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Sigma-1 Receptors and and their Effects on Mice with rmTBI
Get PDFRepetitive mild traumatic brain (rmTBI) injury is common in contact sports, yet there are no specific treatments to mitigate the potential long-term detrimental effects of such injuries. Retrospective studies have observed athletes in contact sports such as American football, boxing, rugby, soccer, and martial arts have higher rates of Chronic Traumatic Encephalopathy (CTE), mood and behavior disturbance, motor and dementia-related diseases, and other neuropathological diseases. We propose that activation of S1R can mitigate detrimental behavioral and biochemical consequences of repetitive mild head injury in a mouse model. Sigma-1 receptors (S1R) are intracellular chaperone proteins that are involved in numerous cell processes. Among their diverse actions, activation of the S1R has been observed to reduce neurodegeneration in experimental models of stroke, Alzheimer's disease, Parkinson's disease and others. This wide range of effectiveness suggests that targeting S1R could also be beneficial for other neurological injuries including traumatic brain injury. In this short-term study of rmTBI in male mice, we observed only minor behavioral deficits 5 weeks after the last of 7 closed head injuries that may be mitigated by treatment with the prototypical S1R agonist PRE-084. However, PRE-084 itself had basal effects on cognition, making firm conclusions premature. Continued observation of these mice will help to determine whether there are additional long-term effects of the injury mode
Animal model of kidney disease induced by high folic acid
No full textPurpose: The kidney is a vital organ that helps the body eliminate waste and toxic substances and return nutrients and vital substances back into the bloodstream. Kidney disease can be categorized into acute kidney injury (AKI) or chronic kidney disease (CKD). This may be caused by numerous risk factors such as ischemia, sepsis, drug toxicity and drug overdose, exposure to heavy metals, and diabetes. However, the exact prognosis from an AKI to CKD is not fully understood. In addition, approximately 37 million individuals in the United States population currently suffer from CKD. Despite the high prevalence of CKD, information is lacking on our understanding of the pathogenesis of AKI and CKD and there are still no available therapeutics that can be used to combat kidney disease effectively. This highlights an urgent need to further study the pathological mechanisms underlying AKI, CKD, and AKI progression to CKD. In this regard, animal models of kidney disease are imperative.
Methods: This presentation reviews a widely used animal model of kidney disease, which is induced in mice with folic acid (FA). While a low dose of FA is nutritionally favorable, a high dose of FA is toxic to the kidneys. A high dose of FA is injected intra-peritoneally in the mice. Following a brief description of the procedure for disease induction by FA, major mechanisms of FA-induced kidney injury are then reviewed. This includes observing oxidative stress levels, mitochondrial abnormalities such as impaired bioenergetics and mitophagy, ferroptosis, pyroptosis, and increased expression of fibroblast growth factor 23 (FGF23). This is completed to explore possible pathological mechanisms of kidney disease and thereby the efficacy of a variety of therapeutic approaches may be evaluated. These procedural methods required Institutional Animal Care and Use Committee (IACUC) clearance and proper laboratory training to ensure ethical laboratory practices. The presentation will also highlight an overview of how to obtain IACUC clearance and ethical practice certification.
Results: This animal model of inducing high doses of FA can induce both AKI and CKD in mice and therefore can be used to further study AKI to CKD progression.
Conclusion: Given that the animal model is reproducible and can recapitulate human kidney disease phenotypes, it should be useful for both studying the pathological mechanisms of kidney disease and identifying effective therapeutic targets to fight kidney disease.
This presentation is supported by PDRT at UNTHSCThis presentation is supported by PDRT at UNTHS
Significant loss of retinal nerve fibre layer and contrast sensitivity in people with well controlled HIV disease: implications for aging with HIV
Get PDFOBJECTIVE: Antiretroviral therapy has decreased the prevalence of retinal opportunistic infections in people living with HIV (PLWH). However, abnormalities in visual function are evident and may be associated with an early onset of aging in PLWH. In this study, we examined the Retinal Nerve Fibre Layer (RNFL) thickness and visual function in PLWH and HIV non-infected controls in Malaysia. DESIGN: Cross-sectional study. METHODS: Two hundred and two (202) PLWH without retinal opportunistic infection and 182 age-matched, HIV seronegative individuals were enrolled. PLWH were recruited from the Infectious Disease clinic at the University Malaya Medical Centre. Controls were recruited among the hospital staff and community volunteers. RNFL thickness was measured with spectral domain optical coherence tomography (SDOCT). Visual functions include visual acuity using LogMAR chart and contrast sensitivity using Pelli- Robson Chart. RESULTS: All PLWH (mean age 46.1 years +/- 9.9 years) in the study were on ART and 61.2% had a CD4+ T-cell count more than 500 cell/mul. The mean visual acuity was similar between the two groups (LogMAR 0.05 vs. 0.07, p = 0.115). Contrast sensitivity was lower in PLWH compared to HIV seronegative individuals (1.90 vs 1.93, p = 0.032). RNFL thickness was significantly thinner in the temporal quadrant for PLWH compared to controls (68.89 mum vs 74.08 mum, p = 0.001). CONCLUSION: Changes in RNFL thickness and contrast sensitivity were seen in PLWH despite their relatively young age and well controlled HIV disease. The changes reflect structural and functional deficits, and could have long-term implications on their health trajectory.The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This work was supported by the High Impact Research Grants (HIR/MOHE; H-20001-E000001, UM.0000099/HIR.C3). MN was funded by the National Institutes of Health, Fogarty International Center (NIH, FIC) and the National Institute of Neurological Disorders and Stroke (NINDS) (award number D43TW010540)
Challenges in Recruitment of Young Adults Engaging in Sexual Behaviors and Alcohol Use
No full textAbstract
Background
Young adults are at increased risk of negative outcomes, such as sexually transmitted infections and unintended pregnancies, due to alcohol use during sex, condomless sex, and inconsistent contraceptive use. We seek to adapt a brief intervention to address these health behaviors, which requires formative research with young adults engaging in alcohol use during sexual activity. Recruitment of young adults in research studies can be challenging. We examined the recruitment approaches used in this formative study to gain a deeper understanding of the challenges encountered in the recruitment of young adults for a sexual health and alcohol study to improve strategies and overcome obstacles.
Methods
The goal of recruitment for the formative study was to identify eligible participants through a screening survey and invite them to participate in a focus group. Inclusion criteria for the formative study were young adults aged 18-25, not in a monogamous relationship, had inconsistent contraception use or condomless sex, alcohol use during sex in the past month, and had Texas residency. The research team used several recruitment strategies: flyers, emailing community stakeholders to share materials, social media, and monetary incentives. We used the Plan Do Study Act (PDSA) cycle to examine our recruitment approaches in three cycles and reflect on the effectiveness of our recruitment methods. The effectiveness of each cycle was measured by the number of surveys that were completed, the number of eligible participants identified, and the number of resulting focus group participants. The research team reflected on challenges in each cycle.
Results
There were three recruitment cycles identified. Cycle 1 (January-February 2022) primarily focused on distributing flyers and contacting partner organizations to share materials with their clients; challenges included logistics, locations, and the ability to track this strategy. This cycle resulted in 253 surveys completed, 23 eligible potential participants, and 10 focus group participants. Cycle 2 (February-June 2022) incorporated social media advertising (e.g., Twitter, Craigslist, TikTok, and Reddit) to reach large audiences, but introduced issues such as social media platform policies, inauthentic survey results, and increased recruitment costs. This cycle resulted in 475 completed surveys, 10 eligible potential participants, and 1 focus group participant. Cycle 3, where inclusion criteria were broadened to increase the eligible population is preparing to launch to address these challenges.
Conclusions
Many challenges were identified in recruiting young adults engaging in condomless sex, ineffective contraceptive use, and alcohol use during sex to participate in this research study. Each recruitment strategy came with unique issues but a large discrepancy between audiences reached, and successful participants was constant in all strategies. Direct recruitment through partner organizations was effective but required considerable effort to ensure that the study was adequately advertised to potential participants. Social media marketing was effective in reaching large audiences but was complicated by platform advertising policies, false and repeated survey responses, and did not yield a cost-effective number of successful participants. These results suggest that broadening the inclusion criteria may increase the number of eligible participants
Correlation Between Timed Up and Go Test and Neuroimaging in Mexican American and Non-Hispanic Americans with Alzheimer’s Disease
No full textPurpose:
Alzheimer's Disease (AD) is a progressive neurodegenerative disease that causes cognitive and functional impairments. Abnormal amyloid plaque accumulation is known to be specific for AD, demonstrated by previous amyloid Positron Emission Tomography (PET) studies showing abnormal amyloid plagues levels in subjects in the early stages of the disease, not exhibiting clinical manifestations. 1,2 Hispanic Americans are underrepresented in AD research. This study explores the possible relationship between the amyloid plaque level visible on amyloid PET scans and non-specific Physical Performance Tests such as Timed Up and Go (TUG) among Mexican Americans and non-Hispanic white American subjects. Furthermore, this study explores the possible correlation between rising amyloid plaque levels and declining function measured by simple physical performance tests such as TUG in outpatient clinics for AD patients.
Methods:
Data were analyzed on n= 2076 Participants (n= 1037 Non-Hispanic White, n=1039 Hispanic, Mexican American) from the Health and Aging Brain Study- Health Disparities All participants underwent as part of the HABS-HD protocol cognitive testing, functional/medical examination, blood draw, and neuroimaging. Amyloid PET scans (with Neuraceq/florbetaben F18) were conducted with defined regions of intertest (ROIs) included the frontal, anterior/posterior cingulate, lateral parietal, and lateral temporal cortex. All participants completed the Timed UP and Go (TUG) test along with other gait measures as part of the functional examine. The TUG is a measure of functional mobility, higher scores mean worse performance on the measure. Chi-square (Sex) and t-tests (Age, Education, TUG performance) were used to examine differences in demographic characteristics across ethnic groups. Linear regression models were conducted to examine the relationship between Amyloid PET imaging and a functional measure (TUG) and the significance was set at p<0.05
Results:
In our study, we found a statistically significant correlation between TUG time and increased amyloid uptake only in the lateral parietal region in Mexican American subjects (p=0.049). The other ROIs in Mexican American subjects showed no statistically significant correlation between TUG time and increased amyloid uptake. All ROIs in Non-Hispanic Whites showed no statistically significant correlation between TUG time and increased amyloid uptake.
Conclusion:
This study aimed to examine the relationship between physical performance measures (such as the TUG) and amyloid uptake. TUG is a non-specific physical performance measure often used in outpatient offices with older adult patients and is shown to correlate with cognitive decline.3 Using PET scans, we theorized that TUG results might correlate with the amyloid plaque level; however, our results were inconsistent with our initial hypothesis. On the other hand, this study did reveal a correlation between TUG time and increased amyloid uptake (only in the lateral parietal region) with subjects of Mexican descent, therefore; highlighting the importance of exploring ethnic differences in AD research. Finally, this study is limited by a small sample size, and future work with additional samples should help examine the TUG and amyloid uptake relationship and ethnic differences
Contrast-enhanced micro-CT approaches for visualizing musculoskeletal development in neonatal mice
No full textResearch Appreciation Day Award Winner - School of Biomedical Sciences, 2023 Department of Physiology & Anatomy-Structural Anatomy & Rehabilitation Sciences Award - 1st PlaceContrast-enhanced micro-CT approaches for visualizing musculoskeletal development in neonatal mice
Javan A. Stalls, Courtney A. Miller, Jason M. Organ, Emma K. Handler, Lauren A. Gonzales, Kate M. Lesciotto, Rachel A. Menegaz
Purpose: While there are many forms of radiological imaging that can be used to gather anatomical data from biological specimens, computed tomography (CT) imaging has been the gold standard for visualizing dense tissue, such as bone, with detailed resolution. However, this imaging modality is not well suited for soft tissues (muscle, brain, abdominal organs, cartilage, etc.) due to their decreased tissue density. The inability to distinguish between soft tissues in CT scans limits our ability to investigate the bone-muscle interactions known to stimulate and direct bone modeling during early postnatal development. The development of contrast-enhancing staining agents, capable of binding materials to increase their radiodensity, has allowed for more accurate and enhanced visualizations of less dense soft tissues, such as muscle and brain structures. Contrast agents such as iodine have differential affinities for the different soft tissues in the body allowing for easier visualization and segmentation of soft tissues in relation to the skeleton. Previous studies have used contrast-enhanced CT (CE-CT) scanning to analyze early development of mice from prenatal stages to postnatal day 7. However, additional CE-CT imaging during the first three postnatal weeks is needed to understand muscle-bone interactions during critical periods of behavioral development, such as suckling and weaning. The goal of this project is to develop a CE-CT protocol and corresponding anatomical atlas showing the development of skeletal and soft tissue structures in the crania of neonatal mice from birth to weaning.
Methods: Neonatal and preweaning mice (B6C3Fe a/a-Col1a2OIM/J) were euthanized on day of birth (P0), postnatal day 7 (P7), and postnatal day 14 (P14). Ethanol-fixed tissues were submerged in 1.25% iodine in 70% ethanol (I2E) for 2-14 days, with the skin intact in order to preserve cutaneous musculature. Both pre-stained and post-stained tissues were scanned using a MRS CT-80 micro-CT machine (20 µm3 voxel resolution).
Results: Preliminary CE-CT scans following 10 days in an iodine stain present improved visualization of soft tissue (brain structures, cranial muscles, salivary glands) when compared to the baseline bone CT scans.
Conclusion: These scans will be used to develop 3D models of musculoskeletal ontogeny from birth-weaning, providing insights into this critical developmental period. The use of CT contrast agents such as iodine offers new opportunities to investigate the anatomical interactions of bone and muscle during early development, and can be applied to investigate models of both normal growth and pathological disorders affecting musculoskeletal growth
Association of Cancer with Alzheimer's Disease and related Dementias among older adults with chronic pains: TriNetX analysis with Multi-institutional Electronic Health Records
No full textIntroduction
Recent retrospective cohort studies have reported that non-cancer chronic pain, specifically non-cancer pain conditions (NCPCs), are associated with an increased risk of Alzheimer's disease and related dementias (ADRD) in older adults. However, a recent case-control study found that cancer-induced pain had a protective association with ADRD, suggesting that cancer pain's association with ADRD is inconclusive. Therefore, we analyzed the association of cancer with ADRD among older adults with chronic pain.
Methods
We adopted a retrospective cohort analysis. The cohort consisted of older adults with chronic pain in 2016 and 2017. The data used in this study is from the TriNetX Research Network, which provided access to electronic medical records (diagnoses, procedures, medications, and laboratory values) for patients from 64 healthcare organizations (HCOs). A propensity score-matched analysis of cancer and non-cancer patients used age, sex, race/ethnicity, surgery, factors influencing health status and contact with health services; endocrine, nutritional, and metabolic diseases; diseases of the circulatory system; nervous system; digestive system; musculoskeletal system and connective tissue; and mental, behavioral and neurodevelopmental disorders. The outcome variable was ADRD incidence, which occurred at least one year after the first chronic pain diagnosis.
Results
Before matching, among older adults with cancer, there were 212,739 and 465,316 with and without cancer, respectively. The 3-year cumulative incidence of ADRD was 2.97% (N = 6320) in the cancer group and 1.96% (N = 9096) in the non-cancer group. After propensity matching, there were 195289 participants in both groups. The cumulative incidence of ADRD was 2.79% (N = 5457) in the cancer group and 2.62% (N = 5124) in the non-cancer group (Risk Ratio = 1.07, 95% CI: 1.02-1.10). Secondary analysis of ADRD incidence in adults who died did not reveal a significant association between cancer with ADRD.
Conclusion
Our research has found that cancer is not associated with the risk of ADRD among patients with chronic pain. Our study estimates of ADRD incidence are lower than the national rates, suggesting the limitations of electronic health records in capturing true ADRD incidence.
The study's findings must be interpreted in the context of the study's strengths and limitations. For example, data were from 64 HCOs, and the study did not adjust for case-mix or practice differences. In addition, the study is limited to those seeking care in these HCOs and may have missed care obtained outside of these organizations. Thus, our estimates of ADRD incidence are substantially lower than the national ADRD incidence. Nevertheless, the study's strengths are the use of multi-institutional electronic health records, large numbers of cases and controls, and the ability to conduct propensity score-matched analysis with a comprehensive list of risk factors.
Keywords: Dementia, Alzheimer's disease, and Related Disorders, Cancer, Chronic Pain, EH