For many years the neuromodulator adenosine has been recognized as an endogenous anticonvulsant molecule and termed a “retaliatory metabolite.” As the core molecule of ATP, adenosine forms a unique link between cell energy and neuronal excitability. In parallel, a ketogenic (high-fat, low-carbohydrate) diet is a metabolic therapy that influences neuronal activity significantly, and ketogenic diets have been used successfully to treat medically-refractory epilepsy, particularly in children, for decades. To date the key neural mechanisms underlying the success of dietary therapy are unclear, hindering development of analogous pharmacological solutions. Similarly, adenosine receptor–based therapies for epilepsy and myriad other disorders remain elusive. In this review we explore the physiological regulation of adenosine as an anticonvulsant strategy and suggest a critical role for adenosine in the success of ketogenic diet therapy for epilepsy. While the current focus is on the regulation of adenosine, ketogenic metabolism and epilepsy, the therapeutic implications extend to acute and chronic neurological disorders as diverse as brain injury, inflammatory and neuropathic pain, autism and hyperdopaminergic disorders. Emerging evidence for broad clinical relevance of the metabolic regulation of adenosine will be discussed.
This review article summarises hepatitis E virus (HEV) blood donation screening strategies in effect in the European Union (EU). Since 2012, eight EU countries have implemented HEV screening. Local rates of seroprevalence, RNA incidence, and molecular epidemiology are variable and not usually directly comparable. We report a range of HEV-RNA reactivity rates from 1 in 744 donations (France) to 1 in 8,636 donations (Wales) with an overall EU rate of 1 in 3,109 donations (3.2 million donations screened). HEV genotypes 3c, 3e, and 3f are the most frequently reported subtypes. In these 8 countries, both universal (n = 5) and selective (n = 3) screening policies have been introduced utilising either individual donation (ID; n = 1) or mini-pool (MP; n = 7; MP-6, -16, -24, and -96) testing. We also describe the Irish experience of HEV screening utilising an ID-NAT-based donor screening algorithm which intercepts donations even from those with low-level viraemia; 21 of 56 donors (37.5%) had a viral load (VL) < 100 IU/mL. We performed a MP-24 experiment which may prove useful to colleagues in relation to donor screening and associated blood component transmissibility. Irish results indicate that 59% of donors with a HEV-VL < 450 IU/mL may have screened negative in a MP-24.
Anti-HBc testing is mandatory in France since 1988 and contributes to prevent occult HBV infection. Reference 1 Assal A, Barlet V, Deschaseaux M, Dupont I, Gallian P, Guitton C, Morel P, David B, De Micco P: Comparison of the analytical and operational performance of two viral nucleic acid test blood screening systems: Procleix Tigris and cobas s 201.
Question 1Investigating archive samples for HBV DNA reactive/ HBsAg non-reactive duration, we found that only about 15% of the samples investigated had a duration of less than 60 days. Meaning that in only 15% of the samples with the HBV DNA +/HBsAgresult pattern, window period could not be excluded. Therefore, majority of our NAT yield cases are OBI cases as defined by the
The presence of HCV RNA in intravenous immunoglobulin preparations which have not undergone a specific viral inactivation step is a predictor of HCV infection in recipients.
ObjectiveDue to the increased number of syphilis infections diagnosed in the UK and beyond, we reviewed our data on blood donors infected with syphilis in the UK and Ireland between 2016 and 2019.MethodsData were extracted from the surveillance database for all blood donors confirmed positive for syphilis in the UK and Ireland between 2016 and 2019, together with the total number of donations tested during that period. Data on positive cases included gender, age group, reported treatment, symptoms and confirmatory results. All cases were divided into recently acquired within 24 months and past syphilis infection. We also reviewed the information on symptoms characteristic of syphilis reported by blood donors with an untreated syphilis infection during the postdonation discussions.ResultsScreening of 8 246 600 blood donations for treponemal antibodies identified 316 blood donors with confirmed syphilis infection in the UK and Ireland between 2016 and 2019 (1.6 per 100 000 donations). 42% of them (133 of 316) were classed as a recent infection based on their donation testing results, previous donation date and clinical history provided, and they were hence considered potentially infectious. Most of these blood donors (202 of 316, 64%) had not been previously diagnosed or treated for syphilis, although 50 of them reported symptoms consistent with syphilis infection and 19 had been misdiagnosed despite seeking medical help.ConclusionsThis observational study shows that syphilis infection remains undiagnosed, especially among heterosexual men, and that infectious syphilis is often missed as a differential diagnosis even when donors have presented with genital or oral ulceration, rashes in the genital area and lymphadenopathy. Considering the recent resurgence of syphilis infections in the UK and beyond and our generally expanding sexual networks, it is important to consider syphilis in differential diagnosis even if specific risk factors have not been identified.
Background and Objectives: The aim of this study was to determine the hepatitis C virus (HCV) infection rate of recipients of different batches of anti–D immunoglobulin associated with an outbreak of HCV infection which occurred in 1977 and its relationship to the polymerase chain reaction (PCR) status of the implicated batches. This study was undertaken to determine the predictive value of HCV genome detection and quantification for subsequent infection in recipients of an HCV–contaminated anti–D immunoglobulin product for intravenous use. Materials and Methods: Sera from recipients of anti–D were tested by HCV enzyme immunoassay and if found positive were subsequently tested by recombinant immunoblot assay and HCV PCR in a national HCV anti–D screening programme set up in 1994. The HCV status of 1,342 known recipients of infectious or potentially infectious batches has been compared to the amount of HCV RNA in the anti–D batch they received so as to determine the value of PCR in the prediction of infectivity in immunoglobulin preparations. Results: It has been demonstrated that HCV–infected plasma derived from batches of anti–D showing levels of viral genome in excess of 104 genomes per millilitre led to infection of up to 60% of recipients. In contrast, batches with undetectable levels of HCV genome very rarely transmitted infection. Conclusions: The presence of HCV RNA in intravenous immunoglobulin preparations which have not undergone a specific viral inactivation step is a predictor of HCV infection in recipients.
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