Cognition, Coping, and Psychological Distress in HIV.

Interrelationships among HIV-associated neurocognitive dysfunction, avoidant coping, cognitively-oriented coping, and psychological distress were examined using structural equation modeling in an ethnically diverse sample of 209 adults predominantly in the mid-range of illness. Global neurocognitive deficits, assessed with the HIV-dementia scale, were associated with higher levels of avoidant coping, lower levels of cognitive coping, and a higher avoidant/cognitive coping ratio, which were each in turn associated with higher psychological distress measured by a latent factor comprising symptoms of depression, anxiety, and HIV-related distressing thoughts. There were significant indirect effects through avoidant coping and a higher avoidant/cognitive coping ratio. Results suggest the presence of HIV-associated neurocognitive deficits may interfere with the utilization of cognitive-based coping strategies and increase reliance on  more maladaptive strategies, which in turn may translate to elevated reports of  psychological distress. Findings may help inform interventions aimed at reducing avoidant coping and psychological distress, two factors associated with accelerated HIV disease progression.

Structural Basal Ganglia Correlates of Subjective Fatigue in Middle-Aged and Older Adults.

OBJECTIVE: Fatigue is among the most common complaints in community-dwelling older adults, yet its etiology is poorly understood. Based on models implicating frontostriatal pathways in fatigue pathogenesis, we hypothesized that smaller basal ganglia volume would be associated with higher levels of subjective fatigue and reduced set-shifting in middle-aged and older adults without dementia or other neurologic conditions. METHODS: Forty-eight non-demented middle-aged and older adults (Mage = 68.1, SD = 9.4; MMMSE = 27.3, SD = 1.9) completed the Fatigue Symptom Inventory, set-shifting measures, and structural MRI as part of a clinical evaluation for subjective cognitive complaints. Associations were examined cross-sectionally. RESULTS: Linear regression analyses showed that smaller normalized basal ganglia volumes were associated with more severe fatigue (ß = -.29, P = .041) and poorer Trail Making Test B-A (TMT B-A) performance (ß = .30, P = .033) controlling for depression, sleep quality, vascular risk factors, and global cognitive status. Putamen emerged as a key structure linked with both fatigue (r = -.43, P = .003) and TMT B-A (ß = .35, P = .021). The link between total basal ganglia volume and reduced TMT B-A was particularly strong in clinically fatigued patients. CONCLUSION: This study is among the first to show that reduced basal ganglia volume is an important neurostructural correlate of subjective fatigue in physically able middle-aged and older adults without neurological conditions. Findings suggest that fatigue and rapid set-shifting deficits may share common neural underpinnings involving the basal ganglia, and provide a framework for studying the neuropathogenesis and treatment of subjective fatigue.

Impaired Neurocognitive Performance and Mortality in HIV: Assessing the Prognostic Value of the HIV-Dementia Scale.

This study examined whether global HIV-associated neurocognitive impairment (NCI), assessed with the HIV-Dementia Scale (HDS), predicted mortality in an ethnically diverse sample of 209 HIV-positive adults. Participants were predominantly in the mid-range of illness at baseline, and followed over 13-years. At baseline, 31 (15%) participants scored in the NCI range (HDS ≤ 10); 58 (28%) died during follow-up. Baseline NCI was significantly associated with earlier mortality (HR = 2.10, 95% CI [1.10-4.00]) independent of sociodemographic and HIV disease-related covariates. Less errors on the antisaccade task, an index of executive/attention control, was the only HDS subtest predicting earlier mortality (HR = 0.72, 95% CI [0.58-0.90]). In the absence of an AIDS-defining condition, NCI, particularly in the executive/attention domain, is an independent prognostic marker of mortality in a diverse HIV-positive cohort. These findings highlight the clinical utility of brief cognitive screening measures in this population.

Sleep quality mediates the relationship between frailty and cognitive dysfunction in non-demented middle aged to older adults.

ABSTRACTObjectives:Frailty is associated with cognitive decline in older adults. However, the mechanisms explaining this relationship are poorly understood. We hypothesized that sleep quality may mediate the relationship between frailty and cognition. PARTICIPANTS: 154 participants aged between 50-90 years (mean = 69.1 years, SD = 9.2 years) from the McKnight Brain Registry were included. MEASUREMENTS: Participants underwent a full neuropsychological evaluation, frailty and subjective sleep quality assessments. Direct relationships between frailty and cognitive function were assessed using linear regression models. Statistical mediation of these relationships by sleep quality was assessed using nonparametric bootstrapping procedures. RESULTS: Frailty severity predicted weaker executive function (B = -2.77, ß = -0.30, 95% CI = -4.05 - -1.29) and processing speed (B = -1.57, ß = -0.17, 95% CI = -3.10 - -0.16). Poor sleep quality predicted poorer executive function (B = -0.47, ß = -0.21, 95% CI = -0.79 - -0.08), processing speed (B = -0.64, ß = -0.28, 95% CI = -0.98 - -0.31), learning (B = -0.42, ß = -0.19, 95% CI = -0.76 - -0.05) and delayed recall (B = -0.41, ß = -0.16, 95% CI = -0.80 - -0.31). Poor sleep quality mediated the relationships between frailty severity and executive function (B = -0.66, ß = -0.07, 95% CI = -1.48 - -0.39), learning (B = -0.85, ß = -0.07, 95% CI = -1.85 - -0.12), delayed recall (B = -0.47, ß = -0.08, 95% CI = -2.12 - -0.39) and processing speed (B = -0.90, ß = -0.09, 95% CI = -1.85 - -0.20). CONCLUSIONS: Relationships between frailty severity and several cognitive outcomes were significantly mediated by poor sleep quality. Interventions to improve sleep quality may be promising avenues to prevent cognitive decline in frail older adults.

The Indirect Effect of Posttraumatic Stress Disorder Symptoms on Current Alcohol Use Through Negative Cognitions in Sexual Minority Men.

Self-medication theory posits that some trauma survivors use alcohol to cope with posttraumatic stress disorder (PTSD) symptoms, but the role of negative posttraumatic cognitions in this relationship is not well defined. We examined associations among PTSD symptoms, posttraumatic cognitions, and alcohol intoxication frequency in 290 men who have sex with men (MSM), who reported a history of childhood sexual abuse (CSA). Using a bootstrap approach, we examined the indirect effects of PTSD symptoms on alcohol intoxication frequency through posttraumatic cognitions regarding the self, world, and self-blame. In separate regression models, higher levels of PTSD symptoms and posttraumatic cognitions were each associated with more frequent intoxication, accounting for 2.6% and 5.2% of the variance above demographics, respectively. When examined simultaneously, posttraumatic cognitions remained significantly correlated with intoxication frequency whereas PTSD symptoms did not. Men reporting elevated posttraumatic cognitions faced increased odds for current alcohol dependence, odds ratio (OR) = 2.19, 95% CI [1.13, 4.22], compared with men reporting low posttraumatic cognitions, independent of current PTSD diagnosis. A higher level of PTSD symptom severity was indirectly associated with more frequent alcohol intoxication through cognitions about the self and world; the indirect to total effect ratios were 0.74 and 0.35, respectively. Negative posttraumatic cognitions pertaining to individuals' self-perceptions and appraisals of the world as dangerous may play a role in self-medication with alcohol among MSM with a history of CSA. Interventions targeting these cognitions may offer potential for reducing alcohol misuse in this population, with possible broader implications for HIV-infection risk.

Revenue from single-balloon enteroscopy is driven by anesthesia: experience from a tertiary care facility.

BACKGROUND/AIMS: Resource-intensive endoscopic procedures have shown to generate more costs than revenue under the current reimbursement system in the USA. Single-balloon enteroscopy (SBE), a resource-intensive procedure, has never been evaluated for its financial impact at tertiary care hospitals, and thus, our aim was to determine the sources of revenue that SBE procedures generate. METHODS: Retrospective review of all procedures performed using the SBE system during the first year of implementation at a single tertiary referral center. Financial data from two subspecialties in the form of revenues for physician and facility fees were collected and analyzed. Revenues were analyzed in total and as a function of payer (insurance) and physician type. RESULTS: Fifty-two procedures using the SBE system were identified during the first year of implementation at a single tertiary care center. Total revenue generated for all SBE procedures was $123,714 including $64,475 dollars from physician fees and $59,239 dollars from the facility fees. Revenue generated by anesthesia physician fees was higher from Medicare cases compared to private insurance cases (p < 0.01); however, revenues from facility fees were higher for private insurance cases compared to Medicare (p < 0.01). Revenues from anesthesiology physician fees were significantly more than revenues from GI physician fees (p < 0.01). Of the three referred cases, one generated additional downstream revenues from other non-SBE-related services totaling $4727. CONCLUSION: A large proportion of revenues generated from SBE cases come in the form of ancillary services provided by anesthesia. Projected revenue generation (and it sources) should be considered when establishing a device-assisted enteroscopy program.

WLS-dependent secretion of WNT3A requires Ser209 acylation and vacuolar acidification.

Wnt proteins are secreted post-translationally modified proteins that signal locally to regulate development and proliferation. The production of bioactive Wnts requires a number of dedicated factors in the secreting cell whose coordinated functions are not fully understood. A screen for small molecules identified inhibitors of vacuolar acidification as potent inhibitors of Wnt secretion. Inhibition of the V-ATPase or disruption of vacuolar pH gradients by diverse drugs potently inhibited Wnt/ß-catenin signaling both in cultured human cells and in vivo, and impaired Wnt-regulated convergent extension movements in Xenopus embryos. WNT secretion requires its binding to the carrier protein wntless (WLS); we find that WLS is ER-resident in human cells and WNT3A binding to WLS requires PORCN-dependent lipid modification of WNT3A at serine 209. Inhibition of vacuolar acidification results in accumulation of the WNT3A-WLS complex both in cells and at the plasma membrane. Modeling predictions suggest that WLS has a lipid-binding ß-barrel that is similar to the lipocalin-family fold. We propose that WLS binds Wnts in part through a lipid-binding domain, and that vacuolar acidification is required to release palmitoylated WNT3A from WLS in secretory vesicles, possibly to facilitate transfer of WNT3A to a soluble carrier protein.

Measuring the Frailty Phenotype and its Association with Cognition in Mid-Life and Older Age.

BACKGROUND: Frailty is directly linked to physical robustness and cognitive decline in older age. The Fried Frailty phenotype (FP) is a construct composed of five core symptoms that has been studied predominately in older age. There is little research contrasting the psychometric properties of the FP in mid-life versus older age. OBJECTIVE: We compared the psychometric properties of the FP in mid-life and older age and investigated relationships between the FP and cognition. METHODS: Frailty and neuropsychological assessments were completed on 361 adults, between 45 and 92 years of age, without primary neurological disorders. Confirmatory factor analysis was used to examine FP, indicated by Grip Strength, Gait Speed, Physical Activity, Fatigue, and Weight Loss. Measurement invariance was tested in mid-life (45-64 years) versus older age (≥65 years). Associations were examined between FP and language, executive functions, memory, processing speed, and visuospatial domains as well as a Generalized Cognition factor. Age was tested as a moderator of these associations. RESULTS: Weight Loss was a poor indicator of FP. Factor loadings were comparable across age groups; however, Fatigue was disproportionately higher among those in mid-life. FP was negatively associated with all cognitive domains and remained invariant across age groups. CONCLUSION: Results support the construct validity of the FP and document its stable associations with poorer cognition in middle and older life. Future research investigating central features of frailty earlier in life may offer avenues for developing targeted prevention measures and better characterization of individuals with elevated dementia risk.

Endoscopic biliary sphincterotomy is not required for transpapillary SEMS placement for biliary obstruction.

BACKGROUND: Endoscopic retrograde cholangiopancreatography with biliary self-expanding metal stent placement is the preferred method of providing biliary drainage for pancreaticobiliary malignancies. Some endoscopists routinely perform biliary sphincterotomy to facilitate biliary stent placement and potentially minimize pancreatitis with transpapillary self-expanding metal stent placement. AIMS: Our hypothesis was that biliary sphincterotomy has no effect on the success rate of transpapillary self-expanding metal stent placement and increases procedure-related complications. METHODS: In a retrospective analysis, outcomes of two groups were compared: (1) self-expanding metal stent placement without biliary sphincterotomy, (2) self-expanding metal stent placement with biliary sphincterotomy during the same procedure. Complications and stent patency rates were evaluated. RESULTS: There were 104 subjects included in the study. Post-sphincterotomy bleeding (p = 0.001) was associated with biliary sphincterotomy performed immediately prior to self-expanding metal stent placement. Importantly, self-expanding metal stent placement without biliary sphincterotomy was always technically successful and self-expanding metal stent placement without biliary sphincterotomy was not associated with pancreatitis. CONCLUSIONS: Patients who undergo biliary sphincterotomy during transpapillary self-expanding metal stent placement experience more immediate complications than those who do not. Biliary sphincterotomy was not associated with longer stent patency. Self-expanding metal stent placement without a biliary sphincterotomy was not associated with pancreatitis regardless of the type of self-expanding metal stent used (covered or uncovered). Of the patients without a biliary sphincterotomy, 100% had successful stent placement, further arguing against its use in this setting.

Neuropsychological correlates of subjective fatigue in non-demented older adults and the moderating effect of physical activity.

This study examined the association between self-reported fatigue and neuropsychological performance in 167 middle-aged and older (age range: 50-91 years) adults without dementia. Participants completed the Fatigue Symptom Inventory, a comprehensive neuropsychological evaluation, and frailty assessment. Higher levels of fatigue were significantly associated with poorer attention/information processing, executive functioning, and psychomotor speed, even after controlling for depression, sleep quality, physical weakness, and other covariates. Participants endorsing moderate-severe fatigue faced higher odds (OR = 6.6, 95% CI = 1.1, 39.1) of exhibiting clinical attention/information processing impairments than those without. Moderation analyses showed that fatigue was related to select cognitive deficits among those reporting mean or lower levels of activity, but not high levels. These findings highlight fatigue as an important clinical marker of select cognitive deficits in non-demented older adults that is distinct from the common confounding conditions examined in this study. High levels of physical activity may buffer this relationship.

Psammaplin A as a general activator of cell-based signaling assays via HDAC inhibition and studies on some bromotyrosine derivatives.

The Wnt signaling pathway regulates cell growth and development in metazoans, and is therefore of interest for drug discovery. By screening a library of 5808 pre-fractionated marine extracts in a cell-based Wnt signaling assay, several signaling activators and inhibitors were observed. LCMS-based fractionation rapidly identified an active compound from Pseudoceratina purpurea as psammaplin A, a known HDAC inhibitor. Other HDAC inhibitors similarly activated signaling in this assay, indicating HDAC inhibitors will be identified through many cell-based reporter assays. In a large scale analysis of P. purpurea, three previously undescribed bromotyrosine based natural products were identified; the structure of one of these was confirmed by synthesis. Additionally, three other derivatives of psammaplin A were prepared: a mixed disulfide and two sulfinate esters. Finally, evidence to support a structural reassignment of psammaplin I from a sulfone to the isomeric sulfinate ester is presented.

Posttraumatic cognitions, childhood sexual abuse characteristics, and posttraumatic stress disorder in men who have sex with men.

BACKGROUND: High rates of experience of childhood sexual abuse (CSA) among in men who have sex with men (MSM) place this population at increased risk for posttraumatic stress disorder (PTSD). OBJECTIVE: This study explores how specific characteristics of CSA relate to posttraumatic cognitions (PTCs) and explores the role that specific PTCs play in the relationship between CSA and PTSD in MSM. METHODS: Two-hundred and ninety MSM completed a CSA interview, the Davidson Trauma Scale, and the Posttraumatic Cognitions Inventory. RESULTS: Controlling for sociodemographic factors, CSA involving physical injury and CSA with intense fear were associated with higher levels of PTCs about the self and world, but not with self-blame. We did not find significant associations for CSA involving a family member, CSA with penetration, or duration or frequency of CSA with any subscale on the PTCI. Experiencing CSA for the first time during adolescence was associated with higher self-blame. Analyses revealed that physical injury and intense fear each had indirect effects on PTSD symptoms through negative cognitions about the self and world. First CSA episode during adolescence had an indirect effect on PTSD symptoms through self-blame. CSAs accounted for 16.7% and PTCs accounted for 31.7% of the variance in PTSD, underlining the importance of PTCs. CONCLUSIONS: Assessing for physical injury, intense fear, and age at first CSA are particularly relevant to PTCs and of critical importance to advancing assessment and treatment strategies for PTSD in MSM.

Revisiting eligibility for deep brain stimulation: Do preoperative mood symptoms predict outcomes in Parkinson's disease patients?

INTRODUCTION: Anxiety and depression are common in PD, occurring in an estimated 30%-40% of PD patients. However, the extent to which these emotional symptoms interfere with Deep Brain Stimulation (DBS) outcomes is not well established. This study examined the association between pre-operative emotional well-being and postsurgical cognitive, emotional, and motor performance in PD. METHODS: Forty-nine PD patients underwent neurological, neuropsychological (global cognition, processing speed, language, visuospatial, memory), and emotional assessments pre- and post-DBS. Fifteen patients were administered the UPDRS. Patients were divided into Anxious (Anx; n = 21), Comorbid Anxious and Depressed (Anx + Dep; n = 15), and Emotionally Asymptomatic (EA; n = 13) based on BAI and BDI-II cutoffs, and compared on pre-post changes in neurocognitive, mood, and motor scores using analyses of covariance (ANCOVA), controlling for education, ethnicity, and disease duration. RESULTS: Pre-DBS, there were no significant differences between the three groups on any neuropsychological measure. Overall change from pre-to post-DBS revealed declines on multiple cognitive measures and lower symptom endorsement on the BAI among all participants. No group differences were observed on neurocognitive measures, mood, or UPDRS. CONCLUSIONS: PD patients with mild-moderate anxiety or comorbid anxiety/depression pre-DBS do not show greater cognitive, emotional, and motor changes post-DBS compared to emotionally asymptomatic patients. These data emphasize the importance of discussing potential DBS outcomes, while keeping in mind that psychiatric comorbidity should not necessarily exclude patients from DBS. The notion that premorbid mood symptoms could disqualify a candidate for surgery would be a disservice, as this group performs comparably to asymptomatic peers.

Positive emotional well-being, health Behaviors, and inflammation measured by C-Reactive protein.

OBJECTIVE: There is a substantial body of literature describing the association between inflammatory biomarkers and negative emotional factors (i.e. depression). However, less is known about how they might be related to positive psychological variables. This study examined the association between positive emotional well-being (PEWB) and C-Reactive Protein (CRP), an inflammatory biomarker important for cardiovascular and other diseases. METHOD: Data were analyzed from 1979 respondents to a nationwide survey in the U.S., which included a chronically ill subgroup. Two aspects of PEWB were assessed; positive affect and life satisfaction. CRP was analyzed via blood-spot from a finger-prick. The mediating role of health behaviors (i.e., smoking, alcohol, BMI, and moderate exercise) was also examined. RESULTS: Both positive affect and life satisfaction were significantly related to lower CRP even after controlling for demographics and depression, in both the overall sample and chronically ill group. Only life satisfaction remained significantly related to CRP when controlling for health behaviors. When both depression and health behaviors were controlled, neither positive affect nor life satisfaction was significantly related to CRP. Moderate exercise emerged as the strongest mediator, followed by BMI and smoking. Individuals with low positive affect or low life satisfaction were at increased odds (OR = 1.40 and OR = 1.54, respectively) of having clinically elevated (≥3 mg/L) CRP. CONCLUSION: Our results add to a growing literature reporting an association between aspects of PEWB, especially life satisfaction, and a health-related biomarker of inflammation. Those with low positive affect or life satisfaction face increased risk of having clinically elevated CRP. Health behaviors, especially BMI and moderate exercise, account for some but not all of this relationship. Future studies should determine whether increasing life satisfaction and positive affect may contribute to improvements in health behaviors, inflammation, and better health outcomes.

Systematic review of transgastric ERCP in Roux-en-Y gastric bypass patients.

Balloon-assisted endoscopic retrograde cholangiopancreatoscopy (ERCP) in Roux-en-Y gastric bypass (RYGB) patients is technically challenging due to anatomic and accessory constraints, thus success rates are modest. Transgastric ERCP (TG-ERCP) offers a viable alternative. We aimed to systematically review the literature on TG-ERCP in RYGB patients to better define the technical approaches, success rates, and adverse events of this procedure. A computer-assisted search of the Embase and PubMed databases was performed to identify studies that focused on the techniques and clinical outcomes of TG-ERCP. Two investigators independently identified studies and abstracted relevant data. The literature search yielded 26 eligible studies comprising 509 TG-ERCP cases. Access to the excluded stomach to facilitate ERCP was achieved laparoscopically in 58% of reported cases, via open surgery (6% of reported cases), by antecedent placement of a percutaneous gastrostomy tube (33%), or with endoscopic ultrasound assistance (3%). Successful gastric access was reported in 100% of cases and successful ductal cannulation in 98.5%. Adverse events were reported in 14% of cases; 80% of these were related to gastrostomy creation and the rest were attributable to ERCP. Wound infections (n = 19, 3.7%) were the most common gastrostomy-related adverse event, and post-ERCP pancreatitis (n = 7, 1.4%) was the most common ERCP-related adverse event. No deaths were reported. Based on existing observational studies, TG-ERCP appears to be a safe and highly effective approach in patients with RYGB anatomy. Additional research and clinical experience are needed to more precisely define the risk-benefit ratio and optimal technique of TG-ERCP.

Modeling operant behavior in the Parkinsonian rat.

Mathematical principles of reinforcement (MPR; Killeen, 1994) is a quantitative model of operant behavior that contains three parameters representing motor capacity (delta), motivation (a), and short term memory (lambda). The present study applied MPR to characterize the effects of bilateral infusions of 6-OHDA into the substantia nigra pars compacta in the rat, a model of Parkinson's disease. Rats were trained to lever press under a 5-component fixed-ratio (5, 15, 30, 60, and 100) schedule of food reinforcement. Rats were tested for 15 days prior to dopamine lesions and again for 15 days post-lesion. To characterize functional loss relative to lesion size, rats were grouped according to the extent and the degree of lateralization of their dopamine loss. Response rates decreased as a function of dopamine depletion, primarily at intermediate ratios. MPR accounted for 98% of variance in pre- and post-lesion response rates. Consistent with reported disruptions in motor behavior induced by dopaminergic lesions, estimates of delta increased when dopamine was severely depleted. There was no support for different estimates of a based on pre- and post-lesion performance of any lesion group, suggesting that dopamine loss has negligible effects on incentive motivation. The present study demonstrates the usefulness of combining operant techniques with a theoretical model to better understand the effects of a neurochemical manipulation.