Search Our Scientific Publications & Authors

Curr Opin Pharmacol 2019 Apr 18;45:23-32. Epub 2019 Apr 18.

Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, 161 Cathedral Street, Glasgow G4 0RE, UK.

The endothelium is the single layer of cells lining all blood vessels, and it is a remarkable cardiovascular control centre. Each endothelial cell has only a small number (on average six) of interconnected neighbours. Yet this arrangement produces a large repertoire of behaviours, capable of controlling numerous cardiovascular functions in a flexible and dynamic way. Read More

Clin Pharmacol Ther 2019 Apr 19. Epub 2019 Apr 19.

Office of Clinical Pharmacology, Office of Translational Sciences, Center for Drug Evaluation and Research, US Food and Drug Administration, Silver Spring, Maryland, USA.

Clinical trial designs targeting patient subgroups with certain genetic characteristics may enhance the efficiency of developing drugs for cardiovascular disease (CVD). To evaluate the extent to which genetic knowledge translates to the CVD pipeline, we analyzed how genomic biomarkers are utilized in trials. Phase 2 and 3 trial protocols for investigational new drugs for CVD and risk factors were evaluated for prospective and exploratory genomic biomarker use; drug targets were evaluated for the presence of evidence that genetic variations can impact CVD risk or drug response. Read More

ACS Omega 2019 Mar 15;4(3):5356-5366. Epub 2019 Mar 15.

Department of Physical and Environmental Science, University of Toronto Scarborough, 1265 Military Trail, Toronto, Ontario M1C 1A4, Canada.

Understanding the factors that give rise to tau aggregation and reactive oxygen species (ROS) is the key aspect in Alzheimer's disease pathogenesis. Microtubule (MT) binding repeats of tau protein were suggested to play a critical role in tau aggregation. Here, we show that the interaction of Cu with full-length MT binding repeats R1-R4 leads to the aggregation, and a Cys-based redox chemistry is critically involved in tau aggregation leading to disulfide-bridge dimerization of R2 and R3 and further aggregation into a fibrillar structure. Read More

Sci Adv 2019 Apr 17;5(4):eaau3112. Epub 2019 Apr 17.

Centre for Misfolding Diseases, Department of Chemistry, University of Cambridge, Lensfield Road, Cambridge CB2 1EW, UK.

The aggregates of the Aβ peptide associated with Alzheimer's disease are able to both grow in size as well as generate, through secondary nucleation, new small oligomeric species, that are major cytotoxins associated with neuronal death. Despite the importance of these amyloid fibril-dependent processes, their structural and molecular underpinnings have remained challenging to elucidate. Here, we consider two molecular chaperones: the Brichos domain, which suppresses specifically secondary nucleation processes, and clusterin which our results show is capable of inhibiting, specifically, the elongation of Aβ fibrils at remarkably low substoichiometric ratios. Read More

Front Pharmacol 2019 29;10:277. Epub 2019 Mar 29.

Department of Neurology, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, China.

Wilson's disease (WD) is a rare autosomal recessive inherited disorder of chronic copper toxicosis. Currently, Chinese herbal medicines (CHM) is widely used for WD. Here, we conducted an updated systematic review to investigate the efficacy and safety of CHM for WD and its possible mechanisms. Read More

J Allergy Clin Immunol 2019 Apr 15. Epub 2019 Apr 15.

Respiratory, Inflammation, Autoimmunity IMED Biotech Unit, AstraZeneca, Gothenburg, Sweden.

Background: The role of interleukin-17 immunity is well established in inflammatory diseases like psoriasis and inflammatory bowel disease but not in asthma where further study is required.

Objective: To undertake a deep-phenotyping study of asthmatics with up-regulated interleukin-17 immunity.

Methods: Whole genome transcriptomic analysis was performed using epithelial brushings, bronchial biopsies (91 asthmatics patients and 46 healthy controls) and whole blood samples (n=498) from the U-BIOPRED cohort. Read More

J Neurol Neurosurg Psychiatry 2019 Apr 17. Epub 2019 Apr 17.

MRC Centre for Neuromuscular Diseases, UCL Institute of Neurology and National Hospital for Neurology and Neurosurgery, London, UK

Objectives: Hereditary sensory neuropathy type 1 (HSN1) is a rare, slowly progressive neuropathy causing profound sensory deficits and often severe motor loss. L-serine supplementation is a possible candidate therapy but the lack of responsive outcome measures is a barrier for undertaking clinical trials in HSN1. We performed a 12-month natural history study to characterise the phenotype of HSN1 and to identify responsive outcome measures. Read More

J Clin Med 2019 Apr 16;8(4). Epub 2019 Apr 16.

Bristol Heart Institute, Research Floor Level 7, Bristol Royal Infirmary, Upper Maudlin Street, Bristol BS2 8HW, UK.

Coarctation of the aorta is a form of left ventricular outflow tract obstruction in paediatric patients that can be presented with either bicuspid (BAV) or normal tricuspid (TAV) aortic valve. The congenital BAV is associated with hemodynamic changes and can therefore trigger different molecular remodelling in the coarctation area. This study investigated the proteomic and phosphoproteomic changes associated with BAV for the first time in neonatal coarctation patients. Read More

Cell Rep 2019 Apr;27(3):916-927.e5

Telethon Institute of Genetics and Medicine (TIGEM), Via Campi Flegrei 34, 80078 Pozzuoli (NA), Italy; Department of Chemical, Materials and Industrial Production Engineering, University of Naples Federico II, Piazzale Tecchio 80, 80125 Naples, Italy. Electronic address:

Aggregation of α-synuclein and formation of inclusions are hallmarks of Parkinson's disease (PD). Aggregate formation is affected by cellular environment, but it has been studied almost exclusively in cell-free systems. We quantitatively analyzed α-synuclein inclusion formation and clearance in a yeast cell model of PD expressing either wild-type (WT) α-synuclein or the disease-associated A53T mutant from the galactose (Gal)-inducible promoter. Read More

JCO Clin Cancer Inform 2019 Apr;3:1-17

1 Royal College of Surgeons in Ireland, Dublin, Ireland.

Purpose: Dynamic network models predict clinical prognosis and inform therapeutic intervention by elucidating disease-driven aberrations at the systems level. However, the personalization of model predictions requires the profiling of multiple model inputs, which hampers clinical translation.

Patients And Methods: We applied APOPTO-CELL, a prognostic model of apoptosis signaling, to showcase the establishment of computational platforms that require a reduced set of inputs. Read More

Can Vet J 2019 Apr;60(4):391-398

Department of Large Animal Clinical Sciences, Western College of Veterinary Medicine, University of Saskatchewan, Saskatoon, Saskatchewan S7N 5B4 (Waldner, Parker, Campbell); Public Health Agency of Canada, Saskatoon, Saskatchewan S7N 5B4 (Gow); Animal Welfare Program, Land and Food Systems, University of British Columbia, Vancouver, British Columbia V6T 1Z4 (Wilson).

One hundred cow-calf producers in western Canada were surveyed to determine their perceptions regarding antimicrobial use (AMU) and how these perceptions and other herd management factors were associated with AMU. Veterinarians were the most important source of AMU information. Half of the producers considered antimicrobial resistance (AMR) when choosing antimicrobials, while 24% considered the influence of AMU on AMR in human health. Read More

J Appl Physiol (1985) 2019 Apr 11. Epub 2019 Apr 11.

Biochemistry and Biophysics, University of Pennsylvania School of Medicine, United States.

In glucose homeostasis, glucose concentration is sensed by its metabolism through glucokinase (GCK) and oxidative phosphorylation. Since oxidative phosphorylation is an integral part of the sensory system, glucose sensing is necessarily dependent on oxygen pressure. Much of the dependence on oxygen is suppressed by location of glucose sensing cells in tissues with well regulated blood flow. Read More

PLoS Genet 2019 Apr 16;15(4):e1007739. Epub 2019 Apr 16.

Division of Sleep and Circadian Disorders, Brigham and Women's Hospital, Boston, MA, United States of America.

Sleep disordered breathing (SDB)-related overnight hypoxemia is associated with cardiometabolic disease and other comorbidities. Understanding the genetic bases for variations in nocturnal hypoxemia may help understand mechanisms influencing oxygenation and SDB-related mortality. We conducted genome-wide association tests across 10 cohorts and 4 populations to identify genetic variants associated with three correlated measures of overnight oxyhemoglobin saturation: average and minimum oxyhemoglobin saturation during sleep and the percent of sleep with oxyhemoglobin saturation under 90%. Read More

Ann Surg Oncol 2019 Apr 15. Epub 2019 Apr 15.

The Christie NHS Foundation Trust, Colorectal and Peritoneal Oncology Centre, Manchester, UK.

Introduction: Cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) is an established treatment for pseudomyxoma peritonei resulting from a perforated low-grade appendiceal mucinous neoplasm (LAMN II). In patients with localized disease, a laparoscopic procedure (L-CRS/HIPEC) can be undertaken.

Methods: This video demonstrates L-CRS/HIPEC in a 66-year-old male who had previously undergone an appendicectomy for an LAMN II lesion. Read More

Sci Adv 2019 Apr 10;5(4):eaav4580. Epub 2019 Apr 10.

Shanghai Public Health Clinical Center and School of Basic Medical Sciences, and Key Laboratory of Medical Molecular Virology of MOE/MOH, Fudan University, Shanghai 200032, China.

Continuously emerging highly pathogenic human coronaviruses (HCoVs) remain a major threat to human health, as illustrated in past SARS-CoV and MERS-CoV outbreaks. The development of a drug with broad-spectrum HCoV inhibitory activity would address this urgent unmet medical need. Although previous studies have suggested that the HR1 of HCoV spike (S) protein is an important target site for inhibition against specific HCoVs, whether this conserved region could serve as a target for the development of broad-spectrum pan-CoV inhibitor remains controversial. Read More

Neurology 2019 Apr;92(16):770-771

From the Neurology Department (A.P., F.W.), National Reference Centre for Wilson's Disease (A.P., F.W.), and Neuroradiology Department (A.G.), AP-HP, Lariboisière University Hospital, Paris, France.

Mol Ther 2019 Mar 30. Epub 2019 Mar 30.

Department of Surgery, Duke University Medical Center, Durham, NC 27710, USA. Electronic address:

Endothelial surface and circulating glycoprotein von Willebrand factor (vWF) regulates platelet adhesion and is associated with thrombotic diseases, including ischemic stroke, myocardial infarction, and peripheral vascular disease. Thrombosis, as manifested in these diseases, is the leading cause of disability and death in the western world. Current parenteral antithrombotic and thrombolytic agents used to treat these conditions are limited by a short therapeutic window, irreversibility, and major risk of hemorrhage. Read More

Ann Intern Med 2019 Apr 16. Epub 2019 Apr 16.

Rush Alzheimer's Disease Center, Rush University Medical Center, Chicago, Illinois (P.A.B., L.Y., J.A.S., R.S.W., D.A.B.).

Background: Decreased scam awareness may be an early indicator of impending Alzheimer dementia and its precursor, mild cognitive impairment, but prior studies have not systematically examined the associations between scam awareness and adverse cognitive outcomes.

Objective: To test the hypothesis that low scam awareness is associated with increased risk for incident Alzheimer dementia, mild cognitive impairment, and Alzheimer disease pathology in the brain.

Design: Prospective cohort study of aging. Read More

Neuroepidemiology 2019 Apr 15:1-8. Epub 2019 Apr 15.

Rush Alzheimer's Disease Center, Rush University Medical Center, Chicago, Illinois, USA.

Background/aims: Mobility disability and mild cognitive impairment (MCI) are common in aging and both are associated with risk of death. This study tested the hypothesis that risk of death differs by the order in which mobility disability and MCI occurred.

Methods: One thousand two hundred and sixty-two community-dwelling older adults were unimpaired at baseline and followed annually. Read More

Front Immunol 2019 29;10:649. Epub 2019 Mar 29.

Division of Infectious Disease, Department of Medicine, University of Colorado Anschutz Medical, Aurora, CO, United States.

Innate lymphoid cells (ILCs) are a diverse family of cells that play critical roles in mucosal immunity. One subset of the ILC family, Group 3 ILCs (ILC3s), has been shown to aid in gut homeostasis through the production of IL-22. IL-22 promotes gut homeostasis through its functional effect on the epithelial barrier. Read More

Ther Innov Regul Sci 2019 Apr 14:2168479019841894. Epub 2019 Apr 14.

7 Biostatistics and Research Decision Sciences, Merck Research Laboratories (MRL), Merck & Co, Inc, Kenilworth, NJ, USA.

Alzheimer's disease (AD) has increasingly been recognized as a huge unmet medical need. Currently, there is no approved drug to cure, prevent, or even slow down the disease. It is imperative to develop disease-modifying treatments for AD to alter the underlying disease progression. Read More

Am J Geriatr Psychiatry 2019 Feb 21. Epub 2019 Feb 21.

Behavioral Sciences (RSW, PAB).

Objective: To test the hypothesis that late-life risk aversion is partly a prodromal sign of dementia.

Methods: The authors' design was a longitudinal clinical-pathologic cohort study. The setting included participants' residences in the Chicago area, and a total of 874 older persons without dementia were enrolled. Read More

Vasc Endovascular Surg 2019 Apr 14:1538574419833224. Epub 2019 Apr 14.

1 Department of Veterans Affairs Healthcare Network Upstate New York at Syracuse, Syracuse, NY, USA    .

Introduction: Oral statins reduce intimal hyperplasia (IH) after arterial injury by only ∼25%. Alternative drug delivery systems have gained attention as carriers for hydrophobic drugs. We studied the effects of simvastatin (free vs hyaluronic acid-tagged polysialic acid-polycaprolactone micelles) on vascular smooth muscle cell (VSMC) migration, VSMC proliferation and intimal hyperplasia. Read More

Arch Iran Med 2019 Feb 1;22(2):91-98. Epub 2019 Feb 1.

Endocrinology and Metabolism Research Center (EMRC), Vali-Asr Hospital, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.

Background: We investigated the association of estimated glomerular filtration rate (eGFR) with Framingham risk score (FRS), and actual cardiovascular disease (CVD) in patients with type 2 diabetes (T2DM). We also assessed improvement in FRS for prediction of CVD after inclusion of eGFR and albuminuria.

Methods: A total of 571 patients with T2DM and mean age 55 were divided into 2 groups based on the presence of CVD. Read More

Mol Biol Rep 2019 Apr 12. Epub 2019 Apr 12.

Department of Biochemistry, PGIMER, Chandigarh, India.

Clinical heterogeneity is commonly observed in Wilson disease (WD), including cases with identical ATP7B mutations. It is thought to be an outcome of impairment in other genes involved in cellular copper homeostasis in addition to the mutations in the ATP7B gene. ATOX1, a copper chaperone that delivers copper to ATP7B, is a potential genetic modifier of WD. Read More

J Nucl Med 2019 Apr 12. Epub 2019 Apr 12.

BC Cancer, Canada.

F-DCFPyL, a prostate specific membrane antigen targeting radiotracer, has shown promise as a prostate cancer imaging radiotracer. We evaluated the safety, sensitivity and impact on patient management of F-DCFPyL in the settings of biochemical recurrence of prostate cancer. Subjects with prostate cancer and biochemical recurrence post radical prostatectomy/curative intent radiotherapy were included in this prospective study. Read More

Gut 2019 Apr 12. Epub 2019 Apr 12.

Université Paris-Descartes, Paris-Sorbonne Cité, Paris, France.

Introduction: The optimal trial design for assessing novel therapies in paediatric IBD (PIBD) is a subject of intense ongoing global discussions and debate among the different stakeholders. However, there is a consensus that the current situation in which most medications used in children with IBD are prescribed as off-label without sufficient paediatric data is unacceptable. Shortening the time lag between adult and paediatric approval of drugs is of the upmost importance. Read More

Adv Med Sci 2019 Apr 9;64(2):315-323. Epub 2019 Apr 9.

Department of Medicine A, University Medicine Greifswald, Greifswald, Germany. Electronic address:

The endoplasmic reticulum (ER) is the site of synthesis and folding of membrane and secretory proteins. The fraction of protein passing through the ER represents a large proportion of the total protein in the cell. Protein folding, glycosylation, sorting and transport are essential tasks of the ER and a compromised ER folding network has been recognized to be a key component in the disease pathogenicity of common neurodegenerative, metabolic and malignant diseases. Read More

Open Forum Infect Dis 2019 Apr 10;6(4):ofz124. Epub 2019 Mar 10.

Department of Health Services, Policy, and Practice, Brown University School of Public Health, Providence, Rhode Island.

Background: As antiretroviral therapy has become more effective, persons with HIV live longer and develop conditions that are characteristic of older populations. Understanding changes in comorbid conditions has important implications for the complexity and cost of care, particularly for Medicaid programs and their enrollees, which comprise about 40% of all persons with HIV. Thus, our objective was to examine trends in comorbid conditions for Medicaid enrollees with HIV. Read More

J Virol Methods 2019 Apr 8;269:70-76. Epub 2019 Apr 8.

Arthropod-Borne Animal Diseases Research Unit, USDA, ARS, Manhattan, KS, USA.

Rift Valley fever virus (RVFV) is an important mosquito-borne pathogen with devastating impacts on agriculture and public health. With outbreaks being reported beyond the continent of Africa to the Middle East, there is great concern that RVFV will continue to spread to non-endemic areas such as the Americas and Europe. There is a need for safe and high throughput serological assays for rapid detection of RVFV during outbreaks and for surveillance. Read More

Acad Med 2019 Apr 9. Epub 2019 Apr 9.

R. Gupta is interim chief value director, Olive View-UCLA Medical Center, former medical director of quality improvement, UCLA Health, and assistant professor, Division of General Internal Medicine and Health Services Research, University of California, Los Angeles, Los Angeles, California. L. Roh is director for population health, UCLA Health, University of California Los Angeles, Los Angeles, CA. C. Lee is a program manager for population health, UCLA He Innovation Reportalth, University of California, Los Angeles, Los Angeles, California. D. Reuben is director, Multicampus Program in Geriatrics Medicine and Gerontology, chief, Division of Geriatrics, professor of medicine, and director, UCLA Claude D. Pepper Older Americans Independence Center and Alzheimer's and Dementia Care Program, University of California, Los Angeles, Los Angeles, California. A. Naeim is associate director, Clinical Translational Science Institute, and chief medical officer, Clinical Research, UCLA Campus and Health System, and professor of medicine, Divisions of Hematology-Oncology and Geriatric Medicine, University of California, Los Angeles, Los Angeles, California. J. Wilson is director, Kidney Health Program, Kidney Stone Center and Surgical Consultative Nephrology, UCLA Health, and associate professor, Division of Nephrology, University of California, Los Angeles, Los Angeles, California. S.A. Skootsky is chief medical officer, Faculty Practice Group and Office of Population Health and Accountable Care, UCLA Health, and professor of medicine, Division of General Internal Medicine and Health Services Research, University of California, Los Angeles, Los Angeles, California.

Problem: With the growth in risk-based and accountable care organization contracts, creating value by redesigning care to reduce costs and improve outcomes and the patient experience has become an urgent priority for health care systems.

Approach: In 2016, UCLA (University of California, Los Angeles) Health implemented a system-wide population health approach to identify patient populations with high expenses and promote proactive value-based care. The authors created the Patient Health Value framework to guide value creation: (1) identify patient populations with high expenses and reasons for spending; (2) create design teams to understand the patient story; (3) create custom analytics and spending-based risk stratification; and (4) develop targeted care pathways based on spending risk tiers. Read More

Nat Microbiol 2019 Apr 10. Epub 2019 Apr 10.

Broad Institute of MIT and Harvard, Cambridge, MA, USA.

In the Supplementary Tables 2, 4 and 6 originally published with this Article, the authors mistakenly included sample identifiers in the form of UMCGs rather than UMCG IBDs in the validation cohort; this has now been amended. Read More

Ther Adv Hematol 2019 1;10:2040620719839025. Epub 2019 Apr 1.

Amgen Inc., Thousand Oaks, CA, USA.

Background: Peripheral neuropathy (PN) is a common consequence of multiple myeloma (MM) among those commonly treated with older-generation proteasome inhibitors (PIs). In this study, we evaluated the economic burden attributable to PN among MM patients in real-world practice settings in the US.

Methods: Adults diagnosed with MM and first treated (index event) between 1 July 2006 and 28 February 2017 were identified from MarketScan® Commercial and Medicare claim databases. Read More

MBio 2019 Apr 9;10(2). Epub 2019 Apr 9.

Division of Viral Products, Center for Biologics Evaluation and Research, FDA, Silver Spring, Maryland, USA

The effectiveness of influenza vaccines against circulating A(H1N1)pdm09 viruses was modest for several seasons despite the absence of antigenic drift of hemagglutinin (HA), the primary vaccine component. Since antibodies against HA and neuraminidase (NA) contribute independently to protection against disease, antigenic changes in NA may allow A(H1N1)pdm09 viruses to escape from vaccine-induced immunity. In this study, analysis of the specificities of human NA-specific monoclonal antibodies identified antigenic sites that have changed over time. Read More

Biochem Biophys Res Commun 2019 Apr 6. Epub 2019 Apr 6.

School of Medicine and Life Sciences, University of Jinan-Shandong Academy of Medical Sciences, Ji'nan, Shandong, China. Electronic address:

Wilson's disease (WD) is a rare autosomal recessive disorder of copper metabolism caused by an ATP7B gene mutation. Except for hepatic, neurological symptoms, lower bone mineral density is another most frequent clinical features of WD, but the underlying mechanisms have not been fully understood. This article aims to use induced pluripotent stem cells (iPSCs) to establish cellular osteoblasts model related to WD to identify abnormal osteogenesis and signaling pathways. Read More

J Hepatol 2019 Apr 6. Epub 2019 Apr 6.

Department of Biomedical Sciences of Cells and Systems, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands. Electronic address:

Background & Aims: Hepatocyte polarity is essential for the development of bile canaliculi and transport of bile and waste products such as copper safely out of the liver. Genetically inherited defects in polarized processes can cause severe diseases. Functional studies of autologous mutated proteins in the context of the polarized hepatocyte have been challenging because of the lack of appropriate cell models. Read More

JCI Insight 2019 Apr 9;5. Epub 2019 Apr 9.

Imatinib (Gleevec) reverses type 1 diabetes (T1D) in NOD mice and is currently in clinical trials in individuals with recent-onset disease. While research has demonstrated that imatinib protects islet β cells from the harmful effects of ER stress, the role the immune system plays in its reversal of T1D has been less well understood, and specific cellular immune targets have not been identified. In this study, we demonstrate that B lymphocytes, an immune subset that normally drives diabetes pathology, are unexpectedly required for reversal of hyperglycemia in NOD mice treated with imatinib. Read More

J Med Internet Res 2019 Apr 9;21(4):e12541. Epub 2019 Apr 9.

Durham Center of Innovation to Accelerate Discovery and Practice Transformation, Durham Veterans Affairs Health Care System, Durham, NC, United States.

Background: Patients with diabetes and poorly controlled hypertension are at increased risk for adverse renal and cardiovascular outcomes. Identifying these patients early and addressing modifiable risk factors is central to delaying renal complications such as diabetic kidney disease. Mobile health (mHealth), a relatively inexpensive and easily scalable technology, can facilitate patient-centered care and promote engagement in self-management, particularly for patients of lower socioeconomic status. Read More

Respir Med 2019 Apr 11;150:66-73. Epub 2019 Feb 11.

NIHR Southampton Respiratory Biomedical Research Centre, University Hospital Southampton, Southampton, UK; Clinical Experimental Sciences Unit, Faculty of Medicine, University of Southampton, University Hospital Southampton, South Academic Block, Southampton, UK. Electronic address:

Gastro-oesophageal reflux disease (GORD) has long been associated with poor asthma control without an established cause-effect relationship. 610 asthmatics (421 severe/88 mild-moderate) and 101 healthy controls were assessed clinically and a subset of 154 severe asthmatics underwent proteomic analysis of induced sputum using untargeted mass spectrometry, LC-IMS-MS. Univariate and multiple logistic regression analyses (MLR) were conducted to identify proteins associated with GORD in this cohort. Read More

Data (Basel) 2019 25;4(1):20. Epub 2019 Jan 25.

Bill and Melinda Gates Foundation, Seattle, WA 98109, USA;

Routine immunization coverage in Nigeria is suboptimal. In the northwestern state of Sokoto, an independent population-based survey for 2016 found immunization coverage with the third dose of Pentavalent vaccine to be 3%, whereas administrative coverage in 2016 was reported to be 69%. One possibility driving this large discrepancy is that administrative coverage is calculated using an under-estimated target population. Read More

HPB (Oxford) 2019 Apr 4. Epub 2019 Apr 4.

HPB Surgical Unit, Mater Hospital, Belfast BT14 6AB, UK.

Background: Research prioritisation can help identify clinically relevant questions and encourage high-quality, patient-centred research. Delphi methodology aims to develop consensus opinion within a group of experts, with recent Delphi projects helping to define the research agenda and funding within several medical and surgical specialties.

Methods: All members of the Association of Upper Gastrointestinal Surgeons (AUGIS) were asked to submit clinical research questions using an online survey (Phase 1). Read More

PLoS Med 2019 Apr 5;16(4):e1002776. Epub 2019 Apr 5.

TB Centre, London School of Hygiene & Tropical Medicine, London, United Kingdom.

Background: The prevalence of and mortality from HIV-associated tuberculosis (HIV/TB) in hospital inpatients in Africa remains unacceptably high. Currently, there is a lack of tools to identify those at high risk of early mortality who may benefit from adjunctive interventions. We therefore aimed to develop and validate a simple clinical risk score to predict mortality in high-burden, low-resource settings. Read More

PLoS One 2019 4;14(4):e0215133. Epub 2019 Apr 4.

Division of Neurosurgery, University of Toronto, Toronto, Ontario, Canada.

Degenerative cervical myelopathy (DCM) is a spinal cord condition that results in progressive non-traumatic compression of the cervical spinal cord. Spine surgeons must consider a large quantity of information relating to disease presentation, imaging features, and patient characteristics to determine if a patient will benefit from surgery for DCM. We applied a supervised machine learning approach to develop a classification model to predict individual patient outcome after surgery for DCM. Read More

JCI Insight 2019 Apr 4;4(7). Epub 2019 Apr 4.

Translational Tissue Engineering Center, Wilmer Eye Institute, and Department of Biomedical Engineering, Johns Hopkins University, Baltimore, Maryland, USA.

Senescent cells (SnCs) are increasingly recognized as central effector cells in age-related pathologies. Extracellular vesicles (EVs) are potential cellular communication tools through which SnCs exert central effector functions in the local tissue environment. To test this hypothesis in a medical indication that could be validated clinically, we evaluated EV production from SnCs enriched from chondrocytes isolated from human arthritic cartilage. Read More

Health Promot Pract 2019 Apr 3:1524839919839361. Epub 2019 Apr 3.

3 Brooklyn Health Disparities Center, Brooklyn, NY, USA.

Barbershop-based interventions have been increasingly implemented as a means to support culturally relevant and community-accessible health promotion and disease prevention efforts. Specifically, in neighborhoods of Brooklyn, New York, with high HIV seroprevalence rates, barbers have volunteered to support an initiative to help reduce sexual risk behavior. After implementing the Barbershop Talk With Brothers program for 5 years, we explored how program participation has affected barbers' HIV prevention and counseling skills to promote their clients' health, and assessed their views of next stages of the community-academic partnership, once the specific project ended. Read More

J Allergy Clin Immunol Pract 2019 Mar 30. Epub 2019 Mar 30.

Division of Allergy & Clinical Immunology, University of Virginia, Charlottesville, VA. Electronic address:

Background: Red meat allergy has historically been understood as a rare disease of atopic children but the discovery of the 'α-Gal syndrome', which relates to IgE to the oligosaccharide galactose-α-1,3-galactose (α-Gal), has challenged that notion.

Objective: To describe the clinical and immunologic characteristics of a large group of subjects with self-reported allergy to mammalian meat.

Methods: This was an observational study of 261 children and adults (range 5-82 years) who presented for evaluation for allergic reactions to mammalian meat. Read More

J Clin Oncol 2019 Apr 2:JCO1801994. Epub 2019 Apr 2.

14 Cornell University Medical College, New York, NY.

Purpose: Alliance/CALGB 50303 (NCT00118209), an intergroup, phase III study, compared dose-adjusted etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, and rituximab (DA-EPOCH-R) with standard rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) as frontline therapy for diffuse large B-cell lymphoma.

Patients And Methods: Patients received six cycles of DA-EPOCH-R or R-CHOP. The primary objective was progression-free survival (PFS); secondary clinical objectives included response rate, overall survival (OS), and safety. Read More

Circ Genom Precis Med 2019 Apr 2. Epub 2019 Apr 2.

Center for Human Genetic Research, Massachusetts General Hospital, Boston, MA.

Background: Familial hypobetalipoproteinemia (FHBL) is a genetic disorder caused by rare protein-truncating variants (PTV) in the gene encoding apolipoprotein B ( APOB), the major protein component of low-density and triglyceride-rich lipoprotein particles. Whether heterozygous APOB deficiency is associated with decreased risk for coronary heart disease (CHD) is uncertain. We combined family-based and large scale gene-sequencing to characterize the association of rare PTVs in APOB with circulating low-density lipoprotein cholesterol (LDL-C), triglycerides, and risk for CHD. Read More

NPJ Parkinsons Dis 2019 27;5. Epub 2019 Mar 27.

123andMe, Inc., 899W Evelyn Avenue, Mountain View, CA 94041 USA.

In order to systematically describe the Parkinson's disease phenome, we performed a series of 832 cross-sectional case-control analyses in a large database. Responses to 832 online survey-based phenotypes including diseases, medications, and environmental exposures were analyzed in 23andMe research participants. For each phenotype, survey respondents were used to construct a cohort of Parkinson's disease cases and age-matched and sex-matched controls, and an association test was performed using logistic regression. Read More

Dialogues Clin Neurosci 2018 12;20(4):341-345

Department of Neurosciences, College of Medicine and Philippine General Hospital, University of the Philippines, Manila; National Poison Management and Control Center, Philippine General Hospital, University of the Philippines, Manila, Philippines.

Wilson disease is a rare genetic disease causing pathologic deposition of copper in the liver, brain, cornea, kidney, and cardiac muscles. Presented are two cases of neurologic Wilson disease with progressive movement disorder and Kayser-Fleischer rings with low serum copper, low ceruloplasmin, and increased 24-hour urine copper against a background of normal transaminases. Cranial imaging revealed symmetric basal ganglia hyperintensities in T2/FLAIR. Read More