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Expanding etiology of progressive familial intrahepatic cholestasis

World Journal of Hepatology 2019年第5期11卷 450-463页

作者： sarah af henkel Judy H Squires Mary Ayers Armando Ganoza Patrick Mckiernan James E Squires Division of Gastroenterology Hepatologyand NutritionEmory School of MedicineAtlantaGA 30322United States Department of Radiology UPMC Children’s Hospital of PittsburghPittsburghPA 15224United States Division of Gastroenterology Hepatologyand NutritionUPMC Children’s Hospital of PittsburghPittsburghPA 15224United States Division of Pediatric Transplantation Department of SurgeryUPMC Children’s Hospital of PittsburghPittsburghPA 15224United States

BACKGROUND Progressive familial intrahepatic cholestasis(PFIC)refers to a disparate group of autosomal recessive disorders that are linked by the inability to appropriately form and excrete bile from hepatocytes,resulting in a hepatocellular form of *** the diagnosis of such disorders had historically been based on pattern recognition of unremitting cholestasis without other identified molecular or anatomic cause,recent scientific advancements have uncovered multiple specific responsible *** variety of identified defects has resulted in an ever-broadening phenotypic spectrum,ranging from traditional benign recurrent jaundice to progressive cholestasis and end-stage liver *** To review current data on defects in bile acid homeostasis,explore the expanding knowledge base of genetic based diseases in this field,and report disease characteristics and *** We conducted a systemic review according to PRISMA *** performed a Medline/PubMed search in February-March 2019 for relevant articles relating to the understanding,diagnosis,and management of bile acid homeostasis with a focus on the family of diseases collectively known as *** only articles were accessed in *** manual search included references of retrieved *** extracted data on disease characteristics,associations with other diseases,and *** was summarized and presented in text,figure,and table *** Genetic-based liver disease resulting in the inability to properly form and secrete bile constitute an important cause of morbidity and mortality in children and increasingly in adults.A growing number of PFIC have been described based on an expanded understanding of biliary transport mechanism defects and the development of a common *** We present a summary of current advances made in a number of areas relevant to both the classically described FIC1(ATP8B1),BSEP(ABCB11),and MDR3(ABCB4)transporter deficiencie

关键词： Cholestasis Progressive familial intrahepatic cholestasis Benign recurrent intrahepatic cholestasis Intrahepatic cholestasis of pregnancy Drug induced cholestasis Bile acids Bile transport

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Gene expression changes in dorsal root ganglia following peripheral nerve injury: roles in inflammation,cell death and nociception

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Neural Regeneration Research 2019年第6期14卷 939-947页

作者： sarah L.Martin Adam J.Reid Alexei Verkhratsky Valerio Magnaghi Alessandro Faroni Blond McIndoe Laboratories School of Biological SciencesUniversity of Manchester University Hospital of South Manchester Department of Plastic and BurnsManchester Faculty of Biology Medicine and HealthUniversity of Manchester Department of Pharmacological and Biomolecular Sciences Università degli Studi di Milano

Subsequent to a peripheral nerve injury, there are changes in gene expression within the dorsal root ganglia in response to the damage. This review selects factors which are well-known to be vital for inflammation, cell death and nociception, and highlights how alterations in their gene expression within the dorsal root ganglia can affect functional recovery. The majority of studies used polymerase chain reaction within animal models to analyse the dynamic changes following peripheral nerve injuries. This review aims to highlight the factors at the gene expression level that impede functional recovery and are hence are potential targets for therapeutic approaches. Where possible the experimental model, specific time-points and cellular location of expression levels are reported.

关键词： Gene expression polymerase chain reaction dorsal root ganglia inflammation nociception cell death peripheral nerve injury Schwann cells satellite glial cells nerve regeneration

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Is SARS-CoV-2 (COVID-19) postviral olfactory dysfunction (PVOD) different from other PVOD?

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World Journal of Otorhinolaryngology-Head and Neck Surgery 2020年第S01期6卷 S26-S32页

作者： sarah A.Imam Wilson P.Lao Priyanka Reddy Shaun A.Nguyen Rodney J.Schlosser Department of Health and Human Performance The CitadelCharlestonSCUSA Loma Linda University School of Medicine Loma LindaCAUSA Department of Otolaryngology-Head and Neck Surgery Medical University of South CarolinaCharlestonSCUSA

Background:The SARS-CoV-2 virus continues to spread rapidly across the globe af-flicting many with Coronavirus Disease 2019(COVID-19).As the infection rates rise,a growing number of SARS-CoV-2 positive individuals have been reported to complain of olfactory distur-bances at an alarming *** olfactory dysfunction(PVOD)is a well-known phenome-non that may explain the olfactory dysfunction reported by SARS-CoV-2 infected ***:A scoping literature review was performed to identify studies that investigated the mechanisms of postviral olfactory *** demonstrating pathophysiological,his-tological,immunochemical,and epidemiological outcomes of PVOD were ***:Fourteen studies were included in addition to one international news *** studies reported destruction of the olfactory epithelium following intranasal inoculation of various viral strains in *** studies isolated pathogenic,anosmia inciting viruses(Para-influenza virus,Human Coronavirus,Rhinovirus)through nucleic acid *** studies demonstrated female predilection in patients with PVOD and COVID-19 associated ol-factory dysfunction,of which the majority were over 50 years ***:PVOD and COVID-19 associated olfactory dysfunction demonstrates considerable similarities in epidemiological trends and disease sequela of other viruses to suggest identical pathophysiological *** studies such as intranasal inoculation and histological biopsies are needed to support our hypothesis.

关键词： Olfaction Olfactory disorders UPSIT SARS-CoV-2(COVID-19) Postviral olfactory dysfunction

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Stroke Prevention in Atrial Fibrillation:Current Strategies and Recommendations

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Cardiovascular Innovations and Applications 2016年第B2期1卷 157-164页

作者： Gerald V.Naccarelli,MD Gregory Caputo,MD Thomas Abendroth,MD Samuel Faber,MD Mauricio Sendra-Ferrer,MD Deborah Wolbrette,MD Soraya Samii,MD,PhD sarah Hussain,MD Mario Gonzalez,MD Penn State Hershey Heart and Vascular Institute Cardiac Electrophysiology ProgramHersheyPAUSA Penn State University College of Medicine HersheyPAUSA

Stroke is the most common complication of atrial fibrillation(af).Guidelines recommend anticoagulant treatment in patients with CHA2DS2VASc scores of>*** data suggests that almost half of patients who should be on therapeutic anticoagulation for stroke prevention in af(SPaf)are *** and more recently developed agents,the"novel anticoagulants"(NOACs)reduce the risk of embolic *** addition,the NOACs also reduce intracranial hemorrhage(ICH)by over 50% compared to *** and bridging strategies involving cardioversion,catheter ablation,and invasive/surgical procedures are *** development of reversal agents for NOACs and the introduction of left atrial appendage occluding devices will evolve the use of newer strategies for preventing stroke in high risk af patients.

关键词： atrial fibrillation stroke anticoagulants

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Novel,non-colonizing,single-strain live biotherapeutic product ADS024 protects against Clostridioides difficile infection challenge in vivo

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世界胃肠病理生理学杂志:英文版(电子版) 2023年第4期14卷 71-85页

作者： Christopher K Murphy Michelle M O’Donnell James W Hegarty sarah Schulz Colin Hill R Paul Ross Mary C Rea Ronald Farquhar Laurent Chesnel Research and Development Adiso Therapeutics Inc.ConcordMA 01742United States APC Microbiome Ireland University College CorkCork T12 K8AFIreland Teagasc Food Research Centre Moorepark FermoyCork P61 C996Ireland Executive Leadership Team Adiso Therapeutics Inc.ConcordMA 01742United States

BACKGROUND The Centers for Disease Control and Prevention estimate that Clostridioides difficile(***)causes half a million infections(CDI)annually and is a major cause of total infectious disease death in the United States,causing inflammation of the colon and potentially deadly *** recently reported the isolation of ADS024,a Bacillus velezensis(***)strain,which demonstrated direct in vitro bactericidal activity against ***,with minimal collateral impact on other members of the gut *** this study,we hypothesized that in vitro activities of ADS024 will translate in vivo to protect against CDI challenge in mouse *** To investigate the in vivo efficacy of *** ADS024 in protecting against CDI challenge in mouse *** To mimic disruption of the gut microbiota,the mice were exposed to vancomycin prior to dosing with *** the mouse single-dose study,the recovery of ADS024 was assessed via microbiological analysis of intestinal and fecal samples at 4 h,8 h,and 24 h after a single oral dose of 5×108 colony-forming units(CFU)/mouse of freshly grown *** single-dose study in miniature swine included groups that had been pre-dosed with vancomycin and that had been exposed to a dose range of ADS024,and a group that was not pre-dosed with vancomycin and received a single dose of *** ADS024 colonies[assessed by quantitative polymerase chain reaction(qPCR)using ADS024-specific primers]were counted on agar *** the 28-d miniature swine study,qPCR was used to measure ADS024 levels from fecal samples after oral administration of ADS024 capsules containing 5×109 CFU for 28 consecutive days,followed by MiSeq compositional sequencing and bioinformatic analyses to measure the impact of ADS024 on *** studies were performed to determine the efficacy of ADS024 in a mouse model of CDI:Study 1 to determine the effects of fresh ADS024 culture and ADS024 spore preparations on the clinical mani

关键词： Gut Single-strain live biotherapeutic product ADS024 Clostridioides difficile Clostridioides difficile challenge model Microbiota

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