Pancreatic cancer is a rare tumor with an extremely low survival rate. Its known risk factors include the chronic use of tobacco and excessive alcohol consumption and the presence of chronic inflammatory diseases, such as pancreatitis and type 2 diabetes. Angiogenesis and lymphangiogenesis, which have been the focus of recent research, are considered prognostic factors for cancer development. Knowing the angiogenic and lymphangiogenic profiles of a tumor may provide new insights for designing treatments according to the different properties of the tumor. The aim of this study was to evaluate the density of blood and lymphatic vessels, and the expression of VEGF-A, in pancreatic adenocarcinomas, as well as the relationship between blood and lymphatic vascular density and the prognostically important clinical-pathological features of pancreatic tumors.Paraffin blocks containing tumor samples from 100 patients who were diagnosed with pancreatic cancer between 1990 and 2010 were used to construct a tissue microarray. VEGF expression was assessed in these samples by immunohistochemistry. To assess the lymphatic and vascular properties of the tumors, 63 cases that contained sufficient material were sectioned routinely. The sections were then stained with the D2-40 antibody to identify the lymphatic vessels and with a CD34 antibody to identify the blood vessels. The vessels were counted individually with the Leica Application Suite v4 program. All statistical analyses were performed using SPSS 18.0  software, and p values ≤ 0.05 were considered significant.In the Cox regression analysis, advanced age (p=0.03) and a history of type 2 diabetes (p=0.014) or chronic pancreatitis (p=0.02) were shown to be prognostic factors for pancreatic cancer. Blood vessel density (BVD) had no relationship with clinical-pathological features or death. Lymphatic vessel density (LVD) was inversely correlated with death (p=0.002), and by Kaplan-Meyer survival analysis, we found a significant association between low LVD (p=0.021), VEGF expression (p=0.023) and low patient survival.Pancreatic carcinogenesis is related to a history of chronic inflammatory processes, such as type 2 diabetes and chronic pancreatitis. In pancreatic cancer development, lymphangiogenesis can be considered an early event that enables the dissemination of metastases. VEGF expression and low LVD can be considered as poor prognostic factors as tumors with this profile are fast growing and highly aggressive.http://www.diagnosticpathology.diagnomx.eu/vs/5113892881028514The virtual slide(s) for this article can be found here:  Pancreatic cancer is a rare tumor, according to the World Health Organization (WHO). The survival rate of patients is extremely low, and as such, it is considered as one of the most aggressive tumor types .There are two types of cells in the pancreas, the exocrine cells and endocrine cells. The most common pancreatic tumors are originated from exocrine  cells and trerefore are classified as adenocarcinomas. The adenocarcinomas account for up to 90% of pancreatic cancer cases. Pancreatic adenocarcinoma is considered rare before the age of 30 years and becomes more common after the age of 60 years.The use of tobacco and its derivatives is considered the main risk factor for pancreatic cancer development as it increases the chance of pancreatic cancer development by three times compared with non-smokers. Other risk factors include the excessive consumption of alcoholic beverages, meat and fat and the presence of some diseases, such as chronic pancreatitis or type 2 diabetes (DM 2), as well as a family history of cancer .Angiogenesis is considered as one of the most important factors for tumor development and progression. However, this process is also physiologically important . LymphanDuring the neoplastic process, angiogenesis supplies nutrients to the primary tumor. At a later stage, the newly formed vessels provide routes for tumor cells to migrate, thus leading to metastasis in a process referred to as hematogenous spread. However, the dissemination of tumor cells via the lymphatic system is regarded as the main factor for the development of metastases in the regional lymph nodes and other distant organs ,9.In this way, both angiogenesis and lymphangiogenesis are considered important in cancer development. Knowing the angiogenic and lymphangiogenic profiles of a tumor may provide new insights that may enable targeted treatments according to tumor behavior ,3,10,11.The aim of this study was to evaluate the density of blood and lymphatic vessels, and the expression of VEGF-A, in pancreatic adenocarcinomas, as well as the relationship between blood and lymphatic vessel density (BVD and LVD) and the prognostically important clinical-pathological factors in pancreatic tumors.In June 2012 we requested the medical records containing the clinical data of patients with pancreatic cancer diagnosed between 1990 and 2010 from the Medical Archive Service of our Institution. The samples had been collected from January 1990 to December 2010. The sampling procedure applied for diagnostic purpose was in accordance with current literature [In the assessment of medical records, we obtained information concerning clinical data, such as age, gender and self-reported ethnicity. The following data were also retrieved: involvement of lymph nodes, presence of metastasis, disease-specific survival (DSS) and death. Factors that have been previously reported to contribute to the development of pancreatic cancer, such as DM 2, chronic pancreatitis and tobacco or alcohol consumption were also evaluated. Patients with insufficient clinical data from the medical records were excluded from the study.The slides of these patients were retrieved from the Pathologic Service, and a pathologist (ARS) confirmed the diagnosis of pancreatic cancer, as well as the histological grade of the tumors.One hundred patients who had sufficient clinical data and a sufficient amount of tumor sample in the paraffin blocks were included in the study.The study was carried out in accordance with the 1975 Declaration of Helsinki and was approved by the local research ethics committee .2 cylindrical areas that corresponded to the most representative area of each lesion were removed from the paraffin blocks and transferred to a receiver block using a Manual Tissue Arrayer I .For the selection of tissues to be included in the TMA block, archived slides that were previously stained with hematoxylin and eosin were examined. All TMA processing was carried out in the Department of Pathologic Anatomy of A. C. Camargo Cancer Center . Next, 1.1 mmEach cylinder on the TMA slide represented one patient. From the TMA block, 3-μm histological sections were cut using a conventional rotary microtome  and transferred to a TMA slide using the paraffin tape-transfer system , according to manufacturer's instructions.All samples retrieved had been fixed in 4% neutral formalin and embedded in paraffin. Of the 100 selected cases, only 63 contained sufficient material for traditional sectioning and counting of the blood and lymphatic vessels. The IHC reactions were developed using Reveal HRP (Spring – Code SPD-125). The paraffin sections were de-waxed in xylene and rehydrated through a series of graded alcohols. The sections were placed in 10 mM citrate buffer (pH 6) and were subjected to heat retrieval using a vapor lock for 30 minutes.After antigen retrieval, the samples were allowed to cool for 15 minutes at room temperature. Endogenous peroxidase activity and proteins were blocked according to the manufacturer's protocol. The specimens were incubated at 4°C overnight with the following primary antibodies: D2-40 (Lymphatic Marker)  for microvascular lymphatic counting, Endothelial Cell Marker (CD34)  for blood vessels counting and VEGF , which recognizes the isoforms with splicing at the 121, 165 and 189 amino acids.After the incubation with primary antibody, the slides were incubated with the visualization system and then with the chromogen substrate, liquid diaminobenzidine (DAB). The slides were then stained with hematoxylin, dehydrated in a series of alcohols and permanently mounted with Permount polymer . Negative controls were prepared by the omission of the primary antibody.We used a 10% cut off for the quantitative analysis of VEGF-positive neoplasic cells. As such, samples were considered positive when 10% or more cells showed cytoplasmatic VEGF expression, and samples were considered negatives if VEGF expression was absent or present in less than 10% of cells ,14.The blood and lymphatic vessel density was analyzed according to Lin et al.  and WeidThe statistical analysis of the relationship between the pathological and clinical data and the immunohistochemical results was performed by Fisher’s exact test and Chi-square test. Univariate analysis was conducted by the Kaplan-Meier method and Cox’s multiple regression was used for multivariate analysis. For both the clinical and pathological analyses and survival analysis, p<0. We 05 was considered statistically significant. All statistical analysis was performed using SPSS 18.0  software.Of the paraffin blocks obtained from the Pathology Service, we excluded cases that did not have enough material for immunohistochemical reactions and/or for BVD and LVD counting or those for which the clinical information necessary for the research was not available. As such, this study was comprised of 100 cases for VEGF expression analysis by TMA and for epidemiologic study  and 63 cases for the BVD and LVD analysis.Of these 100 cases, 52% were men and 48% were women. With respect to self-reported ethnicity, 80% of the patients declared themselves white, 15.3% mixed race and 4.6% black. The ages at diagnosis ranged from 37 to 95 years . The median survival of this research population was 9.5 months, 67.6% of the patients had metastases, and 84.6% had died by the end date of the records search. Only 3.17% of patients had more than 4-year disease-specific survival.In the Cox regression analysis, the BVD and LVD did not have independent prognostic value for pancreatic cancer . Among the data analyzed, only age (p=0.03), DM 2 (p=0.014) and chronic pancreatitis history (p=0.02) were statistically significant , while BVD had no significant relationship with death events . Using the Kaplan-Meyer survival analysis with log-rank test, we found a significant association between low LVD and low patient survival (p=0.021) Figure  and betwIn our work we include only adenocarcinomas because they are far more comum than the pancreatic tumors of endocrine origins. However, it is worthwhile say that pancreatic tumors of endocrine origin are less aggressive than carcinomas, with distinct prognostic parameters . The epiAccording to previous studies, men are more likely to develop pancreatic cancer, and the difference between the genders is higher in developed countries than in developing countries. The same trend was found in our study, in which 52% of the patients were men and 48% were women. Although pancreatic cancer is not among the ten most common cancers, its incidence tends to increase over time. In developing countries, this is mainly due to two primary reasons, increased life expectancy and the adoption of risk behavior, including high calorie and fatty food intake and consumption of tobacco and alcoholic beverages, at early ages ,20.Klöppel et al.  reportedWith respect to self-declared ethnicity, 80% of the patients declared themselves white, 15.3% intermediate and 4.6% black. This is in contrast to other studies that have highlighted the black “race” as a risk factor for the pancreatic cancer development ,20. HoweBy multivariate analysis of the clinical-pathological data, we identified some independent prognostic factors for pancreatic cancer. An age higher than 74 years was an independent factor (p=0.03) because the higher the age of the individual, the greater the chance of developing neoplasms. The risk with respect to old age is already well known due to the duration allowing for the accumulation of mutations in the cells, mainly in the pool of stem cells, which multiply slowly. Over time, these cells acquire the necessary mutations to maintain a balance between them and the organ microenvironment . AnotherSeveral studies have been conducted to clarify the relationship between DM 2, chronic pancreatitis and the risk of developing pancreatic cancer. Prizment et al.  showed tThe vascularization is considered an important step for tumor progression , so it iThe relationship between LVD and tumor behavior is controversial and has only been recently reported in the literature. Sleeman and Thiele  establisIn pancreatic endocrine tumors, Rubbia-Brandt et al.  found a Because we observed an inverse relationship between LVD and survival, we hypothesized that low LVD is due to the accelerated growth of the tumor and the eventual loss of function of the lymphatic vessels that were present. Accordingly, tumors with low LVD are more likely to be fast growing and of a more advanced stage, which would explain the low survival rate of these patients. The function of these vessels could have been lost because of the internal pressure caused by rapid tumor growth, which would lead to the collapse of the vessels, the invasion of tumor cells in the lymph vessels or other mechanisms that have yet to be elucidated . Some stIn agreement with the research by Yin et al. , which dOf the 100 pancreatic tumor cases that were used to construct the TMA and subsequently analyzed by immunohistochemistry for VEGF expression, 71% showed cytoplasmic VEGF expression. By Kaplan-Meyer survival curve analysis, the expression of VEGF in tumors proved to be significantly associated (p=0.023) with poor prognosis and a reduction in patient survival time.It is known that the VEGF family of proteins contributes to the development of new blood vessels through the process of angiogenesis, which was widely studied and discussed by Folkman and reviewed by other researchers. Angiogenesis leads to the spread of tumor cells by hematogenous routes and, consequently, to metastasis -42. The The family of VEGFs is composed of VEGF-A, VEGF-B, VEGF-C, VEGF-D, VEGF-E, VEGF-F, and placental growth factor (PlGF). VEGF-A was the first to be discovered and, therefore, was originally named VEGF. This factor was directly linked to angiogenesis that occurs in physiological processes, such as embryonic development, and in pathological processes, which include inflammation, wound healing and tumor growth. The function of VEGF-B, which is expressed in skeletal and cardiac muscle and brown adipose tissue, is not understood. However, unlike VEGF-A, its expression is not stimulated by low temperatures or by hypoxia. VEGF-C and-D are linked to lymphangiogenesis and, unlike VEGF-A, are only expressed in lymphatic endothelial cells in physiological situations. The most recently discovered factors are VEGF-E, which is encoded by a virus, and VEGF-F, which is expressed in the venom of a snake .In our research, we used a VEGF antibody that, according to the manufacturer, has affinity for the protein isoforms with splicing in amino acids 121, 165 and 189, which correspond to VEGF-A ,45. The The independent prognostic factors identified in our study, advanced age and a history of DM 2 or chronic pancreatitis, are supported by the relationship between inflammation and the increased expression of VEGF. During inflammatory diseases, the chronic high concentrations of insulin, ROS, cytokines and inflammatory mediators, such as TNF-α and COX-2, lead to an increase the expression of pro-angiogenic factors, the most important being VEGF-A ,24.Even though VEGF-A is directly linked to angiogenesis, recent studies have shown that this factor is also involved in lymphangiogenesis during tumor development. The biological effects of the VEGF family members occur through the interaction of the factors, which are secreted by tumor cells or matrix inflammatory cells, with transmembrane receptors located in the vascular and lymphatic endothelial cells. The interaction of the ligand with receptor leads to dimerization and the autophosphorylation of the receptor intracellular domains that, in turn, generates a cascade of reactions involving proteins related to cellular survival and division. VEGF-A can interact with the receptors VEGFR-1, VEGFR-2 and the neuropilins 1 and 2. However, it is through interaction with the VEGFR-2, found specifically in lymphatic endothelial cells, that lymphangiogenesis is induced .VEGF-A can promote lymphangiogenesis either indirectly or directly. Indirectly, it can recruit inflammatory cells that, in turn, will produce VEGF-C and VEGF-D, which are known to promote lymphangiogenesis. Directly, VEGF-A will interact with its receptor, VEGFR-2, which is present in pre-existing lymphatic vessels, activating them . AccordiVEGF expression is increased both at the transcription and translation levels in pancreatic tumor tissues, compared to surrounding non-tumoral tissue. Its expression, according to Liang et al. , is relaIn our study, we demonstrated that the LVD is inversely related to survival, while the expression of VEGF-A is directly related to survival. In accordance with the current literature, we postulate that the expression of VEGF-A is an early event in the development of cancer. Inflammatory processes, which are known to increase the likelihood of cancer development, also promote the overexpression of VEGF-A ,25,48. TWe conclude that advanced age and a history of type 2 diabetes mellitus or chronic pancreatitis are independent prognostic factors for the development of pancreatic cancer. We also conclude that the expression of VEGF-A and low LVD may contribute significantly to poor prognosis because of increased tumor aggressiveness and low patient survival. We add new evidences in literature that lymphatic vessel density is related to survival in patients with pancreatic carcinoma and is relationship with VEGF-A expression may be important for future therapeutic strategies.WHO: World Health Organization; INCA: Instituto Nacional do Câncer; DM2: Diabetes mellitus type 2; VEGFs: Vascular endothelial growth factors; DSS: Disease specific survival; TMA: Tissue microarray; IHC: Immunohistochemistry; BVD: Blood vessel density; LVD: Lymphatic vessel density; DNA: Deoxyribonucleic acid; PlGF: Placenta growth factor; TNF-α: Tumoral necrose factor-α; COX-2: Cyclooxygenase-2; VEGFR: Vascular endothelial growth factor receptor; ROS: Reactive oxygen species.The authors declare that they have no competing interests.VAZ: design and intellectual content definition, data acquisition and analysis and preparation of the manuscript. GGS: design and intellectual content definition, data analysis and critical review of the manuscript. JPOC: statistical analysis. DFS: critical review of the manuscript. FAS: coordination of TMA slide preparation. ARS: anatomopathologic examination of the samples, research coordination and critical review of the final manuscript. All authors read and approved the final manuscript.


This study aimed to evaluate comorbidity for MD in a large ED sample and both personality and anger as clinical characteristics of patients with ED and MD. We assessed 838 ED patients with psychiatric evaluations and psychometric questionnaires: Temperament and Character Inventory, Eating Disorder Inventory-2, Beck Depression Inventory, and State-Trait Anger Expression Inventory. 19.5% of ED patients were found to suffer from comorbid MD and 48.7% reported clinically significant depressive symptomatology: patients with Anorexia Binge-Purging and Bulimia Nervosa were more likely to be diagnosed with MD. Irritable mood was found in the 73% of patients with MD. High Harm Avoidance (HA) and low Self-Directedness (SD) predicted MD independently of severity of the ED symptomatology, several clinical variables, and ED diagnosis. Assessing both personality and depressive symptoms could be useful to provide effective treatments. Longitudinal studies are needed to investigate the pathogenetic role of HA and SD for ED and MD. Lifetime comorbidity between Eating Disorders (EDs) and Mood Disorders has been confirmed by several retrospective studies reporting that in Anorexia Nervosa (AN) the prevalence of mood disorders varies between 64.1% and 96% whereas in Bulimia Nervosa (BN) between 50% and 90%. In addition, a substantial part of individuals affected by an ED is likely to be affected also by a mood disorder, and the current comorbidity varies from 12.7 to 68% in AN and is about 40% in BN [In spite of the importance of this topic, most of previous studies on mood in ED were conducted on small samples , and the role of age, duration of illness, and weight were not considered. Moreover, ED subtypes and their differences were not carefully classified, particularly Eating Disorder Not Otherwise Specified (EDNOS) , and theIndeed anxious/preoccupied behaviors, mood intolerance, and dysthymic traits have been reported in ED patients , 9, 10. With this study we aimed to (a) evaluate the prevalence of a current MD in a large sample of ED patients; (b) assess the prevalence of MD with irritable mood in ED patients; (c) provide data supporting the correlation between MD and ED severity; (d) show possible differences between ED patients with and without MD, independently from the severity of eating symptomatology.n = 214; AN, binge-purging type (AN-BP), n = 103; BN, purging type (BN-E), n = 223, Eating Disorder Not Otherwise Specified (EDNOS), n = 298. Patients with BN, nonpurging type, were excluded because their number (n = 13) was not statistically relevant. Diagnoses of ED and MD were based on the structured clinical interview for DSM-IV (SCID-I) [The sample consisted of 838 patients admitted to the outpatient service of the ED Program of the University of Turin between the 1st of January 2003 and the 31st of December 2010. All subjects were diagnosed with an ED, and the sample was represented by the following subjects: AN, restricting type (AN-R), (SCID-I) . ExclusiThe first two assessment interviews were conducted by psychiatrists experienced in the diagnosis and treatment of ED. Irritable mood and angry outbursts were assessed according to the criteria proposed by Fava and Kellner  and evalThe TCI  is dividThe 44-item STAXI  measuresThe BDI  is a selThe EDI-2  is a selt-test. Age, age of onset of the disorder, duration of illness, and Body Mass Index (BMI) were analysed in terms of confounding variables using a Univariate General Linear Model.Statistical analyses were carried out using Statistical Package for Social Sciences (SPSS) software version 13.0 for Windows . Categorical data were compared using the chi-squared test, and continuous data were analysed using a two-tailed independent A logistic regression analysis was performed to detect personality variables that independently relate with MD. The presence/absence of MD was regarded as a dependent variable. ED diagnosis, duration of illness expressed in months, BMI, age, age of onset of the disorder, presence/absence of irritable mood, and scores on the TCI, EDI-2, and STAXI scales were included as independent variables. To assess the possible correlation with the depressive state of personality traits we found as significant at the linear regression has been checked the linear correlation (Pearson bivariate) between BDI and personality score and we performed also a MANOVA with personality scores as dependent variables, depressive versus nondepressive group as fixed factor, the BDI score as covariate, an the BDI group interaction.Sociodemographic and clinical features are reported in Tables n = 161) of the sample: 15.3% of AN-R (n = 33), 25.5% of AN-BP (n = 25), 25.3% of BN (N = 56), and 16% of EDNOS (n = 47). Significant differences were found among AN and EDNOS individuals and the other ED subtypes .Subjects with MD represent the 19.5% , after controlling for age, age of onset of the disorder, duration of illness, and BMI. Patients with MD did not show any significant difference when compared to those without MD in regard to age, age of onset of the disorder, duration of illness, and BMI see . The BDIχ2 = 9.3859; P = 0.02). Considering both the 48.7% of the sample with a BDI score >10 and the 19.5% of MD patients the total percentage of patients with relevant depressive symptomatology is 68.2%.The BDI scores of 408 patients (48.7% of the sample) who were not diagnosed with MD were higher than 10 and so clinically significant; there were statistically significant differences among diagnostic subtypes in this regard . Moreover, subjects with MD obtained more pathological scores on all STAXI subscales, even after controlling for age, age of onset of the disorder, duration of illness, and BMI, than did patients without MD diagnosis . The state anger STAXI subscale , the HA subscale of the TCI , the SD subscale of the TCI , and Ineffectiveness as measured by the EDI-2  independently correlated with MD. Age, age of onset, ED diagnosis, BMI, episodes of binge-eating and vomiting per week, irritable mood, and other variables measured by the STAXI, TCI, and EDI-2 were not significant.The logistic regression model was significant  and inversely with . Using the MANOVA, HA, and SD differences remain significant even when controlled for BDI scores and for the interaction BDI group . Also the BDI score effect was found significant for both variables (both variables: P < 0.001).BDI scores correlate significantly directly with HA  were more likely to be diagnosed with MD when compared to AN and EDNOS. This association is supported by previous researches showing that individuals with purging symptomatology are more likely to show comorbid disorders and greater clinical severity , 31. AlsMoreover, in our sample MD in ED patients seem typically characterized by irritable mood as measured according to Fava and Kellner criteria . To our Considering the BDI, the 48.7% of the sample obtained scores indicating a clinically significant depressive symptomatology (BDI > 10); this datum should be added to the 19.5% of individuals affected by full MD and therefore the total percentage of individuals with relevant depressive symptoms was 68.2%. Moreover, patients with ED were reported to suffer from a wide spectrum of depressive symptoms . SpecifiMoreover, also this lager group of depressed patients reported at the STAXI higher scores than ED patients without depressive symptoms. Therefore, previous considerations regarding the group with both ED and DM about high percentage of irritable mood can be extended to depressed patients without an ED.We found that eating psychopathology, as measured by the EDI-2 scales included in this study, was significantly more severe in patients with comorbid ED and MD than in patients with ED without MD. This correlation between a severe depressive symptomatology and ED severity validated the results of previous studies and confirmed expected hypothesis , 30. MorThe presence of MD represented an index of clinical severity and/or an indication of the acuity of the ED. Therefore, diagnostic evaluation for MD in patients suffering from AN or BN should be considered, and psychotherapeutic involvement in treatment planning should be included as appropriate, also because these patients are often hopeless about the possibility of change and this should be carefully considered in treatments . Indeed,The logistic regression analysis showed that the Ineffectiveness subscale of EDI-2 independently predicted MD in the sample. Low self-esteem represents the common core symptom of ED and depression. Thus it could be hypothesized that ED treatments based on cognitive-behavioral therapies focused on low self-esteem  can be eAntidepressants might be effective for treating comorbid ED and depression . HoweverPatients with both ED and MD were characterized by higher HA and lower scores on the RD, SD, and C scales of the TCI. Logistic regression showed that Harm Avoidance and Self-Directedness remained significant after controlling for personal and several clinical variables. These data are consistent with the results of previous studies that have identified these traits as characterizing ED samples when compared to healthy controls . Other sThis study showed that higher HA and low SD scores were correlated with comorbid MD in ED patients; this correlation was found to be independent of the severity of the ED , age, age of onset, and duration of illness. Other studies have shown that low SD can predict suicide attempts among ED subjects , 54.ED patients with a personality profile characterized by high HA and low RD, SD, and C represent a subgroup of patients likely to experience feelings of inferiority, inadequacy, unhappiness, anxiety, and dependence , 55–57. The cross-sectional design of this study makes it difficult to rule out the possibility that high HA scores represented a risk factor or a “scarring effect” for ED and depression on personality , 59. OthThis study is limited by the lack of a control group of healthy subjects or of another clinical population, including patients with other comorbid disorders, and by not considering lifetime comorbidity. On the other hand, one strength of this study is the large sample of patients with MD and ED.This study aimed to evaluate comorbidity between ED and MD and the role of personality as predictor of MD in ED. Our data are in line with previous literature since we found a current prevalence of MD of 19.5% with significant differences among diagnostic subtypes since patients with purging behaviours were more likely to be affected by MD. Irritability was found to be a feature of MD in ED with rates of irritability and angry outbursts twice as prevalent among patients with MD and ED (73%) than among depressed patients without ED as reported in the literature. Considering the BDI, the 48.7% of the sample obtained scores indicating a clinically significant depressive symptomatology (BDI > 10). The eating psychopathology, as measured by the EDI-2 scales, was significantly more severe in patients with MD comorbidity. With regard to personality dimensions, patients with ED and MD showed higher Harm Avoidance and lower scores on the Reward Dependence, Self-Directedness, and Cooperativeness scales of the TCI. The personality dimensions of high HA and low SD could be risk factors in the development of Major Depression in ED individuals because the differences between depressed and non-depressed groups remain significant even after controlling for the BDI score and BDI group interaction.Clinicians should carefully evaluate in patients with Eating Disorders their depressive symptomatology and the role of anger and personality to provide effective treatments tailored to person and not based only on symptomatology .


The genetic parameters for growth, reproductive and maternal traits in a multibreed meat sheep population were estimated by applying the Average Information Restricted Maximum Likelihood method to an animal model. Data from a flock supported by the Programa de Melhoramento Genético de Caprinos e Ovinos de Corte (GENECOC) were used. The traits studied included birth weight (BW), weaning weight (WW), slaughter weight (SW), yearling weight (YW), weight gain from birth to weaning (GBW), weight gain from weaning to slaughter (GWS), weight gain from weaning to yearling (GWY), age at first lambing (AFL), lambing interval (LI), gestation length (GL), lambing date (LD - number of days between the start of breeding season and lambing), litter weight at birth (LWB) and litter weight at weaning (LWW). The direct heritabilities were 0.35, 0.81, 0.65, 0.49, 0.20, 0.15 and 0.39 for BW, WW, SW, YW, GBW, GWS and GWY, respectively, and 0.04, 0.06, 0.10, 0.05, 0.15 and 0.11 for AFL, LI, GL, LD, LWB and LWW, respectively. Positive genetic correlations were observed among body weights. In contrast, there was a negative genetic correlation between GBW and GWS (-0.49) and GBW and GWY (-0.56). Positive genetic correlations were observed between AFL and LI, LI and GL, and LWB and LWW. These results indicate a strong maternal influence in this herd and the presence of sufficient genetic variation to allow mass selection for growth traits. Additive effects were of little importance for reproductive traits, and other strategies are necessary to improve the performance of these animals. The Brazilian meat sheep industry has expanded in recent years mainly through an increase in the number of farmers. However, performance indexes are lower than those required to guarantee efficiency and competitiveness compared with other animal sectors. Correct selection is one of the most important strategies to maximize production in animal breeding. However, the lack of estimates for the genetic parameters necessary to predict genetic gains is commonly cited as an obstacle in the design and implementation of conservation-based selective breeding programs in the tropics. As a result, there are few reports on successful selective breeding programs in this region  and SarmAccording to The lack of systematic record keeping by Brazilian sheep breeders means that there have been few studies of the genetic parameters related to reproductive and maternal traits in the Brazilian flock. This lack of information greatly hinders adequate development of the meat sheep industry in which the reproductive and maternal efficiencies of ewes must be constantly evaluated in order to ensure profitable production. The aim of this study was therefore to estimate the additive genetic parameters for growth, reproductive and maternal traits in meat sheep of a multibreed population raised in Brazil.The data bank analyzed contained 12 years (1996-2007) of information from a flock maintained by Gaasa Agropecuária Ltda. and supported by the Programa de Melhoramento Genético de Caprinos e Ovinos de Corte (GENECOC) of Embrapa Caprinos e Ovinos. This herd is located at Inhumas in the state of Goiás  with a tropical semi-humid climate.®  at 50 and 80 days of age; all of the animals were vaccinated annually in March. Treatment for eimeriosis was done twice a year (March and October). Fecal egg counts and the Famacha method were used to control gastrointestinal nematodes. Footbaths  were used during the rainy season.The sheep underwent standard sanitary care and were vaccinated with Poli-StarThe breeding season was year round with ewes grouped by lots. The lambs were weaned at 60 days, confined, and fed with maize silage and corn and soy bran meal containing 21% crude protein (CP); they were slaughtered at 120-150 days. After weaning the lambs, the ewes underwent a 30-day breeding season in the presence of vasectomized rams. Ewes and rams were fed with Tifton 85 pasture, silage and meal containing 15% CP.To understand the flock formation, initially purebred Santa Inês, Poll Dorset, Hampshire Down, Suffolk, Île de France, Brazilian Somali and Texel rams were acquired with Santa Inês, Poll Dorset, Morada Nova, Brazilian Somali, Santa Inês x Morada Nova and Santa Inês x Brazilian Somali dams. Later, purebred Dorper, Primera and East Friesian rams were acquired. The matings were controlled but not designed. All rams of all breeds had the same opportunity to mate ewes of all genetic groups (purebred and crossbred). As a result, within a few years the flock was a mixture of crossbred dams with a varied contribution from the different breeds. Only the rams and some Santa Inês, Poll Dorset and Brazilian Somali dams were purebred.Data used in this study were obtained several years after formation of the flock, and already contained of the all breeds indicated above. However, many genetic groups were excluded from analysis because of insufficient information. The rams used included purebred Santa Inês (36), Poll Dorset (16), Hampshire Down (5), East Friesian (4), Dorper (4), Suffolk (3), Île de France (2), Brazilian Somali (2), Texel (1) and Primera (1). The dams used included purebred Santa Inês, Poll Dorset, Brazilian Somali and crossbreeds involving all of the breeds indicated above. The growth traits analyzed included birth weight (BW), weaning weight (WW), slaughter weight (SW), yearling weight (YW), weight gain from birth to weaning (GBW), weight gain from weaning to slaughter (GWS) and weight gain from weaning to yearling (GWY). The WW of lambs > 30 days old but weighing < 5 kg were excluded. Likewise, the SW of animals with a slaughter age > 365 days were also excluded. All weights from animals 330-395 days old were considered as YW. The YW of lambs > 20 kg were excluded.The reproductive and maternal traits analyzed included age at first lambing (AFL), lambing interval (LI), gestation length (GL), lambing date , litter weight at birth (LWB) and litter weight at weaning (LWW). Data for animals with an AFL > 800 days and an LI > 550 days were excluded. Lambing orders from 1 to 8 were analyzed.The MIXED procedure of SAS  was used to define fixed effects in the analysis. For each trait, many linear models were evaluated, with the use of contemporary groups or effects being analyzed individually. The logarithm of the Restricted Maximum Likelihood, Aikaikes's Information Criteria and Schwarz's Bayesian Information Criteria were the criteria for choice of the best fit.For growth traits, contemporary groups (CG) were formed by grouping animals born in the same year-season and with the same sex, genetic group and birth type . Only CGs with a minimum of five animals were considered. The birth seasons were: season 1 - January, February and March, season 2 - April, May and June, season 3 - July, August and September, and season 4 - October, November and December.For reproductive and maternal traits, two CGs were created: the first for AFL and the second for other traits. For AFL, the CG consisted of animals born in the same year-season, of the same genetic group, birth type  and interaction of birth type with lamb sex . For the other traits, the CGs consisted of animals of the same genetic group, with lambing in the same year-season, the same birth type  and the same lambing order. Only CGs with a minimum of five animals were considered.After preliminary analysis and based on criteria used to determine the best fit, the following fixed models were used, depending on the trait:BW - contemporary group and age class of the dam at lambing (1 to 8 years);WW and GBW - contemporary group, age class of the dam at lambing and lamb age (days) at weaning as linear and quadratic covariates;SW and GWS - contemporary group and animal age (days) at slaughter as the covariate (linear and quadratic);YW and GWY - contemporary group and animal age (days) on the date the animal was weighed as the covariate (linear and quadratic);AFL, LI, GL, LD, TBW and TWW - contemporary groups.-4, 2) a change in parameters of < 10-8 and 3) a gradient vector norm < 10-3.The (co)variances and genetic parameters were estimated by the Average Information Restricted Maximum Likelihood method (AI-REML) using the software WOMBAT , with siThe relationship matrix included 16,808 animals. Of these, 75 were rams and 4,272 were ewes, 13,124 animals had a complete pedigree (sire and dam known) and 1,251 were from the basal flock; 224 animals had an unknown sire. There was an average of 156 lambs per ram and 901 lambs per ram breed.The general model for growth traits was:Y is a (N x 1) vector of observations, β is the vector of fixed effects related to the incidence matrix X, a is the vector of direct genetic effects related to the incidence matrix Z1, m is the vector of maternal genetic effects related to the incidence matrix Z2, pe is the vector of permanent environmental maternal effects related to the incidence matrix Z3, and e is the vector of random residuals.where Z2m and Z3pe were not included in the analysis of SW, YW, GWS and GWY. BW, WW and SW were analyzed in a multiple trait model. YW was analyzed in a multiple trait model with BW and WW. GBW was analyzed with GWS in one analysis and with GWY in another analysis.The fixed effects have already been described previously. The general model presented above was used for BW, WW and GBW. The components Z2m component was not considered and the Z3pe component refers to permanent environmental effects on the animal and was included only for traits measured many times on the same animal . These two components were not included for AFL. AFL, LI and GL were analyzed in a multiple trait model, as were TBW and TWW. LD was analyzed in a single trait model.Using the same general model described previously for all reproductive and maternal traits, the i.e., there was no specific design in the breeding pattern used. As an initial simplification in the data analysis, the average effect (additive and non-additive) of the genetic groups was considered to be fixed.The crossbreeding in this population was completely random, The number of observations and the means for the traits analyzed are shown in The estimates of (co)variance, Log L value, heritabilities and genetic correlations for a multiple trait analysis for BW, WW and SW are summarized in vs. 0.35) but was lower for WW (0.60 vs. 0.81). The genetic correlations were high, with a maximum of 0.89 between BW and WW, as also observed in the analysis with BW, WW and SW. Comparison of Tables The (co)variances, Log L value, heritabilities and genetic correlations for multiple trait analysis with GBW and GWS are summarized in The (co)variances, Log L value, heritabilities and genetic correlation for the maternal traits LWB and LWW are shown in e.g., 0.12 and 0.21 for Poll Dorset sheep  of -0.47 and -0.24 between the direct and maternal effects for BW and WW, respectively, in purebred Santa Inês. These values were similar to those observed here, possibly because this breed provided the largest contribution to the flock in our study. am of -0.56 and -0.35 for BW in Hampshire Down and Poll Dorset sheep, respectively. am of 0.03 for Belgian Texel sheep and The (co)variance and correlation estimates between animal and maternal genetic effects were generally negative for all traits. There is a lack of information on the genetic parameters for YW in Brazilian flocks. The high correlations between BW and WW (0.83), BW and SW (0.70) and WW and SW (0.92) indicated the possibility of a correlated response with the selection for a given trait. The greater heritability of SW and the high correlation between WW and SW suggested that animals may be selected at an early age.Genetic correlations ranging from -0.33 to 0.81 have been reported between BW and WW in different breeds and at different ages  and maternal (0.06) heritabilities for GBW  were simvs. environmental interactions. In the pre-weaning period, the animals were maintained in confined conditions, whereas after weaning they had access to pasture and food supplementation.The negative correlations between GBW and GWS/GWY may reflect the limited number of observations for these parameters, partly because of the way the data were distributed. The animals in this flock were slaughtered between 120 and 150 days of age (128 on average), with only the males and females selected for reproduction reaching one year of age. Consequently, birth-to-weaning data were distributed into the weaning-to-slaughter and weaning-to-yearling groups. In addition, some lambs did not reach weaning. These negative correlations may also reflect differences in the animals responses to pre- and post-weaning environmental conditions, such as occurs in genotype AFL and LI were strongly influenced by environmental effects, whereas GL showed little inter-individual variation. Hence, the low heritabilities estimated for these traits were expected. A heritability of 0.27 for LI was estimated by According i.e., the ewes would be unable to express their full reproductive potential because the mating season was limited to a particular period. However, since in this flock the mating season was essentially continuous the year round, all of the ewes had an opportunity to mate at eight-month intervals.The similarity between the values for LD and LI suggests that these traits had essentially the same characteristics, possibly because of the reproductive management of the flock. The exposure of ewes to mating seasons meant that LI was probably not a good trait for selection because of possible bias. In this case, LD would probably be more efficient for selecting fertility because there would be no breeder-introduced bias, In conclusion, the results of this study show that there is strong maternal influence in this herd and the presence of sufficient genetic variation to allow mass selection for growth traits. Additive effects were of little importance for reproductive traits, and other strategies are necessary to improve the performance of these animals. However, the estimates presented here should be interpreted cautiously because of possible bias introduced by the absence of non-additive effects in the model used here. This model was chosen primarily because the lack of information on genetic parameters in Brazilian sheep precluded the choice of a more adequate one. Consequently, it is possible that the additive variance and heritability for some traits were overestimated. Nevertheless, the results described here provide a starting point for more detailed studies on the genetic parameters of multibreed sheep in Brazil.


Objective. To investigate the incidence of various antiphospholipid antibodies (aPLs), measured by commercial-based laboratory, with recurrent spontaneous abortion (RSA) patients and the impact of the species, isotype, titer, and number of positive aPLs on reproductive outcome in Japanese. Method. In this retrospective cohort study, 263 patients with RSA without possible causes were investigated. Of 131 patients with one or more positive aPL, 82 pregnant women under anticoagulant therapy were evaluated. Results. The incidence of various aPLs was almost consistent with previous report. Overall, successful pregnancy rate with anticoagulant therapy was 91.4% regardless of aPL profiles. There was no significant difference in the pregnancy maintenance rate between IgG and IgM groups or single positive and multiple positive groups, but there was a tendency for the rate with aspirin to be lower than with aspirin plus heparin in IgG group. Conclusion. aPL profile did not affect the pregnancy maintenance rate when anticoagulant therapy was actively introduced, however in IgG group, we recommend combination therapy with aspirin and heparin. For these patients met with above laboratory criteria and clinical criteria for APS, a treatment combining oral aspirin with the subcutaneous injection of unfractionated heparin has been regarded as superior to aspirin alone [ Since the pathogenic association of antiphospholipid antibody (aPL) with recurrent spontaneous abortions (RSA) was reported, the efficacy of anticoagulant therapy for patients that have undergone RSA and have positive aPL has been investigated –4. Regarin alone , 7. Howein alone , antiphoin alone , and othin alone  have beein alone . In Japaβ2GPI, and aCL described in the classification criteria for definite APS and investigated the impact of antibody titers by classifying them into weakly (from the 95th to the 99th percentile) and strongly (over the 99th percentile), antibody isotypes of IgG and IgM, and the numbers of positive antibodies of single and multiple on reproductive outcome. We designed this retrospective cohort study, and our study focused on the incidence of various aPLs with RSA patients, measured by commercial-based laboratory and the impact of their profiles on reproductive outcomes with active anticoagulant therapy in order to develop individualization of treatment for patients with RSA, because the subcutaneous injection of heparin requires daily self-injection during the entire period of pregnancy, so this treatment is very stressful for patients. Given the above background, we examined aPE and aPS of IgG and IgM antibodies in addition to LA, a This retrospective cohort study was designed to evaluate the incidence of various aPLs, measured by commercial-based laboratory, in patients that had undergone RSA and to determine whether aPL profiles affect reproductive outcomes with the anticoagulant therapy in order to develop individualization of treatment in these patients. The Jikei University Institutional Review Board approved the study design. Records were evaluated for 327 patients that had undergone RSA who visited the outpatient infertility clinic in Jikei University Hospital between November 2005 and July 2009. These patients had suffered 2 or more consecutive spontaneous abortions before the 12th week of gestation (= RSA patients) and were examined by routine checkup for RSA. Then, 64 patients were positive for routine checkup that included anatomical, endocrine, or chromosomal aberration, complications of SLE, or other autoimmune diseases. Of 263 patients negative for routine checkup, various aPLs were measured by commercial-based laboratory, defined 95th percentile and more as positive. Then 132 patients were negative for any aPLs and 131 patients revealed positive for one or more aPL. These 131 patients were treated with the anticoagulant therapy, following which, 82 patients conceived. Of the 82 cases of conception, 74 maintained pregnancy successfully, and 8 cases had a miscarriage before the 12th week of pregnancy. Among these miscarriages, 7 cases exhibited normal karyotypes of aborted villi and 1 case had chromosomal aberration. Therefore, with the exception of the case involving chromosomal aberration, a total of 81 cases were analyzed for reproductive outcomes with the anticoagulant therapy. Pregnancy maintenance was defined as the pregnancy continuing beyond the 24th week and resulting in the delivery of a live-born neonate.β2GPI, aCL-IgG and -IgM, aPE-IgG and -IgM, and aPS-IgG and -IgM. A commercial-based laboratory test company, SRL Laboratory , measured all these aPLs. Peripheral blood was drawn from the patients with negative routine checkup for RSA and various aPLs in serum and plasma were measured. At that time, patients were not pregnant. The test items concerning aPLs included LA, aβ2GPI was measured by ELISA [ LA was measured by the dilute Russell's viper venom time method  using a by ELISA , 15 usinby ELISA , and valby ELISA , 17 and  We performed anticoagulant therapy for all patients with one or more aPLs positive RSA women. The anticoagulant therapy consisted of two regimens, aspirin alone or aspirin plus heparin. A daily dose of 100 mg of aspirin was taken orally from prior to conception until the 32nd week of pregnancy, and subcutaneous self-injection of 5,000 units of unfractionated heparin calcium was administered twice a day, starting from the time when the presence of the gestational sac was confirmed in the uterus until the 37th week of pregnancy.Written informed consent concerning the application of anticoagulant therapies was obtained and the choice between these two regimens was left to patients.χ2 or Fisher exact test. Differences between the two groups were analyzed for significance with the β2GPI (1/263: 0.4%). As for the incidence of aPLs by isotype, in both aCL and aPS, IgM-isotype was more frequent than IgG-isotype and in aPE, IgM-isotype and IgG-isotype have the same frequency. As for the incidence of aPLs by the titer, in the weakly positive group (from the 95th to the 99th percentile), the positive rates of aPL ranged from 0.4% (1/263: aβ2GPI) to 19.4% (51/263: aPS-IgM), and in the strongly positive group (over the 99th percentile), those of aPL ranged from 0% (0/263: aβ2GPI) to 8.4% (22/263: aPS-IgM). Comparing the incidence between these two groups, a higher incidence was found in the weakly positive group in all species of aPLs naturally. The incidence of various aPL profiles in two hundreds and sixty-three RSA patients without anatomical, endocrine, or chromosomal aberration, complication of SLE or other autoimmune diseases, was shown in P value of the difference between aCL-IgG (the highest rate of pregnancy maintenance: 100%) and aPS-IgM (the lowest rate of pregnancy maintenance: 88.1%) was 0.176, and that of aCL-IgG versus aPS-IgG was 0.277. As for the impact of the titer of aPLs, comparing the rate of pregnancy maintenance in the weakly positive group with that in the strongly positive group for each aPL, no significant difference was found among the six aPLs , and LA or aβ2GPI strongly positive case was not here. For instance, the lowest P value between weakly and strongly positive groups was 0.312 for aPE-IgG. As for the isotype (IgG or IgM group) and the number (single positive or multiple positive group) of positive aPLs, the impact of these on reproductive outcomes was investigated. . As for the number of positive aPLs, the rate of pregnancy maintenance in the 34 cases with a single positive group, with only one positive aPL, was 91.2% (31/34) and that in 47 cases with multiple positive group, with two or more positive aPLs, was 91.5% (43/47), also showing no significant difference between these two groups . The impact of various aPL profiles on reproductive outcomes was shown in Tables tigated.  Eighty-oFinally, we intended to identify a therapeutic principle for RSA patients with aPL.P value: 0.077). In IgM, single positive and multiple positive group, there was no difference in pregnancy maintenance rate between these two regimens. β2GPI of IgG or IgM isotype, and LA. Sugi et al. reported a higher frequency of aPE in patients with recurrent pregnancy loss before the 10th week of gestation than in healthy women: the frequencies of aPE-IgG, aPE-IgM, and aPE-IgA were 20.1%, 12.2%, and 1.4% in the patients, respectively, which were significantly higher than those in healthy women. These findings suggested that aPE is strongly associated with early pregnancy loss [In the field of obstetrics, APS has been mainly investigated with regard to its relationship with pregnancy loss, and therapy for aPL-positive recurrent pregnancy loss has been studied. Although many points concerning the mechanism of aPL-induced pregnancy loss remain unclear, according to a systemic review of RCT by Empson et al. , the folncy loss  and thatncy loss  and indincy loss , 19, andncy loss . The clincy loss , suggestncy loss .β2GPI was very low, only 0.4%. Those of other aPLs were found to be between 6.5% (aPS-IgG) and 17.9% (LA). This high positive rate, regarded the 95th percentile and more as positive, for aCL-IgM and aPS-IgM in RSA women was five times as high as normal Japanese population, and aCL and aPS may have had stronger association with RSA than aβ2GPI, consistent with previous reports [β2GPI were more scarce than normal Japanese population , suggesting relatively high association with early RSA and IgG or IgM of aCL, aPE, and aPS. In this study, concerning individual aPL without regarding the titer, the positive rates of aCL-IgM and aPS-IgM exceeded 25%, while that of a reports , 22. Witβ2GPI for strongly positive conceived patient in this study, with regard to the titer of each aPL, upon comparing the pregnancy maintenance rate of weakly positive with strongly positive groups for each aPL, no significant differences were found for all 8 aPLs  in aPS-IgM-positive cases was the lowest, but there was no significant difference among the other eight aPLs in terms of the rate of pregnancy maintenance. There was no LA and al 8 aPLs . As mentβ2GPI had other aPLs measured in this study. The rate of pregnancy maintenance in the IgM group was 90.0% and that in the IgG group was 92.7%, showing no significant difference. With regard to the number of positive aPLs, the rate of pregnancy maintenance in 34 cases with single aPL was 91.2% and that in 47 cases with multiple aPLs was 91.5%, also showing no significant difference , showing a benefit of combination therapy for IgG group and higher pathogenicity in the IgG than IgM group. Moreover, the rate of pregnancy maintenance did not differ between patients treated with aspirin alone and those with a combination of aspirin plus heparin in the IgM group, so aspirin therapy alone is sufficient for the IgM group because heparin therapy was very stressful for patients. As mentioned before [Finally, we intended to identify a therapeutic principle for RSA patients with aPL. There was a tendency for the rate of pregnancy maintenance with aspirin alone to be lower than that with aspirin plus heparin in the IgG group; however, no significant difference was found , including patient overlap for aPL positivities and not RCT but retrospective cohort study. This pregnancy maintenance rate is as high as normal Japanese population after an intrauterine pregnancy has been seen by ultrasound, and this study may include normal population because we have resulted from the 95th to the 99th percentile as weakly positive. The interpretation of the result needs to be careful and the accumulation of additional cases and more detailed investigations may be necessary.β2GPI in RSA patients, we have to test these aPLs for RSA patients checkup. The patients suffering from RSA with some aPLs and do not meet criteria for APS resulted in normal pregnancy outcome by active anticoagulant therapy regardless of the positive antibody species, titer, and the number. In terms of the pathogenicity of aPLs, IgG isotype may be stronger than IgM isotype, so we recommend combination therapy with aspirin and heparin for IgG-positive RSA patients.Because IgG or IgM of aCL, aPE, and aPS were more frequent than LAC or a


Objective. Children with epilepsy are at risk for less than optimum long-term outcomes. The type and severity of their epilepsy may contribute to educational, psychological, and social outcomes. The objective of this study was to determine the relation between somatization and adaptive skills based on seizure type that could impact on those outcomes. Methods. This study examined adaptive functioning and somatization in 87 children with epilepsy using archival data from a tertiary care facility. Results. No significant differences in adaptive skills emerged between groups of children diagnosed with complex partial (CP) as compared to CP-secondary generalized (SG) seizures; however, deficits in adaptive behavior were found for both groups. The number of medications, possibly reflecting the severity of the epilepsy, was highly correlated to adaptive function. Conclusions. Identification of deficits in adaptive behavior may represent an opportunity for tailored prevention and intervention programming for children with epilepsy. Addressing functional deficits may lead to improved outcomes for these children. Among chronic illnesses, epilepsy is the most common neurological condition in childhood –3. ChildStudies have highlighted the relationship between seizure variables , psychological well-being, and independent functioning , 12–16. At best, Sillanpää and Cross  found thIn addition to potentially impaired adaptive skills, associated with health and medical concerns, children with epilepsy may exhibit a higher than expected level of somatic complaints, potentially indicative of somatization. From a psychological perspective, somatization is best described as the presentation of a psychological problem  as a physical complaint. Specific behaviors  in an otherwise healthy individual oftentimes are interpreted in this manner. For children with epilepsy, these behaviors may reflect the medical condition as opposed to (or in addition to) an underlying psychological problem. Somatic complaints have been found to be more common among children with lower cognitive abilities ; thus, tAlthough epilepsy is by far one of the most studied and explored chronic illnesses, research has not examined the relationship between somatization and general adaptive functioning to the same extent that risk for psychopathology has been explored. Existing data suggest that the presence of epilepsy increases the likelihood of somatic complaints and low adaptive skills. The likelihood of these problems developing is increased by poor cognitive functioning and behavioral problems, potentially contributing to social skill deficits , 27, 28.This is a retrospective study using extant data of children and adolescents with epilepsy who were referred to a tertiary care epilepsy center in the south for neuropsychology evaluation between the years of 1997 and 2010. The 87 participants included those individuals with epilepsy who meet the criteria for inclusion. Children were included if (a) they were between the ages of 4 and 17, (b) they had been administered a version of the Behavior Assessment System for Children BASC /BASC-2  Parent RN = 87) were predominantly male (59.77%) and Caucasian (72.41%). The participants had a mean age of 10.65 (SD = 2.89). The participants' cognitive ability ranged from 70 to 115, with a mean IQ of 86.26 (SD = 10.89). Of the participants, 64 (73.56%) had a diagnosis of CP and 23 (26.44%) had a diagnosis of SG. The two groups did not differ in age at the time of assessment or full scale IQ. Seizure variables of interest included age of onset, duration, and number of medications. In particular, number of medications was used as an indicator of severity; number of medications for both groups ranged from 0 to 3. Most frequent antiepileptic medications included one or more of the following: oxcarbazepine (36% of participants), levetiracetam (28%), carbamazepine (22%), lamotrigine (19%), or valproate (16%). No between group differences were found for age at onset, duration, or number of medications. Similarly, chi-square analyses indicated that groups did not differ significantly in sex, race/ethnicity, or reported family income. Participants  and then by the Texas A&M University IRB to use the extant data base. Because the data for this study were archival, collection and coding systems were already established. Demographic information including age, race/ethnicity, gender, income, and type of epilepsy, as well as dependent and independent variables used in this study, was provided in the database. Only those cases meeting the inclusion and exclusion criteria were retained. Data were collected from comprehensive neuropsychological reports completed with appropriate parental and child consent at the tertiary care epilepsy center. The dependent variables that were examined in this study were the adaptive skills and level of somatization as reported by parents and teachers, as well as specific epilepsy-related variables.Wechsler Intelligence Scale for Children [r = 0.89). For this sample, 51 (68.62%) of the participants were administered the WISC-IV.Children , 33. TheBehavior Assessment System for Children , 31. The BASC/BASC-2 is used to evaluate the behavior and self-perceptions of children and adults aged 2 through 25 years of age. The BASC/BASC-2 includes forms for preschool, child, and adolescent. The BASC/BASC-2 has been well recognized as an appropriate instrument for the evaluation of behavior in children and adolescents [lescents . There alescents , 35.For the purposes of this study, the variables of interest included the adaptive skills subscale scores, as well as the somatization subscale from the internalizing composite. The adaptive skills composite includes the following subscales: adaptability, social skills, functional communication, leadership, learning problems (teacher only), study skills (teacher only), and activities of daily living (parent only) depending on the form and version used. The coefficient alpha across forms and version is greater than .80 except for the activities of daily living subscale (.72–.76).The Somatization subscale assesses the tendency of the child or adolescent to be report physical complaints or seek medical intervention. It is composed of items that cover topics including doctors' visits and physical ailments . The reliability coefficients for the somatization subscale for children aged 6 to 18 range from .79 to .84. Convergent validity for this subscale has been demonstrated as well , 31.For this study, both child and adolescent forms were administered depending upon the child's age. It should be noted that not all forms included all subscales. Further, using retrospective data meant that some participants had the original BASC and others had the BASC-2. Although correlations between the composite scores for the two versions are good (.89–.98), the functional communication subscale was not a component of the BASC. As a result of the differences in forms, the number of participants who had specific scales varies based on age, form (parent/teacher), and version.Preliminary analyses were performed to ensure no violation of the assumptions of normality, linearity, and homoscedasticity on the dependent variables. Across BASC/BASC-2 variables and epilepsy variables , no variables violated assumptions. To compare by seizure type, a two-group design was used. It was hypothesized that the two groups, CP and SG, would differ in level of somatic complaints as well as adaptive skills. Correlational analyses were used to examine relations between variables. Alpha was set at .05 so as to reduce the likelihood of type II error, the greater concern in a small clinical sample. All analyses were conducted using SPSS.P < .05, partial eta-squared = .08) and study skills . Specifically, as predicted, the SG group mean scores on these subscales were lower than those of the CP group.It was hypothesized that the children and adolescents in the SG group would demonstrate more difficulties in adaptive functioning and higher somatization scores than those in the CP group. One-way analysis of variance was used to evaluate the differences between epilepsy groups for the BASC/BASC-2 teacher and parent reports. While no significant between group differences were found for parent reports, the groups differed on the teacher ratings of leadership  was used to determine the relation between age of onset, duration, and number of medications with each of the adaptive skills subscales for the entire sample, as well as for somatization (see P > .05), Leadership, (P < .05), and activities of daily living (P < .01), with more somatic complaints and lower adaptive skills associated with more medications needed for seizure control . For teacher ratings, no significant associations were found with epilepsy variables.It was hypothesized, for both the parent and teacher reports, that the younger the age at onset of seizures is, the longer the duration of living with the illness and number of medications taken would be correlated with adaptive skills deficits. Correlation . The differences between parent and teacher ratings are common [P = .02) and leadership (P = .01). Teacher-rated somatization was also significantly correlated with teacher-rated Social Skills (P < .05), leadership (P = .04), Study Skills (P = .007), and functional communication (P = .02). In all cases, a higher level of somatic complaints was associated with lower adaptive skills as expected.It was hypothesized that somatization scores would be inversely related to adaptive functioning for both the parent and teacher report, both presumed to reflect severity and impact on functioning. Correlation analysis was conducted to ascertain whether a relationship existed between level of somatic complaints and the adaptive skills subscales as measured by the BASC/BASC-2 parent and teacher reports. The results see  indicatee common . These dThe long term outcome for children with epilepsy tends to be less than optimum , 11, 25.Parents and teachers identified some differing aspects of adaptive behavior to be of concern; these differences likely reflect the differing contextual demands. Surprisingly, neither age of onset nor time since diagnosis was correlated with the somatization or any of the adaptive skills subscales. In contrast, number of medications was significantly correlated with parent-rated, but not teacher-rated adaptive behavior. For all three significant parent subscales, the ratings were lower as the number of medications  increased.When exploring the relation between somatization and adaptive skills, results did not indicate parent ratings of somatization to be related to adaptive skills. In contrast, for teacher ratings, there was an inverse relation such that higher levels of somatic complaints were associated with specific adaptive behaviors . Because the somatization subscale emphasizes physical aches and pains, medications, and medical treatments, these findings suggest that the higher the degree of symptomology the child is experiencing due to their illness, particularly in the school setting, the less likely they are to actively engage and participate in the classroom.Somatic complaints may be expected in children and adolescents with epilepsy and other chronic illnesses. As a result, somatization scales may sometimes be elevated for children with epilepsy because of factors related to the seizure disorder rather than because of psychopathology. At the same time, experiencing somatic issues related to epilepsy can have an effect on other areas of development, particularly adaptive skills. Identification of adaptive skills deficits may represent an opportunity for tailored prevention and intervention programming for children with epilepsy to improve their overall outcome. For example, if social competence is the area of concern, implementation of social emotional learning program may be appropriate; if peer relations is the area of concern, a social skills program might be considered. As such, more comprehensive assessment of adaptive skills may be appropriate for children with epilepsy regardless of cognitive ability in order to identify adaptive skills in need of support or intervention . Additio


Social inequalities in cardiovascular diseases are well documented. Yet, the relation of social status inconsistency  and medical conditions of heart or vessels is not clear. Status inconsistency (SI) is assumed to be stressful, and the association of psychosocial distress and health is well known. Therefore, we aimed to analyze the relationship between cardiovascular diseases (CVD) and status inconsistency. Another target was to assess the influence of behaviour related risk factors on this association.8960 men and 6070 women, aged 45-65 years, from the EPIC-Heidelberg cohort (European Prospective Investigation into Cancer and Nutrition) were included. Socio-economic status was assessed by education/vocational training and occupational position at recruitment. During a median follow-up of 8.7 years, information on CVD was collected.Compared to status consistent subjects, men who were in a higher occupational position than could be expected given their educational attainment had a nearly two-fold increased incidence of CVD (Odds Ratio (OR) = 1.8, 95% Confidence Interval (CI) = 1.5; 2.4, adjusted for age). Smoking behaviour and BMI differed significantly between those who had adequate occupational positions and those who did not. Yet, these lifestyle factors, as opposed to age, did not contribute to the observed differences in CVD. No association of cardiovascular diseases and status inconsistency was found for women or in cases where education exceeded occupational position.Status inconsistent men  had a higher risk of cardiovascular diseases than status consistent men. However, harmful behaviour did not explain this relationship. Cardiovascular diseases (CVD) are a major health problem in developed countries. According to the WHO, about 17 million people die of CVD every year, particularly of myocardial infarctions (MI) and strokes -5.Educational attainment, occupational position and income are established indicators of social status, indicating the (relative) rank an individual holds in society. Each of the above indicators has been shown to be inversely associated with CVD. Yet, it is not clear whether status inconsistency (SI), i.e. occupying discrepant positions in two or more of these ranking systems, affects health. One prominent example of such a mismatch is a university graduate working as a taxi driver. Status inconsistency is common in modern societies . A low cPsychosocial distress, on the other hand, is regarded as being causally related to CVD ,16. NoneTo our knowledge, only little research has been conducted to examine the linkage between status inconsistency, health related behaviour and medical conditions. Thus, the aim of our study was (1) to investigate the association between social status inconsistency and CVD  in the general population. Further (2), we wanted to explore which proportion of this association is explained by behavioural factors.Data were gathered from the European Prospective Investigation into Cancer and Nutrition (EPIC) Study in Heidelberg, one of the largest cohort studies on the influence of diet and lifestyle factors on chronic diseases. Details of recruitment and follow-up procedures were described elsewhere ,27. BrieApproximately every two years a follow-up questionnaire was mailed to the study participants, asking for diagnosed chronic conditions and the year of diagnosis. The participation rate in all follow-up rounds was more than 90% of all eligible study participants. The investigation was approved by the ethics committee at the University of Heidelberg.For the present paper, we limited our study sample to subjects 40 to 65 years of age who held at least a half time employment at recruitment. Thus, the analytical cohort comprised 15980 subjects with a median follow up period of 8.7 years.At recruitment, diagnoses of myocardial infarction (MI) and stroke were recorded by means of a self-administered questionnaire, asking whether a doctor ever had diagnosed MI or stroke. In the following years incident CVD events were identified by follow-up with questionnaire or mortality registers. Thereby, non-fatal events were ascertained by record linkage and reviews of medical records.After the exclusion of subjects with prevalent events at baseline , we identified the following number of events: 185 cases of stroke, 280 of MI, 12 cases with stroke and MI. We excluded further cases  where the status of events  was unknown. For reasons of small numbers, we collapsed the two outcome variables under the headline cardiovascular diseases.Occupational position, recorded in twenty categories, was collapsed into 5 groups: 1 = un-skilled, semi-skilled manual or non-manual workers, 2 = skilled manual workers or non-manual workers with simple task, 3 = non-manual workers with middle task, middle level civil service, 4 = intermediates and 5 = professionals. Since the occupational status of farmers and family workers is ambiguous, we excluded subjects with these professions from the analyses.Education was measured according to the German school system. We completed the information by using information on vocational training. Similarly to occupational status, we divided education/vocational training into 5 classes, namely, 1 = < 10 years of education without vocational training, 2 = < 10 years with vocational training, 3 = > = 10 years without vocational training, 4 = > = 10 years with vocational training, 5 = university .SI was calculated according to Peter, Gässler, Geyer (2007)  by subtr2 or higher for men, and 27.5 kg/m2 or higher for women respectively, which corresponded to the 75th percentile of those who were not affected by CVD. We also used the 75th percentile of the healthy population as cut-off point for dichotomising the alcohol consumption. Diabetes was self-reported and dichotomized into reported or not .Further covariates hypothesized to be potential confounders of the relationship between SI and CVD were introduced in multivariate analyses. Age was collapsed into two groups . Smoking status was self-reported and classified into 0 = never/former smoker and 1 = current smoker. Physical activity was classified as 1 = inactive or moderately inactive vs. 0 = moderately active and active, based on occupational activity, cycling, and sports . ElevateAnalyses were performed stratified by sex. Odds Ratios (OR) and 95% confidence intervals (95%-CI) are presented for the associations between SI and CVD. In order to quantify the impact of status inconsistency on health behaviour and BMI, we calculated ORs, considering behaviour related risk factors and BMI as outcome and status inconsistency as independent variable. SAS statistical software 9.13  was used for all calculations.Baseline data on 6070 Women and 8960 Men are displayed in Table Subjects analyzed were well educated and had elevated occupational positions.Marked gender differences were found in the distribution of status inconsistency. SI in terms of higher occupational position compared to education was more prevalent for men (15.1%) than for women (8.0%). On the other hand, a combination of high education and low occupation was predominant among women (9.0% vs. 5.7% in men). Younger subjects were more likely to be status inconsistent in terms of being higher qualified compared to their occupation (data not shown in the table). With regard to the other groups, men with low education occupying higher occupational positions showed the highest incidence of CVD  < 0.001)  on CVD was only limited  into the composite outcome variable. Results did not differ substantially from those presented here.In this study, low education in combination with high occupation was related to CVD in men, but not in women. Men with low educational status working in a higher occupational position had a nearly two-fold increased incidence of CVD than men without SI. Yet, we did not find any effect of high education combined with low occupation as hypothesized. Smoking behaviour, physical activity and BMI differed between status inconsistent individuals and the reference group. However, the effect of SI on cardiovascular health was not explained by health behaviour. The fit of respective models was limited.The EPIC-Heidelberg sample was well educated and held high occupational positions at baseline which is characteristic of the population in Heidelberg. Heidelberg, located in the south west of Germany, is Germany's oldest university town with the country's highest percentage of graduates (more than 50%), a higher-than-average income, and a comparatively young population ,30. ThisConcerning the outcome we found a restricted number of events, even though similar to the rate in Germany, given a mean follow-up period of nearly 9 years -33. ThisOur results show 15% of men and 8% of women to be status inconsistent, with low education but relatively high occupational position. These rates are approximately in line with Groot, Maassen van den Brink 2000  but loweWe assume that the restricted number of SI and a small incidence of CVD in women could be one reason why we did not find an association of CVD and SI in female subjects.The small number of events may also affect the associations between "traditionally examined" social indicators and CVD. Though the estimates of the risks showed a social gradient in the incidence of CVD, they did not reach statistical significance.occupational distress is currently studied by our group.Although psychosocial distress is not measured in this study, several other investigations showed that SI is associated with increased psychosocial distress because of relative deprivation or distributive injustice . Psychological distress elicited by the other type of SI  may be induced by work overload. However, to our knowledge the mediating effect of psychosocial factors in the association between SI and health has not been investigated so far. The mediating effect of Hart et al. 1998  found feWe found a higher risk for smoking and of being overweight in status inconsistent men. Although these results are not in line with the above mentioned studies, one could interpret these findings in the light of psychological distress. Episodes of higher stress levels are related to smoking , and weiConcerning the relationship between status inconsistency and cardiovascular diseases, older studies showed conflicting results , thus we hypothesize that similar results can hold true for all modernized countries. Authors from the Czech Republic  underlinEPIC-Heidelberg, one of the largest cohort studies of chronic diseases, is of particular interest because it provides longitudinal data from the general population. By excluding subjects with prevalent CVD before recruitment, reversed causality - career mobility caused by CVD morbidity - is excluded. Furthermore, to our knowledge, there is no other study analyzing the association of status inconsistency and health outcomes that are ascertained by reviews of medical records or mortality registers.Some potential limitations of our study should be considered: First, due to a small number of events, we had to collapse two outcome variables, stroke and MI. Second, since data on income was not available in EPIC-Heidelberg we did not analyze further forms of SI arising, e.g. income exceeding occupational position/educational attainment or vice versa.Our models only explained a small partition of the overall variability. Yet, the model fit is better compared to models using education/vocational training and occupational position as separate independent variables. Thus, we conclude that information on status inconsistency may help to further improve knowledge about social inequality in health.There is a broad discussion concerning the correct model specification to quantify the effects of status inconsistency. Simpson 1985  and ZhanStatus inconsistent men had a higher risk of CVD than occupationally stable individuals, whereas we only found inconsistent associations of single indicators of social status with cardiovascular diseases. Health related risk factors like smoking and BMI were associated with status inconsistency. However, harmful behaviour did not explain the relationship between status inconsistency and CVD.The authors declare that they have no competing interests.GN and RP initiated and designed the project. JL is principal investigator of the EPIC-Heidelberg cohort study and contributed to the study design. SR and SH were involved in data collection and contributed to the variable selection. All authors provided specialist knowledge in the advancement of the analyses and provided input in re-drafting the manuscript. SB conducted the statistical analyses and wrote the manuscript, which was seen and approved by all authors.The EPIC-Heidelberg study was funded by "Europe Against Cancer" Program of the Euro-pean Commission (SANCO); German Cancer Aid; German Cancer Research Center; German Federal Ministry of Education and Research, and Kurt-Eberhard-Bode-Stiftung.The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1471-2458/11/104/prepub


Introduction. Although alcohol abuse is associated with hypertension in whites and nonwhites, it has been scarcely investigated in HIV-infected patients. Objective. To investigate whether the association of alcohol abuse with hypertension is influenced by skin color in HIV-infected individuals. Methods. Cross-sectional study in HIV-infected individuals aged 18 years or older. Demographic characteristics, lifestyle, and HIV infection were investigated. Alcohol abuse was defined as ≥15 (women) and ≥30 g/alcohol/day (men), and binge drinking by the intake of ≥5 drinks on a single occasion. Hypertension was defined by blood pressure ≥140/90 mmHg or use of blood pressure-lowering agents. Results. We studied 1,240 individuals, with 39.1 ± 10 years, 51% males and 57% whites. Age and body mass index were associated with blood pressure, and there was an independent association of alcohol abuse with hypertension in whites  and nonwhites . Among nonwhite individuals who were alcohol abusers, systolic  and diastolic blood pressures  were higher than in nonabusers. Conclusion. Alcohol abuse is a risk factor for hypertension in white and nonwhite HIV-infected individuals. The association of ethanol consumption with blood pressure is not explained by AIDS-related conditions. Hypertension is a major cardiovascular risk factor worldwide. Projections are that, by the year of 2025, 75.0% (or 1.17 billion people) of the people with hypertension in the world will be living in emerging nations , regardlRisk factors for cardiovascular diseases, including hypertension and dyslipidemia, are determinants of reduced life expectancy in HIV-infected patients . HyperteThe relationship between alcohol consumption and hypertension may be influenced by some characteristics, such as skin color , 22. SkiWe conducted a cross-sectional study including HIV-infected individuals who were being followed up at the Outpatient Clinic of the Care and Therapy Service (SAT), Hospital Sanatório Partenon, State Department of Health of Rio Grande do Sul, Brazil. This clinic and all public health care centers provide medical care, antiretroviral therapy (ART), antihypertensives, and other medications free of charge for HIV-infected patients. We consecutively enrolled female and male patients, aged 18 or older, who were seen between June 2006 and December 2008. Pregnant women, individuals who were unable to provide written consent, or those incarcerated were excluded. Participants who were under the influence of alcohol or drugs at the time of the interview were asked to return for evaluation at another time. 3/mL), viral load (copies per mL of blood), and clinical information were confirmed by medical records. Alcohol consumption was investigated using a validated quantity-frequency questionnaire based on the kind of beverage consumed [Participants were interviewed on the day of the regular medical appointments. Since they had to consult every month, in order to get antiretroviral medication, they were seen often, which contributed to achieving high participation rate. Information was collected, using standardized questionnaires, for the following characteristics: demographic , socioeconomic , and lifestyle characteristics , as well as the use of antiretroviral therapy (ART), and time since diagnosis of HIV infection . Data related to HIV infection as CD4 lymphocyte count  was calculated as the weight (kg) divided by the square of the height (m) and classified as normal (<25.0), overweight (25–29.9), and obesity (≥30.0). Standardized measurements of blood pressure were obtained in duplicate in two visits, using a validated oscillometric device (OMRON CP-705) [Weight (Kg) and height (m) were measured twice with the participants being barefoot and wearing light clothes, using an anthropometric scale . Body mass index  . The ave normal <.0, overwCertified researchers performed the interviews and measured anthropometric parameters and blood pressure. Approximately 5% of the interviews were repeated for quality control. Data were entered twice into the database of Epinfo, version 2000. The study was approved by the Research Ethics Committee of the Hospital de Clínicas de Porto Alegre, which is accredited by the Office of Human Research Protections. All participants signed an informed consent form. Sample Size Calculation and Statistical Analysis. Sample size calculation was based on the estimated prevalence of hypertension between white and nonwhite participants with abusive alcohol consumption  and abstemious drinking (18%), with 80% of power and a significance level of 0.05 (two-tailed). A sample size of 738 white and 398 nonwhite participants with a 1 : 5 ratio for exposed and unexposed participants to excessive alcohol consumption would be required to detect a hazard ratio of at least 1.7. The estimates were based on previous studies [ studies , 29.P values lower than or equal to 0.2 in unadjusted analysis. Age, sex, educational attainment, smoking, physical activity, body mass index, time since HIV infection, and lifetime HAART use were considered confounding factors used in the multivariate models for whites and nonwhites. Partially adjusted models of alcohol consumption with systolic or diastolic blood pressure, including age, sex, and educational attainment, were run in order to better understand the associations and to interpret the risk ratios. A trend for association was determined by P values between 0.05 and 0.1.Characteristics of the sample were expressed as mean and standard deviation. We used Pearson's chi-square test for the analysis of categorical variables and analysis of variance (continuous variables) to assess the association between these factors and the different outcomes. Confounding factors were controlled using the modified Poisson regression (robust variance estimates)  and analOf the 1,295 HIV-infected patients screened, 1,255 were eligible and 1,240 were included. Thus, forty patients had not confirmed eligibility due to age under 18 years, incarceration, or pregnancy; fifteen refused to participate, and two patients were included in a second attempt due to alcohol intoxication at the first visit. Characteristics of the overall sample are presented in Risk factors for hypertension among whites and nonwhites are shown in Systolic and diastolic blood pressure was higher exclusively in nonwhite participants who abused alcohol, independently of confounding factors . SystoliIn this study, we found that the consumption of large amounts of alcohol was independently associated with hypertension in white and nonwhite HIV-infected individuals. Blood pressure, on the other hand, was higher exclusively in nonwhite abusers of ethanol, demonstrated after adjustment for confounding factors. However, even partially adjusted models showed the presence of negative confounding factors. Among, whites there was an association of blood pressure with the frequency of consumption. Taken together, these findings suggest that among nonwhite participants quantity is more important than the pattern of consumption, while for whites the frequency of drinking is more relevant.The association between alcohol abuse and hypertension identified in our study is in agreement with findings from other populations . The assOur study adds a piece of mind in the investigation of the influence of HIV-related characteristics and higher incidence of cardiovascular disease. It has been suggested that the use of HAART may be associated with increasing blood pressure , 35, 36.Some limitations of our study deserve to be mentioned. The cross-sectional design does not allow inferring causality. Data on alcohol consumption were obtained from a standardized questionnaire containing detailed information, but it relies on memory, and because it was applied in the context of medical care, this might have led individuals to underreport consumption. Another aspect to be considered is the fact that blood pressure measurements were performed at the medical consultation, and therefore the possibility of a white coat effect cannot be discarded. Even underreporting alcohol consumption or the white coat effect, the association of alcohol abuse with hypertension has been confirmed by ambulatory monitoring of blood pressure . The proIn conclusion, alcohol abuse is associated with increased risk of hypertension in white and nonwhite HIV-infected individuals. Blood pressure is higher only in nonwhite individuals who abuse alcoholic beverages and in whites who drink weekly. The association of ethanol consumption with blood pressure is not explained by AIDS-related conditions.