Large-area and few-layered 1T'-MoTe2 thin films grown by cold-wall chemical vapor deposition.

This study employs cold-wall chemical vapor deposition to achieve the growth of MoTe2thin films on 4-inch sapphire substrates. A two-step growth process is utilized, incorporating MoO3and Te powder sources under low-pressure conditions to synthesize MoTe2. The resultant MoTe2thin films exhibit a dominant 1T' phase, as evidenced by a prominent Raman peak at 161 cm-1. This preferential 1T' phase formation is attributed to controlled manipulation of the second-step growth temperature, essentially the reaction stage between Te vapor and the pre-deposited MoOx layer. Under these optimized growth conditions, the thickness of the continuous 1T'-MoTe2films can be precisely tailored within the range of 3.5 - 5.7 nm (equivalent to 5 - 8 layers), as determined by atomic force microscopy depth profiling. Hall-effect measurements unveil a typical hole concentration and mobility of 0.2 cm2/V-s and 7.9 × 1021cm-3, respectively, for the synthesized few-layered 1T'-MoTe2 films. Furthermore, Ti/Al bilayer metal contacts deposited on the few-layered 1T'-MoTe2films exhibit low specific contact resistances of approximately 1.0 × 10-4Ω-cm2estimated by the transfer length model. This finding suggests a viable approach for achieving low ohmic contact resistance using the 1T'-MoTe2intermediate layer between metallic electrodes and two-dimensional semiconductors.

Resistance-proof antimicrobial drug discovery to combat global antimicrobial resistance threat.

Drug resistance is well-defined as a serious problem in our living world. To survive, microbes develop defense strategies against antimicrobial drugs. Drugs exhibit less or no effective results against microbes after the emergence of resistance because they are unable to cross the microbial membrane, in order to alter enzymatic systems, and/or upregulate efflux pumps, etc. Drug resistance issues can be addressed effectively if a "Resistance-Proof" or "Resistance-Resistant" antimicrobial agent is developed. This article discusses first the need for resistance-proof drugs, the imminent properties of resistance-proof drugs, current and future research progress in the discovery of resistance-proof antimicrobials, the inherent challenges, and opportunities. A molecule having imminent resistance-proof properties could target microbes efficiently, increase potency, and rule out the possibility of early resistance. This review triggers the scientific community to think about how an upsurge in drug resistance can be averted and emphasizes the discussion on the development of next-generation antimicrobials that will provide a novel effective solution to combat the global problem of drug resistance. Hence, resistance-proof drug development is not just a requirement but rather a compulsion in the drug discovery field so that resistance can be battled effectively. We discuss several properties of resistance-proof drugs which could initiate new ways of thinking about next-generation antimicrobials to resolve the drug resistance problem. This article sheds light on the issues of drug resistance and discusses solutions in terms of the resistance-proof properties of a molecule. In summary, the article is a foundation to break new ground in the development of resistance-proof therapeutics in the field of infection biology.

Targeted HAI-2 deletion causes excessive proteolysis with prolonged active prostasin and depletion of HAI-1 monomer in intestinal but not epidermal epithelial cells.

Mutations of SPINT2, the gene encoding the integral membrane, Kunitz-type serine inhibitor HAI-2, primarily affect the intestine, while sparing many other HAI-2-expressing tissues, causing sodium loss in patients with syndromic congenital sodium diarrhea. The membrane-bound serine protease prostasin was previously identified as a HAI-2 target protease in intestinal tissues but not in the skin. In both tissues, the highly related inhibitor HAI-1 is, however, the default inhibitor for prostasin and the type 2 transmembrane serine protease matriptase. This cell-type selective functional linkage may contribute to the organ-selective damage associated with SPINT 2 mutations. To this end, the impact of HAI-2 deletion on matriptase and prostasin proteolysis was, here, compared using Caco-2 human colorectal adenocarcinoma cells and HaCaT human keratinocytes. Greatly enhanced prostasin proteolytic activity with a prolonged half-life and significant depletion of HAI-1 monomer were observed with HAI-2 loss in Caco-2 cells but not HaCaT cells. The constitutive, high level prostasin zymogen activation observed in Caco-2 cells, but not in HaCaT cells, also contributes to the excessive prostasin proteolytic activity caused by HAI-2 loss. HAI-2 deletion also caused increased matriptase zymogen activation, likely as an indirect result of increased prostasin proteolysis. This increase in activated matriptase, however, only had a negligible role in depletion of HAI-1 monomer. Our study suggests that the constitutive, high level of prostasin zymogen activation and the cell-type selective functional relationship between HAI-2 and prostasin renders Caco-2 cells more susceptible than HaCaT cells to the loss of HAI-2, causing a severe imbalance favoring prostasin proteolysis.

Case Report: Multiple Sclerosis Presenting as Unilateral Gaze-evoked Nystagmus.

SIGNIFICANCE: Unilateral gaze-evoked nystagmus is a rare neurologic finding that is largely diagnosed in connection with ischemic stroke. Gazed-evoked nystagmus is also a rare initial presentation of multiple sclerosis. PURPOSE: This study aimed to report a rare presentation of gaze-evoked nystagmus in a patient with multiple sclerosis and review the mechanism underlying the gaze-evoked nystagmus. CASE REPORT: A 32-year-old man presented with a 1-week history of diplopia. Neurologic examination revealed right-sided gaze-evoked nystagmus and right-sided ataxia. Laboratory test revealed a positive result for oligoclonal bands. Contrast brain MRI revealed multiple hyperintense T2 lesions including a hyperintense patch at the right inferior cerebellar peduncle. A diagnosis of multiple sclerosis was made. The patient received methylprednisolone 500 mg intravenously for 14 days. The diplopia and gaze-evoked nystagmus resolved and remained stable 2 months later. CONCLUSIONS: Our case demonstrates that damage to the inferior cerebellar peduncle may result in ipsilesional gaze-evoked nystagmus and ipsilesional ataxia, in contrast to ipsilesional gaze-evoked nystagmus and contralesional ataxia.

Design of Edge-IoMT Network Architecture with Weight-Based Scheduling.

Population health monitoring based on the Internet of Medical Things (IoMT) is becoming an important application trend healthcare improvement. This work aims to develop an autonomous network architecture, collecting sensor data with a cluster topology, forwarding information through relay nodes, and applying edge computing and transmission scheduling for network scalability and operational efficiency. The proposed distributed network architecture incorporates data compression technologies and effective scheduling algorithms for handling the transmission scheduling of various physiological signals. Compared to existing scheduling mechanisms, the experimental results depict the network performance and show that in analyzing the delay and jitter, the proposed WFQ-based algorithms have reduced the delay and jitter ratio by about 40% and 19.47% compared to LLQ with priority queueing scheme, respectively. The experimental results also demonstrate that the proposed network topology is more effective than the direct path transmission approach in terms of energy consumption, which suggests that the proposed network architecture may improve the development of medical applications with body area networks such that the goal of self-organizing population health monitoring can be achieved.

Artificial intelligence for prediction of COVID-19 progression using CT imaging and clinical data.

OBJECTIVES: Early recognition of coronavirus disease 2019 (COVID-19) severity can guide patient management. However, it is challenging to predict when COVID-19 patients will progress to critical illness. This study aimed to develop an artificial intelligence system to predict future deterioration to critical illness in COVID-19 patients. METHODS: An artificial intelligence (AI) system in a time-to-event analysis framework was developed to integrate chest CT and clinical data for risk prediction of future deterioration to critical illness in patients with COVID-19. RESULTS: A multi-institutional international cohort of 1,051 patients with RT-PCR confirmed COVID-19 and chest CT was included in this study. Of them, 282 patients developed critical illness, which was defined as requiring ICU admission and/or mechanical ventilation and/or reaching death during their hospital stay. The AI system achieved a C-index of 0.80 for predicting individual COVID-19 patients' to critical illness. The AI system successfully stratified the patients into high-risk and low-risk groups with distinct progression risks (p < 0.0001). CONCLUSIONS: Using CT imaging and clinical data, the AI system successfully predicted time to critical illness for individual patients and identified patients with high risk. AI has the potential to accurately triage patients and facilitate personalized treatment. KEY POINT: • AI system can predict time to critical illness for patients with COVID-19 by using CT imaging and clinical data.

The combination of lactate level, lactate clearance and APACHE II score better predicts short-term outcomes in critically Ill patients: a retrospective cohort study.

BACKGROUND: The mortality rate is high in critically ill patients due to the difficulty of diagnosis and treatment. Thus, it is very important to explore the predictive value of different indicators related to prognosis in critically ill patients. METHODS: This was a retrospective cohort study of patients in the intensive care unit (ICU) of the Sixth People's Hospital in Shanghai, China. A total of 1465 ICU patients had lactate values > 2.1 mmol/L at least once within 24 h of ICU admission, and arterial blood gas was monitored more than twice during the ICU stay. RESULTS: The predictive value of lactate clearance at 24 h was not high, and the sensitivity and specificity were lower. The predictive value of the lactate level at baseline and the APACHE II score was higher than that of lactate clearance at 24 h in critically ill patients. The predictive value of the lactate level at baseline combined with the APACHE II score was higher than that of the lactate level at baseline or the APACHE II score alone. In addition, the predictive value of lactate clearance at 24 h combined with the APACHE II score was also significantly higher than that of lactate clearance at 24 h or the APACHE II score alone. In particular, the area under the ROC curve reached 0.900, the predictive value was markedly higher than that of the ROC alone, and the sensitivity and specificity were better when these three indicators were combined. CONCLUSIONS: The combination of lactate level, lactate clearance and APACHE II score better predicts short-term outcomes in critically ill patients.

Artificial Intelligence Augmentation of Radiologist Performance in Distinguishing COVID-19 from Pneumonia of Other Origin at Chest CT.

Background Coronavirus disease 2019 (COVID-19) and pneumonia of other diseases share similar CT characteristics, which contributes to the challenges in differentiating them with high accuracy. Purpose To establish and evaluate an artificial intelligence (AI) system for differentiating COVID-19 and other pneumonia at chest CT and assessing radiologist performance without and with AI assistance. Materials and Methods A total of 521 patients with positive reverse transcription polymerase chain reaction results for COVID-19 and abnormal chest CT findings were retrospectively identified from 10 hospitals from January 2020 to April 2020. A total of 665 patients with non-COVID-19 pneumonia and definite evidence of pneumonia at chest CT were retrospectively selected from three hospitals between 2017 and 2019. To classify COVID-19 versus other pneumonia for each patient, abnormal CT slices were input into the EfficientNet B4 deep neural network architecture after lung segmentation, followed by a two-layer fully connected neural network to pool slices together. The final cohort of 1186 patients (132 583 CT slices) was divided into training, validation, and test sets in a 7:2:1 and equal ratio. Independent testing was performed by evaluating model performance in separate hospitals. Studies were blindly reviewed by six radiologists without and then with AI assistance. Results The final model achieved a test accuracy of 96% (95% confidence interval [CI]: 90%, 98%), a sensitivity of 95% (95% CI: 83%, 100%), and a specificity of 96% (95% CI: 88%, 99%) with area under the receiver operating characteristic curve of 0.95 and area under the precision-recall curve of 0.90. On independent testing, this model achieved an accuracy of 87% (95% CI: 82%, 90%), a sensitivity of 89% (95% CI: 81%, 94%), and a specificity of 86% (95% CI: 80%, 90%) with area under the receiver operating characteristic curve of 0.90 and area under the precision-recall curve of 0.87. Assisted by the probabilities of the model, the radiologists achieved a higher average test accuracy (90% vs 85%, Δ = 5, P < .001), sensitivity (88% vs 79%, Δ = 9, P < .001), and specificity (91% vs 88%, Δ = 3, P = .001). Conclusion Artificial intelligence assistance improved radiologists' performance in distinguishing coronavirus disease 2019 pneumonia from non-coronavirus disease 2019 pneumonia at chest CT. © RSNA, 2020 Online supplemental material is available for this article.

Performance of Radiologists in Differentiating COVID-19 from Non-COVID-19 Viral Pneumonia at Chest CT.

Background Despite its high sensitivity in diagnosing coronavirus disease 2019 (COVID-19) in a screening population, the chest CT appearance of COVID-19 pneumonia is thought to be nonspecific. Purpose To assess the performance of radiologists in the United States and China in differentiating COVID-19 from viral pneumonia at chest CT. Materials and Methods In this study, 219 patients with positive COVID-19, as determined with reverse-transcription polymerase chain reaction (RT-PCR) and abnormal chest CT findings, were retrospectively identified from seven Chinese hospitals in Hunan Province, China, from January 6 to February 20, 2020. Two hundred five patients with positive respiratory pathogen panel results for viral pneumonia and CT findings consistent with or highly suspicious for pneumonia, according to original radiologic interpretation within 7 days of each other, were identified from Rhode Island Hospital in Providence, RI. Three radiologists from China reviewed all chest CT scans (n = 424) blinded to RT-PCR findings to differentiate COVID-19 from viral pneumonia. A sample of 58 age-matched patients was randomly selected and evaluated by four radiologists from the United States in a similar fashion. Different CT features were recorded and compared between the two groups. Results For all chest CT scans (n = 424), the accuracy of the three radiologists from China in differentiating COVID-19 from non-COVID-19 viral pneumonia was 83% (350 of 424), 80% (338 of 424), and 60% (255 of 424). In the randomly selected sample (n = 58), the sensitivities of three radiologists from China and four radiologists from the United States were 80%, 67%, 97%, 93%, 83%, 73%, and 70%, respectively. The corresponding specificities of the same readers were 100%, 93%, 7%, 100%, 93%, 93%, and 100%, respectively. Compared with non-COVID-19 pneumonia, COVID-19 pneumonia was more likely to have a peripheral distribution (80% vs 57%, P < .001), ground-glass opacity (91% vs 68%, P < .001), fine reticular opacity (56% vs 22%, P < .001), and vascular thickening (59% vs 22%, P < .001), but it was less likely to have a central and peripheral distribution (14% vs 35%, P < .001), pleural effusion (4% vs 39%, P < .001), or lymphadenopathy (3% vs 10%, P = .002). Conclusion Radiologists in China and in the United States distinguished coronavirus disease 2019 from viral pneumonia at chest CT with moderate to high accuracy. © RSNA, 2020 Online supplemental material is available for this article. A translation of this abstract in Farsi is available in the supplement. ترجمه چکیده این مقاله به فارسی، در ضمیمه موجود است.

Trends in microbial profile of burn patients following an event of dust explosion at a tertiary medical center.

BACKGROUND: Microbial infection is the main cause of increased morbidity and mortality in burn patients, especially infections caused by multiple drug-resistant organisms (MDRO). The purpose of this study was to explore major microbial trends in burn patients. METHODS: This retrospective study was conducted at burn wards and intensive care units, where burn patients were admitted following an event of dust explosion. Data were collected for a number of variables including severity of burns, demographic and clinical characteristics, laboratory data, and therapeutic devices. RESULTS: A total of 1132 specimens were collected from 37 hospitalized burn patients with mean TBSA of 46.1%.The most commonly isolated species were Staphylococcus spp. (22.4%). The highest rate of antibiotic resistance was observed in carbapenem-resistant A. baumannii (14.6%), followed by methicillin-resistant S. aureus (11.3%). For each additional 10% TBSA, the isolation of MDRO increased 2.58-17.57 times (p < 0.05); for each additional 10% of the third-degree burn severity, the risk of MDRO significantly decreased by 47% (95% CI, 0.38-0.73, p < 0.001) by Cox model. CONCLUSIONS: The proportion of overall microbial isolates increased with the increase in TBSA and duration of time after burns. The extent of TBSA was the most important factor affecting MDRO.

[Preparation and evaluation of schisandrin B-loaded F127 modified lipid-polymer nanoparticles for inhibition of breast cancer lung metastasis].

In the current study, schisandrin B(SchB)-loaded F127 modified lipid-polymer hybrid nanoparticles(SchB-F-LPNs) were developed to improve the inhibition of breast cancer lung metastasis. Modified nanoprecipitation method was used to prepare SchB-F-LPNs. The nanoparticles were spherical in shape with shell-core structure by TEM observation. SchB-F-LPNs showed a mean particle size of(234.60±6.11) nm with zeta potential of(-5.88±0.49) mV. XRD results indicated that SchB existed in the nanoparticles in an amorphous state. The apparent permeability coefficient through porcine mucus of F-LPNs was 1.43-fold of that of LPNs as shown in the in vitro mucus penetration study. The pharmacokinetics study showed that the C_(max) of SchB was(369.06±146.94) µg·L~(-1),(1 121.34±91.65) µg·L~(-1) and(2 951.91±360.53) µg·L~(-1) respectively in SchB suspensions group, SchB-LPNs group and SchB-F-LPNs group after oral administration in rats. With SchB suspensions as the reference formulation, the relative bioavailability of SchB-F-LPNs was 568.60%. SchB-F-LPNs inhibited the morphological change during transforming growth factor-ß1(TGF-ß1)-induced epithelial-mesenchymal transition. In addition, SchB-F-LPNs significantly decreased the number of metastatic pulmonary nodules in 4 T1 tumor-bearing mice, suggesting that SchB-F-LPNs may inhibit the metastasis of breast cancer. These results reveal the promising potential of SchB-F-LPNs in treatment of breast cancer lung metastasis.

Immunometabolism features of metabolic deregulation and cancer.

Immunometabolism is a branch dealing at the interface of immune functionalities and metabolic regulations. Considered as a bidirectional trafficking, metabolic contents and their precursors bring a considerable change in immune cells signal transductions which as a result affect the metabolic organs and states as an implication. Lipid metabolic ingredients form a major chunk of daily diet and have a proven contribution in immune cells induction, which then undergo metabolic pathway shuffling inside their ownself. Lipid metabolic states activate relevant metabolic pathways inside immune cells that in turn prime appropriate responses to outside environment in various states including lipid metabolic disorders itself and cancers as an extension. Although data on Immunometabolism are still growing, but scientific community need to adjust and readjust according to recent data on given subject. This review attempts to provide current important data on Immunometabolism and consequently its metabolic ramifications. Incumbent data on various lipid metabolic deregulations like obesity, metabolic syndrome, obese asthma and atherosclerosis are analysed. Further, metabolic repercussions on cancers and its immune modalities are also analysed.

Activating Mas receptor protects human pulmonary microvascular endothelial cells against LPS-induced apoptosis via the NF-kB p65/P53 feedback pathways.

The balance between Ang II/AT1R and Ang-(1-7)/Mas plays a pivotal role in the development of lipopolysaccharides (LPS)-induced acute respiratory distress syndrome. However, the mechanisms underlying the balancing process still remain unclear. Here we investigated the roles of nuclear factor (NF)-κB and p53 in regulating AT1R and Mas expression. The results demonstrated that Ang II pretreatment resulted in downregulation of Mas and upregulation of AT1R, phosphorylated p65, and apoptosis in LPS-treated Human pulmonary microvascular endothelial cells (HPMVECs), but had no effect on p53 expression. Lentiviral vector-mediated P65 knockdown, but not a P53 knockdown, reversed all these effects of Ang II. On the other hand, Ang-(1-7) pretreatment lead to an increased in Mas expression and a decrease in AT1R, p53, and phosphorylated p65 expressions with suppressed apoptosis in LPS-treated cells. P65 knockdown promoted the protein expression of both AT1R and Mas while inhibiting p53 expression. P53 knockdown, but not a p65 knockdown, reversed all these effects of Ang-(1-7). Interestingly, p65 overexpression upregulated p53 and AT1R but downregulated Mas. P53 knockdown activated p65. These results suggest that there is a two-way feedback regulation between AT1R and Mas receptor via the NF-kB p65/P53 pathway, which may play a key role in LPS-induced HPMVECs apoptosis.

Ang-(1-7) treatment attenuates lipopolysaccharide-induced early pulmonary fibrosis.

Early pulmonary fibrosis is the leading cause of poor prognosis in patients with acute respiratory distress syndrome (ARDS). However, whether the renin-angiotensin system (RAS) can serve as a therapeutic target is unknown. In this study, an animal model of early pulmonary fibrosis was established via the LPS three-hit regimen. Afterwards, the animals were treated with intraperitoneal injections of Ang-(1-7), AVE0991, or A779 once per day for 20 days. The plasma and BALF AngII levels of the animals were increased, while there were no significant changes in Ang-(1-7) levels in lung tissue after LPS treatment. Furthermore, the AT1R protein levels were significantly increased and the Mas levels were significantly decreased on days 14 and 21. Administration of Ang-(1-7) downregulated LPS-induced AT1R mRNA expression, which was upregulated by A779. The expression of Mas mRNA responded in the opposite direction relative to AT1R. Moreover, LPS caused decreased levels of Mas and E-cadherin and increased AT1R, Vimentin, and Src phosphorylation levels. Ang-(1-7) or AVE0991 blocked these effects but was counteracted by A779 treatment. Our findings suggested that AngII and AT1R levels exhibit opposite dynamic trends during LPS-induced early pulmonary fibrosis, as do Ang-(1-7) and Mas. Ang-(1-7) exerts protective effects against early pulmonary fibrosis, mainly by regulating the balance between AngII and AT1R and between Ang-(1-7) and Mas and by inhibiting Src kinase activation.

The convenient Michael addition of imidazoles to acrylates catalyzed by Lipozyme TL IM from Thermomyces lanuginosus in a continuous flow microreactor.

A fast and green protocol for the Michael addition of imidazoles to acrylates catalyzed by Lipozyme TL IM from Thermomyces lanuginosus in a continuous flow microreactor was developed. In contrast with existing methods, this method is simple (35 min), uses mild reaction conditions (45 °C) and is environmentally friendly. This enzymatic Michael addition performed in continuous flow microreactors is an innovation that may open up the use of enzymatic microreactors in imidazole analogue biotransformations.

miR-200b/c attenuates lipopolysaccharide-induced early pulmonary fibrosis by targeting ZEB1/2 via p38 MAPK and TGF-ß/smad3 signaling pathways.

Pulmonary fibrosis triggered during the early stage of acute respiratory distress syndrome (ARDS) contributes to poor prognosis in patients. However, whether microRNAs (miRNAs) can serve as therapeutic targets for early pulmonary fibrosis during ARDS is still largely unknown. In this study, we evaluated the effects and mechanisms of miR-200s and its targets ZEB1/2 in lung tissue. An early pulmonary fibrosis mouse model caused by ARDS was established via a lipopolysaccharide (LPS) three-hit regimen. Lentiviral packaged miR-200b/c cDNA or ZEB1/2 shRNA was intratracheally administered into the lungs of C57BL/6 mice 1 day before an LPS injection was administered. In vitro, following a 30-min pretreatment with miR-200b/c or SB203580/SIS3, RLE-6TN cells were stimulated by LPS or LPS + transforming growth factor-ß (TGF-ß) for 24 h. miR-200b/c and E-cadherin protein expression declined, whereas ZEB1/2 mRNA and protein and vimentin and α-smooth muscle actin (α-SMA) protein levels gradually increased during the development of pulmonary fibrosis. Furthermore, both the overexpression of miR-200b/c and the silencing of ZEB1/2 significantly alleviated pulmonary inflammation and fibrosis, reduced vimentin and α-SMA expression, and increased E-cadherin protein levels. In RLE-6TN cells, LPS combined with TGF-ß exerts synergistic effects of increasing vimentin and α-SMA protein levels, increasing p38 and smad3 phosphorylation and reducing E-cadherin protein levels, which were reversed by pretreatment with miR-200b/c or SB203580/SIS3. Our findings demonstrate that miR-200b/c was downregulated, whereas ZEB1/2 was upregulated in the development of LPS-induced early pulmonary fibrosis. miR-200b/c exerts a protective effect by targeting ZEB1/2, which may be associated with the inhibition of p38 MAPK and TGF-ß /smad3 signaling pathways.

Is fluoroquinolone monotherapy a useful alternative treatment for Pseudomonas aeruginosa bacteraemia?

PURPOSE: Pseudomonas aeruginosa bacteraemia is associated with high mortality, and most monotherapies are beta-lactam-based. We aimed to investigate clinical outcomes of definitive fluoroquinolone monotherapy versus beta-lactam monotherapy for P. aeruginosa bacteraemia. METHODS: This retrospective study enrolled adult patients receiving definitive monotherapy with beta-lactam or fluoroquinolone between November 2013 and November 2014 at Taipei Veterans General Hospital. The independent risk factors for 28-day mortality were analyzed by logistic regression and propensity score-adjusted analysis. RESULTS: Among the 105 patients enrolled, 78 patients received beta-lactams and 27 received fluoroquinolones (20 with ciprofloxacin and 7 with levofloxacin). Primary bacteraemia (39.0%) and urinary tract infections (37.1%) were the most common sources of bacteraemia. The 28-day mortality rate was 11.1% for those receiving fluoroquinolones and 32.1% for those receiving beta-lactams (P = 0.062). The 28-day mortality rate between the two groups stratified by APACHE II and Pitt bacteraemia scores showed no significant differences in each category. Propensity score-adjusted multivariate analysis revealed that definitive therapy with a fluoroquinolone was not associated with 28-day mortality (OR 0.42; 95% CI 0.08-2.23; P = 0.305). CONCLUSIONS: Fluoroquinolone might be an alternative to beta-lactam as a definitive monotherapy for P. aeruginosa bacteraemia provided they are active in vitro. Our results could be a basis for further studies and provide a possible target for antibiotic stewardship interventions in P. aeruginosa bacteraemia.

Anaerobic coverage as definitive therapy does not affect clinical outcomes in community-onset bacteremic biliary tract infection without anaerobic bacteremia.

BACKGROUND: Antibiotics with anaerobic coverage are widely used for the treatment of biliary tract infection (BTI), even in the absence of isolated anaerobes. The current study aimed to investigate the differences in clinical outcomes in patients with community-onset bacteremic BTIs without anaerobic bacteremia, treated with vs. without anti-anaerobic coverage. METHODS: A retrospective analysis was conducted at a medical center in Taiwan from September 2014 to March 2016. Patients with community-onset bacteremic BTIs without anaerobic bacteremia and who were treated with appropriate antibiotics were analyzed. The clinical outcomes were compared between patients treated with and without anti-anaerobic coverage as definitive therapy after the blood culture reports were available. Multivariable and propensity score-adjusted analysis were used to identify the risk factors associated with treatment failure. RESULTS: Among the enrolled 87 patients, 63 and 24 patients were treated with and without anaerobic coverage, respectively. Escherichia coli (55.2%) and Klebsiella pneumoniae (23.0%) were the most common organisms isolated from the blood cultures. The rate of treatment failure (relapse and 28-day mortality) was similar between the groups with and without anaerobic coverage (20.6% vs. 16.7%, p = 0.677). Propensity score-adjusted multivariable analysis revealed that definitive therapy without anaerobic coverage was not a predisposing factor for treatment failure (OR = 0.92, 95% CI 0.18-4.67, p = 0.916). CONCLUSIONS: Definitive therapy without anaerobic coverage does not affect the outcomes of patients with community-onset bacteremic BTIs without anaerobes isolated from blood. Our results might provide a possible target for antibiotic stewardship interventions in BTIs.

Geraniin suppresses ovarian cancer growth through inhibition of NF-κB activation and downregulation of Mcl-1 expression.

This study investigated the anticancer effects of geraniin on ovarian cancer cells and the signaling pathways involved. Ovarian cancer cells were treated with different concentrations of geraniin for 48 h and examined for viability, apoptosis, mitochondrial membrane depolarization, and gene expression. Xenograft tumor studies were performed to determine the anticancer activity of geraniin in vivo. Geraniin significantly decreased cancer cell viability in a concentration-dependent fashion. Geraniin significantly triggered apoptosis, which was accompanied by loss of mitochondrial membrane potential and increased cytochrome c release and caspsase-3 activity. Mechanistically, geraniin significantly downregulated Mcl-1 and impaired NF-κB p65 binding to the mcl-1 promoter. Overexpression of Mcl-1 significantly reversed geraniin-induced apoptosis in OVCAR3 cells. In addition, geraniin retarded ovarian cancer growth and reduced expression of phospho-p65 and Mcl-1. Collectively, geraniin elicits growth suppression in ovarian cancer through inhibition of NF-κB and Mcl-1 and may provide therapeutic benefits for this malignancy.