Health care-associated infections such as Pseudomonas aeruginosa bacteremia pose a major clinical risk for hospitalized patients. However, these systemic infections are presumed to be a "dead-end" ...for P. aeruginosa and to have no impact on transmission. Here, we use a mouse infection model to show that P. aeruginosa can spread from the bloodstream to the gallbladder, where it replicates to extremely high numbers. Bacteria in the gallbladder can then seed the intestines and feces, leading to transmission to uninfected cage-mate mice. Our work shows that the gallbladder is crucial for spread of P. aeruginosa from the bloodstream to the feces during bacteremia, a process that promotes transmission in this experimental system. Further research is needed to test to what extent these findings are relevant to infections in patients.
Aim
The response rate to pioglitazone and the predictive factors for its effects on improving liver biochemistry in patients with steatotic liver disease (SLD) remain elusive, so we aimed to ...investigate these issues.
Methods
A 3‐year prospective cohort study of 126 Taiwanese patients with SLD treated with pioglitazone (15‐30 mg/day) was conducted. Phospholipase domain‐containing protein 3 I148M rs738409, methylenetetrahydrofolate reductase rs1801133, aldehyde dehydrogenase 2 (ALDH2) rs671 and lipoprotein lipase rs10099160 single nucleotide polymorphisms were assessed in the patients.
Results
Of 126 patients, 78 (61.9%) were men, and the mean and median ages were 54.3 and 56.5 years, respectively. Pioglitazone responders were defined as those with decreased alanine aminotransferase (ALT) levels at 6 months post‐treatment, and 105 (83.3%) patients were responders. Compared with non‐responders, responders were more frequently women and had higher baseline ALT levels. The proportion of patients with the ALDH2 rs671 GG genotype was lower among responders (38.6% vs. 66.6%, p = .028). Female sex odds ratio (OR): 4.514, p = .023 and baseline ALT level (OR: 1.015, p = .046; cut‐off level: ≥82 U/L) were associated with pioglitazone response. Among responders, the liver biochemistry and homeostasis model assessment of insulin resistance improved from 6 to 24 months post‐treatment. The total cholesterol levels decreased within 6 months, while increases in high‐density lipoprotein cholesterol levels and decreases in triglyceride levels and fibrosis‐4 scores were noted only at 24 months post‐treatment. The 2‐year cumulative incidences of cardiovascular events, cancers and hepatic events were similar between responders and non‐responders.
Conclusions
Regarding liver biochemistry, over 80% of Taiwanese patients with SLD had a pioglitazone response, which was positively associated with female sex and baseline ALT levels. Insulin resistance improved as early as 6 months post‐treatment, while liver fibrosis improvement was not observed until 24 months post‐treatment. The link between the pioglitazone response and the ALDH2 genotype warrants further investigation.
The impacts of patatin‐like phospholipase domain‐containing protein 3 (PNPLA3) I148M‐rs738409, methylenetetrahydrofolate reductase (MTHFR) Ala222Val‐rs1801133, and aldehyde dehydrogenase 2 (ALDH2) ...Glu504Lys‐rs671 on the outcomes of Taiwanese patients with steatotic liver disease (SLD) have remained elusive. An 8‐year prospective cohort study of patients with (n = 546) and without (n = 580) SLD (controls) was undertaken in a Taiwanese tertiary care center. The 546 SLD patients comprised 306 (56.0%) men and 240 (44.0%) women with mean ages of 53.3 and 56.4 years, respectively. Compared with the controls, SLD patients had an increased frequency of the PNPLA3 I148M‐rs738409 GG genotype (25.5 vs. 5.9%, p = 0.001). Among the SLD patients, 236 (43.1%) suffered cardiovascular events, 52 (9.5%) showed extrahepatic cancers, 13 (2.38%) experienced hepatic events, including hepatocellular carcinoma (n = 3, 0.5%) and liver cirrhosis (n = 8, 1.47%), and none died. The Fibrosis‐4 (FIB‐4) scores were associated with extrahepatic cancer (hazard ratio HR 1.325; 95% confidence interval CI, 1.038–1.691) and cirrhosis development (HR 1.532; 95% CI, 1.055–2.224), and the PNPLA3 I148M‐rs738409 G allele (β = 0.158, 95% CI, 0.054–0.325) was associated with the FIB‐4 score. Stratified analyses showed that the impact of the FIB‐4 score on extrahepatic cancer development was evident only in SLD patients with the PNPLA3 I148M‐rs738409 GG genotype (HR 1.543; 95% CI, 1.195–1.993) and not in patients with the GC or CC genotype. Moreover, the ALDH2 Glu504Lys‐rs671 G allele had a dose‐dependent effect on alcoholism, and the MTHFR and ALDH2 genotypes were not significantly associated with SLD patient outcomes. In conclusion, special vigilance should be exercised for emerging extrahepatic cancer in SLD patients with the PNPLA3 I148M‐rs738409 GG genotype and high FIB‐4 scores.
Link between gut microbiota and neonatal sepsis Lee, Chien-Chung; Chiu, Cheng-Hsun
Journal of the Formosan Medical Association,
June 2024, 2024-Jun, 2024-06-00, 20240601, 2024-06-01, Volume:
123, Issue:
6
Journal Article
Peer reviewed
Open access
In neonates, the gastrointestinal tract is rapidly colonized by bacteria after birth. Gut microbiota development is critical during the first few years of life. However, disruption of gut microbiota ...development in neonates can lead to gut dysbiosis, characterized by overcolonization by pathogenic bacteria and delayed or failed maturation toward increasing microbial diversity and Fermicutes dominance. Gut dysbiosis can predispose infants to sepsis. Pathogenic bacteria can colonize the gut prior to sepsis and cause sepsis through translocation. This review explores gut microbiota development in neonates, the evidence linking gut dysbiosis to neonatal sepsis, and the potential role of probiotics in gut microbiota modulation and sepsis prevention.
Without the need of any transmission line, a very compact decoupling network based on reactive lumped elements is presented for a two-element closely spaced array. The lumped network, consisting of ...two series and four shunt elements, can be analytically designed using the even-odd mode analysis. In the even mode, the half-circuit of the decoupling network is identical to an L-section matching network, while in the odd mode it is equivalent to a π-section one. The proposed decoupling network can deal with the matching conditions of the even and odd modes independently so as to simultaneously achieve good impedance matching and port isolation of the whole antenna array. The design principle, formulation, and experimental results including the radiation characteristics are introduced.
Elizabethkingia meningoseptica is a hazardous bacterium for agriculture production and human health. The present study identified E. meningoseptica from the bullfrog, human and reference strain BCRC ...10677 by API 20NE, 50S ribosome protein L27 sequencing and pulse field gel electrophoresis to differentiate isolates of E. meningoseptica from aquatic animals and humans. All isolates from bullfrogs and humans were identified as E. meningoseptica by DNA sequencing with 98.8%-100% sequence identity. E. meningoseptica displayed significant genetic diversity when analysed using pulsed-field gel electrophoresis (PFGE). There were six distinct pulsotypes, including one pulsotype found in bullfrog isolates and five pulsotypes found in human isolates. However, E. meningoseptica from bullfrog exhibited one genotype only by PFGE. Overall, molecular epidemiological analysis of PFGE results indicated that the frog E. meningoseptica outbreaks in Taiwan were produced by genetically identical clones. The bullfrog isolates were not genetically related to other E. meningoseptica from human and reference isolates. This research provided the first comparisons of biochemical characteristics and genetic differences of E. meningoseptica from human and bullfrog isolates.
Acute diarrhea is a major cause of childhood morbidity and an economic burden for families. The aim of this study is to explore the effect of probiotics on clinical symptoms, intestinal microbiota, ...and inflammatory markers during childhood diarrhea.
Children (
= 81) aged six months to six years (mean age 2.31 years) hospitalized for acute diarrhea were randomized to receive probiotics (
variety
;
= 42) or no probiotics (
= 39) orally twice daily for seven days. Feces samples were also collected to evaluate microbial content using a traditional agar plate and next-generation sequencing. Immunoglobulin A (IgA), lactoferrin, and calprotectin were determined by enzyme-linked immunosorbent assay (ELISA) and compared in different groups. Other clinical symptoms or signs, including fever, vomiting, diarrhea, abdominal pain, bloated abdomen, daily intake, appetite, and body weight were also assessed.
Data were collected from 81 individuals across three different time points. Total fecal IgA levels in fecal extracts of the probiotics group were higher than those in the control group, reaching statistical significance (
0.05). Concentrations of fecal lactoferrin and calprotectin were significantly downregulated in patients with probiotic
variety
(Lc) consumption compared to those of the control (
0.05). Probiotic Lc administration may be beneficial for gut-microbiota modulation, as shown by the data collected at one week after enrollment. Counts of
and
species were elevated in stool culture of the probiotic group. Appetite and oral intake, body-weight gain, abdominal pain, bloating, as well as bowel habits (diarrhea) were much better in children receiving probiotics compared with those in the control group.
Fecal IgA increased during acute diarrhea under Lc treatment; in contrast, fecal lactoferrin and calprotectin were downregulated during acute diarrhea under Lc treatment. Probiotic Lc may be a useful supplement for application in children during acute diarrhea to reduce clinical severity and intestinal inflammatory reaction.
Children are susceptible to severe or fatal enterovirus 71 (EV71) infections. We aimed to evaluate the efficacy, safety, and immunogenicity of EV71vac, an aluminium phosphate-adjuvanted inactivated ...EV71 vaccine in children aged 2–71 months.
We did a randomised, double-blinded, placebo-controlled, phase 3 trial at five hospitals in Taiwan and two in Vietnam. Children aged 2–71 months were stratified by country and age, and randomly assigned (1:1) to receive two doses of EV71vac or placebo via intramuscular injection 56 days apart. Children aged 2–23 months received a third booster dose on day 366. The primary endpoint was the clinical efficacy of the total vaccinated cohort against EV71-associated diseases during the follow-up period, from 14 days after the second dose to when 15 cases of EV71 infections were confirmed in the per-protocol population. Our safety analysis included all participants who received at least one dose of EV71vac. This trial is registered with ClinicalTrials.gov, NCT03865238, and is complete.
Between April 23 and Dec 25, 2019, of 3663 children assessed, 3061 were randomly assigned, of whom 3049 were vaccinated: 1521 children in the EV71vac group and 1528 in the placebo group. By May 20, 2021, our primary efficacy analysis included 2959 children, with 1476 children in the EV71vac group and 1483 children in the placebo group. The vaccine efficacy of EV71vac was 96·8% (95% CI 85·5–100) against EV71 associated diseases (p<0·0001). The percentage of participants who reported solicited adverse events were similar in both groups: 865 (56·9%) in the EV71vac group and 852 (55·8%) in the placebo group. Almost all reported solicited adverse events were mild and self-limited.
EV71vac is safe, well-tolerated, and highly effective in preventing EV71 associated diseases in children aged 2–71 months.
Medigen Vaccine Biologics and A+ Industrial Innovative R&D Program of the Ministry of Economic Affairs, Taiwan.
This paper proposes AgriTalk, an inexpensive Internet of Things (IoT) platform for precision farming of soil cultivation. We conduct experiments on turmeric cultivation, which indicates that the ...turmeric quality is significantly enhanced through AgriTalk. Specifically, the curcumin concentration is up to 4500-5500 mg/100 g, which is five times more than existing products. We demonstrate how to intuitively configure the connections between the sensors and the actuators with the desired farming intelligence, and to effectively maintain AgriTalk for precision farming. We conduct measurement, analytic analysis, and simulation experiments to investigate the IoT message delays of AgriTalk. This paper indicates that the delays for automatic control and automatic-manual control switching with long distances (more than 30 km) are very short (less than 0.2 s) and AgriTalk can easily respond to quick and dynamic change of the field environment conditions in soil cultivation.
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