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Norovirus (NoV) is a zoonotic virus that causes diarrhea in humans and animals. Outbreaks in nosocomial settings occur annually worldwide, endangering public health and causing serious social and economic burdens. The latter quarter of 2016 witnessed the emergence of the GII.P16-GII.2 recombinant norovirus throughout Asia. This genotype exhibits strong infectivity and replication characteristics, proposing its potential to initiate a pandemic. There is no vaccine against GII.P16-GII.2 recombinant norovirus, so it is necessary to design a preventive vaccine. In this study, GII.P16-GII.2 type norovirus virus-like particles (VLPs) were constructed using the baculovirus expression system and used to conduct immunizations in mice. After immunization of mice, mice were induced to produce memory T cells and specific antibodies, indicating that the VLPs induced specific cellular and humoral immune responses. Further experiments were then initiated to understand the underlying mechanisms involved in antigen presentation. Towards this, we established co-cultures between dendritic cells (DCs) or macrophages (Mø) and naïve CD4+T cells and simulated the antigen presentation process by incubation with VLPs. Thereafter, we detected changes in cell surface molecules, cytokines and related proteins. The results indicated that VLPs effectively promoted the phenotypic maturation of Mø but not DCs, as indicated by significant changes in the expression of MHC-II, costimulatory factors and related cytokines in Mø. Moreover, we found VLPs caused Mø to polarize to the M1 type and release inflammatory cytokines, thereby inducing naïve CD4+ T cells to perform Th1 immune responses. Therefore, this study reveals the mechanism of antigen presentation involving GII.P16-GII.2 recombinant norovirus VLPs, providing a theoretical basis for both understanding responses to norovirus infection as well as opportunities for vaccine development. [ABSTRACT FROM AUTHOR]

Rationale: There are limited data on mechanical discontinuation practices in Asia. Objectives: To document self-reported mechanical discontinuation practices and determine whether there is clinical equipoise regarding protocolized weaning among Asian Intensive Care specialists. Methods: A survey using a validated questionnaire, distributed using a snowball method to Asian Intensive Care specialists. Results: Of the 2,967 invited specialists from 20 territories, 2,074 (69.9%) took part. The majority of respondents (60.5%) were from China. Of the respondents, 42% worked in intensive care units (ICUs) where respiratory therapists were present; 78.9% used a spontaneous breathing trial as the initial weaning step; 44.3% frequently/always used pressure support (PS) alone, 53.4% intermittent spontaneous breathing trials with PS in between, and 19.8% synchronized intermittent mandatory ventilation with PS as a weaning mode. Of the respondents, 56.3% routinely stopped feeds before extubation, 71.5% generally followed a sedation protocol or guideline, and 61.8% worked in an ICU with a weaning protocol. Of these, 78.2% frequently always followed the protocol. A multivariate analysis involving a modified Poisson regression analysis showed that working in an ICU with a weaning protocol and frequently/always following it was positively associated with an upper-middle-income territory, a university-affiliated hospital, or in an ICU that employed respiratory therapists; and negatively with a low-income or lower-middle-income territory or a public hospital. There was no significant association with "in-house" intensivist at night, multidisciplinary ICU, closed ICU, or nurse-patient ratio. There was heterogeneity in agreement/disagreement with the statement, "evidence clearly supports protocolized weaning over nonprotocolized weaning." Conclusions: A substantial minority of Asian Intensive Care specialists do not wean patients in accordance with the best available evidence or current guidelines. There is clinical equipoise regarding the benefit of protocolized weaning. [ABSTRACT FROM AUTHOR]

Background: Despite the positive association between secondhand smoke (SHS) and cardiovascular diseases (CVD), no comprehensive assessment on the dose-response relationship between SHS and CVD has yet been reported. Therefore, a meta-analysis was conducted to update the binary association, and to elucidate the dose-response relationship of both self-reported and objectively measured SHS exposure with CVD.Methods: PubMed and Embase databases were searched for articles published up to November 12, 2019. Random-effects models were used to assess the summary odds ratios (ORs) of CVD with SHS exposure. Restricted cubic splines were used to fit the dose-response relationship.Results: Fifty-five eligible observational studies were included in this meta-analysis to investigate the association between SHS exposure and CVD. Based on the meta-analysis, the pooled OR of CVD was 1.22 (95% CI 1.17-1.28) for the self-reported SHS individuals as comparing to the non-exposed group. The result of restricted cubic splines showed a risk plateau of SHS exposure at 15 cigarettes per day (Pnon-linearity = 0.042), while other characteristics s of SHS exposure (amount, daily and cumulative duration, and cotinine) were in linear relationships with CVD (Pnon-linearity >0.05). In addition, an estimated of 6.77% (95% CI: 5.31%-8.46%) of all CVD cases in men and 7.15% (95% CI: 5.62%-8.93%) in women might be attributed to SHS exposure worldwide.Conclusions: Exposure to SHS is associated with an increased risk of CVD regardless of the modes. And thus, well-enforced smoke-free laws could possibly reduce a substantial risk of CVD caused by SHS. [ABSTRACT FROM AUTHOR]

Rationale: There are limited data on mechanical discontinuation practices in Asia. Objectives: To document self-reported mechanical discontinuation practices and determine whether there is clinical equipoise regarding protocolized weaning among Asian Intensive Care specialists. Methods: A survey using a validated questionnaire, distributed using a snowball method to Asian Intensive Care specialists. Results: Of the 2,967 invited specialists from 20 territories, 2,074 (69.9%) took part. The majority of respondents (60.5%) were from China. Of the respondents, 42% worked in intensive care units (ICUs) where respiratory therapists were present; 78.9% used a spontaneous breathing trial as the initial weaning step; 44.3% frequently/always used pressure support (PS) alone, 53.4% intermittent spontaneous breathing trials with PS in between, and 19.8% synchronized intermittent mandatory ventilation with PS as a weaning mode. Of the respondents, 56.3% routinely stopped feeds before extubation, 71.5% generally followed a sedation protocol or guideline, and 61.8% worked in an ICU with a weaning protocol. Of these, 78.2% frequently always followed the protocol. A multivariate analysis involving a modified Poisson regression analysis showed that working in an ICU with a weaning protocol and frequently/always following it was positively associated with an upper-middle-income territory, a university-affiliated hospital, or in an ICU that employed respiratory therapists; and negatively with a low-income or lower-middle-income territory or a public hospital. There was no significant association with "in-house" intensivist at night, multidisciplinary ICU, closed ICU, or nurse-patient ratio. There was heterogeneity in agreement/disagreement with the statement, "evidence clearly supports protocolized weaning over nonprotocolized weaning." Conclusions: A substantial minority of Asian Intensive Care specialists do not wean patients in accordance with the best available evidence or current guidelines. There is clinical equipoise regarding the benefit of protocolized weaning.

Importance: Little data exist on end-of-life care practices in intensive care units (ICUs) in Asia., Objective: To describe physicians' attitudes toward withholding and withdrawal of life-sustaining treatments in end-of-life care and to evaluate factors associated with observed attitudes., Design, Setting, and Participants: Self-administered structured and scenario-based survey conducted among 1465 physicians (response rate, 59.6%) who manage patients in ICUs (May-December 2012) at 466 ICUs (response rate, 59.4%) in 16 Asian countries and regions., Results: For patients with no real chance of recovering a meaningful life, 1029 respondents (70.2%) reported almost always or often withholding whereas 303 (20.7%) reported almost always or often withdrawing life-sustaining treatments; 1092 respondents (74.5%) deemed withholding and withdrawal ethically different. The majority of respondents reported that vasopressors, hemodialysis, and antibiotics could usually be withheld or withdrawn in end-of-life care, but not enteral feeding, intravenous fluids, and oral suctioning. For severe hypoxic-ischemic encephalopathy after cardiac arrest, 1201 respondents (82.0% [range between countries, 48.4%-100%]) would implement do-not-resuscitate orders, but 788 (53.8% [range, 6.1%-87.2%]) would maintain mechanical ventilation and start antibiotics and vasopressors if indicated. On multivariable analysis, refusal to implement do-not-resuscitate orders was more likely with physicians who did not value families' or surrogates' requests (adjusted odds ratio [AOR], 1.67 [95% CI, 1.16-2.40]; P = .006), who were uncomfortable discussing end-of-life care (AOR, 2.38 [95% CI, 1.62-3.51]; P < .001), who perceived greater legal risk (AOR, 1.92 [95% CI, 1.26-2.94]; P = .002), and in low- to middle-income economies (AOR, 2.73 [95% CI, 1.56-4.76]; P < .001). Nonimplementation was less likely with physicians of Protestant (AOR, 0.36 [95% CI, 0.16-0.80]; P = .01) and Catholic (AOR, 0.22 [95% CI, 0.09-0.58]; P = .002) faiths, and when out-of-pocket health care expenditure increased (AOR, 0.98 per percentage of total health care expenditure [95% CI, 0.97-0.99]; P = .02)., Conclusions and Relevance: Whereas physicians in ICUs in Asia reported that they often withheld but seldom withdrew life-sustaining treatments at the end of life, attitudes and practice varied widely across countries and regions. Multiple factors related to country or region, including economic, cultural, religious, and legal differences, as well as personal attitudes, were associated with these variations. Initiatives to improve end-of-life care in Asia must begin with a thorough understanding of these factors.

Objectives: To assess the compliance of Asian intensive care units and hospitals to the Surviving Sepsis Campaign's resuscitation and management bundles. Secondary objectives were to evaluate the impact of compliance on mortality and the organisational characteristics of hospitals that were associated with higher compliance., Design: Prospective cohort study., Setting: 150 intensive care units in 16 Asian countries., Participants: 1285 adult patients with severe sepsis admitted to these intensive care units in July 2009. The organisational characteristics of participating centres, the patients' baseline characteristics, the achievement of targets within the resuscitation and management bundles, and outcome data were recorded., Main Outcome Measure: Compliance with the Surviving Sepsis Campaign's resuscitation (six hours) and management (24 hours) bundles., Results: Hospital mortality was 44.5% (572/1285). Compliance rates for the resuscitation and management bundles were 7.6% (98/1285) and 3.5% (45/1285), respectively. On logistic regression analysis, compliance with the following bundle targets independently predicted decreased mortality: blood cultures (achieved in 803/1285; 62.5%, 95% confidence interval 59.8% to 65.1%), broad spectrum antibiotics (achieved in 821/1285; 63.9%, 61.3% to 66.5%), and central venous pressure (achieved in 345/870; 39.7%, 36.4% to 42.9%). High income countries, university hospitals, intensive care units with an accredited fellowship programme, and surgical intensive care units were more likely to be compliant with the resuscitation bundle., Conclusions: While mortality from severe sepsis is high, compliance with resuscitation and management bundles is generally poor in much of Asia. As the centres included in this study might not be fully representative, achievement rates reported might overestimate the true degree of compliance with recommended care and should be interpreted with caution. Achievement of targets for blood cultures, antibiotics, and central venous pressure was independently associated with improved survival.