Digital Commons Network^™

Prehospital Cricothyrotomy: A Narrative Review Of Technical, Educational, And Operational Considerations For Procedure Optimization, Aaron J Lacy, Michael J Kim, James L Li, Alexander Croft, Erin E Kane, Jason C Wagner, Philip W Walker, Christine M Brent, Jeremy J Brywczynski, Amanda C Mathews, Brit Long, Alex Koyfman, Bridgette Svancarek

2020-Current year OA Pubs

BACKGROUND: Definitive airway management is a requisite skill in the prehospital setting, most often accomplished with either an endotracheal tube or supraglottic airway. When clinicians encounter a cannot oxygenate and cannot ventilate scenario, a patient's airway still must be secured. Prehospital cricothyrotomy is a high acuity, low frequency procedure used to secure the airway through the anterior neck. Patients who require cricothyrotomy often have significant comorbid conditions and mortality, and there can be a high rate of procedural complications. The ability to perform a cricothyrotomy is within the scope of practice for many prehospital clinicians and mastery of the procedure …

Sleep Disorders Five Years After Acute Provoked Neonatal Seizures, Renée A Shellhaas, Et Al.

2020-Current year OA Pubs

OBJECTIVE: To evaluate whether abnormal sleep is associated with adverse outcomes for children who survived acute provoked neonatal seizures, and their parents.

STUDY DESIGN: This 9-center study prospectively followed newborns with acute provoked seizures. When children reached age 5 years, parents completed the Children's Sleep Habits Questionnaire (CSHQ), the Pediatric Sleep Questionnaire-Sleep Related Breathing Disorders (PSQ-SRBD) subscale, the Vineland Adaptive Behavior Scales-3, and the Hospital Anxiety Depression Scale. Children were also assessed with the Wechsler Preschool and Primary Scale of Intelligence-IV (WPPSI-IV). Spearman correlations and multivariable analyses were used to evaluate risk factors for sleep problems.

RESULTS: The mean CSHQ …

Exploring The Differences Between Brca Mutated And Hrwild-Type High Grade Serous Ovarian Cancer: A Multiomic Analysis, Ayesha B Alvero, Sharon Wu, Alex Farrell, Seongho Kim, John J Wallbillich, Ira Winer, Robert Morris, David Spetzler, Matthew L Anderson, Alberto Puccini, Nathaniel L Jones, Thomas J Herzog, Premal H Thaker, Gil Mor, Radhika P Gogoi

2020-Current year OA Pubs

OBJECTIVE: The purpose of this study was to evaluate the transcriptomic profile of BRCA1 mutant (BRCA1mut) and BRCA2 mutant (BRCA2mut) HGSOC compared to homologous recombination wild-type (HRwt) tumors utilizing the CARIS database.

METHODS: Next-generation and Whole Transcriptome Sequencing (WTS; Caris Life Sciences, Phoenix, AZ) was performed on a total of 2745 HGSOC tumor samples. BRCA mutations were defined as variants resulting in loss-of-function of the protein and HRwt was defined as samples wildtype for aberrations in both BRCA1 and BRCA2, as well as for 28 other HR genes. HRwt group was further classified into HRwt/LOH-low (< 16 %) and HRwt/LOH-high (≥16 %). Genomic analysis consists of mutation analysis and measurements of TMB and MSI. Transcriptomic analysis included identification of Differentially expressed genes (DEGs), GSEA and immune deconvolution.

RESULTS: We identified 519 …

Sacubitril/Valsartan Attenuates Inflammation And Myocardial Fibrosis In Takotsubo-Like Cardiomyopathy, Jiangying Kuang, Zhiyi Jia, Tou Kun Chong, Jian Chen, Kan Liu, Xin Wang, Zhaohua Li, Jing Zhang, Yanru Kong, Lin Deng, Martin Cadieras, Yuanyuan Sun, Rong Sun, Qinghua Lu, Yusheng Liu

2020-Current year OA Pubs

BACKGROUND: Takotsubo syndrome (TTS) primarily manifests as a cardiomyopathy induced by physical or emotional stress, remains a poorly understood condition with no established treatments. In this study, we investigated the potential of sacubitril/valsartan (sac/val) to increase the survival of TTS patients and reduce inflammation and myocardial fibrosis in experimental models.

AIM: This study aimed to evaluate whether sac/val could improve survival rates in TTS patients, mitigate cardiac remodeling in vivo, and explore its anti-inflammatory and antifibrotic mechanisms in vitro.

METHODS: Clinical cases from the Chinese Takotsubo syndrome (ChiTTS) registry were analyzed to assess patient survival rates. In addition, we used …

Genetically Engineered Brain Organoids Recapitulate Spatial And Developmental States Of Glioblastoma Progression, Matthew Ishahak, Rowland H Han, Devi Annamalai, Timothy Woodiwiss, Colin Mccornack, Ryan T Cleary, Patrick A Desouza, Xuan Qu, Sonika Dahiya, Albert H Kim, Jeffrey R Millman

2020-Current year OA Pubs

Glioblastoma (GBM) is an aggressive form of brain cancer that is highly resistant to therapy due to significant intra-tumoral heterogeneity. The lack of robust in vitro models to study early tumor progression has hindered the development of effective therapies. Here, this study develops engineered GBM organoids (eGBOs) harboring GBM subtype-specific oncogenic mutations to investigate the underlying transcriptional regulation of tumor progression. Single-cell and spatial transcriptomic analyses revealed that these mutations disrupt normal neurodevelopment gene regulatory networks resulting in changes in cellular composition and spatial organization. Upon xenotransplantation into immunodeficient mice, eGBOs form tumors that recapitulate the transcriptional and spatial landscape …

Comparison Of 2 Thromboelastography Methods Using Patient And Control Samples, Robert Frick, Brittany Washburn, Dennis Plocher, Jonathan K Zoller, Jason Gillihan, Michael Dombrowski, Charles Eby, Christopher W Farnsworth

2020-Current year OA Pubs

BACKGROUND: Viscoelastic testing at point-of-care is associated with reduced blood loss and blood product transfusions. The ROTEM (Werfen) sigma is a cartridge-based system that may facilitate point-of-care use, but limited studies exist comparing the sigma with the predicated ROTEM delta.

OBJECTIVES: We compared the performance of the ROTEM delta with that of the sigma.

METHODS: Citrated blood was collected from 20 healthy donors and patients during liver transplants (

RESULTS: The coefficient of variation was < 10% for all assays/parameters except for the thromboelastometry with extrinsic activation (EXTEM) clotting time (10.3%) and EXTEM amplitude (A)5 (10.2%). Reference intervals for the delta and sigma were comparable to manufacturer claims. The Pearson r comparing the delta and sigma exceeded .85 for all parameters/assays except for thromboelastometry with cytochalasin D-mediated platelet inhibition (FIBTEM) A10 (.77; 95% CI, .66-.86), FIBTEM A20 (.78; 95% CI, .65-.87), and thromboelastometry with heparinase clotting time (.77; 95% CI, .61-.87). No difference was observed in extrapolated thresholds from the delta-guided algorithm. However, extrapolated sigma A5 parameters for EXTEM were 5 mm lower, and for FIBTEM were 1 mm lower than delta A10 parameters.

CONCLUSION: The ROTEM delta and sigma devices had comparable performance. A negative bias was observed in the FIBTEM assay with lower extrapolated clinical decision points …

Relationships Between Brain Glucose Metabolism Patterns And Impaired Glycemic Status: A Systematic Review Of Fdg-Pet Studies With A Focus On Alzheimer's Disease, Setareh Soltani, Mahsa Dolatshahi, Sara Soltani, Kian Khazaei, Maryam Rahmani, Cyrus A Raji

2020-Current year OA Pubs

It is well-established that individuals with type 2 diabetes have an increased risk of developing cognitive impairment and Alzheimer's disease (AD). However, it is not fully determined how insulin resistance and type 2 diabetes are related to AD-related brain glucose metabolism abnormalities. For this aim, we performed a systematic review of the studies investigating the association between cerebral glucose metabolism and glycemic status, including diabetes, insulin resistance, or hyperglycemia. Medline, Embase, and Cochrane databases were searched (till February 2, 2025). All English full-text papers studying 18F-FDG-PET that investigated the association between cerebral FDG uptake or cerebral metabolism rate and glycemic …

Rapid Development Of An Online Tracker To Communicate The Human Impact Of Abruptly Halting Pepfar Support, Brooke E Nichols, Elvin H Geng, Eric Moakley, Andrew N Phillips, Jeffrey W Imai-Eaton, John Stover, Edinah Mudimu, Anna Grimsrud

2020-Current year OA Pubs

No abstract provided.

Vitamin K Deficiency Bleeding In Children With Cholestatic Liver Disease: A Systematic Review And Meta-Analysis, Anusak Sakwit, Pongpak Pongphitcha, Patcharee Komvilaisak, Masayuki Ochiai, Daijiro Takahashi, Shutaro Suga, Ampaiwan Chuansumrit, Marisol Betensky, Stephen P Pereira, Amber Afzal, C Heleen Van Ommen, Neil Goldenberg, Sasivimol Rattanasiri, Nongnuch Sirachainan

2020-Current year OA Pubs

Vitamin K deficiency (VKD) in cholestatic liver disease affects up to 23% of pediatric patients. While several vitamin K (VK) prophylaxis regimens have been proposed, optimal therapeutic strategies remain undefined. The study aimed to identify the most effective VK prophylaxis for children with cholestatic liver disease. We conducted a systematic review of articles focusing on studies of children aged < 18 years with cholestatic liver disease who reported outcomes of either VKD or vitamin K deficiency bleeding (VKDB) after VK prophylaxis. The articles were sourced from PubMed, Scopus, and Embase. A meta-analysis was performed to determine the prevalence of VKD and the efficacy of each prophylactic protocol in preventing VKD/VKDB. The study was registered on PROSPERO (CRD 42021270048). Of the 889 articles, 37 were selected (2 comparative studies, 6 noncomparative studies, and 29 case reports/series). The results from the comparative studies indicated a lower incidence of VKD in the parenteral than that in the oral VK. The meta-analysis of the noncomparative studies showed the prevalence of VKD in high prothrombin induced by vitamin K absence-II group was 56% (95% CI, 45%-68%;

Spatial Histomorphometry Reveals That Local Peripheral Nerves Modulate But Are Not Required For Skeletal Adaptation To Applied Load In Mice, Alec T Beeve, Mohamed G Hassan, Anna Li, Nicole Migotsky, Matthew J Silva, Erica L Scheller

2020-Current year OA Pubs

Mechanical loading is required for bone health and results in skeletal adaptation to optimize strength. Local nerve axons, particularly within the periosteum, may respond to load-induced biomechanical and biochemical cues. However, their role in the bone anabolic response remains controversial. We hypothesized that spatial alignment of periosteal nerves with sites of load-induced bone formation would clarify this relationship. To achieve this, we developed RadialQuant, a custom tool for spatial histomorphometry. Tibiae of control and neurectomized (sciatic/femoral nerve cut) pan-neuronal Baf53b-tdTomato reporter mice were loaded for 5 days. Bone formation and periosteal nerve axon density were then quantified simultaneously in non-decalcified …

Norovirus Co-Opts Ninj1 For Selective Protein Secretion, Jaewon Song, Wandy L Beatty, Anthony Orvedahl, Et Al.

2020-Current year OA Pubs

Plasma membrane rupture by Ninjurin-1 (NINJ1) executes programmed cell death, releasing large cellular damage-associated molecular patterns (DAMPs). However, the regulation and selectivity of NINJ1-mediated DAMP release remain unexplored. Here, we uncover that murine norovirus (MNoV) strategically co-opts NINJ1 to selectively release the intracellular viral protein NS1, while NINJ1-mediated plasma membrane rupture simultaneously bulk-releases various cellular DAMPs. Host caspase-3 cleaves the precursor NS1/2, leading to NS1 secretion via an unconventional pathway. An unbiased CRISPR screen identifies NINJ1 as an essential factor for NS1 secretion. During infection, NINJ1 is recruited to the viral replication site, where it oligomerizes and forms speckled bodies, …

Myelin-Reactive Cd8+ T Cells Influence Conventional Dendritic Cell Subsets Towards A Mature And Regulatory Phenotype In Experimental Autoimmune Encephalomyelitis, Mohit Upadhye, Connor R Wilhelm, Kai J Rogers, Chakrapani Vemulawada, Nicholas Borcherding, Alexander W Boyden, Kevin L Legge, Nitin J Karandikar

2020-Current year OA Pubs

Multiple sclerosis (MS), an autoimmune demyelinating disease of the central nervous system, is modeled in mice as experimental autoimmune encephalomyelitis (EAE). While CD4

Accelerating Earlier Access To Anti-Tnf-Α Agents With Biosimilar Medicines In The Management Of Inflammatory Bowel Disease, Gionata Fiorino, Ashwin Ananthakrishnan, Russell D Cohen, Raymond K Cross, Parakkal Deepak, Francis A Farraye, Jonas Halfvarson, A Hillary Steinhart

2020-Current year OA Pubs

Data indicate that earlier initiation of anti-tumor necrosis factor alpha (anti-TNF-α) biologic medicines may prevent progression to irreversible bowel damage and improve outcomes for patients with inflammatory bowel disease (IBD), particularly Crohn's disease. However, the high cost of such therapies may restrict access and prevent timely treatment of IBD. Biosimilar anti-TNF-α medicines may represent a valuable opportunity for cost savings and optimized patient outcomes by improving access to advanced therapies and allowing earlier anti-TNF-α treatment initiation. Biosimilar anti-TNF-α medicines have been shown to offer consistent therapeutic outcomes to their reference medicines, yet despite entering the IBD treatment armamentarium over 10 …

Developing Evaluation Metrics To Measure The Us National Institute Of Health Plans To Enhance Diverse Perspectives: A Protocol For A Consensus-Based Study, Yulia A Levites Strekalova, Sanjay Jain, Pinaki Sarder

2020-Current year OA Pubs

INTRODUCTION: The diversity of participating investigators representing diverse disciplines, career stages, stakeholder groups, regions and types of institutions is essential for the success of large-scale research programmes. In 2021, the National Institutes of Health introduced a requirement for some of its large grants to include a separate section that describes the project's plan for enhancing diverse perspectives (PEDPs). Our project aims to develop consensus-based PEDP evaluation metrics and instruments that can be systematically and sustainably collected across the projects.

METHODS AND ANALYSIS: Evaluation work is organised into three objectives. First, shared knowledge about PEDP infrastructures, activities and outcomes will be …

The Hao-Fountain Syndrome Protein Usp7 Regulates Neuronal Connectivity In The Brain Via A Novel P53-Independent Ubiquitin Signaling Pathway, Hao Chen, Cole J Ferguson, Dylan C Mitchell, Isabel Risch, Amanda Titus, Joao A Paulo, Andrew Hwang, Loren K Beck, Tsen-Hsuan Lin, Sheng-Kwei Song, Carla M Yuede, Hiroko Yano, Obi L Griffith, Malachi Griffith, Steven P Gygi, Azad Bonni, Albert H Kim, Et Al.

2020-Current year OA Pubs

Mutation or deletion of the deubiquitinase USP7 causes Hao-Fountain syndrome (HAFOUS), which is characterized by speech delay, intellectual disability, and aggressive behavior and highlights important unknown roles of USP7 in the nervous system. Here, we conditionally delete USP7 in glutamatergic neurons in the mouse forebrain, triggering disease-relevant phenotypes, including sensorimotor deficits, impaired cognition, and aggressive behavior. Although USP7 deletion induces p53-dependent neuronal apoptosis, most behavioral abnormalities in USP7 conditional knockout mice persist following p53 loss. Strikingly, USP7 deletion perturbs the synaptic proteome and dendritic spinogenesis independent of p53. Integrated proteomics and biochemical analyses identify the RNA splicing factor Ppil4 as …

Phospho-Relay Feedback Loops Control Egress Vs. Intracellular Development In Toxoplasma Gondii, Ja E Claywell, Yong Fu, L David Sibley

2020-Current year OA Pubs

The intracellular parasite Toxoplasma gondii alternates between a motile invasive and a quiescent intracellular replicative form, yet how these transitions are regulated is unknown. A positive feedback loop involving protein kinase G (PKG) and calcium-dependent PKs (CDPKs) controls motility, invasion, and egress by Toxoplasma gondii, while PKA isoform c1 (PKAc1) counteracts this pathway. Shortly after invasion, PKAc1 is activated by cyclic AMP (cAMP) produced by adenylate cyclases, leading to the suppression of the PKG/CDPK pathway. PKAc1 further activates phosphodiesterase 2, which selectively consumes cAMP, thus forming a negative feedback loop, causing transient activation of PKAc1. Perturbation of cyclic GMP (cGMP) …

The Spatial Landscape Of Cancer Hallmarks Reveals Patterns Of Tumor Ecological Dynamics And Drug Sensitivity, Mustafa Sibai, Chia-Kuei Mo, Li Ding, Et Al.

2020-Current year OA Pubs

Tumors are complex ecosystems of interacting cell types. The concept of cancer hallmarks distills this complexity into underlying principles that govern tumor growth. Here, we explore the spatial distribution of cancer hallmarks across 63 primary untreated tumors from 10 cancer types using spatial transcriptomics. We show that hallmark activity is spatially organized, with the cancer compartment contributing to the activity of seven out of 13 hallmarks, while the tumor microenvironment (TME) contributes to the activity of the rest. Additionally, we discover that genomic distance between tumor subclones correlates with differences in hallmark activity, even leading to clone-hallmark specialization. Finally, we …

Strategies, Personnel, And Diversity Of Pediatric Antimicrobial Stewardship Programs In The United States: Strategies And Composition Of Us Pediatric Asps, Christina S Manice, Alexander S Plattner, Edan Leshem, Jason G Newland, Mari M Nakamura

2020-Current year OA Pubs

OBJECTIVE: We sought to characterize US pediatric antimicrobial stewardship programs (ASPs), including their hospital demographics, staffing, funded full-time equivalents (FTEs) by hospital size, and relative emphasis on recommended stewardship strategies. We examined the self-reported characteristics of ASP personnel with regard to discipline, race, ethnicity, gender identity, and years of experience in antimicrobial stewardship.

DESIGN: Descriptive two-part survey.

SETTING: Pediatric ASPs at hospitals participating in Sharing Antimicrobial Reports for Pediatric Stewardship (SHARPS), a pediatric quality improvement collaborative of >70 children's hospitals.

PARTICIPANTS: Survey distributed to 82 US pediatric ASPs, excluding hospitals without pediatric ASPs. Part I completed by ASP leader (physician …

Agouti And Bmp Signaling Drive A Naturally Occurring Fate Conversion Of Melanophores To Leucophores In Zebrafish, Delai Huang, Emaan H. Kapadia, Yipeng Liang, Leah P. Shriver, Shengkun Dai, Gary J. Patti, Bruno M. Humbel, Vincent Laudet, David M. Parichy

2020-Current year OA Pubs

No abstract provided.

Epidemiology And Genetic Determination Of Measures Of Peripheral Vascular Health In The Long Life Family Study, Deidra R Fricke, Ryan K Cvejkus, Emma Barinas-Mitchell, Mary F Feitosa, Joanne M Murabito, Sandeep Acharya, Michael R Brent, E Warwick Daw, Ryan L Minster, Joseph M Zmuda, Allison L Kuipers

2020-Current year OA Pubs

Peripheral artery disease (PAD) is a major contributor to morbidity in older adults. We aimed to determine genetic and non-genetic determinants of PAD and ankle-brachial index (ABI) in the Long Life Family Study (LLFS). 3006 individuals had ABI assessment, including 1090 probands (mean age 89), 1554 offspring (mean age 60) and 362 spousal controls (mean age 61). Outcomes include minimum of right and left ABIs and PAD (ABI <0.9). Stepwise regression determined independent significant non-genetic correlates of ABI and PAD. Genomewide association and linkage analyses were adjusted for age, sex, study center, significant principal components, and independent predictors. All analyses accounted for familial relatedness. Median ABI was 1.16 and 7.4% had PAD (18.2% probands, 1.0% offspring, 1.9% controls). Correlates of PAD and lower ABI included age, SBP, and creatinine (ABI only); BMI (ABI only), HDL (ABI only) and DBP (PAD only); and antihypertensive use, current smoking, female sex (ABI only), and high school noncompletion (ABI only). Genomewide linkage identified 1 region (15q12-q13) and association identified 3 single nucleotide polymorphisms (rs780213, rs12512857, rs79644420) of interest. In these families, PAD prevalence was low compared to other studies of older adults. We identified four genomic sites that may harbor variants associated with protection from PAD.

Impact Of Prior Car T-Cell Therapy On Mosunetuzumab Efficacy In Patients With Relapsed Or Refractory B-Cell Lymphomas, Elise A Chong, Nancy L Bartlett, Et Al.

2020-Current year OA Pubs

Mosunetuzumab and other CD20/CD3 bispecific antibodies (BsAbs) have efficacy in B-cell lymphomas relapsing after or refractory to CD19-directed chimeric antigen receptor (CAR)-modified T cells (CAR-T). The optimal timing of BsAbs and biomarkers of BsAb response after CAR-T are unknown. We addressed these questions using clinical data and blood samples from patients previously treated with CAR-T and subsequently treated on a phase 1/2 study of mosunetuzumab. Thirty patients had paired samples at baseline and after 1 cycle of mosunetuzumab. The median time from CAR-T to mosunetuzumab was significantly longer for responding than for nonresponding patients (P = .006, unadjusted for multiple …

Atp-Sensitive Potassium Channels Alter Glycolytic Flux To Modulate Cortical Activity And Sleep, Nicholas J Constantino, Caitlin M Carroll, Holden C Williams, Hemendra J Vekaria, Carla M Yuede, Kai Saito, Patrick W Sheehan, J Andy Snipes, Marcus E Raichle, Erik S Musiek, Patrick G Sullivan, Josh M Morganti, Lance A Johnson, Shannon L Macauley

2020-Current year OA Pubs

Metabolism plays a key role in the maintenance of sleep/wake states. Brain lactate fluctuations are a biomarker of sleep/wake transitions, where increased interstitial fluid (ISF) lactate levels are associated with wakefulness and decreased ISF lactate is required for sleep. ATP-sensitive potassium (K

Tifab Modulates Metabolic Pathways In Kmt2a::Mllt3-Induced Aml Through Hnf4a, Yang Wang, Yan Xiu, Qianze Dong, Jinming Zhao, Kelao Neumbo, Masaru Miyagi, Nicholas Borcherding, Lin Fu, Havana De Celis, Nicolas Pintozzi, Daniel T Starczynowski, Chen Zhao

2020-Current year OA Pubs

Tumor necrosis factor (TNF) receptor-associated factor (TRAF)-interacting protein with forkhead-associated domain B (TIFAB), an inhibitor of NF-κB signaling, plays critical roles in hematopoiesis, myelodysplastic neoplasms, and leukemia. We previously demonstrated that Tifab enhances KMT2A::MLLT3-driven acute myeloid leukemia (AML) by either upregulating Hoxa9 or through ubiquitin-specific peptidase 15-mediated downregulation of p53 signaling. In this study, we show that Tifab deletion in KMT2A::MLLT3-induced AML impairs leukemia stem/progenitor cell (LSPC) engraftment, glucose uptake, and mitochondrial function. Gene set enrichment analysis reveals that Tifab deletion downregulates MYC, HOXA9/MEIS1, mTORC1 signaling, and genes involved in glycolysis and oxidative phosphorylation. By comparing genes upregulated in TIFAB-overexpressing …

Plant-Based, Fast-Food, Western-Contemporary, And Animal-Based Dietary Patterns And Risk Of Premature Aging In Adult Survivors Of Childhood Cancer: A Cross-Sectional Study, Tuo Lan, Mei Wang, Annalynn M Williams, Matthew J Ehrhardt, Jennifer Q Lanctot, Shu Jiang, Kevin R Krull, Gregory T Armstrong, Melissa M Hudson, Graham A Colditz, Leslie L Robison, Kirsten K Ness, Yikyung Park

2020-Current year OA Pubs

BACKGROUND: Although premature aging is a significant concern in adult survivors of childhood cancer, little is known about the role of diet in premature aging in this vulnerable population. Therefore, we examined whether dietary patterns specific to childhood cancer survivors are associated with premature aging.

METHODS: This cross-sectional study included 2904 adult survivors of childhood cancer (mean age = 31 years, SD = 8 years) in the St. Jude Lifetime Cohort. Diet was assessed using a food frequency. Four dietary patterns were identified: (1) plant-based diet pattern high in whole grains, fruit, and vegetables; (2) fast-food diet pattern high in …

Virologic Effects Of Broadly Neutralizing Antibodies Vrc01ls And Vrc07-523ls On Chronic Hiv-1 Infection, Myra Happe, Rachel M. Presti, Et Al.

2020-Current year OA Pubs

BACKGROUNDHIV-1-specific broadly neutralizing monoclonal antibodies (bNAbs) have emerged as promising interventions with the potential to effectively treat and prevent HIV-1 infections. We conducted a phase I clinical trial evaluating the potent CD4-binding site-specific (CD4bs-specific) bNAbs VRC01LS and VRC07-523LS in people with HIV-1 (PWH) not receiving antiretroviral therapy (ART).METHODSParticipants received a single intravenous 40 mg/kg dose of either VRC01LS (n = 7) or VRC07-523LS (n = 9) and did not initiate ART for a minimum of 14 days. The primary study objective was to evaluate safety and tolerability; the secondary study objectives were to evaluate pharmacokinetics (PK) and the impact of …

Improving Cancer Prevention And Control Through Implementing Academic-Local Public Health Department Partnerships - Protocol For A Cluster-Randomized Implementation Trial Using A Positive Deviance Approach, Stephanie Mazzucca-Ragan, Peg Allen, Kathleen Amos, Abigail R Barker, Madisen Brewer, Paul C Erwin, Jessica Gannon, Feng Gao, Rebekah R Jacob, Rebecca Lengnick-Hall, Ross C Brownson

2020-Current year OA Pubs

BACKGROUND: Local public health departments in the United States are responsible for implementing cancer-related programs and policies in their communities; however, many staff have not been trained to use evidence-based processes, and the organizational climate may be unsupportive of evidence-based processes. A promising approach to address these gaps is through academic-public health department (AHD) partnerships, in which practitioners and academics collaborate to improve public health practice and education through joint research projects and educational opportunities. Prior research has demonstrated the benefits of AHD partnerships to public health practice and education. However, knowledge about how AHD partnerships should be structured to …

Healthcare Facility Readiness And Availability For Hypertension And Type 2 Diabetes Care In Puno, Peru: A Cross-Sectional Survey Of Healthcare Facilities, Katherine E Lord, Parker K Acevedo, Lindsay J Underhill, Gonzalo Cuentas, Sonia Paredes, Juan C Mendoza, Percy Herrera, Victoria B Chou, Victor G Dávila-Román, Stella M Hartinger, William Checkley

2020-Current year OA Pubs

BACKGROUND: Non-communicable diseases are a rapidly growing cause of mortality and morbidity in Peru, accounting for 73% of total deaths. There is limited research on health system readiness to manage this rising burden. Our study characterized the readiness of healthcare facilities to manage patients with hypertension and/or type 2 diabetes (T2D) across two public healthcare systems in Puno, a largely rural and low-income department in Peru.

METHODS: We adapted the World Health Organization Service Availability and Readiness Assessment to characterize resources and services for hypertension and T2D care. We administered the survey to personnel at healthcare facilities in Puno. Service …

Female Mice Lacking Glua3 Show Early Onset Of Hearing Loss, Cochlear Synaptopathy, And Afferent Terminal Swellings In Ambient Sound Levels, Indra Pal, Atri Bhattacharyya, Babak V-Ghaffari, Essence Devine Williams, Maolei Xiao, Mark Allen Rutherford, María Eulalia Rubio

2020-Current year OA Pubs

AMPA-type glutamate receptors (AMPARs) mediate excitatory cochlear transmission. However, unique roles of AMPAR subunits are unresolved. Lack of subunit GluA3 (

Impact Of Biocontainment On Small Animal Pet Performance Adapted For Bsl-2/3 Infectious Disease Imaging Research, Isabella Salerno, Nadia Benabdallah, Amanda Fears, Ryan Unnerstall, Lindsey Hauck, Sergey Komarov, Linda Cox, Hanwen Zhang, Kevin Poenicke, Joseph Aromando, Yuan-Chun Tai, Timothy Wencewicz, Deborah J Veis, Daniel L J Thorek

2020-Current year OA Pubs

BACKGROUND: Biocontainment protocols are critical for conducting infectious disease (ID) research, particularly when using small animal models in biosafety level (BSL) 2/3 environments. This study evaluates the impact of poly-methyl methacrylate (PMMA) containment vessels on the performance of preclinical positron emission tomography (PET) systems. We tested containment vessels designed with varying wall thicknesses (3, 6, and 9 mm) to simulate ID imaging facility equipment and protocols. Through the use of multicomponent phantoms and in vivo mouse models of Staphylococcus aureus infection, we assessed key performance metrics including count rate, image quality, activity recovery, and spatial resolution.

RESULTS: The results indicate …

Progression Of Otologic And Nasal Symptoms In Primary Ciliary Dyskinesia Throughout Childhood, Isabelle Dagher, Adam J Kimple, Thomas W Ferkol, Scott D Sagel, Sharon D Dell, Carlos E Milla, Lang Li, Feng-Chang Lin, Kelli M Sullivan, Maimoona A Zariwala, Michael R Knowles, Margaret Rosenfeld, Margaret W Leigh, Stephanie D Davis, Genetic Disorders Of Mucociliary Clearance Consortium

2020-Current year OA Pubs

OBJECTIVE: Primary ciliary dyskinesia (PCD) is characterized by upper and lower airway disease. Multiple studies have demonstrated the progression of pulmonary disease; however, longitudinal changes in the otologic and nasal symptoms have not been well described in patients. This study defines age-related prevalence, age of onset, and age-related trends in self-reported otologic and sinonasal comorbidities in individuals with PCD.

STUDY DESIGN: A prospective, longitudinal, multicenter, observational study spanning up to 12 years.

SETTING: Six PCD centers in North America.

METHODS: Inclusion criteria were < 19 years of age and a confirmed diagnosis of PCD based on electron microscopy and/or genetics. A standardized medical history questionnaire and physical exam were completed during each study visit. Descriptive statistics were performed for the entire cohort as well as for subgroups based on ciliary ultrastructure.

RESULTS: A total of 147 participants were followed for an average of 7.6 ± 3.2 years. Pressure …