MicroRNA networks in FLT3-ITD acute myeloid leukemia.

MiR-126 and miR-155 are key microRNAs (miRNAs) that regulate, respectively, hematopoietic cell quiescence and proliferation. Herein we showed that in acute myeloid leukemia (AML), the biogenesis of these two miRNAs is interconnected through a network of regulatory loops driven by the FMS-like tyrosine kinase 3-internal tandem duplication (FLT3-ITD). In fact, FLT3-ITD induces the expression of miR-155 through a noncanonical mechanism of miRNA biogenesis that implicates cytoplasmic Drosha ribonuclease III (DROSHA). In turn, miR-155 down-regulates SH2-containing inositol phosphatase 1 (SHIP1), thereby increasing phosphor-protein kinase B (AKT) that in turn serine-phosphorylates, stabilizes, and activates Sprouty related EVH1 domain containing 1 (SPRED1). Activated SPRED1 inhibits the RAN/XPO5 complex and blocks the nucleus-to-cytoplasm transport of pre-miR-126, which cannot then complete the last steps of biogenesis. The net result is aberrantly low levels of mature miR-126 that allow quiescent leukemia blasts to be recruited into the cell cycle and proliferate. Thus, miR-126 down-regulation in proliferating AML blasts is downstream of FLT3-ITD­dependent miR-155 expression that initiates a complex circuit of concatenated regulatory feedback (i.e., miR-126/SPRED1, miR-155/human dead-box protein 3 [DDX3X]) and feed-forward (i.e., miR-155/SHIP1/AKT/miR-126) regulatory loops that eventually converge into an output signal for leukemic growth.

Chronic kidney disease may evoke anxiety by altering CRH expression in the amygdala and tryptophan metabolism in rats.

Chronic kidney disease (CKD) is associated with anxiety; however, its exact mechanism is not well understood. Therefore, the aim of the present study was to assess the effect of moderate CKD on anxiety in rats. 5/6 nephrectomy was performed in male Wistar rats. 7 weeks after, anxiety-like behavior was assessed by elevated plus maze (EPM), open field (OF), and marble burying (MB) tests. At weeks 8 and 9, urinalysis was performed, and blood and amygdala samples were collected, respectively. In the amygdala, the gene expression of Avp and the gene and protein expression of Crh, Crhr1, and Crhr2 were analyzed. Furthermore, the plasma concentration of corticosterone, uremic toxins, and tryptophan metabolites was measured by UHPLC-MS/MS. Laboratory tests confirmed the development of CKD. In the CKD group, the closed arm time increased; the central time and the total number of entries decreased in the EPM. There was a reduction in rearing, central distance and time in the OF, and fewer interactions with marbles were detected during MB. CKD evoked an upregulation of gene expression of Crh, Crhr1, and Crhr2, but not Avp, in the amygdala. However, there was no alteration in protein expression. In the CKD group, plasma concentrations of p-cresyl-sulfate, indoxyl-sulfate, kynurenine, kynurenic acid, 3-hydroxykynurenine, anthranilic acid, xanthurenic acid, 5-hydroxyindoleacetic acid, picolinic acid, and quinolinic acid increased. However, the levels of tryptophan, tryptamine, 5-hydroxytryptophan, serotonin, and tyrosine decreased. In conclusion, moderate CKD evoked anxiety-like behavior that might be mediated by the accumulation of uremic toxins and metabolites of the kynurenine pathway, but the contribution of the amygdalar CRH system to the development of anxiety seems to be negligible at this stage.

Incommensurate Antiferromagnetic Order in Weakly Frustrated Two-Dimensional van der Waals Insulator CrPSe3.

Although magnetic order is suppressed by a strong frustration, it appears in complex forms such as a cycloid or spin density wave in weakly frustrated systems. Herein, we report a weakly magnetically frustrated two-dimensional (2D) van der Waals material CrPSe3. Polycrystalline CrPSe3 was synthesized at an optimized temperature of 700 °C to avoid the formation of any secondary phases (e.g., Cr2Se3). The antiferromagnetic transition appeared at TN ≈ 127 K with a large Curie-Weiss temperature θCW ≈ -301 K via magnetic susceptibility measurements, indicating weak frustration in CrPSe3 with a frustration factor of f (|θCW|/TN) ≈ 2.4. Evidently, the formation of a long-range incommensurate antiferromagnetic order was revealed by neutron diffraction measurements at low temperatures (below 120 K). The monoclinic crystal structure of the C2/m symmetry is preserved over the studied temperature range down to 20 K, as confirmed by Raman spectroscopy measurements. Our findings on the incommensurate antiferromagnetic order in 2D magnetic materials, not previously observed in the MPX3 family, are expected to enrich the physics of magnetism at the 2D limit, thereby opening opportunities for their practical applications in spintronics and quantum devices.

Optimizing Meropenem in Highly Resistant Klebsiella pneumoniae Environments: Population Pharmacokinetics and Dosing Simulations in Critically Ill Patients.

Critically ill patients are characterized by substantial pathophysiological changes that alter the pharmacokinetics (PK) of hydrophilic antibiotics, including carbapenems. Meropenem is a key antibiotic for multidrug-resistant Gram-negative bacilli, and such pathophysiological alterations can worsen treatment outcomes. This study aimed to determine the population PK of meropenem and to propose optimized dosing regimens for the treatment of multidrug-resistant Klebsiella pneumoniae in critically ill patients. Two plasma samples were collected from eligible patients over a dosing interval. Nonparametric population PK modeling was performed using Pmetrics. Monte Carlo simulations were applied to different dosing regimens to determine the probability of target attainment and the cumulative fraction of response, taking into account the local MIC distribution for K. pneumoniae. The targets of 40% and 100% for the fraction of time that free drug concentrations remained above the MIC (ƒT>MIC) were tested, as suggested for critically ill patients. A one-compartment PK model using data from 27 patients showed high interindividual variability. Significant PK covariates were the 8-h creatinine clearance for meropenem and the presence of an indwelling catheter for pleural, abdominal, or cerebrospinal fluid drainage for the meropenem volume of distribution. The target 100% ƒT>MIC for K. pneumoniae, with a MIC of ≤2 mg/liter, could be attained by the use of a continuous infusion of 2.0 g/day. Meropenem therapy in critically ill patients could be optimized for K. pneumoniae isolates with an MIC of ≤2 mg/liter by using a continuous infusion in settings with more than 50% isolates have a MIC of ≥32mg/L.

Predicting mortality in intensive care unit patients infected with Klebsiella pneumoniae: A retrospective cohort study.

INTRODUCTION: Although several models to predict intensive care unit (ICU) mortality are available, their performance decreases in certain subpopulations because specific factors are not included. Moreover, these models often involve complex techniques and are not applicable in low-resource settings. We developed a prediction model and simplified risk score to predict 14-day mortality in ICU patients infected with Klebsiella pneumoniae. METHODOLOGY: A retrospective cohort study was conducted using data of ICU patients infected with Klebsiella pneumoniae at the largest tertiary hospital in Northern Vietnam during 2016-2018. Logistic regression was used to develop our prediction model. Model performance was assessed by calibration (area under the receiver operating characteristic curve-AUC) and discrimination (Hosmer-Lemeshow goodness-of-fit test). A simplified risk score was also constructed. RESULTS: Two hundred forty-nine patients were included, with an overall 14-day mortality of 28.9%. The final prediction model comprised six predictors: age, referral route, SOFA score, central venous catheter, intracerebral haemorrhage surgery and absence of adjunctive therapy. The model showed high predictive accuracy (AUC = 0.83; p-value Hosmer-Lemeshow test = 0.92). The risk score has a range of 0-12 corresponding to mortality risk 0-100%, which produced similar predictive performance as the original model. CONCLUSIONS: The developed prediction model and risk score provide an objective quantitative estimation of individual 14-day mortality in ICU patients infected with Klebsiella pneumoniae. The tool is highly applicable in practice to help facilitate patient stratification and management, evaluation of further interventions and allocation of resources and care, especially in low-resource settings where electronic systems to support complex models are missing.

Investigation of the Antiremodeling Effects of Losartan, Mirabegron and Their Combination on the Development of Doxorubicin-Induced Chronic Cardiotoxicity in a Rat Model.

Despite the effectiveness of doxorubicin (DOXO) as a chemotherapeutic agent, dose-dependent development of chronic cardiotoxicity limits its application. The angiotensin-II receptor blocker losartan is commonly used to treat cardiac remodeling of various etiologies. The beta-3 adrenergic receptor agonist mirabegron was reported to improve chronic heart failure. Here we investigated the effects of losartan, mirabegron and their combination on the development of DOXO-induced chronic cardiotoxicity. Male Wistar rats were divided into five groups: (i) control; (ii) DOXO-only; (iii) losartan-treated DOXO; (iv) mirabegron-treated DOXO; (v) losartan plus mirabegron-treated DOXO groups. The treatments started 5 weeks after DOXO administration. At week 8, echocardiography was performed. At week 9, left ventricles were prepared for histology, qRT-PCR, and Western blot measurements. Losartan improved diastolic but not systolic dysfunction and ameliorated SERCA2a repression in our DOXO-induced cardiotoxicity model. The DOXO-induced overexpression of Il1 and Il6 was markedly decreased by losartan and mirabegron. Mirabegron and the combination treatment improved systolic and diastolic dysfunction and significantly decreased overexpression of Smad2 and Smad3 in our DOXO-induced cardiotoxicity model. Only mirabegron reduced DOXO-induced cardiac fibrosis significantly. Mirabegron and its combination with losartan seem to be promising therapeutic tools against DOXO-induced chronic cardiotoxicity.

Arsenic Trioxide and Venetoclax Synergize against AML Progenitors by ROS Induction and Inhibition of Nrf2 Activation.

Venetoclax (VEN) in combination with hypomethylating agents induces disease remission in patients with de novo AML, however, most patients eventually relapse. AML relapse is attributed to the persistence of drug-resistant leukemia stem cells (LSCs). LSCs need to maintain low intracellular levels of reactive oxygen species (ROS). Arsenic trioxide (ATO) induces apoptosis via upregulation of ROS-induced stress to DNA-repair mechanisms. Elevated ROS levels can trigger the Nrf2 antioxidant pathway to counteract the effects of high ROS levels. We hypothesized that ATO and VEN synergize in targeting LSCs through ROS induction by ATO and the known inhibitory effect of VEN on the Nrf2 antioxidant pathway. Using cell fractionation, immunoprecipitation, RNA-knockdown, and fluorescence assays we found that ATO activated nuclear translocation of Nrf2 and increased transcription of antioxidant enzymes, thereby attenuating the induction of ROS by ATO. VEN disrupted ATO-induced Nrf2 translocation and augmented ATO-induced ROS, thus enhancing apoptosis in LSCs. Using metabolic assays and electron microscopy, we found that the ATO+VEN combination decreased mitochondrial membrane potential, mitochondria size, fatty acid oxidation and oxidative phosphorylation, all of which enhanced apoptosis of LSCs derived from both VEN-sensitive and VEN-resistant AML primary cells. Our results indicate that ATO and VEN cooperate in inducing apoptosis of LSCs through potentiation of ROS induction, suggesting ATO+VEN is a promising regimen for treatment of VEN-sensitive and -resistant AML.

Risk comparison of beta-lactam-induced anaphylaxis: Therapeutic stratification analysis in a Vietnamese pharmacovigilance database.

WHAT IS KNOWN AND OBJECTIVE: There is limited data on the specific risks of anaphylaxis induced by beta-lactam drugs. The aim of this study was to compare the risks of reporting beta-lactam-induced anaphylaxis using the national pharmacovigilance database of Vietnam (NPDV). METHODS: The multivariate generalised linear regression model was applied for signal generation and comparison of beta-lactams. RESULTS: Between 2010 and 2016, there were 2,921 reports of anaphylaxis (19.93%) from 14,655 spontaneous reports of beta-lactam use in the NDPV. Anaphylaxis signal generation was also found for the subgroup J01D (cephalosporins and carbapenems) (ROR = 1.27 [1.16-1.39]) and beta-lactamase-sensitive penicillins (ROR = 1.74 [1.27-2.35]). In the third generation cephalosporin subgroup, different risks were identified for the following combinations of beta-lactams: 1) cefotaxime with cefoperazone+sulbactam; 2) cefixime/cefpodoxime/cefdinir with cefoperazone+sulbactam or ceftizoxime/cefoperazone/ceftazidime/ceftriaxone/cefotaxime. For the second generation cephalosporin subgroup, different risks were found for cefotiam compared to cefmetazole, cefaclor, cefamandole and cefuroxime. WHAT IS NEW AND CONCLUSION: These findings identified and highlighted the different anaphylactic risks caused by various beta-lactams in the main subgroups.

Requirement of GTP binding for TIF-90-regulated ribosomal RNA synthesis and oncogenic activities in human colon cancer cells.

Transcription initiation factor 90 (TIF-90), an alternatively spliced variant of TIF-IA, differs by a 90 base pair deletion of exon 6. TIF-90 has been shown to regulate ribosomal RNA (rRNA) synthesis by interacting with polymerase I (Pol I) during the initiation of ribosomal DNA (rDNA) transcription in the nucleolus. Recently, we showed that TIF-90-mediated rRNA synthesis can play an important role in driving tumorigenesis in human colon cancer cells. Here we show that TIF-90 binds GTP at threonine 310, and that GTP binding is required for TIF-90-enhanced rRNA synthesis. Overexpression of activated AKT induces TIF-90 T310, but not a GTP-binding site (TIF-90 T310N) mutant, to translocate into the nucleolus and increase rRNA synthesis. Complementing this result, treatment with mycophenolic acid (MPA), an inhibitor of GTP production, dissociates TIF-90 from Pol I and hence abolishes AKT-increased rRNA synthesis by way of TIF-90 activation. Thus, TIF-90 requires bound GTP to fulfill its function as an enhancer of rRNA synthesis. Both TIF variants are highly expressed in colon cancer cells, and depletion of TIF-IA expression in these cells results in significant sensitivity to MPA-inhibited rRNA synthesis and reduced cell proliferation. Finally, a combination of MPA and AZD8055 (an inhibitor of both AKT and mTOR) synergistically inhibits rRNA synthesis, in vivo tumor growth, and other oncogenic activities of primary human colon cancer cells, suggesting a potential avenue for the development of therapeutic treatments by targeting the regulation of rRNA synthesis by TIF proteins.

Delamanid Resistance: Update and Clinical Management.

Delamanid, a-first-in-class bicyclic nitroimidazole, was recently approved for multidrug-resistant tuberculosis treatment. Pitted against the hope for improving treatment outcomes is the threat of the rapid resistance emergence. This review provides information on the mechanisms of action, resistance emergence, and drug susceptibility testing (DST) for delamanid. Delamanid resistance has already been reported in both in vitro experiments and clinical settings. Although mutations conferring delamanid resistance have been identified in fbiA, fbiB, fbiC, ddn, and fgd1 genes of Mycobacterium tuberculosis, knowledge about the molecular resistance mechanisms is limited, and there remains no standardized DST method. The rapid acquisition of delamanid resistance emphasizes the need for optimal use of new drugs, the need for drug resistance surveillance, and a comprehensive understanding of drug resistance mechanisms. Further studies are necessary to investigate genetic and phenotypic changes that determine clinically relevant delamanid resistance to help develop a rapid delamanid DST.

Ebp1 p48 promotes oncogenic activities in human colon cancer cells through regulation of TIF-90-mediated ribosomal RNA synthesis.

The ErbB3-binding protein 1 (Ebp1) has been reported as either an oncogenic regulator or a tumor suppressor in a variety of cancers. Here, we show that Ebp1 p48, a predominant expression isoform, is highly expressed in the majority of human colon tumor cells compared with normal adjacent tissues and its expression is required for the oncogenic activities of these cells. Depletion of Ebp1 expression in primary colon cancer cells inhibits cell proliferation, colony forming, and invasion in vitro as well as tumor formation in vivo and enhances cell sensitivity to irradiation. We further demonstrated that Ebp1 interacts with TIF-90, a splice variant of transcription initiation factor IA (TIF-IA) of the RNA polymerase I complex, allowing for regulation of ribosomal RNA (rRNA) synthesis and oncogenesis in human colon cancer cells. Moreover, Ebp1 expression is essential for Akt protected TIF-90 stability by preventing TIF-90's ubiquitination by Mdm2 and hence, its proteasomal degradation. The results of the present study support a mechanism of underlying oncogenic activities by means of Ebp1 through regulation of TIF-90-mediated rRNA synthesis and suggest the potential therapeutic treatment of colon cancer by targeting Ebp1 and its signaling.

The Bcl-2 inhibitor venetoclax inhibits Nrf2 antioxidant pathway activation induced by hypomethylating agents in AML.

Induction of reactive oxygen species (ROS), an important process for the cytotoxicity of various acute myeloid leukemia (AML) therapies including hypomethylating agents (HMAs), concurrently activates the NF-E2-related factor 2 (Nrf2) antioxidant response pathway which in turn results in induction of antioxidant enzymes that neutralize ROS. In this study, we demonstrated that Nrf2 inhibition is an additional mechanism responsible for the marked antileukemic activity in AML seen with the combination of HMAs and venetoclax (ABT-199). HMA and venetoclax combined treatment augmented mitochondrial ROS induction and apoptosis compared with treatment HMA alone. Treatment of AML cell lines as well as primary AML cells with venetoclax disrupted HMA decitabine-increased nuclear translocation of Nrf2 and induction of downstream antioxidant enzymes including heme oxygenase-1 and NADP-quinone oxidoreductase-1. Venetoclax treatment also leads to dissociation of B-cell lymphoma 2 from the Nrf2/Keap-1 complex and targets Nrf2 to ubiquitination and proteasomal degradation. Thus, our results here demonstrated an undiscovered mechanism underlying synergistic effect of decitabine and venetoclax in AML cells, elucidating for impressive results in antileukemic activity against AML in preclinical and early clinical studies by combined treatment of these drugs.

8-chloro-adenosine activity in FLT3-ITD acute myeloid leukemia.

Nucleoside analogs represent the backbone of several distinct chemotherapy regimens for acute myeloid leukemia (AML) and combination with tyrosine kinase inhibitors has improved survival of AML patients, including those harboring the poor-risk FLT3-ITD mutation. Although these compounds are effective in killing proliferating blasts, they lack activity against quiescent leukemia stem cells (LSCs), which contributes to initial treatment refractoriness or subsequent disease relapse. The reagent 8-chloro-adenosine (8-Cl-Ado) is a ribose-containing, RNA-directed nucleoside analog that is incorporated into newly transcribed RNA rather than in DNA, causing inhibition of RNA transcription. In this report, we demonstrate antileukemic activities of 8-Cl-Ado in vitro and in vivo and provide mechanistic insight into the mode of action of 8-Cl-Ado in AML. 8-Cl-Ado markedly induced apoptosis in LSC, with negligible effects on normal stem cells. 8-Cl-Ado was particularly effective against AML cell lines and primary AML blast cells harboring the FLT3-ITD mutation. FLT3-ITD is associated with high expression of miR-155. Furthermore, we demonstrate that 8-Cl-Ado inhibits miR-155 expression levels accompanied by induction of DNA-damage and suppression of cell proliferation, through regulation of miR-155/ErbB3 binding protein 1(Ebp1)/p53/PCNA signaling. Finally, we determined that combined treatment of NSG mice engrafted with FLT3-ITD + MV4-11 AML cells with 8-Cl-Ado and the FLT3 inhibitor AC220 (quizartinib) synergistically enhanced survival, compared with that of mice treated with the individual drugs, suggesting a potentially effective approach for FLT3-ITD AML patients.

Effectiveness of Community Intervention Program on Knowledge and Practice of HPV Prevention Among Married Females in Vietnam Rural Areas.

Human papillomavirus (HPV) is identified as the leading cause of cervical cancer which is the second most common cancer of females in the world. This study aimed to evaluate the effects of a community-based intervention on knowledge and practice of HPV prevention among married females aged 15 to 49 in rural areas, Vietnam. This study used a quasi-experimental design with serial cross-sectional surveys at one intervention commune (Chi Linh, Hai Duong) and one control commune at other province (Thanh Thuy, Phu Tho). Number of participants in these surveys were respectively 317 and 320 in Chi Linh and 334 and 335 in Thanh Thuy at pre- and postintervention period. The time of intervention was 15 months from April 2015 to June 2016. The study used behavior models to build up a logical framework for identifying related factors of knowledge and practice among females and developing intervention strategies. A difference-in-differences analysis approach was used to evaluate the effects of this intervention program. The study identified that the intervention had a significant change of knowledge of HPV prevention among married females after the intervention (odds ratio = 3.16, 95% confidence interval: 1.3-7.66) after adjusting for other confounders but no any significant change of practice of HPV prevention (eg, condom use, numbers of sexual partner, HPV vaccination, and screening test for cervical cancer). This might be caused by a short intervention program that did not lead to changes of practice but only change of knowledge.

Drug-induced Stevens-Johnson syndrome and toxic epidermal necrolysis in vietnamese spontaneous adverse drug reaction database: A subgroup approach to disproportionality analysis.

WHAT IS KNOWN AND OBJECTIVE: Despite the numerous studies investigating drug-induced Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN), the understanding and quantitative data in developing countries remain limited. The study aimed to describe and quantify the drug-related risk of SJS/TEN in a resource-limited context using the Vietnamese spontaneous reporting database (VSRD) of adverse drug reactions. METHODS: Spontaneous reports relating to medium- and late-onset severe cutaneous adverse reactions (MLOSCAR) and SJS/TEN recorded in the VSRD from 2010 to 2015 were retrospectively analysed. The demographic characteristics and drug information were described and compared between SJS/TEN and other MLOSCAR reports. The drug-induced SJS/TEN signals were estimated using subgrouped disproportionality analysis with calculation of the reporting odds ratio (ROR) and the respective 95% confidence interval (CI). RESULTS: The VSRD received 2,849 MLOSCAR reports, 136 of which focus on SJS/TEN over a 6-year period. About 60% of SJS/TEN patients were male, and the majority of them were adults (mean age 42.5 ± 22.9). Up to 91.8% of drugs induced SJS/TEN within 1-28 days, and 45% SJS/TEN cases were evaluated as life-threatening. Positive signals were generated with carbamazepine (n = 25, ROR [95% CI] = 11.99 [7.07-19.92]), allopurinol (n = 15, ROR [95% CI] = 4.2 [2.20-7.59]), traditional/herbal medicines (n = 7, ROR [95% CI] = 2.76 [1.12-5.86]), colchicine (n = 4, ROR [95% CI] = 6.22 [1.69-18.72]), valproic acid (n = 3, ROR [95% CI] = 8.71 [1.89-30.19]) and meloxicam (n = 3, ROR [95% CI] = 7.09 [1.55-24.29]), which are well known for SJS/TEN. Cefixime (n = 5, ROR [95% CI] = 3.34 [1.13-8.00]) and paracetamol (n = 22, ROR [95% CI] = 5.23 [3.10-8.49]) also generated positive signals despite their popularity in Vietnam. WHAT IS NEW AND CONCLUSION: This first Vietnamese population-based study has highlighted original characteristics and signals of drug-induced SJS/TEN, which are relatively consistent with other worldwide data and typical for a developing country.

The role of ErbB3 binding protein 1 in cancer: Friend or foe?

ErbB3, a member of the epidermal growth factor receptor family, reportedly plays an essential role in the regulation of cancer progression and therapeutic resistance. Numerous studies have indicated that ErbB3 binding protein 1 (Ebp1), a binding partner for ErbB3, plays an important regulatory role in the expression and function of ErbB3, but there is no agreement as to whether Ebp1 also has an ErbB3-independent function in cancer and how it might contribute to tumorigenesis. In this review, we will discuss the different functions of the two Ebp1 isoforms, p48 and p42, that may be responsible for the potentially dual role of Ebp1 in cancer growth.

Bedaquiline Resistance: Its Emergence, Mechanism, and Prevention.

Bedaquiline, a new antituberculosis drug, has already been used in >50 countries. The emergence of bedaquiline resistance is alarming, as it may result in the rapid loss of this new drug. This article aims to review currently identified mechanisms of resistance and the emergence of bedaquiline resistance, and discuss strategies to delay the resistance acquisition. In vitro and clinical studies as well as reports from compassionate use have identified the threat of bedaquiline resistance and cross-resistance with clofazimine, emphasizing the crucial need for the systematic surveillance of resistance. Currently known mechanisms of resistance include mutations within the atpE, Rv0678, and pepQ genes. The development of standardized drug susceptibility testing (DST) for bedaquiline is urgently needed. Understanding any target and non-target-based mechanisms is essential to minimize resistance development and treatment failure and help to develop appropriate DST for bedaquiline and genetic-based resistance screening.

Enhanced Light-Matter Interactions in Self-Assembled Plasmonic Nanoparticles on 2D Semiconductors.

Two-dimensional (2D) transition-metal dichalcogenide (TMD) monolayers of versatile material library are spotlighted for numerous unexplored research fields. While monolayer TMDs exhibit an efficient excitonic emission, the weak light absorption arising from their low dimensionality limits potential applications. To enhance the light-matter interactions of TMDs, while various plasmonic hybridization methods have been intensively studied, controlling plasmonic nanostructures via self-assembly processes remains challenging. Herein, strong light-matter interactions are reported in plasmonic Ag nanoparticles (NPs) hybridized on TMDs via an aging-based self-assembly process at room temperature. This hybridization is implemented by transferring MoS2 monolayers grown via chemical vapor deposition onto thin-spacer-covered Ag films. After a few weeks of aging in a vacuum desiccator, the Ag atoms in the heterolayered film diffuse to the MoS2 layers through a SiO2 spacer and self-cluster onto MoS2 point defects, resulting in the formation of Ag-NPs with an estimated diameter of ≈50 nm. The photoluminescence intensities for the Ag-NP/MoS2 hybrids are enhanced up to 35-fold compared with bare MoS2 owing to the local field enhancement near the plasmonic Ag-NPs. The localized surface plasmon resonances modes of this hybrid are systematically investigated via numerical simulations and dark-field scattering microscopy.

Antibiotic therapy for inpatients with community-acquired pneumonia in a developing country.

PURPOSE: The aim of this study was to identify antibiotic prescription patterns for community-acquired pneumonia (CAP) in Vietnam. METHODS: Medical records for CAP adult patients admitted to 10 hospitals across the country were randomly selected from admission lists during the peak pneumonia season. CAP cases were identified from manual record reviews by clinical pharmacists. Data was collected using a standard data collection tool including patient clinical features on admission, comorbidities, microbiological culture results, and antibiotic regimens. Pneumonia severity was estimated using the CURB-65 score. RESULTS: A total of 649 medical records for adult patients (55.2% male and 52.3% urban residents, median age 68 years) met the selection criteria for CAP. Pneumonia severity was assessed as mild (64.1% of patients), moderate (23.0%), and severe (9.2%). Antibiotics were most frequently administered intravenously (93.4%) and as combination therapy (dual therapy 54.4%, monotherapy 42.5%, and triple therapy 3.1% of patients) regardless of CAP severity. Third-generation cephalosporins were used most frequently (29.3% as monotherapy and 40.4% as combination therapy). Third-generation cephalosporins were most commonly combined with penicillins and/or quinolones. CONCLUSIONS: This first nationwide study provides a baseline profile of antibiotic use in the treatment of CAP. Third-generation cephalosporins were widely used for initial empirical management of CAP, often in combination with quinolones, regardless of CAP severity. The study will assist in providing an evidence base to inform new national antibiotic guidelines for CAP management and will contribute locally relevant data for the national master plan addressing antibiotic resistance and the development of educational interventions to improve CAP management.

Antibiotic Resistance, Biofilm Formation, and Persistent Phenotype of Klebsiella pneumoniae in a Vietnamese Tertiary Hospital: A Focus on Amikacin.

Klebsiella pneumoniae stands out as a major opportunistic pathogen responsible for both hospital- and community-acquired bacterial infections. This study comprehensively assesses the antibiotic resistance, amikacin persistent patterns, and biofilm-forming ability of 247 isolates of K. pneumoniae obtained from an intensive care unit of a tertiary hospital in Vietnam. Microdilution assays, conducted on a 96-well plate, determined the minimum inhibitory concentrations (MICs) of amikacin. Susceptibility data for other antibiotics were gathered from the antibiogram profile. Stationary-phase bacteria were exposed to 50 × MIC, and viable bacteria counts were measured to determine amikacin persistence. Biofilm forming capacity on 96-well polystyrene surfaces was assessed by biomass and viable bacteria. The prevalence of resistance was notably high across most antibiotics, with 64.8% classified as carbapenem-resistant K. pneumoniae and 81.4% as multidrug resistant. Amikacin, however, exhibited a relatively low rate of resistance. Of the isolates, 58.2% demonstrated a moderate to strong biofilm formation capacity, and these were found to be poorly responsive to amikacin. K. pneumoniae reveals a significant inclination for amikacin persistence, with ∼45% of isolates displaying an antibiotic antibiotic-survival ratio exceeding 10%. The study sheds light on challenges in treating of K. pneumoniae infection in Vietnam, encompassing a high prevalence of antibiotic resistance, a substantial ability to form biofilm, and a notable rate of antibiotic persistence.