604,242 results match your criteria Disease Models & Mechanisms [Journal]


Utilization of the CRISPR-Cas9 Gene Editing System to Dissect Neuroinflammatory and Neuropharmacological Mechanisms in Parkinson's Disease.

J Neuroimmune Pharmacol 2019 Mar 16. Epub 2019 Mar 16.

Parkinson's Disorder Research Laboratory, Iowa Center for Advanced Neurotoxicology, Department of Biomedical Sciences, Iowa State University, Ames, IA, 50011, USA.

Chronic and debilitating neurodegenerative diseases, such as Parkinson's disease (PD), impose an immense medical, emotional, and economic burden on patients and society. Due to a complex interaction between genetic and environmental risk factors, the etiology of PD remains elusive. However, the cumulative evidence emerging from clinical and experimental research over the last several decades has identified mitochondrial dysfunction, oxidative stress, neuroinflammation, and dysregulated protein degradation as the main drivers of PD neurodegeneration. Read More

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http://dx.doi.org/10.1007/s11481-019-09844-3DOI Listing

Effects of NOP-Related Ligands in Nonhuman Primates.

Handb Exp Pharmacol 2019 Mar 17. Epub 2019 Mar 17.

Department of Physiology and Pharmacology, Wake Forest School of Medicine, Winston-Salem, NC, USA.

The nociceptin/orphanin FQ peptide (NOP) receptor-related ligands have been demonstrated in preclinical studies for several therapeutic applications. This article highlights (1) how nonhuman primates (NHP) were used to facilitate the development and application of positron emission tomography tracers in humans; (2) effects of an endogenous NOP ligand, nociceptin/orphanin FQ, and its interaction with mu opioid peptide (MOP) receptor agonists; and (3) promising functional profiles of NOP-related agonists in NHP as analgesics and treatment for substance use disorders. NHP models offer the most phylogenetically appropriate evaluation of opioid and non-opioid receptor functions and drug effects. Read More

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http://dx.doi.org/10.1007/164_2019_211DOI Listing

The association of sleep with metabolic pathways and metabolites: evidence from the Dietary Approaches to Stop Hypertension (DASH)-sodium feeding study.

Metabolomics 2019 Mar 16;15(4):48. Epub 2019 Mar 16.

Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, 9609 Medical Center Drive, Bethesda, MD, 20850, USA.

Introduction: Sleep is increasingly being viewed as an issue of public health concern, yet few epidemiologic studies have explored associations between sleep habits and metabolomic profile.

Objectives: To assess the association between sleep and blood metabolites.

Methods: We examined the association between sleep and 891 fasting plasma metabolites in a subgroup of 106 participants from the Dietary Approaches to Stop Hypertension (DASH)-Sodium feeding trial (1997-1999). Read More

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http://dx.doi.org/10.1007/s11306-019-1472-yDOI Listing

Long non-coding RNAs are emerging targets of phytochemicals for cancer and other chronic diseases.

Cell Mol Life Sci 2019 Mar 16. Epub 2019 Mar 16.

Department of Biochemistry, Institute of Science, Banaras Hindu University, Varanasi, Uttar Pradesh, 221005, India.

The long non-coding RNAs (lncRNAs) are the crucial regulators of human chronic diseases. Therefore, approaches such as antisense oligonucleotides, RNAi technology, and small molecule inhibitors have been used for the therapeutic targeting of lncRNAs. During the last decade, phytochemicals and nutraceuticals have been explored for their potential against lncRNAs. Read More

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http://dx.doi.org/10.1007/s00018-019-03053-0DOI Listing

Shift work, DNA methylation and epigenetic age.

Int J Epidemiol 2019 Mar 15. Epub 2019 Mar 15.

Epidemiology Branch, National Institute of Environmental Health Sciences, NIH, Research Triangle Park, NC, USA.

Background: Shift work has been associated with increased risk of age-related morbidity and mortality. Biological age, estimated using DNA methylation (DNAm), may quantify the biological consequences of shift work on the risk of age-related disease. We examined whether prior employment in shift-working occupations was associated with epigenetic age acceleration. Read More

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http://dx.doi.org/10.1093/ije/dyz027DOI Listing

Age independent survival benefit for patients with hepatocellular carcinoma (HCC) without metastases at diagnosis: a population-based study.

Gut 2019 Mar 16. Epub 2019 Mar 16.

Munich Cancer Registry, Institute for Medical Information Processing, Biometry and Epidemiology, Ludwig-Maximilians-University (LMU), Munich, Germany.

Objective: Hepatocellular carcinoma (HCC) is a major cause of death worldwide and its incidence is expected to increase globally. Aim of this study was to assess whether the implementation of screening policies and the improvement of treatment options translated into a real-world survival benefit in HCC patients.

Design: 4078 patients diagnosed with HCC between 1998 and 2016 from the Munich Cancer Registry were analysed. Read More

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http://dx.doi.org/10.1136/gutjnl-2018-318193DOI Listing

The association between cold spells and admissions of ischemic stroke in Hefei, China: Modified by gender and age.

Sci Total Environ 2019 Mar 1;669:140-147. Epub 2019 Mar 1.

Department of Epidemiology and Health Statistics, School of Public Health, Anhui Medical University, Hefei, Anhui 230032, China; Anhui Province Key Laboratory of Major Autoimmune Disease, China. Electronic address:

Background: Some studies have discovered that low ambient temperatures were associated with increased risk of the incidence of ischemic stroke. Although the frequency of extreme weather events is increasing, few studies have studied the effects of cold wave on ischemic stroke.

Objective: The purpose of this study was to explore the association between cold waves and ischemic stroke onset and further to explore how this association was modified by cold spell characteristics and individual-level factors. Read More

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http://dx.doi.org/10.1016/j.scitotenv.2019.02.452DOI Listing

Identifying periods of susceptibility to the impact of phthalates on children's cognitive abilities.

Environ Res 2019 Mar 5;172:604-614. Epub 2019 Mar 5.

Department of Epidemiology, Brown University, 121 South Main Street, Providence, RI, United States.

Background: Early-life phthalate exposures may adversely affect children's neurodevelopment by disrupting thyroid function, reducing gonadal hormone levels, or altering fatty acid concentrations in the brain. This study aimed to identify periods of heightened susceptibility during gestation, infancy, and childhood to the impact of phthalates on children's cognitive abilities.

Methods: We used data from 253 mother-child pairs in the Health Outcomes and Measures of the Environment (HOME) Study (Cincinnati, Ohio), a longitudinal pregnancy and birth cohort. Read More

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http://dx.doi.org/10.1016/j.envres.2019.03.009DOI Listing

The contralateral knee may not be a valid control for biomechanical outcomes after unilateral total knee arthroplasty.

Gait Posture 2019 Mar 8;70:179-184. Epub 2019 Mar 8.

Rutgers, The State University of New Jersey, School of Health Professions, Department of Rehabilitation and Movement Sciences, Physical Therapy Program North, 65 Bergen Street - Office 714A, Newark, NJ, 07107, USA.

Background: Although unilateral symptoms and unilateral total knee arthroplasty (TKA) are common, many patients have bilateral radiographic osteoarthritis (OA). Because the contralateral (non-operated) limb is often used as a comparison for clinical and biomechanical outcomes, it is important to know if the presence of OA influences movement patterns in either limb.

Research Question: The purpose of this study was to compare bilateral sagittal plane biomechanics between subjects with and without contralateral knee OA after unilateral TKA. Read More

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http://dx.doi.org/10.1016/j.gaitpost.2019.01.030DOI Listing

T-cell mediated adaptive immunity and antibody-dependent enhancement in secondary dengue infection.

J Theor Biol 2019 Mar 13. Epub 2019 Mar 13.

Faculty of Advanced Life Science, Hokkaido University, Sapporo, Hokkaido, 060-0810, Japan; PRESTO, Japan Science and Technology Agency, Saitama, 332-0012, Japan. Electronic address:

Dengue infection results in a significant number of deaths, mostly in the tropical and subtropical regions across the world. Yet, despite the seriousness of this disease, vaccine, and antiviral drugs that could be employed in dengue treatment remain elusive. The desire to establish the factors determining the disease severity and the growing need for efficient drugs has prompted extensive research interest in within-host viral dynamics. Read More

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http://dx.doi.org/10.1016/j.jtbi.2019.03.010DOI Listing

Fighting rheumatoid arthritis: Kv1.3 as a therapeutic target.

Biochem Pharmacol 2019 Mar 13. Epub 2019 Mar 13.

Molecular Physiology Laboratory, Departament de Bioquímica i Biomedicina Molecular, Institut de Biomedicina Universitat de Barcelona (IBUB), Barcelona, Spain. Electronic address:

Rheumatoid arthritis (RA) is a serious autoimmune disease that has severe impacts on both the wellbeing of patients and the economy of the health system. Similar to many autoimmune diseases, RA concurs with a long evolution, which eventually results in highly debilitating symptoms. Therapeutic treatments last for long periods during RA. Read More

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http://dx.doi.org/10.1016/j.bcp.2019.03.016DOI Listing

Microglia Specific Metabolic Changes in Neurodegeneration.

Authors:
Blanca I Aldana

J Mol Biol 2019 Mar 13. Epub 2019 Mar 13.

Department of Drug Design and Pharmacology, Faculty of Health and Medical Sciences. University of Copenhagen, Universitetsparken 2, 2100, Copenhagen, Denmark. Electronic address:

The high energetic demand of the brain deems this organ rather sensitive to changes in energy supply. Therefore, even minor alterations in energy metabolism may underlie detrimental disturbances in brain function, contributing to the generation and progression of neurodegenerative diseases. Considerable evidence supports the key role of deficits in cerebral energy metabolism, particularly hypometabolism of glucose and mitochondrial dysfunction, in the pathophysiology of brain disorders. Read More

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http://dx.doi.org/10.1016/j.jmb.2019.03.006DOI Listing

DDOT: A Swiss Army Knife for Investigating Data-Driven Biological Ontologies.

Cell Syst 2019 Mar 11. Epub 2019 Mar 11.

Department of Medicine, University of California, San Diego, La Jolla, CA 92093, USA; Graduate Program in Bioinformatics and Systems Biology, University of California, San Diego, La Jolla, CA 92093, USA; Department of Bioengineering, University of California, San Diego, La Jolla, CA 92093, USA. Electronic address:

Systems biology requires not only genome-scale data but also methods to integrate these data into interpretable models. Previously, we developed approaches that organize omics data into a structured hierarchy of cellular components and pathways, called a "data-driven ontology." Such hierarchies recapitulate known cellular subsystems and discover new ones. Read More

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http://dx.doi.org/10.1016/j.cels.2019.02.003DOI Listing

Model-based hearing diagnostics based on wideband tympanometry measurements utilizing fuzzy arithmetic.

Hear Res 2019 Feb 28. Epub 2019 Feb 28.

Reutlingen University, Alteburgstr. 150, 72762, Reutlingen, Germany.

Today's audiometric methods for the diagnosis of middle ear disease are often based on a comparison of measurements with standard curves, that represent the statistical range of normal hearing responses. Because of large inter-individual variances in the middle ear, especially in wideband tympanometry (WBT), specificity and quantitative evaluation are greatly restricted. A new model-based approach could transform today's predominantly qualitative hearing diagnostics into a quantitative and tailored, patient-specific diagnosis, by evaluating WBT measurements with the aid of a middle-ear model. Read More

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http://dx.doi.org/10.1016/j.heares.2019.02.011DOI Listing
February 2019

The relationships between democratic experience, adult health, and cause-specific mortality in 170 countries between 1980 and 2016: an observational analysis.

Lancet 2019 Mar 13. Epub 2019 Mar 13.

Department of Philosophy, Bilkent University, Ankara, Turkey.

Background: Previous analyses of democracy and population health have focused on broad measures, such as life expectancy at birth and child and infant mortality, and have shown some contradictory results. We used a panel of data spanning 170 countries to assess the association between democracy and cause-specific mortality and explore the pathways connecting democratic rule to health gains.

Methods: We extracted cause-specific mortality and HIV-free life expectancy estimates from the Global Burden of Diseases, Injuries, and Risk Factors Study 2016 and information on regime type from the Varieties of Democracy project. Read More

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http://dx.doi.org/10.1016/S0140-6736(19)30235-1DOI Listing

Matrix metalloproteinase-7 protects against acute kidney injury by priming renal tubules for survival and regeneration.

Kidney Int 2019 Mar 8. Epub 2019 Mar 8.

Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA; State Key Laboratory of Organ Failure Research, National Clinical Research Center of Kidney Disease, Division of Nephrology, Nanfang Hospital, Southern Medical University, Guangzhou, China. Electronic address:

Matrix metalloproteinase-7 (MMP-7) is a secreted endopeptidase that degrades a broad range of substrates. Recent studies have identified MMP-7 as an early biomarker to predict severe acute kidney injury (AKI) and poor outcomes after cardiac surgery; however, the role of MMP-7 in the pathogenesis of AKI is unknown. In this study, we investigated the expression of MMP-7 and the impact of MMP-7 deficiency in several models of AKI. Read More

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http://dx.doi.org/10.1016/j.kint.2018.11.043DOI Listing

Modification of sequential organ failure assessment score using acute kidney injury classification.

J Crit Care 2019 Feb 26;51:198-203. Epub 2019 Feb 26.

Department of Emergency and Critical Care Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, Japan. Electronic address:

Purpose: To assess the predictive validity of a modified Sequential Organ Failure Assessment (SOFA) score, of which the renal component was replaced with Kidney Disease Improving Global Outcomes (KDIGO) classification of Acute Kidney Injury (AKI).

Materials And Methods: Using a prospective cohort study on AKI in Japan, we replaced the renal component of SOFA score with AKI stages according to the KDIGO criteria except that initiation of renal replacement therapy was assigned four points. We assessed the predictive validity of KDIGO-based SOFA score for hospital and ICU mortality by comparing the areas under the receiver operating characteristic curve (AUC) derived from logistic regression models with that of the original SOFA score. Read More

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http://dx.doi.org/10.1016/j.jcrc.2019.02.026DOI Listing
February 2019

Experimental models to study prion disease pathogenesis and identify potential therapeutic compounds.

Curr Opin Pharmacol 2019 Mar 13;44:28-38. Epub 2019 Mar 13.

Istituto di Ricerche Farmacologiche Mario Negri IRCCS, 20156 Milan, Italy. Electronic address:

Prion diseases are devastating neurodegenerative disorders for which no drugs are available. The successful development of therapeutics depends on drug screening platforms and preclinical models that recapitulate key molecular and pathological features of the disease. Innovative experimental tools have been developed over the last few years that might facilitate drug discovery, including cell-free prion replication assays and prion-infected flies. Read More

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http://dx.doi.org/10.1016/j.coph.2019.02.002DOI Listing

Development of Muscina stabulans at constant temperatures with implications for minimum postmortem interval estimation.

Forensic Sci Int 2019 Mar 5;298:71-79. Epub 2019 Mar 5.

Department of Forensic Medicine, Soochow University, Ganjiang East Road, Suzhou, China. Electronic address:

Muscina stabulans (Fallén 1817) is a disease vector and a species of forensic value, particularly in the case of buried bodies. In this study, M. stabulans was reared under a total of seven constant temperatures at 16-34 °C, and the developmental duration, accumulated degree days, and larval body length were studied. Read More

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http://dx.doi.org/10.1016/j.forsciint.2019.02.051DOI Listing

Metabolome-based signature of disease pathology in MS.

Mult Scler Relat Disord 2019 Mar 9;31:12-21. Epub 2019 Mar 9.

Discovery MS, David H. Murdock Research Institute, 150 Research Campus Drive, Kannapolis, NC 28081, United States; Duke Molecular Physiology Institute, 300 North Duke Street, Duke University, Durham, NC 27701, United States. Electronic address:

Background: Diagnostic delays are common for multiple sclerosis (MS) since diagnosis typically depends on the presentation of nonspecific clinical symptoms together with radiologically-determined central nervous system (CNS) lesions. It is important to reduce diagnostic delays as earlier initiation of disease modifying therapies mitigates long-term disability. Developing a metabolomic blood-based MS biomarker is attractive, but prior efforts have largely focused on specific subsets of metabolite classes or analytical platforms. Read More

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http://dx.doi.org/10.1016/j.msard.2019.03.006DOI Listing

LncRNA analysis of lung tissues after hUC-MSCs and FTY720 treatment of lipopolysaccharide-induced acute lung injury in mouse models.

Int Immunopharmacol 2019 Mar 13;71:68-75. Epub 2019 Mar 13.

Academy of Military Medical Sciences, Beijing 100850, China.

Acute lung injury (ALI), a persistent lung inflammatory response syndrome, may evolve into acute respiratory distress syndrome (ARDS). Characterized by rapid onset, critical features, and a complex etiology, ALI remains a challenging critical respiratory disease. Recently, mesenchymal stem cells (MSCs) have provided a new solution for the treatment of ALI. Read More

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http://dx.doi.org/10.1016/j.intimp.2019.03.017DOI Listing

Artificial intelligence based discovery of the association between depression and chronic fatigue syndrome.

J Affect Disord 2019 Mar 8;250:380-390. Epub 2019 Mar 8.

Beijing University of Chinese Medicine, Beijing 100029, China. Electronic address:

Background: Both of the modern medicine and the traditional Chinese medicine classify depressive disorder (DD) and chronic fatigue syndrome (CFS) to one type of disease. Unveiling the association between depressive and the fatigue diseases provides a great opportunity to bridge the modern medicine with the traditional Chinese medicine.

Methods: In this work, 295 general participants were recruited to complete Zung Self-Rating Depression Scales and Chalder Fatigue Scales, and meanwhile, to donate plasma and urine samples for H NMR-metabolic profiling. Read More

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http://dx.doi.org/10.1016/j.jad.2019.03.011DOI Listing

[Bioinks and in vitro neurovascular unit production - New prospects in Alzheimer's disease research].

Hell J Nucl Med 2019 Jan-Apr;22 Suppl:209-222

Laboratory of Biochemistry, Dept. of Chemistry, Aristotle University, 54124, Thessaloniki, Greece.

Neurovascular dysfunction is a central process in the pathogenesis of the stroke and most neurodegenerative diseases, including Alzheimer's disease. The multi-cell neurovascular unit (NVU) combines the components of the neural, vascular and extracellular matrix (ECM) into an important interface whose proper function is critical to maintaining brain health. Tissue engineering now offers new tools and information to promote understanding of NVU's operation. Read More

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January 2019

[Technical characteristics of Alzheimer model based on organ technology (organoid)].

Hell J Nucl Med 2019 Jan-Apr;22 Suppl:195-208

Laboratory of Biochemistry, Dept. of Chemistry, Aristotle University, 54124, Thessaloniki, Greece.

Alzheimer's disease (AD) is a serious neurodegenerative disorder that manifests itself as progressive damage to memory and knowledge and is the main cause of dementia in the elderly. AD is characterized by extracellular deposition of amyloid-β plate (Aβ) and by the formation of neurofibrillary tangles, composed of hyperphosphorylated Tau protein. These modifications lead to neuronal cell death, vascular dysfunction and inflammatory disorders. Read More

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January 2019
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Association of Visit-to-Visit Variability of Blood Pressure with Cardiovascular Disease among Type 2 Diabetes Mellitus Patients: A Cohort Study.

Diabetes Metab J 2019 Mar 6. Epub 2019 Mar 6.

Department of Epidemiology and Health Statistics, Zhejiang University School of Public Health, Hangzhou, China.

Background: Increasing evidence has shown that visit-to-visit variability (VVV) of blood pressure (BP) is associated with an increased risk of cardiovascular disease (CVD). The objective of this study was to evaluate the impact of VVV of systolic blood pressure (SBP) and diastolic blood pressure (DBP) on the risk of CVD among patients with type 2 diabetes mellitus (T2DM) in China.

Methods: We conducted a retrospective cohort study of 10,163 T2DM patients who were not previously diagnosed with CVD from January 2008 to December 2012 in Ningbo, China. Read More

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http://dx.doi.org/10.4093/dmj.2018.0108DOI Listing

Dipeptidyl Peptidase-4 Inhibitors versus Other Antidiabetic Drugs Added to Metformin Monotherapy in Diabetic Retinopathy Progression: A Real World-Based Cohort Study.

Diabetes Metab J 2019 Feb 20. Epub 2019 Feb 20.

Department of Endocrinology and Metabolism, Ajou University School of Medicine, Suwon, Korea.

Background: To investigate the effects of dipeptidyl peptidase-4 inhibitor (DPP4i) as add-on medications to metformin on progression of diabetic retinopathy (DR) in patients with type 2 diabetes mellitus, compared with sulfonylurea (SU) or thiazolidinedione (TZD).

Methods: We identified 4,447 patients with DPP4i, 6,136 with SU, and 617 with TZD in addition to metformin therapy from the database of Korean National Health Insurance Service between January 2013 and December 2015. Cox proportional hazards regression models were used to calculate hazard ratios (HRs) for DR progression. Read More

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http://dx.doi.org/10.4093/dmj.2018.0137DOI Listing
February 2019

Impact of Longitudinal Changes in Metabolic Syndrome Status over 2 Years on 10-Year Incident Diabetes Mellitus.

Diabetes Metab J 2019 Feb 20. Epub 2019 Feb 20.

Department of Internal Medicine, Yonsei University Wonju College of Medicine, Wonju, Korea.

Background: Metabolic syndrome (MetS) is a known predictor of diabetes mellitus (DM), but whether longitudinal changes in MetS status modify the risk for DM remains unclear. We investigated whether changes in MetS status over 2 years modify the 10-year risk of incident DM.

Methods: We analyzed data from 7,317 participants aged 40 to 70 years without DM at baseline, who took part in 2001 to 2011 Korean Genome Epidemiology Study. Read More

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http://dx.doi.org/10.4093/dmj.2018.0111DOI Listing
February 2019

Modeling Neisseria meningitidis Infection in Mice: Methods and Logistical Considerations for Nasal Colonization and Invasive Disease.

Methods Mol Biol 2019 ;1969:149-168

Department of Molecular Genetics, University of Toronto, Toronto, ON, Canada.

The single greatest barrier to studying the lifestyle of Neisseria meningitidis stems from its exquisite adaptation to life in humans, a specialization which prevents it from infecting other animals. This barrier to modeling meningococcal infection has been overcome by the provision of factors that allow the meningococci to overcome one or more aspects of host restriction, including the use of mice expressing receptors that allow mucosal colonization and/or the inclusion of serum factors that facilitate meningococcal replication during disseminated meningococcal disease. Here we discuss these advances, consider variables that influence the outcome of infection, and detail the technical requirements to establish robust and reproducible nasal colonization or sepsis. Read More

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http://dx.doi.org/10.1007/978-1-4939-9202-7_11DOI Listing
January 2019

In Vitro Models for Studying the Interaction of Neisseria meningitidis with Human Brain Endothelial Cells.

Methods Mol Biol 2019 ;1969:135-148

Institute for Hygiene and Microbiology, University of Würzburg, Würzburg, Germany.

Bacterial meningitis is a serious, life-threatening infection of the central nervous system (CNS). To cause meningitis, bacteria must interact with and penetrate the meningeal blood-cerebrospinal fluid barrier (mB/CSFB), which comprises highly specialized brain endothelial cells. Neisseria meningitidis (meningococcus) is a leading cause of bacterial meningitis, and examination meningococcus' interaction with the BBB is critical for understanding disease progression. Read More

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http://dx.doi.org/10.1007/978-1-4939-9202-7_10DOI Listing
January 2019

Pre-existing autoimmune disease and the risk of immune-related adverse events among patients receiving checkpoint inhibitors for cancer.

Cancer Immunol Immunother 2019 Mar 15. Epub 2019 Mar 15.

Division of Population Sciences, Dana-Farber Cancer Institute, 450 Brookline Ave., Boston, MA, 02215, USA.

Introduction: Patients with pre-existing autoimmune diseases have been excluded from clinical trials of immune checkpoint inhibitors (ICIs) for cancer. Real-world evidence is necessary to understand ICI safety in this population.

Methods: Patients treated with ICIs from 2011 to 2017 were identified using data from a large health insurer. Read More

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http://link.springer.com/10.1007/s00262-019-02321-z
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http://dx.doi.org/10.1007/s00262-019-02321-zDOI Listing
March 2019
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Post-"Modern Epidemiology": when methods meet matter.

Am J Epidemiol 2019 Mar 16. Epub 2019 Mar 16.

Medical Research Council Integrative Epidemiology Unit, Bristol Medical School, University of Bristol, UK.

In the last third of the 20th century aetiological epidemiology within high-income country academia shifted its primary concern from attempting to tackle the apparent epidemic of "non-communicable disease" to an increasing focus on developing statistical and causal inference methodologies. This move was mutually constitutive with the failure of applied epidemiology to make major progress, with many of the advances in understanding the causes of "non-communicable diseases" coming from outside the discipline, whilst ironically revealing the infectious origins of several major conditions. Conversely, there were many examples of epidemiological studies promoting ineffective interventions, and little evident attempt to account for such failure. Read More

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http://dx.doi.org/10.1093/aje/kwz064DOI Listing

The Association of Occupational Psychosocial Factors with the Prevalence of Irritable Bowel Syndrome in the Chilean Working Population.

Ann Work Expo Health 2019 Mar 16. Epub 2019 Mar 16.

Department of Public Health, University of Massachusetts Lowell, Lowell MA, USA.

Background: Irritable bowel syndrome (IBS) is a stress-related disease linked to psychosocial factors, though knowledge about its occupational psychosocial aspects is scarce.

Objective: A cross-sectional study of the prevalence of IBS and its association with occupational psychosocial factors in Chilean workers was conducted.

Methods: IBS prevalence, using the IBS-Rome IV criteria, in the working population was estimated using data from the National Health Survey of 2009. Read More

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http://dx.doi.org/10.1093/annweh/wxz017DOI Listing

Emerging Challenges and Opportunities in Infectious Disease Epidemiology.

Am J Epidemiol 2019 Mar 16. Epub 2019 Mar 16.

Division of Epidemiology and Biostatistics, School of Public Health, University of California, Berkeley, Berkeley, California.

Much of the intellectual tradition of modern epidemiology stems from efforts to understand and combat chronic diseases persisting through the 20th century epidemiologic transition of countries such as the United States and United Kingdom. Following decades of relative obscurity, infectious disease epidemiology has undergone an intellectual rebirth in recent years amid increasing recognition of the threat posed by both new and familiar pathogens. Here we review the emerging coalescence of infectious disease epidemiology around a core set of study designs and statistical methods bearing little resemblance to the chronic disease epidemiology toolkit. Read More

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https://academic.oup.com/aje/advance-article/doi/10.1093/aje
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http://dx.doi.org/10.1093/aje/kwy264DOI Listing
March 2019
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Systems modeling to advance the promise of data science in epidemiology.

Am J Epidemiol 2019 Mar 16. Epub 2019 Mar 16.

Department of Epidemiology, Columbia University Mailman School of Public Health, New York, New York.

Systems science models use computer-based algorithms to model dynamic interactions between study units within and across levels, and are characterized by non-linear and feedback processes. They are particularly valuable approaches to complement the traditional epidemiologic toolbox in cases when real data is not available, and in cases when traditional epidemiologic methods are limited by issues such as interference, spatial dependence, and dynamic feedback processes. This commentary proposes two key contributions that systems models can make to epidemiology: (1) by testing assumptions about underlying mechanisms that give rise to population distributions of disease; and (2) by helping us identify the types of interventions that have the greatest potential to reduce population rates of disease in the future, or in new sites where they have not yet been implemented. Read More

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http://dx.doi.org/10.1093/aje/kwy262DOI Listing

Implications of the local haemodynamic forces on the phenotype of coronary plaques.

Heart 2019 Mar 15. Epub 2019 Mar 15.

Department of Cardiology, Bern University Hospital, Bern, Switzerland.

Aim: To examine the effect of endothelial shear stress (ESS) on the dynamic changes in plaque phenotype.

Methods: Patients with myocardial infarction that had intravascular ultrasound-virtual histology (IVUS-VH) and optical coherence tomography (OCT) at baseline and 13-month follow-up were studied. The IVUS-VH data were used to reconstruct the nonculprit vessels, and in the obtained models the ESS was estimated in 3 mm segments. Read More

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http://dx.doi.org/10.1136/heartjnl-2018-314086DOI Listing

Review of the scientific evolution of gene therapy for the treatment of homozygous familial hypercholesterolaemia: past, present and future perspectives.

J Med Genet 2019 Mar 15. Epub 2019 Mar 15.

Vascular Medicine and Metabolism Unit, Research Unit on Lipids and Atherosclerosis, 'Sant Joan' University Hospital, Universitat Rovira i Virgili, Institut de Investigació Sanitaria Pere Virgili (IISPV), Spanish Biomedical Research Centre in Diabetes and Associated Metabolic Disorders (CIBERDEM), Reus, Spain.

Familial hypercholesterolaemia (FH) is a devastating genetic disease that leads to extremely high cholesterol levels and severe cardiovascular disease, mainly caused by mutations in any of the main genes involved in low-density lipoprotein cholesterol (LDL-C) uptake. Among these genes, mutations in the LDL receptor () are responsible for 80%-90% of the FH cases. The severe homozygous variety (HoFH) is not successfully treated with standard cholesterol-lowering therapies, and more aggressive strategies must be considered to mitigate the effects of this disease, such as weekly/biweekly LDL apheresis. Read More

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http://dx.doi.org/10.1136/jmedgenet-2018-105713DOI Listing

The Association of Toll-Like Receptor 4 Gene Polymorphisms with Primary Open Angle Glaucoma Susceptibility: A meta-analysis.

Biosci Rep 2019 Mar 15. Epub 2019 Mar 15.

Faculty of Optometry, Ramkhamhaeng University, Bangkok, Thailand, Bangkok, Thailand

Primary Open Angle Glaucoma (POAG) and normal tension glaucoma (NTG) cause irreversible blindness, while current medications cannot completely inhibit disease progression. An understanding of immunopathogenesis is thus a keystone to develop novel drug targets and genetic markers are still required for early diagnosis. Toll-like receptor 4 (TLR4) is an essential player in inflammation in various diseases. Read More

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http://dx.doi.org/10.1042/BSR20190029DOI Listing

Immigrant and Refugee Explanatory Models of Chronic Disease: Provider "Learning Up" for Culturally Responsive Care.

N C Med J 2019 Mar-Apr;80(2):113-115

associate professor, Department of Public Health Education, University of North Carolina at Greensboro, Greensboro, North Carolina

Immigrant and refugee populations in North Carolina bring with them traditionally based explanatory models (EMs) of disease that influence health care interactions. Providers who encounter these models are often challenged with how best to leverage them for prevention outreach and care. Participation in "learning up" opportunities increases provider awareness and capacity for cultural responsiveness when dealing with immigrant and refugee clients. Read More

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http://dx.doi.org/10.18043/ncm.80.2.113DOI Listing

Advances in molecular and cell biology of dystonia: Focus on torsinA.

Neurobiol Dis 2019 Mar 12;127:233-241. Epub 2019 Mar 12.

Department of Neurology, the University of Pennsylvania, Philadelphia, PA, USA; Raymond G. Perelman Center for Cellular and Molecular Therapy, The Children's Hospital of Philadelphia, Philadelphia, PA, USA. Electronic address:

During the last two decades, our knowledge on the genetic bases of Mendelian forms of dystonia has expanded significantly. This has translated into the generation of multiple cell and animal models to explore the neurobiological bases of this hyperkinetic movement disorder. A majority of these studies have focused on DYT1 dystonia, caused by dominant mutations in the gene encoding for the protein torsinA. Read More

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http://dx.doi.org/10.1016/j.nbd.2019.03.007DOI Listing

Intestinal microbiome as a novel therapeutic target for local and systemic inflammation.

Pharmacol Ther 2019 Mar 12. Epub 2019 Mar 12.

Molecular Gastroenterology and Hepatology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto 602-8566, Japan; Department for Medical Innovation and Translational Medical Science, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto 602-8566, Japan.

Recently, the pathogenesis of systemic inflammatory disease such as inflammatory bowel disease (IBD), multiple sclerosis (MS), systemic inflammatory arthritis, asthma, and non-alcoholic fatty liver disease has been reported to be related to the dysbiosis of gut microbiota. The contribution of special bacteria for the development of those diseases has been elucidated by disease animal models such as germ-free mice. Besides, the contribution by several bacteria for the pathogenesis of those diseases has been suggested by detailed analysis of the 16 small ribosomal subunit RNA (16S rRNA) from stool samples of the patients. Read More

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https://linkinghub.elsevier.com/retrieve/pii/S01637258193004
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http://dx.doi.org/10.1016/j.pharmthera.2019.03.006DOI Listing
March 2019
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Prognostic markers at adolescence in patients Biliary Atresia for liver transplantation in adulthood.

J Hepatol 2019 Mar 12. Epub 2019 Mar 12.

Paediatric Liver, GI and Nutrition Centre and Mowatlabs, Kings College Hospital, London, UK.

Background & Aims: Native liver survival (NLS) for Biliary Atresia (BA) into adulthood, has been reported as 14-44% worldwide. Complications related to portal hypertension (PHT) and cholangitis are common in adulthood. For those requiring liver transplantation (LT), the timing can be challenging. Read More

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http://dx.doi.org/10.1016/j.jhep.2019.03.005DOI Listing

Unsupervised quantification of tissue immunofluorescence in animal models of multiple sclerosis - instructions for use.

J Neurosci Methods 2019 Mar 12. Epub 2019 Mar 12.

Department of Neurology, Goethe University Hospital, Frankfurt am Main, Germany.

Background: In the analysis of animal models of CNS diseases such as experimental autoimmune encephalomyelitis (EAE), immunostaining and histopathology are important readouts. However, the complex morphological features of a tissue staining are often reduced to a single measure which relies on tedious manual planimetry. Furthermore, the measure itself and co-variables such as the region being analysed are chosen in a human decision-making process, which introduces bias. Read More

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http://dx.doi.org/10.1016/j.jneumeth.2019.03.003DOI Listing

Retinoic Acid Induces Hyperactivity, and Blocking Its Receptor Unmasks Light Responses and Augments Vision in Retinal Degeneration.

Neuron 2019 Mar 8. Epub 2019 Mar 8.

Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA 94720, USA; Vision Science Graduate Group, University of California, Berkeley, Berkeley, CA 94720, USA. Electronic address:

Light responses are initiated in photoreceptors, processed by interneurons, and synaptically transmitted to retinal ganglion cells (RGCs), which send information to the brain. Retinitis pigmentosa (RP) is a blinding disease caused by photoreceptor degeneration, depriving downstream neurons of light-sensitive input. Photoreceptor degeneration also triggers hyperactive firing of RGCs, obscuring light responses initiated by surviving photoreceptors. Read More

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http://dx.doi.org/10.1016/j.neuron.2019.02.015DOI Listing

Belief about seat belt use and seat belt wearing behavior among front and rear seat passengers in the United States.

J Safety Res 2019 Feb 14;68:81-88. Epub 2018 Dec 14.

Centers for Disease Control & Prevention (CDC), National Center for Injury Prevention & Control (NCIPC), 4770 Buford Highway, Atlanta, GA 30341, USA. Electronic address:

Introduction: Unrestrained drivers and passengers represent almost half of all passenger vehicle occupant deaths in the United States. The current study assessed the relationship between the belief about importance of seat belt use and the behavior of always wearing a seat belt.

Method: Data from 2012 ConsumerStyles were analyzed separately for front and rear passenger seating positions. Read More

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https://linkinghub.elsevier.com/retrieve/pii/S00224375183069
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http://dx.doi.org/10.1016/j.jsr.2018.12.007DOI Listing
February 2019
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Molecular markers and potential therapeutic targets in non-WNT/non-SHH (group 3 and group 4) medulloblastomas.

J Hematol Oncol 2019 Mar 15;12(1):29. Epub 2019 Mar 15.

2nd Department of Pediatrics, Semmelweis University, Tűzoltó u. 7-9, Budapest, H-1094, Hungary.

Childhood medulloblastomas (MB) are heterogeneous and are divided into four molecular subgroups. The provisional non-wingless-activated (WNT)/non-sonic hedgehog-activated (SHH) category combining group 3 and group 4 represents over two thirds of all MBs, coupled with the highest rates of metastases and least understood pathology. The molecular era expanded our knowledge about molecular aberrations involved in MB tumorigenesis, and here, we review processes leading to non-WNT/non-SHH MB formations. Read More

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http://dx.doi.org/10.1186/s13045-019-0712-yDOI Listing

Efficient genome engineering of Toxoplasma gondii using the TALEN technique.

Parasit Vectors 2019 Mar 15;12(1):112. Epub 2019 Mar 15.

Department of Pathogen Biology, Guangdong Provincial Key Laboratory of Tropical Disease Research, School of Public Health, Southern Medical University, Guangzhou, 510515, China.

Background: Aromatic amino acid hydroxylase 2 (AAH2) is a bradyzoite-specific upregulated protein that may alter host behaviour by altering the host dopaminergic pathway. To better understand the role of the parasite's AAH2 in host-parasite interactions, we generated an AAH2 fluorescent marker strain of T. gondii using the TALEN technique. Read More

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http://dx.doi.org/10.1186/s13071-019-3378-yDOI Listing

The effect of repeated remote ischemic postconditioning on infarct size in patients with an ischemic stroke (REPOST): study protocol for a randomized clinical trial.

Trials 2019 Mar 15;20(1):167. Epub 2019 Mar 15.

Department of Physiology, Radboud University Medical Centre, Radboud Institute for Health Sciences, Geert Grooteplein Zuid 10, 6525GA, Nijmegen, Gelderland, Netherlands.

Background: Remote ischemic postconditioning (rIPostC) refers to the observation that repeated, short periods of ischemia protect remote areas against tissue damage during and after prolonged ischemia. Based on previous observations of a potential neuroprotective effect of rIPostC, the aim of this study is to evaluate whether repeated rIPostC after an ischemic stroke can reduce infarct size, which could be translated to an improvement in clinical outcomes.

Methods/design: We will enroll 200 ischemic stroke patients to daily rIPostC or sham conditioning during hospitalization into a randomized single-blind placebo-controlled trial. Read More

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http://dx.doi.org/10.1186/s13063-019-3264-0DOI Listing

Population genomic and evolutionary modelling analyses reveal a single major QTL for ivermectin drug resistance in the pathogenic nematode, Haemonchus contortus.

BMC Genomics 2019 Mar 15;20(1):218. Epub 2019 Mar 15.

Department of Comparative Biology and Experimental Medicine, Faculty of Veterinary Medicine, University of Calgary, Calgary, Alberta, Canada.

Background: Infections with helminths cause an enormous disease burden in billions of animals and plants worldwide. Large scale use of anthelmintics has driven the evolution of resistance in a number of species that infect livestock and companion animals, and there are growing concerns regarding the reduced efficacy in some human-infective helminths. Understanding the mechanisms by which resistance evolves is the focus of increasing interest; robust genetic analysis of helminths is challenging, and although many candidate genes have been proposed, the genetic basis of resistance remains poorly resolved. Read More

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http://dx.doi.org/10.1186/s12864-019-5592-6DOI Listing

Gout is associated with a higher risk of chronic renal disease in older adults: a retrospective cohort study of U.S. Medicare population.

BMC Nephrol 2019 Mar 15;20(1):93. Epub 2019 Mar 15.

Department of Medicine at School of Medicine, University of Alabama at Birmingham, 1720 Second Ave. South, Birmingham, AL, 35294-0022, USA.

Background: Hyperuricemia and gout have been linked to chronic kidney disease (CKD). Whether the increased risk of CKD in gout is due to shared risk factors such as hypertension, diabetes or heart disease, or due to gout itself is not known. Studies in older adults, who tend to have a high incidence of CKD, are limited. Read More

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http://dx.doi.org/10.1186/s12882-019-1274-5DOI Listing

MMP-8-Responsive Polyethylene Glycol Hydrogel for Intraoral Drug Delivery.

J Dent Res 2019 Mar 15:22034519831931. Epub 2019 Mar 15.

1 The State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) and Key Laboratory for Oral Biomedical Ministry of Education, School and Hospital of Stomatology, Wuhan University, Wuhan, China.

Currently available drug delivery systems for oral diseases suffer from short retention time and poor local concentrations at the target site. A biodegradable stimulus-responsive hydrogel was synthesized in the present study to evaluate its application as an environmentally sensitive carrier for on-demand intraoral drug delivery. The hydrogel was synthesized from diacrylate-containing polyethylene glycol-based scaffolds and a cysteine-terminated peptide crosslinker (CGPQG↓IWGQC) via a Michael-type addition reaction. Read More

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http://dx.doi.org/10.1177/0022034519831931DOI Listing
March 2019
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