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School of Medicine Publications

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Full-Text Articles in Medicine and Health Sciences

Whole Genome Sequence Data From Captive Baboons Implicate Rbfox1 In Epileptic Seizure Risk, Mark Z. Kos, Melanie A. Carless, Lucy Blondell, M. Michelle Leland, Koyle D. Knape, Harald Hh Goring, Charles A. Szabo Aug 2021

Whole Genome Sequence Data From Captive Baboons Implicate Rbfox1 In Epileptic Seizure Risk, Mark Z. Kos, Melanie A. Carless, Lucy Blondell, M. Michelle Leland, Koyle D. Knape, Harald Hh Goring, Charles A. Szabo

School of Medicine Publications

In this study, we investigate the genetic determinants that underlie epilepsy in a captive baboon pedigree and evaluate the potential suitability of this non-human primate model for understanding the genetic etiology of human epilepsy. Archived whole-genome sequence data were analyzed using both a candidate gene approach that targeted variants in baboon homologs of 19 genes (n = 20,881 SNPs) previously implicated in genetic generalized epilepsy (GGE) and a more agnostic approach that examined protein-altering mutations genome-wide as assessed by snpEff (n = 36,169). Measured genotype association tests for baboon cases of epileptic seizure were performed using SOLAR, as …


Frailty Index In The Colonias On The Us-Mexico Border: A Special Report, Eron G. Manusov, Carolina Gomez De Ziegler, Vincent P. Diego, Gerardo Munoz-Monaco, Sarah Williams-Blangero Aug 2021

Frailty Index In The Colonias On The Us-Mexico Border: A Special Report, Eron G. Manusov, Carolina Gomez De Ziegler, Vincent P. Diego, Gerardo Munoz-Monaco, Sarah Williams-Blangero

School of Medicine Publications

Frailty is the age-related decline in well-being. The Frailty index (FI) measures the accumulation of health deficits and reflects biopsychosocial and cultural determinants of well-being. Frailty is measured as a static phenotype or as a Frailty Index comprising a ratio of suffered health deficits and total deficits. We report a Frailty Index calculated from routinely measured clinical variables gathered from residents of two Colonias (neighborhoods) in South Texas. A Colonia is a predominantly Hispanic, economically distressed, unincorporated neighborhood. We analyzed retrospective data from 894 patients that live in two Colonias located on the Texas-Mexico border. We calculated the FI with …


Population Sequencing Data Reveal A Compendium Of Mutational Processes In Human Germline, Vladimir B. Seplyarskiy, Ruslan A. Soldatov, Evan Koch, Ryan J. Mcginty, Jakob M. Goldmann, Ryan D. Hernandez, Kathleen Barnes, Adolfo Correa, Esteban G. Burchard, John Blangero Aug 2021

Population Sequencing Data Reveal A Compendium Of Mutational Processes In Human Germline, Vladimir B. Seplyarskiy, Ruslan A. Soldatov, Evan Koch, Ryan J. Mcginty, Jakob M. Goldmann, Ryan D. Hernandez, Kathleen Barnes, Adolfo Correa, Esteban G. Burchard, John Blangero

School of Medicine Publications

Mechanistic processes underlying human germline mutations remain largely unknown.Variation in mutation rate and spectra along the genome is informative about the biological mechanisms. We statistically decompose this variation into separate processes using a blind source separation technique. The analysis of a large-scale whole genome sequencing dataset (TOPMed) reveals nine processes that explain the variation in mutation properties between loci. Seven of these processes lend themselves to a biological interpretation. One process is driven by bulky DNA lesions that resolve asymmetrically with respect to transcription and replication. Two processes independently track direction of replication fork and replication timing. We identify a …


Milk Exosomes: Nature's Abundant Nanoplatform For Theranostic Applications, Benilde Adriano, Nycol Cotto, Neeraj Chauhan, Meena Jaggi, Subhash C. Chauhan, Murali M. Yallapu Aug 2021

Milk Exosomes: Nature's Abundant Nanoplatform For Theranostic Applications, Benilde Adriano, Nycol Cotto, Neeraj Chauhan, Meena Jaggi, Subhash C. Chauhan, Murali M. Yallapu

School of Medicine Publications

Exosomes are a unique subpopulation of naturally occurring extracellular vesicles which are smaller intracellular membrane nanoparticle vesicles. Exosomes have proven to be excellent nanocarriers for carrying lipids, proteins, mRNAs, non-coding RNAs, and DNAs, and disseminating long-distance intercellular communications in various biological processes. Among various cell-line or biological fluid derived exosomes, milk exosomes are abundant in nature and exhibit many nanocarrier characteristics favorable for theranostic applications. To be an effective delivery carrier for their clinical translation, exosomes must inbuilt loading, release, targeting, and imaging/tracking characteristics. Considering the unmet gaps of milk exosomes in theranostic technology it is essential to focus the …


Prevalence Of Dementia In Latin America: A Collaborative Study Of Population-Based Cohorts, Ricardo Nitrini, Cássio M. C. Bottino, Cecilia Albala, Nilton Santos Custodio Capuñay, Carlos Ketzoian, Juan J. Llibre Rodriguez, Gladys E. Maestre, Ana Teresa A. Ramos-Cerqueira Jul 2021

Prevalence Of Dementia In Latin America: A Collaborative Study Of Population-Based Cohorts, Ricardo Nitrini, Cássio M. C. Bottino, Cecilia Albala, Nilton Santos Custodio Capuñay, Carlos Ketzoian, Juan J. Llibre Rodriguez, Gladys E. Maestre, Ana Teresa A. Ramos-Cerqueira

School of Medicine Publications

Background:

Dementia is becoming a major public health problem in Latin America (LA), yet epidemiological information on dementia remains scarce in this region. This study analyzes data from epidemiological studies on the prevalence of dementia in LA and compares the prevalence of dementia and its causes across countries in LA and attempts to clarify differences from those of developed regions of the world.

Methods:

A database search for population studies on rates of dementia in LA was performed. Abstracts were also included in the search. Authors of the publications were invited to participate in this collaborative study by sharing missing …


A Prospective Cross-Sectional Study Of Tuberculosis In Elderly Hispanics Reveals That Bcg Vaccination At Birth Is Protective Whereas Diabetes Is Not A Risk Factor, Julia M. Scordo, Genesis P. Aguillón-Durán, Doris Ayala, Ana P. Quirino-Cerrillo, Eminé Rodriguez-Reyna, Francisco Mora-Guzmán Dr, Jose A. Caso, Eder Ledezma-Campos, Larry Schlesinger, Jordi B. Torrelles, Blanca I. Restrepo Jul 2021

A Prospective Cross-Sectional Study Of Tuberculosis In Elderly Hispanics Reveals That Bcg Vaccination At Birth Is Protective Whereas Diabetes Is Not A Risk Factor, Julia M. Scordo, Genesis P. Aguillón-Durán, Doris Ayala, Ana P. Quirino-Cerrillo, Eminé Rodriguez-Reyna, Francisco Mora-Guzmán Dr, Jose A. Caso, Eder Ledezma-Campos, Larry Schlesinger, Jordi B. Torrelles, Blanca I. Restrepo

School of Medicine Publications

Background: Aging increases the risk of tuberculosis (TB) and its adverse outcomes, but most studies are based on secondary analyses, and few are in Hispanics. Diabetes is a risk factor for TB in adults, but its contribution in the elderly is unknown. We aimed to identify the role of diabetes and other risk factors for TB in elderly Hispanics.

Methods: Cross-sectional study among newly-diagnosed TB patients, recent contacts (ReC), or community controls (CoC) totaling 646 participants, including 183 elderly (>60 years; 43 TB, 80 ReC, 60 CoC) and 463 adults (18 to 50 years; 80 TB, 301 ReC and …


The Power Of Interdependence: Linking Health Systems, Communities, And Health Professions Educational Programs To Better Meet The Needs Of Patients And Populations, Richard N. Van Eck, Heidi L. Gullett, Sara M. Lamb, Helene J. Krouse, Lauren Mazzurco, Onelia G. Lage, Joy H. Lewis, Kimberly D. Lomis Jul 2021

The Power Of Interdependence: Linking Health Systems, Communities, And Health Professions Educational Programs To Better Meet The Needs Of Patients And Populations, Richard N. Van Eck, Heidi L. Gullett, Sara M. Lamb, Helene J. Krouse, Lauren Mazzurco, Onelia G. Lage, Joy H. Lewis, Kimberly D. Lomis

School of Medicine Publications

Promoting optimal health outcomes for diverse patients and populations requires the acknowledgement and strengthening of interdependent relationships between health professions education programs, health systems, and the communities they serve. Educational programs must recognize their role as integral components of a larger system. Educators must strive to break down silos and synergize efforts to foster a health care workforce positioned for collaborative, equitable, community-oriented practice. Sharing interprofessional and interinstitutional strategies can foster wide propagation of educational innovation while accommodating local contexts. This paper outlines how member schools of the American Medical Association Accelerating Change in Medical Education Consortium leveraged interdependence to …


Phenotypic And Functional Signatures Of Peripheral Blood And Spleen Compartments Of Cynomolgus Macaques Infected With T. Cruzi: Associations With Cardiac Histopathological Characteristics, Renato Sathler-Avelar, Danielle Marquete Vitelli-Avelar, Armanda Moreira Mattoso-Barbosa, Marcelo Antônio Pascoal-Xavier, Silvana Maria Elói-Santos, Ismael Artur Da Costa-Rocha, Andréa Teixeira-Carvalho, Edward J. Dick Jr, Jane F. Vandeberg, John L. Vandeberg, Olindo Assis Martins-Filho Jul 2021

Phenotypic And Functional Signatures Of Peripheral Blood And Spleen Compartments Of Cynomolgus Macaques Infected With T. Cruzi: Associations With Cardiac Histopathological Characteristics, Renato Sathler-Avelar, Danielle Marquete Vitelli-Avelar, Armanda Moreira Mattoso-Barbosa, Marcelo Antônio Pascoal-Xavier, Silvana Maria Elói-Santos, Ismael Artur Da Costa-Rocha, Andréa Teixeira-Carvalho, Edward J. Dick Jr, Jane F. Vandeberg, John L. Vandeberg, Olindo Assis Martins-Filho

School of Medicine Publications

We performed a detailed analysis of immunophenotypic features of circulating leukocytes and spleen cells from cynomolgus macaques that had been naturally infected with Trypanosoma cruzi, identifying their unique and shared characteristics in relation to cardiac histopathological lesion status. T. cruzi-infected macaques were categorized into three groups: asymptomatic [CCC(-)], with mild chronic chagasic cardiopathy [CCC(+)], or with moderate chronic chagasic cardiopathy [CCC(++)]. Our findings demonstrated significant differences in innate and adaptive immunity cells of the peripheral blood and spleen compartments, by comparison with non-infected controls. CCC(+) and CCC(++) hosts exhibited decreased frequencies of monocytes, NK and NKT-cell subsets in …


Stress And Molecular Drivers For Cancer Progression: A Longstanding Hypothesis, Justin Wendel, A. Verma, Vijian Dhevan, Subhash C. Chauhan, Manish Tripathi Jul 2021

Stress And Molecular Drivers For Cancer Progression: A Longstanding Hypothesis, Justin Wendel, A. Verma, Vijian Dhevan, Subhash C. Chauhan, Manish Tripathi

School of Medicine Publications

Stress management is becoming very important part of cancer patient care. Chronic stressors lead to boost tumorigenesis and promote cancer development, recurrence, and drug resistant leading to poor health outcomes. The Hypothalamic-Pituitary-Adrenal (HPA) axis, which is activated by stress, also regulates Hypothalamic-Pituitary-Thyroid (HPT) axis. Stress related changes in immune function and inflammatory response also leads to reduced immune surveillance resulting in tumorigenesis. This article explores the hormonal axis impacted by stress and how chronic stress can lead to poor outcome of a cancer patient.


Prevalence And Incidence Of Possible Vascular Dementia Among Mexican Older Adults: Analysis Of The Mexican Health And Aging Study, Sara G. Yeverino-Castro, Silvia Mejia-Arango, Alberto José Mimenza-Alvarado, Carlos Cantú-Brito, José A. Avila-Funes, Sara G. Aguilar-Navarro Jul 2021

Prevalence And Incidence Of Possible Vascular Dementia Among Mexican Older Adults: Analysis Of The Mexican Health And Aging Study, Sara G. Yeverino-Castro, Silvia Mejia-Arango, Alberto José Mimenza-Alvarado, Carlos Cantú-Brito, José A. Avila-Funes, Sara G. Aguilar-Navarro

School of Medicine Publications

Introduction: Vascular dementia is the second most common cause of dementia. Physical disability and cognitive impairment due to stroke are conditions that considerably affect quality of life. We estimated the prevalence and incidence of possible vascular dementia (PVD) in older adults using data from the Mexican Health and Aging Study (MHAS 2012 and 2015 waves).

Methods: The MHAS is a representative longitudinal cohort study of Mexican adults aged ≥50 years. Data from 14, 893 participants from the 2012 cohort and 14,154 from the 2015 cohort were analyzed to estimate the prevalence and incidence of PVD. Self-respondents with history of stroke …


Association Of Hiv-1 Infection And Antiretroviral Therapy With Type 2 Diabetes In The Hispanic Population Of The Rio Grande Valley, Texas, Usa, Juan Carlos Lopez Alvarenga, Dora A. Martinez, Alvaro Diaz-Badillo, Liza D. Morales, Rector Arya, Christopher Jenkinson, Joanne E. Curran, John Blangero, Ravi Duggirala, Srinivas Mummidi, Ruben D. Martinez Jul 2021

Association Of Hiv-1 Infection And Antiretroviral Therapy With Type 2 Diabetes In The Hispanic Population Of The Rio Grande Valley, Texas, Usa, Juan Carlos Lopez Alvarenga, Dora A. Martinez, Alvaro Diaz-Badillo, Liza D. Morales, Rector Arya, Christopher Jenkinson, Joanne E. Curran, John Blangero, Ravi Duggirala, Srinivas Mummidi, Ruben D. Martinez

School of Medicine Publications

The Rio Grande Valley (RGV) in South Texas has one of the highest prevalence of obesity and type 2 diabetes (T2D) in the United States (US). We report for the first time the T2D prevalence in persons with HIV (PWH) in the RGV and the interrelationship between T2D, cardiometabolic risk factors, HIV-related indices, and antiretroviral therapies (ART). The PWH in this study received medical care at Valley AIDS Council (VAC) clinic sites located in Harlingen and McAllen, Texas. Henceforth, this cohort will be referred to as Valley AIDS Council Cohort (VACC). Cross-sectional analyses were conducted using retrospective data obtained from …


Global Impact Of Covid-19 On Stroke Care, Raul G. Nogueira, Mohamad Abdalkader, Muhammad M. Qureshi, Michael Frankel, Ossama Y. Mansour, Hiroshi Yamagami, Zhongming Qiu, Mehdi Farhoudi, James E. Siegler, Ameer E. Hassan Jul 2021

Global Impact Of Covid-19 On Stroke Care, Raul G. Nogueira, Mohamad Abdalkader, Muhammad M. Qureshi, Michael Frankel, Ossama Y. Mansour, Hiroshi Yamagami, Zhongming Qiu, Mehdi Farhoudi, James E. Siegler, Ameer E. Hassan

School of Medicine Publications

Background

The COVID-19 pandemic led to profound changes in the organization of health care systems worldwide.

Aims

We sought to measure the global impact of the COVID-19 pandemic on the volumes for mechanical thrombectomy, stroke, and intracranial hemorrhage hospitalizations over a three-month period at the height of the pandemic (1 March–31 May 2020) compared with two control three-month periods (immediately preceding and one year prior).

Methods

Retrospective, observational, international study, across 6 continents, 40 countries, and 187 comprehensive stroke centers. The diagnoses were identified by their ICD-10 codes and/or classifications in stroke databases at participating centers.

Results

The hospitalization volumes …


A Challenging Case Of Refractory Biliary Leak In A Patient With Hydatid Liver Disease, Aws Alameri, Mohammed Alkhero, Alfarooq Alshaikhli, Abbas Alshami, James Saca Jul 2021

A Challenging Case Of Refractory Biliary Leak In A Patient With Hydatid Liver Disease, Aws Alameri, Mohammed Alkhero, Alfarooq Alshaikhli, Abbas Alshami, James Saca

School of Medicine Publications

Hydatid liver disease (HLD) is the most common form of hydatid disease, and it is caused by a zoonotic infection with a tape worm. It is endemic mostly in sheep-farming countries and rare in the United States. Liver involvement is usually asymptomatic, but symptoms develop upon growth of the cyst leading to many complications, most common of which is intra-biliary rupture, and less likely biliary obstruction. Diagnosis is clinical, serologic and radiologic. Therapeutic approaches to HLD include surgery, anthelminthic medications and medico-surgical procedures. Here we present a case of HLD that presented in advanced stage leading to grave consequences, complicated …


Implications Of Helminth Immunomodulation On Covid-19 Co-Infections, Nathalie Chacon, Leonor Chacin-Bonilla, Italo M. Cesar Jul 2021

Implications Of Helminth Immunomodulation On Covid-19 Co-Infections, Nathalie Chacon, Leonor Chacin-Bonilla, Italo M. Cesar

School of Medicine Publications

Coronavirus disease 2019 (COVID-19) and helminths infections can be in a synergistic epidemic in developing and suburban areas of industrialized countries. The coinfected hosts will derive a parasite-specific Th2 innate and adaptive immune response with CD4+ T cells, eosinophils, interleukin-4, interleukin-5, and interleukin-10. In the early stages of severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) infection, virus-specific Th1 cytotoxic CD8+ T cell, interleukin-6, interferon-γ, and interleukin-27 by lung are keys in controlling viral replication in the lung epithelial cells and limiting the pathology to other organs, like the intestine. CD4+ and CD8+ T cells are associated with protective immunity …


Endothelial Senescence And Chronic Fatigue Syndrome, A Covid-19 Based Hypothesis, Adonis Sfera, Carolina Osorio, Carlos M. Zapata Martín Del Campo, Shaniah Pereida, Jose Campo Maldonado, Zisis Kozlakidis Jun 2021

Endothelial Senescence And Chronic Fatigue Syndrome, A Covid-19 Based Hypothesis, Adonis Sfera, Carolina Osorio, Carlos M. Zapata Martín Del Campo, Shaniah Pereida, Jose Campo Maldonado, Zisis Kozlakidis

School of Medicine Publications

Myalgic encephalomyelitis/chronic fatigue syndrome is a serious illness of unknown etiology, characterized by debilitating exhaustion, memory impairment, pain and sleep abnormalities. Viral infections are believed to initiate the pathogenesis of this syndrome although the definite proof remains elusive. With the unfolding of COVID-19 pandemic, the interest in this condition has resurfaced as excessive tiredness, a major complaint of patients infected with the SARS-CoV-2 virus, often lingers for a long time, resulting in disability, and poor life quality. In a previous article, we hypothesized that COVID-19-upregulated angiotensin II triggered premature endothelial cell senescence, disrupting the intestinal and blood brain barriers. Here, …


Neuropsychiatric Symptoms Among Hispanics: Results Of The Maracaibo Aging Study, Mario Gil, Ney Alliey-Rodriguez, Juan Carlos Lopez Alvarenga, Vincent P. Diego, Ciro Gaona, Ledys Mata, Rosa V. Pirela, Carlos A. Chavez, Gabriel A. De Erausquin, Jesus D. Melgarejo, Gladys E. Maestre Jun 2021

Neuropsychiatric Symptoms Among Hispanics: Results Of The Maracaibo Aging Study, Mario Gil, Ney Alliey-Rodriguez, Juan Carlos Lopez Alvarenga, Vincent P. Diego, Ciro Gaona, Ledys Mata, Rosa V. Pirela, Carlos A. Chavez, Gabriel A. De Erausquin, Jesus D. Melgarejo, Gladys E. Maestre

School of Medicine Publications

Background:

Neuropsychiatric symptoms play an important role in diagnosing and clinical follow-up of cognitive impairment and dementia.

Objective:

We investigated the relationship between neuropsychiatric symptoms, cognitive impairment, and dementia in Hispanics.

Methods:

We included 529 participants (age ≥40 years) from the Maracaibo Aging Study with standardized neuropsychiatric assessments, including the Neuropsychiatric Inventory (NPI). Based on the Clinical Dementia Rating and the Mini-Mental State Examination scores, participants’ cognitive status was categorized into normal cognition, mild/moderate, and severe cognitive impairment. Diagnosis of dementia was established in a consensus conference. Statistical analyses included multivariable logistic regression models and area under the curve (AUC). …


Covid-19 And Delayed Cerebral Ischemia—More In Common Than First Meets The Eye, Pervinder Bhogal, Levansri Makalanda, Ameer E. Hassan, Dave Fiorella, Tommy Andersson, Muhammad Ahmad, Hansjörg Bäzner, Ounali Jaffer, Hans Henkes Jun 2021

Covid-19 And Delayed Cerebral Ischemia—More In Common Than First Meets The Eye, Pervinder Bhogal, Levansri Makalanda, Ameer E. Hassan, Dave Fiorella, Tommy Andersson, Muhammad Ahmad, Hansjörg Bäzner, Ounali Jaffer, Hans Henkes

School of Medicine Publications

Since the arrival of the global COVID-19 pandemic scientists around the world have been working to understand the pathological mechanisms resulting from infection. There has gradually been an understanding that COVID-19 triggers a widespread endotheliopathy and that this can result in a widespread thrombosis and in particular a microthrombosis. The mechanisms involved in the microthrombosis are not confined to infection and there is evidence that patients with aneurysmal sub-arachnoid haemorrhage (SAH) also suffer from an endotheliopathy and microthrombosis. In this article we attempt to shed light on similarities in the underlying processes involved in both diseases and suggest potential treatment …


Genome Sequencing Unveils A Regulatory Landscape Of Platelet Reactivity, Ali R. Keramati, Ming-Huei Chen, Lisa R. Yanek, Arunoday Bhan, John Blangero, Benjamin A. T. Rodriguez, Joanne E. Curran, Michael Mahaney, Harald Hh Goring, Ravi Duggirala Jun 2021

Genome Sequencing Unveils A Regulatory Landscape Of Platelet Reactivity, Ali R. Keramati, Ming-Huei Chen, Lisa R. Yanek, Arunoday Bhan, John Blangero, Benjamin A. T. Rodriguez, Joanne E. Curran, Michael Mahaney, Harald Hh Goring, Ravi Duggirala

School of Medicine Publications

Platelet aggregation at the site of atherosclerotic vascular injury is the underlying pathophysiology of myocardial infarction and stroke. To build upon prior GWAS, here we report on 16 loci identified through a whole genome sequencing (WGS) approach in 3,855 NHLBI Trans-Omics for Precision Medicine (TOPMed) participants deeply phenotyped for platelet aggregation. We identify the RGS18 locus, which encodes a myeloerythroid lineage-specific regulator of G-protein signaling that co-localizes with expression quantitative trait loci (eQTL) signatures for RGS18 expression in platelets. Gene-based approaches implicate the SVEP1 gene, a known contributor of coronary artery disease risk. Sentinel variants at RGS18 and PEAR1 are …


4-1bbl As A Mediator Of Cross-Talk Between Innate, Adaptive, And Regulatory Immunity Against Cancer, Alejandra G. Martinez-Perez, Jose J. Perez-Trujillo, Rodolfo Garza-Morales, Maria J. Loera-Arias, Odila Saucedo-Cardenas, Aracely Garcia-Garcia, Humberto Rodriguez-Rocha, Roberto Montes-De-Oca-Luna Jun 2021

4-1bbl As A Mediator Of Cross-Talk Between Innate, Adaptive, And Regulatory Immunity Against Cancer, Alejandra G. Martinez-Perez, Jose J. Perez-Trujillo, Rodolfo Garza-Morales, Maria J. Loera-Arias, Odila Saucedo-Cardenas, Aracely Garcia-Garcia, Humberto Rodriguez-Rocha, Roberto Montes-De-Oca-Luna

School of Medicine Publications

The ability of tumor cells to evade the immune system is one of the main challenges we confront in the fight against cancer. Multiple strategies have been developed to counteract this situation, including the use of immunostimulant molecules that play a key role in the anti-tumor immune response. Such a response needs to be tumor-specific to cause as little damage as possible to healthy cells and also to track and eliminate disseminated tumor cells. Therefore, the combination of immunostimulant molecules and tumor-associated antigens has been implemented as an antitumor therapy strategy to eliminate the main obstacles confronted in conventional therapies. …


Determinants Of Penetrance And Variable Expressivity In Monogenic Metabolic Conditions Across 77,184 Exomes, Julia K. Goodrich, Moriel Singer-Berk, Rachel Son, Abigail Sveden, Jordan Wood, Eleina England, Joanne B. Cole, John Blangero, Ben Weisburd, Ravi Duggirala Jun 2021

Determinants Of Penetrance And Variable Expressivity In Monogenic Metabolic Conditions Across 77,184 Exomes, Julia K. Goodrich, Moriel Singer-Berk, Rachel Son, Abigail Sveden, Jordan Wood, Eleina England, Joanne B. Cole, John Blangero, Ben Weisburd, Ravi Duggirala

School of Medicine Publications

Hundreds of thousands of genetic variants have been reported to cause severe monogenic diseases, but the probability that a variant carrier develops the disease (termed penetrance) is unknown for virtually all of them. Additionally, the clinical utility of common polygenetic variation remains uncertain. Using exome sequencing from 77,184 adult individuals (38,618 multi-ancestral individuals from a type 2 diabetes case-control study and 38,566 participants from the UK Biobank, for whom genotype array data were also available), we apply clinical standard-of-care gene variant curation for eight monogenic metabolic conditions. Rare variants causing monogenic diabetes and dyslipidemias display effect sizes significantly larger than …


Overemphasis Of Usmle And Its Potential Impact On Diversity In Otolaryngology, Pompeyo R. Quesada, Roberto N. N. Solis, Macaulay A. Ojeaga Jr., Nuen T. Yang, Sandra L. Taylor, Rodney C, Diaz Jun 2021

Overemphasis Of Usmle And Its Potential Impact On Diversity In Otolaryngology, Pompeyo R. Quesada, Roberto N. N. Solis, Macaulay A. Ojeaga Jr., Nuen T. Yang, Sandra L. Taylor, Rodney C, Diaz

School of Medicine Publications

Objective: Applicant demographics during the 2019-2020 residency cycle were evaluated to determine if strict utilization of United States Medical Licensing Examination (USMLE) scores in applicant selection could lead to a restriction in diversity.

Study design: Cross-sectional study.

Setting: Otolaryngology residency applicants to a single institution.

Methods: A total of 381 applicants were analyzed by age, gender, applicant type, race/ethnicity, USMLE scores, permanent zip code, and graduating medical school.

Results: Among applicants, 37% were women; 9% were ≥30 years of age; 12% were underrepresented minorities (URMs); 71% to 81% had above-average socioeconomic surrogate markers; 22% were from a top 25 US …


Gwas Significance Thresholds For Deep Phenotyping Studies Can Depend Upon Minor Allele Frequencies And Sample Size, Huma Asif, Ney Alliey-Rodriguez, Sarah Keedy, Carol A. Tamminga, John A. Sweeney Jun 2021

Gwas Significance Thresholds For Deep Phenotyping Studies Can Depend Upon Minor Allele Frequencies And Sample Size, Huma Asif, Ney Alliey-Rodriguez, Sarah Keedy, Carol A. Tamminga, John A. Sweeney

School of Medicine Publications

An important issue affecting genome-wide association studies with deep phenotyping (multiple correlated phenotypes) is determining the suitable family-wise significance threshold. Straightforward family-wise correction (Bonferroni) of p < 0.05 for 4.3 million genotypes and 335 phenotypes would give a threshold of p < 3.46E−11. This would be too conservative because it assumes all tests are independent. The effective number of tests, both phenotypic and genotypic, must be adjusted for the correlations between them. Spectral decomposition of the phenotype matrix and LD-based correction of the number of tested SNPs are currently used to determine an effective number of tests. In this paper, we compare these calculated estimates with permutation-determined family-wise significance thresholds. Permutations are performed by shuffling individual IDs of the genotype vector for this dataset, to preserve correlation of phenotypes. Our results demonstrate that the permutation threshold is influenced by minor allele frequency (MAF) of the SNPs, and by the number of individuals tested. For the more common SNPs (MAF > 0.1), the permutation family-wise threshold was in close agreement with spectral decomposition methods. However, for less common SNPs (0.05 < MAF ≤ 0.1), the permutation threshold calculated over all SNPs was off by orders of magnitude. This applies to the number of individuals studied (here 777) but not to very much larger numbers. Based on these findings, we propose that the threshold to find a particular level of family-wise significance may need to be established using separate permutations of the actual data for several MAF bins.


Nanotechnology Synergised Immunoengineering For Cancer, Deepak S. Chauhan, Anupam Dhasmana, Partha Laskar, Rajendra Prasad, Nishant K. Jain, Rohit Srivastava, Meena Jaggi, Subhash C. Chauhan, Murali M. Yallapu Jun 2021

Nanotechnology Synergised Immunoengineering For Cancer, Deepak S. Chauhan, Anupam Dhasmana, Partha Laskar, Rajendra Prasad, Nishant K. Jain, Rohit Srivastava, Meena Jaggi, Subhash C. Chauhan, Murali M. Yallapu

School of Medicine Publications

Novel strategies modulating the immune system yielded enhanced anticancer responses and improved cancer survival. Nevertheless, the success rate of immunotherapy in cancer treatment has been below expectation(s) due to unpredictable efficacy and off-target effects from systemic dosing of immunotherapeutic. As a result, there is an unmet clinical need for improving conventional immunotherapy. Nanotechnology offers several new strategies, multimodality, and multiplex biological targeting advantage to overcome many of these challenges. These efforts enable programming the pharmacodynamics, pharmacokinetics, delivery of immunomodulatory agents/co-delivery of compounds to prime at the tumor sites for improved therapeutic benefits. This review provides an overview of the design …


Genome-Wide Association Study Of More Than 40,000 Bipolar Disorder Cases Provides New Insights Into The Underlying Biology, Niamh Mullins, Andreas J. Forstner, Kevin S. O’Connell, Brandon Coombes, Ney Alliey Rodriguez Jun 2021

Genome-Wide Association Study Of More Than 40,000 Bipolar Disorder Cases Provides New Insights Into The Underlying Biology, Niamh Mullins, Andreas J. Forstner, Kevin S. O’Connell, Brandon Coombes, Ney Alliey Rodriguez

School of Medicine Publications

Bipolar disorder is a heritable mental illness with complex etiology. We performed a genome-wide association study of 41,917 bipolar disorder cases and 371,549 controls of European ancestry, which identified 64 associated genomic loci. Bipolar disorder risk alleles were enriched in genes in synaptic signaling pathways and brain-expressed genes, particularly those with high specificity of expression in neurons of the prefrontal cortex and hippocampus. Significant signal enrichment was found in genes encoding targets of antipsychotics, calcium channel blockers, antiepileptics and anesthetics. Integrating expression quantitative trait locus data implicated 15 genes robustly linked to bipolar disorder via gene expression, encoding druggable targets …


Variant-Specific Inflation Factors For Assessing Population Stratification At The Phenotypic Variance Level, Tamar Sofer, Xiuwen Zheng, Cecelia A. Laurie, Stephanie M. Gogarten, Jennifer A. Brody, Matthew P. Conomos, Joshua C. Bis, Timothy A. Thornton, Adam Szpiro, Joanne E. Curran, Michael Mahaney Jun 2021

Variant-Specific Inflation Factors For Assessing Population Stratification At The Phenotypic Variance Level, Tamar Sofer, Xiuwen Zheng, Cecelia A. Laurie, Stephanie M. Gogarten, Jennifer A. Brody, Matthew P. Conomos, Joshua C. Bis, Timothy A. Thornton, Adam Szpiro, Joanne E. Curran, Michael Mahaney

School of Medicine Publications

In modern Whole Genome Sequencing (WGS) epidemiological studies, participant-level data from multiple studies are often pooled and results are obtained from a single analysis. We consider the impact of differential phenotype variances by study, which we term 'variance stratification'. Unaccounted for, variance stratification can lead to both decreased statistical power, and increased false positives rates, depending on how allele frequencies, sample sizes, and phenotypic variances vary across the studies that are pooled. We develop a procedure to compute variant-specific inflation factors, and show how it can be used for diagnosis of genetic association analyses on pooled individual level data from …


Air Pollution Exposure And Risk Of Adverse Obstetric And Neonatal Outcomes Among Women With Type 1 Diabetes, Andrew D. Williams, Jenna Kanner, Katherine Grantz, Marion Ouidir, Shanshan Sheehy, Seth Sherman, Candace Robledo, Pauline Mendola Jun 2021

Air Pollution Exposure And Risk Of Adverse Obstetric And Neonatal Outcomes Among Women With Type 1 Diabetes, Andrew D. Williams, Jenna Kanner, Katherine Grantz, Marion Ouidir, Shanshan Sheehy, Seth Sherman, Candace Robledo, Pauline Mendola

School of Medicine Publications

Aims/Hypothesis:

Women with type 1 diabetes have increased risk for poor obstetric outcomes. Prenatal air pollution exposure is also associated with adverse outcomes for women and infants. We examined whether women with type 1 diabetes are more vulnerable than other women to pollution-associated risks during pregnancy.

Methods:

In singleton deliveries from the Consortium on Safe Labor (2002-2008), obstetric and neonatal outcomes were compared for women with type 1 diabetes (n=507) and women without autoimmune disease (n=204,384). Preconception, trimester, and whole pregnancy average air pollutant exposure (ozone (O3), carbon monoxide (CO), particulate matter >10 microns (PM10), PM >2.5 microns (PM2.5), sulfur …


Effect Of Demographic And Health Dynamics On Cognitive Status In Mexico Between 2001 And 2015: Evidence From The Mexican Health And Aging Study, Silvia Mejia-Arango, Jaqueline Avila, Brian Downer, Marc A. Garcia, Alejandra Michaels-Obregon, Joseph L. Saenz, Rafael Samper-Ternent, Rebeca Wong Jun 2021

Effect Of Demographic And Health Dynamics On Cognitive Status In Mexico Between 2001 And 2015: Evidence From The Mexican Health And Aging Study, Silvia Mejia-Arango, Jaqueline Avila, Brian Downer, Marc A. Garcia, Alejandra Michaels-Obregon, Joseph L. Saenz, Rafael Samper-Ternent, Rebeca Wong

School of Medicine Publications

Sources of health disparities such as educational attainment, cardiovascular risk factors, and access to health care affect cognitive impairment among older adults. To examine the extent to which these counteracting changes affect cognitive aging over time among Mexican older adults, we examine how sociodemographic factors, cardiovascular diseases, and their treatment relate to changes in cognitive function of Mexican adults aged 60 and older between 2001 and 2015. Self and proxy respondents were classified as dementia, cognitive impairment no dementia (CIND), and normal cognition. We use logistic regression models to examine the trends in dementia and CIND for men and women …


Identifying The Lipidomic Effects Of A Rare Loss-Of-Function Deletion In Angptl3, Nicholas B. Blackburn, Peter J. Meikle, Juan M. Peralta, Satish Kumar, Ana C. Leandro, Melissa A. Bellinger, Michael Mahaney, Harald H. H. Goring, John L. Vandeberg, Sarah Williams-Blangero, David C. Glahn, Ravi Duggirala, John Blangero, Joanne E. Curran Jun 2021

Identifying The Lipidomic Effects Of A Rare Loss-Of-Function Deletion In Angptl3, Nicholas B. Blackburn, Peter J. Meikle, Juan M. Peralta, Satish Kumar, Ana C. Leandro, Melissa A. Bellinger, Michael Mahaney, Harald H. H. Goring, John L. Vandeberg, Sarah Williams-Blangero, David C. Glahn, Ravi Duggirala, John Blangero, Joanne E. Curran

School of Medicine Publications

Background: The identification and understanding of therapeutic targets for atherosclerotic cardiovascular disease is of fundamental importance given its global health and economic burden. Inhibition of ANGPTL3 (angiopoietin-like 3) has demonstrated a cardioprotective effect, showing promise for atherosclerotic cardiovascular disease treatment, and is currently the focus of ongoing clinical trials. Here, we assessed the genetic basis of variation in ANGPTL3 levels in the San Antonio Family Heart Study.

Methods: We assayed ANGPTL3 protein levels in ≈1000 Mexican Americans from extended pedigrees. By drawing upon existing plasma lipidome profiles and genomic data we conducted analyses to understand the genetic basis to variation …


Lactoferrin-Bearing Gold Nanocages For Gene Delivery In Prostate Cancer Cells In Vitro, Jamal Almowalad, Sukrut Somani, Partha Laskar, Jitkasem Meewan, Rothwelle J. Tate, Margaret Mullin, Christine Dufès May 2021

Lactoferrin-Bearing Gold Nanocages For Gene Delivery In Prostate Cancer Cells In Vitro, Jamal Almowalad, Sukrut Somani, Partha Laskar, Jitkasem Meewan, Rothwelle J. Tate, Margaret Mullin, Christine Dufès

School of Medicine Publications

Background: Gold nanocages have been widely used as multifunctional platforms for drug and gene delivery, as well as photothermal agents for cancer therapy. However, their potential as gene delivery systems for cancer treatment has been reported in combination with chemotherapeutics and photothermal therapy, but not in isolation so far. The purpose of this work was to investigate whether the conjugation of gold nanocages with the cancer targeting ligand lactoferrin, polyethylene glycol and polyethylenimine could lead to enhanced transfection efficiency on prostate cancer cells in vitro, without assistance of external stimulation.

Methods: Novel lactoferrin-bearing gold nanocages conjugated to polyethylenimine and …


End Of Life Decision-Making Challenges In A Latino Patient With Covid-19: Facing Barriers, Irma Huayanay, Celia Pantoja, Chelsea Chang May 2021

End Of Life Decision-Making Challenges In A Latino Patient With Covid-19: Facing Barriers, Irma Huayanay, Celia Pantoja, Chelsea Chang

School of Medicine Publications

COVID-19 pandemic brought difficult scenarios that patients and families are facing about end- of-life decisions. This exposed some weak areas in the healthcare system where we can continue improve in reducing disparities and emphasizing advance care planning from a primary level of care. We present a case of challenges in end-of-life decision-making in a Latino patient.