154 research outputs found

    Assessment of the cross-protective capability of recombinant capsid proteins derived from pig, rat, and avian hepatitis E viruses (HEV) against challenge with a genotype 3 HEV in pigs

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    Hepatitis E virus (HEV), the causative agent of hepatitis E, is primarily transmitted via the fecal-oral route through contaminated water supplies, although many sporadic cases of hepatitis E are transmitted zoonotically via direct contact with infected animals or consumption of contaminated animal meats. Genotypes 3 and 4 HEV are zoonotic and infect humans and other animal species, whereas genotypes 1 and 2 HEV are restricted to humans. There exists a single serotype of HEV, although the cross-protective ability among the animal HEV strains is unknown. Thus, in this study we expressed and characterized N-terminal truncated ORF2 capsid antigens derived from swine, rat, and avian HEV strains and evaluated their cross-protective ability in a pig challenge model. Thirty, specific-pathogen-free, pigs were divided into 5 groups of 6 pigs each, and each group of pigs were vaccinated with 200 μg of swine HEV, rat HEV, or avian HEV ORF2 antigen or PBS buffer (2 groups) as positive and negative control groups. After a booster dose immunization at 2 weeks post-vaccination, the vaccinated animals all seroconverted to IgG anti-HEV. At 4 weeks post-vaccination, the animals were intravenously challenged with a genotype 3 mammalian HEV, and necropsied at 4 weeks post-challenge. Viremia, fecal virus shedding, and liver histological lesions were compared to assess the protective and cross-protective abilities of these antigens against HEV challenge in pigs. The results indicated that pigs vaccinated with truncated recombinant capsid antigens derived from three animal strains of HEV induced a strong IgG anti-HEV response in vaccinated pigs, but these antigens confer only partial cross-protection against a genotype 3 mammalian HEV. The results have important implications for the efficacy of current vaccines and for future vaccine development, especially against the novel zoonotic animal strains of HEV

    Diarrhoeal diseases among adult population in an agricultural community Hanam province, Vietnam, with high wastewater and excreta re-use

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    Despite the potential health risks of wastewater and excreta use as fertiliser in agriculture, it is still widespread in Vietnam. However, the importance of diarrheal risk in adults' associated with the combined exposures to both excreta and wastewater use in agriculture is largely unknown. This study was carried out to determine diarrhoeal incidence and associated risk factors among the adult population exposed to wastewater and excreta used in agriculture in Hanam province, Vietnam.; An open cohort of 867 adults, aged 16-65 years, was followed weekly for 12 months to determine the incidence of diarrhoea. A nested case-control study was used to assess the risk factors of diarrhoeal episodes. Two hundred and thirty-two pairs of cases and controls were identified and exposure information related to wastewater, human and animal excreta, personal hygiene practices, and food and water consumption was collected.; The incidence rate of reported diarrhoea was 0.28 episodes per person-years at risk. The risk factors for diarrhoeal diseases included direct contact with the Nhue River water (odds ratio [OR] = 2.4, attributable fraction [AF] 27%), local pond water (OR = 2.3, AF 14%), composting of human excreta for a duration less than 3 months (OR = 2.4, AF 51%), handling human excreta in field work (OR = 5.4, AF 7%), handling animal excreta in field work (OR = 3.3, AF 36%), lack of protective measures while working (OR = 6.9, AF 78%), never or rarely washing hands with soap (OR = 3.3, AF 51%), use of rainwater for drinking (OR = 5.4, AF 77%) and eating raw vegetables the day before (OR = 2.4, AF 12%).; Our study shows that professional exposure to wastewater and excreta during agricultural activities are significantly contributing to the risk of diarrhoea in adults. The highest attributable fractions were obtained for direct contact with Nhue River and local ponds, handling practices of human and animal excreta as fertilisers, lack of protective measures while working and poor personal hygiene practices, and unsafe food and water consumption were associated with the risk of diarrhoeal episodes in adults. Improve personal hygiene practices and use of relevant treated wastewater and excreta as the public health measures to reduce these exposures will be most effective and are urgently warranted

    A chimeric nuclease substitutes a phage CRISPR-Cas system to provide sequence-specific immunity against subviral parasites

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    Mobile genetic elements, elements that can move horizontally between genomes, have profound effects on their host's fitness. The phage-inducible chromosomal island-like element (PLE) is a mobile element that integrates into the chromosome of Vibrio cholerae and parasitizes the bacteriophage ICP1 to move between cells. This parasitism by PLE is such that it abolishes the production of ICP1 progeny and provides a defensive boon to the host cell population. In response to the severe parasitism imposed by PLE, ICP1 has acquired an adaptive CRISPR-Cas system that targets the PLE genome during infection. However, ICP1 isolates that naturally lack CRISPR-Cas are still able to overcome certain PLE variants, and the mechanism of this immunity against PLE has thus far remained unknown. Here, we show that ICP1 isolates that lack CRISPR-Cas encode an endonuclease in the same locus, and that the endonuclease provides ICP1 with immunity to a subset of PLEs. Further analysis shows that this endonuclease is of chimeric origin, incorporating a DNA-binding domain that is highly similar to some PLE replication origin-binding proteins. This similarity allows the endonuclease to bind and cleave PLE origins of replication. The endonuclease appears to exert considerable selective pressure on PLEs and may drive PLE replication module swapping and origin restructuring as mechanisms of escape. This work demonstrates that new genome defense systems can arise through domain shuffling and provides a greater understanding of the evolutionary forces driving genome modularity and temporal succession in mobile elements

    A phage weaponizes a satellite recombinase to subvert viral restriction

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    Bacteria can acquire mobile genetic elements (MGEs) to combat infection by viruses (phages). Satellite viruses, including the PLEs (phage-inducible chromosomal island-like elements) in epidemic Vibrio cholerae, are MGEs that restrict phage replication to the benefit of their host bacterium. PLEs parasitize the lytic phage ICP1, unleashing multiple mechanisms to restrict phage replication and promote their own spread. In the arms race against PLE, ICP1 uses nucleases, including CRISPR-Cas, to destroy PLE’s genome during infection. However, through an unknown CRISPR-independent mechanism, specific ICP1 isolates subvert restriction by PLE. Here, we discover ICP1-encoded Adi that counteracts PLE by exploiting the PLE’s large serine recombinase (LSR), which normally mobilizes PLE in response to ICP1 infection. Unlike previously characterized ICP1-encoded anti-PLE mechanisms, Adi is not a nuclease itself but instead appears to modulate the activity of the LSR to promote destructive nuclease activity at the LSR’s specific attachment site, attP. The PLE LSR, its catalytic activity, and attP are additionally sufficient to sensitize a PLE encoding a resistant variant of the recombination module to Adi activity. This work highlights a unique type of adaptation arising from inter-genome conflicts, in which the intended activity of a protein can be weaponized to overcome the antagonizing genome

    Nutritional status, dietary quality and eating disturbance issues among people with dementia in Vietnam: evidence of a cross-sectional study

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    \ua9 The Author(s) 2024.Background: Due to cognitive impairments, people with dementia (PWD) often have difficulties in eating and drinking. This study aimed to assess the nutritional status, dietary quality and eating disturbance issues among PWD in Vietnam. Methods: We conducted a cross-sectional study at the Vietnamese National Geriatric Hospital from April to December 2022. We used Mini-Mental State Exam (MMSE) to classify the severity levels of dementia. Mini Nutritional Assessment (MNA), 24-hour recall, eating disturbance questionnaires, and anthropometric indicators were used to evaluate the nutritional status, dietary quality, and eating disorders of study subjects. Results: Overall, among 63 study participants, 74.6 per cent of PWD were at risk of or having malnutrition. By dementia classification according to MMSE scale, people with moderate and severe dementia accounted for 53.3 per cent of those who met the recommended energy levels, compared to 42.4 per cent of people with mild dementia and normal people. In the above two groups, around three per cent of participants reached the recommended amount of fibre. Calcium (50–70%), vitamin A (80–90%), and D (90%) were found to be the most severe deficiency forms of minerals and vitamins in both male and female participants. The majority of participants (90.5%) had at least one form of eating disorders with the most frequent issue being appetite changes (76.2%) and swallowing issues (50.8%). Conclusions: PWD in our sample frequently experienced malnutrition, a lack of essential nutrients, difficulties swallowing, changes in eating habits and appetite. It is neccesary to early screen and assess nutritional status and swallowing disturbance in PWD, and instruct their caregivers to prepare nutritious meals for them

    A telepresence wheelchair with 360-degree vision using WebRTC

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    © 2020 The Author(s). This paper presents an innovative approach to develop an advanced 360-degree vision telepresence wheelchair for healthcare applications. The study aims at improving a wide field of view surrounding the wheelchair to provide safe wheelchair navigation and efficient assistance for wheelchair users. A dual-fisheye camera is mounted in front of the wheelchair to capture images which can be then streamed over the Internet. Aweb real-time communication (WebRTC) protocol was implemented to provide efficient video and data streaming. An estimation model based on artificial neural networks was developed to evaluate the quality of experience (QoE) of video streaming. Experimental results confirmed that the proposed telepresence wheelchair system was able to stream a 360-degree video surrounding the wheelchair smoothly in real-time. The average streaming rate of the entire 360-degree video was 25.83 frames per second (fps), and the average peak signal to noise ratio (PSNR) was 29.06 dB. Simulation results of the proposed QoE estimation scheme provided a prediction accuracy of 94%. Furthermore, the results showed that the designed system could be controlled remotely via the wireless Internet to follow the desired path with high accuracy. The overall results demonstrate the effectiveness of our proposed approach for the 360-degree vision telepresence wheelchair for assistive technology applications

    User involvement in a Cochrane systematic review: using structured methods to enhance the clinical relevance, usefulness and usability of a systematic review update

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    Background: This paper describes the structured methods used to involve patients, carers and health professionals in an update of a Cochrane systematic review relating to physiotherapy after stroke and explores the perceived impact of involvement.Methods: We sought funding and ethical approval for our user involvement. We recruited a stakeholder group comprising stroke survivors, carers, physiotherapists and educators and held three pre-planned meetings during the course of updating a Cochrane systematic review. Within these meetings, we used formal group consensus methods, based on nominal group techniques, to reach consensus decisions on key issues relating to the structure and methods of the review.Results: The stakeholder group comprised 13 people, including stroke survivors, carers and physiotherapists with a range of different experience, and either 12 or 13 participated in each meeting. At meeting 1, there was consensus that methods of categorising interventions that were used in the original Cochrane review were no longer appropriate or clinically relevant (11/13 participants disagreed or strongly disagreed with previous categories) and that international trials (which had not fitted into the original method of categorisation) ought to be included within the review (12/12 participants agreed or strongly agreed these should be included). At meeting 2, the group members reached consensus over 27 clearly defined treatment components, which were to be used to categorise interventions within the review (12/12 agreed or strongly agreed), and at meeting 3, they agreed on the key messages emerging from the completed review. All participants strongly agreed that the views of the group impacted on the review update, that the review benefited from the involvement of the stakeholder group, and that they believed other Cochrane reviews would benefit from the involvement of similar stakeholder groups.Conclusions: We involved a stakeholder group in the update of a Cochrane systematic review, using clearly described structured methods to reach consensus decisions. The involvement of stakeholders impacted substantially on the review, with the inclusion of international studies, and changes to classification of treatments, comparisons and subgroup comparisons explored within the meta-analysis. We argue that the structured approach which we adopted has implications for other systematic reviews.</p

    Human Neonatal Hepatocyte Transplantation Induces Long-Term Rescue of Unconjugated Hyperbilirubinemia in the Gunn Rat

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    International audienceCrigler-Najjar type 1 disease is a rare inherited metabolic disease characterized by high levels of unconjugated bilirubin due to the complete absence of hepatic uridine diphosphoglucuronate-glucuronosyltransferase activity. Hepatocyte transplanta-tion (HT) has been proposed as an alternative treatment for Crigler-Najjar syndrome, but it is still limited by the quality and the low engraftment and repopulation ability of the cells used. Because of their attachment capability and expression of adhesion molecules as well as the higher proportion of hepatic progenitor cells, neonatal hepatocytes may have an advantage over adult cells. Adult or neonatal hepatocytes were transplanted into Gunn rats, a model for Crigler-Najjar disease. Engraftment and repopulation were studied and compared by immunofluorescence (IF). Additionally, the serum bilirubin levels , the presence of bilirubin conjugates in rat serum, and the expression of uridine diphosphate glucuronosyltransferase 1 family polypeptide A1 (UGT1A1) in rat liver samples were also analyzed. Here we show that neonatal HT results in long-term correction in Gunn rats. In comparison with adult cells, neonatal cells showed better engraftment and repopulation capability 3 days and 6 months after transplantation, respectively. Bilirubinemia decreased in the transplanted animals during the whole experimental follow-up (6 months). Bilirubin conjugates were also present in the serum of the transplanted Additional Supporting Information may be found in the online version of this article
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