Isolation and characterization of bacteriophages with activities against multi-drug-resistant Acinetobacter nosocomialis causing bloodstream infection in vivo.

BACKGROUND: Acinetobacter nosocomialis (A. nosocomialis) is a glucose non-fermentative, gram-negative bacillus that belongs to the Acinetobacter calcoaceticus-baumannii complex. In recent years, studies have found an increased clinical prevalence of A. nosocomialis. However, given the increasing trend of antibiotic resistance, developing new antibacterial agents is vital. Currently, research regarding bacteriophage therapy against A. nosocomialis is only limited. METHODS: Two A. nosocomialis bacteriophages, TCUAN1 and TCUAN2, were isolated from sewage. Experiments such as transmission electron microscopy (TEM), host-range analysis, and sequencing were performed to determine their biological and genomic characteristics. TCUAN2 were further subjected to in vivo experiments and their derived-endolysin were cloned and tested against their bacteria host. RESULTS: Transmission electron microscopy revealed that TCUAN1 and TCUAN2 belong to Myoviridae and Podoviridae, respectively. Both phages show a broad host spectrum and rapid adsorption efficiency. Further biological analysis showed that TCUAN2 possesses a shorter latent period and larger burst size compared to TCUAN1. Because TCUAN2 showed a better antibacterial activity, it was injected into A. nosocomialis-infected mice which resulted in a significant decrease in bacterial load levels in the blood and increased the mice's survival. Finally, genomic analysis revealed that the complete nucleotide sequence of TCUAN1 is 49, 691 bps (containing 75 open reading frames) with a G + C content of 39.3%; whereas the complete nucleotide sequence of TCUAN2 is 41, 815 bps (containing 68 open reading frames) with a G + C content of 39.1%. The endolysin gene cloned and purified from TCUAN2 also showed antibacterial activity when used with a chelator EDTA.

Salmonella typhimurium exacerbates injuries but resolves fibrosis in liver and spleen during Schistosoma mansoni infection.

BACKGROUND: In most developing or undeveloped countries, patients are often co-infected with multiple pathogens rather than a single pathogen. While different pathogens have their impact on morbidity and mortality, co-infection of more than one pathogen usually made the disease outcome different. Many studies reported the co-infection of Schistosoma with Salmonella in pandemic areas. However, the link or the underlying mechanism in the pathogenesis caused by Schistosoma-Salmonella co-infection is still unknown. METHODS: In this study, Salmonella typhimurium (S. typhimurium) was challenged to Schistosoma mansoni (S. mansoni)-infected mice. Further experiments such as bacterial culture, histopathological examination, western blotting, and flow cytometry were performed to evaluate the outcomes of the infection. Cytokine responses of the mice were also determined by ELISA and real-time quantitative PCR. RESULTS: Our results demonstrated that co-infected mice resulted in higher bacterial excretion in the acute phase but higher bacterial colonization in the chronic phase. Lesser egg burden was also observed during chronic schistosomiasis. Infection with S. typhimurium during schistosomiasis induces activation of the inflammasome and apoptosis, thereby leading to more drastic tissue damage. Interestingly, co-infected mice showed a lower fibrotic response in the liver and spleen. Further, co-infection alters the immunological functioning of the mice, possibly the reason for the observed pathological outcomes. CONCLUSION: Collectively, our findings here demonstrated that S. mansoni-infected mice challenged with S. typhimurium altered their immunological responses, thereby leading to different pathological outcomes.

Evaluating Antioxidant Performance, Biosafety, and Antimicrobial Efficacy of Houttuynia cordata Extract and Microwave-Assisted Synthesis of Biogenic Silver Nano-Antibiotics.

From the traditional Chinese medicine point of view, although Houttuynia cordata extract (HCE) possesses an incredible amount of phytonutrients and exhibits antioxidant activities, excessive doses of HCE can cause danger to organisms and lead to death. In this study, we first examine HCE's overall phenolic and flavonoid content, antioxidant efficacy, and antibacterial activity. Results show that HCE is suitable as a bio-reducing agent for the microwave-assisted synthesis of silver nanoparticles (HCE-AgNPs) with enhanced antioxidant and antimicrobial performance. Under an optimized microwave condition (i.e., 100 °C for 10 min), the HCE-stabilized AgNPs were confirmed with a UV-visible peak at 430 nm and 19.7 ± 4.2 nm in size. Physicochemical properties of HCE-AgNPs were extensively characterized by zeta-potential, FT-IR, XRD, and XPS measurements. Compared to the HC extract counterpart, HCE-AgNPs display superior antioxidant activity, higher DPPH scavenging efficiency, and enhanced broad-spectrum bactericidal activity to inhibit the growth of all tested bacterial strains at doses of 2 µg/mL. Biosafety evaluation indicated that HCE-AgNPs are noncytotoxic on human red blood cells. These data show that the microwave synthesis of AgNPs exhibits a great antioxidant ability, superior antibacterial activity, and a trivial hemolytic effect, providing another bactericidal therapy strategy to address the increasing healthcare-associated infections.

Biological and genomic characterization of two newly isolated Elizabethkingia anophelis bacteriophages.

BACKGROUND: Elizabethkingia anophelis is an opportunistic pathogen that infects newborns and immunocompromised patients. Because the infection is associated with high mortality as a result of its intrinsic resistance to antibiotics, alternative treatment methods are needed. Our previous study successfully isolated the world's first E. anophelis phage, TCUEAP1, which showed beneficial protection to E. anophelis-infected mice. More new bacteriophages are needed in order to provide sufficient choices to combat E. anophelis infections. METHODS: In the current study, two new phages infecting E. anophelis were isolated from wastewater and were designated as TCUEAP2 and TCUEAP3. Further experiments, namely, transmission electron microscopy (TEM), infection assay, host-range analysis, and sequencing were performed to determine their biological and genomic characteristics. RESULTS: TEM analysis revealed that both TCUEAP2 and TCUEAP3 possess an icosahedral head with a non-contractile tail, and belong to the Siphoviridae family. Further experiments revealed that TCUEAP3 has a longer latent period and higher burst size compared to TCUEAP2. Host range analysis showed that both TCUEAP2 and TCUEAP3 have a narrow host range, infecting only their respective hosts. The genomic size of phage TCUEAP2 was 42,403 bps containing 61 predicted open reading frames (ORFs), whereas the genome size of TCUEAP3 was 37,073 bps containing 40 predicted ORFs. CONCLUSION: Due to the distinct biological characteristics of TCUEAP2 and TCUEAP3, they may be satisfactory for clinical uses such as preparation of phage cocktails or decontamination in clinical settings.

Quantitative volumetric computed tomography embolic analysis, the Qanadli score, biomarkers, and clinical prognosis in patients with acute pulmonary embolism.

Detailed descriptions of acute pulmonary emboli (PE) morphology, total embolic volume (TEV), and their effects upon patients' clinical presentation and prognosis remain largely unexplored. We studied 201 subjects with acute PE to the emergency department of a single medical center from April 2009 to December 2014. Patient hemodynamics, Troponin I and D-dimer levels, echocardiography, and the 30-day, 90-day and long-term mortality were obtained. Contrast-enhanced computed tomography (CT) of pulmonary structures and 3-dimensional measures of embolic burden were performed. The results showed a linear association between the greater TEV and each of the following 4 variables (increasing incidence of right ventricular (RV) dysfunction, higher systolic pulmonary artery pressure (sPAP), greater RV diameter, and RV/left ventricular (LV) ratio (all p < 0.001)). Among the measures of CT and echocardiography, TEV and RV/LV ratio were significantly associated with impending shock. In backward stepwise logistic regression, TEV, age and respiratory rate remained independent associated with impending shock (OR: 1.58, 1.03, 1.18, respectively and all p < 0.005).Total embolic burden assessed by CT-based quantification serves as a useful index for stressed cardiopulmonary circulation condition and can provide insights into RV dysfunction and the prediction of impending shock.

Pulmonary vascular volume is associated with DLCO and fibrotic score in idiopathic pulmonary fibrosis: an observational study.

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a disease that primarily occurs in elderly individuals. However, it is difficult to diagnose and has a complex disease course. High-resolution computed tomography (HRCT) and lung function testing are crucial for its diagnosis and follow-up. However, the correlation of HRCT findings with lung function test results has not been extensively investigated. METHODS: This study retrospectively analysed the medical records and images of patients with IPF. Patients with evident emphysema and lung cancer were excluded. The diagnosis of all the included cases was confirmed following a discussion among specialists from multiple disciplines. The correlation of HRCT findings, including fibrotic score, HRCT lung volume, pulmonary artery trunk (PA) diameter and pulmonary vascular volume (PVV), with lung function test parameters, such as forced vital capacity (FVC) and diffusing capacity for carbon monoxide (DLCO), was analysed. RESULTS: A total of 32 patients were included. Higher fibrotic and PVV scores were significantly correlated with lower DLCO (r = - 0.59, p = 0.01; r = - 0.43, p = 0.03, respectively) but not with FVC. Higher PVV score significantly correlated with higher fibrotic score (r = 0.59, p < 0.01) and PA diameter (r = 0.47, p = 0.006). CONCLUSION: Our study demonstrated the structural and functional correlation of IPF. The extent of lung fibrosis (fibrotic score) and PVV score were associated with DLCO but not with FVC. The PA diameter, which reflects the pulmonary artery pressure, was found to be associated with the PVV score.

Radiomics for the Prediction of Response to Antifibrotic Treatment in Patients with Idiopathic Pulmonary Fibrosis: A Pilot Study.

Antifibrotic therapy has changed the treatment paradigm for idiopathic pulmonary fibrosis (IPF); however, a subset of patients still experienced rapid disease progression despite treatment. This study aimed to determine whether CT-based radiomic features can predict therapeutic response to antifibrotic agents. In this retrospective study, 35 patients with IPF on antifibrotic treatment enrolled from two centers were divided into training (n = 26) and external validation (n = 9) sets. Clinical and pulmonary function data were collected. The patients were categorized into stable disease (SD) and progressive disease (PD) groups based on functional or radiologic criteria. From pretreatment non-enhanced high-resolution CT (HRCT) images, twenty-six radiomic features were extracted through whole-lung texture analysis, and six parenchymal patterns were quantified using dedicated imaging platforms. The predictive factors for PD were determined via univariate and multivariate logistic regression analyses. In the training set (SD/PD: 12/14), univariate analysis identified eight radiomic features and ground-glass opacity percentage (GGO%) as potential predicators of PD. However, multivariate analysis found that the single independent predictor was the sum entropy (accuracy, 80.77%; AUC, 0.75). The combined sum entropy-GGO% model improved the predictive performance in the training set (accuracy, 88.46%; AUC, 0.77). The overall accuracy of the combined model in the validation set (SD/PD: 7/2) was 66.67%. Our preliminary results demonstrated that radiomic features based on pretreatment HRCT could predict the response of patients with IPF to antifibrotic treatment.

EGFR Q787Q Polymorphism Is a Germline Variant and a Prognostic Factor for Lung Cancer Treated With TKIs.

The prevalence and impact of epidermal growth factor receptor (EGFR) Q787Q polymorphism on the treatment of lung adenocarcinoma remains unclear. We retrospectively analyzed patients with stage IV lung adenocarcinoma to evaluate the prevalence of the EGFR Q787Q polymorphism and its influence on effects of tyrosine kinase inhibitor (TKI) treatment. A total of 333 patients were included in this study. The prevalence of the EGFR Q787Q polymorphism was 38%, 42%, and 35% in the total patients, EGFR mutation negative, and EGFR mutation positive groups, respectively. The prevalence of EGFR Q787Q polymorphism was significantly higher in EGFR wild-type patients than in the general non-cancerous population from Taiwan Biobank and 1000 Genome Project databases, respectively. EGFR Q787Q polymorphism had significant protective effects on the overall survival of EGFR-mutant lung adenocarcinoma treated with EGFR TKIs (aHR =0.61, p=0.03). Our study demonstrated that EGFR Q787Q polymorphism is a germline variant in the general population. It is a protective predictor of overall survival in patients with stage IV EGFR-mutated lung adenocarcinoma treated with TKIs.

Prevalence and genotypes of Cryptosporidium in livestock in Hualien Country, Eastern Taiwan.

Cryptosporidium spp. is a group of protozoans that cause diarrheal disease in both humans and animals. In Taiwan, very little information is available about the epidemiology of Cryptosporidium spp. in domesticated animals, especially in Eastern Taiwan where agriculture is one of the main industries. Therefore, this study aimed to investigate the occurrence of Cryptosporidium spp. in livestock in Hualien Country of Eastern Taiwan and identify their genotypes. Excrements from dogs (n = 81), cattle (n = 156), and pigs (n = 142) were randomly collected from different pastures or farm in Hualien Country. Microscopic examination and nested PCR were performed on all samples and both showed identical results, with 4.94% (4/81) of dogs, 24.36% (38/156) of cattle, and 16.20% (23/142) of pigs being infected with Cryptosporidium species. Positive samples were then sequenced and analyzed. DNA sequencing revealed that all four positive samples isolated from dogs were Cryptosporidium canis (C. canis); 38 positive samples from cattle were identified as C. bovis (8/38), C. canis (1/38), C. ryanae (4/38), and C. scrofarum (25/38); and 22 positive samples isolated from pigs were identified as C. scrofarum while one was identified as C. suis. In addition, the infective rates of animals from indoor farms (57.14% of all positive samples) are much higher than the rates from pastures. This study provided evidence of the occurrence of Cryptosporidium spp. in Hualien country, and farming conditions largely affect their infection rates. Therefore, precautions should be made to control Cryptosporidium spp. transmission.

Increased immunogenicity and protection of recombinant Sm14 antigens by heat-killed Cutibacterium acnes in BALB/c mice infected with Schistosoma mansoni.

After many years of the excessive use of praziquantel against Schistosoma mansoni (S. mansoni), it has already led to the development of drug resistance. While schistosomiasis is still affecting millions of people every year, vaccination may be one realistic alternative way to control the disease. Currently, S. mansoni 14-kDa fatty acid-binding protein (Sm14) has shown promising results as a vaccine antigen. Yet, the use of an adjuvant may be necessary to further increase the effectiveness of the vaccine. Herein, we investigated the potential of using heat-killed Cutibacterium acnes (C. acnes) as an adjuvant for recombinant Sm14 (rSm14). Immunization of mice with C. acnes-adjuvanted rSm14 showed increased humoral immune responses, compared with mice immunized with rSm14 alone. Additionally, C. acnes-adjuvanted rSm14 vaccination provided higher protection to mice against S. mansoni infection and liver injuries. These results suggest that C. acnes increases the immunogenicity of rSm14, which leads to better protection against S. mansoni infection. Therefore, heat-killed C. acnes may be a promising adjuvant to use with rSm14.

Quantification of Cancer-Developing Idiopathic Pulmonary Fibrosis Using Whole-Lung Texture Analysis of HRCT Images.

Idiopathic pulmonary fibrosis (IPF) patients have a significantly higher risk of developing lung cancer (LC). There is only limited evidence of the use of texture-based radiomics features from high-resolution computed tomography (HRCT) images for risk stratification of IPF patients for LC. We retrospectively enrolled subjects who suffered from IPF in this study. Clinical data including age, gender, smoking status, and pulmonary function were recorded. Non-contrast chest CT for fibrotic score calculation and determination of three dimensional measures of whole-lung texture and emphysema were performed using a promising deep learning imaging platform. The results revealed that among 116 subjects with IPF (90 non-cancer and 26 lung cancer cases), the radiomics features showed significant differences between non-cancer and cancer patients. In the training cohort, the diagnostic accuracy using selected radiomics features with AUC of 0.66-0.73 (sensitivity of 80.0-85.0% and specificity of 54.2-59.7%) was not inferior to that obtained using traditional risk factors, such as gender, smoking status, and emphysema (%). In the validation cohort, the combination of radiomics features and traditional risk factors produced a diagnostic accuracy of 0.87 AUC and an accuracy of 75.0%. In this study, we found that whole-lung CT texture analysis is a promising tool for LC risk stratification of IPF patients.

Systematic Evaluation of Antioxidant Efficiency and Antibacterial Mechanism of Bitter Gourd Extract Stabilized Silver Nanoparticles.

In this study, we accentuate the facile and green synthesis of ecologically viable silver nanoparticles (AgNPs) using aqueous (A-BGE) and ethanolic (E-BGE) dried bitter gourd (Momordica charantia) fruit extract as reducing and capping agents. Although AgNPs synthesized using BGEs have been reported earlier in fundamental antimicrobial studies, the possible antioxidant activity, antibacterial efficacy against superbugs, and a potential antimicrobial mechanism are still lacking. The characterization of as-prepared AgNPs was studied through UV-vis, TEM, Zeta-potential, FT-IR, XRD, and XPS analysis. The antioxidant ability of BG-AgNPs was extensively evaluated through DPPH and FRAP assays, which showed that A-BG-AgNPs possessed higher scavenging ability and superior reducing power due to the high phenolic content present in the BG extract. Furthermore, A-BG-AgNPs were highly stable in various physiological media and displayed excellent antibacterial activity against drug-resistant bacterial strains (i.e., MIC value of 4 µg/mL). The generation of reactive oxygen species evidenced that the possible antimicrobial mechanism was induced by BG-AgNPs, resulting in bacterial cell damage. Within the minimal hemolysis, the BG-mediated AgNPs possessed synergistic antioxidant and antibacterial agents and open another avenue for the inhibition of the growth of pathogens.

Therapeutic Effect of a Newly Isolated Lytic Bacteriophage against Multi-Drug-Resistant Cutibacterium acnes Infection in Mice.

Acne vulgaris, which is mostly associated with the colonization of Cutibacterium acnes (C. acnes), is a common skin inflammatory disease in teenagers. However, over the past few years, the disease has extended beyond childhood to chronically infect approximately 40% of adults. While antibiotics have been used for several decades to treat acne lesions, antibiotic resistance is a growing crisis; thus, finding a new therapeutic target is urgently needed. Studies have shown that phage therapy may be one alternative for treating multi-drug-resistant bacterial infections. In the present study, we successfully isolated a C. acnes phage named TCUCAP1 from the skin of healthy volunteers. Morphological analysis revealed that TCUCAP1 belongs to the family Siphoviridae with an icosahedral head and a non-contractile tail. Genome analysis found that TCUCAP1 is composed of 29,547 bp with a G+C content of 53.83% and 56 predicted open reading frames (ORFs). The ORFs were associated with phage structure, packing, host lysis, DNA metabolism, and additional functions. Phage treatments applied to mice with multi-drug-resistant (MDR) C.-acnes-induced skin inflammation resulted in a significant decrease in inflammatory lesions. In addition, our attempt to formulate the phage into hydroxyethyl cellulose (HEC) cream may provide new antibacterial preparations for human infections. Our results demonstrate that TCUCAP1 displays several features that make it an ideal candidate for the control of C. acnes infections.

Phage Digestion of a Bacterial Capsule Imparts Resistance to Two Antibiotic Agents.

Bacteriophages are viruses that infect bacteria, replicating and multiplying using host resources. For specific infections, bacteriophages have developed extraordinary proteins for recognizing and degrading their host. Inspired by the remarkable development of viral proteins, we used the tail fiber protein to treat multiple drug-resistant Acinetobacter baumannii. The tail fiber protein exhibits polysaccharide depolymerases activity which specifically degrades exopolysaccharide (EPS) during the phage-host interaction. However, EPS-degraded cells are observed altering host susceptibility to bacterial lysis peptide, the endolysin-derived peptide. Notably, endolysin is necessary in the process of progeny liberation by breaking the bacterial cell wall. Surprisingly, peeling the EPS animated host to resist colistin, the last-resort antibiotic used in multidrug-resistant Gram-negative bacteria infection. Tail fiber-modified cell wall reduces colistin attachment, causing temporary antibiotic-resistance and possibly raising clinical risks in treating multiple drug-resistant A. baumannii.

Surgical resection of brain metastases prolongs overall survival in non-small-cell lung cancer.

It remains unclear whether surgical resection of brain metastases prolongs overall survival in patients with non-small-cell lung cancer (NSCLC). A retrospective study was designed to evaluate the benefits of surgical resection for 296 patients with NSCLC and brain metastases. Patients were grouped into those who underwent craniotomy (brain surgery group) and those who did not (non-surgery group). Characteristics, survival, and EGFR mutation status were compared between the two groups. We found that the clinical characteristics were similar between the two groups. However, patients in the brain surgery group had metastases of larger diameters (3.67 cm vs. 2.06 cm, P<0.001) and a lower rate of extracranial metastasis (8.7% vs. 45.5%, P=0.001). Overall survival was significantly longer for those who underwent brain surgery (40.3 months vs. 8.4 months, P<0.001). The adjusted hazard ratio of craniotomy was 0.30 (95% confidence interval [CI], 0.15-0.62). The survival benefit of brain surgery was observed in both EGFR mutation-positive and EGFR mutation-negative sub-populations; the adjusted hazard ratios [aHRs] were 0.34 [95% CI, 0.11-1.00] and 0.26 [95% CI, 0.09-0.73] for EGFR mutation-positive and mutation-negative sub-populations, respectively. We concluded that for patients with NSCLC and brain metastases, surgical resection of brain metastases improved overall survival. This survival benefit was particularly evident in cases with large-sized metastases limited to the brain.

Mitochondrial dynamics in Angiostrongylus cantonensis-infected mouse brain.

Angiostrongylus cantonensis is one of the most widespread parasites causing central nervous system (CNS) diseases in mammals. Since the mitochondrion is an essential cell organelle responsible for both physiological and pathological processes, its dysfunction might lead to inflammation and multiple disorders. In this study we aimed to investigate the changes in mitochondrial dynamics that occur in the mouse brain upon infection with A. cantonensis, using molecular biology techniques such as polymerase chain reaction (PCR), western blot analysis, transmission electron microscopy (TEM), and different staining methods. Here, we show that mouse brain infected with A. cantonensis exhibits altered mitochondrial dynamics, including fission, fusion, and biogenesis. Additionally, we demonstrate that caspases and B-cell lymphoma 2 (BCL-2) were significantly upregulated in A. cantonensis-infected brain. These results are indicative of the occurrence of apoptosis during A. cantonensis infection, which was further confirmed by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining. These findings suggest the change in mitochondrial dynamics in A. cantonensis-infected brain, providing another point of view on the pathogenesis of meningoencephalitis caused by A. cantonensis infection.

Isolation and Characterization of a New Phage Infecting Elizabethkingia anophelis and Evaluation of Its Therapeutic Efficacy in vitro and in vivo.

Elizabethkingia spp. are a group of non-fermentative, Gram-negative, catalase-positive, and non-motile bacilli. They can cause meningitis in neonates and immunosuppressed patients, and lead to high mortality. Considering the rising trend of drug resistance among bacteria pathogens, bacteriophage (phage) therapy is a potential alternative to antibiotics for treating multidrug-resistant bacterial infections. However, so far, no phages specific for Elizabethkingia spp. have been reported. Using a clinically isolated Elizabethkingia anophelis as the host, the phage TCUEAP1 was isolated from wastewater of Hualien Tzu Chi hospital. The phage particle of TCUEAP1 under electron microscopy was revealed to belong to the siphoviridae family, with a head size of 47 nm, and a tail dimension 12 nm in diameter and 172 nm in length. The one-step growth analysis showed that the latent period of TCUEAP1 was about 40 min with a rise period lasting about 20 min, yielding a burst size of approximately 10 PFU/cell. The adsorption rate of TCUEAP1 reached about 70% in 20 min. Using 20 isolates of Elizabethkingia spp. to test the host range of TCUEAP1, it displayed narrow spectrum infecting three strains of E. anophelis, but forming spot lysis on 16 strains. The sequence result showed that the genome of TCUEAP1 is a double-stranded DNA of 49,816 bp, containing 73 predicted open reading frames. Further genomic analysis showed TCUEAP1 to be a new phage with no resemblance to publicly available phage genomes. Finally, in a mouse intraperitoneal infection model, at 6 h after the bacterial injection, TCUEAP1 decreased the bacterial load by fivefold in blood. Also, TCUEAP1 rescued 80% of mice heavily infected with E. anophelis from lethal bacteremia. We hope that the isolation and characterization of TCUEAP1, the first phage infecting Elizabethkingia spp., can promote more studies of the phages targeting this newly emerging bacterial pathogen.

Design and Study of a Portable High-frequency Ventilator for Clinical Applications.

Treatment costs for ventilator-dependent patients are a substantial burden not only for their family but also for medical systems in general. Recently, using high-frequency ventilators have been shown to reduce the risk of lung injury through low-volume airflow. However, the machines used today remain bulky, costly, and only for use in hospital settings. To provide intermediate therapy for patients between hospitalization and complete discharge, a portable, light-weight high-frequency ventilator is an urgent need. This work presents the design of a portable high-frequency ventilator and a study of its practicality for further clinical medical applications. Through the integration of advanced electronics and mechanical instruments, we develop a portable high-frequency ventilator with reconfigurable oxygen flow rate, applied pressure, and air volume for the needs of individual patients. A miniaturized portable high-frequency ventilator with digital controller and feedback system for stabilization and precision control is implemented. The efficiency of CO2 washout using the proposed ventilator has been demonstrated in animal trials.

Novel 10-Bit Impedance-to-Digital Converter for Electrochemical Impedance Spectroscopy Measurements.

Electrochemical impedance spectroscopy (EIS) is a widely used technique in biomedical and chemical analysis. A novel 10-bit impedance-to-digital converter (IDC), which can measure and directly convert the magnitude and phase of impedance to digital codes, is proposed for the EIS measurement system. The proposed IDC is composed of a magnitude-to-digital converter (MDC) and a phase-to-digital converter (PDC). The proposed IDC was designed and fabricated using a 0.35 [Formula: see text] 2P4M mixed-signal polycide process, and the core area is only 0.07 mm2. Moreover, it can work over a very wide frequency range (0.1 mHz-100 kHz), and has excellent accuracy. According to the measured results, the DNL of the MDC is within -0.3/+0.3 LSB, and the INL is around -3/+1 LSB. Moreover, an EIS measurement system, which is composed of the proposed IDC chip and some other commercial chips, is built to measure ZoBell's and melatonin solutions for validating the function of the proposed IDC.

Clonal spread of multidrug-resistant Acinetobacter baumannii in eastern Taiwan.

BACKGROUND AND PURPOSE: This study was conducted to investigate the molecular epidemiology and antimicrobial susceptibility of multidrug-resistant (MDR) Acinetobacter baumannii to three types of antibiotics. METHODS: One hundred and thirty-four specimens of MDR A baumannii were collected from three branches (Taipei, Dalin, and Hualien branches) of Buddhist Tzu Chi Hospital, which are located in northern, southern, and eastern Taiwan, during 2007. Genotyping was performed by pulsed-field gel electrophoresis. Antibiotic susceptibilities to colistin, rifampicin, and tigecycline were determined. The synergistic effects of rifampin and colistin were also evaluated. RESULTS: Antibiotic susceptibility testing showed that 10.4%, 47.8% and 45.5% of the MDR A baumannii isolates are resistant to colistin, rifampicin, and tigecycline, respectively. A majority of the rifampicin-resistant isolates (62.7%) were found in the Haulien branch, whereas 62.2% of tigecycline-resistant isolates were found in the Taipei branch. The combination of colistin and rifampicin had a synergistic effect on all of the isolates. Genotyping by pulsed-field gel electrophoresis identified 17, 23, and 11 pulsotypes in the Taipei, Dalin, and Haulien branches, respectively. Furthermore, 74.5% of isolates in the Haulien branch were identified as one of three pulsotypes. Among 37 rifampicin-resistant and 22 tigecycline-resistant MDR A baumannii isolates found in the Haulien branch, 51.3% (19/37) and 50% (11/22) of the isolates belonged to the same clone, respectively. CONCLUSION: This study confirms the high prevalence of resistance to rifampicin and tigecycline in MDR A baumannii in the three hospitals that were studied, and the high proportion of identical strains that exist in eastern Taiwan.