Influence of the typology and timing of childhood trauma in psychoticism.

PURPOSE: Child maltreatment (CM) is associated with psychosis; however little is known about the frequency, type, and timing of abuse in the personality pathology domain of psychoticism (PSY) in the DSM-5. The purpose of this study was to analyze childhood trauma typology and frequency according to gender and to identify sensitive periods of susceptibility to CM in women with high PSY. METHODS: The Maltreatment and Abuse Chronology Exposure (MACE) scale was used to evaluate the frequency, severity and timing of each type of maltreatment. The full sample consisted of 83 participants with different psychiatric diagnoses. Psychoticism was assessed with the DSM-5 Personality Inventory (PID-5). To identify the differences in CM exposure between the PSY+ (high psychoticism) and PSY- (low psychoticism) groups, the Mann-Whitney U test, the chi square test and random forest (RF) test were used. RESULTS: Comparing PSY + and PSY-, revealed gender differences in the impact of abuse, with highly frequent and severe types of abuse, in women. In women, PSY + and PSY-, were differentiated especially in non-verbal emotional abuse, peer physical bullying and parental verbal abuse. Several periods with a major peak at age seven followed by peaks at age 17 and 12 years old were identified. CONCLUSION: Increased exposure to CM occurs in women with PSY+. A sensitivity to CM exposure during early childhood and late adolescence could be a risk factor for psychoticism in women.

Mathematical modeling for operative improvement of the decoloration of Acid Red 27 by a novel microbial consortium of Trametes versicolor and Pseudomonas putida: A multivariate sensitivity analysis.

In this work, it is presented a first approach of a mathematical and kinetic analysis for improving the decoloration and further degradation process of an azo dye named acid red 27 (AR27), by means of a novel microbial consortium formed by the fungus Trametes versicolor and the bacterium Pseudomonas putida. A multivariate analysis was carried out by simulating scenarios with different operating conditions and developing a specific mathematical model based on kinetic equations describing all stages of the biological process, from microbial growth and substrate consuming to decoloration and degradation of intermediate compounds. Additionally, a sensitivity analysis was performed by using a factorial design and the Response Surface Method (RSM), for determining individual and interactive effects of variables like, initial glucose concentration, initial dye concentration and the moment in time for bacterial inoculation, on response variables assessed in terms of the minimum time for: full decoloration of AR27 (R1 = 2.375 days); maximum production of aromatic metabolites (R2 = 1.575 days); and full depletion of aromatic metabolites (R3 = 12.9 days). Using RSM the following conditions improved the biological process, being: an initial glucose concentration of 20 g l-1, an initial AR27 concentration of 0.2 g l-1 and an inoculation moment in time of P. putida at day 1. The mathematical model is a feasible tool for describing AR27 decoloration and its further degradation by the microbial consortium of T. versicolor and P. putida, this model will also work as a mathematical basis for designing novel bio-reaction systems than can operate with the same principle of the described consortium.

Pretreatment Processes of Biomass for Biorefineries: Current Status and Prospects.

This article seeks to be a handy document for the academy and the industry to get quickly up to speed on the current status and prospects of biomass pretreatment for biorefineries. It is divided into two biomass sources: vegetal and animal. Vegetal biomass is the material produced by plants on land or in water (algae), consuming sunlight, CO2, water, and soil nutrients. This includes residues or main products from, for example, intensive grass crops, forestry, and industrial and agricultural activities. Animal biomass is the residual biomass generated from the production of food from animals (e.g., manure and whey). This review does not mean to include every technology in the area, but it does evaluate physical pretreatments, microwave-assisted extraction, and water treatments for vegetal biomass. A general review is given for animal biomass based in physical, chemical, and biological pretreatments.

A metabolomic approach shows sphingosine 1-phosphate and lysophospholipids as mediators of the therapeutic effect of liver growth factor in emphysema.

Tobacco smoke exposure is the principal cause of lung tissue destruction, which in turn results in emphysema that leads into shortness of breath. Liver growth factor (LGF, a cell and tissue regenerating factor with therapeutic activity in several organs) has antifibrotic and antioxidant properties that could be useful to promote lung tissue regenerating capacity in damaged lungs. The current study has examined differences in metabolite profiles (fingerprints) of plasma from mice (strain C57BL/6J, susceptible to develop emphysema) exposed to tobacco smoke during six months. One group of mice received a treatment with Liver Growth Factor (LGF) after emphysema was established, whereas the other group did not receive the treatment. Age and sex-matched mice not exposed to smoke were also maintained with or without treatment as controls. Metabolic fingerprints (untargeted analysis) of plasma after protein precipitation were obtained by LC-QTOF-MS. The signals were processed and a large number of possible metabolites were found (23944). Multivariate data analysis provided models that highlighted the differences between control and smoke exposed mice in both conditions. Accurate masses of features (possible compounds) representing significant differences were searched using online public databases. Lipid mediators, related to intracellular signaling in inflammation, were found among the metabolites putatively identified as markers of the different conditions and among them, sphingosine, sphingosine 1-phosphate and lysophospholipids point at the relevance of such metabolites in the regulation of the processes related to tissue regeneration mediated by LGF. These results also suggest that metabolomic fingerprinting could potentially guide the characterization of relevant metabolites leading the regeneration of lungs in emphysema disease.

Role of hydrogen sulfide in the pain processing of non-diabetic and diabetic rats.

Hydrogen sulfide (H2S) is a gasotransmitter endogenously generated from the metabolism of L-cysteine by action of two main enzymes called cystathionine ß-synthase (CBS) and cystathionine γ-lyase (CSE). This gas has been involved in the pain processing and insulin resistance produced during diabetes development. However, there is no evidence about its participation in the peripheral neuropathy induced by this metabolic disorder. Experimental diabetes was induced by streptozotocin (50mg/kg, i.p.) in female Wistar rats. Streptozotocin injection increased formalin-evoked flinching in diabetic rats as compared to non-diabetic rats after 2 weeks. Peripheral administration of NaHS (an exogenous donor of H2S) and L-cysteine (an endogenous donor of H2S) dose-dependently increased flinching behavior in diabetic and non-diabetic rats. Contrariwise, hydroxylamine (HA, a CBS inhibitor) and DL-propargylglycine (PPG, a CSE inhibitor) decreased formalin-induced nociceptive behavior in both experimental groups. In addition, an ineffective dose of HA and PPG partially prevented the L-cysteine-induced hyperalgesia in diabetic and non-diabetic rats. Interestingly, HA and PPG were three order of magnitude more potent in diabetic rats respect to non-diabetic rats, whereas NaHS was ten times more potent in the streptozotocin-diabetic group. Nine to 11 weeks after diabetes induction, tactile allodynia was observed in the streptozotocin-injected rats. On this condition, subcutaneous administration of PPG or HA reduced tactile allodynia in diabetic rats. Paradoxically, H2S levels were decreased in nerve sciatic, dorsal root ganglion and spinal cord, but not paw nor blood plasma, during diabetes-associated peripheral neuropathy development. Collectively, results suggest that H2S synthesized by CBS and CSE participate in formalin-induced nociception in diabetic and non-diabetic rats, as well as; in tactile allodynia in streptozotocin-injected rats. In addition, data seems to indicate that diabetic rats are more sensible to H2S-induced hyperalgesia than normoglycemic rats.

Optimization and validation of a CE-LIF method for amino acid determination in biological samples.

There is increasing evidence that amino acids and related compounds are among the most important metabolites for living systems and their quantitative analysis is a continuous challenge for clinical and biochemical laboratories. The lack of chromophore group and their high polarity make the analytical process more difficult. A simple, rapid and inexpensive procedure based on CE-LIF has been optimised for biological samples such as urine and hippocampus tissue in terms of sample treatment, separation and quantitation. Around 30min were required for derivatization and determination by CE-LIF of l-alanine, l-aspartate, l-ß-aminoisobutyrate, d-ß-aminoisobutyrate, glycine, l-glutamate, l-glutamine, l-histidine, l-isoleucine, l-leucine, l-methionine, l-ornithine, l-phenylalanine, 4-hydroxy-l-proline, l-proline, l-serine, d-serine, taurine, threonine and l-valine. 4-Fluoro-7-nitro-2,1,3-benzoxadiazole (NBD-F) is the labelling agent used for obtaining fluorescence derivatives stables in urine up to 12h and up to 24h in hippocampus extracts in refrigerated conditions. Electrophoretic conditions were: 90mM borate buffer at pH 10.25 prepared with 12.5mM native ß-cyclodextrin. Applied voltage was +21kV. The method was validated for a representative group of amino acids in urine: l-phenylalanine, glycine, l-serine, d-serine and taurine. In hippocampus tissue the method was validated for the neurotransmitters: gamma-aminobutyric acid, l-glutamine, glycine, l-glutamate and l-aspartate. The method has been successfully applied to real samples, seven amino acids were quantified in 16 urine samples from healthy and type I diabetic children living in Spain, aged 8-11, and the results were statistically compared. They were in accordance to published reference values. Moreover neurotransmitters in hippocampus extracts were determined in samples of control mice and reported results were in accordance with previous references.

Gastroprotective effect of Hintonia latiflora and Hintonia standleyana aqueous extracts and compounds.

ETHNOPHARMACOLOGICAL RELEVANCE: The stem-barks of Hintonia latiflora and Hintonia standleyana, locally known as "copalchi", are used for treating several maladies such as diabetes and gastrointestinal complaints, including gastric ulcers. Although the antidiabetic properties have been demonstrated, the gastroprotective action remains unexplored. AIM OF THE STUDY: The main goals of this study were to establish the potential acute toxicity and the gastroprotective activity of aqueous extracts and compounds from Hintonia latiflora and Hintonia standleyana in order to demonstrate their preclinical efficacy for the treatment of gastric ulcers in Mexican folk medicine. MATERIALS AND METHODS: The aqueous extracts from the stem-barks (HLSB and HSSB) and leaves (HLL and HSL) from Hintonia latiflora and Hintonia standleyana were prepared by infusion. Investigation of the acute toxicity was accomplished by the Lorke method. The gastroprotective effect was assessed by means of a conventional ethanol-induced gastric injury model in rats using carbenoxolone as positive control. 5-O-[ß-D-apiofuranosyl-(1→6)-ß-D-glucopyranosyl]-7-methoxy-3',4'-dihydroxy-4-phenylcoumarin (1) and chlorogenic acid (2) were also assayed. Preliminary mechanism of action of the tested compounds was analyzed using the same pharmacological models but pretreating the animals with N(G)-nitro-L-arginine methyl ester (L-NAME), N-ethylmaleimide (NEM) and indomethacin. RESULTS: Investigation of the acute toxicity revealed that infusions of the leaves and stem-barks of both Hintonia species were not toxic to mice (LD(50)>5000 mg/kg in all cases). HLSB, HSSB, HLL and HSL provoked a significant gastroprotective effect [80.5±3.35% (ED(50)=184.7 mg/kg), 80.26±3.96%, 75.1±7.26% (ED(50)=109.1 mg/kg), 76.85±3.17% (ED(50)=149.7 mg/kg) of gastroprotection respectively]. Compounds 1 and 2, present in all the extracts, were also active [68.85±8.4% (ED(50)=15 mg/kg), 74.04±4.4% (ED(50)=26 mg/kg) of gastroprotection respectively] and their mode of action involved non-protein sulfhydryl endogenous (NP-SH) compounds, since only pretreatment with NEM inhibited their gastroprotective action. CONCLUSIONS: The present investigation tends to support the ethnomedical use of HLSB, HSSB for treating gastric ulceration. Since HLL and HSL were also active, the leaves could be use alternatively, which in terms of natural resources conservation is an outstanding finding, considering that the plant populations of both Hintonia are scarce and in danger of extinction. Mainly two compounds (1 and 2) are important active principles of the plants.

First molecular identification of Diphyllobothrium dendriticum plerocercoids from feral rainbow trout (Oncorhynchus mykiss) in Chile.

Between April and June 2009, 1,075 feral rainbow trout from 10 different lakes involved with aquaculture activities in Los Lagos Region, Chile, were inspected for Diphyllobothrium species. All viscera and muscles of the fish were examined using stereomicroscopy; pyloric cecae and stomachs infected with plerocercoids were checked by histology and scanning electron microscopy. Plerocercoids of Diphyllobothrium dendriticum were confirmed by PCR and sequencing of COI and 18S rRNA + ITS1 + 5.8S rRNA + ITS2 genes for the first time in Chile. Overall prevalence of plerocercoids of D. dendriticum was 9.2% (99/1,075) in Los Lagos Region and 17.4% (99/570) for Chiloe Island. Plerocercoids were not detected in the continental lakes of the Los Lagos Region (Chapo, Rupanco, and Llanquihue). Tarahuín Lake exhibited a prevalence of 50.9% (81/159), Cucao Lake 5.1% (4/79), Natri Lake 4.7% (5/107), Huillinco Lake 3.6% (5/138), and San Antonio Lake 66.7% (4/6). Abundance was 1.1 plerocercoid larvae per fish (1,169 larvae/1,075 fish). All the plerocercoids were found encysted in the viscera of the fish. Plerocercoids were 10.9 ± 3 (7-16) mm long by 0.4 ± 0.2 (0.2-0.6) mm wide. The scolex was enlarged, with 2 bothria and a frontal pit. The body was covered with short capilliform filitriches, 4-6 mm long. The Chilean COI and 18SrRNA + ITS1 + 5.8SrRNA + ITS2 gene sequences indicated 96.34-96.52% and 99% similarity with D. dendriticum sequences, respectively. Diphyllobothrium dendriticum is reported for the first time in freshwater ecosystems as far as 43 ° S on Chiloe Island. These findings and previous reports of plerocercoids of Diphyllobothrium spp. in farmed rainbow trout at Tarahuín Lake support the putative life cycle of this parasite in lakes of southern Chile where there are aquaculture activities.

Immunoprotective effect of von Willebrand factor towards therapeutic factor VIII in experimental haemophilia A.

The development of inhibitory anti-factor VIII (FVIII) antibodies in patients with haemophilia A following replacement therapy is associated with several types of risk factors. Among these, the purity of FVIII concentrates, and in particular the presence of von Willebrand factor (VWF), was controversially proposed to influence the immunogenicity of exogenous FVIII. We re-assessed in vivo and in vitro the immuno-protective effect of VWF towards FVIII. The immuno-protective effect of VWF towards FVIII was investigated in vivo, in a model of haemophilia A. We studied the endocytosis of FVIII by murine bone marrow-derived dendritic cells and evaluated the capacity of VWF to block the internalization of FVIII. We characterized the relevance of VWF for the accumulation of FVIII in the marginal zone of the spleen, a secondary lymphoid organ where the immune response to therapeutically administered FVIII initiates. Our results confirm that VWF reduces the immunogenicity of FVIII in FVIII-deficient mice. Paradoxically, VWF is important for the accumulation of FVIII in the marginal zone of the spleen. We propose that VWF exerts at least two non-mutually exclusive immunoprotective roles towards FVIII in haemophilic mice: VWF prevents the endocytosis of FVIII by professional antigen-presenting cells by blocking the interaction of FVIII with as yet unidentified endocytic receptor(s). Hypothetically, VWF, by virtue of increasing the half-life of FVIII in the circulation, may allow an increased contact time with tolerogenic marginal zone B cells in the spleen.

mRNA expression in rabbit blastocyst and endometrial tissue of candidate gene involved in gestational losses.

Gestation is a complex process that involves different growth factors, cytokines and adhesion proteins related with embryo development, cellular differentiation and proliferation, embryo-endometrium interaction, angiogenesis, maternal-embryonic recognition and growth development of placenta and embryos. In this study, we examine pre-implantational (at 6 days of gestation) and gestational (at 12 days and total from ovulation to birth) losses in two rabbit lines selected by different criteria (post-weaning daily gain and litter size) and the pattern of a set of candidate transcripts, at 6 days of gestation, related with embryo development and implantation process, such as Oct-4, epidermal growth factor receptor 3 (erbB3), Transforming Growth Factor ß2, Vascular Endothelial Growth Factor and Interferon γ and related with insulin-like growth factors signalling as insulin growth factors I and II and their receptors in rabbit blastocysts and endometrial tissue. Similar pre-implantational losses were obtained in both lines. However, the gestational losses of the line selected by post-weaning daily gain clearly mirrored an increase in losses by 50% at 12 days and at birth (22.4 vs 9.5 and 50.2 vs 25.4, respectively, between line selected by post-weaning daily gain and line selected by litter size). In blastocysts and endometrial tissue at 6 days of gestation qRT-PCR assays indicated that the mean insulin-like growth factor (IGF)-IIR mRNA expression was down-regulated in line selected by post-weaning daily gain. Dysregulation of the IGF-IIR could be potential reasons for induced gestational losses. We conclude that IGF-IIR gene expression in blastocyst and endometrial tissue at 6th day of gestation tends to decline in line selected by post-weaning daily gain. The functional significance related with gestational losses is uncertain.

Prognostic evaluation of febrile neutropenia in apparently stable adult cancer patients.

UNLABELLED: ` BACKGROUND: Predictive models to identify low-risk febrile neutropenia (FN) have been developed with heterogeneous samples, which included stable and unstable patients, solid tumours, acute leukaemia and bone marrow transplantation. These models fail to recognise 5-15% of cases with unexpected complications, and literature specifically addressing apparently stable patients (ASPs) is scarce. METHODS: We reviewed 861 episodes of FN in outpatients with solid tumours, including 692 (80%) episodes with apparent clinical stability. We aimed to investigate the prognosis of this latter group and explore the possibility of stratifying it according to the presenting features. A case-control study was performed and the MASCC index was evaluated. RESULTS: The rates of complications and bacteraemia in ASPs were 7.3% and 6.2%, respectively. The MASCC index yielded a low sensitivity to detect complications (36%). Prognostic factors were identified: ECOG performance status ≥2, chronic bronchitis, chronic heart failure, stomatitis NCI grade ≥2, monocytes <200 mm(-3) and stress hyperglycaemia. CONCLUSION: A very simple assessment is useful to classify the patients with FN according to the risk of complications. A few additional variables may predict the clinical course of the patients. We additionally show that the MASCC index applied to this specific group has a low sensitivity to predict complications.

First Report of Passalora Leaf Spot Caused by Passalora bougainvilleae on Bougainvillea in Mexico.

Bougainvillea (Bougainvillea spectabilis Willd) growing in 28 gardens during 2009 showed 100% disease incidence and 3 to 7% disease severity. Bougainvilleas with white flowers were the most affected. Symptoms consisted of light brown spots with dark brown margins visible on adaxial and abaxial sides of the leaves. Spots were circular, 2 to 7 mm in diameter, often surrounded by a chlorotic halo, and delimited by major leaf veins. Single-spore cultures were incubated at 24°C under near UV light for 7 days to obtain conidia. Pathogenicity was confirmed by spraying a conidial suspension (1 × 104 spores/ml) on leaves of potted bougainvillea plants (white, red, yellow, and purple flowers), incubating the plants in a dew chamber for 48 h and maintaining them in a greenhouse (20 to 24°C). Identical symptoms to those observed at the residential gardens appeared on inoculated plants after 45 to 60 days. The fungus was reisolated from inoculated plants that showed typical symptoms. No symptoms developed on control plants treated with sterile distilled water. The fungus produced distinct stromata that were dark brown, spherical to irregular, and 20 to 24 µm in diameter. Conidiophores were simple, born from the stromata, loose to dense fascicles, brown, straight to curved, not branched, zero to two septate, 14 × 2 µm, with two to four conspicuous and darkened scars. The conidia formed singly, were brown, broad, ellipsoid, obclavate, straight to curved with three to four septa, 40 × 4 µm, and finely verrucous with thick hilum at the end. Fungal DNA from the single-spore cultures was obtained using a commercial DNA Extraction Kit (Qiagen, Valencia, CA); ribosomal DNA was amplified with ITS5 and ITS4 primers and sequenced. The sequence was deposited at the National Center for Biotechnology Information Database (GenBank Accession Nos. HQ231216 and HQ231217). The symptoms (4), morphological characteristics (1,2,4), and pathogenicity test confirm the identity of the fungus as Passalora bougainvilleae (Muntañola) Castañeda & Braun (= Cercosporidium bougainvilleae Muntañola). This pathogen has been reported from Argentina, Brazil, Brunei, China, Cuba, El Salvador, India, Indonesia, Jamaica, Japan, Thailand, the United States, and Venezuela (3). To our knowledge, this is the first report of this disease on B. spectabilis Willd in Mexico. P. bougainvilleae may become an important disease of bougainvillea plants in tropical and subtropical areas of Mexico. References: (1) U. Braun and R. R. Castañeda. Cryptogam. Bot. 2/3:289, 1991. (2) M. B. Ellis. More Dematiaceous Hypomycetes. Commonwealth Mycological Institute, Kew, Surrey, UK, 1976. (3) C. Nakashima et al. Fungal Divers. 26:257, 2007. (4) K. L. Nechet and B. A. Halfeld-Vieira. Acta Amazonica 38:585, 2008.

Resultado funcional de infiltración de toxina botulínica multinivel en extremidades inferiores y terapia integral en niños con parálisis cerebral espástica / Functional outcome of multilevel botulinum toxin infiltration of the lower limbs and comprehensive therapy in children with spastic cerebral palsy

Una de las alternativas terapéuticas para el manejo de la espasticidad en la parálisis cerebral es el uso de la toxina botulínica (TBA), la que mediante una denervación temporal permite reducir el tono muscular facilitando la movilidad voluntaria. A pesar de que existe abundante literatura médica, en su mayoría evidencia tipo ii, que apoye el uso de la TBA en el nivel de «actividad» de la Clasificación Internacional del Funcionamiento, de la Discapacidad y de la Salud, existe escasa evidencia científica que demuestre la influencia que esta terapia tiene en el nivel de «participación», lo que es el propósito de este estudio. Materiales y métodos. Ensayo clínico controlado aleatorio, simple ciego, con control a las 4 semanas, a los 3 meses y a los 6 meses. Treinta y seis niños con hemiplejia o diplejia espástica entre 3–10 años fueron asignados aleatoriamente con enmascaramiento en dos grupos: 1) grupo experimental: TBA tipo A más terapia integral y 2) grupo control: solo terapia integral. La medida de resultado principal fueron los ítems de autocuidado, movilidad y transferencias del instrumento Wee Functional Independence Measure. Como medida de resultado secundaria se utilizó Gross Motor Function Measure-88. Resultados. El puntaje integrado de autocuidado, movilidad y transferencias aumentó entre el momento basal y los 6 meses un 25% en el grupo control y un 15,1% en el grupo con TBA, respectivamente, no existiendo diferencias significativas en ambos grupos (p>0,3). El puntaje de Gross Motor Function Measure-88 en ambos grupos registró aumento, sin embargo, las pruebas no paramétricas indicaron que la distribución de los niños fue similar en ambos grupos durante el seguimiento, no existiendo diferencias estadísticamente significativas (U de Mann Whitney; p>0,10). Conclusión. No se observan en este estudio diferencias significativas en cuanto a independencia funcional y en función motora gruesa en ambos grupos (AU)

One of the therapeutic alternatives for the treatment of spasticity in cerebral palsy is the use of botulinum toxin, which, through a temporary denervation, makes it possible to reduce muscle tone, facilitating voluntary mobility. Even though there is abundant literature, mostly with type II evidence, that supports the use of botulinum toxin on the “activity” level of the International Classification of Functioning, Disability and Health, there is scant scientific evidence that demonstrates the influence this therapy has on the “participation” level, which is the purpose of this study. Material and methods. A randomized, single blind, controlled clinical trial with controls at 4 weeks, 3 and 6 months. Thirty-six children with hemiplegia or spastic diplegia between 3–10 years were randomly assigned with masking into two groups: experimental group with botulinum toxin A plus comprehensive therapy and control group with only comprehensive therapy. The primary endpoints measured were self-care, mobility and instrument transfer of the Wee Functional Independence Measure Instrument. The Gross Motor Function Measure-88 was used to measure the secondary results. Results. The weefim score of self-care, mobility and transfers increased 25.0% between baseline and 6 months in the control group and 15.1% in the botulinum toxin group, respectively, there being no statistically significant differences between both groups (p>0.3). An increase was recorded for the score on the Gross Motor Function Measure-88 in both groups. However, the non-parametric tests indicated that the distribution of the children was similar in both groups during the follow-up, there being no statistically significant differences (Mann Whitney U Test, p>0.10). Conclusion. No significant differences were observed in this study regarding functional independence and gross motor function in both groups (AU)

Posición oficial de la Sociedad Chilena de Climaterio para el manejo clínico de la mujer climatérica / Official position of the Chilean Society of Climacteric on the management of climacteric women

The health of many women is affected in the climacteric period, either by symp-toms that deteriorate their life quality (QL) or by chronic diseases that affect their life expectancy. Therefore, it is mandatory to evaluate these two aspects, having as core objectives for any eventual therapeutic intervention, the improvement of QL and the reduction of cardiovascular risk and fractures. To evaluate QL it is mandatory to follow structured interviews that weigh systematically climacteric symptoms such as the Menopause Rating Scale (MRS). The paradigm of the metabolic syndrome constitutes a suitable frame to evaluate cardiovascular risk. Age, a low body weight, a history of fractures and steroid use are risk factors for fractures. A proper evaluation will allow the detection of patients with a low QL or a high risk for chronic disease, therefore identifying those women who require therapy. The clinical management should include recommendations to improve lifestyles, increase physical activity, avoidance of smoking and to follow a low calorie diet rich in vegetables and fruits. Hormonal therapy is the most effcient treatment to improve the QL and its risk is minimized when it is used in low doses or by the transdermal route. Tibolone is an alternative, especially useful in patients with mood disorders and sexual dysfunction. Vaginal estrogens are also a good option, when urogenital symptoms are the main complaint. Some antidepressants can be an effective therapy in patients with vasomotor symptoms who are not willing or cannot use estrogens. The effectiveness of any alternative therapy for menopausal symptoms has not been demonstrated. Dyslipidemia, hypertension, obesity and insulin resistance should be managed ac-cording to guidelines. Calcium and vitamin D have positive effects on bone density and certain tendency to reduce vertebral fractures. Bisphosphonates decrease the risk of vertebral fractures.

Posición oficial de la Sociedad Chilena de climaterio para el manejo de la mujer climatérica / Official position of the Chilean Society of menopause for the management of climacteric women

La mayoría de las mujeres ve afectada su salud en el período climatérico, ya sea por sintomatología que le deteriora su calidad de vida (CV) o por la aparición de enfermedades crónicas que le afectan sus expectativas de vida. Por lo tanto, es básico evaluar estos dos aspectos, teniendo como objetivos centrales de las eventuales intervenciones terapéuticas, mejorar la CV y reducir el riesgo de enfermedades cardiovasculares y/o fracturas...

Splenic marginal zone antigen-presenting cells are critical for the primary allo-immune response to therapeutic factor VIII in hemophilia A.

BACKGROUND: Alloimmune responses to intravenously administered protein therapeutics are the most common cause of failure of replacement therapy in patients with defective levels of endogenous proteins. Such a situation is encountered in some patients with hemophilia A, who develop inhibitory anti-factor (F)VIII alloantibodies after administration of FVIII to treat hemorrhages. OBJECTIVES: The nature of the secondary lymphoid organs involved in the initiation of immune responses to human therapeutic has not been studied. We therefore investigated this in the case of FVIII, a self-derived exogenous protein therapeutic. METHODS: The distribution of intravenously administered FVIII was followed after FVIII-deficient mice were injected with radiolabeled FVIII and using immunohistochemistry. The role of the spleen and antigen-presenting cells (APC) in the onset of the anti-FVIII immune response was analyzed upon splenectomy or treatment of the mice with APC-depleting compounds. RESULTS: FVIII preferentially accumulated in the spleen at the level of metallophilic macrophages in the marginal zone (MZ). Surgical removal of the spleen or selective in vivo depletion of macrophages and CD11c-positive CD8 alpha-negative dendritic cells resulted in a drastic reduction in anti-FVIII immune responses. CONCLUSIONS: Using FVIII-deficient mice as a model for patients with hemophilia A, and human pro-coagulant FVIII as a model for immunogenic self-derived protein therapeutics, our results highlight the importance of the spleen and MZ APCs in the initiation of immune responses to protein therapeutics. Identification of the receptors implicated in retention of protein therapeutics in the MZ may pave the way towards novel strategies aimed at reducing their immunogenicity.

Ganglio centinela en cáncer gástrico: descripción de la técnica laparoscópica / Technique of laparoscopic sentinel node biopsy in gastric cancer

El estudio del ganglio centinela es un procedimiento actualmente aceptado en el melanoma, cáncer de pene y de mama. Su indicación y utilidad en el cáncer gástrico es aún controvertida. El objetivo del presente trabajo es describir la técnica de la biopsia laparoscópica del ganglio centinela en el cáncer gástrico y la posibilidad de su realización en el Hospital Universitario de Caracas. Se incluyeron dos pacientes durante el período comprendido entre enero y noviembre del 2008 con diagnóstico de carcinoma gástrico en estadio inicial. Se utilizó la técnica combinada con azul patente y tecnecio (Tc99). Una vez identificado el ganglio centinela se procedio a la cirugía habitual. El ganglio se evaluo posteriormente por anatomía patológica en conjunto con el espécimen quirúrgico. El porcentaje de detección del ganglio centinela fue del 50 por ciento. El ganglio centinela detectado fue positivo para metástasis. No hubo morbilidad asociada. La identificación del ganglio centinela por laparoscopia es aplicable en pacientes con cáncer gástrico en estadios iniciales y representa una opción en el abordaje terapéutico minimamente invasivo de dicha patología.

The prevalence of radiographic vertebral fractures in Latin American countries: the Latin American Vertebral Osteoporosis Study (LAVOS).

UNLABELLED: In the first population-based study of vertebral fractures in Latin America, we found a 11.18 (95% CI 9.23-13.4) prevalence of radiographically ascertained vertebral fractures in a random sample of 1,922 women from cities within five different countries. These figures are similar to findings from studies in Beijing, China, some regions of Europe, and slightly lower than those found in the USA using the same standardized methodology. INTRODUCTION: We report the first study of radiographic vertebral fractures in Latin America. METHODS: An age-stratified random sample of 1,922 women aged 50 years and older from Argentina, Brazil, Colombia, Mexico, and Puerto Rico were included. In all cases a standardized questionnaire and lateral X-rays of the lumbar and thoracic spine were obtained after informed consent. RESULTS: A standardized prevalence of 11.18 (95% CI 9.23-13.4) was found. The prevalence was similar in all five countries, increasing from 6.9% (95% CI 4.6-9.1) in women aged 50-59 years to 27.8% (95% CI 23.1-32.4) in those 80 years and older (p for trend < 0.001). Among different risk factors, self-reported height loss OR = 1.63 (95% CI: 1.18-2.25), and previous history of fracture OR = 1.52 (95% CI: 1.14-2.03) were significantly (p < 0.003 and p < 0.04 respectably) associated with the presence of radiographic vertebral fractures in the multivariate analysis. In the bivariate analyses HRT was associated with a 35% lower risk OR = 0.65 (95% CI: 0.46-0.93) and physical activity with a 27% lower risk of having a vertebral fracture OR = 0.73 (95% CI: 0.55-0.98), but were not statistically significant in multivariate analyses CONCLUSION: We conclude that radiographically ascertained vertebral fractures are common in Latin America. Health authorities in the region should be aware and consider implementing measures to prevent vertebral fractures.

[Cerebelous syndrome by infratentorial brain tuberculornas and mutisystemic tuberculosis in AIDS patient]. / Síndrome cerebeloso secundario a granulomas de fosa posterior y tuberculosis multisistémica en un paciente con SIDA.

We present a clinical case of a patient who consulted for a cerebelous syndrome and diplopia associated to 10 kg weight loss in six months and multiple adenopathies. Cerebral imagenology study evidenced the presence of granulamatous masses at the cerebellum and midbrain level, there were no cerebrospinal fluid abnormalities. Systemic tuberculosis (TB) diagnosis was done based in finding of acid-fast bacilli positive staining in urine and lymph node biopsy. HIV infection was documented by ELISA serology. CD4 cell count was 590 cell/mm3, classifying the case a AIDS Cl stage. TB was treated according to national guidelines leading to good clinical and imagenology evolution. The clinical case scenario of infratentorial tuberculomas without meningitis as a first manifestation of TB and AIDS is unusual, generating our interest in reporting this case.

Síndrome cerebeloso secundario a granulomas de fosa posterior y tuberculosis multisistémica en un paciente con SIDA / Cerebelous syndrome by infratentorial brain tuberculornas and mutisystemic tuberculosis in AIDS patient

Presentamos el caso clínico de un paciente que consultó por un síndrome cerebeloso y diplopía, asociados a pérdida de peso de 10 kilos en 6 meses y adenopatías múltiples. El estudio imagenológico cerebral demostró la presencia de lesiones de aspecto granulomatoso a nivel cerebeloso y mesencefálico, sin alteración citoquímica del líquido cefalorraquídeo. Las baciloscopias de orina y de la biopsia ganglionar fueron positivas y permitieron el diagnóstico de tuberculosis (TBC) sistémica. La serología para VIH resultó positiva en sangre con un recuento de linfocitos CD4 de 590 cel/mm3, clasificándose el caso como SIDA etapa Cl. El paciente fue tratado con el esquema antituberculoso según norma nacional, con buena respuesta clínica e imagenológica. La presentación de tuberculomas infratentoriales sin meningitis, como primera causa de pesquisa de TBC y SIDA no es habitual, de allí nuestro interés por comunicar el caso.

We present a clinical case of a patient who consulted for a cerebelous syndrome and diplopia associated to 10 kg weight loss in six months and multiple adenopathies. Cerebral imagenology study evidenced the presence of granulamatous masses at the cerebellum and midbrain level, there were no cerebrospinal fluid abnormalities. Systemic tuberculosis (TB) diagnosis was done based in finding of acid-fast bacilli positive staining in urine and lymph node biopsy. HIV infection was documented by ELISA serology. CD4 cell count was 590 cell/mm3, classifying the case a AIDS Cl stage. TB was treated according to national guidelines leading to good clinical and imagenology evolution. The clinical case scenario of infratentorial tuberculomas without meningitis as a first manifestation of TB and AIDS is unusual, generating our interest in reporting this case.