Publications by authors named "Konstantinos I Gourgoulianis"

215 Publications

In Silico investigation of the viroporin E as a vaccine target against SARS-CoV-2.

Am J Physiol Lung Cell Mol Physiol 2021 Apr 6. Epub 2021 Apr 6.

Department of Physiology, University Of Thessaly, Greece.

Viroporins, integral viral membrane ion channel proteins, interact with host-cell proteins deregulating physiological processes and activating inflammasomes. Severity of COVID-19 might be associated with hyperinflammation, thus we aimed at the complete immunoinformatic analysis of the SARS-CoV-2 viroporin E, P0DTC4. We also identified the human proteins interacting with P0DTC4 and the enriched molecular functions of the corresponding genes. The complete sequence of P0DTC4 in FASTA format was processed in 10 databases relative to secondary and tertiary protein structure analyses and prediction of optimal vaccine epitopes. Three more databases were accessed for the retrieval and the molecular functional characterization of the P0DTC4 human interactors. The immunoinformatics analysis resulted in the identification of 4 discontinuous B-cell epitopes along with 1 linear B-cell epitope and 11 T-cell epitopes which were found to be antigenic, immunogenic, non-allergen, non-toxin and unable to induce autoimmunity thus fulfilling prerequisites for vaccine design. The functional enrichment analysis showed that the predicted host interactors of P0DTC4 target the cellular acetylation network. Two of the identified host-cell proteins-BRD2 and BRD4- have been shown to be promising targets for anti-viral therapy. Thus, our findings have implications for COVID-19 therapy and indicate that viroporin E could serve as a promising vaccine target against SARS-CoV-2. Validation experiments are required to complement these in-silico results.
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http://dx.doi.org/10.1152/ajplung.00443.2020DOI Listing
April 2021

Outside-in induction of the IFITM3 trafficking system by infections, including SARS-CoV-2, in the pathobiology of Alzheimer's disease.

Brain Behav Immun Health 2021 Jul 26;14:100243. Epub 2021 Mar 26.

Department of Physiology, Faculty of Medicine, School of Health Sciences, University of Thessaly, BIOPOLIS, Larissa, 41500, Greece.

Background: IFITM3 is a viral restriction protein that enables sequestration of viral particles and subsequent trafficking to lysosomes. Recently, IFITM3 upregulation was found to induce gamma - secretase activity and the production of amyloid beta. The purpose of this study was to determine whether dysregulation of IFITM3-dependent pathways was present in neurons and peripheral immune cells donated by AD patients. As a secondary aim, we sought to determine whether these perturbations could be induced by viruses, including SARS-CoV-2.

Methods: Gene set enrichment analyses (GSEA) previously performed on publicly available transcriptomic data from tissues donated by AD patients were screened for enriched pathways containing IFITM3. Subsequently, signature containing IFITM3, derived from entorhinal cortex (EC) neurons containing neurofibrillary tangles (NFT) was screened for overlap with curated, publicly available, viral infection-induced gene signatures (including SARS-CoV-2).

Results: GSEA determined that IFITM3 gene networks are significantly enriched both in CNS sites (entorhinal and hippocampal cortices) and in peripheral blood mononuclear cells (PBMCs) donated by AD patients. Overlap screening revealed that IFITM3 signatures are induced by several viruses, including SARS-CoV, MERS-CoV, SARS-CoV-2 and HIV-1 (adjusted p-value <0.001; Enrichr Database).

Discussion: A data-driven analysis of AD tissues revealed IFITM3 gene signatures both in the CNS and in peripheral immune cells. GSEA revealed that an IFITM3 derived gene signature extracted from EC/NFT neurons overlapped with those extracted from publicly available viral infection datasets, including SARS-CoV-2. Our results are in line with currently emerging evidence on IFITM3's role in AD, and SARS-CoV-2's potential contribution in the setting of an expanded antimicrobial protection hypothesis.
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http://dx.doi.org/10.1016/j.bbih.2021.100243DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7997139PMC
July 2021

Alzheimer's Disease in Patients with Obstructive Sleep Apnea Syndrome.

Tanaffos 2020 Jul;19(3):176-185

Laboratory of Respiratory Sleep Disorders, Department of Respiratory Medicine, Faculty of Medicine University of Thessaly, Biopolis, Larissa, Greece.

Background: Obstructive sleep apnea syndrome (OSAS) is a disorder with high prevalence among adults and is an independent risk factor for various diseases, especially those affecting the central nervous system (CNS). Continuous positive airway pressure (CPAP) is usually the optimal choice of treatment for OSAS. Alzheimer's disease (AD) is a neurodegenerative disease affecting a large proportion of the elderly population. The purpose of this study was to collect information concerning the two pathological entities and investigate the effectiveness of CPAP in the treatment of AD.

Materials And Methods: In this review, Twenty articles were found concerning OSAS and AD, of which one article was about treatment with donepezil and seven articles considered treatment with CPAP.

Results: Serious OSAS and short sleep duration are associated with a high risk of developing dementia. Respiratory distress during sleep is associated with developing mild cognitive impairment at younger ages. The cerebrovascular damage of AD patients is correlated with the severity of OSAS. Lower cerebrospinal fluid levels are associated with memory disturbances and oxygen saturation parameters in patients with OSAS-AD. Continuous use of CPAP is related to the delayed onset of cognitive impairment and is suggested as an effective method of protecting cognitive function, depression, sleep quality and architecture, and daytime sleepiness in AD patients with good compliance. Treatment of CPAP patients with OSAS-AD is suggested as an effective method of protecting cognitive function.

Conclusion: Clinicians dealing with AD patients should consider CPAP treatment when OSAS coexists.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8008406PMC
July 2020

Temporal trends in pulmonary embolism prevalence in Greece during 2013-2017.

BMC Public Health 2021 Mar 21;21(1):559. Epub 2021 Mar 21.

Respiratory Medicine Department, University of Thessaly, School of Medicine, Biopolis (Mezourlo), 41110, Larissa, Greece.

Background: Pulmonary embolism (PE) epidemiological data about the disease prevalence in the general population are unclear. The present study aims to investigate the prevalence of PE in Greece and the associated temporal trends for the years 2013-2017.

Methods: Data on medical prescriptions for PE in the years 2013-2017 were provided by the Greek National Health Service Organization (EOPYY). Data on age, gender, specialty of the prescribing physician and prescription unit were provided as well.

Results: The total number of medical prescriptions for PE for the study period was 101,426. Of the total prescriptions, 51% were issued by the Public Sector and 48% by the Private Sector. In 2013 the prevalence of PE was 5.43 cases per 100,000 citizens and increased constantly until 2017 with 23.79 cases per 100,000 population. Prevalence was higher in all years studied in the age group of 70-80 years. For the year 2017, we observed 69.35 cases per 100,000 population for subjects 70-80 years, followed by the ages 80-90 (60.58/100,000) and 60-70 years (56.47 /100,000). Females displayed higher PE prevalence than males and higher increasing trend.

Conclusion: PE prevalence has an increasing trend throughout the years 2013-2017 while prevalence in females is higher than males and displays a higher increasing trend. Our results may be used to appropriately organize nationwide health care campaigns aiming at the diagnosis, treatment and prevention of PE.
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http://dx.doi.org/10.1186/s12889-021-10621-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7981863PMC
March 2021

Underestimation of respiratory symptoms by smokers: a thorn in chronic obstructive pulmonary disease diagnosis.

NPJ Prim Care Respir Med 2021 03 12;31(1):14. Epub 2021 Mar 12.

Department of Respiratory Medicine, Faculty of Medicine, University of Thessaly, BIOPOLIS, Larissa, Greece.

Primary care centers are ideal positions to identify chronic obstructive pulmonary disease (COPD). We determined the COPD prevalence among ever-smokers aged 40-65 years attending a 2-year program conducted in 22 Greek primary healthcare centers and made comparisons between genders, patients less than or greater than 55 years, and newly or previously diagnosed COPD patients. A total of 117 persons, after studying 1100 people, were diagnosed with previously unknown or known COPD, providing a COPD prevalence of 10.6% among the study population. In all, 7.5% of the participants were newly diagnosed with COPD. Women with COPD reported smoking less but experienced worse respiratory and depressive symptoms than men. A total of 19% of the COPD population below 55 years experienced wheezing and exacerbations more frequently than older patients. Newly diagnosed COPD patients were significantly younger, reported a significant burden of symptoms without seeking medical help. Primary health care has a crucial role in the early detection of COPD among unsuspecting smokers.
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http://dx.doi.org/10.1038/s41533-021-00226-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7955112PMC
March 2021

Acceptability of COVID-19 Vaccination among Greek Health Professionals.

Vaccines (Basel) 2021 Feb 28;9(3). Epub 2021 Feb 28.

Respiratory Medicine Department, Faculty of Medicine, University of Thessaly, 41500 Larissa, Greece.

Health Care Workers are at the front line of the fight against Covid-19. The aim of this study was to evaluate the acceptability of vaccination against COVID-19 among health professionals (physicians, dentists, pharmacists) two weeks prior to the start of the Greek vaccination campaign against COVID-19. A cross-sectional online survey was conducted over the period 15-22 December 2020 in 340 health professionals in Central Greece. We found a high level of acceptance for COVID-19 vaccine (78.5%) and a high vaccination coverage for the influenza vaccine (74%). Age > 45 years (OR = 2.01; 95% C.I. = 2.01-4.3), absence of fear over vaccine safety (OR = 4.09; 95% C.I. = 1.36-12.3), and information received from the Greek public health authorities (OR = 11.14; 95% C.I. = 5.48-22.6), were factors independently associated with the likelihood of COVID-19 vaccination acceptance. Our study indicates a high level of the COVID-19 vaccination acceptance among physicians, dentists and pharmacists. Nevertheless, several interventions can be implemented to increase acceptance of vaccine among health-care workers (HCWs) and could be especially directed at younger and vaccine-hesitant health care workers due to fear of vaccine side-effects. Last, our results provide some evidence that receiving vaccine-related information from the Greek Center for Diseases Control (E.O.D.Y.) could reduce the drivers of hesitancy and enhance the acceptability of COVID-19 vaccination.
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http://dx.doi.org/10.3390/vaccines9030200DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7997202PMC
February 2021

The role of nitric oxide in pleural disease.

Respir Med 2021 Apr 23;179:106350. Epub 2021 Feb 23.

Department of Physiology, Faculty of Medicine, University of Thessaly, BIOPOLIS, 41500, Larissa, Greece.

Nitric oxide (NO) regulates various physiological and pathophysiological functions in the lungs. However, there is much less information about the effects of NO in the pleura. The present review aimed to explore the available evidence regarding the role of NO in pleural disease. NO, has a double-edged role in the pleural cavity. It is an essential signaling molecule mediating various physiological cell functions such as lymphatic drainage of the serous cavities, the immune response to intracellular multiplication of pathogens, and downregulation of neutrophil migration, but also induces genocytotoxic and mutagenic effects when present in excess. NO is implicated in the pathogenesis of asbestos-related or exudative pleural disease and mesothelioma. From a clinical point of view, the fraction of exhaled NO has been suggested as a potential non-invasive tool for the diagnosis of benign asbestos-related disorders. Under experimental conditions, NO-mimetics were found to attenuate hypoxia-induced therapy resistance in mesothelioma. Similarly, hybrid agents consisting of an NO donor coupled with a parent anti-inflammatory drug showed an enhancement of the anti-inflammatory activity of anti-inflammatory drugs. However, given the paucity of research work performed over the last years in this area, further research should be undertaken to establish reliable conclusions with respect to the feasibility of determining or targeting the NO signaling pathway for pleural disease diagnosis and therapeutic management.
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http://dx.doi.org/10.1016/j.rmed.2021.106350DOI Listing
April 2021

HΜGB1/sRAGE levels differ significantly between transudates and exudates.

Cytokine 2021 May 16;141:155469. Epub 2021 Feb 16.

Department of Respiratory Medicine, Faculty of Medicine, University of Thessaly, BIOPOLIS, 41500 Larissa, Greece; Department of Physiology, Faculty of Medicine, University of Thessaly, BIOPOLIS, 41500 Larissa, Greece. Electronic address:

High mobility group box 1(HMGB1) protein operates as an alarmin with multiple roles in immunity and cell homeostasis. It is highly expressed in epithelial barrier sites and acts via the binding to the receptor for advanced glycation end products (RAGE). Production of HMGB1 and soluble RAGE (sRAGE), a decoy receptor for HMGB1, has been implicated in several pulmonary diseases, but both have been scarcely investigated in pleural diseases. The aim of this study was to determine the levels of HMGB1 and sRAGE in transudative, malignant and parapneumonic pleural effusions (PEs) and to investigate the effect of low and high HMGB1 pleural fluid levels on MeT-5A cell adhesion, migration and spheroid formation, in each group. HMGB1 and sRAGE levels were significantly lower and higher in transudative PEs compared to malignant and parapneumonic PEs, respectively. Patients above 65 years of age had significantly lower HMGB1 and higher sRAGE levels compared to patients below 65 years old. Furthermore, incubation of MeT-5A cells with malignant or parapneumonic PEs bearing low or high levels of HMGB1 yielded significant differential effects on MeT-5A cell adhesion, migration and spheroid formation. In all types of effusions, high HMGB1 levels correlated with more adherence compared to low HMGB1 levels. In transudative and malignant PEs high HMGB1 levels correlated with decreased migration of MeT-5A cells while in parapneumonic ones the effect was the opposite. Only samples from parapneumonic PEs high in HMGB1 achieved uniform spheroid formation. These results reveal a clinical context-dependent effect of the HMGB1/sRAGE axis in PEs.
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http://dx.doi.org/10.1016/j.cyto.2021.155469DOI Listing
May 2021

Repeated Antigen-Based Rapid Diagnostic Testing for Estimating the Coronavirus Disease 2019 Prevalence from the Perspective of the Workers' Vulnerability before and during the Lockdown.

Int J Environ Res Public Health 2021 02 9;18(4). Epub 2021 Feb 9.

Department of Respiratory Medicine, Faculty of Medicine, University of Thessaly, BIOPOLIS, 41110 Larissa, Greece.

Background: No previous study has investigated the SARS-CoV-2 prevalence and the changes in the proportion of positive results due to lockdown measures from the angle of workers' vulnerability to coronavirus in Greece. Two community-based programs were implemented to evaluate the SARS-CoV-2 prevalence and investigate if the prevalence changes were significant across various occupations before and one month after lockdown.

Methods: Following consent, sociodemographic, clinical, and job-related information were recorded. The VivaDiag™ SARS-CoV-2 Antigen Rapid Test was used. Positive results confirmed by a real-time Reverse Transcriptase Polymerase Chain Reaction for SARS-COV-2.

Results: Positive participants were more likely to work in the catering/food sector than negative participants before the lockdown. Lockdown restrictions halved the new cases. No significant differences in the likelihood of being SARS-CoV-2 positive for different job categories were detected during lockdown. The presence of respiratory symptoms was an independent predictor for rapid antigen test positivity; however, one-third of newly diagnosed patients were asymptomatic at both time points.

Conclusions: The catering/food sector was the most vulnerable to COVID-19 at the pre-lockdown evaluation. We highlight the crucial role of community-based screening with rapid antigen testing to evaluate the potential modes of community transmission and the impact of infection control strategies.
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http://dx.doi.org/10.3390/ijerph18041638DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7915907PMC
February 2021

Calprotectin in Lung Diseases.

Int J Mol Sci 2021 Feb 8;22(4). Epub 2021 Feb 8.

Department of Respiratory Medicine, Faculty of Medicine, University of Thessaly, 41110 Larissa, Greece.

Calprotectin (CLP) is a heterodimer formed by two S-100 calcium-binding cytosolic proteins, S100A8 and S100A9. It is a multifunctional protein expressed mainly by neutrophils and released extracellularly by activated or damaged cells mediating a broad range of physiological and pathological responses. It has been more than 20 years since the implication of S100A8/A9 in the inflammatory process was shown; however, the evaluation of its role in the pathogenesis of respiratory diseases or its usefulness as a biomarker for the appropriate diagnosis and prognosis of lung diseases have only gained attention in recent years. This review aimed to provide current knowledge regarding the potential role of CLP in the pathophysiology of lung diseases and describe how this knowledge is, up until now, translated into daily clinical practice. CLP is involved in numerous cellular processes in lung health and disease. In addition to its anti-microbial functions, CLP also serves as a molecule with pro- and anti-tumor properties related to cell survival and growth, angiogenesis, DNA damage response, and the remodeling of the extracellular matrix. The findings of this review potentially introduce CLP in daily clinical practice within the spectrum of respiratory diseases.
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http://dx.doi.org/10.3390/ijms22041706DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7915440PMC
February 2021

Cell and extracellular matrix interaction models in benign mesothelial and malignant pleural mesothelioma cells in 2D and 3D in-vitro.

Clin Exp Pharmacol Physiol 2021 Apr 17;48(4):543-552. Epub 2020 Dec 17.

Department of Physiology, Faculty of Medicine, University of Thessaly, BIOPOLIS, Larissa, Greece.

Malignant pleural mesothelioma (MPM) is an aggressive tumour that grows in the pleural cavity. MPM spheroids released in the pleural fluid can form new tumour foci. Cell-cell, cell-extracellular matrix (ECM) interactions in 2D and 3D impact malignant cell behaviour during cell adhesion, migration, proliferation and epithelial-mesenchymal transition (EMT). In this study, epithelioid, biphasic and sarcomatoid MPM cell types as well as benign mesothelial cells were tested with regards to the above phenotypes. Fibronectin (FN) and homologous cell-derived extracellular matrix (hcd-ECM) treated substratum differentially affected the above phenotypes. 3D MPM spheroid invasion was higher in FN-collagen matrices in the epithelioid and biphasic cells, while 3D cell cultures of epithelioid and sarcomatoid MPM cells in FN-collagen showed a higher contractility compared to hcd-ECM-collagen. Cell aggregates demonstrated invasive behaviour in hcd-ECM matrices alone. Our results suggest that ECM and the dimensionality affect malignant cell behaviour during cell culture studies.
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http://dx.doi.org/10.1111/1440-1681.13446DOI Listing
April 2021

Pleural effusion osmolality correlation with pH and glucose level of pleural fluid and its effects on the pleural membrane permeability.

Respir Physiol Neurobiol 2021 Mar 12;285:103581. Epub 2020 Nov 12.

Department of Physiology, Faculty of Medicine, University of Thessaly, BIOPOLIS, 41500, Larissa, Greece; Department of Respiratory Medicine, Faculty of Medicine, University of Thessaly, BIOPOLIS, 41500, Larissa, Greece. Electronic address:

Background And Aim: Pleural effusions (PE) are a common clinical entity resulting from pathologies that affect the pleural space such as congestive heart failure, malignancy and pneumonia. The osmolality of the pleural fluid has never been studied as well as the effects of its changes on the pleural membrane. The purpose of this study was to identify the osmolality levels of PEs of different etiologies and to assess the potential effects of osmolality imbalance on the pleural permeability.

Materials And Methods: We measured the osmolality of the PEs of 64 consecutive patients (6 with transudative, 11 with parapneumonic and 47 with malignant pleural effusions) that were hospitalized in the University Hospital of Larissa. Subsequently, we selected clinically relevant hyper- and hypo- osmolality levels and performed assessment of the permeability of sheep parietal pleura by means of Ussing chamber experiments.

Results: The mean pleural fluid osmolality was 291.7 ± 24.89 mOms/Kg (95 % CI: 285.4-297.9), and it varied among the three groups of PEs (p = 0.05). Transformed osmolality values were associated with pH and glucose levels in the PEs. After exposure of the sheep parietal pleura to 240 mOsm/kg (hyposmolar) the transmesothelial resistance (R) significantly increased (p < 0.05) while at 340 mOsm/kg (hyperosmolar) the R was not significantly altered.

Conclusions: PEs osmolality differs depending on the underlying pathology and is linked to PE pH and glucose. Hypo-osmotic PEs can lead to decreased pleural permeability. These results warrant further study of the PEs osmolality levels on the function of the pleural mesothelial cells.
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http://dx.doi.org/10.1016/j.resp.2020.103581DOI Listing
March 2021

Fighting with the Lernean Hydra: Greek Humanitarian Crisis Enters Worst-Case Scenario. Comment on: Joseph, L.; Ismail, S.A.; Gunst, M.; Jarman, K.; Prior, D.; Harris, M.; Abbara, A. A Qualitative Research Study Which Explores Humanitarian Stakeholders' Views on Healthcare Access for Refugees in Greece. 2020, , 6972.

Int J Environ Res Public Health 2020 11 9;17(21). Epub 2020 Nov 9.

Metsovion Interdisciplinary Research Center, National Technical University of Athens, 44200 Athens, Greece.

Liz Joseph and collaborators shed light upon the real challenges of securing health during the Greek humanitarian crisis from the point of view of the key stakeholders in healthcare access, reflecting the need to reform a range of different contexts and types of humanitarian response [...].
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http://dx.doi.org/10.3390/ijerph17218253DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7664909PMC
November 2020

Burnout and associated factors among Greek substance use disorder treatment providers during economic crisis.

Arch Environ Occup Health 2020 Nov 5:1-7. Epub 2020 Nov 5.

Saint Elizabeth's Hospital and George Washington University School of Medicine, Washington, DC, USA.

Crisis and austerity in Greece could have influenced the risk of burnout among substance use disorder treatment providers. We aimed to investigate the prevalence of burnout and its associated factors among Greek substance use disorder treatment providers during economic crisis. A cross-sectional study was conducted in 2016. In particular, employees at the substance use treatment program of Athens ( = 180), a branch of the Greek Organization against Drugs were invited to participate. Almost all participants reported medical supplies shortages related to the economic crisis. Increasing job demands, staff reduction and limited job autonomy were independent risk factors for burnout. These factors are crisis-related. In conclusion, we found high rates of burnout among substance abuse treatment personnel in Greece. These respondents are a bellwether of the effects of economic crisis. Economic crisis can produce a profound negative effect on health care.
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http://dx.doi.org/10.1080/19338244.2020.1842311DOI Listing
November 2020

The Use of a Novel Quantitative Marker of Echogenicity of Pleural Fluid in Parapneumonic Pleural Effusions.

Can Respir J 2020 5;2020:1283590. Epub 2020 Oct 5.

Respiratory Medicine Department, University of Thessaly, School of Medicine, Larissa, Greece.

Background: Thoracic ultrasound is an essential tool in the daily clinical care of pleural effusions and especially parapneumonic pleural effusions (PPEs), in terms of diagnosis, management, and follow-up. Hypoechogenicity index (HI) is a quantitative marker of pleural fluid echogenicity. We aimed to examine associations of HI with pleural inflammation in patients with PPE.

Methods: All patients included underwent a thoracic ultrasound with HI determination at the first day of their admission for a PPE. Thoracentesis was performed in all patients. Demographics, laboratory measurements, and clinical data were collected prospectively and recorded in all subjects.

Results: Twenty-four patients with PPE were included in the study. HI was statistically significantly correlated with intensity of inflammation as suggested by pleural fluid LDH ( < 0.001,  = -0.831), pleural fluid glucose (=0.022,  = 0.474), and pleural fluid pH ( < 0.001,  = 0.811). HI was correlated with ADA levels (=0.005,  = -0.552). We observed a statistically significant correlation of HI with pleural fluid total cell number ( < 0.001,  = -0.657) and polymorphonuclears percentage (=0.02,  = -0.590), as well as days to afebrile (=0.046,  = -0.411), duration of chest tube placement ( < 0.001,  = -0.806), and days of hospitalization (=0.013,  = -0.501). . HI presents a fast, easily applicable, objective, and quantitative marker of pleural inflammation that reliably reflects the intensity of pleural inflammation and could potentially guide therapeutic management of PPE.
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http://dx.doi.org/10.1155/2020/1283590DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7556052PMC
October 2020

Double hit viral parasitism, polymicrobial CNS residency and perturbed proteostasis in Alzheimer's disease: A data driven, in silico analysis of gene expression data.

Mol Immunol 2020 11 21;127:124-135. Epub 2020 Sep 21.

Department of Neurology, Athens Naval Hospital, P.C. 115 21, Athens, Greece.

The aim of this study was to determine the interaction of peripheral immunity vs. the CNS in the setting of AD pathogenesis at the transcriptomic level in a data driven manner. For this purpose, publicly available gene expression data from the GEO Datasets repository. We performed differential gene expression and functional enrichment analyses were performed on the five retrieved studies: (a) three hippocampal cortex (HC) studies (b) one study of peripheral blood mononuclear cells (PBMC) and (c) one involving neurofibrillary tangle - containing neurons of the entorhinal cortex (NFT EC). Subsequently, BLAST was used to determine protein conservation between human proteins vs. microbial, whereas putative protein / oligopeptide antigenicity were determined via RANKPep. Gene ontology and pathway analyses revealed significantly enriched viral parasitism pathways in both PBMC and NFT - EC datasets, mediated by ribosomal protein families and epigenetic regulators. Among these, a salient viral pathway referred to Influenza A infection. NFT - EC annotations included leukocyte chemotaxis and immune response pathways. All datasets were significantly enriched for infectious pathways, as well as pathways involved in impaired proteostasis and non - phagocytic cell phagosomal cascades. In conclusion, our in silico analysis outlined an ad hoc model of AD pathophysiology in which double hit (PBMC and NFT-EC) viral parasitism is mediated by eukaryotic translational hijacking, and may be further implicated by impaired immune responses. Overall, our results overlap with the antimicrobial protection hypothesis of AD pathogenesis and support the notion of a pathogen - driven etiology.
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http://dx.doi.org/10.1016/j.molimm.2020.08.021DOI Listing
November 2020

Physical Activity and Quality of Sleep in Patients with End-Stage Renal Disease on Hemodialysis: A Preliminary Report.

Sleep Disord 2020 26;2020:6918216. Epub 2020 Aug 26.

Laboratory of Cardio-Pulmonary Testing and Pulmonary Rehabilitation, Department of Respiratory Medicine, Faculty of Medicine, University of Thessaly, Larissa, Greece.

Chronic kidney disease significantly impairs patients' daily lives and worsens their quality of life. The aim of this study was to investigate the physical activity and quality of sleep, during three days (previous day of dialysis, on the day of dialysis and after day of dialysis), in patients with end-stage renal on hemodialysis. 12 hemodialysis patients were included in our study, answered the Pittsburgh Sleep Quality Index (PSQI) questionnaire, and for each patient were used a smart bracelet for three days (day-pre- and posthemodialysis and day at hemodialysis) to record daily physical activity (steps, distance) and estimate the quality of sleep. Results showed differences between three days average of steps and distance and PSQI parameters "…engaging in social activity?" (steps, = 0.006, distance, = 0.006) and "…enthusiasm to get things done?" (steps, = 0.029, distance, = 0.030). Our study suggests interrelationship between sleep quality and physical activity.
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http://dx.doi.org/10.1155/2020/6918216DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7471812PMC
August 2020

Letter to Editor regarding Prata et al. (2020), Temperature significantly changes COVID-19 transmission in (sub)tropical cities of Brazil. Science of Total Environment, v729, 138862.

Sci Total Environ 2020 12 28;746:141323. Epub 2020 Jul 28.

Respiratory Medicine Department, Faculty of Medicine, University of Thessaly, BIOPOLIS, 41110 Larissa, Thessaly, Greece.

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http://dx.doi.org/10.1016/j.scitotenv.2020.141323DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7385549PMC
December 2020

Epigenetic regulation of apoptosis via the PARK7 interactome in peripheral blood mononuclear cells donated by tuberculosis patients vs. healthy controls and the response to treatment: A systems biology approach.

Tuberculosis (Edinb) 2020 07 31;123:101938. Epub 2020 May 31.

Department of Respiratory Medicine, Faculty of Medicine, University of Thessaly, BIOPOLIS, Mezourlo, 41110, Larisa, Greece.

Aims: The aims of our study were to determine for the first time differentially expressed genes (DEGs) and enriched molecular pathways involving the PARK7 interactome in PBMCs donated from tuberculosis patients.

Methods: Data on a previously reconstructed PARK7 interactome (Vavougios et al., 2017) from datasets GDS4966 (Case-Control) and GDS4781 (Treatment Series) were retrieved from the Gene Expression Omnibus (GEO) repository. Gene Enrichment analysis was performed via the STRING algorithm and the GeneTrail2 software.

Results: 17 and 22 PARK7 interactores were determined as DEGs in the active TB vs HD and Treatment Series subset analyses, correspondingly, associated with significantly enriched pathways (FDR <0.05) involving p53 and PTEN mediated, stress responsive apoptosis regulation pathways. The treatment subset was characterized by the emergence of an additional layer of transcriptional regulation mediated by polycomb proteins among others, as well as TLR-mediated and cytokine survival signaling. Finally, the enrichment of a Parkinson's disease signature including PARK7 interactors was determined by its differential regulation both in the exploratory analyses (FDR = 0.024), as well as the confirmatory analyses (FDR = 1.81e).

Conclusions: Our in silico analysis revealed for the first time the role of PARK7's interactome in regulating the epigenetics of the PBMC lifecycle and Mtb symbiosis.
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http://dx.doi.org/10.1016/j.tube.2020.101938DOI Listing
July 2020

Serum vitamin D levels in patients with obstructive sleep apnea syndrome and level changes after continuous positive airway pressure therapy.

Sleep Breath 2020 Aug 1. Epub 2020 Aug 1.

Laboratory of Respiratory Sleep Disorders, Department of Respiratory Medicine, Faculty of Medicine, University of Thessaly, Larissa, Greece.

Purpose: Patients with obstructive sleep apnea syndrome (OSAS) have been found to exhibit lower serum vitamin D levels, even when the control groups are matched for confounding conditions. However, contradictory studies are also present. This study aimed to compare serum 25-hydroxyvitamin D (25(OH)D) levels between adult patients with OSAS and non-apneic controls and to evaluate the changes in 25(OH)D levels after 3 and 12 months of continuous positive airway pressure (CPAP) therapy.

Methods: The study was comprised of 30 patients with OSAS and 30 controls. Serum 25(OH)D levels were determined at baseline and after 3 and 12 months of CPAP therapy in all patients with OSAS. For analysis, patients with OSAS were divided into subgroups by adherence, with adherence defined as CPAP usage for > 4 h per night on at least 70% of nights.

Results: The 25(OH)D levels were not significantly different between OSAS and control groups at baseline. 25(OH)D levels did not change after 3 and 12 months of CPAP therapy. Patients who were CPAP-adherent showed less reduction in 25(OH)D levels compared with non-adherent ones (21.18 ± 9.3 vs. 12.13 ± 3.8 ng/mL, p = 0.022) after 1 year. The 25(OH)D levels were significantly correlated with higher daily CPAP usage at 3 and 12 months. Mean daily CPAP usage was a significant predictor of serum 25(OH)D levels at 12 months.

Conclusions: Patients with OSAS who demonstrated good CPAP adherence showed significantly higher 25(OH)D levels after 1 year compared with those not adequately using CPAP. Long-term good CPAP adherence and highly daily CPAP usage positively affected 25(OH)D levels in patients with OSAS.
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http://dx.doi.org/10.1007/s11325-020-02146-6DOI Listing
August 2020

25-hydroxyvitamin D levels in patients with obstructive sleep apnea and continuous positive airway pressure treatment: a brief review.

Sleep Sci 2020 Jan-Mar;13(1):78-83

Laboratory of Respiratory Sleep Disorders, Department of Respiratory Medicine, Faculty of Medicine University of Thessaly, Larissa, Greece.

The aim of the present study is to summarize the information available, to time, regarding the relationship between obstructive sleep apnea (OSA) and vitamin-D (vD) levels. Moreover, the association between vD deficiency and OSA severity will also be examined. At the end of the present study the possible advantageous effect of CPAP on vD-levels will be summarized. Extensive literature search was conducted in PubMed, Scopus, The Cochrane Library and Embase database. 13 articles were found concerning OSA and vD, of which 2 articles included treatment with a CPAP. Patients with OSA exhibit low levels of vD in the blood serum, and women present an even lower mean value than men. Lack of VD in blood serum seems to be related to the severity of the OSA syndrome, and to the short duration of sleep. OSA patients with concurrent metabolic syndrome exhibit lower serum vD-levels, as compared with those without metabolic syndrome. Long-term continuous positive airway pressure treatment (CPAP) treatment can increase vD-levels in male OSA patients while no change is observed in women. OSA patients demonstrate lower levels of vD in multiple studies. The severity of the OSA may be associated with vD-levels and deficiency, however more studies are needed to assess that relationship due to contradictions in current bibliography. CPAP can increase vD-levels in male patients. The relation between vD and OSA and/or CPAP is important but recent; therefore further research is needed about the exact relationship to be clarified. Also, the effect of gender hormones on vD regulation in OSA patients should be further investigated.
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http://dx.doi.org/10.5935/1984-0063.20190126DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7347362PMC
July 2020

Vaccination Coverage of the Elderly in Greece: A Cross-Sectional Nationwide Study.

Can J Infect Dis Med Microbiol 2020 27;2020:5459793. Epub 2020 Jun 27.

Department of Respiratory Medicine, School of Health Sciences, Medical Faculty, University of Thessaly, Larissa, Greece.

Vaccines are important for older adults, and the morbidity and mortality of vaccine-preventable diseases among older adults are high. There are limited data on vaccination coverage among elderly people in Greece. The aim of this observational study was to record the vaccination coverage for vaccines recommended by the National Vaccination Program in Greece for the elderly people ≥60 years old. Two hundred general practitioners (GPs) around the country from the primary healthcare system were invited to "participate," and one hundred fifty from them participated in the present study. The GPs were selected using geographically stratified random sampling methodology. Two thousand and seventy-two participants participated in the present study: of which, 1043 were males and 1029 were females. The mean age of the participants was 73.3 years, and 83% vaccination coverage for flu vaccine, 49.5% for conjugate pneumococcal vaccine, and 23.5% for polysaccharide pneumococcal vaccine were recorded. In addition, the vaccination coverage for herpes zoster vaccine was 20%, while very low percentages were recorded for diphtheria, tetanus, pertussis, and polio vaccine for adults. We found significant gaps in vaccination coverage, especially with regard to pneumococcal, herpes zoster, and tetanus. On the contrary, influenza vaccination coverage was satisfactory.
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http://dx.doi.org/10.1155/2020/5459793DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7338982PMC
June 2020

Chronic Progressive Dyspnea in a 71-Year-Old Man: A Diagnostic Ithaca After 8 Years of Consultation.

Chest 2020 Jul 2;158(1):e25-e31. Epub 2020 Jul 2.

Department of Respiratory Medicine, Faculty of Medicine, University of Thessaly, Biopolis, Larissa, Greece.

Case Presentation: A 71-year-old ex-bus driver (ex-smoker, 20 pack-years) was admitted for the first time to the respiratory department because of chronic dry cough and progressive exertional dyspnea with insidious onset 8 years ago. The patient also reported weight loss of about 20 kg in 3 years and proximal muscle weakness. A decade ago, he was diagnosed with gastric adenocarcinoma and subjected to partial gastrectomy and splenectomy, followed by an unspecified chemotherapy regimen. Additionally, the patient has coronary disease and underwent coronary bypass graft surgery 7 years ago. In the course of his disease, many diagnostic procedures have been performed including Mantoux tests, five CT scans, a CT-guided biopsy, two bronchoscopies, and an 18F-fluorodeoxyglucose PET scan with inconclusive results. The patient was referred to the hospital to have his long-lasting condition diagnosed and treated.
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http://dx.doi.org/10.1016/j.chest.2020.02.003DOI Listing
July 2020

Assessment of Knowledge, Attitudes, and Practices towards New Coronavirus (SARS-CoV-2) of Health Care Professionals in Greece before the Outbreak Period.

Int J Environ Res Public Health 2020 07 8;17(14). Epub 2020 Jul 8.

Respiratory Medicine Department, Faculty of Medicine, University of Thessaly, 41100 Larissa, Greece.

Introduction: The ongoing severe acute respiratory syndrome (SARS)-CoV-2 pandemic has expanded globally. The aim of the current study is to investigate the knowledge, attitudes, and practices (KAP) of health care professionals in Greece towards SARS-CoV-2.

Methods: From 10-25 February 2020, 500 health care workers were approached. Knowledge, attitudes, and practices towards SARS-CoV-2 were assessed via a personal interview questionnaire. For knowledge, each correct answer was given 1 point; attitudes, or concerns aimed at prevention of SARS-CoV-2 infection, and practices, or behaviors towards performing preventive practices, were assigned 1 point each. Points were summed and a score for each category was calculated.

Results: A total of 461 health care workers returned the questionnaire and were included in the analysis (mean age ± SD: 44.2 ± 10.78 years, 74% females). The majority were nurses (47.5%), followed by physicians (30.5%) and paramedics (19%). The majority of subjects (88.28%) had a good level of knowledge (knowledge score equal to 4, or more). The majority of participants (71%) agreed with the temporary traveling restrictions ban. The uptake of a future vaccine against SARS-CoV-2 was estimated at 43%. Knowledge score was significantly associated with both attitudes score ( = 0.011) and practices score ( < 0.001), indicating that subjects with a high knowledge score demonstrated a more positive perception on preventive measures and would practice more preventive measures. Attitudes score was significantly associated with practices score ( = 0.009) indicating that subjects with a higher attitudes score are more likely to perform practices towards the prevention of SARS-CoV-2 transmission.

Conclusion: There is a high level of knowledge concerning SARS-CoV-2 pandemic among Greek health care workers and this is significantly associated with positive attitudes and practices towards preventive health measures. The high level of knowledge of health professionals about SARS-CoV-2 may have contributed considerably to the successful management of the pandemic in Greece. Tailored educational campaigns aiming to increase the proportion of health care workers willing to accept a potential SARS-CoV-2 vaccine could be of paramount importance in future proactive vaccine educational campaigns.
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http://dx.doi.org/10.3390/ijerph17144925DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7400230PMC
July 2020

The Reciprocal Association between Fitness Indicators and Sleep Quality in the Context of Recent Sport Injury.

Int J Environ Res Public Health 2020 07 3;17(13). Epub 2020 Jul 3.

The Medical Project, Prevention, Evaluation and Recovery Center, 41335 Larissa, Greece.

The purpose of the study is to investigate whether the oxygen uptake and heart rate at rest, in Greek professional soccer players, are affected by recent injuries, as well as how sleep quality is affected. Forty-two male professional soccer players were included in the study and divided into two groups: injury (n = 22, age: 21.6 ± 5.4 years, body fat: 11.0 ± 3.9%, total body water: 64.0 ± 2.5%) and no-injury (n = 20, age: 24.2 ± 5.6 years, body fat: 10.1 ± 2.8%, total body water: 64.3 ± 1.8%). The oxygen uptake at rest (O, mL/min/kg) and heart rate (HR, bpm) were recorded in the upright position for 3 min, and the predicted values were calculated. One hour before, the athletes answered the Pittsburgh Sleep Quality Index (PSQI) questionnaire. The results showed a difference between groups (injury vs. no-injury) in O (7.5 ± 1.4 vs. 5.5 ± 1.2 mL/min/kg, < 0.001) and percent of predicted values (92.5 ± 17.2 vs. 68.3 ± 14.6%, < 0.001) and HR, such as beats per min (100.6 ± 12.8 vs. 93.1 ± 4.6 bpm, = 0.001), percent of predicted values (50.7 ± 6.4 vs. 47.6 ± 2.8%, = 0.003) and sleep quality score (PSQI: 4.9 ± 2.2 vs. 3.1 ± 0.9, = 0.005). Anthropometric characteristics were not different between groups. Oxygen consumption and heart rate at rest are affected by the systemic adaptations due to injury. These pathophysiological changes probably relate to increased blood flow in an attempt to restore the injury area.
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http://dx.doi.org/10.3390/ijerph17134810DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7370061PMC
July 2020

Common variable immunodeficiency and asthma: Coexistence or coincidence?

Ann Allergy Asthma Immunol 2020 06;124(6):635

Department of Respiratory Medicine, Faculty of Medicine, University of Thessaly, Larissa, Greece. Electronic address:

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http://dx.doi.org/10.1016/j.anai.2020.02.013DOI Listing
June 2020

Concurrent cardiac sarcoidosis and obstructive sleep apnea presenting as arrhythmias.

BMC Pulm Med 2020 May 8;20(1):132. Epub 2020 May 8.

Respiratory Medicine Department, University of Thessaly School of Medicine, University Hospital of Larissa, Mezourlo (Biopolis), 41110, Larissa, Greece.

Background: Cardiac involvement is a rare and potentially fatal presentation of sarcoidosis. Obstructive sleep apnea may complicate sarcoidosis.

Case Presentation: We report a case of a sarcoidosis patient with cardiac involvement presenting with ventricular arrhythmias. Besides medical and invasive measures of therapy, the patient failed to respond fully. The patient was subjected to overnight polysomnography and diagnosed with concurrent obstructive sleep apnea syndrome. Following continuous positive airway pressure therapy, we observed a significant improvement of ventricular arrhythmias while methylprednisolone was further tapered.

Conclusions: To our knowledge, this is the first report of cardiac sarcoidosis further implicated by OSAHS and presenting as ventricular arrhythmias that underlies the need for extensive testing in cardiac sarcoidosis in patients not responding to immunosuppressive therapy.
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http://dx.doi.org/10.1186/s12890-020-1163-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7210663PMC
May 2020

Clinical profile of severe asthmatics receiving biological treatment: see behind the scenes.

J Asthma 2020 Apr 14:1-3. Epub 2020 Apr 14.

Department of Respiratory Medicine, Faculty of Medicine, University of Thessaly, Larissa, Greece.

The clinical phenotyping of severe asthma could improve treatment outcomes, quality of life, morbidity, and mortality of asthma patients. The growing availability of rich clinical data could provide opportunities to address a broad range of real-world questions regarding clinical phenotyping and effective therapeutic approaches of severe asthma. Accordingly, in this Letter to the Editor, we provide data relevant to constructing the clinical profile of a Greek severe asthma patient cohort who receive biological treatment.
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http://dx.doi.org/10.1080/02770903.2020.1750629DOI Listing
April 2020

Enhanced Public Interest in Response to the Refugee and Healthcare Crises in Greece.

Int J Environ Res Public Health 2020 03 27;17(7). Epub 2020 Mar 27.

Department of Respiratory Medicine, Faculty of Medicine, University of Thessaly, BIOPOLIS, 41110 Larissa, Greece.

: The Greek National Health System (NHS) has been profoundly affected by the synergy of the economic and refugee crises. We aimed at evaluating the public interest regarding refugee and healthcare issues in Greece. : Google Trends was employed to normalize traffic data on a scale from 0 to 100, presented as monthly relative search volume (RSV) for the search term queries: "refugees", "health", "diseases", "hospital", and "economic crisis" in Greece, from the period 2008 to 2020. Cross-country comparisons in selected European countries were made. : The analysis of RSV data showed an upward trend for the keyword "refugee", in Greece, in the last five years, with two remarkable peaks from 2015 to 2016 and from 2019 to the present. Interest regarding refugees was more prevalent in the Aegean islands compared to the mainland. The mass influx of refugees has been linked to disease-related concerns. The search terms "hospital" and "health" have been the most popular and constantly quested topics since the beginning of the economic crisis in Greece, in 2009. Similar trends existed across Europe. : There is an urgent need for effective public awareness of current politico-ethical and social-economic conditions. The patterns of public interest can formulate public policy.
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http://dx.doi.org/10.3390/ijerph17072272DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7177306PMC
March 2020

Malignant mesothelioma cells secrete natriuretic peptides: Data and diagnostic clinical implications.

Respirology 2020 10 2;25(10):1060-1065. Epub 2020 Mar 2.

Intensive Care Unit, University Hospital of Larissa, Faculty of Medicine, University of Thessaly, Larissa, Greece.

Background And Objective: Mesothelial cells and cardiomyocytes have shared embryonic mesodermal origin. Cardiomyocytes release BNP under stretch. We searched whether malignant mesothelioma cells also secrete BNP and if so, this has a meaningful impact.

Methods: Part I: Prospectively, patients with pleural lesions on CT having malignant mesothelioma effusions (MME, n = 13) were compared to patients with malignant effusions with pleural lesions (MEa, n = 14). Age-matched patients with ME without pleural lesions (MEb, n = 16) and non-malignant effusions (NME, n = 25) were analysed. Part II: Retrospectively, samples from patients with mesothelioma (n = 14), lung cancer (n = 8) or heart failure (n = 9) were used. BNP was measured in pleural fluid and blood/plasma. Part III: BNP was assessed in the culture supernatants of benign (MeT-5A) and malignant mesothelioma cell lines (M14K-epithelioid, MSTO-biphasic and ZL34-sarcomatoid) (n = 10 per cell line in three different biological replicates).

Results: In vitro, BNP concentration was significantly higher in the supernatant of all malignant cell lines than benign ones (P < 0.01), denoting BNP's production from the former. The pleural fluid to blood BNP ratio in MME was extremely high in Part I and Part II subjects (28.3 ± 12.1 and 25.9 ± 8.6, respectively) versus 1.1 ± 0.3 and 0.4 ± 0.1 in Part I ME and NME, respectively (P < 0.0001), and 0.8 ± 0.1 and 0.4 ± 0.1 in Part II ME and NME, respectively (P < 0.0001). BNP ratio ≥2.11 in Part I had 92% sensitivity and 94.5% specificity for MME (P < 0.0001).

Conclusion: BNP is secreted from malignant mesothelial cells. In clinical practice, the pleural fluid to blood BNP ratio can help in the diagnosis of malignant mesothelioma.
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http://dx.doi.org/10.1111/resp.13788DOI Listing
October 2020