Food, Food Stamps and Nutrition: An Evaluation of Methods of Recruitment and Instruction ; Public Communications Campaigns; Cartoons: When are they Effective; Science Meets the Press; Multimedia Instruction: High Learning, Low Cost

Reviews of Food, Food Stamps and Nutrition: An Evaluation of Methods of Recruitment and Instruction, by Richard A. Krueger and Bethaviva Cohen; Public Communication Campaigns, edited by Ronald E. Rice and William J. Paisley; Cartoons: When are they Effective, by James M. Nehiley, James Stephens, and John Sutherland; Science Meets the Press, by William E. Burrows; Multimedia Instruction: High Learning, Low Cost, by Karin Kristiansson

Hypercholesterolemia and microvascular dysfunction: interventional strategies

Hypercholesterolemia is defined as excessively high plasma cholesterol levels, and is a strong risk factor for many negative cardiovascular events. Total cholesterol levels above 200 mg/dl have repeatedly been correlated as an independent risk factor for development of peripheral vascular (PVD) and coronary artery disease (CAD), and considerable attention has been directed toward evaluating mechanisms by which hypercholesterolemia may impact vascular outcomes; these include both results of direct cholesterol lowering therapies and alternative interventions for improving vascular function. With specific relevance to the microcirculation, it has been clearly demonstrated that evolution of hypercholesterolemia is associated with endothelial cell dysfunction, a near-complete abrogation in vascular nitric oxide bioavailability, elevated oxidant stress, and the creation of a strongly pro-inflammatory condition; symptoms which can culminate in profound impairments/alterations to vascular reactivity. Effective interventional treatments can be challenging as certain genetic risk factors simply cannot be ignored. However, some hypercholesterolemia treatment options that have become widely used, including pharmaceutical therapies which can decrease circulating cholesterol by preventing either its formation in the liver or its absorption in the intestine, also have pleiotropic effects with can directly improve peripheral vascular outcomes. While physical activity is known to decrease PVD/CAD risk factors, including obesity, psychological stress, impaired glycemic control, and hypertension, this will also increase circulating levels of high density lipoprotein and improving both cardiac and vascular function. This review will provide an overview of the mechanistic consequences of the predominant pharmaceutical interventions and chronic exercise to treat hypercholesterolemia through their impacts on chronic sub-acute inflammation, oxidative stress, and microvascular structure/function relationships

Diabetes Mellitus Affects Working Memory

Alzheimer’s disease (AD) degrades the brain’s ability to remember, think, and carry out tasks. The exact cause is not known, but several risk factors have been identified, including diabetes mellitus (DM). DM causes elevated blood sugar levels due to reduced insulin production in the pancreas. The linkage between elevated glucose levels and the behavioral impairments are not fully understood, which was the focus of this study. Rats were trained to alternate directions in a maze to receive a reward on consecutive trials. After training, five rats were injected with streptozotocin (STZ), which induces hyperglycemia by injuring pancreatic beta cells. Three control animals received benign vehicle injections. All eight rats then underwent implant surgery and received an implant with 128 recording probes attached to an electronic interface board. The recording electrodes targeted the hippocampus and the anterior cingulate cortex (ACC), which are both associated with learning and memory processes. We found that STZ rats had reduced accuracy after long delay periods compared to the control rats. During task performance, there was a decrease in the power of theta activity and an increase in delta activity moments before starting a new trial. This was the opposite of control animals, who before starting new trials had higher theta power and less delta power as they focused. These findings imply that the STZ rats were impaired on longer delay periods. These findings are like reports from animal models of AD and may help explain why DM is a risk factor for AD

Rasagiline Effects on Glucose Metabolism, Cognition, and Tau in Alzheimer’s Dementia

Background: A Phase II proof of concept (POC) randomized clinical trial was conducted to evaluate the effects of rasagiline, a monoamine oxidase B (MAO-B) inhibitor approved for Parkinson disease, in mild to moderate Alzheimer\u27s disease (AD). The primary objective was to determine if 1 mg of rasagiline daily for 24 weeks is associated with improved regional brain metabolism (fluorodeoxyglucose–positron emission tomography [FDG-PET]) compared to placebo. Secondary objectives included measurement of effects on tau PET and evaluation of directional consistency of clinical end points. Methods: This was a double-blind, parallel group, placebo-controlled, community-based, three-site trial of 50 participants randomized 1:1 to receive oral rasagiline or placebo (NCT02359552). FDG-PET was analyzed for the presence of an AD-like pattern as an inclusion criterion and as a longitudinal outcome using prespecified regions of interest and voxel-based analyses. Tau PET was evaluated at baseline and longitudinally. Clinical outcomes were analyzed using an intention-to-treat (ITT) model. Results: Fifty patients were randomized and 43 completed treatment. The study met its primary end point, demonstrating favorable change in FDG-PET differences in rasagiline versus placebo in middle frontal (P \u3c 0.025), anterior cingulate (P \u3c 0.041), and striatal (P \u3c 0.023) regions. Clinical measures showed benefit in quality of life (P \u3c 0.04). Digit Span, verbal fluency, and Neuropsychiatric Inventory (NPI) showed non-significant directional favoring of rasagiline; no effects were observed in Alzheimer\u27s Disease Assessment Scale-Cognitive Subscale (ADAS-cog) or activities of daily living. Rasagiline was generally well tolerated with low rates of adverse events and notably fewer neuropsychiatric symptoms in the active treatment group. Discussion: These outcomes illustrate the potential benefits of rasagiline on clinical and neuroimaging measures in patients with mild to moderate AD. Rasagiline appears to affect neuronal activity in frontostriatal pathways, with associated clinical benefit potential warranting a more fully powered trial. This study illustrated the potential benefit of therapeutic repurposing and an experimental medicine proof-of-concept design with biomarkers to characterize patient and detect treatment response

Altered Theta Rhythm and Hippocampal-Cortical Interactions Underlie Working Memory Deficits in a Hyperglycemia Risk Factor Model of Alzheimer’s Disease

Diabetes mellitus is a metabolic disease associated with dysregulated glucose and insulin levels and an increased risk of developing Alzheimer’s disease (AD) later in life. It is thought that chronic hyperglycemia leads to neuroinflammation and tau hyperphosphorylation in the hippocampus leading to cognitive decline, but effects on hippocampal network activity are unknown. A sustained hyperglycemic state was induced in otherwise healthy animals and subjects were then tested on a spatial delayed alternation task while recording from the hippocampus and anterior cingulate cortex (ACC). Hyperglycemic animals performed worse on long delay trials and had multiple electrophysiological differences throughout the task. We found increased delta power and decreased theta power in the hippocampus, which led to altered theta/delta ratios at the end of the delay period. Cross frequency coupling was significantly higher in multiple bands and delay period hippocampus-ACC theta coherence was elevated, revealing hypersynchrony. The highest coherence values appeared long delays on error trials for STZ animals, the opposite of what was observed in controls, where lower delay period coherence was associated with errors. Consistent with previous investigations, we found increases in phosphorylated tau in STZ animals’ hippocampus and cortex, which might account for the observed oscillatory and cognitive changes. To investigate the effects of chronic hyperglycemia on hippocampal network activity Wirt et al induced sustained hyperglycemia in rats and tested them in a spatial delayed alternation task while recording from the hippocampus and anterior cingulate cortex. They demonstrated that hyperglycemia impaired task performance and altered theta rhythm as well as increasing tau phosphorylation, which suggest there is potentially a direct link between chronic hyperglycemia and Alzheimer’s disease

Paradox in the pursuit of a critical theorization of the development of self in family relationships

This article starts with my dissatisfaction with the post-structuralist treatment of the production of subjectivity within regulatory discourses and practices due to its neglect of psychological processes. Taking starting points from within the history set out in the previous article, it highlights the paradox for critical psychologists like myself involved in both applying a post-structuralist critique to 'psy' discourses and trying to theorize subjectivity in a way that goes beyond the dualism of individual and society, of psychology and sociology. The relational, or intersubjective, approach to self that originates in object relations psychoanalysis as it emerged in the mid-20th-century UK is central to both of these activities; object of the former and resource for the latter. I explore the paradox that this creates for critical psychology, both epistemological and ontological. In aiming to provide a psycho-social account of self in family relationships, I deploy the radical conceptualisation of intersubjectivity initiated in British object relations theory as a way of going beyond both the individualized self and the neglect of psychological processes in constructionist theorizing subjectivity

The Effects of Altered GABAergic Signaling in Microglia on Hippocampal-cortical Network Activity and Remote Recall

Memory acquisition and encoding are modulated by neural network activity between the hippocampus (HPC) and prefrontal cortex (PFC). Research has shown that neuroimmune defense cells, glia, interact with neurons in both brain regions. However, little is known about glial-neuronal interactions, and how these interactions affect memory network activity and in turn, memory recall. Memory network activity involves a host of cellular excitation and inhibition. The primary neurotransmitter involved in inhibition is γ-aminobutyric acid (GABA), and receptors for this neurotransmitter can also be found on microglia. To better understand glial-neuronal interactions between the HPC and PFC, we utilized a mouse model (GABABFlox) with a knockdown of GABAB receptors on microglia, to alter microglial activity. Our lab utilizes electrophysiological recordings of neuronal activity related to learning and memory in the HPC and PFC. Mice were implanted with 64-channel implants to record from single cells and local field potentials (LFPs) while completing a conditioned place preference task to measure remote recall. Results showed that GABABFlox mice had remote recall (18days) deficits but intact recent recall (1day). We also found that GABABFlox mice had changes in multiple electrophysiological signals associated with memory processing, including: decreased gamma power in the HPC, impairments in theta-gamma comodulation in the cortex, theta and delta hypersynchrony between the HPC and cortex, and fewer sharp-wave ripples in the HPC. These findings suggest that GABAergic signaling on microglia may facilitate neural network systems involved in memory formation and recall, and that alterations in microglia may impair functions necessary for memory formation.https://digitalscholarship.unlv.edu/durep_posters/1066/thumbnail.jp

A Clinical Practice Guideline for the Management of Patients With Degenerative Cervical Myelopathy: Recommendations for Patients With Mild, Moderate, and Severe Disease and Nonmyelopathic Patients With Evidence of Cord Compression.

Study Design: Guideline development. Objectives: The objective of this study is to develop guidelines that outline how to best manage (1) patients with mild, moderate, and severe myelopathy and (2) nonmyelopathic patients with evidence of cord compression with or without clinical symptoms of radiculopathy. Methods: Five systematic reviews of the literature were conducted to synthesize evidence on disease natural history; risk factors of disease progression; the efficacy, effectiveness, and safety of nonoperative and surgical management; the impact of preoperative duration of symptoms and myelopathy severity on treatment outcomes; and the frequency, timing, and predictors of symptom development. A multidisciplinary guideline development group used this information, and their clinical expertise, to develop recommendations for the management of degenerative cervical myelopathy (DCM). Results: Our recommendations were as follows: (1) "We recommend surgical intervention for patients with moderate and severe DCM." (2) "We suggest offering surgical intervention or a supervised trial of structured rehabilitation for patients with mild DCM. If initial nonoperative management is pursued, we recommend operative intervention if there is neurological deterioration and suggest operative intervention if the patient fails to improve." (3) "We suggest not offering prophylactic surgery for non-myelopathic patients with evidence of cervical cord compression without signs or symptoms of radiculopathy. We suggest that these patients be counseled as to potential risks of progression, educated about relevant signs and symptoms of myelopathy, and be followed clinically." (4) "Non-myelopathic patients with cord compression and clinical evidence of radiculopathy with or without electrophysiological confirmation are at a higher risk of developing myelopathy and should be counselled about this risk. We suggest offering either surgical intervention or nonoperative treatment consisting of close serial follow-up or a supervised trial of structured rehabilitation. In the event of myelopathic development, the patient should be managed according to the recommendations above." Conclusions: These guidelines will promote standardization of care for patients with DCM, decrease the heterogeneity of management strategies and encourage clinicians to make evidence-informed decisions

A Clinical Practice Guideline for the Management of Patients With Acute Spinal Cord Injury: Recommendations on Hemodynamic Management

STUDY DESIGN: Clinical practice guideline development following the GRADE process. OBJECTIVES: Hemodynamic management is one of the only available treatment options that likely improves neurologic outcomes in patients with acute traumatic spinal cord injury (SCI). Augmenting mean arterial pressure (MAP) aims to improve blood perfusion and oxygen delivery to the injured spinal cord in order to minimize secondary ischemic damage to neural tissue. The objective of this guideline was to update the 2013 AANS/CNS recommendations on the hemodynamic management of patients with acute traumatic SCI, acknowledging that much has been published in this area since its publication. Specifically, we sought to make recommendations on 1. The range of mean arterial pressure (MAP) to be maintained by identifying an upper and lower MAP limit; 2. The duration of such MAP augmentation; and 3. The choice of vasopressor. Additionally, we sought to make a recommendation on spinal cord perfusion pressure (SCPP) targets. METHODS: A multidisciplinary guideline development group (GDG) was formed that included health care professionals from a wide range of clinical specialities, patient advocates, and individuals living with SCI. The GDG reviewed the 2013 AANS/CNS guidelines and voted on whether each recommendation should be endorsed or updated. A systematic review of the literature, following PRISMA standards and registered in PROSPERO, was conducted to inform the guideline development process and address the following key questions: (i) what are the effects of goal-directed interventions to optimize spinal cord perfusion on extent of neurological recovery and rates of adverse events at any time point of follow-up? and (ii) what are the effects of particular monitoring techniques, perfusion ranges, pharmacological agents, and durations of treatment on extent of neurological recovery and rates of adverse events at any time point of follow-up? The GDG combined the information from this systematic review with their clinical expertise in order to develop recommendations on a MAP target range (specifically an upper and lower limit to target), the optimal duration for MAP augmentation, and the use of vasopressors or inotropes. Using methods outlined by the GRADE working group, recommendations were formulated that considered the balance of benefits and harms, financial impact, acceptability, feasibility and patient preferences. RESULTS: The GDG suggested that MAP should be augmented to at least 75-80 mmHg as the lower limit, but not actively augmented beyond an upper limit of 90-95 mmHg in order to optimize spinal cord perfusion in acute traumatic SCI. The quality of the evidence around the target MAP was very low, and thus the strength of this recommendation is weak. For duration of hemodynamic management, the GDG suggested that MAP be augmented for a duration of 3-7 days. Again, the quality of the evidence around the duration of MAP support was very low, and thus the strength of this recommendation is also weak. The GDG felt that a recommendation on the choice of vasopressor or the use of SCPP targets was not warranted, given the dearth of available evidence. CONCLUSION: We provide new recommendations for blood pressure management after acute SCI that acknowledge the limitations of the current evidence on the relationship between MAP and neurologic recovery. It was felt that the low quality of existing evidence and uncertainty around the relationship between MAP and neurologic recovery justified a greater range of MAP to target, and for a broader range of days post-injury than recommended in previous guidelines. While important knowledge gaps still remain regarding hemodynamic management, these recommendations represent current perspectives on the role of MAP augmentation for acute SCI

A Clinical Practice Guideline for the Management of Patients With Acute Spinal Cord Injury: Recommendations on Hemodynamic Management

STUDY DESIGN Clinical practice guideline development following the GRADE process. OBJECTIVES Hemodynamic management is one of the only available treatment options that likely improves neurologic outcomes in patients with acute traumatic spinal cord injury (SCI). Augmenting mean arterial pressure (MAP) aims to improve blood perfusion and oxygen delivery to the injured spinal cord in order to minimize secondary ischemic damage to neural tissue. The objective of this guideline was to update the 2013 AANS/CNS recommendations on the hemodynamic management of patients with acute traumatic SCI, acknowledging that much has been published in this area since its publication. Specifically, we sought to make recommendations on 1. The range of mean arterial pressure (MAP) to be maintained by identifying an upper and lower MAP limit; 2. The duration of such MAP augmentation; and 3. The choice of vasopressor. Additionally, we sought to make a recommendation on spinal cord perfusion pressure (SCPP) targets. METHODS A multidisciplinary guideline development group (GDG) was formed that included health care professionals from a wide range of clinical specialities, patient advocates, and individuals living with SCI. The GDG reviewed the 2013 AANS/CNS guidelines and voted on whether each recommendation should be endorsed or updated. A systematic review of the literature, following PRISMA standards and registered in PROSPERO, was conducted to inform the guideline development process and address the following key questions: (i) what are the effects of goal-directed interventions to optimize spinal cord perfusion on extent of neurological recovery and rates of adverse events at any time point of follow-up? and (ii) what are the effects of particular monitoring techniques, perfusion ranges, pharmacological agents, and durations of treatment on extent of neurological recovery and rates of adverse events at any time point of follow-up? The GDG combined the information from this systematic review with their clinical expertise in order to develop recommendations on a MAP target range (specifically an upper and lower limit to target), the optimal duration for MAP augmentation, and the use of vasopressors or inotropes. Using methods outlined by the GRADE working group, recommendations were formulated that considered the balance of benefits and harms, financial impact, acceptability, feasibility and patient preferences. RESULTS The GDG suggested that MAP should be augmented to at least 75-80 mmHg as the "lower limit," but not actively augmented beyond an "upper limit" of 90-95 mmHg in order to optimize spinal cord perfusion in acute traumatic SCI. The quality of the evidence around the "target MAP" was very low, and thus the strength of this recommendation is weak. For duration of hemodynamic management, the GDG "suggested" that MAP be augmented for a duration of 3-7 days. Again, the quality of the evidence around the duration of MAP support was very low, and thus the strength of this recommendation is also weak. The GDG felt that a recommendation on the choice of vasopressor or the use of SCPP targets was not warranted, given the dearth of available evidence. CONCLUSION We provide new recommendations for blood pressure management after acute SCI that acknowledge the limitations of the current evidence on the relationship between MAP and neurologic recovery. It was felt that the low quality of existing evidence and uncertainty around the relationship between MAP and neurologic recovery justified a greater range of MAP to target, and for a broader range of days post-injury than recommended in previous guidelines. While important knowledge gaps still remain regarding hemodynamic management, these recommendations represent current perspectives on the role of MAP augmentation for acute SCI