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关键词： Childhood trauma   HiTOP   mental illness   psychopathology   trauma  

摘要： Background Dimensional models of psychopathology are increasingly common and there is evidence for the existence of a general dimension of psychopathology ('p'). The existing literature presents two ways to model p: as a bifactor or as a higher-order dimension. Bifactor models typically fit sample data better than higher-order models, and are often selected as better fitting alternatives but there are reasons to be cautious of such an approach to model selection. In this study the bifactor and higher-order models of p were compared in relation to associations with established risk variables for mental illness. Methods A trauma exposed community sample from the United Kingdom (N = 1051) completed self-report measures of 49 symptoms of psychopathology. Results A higher-order model with four first-order dimensions (Fear, Distress, Externalising and Thought Disorder) and a higher-order p dimension provided satisfactory model fit, and a bifactor representation provided superior model fit. Bifactor p and higher-order p were highly correlated (r = 0.97) indicating that both parametrisations produce near equivalent general dimensions of psychopathology. Latent variable models including predictor variables showed that the risk variables explained more variance in higher-order p than bifactor p. The higher-order model produced more interpretable associations for the first-order/specific dimensions compared to the bifactor model. Conclusions The higher-order representation of p, as described in the Hierarchical Taxonomy of Psychopathology, appears to be a more appropriate way to conceptualise the general dimension of psychopathology than the bifactor approach. The research and clinical implications of these discrepant ways of modelling p are discussed.

关键词： Antiinflammatory   antioxidant   apoptosis   lamotrigine   methylprednisolone   neuroprotection   rat   spinal cord   ischemia-reperfusion injury  

摘要： Introduction: Lamotrigine, an anticonvulsant drug with inhibition properties of multi-ion channels, has been shown to be able to attenuates secondary neuronal damage by influencing different pathways. The aim of this study was to look into whether lamotrigine treatment could protect the spinal cord from experimental spinal cord ischemia-reperfusion injury. Materials and methods: Thirty-two rats, eight rats per group, were randomly assigned to the sham group in which only laparotomy was performed, and to the ischemia, methylprednisolone and lamot-rigine groups, where the infrarenal aorta was clamped for thirty minutes to induce spinal cord ischemia-reperfusion injury. Tissue samples belonging to spinal cords were harvested from sacrificed animals twenty-four hours after reperfusion. Tumor necrosis factor-alpha levels, interleukin-1 beta levels, nitric oxide levels, superoxide dismutase activity, catalase activity, glutathione peroxidase activity, malondialde-hyde levels and caspase-3 activity were studied. Light and electron microscopic evaluations were also performed to reveal the pathological alterations. Basso, Beattie, and Bresnahan locomotor scale and the inclined-plane test was used to evaluate neurofunctional status at the beginning of the study and just before the animals were sacrificed. Results: Lamotrigine treatment provided significant improvement in the neurofunctional status by pre -venting the increase in cytokine expression, increased lipid peroxidation and oxidative stress, depletion of antioxidant enzymes activity and increased apoptosis, all of which contributing to spinal cord damage through different paths after ischemia reperfusion injury. Furthermore, lamotrigine treatment has shown improved results concerning the histopathological and ultrastructural scores and the functional tests. Conclusion: These results proposed that lamotrigine may be a useful therapeutic agent to prevent the neuronal damage developing after spinal cord ischemia-reperfus

关键词： Non-Hodgkin’   s lymphoma   Esophagus   Esophageal tumor  

摘要： Background The most frequent site for the extranodal appearance of primary non-Hodgkin's lymphomas (NHL) is the gastrointestinal (G.I.) tract. However, primary esophageal lymphoma is extremely rare. The purpose of the present study was to describe and analyze the demographics, clinical characteristics, histopathologic types, and long-term survival of patients with primary esophageal NHL registered in the surveillance, epidemiology, and end results (SEER) database. Methods Retrospective cohort study. Individuals with primary esophageal lymphoma (PEL) were identified using the international classification of disease for oncology, third edition histology codes. Patients were excluded if there was no microscopic confirmation of the neoplasm or if the diagnosis was made by autopsy or death certificate. Data on demographics, clinical characteristics, histopathology and survival were analyzed using the Kaplan-Meier method, life table, and cox proportional hazard models. Results 179 patients were included (68% males, median age 66 years [IQR 46-79]). The overall survival at 1, 5 and 10 years was 65% (95% CI 57.9-72.3%), 49% (95% CI 42.1-57.3%), and 31% (95% CI 24.5-38.6%), respectively. On univariate analyses, individuals with extranodal marginal zone lymphoma (MZL) had a significantly higher overall survival when compared to patients with diffuse large B cell lymphoma (HR 0.29;95% CI 0.11-0.73. p = 0.008). Furthermore, patients whose cancer was diagnosed after 1997 showed an improved overall survival (HR 0.40;95% CI 0.26-0.61. p < 0.001) when compared to those diagnosed before 1997. Conclusions In this large population-based series, diagnosis after 1997 (year of rituximab approval by the FDA) and MZL subtype were associated with improved survival outcomes in patients with PEL.

关键词： Leydig cell tumour   Pathology  

摘要： Testicular Leydig cell tumor (LCT), the most common sex-cord stromal tumor in men, represents a small fraction of all testicular tumors (similar to 1 to 3%). Although most testicular LCTs are indolent and cured by radical orchiectomy, 5-10% have aggressive biology and metastatic potential. In primary LCTs, large size, cytologic atypia, necrosis, increased mitotic activity, and vascular invasion have been associated with clinically aggressive tumors. From a molecular perspective, the characteristics of aggressive LCTs and the differences between aggressive and nonaggressive LCTs remain largely unexplored. This study compares the genomic landscape of aggressive and nonaggressive testicular LCTs. Twenty-six cases were analyzed using next-generation DNA sequencing (NGS) and immunohistochemistry. Cases were classified as aggressive LCT if they met published criteria for malignancy in primary (i.e., testicular) tumors or if they had pathology-proven metastatic disease;otherwise, cases were considered nonaggressive. This multi-institutional series included 18 aggressive LCTs (14 primary/testicular, 4 metastatic) and 8 nonaggressive LCTs. Two cases (2/26, 8%;both aggressive LCTs) failed sequencing and had negative (i.e., uninformative) FH immunohistochemistry results. One additional primary aggressive LCT failed sequencing but had informative FH immunohistochemistry results. Combined NGS and immunohistochemical analysis demonstrated FH inactivation in 5/26 cases (19%). In addition, NGS demonstrated CTNNB1 mutations or biallelic APC inactivation in 9/23 cases (39%), copy number changes without recurrent mutations in 6/23 (26%) cases, and no alterations in 4/23 cases (17%). CTNNB1 mutations were present in both aggressive and nonaggressive LCTs. In contrast, FH inactivation and multiple copy number changes were only identified in aggressive LCTs. In conclusion, three distinct subgroups of aggressive LCTs were characterized by FH inactivation, Wnt pathway activation, and copy

关键词： Logistic models   Magnetic resonance imaging   Osteosarcoma   Neoadjuvant therapy  

摘要： Objective To develop and validate a radiomics signature based on magnetic resonance imaging (MRI) from multicenter datasets for preoperative prediction of pathologic response to neoadjuvant chemotherapy (NAC) in patients with osteosarcoma. Methods We retrospectively enrolled 102 patients with histologically confirmed osteosarcoma who received chemotherapy before treatment from 4 hospitals (68 in the primary cohort and 34 in the external validation cohort). Quantitative imaging features were extracted from contrast-enhanced fat-suppressed T1-weighted images (CE FS T1WI). Four classification methods, i.e., the least absolute shrinkage and selection operator logistic regression (LASSO-LR), support vector machine (SVM), Gaussian process (GP), and Naive Bayes (NB) algorithm, were compared for feature selection and radiomics signature construction. The predictive performance of the radiomics signatures was assessed with the area under receiver operating characteristics curve (AUC), calibration curve, and decision curve analysis (DCA). Results Thirteen radiomics features selected based on the LASSO-LR classifier were adopted to construct the radiomics signature, which was significantly associated with the pathologic response. The prediction model achieved the best performance between good and poor responders with an AUC of 0.882 (95% CI, 0.837-0.918) in the primary cohort. Calibration curves showed good agreement. Similarly, findings were validated in the external validation cohort with good performance (AUC, 0.842 [95% CI, 0.793-0.883]) and good calibration. DCA analysis confirmed the clinical utility of the selected radiomics signature. Conclusion The constructed CE FS T1WI-radiomics signature with excellent performance could provide a potential tool to predict pathologic response to NAC in patients with osteosarcoma.

关键词： Gender   Fish   Heavy metal   Top predator   Bioaccumulation   Histological alterations  

摘要： Accumulation of 26 elements (Ag, Al, As, B, Ba, Ca, Cd, Co, Cr, Cu, Fe, Hg, K, Li, Mg, Mn, Mo, Na, Ni, P, Pb, S, Se, Si, Sr, and Zn) was analyzed in the gills, liver, and muscle of pikeperch males and females from Garasi reservoir using inductively coupled plasma optical emission spectrometry (ICP-OES). Histopathological (HP) changes in the gills and liver, and human health risk were also analyzed. The gills were most affected by metal pollution in both sexes. The concentrations of Hg in muscle tissue of four males, and Cd in two females and two males exceeded the maximum allowed concentrations. Statistical tests only revealed significant differences regarding the concentrations of Mg, K, and S in the muscle (higher in males) and Al, Ag, and Mn in the liver (higher in females) of individuals between sexes. Low to moderate levels of pathological changes were recorded for the gills and liver in both sexes. Significant differences between sexes were observed for inflammatory index of gills (I-GI) and HP index of gills (I-G), males had higher values compared to females, and for liver necrosis, where females had higher values compared to males. Gills were less affected by HP changes compared to the liver. There was no significant non-cancerogenic and cancerogenic health risk due to the consumption of pikeperch meat from the Garasi reservoir. However, women are under greater risk by consuming the meat of both male and female individuals, probably due to a longer lifetime and lesser body weight compared to the men.

关键词： Autism   Autism Spectrum Disorder (ASD)   Post-mortem studies   Systematic review  

摘要： Post-mortem studies allow for the direct investigation of brain tissue in those with autism and related disorders. Several review articles have focused on aspects of post-mortem abnormalities but none has brought together the entire post-mortem literature. Here, we systematically review the evidence from post-mortem studies of autism, and of related disorders that present with autistic features. The literature consists of a small body of studies with small sample sizes, but several remarkably consistent findings are evident. Cortical layering is largely undis-turbed, but there are consistent reductions in minicolumn numbers and aberrant myelination. Transcriptomics repeatedly implicate abberant synaptic, metabolic, proliferation, apoptosis and immune pathways. Sufficient replicated evidence is available to implicate non-coding RNA, aberrant epigenetic profiles, GABAergic, gluta-matergic and glial dysfunction in autism pathogenesis. Overall, the cerebellum and frontal cortex are most consistently implicated, sometimes revealing distinct region-specific alterations. The literature on related dis -orders such as Rett syndrome, Fragile X and copy number variations (CNVs) predisposing to autism is particu-larly small and inconclusive. Larger studies, matched for gender, developmental stage, co-morbidities and drug treatment are required.