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Using Implementation Mapping To Increase Uptake And Use Of Salud En Mis Manos: A Breast And Cervical Cancer Screening And Hpv Vaccination Intervention For Latinas, Lara S Savas, Preena Loomba, Ross Shegog, Angelita Alaniz, Crystal Costa, Emily Adlparvar, Marlyn A Allicock, Roshanda Chenier, Margaret Goetz, Christine M Markham, Maria E Fernandez Jan 2023

Using Implementation Mapping To Increase Uptake And Use Of Salud En Mis Manos: A Breast And Cervical Cancer Screening And Hpv Vaccination Intervention For Latinas, Lara S Savas, Preena Loomba, Ross Shegog, Angelita Alaniz, Crystal Costa, Emily Adlparvar, Marlyn A Allicock, Roshanda Chenier, Margaret Goetz, Christine M Markham, Maria E Fernandez

Faculty, Staff and Student Publications

BACKGROUND: Despite CDC recommendations for breast and cervical cancer screening and HPV vaccination, cancer control behaviors are underutilized among low-income Latinas.

METHODS: We used Implementation Mapping to create SEMM-Dissemination and Implementation Assistance (SEMM-DIA), a set of implementation strategies designed to support implementation and maintenance of SEMM in clinic settings. Specifically, we used Implementation Mapping's five iterative tasks to guide the use of theories and frameworks, evidence, new data, and stakeholder input to develop strategies to accelerate and improve implementation fidelity, reach, and maintenance of the SEMM intervention. The resulting implementation mapping logic model also guides the SEMM-DIA evaluation plan to …


Genome-Wide Mendelian Randomization Identifies Putatively Causal Gut Microbiota For Multiple Peptic Ulcer Diseases, Jingwei Zhao, Yucheng Hou, Tianyi Xie, Yizhang Zhu, Xinyi Feng, Yong Zhang, Ziyi Yang, Wei Gong Jan 2023

Genome-Wide Mendelian Randomization Identifies Putatively Causal Gut Microbiota For Multiple Peptic Ulcer Diseases, Jingwei Zhao, Yucheng Hou, Tianyi Xie, Yizhang Zhu, Xinyi Feng, Yong Zhang, Ziyi Yang, Wei Gong

Faculty, Staff and Student Publications

OBJECTIVE: The pathogenesis of peptic ulcer diseases (PUDs) involves multiple factors, and the contribution of gut microbiota to this process remains unclear. While previous studies have associated gut microbiota with peptic ulcers, the precise nature of the relationship, whether causal or influenced by biases, requires further elucidation.

DESIGN: The largest meta-analysis of genome-wide association studies was conducted by the MiBioGen consortium, which provided the summary statistics of gut microbiota for implementation in the Mendelian randomization (MR) analysis. Summary statistics for five types of PUDs were compiled using the FinnGen Consortium R8 release data. Various statistical techniques, including inverse variance weighting …


Whole Genome Sequence Analysis Of Apparent Treatment Resistant Hypertension Status In Participants From The Trans-Omics For Precision Medicine Program, Nicole D Armstrong, Vinodh Srinivasasainagendra, Farah Ammous, Themistocles L Assimes, Amber L Beitelshees, Jennifer Brody, Brian E Cade, Yii-Der Ida Chen, Han Chen, Paul S De Vries, James S Floyd, Nora Franceschini, Xiuqing Guo, Jacklyn N Hellwege, John S House, Chii-Min Hwu, Sharon L R Kardia, Ethan M Lange, Leslie A Lange, Caitrin W Mcdonough, May E Montasser, Jeffrey R O'Connell, Megan M Shuey, Xiao Sun, Rikki M Tanner, Zhe Wang, Wei Zhao, April P Carson, Todd L Edwards, Tanika N Kelly, Eimear E Kenny, Charles Kooperberg, Ruth J F Loos, Alanna C Morrison, Alison Motsinger-Reif, Bruce M Psaty, Dabeeru C Rao, Susan Redline, Stephen S Rich, Jerome I Rotter, Jennifer A Smith, Albert V Smith, Marguerite R Irvin, Donna K Arnett Jan 2023

Whole Genome Sequence Analysis Of Apparent Treatment Resistant Hypertension Status In Participants From The Trans-Omics For Precision Medicine Program, Nicole D Armstrong, Vinodh Srinivasasainagendra, Farah Ammous, Themistocles L Assimes, Amber L Beitelshees, Jennifer Brody, Brian E Cade, Yii-Der Ida Chen, Han Chen, Paul S De Vries, James S Floyd, Nora Franceschini, Xiuqing Guo, Jacklyn N Hellwege, John S House, Chii-Min Hwu, Sharon L R Kardia, Ethan M Lange, Leslie A Lange, Caitrin W Mcdonough, May E Montasser, Jeffrey R O'Connell, Megan M Shuey, Xiao Sun, Rikki M Tanner, Zhe Wang, Wei Zhao, April P Carson, Todd L Edwards, Tanika N Kelly, Eimear E Kenny, Charles Kooperberg, Ruth J F Loos, Alanna C Morrison, Alison Motsinger-Reif, Bruce M Psaty, Dabeeru C Rao, Susan Redline, Stephen S Rich, Jerome I Rotter, Jennifer A Smith, Albert V Smith, Marguerite R Irvin, Donna K Arnett

Faculty, Staff and Student Publications

Introduction: Apparent treatment-resistant hypertension (aTRH) is characterized by the use of four or more antihypertensive (AHT) classes to achieve blood pressure (BP) control. In the current study, we conducted single-variant and gene-based analyses of aTRH among individuals from 12 Trans-Omics for Precision Medicine cohorts with whole-genome sequencing data.

Methods: Cases were defined as individuals treated for hypertension (HTN) taking three different AHT classes, with average systolic BP ≥ 140 or diastolic BP ≥ 90 mmHg, or four or more medications regardless of BP (n = 1,705). A normotensive control group was defined as individuals with BP < 140/90 mmHg (n = 22,079), not on AHT medication. A second control group comprised individuals who were treatment responsive on one AHT medication with BP < 140/ 90 mmHg (n = 5,424). Logistic regression with kinship adjustment using the Scalable and Accurate Implementation of Generalized mixed models (SAIGE) was performed, adjusting for age, sex, and genetic ancestry. We assessed variants using SKAT-O in rare-variant analyses. Single-variant and gene-based tests were conducted in a pooled multi-ethnicity stratum, as well as self-reported ethnic/racial strata (European and African American).

Results: One variant in …


P120-Catenin Subfamily Members Have Distinct As Well As Shared Effects On Dendrite Morphology During Neuron Development In Vitro, Maxsam S Donta, Yogesh Srivastava, Christina M Di Mauro, Adriana Paulucci-Holthauzen, M Neal Waxham, Pierre D Mccrea Jan 2023

P120-Catenin Subfamily Members Have Distinct As Well As Shared Effects On Dendrite Morphology During Neuron Development In Vitro, Maxsam S Donta, Yogesh Srivastava, Christina M Di Mauro, Adriana Paulucci-Holthauzen, M Neal Waxham, Pierre D Mccrea

Faculty, Staff and Student Publications

Dendritic arborization is essential for proper neuronal connectivity and function. Conversely, abnormal dendrite morphology is associated with several neurological pathologies like Alzheimer's disease and schizophrenia. Among major intrinsic mechanisms that determine the extent of the dendritic arbor is cytoskeletal remodeling. Here, we characterize and compare the impact of the four proteins involved in cytoskeletal remodeling-vertebrate members of the p120-catenin subfamily-on neuronal dendrite morphology. In relation to each of their own distributions, we find that p120-catenin and delta-catenin are expressed at relatively higher proportions in growth cones compared to ARVCF-catenin and p0071-catenin; ARVCF-catenin is expressed at relatively high proportions in the …


Effect Of "Maccog" Tcm Tea On Improving Glucolipid Metabolism And Gut Microbiota In Patients With Type 2 Diabetes In Community, Biyue Hu, Tongtong Yin, Jiajia Zhang, Minjing Liu, Hang Yun, Jian Wang, Renmei Guo, Jie Huang, Yixia Zhou, Hongyan Meng, Li Wang Jan 2023

Effect Of "Maccog" Tcm Tea On Improving Glucolipid Metabolism And Gut Microbiota In Patients With Type 2 Diabetes In Community, Biyue Hu, Tongtong Yin, Jiajia Zhang, Minjing Liu, Hang Yun, Jian Wang, Renmei Guo, Jie Huang, Yixia Zhou, Hongyan Meng, Li Wang

Faculty, Staff and Student Publications

OBJECTIVES: This work aimed to observe the effect of consuming Chinese herb tea on glucolipid metabolism and gut microbiota in patients with type 2 diabetes mellitus (T2DM).

METHODS: Ninety patients with T2DM were recruited from a community and randomly divided into the control group (CG) and intervention group (IG). CG maintained conventional treatment and lifestyle, and IG accepted additional "maccog" traditional Chinese medicine (TCM) tea (mulberry leaf, radix astragali, corn stigma, cortex lycii, radix ophiopogonis, and gynostemma) for 12 weeks. Glucolipid metabolism, hepatorenal function, and gut microbiota were then measured.

RESULTS: After the intervention, the decreases in fasting plasma glucose …


Reimbursement For Hpv Vaccine Cost In The Private Sector: A Comparison Across Specialties, Yenan Zhu, Yueh-Yun Lin, Ruosha Li, Cara He, David R Lairson, Ashish A Deshmukh, Kalyani Sonawane Jan 2023

Reimbursement For Hpv Vaccine Cost In The Private Sector: A Comparison Across Specialties, Yenan Zhu, Yueh-Yun Lin, Ruosha Li, Cara He, David R Lairson, Ashish A Deshmukh, Kalyani Sonawane

Faculty, Staff and Student Publications

The human papillomavirus (HPV) vaccine is the most expensive of all routinely recommended pediatric vaccines. Adequate cost reimbursement by 3rd-party payers is a critical enabling factor for clinicians to continue offering vaccines. This study found that net returns from HPV vaccine cost reimbursements are lowest for family physicians ($0.34/dose) and highest for pediatricians ($5.08/dose). Furthermore, a $1 increment in return was associated with an increase in HPV vaccine doses administered (highest for family physicians; 0.08% per dollar). Reimbursement for HPV vaccine costs by private payers is adequate; however, return margins are small for non-pediatric specialties.


Susceptible Windows Of Exposure To Fine Particulate Matter And Fetal Growth Trajectories In The Spanish Inma (Infancia Y Medio Ambiente) Birth Cohort, Wei-Jen Chen, Alison M Rector, Monica Guxens, Carmen Iniguez, Michael D Swartz, Elaine Symanski, Jesús Ibarluzea, Albert Ambros, Marisa Estarlich, Aitana Lertxundi, Isolina Riano-Galán, Jordi Sunyer, Ana Fernandez-Somoano, Suneet P Chauhan, Jennifer Ish, Kristina W Whitworth Jan 2023

Susceptible Windows Of Exposure To Fine Particulate Matter And Fetal Growth Trajectories In The Spanish Inma (Infancia Y Medio Ambiente) Birth Cohort, Wei-Jen Chen, Alison M Rector, Monica Guxens, Carmen Iniguez, Michael D Swartz, Elaine Symanski, Jesús Ibarluzea, Albert Ambros, Marisa Estarlich, Aitana Lertxundi, Isolina Riano-Galán, Jordi Sunyer, Ana Fernandez-Somoano, Suneet P Chauhan, Jennifer Ish, Kristina W Whitworth

Faculty, Staff and Student Publications

While prior studies report associations between fine particulate matter (PM


Age-Induced Changes In Anti-Tumor Immunity Alter The Tumor Immune Infiltrate And Impact Response To Immuno-Oncology Treatments, Suzanne I Sitnikova, Jennifer A Walker, Laura B Prickett, Michelle Morrow, Viia E Valge-Archer, Matthew J Robinson, Robert W Wilkinson, Simon J Dovedi Jan 2023

Age-Induced Changes In Anti-Tumor Immunity Alter The Tumor Immune Infiltrate And Impact Response To Immuno-Oncology Treatments, Suzanne I Sitnikova, Jennifer A Walker, Laura B Prickett, Michelle Morrow, Viia E Valge-Archer, Matthew J Robinson, Robert W Wilkinson, Simon J Dovedi

Faculty, Staff and Student Publications

INTRODUCTION: Immuno-oncology (IO) research relies heavily on murine syngeneic tumor models. However, whilst the average age for a cancer diagnosis is 60 years or older, for practical purposes the majority of preclinical studies are conducted in young mice, despite the fact that ageing has been shown to have a significant impact on the immune response.

METHODS: Using aged (60-72 weeks old) mice bearing CT26 tumors, we investigated the impact of ageing on tumor growth as well as the immune composition of the tumor and peripheral lymphoid organs.

RESULTS: We found many differences in the immune cell composition of both the …


Methodological Considerations In Pisces 3: A Randomized, Placebo-Controlled Study Of Intracerebral Stem Cells In Subjects With Disability Following An Ischemic Stroke, Daniel T Laskowitz, Keith W Muir, Sean I Savitz, Lawrence R Wechsler, Julie G Pilitsis, Scott Y Rahimi, Richard L Beckman, Vincent Holmes, Peng R Chen, Laura Juel, Deborah Koltai, Brad J Kolls Jan 2023

Methodological Considerations In Pisces 3: A Randomized, Placebo-Controlled Study Of Intracerebral Stem Cells In Subjects With Disability Following An Ischemic Stroke, Daniel T Laskowitz, Keith W Muir, Sean I Savitz, Lawrence R Wechsler, Julie G Pilitsis, Scott Y Rahimi, Richard L Beckman, Vincent Holmes, Peng R Chen, Laura Juel, Deborah Koltai, Brad J Kolls

Faculty, Staff and Student Publications

Background and hypothesis: At present, there are no medical interventions proven to improve functional recovery in patients with subacute stroke. We hypothesize that the intraparenchymal administration of CTX0E03, a conditionally immortalized neural stem cell line, linked with a standardized rehabilitation therapy regimen for the upper limb, would improve functional outcomes in patients 6-12 months after an index ischemic stroke.

Study design: PISCES III was designed as a multicenter prospective, sham-controlled, outcome-blinded randomized clinical trial. Eligibility required a qualifying ischemic stroke 6-12 months prior to surgical intervention. Patients must be between 35 and 75 years of age and have residual moderate …


Editorial: The Impact Of Inflammation On The Oral Microbiome, Chun-Teh Lee, Loreto Abusleme, Thomas E Van Dyke Jan 2023

Editorial: The Impact Of Inflammation On The Oral Microbiome, Chun-Teh Lee, Loreto Abusleme, Thomas E Van Dyke

Faculty, Staff and Student Publications

No abstract provided.


Enabling Structural Resilience Of Street-Involved Children And Youth In Kenya: Reintegration Outcomes And The Flourishing Community Model, Michael L Goodman, Sarah E Seidel, Andrew Springer, Aleisha Elliott, Christine Markham, Hani Serag, Philip Keiser, Ben Raimer, Lauren Raimer-Goodman, Christine Gatwiri, Kelvin Munene, Stanley Gitari Jan 2023

Enabling Structural Resilience Of Street-Involved Children And Youth In Kenya: Reintegration Outcomes And The Flourishing Community Model, Michael L Goodman, Sarah E Seidel, Andrew Springer, Aleisha Elliott, Christine Markham, Hani Serag, Philip Keiser, Ben Raimer, Lauren Raimer-Goodman, Christine Gatwiri, Kelvin Munene, Stanley Gitari

Faculty, Staff and Student Publications

Introduction: Millions of children and youth live on city streets across the globe, vulnerable to substance use, abuse, material and structural neglect. Structural resilience, the re-establishment of access to structural goods within a society such as housing, education, and healthcare following some interruption, provides an orientation for research and interventional efforts with street-involved children and youth (SICY). Further, a structural resilience framework supports organizing interactions between levels and sectors of a socio-ecology.

Methods: Following the expressed interests of Kenyan SICY, and consistent with emerging policy interests at national and global levels, we assess reintegration trajectories of Kenyan SICY (n …


A Narrative Review Of The Lesser Known Medications For Treatment Of Restless Legs Syndrome And Pathogenetic Implications For Their Use, Paul G Yeh, Karen Spruyt, Lourdes M Delrosso, Arthur S Walters Jan 2023

A Narrative Review Of The Lesser Known Medications For Treatment Of Restless Legs Syndrome And Pathogenetic Implications For Their Use, Paul G Yeh, Karen Spruyt, Lourdes M Delrosso, Arthur S Walters

Faculty, Staff and Student Publications

BACKGROUND: There are several well-known treatments for Restless Legs Syndrome (RLS), including dopamine agonists (pramipexole, ropinirole, rotigotine), anticonvulsants (gabapentin and its analogs, pregabalin), oral or intravenous iron, opioids and benzodiazepines. However, in clinical practice, treatment is sometimes limited due to incomplete response or side effects and it is necessary to be aware of other treatment options for RLS, which is the purpose of this review.

METHODS: We performed a narrative review detailing all of the lesser known pharmacological treatment literature on RLS. The review purposefully excludes well-established, well-known treatments for RLS which are widely accepted as treatments for RLS in …


The Predictive Value Of Coronary Microvascular Dysfunction For Left Ventricular Reverse Remodelling In Dilated Cardiomyopathy, Ao Kan, Yinping Leng, Shuhao Li, Fang Lin, Qimin Fang, Xinwei Tao, Mengyao Hu, Lianggeng Gong Jan 2023

The Predictive Value Of Coronary Microvascular Dysfunction For Left Ventricular Reverse Remodelling In Dilated Cardiomyopathy, Ao Kan, Yinping Leng, Shuhao Li, Fang Lin, Qimin Fang, Xinwei Tao, Mengyao Hu, Lianggeng Gong

Faculty, Staff and Student Publications

AIMS: to evaluate the degree of coronary microvascular dysfunction (CMD) in dilated cardiomyopathy (DCM) patients by cardiac magnetic resonance (CMR) first-pass perfusion parameters and to examine the correlation between myocardial perfusion and left ventricle reverse remodelling (LVRR).

METHODS: In this study, 94 DCM patients and 35 healthy controls matched for age and sex were included. Myocardial perfusion parameters, including upslope, time to maximum signal intensity (Time

RESULTS: With a median follow-up period of 12 months [interquartile range (IQR), 8-13], 41 DCM patients (44%) achieved LVRR. Compared with healthy controls, DCM patients presented CMD with reduced upslope, SI

CONCLUSIONS: CMD could …


Cd73-Generated Extracellular Adenosine Promotes Resolution Of Neutrophil-Mediated Tissue Injury And Restrains Metaplasia In Pancreatitis, Baylee J O'Brien, Erika Y Faraoni, Lincoln N Strickland, Zhibo Ma, Victoria Mota, Samantha Mota, Xuebo Chen, Tingting Mills, Holger K Eltzschig, Kathleen E Delgiorno, Jennifer M Bailey-Lundberg Jan 2023

Cd73-Generated Extracellular Adenosine Promotes Resolution Of Neutrophil-Mediated Tissue Injury And Restrains Metaplasia In Pancreatitis, Baylee J O'Brien, Erika Y Faraoni, Lincoln N Strickland, Zhibo Ma, Victoria Mota, Samantha Mota, Xuebo Chen, Tingting Mills, Holger K Eltzschig, Kathleen E Delgiorno, Jennifer M Bailey-Lundberg

Faculty, Staff and Student Publications

Pancreatitis is currently the leading cause of gastrointestinal hospitalizations in the US. This condition occurs in response to abdominal injury, gallstones, chronic alcohol consumption or, less frequently, the cause remains idiopathic. CD73 is a cell surface ecto‐5′‐nucleotidase that generates extracellular adenosine, which can contribute to resolution of inflammation by binding adenosine receptors on infiltrating immune cells. We hypothesized genetic deletion of CD73 would result in more severe pancreatitis due to decreased generation of extracellular adenosine. CD73 knockout (CD73 −/−) and C57BL/6 (wild type, WT) mice were used to evaluate the progression and response of caerulein‐induced acute and chronic pancreatitis. …


Tp53-Pten-Nf1 Depletion In Human Brain Organoids Produces A Glioma Phenotype In Vitro, Sanjay K Singh, Yan Wang, Ahmed Habib, Mamindla Priyadarshini, Chowdari V Kodavali, Apeng Chen, Wencai Ma, Jing Wang, N U Farrukh Hameed, Baoli Hu, Gregory N Fuller, Scott M Kulich, Nduka Amankulor, Rivka R Colen, Lincoln A Edwards, Pascal O Zinn Jan 2023

Tp53-Pten-Nf1 Depletion In Human Brain Organoids Produces A Glioma Phenotype In Vitro, Sanjay K Singh, Yan Wang, Ahmed Habib, Mamindla Priyadarshini, Chowdari V Kodavali, Apeng Chen, Wencai Ma, Jing Wang, N U Farrukh Hameed, Baoli Hu, Gregory N Fuller, Scott M Kulich, Nduka Amankulor, Rivka R Colen, Lincoln A Edwards, Pascal O Zinn

Faculty, Staff and Student Publications

Glioblastoma (GBM) is fatal and the study of therapeutic resistance, disease progression, and drug discovery in GBM or glioma stem cells is often hindered by limited resources. This limitation slows down progress in both drug discovery and patient survival. Here we present a genetically engineered human cerebral organoid model with a cancer-like phenotype that could provide a basis for GBM-like models. Specifically, we engineered a doxycycline-inducible vector encoding shRNAs enabling depletion of the TP53, PTEN, and NF1 tumor suppressors in human cerebral organoids. Designated as inducible short hairpin-TP53-PTEN-NF1 (ish-TPN), doxycycline treatment resulted in human cancer-like cerebral organoids that effaced the …


Association Of Cyclooxygenase-2 Expression With Endoplasmic Reticulum Stress And Autophagy In Triple-Negative Breast Cancer, Haechan Lee, Sungwook Jung, Gyungyub Gong, Bora Lim, Hee Jin Lee Jan 2023

Association Of Cyclooxygenase-2 Expression With Endoplasmic Reticulum Stress And Autophagy In Triple-Negative Breast Cancer, Haechan Lee, Sungwook Jung, Gyungyub Gong, Bora Lim, Hee Jin Lee

Faculty, Staff and Student Publications

Cyclooxygenase-2 plays a role in oncogenesis and its overexpression is associated with triple-negative breast cancer. However, the mechanisms whereby cyclooxygenase-2 contribute to breast cancer are complex and not well understood. Cyclooxygenase-2 overexpression causes hypoxia, oxidative stress, and endoplasmic reticulum stress. The aim of this study is to investigate the correlations among cyclooxygenase-2 expression, endoplasmic reticulum stress-associated molecules, and autophagy-associated molecules in triple-negative breast cancer. Surgical specimens from two cohorts of triple-negative breast cancer patients without neoadjuvant systemic therapy were analyzed: cohorts 1 and 2 consisted of 218 cases from 2004 to 2006 and 221 cases from 2007 to 2009, respectively. …


Circadian Rhythms Of Risk Factors And Management In Atherosclerotic And Hypertensive Vascular Disease: Modern Chronobiological Perspectives Of An Ancient Disease, Yong-Jian Geng, Michael H Smolensky, Oliver Sum-Ping, Ramon Hermida, Richard J Castriotta Jan 2023

Circadian Rhythms Of Risk Factors And Management In Atherosclerotic And Hypertensive Vascular Disease: Modern Chronobiological Perspectives Of An Ancient Disease, Yong-Jian Geng, Michael H Smolensky, Oliver Sum-Ping, Ramon Hermida, Richard J Castriotta

Faculty, Staff and Student Publications

Atherosclerosis, a chronic inflammatory disease of the arteries that appears to have been as prevalent in ancient as in modern civilizations, is predisposing to life-threatening and life-ending cardiac and vascular complications, such as myocardial and cerebral infarctions. The pathogenesis of atherosclerosis involves intima plaque buildup caused by vascular endothelial dysfunction, cholesterol deposition, smooth muscle proliferation, inflammatory cell infiltration and connective tissue accumulation. Hypertension is an independent and controllable risk factor for atherosclerotic cardiovascular disease (CVD). Conversely, atherosclerosis hardens the arterial wall and raises arterial blood pressure. Many CVD patients experience both atherosclerosis and hypertension and are prescribed medications to concurrently …


Clinical Manifestations And Outcome Of Patients With Primary Amoebic Meningoencephalitis In Pakistan. A Single-Center Experience, Shakeel Ur Rehman, Salman Farooq, Muhammad Bilal Tariq, Nosheen Nasir, Mohammad Wasay, Sobia Masood, Musa Karim Jan 2023

Clinical Manifestations And Outcome Of Patients With Primary Amoebic Meningoencephalitis In Pakistan. A Single-Center Experience, Shakeel Ur Rehman, Salman Farooq, Muhammad Bilal Tariq, Nosheen Nasir, Mohammad Wasay, Sobia Masood, Musa Karim

Faculty, Staff and Student Publications

Primary amoebic meningoencephalitis (PAM) is a rapidly progressing central nervous system (CNS) infection caused by Naegleria fowleri, a free-living amoeba found in warm freshwater. The disease progression is very rapid, and the outcome is nearly always fatal. We aim to describe the disease course in patients admitted with PAM in a tertiary care center in Karachi, Pakistan between the periods of 2010 to 2021. A total of 39 patients were included in the study, 33 males (84.6%). The median age of the patients was 34 years. The most frequent presenting complaint was fever, which was found in 37 patients (94.9%) …


Challenges And Promise Of Targeting Mirrna In Rheumatic Diseases: A Computational Approach To Identify Mirna Association With Cell Types, Cytokines, And Disease Mechanisms, Farheen S Shaikh, Ruby J Siegel, Aayush Srivastava, David A Fox, Salahuddin Ahmed Jan 2023

Challenges And Promise Of Targeting Mirrna In Rheumatic Diseases: A Computational Approach To Identify Mirna Association With Cell Types, Cytokines, And Disease Mechanisms, Farheen S Shaikh, Ruby J Siegel, Aayush Srivastava, David A Fox, Salahuddin Ahmed

Faculty, Staff and Student Publications

MicroRNAs (miRNAs) are small non-coding RNAs that alter the expression of target genes at the post-transcriptional level, influencing diverse outcomes in metabolism, cell differentiation, proliferation, cell survival, and cell death. Dysregulated miRNA expression is implicated in various rheumatic conditions, including ankylosing spondylitis (AS), gout, juvenile idiopathic arthritis (JIA), osteoarthritis (OA), psoriatic arthritis, rheumatoid arthritis (RA), Sjogren's syndrome, systemic lupus erythematosus (SLE) and systemic sclerosis. For this review, we used an open-source programming language- PowerShell, to scan the massive number of existing primary research publications on PubMed on miRNAs in these nine diseases to identify and count unique co-occurrences of individual …


In Utero Ethanol Exposure Induces Mitochondrial Dna Damage And Inhibits Mtdna Repair In Developing Brain, Nune Darbinian, Armine Darbinyan, Nana Merabova, Myrna Kassem, Gabriel Tatevosian, Shohreh Amini, Laura Goetzl, Michael E Selzer Jan 2023

In Utero Ethanol Exposure Induces Mitochondrial Dna Damage And Inhibits Mtdna Repair In Developing Brain, Nune Darbinian, Armine Darbinyan, Nana Merabova, Myrna Kassem, Gabriel Tatevosian, Shohreh Amini, Laura Goetzl, Michael E Selzer

Faculty, Staff and Student Publications

Introduction

Mitochondrial dysfunction is postulated to be a central event in fetal alcohol spectrum disorders (FASD). People with the most severe form of FASD, fetal alcohol syndrome (FAS) are estimated to live only 34 years (95% confidence interval, 31 to 37 years), and adults who were born with any form of FASD often develop early aging. Mitochondrial dysfunction and mitochondrial DNA (mtDNA) damage, hallmarks of aging, are postulated central events in FASD. Ethanol (EtOH) can cause mtDNA damage, consequent increased oxidative stress, and changes in the mtDNA repair protein 8-oxoguanine DNA glycosylase-1 (OGG1). Studies of molecular mechanisms are limited by …


Stellettin B Sensitizes Glioblastoma To Dna-Damaging Treatments By Suppressing Pi3k-Mediated Homologous Recombination Repair, Xin Peng, Shaolu Zhang, Yingying Wang, Zhicheng Zhou, Zixiang Yu, Zhenxing Zhong, Liang Zhang, Zhe-Sheng Chen, Francois X Claret, Moshe Elkabets, Feng Wang, Fan Sun, Ran Wang, Han Liang, Hou-Wen Lin, Dexin Kong Jan 2023

Stellettin B Sensitizes Glioblastoma To Dna-Damaging Treatments By Suppressing Pi3k-Mediated Homologous Recombination Repair, Xin Peng, Shaolu Zhang, Yingying Wang, Zhicheng Zhou, Zixiang Yu, Zhenxing Zhong, Liang Zhang, Zhe-Sheng Chen, Francois X Claret, Moshe Elkabets, Feng Wang, Fan Sun, Ran Wang, Han Liang, Hou-Wen Lin, Dexin Kong

Faculty, Staff and Student Publications

Glioblastoma (GBM) is the most aggressive type of cancer. Its current first-line postsurgery regimens are radiotherapy and temozolomide (TMZ) chemotherapy, both of which are DNA damage-inducing therapies but show very limited efficacy and a high risk of resistance. There is an urgent need to develop novel agents to sensitize GBM to DNA-damaging treatments. Here it is found that the triterpene compound stellettin B (STELB) greatly enhances the sensitivity of GBM to ionizing radiation and TMZ in vitro and in vivo. Mechanistically, STELB inhibits the expression of homologous recombination repair (HR) factors BRCA1/2 and RAD51 by promoting the degradation of PI3Kα …


Editorial: The Interplay Between Microbiota And Allergen In Shaping Respiratory Mucosa Immunity: Role In Development Of Asthma, Zhenwei Xia, Wenwei Zhong, Min Wu, Scott E Evans Jan 2023

Editorial: The Interplay Between Microbiota And Allergen In Shaping Respiratory Mucosa Immunity: Role In Development Of Asthma, Zhenwei Xia, Wenwei Zhong, Min Wu, Scott E Evans

Faculty, Staff and Student Publications

No abstract provided.


A Large Screen Identifies Beta-Lactam Antibiotics Which Can Be Repurposed To Target The Syphilis Agent, Kathryn A Hayes, Jules M Dressler, Steven J Norris, Diane G Edmondson, Brandon L Jutras Jan 2023

A Large Screen Identifies Beta-Lactam Antibiotics Which Can Be Repurposed To Target The Syphilis Agent, Kathryn A Hayes, Jules M Dressler, Steven J Norris, Diane G Edmondson, Brandon L Jutras

Faculty, Staff and Student Publications

Syphilis, caused by the spirochete Treponema pallidum subsp. pallidum (hereafter called T. pallidum), is re-emerging as a worldwide sexually transmitted infection. A single intramuscular dose of benzathine penicillin G is the preferred syphilis treatment option. Both supply shortage concerns and the potential for acquired antibiotic resistance further the need to broaden the repertoire of syphilis therapeutics. We reasoned that other β-lactams may be equally or more effective at targeting the disease-causing agent, Treponema pallidum, but have yet to be discovered due to a previous lack of a continuous in vitro culture system. Recent technical advances with respect to …


Clonal Isolates Of Treponema Pallidum Subsp Pallidum Nichols Provide Evidence For The Occurrence Of Microevolution During Experimental Rabbit Infection And In Vitro Culture, Diane G Edmondson, Bridget D De Lay, Blake M Hanson, Lindsay E Kowis, Steven J Norris Jan 2023

Clonal Isolates Of Treponema Pallidum Subsp Pallidum Nichols Provide Evidence For The Occurrence Of Microevolution During Experimental Rabbit Infection And In Vitro Culture, Diane G Edmondson, Bridget D De Lay, Blake M Hanson, Lindsay E Kowis, Steven J Norris

Faculty, Staff and Student Publications

The recent development of a system for long-term in vitro culture of the syphilis spirochete, Treponema pallidum subsp. pallidum, has introduced the possibility of detailed genetic analysis of this bacterium. In this study, the in vitro culture system was used to isolate and characterize clonal populations of T. pallidum subsp. pallidum Nichols, the most widely studied strain. In limiting dilutions experiments, it was possible to establish cultures with inocula as low as 0.5 T. pallidum per well despite the long generation time (~35 to 40 hours) of this organism. Six Nichols strain clones isolated by limiting dilution were characterized in …


A Decade Of Blood-Brain Barrier Permeability Assays: Revisiting Old Traumatic Brain Injury Rat Data For New Insights And Experimental Design, Chris T Bolden, Scott D Olson, Charles S Cox Jan 2023

A Decade Of Blood-Brain Barrier Permeability Assays: Revisiting Old Traumatic Brain Injury Rat Data For New Insights And Experimental Design, Chris T Bolden, Scott D Olson, Charles S Cox

Faculty, Staff and Student Publications

Increased microvascular permeability at the level of the blood-brain barrier (BBB) often leads to vasogenic brain edema following traumatic brain injury (TBI). These pathologic conditions compromise the integrity of the neurovascular unit resulting in severe brain dysfunction. To quantify this permeability and assess ionic equillibrium, preclinical researchers have relied on the use of various molecular weight permeable dyes such as Evans Blue that normally cannot enter the brain parenchyma under homeostatic conditions. Evans Blue, the most cited of the molecular weight dyes, has reported reproducibility issues because of harsh extraction processes, suboptimal detection via absorbance, and wide excitation fluorescence spectra …


Bacterial Meningitis In Africa, Tatiana Barichello, Carlos Henrique Rocha Catalão, Ursula K Rohlwink, Martijn Van Der Kuip, Dan Zaharie, Regan S Solomons, Ronald Van Toorn, Marceline Tutu Van Furth, Rodrigo Hasbun, Federico Iovino, Vivian Ssonko Namale Jan 2023

Bacterial Meningitis In Africa, Tatiana Barichello, Carlos Henrique Rocha Catalão, Ursula K Rohlwink, Martijn Van Der Kuip, Dan Zaharie, Regan S Solomons, Ronald Van Toorn, Marceline Tutu Van Furth, Rodrigo Hasbun, Federico Iovino, Vivian Ssonko Namale

Faculty, Staff and Student Publications

Bacterial meningitis differs globally, and the incidence and case fatality rates vary by region, country, pathogen, and age group; being a life-threatening disease with a high case fatality rate and long-term complications in low-income countries. Africa has the most significant prevalence of bacterial meningitis illness, and the outbreaks typically vary with the season and the geographic location, with a high incidence in the meningitis belt of the sub-Saharan area from Senegal to Ethiopia. Streptococcus pneumoniae (pneumococcus) and Neisseria meningitidis (meningococcus) are the main etiological agents of bacterial meningitis in adults and children above the age of one. Streptococcus agalactiae (group …


Imaging Peripheral Lymphatic Dysfunction In Chronic Conditions, Eva M Sevick-Muraca, Caroline E Fife, John C Rasmussen Jan 2023

Imaging Peripheral Lymphatic Dysfunction In Chronic Conditions, Eva M Sevick-Muraca, Caroline E Fife, John C Rasmussen

Faculty, Staff and Student Publications

The lymphatics play important roles in chronic diseases/conditions that comprise the bulk of healthcare worldwide. Yet the ability to routinely image and diagnose lymphatic dysfunction, using commonly available clinical imaging modalities, has been lacking and as a result, the development of effective treatment strategies suffers. Nearly two decades ago, investigational near-infrared fluorescence lymphatic imaging and ICG lymphography were developed as routine diagnostic for clinically evaluating, quantifying, and treating lymphatic dysfunction in cancer-related and primary lymphedema, chronic venous disease, and more recently, autoimmune and neurodegenerative disorders. In this review, we provide an overview of what these non-invasive technologies have taught us …


A Deep Residual Model For Characterization Of 5d Spatiotemporal Network Dynamics Reveals Widespread Spatiodynamic Changes In Schizophrenia, Behnam Kazemivash, Theo G M Van Erp, Peter Kochunov, Vince D Calhoun Jan 2023

A Deep Residual Model For Characterization Of 5d Spatiotemporal Network Dynamics Reveals Widespread Spatiodynamic Changes In Schizophrenia, Behnam Kazemivash, Theo G M Van Erp, Peter Kochunov, Vince D Calhoun

Faculty, Staff and Student Publications

Schizophrenia is a severe brain disorder with serious symptoms including delusions, disorganized speech, and hallucinations that can have a long-term detrimental impact on different aspects of a patient's life. It is still unclear what the main cause of schizophrenia is, but a combination of altered brain connectivity and structure may play a role. Neuroimaging data has been useful in characterizing schizophrenia, but there has been very little work focused on voxel-wise changes in multiple brain networks over time, despite evidence that functional networks exhibit complex spatiotemporal changes over time within individual subjects. Recent studies have primarily focused on static (average) …


Processing Speed – A Potential Candidate Cognitive Endophenotype For Bipolar Disorder, Mirona Letitia Dobri, Taya Prince, Alexandre Paim Diaz, Giovana B Zunta-Soares, Sudhakar Selvaraj, Rodrigo Machado-Vieira, Thomas D Meyer, Marsal Sanches, Jair C Soares Jan 2023

Processing Speed – A Potential Candidate Cognitive Endophenotype For Bipolar Disorder, Mirona Letitia Dobri, Taya Prince, Alexandre Paim Diaz, Giovana B Zunta-Soares, Sudhakar Selvaraj, Rodrigo Machado-Vieira, Thomas D Meyer, Marsal Sanches, Jair C Soares

Faculty, Staff and Student Publications

BACKGROUND: Bipolar disorder (BD) is a chronic multifactorial disorder that presents with cognitive impairment as one of its main features, in patients as well as in their first-degree relatives. However, the profile of cognitive dysfunction in BD patients and their relatives is not yet well defined. Various neurocognitive deficits have been proposed as endophenotypes for BD. In the present study, we explored the susceptibility to neurocognitive deficits in BD patients and their siblings compared to healthy controls.

METHOD: A sample consisting of patients diagnosed with BD (

RESULTS: Compared to healthy controls, BD patients and their unaffected siblings showed deficits …


Non-Canonical Pathways In The Pathophysiology And Therapeutics Of Bipolar Disorder, Rodrigo Machado-Vieira, Alan C Courtes, Carlos A Zarate, Ioline D Henter, Husseini K Manji Jan 2023

Non-Canonical Pathways In The Pathophysiology And Therapeutics Of Bipolar Disorder, Rodrigo Machado-Vieira, Alan C Courtes, Carlos A Zarate, Ioline D Henter, Husseini K Manji

Faculty, Staff and Student Publications

Bipolar disorder (BD) is characterized by extreme mood swings ranging from manic/hypomanic to depressive episodes. The severity, duration, and frequency of these episodes can vary widely between individuals, significantly impacting quality of life. Individuals with BD spend almost half their lives experiencing mood symptoms, especially depression, as well as associated clinical dimensions such as anhedonia, fatigue, suicidality, anxiety, and neurovegetative symptoms. Persistent mood symptoms have been associated with premature mortality, accelerated aging, and elevated prevalence of treatment-resistant depression. Recent efforts have expanded our understanding of the neurobiology of BD and the downstream targets that may help track clinical outcomes and …