Hypomania: a transcultural perspective

This study examined the transcultural robustness of a screening instrument for hypomania, the Hypomania Checklist-32. first revised version(HCL-32 R1) It was carried out in 2606 patients from twelve countries in five geographic regions (Northern, Southern and Eastern Europe, South America and East Asia) In addition, GAMIAN Europe contributed data from its members Exploratory and confirmatory factor analyses were used to examine the transregional stability of the measurement properties of the HCL-32 R 1, including the influence of sex and age as covariates A cross cultures, a two-factor structure was confirmed the first factor (F 1) reflected the more positive aspects of hypomania (being more active, elated, self-confident, and cognitively, enhanced), the second factor (F2) reflected the more negative aspects (being irritable, impulsive, careless. more substance use). The measurement properties of the HCL-32 R1 were largely invariant across cultures Only few items showed transcultural differences in their relation to hypomania as measured by the test F2 was higher among men and in more severe manic syndromes, F1 was highest in North and East Europe and lowest in South America Vie scores decreased slightly with age The frequency of the 32 items showed remarkable similarities across geographic areas, with two exceptions. South Europeans had lower symptom frequencies in general and East Europeans higher rates of substance use These findings support the international applicability of the HCL-32 R1 as a screening instrument for hypomania

Neuronal Correlates of Brain-derived Neurotrophic Factor Val66Met Polymorphism and Morphometric Abnormalities in Bipolar Disorder

The brain-derived neurotrophic factor (BDNF) Val66Met polymorphism has been proposed as a possible candidate for involvement in the pathophysiology of bipolar disorder ( BD). To determine whether an association exists between the BDNF Val66Met genotype and morphometric abnormalities of the brain regions involved in memory and learning in BD and healthy subjects. Forty-two BD patients and 42 healthy subjects were studied. Interactions between BDNF Val66Met genotype and diagnosis in gray ( GM) volumes were analyzed using an optimized voxel-based morphometry technique. Declarative memory function was assessed with the California Verbal Learning Test II. Left and right anterior cingulate GM volumes showed a significant interaction between genotype and diagnosis such that anterior cingulate GM volumes were significantly smaller in the Val/Met BD patients compared with the Val/Val BD patients (left P = 0.01, right P = 0.01). Within-group comparisons revealed that the Val/Met carriers showed smaller GM volumes of the dorsolateral prefrontal cortex compared with the Val/Val subjects within the BD patient (P = 0.01) and healthy groups (left P = 0.03, right P = 0.03). The Val/Met healthy subjects had smaller GM volumes of the left hippocampus compared with the Val/Val healthy subjects (P<0.01). There was a significant main effect of diagnosis on memory function (P = 0.04), but no interaction between diagnosis and genotype was found (P = 0.48). The findings support an association between the BDNF Val66Met genotype and differential gray matter content in brain structures, and suggest that the variation in this gene may play a more prominent role in brain structure differences in subjects affected with BD. Neuropsychopharmacology (2009) 34, 1904-1913; doi: 10.1038/npp.2009.23; published online 18 March 2009

Cavopulmonary anastomosis improves left ventricular assist device support in acute biventricular failure

Objective: Right ventricular failure during left ventricular assist device (WAD) support can result in severe hemodynamic compromise with high mortality. This study investigated the acute effects of cavopulmonary anastomosis on right ventricular loading and WAD performance in a model of severe biventricular failure. Methods: LVAD support was performed by means of centrifugal pump implantation in 14 anesthetized dogs (20-30 kg) with severe biventricular failure obtained by ventricular fibrillation induction. Animals were randomized to be submitted to classical cavopulmonary anastomosis (Glenn shunt) or to control group and were maintained under WAD support for 2 h. Left and right atrial, right ventricular and systemic pressures were monitored, white total pulmonary flow was simultaneously recorded by transonic flowmeters located on the superior vena cava and pulmonary trunk. Blood gas and venous lactate determinations were also obtained. Results: Ventricular fibrillation maintenance resulted in acute WAD performance impairment after 90 min in the control group, while animals with Glenn circuit maintained normal WAD pump flow (55 +/- 13 ml kg(-1) min(-1) vs 21 +/- 4 ml kg(-1) min(-1), p < 0.001) and better peripheral perfusion (blood lactate of 29 +/- 10 pg/ml vs 46 +/- 9 pg/ml, p < 0.001). Left and right atrial pressures did not change significantly, while right ventricular pressure was tower in animals with Glenn circuit (13 +/- 3 mmHg vs 22 +/- 8 mmHg, p = 0.005). Right ventricular unloading with Glenn shunt also resulted in superior total pulmonary flow (59 +/- 13 ml kg(-1) min(-1) vs 17 +/- 3 ml kg(-1) min(-1), p < 0.001). Conclusion: The concomitant use of cavopulmonary anastomosis during LVAD support in a model of severe biventricular failure limited right ventricular overloading and resulted in better hemodynamic performance. (C) 2008 European Association for Cardio-Thoracic Surgery. Published by Elsevier B.V. All rights reserved.

Automatic versus manual pressure support reduction in the weaning of post-operative patients: a randomised controlled trial

Introduction Reduction of automatic pressure support based on a target respiratory frequency or mandatory rate ventilation (MRV) is available in the Taema-Horus ventilator for the weaning process in the intensive care unit (ICU) setting. We hypothesised that MRV is as effective as manual weaning in post-operative ICU patients. Methods There were 106 patients selected in the postoperative period in a prospective, randomised, controlled protocol. When the patients arrived at the ICU after surgery, they were randomly assigned to either: traditional weaning, consisting of the manual reduction of pressure support every 30 minutes, keeping the respiratory rate/tidal volume (RR/TV) below 80 L until 5 to 7 cmH(2)O of pressure support ventilation (PSV); or automatic weaning, referring to MRV set with a respiratory frequency target of 15 breaths per minute (the ventilator automatically decreased the PSV level by 1 cmH(2)O every four respiratory cycles, if the patient`s RR was less than 15 per minute). The primary endpoint of the study was the duration of the weaning process. Secondary endpoints were levels of pressure support, RR, TV (mL), RR/TV, positive end expiratory pressure levels, FiO(2) and SpO(2) required during the weaning process, the need for reintubation and the need for non-invasive ventilation in the 48 hours after extubation. Results In the intention to treat analysis there were no statistically significant differences between the 53 patients selected for each group regarding gender (p = 0.541), age (p = 0.585) and type of surgery (p = 0.172). Nineteen patients presented complications during the trial (4 in the PSV manual group and 15 in the MRV automatic group, p < 0.05). Nine patients in the automatic group did not adapt to the MRV mode. The mean +/- sd (standard deviation) duration of the weaning process was 221 +/- 192 for the manual group, and 271 +/- 369 minutes for the automatic group (p = 0.375). PSV levels were significantly higher in MRV compared with that of the PSV manual reduction (p < 0.05). Reintubation was not required in either group. Non-invasive ventilation was necessary for two patients, in the manual group after cardiac surgery (p = 0.51). Conclusions The duration of the automatic reduction of pressure support was similar to the manual one in the postoperative period in the ICU, but presented more complications, especially no adaptation to the MRV algorithm. Trial Registration Trial registration number: ISRCTN37456640

Brain structure and symptom dimension relationships in obsessive-compulsive disorder: A voxel-based morphometry study

Background: Obsessive-compulsive disorder (OCD) is a clinically heterogenous disorder characterized by temporally stable symptom dimensions. Past inconsistent results from structural neuroimaging studies of OCD may have resulted from the effects of these specific symptom dimensions as well as other socio-demographic and clinical variables upon gray matter (GM) volume. Methods: GM volume was measured in 25 adult OCD patients and 20 adult healthy controls using voxel-based morphometry (VBM), controlling for age and total brain GM volume. Univariate and multivariate regression analyses were carried out between regions of GM difference and age, age of onset, medication load, OCD severity, depression severity, and separate symptom dimension scores. Results: Significant GM volumetric differences in OCD patients relative to controls were found in dorsal cortical regions, including bilateral BA6, BA46, BA9 and right BA8 (controls > patients), and bilateral midbrain (patients > controls). Stepwise regression analyses revealed highly significant relationships between greater total OCD symptom severity and smaller GM volumes in dorsal cortical regions and larger GM volumes in bilateral midbrain. Greater age was independently associated with smaller GM volumes in right BA6, left BA9, left BA46 and larger GM volumes in right midbrain. Greater washing symptom severity was independently associated with smaller GM volume in right BA6, while there was a trend association between greater hoarding symptom severity and lower GM volume in left BA6. Limitations: The sample was relatively small to examine the relationship between symptom scores and GM volumes. Multiple patients were taking medication and had comorbid disorders. Conclusions: These analyses suggest dorsal prefrontal cortical and bilateral midbrain GM abnormalities in OCD that appear to be primarily driven by the effects of total OCD symptom severity. The results regarding the relationship between GM volumes and symptom dimension scores require examination in larger samples. (C) 2008 Elsevier B.V. All rights reserved.

ACCM/PALS haemodynamic support guidelines for paediatric septic shock: an outcomes comparison with and without monitoring central venous oxygen saturation

Introduction: The ACCM/PALS guidelines address early correction of paediatric septic shock using conventional measures. In the evolution of these recommendations, indirect measures of the balance between systemic oxygen delivery and demands using central venous or superior vena cava oxygen saturation ( ScvO(2) >= 70%) in a goal-directed approach have been added. However, while these additional goal-directed endpoints are based on evidence-based adult studies, the extrapolation to the paediatric patient remains unvalidated. Objective: The purpose of this study was to compare treatment according to ACCM/PALS guidelines, performed with and without ScvO(2) goal-directed therapy, on the morbidity and mortality rate of children with severe sepsis and septic shock. Design, participants and interventions: Children and adolescents with severe sepsis or fluid-refractory septic shock were randomly assigned to ACCM/PALS with or without ScvO(2) goal-directed resuscitation. Measurements: Twenty-eight-day mortality was the primary endpoint. Results: Of the 102 enrolled patients, 51 received ACCM/PALS with ScvO(2) goal-directed therapy and 51 received ACCM/PALS without ScvO(2) goal-directed therapy. ScvO(2) goal-directed therapy resulted in less mortality ( 28-day mortality 11.8% vs. 39.2%, p = 0.002), and fewer new organ dysfunctions ( p = 0.03). ScvO(2) goal-directed therapy resulted in more crystalloid ( 28 ( 20-40) vs. 5 ( 0-20) ml/kg, p < 0.0001), blood transfusion ( 45.1% vs. 15.7%, p = 0.002) and inotropic ( 29.4% vs. 7.8%, p = 0.01) support in the first 6 h. Conclusions: This study supports the current ACCM/PALS guidelines. Goal-directed therapy using the endpoint of a ScvO(2) = 70% has a significant and additive impact on the outcome of children and adolescents with septic shock.

Understanding the genetic diversity, spatial genetic structure and mating system at the hierarchical levels of fruits and individuals of a continuous Theobroma cacao population from the Brazilian Amazon

Understanding the mating patterns of populations of tree species is a key component of ex situ genetic conservation. In this study, we analysed the genetic diversity, spatial genetic structure (SGS) and mating system at the hierarchical levels of fruits and individuals as well as pollen dispersal patterns in a continuous population of Theobroma cacao in Para State, Brazil. A total of 156 individuals in a 0.56 ha plot were mapped and genotyped for nine microsatellite loci. For the mating system analyses, 50 seeds were collected from nine seed trees by sampling five fruits per tree (10 seeds per fruit). Among the 156 individuals, 127 had unique multilocus genotypes, and the remaining were clones. The population was spatially aggregated; it demonstrated a significant SGS up to 15m that could be attributed primarily to the presence of clones. However, the short seed dispersal distance also contributed to this pattern. Population matings occurred mainly via outcrossing, but selfing was observed in some seed trees, which indicated the presence of individual variation for self-incompatibility. The matings were also correlated, especially within ((r) over cap (p(m)) = 0.607) rather than among the fruits ((r) over cap (p(m)) = 0.099), which suggested that a small number of pollen donors fertilised each fruit. The paternity analysis suggested a high proportion of pollen migration (61.3%), although within the plot, most of the pollen dispersal encompassed short distances (28m). The determination of these novel parameters provides the fundamental information required to establish long-term ex situ conservation strategies for this important tropical species. Heredity (2011) 106, 973-985; doi:10.1038/hdy.2010.145; published online 8 December 2010

A decision support system to facilitate management of patients with acute gastrointestinal bleeding

Objective: To develop a model to predict the bleeding source and identify the cohort amongst patients with acute gastrointestinal bleeding (GIB) who require urgent intervention, including endoscopy. Patients with acute GIB, an unpredictable event, are most commonly evaluated and managed by non-gastroenterologists. Rapid and consistently reliable risk stratification of patients with acute GIB for urgent endoscopy may potentially improve outcomes amongst such patients by targeting scarce health-care resources to those who need it the most. Design and methods: Using ICD-9 codes for acute GIB, 189 patients with acute GIB and all. available data variables required to develop and test models were identified from a hospital medical records database. Data on 122 patients was utilized for development of the model and on 67 patients utilized to perform comparative analysis of the models. Clinical data such as presenting signs and symptoms, demographic data, presence of co-morbidities, laboratory data and corresponding endoscopic diagnosis and outcomes were collected. Clinical data and endoscopic diagnosis collected for each patient was utilized to retrospectively ascertain optimal management for each patient. Clinical presentations and corresponding treatment was utilized as training examples. Eight mathematical models including artificial neural network (ANN), support vector machine (SVM), k-nearest neighbor, linear discriminant analysis (LDA), shrunken centroid (SC), random forest (RF), logistic regression, and boosting were trained and tested. The performance of these models was compared using standard statistical analysis and ROC curves. Results: Overall the random forest model best predicted the source, need for resuscitation, and disposition with accuracies of approximately 80% or higher (accuracy for endoscopy was greater than 75%). The area under ROC curve for RF was greater than 0.85, indicating excellent performance by the random forest model Conclusion: While most mathematical models are effective as a decision support system for evaluation and management of patients with acute GIB, in our testing, the RF model consistently demonstrated the best performance. Amongst patients presenting with acute GIB, mathematical models may facilitate the identification of the source of GIB, need for intervention and allow optimization of care and healthcare resource allocation; these however require further validation. (c) 2007 Elsevier B.V. All rights reserved.

Activation of the shoulder and arm muscles during axial load exercises on a stable base of support and on a medicine ball

The purpose of this study was to compare SEMG activities during axial load exercises on a stable base of support and on a medicine ball (relatively unstable). Twelve healthy male volunteers were tested (x = 23 +/- 7y). Surface EMG was recorded from the biceps brachii, anterior deltoid, clavicular portion of pectoralis major, upper trapezius and serratus anterior using surface differential electrodes. All SEMG data are reported as percentage of RMS mean values obtained in maximal voluntary contractions for each muscle studied. A 3-way within factor repeated measures analysis of variance was performed to compare RMS normalized values. The RMS normalized values of the deltoid were always greater during the exercises performed on a medicine ball in relation to those performed on a stable base of support. The trapezius showed greater mean electric activation amplitude values on the wall-press exercise on a medicine ball, and the pectoralis major on the push-up. The serratus and biceps did not show significant differences of electric activation amplitude in relation to both tested bases of support. Independent of the base of support, none of the studied muscles showed significant differences of electric activation amplitude during the bench-press exercise. The results contribute to the identification of the levels of muscular activation amplitude during exercises that are common in clinical practice of rehabilitation of the shoulder and the differences in terms of type of base of support used. (C) 2006 Elsevier Ltd. All rights reserved.

Structure activity relationship, acute toxicity and cytotoxicity of antimycobacterial neolignan analogues

Objectives The study`s aims were to evaluate the antimycobacterial activity of 13 synthetic neolignan analogues and to perform structure activity relationship analysis (SAR). The cytotoxicity of the compound 2-phenoxy-1-phenylethanone (LS-2, 1) in mammalian cells, such as the acute toxicity in mice, was also evaluated. Methods The extra and intracellular antimycobacterial activity was evaluated on Mycobacterium tuberculosis H37Rv. Cytotoxicity studies were performed using V79 cells, J774 macrophages and rat hepatocytes. Additionally, the in-vivo acute toxicity was tested in mice. The SAR analysis was performed by Principal Component Analysis (PCA). Key findings Among the 13 analogues tested, LS-2 (1) was the most effective, showing promising antimycobacterial activity and very low cytotoxicity in V79 cells and in J774 macrophages, while no toxicity was observed in rat hepatocytes. The selectivity index (SI) of LS-2 (1) was 91 and the calculated LD50 was 1870 mg/kg, highlighting the very low toxicity in mice. SAR analysis showed that the highest electrophilicity and the lowest molar volume are physical-chemical characteristics important for the antimycobacterial activity of the LS-2 (1). Conclusions LS-2 (1) showed promising antimycobacterial activity and very weak cytotoxicity in cell culture, as well as an absence of toxicity in primary culture of hepatocytes. In the acute toxicity study there was an indication of absence of toxicity on murine models, in vivo.

Gangliosides Are Important for the Preservation of the Structure and Organization of RBL-2H3 Mast Cells

Gangliosides are known to be important in many biological processes. However, details concerning the exact function of these glycosphingolipids in cell physiology are poorly understood. in this study, the role of gangliosides present on the surface of rodent mast cells in maintaining cell structure was examined using RBL-2H3 mast cells and two mutant cell lines (E5 and D1) deficient in the gangliosides, GM(1) and the alpha-galactosyl derivatives of the ganglioside GD(1b). The two deficient cell lines were morphologically different from each other as well as from the parental RBL-2H3 cells. Actin filaments in RBL-2H3 and E5 cells were under the plasma membrane following the spindle shape of the cells, whereas in D1 cells, they were concentrated in large membrane ruffles. Microtubules in RBL-2H3 and E5 cells radiated from the centrosome and were organized into long, straight bundles. The bundles in D1 cells were thicker and organized circumferentially under the plasma membrane. The endoplasmic reticulum, the Golgi complex, and the secretory granule matrix were also altered in the mutant cell lines. These results suggest that the mast cell-specific alpha-galactosyl derivatives of ganglioside GD(1b) and GM(1) are important in maintaining normal cell morphology. (J Histochern Cytochem 58:83-93, 2010)