Toll-like receptors (TLRs) play pivotal roles in the innate immune system and control inflammatory responses and adaptive immunity. We previously evaluated associations between TLR7 and TLR8 gene ...SNPs and susceptibility to hepatitis C virus (HCV) infection. Our results suggested that TLR7IVS2-151G and TLR8-129G alleles were present at higher frequency in males of an HCV-infected group as compared to a control group (24.1% vs. 14.4%, p = 0.028; 17.6% vs. 6.8%, p = 0.004, respectively). Based upon their recognition of single stranded viral RNA, this suggested that TLR7 and TLR8 played a significant role in anti-HCV immune responses. Here, we studied the functional effects of these polymorphisms by analyzing the mRNA expressions of TLR7 and TLR8 and cytokine production induced ex vivo by TLR7- and TLR8-specific agonists using whole blood of subjects with different genotypes. The percentage of CD14+ cells from those with an AG haplotype that expressed TLR7 and TLR8 was significantly lower, but higher in intensity compared to cells from those with GG and AC haplotypes. Cells from those with an AG haplotype produced more IFN-α and less amounts of pro-inflammatory cytokines upon stimulation. This suggests that variations in TLR7 and TLR8 genes might impair immune responses during HCV infection.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The Immunobiology of Nipah Virus Liew, Yvonne Jing Mei; Ibrahim, Puteri Ainaa S; Ong, Hui Ming ...
Microorganisms,
06/2022, Letnik:
10, Številka:
6
Journal Article
Recenzirano
Odprti dostop
Nipah virus (NiV) is a highly lethal zoonotic paramyxovirus that emerged in Malaysia in 1998. It is a human pathogen capable of causing severe respiratory infection and encephalitis. The natural ...reservoir of NiV, Pteropus fruit bats, remains a continuous virus source for future outbreaks, although infection in the bats is largely asymptomatic. NiV provokes serious disease in various mammalian species. In the recent human NiV outbreaks in Bangladesh and India, both bats-to-human and human-to-human transmissions have been observed. NiV has been demonstrated to interfere with the innate immune response via interferon type I signaling, promoting viral dissemination and preventing antiviral response. Studies of humoral immunity in infected NiV patients and animal models have shown that NiV-specific antibodies were produced upon infection and were protective. Studies on cellular immunity response to NiV infection in human and animal models also found that the adaptive immune response, specifically CD4+ and CD8+ T cells, was stimulated upon NiV infection. The experimental vaccines and therapeutic strategies developed have provided insights into the immunological requirements for the development of successful medical countermeasures against NiV. This review summarizes the current understanding of NiV pathogenesis and innate and adaptive immune responses induced upon infection.
Opioid-free anesthesia (OFA) represents an innovative approach that prioritizes patient safety, reduces the risks associated with opioid use, and seeks to enhance recovery. Few descriptions regarding ...the practical and implementation aspects exist. This review serves as a practical guide on OFA teaching and application. We briefly discuss the historical use of opioids in anesthesia, side effects and their consequences. We discuss pedagogical avenues and challenges, as well as implementation of OFA in less experienced settings. Opioid use in anesthesia originally coexisted with OFA. During the last decades, the advent of multimodal analgesia has resulted in decreased opioid dosages both before and after surgery. Recently, OFA increased in popularity, supported by meta-analyses, due to reduced nausea and vomiting, with a potential, even if limited, impact on pain. OFA, as part of rational prescribing, may contribute to a more patient-centered approach. Different strategies for OFA implementation coexist. Educational aspects, leadership, guidelines, local guidance, and training are all important. We propose a framework for OFA implementation with concrete options, including patient preparation, choice of OFA pharmacological agents (according to type of surgery and patient), and postoperative care. Whilst opioids still have an important place in pain management, they have brought harms that we cannot ignore. Evidence for using opioid-sparing and OFA techniques continues to emerge and there is a need to personalize more approaches. In this review, we provide evidence-based, relatively simple methods that can be used in implementing and delivering OFA.
Summary Toll-like receptors (TLRs) play a pivotal role in innate immunity, controlling inflammatory responses, and further development of adaptive immunity. Hepatitis virus can establish chronic ...infection, and the associated inflammatory responses are important determinants of virus-associated liver damage. However, the contributions of the host immune system to chronic presence of virus are not clear in patients with hepatitis virus infection. Chronic inflammatory conditions caused by persistent hepatitis virus infections and interferon (IFN)- γ -related immunopathology are known to be related to carcinogenesis. To gain insight into the role of immune modulation in the pathogenesis of hepatocellular carcinoma (HCC), we studied the expression of TLR7 in cancerous and non-cancerous liver tissue from 87 patients with HCC. Our results showed that TLR7 is significantly down-regulated in neoplastic hepatocytes ( P < .001), especially in the patients with hepatitis B (n = 52) or C (n = 24) virus infection. We confirmed this decreased TLR7 expression by quantitative analysis of mRNA using real-time reverse transcription-polymerase chain reaction in 26 liver specimens of HCC patients. Using serial deletion analysis of the TLR7 promoter, a hepatocyte-specific regulatory region was found at nucleotides −156 to −98 in the TLR7 promoter. Furthermore, the effects of IFN- γ on TLR7 expression in a hepatoma cell line (HepG2) were investigated in vitro. We demonstrated that IFN- γ significantly decreased TLR7 promoter activity and expression in a dose-dependent manner. We thus propose that hepatitis virus induces down-regulation of TLR7 gene expression through IFN- γ , thereby modulating inflammatory signaling in hepatoma cells.
Background:
Newborns admitted to neonatal units often require vascular access. Peripheral intravenous cannulas allow essential medication, fluids, and/or parenteral nutrition to be delivered. ...Peripheral intravenous cannulas are often associated with complications, such as extravasation, infiltration, phlebitis, leakage, spontaneous dislodgement, and catheter-associated blood stream infection.
Methods:
A secondary analysis of a randomized controlled trial evaluating standard replacement versus elective replacement (72–96 h) of peripheral intravenous cannula was conducted in a tertiary-level neonatal unit in Melbourne, Australia. The main outcome of this analysis was to assess the risk of combined adverse events associated with elective replacement of peripheral intravenous cannula. A cost analysis of the intervention was also conducted.
Results:
Combined adverse outcomes noted per infant were 48 (87.27%) in the standard replacement group versus 44 (75.86%) in the elective replacement group (RR 0.87; 95% CI 0.71–1.04, p = 0.15). In terms of combined adverse outcome per 1000 intravenous hours, there was a significant risk ratio of 0.81 in the elective group compared with the standard group (95% CI 0.65–0.98, p = 0.04). Gestation (adjusted odds ratio (AOR) 0.58; 95% CI 0.35–0.96, p = 0.03), male gender (AOR 4.65; 95% CI 1.07–20.28, p = 0.04), elective replacement (AOR 0.12; 95% CI 0.03–0.68, p = 0.01), and the total number of re-sites (AOR 27.84; 95% CI 4.61–168.18, p < 0.001) were significant risk factors associated with adverse events. There were also significantly higher costs involved with elective replacement.
Conclusion:
Elective replacement of peripheral intravenous cannulas was not shown to reduce the risk of combined adverse events. Elective peripheral intravenous cannula replacement also incurred a higher cost.
Tumor necrosis is a significant risk factor affecting patients' prognosis after liver resection (LR) for hepatocellular carcinoma (HCC). We aimed to develop a model with tumor necrosis as a variable ...to predict early tumor recurrence in HCC patients undergoing LR. Early tumor recurrence was observed in 161 (21.3%) patients. The concordance index of the proposed nomogram was 0.722. The calibration plots showed good agreement between nomogram predictions and actual observations of early recurrence. We developed a nomogram incorporating tumor necrosis to predict early recurrence of HCC after LR. Its predictive accuracy is satisfactory.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Background & Aims Non-alcoholic steatohepatitis (NASH) is recognized as the most severe form of non-alcoholic fatty liver disease, with likely progression to liver cirrhosis and hepatocellular ...carcinoma. However, there is no unified standard for diagnosis and therapeutics. This study aimed to characterize lipid transfer/metabolic proteins as non-invasive diagnostic markers, and to evaluate the therapeutic effects of phototherapy on the progression of NASH in rats. Methods Lewis rats given a choline-deficient and iron-supplemented l -amino acid-defined (CDAA) diet and Zucker fa/fa rats were used as a diet-induced and an obesity-related NASH models, respectively, with or without phototherapy. Results Serum apolipoprotein E and low molecular weight-adiponectin levels were gradually reduced and reached the lowest level at fatty liver/NASH stage both in CDAA diet-induced NASH model and in genetically obese model. Total-adiponectin levels were dramatically elevated after NASH was established in CDAA diet-induced NASH model. Phototherapy ameliorated hepatocyte apoptosis, inflammation, fibrosis, and insulin/leptin resistance caused by CDAA diet with alteration of the levels of lipid transfer/metabolic proteins and elevation of the circulating active form of vitamin D3 . Vitamin D3 supplementation ameliorated NASH progression in CDAA diet-induced NASH model. However, phototherapy failed to ameliorate the obesity and steatosis, suggesting that phototherapy may possess anti-inflammatory/fibrotic activity rather than anti-obesity/steatotic activity. Conclusions These results suggest that serum lipid transfer/metabolic proteins and vitamin D3 status may be effective biomarkers for non-invasive diagnosis of NASH progression, and that phototherapy may be a good complementary therapy for NASH because of its regulation of lipid transfer/metabolic proteins and vitamin D3.
Underrepresentation of Asian genomes has hindered population and medical genetics research on Asians, leading to population disparities in precision medicine. By whole-genome sequencing of 4,810 ...Singapore Chinese, Malays, and Indians, we found 98.3 million SNPs and small insertions or deletions, over half of which are novel. Population structure analysis demonstrated great representation of Asian genetic diversity by three ethnicities in Singapore and revealed a Malay-related novel ancestry component. Furthermore, demographic inference suggested that Malays split from Chinese ∼24,800 years ago and experienced significant admixture with East Asians ∼1,700 years ago, coinciding with the Austronesian expansion. Additionally, we identified 20 candidate loci for natural selection, 14 of which harbored robust associations with complex traits and diseases. Finally, we show that our data can substantially improve genotype imputation in diverse Asian and Oceanian populations. These results highlight the value of our data as a resource to empower human genetics discovery across broad geographic regions.
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•Discovery of 52 million novel variants by 13.7× WGS of 4,810 Singaporeans•Insights into population structure and evolutionary history of Asians•Identification of 20 loci under selection that are enriched for GWAS signals•Substantial improvement of imputation in diverse Asian and Oceanian populations
Because of Singapore’s unique history of immigration, whole-genome sequence analysis of 4,810 Singaporeans provides a snapshot of the genetic diversity across East, Southeast, and South Asia.
Background. We conducted a national point prevalence survey (PPS) to determine the prevalence of healthcare-associated infections (HAIs) and antimicrobial use (AMU) in Singapore acute-care hospitals. ...Methods. Trained personnel collected HAI, AMU, and baseline hospital- and patient-level data of adult inpatients from 13 private and public acute-care hospitals between July 2015 and February 2016, using the PPS methodology developed by the European Centre for Disease Prevention and Control. Factors independently associated with HAIs were determined using multivariable regression. Results. Of the 5415 patients surveyed, there were 646 patients (11.9%; 95% confidence interval CI, 11.1%–12.8%) with 727 distinct HAIs, of which 331 (45.5%) were culture positive. The most common HAIs were unspecified clinical sepsis (25.5%) and pneumonia (24.8%). Staphylococcus aureus (12.9%) and Pseudomonas aeruginosa (11.5%) were the most common pathogens implicated in HAIs. Carbapenem nonsusceptibility rates were highest in Acinetobacter species (71.9%) and P. aeruginosa (23.6%). Male sex, increasing age, surgery during current hospitalization, and presence of central venous or urinary catheters were independently associated with HAIs. A total of 2762 (51.0%; 95% CI, 49.7%–52.3%) patients were on 3611 systemic antimicrobial agents; 462 (12.8%) were prescribed for surgical prophylaxis and 2997 (83.0%) were prescribed for treatment. Amoxicillin/clavulanate was the most frequently prescribed (24.6%) antimicrobial agent. Conclusions. This survey suggested a high prevalence of HAIs and AMU in Singapore's acute-care hospitals. While further research is necessary to understand the causes and costs of HAIs and AMU in Singapore, repeated PPSs over the next decade will be useful to gauge progress at controlling HAIs and AMU.
Large well-differentiated hepatocellular carcinoma (HCC) ≥ 3 cm (defined as atypical HCC) is uncommon. We evaluated the characteristics and outcomes of atypical HCC patients underwent liver resection ...(LR).
This retrospective study enrolled patients who underwent LR for HCC from 2007 to 2017. Patient characteristics and overall survival (OS) were compared between patients with atypical HCC and patients with typical HCC (moderate-to-undifferentiated HCC ≥ 3 cm).
Among 598 patients, 51 (8.5%) had atypical HCC. Patients with atypical HCC had higher rates of non-hepatitis B or C infections (p = 0.02) and American Joint Committee on Cancer T1 pathology (p < 0.001), a lower rate of alpha-fetoprotein >20 ng/ml (p < 0.001) and a longer OS (p < 0.001) than those with typical HCC. Multivariate analysis showed that atypical HCC was associated with OS (HR = 0.50, 95% CI = 0.27–0.91, p = 0.02).
Patients with atypical HCC have a higher rate of non-hepatitis B or C infections and a lower rate of aggressive tumor biologic behavior. Atypical HCC is an independent predictor of OS.
•Large well-differentiated hepatocellular carcinoma (HCC) ≥ 3 cm (defined as atypical HCC) is uncommon.•We found that patients with atypical HCC who underwent resection have a higher rate of non-hepatitis B or C infections.•And a lower rate of aggressive tumor biologic behavior (i.e. a higher proportion of such patients have normal AFP and pathology T1).•Furthermore, atypical HCC is an independent predictor of better overall survival.
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