Medical Specialties Commons^™

Improved Cognitive Outcomes In Patients With Relapsing-Remitting Multiple Sclerosis Treated With Daclizumab Beta: Results From The Decide Study., Ralph Hb Benedict, Stanley Cohan, Sharon G Lynch, Katherine Riester, Ping Wang, Wanda Castro-Borrero, Jacob Elkins, Guido Sabatella

Articles, Abstracts, and Reports

BACKGROUND: Cognitive impairment is common in multiple sclerosis (MS), with cognitive processing speed being the most frequently affected domain.

OBJECTIVE: Examine the effects of daclizumab beta versus intramuscular (IM) interferon (IFN) beta-1a on cognitive processing speed as assessed by Symbol Digit Modalities Test (SDMT).

METHODS: In DECIDE, patients with relapsing-remitting multiple sclerosis (RRMS) (age: 18-55 years; Expanded Disability Status Scale (EDSS) score 0-5.0) were randomized to daclizumab beta ( n = 919) or IM IFN beta-1a ( n = 922) for 96-144 weeks. SDMT was administered at baseline and at 24-week intervals.

RESULTS: At week 96, significantly greater mean improvement …

Loss Of Inter-Cellular Cooperation By Complete Epithelial-Mesenchymal Transition Supports Favorable Outcomes In Basal Breast Cancer Patients., Anne Grosse-Wilde, Rolf E Kuestner, Stephanie M Skelton, Ellie Macintosh, Aymeric Fouquier D'Hérouël, Gökhan Ertaylan, Antonio Del Sol, Alexander Skupin, Sui Huang

Articles, Abstracts, and Reports

According to the sequential metastasis model, aggressive mesenchymal (M) metastasis-initiating cells (MICs) are generated by an epithelial-mesenchymal transition (EMT) which eventually is reversed by a mesenchymal-epithelial transition (MET) and outgrowth of life-threatening epithelial (E) macrometastases. Paradoxically, in breast cancer M signatures are linked with more favorable outcomes than E signatures, and M cells are often dispensable for metastasis in mouse models. Here we present evidence at the cellular and patient level for the cooperation metastasis model, according to which E cells are MICs, while M cells merely support E cell persistence through cooperation. We tracked the fates of co-cultured E …

Macrophage-Derived Il-1Β/Nf-Κb Signaling Mediates Parenteral Nutrition-Associated Cholestasis., Karim C El Kasmi, Padade M Vue, Aimee L Anderson, Michael W Devereaux, Swati Ghosh, Natarajan Balasubramaniyan, Sophie A Fillon, Carola Dahrenmoeller, Ayed Allawzi, Crystal Woods, Sarah Mckenna, Clyde J Wright, Linda Johnson, Angelo D'Alessandro, Julie A Reisz, Eva Nozik-Grayck, Frederick J Suchy, Ronald J Sokol

Articles, Abstracts, and Reports

In infants intolerant of enteral feeding because of intestinal disease, parenteral nutrition may be associated with cholestasis, which can progress to end-stage liver disease. Here we show the function of hepatic macrophages and phytosterols in parenteral nutrition-associated cholestasis (PNAC) pathogenesis using a mouse model that recapitulates the human pathophysiology and combines intestinal injury with parenteral nutrition. We combine genetic, molecular, and pharmacological approaches to identify an essential function of hepatic macrophages and IL-1β in PNAC. Pharmacological antagonism of IL-1 signaling or genetic deficiency in CCR2, caspase-1 and caspase-11, or IL-1 receptor (which binds both IL-1α and IL-1β) prevents PNAC in …

Coordinated Responses To Individual Tumor Antigens By Igg Antibody And Cd8+ T Cells Following Cancer Vaccination., Tyler W Hulett, Shawn M. Jensen, Phillip A Wilmarth, Ashok P Reddy, Carmen Ballesteros-Merino, Michael E Afentoulis, Christopher Dubay, Larry L David, Bernard A Fox

Articles, Abstracts, and Reports

BACKGROUND: One of today's greatest hurdles for cancer immunotherapy is the absence of information regarding which tumor antigens are already recognized by patients receiving immunotherapies, and whether those therapies then boost or generate an immune response against tumor proteins. For CD8+ T cells in particular, patient-specific immune recognition and responses at the level of individual tumor antigens are rarely characterized. Because of this, some immunologists have turned to serum antibodies as an alternative measure of antigen-specific anti-tumor immunity. In this work, we sought to simultaneously interrogate serum IgG and CD8+ T cell recognition of individual tumor antigens to determine whether …

Driver Fusions And Their Implications In The Development And Treatment Of Human Cancers., Qingsong Gao, Wen-Wei Liang, Steven M Foltz, Gnanavel Mutharasu, Reyka G Jayasinghe, Song Cao, Wen-Wei Liao, Sheila M Reynolds, Matthew A Wyczalkowski, Lijun Yao, Lihua Yu, Sam Q Sun, Ken Chen, Alexander J Lazar, Ryan C Fields, Michael C Wendl, Brian A Van Tine, Ravi Vij, Feng Chen, Matti Nykter, Ilya Shmulevich, Li Ding

Articles, Abstracts, and Reports

Gene fusions represent an important class of somatic alterations in cancer. We systematically investigated fusions in 9,624 tumors across 33 cancer types using multiple fusion calling tools. We identified a total of 25,664 fusions, with a 63% validation rate. Integration of gene expression, copy number, and fusion annotation data revealed that fusions involving oncogenes tend to exhibit increased expression, whereas fusions involving tumor suppressors have the opposite effect. For fusions involving kinases, we found 1,275 with an intact kinase domain, the proportion of which varied significantly across cancer types. Our study suggests that fusions drive the development of 16.5% of …

Genomic And Molecular Landscape Of Dna Damage Repair Deficiency Across The Cancer Genome Atlas., Theo A Knijnenburg, Linghua Wang, Michael T Zimmermann, Nyasha Chambwe, Galen F Gao, Andrew D Cherniack, Huihui Fan, Hui Shen, Gregory P Way, Casey S Greene, Yuexin Liu, Rehan Akbani, Bin Feng, Lawrence A Donehower, Chase Miller, Yang Shen, Mostafa Karimi, Haoran Chen, Pora Kim, Peilin Jia, Eve Shinbrot, Shaojun Zhang, Jianfang Liu, Hai Hu, Matthew H Bailey, Christina Yau, Denise Wolf, Zhongming Zhao, John N Weinstein, Lei Li, Li Ding, Gordon B Mills, Peter W Laird, David A Wheeler, Ilya Shmulevich, Raymond J Monnat, Yonghong Xiao, Chen Wang

Articles, Abstracts, and Reports

DNA damage repair (DDR) pathways modulate cancer risk, progression, and therapeutic response. We systematically analyzed somatic alterations to provide a comprehensive view of DDR deficiency across 33 cancer types. Mutations with accompanying loss of heterozygosity were observed in over 1/3 of DDR genes, including TP53 and BRCA1/2. Other prevalent alterations included epigenetic silencing of the direct repair genes EXO5, MGMT, and ALKBH3 in ∼20% of samples. Homologous recombination deficiency (HRD) was present at varying frequency in many cancer types, most notably ovarian cancer. However, in contrast to ovarian cancer, HRD was associated with worse outcomes in several other cancers. Protein …

Systematic Analysis Of Splice-Site-Creating Mutations In Cancer., Reyka G Jayasinghe, Song Cao, Qingsong Gao, Michael C Wendl, Nam Sy Vo, Sheila M Reynolds, Yanyan Zhao, Héctor Climente-González, Shengjie Chai, Fang Wang, Rajees Varghese, Mo Huang, Wen-Wei Liang, Matthew A Wyczalkowski, Sohini Sengupta, Zhi Li, Samuel H Payne, David Fenyö, Jeffrey H Miner, Matthew J Walter, Benjamin Vincent, Eduardo Eyras, Ken Chen, Ilya Shmulevich, Feng Chen, Li Ding

Articles, Abstracts, and Reports

For the past decade, cancer genomic studies have focused on mutations leading to splice-site disruption, overlooking those having splice-creating potential. Here, we applied a bioinformatic tool, MiSplice, for the large-scale discovery of splice-site-creating mutations (SCMs) across 8,656 TCGA tumors. We report 1,964 originally mis-annotated mutations having clear evidence of creating alternative splice junctions. TP53 and GATA3 have 26 and 18 SCMs, respectively, and ATRX has 5 from lower-grade gliomas. Mutations in 11 genes, including PARP1, BRCA1, and BAP1, were experimentally validated for splice-site-creating function. Notably, we found that neoantigens induced by SCMs are likely several folds more immunogenic compared to …

Spatial Organization And Molecular Correlation Of Tumor-Infiltrating Lymphocytes Using Deep Learning On Pathology Images., Joel Saltz, Rajarsi Gupta, Le Hou, Tahsin Kurc, Pankaj Singh, Vu Nguyen, Dimitris Samaras, Kenneth R Shroyer, Tianhao Zhao, Rebecca Batiste, John Van Arnam, Ilya Shmulevich, Arvind U K Rao, Alexander J Lazar, Ashish Sharma, Vésteinn Thorsson

Articles, Abstracts, and Reports

Beyond sample curation and basic pathologic characterization, the digitized H&E-stained images of TCGA samples remain underutilized. To highlight this resource, we present mappings of tumor-infiltrating lymphocytes (TILs) based on H&E images from 13 TCGA tumor types. These TIL maps are derived through computational staining using a convolutional neural network trained to classify patches of images. Affinity propagation revealed local spatial structure in TIL patterns and correlation with overall survival. TIL map structural patterns were grouped using standard histopathological parameters. These patterns are enriched in particular T cell subpopulations derived from molecular measures. TIL densities and spatial structure were differentially enriched …

Clinical Outcomes Of Endovascular Thrombectomy In Tissue Plasminogen Activator Versus Non-Tissue Plasminogen Activator Patients At Primary Stroke Care Centers., Gregory Imbarrato, Joshua Bentley, Ajeet Gordhan

Articles, Abstracts, and Reports

Background: The effect of intravenous tissue plasminogen activator (IV tPA) administration before endovascular intervention as compared to without at thrombectomy-capable low-volume centers on procedural aspects and patient outcomes has not been investigated.

Methods: Retrospective chart review was performed in all consecutive large vessel cerebrovascular accident patients treated with endovascular therapy at two select rural primary stroke centers between 2011 and 2015. Patients' data regarding age, sex, and medical history, as well as thrombus location by catheter-based cerebral angiography, postprocedural reperfusion status, and clinical outcomes were reviewed. The primary outcome measure of the study was a comparison of modified Rankin scale …

Hospital-Based Physicians' Intubation Decisions And Associated Mental Models When Managing A Critically And Terminally Ill Older Patient., Shannon Haliko, Julie Downs, Deepika Mohan, Robert Arnold, Amber E Barnato

Articles, Abstracts, and Reports

BACKGROUND: Variation in the intensity of acute care treatment at the end of life is influenced more strongly by hospital and provider characteristics than patient preferences.

OBJECTIVE: We sought to describe physicians' mental models (i.e., thought processes) when encountering a simulated critically and terminally ill older patient, and to compare those models based on whether their treatment plan was patient preference-concordant or preference-discordant.

METHODS: Seventy-three hospital-based physicians from 3 academic medical centers engaged in a simulated patient encounter and completed a mental model interview while watching the video recording of their encounter. We used an "expert" model to code the …

Response By Zghaib Et Al To Letter Regarding Article, "Standard Ablation Versus Magnetic Resonance Imaging-Guided Ablation In The Treatment Of Ventricular Tachycardia"., Tarek Zghaib, Esra G Ipek, Rozann Hansford, Hiroshi Ashikaga, Ronald D Berger, Joseph E Marine, David D Spragg, Harikrishna Tandri, Stefan L Zimmerman, Henry Halperin, Scott Brancato, Hugh Calkins, Charles Henrikson, Saman Nazarian

Articles, Abstracts, and Reports

No abstract provided.

Blood Transfusion And Postoperative Infection In Spine Surgery: A Systematic Review., Christian Fisahn, Cameron Schmidt, Josh E Schroeder, Emiliano Vialle, Isador H Lieberman, Joseph R Dettori, Thomas A Schildhauer

Articles, Abstracts, and Reports

Study Design: Systematic review.

Objectives: Allogeneic blood transfusion-related immunomodulation may relatively suppress the immune system, heightening the risk of infection following spine surgery. This systematic review seeks to determine whether allogeneic blood transfusion increases the risk of postoperative infection and whether there are any factors that modify this association.

Methods: PubMed, Cochrane Central Register of Controlled Trials, and reference lists from included studies were searched from inception to April 20, 2017 to identify studies examining the risk of infection following allogeneic blood transfusion in adult patients receiving surgery for degenerative spine disease.

Results: Eleven retrospective cohort or case-control studies, involving …

Upper And Lower Gastrointestinal Endoscopic Findings In Hiv-Infected Patients In The Era Of Highly Active Antiretroviral Therapy., Russell Parvin, Sindhura Kolli, Jamil Shah, Manan Jhaveri, Madhavi Reddy

Articles, Abstracts, and Reports

Background: Endoscopic evaluation with biopsies are instrumental in the diagnosis and management of gastrointestinal (GI) disorders in the setting of human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS), especially in the era of highly active antiretroviral therapy (HAART).

Methods: A retrospective chart review of 304 HIV-positive and 199 HIV-negative patients who had undergone upper and/or lower endoscopy in an urban community hospital from the years 2012 - 2017 was performed. Inclusion criteria included men and women between the ages of 45 to 75 years, which had undergone colonoscopies between within 2012 - 2017 and had tested positive for HIV. …

Menopausal-Related Symptoms In Women One Year After Breast Cancer Surgery., Melissa Mazor, Kathryn Lee, Anand Dhruva, Janine K Cataldo, Steven M Paul, Michelle Melisko, Betty J Smoot, Jon D Levine, Charles Elboim, Yvette P Conley, Christine Miaskowksi

Articles, Abstracts, and Reports

CONTEXT: Approximately 60% to 100% of women with breast cancer experience at least one menopausal-related symptom. Little is known about associations between menopausal status and symptoms in women 12 months after breast cancer surgery.

OBJECTIVES: The purpose of this study was to evaluate for differences in occurrence, severity, and distress of symptoms between pre- and postmenopausal women 12 months after breast cancer surgery.

METHODS: Women with breast cancer (n = 327) completed the Menopausal Symptoms Scale, which evaluated the occurrence, severity, and distress of 46 common menopausal-related symptoms. Regression analyses were used to evaluate between-group differences in the seven symptoms …

Addressing The Targeting Range Of The Abilhand-56 In Relapsing-Remitting Multiple Sclerosis: A Mixed Methods Psychometric Study., Sophie Cleanthous, Sara Strzok, Farrah Pompilus, Stefan Cano, Patrick Marquis, Stanley Cohan, Myla D Goldman, Kiren Kresa-Reahl, Jennifer Petrillo, Carmen Castrillo-Viguera, Diego Cadavid, Shih-Yin Chen

Articles, Abstracts, and Reports

Background: ABILHAND, a manual ability patient-reported outcome instrument originally developed for stroke patients, has been used in multiple sclerosis clinical trials; however, psychometric analyses indicated the measure's limited measurement range and precision in higher-functioning multiple sclerosis patients.

Objective: The purpose of this study was to identify candidate items to expand the measurement range of the ABILHAND-56, thus improving its ability to detect differences in manual ability in higher-functioning multiple sclerosis patients.

Methods: A step-wise mixed methods design strategy was used, comprising two waves of patient interviews, a combination of qualitative (concept elicitation and cognitive debriefing) and quantitative (Rasch measurement theory) …

Development Of A Gait Module To Complement The 12-Item Multiple Sclerosis Walking Scale: A Mixed Methods Study., Sara Strzok, Sophie Cleanthous, Farrah Pompilus, Stefan J Cano, Patrick Marquis, Stanley Cohan, Myla D Goldman, Kiren Kresa-Reahl, Jennifer Petrillo, Carmen Castrillo-Viguera, Diego Cadavid, Shih-Yin Chen

Articles, Abstracts, and Reports

Background and objective: The 12-item Multiple Sclerosis Walking Scale (MSWS-12) is a patient-reported outcome instrument that quantifies the progressive loss of walking ability from the patient perspective. However, previous psychometric analyses indicated floor and ceiling effects across the multiple sclerosis severity spectrum. This study aimed to address floor effects by creating a gait module that can be used in conjunction with the MSWS-12 for better measurement of treatment benefit in the higher functioning multiple sclerosis population.

Methods: We used a step-wise mixed methods study design, with relapsing-remitting multiple sclerosis patients (wave 1,

Results: Thirty-seven walking ability concepts were identified, and …

Transcriptional Regulatory Networks Underlying Gene Expression Changes In Huntington's Disease., Seth A Ament, Jocelynn R Pearl, Jeffrey P Cantle, Robert M Bragg, Peter J Skene, Sydney R Coffey, Dani E Bergey, Vanessa C Wheeler, Marcy E Macdonald, Nitin S Baliga, Jim Rosinski, Leroy E Hood, Jeffrey B Carroll, Nathan D Price

Articles, Abstracts, and Reports

Transcriptional changes occur presymptomatically and throughout Huntington's disease (HD), motivating the study of transcriptional regulatory networks (TRNs) in HD We reconstructed a genome-scale model for the target genes of 718 transcription factors (TFs) in the mouse striatum by integrating a model of genomic binding sites with transcriptome profiling of striatal tissue from HD mouse models. We identified 48 differentially expressed TF-target gene modules associated with age- and CAG repeat length-dependent gene expression changes in

Fenestration Of The Proximal Left Ovarian Vein., Mayank Patel, Joe Iwanaga, Rod J Oskouian, R Shane Tubbs

Articles, Abstracts, and Reports

A fenestration in the left ovarian vein was found in a fresh-frozen female cadaver. The opening did not have any vessels or additional anatomical structures passing through it. The ovarian vein is also referred to as the female gonadal vein. This type of anatomical variation is clinically relevant in procedures that deal with the manipulation of the gonadal veins, specifically conditions such as ovarian vein thrombosis, ovarian vein stenosis, and pelvic congestion syndrome.

The Current Trend Of The Translational Research Paradigm., Paul J Choi, R Shane Tubbs, Rod J Oskouian

Articles, Abstracts, and Reports

The translational research paradigm is a process of discovering basic science concepts and applying the knowledge in clinical practice, aiming to improve patient care. The stages involved in the paradigm form a complex network of shared knowledge amongst research collaborators, including patients. This nature of the paradigm allows those involved to work together effectively. However, the translational research paradigm is often overlooked by many scientists, educators, and research institutions. Hence, a large amount of comprehensive and hugely invested research projects fail to make a scientific impact. We aim to outline and describe this paradigm in order to aid in the …

Telomerase Reverse Transcriptase Promoter Alterations Across Cancer Types As Detected By Next-Generation Sequencing: A Clinical And Molecular Analysis Of 423 Patients., Maria Schwaederle, Nithya Krishnamurthy, Gregory A Daniels, David E Piccioni, Santosh Kesari, Paul T Fanta, Richard B Schwab, Sandip P Patel, Barbara A Parker, Razelle Kurzrock

Articles, Abstracts, and Reports

BACKGROUND: Telomerase reverse transcriptase (TERT) promoter mutations that may affect telomerase activity have recently been described in human malignancies. The purpose of this study was to investigate the clinical correlates of TERT promoter abnormalities in a large cohort of patients with diverse cancers.

METHODS: This study analyzed TERT promoter alterations and clinical characteristics of 423 consecutive patients for whom molecular testing by next-generation sequencing was performed between August 2014 and July 2015.

RESULTS: Of the 423 patients, 61 (14.4%) had TERT promoter mutations, and this placed TERT promoter alterations among the most prevalent aberrations after tumor protein 53 (TP53; 39%) …

Features And Outcomes Of Methamphetamine-Associated Pulmonary Arterial Hypertension., Roham T Zamanian, Haley Hedlin, Paul Greuenwald, David M Wilson, Joshua I Segal, Michelle Jorden, Kristina Kudelko, Juliana Liu, Andrew Hsi, Allyson Rupp, Andrew J Sweatt, Rubin Tuder, Gerald J Berry, Marlene Rabinovitch, Ramona L Doyle, Vinicio De Jesus Perez, Steven M Kawut

Articles, Abstracts, and Reports

RATIONALE: Although amphetamines are recognized as "likely" agents to cause drug- and toxin-associated pulmonary arterial hypertension (PAH), (meth)amphetamine-associated PAH (Meth-APAH) has not been well described.

OBJECTIVES: To prospectively characterize the clinical presentation, histopathology, and outcomes of Meth-APAH compared with those of idiopathic PAH (iPAH).

METHODS: We performed a prospective cohort study of patients with Meth-APAH and iPAH presenting to the Stanford University Pulmonary Hypertension Program between 2003 and 2015. Clinical, pulmonary angiography, histopathology, and outcomes data were compared. We used data from the Healthcare Cost and Utilization Project to estimate the epidemiology of PAH in (meth)amphetamine users hospitalized in California. …

Emerging Cellular Therapies For Glioblastoma Multiforme., Paul J Choi, R Shane Tubbs, Rod J Oskouian

Articles, Abstracts, and Reports

Glioblastoma multiforme (GBM) is the most common type of malignant primary brain cancer in adults. It is composed of highly malignant cells that display metastatic and angiogenic characteristics, making it resistant to current first-line chemotherapy with temozolomide, an alkylating agent. Despite many years of research, GBM remains poorly responsive to multiple available therapies, giving GBM patients, who receive the conventional combination of chemoradiotherapies and surgical resection, a dismal prognosis. There is growing evidence that the conventional systemic chemotherapeutic agents for GBM are ineffective in improving the disease progression. We aim to explore the emerging cellular therapies which may play a …

Clinical Feasibility Of Umbilical Cord Tissue-Derived Mesenchymal Stem Cells In The Treatment Of Multiple Sclerosis., Neil H Riordan, Isabela Morales, Giselle Fernández, Nicole Allen, Neal E Fearnot, Michael E Leckrone, Dedra Jones Markovich, Darla Mansfield, Dorita Avila, Amit N Patel, Santosh Kesari, Jorge Paz Rodriguez

Articles, Abstracts, and Reports

BACKGROUND: Multiple sclerosis (MS) is a progressively debilitating neurological condition in which the immune system abnormally erodes the myelin sheath insulating the nerves. Mesenchymal stem cells (MSC) have been used in the last decade to safely treat certain immune and inflammatory conditions.

METHODS: A safety and feasibility study was completed on the use of umbilical cord MSC (UCMSC) as a treatment for MS. In this 1-year study, consenting subjects received seven intravenous infusions of 20 × 10

RESULTS: Twenty subjects were enrolled in this study. No serious adverse events were reported. Of the mild AEs denoted as possibly related to …

Partnership Between Islam And Palliative Care At Swedish Health Services, Hodo Mohamud, Renee Rassilyer-Bomers, Samantha Bohn, Greg Malone, Hilaire Thompson (Faculty Capstone Project Committee Chair), Eeeseung Byun (Committee Member), Margaret Heitkemper (Committee Member)

Articles, Abstracts, and Reports

The spiritual practice of Islam is considered one of the three major monotheistic religions. Islam is the second largest religion in the world with 1.6 billion followers; about 3.5 million of those live in the U.S.1 The number of Muslims in the U.S. is projected to double by 2030.1 Additionally, the number of adults age 65 and older in the U.S. is projected to double from 46 million today to over 98 million by 2060.2 As the U.S. population ages, many healthcare workers are often too overwhelmed to handle the varying and intricate social, economic, familial, spiritual, and cultural needs …

Randomized Phase Ii Trial Of Autologous Dendritic Cell Vaccines Versus Autologous Tumor Cell Vaccines In Metastatic Melanoma: 5-Year Follow Up And Additional Analyses., Robert O. Dillman, Andrew N Cornforth, Gabriel I Nistor, Edward F Mcclay, Thomas T Amatruda, Carol Depriest

Articles, Abstracts, and Reports

BACKGROUND: Despite improved survival following checkpoint inhibitors, there is still a potential role for anti-cancer therapeutic vaccines. Because of biological heterogeneity and neoantigens resulting from each patient's mutanome, autologous tumor may be the best source of tumor-associated antigens (TAA) for vaccines. Ex vivo loading of autologous dendritic cells with TAA may be associated with superior clinical outcome compared to injecting irradiated autologous tumor cells. We conducted a randomized phase II trial to compare autologous tumor cell vaccines (TCV) and autologous dendritic cell vaccines (DCV) loaded with autologous TAA.

METHODS: Short-term autologous tumor cell lines were established from metastatic tumor. Vaccines …

Reprogrammed Lipid Metabolism In Bladder Cancer With Cisplatin Resistance., Min Young Lee, Austin Yeon, Muhammad Shahid, Eunho Cho, Vikram Sairam, Robert Figlin, Khae-Hwan Kim, Jayoung Kim

Articles, Abstracts, and Reports

Due to its tendency to recur and acquire chemoresistance quickly, bladder cancer (BC) remains to be an elusive and difficult disease. Patients with recurrent and chemoresistant BC have an extremely poor prognosis. One possible approach that may provide insightful and valuable information regarding resistance mechanisms is looking into the lipid metabolism of BC cells. Metabolism of lipids is essential for cancer cells and is associated with the regulation of a variety of key cellular processes and functions. This study conducted a comparative lipidomic profiling of two isogenic human T24 bladder cancer cell lines, one of which is clinically characterized as …

Associations Between Neighbourhood Characteristics And Depression: A Twin Study., Hannah Cohen-Cline, Shirley A A Beresford, Wendy Elizabeth Barrington, Ross L Matsueda, Jon Wakefield, Glen E Duncan

Articles, Abstracts, and Reports

BACKGROUND: Depression is an important contributor to the global burden of disease. Besides several known individual-level factors that contribute to depression, there is a growing recognition that neighbourhood environment can also profoundly affect mental health. This study assessed associations between three neighbourhood constructs-socioeconomic deprivation, residential instability and income inequality-and depression among adult twin pairs. The twin design is used to examine the association between neighbourhood constructs and depression, controlling for selection factors (ie, genetic and shared environmental factors) that have confounded purported associations.

METHODS: We used multilevel random-intercept Poisson regression among 3738 same-sex twin pairs from a community-based twin registry …

Conserved Brain Myelination Networks Are Altered In Alzheimer's And Other Neurodegenerative Diseases., Mariet Allen, Xue Wang, Jeremy D Burgess, Jens Watzlawik, Daniel J Serie, Curtis S Younkin, Thuy Nguyen, Kimberly G Malphrus, Sarah Lincoln, Minerva M Carrasquillo, Charlotte Ho, Paramita Chakrabarty, Samantha Strickland, Melissa E Murray, Vivek Swarup, Daniel H Geschwind, Nicholas T Seyfried, Eric B Dammer, James J Lah, Allan I Levey, Todd E Golde, Cory Funk, Hongdong Li, Nathan D Price, Ronald C Petersen, Neill R Graff-Radford, Steven G Younkin, Dennis W Dickson, Julia R Crook, Yan W Asmann, Nilüfer Ertekin-Taner

Articles, Abstracts, and Reports

INTRODUCTION: Comparative transcriptome analyses in Alzheimer's disease (AD) and other neurodegenerative proteinopathies can uncover both shared and distinct disease pathways.

METHODS: We analyzed 940 brain transcriptomes including patients with AD, progressive supranuclear palsy (PSP; a primary tauopathy), and control subjects.

RESULTS: We identified transcriptional coexpression networks implicated in myelination, which were lower in PSP temporal cortex (TCX) compared with AD. Some of these associations were retained even after adjustments for brain cell population changes. These TCX myelination network structures were preserved in cerebellum but they were not differentially expressed in cerebellum between AD and PSP. Myelination networks were downregulated in …

Immediate Versus Delayed Insertion Of The Levonorgestrel Intrauterine Device In Postpartum Adolescents: A Randomized Pilot Study., Reni Soon, Katie Mcguire, Jennifer Salcedo, Bliss Kaneshiro

Articles, Abstracts, and Reports

This pilot study assessed the feasibility of conducting a larger randomized controlled trial comparing the proportion of adolescents using a levonorgestrel intrauterine device (LNG IUD) at six months postpartum when it is inserted immediately after vaginal delivery (within 10 minutes after placental expulsion) compared to insertion four to six weeks postpartum. Pregnant adolescents (14 to 19 years) who desired a LNG IUD for postpartum contraception were randomized to insertion of the LNG IUD either within 10 minutes of delivery of the placenta or at 4-6 weeks postpartum. Study follow-up visits were conducted at 4-6 weeks postpartum, 10 weeks postpartum, and …

2017 Well Being Trust Annual Report, Well Being Trust

Articles, Abstracts, and Reports

Tyler Norris, writing in the 2017 Well Being Trust Annual Report:

This is a promising moment for our nation, as the importance of mental health and well-being become obvious to growing numbers of Americans and awareness of mental health disorders, addiction and related conditions are emerging from the shadows and moving onto the front page. For a long time, diseases of despair— depression, anxiety, addiction, thoughts of suicide—have been stigmatized as character flaws or moral failures, and even today are widely viewed as a personal matter, something to be covered up, kept out of sight, never talked about. The responsibility …