Medicine and Health Sciences Commons^™

A Scoping Review Of Interventions To Address Financial Toxicity In Pediatric And Adult Patients And Survivors Of Cancer, Christina Ping, D Carolina Andrade, Ashley Housten, Michelle Doering, Eliana Goldstein, Mary C Politi

2020-Current year OA Pubs

BACKGROUND: Financial toxicity (FT) is a common and significant challenge for people with cancer, impacting immediate clinical outcomes such as treatment adherence, as well as long-term outcomes such as quality of life and mortality. Multiple studies have tested interventions to address FT and develop recommendations for their implementation.

METHODS: In this scoping review, we analyzed thirty-six studies across 35,405 participants examining institution-based interventions for FT in both pediatric and adult patients and survivors of cancer in the U.S.

RESULTS: Common interventions included: financial navigation (n = 15), direct financial/medical assistance (n = 8), financial counseling or coaching (n = 5), …

Linear Growth During Treatment With A Simplified, Combined Protocol: Secondary Analyses Of Severely Wasted Children 6-59 Months In The Compas Cluster Randomized Controlled Trial, Grace Heymsfield, Kevin Stephenson, Zachary Tausanovitch, André Briend, Marko Kerac, Heather Stobaugh, Jeanette Bailey, Suvi T Kangas

2020-Current year OA Pubs

A simplified, combined protocol treats children with moderate acute malnutrition (MAM), defined by mid-upper arm circumference (MUAC) of <  125 and ≥ 115 mm and no oedema, with 1 daily sachet of ready-to-use therapeutic food (RUTF) and those with severe acute malnutrition (SAM), defined by MUAC <  115 mm and/or oedema, with two daily sachets of RUTF. This protocol was previously shown to result in non-inferior recovery compared to standard treatment that used higher, weight-based RUTF dosing among children with SAM and ready-to-use supplementary food (RUSF) for MAM in a cluster-based randomised controlled trial in Kenya and South Sudan. We conducted a secondary analysis of this trial to compare linear growth among children admitted with MUAC <  115 mm. Linear and ponderal growth were calculated from admission to discharge and visualised using aggregate growth curves. HAZ change adjusted for admission characteristics was negative across the course of treatment but similar across arms [-0.21 ± 0.18 SE in the standard arm, -0.24 ± 0.18 SE in simplified; difference (95% confidence interval) 0.03 (-0.12, 0.18)]. The unadjusted mean ± SE linear growth velocity from admission to discharge was 1.8 ± 0.7 mm/week in the standard arm compared to 1.7 ± 0.7 mm/week in the simplified arm [difference = 0.09 (-0.36, 0.53)] and similar in adjusted analysis. MUAC and weight gain velocities were not significantly different by treatment arm. Reducing the RUTF dose prescribed to children during SAM treatment does not appear to affect linear growth or other growth velocities during treatment.

Model For End Stage Liver Disease Excluding International Normalized Ratio Predicts Severe Right Ventricular Failure After Heartmate 3 Implantation In A Contemporary Cohort, David S Lambert, Ana María Picó, Justin D Vincent, Elena Deych, Erin Coglianese, Joel D Schilling, Justin M Vader, Bin Q Yang

2020-Current year OA Pubs

BACKGROUND: Right ventricular failure (RVF) after left ventricular assist devices is associated with significant morbidity and mortality. Therefore, identifying patients at risk for severe RVF is important for clinical decision-making. Current risk prediction models were not developed in contemporary populations with left ventricular assist devices and have limited clinical applicability. In this study, we sought to evaluate whether the Model for End Stage Liver Disease Excluding International Normalized Ratio (MELD-XI) can predict severe RVF after HeartMate 3 implantation.

METHODS: We retrospectively analyzed all adult patients who received HeartMate 3 left ventricular assist devices as initial implantation at 2 academic medical …

The Implications Of The American Board Of Radiology's Decision To Relinquish Its Specialty Board Designation On Prospective Authorized Medical Physicists (Amps) And Radiation Safety Officers (Rsos), Christopher J Tien, Samantha J Simiele, Joann I Prisciandaro, Jacqueline E Zoberi, Y Jessica Huang, William A Hinchcliffe, Hania A Al-Hallaq

2020-Current year OA Pubs

In order to independently supervise the medical use of byproduct material, physicists in the United States (US) must legally meet the qualifications defined by the Nuclear Regulatory Commission (NRC) in the 35th part of the tenth title of the Code of Federal Regulations (§ 10 CFR Part 35). The American Board of Radiology (ABR) relinquished its NRC-recognized specialty board (NSB) status at the end of 2023, which eliminated the NSB application pathway for those who earn ABR certification in 2024 and beyond. While these changes in NSB status are not retroactive and will not affect eligibility for diplomates who already …

Unleashing The Power Of Multiomics: Unraveling The Molecular Landscape Of Peripheral Neuropathy, Julie Choi, Zitian Tang, Wendy Dong, Jenna Ulibarri, Elvisa Mehinovic, Simone Thomas, Ahmet Höke, Sheng Chih Jin

2020-Current year OA Pubs

Peripheral neuropathies (PNs) affect over 20 million individuals in the United States, manifesting as a wide range of sensory, motor, and autonomic nerve symptoms. While various conditions such as diabetes, metabolic disorders, trauma, autoimmune disease, and chemotherapy-induced neurotoxicity have been linked to PN, approximately one-third of PN cases remain idiopathic, underscoring a critical gap in our understanding of these disorders. Over the years, considerable efforts have focused on unraveling the complex molecular pathways underlying PN to advance diagnosis and treatment. Traditional methods such as linkage analysis, fluorescence in situ hybridization, polymerase chain reaction, and Sanger sequencing identified initial genetic variants …

Social Determinants Of Health And Health Literacy In Emergency Patients With Diabetic Ketoacidosis, Daniel F Suarez, Ryan M Schneider, Margo Girardi, Gina Larossa, Julianne Yeary, Taylor Kaser, Rachel Ancona, Paulina Cruz Bravo, Richard T Griffey

2020-Current year OA Pubs

INTRODUCTION: Social determinants of health (SDoH) and health literacy have been demonstrated to significantly impact health outcomes. As part of a study of diabetic ketoacidosis (DKA) treatment from the emergency department (ED), we assessed the burden of SDoH and health literacy among patients with DKA to identify potentially modifiable risk factors in the development of DKA.

METHODS: This was an exploratory, prospective, cross-sectional study of adult patients with DKA in a large urban academic ED from March 2023-March 2024. We administered the Centers for Medicare & Medicaid Services Accountable Health Communities Health-Related Social Needs Screening Tool (SNST) and the Brief …

Patient Selection, Ventricular Tachycardia Substrate Delineation, And Data Transfer For Stereotactic Arrhythmia Radioablation: A Clinical Consensus Statement Of The European Heart Rhythm Association Of The European Society Of Cardiology And The Heart Rhythm Society, Katja Zeppenfeld, Clifford Robinson, Et Al.

2020-Current year OA Pubs

Stereotactic arrhythmia radioablation (STAR) is a novel, non-invasive, and promising treatment option for ventricular arrhythmias (VAs). It has been applied in highly selected patients mainly as bailout procedure, when (multiple) catheter ablations, together with anti-arrhythmic drugs, were unable to control the VAs. Despite the increasing clinical use, there is still limited knowledge of the acute and long-term response of normal and diseased myocardium to STAR. Acute toxicity appeared to be reasonably low, but potential late adverse effects may be underreported. Among published studies, the provided methodological information is often limited, and patient selection, target volume definition, methods for determination and …

Independent Origins And Non-Parallel Selection Signatures Of Triclabendazole Resistance In Fasciola Hepatica, Young-Jun Choi, Bruce A Rosa, Martha V Fernandez-Baca, Rodrigo A Ore, John Martin, Pedro Ortiz, Cristian Hoban, Miguel M Cabada, Makedonka Mitreva

2020-Current year OA Pubs

Triclabendazole (TCBZ) is the primary treatment for fascioliasis, a global foodborne zoonosis caused by Fasciola hepatica. Widespread resistance to TCBZ (TCBZ-R) in livestock and a rapid rise in resistant human infections are significant concerns. To understand the genetic basis of TCBZ-R, we sequenced the genomes of 99 TCBZ-sensitive (TCBZ-S) and 210 TCBZ-R adult flukes from 146 bovine livers in Cusco, Peru. We identify genomic regions of high differentiation (F

Tumor Treating Fields Therapy In Platinum-Resistant Ovarian Cancer: Results Of The Engot-Ov50/Gog-3029/Innovate-3 Pivotal Phase 3 Randomized Study, Ignace Vergote, Premal H Thaker, Et Al.

2020-Current year OA Pubs

PURPOSE: Tumor Treating Fields (TTFields) are electric fields that disrupt processes critical for cancer cell viability and tumor progression. The pivotal, phase 3 ENGOT-ov50/GOG-3029/INNOVATE-3 study evaluated efficacy and safety of TTFields therapy with paclitaxel (PTX) vs PTX in patients with platinum-resistant ovarian cancer (PROC).

PATIENTS AND METHODS: Adult patients with PROC with ≤ 5 total prior lines of therapy (LOT), including ≤ 2 prior LOT for platinum-resistant disease, and ECOG PS of 0-1 were randomized 1:1 to receive TTFields (200 kHz; ≥ 18 h/day) + PTX (80 mg/m

RESULTS: Between March 2019 and November 2021, 558 patients (ECOG PS 0, …

Pmp2+ Schwann Cells Maintain The Survival Of Large-Caliber Motor Axons, Mikolaj M Kozlowski, Amy Strickland, Ana Morales Benitez, Robert E Schmidt, A Joseph Bloom, Jeffrey Milbrandt, Aaron Diantonio

2020-Current year OA Pubs

Neurodegenerative diseases of both the central and peripheral nervous system are characterized by selective neuronal vulnerability, i.e., pathology that affects particular types of neurons. While much of this cell type selectivity may be driven by intrinsic differences among the neuron subpopulations, neuron-extrinsic mechanisms such as the selective malfunction of glial support cells may also play a role. Recently, we identified a population of Schwann cells (SCs) expressing

Cell-Matrix Feedback Controls Stretch-Induced Cellular Memory And Fibroblast Activation, Yuan Hong, Xiangjun Peng, Haomin Yu, Delaram Shakiba, Yuxuan Huang, Chengqing Qu, Aliza Mujahid, Yin-Yuan Huang, Jacob A Sandler, Kenneth M Pryse, Justin M Sacks, Elliot L Elson, Guy M Genin, Et Al.

2020-Current year OA Pubs

Mechanical stretch can activate long-lived changes in fibroblasts, increasing their contractility and initiating phenotypic transformations. This activation, critical to wound healing and procedures such as skin grafting, increases with mechanical stimulus for cells cultured in two-dimensional but is highly variable in cells in three-dimensional (3D) tissue. Here, we show that static mechanical stretch of cells in 3D tissues can either increase or decrease fibroblast activation depending upon recursive cell-extracellular matrix (ECM) feedback and demonstrate control of this activation through integrated in vitro and mathematical models. ECM viscoelasticity, signaling dynamics, and cell mechanics combine to yield a predictable, but nonmonotonic, relationship …

Multicilia Dynamically Transduce Sonic Hedgehog Signaling To Regulate Choroid Plexus Functions, Suifang Mao, Michael J Holtzman, Et Al.

2020-Current year OA Pubs

The choroid plexus is a major site for cerebrospinal fluid (CSF) production, characterized by a multiciliated epithelial monolayer that regulates CSF production. We demonstrate that defective choroid plexus ciliogenesis or intraflagellar transport yields neonatal hydrocephalus, at least in part due to increased water channel Aqp1 and ion transporter Atp1a2 expression. We demonstrate choroid plexus multicilia as sensory cilia, transducing both canonical and non-canonical Sonic Hedgehog (Shh) signaling. Interestingly, it is the non-canonical Shh signaling that represses Aqp1 and Atp1a2 expression by the Smoothened (Smo)/Gαi/cyclic AMP (cAMP) pathway. Choroid plexus multicilia exhibit unique ciliary ultrastructure, carrying features of both primary and …

Molecular Basis For Human Respiratory Syncytial Virus Transcriptional Regulator Ns1 Interactions With Med25, Parismita Kalita, Oam Khatavkar, Grace Uwase, Yulia Korshunova, Yuying Hu, Nicole D Wagner, Jian Xu, Jiehong Pan, Jay C Nix, Michael L Gross, Steven L Brody, Dominika Borek, Gaya K Amarasinghe, Jacqueline E Payton, Daisy W Leung

2020-Current year OA Pubs

The Mediator complex facilitates interactions between transcription factors and RNA polymerase II, a process that is required for host gene transcription, including in response to viral infections. Among the many subunits in the Mediator complex, the MED25 subunit has been shown to be a target for viral activators during infection. Here we provide the molecular basis for the interaction between human respiratory syncytial virus (hRSV) nonstructural 1 protein (NS1) and the activator interaction domain (ACID) of MED25. The X-ray crystal structure of the complex revealed that NS1 straddles and binds two faces of MED25 ACID. This interaction is distinct from …

American Society Of Hematology Living Guidelines On Use Of Anticoagulation For Thromboprophylaxis For Patients With Covid-19: Executive Summary, Deborah M Siegal, Kristen M Sanfilippo, Yazan Al Jabiri, Et Al.

2020-Current year OA Pubs

BACKGROUND: COVID-19-related critical and acute illness is associated with an increased risk of venous thromboembolism (VTE). These evidence-based recommendations of the American Society of Hematology (ASH) are intended to support patients, clinicians, and other health care professionals in decisions about using anticoagulation for thromboprophylaxis for patients with COVID-19-related critical illness; patients with COVID-19-related acute illness; and those being discharged from the hospital, who do not have suspected or confirmed VTE.

METHODS: ASH formed a multidisciplinary panel, including patient representatives. The Michael G. DeGroote Cochrane Canada and MacGRADE Centres at McMaster University supported guideline development, including performing systematic reviews (up to …

Tissue-Resident Ccr2+ Macrophage Trem-1/3 Signaling Is Necessary For Monocyte And Neutrophil Recruitment To Injured Hearts, Yuriko Terada, Wenjun Li, Junedh M Amrute, Amit I Bery, Charles R Liu, Venkatrao Nunna, Christian Corbin Frye, Hao Dun, Andrew L Koenig, Hannah P Luehmann, Gyu Seong Heo, Macee C Owen, Alexander N Wein, Yongjian Liu, Jon H Ritter, Sumanth D Prabhu, Ruben G Nava, Andrew E Gelman, Marina Cella, Marco Colonna, Kory J Lavine, Daniel Kreisel

2020-Current year OA Pubs

Triggering receptor expressed on myeloid cells 1 (TREM-1) has been shown to amplify inflammatory signals, such as Toll-like receptor signaling, after infection and sterile injury. While previous studies have demonstrated that TREM-1 activation in circulating immune cells promotes injury, the role of TREM-1 signaling in tissue-resident cells in the context of sterile inflammation remains poorly understood. Here, we used a cardiac transplantation model to dissect how Trem1/3 expression on heart-resident cells regulates sterile inflammation. TREM-1 is expressed in heart-resident C-C chemokine receptor 2 (CCR2)

Metagenomic Signatures Of Extraintestinal Bacterial Infection In The Febrile Term Infant Gut Microbiome, Anna L Deveaux, Carla Hall-Moore, Nurmohammad Shaikh, Meghan Wallace, Carey-Ann D Burnham, David Schnadower, Nathan Kuppermann, Prashant Mahajan, Octavio Ramilo, Phillip I Tarr, Gautam Dantas, Drew J Schwartz

2020-Current year OA Pubs

BACKGROUND: Extraintestinal bacterial infections (EBIs), e.g., urinary tract infection, bacteremia, and meningitis, occur in approximately 10% of febrile infants younger than 60 days. Although many EBI-causing species commonly reside in the infant gut, proof that the digestive system is a pre-infection habitat remains unestablished.

RESULTS: We studied a cohort of febrile term infants <  60 days old who presented to one of thirteen US emergency departments in the Pediatric Emergency Care Applied Research Network from 2016 to 2019. Forty EBI cases and 74 febrile controls matched for age, sex, and race without documented EBIs were selected for analysis. Shotgun sequencing was performed of the gut microbiome and of strains cultured from the gut and extraintestinal site(s) of EBI cases, including blood, urine, and/or cerebrospinal fluid. Using a combination of EBI isolate genomics and fecal metagenomics, we detected an intestinal strain presumptively isogenic to the EBI pathogen (> 99.999% average nucleotide identity) in 63% of infants with EBIs. Although there was no difference in gut microbiome diversity between cases and controls, we observed significantly increased Escherichia coli relative abundance in the gut microbiome of infants with EBIs caused by E. coli. Infants with E. coli …

Supportive Supervision Visits In A Large Community Hypertension Programme In Nigeria: Implementation Methods And Outcomes, Gabriel Lamkur Shedul, Nanna Ripiye, Erica L Jamro, Ikechukwu A Orji, Grace Julcit Shedul, Eugenia N Ugwuneji, Emmanuel Okpetu, Boni M Ale, Samuel Osagie, Abigail S Baldridge, Namratha R Kandula, Mark D Huffman, Dike Ojji, Lisa Hirschhorn

2020-Current year OA Pubs

BACKGROUND: The Hypertension Treatment in Nigeria (HTN) Programme established a system for hypertension diagnosis and management in 60 public primary healthcare facilities in the Federal Capital Territory of Nigeria through the implementation of HEARTS, a multi-level strategy bundle including team-based care led by community health extension workers (CHEWs). To improve HEARTS implementation, supportive supervision was added as an implementation strategy in April 2020.

METHODS: A multidisciplinary supportive supervision team and data collection forms were developed and implemented at HTN-supported sites. Data from April 2020 to December 2023 from supportive supervision visits were used to measure supportive supervision implementation outcomes, including …

A Generalized Epilepsy Network Derived From Brain Abnormalities And Deep Brain Stimulation, Gong-Jun Ji, Nico U F Dosenbach, Et Al.

2020-Current year OA Pubs

Idiopathic generalized epilepsy (IGE) is a brain network disease, but the location of this network and its relevance for treatment remain unclear. We combine the locations of brain abnormalities in IGE (131 coordinates from 21 studies) with the human connectome to identify an IGE network. We validate this network by showing alignment with structural brain abnormalities previously identified in IGE and brain areas activated by generalized epileptiform discharges in simultaneous electroencephalogram-functional magnetic resonance imaging. The topography of the IGE network aligns with brain networks involved in motor control and loss of consciousness consistent with generalized seizure semiology. To investigate therapeutic …

Integrating Mrna Vaccines Into The Attitudes Toward Genomics And Precision Medicine Scale: A Validation Study With A Sample Of 4939 Adults In The Usa, Jenine K Harris, Erin D Solomon, Kari Baldwin, Lauren L Baker, Eu Gene Chin, James M Dubois

2020-Current year OA Pubs

The attitudes toward genomics and precision medicine (AGPM) measure examines attitudes toward activities such as genetic testing, gene editing, and biobanking. This is a useful tool for research on the ethical, legal, and social implications of genomics, a major program within the National Institutes of Health. We updated the AGPM to explore controversies over mRNA vaccines. This brief report examines the factor structure of the updated AGPM using a sample of 4939 adults in the USA. The updated AGPM's seven factors include health benefits, knowledge benefits, and concerns about the sacredness of life, privacy, gene editing, mRNA vaccines, and social …

Therapeutic Interventions For Chronic Central Serous Chorioretinopathy: A Comprehensive Assessment Of Systematic Reviews, Henok Getahun, Rajendra S Apte

2020-Current year OA Pubs

BACKGROUND: A variety of different treatments have been proposed to effectively treat chronic central serous chorioretinopathy but there remains uncertainty regarding the efficacy of a number of treatment options. We aim to evaluate the efficacy of several therapeutic options for chronic central serous chorioretinopathy including photodynamic therapy, conventional laser photocoagulation, subthreshold micropulse laser, selective retina therapy, vascular endothelial growth factor (VEGF) antagonists, and mineralocorticoid receptor antagonists.

METHODS: Pubmed, Embase, and Cochrane databases were searched for systematic reviews and meta-analyses evaluating treatment modalities for chronic central serous chorioretinopathy. Primary outcome measures included improvement in best corrected visual acuity (BCVA) and resolution …

Experiences And Perceptions Of Conditional Cash Incentive Provision And Cessation Among People With Hiv For Care Engagement: A Qualitative Study, Julia Giordano, Jayne Lewis-Kulzer, Lina Montoya, Eliud Akama, Harriet Fridah Adhiambo, Everlyne Nyadieka, Sarah Iguna, Elizabeth A Bukusi, Thomas Odeny, Carol S Camlin, Harsha Thirumurthy, Maya Petersen, Elvin Geng

2020-Current year OA Pubs

BACKGROUND: Conditional cash transfers (CCTs) have been shown to improve retention in HIV care while they are provided, but their long-term effectiveness remains uncertain and effects may be time-limited, with cessation resulting in HIV care engagement deterioration. We explored CCT experiences, perceptions, and effects after cessation to investigate potential mechanisms of this observation and better understand the psychological mechanisms behind CCTs.

METHODS: This qualitative study was nested within a larger trial, AdaPT-R (NCT02338739), focused on HIV care engagement in western Kenya. A subset of participants were purposively sampled from AdaPT-R participants: adults with HIV who had recently started ART, received …

Digital Gait Biomarkers In Parkinson's Disease: Susceptibility/Risk, Progression, Response To Exercise, And Prognosis, Martina Mancini, Gammon M Earhart, Et Al.

2020-Current year OA Pubs

This narrative review examines the utility of gait digital biomarkers in Parkinson's disease (PD) research and clinical trials across four contexts: disease susceptibility/risk, disease progression, response to exercise, and fall prediction. The review of the literature to date suggests that upper body characteristics of gait (e.g., arm swing, trunk motion) may indicate susceptibility/risk of PD, while pace aspects (e.g., gait speed, stride length) are informative for tracking disease progression, exercise response, and fall likelihood. Dynamic stability aspects (e.g., trunk regularity, double-support time) worsen with disease progression but can improve with exercise. Gait variability emerges as a sensitive biomarker across all …

Resiliency In Child-Caregiver Dyads And The Impact On Health Outcomes In Sickle Cell Disease, Jessica A Zavadil, Melissa Azul, Brian D Carpenter, Cecelia Calhoun

2020-Current year OA Pubs

No abstract provided.

Ppdpf: Preventing Kidney Disease Through Nad+, Shin-Ichiro Imai

2020-Current year OA Pubs

Researchers have discovered PPDPF, a critical cellular factor that controls NAD

Distinct Attentional Characteristics Of Neurons With Visual Feature Coding In The Primate Brain, Jie Zhang, Runnan Cao, Xiaocang Zhu, Huihui Zhou, Shuo Wang

2020-Current year OA Pubs

Visual attention and object recognition are two critical cognitive functions that shape our perception of the world. While these neural processes converge in the temporal cortex, the nature of their interactions remains largely unclear. Here, we systematically investigated the interplay between visual attention and stimulus feature coding by training macaques to perform a free-gaze visual search task with natural stimuli. Recording from a large number of units across multiple brain areas, we found that units exhibiting visual feature coding showed stronger attentional modulation of responses and spike-local field potential coherence than units without feature coding. Across brain areas, attention directed …

M3netflow: A Multi-Scale Multi-Hop Graph Ai Model For Integrative Multi-Omic Data Analysis, Heming Zhang, S Peter Goedegebuure, Li Ding, David Denardo, Ryan C Fields, Michael Province, Yixin Chen, Philip Payne, Fuhai Li

2020-Current year OA Pubs

Multi-omic data-driven studies are at the forefront of precision medicine by characterizing complex disease signaling systems across multiple views and levels. The integration and interpretation of multi-omic data are critical for identifying disease targets and deciphering disease signaling pathways. However, it remains an open problem due to the complex signaling interactions among many proteins. Herein, we propose a multi-scale multi-hop multi-omic network flow model, M3NetFlow, to facilitate both hypothesis-guided and generic multi-omic data analysis tasks. We evaluated M3NetFlow using two independent case studies: (1) uncovering mechanisms of synergy of drug combinations (hypothesis/anchor-target guided multi-omic analysis) and (2) identifying biomarkers of …

Compositional Variation In Eye-Infiltrating Immune Cells Distinguishes Human Uveitis Subtypes, Christian Concepcion, Yu Xia, Yulia Korshunova, Gregory W Bligard, Amal Taylor, Michael A Paley, Philip A Ruzycki, Lynn M Hassman

2020-Current year OA Pubs

Uveitis is a heterogeneous group of ocular inflammatory diseases that respond inadequately to empiric therapy, underscoring the need to define pathophysiologic subtypes. Toward this goal, we applied single-cell transcriptional and immune receptor profiling to ocular fluid biopsies from 23 patients with diverse clinical features. We found that a subset of ocular T cells undergoes local clonal expansion, indicating that antigens trigger uveitis in some patients. Infiltrates from HLA-B27 associated acute anterior uveitis (HLA-B27 AAU) were enriched in myeloid cells and innate immune signaling pathways, while chronic uveitis featured prominent adaptive immune cells and transcriptional programs, indicating that immunologic features distinguish …

Delivering Guideline-Directed Medical Therapy For Heart Failure With Reduced Ejection Fraction As An Over-Encapsulated Polypill: Rationale And Protocol For The Combo-Hf-X Pilot Crossover Randomised Clinical Trial, Colette Dejong, Mark D Huffman, Anubha Agarwal, Et Al.

2020-Current year OA Pubs

INTRODUCTION: A four-drug regimen of guideline-directed medical therapy (GDMT) for heart failure with reduced ejection fraction (HFrEF) is underused, in part due to prescriber inertia and low patient adherence. Although fixed-dose combination pills ('polypills') have improved adherence and clinical outcomes for other conditions, there are no polypills available that combine multiple classes of GDMT for HFrEF. Pharmacy-level over-encapsulation, in which several tablets are combined into one capsule, offers an opportunity to create customised HFrEF polypills with the goal of improving delivery of HFrEF therapies.

METHODS AND ANALYSIS: In the COMBO-HF-X pilot crossover randomised clinical trial, we will enrol 30-40 patients …

Protocol To Study Inter-Tissue Communication Between The Hypothalamus And White Adipose Tissue And Lifespan Using A Chemogenetic Approach In Aged Mice, Kyohei Tokizane, Shin-Ichiro Imai

2020-Current year OA Pubs

Here, we present a protocol for assessing the impact of a chemogenetic manipulation in a subpopulation of the hypothalamic neurons on aging and lifespan control using a mouse model developed specifically for this purpose. We describe steps for stereotaxic viral injection and assess inter-tissue communication between protein phosphatase 1 regulatory subunit 17 (Ppp1r17)-expressing neurons in the dorsomedial hypothalamus and white adipose tissue. We then detail procedures for lifespan measurements following chemogenetic manipulation in aged mice. For complete details on the use and execution of this protocol, please refer to Tokizane et al.

The Night's Watch: Exploring How Sleep Protects Against Neurodegeneration, Samira Parhizkar, David M Holtzman

2020-Current year OA Pubs

Sleep loss is often regarded as an early manifestation of neurodegenerative diseases given its common occurrence and link to cognitive dysfunction. However, the precise mechanisms by which sleep disturbances contribute to neurodegeneration are not fully understood, nor is it clear why some individuals are more susceptible to these effects than others. This review addresses critical unanswered questions in the field, including whether sleep disturbances precede or result from neurodegenerative diseases, the functional significance of sleep changes during the preclinical disease phase, and the potential role of sleep homeostasis as an adaptive mechanism enhancing resilience against cognitive decline and neurodegeneration.