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11.
From a pure motor disorder of the bowel, in the past few years, irritable bowel syndrome (IBS) has become a multifactorial disease that implies visceral hypersensitivity, alterations at the level of nervous and humoral communications between the enteric nervous system and the central nervous system, alteration of the gut microflora, an increased intestinal permeability and minimum intestinal inflammation. Psychological and social factors can interfere with the communication between the central and enteric nervous systems, and there is proof that they are involved in the onset of IBS and influence the response to treatment and outcome. There is evidence that abuse history and stressful life events are involved in the onset of functional gastrointestinal disorders. In order to explain clustering of IBS in families, genetic factors and social learning mechanisms have been proposed. The psychological features, such as anxiety, depression as well as the comorbid psychiatric disorders, health beliefs and coping of patients with IBS are discussed in relation to the symptoms and outcome. 相似文献
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Vidosava Rakocevic Stojanovic Stojan Peric Teodora Paunic Sanja Pavlovic Edita Cvitan Ivana Basta Marina Peric Milena Milicev Dragana Lavrnic 《Journal of clinical neuroscience》2013,20(7):1002-1006
The aim of this study was to analyze survival, causes of death and cardiologic predictors of sudden death in a large cohort of patients with myotonic dystrophy type 1 (DM1). The study was comprised of 171 adult DM1 patients hospitalized at the Neurology Clinic in a 20-year period. Severe electrocardiographic (ECG) abnormality included at least one of the following: rhythm other than sinus, PR interval of ?240 ms, QRS complex duration of 120 ms or more, and second-degree or third-degree atrioventricular (AV) block. Survival data were analyzed by the Kaplan–Meier test, log–rank test and Cox regression analysis. During the mean follow-up period of 9.4 ± 5.4 years, a pacemaker was implanted in 5.8% of DM1 patients and 14% of patients died. The mean age at death was 55.6 ± 12.5 years. The most common causes of death in our cohort were sudden death (41.7%) and respiratory failure (29.2%). The presence of palpitations (hazard ratio [HR] = 4.7, p < 0.05) and increased systolic blood pressure (HR = 9.8, p < 0.05) were significant predictors of sudden death. Among ECG parameters, severe ECG abnormality (HR = 4.7, p < 0.05), right bundle branch block (RBBB; HR = 3.9, p < 0.05) and bifascicular block (HR = 5.8, p < 0.05) were significant predictors of sudden death. 相似文献
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Anne Raben PhD Pia Siig Vestentoft PhD Jennie Brand-Miller PhD Elli Jalo MSc Mathjis Drummen PhD Liz Simpson PhD J. Alfredo Martinez PhD Teodora Handjieva-Darlenska PhD Gareth Stratton PhD Maija Huttunen-Lenz PhD Tony Lam MBA Jouko Sundvall MSc Roslyn Muirhead PhD Sally Poppitt PhD Christian Ritz PhD Kirsi H. Pietiläinen PhD Margriet Westerterp-Plantenga PhD Moira A. Taylor PhD Santiago Navas-Carretero PhD Svetoslav Handjiev PhD Melitta A. McNarry PhD Sylvia Hansen MSc Laura Råman BSc Shannon Brodie MSc Marta P. Silvestre PhD Tanja C. Adam PhD Ian A. Macdonald PhD Rodrigo San-Cristobal PhD Nadka Boyadjieva PhD Kelly A. Mackintosh PhD Wolfgang Schlicht PhD Amy Liu PhD Thomas M. Larsen PhD Mikael Fogelholm DSc 《Diabetes, obesity & metabolism》2021,23(2):324-337
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Promoter hypermethylation of CDKN2A,MGMT, MLH1, and DAPK genes in laryngeal squamous cell carcinoma and their associations with clinical profiles of the patients 下载免费PDF全文
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Hassan Awada Reda Z. Mahfouz Ashwin Kishtagari Teodora Kuzmanovic Jibran Durrani Cassandra M. Kerr Bhumika J. Patel Valeria Visconte Tomas Radivoyevitch Alan Lichtin Hetty E. Carraway Jaroslaw P. Maciejewski Yogen Saunthararajah 《British journal of haematology》2020,188(6):924-929
The nucleoside analogue decitabine can deplete the epigenetic regulator DNA methyltransferase 1 (DNMT1), an effect that occurs, and is saturated at, low concentrations/doses. A reason to pursue this molecular-targeted effect instead of the DNA damage/cytotoxicity produced with high concentrations/doses, is that non-cytotoxic DNMT1-depletion can cytoreduce even p53-null myeloid malignancies while sparing normal haematopoiesis. We thus identified minimum doses of decitabine (0·1–0·2 mg/kg) that deplete DNMT1 without off-target anti-metabolite effects/cytotoxicity, and then administered these well-tolerated doses frequently 1–2X/week to increase S-phase dependent DNMT1-depletion, and used a Myeloid Malignancy Registry to evaluate long-term outcomes in 69 patients treated this way. Consistent with the scientific rationale, treatment was well-tolerated and durable responses were produced (~40%) in genetically heterogeneous disease and the very elderly. 相似文献
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Vladan Milosevic Joanna Kopecka Iris C. Salaroglio Roberta Libener Francesca Napoli Stefania Izzo Sara Orecchia Preeta Ananthanarayanan Paolo Bironzo Federica Grosso Fabrizio Tabbò Valentina Comunanza Teodora Alexa-Stratulat Federico Bussolino Luisella Righi Silvia Novello Giorgio V. Scagliotti Chiara Riganti 《International journal of cancer. Journal international du cancer》2020,146(1):192-207
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Jelena Barbaric Giorgi Kuchukhidze Nicole Seguy Elena Vovc Maria Josefina Theresa Babovic Teodora Elvira Wi Daniel Low-Beer Ivana Bozicevic 《Euro surveillance : bulletin européen sur les maladies transmissibles = European communicable disease bulletin》2022,27(8)
BackgroundEpidemics of sexually transmitted infections (STI) are a major public health challenge in the World Health Organization (WHO) European Region.AimWe aimed to provide an overview of case reporting and other surveillance data for syphilis, gonorrhoea and chlamydia for the non-European Union (EU)/European Economic Area (EEA) countries of the Centre and East part of the WHO European Region as per classification used by the WHO Regional Office for Europe (WHO/Europe) and the European Centre for Disease Prevention and Control.MethodsData were provided by the surveillance agencies of the Member States for the period 2015 to 2019 through the WHO/Europe Communicable Diseases Annual Reporting Form. We analysed reported cases, explored data reported to the WHO Gonococcal Antimicrobial Surveillance Programme (GASP) and performed a review of publications on antimicrobial resistance (AMR) in gonorrhoea in the period 2015 to 2020 using systematic methodology.ResultsFrom 2015 to 2019, in most of the countries with three or more data points, there was a pattern of decrease in reported syphilis, gonorrhoea and chlamydia cases, which is in contrast to the EU/EEA. The number of reported cases per 100,000 population was 0.4–26.5 for syphilis, 0–18.5 for gonorrhoea and 0–43.3 for chlamydia. Four countries reported recent data on AMR in gonorrhoea to GASP, and we identified further publications from Georgia, Russia and Ukraine.ConclusionWe found wide heterogeneity in reported rates of STI. There is a strong need to improve availability and quality of STI surveillance data in the non-EU/EEA countries. 相似文献
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Roxana E. Iacob Teodora Pene-Dumitrescu Jianming Zhang Nathanael S. Gray Thomas E. Smithgall John R. Engen 《Proceedings of the National Academy of Sciences of the United States of America》2009,106(5):1386-1391
Protein dynamics are inextricably linked to protein function but there are few techniques that allow protein dynamics to be conveniently interrogated. For example, mutations and translocations give rise to aberrant proteins such as Bcr-Abl where changes in protein conformation and dynamics are believed to result in deregulated kinase activity that provides the oncogenic signal in chronic myelogeous leukemia. Although crystal structures of the down-regulated c-Abl kinase core have been reported, the conformational impact of mutations that render Abl resistant to small-molecule kinase inhibitors are largely unknown as is the allosteric interplay of the various regulatory elements of the protein. Hydrogen exchange mass spectrometry (HX MS) was used to compare the conformations of wild-type Abl with a nonmyristoylated form and with 3 clinically relevant imatinib resistance mutants (T315I, Y253H and E255V). A HX-resistant core localized to the interface between the SH2 and kinase domains, a region known to be important for maintaining the down-regulated state. Conformational differences upon demyristoylation were consistent with the SH2 domain moving to the top of the small lobe of the kinase domain as a function of activation. There were conformational changes in the T315I mutant but, surprisingly, no major changes in conformation were detected in either the Y253H or the E255V mutants. Taken together, these results provide evidence that allosteric interactions and conformational changes play a major role in Abl kinase regulation in solution. Similar analyses could be performed on any protein to provide mechanistic details about conformational changes and protein function. 相似文献