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A Review Of Chemotherapy And Radiotherapy Near The End Of Life In Individuals With Metastatic Non-Small Cell Lung Cancer, Benjamin C. Li, Stephanie M. Perkins, Sharon E. Phillips, Sara F. Martin, Samantha Hsieh, Eric T. Shinohara, Mark J. Stavas Sep 2020

A Review Of Chemotherapy And Radiotherapy Near The End Of Life In Individuals With Metastatic Non-Small Cell Lung Cancer, Benjamin C. Li, Stephanie M. Perkins, Sharon E. Phillips, Sara F. Martin, Samantha Hsieh, Eric T. Shinohara, Mark J. Stavas

Open Access Publications

No abstract provided.


Higher Csf Strem2 And Microglia Activation Are Associated With Slower Rates Of Beta-Amyloid Accumulation, Michael Ewers, Laura Piccio, Carlos Cruchaga, Et Al Sep 2020

Higher Csf Strem2 And Microglia Activation Are Associated With Slower Rates Of Beta-Amyloid Accumulation, Michael Ewers, Laura Piccio, Carlos Cruchaga, Et Al

Open Access Publications

Microglia activation is the brain's major immune response to amyloid plaques in Alzheimer's disease (AD). Both cerebrospinal fluid (CSF) levels of soluble TREM2 (sTREM2), a biomarker of microglia activation, and microglia PET are increased in AD; however, whether an increase in these biomarkers is associated with reduced amyloid-beta (Aβ) accumulation remains unclear. To address this question, we pursued a two-pronged translational approach. Firstly, in non-demented and demented individuals, we tested CSF sTREM2 at baseline to predict (i) amyloid PET changes over ∼2 years and (ii) tau PET cross-sectionally assessed in a subset of patients. We found higher CSF sTREM2 associated …


Anti-Human Trem2 Induces Microglia Proliferation And Reduces Pathology In An Alzheimer's Disease Model, Shoutang Wang, Carla M. Yuede, Susan Gilfillan, Marco Colonna, Et Al Sep 2020

Anti-Human Trem2 Induces Microglia Proliferation And Reduces Pathology In An Alzheimer's Disease Model, Shoutang Wang, Carla M. Yuede, Susan Gilfillan, Marco Colonna, Et Al

Open Access Publications

TREM2 is a receptor for lipids expressed in microglia. The R47H variant of human TREM2 impairs ligand binding and increases Alzheimer's disease (AD) risk. In mouse models of amyloid β (Aβ) accumulation, defective TREM2 function affects microglial response to Aβ plaques, exacerbating tissue damage, whereas TREM2 overexpression attenuates pathology. Thus, AD may benefit from TREM2 activation. Here, we examined the impact of an anti-human TREM2 agonistic mAb, AL002c, in a mouse AD model expressing either the common variant (CV) or the R47H variant of TREM2. Single-cell RNA-seq of microglia after acute systemic administration of AL002c showed induction of proliferation in …


Bypass Of Dna Interstrand Crosslinks By A Rev1-Dna Polymerase Ζ Complex, Rachel Bezalel-Buch, Young K. Cheun, Upasana Roy, Orlando D. Schärer, Peter M. Burgers Sep 2020

Bypass Of Dna Interstrand Crosslinks By A Rev1-Dna Polymerase Ζ Complex, Rachel Bezalel-Buch, Young K. Cheun, Upasana Roy, Orlando D. Schärer, Peter M. Burgers

Open Access Publications

DNA polymerase ζ (Pol ζ) and Rev1 are essential for the repair of DNA interstrand crosslink (ICL) damage. We have used yeast DNA polymerases η, ζ and Rev1 to study translesion synthesis (TLS) past a nitrogen mustard-based interstrand crosslink (ICL) with an 8-atom linker between the crosslinked bases. The Rev1-Pol ζ complex was most efficient in complete bypass synthesis, by 2-3 fold, compared to Pol ζ alone or Pol η. Rev1 protein, but not its catalytic activity, was required for efficient TLS. A dCMP residue was faithfully inserted across the ICL-G by Pol η, Pol ζ, and Rev1-Pol ζ. Rev1-Pol …


Hepatic Lipids Promote Liver Metastasis, Yongjia Li, Xinming Su, Nidhi Rohatgi, Yan Zhang, Jonathan R Brestoff, Kooresh I Shoghi, Yalin Xu, Clay F Semenkovich, Charles A Harris, Lindsay L Peterson, Katherine N Weilbaecher, Steven L Teitelbaum, Wei Zou Sep 2020

Hepatic Lipids Promote Liver Metastasis, Yongjia Li, Xinming Su, Nidhi Rohatgi, Yan Zhang, Jonathan R Brestoff, Kooresh I Shoghi, Yalin Xu, Clay F Semenkovich, Charles A Harris, Lindsay L Peterson, Katherine N Weilbaecher, Steven L Teitelbaum, Wei Zou

Open Access Publications

Obesity predisposes to cancer and a virtual universality of nonalcoholic fatty liver disease (NAFLD). However, the impact of hepatic steatosis on liver metastasis is enigmatic. We find that while control mice were relatively resistant to hepatic metastasis, those which were lipodystrophic or obese, with NAFLD, had a dramatic increase in breast cancer and melanoma liver metastases. NAFLD promotes liver metastasis by reciprocal activation initiated by tumor-induced triglyceride lipolysis in juxtaposed hepatocytes. The lipolytic products are transferred to cancer cells via fatty acid transporter protein 1, where they are metabolized by mitochondrial oxidation to promote tumor growth. The histology of human …


Severe Immunosuppression And Not A Cytokine Storm Characterizes Covid-19 Infections, Kenneth E Remy, Monty Mazer, David A Striker, Ali H Ellebedy, Andrew H Walton, Jacqueline Unsinger, Teresa M Blood, Philip A Mudd, Daehan J Yi, Daniel A Mannion, Dale F Osborne, R Scott Martin, Nitin J Anand, James P Bosanquet, Jane Blood, Anne M Drewry, Charles C Caldwell, Isaiah R Turnbull, Scott C Brakenridge, Lyle L Moldwawer, Richard S Hotchkiss Sep 2020

Severe Immunosuppression And Not A Cytokine Storm Characterizes Covid-19 Infections, Kenneth E Remy, Monty Mazer, David A Striker, Ali H Ellebedy, Andrew H Walton, Jacqueline Unsinger, Teresa M Blood, Philip A Mudd, Daehan J Yi, Daniel A Mannion, Dale F Osborne, R Scott Martin, Nitin J Anand, James P Bosanquet, Jane Blood, Anne M Drewry, Charles C Caldwell, Isaiah R Turnbull, Scott C Brakenridge, Lyle L Moldwawer, Richard S Hotchkiss

Open Access Publications

COVID-19-associated morbidity and mortality have been attributed to a pathologic host response. Two divergent hypotheses have been proposed: hyperinflammatory cytokine storm; and failure of host protective immunity that results in unrestrained viral dissemination and organ injury. A key explanation for the inability to address this controversy has been the lack of diagnostic tools to evaluate immune function in COVID-19 infections. ELISpot, a highly sensitive, functional immunoassay, was employed in 27 patients with COVID-19, 51 patients with sepsis, 18 critically ill nonseptic (CINS) patients, and 27 healthy control volunteers to evaluate adaptive and innate immune status by quantitating T cell IFN-ɣ …


Local Complement Activation Is Associated With Primary Graft Dysfunction After Lung Transplantation, Hrishikesh S Kulkarni, Lina Ma, Kaitlyn N Speckhart, Tsuyoshi Takahashi, Derek E Byers, Mary K Porteous, Laurel Kalman, Ramsey R Hachem, Melanie Rushefski, Ja'nia Mcphatter, Marlene Cano, Daniel Kreisel, Brigitte Mittler, John P Atkinson, Andrew E Gelman, Et Al Sep 2020

Local Complement Activation Is Associated With Primary Graft Dysfunction After Lung Transplantation, Hrishikesh S Kulkarni, Lina Ma, Kaitlyn N Speckhart, Tsuyoshi Takahashi, Derek E Byers, Mary K Porteous, Laurel Kalman, Ramsey R Hachem, Melanie Rushefski, Ja'nia Mcphatter, Marlene Cano, Daniel Kreisel, Brigitte Mittler, John P Atkinson, Andrew E Gelman, Et Al

Open Access Publications

BACKGROUNDThe complement system plays a key role in host defense but is activated by ischemia/reperfusion injury (IRI). Primary graft dysfunction (PGD) is a form of acute lung injury occurring predominantly due to IRI, which worsens survival after lung transplantation (LTx). Local complement activation is associated with acute lung injury, but whether it is more reflective of allograft injury compared with systemic activation remains unclear. We proposed that local complement activation would help identify those who develop PGD after LTx. We also aimed to identify which complement activation pathways are associated with PGD.METHODSWe performed a multicenter cohort study at the University …


A Simplified Quantitative Real-Time Pcr Assay For Monitoring Sars-Cov-2 Growth In Cell Culture, Christian Shema Mugisha, Hung R Vuong, Maritza Puray-Chavez, Adam L Bailey, Julie M Fox, Rita E Chen, Alex W Wessel, Jason M Scott, Houda H Harastani, Adrianus C M Boon, Haina Shin, Sebla B Kutluay Sep 2020

A Simplified Quantitative Real-Time Pcr Assay For Monitoring Sars-Cov-2 Growth In Cell Culture, Christian Shema Mugisha, Hung R Vuong, Maritza Puray-Chavez, Adam L Bailey, Julie M Fox, Rita E Chen, Alex W Wessel, Jason M Scott, Houda H Harastani, Adrianus C M Boon, Haina Shin, Sebla B Kutluay

Open Access Publications

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has infected millions within just a few months, causing severe respiratory disease and mortality. Assays to monitor SARS-CoV-2 growth


Co-Clinical Imaging Resource Program (Cirp): Bridging The Translational Divide To Advance Precision Medicine, Kooresh I. Shoghi, Richard Laforest, Daniel S. Marcus, Et Al Sep 2020

Co-Clinical Imaging Resource Program (Cirp): Bridging The Translational Divide To Advance Precision Medicine, Kooresh I. Shoghi, Richard Laforest, Daniel S. Marcus, Et Al

Open Access Publications

The National Institutes of Health's (National Cancer Institute) precision medicine initiative emphasizes the biological and molecular bases for cancer prevention and treatment. Importantly, it addresses the need for consistency in preclinical and clinical research. To overcome the translational gap in cancer treatment and prevention, the cancer research community has been transitioning toward using animal models that more fatefully recapitulate human tumor biology. There is a growing need to develop best practices in translational research, including imaging research, to better inform therapeutic choices and decision-making. Therefore, the National Cancer Institute has recently launched the Co-Clinical Imaging Research Resource Program (CIRP). Its …


Adiponectin Gwas Loci Harboring Extensive Allelic Heterogeneity Exhibit Distinct Molecular Consequences, Cassandra N. Spracklen, Adam E. Locke, Et Al. Sep 2020

Adiponectin Gwas Loci Harboring Extensive Allelic Heterogeneity Exhibit Distinct Molecular Consequences, Cassandra N. Spracklen, Adam E. Locke, Et Al.

Open Access Publications

Loci identified in genome-wide association studies (GWAS) can include multiple distinct association signals. We sought to identify the molecular basis of multiple association signals for adiponectin, a hormone involved in glucose regulation secreted almost exclusively from adipose tissue, identified in the Metabolic Syndrome in Men (METSIM) study. With GWAS data for 9,262 men, four loci were significantly associated with adiponectin: ADIPOQ, CDH13, IRS1, and PBRM1. We performed stepwise conditional analyses to identify distinct association signals, a subset of which are also nearly independent (lead variant pairwise r2<0.01). Two loci exhibited allelic heterogeneity, ADIPOQ and CDH13. Of seven association signals at the ADIPOQ locus, two signals colocalized with adipose tissue expression quantitative trait loci (eQTLs) for three transcripts: trait-increasing alleles at one signal were associated with increased ADIPOQ and LINC02043, while trait-increasing alleles at the other signal were associated with decreased ADIPOQ-AS1. In reporter assays, adiponectin-increasing alleles at two signals showed corresponding directions of effect on transcriptional activity. Putative mechanisms for the seven ADIPOQ signals include a missense variant (ADIPOQ G90S), a splice variant, a promoter variant, and four enhancer variants. Of two association signals at the CDH13 locus, the first signal consisted of promoter variants, including the lead adipose tissue eQTL variant for CDH13, while a second signal included a distal intron 1 enhancer variant that showed ~2-fold allelic differences in transcriptional reporter activity. Fine-mapping and experimental validation demonstrated that multiple, distinct association signals at these loci can influence multiple transcripts through multiple molecular mechanisms.


Perceptions On Diversity In Cardiology: A Survey Of Cardiology Fellowship Training Program Directors, Anna Lisa Crowley, Julie Damp, Melanie S Sulistio, Kathryn Berlacher, Donna M Polk, Robert A Hong, Gaby Weissman, Dorothy Jackson, Chittur A Sivaram, James A Arrighi, Andrew M Kates, Claire S Duvernoy, Sandra J Lewis, Quinn Capers Iv Sep 2020

Perceptions On Diversity In Cardiology: A Survey Of Cardiology Fellowship Training Program Directors, Anna Lisa Crowley, Julie Damp, Melanie S Sulistio, Kathryn Berlacher, Donna M Polk, Robert A Hong, Gaby Weissman, Dorothy Jackson, Chittur A Sivaram, James A Arrighi, Andrew M Kates, Claire S Duvernoy, Sandra J Lewis, Quinn Capers Iv

Open Access Publications

Background The lack of diversity in the cardiovascular physician workforce is thought to be an important driver of racial and sex disparities in cardiac care. Cardiology fellowship program directors play a critical role in shaping the cardiology workforce. Methods and Results To assess program directors' perceptions about diversity and barriers to enhancing diversity, the authors conducted a survey of 513 fellowship program directors or associate directors from 193 unique adult cardiology fellowship training programs. The response rate was 21% of all individuals (110/513) representing 57% of US general adult cardiology training programs (110/193). While 69% of respondents endorsed the belief …


Optimal Co-Clinical Radiomics: Sensitivity Of Radiomic Features To Tumour Volume, Image Noise And Resolution In Co-Clinical T1-Weighted And T2-Weighted Magnetic Resonance Imaging, Sudipta Roy, Timothy D Whitehead, James D Quirk, Amber Salter, Foluso O Ademuyiwa, Shunqiang Li, Hongyu An, Kooresh I Shoghi Sep 2020

Optimal Co-Clinical Radiomics: Sensitivity Of Radiomic Features To Tumour Volume, Image Noise And Resolution In Co-Clinical T1-Weighted And T2-Weighted Magnetic Resonance Imaging, Sudipta Roy, Timothy D Whitehead, James D Quirk, Amber Salter, Foluso O Ademuyiwa, Shunqiang Li, Hongyu An, Kooresh I Shoghi

Open Access Publications

BACKGROUND: Radiomics analyses has been proposed to interrogate the biology of tumour as well as to predict/assess response to therapy in vivo. The objective of this work was to assess the sensitivity of radiomics features to noise, resolution, and tumour volume in the context of a co-clinical trial.

METHODS: Triple negative breast cancer (TNBC) patients were recruited into an ongoing co-clinical imaging trial. Sub-typed matched TNBC patient-derived tumour xenografts (PDX) were generated to investigate optimal co-clinical MR radiomic features. The MR imaging protocol included T1-weighed and T2-weighted imaging. To test the sensitivity of radiomics to resolution, PDX were imaged at …


Un-Linqed: Spontaneous Extrusion Of Newer Generation Implantable Loop Recorders, Joseph Zakhar, Thomas J Blount, Anil K Gehi, Sunita J Ferns Sep 2020

Un-Linqed: Spontaneous Extrusion Of Newer Generation Implantable Loop Recorders, Joseph Zakhar, Thomas J Blount, Anil K Gehi, Sunita J Ferns

Open Access Publications

BACKGROUND: Insertable cardiac monitors (ICMs) are often used for long-term monitoring of cardiac rhythm. The Medtronic's LINQ Reveal ™ is a new generation wireless, automated, and patient responsive subcutaneous ECG monitoring device. Despite several advantages to its small size we have noted an unusually high incidence of extrusion at our center.

METHODS: & Results: We conducted a retrospective case analysis to review Reveal LINQs implanted at our center. All devices were inserted using the provided insertion tools. Patients with extruded devices were identified and details regarding the site and technique of insertion, incision closure, use of peri-operative antibiotics, and follow-up …


Outcomes Of Outpatient Parenteral Antimicrobial Therapy With Ceftriaxone For Methicillin-Susceptible Staphylococcus Aureus Bloodstream Infections—A Single-Center Observational Study, Yasir Hamad, Lee Connor, Thomas C. Bailey, Ige A. George Sep 2020

Outcomes Of Outpatient Parenteral Antimicrobial Therapy With Ceftriaxone For Methicillin-Susceptible Staphylococcus Aureus Bloodstream Infections—A Single-Center Observational Study, Yasir Hamad, Lee Connor, Thomas C. Bailey, Ige A. George

Open Access Publications

Background:

Methods: Adult patients with methicillin-susceptible

Results: Of 243 patients included, 148 (61%) were discharged on ceftriaxone and 95 (39%) were discharged on either oxacillin or cefazolin. The ceftriaxone group had lower rates of intensive care unit care, endocarditis, and shorter duration of bacteremia, but higher rates of cancer diagnoses. There was no significant difference in the composite adverse outcome in the oxacillin or cefazolin group vs the ceftriaxone group (18 [19%] vs 31 [21%];

Conclusions: For patients with MSSA BSI discharged on OPAT, within the limitations of the small numbers and retrospective design we did not find a significant …


The Effect Of Exposure To Long Working Hours On Stroke: A Systematic Review And Meta-Analysis From The Who/Ilo Joint Estimates Of The Work-Related Burden Of Disease And Injury, Alexis Descatha, Bradley A Evanoff, Et Al Sep 2020

The Effect Of Exposure To Long Working Hours On Stroke: A Systematic Review And Meta-Analysis From The Who/Ilo Joint Estimates Of The Work-Related Burden Of Disease And Injury, Alexis Descatha, Bradley A Evanoff, Et Al

Open Access Publications

BACKGROUND: The World Health Organization (WHO) and the International Labour Organization (ILO) are developing joint estimates of the work-related burden of disease and injury (WHO/ILO Joint Estimates), with contributions from a large network of individual experts. Evidence from mechanistic data and prior studies suggests that exposure to long working hours may cause stroke. In this paper, we present a systematic review and meta-analysis of parameters for estimating the number of deaths and disability-adjusted life years from stroke that are attributable to exposure to long working hours, for the development of the WHO/ILO Joint Estimates.

OBJECTIVES: We aimed to systematically review …


Association Of Guideline Publication And Delays To Treatment In Pediatric Status Epilepticus, Iván Sánchez Fernández, Réjean M Guerriero, Et Al Sep 2020

Association Of Guideline Publication And Delays To Treatment In Pediatric Status Epilepticus, Iván Sánchez Fernández, Réjean M Guerriero, Et Al

Open Access Publications

OBJECTIVE: To determine whether publication of evidence on delays in time to treatment shortens time to treatment in pediatric refractory convulsive status epilepticus (rSE), we compared time to treatment before (2011-2014) and after (2015-2019) publication of evidence of delays in treatment of rSE in the Pediatric Status Epilepticus Research Group (pSERG) as assessed by patient interviews and record review.

METHODS: We performed a retrospective analysis of a prospectively collected dataset from June 2011 to September 2019 on pediatric patients (1 month-21 years of age) with rSE.

RESULTS: We studied 328 patients (56% male) with median (25th-75th percentile [p

CONCLUSION: Publication …


Technical Challenges Of Heart Avoidance For Synchronous Breast And Lung Cancers In A Postmenopausal Female: A Planning Case Report From A Safety-Net Hospital, Christophe Marques, Joshua Schiff, Fahad Momin, Nicole Mcallister, Richard L Jennelle, Shelly X Bian, Naomi R Schechter, Stella K Yoo Sep 2020

Technical Challenges Of Heart Avoidance For Synchronous Breast And Lung Cancers In A Postmenopausal Female: A Planning Case Report From A Safety-Net Hospital, Christophe Marques, Joshua Schiff, Fahad Momin, Nicole Mcallister, Richard L Jennelle, Shelly X Bian, Naomi R Schechter, Stella K Yoo

Open Access Publications

No abstract provided.


Reducing Antibiotic Prescribing And Addressing The Global Problem Of Antibiotic Resistance By Targeted Hygiene In The Home And Everyday Life Settings: A Position Paper, Jean-Yves Maillard, Sally F Bloomfield, Patrice Courvalin, Sabiha Y Essack, Sumanth Gandra, Charles P Gerba, Joseph R Rubino, Elizabeth A Scott Sep 2020

Reducing Antibiotic Prescribing And Addressing The Global Problem Of Antibiotic Resistance By Targeted Hygiene In The Home And Everyday Life Settings: A Position Paper, Jean-Yves Maillard, Sally F Bloomfield, Patrice Courvalin, Sabiha Y Essack, Sumanth Gandra, Charles P Gerba, Joseph R Rubino, Elizabeth A Scott

Open Access Publications

Antimicrobial resistance (AMR) continues to threaten global health. Although global and national AMR action plans are in place, infection prevention and control is primarily discussed in the context of health care facilities with home and everyday life settings barely addressed. As seen with the recent global SARS-CoV-2 pandemic, everyday hygiene measures can play an important role in containing the threat from infectious microorganisms. This position paper has been developed following a meeting of global experts in London, 2019. It presents evidence that home and community settings are important for infection transmission and also the acquisition and spread of AMR. It …


Malignant Cell-Specific Cxcl14 Promotes Tumor Lymphocyte Infiltration In Oral Cavity Squamous Cell Carcinoma, Anuraag Parikh, Juneho Shin, William Faquin, Derrick T Lin, Itay Tirosh, John B Sunwoo, Sidharth V Puram Sep 2020

Malignant Cell-Specific Cxcl14 Promotes Tumor Lymphocyte Infiltration In Oral Cavity Squamous Cell Carcinoma, Anuraag Parikh, Juneho Shin, William Faquin, Derrick T Lin, Itay Tirosh, John B Sunwoo, Sidharth V Puram

Open Access Publications

OBJECTIVES: To explore lymphocyte infiltration as a potential mechanism behind CXCL14-mediated tumor growth suppression in oral cavity squamous cell carcinoma (OSCC).

METHODS: We analyzed single cell RNA-sequencing (scRNA-seq) data from OSCC to identify expression changes among malignant cells in lymph nodes (LN) versus primary tumors. CXCL14 expression in murine OSCC cell lines was quantified using qRT-PCR. Short hairpin RNA knockdown of CXCL14 was performed in mouse oral cavity (MOC)1 cells, and CXCL14 overexpression was performed in MOC2 cells. Cells in each condition were injected into C57BL/6 mice with and without T cell depletion, and tumor volume was measured. At 30 …


Imaging Features Of Neonatal Systemic Juvenile Xanthogranuloma: A Case Report And Review Of The Literature, Siping He, Ke Jin, Xicheng Deng, Zhengzhen Zhou, Robert C Mckinstry, Yong Wang Sep 2020

Imaging Features Of Neonatal Systemic Juvenile Xanthogranuloma: A Case Report And Review Of The Literature, Siping He, Ke Jin, Xicheng Deng, Zhengzhen Zhou, Robert C Mckinstry, Yong Wang

Open Access Publications

Juvenile xanthogranuloma (JXG) is the most common non-Langerhans cell histiocytic disorder in children. This report describes the case of a 28-day-old boy that presented with multiple subcutaneous nodular lesions on the trunk and extremities, and multiple red nodular lesions on the scrotum. Magnetic resonance imaging (MRI) of the brain showed a well-demarcated extra-axial dura-based mass that appeared isointense or slightly hyperintense on T1-weighted images, hypointense on T2-weighted images and had intense enhancement on gadolinium-enhanced T1-weighted images. Computed tomography (CT) or MRI scans of the chest and abdomen revealed multiple scattered nodular or patchy lesions of varying sizes in the lungs, …


Antibiotic Overuse In The Primary Health Care Setting: A Secondary Data Analysis Of Standardised Patient Studies From India, China And Kenya, Giorgia Sulis, Benjamin Daniels, Ada Kwan, Sumanth Gandra, Amrita Daftary, Jishnu Das, Madhukar Pai Sep 2020

Antibiotic Overuse In The Primary Health Care Setting: A Secondary Data Analysis Of Standardised Patient Studies From India, China And Kenya, Giorgia Sulis, Benjamin Daniels, Ada Kwan, Sumanth Gandra, Amrita Daftary, Jishnu Das, Madhukar Pai

Open Access Publications

INTRODUCTION: Determining whether antibiotic prescriptions are inappropriate requires knowledge of patients' underlying conditions. In low-income and middle-income countries (LMICs), where misdiagnoses are frequent, this is challenging. Additionally, such details are often unavailable for prescription audits. Recent studies using standardised patients (SPs) offer a unique opportunity to generate unbiased prevalence estimates of antibiotic overuse, as the research design involves patients with predefined conditions.

METHODS: Secondary analyses of data from nine SP studies were performed to estimate the proportion of SP-provider interactions resulting in inappropriate antibiotic prescribing across primary care settings in three LMICs (China, India and Kenya). In all studies, SPs …


Impact Of Annual And Semi-Annual Mass Drug Administration For Lymphatic Filariasis And Onchocerciasis On Hookworm Infection In Côte D'Ivoire, Agodio Loukouri, Aboulaye Méité, Benjamin G. Koudou, Charles W. Goss, Daphne Lew, Gary J. Weil, Eliezer K. N'Goran, Peter U. Fischer Sep 2020

Impact Of Annual And Semi-Annual Mass Drug Administration For Lymphatic Filariasis And Onchocerciasis On Hookworm Infection In Côte D'Ivoire, Agodio Loukouri, Aboulaye Méité, Benjamin G. Koudou, Charles W. Goss, Daphne Lew, Gary J. Weil, Eliezer K. N'Goran, Peter U. Fischer

Open Access Publications

Mass Drug Administration (MDA) programs to eliminate Lymphatic Filariasis (LF) in western Africa use the anthelminthics ivermectin plus albendazole. These drugs have the potential to impact also Soil-Transmitted Helminth (STH) infections, since the drugs have a broad range of anthelminthic activity. Integration of preventive chemotherapy efforts for LF, onchocerciasis and STH is recommended by the World Health Organization (WHO) in order to avoid duplication of MDA and to reduce costs. The objective of the current study was to determine whether five semi-annual rounds of community-wide MDA to eliminate LF and onchocerciasis have a greater impact on STH than three annual …


Parietal Epithelial Cell Differentiation To A Podocyte Fate In The Aged Mouse Kidney, Natalya V. Kaverina, Diana G. Eng, Jeffrey H. Miner, Jeffrey W. Pippin, Stuart J. Shankland Aug 2020

Parietal Epithelial Cell Differentiation To A Podocyte Fate In The Aged Mouse Kidney, Natalya V. Kaverina, Diana G. Eng, Jeffrey H. Miner, Jeffrey W. Pippin, Stuart J. Shankland

Open Access Publications

Healthy aging is typified by a progressive and absolute loss of podocytes over the lifespan of animals and humans. To test the hypothesis that a subset of glomerular parietal epithelial cell (PEC) progenitors transition to a podocyte fate with aging, dual reporter


Orbitofrontal Cortex Grey Matter Volume Is Related To Children's Depressive Symptoms, Matthew R J Vandermeer, Pan Liu, Ola Mohamed Ali, Andrew R Daoust, Marc F Joanisse, Deanna M Barch, Elizabeth P Hayden Aug 2020

Orbitofrontal Cortex Grey Matter Volume Is Related To Children's Depressive Symptoms, Matthew R J Vandermeer, Pan Liu, Ola Mohamed Ali, Andrew R Daoust, Marc F Joanisse, Deanna M Barch, Elizabeth P Hayden

Open Access Publications

Adults with a history of depression show distinct patterns of grey matter volume (GMV) in frontal cortical (e.g., prefrontal cortex, orbitofrontal cortex) and limbic (e.g., anterior cingulate, amygdala, hippocampus, dorsal striatum) structures, regions relevant to the processing and regulation of reward, which is impaired in the context of depression. However, it is unclear whether these GMV associations with depression precede depressive disorder onset or whether GMV is related to early emerging symptoms or familial depression. To address these questions, we used voxel-based morphometry (VBM) to examine GMV in 85 community-dwelling children (M = 11.12 years, SD = 0.63 years) screened …


Genetic Variants And Functional Pathways Associated With Resilience To Alzheimer's Disease, Logan Dumitrescu, Carlos Cruchaga, Et Al Aug 2020

Genetic Variants And Functional Pathways Associated With Resilience To Alzheimer's Disease, Logan Dumitrescu, Carlos Cruchaga, Et Al

Open Access Publications

Approximately 30% of older adults exhibit the neuropathological features of Alzheimer's disease without signs of cognitive impairment. Yet, little is known about the genetic factors that allow these potentially resilient individuals to remain cognitively unimpaired in the face of substantial neuropathology. We performed a large, genome-wide association study (GWAS) of two previously validated metrics of cognitive resilience quantified using a latent variable modelling approach and representing better-than-predicted cognitive performance for a given level of neuropathology. Data were harmonized across 5108 participants from a clinical trial of Alzheimer's disease and three longitudinal cohort studies of cognitive ageing. All analyses were run …


Pediatric Adhd Symptom Burden Relates To Distinct Neural Activity Across Executive Function Domains, Tehila Nugiel, Mary Abbe Roe, Laura E Engelhardt, Mackenzie E Mitchell, Annie Zheng, Jessica A Church Aug 2020

Pediatric Adhd Symptom Burden Relates To Distinct Neural Activity Across Executive Function Domains, Tehila Nugiel, Mary Abbe Roe, Laura E Engelhardt, Mackenzie E Mitchell, Annie Zheng, Jessica A Church

Open Access Publications

Attention-deficit/hyperactivity disorder (ADHD) is a prevalent childhood disorder marked by inattention and/or hyperactivity symptoms. ADHD may also relate to impaired executive function (EF), but is often studied in a single EF task per sample. The current study addresses the question of unique vs. overlapping relations in brain activity across multiple EF tasks and ADHD symptom burden. Three in-scanner tasks drawn from distinct EF domains (cognitive flexibility, working memory, and inhibition) were collected from children with and without an ADHD diagnosis (N = 63). Whole-brain activity and 11 regions of interest were correlated with parent reports of inattention and hyperactivity symptoms. …


Single-Cell Transcriptome Profiling Reveals Β Cell Maturation In Stem Cell-Derived Islets After Transplantation, Punn Augsornworawat, Kristina G Maxwell, Leonardo Velazco-Cruz, Jeffrey R Millman Aug 2020

Single-Cell Transcriptome Profiling Reveals Β Cell Maturation In Stem Cell-Derived Islets After Transplantation, Punn Augsornworawat, Kristina G Maxwell, Leonardo Velazco-Cruz, Jeffrey R Millman

Open Access Publications

Human pluripotent stem cells differentiated to insulin-secreting β cells (SC-β cells) in islet organoids could provide an unlimited cell source for diabetes cell replacement therapy. However, current SC-β cells generated in vitro are transcriptionally and functionally immature compared to native adult β cells. Here, we use single-cell transcriptomic profiling to catalog changes that occur in transplanted SC-β cells. We find that transplanted SC-β cells exhibit drastic transcriptional changes and mature to more closely resemble adult β cells. Insulin and IAPP protein secretions increase upon transplantation, along with expression of maturation genes lacking with differentiation in vitro, including INS, MAFA, CHGB, …


Cefazolin Inoculum Effect And Methicillin-Susceptible Staphylococcus Aureus Osteoarticular Infections In Children, J Chase Mcneil, Lauren M Sommer, Mary Boyle, Patrick Hogan, Jesus G Vallejo, Kristina G Hultén, Anthony R Flores, Sheldon L Kaplan, Stephanie Fritz Aug 2020

Cefazolin Inoculum Effect And Methicillin-Susceptible Staphylococcus Aureus Osteoarticular Infections In Children, J Chase Mcneil, Lauren M Sommer, Mary Boyle, Patrick Hogan, Jesus G Vallejo, Kristina G Hultén, Anthony R Flores, Sheldon L Kaplan, Stephanie Fritz

Open Access Publications

Select methicillin-susceptible


Developmental Changes In Myocardial B Cells Mirror Changes In B Cells Associated With Different Organs, Cibele Rocha-Resende, Wei Yang, Wenjun Li, Daniel Kreisel, Luigi Adamo, Douglas L Mann Aug 2020

Developmental Changes In Myocardial B Cells Mirror Changes In B Cells Associated With Different Organs, Cibele Rocha-Resende, Wei Yang, Wenjun Li, Daniel Kreisel, Luigi Adamo, Douglas L Mann

Open Access Publications

The naive heart harbors a population of intravascular B cells that make close contact with the cardiac microvasculature. However, the timing of their appearance and their organ specificity remain unknown. To address this knowledge gap, we performed a systematic analysis of B cells isolated from the myocardium and other organs, from embryonic life to adulthood. We found that the phenotype of myocardial B cells changed dynamically during development. While neonatal heart B cells were mostly CD11b+ and CD11b- CD21-CD23-, adult B cells were predominantly CD11b-CD21+CD23+. Histological analysis and intravital microscopy of lung and liver showed that organ-associated B cells in …


Counseling On Access To Lethal Means-Emergency Department (Calm-Ed): A Quality Improvement Program For Firearm Injury Prevention, Kristen L Mueller, Sonya Naganathan, Richard T Griffey Aug 2020

Counseling On Access To Lethal Means-Emergency Department (Calm-Ed): A Quality Improvement Program For Firearm Injury Prevention, Kristen L Mueller, Sonya Naganathan, Richard T Griffey

Open Access Publications

INTRODUCTION: Suicide is the 10

METHODS: We conducted this single-center, prospective, quality improvement study (QI) in an urban, academic ED with over 90,000 annual patient visits. The study looked at adult patients who were discharged after presenting to the ED with suicidal crisis. Assessment of access to lethal means was conducted at the bedside, followed by a counseling session regarding safe storage of lethal means and follow-up via telephone call 48-72 hours after ED discharge. We collected data on patient's sociodemographics, psychiatric history, access to lethal means, lethal means storage methods, the patient's specific plans for lethal means storage after …