Medicine and Health Sciences Commons^™

The Epidemiology, Evaluation, And Assessment Of Lateral Ankle Sprains In Athletes, G. Javier Cavazos Jr., Lawrence B. Harkless

School of Medicine Publications

Approximately 30,000 ankle injuries occur every day in the United States. With the incidence estimated at more than 3 million a year and at a rate of 2.15/1,000 in the U.S. alone, medical specialists and other healthcare providers caring for the foot and ankle must take notice. Despite the millions of ankle injuries sustained annually, the true incidence may be underestimated, as fewer than half of individuals with ankle sprains seek medical attention from healthcare professionals. The economic burden associated with the evaluation, diagnosis, and treatment is close to $4 billion annually. Ankle sprains account for half of all sports …

Emerging Issues In Covid-19 Vaccination In Tropical Areas: Impact Of The Immune Response Against Helminths In Endemic Areas, Leonor Chacin-Bonilla, Nathalie Chacon, Alfonso J. Rodriguez-Morales

School of Medicine Publications

The Coronavirus Disease 2019 (COVID-19) pandemic has affected over 165 million people and caused the death of 3.4 million worldwide (up to May 20, 2021) (https://coronavirus.jhu.edu/map.html), becoming a serious problem of global public health and the worst epidemic in the last century, after the pandemic 1918 influenza. Researchers worldwide are trying to find valuable drugs against the Severe Acute Respiratory Syndrome coronavirus 2 (SARS-CoV-2). Some of them focused as antivirals, others targeted in other ways (e.g. immunomodulation) to relieve the symptoms of the infected patients and help lower the death toll throughout the world. Unfortunately, there is a lack of …

Arterial Dissection In Antiphospholipid Syndrome Patients: Two Case Reports And A Literature Review, Kadhim Al-Banaa, Alfarooq Alshaikhli, Asal Al-Hareeri, Mohammed Abdelhalim, Alsadiq Al-Hillan, Tejas Joshi

School of Medicine Publications

Antiphospholipid syndrome (APS) is a multisystemic autoimmune disease which presents with thromboembolic disease, pregnancy complications and the presence of antiphospholipid antibodies. There are some reports of arterial dissections in different sites of the body associated with APS. We describe two patients with APS who developed ischaemic stroke as a result of vertebral artery dissection in the absence of acquired and genetic risk factors for arterial dissection. We also conducted a systematic review of the literature for cases of arterial dissection associated with APS. We suspect that APS may be a potential cause of vasculopathy and arterial dissection. Further research is …

Clinical Implications Of Exosomes: Targeted Drug Delivery For Cancer Treatment, Andrew Massey, Shabnam Malik, Mohammed Sikander, Kyle Doxtater, Manish Tripathi, Sheema Khan, Murali M. Yallapu, Meena Jaggi, Subhash C. Chauhan, Bilal B. Hafeez

School of Medicine Publications

Exosomes are nanoscale vesicles generated by cells for intercellular communication. Due to their composition, significant research has been conducted to transform these particles into specific delivery systems for various disease states. In this review, we discuss the common isolation and loading methods of exosomes, some of the major roles of exosomes in the tumor microenvironment, as well as discuss recent applications of exosomes as drug delivery vessels and the resulting clinical implications

New Technology Add-On Payment (Ntap) For Viz Lvo: A Win For Stroke Care, Ameer E. Hassan

School of Medicine Publications

The Centers for Medicare and Medicaid Services (CMS) recently granted a New Technology Add-on Payment (NTAP) for Viz ContaCT (Viz LVO) by Viz.ai, Inc, an applied artificial intelligence healthcare company.1 This is the first time CMS has reimbursed an artificial intelligence (AI)-based software using this designation. It applies to Viz.ai’s acute ischemic stroke product, Viz LVO, officially known as Viz ContaCT, under which the ICD-10 Procedure Coding System (ICD-10-PCS) procedure code 4A03×5D was established. Viz ContaCT is an AI-based system that creates a parallel alert system whenever it detects a large vessel occlusion (LVO) on a computed tomography angiogram. …

Utilization Of The Ballast Long Guiding Sheath For Neuroendovascular Procedures: Institutional Experience In 68 Cases, Ameer E. Hassan, Elizabeth M. Burke, Marlon Monayao, Wondwossen G. Tekle

School of Medicine Publications

Background: The rise of neurointerventional devices has created a demand for guide systems capable of navigating to the carotid artery consistently regardless of tortuosity. The shift toward large distal access catheters (DACs) and desire for greater trackability have inspired the creation of flexible, supportive, large-lumen long guiding sheaths. Recently, the Ballast long guiding sheath was introduced to provide stability and flexibility while navigating neurointerventional devices through tortuous intracranial anatomy.

Objective: To report our experience using the Ballast long guiding sheath in a series of patients undergoing a variety of neuroendovascular procedures.

Methods: We retrospectively identified all patients who underwent neuroendovascular …

Intradural Extramedullary Primary Central Nervous System Melanoma Of The Craniovertebral Junction During Pregnancy: Observations And Outcomes, Fabiola Valenzuela, Sohum Desai

School of Medicine Publications

Background: Primary central nervous system (CNS) melanoma is a rare lesion derived from neural crest precursors. While its management is analogous to metastatic spinal melanoma, the literature does not describe this entity clearly in pregnant patients and the unique implications it presents. Here, we describe the case of a pregnant patient who presented with primary CNS melanoma of the cervical spine.

Case Description: A 27-year-old pregnant patient presented with a 3-month history of neck and interscapular pain. MRI of the cervical spine demonstrated a ventral intradural extramedullary mass adjacent to the C2-C3 vertebral bodies causing severe cord compression. The patient …

Two-Year Responses Of Heart Rate And Heart Rate Variability To First Occupational Lead Exposure, Yuling Yu, Lutgarde Thijs, Cai-Guo Yu, Wenyi Yang, Jesus D. Melgarejo, Dongmei Wei, Fangfei Wei, Tim S. Nawrot, Peter Verhamme, Harry Roels

School of Medicine Publications

Because of the falling lead exposure, the literature relating autonomous nervous function to blood lead (BL) has limited relevance. In the longitudinal Study for Promotion of Health in Recycling Lead (URL: https://www.clinicaltrials.gov; Unique identifier: NCT02243904), we recorded the 2-year responses of heart rate (HR), HR variability (HRV; Cardiax, International Medical Equipment Developing, Budapest, Hungary), and median nerve conduction velocity (Brevio, NeuMed, West Trenton, NJ), a routine test in occupational medicine, to first lead exposure in 195 newly hired workers (91.3% men; mean age, 27.8 years). High- and low-frequency HRV power and orthostatic HRV responses were derived from 5-minute ECGs …

Urinary Total Arsenic And Arsenic Methylation Capacity In Pregnancy And Gestational Diabetes Mellitus: A Case-Control Study, Wei-Jen Chen, Erin M. Davis, Julie A. Stoner, Candace A. Robledo, Jean R. Goodman, Tabitha Garwe, Amanda E. Janitz, Chao Xu, Jooyeon Hwang, Jennifer D. Peck

School of Medicine Publications

Previous studies suggest arsenic exposure may increase the risk of gestational diabetes mellitus (GDM). However, prior assessments of total arsenic concentrations have not distinguished between toxic and nontoxic species. Our study aimed to investigate the relationships between inorganic arsenic exposure, arsenic methylation capacity, and GDM.

Sixty-four cases of GDM and 237 controls were analyzed for urinary concentrations of inorganic arsenic species and their metabolites (arsenite (As3), arsenate (As5), monomethylarsonic acid (MMA), and dimethylarsinic acid (DMA)), and organic forms of arsenic. Inorganic arsenic exposure was defined as the sum of inorganic and methylated arsenic species (iSumAs). Methylation capacity indices were calculated …

Development And Validation Of A Predictive Model For Childhood Mortality After A Traumatic Brain Injury: Analysis Of The National Trauma Data Bank, Jooby Joy, Axel Moreira, Kevin Chorath, Karthik Rajasekaran, Alvaro Moreira

School of Medicine Publications

Introduction: Traumatic brain injury (TBI) is a significant cause of morbidity and mortality in children. While most TBI-related admissions are mild, identifying early predictors of poor outcome may assist clinicians with timely medical decisions and effective triage utilization.

Objective: We sought to develop and validate a clinical tool for predicting in-hospital death in children after a traumatic brain injury.

Methods: Data was collected for children (≤18 years) from the National Trauma Data Bank between the years of 2007 to 2015. We included children who sustained any TBI, defined as: (i) open and closed skull fractures, (ii) cerebellar, cortical, or brain …

Regulation Of Apoptosis During Environmental Skin Tumor Initiation, Bilal B. Hafeez, Eunmi Park, Kyung-Soo Chun, Yong-Yeon Cho, Dae Joon Kim

School of Medicine Publications

Skin cancer is more prevalent than any other cancer in the United States. Nonmelanoma skin cancers are the more common forms of skin cancer that affect individuals. The development of squamous cell carcinoma, the second most common type of skin cancer, can be stimulated by exposure of environmental carcinogens, such as chemical toxicants or UVB. It is developed by three distinct stages: initiation, promotion, and progression. During the initiation, the fate of DNA-damaged skin cells is determined by the homeostatic regulation of pro-apoptotic and antiapoptotic signaling pathways. The imbalance or disruption of either signaling will lead to the survival of …

Genetic And Non-Genetic Factors Affecting The Expression Of Covid-19-Relevant Genes In The Large Airway Epithelium, Silva Kasela, Victor E. Ortega, Molly Martorella, Suresh Garudadri, Jenna Nguyen, Elizabeth Ampleford, Anu Pasanen, Srilaxmi Nerella, John Blangero, Joanne E. Curran, Juan M. Peralta

School of Medicine Publications

Background: The large airway epithelial barrier provides one of the first lines of defense against respiratory viruses, including SARS-CoV-2 that causes COVID-19. Substantial inter-individual variability in individual disease courses is hypothesized to be partially mediated by the differential regulation of the genes that interact with the SARS-CoV-2 virus or are involved in the subsequent host response. Here, we comprehensively investigated non-genetic and genetic factors influencing COVID-19-relevant bronchial epithelial gene expression. Methods: We analyzed RNA-sequencing data from bronchial epithelial brushings obtained from uninfected individuals. We related ACE2 gene expression to host and environmental factors in the SPIROMICS cohort of smokers with …

Sacubitril/Valsartan Inhibits Obesity-Associated Diastolic Dysfunction Through Suppression Of Ventricular-Vascular Stiffness, Annayya R. Aroor, Srinivas Mummidi, Juan C. Lopez-Alvarenga, Nitin Das, Javad Habibi, Guanghong Jia, Guido Lastra, Bysani Chandrasekar

School of Medicine Publications

Objective: Cardiac diastolic dysfunction (DD) and arterial stiffness are early manifestations of obesity-associated prediabetes, and both serve as risk factors for the development of heart failure with preserved ejection fraction (HFpEF). Since the incidence of DD and arterial stiffness are increasing worldwide due to exponential growth in obesity, an effective treatment is urgently needed to blunt their development and progression. Here we investigated whether the combination of an inhibitor of neprilysin (sacubitril), a natriuretic peptide-degrading enzyme, and an angiotensin II type 1 receptor blocker (valsartan), suppresses DD and arterial stiffness in an animal model of prediabetes more effectively than valsartan …

Application Of An Evidence-Based, Out-Patient Treatment Strategy For Covid-19: Multidisciplinary Medical Practice Principles To Prevent Severe Disease☆, Elliot M. Frohman, Nicole R. Villemarette-Pittman, Adriana Rodriguez, Robert Glanzman, Sarah Rugheimer, Oleg Komogortsev, Scott S. Zamvil, Roberto A. Cruz, Thomas C. Varkey, Ashley N. Frohman

School of Medicine Publications

The COVID-19 pandemic has devastated individuals, families, and institutions throughout the world. Despite the breakneck speed of vaccine development, the human population remains at risk of further devastation. The decision to not become vaccinated, the protracted rollout of available vaccine, vaccine failure, mutational forms of the SARS virus, which may exhibit mounting resistance to our molecular strike at only one form of the viral family, and the rapid ability of the virus(es) to hitch a ride on our global transportation systems, means that we are will likely continue to confront an invisible, yet devastating foe. The enemy targets one of …

Propranolol For Treatment Of Infantile Hemangioma: Efficacy And Effect On Pediatric Growth And Development, Rachel A. Giese, Merit Turner, Mario Cleves, J. Reed Gardner, Gresham T. Richter

School of Medicine Publications

Purpose. Propranolol has been successful in treating problematic infantile hemangiomas (IH) but concerns regarding its effect on normal growth and development have been raised. This study examines physical growth, developmental milestones, and human growth hormone (hGH) levels in infants receiving propranolol for problematic IH.

Method. Monthly heights and weights of children undergoing propranolol therapy for IH were prospectively collected and tabulated. Data analysis and comparison to World Health Organization (WHO) weight-for-age and weight-to-length z-scores was performed. Questionnaires regarding milestones, efficacy, and guardian satisfaction were performed, and a combination of both chart results and phone conducted surveys was tabulated. Serum …

Regression Of Melanoma Following Intravenous Injection Of Plumbagin Entrapped In Transferrin-Conjugated, Lipid–Polymer Hybrid Nanoparticles, Intouch Sakpakdeejaroen, Sukrut Somani, Partha Laskar, Margaret Mullin, Christine Dufès

School of Medicine Publications

Background: Plumbagin, a naphthoquinone extracted from the officinal leadwort presenting promising anti-cancer properties, has its therapeutic potential limited by its inability to reach tumors in a specific way at a therapeutic concentration following systemic injection. The purpose of this study is to assess whether a novel tumor-targeted, lipid–polymer hybrid nanoparticle formulation of plumbagin would suppress the growth of B16-F10 melanoma in vitro and in vivo.

Methods: Novel lipid–polymer hybrid nanoparticles entrapping plumbagin and conjugated with transferrin, whose receptors are present in abundance on many cancer cells, have been developed. Their cellular uptake, anti-proliferative and apoptosis efficacy were assessed on various …

Plga Nanoparticle-Based Formulations To Cross The Blood–Brain Barrier For Drug Delivery: From R&D To Cgmp, Kaining Zhi, Babatunde Raji, Anantha R. Nookala, Mohammad Moshahid Khan, Xuyen H. Nguyen, Swarna Sakshi, Tayebeh Pourmotabbed, Murali M. Yallapu

School of Medicine Publications

The blood–brain barrier (BBB) is a natural obstacle for drug delivery into the human brain, hindering treatment of central nervous system (CNS) disorders such as acute ischemic stroke, brain tumors, and human immunodeficiency virus (HIV)-1-associated neurocognitive disorders. Poly(lactic-co-glycolic acid) (PLGA) is a biocompatible polymer that is used in Food and Drug Administration (FDA)-approved pharmaceutical products and medical devices. PLGA nanoparticles (NPs) have been reported to improve drug penetration across the BBB both in vitro and in vivo. Poly(ethylene glycol) (PEG), poly(vinyl alcohol) (PVA), and poloxamer (Pluronic) are widely used as excipients to further improve the stability and effectiveness of PLGA …

Using The Schmahmann Syndrome Scale To Assess Cognitive Impairment In Young Adults With Metabolic Syndrome: A Hypothesis-Generating Report, Eithan Kotkowski, Larry R. Price, Cheasequah J. Blevins, Crystal Franklin, Mary Woolsey, Ralph A. Defronzo, John Blangero, Ravindranath Duggirala, David C. Glahn, Jeremy Schmahmann, Peter T. Fox

School of Medicine Publications

The posterior cerebellum is the most significantly compromised brain structure in individuals with metabolic syndrome (MetS) (Kotkowski et al., 2019). In light of this, we hypothesized that cognitive decline reported in patients with MetS is likely related to posterior cerebellar atrophy. In this study, we performed a post-hoc analyses using T1-weighted magnetic resonance imaging (MRI), diffusion tensor imaging (DTI) in the form of voxel-wise tract-based spatial statistics (TBSS), biometric, and psychometric data from young participants with (n = 52, aged 18–35 years) and without MetS (n = 52, aged 18–35 years). To test the predictive value of components …

Serotonergic Therapy In Epilepsy, Frank Gilliam, Hrvoje Hećimović, Matthew S. Gentry

School of Medicine Publications

Purpose of review

The serotonergic system is implicated in multiple aspects of epilepsy, including seizure susceptibility, sudden unexpected death in epilepsy (SUDEP), and comorbid depression. Despite the complexity of serotonin’s effects on various neuronal networks, ongoing research provides considerable insight into the role of serotonin in human epilepsy. This review explores the potential roles of serotonergic therapies to improve clinical outcomes in epilepsy.

Recent findings

In recent decades research has markedly increased our knowledge of the diverse effects of serotonin on brain function. Animal models of epilepsy have identified the influence of serotonin on seizure threshold in specific brain regions, …

Bipolar Multiplex Families Have An Increased Burden Of Common Risk Variants For Psychiatric Disorders, Till F.M. Andlauer, Jose Guzman-Parra, Fabian Streit, Jana Strohmaier, Ney Alliey Rodriguez

School of Medicine Publications

Multiplex families with a high prevalence of a psychiatric disorder are often examined to identify rare genetic variants with large effect sizes. In the present study, we analysed whether the risk for bipolar disorder (BD) in BD multiplex families is influenced by common genetic variants. Furthermore, we investigated whether this risk is conferred mainly by BD-specific risk variants or by variants also associated with the susceptibility to schizophrenia or major depression. In total, 395 individuals from 33 Andalusian BD multiplex families (166 BD, 78 major depressive disorder, 151 unaffected) as well as 438 subjects from an independent, BD case/control cohort …

Genetic Influences On Externalizing Psychopathology Overlap With Cognitive Functioning And Show Developmental Variation, Josephine Mollon, Emma E. M. Knowles, Samuel R. Mathias, Amanda Rodrigue, Tyler M. Moore, Monica E. Calkins, Ruben C. Gur, Juan M. Peralta, Daniel J. Weiner, John Blangero, Laura Almasy

School of Medicine Publications

Background: Questions remain regarding whether genetic influences on early life psychopathology overlap with cognition and show developmental variation.

Methods: Using data from 9,421 individuals aged 8-21 from the Philadelphia Neurodevelopmental Cohort, factors of psychopathology were generated using a bifactor model of item-level data from a psychiatric interview. Five orthogonal factors were generated: anxious-misery (mood and anxiety), externalizing (attention deficit hyperactivity and conduct disorder), fear (phobias), psychosis-spectrum, and a general factor. Genetic analyses were conducted on a subsample of 4,662 individuals of European American ancestry. A genetic relatedness matrix was used to estimate heritability of these factors, and genetic correlations with …

High Variation In Immune Responses And Parasite Phenotypes In Naturally Acquired Trypanosoma Cruzi Infection In A Captive Nonhuman Primate Breeding Colony In Texas, Usa, Angel M. Padilla, Phil Y. Yao, Tre J. Landry, Gretchen M. Cooley, Susan M. Mahaney, Isabela Ribeiro, John L. Vandeberg, Rick L. Tarleton

School of Medicine Publications

Trypanosoma cruzi, the causative agent of human Chagas disease, is endemic to the southern region of the United States where it routinely infects many host species. The indoor/outdoor housing configuration used in many non-human primate research and breeding facilities in the southern of the USA provides the opportunity for infection by T. cruzi and thus provides source material for in-depth investigation of host and parasite dynamics in a natural host species under highly controlled and restricted conditions. For cynomolgus macaques housed at such a facility, we used a combination of serial blood quantitative PCR (qPCR) and hemoculture to confirm infection …

Perspectives On Self-Managed Abortion Among Providers In Hospitals Along The Texas– Mexico Border, Sarah Raifman, Sarah E. Baum, Kari White, Kristine Hopkins, Tony Ogburn, Daniel Grossman

School of Medicine Publications

Background

Following self-managed abortion (SMA), or a pregnancy termination attempt outside of the formal health system, some patients may seek care in an emergency department. Information about provider experiences treating these patients in hospital settings on the Texas-Mexico border is lacking.

Methods

The study team conducted semi-structured interviews with physicians, advanced practice clinicians, and nurses who had experience with patients presenting with early pregnancy complications in emergency and/or labor and delivery departments in five hospitals near the Texas-Mexico border. Interview questions focused on respondents’ roles at the hospital, knowledge of abortion services and laws, perspectives on SMA trends, experiences treating …

Disease Modeling And Disease Gene Discovery In Cardiomyopathies: A Molecular Study Of Induced Pluripotent Stem Cell Generated Cardiomyocytes, Satish Kumar, Joanne E. Curran, Kashish Kumar, Erica De Leon, Ana C. Leandro, Juan M. Peralta, Sarah Williams-Blangero, John Blangero

School of Medicine Publications

The in vitro modeling of cardiac development and cardiomyopathies in human induced pluripotent stem cell (iPSC)-derived cardiomyocytes (CMs) provides opportunities to aid the discovery of genetic, molecular, and developmental changes that are causal to, or influence, cardiomyopathies and related diseases. To better understand the functional and disease modeling potential of iPSC-differentiated CMs and to provide a proof of principle for large, epidemiological-scale disease gene discovery approaches into cardiomyopathies, well-characterized CMs, generated from validated iPSCs of 12 individuals who belong to four sibships, and one of whom reported a major adverse cardiac event (MACE), were analyzed by genome-wide mRNA sequencing. The …

1q21.1 Distal Copy Number Variants Are Associated With Cerebral And Cognitive Alterations In Humans, Ida E. Sønderby, Dennis Van Der Meer, Clara Moreau, Tobias Kaufmann, G. Bragi Walters, Maria Ellegaard, Nicholas B. Blackburn, John Blangero, Joanne E. Curran, Juan M. Peralta

School of Medicine Publications

Low-frequency 1q21.1 distal deletion and duplication copy number variant (CNV) carriers are predisposed to multiple neurodevelopmental disorders, including schizophrenia, autism and intellectual disability. Human carriers display a high prevalence of micro- and macrocephaly in deletion and duplication carriers, respectively. The underlying brain structural diversity remains largely unknown. We systematically called CNVs in 38 cohorts from the large-scale ENIGMACNV collaboration and the UK Biobank and identified 28 1q21.1 distal deletion and 22 duplication carriers and 37,088 non-carriers (48% male) derived from 15 distinct magnetic resonance imaging scanner sites. With standardized methods, we compared subcortical and cortical brain measures (all) and cognitive …

Genome-Wide Association Studies Of Schizophrenia And Bipolar Disorder In A Diverse Cohort Of Us Veterans, Tim B. Bigdeli, Ayman H. Fanous, Yuli Li, Nallakkandi Rajeevan, Frederick Sayward, Giulio Genovese, Rishab Gupta, Krishnan Radhakrishnan, Anil K. Malhotra, Michael A. Escamilla

School of Medicine Publications

Background: Schizophrenia (SCZ) and bipolar disorder (BIP) are debilitating neuropsychiatric disorders, collectively affecting 2% of the world's population. Recognizing the major impact of these psychiatric disorders on the psychosocial function of more than 200 000 US Veterans, the Department of Veterans Affairs (VA) recently completed genotyping of more than 8000 veterans with SCZ and BIP in the Cooperative Studies Program (CSP) #572.

Methods: We performed genome-wide association studies (GWAS) in CSP #572 and benchmarked the predictive value of polygenic risk scores (PRS) constructed from published findings. We combined our results with available summary statistics from several recent GWAS, realizing the …

Shared And Anxiety-Specific Pediatric Psychopathology Dimensions Manifest Distributed Neural Correlates, Julia O. Linke, Rany Abend, Katharina Kircanski, Michal Clayton, Caitlin Stavish, Brenda E. Benson, Melissa A. Brotman, Olivier Renaud, Stephen M. Smith, Anderson M. Winkler

School of Medicine Publications

Background:

Imaging research has not yet delivered reliable psychiatric biomarkers. One challenge, particularly among youth, is high comorbidity. This challenge might be met through canonical correlation analysis (CCA) designed to model mutual dependencies between symptom dimensions and neural measures. We map the multivariate associations that intrinsic functional connectivity manifests with pediatric symptoms of anxiety, irritability, and attention-deficit/hyperactivity disorder (ADHD) as common, impactful, co-occurring problems. We evaluate the replicability of such latent dimensions in an independent sample.

Methods:

We obtained ratings of anxiety, irritability, and ADHD, and 10 minutes of resting-state functional magnetic resonance imaging data, from two independent cohorts. Both …

Robust, Flexible, And Scalable Tests For Hardy-Weinberg Equilibrium Across Diverse Ancestries, Alan M. Kwong, Thomas W. Blackwell, Jonathon Lefaive, Mariza De Andrade, John Barnard, Kathleen C. Barnes, John Blangero

School of Medicine Publications

Traditional Hardy-Weinberg equilibrium (HWE) tests (the χ2 test and the exact test) have long been used as a metric for evaluating genotype quality, as technical artifacts leading to incorrect genotype calls often can be identified as deviations from HWE. However, in datasets comprised of individuals from diverse ancestries, HWE can be violated even without genotyping error, complicating the use of HWE testing to assess genotype data quality. In this manuscript, we present the Robust Unified Test for HWE (RUTH) to test for HWE while accounting for population structure and genotype uncertainty, and evaluate the impact of population heterogeneity and genotype …

Bioactive Nanotherapeutic Trends To Combat Triple Negative Breast Cancer, Pallabita Chowdhury, Upasana Ghosh, Kamalika Samanta, Meena Jaggi, Subhash C. Chauhan, Murali M. Yallapu

School of Medicine Publications

The management of aggressive breast cancer, particularly, triple negative breast cancer (TNBC) remains a formidable challenge, despite treatment advancement. Although newer therapies such as atezolizumab, olaparib, and sacituzumab can tackle the breast cancer prognosis and/or progression, but achieved limited survival benefit(s). The current research efforts are aimed to develop and implement strategies for improved bioavailability, targetability, reduce systemic toxicity, and enhance therapeutic outcome of FDA-approved treatment regimen. This review presents various nanoparticle technology mediated delivery of chemotherapeutic agent(s) for breast cancer treatment. This article also documents novel strategies to employ cellular and cell membrane cloaked (biomimetic) nanoparticles for effective clinical …

Research On Aging During The Venezuelan Humanitarian Crisis: The Experience Of The Maracaibo Aging Study, Gladys E. Maestre, Rosa V. Pirela, Carmen Paz, Jesus D. Melgarejo, Luis J. Mena, Carlos A. Chavez, Reinier Leendertz, Michele Petitto, Egle Silva, Gustavo E. Calmon

School of Medicine Publications

Background

Venezuela is in the throes of a complex humanitarian crisis that is one of the worst in decades to impact any country outside of wartime. This case analysis describes the challenges faced by the ongoing Maracaibo Aging Study (MAS) during the deteriorating conditions in Venezuela. When the MAS began in 1997, it focused on memory-related disorders. Since then, strategic planning and proactive community participation allowed us to anticipate and address logistical, funding, and ethical challenges, and facilitated the enrollment and retention of more than 2500 subjects over 55 years of age. All participants, who are residents of the city …