Hepatitis E virus (HEV) in Scotland: evidence of recent increase in viral circulation in humans.

BackgroundPrevious studies showed low levels of circulating hepatitis E virus (HEV) in Scotland. We aimed to reassess current Scottish HEV epidemiology. Methods: Blood donor samples from five Scottish blood centres, the minipools for routine HEV screening and liver transplant recipients were tested for HEV antibodies and RNA to determine seroprevalence and viraemia. Blood donor data were compared with results from previous studies covering 2004-08. Notified laboratory-confirmed hepatitis E cases (2009-16) were extracted from national surveillance data. Viraemic samples from blood donors (2016) and chronic hepatitis E transplant patients (2014-16) were sequenced. Results: Anti-HEV IgG seroprevalence varied geographically and was highest in Edinburgh where it increased from 4.5% in 2004-08) to 9.3% in 2014-15 (p = 0.001). It was most marked in donors < 35 years. HEV RNA was found in 1:2,481 donors, compared with 1:14,520 in 2011. Notified laboratory-confirmed cases increased by a factor of 15 between 2011 and 2016, from 13 to 206. In 2011-13, 1 of 329 transplant recipients tested positive for acute HEV, compared with six cases of chronic infection during 2014-16. Of 10 sequenced viraemic donors eight and all six patients were infected with genotype 3 clade 1 virus, common in European pigs. Conclusions: The seroprevalence, number of viraemic donors and numbers of notified laboratory-confirmed cases of HEV in Scotland have all recently increased. The causes of this change are unknown, but need further investigation. Clinicians in Scotland, particularly those caring for immunocompromised patients, should have a low threshold for testing for HEV.

'I didn't feel like I was a doctor': a qualitative interview study exploring the experiences and representations of healthcare professionals' capacity to deliver compassionate care and to practice self-care during the Covid-19 pandemic.

OBJECTIVE: The increased demand on healthcare professionals (HCPs) during the Coronavirus Disease (Covid-19) pandemic reduces opportunities for HCPs to deliver compassionate care to patients and to maintain self-care. This study explored how HCPs understand and experience compassionate working practices during the Covid-19 pandemic to better support HCPs' wellbeing and to sustain quality of care. DESIGN: All nineteen participants worked as an HCP during the Covid-19 pandemic, resided in the United Kingdom (UK) and took part in individual semi-structured interviews. MAIN OUTCOME MEASURES: Using a thematic analysis approach, we developed three themes: (a) The art of compassionate care: Feeling and action, (b) The impact of Covid-19 on compassionate care and (c) Suffering during Covid-19: The importance of self-compassion and self-care. RESULTS: Overall, the analysis illustrated the strong and negative impact that Covid-19 had on the ability to deliver compassionate care, resulting in moral injury and psychological and behavioural difficulties for HCPs, particularly in terms of self-care. CONCLUSIONS: This research demonstrates an imperative need for organisations to better support HCPs' health and wellbeing, through a self-care system that promotes self-compassionate and self-care practices.

Expression Profiles of Exosomal MicroRNAs from HEV- and HCV-Infected Blood Donors and Patients: A Pilot Study.

Exosomes seem to play an important role in hepatits C virus (HCV) and hepatitis E virus (HEV) infection by shielding their cargo from the host immune responses, with microRNAs being key exosomal components. Little is known about their involvement in a mixed HCV/HEV infection or at the early stages of infection, such as in asymptomatic blood donors (BDs). To obtain preliminary data, we have compared the exosomal microRNA expression profiles in four each of HCV RNA-positive, HEV RNA-positive and negative blood donors and four patients, one of whom was a rare patient with HCV/HEV co-infection. Exosomes were purified from sera by a combination of a precipitation and density gradient centrifugation and exosomal microRNA was analysed using Taqman array cards. Out of 33 deregulated miRNAs, miR-885-5p and miR-365 were upregulated in HCV BDs, miR-627-5p was downregulated in HCV BD and miR-221 was downregulated in HCV patients and BDs. In HEV infection, miR-526b appeared specifically downregulated. Six miRNAs (miR-628-3p, miR-194, miR-151-3p, miR-512-3p, miR-335 and miR-590) indicated a potential involvement in both infections. First time preliminary data on pre- and post-antiviral treatment exosomal microRNA profiles of the HEV/HCV co-infected patient revealed a pool of 77 upregulated and 43 downregulated miRNAs to be further investigated for their potential roles in these viral infections.

Thiamine phosphokinase deficiency and mutation in TPK1 presenting as biotin responsive basal ganglia disease.

The product of thiamine phosphokinase is the cofactor for many enzymes, including the dehydrogenases of pyruvate, 2-ketoglutarate and branched chain ketoacids. Its deficiency has recently been described in a small number of patients, some of whom had a Leigh syndrome phenotype. The patient who also had a Leigh phenotype was initially found to have a low concentration of biotin in plasma and massive urinary excretion of biotin. Despite treatment with biotin and thiamine, her disease was progressive. Mutations c.311delG and c.426G > C were found in the TPK1 gene.

HIV-related risk behaviors, perceptions of risk, HIV testing, and exposure to prevention messages and methods among urban American Indians and Alaska Natives.

The goal of this study was to describe HIV risk behaviors, perceptions, testing, and prevention exposure among urban American Indians and Alaska Natives (AI/AN). Interviewers administered a questionnaire to participants recruited through anonymous peer-referral sampling. Chi-square tests and multiple logistic regression were used to compare HIV testing by perception of risk and risk behavior status. Of 218 respondents with seronegative or unknown HIV status, 156 (72%, 95% confidence interval [CI]: 66-78%) reported some HIV risk behavior: 57 (26%, 95% CI: 20-32%) high-risk behavior, and 99 (45%, 95% CI: 39-52%), potentially high-risk. Among respondents reporting high-risk behavior, 44% rated themselves at no or low risk for HIV infection. Overall, 180 respondents (83%, 95% CI: 78-88%) had ever received an HIV test, 79 (36%, 95% CI: 31-57%) in the past year. HIV risk behaviors and perception of risk were independently associated with recent HIV testing after adjustment for gender, income, and homelessness (odds ratio [OR] = 3.6; 95% CI: 1.5-9.0 for high-risk behavior vs. no reported risk behavior, and OR: 3.2; 95% CI: 1.3-7.6, for high vs. no perceived risk). Addressing inaccurate perception of risk may be a key to improving uptake of HIV testing among high-risk urban AI/AN.

The role of methionine in ethylmalonic encephalopathy with petechiae.

BACKGROUND: Among patients with ethylmalonic aciduria, a subgroup with encephalopathy, petechial skin lesions, and often death in infancy is distinct from those with short-chain acyl-coenzyme A dehydrogenase deficiency or multiple acyl-coenzyme A dehydrogenase deficiency. The nature of the molecular defect in this subgroup is unknown, and the source of the ethylmalonic acid has been unclear. OBJECTIVE: To determine whether the administration of candidate amino acids increased the excretion of ethylmalonic acid. DESIGN: Examination of patterns of organic acids excreted in the urine before and following loading doses of isoleucine and methionine. SETTING: General clinical research center. PATIENT: An infant with ethylmalonic aciduria, global developmental delay, acrocyanosis, and intermittent showers of petechiae. MAIN OUTCOME MEASURE: Excretion of ethylmalonic acid in the urine. RESULTS: Loading with methionine increased the excretion of ethylmalonic acid, whereas loading with isoleucine did not. Restriction of the dietary intake of methionine decreased ethylmalonic acid excretion. CONCLUSION: In ethylmalonic acid encephalopathy with petechiae, methionine is a precursor of ethylmalonic acid.

Chronic treatment of mitochondrial disease patients with dichloroacetate.

Clinical features are reported for 37 patients with various mitochondrial disorders, treated with sodium dichloroacetate (DCA) for 3 weeks to 7 years (mean 3.25 years) at 11-50 mg/kg/day (34.6+/-13.1) in an open-label format. DCA pharmacokinetics showed half-times approximately 86 min for the first intravenous dose of 50 mg/kg, 3.2 h for a subsequent intravenous dose 4-6 h later, and 11 h after continued oral dosing of 12.5-25 mg/kg twice daily. Basal blood and CSF lactate (mean values at entry 29.6 and 46.8 mg/dL, respectively) decreased at 3 months (to 18.1 and 34.2, respectively) and 12 months (to 17.7 and 33.1, respectively). There was some attenuation of the blood lactate response to oral fructose but not glucose, although the baseline lactate was lower with DCA. A standardized neurologic inventory showed stabilization or improvement over one year. The subjective impression of overall disease course was worsening in 21.6%, improvement in 48.6%, and no discernable effect in 29.7%. Among 8 patients who had 17 stroke-like events in 0.25-5 years prior to study entry, there were a total of 2 events over 3-6 years of treatment. In two cases institution of DCA resulted in dramatic relief of severe headaches which had been refractory to narcotics. Given variability of symptoms and limited understanding of natural history of mitochondrial disease, it is difficult to determine the efficacy of DCA in this open-label study, but there did appear to be some cases in which there were at least temporary benefits.