Medicine and Health Sciences Commons^™

Microenvironmental Ammonia Enhances T Cell Exhaustion In Colorectal Cancer, Hannah N Bell, Amanda K Huber, Rashi Singhal, Navyateja Korimerla, Ryan J Rebernick, Roshan Kumar, Marwa O El-Derany, Peter Sajjakulnukit, Nupur K Das, Samuel A Kerk, Sumeet Solanki, Jadyn G James, Donghwan Kim, Li Zhang, Brandon Chen, Rohit Mehra, Timothy L Frankel, Balázs Győrffy, Eric R Fearon, Marina Pasca Di Magliano, Frank J Gonzalez, Ruma Banerjee, Daniel R Wahl, Costas A Lyssiotis, Michael Green, Yatrik M Shah

Faculty, Staff and Student Publications

Effective therapies are lacking for patients with advanced colorectal cancer (CRC). The CRC tumor microenvironment has elevated metabolic waste products due to altered metabolism and proximity to the microbiota. The role of metabolite waste in tumor development, progression, and treatment resistance is unclear. We generated an autochthonous metastatic mouse model of CRC and used unbiased multi-omic analyses to reveal a robust accumulation of tumoral ammonia. The high ammonia levels induce T cell metabolic reprogramming, increase exhaustion, and decrease proliferation. CRC patients have increased serum ammonia, and the ammonia-related gene signature correlates with altered T cell response, adverse patient outcomes, and …

Revision Of The Melanocytic Pathology Assessment Tool And Hierarchy For Diagnosis Classification Schema For Melanocytic Lesions: A Consensus Statement, Raymond L Barnhill, David E Elder, Michael W Piepkorn, Stevan R Knezevich, Lisa M Reisch, Megan M Eguchi, Boris C Bastian, Willeke Blokx, Marcus Bosenberg, Klaus J Busam, Richard Carr, Alistair Cochran, Martin G Cook, Lyn M Duncan, Rosalie Elenitsas, Arnaud De La Fouchardière, Pedram Gerami, Iva Johansson, Jennifer Ko, Gilles Landman, Alexander J Lazar, Lori Lowe, Daniela Massi, Jane Messina, Daniela Mihic-Probst, Douglas C Parker, Birgitta Schmidt, Christopher R Shea, Richard A Scolyer, Michael Tetzlaff, Xiaowei Xu, Iwei Yeh, Artur Zembowicz, Joann G Elmore

Faculty, Staff and Student Publications

Importance: A standardized pathology classification system for melanocytic lesions is needed to aid both pathologists and clinicians in cataloging currently existing diverse terminologies and in the diagnosis and treatment of patients. The Melanocytic Pathology Assessment Tool and Hierarchy for Diagnosis (MPATH-Dx) has been developed for this purpose.

Objective: To revise the MPATH-Dx version 1.0 classification tool, using feedback from dermatopathologists participating in the National Institutes of Health-funded Reducing Errors in Melanocytic Interpretations (REMI) Study and from members of the International Melanoma Pathology Study Group (IMPSG).

Evidence review: Practicing dermatopathologists recruited from 40 US states participated in the 2-year REMI study …

Distribution Pattern Of Antibiotic Resistance Genes In Escherichia Coli Isolated From Colibacillosis Cases In Broiler Farms Of Egypt, Mona A A Abdel-Rahman, Engy A Hamed, May F Abdelaty, Hend K Sorour, Heba Badr, Wafaa M Hassan, Azhar G Shalaby, Ahmed Abd-Elhalem Mohamed, Mohamed A Soliman, Heba Roshdy

Faculty, Staff and Student Publications

BACKGROUND AND AIM: Multidrug resistance (MDR) of

MATERIALS AND METHODS: Samples from 938 broiler farms were bacteriologically examined for

RESULTS:

CONCLUSION: The study showed a high prevalence of

Psychotic Symptom, Mood, And Cognition-Associated Multimodal Mri Reveal Shared Links To The Salience Network Within The Psychosis Spectrum Disorders, Chuang Liang, Godfrey Pearlson, Juan Bustillo, Peter Kochunov, Jessica A Turner, Xuyun Wen, Rongtao Jiang, Zening Fu, Xiao Zhang, Kaicheng Li, Xijia Xu, Daoqiang Zhang, Shile Qi, Vince D Calhoun

Faculty, Staff and Student Publications

Schizophrenia (SZ), schizoaffective disorder (SAD), and psychotic bipolar disorder share substantial overlap in clinical phenotypes, associated brain abnormalities and risk genes, making reliable diagnosis among the three illness challenging, especially in the absence of distinguishing biomarkers. This investigation aims to identify multimodal brain networks related to psychotic symptom, mood, and cognition through reference-guided fusion to discriminate among SZ, SAD, and BP. Psychotic symptom, mood, and cognition were used as references to supervise functional and structural magnetic resonance imaging (MRI) fusion to identify multimodal brain networks for SZ, SAD, and BP individually. These features were then used to assess the ability …

Vessel Patency And Associated Factors Of Drug-Coated Balloon For Femoropopliteal Lesion, Yoshimitsu Soga, Mitsuyoshi Takahara, Osamu Iida, Yusuke Tomoi, Daizo Kawasaki, Akiko Tanaka, Yasutaka Yamauchi, Kazuki Tobita, Amane Kozuki, Masahiko Fujihara, Kenji Ando

Faculty, Staff and Student Publications

Background Although clinical trials have reported favorable outcomes after drug-coated balloon (DCB) therapy for femoropopliteal lesions, their real-world performance and predictors have not been well evaluated. This study aimed to elucidate 1-year freedom from restenosis and to explore the associated factors after a DCB for femoropopliteal lesions in clinical settings. Methods and Results This multicenter, prospective cohort registered 3165 de novo or restenotic femoropopliteallesions (mean lesion length, 13.5±9.3 cm; chronic total occlusion, 25.9%; severe calcification, 14.6%) that underwent successful DCB (Lutonix [24.2%] and IN.PACT Admiral [75.8%]) treatment between March 2018 and December 2019. Patency was assessed at 12±2 months. The …

Inhibiting Androgen Receptor Splice Variants With Cysteine-Selective Irreversible Covalent Inhibitors To Treat Prostate Cancer, Thirumagal Thiyagarajan, Suriyan Ponnusamy, Dong-Jin Hwang, Yali He, Sarah Asemota, Kirsten L Young, Daniel L Johnson, Vera Bocharova, Weidong Zhou, Abhinav K Jain, Emanuel F Petricoin, Zheng Yin, Lawrence M Pfeffer, Duane D Miller, Ramesh Narayanan

Faculty, Staff and Student Publications

Androgen receptor (AR) and its splice variants (AR-SVs) promote prostate cancer (PCa) growth by orchestrating transcriptional reprogramming. Mechanisms by which the low complexity and intrinsically disordered primary transactivation domain (AF-1) of AR and AR-SVs regulate transcriptional programming in PCa remains poorly defined. Using omics, live and fixed fluorescent microscopy of cells, and purified AF-1 and AR-V7 recombinant proteins we show here that AF-1 and the AR-V7 splice variant form molecular condensates by liquid-liquid phase separation (LLPS) that exhibit disorder characteristics such as rapid intracellular mobility, coactivator interaction, and euchromatin induction. The LLPS and other disorder characteristics were reversed by a …

Radiofrequency Ablation Remodels The Tumor Microenvironment And Promotes Neutrophil-Mediated Abscopal Immunomodulation In Pancreatic Cancer, Erika Y Faraoni, Baylee J O'Brien, Lincoln N Strickland, Baron K Osborn, Victoria Mota, Jarod Chaney, Constance Lynn Atkins, Putao Cen, Julie Rowe, Jessica Cardenas, Kyle L Poulsen, Curtis J Wray, Nirav C Thosani, Jennifer M Bailey-Lundberg

Faculty, Staff and Student Publications

Pancreatic ductal adenocarcinoma (PDAC) presents a 5-year overall survival rate of 11%, despite efforts to improve clinical outcomes in the past two decades. Therapeutic resistance is a hallmark of this disease, due to its dense and suppressive tumor microenvironment (TME). Endoscopic ultrasound-guided radiofrequency ablation (EUS-RFA) is a promising local ablative and potential immunomodulatory therapy for PDAC. In this study, we performed RFA in a preclinical tumor-bearing KrasG12D; Trp53R172H/+; Pdx1:Cre (KPC) syngeneic model, analyzed local and abscopal affects after RFA and compared our findings with resected PDAC specimens. We found that RFA reduced PDAC tumor progression in vivo and promoted strong …

Subtype And Site Specific-Induced Metabolic Vulnerabilities In Prostate Cancer, Federica Mossa, Daniele Robesti, Ramachandran Sumankalai, Eva Corey, Mark Titus, Yuqi Kang, Jianhua Zhang, Alberto Briganti, Francesco Montorsi, Christopher P Vellano, Joseph R Marszalek, Daniel E Frigo, Christopher J Logothetis, Taranjit S Gujral, Eleonora Dondossola

Faculty, Staff and Student Publications

Aberrant metabolic functions play a crucial role in prostate cancer progression and lethality. Currently, limited knowledge is available on subtype-specific metabolic features and their implications for treatment. We therefore investigated the metabolic determinants of the two major subtypes of castration-resistant prostate cancer [androgen receptor-expressing prostate cancer (ARPC) and aggressive variant prostate cancer (AVPC)]. Transcriptomic analyses revealed enrichment of gene sets involved in oxidative phosphorylation (OXPHOS) in ARPC tumor samples compared with AVPC. Unbiased screening of metabolic signaling pathways in patient-derived xenograft models by proteomic analyses further supported an enrichment of OXPHOS in ARPC compared with AVPC, and a skewing toward …

Robotically Assisted Mitral Valve Repair—Port-Only Totally Endoscopic Approach, Kellen J. Round, Colin C. Yost, Jake L. Rosen, Jenna L. Mandel, Meagan Wu, Luke C. Olson, Jordan E. Goldhammer, T. Sloane Guy

Department of Surgery Faculty Papers

Robotic mitral valve repair (MVR) is an emerging option to treat degenerative valve disease. Compared to open thoracotomy, robotic mitral valve surgery has been shown to afford decreased postoperative length of stay with comparable rates of mortality and morbidity. Among the variety of techniques for robotic MVR, the totally endoscopic approach remains the least invasive method to date. In this report, we describe our technique for totally endoscopic robotically-assisted MVR. In particular, we seek to highlight the use of several unique techniques in MVR. Percutaneous cannulation with use of the endoballoon is employed for cardiopulmonary bypass (CPB), thus avoiding traditional …

Longitudinal Developmental Outcomes Of Infants And Toddlers With Traumatic Brain Injury, Heather T Keenan, Amy Clark, Rich Holubkov, Linda Ewing-Cobbs

Faculty, Staff and Student Publications

IMPORTANCE: Among children, infants and toddlers have some of the highest rates of traumatic brain injury (TBI), but longitudinal information on their developmental outcomes to guide postinjury surveillance is sparse.

OBJECTIVE: To evaluate infants' and toddlers' development over 3 years following TBI compared with those with orthopedic injury (OI).

DESIGN, SETTING, AND PARTICIPANTS: A longitudinal observational cohort study was conducted at 2 level 1 pediatric trauma centers from January 20, 2013, to September 30, 2015; data analysis was performed from May 12 to October 20, 2021. Participants included children injured when younger than 31 months with TBI or OI who …

Evaluation Of Proton Therapy Reirradiation For Patients With Recurrent Head And Neck Squamous Cell Carcinoma, Anna Lee, Robbie Woods, Amgad Mahfouz, Sarin Kitpanit, Olivia Cartano, Nader Mohamed, Irini Youssef, Kathryn Marqueen, Kevin Sine, Dennis Mah, Brian Neal, Kaveh Zakeri, Jung J Kang, Nadeem Riaz, Yao Yu, Sean M Mcbride, Linda D Chen, C Jillian Tsai, Daphna Y Gelblum, Robert H Press, Loren S Michel, Eric J Sherman, David Pfister, Lara A Dunn, Alan L Ho, James Fetten, Richard J Wong, Jay O Boyle, Bhuvanesh Singh, Jennifer R Cracchiolo, Ian Ganly, Marc A Cohen, Nancy Y Lee

Faculty, Staff and Student Publications

Importance: Use of proton therapy reirradiation (PT-ReRT) for head and neck cancer is increasing; however, reports are heterogenous and outcomes can be difficult to interpret.

Objective: To evaluate outcomes and toxic effects following PT-ReRT in a uniform and consecutive cohort of patients with head and neck squamous cell carcinoma.

Design, setting, and participants: This retrospective cohort study included patients with recurrent primary head and neck squamous cell carcinoma who were treated with PT-ReRT from January 1, 2013, to December 31, 2020, at a single institution. Patient, clinical, and treatment characteristics were obtained, and multidisciplinary review was performed to record and …

Antisense Oligonucleotide Therapy Rescues Disturbed Brain Rhythms And Sleep In Juvenile And Adult Mouse Models Of Angelman Syndrome, Dongwon Lee, Wu Chen, Heet Naresh Kaku, Xinming Zhuo, Eugene S Chao, Armand Soriano, Allen Kuncheria, Stephanie Flores, Joo Hyun Kim, Armando Rivera, Frank Rigo, Paymaan Jafar-Nejad, Arthur L Beaudet, Matthew S Caudill, Mingshan Xue

Faculty, Staff and Students Publications

UBE3A encodes ubiquitin protein ligase E3A, and in neurons its expression from the paternal allele is repressed by the UBE3A antisense transcript (UBE3A-ATS). This leaves neurons susceptible to loss-of-function of maternal UBE3A. Indeed, Angelman syndrome, a severe neurodevelopmental disorder, is caused by maternal UBE3A deficiency. A promising therapeutic approach to treating Angelman syndrome is to reactivate the intact paternal UBE3A by suppressing UBE3A-ATS. Prior studies show that many neurological phenotypes of maternal Ube3a knockout mice can only be rescued by reinstating Ube3a expression in early development, indicating a restricted therapeutic window for Angelman syndrome. Here, we …

Mitochondrial Dysfunction Reactivates Α-Fetoprotein Expression That Drives Copper-Dependent Immunosuppression In Mitochondrial Disease Models, Kimberly A Jett, Zakery N Baker, Amzad Hossain, Aren Boulet, Paul A Cobine, Sagnika Ghosh, Philip Ng, Orhan Yilmaz, Kris Barreto, John Decoteau, Karen Mochoruk, George N Ioannou, Christopher Savard, Sai Yuan, Osama Hmh Abdalla, Christopher Lowden, Byung-Eun Kim, Hai-Ying Mary Cheng, Brendan J Battersby, Vishal M Gohil, Scot C Leary

Faculty, Staff and Students Publications

Signaling circuits crucial to systemic physiology are widespread, yet uncovering their molecular underpinnings remains a barrier to understanding the etiology of many metabolic disorders. Here, we identified a copper-linked signaling circuit activated by disruption of mitochondrial function in the murine liver or heart that resulted in atrophy of the spleen and thymus and caused a peripheral white blood cell deficiency. We demonstrated that the leukopenia was caused by α-fetoprotein, which required copper and the cell surface receptor CCR5 to promote white blood cell death. We further showed that α-fetoprotein expression was upregulated in several cell types upon inhibition of oxidative …

Effect Of A Muc5ac Antibody (Npc-1c) Administered With Second-Line Gemcitabine And Nab-Paclitaxel On The Survival Of Patients With Advanced Pancreatic Ductal Adenocarcinoma: A Randomized Clinical Trial, Brandon M Huffman, Andrea Wang-Gillam, Et Al.

2020-Current year OA Pubs

IMPORTANCE: Treatment options are limited for patients with advanced pancreatic ductal adenocarcinoma (PDAC) beyond first-line 5-fluorouracil, leucovorin, irinotecan, and oxaliplatin (FOLFIRINOX), with such individuals commonly being treated with gemcitabine and nab-paclitaxel.

OBJECTIVE: To determine whether NPC-1C, an antibody directed against MUC5AC, might increase the efficacy of second-line gemcitabine and nab-paclitaxel in patients with advanced PDAC.

DESIGN, SETTING, AND PARTICIPANTS: This multicenter, randomized phase II clinical trial enrolled patients with advanced PDAC between April 2014 and March 2017 whose disease had progressed on first-line FOLFIRINOX. Eligible patients had tumors with at least 20 MUC5AC staining by centralized immunohistochemistry review. Statistical analysis …

Arginine Methylation Of The Pgc-1Α C-Terminus Is Temperature-Dependent, Meryl Mendoza, Mariel Mendoza, Tiffany Lubrino, Sidney Briski, Immaculeta Osuji, Janielle Cuala, Brendan Ly, Ivan Ocegueda, Harvey Peralta, Benjamin A. Garcia, Cecilia I. Zurita-Lopez

2020-Current year OA Pubs

We set out to determine whether the C-terminus (amino acids 481-798) of peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC-1α, UniProt Q9UBK2), a regulatory metabolic protein involved in mitochondrial biogenesis, and respiration, is an arginine methyltransferase substrate. Arginine methylation by protein arginine methyltransferases (PRMTs) alters protein function and thus contributes to various cellular processes. In addition to confirming methylation of the C-terminus by PRMT1 as described in the literature, we have identified methylation by another member of the PRMT family, PRMT7. We performed

Association Of State Insurance Mandates For Fertility Treatment With Multiple Embryo Transfer After Preimplantation Genetic Testing For Aneuploidy, Bronwyn S Bedrick, Katelin B Nickel, Joan K Riley, Tarun Jain, Emily S Jungheim

2020-Current year OA Pubs

IMPORTANCE: Multiple gestation is one of the biggest risks after in vitro fertilization (IVF), largely due to multiple embryo transfer (MET). Single embryo transfer (SET) uptake has increased over time and has been attributed to various factors, such as mandated insurance coverage for IVF and preimplantation genetic testing for aneuploidy (PGT-A).

OBJECTIVE: To investigate whether mandates for IVF insurance coverage are associated with decreased use of MET after PGT-A.

DESIGN, SETTING, AND PARTICIPANTS: This cohort study was conducted using data on embryo transfers reported to the Society for Assisted Reproductive Technology between 2014 and 2016. Data were analyzed from January …

Advancement In Human Face Prediction Using Dna, Aamer Alshehhi, Aliya Almarzooqi, Khadija Alhammadi, Naoufel Werghi, Guan Kwang Tay, Habiba Alsafar

Research outputs 2022 to 2026

The rapid improvements in identifying the genetic factors contributing to facial morphology have enabled the early identification of craniofacial syndromes. Similarly, this technology can be vital in forensic cases involving human identification from biological traces or human remains, especially when reference samples are not available in the deoxyribose nucleic acid (DNA) database. This review summarizes the currently used methods for predicting human phenotypes such as age, ancestry, pigmentation, and facial features based on genetic variations. To identify the facial features affected by DNA, various two-dimensional (2D)- and three-dimensional (3D)-scanning techniques and analysis tools are reviewed. A comparison between the scanning …

Provider Beliefs In Effectiveness And Recommendations For Primary Hpv Testing In 3 Health-Care Systems, Gina R Kruse, Jacquelyn M Lykken, Eric J Kim, Jennifer S Haas, Robin T Higashi, Steven J Atlas, Anne Marie Mccarthy, Jasmin A Tiro, Michelle I Silver, Celette S Skinner, Aruna Kamineni

2020-Current year OA Pubs

In 2018, the US Preventive Services Task Force endorsed primary human papillomavirus testing (pHPV) for cervical cancer screening. We aimed to describe providers' beliefs about pHPV testing effectiveness and which screening approach they regularly recommend. We invited providers who performed 10 or more cervical cancer screens in 2019 in 3 healthcare systems that had not adopted pHPV testing: Kaiser Permanente Washington, Mass General Brigham, and Parkland Health; 53.7% (501/933) completed the survey between October and December 2020. Response distributions varied across modalities (P < .001), with cytology alone or cotesting being more often viewed as somewhat or very effective for 30- to 65-year-olds compared with pHPV (cytology alone 94.1%, cotesting 96.1%, pHPV 66.0%). In 21- to 29-year-olds, the pattern was similar (cytology alone 92.2%, 64.7% cotesting, 50.8% pHPV). Most providers were either incorrect or unsure of the guideline-recommended screening interval for pHPV. Educational efforts are needed about the relative effectiveness and recommended use of pHPV to promote guideline-concordant care.

Follistatin Regulates The Specification Of The Apical Cochlea Responsible For Low-Frequency Hearing In Mammals, Hei Yeun Koo, Min-A Kim, Hyehyun Min, Jae Yeon Hwang, Meenakshi Prajapati-Dinubila, Kwan Soo Kim, Martin M Matzuk, Juw Won Park, Angelika Doetzlhofer, Un-Kyung Kim, Jinwoong Bok

Faculty, Staff and Students Publications

The cochlea's ability to discriminate sound frequencies is facilitated by a special topography along its longitudinal axis known as tonotopy. Auditory hair cells located at the base of the cochlea respond to high-frequency sounds, whereas hair cells at the apex respond to lower frequencies. Gradual changes in morphological and physiological features along the length of the cochlea determine each region's frequency selectivity, but it remains unclear how tonotopy is established during cochlear development. Recently, sonic hedgehog (SHH) was proposed to initiate the establishment of tonotopy by conferring regional identity to the primordial cochlea. Here, using mouse genetics, we provide in …

A Spontaneous Nonhuman Primate Model Of Myopic Foveoschisis, Tzu-Ni Sin, Sangbae Kim, Yumei Li, Jun Wang, Rui Chen, Sook Hyun Chung, Soohyun Kim, M Isabel Casanova, Sangwan Park, Zeljka Smit-Mcbride, Ning Sun, Ori Pomerantz, Jeffrey A Roberts, Bin Guan, Robert B Hufnagel, Ala Moshiri, Sara M Thomasy, Paul A Sieving, Glenn Yiu

Faculty, Staff and Students Publications

Purpose: Foveoschisis involves the pathologic splitting of retinal layers at the fovea, which may occur congenitally in X-linked retinoschisis (XLRS) or as an acquired complication of myopia. XLRS is attributed to functional loss of the retinal adhesion protein retinoschisin 1 (RS1), but the pathophysiology of myopic foveoschisis is unclear due to the lack of animal models. Here, we characterized a novel nonhuman primate model of myopic foveoschisis through clinical examination and multimodal imaging followed by morphologic, cellular, and transcriptional profiling of retinal tissues and genetic analysis.

Methods: We identified a rhesus macaque with behavioral and anatomic features of myopic foveoschisis, …

Large Variations In The Prices Of Urologic Procedures At Academic Medical Centers 1 Year After Implementation Of The Price Transparency Final Rule, Zeynep G Gul, Danielle R Sharbaugh, Cailey J Guercio, Daniel L Pelzman, Cameron A Jones, Emily C Hacker, Vivian I Anyaeche, Levi Bowers, Ashti M Shah, Michael G Stencel, Jonathan G Yabes, Bruce L Jacobs, Benjamin J Davies

2020-Current year OA Pubs

IMPORTANCE: Patients with urologic diseases often experience financial toxicity, defined as high levels of financial burden and concern, after receiving care. The Price Transparency Final Rule, which requires hospitals to disclose both the commercial and cash prices for at least 300 services, was implemented to facilitate price shopping, decrease price dispersion, and lower health care costs.

OBJECTIVE: To evaluate compliance with the Price Transparency Final Rule and to quantify variations in the price of urologic procedures among academic hospitals and by insurance class.

DESIGN, SETTING, AND PARTICIPANTS: This was a cross-sectional study that determined the prices of 5 common urologic …

Vista Targeting Of T-Cell Quiescence And Myeloid Suppression Overcomes Adaptive Resistance, Evelien Schaafsma, Walburga Croteau, Mohamed Eltanbouly, Elizabeth C Nowak, Nicole C Smits, Jie Deng, Aurelien Sarde, Cecilia A Webber, Dina Rabadi, Chao Cheng, Randolph Noelle, J Louise Lines

Faculty, Staff and Students Publications

VISTA is a premier target for cancer treatment due to its broad expression in many cancer types and enhanced expression upon development of adaptive immune checkpoint resistance. In the CT26 colorectal cancer model, monotherapy of small tumors with anti-VISTA resulted in slowed tumor growth. In a combination therapy setting, large CT26 tumors showed complete adaptive resistance to anti-PD-1/CTLA-4, but inclusion of anti-VISTA led to rejection of half the tumors. Mechanisms of enhanced anti-tumor immunity were investigated using scRNA-seq, multiplex image analysis and flow cytometry of the tumor immune infiltrate. In both treatment models, anti-VISTA upregulated stimulated antigen-presentation pathways and reduced …

Are Sub-Saharan African National Food And Agriculture Policies Nutrition-Sensitive? A Case Study Of Ethiopia, Ghana, Malawi, Nigeria, And South Africa, Roshaany Asirvatham

Health Studies Publications

Background

In sub-Saharan Africa (SSA), malnutrition coupled with rising rates of undernutrition and the burden of overweight/obesity remains one of the most significant public health challenges facing the region. Nutrition-sensitive agriculture can play an important role in reducing malnutrition by addressing the underlying causes of nutrition outcomes. Therefore, we aim to assess the nutrition-sensitivity of food and agriculture policies in SSA and to provide recommendations for identified policy challenges in implementing nutrition-sensitive agriculture initiatives.

Methods

We assessed past and current national policies relevant to agriculture and nutrition from Ethiopia, Ghana, Malawi, Nigeria, and South Africa. Thirty policies and strategies were …

Epidemiological/Disease And Economic Burdens Of Cervical Cancer In 2010–2014: Are Younger Women At Risk?, Chuhao Xi, Jay J. Shen, Betty Burston, Soumya Upadhyay, Shoujun Zhou

Healthcare Administration and Policy Faculty Research

Objective: Cervical cancer is an important factor threatening women’s health in China. This study examined the epidemiological and economic burden of cervical cancer among the medically insured population, which could provide data support for government departments to formulate policies. Methods: All new cases of cervical cancer under the Urban Employee Basic Medical Insurance (UEBMI) plan in a provincial capital city in eastern China from 2010 to 2014 were collected. The Cox proportional hazard model was used to analyze the factors affecting the survival rates for cervical cancer. Outpatient and hospitalization expenses were used to assess the direct economic burden, and …

Investigating The Role Of Vasopressin Receptor 1a Expressing Neurons In Mouse Dorsal Raphe, Tirth Nimishbhai Patel

Theses and Dissertations

Human social interactions heavily impact our physical and mental wellbeing. Arginine-vasopressin (Avp) and serotonin have both been implicated in modulation of social behaviors ranging from affiliation to aggression. In male mice, Avp neurons in the bed nucleus of stria terminalis (BNST) show increased activity during prosocial behavior. BNST sends Avp afferents to the dorsal raphe (DR) in the midbrain, a home to a large portion of serotonin neurons in the mouse brain. Previous data suggests that DR is activated during male prosocial behavior with a female stimulus, and Avp indirectly excites serotonin neurons. We hypothesized that DR contains a population …

Repurposing Ms Immunotherapies For Cidp And Other Autoimmune Neuropathies: Unfulfilled Promise Or Efficient Strategy?, Felix Kohle, Marinos Dalakas, Helmar C Lehmann

Department of Neurology Faculty Papers

Despite advances in the treatment of chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) and other common autoimmune neuropathies (AN), still-many patients with these diseases do not respond satisfactorily to the available treatments. Repurposing of disease-modifying therapies (DMTs) from other autoimmune conditions, particularly multiple sclerosis (MS) and neuromyelitis optica spectrum disorders (NMOSD), is a promising strategy that may accelerate the establishment of novel treatment choices for AN. This approach appears attractive due to homologies in the pathogenesis of these diseases and the extensive post-marketing experience that has been gathered from treating MS and NMOSD patients. The idea is also strengthened by a number …

The Impact Of Adolescent Maternal Age On Neonatal Outcomes And Neurodevelopment, Sarah Hanna

Honors Scholar Theses

To explore the association between maternal age and obstetric and neonatal outcomes with a focus on adolescent women between the age of 18 to 21 years. Secondary Analysis of RO1 cohort study. Maternity departments of six hospitals in Connecticut - Hartford Hospital, UConn John Dempsey Hospital, Saint Francis Hospital, Manchester Memorial Hospital, William W. Backus Hospital, or other - with relation to The University of Connecticut or Connecticut Children’s Medical Center. The primary outcomes were maternal and neonatal outcomes measured in addition to neonatal neurodevelopment. Neonates born to adolescent mothers exhibited lower birth weight (p=0.004). Based on the Bayley Scales …

Medical Training Of Seafarers: International Maritime Health Foundation (Imhf) Expert Panel Consensus Statement, Nebojša Nikolić, Jon Magnus Haga, Jens Tülsner, Per Otto Årland, Alf Magne Horneland, Bill Kavanagh, Klaus Seidenstucker, Spike Briggs, Inger Lund-Kordahl, Cecilia Simolin Pernilla

Articles

Background: Medical emergencies and on-going medical conditions on board may seriously impair seafarers’ health and safety, and also negatively impact on future work prospects for seafarers. When a seafarer gets ill or injured on a ship, medical treatment often relies on the competences on his colleagues on board. The aim of this project was to establish a consensus-based minimum standard for medical education for seafarers, in order to ensure competency for adequate management of ill-health on board.

Materials and methods: International Maritime Health Foundation (IMHF) conducted a workshop on medical training of seafarers. A research-based approach to gain consensus on …

The Phytophthora Sojae Nuclear Effector Psavh110 Targets A Host Transcriptional Complex To Modulate Plant Immunity, Xufang Qiu, Liang Kong, Han Chen, Yachun Lin, Siqun Tu, Lei Wang, Zhiyuan Chen, Mengzhu Zeng, Junhua Xiao, Peiguo Yuan, Min Qiu, Yan Wang, Wenwu Ye, Kaixuan Duan, Suomeng Dong, Yuanchao Wang

Faculty, Staff and Student Publications

Plants have evolved sophisticated immune networks to restrict pathogen colonization. In response, pathogens deploy numerous virulent effectors to circumvent plant immune responses. However, the molecular mechanisms by which pathogen-derived effectors suppress plant defenses remain elusive. Here, we report that the nucleus-localized RxLR effector PsAvh110 from the pathogen Phytophthora sojae, causing soybean (Glycine max) stem and root rot, modulates the activity of a transcriptional complex to suppress plant immunity. Soybean like-heterochromatin protein 1-2 (GmLHP1-2) and plant homeodomain finger protein 6 (GmPHD6) form a transcriptional complex with transcriptional activity that positively regulates plant immunity against Phytophthora infection. To suppress plant immunity, the …

Fn14-Directed Dart Nanoparticles Selectively Target Neoplastic Cells In Preclinical Models Of Triple-Negative Breast Cancer Brain Metastasis, Christine P Carney, Anshika Kapur, Pavlos Anastasiadis, Rodney M Ritzel, Chixiang Chen, Graeme F Woodworth, Jeffrey A Winkles, Anthony J Kim

Faculty, Staff and Student Publications

Triple-negative breast cancer (TNBC) patients with brain metastasis (BM) face dismal prognosis due to the limited therapeutic efficacy of the currently available treatment options. We previously demonstrated that paclitaxel-loaded PLGA−PEG nanoparticles (NPs) directed to the Fn14 receptor, termed “DARTs”, are more efficacious than Abraxane—an FDA-approved paclitaxel nanoformulation—following intravenous delivery in a mouse model of TNBC BM. However, the precise basis for this difference was not investigated. Here, we further examine the utility of the DART drug delivery platform in complementary xenograft and syngeneic TNBC BM models. First, we demonstrated that, in comparison to nontargeted NPs, DART NPs exhibit preferential association …