Novel conformation-selective alpha-synuclein antibodies raised against different in vitro fibril forms show distinct patterns of Lewy pathology in Parkinson's disease.

AIMS: The aim of this study was to test the hypothesis that different conformations of misfolded α-synuclein (α-syn) are present in Parkinson's disease (PD) brain. METHODS: Using two previously characterized conformations of α-syn fibrils, we generated new conformation-selective α-syn monoclonal antibodies (mAbs). We then interrogated multiple brain regions in a well-characterized autopsy cohort of PD patients (n = 49) with these mAbs, Syn7015 and Syn9029. RESULTS: Syn7015 detects Lewy bodies (LBs) and Lewy neurites (LNs) formed by pathological α-syn in all brain regions tested, and is particularly sensitive to LNs and small Lewy dots, inclusions believed to form early in the disease. Further, we observed colocalization between Syn7015 and an early marker of α-syn pathology formation, phospho-Ser129-α-syn, and a lack of extensive colocalization with markers of more mature pathology. In comparison, Syn9029 detects Lewy pathology in all regions examined, but indicates significantly fewer LNs than Syn7015. In addition, colocalization of Syn9029 with later markers of α-syn pathology maturation (ubiquitin and P62) suggests that the pathology detected by Syn9029 is older. Semiquantitative scoring of both LN and LB pathology in nine brain regions further established this trend, with Syn7015 LN scores consistently higher than Syn9029 LN scores. CONCLUSIONS: Our data indicate that different conformations of α-syn pathology are present in PD brain and correspond to different stages of maturity for Lewy pathology. Regional analysis of Syn7015 and Syn9029 immunostaining also provides support for the Braak hypothesis that α-syn pathology advances through the brain.

The role of calcium in health and disease.

Skeletal fragility at the end of the life span (osteoporosis) is a major source of morbidity and mortality. Adequate calcium intake from childhood to the end of the life span is critical for the formation and retention of a healthy skeleton. High intakes of calcium and vitamin D potentiate the bone loss prevention effects of hormone replacement therapy in postmenopausal women. Pregnancy and lactation are not risk factors for skeletal fragility, although lactation is associated with a transient loss of bone that cannot be prevented by calcium supplementation. Low calcium intake has been implicated in the development of hypertension, colon cancer, and premenstrual syndrome, and it is associated with low intakes of many other nutrients. Encouragement of increased consumption of calcium-rich foods has the potential to be a cost-effective strategy for reducing fracture incidence later in life and for increasing patients' dietary quality and overall health.

Accuracy of data in abstracts of published research articles.

CONTEXT: The section of a research article most likely to be read is the abstract, and therefore it is particularly important that the abstract reflect the article faithfully. OBJECTIVE: To assess abstracts accompanying research articles published in 6 medical journals with respect to whether data in the abstract could be verified in the article itself. DESIGN: Analysis of simple random samples of 44 articles and their accompanying abstracts published during 1 year(July 1, 1996-June 30, 1997) in each of 5 major general medical journals (Annals of Internal Medicine, BMJ, JAMA, Lancet, and New England Journal of Medicine) and a consecutive sample of 44 articles published during 15 months (July 1, 1996-August 15, 1997) in the CMAJ. MAIN OUTCOME MEASURE: Abstracts were considered deficient if they contained data that were either inconsistent with corresponding data in the article's body (including tables and figures) or not found in the body at all. RESULTS: The proportion of deficient abstracts varied widely (18%-68%) and to a statistically significant degree (P<.001) among the 6 journals studied. CONCLUSIONS: Data in the abstract that are inconsistent with or absent from the article's body are common, even in large-circulation general medical journals.

Can the accuracy of abstracts be improved by providing specific instructions? A randomized controlled trial.

CONTEXT: The most-read section of a research article is the abstract, and therefore it is especially important that the abstract be accurate. OBJECTIVE: To test the hypothesis that providing authors with specific instructions about abstract accuracy will result in improved accuracy. DESIGN: Randomized controlled trial of an educational intervention specifying 3 types of common defects in abstracts of articles that had been reviewed and were being returned to the authors with an invitation to revise. MEAN OUTCOME MEASURE: Proportion of abstracts containing 1 or more of the following defects: inconsistency in data between abstract and body of manuscript (text, tables, and figures), data or other information given in abstract but not in body, and/or conclusions not justified by information in the abstract. RESULTS: Of 250 manuscripts randomized, 13 were never revised and 34 were lost to follow-up, leaving a final comparison between 89 in the intervention group and 114 in the control group. Abstracts were defective in 25 (28%) and 30 (26%) cases, respectively (P=.78). Among 55 defective abstracts, 28 (51%) had inconsistencies, 16 (29%) contained data not present in the body, 8 (15%) had both types of defects, and 3 (5%) contained unjustified conclusions. CONCLUSIONS: Defects in abstracts, particularly inconsistencies between abstract and body and the presentation of data in abstract but not in body, occur frequently. Specific instructions to authors who are revising their manuscripts are ineffective in lowering this rate. Journals should include in their editing processes specific and detailed attention to abstracts.

Ethical and quasi-ethical issues in medical editing and publishing.

The peer review system is a complex, delicately balanced, and dynamic system by which most new medical information is made known. The participants in the process - authors, reviewers, and editors - all have responsibilities to shoulder and rights that need to be protected. An ethical structure has evolved over time to accomplish these two goals. This paper discusses six of these ethical or quasi-ethical issues. Authorship is currently a contentious matter, in part because authors see it as a credit, whereas editors view it as responsibility. Conflict of interest, usually financial, which seems to be increasing with the growing commercialization of medicine, can undermine the credibility and integrity of publication. Confidentiality is an essential component of peer review to protect an author's creative work from exploitation or misappropriation and to protect reviewers from retribution. Redundant publication, publishing or attempting to publish essentially the same work more than once, is regarded seriously because it wastes a journal's resources, confuses later literature reviews, and depreciates the value of authorship. Advertising is a necessary fact of life for most medical journals, but safeguards must be in place to prevent its influencing editorial decisions. When fraud or plagiarism is alleged about something a journal has published, the journal is not equipped to undertake the kind of investigation needed, and should refer the matter to the institution that sponsored the research.

Endocervical sampling by Kevorkian curette or Pipelle aspiration device: a randomized comparison.

OBJECTIVE: Our purpose was to compare two means of endocervical sampling-the Kevorkian curette and the Pipelle aspiration device (Unimar Co., Wilton, Conn.)-with respect to patient discomfort, tissue volume, and specimen adequacy for diagnosis. STUDY DESIGN: Fifty-two women undergoing investigation of abnormal cervical cytologic results were assigned randomly to endocervical sampling by Kevorkian or Pipelle instruments. Pain associated with the procedure was assessed by having each subject indicate her pain level on a visual analog scale. Tissue volume was graded by examination of the microscopic slides by two investigators blinded to assignment. Adequacy for diagnosis was evaluated by reviewing pathology reports. RESULTS: Subjects having Pipelle endocervical aspiration (n = 24) had significantly lower mean (+/- SEM) pain scores (27 +/- 5 vs 48.5 +/- 7, p = 0.02) than those in whom the Kevorkian instrument was used (n = 28). However, there were no significant differences in tissue volume obtained or in proportions considered adequate for diagnosis. CONCLUSIONS: Use of the Pipelle instrument was associated with less patient discomfort than Kevorkian curettage for endocervical sampling while providing similar tissue volume and adequacy for diagnosis.