Miracle-dz/UniFAR-FTUs huggingface dataset:
Aquaporin-4 antibody in neuromyelitis optica: re-testing study in a large population from China

ABSTRACT Background: Aquaporin-4 (AQP4) antibody sero-positivity is critically important in neuromyelitis optica (NMO). However, the sensitivity of different assays is highly variable. Repeating detection with a highly sensitive assay in a large population is necessary in the case of so-called negative NMO. Methods: Retrospective analysis where AQP4 antibodies were detected by commercial cell-based assay (CBA), in-house M23-CBA and in-house M1-CBA. Results: Of the 1011 serum samples, 206 (20.4%) were sero-positive by primary commercial CBA. In the retest, all 206 participants positive by primary commercial CBA also yielded positive results by in-house M23-CBA and the second commercial CBA again, but only 124 positive in in-house M1-CBA. Among the 805 participants negative by primary commercial CBA, 71 participants were positive for in-house M23-CBA, of which 20 participants were positive for the second commercial CBA, and none were positive by in-house M1-CBA. Of the 171 cerebral spinal fluid samples, 75 (43.9%) were positive by primary commercial CBA. All 75 participants positive by primary commercial CBA also yielded positive results by in-house M23-CBA and the second commercial CBA. Forty-nine (65.3%) of these 75 participants were positive by in-house M1-CBA. Among the 96 participants negative by primary commercial CBA, 15 participants were positive for in-house M23-CBA and none were positive by in-house M1-CBA and the second commercial CBA. Conclusions: Different AQP4 isoforms in CBA result in different detection effects, and in-house M23-CBA is the most sensitive method. Some AQP4 antibody–negative NMO may be subject to diagnostic uncertainty due to limitations of the assays.
Mycobacterium abscessus in cystic fibrosis lung transplant recipients: report of 2 cases and risk for recurrence

Abstract: Mycobacterium abscessus is increasingly recognized as an important pathogen in some individuals with advancing lung disease related to cystic fibrosis (CF). Because of its resistance to antimicrobial agents and virulence, its presence in the lungs of potential lung transplant recipients can be problematic. We present 2 cases of individuals with CF in whom M. abscessus was present in the preoperative sputum cultures. The organism manifested different degrees of invasiveness in the 2 cases after transplantation with different outcomes, suggesting an approach to future candidates for lung transplantation that may be of clinical significance to their physicians and surgeons.
MLN3897 plus methotrexate in patients with rheumatoid arthritis: safety, efficacy, pharmacokinetics, and pharmacodynamics of an oral CCR1 antagonist in a phase IIa, double-blind, placebo-controlled, randomized, proof-of-concept study.

OBJECTIVE To assess the efficacy, safety, pharmacokinetics, and pharmacodynamics of the CC chemokine receptor CCR1 antagonist MLN3897 in patients with rheumatoid arthritis (RA) receiving methotrexate (MTX). METHODS In this phase IIa, proof-of-concept study, patients meeting the American College of Rheumatology (ACR) criteria for RA who had been taking MTX for >or=6 months with evidence of active disease were randomly assigned to receive either 10 mg oral MLN3897 or matching placebo once daily for 12 weeks (days 1-83) while continuing to receive MTX once a week. Clinical assessments, safety monitoring, and sampling for pharmacokinetic and pharmacodynamic analyses were performed throughout the study. The primary efficacy end point was the difference in the percentage of patients meeting the ACR 20% improvement criteria (achieving an ACR20 response) on day 84 in the MLN3897-treated group compared with that in the placebo-treated group. RESULTS MLN3897 was well tolerated, with no evidence of systemic immunosuppression. In the intent-to-treat population, there was no significant difference in day 84 ACR20 response rates between MLN3897-treated patients and placebo-treated patients (35% versus 33%, respectively; P=0.72). Results were similar for the per-protocol population. Pharmacokinetic analyses demonstrated no interactions between MLN3897 and MTX. MLN3897 was associated with a high degree of CCR1 occupancy (>or=90% on days 28, 56, and 84 in 82% of patients, by macrophage inflammatory protein 1alpha internalization assay). CONCLUSION MLN3897 at a concentration of 10 mg once daily had no discernible activity in patients with RA who were also receiving MTX. The results suggest that CCR1 antagonism is unlikely to be a viable strategy for the treatment of RA when used in isolation at the receptor occupancy levels reached in this study.
Humoral responses after influenza vaccination are severely reduced in patients with rheumatoid arthritis treated with rituximab.

OBJECTIVE For patients with rheumatoid arthritis (RA), yearly influenza vaccination is recommended. However, its efficacy in patients treated with rituximab is unknown. The objectives of this study were to investigate the efficacy of influenza vaccination in RA patients treated with rituximab and to investigate the duration of the possible suppression of the humoral immune response following rituximab treatment. We also undertook to assess the safety of influenza vaccination and the effects of previous influenza vaccination. METHODS Trivalent influenza subunit vaccine was administered to 23 RA patients who had received rituximab (4-8 weeks after rituximab for 11 patients [the early rituximab subgroup] and 6-10 months after rituximab for 12 patients [the late rituximab subgroup]), 20 RA patients receiving methotrexate (MTX), and 29 healthy controls. Levels of antibodies against the 3 vaccine strains were measured before and 28 days after vaccination using hemagglutination inhibition assay. The Disease Activity Score in 28 joints (DAS28) was used to assess RA activity. RESULTS Following vaccination, geometric mean titers (GMTs) of antiinfluenza antibodies significantly increased for all influenza strains in the MTX-treated group and in healthy controls, but for no strains in the rituximab-treated group. However, in the late rituximab subgroup, a rise in GMT for the A/H3N2 and A/H1N1 strains was demonstrated, in the absence of a repopulation of CD19+ cells at the time of vaccination. Seroconversion and seroprotection occurred less often in the rituximab-treated group than in the MTX-treated group for the A/H3N2 and A/H1N1 strains, while seroprotection occurred less often in the rituximab-treated group than in the healthy controls for the A/H1N1 strain. Compared with unvaccinated patients in the rituximab-treated group, previously vaccinated patients in the rituximab-treated group had higher pre- and postvaccination GMTs for the A/H1N1 strain. The DAS28 did not change after vaccination. CONCLUSION Rituximab reduces humoral responses following influenza vaccination in RA patients, with a modestly restored response 6-10 months after rituximab administration. Previous influenza vaccination in rituximab-treated patients increases pre- and postvaccination titers. RA activity was not influenced.
Lower incidence of cytomegalovirus infection with everolimus versus mycophenolate mofetil in de novo cardiac transplant recipients: a randomized, multicenter study

M. Viganò, T. Dengler, M.F. Mattei, A. Poncelet, J. Vanhaecke, E. Vermes, R. Kleinloog, Y. Li, Y. Gezahegen, J.F. Delgado, on behalf of the RAD A2411 Study Investigators. Lower incidence of cytomegalovirus infection with everolimus versus mycophenolate mofetil in de novo cardiac transplant recipients: a randomized, multicenter study. Transpl Infect Dis 2010: 12: 23–30. All rights reserved
Genetic variation at the IRF7/PHRF1 locus is associated with autoantibody profile and serum interferon-alpha activity in lupus patients.

OBJECTIVE Interferon-alpha (IFNalpha) is a heritable risk factor for systemic lupus erythematosus (SLE). Genetic variation near IRF7 is implicated in SLE susceptibility. SLE-associated autoantibodies can stimulate IFNalpha production through the Toll-like receptor/IRF7 pathway. This study was undertaken to determine whether variants of IRF7 act as risk factors for SLE by increasing IFNalpha production and whether autoantibodies are important to this phenomenon. METHODS We studied 492 patients with SLE (236 African American, 162 European American, and 94 Hispanic American subjects). Serum levels of IFNalpha were measured using a reporter cell assay, and single-nucleotide polymorphisms (SNPs) in the IRF7/PHRF1 locus were genotyped. RESULTS In a joint analysis of European American and Hispanic American subjects, the rs702966 C allele was associated with the presence of anti-double-stranded DNA (anti-dsDNA) antibodies (odds ratio [OR] 1.83, P = 0.0069). The rs702966 CC genotype was only associated with higher serum levels of IFNalpha in European American and Hispanic American patients with anti-dsDNA antibodies (joint analysis P = 4.1 x 10(-5) in anti-dsDNA-positive patients and P = 0.99 in anti-dsDNA-negative patients). In African American subjects, anti-Sm antibodies were associated with the rs4963128 SNP near IRF7 (OR 1.95, P = 0.0017). The rs4963128 CT and TT genotypes were associated with higher serum levels of IFNalpha only in African American patients with anti-Sm antibodies (P = 0.0012). In African American patients lacking anti-Sm antibodies, an effect of anti-dsDNA-rs702966 C allele interaction on serum levels of IFNalpha was observed, similar to the other patient groups (overall joint analysis P = 1.0 x 10(-6)). In European American and Hispanic American patients, the IRF5 SLE risk haplotype showed an additive effect with the rs702966 C allele on IFNalpha level in anti-dsDNA-positive patients. CONCLUSION Our findings indicate that IRF7/PHRF1 variants in combination with SLE-associated autoantibodies result in higher serum levels of IFNalpha, providing a biologic relevance for this locus at the protein level in human SLE in vivo.
PSYCHIC TRAUMA OF OPERATIONS IN CHILDREN: AND A NOTE ON COMBAT NEUROSIS

Impressed by the number of cases in which fears, anxieties and other symptoms closely followed an operative procedure, I reviewed my records for some years past in order to determine how frequently such difficulties arose. The findings are given in table 1. Only such patients as revealed manifest symptoms are included. Certain patients in whom it appeared that after. an operation some anxiety remained to flare up into acute symptoms later are considered separately (see Reports of Cases, section B). All operative procedures, regardless of form, are included in table 1. They include inoculations, treatments of small cuts and the like. However, the vast majority of operations were tonsillectomies. Only first operative procedures are included. 1 The effects of cumulative operations are given in the appended case studies. No major operative procedures were recorded for the group under 12 months of age, and evidently the vaccinations and inoculations given in
Electroconvulsive Therapy: Part II: A Biopsychosocial Perspective

The myths surrounding electroconvulsive therapy (ECT) and the misconceptions held by the general public, clinicians, and patients have interfered with acceptance of this treatment throughout its history. Misunderstandings surrounding ECT, and its consequent stigmatization, are reviewed, including negative depictions of ECT in film, print media, and on the Internet. Clinicians involved in the delivery of ECT benefit from gaining an understanding of how ECT may be perceived by patients and other mental health professionals; they can play a vital role in educating patients and helping ensure the delivery of a successful course of ECT. Guidance is provided for clinicians on how to support patients and families through the ECT process using a model team approach. Anxiety reduction, meeting individual needs, patient and family psychoeducation, assessment of psychosocial supports, and discharge planning are discussed.
Hatha Yoga for Depression: Critical Review of the Evidence for Efficacy, Plausible Mechanisms of Action, and Directions for Future Research

Background The purpose of this article is to review the evidence for the efficacy of hatha yoga for depression and possible mechanisms by which yoga may have an impact on depression, and to outline directions for future research. Methods Literature review and synthesis. Results and Conclusions A literature search for clinical trials examining yoga for depression uncovered eight trials: 5 including individuals with clinical depression, and 3 for individuals with elevated depression symptoms. Although results from these trials are encouraging, they should be viewed as very preliminary because the trials, as a group, suffered from substantial methodological limitations. We would argue, however, that there are several reasons to consider constructing careful research on yoga for depression. First, current strategies for treating depression are not sufficient for many individuals, and patients have several concerns about existing treatments. Yoga may be an attractive alternative to or a good way to augment current depression treatment strategies. Second, aspects of yoga—including mindfulness promotion and exercise—are thought to be “active ingredients” of other successful treatments for depression. Third, there are plausible biological, psychological, and behavioral mechanisms by which yoga may have an impact on depression. We provide suggestions for the next steps in the study of yoga as a treatment for depression. (Journal of Psychiatric Practice 2010;16:22–33).
Dynamic order acceptance and capacity planning in a stochastic multi-project environment with a bottleneck resource

We study the integration of order acceptance and capacity planning in multi-project environments with dynamically arriving projects. We model this planning problem as a continuous-time Markov decision process to determine long-term optimal decisions. We examine whether macro-process planning should be performed before or after order acceptance. We characterise the structure of optimal policies, and explore the dependence on a number of parameters such as project payoff, project cost and order arrival time. We also look into the effects of set-up costs and the use of non-regular capacity.
Transmisión sináptica-canales de calcio y liberación de neurotransmisores

La comunicacion neuronal en el sistema nervioso esta mediada, en la gran mayoria de animales, por la transmision sinaptica quimica. Generalmente esta comunicacion ocurre mediante la liberacion de una sustancia transmisora en el terminal presinaptico. Este transmisor sinaptico se une a receptores postsinapticos y da lugar a una respuesta postsinaptica en la celula blanco. La liberacion del transmisor en la region presinaptica, al parecer, es desencadenada por un aumento transitorio del calcio intracelular en el sitio de liberacion. Este aumento se logra, principalmente, por la activacion de canales de calcio dependientes de voltaje (VGCC), lo que da lugar a un ingreso de iones de calcio en el citosol presinaptico, que desencadena la fusion de las vesiculas sinapticas y la liberacion del neurotransmisor. En este articulo se revisan las caracteristicas moleculares y funcionales de los VGCC necesarias para la comprension de alteraciones patologicas como las canalopatias y la transmision sinaptica anormal. Metodologia: se consultaron las bases de datos Medline, Pubmed y los e-journals de la Biblioteca de la Universidad de Columbia, correspondientes a los anos 1990 a 2004. Resultados: durante la ultima decada se han logrado avances significativos en los aspectos moleculares y en la genetica de los canales dependientes de voltaje. La integracion de este conocimiento con la neurofisiologia funcional y la neurologia clinica apenas se esta iniciando.
Learning from Losing: Ethical, Psychoanalytic, and Spiritual Perspectives on Managing the Incremental Losses of the Distributed Self in Dementia

The author describes his experiences making decisions about the care of his mother, who was suffering from dementia, and the profound effect this process had on him as a psychotherapist. As background, he first presents an overview of writings from Jerry M. Lewis, George Pollock, and George Vaillant on issues related to attachment, death, loss, and mourning. The author equates his experiences caring for his mother with a type of involuntary “continuing education” and describes the lessons he learned as he was faced with decisions about his mother's level of care and as he mourned the slow, piecemeal loss of her distributed self. A case vignette is presented to illustrate how the author applied the lessons he had learned in psychotherapy with a distressed patient caring for her aging mother. The article concludes with a summary of the clinical and ethical questions raised by this case and the author's experience with his mother and a discussion of principles that can help psychotherapists provide treatment for patients who are caring for family members with dementia. (Journal of Psychiatric Practice. 2011;17:41–48).
Two children with differing outcomes after treatment for pulmonary tuberculosis diagnosed after allogeneic hematopoietic stem cell transplantation

J.W. Lee, H. ‐J. Kwon, P.‐S. Jang, N. ‐G. Chung, B. Cho, D. ‐C. Jeong, J.‐H. Kang, H. ‐K. Kim. Two children with differing outcomes after treatment for pulmonary tuberculosis diagnosed after allogeneic hematopoietic stem cell transplantation. Transpl Infect Dis 2011: 13: 520–523. All rights reserved.
Golimumab, a new human anti-tumor necrosis factor alpha antibody, administered intravenously in patients with active rheumatoid arthritis: Forty-eight-week efficacy and safety results of a phase III randomized, double-blind, placebo-controlled study.

OBJECTIVE To assess the efficacy and safety of intravenous administration of golimumab in patients with rheumatoid arthritis (RA). METHODS Adult patients with RA in whom disease activity was persistent despite treatment with methotrexate (MTX) at a dosage of 15-25 mg/week for > or = 4 weeks were randomized to receive intravenous infusions of placebo plus MTX or intravenous infusions of golimumab at a dose of 2 mg/kg or 4 mg/kg, with or without MTX, every 12 weeks through week 48. Patients with <20% improvement in the swollen and tender joint counts could enter early escape and receive additional active treatment (week 16) or could have their dose regimen adjusted (week 24). The primary end point was the proportion of patients achieving a 50% response according to the American College of Rheumatology improvement criteria (ACR50) at week 14. RESULTS The primary study end point was not met (at week 14, an ACR50 response was observed in 21% of the patients treated with golimumab plus MTX compared with 13% of the patients treated with placebo plus MTX [P = 0.051]). By week 24, significantly more patients treated with golimumab plus MTX had achieved an ACR50 response. Differences in the proportion of patients achieving an ACR50 response between the group receiving golimumab monotherapy and the group receiving placebo plus MTX were not significant at either week 14 (16% versus 13%) or week 24 (10% versus 9%). At week 48, the proportions of patients achieving ACR20 and ACR50 responses were highest among those who had received golimumab 4 mg/kg plus MTX (70% and 48%, respectively). Concomitant treatment with MTX was associated with a lower incidence of antibodies to golimumab. The most commonly reported adverse events through week 48 were infections (48% of patients treated with golimumab with or without MTX and 41% of patients receiving placebo plus MTX). CONCLUSION The primary end point was not met. However, intravenously administered golimumab plus MTX appears to have benefit in the longer-term reduction of RA signs/symptoms in MTX-resistant patients, with no unexpected safety concerns.
Different response to rituximab in tumor necrosis factor blocker-naive patients with active ankylosing spondylitis and in patients in whom tumor necrosis factor blockers have failed: a twenty-four-week clinical trial.

OBJECTIVE Histologic studies have shown B cell clusters in the subchondral bone marrow of the spine of patients with ankylosing spondylitis (AS). An immunotherapy targeting B cells in AS is therefore of interest. We undertook this study to examine the efficacy and safety of rituximab in patients with AS refractory to nonsteroidal antiinflammatory drugs in whom previous treatment with tumor necrosis factor alpha (TNFalpha) blockers either had not been tried or had failed. METHODS In this phase II clinical trial, 1,000 mg rituximab was administered intravenously at baseline and at week 2 in 20 patients with active AS. Ten of these patients had never received TNF blockers, and treatment with TNF blockers had failed in the other 10 patients. The primary end point was a 20% improvement in disease activity at week 24 according to the criteria of the Assessment of SpondyloArthritis international Society (an ASAS20 response). RESULTS Seventy-five percent of the patients were male, 90% were HLA-B27 positive, their mean age was 39.7 years, and their mean disease duration was 16.8 years. Patients had active disease, defined as a Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) score >or=4. While there was no clear response at week 24 in the group in whom TNF blockers had failed (30% had achieved an ASAS20 response, 10% had achieved an ASAS40 response, none had achieved partial remission according to the ASAS criteria, and none had achieved 50% improvement on the BASDAI [a BASDAI50 response] beyond an expected placebo response), we observed a good improvement in the TNF blocker-naive group at week 24 (50% had achieved an ASAS20 response, 40% had achieved an ASAS40 response, 30% had achieved partial remission according to the ASAS criteria, and 50% had achieved a BASDAI50 response). CONCLUSION Although rituximab does not seem to be effective in patients with AS that does not respond to TNF blockers, it had significant efficacy in TNF blocker-naive patients. Therefore, further controlled trials with B cell-directed therapies should be performed in TNF blocker-naive AS patients in the future.
P2-479 Determinants of functioning and disability in aged persons: results from the KORA-Age Study

Introduction Increasing attention is paid on functioning and disability as determinants of autonomy and independent living in aged persons. Yet, determinants of functioning and disability have not been studied extensively in this age group. Most studies took a disease-oriented approach by investigating populations with specific health conditions. So far, few representative findings on the prevalence of disability and its determinants in aged persons are available. The objective of our study is to examine distribution and determinants of functioning and disability in aged persons in the community. Methods The data originate from the MONICA/KORA study, a population-based cohort study established in 1984 in Germany. Survivors of the original cohorts aged 65 years and above were examined from 01/2009 to 12/2009. Disability was assessed with the Health Assessment Questionnaire. Logistic regression was used to estimate raw effects and conditional inference trees with Bonferroni adjusted p-values were used to identify high risk groups. Results We analysed a total of 4127 individuals (51.2% female) with a mean age of 73.3 years (SD=6.1). Disability was present in 44.7% of all individuals (54% for women, 35% for men). Prevalence of disability increased from 28.8% for 65–70 year old individuals to 75.9% for individuals over 80. Prevalence was 31.6% in individuals without comorbidity, else 55.9% (RR=1.77). High risk groups were found among all age groups. Conclusion Minimal disability is highly prevalent in aged persons. The results give a representative overview of the prevalence and determinants of disability in the aged in the German population.