Medicine and Health Sciences Commons^™

An Acetylation-Dependent Switch Underlies Host Disease Tolerance During Streptococcal Infection, Sumit Kumar Paudel, Sowmya Gannavaram, Michael G Caparon, Wei Xu

2020-Current year OA Pubs

Building on our finding that Streptococcus pyogenes pyruvate dehydrogenase (PDH) suppresses host disease tolerance (DT) via short-chain fatty acid (SCFA)-mediated modulation of host acetyl-CoA and IL-10 levels, we characterize the global transcriptomic and epigenetic mechanisms underlying this immunometabolic manipulation. Combining new histological and ultrastructural analyses with an in-depth re-analysis of single-cell and bulk RNA-seq datasets to more comprehensively characterize the DT response, we show that PDH deficiency is associated with broad immunologic rewiring, characterized by intracellular bacterial containment within phagocytes, expansion of pro-resolving myeloid cells, and altered cell-cell communication. Metabolic analysis of ΔPdh-infected tissues revealed a shift away from acetyl-CoA …

Decreased Metallothionein-3 Expression In The Human Spinal Cord Is A Common Feature Of Amyotrophic Lateral Sclerosis And Multiple Sclerosis, Adam P Gunn, James B W Hilton, Soumya Mukherjee, Jeffrey R Liddell, Stephen W Mercer, Catriona A Mclean, Colin L Masters, Peter J Crouch, Blaine R Roberts

2020-Current year OA Pubs

Amyotrophic lateral sclerosis (ALS) and multiple sclerosis (MS) are devastating adult-onset neurological diseases with distinct pathological manifestations. Although growing evidence implicates copper dysregulation in both diseases, our understanding of this connection remains incomplete. In this study, we investigated metallothionein-3 (MT3), which is a key regulator of copper metabolism in the central nervous system (CNS), and its relationship to copper in the ALS and MS spinal cord. Using combined quantitative mass spectrometry approaches and immunohistochemical observations, we found a significant decrease in ALS and MS spinal cord MT3 levels compared to controls. This was correlated with levels of copper and MT3-copper …

Glucagon-Like Peptide-1 Receptor Agonists And Risk Of Substance Use Disorders Among Us Veterans With Type 2 Diabetes: Cohort Study, Miao Cai, Taeyoung Choi, Yan Xie, Ziyad Al-Aly

2020-Current year OA Pubs

OBJECTIVES: To investigate whether initiation of glucagon-like peptide-1 (GLP-1) receptor agonists is associated with both reduced risks of incident alcohol, cannabis, cocaine, nicotine, opioid, and other substance use disorders (SUDs) in people with no history of SUDs (protocol 1) and with reduced risk of SUD related adverse clinical outcomes among people with a pre-existing SUD (protocol 2).

DESIGN: Emulation of eight parallel, new user, active comparator target trials using electronic health records: seven trials for each incident SUD outcome (protocol 1) and one trial for adverse outcomes in people with pre-existing SUD (protocol 2).

SETTING: US Department of Veterans Affairs. …

Sodium Content Of Packaged Foods And Beverages In Nigeria: A Cross-Sectional Comparative Study With Who Global Sodium Benchmarks, Kenya, And South Africa, Adedayo E Ojo, Alexandra Jones, Kylie Howes, Vanessa Alfa, Anthony Orji, Oluwafemi A Stephen, Carla Pool, Alex Kibet, Fraser Taylor, Diederick E Grobbee, Bruce Neal, Mark D Huffman, Dike B Ojji, Sanne A E Peters

2020-Current year OA Pubs

High intake of processed foods, especially those with high sodium content, is a contributor to hypertension and cardiovascular disease. This study aimed to compare the sodium content of packaged foods and beverages in Nigeria to WHO Global Sodium Benchmarks and similar products in Kenya and South Africa. The study examined packaged foods from major retail stores in the capital cities of the Federal Capital Territory, Kano, and Ogun states in Nigeria from November 2020 to March 2021. Benchmark values were based on the 2021 WHO Global Sodium Benchmarks. We used secondary data from packaged food surveys conducted in South Africa …

Exploring The Role Of Social Networks In Youth Mental Health, Nicholas Szoko, Alexander Riley, Jacquelin Rankine, Alison J Culyba

2020-Current year OA Pubs

Social network analysis (SNA) offers an innovative approach to understand youths' complex social support systems. Growing work highlights links between youths' social networks and mental health. We used SNA to examine associations between social network characteristics and psychological empowerment, depression, anxiety, and post-traumatic stress among youth living in areas with concentrated disadvantage. We administered egocentric social network surveys in which youth (i.e., egos) enumerated individuals in their social network (i.e., alters), answered questions about each alter, and described how alters were connected. We measured psychological empowerment and mental health symptoms with validated instruments. There were 111 youth in the analytic …

Sex-Related Differences In Clinical Profile, Management, And Outcomes Of Patients With Type A And B Acute Aortic Dissection: Observations From Irad, Elizabeth Jackson, Andreina Carbone, Sherene Shalhub, Chih-Wen Pai, Marek Ehrlich, Toru Suzuki, G Chad Hughes, Anil Bhan, Rumi Faizer, Antonio Cittadini, Alan Braverman, Eric Isselbacher, Kim Eagle, Christoph Nienaber, Eduardo Bossone

2020-Current year OA Pubs

BACKGROUND: Available data about sex differences in patients with acute aortic dissection (AAD) are scant and conflicting. The aim of this study is to assess sex-related differences in clinical characteristics, presentation, diagnostic findings, management, and outcomes among patients with type A (TA-AAD) and type B AAD (TB-AAD).

METHODS: Data about 11 586 patients enrolled in the IRAD (International Registry of Acute Aortic Dissection) from 1996 to 2022, were analyzed; 7819 (67.5%) experienced TA-AAD and 3867 (33.0%) TB-AAD. Men and women were compared with regard to diagnosis, treatment, and in-hospital and long-term survival.

RESULTS: One third of patients were women (TA-AAD, …

Building Capacity On Hypertension Management In Nigeria, Shivani Mishra, Daphne Lew, Et Al.

2020-Current year OA Pubs

No abstract provided.

Shiga Toxin-Producing Escherichia Coli Outbreak In Canadian Daycare Centers, Mohamed Eltorki, Oluwatimilehin O Ajayi, Jina Seok, Jianling Xie, Francesco A Rizzuti, Byron M Berenger, Phillip I Tarr, Andrew T Pavia, Kate Snedeker, Silviu Grisaru, Otto G Vanderkooi, Linda Chui, Gillian A M Tarr, Gemma Vomiero, Stephen B Freedman

2020-Current year OA Pubs

IMPORTANCE: Shiga toxin-producing Escherichia coli (STEC) infections have significant morbidity, with 15% to 20% of children developing hemolytic uremic syndrome (HUS), more than half of whom require kidney replacement therapy (KRT).

OBJECTIVE: To describe health care resource utilization, clinical outcomes, and outcomes associated with daily laboratory monitoring for thrombotic microangiopathy (TMA) in a large point-source STEC outbreak.

DESIGN, SETTING, AND PARTICIPANTS: This retrospective cohort study was conducted among a population-based cohort of individuals exposed to a contaminated food item served in 11 childcare centers in Calgary, Alberta, Canada, on August 29, 2023. Children and adults with confirmed STEC infection linked …

Trends In Mammography Use Among Women Aged 40 To 74 Years In The Us, 2002-2022, Syed Mahfuz Al Hasan, Debbie L Bennett, Adetunji T Toriola

2020-Current year OA Pubs

IMPORTANCE: Understanding how prior policies, systemic factors, and public health events have shaped mammography use among US women is essential for interpreting the 2024 US Preventive Services Task Force (USPSTF) recommendation update and identifying gaps to inform equitable public health strategies.

OBJECTIVE: To analyze mammography use trends in US women aged 40 to 49 and 50 to 74 years from 2002 to 2022 and assess variation by sociodemographic, health care access, behavioral, and geographic factors, including associations with the 2009 USPSTF recommendation and the COVID-19 pandemic.

DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional study used data from the Behavioral Risk Factor …

The Relationship Between Apparent Potentiation And The Magnitude Of The Control Response, Joe Henry Steinbach, Gustav Akk

2020-Current year OA Pubs

The effect of a potentiating drug on ion channel function is typically evaluated by comparing current responses to the control agonist in the presence and absence of the potentiator. Differences in ratios of responses are then taken as proof of distinct potentiation properties when comparing modulation by different compounds. In these experiments, the concentration of the agonist is typically kept low to generate a small fractional control response. The precise relative magnitude of the control response is, however, not standardized among labs and can range from a concentration producing a response equal to just 2% of maximal (EC2) to over …

Cell Type-Specific Gene Regulatory Atlas Prioritizes Drug Targets And Repurposable Medicines In Alzheimer's Disease, Yunxiao Ren, Ming Hu, Yang E Li, Andrew A Pieper, Jeffrey Cummings, Feixiong Cheng

2020-Current year OA Pubs

Alzheimer's disease (AD) is a complex and poorly understood neurodegenerative disorder that lacks sufficiently effective treatments. Computational and integrative analyses that leverage multiomic data provide a promising strategy to uncover disease mechanisms and identify therapeutic opportunities. Here, we develop a cell type-specific regulatory atlas of the human middle temporal gyrus via leveraging single-nucleus RNA-seq (1,197,032 nuclei) and ATAC-seq (740,875 nuclei) data sets from 84 donors across four stages of AD neuropathological change (ADNC). We observe differential gene expression for six major cell types intensified at severe ADNC. Integrating peak-to-gene linkages and motif enrichment analyses, we reconstruct transcription factor (TF)-target gene …

Media Reporting Of The 2024 Us Preventive Services Task Force Mammography Guideline Update, Tamar Parmet, Yue Li, Joseph Cappella, Laura D Scherer, Erika A Waters, Ashley J Housten

2020-Current year OA Pubs

No abstract provided.

The Win Ratio For Evaluating Edoxaban Vs Dalteparin For Cancer-Associated Venous Thromboembolism: An Analysis Of The Randomized Hokusai Venous Thromboembolism Cancer Trial, Nick Van Es, Luuk J J Scheres, Kristen M Sanfilippo, Harry Büller, Marc Carrier, Marcello Di Nisio, Michael Grosso, Renato D Lopes, William F Mcintyre, Bjorn Redfors, Annelise Segers, Peter Verhamme, Jeffrey I Weitz, Patrick M Bossuyt, Deborah M Siegal

2020-Current year OA Pubs

BACKGROUND: The Hokusai Venous Thromboembolism (VTE) Cancer trial demonstrated that edoxaban was noninferior to dalteparin for the treatment of cancer-associated venous VTE.

OBJECTIVES: We reanalyzed the trial using the win ratio, an approach that evaluates a composite of outcomes in a hierarchical order.

METHODS: Forty-nine thrombosis experts ranked 10 outcomes in order of clinical importance from all-cause death (most important) to clinically relevant nonmajor bleeding (least important). We performed unmatched pairwise comparisons between participants on edoxaban and those on dalteparin at 6- and 12-month follow-up. Within each pair, edoxaban was assigned a win, loss, or tie according to the hierarchy …

Single Zonular Fiber Extraction And Characterization: A Platform For Biomechanical, Biochemical And Structural Analyses, Riley Forinash, Sean Staggs, Steven Bassnett, Juan Rodriguez

2020-Current year OA Pubs

Zonular fibers are essential for suspending the lens within the eye and, in primates, for transmitting forces generated by the ciliary body to drive ocular accommodation. Despite their biomechanical importance, the response of these fibers to sudden strains, and the molecular basis of their exceptional durability remain poorly understood. This is due, in part, to the absence of tools for studying them in isolation. Here, we present a custom-built, cost-effective apparatus designed to isolate, manipulate, and characterize individual zonular fibers under controlled physical and chemical conditions. The apparatus enables quantification of elastic moduli, stress-relaxation behavior, Poisson's ratio, and response to …

Mapping Charge Interactions In Intrinsically Disordered Proteins, Michael Phillips, Andrea Holla, Magdalena Wojtas, Aritra Chowdhury, Andrea Sottini, Sebastian L B König, Natalie Mutter, Nick Lamb, Jonathan Huihui, Monika Lopko, Andrea Soranno, Daniel Nettels, Andrzej Ożyhar, Benjamin Schuler, Kingshuk Ghosh

2020-Current year OA Pubs

Intrinsically disordered proteins (IDPs) are often rich in charged residues, and electrostatic interactions have a pronounced effect on their conformational distributions, interactions and functions. However, attaining quantitative understanding of electrostatics is challenging because of the sequence-specific arrangement of charges in the chain, the long-range nature of electrostatic interactions, charge screening, and the condensation of counterions-effects that all need to be taken into account self-consistently. Here, analytically tractable quantitative models are developed to predict ensemble average distances between any pair of residues in IDPs as a function of sequence and salt concentration, explicitly considering charge patterning. These models are tested systematically …

Real-World Experience With Selexipag In Patients With Pulmonary Arterial Hypertension: Treatment Patterns And Outcomes Across Baseline Risk Strata (Sphere And Exposure Studies), Pilar Escribano Subias, Murali M Chakinala, Et Al.

2020-Current year OA Pubs

BACKGROUND: Treatment strategies for pulmonary arterial hypertension (PAH) depend on patients' 1-year mortality risk; however, real-world practices and outcomes remain inadequately described.

OBJECTIVE: We aimed to investigate real-world experience with selexipag, an oral selective prostacyclin I2 receptor agonist used to treat PAH.

METHODS: This analysis of two large, prospective, observational studies: SPHERE (NCT03278002; USA; completed) and EXPOSURE (EUPAS19085; Europe and Canada; ongoing, data cutoff November 2021) included adults newly initiating selexipag with follow-up available.

RESULTS: Of 1366 selexipag users, 894 met eligibility criteria. At selexipag initiation, the median (Q1-Q3) age was 61 (48-70) years and the time since diagnosis was …

Accuracy And Reliability Of Artery-Vein Differentiation In Small-Field Macular Oct Angiography, Haneen Alfauri, Tugce Ilayda Turer, Cyriac Manjaly, Aditya Santoki, Senyue Hao, Marin Woronets, Chao Zhou, Rithwick Rajagopal

2020-Current year OA Pubs

PURPOSE: Accurate artery-vein (AV) differentiation in small-field macular optical coherence tomography angiography (OCTA) remains challenging due to a lack of standardized guidelines. We propose and validate criteria for

APPROACH: Small field-of-view (FOV) OCTA scans were analyzed using established AV criteria for large-field (

RESULTS: A total of 465 vessels from 20 healthy eyes were evaluated across 3 pseudo-branching orders using the criteria for OCTA. Annotators achieved high accuracy (95.1%, 92.3%) and strong intra/inter-rater reliability (

CONCLUSIONS: Accurate and reproducible AV labeling is feasible in

Cdk4/6 Inhibition Mitigates Chemotherapy-Induced Expansion Of Tp53-Mutant Clonal Hematopoiesis, Irenaeus C C Chan, Giulia Petrone, J Scott Beeler, Duc Tran, Griffen Mustion, Catrina Fronick, Carlos Cruchaga, Kelly L Bolton, Et Al.

2020-Current year OA Pubs

Therapy-related myeloid neoplasm (tMN) is a fatal consequence of exposure to cytotoxic therapy administered in the treatment of cancer. Individuals with pre-existing TP53 clonal hematopoiesis (CH) are at high risk of tMN, with avoidance of therapy being the only strategy to reduce tMN risk. Here, in four randomized clinical trials, we show that the CDK4/6 inhibitor trilaciclib, given in conjunction with a variety of chemotherapeutic regimens and across diverse populations of patients with cancer, mitigates chemotherapy-related expansion of CH clones with mutations in DNA damage response genes, including TP53. This finding was also observed in a syngeneic mouse model of …

Active Bone Marrow Dose Reconstruction In A Large-Scale Cohort Study Of Cancer Patients Treated With Photon Radiotherapy, Keith T Griffin, Kishan J Pithadia, Yeon Soo Yeom, Lior Braunstein, Kelly L Bolton, Lindsay M Morton, Choonsik Lee

2020-Current year OA Pubs

BACKGROUND: Previous studies have investigated the dose-response relationship between external beam radiotherapy (EBRT) and leukemia by reconstructing the mean active bone marrow (ABM) dose as part of the exposure assessment. However, no prior study has leveraged electronic medical records (EMR) to reconstruct ABM dose and dose-volume in an EBRT patient population.

PURPOSE: To support future studies on the relationship between radiation exposure and adverse health effects among EBRT patients, we demonstrate methods to retrospectively calculate ABM dose and dose-volume metrics in a large patient cohort using EMR.

METHODS: We retrieved complete EMR for 639 individuals (five pediatric and 634 adult) …

Cholecalciferol (Vitamin D3) Is An Agonist Of The Alzheimer's Disease-Associated Immune Receptor Trem2, Hunter B Dean, Ryan A Tuckey, Rory A Greer, Jessica A Greven, Shan-Zhong Yang, Daniel S Elston, Gunnar N Eastep, Yuwei Song, Thomas J Brett, Yuhua Song, Erik D Roberson

2020-Current year OA Pubs

Triggering Receptor Expressed on Myeloid Cells 2 (TREM2) is one of the strongest genetic risk factors for late-onset Alzheimer's disease (AD). Several TREM2 ligands are known, including charged lipids and AD-associated proteins like apolipoprotein E and amyloid-β, but the full range of endogenous ligands for TREM2 remains unknown. Here we combined virtual screening of the Human Metabolome Database with molecular dynamics simulations, binding free energy estimation, and biolayer interferometry to identify novel TREM2 ligands and map their binding sites. Cholecalciferol, the unmodified parent form of vitamin D3, emerged as a top candidate. Structural modeling indicated that cholecalciferol binds TREM2 at …

Durability Of Efficacy, Safety, And Quality Of Life 5 Years After Valoctocogene Roxaparvovec Gene Transfer For Severe Hemophilia A: Final Phase 3 Gener8-1 Trial Results, Andrew D Leavitt, Elaine Majerus, Et Al.

2020-Current year OA Pubs

BACKGROUND: Valoctocogene roxaparvovec, a gene therapy for severe hemophilia A, enables endogenous factor VIII (FVIII) expression and confers bleed control.

OBJECTIVES: To present the final 5-year efficacy and safety results from the phase 3 GENEr8-1 trial.

METHODS: Adult men (

RESULTS: Median follow-up was 261.1 weeks; 128 of 134 participants completed the study. For the 112 participants who enrolled from a previous noninterventional study (rollover population), mean ABR for treated bleeds declined by 83.3% (

CONCLUSION: Valoctocogene roxaparvovec provides durable hemostatic efficacy, FVIII activity, and improved health-related quality of life for ≥5 years, with no new safety signals.

Parkinson's Disease As A Somato-Cognitive Action Network Disorder, Jianxun Ren, Evan M Gordon, Nico U F Dosenbach, Et Al.

2020-Current year OA Pubs

Parkinson's disease (PD) is an incurable neurological disorder that often begins insidiously with sleep disturbances and somatic symptoms, progressing to whole-body motor and cognitive symptoms

Longitudinal Analysis Of Rotator Cuff Repair: Joint Kinematics And Clinical Outcomes, Sujata Khandare, Rebekah L Lawrence, Alena Jalics, Roger Zauel, Vasilios Moutzouros, Eric C Makhni, Stephanie Muh, Michael J Bey

2020-Current year OA Pubs

BACKGROUND: Rotator cuff repair is a common surgical procedure, but postoperative outcomes can be highly variable, and postoperative repair tissue healing remains a significant clinical challenge. Furthermore, the biomechanical effects of rotator cuff repair are not fully understood.

METHODS: Twenty-two participants scheduled for arthroscopic rotator cuff repair were evaluated preoperatively and at 3, 12, and 24 months postsurgery. The following data were recorded at each time point: glenohumeral and scapulothoracic kinematics, shoulder strength, and patient-reported measures of pain and function. Postoperative repair integrity was assessed via magnetic resonance imaging at 3 months and 24 months postsurgery.

RESULTS: At 3 months …

Increased Clinical Frailty Is Associated With Aortic-Related Mortality Following Fenestrated And Branched Endovascular Repair For Thoracoabdominal Aortic Aneurysm, Silvia Chen, Elizabeth Ramirez, Blake E Murphy, Anjali Sribalaskandarajah, Martin Bunker, Joel Kruger, Karina A Newhall, Rebecca A Sorber, Sara L Zettervall, Matthew P Sweet

2020-Current year OA Pubs

OBJECTIVE: Clinical frailty is associated with reduced long-term survival after fenestrated and branched endovascular aortic repair (F/BEVAR). This study assesses the impact of phenotypic clinical frailty on perioperative outcomes and cause of death following F/BEVAR for thoracoabdominal aortic aneurysm.

METHODS: Patients who underwent F/BEVAR at a single institution from 2012 to 2024 were identified. The clinical frailty scale (CFS) was used to determine phenotypic frailty. Patients with a preoperative CFS of ≥4 (vulnerable) and a CFS of < 4 were compared. We used χ

RESULTS: We included 233 patients; 60 (25.8%) had a CFS of ≥4 and 173 (74.2%) had a CFS of < 4. Patients with a CFS of ≥4 were more likely to have chronic obstructive pulmonary disease (53% vs 27%) and were treated for slightly larger aneurysms (72 mm vs 68 mm; P = .04). There were no differences in symptomatic presentation, aneurysm extent, or operative complexity between patient groups. Additionally, there were no differences in perioperative complications including 30-day mortality, stroke, and spinal cord ischemia. Patients with a CFS of ≥4 had an increased length of hospitalization (11.3 days vs 6.9 days; P < .01) and were less likely to return to preoperative functional status (62.7% vs 86.1%; P < .01). The 3-year all-cause and aortic-related mortality rates were 35.2% and 5.7%, respectively. Patients with a CFS of ≥4 had a lower survival at 1 year (74% vs 89%), 3 years (39% vs 73%), and 5 years (25% vs 56%), compared with patients with a CFS of < 4 (P < .01). The most common causes of death among both groups were pulmonary comorbidities (14.0%), oncologic conditions (14.0%), cardiovascular comorbidities (11.2%), and procedure-related complications (11.2%). Patients with a CFS of ≥4 were more likely to die from aortic-related mortality (10.3% vs 5.9%; P = .02), pulmonary comorbidities (15.4 vs 13.2%; P = .04), systemic decline (7.7% vs 1.5%; P = .02), and infection (12.8% vs 7.4%; P = .03). Aortic-related mortality for the entire patient cohort was 2.2% and 5.7% at 1 year and 3 years, respectively. Aortic-related deaths among clinically frail patients were often due to an inability to tolerate further aortic operations (eg, arch repair), and secondary to follow-up nonadherence in patients with a CFS of < 4.

CONCLUSIONS: In an expanded …

Piezo Mechanosensitivity In Chondrocytes Is Differentially Modulated By L-Type And T-Type Voltage-Sensitive Ion Channels, Alireza Savadipour, Gabrielle K Marushack, Robert J Nims, Jaquelin M Garcia-Castorena, Wolfgang Liedtke, Farshid Guilak

2020-Current year OA Pubs

OBJECTIVE: One of the primary factors contributing to OA development is altered or excessive mechanical stress on the joint, which chondrocytes sense in part through the PIEZO mechanosensitive ion channels. These channels activate signaling pathways that result in joint inflammation and cartilage degeneration. In addition to PIEZO channels, voltage-gated calcium (Ca

DESIGN: To better understand the relationship between PIEZO1 and VGCCs, we quantified porcine chondrocytes' intracellular Ca

RESULTS: In primary chondrocytes, nifedipine, an L-type VGCC blocker, reduced PIEZO1 sensitivity to both mechanical compression and pharmacological agonism, while NNC-55, a T-type VGCC blocker, increased PIEZO1 activation in response to both stimuli. …

Synovial Fibroblast Responses To Different Types Of Injury Resulting In Cartilage Repair Or Osteoarthritis, Fraser L Collins, Alexander J Knights, Tristan Maerz, Anke J Roelofs, Cosimo De Bari

2020-Current year OA Pubs

OBJECTIVE: Single-cell RNA-sequencing (scRNA-seq) has advanced our understanding of the heterogeneity of synovial fibroblasts and their roles in tissue repair and osteoarthritis. Here, we compared the fibroblast responses to different types and duration of joint injury in mice.

DESIGN: Published scRNA-seq data of synovial fibroblasts from a model of joint surface injury (JSI, day 6) and two post-traumatic osteoarthritis models, destabilisation of the medial meniscus (DMM, day 7 and 2 months) and anterior cruciate ligament rupture (ACLR, day 7 and day 28), were integrated and analysed using clustering, DEG, gene-set enrichment, regulon, pseudotime trajectory and cell-cycle analyses.

RESULTS: The response …

Aging Reduces Motivation Through Decreased Bdnf Expression In The Ventral Tegmental Area, Hanyue Cecilia Lei, Kyle E Parker, Chao-Cheng Kuo, Carla M Yuede, Jordan G Mccall, Shin-Ichiro Imai

2020-Current year OA Pubs

Age-associated reduced motivation is a hallmark of neuropsychiatric disorders in the elderly. In our rapidly aging societies, it is critical to keep motivation levels high enough to promote healthspan and lifespan. However, how motivation is reduced during aging remains unknown. Here, we used multiple mouse models to evaluate motivation and related affective states in young and old mice. We also compared the effect of social isolation, a common stressor in aged populations, to those of aging. We found that both social isolation and aging decreased motivation in mice, but that Bdnf expression in the ventral tegmental area (VTA) was selectively …

Single-Cell Multi-Omic Techniques Highlight The Diverse Composition And Intercellular Interactions Of The Vestibular Schwannoma Tumor Microenvironment, Shree S Pari, Sangami Pugazenthi, Albert H Kim, Bhuvic Patel

2020-Current year OA Pubs

Vestibular schwannomas (VS) are tumors arising from Schwann cells of the vestibulocochlear nerve, often leading to hearing loss, gait imbalance, and other neurological complications. Recently, molecular profiling of VS using bulk and single-cell transcriptional and epigenetic approaches has reshaped our understanding of VS pathogenesis and challenged the long-standing view of VS being molecularly homogeneous. These integrative, multi-omic approaches reveal significant differences within VS and highlight diverse Schwann cell subpopulations and their interactions with the tumor microenvironment. Interestingly, these analyses also uncover 2 molecularly distinct groups of VS, one containing Schwann cells with an "Injury-like" phenotype that drives VS progression through …

Bacterial Immune Activation Via Supramolecular Assembly With Phage Triggers, Tong Zhang, Yifei Lyu, Christina R Beck, Naseer Iqbal, Renee Barbosa, Alireza Ghanbarpour, Michael T Laub

2020-Current year OA Pubs

Bacteria use diverse mechanisms to protect themselves against phages

Atypical Superotemporal Iris And Retinal Coloboma, Katina N Patterson, Margaret M Reynolds, Gregg T Lueder

2020-Current year OA Pubs

PURPOSE: To report our findings in a patient with an atypical case of supertemporal iris and retinal coloboma, and to assess its systemic associations and potential genetic causes.

OBSERVATIONS: A premature female infant born at 31 weeks gestation presented a left eye superotemporal coloboma affecting both the iris and retina. Systemic abnormalities included a left multicystic kidney, hypoplastic left kidney, atrial septal defect, ventricular septal defect, and mild pulmonary valve stenosis. Whole genome sequencing and mitochondrial deoxyribonucleic acid (DNA) sequencing were performed, and both returned negative results.

CONCLUSIONS AND IMPORTANCE: The absence of genetic findings from the negative results of …