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Translation as a Function of Modality
Werch, Chudley E., Grenard, Jerry L., Burnett, Jeanpaul, Watkins, Julia A., Ames, Steve, Jobli, Edessa

Evaluation & the Health Professions | March 1, 2006 | Volume: 29 | Issue: 1 | Pages: 89-125

10.1177/0163278705284444 | PMID 16510881 Get It

The purpose of this article is to examine the potential of brief intervention (BI) as a modality for translating health behavior intervention research into practice. We discuss common definitions of BI, applications within common models of translation research, effects of BI on a range of health behaviors and across various populations, current and potential mechanisms, and uses for dissemination to practice. A number of advantages of BI suggest they are well suited for translating behavioral research. In addition, findings from 13 systematic reviews of BI effects show their potential versatility. Basic research on motivation, decision making, and persuasion may be applied to the design of BIs (Type 1 translation). Suggestions for translating BI research into practice are discussed (Type 2 translation). The article concludes that efforts to use BIs to translate research into practice are currently underdeveloped. Recommendations are provided for using BI in translating research into practice.
An Interpositional Elastomeric Cap for Metacarpophalangeal Joint Perichondrioplasty in Rheumatoid Arthritis
Jackson, Ian T., Sully, L., Tanner, N.S.B., McGlynn, Michael

Hand | March 1, 2006 | Volume: os-13 | Issue: 2 | Pages: 158-163

10.1016/s0072-968x(81)80056-3 | PMID 7286800 Get It

A new interpositional elastomeric cap was developed and used for perichondrioplasty in six rheumatoid metacarpophalangeal joints. Adequate cartilage formation occurred, and the joint contours were more normal than those achieved by previous methods.
Cofactor-containing antibodies: Crystal structure of the original yellow antibody
Wentworth, Paul, Kyle, Robert A. , Lerner, Richard A. , Wilson, Ian A. , Zhu, Xueyong

Proceedings of the National Academy of Sciences | February 28, 2006 | Volume: 103 | Issue: 10 | Pages: 3581-3585

10.1073/pnas.0600251103 | PMID 16537445 Get It

Antibodies are generally thought to be a class of proteins that function without the use of cofactors. However, it is not widely appreciated that antibodies are believed to be the major carrier protein in human circulation for the important riboflavin cofactor that is involved in a host of biological phenomena. A further link between riboflavin and antibodies was discovered 30 years ago when a bright-yellow antibody, IgG GAR , was purified from a patient with multiple myeloma who had turned yellow during the course of her disease. It was subsequently shown that the yellow color of this antibody was due to riboflavin binding. However, it was not known how and where riboflavin was bound to this antibody. We now report the crystal structure of this historically important IgG GAR Fab at 3.0-Å resolution. The riboflavin is located in the antigen-combining site with its isoalloxazine ring stacked between the parallel aromatic moieties of TyrH33, PheH58, and TyrH100A. Together with additional hydrogen bonds, these interactions reveal the structural basis for high-affinity riboflavin binding. The ligand specificity of IgG GAR is compared with another riboflavin-binding antibody, IgG DOT , which was purified from a second patient with multiple myeloma. The crystal structure of IgG GAR provides a starting point for attempts to understand the physiological relevance and chemical functions of cofactor-containing antibodies.
Chromatin Assembly Factor 1 Interacts with Histone H3 Methylated at Lysine 79 in the Processes of Epigenetic Silencing and DNA Repair
Zhou, Hui , Muddiman, David C. , Madden, Benjamin J. , Zhang, Zhiguo

Biochemistry | February 28, 2006 | Volume: 45 | Issue: 9 | Pages: 2852-2861

10.1021/bi0521083 | PMID 16503640 Get It

Fulvestrant in Women With Advanced Breast Cancer After Progression on Prior Aromatase Inhibitor Therapy: North Central Cancer Treatment Group Trial N0032
Rowland, Kendrith M. , Mirchandani, D., Bernath, Albert M., Camoriano, John , Fishkin, Paul A. S., Nikcevich, Daniel A., Perez, Edith A. , Ingle, James N. , Suman, Vera J.

Journal of Clinical Oncology | February 28, 2006 | Volume: 24 | Issue: 7 | Pages: 1052-1056

10.1200/jco.2005.04.1053 | PMID 16505423 Get It

PurposeFulvestrant is an antiestrogen that leads to estrogen receptor degradation and has demonstrated efficacy in breast cancer patients who have had disease recurrence or progression after tamoxifen. This study was designed to examine the efficacy and toxicity of fulvestrant in patients with disease progression on a third-generation aromatase inhibitor (AI).Patients and MethodsA one-stage phase II trial was conducted in postmenopausal women with measurable disease by Response Evaluation Criteria in Solid Tumors criteria who experienced disease progression after treatment with a third-generation AI and, at most, one additional hormonal agent. Tumors must have been estrogen receptor and/or progesterone receptor positive. The primary end point was objective response rate, and secondary end points were time to disease progression, survival, duration of response, and toxicity.ResultsEighty patients were enrolled, and three were ineligible. Characteristics of the 77 eligible patients included median age of 68 years, performance score of 0 or 1 in 91% of patients, visceral dominant disease in 88% of patients, two prior hormonal treatments in 73% of patients, and prior chemotherapy for metastatic disease in 32% of patients. Eleven patients (14.3%) achieved a partial response, and 16 patients (20.8%) had stable disease for at least 6 months, for a clinical benefit rate of 35%. Antitumor activity seemed to be higher in women with prior treatment with AI alone compared with women whose prior treatment also included tamoxifen. Median time to progression was 3 months, and median survival time was 20.2 months. Fulvestrant was well tolerated.ConclusionFulvestrant is a well-tolerated treatment and has efficacy against breast cancers that have progressed after therapy with a third-generation AI.
Phase III Study of Two Different Dosing Schedules of Erythropoietin in Anemic Patients With Cancer
Steensma, David P. , Molina, R, Sloan, Jeff A. , Nikcevich, Daniel A., Schaefer, Paul, Rowland, Kendrith M. , Dentchev, Todor, Novotny, Paul J. , Tschetter, Loren K., Hogan, Thomas F., Law, Amy , Loprinzi, Charles L. , Alberts, Steven R. , Steensma, David P

Journal of Clinical Oncology | February 28, 2006 | Volume: 24 | Issue: 7 | Pages: 1079-1089

10.1200/jco.2005.02.7276 | PMID 16505427 Get It

Purpose To compare maintenance epoetin alfa administered once every 3 weeks with continued weekly epoetin alfa for patients with cancer-associated anemia. Patients and Methods Eligible patients were randomly assigned at enrollment to receive three weekly doses of epoetin alfa 40,000 U subcutaneously (SC), followed by either standard weekly epoetin alfa (40K arm) or 120,000 U of epoetin alfa (120K arm) SC every 3 weeks for 18 additional weeks. Results Three hundred sixty-five patients were enrolled. One hundred eighty-three patients were assigned to the 40K arm, and 182 were assigned to the 120K arm. There was no difference in the proportion of patients requiring transfusions during the study (23% in 40K arm and 18% in 120K arm, P = .22) or specifically during the maintenance phase (13% in 40K arm v 15% in 120K arm, P = .58). Patients randomly assigned to the 40K arm were more likely to have a ≥ 2 or ≥ 3 g/dL hemoglobin (Hb) increment, were more likely to have a drug dose held because of high Hb, and had higher mean end-of-study Hb levels. Toxicities, including thromboembolism, and overall survival were similar. Patients in the 40K arm had a higher global quality of life (QOL) at baseline for unclear reasons, whereas patients in the 120K arm had a greater global QOL improvement during the study, so end-of-study QOL was equivalent. Conclusion After three weekly doses of epoetin alfa 40,000 U, a dose of 120,000 U can be administered safely once every 3 weeks without increasing transfusion needs or sacrificing QOL. The Hb increment is somewhat greater with continued weekly epoetin alfa. Lack of blinding as a result of different treatment schedules may have confounded results.
Effects of a γ-secretase inhibitor in a randomized study of patients with Alzheimer disease
Siemers, Eric , Quinn, Joseph F. , Kaye, Jeffrey , Farlow, Martin R. , Porsteinsson, Anton P. , Tariot, Pierre N. , Zoulnouni, P., Knopman, David S., Satterwhite, Julie, Gonzales, Celedon, May, Patrick C. , Galvin, James E. , Holtzman, David M. , Dean, Ralph A. , Quinn, Joseph F

Neurology | February 27, 2006 | Volume: 66 | Issue: 4 | Pages: 602-604

10.1212/01.wnl.0000198762.41312.e1 | PMID 16505324 Get It

Recycling of ESCRTs by the AAA-ATPase Vps4 is regulated by a conserved VSL region in Vta1
Azmi, Ishara F. , Davies, Brian A., Dimaano, Christian , Payne, Johanna A., Eckert, Debra M., Babst, Markus , Katzmann, David J.

The Journal of Cell Biology | February 27, 2006 | Volume: 172 | Issue: 5 | Pages: 705-717

10.1083/jcb.200508166 | PMID 16505166 Get It

In eukaryotes, the multivesicular body (MVB) sorting pathway plays an essential role in regulating cell surface protein composition, thereby impacting numerous cellular functions. Vps4, an ATPase associated with a variety of cellular activities, is required late in the MVB sorting reaction to dissociate the endosomal sorting complex required for transport (ESCRT), a requisite for proper function of this pathway. However, regulation of Vps4 function is not understood. We characterize Vta1 as a positive regulator of Vps4 both in vivo and in vitro. Vta1 promotes proper assembly of Vps4 and stimulates its ATPase activity through the conserved Vta1/SBP1/LIP5 region present in Vta1 homologues across evolution, including human SBP1 and Arabidopsis thaliana LIP5. These results suggest an evolutionarily conserved mechanism through which the disassembly of the ESCRT proteins, and thereby MVB sorting, is regulated by the Vta1/SBP1/LIP5 proteins.
Phase III Comparison of Depomedroxyprogesterone Acetate to Venlafaxine for Managing Hot Flashes: North Central Cancer Treatment Group Trial N99C7
Loprinzi, Charles L. , Levitt, Ralph, Barton, Debra L. , Sloan, Jeff A. , Dakhil, Shaker R. , Nikcevich, Daniel A., Bearden, James D. , Mailliard, James A., Tschetter, Loren K., Fitch, Tom R., Kugler, John W.

Journal of Clinical Oncology | February 27, 2006 | Volume: 24 | Issue: 9 | Pages: 1409-1414

10.1200/jco.2005.04.7324 | PMID 16505409 Get It

Purpose Vasomotor hot flashes are a common problem in menopausal women. Given concerns regarding estrogen and/or combined hormonal therapy, other treatment options are desired. Prior trials have confirmed that progestational agents and newer antidepressants effectively reduce hot flashes. This current trial compared a single intramuscular dose of medroxyprogesterone acetate (MPA), depot preparation, versus daily oral venlafaxine as treatment for hot flashes. Methods Women with bothersome hot flashes were entered onto this trial, were randomly assigned to treatment, and then had a baseline week where hot flash scores were recorded without treatment. They were then treated and observed for 6 weeks; daily diaries were used to measure hot flash frequencies and severities. There were 109 patients per each arm randomly assigned to receive MPA 400 mg intramuscularly for a single dose versus venlafaxine 37.5 mg per day for a week, then 75 mg per day. Results During the sixth week after random assignment, hot flash scores were reduced by 55% in the venlafaxine arm versus 79% in the MPA arm (P < .0001). In an intention-to-treat analysis, 46% of venlafaxine patients (50 of 109) compared with 74% of the MPA patients (81 of 109) had a decrease in hot flashes by more than 50% from baseline (P < .0001). Less toxicity was reported in the MPA arm. Conclusion A single MPA dose seems to be well tolerated and more effectively reduces hot flashes than does venlafaxine.
The NIH Cognitive and Emotional Health Project
Hendrie, Hugh C. , Albert, Marilyn , Butters, Meryl A. , Gao, Sujuan , Yaffe, Kristine , Cuthbert, Bruce N. , Edwards, Emmeline , Wagster, Molly V., Knopman, David S. , Launer, Lenore J.

Alzheimer's & Dementia | February 24, 2006 | Volume: 2 | Issue: 1 | Pages: 12-32

10.1016/j.jalz.2005.11.004 | PMID 19595852 Get It

AbstractBackgroundThe Cognitive and Emotional Health Project (CEHP) seeks to identify the demographic, social, and biological determinants of cognitive and emotional health in the older adult. As part of the CEHP, a critical evaluation study committee was formed to assess the state of epidemiological research on demographic, social, and biological determinants of cognitive and emotional health.MethodsCriteria for inclusion in the survey were large cohort studies, longitudinal in design, participants predominantly 65 years or older, with measurements of both cognition and emotion, and information on a wide variety of demographic, psychosocial, and biological factors. North American and European studies, which met these criteria, were selected for the review. Outcome measures included cognition, cognitive decline, and cognitive function. For emotion, symptoms included depression and anxiety, positive and negative affect, subjective well being, mastery, and resilience.ResultsNinety‐six papers were identified that addressed cognitive and emotional outcomes. A large variety of risk factors were consistently identified with cognitive outcomes, particularly those previously associated with increased risk of cardiovascular disease. There was considerable overlap between risk factors for cognitive and emotional outcomes.ConclusionThis review identifies a large number of lifestyle and health behaviors that alter the risk for maintenance of cognitive and emotional health. Large longitudinal cohort studies are a unique source to explore factors associated with cognitive and emotional health. Secondary analyses of these studies should be encouraged as should the development of standardized questionnaires to measure cognitive and emotional health. Future research in this field should study cognitive and emotional health simultaneously.