Interfacial hydration determines orientational and functional dimorphism of sterol-derived Raman tags in lipid-coated nanoparticles.

Lipid-coated noble metal nanoparticles (L-NPs) combine the biomimetic surface properties of a self-assembled lipid membrane with the plasmonic properties of a nanoparticle (NP) core. In this work, we investigate derivatives of cholesterol, which can be found in high concentrations in biological membranes, and other terpenoids, as tunable, synthetic platforms to functionalize L-NPs. Side chains of different length and polarity, with a terminal alkyne group as Raman label, are introduced into cholesterol and betulin frameworks. The synthesized tags are shown to coexist in two conformations in the lipid layer of the L-NPs, identified as "head-out" and "head-in" orientations, whose relative ratio is determined by their interactions with the lipid-water hydrogen-bonding network. The orientational dimorphism of the tags introduces orthogonal functionalities into the NP surface for selective targeting and plasmon-enhanced Raman sensing, which is utilized for the identification and Raman imaging of epidermal growth factor receptor-overexpressing cancer cells.

High-level expression of functional Pfu DNA polymerase recombinant protein by mimicking the enhanced green fluorescence protein gene codon usage.

Pfu DNA polymerase is a vital enzyme in PCR-related experiments. However, it is not easy to achieve high-level expression and high purity through one-step purification. This paper illustrates the method to acquire the full-length open reading frame of Pfu DNA polymerase. Without altering its amino acids, we have modified the codon usage, based on that of the enhanced green fluorescence protein (eGFP), and named it rPfu. The synthesized rPfu gene has been subcloned into the pET28a plasmid and expressed in four Escherichia coli strains without the pLysS plasmid. Three strains have expressed a high level of soluble Pfu DNA polymerase. With the aid of Ni-NTA His•Bind® resin, we could obtain high purity (>95%) soluble recombinant protein. Compared with the commercial, proofreading DNA polymerase, rPfu's bioactivity was 12,987 U/mg; that is, 88,311 U of rPfu could be obtained from 50 mL cultured E. coli. The purified rPfu was able to amplify the length of DNA fragments at least 5.5 kb. The method of increasing soluble protein's yield using the eGFP codon usage may introduce a new possibility to the expression of other soluble recombinant proteins.

Thermoelastic behavior of skin tissue induced by laser irradiation based on the generalized dual-phase lag model.

This paper analyzes the thermoelastic responses of skin tissue during laser irradiation based on a generalized dual-phase-lag (DPL) model. The method of separation of variables is utilized to obtain the analytical solutions for thermal and mechanical responses. The influences of some crucial parameters on temperature, displacement and stress evolutions are discussed, including the phase lag of heat flux, the phase lag of temperature gradient and the phase lag of laser pulse, the coupling factor between tissue and blood, the porosity of tissue, the equivalent diameter of tissue and the diameter of blood vessels. The generalized DPL bio-heat transfer model predicts different results from those by the classical DPL model and Pennes model. The equivalent diameter of tissue affects the coupling factor between tissue and blood, while the diameter of blood vessels mainly affects the porosity of tissue.

Multicenter Study of Azole-Resistant Aspergillus fumigatus Clinical Isolates, Taiwan1.

In a multicenter study, we determined a prevalence rate of 4% for azole-resistant Aspergillus fumigatus in Taiwan. Resistance emerged mainly from the environment (TR34/L98H, TR34/L98H/S297T/F495I, and TR46/Y121F/T289A mutations) but occasionally during azole treatment. A high mortality rate observed for azole-resistant aspergillosis necessitates diagnostic stewardship in healthcare and antifungal stewardship in the environment.

Rare variants in FANCA induce premature ovarian insufficiency.

Premature ovarian insufficiency (POI) is a major cause of reduced female fertility and affects approximately 1% women under 40 years of age. Recent advances emphasize the genetic heterogeneity of POI. Fanconi anemia (FA) genes, traditionally known for their essential roles in DNA repair and cytogenetic instability, have been demonstrated to be involved in meiosis and germ cell development. Here, we conducted whole-exome sequencing (WES) in 50 Han Chinese female patients with POI. Rare missense variants were identified in FANCA (Fanconi anemia complementation group A): c.1772G > A (p.R591Q) and c.3887A > G (p.E1296G). Both variants are heterozygous in the patients and very rare in the human population. In vitro functional studies further demonstrated that these two missense variants of FANCA exhibited reduced protein expression levels compared with the wild type, suggesting the partial loss of function. Moreover, mono-ubiquitination levels of FANCD2 upon mitomycin C stimulation were significantly reduced in cells overexpressing FANCA variants. Furthermore, a loss-of-function mutation of Fanca was generated in C57BL/6 mice for in vivo functional assay. Consistently, heterozygous mutated female mice (Fanca+/-) showed reduced fertility and declined numbers of follicles with aging when compared with the wild-type female mice. Collectively, our results suggest that heterozygous pathogenic variants in FANCA are implicated in non-syndromic POI in Han Chinese women, provide new insights into the molecular mechanisms of POI and highlight the contribution of FANCA variants in female subfertility.

Excess Mortality Associated With Colistin-Tigecycline Compared With Colistin-Carbapenem Combination Therapy for Extensively Drug-Resistant Acinetobacter baumannii Bacteremia: A Multicenter Prospective Observational Study.

OBJECTIVES: Since few therapeutic options exist for extensively drug resistant Acinetobacter baumannii, an emerging threat in ICUs worldwide, and comparative prospective studies of colistin-based combination therapies are lacking, our objective was to compare the outcomes of patients with extensively drug-resistant A. baumannii bacteremia, treated with colistin-carbapenem and colistin-tigecycline combinations. DESIGN: Prospective, observational, multicenter study. SETTING, PATIENTS, AND INTERVENTIONS: Adults with extensively drug-resistant A. baumannii bacteremia were prospectively followed from 2010 to 2013 at three hospitals in Taiwan. Extensively drug-resistant A. baumannii was defined as A. baumannii (genospecies 2) nonsusceptible to all drug classes except for colistin and tigecycline, and standard combination therapy as use of parenteral colistin-carbapenem or colistin-tigecycline for at least 48 hours after onset of bacteremia. MEASUREMENTS AND MAIN RESULTS: Primary outcome measure was 14-day mortality. Of the 176 episodes of extensively drug-resistant A. baumannii bacteremia evaluated, 55 patients with a median (interquartile range) age of 62 years (44-79 yr) and Sequential Organ Failure Assessment score of 9 (5-13) points received standard combination therapy: colistin-tigecycline in 29 patients and colistin-carbapenem in 26. Crude 14-day and in-hospital mortality rates for patients receiving colistin-tigecycline versus patients receiving colistin-carbapenem were 35% versus 15% (p=0.105) and 69% versus 50% (p=0.152), respectively. Breakthrough extensively drug-resistant A. baumannii bacteremia under steady state concentrations of combination therapy for colistin-tigecycline group was 18% and for colistin-carbapenem group was 0% (p=0.059). Eleven patients (20.0%) developed nephrotoxicity. After adjusting for age, sex, comorbidity, initial disease severity, loading colistin dose, polymicrobial infection, and primary infection site, excess 14-day mortality was associated with the use of colistin-tigecycline in the subgroup with tigecycline minimum inhibitory concentration greater than 2 mg/L compared with the use of colistin-carbapenem (hazard ratio, 6.93; 95% CI, 1.61-29.78; p=0.009). CONCLUSIONS: Increased 14-day mortality was associated with colistin-tigecycline therapy given tigecycline minimum inhibitory concentration greater than 2 mg/L compared with colistin-carbapenem therapy for extensively drug-resistant A. baumannii bacteremia.

A retrospective study of contributing factors for prognosis and survival length of cryptococcal meningoencephalitis in Southern part of China (1998-2013).

BACKGROUND: Cryptococcal meningoencephalitis (CM) is the most common opportunistic infection of the central nervous system (CNS). Despite this observation, there have only been a few studies analyzing clinical characteristics as well as cerebrospinal fluid (CSF), electroencephalograph (EEG), and magnetic resonance imaging (MRI) features in CM patients of all ages. METHODS: We reviewed the medical records of all patients diagnosed with cryptococcal meningoencephalitis from 1998 to 2013 in the Nanfang Hospital in China and gathered data on the underlying diseases, bird exposure history, and clinical features, including those from CSF, EEG and MRI. RESULTS: CM is more likely to infect adults younger than 60 years old. 71.3% of CM patients were male. Unlike data from other countries, we found that chronic use of corticosteroids or other immunosuppressants (17.59%) was the most frequent risk factor in CM patients rather than HIV infection (1.85%). Clear exposure with bird/ bird droppings before CM onset is obvious in a previous study in CM children. However, our study found that 4.63% CM patients had such an exposure. More importantly, patients with brain tissue damage (p = 0.021) and decreased CSF/blood glucose ratio (p = 0.008) were significantly associated with death, but only the decreased CSF/blood glucose ratio was the contributing factor of prognosis (odds ratio, 0.047; p = 0.025). Decreased CSF/blood glucose ratio was significantly related to the survival length of CM (odds ratio, 0.134; p = 0.033). CONCLUSIONS: Our study shows that CM has predilection for young male adults. The chronic use of corticosteroids or other immunosuppressants, rather than HIV infection or bird/bird droppings exposure, was the most frequent risk factor in CM patients in our study. Decreased CSF/blood glucose ratio was both an independent contributing factor to death and was significantly related to the survival length of CM patients. The more decreased the CSF/blood glucose ratio was, the worse prognosis and shorter survival length CM patients had.

Evaluation of the synergistic effect of eravacycline and tigecycline against carbapenemase-producing carbapenem-resistant Klebsiella pneumoniae.

BACKGROUND: Carbapenem-resistant Klebsiella pneumoniae (CRKP) poses a substantial healthcare challenge. This study assessed the in vitro efficacy of selected antibiotic combinations against CRKP infections. METHODS: Our research involved the evaluation of 40 clinical isolates of CRKP, with half expressing Klebsiella pneumoniae carbapenemase (KPC) and half producing Metallo-ß-lactamase (MBL), two key enzymes contributing to carbapenem resistance. We determined the minimum inhibitory concentrations (MICs) of four antibiotics: eravacycline, tigecycline, polymyxin-B, and ceftazidime/avibactam. Synergistic interactions between these antibiotic combinations were examined using checkerboard and time-kill analyses. RESULTS: We noted significant differences in the MICs of ceftazidime/avibactam between KPC and MBL isolates. Checkerboard analysis revealed appreciable synergy between combinations of tigecycline (35%) or eravacycline (40%) with polymyxin-B. The synergy rates for the combination of tigecycline or eravacycline with polymyxin-B were similar among the KPC and MBL isolates. These combinations maintained a synergy rate of 70.6% even against polymyxin-B resistant isolates. In contrast, combinations of tigecycline (5%) or eravacycline (10%) with ceftazidime/avibactam showed significantly lower synergy than combinations with polymyxin-B (P < 0.001 and P = 0.002, respectively). Among the MBL CRKP isolates, only one exhibited synergy with eravacycline or tigecycline and ceftazidime/avibactam combinations, and no synergistic activity was identified in the time-kill analysis for these combinations. The combination of eravacycline and polymyxin-B demonstrated the most promising synergy in the time-kill analysis. CONCLUSION: This study provides substantial evidence of a significant synergy when combining tigecycline or eravacycline with polymyxin-B against CRKP strains, including those producing MBL. These results highlight potential therapeutic strategies against CRKP infections.

Lipid metabolism-related long noncoding RNA RP11-817I4.1 promotes fatty acid synthesis and tumor progression in hepatocellular carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) is one of the most common types of tumors. The influence of lipid metabolism disruption on the development of HCC has been demonstrated in published studies. AIM: To establish an HCC prognostic model for lipid metabolism-related long non-coding RNAs (LMR-lncRNAs) and conduct in-depth research on the specific role of novel LMR-lncRNAs in HCC. METHODS: Correlation and differential expression analyses of The Cancer Genome Atlas data were used to identify differentially expressed LMR-lncRNAs. Quantitative real-time polymerase chain reaction analysis was used to evaluate the expression of LMR-lncRNAs. Nile red staining was employed to observe intracellular lipid levels. The interaction between RP11-817I4.1, miR-3120-3p, and ATP citrate lyase (ACLY) was validated through the performance of dual-luciferase reporter gene and RIP assays. RESULTS: Three LMR-lncRNAs (negative regulator of antiviral response, RNA transmembrane and coiled-coil domain family 1 antisense RNA 1, and RP11-817I4.1) were identified as predictive markers for HCC patients and were utilized in the construction of risk models. Additionally, proliferation, migration, and invasion were reduced by RP11-817I4.1 knockdown. An increase in lipid levels in HCC cells was significantly induced by RP11-817I4.1 through the miR-3120-3p/ACLY axis. CONCLUSION: LMR-lncRNAs have the capacity to predict the clinical characteristics and prognoses of HCC patients, and the discovery of a novel LMR-lncRNAs, RP11-817I4.1, revealed its role in promoting lipid accumulation, thereby accelerating the onset and progression of HCC.

Disulfidptosis-related lncRNA signatures assess immune microenvironment and drug sensitivity in hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is associated with a high mortality rate, where resistance to immunotherapy and chemotherapy plays a crucial role. A newly identified form of cell death called disulfidptosis shows promise, but its biological mechanism in HCC remains uncertain. In this study, a prognostic model was developed for Disulfidptosis-related long non-coding RNAs (DRLs) from 370 HCC patients sourced from TCGA-LIHC, utilizing five key features: AC026356.1, AC073254.1, PXN-AS1 expression, AC026412.3, and AC099066.2. High-risk HCC patients had lower survival, CD4+ T cell infiltration, and elevated immune checkpoint gene expression. Furthermore, based on the features of DRLs, HCC was classified into three subtypes. Notably, patients belonging to different subtypes demonstrated varying overall survival rates, immune cell infiltration patterns, and sensitivity to immune therapy. Moreover, the novel DRL AC026412.3 (HR = 40.207) emerged as the most significant prognostic factor, exhibiting high expression across all HCC cells. Elevated expression of AC026412.3 promoted HCC cell proliferation and induced resistance to gefitinib. In conclusion, we have discovered five DRLs and constructed a prognostic risk model. Our findings validate the correlation between DRL-related prognostic models, tumor subtypes, and the HCC immune microenvironment along with its implications for immunotherapy. Moreover, further investigation into the molecular mechanisms of key biomarkers like AC026412.3 in the future will contribute significantly to advancing our comprehension of HCC's pathogenesis and drug resistance mechanisms.

Marginal zone lymphoma with severe rashes: A case report.

BACKGROUND: Marginal zone lymphoma (MZL) is an indolent subtype of non-Hodgkin lymphoma (NHL), which is rare clinically with severe rashes as the initial symptom. CASE SUMMARY: This study reports a case of MZL with generalized skin rashes accompanied by pruritus and purulent discharge. First-line treatment with rituximab combined with zanubrutinib had poor effects. However, after switching to obinutuzumab combined with zanubrutinib, the case was alleviated, and the rashes disappeared. CONCLUSION: For patients with advanced stage MZL not benefiting from type I anti-CD20 monoclonal antibody (mAb) combination therapy, switching to a type II anti-CD20 mAb combination regimen may be considered. This approach may provide a new perspective in the treatment of MZL.

Risk factors for mortality after linezolid treatment of vancomycin-resistant Enterococcus bloodstream infection.

OBJECTIVES: We analyzed the risk factors affecting linezolid treatment outcome in vancomycin-resistant Enterococcus (VRE) bloodstream infection (BSI). METHODS: We conducted a multicenter observational study of patients who received linezolid 600 mg every 12 hours for VRE BSI. The primary outcome was 28-day mortality. The estimated area under the concentration-time curve and trough concentration were calculated. Multivariable logistic regression was used for the outcome analysis. RESULTS: A total of 170 patients were included: 114 (67.1%) survived and 56 (32.9%) did not. A total of 26 (18.2%) isolates showed a linezolid minimum inhibitory concentration (MIC) of ≤1 mg/l, 113 (79.0%) of 2 mg/l, and 4 (2.8%) of 4 mg/l. The univariable analysis showed that the linezolid MIC and concentration-time curve/MIC were not associated with mortality (P = 0.95 and P = 0.42, respectively). After adjusting for underlying comorbidity and disease severity, the linezolid dose per body weight (LDBW), body height, and interaction between them were independent risks for mortality. Marginal analysis showed that increasing the LDBW was protective in patients with a body height <160 cm. A trough concentration of >12.2 mg/l was a risk factor for thrombocytopenia. CONCLUSION: The LDBW and body height were interactively associated with clinical outcomes of linezolid treatment for VRE BSI.

The Combination of Daptomycin with Fosfomycin is More Effective than Daptomycin Alone in Reducing Mortality of Vancomycin-Resistant Enterococcal Bloodstream Infections: A Retrospective, Comparative Cohort Study.

INTRODUCTION: High-dose daptomycin-based combinations are recommended for vancomycin-resistant Enterococcus (VRE) bloodstream infection (BSI). Preclinical data have shown a synergistic effect of daptomycin/fosfomycin combinations against VRE. However, clinical studies comparing daptomycin monotherapy with daptomycin/fosfomycin combinations are unavailable. METHODS: An observational study of VRE-BSI was performed between 2010-2021 on patients receiving daptomycin monotherapy (≥ 8 mg/kg) or daptomycin combined with intravenous fosfomycin. Patients treated with concomitant ß-lactam combinations were excluded. The primary outcome was in-hospital mortality. Outcomes were analyzed using multivariable logistic regression and augmented inverse probability weighting (AIPW) analyses. RESULTS: Among 224 patients, 176 received daptomycin monotherapy, and 48 received fosfomycin combinations. The median daptomycin and fosfomycin doses were 9.8 mg/kg and 12 g/day, respectively. In-hospital mortality was 77.3% and 47.9% in the daptomycin monotherapy and fosfomycin combination groups (P < 0.001), respectively. Multivariable logistic regression analysis predicted lower mortality with fosfomycin combination treatment (adjusted odds ratio, 0.35; 95% confidence interval (CI), 0.17-0.73; P = 0.005). AIPW demonstrated a 17.8% reduced mortality with fosfomycin combinations (95% CI, - 30.6- - 4.9%; P = 0.007). The survival benefit was significant, especially among patients with a lower Pitt bacteremia score or fosfomycin minimum inhibitory concentration (MIC) ≤ 64 mg/l. Fosfomycin combination resulted in higher hypernatremia (10.4% vs. 2.8%, P = 0.04) and hypokalemia (33.3% vs. 15.3%, P = 0.009) compared to daptomycin monotherapy. CONCLUSION: The combination of high-dose daptomycin with fosfomycin improved the survival rate of patients with VRE-BSI compared to daptomycin alone. The benefit of the combination was most pronounced for VRE with fosfomycin MIC ≤ 64 mg/l and for patients with a low Pitt bacteremia score.

Multiple Metabolites Derived from Mushrooms and Their Beneficial Effect on Alzheimer's Diseases.

Mushrooms with edible and medicinal potential have received widespread attention because of their diverse biological functions, nutritional value, and delicious taste, which are closely related to their rich active components. To date, many bioactive substances have been identified and purified from mushrooms, including proteins, carbohydrates, phenols, and vitamins. More importantly, molecules derived from mushrooms show great potential to alleviate the pathological manifestations of Alzheimer's disease (AD), which seriously affects the health of elderly people. Compared with current therapeutic strategies aimed at symptomatic improvement, it is particularly important to identify natural products from resource-rich mushrooms that can modify the progression of AD. This review summarizes recent investigations of multiple constituents (carbohydrates, peptides, phenols, etc.) isolated from mushrooms to combat AD. In addition, the underlying molecular mechanisms of mushroom metabolites against AD are discussed. The various mechanisms involved in the antiAD activities of mushroom metabolites include antioxidant and anti-neuroinflammatory effects, apoptosis inhibition, and stimulation of neurite outgrowth, etc. This information will facilitate the application of mushroom-derived products in the treatment of AD. However, isolation of new metabolites from multiple types of mushrooms and further in vivo exploration of the molecular mechanisms underlying their antiAD effect are still required.

Agreement assessment of tigecycline susceptibilities determined by the disk diffusion and broth microdilution methods among commonly encountered resistant bacterial isolates: results from the Tigecycline In Vitro Surveillance in Taiwan (TIST) study, 2008 to 2010.

The Tigecycline In Vitro Surveillance in Taiwan (TIST) study, initiated in 2006, is a nationwide surveillance program designed to longitudinally monitor the in vitro activity of tigecycline against commonly encountered drug-resistant bacteria. This study compared the in vitro activity of tigecycline against 3,014 isolates of clinically important drug-resistant bacteria using the standard broth microdilution and disk diffusion methods. Species studied included methicillin-resistant Staphylococcus aureus (MRSA; n = 759), vancomycin-resistant Enterococcus faecium (VRE; n = 191), extended-spectrum ß-lactamase (ESBL)-producing Escherichia coli (n = 602), ESBL-producing Klebsiella pneumoniae (n = 736), and Acinetobacter baumannii (n = 726) that had been collected from patients treated between 2008 and 2010 at 20 hospitals in Taiwan. MICs and inhibition zone diameters were interpreted according to the currently recommended U.S. Food and Drug Administration (FDA) criteria and the European Committee on Antimicrobial Susceptibility Testing (EUCAST) criteria. The MIC(90) values of tigecycline against MRSA, VRE, ESBL-producing E. coli, ESBL-producing K. pneumoniae, and A. baumannii were 0.5, 0.125, 0.5, 2, and 8 µg/ml, respectively. The total error rates between the two methods using the FDA criteria were high: 38.4% for ESBL-producing K. pneumoniae and 33.8% for A. baumannii. Using the EUCAST criteria, the total error rate was also high (54.6%) for A. baumannii isolates. The total error rates between these two methods were <5% for MRSA, VRE, and ESBL-producing E. coli. For routine susceptibility testing of ESBL-producing K. pneumoniae and A. baumannii against tigecycline, the broth microdilution method should be used because of the poor correlation of results between these two methods.

Trends in susceptibility of vancomycin-resistant Enterococcus faecium to tigecycline, daptomycin, and linezolid and molecular epidemiology of the isolates: results from the Tigecycline In Vitro Surveillance in Taiwan (TIST) study, 2006 to 2010.

Among the 219 vancomycin-resistant Enterococcus faecium isolates collected in 20 Taiwanese hospitals from 2006 to 2010, all were susceptible to linezolid and daptomycin, and 98.6% were susceptible to tigecycline. There was a shift toward higher tigecycline MIC values (MIC(90)s) from 2006-2007 (0.06 µg/ml) to 2008-2010 (0.12 µg/ml). The MIC(90)s of daptomycin and linezolid remained stationary. Although pulsotypes among the isolates from the 20 hospitals varied, intrahospital spreading of several clones was identified in 13 hospitals.

Trends in the susceptibility of clinically important resistant bacteria to tigecycline: results from the Tigecycline In Vitro Surveillance in Taiwan study, 2006 to 2010.

The Tigecycline In Vitro Surveillance in Taiwan (TIST) study, a nationwide, prospective surveillance during 2006 to 2010, collected a total of 7,793 clinical isolates, including methicillin-resistant Staphylococcus aureus (MRSA) (n = 1,834), penicillin-resistant Streptococcus pneumoniae (PRSP) (n = 423), vancomycin-resistant enterococci (VRE) (n = 219), extended-spectrum ß-lactamase (ESBL)-producing Escherichia coli (n = 1,141), ESBL-producing Klebsiella pneumoniae (n = 1,330), Acinetobacter baumannii (n = 1,645), and Stenotrophomonas maltophilia (n = 903), from different specimens from 20 different hospitals in Taiwan. MICs of tigecycline were determined following the criteria of the U.S. Food and Drug Administration (FDA) and the European Committee on Antimicrobial Susceptibility Testing (EUCAST-2011). Among drug-resistant Gram-positive pathogens, all of the PRSP isolates were susceptible to tigecycline (MIC(90), 0.03 µg/ml), and only one MRSA isolate (MIC(90), 0.5 µg/ml) and three VRE isolates (MIC(90), 0.125 µg/ml) were nonsusceptible to tigecycline. Among the Gram-negative bacteria, the tigecycline susceptibility rates were 99.65% for ESBL-producing E. coli (MIC(90), 0.5 µg/ml) and 96.32% for ESBL-producing K. pneumoniae (MIC(90), 2 µg/ml) when interpreted by FDA criteria but were 98.7% and 85.8%, respectively, when interpreted by EUCAST-2011 criteria. The susceptibility rate for A. baumannii (MIC(90), 4 µg/ml) decreased from 80.9% in 2006 to 55.3% in 2009 but increased to 73.4% in 2010. A bimodal MIC distribution was found among carbapenem-susceptible A. baumannii isolates, and a unimodal MIC distribution was found among carbapenem-nonsusceptible A. baumannii isolates. In Taiwan, tigecycline continues to have excellent in vitro activity against several major clinically important drug-resistant bacteria, with the exception of A. baumannii.

[Mechanical buffering characteristics of feline paw pads].

In the long time of natural evolution, the bodies of some animals, such as feline, that live in the wild and complicate surroundings have evolved to possess outstanding buffering characteristics, which make the animals adapt to the environment perfectly. These animals generally have well-developed paw pads under their soles to play an important role in attenuating the intensity of impact when they land on the ground. Investigating the buffering characteristics of these animals' paw pads could help us to design "bionic" buffering and energy-absorption devices. In this paper, based on observations of animal jumping test, a simple mass-spring-buffer model was proposed to explore the buffering characteristics of the animals' paw pads. By analytically solving the differential equations of this model, the parameters concerned with paw pads functions were discussed and some significant results were obtained.

Minocycline Susceptibility and tetB Gene in Carbapenem-Resistant Acinetobacter baumannii in Taiwan.

Purpose: In this study, we evaluated the minocycline susceptibility rate in carbapenem-resistant Acinetobacter baumannii (CRAB) clinical strains, and the association between tetB carriage and minocycline susceptibility in CRAB. Patients and Methods: A total of 100 genetically unrelated CRAB clinical strains from bloodstream infection were randomly collected from a medical center in Taiwan. An argument for a new minocycline susceptibility breakpoint of 1 mg/L was suggested based on pharmacokinetic (PK) and pharmacodynamic (PD) studies. Strains with minocycline minimum inhibitory concentrations (MICs) of >1 mg/L were classified as PK-PD non-susceptible. TetB carriage was detected by polymerase chain reaction (PCR). Results: Fifty-five (55%) CRAB strains were susceptible to minocycline according to the Clinical and Laboratory Standards Institute (CLSI) criteria, among which 98.2% (54/55) were PK-PD non-susceptible. The minocycline MIC50/90 was 4/16 mg/L. Ninety-seven (97%) strains carried tetB. All of the tetB-positive strains and 66.7% (2/3) of the tetB-negative strains were PK-PD non-susceptible. By statistical analysis, tetB carriage was significantly correlated with PK-PD non-susceptibility (P = 0.03) and a higher minocycline MIC (P = 0.02). The sensitivity and specificity of the tetB PCR for predicting PK-PD non-susceptibility were 98% and 100%, respectively. Conclusion: At our institute, most CRAB strains were PK-PD non-susceptible and most carried tetB gene. Recognizing the minocycline MIC and tetB status may be essential when using minocycline to treat CRAB-related infections.

The combination of daptomycin with ß-lactam antibiotics is more effective than daptomycin alone for vancomycin-resistant Enterococcus faecium bloodstream infection.

BACKGROUND: The treatment options for vancomycin-resistant Enterococcus (VRE) are limited. A combination of daptomycin (DAP) and ß-lactam (BL) has been suggested; however clinical studies supporting this are lacking. METHODS: Patients with VR E. faecium bacteremia who received ≥ 8 mg/kg daptomycin for ≥ 72 h and initiated ≤ 5 days of culture collection between 2010 and 2021 were included. DAP+BL was defined as receiving BL for ≥ 24 h and within 24 h of DAP initiation. The primary endpoint was a composite clinical success (neither 14-day mortality, microbiological failure, nor change in the anti-VRE regimen). Outcomes were analyzed using multivariable logistic regression and augmented inverse probability weighting (AIPW). RESULTS: A total of 430 patients were enrolled (DAP, n = 45; DAP+BL, n = 385). Clinical success was achieved in 19 (42.2%) patients in the DAP group and 244 (63.4%) in the DAP+BL group [adjusted odds ratio, 3.19; 95% confidence interval (CI) 1.61-6.33; P = 0.001]. Marginal analysis showed that the efficacy of DAP+BL was particularly significant with DAP dose ≥ 9 mg/kg and DAP minimum inhibitory concentration (MIC) ≥ 2 mg/L. With the balance of AIPW, standardized mean clinical success rates for DAP and DAP+BL 37.3% and 63.5%, respectively. The difference between DAP+BL and DAP was of 26.2% in favor of DAP+BL (95% CI, 10.0-42.3%; P = 0.001). CONCLUSIONS: DAP+BL was associated with a significantly higher rate of compositive clinical success than DAP for treatment of VR E. faecium bacteremia. The study suggested BL in combination with high-dose DAP for VR E. faecium bacteremia treatment, especially when VRE showed a high DAP MIC.