last year. The psychotic patients had significantly less knowledge about HIV/AIDS than the controls and they had a smaller proportion of stable sexual partners and greater frequency of sexual risk behaviors, such as inconsistent condom use and sexual intercourse with prostitutes. In psychotic patients, inconsistent condom use was associated with more hospitalizations. CONCLUSIONS: Although patients with psychotic disorders have reduced sexual activity, they present greater frequency of sexual risk behaviors that predispose them to acquire HIV infection and other STD.

Conducta sexual de riesgo para VIH/SIDA y enfermedades de transmisión sexual en pacientes varones con trastornos psicóticos / Sexual behavior at risk for HIV/AIDS and sexual transmission diseases in male patients with psychotic disorders

Introducción. Evaluar el comportamiento sexual de riesgo para adquirir infección por el virus de inmunodeficiencia humana (VIH) y otras enfermedades de transmisión sexual (ETS) en pacientes varones con trastornos psicóticos y compararlo con el de pacientes sin dichos trastornos.Métodos. Se utilizó una entrevista estructurada para recolectar información sobre prácticas sexuales de riesgo, conocimientos acerca del VIH/SIDA, antecedentes de ETS y consumo de drogas. Se incluyeron 106 pacientes varones con trastornos psicóticos de una institución psiquiátrica y 89 controles provenientes de consultorios de medicina de un hospital general.Resultados. Entre los pacientes psicóticos, el 70,8 por ciento respondieron haber tenido relaciones sexuales alguna vez en su vida y el 37,7 por ciento en el último año. Los pacientes psicóticos tuvieron significativamente menores conocimientos acerca del VIH/SIDA que los controles, así como una menor proporción de parejas sexuales estables y mayor frecuencia de conductas sexuales de riesgo, tales como uso inconsistente del preservativo y relaciones con trabajadoras sexuales. El empleo inconsistente de preservativos se asoció con mayor número de hospitalizaciones en pacientes psicóticos.Conclusiones. Los pacientes con trastornos psicóticos, a pesar de tener en general una menor actividad sexual, presentan con mayor frecuencia conductas sexuales de riesgo para adquirir infección por VIH y otras ETS (AU)