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Background and Purpose: The aim of this study was to assess the repeatability of neurite orientation dispersion and density imaging in healthy controls (HCs) and traumatic brain injury (TBI). Methods: Seventeen HCs and 48 TBI patients were scanned twice over 18 weeks with diffusion imaging. Orientation dispersion (ODI), neurite density (NDI), and the fraction of isotropic diffusion (F‐ISO) were quantified in regions of interest (ROIs) from a gray matter, subcortical, and white matter atlas and compared using the coefficient of variation for repeated measures (CVrep), which quantifies the expected percent change on repeated measurement. We used a modified signed likelihood ratio test (M‐SLRT) to compare the CVrep between groups in each ROI while correcting for multiple comparisons. Results: NDI exhibited excellent repeatability in both groups; the only group difference was found in the fusiform gyrus, where HCs exhibited better repeatability (M‐SLRT = 9.463, p =.0021). ODI also had excellent repeatability in both groups, although repeatability was significantly better in HCs in 16 cortical ROIs (p <.0022) and in the bilateral white matter and bilateral cortex (p <.0027). F‐ISO exhibited relatively poor repeatability in both groups, with few group differences. Conclusion: Overall, the repeatability of the NDI, ODI, and F‐ISO metrics over an 18‐week period is acceptable for assessing the effects of behavioral or pharmacological interventions, though caution is advised when assessing F‐ISO changes over time. [ABSTRACT FROM AUTHOR]

Obesity adversely impacts overall and cancer‐specific survival among breast cancer patients. Preclinical studies demonstrate negative energy balance inhibits cancer progression; however, feasibility and effects in patients are unknown. A two‐arm, single‐blinded, randomized controlled weight‐loss trial was undertaken presurgery among 32 overweight/obese, Stage 0–II breast cancer patients. The attention control arm (AC) received basic nutritional counseling and upper‐body progressive resistance training whereas the weight loss intervention (WLI) arm received identical guidance, plus counseling on caloric restriction and aerobic exercise to promote 0.68–0.92 kg/week weight loss. Anthropometrics, body composition, blood and survey data were collected at baseline and presurgery ∼30 days later. Tumor markers (e.g., Ki67) and gene expression were assessed on biopsy and surgical specimens; sera were analyzed for cytokines, growth and metabolic factors. Significant WLI vs. AC differences were seen in baseline‐to‐follow‐up changes in weight (−3.62 vs. −0.52 kg), %body fat (−1.3 vs. 0%), moderate‐to‐vigorous physical activity (+224 vs. +115 min/week), caloric density (−0.3 vs. 0 kcal/g), serum leptin (−12.3 vs. −4.0 ng/dl) and upregulation of tumor PI3Kinase signaling and cell cycle‐apoptosis related genes (CC‐ARG; all p‐values <0.05). Cytolytic CD56dimNK cell expression was positively associated with weight loss; CC‐ARG increased with physical activity. Increased tumor (nuclear) TNFα and IL‐1β, CX3CL1 and CXCL1 gene expression was observed in the WLI. Tumor Ki67 did not differ between arms. Feasibility benchmarks included 80% accrual, 100% retention, no adverse effects and excellent adherence. Short‐term weight loss interventions are feasible; however, mixed effects on tumor biology suggest unclear benefit to presurgical caloric restriction, but possible benefits of physical activity. What's new? Obesity adversely impacts survival among breast cancer patients. Preclinical studies demonstrate negative energy balance inhibits cancer progression; however, effects in patients are unknown. This is the first randomized controlled trial to assess the impact of a pre‐surgical weight loss intervention among early‐stage breast cancer patients. Results show the effects of acute negative energy balance on tumor biology, circulating biomarkers, and quality‐of‐life. Short‐term weight loss interventions are feasible; however, mixed effects on tumor biology suggest unclear benefit to pre‐surgical caloric restriction. Such interventions may be better timed after surgical resection, though cell cycle‐apoptosis and DNA damage‐repair scores support increasing physical activity. [ABSTRACT FROM AUTHOR]

Abstract: We compared the effects of an 8‐week iso‐caloric high‐protein (HP) diet versus a combined exercise regimen (Comb‐Ex) in individuals with long‐standing spinal cord injury (SCI). Effects on metabolic profiles, markers of inflammation, and signaling proteins associated with glucose transporter 4 (GLUT‐4) translocation in muscles were evaluated. Eleven participants with SCI completed the study (HP diet: n = 5; Comb‐Ex: n = 6; 46 ± 8 years; C5‐T12 levels; American Spinal Injury Association Impairment Scale A or B). The Comb‐Ex regimen included upper body resistance training (RT) and neuromuscular electrical stimulation‐induced‐RT for paralytic quadriceps muscles, interspersed with high‐intensity (80–90% VO2 peak) arm cranking exercises 3 days/week. The HP diet included ~30% total energy as protein (carbohydrate to protein ratio <1.5, ~30% energy from fat). Oral glucose tolerance tests and muscle biopsies of the vastus lateralis (VL) and deltoid muscles were performed before and after the trial. Fasting plasma glucose levels decreased in the Comb‐Ex (P < 0.05) group compared to the HP‐diet group. A decrease in areas under the curve for insulin and TNF‐α concentrations was observed for all participants regardless of group assignment (time effect, P < 0.05). Although both groups exhibited a quantitative increase in insulin sensitivity as measured by the Matsuda Index, the change was clinically meaningful only in the HP diet group (HP diet: pre, 4.6; post, 11.6 vs. Comb‐Ex: pre, 3.3; post, 4.6). No changes were observed in proteins associated with GLUT‐4 translocation in VL or deltoid muscles. Our results suggest that the HP‐diet and Comb‐Ex regimen may improve insulin sensitivity and decrease TNF‐α concentrations in individuals with SCI. [ABSTRACT FROM AUTHOR]

Thrombotic thrombocytopenic purpura (TTP) has >90% mortality without therapeutic plasma exchange (TPE). Despite TPE, approximately 10% of patients still die, presumably from cardiac ischemia. We sought clinical or laboratory parameters associated with death by reviewing the records of all patients hospitalized with acquired TTP in our institution for 10 years, and collect demographics and results for hemoglobin, platelet count, creatinine, lactate dehydrogenase, transaminases, total bilirubin, creatinine kinase (CK), CK-MB, and troponin I. Sixty-eight patients were admitted 88 times, and 11 died. Survivors and non-survivors were similar in terms of sex, ethnicity, thrombocytopenia, and degree of anemia at presentation, while the latter were older, had worse renal function and higher CK, CK-MB, and troponin I (univariate analysis). However, only troponin I remained significant on multivariate analyses. We propose that patients with TTP should be monitored with troponin I to detect significant myocardial ischemia that could predict death despite TPE. [ABSTRACT FROM AUTHOR]

ABSTRACT Objectives To measure microleakage around class V composite restorations after piezoelectric ultrasonic scaling and sonic toothbrushing. Methods 3 mm × 2 mm × 1.5 mm boxes were prepared on buccal and lingual surfaces of extracted molars centered on the cementum-enamel junction. Half the preparations were beveled (0.5 mm). Preparations were restored with composite and polished. Restorations on one side of the teeth were either traced with an ultrasonic scaler (60 seconds, n = 16) or brushed in a sonic toothbrushing machine (2 hours, n = 16). After thermocycling (10,000 cycles/5-55°C), specimens were immersed in 5 wt% Fuchsine solution (24 hours). Samples were sectioned and evaluated for percentage of dye penetration. Data were analyzed with an exact Wilcoxon rank-sum test and exact Wilcoxon signed-rank test (alpha = 0.05). Results Microleakage was observed at the cementum-composite interface but not the enamel-composite interface. There was not a statistically significant effect of the bevel for ultrasonic scaling or for sonic toothbrushing. Data obtained with and without a bevel were combined and a statistically significant difference in microleakage between the treatment and control sides of the tooth were found for ultrasonic scaling (32.5%±44.9%, n = 16; p = 0.016) but not sonic toothbrushing (2.5% ± 41.2%, n = 16; p = 1.0). Conclusions Piezoelectric ultrasonic scaling increased microleakage at cementum-composite interface and there was no difference in microleakage with the use of a bevel. Clinical Significance Piezoelectric sonic scaling around Class V composite restorations with margins in cementum should be avoided. Beveled margins will not reduce the incidence of microleakge resulting from ultrasonic scaling in Class V restorations. Placing the apical margin of the restoration in enamel should be attempted whenever possible to prevent future microleakage. (J Esthet Restor Dent 29:41-48, 2017) [ABSTRACT FROM AUTHOR]

BACKGROUND Current literature suggests that racial/ethnic minority survivors may be more likely than whites to experience economic hardship after a cancer diagnosis; however, little is known about such hardship. METHODS Patients with lung cancer (LC) and colorectal cancer (CRC) participating in the Cancer Care Outcomes Research and Surveillance (CanCORS) Consortium were surveyed approximately 4 months (baseline) and 12 months (follow-up) after diagnosis. Economic hardship at follow-up was present if participants 1) indicated difficulty living on household income; and/or 2) for the following 2 months, anticipated experiencing hardships (inadequate housing, food, or medical attention) or reducing living standards to the bare necessities of life. The authors tested whether African Americans (AAs) and Hispanics were more likely than whites to experience economic hardship controlling for sex, age, education, marital status, cancer stage, treatment, and economic status at baseline (income, prescription drug coverage). RESULTS Of 3432 survivors (39.7% with LC, 60.3% with CRC), 14% were AA, 7% were Hispanic, and 79% were white. AAs and Hispanics had lower education and income than whites. Approximately 68% of AAs, 58% of Hispanics, and 44.5% of whites reported economic hardship. In LC survivors, the Hispanic-white disparity was not significant in unadjusted or adjusted analyses, and the AA-white disparity was explained by baseline economic status. In CRC survivors, the Hispanic-white disparity was explained by baseline economic status, and the AA-white disparity was not explained by the variables that were included in the model. CONCLUSIONS Economic hardship was evident in almost 1 in 2 cancer survivors 1 year after diagnosis, especially AAs. Research should evaluate and address risk factors and their impact on survival and survivorship outcomes. Cancer 2015;121:1257-1264. © 2015 American Cancer Society. [ABSTRACT FROM AUTHOR]

Introduction Statistics is an essential training component for a career in clinical and translational science (CTS). Given the increasing complexity of statistics, learners may have difficulty selecting appropriate courses. Our question was: what depth of statistical knowledge do different CTS learners require? Methods For three types of CTS learners (principal investigator, co-investigator, informed reader of the literature), each with different backgrounds in research (no previous research experience, reader of the research literature, previous research experience), 18 experts in biostatistics, epidemiology, and research design proposed levels for 21 statistical competencies. Results Statistical competencies were categorized as fundamental, intermediate, or specialized. CTS learners who intend to become independent principal investigators require more specialized training, while those intending to become informed consumers of the medical literature require more fundamental education. For most competencies, less training was proposed for those with more research background. Discussion When selecting statistical coursework, the learner's research background and career goal should guide the decision. Some statistical competencies are considered to be more important than others. Baseline knowledge assessments may help learners identify appropriate coursework. Conclusion Rather than one size fits all, tailoring education to baseline knowledge, learner background, and future goals increases learning potential while minimizing classroom time. [ABSTRACT FROM AUTHOR]

Among postmenopausal women, declining estrogen may facilitate fat partitioning from the periphery to the intra-abdominal space. Furthermore, it has been suggested that excess androgens contribute to a central fat distribution pattern in women. The objective of this longitudinal study was to identify independent associations of the hormone milieu with fat distribution in postmenopausal women. Fifty-three healthy postmenopausal women, either using or not using hormone replacement therapy (HRT) were evaluated at baseline and 2 years. The main outcomes were intra-abdominal adipose tissue (IAAT), subcutaneous abdominal adipose tissue, and total thigh fat analyzed by computed tomography scanning and leg fat and total body fat mass measured by dual-energy X-ray absorptiometry. Serum estradiol, estrone, estrone sulfate, total testosterone, free testosterone, androstenedione, dehydroepiandrosterone sulfate), sex hormone-binding globulin (SHBG), and cortisol were assessed. On average, in all women combined, IAAT increased by 10% (10.5 cm2) over 2 years (P < 0.05). Among HRT users, estradiol was inversely associated with, and estrone was positively associated with, 2-year gain in IAAT. Among HRT nonusers, free testosterone was inversely associated with, and SHBG was positively associated with, 2-year gain in IAAT. These results suggest that in postmenopausal women using HRT, greater circulating estradiol may play an integral role in limiting lipid deposition to the intra-abdominal cavity, a depot associated with metabolically detrimental attributes. However, a high proportion of weak estrogens may promote fat partitioning to the intra-abdominal cavity over time. Furthermore, among postmenopausal women not using HRT, greater circulating free testosterone may limit IAAT accrual. [ABSTRACT FROM AUTHOR]

Changes in markers of inflammation (MOI) and fat distribution with weight loss between African-American (AA) and white (W) women have yet to be characterized. The purpose of this study was to examine potential ethnic differences in MOI and regional fat distribution with weight loss, and identify the associations between these markers and changes in regional fat distribution with weight loss among AA and W women. Subjects were 126 healthy, premenopausal women, BMI 27-30 kg/m2. They were placed on a weight-loss intervention consisting of diet and/or exercise until a BMI <25 was achieved. Fat distribution was measured with computed tomography, and body composition with dual-energy X-ray absorptiometry. Serum concentrations of tumor necrosis factor-α (TNF-α), soluble TNF receptor-I (sTNFR-I), sTNFR-II, C-reactive protein (CRP), and interleukin-6 (IL-6) were assessed. All MOI and adiposity measures significantly decreased with weight loss. Significant ethnic differences with weight loss were observed for fat mass, body fat, intra-abdominal adipose tissue (IAAT), sTNFR-I, and sTNFR-II. Mixed-model analysis indicated that adjusting for change in IAAT explained ethnic differences in change in TNF-α and the decrease in TNF-α with weight loss, while total fat mass only explained the decrease in sTNFR-I and sTNFR-II with weight loss. In conclusion, all MOI decreased following weight loss among W, whereas only IL-6 and CRP decreased following weight loss in AA. The most distinct phenotypic difference observed was a greater impact of weight loss on TNF-α in W compared to AA, which was directly associated with IAAT in W. [ABSTRACT FROM AUTHOR]

Increasing demands for evidence-based medicine and for the translation of biomedical research into individual and public health benefit have been accompanied by the proliferation of special units that offer expertise in biostatistics, epidemiology, and research design (BERD) within academic health centers. Objective metrics that can be used to evaluate, track, and improve the performance of these BERD units are critical to their successful establishment and sustainable future. To develop a set of reliable but versatile metrics that can be adapted easily to different environments and evolving needs, we consulted with members of BERD units from the consortium of academic health centers funded by the Clinical and Translational Science Award Program of the National Institutes of Health. Through a systematic process of consensus building and document drafting, we formulated metrics that covered the three identified domains of BERD practices: the development and maintenance of collaborations with clinical and translational science investigators, the application of BERD-related methods to clinical and translational research, and the discovery of novel BERD-related methodologies. In this article, we describe the set of metrics and advocate their use for evaluating BERD practices. The routine application, comparison of findings across diverse BERD units, and ongoing refinement of the metrics will identify trends, facilitate meaningful changes, and ultimately enhance the contribution of BERD activities to biomedical research. Copyright © 2011 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

BACKGROUND: [ABSTRACT FROM AUTHOR]

The independent effects of exercise and weight loss on markers of inflammation (MOI) in obese individuals have not been clearly characterized. The objectives of this study were to: (i) identify the independent effects of exercise and weight loss on MOI and (ii) determine whether changes in MOI were associated with changes in fat distribution. Subjects were 126 healthy, premenopausal women, BMI 27-30 kg/m2. They were randomized to one of three groups: diet only, diet + aerobic-, or diet + resistance training until a BMI <25 kg/m2 was achieved. Fat distribution was measured with computed tomography, and body composition with dual-energy X-ray absorptiometry. Serum concentrations of tumor necrosis factor (TNF)-α, soluble TNF receptor 1 (sTNF-R1), soluble TNF receptor 2 (sTNF-R2), C-reactive protein (CRP), and interleukin (IL)-6 were assessed. Results of repeated-measures ANOVA indicated a significant effect of time on MOI, such that MOI decreased with weight loss. Results of mixed-model analysis indicated that adjusting for intra-abdominal adipose tissue (IAAT) and total fat mass explained the decreases in TNF-α and sTNF-R1, whereas only total fat mass explained the decreases in sTNF-R2, IL-6, and CRP. In conclusion, weight loss was associated with decreases in MOI. The effect of weight loss appeared to be mediated by changes in total fat mass or IAAT. Addition of exercise did not alter the response, suggesting that weight loss has a more profound impact for reducing MOI in overweight women than exercise. [ABSTRACT FROM AUTHOR]

The prevalence of type 2 diabetes is greater among African Americans (AA) vs. European Americans (EA), independent of obesity and lifestyle. We tested the hypothesis that intramyocellular lipid (IMCL) or extramycellular lipid (EMCL) would be associated with insulin sensitivity among healthy young women, and that the associations would differ with ethnic background. We also explored the hypothesis that adipokines and estradiol would be associated with muscle lipid content. Participants were 57 healthy, normoglycemic, women and girls mean age 26 (±10) years; mean BMI 27.3 (±4.8) kg/m²; 32 AA, 25 EA. Soleus IMCL and EMCL were assessed with ¹H magnetic resonance spectroscopy (MRS); insulin sensitivity with an insulin-modified frequently sampled intravenous glucose tolerance test and minimal modeling; body composition with dual-energy X-ray absorptiometry; and intra-abdominal adipose tissue (IAAT) with computed tomography. Adiponectin, leptin, and estradiol were assessed in fasting sera. Analyses indicated that EMCL, but not IMCL, was greater in AA vs. EA (2.55 ± 0.16 vs. 1.98 ± 0.18 arbitrary units, respectively, P < 0.05; adjusted for total body fat). IMCL was associated with insulin sensitivity in EA (r = -0.54, P < 0.05, adjusted for total fat, IAAT, and age), but not AA (r = 0.16, P = 0.424). IMCL was inversely associated with adiponectin (r = -0.31, P < 0.05, adjusted for ethnicity, age, total fat, and IAAT). In conclusion, IMCL was a significant determinant of insulin sensitivity among healthy, young, EA but not AA women. Further research is needed to determine whether the component lipids of IMCL (e.g., diacylglycerol (DAG) or ceramide) are associated with insulin sensitivity in an ethnicity specific manner. [ABSTRACT FROM AUTHOR]

Calcium intake is reported to enhance weight loss with a preferential loss in trunk fat. Discrepant findings exist as to the effects of calcium intake on longitudinal changes in total fat mass and central fat deposition. Therefore, the purpose of this study was to determine associations between dietary calcium intake and 1-year change in body composition and fat distribution, specifically intra-abdominal adipose tissue (IAAT). A total of 119 healthy, premenopausal women were evaluated at baseline and 1 year later. Average dietary calcium was determined via 4-day food records. Total fat was determined by dual-energy X-ray absorptiometry (DXA) and subcutaneous abdominal adipose tissue (SAAT) and IAAT by computed tomography. Over the study period, participants' reported daily calcium and energy intakes were 610.0 ± 229.9 mg and 1,623.1 ± 348.5 kcal, respectively. The mean change in weight, total fat, IAAT, and SAAT was 4.9 ± 4.4 kg, 5.3 ± 4.0 kg, 7.7 ± 19.5 cm2, and 49.3 ± 81.1 cm2, respectively. Average calcium intake was significantly, inversely associated with 1-year change in IAAT (standardized β: −0.23, P < 0.05) after adjusting for confounding variables. For every 100 mg/day of calcium consumed, gain in IAAT was reduced by 2.7 cm2. No significant associations were observed for average calcium intake with change in weight, total fat, or SAAT. In conclusion, dietary calcium intake was significantly associated with less gain in IAAT over 1 year in premenopausal women. Further investigation is needed to verify these findings and determine the calcium intake needed to exert beneficial effects on fat distribution. [ABSTRACT FROM AUTHOR]

Ethnic differences in insulin secretion and action between African Americans (AAs) and European Americans (EAs) may influence mobilization of free fatty acids (FFAs). We tested the hypotheses that FFA concentrations would be associated with measures of insulin secretion and action before and during a glucose challenge test. Subjects were 48 prepubertal girls, 60 premenopausal women, and 46 postmenopausal women. Fasting insulin (insulin0), the acute insulin response to glucose (AIRg), the insulin sensitivity index (SI), basal and nadir FFA (FFA0, FFAnadir), and nadir time (TIMEnadir) were determined during an intravenous glucose tolerance test (IVGTT). Stepwise multiple linear regression (MLR) analysis was conducted to identify associations of FFA0, FFAnadir, and TIMEnadir with ethnicity, age group, insulin measures, indexes of body composition from dual-energy X-ray absorptiometry, and measures of fat distribution from computed tomography scan. In this population, insulin0 and AIRg were higher among AAs vs. EAs, whereas SI was lower, independent of age group. MLR analyses indicated that FFA0 was best predicted by lean tissue mass (LTM), leg fat mass, ethnicity (lower in AAs), SI, and insulin0. FFAnadir was best predicted by FFA0, age group, and intra-abdominal adipose tissue (IAAT). TIMEnadir was best predicted by leg fat mass, AIRg, and SI. In conclusion, indexes of insulin secretion and action were associated with FFA dynamics in healthy girls and women. Lower FFA0 among AAs was independent of insulin0 and SI. Whether lower FFA0 is associated with substrate oxidation or risk for obesity remains to be determined. [ABSTRACT FROM AUTHOR]

Medical students, residents, postdoctoral fellows, and faculty commonly consult with biostatistical experts about study design and data analysis when conducting clinical research. The role of biostatistical training during these consultations is examined, and characterizations of the connections between biostatistical consultation and education are reviewed. The presence and kinds of teaching efforts during biostatistical consults at four academic research institutions over various periods of time between 1999 and 2005 (237 consultations in total) were recorded and are described. By site, 67, 70, 78, and 100 per cent of the consulting sessions included biostatistical training, with an overall 78 per cent (95 per cent CI: 73-83 per cent) of consultations including an educational component when all consultations were combined. Training covered a wide range of biostatistical topics. Seventy-five per cent of the consultations with faculty (120/161), 79 per cent with fellows and residents (31/39), and 100 per cent with medical students (10/10) included some degree of instruction in study design or statistical analysis topics. Results show that both the need and the opportunity exist for specialized biostatistical instruction during one-on-one sessions between a consulting biostatistician and physicians, medical students, and research staff. Academic researchers are ideally positioned to absorb this kind of training when they initiate a request for assistance with their own research project. Copyright © 2006 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

BACKGROUND: Thrombotic thrombocytopenic purpura-hemolytic uremic syndrome (TTP-HUS) is a diagnosis of exclusion when a patient presents with the sine qua non findings of thrombocytopenia and microangiopathic hemolytic anemia without an identifiable cause. Although most patients respond to therapeutic plasma exchange (TPE), a significant number of patients relapse. The aim was to determine if clinical, laboratory, and/or treatment features could predict response and/or relapse. STUDY DESIGN AND METHODS: This study was a retrospective review of adults with TTP-HUS treated with TPE at our institution from January 1996 to February 2004. RESULTS: The study population consisted of 90 patients (69% female) with mean age of 45 years and mostly obese (65%). The majority of cases were considered idiopathic. Ten patients died (11%) from the disease before achieving a response, whereas 79 percent were considered responders. Obesity and severe anemia at presentation were predictors of response to TPE (p = 0.0126 and p = 0.0071, respectively). Among the responders, 28 percent relapsed in a median of 14 months. Male sex, severe thrombocytopenia (mean ± SD, 13 × 109 ± 8 × 109/L), and higher lactate dehydrogenase pre-/posttreatment ratio were associated with relapse (p values of 0.0141, 0.0199, and 0.0407, respectively). ADAMTS-13 values were not obtained on enough number of patients to provide important data. CONCLUSION: Although patient and laboratory characteristics associated with response and relapse were identified, there was significant overlap between patient groups. Thus, our findings offer preliminary evidence and do not yet justify short- or long-term changes in the management of patients with TTP-HUS. [ABSTRACT FROM AUTHOR]

The purpose of this study is to examine the relationship of a rural clerkship to medical students' interest in establishing careers in rural communities. The Association of American Medical Colleges Medical School Graduation Questionnaire (GQ) for years 1988 through 1997 was examined to compare the career plans of students graduating from Morehouse School of Medicine (MSM) with those of all students graduating from United States medical schools before the period 1988 through 1992 and after the period 1993 through 1997, after the inception of the rural clerkship at MSM. Select GQ data items examined include student demographics, medical school experiences, and career plans. Statistical analyses were used to compare pre- and post-clerkship responses for MSM students and to compare their responses with the national trends. Results indicate that, following a transition period, MSM students showed an increased preference for a future career in a rural community. A smaller upward trend in the national data was observed. There appears to be an association between the rural clerkship experience at MSM and the stated preferred career choices of the students. [ABSTRACT FROM AUTHOR]

Objective: To determine if folinic acid supplementation during methotrexate (MTX) therapy for rheumatoid arthritis (RA) reduces both urinary 5-aminoimidazole-4-carboxamide (AICA) and urinary adenosine excretion more than does folic acid supplementation. AICA and adenosine are markers for MTX interference with purine metabolism., Methods: Forty patients with RA who received MTX for 6 weeks were randomized to receive either daily folic acid or folinic acid supplements during an additional week of MTX therapy. Colorimetric and radioimmunocompetition assays were used to measure 24-hour urinary AICA and adenosine excretion levels, respectively., Results: At the end of 6 weeks, 24-hour urinary levels of AICA, but not adenosine, were elevated as compared with baseline levels (i.e., prior to MTX therapy). Folinic acid, but not folic acid, supplementation normalized urinary AICA levels during MTX therapy. Relatively high urinary levels of AICA were correlated with reduced disease activity. No similar correlations were seen with urinary adenosine levels., Conclusion: The blockade of purine nucleotide biosynthesis by MTX at the AICA ribonucleotide transformylase-catalyzed step may be related to the efficacy of MTX, and this blockade is effectively relieved by folinic acid, but not by folic acid, supplementation., (Copyright 2004 American College of Rheumatology)