Direction determination in the minus-end-directed kinesin motor ncd

Motor proteins of the kinesin superfamily transport intracellular cargo along microtubules. Although different kinesin proteins share 30-50% amino-acid identity in their motor catalytic cores, some move to the plus end of microtubules whereas others travel in the opposite direction. Crystal structures of the catalytic cores of conventional kinesin (a plus-end-directed motor involved in organelle transport) and ncd (a minus-end-directed motor involved in chromosome segregation) are nearly identical; therefore, the structural basis for their opposite directions of movement is unknown. Here we show that the ncd 'neck' made up of 13 class-specific residues next to the superfamily-conserved catalytic core, is essential for minus-end-directed motility, as mutagenesis of these neck residues reverses the direction of ncd motion. By solving the 2.5 A structure of a functional ncd dimer, we show that the ncd neck (a coiled-coil) differs from the corresponding region in the kinesin neck (an interrupted beta-strand), although both necks interact with similar elements in the catalytic cores. The distinct neck architectures also confer different symmetries to the ncd and kinesin dimers and position these motors with appropriate directional bias on the microtubule.     

Cardiovascular events and mortality in newly and chronically depressed persons > 70 years of age

The role of duration of depressed mood in the prediction of cardiovascular disease (CVD) requires further study, as it has been suggested that emerging depressive symptoms may be a better predictor than persistent depressive symptoms. This prospective cohort study of 3,701 men and women aged > 70 years uses 3 measurement occasions of depressive symptomatology (Center for Epidemiologic Studies-Depression Scale) during a 6-year period to distinguish persons who were newly (depressed at baseline but not at 3 and 6 years before baseline) and chronically depressed (depressed at baseline and at 3 or 6 years before baseline). Their risk of subsequent CVD events and all-cause mortality was compared with that of subjects who were never depressed during the 6-year period. Outcome events were based on death certificates and Medicare hospitalization records. During a median follow-up of 4.0 years, there were 732 deaths (46.2/1,000 person-years) and 933 new CVD events (64.7/1,000 person-years). In men, but not in women, newly depressed mood was associated with an increased risk of CVD mortality (relative risk 1.75, 95% confidence interval [CI] 1.00 to 3.05), new CVD events (relative risk 2.07, 95% CI 1.44 to 2.96), and new coronary heart disease events (relative risk 2.03, 95% CI 1.28 to 3.24) after adjustment for traditional CVD risk factors. The association between newly depressed mood and all-cause mortality was smaller (relative risk 1.40, 95% CI 0.95 to 2.07). Chronic depressed mood was not associated with new CVD events or all-cause mortality. Our findings suggest that newly depressed older men, but not women, were approximately twice as likely to have a CVD event than those who were never depressed. In men, recent onset of depressed mood is a better predictor of CVD than long-term depressed mood.     

A review of Lewy body disease, an emerging concept of cortical dementia

Small-diameter vascular grafts rapidly fail after implantation, due to occlusion caused by thrombosis. This problem cannot be overcome using medication. A promising improvement of graft patency is the seeding of endothelial cells (EC) on the luminal surface of the vascular graft. Conjugates of albumin and heparin, which were developed to obtain nonthrombogenic coatings, could form an ideal coating for vascular grafts. Besides presenting anticoagulant function, heparin will bind proteins with cell adhesive properties, thus facilitating adherence of EC to the graft surface. EC were able to grow to confluency on CO(2) gas plasma-treated polystyrene (PS-CO(2)) coated with albumin-heparin conjugate. CO(2) gas plasma treatment resulted in the introduction of functional groups at the surface (e.g., hydroxyl, aldehyde, carboxylic acid, and epoxide groups). Addition of albumin-heparin conjugate to the functionalized surface in an aqueous solution with pH 8.2 yielded a stable monolayer of covalently bound conjugate. The number of cells adhering and proliferating on this surface was comparable to the number of cells on fibronectin-coated PS-CO(2). However, the structure and size of EC proliferating on surface-immobilized albumin-heparin was more irregular. Long-term adherence might be improved by adding fibronectin to the albumin-heparin surface, either as a mixture with albumin-heparin or in a separate incubation step.     

Analyzing the evidence on European health care reforms

Health system reform, in Europe as elsewhere, has often been influenced as much by theory and conjecture as by fact and experience. In a study published in September 1997, the Regional Office for Europe of the World Health Organization (WHO) drew together the available evidence about the health care systems in the fifty-one countries of the European region. This paper focuses on western European countries. It reviews a variety of policy strategies and then explores implications from this European experience for the formulation of U.S. health care policy.     

Total mesenteric excision in the surgical treatment of rectal cancer: a prospective study

BACKGROUND: Total mesorectal excision has been advocated in conjunction with low anterior or abdominoperineal resection as the optimal surgical treatment for rectal cancer. It involves removal of the entire rectal mesentery as an intact unit and maximizes the likelihood of obtaining a negative circumferential margin. OBJECTIVES: To prospectively validate the efficacy of total mesorectal excision in obtaining locoregional control, to identify the perioperative factors influencing the selection of either a sphincter sparing or a sphincter ablating procedure, and to identify independent factors that may influence long-term prognosis in rectal cancers. SETTINGS: Tertiary referral center. PATIENTS: Seventy-three consecutive patients with rectal cancer located within 10 cm of the anal verge were treated from 1984 to 1997 by the senior author (F.M.). Sixty-five patients form the basis of our analysis after the exclusion of 7 patients who had their cancer removed transanally and 1 patient who had a permanent diverting stoma as the only procedure. RESULTS: Twenty-six patients underwent a sphincter ablating procedure; 39 underwent a sphincter sparing procedure. Operative mortality was 1.5%. Follow-up was complete in 64 patients (39+/-30 months; range, 3-126 months). Five-year actuarial survival rates were 88% for the 34 patients with stage I and II adenocarcinoma and 65% for the 22 patients with stage III adenocarcinoma. The local recurrence rate was 6.2% overall, but only 3.1% in the potentially curable group (stages I-III). When only patients who did not receive adjuvant chemoradiation therapy were considered (n=23), local recurrence rate was 8.3% overall and 0% in the potentially curable group. Tumor stage (P=.04) and vascular and/or lymphatic invasion (P=.002) were statistically significant in their association with survival. Circumferential lesions (P<.001), gross invasion of contiguous organs (P<.001) and distance from the anal verge of less than 5 cm (P=.01) were statistically significant in their association with the choice of a sphincter ablating procedure. CONCLUSIONS: This study confirms the efficacy of total mesorectal excision in minimizing locoregional recurrence rates and confirms the well-established prognostic value of stage and microinvasion. Moreover, it indicates that circumferential lesions, distance from anal verge, and gross invasion of contiguous organs are significant perioperative factors in the selection of the type of surgical procedure.     

What role do patients wish to play in treatment decision making?

BACKGROUND: Although current ideology suggests patients should be active participants in decision making about their care, the literature suggests that patients wish to be informed but not involved. OBJECTIVE: To test the hypothesis that most patients want their physicians to take the responsibility for problem solving (PS, identifying the one right answer), but that many want to be involved in decision-making (DM, selecting the most desired bundle of outcomes) tasks. METHODS: Survey responses from 300 patients undergoing angiogram at a Toronto, Ontario, hospital were analyzed (response rate, 72%). Survey items included scales to measure desire for information and participation, including Autonomy Preference Index, the Krantz Health Opinion Survey, and the Deber-Kraetschmer Problem-Solving Decision-Making Scale measured on a scale from, 1 (doctor only) to 5 (patient only). RESULTS: Patients had a relatively high desire for information. On the Problem-Solving Decision-Making Scale, they overwhelmingly wished the PS tasks to be performed by or shared with the physician (98.4% of the 12 PS scores are between 1 and 3), but wanted to be involved in DM (78% of the 6 DM scores are between 3 and 5). Preference for handing over control to the physician was significantly greater for the vignette involving potential mortality (chest pain) than for the vignettes involving mainly morbidity (urinary problems) or quality of life (fertility). CONCLUSIONS: Although patients do not wish to be involved in PS tasks, few wish to hand over DM control to their physician. These findings suggest 2 major roles for clinicians--assisting patients in PS to structure choices and supporting them in making often difficult decisions.     

Incisal edge reattachment: literature review and treatment perspectives

Anterior crown fractures in children and adolescents are a common form of injury, affecting approximately 25% of that population. Common restorative treatments such as composite bonding, laminate veneers, or full-coverage restorations tend to sacrifice healthy tooth structure and challenge dentists to match the adjacent unrestored dentition. Incisal edge fragment reattachment, including the use of current bonding techniques, is a restorative treatment option that offers the advantages of simplicity, immediate esthetics, and conservatism in cases of dental trauma. This article presents a comprehensive literature review on this restorative technique. It also provides diagnostic and treatment algorithms to simplify and clarify the recommended diagnostic and clinical regimens.