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Impact Of A 2-Year Trial Of Nutritional Ketosis On Indices Of Cardiovascular Disease Risk In Patients With Type 2 Diabetes, Shaminie J Athinarayanan, Sarah J Hallberg, Amy L Mckenzie, Katharina Lechner, Sarah King, James P Mccarter, Jeff S Volek, Stephen D Phinney, Ronald M Krauss

Open Access Publications

BACKGROUND: We have previously reported that in patients with type 2 diabetes (T2D) consumption of a very low carbohydrate diet capable of inducing nutritional ketosis over 2 years (continuous care intervention, CCI) resulted in improved body weight, glycemic control, and multiple risk factors for cardiovascular disease (CVD) with the exception of an increase in low density lipoprotein cholesterol (LDL-C). In the present study, we report the impact of this intervention on markers of risk for atherosclerotic cardiovascular disease (CVD), with a focus on lipoprotein subfraction particle concentrations as well as carotid-artery intima-media thickness (CIMT).

METHODS: Analyses were performed in patients …

The Key Glycolytic Enzyme Phosphofructokinase Is Involved In Resistance To Antiplasmodial Glycosides, Gillian M Fisher, Simon A Cobbold, Andrew Jezewski, Emma F Carpenter, Megan Arnold, Annie N Cowell, Erick T Tjhin, Kevin J Saliba, Tina S Skinner-Adams, Marcus C S Lee, Audrey Odom John, Elizabeth A Winzeler, Malcolm J Mcconville, Sally-Ann Poulsen, Katherine T Andrews

Open Access Publications

No abstract provided.

Frequency And Risk Factors Of Acute Kidney Injury During Diabetic Ketoacidosis In Children And Association With Neurocognitive Outcomes, Sage R. Myers, Kimberly S. Quayle, Et Al

Open Access Publications

Importance: Acute kidney injury (AKI) occurs commonly during diabetic ketoacidosis (DKA) in children, but the underlying mechanisms and associations are unclear.

Objective: To investigate risk factors for AKI and its association with neurocognitive outcomes in pediatric DKA.

Design, Setting, and Participants: This cohort study was a secondary analysis of data from the Pediatric Emergency Care Applied Research Network Fluid Therapies Under Investigation in DKA Study, a prospective, multicenter, randomized clinical trial comparing fluid protocols for pediatric DKA in 13 US hospitals. Included DKA episodes occurred among children age younger than 18 years with blood glucose 300 mg/dL or greater and …

Stem Cell And Niche Regulation In Human Short Bowel Syndrome, Vered A Gazit, Elzbieta A Swietlicki, Miranda U Liang, Adam Surti, Raechel Mcdaniel, Mackenzie Geisman, David M Alvarado, Matthew A Ciorba, Grant Bochicchio, Obeid Ilahi, John Kirby, William J Symons, Nicholas O Davidson, Marc S. Levin, Deborah C Rubin

Open Access Publications

Loss of functional small bowel surface area following surgical resection for disorders such as Crohn's disease, intestinal ischemic injury, radiation enteritis, and in children, necrotizing enterocolitis, atresia, and gastroschisis, may result in short bowel syndrome, with attendant high morbidity, mortality, and health care costs in the United States. Following resection, the remaining small bowel epithelium mounts an adaptive response, resulting in increased crypt cell proliferation, increased villus height, increased crypt depth, and enhanced nutrient and electrolyte absorption. Although these morphologic and functional changes are well described in animal models, the adaptive response in humans is less well understood. Clinically the …

Humoral Immune Responses Mediate The Development Of A Restrictive Phenotype Of Chronic Lung Allograft Dysfunction, Keizo Misumi, David S Wheeler, Yoshiro Aoki, Michael P Combs, Russell R Braeuer, Ryuji Higashikubo, Wenjun Li, Daniel Kreisel, Ragini Vittal, Jeffrey Myers, Amir Lagstein, Natalie M Walker, Carol F Farver, Vibha N Lama

Open Access Publications

Understanding the distinct pathogenic mechanisms that culminate in allograft fibrosis and chronic graft failure is key in improving outcomes after solid organ transplantation. Here, we describe an F1 → parent orthotopic lung transplant model of restrictive allograft syndrome (RAS), a particularly fulminant form of chronic lung allograft dysfunction (CLAD), and identify a requisite pathogenic role for humoral immune responses in development of RAS. B6D2F1/J (H2-b/d) donor lungs transplanted into the parent C57BL/6J (H2-b) recipients demonstrated a spectrum of histopathologic changes, ranging from lymphocytic infiltration, fibrinous exudates, and endothelialitis to peribronchial and pleuroparenchymal fibrosis, similar to those noted in the human …

Perspectives On Patient Experience: A National Survey Of Hospitalists, Rafina Khateeb, Angela Keniston, Amber Moore, Christine Hrach, Kimberly A Indovina, Patrick Kneeland, Mark Rudolph, Marisha Burden

Open Access Publications

Despite efforts to improve patient experience (PX), little is known about the perspective of hospitalists regarding PX initiatives and priorities. A survey was distributed to hospitalist groups across the country assessing involvement in PX initiatives and their perceived effectiveness, what PX means to providers, and facilitators/barriers in improving PX. Ninety-nine percent of respondents had encountered some improvement activity around PX. The most prevalent were communication training, group Hospital Consumer Assessment of Healthcare Providers and Systems data, and interdisciplinary bedside rounding. Respondents rated most initiatives a 5 to 6 out of 10 for their effectiveness, with the perception of effectiveness increasing …

Final 5-Year Findings From The Phase 3 Helios Study Of Ibrutinib Plus Bendamustine And Rituximab In Patients With Relapsed/Refractory Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma, Graeme A M Fraser, Nancy L. Bartlett, Et Al

Open Access Publications

No abstract provided.

Positive Information Facilitates Response Inhibition In Older Adults Only When Emotion Is Task-Relevant, Samantha E Williams, Eric J Lenze, Jill D Waring

Open Access Publications

Emotional information is integral to everyday life and impacts a variety of cognitive abilities including response inhibition, a critical skill for maintaining appropriate and flexible behaviour. However, reported effects of emotion on response inhibition are inconsistent in younger adults, and very limited in older adults. Effects of aging are especially relevant because emotion regulation improves with aging despite declining inhibitory control over neutral information. Across three studies, we assessed the impact of emotional facial expressions on response inhibition in younger and older adults while manipulating attention to task stimuli. Emotional faces (versus neutral faces) altered response inhibition only when task …

Prenatal Stress Exposure And Multimodal Assessment Of Amygdala-Medial Prefrontal Cortex Connectivity In Infants, Kathryn L Humphreys, M C Camacho, Marissa C Roth, Elizabeth C Estes

Open Access Publications

Stressful experiences are linked to neurodevelopment. There is growing interest in the role of stress in the connectivity between the amygdala and medial prefrontal cortex (mPFC), a circuit that subserves automatic emotion regulation. However, the specific timing and mechanisms that underlie the association between stress and amygdala-mPFC connectivity are unclear. Many factors, including variations in fetal exposure to maternal stress, appear to affect early developing brain circuitry. However, few studies have examined the associations of stress and amygdala-mPFC connectivity in early life, when the brain is most plastic and sensitive to environmental influence. In this longitudinal pilot study, we characterized …

Rev-Erbα Mediates Complement Expression And Diurnal Regulation Of Microglial Synaptic Phagocytosis, Percy Griffin, Patrick W. Sheehan, Julie M. Dimitry, Chun Guo, Michael F. Kanan, Jiyeon Lee, Jinsong Zhang, Erik S. Musiek

Open Access Publications

The circadian clock regulates various aspects of brain health including microglial and astrocyte activation. Here, we report that deletion of the master clock protein BMAL1 in mice robustly increases expression of complement genes, including

Arginine Kinetics Are Altered In A Pilot Sample Of Adolescents And Young Adults With Barth Syndrome, W Todd Cade, Kathryn L Bohnert, Adam J Bittel, Shaji J Chacko, Bruce W Patterson, Christina A Pacak, Barry J Byrne, Hilary J Vernon, Dominic N Reeds

Open Access Publications

Barth syndrome (BTHS) is a rare, X-linked cardiomyopathy that is characterized by abnormalities in glucose and lipid metabolism, with less known regarding amino acid metabolism. This pilot study characterized whole-body arginine kinetics and found lower arginine rate of appearance into plasma (0.69 ± 0.09 vs. 0.88 ± 0.06 μmol/kgFFM/min,

The Quest For The Optimal Surgical Management Of Tricuspid Valve Endocarditis In The Current Era: A Narrative Review, Francesco Nappi, Cristiano Spadaccio, Christos Mihos, Kasra Shaikhrezai, Christophe Acar, Marc R. Moon

Open Access Publications

Tricuspid valve endocarditis (TVE) is a growing concern with increasing rates and mortality burden. The currently changing etiology, the antibiotic resistance and the raise in iatrogenic causes as with implantable cardiac devices [cardiac implantable electronic device (CIED)], represent a challenge for the management of these patients. The progressively widespread use of CIEDs is adding to the more commonly known intravenous (IV) drug abuse in the list of causes. Treatment strategies include medical therapy alone or surgery. From the surgical standpoint tricuspid valve repair, replacement or the staged procedure of valvectomy as bridge to replacement are available options. Treatment of endocarditis …

A Narrative Review Of The Interpretation Of Guidelines For The Treatment Of Infective Endocarditis, Umberto Benedetto, Sanjeet Singh Avtaar Singh, Cristiano Spadaccio, Marc R. Moon, Francesco Nappi

Open Access Publications

The recommendations of the current guidelines and the position papers of professional societies from the European Society of Cardiology/European Society of Cardiothoracic Surgeons (ESC), the American College of Cardiology/American Heart Association/Society of Thoracic Surgeon (ACC/AHA/STS) and American Association of Thoracic Surgeon (AATS) regarding management of patients with valvular heart endocarditis were updated over the past decade. However, some of the recommendations appear to contradict one another. Given the changing paradigms on how the disease manifests, our aim was to review the respective guidelines and highlight these differences whilst drawing attention to the subsequent studies from which they were derived. In …

A Management Framework For Left Sided Endocarditis: A Narrative Review, Francesco Nappi, Cristiano Spadaccio, Marc R. Moon

Open Access Publications

Left sided endocarditis (LSE) can include the entirety or portion of mitral and/or aortic valve and the structures in their anatomical contiguity and represent a significant portion of emergency surgical activity. Literature and guidelines on the management of LSE relies mainly on observational studies given the difficulty in designing randomized trials in emergency settings. Heart teams (HT) are often called in to difficult decisions on the most appropriate strategy to adopted in case of LSE. Decision-making should take into account the localization and the extension of the infection, patient preoperative status and comorbidities, presence of a previous valve prosthesis and …

Effect Of Ulnar Collateral Ligament Reconstruction On Pitch Accuracy, Velocity, And Movement In Major League Baseball Pitchers, Braden Mcknight, Nathanael D Heckmann, Xiao T Chen, Kevork Hindoyan, J Ryan Hill, Graham Goldbeck, Reza Omid, George F Rick Hatch Iii, Timothy P Charlton

Open Access Publications

Background: Ulnar collateral ligament (UCL) reconstruction is frequently performed on Major League Baseball (MLB) pitchers. Previous studies have investigated the effects of UCL reconstruction on fastball and curveball velocity, but no study to date has evaluated its effect on fastball accuracy or curveball movement among MLB pitchers.

Purpose/Hypothesis: The primary purpose of this study was to determine the effects of UCL reconstruction on fastball accuracy, fastball velocity, and curveball movement in MLB pitchers. Our hypothesis was that MLB pitchers who underwent UCL reconstruction would return to their presurgery fastball velocity, fastball accuracy, and curveball movement. The secondary purpose of this …

Incidence And Survival For Oropharynx And Non-Oropharynx Head And Neck Cancers Among Veterans Living With Hiv, Angela L Mazul, Christine Hartman, Jennifer Kramer, Donna L White, Kathryn Royse, Suchismita Raychaudhury, Vlad Sandulache, Sarah T Ahmed, Peter Richardson, Andrew G Sikora, Elizabeth Chiao

Open Access Publications

BACKGROUND: People living with HIV/AIDS (PLWH) have an excess risk for head and neck squamous cell carcinoma (HNSCC) compared to the general U.S. population, but little is known about HIV-specific risk factors associated with the incidence and outcomes HNSCC. We aim to identify clinical and HIV-specific risk factors associated with oropharyngeal and non-oropharyngeal HNSCC incidence and outcomes separately.

METHODS: We constructed a retrospective cohort study of 45,052 PLWH aged 18 or above from the national Veteran Affairs (VA) Corporate Data from 1999 to 2015. We extracted demographic data and risk factor information, including history of alcohol abuse, smoking, CD4 count …

The Intriguing Interaction Of Escherichia Coli With The Host Environment And Innovative Strategies To Interfere With Colonization: A Summary Of The 2019 E. Coli And The Mucosal Immune System Meeting, Eric Cox, Meryem Aloulou, James M Fleckenstein, Christina Schäffer, Åsa Sjöling, Stephanie Schüller, Kurt Hanevik, Bert Devriendt, Weiping Zhang, Ann-Mari Svennerholm, Edward G Dudley

Open Access Publications

The third

Transcriptional Remodeling Patterns In Murine Dendritic Cells Infected With Paracoccidioides Brasiliensis: More Is Not Necessarily Better, Calliandra M De-Souza-Silva, Fabián Andrés Hurtado, Aldo Henrique Tavares, Getúlio P De Oliveira, Taina Raiol, Christiane Nishibe, Daniel Paiva Agustinho, Nalvo Franco Almeida, Maria Emília Machado Telles Walter, André Moraes Nicola, Anamélia Lorenzetti Bocca, Patrícia Albuquerque, Ildinete Silva-Pereira

Open Access Publications

Most people infected with the fungus

Design And Development Of The Pediatric Urology Recovery After Surgery Endeavor (Pursue) Multicentre Pilot And Exploratory Study, Kyle O Rove, Andrew C Strine, Duncan T Wilcox, Gino J Vricella, Timothy P Welch, Brian Vanderbrink, David I Chu, Rajeev Chaudhry, Rebecca S Zee, Megan A Brockel, Pursue Study Group

Open Access Publications

INTRODUCTION: Lower urinary tract reconstruction in paediatric urology represents a physiologically stressful event that is associated with high complication rates, including readmissions and emergency room visits. Enhanced recovery after surgery (ERAS) protocol is a set of multidisciplinary, perioperative strategies designed to expedite surgical recovery without adversely impacting readmission or reoperation rates. Early paediatric urology data demonstrated ERAS reduced complications in this population.

METHODS AND ANALYSIS: In 2016, a working group of paediatric urologists and anaesthesiologists convened to develop an ERAS protocol suitable for patients undergoing lower urinary tract reconstruction and define study process measures, patient-reported outcomes and clinically relevant outcomes …

Mild Traumatic Brain Injury Is Associated With Effect Of Inflammation On Structural Changes Of Default Mode Network In Those Developing Chronic Pain, Xuan Niu, Lijun Bai, Yingxiang Sun, Yuan Wang, Guanghui Bai, Bo Yin, Shan Wang, Shuoqiu Gan, Xiaoyan Jia, Hongjuan Liu

Open Access Publications

BACKGROUND: Mild traumatic brain injury (mTBI) has a higher prevalence (more than 50%) of developing chronic posttraumatic headache (CPTH) compared with moderate or severe TBI. However, the underlying neural mechanism for CPTH remains unclear. This study aimed to investigate the inflammation level and cortical volume changes in patients with acute PTH (APTH) and further examine their potential in identifying patients who finally developed CPTH at follow-up.

METHODS: Seventy-seven mTBI patients initially underwent neuropsychological measurements, 9-plex panel of serum cytokines and MRI scans within 7 days post-injury (T-1) and 54 (70.1%) of patients completed the same protocol at a 3-month follow-up …

Structure Of The Receptor Binding Domain Of Envp(B)1, An Endogenous Retroviral Envelope Protein Expressed In Human Tissues, Kevin R Mccarthy, Joseph L Timpona, Simon Jenni, Louis-Marie Bloyet, Vesna Brusic, Welkin E Johnson, Sean P J Whelan, Lindsey R Robinson-Mccarthy

Open Access Publications

EnvP(b)1 is an endogenous retroviral envelope gene found in human and other primate genomes. We report EnvP(b)1 sequences in primate genomes consistent with an integration event between 40 and 71 million years ago. Using a highly specific polyclonal antiserum raised against the putative receptor binding domain (RBD) of human EnvP(b)1, we detected expression in human placenta, ovaries, and thymus. We found that EnvP(b)1 is proteolytically processed, and using cell-cell fusion assays in multiple primate cell lines, we demonstrated that extant EnvP(b)1 proteins from a variety of primate genomes are fusogenic. This work supports the idea that EnvP(b)1 is under purifying …

Metachronous Cutaneous Squamous Cell Carcinoma In A Young Patient As The Only Presenting Symptom To Uncover Lynch Syndrome With Mlh1 Germline Mutation, Karam Khaddour, Ryan C Fields, Michael Ansstas, Ilana S Rosman, George Ansstas

Open Access Publications

BACKGROUND: Cutaneous malignancies are rare complications of Lynch syndrome and can include Muir-Torre and Turcot syndromes that are associated with sebaceous gland tumors and keratoacanthomas. The incidence and clinical course of cutaneous squamous cell carcinoma have not been well documented in Lynch syndrome due to its rarity.

CASE PRESENTATION: A 49-year male presented with an enlarging groin skin lesion that was biopsed and demonstrated cutaneous squamous cell carcinoma for which he underwent a surgical resection. The patient experienced later a recurrence of cutaneous squamous cell carcinoma around the resected margins. Next generation sequencing of tumor tissue revealed mutations in MSH6 …

Multivariate Lesion-Behavior Mapping Of General Cognitive Ability And Its Psychometric Constituents, Mark Bowren, Ralph Adolphs, Joel Bruss, Kenneth Manzel, Maurizio Corbetta, Daniel Tranel, Aaron D. Boes

Open Access Publications

General cognitive ability, or general intelligence (g), is central to cognitive science, yet the processes that constitute it remain unknown, in good part because most prior work has relied on correlational methods. Large-scale behavioral and neuroanatomical data from neurologic patients with focal brain lesions can be leveraged to advance our understanding of the key mechanisms of g, as this approach allows inference on the independence of cognitive processes along with elucidation of their respective neuroanatomical substrates. We analyzed behavioral and neuroanatomical data from 402 humans (212 males; 190 females) with chronic, focal brain lesions. Structural equation models (SEMs) demonstrated a …

Tfeb Transcriptional Responses Reveal Negative Feedback By Bhlhe40 And Bhlhe41, Kimberly L Carey, Geraldine L C Paulus, Lingfei Wang, Dale R Balce, Jessica W Luo, Phil Bergman, Ianina C Ferder, Lingjia Kong, Nicole Renaud, Shantanu Singh, Maria Kost-Alimova, Beat Nyfeler, Kara G Lassen, Herbert W Virgin, Ramnik J Xavier

Open Access Publications

Transcription factor EB (TFEB) activates lysosomal biogenesis genes in response to environmental cues. Given implications of impaired TFEB signaling and lysosomal dysfunction in metabolic, neurological, and infectious diseases, we aim to systematically identify TFEB-directed circuits by examining transcriptional responses to TFEB subcellular localization and stimulation. We reveal that steady-state nuclear TFEB is sufficient to activate transcription of lysosomal, autophagy, and innate immunity genes, whereas other targets require higher thresholds of stimulation. Furthermore, we identify shared and distinct transcriptional signatures between mTOR inhibition and bacterial autophagy. Using a genome-wide CRISPR library, we find TFEB targets that protect cells from or sensitize …

Treatment Of Epithelial Ovarian Cancer, Lindsay Kuroki, Saketh R Guntupalli

Open Access Publications

Ovarian cancer is the third most common gynecologic malignancy worldwide but accounts for the highest mortality rate among these cancers. A stepwise approach to assessment, diagnosis, and treatment is vital to appropriate management of this disease process. An integrated approach with gynecologic oncologists as well as medical oncologists, pathologists, and radiologists is of paramount importance to improving outcomes. Surgical cytoreduction to R0 is the mainstay of treatment, followed by adjuvant chemotherapy. Genetic testing for gene mutations that affect treatment is the standard of care for all women with epithelial ovarian cancer. Nearly all women will have a recurrence, and the …

Ante- And Postmortem Tau In Autosomal Dominant And Late-Onset Alzheimer's Disease, Charles D Chen, Timothy R Holden, Brian A Gordon, Erin E Franklin, Yan Li, Dean W Coble, Hongbo Luo, Randall J Bateman, Dominantly Inherited Alzheimer Network (Dian) And For The Dominantly Inherited Alzheimer Network Trials Unit (Dian-Tu), Beau M Ances, Richard J Perrin, Tammie L S Benzinger, Nigel J Cairns, John C Morris

Open Access Publications

Antemortem tau positron emission tomography imaging suggests elevated tau pathology in autosomal dominant versus late-onset Alzheimer's disease at equivalent clinical stages, but does not implicate the specific tau pathologies responsible. Here we made stereological measurements of tau neurofibrillary tangles, neuritic plaques, and neuropil threads and found compared to late-onset Alzheimer's disease, autosomal dominant Alzheimer's disease showed even greater tangle and thread burdens. Regional tau burden resembled that observed in tau imaging of a separate cohort at earlier clinical stages. Finally, our results suggest tau imaging measures total tau burden in Alzheimer's disease, composed predominantly of tangle and thread pathology.

Urban-Rural Disparities In Access To Low-Dose Computed Tomography Lung Cancer Screening In Missouri And Illinois, Karthik W Rohatgi, Christine M Marx, Marquita W Lewis-Thames, Jingxia Liu, Graham A Colditz, Aimee S James

Open Access Publications

INTRODUCTION: Low-dose computed tomography (LDCT) lung cancer screening is recommended for current and former smokers who meet eligibility criteria. Few studies have quantitatively examined disparities in access to LDCT screening. The objective of this study was to examine relationships between 1) rurality, sociodemographic characteristics, and access to LDCT lung cancer screening and 2) screening access and lung cancer mortality.

METHODS: We used census block group and county-level data from Missouri and Illinois. We defined access to screening as presence of an accredited screening center within 30 miles of residence as of May 2019. We used mixed-effects logistic models for screening …

Moonshots For Aging, Sandeep Kumar, Timothy R Peterson

Open Access Publications

As the global population ages, there is increased interest in living longer and improving one's quality of life in later years. However, studying aging - the decline in body function - is expensive and time-consuming. And despite research success to make model organisms live longer, there still aren't really any feasible solutions for delaying aging in humans. With space travel, scientists and engineers couldn't know what it would take to get to the moon. They had to extrapolate from theory and shorter-range tests. Perhaps with aging, we need a similar moonshot philosophy. And though "shot" might imply medicine, perhaps we …

Assessment Of Neighborhood Poverty, Cognitive Function, And Prefrontal And Hippocampal Volumes In Children, Rita L. Taylor, Shelly R. Cooper, Joshua J. Jackson, Deanna M. Barch

Open Access Publications

Importance: The association between poverty and unfavorable cognitive outcomes is robust, but most research has focused on individual household socioeconomic status (SES). There is increasing evidence that neighborhood context explains unique variance not accounted for by household SES.

Objective: To evaluate whether neighborhood poverty (NP) is associated with cognitive function and prefrontal and hippocampal brain structure in ways that are dissociable from household SES.

Design, Setting, and Participants: This cross-sectional study used a baseline sample of the ongoing longitudinal Adolescent Brain Cognitive Development (ABCD) Study. The ABCD Study will follow participants for assessments each year for 10 years. Data were …

Blood Plasma Phosphorylated-Tau Isoforms Track Cns Change In Alzheimer's Disease, Nicolas R. Barthélemy, Kanta Horie, Chihiro Sato, Randall J. Bateman

Open Access Publications

Highly sensitive and specific plasma biomarkers for Alzheimer's disease (AD) have the potential to improve diagnostic accuracy in the clinic and facilitate research studies including enrollment in prevention and treatment trials. We recently reported CSF tau hyperphosphorylation, especially on T217, is an accurate predictor of β-amyloidosis at asymptomatic and symptomatic stages. In the current study, we determine by mass spectrometry the potential utility of plasma p-tau isoforms to detect AD pathology and investigate CSF and plasma tau isoforms' profile relationships. Plasma tau was truncated as previously described in CSF. CSF and plasma measures of p-tau-217 and p-tau-181 were correlated. No …