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https://www.readbyqxmd.com/read/28651363/multimodal-mechanistic-signatures-for-neurodegenerative-diseases-neurommsig-a-web-server-for-mechanism-enrichment
#1
Daniel Domingo-Fernández, Alpha Tom Kodamullil, Anandhi Iyappan, Mufassra Naz, Mohammad Asif Emon, Tamara Raschka, Reagon Karki, Stephan Springstubbe, Christian Ebeling, Martin Hofmann-Apitius
Motivation: The concept of a "mechanism-based taxonomy of human disease" is currently replacing the outdated paradigm of diseases classified by clinical appearance. We have tackled the paradigm of mechanism-based patient subgroup identification in the challenging area of research on neurodegenerative diseases. Results: We have developed a knowledge base representing essential pathophysiology mechanisms of neurodegenerative diseases. Together with dedicated algorithms, this knowledge base forms the basis for a "mechanism-enrichment server" that supports the mechanistic interpretation of multiscale, multimodal clinical data...
June 23, 2017: Bioinformatics
https://www.readbyqxmd.com/read/28650764/dorsal-fracture-dislocation-of-the-tarsal-navicularcase-report-and-review-of-a-rare-injury
#2
Isidro Jimenez, Juan Pedro Rodriguez-Alvarez, Ricardo Navarro-Navarro
Fracture-dislocations of the tarsal navicular are rare and highly complex injuries to the midfoot. The only published data on this type of fracture are clinical case reports. These injuries are normally caused by high-energy trauma, and their pathophysiology and most appropriate treatment remain unclear. We report a clinical case of a dorsal fracture-dislocation of the tarsal navicular bone associated with a medial swivel dislocation of the Chopart joint caused by a bicycle fall in a 20-year-old healthy man...
May 2017: Journal of the American Podiatric Medical Association
https://www.readbyqxmd.com/read/28650070/the-human-ventilatory-response-to-stress-rate-or-depth
#3
Michael J Tipton, Abbi Harper, Julian F R Paton, Joseph T Costello
Many stressors cause an increase in ventilation in humans. This is predominantly reported as an increase in minute ventilation (V̇E ). But, the same V̇E can be achieved by a wide variety of changes in the depth (tidal volume, VT ) and number of breaths (respiratory frequency, ƒR). This review investigates the impact of stressors including: cold, heat, hypoxia, pain and panic on the contributions of ƒR and VT to V̇E to see if they differ with different stressors. Where possible we also consider the potential mechanisms that underpin the responses identified, and propose mechanisms by which differences in ƒR and VT are mediated...
June 26, 2017: Journal of Physiology
https://www.readbyqxmd.com/read/28649490/frequency-dependent-changes-in-local-intrinsic-oscillations-in-chronic-primary-insomnia-a-study-of-the-amplitude-of-low-frequency-fluctuations-in-the-resting-state
#4
Fuqing Zhou, Suhua Huang, Ying Zhuang, Lei Gao, Honghan Gong
New neuroimaging techniques have led to significant advancements in our understanding of cerebral mechanisms of primary insomnia. However, the neuronal low-frequency oscillation remains largely uncharacterized in chronic primary insomnia (CPI). In this study, the amplitude of low-frequency fluctuation (ALFF), a data-driven method based on resting-state functional MRI, was used to examine local intrinsic activity in 27 patients with CPI and 27 age-, sex-, and education-matched healthy controls. We examined neural activity in two frequency bands, slow-4 (between 0...
2017: NeuroImage: Clinical
https://www.readbyqxmd.com/read/28649481/cardio-oncology-cancer-therapy-related-cardiovascular-complications-in-a-molecular-targeted-era-new-concepts-and-perspectives
#5
REVIEW
David Hurtado-de-Mendoza, Arturo Loaiza-Bonilla, Paula A Bonilla-Reyes, Gabriel Tinoco, Rodrigo Alcorta
Cardio-oncology is a medical discipline that identifies, prevents, and treats the cardiovascular complications related to cancer therapy. Due to the remarkable proliferation of new cancer therapies causing cardiovascular complications, such as hypertension, heart failure, vascular complications, and cardiac arrhythmia, we provide an extensive, comprehensive revision of the most up-to-date scientific information available on the cardiovascular complications associated with the use of newer, novel chemotherapeutic agents, including their reported incidence, suggested pathophysiology, clinical manifestations, potential treatment, and prevention...
May 18, 2017: Curēus
https://www.readbyqxmd.com/read/28649428/the-uk-me-cfs-biobank-for-biomedical-research-on-myalgic-encephalomyelitis-chronic-fatigue-syndrome-me-cfs-and-multiple-sclerosis
#6
Eliana M Lacerda, Erinna W Bowman, Jacqueline M Cliff, Caroline C Kingdon, Elizabeth C King, Ji-Sook Lee, Taane G Clark, Hazel M Dockrell, Eleanor M Riley, Hayley Curran, Luis Nacul
The UK ME/CFS Biobank was launched in August 2011 following extensive consultation with professionals and patient representatives. The bioresource aims to enhance research on myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), related to pathophysiology, biomarkers and therapeutic approaches. The cohort includes 18-60 year olds, encompassing 284 clinically-confirmed ME/CFS cases, 60 neurologist-diagnosed multiple sclerosis (MS) cases, and 135 healthy individuals. The Biobank contains blood samples, aliquoted into serum, plasma, peripheral blood mononuclear cells (PBMC), red blood cells/granulocyte pellet, whole blood, and RNA (totalling 29,863 aliquots)...
2017: Open J Bioresour
https://www.readbyqxmd.com/read/28649312/the-eu-aims-longitudinal-european-autism-project-leap-design-and-methodologies-to-identify-and-validate-stratification-biomarkers-for-autism-spectrum-disorders
#7
Eva Loth, Tony Charman, Luke Mason, Julian Tillmann, Emily J H Jones, Caroline Wooldridge, Jumana Ahmad, Bonnie Auyeung, Claudia Brogna, Sara Ambrosino, Tobias Banaschewski, Simon Baron-Cohen, Sarah Baumeister, Christian Beckmann, Michael Brammer, Daniel Brandeis, Sven Bölte, Thomas Bourgeron, Carsten Bours, Yvette de Bruijn, Bhismadev Chakrabarti, Daisy Crawley, Ineke Cornelissen, Flavio Dell' Acqua, Guillaume Dumas, Sarah Durston, Christine Ecker, Jessica Faulkner, Vincent Frouin, Pilar Garces, David Goyard, Hannah Hayward, Lindsay M Ham, Joerg Hipp, Rosemary J Holt, Mark H Johnson, Johan Isaksson, Prantik Kundu, Meng-Chuan Lai, Xavier Liogier D'ardhuy, Michael V Lombardo, David J Lythgoe, René Mandl, Andreas Meyer-Lindenberg, Carolin Moessnang, Nico Mueller, Laurence O'Dwyer, Marianne Oldehinkel, Bob Oranje, Gahan Pandina, Antonio M Persico, Amber N V Ruigrok, Barbara Ruggeri, Jessica Sabet, Roberto Sacco, Antonia San José Cáceres, Emily Simonoff, Roberto Toro, Heike Tost, Jack Waldman, Steve C R Williams, Marcel P Zwiers, Will Spooren, Declan G M Murphy, Jan K Buitelaar
BACKGROUND: The tremendous clinical and aetiological diversity among individuals with autism spectrum disorder (ASD) has been a major obstacle to the development of new treatments, as many may only be effective in particular subgroups. Precision medicine approaches aim to overcome this challenge by combining pathophysiologically based treatments with stratification biomarkers that predict which treatment may be most beneficial for particular individuals. However, so far, we have no single validated stratification biomarker for ASD...
2017: Molecular Autism
https://www.readbyqxmd.com/read/28649285/introduction-of-the-diagene-study-clinical-characteristics-pathophysiology-and-determinants-of-vascular-complications-of-type-2-diabetes
#8
Thijs T W van Herpt, Roosmarijn F H Lemmers, Mandy van Hoek, Janneke G Langendonk, Ronald J Erdtsieck, Bert Bravenboer, Annelies Lucas, Monique T Mulder, Harm R Haak, Aloysius G Lieverse, Eric J G Sijbrands
BACKGROUND: Type 2 diabetes is a major healthcare problem. Glucose-, lipid-, and blood pressure-lowering strategies decrease the risk of micro- and macrovascular complications. However, a substantial residual risk remains. To unravel the etiology of type 2 diabetes and its complications, large-scale, well-phenotyped studies with prospective follow-up are needed. This is the goal of the DiaGene study. In this manuscript, we describe the design and baseline characteristics of the study...
2017: Diabetology & Metabolic Syndrome
https://www.readbyqxmd.com/read/28648507/resistance-to-thyrotropin
#9
REVIEW
Helmut Grasberger, Samuel Refetoff
Resistance to thyrotropin (RTSH) is broadly defined as reduced sensitivity of thyroid follicle cells to stimulation by biologically active TSH due to genetic defects. Affected individuals have elevated serum TSH in the absence of goiter, with the severity ranging from nongoitrous isolated hyperthyrotropinemia to severe congenital hypothyroidism with thyroid hypoplasia. Conceptually, defects leading to RTSH impair both aspects of TSH-mediated action, namely thyroid hormone synthesis and gland growth. These include inactivating mutations in the genes encoding the TSH receptor and the PAX8 transcription factor...
March 2017: Best Practice & Research. Clinical Endocrinology & Metabolism
https://www.readbyqxmd.com/read/28648436/angiotensin-converting-enzyme-inhibitors-and-receptor-blockers-in-heart-failure-and-chronic-kidney-disease-demystifying-controversies
#10
REVIEW
Kader Muneer, Anishkumar Nair
In clinical setting, congestive heart failure (CHF) and chronic kidney disease (CKD) often co-exist in patients due to common underlying predisposing factors. An intricate equilibrium between the cardiovascular and renal system is maintained through rennin angiotensin-aldosterone axis and autonomic nervous system. Consequent to favorable hemodynamic modification, angiotensin converting enzyme inhibitors (ACEI) and angiotensin receptor blocking (ARB) therapy have proven to be an indispensable aspect of heart failure management with morbidity and mortality benefit...
May 2017: Indian Heart Journal
https://www.readbyqxmd.com/read/28648394/prevalence-correlates-and-prognostic-relevance-of-myocardial-mechanical-dispersion-as-assessed-by-feature-tracking-cardiac-magnetic-resonance-after-a-first-st-segment-elevation-myocardial-infarction
#11
Daniele Muser, Chiara Tioni, Ranjit Shah, Joseph B Selvanayagam, Gaetano Nucifora
Postinfarction mechanical dispersion (MD), that is, the regional heterogeneity of myocardial contraction throughout the cardiac cycle, has detrimental effects on left ventricular (LV) function and is related to the occurrence of heart failure and ventricular arrhythmias. However, its prevalence, pathophysiological determinants, and clinical utility are still unknown. The aim of the present study is to clarify these issues. In total, 130 consecutive patients (mean age 60 ± 12 years, 75% male) with a first ST-segment elevation myocardial infarction (STEMI) were included...
May 30, 2017: American Journal of Cardiology
https://www.readbyqxmd.com/read/28648120/long-qt-syndrome-associated-caveolin-3-mutations-differentially-regulate-the-hyperpolarization-activated-cyclic-nucleotide-gated-channel-4
#12
L J Motloch, R Larbig, T Darabi, S Reda, K A Motloch, B Wernly, M Lichtenauer, T Gebing, A Schwaiger, N Zagidullin, M Wolny, U C Hoppe
Background Caveolin-3 (cav-3) mutations are linked to the long-QT syndrome (LQTS) causing distinct clinical symptoms. Hyperpolarization-activated cyclic nucleotide channel 4 (HCN4) underlies the pacemaker current If. It associates with cav-3 and both form a macromolecular complex. Methods To examine the effects of human LQTS-associated cav-3 mutations on HCN4-channel function, HEK293-cells were cotransfected with HCN4 and wild-type (WT) cav-3 or a LQTS-associated cav-3 mutant (T78M, A85T, S141R, or F97C). HCN4 currents were recorded using the whole-cell patch-clamp technique...
June 26, 2017: Physiology International
https://www.readbyqxmd.com/read/28647708/relapsing-cerebral-amyloid-angiopathy-related-inflammation-the-wax-and-the-wane
#13
Sharfaraz Salam, Mayooreshan Anandarajah, Sarah Al-Bachari, Piyali Pal, Jonathan Sussman, Hisham Hamdalla
Cerebral amyloid angiopathy-related inflammation (CAA-I) is a rare variant of cerebral amyloid angiopathy (CAA). Its precise pathophysiology remains uncertain and we currently have limited evidence on which immunosuppressive agents are the most effective in its treatment. The disease course of CAA-I disorders can vary from an isolated clinical event to recurrent episodes. We present a case of biopsy-confirmed CAA-I that gives insight into its potential relapsing nature and the challenges of its long-term management...
June 24, 2017: Practical Neurology
https://www.readbyqxmd.com/read/28647569/sepsis-in-alcohol-related-liver-disease
#14
REVIEW
Thierry Gustot, Javier Fernandez, Gyongyi Szabo, Agustin Albillos, Alexandre Louvet, Rajiv Jalan, Richard Moreau, Christophe Moreno
Alcohol-related liver disease (ALD) remains the most important cause of death due to alcohol. Infections, particularly bacterial infections, are one of the most frequent and severe complications of advanced ALD, as alcoholic cirrhosis and severe alcoholic hepatitis (sAH). The specific mechanisms responsible of this altered host defence become to be deciphered. The aim of the present work is to review the current knowledge about infectious complications in ALD and the pathophysiological mechanisms, distinguishing the role of alcohol consumption and the contribution of different forms of ALD...
June 21, 2017: Journal of Hepatology
https://www.readbyqxmd.com/read/28647490/sex-biased-eicosanoid-biology-impact-for-sex-differences-in-inflammation-and-consequences-for-pharmacotherapy
#15
REVIEW
Simona Pace, Lidia Sautebin, Oliver Werz
The incidence, severity and progression of autoimmune diseases (e.g. scleroderma, multiple sclerosis, rheumatoid arthritis) and certain inflammatory diseases (e.g. asthma) are sex-biased where these pathologies dominate in women. However, other immune disorders such as sepsis, post-surgery infections and gout display higher incidence and severity in men. The molecular and cellular basis underlying this sex dimorphism remains incompletely elucidated but may provide important insights for sex-specific pharmacotherapy...
June 21, 2017: Biochemical Pharmacology
https://www.readbyqxmd.com/read/28647343/alcoholic-cardiomyopathy-what-is-known-and-what-is-not-known
#16
REVIEW
Antonio Mirijello, Claudia Tarli, Gabriele Angelo Vassallo, Luisa Sestito, Mariangela Antonelli, Cristina d'Angelo, Anna Ferrulli, Salvatore De Cosmo, Antonio Gasbarrini, Giovanni Addolorato
Excessive alcohol consumption represents one of the main causes of non-ischemic dilated cardiomyopathy. Alcoholic cardiomyopathy is characterized by dilation and impaired contraction of one or both myocardial ventricles. It represents the final effect of alcohol-induced toxicity to the heart. Several pathophysiological mechanisms have been proposed at the basis of alcohol-induced damage, most of which are still object of research. Unfortunately, symptoms of alcoholic cardiomyopathy are not specific and common to other forms of heart failure and appear when dilatation and systolic dysfunction are consolidated...
June 21, 2017: European Journal of Internal Medicine
https://www.readbyqxmd.com/read/28646803/effects-of-balneotherapy-on-serum-levels-of-shingosine-1-phosphate-in-patients-with-osteoarthritis
#17
Esra Aycan Ustyol, Fatih Karaarslan, Seldag Bekpinar, Kagan Ozkuk, Nergis Erdogan
Context • Balneotherapy is one of the most commonly used nonpharmacological interventions for osteoarthritis (OA), but its mechanism of action in relieving pain and stiffness and in improving physical function is not well understood. Studies have found that therapy provokes a series of neuroendocrinal reactions with anti-inflammatory and analgesic effects. Sphingosine-1-phosphate (S1P), a bioactive lipid, has been implicated as an important mediator in the maintenance of physiological processes (eg, vascular barrier integrity) and in pathophysiologic processes such as inflammatory conditions...
June 23, 2017: Alternative Therapies in Health and Medicine
https://www.readbyqxmd.com/read/28646532/acquired-bilateral-telangiectasia-macularis-eruptiva-perstans-a-unique-clinical-feature-of-photodamaging-rather-than-a-subtype-of-cutaneous-mastocytosis
#18
Hye-Rim Moon, Young Jae Kim, Joon Min Jung, Chong Hyun Won, Mi Woo Lee, Jee Ho Choi, Sung Eun Chang
Telangiectasia macularis eruptiva perstans (TMEP) is a rare subtype of cutaneous mastocytosis, characterized by telangiectatic tan to brown macules on the trunk and extremities. Although TMEP has been descried as an uncommon disease in the literature, we often encounter patients with TMEP lesions in the outpatient clinic. We aimed to assess the clinical and histopathological characteristics of acquired bilateral TMEP, and the pathophysiological mechanism of acquired bilateral TMEP among these patients. We retrospectively reviewed 30 patients (28 men and 2 women) with acquired bilateral TMEP; multiple telangiectatic dark red to brown macules that were symmetrically distributed...
June 23, 2017: Journal of Dermatology
https://www.readbyqxmd.com/read/28646358/metabolomics-of-diabetes-in-pregnancy
#19
REVIEW
Carolyn F McCabe, Wei Perng
PURPOSE OF REVIEW: The purpose of this review is to describe ways in which metabolomics may enhance understanding of gestational diabetes mellitus (GDM) etiology and refine current diagnostic criteria. RECENT FINDINGS: Current clinical recommendations suggest screening for GDM between 24 and 28 of gestational weeks using an oral glucose tolerance test. Despite this consensus, there are discrepancies regarding the exact criteria for GDM diagnosis. Further, emerging evidence has unveiled heterogeneous physiological pathways underlying GDM-specifically, GDM with defective insulin secretion vs...
August 2017: Current Diabetes Reports
https://www.readbyqxmd.com/read/28646120/mir-223-represents-a-biomarker-in-acute-and-chronic-liver-injury
#20
Florian Schueller, Sanchari Roy, Sven Heiko Loosen, Jan Alder, Christiane Koppe, Anne Theres Schneider, Franziska Wandrer, Heike Bantel, Mihael Vucur, Qing-Sheng Mi, Christian Trautwein, Tom Luedde, Christoph Roderburg
Background: Dysregulation of miRNAs has been described in tissue and serum from patients with acute and chronic liver diseases. However, only little information on the role of miR-223 in the pathophysiology of acute liver failure (ALF) and liver cirrhosis is available.  Methods: We analysed cell and tissue specific expression levels as well as serum concentrations of miR-223 in mouse models of acute (hepatic ischemia and reperfusion, single CCl4 injection) and chronic (repetitive CCl4 injection, bile duct ligation) liver diseases...
June 23, 2017: Clinical Science (1979-)
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