10,738 results match your criteria Kennedy Disease


Mast Cells Regulate Ductular Reaction and Intestinal Inflammation in Cholestasis via Farnesoid X Receptor Signaling.

Hepatology 2021 Jun 23. Epub 2021 Jun 23.

Richard L. Roudebush VA Medical Center, Indiana University School of Medicine, Indianapolis, IN, USA.

Background & Aim: Cholestasis is characterized by increased total bile acid (TBA) levels, which are regulated by farnesoid X receptor (FXR)/fibroblast growth factor 15 (FGF15). Primary sclerosing cholangitis (PSC) patients typically present with inflammatory bowel disease (IBD). Mast cells (MCs) (i) express FXR and (ii) infiltrate the liver during cholestasis promoting liver fibrosis. Read More

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The impact of fertility preservation on the timing of breast cancer treatment, recurrence, and survival.

Cancer 2021 Jun 23. Epub 2021 Jun 23.

Center for Infertility and Reproductive Surgery, Department of Obstetrics, Gynecology, and Reproductive Biology, Brigham and Women's Hospital, Boston, Massachusetts.

Background: Many young women with breast cancer undergo fertility preservation (FP) before cancer treatment. This study examined the impact of FP on breast cancer outcomes.

Methods: The authors performed a retrospective cohort study of 272 women aged 20 to 45 years with newly diagnosed stage 0 to III breast cancer who underwent an FP consultation between 2005 and 2017. Read More

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Risk Prediction Model of 90-Day Mortality After Esophagectomy for Cancer.

JAMA Surg 2021 Jun 23. Epub 2021 Jun 23.

Department of Gastrointestinal Surgery, Queen Elizabeth Hospital Birmingham, University Hospitals Birmingham Foundation Trust, Birmingham, United Kingdom.

Importance: Ninety-day mortality rates after esophagectomy are an indicator of the quality of surgical oncologic management. Accurate risk prediction based on large data sets may aid patients and surgeons in making informed decisions.

Objective: To develop and validate a risk prediction model of death within 90 days after esophagectomy for cancer using the International Esodata Study Group (IESG) database, the largest existing prospective, multicenter cohort reporting standardized postoperative outcomes. Read More

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Neuroinflammation: An Integrating Overview of Reactive-Neuroimmune Cell Interactions in Health and Disease.

Mediators Inflamm 2021 31;2021:9999146. Epub 2021 May 31.

Centro de Altos Estudios en Ciencias Humanas y de la Salud, Universidad Abierta Interamericana-Consejo Nacional de Investigaciones Científicas y Técnicas, CAECIHS, UAI-CONICET, Buenos Aires, Argentina.

The concept of central nervous system (CNS) inflammation has evolved over the last decades. Neuroinflammation is the response of reactive CNS components to altered homeostasis, regardless of the cause to be endogenous or exogenous. Neurological diseases, whether traumatic, neoplastic, ischemic, metabolic, toxic, infectious, autoimmune, developmental, or degenerative, involve direct and indirect immune-related neuroinflammation. Read More

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All coffee types decrease the risk of adverse clinical outcomes in chronic liver disease: a UK Biobank study.

BMC Public Health 2021 Jun 22;21(1):970. Epub 2021 Jun 22.

Primary Care & Population Sciences, Faculty of Medicine, University of Southampton, Southampton, SO17 1BJ, UK.

Background: Chronic liver disease (CLD) is a growing cause of morbidity and mortality worldwide, particularly in low to middle-income countries with high disease burden and limited treatment availability. Coffee consumption has been linked with lower rates of CLD, but little is known about the effects of different coffee types, which vary in chemical composition. This study aimed to investigate associations of coffee consumption, including decaffeinated, instant and ground coffee, with chronic liver disease outcomes. Read More

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Effect of Text Messaging Plus Peer Navigation on Viral Suppression Among Youth With HIV in the iCARE Nigeria Pilot Study.

J Acquir Immune Defic Syndr 2021 Aug;87(4):1086-1092

Department of Pediatrics, Northwestern University Feinberg School of Medicine, Chicago, IL.

Background: Consistent with the global trend, youth with HIV (YWH) in Nigeria have high rates of viral nonsuppression. Hence, novel interventions are needed.

Setting: Infectious Diseases Institute, College of Medicine, University of Ibadan, Nigeria. Read More

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Hindsight: Review of Preclinical Disease Models for the Development of New Treatments for Uveal Melanoma.

J Cancer 2021 4;12(15):4672-4685. Epub 2021 Jun 4.

National Institute for Cellular Biotechnology, School of Biotechnology, Dublin City University, Dublin, Ireland.

The molecular, histopathological, genomic and transcriptomic characteristics of uveal melanoma (UM) have identified four molecular subgroups with different clinical outcomes. Despite the improvements in UM classification and biological pathology, current treatments do not reduce the occurrence of metastasis. The development of effective adjuvant and metastatic therapies for UM has been slow and extremely limited. Read More

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Behavioral features in Prader-Willi syndrome (PWS): consensus paper from the International PWS Clinical Trial Consortium.

J Neurodev Disord 2021 Jun 21;13(1):25. Epub 2021 Jun 21.

Centre for Applied Psychology, School of Psychology, University of Birmingham, Edgbaston, Birmingham, UK.

Prader-Willi syndrome (PWS) is a rare neurodevelopmental genetic disorder associated with a characteristic behavioral phenotype that includes severe hyperphagia and a variety of other behavioral challenges such as temper outbursts and anxiety. These behaviors have a significant and dramatic impact on the daily functioning and quality of life for the person with PWS and their families. To date, effective therapies addressing these behavioral challenges have proven elusive, but several potential treatments are on the horizon. Read More

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A contemporary analysis of xanthogranulomatous cholecystitis in a Western cohort.

Surgery 2021 Jun 16. Epub 2021 Jun 16.

Department of Surgery, University of Pennsylvania School of Medicine, Philadelphia, PA. Electronic address:

Background: Xanthogranulomatous cholecystitis is a particularly destructive variant of cholecystitis marked by unique inflammatory changes evident in pathologic specimens. Multiple case series have evaluated this process. However, these often focus on differentiating it from malignancy and have largely been conducted in Asia, where the disease may differ from that seen in the Western hemisphere. Read More

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Personalized management of pheochromocytoma and paraganglioma.

Endocr Rev 2021 Jun 19. Epub 2021 Jun 19.

Section on Medical Neuroendocrinology, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Building 10, CRC, Room 1E-3140, 10 Center Drive MSC-1109, Bethesda, Maryland 20892-1109, US.

Pheochromocytomas/paragangliomas are characterized by a unique molecular landscape that allows their assignment to clusters depending on underlying genetic alterations. With around 30-35% of Caucasian patients (a lower percentage in the Chinese population) showing germline mutations in susceptibility genes, pheochromocytomas/paragangliomas have the highest rate of heritability among all tumors. A further 35-40% of Caucasian patients (a higher percentage in the Chinese population) are affected by somatic driver-mutations. Read More

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Primary cilia are required for the persistence of memory and stabilization of perineuronal nets.

iScience 2021 Jun 24;24(6):102617. Epub 2021 May 24.

Department of Pharmacology, Feinberg School of Medicine, Northwestern University, Room 13-100, Montgomery Ward Memorial Building, Chicago, IL 60611, USA.

It is well established that the formation of episodic memories requires multiple hippocampal mechanisms operating on different time scales. Early mechanisms of memory formation (synaptic consolidation) have been extensively characterized. However, delayed mechanisms, which maintain hippocampal activity as memories stabilize in cortical circuits, are not well understood. Read More

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Spatial and cell type transcriptional landscape of human cerebellar development.

Nat Neurosci 2021 Jun 17. Epub 2021 Jun 17.

Center for Integrative Brain Research, Seattle Children's Research Institute, Seattle, WA, USA.

The human neonatal cerebellum is one-fourth of its adult size yet contains the blueprint required to integrate environmental cues with developing motor, cognitive and emotional skills into adulthood. Although mature cerebellar neuroanatomy is well studied, understanding of its developmental origins is limited. In this study, we systematically mapped the molecular, cellular and spatial composition of human fetal cerebellum by combining laser capture microscopy and SPLiT-seq single-nucleus transcriptomics. Read More

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Hepatocellular carcinoma as a complication of Niemann-Pick disease type C1.

Am J Med Genet A 2021 Jun 17. Epub 2021 Jun 17.

Division of Translational Medicine, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland, USA.

Niemann-Pick disease type C (NPC) is a rare and fatal lysosomal storage disorder characterized by neurodegeneration and hepatic involvement. Mutations in either NPC1 or NPC2, two genes encoding lysosomal proteins, lead to an intracellular accumulation of unesterified cholesterol and sphingolipids in late endosomes/lysosomes. Early cholestatic disease is considered a hallmark of patients with early disease onset. Read More

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Comparison of Outcomes of Pediatric Catheter Ablation by Anesthesia Strategy: A Report from the NCDR IMPACT Registry.

Circ Arrhythm Electrophysiol 2021 Jun 17. Epub 2021 Jun 17.

Division of Cardiology & Center for Pediatric Clinical Effectiveness, The Children's Hospital of Philadelphia & Department of Pediatrics, Perelman School of Medicine at the University of Pennsylvania & Leonard Davis Institute and Center for Cardiovascular Outcomes, Quality, and Evaluative Research, University of Pennsylvania, Philadelphia PA.

- Anesthesia strategies for pediatric ablation procedures include general anesthesia (GA) and monitored anesthesia care (MAC). The effects of anesthesia strategy on arrhythmia inducibility and procedural outcomes have not been investigated. - A multicenter retrospective study was performed, utilizing data from the NCDR IMPACT Registry. Read More

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Children are safe in schools: a review of the Irish experience of reopening schools during the COVID-19 pandemic.

Public Health 2021 Jun 12;195:158-160. Epub 2021 Jun 12.

Office of the Clinical Director for Health Protection, HSE, Ireland; Department of Public Health, HSE Midlands, Tullamore, Ireland.

Objectives: Schools in the Republic of Ireland reopened to students and staff in late August 2020. We sought to determine the test positivity rate of close contacts of cases of coronavirus disease 2019 (COVID-19) in schools during the first half-term of the 2020/2021 academic year.

Methods: National-level data from the schools' testing pathway were interrogated to determine the positivity rate of close contacts of cases of COVID-19 in Irish primary, postprimary and special schools during the first half-term of 2020/2021 academic year. Read More

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Implementation of iPads to Increase Compliance With Delivery of New Parent Education in the Mother-Baby Unit: Retrospective Study.

JMIR Pediatr Parent 2021 Jun 15;4(2):e18830. Epub 2021 Jun 15.

University of South Carolina School of Medicine Greenville, Greenville, SC, United States.

Background: Abusive head trauma (AHT) is a serious health problem affecting more than 3000 infants annually in the United States. The American Academy of Pediatrics and the Centers for Disease Control and Prevention (CDC) recommend that health care providers counsel new parents about the dangers of AHT. Previous studies demonstrate that parental education is effective at reducing AHT events. Read More

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The power and promise of genetic mapping from Plasmodium falciparum crosses utilizing human liver-chimeric mice.

Commun Biol 2021 Jun 14;4(1):734. Epub 2021 Jun 14.

Host Pathogen Interactions Program, Texas Biomedical Research Institute, San Antonio, TX, USA.

Genetic crosses are most powerful for linkage analysis when progeny numbers are high, parental alleles segregate evenly and numbers of inbred progeny are minimized. We previously developed a novel genetic crossing platform for the human malaria parasite Plasmodium falciparum, an obligately sexual, hermaphroditic protozoan, using mice carrying human hepatocytes (the human liver-chimeric FRG NOD huHep mouse) as the vertebrate host. We report on two genetic crosses-(1) an allopatric cross between a laboratory-adapted parasite (NF54) of African origin and a recently patient-derived Asian parasite, and (2) a sympatric cross between two recently patient-derived Asian parasites. Read More

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Pregnancy-associated breast cancer: evaluating maternal and foetal outcomes. A national study.

Breast Cancer Res Treat 2021 Jun 14. Epub 2021 Jun 14.

Department of Medical Oncology, University Hospital Waterford, Waterford, Ireland.

Purpose: Pregnancy-associated breast cancer (PABC) is defined as breast cancer diagnosed during the gestational period (gp-PABC) or in the first postpartum year (pp-PABC). Despite its infrequent occurrence, the incidence of PABC appears to be rising due to the increasing propensity for women to delay childbirth. We have established the first retrospective registry study of PABC in Ireland to examine specific clinicopathological characteristics, treatments, and maternal and foetal outcomes. Read More

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A novel somatic mutation in GNB2 provides new insights to the pathogenesis of Sturge-weber syndrome.

Hum Mol Genet 2021 Jun 14. Epub 2021 Jun 14.

Department of Medical Genetics, Oslo University Hospital and University of Oslo, Oslo, Norway.

Sturge-Weber syndrome (SWS) is a neurocutaneous disorder characterised by vascular malformations affecting skin, eyes and leptomeninges of the brain, which can lead to glaucoma, seizures and intellectual disability. The discovery of a disease-causing somatic missense mutation in the GNAQ gene, encoding an alpha chain of heterotrimeric G-proteins, has initiated efforts to understand how G-proteins contribute to SWS pathogenesis. The mutation is predominantly detected in endothelial cells and is currently believed to affect downstream MAPK-signalling. Read More

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Equine "Idiopathic" and Infundibular Caries-Related Cheek Teeth Fractures: A Long-Term Study of 486 Fractured Teeth in 300 Horses.

Front Vet Sci 2021 28;8:646870. Epub 2021 May 28.

The Royal (Dick) School of Veterinary Studies and The Roslin Institute, The University of Edinburgh, Edinburgh, United Kingdom.

Limited objective information is available on the prevalence of non-traumatic equine cheek teeth fractures, the signalment of affected horses, and the clinical features and treatment of these fractures. This study aims to document patterns of idiopathic and infundibular caries-related cheek teeth fractures in a referral population and evaluate associations between fracture patterns and horse age, Triadan position of affected teeth, clinical signs, and deemed necessity for treatment. A retrospective case review. Read More

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Time to Reflect on Global Health Agenda in Kenya: A Tribute to our Academic and Biomedical Research Mentors.

J Health Care Poor Underserved 2021 ;32(2):xvi-xxi

We submit this column to present a brief biography, a tribute to three departed global health mentors who were instrumental in our careers and for the growth of biomedical research in Kenya. We briefly discuss their educational backgrounds and put forth a set of qualities, values, personal supportive experiences, and achievements that nurtured our careers as scientists. The mentors are Prof. Read More

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January 2021

A Randomized, Double-Blind, Placebo-Controlled, Global Phase 3 Study of Edasalonexent in Pediatric Patients with Duchenne Muscular Dystrophy: Results of the PolarisDMD Trial.

J Neuromuscul Dis 2021 Jun 10. Epub 2021 Jun 10.

Catabasis Pharmaceuticals, Inc., Boston, MA.

Background: Edasalonexent (CAT-1004) is an orally-administered novel small molecule drug designed to inhibit NF-κB and potentially reduce inflammation and fibrosis to improve muscle function and thereby slow disease progression and muscle decline in Duchenne muscular dystrophy (DMD).

Objective: This international, randomized 2 : 1, placebo-controlled, phase 3 study in patients ≥4 - <  8 years old with DMD due to any dystrophin mutation examined the effect of edasalonexent (100 mg/kg/day) compared to placebo over 52 weeks.

Methods: Endpoints were changes in the North Star Ambulatory Assessment (NSAA; primary) and timed function tests (TFTs; secondary). Read More

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Open-Label Evaluation of Eteplirsen in Patients with Duchenne Muscular Dystrophy Amenable to Exon 51 Skipping: PROMOVI Trial.

J Neuromuscul Dis 2021 Jun 8. Epub 2021 Jun 8.

Pediatrics, Center for Gene Therapy, Nationwide Children's Hospital, Columbus, OH, USA.

BackgroundEteplirsen received accelerated FDA approval for treatment of Duchenne muscular dystrophy (DMD) with mutations amenable to exon 51 skipping, based on demonstrated dystrophin production.ObjectiveTo report results from PROMOVI, a phase 3, multicenter, open-label study evaluating efficacy and safety of eteplirsen in a larger cohort.MethodsAmbulatory patients aged 7-16 years, with confirmed mutations amenable to exon 51 skipping, received eteplirsen 30 mg/kg/week intravenously for 96 weeks. Read More

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SARS-CoV-2 vaccination for patients with inflammatory bowel disease - Authors' reply.

Lancet Gastroenterol Hepatol 2021 07;6(7):523-524

Department of Metabolism, Digestion and Reproduction, Imperial College London, London, UK; Department of Gastroenterology, Imperial College Healthcare NHS Trust, London, UK. Electronic address:

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Phase 1 pharmacokinetics and safety study of extended duration dapivirine vaginal rings in the United States.

J Int AIDS Soc 2021 Jun;24(6):e25747

Division of Clinical Pharmacology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA.

Introduction: Vaginal rings are a promising approach to provide a woman-centred, long-acting HIV prevention strategy. Prior trials of a 25 mg dapivirine (DPV) ring have shown a favourable safety profile and approximately 30% risk reduction of HIV-1 infection. Extended duration rings replaced every three months may encourage user adherence, improve health service efficiency and reduce cost overall. Read More

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Phase II trial of the IDO pathway inhibitor indoximod plus pembrolizumab for the treatment of patients with advanced melanoma.

J Immunother Cancer 2021 Jun;9(6)

University of Iowa Holden Comprehensive Cancer Center, Iowa City, Iowa, USA.

Background: The indoleamine 2,3-dioxygenase (IDO) pathway is a key counter-regulatory mechanism that, in cancer, is exploited by tumors to evade antitumor immunity. Indoximod is a small-molecule IDO pathway inhibitor that reverses the immunosuppressive effects of low tryptophan (Trp) and high kynurenine (Kyn) that result from IDO activity. In this study, indoximod was used in combination with a checkpoint inhibitor (CPI) pembrolizumab for the treatment for advanced melanoma. Read More

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Clinical application of a scale to assess genomic healthcare empowerment (GEmS): Process and illustrative case examples.

J Genet Couns 2021 Jun 11. Epub 2021 Jun 11.

Division of Medical Genetics, Department of Pediatrics, Duke University Medical Center, Durham, NC, USA.

The Genome Empowerment Scale (GEmS), developed as a research tool, assesses perspectives of parents of children with undiagnosed disorders about to undergo exome or genome sequencing related to the process of empowerment. We defined genomic healthcare empowerment as follows: perceived ability to understand and seek new information related to the genomic sequencing, manage emotions related to the diagnostic process and outcomes, and utilize genomic sequencing information to the betterment of the individual/child and family. The GEmS consists of four scales, two are primarily emotion-focused (Meaning of a Diagnosis, and Emotional Management of the Process) and two are action-oriented (Seeking Information and Support, and Implications and Planning). Read More

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A phase 1/2 open label nonrandomized clinical trial of intravenous 2-hydroxypropyl-β-cyclodextrin for acute liver disease in infants with Niemann-Pick C1.

Mol Genet Metab Rep 2021 Sep 26;28:100772. Epub 2021 May 26.

Washington University in St. Louis School of Medicine, St. Louis, MO, United States of America.

Introduction: Niemann-Pick C (NPC) is an autosomal recessive disease due to defective NPC1 or NPC2 proteins resulting in -lysosomal storage of unesterified cholesterol in the central nervous system and liver. Acute liver disease in the newborn period may be self-limited or fatal. 2-hydroxypropyl-β-cyclodextrin (2HPBCD) is a cholesterol-binding agent that reduces lysosomal cholesterol storage. Read More

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September 2021

An Advanced Clinician Practitioner in Arthritis Care (ACPAC) Maintains a Positive Patient Experience While Increasing Capacity in Rheumatology Community Care.

J Multidiscip Healthc 2021 3;14:1299-1310. Epub 2021 Jun 3.

Continuing Professional Development, Faculty of Medicine, University of Toronto, Toronto, ON, Canada.

Purpose: This study describes patient care experiences of solo-rheumatologist and co-managed care models utilizing an Advanced Clinician Practitioner in Arthritis Care-trained Extended Role Practitioner (ACPAC-ERP) in three community rheumatology practices.

Materials And Methods: Patients with inflammatory arthritis (IA) were assigned to care provided by one of three (2 senior, 1 early-career) community-based rheumatologists (usual care), or an ACPAC-ERP (co-managed care) for the 6-months following diagnosis. Patient experiences were surveyed using validated measures of patient satisfaction (Patient Doctor Interaction Scale-PDIS), global ratings of confidence and satisfaction, referral patterns, disease activity (RADAI) and self-perceived disability (HAQ-Disability) as well as demographic information. Read More

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The predictive ability of the 313 variant-based polygenic risk score for contralateral breast cancer risk prediction in women of European ancestry with a heterozygous BRCA1 or BRCA2 pathogenic variant.

Genet Med 2021 Jun 10. Epub 2021 Jun 10.

Department of Cancer Epidemiology and Genetics, Masaryk Memorial Cancer Institute, Brno, Czech Republic.

Purpose: To evaluate the association between a previously published 313 variant-based breast cancer (BC) polygenic risk score (PRS) and contralateral breast cancer (CBC) risk, in BRCA1 and BRCA2 pathogenic variant heterozygotes.

Methods: We included women of European ancestry with a prevalent first primary invasive BC (BRCA1 = 6,591 with 1,402 prevalent CBC cases; BRCA2 = 4,208 with 647 prevalent CBC cases) from the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), a large international retrospective series. Cox regression analysis was performed to assess the association between overall and ER-specific PRS and CBC risk. Read More

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