Medicine and Health Sciences Commons^™

Cognitive Decline Associated With Longitudinal Changes In 24-H Ambulatory Blood Pressure Variability, Jesus D. Melgarejo, Kristina P. Vatcheva, Luis J. Mena, Carlos A. Chavez, Egle Silva, Gustavo E. Calmon, Rosa P. Mavarez, Joseph H. Lee, Joseph D. Terwilliger, Gladys E. Maestre

School of Medicine Publications

Background: Cognitive decline has been associated with variability in blood pressure (BP). However, whether the increment of the BP variability during follow-up precedes cognitive decline remains undocumented. We aimed this study to investigate cognitive decline in relation to longitudinal changes in 24-h reading-to-reading BP variability.

Methods: We conducted an observational longitudinal study that included 717 dementia-free participants from the Maracaibo Aging Study who underwent follow-up assessment in both 24-h ambulatory BP monitoring and cognitive tests between 1998 and 2015. Cognitive domains consisted of selective reminding tests (total, long-term, short-term, and recognition memory) and the Mini-Mental State Examination (MMSE). …

An Innovative Model Using Promotores Or Community Health Workers For Home Based Dementia Care, Neela K. Patel, Cynthia De La Garza- Parker, Angelica Davila, Noe Garza, Monica Goss, Claudia L. Satizabal, Gabriel A. De Erausquin, Gladys E. Maestre, Sudha Seshadri

School of Medicine Publications

Background: Health disparities and issues with trust building and relationship building are prominent in Hispanic and underserved populations in south Texas. Community health workers can play a bridging role with underserved communities and may be essential in improving the quality and value of health care. The Texas Health and Human Services Commission certifies the training Community Health Workers under the label of “promotores”.

Method: Community health workers were integrated into the primary health care team to serve as a bridge between patient/caregiver dyads and the health care team.

Result: Community health workers (CHWs) connected patients to social determinants …

Cognitive Sequealae Of Covid-19 Is Not Predicted By Sars-Cov-2 Variants, Gabriel A. De Erausquin, Jorge Igor Zwir, Heather Snyder, Gabriela Gonzalez-Aleman, Hernan P. Zamponi, Mariana Figueredo-Aguiar, Emiliano Fumagalli, John Blangero, Agustín Yécora,, Fabiana Vaca, Gabriela Kukoc

School of Medicine Publications

Background: The long term sequelae of COVID-19 in older adults are only beginning to be clarified, and its predictors and underlying molecular mechanisms may shed light on the relationship between viral infections and Alzheimer's disease and related dementia.

Method: A prospective cohort of 874 older adult Amerindians from Argentina with COVID-19 illness confirmed by PCR of nasal swabs as well as controls, was established during the first year of the COVID-19 pandemic. We obtained data on the severity of the acute illness, as well as extensive neuropsychiatric and cognitive assessments, neurological exams (including quantitative hyposmia/anosmia), plasma for biomarkers and preliminary …

Preliminary Neurocognitive Finding From A Multi-Site Study Investing Long-Term Neurological Impact Of Covid-19 Using Ultra-High Field 7 Tesla Mri-Based Neuroimaging, Jonika D. Tannous, Farhaan S. Vahidy, Riddhi Patira, Alison M. Luckey, Mitzi M. Gonzales, Akram A. Hosseini, Timothy D. Girard, Tamer Ibrahim, Heidi I.L. Jacobs, Valentina R. Garbarino

School of Medicine Publications

Background: Globally, over six hundred million cases of SARS-CoV-2 have been confirmed. As the number of individuals in recovery rises, examining long-term neurological effects, including cognitive impairment and cerebral microstructural and microvascular changes, has become paramount., We present preliminary cognitive findings from an ongoing multi-site study investigating the long-term neurological impacts of COVID-19 using 7 Tesla MRI-based neuroimaging.

Methods: Across 3 US and 1 UK sites, we identified adult (>=18) COVID-19 survivors (CS) and healthy controls (HC) without significant pre-existing medical, neurological, or psychiatric illness. Using the National Alzheimer’s Coordinating Center (NACC) Uniform Data Set (UDS-3) battery …

Poor Cognition Is Associated With Increased Abundance Of Alistipes And Decreased Abundance Of Clostridium Genera In The Gut, Jazmyn A. Muhammad, Yannick Joel Wadop Ngouongo, Sophia Ramirez, Tiffany F. Kautz, Claudia L. L. Satizabal, Jayandra Jung Himali, Sudha Seshadri, Bernard Fongang

School of Medicine Publications

Background: Brain and gut health are intricately connected via the gut-microbiota-brain axis. Studies have shown that gut dysbiosis is associated with neurodegenerative diseases, including Alzheimer’s disease. However, how cognitive changes affects the gut microbiome structure is currently understudied. We aimed to assess the association between the gut microbiome and global cognitive scores in the Framingham Heart Study (FHS).

Method: Our sample included 1,014 participants (mean age 52, 55% female) of the third generation FHS cohort with available stool samples, cognitive assessments, and no history of dementia or stroke (Table 1).We quantified the gut microbiome composition using 16S rRNA …

Exploration Of The Tumorigenic, Metabolic, And Cognitive Consequences Of Tau Protein Removal, Jennifer M. Erichsen, Valentina R. Garbarino, Anna Rodriguez, Jillian K. Lee, Justin C. Shayne, Timothy C. Orr, Miranda E. Orr

School of Medicine Publications

Background: Tau accumulation causes tauopathies and drives cellular senescence, which can lead to inflammation, neurodegeneration, and cognitive impairment. The association between intracellular tau deposition and pathogenesis has prompted therapeutic strategies that reduce tau expression. However, tau is also critical in microtubule stabilization, synaptic plasticity, and maintaining DNA integrity. We investigated the impact of tau removal on brain cell senescence and associated neurocognitive behaviors in aged tau knockout (Mapt^0/0) and wild type control (Mapt^+/+) mice. We also assessed physical, metabolic, histological, and biochemical outcomes in Mapt^0/0 and Mapt^+/+ mice and in response to …

Dementia And Stroke Risk Associated With Brain Artery Luminal Diameters, Jesus D. Melgarejo, Kursat Gurel, Minghua Liu, Bonnie Levin, Mitchell S.V. Elkind, M. Kamran Ikram, M. Arfan Ikram, Fabrice Crivello, Christophe Tzourio, Zhen-Yu Zhang

School of Medicine Publications

Background: It is unclear whether brain artery diameters measured on conventional T2-weighted brain MRI images relate to dementia and stroke outcomes across distinct populations. We aimed this study to evaluate the association of T2-weighted brain artery luminal diameters with dementia and stroke in three distinct population‑based studies.

Methods: Three longitudinal population-based studies with 8420 adults >40 years old (Northern Manhattan Study [NOMAS] from the United States, and the Rotterdam Study [RS], from the Netherlands, and Three-City, from France) with brain MRI scans obtained between 1999 and 2015. The median follow-up time for clinical events ranged between 7 and …

Hippocampal Subfield Volumes In Covid-19: A Preliminary Multicenter Study Using 7t Mri, Salem Alkateeb, Jinghang Li, Gabriel A. De Erausquin, Monica Goss, Jayandra J. Himali, Karl Li, Rejani R. Nair, Beth E. Snitz, Gowland Penny, Valentina R. Garbarino

School of Medicine Publications

Background: Hippocampal formation atrophy is a well-established imaging biomarker of several neurological diseases, including Alzheimer's disease, temporal lobe epilepsy, and schizophrenia. The hippocampus is divided into subfields that have different functions and vary in sensitivity to different diseases. This study investigates the potential interaction between COVID-19 and the various hippocampus subfields, which may shed light on the long-term neurological consequences of the virus.

Method: We obtained high-resolution T1-weighted (T1w) and T2-weighted (T2w) MRI images using 7T scanners located at three sites in two countries: Pittsburgh (n=14) and Texas (San Antonio and Houston) (n=40) in the USA, and Nottingham, …

Elevated Amyloid-Β And Tau Levels In The Brain Are Associated With A Reduced Abundance Of Neuroprotective Gut Bacteria, Yannick Joel Wadop Ngouongo, Jazmyn A. S. Muhammad, Tiffany F. Kautz, Claudia Satizabal, Jayandra Jung Himali, Sudha Seshadri, Bernard Fongang

School of Medicine Publications

Background: Recent research suggests that differences in the gut microbiome composition may contribute to the pathogenesis of neurological disorders, including Alzheimer's disease (AD). Animal studies have shown that fecal microbiota transplantation reduces amyloid plaques in mouse AD models. However, whether the buildup of Aβ and tau deposits in the brain are associated with shifts in the human gut microbiota composition is understudied.

Method: We used stool specimens and neuropathological measures from 140 middle-aged individuals (Table 1: mean age 56, 54% Female) from the Framingham Heart Study (FHS) to assess the link between the gut microbiome composition and Aβ Positron …

Lower Locus Coeruleus Integrity In Older Covid-19 Survivors: Initial Findings From An International 7t Mri Consortium, Heidi I.L. Jacobs, Tamer Ibrahim, Farhaan S. Vahidy, Timothy D. Girard, Akram A. Hosseini, Salem Alkateeb, Richard Bowtell, Gowland Penny, Mohamad Habes, Valentina R. Garbarino

School of Medicine Publications

Background: The SARS-CoV-2 coronavirus has been associated with structural brain changes, consistent with its neurological manifestations. Recent studies showed a specific predilection for brainstem glial activation and hypometabolism, possibly indicating involvement of the locus coeruleus. The locus coeruleus (LC) modulates many cognitive functions and behaviors and its norepinephrine projections regulate both immune responses and vascular reactivity. We aimed to examine differences in LC integrity between COVID-19 survivors and controls.

Method: Participants are enrolled across 3 US and 1 UK sites using harmonized cognitive and 7T MR-imaging protocols. Here, we analyzed data from 18 participants enrolled at Houston Methodist (12 COVID-19 …

Point-Of-Care Ultrasound For The Diagnosis Of Frequent Cardiovascular Diseases: A Review, Ernesto Calderon Martinez, Edna Diarte, Diana Othon, Leonardo Rodriguez Reyes, Daniel A. Aguirre Cano, Carolina Cantu Navarro, Maria G. Ycaza, David Arriaga Escamilla, Jinal Choudhari, George Michel

School of Medicine Publications

Point-of-care ultrasound (POCUS) has emerged as an indispensable diagnostic tool in cardiology, particularly within the emergency department. This narrative synthesis provides a comprehensive exploration of POCUS applications in cardiovascular diseases, elucidating its multifaceted roles and addressing challenges. The review delves into the technical attributes of POCUS, emphasizing its noninvasive nature, radiation-free qualities, and suitability for non-radiologists. It navigates through educational strategies, stressing the importance of structured programs for the seamless integration of POCUS into clinical practice. Highlighting its efficacy, the synthesis discusses POCUS applications in various scenarios such as dyspnea, chest pain, cardiac arrest, aortic dissection, pericardial effusion, and pulmonary …

Metagenomic Analysis Unveils The Microbial Landscape Of Pancreatic Tumors, Sheema Khan, Goutam Banerjee, Saini Setua, Daleniece Jones, Bhavin Chauhan, Anupam Dhasmana, Pratik Banerjee, Murali M. Yallapu, Stephen Behrman, Subhash C. Chuahan

School of Medicine Publications

The composition of resident microbes in the human body is linked to various diseases and their treatment outcomes. Although studies have identified pancreatic ductal adenocarcinoma (PDAC)-associated bacterial communities in the oral and gut samples, herein, we hypothesize that the prevalence of microbiota in pancreatic tumor tissues is different as compared with their matched adjacent, histologically normal appearing tissues, and these microbial molecular signatures can be highly useful for PDAC diagnosis/prognosis. In this study, we performed comparative profiling of bacterial populations in pancreatic tumors and their respective adjacent normal tissues using 16S rRNA-based metagenomics analysis. This study revealed a higher abundance …

Safety And Immunogenicity Of An In Vivo Muscle Electroporation Delivery System For Dna-Hsp65 Tuberculosis Vaccine In Cynomolgus Monkeys, Monique Ribeiro De Lima, Ana C. Leandro, Andreia Lamoglia De Souza, Marcio Mantuano Barradas, Eric Henrique Roma, Ana Teresa Gomes Fernandes, Gabrielle Galdino-Silva, Joyce Katiuccia M. Ramos Carvalho, Renato Sergio Marchevsky, John L. Vandeberg

School of Medicine Publications

A Bacille Calmette–Guérin (BCG) is still the only licensed vaccine for the prevention of tuberculosis, providing limited protection against Mycobacterium tuberculosis infection in adulthood. New advances in the delivery of DNA vaccines by electroporation have been made in the past decade. We evaluated the safety and immunogenicity of the DNA-hsp65 vaccine administered by intramuscular electroporation (EP) in cynomolgus macaques. Animals received three doses of DNA-hsp65 at 30-day intervals. We demonstrated that intramuscular electroporated DNA-hsp65 vaccine immunization of cynomolgus macaques was safe, and there were no vaccine-related effects on hematological, renal, or hepatic profiles, compared to the pre-vaccination parameters. No tuberculin …

Rare Presentation Of Postpericardiotomy Syndrome After Left Atrial Myxoma Removal, Jessy Feng, Shyama Appareddy, Yaman Gibran, Aryana Garza, Jacqueline Luevano, Gustavo Garcia

School of Medicine Publications

Postpericardiotomy syndrome (PPS) is a known complication of cardiac valve surgery, but it has not been commonly reported as a postoperative complication of cardiac myxoma removal. A 78-year-old female with hypertension and atrial fibrillation presenting with angina was found to have a large left atrial myxoma (7.5 cm × 4.4 cm). The myxoma was resected; however, 1-week postoperation hemoglobin and blood pressure decreased with elevated erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP). Limited transthoracic echocardiogram (TTE) showed moderate pericardial effusion, confirming the diagnosis of PPS. This case highlights the importance of monitoring patients postremoval of myxoma for symptoms of …

The Intersection Of Community Socioeconomic Factors With Gender On Outcomes After Thoracic Aortic Surgery, Ourania Preventza, Elizabeth Akpan-Smart, Katherine K. Simpson, Lorraine D. Cornwell, Hiruni Amarasekara, Susan Y. Green, Subhasis Chatterjee, Scott A. Lemaire, Joseph S. Coselli

School of Medicine Publications

Objective

We evaluated the relationship among community socioeconomic factors (poverty, income, and education), gender, and outcomes in patients who underwent ascending aortic, root, and arch surgery.

Methods

For 2634 consecutive patients, we associated patients' ZIP codes with community socioeconomic factors. The composite adverse outcome comprised death, persistent neurological injury, and renal failure necessitating dialysis at discharge. Multivariable analysis and Kaplan–Meier survival curveswere used. Men and women from the full cohort and from the elective patients were propensity matched.

Results

Median follow-up was 3.6 years (interquartile range, 1.2-9.3). Men lived in areas characterized by less poverty (P = …

From The Borders Edge To The Brink Of Death: A Case Of A Traumatic Pancreatic Injury And Whipple Procedure In The Rio Grande Valley, Valentine S. Alia, Ed W. Alvarado, Edward M. Diaz, Daniel Albo, Roger Galindo

School of Medicine Publications

The traumatic pancreatoduodenectomy, also known as the traumatic Whipple, is a specialized surgical procedure often reserved for extreme cases in which an individual suffers traumatic injuries to the pancreas, duodenum, or periampullary structures. Traditionally, a Whipple procedure is a complex surgery involving the removal of the head of the pancreas, duodenum, and a portion of both the bile duct and stomach, for the management of pancreatic head cancer. In underserved communities where limited access to healthcare is coupled with a higher incidence of trauma, the lack of specialized and supportive care for patients suffering from pancreatic injuries may lead to …

Genome-Wide Significant Risk Loci For Mood Disorders In The Old Order Amish Founder Population, Elizabeth M. Humphries, Kwangmi Ahn, Rachel L. Kember, Fabiana L. Lopes, Evelina Mocci, Juan M. Peralta, John Blangero, David C. Glahn, Fernando S. Goes, Peter P. Zandi

School of Medicine Publications

Genome-wide association studies (GWAS) of mood disorders in large case-control cohorts have identified numerous risk loci, yet pathophysiological mechanisms remain elusive, primarily due to the very small effects of common variants. We sought to discover risk variants with larger effects by conducting a genome-wide association study of mood disorders in a founder population, the Old Order Amish (OOA, n = 1,672). Our analysis revealed four genome-wide significant risk loci, all of which were associated with >2-fold relative risk. Quantitative behavioral and neurocognitive assessments (n = 314) revealed effects of risk variants on sub-clinical depressive symptoms and information processing speed. …

Muc13 Drives Cancer Aggressiveness And Metastasis Through The Yap1-Dependent Pathway, Kyle Doxtater, Manish Tripathi, Radhiki Sekhri, Bilal B. Hafeez, Sheema Khan, Nadeem Zafar, Stephen Behrman, Murali M. Yallapu, Meena Jaggi, Subhash C. Chauhan

School of Medicine Publications

Anchorage-independent survival after intravasation of cancer cells from the primary tumor site represents a critical step in metastasis. Here, we reveal new insights into how MUC13-mediated anoikis resistance, coupled with survival of colorectal tumor cells, leads to distant metastasis. We found that MUC13 targets a potent transcriptional coactivator, YAP1, and drives its nuclear translocation via forming a novel survival complex, which in turn augments the levels of pro-survival and metastasis-associated genes. High expression of MUC13 is correlated well with extensive macrometastasis of colon cancer cells with elevated nuclear YAP1 in physiologically relevant whole animal model systems. Interestingly, a positive correlation …

A Sound Mind In A Sound Body: A Novel Concept Unravelling Heterogeneity Of Depression, Gabor Hullam, Zsofia Gal, Xenia Gonda, Tamas Nagy, Andras Gezsi, Isaac Cano, Sandra Van Der Auwera, Mikko Kuokkanen, Peter Antal, Gabriella Juhasz

School of Medicine Publications

Depression is a highly prevalent and debilitating condition, yet we still lack both in-depth knowledge concerning its etiopathology and sufficiently efficacious treatment options. With approximately one third of patients resistant to currently available antidepressants there is a pressing need for a better understanding of depression, identifying subgroups within the highly heterogeneous illness category and to understand the divergent underlying biology of such subtypes, to help develop and personalise treatments. The TRAJECTOME project aims to address such challenges by (1) identifying depression-related multimorbidity subgroups and shared molecular pathways based on temporal disease profiles from healthcare systems and biobank data using machine …

Whole-Genome Sequencing Uncovers Two Loci For Coronary Artery Calcification And Identifies Arse As A Regulator Of Vascular Calcification, Paul S. De Vries, Matthew P. Conomos, Kuldeep Singh, Christopher J. Nicholson, Deepti Jain, Natalie R. Hasbani, Wanlin Jiang, Sujin Lee, Christian L. Lino Cardenas, Sharon M. Lutz, John Blangero

School of Medicine Publications

Coronary artery calcification (CAC) is a measure of atherosclerosis and a well-established predictor of coronary artery disease (CAD) events. Here we describe a genome-wide association study of CAC in 22,400 participants from multiple ancestral groups. We confirmed associations with four known loci and identified two additional loci associated with CAC (ARSE and MMP16), with evidence of significant associations in replication analyses for both novel loci. Functional assays of ARSE and MMP16 in human vascular smooth muscle cells (VSMCs) demonstrate that ARSE is a promoter of VSMC calcification and VSMC phenotype switching from a contractile to a calcifying or osteogenic phenotype. …

Metabolic Phenotyping Of Bmi To Characterize Cardiometabolic Risk: Evidence From Large Population-Based Cohorts, Habtamu B. Beyene, Corey Giles, Kevin Huynh, Tingting Wang, Michelle Cinel, Natalie A. Mellett, Gavriel Olshansky, Thomas G. Meikle, Gerald F. Watts, John Blangero

School of Medicine Publications

Obesity is a risk factor for type 2 diabetes and cardiovascular disease. However, a substantial proportion of patients with these conditions have a seemingly normal body mass index (BMI). Conversely, not all obese individuals present with metabolic disorders giving rise to the concept of “metabolically healthy obese”. We use lipidomic-based models for BMI to calculate a metabolic BMI score (mBMI) as a measure of metabolic dysregulation associated with obesity. Using the difference between mBMI and BMI (mBMIΔ), we identify individuals with a similar BMI but differing in their metabolic health and disease risk profiles. Exercise and diet associate with mBMIΔ …

Low Dose Intravenous Cangrelor Versus Glycoprotein Iib/Iiia Inhibitors In Endovascular Treatment Of Tandem Lesions, Mouhammad A. Jumaa, Aaron Rodriguez-Calienes, Giana Dawod, Juan Vivanco-Suarez, Ameer E. Hassan, Afshin A. Divani, Marion Oliver, Marc Ribo, Nils Petersen, Michael Abraham

School of Medicine Publications

Objectives

Intravenous (IV) periprocedural antiplatelet therapy (APT) for patients undergoing acute carotid stenting during mechanical thrombectomy (MT) is not fully investigated. We aimed to compare the safety profile of IV low dose cangrelorversus IV glycoprotein IIb/IIIa (GP-IIb/IIIa) inhibitors in patients with acute tandem lesions (TLs).

Materials and methods

We retrospectively identified all cases of periprocedural administration of IV cangrelor or GP-IIb/IIIa inhibitors during acute TLs intervention from a multicenter collaboration. Patients were divided in two groups according to the IV APT regimen at the time of MT procedure: 1) cangrelor and 2) GP-IIb/IIIa inhibitors (tirofiban and eptifibatide). Safety outcomes …

Endovascular Treatment Of Acute Ischemic Stroke Patients With Tandem Lesions: Antegrade Versus Retrograde Approach, Milagros Galecio-Castillo, Michael Abraham, Mudassir Farooqui, Ameer E. Hassan, Afshin A. Divani, Mouhammad A. Jumaa, Marc Ribo, Nils Petersen, Johanna T. Fifi, Wondwossen G. Tekle

School of Medicine Publications

Objective: The optimal technique for treating tandem lesions (TLs) with endovascular therapy is debatable. The authors evaluated the functional, safety, and procedural outcomes of different approaches in a multicenter study.

Methods: Anterior circulation TL patients treated from January 2015 to December 2020 were divided on the basis of antegrade versus retrograde approach and included. The evaluated outcomes were favorable modified Rankin Scale (mRS) score (mRS score 0-2) at 3 months, ordinal shift in mRS score, successful recanalization, excellent recanalization, first-pass effect (FPE), time from groin puncture to successful recanalization, symptomatic intracranial hemorrhage (sICH), and 90-day mortality.

Results: Among 691 patients …

When Two Worlds Collide: A Rare Case Of Multiple Myeloma With Extramedullary Plasmacytoma, Jorge Nadal Bosch, Mario Moya, Samuel Serna, Lee Drinkard, Javier Malcolm

School of Medicine Publications

In this case report, we discuss the presentation, diagnosis, and management of a 67-year-old gentleman with stage II multiple myeloma with concurrent biopsy-proven bone plasmacytoma and why it is important to understand the molecular intricacies of these disorders. We emphasize the critical role of radiology in identifying, characterizing, and managing these lesions. Furthermore, we shed light on the critical differentiation between solitary extramedullary plasmacytoma and multiple myeloma and discuss treatment modalities for both conditions.

A Latent Variable Approach To Assess Dementia In Mexico And The United States: Measurement Invariance And Validation, Joseph Saenz, Christopher Beam, Silvia Mejia-Arango

School of Medicine Publications

Latent dementia indices (LDI) use cognitive and functional data to approximate dementia. Few evaluate the LDI’s utility in cross-national work. This study tests metric measurement invariance of an LDI in the United States and Mexico and evaluates its validity in Mexico. Data included the United States Harmonized Cognitive Assessment Protocol (HCAP, n=3,267), MexCog (n=2,042), and a Mexican clinical validation sample with diagnosed cognitive status (51 cognitively normal, 49 mild cognitive impairment (MCI), and 50 dementia) who received the MexCog battery. The LDI was measured using highly comparable items (13 cognitive and 10 functional). We tested metric measurement invariance of the …

Investigating White Matter Hyperintensities In A Multicenter Covid-19 Study Using 7t Mri, Tales Santini, Oluwatobi F. Adeyemi, Valentina R. Garbarino, Mohamad Habes, Christof Karmonik, Joseph C. Masdeu, Vibhuti N. Patel, Howard J. Aizenstein, Richard Bowtell, Gustavo C. Roman

School of Medicine Publications

Background: Emerging evidence indicates that COVID-19 can negatively impact patient’s brain health (Douaud et al., 2022) (Cecchetti et al., 2022). Common clinical symptoms include brain fog, headaches, difficulty concentrating, and loss of sense of smell or taste. Some studies suggest that SARS-CoV-2 infection can damage the blood brain barrier either directly or through immune-inflammatory mechanisms (Zhang, et al. 2021). White matter hyperintensities (WMH) are imaging biomarkers of brain vascular or inflammatory injury. We investigated the association between severity of COVID-19 infection and burden of white matter hyperintensity volumes within a diverse multi-nation, multi-racial cohort using 7 Tesla (7T) MRI …

Identification Of Genetic Regions Associated With Alzheimer ‘S Disease Blood-Based Biomarkers In Mexican American Families, Marcio A. Almeida

School of Medicine Publications

Background: Dementias are heterogeneous age-associated neurodegenerative disorders generally included in the broad term, Alzheimer’s disease (AD) and related dementias (ADRD). ADRD affects individuals of all ethnicities, but Hispanic individuals show a 1.5-fold higher risk when compared to non-Hispanic whites. Many AD risk biomarkers have been proposed but not much is known about how genetic elements control their expression. We used 2000 genome sequenced Mexican Americans from extended pedigrees to identify genetic regions associated with AD blood-based biomarkers.

Method: A total of 70 Mexican American subjects were diagnosed as ADRD cases (h²= 0.75, p = 2.6×10^-5). We …

Preparation Of Zein-Based Nanoparticles : Nanoprecipitation Versus Microfluidic-Assisted Manufacture, Effects Of Pegylation On Nanoparticle Characteristics And Cellular Uptake By Melanoma Cells, Jitkasem Meewan, Sukrut Somani, Jamal Almowalad, Partha Laskar, Margaret Mullin, Graeme Mackenzie, Swapnil Khadke, Yvonne Perrie, Christine Dufès

School of Medicine Publications

Background: The manufacture of nanoparticles using manual methods is hampered by its challenging scaleup and poor reproducibility. To overcome this issue, the production of zein nanoparticles entrapping a lipophilic drug model, coumarin-6, by using a microfluidic system was assessed in this study. The influence of PEG density and chain length on zein nanoparticle characteristics, as well as their uptake efficacy in melanoma cancer cells, was also evaluated.

Methods: Zein nanoparticles were prepared by both manual and microfluidic approaches to allow comparison between the two processes. PEGylated zein nanoparticles with various PEG densities and chain lengths were produced by …

Type 2 Diabetes Modifies The Association Of Cad Genomic Risk Variants With Subclinical Atherosclerosis, Natalie. R. Hasbani, Kenneth E. Westerman, Soo Heon Kwak, Han Chen, Xihao Li, Daniel Di Corpio, Michael C. Mahaney, Ravi Duggirala, Joanne E. Curran, John Blangero

School of Medicine Publications

Background: Individuals with type 2 diabetes (T2D) have an increased risk of coronary artery disease (CAD), but questions remain about the underlying pathology. Identifying which CAD loci are modified by T2D in the development of subclinical atherosclerosis (coronary artery calcification [CAC], carotid intima-media thickness, or carotid plaque) may improve our understanding of the mechanisms leading to the increased CAD in T2D.

Methods: We compared the common and rare variant associations of known CAD loci from the literature on CAC, carotid intima-media thickness, and carotid plaque in up to 29 670 participants, including up to 24 157 normoglycemic controls and 5513 …

Frailty Index In The Colonias Of The Rio Grande Valley: Health Related Quality Of Life And Resilience, Eron G. Manusov, Vincent P. Diego, Sarah Williams-Blangero

School of Medicine Publications

Background: Frailty is characterized by an accumulation of deficits that lead to vulnerability to adverse health outcomes. The Frailty Index (FI) quantifies frailty by measuring deficits that increase susceptibility to stressors. This study focused on a population of Mexican Americans living in vulnerable communities in the Rio Grande Valley of south Texas. We used a Frailty Index developed based on common health-related data--the Patient Health Questionnaire (PHQ-9) and a Health-related Quality of Life survey (Duke Health Profile). Quality of life, resilience, and frailty are interrelated and influenced by chronic illness, mental illness, poverty, cognitive impairment, and community support.

Methods: We …