Understanding the Dynamics of Protein Lipoylation in Staphylococcus Aureus

Staphylococcus aureus is a commensal bacterium that also acts as an opportunistic pathogen. The pathogenicity of S. aureus has often been attributed to the wide range of virulence factors that the bacterium produces. While virulence factors do contribute a great deal, there is a growing field of research that aims to investigate the role of metabolism in bacterial virulence. My project focuses on the necessity of a metabolic cofactor, lipoic acid. To ensure sufficient amounts of lipoic acid are available for enzyme activity, S. aureus has evolved two pathways to obtain the important nutrient. The lipoic acid salvage pathway is composed of two lipoic acid ligases, LplA1 and LplA2, that sequester environmental lipoic acid. The de novo biosynthesis pathway allows for the transfer of octanoic acid from an acyl carrier protein to GcvH. The octanoic acid is converted to lipoic acid, and LipL facilitates the transfer to the bacterial metabolic protein. While a significant amount is known about these pathways from recent studies in our lab, some questions remain. So far, the Alonzo lab studied the function of LplA1 and LplA2 in the presence of free lipoic acid. While this is valuable in understanding ligase activity, it does not necessarily model the host environment in which there is limited free lipoic acid. A more prevalent substrate is lipoylpeptides. This led me to ask if LplA1 and LplA2 ligases can use lipoamide as a source of lipoic acid for protein lipoylation. Through biochemical lipoylation assays, we discovered that these enzymes are unable to directly use lipoylated peptides; instead, S. aureus harbors lipoamidase functions that allow for generation of the free acid from its peptide-bound form. My thesis also interrogates the activity of LipL. Previously attempts to purify LipL and study it in a lipoylation assay led to no observable function of the protein, and complementation of a ˆ†lipL strain with lipL did not restore of growth defects. I evaluated the lipL gene sequence and determined that the LipL coding sequence in NCBI yields a truncated non-functional gene. Use of an extended LipL in biochemical assays showed that LipL can utilize free lipoic acid alone or in conjunction with LplA1 to lipoylate a limited range of substrates

Brief report of a tablet-delivered psychosocial intervention for men with advanced prostate cancer: Acceptability and efficacy by race

Black men with advanced prostate cancer who participated in a tablet-delivered stress management intervention had greater decreases in prostate cancer-specific anxiety than white men. Relative to non-Hispanic whites (NHW), black men are disproportionately affected by prostate cancer (PC) incidence, have poorer PC outcomes, and report greater compromises in health-related quality of life. Despite these challenges, black men are underrepresented in psychosocial cancer research, possibly due to limited access to supportive oncology programs. The purpose of this article is to examine the acceptability and efficacy for reducing disease-specific distress of a tablet-delivered psychosocial intervention for older men with advanced PC (APC) and explore differences by race. Men with APC ( N = 192, 37.5% black, age M = 68.84 years) were randomized to 10-week Cognitive Behavioral Stress Management (CBSM) or attention-control Health Promotion (HP), both delivered via tablets. Assessments occurred at baseline in person, weekly during the 10-week program via tablets, and at 6 and 12 months in person. Weekly session evaluations and postprogram exit surveys assessed acceptability. Efficacy was assessed with a measure of PC-anxiety validated with racially diverse PC patients using linear mixed effects modeling. Study retention and group attendance did not differ by race. CBSM and HP were both acceptable among older APC patients. Black men rated both conditions more favorably than NHW men. Men in CBSM (vs. HP) reported greater reductions in PC-anxiety at 6 months (not sustained at 12 months). Black men in CBSM reported greater decreases in PC-anxiety over time compared with all other groups. Tablet-delivered CBSM and HP were acceptable for black and NHW APC patients, although black men rated both conditions more favorably. Black men reported a unique intervention benefit related to reduced disease-specific distress

Prospectively Examining the Effects of a Cancer Diagnosis on Patients, Spouses/Partners, and Their Relationship

Patients and their caregivers commonly report positive psychological change following the diagnosis and treatment of cancer, a phenomenon referred to as perceived growth. However, most studies have examined patient and caregiver growth as separate, parallel processes, without considering their dynamic interplay or the shared interpersonal context. Furthermore, previous research is limited by cross-sectional designs that use retrospective self-report measures to capture perceived change following cancer, rather than prospective designs to capture actual, measured changes in positive traits such as character strengths (i.e., character growth). This chapter discusses the challenges involved in examining post-traumatic growth in cancer patient populations and the advantages of incorporating a dyadic process approach as opposed to solely focusing on individual-level change. A dyadic process approach will permit examination of whether disclosure, support, empathy, and cognitive processing operate as mechanisms of character growth and will discuss the need for longitudinal data to fully examine post-traumatic growth as a dyadic outcome. To further elaborate on this dyadic approach, the authors propose an expanded theoretical model to delineate the intrapersonal and shared dyadic processes that underlie character and couple growth among cancer patients and caregivers

Quality of Life in Patients and Their Spouses and Cohabitating Partners in the Year Following a Cancer Biopsy (the Couples Cope Study): Protocol for a Prospective Observational Study

Background Receiving a diagnosis of cancer is a profound and often very stressful experience. Few studies have prospectively recruited patients prior to receiving a new diagnosis of cancer and included spouses or partners. Objective The aim of the Couples Cope Study is to understand the impact of undergoing a diagnostic biopsy and receiving a new cancer diagnosis on quality of life (QoL) in both patients and their spouses or partners, as well as on the quality of their relationship. This protocol paper describes the study design and assesses the feasibility of recruitment and retention. Methods Study staff reviewed the schedules of collaborating physicians using specific encounter codes to identify patients scheduled for breast or prostate biopsies. Potential participants were prescreened via the electronic health record and sent a recruitment letter at least 2 to 3 weeks prior to their biopsy procedure. Patients subsequently underwent a phone screening to determine eligibility. Patients who enrolled provided study staff with contact information for their spouses or partners. All consent forms were completed online. Surveys were completed online prior to receiving the biopsy results (baseline), and at 1, 3, 6, and 9 months after the biopsy. Study staff engaged in ongoing, personalized contact with participants and sent assessment completion reminders via phone and email. Results A total of 2294 patients undergoing a breast or prostate biopsy were identified and 69% (n=1582) were eligible for phone screening following electronic health record prescreening. Of the 431 patients who underwent phone screening, 75% (n=321) were eligible to participate. Of the eligible patients, 72% (n=231) enrolled and 82% (n=190) of enrolled patients had an accompanying partner or spouse who also enrolled. A total of 77% (34/44) of patients who received a cancer diagnosis and 72% (26/36) of their spouses or partners were retained through 9 months, while 80% (53/66) of patients who received a benign diagnosis and 68% (42/62) of their partners were retained. Conclusions Prospective recruitment of patients undergoing diagnostic biopsy and their partners is feasible and requires both strategic collaboration with providers and concerted prescreening and recruitment efforts by study staff. Importantly, this study was able to conduct all study activities online without disrupting clinical workflow and without requiring patients and their spouses or partners to come into the laboratory. Consideration should be given to the ratio of biopsies to cancer diagnoses, which can vary significantly by cancer type. Prospective studies are needed and can inform our ability to provide effective support earlier to couples facing a possible cancer diagnosis. Future studies should examine other tumor types that have received less attention in QoL studies, include behavioral and neurobiological assessments beyond self-report measures, and follow couples beyond 9 months in order to examine long-term effects on QoL. International Registered Report Identifier (IRRID) DERR1-10.2196/5236

Integrating PROMIS® computerized adaptive tests into a web-based intervention for prostate cancer

This study outlined the implementation and feasibility of delivering PROMIS® computer adaptive tests (CATs) using a web-based method to evaluate the impact of a technological adaptation of Cognitive-Behavioral Stress Management (CBSM) on the psychosocial functioning of men with advanced prostate cancer (APC) undergoing hormone therapy. Patients were randomized to a CBSM group intervention (n = 95) or a health promotion (HP) attention-matched control condition (n = 97). Participants attended all sessions via video conference using tablets, and completed PROMIS® computer adaptive tests (CATs) assessing anxiety, depression, fatigue, pain interference, and physical function weekly during the 10-week intervention. Assessment completion rates >50% at week 1 and week 10 demonstrated moderate feasibility of repeatedly administering PROMIS® CATs using a web-based method. Multilevel modeling demonstrated no significant group-by-time interactions from week 1 to week 10 for any of the assessed PROMIS® domains adjusting for sociodemographic and medical covariates. However, simple effects demonstrated decreases in PROMIS® anxiety scores from week 1 to 10 for both groups. Results also demonstrated significant relationships of medical variables to psychosocial functioning across time points. Results highlight the feasibility and benefits of utilizing PROMIS® CATs to repeatedly assess psychosocial functioning using a web-based method and indicate that web-based interventions may be effective for decreasing psychosocial distress and adverse symptoms among men with APC undergoing hormone therapy. (PsycINFO Database Record (c) 2019 APA, all rights reserved)

Symptom burden profiles in men with advanced prostate cancer undergoing androgen deprivation therapy

To identify symptom burden profiles among men with advanced prostate cancer undergoing androgen-deprivation therapy and examine their association with baseline sociodemographic and medical characteristics and psychosocial outcomes over time. Latent profile analysis was employed to identify distinct groups based on the Expanded Prostate Index Composite and the McGill Pain Questionnaire at baseline. Psychosocial outcomes were assessed at baseline, 6- and 12-month follow-ups. Three profiles emerged: “high symptom burden,” “high sexual bother,” and “low symptom burden.” Men with “high symptom burden” were younger and exhibited higher baseline levels of depression, stress, cancer-specific distress, and anxiety than men in the other two groups. However, men with “high symptom burden” also demonstrated improvement in these psychosocial outcomes over time. Men with advanced prostate cancer who experience multiple co-occurring symptoms demonstrate worse psychosocial adjustment. Patients with substantial symptom burden, and specifically young men, may benefit from prompt referral to supportive care services.Division of Cancer Prevention, National Cancer Institute12 month embargo; published: 02 February 2022This item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]

Effects of web-based cognitive behavioral stress management and health promotion interventions on neuroendocrine and inflammatory markers in men with advanced prostate cancer: A randomized controlled trial

•Inflammatory markers decreased among men in stress management and health promotion.•Decreases in inflammatory markers were not sustained at 12 months.•More research is needed to determine whether these interventions impact biomarkers. Cognitive behavioral stress management (CBSM) improves quality of life and mitigates stress biology in patients with early-stage cancer, including men with localized prostate cancer. However, treatments for advanced prostate cancer like androgen deprivation therapy (ADT) can lead to significant symptom burden that may be further exacerbated by stress-induced inflammation and cortisol dysregulation. The aim of this study was to examine the effects of CBSM (versus an active health promotion control) on circulating inflammatory markers and cortisol in men with advanced prostate cancer. Methods: Men with stage III or IV prostate cancer (N = 192) who had undergone ADT within the last year were randomized to CBSM or health promotion. Both interventions were 10 weeks, group-based, and delivered online. Venous blood was drawn at baseline, 6 months, and 12 months to measure circulating levels of CRP, IL-6, IL-8, IL-10, and TNF-α. Saliva samples were collected at awakening, 30 min after awakening, evening, and night for two consecutive days at baseline, 6-months, and 12-months to measure diurnal cortisol slopes. Results: Mixed modeling analyses demonstrated that changes in inflammatory markers and cortisol did not differ by intervention. Men in both CBSM and health promotion showed decreases in IL-10, IL-8, and TNF-α from baseline to 6 months (β = −3.85–−5.04, p’s = 0.004–<0.001). However, these markers generally demonstrated a rebound increase from 6 to 12 months (β = 1.91–4.06, p’s = 0.06–<0.001). Men in health promotion also demonstrated a flatter diurnal cortisol slope versus men in CBSM at 6 months (β = −2.27, p = .023), but not at 12 months. There were no intervention effects on CRP, IL-6, or overall cortisol output. Conclusions: Contrary to hypotheses, CBSM did not lead to changes in the circulating inflammatory markers and cortisol relative to health promotion. CBSM may be associated with healthy diurnal cortisol rhythm because of its focus on cognitive behavioral approaches to stress management. More research is needed to understand the impact of CBSM and health promotion on biomarkers among men with advanced prostate cancer

Technology-Based Psychosocial Intervention to Improve Quality of Life and Reduce Symptom Burden in Men with Advanced Prostate Cancer: Results from a Randomized Controlled Trial

Men with advanced prostate cancer (APC) face multiple challenges including poor prognosis, poor health-related quality of life (HRQOL), and elevated symptom burden. This study sought to establish the efficacy of a tablet-delivered, group-based psychosocial intervention for improving HRQOL and reducing symptom burden in men with APC. We hypothesized that men randomized to cognitive-behavioral stress management (CBSM) would report improved HRQOL and reduced symptom burden relative to men randomized to an active control health promotion (HP) condition. Condition effects on intervention targets and moderators of these effects were explored.Men with APC (N = 192) were randomized (1:1) to 10-week tablet-delivered CBSM or HP, and followed for 1 year. Multilevel modeling was used to evaluate condition effects over time.Changes in HRQOL and symptom burden did not differ between groups. Men in both groups improved across several intervention targets; men in the CBSM condition reported greater increases in self-reported ability to relax, and both conditions showed improvements in cancer-related anxiety, cancer-related distress, and feelings of cohesiveness with other patients over time. Moderating factors included baseline interpersonal disruption, fatigue, and sexual functioning.Tablet-delivered CBSM and HP were well received by men with APC. The hypothesized effects of CBSM on HRQOL and symptom burden were not supported, though improvements in intervention targets were observed across conditions. Participants reported high-baseline HRQOL relative to cancer and general population norms, possibly limiting intervention effects. The identified moderating factors should be considered in the development and implementation of interventions targeting HRQOL and symptom burden.ClinicalTrials.gov Identifier: NCT03149185