Molecular characterization of enterovirus 71 sibling strains for thermal adaption in Vero cells with adaptive laboratory evolution

Enterovirus 71 is the main pathogen that causes severe and fatal hand-foot-mouth-disease (HFMD) cases. As the enterovirus virus mutation has implications for pathogenesis, vaccine development, antiviral therapy, and epidemiological disease management of the virus. In this study, we investigated the variations of enterovirus 71 in thermal adaption, using the method of adaptive laboratory evolution. The sibling virus strains were isolated from a 2-year-old severe case of HFMD (#100) and her symptomless close contact (#101). Both strains were cultured in Vero cells by serial passage of 36 generations at the temperatures of 28.0 °C, 33.0 °C and 39.5 °C to construct adaptive lineages. According to the comparative analysis of phenotypes between adapted strains and parental strains, differences in growth rate were observed in the sibling lineages and a larger plaque was found mainly in the hot adapted strains for lineage #101. Two sets of adaptive strains from six time points (parental, 12th 17th, 31st, 35th passage and endpoint) were sequenced and analyzed by both Sanger sequencing and Next Generation Sequencing. Several variations in most coding genes and one reverse mutation in 5′UTR was observed, along with the identity of 99.8% for complete genome for both lineages. Notably, thermal specific non-synonymous mutations were found in the gene of VP1\VP3\3A\2C\3C. Moreover, the concurrent mutations A292G, A434G and A355C/T of sibling lineages in VP1 showed quantificational trace with distinguishing patterns for different temperatures, which were suspected to be the thermo-sensitive mutation hotspots. These results highlight the possible rules of thermal adaption in enterovirus 71, produce a novel picture of genome evolution of the virus, and shed light on viral variation and evolution.     

Real-world cost-effectiveness of drug-eluting stents vs. bare-metal stents for coronary heart disease—A five-year follow-up study

Objective

To evaluate the cost-effectiveness of using drugeluting stents (DES) compared to bare-metal stents (BMS) for coronary heart disease (CHD).

Assessing healthcare digitalisation in Ghana: A critical realist's approach

BackgroundThe emergence of digital technologies within the health sector has presented opportunities for improving medical care while strengthening health systems across the globe. Despite this promise, the extent of digitalisation, especially in developing countries, somewhat remains undetermined. Such knowledge is needed to learn and shape future advances in the sector. The purpose of this study, therefore, is to explore the generative mechanisms of digitalisation in the Ghanaian health sector, in order to understand and assess the extent of digitalisation, based on the digitalisation outcomes of the respective generative mechanisms.MethodsUnderpinned by the critical realism philosophy, a single case study approach was adopted to explore the generative mechanisms of digitalisation in the Ghanaian health sector, and how the varying degrees of digitalisation are interpreted and explained in the empirical world.ResultsThe study found five generative mechanisms of digitalisation in the Ghanaian health sector. These were Standardisation, Convergence and Connectivity, Storage Systems, Financial Transparency, and Data Security. Full activation of these mechanisms revealed that the first three generative mechanisms achieved high levels of digitalisation based on the extent of organisational transformations observed after the digitalisation process, as compared to the last two generative mechanisms which were rated as average.DiscussionThis study concludes that the extent of digitalisation in Ghana's health sector is more of reality than mere perception. The demonstration of how critical realism can be used to unearth insights into the extent of healthcare digitalisation in a developing country context spells the contribution of this paper.     

Hepatitis C infection and psychiatric burden in two imprisoned cohorts: Young offenders and opioid-maintained prisoners

Prisoners constitute a considerable gap in the hepatitis C virus (HCV) tested population. The present study examined HCV prevalence in imprisoned opioid-maintained patients (OMT-P) and adolescents and young adults (AYA, 14–26 years). In addition, HCV testing and treatment provision, knowledge of HCV status and psychiatric comorbidity were assessed. Data collection took place in six Austrian prisons. Participants were N = 133 for OMT-P (78% male, mean age 35.7 years) and N = 71 for AYA (100% male, mean age 19.8 years). Analysis of HCV serology was conducted. Psychiatric comorbidity and addiction severity were assessed applying standardized questionnaires and interviews. Antibodies were detected in 74.4% of OMT-P, and in 45.0% HCV infection was confirmed. Only one AYA was infected with HCV. None of the participants was receiving treatment for HCV. Eleven percent of OMT-P (50.7% of AYA) did not know their HCV status, and 14.3% of OMT-P (36.6% of AYA) had not been tested in prison. Among OMT-P, lifetime IDU [OR = 330.33, CI = 25.91–4433.20] and age at first IDU [OR = 0.90, CI = 0.82–0.98] significantly predicted HCV status. In both samples, a high prevalence of affective disorders was observed. Despite the high prevalence of HCV among opioid-dependent detainees, the unique opportunities for comprehensive testing and treatment of HCV are substantially underutilized. This is in stark contrast to the UN Basic Principles for the Treatment of Prisoners.     

Nicotine in thirdhand smoke residue predicts relapse from smoking cessation: A pilot study

IntroductionThirdhand smoke (THS) residue lingers for months in homes of former smokers and may play a role in relapse after smoking cessation. This study examined the association between THS pollution as measured by the level of nicotine in house dust and continued abstinence from smoking.MethodsParticipants were 65 cigarette smokers who reported they were enrolled in any type of smoking cessation program, had set a specific date to quit, and had biochemical verification of continuous abstinence at 1-week (W1), 1-month (M1), 3-months (M3), or 6-months (M6) after their quit date. House dust samples collected at baseline before quitting were analyzed for nicotine concentration (μg/g) and nicotine loading (μg/m²) using liquid chromatography-tandem mass spectrometry (LC-MS/MS).ResultsControlling for age, gender, overall and indoor smoking rates, and years lived in their home, dust nicotine concentration and loading predicted abstinence at W1, M1, M3, and M6. A 10-fold increase in dust nicotine loading and concentration were associated with approximately 50% lower odds of remaining abstinent.ConclusionsFindings suggest nicotine in house dust may play a role in facilitating relapse after smoking cessation. Additional research is warranted to investigate the causal role of THS residue in homes of former smokers on cravings and continued abstinence.     

Thymoquinone alleviates thioacetamide-induced hepatic fibrosis and inflammation by activating LKB1–AMPK signaling pathway in mice

The current study was conducted to investigate the anti-fibrotic effect and its possible underlying mechanisms of thymoquinone (TQ) against hepatic fibrosis in vivo. TQ is the major active compound derived from the medicinal Nigella sativa. Liver fibrosis was induced in male Kunming mice by intraperitoneal injections of thioacetamide (TAA, 200 mg/kg). Mice were treated concurrently with TAA alone or TAA plus TQ (20 mg/kg or 40 mg/kg) given daily by oral gavage. Our data demonstrated that TQ treatment obviously reversed liver tissue damage compared with TAA alone group, characterized by less inflammatory infiltration and accumulation of extracellular matrix (ECM) proteins. TQ significantly attenuated TAA-induced liver fibrosis, accompanied by reduced protein and mRNA expression of α-smooth muscle actin (α-SMA), collagen-І and tissue inhibitor of metalloproteinase-1 (TIMP-1). TQ downregulated the expression of toll-like receptor 4 (TLR4) and remarkably decreased proinflammatory cytokine levels as well. TQ also significantly inhibited phosphatidylinositol 3-kinase (PI3K) phosphorylation. Furthermore, TQ enhanced the phosphorylation adenosine monophosphate-activated protein kinase (AMPK) and liver kinase B (LKB)-1. In conclusion, TQ may reduce ECM accumulation, and it may be at least regulated by phosphorylation of AMPK signaling pathways, suggesting that TQ may be a potential candidate for the therapy of hepatic fibrosis.     

Effects of Virtual Reality Rehabilitation Training on Cognitive Function and Activities of Daily Living of Patients With Poststroke Cognitive Impairment: A Systematic Review and Meta-Analysis

ObjectiveTo determine the effects of virtual reality (VR) rehabilitation training on the cognitive function and activities of daily living (ADL) of patients with poststroke cognitive impairment (PSCI).Data SourcesFour Chinese databases and 6 English databases were systematically searched for studies published until August 31, 2021, by using Medical Subject Headings of the National Library of Medicine terms such as virtual reality, cognition disorders, cognitive dysfunction, and stroke and free terms such as virtual environment, VR, cognition impairment, cerebrovascular accident, and PSCI.Study SelectionRandomized controlled trials treating PSCI with VR training were included. The control groups received conventional treatments such as conventional rehabilitation training and drug therapy; the experimental groups received VR rehabilitation training. The outcome measures were cognitive function and ADL.Data ExtractionTwo researchers independently extracted key information from eligible studies. The methodological quality of the studies was evaluated using the Cochrane Handbook for Systematic Reviews of Interventions v5.1.0. Meta-analysis was performed using RevMan v5.4. We followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020 guidelines.Data SynthesisTwenty-one studies (1149 participants) were included. Meta-analyses found that compared with the control group, VR rehabilitation training increased Mini-Mental State Examination, Montreal Cognitive Assessment, Loewenstein Occupational Therapy Cognitive Assessment, Rivermead Behavioral Memory Test Second Edition, Barthel Index, Modified Barthel Index, and FIM scores; event-related potential 300 (P300) amplitude; and the N-acetylaspartate/creatinine (Cr) ratio on proton magnetic resonance spectroscopy (¹H-MRS) and reduced P300 latency; Trail Making Test scores; and the choline-containing compounds/Cr ratio on ¹H-MRS (all P<.05). These results indicated that VR training improved cognitive function and ADL in PSCI.ConclusionsVR rehabilitation training promotes the rehabilitation of cognitive function and recovery of ADL in patients with PSCI and may be a good complementary approach to conventional cognitive interventions.