Kinetics and Inhibition Studies of the L205R Mutant of cAMP-Dependent Protein Kinase Involved in Cushing’s Syndrome

Overproduction of cortisol by the hypothalamus–pituitary–adrenal hormone system results in the clinical disorder known as Cushing\u27s syndrome. Genomics studies have identified a key mutation (L205R) in the α‐isoform of the catalytic subunit of cAMP‐dependent protein kinase (PKACα) in adrenal adenomas of patients with adrenocorticotropic hormone‐independent Cushing\u27s syndrome. Here, we conducted kinetics and inhibition studies on the L205R‐PKACα mutant. We have found that the L205R mutation affects the kinetics of both Kemptide and ATP as substrates, decreasing the catalytic efficiency (kcat/KM) for each substrate by 12‐fold and 4.5‐fold, respectively. We have also determined the IC50 and Ki for the peptide substrate‐competitive inhibitor PKI(5–24) and the ATP‐competitive inhibitor H89. The L205R mutation had no effect on the potency of H89, but causes a \u3e 250‐fold loss in potency for PKI(5–24). Collectively, these data provide insights for the development of L205R‐PKACα inhibitors as potential therapeutics

Cognitive Behavioural Therapy for schizophrenia - outcomes for functioning, distress and quality of life : A meta-analysis

Background: The effect of cognitive behavioural therapy for psychosis (CBTp) on the core symptoms of schizophrenia has proven contentious, with current meta-analyses finding at most only small effects. However, it has been suggested that the effects of CBTp in areas other than psychotic symptoms are at least as important and potentially benefit from the intervention. Method: We meta-analysed RCTs investigating the effectiveness of CBTp for functioning, distress and quality of life in individuals diagnosed with schizophrenia and related disorders. Data from 36 randomised controlled trials (RCTs) met our inclusion criteria- 27 assessing functioning (1579 participants); 8 for distress (465 participants); and 10 for quality of life (592 participants). Results: The pooled effect size for functioning was small but significant for the end-of-trial (0.25: 95% CI: 0.14 to 0.33); however, this became non-significant at follow-up (0.10 [95%CI -0.07 to 0.26]). Although a small benefit of CBT was evident for reducing distress (0.37: 95%CI 0.05 to 0.69), this became nonsignificant when adjusted for possible publication bias (0.18: 95%CI -0.12 to 0.48). Finally, CBTp showed no benefit for improving quality of life (0.04: 95% CI: -0.12 to 0.19). Conclusions: CBTp has a small therapeutic effect on functioning at end-of-trial, although this benefit is not evident at follow-up. Although CBTp produced a small benefit on distress, this was subject to possible publication bias and became nonsignificant when adjusted. We found no evidence that CBTp increases quality of life post-intervention.Peer reviewedFinal Published versio

All Access: A Backstage Pass to a Collaborative, Undergraduate Music Journal

The number of currently publishing, student run music journals can be counted on one hand. And of those, only half are for undergraduates. At University of the Pacific, the Conservatory of Music started a music industry analysis and opinion journal in 2018. Edited and written by undergraduate students, Backstage Pass has published two issues totaling 47 papers. The benefits of journal writing, editing, publishing and hosting are numerous from many different stakeholder points of view. The collaborative effort is shared between the University Libraries (hosts the institutional repository where the journal is published and offers technical support) and the Conservatory of Music’s Department of Music Industry Studies where the Program Director serves as the Editor-in-Chief and the student editorial board consists of three undergraduates. Backstage Pass serves as a platform to share stellar work being produced at University of the Pacific – potentially attracting new students and celebrating our current students. It allows the students to publish prior to graduating and joining their chosen profession – a profession which, overwhelmingly, requires excellent writing and communication skills. In this presentation, the Editor-in-Chief, one of the student editors, and the Library’s Head of Publishing and Scholarship Support, will discuss the genesis of the journal, the process of publishing the first two issues, and future plans

Greater functional aerobic capacity predicts more effective pain modulation in older adults

poster abstractEndogenous pain inhibitory and facilitory function deteriorates with age, potentially placing older adults at greater risk for chronic pain. Prior research shows that self-reported physical activity predicts endogenous pain inhibitory capacity and facilitation of pain on quantitative sensory tests (QST) in healthy adults. Purpose: To investigate whether functional aerobic capacity and lower extremity strength in older adults cross-sectionally predicts pain sensitivity, pain inhibition following isometric exercise, and facilitation of pain during heat pain temporal summation (TS) tests. Methods: 42 subjects (10 male, 32 female, age=67.5±5.1) completed the 6-minute walk test (6MWT), 30-second chair stand test, and several QSTs. QSTs included: 1) Pain ratings (0-100 scale) during the submersion of the hand in a cold water bath (CWB), 2) heat pain threshold tests, 3) the amount of pain reduction following submaximal isometric exercise, and 4) degree of pain facilitation during temporal summation tests conducted at 44, 46, and 48°C. Responses on the QSTs were analyzed using hierarchical linear regression with meters on 6MWT and number of chair stands as final predictors. Results: After controlling for demographic and psychological factors, aerobic capacity on 6MWT significantly predicted CWB pain ratings (R2 change= 22.5%, Beta= -0.491), pain facilitation during TS trials at 44°C (R2 change= 16.7%, Beta= -0.446), and the amount of pain reduction following isometric exercise (R2 change= 20.7%, Beta= 0.393). All other analyses were not significant (P>0.05). Conclusions: Older adults exhibiting greater functional aerobic capacity displayed reduced cold pain sensitivity, reduced pain facilitory function, and increased pain inhibition following exercise. These findings suggest that increased aerobic fitness in older adults may be associated with more effective endogenous modulation of pain. This study was funded by the IUPUI School of PETM Faculty Research Opportunity Grant

Weight loss attitudes and social forces in urban poor Black and White women

OBJECTIVE: To explore differences between Blacks and Whites in perceived influences on weight-related behaviors among obese urban poor women. METHODS: Participants (N = 27) received physician referrals to a weight loss program located in Federally Qualified Health Centers and either never attended or stopped attending. We conducted in-depth, in home interviews using a script informed by focus groups, pilot discussions, and the theory of planned behavior (TPB) to learn about participants' weight loss attitudes, social forces and perceived behavioral control. RESULTS: White women reported having more social support and social pressure for weight management activities. Black women reported eating for positive reasons whereas white women associated eating with negative emotions. CONCLUSION: Social networks and emotions may be critical factors in weight management and lifestyle program participation

Outcomes of an RCT of video‐conference vs. in‐person or in‐clinic nutrition and exercise in midlife adults with obesity

Objective New communication technologies have shown some promise in lifestyle weight loss interventions, but may be most effective when leveraging face‐to‐face communications. The study reported here sought to test whether weight loss program attendance and outcomes are greater when offered in‐person at community sites or remotely via videoconference versus in federally qualified health centers (FHQCs). In a three‐arm randomized trial among 150 FQHC adults, intervention delivery in community‐sites or via videoconference were tested against a clinic‐based lifestyle intervention (enhanced usual care [EUC]). Methods Twice weekly, a nutrition topic was reviewed, and exercise sessions were held in a 20‐week program delivered either in community settings or via videoconference. The primary outcome was the proportion of participants losing more than 2 kg at 6 (end of treatment) and 12 months in intent‐to‐treat analyses. Results Mean (SD) age was 53 (7) years, 82% were female, 65% were African‐American, 50% reported $18,000 or less household income, 49% tested low in health literacy, and mean (SD) body mass index was 39 (6) kg/m2. The proportion losing more than 2 kg of weight in the community site, videoconference, and EUC groups was 33%, 34%, and 24%, respectively at 6 months, and 29%, 34%, and 29% at 12 months. No differences reached significance. Attendance was poor in all groups; 45% of community site, 58% of videoconference, and 16% of EUC participants attended at least one session. Conclusion Videoconference and community‐based delivery were as effective as an FQHC‐based weight loss program

Manipulating target size influences perceptions of success when learning a dart-throwing skill but does not impact retention

Positive feedback or experiences of success during skill acquisition have been shown to benefit motor skill learning. In this study, our aim was to manipulate learners’ success perceptions through a minor adjustment to goal criterion (target size) in a dart-throwing task. Two groups of novice participants practiced throwing at a large (easy) or a small (difficult) target from the same distance. In reference to the origin/centre of the target, the practice targets were alike in objective difficulty and indeed participants in both groups were not different in their objective practice performance (i.e. radial error from the centre). Although the groups experienced markedly different success rates, with the large target group experiencing more hits and reporting greater confidence (or self-efficacy) than the small target group, these practice effects were not carried into longer-term retention, which was assessed after a one-week delay. For success perceptions to moderate or benefit motor learning, we argue that unambiguous indicators of positive performance are necessary, especially for tasks where intrinsic feedback about objective error is salient

Racial Stratification in Self-Rated Health Among Black Mexicans and White Mexicans

How do Mexicans of distinct racial backgrounds fit into the recognized patterns of racial health disparities? We conduct regression analyses using data from the 2000-2017 National Health Interview Survey to determine if Mexicans who self-identify as White or Black have a relative advantage or disadvantage in self-rated health in relation to Non-Hispanic (NH) Whites and Blacks in the U.S. Our results indicate that both Black Mexicans and White Mexicans have a significant disadvantage in relation to NH-Whites while White Mexicans have a slight advantage in relation to both NH-Blacks and Black Mexicans. Overall, our results suggest that studying health outcomes among Hispanics without considering race may mask inequalities not observed in the aggregate

Analysis of Storage Methods and Tarping Practices for Corn Stover Bales

In 2011 and 2012, Iowa State University conducted storage trials for large, rectangular corn stover bales to determine the most effective storage method for companies and farmers harvesting corn stover. Over 2000 bales were used for different storage trials, and five storage configurations were tested. Standard outdoor tarped and indoor stacks proved to be the most effective in preserving bale quality and limiting deterioration, with dry matter losses below 5% in 2012. Moisture content of the bales was studied by collecting pre and post-storage moisture contents of the bales. It was found that all bales, no matter the initial moisture content, would dry down to an industrial-acceptable moisture content of nearly 15%, if stored appropriately. Bale temperatures, which are an indicator of moisture content and microbial activity, were also studied to support the dry matter loss and moisture content data, as well as to ensure these stacks were not creating opportunities for bales to self-combust. In both years of temperature studies, no bales were found to reach temperatures near self-combustion level