Mitochondrial Dynamics and Respiration Within Cells with Increased Open Pore Cytoskeletal Meshes

The cytoskeletal architecture directly affects the morphology, motility, and tensional homeostasis of the cell. In addition, the cytoskeleton is important for mitosis, intracellular traffic, organelle motility, and even cellular respiration. The organelle responsible for a majority of the energy conversion for the cell, the mitochondrion, has a dependence on the cytoskeleton for mobility and function. In previous studies, we established that cytoskeletal inhibitors altered the movement of the mitochondria, their morphology, and their respiration in human dermal fibroblasts. Here, we use this protocol to investigate applicability of power law diffusion to describe mitochondrial locomotion, assessment of rates of fission and fusion in healthy and diseased cells, and differences in mitochondria locomotion in more open networks either in response to cytoskeletal destabilizers or by cell line. We found that mitochondria within fibrosarcoma cells and within fibroblast cells treated with an actin-destabilizing toxin resulted in increased net travel, increased average velocity, and increased diffusion of mitochondria when compared to control fibroblasts. Although the mitochondria within the fibrosarcoma travel further than mitochondria within their healthy counterparts, fibroblasts, the dependence on mitochondria for respiration is much lower with higher rates ofhydrogen peroxide production and was confirmed using the OROBOROS O2K. We also found that rates of fission and fusion of the mitochondria equilibrate despite significant alteration of the cytoskeleton. Rates ranged from 15% to 25%, where the highest rates were observed within the fibrosarcoma cell line. This result is interesting because the fibrosarcoma cell line does not have increased respiration metrics including when compared to fibroblast. Mitochondria travel further, faster, and have an increase in percent mitochondria splitting or joining while not dependent on the mitochondria for a majority of its energy production. This study illustrates the complex interaction between mitochondrial movement and respiration through the disruption of the cytoskeleton

Inter-Rater Reliability of Historical Data Collected by Non-Medical Research Assistants and Physicians in Patients with Acute Abdominal Pain

OBJECTIVES: In many academic emergency departments (ED), physicians are asked to record clinical data for research that may be time consuming and distracting from patient care. We hypothesized that non-medical research assistants (RAs) could obtain historical information from patients with acute abdominal pain as accurately as physicians.METHODS: Prospective comparative study conducted in an academic ED of 29 RAs to 32 resident physicians (RPs) to assess inter-rater reliability in obtaining historical information in abdominal pain patients. Historical features were independently recorded on standardized data forms by a RA and RP blinded to each others' answers. Discrepancies were resolved by a third person (RA) who asked the patient to state the correct answer on a third questionnaire, constituting the "criterion standard." Inter-rater reliability was assessed using kappa statistics (kappa) and percent crude agreement (CrA).RESULTS: Sixty-five patients were enrolled (mean age 43). Of 43 historical variables assessed, the median agreement was moderate (kappa 0.59 [Interquartile range 0.37-0.69]; CrA 85.9%) and varied across data categories: initial pain location (kappa 0.61 [0.59-0.73]; CrA 87.7%), current pain location (kappa 0.60 [0.47-0.67]; CrA 82.8%), past medical history (kappa 0.60 [0.48-0.74]; CrA 93.8%), associated symptoms (kappa 0.38 [0.37-0.74]; CrA 87.7%), and aggravating/alleviating factors (kappa 0.09 [-0.01-0.21]; CrA 61.5%). When there was disagreement between the RP and the RA, the RA more often agreed with the criterion standard (64% [55-71%]) than the RP (36% [29-45%]).CONCLUSION: Non-medical research assistants who focus on clinical research are often more accurate than physicians, who may be distracted by patient care responsibilities, at obtaining historical information from ED patients with abdominal pain

Stories to communicate individual risk for opioid prescriptions for back and kidney stone pain: Protocol for the life storried multicenter randomized clinical trial

© 2020 JMIR Publications. All rights reserved. Background: Prescription opioid misuse in the United States is a devastating public health crisis; many chronic opioid users were originally prescribed this class of medication for acute pain. Video narrative-enhanced risk communication may improve patient outcomes, such as knowledge of opioid risk and opioid use behaviors after an episode of acute pain. Objective: Our objective is to assess the effect of probabilistic and narrative-enhanced opioid risk communication on patient-reported outcomes, including knowledge, opioid use, and patient preferences, for patients who present to emergency departments with back pain and kidney stone pain. Methods: This is a multisite randomized controlled trial. Patients presenting to the acute care facilities of four geographically and ethnically diverse US hospital centers with acute renal colic pain or musculoskeletal back and/or neck pain are eligible for this randomized controlled trial. A control group of patients receiving general risk information is compared to two intervention groups: One receiving the risk information sheet plus an individualized, visual probabilistic Opioid Risk Tool (ORT) and another receiving the risk information sheet plus a video narrative-enhanced probabilistic ORT. We will study the effect of probabilistic and narrative-enhanced opioid risk communication on the following: Risk awareness and recall at 14 days postenrollment, reduced use or preferences for opioids after the emergency department episode, and alignment with patient preference and provider prescription. To assess these outcomes, we administer baseline patient surveys during acute care admission and follow-up surveys at predetermined times during the 3 months after discharge. Results: A total of 1302 patients were enrolled over 24 months. The mean age of the participants was 40 years (SD 14), 692 out of 1302 (53.15%) were female, 556 out of 1302 (42.70%) were White, 498 out of 1302 (38.25%) were Black, 1002 out of 1302 (76.96%) had back pain, and 334 out of 1302 (25.65%) were at medium or high risk. Demographics and ORT scores were equally distributed across arms. Conclusions: This study seeks to assess the potential clinical role of narrative-enhanced, risk-informed communication for acute pain management in acute care settings. This paper outlines the protocol used to implement the study and highlights crucial methodological, statistical, and stakeholder involvement as well as dissemination considerations

Communication Biophysics

Contains reports on five research projects.National Institutes of Health (Grant 5 RO1 NB-05462-02)National Aeronautics and Space Administration (Grant NsG-496)National Science Foundation (Grant GP-2495)National Institutes of Health (Grant MH-04737-05

Genetic association between APOE*4 and neuropsychiatric symptoms in patients with probable Alzheimer's disease is dependent on the psychosis phenotype

Background: Neuropsychiatric symptoms such as psychosis are prevalent in patients with probable Alzheimer's disease (AD) and are associated with increased morbidity and mortality. Because these disabling symptoms are generally not well tolerated by caregivers, patients with these symptoms tend to be institutionalized earlier than patients without them. The identification of protective and risk factors for neuropsychiatric symptoms in AD would facilitate the development of more specific treatments for these symptoms and thereby decrease morbidity and mortality in AD. The E4 allele of the apolipoprotein E (APOE) gene is a well-documented risk factor for the development of AD. However, genetic association studies of the APOE 4 allele and BPS in AD have produced conflicting findings.Methods: This study investigates the association between APOE and neuropsychiatric symptoms in a large sample of clinically well-characterized subjects with probable AD (n=790) who were systematically evaluated using the Consortium to Establish a Registry for Alzheimer's Disease (CERAD) Behavioral Rating Scale for Dementia (BRSD).Results: Our study found that hallucinations were significantly more likely to occur in subjects with no APOΕ4 alleles than in subjects with two Ε4 alleles (15% of subjects and 5% of subjects, respectively; p=.0066), whereas there was no association between the occurrence of delusions, aberrant motor behavior, or agitation and the number of Ε4 alleles. However, 94% of the subjects with hallucinations also had delusions (D+H).Conclusion: These findings suggest that in AD the Ε4 allele is differentially associated with D+H but not delusions alone. This is consistent with the hypothesis that distinct psychotic subphenotypes may be associated with the APOE allele. © 2012 Christie et al.; licensee BioMed Central Ltd

Hypopituitarism caused by blast-related mTBI may result in PTSD-like symptoms

Recent studies in civilian populations have found the prevalence of hypopituitarism as a result of head injuries from all causes to be between 25 and 50%. However, the neuroendocrine effects of concussion, or mild traumatic brain injury (mTBI) due to explosive blasts have received relatively little attention. Blast-related mTBI is the most common injury sustained by U.S. troops deployed to Iraq or Afghanistan. Approximately 20% of returning service members have experienced one or more blast-related concussions. Posttraumatic hypopituitarism (PTHP) has been shown to result in several symptoms that overlap considerably with those of PTSD. These include fatigue, depression, sexual dysfunction, anxiety, social isolation, and detrimental effects on sleep, learning and memory, body composition, and quality of life. We are investigating the prevalence of PTHP in two groups of Veterans of deployment to Iraq or Afghanistan. Members of the TBI group sustained at least one blast-related mTBI; members of the deployment control (DC) group experienced similar extreme conditions but did not experience a blast concussion. We conducted screening for growth hormone deficiency (GHD), hypogonadism, thyroid deficiency, and secondary adrenal insufficiency (sAI) by measuring basal blood samples and by testing for GHD and sAI with the glucagon stimulation test. Eighteen of 44 (36.4%) TBI group participants and seven of 32 (15.6%) DC group participants screened positive for pituitary hormone deficits. GHD and sAI were observed most frequently. We used behavioral self-reports and cognitive testing to examine symptom prevalence. Veterans with TBI and pituitary dysfunction endorsed more severe and/or frequent symptoms than those in the TBI group without hypopituitarism or the DC group. These findings and observations suggest that screening for pituitary dysfunction after head injuries holds promise for not only recognizing appropriate treatment options that might not otherwise be considered, but also facilitating recovery and rehabilitation of these service members.DoD CDMRP Concept Award PT090753 and VA RR&D Merit Award to CWW; Geriatric Research, Education and Clinical Center, and the Research and Development Service of the VA Puget Sound Health Care System; the VA Northwest Network Mental Illness Research, Education and Clinical Center; and the University of Washington Alzheimerʼs Disease Research Center NIA AG05136