Regulation of candidalysin underlies Candida albicans persistence in intravascular catheters by modulating NETosis.

Candida albicans is a leading cause of intravascular catheter-related infections. The capacity for biofilm formation has been proposed to contribute to the persistence of this fungal pathogen on catheter surfaces. While efforts have been devoted to identifying microbial factors that modulate C. albicans biofilm formation in vitro, our understanding of the host factors that may shape C. albicans persistence in intravascular catheters is lacking. Here, we used multiphoton microscopy to characterize biofilms in intravascular catheters removed from candidiasis patients. We demonstrated that, NETosis, a type of neutrophil cell death with antimicrobial activity, was implicated in the interaction of immune cells with C. albicans in the catheters. The catheter isolates exhibited reduced filamentation and candidalysin gene expression, specifically in the total parenteral nutrition culture environment. Furthermore, we showed that the ablation of candidalysin expression in C. albicans reduced NETosis and conferred resistance to neutrophil-mediated fungal biofilm elimination. Our findings illustrate the role of neutrophil NETosis in modulating C. albicans biofilm persistence in an intravascular catheter, highlighting that C. albicans can benefit from reduced virulence expression to promote its persistence in an intravascular catheter.

Comparison of ERIC carbapenem-resistant Enterobacteriaceae test, BD Phoenix CPO detect panel, and NG-test CARBA 5 for the detection of main carbapenemase types of carbapenem-resistant Enterobacterales.

BACKGROUND: This study aimed to assess the performance of three commercial panels, the ERIC Carbapenem-Resistant Enterobacteriaceae Test (ERIC CRE test), the NG-Test CARBA 5 (NG CARBA 5), and the BD Phoenix CPO Detect Panel (CPO panel), for the detection of main types of carbapenemases among carbapenem-resistant Enterobacterales (CRE). METHODS: We collected 502 isolates of carbapenem-resistant Enterobacterales (CRE) demonstrating intermediate or resistant profiles to at least one carbapenem antibiotic (ertapenem, imipenem, meropenem, or doripenem). Carbapenemase genes and their specific types were identified through multiplex PCR and sequencing methods. Subsequently, the ERIC CRE test, CPO panel, and NG CARBA 5 assay were conducted on these isolates, and the results were compared with those obtained from multiplex PCR. RESULTS: The results indicated that the ERIC CRE test exhibited an overall sensitivity and specificity of 98.1% and 93.6%, respectively, which were comparable to 99.1% and 90.6% for the NG CARBA 5. However, the CPO panel demonstrated a sensitivity of only 56.2% in identifying Ambler classes, exhibiting the poorest sensitivity for class A. Moreover, while the ERIC CRE test outperformed the NG CARBA 5 in identifying multi-gene isolates with multiple carbapenemase-encoding genes, the CPO panel failed to accurately classify these isolates. CONCLUSIONS: Our findings support the utilization of the ERIC CRE test as one of the methods for detecting carbapenemases in clinical laboratories. Nonetheless, further optimization is imperative for the CPO panel to enhance its accuracy in determining carbapenemase classification and address limitations in detecting multi-gene isolates.

Assisted Reproductive Technology, Multiple Births, and Perinatal Outcomes in Taiwan from 2001 to 2020.

OBJECTIVE: To investigate the effect of the Assisted Reproduction Act, implemented in 2007 in Taiwan to reduce the number of embryos to transfer, on the trends over time regarding the rate of multiple births, preterm delivery, low birth weight (LBW), and small for gestational age (SGA) among deliveries using assisted reproductive technology (ART). STUDY DESIGN: From the Birth Reporting Registry and the Assisted Reproduction Registry, we retrieved data of 4,016,530 live birth deliveries between 2001 and 2020; among them 71,000 (1.77%) were after ART. We calculated the rate of multiples and perinatal outcomes per 1000 deliveries annually from 2001 to 2020 for deliveries using and not using ART and computed the population attributable risk (PAR). We performed interrupted time series to assess the effect of the intervention, ie, the Assisted Reproduction Act. RESULTS: The proportion of deliveries following ART was 0.57% in 2001 and increased to 4.03% in 2020. After the intervention, there were decreasing trends over time for rates of multiples (-10.63 per year, p<0.001), preterm delivery (-6.74, p = 0.003), LBW (-9.38, p<0.001) and SGA (-4.48, p = 0.001) among ART deliveries. There was also an immediate decrease right after intervention (-53.45, p = 0.005) for SGA after ART. The PAR trends before and after intervention were both increasing for all outcomes. CONCLUSIONS: The Assisted Reproduction Act in Taiwan was associated with a decreasing trend of multiples, preterm delivery, LBW, and SGA over time since 2008 among ART deliveries. In particular, there was an immediate decrease of SGA right after the intervention.

The Association between Bone Mineral Density and Risk of Mortality: A Prospective Cohort Study of 233,397 Taiwanese.

PURPOSE: Osteoporosis is an important public health challenge given its high prevalence in western populations and the prevalence has shown an upward trend in recent decades in Asia. However, epidemiological evidence on the association between bone mineral density (BMD) and mortality risk in the Asian population is sparse. METHODS: The Cox proportional hazards model and cause-specific hazard models were used to investigate the association of BMD with the risk of all-cause mortality and cause-specific mortality. RESULTS: The present study comprised of 3,332,207 person-years with a median follow-up of 14.6 years. 27,508 participants (15,967 men and 11,541 women) died among 233,397 participants (112,348 men and 121,049 women) during the follow-up period. Compared to those with normal BMD level, both men and women with low BMD had a significantly higher risk of all-cause, cardiovascular disease (CVD), and cancer mortality after adjusting for the covariates. [For men with osteoporosis: all-cause: 1.37 (1.27-1.49); CVD: 1.28 (1.08-1.52); cancer: 1.29 (1.12-1.49); For women with osteoporosis: all-cause: 1.72 (1.63-1.82); CVD: 1.85 (1.64-2.08); cancer: 1.47 (1.35-1.61)]. The P for interactions for BMD with sex were significant for all-cause and CVD mortality. The adverse effects of BMD on the risk of all-cause and CVD were higher in women than in men [men vs. women: all-cause: 1.37 (1.27-1.49) vs. 1.72 (1.63-1.82); CVD: 1.28 (1.08-1.52) vs. 1.85 (1.64-2.08)]. In the nonlinear dose-response analyses, the association between BMD increments and all-cause mortality risk shows an L-shaped pattern in men and a similar U-shaped trend in women (P for non-linear association: <0.001). Likewise, a similar L-shaped association was observed between BMD levels and cancer mortality risk in men. CONCLUSIONS: Low BMD had an increased risk of all-cause, CVD, and cancer mortality in both men and women. Women had a stronger positive association between low BMD and an increased risk of all-cause and CVD mortality compared to men.

Study of a Deep Convolution Network with Enhanced Region Proposal Network in the Detection of Cancerous Lung Tumors.

A deep convolution network that expands on the architecture of the faster R-CNN network is proposed. The expansion includes adapting unsupervised classification with multiple backbone networks to improve the Region Proposal Network in order to improve accuracy and sensitivity in detecting minute changes in images. The efficiency of the proposed architecture is investigated by applying it to the detection of cancerous lung tumors in CT (computed tomography) images. This investigation used a total of 888 images from the LUNA16 dataset, which contains CT images of both cancerous and non-cancerous tumors of various sizes. These images are divided into 80% and 20%, which are used for training and testing, respectively. The result of the investigation through the experiment is that the proposed deep-learning architecture could achieve an accuracy rate of 95.32%, a precision rate of 94.63%, a specificity of 94.84%, and a high sensitivity of 96.23% using the LUNA16 images. The result shows an improvement compared to a reported accuracy of 93.6% from a previous study using the same dataset.

3D-Printed proangiogenic patches of photo-crosslinked gelatin and polyurethane hydrogels laden with vascular cells for treating vascular ischemic diseases.

Engineering vascularized tissues remains a promising approach for treating ischemic cardiovascular diseases. The availability of 3D-bioprinted vascular grafts that induce therapeutic angiogenesis can help avoid necrosis and excision of ischemic tissues. Here, using a combination of living cells and biodegradable hydrogels, we fabricated 3D-printed biocompatible proangiogenic patches from endothelial cell-laden photo-crosslinked gelatin (EC-PCG) bioink and smooth muscle cell-encapsulated polyurethane (SMC-PU) bioink. Implantation of 3D-bioprinted proangiogenic patches in a mouse model showed that EC-PCG served as an angiogenic capillary bed, whereas patterned SMC-PU increased the density of microvessels. Moreover, the assembled patterns between EC-PCG and SMC-PU induced the geometrically guided generation of microvessels with blood perfusion. In a rodent model of hindlimb ischemia, the vascular patches rescued blood flow to distal tissues, prevented toe/foot necrosis, promoted muscle remodeling, and increased the capillary density, thereby improving the heat-escape behavior of ischemic animals. Thus, our 3D-printed vascular cell-laden bioinks constitute efficient and scalable biomaterials that facilitate the engineering of vascular patches capable of directing therapeutic angiogenesis for treating ischemic vascular diseases.

The joint effect of long-term exposure to multiple air pollutants on non-accidental and cause-specific mortality: A longitudinal cohort study.

The long-term joint impacts of fine particulate matter (PM2.5), nitrogen dioxide (NO2), and ozone (O3) on mortality are inconclusive. To bridge this research gap, we included 283,568 adults from the Taiwan MJ cohort between 2005 and 2016 and linked with the mortality data until 31 May 2019. Participants' annual average exposures to PM2.5, NO2, and O3 were estimated using satellite-based spatial-temporal models. We applied elastic net-regularised Cox models to construct a weighted environmental risk score (WERS) for the joint effects of three pollutants on non-accidental, cardiovascular, and cancer mortality and evaluated the contribution of each pollutant. The three pollutants jointly raised non-accidental mortality risk with a WERS hazard ratio (HR) of 1.186 (95% CI: 1.118-1.259) per standard deviation increase in each pollutant and weights of 72.8%, 15.2%, and 12.0% for PM2.5, NO2, and O3, respectively. The WERS increased cardiovascular death risk [HR: 1.248 (1.042-1.496)], with PM2.5 as the first contributor and O3 as the second. The WERS also elevated the cancer death risk [HR: 1.173 (1.083-1.270)], where PM2.5 played the dominant role and NO2 ranked second. Coordinated control of these three pollutants can optimise the health benefits of air quality improvements.

Synthesis of novel chitosan/sodium hyaluronate/iridium hydrogel nanocomposite for wound healing application.

A novel chitosan/sodium hyaluronate/iridium (CHI/SH/Ir) hydrogel nanocomposite with a unique microstructure containing vertically aligned pores is fabricated via an electrophoresis technique. The formation of orderly vertical pores in CHI/SH/Ir hydrogel nanocomposite is due to the confinement of hydrogen bubbles produced from the water electrolysis during electrophoresis that limits their lateral movement and coalescence. In a wet state, the diameter for the vertical pores is 600-700 µm. With a thickness of 500 µm, the CHI/SH/Ir hydrogel nanocomposite exhibits a porosity of 76.7 % and a water uptake of 350 %. Its tensile strength is almost doubled to 8.7 MPa, as compared to that of counterpart without the addition of iridium. In CHI/SH/Ir hydrogel nanocomposite, the iridium nanoparticles are homogeneously distributed with an average size of 3 nm. The CHI/SH/Ir electrophoresis suspension exhibits a negligible cytotoxicity. In cell migration test using the human keratinocytes HaCaT cells, the CHI/SH/Ir hydrogel nanocomposite reveals a relative migration of 122.15 ± 9.02 % (p < 0.001) as compared to the blank sample. The presence of vertically aligned pores with the use of SH and iridium nanoparticles indicates a promising opportunity in wound healing application.

Clinical effectiveness of nirmatrelvir plus ritonavir on the short- and long-term outcome in high-risk children with COVID-19.

This study investigated the clinical effectiveness of nirmatrelvir plus ritonavir (NMV-r) on short-term outcome and the risk of postacute sequelae of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection (PASC) among pediatric patients with coronavirus disease 2019 (COVID-19). This retrospective cohort study used the TriNetX research network to identify pediatric patients between 12 and 18 years with COVID-19 between January 1, 2022 and August 31, 2023. The propensity score matching (PSM) method was used to match patients receiving NMV-r (NMV-r group) with those who did not receive NMV-r (control group). Two cohorts comprising 633 patients each (NMV-r and control groups), with balanced baseline characteristics, were identified using the PSM method. During the initial 30 days, the NMV-r group showed a lower incidence of all-cause hospitalization, mortality, or ED visits (hazard ratio [HR] = 0.546, 95% confidence interval [CI]: 0.372-0.799, p = 0.002). Additionally, the NMV-r group had a significantly lower risk of all-cause hospitalization compared with the control group (HR = 0.463, 95% CI: 0.269-0.798), with no deaths occurring in either group. In the 30-180-day follow-up period, the NMV-r group exhibited a non-significantly lower incidence of post-acute sequelae of SARS-CoV-2 infection (PASC), encompassing symptoms such as fatigue, cardiopulmonary symptoms, pain, cognitive impairments, headache, dizziness, sleep disorders, anxiety, and depression, compared to the control group. This study underscores the potential effectiveness of NMV-r in treating high-risk pediatric patients with COVID-19, demonstrating significant reductions in short-term adverse outcomes such as emergency department visits, hospitalization, or mortality within the initial 30-day period. Additionally, NMV-r shows promise in potentially preventing the development of PASC.

Dextromethorphan moderates reward deficiency associated with central serotonin transporter availability in 3,4-methylenedioxy-methamphetamine-treated animals.

BACKGROUND: The neurotoxicity of 3,4-methylenedioxy-methamphetamine (MDMA) to the serotonergic system is well-documented. Dextromethorphan (DM), an antitussive drug, decreased morphine- or methamphetamine (MA)-induced reward in rats and may prevent MDMA-induced serotonergic deficiency in primates, as indicated by increased serotonin transporter (SERT) availability. We aimed to investigate the effects of DM on reward, behavioral sensitization, and neurotoxicity associated with loss of SERT induced by chronic MDMA administration in rats. METHODS: Conditioned place preference (CPP) and locomotor activity tests were used to evaluate drug-induced reward and behavioral sensitization; 4-[ 18 F]-ADAM/animal-PET and immunohistochemistry were used to explore the effects of DM on MDMA-induced loss of SERT. RESULTS: MDMA significantly reduced SERT binding in the rat brain; however, co-administration of DM significantly restored SERT, enhancing the recovery rate at day 14 by an average of ~23% compared to the MDMA group. In confirmation of the PET findings, immunochemistry revealed MDMA reduced SERT immunoactivity in all brain regions, whereas DM markedly increased the serotonergic fiber density after MDMA induction. CONCLUSION: Behavioral tests and in vivo longitudinal PET imaging demonstrated the CPP indexes and locomotor activities of the reward system correlate negatively with PET 4-[ 18 F]ADAM SERT activity in the reward system. Our findings suggest MDMA induces functional abnormalities in a network of brain regions important to decision-making processes and the motivation circuit. DM may exert neuroprotective effects to reverse MDMA-induced neurotoxicity.

Epidemiology and antimicrobial susceptibility profiles of Enterobacterales causing bloodstream infections before and during COVID-19 pandemic: Results of the Study for Monitoring Antimicrobial Resistance Trends (SMART) in Taiwan, 2018-2021.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic has contributed to the spread of antimicrobial resistance, including carbapenem-resistant Enterobacterales. METHODS: This study utilized data from the Study for Monitoring Antimicrobial Resistance Trends (SMART) surveillance program in Taiwan. Enterobacterales from patients with bloodstream infections (BSIs) were collected and subjected to antimicrobial susceptibility testing and ß-lactamase gene detection using a multiplex PCR assay. Statistical analysis was conducted to compare susceptibility rates and resistance genes between time periods before (2018-2019) and during the COVID-19 pandemic (2020-2021). RESULTS: A total of 1231 Enterobacterales isolates were collected, predominantly Escherichia coli (55.6%) and Klebsiella pneumoniae (29.2%). The proportion of nosocomial BSIs increased during the COVID-19 pandemic (55.5% vs. 61.7%, p < 0.05). Overall, susceptibility rates for most antimicrobial agents decreased, with Enterobacterales from nosocomial BSIs showing significantly lower susceptibility rates than those from community-acquired BSIs. Among 123 Enterobacterales isolates that underwent molecular resistance mechanism detection, ESBL, AmpC ß-lactamase, and carbapenemase genes were detected in 43.1%, 48.8% and 16.3% of the tested isolates, respectively. The prevalence of carbapenemase genes among carbapenem-resistant Enterobacterales increased during the pandemic, although the difference was not statistically significant. Two novel ß-lactamase inhibitor combinations, imipenem-relebactam and meropenem-vaborbactam, preserved good efficacy against Enterobacterales. However, imipenem-relebactam showed lower in vitro activity against imipenem-non-susceptible Enterobacterales than that of meropenem-vaborbactam. CONCLUSIONS: The COVID-19 pandemic appears to be associated with a general decrease in antimicrobial susceptibility rates among Enterobacterales causing BSIs in Taiwan. Continuous surveillance is crucial to monitor antimicrobial resistance during the pandemic and in the future.

A simple scoring algorithm based on intrinsic capacity for functional ability in community-dwelling older adults in Taiwan.

BACKGROUND: Intrinsic capacity (IC) is a comprehensive indicator of the overall well-being of older adults, and assessing of IC can help identify early stage of disability and tailor intervention to individual needs. However, there is a lack of effective and simple IC assessment tools. This study aimed to establish predictive scoring algorithms of IC to identify older adults at high risk of impaired functional ability. METHODS: We conducted a cross-sectional study in Southern Taiwan, measuring IC using 7 subitems: cognition, locomotion, vitality, vision, hearing, psychological well-being, and medication usage were measured. Functional ability outcomes included frailty, basic activities of daily living, and instrumental activities of daily living (IADL). The capability of 7 domains of IC in predicting functional ability was assessed by multivariable logistic regression. The prediction of capability of scoring algorithms was indicated by receiver operating characteristic (AUC) curves and measures of sensitivity and specificity. RESULTS: A total of 1,152 older adults were recruited and analyzed. Locomotion emerged as a significant predictor of IADL disability and worsening frailty. The IC-based weighted scoring algorism for predicting IADL demonstrated satisfactory capability (AUC: 0.80), as did the algorithm for predicting worsening frailty (AUC: 0.90). The optimal cutoff points for predicting IADL disability and frailty worse were estimated respectively at 13 and 16, with sensitivity/specificity values of 0.74/0.75 for the IADL prediction algorithm and 0.92/0.77 for the frailty prediction algorithm. CONCLUSION: Our 7-domain IC screening tool proves to be sensitive and practical for early identification of functional disability and frailty among community-dwelling older adults in Taiwan.

High-security learning-based optical encryption assisted by disordered metasurface.

Artificial intelligence has gained significant attention for exploiting optical scattering for optical encryption. Conventional scattering media are inevitably influenced by instability or perturbations, and hence unsuitable for long-term scenarios. Additionally, the plaintext can be easily compromised due to the single channel within the medium and one-to-one mapping between input and output. To mitigate these issues, a stable spin-multiplexing disordered metasurface (DM) with numerous polarized transmission channels serves as the scattering medium, and a double-secure procedure with superposition of plaintext and security key achieves two-to-one mapping between input and output. In attack analysis, when the ciphertext, security key, and incident polarization are all correct, the plaintext can be decrypted. This system demonstrates excellent decryption efficiency over extended periods in noisy environments. The DM, functioning as an ultra-stable and active speckle generator, coupled with the double-secure approach, creates a highly secure speckle-based cryptosystem with immense potentials for practical applications.

Assessment of DNA/RNA Deregulation in Cancer Using 99mTc-Labeled Thiopurine.

Background: DNA biomarkers are useful for the assessment of tumor cell proliferation. The authors aimed to synthesize a thiopurine-based ligand for evaluation of nuclear uptake and tumor localization. Materials and Methods: A 2-hydroxypropyl spacer was incorporated between a chelator (cyclam) and thiopurine ligand to produce SC-06-L1. In vitro cellular uptake and the cell/media ratios of [99mTc]Tc-SC-06-L1 were assessed in breast (MCF-7, MDA-MB-231) and ovarian (TOV-112D, OVCAR3) cancer cells. The nuclear and cytosolic uptake ratio of [99mTc]Tc-SC-06-L1 was determined in OVCAR-3 and MCF-7 cells. Cytotoxicity assays and flow cytometric analysis of cell cycle apoptosis were conducted in cancer cells treated with SC-06-L1. Imaging was conducted in tumor-bearing mice; fluorine-18-2'-fluorodeoxyglucose ([18F]FDG) was used as a control. Results: The radiochemical purity of [99mTc]Tc-SC-06-L1 was >95%. [99mTc]Tc-SC-06-L1 exhibited higher cell-to-media ratios than [18F]FDG in cancer cells. [99mTc]Tc-SC-06-L1 had high uptake in the nuclear fractions in OVCAR-3 and MCF-7 cells, with nuclear/cytosolic ratios of 8 and 2, respectively. Cytotoxicity assays showed that SC-06-L1 was non-toxic compared with azathioprine in breast and ovarian cancer cells. Conclusions: [99mTc]Tc-SC-06-L1 was stable and involved in nuclear activities. [99mTc]Tc-SC-06-L1 showed non-toxic to cancer cells and exhibited fast kinetic uptake patterns for tumor imaging. [99mTc]Tc-SC-06-L1 represents a promising biomarker for imaging purine pathway-directed systems.

In vitro antimicrobial susceptibility data of global meropenem-resistant Acinetobacter baumannii isolates causing pneumonia: Data from the Antimicrobial Testing Leadership and Surveillance Program, 2014-2021, and re-estimations of susceptibility breakpoints and appropriate dosages of important antibiotics for pneumonia treatment.

OBJECTIVES: To evaluate the susceptibility of globally pneumonia-causing meropenem-resistant (MEM-R) Acinetobacter baumannii isolates against important antibiotics and estimate appropriate dosages of indicated antibiotics. METHODS: We extracted the 2014-2021 Antimicrobial Testing of Leadership Surveillance database regarding the susceptibility of MEM-R A. baumannii isolates causing pneumonia against important antibiotics. The susceptibility and carbapenemase-encoding gene (CPEG) data of pneumonia-causing MEM-R A. baumannii isolates from patients hospitalized in intensive care units of five major regions were analyzed. The susceptibility breakpoints (SBP) recommended by the Clinical and Laboratory Standards Institute (CLSI) in 2022, other necessary criteria [SBP of MIC for colistin, 2 mg/L, in the CLSI 2018; and cefoperazone-sulbactam (CFP-SUL), 16 mg/L], and the pharmacokinetic and pharmacodynamic data of indicated antibiotics were employed. RESULTS: Applying the aforementioned criteria, we observed the susceptible rates of colistin, minocycline, and CFP-SUL against the pneumonia-causing MEM-R A. baumannii isolates globally (n = 2905) were 93.2%, 69.1%, and 26.3%, respectively. Minocycline was significantly more active in vitro (MIC ≤4 mg/L) against the pneumonia-causing MEM-R A. baumannii isolates collected from North and South America compared to those from other regions (>90% vs. 58-72%). Additionally, blaOXA-23 and blaOXA-72 were the predominant CPEG in pneumonia-causing MEM-R A. baumannii isolates. CONCLUSIONS: After deliberative estimations, dosages of 200 mg minocycline intravenously every 12 h (SBP, 8 mg/L), 100 mg tigecycline intravenously every 12 h (SBP, 1 mg/L), and 160 mg nebulized colistin methanesulphonate every 8 h (SBP, 2 mg/L) are needed for the effective treatment of pneumonia-causing MEM-R A. baumannii isolates.

A 19-year longitudinal study to characterize carbapenem-nonsusceptible Acinetobacter isolated from patients with bloodstream infections and the contribution of conjugative plasmids to carbapenem resistance and virulence.

BACKGROUND: This study aimed to characterize carbapenem-nonsusceptible Acinetobacter (CNSA) isolated from patients with bacteremia from 1997 to 2015. METHODS: A total of 173 CNSA (12.3%) was recovered from 1403 Acinetobacter isolates. The presence of selected ß-lactamase genes in CNSA was determined by PCR amplification. The conjugation test was used to determine the transferability of metallo-ß-lactamase (MBL)-carrying plasmids. Whole genome sequencing in combination with phenotypic assays was carried out to characterize MBL-plasmids. RESULTS: In general, a trend of increasing numbers of CNSA was observed. Among the 173 CNSA, A. baumannii (54.9%) was the most common species, followed by A. nosocomialis (23.1%) and A. soli (12.1%). A total of 49 (28.3%) CNSA were extensively drug-resistant, and all were A. baumannii. The most common class D carbapenemase gene in 173 CNSA was blaOXA-24-like (32.4%), followed by ISAba1-blaOXA-51-like (20.8%), ISAba1-blaOXA-23 (20.2%), and IS1006/IS1008-blaOXA-58 (11.6%). MBL genes, blaVIM-11,blaIMP-1, and blaIMP-19 were detected in 9 (5.2%), 20 (11.6%), and 1 (0.6%) CNSA isolates, respectively. Transfer of MBL genes to AB218 and AN254 recipient cells was successful for 7 and 6 of the 30 MBL-plasmids, respectively. The seven AB218-derived transconjugants carrying MBL-plasmids produced less biofilm but showed higher virulence to larvae than recipient AB218. CONCLUSIONS: Our 19-year longitudinal study revealed a stable increase in CNSA during 2005-2015. blaOXA-24-like, ISAba1-blaOXA-51-like, and ISAba1-blaOXA-23 were the major determinants of Acinetobacter carbapenem resistance. MBL-carrying plasmids contribute not only to the carbapenem resistance but also to A. baumannii virulence.

Trajectories of body mass index before the diagnosis of type 2 diabetes in a cohort of Taiwanese adults.

BACKGROUND: Although the prevalence of overweight/obesity is lower in Asian countries, the risk of type 2 diabetes (T2DM) is disproportionally higher. We identified and characterized the trajectory patterns of body mass index (BMI) before the onset of T2DM in a Taiwanese population. METHODS: Using the Taiwan MJ cohort study, we sampled the health examination data of 22,934 participants, including 7618 cases of T2DM and 15,316 controls. We used latent class trajectory analysis to identify distinct groups of pre-disease BMI trajectory. To compare the trajectories of cardiometabolic risk factors among different groups, we used linear mixed-effects models. RESULTS: These 22,934 participants included 13,074 men (57%) and 9860 women (43%) who were on average followed for 9.0 years. We identified three distinct pre-disease BMI trajectories in cases: "stable overweight" (n = 7016, 92.1%), "weight gain" (n = 333, 4.4%) and "obesity" (n = 269, 3.5%). The "stable overweight" group had a mean BMI of 24.6 kg/m2 at 15 years prior to diagnosis, had a 1.2 unit increase during follow-up, and had a mean BMI of 25.8 kg/m2 at the time of diagnosis. The "weight gain" group had the most increasing trends in blood pressure/low-density lipoprotein cholesterol over time. CONCLUSION: The BMI trajectory patterns among individuals who later developed diabetes in Taiwan seemed comparable to that of Western populations, but our population developed T2DM at a much lower BMI. Given that most cases belong to the "stable overweight" group, we also support using a population-based strategy for diabetes prevention instead of focusing on the high risk individuals.

Conserved molecular chaperone PrsA stimulates protective immunity against group A Streptococcus.

Group A Streptococcus (GAS) is a significant human pathogen that poses a global health concern. However, the development of a GAS vaccine has been challenging due to the multitude of diverse M-types and the risk of triggering cross-reactive immune responses. Our previous research has identified a critical role of PrsA1 and PrsA2, surface post-translational molecular chaperone proteins, in maintaining GAS proteome homeostasis and virulence traits. In this study, we aimed to further explore the potential of PrsA1 and PrsA2 as vaccine candidates for preventing GAS infection. We found that PrsA1 and PrsA2 are highly conserved among GAS isolates, demonstrating minimal amino acid variation. Antibodies specifically targeting PrsA1/A2 showed no cross-reactivity with human heart proteins and effectively enhanced neutrophil opsonophagocytic killing of various GAS serotypes. Additionally, passive transfer of PrsA1/A2-specific antibodies conferred protective immunity in infected mice. Compared to alum, immunization with CFA-adjuvanted PrsA1/A2 induced higher levels of Th1-associated IgG isotypes and complement activation and provided approximately 70% protection against invasive GAS challenge. These findings highlight the potential of PrsA1 and PrsA2 as universal vaccine candidates for the development of an effective GAS vaccine.