A pilot study of cognition and creativity among persons with HIV disease referred for neuropsychological evaluation.

Creativity can help people to innovate, overcome obstacles, and successfully navigate challenges in daily life. Some aspects of creativity rely on the prefrontostriatal loops and executive functions, which can be compromised in persons with HIV (PWH). This pilot study examined whether neuropsychological functioning plays a role in creativity in PWH. A consecutive series of 41 PWH who were referred to an urban neuropsychology clinic in southeastern Texas were enrolled. Participants completed the Abbreviated Torrance Test for Adults (ATTA) to measure creativity, from which standardized creativity scores of fluency, originality, elaboration, and flexibility were derived. Participants also completed several measures of everyday functioning and a brief clinical neuropsychological battery measuring executive functions, motor skills, memory, and visuoconstruction. Global neuropsychological functioning showed a large, positive association with ATTA creativity performance that did not vary meaningfully by creativity domain and was independent of premorbid IQ. ATTA creativity scores were not associated with any measure of everyday functioning. Findings from this pilot study suggest that higher levels of neuropsychological functioning may support multiple dimensions of creativity in adults with HIV disease. Future studies might examine whether creativity moderates the association between HIV-associated neurocognitive impairment and various health behaviors (e.g., adherence, appointment attendance).

Expression of a Truncated Form of ODAD1 Associated with an Unusually Mild Primary Ciliary Dyskinesia Phenotype.

Primary ciliary dyskinesia (PCD) is a rare lung disease caused by mutations that impair the function of motile cilia, resulting in chronic upper and lower respiratory disease, reduced fertility, and a high prevalence of situs abnormalities. The disease is genetically and phenotypically heterogeneous, with causative mutations in > 50 genes identified, and clinical phenotypes ranging from mild to severe. Absence of ODAD1 (CCDC114), a component of the outer dynein arm docking complex, results in a failure to assemble outer dynein arms (ODAs), mostly immotile cilia, and a typical PCD phenotype. We identified a female (now 34 years old) with an unusually mild clinical phenotype who has a homozygous non-canonical splice mutation (c.1502+5G>A) in ODAD1. To investigate the mechanism for the unusual phenotype, we performed molecular and functional studies of cultured nasal epithelial cells. We demonstrate that this splice mutation results in the expression of a truncated protein that is attached to the axoneme, indicating that the mutant protein retains partial function. This allows for the assembly of some ODAs and a significant level of ciliary activity that may result in the atypically mild clinical phenotype. The results also suggest that partial restoration of ciliary function by therapeutic agents could lead to significant improvement of disease symptoms.

Clinical identification of psychogenic nonepileptic events using combinations of psychological tests in a veteran sample.

OBJECTIVE: Patients with psychogenic nonepileptic events (PNEE) exhibit heterogenous symptoms and are best diagnosed with long-term video-electroencephalogram (vEEG) data. While extensive univariate data suggest psychological tests may confirm the etiology of PNEE, the multivariate discriminant utility of psychological tests is less clear. The current study aggregated likelihood ratios of multiple psychological tests to evaluate incremental and discriminant utility for PNEE. METHODS: Veterans with vEEG-diagnosed PNEE (n = 166) or epileptic seizures (n = 92) completed self-report measures and brief neuropsychological evaluations during the 4-day vEEG hospitalization. Receiver operating characteristic (ROC) curves identified discriminating psychological tests and corresponding cut-scores (0.85 minimum specificity). Likelihood ratios from the remaining cut-scores were sequentially linked using the sample base rate of PNEE (64%) and alternative base rates (10%, 20%, 30%, 40%) to estimate posttest probabilities (PTP) of test combinations. RESULTS: The Health Attitudes Survey, Health History Checklist, and Minnesota Multiphasic Personality Inventory-2-Restructured Form scales FBS-r, RC1, MLS, and NUC were identified as discriminating indicators of PNEE. Average PTPs were ≥90% when three or more indicators out of six administered were present at the sample base rate. Regardless of PNEE base rate, PTP for PNEE was ≥98% when all discriminating indicators were present and 92-99% when five of six indicators administered were present. PTPs were largely consistent with observed positive predictive values, particularly as indicators present increased. SIGNIFICANCE: Aggregating psychological tests identified PNEE with a high degree of accuracy, regardless of PNEE base rate. Combining psychological tests may be useful for confirming the etiology of PNEE.

Primary Ciliary Dyskinesia: Longitudinal Study of Lung Disease by Ultrastructure Defect and Genotype.

RATIONALE: In primary ciliary dyskinesia, factors leading to disease heterogeneity are poorly understood. OBJECTIVES: To describe early lung disease progression in primary ciliary dyskinesia and identify associations between ultrastructural defects and genotypes with clinical phenotype. METHODS: This was a prospective, longitudinal (5 yr), multicenter, observational study. Inclusion criteria were less than 19 years at enrollment and greater than or equal to two annual study visits. Linear mixed effects models including random slope and random intercept were used to evaluate longitudinal associations between the ciliary defect group (or genotype group) and clinical features (percent predicted FEV1 and weight and height z-scores). MEASUREMENTS AND MAIN RESULTS: A total of 137 participants completed 732 visits. The group with absent inner dynein arm, central apparatus defects, and microtubular disorganization (IDA/CA/MTD) (n = 41) were significantly younger at diagnosis and in mixed effects models had significantly lower percent predicted FEV1 and weight and height z-scores than the isolated outer dynein arm defect (n = 55) group. Participants with CCDC39 or CCDC40 mutations (n = 34) had lower percent predicted FEV1 and weight and height z-scores than those with DNAH5 mutations (n = 36). For the entire cohort, percent predicted FEV1 decline was heterogeneous with a mean (SE) decline of 0.57 (0.25) percent predicted/yr. Rate of decline was different from zero only in the IDA/MTD/CA group (mean [SE], -1.11 [0.48] percent predicted/yr; P = 0.02). CONCLUSIONS: Participants with IDA/MTD/CA defects, which included individuals with CCDC39 or CCDC40 mutations, had worse lung function and growth indices compared with those with outer dynein arm defects and DNAH5 mutations, respectively. The only group with a significant lung function decline over time were participants with IDA/MTD/CA defects.

Lower Neurocognitive Functioning Disrupts the Effective Use of Internet-Based Health Resources in HIV Disease: The Mediating Effects of General Health Literacy Capacity.

HIV-associated neurocognitive impairment is an independent predictor of low general health literacy, which can be associated with poor disease outcomes (e.g., viremia). Given the increasing frequency with which health behaviors occur in an online environment (e.g., health information seeking, provider interactions), there is a specific need to understand the predictors of electronic health (eHealth) literacy of persons living with HIV disease. In this study, 90 HIV+ persons completed the eHealth Literacy Scale (eHEALS), which measures one's awareness, skills and evaluation of online health resources. Participants also completed a comprehensive battery of clinical neurocognitive tests and well-validated performance-based measures of general health literacy capacity (e.g., knowledge, numeracy). Results showed that, independent of education, lower neurocognitive function was moderately related to lower eHEALS scores, particularly in the domains of learning and motor skills. Of particular note, general health literacy capacity emerged as a significant mediator of the relationship between neurocognition and eHealth literacy. Thus, the adverse effects of neurocognition on health literacy capacity carries a downstream adverse influence on HIV+ persons' awareness, skills, and evaluation of health-related resources in the online environment.

Adjunct Aripiprazole Reduces Prolactin and Prolactin-Related Adverse Effects in Premenopausal Women With Psychosis: Results From the DAAMSEL Clinical Trial.

PURPOSE/BACKGROUND: Prolactin-related adverse effects contribute to nonadherence and adverse health consequences, particularly in women with severe mental illness. Treating these adverse effects may improve treatment acceptability, adherence, and long-term outcomes. METHODS/PROCEDURES: Premenopausal women with a Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision diagnosis of schizophrenia, schizoaffective disorder, or bipolar disorder were recruited for a randomized, double-blind, placebo-controlled 16-week trial of adjunct aripiprazole (5-15 mg/d). Participants had elevated prolactin (>24 ng/mL) and were experiencing galactorrhea, amenorrhea, oligomenorrhea, or sexual dysfunction on a prolactin-elevating antipsychotic. Participants were evaluated biweekly for prolactin elevation and galactorrhea and completed a menstrual diary review. Psychiatric symptoms and adverse effects were closely monitored. FINDINGS/RESULTS: Forty-six women were randomized (n = 25 aripiprazole, n = 21 placebo). Thirty-seven completed at least 8 weeks of the study (n = 20 [80%] aripiprazole and n = 17 [81%] placebo). Aripiprazole (mean dose, 11.7 ± 2.4 mg/d) was effective for lowering prolactin relative to placebo (P = 0.04). In addition, 45% (9/20) of the aripiprazole group had a normalized prolactin (<24 mg/mL) compared with 12% (2/17) of the placebo group (P = 0.028). Galactorrhea resolved in 77% (10/13) of the aripiprazole-treated participants compared with 33% (4/12) in the placebo group (P = 0.028). Normalization of sexual function (<16 on the Arizona Sexual Experience Scale) occurred in 50% on aripiprazole (7/14) versus 9% (1/11) on placebo (P = 0.030). No differences between groups in symptoms or adverse effects were noted. Overall, women rated a mean score of 4.6 ± 0.6 on a 5-point Likert scale for sexual function improvement, suggesting their particular satisfaction with improvement in this domain. IMPLICATIONS/CONCLUSIONS: Building upon prior studies, this rigorous evaluation confirms the utility of adjunctive aripiprazole as a strategy for improving prolactin and managing prolactin-related adverse effects in premenopausal women with psychosis.

Adjunctive Minocycline in Clozapine-Treated Patients with Schizophrenia: Analyzing the Effects of Minocycline on Clozapine Plasma Levels.

Clozapine is the sole antipsychotic agent effective for the treatment of refractory schizophrenia. Sixty percent of clozapine-treated patients, however, fail to adequately respond. Minocycline, a tetracycline antibiotic, possesses antiinflammatory and neuroprotective properties that may play a role in schizophrenia. Clozapine is mainly metabolized by CYP1A2 enzymes, and minocycline may potentially inhibit CYP1A2 as hypothesized by case report data. To date, no pharmacokinetic interaction has been reported between minocycline and clozapine. This is a secondary analysis of a 10-week controlled study of adjunctive minocycline to clozapine in treatment refractory schizophrenia. Clozapine plasma levels were collected every two weeks during the study. 28 participants assigned to receive minocycline and 22 assigned to placebo were included. No differences existed in baseline demographics, clozapine dose or plasma levels. Average changes from baseline in clozapine plasma level (p = 0.033) were significantly higher in the minocycline group despite maintenance of stable doses. No statistically significant treatment differences were found in the norclozapine (p = 0.754) or total clozapine (p = 0.053) changes in plasma levels, although possible changes in total clozapine levels require further investigation. This analysis suggests that minocycline administration may lead to increased clozapine plasma levels. Further study is needed to examine possible explanations.

Volunteer navigation partnerships: Piloting a compassionate community approach to early palliative care.

BACKGROUND: A compassionate community approach to palliative care provides important rationale for building community-based hospice volunteer capacity. In this project, we piloted one such capacity-building model in which volunteers and a nurse partnered to provide navigation support beginning in the early palliative phase for adults living in community. The goal was to improve quality of life by developing independence, engagement, and community connections. METHODS: Volunteers received navigation training through a three-day workshop and then conducted in-home visits with clients living with advanced chronic illness over one year. A nurse navigator provided education and mentorship. Mixed method evaluation data was collected from clients, volunteer navigators, the nurse navigator, and other stakeholders. RESULTS: Seven volunteers were partnered with 18 clients. Over the one-year pilot, the volunteer navigators conducted visits in home or by phone every two to three weeks. Volunteers were skilled and resourceful in building connections and facilitating engagement. Although it took time to learn the navigator role, volunteers felt well-prepared and found the role satisfying and meaningful. Clients and family rated the service as highly important to their care because of how the volunteer helped to make the difficult experiences of aging and advanced chronic illness more livable. Significant benefits cited by clients were making good decisions for both now and in the future; having a surrogate social safety net; supporting engagement with life; and ultimately, transforming the experience of living with illness. Overall the program was perceived to be well-designed by stakeholders and meeting an important need in the community. Sustainability, however, was a concern expressed by both clients and volunteers. CONCLUSIONS: Volunteers providing supportive navigation services during the early phase of palliative care is a feasible way to foster a compassionate community approach to care for an aging population. The program is now being implemented by hospice societies in diverse communities across Canada.

Blood Pressure and Heart Rate Changes During Clozapine Treatment.

People with schizophrenia are 3-4 times more likely to die from cardiovascular disease than the general population. Clozapine (CLZ) is the gold standard of treatment for refractory schizophrenia. It has been associated with tachycardia and recent evidence shows individuals prescribed CLZ may develop blood pressure (BP) elevation and hypertension. The purpose of this study was to examine the effects of CLZ on BP and heart rate (HR). This was a retrospective chart review of patients 18-75 years old with a DSM IV diagnosis of Schizophrenia or Schizoaffective disorder. Primary outcomes were systolic blood pressure (SBP), diastolic blood pressure (DBP), and HR measured 12 weeks before and 24 weeks during CLZ treatment. Eighteen patient records were included in this study. The mean stabilized CLZ dose was 441.7 ± 171.8 mg/day. DBP (t = 1.02, df = 79.5, = 2.00, 0.049) and HR (t = 1.32, df = 355  = -4.61, < 0.0001) were significantly higher after CLZ initiation. A trend was noted for increase in SBP (p = 0.071). 22 % of patients met criteria for hypertension before CLZ and 67 % during CLZ treatment (Chi Square = 6.25, df = 1, p = 0.0124). No significant changes in weight or renal function occured during CLZ treatment. No patients had evidence of cardiomyopathy. The data suggest CLZ may be associated with a rise in BP and HR. The results of this study support previous literature that found an increase in SBP/DBP regardless of CLZ dose, occurring early in treatment. Due to high risk of cardiovascular morbidity and mortality, more work is needed to determine risk factors and understand the mechanism of action that may cause this side effect.

Adjunctive Minocycline in Clozapine-Treated Schizophrenia Patients With Persistent Symptoms.

OBJECTIVE: Clozapine is the most effective antipsychotic for treatment refractory people with schizophrenia, yet many patients only partially respond. Accumulating preclinical and clinical data suggest benefits with minocycline. We tested adjunct minocycline to clozapine in a 10-week, double-blind, placebo-controlled trial. Primary outcomes tested were positive, and cognitive symptoms, while avolition, anxiety/depression, and negative symptoms were secondary outcomes. METHODS: Schizophrenia and schizoaffective participants (n = 52) with persistent positive symptoms were randomized to receive adjunct minocycline (100 mg oral capsule twice daily; n = 29) or placebo (n = 23). RESULTS: Brief Psychiatric Rating Scale (BPRS) psychosis factor (P = 0.098; effect size [ES], 0.39) and BPRS total score (P = 0.075; ES, 0.55) were not significant. A change in total BPRS symptoms of more than or equal to 30% was observed in 7 (25%) of 28 among minocycline and 1 (4%) of 23 among placebo participants, respectively (P = 0.044). Global cognitive function (MATRICS Consensus Cognitive Battery) did not differ, although there was a significant variation in size of treatment effects among cognitive domains (P = 0.03), with significant improvement in working memory favoring minocycline (P = 0.023; ES, 0.41). The Scale for the Assessment of Negative Symptoms total score did not differ, but significant improvement in avolition with minocycline was noted (P = 0.012; ES, 0.34). Significant improvement in the BPRS anxiety/depression factor was observed with minocycline (P = 0.028; ES, 0.49). Minocycline was well tolerated with significantly fewer headaches and constipation compared with placebo. CONCLUSIONS: Minocycline's effect on the MATRICS Consensus Cognitive Battery composite score and positive symptoms were not statistically significant. Significant improvements with minocycline were seen in working memory, avolition, and anxiety/depressive symptoms in a chronic population with persistent symptoms. Larger studies are needed to validate these findings.

Compensatory Strategy Intervention: What Older Patients Want and Why.

OBJECTIVE: Compensatory strategies can improve performance of instrumental activities of daily living in people with cognitive impairment. This study investigated patient interest in compensatory strategy interventions and preference for various intervention formats. METHODS: Semi-structured qualitative interviews with 38 older adults with cognitive impairment queried motivation to improve strategy use and interest in intervention formats/delivery methods. Two coders used thematic analysis to determine rates of interest in each intervention type and explore patient-reported barriers and facilitators to motivation and intervention models. RESULTS: Most of the samples reported motivation to enhance compensatory strategy use. Degree of motivation was driven by current experiences with strategy use, perceived benefit of potential changes, intrinsic desire to improve life and self, and current perceived need. The vast majority were interested in hour-long, multi-session, instructor-led interventions. Just over half of the sample was interested in a self-directed virtual program, and just under half was interested in involving family/friends. Facilitators and barriers to interest in intervention formats and delivery methods varied based on participants' previous experiences, preferred learning style, content, and time commitment of the intervention, and perceived current need for intervention. One-fifth of the sample expressed no interest in any intervention type, though they expressed openness to assistance in the future as needed. CONCLUSIONS: Older adults with cognitive impairment are generally motivated to enhance their compensatory strategy use. Clinicians/researchers designing compensatory strategy interventions should consider instructor-led formats, present individualized benefits of interventions, and demonstrate the benefits of both preventative and remedial intervention to optimize patient engagement.

Treating symptomatic hyperprolactinemia in women with schizophrenia: presentation of the ongoing DAAMSEL clinical trial (Dopamine partial Agonist, Aripiprazole, for the Management of Symptomatic ELevated prolactin).

Prolactin elevations occur in people treated with antipsychotic medications and are often much higher in women than in men. Hyperprolactinemia is known to cause amenorrhea, oligomenorrhea, galactorrhea and gynecomastia in females and is also associated with sexual dysfunction and bone loss. These side effects increase risk of antipsychotic nonadherence and suicide and pose significant problems in the long term management of women with schizophrenia. In this manuscript, we review the literature on prolactin; its physiology, plasma levels, side effects and strategies for treatment. We also present the rationale and protocol for an ongoing clinical trial to treat symptomatic hyperprolactinemia in premenopausal women with schizophrenia. More attention and focus are needed to address these significant side effects and help the field better personalize the treatment of women with schizophrenia.

Lack of both bradykinin B1 and B2 receptors enhances nephropathy, neuropathy, and bone mineral loss in Akita diabetic mice.

An insertion polymorphism of the angiotensin-I converting enzyme gene (ACE) is common in humans and the higher expressing allele is associated with an increased risk of diabetic complications. The ACE polymorphism does not significantly affect blood pressure or angiotensin II levels, suggesting that the kallikrein-kinin system partly mediates the effects of the polymorphism. We have therefore explored the influence of lack of both bradykinin receptors (B1R and B2R) on diabetic nephropathy, neuropathy, and osteopathy in male mice heterozygous for the Akita diabetogenic mutation in the insulin 2 gene (Ins2). We find that all of the detrimental phenotypes observed in Akita diabetes are enhanced by lack of both B1R and B2R, including urinary albumin excretion, glomerulosclerosis, glomerular basement membrane thickening, mitochondrial DNA deletions, reduction of nerve conduction velocities and of heat sensation, and bone mineral loss. Absence of the bradykinin receptors also enhances the diabetes-associated increases in plasma thiobarbituric acid-reactive substances, mitochondrial DNA deletions, and renal expression of fibrogenic genes, including transforming growth factor beta1, connective tissue growth factor, and endothelin-1. Thus, lack of B1R and B2R exacerbates diabetic complications. The enhanced renal injury in diabetic mice caused by lack of B1R and B2R may be mediated by a combination of increases in oxidative stress, mitochondrial DNA damage and over expression of fibrogenic genes.

Airway Inflammation in Children with Primary Ciliary Dyskinesia.

Rationale: The role of airway inflammation in disease pathogenesis in children with primary ciliary dyskinesia (PCD) is poorly understood. Objectives: We investigated relationships between sputum inflammation measurements, age, lung function, bronchiectasis, airway infection, and ultrastructural defects in children with PCD. Methods: Spontaneously expectorated sputum was collected from clinically stable children and adolescents with PCD ages 6 years and older participating in a multicenter, observational study. Sputum protease and inflammatory cytokine concentrations were correlated with age, lung function, and chest computed tomography measures of structural lung disease, whereas differences in concentrations were compared between ultrastructural defect categories and between those with and without detectable bacterial infection. Results: Sputum from 77 children with PCD (39 females [51%]; mean [standard deviation] age, 13.9 [4.9] yr; mean [standard deviation] forced expiratory volume in 1 second [FEV1]% predicted, 80.8 [20.5]) was analyzed. Sputum inflammatory marker measurements, including neutrophil elastase activity, IL-1ß (interleukin-1ß), IL-8, and TNF-α (tumor necrosis factor α) concentrations, correlated positively with age, percentage of bronchiectasis, and percentage of total structural lung disease on computed tomography, and negatively with lung function. Correlations between neutrophil elastase concentrations and FEV1% predicted and percentage of bronchiectasis were -0.32 (95% confidence interval, -0.51 to -0.10) and 0.46 (0.14 to 0.69), respectively. Sputum neutrophil elastase, IL-1ß, and TNF-α concentrations were higher in those with detectable bacterial pathogens. Participants with absent inner dynein arm and microtubular disorganization had similar inflammatory profiles compared with participants with outer dynein arm defects. Conclusions: In this multicenter pediatric PCD cohort, elevated concentrations of sputum proteases and cytokines were associated with impaired lung function and structural damage as determined by chest computed tomography, suggesting that sputum inflammatory measurements could serve as biomarkers in PCD.

Laterality Defects in Primary Ciliary Dyskinesia: Relationship to Ultrastructural Defect or Genotype.

Rationale: The association between organ laterality abnormalities and ciliary ultrastructural defect or genotype in primary ciliary dyskinesia is poorly understood. Objectives: To determine if there is an association between presence and/or type of laterality abnormality and ciliary ultrastructural defect or genotype. Methods: Participants with primary ciliary dyskinesia in a multicenter, prospective study were grouped based on ciliary ultrastructural defect or genotype. In a retrospective analysis of these data, the association of ciliary ultrastructural defect or genotype and likelihood of a laterality abnormality was evaluated by logistic regression adjusted for presence of two loss-of-function versus one or more not-loss-of-function variants. Results: Of 559 participants, 286 (51.2%), 215 (38.5%), and 58 (10.4%) were identified as having situs solitus, situs inversustotalis, and situs ambiguus, respectively; heterotaxy, defined as situs ambiguus with complex cardiovascular defects, was present in 14 (2.5%). Compared with the group with inner dynein arm defects with microtubular disorganization, laterality defects were more likely in the outer dynein arm defects group (odds ratio [OR], 2.07; 95% confidence interval [CI], 1.21-3.54; P < 0.01) and less likely in the normal/near normal ultrastructure group (OR, 0.04; 95% CI, 0.013-0.151; P < 0.01). Heterotaxy was present in 11 of 242 (4.5%) in the outer dynein arm defects group but 0 of 96 in the inner dynein arm defects with microtubular disorganization group (P = 0.038). Conclusion: In primary ciliary dyskinesia, risk of a laterality abnormality differs by ciliary ultrastructural defect. Pathophysiologic mechanisms underlying these differences require further exploration.

Airway Disease in Children with Primary Ciliary Dyskinesia: Impact of Ciliary Ultrastructure Defect and Genotype.

Rationale: Primary ciliary dyskinesia (PCD) is characterized by impaired mucociliary clearance, recurrent respiratory infections, progressive airway damage, and obstructive lung disease. Although the association of ciliary ultrastructure defect/genotype with the severity of airflow obstruction has been well characterized, their association with airway abnormalities on chest computed tomography (CT) has been minimally evaluated. Objectives: We sought to delineate the association of ciliary defect class/genotype with chest CT scores in children with PCD. Methods: Cross-sectional analysis of children with PCD (N = 146) enrolled in a prospective multicenter observational study, stratified by defect type: outer dynein arm (ODA), ODA/inner dynein arm (IDA), IDA/microtubular disorganization (MTD), and normal/near normal ultrastructure with associated genotypes. CTs were scored using the MERAGMA-PCD (Melbourne-Rotterdam Annotated Grid Morphometric Analysis for PCD), evaluating airway abnormalities in a hierarchical order: atelectasis, bronchiectasis, bronchial wall thickening, and mucus plugging/tree-in-bud opacities. The volume fraction of each component was expressed as the percentage of total lung volume. The percentage of disease was computed as the sum of all components. Regression analyses were used to describe the association between clinical predictors and CT scores. Results: Acceptable chest CTs were obtained in 141 children (71 male): 57 ODA, 20 ODA/IDA, 40 IDA/MTD, and 24 normal/near normal. The mean (standard deviation) age was 8.5 (4.6) years, forced expiratory volume in 1 second (FEV1) percent predicted was 82.4 (19.5), and %Disease was 4.6 (3.5). Children with IDA/MTD defects had a higher %Disease compared with children with ODA defects (2.71% higher [95% confidence interval (CI), 1.37-4.06; P < 0.001]), driven by higher %Mucus plugging (2.35% higher [1.43-3.26; P < 0.001]). Increasing age, lower body mass index, and lower FEV1 were associated with a higher %Disease (0.23%; 95% CI, 0.11-0.35; P < 0.001 and 0.03%; 95% CI, 0.01-0.04; P = 0.008 and 0.05%; 95% CI, 0.01-0.08; P = 0.011, respectively). Conclusions: Children with IDA/MTD defects had significantly greater airway disease on CT, primarily mucus plugging, compared with children with ODA defects.

The identification of gene expression profiles associated with progression of human diabetic neuropathy.

Diabetic neuropathy is a common complication of diabetes. While multiple pathways are implicated in the pathophysiology of diabetic neuropathy, there are no specific treatments and no means to predict diabetic neuropathy onset or progression. Here, we identify gene expression signatures related to diabetic neuropathy and develop computational classification models of diabetic neuropathy progression. Microarray experiments were performed on 50 samples of human sural nerves collected during a 52-week clinical trial. A series of bioinformatics analyses identified differentially expressed genes and their networks and biological pathways potentially responsible for the progression of diabetic neuropathy. We identified 532 differentially expressed genes between patient samples with progressing or non-progressing diabetic neuropathy, and found these were functionally enriched in pathways involving inflammatory responses and lipid metabolism. A literature-derived co-citation network of the differentially expressed genes revealed gene subnetworks centred on apolipoprotein E, jun, leptin, serpin peptidase inhibitor E type 1 and peroxisome proliferator-activated receptor gamma. The differentially expressed genes were used to classify a test set of patients with regard to diabetic neuropathy progression. Ridge regression models containing 14 differentially expressed genes correctly classified the progression status of 92% of patients (P < 0.001). To our knowledge, this is the first study to identify transcriptional changes associated with diabetic neuropathy progression in human sural nerve biopsies and describe their potential utility in classifying diabetic neuropathy. Our results identifying the unique gene signature of patients with progressive diabetic neuropathy will facilitate the development of new mechanism-based diagnostics and therapies.

Longitudinal declines in event-based, but not time-based, prospective memory among community-dwelling older adults.

Age-related deficits in prospective memory (PM) are well established, but it is not known whether PM is stable over time among older adults. In this study, 271 community-dwelling older adults underwent abaseline neuropsychological evaluation and up to three follow-up visits, approximately 2.4 years apart. Mixed effects linear longitudinal models revealed small, but significant linear declines and between-subjects variability in event-based PM performance. There were no changes in performance on measures of time-based PM, retrospective memory, or executive functions. Changes in event-based PM were not associated with age, retrospective memory, executive functions, or everyday functioning. Among older adults, event-based PM appears to be more susceptible to linear declines than does time-based PM, which future research might examine with regard to the possible underlying cognitive mechanisms of cue encoding, monitoring, detection, and retrieval processes.

Factor Structure of the Memory for Intentions Test (MIsT): A Conceptual Replication in Older Adults and People with HIV Disease.

OBJECTIVE: The Memory for Intentions Test (MIsT) is a clinical measure of prospective memory that has strong evidence for convergent, discriminative, and ecological validity. This study uses a conceptual replication design to evaluate the latent structure of the MIsT in two parallel samples who commonly experience prospective memory deficits: older adults and people living with HIV disease. PARTICIPANTS AND METHODS: Study participants included 303 people with HIV disease (ages 18-67) and 267 community-dwelling older adults (ages 50-91). Confirmatory factor analyses of the MIsT were conducted separately in each sample. We evaluated a one-factor model, as well as three two-factor models with the MIsT items loading onto each factor based on cue type, delay interval, or response modality. RESULTS: The one-factor model provided the best (and most parsimonious) fit to the data in both study samples. All two-factor models also demonstrated good fit statistics, although correlations between the two factors in each model were high and none of the two-factor models provided a significantly better fit than the one-factor model. CONCLUSIONS: Results of this conceptual replication study provide support for a robust factor structure of the MIsT across older adults and people with HIV disease. A total score for the MIsT provides the most parsimonious solution, although available evidence and theory also support the potential use of subscales (e.g., cue type). Future studies of the MIsT would be useful to determine its psychometrics in different clinical populations and across demographic factors (e.g., race/ethnicity).

The complementary utility of cognitive testing and the medication management ability assessment in older adults.

OBJECTIVE: Older adults are susceptible to cognitive declines that may limit independence. Though neuropsychologists opine about risk of functional decline, the degree to which cognitive testing and in-office simulations approximate everyday behavior is unclear. We assessed the complementary utility of cognitive testing and the face-valid Medication Management Ability Assessment (MMAA) to predict medication management among older adults. METHOD: This was a retrospective study of 234 older adults (age = 72 ± 7.7 years; 59% women) who completed the MMAA during outpatient neuropsychological evaluations. Based on comprehensive clinical assessment, most participants (n = 186) were independent in medication management, while 48 received assistance. Demographically adjusted composite scores were derived for attention/processing speed (A/PS), executive functioning (EF), visuospatial/constructional ability (VC), language, and memory domains. Univariate differences in cognition were examined across Assisted versus Independent groups. Logistic regression assessed which cognitive domains independently predicted group status. The incremental value of the MMAA was assessed, holding uniquely associated cognitive test scores constant. RESULTS: Those receiving assistance with medication management performed worse across all neurocognitive domains and the MMAA compared with independent counterparts. EF was the only unique cognitive predictor of medication management status. When modeled alone, EF and MMAA performance correctly classified 79.5% and 80.8% of cases, respectively. When modeled together, both were independently associated with medication management status and correctly classified 83.3% of cases. CONCLUSIONS: EF uniquely predicted medication management status beyond other cognitive domains. The MMAA provided complementary predictive utility. Concurrent interpretation of executive functioning and MMAA performance is advised when assessing older adults suspected of medication mismanagement. (PsycInfo Database Record (c) 2022 APA, all rights reserved).