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Background: Clinicians' accuracy in perceiving nonverbal cues has potentially important consequences, but has received insufficient research., Objective: To examine the relation of medical students' nonverbal sensitivity to their gender and personal traits, as well as to their communication and impressions made during a standardized patient (SP) visit., Design: Psychometric testing, questionnaire, and observation., Setting: One US medical school., Participants: Two-hundred seventy-five third-year medical students., Measurements: Nonverbal sensitivity and attitudes were measured using standard instruments. Communication during the SP visit was measured using trained coders and analogue patients who viewed the videotapes and rated the favorability of their impressions of the student., Results: Nonverbal sensitivity was higher in female than male students (P < 0.001) and was positively correlated with self-reported patient-centered attitudes (P < 0.01) and ability to name one's own emotions (P < 0.05). It was also associated with less distressed (P < 0.05), more dominant (P < 0.001), and more engaged (P < 0.01) behavior by the SP, and with more liking of the medical student (P < 0.05) and higher ratings of compassion (P < 0.05) by the analogue patients. Correlations between nonverbal sensitivity and other variables were generally stronger and different for male than female students, but nonverbal sensitivity predicted analogue patients' impressions similarly for male and female students., Conclusion: Medical students' nonverbal sensitivity was related to clinically relevant attitudes and behavioral style in a clinical simulation.

Purpose: Differences in prostate cancer incidence, grade and stage at diagnosis, and survival in black vs nonblack men are well documented. Recent studies indicate that lipids may have a role in oncogenesis, including that of prostate cancer. We investigated the relationship between circulating lipids in black and nonblack patients, and newly diagnosed prostate cancer., Materials and Methods: The study population included consecutive patients who underwent prostate biopsy for increased prostate specific antigen and/or abnormal digital rectal examination at Atlanta Veterans Affairs Medical Center. Age, race, prostate specific antigen, prostate volume, body mass index, family history, high and low density lipoprotein, triglyceride and cholesterol lowering medications were included in data analysis., Results: A total of 1,775 men with complete information were included in data analysis. A total of 521 black and 451 white men had positive biopsies. Using 100 mg/dl or less as the referent the adjusted OR reflecting the association of low density lipoprotein and prostate cancer diagnosis in black men was 1.49 (95% CI 1.04-2.13, p = 0.031), 1.51 (95% CI 0.96-2.39, p = 0.076) and 3.24 (95% CI 1.59-6.92, p = 0.002) for low density lipoprotein greater than 100 to 130, greater than 130 to 160 and greater than 160 mg/dl, respectively. Corresponding results in nonblack men showed no significant association., Conclusions: Increased serum low density lipoprotein is associated with an increased likelihood of prostate cancer diagnosis in black men but not in nonblack men. This association is strongest in the highest low density lipoprotein risk category. The reasons for the racial differences are unknown but may include genetic, dietary or other environmental factors.

Objective: To examine the safety and efficacy of emergency transradial primary percutaneous coronary intervention for ST-elevation myocardial infarction., Design: Single-centre observational study with prospective data collection., Setting: A regional cardiac centre, United Kingdom., Patients: 1051 consecutive patients admitted with ST-elevation myocardial infarction, without cardiogenic shock, between November 2004 and October 2008., Interventions: Percutaneous coronary interventions by radial and femoral access, Main Outcome Measures: The primary outcome measures were procedural success, major vascular complication and failed initial access strategy. Secondary outcomes were in-hospital mortality and major adverse cardiac and cerebrovascular events, needle-to-balloon times, contrast volume used, radiation dose absorbed and time to discharge. Multiple regression analysis was used to adjust for potential differences between the groups., Results: 571 patients underwent radial access and 480 femoral. A variable preference for radial access was observed among the lead operators (between 21% and 90%). Procedural success was similar between the radial and femoral groups, but major vascular complications were more frequent at the site of femoral access (0% radial versus 1.9% femoral, p = 0.001). Failure of the initial access strategy was more frequent in the radial group (7.7% versus 0.6%, p<0.001). Adjustment for other procedural and clinical predictors did not alter these findings. Needle-to-balloon time, as a measure of procedural efficiency, was equal for radial and femoral groups., Conclusions: In the setting of acute ST-elevation myocardial infarction without cardiogenic shock, transradial primary angioplasty is safe, with comparable outcomes to a femoral approach and a lower risk of vascular complications.

Objective: To examine the consequences of expressions of uncertainty (EOUs) in medical student interactions, with a particular focus on the gender of the expressor., Methods: EOUs were identified in 147 videotaped interactions between third-year medical students and standardized patients enacting four medical scenarios. The encounters were also analyzed using the Roter Interaction Analysis System (RIAS). A subset of these interactions was shown to 244 analogue patients who rated satisfaction, liking, and perceived competence and confidence., Results: Female medical students used more EOUs but not when adjusted for total number of statements. The EOU rate varied across scenarios. A higher EOU rate was perceived as more affectively negative by both RIAS trained coders and analogue patients. EOU rate was inversely related to analogue patient satisfaction and liking and this relationship was stronger for males than females. Female student use of EOUs was more strongly associated with ratings of anxiety than was male EOU use., Conclusion: There was an overall negative perception of medical students who expressed uncertainty; however, the strength of the associations varied due to medical student gender., Practice Implications: The implications for medical education are discussed.

A major issue in pain literature is whether an etiological association between pain, sleep, and vitality exists. We utilized data from clinical trials of duloxetine for management of diabetic peripheral neuropathic pain (DPNP) to investigate these associations. Data were pooled from 3 double-blind, randomized, placebo-controlled, 12-week trials of patients without mood disorder (N = 1,139). After excluding 442 patients who reported maximum vitality at baseline, experienced treatment-emergent somnolence, asthenia or fatigue, or were taking sedating concomitant medications or duloxetine 20 mg/day, 697 were included in the analysis. Efficacy measures included weekly mean scores for average daily and night pain, pain interference with sleep, and vitality. Baseline to end point mean improvements in daily and night pain, Brief Pain Inventory sleep interference, and vitality were significantly superior for duloxetine compared with placebo (P < or = 0.001). Correlations between changes in daily and night pain, and sleep interference with vitality changes were -0.34, -0.32, and -0.28, respectively (P < 0.001). The direct effect of treatment on change in vitality was statistically significant (68%, P = 0.010) when assessed in an indirect manner through change in sleep interference alone but not in daily or night pain solely. Path analyses suggested vitality improvement in patients with chronic pain may be secondary to improvement in pain by duloxetine. Results do not prove pain causes fatigue, but indicate in DPNP patients with fatigue that treatment of pain can improve perception of improvement in fatigue. Thus, improvement of pain may be important in the context of trying to improve fatigue in DPNP patients.

Objective: To measure rapport between medical students and standardized patients using observer ratings; to relate these ratings to students' emotional awareness and to behavior within the medical interaction; and to assess the relative validity of using excerpts of different lengths for the measurement of rapport., Methods: Third-year medical students (N=141) were videotaped during a 15-min interaction with a standardized patient, and rapport as well as other communication variables were measured using trained coders. Rapport was measured with good interrater reliability by trained coders who viewed three 1-min excerpts. Emotional awareness was measured by a test of recognizing facial expressions of emotion, self-ratings of emotional self-awareness, and peer ratings of interpersonal sensitivity. Finally, participants who viewed the videotapes while imagining themselves to be the patient (analogue patients) provided impressions of the students, including satisfaction., Results: Rapport based on all three minutes was positively correlated with accuracy in decoding facial expressions of emotion, self-reported attention to one's own emotions, peer ratings of sensitivity, communication behaviors of the medical student and standardized patient, and analogue patients' positive impressions and satisfaction. Rapport based on just the first minute of the interaction was significantly related to many of these variables., Conclusion: Rating short excerpts of behavior is a valid and efficient methodology for capturing the concept of rapport., Practice Implications: Clinicians, researchers, and educators should focus on rapport building, even very early in the medical visit.

Lymphocyte stimulation tests (LST) were performed in five dogs sensitised with ovalbumin (OVA) and seven healthy dogs. In addition, all five OVA-sensitised and two control dogs were tested after two in vivo provocations with OVA-containing eye drops. The isolated cells were suspended in culture media containing OVA and were cultured for up to 12 days. Proliferation was measured as reduction in 5,6-carboxylfluorescein diacetate succinimidyl ester (CFSE) intensity by flow cytometry on days 0, 3, 6, 9 and 12. A cell proliferation index (CPI) for each day and the area under the curve (AUC) of the CPI was calculated for each dog. All OVA-sensitised dogs demonstrated increased erythema after conjunctival OVA application. The presence of OVA-specific lymphocytes was demonstrated in 2/5 OVA-sensitised dogs before and 4/5 after in vivo provocation. Using the AUC, the difference between OVA-sensitised and control dogs was significant in all three LST before in vivo provocation (P<0.05) and borderline significant (P=0.053) in 2/3 LST after provocation. The most significant difference in CPI was observed after 9 days of culture (P=0.001). This pilot study indicates that the LST allows detection of rare antigen specific memory T-cells in dogs previously sensitised to, but not concurrently undergoing challenge by a specific antigen.

Estrogen-related receptor alpha (ERRalpha) is an orphan nuclear receptor, the expression of which correlates with negative prognosis in breast cancer. ERRalpha shares functional features with the estrogen receptor alpha (ERalpha) and its activity is modulated by the ERBB2 signaling pathway. Using genome-wide binding sites location analyses in ERalpha-positive and ERalpha-negative breast cancer cell lines, we show that ERRalpha and ERalpha display strict binding site specificity and maintain independent mechanisms of transcriptional activation. Nonetheless, ERRalpha and ERalpha coregulate a small subset of common target genes via binding either to a dual-specificity binding site or to distinct cognate binding sites located within the extended promoter region of the gene. Although ERRalpha signaling in breast cancer cells is mostly independent of ERalpha, the small fraction of common ERRalpha/ERalpha targets comprises genes with high relevance to breast tumor biology, including genes located within the ERBB2 amplicon and GATA3. Finally, unsupervised hierarchical clustering based on the expression profiling of ERRalpha direct target genes in human breast tumors revealed four main clusters that recapitulate established tumor subtypes. Taken together, the identification and functional characterization of the ERRalpha transcriptional network implicate ERRalpha signaling as a determinant of breast cancer heterogeneity.

OBJECTIVE: The purpose of this research was to evaluate the effectiveness of a comprehensive, strengths-based model of case management for clients in drug abuse treatment. METHOD: 503 volunteers from residential or intensive outpatient treatment were randomly assigned to one of three conditions of Iowa Case Management (ICM) plus treatment as usual (TAU), or to a fourth condition of TAU only. All were assessed at intake and followed at 3, 6, and 12 months. RESULTS: Clients in all four conditions significantly decreased substance use by 3 months after intake and maintained most gains over time. However, the addition of ICM to TAU did not improve substance use outcomes. CONCLUSION: Overall, the addition of case management did not significantly improve drug treatment as hypothesized by both researchers and clinicians. Some results were mixed, possibly due to the heterogeneous sample, wide range of case management activities, or difficulty retaining participants over time.

Objective: Analyzes the term "theoretical" as it applies to the area of provider-patient communication research, in order to understand better at a conceptual level what the term may mean for authors and critics., Methods: Based on literature on provider-patient communication., Results: Offers, and discusses, five definitions of the term "theoretical" as it applies to empirical research and its exposition: (1) grounding, (2) referencing, (3) design and analysis, (4) interpretation, and (5) impact. Each of these definitions embodies a different standard for evaluating the theoretical aspects of research., Conclusion: Although it is often said that research on provider-patient communication is not "theoretical" enough, the term is ambiguous and often applied vaguely. A multidimensional analysis reveals that there are several distinct ways in which empirical research can be strong or weak theoretically., Practice Implications: Researchers, educators, editors, and reviewers could use the "Five Ways" framework to appraise the theory-relevant strengths and weaknesses of empirical research and its exposition.

Background: Insufficient intake of selenium (Se) is common in many regions, and can contribute to increased susceptibility to and prolonged recovery from infectious diseases., Objective: To determine the effect of Se administration in decreasing the severity and prevalence of footrot in sheep., Animals: Thirty-eight footrot-affected and 19 nonaffected sheep from a commercial flock of known high incidence of footrot., Methods: Placebo-controlled, prospective, 15-month clinical trial. Footrot-affected sheep were randomly assigned into 2 groups (n = 19) and injected with either 5 mg Se (footrot [FR]-Se) or saline (FR-Sal) at 1-month intervals for the duration of the study. Unaffected sheep (controls) received no treatment. Sheep feet were examined, trimmed, and scored for footrot with a scale of 0 (no footrot) to 4 (extensive) at 0, 3, 6, 9, and 15 months. Sheep were also bled at time 0 and then at 3, 6, and 15 months to assess whole blood Se concentrations., Results: At time 0, control sheep (255 +/- 11 ng/mL) had higher (P < .05) whole blood Se concentrations compared with FR-Se (205 +/- 12 ng/mL) and FR-Sal (211 +/- 14 ng/mL) sheep. By 6 months, FR-Se sheep (317 +/- 9 ng/mL) had whole blood Se concentrations greater (P < .05) than both control (281 +/- 14 ng/mL) and FR-Sal (277 +/- 16 ng/mL) sheep. FR-Se ewes showed a faster decline in highest lesion score at 3 (P= .012) and 6 (P= .0036) months, and a greater decrease in the number of feet with foot score >0 at 6 (P= .020) months compared with FR-Sal ewes. Sheep with blood Se concentrations <300 ng/mL were at 3.5 times greater risk (1.1-12.1 confidence interval, odds ratio) for FR, although this relationship was only significant (P= .04) at 6 months of the study., Conclusions and Clinical Importance: In sheep with footrot, improved Se status in conjunction with routine control practices result in more rapid improvement of foot lesions.

Background: Standard open reduction and internal fixation techniques have been successful in restoring osseous alignment for bicondylar tibial plateau fractures; however, surgical morbidity, especially soft-tissue infection and wound necrosis, has been reported frequently. For this reason, several investigators have proposed minimally invasive methods of fracture reduction followed by circular external fixation as an alternative approach. To our knowledge, there has been no direct comparison of the two operative approaches., Methods: We performed a multicenter, prospective, randomized clinical trial in which standard open reduction and internal fixation with medial and lateral plates was compared with percutaneous and/or limited open fixation and application of a circular fixator for displaced bicondylar tibial plateau fractures (Schatzker types V and VI and Orthopaedic Trauma Association types C1, C2, and C3). Eighty-three fractures in eighty-two patients were randomized to operative treatment (forty-three fractures were randomized to circular external fixation and forty to open reduction and internal fixation). Follow-up consisted of obtaining a history, physical examination, and radiographs; completion of the Hospital for Special Surgery (HSS) knee score, the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), and the Short Form-36 (SF-36) General Health Survey; and recording of complication and reoperation rates., Results: There were no significant differences between the groups in terms of demographic variables, mechanism of injury, or fracture severity and/or displacement. However, patients in the circular fixator group had less intraoperative blood loss than those in the open reduction and internal fixation group (213 mL and 544 mL, respectively; p = 0.006) and spent less time in the hospital (9.9 days and 23.4 days, respectively; p = 0.024). The quality of osseous reduction was similar in the groups. There was a trend for patients in the circular fixator group to have superior early outcome in terms of HSS scores at six months (p = 0.064) and the ability to return to preinjury activities at six months (p = 0.031) and twelve months (p = 0.024). These outcomes were not significantly different at two years. There was no difference in total arc of knee motion, and the WOMAC scores at two years after the injury were not significantly different between the groups with regard to the pain (p = 0.923), stiffness (p = 0.604), or function (p = 0.827) categories. The SF-36 scores at two years after the injury were significantly decreased compared with the controls for both groups (p = 0.001 for the circular fixator group and p = 0.014 for the open reduction and internal fixation group), although there was less impairment in the circular fixator group in the bodily pain category (a score of 46) compared with the open reduction and internal fixation group (a score of 35) (p = 0.041). Seven (18%) of the forty patients in the open reduction and internal fixation group had a deep infection. The number of unplanned repeat surgical interventions, and their severity, was greater in the open reduction and internal fixation group (thirty-seven procedures) compared with the circular fixator group (sixteen procedures) (p = 0.001)., Conclusions: Both techniques provide a satisfactory quality of fracture reduction. Because percutaneous reduction and application of a circular fixator results in a shorter hospital stay, a marginally faster return of function, and similar clinical outcomes and because the number and severity of complications is much higher with open reduction and internal fixation, we believe that circular external fixation is an attractive option for these difficult-to-treat fractures. Regardless of treatment method, patients with this injury have substantial residual limb-specific and general health deficits at two years of follow-up.

We conducted a prospective, randomized, controlled trial to compare functional outcomes, complications, and reoperation rates in elderly patients with displaced intra-articular, distal humeral fractures treated with open reduction-internal fixation (ORIF) or primary semiconstrained total elbow arthroplasty (TEA). Forty-two patients were randomized by sealed envelope. Inclusion criteria were age greater than 65 years; displaced, comminuted, intra-articular fractures of the distal humerus (Orthopaedic Trauma Association type 13C); and closed or Gustilo grade I open fractures treated within 12 hours of injury. Both ORIF and TEA were performed following a standardized protocol. The Mayo Elbow Performance Score (MEPS) and Disabilities of the Arm, Shoulder and Hand (DASH) score were determined at 6 weeks, 3 months, 6 months, 12 months, and 2 years. Complication type, duration, management, and treatment requiring reoperation were recorded. An intention-to-treat analysis and an on-treatment analysis were conducted to address patients randomized to ORIF but converted to TEA intraoperatively. Twenty-one patients were randomized to each treatment group. Two died before follow-up and were excluded from the study. Five patients randomized to ORIF were converted to TEA intraoperatively because of extensive comminution and inability to obtain fixation stable enough to allow early range of motion. This resulted in 15 patients (3 men and 12 women) with a mean age of 77 years in the ORIF group and 25 patients (2 men and 23 women) with a mean age of 78 years in the TEA group. Baseline demographics for mechanism, classification, comorbidities, fracture type, activity level, and ipsilateral injuries were similar between the 2 groups. Operative time averaged 32 minutes less in the TEA group (P = .001). Patients who underwent TEA had significantly better MEPSs at 3 months (83 vs 65, P = .01), 6 months (86 vs 68, P = .003), 12 months (88 vs 72, P = .007), and 2 years (86 vs 73, P = .015) compared with the ORIF group. Patients who underwent TEA had significantly better DASH scores at 6 weeks (43 vs 77, P = .02) and 6 months (31 vs 50, P = .01) but not at 12 months (32 vs 47, P = .1) or 2 years (34 vs 38, P = .6). The mean flexion-extension arc was 107 degrees (range, 42 degrees -145 degrees) in the TEA group and 95 degrees (range, 30 degrees -140 degrees) in the ORIF group (P = .19). Reoperation rates for TEA (3/25 [12%]) and ORIF (4/15 [27%]) were not statistically different (P = .2). TEA for the treatment of comminuted intra-articular distal humeral fractures resulted in more predictable and improved 2-year functional outcomes compared with ORIF, based on the MEPS. DASH scores were better in the TEA group in the short term but were not statistically different at 2 years' follow-up. TEA may result in decreased reoperation rates, considering that 25% of fractures randomized to ORIF were not amenable to internal fixation. TEA is a preferred alternative for ORIF in elderly patients with complex distal humeral fractures that are not amenable to stable fixation. Elderly patients have an increased baseline DASH score and appear to accommodate to objective limitations in function with time.

Objective: This study evaluated whether adherence to the Strengths-Oriented Referral for Teens (SORT) model, a motivational interviewing (MI)-consistent intervention addressing ambivalence about attending treatment, positively predicted adolescents' initial-session attendance., Method: Therapist adherence was rated in 54 audiotaped SORT sessions by coders who were blind to treatment-entry status. Higher adherence scores reflected greater use of MI and solution focused language, discussion of client strengths, and dialogue with families on treatment need and options., Results: Therapist adherence during adolescent segments interacted with adolescent problem perception. Predicted probabilities of attending initial sessions increased for low-problem-perception adolescents at increasingly higher therapist adherence., Conclusions: Although replication studies are needed, the SORT model of providing MI-consistent debriefing following initial assessments appears to be a promising approach for increasing treatment entry. Initial support for the treatment-matching hypothesis was found for substance-misusing adolescents contemplating treatment entry.

Objective: We present a post-hoc analysis of the safety and efficacy of duloxetine, a selective serotonin/norepinephrine reuptake inhibitor, for treatment of diabetic peripheral neuropathic pain (DPNP) in older patients., Methods: Data from three double-blind, placebo-controlled trials in adult patients with DPNP were pooled and stratified by age (<65, >or=65 years). Patients were randomized to duloxetine (DLX) 60 mg once-daily, 60 mg twice-daily, or placebo for 12 weeks, followed by a 52-week extension phase (re-randomization to routine care or DLX 120 mg/day). Intent-to-treat analyses were used for safety and efficacy assessment., Results: In the acute phase, overall TEAE rates did not differ significantly by age. A greater percentage of older patients discontinued due to TEAEs (P<0.001), regardless of treatment group. Duloxetine improved weekly mean 24-hour average pain scores versus placebo in both age groups (P<0.01). In the extension phase, a significant therapy-by-age interaction (P<0.05) was observed in overall TEAE rate; with routine care, 86.6% of older patients had >or=1 TEAE versus 74.6% of younger patients., Conclusions: Although TEAEs more frequently lead to discontinuation in older patients, duloxetine was well tolerated and efficacious for treatment of DPNP regardless of age. These data suggest duloxetine may be beneficial for treatment of DPNP in patients>or=65.

Microglia are resident cells of the CNS that belong to the myeloid cell lineage. In experimental models of neuroinflammation, they have limited capacity to function as APCs when compared with dendritic cells (DCs). Human peripheral blood monocytes have the plasticity to differentiate into mature DCs when exposed to GM-CSF and IL-4 followed by LPS. In this study we addressed the potential of human microglia to acquire phenotypic and functional properties of mature DCs under similar inducing conditions. Treated adult and fetal microglia became CD14(low) and acquired limited expression of CD209 (DC-SIGN); they remained CD1a(-) and CD83(-), and decreased MHCII expression, suggesting that they had not achieved a complete DC phenotype. The monocyte-derived DCs efficiently promoted CD4 T cell proliferation in an allogeneic MLR, whereas differentiated adult microglia had a decreased ability to stimulate CD4 T cell proliferation compared with their untreated counterparts. Differentiated fetal microglia did support CD4 T cell proliferation, whereas untreated cells could not. Fetal and adult microglia produced significant amounts of IL-10 following differentiation but no detectable IL-12 p70, in contrast to differentiated monocytes that produced IL-12 p70. Our data indicate that neither adult nor fetal microglia acquired the full characteristic phenotype of mature stimulatory DCs when treated with DC-inducing cytokines in vitro. Moreover, such treatment, especially of adult microglia, induces functional responses that could promote an antiinflammatory environment in the CNS.

The persistence of DNA from microorganisms exposed to various concentrations of SiO2 (ranging from 0 to 3000 p.p.m.) was monitored over time. The impact of silica mineralization or silicification on the longevity of 16S rRNA and 16 s rDNA genes from whole cells of Bacillus subtilis and Escherichia coli K12 was quantified using real-time polymerase chain reaction (RT-PCR), and cells were visualized using optical microscopy. For B. subtilis, DNA longevity decreased in experiments with higher levels of SiO2 (1000 and 3000 p.p.m.), in comparison to zero or low (100 p.p.m.) levels. For B. subtilis, cell viability was greatest in the absence of silica, and markedly decreased in the presence of any concentration of silica. Survival of Escherichia coli cells, on the other hand, was not sensitive to silica in the solution. All cells died at similar rates over the 180 days they were monitored, decreasing to about 1% survival. DNA longevity for E. coli did appear to be enhanced to some degree by the presence of 1000 p.p.m. silica, but higher or lower concentrations showed no increased longevity in comparison to the no-silica control. Overall, findings of this study do not support the hypothesis that siliceous environments provide enhanced protection and preservation of DNA over time. However, results of this study do provide guidelines on the persistence of DNA that might be expected in modern silica-rich environments, which may be an important factor for proper characterization of present-day microbial communities.

Background: Physician and patient gender both influence medical communication. Nonverbal behavior is generally under-researched in the medical encounter but plays an important role for patient outcomes such as satisfaction., Objective: This article aims at identifying how specific physician nonverbal behaviors predict analogue patient satisfaction depending on physician and patient gender., Research Design: Eleven physicians in a real medical encounter were videotaped and analogue patients indicated their satisfaction with each physician while viewing the videotapes., Subjects: One hundred sixty-three university students participated (analogue patients)., Measures: From the videotapes, 17 physician nonverbal behaviors (related to face, body, voice/speech), 2 physician appearance cues, 2 characteristics of the examination room, and 1 patient behavior were coded. For each analogue patient, the correlation between each of these coded characteristics and the patient's satisfaction was calculated, across all physicians and across male and female physicians separately., Results: There was no main effect for patient gender but most coded characteristics showed different relations to patient satisfaction according to physician gender. Analogue patients were most satisfied with female physicians who behaved in line with the female gender role (eg, more gazing, more forward lean, softer voice) while still stressing their professionalism (laboratory coat, medical-looking examination room). For male physicians, satisfaction was high for a broader range of behaviors, partly related to their gender role (eg, louder voice, more distance to patient)., Conclusions: To be satisfied, patients expect female and male physicians to show different patterns of nonverbal behavior. Awareness of these gender-specific expectations should be taken into account in medical training.

Background: Tako-tsubo cardiomyopathy (idiopathic apical ballooning syndrome or ampulla cardiomyopathy) has recently been described. First recognised in Japanese patients, tako-tsubo refers to the end-systolic appearance of the left ventricle on ventriculography and its resemblance to the round bottomed, narrow necked Japanese fishing pots used to trap octopus, Case Presentation: We present two cases of female caucasian patients aged 40 and 63 years respectively admitted following severe stressful events who met the diagnostic criteria of tako-tsubo cardiomyopathy, namely acute chest pain, transient akinesis or dyskinesia of the left ventricle, new dynamic electrocardiogram changes and no significant epicardial coronary artery disease in the absence of recent head trauma, intracranial bleeding, phaeochromocytoma, myocarditis and hypertrophic cardiomyopathy. Both had elevated cardiac biomarkers. Characteristically the condition is transient and the abnormal akinesia/dyskinesia of the left ventricle has been observed to normalise within 1-month as in our patients who made full recoveries., Conclusion: Patients with tako-tsubo cardiomyopathy present with features consistent with an acute coronary syndrome and as such the syndrome is probably under-diagnosed. It may be with the introduction of primary percutaneous coronary intervention more cases are identified, sparing patients the risks of unnecessary thrombolytic therapy. Tako-tsubo cardiomyopathy should be considered in all patients presenting with acute onset chest pain and elevated cardiac biomarkers.

CD4(+)Foxp3(+) regulatory T (Treg) cells originate primarily from thymic differentiation, but conversion of mature T lymphocytes to Foxp3 positivity can be elicited by several means, including in vitro activation in the presence of TGF-beta. Retinoic acid (RA) increases TGF-beta-induced expression of Foxp3, through unknown molecular mechanisms. We showed here that, rather than enhancing TGF-beta signaling directly in naive CD4(+) T cells, RA negatively regulated an accompanying population of CD4(+) T cells with a CD44(hi) memory and effector phenotype. These memory cells actively inhibited the TGF-beta-induced conversion of naive CD4(+) T cells through the synthesis of a set of cytokines (IL-4, IL-21, IFN-gamma) whose expression was coordinately curtailed by RA. This indirect effect was evident in vivo and required the expression of the RA receptor alpha. Thus, cytokine-producing CD44(hi) cells actively restrain TGF-beta-mediated Foxp3 expression in naive T cells, and this balance can be shifted or fine-tuned by RA.

The intestinal tract is in intimate contact with the commensal microflora. Nevertheless, how commensals communicate with cells to ensure immune homeostasis is still unclear. In this study, we found that gut flora DNA (gfDNA) plays a major role in intestinal homeostasis through Toll-like receptor 9 (TLR9) engagement. Tlr9(-/-) mice displayed increased frequencies of CD4(+)Foxp3(+) regulatory T (Treg) cells within intestinal effector sites and reduced constitutive IL-17- and IFN-gamma-producing effector T (Teff) cells. Complementing this, gfDNA limited lamina propria dendritic cell-induced Treg cell conversion in vitro. Further, Treg/Teff cell disequilibrium in Tlr9(-/-) mice led to impaired immune responses to oral infection and to oral vaccination. Impaired intestinal immune responses were recapitulated in mice treated with antibiotics and were reversible after reconstitution with gfDNA. Together, these data point to gfDNA as a natural adjuvant for priming intestinal responses via modulation of Treg/Teff cell equilibrium.

Myocarditis is a rare condition that can mimic an acute coronary syndrome (ACS). We present the case of a 24-year-old male with Noonan syndrome who presented with a diarrhoeal pro-dromal illness, acute onset chest pain, elevated cardiac biomarkers and an abnormal ECG with ST elevation in the absence of obstructive coronary artery disease. The patient had acute myocarditis secondary to Campylobacter jejuni enterocolitis. Infective myocarditis is most commonly due to a viral infection. Myocarditis is very rarely due to a bacterial infection with only isolated reports of myocarditis induced by Campylobacter jejuni infection. At follow-up he remains well. Myocarditis should be considered in all patients presenting with acute onset chest pain and elevated cardiac biomarkers.

Fingolimod is a sphingosine-1-phosphate (S1P) analogue that has been used in clinical trials as a systemic immunomodulatory therapy for multiple sclerosis. Fingolimod readily accesses the central nervous system, raising the issue of its direct effects on neural cells. We assessed the effects of active fingolimod on dissociated cultures of mature, myelin-producing oligodendrocytes (OLGs) derived from adult human brain. Human OLGs express S1P receptor transcripts in relative abundance of S1P5>S1P3>S1P1, with undetectable levels of S1P4. Low doses of fingolimod (100 pmol/L to 1 nmol/L) induced initial membrane elaboration (2 days), subsequent retraction (4 days), and recurrence of extension with prolonged treatment (8 days). Higher doses (10 nmol/L to 1 mumol/L) caused the opposite modulation of membrane dynamics. Retraction was rescued by co-treatment with the S1P3/S1P5 pathway antagonist, suramin, and was associated with RhoA-mediated cytoskeletal signaling. Membrane elaboration was mimicked using the S1P1 agonist SEW2871. Fingolimod rescued human OLGs from serum and glucose deprivation-induced apoptosis, which was reversed with suramin co-treatment and mimicked using an S1P5 agonist. High doses of fingolimod induced an initial down-regulation of S1P5 mRNA levels relative to control (4 hours), subsequent up-regulation (2 days), and recurrent down-regulation (8 days). S1P1 mRNA levels were inversely regulated compared with S1P5. These results indicate that fingolimod modulates maturity- and species-specific OLG membrane dynamics and survival responses that are directly relevant for myelin integrity.

Objective: To review the literature on gender differences and issues of self-confidence in medical students and to present original research on observers' perceptions of medical student confidence., Methods: One hundred forty-one 3rd year medical students at Indiana University School of Medicine were videotaped during their objective structured clinical examination (OSCE). Trained coders rated how confident the student appeared and coded a variety of nonverbal behaviors at the beginning, middle, and end of the interaction. Analysis focused on gender differences in coders' ratings of perceived confidence., Results: Female medical students were viewed as significantly less confident than male medical students (F(1,133)=4.45, p<0.05), especially at the beginning of the interaction., Conclusion: Past research indicates that despite performing equally to their male peers, female medical students consistently report decreased self-confidence and increased anxiety, particularly over issues related to their competence. In a standardized patient interaction examination situation, female medical students also appeared significantly less confident than male medical students to independent observers., Practice Implications: Medical educators should focus on issues of female students' confidence, increasing faculty sensitivity, and publicly recognizing and discussing perceptions of confidence.

2,7-Dihydroxycadalene and lacinilene C, sesquiterpenoid phytoalexins that accumulate at infection sites during the hypersensitive resistant response of cotton foliage to Xanthomonas campestris pv. malvacearum, have light-dependent toxicity toward host cells, as well as toward the bacterial pathogen. Adaxial epidermal cells surrounding and sometimes covering infection sites turn red. The red cells exhibited 3-4-fold higher absorption at the photoactivating wavelengths of sunlight than nearby colorless epidermal cells. Red epidermal cells protected underlying palisade mesophyll cells from the toxic effects of 2,7-dihydroxycadalene plus sunlight, indicating a role for epidermal pigments in protecting living cells that surround infection sites from toxic effects of the plant's own phytoalexins. A semi-quantitative survey of UV-absorbing substances extracted from epidermal strips from inoculated and mock-inoculated cotyledons indicated that the principal increase in capacity to absorb the photoactivating wavelengths was due to a red anthocyanin and a yellow flavonol, which were identified as cyanidin-3-O-beta-glucoside and quercetin-3-O-beta-glucoside, respectively.

Background: Workable risk models for patients undergoing percutaneous coronary intervention (PCI) are needed urgently., Objective: To validate two proposed risk adjustment models (Mayo Clinic Risk Score (MC), USA and North West Quality Improvement Programme (NWQIP), UK models) for in-hospital PCI complications on an independent dataset of relatively high risk patients undergoing PCI., Setting: Tertiary centre in northern England., Methods: Between September 2002 and August 2006, 5034 consecutive PCI procedures (validation set) were performed on a patient group characterised by a high incidence of acute myocardial infarction (MI; 16.1%) and cardiogenic shock (1.7%). Two external models-the NWQIP model and the MC model-were externally validated., Main Outcome Measure: Major adverse cardiovascular and cerebrovascular events: in-hospital mortality, Q-wave MI, emergency coronary artery bypass grafting and cerebrovascular accidents., Results: An overall in-hospital complication rate of 2% was observed. Multivariate regression analysis identified risk factors for in-hospital complications that were similar to the risk factors identified by the two external models. When fitted to the dataset, both external models had an area under the receiver operating characteristic curve >or=0.85 (c index (95% CI), NWQIP 0.86 (0.82 to 0.9); MC 0.87(0.84 to 0.9)), indicating overall excellent model discrimination and calibration (Hosmer-Lemeshow test, p>0.05). The NWQIP model was accurate in predicting in-hospital complications in different patient subgroups., Conclusions: Both models were externally validated. Both predictive models yield comparable results that provide excellent model discrimination and calibration when applied to patient groups in a different geographic population other than that in which the original model was developed.

This review was undertaken to identify the evolutionary process in the current understanding of allegations of drug facilitated sexual assault (DFSA), so that those who work in this field may gain a better understanding of the complexities involved in such cases. Several definitions of DFSA are provided as well as a list of intoxicating substances which have so far been incriminated in this crime. Perception and alcohol use is addressed, whilst an examination of intoxication and victim outcomes reveals disturbing but important information which needs to be centrally placed within health education campaigns with a degree of urgency. The review identifies the effects of alcohol on sexual behaviour, drinking patterns and specific quantitative research indicating very high alcohol levels in some instances. In practical terms, suggestions are made following Operation Matisse, to address prevention, early detection and easier identification of DFSA cases so that victims' needs are prioritised and appropriately addressed.

Objective: The purpose of this study was to distinguish the contributions of CD44 expressed on bone marrow-derived and non-bone marrow-derived cells to atherosclerosis., Methods and Results: Using bone marrow chimeras, we compared the contributions of CD44 expressed on bone marrow-derived cells versus non-bone marrow-derived cells to the vascular inflammation underlying atherosclerosis. We show that CD44 in both bone marrow-derived and non-bone marrow-derived compartments promotes atherosclerosis in apoE-/- mice and mediates macrophage and T cell recruitment to lesions in vivo. We also demonstrate that CD44 on endothelial cells (ECs) as well as on macrophages and T cells enhances leukocyte-endothelial cell adhesion and transendothelial migration in vitro. Furthermore, CD44 on vascular smooth muscle cells (VSMCs) regulates their hyaluronan (HA)-dependent migration. Interestingly, in mice lacking CD44 in both compartments, where we observed the least inflammation, we also observed enhanced fibrous cap formation., Conclusions: CD44 expressed on bone marrow-derived and non-bone marrow-derived cells both promote atherosclerosis in apoE-deficient mice. Furthermore, CD44 plays a pivotal role in determining the balance between inflammation and fibrosis in atherosclerotic lesions which can impact clinical outcome in humans.

Background: Physician communication style affects patients' perceptions and behaviors. Two aspects of physician communication style, caring and dominance, are often related in that a high caring physician is usually not dominant and vice versa., Objective: This research was aimed at testing the sole or joint impact of physician caring and physician dominance on participant perceptions and behavior during the medical visit., Participants and Design: In an experimental design, analog patients (APs) (167 university students) interacted with a computer-generated virtual physician on a computer screen. Participants were randomly assigned to 1 of 4 experimental conditions (physician communication style: high dominance and low caring, high dominance and high caring, low dominance and low caring, or low dominance and high caring). The APs' verbal and nonverbal behavior during the visit as well as their perception of the virtual physician were assessed., Results: Analog patients were able to distinguish dominance and caring dimensions of the virtual physician's communication. Moreover, APs provided less medical information, spoke less, and agreed more when interacting with a high-dominant compared to a low-dominant physician. They also talked more about emotions and were quicker in taking their turn to speak when interacting with a high-caring compared to a low-caring physician., Conclusions: Dominant and caring physicians elicit different emotional and behavioral responses from APs. Physician dominance reduces patient engagement in the medical dialog and produces submissiveness, whereas physician caring increases patient emotionality.

Objective: To use funnel plots and cumulative funnel plots to compare in-hospital outcome data for operators undertaking percutaneous coronary interventions with predicted results derived from a validated risk score to allow for early detection of variation in performance., Design: Analysis of prospectively collected data., Setting: Tertiary centre NHS hospital in the north east of England., Participants: Five cardiologists carrying out percutaneous coronary interventions between January 2003 and December 2006., Main Outcome Measures: In-hospital major adverse cardiovascular and cerebrovascular events (in-hospital death, Q wave myocardial infarction, emergency coronary artery bypass graft surgery, and cerebrovascular accident) analysed against the logistic north west quality improvement programme predicted risk, for each operator. Results are displayed as funnel plots summarising overall performance for each operator and cumulative funnel plots for an individual operator's performance on a case series basis., Results: The funnel plots for 5198 patients undergoing percutaneous coronary interventions showed an average observed rate for major adverse cardiovascular and cerebrovascular events of 1.96% overall. This was below the predicted risk of 2.06% by the logistic north west quality improvement programme risk score. Rates of in-hospital major adverse cardiovascular and cerebrovascular events for all operators were within the 3sigma upper control limit of 2.75% and 2sigma upper warning limit of 2.49%., Conclusion: The overall in-hospital major adverse cardiovascular and cerebrovascular events rates were under the predicted event rate. In-hospital rates after percutaneous coronary intervention procedure can be monitored successfully using funnel and cumulative funnel plots with 3sigma control limits to display and publish each operator's outcomes. The upper warning limit (2sigma control limit) could be used for internal monitoring. The main advantage of these charts is their transparency, as they show observed and predicted events separately. By this approach individual operators can monitor their own performance, using the predicted risk for their patients but in a way that is compatible with benchmarking to colleagues, encapsulated by the funnel plot. This methodology is applicable regardless of variations in individual operator case volume and case mix.

The purpose of this study was to evaluate the effectiveness of outpatient substance abuse treatment for youth with high traumatic stress compared to youth without high traumatic stress in substance abuse treatment centers across the United States. The data for this study were gathered using a longitudinal survey design with purposive sampling from nine drug treatment delivery systems across the United States participating in the cooperative grant Strengthening Communities for Youth (SCY) awarded by SAMHSA's Center for Substance Abuse Treatment (CSAT) between September 2002 and June 2006. Follow-up assessments were conducted with the youth at three,six, and 12 months following intake. Traumatized youth responded to outpatient treatment in a similar pattern when compared to nontraumatized youth, although the traumatized youth had consistently higher scores on substance use frequency and substance problems scales than nontraumatized youth throughout the study. Current empirically validated treatments for adolescent substance abuse do not prepare the practitioner for trauma-informed practice or specifically address trauma-informed recovery. Based on our results, we advocate for the development and integration of trauma-informed practice within substance abuse treatment for adolescents to help them recover from trauma and substance abuse issues.

This study compared the characteristics and treatment outcomes of rural adolescents with urban adolescents in substance abuse treatment programs in CSAT's Strengthening Communities for Youth (SCY) initiative. Using data from ten SCY programs nationally, the authors classified adolescents as rural or urban using Rural-Urban Commuting Area (RUCA) codes. We then evaluated changes in substance use frequency and substance-related problems at three, six, and 12 months after baseline assessments for the two sites that treated rural (n = 59) and urban (n = 345) youth in outpatient settings. Data were analyzed using a two-part mixed effects model for zero-saturated dependent variables. At treatment intake, rural youth exhibited greater problem severity on a number of substance abuse and mental health indices. From intake to the 12-month follow-up point, the percentages of both urban and rural youth who reported abstinence increased significantly. Both rural and urban youth also reported fewer problems due to substance use over time, but differences between groups were not consistent. Overall, treatment appears equally effective for both rural and urban adolescents. As few rural youth obtained treatment, we encourage funding agencies and treatment providers to consider innovative ways for providing services in rural areas and addressing gaps in primary prevention, early identification, and continuing care.

Background: Rescue angioplasty (rPCI) for failed fibrinolysis is associated with a low mortality if successful, but a high mortality if it fails. The latter may reflect a high-risk group or harm in some patients. Predictors of success or failure of rPCI may aid selection of patients to be treated., Methods: Unselected patients referred for rPCI from March 1994 to March 2005 were studied to determine the predictors of a failed procedure and 1-year mortality., Results: Of 440 patients undergoing emergency coronary angiography for failed fibrinolysis (1-year mortality 18%), 101 had thrombolysis in myocardial infarction flow grade (TFG) 3 in the infarct-related vessel. rPCI was attempted in 318 of 339 patients with 75 years, shock, and final TFG < 3 were independent predictors of 1-year mortality., Conclusions: Cardiogenic shock is an independent predictor of a failed rPCI. Age group >75 years and shock were the only independent clinical predictors of 1-year mortality. These clinical variables may help in selecting patients for either a strategy of rescue angioplasty after failed fibrinolysis, or in selecting specific patients who might do better with a policy of primary angioplasty., (Copyright 2008 Wiley-Liss, Inc.)

The development of coronary artery disease involves a complex interplay between environmental and genetic factors, with premature coronary artery disease having a strong genetic component. We present the case a pair of monozygotic identical twins presenting near simultaneously with coronary artery disease and identical atherosclerotic lesions despite significant differences in environmental risk factors and being divided geographically by 12,000 miles. This is of enormous importance and not merely curiosity value as it will have implications for the prevention of coronary artery disease, provide an opportunity for the development of new therapeutic strategies, and aid targeted primary prevention through family screening.

This longitudinal study examined whether youth with high traumatic stress (HTS) respond differently to outpatient substance abuse treatment compared to youth without HTS at intake, and at 3 and 6 months following intake. Data were analyzed using a mixed-effects two-part model to fit repeated data with zero saturation. Clients in both groups significantly increased their odds of abstinence and full symptom remission of substance problems from baseline to 6 months. Of youth still using substances, the group with HTS reduced substance use significantly more than substance users without HTS. Recommendations for future research are provided.

Two studies examined motivation and content domain as possible influences on sex differences in interpersonal sensitivity. Although much research has found women to excel on tasks measuring interpersonal sensitivity, most of the tasks have measured accuracy in female-relevant domains such as emotion. The present studies measured interpersonal sensitivity, defined as accurate recall of another person, for both female-relevant and male-relevant content domains and also included motivational manipulations intended to influence men and women differently. Study 1 measured accuracy of recalling information in a written vignette about a person, and Study 2 measured accuracy of recalling details about an interaction partner. Both studies supported hypotheses about domain specificity and gender-relevant motivation. However, even for male-stereotypic content and for tasks framed to favor men's motivation to perform well, men's accuracy never exceeded women's.

Peer influence and peer selection have both been linked to the smoking behavior of adolescents. The present investigation uses social network analysis methodology to explore the simultaneous effects of both processes on adolescent smoking and smoking susceptibility over two time periods. Results suggest the effects of friendship selection in 6th grade on smoking behavior in 7th grade were primarily direct. Selecting smokers as friends in 6th grade predicted both smoking and smoking susceptibility in 7th grade, and selecting susceptibles predicted future friendship selection and peer influence. Influence processes were indirectly related to smoking. Smokers' influence in 6th grade predicts the selection of smokers as friends in 7th grade. Smokers' influence also demonstrated a protective effect when ties were not reciprocated.

Since the identification of the osteogenic protein-1 (OP-1) gene, also called bone morphogenetic protein-7 (BMP-7), almost 20 years ago, OP-1 has become one of the most characteristic members of the BMP family. The biological activity of recombinant human OP-1 has been defined using a variety of animal models. These studies have demonstrated that local implantation of OP-1 in combination with a collagen matrix results in the repair of critical size defects in long bones and in craniofacial bones and the formation of bony fusion masses in spinal fusions. Clinical trials investigating long bone applications have provided supportive evidence for the use of OP-1 in the treatment of open tibial fractures, distal tibial fractures, tibial nonunions, scaphoid nonunions and atrophic long bone nonunions. Clinical studies investigating spinal fusion applications have provided supportive evidence for the use of OP-1 in posterolateral lumbar models and compromised patients as an adjunct or as a replacement for autograft. Both long bone repair and spinal fusion studies have demonstrated the efficacy and safety of OP-1 by clinical outcomes and radiographic measures. Future clinical investigations will be needed to better define variables, such as dose, scaffold and route of administration. Clearly the use of BMPs in orthopaedics is still in its formative stage, but the data suggest an exciting and promising future for the development of new therapeutic applications.

Four studies measure participants' accuracy in remembering, without forewarning, their own nonverbal behavior after an interpersonal interaction. Self-accuracy for smiling, nodding, gazing, hand gesturing, and self-touching is scored by comparing the participants' recollections with coding based on videotape. Self-accuracy is above chance and of modest magnitude on average. Self-accuracy is greatest for smiling; intermediate for nodding, gazing, and gesturing; and lowest for self-touching. It is higher when participants focus attention away from the self (learning as much as possible about the partner, rearranging the furniture in the room, evaluating the partner, smiling and gazing at the partner) than when participants are more self-focused (getting acquainted, trying to make a good impression on the partner, being evaluated by the partner, engaging in more self-touching). The contributions of cognitive demand and affective state are discussed.

Unlabelled: The impact of chronic coronary obstructions on resting blood flow in stable cardiac patients and the response to percutaneous coronary intervention (PCI) using the TIMI frame count method has not been well documented. We studied the impact of coronary artery stenosis severity on the corrected TIMI frame count (cTFC) in chronically stenosed coronary arteries. We prospectively and quantitatively determined the impact of stenting on the cTFC during elective PCI., Methods: In substudy 1, analysis was performed to obtain the mean cTFC for arteries with <50% stenosis (Group A), 51-75% stenosis (Group B), 76-85% stenosis (Group C1), 86-95% stenosis (Group C2) and 96-99% stenosis (Group C3). In substudy 2, the cTFC and quantitative coronary angiography were performed pre- and post-PCI., Results: In substudy 1, the cTFC increased exponentially beyond a diameter stenosis of 75% (P < 0.01). However there was no significant difference in the cTFC for coronary arteries with <75% stenosis. In substudy 2, the overall pre- and poststenting cTFC was 17.1 +/- 11.7 and 7.8 +/- 2.7 (P < 0.01) and the TFC index [calculated by dividing the mean cTFC for the relevant artery by the mean cTFC for the corresponding coronary artery in a previously derived control group in our laboratory] was 1.6 +/- 1 and 0.7 +/- 0.2 (P = < 0.01), respectively., Conclusion: We have demonstrated that there was a significant increase in the cTFC when the coronary artery stenosis was more than 75% reflecting significant flow abnormalities at this degree of stenosis in chronically diseased coronary arteries. Following stenting there is a significant improvement in the cTFC, which is better than the cTFC for arteries with normal flow, suggesting early hyperaemia., ((c) 2007 Wiley-Liss, Inc.)

Objective: The present study aimed to investigate the effect of physician sex and physician communication style on patient satisfaction. In real medical visits, physician sex and physician communication style are confounded variables. By using the virtual medical visit paradigm, we were able to disentangle the two variables and study their separate and/or joint effects on patient satisfaction., Method: In an experimental design, analogue patients (167 students) interacted with a computer-generated virtual physician on a computer screen. The patients' satisfaction during the visit was assessed., Results: Depending on the sex composition of the dyad, physician communication style affected analogue patients' satisfaction differently. For instance, in male-male dyads, physician communication style did not affect the patients' satisfaction, whereas in female-female dyads, analogue patients were more satisfied when the physician adopted a caring as opposed to a non-caring communication style., Conclusion: Sex of the physician and sex of the patient moderate how different physician communication styles affect patient satisfaction. In particular, a female-sex role congruent communication style leads to higher patient satisfaction when women see a female physician., Practice Implications: Physician communication training cannot be one size fits all. Rather female and male physicians should obtain different training and they need to be made aware of the fact that female and male patients harbor different expectations toward them.

To maintain immune homeostasis, the intestinal immune system has evolved redundant regulatory strategies. In this regard, the gut is home to a large number of regulatory T (T reg) cells, including the Foxp3(+) T reg cell. Therefore, we hypothesized that the gut environment preferentially supports extrathymic T reg cell development. We show that peripheral conversion of CD4(+) T cells to T reg cells occurs primarily in gut-associated lymphoid tissue (GALT) after oral exposure to antigen and in a lymphopenic environment. Dendritic cells (DCs) purified from the lamina propria (Lp; LpDCs) of the small intestine were found to promote a high level of T reg cell conversion relative to lymphoid organ-derived DCs. This enhanced conversion by LpDCs was dependent on TGF-beta and retinoic acid (RA), which is a vitamin A metabolite highly expressed in GALT. Together, these data demonstrate that the intestinal immune system has evolved a self-contained strategy to promote T reg cell neoconversion.

Chromodomain/helicase/DNA-binding domain (CHD) proteins have been identified in a variety of organisms. Despite common features, such as their chromodomain and helicase domain, they have been described as having multiple roles and interacting partners. However, a common theme for the main role of CHD proteins appears to be linked to their ATP-dependent chromatin-remodeling activity. Their actual activity as either repressor or activator, and their cell or gene specificity, is connected to their interacting partner(s). In this minireview, we attempt to match the members of the CHD family with the presence of structural domains, cofactors, and cellular roles in the regulation of gene expression, recombination, genome organization, and chromatin structure, as well as their potential activity in RNA processing.

Recent biochemical studies evaluated the affinity of histones to DNA in the context of nucleosome core particle (NCP). These have indicated a concentration-dependence for nucleosome stability. However, when studying chromatin the preferred templates are nucleosome arrays (NA) and not the NCP. Biochemical methods are poorly suited for structural analysis of chromatin. To overcome that technical hindrance, and investigate the effect of concentration on stability of the histone-DNA interactions, we have applied the multigel Quantitative Agarose Gel Electrophoresis (QAGE) method to in vitro-assembled nucleosomal arrays. The results demonstrated the method to be extremely valuable for the evaluation of the effect of low concentration on NA. However, QAGE is a fairly time-demanding and complex method. To maximize the efficiency of use of this technology, we devised a protocol that allowed for multiple sets of templates to be analyzed simultaneously. Briefly, samples can be loaded at regular intervals and analyzed individually for their molecular composition. The technique presented in this study describes the calibration steps and proof of concept necessary to validate the use of multiple loading of multigel to evaluate the composition of nucleosomal arrays as a function of concentration.

Unlabelled: The intra-aortic balloon pump (IABP) is the most commonly used temporary cardiac assist device. The precise role and the mechanism of any benefit in high-risk patients undergoing percutaneous coronary intervention (PCI) have not been fully determined. We hypothesized that the use of an IABP following PCI in high-risk non-shocked patients would immediately increase coronary blood flow, tissue perfusion and hence preserve left ventricular function., Methods: Predefined high-risk, but non-shocked, patients were randomized to either an IABP or no IABP following PCI. Angiography was performed pre-PCI, immediately post-PCI and 10 minutes after the completion of the procedure. TIMI flow grade (TFG), TIMI frame count (TFC) and myocardial blush grade (MBG) were measured. Echocardiographic wall motion index (WMI) was measured on days 1 and 30 following PCI., Results: Of 33 patients, 17 received IABP and 16 did not. At final angiography, the TFG was 2.8 +/- 0.7 and 2.9 +/- 0.3 (p = 0.6), the TFC was 19.9 +/- 23 and 16.9 +/- 16.9 (p = 0.7), and the MBG was 2.5 +/- 0.9 and 2.5 +/- 0.7 (p = 0.9) in the IABP and the no-IABP arms. The WMI on day 1 was 1.7 +/- 0.4 and 1.7 +/- 0.4 (p = 0.7), and on day 30, it was 1.5 +/- 0.4 and 1.5 +/- 0.4 (p = 0.9). There was no difference in the total sum of ST-segment elevation prior to PCI (12.6 +/- 7.7 vs. 13.5 +/- 7.9; p = 0.8), nor in the summed ST change in subsequent electrocardiograms (ECGs) to 48 hours in both of the groups., Conclusion: Whether an IABP is of any benefit in non-shocked, but high-risk, patients undergoing PCI remains to be established, but any potential benefit does not appear to be associated with early improvement in coronary flow. Whether the insertion of an IABP improves coronary flow beyond 10 minutes is not known. However, the IABP did not significantly affect subsequent left ventricular wall motion index or ECG ST-segment resolution in this study.

Object: Selective dorsal rhizotomy (SDR) has been shown to provide considerable benefit to children with spastic cerebral palsy (CP). The authors sought to evaluate the risks of postoperative spinal deformities in patients following SDR., Methods: All patients who underwent SDR at McGill University between 1991 and 2001 were identified. Hospital charts and radiographic spinal studies (both preoperative and the latest postoperative) were systematically reviewed. Univariate and multivariate regression analyses were conducted to test all independent variables of potential interest to determine risk factors more likely to be associated with spinal deformity. There were 98 patients whose mean age at surgery was 5.1 years; the mean radiographic follow-up duration was 5.8 years. Thirty-nine (44.8%) of 87 patients in whom postoperative weight-bearing radiographs were obtained had mild scoliosis, and 17 in whom standing radiographs were acquired had hyperlordosis. In all, 18 of 94 patients (19.1%) who had postoperative radiographs on which the lumbosacral junction was visible were found to have spondylolisthesis. Regression analysis identified the severity of preoperative CP as an important predictor, and less ambulatory patients were more likely to have scoliotic curves. Younger age at surgery and male sex were factors associated with a lower rate of hyperlordosis. Spondylolisthesis developed only in ambulatory children. None of the patients experienced clinically significant deficits., Conclusions: There was a high rate of radiologically documented deformities in patients with CP who underwent SDR. Ambulatory function, CP severity, age at surgery, and sex may be contributing factors.

Background: Early (30 days) and midterm (6 months) clinical outcomes in trials comparing rescue angioplasty (rescue percutaneous coronary intervention [rPCI]) with conservative treatment of failed fibrinolysis complicating ST-segment elevation myocardial infarction have shown variable results. Whether early rPCI confers late (up to 3 years) clinical benefits is not known., Methods: The MERLIN trial compared rPCI and a conservative strategy in patients with failed fibrinolysis complicating ST-segment elevation myocardial infarction. Three hundred seven patients with electrocardiographic evidence of failure to reperfuse at 60 minutes were included. Patients in cardiogenic shock were excluded. Thirty-day and 1-year results have been reported. Results of 3 years of follow-up are presented., Results: Three-year mortality in the conservative arm and rPCI, respectively, was 16.9% versus 17.6% (P = .9, relative difference [RD] -0.8, 95% CI [-9.3 to 7.8]). Death rates were similar (3.9% vs 3.2%) between 1- and 3-year follow-up, respectively. The incidence of the composite secondary end point of death, reinfarction, stroke, unplanned revascularization, or heart failure was significantly higher in the conservative arm (64.3% vs 49%, P = .01, RD 15.3, 95% CI [4.2-26]). There was no significant difference in the rate of reinfarction (0.7% vs 0.7%) or heart failure (1.3% vs 2.7%) between 1 and 3 years between the conservative and rPCI arms, respectively. The incidence of subsequent unplanned revascularization at 3 years was significantly higher in the conservative arm (33.8% vs 14.4%, P < .01, RD 19.4, 95% CI [10-28.7]), most of which occurred within 1 year; the rates between 1 and 3 years were 3.9% in the conservative arm versus 2% in the rPCI arm. There was a trend toward fewer strokes in the conservative arm at 3 years (conservative arm 2.6% vs rPCI 6.5%, P = .1, RD -3.9%, 95% CI [-9.4 to 0.8]), with similar stroke rates (1.3% vs 1.3%) between 1- and 3-year follow-up., Conclusions: Rescue angioplasty did not confer a late survival advantage at 3 years. The composite end point occurred less often in the rPCI arm mainly because of fewer unplanned revascularization procedures in the early phase of follow-up. The highest risk of clinical events in patients with failed reperfusion is in the first year, beyond which the rate of clinical events is low.