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Markers Of Early Changes In Cognition Across Cohorts Of Adults With Down Syndrome At Risk Of Alzheimer's Disease, Andrew J Aschenbrenner, Jason Hassenstab, Et Al

Open Access Publications

Introduction: Down syndrome (DS), a genetic variant of early onset Alzheimer's disease (AD), lacks a suitable outcome measure for prevention trials targeting pre-dementia stages.

Methods: We used cognitive test data collected in several longitudinal aging studies internationally from 312 participants with DS without dementia to identify composites that were sensitive to change over time. We then conducted additional analyses to provide support for the utility of the composites. The composites were presented to an expert panel to determine the most optimal cognitive battery based on predetermined criteria.

Results: There were common cognitive domains across site composites, which were sensitive to …

Distinct Microrna Profiles In The Perilymph And Serum Of Patients With Menière's Disease, Matthew Shew, Helena Wichova, Madeleine St Peter, Athanasia Warnecke, Hinrich Staecker

Open Access Publications

No abstract provided.

A Real-World, Prospective, Multicenter, Single-Arm Observational Study Of Duloxetine In Patients With Major Depressive Disorder Or Generalized Anxiety Disorder, Gyorgy Szekeres, Sandor Rozsa, Peter Dome, Gabor Barsony, Xenia Gonda

Open Access Publications

No abstract provided.

Maturation Of Heterogeneity In Afferent Synapse Ultrastructure In The Mouse Cochlea, Shelby A Payne, Matthew S Joens, Heather Chung, Natalie Skigen, Adam Frank, Sonali Gattani, Kya Vaughn, Allison Schwed, Matt Nester, Atri Bhattacharyya, Guhan Iyer, Bethany Davis, Jason Carlquist, Honey Patel, James A J Fitzpatrick, Mark A Rutherford

Open Access Publications

Auditory nerve fibers (ANFs) innervating the same inner hair cell (IHC) may have identical frequency tuning but different sound response properties. In cat and guinea pig, ANF response properties correlate with afferent synapse morphology and position on the IHC, suggesting a causal structure-function relationship. In mice, this relationship has not been fully characterized. Here we measured the emergence of synaptic morphological heterogeneities during maturation of the C57BL/6J mouse cochlea by comparing postnatal day 17 (p17, ∼3 days after hearing onset) with p34, when the mouse cochlea is mature. Using serial block face scanning electron microscopy and three-dimensional reconstruction we measured …

Infiltration By Cxcl10 Secreting Macrophages Is Associated With Antitumor Immunity And Response To Therapy In Ovarian Cancer Subtypes, Laura Ardighieri, William Vermi, Et Al

Open Access Publications

Ovarian carcinomas (OCs) are poorly immunogenic and immune checkpoint inhibitors (ICIs) have offered a modest benefit. In this study, high CD3

Inhibition Of Discoidin Domain Receptors By Imatinib Prevented Pancreatic Fibrosis Demonstrated In Experimental Chronic Pancreatitis Model, Sapana Bansod, Mohd Aslam Saifi, Chandraiah Godugu

Open Access Publications

No abstract provided.

Outcome After Acute Ischemic Stroke Is Linked To Sex-Specific Lesion Patterns, Anna K. Bonkhoff, Laura Heitsch, Chia-Ling Phuah, Et Al

Open Access Publications

No abstract provided.

The Sulfur Microbial Diet And Risk Of Colorectal Cancer By Molecular Subtypes And Intratumoral Microbial Species In Adult Men, Daniel R. Sikavi, Yin Cao, Et Al

Open Access Publications

No abstract provided.

Assessing The Post‑Treatment Therapeutic Effect Of Pinaverium In Irritable Bowel Syndrome: A Randomized Controlled Trial, Liang Zheng, Qi Xiao, Et Al

Open Access Publications

No abstract provided.

Pediatric Antimicrobial Stewardship Practices At Discharge: A National Survey, Marie E Wang, Kimberly Felder, Jason G Newland, Adam L Hersh, Nipunie S Rajapakse, Zachary I Willis, Ritu Banerjee, Jeffrey S Gerber, Hayden T Schwenk, Louise E Vaz

Open Access Publications

We surveyed pediatric antimicrobial stewardship program (ASP) site leaders within the Sharing Antimicrobial Reports for Pediatric Stewardship collaborative regarding discharge stewardship practices. Among 67 sites, 13 (19%) reported ASP review of discharge antimicrobial prescriptions. These findings highlight discharge stewardship as a potential opportunity for improvement during the hospital-to-home transition.

Multisociety Statement On Coronavirus Disease 2019 (Covid-19) Vaccination As A Condition Of Employment For Healthcare Personnel, David J Weber, Hilary M Babcock, Et Al

Open Access Publications

This consensus statement by the Society for Healthcare Epidemiology of America (SHEA) and the Society for Post-Acute and Long-Term Care Medicine (AMDA), the Association for Professionals in Epidemiology and Infection Control (APIC), the HIV Medicine Association (HIVMA), the Infectious Diseases Society of America (IDSA), the Pediatric Infectious Diseases Society (PIDS), and the Society of Infectious Diseases Pharmacists (SIDP) recommends that coronavirus disease 2019 (COVID-19) vaccination should be a condition of employment for all healthcare personnel in facilities in the United States. Exemptions from this policy apply to those with medical contraindications to all COVID-19 vaccines available in the United States …

Site Selective C–H Functionalization Of Mitragyna Alkaloids Reveals A Molecular Switch For Tuning Opioid Receptor Signaling Efficacy, Srijita Bhowmik, Juraj Galeta, Václav Havel, Melissa Nelson, Abdelfattah Faouzi, Benjamin Bechand, Mike Ansonoff, Tomas Fiala, Amanda Hunkele, Andrew C. Kruegel, John E. Pintar, Susruta Majumdar, Jonathan A. Javitch, Dalibor Sames

Open Access Publications

No abstract provided.

Untargeted Metabolomics And Infrared Ion Spectroscopy Identify Biomarkers For Pyridoxine-Dependent Epilepsy, Udo Fh Engelke, Laura A Jansen, Et Al

Open Access Publications

BackgroundPyridoxine-dependent epilepsy (PDE-ALDH7A1) is an inborn error of lysine catabolism that presents with refractory epilepsy in newborns. Biallelic ALDH7A1 variants lead to deficiency of α-aminoadipic semialdehyde dehydrogenase/antiquitin, resulting in accumulation of piperideine-6-carboxylate (P6C), and secondary deficiency of the important cofactor pyridoxal-5'-phosphate (PLP, active vitamin B6) through its complexation with P6C. Vitamin B6 supplementation resolves epilepsy in patients, but intellectual disability may still develop. Early diagnosis and treatment, preferably based on newborn screening, could optimize long-term clinical outcome. However, no suitable PDE-ALDH7A1 newborn screening biomarkers are currently available.MethodsWe combined the innovative analytical methods untargeted metabolomics and infrared ion spectroscopy to discover …

Dysregulation Of Mannose-6-Phosphate-Dependent Cholesterol Homeostasis In Acinar Cells Mediates Pancreatitis, Olga A Mareninova, Yan Xie, Nicholas O Davidson, Et Al

Open Access Publications

Disordered lysosomal/autophagy pathways initiate and drive pancreatitis, but the underlying mechanisms and links to disease pathology are poorly understood. Here, we show that the mannose-6-phosphate (M6P) pathway of hydrolase delivery to lysosomes critically regulates pancreatic acinar cell cholesterol metabolism. Ablation of the Gnptab gene encoding a key enzyme in the M6P pathway disrupted acinar cell cholesterol turnover, causing accumulation of nonesterified cholesterol in lysosomes/autolysosomes, its depletion in the plasma membrane, and upregulation of cholesterol synthesis and uptake. We found similar dysregulation of acinar cell cholesterol, and a decrease in GNPTAB levels, in both WT experimental pancreatitis and human disease. The …

Neurofibrillary Tau Depositions Emerge With Subthreshold Cerebral Beta-Amyloidosis In Down Syndrome, Matthew D Zammit, Dana L Tudorascu, Charles M Laymon, Sigan L Hartley, Paul A Ellison, Shahid H Zaman, Beau M Ances, Sterling C Johnson, Charles K Stone, Marwan N Sabbagh, Chester A Mathis, William E Klunk, Ann D Cohen, Benjamin L Handen, Bradley T Christian

Open Access Publications

INTRODUCTION: Adults with Down syndrome are genetically predisposed to develop Alzheimer's disease and accumulate beta-amyloid plaques (Aβ) early in life. While Aβ has been heavily studied in Down syndrome, its relationship with neurofibrillary tau is less understood. The aim of this study was to evaluate neurofibrillary tau deposition in individuals with Down syndrome with varying levels of Aβ burden.

METHODS: A total of 161 adults with Down syndrome (mean age = 39.2 (8.50) years) and 40 healthy, non-Down syndrome sibling controls (43.2 (12.6) years) underwent T1w-MRI, [C-11]PiB and [F-18]AV-1451 PET scans. PET images were converted to units of standardized uptake …

White Matter Integrity Of Contralesional And Transcallosal Tracts May Predict Response To Upper Limb Task-Specific Training In Chronic Stroke, Daniela J S Mattos, Jerrel Rutlin, Xin Hong, Kristina Zinn, Joshua S Shimony, Alexandre R Carter

Open Access Publications

OBJECTIVE: To investigate white matter (WM) plasticity induced by intensive upper limb (UL) task specific training (TST) in chronic stroke.

METHODS: Diffusion tensor imaging data and UL function measured by the Action Research Arm Test (ARAT) were collected in 30 individuals with chronic stroke prior to and after intensive TST. ANOVAs tested the effects of training on the entire sample and on the Responders [ΔARAT ≥ 5.8, N = 13] and Non-Responders [ΔARAT < 5.8, N = 17] groups. Baseline fractional anisotropy (FA) values were correlated with ARATpost TST controlling for baseline ARAT and age to identify voxels predictive of response to TST.

RESULTS: While ARAT scores increased following training (p < 0.0001), FA changes within major WM tracts were not significant at p < 0.05. In the Responder group, larger baseline FA of both contralesional (CL) and transcallosal tracts predicted larger ARAT scores post-TST. Subcortical lesions and more severe damage to transcallosal tracts were more pronounced in the Non-Responder than in the Responder group.

CONCLUSIONS: The motor improvements post-TST in the Responder group may reflect the engagement of interhemispheric processes not available to …

Ex Vivo Porcine Model For Robot-Assisted Partial Nephrectomy Simulation At A High-Volume Tertiary Center: Resident Perception And Validation Assessment Using The Global Evaluative Assessment Of Robotic Skills Tool, Alexander K. Chow, Ryan Wong, Steven Monda, Rohit Bhatt, Kenneth G. Sands, Joel Vetter, Niraj Badhiwala, Angelia Declue, Eric H. Kim, Arjun Sivaraman, Ramakrishna Venkatesh, Robert Sherburne Figenshau, Kefu Du

Open Access Publications

No abstract provided.

Weight And Body Mass Index Change After Switching To Integrase Inhibitors Or Tenofovir Alafenamide Among Women Living With Hiv, Cecile D. Lahiri, Jane O'Halloran, Et Al

Open Access Publications

No abstract provided.

Partitioning Of Gene Expression Among Zebrafsh Photoreceptor Subtypes, Yohey Ogawa, Joseph C. Corbo

Open Access Publications

No abstract provided.

Listeria Exploits Ifitm3 To Suppress Antibacterial Activity In Phagocytes, Joel M. J. Tan, Michael S. Diamond, Et Al

Open Access Publications

No abstract provided.

Multi-Omics Integration Analysis Identifies Novel Genes For Alcoholism With Potential Overlap With Neurodegenerative Diseases, Manav Kapoor, Michael J. Chao, Emma C. Johnson, Gloriia Novikova, Dongbing Lai, Jacquelyn L. Meyers, Jessica Schulman, John I. Nurnberger Jr., Bernice Porjesz, Yunlong Liu, The Collaborative Study On Genetics Of Alcoholism (Coga), Tatiana Foroud, Howard J. Edenberg, Edoardo Marcora, Arpana Agrawal, Alison Goate

Open Access Publications

No abstract provided.

Family Caregiver Problems In Outpatient Palliative Oncology, Jacquelyn J. Benson, Karla T. Washington, Robin L. Kruse, Debra Parker Oliver, Abigail J. Rolbiecki, George Demiris

Open Access Publications

No abstract provided.

Positive Surgical Margins After Robot-Assisted Partial Nephrectomy Predict Long-Term Oncologic Outcomes For Clinically Localized Renal Masses, B. Malik Wahba, Alexander K. Chow, Kefu Du, Kenneth G. Sands, Alethea G. Paradis, Joel M. Vetter, Ramakrishna Venkatesh, Eric H. Kim, Sam B. Bhayani, R. Sherburne Figenshau

Open Access Publications

No abstract provided.

Study To Enhance Understanding Of Stent-Associated Symptoms: Rationale And Study Design, Charles D. Scales Jr., H. Henry Lai, Alana C. Desai, Jodi A. Antonelli, Naim M. Maalouf, Gregory E. Tasian, Peter P. Reese, Michele Curatolo, Kevin Weinfurt, Hussein R. Al-Khalidi, Hunter Wessells, Ziya Kirkali, Jonathan D. Harper, Niddk Urinary Stone Disease Research Network

Open Access Publications

No abstract provided.

Ubib Proteins Regulate Cellular Coq Distribution In Saccharomyces Cerevisiae, Zachary A. Kemmerer, Kyle P. Robinson, Jonathan M. Schmitz, Mateusz Manicki, Brett R. Paulson, Adam Jochem, Paul D. Hutchins, Joshua J. Coon, David J. Pagliarini

Open Access Publications

No abstract provided.

A Ligand-Insensitive Unc5b Splicing Isoform Regulates Angiogenesis By Promoting Apoptosis, David Pradella, William Vermi, Et Al

Open Access Publications

No abstract provided.

Low-Dose Interleukin-2 And Regulatory T Cell Treatments Attenuate Punctate And Dynamic Mechanical Allodynia In A Mouse Model Of Sciatic Nerve Injury, Rong Hu, Jintao Zhang, Xuemei Liu, Dong Huang, Yu-Qing Cao

Open Access Publications

Purpose: Nerve injury-induced mechanical hyper-sensitivity, in particular stroking-induced dynamic allodynia, is highly debilitating and difficult to treat. Previous studies indicate that the immunosuppressive regulatory T (Treg) cells modulate the magnitude of punctate mechanical allodynia resulting from sciatic nerve injury. However, whether enhancing Treg-mediated suppression attenuates dynamic allodynia is not known. In the present study, we addressed this knowledge gap by treating mice with low-dose interleukin-2 (ld-IL2) injections or adoptive transfer of Treg cells.

Methods: Female Swiss Webster mice received daily injections of ld-IL2 (1 μg/mouse, intraperitoneally) either before or after unilateral spared nerve injury (SNI). Male C57BL/6J mice received adoptive …

Association Between Smoking And Molecular Subtypes Of Colorectal Cancer, Xiaoliang Wang, Yin Cao, Et Al

Open Access Publications

Background: Smoking is associated with colorectal cancer (CRC) risk. Previous studies suggested this association may be restricted to certain molecular subtypes of CRC, but large-scale comprehensive analysis is lacking.

Methods: A total of 9789 CRC cases and 11 231 controls of European ancestry from 11 observational studies were included. We harmonized smoking variables across studies and derived sex study-specific quartiles of pack-years of smoking for analysis. Four somatic colorectal tumor markers were assessed individually and in combination, including

Results: Heavier smoking was associated with higher risk of CRC overall and stratified by individual markers (

Conclusion: Smoking was associated with …

Cardiac Performance In The First Year Of Age Among Preterm Infants Fed Maternal Breast Milk, Afif El-Khuffash, Adam J. Lewandowski, Amish Jain, Aaron Hamvas, Gautam K. Singh, Philip T. Levy

Open Access Publications

Importance: There is a beneficial association between human breast milk exposure in the neonatal period and cardiac mechanics in adults who were born preterm. It is unknown whether this benefit is apparent in infants in the first year of age.

Objective: To test the hypothesis that higher consumption of mother's own milk in preterm infants is associated with enhanced cardiac performance during the first year of age.

Design, Setting, and Participants: This cross-sectional study of cardiac and nutritional data at an academic medical center included 80 individuals born preterm and 100 individuals in the control group born full-term. All births …

Closed-Loop Acoustic Stimulation During Sedation With Dexmedetomidine (Class-D): Protocol For A Within-Subject, Crossover, Controlled, Interventional Trial With Healthy Volunteers, Christian S Guay, Alyssa K Labonte, Michael C Montana, Eric C Landsness, Brendan P Lucey, Mohammadmehdi Kafashan, Simon Haroutounian, Michael S Avidan, Emery N Brown, Ben Julian A Palanca

Open Access Publications

Introduction: The relative power of slow-delta oscillations in the electroencephalogram (EEG), termed slow-wave activity (SWA), correlates with level of unconsciousness. Acoustic enhancement of SWA has been reported for sleep states, but it remains unknown if pharmacologically induced SWA can be enhanced using sound. Dexmedetomidine is a sedative whose EEG oscillations resemble those of natural sleep. This pilot study was designed to investigate whether SWA can be enhanced using closed-loop acoustic stimulation during sedation (CLASS) with dexmedetomidine.

Methods: Closed-Loop Acoustic Stimulation during Sedation with Dexmedetomidine (CLASS-D) is a within-subject, crossover, controlled, interventional trial with healthy volunteers. Each participant will be sedated …