Long-term outcome of screening for polyoma BK virus infection in kidney transplant recipients

BK virus (BKV) infection was studied prospectively in 50 unselected consecutive patients who had undergone kidney transplantation. Infection was monitored for one year after transplantation. Viral DNA in urine (viruria) and plasma (viremia) samples was detected by nested, qualitative polymerase chain reaction. BKV screening data was available for 92% (n = 46) of patients enrolled in the study. Four groups of patients were distinguished: uninfected patients (group 1, n = 30), patients with viruria (group 2, n = 3), patients with viremia (group 3, n = 6) and patients with developed BKV nephropathy (group 4, n = 7). Infection was observed starting form the first month, and the maximum number of patients with active BKV infection occurred at six months after transplantation. Five-year graft survival was 69% for patients with any evidence of BKV infection, compared with 80.0% (P = NS) for patients without BKV infection. The best graft function was observed in group one patient (mean serum creatinine 130 mkmol/l and glomerular filtration rate (GFR) 60.9 ml/min) and the worst in group 4 (mean serum creatinine 180 mkmol/l and GFR 52.31 ml/min) at five years after transplantation. Five-year patient survival was 82.6% and was not affected by presence of BKV infection.publishersversionPeer reviewe

Interleukin-6 in Synovial Fluid as a Tool for Differentiation of Inflammation and Degeneration in Chronic Synovitis and Treatment Selection

Although Osteoarthritis (OA) is a widespread type of arthritis, no cure or medication can halt its natural progression. Only weight loss and physiotherapy can help to relieve pain and preserve function. Chronic un-inflammatory synovitis is not uncommon in OA; however, Inflammatory Arthritis (IA) can also start in middle-aged adults affected by OA. Pain and swelling of the joints, especially in the knee joints, are usual complaints in rheumatological practice where the primary treatment for chronic inflammatory arthritis is disease-modifying antirheumatic drugs (DMARDs). At the same time, persistent chronic synovitis leads to secondary OA due to inflammation, aging, and other factors. Discrimination between chronic synovitis due to inflammation or degeneration poses a significant challenge, especially when specific markers for IA are negative. Interleukin-6 (IL-6) has been a research topic for many scientific publications over the past several years. Although IL-6 production and signaling have been observed in OA, a recently published article shows much more elevated IL-6 concentration in synovial fluid (SF) of symptomatic joints in different types of IA [1]. We decided to clarify the importance of IL-6 concentration in synovial fluid (SF) for diagnostic and treatment purposes.publishersversionPeer reviewe

COVID-19 Pandemic-Revealed Consistencies and Inconsistencies in Healthcare : A Medical and Organizational View

Funding Information: Funding: The study was supported by the Latvian Council of Science, Fundamental and Applied Research project, No. lzp‐2019/1‐0380, ‘Selection of biomarkers in ME/CFS for patient stratification and treatment surveillance/optimisation’. Publisher Copyright: © 2022 by the authors. Li-censee MDPI, Basel, Switzerland.The circumstances of the Coronavirus disease caused by the SARS-CoV-2 virus (COVID-19) pandemic have had a significant impact on global and national developments, affecting the existence of society in all its expressions, as well as the lives of people themselves. In the context of the pandemic, increased attention has been focused on acute measures, but the ending of the pandemic is expected as a resolution of the related healthcare problems. However, there are several indicators that the COVID-19 pandemic might induce long-term consequences for individual and public health. Some of the consequences are inferred and predictable, but there are also areas of medicine that have been indirectly affected by the pandemic, and these consequences have not yet been sufficiently explored. This study is focused on drawing attention to some of the COVID-19 pandemic consistencies and the pandemic-revealed inconsistencies in healthcare. Content analysis and statistical analysis were applied to achieve the aim of the study. The main findings of the study address chronic disease burden (particularly, myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS)), healthcare governance and organizational issues, and the synergy between health policy perspectives and innovative solutions in practice. The study provides insight into the particular healthcare issues affected by the COVID-19 pandemic, such as the increase in mortality in some diagnoses besides COVID-19 and the possible emergence of a new type of resistance— vaccine-resistance—contemporaneously supporting the identification of the tendencies and currently unnoticed indirect consistencies and inconsistencies revealed by the pandemic.publishersversionPeer reviewe

Human herpesvirus-6 and-7 in the brain microenvironment of persons with neurological pathology and healthy people

Funding Information: This research was supported by the Latvian Council of Science Grant Nr.478/2012 and fundamental and applied research project of the Latvian Council of Science LZP-2020/2-0069. The authors would like to thank Svetlana Chapenko for nPCR data curation, and Silvija Roga, certified pathologist, and Ojars Teteris certified pathologist, for collecting of study material. Publisher Copyright: © 2021 by the authors. Licensee MDPI, Basel, Switzerland.During persistent human beta-herpesvirus (HHV) infection, clinical manifestations may not appear. However, the lifelong influence of HHV is often associated with pathological changes in the central nervous system. Herein, we evaluated possible associations between immunoex-pression of HHV-6,-7, and cellular immune response across different brain regions. The study aimed to explore HHV-6,-7 infection within the cortical lobes in cases of unspecified encephalo-pathy (UEP) and nonpathological conditions. We confirmed the presence of viral DNA by nPCR and viral antigens by immunohistochemistry. Overall, we have shown a significant increase (p < 0.001) of HHV antigen expression, especially HHV-7 in the temporal gray matter. Although HHV-infected neurons were found notably in the case of HHV-7, our observations suggest that higher (p < 0.001) cell tropism is associated with glial and endothelial cells in both UEP group and controls. HHV-6, predominantly detected in oligodendrocytes (p < 0.001), and HHV-7, predominantly detected in both astrocytes and oligodendrocytes (p < 0.001), exhibit varying effects on neural homeostasis. This indicates a high number (p < 0.001) of activated microglia observed in the temporal lobe in the UEP group. The question remains of whether human HHV contributes to neurological diseases or are markers for some aspect of the disease process.Peer reviewe

Detection and genotyping of human papillomavirus in hypopharyngeal carcinoma samples

Publisher Copyright: © 2021 Sciendo. All rights reserved.The incidence of hypopharyngeal cancer globally is about 0.8 per 100 000. Globally, approximately 38 000 cases of head and neck cancer are considered yearly to be high-risk human papillomavirus (HR-HPV) related. Biopsy material fixation in formalin and embedding in paraffin (FFPE) creates many challenges. The extraction of nucleic acid material requires a more complicated approach, and often the extracted DNA is fragmented. The aim of the study was to compare several HR-HPV detection methods in nucleic acid material extracted from FFPE samples. The extracted DNA was analysed with different molecular biology methods to assess DNA quality and to determine the presence of HPV DNA with various HPV detection systems. The results were compared and statistically analysed. There was good agreement between two real-time PCR methods — Anyplex II HPV28 and Sacace HPV High-Risk Screen Real-TM Quant. We failed to reach a conclusion on agreement between real-time PCR methods and HPV16 type-specific primer PCR. There was moderate positive correlation between Anyplex II HPV28 semiquantitative results and Sacace quantitative results. We suggest that real-time PCR assays detecting smaller DNA amplicons are good and reliable methods for detecting HPV genetic material in FFPE samples.Peer reviewe

Significance of hypouricaemia in the development of neurodegenerative diseases

Publisher Copyright: © 2021 Sciendo. All rights reserved.Hypouricaemia has received relatively little attention in the literature. As a result, there is lessawareness or understanding of the potential risks of low uric acid levels. Emerging research indi-cates that normal uric acid levels may have an antioxidative and neuroprotective effect. Thisstudy aims to investigate possible associations between hypouricaemia and neurodegenerativedisease. Data was collected from seventy-seven outpatients and inpatients who underwent rou-tine uric acid testing, who were then stratified into patients with and without neurodegenerativedisease. Patients with renal pathologies and patients using uric acid altering medications were ex-cluded from the study. There was a significant difference in the prevalence of Alzheimer’s diseasebetween hypouricemic and normouricemic patients (p= 0.001), however there was no differencein the prevalence of vascular dementia (p= 0.45). This study provides evidence that hypouricae-mia has potential effects on health, specifically on the rate of neurodegenerative diseases suchas Alzheimer’s disease and gives weight to the potential neuroprotective role of uric acid.publishersversionPeer reviewe

Immunological Aspects of EBV and Oral Mucosa Interactions in Oral Lichen Planus

Funding Information: VirA project Nr. 952376. Publisher Copyright: © 2023 by the authors.Oral lichen planus (OLP) is considered a T cell-mediated chronic inflammatory process activated by an unknown antigen, making basal keratinocytes vulnerable to a cytotoxic cell mediated immune response. The aim of this review is to summarize information on the role and pathways of Epstein–Barr virus (EBV) and immune cells in inducing OLP as an autoimmune lesion. The pathogenesis of OLP is analyzed from immunological aspects of interactions between EBV and oral mucosa. The results of the available studies allow us to assume that EBV can act both as an exogenous and an endogenous antigen in the pathogenesis of OLP. We emphasized the role of antigen-presenting cells (APC), such as dendritic cells (Langerhans cells, LC), in detecting and capturing antigens and modulating the adaptive immune response. Although EBV shows tropism for B cells and epithelial cells, under certain conditions it can infect monocytes, LCs, NK, and T lymphocytes. It means that under some circumstances of the chronic inflammatory process, EBV particles can react as endogenous agents. During the development of the autoimmune process, a decisive role is played by the loss of immune tolerance. Factors like the activity of cytokines, chemokines, and autoantibodies secreted by EBV-positive plasma cells, autoantigens formed due to virus protein mimicry of human proteins, new self-peptides released from damaged tissues, self-reactive B and T cells, dysregulation of LC function, the anti-apoptotic effect of EBV early lytic antigens, and an imbalance between inflammatory and anti-inflammatory immune cells facilitate the development of an autoimmune process.publishersversionPeer reviewe

Alcohol-Induced Alterations in the Vascular Basement Membrane in the Substantia Nigra of the Adult Human Brain

Funding Information: Funding: This research was funded by the Latvian Council of Science, “The Role of Human Herpesvirus-6t Infection and Alcohol Abuse in the Development of Neuroinflammation”, project no. lzp-2020/2-0069. Publisher Copyright: © 2022 by the authors. Licensee MDPI, Basel, Switzerland.The blood–brain barrier (BBB) represents a highly specialized interface that acts as the first line of defense against toxins. Herein, we investigated the structural and ultrastructural changes in the basement membrane (BM), which is responsible for maintaining the integrity of the BBB, in the context of chronic alcoholism. Human post-mortem tissues from the Substantia Nigra (SN) region were obtained from 44 individuals, then grouped into controls, age-matched alcoholics, and non-age-matched alcoholics and assessed using light and electron microscopy. We found significantly less CD31+ vessels in alcoholic groups compared to controls in both gray and white matter samples. Alcoholics showed increased expression levels of collagen-IV, laminin-111, and fibronectin, which were coupled with a loss of BM integrity in comparison with controls. The BM of the gray matter was found to be more disintegrated than the white matter in alcoholics, as demonstrated by the expression of both collagen-IV and laminin-111, thereby indicating a breakdown in the BM’s structural composition. Furthermore, we observed that the expression of fibronectin was upregulated in the BM of the white matter vasculature in both alcoholic groups compared to controls. Taken together, our findings highlight some sort of aggregation or clumping of BM proteins that occurs in response to chronic alcohol consumption.publishersversionPeer reviewe

Shadow burden of undiagnosed myalgic encephalomyelitis/chronic fatigue syndrome (Me/cfs) on society : Retrospective and prospective—in light of covid-19

Publisher Copyright: © 2021 by the authors. Licensee MDPI, Basel, Switzerland.Background: Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a poorly understood, complex, multisystem disorder, with severe fatigue not alleviated by rest, and other symptoms, which lead to substantial reductions in functional activity and quality of life. Due to the unclear aetiology, treatment of patients is complicated, but one of the initial problems is the insufficient diagnostic process. The increase in the number of undiagnosed ME/CFS patients became specifically relevant in the light of the COVID-19 pandemic. The aim of this research was to investigate the issues of undiagnosed potential ME/CFS patients, with a hypothetical forecast of the expansion of post-viral CFS as a consequence of COVID-19 and its burden on society. Methods: The theoretical research was founded on the estimation of classic factors presumably affecting the diagnostic scope of ME/CFS and their ascription to Latvian circumstances, as well as a literature review to assess the potential interaction between ME/CFS and COVID-19 as a new contributing agent. The empirical study design consisted of two parts: The first part was dedicated to a comparison of the self-reported data of ME/CFS patients with those of persons experiencing symptoms similar to ME/CFS, but without a diagnosis. This part envisaged the creation of an assumption of the ME/CFS shadow burden “status quo”, not addressing the impact of COVID-19. The second part aimed to investigate data from former COVID-19 patients’ surveys on the presence of ME/CFS symptoms, 6 months after being affected by COVID-19. Descriptive and analytical statistical methods were used to analyse the obtained data. Results: The received data assumed that the previously obtained data on the ME/CFS prevalence of 0.8% in the Latvian population are appropriate, and the literature review reports a prevalence of 0.2–1.0% in developed countries. Regarding the reciprocity of ME/CFS and COVID-19, the literature review showed a lack of research in this field. The empirical results show quite similar self-esteem among ME/CFS patients and undiagnosed patients with longstanding disease experience, while former COVID-19 patients show a significantly lower severity of these problems. Notably, “psychological distress (anxiety)” and “episodic fatigue” are significantly predominant symptoms reported by former COVID-19 patients in comparison with ME/CFS patients and undiagnosed patients prior to the COVID-19 pandemic. The results of our analysis predict that the total amount of direct medical costs for undiagnosed patients (out-of-pocket payments) is more than EUR 15 million p.a. (in Latvia), and this may increase by at least 15% due to the consequences of COVID-19. Conclusions: ME/CFS creates a significant shadow burden on society, even considering only the direct medical costs of undiagnosed patients—the number of whom in Latvia is probably at least five times higher than the number of discerned patients. Simultaneously, COVID-19 can induce long-lasting complications and chronic conditions, such as post-viral CFS, and increase this burden. The Latvian research data assume that ME/CFS patients are not a high-risk group for COVID-19; however, COVID-19 causes ME/CFS-relevant symptoms in patients. This increases the need for monitoring of patients for even longer after recovering from COVID-19′s symptoms, in order to prevent complications and the progression of chronic diseases. In the context of further epidemiological uncertainty, and the possibility of severe post-viral consequences, preventive measures are becoming significantly more important; an integrated diagnostic approach and appropriate treatment could reduce this burden in the future.publishersversionPeer reviewe

Assessment of HHV-6 and HHV-7 in patients after kidney transplantation

Human herpesviruses HHV-6 and HHV-7 reactivation in transplantation is associated with indirect immunomodulatory effects, such as cytomegalovirus (CMV) disease, increased opportunistic infections, graft dysfunction and acute rejection (AR). In this study, we analysed the clinical and immunological outcomes in renal transplant recipients (RTR) with active HHV-6 and HHV-7 infection. Between January 2007 and December 2007, clinical, virological and immunological tests were carried out in 46 RTR. The patients were divided into three groups: with active HHV-6 infection; with active HHV-7 infection; and without infection (control). The mean follow-up was 14 ± 2.5 months. At three months after renal transplantation (RT), active CMV infection was present in 12 (26%); HHV-6 in four (8.6%); and HHV-7 in nine (19.5%) of RTR. Active ß-herpesviruses infection was not associated with more frequent AR and worsening of graft function in recipients at different times after RT. The lymphocyte subsets (CD3+; CD4+ and CD8+ cell count) were considerably lower in RTR before RT. At 3 months after RT CD19+ and CD25+ cell counts were significantly increased in the HHV-7 group compared with the control group (P < 0.05). Significant differences were not found in clinical and immunological outcomes between patients with active ß-herpesviruses infection and those without active ß-herpesviruses infection.publishersversionPeer reviewe