A comparative study of intestinal Pseudomonas aeruginosa in healthy individuals and ICU inpatients

The human intestinal tract is considered the most important reservoir of the opportunistic pathogens,including Pseudomonas aeruginosa,which is often overlooked but critical due to its antimicrobial resistance and virulence.Public health interventions to control this pathogen require a comprehensive understanding of its epidemiology and genomics.In the current study,we identified P.aeruginosa strains from 2,605 fecal samples collected between 2021 to 2022.Among these samples,574 were from ICU inpatients in Zhejiang province,while 2,031 were obtained from healthy individuals residing in ten different provinces in China.The prevalence of P.aerugi-nosa intestinal carriage was found to be higher in ICU inpatients(10.28%,95%CI:7.79%-12.76%)than that in healthy individuals(3.99%,81/2,031,95%CI:3.14%-4.84%).Similarly,the prevalence of carbapenem-resistant P.aeruginosa(CRPA)was higher in ICU inpatients(32.2%)compared to healthy individuals(7.41%).The population structure analy-sis of our isolates revealed a predominantly non-clonal distribution,with 41 distinct sequence types identified among 59 P.aeruginosa isolates from ICU inpatients and 38 different STs among 81 P.aeruginosa isolates from healthy individuals.These findings suggest that the individual acquisition of P.aeruginosa is more frequent than patient-to-patient transmission,as evidenced by the polyclonal population structure.Antimicrobial susceptibility testing and genome analysis indicated that P.aeruginosa strains from ICU inpatients exhibited significantly higher resistance rates to most antimicrobials and harbored a greater number of acquired resistance genes compared to strains from healthy individuals.Notably,in ICU inpatients,we identified three isolates of ST463,all of which shared the conserved Tn3-TnpR-ISKpn8-blaKPC-ISKpn6 genetic context.Additionally,five isolates carrying the qacE gene were also identified,these findings suggest that small-scale transmission events may still occur within the ICU setting,posing significant challenges for clinical management.With regard to virulence factors,we observed similar profiles between the two groups,except for phzA2,phzB2,and pilA,which were statistically higher in isolates from healthy individuals.This may be because the accumulating resistance mutations in ICU-derived P.aeruginosa are linked to a decrease in virulence.

Comment on “The diurnal variation pattern of choroidal thickness in macular region of young healthy female individuals using spectral domain optical coherence tomography”

Dear Editor,We have read and reviewed the article entitled＂The diurnal variation pattern of choroidal thickness in macular region of young healthy female individuals using spectral domain optical coherence tomography＂by Zhao et al^（[1]）with great interest.

Reproducibility of Heart Rate Recovery in Individuals with Low Heart Rate Recovery Response

Objective: To examine the reproducibility of HRR in healthy individuals with slow HRR response undergoing routine annual checkups. Method: HRR data (>18 b/min;Group 1 and 18 b/min;Group 2) were analyzed using a fixed-effects regression model adjusted for age and gender, including random effects group-specific slopes on age. Results: One hundred and thirteen individuals (56.5 ± 9.2 y), underwent 573 cumulative ESTs with an average of 5.1 ± 1.6 tests per individual during a 21-year retrospective follow-up. No differences were found in anthropometric measurements and blood variables. All individuals achieved 94% ± 7.7% of age-predicted HR max at peak EST. Group 2 demonstrated 38% of inconsistent HRR. Regression analysis demonstrated a decrease of 0.5 b/min, on average across individuals, in HRR per each extra year of age. The random effects showed an inter-subject SD level of 9.91 b/min and an SD on the age slope of 0.40 b/min/year. Conclusion: HRR showed low reproducibility in nearly 40% of tests, which was not reflected by the variation of HR nor in the slope of age during a 21-year retrospective follow-up.

Impact of corneal parameters on intraocular pressure measurements in different tonometry methods

AIM: To evaluate the impact of central corneal thickness(CCT) and corneal curvature on intraocular pressure(IOP) measurements performed by three different tonometers. METHODS: IOP in 132 healthy eyes of 66 participants was measured using three different tonometry techniques: Goldmann applanation tonometer(GAT), Pascal dynamic contour tonometer(DCT), and ICare rebound tonometer(RT). CCT and corneal curvature were assessed. RESULTS: In healthy eyes, DCT presents significantly higher values of IOP than GAT(17.34±3.69 and 15.27±4.06 mm Hg, P<0.0001). RT measurements are significantly lower than GAT(13.56±4.33 mm Hg, P<0.0001). Compared with GAT, DCT presented on average 2.51 mm Hg higher values in eyes with CCT<600 μm and 0.99 mm Hg higher results in eyes with CCT≥600 μm. The RT results were lower on average by 1.61 and 1.95 mm Hg than those obtained by GAT, respectively. Positive correlations between CCT in eyes with CCT<600 μm were detected for all IOP measurement techniques, whereas a similar relationship was not observed in eyes with thicker corneas. A correlation between IOP values and keratometry in the group with CCT<600 μm was not detected with any of the tonometry methods. In thicker corneas, a positive correlation was found for GAT and mean keratometry values(R=0.369, P=0.005). CONCLUSION: The same method should always be chosen for routine IOP control, and measurements obtained by different methods cannot be compared. All analysed tonometry methods are dependent on CCT;thus, CCT should be taken into consideration for both diagnostics and monitoring.

Common Postzygotic Mutational Signatures in Healthy Adult Tissues Related to Embryonic Hypoxia

Postzygotic mutations are acquired in normal tissues throughout an individual’s lifetime and hold clues for identifying mutagenic factors.Here,we investigated postzygotic mutation spectra of healthy individuals using optimized ultra-deep exome sequencing of the time-series samples from the same volunteer as well as the samples from different individuals.In blood,sperm,and muscle cells,we resolved three common types of mutational signatures.Signatures A and B represent clocklike mutational processes,and the polymorphisms of epigenetic regulation genes influence the proportion of signature B in mutation profiles.Notably,signature C,characterized by C>T transitions at GpCpN sites,tends to be a feature of diverse normal tissues.Mutations of this type are likely to occur early during embryonic development,supported by their relatively high allelic frequencies,presence in multiple tissues,and decrease in occurrence with age.Almost none of the public datasets for tumors feature this signature,except for 19.6%of samples of clear cell renal cell carcinoma with increased activation of the hypoxia-inducible factor 1(HIF-1)signaling pathway.Moreover,the accumulation of signature C in the mutation profile was accelerated in a human embryonic stem cell line with drug-induced activation of HIF-1α.Thus,embryonic hypoxia may explain this novel signature across multiple normal tissues.Our study suggests that hypoxic condition in an early stage of embryonic development is a crucial factor inducing C>T transitions at GpCpN sites;and individuals’genetic background may also influence their postzygotic mutation profiles.