Medicine and Health Sciences Commons^™

Mfge8 Links Absorption Of Dietary Fatty Acids With Catabolism Of Enterocyte Lipid Stores Through Hnf4Γ-Dependent Transcription Of Ces Enzymes, Ritwik Datta, Mohammad A Gholampour, Christopher D Yang, Regan Volk, Sinan Lin, Michael J Podolsky, Thomas Arnold, Florian Rieder, Balyn W Zaro, Michael Verzi, Richard Lehner, Nada Abumrad, Carlos O Lizama, Kamran Atabai

2020-Current year OA Pubs

Enterocytes modulate the extent of postprandial lipemia by storing dietary fats in cytoplasmic lipid droplets (cLDs). We have previously shown that the integrin ligand MFGE8 links absorption of dietary fats with activation of triglyceride (TG) hydrolases that catabolize cLDs for chylomicron production. Here, we identify CES1D as the key hydrolase downstream of the MFGE8-αvβ5 integrin pathway that regulates catabolism of diet-derived cLDs. Mfge8 knockout (KO) enterocytes have reduced CES1D transcript and protein levels and reduced protein levels of the transcription factor HNF4γ. Both Ces1d and Hnf4γ KO mice have decreased enterocyte TG hydrolase activity coupled with retention of TG in …

Structural And Functional Analysis Of Human Pannexin 2 Channel, Zhihui He, Yonghui Zhao, Michael J Rau, James A J Fitzpatrick, Rajan Sah, Hongzhen Hu, Peng Yuan

2020-Current year OA Pubs

The pannexin 2 channel (PANX2) participates in multiple physiological processes including skin homeostasis, neuronal development, and ischemia-induced brain injury. However, the molecular basis of PANX2 channel function remains largely unknown. Here, we present a cryo-electron microscopy structure of human PANX2, which reveals pore properties contrasting with those of the intensely studied paralog PANX1. The extracellular selectivity filter, defined by a ring of basic residues, more closely resembles that of the distantly related volume-regulated anion channel (VRAC) LRRC8A, rather than PANX1. Furthermore, we show that PANX2 displays a similar anion permeability sequence as VRAC, and that PANX2 channel activity is inhibited …

An Online Repository For Pre-Clinical Imaging Protocols (Pips), Seth T Gammon, Hongyu An, James D Quirk, Kooresh Shoghi, Et Al.

2020-Current year OA Pubs

Providing method descriptions that are more detailed than currently available in typical peer reviewed journals has been identified as an actionable area for improvement. In the biochemical and cell biology space, this need has been met through the creation of new journals focused on detailed protocols and materials sourcing. However, this format is not well suited for capturing instrument validation, detailed imaging protocols, and extensive statistical analysis. Furthermore, the need for additional information must be counterbalanced by the additional time burden placed upon researchers who may be already overtasked. To address these competing issues, this white paper describes protocol templates …

Epigenetic And Transcriptomic Characterization Reveals Progression Markers And Essential Pathways In Clear Cell Renal Cell Carcinoma, Yige Wu, Nadezhda V Terekhanova, Wagma Caravan, Nataly Naser Al Deen, Preet Lal, Siqi Chen, Chia-Kuei Mo, Song Cao, Yize Li, Alla Karpova, Ruiyang Liu, Yanyan Zhao, Andrew Shinkle, Ilya Strunilin, Cody Weimholt, Kazuhito Sato, Lijun Yao, Mamatha Serasanambati, Xiaolu Yang, Matthew Wyczalkowski, Houxiang Zhu, Daniel Cui Zhou, Reyka G Jayasinghe, Daniel Mendez, Michael C Wendl, Melissa A Reimers, Russell K Pachynski, Aadel A Chaudhuri, Milan G Chheda, Benjamin D Humphreys, James J Hsieh, Li Ding, Feng Chen, Et Al.

2020-Current year OA Pubs

Identifying tumor-cell-specific markers and elucidating their epigenetic regulation and spatial heterogeneity provides mechanistic insights into cancer etiology. Here, we perform snRNA-seq and snATAC-seq in 34 and 28 human clear cell renal cell carcinoma (ccRCC) specimens, respectively, with matched bulk proteogenomics data. By identifying 20 tumor-specific markers through a multi-omics tiered approach, we reveal an association between higher ceruloplasmin (CP) expression and reduced survival. CP knockdown, combined with spatial transcriptomics, suggests a role for CP in regulating hyalinized stroma and tumor-stroma interactions in ccRCC. Intratumoral heterogeneity analysis portrays tumor cell-intrinsic inflammation and epithelial-mesenchymal transition (EMT) as two distinguishing features of tumor …

Validation Of A Farsi Version Of The Eating Pathology Symptoms Inventory (F-Epsi) Among Iranian Adolescents, Reza N Sahlan, Jessica F Saunders, Ellen E Fitzsimmons-Craft

2020-Current year OA Pubs

PURPOSE: Limited research has validated eating pathology assessments in Iranian adolescent boys and girls. In particular, the measures that have been validated do not capture both boys' and girls' eating behaviors in adolescence. The purpose of the current study was to validate a Farsi version of the Eating Pathology Symptoms Inventory (F-EPSI) for use in Iranian adolescents.

METHODS: Participants (N = 913; 85.3% girls) were adolescents who completed a battery of questionnaires including the F-EPSI. In addition, F-EPSI data for Iranian adolescents were compared with those of previously published data of adult Iranian college students.

RESULTS: Confirmatory Factor Analysis (CFA) …

Median Nerve Stimulation For Treatment Of Tics: Randomized, Controlled, Crossover Trial, Ann M Iverson, Amanda L Arbuckle, Keisuke Ueda, David Y Song, Emily C Bihun, Jonathan M Koller, Michael Wallendorf, Kevin J. Black

2020-Current year OA Pubs

A prior study showed that rhythmic, but not arrhythmic, 12 Hz stimulation of the median nerve (MNS) entrained the sensorimotor cortex EEG signal and found that 10 Hz MNS improved tics in Tourette syndrome (TS). However, no control condition was tested, and stimulation blocks lasted only 1 min. We set out to replicate the TS results and to test whether tic improvement occurs by the proposed cortical entrainment mechanism. Preregistration was completed at ClinicalTrials.gov, under number NCT04731714. Thirty-two people with TS, age 15-64, completed two study visits with repeated MNS on and off blocks in random order, one visit for …

Incidence Of Pneumocystis Pneumonia In Immunocompromised Patients Without Human Immunodeficiency Virus On Intravenous Pentamidine Prophylaxis: A Systematic Review And Meta-Analysis, Chia-Yu Chiu, Patrick R Ching

2020-Current year OA Pubs

BACKGROUND: Trimethoprim-sulfamethoxazole (TMP-SMX) is a first-line

METHOD: We performed a systematic review and meta-analysis to estimate breakthrough PCP incidence and adverse reactions in HIV-uninfected immunocompromised patients receiving IVP. MEDLINE, Embase, Web of Science, Cochrane Library, and ClinicalTrials.gov were searched from their inception until 15 December 2022.

RESULTS: The pooled incidence of breakthrough PCP with IVP was 0.7% (95% CI, 0.3-1.4%, 16 studies, 3025 patients) and was similar when used as first-line prophylaxis (0.5%; 95% CI, 0.2-1.4%, 7 studies, 752 patients). The pooled incidence of adverse reactions was 11.3% (95% CI, 6.7-18.6%, 14 studies, 2068 patients). The pooled adverse event-related discontinuation …

Calpain Activity Is Negatively Regulated By A Kctd7-Cullin-3 Complex Via Non-Degradative Ubiquitination, Jaiprakash Sharma, Shalaka Mulherkar, Uan-I Chen, Yan Xiong, Lakshya Bajaj, Byoung-Kyu Cho, Young Ah Goo, Hon-Chiu Eastwood Leung, Kimberley F Tolias, Marco Sardiello

2020-Current year OA Pubs

Calpains are a class of non-lysosomal cysteine proteases that exert their regulatory functions via limited proteolysis of their substrates. Similar to the lysosomal and proteasomal systems, calpain dysregulation is implicated in the pathogenesis of neurodegenerative disease and cancer. Despite intensive efforts placed on the identification of mechanisms that regulate calpains, however, calpain protein modifications that regulate calpain activity are incompletely understood. Here we show that calpains are regulated by KCTD7, a cytosolic protein of previously uncharacterized function whose pathogenic mutations result in epilepsy, progressive ataxia, and severe neurocognitive deterioration. We show that KCTD7 works in complex with Cullin-3 and Rbx1 …

Imc-Denoise: A Content Aware Denoising Pipeline To Enhance Imaging Mass Cytometry, Peng Lu, Karolyn A Oetjen, Diane E Bender, Marianna B Ruzinova, Daniel A C Fisher, Kevin G Shim, Russell K Pachynski, W Nathaniel Brennen, Stephen T Oh, Daniel C Link, Daniel L J Thorek

2020-Current year OA Pubs

Imaging Mass Cytometry (IMC) is an emerging multiplexed imaging technology for analyzing complex microenvironments using more than 40 molecularly-specific channels. However, this modality has unique data processing requirements, particularly for patient tissue specimens where signal-to-noise ratios for markers can be low, despite optimization, and pixel intensity artifacts can deteriorate image quality and downstream analysis. Here we demonstrate an automated content-aware pipeline, IMC-Denoise, to restore IMC images deploying a differential intensity map-based restoration (DIMR) algorithm for removing hot pixels and a self-supervised deep learning algorithm for shot noise image filtering (DeepSNiF). IMC-Denoise outperforms existing methods for adaptive hot pixel and background …

Antidepressant Augmentation Versus Switch In Treatment-Resistant Geriatric Depression, Eric J Lenze, Pilar Cristancho, Torie R Gettinger, Emily Lenard, J Philip Miller, Ginger E Nicol, Vy T Pham, Lei Yang, Et Al.

2020-Current year OA Pubs

BACKGROUND: The benefits and risks of augmenting or switching antidepressants in older adults with treatment-resistant depression have not been extensively studied.

METHODS: We conducted a two-step, open-label trial involving adults 60 years of age or older with treatment-resistant depression. In step 1, patients were randomly assigned in a 1:1:1 ratio to augmentation of existing antidepressant medication with aripiprazole, augmentation with bupropion, or a switch from existing antidepressant medication to bupropion. Patients who did not benefit from or were ineligible for step 1 were randomly assigned in step 2 in a 1:1 ratio to augmentation with lithium or a switch to …

Radiological Society Of North America (Rsna) 3d Printing Special Interest Group (Sig) Clinical Situations For Which 3d Printing Is Considered An Appropriate Representation Or Extension Of Data Contained In A Medical Imaging Examination: Breast Conditions, Elsa M Arribas, Tatiana Kelil, Lumarie Santiago, Arafat Ali, Seetharam C Chadalavada, Leonid Chepelev, Anish Ghodadra, Ciprian N Ionita, Joonhyuk Lee, Prashanth Ravi, Justin R Ryan, Adnan M Sheikh, Frank J Rybicki, David H Ballard, Rsna Special Interest 3d Printing Breast Conditions Voting Group

2020-Current year OA Pubs

The use of medical 3D printing has expanded dramatically for breast diseases. A writing group composed of the Radiological Society of North America (RSNA) Special Interest Group on 3D Printing (SIG) provides updated appropriateness criteria for breast 3D printing in various clinical scenarios. Evidence-based appropriateness criteria are provided for the following clinical scenarios: benign breast lesions and high-risk breast lesions, breast cancer, breast reconstruction, and breast radiation (treatment planning and radiation delivery).

Rapamycin Perfluorocarbon Nanoparticle Mitigates Cisplatin-Induced Acute Kidney Injury, Qingyu Zhou, James D Quirk, Ying Hu, Huimin Yan, Joseph P Gaut, Christine T N Pham, Samuel A Wickline, Hua Pan

2020-Current year OA Pubs

For nearly five decades, cisplatin has played an important role as a standard chemotherapeutic agent and been prescribed to 10-20% of all cancer patients. Although nephrotoxicity associated with platinum-based agents is well recognized, treatment of cisplatin-induced acute kidney injury is mainly supportive and no specific mechanism-based prophylactic approach is available to date. Here, we postulated that systemically delivered rapamycin perfluorocarbon nanoparticles (PFC NP) could reach the injured kidneys at sufficient and sustained concentrations to mitigate cisplatin-induced acute kidney injury and preserve renal function. Using fluorescence microscopic imaging and fluorine magnetic resonance imaging/spectroscopy, we illustrated that rapamycin-loaded PFC NP permeated and …

Integrated Analysis Of Genomic And Transcriptomic Data For The Discovery Of Splice-Associated Variants In Cancer, Kelsy C Cotto, Yang-Yang Feng, Avinash Ramu, Megan Richters, Sharon L Freshour, Zachary L Skidmore, Huiming Xia, Joshua F Mcmichael, Jason Kunisaki, Katie M Campbell, Timothy Hung-Po Chen, Emily B Rozycki, Douglas Adkins, Siddhartha Devarakonda, Sumithra Sankararaman, Yiing Lin, William C Chapman, Christopher A Maher, Vivek Arora, Ramaswamy Govindan, Obi L Griffith, Malachi Griffith, Et Al.

2020-Current year OA Pubs

Somatic mutations within non-coding regions and even exons may have unidentified regulatory consequences that are often overlooked in analysis workflows. Here we present RegTools ( www.regtools.org ), a computationally efficient, free, and open-source software package designed to integrate somatic variants from genomic data with splice junctions from bulk or single cell transcriptomic data to identify variants that may cause aberrant splicing. We apply RegTools to over 9000 tumor samples with both tumor DNA and RNA sequence data. RegTools discovers 235,778 events where a splice-associated variant significantly increases the splicing of a particular junction, across 158,200 unique variants and 131,212 unique …

Macrophages Promote Repair Of Inner Hair Cell Ribbon Synapses Following Noise-Induced Cochlear Synaptopathy, Vijayprakash Manickam, Dinesh Y Gawande, Andrew R Stothert, Anna C Clayman, Lyudmila Batalkina, Mark E Warchol, Kevin K Ohlemiller, Tejbeer Kaur

2020-Current year OA Pubs

Resident cochlear macrophages rapidly migrate into the inner hair cell synaptic region and directly contact the damaged synaptic connections after noise-induced synaptopathy. Eventually, such damaged synapses are spontaneously repaired, but the precise role of macrophages in synaptic degeneration and repair remains unknown. To address this, cochlear macrophages were eliminated using colony stimulating factor 1 receptor (CSF1R) inhibitor, PLX5622. Sustained treatment with PLX5622 in

Advance Care Planning And Health-Related Quality Of Life In Huntington Disease: Results From A Multicenter National Study, Leonard L Sokol, Jonathan P Troost, Danny Bega, Benzi M Kluger, Holly G Prigerson, Martha Nance, Samuel Frank, Joel S Perlmutter, Praveen Dayalu, David Cella, Noelle E Carlozzi

2020-Current year OA Pubs

OBJECTIVE: With Huntington disease (HD), a fatal neurodegenerative disease where the prevalence of suicidal thoughts and behavior (STB) remains elevated as compared to other neurological disorders, it is unknown whether STB and health-related quality of life (HRQoL) affect plans for the end of life or more broadly, advance care planning (ACP). Conversely, it is unknown whether ACP would provoke future changes to STB and HRQoL. Therefore, we sought to evaluate whether STB and HRQoL patient-reported outcomes (PROs) contribute to ACP and whether ACP relates to changes in STB and HRQoL at 24 months.

METHODS: HD-validated clinician- and patient-assessments (i.e., HRQoL …

Acceptability And User Experiences Of A Patient-Held Smart Card For Antenatal Services In Nigeria: A Qualitative Study, Ijeoma Uchenna Itanyi, Juliet Iwelunmor, John Olajide Olawepo, Semiu Gbadamosi, Alexandra Ezeonu, Adaeze Okoli, Amaka Grace Ogidi, Donaldson Conserve, Byron Powell, Chima Ariel Onoka, Echezona Edozie Ezeanolue

2020-Current year OA Pubs

BACKGROUND: Poor maternal, newborn and child health outcomes remain a major public health challenge in Nigeria. Mobile health (mHealth) interventions such as patient-held smart cards have been proposed as effective solutions to improve maternal health outcomes. Our objectives were to assess the acceptability and experiences of pregnant women with the use of a patient-held smartcard for antenatal services in Nigeria.

METHODS: Using focus group discussions, qualitative data were obtained from 35 pregnant women attending antenatal services in four Local Government Areas (LGAs) in Benue State, Nigeria. The audio-recorded data were transcribed and analyzed using framework analysis techniques such as the …

Cross-Modal Functional Connectivity Supports Speech Understanding In Cochlear Implant Users, Amanda M Fullerton, Deborah A Vickers, Robert Luke, Addison N Billing, David Mcalpine, Heivet Hernandez-Perez, Jonathan E Peelle, Jessica J M Monaghan, Catherine M Mcmahon

2020-Current year OA Pubs

Sensory deprivation can lead to cross-modal cortical changes, whereby sensory brain regions deprived of input may be recruited to perform atypical function. Enhanced cross-modal responses to visual stimuli observed in auditory cortex of postlingually deaf cochlear implant (CI) users are hypothesized to reflect increased activation of cortical language regions, but it is unclear if this cross-modal activity is "adaptive" or "mal-adaptive" for speech understanding. To determine if increased activation of language regions is correlated with better speech understanding in CI users, we assessed task-related activation and functional connectivity of auditory and visual cortices to auditory and visual speech and non-speech …

Vaccine Effectiveness Against Influenza A(H3n2)-Associated Hospitalized Illness: United States, 2022, Mark W Tenforde, Jennie H Kwon, Et Al.

2020-Current year OA Pubs

BACKGROUND: The COVID-19 pandemic was associated with historically low influenza circulation during the 2020-2021 season, followed by an increase in influenza circulation during the 2021-2022 US season. The 2a.2 subgroup of the influenza A(H3N2) 3C.2a1b subclade that predominated was antigenically different from the vaccine strain.

METHODS: To understand the effectiveness of the 2021-2022 vaccine against hospitalized influenza illness, a multistate sentinel surveillance network enrolled adults aged ≥18 years hospitalized with acute respiratory illness and tested for influenza by a molecular assay. Using the test-negative design, vaccine effectiveness (VE) was measured by comparing the odds of current-season influenza vaccination in influenza-positive …

Exercise Training To Improve Brain Health In Older People Living With Hiv: Study Protocol For A Randomized Controlled Trial, Sarah Cooley, Brittany M Nelson, Alexander Rosenow, Elizabeth Westerhaus, W Todd Cade, Dominic N Reeds, Florin Vaida, Kevin E Yarasheski, Robert H Paul, Beau M Ances

2020-Current year OA Pubs

BACKGROUND: With the advent of antiretrovirals, people living with HIV are living near-normal lifespans. However, people living with HIV are at greater risk of experiencing cognitive impairment and reduced brain integrity despite well-controlled viremia. A robust literature supports exercise interventions as a method of improving cognition and structural brain integrity in older individuals without HIV. The effects of exercise on cardiometabolic, neurocognitive, and neural structures in middle-aged to older people living with HIV are less well known, with few prospective studies examining these measures.

OBJECTIVE: This prospective randomized clinical trial will examine the effects of a 6-month exercise training intervention …

Allosteric Effects Of E. Coli Ssb And Recr Proteins On Reco Protein Binding To Dna, Min Kyung Shinn, Sumit K Chaturvedi, Alexander G Kozlov, Timothy M Lohman

2020-Current year OA Pubs

Escherichia coli single stranded (ss) DNA binding protein (SSB) plays essential roles in DNA maintenance. It binds ssDNA with high affinity through its N-terminal DNA binding core and recruits at least 17 different SSB interacting proteins (SIPs) that are involved in DNA replication, recombination, and repair via its nine amino acid acidic tip (SSB-Ct). E. coli RecO, a SIP, is an essential recombination mediator protein in the RecF pathway of DNA repair that binds ssDNA and forms a complex with E. coli RecR protein. Here, we report ssDNA binding studies of RecO and the effects of a 15 amino acid …

The Association Of Center Volume With Transplant Outcomes In Selected High-Risk Groups In Kidney Transplantation, Massini Merzkani, Su-Hsin Chang, Haris Murad, Krista L Lentine, Munis Mattu, Mei Wang, Vangie Hu, Bolin Wang, Yazen Al-Hosni, Obadah Alzahabi, Omar Alomar, Jason Wellen, Tarek Alhamad

2020-Current year OA Pubs

BACKGROUND: In context of increasing complexity and risk of deceased kidney donors and transplant recipients, the impact of center volume (CV) on the outcomes of high-risk kidney transplants(KT) has not been well determined.

METHODS: We examined the association of CV and outcomes among 285 U.S. transplant centers from 2000-2016. High-risk KT were defined as recipient age ≥ 70 years, body mass index (BMI) ≥ 35 kg/m

RESULTS: Two hundred fifty thousand five hundred seventy-four KT were analyzed. Compared to high CV, recipients with BMI ≥ 35 kg/m

CONCLUSIONS: Recipients of high-risk KT with BMI ≥ 35 kg/m

Internal Capsule Microstructure Mediates The Relationship Between Childhood Maltreatment And Ptsd Following Adulthood Trauma Exposure, Samantha A. Wong, Stacey L. House, Deanna M. Barch, Et Al.

2020-Current year OA Pubs

No abstract provided.

Imaging Of Brain Structural And Functional Effects In People With Human Immunodeficiency Virus, Erin E O'Connor, Edith V Sullivan, Linda Chang, Dima A Hammoud, Tony W Wilson, Ann B Ragin, Christina S Meade, Jennifer Coughlin, Beau M Ances

2020-Current year OA Pubs

Before the introduction of antiretroviral therapy, human immunodeficiency virus (HIV) infection was often accompanied by central nervous system (CNS) opportunistic infections and HIV encephalopathy marked by profound structural and functional alterations detectable with neuroimaging. Treatment with antiretroviral therapy nearly eliminated CNS opportunistic infections, while neuropsychiatric impairment and peripheral nerve and organ damage have persisted among virally suppressed people with HIV (PWH), suggesting ongoing brain injury. Neuroimaging research must use methods sensitive for detecting subtle HIV-associated brain structural and functional abnormalities, while allowing for adjustments for potential confounders, such as age, sex, substance use, hepatitis C coinfection, cardiovascular risk, and others. …

Gemc1 And Mcidas Interactions With Swi/Snf Complexes Regulate The Multiciliated Cell-Specific Transcriptional Program, Michael Lewis, Tao Cheng, Moe R Mahjoub, Et Al.

2020-Current year OA Pubs

Multiciliated cells (MCCs) project dozens to hundreds of motile cilia from their apical surface to promote the movement of fluids or gametes in the mammalian brain, airway or reproductive organs. Differentiation of MCCs requires the sequential action of the Geminin family transcriptional activators, GEMC1 and MCIDAS, that both interact with E2F4/5-DP1. How these factors activate transcription and the extent to which they play redundant functions remains poorly understood. Here, we demonstrate that the transcriptional targets and proximal proteomes of GEMC1 and MCIDAS are highly similar. However, we identified distinct interactions with SWI/SNF subcomplexes; GEMC1 interacts primarily with the ARID1A containing …

Targeted Delivery Of Therapeutic Agents To The Mouse Brain Using A Stereotactic-Guided Focused Ultrasound Device, Zhongtao Hu, Yaoheng Yang, Dezhuang Ye, Si Chen, Yan Gong, Chinwendu Chukwu, Hong Chen

2020-Current year OA Pubs

Existing protocols of focused ultrasound (FUS) combined with microbubble-mediated blood-brain barrier (BBB) opening (FUS-BBBO) in preclinical research require expensive ultrasound equipment and complex operating procedures. We developed a low-cost, easy-to-use, and precise FUS device for small animal models in preclinical research. Here, we provide a detailed protocol for building the FUS transducer, attaching the transducer to a stereotactic frame for precise brain targeting, applying the integrated FUS device to perform FUS-BBBO in mice, and evaluating the FUS-BBBO outcome. For complete details on the use and execution of this protocol, please refer to Hu et al. (2022).

Inducing T Cell Dysfunction By Chronic Stimulation Of Car-Engineered T Cells Targeting Cancer Cells In Suspension Cultures, Mehmet Emrah Selli, Jack H Landmann, Corvin Arveseth, Nathan Singh

2020-Current year OA Pubs

Several pre-clinical models reveal that chronic chimeric antigen receptor (CAR) stimulation drives a dysfunctional state that mimics in vivo failure. In this protocol, we describe steps to induce T cell dysfunction by persistent and long-term stimulation of CAR-engineered T cells using antigen-expressing cancer cells in suspension cultures. We first described a validated method for manufacturing of CAR T cells, followed by a detailed method for chronic stimulation of CAR T cells and a strategy to evaluate these cells during the process of chronic stimulation. For complete details on the use and execution of this protocol, please refer to Singh et …

Comparing Gene Panels For Non-Retinal Indications: A Systematic Review, Rebecca Procopio, Jose S Pulido, Kammi B Gunton, Zeba A Syed, Daniel Lee, Mark L Moster, Robert Sergott, Julie A Neidich, Margaret M Reynolds

2020-Current year OA Pubs

IMPORTANCE: The options for genetic testing continue to grow for ocular conditions, including optic atrophy, anterior segment dysgenesis, cataracts, corneal dystrophy, nystagmus, and glaucoma. Gene panels can vary in content and coverage, as we and others have evaluated in inherited retinal disease (IRD).

OBJECTIVE: To describe gene panel testing options for inherited eye disease phenotypes and their differences. This review is important for making diagnostic decisions.

EVIDENCE REVIEW: A licensed, certified genetic counselor (RP) used Concert Genetics and the search terms optic atrophy, corneal dystrophy, cataract, glaucoma, anterior segment dysgenesis, microphthalmia/anophthalmia, and nystagmus to identify available testing options performed by …

Zoledronic Acid Blocks Overactive Kir6.1/Sur2-Dependent Katp Channels In Skeletal Muscle And Osteoblasts In A Murine Model Of Cantú Syndrome, Rosa Scala, Fatima Maqoud, Conor Mcclenaghan, Theresa M Harter, Maria Grazia Perrone, Antonio Scilimati, Colin G Nichols, Domenico Tricarico

2020-Current year OA Pubs

Cantú syndrome (CS) is caused by the gain of function mutations in the

Astrocytic Apoe4 Removal Confers Cerebrovascular Protection Despite Increased Cerebral Amyloid Angiopathy, Monica Xiong, Chao Wang, Maud Gratuze, Fareeha Saadi, Xin Bao, Megan E Bosch, Choonghee Lee, Hong Jiang, Javier Remolina Serrano, Ernesto R Gonzales, Michal Kipnis, David M Holtzman

2020-Current year OA Pubs

BACKGROUND: Alzheimer Disease (AD) and cerebral amyloid angiopathy (CAA) are both characterized by amyloid-β (Aβ) accumulation in the brain, although Aβ deposits mostly in the brain parenchyma in AD and in the cerebrovasculature in CAA. The presence of CAA can exacerbate clinical outcomes of AD patients by promoting spontaneous intracerebral hemorrhage and ischemia leading to CAA-associated cognitive decline. Genetically, AD and CAA share the ε4 allele of the apolipoprotein E (APOE) gene as the strongest genetic risk factor. Although tremendous efforts have focused on uncovering the role of APOE4 on parenchymal plaque pathogenesis in AD, mechanistic studies investigating the role …

Animal Models And Their Role In Imaging-Assisted Co-Clinical Trials, Donna M Peehl, Li Ding, Kooresh I Shoghi, Et Al.

2020-Current year OA Pubs

The availability of high-fidelity animal models for oncology research has grown enormously in recent years, enabling preclinical studies relevant to prevention, diagnosis, and treatment of cancer to be undertaken. This has led to increased opportunities to conduct co-clinical trials, which are studies on patients that are carried out parallel to or sequentially with animal models of cancer that mirror the biology of the patients' tumors. Patient-derived xenografts (PDX) and genetically engineered mouse models (GEMM) are considered to be the models that best represent human disease and have high translational value. Notably, one element of co-clinical trials that still needs significant …