Medicine and Health Sciences Commons^™

Corpora Amylacea Are Associated With Tau Burden And Cognitive Status In Alzheimer's Disease, Connor M Wander, Tamy Harumy Moraes Tsujimoto, John F Ervin, Chanung Wang, Spencer M Maranto, Vanya Bhat, Julian D Dallmeier, Shih-Hsiu Jerry Wang, Feng-Chang Lin, William K Scott, David M Holtzman, Todd J Cohen

2020-Current year OA Pubs

Corpora amylacea (CA) and their murine analogs, periodic acid Schiff (PAS) granules, are age-related, carbohydrate-rich structures that serve as waste repositories for aggregated proteins, damaged cellular organelles, and other cellular debris. The structure, morphology, and suspected functions of CA in the brain imply disease relevance. Despite this, the link between CA and age-related neurodegenerative diseases, particularly Alzheimer's disease (AD), remains poorly defined. We performed a neuropathological analysis of mouse PAS granules and human CA and correlated these findings with AD progression. Increased PAS granule density was observed in symptomatic tau transgenic mice and APOE knock-in mice. Using a cohort of …

Discovery And Validation Of Dominantly Inherited Alzheimer's Disease Mutations In Populations From Latin America, Leonel Tadao Takada, Bhagyashri D Burgute, Ellen Ziegemeier, Jennifer Petranek, Carlos Cruchaga, Maria Victoria Fernández, Eric Mcdade, Randall J Bateman, Celeste M Karch, Jorge J Llibre-Guerra, Et Al.

2020-Current year OA Pubs

BACKGROUND: In fewer than 1% of patients, AD is caused by autosomal dominant mutations in either the presenilin 1 (PSEN1), presenilin 2 (PSEN2), or amyloid precursor protein (APP) genes. The full extent of familial AD and frequency of these variants remains understudied in Latin American (LatAm) countries. Due to the rare nature of these variants, determining the pathogenicity of a novel variant in these genes can be challenging. Here, we use a systematic approach to assign the likelihood of pathogenicity in variants from densely affected families in Latin American populations.

METHODS: Clinical data was collected from LatAm families at risk …

Safety And Tolerability Of Carboplatin And Paclitaxel In Cancer Patients With Hiv (Amc-078), An Aids Malignancy Consortium (Amc) Study, Missak Haigentz, Page Moore, Milan Bimali, Timothy Cooley, Joseph Sparano, Michelle Rudek, Lee Ratner, David Henry, Juan Ramos, John Deeken, Paul Rubinstein, Elizabeth Chiao

2020-Current year OA Pubs

BACKGROUND: Persons living with human immunodeficiency virus are an underserved population for evidence-based cancer treatment. Paclitaxel and carboplatin (PCb) is an active regimen against a variety of solid tumors, including several seen in excess in patients with HIV infection. We performed a pilot trial to evaluate the safety of full-dose PCb in people living with human immunodeficiency virus and cancer.

METHODS: Eligible patients, stratified by concurrent antiretroviral therapy (ART) that included CYP3A4 inhibitors or not, received paclitaxel (175 mg/m2) in combination with carboplatin (target AUC 6) intravenously every 3 weeks for up to 6 cycles.

RESULTS: Sixteen evaluable patients received …

Facilitators For Retaining Men Who Have Sex With Men In Pre-Exposure Prophylaxis Care In Real World Clinic Settings Within The United States, Brooke G Rogers, R R Patel, K Curoe, A Underwood, J Villalobos, Et Al.

2020-Current year OA Pubs

BACKGROUND: Pre-exposure prophylaxis (PrEP) can significantly reduce HIV acquisition especially among communities with high HIV prevalence, including men who have sex with men (MSM). Much research has been finding suboptimal PrEP persistence; however, few studies examine factors that enhance PrEP persistence in real-world settings.

METHODS: We interviewed 33 patients who identified as MSM at three different PrEP clinics in three regions of the U.S. (Northeast, South, Midwest). Participants were eligible if they took PrEP and had been retained in care for a minimum of 6 months. Interviews explored social, structural, clinic-level and behavioral factors that influencing PrEP persistence.

RESULTS: Through …

Developmental Trajectories Of Cortical Thickness By Functional Brain Network: The Roles Of Pubertal Timing And Socioeconomic Status, Ashley F. P. Sanders, Graham L. Baum, Michael P. Harms, Sridhar Kandala, Susan Y. Bookheimer, Mirella Dapretto, Leah H. Somerville, Kathleen M. Thomas, David C. Van Essen, Essa Yacoub, Deanna M Barch

2020-Current year OA Pubs

The human cerebral cortex undergoes considerable changes during development, with cortical maturation patterns reflecting regional heterogeneity that generally progresses in a posterior-to-anterior fashion. However, the organizing principles that govern cortical development remain unclear. In the current study, we characterized age-related differences in cortical thickness (CT) as a function of sex, pubertal timing, and two dissociable indices of socioeconomic status (i.e., income-to-needs and maternal education) in the context of functional brain network organization, using a cross-sectional sample (n = 789) diverse in race, ethnicity, and socioeconomic status from the Lifespan Human Connectome Project in Development (HCP-D). We found that CT generally …

Psychiatry Training In Autism Spectrum Disorder And Intellectual Disability: Ongoing Gaps And Emerging Opportunities, Natasha Marrus, Kathleen A. Koth, Jessica A. Hellings, Rachel Mcdonald, Mcleod Frampton Gwynette, Rebecca Muhle, William D. Lohr, Roma A. Vasa

2020-Current year OA Pubs

Children, adolescents, and adults with autism spectrum disorder and intellectual disability experience high rates of co-occurring psychiatric conditions throughout their lifetime. However, there is a shortage of psychiatrists to treat these populations. We evaluated how much education psychiatrists-in-training receive on how to care for individuals with autism spectrum disorder/intellectual disability. We found that in many psychiatry programs, residents receive limited training experiences in autism spectrum disorder/intellectual disability involving lectures and patient contact and that psychiatry program directors would benefit from more resources to strengthen education in autism spectrum disorder/intellectual disability.

Hypertension Treatment In Nigeria (Htn) Program: Rationale And Design For A Type 2 Hybrid, Effectiveness, And Implementation Interrupted Time Series Trial, Abigail S Baldridge, Mark D Huffman, Et Al.

2020-Current year OA Pubs

BACKGROUND: Hypertension is the most common cardiovascular disease in Nigeria and contributes to a large non-communicable disease burden. Our aim was to implement and evaluate a large-scale hypertension treatment and control program, adapted from the Kaiser Permanent Northern California and World Health Organization HEARTS models, within public primary healthcare centers in the Federal Capital Territory, Nigeria.

METHODS: A type 2 hybrid, interrupted time series design was used to generate novel information on large-scale implementation and effectiveness of a multi-level hypertension control program within 60 primary healthcare centers in the Federal Capital Territory, Nigeria. During the formative phase, baseline qualitative assessments …

Emergency Department Communication In Persons Living With Dementia And Care Partners: A Scoping Review, Christopher R Carpenter, Jesseca Leggett, David Carr, Michelle Doering, Beth Prusaczyk, Et Al.

2020-Current year OA Pubs

OBJECTIVES: To synthesize published research exploring emergency department (ED) communication strategies and decision-making with persons living with dementia (PLWD) and their care partners as the basis for a multistakeholder consensus conference to prioritize future research.

DESIGN: Systematic scoping review.

SETTINGS AND PARTICIPANTS: PLWD and their care partners in the ED setting.

METHODS: Informed by 2 Patient-Intervention-Comparison-Outcome (PICO) questions, we conducted systematic electronic searches of medical research databases for relevant publications following standardized methodological guidelines. The results were presented to interdisciplinary stakeholders, including dementia researchers, clinicians, PLWD, care partners, and advocacy organizations. The PICO questions included: How does communication differ for …

Factors Associated With Initiation And Continuation Of Endocrine Therapy In Women With Hormone Receptor-Positive Breast Cancer, Beomyoung Cho, Maria Pérez, Donna B Jeffe, Matthew W Kreuter, Julie A Margenthaler, Graham A Colditz, Ying Liu

2020-Current year OA Pubs

BACKGROUND: Despite benefits of endocrine therapy (ET) for patients with hormone-receptor (HR)-positive breast cancer, many patients do not initiate or discontinue ET against recommendations.

METHODS: We identified variables associated with ET initiation and continuation, analyzing pooled data from two longitudinal studies at a National Cancer Institute comprehensive cancer center in St. Louis, Missouri. The sample included 533 women with newly diagnosed, non-metastatic, HR-positive breast cancer who completed interviews at enrollment and 6, 12, and 24 months after definitive surgical treatment. Logistic regression models estimated the adjusted odds ratio and 95% confidence interval (aOR [95% CI]) for each of self-reported ET …

Microbiota Regulation Of Viral Infections Through Interferon Signaling, Nurul I. Wirusanti, Megan T. Baldridge, Vanessa C Harris

2020-Current year OA Pubs

The interferon (IFN) response is the major early innate immune response against invading viral pathogens and is even capable of mediating sterilizing antiviral immunity without the support of the adaptive immune system. Cumulative evidence suggests that the gut microbiota can modulate IFN responses, indirectly determining virological outcomes. This review outlines our current knowledge of the interactions between the gut microbiota and IFN responses and dissects the different mechanisms by which the gut microbiota may alter IFN expression to diverse viral infections. This knowledge offers a basis for translating experimental evidence from animal studies into the human context and identifies avenues …

Detection Of Brain Tau Pathology In Down Syndrome Using Plasma Biomarkers, Shorena Janelidze, Bradley T Christian, Julie Price, Charles Laymon, Nicole Schupf, William E Klunk, Ira Lott, Wayne Silverman, H Diana Rosas, Shahid Zaman, Mark Mapstone, Florence Lai, Beau M Ances, Benjamin L Handen, Oskar Hansson

2020-Current year OA Pubs

IMPORTANCE: Novel plasma biomarkers, especially phosphorylated tau (p-tau), can detect brain tau aggregates in Alzheimer disease.

OBJECTIVE: To determine which plasma biomarker combinations can accurately detect tau pathological brain changes in Down syndrome (DS).

DESIGN, SETTING, AND PARTICIPANTS: The cross-sectional, multicenter Alzheimer's Biomarker Consortium-Down Syndrome study included adults with DS and a control group of siblings without DS. All participants with plasma, positron emission tomography (PET), and cognitive measures available by the time of data freeze 1.0 were included. Participants were enrolled between 2016 and 2019, and data were analyzed from August 2021 to April 2022.

EXPOSURES: Plasma p-tau217, glial …

Predicting Brain Age From Functional Connectivity In Symptomatic And Preclinical Alzheimer Disease, Peter R. Millar, Patrick H. Luckett, Brian A. Gordon, Tammie L. S. Benzinger, Suzanne E. Schindler, Anne M. Fagan, Carlos Cruchaga, Randall J. Bateman, Ricardo Allegri, Mathias Jucker, Jae-Hong Lee, Hiroshi Mori, Stephen P. Salloway, Igor Yakushev, John C. Morris, Beau M. Ances, Dominantly Inherited Alzheimer Network

2020-Current year OA Pubs

"Brain-predicted age" quantifies apparent brain age compared to normative neuroimaging trajectories. Advanced brain-predicted age has been well established in symptomatic Alzheimer disease (AD), but is underexplored in preclinical AD. Prior brain-predicted age studies have typically used structural MRI, but resting-state functional connectivity (FC) remains underexplored. Our model predicted age from FC in 391 cognitively normal, amyloid-negative controls (ages 18-89). We applied the trained model to 145 amyloid-negative, 151 preclinical AD, and 156 symptomatic AD participants to test group differences. The model accurately predicted age in the training set. FC-predicted brain age gaps (FC-BAG) were significantly older in symptomatic AD and …

Mass Drug Administration Of Ivermectin, Diethylcarbamazine, Plus Albendazole Compared With Diethylcarbamazine Plus Albendazole For Reduction Of Lymphatic Filariasis Endemicity In Papua New Guinea: A Cluster-Randomised Trial, Moses Laman, Gary J Weil, Et Al.

2020-Current year OA Pubs

BACKGROUND: A single co-administered dose of a triple-drug regimen (ivermectin, diethylcarbamazine, and albendazole) has been shown to be safe and more efficacious for clearing Wuchereria bancrofti microfilariae than the standard two-drug regimen of diethylcarbamazine plus albendazole in clinical trials. However, the effectiveness of mass drug administration with the triple-drug regimen compared with the two-drug regimen is unknown. We compared the effectiveness of mass drug administration with the triple-drug and two-drug regimens for reducing microfilariae prevalence to less than 1% and circulating filarial antigen prevalence to less than 2%, levels that are unlikely to sustain transmission of lymphatic filariasis, in Papua …

Assessment Of Apple Watch Series 6 Pulse Oximetry And Electrocardiograms In A Pediatric Population, Lauren Littell, Lisa Roelle, Aarti Dalal, George F. Van Hare, William B. Orr, Nathan Miller, Jennifer N. Avari Silva

2020-Current year OA Pubs

BACKGROUND: Recent technologic advances have resulted in increased development and utilization of direct-to-consumer cardiac wearable devices with various functionality. This study aimed to assess Apple Watch Series 6 (AW6) pulse oximetry and electrocardiography (ECG) in a cohort of pediatric patients.

METHODS: This single-center, prospective study enrolled pediatric patients ≥ 3kg and having an ECG and/or pulse oximetry (SpO2) as part of their planned evaluation. Exclusion criteria: 1) non-English speaking patients and 2) patients in state custody. Simultaneous tracings were obtained for SpO2 and ECG with concurrent standard pulse oximeter and 12-lead ECG. AW6 automated rhythm interpretations were compared to physician …

Impaired Mitophagy In Sanfilippo A Mice Causes Hypertriglyceridemia And Brown Adipose Tissue Activation, Miguel Tillo, Patricia I Dickson, Et Al.

2020-Current year OA Pubs

Lysosomal storage diseases result in various developmental and physiological complications, including cachexia. To study the causes for the negative energy balance associated with cachexia, we assessed the impact of sulfamidase deficiency and heparan sulfate storage on energy homeostasis and metabolism in a mouse model of type IIIa mucopolysaccharidosis (MPS IIIa, Sanfilippo A syndrome). At 12-weeks of age, MPS IIIa mice exhibited fasting and postprandial hypertriglyceridemia compared with wildtype mice, with a reduction of white and brown adipose tissues. Partitioning of dietary [

Resting-State Functional Connectivity Identifies Individuals And Predicts Age In 8-To-26-Month-Olds, Omid Kardan, Sydney Kaplan, Muriah D. Wheelock, Dominique Meyer, Adam T. Eggebrecht, Christopher D. Smyser, Et Al.

2020-Current year OA Pubs

Resting-state functional connectivity (rsFC) measured with fMRI has been used to characterize functional brain maturation in typically and atypically developing children and adults. However, its reliability and utility for predicting development in infants and toddlers is less well understood. Here, we use fMRI data from the Baby Connectome Project study to measure the reliability and uniqueness of rsFC in infants and toddlers and predict age in this sample (8-to-26 months old; n = 170). We observed medium reliability for within-session infant rsFC in our sample, and found that individual infant and toddler's connectomes were sufficiently distinct for successful functional connectome …

Comparison Of Modern Periacetabular Osteotomy For Hip Dysplasia With Total Hip Arthroplasty For Hip Osteoarthritis-10-Year Outcomes Are Comparable In Young Adult Patients, Frank W Parilla, Serena Freiman, Gail E Pashos, Susan Thapa, John C Clohisy

2020-Current year OA Pubs

Young adult patients with symptomatic acetabular dysplasia and marginal secondary osteoarthritis can be faced with the decision to either undergo periacetabular osteotomy (PAO) to relieve symptoms and slow osteoarthritis progression or wait until progression to more advanced disease and undergo total hip arthroplasty (THA). The decision can be difficult, and contemporary literature to guide these decisions is sparse. Therefore, we retrospectively assessed complication rate, survivorship and patient-reported clinical outcomes [modified Harris Hip score (mHHS), UCLA Activity score] in two, consecutive cohorts of patients aged 18-40 years that underwent either PAO for symptomatic acetabular dysplasia (mean age 28.9 years) or THA …

Peptide-Sirna Nanoparticles Targeting Nf-Κb P50 Mitigate Experimental Abdominal Aortic Aneurysm Progression And Rupture, Huimin Yan, Ying Hu, Antonina Akk, Samuel A Wickline, Hua Pan, Christine T N Pham

2020-Current year OA Pubs

Abdominal aortic aneurysm (AAA) is a progressive vascular condition associated with high risk of mortality if left untreated. AAA is an inflammatory process with excessive local production of extracellular matrix degrading enzymes, leading to dilatation and rupture of the abdominal aorta. We posit that targeting NF-κB, a signaling pathway that controls inflammation, will halt AAA progression and prevent rupture. In an elastase-induced AAA model we observed that NF-κB activation increased progressively post-elastase perfusion. Unexpectedly, we found that AAA progression was marked by predominant nuclear accumulation of the NF-κB p50 subunit at the exclusion of p65. Using the amphipathic peptide p5RHH …

Non-Targeted Metabolomics Of Cooked Cowpea (Vigna Unguiculata) And Pigeon Pea (Cajanus Cajan) From Ghana Using Two Distinct And Complementary Analytical Platforms, Brooke Sayre-Chavez, Bridget Baxter, Corey D Broeckling, María Muñoz-Amatriaín, Mark Manary, Elizabeth P Ryan

2020-Current year OA Pubs

Legumes are global staple foods with multiple human health properties that merit detailed composition analysis in cooked forms. This study analyzed cowpea [

Efficient Genome Editing Achieved Via Plug-And-Play Adenovirus Piggyback Transport Of Cas9/Grna Complex On Viral Capsid Surface, Zhi Hong Lu, Jie Li, Igor P Dmitriev, Elena A Kashentseva, David T Curiel

2020-Current year OA Pubs

The capacity to efficiently deliver the gene-editing enzyme complex to target cells is favored over other forms of gene delivery as it offers one-time hit-and-run gene editing, thus improving precision and safety and reducing potential immunogenicity against edited cells in clinical applications. Here we performed a proof-of-mechanism study and demonstrated that a simian adenoviral vector for DNA delivery can be repurposed as a robust intracellular delivery platform for a functional Cas9/guide RNA (gRNA) complex to recipient cells. In this system, the clinically relevant adenovirus was genetically engineered with a plug-and-display technology based on SpyTag003/SpyCatcher003 coupling chemistry. Under physiological conditions, an …

Slc12a8 In The Lateral Hypothalamus Maintains Energy Metabolism And Skeletal Muscle Functions During Aging, Naoki Ito, Ai Takatsu, Hiromi Ito, Yuka Koike, Kiyoshi Yoshioka, Yasutomi Kamei, Shin-Ichiro Imai

2020-Current year OA Pubs

Sarcopenia and frailty are urgent socio-economic problems worldwide. Here we demonstrate a functional connection between the lateral hypothalamus (LH) and skeletal muscle through Slc12a8, a recently identified nicotinamide mononucleotide transporter, and its relationship to sarcopenia and frailty. Slc12a8-expressing cells are mainly localized in the LH. LH-specific knockdown of Slc12a8 in young mice decreases activity-dependent energy and carbohydrate expenditure and skeletal muscle functions, including muscle mass, muscle force, intramuscular glycolysis, and protein synthesis. LH-specific Slc12a8 knockdown also decreases sympathetic nerve signals at neuromuscular junctions and β2-adrenergic receptors in skeletal muscle, indicating the importance of the LH-sympathetic nerve-β2-adrenergic receptor axis. LH-specific overexpression …

Oilcloth Sessions As An Implementation Strategy: A Qualitative Study In Denmark, Jeanette Wassar Kirk, Nina Þórný Stefánsdóttir, Byron J Powell, Mette Bendtz Lindstroem, Ove Andersen, Tine Tjørnhøj-Thomsen, Per Nilsen

2020-Current year OA Pubs

BACKGROUND: The aim of this study was to explore healthcare professionals, managers, and other key employees' experiences of oilcloth sessions as a strategy when implementing new emergency departments in Denmark, based on their participations in these sessions. The study addresses the importance of securing alignment in implementation strategies. Too often, this does not get enough attention in the literature and in practice. In this study, alignment among components was achieved in an educational implementation strategy called oilcloth sessions.

METHODS: The study is based on participants' observations of 13 oilcloth sessions and follow-up via 53 semi-structured interviews with the board of …

Activation Domains Can Decouple The Mean And Noise Of Gene Expression, Kaiser Loell, Yawei Wu, Max V Staller, Barak Cohen

2020-Current year OA Pubs

Regulatory mechanisms set a gene's average level of expression, but a gene's expression constantly fluctuates around that average. These stochastic fluctuations, or expression noise, play a role in cell-fate transitions, bet hedging in microbes, and the development of chemotherapeutic resistance in cancer. An outstanding question is what regulatory mechanisms contribute to noise. Here, we demonstrate that, for a fixed mean level of expression, strong activation domains (ADs) at low abundance produce high expression noise, while weak ADs at high abundance generate lower expression noise. We conclude that differences in noise can be explained by the interplay between a TF's nuclear …

Metrics To Evaluate Implementation Scientists In The Usa: What Matters Most?, Brenna B Maddox, Mary L Phan, Y Vivian Byeon, Courtney Benjamin Wolk, Rebecca E Stewart, Byron J Powell, Kelsie H Okamura, Melanie Pellecchia, Emily M Becker-Haimes, David A Asch, Rinad S Beidas

2020-Current year OA Pubs

BACKGROUND: Implementation science has grown rapidly as a discipline over the past two decades. An examination of how publication patterns and other scholarly activities of implementation scientists are weighted in the tenure and promotion process is needed given the unique and applied focus of the field.

METHODS: We surveyed implementation scientists (mostly from the USA) to understand their perspectives on the following matters: (1) factors weighted in tenure and promotion for implementation scientists, (2) how important these factors are for success as an implementation scientist, (3) how impact is defined for implementation scientists, (4) top journals in implementation science, and …

17q21.31 Sub-Haplotypes Underlying H1-Associated Risk For Parkinson's Disease Are Associated With Lrrc37a/2 Expression In Astrocytes, Kathryn R Bowles, Celeste M Karch, Et Al.

2020-Current year OA Pubs

BACKGROUND: Parkinson's disease (PD) is genetically associated with the H1 haplotype of the MAPT 17q.21.31 locus, although the causal gene and variants underlying this association have not been identified.

METHODS: To better understand the genetic contribution of this region to PD and to identify novel mechanisms conferring risk for the disease, we fine-mapped the 17q21.31 locus by constructing discrete haplotype blocks from genetic data. We used digital PCR to assess copy number variation associated with PD-associated blocks, and used human brain postmortem RNA-seq data to identify candidate genes that were then further investigated using in vitro models and human brain …

Long-Term Outcomes For Ibrutinib-Rituximab And Chemoimmunotherapy In Cll: Updated Results Of The E1912 Trial, Tait D Shanafelt, Amanda F Cashen, Et Al.

2020-Current year OA Pubs

Herein, we present the long-term follow-up of the randomized E1912 trial comparing the long-term efficacy of ibrutinib-rituximab (IR) therapy to fludarabine, cyclophosphamide, and rituximab (FCR) and describe the tolerability of continuous ibrutinib. The E1912 trial enrolled 529 treatment-naïve patients aged ≤70 years with chronic lymphocytic leukemia (CLL). Patients were randomly assigned (2:1 ratio) to receive IR or 6 cycles of FCR. With a median follow-up of 5.8 years, median progression-free survival (PFS) is superior for IR (hazard ratio [HR], 0.37; P < .001). IR improved PFS relative to FCR in patients with both immunoglobulin heavy chain variable region (IGHV) gene mutated CLL (HR: 0.27; P < .001) and IGHV unmutated CLL (HR: 0.27; P < .001). Among the 354 patients randomized to IR, 214 (60.5%) currently remain on ibrutinib. Among the 138 IR-treated patients who discontinued treatment, 37 (10.5% of patients who started IR) discontinued therapy due to disease progression or death, 77 (21.9% of patients who started IR) discontinued therapy for adverse events (AEs)/complications, and 24 (6.8% of patients who started IR) withdrew for other reasons. Progression was uncommon among patients able to remain on ibrutinib. The median time from ibrutinib discontinuation to disease progression or death among those who discontinued treatment for a reason other than progression was 25 months. Sustained improvement in overall survival (OS) was observed for patients in the IR arm (HR, 0.47; P = .018). In conclusion, IR therapy offers superior PFS relative to FCR in patients with IGHV mutated or unmutated CLL, as well as superior OS. Continuous ibrutinib therapy is tolerated beyond 5 years in the majority of CLL patients. This trial was registered at www.clinicaltrials.gov as #NCT02048813.

De Novo Variants Of Csnk2b Cause A New Intellectual Disability-Craniodigital Syndrome By Disrupting The Canonical Wnt Signaling Pathway, Maria Asif, Marwan Shinawi, Et Al.

2020-Current year OA Pubs

No abstract provided.

Microbial Liberation Of N-Methylserotonin From Orange Fiber In Gnotobiotic Mice And Humans, Nathan D Han, Daniel Webber, Stacey Marion, Michael J Barratt, Andrew C Heath, Et Al.

2020-Current year OA Pubs

Plant fibers in byproduct streams produced by non-harsh food processing methods represent biorepositories of diverse, naturally occurring, and physiologically active biomolecules. To demonstrate one approach for their characterization, mass spectrometry of intestinal contents from gnotobiotic mice, plus in vitro studies, revealed liberation of N-methylserotonin from orange fibers by human gut microbiota members including Bacteroides ovatus. Functional genomic analyses of B. ovatus strains grown under permissive and non-permissive N-methylserotonin "mining" conditions revealed polysaccharide utilization loci that target pectins whose expression correlate with strain-specific liberation of this compound. N-methylserotonin, orally administered to germ-free mice, reduced adiposity, altered liver glycogenesis, shortened gut transit …

Hiv Cure Strategies: Which Ones Are Appropriate For Africa?, Christopher Zaab-Yen Abana, Helena Lamptey, Evelyn Y Bonney, George B Kyei

2020-Current year OA Pubs

Although combination antiretroviral therapy (ART) has reduced mortality and improved lifespan for people living with HIV, it does not provide a cure. Patients must be on ART for the rest of their lives and contend with side effects, unsustainable costs, and the development of drug resistance. A cure for HIV is, therefore, warranted to avoid the limitations of the current therapy and restore full health. However, this cure is difficult to find due to the persistence of latently infected HIV cellular reservoirs during suppressive ART. Approaches to HIV cure being investigated include boosting the host immune system, genetic approaches to …

Mapping The Single-Cell Transcriptomic Response Of Murine Diabetic Kidney Disease To Therapies, Haojia Wu, Romer Gonzalez Villalobos, Xiang Yao, Dermot Reilly, Tao Chen, Matthew Rankin, Eugene Myshkin, Matthew D. Breyer, Benjamin D. Humphreys

2020-Current year OA Pubs

Diabetic kidney disease (DKD) occurs in ∼40% of patients with diabetes and causes kidney failure, cardiovascular disease, and premature death. We analyzed the response of a murine DKD model to five treatment regimens using single-cell RNA sequencing (scRNA-seq). Our atlas of ∼1 million cells revealed a heterogeneous response of all kidney cell types both to DKD and its treatment. Both monotherapy and combination therapies targeted differing cell types and induced distinct and non-overlapping transcriptional changes. The early effects of sodium-glucose cotransporter-2 inhibitors (SGLT2i) on the S1 segment of the proximal tubule suggest that this drug class induces fasting mimicry and …