Medicine and Health Sciences Commons^™

Tannic Acid Inhibits Lipid Metabolism And Induce Ros In Prostate Cancer Cells, Prashanth K.B. Nagesh, Elham Hatami, Pallabita Chowdhury, Shashi Jaun, Nirnoy Dan, Vivek Kumar Kashyap, Subhash C. Chauhan, Meena Jaggi, Murali M. Yallapu

School of Medicine Publications

Prostate cancer (PCa) cells exploit the aberrant lipid signaling and metabolism as their survival advantage. Also, intracellular storage lipids act as fuel for the PCa proliferation. However, few studies were available that addressed the topic of targeting lipid metabolism in PCa. Here, we assessed the tannic acid (TA) lipid-targeting ability and its capability to induce endoplasmic reticulum (ER) stress by reactive oxygen species (ROS) in PCa cells. TA exhibited dual effects by inhibiting lipogenic signaling and suppression of lipid metabolic pathways. The expression of proteins responsible for lipogenesis was down regulated. The membrane permeability and functionality of PCa were severely …

Fbxw7-Mediated Stability Regulation Of Signal Transducer And Activator Of Transcription 2 In Melanoma Formation, Cheol-Jung Lee, Hyun-Jung An, Seung-Min Kim, Sun-Mi Yoo, Juhee Park, Ga-Eun Lee, Woo-Young Kim, Dae Joon Kim, Han Chang Kang, Joo Young Lee

School of Medicine Publications

In this study, we provide critical evidence that STAT2 stability regulation plays an essential role in melanoma cell proliferation and colony growth. We found that the interaction of FBXW7 and STAT2 induced STAT2 destabilization via a ubiquitination-mediated proteasomal degradation pathway. Notably, GSK3β-mediated STAT2 phosphorylation facilitated STAT2–FBXW7 interactions via the DNA binding domain of STAT2 and domains 1, 2, 6, and 7 of FBXW7 WD40. Importantly, the inverse correlation between protein levels of STAT2 and FBXW7 were observed not only in human melanoma cells but also in a human skin cancer tissue array. The relationship between protein levels of STAT2 and …

Hypothetical Human Immune Genome Complex Gradient May Help To Explain The Congenital Zika Symdrome Catastrophe In Brazil: A New Theory, F. R. S. Oliveira, C. C. Bresani-Salvi, C. N. L. Morais, A. W. Bigham, U. Braga-Neto, Gladys E. Maestre, John L. Vandeberg, E. T. A. Marques, B. Acioli-Santos

School of Medicine Publications

There are few data considering human genetics as an important risk factor for birth abnormalities related to ZIKV infection during pregnancy, even though sub-Saharan African populations are apparently more resistant to CZS as compared to populations in the Americas. We hypothesized that single nucleotide variants (SNVs), especially in innate immune genes, could make some populations more susceptible to Zika congenital complications than others. Differences in the SNV frequencies among continental populations provide great potential for Machine Learning techniques. We explored a key immune genomic gradient between individuals from Africa, Asia and Latin America, working with complex signatures, using 297 SNVs. …

One-Year Changes In Brain Microstructure Differentiate Preclinical Huntington's Disease Stages, Chris Patrick Pflanz, Marina Charquero-Ballester, D S. Majid, Anderson M. Winkler, Emmanuel Vallée, Adam R. Aron, Mark Jenkinson, Gwenaëlle Douaud

School of Medicine Publications

OBJECTIVE: To determine whether brain imaging markers of tissue microstructure can detect the effect of disease progression across the preclinical stages of Huntington's disease.

METHODS: Longitudinal microstructural changes in diffusion imaging metrics (mean diffusivity and fractional anisotropy) were investigated in participants with presymptomatic Huntington's disease (N = 35) stratified into three preclinical subgroups according to their estimated time until onset of symptoms, compared with age- and gender-matched healthy controls (N = 19) over a 1y period.

RESULTS: Significant differences were found over the four groups in change of mean diffusivity in the posterior basal ganglia and the splenium of the …

Tgif1-Twist1 Axis In Pancreatic Ductal Adenocarcinoma, Mohammed S. Razzaque, Azeddine Atfi

School of Medicine Publications

TG-interacting factor 1 (TGIF1) exerts inhibitory effects on transforming growth factor-beta (TGF-β) signaling by suppressing Smad signaling pathway at multiple levels. TGIF1 activity is important for normal embryogenesis and organogenesis, yet its dysregulation can culminate in tumorigenesis. For instance, increased expression of TGIF1 correlates with poor prognosis in triple-negative breast cancer patients, and enforced expression of TGIF1 facilitates Wnt-driven mammary tumorigenesis, suggesting that TGIF1 might function as an oncoprotein. Quite surprisingly, TGIF1 has recently been shown to function as a tumor suppressor in pancreatic ductal adenocarcinoma (PDAC), possibly owing to its ability to antagonize the pro-malignant transcription factor …

Recent Advances On Visual Cycle Protein Research And Progress On Clinical Translation, Xin Yee Ooi, Rujman Khan, Anjalee Choudhury, Francisco Xavier Elisarraras, Jeff Grigsby, Brandi Obregon, Andrew T C Tsin

School of Medicine Publications

Since the publication of our previous paper, Visual cycle proteins: Structure, function, and roles in human retinal disease (Tsin, et.al, JBC 293:13016, 2018) there has been significant progress on multiple topics discussed in this paper. In the present communication, we further explore research advances on two visual cycle proteins: DES1 and IRBP. In addition, we emphasize the progress of clinical translation of other visual cycle protein research, including the breakthrough of FDA-approved gene therapy for Leber’s congenital amaurosis, and additional gene therapies at different stages of clinical trials for various retinal diseases such as retinitis pigmentosa, diabetic retinopathy, and Stargardt’s …

Intrauterine Exposure To Chronic Hypoxia In The Rat Leads To Progressive Diastolic Function And Increased Aortic Stiffness From Early Postnatal Developmental Stages, Praveen Kumar, Jude S. Morton, Amin Shah, Victor Do, Consolato Sergi, Jesus Serrano-Lomelin, Sandra T. Davidge, Donna Beker, Jody Levasseur, Lisa K. Hornberger

School of Medicine Publications

Aim

We sought to explore whether fetal hypoxia exposure, an insult of placental insufficiency, is associated with left ventricular dysfunction and increased aortic stiffness at early postnatal ages.

Methods

Pregnant Sprague Dawley rats were exposed to hypoxic conditions (11.5% FiO2) from embryonic day E15‐21 or normoxic conditions (controls). After delivery, left ventricular function and aortic pulse wave velocity (measure of aortic stiffness) were assessed longitudinally by echocardiography from day 1 through week 8. A mixed ANOVA with repeated measures was performed to compare findings between groups across time. Myocardial hematoxylin and eosin and picro‐sirius staining were performed to evaluate myocyte …

Uncovering The Complex Genetics Of Human Personality: Response From Authors On The Pgmra Model, Igor Zwir, Pashupati Mishra, Coral Del-Val, C. Charles Gu, Gabriel A. De Erausquin, Terho Lehtimäki, C. Robert Cloninger

School of Medicine Publications

Following publication of our two articles [1, 2], a critique of the methodology of Phenotype-Genotype Many-to-Many Relations Analysis (PGMRA) [1, 3, 4] questioned the validity of our results from the perspective of polygenic risk scores (PRS) [5]. We appreciate the importance of these questions, and here provide a concise discussion of the assumptions and mathematical constraints of both approaches. We thank this commentator and others who have discussed our articles with us for their thoughtful questions and critiques

Ssa Positivity As Predictor Of Relapse In Patients With Neuromyelitis Optica Spectrum Disorder, Roberto A. Cruz, Alexander B. Ramos, Bridget A. Bagert, Jesus F. Lovera

School of Medicine Publications

No abstract provided.

Diet-Induced Leukocyte Telomere Shortening In A Baboon Model For Early Stage Atherosclerosis, Genesio M. Karere, Michael C. Mahaney, Deborah E. Newman, Angelica M. Riojas, Clint Christensen, Shifra Birnbaum, John L. Vandeberg, Laura Cox

School of Medicine Publications

Reported associations between leukocyte telomere length (LTL) attrition, diet and cardiovascular disease (CVD) are inconsistent. This study explores effects of prolonged exposure to a high cholesterol high fat (HCHF) diet on LTL in a baboon model of atherosclerosis. We measured LTL by qPCR in pedigreed baboons fed a chow (n = 105) or HCHF (n = 106) diet for 2 years, tested for effects of diet on LTL, and association between CVD risk factors and atherosclerotic lesions with LTL. Though not different at baseline, after 2 years median LTL is shorter in HCHF fed baboons (P < 0.0001). Diet predicts sex- and age-adjusted LTL and LTL attrition (P = 0.0009 and 0.0156, respectively). Serum concentrations of CVD biomarkers are associated with LTL at the 2-year endpoint and LTL accounts approximately 6% of the variance in aortic lesions (P = 0.04). Although heritable at baseline (h2 = 0.27, P = 0.027) and after 2 years (h2 = 0.46, P = 0.0038), baseline LTL does not predict lesion extent after 2 years. Atherogenic diet influences LTL, and LTL is a potential biomarker for early atherosclerosis. Prolonged exposure to an atherogenic diet decreases LTL and increases LTL attrition, and shortened LTL is associated with early-stage atherosclerosis in pedigreed baboons.

Veru-111 Suppresses Tumor Growth And Metastatic Phenotypes Of Cervical Cancer Cells Through The Activation Of P53 Signaling Pathway, Vivek Kumar Kashyap, Nirnoy Dan, Neeraj Chauhan, Qinghai Wang, Saini Setua, Prashanth K. B. Nagesh, Shabnam Malik, Vivek Batra, Murali M. Yallapu, Duane D. Miller, Bilal B. Hafeez, Meena Jaggi, Subhash C. Chauhan

School of Medicine Publications

In this study, we investigated the therapeutic efficacy of VERU-111 in vitro and in vivo model systems of cervical cancer. VERU-111 treatment inhibited cell proliferation and, clonogenic potential, induce accumulation of p53 and down regulated the expression of HPV E6/E7 expression in cervical cancer cells. In addition, VERU-111 treatment also decreased the expression of phosphorylation of Jak2 (TyR1007/1008) and STAT3 at Tyr705 and Ser727. VERU-111 treatment arrested cell cycle in the G2/M phase and modulated cell cycle regulatory proteins (cyclin B1, p21 p34cdc2 and pcdk1). Moreover, VERU-111 treatment induced apoptosis and modulated the expression of Bid, Bcl-xl, Survivin, Bax, Bcl2 …

Use Of >100,000 Nhlbi Trans-Omics For Precision Medicine (Topmed) Consortium Whole Genome Sequences Improves Imputation Quality And Detection Of Rare Variant Associations In Admixed African And Hispanic/Latino Populations, Madeline H. Kowalski, Huijun Qian, Ziyi Hou, Jonathan D. Rosen, Amanda L. Tapia, Yue Shan, Deepti Jain, Maria Argos, John Blangero, Juan M. Peralta

School of Medicine Publications

Most genome-wide association and fine-mapping studies to date have been conducted in individuals of European descent, and genetic studies of populations of Hispanic/Latino and African ancestry are limited. In addition, these populations have more complex linkage disequilibrium structure. In order to better define the genetic architecture of these understudied populations, we leveraged >100,000 phased sequences available from deep-coverage whole genome sequencing through the multi-ethnic NHLBI Trans-Omics for Precision Medicine (TOPMed) program to impute genotypes into admixed African and Hispanic/Latino samples with genome-wide genotyping array data. We demonstrated that using TOPMed sequencing data as the imputation reference panel improves genotype imputation …

Genome-Wide Meta-Analysis Of Macronutrient Intake Of 91,114 European Ancestry Participants From The Cohorts For Heart And Aging Research In Genomic Epidemiology Consortium, Jordi Merino, Hassan S. Dashti, Sherly X. Li, Chloé Sarnowski, Anne E. Justice, Misa Graff, Constantina Papoutsakis, Caren E. Smith, George V. Dedoussis, John Blangero

School of Medicine Publications

Macronutrient intake, the proportion of calories consumed from carbohydrate, fat, and protein, is an important risk factor for metabolic diseases with significant familial aggregation. Previous studies have identified two genetic loci for macronutrient intake, but incomplete coverage of genetic variation and modest sample sizes have hindered the discovery of additional loci. Here, we expanded the genetic landscape of macronutrient intake, identifying 12 suggestively significant loci (P < 1 × 10-6) associated with intake of any macronutrient in 91,114 European ancestry participants. Four loci replicated and reached genome-wide significance in a combined meta-analysis including 123,659 European descent participants, unraveling two novel loci; a common variant in RARB locus for carbohydrate intake and a rare variant in DRAM1 locus for protein intake, and corroborating earlier FGF21 and FTO findings. In additional analysis of 144,770 participants from the UK Biobank, all identified associations from the two-stage analysis were confirmed except for DRAM1. Identified loci might have implications in brain and adipose tissue biology and have clinical impact in obesity-related phenotypes. Our findings provide new insight into biological functions related to macronutrient intake.

Reck Suppresses Interleukin-17/Traf3ip2-Mediated Mmp-13 Activation And Human Aortic Smooth Muscle Cell Migration And Proliferation, Srinivas Mummidi, Nitin A. Das, Andrea J. Carpenter, Tadashi Yoshida, Manjunath Yariswamy, Ricardo Mostany, Reza Izadpanah, Yusuke Higashi, Sergiy Sukhanov, Makoto Noda, Ulrich Siebenlist, Randy S. Rector, Bysani Chandrasekar

School of Medicine Publications

Sustained inflammation and matrix metalloproteinase (MMP) activation contribute to vascular occlusive/proliferative disorders. Interleukin-17 (IL-17) is a proinflammatory cytokine that signals mainly via TRAF3 Interacting Protein 2 (TRAF3IP2), an upstream regulator of various critical transcription factors, including AP-1 and NF-κB. Reversion inducing cysteine rich protein with kazal motifs (RECK) is a membrane-anchored MMP inhibitor. Here we investigated whether IL-17A/TRAF3IP2 signaling promotes MMP-13-dependent human aortic smooth muscle cell (SMC) proliferation and migration, and determined whether RECK overexpression blunts these responses. Indeed, IL-17A treatment induced (a) JNK, p38 MAPK, AP-1, NF-κB, and CREB activation, (b) miR-21 induction, (c) miR-27b and miR-320 inhibition, (d) …

Nrxn1 Is Associated With Enlargement Of The Temporal Horns Of The Lateral Ventricles In Psychosis, Ney Alliey-Rodriguez, Tamar A. Grey, Rebecca Shafee, Huma Asif, Ney Alliey Rodriguez

School of Medicine Publications

Schizophrenia, Schizoaffective, and Bipolar disorders share behavioral and phenomenological traits, intermediate phenotypes, and some associated genetic loci with pleiotropic effects. Volumetric abnormalities in brain structures are among the intermediate phenotypes consistently reported associated with these disorders. In order to examine the genetic underpinnings of these structural brain modifications, we performed genome-wide association analyses (GWAS) on 60 quantitative structural brain MRI phenotypes in a sample of 777 subjects (483 cases and 294 controls pooled together). Genotyping was performed with the Illumina PsychChip microarray, followed by imputation to the 1000 genomes multiethnic reference panel. Enlargement of the Temporal Horns of Lateral Ventricles …

Opposing Age-Related Trends In Absolute And Relative Risk Of Adverse Health Outcomes Associated With Out-Of-Office Blood Pressure, Yan Li, Lutgarde Thijs, Zhen-Yu Zhang, Kei Asayama, Tine W. Hansen, José Boggia, Kristina Björklund-Bodegård, Wen-Yi Yang, Gladys E. Maestre

School of Medicine Publications

Participant-level meta-analyses assessed the age-specific relevance of office blood pressure to cardiovascular complications, but this information is lacking for out-of-office blood pressure. At baseline, daytime ambulatory (n=12 624) or home (n=5297) blood pressure were measured in 17 921 participants (51.3% women; mean age, 54.2 years) from 17 population cohorts. Subsequently, mortality and cardiovascular events were recorded. Using multivariable Cox regression, floating absolute risk was computed across 4 age bands (≤60, 61-70, 71-80, and >80 years). Over 236 491 person-years, 3855 people died and 2942 cardiovascular events occurred. From levels as low as 110/65 mm Hg, risk log-linearly increased with higher …

Dexamethasone As Abortive Treatment For Refractory Seizures Or Status Epilepticus In The Inpatient Setting, Alexander B. Ramos, Roberto A. Cruz, Nicole R. Villemarette-Pittman, Piotr W. Olejniczak, Edward C. Mader Jr.

School of Medicine Publications

Refractory seizures or status epilepticus (RS/SE) continues to be a challenge in the inpatient setting. Failure to abort a seizure with antiepileptic drugs (AEDs) may lead to intubation and treatment with general anesthesia exposing patients to complications, extending hospitalization, and increasing the cost of care. Studies have shown a key role of inflammatory mediators in seizure generation and termination. We describe 4 patients with RS/SE that was aborted when dexamethasone was added to conventional AEDs: a 61-year-old female with temporal lobe epilepsy who presented with delirium, nonconvulsive status epilepticus, and oculomyoclonic status; a 56-year-old female with history of traumatic left …

Full Recovery From Cocaine-Induced Toxic Leukoencephalopathy: Emphasizing The Role Of Neuroinflammation And Brain Edema, Edward C. Mader Jr., Alexander B. Ramos, Roberto A. Cruz, Lionel A. Branch

School of Medicine Publications

Toxic leukoencephalopathy (TL) is characterized by white matter disease on magnetic resonance imaging (MRI) and evidence of exposure to a neurotoxic agent. We describe a case of cocaine-induced TL in which extensive white matter disease did not preclude full recovery. A 57-year-old man with substance abuse disorder presented with a 5-day history of strange behavior. On admission, he was alert but had difficulty concentrating, psychomotor retardation, and diffuse hyperreflexia. Brain MRI revealed confluent subcortical white matter hyperintensities with restricted diffusion in some but not in other areas. Electroencephalography (EEG) showed mild diffuse slowing. Blood tests were normal except for mild …

Crossover Interference And Sex-Specific Genetic Maps Shape Identical By Descent Sharing In Close Relatives, Madison Caballero, Daniel N. Seidman, Ying Qiao, Jens Sannerud, Thomas D. Dyer, Donna M. Lehman, Joanne E. Curran, Ravindranath Duggirala, John Blangero, Shai Carmi, Amy L. Williams

School of Medicine Publications

Simulations of close relatives and identical by descent (IBD) segments are common in genetic studies, yet most past efforts have utilized sex averaged genetic maps and ignored crossover interference, thus omitting features known to affect the breakpoints of IBD segments. We developed Ped-sim, a method for simulating relatives that can utilize either sex-specific or sex averaged genetic maps and also either a model of crossover interference or the traditional Poisson model for inter-crossover distances. To characterize the impact of previously ignored mechanisms, we simulated data for all four combinations of these factors. We found that modeling crossover interference decreases the …

Mind, Brain, And Behavior: An Integrative Approach To Teaching Neuroscience To Medical Students, Arden D. Dingle, Annelyn Torres-Reveron, Mario Gil, Francisco Fernandez, Ignacio Martinez Escobedo, Valerie Terry, Gladys E. Maestre, Gabriel A. De Erausquin

School of Medicine Publications

Disorders related to neuroscience, psychiatry, and neurology cause significant disease burdens impacting medical practice [1, 2]. Teaching medical students these subjects remains challenging as many consider neuroscience and neurology too difficult to adequately learn [3] and psychiatry to be irrelevant [4–7]. Developing and implementing curricular initiatives to effectively teach these subjects so that students can utilize these knowledge and skills in practice is essential.

Interactive educational methods offer new approaches to improve student learning, especially within current educational initiatives that emphasize integration of basic and clinical science and incorporation of social …

Optical Detection Of The Structural Properties Of Tumor Tissue Generated By Xenografting Of Drug-Sensitive And Drug-Resistant Cancer Cells Using Partial Wave Spectroscopy (Pws), Prakash A. Adhikari, Prashanth K.B. Nagesh, Fatemah Alharthi, Subhash C. Chauhan, Meena Jaggi, Murali M. Yallapu, Prabhakar Pradhan

School of Medicine Publications

A mesoscopic physics-based optical imaging technique, partial wave spectroscopy (PWS), has been used for the detection of cancer by probing nanoscale structural alterations in cells/tissue. The development of drug-resistant cancer cells/tissues during chemotherapy is a major challenge in cancer treatment. In this paper, using a mouse model and PWS, the structural properties of tumor tissue grown in 3D structures by xenografting drug-resistant and drug-sensitive human prostate cancer cells having 2D structures, are studied. The results show that the 3D xenografted tissues maintain a similar hierarchy of the degree of structural disorder properties as that of the 2D original drug-sensitive and …

Novel Mechanistic Insight Into The Anticancer Activity Of Cucurbitacin D Against Pancreatic Cancer (Cuc D Attenuates Pancreatic Cancer), Mohammed Sikander, Shabnam Malik, Sheema Khan, Sonam Kumari, Neeraj Chauhan, Parvez Khan, Fathi T. Halaweish, Bhavin Chauhan, Murali M. Yallapu, Meena Jaggi, Subhash C. Chauhan

School of Medicine Publications

Pancreatic cancer (PanCa) is one of the leading causes of death from cancer in the United States. The current standard treatment for pancreatic cancer is gemcitabine, but its success is poor due to the emergence of drug resistance. Natural products have been widely investigated as potential candidates in cancer therapies, and cucurbitacin D (Cuc D) has shown excellent anticancer properties in various models. However, there is no report on the therapeutic effect of Cuc D in PanCa. In the present study, we investigated the effects of the Cuc D on PanCa cells in vitro and in vivo. Cuc D inhibited …

Cordycepin Inhibits Human Ovarian Cancer By Inducing Autophagy And Apoptosis Through Dickkopf-Related Protein 1/Β-Catenin Signaling, Hyun-Jin Jang, Kyeong Eun Yang, In-Hu Hwang, Yang Hoon Huh, Dae Joon Kim, Hwa-Seung Yoo, Soo Jung Park, Ik-Soon Jang

School of Medicine Publications

Cordycepin, the major active component from Cordyceps militaris, has been reported to significantly inhibit some types of cancer; however, its effects on ovarian cancer are still not well understood. In this study, we treated human ovarian cancer cells with different doses of cordycepin and found that it dose-dependently reduced ovarian cancer cell viability, based on Cell counting kit-8 reagent. Immunoblotting showed that cordycepin increased Dickkopf-related protein 1 (Dkk1) levels and inhibited β-catenin signaling. Atg7 knockdown in ovarian cancer cells significantly inhibited cordycepin-induced apoptosis, whereas β-catenin overexpression abolished the effects of cordycepin on cell death and proliferation. Furthermore, we found …

Gemcitabine Combination Nano Therapies For Pancreatic Cancer, Kamalika Samanta, Saini Setua, Sonam Kumari, Meena Jaggi, Murali Yallapu, Subhash C. Chauhan

School of Medicine Publications

Pancreatic cancer is one of the deadliest causes of cancer-related death in the United States, with a 5-year overall survival rate of 6 to 8%. These statistics suggest that immediate medical attention is needed. Gemcitabine (GEM) is the gold standard first-line single chemotherapy agent for pancreatic cancer but, after a few months, cells develop chemoresistance. Multiple clinical and experimental investigations have demonstrated that a combination or co-administration of other drugs as chemotherapies with GEM lead to superior therapeutic benefits. However, such combination therapies often induce severe systemic toxicities. Thus, developing strategies to deliver a combination of chemotherapeutic agents more securely …

Isodeoxyelephantopin, A Sesquiterpene Lactone Induces Ros Generation, Suppresses Nf-Κb Activation, Modulates Lncrna Expression And Exhibit Activities Against Breast Cancer, Sumit S. Verma, Vipin Rai, Nikee Awasthee, Anupam Dhasmana, Dhanya S. Rajalaksmi, Mangalam S. Nair, Subash C. Gupta

School of Medicine Publications

The sesquiterpene lactones, Isodeoxyelephantopin (IDET) and Deoxyelephantopin (DET) are known to exhibit activities against some cancer types. The activities of these lactones against breast cancer and the molecular bases is not known. We examined the efficacy of lactones in breast cancer preclinical model. Although both lactones exhibited drug like properties, IDET was relatively effective in comparison to DET. IDET suppressed the proliferation of both invasive and non-invasive breast cancer cell lines. IDET also suppressed the colony formation and migration of breast cancer cells. The assays for Acridine Orange (AO)/Propidium Iodide (PI) staining, cell cycle distribution, phosphatidylserine externalization and DNA laddering …

Fine Mapping And Identification Of Serum Urate Loci In American Indians: The Strong Heart Family Study, Geetha Chittoor, Karin Haack, Poojitha Balakrishnan, Christopher Bizon, Sandra Laston, Lyle G. Best, Jean W. Maccluer, Kari E. North, Jason G. Umans

School of Medicine Publications

While studies have reported genetic loci affecting serum urate (SU) concentrations, few studies have been conducted in minority populations. Our objective for this study was to identify genetic loci regulating SU in a multigenerational family-based cohort of American Indians, the Strong Heart Family Study (SHFS). We genotyped 162,718 single nucleotide polymorphisms (SNPs) in 2000 SHFS participants using an Illumina MetaboChip array. A genome-wide association analysis of SU was conducted using measured genotype analysis approach accounting for kinships in SOLAR, and meta-analysis in METAL. Our results showed strong association of SU with rs4481233, rs9998811, rs7696092 and rs13145758 (minor allele frequency (MAF) …

Genetic Variants Affecting Bone Mineral Density And Bone Mineral Content At Multiple Skeletal Sites In Hispanic Children, Ruixue Hou, Shelley A. Cole, Mariaelisa Graff, Karin Haack, Sandra Laston, Anthony G. Comuzzie, Nitesh R. Mehta, Kathleen Ryan, Diana L. Cousminer, Babette S. Zemel

School of Medicine Publications

Context:

Osteoporosis is a major public health burden with significant economic costs. However, the correlates of bone health in Hispanic children are understudied.

Objective:

We aimed to identify genetic variants associated with bone mineral density (BMD) and bone mineral content (BMC) at multiple skeletal sites in Hispanic children.

Methods:

We conducted a cross-sectional genome-wide linkage analysis, genome-wide and exome-wide association analysis of BMD and BMC. The Viva La Familia Study is a family-based cohort with a total of 1,030 Hispanic children (4–19 years old at baseline) conducted in Houston, TX. BMD and BMC were measured by Dual-energy X-ray absorptiometry.

Results: …

A Proposal For Complementarity Between Migration And Psychoanalytical Studies In Mental Health [Una Propuesta De Complementariedad Entre Los Estudios De Migración Y Psicoanalíticos En Salud Mental], Ángel Luna, Silvia Mejia-Arango

School of Medicine Publications

The objective of this article is to discuss the epistemological foundations of psychoanalytic studies and their possibility of complementarity with migration studies based on sociology. The methodology used was the review of theoretical production about epistemology in psychoanalysis, the tradition of research in sociology, as well the migration studies focused on mental health. Among the results, important epistemological and methodological coincidences between both disciplines were found. From this, a brief proposal is presented that highlights the feasibility of generating complementary studies on migration, specifically in border contexts. It is argued that the value of this article lies in the exploration …

Corneal Refractive Surgery In Patients With History Of Optic Neuritis, Majid Moshirfar, William D. Wagner, Steven H. Linn, Tanner W. Brown, Jackson L. Goldberg, Aaron T. Gomez, Yasmyne C. Ronquillo, Phillip C. Hoopes

School of Medicine Publications

Purpose

The purpose of this study was to evaluate the risk of recurrence of optic neuritis after corneal refractive surgery in patients with a history of optic neuritis and to examine the safety and efficacy of the procedure in this population.

Methods

This was a retrospective chart review of patients with a history of optic neuritis who underwent laser-assisted in situ keratomileusis (LASIK) or photorefractive keratectomy (PRK) at a single tertiary center from June 1996 to December 2014. Fifteen eyes of 14 patients were included in this study. Visual acuity before and after the surgery was recorded. Patients were followed-up …

Cross-Linked Polyphenol-Based Drug Nano-Self-Assemblies Engineered To Blockade Prostate Cancer Senescence, Prashanth K.B. Nagesh, Pallabita Chowdhury, Elham Hatami, Sonam Kumari, Vivek K. Kashyap, Manish Tripathi, Santosh Wagh, Bernd Meibohm, Subhash C. Chauhan, Meena Jaggi, Murali M. Yallapu

School of Medicine Publications

Cellular senescence is one of the prevailing issues in cancer therapeutics that promotes cancer relapse, chemoresistance, and recurrence. Patients undergoing persistent chemotherapy often develop drug-induced senescence. Docetaxel, an FDA-approved treatment for prostate cancer, is known to induce cellular senescence which often limits the overall survival of patients. Strategic therapies that counter the cellular and drug-induced senescence are an unmet clinical need. Towards this an effort was made to develop a novel therapeutic strategy that targets and removes senescent cells from the tumors, we developed a nanoformulation of tannic acid−docetaxel self-assemblies (DSAs). The construction of DSAs was confirmed through particle size …