Targeting microbiota : What do we know about it at present?

Publisher Copyright: © 2019 by the authors. Licensee MDPI, Basel, Switzerland.The human microbiota is a variety of different microorganisms. The composition of microbiota varies from host to host, and it changes during the lifetime. It is known that microbiome may be changed because of a diet, bacteriophages and different processes for example, such as inflammation. Like all other areas of medicine, there is a continuous growth in the area of microbiology. Different microbes can reside in all sites of a human body, even in locations that were previously considered as sterile; for example, liver, pancreas, brain and adipose tissue. Presently one of the etiological factors for liver disease is considered to be pro-inflammatory changes in a host’s organism. There are lot of supporting data about intestinal dysbiosis and increased intestinal permeability and its effect on development of liver disease pointing to the gut–liver axis. The gut–liver axis affects pathogenesis of many liver diseases, such as chronic hepatitis B, chronic hepatitis C, alcoholic liver disease, non-alcoholic liver disease, non-alcoholic steatohepatitis, liver cirrhosis and hepatocellular carcinoma. Gut microbiota has been implicated in the regulation of brain health, emphasizing the gut–brain axis. Also, experiments with mice showed that microorganisms have significant effects on the blood–brain barrier integrity. Microbiota can modulate a variety of mechanisms through the gut–liver axis and gut–brain axis. Normal intestinal flora impacts the health of a host in many positive ways, but there is now significant evidence that intestinal microbiota, especially altered, have the ability to impact the pathologies of many diseases through different inflammatory mechanisms. At this point, many of the pathophysiological reactions in case of microbial disbyosis are still unclear.publishersversionPeer reviewe

Vaccine Vigilance System : Considerations on the Effectiveness of Vigilance Data Use in COVID-19 Vaccination

FARP project "Selection of biomarkers in ME/CFS for patient stratification and treatment surveillance / optimisationi".(1) Background: The safety of medicines has been receiving increased attention to ensure that the risks of taking medicines do not outweigh the benefits. This is the reason why, over several decades, the pharmacovigilance system has been developed. The post-authorization pharmacovigilance system is based on reports from healthcare professionals and patients on observed adverse reactions. The reports are collected in databases and progressively evaluated. However, there are emerging concerns about the effectiveness of the established passive pharmacovigilance system in accelerating circumstances, such as the COVID-19 pandemic, when billions of doses of new vaccines were administered without a long history of use. Currently, health professionals receive fragmented new information on the safety of medicines from competent authorities after a lengthy evaluation process. Simultaneously, in the context of accelerated mass vaccination, health professionals need to have access to operational information—at least on organ systems at higher risk. Therefore, the aim of this study was to perform a primary data analysis of publicly available data on suspected COVID-19 vaccine-related adverse reactions in Europe, in order to identify the predominant groups of reported medical conditions after vaccination and their association with vaccine groups, as well as to evaluate the data accessibility on specific syndromes. (2) Methods: To achieve the objectives, the data publicly available in the EudraVigilance European Database for Suspected Adverse Drug Reaction Reports were analyzed. The following tasks were defined to: (1) Identify the predominant groups of medical conditions mentioned in adverse reaction reports; (2) determine the relative frequency of reports within vaccine groups; (3) assess the feasibility of obtaining information on a possibly associated syndrome—myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). (3) Results: The data obtained demonstrate that the predominant medical conditions induced after vaccination are relevant to the following categories: (1) “General disorders and administration site conditions”, (2) “nervous system disorders”, and (3) “musculoskeletal and connective tissue disorders”. There are more reports for mRNA vaccines, but the relative frequency of reports per dose administered, is lower for this group of vaccines. Information on ME/CFS was not available, but reports of “chronic fatigue syndrome” are included in the database and accessible for primary analysis. (4) Conclusions: The information obtained on the predominantly reported medical conditions and the relevant vaccine groups may be useful for health professionals, patients, researchers, and medicine manufacturers. Policymakers could benefit from reflecting on the design of an active pharmacovigilance model, making full use of modern information technologies, including big data analysis of social media and networks for the detection of primary signals and building an early warning system.publishersversionPeer reviewe

Myalgic encephalomyelitis/chronic fatigue Syndrome (ME/CFS) : Investigating care practices pointed out to disparities in diagnosis and treatment across European Union

Funding Information: Funding: EUROMENE Network was funded by the COoperation in Science and Technology (COST) program from Utopian Commission (COST#15111). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Publisher Copyright: Copyright: © 2019 Strand et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Copyright: Copyright 2020 Elsevier B.V., All rights reserved.ME/CFS is a chronic, complex, multisystem disease that often limits the health and functioning of the affected patients. Diagnosing patients with ME/CFS is a challenge, and many different case definitions exist and are used in clinical practice and research. Even after diagnosis, medical treatment is very challenging. Symptom relief and coping may affect how patients live with their disease and their quality of life. There is no consensus on which diagnostic criteria should be used and which treatment strategies can be recommended for patients. The purpose of the current project was to map the landscape of the Euromene countries in respect of national guidelines and recommendations for case definition, diagnosis and clinical approaches for ME/CFS patients. A 23 items questionnaire was sent out by email to the members of Euromene. The form contained questions on existing guidelines for case definitions, treatment/management of the disease, tests and questionnaires applied, and the prioritization of information for data sampling in research. We obtained information from 17 countries. Five countries reported having national guidelines for diagnosis, and five countries reported having guidelines for clinical approaches. For diagnostic purposes, the Fukuda criteria were most often recommended, and also the Canadian Consensus criteria, the International Consensus Criteria and the Oxford criteria were used. A mix of diagnostic criteria was applied within those countries having no guidelines. Many different questionnaires and tests were used for symptom registration and diagnostic investigation. For symptom relief, pain and anti-depressive medication were most often recommended. Cognitive Behavioral Therapy and Graded Exercise treatment were often recommended as disease management and rehabilitative/palliative strategies. The lack of consistency in recommendations across European countries urges the development of regulations, guidance and standards. The results of this study will contribute to the harmonization of diagnostic criteria and treatment for ME/CFS in Europe.Peer reviewe

HLA Class II-DRB,-DQA and-DQB genotypes in peripheral blood shows shifts during the course of sepsis

Publisher Copyright: © 2019 Linda BÄra et al. published by Sciendo. Copyright: Copyright 2019 Elsevier B.V., All rights reserved.Undeniably, sepsis is still a profoundly damaging and life-threatening condition for many individuals. With multiple changes in sepsis patients it is difficult to precisely classify an individual's response in sepsis as proinflammatory or immunosuppressed. The aim of this study was to investigate genetically determined predisposition to developed sepsis by analysis of distribution of human leukocyte antigen (HLA) class II genes. Samples from patients with sepsis were collected at Pauls Stradiņš Clinical University Hospital, Latvia, in an intensive care unit between October 2016 and May 2017. The study group included 62 patients with sepsis, who were genotyped for HLA-DR; DQ using real time polymerase chain reaction-sequence specific primer (RT PCR-SSP). As a control group, data of 100 individuals were taken from the genetic bank of RSU Joint Laboratory of Clinical Immunology and Immunogenetics. The summarised results showed that the frequency of alleles DRB1∗04:01 (OR = 5.54; 95% CI = 1.88-16.29); DRB1∗07:01 (OR = 19.03; 95% CI = 2/37-152.82); DQA1∗05:01 (OR = 14.17; 95% CI = 5.67-35.4); and DQB1∗02:01 (OR = 50.00; 95% CI = 2.90-861.81) were significantly increased in patients with sepsis compared to the control group patients. The frequency of DRB1∗16:01 (OR = 0.17, 95% CI = 0.04-0.59); DRB1∗17:01 (OR = 0.04; 95% CI = 0.00-0.69); DQA1∗01:01 (OR = 0.04; 95% CI = 0.00-0.31); DQA1∗01:02 (OR = 0.03; 95% CI = 0.00-0.23); DQB1∗02:02 (OR = 0.12; 95% CI = 0.03-0.42) alleles was lower in sepsis patients than in control subjects. The most frequent HLA-DRB1/DQA1/DQB1 haplotypes that was significantly increased in patients with sepsis were: DRB1∗01:01/DQA1∗05:01/DQB1∗03:01 (OR = 12.6; 95% CI = 1.51-105.0; p < 0.003). Sepsis patients with pneumonia and alleles and DRB1 04:01; 07:01, DQB1 02:01 had the highest mortality rate. Undoubtedly, our preliminary data showed that development of sepsis can be associated with alleles and haplotypes of HLA class II genes. For more precise conclusion the research should be continued to include a larger patient group.Peer reviewe

The Advantages of an Integrative Approach in the Primary Healthcare of Post-COVID-19 and ME/CFS Patients

The coronavirus disease caused by the SARS-CoV-2 virus (COVID-19) pandemic has changed not only global epidemiological and economic developments but also the lives of every individual, with particular severity for patients. The number of acute illness cases grew rapidly, significantly increasing the workload of hospitals, and simultaneously, new chronic diseases emerged, such as persistent post-COVID-19 syndrome (PPCS), with unclear etiology, symptoms, and complexity—similar to myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). Accordingly, the burden of chronic diseases poses new long-term challenges for primary healthcare and requires new approaches to patient care. This chapter provides insight into the integrative approach to healthcare and focuses on potentially new solutions by implementing an integrative attitude to the treatment of post-COVID-19 and ME/CFS patients in primary healthcare. Integrative health coaching contributes the holistic approach to patients’ overall health and resilience through cognitive practice and patient active engagement. The findings of this chapter can enrich the person-centered approach and healthcare system strengthening through holistic measures and systems thinking

Higher CTX-M, TEM, and SHV extended-spectrum beta-lactamase plasmid gene combination frequency in ESBL producing Klebsiella pneumoniae compared with ESBL producing Escherichia coli

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The role of HHV-6 and HHV-7 infections in the development of fibromyalgia

Funding Information: Funding The work was supported by the project RSU ZP 13/2013: BAssociation of fibromyalgia and myalgic encephalomyelitis/chronic fatigue syndrome with beta-herpesviruses (HHV-6A, HHV-6B, HHV-7) and parvovirus B19 infection^ (SC). Publisher Copyright: © 2019, The Author(s). Copyright: Copyright 2020 Elsevier B.V., All rights reserved.Human herpes virus-6 (HHV-6) and human herpes virus-7 (HHV-7) are immunomodulating viruses potentially affecting the nervous system. We evaluated the influence of HHV-6 and HHV-7 infections on fibromyalgia (FM) clinical course. Forty-three FM patients and 50 control group participants were enrolled. 39.50% (n = 17) FM patients had light A delta and C nerve fiber damage, 27.91% (n = 12) had severe A delta and C nerve fiber damage. 67.44% (n = 29) FM patients had loss of warm sensation in feet, loss of heat pain sensation, and increased cold pain sensation (34.90%, n = 15 in both findings). HHV-6 and HHV-7 genomic sequences in peripheral blood DNA in 23/43 (51.00%) and 34/43 (75.50%) of samples from FM patients and in 3/50 (6.00%) and 26/50 (52.00%) of samples from the control group individuals were detected. Active HHV-6 (plasma viremia) or HHV-7 infection was revealed only in FM patients (4/23, 17.40% and 4/34, 11.80%, respectively). A statistically significant moderate positive correlation was found between A delta and C nerve fiber damage severity and HHV-6 infection (p < 0.01, r = 0.410). 23/43 patients from the FM group and control group participants HHV-6 and 34/45 HHV-7 did have infection markers. A statistically significant moderate positive correlation was found between A delta and C nerve fiber damage severity and HHV-6 infection (p < 0.01, r = 0.410). No difference was found between detection frequency of persistent HHV-6 and HHV-7 infection between FM patients and the control group. Statistically significant correlation was observed between quantitation of changes in QST thermal modalities and HHV-6 infection. There was no correlation between A delta and C nerve fiber damage and HHV-7 infection.Peer reviewe

Immunogenetic markers definition in latvian patients with lyme borreliosis and lyme neuroborreliosis

Funding Information: This work was supported by the European Social Fund (ESF) project ?Support for doctoral study program and scientific degree receiving in Riga Stradi?? University, agreement No. 2009/0147/1DP/1.1.2.1.2/09/IPIA/VIAA/009?. Publisher Copyright: © 2016 by the authors; licensee MDPI, Basel, Switzerland. Copyright: Copyright 2017 Elsevier B.V., All rights reserved.The aim of this study was to determine the human leukocyte antigen (HLA)-DRB1 alleles in two groups of patients in Latvia: patients with Lyme borreliosis and patients with Lyme neuroborreliosis. The study included 216 patients with Lyme borreliosis, 29 patients with Lyme neuroborreliosis and 282 control persons. All surveyed persons were residents of Latvia. The HLA-DR genotyping was performed by polymerase chain reaction-sequence specific primer (PCR-SSP). The predisposition to the Lyme borreliosis is associated with the HLA-DRB1*07, -DRB1*17(03), -DRB1*04, -DRB1*15(02) alleles. The allele -DRB1*11(05), -DRB1*14(06) and -DRB1*13(06) were significantly more frequent in controls. In-group with Lyme neuroborreliosis differences were found for the -DRB1*07 and -DRB1*04 alleles, but only HLA-DRB1*07 allele was statistically significant after Bonferroni correction and associated with Lyme neuroborreliosis in Latvian patients.Peer reviewe

Biomarkers in the diagnostic algorithm of myalgic encephalomyelitis/chronic fatigue syndrome

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a complex disease that is mainly diagnosed based on its clinical symptoms. Biomarkers that could facilitate the diagnosis of ME/CFS are not yet available; therefore, reliable and clinically useful disease indicators are of high importance. The aim of this work was to analyze the association between ME/CFS clinical course severity, presence of HHV-6A/B infection markers, and plasma levels of autoantibodies against adrenergic and muscarinic acetylcholine receptors. A total of 134 patients with ME/CFS and 33 healthy controls were analyzed for the presence of HHV-6A/B using PCRs, and antibodies against beta2-adrenergic receptors (β2AdR) and muscarinic acetylcholine receptors (M3 AChR and M4 AChR) using ELISAs. HHV-6A/B U3 genomic sequence in whole-blood DNA was detected in 19/31 patients with severe ME/CFS, in 18/73 moderate ME/CFS cases, and in 7/30 mild ME/CFS cases. Severity-related differences were found among those with a virus load of more than 1,000 copies/106 PBMCs. Although no disease severity-related differences in anti-β2AdR levels were observed in ME/CFS patients, the median concentration of these antibodies in plasma samples of ME/CFS patients was 1.4 ng/ml, while in healthy controls, it was 0.81 ng/ml, with a statistically significant increased level in those with ME/CFS (p = 0.0103). A significant difference of antibodies against M4 AChR median concentration was found between ME/CFS patients (8.15 ng/ml) and healthy controls (6.45 ng/ml) (p = 0.0250). The levels of anti-M4 plotted against disease severity did not show any difference; however, increased viral load correlates with the increase in anti-M4 level. ME/CFS patients with high HHV-6 load have a more severe course of the disease, thus confirming that the severity of the disease depends on the viral load—the course of the disease is more severe with a higher viral load. An increase in anti-M4 AchR and anti-β2AdR levels is detected in all ME/CFS patient groups in comparison to the control group not depending on ME/CFS clinical course severity. However, the increase in HHV-6 load correlates with the increase in anti-M4 level, and the increase in anti-M4 level, in turn, is associated with the increase in anti-β2AdR level. Elevated levels of antibodies against β2AdR and M4 receptors in ME/CFS patients support their usage as clinical biomarkers in the diagnostic algorithm of ME/CFS.publishersversionPeer reviewe

Coaching to strengthen critical success factors in integrative care for chronic fatigue patients: the Patient Needs-Resources Model

Theoretical and empirical studies discover that an integrative approach is particularly important in chronic disorders and multiple long-term conditions, such as chronic fatigue. Chronic fatigue syndrome (CFS) is a classic example of a potentially severe, multisystemic illness with a wide diversity of symptoms and the corresponding diagnostic complexity. The prevalence of CFS-like syndromes expanded in the context of the COVID-19 pandemic, increasing the disorder and treatment burden. Thus, this article aimed to draw attention to the possibilities to strengthen the integrative approach to diagnosing and treating chronic disorders and multiple long-term conditions. The main critical success factors identified for integrative approaches were: a holistic approach, that provides a more comprehensive diagnostic and personalized treatment strategy, a multidisciplinary team, and patient engagement. The strengths and weaknesses of these factors were explored and coaching was identified as a potential unifying and reinforcing element. Coaching has a wide spectrum of manifestations clearly representing a holistic approach, that has been successfully used in multidisciplinary team building. Moreover, coaching exposes support addressing the patient engagement issues identified by the Patient Needs-Resources Model (PN-R Model) such as low levels of self-efficacy, optimism, and subjective well-being. Coaching may assist patients to identify and prioritize their goals, becoming aware of their personal resources, developing strategies for managing symptoms, and building skills to increase their self-efficacy and active engagement in the treatment process. Therefore, the authors emphasize coaching as a perspective element of optimization of patient care, that requires additional theoretical and long-term empirical research