bluuebunny/crossref_metadata_2025_split huggingface dataset:
Endoscopic resection with ligation using a multi-band mucosectomy system in Barrett’s esophagus with high-grade dysplasia and intramucosal carcinoma
Authors: Bhat Yasser M. , Furth Emma E. , Brensinger Colleen M. , Ginsberg Gregory G. 
Published: September 2009

Background: Endoscopic therapy for early neoplasia in Barrett’s esophagus (BE) is evolving. Endoscopic resection has an increasing role. We wanted to evaluate the safety and efficacy of multi-band ligation/resection [ER-L] without pre-injection in BE with high-grade dysplasia [HGD] and intramucosal carcinoma [IMCA]. Methods: A cohort of 65 consecutive patients from a single academic medical center, who underwent ER-L as part of endoscopic eradication therapy for BE with HGD/IMCA were studied. ER-L was performed after endoscopic mapping and endoscopic ultrasound (EUS). Subsequently, adjunctive ablative therapies including photodynamic therapy, argon plasma coagulation and radiofrequency ablation were applied to achieve complete eradication of all BE. Thereafter biopsy surveillance was performed per protocol. All patients were prescribed a proton-pump inhibitor. Main outcome measurements: Change in histopathological stage; eradication of BE and HGD/IMCA; adverse events. Results: The median number of ER-L applications in each session was 4 (range 1-6) and the mean total number of ER-L sessions was 1.5. Compared with prior forceps biopsy, histopathology from the ER-L specimen changed in 24 (37.5%, p =<0.0001). With median follow-up of 15 months (range 8-42), complete and durable BE eradication was achieved with ER-L alone in 36 (60%) and the remainder with adjunctive ablation therapies. There were nine complications (four (6%) acute bleeding, five (7.5%) strictures, zero perforations). Conclusions: ER-L without submucosal (SM) pre-injection is safe and effective when applied selectively for eradication of BE with HGD/IMCA. There is significant change in pathological stage after ER-L conferring a diagnostic and staging advantage. ER-L may be used adjunctively with ablation therapies.
Soluble lymphotoxin is an important effector molecule in GVHD and GVL
Authors: Markey Kate A. , Burman Angela C. , Banovic Tatjana , Kuns Rachel D. , Raffelt Neil C. , Rowe Vanessa , Olver Stuart D. , Don Alistair L. J. , Morris Edward S. , Pettit Allison R. , Wilson Yana A. , Robb Renee J. , Randall Louise M. , Korner Heinrich , Engwerda Christian R. , Clouston Andrew D. , MacDonald Kelli P. A. , Hill Geoffrey R. 
Published: September 2009

AbstractTumor necrosis factor (TNF) is a key cytokine in the effector phase of graft-versus-host disease (GVHD) after bone marrow transplantation, and TNF inhibitors have shown efficacy in clinical and experimental GVHD. TNF signals through the TNF receptors (TNFR), which also bind soluble lymphotoxin (LTα3), a TNF family member with a previously unexamined role in GVHD pathogenesis. We have used preclinical models to investigate the role of LT in GVHD. We confirm that grafts deficient in LTα have an attenuated capacity to induce GVHD equal to that seen when grafts lack TNF. This is not associated with other defects in cytokine production or T-cell function, suggesting that LTα3 exerts its pathogenic activity directly via TNFR signaling. We confirm that donor-derived LTα is required for graft-versus-leukemia (GVL) effects, with equal impairment in leukemic clearance seen in recipients of LTα- and TNF-deficient grafts. Further impairment in tumor clearance was seen using Tnf/Lta−/− donors, suggesting that these molecules play nonredundant roles in GVL. Importantly, donor TNF/LTα were only required for GVL where the recipient leukemia was susceptible to apoptosis via p55 TNFR signaling. These data suggest that antagonists neutralizing both TNF and LTα3 may be effective for treatment of GVHD, particularly if residual leukemia lacks the p55 TNFR.
The effects of BAFF and BAFF-R-Fc fusion protein in immune thrombocytopenia
Authors: Zhu Xiao-juan , Shi Yan , Peng Jun , Guo Cheng-shan , Shan Ning-ning , Qin Ping , Ji Xue-bin , Hou Ming 
Published: September 2009

Abstract
Elevated level of B-cell activating factor (BAFF) has been implicated in the pathogenesis of some autoimmune diseases. Blockade of receptor and ligand binding by decoy receptor has demonstrated a clinical benefit in both oncologic and immunologic diseases. In this report, we have detected plasma BAFF and BAFF mRNA expression in immune thrombocytopenia (ITP) patients by enzyme-linked immunosorbent assay (ELISA) and real-time quantitative reverse-transcription polymerase chain reaction (RT-PCR). The effects of recombinant human BAFF (rhBAFF) and BAFF-R-Fc fusion protein (BR3-Fc) on B cells, T cells, platelets, secretion of interferon γ (IFNγ), and interleukin-4 (IL-4) were measured by flow cytometry and ELISA. Patients with active disease had higher levels of plasma BAFF and BAFF mRNA than patients in remission and controls. In in vitro assays, rhBAFF promoted the survival of CD19+ and CD8+ cells, and increased the apoptosis of platelets and the secretion of IFN-γ. BR3-Fc successfully corrected the effects of rhBAFF on lymphocytes, platelets, and cytokines. These findings suggest that BAFF may play a pathogenic role in ITP by promoting the survival of CD19+ and CD8+ cells, and increasing the apoptosis of platelets and the secretion of IFN-γ. Blockade of BAFF by BR3-Fc might be a promising therapeutic approach for ITP.
In vivo intraclonal and interclonal kinetic heterogeneity in B-cell chronic lymphocytic leukemia
Authors: Calissano Carlo , Damle Rajendra N. , Hayes Gregory , Murphy Elizabeth J. , Hellerstein Marc K. , Moreno Carol , Sison Cristina , Kaufman Matthew S. , Kolitz Jonathan E. , Allen Steven L. , Rai Kanti R. , Chiorazzi Nicholas 
Published: September 2009

AbstractClonal evolution and outgrowth of cellular variants with additional chromosomal abnormalities are major causes of disease progression in chronic lymphocytic leukemia (CLL). Because new DNA lesions occur during S phase, proliferating cells are at the core of this problem. In this study, we used in vivo deuterium (2H) labeling of CLL cells to better understand the phenotype of proliferating cells in 13 leukemic clones. In each case, there was heterogeneity in cellular proliferation, with a higher fraction of newly produced CD38+ cells compared with CD38− counterparts. On average, there were 2-fold higher percentages of newly born cells in the CD38+ fraction than in CD38− cells; when analyzed on an individual patient basis, CD38+2H-labeled cells ranged from 6.6% to 73%. Based on distinct kinetic patterns, interclonal heterogeneity was also observed. Specifically, 4 patients exhibited a delayed appearance of newly produced CD38+ cells in the blood, higher leukemic cell CXC chemokine receptor 4 (CXCR4) levels, and increased risk for lymphoid organ infiltration and poor outcome. Our data refine the proliferative compartment in CLL based on CD38 expression and suggest a relationship between in vivo kinetics, expression of a protein involved in CLL cell retention and trafficking to solid tissues, and clinical outcome.
Modifiers of von Willebrand factor identified by natural variation in inbred strains of mice
Authors: Shavit Jordan A. , Manichaikul Ani , Lemmerhirt Heidi L. , Broman Karl W. , Ginsburg David 
Published: September 2009

AbstractType 1 von Willebrand disease (VWD) is the most common inherited human bleeding disorder. However, diagnosis is complicated by incomplete penetrance and variable expressivity, as well as wide variation in von Willebrand factor (VWF) levels among the normal population. Previous work has exploited the highly variable plasma VWF levels among inbred strains of mice to identify 2 major regulators, Mvwf1 and Mvwf2 (modifier of VWF). Mvwf1 is a glycosyltransferase and Mvwf2 is a natural variant in Vwf that alters biosynthesis. We report the identification of an additional alteration at the Vwf locus (Mvwf5), as well as 2 loci unlinked to Vwf (Mvwf6-7) using a backcross approach with the inbred mouse strains WSB/EiJ and C57BL/6J. Through positional cloning, we show that Mvwf5 is a cis-regulatory variant that alters Vwf mRNA expression. A similar mechanism could potentially explain a significant percentage of human VWD cases, especially those with no detectable mutation in the VWF coding sequence. Mvwf6 displays conservation of synteny with potential VWF modifier loci identified in human pedigrees, suggesting that its ortholog may modify VWF in human populations.
Di-(2 ethylhexyl) phthalate and flutamide alter gene expression in the testis of immature male rats
Authors: Vo Thuy TB , Jung Eui-Man , Dang Vu Hoang , Yoo Yeong-Min , Choi Kyung-Chul , Yu Frank H , Jeung Eui-Bae 
Published: September 2009

AbstractWe previously demonstrated that the androgenic and anti-androgenic effects of endocrine disruptors (EDs) alter reproductive function and exert distinct effects on developing male reproductive organs. To further investigate these effects, we used an immature rat model to examine the effects of di-(2 ethylhexyl) phthalate (DEHP) and flutamide (Flu) on the male reproductive system. Immature male SD rats were treated daily with DEHP and Flu on postnatal days (PNDs) 21 to 35, in a dose-dependent manner. As results, the weights of the testes, prostate, and seminal vesicle and anogenital distances (AGD) decreased significantly in response to high doses of DEHP or Flu. Testosterone (T) levels significantly decreased in all DEHP- treated groups, whereas luteinizing hormone (LH) plasma levels were not altered by any of the two treatments at PND 36. However, treatment with DEHP or Flu induced histopathological changes in the testes, wherein degeneration and disorders of Leydig cells, germ cells and dilatation of tubular lumen were observed in a dose-dependent manner. Conversely, hyperplasia and denseness of Leydig, Sertoli and germ cells were observed in rats given with high doses of Flu. The results by cDNA microarray analysis indicated that 1,272 genes were up-regulated by more than two-fold, and 1,969 genes were down-regulated in response to DEHP, Flu or both EDs. These genes were selected based on their markedly increased or decreased expression levels. These genes have been also classified on the basis of gene ontology (e.g., steroid hormone biosynthetic process, regulation of transcription, signal transduction, metabolic process, biosynthetic process...). Significant decreases in gene expression were observed in steroidogenic genes (i.e., Star, Cyp11a1 and Hsd3b). In addition, the expression of a common set of target genes, including CaBP1, Vav2, Plcd1, Lhx1 and Isoc1, was altered following exposure to EDs, suggesting that they may be marker genes to screen for the anti-androgenic or androgenic effects of EDs. Overall, our results demonstrated that exposure to DEHP, Flu or both EDs resulted in a alteration of gene expression in the testes of immature male rats. Furthermore, the toxicological effects of these EDs on the male reproductive system resulted from their anti-androgenic effects. Taken together, these results provide a new insight into the molecular mechanisms underlying the detrimental impacts of EDs, in regards to anti-androgenic effects in humans and wildlife.
Effect of age at onset of schizophrenia on white matter abnormalities
Authors: Kyriakopoulos Marinos , Perez-Iglesias Rocio , Woolley James B. , Kanaan Richard A. A. , Vyas Nora S. , Barker Gareth J. , Frangou Sophia , McGuire Philip K. 
Published: September 2009

BackgroundThe pattern of brain morphological changes at the early stages of schizophrenia may depend on the age at onset of illness; in children and adolescents with schizophrenia, grey matter deficits are seen in the parietal lobe whereas in individuals with adult onset these are more widespread.AimsTo examine whether white matter is similarly affected.MethodDiffusion tensor imaging was used to compare fractional anisotropy measures in individuals with adolescent-onset (n = 17) and adult-onset schizophrenia (n = 17) with those in age- and gender-matched controls.ResultsCompared with their respective controls, individuals with adolescent-onset schizophrenia showed fractional anisotropy decrease in parietal regions; individuals with adult onset showed additional fractional anisotropy reductions in frontal, temporal and cerebellar regions. A differential effect of age at onset (adolescent v. adult) was noted bilaterally in medial prefrontal white matter.ConclusionsWhite matter abnormalities in frontal regions in schizophrenia may depend on developmental stage at the time of illness onset.
Neuropsychological functioning in first-episode schizophrenia
Authors: Kravariti Eugenia , Morgan Kevin , Fearon Paul , Zanelli Jolanta W. , Lappin Julia M. , Dazzan Paola , Morgan Craig , Doody Gillian A. , Harrison Glynn , Jones Peter B. , Murray Robin M. , Reichenberg Abraham 
Published: September 2009

BackgroundIdentifying neurocognitive subtypes in schizophrenia may help establish neurobiologically meaningful subtypes of the disorder, but is frequently confounded by differences in intellectual function between individuals with schizophrenia and controls.AimsTo examine neuropsychological performance in individuals with epidemiologically based, first-onset schizophrenia and intellectually matched controls.MethodUsing standard IQ and reading tests, we examined the proportions of 101 people with epidemiologically derived, first-onset schizophrenia/schizoaffective disorder and 317 community controls, falling into three a priori defined intellectual categories: ‘stable good’, ‘deteriorated poor’ and ‘stable poor’. Neuropsychological function was compared between intellectually matched participants with schizophrenia and control subgroups.ResultsMultiple deficits in executive function, processing speed and verbal memory, but not visual/spatial perception/memory, were detected in all participant groups with schizophrenia compared with controls. The average effect size across the affected domains ranged from small to medium to large in the stable good, deteriorated poor and stable poor subgroups of participants with schizophrenia, respectively.ConclusionsCompared with intellectually matched controls, people with epidemiologically derived, first-onset schizophrenia/schizoaffective disorder show multiple deficits in executive function, processing speed and verbal memory.
Long-term effectiveness of a parenting intervention for children at risk of developing conduct disorder
Authors: Bywater Tracey , Hutchings Judy , Daley David , Whitaker Chris , Yeo Seow Tien , Jones Karen , Eames Catrin , Edwards Rhiannon Tudor 
Published: September 2009

BackgroundThe typical pattern for intervention outcome studies for conduct problems has been for effect sizes to dissipate over time with decreasing effects across subsequent follow-ups.AimsTo establish whether the short-term positive effects of a parenting programme are sustained longer term. To observe trends, and costs, in health and social service use after intervention.MethodParents with children aged 36–59 months at risk of developing conduct disorder (n = 104) received intervention between baseline and first follow-up (6 months after baseline n = 86) in 11 Sure Start areas in North Wales. Follow-ups two (n = 82) and three (n = 79) occurred 12 and 18 months after baseline. Child problem behaviour and parenting skills were assessed via parent self-report and direct observation in the home.ResultsThe significant parent-reported improvements in primary measures of child behaviour, parent behaviour, parental stress and depression gained at follow-up one were maintained to follow-up three, as were improved observed child and parent behaviours. Overall, 63% of children made a minimum significant change (0.3 standard deviations) on the Eyberg Child Behavior Inventory problem scale between baseline and follow-up (using intention-to-treat data), 54% made a large change (0.8 standard deviations) and 39% made a very large change (1.5 standard deviations). Child contact with health and social services had reduced at follow-up three.ConclusionsEarly parent-based intervention reduced child antisocial behaviour and benefits were maintained, with reduced reliance on health and social service provision, over time.
Cost-effectiveness of a primary care model for anxiety disorders
Authors: König Hans-Helmut , Born Anja , Heider Dirk , Matschinger Herbert , Heinrich Sven , Riedel-Heller Steffi G. , Surall Daniel , Angermeyer Matthias C. , Roick Christiane 
Published: September 2009

BackgroundIndividuals with anxiety disorders often do not receive an accurate diagnosis or adequate treatment in primary care.AimsTo analyse the cost-effectiveness of an optimised care model for people with anxiety disorders in primary care.MethodIn a cluster randomised controlled trial, 46 primary care practices with 389 individuals positively screened with anxiety were randomised to intervention (23 practices, 201 participants) or usual care (23 practices, 188 participants). Physicians in the intervention group received training on diagnosis and treatment of anxiety disorders combined with the offer of a psychiatric consultation–liaison service for 6 months. Anxiety, depression, quality of life, service utilisation and costs were assessed at baseline, 6-month and 9-month follow-up.ResultsResultsNo significant differences were observed between intervention and control group on the Beck Anxiety Inventory, Beck Depression Inventory and EQ–5D during follow-up. Total costs were higher in the intervention group (€4911v.€3453,P= 0.09). The probability of an incremental cost-effectiveness ratio <€50 000 per quality-adjusted life year was below 10%.ConclusionsThe optimised care model did not prove to be cost-effective.
Psychiatric disorders and other health dimensions among Holocaust survivors 6 decades later
Authors: Sharon Asaf , Levav Itzhak , Brodsky Jenny , Shemesh Annarosa Anat , Kohn Robert 
Published: September 2009

BackgroundNo previous community-based epidemiological study has explored psychiatric disorders among those who survived the Holocaust.AimsTo examine anxiety and depressive disorders, sleep disturbances, other health problems and use of services among individuals exposed and unexposed to the Holocaust.MethodThe relevant population samples were part of the Israel World Mental Health Survey. The interview schedule included the Composite International Diagnostic Interview and other health-related items.ResultsThe Holocaust survivor group had higher lifetime (16.1%; OR = 6.8, 95% CI 1.9–24.2) and 12-month (6.9%; OR = 22.5, 95% CI 2.5–204.8) prevalence rates of anxiety disorders, and more current sleep disturbances (62.4%; OR = 2.5, 95% CI 1.4–4.4) and emotional distress (P<0.001) than their counterparts, but did not have higher rates of depressive disorders or post-traumatic stress disorder.ConclusionsEarly severe adversity was associated with psychopathological disorder long after the end of the Second World War, but not in all survivors. Age during the Holocaust did not modify the results.
Structure of genetic and environmental risk factors for dimensional representations of DSM–IV anxiety disorders
Authors: Tambs Kristian , Czajkowsky Nikolai , R⊘ysamb Espen , Neale Michael C. , Reichborn-Kjennerud Ted , Aggen Steven H. , Harris Jennifer R. , ⊘rstavik Ragnhild E. , Kendler Kenneth S. 
Published: September 2009

BackgroundTwin data permit decomposition of comorbidity into genetically and environmentally derived correlations. No previous twin study includes all major forms of anxiety disorder.AimsTo estimate the degree to which genetic and environmental risk factors are shared rather than unique to dimensionally scored panic disorder, generalised anxiety disorder, phobias, obsessive–compulsive disorder and post-traumatic stress disorder.MethodData obtained from 2801 young-adult Norwegian twins by means of the Composite International Diagnostic Interview were analysed with the Mx program.ResultsA multivariate common factor model fitted best. The latent liability to all anxiety disorders was substantially more heritable (54%) than the individual disorders (23% to 40%). Most of the genetic effect was common to the disorders. Genes contributed just over 50% to the covariance between liabilities.ConclusionsThe five anxiety disorders all share genetic and environmental risk factors. This has implications for the revision of the anxiety disorder section in DSM–V.
Confectionery consumption in childhood and adult violence
Authors: Moore Simon C. , Carter Lisa M. , van Goozen Stephanie H. M. 
Published: September 2009

SummaryDiet has been associated with behavioural problems, including aggression, but the long-term effects of childhood diet on adult violence have not been studied. We tested the hypothesis that excessive consumption of confectionery at age 10 years predicts convictions for violence in adulthood (age 34 years). Data from age 5, 10 and 34 years were used. Children who ate confectionery daily at age 10 years were significantly more likely to have been convicted for violence at age 34 years, a relationship that was robust when controlling for ecological and individual factors.
Invited commentary on … Mental health research priorities in low- and middle-income countries
Authors: Araya Ricardo 
Published: September 2009

SummaryThere are huge inequalities in health research within and between countries. It is argued that this may hinder the process of setting and tackling mental health priorities. If this were true, establishing research priorities would be important. However, this is not a simple process and one must be aware of its limitations. Despite a plethora of declarations, funding for mental health research in low- and middle-income countries remains hard to find. In the absence of funding, establishing research priorities is seen by many as an exercise of lesser importance.
Do we know the legal framework in child and adolescent mental health services? Survey of specialist registrars
Authors: Khan Faeza , Khan Faria , Hackett Latha , Ross Kenneth 
Published: September 2009

Aims and MethodThis survey was conducted as part of the baseline assessment of trainees' needs concerning the legal aspects of child care and to evaluate the implications for the regional academic programme. A group of specialist registrars in child and adolescent psychiatry in the North Western Deanery completed a questionnaire-based survey.ResultsNone of the specialist registrars had experience in forensic child and adolescent psychiatry. With regard to the legislation: 13 (100%) mentioned the Mental Health Act 1983; 12 (92.3%) the Children Act 1989; 7 (53.8%) the Human Rights Act 1998. of those surveyed, 13 (100%) were aware of parental responsibility; 10 (76.9%) identified the Children Act as being less stigmatising as compared to the Mental Health Act. Five (38.4%) had written court reports, and eight (61.5%) felt fairly confident after the 1-day training course. Overall interest in becoming an expert witness was 69.2% (n=9).Clinical ImplicationsDeficits in knowledge about the legal framework, limited experience in forensic placements and lack of interest in becoming an expert witness need to be further explored.