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1.
Mil Med ; 2024 May 13.
Article in English | MEDLINE | ID: mdl-38739491

ABSTRACT

INTRODUCTION: The U.S. Military Veterans aged 65 and older comprise an estimated 43% of the 22 million living Veterans in the United States. Veterans have high rates of physical, psychiatric, and social challenges, but it is not known whether Veteran status confers additional risk for cognitive or functional impairments in later life. Thus, this investigation specifically compared older Veterans with their non-Veteran peers in cognitive functioning and performance-based functional capacity. MATERIALS AND METHODS: Participants (N = 110; 29 Veterans and 81 non-Veterans) were part of a larger longitudinal study on biopsychosocial functioning in independently living older adult residents of a Continuing Care Senior Housing Community. The University of California San Diego Institutional Review Board approved the study and all participants provided written informed consent. Participants provided demographic and mental health information and were administered a comprehensive neuropsychological battery. Functional capacity was assessed using the UCSD Performance-Based Skills Assessment-Brief (UPSA-B), which uses financial and communication role-plays to assess everyday functioning skills. Neuropsychological scores were appropriately normed prior to analysis. Multivariate Analyses of Variances with post hoc t-tests and an Analysis of Covariance were used to examine neuropsychological and functional capacity differences, respectively, between Veterans and non-Veterans. RESULTS: Veterans did not differ from non-Veterans in educational attainment (16.4 years versus 15.5 years, P = 0.110), but they were significantly older (mean age 86.9 years ± 5.7, versus 81.74 years ± 6.53; P < 0.001) and were more likely to be male (X2 [1, N = 110] = 62.39, P < 0.001). Thus, though neuropsychological norms already accounted for demographic differences in our participants, age and sex were controlled in the Analysis of Covariance predicting UPSA-B score from Veteran status. Results suggested that, compared to non-Veterans, Veterans had significantly worse performance in the list learning portion of a test of verbal memory (Hopkins Verbal Learning Test-Revised, Total Recall; t = 2.56, P = 0.012, d = 0.56). Veterans and non-Veterans did not significantly differ in performance on the delayed recall portion of the verbal learning test and did not differ on a cognitive screening test (Montreal Cognitive Assessment) or on measures of premorbid intellectual functioning (Wide Range Achievement Test-4 Reading), language (Boston Naming Test, Verbal Fluency), visual memory (Brief Visuospatial Memory Test-Revised), attention/working memory (WAIS-IV Digit Span), processing speed (WAIS-IV Digit Symbol Coding), executive function (Delis-Kaplan Executive Function System Trails and Color-Word Test), or functional capacity (UPSA-B). Because our examination of multiple outcomes might have inflated Type I error, we performed a post hoc adjustment of P values using Benjamini-Hochberg procedures and the group difference in verbal learning remained significant. CONCLUSIONS: Despite largely similar function in most domains, Veterans performed significantly more poorly in verbal list learning than their non-Veteran peers. Additional attention should be given to the understanding, assessment, and possible treatment of learning and memory differences in older Veterans, as this may be an area in which Veteran status confers additional risk or vulnerability to decline. This is the first study to compare objective neuropsychological and functional performance between older (age 65+) US Veterans and non-Veterans.

2.
Curr Pharm Teach Learn ; 16(2): 87-92, 2024 02.
Article in English | MEDLINE | ID: mdl-38158333

ABSTRACT

INTRODUCTION: Misconceptions related to terminology used in the diagnosis and treatment of substance use disorders are common among healthcare providers and may contribute to inappropriate management and education of patients. The objective of this study was to evaluate baseline knowledge of addiction, tolerance, and physical dependence in first-year pharmacy students completing a unit on the neurobiological basis of addiction. METHODS: Students were asked to define the terms addiction, tolerance, and dependence at the beginning of a didactic unit on nervous system pathophysiology and pharmacology. Handwritten responses were transcribed to a spreadsheet and deidentified by sequential assignment to a single numeric identifier. Data were analyzed by three reviewers through open coding and thematic analysis. Descriptive statistics were used to describe the results. RESULTS: One hundred eighty-seven individual student submitted responses were included in the analysis. Many students were unable to provide a substantive definition for the terms physical dependence (32%) and addiction (27%). The definition of tolerance was partially correct in >80% of student responses, though no students provided a complete description. Approximately 5% of students defined physical dependence as addiction, and > 18% incorrectly attributed withdrawal symptoms to addiction. CONCLUSIONS: Significant knowledge gaps or misconceptions regarding terminology related to substance use disorder exists among first-year pharmacy students despite continuing efforts within professional organizations to develop consensus definitions. Developing effective teaching methods to identify and correct misinformation and preconceptions related to care for patients with substance use disorders should continue to be a priority for pharmacy educators.


Subject(s)
Behavior, Addictive , Students, Pharmacy , Substance-Related Disorders , Humans , Substance-Related Disorders/drug therapy , Health Personnel
3.
Mil Med ; 2023 Nov 10.
Article in English | MEDLINE | ID: mdl-37966488

ABSTRACT

INTRODUCTION: Mild traumatic brain injury (mTBI), depression, and PTSD are highly prevalent in post-9/11 veterans. With the comorbidity of depression and PTSD in post-9/11 veterans with mTBI histories and their role in exacerbating cognitive and emotional dysfunction, interventions addressing cognitive and psychiatric functioning are critical. Compensatory Cognitive Training (CCT) is associated with improvements in prospective memory, attention, and executive functioning and has also yielded small-to-medium treatment effects on PTSD and depressive symptom severity. We sought to examine neuropsychological correlates of PTSD and depressive symptom improvement in veterans with a history of mTBI who received CCT. MATERIALS AND METHODS: Thirty-seven post-9/11 veterans with mTBI histories and cognitive complaints received 10 weekly 120-minute CCT group sessions. Participants completed a baseline neuropsychological assessment, including tests of premorbid functioning, attention/working memory, processing speed, verbal learning/memory, and executive functioning, and completed psychiatric symptom measures (PTSD and depression) at baseline, post-treatment, and a 5-week follow-up. Paired samples t-tests were used to examine statistically significant changes in PTSD (total and symptom cluster scores) and depressive symptom scores over time. Pearson's correlations were calculated between neuropsychological scores and PTSD and depressive symptom change scores at post-treatment and follow-up. Neuropsychological measures identified as significantly correlated with psychiatric symptom change scores were entered as independent variables in multivariable regression analyses to examine their association with symptom change at post-treatment and follow-up. RESULTS: Over 50% of CCT participants had clinically meaningful improvement in depressive symptoms (≥17.5% score reduction), and over 20% had clinically meaningful improvement in PTSD symptoms (≥10-point improvement) at post-treatment and follow-up. Examination of PTSD symptom cluster scores revealed a statistically significant improvement in avoidance/numbing at follow-up. Bivariate correlations indicated that worse baseline performance on Category Fluency was moderately associated with PTSD symptom improvement at post-treatment. Worse performance on both Category Fluency and Category Switching Accuracy was associated with improvement in depressive symptoms at post-treatment and follow-up. Worse performance on Trail-Making Number-Letter Switching was also associated with improvement in depressive symptoms at follow-up. Subsequent regression analyses revealed that worse processing speed and worse aspects of executive functioning at baseline were associated with depressive symptom improvement at post-treatment and follow-up. CONCLUSIONS: Worse baseline performances on tests of processing speed and aspects of executive functioning were significantly associated with improvements in PTSD and depressive symptoms during the trial. Our results suggest that cognitive training may bolster skills that are helpful for PTSD and depressive symptom reduction and that those with worse baseline functioning may benefit more from treatment because they have more room to improve.

4.
Circulation ; 148(16): 149-184, 20231017. tab
Article in English | BIGG - GRADE guidelines | ID: biblio-1525929

ABSTRACT

In this focused update, the American Heart Association provides updated guidance for resuscitation of patients with cardiac arrest, respiratory arrest, and refractory shock due to poisoning. Based on structured evidence reviews, guidelines are provided for the treatment of critical poisoning from benzodiazepines, ß-adrenergic receptor antagonists (also known as ß-blockers), L-type calcium channel antagonists (commonly called calcium channel blockers), cocaine, cyanide, digoxin and related cardiac glycosides, local anesthetics, methemoglobinemia, opioids, organophosphates and carbamates, sodium channel antagonists (also called sodium channel blockers), and sympathomimetics. Recommendations are also provided for the use of venoarterial extracorporeal membrane oxygenation. These guidelines discuss the role of atropine, benzodiazepines, calcium, digoxin-specific immune antibody fragments, electrical pacing, flumazenil, glucagon, hemodialysis, hydroxocobalamin, hyperbaric oxygen, insulin, intravenous lipid emulsion, lidocaine, methylene blue, naloxone, pralidoxime, sodium bicarbonate, sodium nitrite, sodium thiosulfate, vasodilators, and vasopressors for the management of specific critical poisonings.


Subject(s)
Humans , Cardiopulmonary Resuscitation , Advanced Cardiac Life Support/standards , Drug Overdose/complications , Poisoning/complications , Heart Arrest/therapy , Antidotes/therapeutic use
5.
Circulation ; 148(16): e149-e184, 2023 10 17.
Article in English | MEDLINE | ID: mdl-37721023

ABSTRACT

In this focused update, the American Heart Association provides updated guidance for resuscitation of patients with cardiac arrest, respiratory arrest, and refractory shock due to poisoning. Based on structured evidence reviews, guidelines are provided for the treatment of critical poisoning from benzodiazepines, ß-adrenergic receptor antagonists (also known as ß-blockers), L-type calcium channel antagonists (commonly called calcium channel blockers), cocaine, cyanide, digoxin and related cardiac glycosides, local anesthetics, methemoglobinemia, opioids, organophosphates and carbamates, sodium channel antagonists (also called sodium channel blockers), and sympathomimetics. Recommendations are also provided for the use of venoarterial extracorporeal membrane oxygenation. These guidelines discuss the role of atropine, benzodiazepines, calcium, digoxin-specific immune antibody fragments, electrical pacing, flumazenil, glucagon, hemodialysis, hydroxocobalamin, hyperbaric oxygen, insulin, intravenous lipid emulsion, lidocaine, methylene blue, naloxone, pralidoxime, sodium bicarbonate, sodium nitrite, sodium thiosulfate, vasodilators, and vasopressors for the management of specific critical poisonings.


Subject(s)
Cardiopulmonary Resuscitation , Heart Arrest , Humans , Adrenergic beta-Antagonists , American Heart Association , Benzodiazepines , Digoxin , Heart Arrest/chemically induced , Heart Arrest/therapy , United States
6.
Nutrients ; 15(9)2023 Apr 30.
Article in English | MEDLINE | ID: mdl-37432267

ABSTRACT

Exposure to adverse early-life environments (AME) increases the incidence of developing adult-onset non-alcoholic fatty liver disease (NAFLD). DNA methylation has been postulated to link AME and late-onset diseases. This study aimed to investigate whether and to what extent the hepatic DNA methylome was perturbed prior to the development of NAFLD in offspring exposed to AME in mice. AME constituted maternal Western diet and late-gestational stress. Male offspring livers at birth (d0) and weaning (d21) were used for evaluating the DNA methylome and transcriptome using the reduced representation of bisulfite sequencing and RNA-seq, respectively. We found AME caused 5879 differentially methylated regions (DMRs) and zero differentially expressed genes (DEGs) at d0 and 2970 and 123, respectively, at d21. The majority of the DMRs were distal to gene transcription start sites and did not correlate with DEGs. The DEGs at d21 were significantly enriched in GO biological processes characteristic of liver metabolic functions. In conclusion, AME drove changes in the hepatic DNA methylome, which preceded perturbations in the hepatic metabolic transcriptome, which preceded the onset of NAFLD. We speculate that subtle impacts on dynamic enhancers lead to long-range regulatory changes that manifest over time as gene network alternations and increase the incidence of NAFLD later in life.


Subject(s)
Non-alcoholic Fatty Liver Disease , Male , Animals , Mice , Pregnancy , Female , Non-alcoholic Fatty Liver Disease/genetics , Epigenome , Transcriptome , DNA Methylation
7.
Resusc Plus ; 14: 100375, 2023 Jun.
Article in English | MEDLINE | ID: mdl-37007185

ABSTRACT

Immediate bystander CPR after an out-of-hospital-cardiac arrest is likely to save hundreds of thousands of lives worldwide each year. International Liaison Committee on Resuscitation launched the World Restart a Heart initiative on October 16, 2018. In 2021 more than 2,200,000 persons were trained and at least 302,000,000 people were reached by WRAH global collaboration through print and digital media making it the highest-impact year since its inception. We strive for real success when CPR training and awareness become a year-round activity in all countries and all the citizens of the world realize that "Two Hands Can Save a Life!"

8.
Clin Neuropsychol ; 37(8): 1728-1744, 2023 Nov.
Article in English | MEDLINE | ID: mdl-36772819

ABSTRACT

Objective: Returning Veterans often have conditions (e.g. posttraumatic stress disorder [PTSD], depression, and history of traumatic brain injury [TBI]) associated with cognitive dysfunction and problems with work, school, housing, and relationships. Rehabilitative efforts in Veterans aim to promote community reintegration, or successful adjustment in one's home, community, and desired social roles. We examined associations between neuropsychological performance, neurobehavioral symptoms, and community reintegration in Veterans. Method: 89 Iraq/Afghanistan Veterans at risk for homelessness and receiving residential mental healthcare completed a neuropsychological assessment and the Community Reintegration for Service Members-Computer Adaptive Test (CRIS-CAT). Neuropsychological components were derived using Principal Component Analysis. Bivariate Pearson correlations between neuropsychological variables, neurobehavioral symptoms, and CRIS-CAT scales (Extent of Participation, Perceived Limitations, and Satisfaction) were used to determine significant correlates of community reintegration. Regression models were used to examine associations between bivariate-significant neuropsychological components, neurobehavioral symptoms, and CRIS-CAT scales. Results: Bivariate analyses revealed that better community reintegration was associated with better performance in attention/executive functioning and fewer neurobehavioral symptoms. Three regression models examining predictors of variance in Extent of Participation, Perceived Limitations, and Satisfaction in community reintegration were statistically significant overall, with only fewer affective symptoms emerging as significantly and uniquely associated with greater participation and greater satisfaction in community functioning. Conclusions: Veterans with fewer affective symptoms reported greater participation and satisfaction with community functioning. Future longitudinal research examining associations between neurobehavioral symptoms, cognition, and risk factors of poorer community reintegration in unstably housed Veterans is warranted.

9.
Int J Aging Hum Dev ; 96(1): 3-5, 2023 01.
Article in English | MEDLINE | ID: mdl-35815703

ABSTRACT

The following papers represent an early contribution of the National Institute on Aging's commitment to support high-quality research and mentor a more diverse workforce in the field of aging. The International Journal of Aging and Human Development has previously issued calls for such scholarship and has provided opportunities to share some of their teaching techniques that foster and support the next generation of gerontologists. In this issue, we feature both lessons learned from those who design and supervise National Institute of Aging-supported training programs and we highlight some of the work that these diverse scholars are contributing to the field. We hope that by disseminating "lessons learned" and specific research pieces, other labs will begin similar programs. We encourage others to develop and implement innovative training models and explore some of the funding opportunities available to support increasing diversity in aging.


Subject(s)
Aging , Geroscience , Humans , Workforce
10.
J Psychiatr Res ; 151: 347-353, 2022 07.
Article in English | MEDLINE | ID: mdl-35533518

ABSTRACT

Individuals with schizophrenia who have high negative symptoms are at high risk for poor functional outcomes. However, the determinants of psychosocial functioning in this group are not well understood. We aimed to examine modifiable predictors of both objective, performance-based functional capacity and social skills, and self-reported functioning in individuals with schizophrenia and schizoaffective disorder and high negative symptoms. Fifty-five adults with moderate-to-severe negative symptoms were administered measures of neuropsychological performance, performance-based functional capacity and social competence, self-reported functioning, psychiatric symptom severity, defeatist/asocial beliefs, and intrinsic motivation. In the context of multiple significant predictor variables identified through bivariate correlations, multiple regression models showed that neuropsychological performance was the only significant predictor of performance-based functional capacity; neuropsychological performance and motivation/pleasure negative symptoms were significant predictors of performance-based social competence. For two different measures of self-reported functioning, intrinsic motivation, asocial beliefs, and diminished expression emerged as significant predictors. Neurocognitive ability was a better predictor of performance-based functional skills whereas motivation and beliefs more strongly predicted self-reported real-world functioning. The findings of this study suggest a complex picture of predictors of performance-based functional capacity (objective neuropsychological functioning) and self-reported functioning (motivation and beliefs), underscoring the clinical and scientific utility of including both self-reported and objective measures of functioning to identify treatment approach. Individuals with high negative symptoms and a cognitive/functional skills deficit may benefit from interventions such as cognitive remediation or skills training, whereas individuals with motivational difficulties may benefit from treatments such as cognitive behavioral therapy.


Subject(s)
Psychotic Disorders , Schizophrenia , Adult , Humans , Neuropsychological Tests , Psychotic Disorders/psychology , Schizophrenic Psychology , Self Report
11.
Sci Transl Med ; 14(632): eabm4107, 2022 02 16.
Article in English | MEDLINE | ID: mdl-35171651

ABSTRACT

Alzheimer's disease (AD) is the most dominant form of dementia characterized by the deposition of extracellular amyloid plaques and intracellular neurofibrillary tau tangles (NFTs). In addition to these pathologies, an emerging pathophysiological mechanism that influences AD is neuroinflammation. Astrocytes are a vital type of glial cell that contribute to neuroinflammation, and reactive astrocytes, or astrogliosis, are a well-known pathological feature of AD. However, the mechanisms by which astrocytes contribute to the neurodegenerative process in AD have not been fully elucidated. Here, we showed that astrocytic α2-Na+/K+ adenosine triphosphatase (α2-NKA) is elevated in postmortem human brain tissue from AD and progressive nuclear palsy, a primary tauopathy. The increased astrocytic α2-NKA was also recapitulated in a mouse model of tauopathy. Pharmacological inhibition of α2-NKA robustly suppressed neuroinflammation and reduced brain atrophy. In addition, α2-NKA knockdown in tauopathy mice halted the accumulation of tau pathology. We also demonstrated that α2-NKA promoted tauopathy, in part, by regulating the proinflammatory protein lipocalin-2 (Lcn2). Overexpression of Lcn2 in tauopathy mice increased tau pathology, and prolonged Lcn2 exposure to primary neurons promoted tau uptake in vitro. These studies collectively highlight the contribution of reactive astrocytes to tau pathogenesis in mice and define α2-NKA as a major regulator of astrocytic-dependent neuroinflammation.


Subject(s)
Alzheimer Disease , Tauopathies , Adenosine Triphosphatases/metabolism , Alzheimer Disease/pathology , Animals , Astrocytes/metabolism , Disease Models, Animal , Mice , Mice, Transgenic , Neurofibrillary Tangles/metabolism , Tauopathies/metabolism , tau Proteins/metabolism
12.
Schizophr Bull ; 48(2): 359-370, 2022 03 01.
Article in English | MEDLINE | ID: mdl-34665853

ABSTRACT

OBJECTIVE: Negative symptoms and cognitive impairment in schizophrenia (SZ) remain unmet treatment needs as they are highly prevalent, associated with poor functional outcomes, and resistant to pharmacologic treatment. The current pilot randomized controlled trial examined the efficacy of an integrated Cognitive-Behavioral Social Skills Training and Compensatory Cognitive Training (CBSST-CCT) intervention compared to Goal-focused Supportive Contact (SC) on negative symptoms and cognitive performance. METHODS: Fifty-five adults with SZ or schizoaffective disorder with moderate-to-severe negative symptoms were randomized to receive 25 twice-weekly, 1-h manualized group sessions (12.5 weeks total duration) of either CBSST-CCT or SC delivered by master's level clinicians in five community settings. Assessments of negative symptom severity (primary outcomes) and neuropsychological performance, functional capacity, social skills performance, and self-reported functional ability/everyday functioning, psychiatric symptom severity, and motivation (secondary outcomes) were administered at baseline, mid-treatment, post-treatment, and 6-month follow-up. RESULTS: Mixed-effects models using baseline, mid-treatment, and post-treatment data demonstrated significant CBSST-CCT-associated effects on negative symptom severity, as assessed by the Scale for the Assessment of Negative Symptoms (p = .049, r = 0.22), with improvements in diminished motivation driving this effect (p = .037, r = 0.24). The CBSST-CCT group also demonstrated improved verbal learning compared to SC participants (p = .026, r = 0.36). The effects of CBSST-CCT appeared to be durable at 6-month follow-up. CONCLUSIONS: CBSST-CCT improved negative symptom severity and verbal learning in high-negative-symptom individuals relative to SC. CBSST-CCT warrants larger investigations to examine its efficacy in treating negative symptoms, along with other symptoms, cognition, and, ultimately, real-world functional outcomes. Clinical Trial registration number NCT02170051.


Subject(s)
Cognitive Behavioral Therapy/methods , Neuropsychological Tests/statistics & numerical data , Psychotic Disorders/therapy , Adult , Cognitive Behavioral Therapy/statistics & numerical data , Female , Humans , Male , Middle Aged , Pilot Projects , Psychotic Disorders/psychology , Social Skills , Treatment Outcome
13.
Clin Neuropsychol ; 36(8): 2073-2092, 2022 11.
Article in English | MEDLINE | ID: mdl-34524071

ABSTRACT

OBJECTIVE: Executive dysfunction has previously been associated with suicidality, but it remains unclear how deficits in executive functioning contribute to increased suicidal thoughts and behaviors. Although it has been proposed that poorer executive functioning leads to difficulty generating and implementing appropriate coping strategies to regulate distress and inhibit suicidal thoughts and behaviors, studies have not systematically examined these relationships. Therefore, the present study examined various hypotheses to elucidate the mechanisms through which executive dysfunction influences suicidal ideation (SI) in combat-exposed Iraq/Afghanistan veterans. METHOD: Veterans who endorsed SI were compared to those who denied SI on demographic and diagnostic variables and measures of neuropsychological functioning, psychological symptoms, coping styles, and combat experiences. Serial mediation models were tested to examine mechanistic relationships among executive functioning, psychological distress, coping, and SI. RESULTS: Those who endorsed SI had worse executive functioning, greater psychological distress, and greater avoidant coping relative to those who denied SI. Serial mediation model testing indicated a significant indirect path, such that executive dysfunction increased psychological distress, which in turn increased avoidant coping, leading to SI. CONCLUSIONS: Findings support and extend previous hypotheses regarding how executive functioning contributes to increased risk of suicidality via increased distress and avoidant coping. Intervention efforts focused on reducing suicidality may benefit from techniques that enhance executive functioning (e.g. computerized training, cognitive rehabilitation) and in turn reduce distress prior to targeting coping strategies.


Subject(s)
Stress Disorders, Post-Traumatic , Veterans , Humans , Veterans/psychology , Suicidal Ideation , Iraq War, 2003-2011 , Afghan Campaign 2001- , Afghanistan , Iraq , Neuropsychological Tests , Stress Disorders, Post-Traumatic/psychology
14.
Am J Orthopsychiatry ; 92(1): 103-108, 2022.
Article in English | MEDLINE | ID: mdl-34914414

ABSTRACT

Suicide prevention among Veterans is a national priority. Overlap exists between conditions that may increase risk for suicide (e.g., mental health conditions, financial stressors, lack of social support) and homelessness among Veterans. We examined predictors of variance in suicidal ideation (SI) among 58 Iraq/Afghanistan Veterans at risk for homelessness who were receiving residential mental health treatment. Participants were classified as SI nonendorsers (n = 36) or SI endorsers (n = 22), based on their Patient Health Questionnaire-9 (PHQ-9) responses. Independent t tests and chi-square tests were used to examine group differences on baseline demographic variables, neuropsychological measures, and emotional/physical health symptom measures. Compared to nonendorsers, SI endorsers were significantly younger and reported less Veterans Affairs (VA) disability income, less total monthly income, less physical pain, lower quality of life overall and in the psychological health domain, lower community reintegration satisfaction, and more severe anxiety. Groups did not significantly differ on cognitive measures. A subsequent logistic regression revealed that only younger age uniquely predicted variance in SI endorsement. Younger age may be a particularly important factor to consider when assessing suicide risk in Veterans at risk for homelessness. Identifying predictors of variance in SI may help inform future treatment and suicide prevention efforts for Veterans at risk for homelessness. Future longitudinal research examining predictors of suicidality is warranted. (PsycInfo Database Record (c) 2022 APA, all rights reserved).


Subject(s)
Ill-Housed Persons , Stress Disorders, Post-Traumatic , Veterans , Afghan Campaign 2001- , Afghanistan , Humans , Iraq , Iraq War, 2003-2011 , Mental Health , Quality of Life , Risk Factors , Suicidal Ideation
15.
J Nutr ; 151(10): 3102-3112, 2021 10 01.
Article in English | MEDLINE | ID: mdl-34486661

ABSTRACT

BACKGROUND: The role of an adverse maternal environment (AME) in conjunction with a postweaning Western diet (WD) in the development of nonalcoholic fatty liver disease (NAFLD) in adult offspring has not been explored. Likewise, the molecular mechanisms associated with AME-induced NAFLD have not been studied. The fatty acid translocase or cluster of differentiation 36 (CD36) has been implicated to play a causal role in the pathogenesis of WD-induced steatosis. However, it is unknown if CD36 plays a role in AME-induced NAFLD. OBJECTIVE: This study was designed to evaluate the isolated and additive impact of AME and postweaning WD on the expression and DNA methylation of hepatic Cd36 in association with the development of NAFLD in a novel mouse model. METHODS: AME constituted maternal WD and maternal stress, whereas the control (Con) group had neither. Female C57BL/6J mice were fed a WD [40% fat energy, 29.1% sucrose energy, and 0.15% cholesterol (wt/wt)] 5 wk prior to pregnancy and throughout lactation. Non invasive variable stressors (random frequent cage changing, limited bedding, novel object, etc.) were applied to WD dams during the last third of pregnancy to produce an AME. Con dams consumed the control diet (CD) (10% fat energy, no sucrose or cholesterol) and were not exposed to stress. Male offspring were weaned onto either CD or WD, creating 4 experimental groups: Con-CD, Con-WD, AME-CD, and AME-WD, and evaluated for metabolic and molecular parameters at 120 d of age. RESULTS: AME and postweaning WD independently and additively increased the development of hepatic steatosis in adult male offspring. AME and WD independently and additively upregulated hepatic CD36 protein and mRNA expression and hypomethylated promoters 2 and 3 of the Cd36 gene. CONCLUSIONS: Using a mouse AME model together with postweaning WD, this study demonstrates a role for CD36 in AME-induced NAFLD in offspring and reveals 2 regions of environmentally induced epigenetic heterogeneity within Cd36.


Subject(s)
Non-alcoholic Fatty Liver Disease , Animals , DNA Methylation , Diet, High-Fat/adverse effects , Diet, Western/adverse effects , Female , Liver/metabolism , Male , Mice , Mice, Inbred C57BL , Non-alcoholic Fatty Liver Disease/etiology , Non-alcoholic Fatty Liver Disease/metabolism , Pregnancy
16.
JPEN J Parenter Enteral Nutr ; 45(8): 1653-1662, 2021 11.
Article in English | MEDLINE | ID: mdl-34350991

ABSTRACT

BACKGROUND: Overprescribing of parenteral nutrition (PN) increases costs and risks to patients, including from central line-associated bloodstream infection (CLABSI). With CLABSI reduction in mind, our children's hospital began an iterative quality improvement effort to decrease PN utilization by first ensuring appropriate initiation and then defining and ensuring appropriate discontinuation. METHODS: Education was launched along with audits to evaluate for appropriate PN indications. Next, a literature review was conducted to guide the development of an algorithm to appropriately wean and discontinue PN. Lastly, all PN discontinuations were audited for agreement with the new guideline. Retrospectively, monthly PN utilization index (orders per patient-day) was plotted on a statistical process control chart to assess change over time. The presence of PN as a risk factor for CLABSI events and the overall hospital CLABSI rate were trended. RESULTS: Mean PN utilization index fell from 0.156 (July 2018 to January 2019) to 0.12 (February 2019 to August 2020) (P < .01). For 18 months, no PN utilization index reached the baseline lower control limit of 0.144, demonstrating special-cause variation and sustained change. PN as a risk factor for hospital CLABSI cases decreased from most prevalent (49% of cases) to fifth most prevalent (29%) as the CLABSI rate trended down. CONCLUSION: Engaging frontline staff in the development of a clinical practice guideline and increased accountability to reduce potential patient harm led to a significant and sustained reduction in PN utilization, as well as decreased prevalence of PN as a risk factor in hospital CLABSI cases.


Subject(s)
Catheter-Related Infections , Catheterization, Central Venous , Sepsis , Catheter-Related Infections/epidemiology , Catheter-Related Infections/etiology , Catheter-Related Infections/prevention & control , Catheterization, Central Venous/adverse effects , Child , Child, Hospitalized , Humans , Parenteral Nutrition/adverse effects , Quality Improvement , Retrospective Studies , Sepsis/etiology , Weaning
17.
J Neuropsychiatry Clin Neurosci ; 33(2): 98-108, 2021.
Article in English | MEDLINE | ID: mdl-33441014

ABSTRACT

OBJECTIVE: The investigators sought to evaluate the independent and interactive associations between mild traumatic brain injury (mTBI) characteristics and posttraumatic stress disorder (PTSD) symptoms with regard to postconcussive symptoms and cognition among treatment-seeking veterans of the U.S. conflicts in Iraq and Afghanistan. METHODS: Sixty-seven Iraq and Afghanistan veterans who had a history of mTBI and comorbid PTSD were grouped based on injury mechanism (blast versus nonblast) and number of lifetime mTBIs (one to two versus three or more). Independent associations between mTBI characteristics and PTSD symptom clusters were evaluated with regard to cognition and postconcussive symptoms. Follow-up analyses were conducted to determine any interactive associations between TBI characteristics and PTSD symptom clusters. RESULTS: Higher PTSD symptoms, particularly hyperarousal, were associated with poorer executive functioning and higher postconcussive symptoms. No direct relationships were observed between PTSD symptom clusters and memory or processing speed. The relationship between hyperarousal and processing speed was moderated by lifetime mTBIs, such that those with a history of at least three mTBIs demonstrated a negative association between hyperarousal and processing speed. Blast-related mTBI history was associated with reduced processing speed, compared with non-blast-related mTBI. However, an interaction was observed such that among those with blast-related mTBI history, higher re-experiencing symptoms were associated with poorer processing speed, whereas veterans without history of blast-related mTBI did not demonstrate an association between processing speed and re-experiencing symptoms. CONCLUSIONS: Higher hyperarousal and re-experiencing symptoms were associated with reduced processing speed among veterans with repetitive and blast-related mTBI history, respectively. PTSD symptoms, specifically hyperarousal, were associated with poorer executive functioning and higher postconcussive symptoms. Limited associations were found between injury characteristics and cognition chronically following mTBI. However, these results support synergistic effects of specific PTSD symptom clusters and TBI characteristics.


Subject(s)
Afghan Campaign 2001- , Blast Injuries/complications , Brain Concussion/epidemiology , Cognition , Iraq War, 2003-2011 , Neuropsychological Tests/statistics & numerical data , Post-Concussion Syndrome , Stress Disorders, Post-Traumatic/epidemiology , Veterans/statistics & numerical data , Adult , Executive Function , Humans , Male
18.
Psychiatr Serv ; 72(3): 333-337, 2021 03 01.
Article in English | MEDLINE | ID: mdl-33397143

ABSTRACT

OBJECTIVE: This study examined rates of objective cognitive and functional impairments and associations between cognitive performance and performance-based functional capacity in a well-characterized sample of adults experiencing homelessness. METHODS: One hundred participants completed a brief neuropsychological and functional capacity assessment and self-report questionnaires. Cognitive impairment rates were determined by comparing mean scores with published normative data, as well as by examining frequency of scores >1 SD below the mean. Pearson correlations were used to examine associations between cognitive and functional capacities. RESULTS: Overall, 65% of the study participants had scores in the cognitively impaired range on a brief cognitive screening test, 30% had impaired processing speed, and 11% met cognitive criteria for intellectual disability. Furthermore, 48% of the sample met functional impairment criteria, and poorer cognitive performance was strongly associated with poorer performance-based functional capacity (p<0.001). CONCLUSIONS: Cognitive and functional impairments are common among sheltered adults experiencing homelessness, underscoring the need for routine objective cognitive screening and rehabilitation services.


Subject(s)
Cognition Disorders , Cognitive Dysfunction , Ill-Housed Persons , Adult , Cognition , Cognition Disorders/epidemiology , Cognitive Dysfunction/epidemiology , Humans , Neuropsychological Tests
20.
Psychiatry Res ; 295: 113620, 2021 01.
Article in English | MEDLINE | ID: mdl-33290939

ABSTRACT

The current study examined the feasibility and acceptability of an integrated Cognitive-Behavioral Social Skills Training and Compensatory Cognitive Training (CBSST-CCT) intervention compared with Goal-Focused Supportive Contact (SC) in a pilot randomized controlled trial for people with schizophrenia with high negative symptom severity. The sample included 55 participants from five community settings; masters-level study clinicians delivered interventions on-site. Participants completed assessments of cognitive, functional, and psychiatric symptoms at baseline, mid-treatment, post-treatment (12.5 weeks), and 6-month follow-up. Enrollment goals were not initially met, necessitating the addition of a fifth site; however, all groups and assessments were completed on-site. Study procedures were acceptable, as evidenced by 100% enrollment and completion of baseline assessments following informed consent; however, over 1/3rd of participants dropped out. No modifications were necessary to the intervention procedures and CBSST-CCT fidelity ratings were acceptable. The intervention was deemed acceptable among participants who attended ≥1 session, as evidenced by similar attendance rates in CBSST-CCT compared to SC. Among CBSST-CCT participants, lower positive symptoms were significantly associated with better attendance. Overall, we found mixed evidence for the feasibility and acceptability of the CBSST-CCT protocol in people with schizophrenia with high negative symptoms. Challenges are highlighted and recommendations for future investigations are provided.


Subject(s)
Cognitive Behavioral Therapy/methods , Patient Acceptance of Health Care/psychology , Schizophrenia/diagnosis , Schizophrenia/therapy , Schizophrenic Psychology , Social Skills , Adult , Aged , Cognition/physiology , Feasibility Studies , Female , Follow-Up Studies , Humans , Male , Middle Aged , Pilot Projects
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