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.

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.

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 (ß = -3.85--5.04, p's = 0.004-<0.001). However, these markers generally demonstrated a rebound increase from 6 to 12 months (ß = 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 (ß = -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.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03149185.

Dynamic Relay of Protein-Bound Lipoic Acid in Staphylococcus aureus.

Staphylococcus aureus competes for myriad essential nutrients during host infection. One of these nutrients is the organosulfur compound lipoic acid, a cofactor required for the activity of several metabolic enzyme complexes. In S. aureus, these include the E2 subunits of three α-ketoacid dehydrogenases and two H proteins, GcvH of the glycine cleavage system and its paralog, GcvH-L. We previously determined that the S. aureus amidotransferase LipL is required for lipoylation of the E2 subunits of pyruvate dehydrogenase (PDH) and branched-chain 2-oxoacid dehydrogenase (BCODH) complexes. The results from this study, coupled with those from Bacillus subtilis, suggested that LipL catalyzes lipoyl transfer from H proteins to E2 subunits. However, to date, the range of LipL targets, the extent of LipL-dependent lipoic acid shuttling between lipoyl domain-containing proteins, and the importance of lipoyl relay in pathogenesis remain unknown. Here, we demonstrate that LipL uses both lipoyl-H proteins as the substrates for lipoyl transfer to all E2 subunits. Moreover, LipL facilitates lipoyl relay between E2 subunits and between H proteins, a property that potentially constitutes an adaptive response to nutrient scarcity in the host, as LipL is required for virulence during infection. Together, these observations support a role for LipL in facilitating flexible lipoyl relay between proteins and highlight the complexity of protein lipoylation in S. aureusIMPORTANCE Protein lipoylation is a posttranslational modification that is evolutionarily conserved from bacteria to humans. Lipoic acid modifications are found on five proteins in S. aureus, four of which are components of major metabolic enzymes. In some bacteria, the amidotransferase LipL is critical for the attachment of lipoic acid to these proteins, and yet it is unclear to what extent LipL facilitates the transfer of this cofactor. We find that S. aureus LipL flexibly shuttles lipoic acid among metabolic enzyme subunits, alluding to a dynamic redistribution mechanism within the bacterial cell. This discovery exemplifies a potential means by which bacteria optimize the use of scarce nutrients when resources are limited.

Increased flexibility in the use of exogenous lipoic acid by Staphylococcus aureus.

Lipoic acid is a cofactor required for intermediary metabolism that is either synthesized de novo or acquired from environmental sources. The bacterial pathogen Staphylococcus aureus encodes enzymes required for de novo biosynthesis, but also encodes two ligases, LplA1 and LplA2, that are sufficient for lipoic acid salvage during infection. S. aureus also encodes two H proteins, GcvH of the glycine cleavage system and the homologous GcvH-L encoded in an operon with LplA2. GcvH is a recognized conduit for lipoyl transfer to α-ketoacid dehydrogenase E2 subunits, while the function of GcvH-L remains unclear. The potential to produce two ligases and two H proteins is an unusual characteristic of S. aureus that is unlike most other Gram positive Firmicutes and might allude to an expanded pathway of lipoic acid acquisition in this microorganism. Here, we demonstrate that LplA1 and LplA2 facilitate lipoic acid salvage by differentially targeting lipoyl domain-containing proteins; LplA1 targets H proteins and LplA2 targets α-ketoacid dehydrogenase E2 subunits. Furthermore, GcvH and GcvH-L both facilitate lipoyl relay to E2 subunits. Altogether, these studies identify an expanded mode of lipoic acid salvage used by S. aureus and more broadly underscore the importance of bacterial adaptations when faced with nutritional limitation.

Prolapse repair with and without apical resuspension-Practice patterns among certifying American urologists.

AIMS: To examine surgeon characteristics in certifying urologists performing prolapse surgeries. Anterior compartment prolapse is often associated with apical prolapse, with high rates of recurrence when anterior repair is performed without apical resuspension. METHODS: Six-month case log data of certifying urologists between 2003 and 2013 was obtained from the American Board of Urology (ABU). Cases with a CPT code for common prolapse repairs in females ≥18 years were analyzed. RESULTS: Among 2,588 urologists logging at least one prolapse surgery and a total of 30,983 surgeries, 320 (1.0% of all cases) uterosacral ligament suspension, 3,673 (11.9%) sacrospinous ligament suspension, and 2,618 (8.4%) abdominal sacrocolpopexy were identified. The remaining 14,585 cases were logged as anterior repair. 54.7% of anterior repairs did not include apical suspension. The proportion of anterior repairs without apical suspension has decreased from 77.7% in 2004 to 41.4% in 2012 (P < 0.001). Female subspecialists before 2011 performed anterior repair without apical suspension in 58.5%, versus 70.3% by all others. Since 2011 there has been a decrease in number of anterior repairs without apical suspension, notably in those applying for Female Pelvic Medicine and Reconstructive Surgery (FPMRS) certification (17.1% vs. 30.7% by all other urologists, P < 0.001); nonacademically affiliated urologists are 2.1 times more likely to report anterior repair without apical suspension than academically affiliated colleagues (P < 0.001). CONCLUSIONS: The proportion of prolapse repairs reported as anterior repairs without apical suspension is decreasing, although it remains a substantial portion. Recent log year, FPMRS, and academic affiliation were associated with prolapse repairs addressing apical support. Neurourol. Urodynam. 36:344-348, 2017. © 2015 Wiley Periodicals, Inc.

Disparities in female urologic case distribution with new subspecialty certification and surgeon gender.

AIMS: To examine surgical case volume characteristics in certifying urologists associated with common female urologic procedures to evaluate the practice patterns, given the recent establishment of subspecialty certification in Female Pelvic Medicine and Reconstructive Surgery (FPMRS) and changes in urologist gender composition. METHODS: Six-month case log data of certifying urologists (2003-2013) was obtained from the American Board of Urology (ABU). We examined case logs for 26 CPT codes for common female urologic procedures focused on four procedure groups: incontinence, prolapse, vesicovaginal fistula (VVF), and revision/removal of vaginal mesh/graft. RESULTS: Among 4802 urologists logging at least one female urology case, 43,949 (55.6% of all cases) incontinence, 30,983 (39.2%) prolapse, 451 (0.6%) VVF, and 3643 (4.6%) revision of mesh/graft surgeries were identified. While 90.8% logging at least one female CPT code were men, women surgeons (9.2%) accounted for a disproportionate volume (22.6%) of cases. With initiation of the FPMRS subspecialty certification in 2011, 225 FPMRS candidates (out of 1716 certifying urologists) were identified, compared to 367 (out of 3828 certifying urologists) female subspecialists prior to 2011. FPMRS accounted for 56.7% of prolapse, 62.9% VVF, 59.0% mesh/graft revisions, and 41.9% of incontinence surgeries, compared to female specialists before 2011 (39.1%, 42.4%, 41.5%, and 21.6% respectively (all P < 0.001)). CONCLUSIONS: A growing proportion of female urologic cases are performed by female subspecialists, with a significant increase since initiation of FPMRS subspecialty certification. Women surgeons account for a disproportionate volume of these cases despite remaining a minority of certifying urologists and female subspecialists. Neurourol. Urodynam. 36:399-403, 2017. © 2015 Wiley Periodicals, Inc.

Insights into the Function of a Second, Nonclassical Ahp Peroxidase, AhpA, in Oxidative Stress Resistance in Bacillus subtilis.

UNLABELLED: Organisms growing aerobically generate reactive oxygen-containing molecules, such as hydrogen peroxide (H2O2). These reactive oxygen molecules damage enzymes and DNA and may even cause cell death. In response, Bacillus subtilis produces at least nine potential peroxide-scavenging enzymes, two of which appear to be the primary enzymes responsible for detoxifying peroxides during vegetative growth: a catalase (encoded by katA) and an alkylhydroperoxide reductase (Ahp, encoded by ahpC). AhpC uses two redox-active cysteine residues to reduce peroxides to nontoxic molecules. A specialized thioredoxin-like protein, AhpF, is then required to restore oxidized AhpC back to its reduced state. Curiously, B. subtilis has two genes encoding Ahp: ahpC and ahpA. Although AhpC is well characterized, very little is known about AhpA. In fact, numerous bacterial species have multiple ahp genes; however, these additional Ahp proteins are generally uncharacterized. We seek to understand the role of AhpA in the bacterium's defense against toxic peroxide molecules in relation to the roles previously assigned to AhpC and catalase. Our results demonstrate that AhpA has catalytic activity similar to that of the primary enzyme, AhpC. Furthermore, our results suggest that a unique thioredoxin redox protein, AhpT, may reduce AhpA upon its oxidation by peroxides. However, unlike AhpC, which is expressed well during vegetative growth, our results suggest that AhpA is expressed primarily during postexponential growth. IMPORTANCE: B. subtilis appears to produce nine enzymes designed to protect cells against peroxides; two belong to the Ahp class of peroxidases. These studies provide an initial characterization of one of these Ahp homologs and demonstrate that the two Ahp enzymes are not simply replicates of each other, suggesting that they instead are expressed at different times during growth of the cells. These results highlight the need to further study the Ahp homologs to better understand how they differ from one another and to identify their function, if any, in protection against oxidative stress. Through these studies, we may better understand why bacteria have multiple enzymes designed to scavenge peroxides and thus have a more accurate understanding of oxidative stress resistance.

The Gender Divide: The Impact of Surgeon Gender on Surgical Practice Patterns in Urology.

PURPOSE: There is a perception in urology that female urologists encounter gender based role assignments and are often pigeonholed into caring for more female patients and female specific urological issues than their male colleagues. We assessed the influence of surgeon gender on patient gender demographics by exploring the surgical case logs of American urologists. MATERIALS AND METHODS: Six-month case logs of certifying urologists from 2003 to 2012 were obtained from the ABU (American Board of Urology). We reviewed case logs based on CPT codes of common urological procedures, focusing on 6 index gender neutral and gender specific procedure groups, including treatment of nephrolithiasis, nephrectomy, resection of bladder tumors, treatment of stress urinary incontinence, elective sterilization and treatment of prostate cancer. RESULTS: Among a cohort of 6,166 urologists 1,011,800 cases were logged. Female surgeons operated on a significantly higher percent of female patients than their male peers (54.4% vs 32.5%, p <0.01). Female surgeons performed significantly more female specific procedures, such as slings, than their male counterparts (18 vs 10 per year, p <0.001). Male urologists performed significantly more male specific procedures than their female colleagues, including 3 times as many vasectomies (32 vs 12 per year, p <0.001) and more than twice as many prostatectomies (15 vs 6 per year, p <0.001). These trends were consistent across all subspecialties and geographic regions (p <0.01). CONCLUSIONS: Female surgeon gender has a significant influence on patient gender demographics among index urological procedures. As the number of women in urology grows, increasing attention to gender biases is necessary to understand how these disparities will shape the clinical landscape.

Feasibility, acceptability, and preliminary efficacy of a technology-assisted psychosocial intervention for racially diverse men with advanced prostate cancer.

BACKGROUND: The utility of psychosocial interventions in reducing symptom burden and improving health-related quality of life (HRQOL) for men with localized prostate cancer has been demonstrated. However, studies have yet to demonstrate the efficacy of interventions in advanced prostate cancer (APC). This study examined the feasibility, acceptability, and preliminary efficacy of a technology-assisted, 10-week, group-based psychosocial intervention for diverse men with APC. METHODS: The participants were 74 men (mean age, 68.84 years; non-Hispanic white, 57%; black, 40.5%) who were randomized to a cognitive-behavioral stress management (CBSM) treatment or health promotion (HP) attention-control condition. The participants were assessed at the baseline, weekly throughout the 10-week program, and 6 months after the baseline. Outcomes were assessed with the Patient-Reported Outcomes Measurement Information System along with established measures of HRQOL, CBSM intervention targets (eg, relaxation skills), and patient-reported acceptability. RESULTS: Feasibility was demonstrated through good retention rates (>85%) and acceptable average attendance rates (>70%), and acceptability was demonstrated through very favorable weekly session evaluations (mean score, 4/5) and exit surveys (mean score, 3.6/4). Men randomized to the CBSM condition reported significant reductions (P < .05) in depressive symptoms and improvements in relaxation self-efficacy (P < .05) at the 6-month follow-up. CBSM participants reported trends for improvement in distress and functional well-being (P < .08) in comparison with those in the HP condition. Effect sizes ranged from medium (0.54) to large (1.87) and, in some instances, were clinically meaningful. CONCLUSIONS: Technology-based CBSM interventions among diverse men with APC may be feasible, acceptable, and efficacious.

National practice patterns of treatment of erectile dysfunction with penile prosthesis implantation.

PURPOSE: The increase in medical options to manage erectile dysfunction has changed how urologists approach erectile dysfunction. We reviewed contemporary trends in penile prosthesis implantation in the United States with an emphasis on practice patterns, demographics and temporal changes. MATERIALS AND METHODS: Annualized case log data of penile prosthesis surgeries from certifying and recertifying urologists from 2003 to 2012 were obtained from the American Board of Urology. CPT code 54400 was used to identify malleable prosthesis surgeries and CPT codes 54401 and 54405 were used to identify inflatable prosthesis surgeries. To evaluate the association between surgeon characteristics and practice patterns we used the chi-square test. RESULTS: The surgical cohort included 6,615 urologists who placed a total of 9,558 penile prostheses during the study period. Only 23.9% of urologists reported performing a penile prosthesis operation. Of the prostheses 75% were placed by surgeons who completed 4 or fewer such operations per year. Of urologists who recorded logs 1.5% considered themselves to be specialists in andrology and yet they were responsible for a disproportionate 10% of all prostheses implanted (OR 5.9, p <0.0001). The proportion of inflatable penile prostheses compared to malleable prostheses increased twelvefold in 10 years. The number of logged prosthesis surgeries was skewed toward more implants placed by the most experienced urologists than by new urologists (OR 1.92, p <0.0001). CONCLUSIONS: Although specialists and high volume surgeons perform a disproportionate number of implant surgeries, low volume surgeons place most penile prostheses in the United States. Additional research is needed to determine best practices to achieve optimal patient outcomes in penile prosthesis surgery.

Contemporary surgical trends in the management of upper tract calculi.

PURPOSE: Upper tract nephrolithiasis is a common surgical condition that is treated with multiple surgical techniques, including shock wave lithotripsy, ureteroscopy and percutaneous nephrolithotomy. We analyzed case logs submitted to the ABU by candidates for initial certification and recertification to help elucidate the trends in management of upper tract urinary calculi. MATERIALS AND METHODS: Annualized case logs from 2003 to 2012 were analyzed. We used logistic regression models to assess how surgeon specific attributes affected the way that upper tract stones were treated. Cases were identified by the CPT code of the corresponding procedure. RESULTS: A total of 6,620 urologists in 3 certification groups recorded case logs, including 2,275 for initial certification, 2,381 for first recertification and 1,964 for second recertification. A total of 441,162 procedures were logged, of which 54.2% were ureteroscopy, 41.3% were shock wave lithotripsy and 4.5% were percutaneous nephrolithotomy. From 2003 to 2013 there was an increase in ureteroscopy from 40.9% to 59.6% and a corresponding decrease in shock wave lithotripsy from 54% to 36.3%. For new urologists ureteroscopy increased from 47.6% to 70.9% of all stones cases logged and for senior clinicians ureteroscopy increased from 40% to 55%. Endourologists performed a significantly higher proportion of percutaneous nephrolithotomies than nonendourologists (10.6% vs 3.69%, p <0.0001) and a significantly smaller proportion of shock wave lithotripsies (34.2% vs 42.2%, p = 0.001). CONCLUSIONS: Junior and senior clinicians showed a dramatic adoption of endoscopic techniques. Treatment of upper tract calculi is an evolving field and provider specific attributes affect how these stones are treated.

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): DERR1-10.2196/52361.

Age and 17ß-Estradiol (E2) Facilitate Nuclear Export and Argonaute Loading of microRNAs in the Female Brain.

Aging in women is accompanied by a dramatic change in circulating sex steroid hormones. Specifically, the primary circulating estrogen, 17ß-estradiol (E2), is nearly undetectable in post-menopausal women. This decline is associated with a variety of cognitive and mood disorders, yet hormone replacement therapy is only effective within a narrow window of time surrounding the menopausal transition. Our previous work identified microRNAs as a potential molecular substrate underlying the change in E2 efficacy associated with menopause in advanced age. Specifically, we showed that E2 regulated a small subset of mature miRNAs in the aging female brain. In this study, we hypothesized that E2 regulates the stability of mature miRNAs by altering their subcellular localization and their association with argonaute proteins. We also tested the hypothesis that the RNA binding protein, hnRNP A1, was an important regulator of mature miR-9-5p expression in neuronal cells. Our results demonstrated that E2 treatment affected miRNA subcellular localization and its association with argonaute proteins differently, depending on the length of time following E2 deprivation (i.e., ovariectomy). We also provide strong evidence that hnRNP A1 regulates the transcription of pri-miR-9 and likely plays a posttranscriptional role in mature miR-9-5p turnover. Taken together, these data have important implications for considering the optimal timing for hormone replacement therapy, which might be less dependent on age and more related to how long treatment is delayed following menopause.

Absolute Quantification of Phosphorylated ERß Amino Acids in the Hippocampus of Women and in A Rat Model of Menopause.

The rapid decline of circulating 17ß-estradiol (E2) at menopause leads to negative neurological consequences, although hormone therapy paradoxically has both harmful and positive effects depending on the age at which it is delivered. The inconsistent response to E2 suggests unappreciated regulatory mechanisms for estrogen receptors (ERs), and we predicted it could be due to age-related differences in ERß phosphorylation. We assessed ERß phosphorylation using a sensitive mass spectrometry approach that provides absolute quantification (AQUA-MS) of individually phosphorylated residues. Specifically, we quantified phosphorylated ERß in the hippocampus of women (aged 21-83 years) and in a rat model of menopause at 4 residues with conserved sequence homology between the 2 species: S105, S176, S200, and Y488. Phosphorylation at these sites, which spanned all domains of ERß, were remarkably consistent between the 2 species, showing high levels of S105 phosphorylation (80%-100%) and low levels of S200 (20%-40%). Further, S200 phosphorylation decreased with aging in humans and loss of E2 in rats. Surprisingly, Y488 phosphorylation, which has been linked to ERß ligand-independent actions, exhibited approximately 70% phosphorylation, unaltered by species, age, or E2, suggesting ERß's primary mode of action may not require E2 binding. We further show phosphorylation at 2 sites directly altered ERß DNA-binding efficiency, and thus could affect its transcription factor activity. These findings provide the first absolute quantification of ERß phosphorylation in the human and rat brain, novel insights into ERß regulation, and a critical foundation for providing more targeted therapeutic options for menopause in the future.

17ß-Estradiol Regulates miR-9-5p and miR-9-3p Stability and Function in the Aged Female Rat Brain.

Clinical studies demonstrated that the ovarian hormone 17ß-estradiol (E2) is neuroprotective within a narrow window of time following menopause, suggesting that there is a biological switch in E2 action that is temporally dependent. However, the molecular mechanisms mediating this temporal switch have not been determined. Our previous studies focused on microRNAs (miRNA) as one potential molecular mediator and showed that E2 differentially regulated a subset of mature miRNAs which was dependent on age and the length of time following E2 deprivation. Notably, E2 significantly increased both strands of the miR-9 duplex (miR-9-5p and miR-9-3p) in the hypothalamus, raising the possibility that E2 could regulate miRNA stability/degradation. We tested this hypothesis using a biochemical approach to measure miRNA decay in a hypothalamic neuronal cell line and in hypothalamic brain tissue from a rat model of surgical menopause. Notably, we found that E2 treatment stabilized both miRNAs in neuronal cells and in the rat hypothalamus. We also used polysome profiling as a proxy for miR-9-5p and miR-9-3p function and found that E2 was able to shift polysome loading of the miRNAs, which repressed the translation of a predicted miR-9-3p target. Moreover, miR-9-5p and miR-9-3p transcripts appeared to occupy different fractions of the polysome profile, indicating differential subcellular. localization. Together, these studies reveal a novel role for E2 in modulating mature miRNA behavior, independent of its effects at regulating the primary and/or precursor form of miRNAs.

Reentry of endodontic access cavities: composite residue and loss of tooth substance.

The purpose of this study was to investigate the ability of dentists to remove composite fillings from endodontic access cavities using illumination from a conventional light source (CLS) versus the fluorescence-aided identification technique (FIT) in terms of completeness, selectivity and treatment duration. Therefore, two independent operators removed composite resin from six sets of root-filled incisors in a maxillary model under simulated clinical conditions using the CLS or FIT method (twelve teeth per operator and technique). The duration of treatment was recorded and before-after micro-CT scans were superimposed for volumetric assessment of treatment completeness and selectivity. Statistical significance was determined by t-testing and two-way ANOVA for operator comparison. Overall, there was no significant difference between FIT and CLS in terms of volume, height and area of composite residues (p=0.98 / p=0.75 / p=0.64) and regarding hard tissue loss in terms of volume, depth and area (p= 0.93 / p= 0.70 / p= 0.14). However, there was a significant difference between the two groups regarding treatment time (FIT= 428s, CLS=523s; p=0.023). Significant differences between operators regardless of method were found for volume, height and area of composite residues (p<0.05) and also for defect area (p=0.01) and time (p<0.001). Significant differences between operators including the method was only found for height of composites (p=0.037). It can be concluded, that composite remnants and tooth structure losses may occur after reentry of root-filled teeth regardless of the illumination method (conventional vs. fluorescence-aided) and operator, but preparation was less time-consuming with FIT.

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

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.

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

OBJECTIVE: 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. METHOD: 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. RESULTS: 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. CONCLUSIONS: 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).

Auditory hallucinations in adolescent and adult students: implications for continuums and adult pathology following child abuse.

An auditory hallucination questionnaire was completed by 250 adolescents and 250 adults in the UK to provide data concerning their hallucinatory experiences, which enabled a consideration of nonclinical population auditory hallucination experiences. The data gathered from the adolescent group were almost identical to that of the adult group, suggesting a continuum between child and adulthood. The data also indicated that the UK adult sample was very similar to an established US sample of adults. The current data was combined with previously published data to construct a proposed developmental model that may link child abuse to pathological hallucinations and possible later mental illness issues. New normative data concerning hallucinatory experiences provide important norms, which need to be considered for adolescents or young adults who may be considered for early intervention in psychosis programs. These new norms provide information that should be considered in a variety of therapeutic settings.