International Veterinary Epilepsy Task Force Consensus Proposal: Diagnostic approach to epilepsy in dogs

This article outlines the consensus proposal on diagnosis of epilepsy in dogs by the International Veterinary Epilepsy Task Force. The aim of this consensus proposal is to improve consistency in the diagnosis of epilepsy in the clinical and research settings. The diagnostic approach to the patient presenting with a history of suspected epileptic seizures incorporates two fundamental steps: to establish if the events the animal is demonstrating truly represent epileptic seizures and if so, to identify their underlying cause. Differentiation of epileptic seizures from other non-epileptic episodic paroxysmal events can be challenging. Criteria that can be used to make this differentiation are presented in detail and discussed. Criteria for the diagnosis of idiopathic epilepsy (IE) are described in a three-tier system. Tier I confidence level for the diagnosis of IE is based on a history of two or more unprovoked epileptic seizures occurring at least 24 h apart, age at epileptic seizure onset of between six months and six years, unremarkable inter-ictal physical and neurological examination, and no significant abnormalities on minimum data base blood tests and urinalysis. Tier II confidence level for the diagnosis of IE is based on the factors listed in tier I and unremarkable fasting and post-prandial bile acids, magnetic resonance imaging (MRI) of the brain (based on an epilepsy-specific brain MRI protocol) and cerebrospinal fluid (CSF) analysis. Tier III confidence level for the diagnosis of IE is based on the factors listed in tier I and II and identification of electroencephalographic abnormalities characteristic for seizure disorders. The authors recommend performing MRI of the brain and routine CSF analysis, after exclusion of reactive seizures, in dogs with age at epileptic seizure onset 6 years, inter-ictal neurological abnormalities consistent with intracranial neurolocalisation, status epilepticus or cluster seizure at epileptic seizure onset, or a previous presumptive diagnosis of IE and drug-resistance with a single antiepileptic drug titrated to the highest tolerable dose

Temperature-Dependent Ordering Phenomena of a Polyiodide System in a Redox-Active Ionic Liquid

Iodine added to iodide-based ionic liquids leads to dramatic changes of their physical properties which may have implications for technological applications. Here we study the phase diagram of 1-methyl 3-propylimidazolium iodide, the temperature versus iodine (I2) concentration. Above a threshold I2 concentration of 3.9 M, polyiodides are found to be the major determinant of the thermodynamic properties, where nucleation occurs at reduced temperatures leading to a crystalline phase followed by a nematic phase. At the highest concentrations and for increasing temperatures a phonon mode develops which gives indication of mesophases with both improved orientational order of the polyiodide chains and a degree of positional order close to melting. These novel results are important for the fundamental understanding of the physical properties in molten salts and for applications where ionic liquids are used as charge-transporting media such as in batteries and dye-sensitized solar cells

Behavior of a Metabolic Cycling Population at the Single Cell Level as Visualized by Fluorescent Gene Expression Reporters

BACKGROUND: During continuous growth in specific chemostat cultures, budding yeast undergo robust oscillations in oxygen consumption that are accompanied by highly periodic changes in transcript abundance of a majority of genes, in a phenomenon called the Yeast Metabolic Cycle (YMC). This study uses fluorescent reporters of genes specific to different YMC phases in order to visualize this phenomenon and understand the temporal regulation of gene expression at the level of individual cells within the cycling population. METHODOLOGY: Fluorescent gene expression reporters for different phases of the YMC were constructed and stably integrated into the yeast genome. Subsequently, these reporter-expressing yeast were used to visualize YMC dynamics at the individual cell level in cultures grown in a chemostat or in a microfluidics platform under varying glucose concentrations, using fluorescence microscopy and quantitative Western blots. CONCLUSIONS: The behavior of single cells within a metabolic cycling population was visualized using phase-specific fluorescent reporters. The reporters largely recapitulated genome-specified mRNA expression profiles. A significant fraction of the cell population appeared to exhibit basal expression of the reporters, supporting the hypothesis that there are at least two distinct subpopulations of cells within the cycling population. Although approximately half of the cycling population initiated cell division in each permissive window of the YMC, metabolic synchrony of the population was maintained. Using a microfluidics platform we observed that low glucose concentrations appear to be necessary for metabolic cycling. Lastly, we propose that there is a temporal window in the oxidative growth phase of the YMC where the cycling population segregates into at least two subpopulations, one which will enter the cell cycle and one which does not

Global Burden of Cardiovascular Diseases and Risk Factors, 1990-2019: Update From the GBD 2019 Study

Cardiovascular diseases (CVDs), principally ischemic heart disease (IHD) and stroke, are the leading cause of global mortality and a major contributor to disability. This paper reviews the magnitude of total CVD burden, including 13 underlying causes of cardiovascular death and 9 related risk factors, using estimates from the Global Burden of Disease (GBD) Study 2019. GBD, an ongoing multinational collaboration to provide comparable and consistent estimates of population health over time, used all available population-level data sources on incidence, prevalence, case fatality, mortality, and health risks to produce estimates for 204 countries and territories from 1990 to 2019. Prevalent cases of total CVD nearly doubled from 271 million (95% uncertainty interval [UI]: 257 to 285 million) in 1990 to 523 million (95% UI: 497 to 550 million) in 2019, and the number of CVD deaths steadily increased from 12.1 million (95% UI:11.4 to 12.6 million) in 1990, reaching 18.6 million (95% UI: 17.1 to 19.7 million) in 2019. The global trends for disability-adjusted life years (DALYs) and years of life lost also increased significantly, and years lived with disability doubled from 17.7 million (95% UI: 12.9 to 22.5 million) to 34.4 million (95% UI:24.9 to 43.6 million) over that period. The total number of DALYs due to IHD has risen steadily since 1990, reaching 182 million (95% UI: 170 to 194 million) DALYs, 9.14 million (95% UI: 8.40 to 9.74 million) deaths in the year 2019, and 197 million (95% UI: 178 to 220 million) prevalent cases of IHD in 2019. The total number of DALYs due to stroke has risen steadily since 1990, reaching 143 million (95% UI: 133 to 153 million) DALYs, 6.55 million (95% UI: 6.00 to 7.02 million) deaths in the year 2019, and 101 million (95% UI: 93.2 to 111 million) prevalent cases of stroke in 2019. Cardiovascular diseases remain the leading cause of disease burden in the world. CVD burden continues its decades-long rise for almost all countries outside high-income countries, and alarmingly, the age-standardized rate of CVD has begun to rise in some locations where it was previously declining in high-income countries. There is an urgent need to focus on implementing existing cost-effective policies and interventions if the world is to meet the targets for Sustainable Development Goal 3 and achieve a 30% reduction in premature mortality due to noncommunicable diseases

Associations between the 17q21 region and allergic rhinitis in 5 birth cohorts

Non peer reviewe

Racial and socioeconomic disparities in hip fracture care

BACKGROUND: Despite declines in both the incidence of and mortality following hip fracture, there are racial and socioeconomic disparities in treatment access and outcomes. We evaluated the presence and implications of disparities in delivery of care, hypothesizing that race and community socioeconomic characteristics would influence quality of care for patients with a hip fracture. METHODS: We collected data from the New York State Department of Health Statewide Planning and Research Cooperative System (SPARCS), which prospectively captures information on all discharges from nonfederal acute-care hospitals in New York State. Records for 197,290 New York State residents who underwent surgery for a hip fracture between 1998 and 2010 in New York State were identified from SPARCS using International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) codes. Multivariable regression models were used to evaluate the association of patient characteristics, social deprivation, and hospital/surgeon volume with time from admission to surgery, in-hospital complications, readmission, and 1-year mortality. RESULTS: After adjusting for patient and surgery characteristics, hospital/surgeon volume, social deprivation, and other variables, black patients were at greater risk for delayed surgery (odds ratio [OR] = 1.49; 95% confidence interval [CI] = 1.42, 1.57), a reoperation (hazard ratio [HR] = 1.21; CI = 1.11, 1.32), readmission (OR = 1.17; CI = 1.11, 1.22), and 1-year mortality (HR = 1.13; CI = 1.07, 1.21) than white patients. Subgroup analyses showed a greater risk for delayed surgery for black and Asian patients compared with white patients, regardless of social deprivation. Additionally, there was a greater risk for readmission for black patients compared with white patients, regardless of social deprivation. Compared with Medicare patients, Medicaid patients were at increased risk for delayed surgery (OR = 1.17; CI = 1.10, 1.24) whereas privately insured patients were at decreased risk for delayed surgery (OR = 0.77; CI = 0.74, 0.81), readmission (OR = 0.77; CI = 0.74, 0.81), complications (OR = 0.80; CI = 0.77, 0.84), and 1-year mortality (HR = 0.80; CI = 0.75, 0.85). CONCLUSIONS: There are race and insurance-based disparities in delivery of care for patients with hip fracture, some of which persist after adjusting for social deprivation. In addition to investigation into reasons contributing to disparities, targeted interventions should be developed to mitigate effects of disparities on patients at greatest risk. LEVEL OF EVIDENCE: Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence

Targeting Prostate Tumor Low-Molecular Weight Tyrosine Phosphatase for Oxidation-Sensitizing Therapy

Protein tyrosine phosphatases (PTPs) play major roles in cancer and are emerging as therapeutic targets. Recent reports suggest low-molecular weight PTP (LMPTP)-encoded by the ACP1 gene-is overexpressed in prostate tumors. We found ACP1 up-regulated in human prostate tumors and ACP1 expression inversely correlated with overall survival. Using CRISPR-Cas9-generated LMPTP knockout C4-2B and MyC-CaP cells, we identified LMPTP as a critical promoter of prostate cancer (PCa) growth and bone metastasis. Through metabolomics, we found that LMPTP promotes PCa cell glutathione synthesis by dephosphorylating glutathione synthetase on inhibitory Tyr270. PCa cells lacking LMPTP showed reduced glutathione, enhanced activation of eukaryotic initiation factor 2-mediated stress response, and enhanced reactive oxygen species after exposure to taxane drugs. LMPTP inhibition slowed primary and bone metastatic prostate tumor growth in mice. These findings reveal a role for LMPTP as a critical promoter of PCa growth and metastasis and validate LMPTP inhibition as a therapeutic strategy for treating PCa through sensitization to oxidative stress

Esophageal perforation in South of Sweden: Results of surgical treatment in 125 consecutive patients

<p>Abstract</p> <p>Background</p> <p>For many years there has been a debate as to which is the method of choice in treating patients with esophageal perforation. The literature consists mainly of small case series. Strategies for aiding patients struck with this disease is changing as new and less traumatic treatment options are developing. We studied a relatively large consecutive material of esophageal perforations in an effort to evaluate prognostic factors, diagnostic efforts and treatment strategy in these patients.</p> <p>Methods</p> <p>125 consecutive patients treated at the University Hospital of Lund from 1970 to 2006 were studied retrospectively. Prognostic factors were evaluated using the Cox proportional hazards model.</p> <p>Results</p> <p>Pre-operative ASA score was the only factor that significantly influenced outcome. Neck incision for cervical perforation (n = 8) and treatment with a covered stent with or without open drainage for a thoracic perforation (n = 6) had the lowest mortality. Esophageal resection (n = 8) had the highest mortality. A CAT scan or an oesophageal X-ray with oral contrast were the most efficient diagnostic tools. The preferred treatment strategy changed over the course of the study period, from a more aggressive surgical approach towards using covered stents to seal the perforation.</p> <p>Conclusion</p> <p>Pre-operative ASA score was the only factor that significantly influenced outcome in this study. Treatment strategies are changing as less traumatic options have become available. Sealing an esophageal perforation with a covered stent, in combination with open or closed drainage when necessary, is a promising treatment strategy.</p