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Articles 1 - 30 of 122
Full-Text Articles in Medicine and Health Sciences
Evidence For A Bioelectrical Marker Of Insulin Resistance In Premenopausal Women: Membrane Capacitance, Valene E. Garr Barry
Evidence For A Bioelectrical Marker Of Insulin Resistance In Premenopausal Women: Membrane Capacitance, Valene E. Garr Barry
All ETDs from UAB
Insulin resistance (IR) is associated with poor metabolic and reproductive outcomes among premenopausal women. Early identification of women with IR might mitigate these outcomes. However, clinically suitable methods to identify women with IR are unavailable due to high cost, high patient burden, or limited reliability. The objective was to examine a bioimpedance-based approach to identifying women with IR using membrane capacitance (CM). CM is a measure of cell membrane health and function, which is independently associated with IR and may be a suitable predictor. We validated the association of CM with IR and established the clinical utility of CM as …
Tau-Sh3 Interactions And Alzheimer's Disease, Jonathan Roth
Tau-Sh3 Interactions And Alzheimer's Disease, Jonathan Roth
All ETDs from UAB
Alzheimer’s disease (AD) is the most common neurodegenerative disorder worldwide, and its impact will increase with an aging population. It is characterized by dementia associated with accumulation of extracellular amyloid-β (Aβ) plaques, intracellular hyperphosphorylated Tau tangles, and neurodegeneration. Additionally, network hyperexcitability occurs early in AD and likely contributes to disease pathogenesis. Current therapies provide minor delay of disease progression at best, so it is imperative to develop novel therapeutic approaches to prevent and treat AD. As Tau pathology correlates better with cognitive function than Aβ pathology and Tau reduction prevents Aβ-induced dysfunction in preclinical models, targeting Tau is a growing …
Understanding The Role Of Biomechanics In Ovarian Cancer Biology, Alba Martinez Diaz
Understanding The Role Of Biomechanics In Ovarian Cancer Biology, Alba Martinez Diaz
All ETDs from UAB
Mechanical forces including compression, tension, and shear stress are increasingly implicated as instigators of tumor progression. Understanding how mechanobiology drives ovarian cancer is critical to identifying potential therapies. The effect of shear stress is beginning to be studied in ovarian cancer due to the presence of ascites in the peritoneal cavity that prompts tumor cells detachment and implantation in secondary sites. Therefore, mechanical cues are present within the peritoneal cavity. A growing ovarian tumor mass also experiences compressive and tensile forces, although their participation in tumor progression still remains unclear. Additionally, there is a specific lack of incorporation of mechanobiology …
An Exploration Of The Manifestation Of Parentification Among Young Carers Of Persons With Huntington’S Disease, Bailey Hendricks
An Exploration Of The Manifestation Of Parentification Among Young Carers Of Persons With Huntington’S Disease, Bailey Hendricks
All ETDs from UAB
Due to the progressive deterioration of motor, cognitive, and psychological function experienced by individuals diagnosed with Huntington’s disease, there is the potential for children in the home to adopt a caregiving role. These young carers typically serve as informal, secondary caregivers, providing multifaceted, extended care without any lessening of typical family, home, or school/work-related responsibilities. In time, this role may result in parentification, a type of role reversal with both positive and negative outcomes for the child. A secondary analysis of qualitative data of the experiences of children who have a parent with Huntington’s disease was conducted. Transcripts of qualitative …
Identifying Novel Therapeutics And Therapeutic Entry Points For The Treatment Of Duchenne Muscular Dystrophy Through Regulation Of Gene Expression, Rylie Maria Hightower
Identifying Novel Therapeutics And Therapeutic Entry Points For The Treatment Of Duchenne Muscular Dystrophy Through Regulation Of Gene Expression, Rylie Maria Hightower
All ETDs from UAB
My graduate research has primarily focused on genetic and epigenetic modifiers of Duchenne muscular dystrophy and understanding how those modifiers can be used as novel therapeutic entry points for treatment. A vast array of promising therapeutic strategies is being explored outside the realm of directly targeting dystrophin deficiency. This is primarily due to the lack of successful clinical trials that have demonstrated the ability to benefit a significant number of DMD patients. Here, I have expanded the field’s understanding of using the regulation of gene expression as a way to target dystrophin-deficiency associated pathology through, 1) therapeutic treatment of a …
Local Priming Of Long-Lived Tcf1+ Memory Cd8+ T Cell Responses In The Spleen During Influenza Virus Infection By Lung Derived Migratory Dendritic Cells, Meagan Jenkins
All ETDs from UAB
Initiation of CD8+ T cell responses to influenza virus infection requires the trafficking of activated lung-migratory dendritic cells (mDCs) from the lung into the lung-draining mediastinal LN (med-LN). As such, when mDCs are absent from the lungs or are unable to migrate into the med-LN, T cell responses are severely compromised, and the mortality rate increases in mouse models of influenza infection. Importantly, it is generally considered that mDCs die shortly after reaching the med-LN. Thus, the current paradigm suggests that priming of all subsets of influenza-specific CD8+ T cell responses by mDCs takes place solely in the med-LN. Recent …
Rural And Urban Differences In Vegetable And Fruit Consumption Among Older Cancer Survivors In The Deep South: An Exploratory Cross-Sectional Study, Harleen Kaur
All ETDs from UAB
Background: Rural Americans have poorer overall health and physical functioning than their urban counterparts. A varied diet, rich in vegetable and fruit (V&F) consumption may improve health; however, little is known about rural-urban differences in V&F consumption, especially in older cancer survivors. Objective: To assess differences in V&F consumption among older cancer survivors residing in urban- and rural-designated areas, and explore whether differences exist by sex, race, and cancer type. Design: This was a cross-sectional secondary analysis. Participants/setting: Screening data from the Harvest for Health trial was obtained on 731 Medicare-eligible cancer survivors across Alabama. Main outcome measures: V&F consumption …
Actual And Perceived Balance Abilities While Performing Tasks That Challenge Balance In Older Adults And Individuals With Parkinson's Disease., Jutaluk Kongsuk
Actual And Perceived Balance Abilities While Performing Tasks That Challenge Balance In Older Adults And Individuals With Parkinson's Disease., Jutaluk Kongsuk
All ETDs from UAB
Walking is a fundamental activity for one to interact effectively with one’s environment. Walking in the community often requires both a wide range and constant modification of walking speed. Decreased walking capacity, that is the maximum speed that a person can physically achieve, results in a decline in both functional mobility and personal independence, contributing to decreased community participation among individuals whose walking is impaired. The most common test of walking speed (i.e., overground comfortable and maximum walking speed) may not reflect the full capacity of individuals to regulate gait control. Whereas walking with progressively increasing treadmill speeds allows researchers …
Heads Or Tails? Structural Studies Of Host Interaction And Molecular Piracy In Bacteriophages, James Lewis Kizziah
Heads Or Tails? Structural Studies Of Host Interaction And Molecular Piracy In Bacteriophages, James Lewis Kizziah
All ETDs from UAB
Staphylococcus aureus is an opportunistic human pathogen dependent mainly on bacteriophages (phages) for dissemination of the virulence factors that contribute to its pathogenicity. Most phages have double-stranded DNA (dsDNA) genomes which are packaged into protein capsids attached to tails of varying morphology to form their complete virion structures. S. aureus pathogenicity islands (SaPIs) are highly specialized mobile genetic elements that encode various virulence factors and have been named molecular pirates for their ability to parasitize certain helper phages. SaPI1 is capable of hijacking virions constructed by the helper phage 80α, partly by altering the size of the capsid to only …
The Association Between Medicaid Expansion, Medicaid Disproportionate Share Payments And The Financial Performance Of Safety Net Hospitals, Jon Law
All ETDs from UAB
Safety Net Hospitals (SNHs) provide necessary emergency and acute care to all individuals, regardless of their ability to pay for health care. Medicaid Expansion and Disproportionate Share (DSH) payments are two Medicaid programs that may mitigate the financial vulnerability of SNH’s. Some assert that Medicaid Expansion, as part of the Patient and Affordable Care Act (ACA), may provide financial relief for SNHs. It offers payment mechanisms for millions of uninsured individuals. DSH expenditures per capita for each state vary widely. There is some likelihood that SNHs in some states may benefit greater than others. The study was framed within the …
Chemical, Physical, And Antibacterial Properties Of Contemporary Pulp Capping Materials, Yu-Yin Lin
Chemical, Physical, And Antibacterial Properties Of Contemporary Pulp Capping Materials, Yu-Yin Lin
All ETDs from UAB
The purpose of this project was to compare the chemical, physical, and antibacterial properties of right contemporary direct pulp capping materials. The material categories included in this study were calcium hydroxide (Dycal, Lime-Lite and Ultra-Blend plus), calcium silicate (MTA Angelus, Biodentine, TheraCal LC), calcium aluminate (Ceramir Protect LC), and resin ionomer (Bio-Cap). Calcium release and pH changes were measured via a calcium ion-selective electrode (Vernier Company) and pH sensor (Vernier Company) respectively, after specimens were immersed in 36.8oC deionized water for 1, 7, 28 and 90 days. Water solubility was calculated with weight loss of the specimens from 0 to …
The Role Of Race, Sex, And Place In The Association Of Diabetes And Cardiovascular Disease, Gargya Malla
The Role Of Race, Sex, And Place In The Association Of Diabetes And Cardiovascular Disease, Gargya Malla
All ETDs from UAB
Cardiovascular disease risk is higher among adult with diabetes than those without diabetes. This increase in risk may vary by race, sex, and neighborhood characteristics. Recent US data showed a resurgence in stroke and coronary heart disease (CHD) among adults with diabetes, and an increase in heart failure (HF) mortality. Therefore, this dissertation investigated how cardiovascular disease risk may vary by race, sex, and neighborhood characteristics for adults across the glycemic spectrum.Data from the REasons for Geographic and Racial Differences in Stroke (REGARDS) study, an ongoing prospective cohort of 30,239 Black and White adults age 45 years at baseline (2003-07) …
Omics Discovery For Cardiometabolic Traits In African Americans, Bre Ashanti Minniefield
Omics Discovery For Cardiometabolic Traits In African Americans, Bre Ashanti Minniefield
All ETDs from UAB
Research shows African Americans are more likely to suffer from a chronic disease compared to other American populations. Due to the fact that African Americans are extremely underrepresented within human health research, the potential biological causes of the racial/ethnic differences are not well understood. Some of these health differences may be due to genomic variations within either the mitochondrial genome, nuclear genome, or both. To aid the revolution of inclusive human health research, we examined genomic factors related to cardiometabolic diseases in African Americans.African Americans have the highest prevalence of hypertension compared to all other American populations. With the majority …
Alternative Splicing Of Anxa7 Dictates Receptor Tyrosine Kinase Fates In Glioblastoma, Sindhu Nair
Alternative Splicing Of Anxa7 Dictates Receptor Tyrosine Kinase Fates In Glioblastoma, Sindhu Nair
All ETDs from UAB
Alternative splicing (AS) is a tightly regulated process essential for lineage specification in complex tissues like the brain. Dysregulated splicing in glioblastoma (GBM) is a mechanism exploited by tumor cells to retain or splice out exons consequently rewiring isoform-specific protein interactions to sustain tumor phenotypes. Receptor tyrosine kinases (RTK) amplifications are frequent events in GBM driving tumor growth and progression and are key targets for chemotherapy. However, RTK targeting in GBM has achieved limited success predominantly due to adaptive mechanisms of resistance in a constantly evolving tumor microenvironment. Clonal populations and crosstalk between RTKs sustain heterogeneity within a tumor leading …
Evaluation Of Antimicrobial Effect Of Licorice Extrcat Agiasnt Oral Microorganisms, Roshanak Rastegar
Evaluation Of Antimicrobial Effect Of Licorice Extrcat Agiasnt Oral Microorganisms, Roshanak Rastegar
All ETDs from UAB
Introduction: The causative factors of dental caries have been studied for many years, however, preventing the formation of dental caries remains an elusive task. Microorganisms have been the focal point of numerous studies as a prime cariogenic factor. Streptococcus mutans and Candida albicans have been frequently co-isolated from dental biofilm in patients with early childhood caries (ECC) and studies have demonstrated the synergistic effects of these two microorganisms in promoting tooth demineralization. Acid and glucan production, which are two virulence factors produced by S. mutans that mediate biofilm formation and tooth decay, have been shown to be promoted during co-colonization …
The Impact Posttraumatic Stress Disorde On The Developing Brain And Educational Considerations, Kristen N. Buford
The Impact Posttraumatic Stress Disorde On The Developing Brain And Educational Considerations, Kristen N. Buford
All ETDs from UAB
About 90% of the population will experience a traumatic event within their lifetime, but only a small percentage of this population will develop Posttraumatic Stress Disorder (PTSD). PTSD has a profound impact on the developing brain, specifically neural circuits that support fear learning, memory, and regulation processes. Child PTSD is associated with structural and functional abnormalities in the prefrontal cortex, hippocampus, amygdala, and anterior cingulate cortex, which effect emotion regulation, memory, threat processing, and fear extinction. These neurological effects on the developing brain have serious implications for academic achievement, but with institutional interventions, schools have been able to effectively reduce …
Statistical Methods For Evaluating Confounding In Nutritional Epidemiology: Examining The Association Of Dietary Measures And Incident Type 2 Diabetes, Stephanie E. Tison
Statistical Methods For Evaluating Confounding In Nutritional Epidemiology: Examining The Association Of Dietary Measures And Incident Type 2 Diabetes, Stephanie E. Tison
All ETDs from UAB
Nutrition is a key factor in the development of noncommunicable diseases (NCDs) such as cardiovascular disease, diabetes, obesity, and cancer, which are continuing to increase globally. Research on dietary patterns is crucial for informing what aspects of diet are most critical for preventing and possibly reversing chronic disease. Dietary patterns focus on the types of food that are consumed which reflects the complexity and cultural aspects of diet rather than focusing on a single food or nutrient. Observational cohort studies are able to observe typical dietary intake and thus better reflect the real association between diet and chronic disease. In …
Sialylation As A Novel Mechanism Of Radiation Resistance In Rectal Cancer, Mary Smithson
Sialylation As A Novel Mechanism Of Radiation Resistance In Rectal Cancer, Mary Smithson
All ETDs from UAB
Locally advanced rectal cancer is treated with chemoradiotherapy followed by surgery. Most patients do not have a complete response to chemoradiotherapy, and the resistance mechanisms are poorly understood. We investigated the role of ST6GAL-1 in therapeutic resistance. ST6GAL-1 is a sialytransferase that adds the negatively charged sugar, sialic acid (Sia), to cell surface proteins in the Golgi altering their function. We hypothesized that ST6GAL-1 mediates resistance to chemoradiation in rectal cancer by inhibiting apoptosis. Patient derived xenograft (PDX) and organoid models of rectal cancer as well as rectal cancer cell lines SW837 and SW620 were assessed for ST6GAL-1 protein with …
Maxillary And Mandibular Expansion Treatment With Invisalign First: A Retrospective Study Of Virtual Prediction Versus Clinical Outcomes, Laura Constanza Rey Londono
Maxillary And Mandibular Expansion Treatment With Invisalign First: A Retrospective Study Of Virtual Prediction Versus Clinical Outcomes, Laura Constanza Rey Londono
All ETDs from UAB
Introduction: The purpose of this retrospective study is to evaluate the maxillary and mandibular expansion achieved with Invisalign First (Align Technology, San Jose, CA) in growing children. Methods: Clinical stereolithography (STL) models of 32 patients in the mixed dentition stage, treated with the Invisalign First, were extracted from the ClinCheck software and analyzed in Dolphin imaging (version 11.95 Premium, Chatsworth, Calif) at three timepoints: T1 (initial records), T2 (virtual outcome prediction), and T3 (achieved outcome). The recorded measurements included: upper and lower primary intercanine and permanent intermolar width, upper and lower primary intercanine and permanent intermolar gingival width, upper arch …
The Role Of Cd38 In Anti-Tumor Immunity And Tumor Immune Evasion, Panpan Yuan
The Role Of Cd38 In Anti-Tumor Immunity And Tumor Immune Evasion, Panpan Yuan
All ETDs from UAB
CD38 is a multifunctional protein that is expressed in many immune cells, modulating NAD metabolism, inflammation and oxidative stress. Recent studies suggest that CD38 is also implicated in tumor immunosuppression. However, the role of CD38 in anti-tumor immunity and tumor immune evasion, and mechanisms involved, are still unclear. We hypothesized that CD38 expression by immune cells constricts T cell-mediated anti-tumor immune responses and promotes tumor cell immune evasion. We investigated whether mice lacking CD38 (CD38-/-) had impaired tumor growth in subcutaneous, intraperitoneal and intravenous syngeneic tumor models. CD38-/- mice showed no difference in subcutaneous B16 melanoma tumor growth and pulmonary …
Evaluation Of The Bonding Strength Between Different Materials And Resin Cement Used For Cementing A Fixed Complete Prosthesis, Vinita Pankaj Ved
Evaluation Of The Bonding Strength Between Different Materials And Resin Cement Used For Cementing A Fixed Complete Prosthesis, Vinita Pankaj Ved
All ETDs from UAB
Statement of Problem: When a situation of full-arch edentulism is observed, CAD-CAM designed prosthesis have improved properties in comparison to conventional fixed dentures. Long term longevity of the prosthesis includes not only strength of the framework, but also enhanced bonding strength between the framework and implant coping. Purpose: To investigate the bonding strength between different polymer materials used for a monolithic metal-free fixed hybrid denture luted to Ti-Base using the push-out strength test. Materials and Methods: The experimental design consists of 20 specimens for each group, with a total of 7 groups (total = 140). The materials used in the …
The Association Between Sleep Disturbance And The Neurocognitive Function In Pediatric Sickle Cell Disease, Tiffany D. Tucker
The Association Between Sleep Disturbance And The Neurocognitive Function In Pediatric Sickle Cell Disease, Tiffany D. Tucker
All ETDs from UAB
Background and objective: Youth with sickle cell disease (SCD) without neurological complications continue to be at increased risk of neurocognitive difficulties. Nocturnal hypoxemia is associated with neurocognitive outcomes and has been identified as a chronic complication in youth with SCD. The objective of this study was to assess the relationship between sleep disturbances and neurocognitive functioning in youth with SCD, while taking into account demographics and socioeconomic factors. Methods: Youth with SCD were identified through retrospective chart review who underwent a standardized polysomnography (PSG) and completed a neuropsychological testing battery to assess cognitive skills, including verbal comprehension, working memory, processing …
Experience-Dependent Plasticitiy Of Functional Connectivity In Human Visual Cortex Following Central Vision Loss, Leland Lanelle Fleming
Experience-Dependent Plasticitiy Of Functional Connectivity In Human Visual Cortex Following Central Vision Loss, Leland Lanelle Fleming
All ETDs from UAB
The human brain is shaped by a dynamic interplay between innate factors and life experiences. Neuroscience has long grappled with understanding this relationship, particularly with regard to how changes in experience impact the brain during adulthood. This question is especially important in the context of macular degeneration, a disease that causes significant visual impairment and drastically alters day-to-day visual experiences for individuals afflicted by the disease. Specifically, people with macular degeneration lose the ability to use vision in the center of the visual field, the region of the retina with the highest spatial resolution. Subsequently, these individuals must rely on …
Challenges For Nurse Anesthetists Re-Entering Practice Following Substance Use Disorder Treatment, T'Anya Marye Carter
Challenges For Nurse Anesthetists Re-Entering Practice Following Substance Use Disorder Treatment, T'Anya Marye Carter
All ETDs from UAB
Substance use disorder (SUD) is a persistent, relapsing condition that is present in approximately 10% of anesthesia providers, who, compared to other healthcare providers, face a greater risk of developing an SUD by virtue of constant access to medications. The ability of Certified Registered Nurse Anesthetists (CRNAs) to obtain employment or maintain employment after treatment for SUD treatment is not well documented. CRNAs in recovery from SUD in the United States experience challenges when attempting to return to work following treatment for SUD for reasons yet to be identified. The purpose of this qualitative multiple-case study was to explore the …
Pain-Related Injustice Appraisal And Chronic Low Back Pain Among Arabs In The United States, Albatool Homoud Alnojeidi
Pain-Related Injustice Appraisal And Chronic Low Back Pain Among Arabs In The United States, Albatool Homoud Alnojeidi
All ETDs from UAB
Pain-related injustice appraisal has emerged as a psychosocial predictor of deleterious chronic low back pain (CLBP) outcomes. The appraisal is defined as the individual’s perception regarding the magnitude and irreparability of pain-related loss and suffering, externalized blame, and unfairness. Research in diverse samples revealed racial differences in pain-related injustice appraisal, suggesting that it may reflect broader racial/ethnic, sociocultural, and socioeconomic factors. This agrees with theories recognizing the role of ethnic and cultural characteristics in ethnic minorities’ health. Despite global data showing that Arabs represent the population with the second-highest prevalence of CLBP worldwide, a reliable characterization of CLBP among Arabs …
Neonatal Murine Cytomegalovirus Infection Disrupts Synapse Remodeling During Development, Jerome Moulden
Neonatal Murine Cytomegalovirus Infection Disrupts Synapse Remodeling During Development, Jerome Moulden
All ETDs from UAB
Human cytomegalovirus (HCMV) is a complex double stranded DNA betaherpesvirus. Its linear DNA in enclosed in an icosahedral capsid, and has a genome size of about 230kb and encodes about 170 genes. Primary infection with HCMV lead to a lifelong persistent infection. HCMV can also be transmitted across the placenta and infect the developing fetus leading to infection of the newborn infant, an infection which is commonly described as congenital HCMV infection. In the United States, the prevalence of congenital HCMV infection is between 0.2-1.2%. Approximately 5-15% of these newborn infants will develop long-term neurological damage resulting, motor disorder, cognition …
Identifying Factors To Inform The Development Of Adaptive Interventions For Increasing Physical Activity Behavior Among People With Multiple Schlerosis, Yumi Kim
All ETDs from UAB
People with multiple sclerosis (MS) can benefit from physical activity, specifically exercise, for the management of disease symptoms, including walking impairments, fatigue, and depression, and improvements in quality of life. However, people with MS do not engage in adequate amounts of physical activity for the accrual of health benefits. Researchers have focused on the delivery of exercise training and behavioral interventions to improve levels of physical activity in MS. To date, there is an emerging body of research supporting the efficacy of these interventions for increasing and potentially sustaining physical activity behavior in people with MS. Yet, people with MS …
Patterns Of Medication Adherence In Glaucoma, Shervonne Poleon
Patterns Of Medication Adherence In Glaucoma, Shervonne Poleon
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Over 60 million persons globally are affected by primary open angle glaucoma (POAG)—an optic neuropathy characterized by distinctive patterns of vision loss. Glaucoma is a leading cause of irreversible blindness worldwide, and eye drops that delay vision loss are a common treatment modality. In glaucoma, the proportion of patients with good adherence to recommended therapy is reported to be low. High treatment cost, forgetfulness, and regimen complexity have been identified as key determinants of poor adherence. However, addressing these factors in the clinic is not as simple, as patient and provider values and priorities may differ. Without concordance, it can …
Production And Purification Of Titanium-45 For Imaging Of Psma+ Prostate Cancer, Ivis Francis Chaple
Production And Purification Of Titanium-45 For Imaging Of Psma+ Prostate Cancer, Ivis Francis Chaple
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Positron Emission Tomography (PET) has revolutionized the world of molecular imaging, increasing the potential for improved diagnosis and characterization of various disease states, including cancer. Molecular biology has afforded the knowledge that each type of cancer cell is different, and these differences can be leveraged to develop methods for targeting these cells for imaging or therapy, as well as understanding of other characteristics. Due to the increased diversity in available targets, there has been an equal need to develop new agents used to image these receptors. Radioisotopes with varying halflives, chemical and nuclear properties have been studied in recent years …
Analysing The Contribution Of Snare-Dependent Exocytosis From Astrocytes To Huntinton's Disease Pathogenesis Using The Bachd Mouse Model, Annesha C. King
Analysing The Contribution Of Snare-Dependent Exocytosis From Astrocytes To Huntinton's Disease Pathogenesis Using The Bachd Mouse Model, Annesha C. King
All ETDs from UAB
Huntington’s disease (HD) is a dominantly inherited neurodegenerative disease caused by a polyglutamine expansion in the huntingtin protein. Multiple studies have indicated the importance of mutant huntingtin (mHTT) in astrocytes to HD pathogenesis. Increased extracellular glutamate levels were observed after evoking SNARE-dependent exocytosis from cultured mHTT expressing astrocytes. To determine whether astrocytic SNARE-dependent exocytosis contributed to behavioral and neuropathological changes in vivo, we crossed BACHD mice to dominant negative SNARE (dnSNARE) mice and analyzed behavioral and neuropathological phenotypes. First, we found that reduc-ing astrocytic SNARE-dependent exocytosis had differential effects on the psychiatric-like and motor phenotypes observed in BACHD mice where …