A psychometric analysis of the Early Trauma Inventory-Short Form in Colombia: CTT and Rasch model.

BACKGROUND: Potential childhood traumatic experiences increase risk for mental and physical health disorders and their precise assessment can help to promote health prevention and promotion strategies for countries with limited data and measurement strategies like Colombia. OBJECTIVE: The goal of the present study is to strengthen evidence for the validity of scores from an adapted version of the Early Trauma Inventory self report-short form (ETI-SF) using Item Response Theory and by assessing factorial invariance across gender and education level. PARTICIPANTS AND SETTING: The study assessed a total of 1909 Colombian participants (66.16 % women, 32.16 % men, 1.68 % other gender; age range 18-72 years old). METHODS: Participants answered the ETI-SF via a web-based sampling strategy. RESULTS: The total scores of the scale showed good reliability coefficients (α = 0.81 and ω = 0.60). A specific analysis for the subscales showed good reliability for the emotional, physical, and sexual trauma subscales (αs and ωs >0.64), while general trauma showed lower than accepted reliability values (α =0.56 and ω = 0.37). Most of the individual items of the scale showed good calibration. The factorial invariance analysis suggests the possibility of some gender and educational differences. CONCLUSIONS: The study confirms particularly high rates of potential childhood traumatic experiences in Colombia and complement data for specific trauma types. Overall, the ETI-SF is confirmed as useful for Colombia, which highlights this scale as a good tool to use for public health assessment. Future research can continue the integration of diverse methods for estimating the quality of the scale.

Mammalian heparanase: gene cloning, expression and function in tumor progression and metastasis.

Heparan sulfate proteoglycans interact with many extracellular matrix constituents, growth factors and enzymes. Degradation of heparan sulfate by endoglycosidic heparanase cleavage affects a variety of biological processes. We have purified a 50-kDa heparanase from human hepatoma and placenta, and now report cloning of the cDNA and gene encoding this enzyme. Expression of the cloned cDNA in insect and mammalian cells yielded 65-kDa and 50-kDa recombinant heparanase proteins. The 50-kDa enzyme represents an N-terminally processed enzyme, at least 100-fold more active than the 65-kDa form. The heparanase mRNA and protein are preferentially expressed in metastatic cell lines and specimens of human breast, colon and liver carcinomas. Low metastatic murine T-lymphoma and melanoma cells transfected with the heparanase cDNA acquired a highly metastatic phenotype in vivo, reflected by a massive liver and lung colonization. This represents the first cloned mammalian heparanase, to our knowledge, and provides direct evidence for its role in tumor metastasis. Cloning of the heparanase gene enables the development of specific molecular probes for early detection and treatment of cancer metastasis and autoimmune disorders.

Tumor suppressor p53 regulates heparanase gene expression.

Mammalian heparanase degrades heparan sulfate, the most prominent polysaccharide of the extracellular matrix. Causal involvement of heparanase in tumor progression is well documented. Little is known, however, about mechanisms that regulate heparanase gene expression. Mutational inactivation of tumor suppressor p53 is the most frequent genetic alteration in human tumors. p53 is a transcription factor that regulates a wide variety of cellular promoters. In this study, we demonstrate that wild-type (wt) p53 binds to heparanase promoter and inhibits its activity, whereas mutant p53 variants failed to exert an inhibitory effect. Moreover, p53-H175R mutant even activated heparanase promoter activity. Elimination or inhibition of p53 in several cell types resulted in a significant increase in heparanase gene expression and enzymatic activity. Trichostatin A abolished the inhibitory effect of wt p53, suggesting the involvement of histone deacetylation in negative regulation of the heparanase promoter. Altogether, our results indicate that the heparanase gene is regulated by p53 under normal conditions, while mutational inactivation of p53 during cancer development leads to induction of heparanase expression, providing a possible explanation for the frequent increase of heparanase levels observed in the course of tumorigenesis.

Aproximaciones evolutivas y psicopatología: Teoría de historia de vida y sistemas psicobiológicos en el trastorno de personalidad límite / Evolutionary approaches and psychopathology: Life history theory and psychobiological systems for borderline personality disorder

La psicología clínica requiere de constantes desarrollos científicos que lleven a una explicación de la complejidad de los trastornos mentales y sus bases causales. Las aproximaciones evolutivas han mostrado ser de particular poder heurístico para esta tarea. Entre ellas, la Teoría de Historia de Vida (THV) incorpora avances teóricos y empíricos novedosos y significativos. No obstante, existe la necesidad de incorporar investigación y aproximaciones evolutivas adicionales de interés. Por lo tanto, en este artículo se propondrá el potencial de integración al ampliar la causalidad evolutiva en conjunción con aproximaciones de sistemas psicobiológicos de conducta. Para esto se utilizará como ejemplo el Trastorno Límite de Personalidad, ampliando su comprensión como una interacción de causas próximas entre los sistemas psicobiológicos de estrés y apego, dentro del marco de causas últimas de THV. Finalmente, se demarcarán aspectos que nutren el campo clínico con implicaciones para la evaluación y los dominios de intervención.(AU)

Clinical psychology requires continuous research to encourage integrative explanations for the complexity of mental disorders and their underlying causes. Biological evolutionary approaches have shown particular heuristic power for this endeavor. Life history theory (LHT) is an evolutionary model that incorporates novel and significant theoretical and empirical advances. However, there is a growing need for the incorporation of other successful evolutionary approaches. Thus, the goal of the present paper is to propose potential integrative connections between evolutionary causal modes, behavior systems, and LHT. For this, borderline personality disorder is used as an example of a condition that can be understood as an interaction between stress and attachment psychobiological systems (proximate causes), within the framework of ultimate causes clarified by LHT. To conclude, we will outline several aspects that could enhance the clinical field with implications for assessment and intervention.(AU)

Stimulation of tumor growth by human soluble intercellular adhesion molecule-1.

Because serum levels of soluble intercellular adhesion molecule-1 (sICAM-1) are elevated in cancer and sICAM-1 is angiogenic, we tested the ability of sICAM-1 to promote tumor growth. Our preliminary experiments showed that exogenous sICAM-1 significantly stimulated the growth of human tumors in vivo. Human fibrosarcoma transfectants, which express ICAM-1, produce ICAM-1 on the cell surface and release sICAM-1 into the medium without any apparent effect on cell growth in vitro. We found that conditioned medium from sense ICAM-1 transfectants compared with mock or antisense ICAM-1 transfectants stimulates endothelial cell migration in vitro and neovascularization in the chick chorioallantoic membrane assay. Tumor cells transfected with sense constructs form faster growing tumors than mock- and antisense-transfected cells in both chick embryos and nude mice models. Serum levels of human sICAM-1 from nude mice bearing sense ICAM-1 transfectants correlate positively with tumor weight. Sense ICAM-1 transfectants are more proliferative and induce more blood vessel formation than mock and antisense transfectants in nude mice. Because expression of ICAM-1 does not affect tumor cell growth in vitro, the angiogenic activity of sICAM-1 produced by sense ICAM-1 transfectants may be involved in the stimulation of tumor growth. Therefore, sICAM-1 may perform dual functions that are essential for tumor growth: angiogenesis and escape from immune surveillance.

Inhibition of bladder carcinoma angiogenesis, stromal support, and tumor growth by halofuginone.

We have previously demonstrated that halofuginone, a widely used alkaloid coccidiostat, is a potent inhibitor of collagen alpha1(I) and matrix metalloproteinase 2 gene expression. Halofuginone also suppresses extracellular matrix deposition and cell proliferation. We investigated the effect of halofuginone on transplantable and chemically induced mouse bladder carcinoma. In both systems, oral administration of halofuginone resulted in a profound anticancerous effect, even when the treatment was initiated at advanced stages of tumor development. Although halofuginone failed to prevent proliferative preneoplastic alterations in the bladder epithelium, it inhibited further progression of the chemically induced tumor into a malignant invasive stage. Histological examination and in situ analysis of the tumor tissue revealed a marked decrease in blood vessel density and in both collagen alpha1(I) and H19 gene expression. H19 is regarded as an early marker of bladder carcinoma. The antiangiogenic effect of halofuginone was also demonstrated by inhibition of microvessel formation in vitro. We attribute the profound antitumoral effect of halofuginone to its combined inhibition of the tumor stromal support, vascularization, invasiveness, and cell proliferation.

Characterization of the imprinted IPW gene: allelic expression in normal and tumorigenic human tissues.

IPW (Imprinted gene in the Prader-Willi syndrome region) is a recently identified paternally expressed gene. Previous work has demonstrated IPW expression in the human fetus and adult, with monoallelic expression in adult lymphoblasts and fibroblasts, and in fetal tissues. To further examine the expression of IPW, a series of experiments were carried out using RT-PCR to measure IPW expression in placentae and various fetal and tumor tissues. Biallelic expression of IPW was found in testicular germ cell tumor and bladder cancer cells, suggesting loss of imprinting in the latter case. Both H19 and Insulin-like growth Factor 2 (IGF2), two additional imprinted genes, also showed biallelic expression in those same tumors that demonstrated IPW biallelic expression. Of note, the naturally occurring parthenogenetic-derived mature teratoma unexpectedly expressed large amounts of IPW. Lastly, the pluripotent embryonal cancer cell line Tera-2 expressed IPW at the same level before and after differentiation induced by retinoic acid, suggesting that this gene functions in a 'housekeeping' capacity throughout cell growth. This was in contradistinction to H19 and IGF2, both of which showed significant transcriptional upregulation after Tera-2 cell differentiation.

H19 expression and tumorigenicity of choriocarcinoma derived cell lines.

Certain embryonal tumors demonstrate a loss of heterozygosity at the parentally imprinted region of chromosome 11p15.5. It has been hypothesized that this implicates a tumor suppressor gene at this locus. The human H19 gene maps to 11p15.5, is expressed in fetal tissues including the placenta and is paternally imprinted. Here we show that the abundance of H19 transcripts in cells of two choriocarcinoma derived cell lines (JAr and JEG-3) differs greatly. While JAr cells express high levels of H19 RNA, the expression of H19 in JEG-3 cells is much lower than that of normal trophoblasts. Cells of these two cell lines were subcutaneously injected into nude mice with subsequent tumor formation. A fivefold increase in the H19 RNA level was measured in tumors derived from JEG-3 cell lines as compared to these cells before injection. However this increase in H19 RNA did not alter the clonogenicity in soft agar nor the growth rate of the cells derived from these tumors as compared to the original JEG-3 cells. Nevertheless, the cells retaining the elevated level of H19 transcripts were more tumorigenic than the original cells. We propose that there is a selection of cells expressing high levels of H19 from the total JEG-3 cell population during the microevolution of tumor formation. These observations, together with our previous publications on H19 expression in human cancers, do not support the notion of a tumor suppressor role for the H19 gene.

Inhibition of matrix metalloproteinase-2 expression and bladder carcinoma metastasis by halofuginone.

Matrix metalloproteinase-2 (MMP-2) plays a critical role in tumor cell invasion and metastasis. Inhibitors of this enzyme effectively suppress tumor metastasis in experimental animals and are currently being tested in clinical trials. MMP-2 transcriptional regulation is a part of a delicate balance between the expression of various extracellular matrix (ECM) constituents and ECM degrading enzymes. Halofuginone, a low-molecular-weight quinazolinone alkaloid, is a potent inhibitor of collagen type alpha1 (I) gene expression and ECM deposition. We now report that expression of the MMP-2 gene by murine (MBT2-t50) and human (5637) bladder carcinoma cells is highly susceptible to inhibition by halofuginone. Fifty percent inhibition was obtained in the presence of as little as 50 ng/ml halofuginone. This inhibition is due to an effect of halofuginone on the activity of the MMP-2 promoter, as indicated by a pronounced suppression of chloramphenicol acetyltransferase activity driven by the MMP-2 promoter in transfected MBT2 cells. There was no effect on chloramphenicol acetyltransferase activity driven by SV40 promoter in these cells. Halofuginone-treated cells failed to invade through reconstituted basement-membrane (Matrigel) coated filters, in accordance with the inhibition of MMP-2 gene expression. A marked reduction (80-90%) in the lung colonization of MBT2 bladder carcinoma cells was obtained after the i.v. inoculation of halofuginone-treated cells as compared with the high metastatic activity exhibited by control untreated cells. Under the same conditions, there was almost no effect of halofuginone on the rate of MBT2 cell proliferation. These results indicate that the potent antimetastatic activity of halofuginone is due primarily to a transcriptional suppression of the MMP-2 gene, which results in a decreased enzymatic activity, matrix degradation, and tumor cell extravasation. This is the first description, to our knowledge, of a drug that inhibits experimental metastasis through the inhibition of MMP-2 at the transcriptional level. Combined with its known inhibitory effect on collagen synthesis and ECM deposition, halofuginone is expected to exert a profound anticancerous effect by inhibiting both the primary tumor stromal support and metastatic spread.

The expression of the imprinted H19 and IGF-2 genes in human bladder carcinoma.

The imprinted H19 gene is highly expressed in human embryos, fetal tissues and is nearly completely shut off in adults. However, it is reexpressed in a number of tumors including bladder carcinoma, demonstrating that H19 RNA is an oncofetal RNA. Tumors induced by injection of bladder carcinoma cell lines express H19 in contrast to the cells before injection. These observations support the notion of a positive correlation between H19 expression and bladder carcinoma. Loss of imprinting of H19 and IGF-2 was observed in samples of human bladder carcinoma.

Mammalian heparanase as mediator of tumor metastasis and angiogenesis.

Expression of heparan sulfate-degrading endoglycosidases, commonly referred to as heparanases, correlates with the metastatic potential of tumor cell lines, and treatment with heparanase inhibitors markedly reduces the incidence of metastasis in experimental animals. We purified a 50 kDa heparanase from human hepatoma and placenta and cloned a cDNA and gene encoding a protein of 543 amino acids. Only one heparanase sequence was identified, suggesting that this enzyme is the dominant endoglucuronidase in mammalian tissues. Expression of the cloned cDNA in insect and mammalian cells yielded 65 kDa and 50 kDa recombinant proteins. The 50 kDa enzyme represents an N-terminal processed enzyme that is at least 200-fold more active than the full-length 65 kDa form. Processing was demonstrated following incubation of the full-length recombinant enzyme with intact tumor cells. The heparanase mRNA and protein are preferentially expressed in metastatic cell lines and in specimens of human melanomas and carcinomas. In the colon, both the heparanase mRNA and protein are expressed already at the stage of tubulovillous adenoma, but not in the adjacent 'normal-looking' colon epithelium. Non-metastatic murine T lymphoma and melanoma cells transfected with the heparanase gene acquired a highly metastatic phenotype in vivo. Apart from its involvement in the egress of cells from the vasculature, heparanase is tightly involved in angiogenesis, both directly--by promoting invasion of endothelial cells (vascular sprouting), and indirectly--by releasing heparan sulfate-bound basic fibroblast growth factor, and generating HS degradation fragments that promote bFGF activity. The angiogenic potential of heparanase was demonstrated in vivo (Matrigel plug assay) by showing a three to fourfold increase in neovascularization induced by Eb T lymphoma cells following their transfection with the heparanase gene. The ability of heparanase to promote both tumor angiogenesis and metastasis makes it a promising target for cancer therapy.

[Experience with using high doses of cerebrolysin in vascular dementia]. / Opyt primeneniia vysokikh doz tserebrolizina pri sosudistoi dementsii.

The efficacy and tolerability of high-dose neurotrophic drug cerebrolysin was studied in 20 patients with vascular dementia diagnosed by criteria NINDS-AIREN and DSM-IV. The drug was well tolerated, affected positively cognitive function, especially neurodynamic processes. EEG featured after treatment intensification of rapid rhythms power and a decrease in delta-activity spectrum. The highest effect of cerebrolysin was achieved in patients with mild cognitive defects.

[The use of nimodipine in elderly dementia patients]. / Ispol'zovanie nimodipina u pozhilykh bol'nykh s dementsiei.

The analysis of original and literature evidence on nimodipin administration in senile patients with vascular dementia and Alzheimer's disease allows the conclusion on positive effects of the drug on cognitive, motor, behavioral, neuropsychological and postural defects. Further efforts should be directed to the study of long-term regimens and elucidation of nimodipin ability to inhibit progression of dementia.

Prevalencia de anticuerpos anti-Leptospira spp. en personas con exposición laboral en el departamento del Tolima / Prevalence of anti-Leptospira spp. antibodies among people with occupational exposure in Tolima department / Prevalência de anticorpos anti-Leptospira spp. em pessoas com exposição laboral no Departamento do Tolima

Objetivo: estimar la prevalencia de anticuerpos IgM contra Leptospira spp., mediante el Ensayo de Inmunoabsorción Ligado a Enzimas (ELISA), en la población de riesgo laboral de 8 municipios del Tolima. Metodología: se obtuvieron muestras de sangre de 261 empleados, las cuales fueron analizadas mediante la técnica de elisa para la detección de anticuerpos IgM anti-Leptospira spp., seguido de MAT y serotipificación. Resultado : se estimó una seroprevalencia del 25,29%, con una seroreactividad mayor en trabajadores de plantas de beneficio animal (34,2%), recolección de residuos sólidos (27,1%) y trabajadores de acueducto y alcantarillado (14,8%). La actividad en plantas de beneficio animal se identificó como factor de riesgo de Leptospira spp. (OR=1,86). Los serovares identificados fueron L. Bratislava (16), Ballum (5), Tarassovi (3), Hebdomadis (2), Sejroe (2) y Icterhemorragiae (1). El municipio de Libano presentó el mayor porcentaje de positividad (36,96%), seguido de Espinal y Guamo con 28,57% cada uno. Discusión: La evaluación del sistema de vigilancia indicó deficiencia en recursos y debilidades de los profesionales de la salud al desconocer los procedimientos, investigación, diagnóstico y notificación de la enfermedad. Conclusión: la leptospirosis está presente en poblaciones de riesgo laboral en el Tolima y se hace necesario abordar esta problemática en la población de otros municipios y los animales transmisores de la enfermedad.

Objective: to estimate the prevalence of IgM antibodies against Leptospira spp. Using the enzyme-linked immunosorbent assay (elisa) in a population at occupational risk from 8 municipalities of the Tolima department, Colombia. Methodology: blood samples were collected from 261 employees and analyzed with the elisa technique to detect IgM and anti-Leptospira spp. antibodies. This was followed by mat and serotyping. Result: a seroprevalence of 25.29% was estimated, with higher seroreactivity for individuals working at slaughter plants (34.2%), collecting solid waste (27.1%) and those in contact with water and sewage waste (14.8%). Activity in slaughter plants was identified as a risk factor for Leptospira spp. (OR = 1.86). The serovars identified were L. Bratislava (16), Ballum (5), Tarassovi (3), Hebdomadis (2), Sejroe (2), and Icterhemorragiae (1). The municipality of Libano had the highest percentage of positivity (36.96%), followed by Espinal and Guamo with 28.57% each. Discussion: assessment of the current surveillance system for leptospirosis indicated deficient resources and health professionals who are lacking in terms of knowledge regarding appropriate procedures, research on, diagnosis and reporting mechanisms for the disease. Conclusions: leptospirosis is present in public workers with occupational hazard in Tolima. In addition, this issue should be approached while taking into account the population from other municipalities as well as the animals associated with its transmission

Objetivo: estimam a prevalência de anticorpos IgM contra Leptospira spp., por ensaio de ensaio de imunossorvente ligado a enzima (ELISA) na população de risco ocupacional de 8 municípios de Tolima. Metodologia: Coletaram-se amostras de sangue de 261 empregados, e analisaram-se com a técnica de ELISA para detectar anticorpos IgM anti-Leptospira spp., seguido de MAT e de serotipificação. Resultados : estimou-se uma seroprevalência de 25,29%, com seroatividade superior nos trabalhadores dos matadouros (34,2%), da recolecção de lixo sólido (27,1%), e nos trabalhadores dos esgotos (14,8%). A atividade nos matadouros foi identificada como fator de risco de Leptospira spp. (OR=1,86). Os serovares identificados foram L. Bratislava (16), Ballum K(5), Tarassovi K(3), Hebdomadis (2), Sejroe (2) e Icterhemorragiae (1). O município de Libano apresentou a percentagem mais alta de positividade (36,96%), seguido por Espinal e por Guamo, com 28,57 cada um. Discussão: a avaliação do sistema de vigilância revelou deficiência de recursos e fraquezas dos profissionais da saúde, porque desconhecem os procedimentos, a investigação, o diagnóstico e a notificação da doença. Conclusão: a leptospirosis está nas populações de risco laboral no Departamento do Tolima, o que faz necessário acometer este problema na população de outros municípios e nos animais transmissores da doença.