Change in medial frontal cerebral metabolite concentrations following bariatric surgery.

Obesity is associated with adverse effects on brain health, including an increased risk of neurodegenerative diseases. Changes in cerebral metabolism may underlie or precede structural and functional brain changes. While bariatric surgery is known to be effective in inducing weight loss and improving obesity-related medical comorbidities, few studies have examined whether it may be able to improve brain metabolism. In the present study, we examined changes in cerebral metabolite concentrations in participants with obesity who underwent bariatric surgery. Thirty-five patients with obesity (body mass index ≥ 35 kg/m2 ) were recruited from a bariatric surgery candidate nutrition class. They completed single voxel proton magnetic resonance spectroscopy at baseline (presurgery) and within 1 year postsurgery. Spectra were obtained from a large medial frontal brain region using a PRESS sequence on a 3-T Siemens Verio scanner. The acquisition parameters were TR = 3000 ms and TE = 37 ms. Tissue-corrected metabolite concentrations were determined using Osprey. Paired t-tests were used to examine within-subject change in metabolite concentrations, and correlations were used to relate these changes to other health-related outcomes, including weight loss and glycated hemoglobin (HbA1c ), a measure of blood sugar levels. Bariatric surgery was associated with a reduction in cerebral choline-containing compounds (Cho; t [34] = - 3.79, p < 0.001, d = -0.64) and myo-inositol (mI; t [34] = - 2.81, p < 0.01, d = -0.47) concentrations. There were no significant changes in N-acetyl-aspartate, creatine, or glutamate and glutamine concentrations. Reductions in Cho were associated with greater weight loss (r = 0.40, p < 0.05), and reductions in mI were associated with greater reductions in HbA1c (r = 0.44, p < 0.05). In conclusion, participants who underwent bariatric surgery exhibited reductions in cerebral Cho and mI concentrations, which were associated with improvements in weight loss and glycemic control. Given that elevated levels of Cho and mI have been implicated in neuroinflammation, reduction in these metabolites after bariatric surgery may reflect amelioration of obesity-related neuroinflammatory processes. As such, our results provide evidence that bariatric surgery may improve brain health and metabolism in individuals with obesity.

Neurometabolic timecourse of healthy aging.

PURPOSE: The neurometabolic timecourse of healthy aging is not well-established, in part due to diversity of quantification methodology. In this study, a large structured cross-sectional cohort of male and female subjects throughout adulthood was recruited to investigate neurometabolic changes as a function of age, using consensus-recommended magnetic resonance spectroscopy quantification methods. METHODS: 102 healthy volunteers, with approximately equal numbers of male and female participants in each decade of age from the 20s, 30s, 40s, 50s, and 60s, were recruited with IRB approval. MR spectroscopic data were acquired on a 3T MRI scanner. Metabolite spectra were acquired using PRESS localization (TE=30 ms; 96 transients) in the centrum semiovale (CSO) and posterior cingulate cortex (PCC). Water-suppressed spectra were modeled using the Osprey algorithm, employing a basis set of 18 simulated metabolite basis functions and a cohort-mean measured macromolecular spectrum. Pearson correlations were conducted to assess relationships between metabolite concentrations and age for each voxel; Spearman correlations were conducted where metabolite distributions were non-normal. Paired t-tests were run to determine whether metabolite concentrations differed between the PCC and CSO. Finally, robust linear regressions were conducted to assess both age and sex as predictors of metabolite concentrations in the PCC and CSO and separately, to assess age, signal-noise ratio, and full width half maximum (FWHM) linewidth as predictors of metabolite concentrations. RESULTS: Data from four voxels were excluded (2 ethanol; 2 unacceptably large lipid signal). Statistically-significant age*metabolite Pearson correlations were observed for tCho (r(98)=0.33, p<0.001), tCr (r(98)=0.60, p<0.001), and mI (r(98)=0.32, p=0.001) in the CSO and for NAAG (r(98)=0.26, p=0.008), tCho(r(98)=0.33, p<0.001), tCr (r(98)=0.39, p<0.001), and Gln (r(98)=0.21, p=0.034) in the PCC. Spearman correlations for non-normal variables revealed a statistically significant correlation between sI and age in the CSO (r(86)=0.26, p=0.013). No significant correlations were seen between age and tNAA, NAA, Glx, Glu, GSH, PE, Lac, or Asp in either region (all p>0.20). Age associations for tCho, tCr, mI and sI in the CSO and for NAAG, tCho, and tCr in the PCC remained when controlling for sex in robust regressions. CSO NAAG and Asp, as well as PCC tNAA, sI, and Lac were higher in women; PCC Gln was higher in men. When including an age*sex interaction term in robust regression models, a significant age*sex interaction was seen for tCho (F(1,96)=11.53, p=0.001) and GSH (F(1,96)=7.15, p=0.009) in the CSO and tCho (F(1,96)=9.17, p=0.003), tCr (F(1,96)=9.59, p=0.003), mI (F(1,96)=6.48, p=0.012), and Lac (F(1,78)=6.50, p=0.016) in the PCC. In all significant interactions, metabolite levels increased with age in females, but not males. There was a significant positive correlation between linewidth and age. Age relationships with tCho, tCr, and mI in the CSO and tCho, tCr, mI, and sI in the PCC were significant after controlling for linewidth and FWHM in robust regressions. CONCLUSION: The primary (correlation) results indicated age relationships for tCho, tCr, mI, and sI in the CSO and for NAAG, tCho, tCr, and Gln in the PCC, while no age correlations were found for tNAA, NAA, Glx, Glu, GSH, PE, Lac, or Asp in either region. Our results provide a normative foundation for future work investigating the neurometabolic time course of healthy aging using MRS.

Neuroimaging and Cognitive Evidence for Combined HIV-Alcohol Effects on the Central Nervous System: A Review.

Alcohol use disorder (AUD) among people living with HIV (PLWH) is a significant public health concern. Despite the advent of effective antiretroviral therapy, up to 50% of PLWH still experience worsened neurocognition, which comorbid AUD exacerbates. We report converging lines of neuroimaging and neuropsychological evidence linking comorbid HIV/AUD to dysfunction in brain regions linked to executive function, learning and memory, processing speed, and motor control, and consequently to impairment in daily life. The brain shrinkage, functional network alterations, and brain metabolite disruption seen in individuals with HIV/AUD have been attributed to several interacting pathways: viral proteins and EtOH are directly neurotoxic and exacerbate each other's neurotoxic effects; EtOH reduces antiretroviral adherence and increases viral replication; AUD and HIV both increase gut microbial translocation, promoting systemic inflammation and HIV transport into the brain by immune cells; and HIV may compound alcohol's damaging effects on the liver, further increasing inflammation. We additionally review the neurocognitive effects of aging, Hepatitis C coinfection, obesity, and cardiovascular disease, tobacco use, and nutritional deficiencies, all of which have been shown to compound cognitive changes in HIV, AUD, and in their comorbidity. Finally, we examine emerging questions in HIV/AUD research, including genetic and cognitive protective factors, the role of binge drinking in HIV/AUD-linked cognitive decline, and whether neurocognitive and brain functions normalize after drinking cessation.

Reduced Working Memory is Associated with Heavier Alcohol Consumption History, Role Impairment and Executive Function Difficulties.

Both HIV status and heavy alcohol use have been associated with reduced cognitive function, particularly in the domains of working memory and executive function. It is unclear what aspects of working memory and executive function are associated with HIV status and heavy alcohol use and whether performance on these measures are associated with functional impairment. We examined the relationship between HIV, history of heavy alcohol consumption, and HIV/alcohol interaction on speeded tests of frontal inhibitory abilities, a working memory task related to mental manipulation of letters and numbers, cognitive flexibility, and measures of functional impairment. Study participants included 284 individuals (151 HIV +) recruited from two different studies focusing on HIV associated brain dysfunction, one specific to the effects of alcohol, the other specific to the effects of aging. HIV status was not independently associated with working memory and executive function measures. Higher level of alcohol consumption was associated with reduced performance on Letter Number Sequencing. Poorer Letter Number Sequencing performance was associated with role impairment (an inability to do certain kinds of work, housework, or schoolwork) and executive function difficulties. Future studies should examine causal associations and interventions targeting working memory abilities.

RESUMEN: Tanto el estado del VIH como el consumo excesivo de alcohol se han asociado con una función cognitiva reducida, particularmente en los dominios de la memoria de trabajo y la función ejecutiva. No está claro qué aspectos de la memoria de trabajo y la función ejecutiva están asociados con el estado del VIH y el consumo excesivo de alcohol y si el desempeño en estas medidas está asociado con un deterioro funcional. Examinamos la relación entre el VIH, el historial de consumo excesivo de alcohol y la interacción VIH / alcohol, en pruebas aceleradas de capacidades inhibitorias frontales, tareas de memoria de trabajo relacionadas con la manipulación mental de letras y números, flexibilidad cognitiva y medidas de deterioro funcional. Los participantes del estudio incluyeron 284 personas (151 VIH +) reclutadas de dos estudios diferentes que se centran en la disfunción cerebral asociada al VIH, uno específico de los efectos del alcohol y el otro específico de los efectos del envejecimiento. El estado del VIH no se asoció de forma independiente con las medidas de memoria de trabajo y función ejecutiva. Un mayor nivel de consumo de alcohol se asoció con un rendimiento reducido en la secuenciación de números de letras. Un desempeño deficiente en la secuenciación de números de letras se asoció con un deterioro de los roles (una incapacidad para realizar ciertos tipos de trabajo, tareas domésticas o escolares) y dificultades en las funciones ejecutivas. Los estudios futuros deben examinar las asociaciones causales y las intervenciones dirigidas a las capacidades de la memoria de trabajo.

Attentional avoidance of threatening stimuli.

Aversive conditioning has been shown to influence the control of attention, such that aversively conditioned stimuli receive elevated priority. Although aversively conditioned but task-irrelevant distractors are known to capture attention during speeded search in rapid orienting tasks, it is unclear whether this bias extends to situations where orienting can be more deliberate. We demonstrate that punishment, via electric shock, does not give rise to oculomotor capture by shock-associated stimuli during a foraging task; rather, such aversively conditioned stimuli are actively avoided when searching through a display. On the other hand, even during a foraging task, we found some evidence for a covert attentional bias to threat. Our findings indicate that the previously described effects of aversive conditioning on visual search may not generalize beyond the initial glance and can be suppressed when conditions allow for more deliberate search strategies. More generally, our findings reveal that sustained attentional avoidance of aversively conditioned stimuli is possible during active search.

Measuring attention to reward as an individual trait: the value-driven attention questionnaire (VDAQ).

Reward history is a powerful determinant of what we pay attention to. This influence of reward on attention varies substantially across individuals, being related to a variety of personality variables and clinical conditions. Currently, the ability to measure and quantify attention-to-reward is restricted to the use of psychophysical laboratory tasks, which limits research into the construct in a variety of ways. In the present study, we introduce a questionnaire designed to provide a brief and accessible means of assessing attention-to-reward. Scores on the questionnaire correlate with other measures known to be related to attention-to-reward and predict performance on multiple laboratory tasks measuring the construct. In demonstrating this relationship, we also provide evidence that attention-to-reward as measured in the lab, an automatic and implicit bias in information processing, is related to overt behaviors and motivations in everyday life as assessed via the questionnaire. Variation in scores on the questionnaire is additionally associated with a distinct biomarker in brain connectivity, and the questionnaire exhibits acceptable test-retest reliability. Overall, the Value-Driven Attention Questionnaire (VDAQ) provides a useful proxy-measure of attention-to-reward that is much more accessible than typical laboratory assessments.

Association between cannabis use disorder and greater apathy in adults with HIV.

BACKGROUND: Apathy is prevalent among people with HIV (PWH) and is associated with poor clinical outcomes. Cannabis use and Cannabis Use Disorder (CUD) are also disproportionately prevalent among PWH. CUD and younger onset of cannabis use may be linked to apathy in the general population; however, patterns of use most strongly associated with apathy have not been firmly established, and it is unclear whether cannabis use is linked to apathy in PWH. METHODS: We examined associations in 311 adult PWH between Apathy Evaluation Scale-Self (AES-S) scores and CUD history (current/past/no CUD/no cannabis use) and between AES-S scores and age of CUD onset (adolescent-onset/adult-onset). We also examined robustness of associations to adjustment for depressive symptoms (which may overlap with apathy symptoms) and alcohol use. RESULTS: Current CUD was associated with greater AES-S scores relative to cannabis users with no CUD history (ß = 2.13, 95 % CI = 0.37-3.90, p = 0.018). Adolescent-onset CUD was not associated with greater apathy relative to adult-onset CUD (ß = 0.56, 95 % CI = -2.57 - 3.68, p = 0.7). Associations became nonsignificant after adjustment for depressive symptoms, but not after adjustment for alcohol use. Alcohol use was correlated with apathy (r = 0.19, 95 % CI: 0.076-0.29, p = 0.001). CONCLUSIONS: Cannabis Use Disorder and at-risk alcohol use are associated with apathy among PWH; this finding highlights the need for substance use disorder prevention and treatment among PWH.

Motivated suppression of value- and threat-modulated attentional capture.

Attention prioritizes stimuli previously associated with reward or punishment. The present study examined whether this attentional bias, widely considered to be involuntary and automatic, could be suppressed with sufficient motivation. Participants performed visual search for a shape-defined target. One color-singleton distractor predicted the possibility of receiving a reward and another an electric shock, with each outcome occurring infrequently. Participants were informed that the likelihood to earn a reward or avert punishment depended on fast and accurate performance, thus providing strong motivation to resist distraction by reward- and shock-related stimuli. Results revealed a reduction in the magnitude of attentional capture by reward- and threat-associated distractors, relative to neutral distractors, that persisted into extinction. In a second experiment, we replicated the suppression of value-modulated attentional capture in the absence of the shock condition, thus confirming that the suppression did not result from the presence of threat. Finally, in a third experiment, we replicated the typical pattern of attentional capture by reward cues using a more conventional procedure in which the motivation to suppress valent stimuli was low (the likelihood to be rewarded was high and not contingent on fast performance). This study demonstrates that signals for reward and threat can be actively suppressed with sufficient motivation. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Specificity and persistence of statistical learning in distractor suppression.

Statistical regularities in distractor location trigger suppression of high-probability distractor locations during visual search. The degree to which such suppression reflects generalizable, persistent changes in a spatial priority map has not been examined. We demonstrate that suppression of high-probability distractor locations persists after location probabilities are equalized and likely reflects a genuine reshaping of the priority map rather than more transient effects of selection history. Statistically learned suppression generalizes across contexts within a task during learning but does not generalize between task paradigms using unrelated stimuli in identical spatial locations. These findings suggest that stimulus features do play a role in learned spatial suppression, potentially gating the weights applied to a spatial priority map. However, the binding of location to context during learning is not automatic, in contrast to the previously reported interaction of location-based statistical learning and stimulus features. (PsycINFO Database Record (c) 2020 APA, all rights reserved).

On the automaticity of attentional orienting to threatening stimuli.

Attention is biased toward stimuli that have been associated with aversive outcomes in the past. This bias has previously been interpreted as reflecting automatic orienting toward threat signals. However, in many prior studies, either the threatening stimulus provided valuable predictive information, signaling the possibility of an otherwise unavoidable punishment and thereby allowing participants to brace themselves, or the aversive event could be avoided with fast and accurate task performance. Under these conditions, monitoring for threat could be viewed as an adaptive strategy. In the present study, fixating a color stimulus immediately resulted in a shock on some trials, providing a direct incentive not to look at the stimulus. Nevertheless, this contingency resulted in participants fixating the shock-associated stimulus more frequently than a neutral distractor matched for physical salience. Our findings demonstrate that threatening stimuli are automatically attended even when attending such stimuli is actually responsible for triggering the aversive event, providing compelling evidence for automaticity. (PsycInfo Database Record (c) 2020 APA, all rights reserved).

Selection history is relative.

Visual attention can be tuned to specific features to aid in visual search. The way in which these search strategies are established and maintained is flexible, reflecting goal-directed attentional control, but can exert a persistent effect on selection that remains even when these strategies are no longer advantageous, reflecting an attentional bias driven by selection history. Apart from feature-specific search, recent studies have shown that attention can be tuned to target-nontarget relationships. Here we tested whether a relational search strategy continues to bias attention in a subsequent task, where the relationally better color and former target color both serve as distractors (Experiment 1) or as potential targets (Experiment 2). We demonstrate that a relational bias can persist in a subsequent task in which color serves as a task-irrelevant feature, both impairing and facilitating visual search performance. Our findings extend our understanding of the relational account of attentional control and the nature of selection history effects on attention.

Selection history in context: Evidence for the role of reinforcement learning in biasing attention.

Attention is biased towards learned predictors of reward. The influence of reward history on attentional capture has been shown to be context-specific: When particular stimulus features are associated with reward, these features only capture attention when viewed in the context in which they were rewarded. Selection history can also bias attention, such that prior target features gain priority independently of reward history. The contextual specificity of this influence of selection history on attention has not been examined. In the present study, we demonstrate that the consequences of repetitive selection on attention robustly generalize across context, such that prior target features capture attention even in contexts in which they were never seen previously. Our findings suggest that the learning underlying attention driven by outcome-independent selection history differs qualitatively from the learning underlying value-driven attention, consistent with a distinction between associative and reinforcement learning mechanisms.

Angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers for prevention and treatment of nephropathy associated with type 2 diabetes mellitus.

Renal complications resulting from type 2 diabetes mellitus are costly and common. Finding optimal therapy is important for the prevention and management of diabetic nephropathy. Research has focused on antihypertensive agents that modify the renin-angiotensin-aldosterone system. Because of their effects on the glomerulus, angiotensin-converting enzyme (ACE) inhibitors and angiotensin II receptor blockers (ARBs) have been studied as interventions at various stages of diabetic nephropathy. The ACE inhibitors may delay the progression to microalbuminuria and then clinical albuminuria. The ARBs decrease albuminuria in patients with microalbuminuria and decrease adverse renal events, specifically the progression to end-stage renal disease in patients with clinical albuminuria and hypertension. Limited data suggest that combination therapy with ACE inhibitors and ARBs may slow the progression of microalbuminuria to clinical albuminuria. Because of the variability in degree of albuminuria evaluated and in study designs (numbers of patients, study duration, drug dosages, and outcomes measured), a detailed review of the available literature about ACE inhibitors and ARBs in the prevention or treatment of diabetic nephropathy may provide insight to clinicians.

A Progressive, Collaborative Process to Improve a Curriculum and Define an Assessment Program.

OBJECTIVE: To revise the University of Oklahoma College of Pharmacy's professional program outcomes and create an assessment map using results from previous peer review and mapping of all professional courses and curricular streams of knowledge, skills, and attitudes (KSAs). DESIGN: After consolidating 15 original program outcomes into 11 more precise outcome statements, defining KSAs for each, and getting faculty approval of them, the committee detailed measurable program expectations upon graduation for each outcome and created an assessment map identifying where KSAs were taught, how they were to be assessed, and the expected ability level (novice, competent, proficient) for each across the curriculum. ASSESSMENT: The committee's work identified deficits, inconsistencies, and disproportionalities in professional program assessment. It recommended assessments to capture student achievement of each outcome, identified performance levels and criteria to measure outcomes progressively in each professional year, and outlined a process to provide students periodic reports on their progress in achieving each outcome. CONCLUSION: This work establishes a firm foundation for ongoing efforts to measure effectiveness of the professional program, especially in light of Accreditation Council for Pharmacy Education's (ACPE) revised accreditation standards.

The epidemiology of mesothelioma.

It has been more than 40 years since occupational crocidolite exposure in South African miners was found to be associated with development of malignant mesothelial tumors 30 to 40 years later. Similar cases were not seen in the amosite and chrysotile miners. Since then, epidemiological and toxicological knowledge have increased enormously, but mortality continues to rise steeply (5% to 10% per year) in most industrialized countries. Even with widespread asbestos abatement efforts, this increase is likely to continue in Western Europe and the United State well into the next century, at least until 2020. Unregulated use of asbestos in less industrialized countries may cause the epidemic to continue throughout the next century in those regions. Asbestos abatement seems to be successful as evidenced by a decline in the proportion of patients with peritoneal tumors, which are the most common malignancies in heavily exposed individuals. Whereas in the 1960s peritoneal tumors comprised up to 30% of the total, in recent years the proportion has fallen to about 10%, This changing ratio could also be due to the steady increase in pleural tumors. The difficulty in formulating the connection as to the etiology of mesothelioma resulted from an unforeseeable difference in the carcinogenicity of various asbestos and mineral fiber types and was compounded by the very long latency of the disease. Unfortunately, the use of a single term, "asbestos," to describe at least five fibrous silicate minerals, each with unique physical, chemical, and biological properties and not infrequently and naturally admixed, severely hampered scientific investigation into the occupational health risks. The field became confused and filled with debate. At the heart of the fiber type controversy lies a fundamentally differing view of the importance of biopersistence of various asbestos fibers in carcinogenesis. This review will deal with the epidemiology of mesothelioma with particular attention to the studies that elucidate the impact of various asbestos fiber types on the etiology of the disease.

Diabetes enhances apoptosis induced by cerebral ischemia.

The aim of this study is to explore the mechanism by which diabetes exaggerates cerebral stroke and its outcome. Since ischemia can be related to not only necrosis but apoptosis as well, we compared the development of apoptosis in STZ-diabetic rats and STZ-diabetic rats subjected to occlusion of the middle cerebral artery (MCA). 24-48 hr following MCA occlusion the animals were killed, the brain removed and prepared for evaluation by several indexes of apoptosis: nucleosomal DNA fragmentation, TUNEL staining, activation of caspase-3 and alteration in the expression of Bax and Bcl2. DNA fragmentation was not detected in the cortex of normal and diabetic animals, but was evident following MCA occlusion in diabetic rats. Bax expression was increased in the cortex of normal rats following MCA occlusion and this expression was further increased in the cortex of MCA occluded diabetic rats. Bcl2 expression was not changed in any of the groups. In the hippocampus, DNA fragmentation was not evident in control rats but was observed in diabetic rats. Ischemic injury did not enhance DNA laddering in diabetic animals. The expression of Bax was increased in diabetic rats but was not increased following MCA occlusion. Bcl2 expression was not changed by ischemia in any of the animal models. These data suggest that diabetes may enhance the development of stroke via increased cortical apoptotic activity but this was not additive in the hippocampus following ischemic injury.

Practice experiences at a single institutional practice site to improve advanced pharmacy practice examination performance.

OBJECTIVE: To determine whether sequential assignment of students to the same facility for institutional practice experiences improves their advanced pharmacy practice experience (APPE) examination scores. DESIGN: Student volunteers were assigned to the same healthcare facility for all institutional introductory pharmacy practice experiences (IPPEs) and advanced pharmacy practice experiences (APPEs). Other students completed institutional IPPEs and APPEs at separate healthcare facilities, ranging from 2 to 4 different facilities per student. APPE examination scores of students assigned to the same facility for all institutional learning experiences were compared with those of students assigned to more than 1 institutional practice site. ASSESSMENT: Holding grade point average constant, students assigned to the same facility for institutional IPPEs and APPEs scored 3 percentage points higher on the APPE institutional examination compared with students assigned to separate facilities for these experiences. CONCLUSION: Assigning students to the same facility for both institutional IPPEs and APPEs positively influenced knowledge-based APPE examination performance.

Incremental development of an integrated assessment method for the professional curriculum.

OBJECTIVE: To incrementally create and embed biannual integrated knowledge and skills examinations into final examinations of the pharmacy practice courses offered in the first 3 years of the pharmacy curriculum that would account for 10% of each course's final course grade. DESIGN: An ad hoc integrated examination committee was formed and tasked with addressing 4 key questions. Integrated examination committees for the first, second, and third years of the curriculum were established and tasked with identifying the most pertinent skills and knowledge-based content from each required course in the curriculum, developing measurable objectives addressing the pertinent content, and creating or revising multiple-choice and performance-based questions derived from integrated examination objectives. An Integrated Examination Review Committee evaluated all test questions, objectives, and student performance on each question, and revised the objectives and questions as needed for the following year's iteration. Eight performance objectives for the examinations were measured. ASSESSMENT: All 8 performance objectives were achieved. Sixty-four percent of the college's faculty members participated in the integrated examination process, improving the quality of the examination. The incremental development and implementation of the examinations over a 3-year period minimized the burden on faculty time while engaging them in the process. Student understanding of expectations for knowledge and skill retention in the curriculum also improved. CONCLUSIONS: Development of biannual integrated examinations in the first 3 years of the classroom curriculum enhanced the college's culture of assessment and addressed accreditation guidelines for formative and summative assessment of students' knowledge and skills. The course will continue to be refined each year.