9,711 results match your criteria Kennedy Disease


Cementless unicompartmental knee replacement achieves better ten-year clinical outcomes than cemented: a systematic review.

Knee Surg Sports Traumatol Arthrosc 2020 Jul 1. Epub 2020 Jul 1.

Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Oxford, OX3 7LD, UK.

Purpose: The aim of this study was to report and compare the long-term revision rate, revision indications and patient reported outcome measures of cemented and cementless unicompartmental knee replacements (UKR).

Methods: Databases Medline, Embase and Cochrane Central of Controlled Trials were searched to identify all UKR studies reporting the ≥ 10 year clinical outcomes. Revision rates per 100 component years [% per annum (% pa)] were calculated by fixation type and then, subgroup analyses for fixed and mobile bearing UKRs were performed. Read More

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http://dx.doi.org/10.1007/s00167-020-06091-5DOI Listing

The relationship of cognitive change over time to the self-reported Ascertain Dementia 8-item Questionnaire in a general population.

Arch Clin Neuropsychol 2020 Jul 1. Epub 2020 Jul 1.

Department of Medicine, University of Alabama at Birmingham, Birmingham, AL, USA.

Objective: The aim of the study was to examine the relationship between longitudinally assessed cognitive functioning and self-reported dementia status using the Ascertain Dementia 8-item questionnaire (AD8) in a national population-based sample.

Methods: The analysis included 14,453 participants from the REasons for Geographic and Racial Differences in Stroke study. A validated cutoff of ≥2 symptoms endorsed on the AD8 (administered 10 years after enrollment) represented positive AD8 status. Read More

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http://dx.doi.org/10.1093/arclin/acz045DOI Listing

Effect of RaceRunning on cardiometabolic disease risk factors and functional mobility in young people with moderate-to-severe cerebral palsy: protocol for a feasibility study.

BMJ Open 2020 Jul 1;10(7):e036469. Epub 2020 Jul 1.

Centre for Health, Activity and Rehabilitation Research, Queen Margaret University Edinburgh, Musselburgh, East Lothian, UK.

Introduction: There is consistent evidence that people with cerebral palsy (CP) do not engage in the recommended physical activity guidelines for the general population from a young age. Participation in moderate-to-vigorous physical activity is particularly reduced in people with CP who have a moderate-to-severe disability. RaceRunning is a growing disability sport that provides an opportunity for people with moderate-to-severe disability to participate in physical activity in the community. Read More

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http://dx.doi.org/10.1136/bmjopen-2019-036469DOI Listing

Impact of obesity and metabolic health status in the development of non-alcoholic fatty liver disease (NAFLD): A United Kingdom population-based cohort study using the health improvement network (THIN).

BMC Endocr Disord 2020 Jun 30;20(1):96. Epub 2020 Jun 30.

Institute of Applied Health Research, University of Birmingham, Edgbaston, Birmingham, B15 2TT, UK.

Background: With the obesity epidemic reaching crisis levels, there has been attention around those who may be resilient to the effects of obesity, termed metabolically healthy obesity (MHO), who initially present without associated metabolic abnormalities. Few longitudinal studies have explored the relationship between MHO and non-alcoholic fatty liver disease (NAFLD), which we address using over 4 million primary care patient records.

Methods: A retrospective population-based longitudinal cohort was conducted using The Health Improvement Network (THIN) database incorporating adults with no history of NAFLD or alcohol excess at baseline. Read More

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http://dx.doi.org/10.1186/s12902-020-00582-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7325099PMC

Genomes: How Genomic Information has been Used to Deal with Past Outbreaks and the COVID-19 Pandemic.

Int J Mol Sci 2020 Jun 26;21(12). Epub 2020 Jun 26.

Centro de Biología Celular y Molecular de Enfermedades, Instituto de Investigaciones Científicas y Servicios de Alta Tecnología (INDICASAT AIP), Panama City 0801, Panama.

In the 21st century, three highly pathogenic betacoronaviruses have emerged, with an alarming rate of human morbidity and case fatality. Genomic information has been widely used to understand the pathogenesis, animal origin and mode of transmission of coronaviruses in the aftermath of the 2002-2003 severe acute respiratory syndrome (SARS) and 2012 Middle East respiratory syndrome (MERS) outbreaks. Furthermore, genome sequencing and bioinformatic analysis have had an unprecedented relevance in the battle against the 2019-2020 coronavirus disease 2019 (COVID-19) pandemic, the newest and most devastating outbreak caused by a coronavirus in the history of mankind. Read More

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http://dx.doi.org/10.3390/ijms21124546DOI Listing

The North American mitochondrial disease registry.

J Transl Genet Genom 2020 28;4:81-90. Epub 2020 Apr 28.

Department of Neurology, Columbia University Medical Center, New York, NY 10032, USA.

Aim: The North American Mitochondrial Disease Consortium (NAMDC) comprises a network of 17 clinical centers with a mission to conduct translational research on mitochondrial diseases. NAMDC is a part of the Rare Disease Clinical Research Network (RDCRN) and is funded by the National Institutes of Health. To foster its mission, NAMDC has implemented a comprehensive Mitochondrial Disease Clinical Registry (hereafter NAMDC Registry), collected biosamples deposited into the NAMDC Biorepository, defined phenotypes and genotypes of specific disorders, collected natural history data, identified outcome measures, characterized safety and long-term toxicity and efficacy of promising therapies, and trained young investigators interested in patient-oriented research in mitochondrial disease. Read More

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http://dx.doi.org/10.20517/jtgg.2020.12DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7323997PMC

Distinct synovial tissue macrophage subsets regulate inflammation and remission in rheumatoid arthritis.

Nat Med 2020 Jun 29. Epub 2020 Jun 29.

Research into Inflammatory Arthritis Centre Versus Arthritis (RACE), .

Immune-regulatory mechanisms of drug-free remission in rheumatoid arthritis (RA) are unknown. We hypothesized that synovial tissue macrophages (STM), which persist in remission, contribute to joint homeostasis. We used single-cell transcriptomics to profile 32,000 STMs and identified phenotypic changes in patients with early/active RA, treatment-refractory/active RA and RA in sustained remission. Read More

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http://dx.doi.org/10.1038/s41591-020-0939-8DOI Listing

Ankle Disarticulation: An Underutilized Approach to Staged Below Knee Amputation-Case Series and Surgical Technique.

J Foot Ankle Surg 2020 Jul - Aug;59(4):869-872

Professor, Department of Plastic and Reconstructive Surgery, MedStar Georgetown University Hospital, Washington, DC. Electronic address:

The staged approach to below knee amputation has proven to be an effective method of achieving functionality after amputation and reducing risk for postamputation complications. Transtibial or "guillotine" amputations are often used as the first-stage amputation. Disarticulation at the ankle joint is an alternative method that can be used with favorable results and benefits. Read More

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http://dx.doi.org/10.1053/j.jfas.2019.10.009DOI Listing
October 2019

Parents labor supply and childhood obesity: Evidence from Scotland.

Econ Hum Biol 2020 Jun 18;38:100897. Epub 2020 Jun 18.

The University of Tampa, Department of Economics, 401 W Kennedy Blvd, Sykes College of Business, Tampa, FL, 33606, United States. Electronic address:

More than one third of children worldwide are overweight or obese. This epidemic proportion makes obesity the most common chronic disease among children with short and long-term adverse effects on both affected children and society. This research examines the effect of the extensive and intensive margins of parental employment on children's body mass index (BMI) z-score and likelihood of belonging to different weight status categories in Scotland. Read More

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http://dx.doi.org/10.1016/j.ehb.2020.100897DOI Listing

Alternative splicing controls cell lineage-specific responses to endogenous innate immune triggers within the extracellular matrix.

Matrix Biol 2020 Jun 26. Epub 2020 Jun 26.

Kennedy Institute of Rheumatology, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Oxford, United Kingdom. Electronic address:

The identification of barely more than 20,000 human genes was amongst the most surprising outcomes of the human genome project. Alternative splicing provides an essential means of expanding the proteome, enabling a single gene to encode multiple, distinct isoforms by selective inclusion or exclusion of exons from mature mRNA. However, mis-regulation of this process is associated with most human diseases. Read More

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http://dx.doi.org/10.1016/j.matbio.2020.06.003DOI Listing

Whole blood profiling of T-cell derived miRNA allows the development of prognostic models in inflammatory bowel disease.

J Crohns Colitis 2020 Jun 29. Epub 2020 Jun 29.

Translational Gastroenterology Unit, Nuffield Department of Medicine, Experimental Medicine Division, University of Oxford, John Radcliffe Hospital, Oxford, United Kingdom.

Background: MicroRNAs (miRNAs) are cell-specific small non-coding RNAs that can regulate gene expression and have been implicated in Inflammatory Bowel Disease (IBD) pathogenesis. In our study, we define the cell-specific miRNA profiles and investigate its biomarker potential in IBD.

Methods: In a 2-stage prospective multi-centre case control study, Next Generation sequencing was performed on a discovery cohort of immunomagnetically separated leucocytes from 32 patients (9 CD, 14 UC, 8 healthy controls) and differentially expressed signals were validated in whole blood in 294 patients (97 UC, 98 CD, 98 non-IBD) using quantitative PCR. Read More

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http://dx.doi.org/10.1093/ecco-jcc/jjaa134DOI Listing

Reframing the approach to heterosexual men in the HIV epidemic in sub-Saharan Africa.

J Int AIDS Soc 2020 Jun;23 Suppl 2:e25510

Centre for Infectious Disease Epidemiology & Research, School of Public Health & Family Medicine, University of Cape Town, Cape Town, South Africa.

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http://dx.doi.org/10.1002/jia2.25510DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7319124PMC

Genetic evidence that higher central adiposity causes gastro-oesophageal reflux disease: a Mendelian-randomization study.

Int J Epidemiol 2020 Jun 26. Epub 2020 Jun 26.

Genetics of Complex Traits, University of Exeter Medical School, Exeter, UK.

Background: Gastro-oesophageal reflux disease (GORD) is associated with multiple risk factors but determining causality is difficult. We used a genetic approach [Mendelian randomization (MR)] to identify potential causal modifiable risk factors for GORD.

Methods: We used data from 451 097 European participants in the UK Biobank and defined GORD using hospital-defined ICD10 and OPCS4 codes and self-report data (N = 41 024 GORD cases). Read More

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http://dx.doi.org/10.1093/ije/dyaa082DOI Listing

Practice pattern variability in the management of acute severe colitis: a UK provider survey.

Frontline Gastroenterol 2020 17;11(4):272-279. Epub 2019 Aug 17.

Department of Gastroenterology, Royal Devon and Exeter NHS Foundation Trust, Exeter, UK.

Introduction: Lack of comparative trial data on dosing regimens of infliximab in patients with acute severe ulcerative colitis (ASUC) failing intravenous corticosteroids has resulted in variability of rescue regimes in ASUC with potential impact on clinical outcomes. We aimed to evaluate practice variability and physician perspectives in decision-making with rescue therapy.

Methodology: An internet-based survey of members of the inflammatory bowel disease (IBD) section of the British Society of Gastroenterology was conducted. Read More

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http://dx.doi.org/10.1136/flgastro-2019-101277DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7307042PMC

Ipilimumab plus nivolumab for patients with metastatic uveal melanoma: a multicenter, retrospective study.

J Immunother Cancer 2020 Jun;8(1)

Memorial Sloan Kettering Cancer Center, Weill Cornell Medical College, New York, New York, USA.

Background: Uveal melanoma (UM) is the most common intraocular malignancy in adults. In contrast to cutaneous melanoma (CM), there is no standard therapy, and the efficacy and safety of dual checkpoint blockade with nivolumab and ipilimumab is not well defined.

Methods: We conducted a retrospective analysis of patients with metastatic UM (mUM) who received treatment with ipilimumab plus nivolumab across 14 academic medical centers. Read More

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http://dx.doi.org/10.1136/jitc-2019-000331DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7319717PMC

The impact of gravidity, symptomatology and timing of infection on placental malaria.

Malar J 2020 Jun 24;19(1):227. Epub 2020 Jun 24.

Division of Maternal Fetal Medicine, Department of Obstetrics Gynecology & Reproductive Sciences, University of California San Francisco, 513 Parnassus Ave. HSE16, Box 0556, San Francisco, CA, 94143, USA.

Background: Placental malaria is associated with increased risk of adverse perinatal outcomes. While primigravidity has been reported as a risk factor for placental malaria, little is known regarding the relationship between gravidity, symptomatology and timing of Plasmodium falciparum infection and the development of placental malaria.

Methods: The aim of this study was to investigate the relationship between the development of placental malaria and gravidity, timing of infection, and presence of symptoms. Read More

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http://dx.doi.org/10.1186/s12936-020-03297-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7315526PMC

Identification of a Blood-Based Protein Biomarker Panel for Lung Cancer Detection.

Cancers (Basel) 2020 Jun 19;12(6). Epub 2020 Jun 19.

Department of Oncology, Luxembourg Institute of Health, 1 A-B Rue Thomas Edison, L-1445 Strassen, Luxembourg.

Lung cancer is the deadliest cancer worldwide, mainly due to its advanced stage at the time of diagnosis. A non-invasive method for its early detection remains mandatory to improve patients' survival. Plasma levels of 351 proteins were quantified by Liquid Chromatography-Parallel Reaction Monitoring (LC-PRM)-based mass spectrometry in 128 lung cancer patients and 93 healthy donors. Read More

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http://dx.doi.org/10.3390/cancers12061629DOI Listing

Coronary vascular growth matches IGF-1-stimulated cardiac growth in fetal sheep.

FASEB J 2020 Jun 23. Epub 2020 Jun 23.

Knight Cardiovascular Institute, Center for Developmental Health, Oregon Health & Science University, Portland, OR, USA.

As loss of contractile function in heart disease could often be mitigated by increased cardiomyocyte number, expansion of cardiomyocyte endowment paired with increased vascular supply is a desirable therapeutic goal. Insulin-like growth factor 1 (IGF-1) administration increases fetal cardiomyocyte proliferation and heart mass, but how fetal IGF-1 treatment affects coronary growth and function is unknown. Near-term fetal sheep underwent surgical instrumentation and were studied from 127 to 134 d gestation (term = 147 d), receiving either IGF-1 LR3 or vehicle. Read More

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http://dx.doi.org/10.1096/fj.202000215RDOI Listing

Quality improvement project identifies factors associated with delay in IBD diagnosis.

Aliment Pharmacol Ther 2020 Jun 23. Epub 2020 Jun 23.

Exeter IBD and Pharmacogenetics Research Group, Exeter, UK.

Background: Delay in the diagnosis of inflammatory bowel disease (IBD) is common and contemporary UK studies are lacking.

Aim: To determine factors associated with, and the consequences of, a prolonged time to diagnosis in IBD.

Methods: This quality improvement study included 304 adults with a new IBD diagnosis made between January 2014 and December 2017 across 49 general practices (GP) and gastroenterology secondary care services. Read More

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http://dx.doi.org/10.1111/apt.15885DOI Listing

Protocolized Exercise Improves Frailty Parameters and Lower Extremity Impairment: A Promising Prehabilitation Strategy for Kidney Transplant Candidates.

Clin Transplant 2020 Jun 23:e14017. Epub 2020 Jun 23.

William J von Liebig Center for Transplantation and Clinical Regeneration, USA.

Background: Frailty and decreased functional status are risk factors for adverse kidney transplant (KT) outcomes. Our objective was to examine the efficacy of an exercise intervention on frailty and decreased functional status in a cohort of patients with advanced chronic kidney disease (CKD).

Methods: We conducted a prospective study involving 21 adults with ≥ stage 4 CKD who were 1) frail or pre-frail by Fried phenotype and/or 2) had lower extremity impairment [Short Physical Performance Battery score ≤ 10]. Read More

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http://dx.doi.org/10.1111/ctr.14017DOI Listing

Tau molecular diversity contributes to clinical heterogeneity in Alzheimer's disease.

Nat Med 2020 Jun 22. Epub 2020 Jun 22.

Alzheimer Research Unit, Department of Neurology, Massachusetts General Hospital, Charlestown, MA, USA.

Alzheimer's disease (AD) causes unrelenting, progressive cognitive impairments, but its course is heterogeneous, with a broad range of rates of cognitive decline. The spread of tau aggregates (neurofibrillary tangles) across the cerebral cortex parallels symptom severity. We hypothesized that the kinetics of tau spread may vary if the properties of the propagating tau proteins vary across individuals. Read More

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http://dx.doi.org/10.1038/s41591-020-0938-9DOI Listing
June 2020
27.363 Impact Factor

Narratives of Gestational Diabetes Provide a Lens to Tailor Postpartum Prevention and Monitoring Counseling.

J Midwifery Womens Health 2020 Jun 22. Epub 2020 Jun 22.

Department of Community Health Sciences, Boston University School of Public Health, Boston, Massachusetts.

Introduction: Women with gestational diabetes mellitus (GDM) have a marked increased risk of early onset type 2 diabetes, but less than half initiate postpartum glucose testing or connect with a primary care provider for continued follow-up after giving birth. This study analyzed women's narratives about their GDM-affected pregnancies to (1) identify different patterns (narrative archetypes) that capture the GDM experience; (2) explore how these patterns relate to awareness of ongoing risk after pregnancy and affect participation in self-care, monitoring, and preventive health care going forward; and (3) explore the use of identified patterns to tailor conversations with patients during prenatal and postpartum care to their actual perceptions and concerns about future risk.

Methods: Open-ended interviews elicited women's experiences and perspectives about GDM and its management. Read More

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http://dx.doi.org/10.1111/jmwh.13122DOI Listing

Sodium bicarbonate to improve physical function in patients over 60 years with advanced chronic kidney disease: the BiCARB RCT.

Health Technol Assess 2020 Jun;24(27):1-90

Health Services Research Unit, University of Aberdeen, Aberdeen, UK.

Background: Advanced chronic kidney disease is common in older people and is frequently accompanied by metabolic acidosis. Oral sodium bicarbonate is used to treat this acidosis, but evidence is lacking on whether or not this provides a net gain in health or quality of life for older people.

Objectives: The objectives were to determine whether or not oral bicarbonate therapy improves physical function, quality of life, markers of renal function, bone turnover and vascular health compared with placebo in older people with chronic kidney disease and mild acidosis; to assess the safety of oral bicarbonate; and to establish whether or not oral bicarbonate therapy is cost-effective in this setting. Read More

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http://dx.doi.org/10.3310/hta24270DOI Listing

Brain Oxygen Extraction Is Differentially Altered by Alzheimer's and Vascular Diseases.

J Magn Reson Imaging 2020 Jun 21. Epub 2020 Jun 21.

The Russell H. Morgan Department of Radiology & Radiological Science, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.

Background: Alzheimer's disease and vascular cognitive impairment (VCI), as well as their concurrence, represent the most common types of cognitive dysfunction. Treatment strategies for these two conditions are quite different; however, there exists a considerable overlap in their clinical manifestations, and most biomarkers reveal similar abnormalities between these two conditions.

Purpose: To evaluate the potential of cerebral oxygen extraction fraction (OEF) as a biomarker for differential diagnosis of Alzheimer's disease and VCI. Read More

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http://dx.doi.org/10.1002/jmri.27264DOI Listing

Predictors of Disease Control After Endoscopic Sinus Surgery Plus Long-Term Local Corticosteroids in CRSwNP.

Am J Rhinol Allergy 2020 Jun 20:1945892420936196. Epub 2020 Jun 20.

Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy.

Background: in the era of new biological agents it is important to identify patients who may benefit from conventional therapies such as endoscopic sinus surgery (ESS) plus long-term local corticosteroids from those with patterns of inflammation that are more difficult to control post-operatively and who may benefit from other therapies.

Objective: determine if preoperative assessment of type and grade of inflammation and clinical factors can predict disease control with ESS plus long-term local corticosteroids in chronic rhinosinusitis with nasal polyps (CRSwNP).

Methods: Eighty patients treated with ESS plus mometasone-furoate 200 μg BID for CRSwNP and followed for at least 1 year were enrolled (November 2017-December 2018) in this prospective observational study. Read More

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http://dx.doi.org/10.1177/1945892420936196DOI Listing

Pregnancy outcomes of women conceiving on antiretroviral therapy (ART) compared to those commenced on ART during pregnancy.

Clin Infect Dis 2020 Jun 20. Epub 2020 Jun 20.

Johns Hopkins University, Department of Pathology, Baltimore, MD, USA.

Background: Globally, the number of HIV-infected women of child-bearing age conceiving on ART is increasing. Evidence of ART safety at conception and during pregnancy and adverse pregnancy outcomes remains conflicting. The PROMISE 1077 breastfeeding (BF) and formula feeding (FF) international multisite trials provide an opportunity to examine the impact of ART at conception on pregnancy outcomes with subsequent pregnancies. Read More

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http://dx.doi.org/10.1093/cid/ciaa805DOI Listing
June 2020
8.886 Impact Factor

Feline Infectious Peritonitis: Update on Pathogenesis, Diagnostics, and Treatment.

Vet Clin North Am Small Anim Pract 2020 Jun 17. Epub 2020 Jun 17.

Department of Biomedical and Diagnostic Sciences, College of Veterinary Medicine, University of Tennessee, Room A205 VMC, 2407 River Drive, Knoxville, TN 37996-4543, USA. Electronic address:

Feline infectious peritonitis (FIP) is a mysterious and lethal disease of cats. The causative agent, feline coronavirus (FCoV), is ubiquitous in most feline populations, yet the disease is sporadic in nature. Mutations in the infecting virus combined with an inappropriate immune response to the FCoV contribute to the development of FIP. Read More

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http://dx.doi.org/10.1016/j.cvsm.2020.05.002DOI Listing

Targeting pheochromocytoma/paraganglioma with polyamine inhibitors.

Metabolism 2020 Jun 18;110:154297. Epub 2020 Jun 18.

Department of Medicine, Division of Endocrinology, University of Florida and Malcom Randall VA Medical Center, Gainesville, FL, USA. Electronic address:

Background: Pheochromocytomas (PCCs) and paragangliomas (PGLs) are neuroendocrine tumors that are mostly benign. Metastatic disease does occur in about 10% of cases of PCC and up to 25% of PGL, and for these patients no effective therapies are available. Patients with mutations in the succinate dehydrogenase subunit B (SDHB) gene tend to have metastatic disease. Read More

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http://dx.doi.org/10.1016/j.metabol.2020.154297DOI Listing
June 2020
3.894 Impact Factor

Overall, anti-malarial, and non-malarial effect of intermittent preventive treatment during pregnancy with sulfadoxine-pyrimethamine on birthweight: a mediation analysis.

Lancet Glob Health 2020 Jul;8(7):e942-e953

Department of Disease Control, Faculty of Infectious and Tropical Disease, London School of Hygiene & Tropical Medicine, London, UK.

Background: Trials of intermittent preventive treatment (IPTp) of malaria in pregnant women that compared dihydroartemisinin-piperaquine with the standard of care, sulfadoxine-pyrimethamine, showed dihydroartemisinin-piperaquine was superior at preventing malaria infection, but not at improving birthweight. We aimed to assess whether sulfadoxine-pyrimethamine shows greater non-malarial benefits for birth outcomes than does dihydroartemisinin-piperaquine, and whether dihydroartemisinin-piperaquine shows greater antimalarial benefits for birth outcomes than does sulfadoxine-pyrimethamine.

Methods: We defined treatment as random assignment to sulfadoxine-pyrimethamine or dihydroartemisinin-piperaquine before pooling individual participant-level data from 1617 HIV-uninfected pregnant women in Kenya (one trial; n=806) and Uganda (two trials; n=811). Read More

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http://dx.doi.org/10.1016/S2214-109X(20)30119-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7303957PMC

Statins for atherosclerotic cardiovascular disease prevention in people living with HIV in Thailand: a cost-effectiveness analysis.

J Int AIDS Soc 2020 Jun;23 Suppl 1:e25494

Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand.

Introduction: People living with HIV (PLHIV) have an elevated risk of atherosclerotic cardiovascular disease (CVD) compared to their HIV-negative peers. Expanding statin use may help alleviate this burden. However, the choice of statin in the context of antiretroviral therapy is challenging. Read More

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http://dx.doi.org/10.1002/jia2.25494DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7305414PMC

Predicting and elucidating the etiology of fatty liver disease: A machine learning modeling and validation study in the IMI DIRECT cohorts.

PLoS Med 2020 Jun 19;17(6):e1003149. Epub 2020 Jun 19.

Genetic and Molecular Epidemiology Unit, Department of Clinical Sciences, Lund University, Malmö, Sweden.

Background: Non-alcoholic fatty liver disease (NAFLD) is highly prevalent and causes serious health complications in individuals with and without type 2 diabetes (T2D). Early diagnosis of NAFLD is important, as this can help prevent irreversible damage to the liver and, ultimately, hepatocellular carcinomas. We sought to expand etiological understanding and develop a diagnostic tool for NAFLD using machine learning. Read More

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http://dx.doi.org/10.1371/journal.pmed.1003149DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7304567PMC

Aberrant sorting of hippocampal complex pyramidal cells in Type I Lissencephaly alters topological innervation.

Elife 2020 Jun 19;9. Epub 2020 Jun 19.

Program in Developmental Neurobiology, Eunice Kennedy-Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, United States.

Layering has been a long-appreciated feature of higher order mammalian brain structures but the extent to which it plays an instructive role in synaptic specification remains unknown. Here we examine the formation of synaptic circuitry under cellular heterotopia in hippocampal CA1, using a mouse model of the human neurodevelopmental disorder Type I Lissencephaly. We identify calbindin-expressing principal cells which are mispositioned under cellular heterotopia. Read More

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http://dx.doi.org/10.7554/eLife.55173DOI Listing

Surgical outcomes in aspirin-exacerbated respiratory disease without aspirin desensitization.

Int Forum Allergy Rhinol 2020 Jun 18. Epub 2020 Jun 18.

Division of Rhinology, Department of Otolaryngology-Head & Neck Surgery, St. Michael's Hospital, University of Toronto, Toronto, ON, Canada.

Background: Aspirin-exacerbated respiratory disease (AERD) represents a severe endotype of chronic rhinosinusitis with nasal polyposis. Although aspirin desensitization (AD) has emerged as an effective therapeutic option, the natural history of AERD without AD remains unclear.

Methods: A retrospective review was conducted of AERD patients who underwent endoscopic sinus surgery (ESS) without AD between 2010 and 2019. Read More

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http://dx.doi.org/10.1002/alr.22626DOI Listing

Ethmoid-to-maxillary opacification ratio: a predictor of postoperative olfaction and outcomes in nasal polyposis?

Int Forum Allergy Rhinol 2020 Jun 18. Epub 2020 Jun 18.

Department of Otolaryngology-Head & Neck Surgery, Medical University of South Carolina, Charleston, SC.

Background: Inflammatory profiles for patients with chronic rhinosinusitis with nasal polyposis (CRSwNP) vary between North American and Asian populations. An elevated ethmoid-to-maxillary (E/M) opacification ratio on preoperative imaging is associated with certain postoperative outcomes in Asian populations and populations that are non-type 2 dominant. In this study we explore this factor in North American/type 2-based populations. Read More

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http://dx.doi.org/10.1002/alr.22625DOI Listing

Pediatric cancer research: Surviving COVID-19.

Pediatr Blood Cancer 2020 Jun 18:e28435. Epub 2020 Jun 18.

Division of Pediatric Hematology/Oncology/BMT, Nationwide Children's Hospital, Columbus, Ohio.

A diverse panel of pediatric cancer advocates and experts, whose collective experience spans the continuum of international academic medicine, industry, government research, and cancer advocacy, recently discussed challenges for pediatric cancer research in the context of coronavirus disease 2019 (COVID-19). Specifically, this special report addresses the following focus areas: (a) the critical role that translational research has played in transforming pediatric cancer outcomes; (b) the current and potential future impact of COVID-19 on pediatric cancer research; (c) target areas of COVID-19 research that may have application in immunity, oncogenesis, and therapeutic discovery; and (d) future considerations and directions in maintaining pediatric cancer research during and after COVID-19. Read More

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http://dx.doi.org/10.1002/pbc.28435DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7323039PMC

Common Variants Coregulate Expression of GBA and Modifier Genes to Delay Parkinson's Disease Onset.

Mov Disord 2020 Jun 18. Epub 2020 Jun 18.

Liggins Institute, The University of Auckland, Auckland, New Zealand.

Background: GBA mutations are numerically the most significant genetic risk factor for Parkinson's disease (PD), yet these mutations have low penetrance, suggesting additional mechanisms.

Objectives: The objective of this study was to determine if the penetrance of GBA in PD can be explained by regulatory effects on GBA and modifier genes.

Methods: Genetic variants associated with the regulation of GBA were identified by screening 128 common single nucleotide polymorphisms (SNPs) in the GBA locus for spatial cis-expression quantitative trail locus (supported by chromatin interactions). Read More

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http://dx.doi.org/10.1002/mds.28144DOI Listing

Disparities in Coronavirus 2019 Reported Incidence, Knowledge, and Behavior Among US Adults.

JAMA Netw Open 2020 06 1;3(6):e2012403. Epub 2020 Jun 1.

The National Bureau of Economic Research, Cambridge, Massachusetts.

Importance: Data from the coronavirus disease 2019 (COVID-19) pandemic in the US show large differences in hospitalizations and mortality across race and geography. However, there are limited data on health information, beliefs, and behaviors that might indicate different exposure to risk.

Objective: To determine the association of sociodemographic characteristics with reported incidence, knowledge, and behavior regarding COVID-19 among US adults. Read More

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http://dx.doi.org/10.1001/jamanetworkopen.2020.12403DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7303811PMC

Development and validation of the gene-expression Predictor of high-grade-serous Ovarian carcinoma molecular subTYPE (PrOTYPE).

Authors:
Aline Talhouk Joshy George Chen Wang Timothy Budden Tuan Zea Tan Derek S Chiu Stefan Kommoss Huei San Leong Stephanie Chen Maria P Intermaggio Blake Gilks Tayyebeh Mehrane Nazeran Mila Volchek Wafaa Elatre Rex C Bentley Janine Senz Amy Lum Veronica Chow Hanwei Sudderuddin Robertson Mackenzie Samuel Leung Geyi Liu Dustin Johnson Billy Chen Australian Ovarian Cancer Study Jennifer Alsop Susana Banerjee Sabine Behrens Clara Bodelon Alison H Brand Louise A Brinton Michael E Carney Yoke-Eng Chiew Kara L Cushing-Haugen Cezary Cybulski Darren Ennis Sian Fereday Renée Turzanski Fortner Jesus García-Donás Aleksandra Gentry-Maharaj Rosalind Glasspool Teodora Goranova Casey S Greene Paul Haluska Holly R Harris Joy Hendley Brenda Y Hernandez Esther Herpel Mercedes Jimenez-Linan Chloe Karpinskyj Scott Harold Kaufmann Gary Keeney Catherine J Kennedy Martin Köbel Jennifer Koziak Melissa C Larson Jenny Lester Liz-Anne Lewsley Jolanta Lissowska Jan Lubiński Hugh Luk Geoff Macintyre Sven Mahner Iain A McNeish Janusz Menkiszak Nikilyn Nevins Ana Osorio Oleg Oszurek Jose Palacios Samantha Hinsley Celeste L Pearce Malcolm C Pike Anna Piskorz Isabelle Ray-Coquard Valerie Rhenius Cristina Rodríguez-Antona Raghwa Sharma Mark E Sherman Dilrini Silva Naveena Singh Hans-Peter Sinn Dennis J Slamon Honglin Song Helen Steed Euan A Stronach Pamela J Thompson Aleksandra Tołoczko-Grabarek Britton Trabert Nadia Traficante Chiu-Chen Tseng Martin Widschwendter Lynne R Wilkens Stacey J Winham Boris J Winterhoff Alicia Beeghly-Fadiel Javier Benitez Andrew Berchuck James D Brenton Robert Brown Jenny Chang-Claude Georgia Chenevix-Trench Anna DeFazio Peter A Fasching Maria J Garcia Simon A Gayther Marc T Goodman Jacek Gronwald Michelle J Henderson Beth Y Karlan Linda E Kelemen Usha Menon Sandra Orsulic Paul D P Pharoah Nicolas Wentzensen Anna H Wu Joellen Shildkraut Mary Anne Rossing Gottfried E Konecny David G Huntsman Ruby Yun-Ju Huang Ellen L Goode Susan J Ramus Jennifer A Doherty David D L Bowtell Michael S Anglesio

Clin Cancer Res 2020 Jun 17. Epub 2020 Jun 17.

Department of Obstetrics and Gynecology, University of British Columbia

Purpose: Gene-expression-based molecular subtypes of high-grade serous tubo-ovarian cancer (HGSOC), demonstrated across multiple studies, may provide improved stratification for molecularly targeted trials. However, evaluation of clinical utility has been hindered by non-standardized methods which are not applicable in a clinical setting. We sought to generate a clinical-grade minimal gene-set assay for classification of individual tumor specimens into HGSOC subtypes and confirm previously reported subtype-associated features. Read More

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http://dx.doi.org/10.1158/1078-0432.CCR-20-0103DOI Listing
June 2020
8.722 Impact Factor

The tumour microenvironment of the upper and lower gastrointestinal tract differentially influences dendritic cell maturation.

BMC Cancer 2020 Jun 17;20(1):566. Epub 2020 Jun 17.

Department of Surgery, Trinity Translational Medicine Institute, Trinity College Dublin, St James's Hospital, Dublin 8, Ireland.

Background: Only 10-30% of oesophageal and rectal adenocarcinoma patients treated with neoadjuvant chemoradiotherapy have a complete pathological response. Inflammatory and angiogenic mediators in the tumour microenvironment (TME) may enable evasion of anti-tumour immune responses.

Methods: The TME influence on infiltrating dendritic cells (DCs) was modelled by treating immature monocyte-derived DCs with Tumour Conditioned Media (TCM) from distinct gastrointestinal sites, prior to LPS-induced maturation. Read More

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http://dx.doi.org/10.1186/s12885-020-07012-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7302160PMC

Population-based targeted sequencing of 54 candidate genes identifies as a susceptibility gene for high-grade serous ovarian cancer.

J Med Genet 2020 Jun 16. Epub 2020 Jun 16.

Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK

Purpose: The known epithelial ovarian cancer (EOC) susceptibility genes account for less than 50% of the heritable risk of ovarian cancer suggesting that other susceptibility genes exist. The aim of this study was to evaluate the contribution to ovarian cancer susceptibility of rare deleterious germline variants in a set of candidate genes.

Methods: We sequenced the coding region of 54 candidate genes in 6385 invasive EOC cases and 6115 controls of broad European ancestry. Read More

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http://dx.doi.org/10.1136/jmedgenet-2019-106739DOI Listing

Comparison of regional flortaucipir PET with quantitative tau immunohistochemistry in three subjects with Alzheimer's disease pathology: a clinicopathological study.

EJNMMI Res 2020 Jun 15;10(1):65. Epub 2020 Jun 15.

Avid Radiopharmaceuticals, 3711 Market St., 7th floor, Philadelphia, PA, 19104, USA.

Background: The objective of this study was to make a quantitative comparison of flortaucipir PET retention with pathological tau and β-amyloid across a range of brain regions at autopsy.

Methods: Patients with dementia (two with clinical diagnosis of AD, one undetermined), nearing the end of life, underwent 20-min PET, beginning 80 min after an injection of ~370 mBq flortaucipir [F]. Neocortical, basal ganglia, and limbic tissue samples were obtained bilaterally from 19 regions at autopsy and subject-specific PET regions of interest corresponding to the 19 sampled target tissue regions in each hemisphere were hand drawn on the PET images. Read More

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http://dx.doi.org/10.1186/s13550-020-00653-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7295920PMC

Human cytomegalovirus pp65 peptide-induced autoantibodies cross-reacts with TAF9 protein and induces lupus-like autoimmunity in BALB/c mice.

Sci Rep 2020 Jun 15;10(1):9662. Epub 2020 Jun 15.

Division of Rheumatology, Allergy and Immunology, Chang Gung Memorial Hospital, Taoyuan, Taiwan.

Human cytomegalovirus (HCMV) has been linked to the triggering of systemic lupus erythematosus (SLE). We proposed that B cell epitope region of HCMV phosphoprotein 65 (HCMVpp65) mimics an endogenous antigen and initiates lupus-like autoimmunity. Amino acid homology between HCMVpp65 and TAF9 (TATA-box binding protein associated factor 9, TAF9) was investigated using a similarity search in NCBI protein BLAST program (BLASTP). Read More

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http://dx.doi.org/10.1038/s41598-020-66804-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7295797PMC

Using Social Media and Technology to Communicate in Pediatric HIV Research: Qualitative Study With Young Adults Living With or Exposed to Perinatal HIV.

JMIR Pediatr Parent 2020 Jun 23;3(1):e20712. Epub 2020 Jun 23.

Department of Epidemiology, Harvard TH Chan School of Public Health, Boston, MA, United States.

Background: As young adults living with perinatal HIV (PHIV) or perinatal HIV exposure but uninfected (PHEU) grow older and manage the challenges and competing demands of young adulthood, new approaches are needed to facilitate their retention in longitudinal research and clinical care beyond in-person clinic visits. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the novel virus that causes coronavirus disease (COVID-19), emerged in the United States in January 2020 and has underscored this need; studies are adapting to remote communication with and data collection from participants. However, there are limited data on communication preferences among young adults who are living with PHIV or PHEU. Read More

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http://dx.doi.org/10.2196/20712DOI Listing

Progression of Alzheimer's Disease by Self-Reported Cancer History in the Alzheimer's Disease Neuroimaging Initiative.

J Alzheimers Dis 2020 Jun 6. Epub 2020 Jun 6.

Division of Gerontology, Geriatrics, and Palliative Care, Department of Medicine, University of Alabama, Birmingham, Birmingham, AL, USA.

Background: Cross-sectional studies suggest self-reported cancer history is associated with decreased risk of Alzheimer's disease (AD). However, little is known about how self-reported cancer affects longitudinal AD progression, the primary outcome in clinical trials and observational studies.

Objective: To determine self-reported cancer history's effect on longitudinal AD progression in an observational study. Read More

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http://dx.doi.org/10.3233/JAD-200108DOI Listing
June 2020
4.151 Impact Factor

Perinatal encephalopathy, the syndrome of intracranial hypertension and associated diagnostic labels in the Commonwealth of Independent States: a systematic review.

Arch Dis Child 2020 Jun 12. Epub 2020 Jun 12.

Regional Office for Europe, World Health Organization, Copenhagen, Denmark.

Background: The WHO reports excessive rates of ill-defined neurological diagnoses and ineffective and potentially harmful drug treatments in children in the Commonwealth of Independent States (CIS). Collectively termed perinatal encephalopathy and the syndrome of intracranial hypertension (PE-SIH), these diagnoses are important contributors to perceived childhood morbidity and disability in the CIS. A systematic compilation of information on PE-SIH is lacking. Read More

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http://dx.doi.org/10.1136/archdischild-2018-315994DOI Listing

Prevalence of Gastrointestinal Symptoms and Fecal Viral Shedding in Patients With Coronavirus Disease 2019: A Systematic Review and Meta-analysis.

JAMA Netw Open 2020 06 1;3(6):e2011335. Epub 2020 Jun 1.

Kansas City Veterans Affairs Medical Center, Kansas City, Missouri.

Importance: Coronavirus disease 2019 (COVID-19) is a global pandemic and can involve the gastrointestinal (GI) tract, including symptoms like diarrhea and shedding of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in feces.

Objective: To provide a pooled estimate of GI symptoms, liver enzyme levels outside reference ranges, and fecal tests positive for SARS-CoV-2 among patients with COVID-19.

Data Sources: An electronic literature search was performed for published (using MEDLINE/PubMed and Embase) and preprint (using bioRxiv and medRxiv) studies of interest conducted from November 1, 2019, to March 30, 2020. Read More

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http://dx.doi.org/10.1001/jamanetworkopen.2020.11335DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7290409PMC

mTADA is a framework for identifying risk genes from de novo mutations in multiple traits.

Nat Commun 2020 Jun 10;11(1):2929. Epub 2020 Jun 10.

Division of Psychiatric Genomics, Department of Genetics and Genomic Sciences, Institute for Genomics and Multiscale Biology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.

Joint analysis of multiple traits can result in the identification of associations not found through the analysis of each trait in isolation. Studies of neuropsychiatric disorders and congenital heart disease (CHD) which use de novo mutations (DNMs) from parent-offspring trios have reported multiple putatively causal genes. However, a joint analysis method designed to integrate DNMs from multiple studies has yet to be implemented. Read More

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http://dx.doi.org/10.1038/s41467-020-16487-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7287090PMC
June 2020
10.742 Impact Factor

Structure and Mechanism of DHHC Protein Acyltransferases.

J Mol Biol 2020 Jun 6. Epub 2020 Jun 6.

Unit on Structural and Chemical Biology of Membrane Proteins, Neurosciences and Cellular and Structural Biology Division, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USA. Electronic address:

S-acylation, whereby a fatty acid chain is covalently linked to a cysteine residue by a thioester linkage, is the most prevalent kind of lipid modification of proteins. Thousands of proteins are targets of this post-translational modification, which is catalyzed by a family of eukaryotic integral membrane enzymes known as DHHC protein acyltransferases (DHHC-PATs). Our knowledge of the repertoire of S-acylated proteins has been rapidly expanding owing to development of the chemoproteomic techniques. Read More

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http://dx.doi.org/10.1016/j.jmb.2020.05.023DOI Listing