59 research outputs found

    Immune interference in effectiveness of influenza and COVID-19 vaccination

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    Vaccines are known to function as the most effective interventional therapeutics for controlling infectious diseases, including polio, smallpox, rabies, tuberculosis, influenza and SARS-CoV-2. Smallpox has been eliminated completely and polio is almost extinct because of vaccines. Rabies vaccines and Bacille Calmette-Guérin (BCG) vaccines could effectively protect humans against respective infections. However, both influenza vaccines and COVID-19 vaccines are unable to eliminate these two infectious diseases of their highly variable antigenic sites in viral proteins. Vaccine effectiveness (VE) could be negatively influenced (i.e., interfered with) by immune imprinting of previous infections or vaccinations, and repeated vaccinations could interfere with VE against infections due to mismatch between vaccine strains and endemic viral strains. Moreover, VE could also be interfered with when more than one kind of vaccine is administrated concomitantly (i.e., co-administrated), suggesting that the VE could be modulated by the vaccine-induced immunity. In this review, we revisit the evidence that support the interfered VE result from immune imprinting or repeated vaccinations in influenza and COVID-19 vaccine, and the interference in co-administration of these two types of vaccines is also discussed. Regarding the development of next-generation COVID-19 vaccines, the researchers should focus on the induction of cross-reactive T-cell responses and naive B-cell responses to overcome negative effects from the immune system itself. The strategy of co-administrating influenza and COVID-19 vaccine needs to be considered more carefully and more clinical data is needed to verify this strategy to be safe and immunogenic

    Abnormal Liver Function Tests Were Associated With Adverse Clinical Outcomes: An Observational Cohort Study of 2,912 Patients With COVID-19

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    Background and Aim: The impact of liver function test (LFTs) abnormality on adverse clinical outcomes in coronavirus disease 2019 (COVID-19) patients remains controversial. The aim of this study was to assess the impact of abnormal LFTs on clinical outcomes in a large cohort of hospitalized patients with COVID-19.Methods: We retrospectively collected data on 2,912 consecutive patients with COVID-19 who were admitted to a makeshift hospital in China between 5 February and 23 March 2020. The association between LFTs abnormalities (baseline and peak values) and clinical outcomes was measured by using Cox regression models.Results: On admission 1,414 patients (48.6%) had abnormal LFTs, with alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (TBIL), alkaline phosphatase (ALP), and gamma-glutamyltransferase (GGT) elevation in 662 (22.7%), 221 (7.6%), 52 (1.8%), 135 (4.6%), and 536 (18.5%) patients, respectively, and hypoalbuminemia in 737 (25.3%) patients. During a median 13 (IQR: 8–19) days of hospitalization, 61 patients (2.1%) died, 106 patients (3.6%) admitted to intensive care unit (ICU), and 75 patients (2.6%) required mechanical ventilation. After adjustment for confounders, baseline abnormal LFTs were independently associated with increased risks of mortality (adjusted HR 3.66, 95%CI 1.64–8.19, p = 0.002), ICU admission (adjusted HR 3.12 95%CI 1.86–5.23, p < 0.001), and mechanical ventilation (adjusted HR 3.00, 95%CI 1.63–5.52, p < 0.001), which was homogeneous across the severity of COVID-19 infection. Among the parameters of LTFs, the associations with the outcomes were more pronounced for AST and albumin abnormality. In contrast, ALT elevation was not significantly associated with those outcomes. Similar results were observed for peak values of LFTs during hospitalization.Conclusions: Abnormality of AST, albumin, TBIL, ALP, and GGT but not ALT were independently associated with adverse outcomes

    Multiplatform genome-wide identification and modeling of functional human estrogen receptor binding sites

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    BACKGROUND: Transcription factor binding sites (TFBS) impart specificity to cellular transcriptional responses and have largely been defined by consensus motifs derived from a handful of validated sites. The low specificity of the computational predictions of TFBSs has been attributed to ubiquity of the motifs and the relaxed sequence requirements for binding. We posited that the inadequacy is due to limited input of empirically verified sites, and demonstrated a multiplatform approach to constructing a robust model. RESULTS: Using the TFBS for the estrogen receptor (ER)α (estrogen response element [ERE]) as a model system, we extracted EREs from multiple molecular and genomic platforms whose binding to ERα has been experimentally confirmed or rejected. In silico analyses revealed significant sequence information flanking the standard binding consensus, discriminating ERE-like sequences that bind ERα from those that are nonbinders. We extended the ERE consensus by three bases, bearing a terminal G at the third position 3' and an initiator C at the third position 5', which were further validated using surface plasmon resonance spectroscopy. Our functional human ERE prediction algorithm (h-ERE) outperformed existing predictive algorithms and produced fewer than 5% false negatives upon experimental validation. CONCLUSION: Building upon a larger experimentally validated ERE set, the h-ERE algorithm is able to demarcate better the universe of ERE-like sequences that are potential ER binders. Only 14% of the predicted optimal binding sites were utilized under the experimental conditions employed, pointing to other selective criteria not related to EREs. Other factors, in addition to primary nucleotide sequence, will ultimately determine binding site selection

    Finishing the euchromatic sequence of the human genome

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    The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

    Prevalence, associated factors and outcomes of pressure injuries in adult intensive care unit patients: the DecubICUs study

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    Funder: European Society of Intensive Care Medicine; doi: http://dx.doi.org/10.13039/501100013347Funder: Flemish Society for Critical Care NursesAbstract: Purpose: Intensive care unit (ICU) patients are particularly susceptible to developing pressure injuries. Epidemiologic data is however unavailable. We aimed to provide an international picture of the extent of pressure injuries and factors associated with ICU-acquired pressure injuries in adult ICU patients. Methods: International 1-day point-prevalence study; follow-up for outcome assessment until hospital discharge (maximum 12 weeks). Factors associated with ICU-acquired pressure injury and hospital mortality were assessed by generalised linear mixed-effects regression analysis. Results: Data from 13,254 patients in 1117 ICUs (90 countries) revealed 6747 pressure injuries; 3997 (59.2%) were ICU-acquired. Overall prevalence was 26.6% (95% confidence interval [CI] 25.9–27.3). ICU-acquired prevalence was 16.2% (95% CI 15.6–16.8). Sacrum (37%) and heels (19.5%) were most affected. Factors independently associated with ICU-acquired pressure injuries were older age, male sex, being underweight, emergency surgery, higher Simplified Acute Physiology Score II, Braden score 3 days, comorbidities (chronic obstructive pulmonary disease, immunodeficiency), organ support (renal replacement, mechanical ventilation on ICU admission), and being in a low or lower-middle income-economy. Gradually increasing associations with mortality were identified for increasing severity of pressure injury: stage I (odds ratio [OR] 1.5; 95% CI 1.2–1.8), stage II (OR 1.6; 95% CI 1.4–1.9), and stage III or worse (OR 2.8; 95% CI 2.3–3.3). Conclusion: Pressure injuries are common in adult ICU patients. ICU-acquired pressure injuries are associated with mainly intrinsic factors and mortality. Optimal care standards, increased awareness, appropriate resource allocation, and further research into optimal prevention are pivotal to tackle this important patient safety threat

    Correlation Analysis of Mineral Element Content and Sensory Quality of National Geographical Sign Product--Olecranon Peaches in Lianping

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    Microwave digestion-inductively coupled plasma astigmatism (ICP-AES) was used to analyze the contents of mineral elements (including K, P, Mg, Ca, Na, Fe, Cu, Mn, B, Zn, Se, Li) in 54 Olecranon Peaches collected from Shangping town, Lianping County. The obtained data was analyzed by Correlation analysis (CA), combined with fruit reducing sugar (RS%), sugar-acid ratio (S/A) and sensory scores. The results showed that in the tested samples, it had a significant positive correlation between S/A sugar-acid ratio and sensory evaluation. S/A was negatively correlated with P contents. The P contents were positively correlated with the K, Mg contents. The Mg contents were positively correlated with the K, Na contents. The Na contents were positively correlated with the Mn contents. The contents of Mn were positively correlated with RS% ratios of reducing sugar

    Calligraphy-based rehabilitation exercise for improving the upper limb function of stroke patients: protocol for an evaluator-blinded randomised controlled trial

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    Introduction A common complication of stroke is upper limb dysfunction. Chinese calligraphy handwriting (CCH) is an aesthetical exercise developed from the traditional way of writing in China and holds potential to become a rehabilitation method to improve upper limb functions in patients with stroke. This study aims to design a randomised controlled trial to assess the effect of a customised CCH-based exercise for poststroke rehabilitation of upper limb dysfunction. Methods and analysis A single-blinded randomised controlled trial will be conducted on 60 stroke patients. The patients will be randomly allocated into three groups: (1) conventional occupational therapy (COT) group, (2) COT+CCH group, (3) COT+Graded Repetitive Arm Supplementary Program (GRASP) group. For the COT group, patients will receive COT treatment of 1 hour/day. For the COT+CCH group, patients will receive 30 mins COT treatment and 30 mins CCH training. For the COT+GRASP group, patients will receive 30 mins COT treatment and 30 mins GRASP training. All the interventions will be performed 5 days per week for a total of 3 weeks. The upper limb functions will be assessed before and after the interventions using a series of rating scales. Ethics and dissemination This study has been approved by the Research Ethics Committees of the Second Rehabilitation Hospital of Shanghai (study ID: 2020-32-01) and the Shanghai University of Sport (study ID: 102772021RT043). Results will be directly disseminated to the patients at the end of the study and to the public via publications in peer-reviewed journals and presentations in conferences. Trial registration number ChiCTR 2100043036; Chinese Clinical Trials Registry.ISSN:2044-605
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