University of Pittsburgh at Greensburg

Cytokines have been proposed as inducers of beta-cell damage in human insulin-dependent diabetes mellitus via the generation of nitric oxide (NO). This concept is mostly based on data obtained in rodent pancreatic islets using heterologous cytokine preparations. The present study examined whether exposure of human pancreatic islets to different cytokines induces NO and impairs beta-cell function. Islets from 30 human pancreata were exposed for 6-144 h to the following human recombinant cytokines, alone or in combination: IFN-gamma (1,000 U/ml), TNF-alpha (1,000 U/ml), IL-6 (25 U/ml), and IL-1 beta (50 U/ml). After 48 h, none of the cytokines alone increased islet nitrite production, but IFN-gamma induced a 20% decrease in glucose-induced insulin release. Combinations of cytokines, notably IL-1 beta plus IFN-gamma plus TNF-alpha, induced increased expression of inducible NO synthase mRNA after 6 h and resulted in a fivefold increase in medium nitrite accumulation after 48 h. These cytokines did not impair glucose metabolism or insulin release in response to 16.7 mM glucose, but there was an 80% decrease in islet insulin content. An exposure of 144 h to IL-1 beta plus IFN-gamma plus TNF-alpha increased NO production and decreased both glucose-induced insulin release and insulin content. Inhibitors of NO generation, aminoguanidine or NG-nitro-L-arginine, blocked this cytokine-induced NO generation, but did not prevent the suppressive effect of IL-1 beta plus IFN-gamma plus TNF-alpha on insulin release and content. In conclusion, isolated human islets are more resistant to the suppressive effects of cytokines and NO than isolated rodent islets. Moreover, the present study suggests that NO is not the major mediator of cytokine effects on human islets.

STR multiplexes have been indispensable for the efficient genotyping of forensic samples. The PowerPlex 16 System contains the coreCODIS loci, D3S1358, D5S818, D7S820, D8S1179, D13S317, D16S539, D18S51, D21S11, CSF1PO, FGA, THOI, TPOX, vWA, the sex determinant locus, amelogenin, and two pentanucleotide STR loci, Penta D and Penta E. This multiplex satisfies the locus requirements for most national databases and is the most efficient currently available system due to its single PCR amplification. To provide the groundwork for judicial acceptance, including the publication of primer sequences, and to evaluate laboratory-to-laboratory variation, a developmental validation for casework on this commercially available system was performed in 24 laboratories and produced the following conclusions. Amplification was reliable on a variety of thermal cyclers and product could be analyzed on either an ABI PRISM 310 Genetic Analyzer or an ABI PRISM 377 DNA Sequencer. Genotyping using single source samples was consistent between 0.25 and 2 ng of input DNA template with a few laboratories obtaining complete genotypes at 0.0625 ng. However, heterozygote allele imbalance (<60% peak height balance) caused by stochastic effects was observed at a rate of 13% with 0.125 ng DNA and 22% at 0.0625 ng DNA. Mixture analyses were done using a total of 1 ng of DNA template. Most alleles were detected in mixtures of 4 to 1 and some minor alleles were detected in mixtures of 19 to 1. Optimum amplification cycle number was dependent on the sensitivity of the detection instrument used and could also be adjusted to accommodate larger amounts of DNA on solid supports such as FTA paper. Reaction conditions including volume, annealing temperature, and concentrations of primer, AmpliTaq Gold, and magnesium were shown to be optimal yet robust enough to withstand moderate variations without affecting genotype analysis. Environmental, matrix and standard source analyses revealed an ability to obtain complete genotypes in all sample types except those exposed to 80 degrees C for 12-48 days. Finally, comparison of genotype results from the PowerPlex 16 System with other commercially available systems on non-probative reference and forensic samples showed consistent results.

This article presents an evaluation of the construct validity of the Maslach Burnout Inventory (MBI). The authors base this critique on previously published findings and data collected through five studies carried out during an eight-year period, for which 328 social workers acted as respondents. Factor analyses and correlational studies designed to test predictions provided fairly consistent evidence for the utility of the MBI subscale measures of emotional exhaustion, personal accomplishment, and depersonalization. Additional analyses supported a reconceptualization of burnout and the MBI, one that regards exhaustion as the essence of burnout and treats accomplishment and depersonalization as related variables, but not as elements of burnout.

In a four‐wave panel study the coping styles of case managers hired to work with seriously and persistently mentally ill clients were measured at entry to the job. Workers' degree of stress, strain and negative consequences, such as burnout, job dissatisfaction, physical symptoms, intention to quit and life dissatisfaction, were assessed at subsequent time periods (three, 12 and/or 18 months later). Depending on time period and outcome variable studied, the effect of coping was examined in between 39 and 51 workers. The results showed that control ‐oriented coping strategies clearly acted as work stress buffers, and that those who relied exclusively on avoidance coping strategies reported higher general levels of negative consequences three months later. Implications were discussed for (a) the measurement of coping, (b) conceptions of coping styles and flexibility, and (c) programmes for assisting workers to deal with burnout arising from challenging work environments.

Abstract Major investigative interviewing protocols such as the Cognitive Interview recommend that investigators build rapport with cooperative adult witnesses at the beginning of a police interview. Although research substantiates the benefits of rapport‐building on the accuracy of child witness reports, few studies have examined whether similar benefits apply to adult witnesses. The present study investigated whether verbal rapport‐building techniques increase adult witness report accuracy and decrease their susceptibility to post‐event misinformation. One‐hundred eleven college adults viewed a videotaped mock‐crime, received post‐event misinformation (or correct information) about the crime, and were subsequently interviewed by a research assistant who built rapport (or did not build rapport) before recalling the mock‐crime. Results indicated that rapport‐building increased the quality of witness recall by decreasing the percentage of inaccurate and misinformation reported, particularly in response to open‐ended questions. We discuss implications and recommendations for law enforcement. Copyright © 2011 John Wiley & Sons, Ltd.

In a study of 125 mothers, parental stress was associated with lower role satisfaction and maternal self-esteem and with higher psychological and somatic symptomatology for those mothers with less social support. In addition, more highly educated mothers were found to be less affected by parental stress. Theoretical and policy implications of the findings are discussed.

Hepatic retransplantation is controversial because the results are inferior to primary transplants and organs are so scarce. To determine the factors that are associated with poor outcome within the first year following retransplantation, we performed a multivariate analysis, using stepwise logistic regression, of 418 hepatic retransplantations performed at a single institution from November 1987 to December 1993. The minimum follow-up was 1 year. Seven variables were found to be independently associated with subsequent graft failure (defined as either patient death or retransplantation): donor age (odds ratio 2.2 for each 10-year increase over age 45, 95% CI 1.3 to 3.7), female donor sex (odds ratio 1.7, 95% CI 1.05 to 2.7), recipient age (odds ratio 1.6 for each 10-year increase over age 45,95% CI 1.2 to 2.8), need for preoperative mechanical ventilation (odds ratio 1.8, 95% CI 1.1 to 2.9), pretransplant serum creatinine (odds ratio 1.24 for each increase of 1 mg/dl, 95% CI 1.1 to 1.4), pretransplant total serum bilirubin (odds ratio 1.4 for each 10-mg/dl increase over 15 mg/dl, 95% CI 1.1 to 1.8), and the primary immunosuppressant, using tacrolimus as the reference category (odds ratio for cyclosporine-based immunosuppression 3.9, 95% CI 2.3 to 6.8). Although not part of the logistic regression model, the timing of retransplantation was also found to be important, with the overall probability of failure increasing from 0.58 on day 0 to a peak of 0.8 on day 38 and decreasing slowly after that. The implications of these results regarding the appropriateness of retransplantation are discussed.

) treatment groups. This study demonstrates the efficacious bridging of a long peripheral nerve gap in a nonhuman primate model using an acellular, biodegradable nerve conduit.

Recurrent Clostridium difficile infection (CDI) occurs in up to 35% of patients. Recurrences can be due to either relapse with the same strain or reinfection with another strain. In this study, multilocus variable-number tandem-repeat analysis (MLVA) was performed on C. difficile isolates from patients with recurrent CDI to distinguish relapse from reinfection. In addition, univariate and multivariate analyses were performed to identify risk factors associated with relapse. Among patients with a single recurrence, relapse due to the original infecting strain was more prevalent than reinfection and the interval between episodes was shorter than among patients who had reinfections. Among patients with >1 recurrence, equal distributions of relapse and reinfection or a combination of the two episode types were observed. Initial infection with the BI/NAP1/027 epidemic clone was found to be a significant risk factor for relapse. This finding may have important implications for patient therapy. Classification of recurrent CDI episodes by MLVA can be utilized to make informed patient care decisions and to accurately define new CDI cases for infection control and reimbursement purposes.

A national survey was used to explore the potential for resilience among family members of people with mental illness. The sample included 131 family members: mothers, fathers, wives, husbands, sisters, brothers, daughters, sons, and extended family members. Responding to open-ended questions, participants were asked to describe any family, personal, or consumer strengths that had developed as a result of the mental illness. Family resilience was reported by 87.8% of participants. Personal resilience was reported by 99.2%; and consumer resilience by 75.6%. Components of these composite scores were identified. Implications of these findings are discussed, and suggestions for professional practice are offered.

Possible relationships among dietary antioxidants, oxidative status, and placental retention were investigated in periparturient dairy cows. During 6 wk prepartum, 16 cows each were given daily by capsule 1000 IU of vitamin E, 3 mg of Se, both vitamin E and Se, or neither (control). alpha-Tocopherol in serum and fast-acting antioxidants in plasma increased, but, in red blood cells, thiobarbituric acid-reactive substances decreased during the last 6 wk before parturition in cows given vitamin E. These measurements were unaffected by supplementation of Se. Cows that had retained placenta > or = 12 h had lower fast-acting antioxidants in plasma and glutathione peroxidase in red blood cells up to 2 wk before calving than did cows that shed fetal membranes in < 12 h. Results suggest that inadequate dietary antioxidants may increase oxidative stress, production of lipid peroxides, and incidence of retained fetal membranes in dairy cows.

Rapport-building is perceived by law enforcement as an essential ingredient to a successful investigative interview. Despite its professed importance and longstanding recommendation within major interviewing guidelines (e.g., the Cognitive Interview, the Army Field Manual), empirical studies have only recently examined its impact on cooperative adult witnesses and criminal suspects. To accommodate the burgeoning interest and corresponding research on rapport-building, this article reviews recent empirical literature on its role and effectiveness during investigative interviews. First, this review summarizes different definitions of rapport in clinical and investigatory contexts and the various rapport-building techniques recommended and used with witnesses and suspects. Second, this review synthesizes empirical research that has investigated the effects of rapport-building on cooperative witness accounts and its impact on the diagnostic value of information retrieved from criminal suspects. This review concludes with a discussion of public policy implications and recommendations for researchers and practitioners.

A randomized controlled trial of CMV-IVIG (cytomegalovirus-intravenous immunoglobulin) for prevention of Epstein Barr virus (EBV) posttransplant lymphoproliferative disease (PTLD) in pediatric liver transplantation (PLTx) recipients was begun in Pittsburgh and subsequently expanded to four additional sites. Protocol EB viral loads were obtained in a blinded fashion; additional loads could be obtained for clinical indications. Patients were followed for 2 years post-LTx. Eighty-two evaluable patients (39 CMV-IVIG, 43 placebo) developed 18 episodes of EBV disease (7 CMV-IVIG, 11 placebo) including nine cases of PTLD (three CMV-IVIG, six placebo). No significant differences were seen in the adjusted 2-year EBV disease-free rate (CMV-IVIG 79%, placebo 71%) and PTLD-free rate (CMV-IVIG 91%, placebo 84%) between treatment and placebo groups at 2 years (p > 0.20). The absence of significant effect of CMV-IVIG may be explained by a lack of efficacy of the drug or limitations of sample size.

Alpha-synuclein is a presynaptic protein strongly implicated in Parkinson's disease (PD). Because dopamine neurons are invariably compromised during pathogenesis in PD, we have been exploring the functions of alpha-synuclein with particular relevance to dopaminergic neuronal cells. We previously discovered reduced tyrosine hydroxylase (TH) activity and minimal dopamine synthesis in stably-transfected MN9D cells overexpressing either wild-type or A53T mutant (alanine to threonine at amino acid 53) alpha-synuclein. TH, the rate-limiting enzyme in dopamine synthesis, converts tyrosine to l-dihydroxyphenylalanine (L-DOPA), which is then converted to dopamine by the enzyme, aromatic amino acid decarboxylase (AADC). We confirmed an interaction between alpha-synuclein and AADC in striatum. We then sought to determine whether wild-type or A53T mutant alpha-synuclein might have affected AADC activity in dopaminergic cells. Using HPLC with electrochemical detection, we measured dopamine and related catechols after L-DOPA treatments to bypass the TH step. We discovered that while alpha-synuclein did not reduce AADC protein levels, it significantly reduced AADC activity and phosphorylation in our cells. These novel findings further support a role for alpha-synuclein in dopamine homeostasis and may explain, at least in part, the selective vulnerability of dopamine neurons that occurs in PD.

OBJECTIVE: The purpose of this study was to compare outcomes of radioactive seed localization (RSL) versus wire localization using surgical margin size, reexcision and reoperation rates, specimen size, radiology resource utilization, and cosmesis as measures. MATERIALS AND METHODS: Patients who underwent RSL before segmental mastectomy from April 1, 2011, to March 1, 2012, for biopsy-proven cancer were selected. Each was matched using tumor size, type, and surgeon to a wire localization control case, resulting in 232 cases. Width of the closest surgical margin, reexcision rate, and reoperation rate were compared as were the ratios of tumor volume to initial surgical specimen volume and tumor volume to all surgically excised volume (including reexcisions and reoperations). Cosmetic outcome was analyzed by comparison of Harvard scores and specimen volume with breast volume. Radiology resource utilization was compared before and after RSL implementation. RESULTS: No significant differences between methods were found in closest surgical margin (RSL mean, 0.45 cm; wire localization mean, 0.45 cm; p=0.972), reexcision rate (RSL mean, 21.1%; wire localization mean, 26.3%; p=0.360), reoperation rate (RSL, 11.4%; wire localization, 12.7%; p=0.841), ratio of the tumor volume to initial surgical specimen volume (RSL mean, 0.027; wire localization mean, 0.028; p=0.886), ratio of the tumor volume to total volume resected (RSL mean, 0.024; wire localization mean, 0.024; p=0.997), or in clinical or computed cosmesis scores (clinical p=0.5; calculated p=0.060). There was a 34% increase in scheduled biopsy slot utilization, 50% savings in time spent scheduling, and a 4.1-day average decrease in biopsy wait time after RSL institution. CONCLUSION: RSL is an acceptable alternative to wire localization and offers significant improvements in workflow.

The interrelationship and reliability of three different activity measures were examined in 76 postmenopausal women. The women wore Large Scale Integrated (LSI) activity monitors, completed the Paffenbarger Activity Survey, and completed 3-day food logs for determination of caloric intake/expenditure. The Paffenbarger survey was assessed twice, a year apart. The results indicated that caloric intake was a very poor index of activity. The LSI activity monitoring and Paffenbarger survey were both effective, reliable measures of physical activity. However, they appeared to measure somewhat different aspects of physical activity. The LSI measured physical activity associated with movement, whereas the surveys measured the intensity component of energy expenditure. The research indicated that it is important to evaluate the characteristics of the activity of interest in order to select a physical activity tool for assessing activity patterns in older women.

Forty in-depth interviews of heterosexual parents of children 5 five years of age and younger are analyzed using a qualitative grounded theory approach to understand how couples coproduce fatherhood within their day-to-day relationships and in social, cultural, and economic contexts. The analysis identifies the construct "responsivity" as a central process through which, to varying degrees, fathers are aware of the needs of their wives and children and able to take an active part in meeting them. Three groups of fathers are examined according to their level of responsivity: low, moderate, and high. Factors influencing degree of father responsivity include gender constructions, power and the wife's influence, attunement, work schedules, and emotional tradeoffs. Implications for practice are suggested.

Most investigative interviewing protocols recommend building rapport with cooperative adult witnesses to increase the accuracy of their reports. Although a few recent studies support the benefits of rapport building on adult witness recall, no study has examined whether the timing of rapport in relation to post-event misinformation affects recall accuracy, and whether these effects are related to witness anxiety levels throughout the interview. The present study provided two hundred and thirty-three undergraduates with a videotaped mock crime followed by building high or low rapport either before or after they received post-event misinformation. All witnesses were then interviewed about the mock crime. Results indicated that high rapport before misinformation increased the amount of accurate information reported in a subsequent witness interview compared to low rapport. However, these recall benefits were not due to a reduction in anxiety. Theoretical implications and practical recommendations for police interviewing practices are discussed.

Pseudo-tumours of the plasma cell granuloma type are reported in two patients. One was retroperitoneal and the other intraabdominal. Most of the cases of plasma cell granulomas described in the literature have been in the lung (Brunn, 1939; Childress and Adie, 1950; Cotton, 1952; Umiker and Iverson, 1954; Lane, Krohn, Kolozai, and Whitehead, 1955; Liebow and Hubbell, 1956; Titus, Harrison, Clagett, Anderson, and Knaff, 1962; Mason, Keats, and Baker, 1963; Wentworth, Lynch, Fallis, Turner, Lowden, and Conen, 1968; Bahadori and Liebow, 1973). A retroperitoneal site has not to our knowledge been reported previously. The postinflammatory nature of such lesions and the significance of a previous history of abdominal surgery are emphasized. It is important to be aware of such benign lesions which may simulate malignant tumours so that unnecessary radical treatment can be avoided.

In view of the favorable claims of Cook and others, an open trial of chronic dorsal column stimulation was undertaken in 9 patients who had moderately advanced multiple sclerosis (MS) but were still ambulatory. No objective improvement was noted by either author during the postoperative observation period of 6 to 37 months; the occasional subjective improvement was ascribed to placebo effect. This procedure can no longer be recommended for MS patients.