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Purpose of Review: This review provides a concise overview of the recent literature regarding preoperative and postoperative neurocognitive functioning (NCF) in patients with glioma. Brief discussion also covers contemporary intraoperative brain mapping work, with a focus on potential influence of mapping upon NCF outcomes following awake surgery. Recent Findings: Most patients with glioma exhibit preoperative NCF impairment, with severity varying by germ line and tumoral genetics, tumor grade, and lesion location, among other characteristics. Literature regarding postoperative NCF changes is mixed, though numerous studies indicate a majority of patients exhibit immediate and short-term worsening. This is often followed by recovery over several months; however, a substantial portion of patients harbor persisting declines. Decline appears related to surgically-induced structural and functional brain alterations, both local and distal to the tumor and resection cavity. Importantly, NCF decline may be mitigated to some extent by intraoperative brain mapping, including mapping of both language-mediated and nonverbal functions. Summary: Research regarding perioperative NCF in patients with glioma has flourished over recent years. While this has increased our understanding of contributors to NCF and risk of decline associated with surgical intervention, more work is needed to better preserve NCF throughout the disease course. [ABSTRACT FROM AUTHOR]

Background: Pulmonary ionocytes have been identified in the airway epithelium as a small population of ion transporting cells expressing high levels of CFTR (cystic fibrosis transmembrane conductance regulator), the gene mutated in cystic fibrosis. By providing an infinite source of airway epithelial cells (AECs), the use of human induced pluripotent stem cells (hiPSCs) could overcome some challenges of studying ionocytes. However, the production of AEC epithelia containing ionocytes from hiPSCs has proven difficult. Here, we present a platform to produce hiPSC-derived AECs (hiPSC-AECs) including ionocytes and investigate their role in the airway epithelium. Methods: hiPSCs were differentiated into lung progenitors, which were expanded as 3D organoids and matured by air-liquid interface culture as polarised hiPSC-AEC epithelia. Using CRISPR/Cas9 technology, we generated a hiPSCs knockout (KO) for FOXI1, a transcription factor that is essential for ionocyte specification. Differences between FOXI1 KO hiPSC-AECs and their wild-type (WT) isogenic controls were investigated by assessing gene and protein expression, epithelial composition, cilia coverage and motility, pH and transepithelial barrier properties. Results: Mature hiPSC-AEC epithelia contained basal cells, secretory cells, ciliated cells with motile cilia, pulmonary neuroendocrine cells (PNECs) and ionocytes. There was no difference between FOXI1 WT and KO hiPSCs in terms of their capacity to differentiate into airway progenitors. However, FOXI1 KO led to mature hiPSC-AEC epithelia without ionocytes with reduced capacity to produce ciliated cells. Conclusion: Our results suggest that ionocytes could have role beyond transepithelial ion transport by regulating epithelial properties and homeostasis in the airway epithelium. [ABSTRACT FROM AUTHOR]

Over the past decade, the improvement in cancer diagnostics and therapeutics has extended the overall survival of patients diagnosed with cancer including brain cancer. However, despite these unprecedented medical successes, patients continue to experience numerous neurologic complications after treatment that interfere with their independence, functionality, and overall quality of life. These include, among others, cognitive impairment, endocrinopathies, peripheral and cranial neuropathies, and vasculopathy. This article describes the long-term neurologic complications cancer survivors commonly experience to increase awareness of these complications and discuss treatments when available. Further research is necessary to understanding of mechanisms of neurologic injury and advance diagnosis and treatment. Effective patient education, monitoring, and managing neurologic issues after cancer treatment may improve independence, functionality, and quality of life during survivorship. [ABSTRACT FROM AUTHOR]

Some residues in the cystic fibrosis transmembrane conductance regulator (CFTR) channel are the site of more than one CFTR variant that cause cystic fibrosis. Here, we investigated the function of S1159F and S1159P, two variants associated with different clinical phenotypes, which affect the same pore‐lining residue in transmembrane segment 12 that are both strongly potentiated by ivacaftor when expressed in CFBE41o− bronchial epithelial cells. To study the single‐channel behaviour of CFTR, we applied the patch‐clamp technique to Chinese hamster ovary cells heterologously expressing CFTR variants incubated at 27°C to enhance channel residence at the plasma membrane. S1159F‐ and S1159P‐CFTR formed Cl− channels activated by cAMP‐dependent phosphorylation and gated by ATP that exhibited thermostability at 37°C. Both variants modestly reduced the single‐channel conductance of CFTR. By severely attenuating channel gating, S1159F‐ and S1159P‐CFTR reduced the open probability (Po) of wild‐type CFTR by ≥75% at ATP (1 mM); S1159F‐CFTR caused the greater decrease in Po consistent with its more severe clinical phenotype. Ivacaftor (10–100 nM) doubled the Po of both CFTR variants without restoring Po values to wild‐type levels, but concomitantly, ivacaftor decreased current flow through open channels. For S1159F‐CFTR, the reduction of current flow was marked at high (supersaturated) ivacaftor concentrations (0.5–1 μM) and voltage‐independent, identifying an additional detrimental action of elevated ivacaftor concentrations. In conclusion, S1159F and S1159P are gating variants, which also affect CFTR processing and conduction, but not stability, necessitating the use of combinations of CFTR modulators to optimally restore their channel activity. Key points: Dysfunction of the ion channel cystic fibrosis transmembrane conductance regulator (CFTR) causes the genetic disease cystic fibrosis (CF).This study investigated two rare pathogenic CFTR variants, S1159F and S1159P, which affect the same amino acid in CFTR, to understand the molecular basis of disease and response to the CFTR‐targeted therapy ivacaftor.Both rare variants diminished CFTR function by modestly reducing current flow through the channel and severely inhibiting ATP‐dependent channel gating with S1159F exerting the stronger adverse effect, which correlates with its association with more severe disease.Ivacaftor potentiated channel gating by both rare variants without restoring their activity to wild‐type levels, but concurrently reduced current flow through open channels, particularly those of S1159F‐CFTR.Our data demonstrate that S1159F and S1159P cause CFTR dysfunction by multiple mechanisms that require combinations of CFTR‐targeted therapies to fully restore channel function. [ABSTRACT FROM AUTHOR]

This document provides an overview of experimental pharmacology in precision medicine, focusing on recent advancements and challenges in the field. It discusses the application of precision medicine in areas such as drug metabolism, drug-drug interactions, therapeutic drug dose monitoring, and interventions for cystic fibrosis. The article also mentions the 19th World Congress of Basic & Clinical Pharmacology (WCP2023), which explored precision medicine approaches for improving human health. The importance of molecular information and quantitative proteomics in enhancing drug safety and efficacy, as well as predicting individual variations in drug absorption, distribution, metabolism, and elimination, is emphasized. The document highlights the success and challenges of precision medicine in specific cases, including drug-drug interactions, targeted cancer therapies, and cystic fibrosis. It also underscores the significance of collaboration between patient advocacy groups, academia, industry, and regulatory authorities in advancing precision medicine. [Extracted from the article]

Subjective cognitive decline (SCD) is a risk factor for dementia that may occur at higher rates in people with HIV (PWH). Prospective memory (PM) is an aspect of cognition that may help us better understand how SCD impacts daily life. Paricipants were 62 PWH aged ≥ 50 years and 33 seronegative individuals. SCD was operationalized as normatively elevated cognitive symptoms on standardized questionnaires, but with normatively unimpaired performance-based cognition and no current affective disorders. PM was measured with the Comprehensive Assessment of Prospective Memory (CAPM), the Cambridge Test of Prospective Memory (CAMPROMPT), and an experimental computerized time-based PM task. A logistic regression revealed that older PWH had a three-fold increased likelihood for SCD. Among the PWH, SCD was associated with more frequent PM symptoms and poorer accuracy on the time-based scale of the CAMPROMPT. These findings suggest that SCD disrupts PM in older PWH. [ABSTRACT FROM AUTHOR]

Alcohol use is associated with memory problems in young adults with HIV, but the cognitive mechanisms of that association are not known. Sixty adults (aged 19–24 years) living with HIV were administered the Alcohol, Smoking, and Substance Involvement Screening Test to assess alcohol use, Behavior Rating Inventory of Executive Function for self-reported executive functions, and the Prospective and Retrospective Memory Questionnaire (PRMQ) for dailiy memory functioning. Controlling for mood, self-reported executive functions fully mediated the relationship between alcohol use and memory (indirect effect b=.568, 95%CI [.209,.888]). Findings suggest that self-reported executive dysregulation of memory processes (e.g., Strategic encoding and retrieval) may drive the effects of alcohol use on daily memory symptoms. [ABSTRACT FROM AUTHOR]

Objective:Prospective memory (PM) or "remembering to remember" has been shown to be reduced in Veterans with histories of mild traumatic brain injury (mTBI), particularly on tasks with high strategic demands such as recalling time-based information in the absence of external cues. This study examined whether time monitoring during a PM task was reduced in Veterans with a history of mTBI and was associated with time-based PM performance. Method:Veterans with a history of mTBI (n = 49) and Veterans without a history of TBI (n = 16) completed the Memory for Intentions Screening Test (MIST) as a measure of PM during which their time monitoring (i.e. number of clock checks) was recorded. Results:Adjusting for age, education, depression, and PTSD symptoms, negative binomial regression revealed that the mTBI group checked the clock less frequently compared to the control group (Cohen's d = 0.84, p = 0.005). Within the mTBI group, less frequent time monitoring across the entire MIST task was associated with poorer time-based MIST performance (rs =.57, p < 0.001), but not with event-based MIST (rs =.04, p = 0.768). Conclusions:Veterans with a history of mTBI evidenced significantly reduced time monitoring during a PM task compared to Veterans without a history mTBI, which was associated with strategically-demanding PM. Current findings provide that mTBI-associated difficulties with strategic aspects of PM may be due to reduced time monitoring. Future studies are needed to determine if reduced time monitoring also contributes to mTBI-associated PM difficulties in the real-world (e.g. medication non-adherence). [ABSTRACT FROM AUTHOR]

ObjectiveThe Internet serves an increasingly critical role in health behaviors for older adults with chronic medical conditions. Guided by theories of health behaviors and literacy, this study examined whether the relationship between educational attainment and online pharmacy skills in older persons with HIV disease (PWH) is mediated by health literacy. Design: Participants included 98 PWH age 50 and older who completed the Test of Online Pharmacy Skills (TOPS), which required them to navigate an experimenter-controlled online pharmacy to perform several naturalistic tasks (e.g., refill an existing prescription). Participants also completed the Medication-Management Test-Revised (MMT-R). Results: Mediation analyses revealed a significant indirect effect of education on both online pharmacy accuracy and MMT-R, which was fully mediated by health literacy. In contrast, there was no direct or indirect effect of education on online pharmacy speed when health literacy was included as a mediator. Conclusion: Health literacy plays an important role in the relationship between years of education attained and the ability of older PWH to successfully navigate online pharmacy tasks and manage their medications. Future studies might examine whether interventions to improve electronic health literacy among older PWH who have lower educational attainment have beneficial effects on online health behaviors. [ABSTRACT FROM AUTHOR]

Objective Mild traumatic brain injury (mTBI) and posttraumatic stress disorder (PTSD) frequently co-occur and are associated with neurocognitive intra-individual variability (IIV) and difficulty with prospective memory (PM). The current study aimed to examine associations between IIV and PM in this comorbid group. Method Fifty veterans with a history of blast mTBI and current comorbid PTSD completed a standardized neurocognitive battery to measure IIV, and the Memory for Intentions Screening Test measuring PM. Results Adjusting for age, education, and race, higher IIV was associated with poorer time-based PM (p  < .001, f2  = .34), but not event-based PM. In a subset of the sample with self-report data, higher IIV was associated with poorer self-reported retrospective memory, but not PM. Conclusions Cognitive variability on a standardized neuropsychological battery was associated with strategically demanding PM, which is an ecologically relevant ability and highlights the possible connection between subtle cognitive difficulties in-clinic and those experienced in daily life. [ABSTRACT FROM AUTHOR]

Objective: Women are becoming more prevalent in clinical neuropsychology, but gender bias and disparities persist across multiple professional domains. This study examined potential gender disparities in historical authorship trends across commonly read journals in clinical neuropsychology. Method: Analyses were conducted on 10,531 articles published in six clinical neuropsychology journals from 1985 to 2019. Each author was coded as either a man or a woman using the OpenGenderTracking Project database. Results: On average, women comprised 43.3% (±30.6) of the authors listed in clinical neuropsychology article bylines and were lead and/or corresponding author on 50.3% of these papers. Findings varied by journal, with Child Neuropsychology having the best representation of women across several study metrics. Women comprised an increasing proportion of authors over time and the gender gap in clinical neuropsychology is smaller than was recently reported for the broader field of psychology; nevertheless, the recent rates of women as authors lag behind the prevalence of women in clinical neuropsychology. Encouragingly, gender was not associated with the number of times an article was cited. Articles that included women in leadership roles had significantly more authors overall and specifically more women authors. Conclusions: Women are under-represented as authors in clinical neuropsychology journals, but they are becoming more common and their papers are cited just as frequently as men. Efforts to increase women as research mentors and sponsors may help to further close the publishing gender gap in clinical neuropsychology. [ABSTRACT FROM AUTHOR]

Cystic fibrosis (CF) is caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. Defective CFTR leads to accumulation of dehydrated viscous mucus within the small intestine, luminal acidification and altered intestinal motility, resulting in blockage. These changes promote gut microbial dysbiosis, adversely influencing the normal proliferation and differentiation of intestinal epithelial cells. Using Illumina 16S rRNA gene sequencing and immunohistochemistry, we assessed changes in mucosa-attached microbiome and epithelial cell profile in the small intestine of CF mice and a CF patient compared to wild-type mice and non-CF humans. We found increased abundance of pro-inflammatory Escherichia and depletion of beneficial secondary bile-acid producing bacteria in the ileal mucosa-attached microbiome of CFTR-null mice. The ileal mucosa in a CF patient was dominated by a non-aeruginosa Pseudomonas species and lacked numerous beneficial anti-inflammatory and short-chain fatty acid-producing bacteria. In the ileum of both CF mice and a CF patient, the number of absorptive enterocytes, Paneth and glucagon-like peptide 1 and 2 secreting L-type enteroendocrine cells were decreased, whereas stem and goblet cell numbers were increased. These changes in mucosa-attached microbiome and epithelial cell profile suggest that microbiota-host interactions may contribute to intestinal CF disease development with implications for therapy. [ABSTRACT FROM AUTHOR]

Cystic fibrosis (CF) is caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. Defective CFTR leads to accumulation of dehydrated viscous mucus within the small intestine, luminal acidification and altered intestinal motility, resulting in blockage. These changes promote gut microbial dysbiosis, adversely influencing the normal proliferation and differentiation of intestinal epithelial cells. Using Illumina 16S rRNA gene sequencing and immunohistochemistry, we assessed changes in mucosa-attached microbiome and epithelial cell profile in the small intestine of CF mice and a CF patient compared to wild-type mice and non-CF humans. We found increased abundance of pro-inflammatory Escherichia and depletion of beneficial secondary bile-acid producing bacteria in the ileal mucosa-attached microbiome of CFTR-null mice. The ileal mucosa in a CF patient was dominated by a non-aeruginosa Pseudomonas species and lacked numerous beneficial anti-inflammatory and short-chain fatty acid-producing bacteria. In the ileum of both CF mice and a CF patient, the number of absorptive enterocytes, Paneth and glucagon-like peptide 1 and 2 secreting L-type enteroendocrine cells were decreased, whereas stem and goblet cell numbers were increased. These changes in mucosa-attached microbiome and epithelial cell profile suggest that microbiota-host interactions may contribute to intestinal CF disease development with implications for therapy. [ABSTRACT FROM AUTHOR]

Background and Purpose: Cystic fibrosis transmembrane conductance regulator (CFTR) potentiators are small molecules developed to treat the genetic disease cystic fibrosis (CF). They interact directly with CFTR Cl− channels at the plasma membrane to enhance channel gating. Here, we investigate the action of a new CFTR potentiator, CP‐628006 with a distinct chemical structure. Experimental Approach Using electrophysiological assays with CFTR‐expressing heterologous cells and CF patient‐derived human bronchial epithelial (hBE) cells, we compared the effects of CP‐628006 with the marketed CFTR potentiator ivacaftor. Key Results: CP‐628006 efficaciously potentiated CFTR function in epithelia from cultured hBE cells. Its effects on the predominant CFTR variant F508del‐CFTR were larger than those with the gating variant G551D‐CFTR. In excised inside‐out membrane patches, CP‐628006 potentiated wild‐type, F508del‐CFTR, and G551D‐CFTR by increasing the frequency and duration of channel openings. CP‐628006 increased the affinity and efficacy of F508del‐CFTR gating by ATP. In these respects, CP‐628006 behaved like ivacaftor. CP‐628006 also demonstrated notable differences with ivacaftor. Its potency and efficacy were lower than those of ivacaftor. CP‐628006 conferred ATP‐dependent gating on G551D‐CFTR, whereas the action of ivacaftor was ATP‐independent. For G551D‐CFTR, but not F508del‐CFTR, the action of CP‐628006 plus ivacaftor was greater than ivacaftor alone. CP‐628006 delayed, but did not prevent, the deactivation of F508del‐CFTR at the plasma membrane, whereas ivacaftor accentuated F508del‐CFTR deactivation. Conclusions and Implications: CP‐628006 has distinct effects compared to ivacaftor, suggesting a different mechanism of CFTR potentiation. The emergence of CFTR potentiators with diverse modes of action makes therapy with combinations of potentiators a possibility. [ABSTRACT FROM AUTHOR]

Dysfunction of the epithelial anion channel cystic fibrosis transmembrane conductance regulator (CFTR) causes a wide spectrum of disease, including cystic fibrosis (CF) and CFTR‐related diseases (CFTR‐RDs). Here, we investigate genotype–phenotype–CFTR function relationships using human nasal epithelial (hNE) cells from a small cohort of non‐CF subjects and individuals with CF and CFTR‐RDs and genotypes associated with either residual or minimal CFTR function using electrophysiological techniques. Collected hNE cells were either studied directly with the whole‐cell patch‐clamp technique or grown as primary cultures at an air–liquid interface after conditional reprogramming. The properties of cAMP‐activated whole‐cell Cl− currents in freshly isolated hNE cells identified them as CFTR‐mediated. Their magnitude varied between hNE cells from individuals within the same genotype and decreased in the rank order: non‐CF > CFTR residual function > CFTR minimal function. CFTR‐mediated whole‐cell Cl− currents in hNE cells isolated from fully differentiated primary cultures were identical to those in freshly isolated hNE cells in both magnitude and behaviour, demonstrating that conditional reprogramming culture is without effect on CFTR expression and function. For the cohort of subjects studied, CFTR‐mediated whole‐cell Cl− currents in hNE cells correlated well with CFTR‐mediated transepithelial Cl− currents measured in vitro with the Ussing chamber technique, but not with those determined in vivo with the nasal potential difference assay. Nevertheless, they did correlate with the sweat Cl− concentration of study subjects. Thus, this study highlights the complexity of genotype–phenotype–CFTR function relationships, but emphasises the value of conditionally reprogrammed hNE cells in CFTR research and therapeutic testing. Key points: The genetic disease cystic fibrosis is caused by pathogenic variants in the cystic fibrosis transmembrane conductance regulator (CFTR), an ion channel, which controls anion flow across epithelia lining ducts and tubes in the body.This study investigated CFTR function in nasal epithelial cells from people with cystic fibrosis and CFTR variants with a range of disease severity.CFTR function varied widely in nasal epithelial cells depending on the identity of CFTR variants, but was unaffected by conditional reprogramming culture, a cell culture technique used to grow large numbers of patient‐derived cells.Assessment of CFTR function in vitro in nasal epithelial cells and epithelia, and in vivo in the nasal epithelium and sweat gland highlights the complexity of genotype–phenotype–CFTR function relationships. [ABSTRACT FROM AUTHOR]

Objective: Memory symptoms and objective impairment are common in HIV disease and are associated with disability. A paradoxical issue is that objective episodic memory failures can interfere with accurate recall of memory symptoms. The present study assessed whether responses on a self-report scale of memory symptoms demonstrate measurement invariance in persons with and without objective HIV-associated memory impairment. Method: In total, 505 persons with HIV completed the Prospective and Retrospective Memory Questionnaire (PRMQ). Objective memory impairment (n = 141) was determined using a 1-SD cutoff on clinical tests of episodic memory. PRMQ measurement invariance was assessed by confirmatory factor analyses examining a one-factor model with increasing cross-group equality constraints imposed on factor loadings and item thresholds (i.e., configural, weak, and strong invariance). Results: Configural model fit indicated that identical items measured a one-factor model for both groups. Comparison to the weak model indicated that factor loadings were equivalent across groups. However, there was evidence of partial strong invariance, with two PRMQ item thresholds differing across memory impairment groups. Post hoc analyses using a 1.5-SD memory impairment cutoff (n = 77) revealed both partial weak and partial strong invariance, such that PRMQ item loadings differed across memory groups for three items. Conclusions: The PRMQ demonstrated a robust factor structure among persons with and without objective HIV-associated memory impairment. However, on select PRMQ items, individuals with memory impairment reported observed scores that were relatively higher than their latent score, while items were more strongly associated with the memory factor in a group with greater memory impairment. [ABSTRACT FROM AUTHOR]

The gasotransmitter carbon monoxide (CO) regulates fluid and electrolyte movements across epithelial tissues. However, its action on anion channels is incompletely understood. Here, we investigate the direct action of CO on the cystic fibrosis transmembrane conductance regulator (CFTR) by applying CO-releasing molecules (CO-RMs) to the intracellular side of excised inside-out membrane patches from cells heterologously expressing wild-type human CFTR. Addition of increasing concentrations of tricarbonyldichlororuthenium(II) dimer (CORM-2) (1–300 μM) inhibited CFTR channel activity, whereas the control RuCl3 (100 μM) was without effect. CORM-2 predominantly inhibited CFTR by decreasing the frequency of channel openings and, hence, open probability (Po). But, it also reduced current flow through open channels with very fast kinetics, particularly at elevated concentrations. By contrast, the chemically distinct CO-releasing molecule CORM-3 inhibited CFTR by decreasing Po without altering current flow through open channels. Neither depolarizing the membrane voltage nor raising the ATP concentration on the intracellular side of the membrane affected CFTR inhibition by CORM-2. Interestingly, CFTR inhibition by CORM-2, but not by CFTRinh-172, was prevented by prior enhancement of channel activity by the clinically approved CFTR potentiator ivacaftor. Similarly, when added after CORM-2, ivacaftor completely relieved CFTR inhibition. In conclusion, CORM-2 has complex effects on wild-type human CFTR consistent with allosteric inhibition and open-channel blockade. Inhibition of CFTR by CO-releasing molecules suggests that CO regulates CFTR activity and that the gasotransmitter has tissue-specific effects on epithelial ion transport. The action of ivacaftor on CFTR Cl− channels inhibited by CO potentially expands the drug’s clinical utility. [ABSTRACT FROM AUTHOR]

Objective: Older adults commonly experience declines in everyday functioning, the reasons for which are multifactorial. Prospective memory (PM), or remembering to carry out intended actions, can be an executively demanding cognitive process that declines with older age and is independently associated with a variety of everyday functions (e.g. taking medication). This study examined the hypothesis that PM mediates the relationship between older age and poorer everyday functioning. Method: A total of 468 community-dwelling adults (ages 18–75) with a range of medical comorbidities (e.g. viral infection) were classified as dependent on four well-validated measures of manifest everyday functioning: activities of daily living, employment status, the Karnofsky Scale of Performance Status, and self-reported cognitive symptoms. Participants completed the Memory for Intentions Test (MIsT) to measure PM, alongside clinical tests of executive functions and retrospective memory. Results: Controlling for education and comorbidities, bootstrap analysis revealed a significant direct effect of age on everyday functioning and a significant mediated effect of age on everyday functioning through the indirect effect of time-based b =.006 [.003,.010] and event-based PM (b =.005, [.002,.009]), as well as slightly smaller effects for executive functions (b =.003, [.001,.005]) and retrospective memory (b =.002, [.001,.005]). Conclusions: These cross-sectional data suggest that executively demanding aspects of declarative memory play an important partial mediating role between an individual factor (i.e. age) and daily life activities, and highlight the possible benefit of targeting PM for improving everyday functioning in older adults. [ABSTRACT FROM AUTHOR]

Objective: We investigated the construct and criterion validity of the source memory (SM) indices within the California Verbal Learning Test-II (CVLT-II). Method: Participants included 77 individuals with HIV-associated neurocognitive disorders (HAND+), 287 HIV + neurocognitively normal individuals (HAND−) and 203 seronegative HIV comparisons (HIV−). CVLT-II SM impairment status (normative scores ≤1 standard deviation) was determined using Total Across-List Intrusions and Source Recognition Discriminability (d′). Participants also completed a comprehensive neuropsychological battery, assessments of everyday functioning and experimental measures of SM. Results: CVLT-II SM impairment was significantly associated with increased errors on experimental SM measures and lower scores on measures of passage recall and executive functions, but not visuospatial skills. In a logistic regression controlling for clinicodemographic factors, CVLT-II SM impairment was a significant independent predictor of HAND, with the HAND + group showing higher rates of SM impairment than both the HAND − and HIV − groups. Finally, CVLT-II SM impairment was significantly related to a composite measure of everyday functioning, but this effect disappeared after adjusting for covariates. Note that, the overall pattern of findings across this study also held when CVLT-3 normative standards were applied to the SM indices. Conclusions: Results provide initial support for the construct and criterion validity of a CVLT-II SM index in the setting of HIV disease. Future studies should examine the validity of CVLT-II SM variables in other neuropsychological populations. [ABSTRACT FROM AUTHOR]

Objective Although medication management is a necessary daily activity for individuals with Huntington's disease (HD), medication management abilities and their relation to cognitive functioning have not been evaluated. Method Twenty individuals with HD and 20 healthy adults (HA) completed the Medication Management Abilities Assessment (MMAA). Individuals with HD also completed a self-report medication management measure and neuropsychological tests assessing executive function, retrospective memory, and prospective memory. Results Individuals with HD performed significantly poorer and made more undertaking errors on the MMAA as compared to HA. No group differences were found in overtaking errors. In the HD group, significant associations were found between undertaking errors and perceived medication management ability as well as between MMAA task performance and measures assessing prospective memory and executive functions. Conclusions Medication management capacity was negatively affected in individuals with HD and may be associated with difficulty remembering to take medications in the future. [ABSTRACT FROM AUTHOR]

Cross-species comparative studies have highlighted differences between human and mouse cystic fibrosis transmembrane conductance regulator (CFTR), the epithelial Cl- channel defective in cystic fibrosis (CF). Here, we compare the impact of the most common CF mutation F508del on the function of human and mouse CFTR heterologously expressed in mammalian cells and their response to CFTR modulators using the iodide efflux and patch-clamp techniques. Once delivered to the plasma membrane, human F508del-CFTR exhibited a severe gating defect characterized by infrequent channel openings and was thermally unstable, deactivating within minutes at 37°C. By contrast, the F508del mutation was without effect on the gating pattern of mouse CFTR, and channel activity demonstrated thermostability at 37°C. Strikingly, at all concentrations tested, the clinically approved CFTR potentiator ivacaftor was without effect on the mouse F508del-CFTR Cl- channel. Moreover, eight CFTR potentiators, including ivacaftor, failed to generate CFTR-mediated iodide efflux from CHO cells expressing mouse F508del-CFTR. However, they all produced CFTR-mediated iodide efflux with human F508del-CFTR-expressing CHO cells, while fifteen CFTR correctors rescued the plasma membrane expression of both human and mouse F508del-CFTR. Interestingly, the CFTR potentiator genistein enhanced CFTR-mediated iodide efflux from CHO cells expressing either human or mouse F508del-CFTR, whereas it only potentiated human F508del-CFTR Cl- channels in cell-free membrane patches, suggesting that its action on mouse F508del-CFTR is indirect. Thus, the F508del mutation has distinct effects on human and mouse CFTR Cl- channels. [ABSTRACT FROM AUTHOR]

The article focuses on demography of the sailors and officers who served in the Royal Navy that did so much to create the modern world during Queen Victoria's reign. It mentions geographical origin of ordinary sailors allotted pay to their families and the places and both stokers and seamen were concentrated in the south and south-east of England. It also mentions relationship between birthplace geography and commissioning port for royal yachts and tenders.

Age and HIV disease have additive effects on neural systems that support motor functioning. The current study examined the combined impact of aging and HIV on extrapyramidal motor functions, which were hypothesized to influence on activities of daily living (ADLs) and quality of life (QoL). Participants included 336 adults classified by HIV serostatus and age. A research nurse administered the Unified Parkinson's Disease Rating Scale (UPDRS) and participants completed the modified Lawton & Brody ADL and the Short Form Survey Instrument (SF-36) questionnaires as part of a larger neuropsychological research battery. A convenience subset of 172 participants completed a 14-month follow-up evaluation. At baseline, only older age was associated with mild extrapyramidal signs; however, at 14-month follow-up, independent adverse effects of both HIV status and age group were observed on a 3-level UPDRS change variable. Among older HIV+ adults, the presence of mild UPDRS motor signs was independently associated with basic and instrumental ADL dependence, as well as lower physical (ps <.05), but not mental QoL. In the modern treatment era, older HIV+ adults show higher frequency of mild extrapyramidal signs as compared to younger individuals (but not older HIV− persons) and are at higher risk of incident extrapyramidal signs relative to HIV− persons (but not younger HIV+ persons). When present in older HIV+ adults, extrapyramidal signs are of mild severity but nevertheless increase the risk of daily functioning problems and lower health-related physical QoL. [ABSTRACT FROM AUTHOR]

The increasing prevalence of older adults living with HIV has raised growing concerns about a possible rise in the incidence of neurocognitive disorders due to HIV and other age-related factors. In typical aging, subjective cognitive impairment (SCI) among individuals with normal neurocognitive functioning may be an early manifestation of an incipient neurocognitive disorder. The current study examined the frequency and correlates of SCI in 188 HIV-infected adults without performance-based neurocognitive deficits or a current psychiatric disorder and 133 HIV seronegative comparison participants. All participants completed the Prospective and Retrospective Memory Questionnaire and Profile of Mood States Confusion/Bewilderment scale. Consistent with the diagnostic criteria proposed by Jessen et al. (Alzheimers Dement 10(6):844-852, 2014), participants were classified with SCI if their scores on either of the self-reported measures was greater than 1.5 SD above the normative mean. A logistic regression controlling for current mood complaints and lifetime history of substance use disorders revealed that HIV infection increased the odds of SCI (odds ratio= 4.5 [1.6, 15.4], p = 0.004). Among HIV+ individuals, SCI was associated with lower performance-based learning and delayed memory scores (Cohen's d range 0.41-0.42.) and poorer global everyday functioning (odds ratio= 8.5 [2.6, 15.9]), but not HIV disease severity (ps > 0.10). In a sample of individuals without neurocognitive impairment or elevated mood symptoms, HIV disease was associated with a nearly fivefold increased odds of SCI compared to seronegative individuals, which may indicate an increased risk for developing major neurocognitive disorders as these HIV+ individuals age. [ABSTRACT FROM AUTHOR]

Among individuals living with HIV disease, approximately 60% experience problems with everyday functioning. The present study investigated the utility of the UCSD Performance-based Skills Assessment-Brief Version (UPSA-B) as a measure of functional capacity in HIV. We utilized a cross-sectional three-group design comparing individuals with HIV- associated neurocognitive disorder (HAND) (HIV + HAND+; n = 27), HIV+ neurocognitively normal individuals (HIV + HAND-; n = 51), and an HIV- comparison group (HIV-; n = 28) with broadly comparable demographics and non-HIV comorbidities. Participants were administered the UPSA-B, the Medication Management Test-Revised (MMT-R), and were assessed for manifest everyday functioning and quality of life, as part of a standardized clinical neurocognitive research battery. Results indicated that the HIV + HAND+ group had significantly lower UPSA-B scores than the HIV + HAND-group, but did not differ from the HIV- group. Among HIV+ individuals, UPSA-B scores were significantly related to MMT-R scores, all neurocognitive domains assessed, and education, but the UPSA-B was not related to manifest everyday functioning (e.g., unemployment), health-related quality of life, or HIV disease variables. Findings provide mixed support for the construct validity of the UPSA-B in HIV. Individuals impaired on the UPSA-B may be at increased risk for HAND, but the extent to which it detects general manifest everyday functioning problems is uncertain. [ABSTRACT FROM AUTHOR]

Ivacaftor is the first drug to target directly defects in the cystic fibrosis transmembrane conductance regulator (CFTR), which causes cystic fibrosis (CF). To understand better how ivacaftor potentiates CFTR channel gating, here we investigated the effects of temperature on its action. As a control, we studied the benzimidazolone UCCF-853, which potentiates CFTR by a different mechanism. Using the patch-clamp technique and cells expressing recombinant CFTR, we studied the single-channel behavior of wild-type and F508del-CFTR, the most common CF mutation. Raising the temperature of the intracellular solution from 23 to 37°C increased the frequency but reduced the duration of wild-type and F508del-CFTR channel openings. Although the open probability (Po) of wild-type CFTR increased progressively as temperature was elevated, the relationship between Po and temperature for F508del-CFTR was bell-shaped with a maximum Po at ~30°C. For wild-type CFTR and to a greatly reduced extent F508del-CFTR, the temperature dependence of channel gating was asymmetric with the opening rate demonstrating greater temperature sensitivity than the closing rate. At all temperatures tested, ivacaftor and UCCF-853 potentiated wild-type and F508del-CFTR. Strikingly, ivacaftor but not UCCF-853 abolished the asymmetric temperature dependence of CFTR channel gating. At all temperatures tested, Po values of wild-type CFTR in the presence of ivacaftor were approximately double those of F508del-CFTR, which were equivalent to or greater than those of wild-type CFTR at 37°C in the absence of the drug. We conclude that the principal effect of ivacaftor is to promote channel opening to abolish the temperature dependence of CFTR channel gating. [ABSTRACT FROM AUTHOR]

West Nile Virus (WNV) can be a neuroinvasive pathogen that may produce persistent mild-to-moderate neurocognitive impairments in some infected persons. Intra-individual variability (IIV) is an index of a person’s performance across a neuropsychological test or battery, which is an indicator of neurocognitive control and integrity of prefrontal systems. The present study examined possible associations of IIV to neurological health and well-being in WNV infection. Participants included 84 adults with a range of clinical WNV disease (31 West Nile Encephalitis, 16 West Nile Meningitis, 37 West Nile Fever) who completed the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). IIV was operationalized as covariance of variation (CoV), or the intra-individual standard deviation across 5 age-adjusted RBANS standard scores divided by the mean of standard scores. Participants were assessed for health-related quality of life (QoL) using the RAND 36-item short form health survey (SF-36). Analyses revealed that the West Nile Encephalitis group had higher neurocognitive CoV compared to the West Nile Fever group, and this difference was associated with a medium effect size (Cohen’s d = .52). Mixed linear models controlling for estimated IQ, activities of daily living, depression, neuroinvasive disease groups, and fatigue showed that higher RBANS CoV was associated with lower physical, but not mental health QoL. In persons with WNV infection, there is a modest association between elevations in IIV and encephalitis, and even subtle disruptions in neuropsychological functioning show relationships with important self-reported functioning as measured by physical health quality of life. Future studies should examine whether IIV predicts long-term health outcomes (e.g., mortality) in individuals infected with WNV. [ABSTRACT FROM AUTHOR]

Objective: Prospective memory (PM) is described as the capacity to form and maintain an intention that is executed in response to a specific cue. Neural injury and associated neurocognitive disorders are common among persons living with HIV disease, who might therefore be susceptible to impairment in PM. Method: This literature review utilized a structured qualitative approach to summarize and evaluate our current understanding of PM functioning in people living with HIV disease. 33 studies of PM in HIV+ persons met criteria for inclusion. Results: Findings showed that HIV is associated with moderate deficits in PM, which appear to be largely independent of commonly observed comorbid factors. The pattern of PM deficits reveals dysregulation of strategic processes that is consistent with the frontal systems pathology and associated executive dysfunction that characterizes HIV-associated neural injury. The literature also suggests that HIV-associated PM deficits present a strong risk of concurrent problems in a wide range of health behaviors (e.g. medication non-adherence) and activities of daily living (e.g. employment). Early attempts to improve PM in HIV disease have revealed that supporting strategic processes might be effective for some individuals. Conclusions: HIV-associated PM deficits are common and exert a significant adverse effect on the daily lives and health of infected persons. Much work remains to be done to understand the cognitive architecture of HIV-associated PM deficits and the most efficient means to enhance PM functioning and improve health outcomes in persons living with HIV. [ABSTRACT FROM AUTHOR]

Background and Purpose: Rescue of F508del-cystic fibrosis (CF) transmembrane conductance regulator (CFTR), the most common CF mutation, requires small molecules that overcome protein processing, stability and channel gating defects. Here, we investigate F508del-CFTR rescue by CFFT-004, a small molecule designed to independently correct protein processing and channel gating defects.Experimental Approach: Using CFTR-expressing recombinant cells and CF patient-derived bronchial epithelial cells, we studied CFTR expression by Western blotting and channel gating and stability with the patch-clamp and Ussing chamber techniques.Key Results: Chronic treatment with CFFT-004 improved modestly F508del-CFTR processing, but not its plasma membrane stability. By contrast, CFFT-004 rescued F508del-CFTR channel gating better than C18, an analogue of the clinically used CFTR corrector lumacaftor. Subsequent acute addition of CFFT-004, but not C18, potentiated F508del-CFTR channel gating. However, CFFT-004 was without effect on A561E-CFTR, a CF mutation with a comparable mechanism of CFTR dysfunction as F508del-CFTR. To investigate the mechanism of action of CFFT-004, we used F508del-CFTR revertant mutations. Potentiation by CFFT-004 was unaffected by revertant mutations, but correction was abolished by the revertant mutation G550E. These data suggest that correction, but not potentiation, by CFFT-004 might involve nucleotide-binding domain 1 of CFTR.Conclusions and Implications: CFFT-004 is a dual-acting small molecule with independent corrector and potentiator activities that partially rescues F508del-CFTR in recombinant cells and native airway epithelia. The limited efficacy and potency of CFFT-004 suggests that combinations of small molecules targeting different defects in F508del-CFTR might be a more effective therapeutic strategy than a single agent. [ABSTRACT FROM AUTHOR]

HIV-associated neurocognitive disorders (HAND) occur in approximately 50% of HIV-infected individuals, yet available diagnostic criteria yield varying prevalence rates. This study examined the frequency, reliability, and sensitivity to everyday functioning problems of three HAND diagnostic criteria (DSM-5, Frascati, Gisslén). Participants included 361 adults with HIV disease and 199 seronegative adults. Neurocognitive status as defined by each of the three diagnostic systems was determined via a comprehensive neuropsychological battery. Everyday functioning was evaluated through self-report and clinician ratings. Results of logistic regressions revealed an association of HIV serostatus with Frascati-defined neurocognitive impairment ( p = .027, OR = 1.7[1.1, 2.7]), but not DSM-5 or Gisslén-defined criteria ( ps > .05). Frascati and DSM-5 criteria demonstrated agreement on 71% of observations, Frascati and Gisslén showed agreement on 80%, and DSM-5 and Gisslén criteria showed agreement on 46%, though reliability across the three criteria was poor. Only Frascati-defined neurocognitive impairment significantly predicted everyday functioning problems ( p = .002, OR = 2.3[1.4, 3.8]). However, when both neurocognitive and complaint criteria were considered, the DSM-5 guidelines demonstrated significant relationships to everyday functioning, serostatus, and also increased reliability overtime compared to neurocognitive criteria alone (all ps < .05). A subset ( n = 118) of the HIV+ group was assessed again after 14.0 (2.2) months. DSM-5 criteria evidenced significantly higher rates of incident neurocognitive disorder compared to both Frascati ( p = .003) and Gisslén ( p = .021) guidelines, while there were fewer remitting neurocognitive disorder diagnoses when Gisslén criteria were applied to the study sample compared to Frascati ( p = .04). Future studies should aim to identify gold standard biological markers (e.g., neuropathology) and clinical outcomes associated with specific diagnostic criteria. [ABSTRACT FROM AUTHOR]

There is debate as to whether the neurocognitive changes associated with HIV infection represent an acceleration of the typical aging process or more simply reflect a greater accentuated risk for age-related declines. We aimed to determine whether accelerated neurocognitive aging is observable in a sample of older HIV-infected individuals compared to age-matched seronegatives and older old (i.e., aged ≥65) seronegative adults. Participants in a cross-sectional design included 48 HIV-seronegative (O−) and 40 HIV-positive (O+) participants between the ages of 50-65 (mean ages = 55 and 56, respectively) and 40 HIV-seronegative participants aged ≥65 (OO−; mean age = 74) who were comparable for other demographics. All participants were administered a brief neurocognitive battery of attention, episodic memory, speeded executive functions, and confrontation naming (i.e., Boston Naming Test). The O+ group performed more poorly than the O− group (i.e., accentuated aging), but not differently from the OO− on digit span and initial recall of a supraspan word list, consistent with an accelerating aging profile. However, the O+ group's performance was comparable to the O− group on all other neurocognitive tests ( ps > 0.05). These data partially support a model of accelerated neurocognitive aging in HIV infection, which was observed in the domain of auditory verbal attention, but not in the areas of memory, language, or speeded executive functions. Future studies should examine whether HIV-infected adults over 65 evidence accelerated aging in downstream neurocognitive domains and subsequent everyday functioning outcomes. [ABSTRACT FROM AUTHOR]

Synonymous single nucleotide polymorphisms (sSNPs) are considered neutral for protein function, as by definition they exchange only codons, not amino acids. We identified an sSNP that modifies the local translation speed of the cystic fibrosis transmembrane conductance regulator (CFTR), leading to detrimental changes to protein stability and function. This sSNP introduces a codon pairing to a low-abundance tRNA that is particularly rare in human bronchial epithelia, but not in other human tissues, suggesting tissue-specific effects of this sSNP. Up-regulation of the tRNA cognate to the mutated codon counteracts the effects of the sSNP and rescues protein conformation and function. Our results highlight the wide-ranging impact of sSNPs, which invert the programmed local speed of mRNA translation and provide direct evidence for the central role of cellular tRNA levels in mediating the actions of sSNPs in a tissue-specific manner. [ABSTRACT FROM AUTHOR]

One important limitation of prior studies examining functional decline in Huntington’s disease (HD) has been the reliance on self-reported measures of ability. Since report-based methods can be biased by lack of insight, depression, and cognitive impairment, contrasting self-reported ability with measures that assess capacity may lead to a more comprehensive estimation of real-world functioning. The present study examined self-reported ability to perform instrumental activities of daily living (iADLs) and performance-based financial management capacity in 20 patients diagnosed with mild-moderate Huntington’s disease (HD) and 20 demographically similar healthy adults. HD patients reported significantly greater declines in their ability to manage finances. On the capacity measure of financial management, HD patients performed significantly below healthy adults. Additionally, in the HD group there were no significant correlations between self-reported ability and capacity measures of financial management. HD patients endorsed declines in global iADL ability and exhibited deficits in functional capacity when performing a financial management task. Capacity measures may aid in assessing the extent to which HD patients accurately estimate real-world iADL performance, and the present findings suggest that such measures of capacity may be related to the cognitive, but not motor or affective, symptoms of HD. [ABSTRACT FROM PUBLISHER]

Objectives: Episodic memory deficits are both common and impactful among persons infected with HIV; however, we know little about how to improve such deficits in the laboratory or in real life. Retrieval practice, by which retrieval of newly learned material improves subsequent recall more than simple restudy, is a robust memory boosting strategy that is effective in both healthy and clinical populations. In this study, we investigated the benefits of retrieval practice in 52 people living with HIV and 21 seronegatives. Methods: In a within-subjects design, all participants studied 48 verbal paired associates in 3 learning conditions: Massed-Restudy, Spaced-Restudy, and Spaced-Testing. Retention of verbal paired associates was assessed after short- (30 min) and long- (30 days) delay intervals. Results: After a short delay, both HIV+ persons and seronegatives benefited from retrieval practice more so than massed and spaced restudy. The same pattern of results was observed specifically for HIV+ persons with clinical levels of memory impairment. The long-term retention interval data evidenced a floor effect that precluded further analysis. Conclusions: This study provides evidence that retrieval practice improves verbal episodic memory more than some other mnemonic strategies among HIV+ persons. (JINS, 2017, 23, 214–222) [ABSTRACT FROM AUTHOR]

In cystic fibrosis, ion-transport abnormalities cause problems in many organs. A small molecule that forms cell-membrane pores allowing ion transport shows therapeutic promise in human cells and a model of the disease.A natural molecule that facilitates ion transport aids lung function. [ABSTRACT FROM AUTHOR]

Key points The cystic fibrosis transmembrane conductance regulator (CFTR), which is defective in the genetic disease cystic fibrosis (CF), forms a gated pathway for chloride movement regulated by intracellular ATP., To understand better CFTR function, we investigated the regulation of channel openings by intracellular pH., We found that short-lived channel closures during channel openings represent subtle changes in the structure of CFTR that are regulated by intracellular pH, in part, at ATP-binding site 1 formed by the nucleotide-binding domains., Our results provide a framework for future studies to understand better the regulation of channel openings, the dysfunction of CFTR in CF and the action of drugs that repair CFTR gating defects., Abstract Cystic fibrosis transmembrane conductance regulator (CFTR) is an ATP-gated Cl− channel defective in the genetic disease cystic fibrosis (CF). The gating behaviour of CFTR is characterized by bursts of channel openings interrupted by brief, flickery closures, separated by long closures between bursts. Entry to and exit from an open burst is controlled by the interaction of ATP with two ATP-binding sites, sites 1 and 2, in CFTR. To understand better the kinetic basis of CFTR intraburst gating, we investigated the single-channel activity of human CFTR at different intracellular pH (pHi) values. When compared with the control (pHi 7.3), acidifying pHi to 6.3 or alkalinizing pHi to 8.3 and 8.8 caused small reductions in the open-time constant (τo) of wild-type CFTR. By contrast, the fast closed-time constant (τcf), which describes the short-lived closures that interrupt open bursts, was greatly increased at pHi 5.8 and 6.3. To analyse intraburst kinetics, we used linear three-state gating schemes. All data were satisfactorily modelled by the C1 ↔ O ↔ C2 kinetic scheme. Changing the intracellular ATP concentration was without effect on τo, τcf and their responses to pHi changes. However, mutations that disrupt the interaction of ATP with ATP-binding site 1, including K464A, D572N and the CF-associated mutation G1349D all abolished the prolongation of τcf at pHi 6.3. Taken together, our data suggest that the regulation of CFTR intraburst gating is distinct from the ATP-dependent mechanism that controls channel opening and closing. However, our data also suggest that ATP-binding site 1 modulates intraburst gating. [ABSTRACT FROM AUTHOR]

Objective: HIV is associated with frontostriatal dysregulation and executive dysfunction. This study evaluated whether HIV-infected individuals evidence deficits in random number generation (RNG), which is a strategic task requiring paced, rule-guided production of digits. Method: In total, 74 HIV+ adults and 54 seronegative comparison participants completed a comprehensive research neuropsychological battery. Participants produced a random digit sequence by avoiding any order and using numbers 1 through 10 for 100 s at a pace of 1 digit/s. Outcomes included intrusions, repetitions, seriation (1-2-3-4), and cycling (median length of gaps between repeating digits). Results: HIV disease was associated with higher levels of seriation and cycling (ps < .05) but not intrusions or repetitions (ps > .10). Among HIV+ individuals, higher seriation was associated with neuropsychological performance including poorer auditory attention, verbal learning, and delayed memory, whereas higher cycling scores were associated with poorer delayed memory and verbal fluency (ps < .05). Higher seriation also was independently associated with self-reported declines in activities of daily living (ADLs) in the HIV+ group. Conclusions: Individuals living with HIV disease evidence moderate difficulties in inhibiting statistically unlikely non-random sequences, which showed medium associations with higher order verbal abilities and may contribute to greater declines in everyday functioning outcomes. Future studies might examine RNG's role in health behaviors such as medical decision-making or medication adherence. [ABSTRACT FROM AUTHOR]

The current study examined the individual and combined effects of age and HIV serostatus on anxiety symptoms and diagnoses among a community sample. Participants included 163 Older (50+ years) HIV+ persons, 113 Younger (<40) HIV+ persons, 95 Older HIV- persons, and 75 Younger HIV- persons who completed the Profile of Mood States and the Composite International Diagnostic Interview as part of a baseline neuroAIDS research assessment. Results showed that HIV infection was associated with significantly higher rates of anxiety symptoms as well as 12-month and lifetime diagnoses of Generalized Anxiety Disorder (GAD) and Panic Disorder (PD). There was no significant effect of age and no significant interaction between HIV serostatus and age; however, Older HIV+ participants were significantly older at onset of anxiety diagnoses as compared to their Younger HIV+ counterparts. Among both Older and Younger HIV+ participants, there were high rates of comorbidity between anxiety disorders and Major Depressive and methamphetamine use disorders. Across the lifespan, HIV-associated neurocognitive disorders interacted with 12-month anxiety disorders to increase risk of poorer everyday functioning outcomes. Overall, these data suggest that HIV disease and its comorbidities are related to elevated anxiety symptoms and diagnoses in both younger and older adults. [ABSTRACT FROM PUBLISHER]

Dictionary methods have proved very useful in compressive sensing. Herein we show that, for dictionaries to represent the point spread functions (PSFs) of image formation in atmospheric turbulence, it is possible to construct dictionaries computationally. Computationally created dictionaries make unnecessary the exhaustive collection of PSF data, for arbitrarily large numbers of conditions of turbulence and optical image formation systems, while also reducing the overall number of dictionaries that need to be created and stored. [ABSTRACT FROM AUTHOR]