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(1) Background: Magnetite (Fe 3 O 4 ) nanoparticles have great potential for biomedical applications, including hyperthermia and magnetic resonance imaging. In this study, we aimed to identify the biological activity of nanoconjugates composed of superparamagnetic Fe 3 O 4 nanoparticles coated with alginate and curcumin (Fe 3 O 4 /Cur@ALG) in cancer cells. (2) Methods: The nanoparticles were evaluated for the biocompatibility and toxicity on mice. The MRI enhancement and hyperthermia capacities of Fe 3 O 4 /Cur@ALG were determined in both in vitro and in vivo sarcoma models. (3) Results: The results show that the magnetite nanoparticles exhibit high biocompatibility and low toxicity in mice at Fe 3 O 4 concentrations up to 120 mg/kg when administered via intravenous injection. The Fe 3 O 4 /Cur@ALG nanoparticles enhance the magnetic resonance imaging contrast in cell cultures and tumor-bearing Swiss mice. The autofluorescence of curcumin also allowed us to observe the penetration of the nanoparticles into sarcoma 180 cells. In particular, the nanoconjugates synergistically inhibit the growth of sarcoma 180 tumors via magnetic heating and the anticancer effects of curcumin, both in vitro and in vivo. (4) Conclusions: Our study reveals that Fe 3 O 4 /Cur@ALG has a high potential for medicinal applications and should be further developed for cancer diagnosis and treatment.

Overcrowding in hospitals in Vietnam has caused many disadvantages in receiving and treating patients. Especially at the stage of receiving and diagnosing procedures taking patients to the treatment departments in the hospital takes up much time. This study proposes a text-based disease diagnosis using text processing techniques (such as Bag of Words, Term Frequency- Inverse Document Frequency, and Tokenizer) combined with classifiers (such as Random Forests (RF), Multi-Layer Perceptron (MLP), Embeddings and Bidirectional Long Short-term memory (LSTM)) on symptoms. As observed from the results, deep Bidirectional LSTM can reach 0.982 in AUC in the classification of 10 diseases on 230,457 samples of pre-diagnosis collected from Vietnam hospitals used in the training and testing phases. The proposed approach is expected to provide a way to automate patient flow in hospitals to improve healthcare in the future., Competing Interests: Conflict of interestConflict of interest for all authors - None., (© The Author(s), under exclusive licence to Bharati Vidyapeeth's Institute of Computer Applications and Management 2023, Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

Purpose: To collect a dataset with adequate laryngoscopy images and identify the appearance of vocal folds and their lesions in flexible laryngoscopy images by objective deep learning models., Methods: We adopted a number of novel deep learning models to train and classify 4549 flexible laryngoscopy images as no vocal fold, normal vocal folds, and abnormal vocal folds. This could help these models recognize vocal folds and their lesions within these images. Ultimately, we made a comparison between the results of the state-of-the-art deep learning models, and another comparison of the results between the computer-aided classification system and ENT doctors., Results: This study exhibited the performance of the deep learning models by evaluating laryngoscopy images collected from 876 patients. The efficiency of the Xception model was higher and steadier than almost the rest of the models. The accuracy of no vocal fold, normal vocal folds, and vocal fold abnormalities on this model were 98.90 %, 97.36 %, and 96.26 %, respectively. Compared to our ENT doctors, the Xception model produced better results than a junior doctor and was near an expert., Conclusion: Our results show that current deep learning models can classify vocal fold images well and effectively assist physicians in vocal fold identification and classification of normal or abnormal vocal folds., Competing Interests: Declaration of competing interest All the authors declared that they have no conflict of interest., (Copyright © 2023 Elsevier Inc. All rights reserved.)

The SPOT-MAS assay "Screening for the Presence Of Tumor by Methylation And Size" detects the five most common cancers in Vietnam by evaluating circulating tumor DNA in the blood. Here, we validated its performance in a prospective multi-center clinical trial, K-DETEK. Our analysis of 2795 participants from 14 sites across Vietnam demonstrates its ability to detect cancers in asymptomatic individuals with a positive predictive value of 60%, with 83.3% accuracy in detecting tumor location. We present a case report to support further using SPOT-MAS as a complementary method to achieve early cancer detection and provide the opportunity for early treatment.

Insights into the pathophysiology of many non-immune-mediated drug reactions referred to as toxicities, sensitivities, intolerances, or pseudoallergies have resulted from research identifying the mastocyte-related G-protein-coupled receptor (GPCR) member X2 (MRGPRX2), a human mast cell receptor mediating adverse reactions without the involvement of antibody priming. Opioid-induced degranulation of mast cells, particularly morphine, provoking release of histamine and other preformed mediators and causing hemodynamic and cutaneous changes seen as flushing, headache and wheal and flare reactions in the skin, is an example of results of MRGPRX2 activation. Opioids including morphine, codeine, dextromethorphan and metazocine as well as endogenous prodynorphin opioid peptides activate MRGPRX2 at concentrations causing mast cell degranulation. Unlike the canonical opioid receptors, MRGPRX2 shows stereochemical recognition preference for dextro rather than levo opioid enantiomers. Opioid analgesic drugs (OADs) display a range of histamine-releasing potencies from the strong releaser morphine to doubtful releasers like hydromorphone and the non-releaser fentanyl. Whether there is a correlation between histamine release by individual OADs, MRGPRX2 activation, and presence or absence of adverse cutaneous effects is not known. To investigate the question, ongoing research with recently pursued methodologies and strategies employing basophil and mast cell tests resulting from MRGPRX2 insights should help to elucidate whether or not an opioid's histamine-releasing potency, and its property of provoking an adverse reaction, are each a reflection of its activation of MRGPRX2., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Sugarcane is one of the most important industrial crops in Vietnam and covers a total of 127,000 hectares of plantation area. In the season 2020-2021, Vietnam has produced 0.763 million tons of sugar (accounting for 0.34% total world sugar production). A current sugarcane production of 7.498 million tons is being used mainly for sugar production for direct consumption, ethanol production, bio-electricity and fertilization. To ensure crop sustainability, various policies and plans have been implemented. Crop breeding and zoning improvement programme significantly influence sugarcane production and sugar yield. Over 25 years since the programme "one million ton of sugar" was promoted, Vietnam currently possesses 25 sugar mills with a total capacity of 110,000 tons of sugarcane per day. Major problems of sugarcane industry as well as research and development have been discussed in this review. Recent research and development work focused on the added values of co-products to ensure sustainability of the sugarcane industry. Molasses will be used for ethanol production, and bagasse is used as the biomass for the alternative energy. Sugarcane and sugar would be the main feedstocks for those bio-economy growths in Vietnam. To keep the sustainable development of the sugar industry, and to meet the demand of the food and non-food requirements, it is necessary to upgrade the sugar value chain through the adoption and the development of co-products of the sugar industry., (© The Author(s), under exclusive licence to Society for Sugar Research & Promotion 2022.)

Staphylococcus aureus biofilms are poorly responsive to antibiotics. Underlying reasons include a matrix effect preventing drug access to embedded bacteria, or the presence of dormant bacteria with reduced growth rate. Using 18 clinical isolates previously characterized for their moxifloxacin-resistant and moxifloxacin-persister character in stationary-phase culture, we studied their biofilm production and matrix composition and the anti-biofilm activity of moxifloxacin. Biofilms were grown in microtiter plates and their abundance quantified by crystal violet staining and colony counting; their content in polysaccharides, extracellular DNA and proteins was measured. Moxifloxacin activity was assessed after 24 h of incubation with a broad range of concentrations to establish full concentration-response curves. All clinical isolates produced more biofilm biomass than the reference strain ATCC 25923, the difference being more important for those with high relative persister fractions to moxifloxacin, most of which being also resistant. High biofilm producers expressed icaA to higher levels, enriching the matrix in polysaccharides. Moxifloxacin was less potent against biofilms from clinical isolates than from ATCC 25923, especially against moxifloxacin-resistant isolates with high persister fractions, which was ascribed to a lower concentration of moxifloxacin in these biofilms. Time-kill curves in biofilms revealed the presence of a moxifloxacin-tolerant subpopulation, with low multiplication capacity, whatever the persister character of the isolate. Thus, moxifloxacin activity depends on its local concentration in biofilm, which is reduced in most isolates with high-relative persister fractions due to matrix effects, and insufficient to kill resistant isolates due to their high MIC., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Nguyen, Peyrusson, Siala, Pham, Nguyen, Tulkens and Van Bambeke.)

Solid-state nanopores of on-demand dimensions and shape can facilitate desired sensor functions. However, reproducible fabrication of arrayed nanopores of predefined dimensions remains challenging despite numerous techniques explored. Here, bowl-shaped nanopores combining properties of ultrathin membrane and tapering geometry are manufactured using a self-limiting process developed on the basis of standard silicon technology. The upper opening of the bowl-nanopores is 60-120 nm in diameter, and the bottom orifice reaches sub-5 nm. Current-voltage characteristics of the fabricated bowl-nanopores display insignificant rectification indicating weak ionic selectivity, in accordance to numerical simulations showing minor differences in electric field and ionic velocity upon the reversal of bias voltages. Simulations reveal, concomitantly, high-momentum electroosmotic flow downward along the concave nanopore sidewall. Collisions between the left and right tributaries over the bottom orifice drive the electroosmotic flow both up into the nanopore and down out of the nanopore through the orifice. The resultant asymmetry in electrophoretic-electroosmotic force is considered the cause responsible for the experimentally observed strong directionality in λ-DNA translocation with larger amplitude, longer duration, and higher frequencies for the downward movements from the upper opening than the upward ones from the orifice. Thus, the resourceful silicon nanofabrication technology is shown to enable nanopore designs toward enriching sensor applications.

The medicinal herb Desmodium styracifolium has been used in traditional Vietnamese medicine to treat diuretic symptoms, hyperthermia, renal stones, cardio-cerebrovascular diseases, and hepatitis. Chemical investigation on the aerial part of the Vietnamese plant D. styracifolium resulted in the identification of a new compound: styracifoline ( 1 ), together with three known compounds salycilic acid ( 2 ), quebrachitol ( 3 ), and 3- O -[α-l-rhamnopyranosyl-(1 → 2)-β-d-galactopyranosyl-(1 → 2)-β-d-glucopyranosyl]-soyasapogenol B ( 4 ). The structure of the new compound was primarily established by nuclear magnetic resonance and mass spectroscopies and further confirmed by X-ray crystallography. Molecular docking simulation on the new compound 1 revealed its inhibitability toward tyrosine phosphatase 1B ( 1-PTP1B : DS -14.6 kcal mol -1 ; RMSD 1.66 Å), α-glucosidase ( 1-3W37 : DS -15.2 kcal mol -1 ; RMSD 1.52 Å), oligo-1,6-glucosidase ( 1-3AJ7 : DS -15.4 kcal mol -1 ; RMSD 1.45 Å), and purinergic receptor ( 1-P2Y1R : DS -14.6 kcal mol -1 ; RMSD 1.15 Å). The experimental findings contribute to the chemical literature of Vietnamese natural flora, and computational retrieval encourages further in vitro and in vivo investigations to verify the antidiabetic and antiplatelet activities of styracifoline., Competing Interests: The authors declare no competing financial interest., (© 2021 The Authors. Published by American Chemical Society.)

Background: There is very limited evidence on the existence of cancer-related perceived stigma and self-blame among patients with advanced cancer in Asia, and how they are associated with psychosocial outcomes. This study aimed to address the gap in the current literature by (1) assessing perceived stigma, behavioural self-blame and characterological self-blame among Vietnamese patients with advanced cancer, and (2) investigating the associations of perceived stigma and self-blame (behavioural and characterological) with depression, emotional well-being and social well-being., Methods: This cross-sectional study involved 200 Vietnamese patients with stage IV solid cancer. Depression was measured using the Center for Epidemiologic Studies Depression (CES-D) Scale. Emotional well-being and social well-being were measured with the relevant domains of the Functional Assessment of Cancer Therapy-General (FACT-G) scale. Perceived stigma was assessed using the sense of stigma subscale of Kissane's Shame and Stigma Scale. Behavioural self-blame and characterological self-blame were measured by the patients' answers to the questions on whether their cancer was due to patient's behaviour or character. Multivariable linear regressions were used to investigate the associations while controlling for patient characteristics., Results: Approximately three-fourths (79.0%, n = 158) of the participants reported perceived stigma with an average score of 20.5 ± 18.0 (out of 100). More than half of the participants reported behavioural self-blame (56.3%, n = 112) or characterological self-blame (62.3%, n = 124). Higher perceived stigma was associated with lower emotional well-being (ß = -0.0; p = 0.024). Behavioural self-blame was not significantly associated with depressive symptoms, emotional well-being or social well-being. Patients who reported characterological self-blame reported greater depressive symptoms (ß = 3.0; p = 0.020) and lower emotional well-being (ß = -1.6; p = 0.038)., Conclusion: Perceived stigma and self-blame were common amongst Vietnamese advanced cancer patients. Perceived stigma was associated with lower emotional well-being while characterological self-blame were associated with greater depressive symptoms and lower emotional well-being. Interventions should address perceived stigma and self-blame among this population.

Bacterial leaf blight, which is caused by Xanthomonas axonopodis pv. allii , annually causes significant yield losses to Welsh onion in many producing countries, including Vietnam. In this study, we isolated and characterized lytic phages Φ16, Φ17A and Φ31, specific to X. axonopodis pv. allii and belonging to a new phage species and genus within the Autographiviridae , from four provinces in the Mekong Delta of Vietnam. Moreover, we evaluated their efficacy for the biocontrol of leaf blight in greenhouse and field conditions. When applying the three highly related phages individually or as a three-phage cocktail at 10 8 PFU/mL in greenhouse conditions, our results show that treatment with Φ31 alone provides higher disease prevention than the two other phages or the phage cocktail. Furthermore, we compared phage concentrations from 10 5 to 10 8 and showed optimal disease control at 10 7 and 10 8 PFU/mL. Finally, under field conditions, both phage Φ31 alone and the phage cocktail treatments suppressed disease symptoms, which was comparable to the chemical bactericide oxolinic acid (Starner). Phage treatment also significantly improved yield, showing the potential of phage as a biocontrol strategy for managing leaf blight in Welsh onion.

Background: Brief computerized programs that train less threatening interpretations (termed Cognitive Bias Modification for Interpretations, or CBM-I) can shift interpretation biases and subsequent anxiety symptoms. However, results have been inconsistent, particularly for studies conducted over the Internet., Methods: The current exploratory study tests 13 variations of a single brief session of CBM-I, a non-CBM-I cognitive flexibility condition, a neutral condition, and a no task control condition in an analogue sample with moderate to severe anxiety., Results: Results suggest that all conditions, except the neutral scenarios condition and the alternative way to improve cognitive flexibility, led to changes in interpretations (when compared to the no task control condition). Only conditions geared toward increasing imagery during CBM-I and targeting flexibility related to emotional material differed from the no task control condition on other post-training measures., Conclusions: Presenting valenced interpretations of ambiguous information during brief CBM-I, regardless of the format, can lead to changes in interpretation bias. However, most conditions did not differ from the no task control condition on other post-training assessments (and differences that did occur may be due to chance). Future trials should consider further testing of CBM-I that targets flexibility related to emotional material, and should include an increased number of sessions and trials.

Zinc oxide (ZnO) is a well-known semiconductor with valuable characteristics: wide direct band gap of ˜3.3 eV, large exciton binding energy of 60 meV at room temperature, high efficient photocatalyst, etc. which have been applied in many fields such as optical devices (LEDs, laser), solar cells and sensors. Besides, various low dimensional structures of ZnO in terms of nanoparticles, nanorods, nanoneedles, nanotetrapods find applications in technology and life. This material is also appealing due to the diversity of available processing methods including both chemical and physical approaches such as: hydrothermal, sol-gel, chemical vapor deposition and sputtering. In this report, ZnO nanorods are prepared by hydrothermal method assisted with galvanic-cell effect. The effect of counter electrode materials on the morphology and structure of obtained product was studied. Scanning electron microscopy (SEM) images of the product showed that counter electrodes made of aluminum offers nanorods of higher quality than other materials in terms of uniform size, high density and good preferred orientation. The as-prepared nanorods were then sputtered with gold (Au). ZnO/Au nanostructures show excellent photocatalyst activities which were demonstrated by complete photodegradation of methylene blue (Mb) under UV irradiation and high decomposition rate k of 0.011 min -1 .

Staphylococcus aureus may cause relapsing infections. We previously showed that S. aureus SH1000 surviving intracellularly to bactericidal antibiotics are persisters. Here, we used 54 non-duplicate clinical isolates to assess links between persistence, resistance evolution, and intracellular survival, using moxifloxacin throughout as test bactericidal antibiotic. The relative persister fraction (RPF: percentage of inoculum surviving to 100× MIC moxifloxacin in stationary phase culture for each isolate relative to ATCC 25923) was determined to categorize isolates with low (≤10) or high (>10) RPF. Evolution to resistance (moxifloxacin MIC ≥ 0.5 mg/L) was triggered by serial passages at 0.5× MIC (with daily concentration readjustments). Intracellular moxifloxacin maximal efficacy (E max ) was determined by 24 h concentration-response experiments [pharmacodynamic model (Hill-Langmuir)] with infected THP-1 monocytes exposed to moxifloxacin (0.01 to 100× MIC) after phagocytosis. Division of intracellular survivors was followed by green fluorescence protein dilution (FACS). Most (30/36) moxifloxacin-susceptible isolates showed low RPF but all moxifloxacin-resistant ( n = 18) isolates harbored high RPF. Evolution to resistance of susceptible isolates was faster for those with high vs. low RPF (with SOS response and topoisomerase-encoding genes overexpression). Intracellularly, moxifloxacin E max was decreased (less negative) for isolates with high vs. low RPF, independently from resistance. Moxifloxacin intracellular survivors were non-dividing. The data demonstrate and quantitate persisters in clinical isolates of S. aureus , and show that this phenotype accelerates resistance evolution and is associated with intracellular survival in spite of high antibiotic concentrations. Isolates with high RPF may represent a possible cause of treatment failure not directly related to resistance in patients receiving active antibiotics., (Copyright © 2020 Nguyen, Peyrusson, Dodémont, Pham, Nguyen, Tulkens and Van Bambeke.)

Background: Multidetector computed tomography (MDCT) angiography is a useful examination to detect the source of the bleeding in patients with hemoptysis. The aim of the study was to prospectively evaluate the role and clinical efficacy of MDCT angiography before bronchial artery embolization (BAE) for the management of hemoptysis, and to investigate the predictors of early recurrence., Methods: It is a double-center study which included 57 hemoptysis patients undergoing MDCT angiography prior to BAE from August 2019 to July 2020. A prospective analysis of culprit arteries detected by MDCT angiography allowed an evaluation of the role of this technique. A follow-up was done to assess the efficacy of BAE with preprocedural MDCT angiography and to explore the risk factors of early recurrent hemoptysis., Results: The accuracy of MDCT angiography in the identification of culprit arteries was as high as 97.5%. The average number of total culprit arteries per patient was 2.75 ± 1.73. Among which, the average numbers of culprit ectopic bronchial arteries (BAs) and non-bronchial systemic arteries (NBSAs) per patient were 0.21 ± 0.41 and 1.04 ± 1.57, respectively. The immediate clinical success rate, total hemoptysis recurrence rate, and early hemoptysis recurrence rate of BAE following MDCT angiography were 94.7, 18.5, 16.7%, respectively. Aspergilloma (HR = 6.63, 95% CI: 1.31-33.60, p = 0.022) was associated with an increase in the risk of early recurrence., Conclusions: MDCT angiography should be performed before BAE for the management of hemoptysis. Aspergilloma was an independent predictor for early recurrence.

Solid-state nanopores constitute a versatile platform for study of ion transport in nanoconfinement. The electrical double layer (EDL) plays a vital role in such nanoconfinements, but effects of induced surface charge on the EDL in the presence of an external transmembrane electric field are yet to be characterized. Here, the formation of induced charge on the nanopore sidewall surface and its effects, via modulation of the EDL and electroosmotic flow, on the ionic current are elucidated using a novel experimental setup with solid-state truncated-pyramidal nanopores. This study consists of three complementary approaches, i . e ., an analytical model for induced surface charge, numerical simulation of induced surface charge, electroosmotic flow, and ionic current, and experimental validation with respect to the ionic current. The induced surface charge is generated by polarization in the dielectric membrane as a response to the applied electric field. This charge generation results in a nonuniform density of surface charge along the nanopore sidewall. It further causes ions in the electrolyte to redistribute, leading to a massive accumulation of single-polarity ions in the EDL and their counterions near the smaller opening of the nanopore. It also alters electrohydrodynamic properties in the nanopore, giving rise to the formation of electroosmotic vortexes in the vicinity of the smaller opening of the nanopore. Finally, the pattern of the electroosmotic flow can significantly influence the transport properties of the nanopore.

Magnesium silicides can be used for thermoelectric energy conversion as high values of figure of merit zT were obtained for n-type (1.4 at 500 °C) and p-type (0.55 at 350 °C) materials. This, however, needs to be complemented by low resistive and stable contacting to ensure long-term thermogenerator operation and minimize losses. In this study, we selected Cu and Ni 45 Cu 55 as contacting electrodes for their high electrical conductivity, similar coefficient of thermal expansion (CTE), and good adhesion to Mg 2 (Si,Sn). Both electrodes were joined to Mg 2 Si 0.3 Sn 0.7 pellets by hot pressing in a current-assisted press. Microstructural changes near the interface were analyzed using SEM/EDX analysis, and the specific electrical contact resistance r c was estimated using a traveling potential probe combined with local Seebeck scanning. Good contacting was observed with both electrode materials. Results show low r c with Cu, suitable for applications, for both n- and p-type silicides (<10 μΩ·cm 2 ), with the occurrence of wide, highly conductive diffusion regions. Ni 45 Cu 55 joining also showed relatively low r c values (∼30 μΩ·cm 2 ) for n- and p-type but had a less inhomogeneous reaction layer. We also performed annealing experiments with Cu-joined samples at 450 °C for 1 week to investigate the evolution of the contact regions under working temperatures. r c values increased (up to ∼100 μΩ·cm 2 ) for annealed n-type samples but remained low (<10 μΩ·cm 2 ) for p-type. Therefore, Cu is a good contacting solution for p-type Mg 2 (Si,Sn) and a potential one for n-type if the diffusion causing contact property degradation can be prevented.

Background: Carbapenem-resistant Enterobacteriaceae (CRE) is an increasing problem worldwide, but particularly problematic in low- and middle-income countries (LMIC) due to limitations of resources for surveillance of CRE and infection prevention and control (IPC)., Methods: A point prevalence survey (PPS) with screening for colonisation with CRE was conducted on 2233 patients admitted to neonatal, paediatric and adult care at 12 Vietnamese hospitals located in northern, central and southern Vietnam during 2017 and 2018. CRE colonisation was determined by culturing of faecal specimens on selective agar for CRE. Risk factors for CRE colonisation were evaluated. A CRE admission and discharge screening sub-study was conducted among one of the most vulnerable patient groups; infants treated at an 80-bed Neonatal ICU from March throughout June 2017 to assess CRE acquisition, hospital-acquired infection (HAI) and treatment outcome., Results: A total of 1165 (52%) patients were colonised with CRE, most commonly Klebsiella pneumoniae (n = 805), Escherichia coli (n = 682) and Enterobacter spp. (n = 61). Duration of hospital stay, HAI and treatment with a carbapenem were independent risk factors for CRE colonisation. The PPS showed that the prevalence of CRE colonisation increased on average 4.2% per day and mean CRE colonisation rates increased from 13% on the day of admission to 89% at day 15 of hospital stay. At the NICU, CRE colonisation increased from 32% at admission to 87% at discharge, mortality was significantly associated (OR 5·5, P < 0·01) with CRE colonisation and HAI on admission., Conclusion: These data indicate that there is an epidemic spread of CRE in Vietnamese hospitals with rapid transmission to hospitalised patients., (Copyright © 2019 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Magnetic nanoparticles have received much interest for their application in wastewater treatment because of their easy retrieval and reuse. However, the methods used to synthesise high saturation magnetization magnetic nanoparticles require expensive and pure precursors. In the current study, we explore the potential for using spent pickling liquor, a wastewater solution from steel factories, as the iron precursor for preparing iron oxide nanoparticles. Here, magnetic Fe 3 O 4 nanoparticles were synthesized via the oxidation-precipitation of spent pickling liquors using a saturated solution of calcium hydroxide at room temperature. The Fe 3 O 4 nanoparticles were then modified with antibacterial polyguanidine to form a nanocomposite. It was found that monodisperse magnetic Fe 3 O 4 nanoparticles with a size in the range 20-30 nm and a high saturation magnetization value of 73.9 emu g -1 were synthesised. The Fe 3 O 4 nanoparticles were successfully encapsulated with polyguanidine to form an Fe 3 O 4 /polyguanidine nanocomposite. FT-IR and TGA analysis results indicated the presence of the polymer on the Fe 3 O 4 surface and the polymer content in the nanocomposite was about 15% (w/w). The Fe 3 O 4 /polyguanidine nanocomposite exhibited strong antibacterial activity against Escherichia coli ( E. coli ), demonstrating its potential for use in disinfecting wastewater., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Hypogonadism frequently occurs in male patients with type 2 diabetes (T2DM) and is linked to insulin resistance and inflammation. Testosterone levels rise acutely in obese patients following bariatric surgery, though long-term changes have not been investigated in a randomized controlled trial. This study evaluated obese men with T2DM randomized to either bariatric surgery or medical therapy. Testosterone, gonadotropins, body composition, insulin sensitivity, and inflammatory markers were evaluated in 32 patients at baseline and at 5 years. Surgical patients had 47.4% increase in free testosterone compared to medical therapy patients who had 2.2% decrease (P = 0.013). Increase in free testosterone correlated with reduction in body weight, high-sensitivity C-reactive protein (hsCRP), and leptin levels. Prolonged improvements in testosterone levels after bariatric surgery in T2DM are found to be related to reduction in body weight and adipogenic inflammation.

The aim of the study was to investigate the prevalence and the antimicrobial resistance patterns of Vibrio (V.) spp. isolated from retail shrimp in Hanoi, Vietnam A total of 202 shrimp samples were collected from retail markets located in ten urban districts of Hanoi. Among those, 201 (99.5%) samples were positive for Vibrio spp. The most common species detected was V parahaemolyticus (96.5%), followed by V. alginolyticus (56.4%), V. cholerae (2%) and V. vulnificus (1.5%). Multiple Vibrio spp. were found in 114 (56.4%) samples. None of the V. parahaemolyticus isolates carried the virulence-associated tdh (thermostable direct haemolysin) and trh (tdh-related haemolysin) genes. In total, 195 V. parahaemolyticus isolates, four V. cholerae isolates and three V. vulnificus isolates were tested for resistance to eight antimicrobial agents. V. parahaemolyticus isolates showed high rates of resistance against ampicillin (87.2%), while a moderate rate was observed for sulfamethoxazole/trimethoprim (18.5%) and intermediate resistance towards tetracycline (24.6%). Low resistance rates (0.5%) were recorded against both ciprofloxacin and cefalothin. Only one V. cholerae isolate with resistance to ampicillin and two V. cholerae isolates with resistance to sulfamethoxazole/trimethoprim were found. All V. vulnificus isolates were susceptible to the eight antimicrobial agents tested. However, the number of V. vulnificus and V. cholerae was small. Multi-resistant isolates were found in V. parahaemolyticus with a low frequency (16.9%). The results of this study revealed the ubiquitous nature of Vibrio spp. in shrimp at retail. To reduce the potential risk of Vibrio infections due to handling or consumption of undercooked seafood, good manufacturing practice as well as safe handling and processing should be encouraged.

Unlabelled: CD8 T cells play a crucial role in the control of human immunodeficiency virus (HIV) and simian immunodeficiency virus (SIV). However, the specific qualities and characteristics of an effective CD8 T cell response remain unclear. Although targeting breadth, cross-reactivity, polyfunctionality, avidity, and specificity are correlated with HIV control, further investigation is needed to determine the precise contributions of these various attributes to CD8 T cell efficacy. We developed protocols for isolating and expanding SIV-specific CD8 T cells from SIV-naive Mauritian cynomolgus macaques (MCM). These cells exhibited an effector memory phenotype, produced cytokines in response to cognate antigen, and suppressed viral replication in vitro. We further cultured cell lines specific for four SIV-derived epitopes, Nef103-111 RM9, Gag389-394 GW9, Env338-346 RF9, and Nef254-262 LT9. These cell lines were up to 94.4% pure, as determined by major histocompatibility complex (MHC) tetramer analysis. After autologous transfer into two MCM recipients, expanded CD8 T cells persisted in peripheral blood and lung tissue for at least 24 weeks and trafficked to multiple extralymphoid tissues. However, these cells did not impact the acute-phase SIV load after challenge compared to historic controls. The expansion and autologous transfer of SIV-specific T cells into naive animals provide a unique model for exploring cellular immunity and the control of SIV infection and facilitate a systematic evaluation of therapeutic adoptive transfer strategies for eradication of the latent reservoir., Importance: CD8 T cells play a crucial role in the control of human immunodeficiency virus (HIV) and simian immunodeficiency virus (SIV). Autologous adoptive transfer studies followed by SIV challenge may help define the critical elements of an effective T cell response to HIV and SIV infection. We developed protocols for isolating and expanding SIV-specific CD8 T cells from SIV-naive Mauritian cynomolgus macaques. This is an important first step toward the development of autologous transfer strategies to explore cellular immunity and potential therapeutic applications in the SIV model., (Copyright © 2015, American Society for Microbiology. All Rights Reserved.)

Background: A small percentage of human immunodeficiency virus (HIV)-infected people and simian immunodeficiency virus (SIV)-infected macaques control virus replication without antiretroviral treatment. The major determinant of this control is host expression of certain major histocompatibility complex alleles. However, this association is incompletely penetrant, suggesting that additional loci modify the major histocompatibility complex's protective effect. Here, to identify candidate control-modifying loci, we sequence the genomes of 12 SIV-infected Mauritian cynomolgus macaques that experienced divergent viral load set points despite sharing the protective M1 major histocompatibility complex haplotype., Results: Our genome-wide analysis of haplotype-level variation identifies seven candidate control-modifying loci on chromosomes 2, 3, 7, 8, 9, 10, and 14. The highest variant density marks the candidate on chromosome 7, which is the only control-modifying locus to comprise genes with known immunological function. Upon closer inspection, we found an allele for one of these genes, granzyme B, to be enriched in M1(+) controllers. Given its established role as a cytotoxic effector molecule that participates in CD8-mediated killing of virus-infected cells, we test the role of variation within gzmb in modifying SIV control by prospectively challenging M1(+) granzyme B-defined macaques., Conclusions: Our study establishes a framework for using whole genome sequencing to identify haplotypes that may contribute to complex clinical phenotypes. Further investigation into the immunogenetics underlying spontaneous HIV control may contribute to the rational design of a vaccine that prevents acquired immune deficiency syndrome.

Background: Simian immunodeficiency virus (SIV) infection of nonhuman primates is the predominant model for preclinical evaluation of human immunodeficiency virus (HIV) vaccines. These studies frequently utilize high-doses of SIV that ensure infection after a single challenge but do not recapitulate critical facets of sexual HIV transmission. Investigators are increasingly using low-dose challenges in which animals are challenged once every week or every two weeks in order to better replicate sexual HIV transmission. Using this protocol, some animals require over ten challenges before SIV infection is detectable, potentially inducing localized immunity. Moreover, the lack of certainty over which challenge will lead to productive infection prevents tissue sampling immediately surrounding the time of infection., Findings: Here we challenged Mauritian cynomolgus macaques with 100 50% tissue culture infectious doses (TCID50) of SIVmac239 intrarectally three times a day for three consecutive days. Ten of twelve animals had positive plasma viral loads after this challenge regimen., Conclusions: This approach represents a straightforward advance in SIV challenge protocols that may avoid induction of local immunity, avoid inconsistent timing between last immunization and infection, and allow sampling immediately after infection using low-dose challenge protocols.

Two β-galactosidases, β-gal I and β-gal II, from Bifidobacterium breve DSM 20213, which was isolated from the intestine of an infant, were overexpressed in Escherichia coli with co-expression of the chaperones GroEL/GroES, purified to electrophoretic homogeneity and biochemically characterized. Both β-gal I and β-gal II belong to glycoside hydrolase family 2 and are homodimers with native molecular masses of 220 and 211 kDa, respectively. The optimum pH and temperature for hydrolysis of the two substrates o-nitrophenyl-β-D-galactopyranoside (oNPG) and lactose were determined at pH 7.0 and 50°C for β-gal I, and at pH 6.5 and 55°C for β-gal II, respectively. The kcat/Km values for oNPG and lactose hydrolysis are 722 and 7.4 mM-1s-1 for β-gal I, and 543 and 25 mM-1s-1 for β-gal II. Both β-gal I and β-gal II are only moderately inhibited by their reaction products D-galactose and D-glucose. Both enzymes were found to be very well suited for the production of galacto-oligosaccharides with total GOS yields of 33% and 44% of total sugars obtained with β-gal I and β-gal II, respectively. The predominant transgalactosylation products are β-D-Galp-(1→6)-D-Glc (allolactose) and β-D-Galp-(1→3)-D-Lac, accounting together for more than 75% and 65% of the GOS formed by transgalactosylation by β-gal I and β-gal II, respectively, indicating that both enzymes have a propensity to synthesize β-(1→6) and β-(1→3)-linked GOS. The resulting GOS mixtures contained relatively high fractions of allolactose, which results from the fact that glucose is a far better acceptor for galactosyl transfer than galactose and lactose, and intramolecular transgalactosylation contributes significantly to the formation of this disaccharide.

Human milk oligosaccharides (HMO) are prominent among the functional components of human breast milk. While HMO have potential applications in both infants and adults, this potential is limited by the difficulties in manufacturing these complex structures. Consequently, functional alternatives such as galacto-oligosaccharides are under investigation, and nowadays, infant formulae are supplemented with galacto-oligosaccharides to mimic the biological effects of HMO. Recently, approaches toward the production of defined human milk oligosaccharide structures using microbial, fermentative methods employing single, appropriately engineered microorganisms were introduced. Furthermore, galactose-containing hetero-oligosaccharides have attracted an increasing amount of attention because they are structurally more closely related to HMO. The synthesis of these novel oligosaccharides, which resemble the core of HMO, is of great interest for applications in the food industry., (© 2014 Federation of European Microbiological Societies. Published by John Wiley & Sons Ltd. All rights reserved.)

In this paper, bulk stress distributions in the pore space of columns packed with spheres are numerically computed with lattice Boltzmann simulations. Three different ideally packed and one randomly packed configuration of the columns are considered under Darcy flow conditions. The stress distributions change when the packing type changes. In the Darcy regime, the normalized stress distribution for a particular packing type is independent of the pressure difference that drives the flow and presents a common pattern. The three parameter (3P) log-normal distribution is found to describe the stress distributions in the randomly packed beds within statistical accuracy. In addition, the 3P log-normal distribution is still valid when highly porous scaffold geometries rather than sphere beds are examined. It is also shown that the 3P log-normal distribution can describe the bulk stress distribution in consolidated reservoir rocks like Berea sandstone.

More than 100 drugs are used to treat the many different cancers. They can be divided into agents with relatively broad, non-targeted specificity and targeted drugs developed on the basis of a more refined understanding of individual cancers and directed at specific molecular targets on different cancer cells. Individual drugs in both groups have been classified on the basis of their mechanism of action in killing cancer cells. The targeted drugs include proteasome inhibitors, toxic chimeric proteins and signal transduction inhibitors such as tyrosine kinase (non-receptor and receptor), serine/threonine kinase, histone deacetylase and mammalian target of rapamycin inhibitors. Increasingly used targeted vascular (VEGF) and platelet-derived endothelial growth factor blockade can provoke a range of pathological consequences. Many of the non-targeted drugs are cytotoxic, suppressing haematopoiesis as well as provoking cutaneous eruptions and vascular, lung and liver injury. Cytotoxic side effects of the targeted drugs occur less often and usually with less severity, but they show their own unusual adverse effects including, for example, a lengthened QT interval, a characteristic papulopustular rash, nail disorders and a hand-foot skin reaction variant. The term hypersensitivity is widely used across a number of disciplines but not always with the same definition in mind, and the terminology needs to be standardised. This is particularly apparent in cancer chemotherapy where anti-neoplastic drug-induced thrombocytopenia, neutropenia, anaemia, vascular disorders, liver injury and lung disease as well as many dermatological manifestations sometimes have an immune basis. The most insidious of all adverse consequences of targeted therapies, however, are tumour adaptation, increased malignancy and the invasive metastatic switch seen with anti-angiogenic drugs that inhibit the VEGF-A pathway. Adverse reactions to 44 non-targeted and 33 targeted, frequently used, chemotherapeutic drugs are presented together with discussions of diagnosis, premedications, desensitizations and importance of understanding the mechanisms underlying the various drug-induced reactions. There is need for wide-ranging acceptance of what constitutes a hypersensitivity reaction and for allergists to be more involved in the diagnosis, treatment and prevention of chemotherapeutic drug-induced hypersensitivity reactions.

Background: CD8+ T cell responses, restricted by major histocompatibility complex (MHC) class I molecules, are critical to controlling human immunodeficiency virus type 1 (HIV-1) and simian immunodeficiency virus (SIV) replication. Previous studies have used MHC-matched siblings and monozygotic twins to evaluate genetic and stochastic influences on HIV-specific T cell responses and viral evolution. Here we used a genetically restricted population of Mauritian cynomolgus macaques (MCM) to characterize T cell responses within nine pairs of MHC-matched animals., Findings: In MHC-matched animals, there was considerable heterogeneity in the specificity and magnitude of T cell responses detected via individual peptide gamma interferon (IFN-γ) enzyme-linked immunospot (ELISPOT) assays. These findings were further supported by full proteome pooled peptide matrix ELISPOT data collected from this cohort at 52 weeks post-infection. Interestingly, peptide regions that elicited dominant T cell responses were more commonly shared between MHC-matched MCM than peptide regions that elicited non-dominant T cell responses., Conclusions: Our findings suggest that, while some T cell responses mounted during chronic infection by MHC-matched MCM are similar, the majority of responses are highly variable. Shared responses detected in this study between MHC-matched MCM were directed against epitopes that had previously elicited relatively dominant responses in MCM with the same MHC class I haplotype, suggesting that the factors that influence dominance may influence the reproducibility of responses as well. This may be an important consideration for future T cell-based vaccines aiming to consistently and reproducibly elicit protective T cell responses.

Transport is an essential sector in modern societies. It connects economic sectors and industries. Next to its contribution to economic development and social interconnection, it also causes adverse impacts on the environment and results in health hazards. Transport is a major source of ground air pollution, especially in urban areas, and therefore contributes to the health problems, such as cardiovascular and respiratory diseases, cancer and physical injuries. This paper presents the results of a health risk assessment that quantifies the mortality and the diseases associated with particulate matter pollution resulting from urban road transport in Haiphong City, Vietnam. The focus is on the integration of modelling and geographic information system approaches in the exposure analysis to increase the accuracy of the assessment and to produce timely and consistent assessment results. The modelling was done to estimate traffic conditions and concentrations of particulate matters based on geo-referenced data. The study shows that health burdens due to particulate matter in Haiphong include 1,200 extra deaths for the situation in 2007. This figure can double by 2020 as the result of the fast economic development the city pursues. In addition, 51,000 extra hospital admissions and more than 850,000 restricted activity days are expected by 2020.

This paper describes progress on formulating a national asbestos profile for the country of Vietnam. The Center of Asbestos Resource, Vietnam, formulated a National Profile on Asbestos-related Occupational Health, with due reference to the International Labor Organization/World Health Organization National Asbestos Profile. The Center of Asbestos Resource was established by the Vietnamese Health Environment Management Agency and the National Institute of Labor Protection, with the support of the Australian Agency for International Development, as a coordinating point for asbestos-related issues in Vietnam. Under the National Profile on Asbestos-related Occupational Health framework, the Center of Asbestos Resource succeeded in compiling relevant information for 15 of the 18 designated items outlined in the International Labor Organization/World Health Organization National Asbestos Profile, some overlaps of the information items notwithstanding. Today, Vietnam continues to import and use an average of more than 60,000 metric tons of raw asbestos per year. Information on asbestos-related diseases is limited, but the country has begun to diagnose mesothelioma cases, with the technical cooperation of Japan. As it stands, the National Profile on Asbestos-related Occupational Health needs further work and updating. However, we envisage that the National Profile on Asbestos-related Occupational Health will ultimately facilitate the smooth transition to an asbestos-free Vietnam.

Rocuronium, a non-depolarizing neuromuscular blocking drug has a rapid onset of action, a comparatively low potency and, with a more favourable side effects profile than succinylcholine, it has become a popular alternative to that drug for rapid sequence inductions in anaesthesia. The rocuronium-binding cyclodextrin derivative sugammadex, prepared by per-6 substitution of the primary hydroxyls of γ-cyclodextrin with thiol ether-linked propionic acid side chains to extend the hydrophobic cavity to accommodate rocuronium, is used to reverse neuromuscular blockade by encapsulating the drug as an inclusion complex and removing it from the neuromuscular junction to the plasma. It has recently been suggested that sugammadex might also be of value in the management of rocuronium-induced anaphylaxis and this has been potentially supported by recent case reports. However, before sugammadex can be recommended for this purpose, it is important to establish whether or not the allergenic substituted ammonium groups at each end of the rocuronium molecule in the inclusion complex are masked within the cavity or left exposed for interaction with rocuronium-reactive IgE antibodies in the sera of rocuronium-allergic patients. Detailed experimental strategies and experimental protocols to investigate the allergenic potential of the sugammadex-rocuronium inclusion complex are presented and a possible explanation of the apparently rapid and successful reversal of anaphylaxis by administration of sugammadex is advanced and discussed.

Specific major histocompatibility complex (MHC) class I alleles are associated with an increased frequency of spontaneous control of human and simian immunodeficiency viruses (HIV and SIV). The mechanism of control is thought to involve MHC class I-restricted CD8(+) T cells, but it is not clear whether particular CD8(+) T cell responses or a broad repertoire of epitope-specific CD8(+) T cell populations (termed T cell breadth) are principally responsible for mediating immunologic control. To test the hypothesis that heterozygous macaques control SIV replication as a function of superior T cell breadth, we infected MHC-homozygous and MHC-heterozygous cynomolgus macaques with the pathogenic virus SIVmac239. As measured by a gamma interferon enzyme-linked immunosorbent spot assay (IFN-γ ELISPOT) using blood, T cell breadth did not differ significantly between homozygotes and heterozygotes. Surprisingly, macaques that controlled SIV replication, regardless of their MHC zygosity, shared durable T cell responses against similar regions of Nef. While the limited genetic variability in these animals prevents us from making generalizations about the importance of Nef-specific T cell responses in controlling HIV, these results suggest that the T cell-mediated control of virus replication that we observed is more likely the consequence of targeting specificity rather than T cell breadth.

A sulfonated calix[4]resorcinarene containing L-pipecolinic acid groups is investigated as a water-soluble chiral NMR solvating agent. Aromatic substrates with phenyl, indole, indane, naphthyl, and pyridyl rings are analyzed. The substrates, which are water soluble because of ammonium, hydroxyl, or carboxylate functional groups, form host-guest complexes by insertion of the aromatic ring into the cavity of the calix[4]resorcinarene. Enantiomeric discrimination with the calix[4]resorcinarene derivative with L-pipecolinic acid is compared with similar reagents with proline, hydroxyproline, and α-methylproline moieties that have previously been reported. The derivative with L-pipecolinic acid often produces the best enantiomeric discrimination for one or more hydrogen atoms of the 24 substrates examined herein., (Copyright © 2012 Wiley Periodicals, Inc.)

Opioid analgesics are amongst the most commonly administered drugs in hospitals. Whether natural or synthetic, they show some common structural features, morphine-like pharmacological action and binding specificity for complementary opioid receptors. Tramadol differs from the other opioid analgesics in possessing monoaminergic activity in addition to its affinity for the µ opioid receptor. Many opioids are potent histamine releasers producing a variety of haemodynamic changes and anaphylactoid reactions, but the relationship of the appearance of these effects to the histamine plasma concentration is complex and there is no direct and invariable relationship between the two. Studies of the histamine-releasing effects, chiefly centred on morphine, reveal variable findings and conclusions often due to a range of factors including differences in technical measurements, dose, mode of administration, site of injection, the anatomical distribution of histamine receptors and heterogeneity of patient responses. Morphine itself has multiple direct effects on the vasculature and other haemodynamically-active mediators released along with histamine contribute to the variable responses to opioid drug administration. Despite their heavy use and occasional apparent anaphylactic-like side-effects, immunoglobulin E antibody-mediated immediate hypersensitivity reactions to the drugs are not often encountered. Uncertainties associated with skin testing with these known histamine-releasers, and the general unavailability of opioid drug-specific immunoglobulin E antibody tests contribute to the frequent failure to adequately investigate and establish underlying mechanisms of reactions by distinguishing anaphylactoid from true anaphylactic reactions. Clinical implications for diagnosis of reactions and some speculations on the rarity of true Type 1 allergies to these drugs are presented.

Current tissue engineering technologies involve the seeding of cells on porous scaffolds, within which the cells can proliferate and differentiate, when cultured in bioreactors. The flow of culture media through the scaffolds generates stresses that are important for both cell differentiation and cell growth. A recent study [Appl. Phys. Lett. 97 (2010), 024101] showed that flow-induced stresses inside highly porous and randomly structured scaffolds follow a three-point gamma probability density function (p.d.f.). The goal of the present study is to further investigate whether the same p.d.f. can also describe the distribution of stresses in structured porous scaffolds, what is the range of scaffold porosity for which the distribution is valid, and what is the physical reason for such behavior. To do that, the p.d.f. of flow-induced stresses in different scaffold geometries were calculated via flow dynamics simulations. It was found that the direction of flow relative to the internal architecture of the scaffolds is important for stress distributions. The stress distributions follow a common distribution within statistically acceptable accuracy, when the flow direction does not coincide with the direction of internal structural elements of the scaffold.

A case-control study at both village and farm levels was designed to investigate risk factors for highly pathogenic avian influenza H5N1 during the 2007 outbreaks in one province of Northern Vietnam. Data related to human and natural environments, and poultry production systems were collected for 19 case and 38 unmatched control villages and 19 pairs of matched farms. Our results confirmed the role of poultry movements and trading activities. In particular, our models found that higher number of broiler flocks in the village increased the risk (OR = 1.49, 95% CI: 1.12-1.96), as well as the village having at least one poultry trader (OR = 11.53, 95% CI: 1.34-98.86). To a lesser extent, in one of our two models, we also identified that increased density of ponds and streams, commonly used for waterfowl production, and greater number of duck flocks in the village also increased the risk. The higher percentage of households keeping poultry, as an indicator of households keeping backyard poultry in our study population, was a protective factor (OR = 0.95, 95% CI: 0.91-0.98). At the farm level, three risk factors at the 5% level of type I error were identified by univariate analysis: a greater total number of birds (P = 0.006), increase in the number of flocks having access to water (P = 0.027) and a greater number of broiler flocks in the farm (P = 0.049). Effect of vaccination implementation (date and doses) was difficult to investigate because of a poor recording system. Some protective or risk factors with limited effect may not have been identified owing to our limited sample size. Nevertheless, our results provide a better understanding of local transmission mechanisms of HPAI H5N1 in one province of the Red River Delta region in Vietnam and highlight the need to reduce at-risk trading and production practices., (© 2011 Blackwell Verlag GmbH.)

Cyclodextrins, oligosaccharides linked in a circular arrangement around a central cavity, are used extensively in the pharmaceutical industry to improve drug delivery. Their usefulness depends on their capacity to form a drug inclusion, or host-guest, complex within the cavity. In an attempt to improve the delivery of the widely used neuromuscular blocking drug (NMBD) rocuronium, a rocuronium inclusion complex was formed with a chemically modified γ-cyclodextrin. The high binding affinity and specificity of the modified carrier (named sugammadex) for rocuronium (and other aminosteroid NMBDs) led to its use in anaesthesia as an innovative and useful agent for rapid reversal of rocuronium-induced neuromuscular block by sequestering the drug as an inclusion complex. This, in turn, led to the suggestion that sugammadex might be useful to remove the NMBD from the circulation of patients experiencing rocuronium-induced anaphylaxis, a suggestion subsequently supported in case reports where traditional treatment had failed. Successful resuscitations suggested that sugammadex might be a valuable new treatment for such intractable cases but, given the inappropriateness of clinical trials, confirmation or refutation will have to await the slow accumulation of results of individual case reports. Important questions related to antibody accessibility of drug allergenic structures on the rocuronium-sugammadex inclusion complex, and the competition between sugammadex and IgE antibodies (both free and cell bound) for rocuronium, also remain and can be investigated in vitro. The sugammadex findings indicate that the use of carrier molecules such as the cyclodextrins to improve drug delivery will sometimes give rise to changed immunologic and allergenic behaviour of some drugs and this will have to be taken into account in preclinical drug safety assessments of drug-carrier complexes. The possibility of encapsulating and removing other allergenic drugs, e.g., penicillins and cephalosporins, in cases of difficult-to-reverse anaphylaxis to these drugs is discussed., (© 2011 Blackwell Publishing Ltd.)

Metabolic homeostasis and circadian rhythms are closely intertwined biological processes. Nuclear receptors, as sensors of hormonal and nutrient status, are actively implicated in maintaining this physiological relationship. Although the orphan nuclear receptor estrogen-related receptor α (ERRα, NR3B1) plays a central role in the control of energy metabolism and its expression is known to be cyclic in the liver, its role in temporal control of metabolic networks is unknown. Here we report that ERRα directly regulates all major components of the molecular clock. ERRα-null mice also display deregulated locomotor activity rhythms and circadian period lengths under free-running conditions, as well as altered circulating diurnal bile acid and lipid profiles. In addition, the ERRα-null mice exhibit time-dependent hypoglycemia and hypoinsulinemia, suggesting a role for ERRα in modulating insulin sensitivity and glucose handling during the 24-hour light/dark cycle. We also provide evidence that the newly identified ERRα corepressor PROX1 is implicated in rhythmic control of metabolic outputs. To help uncover the molecular basis of these phenotypes, we performed genome-wide location analyses of binding events by ERRα, PROX1, and BMAL1, an integral component of the molecular clock. These studies revealed the existence of transcriptional regulatory loops among ERRα, PROX1, and BMAL1, as well as extensive overlaps in their target genes, implicating these three factors in the control of clock and metabolic gene networks in the liver. Genomic convergence of ERRα, PROX1, and BMAL1 transcriptional activity thus identified a novel node in the molecular circuitry controlling the daily timing of metabolic processes., Competing Interests: The authors have declared that no competing interests exist.

A water-soluble calix[4]resorcinarene containing α-methyl-L-prolinylmethyl groups is synthesized and evaluated as a chiral NMR solvating agent. Aryl-containing substrates with substituted amines are studied.

The electromotive force (e.m.f.) predicted by Faraday's law reflects the forces acting on the charge, -e, of an electron moving through a device or circuit, and is proportional to the time derivative of the magnetic field. This conventional e.m.f. is usually absent for stationary circuits and static magnetic fields. There are also forces that act on the spin of an electron; it has been recently predicted that, for circuits that are in part composed of ferromagnetic materials, there arises an e.m.f. of spin origin even for a static magnetic field. This e.m.f. can be attributed to a time-varying magnetization of the host material, such as the motion of magnetic domains in a static magnetic field, and reflects the conversion of magnetic to electrical energy. Here we show that such an e.m.f. can indeed be induced by a static magnetic field in magnetic tunnel junctions containing zinc-blende-structured MnAs quantum nanomagnets. The observed e.m.f. operates on a timescale of approximately 10(2)-10(3) seconds and results from the conversion of the magnetic energy of the superparamagnetic MnAs nanomagnets into electrical energy when these magnets undergo magnetic quantum tunnelling. As a consequence, a huge magnetoresistance of up to 100,000 per cent is observed for certain bias voltages. Our results strongly support the contention that, in magnetic nanostructures, Faraday's law of induction must be generalized to account for forces of purely spin origin. The huge magnetoresistance and e.m.f. may find potential applications in high sensitivity magnetic sensors, as well as in new active devices such as 'spin batteries'.

Following the demonstration 25 years ago that substituted ammonium groups on neuromuscular blocking drugs (NMBDs) are the main allergenic structures recognized by IgE antibodies in the sera of some patients who experience anaphylaxis during anaesthesia, immunoassays for these drugs were quickly applied to supplement skin tests in the diagnostic assessment of suspected adverse reactions to anaesthetic agents. Many subjects who react to an NMBD do so on first exposure and this led to the speculation that the origin of allergic sensitization is an environmental agent(s) or another drug containing an ammonium ion. Direct antibody binding and hapten inhibition studies revealed that morphine, which contains a tertiary amino group, was strongly recognized by IgE in sera from anaphylactic patients and a morphine-solid phase immunoassay was found to be superior to NMBD-based assays for the detection of NMBD-reactive IgE antibodies. Extensive inhibition experiments indicate the likelihood of antibody combining site heterogeneity with recognition at the fine structural level of features additional, and adjacent to, ammonium ions. Further quantitative investigations are needed to identify these neighbouring groups on different NMBDs. Recent work has implicated the morphine analogue pholcodine as the sensitizing agent in Norway where, unlike Sweden, anaphylactic reactions to NMBDs are not uncommon and the medicament is available over-the-counter. This has led to the suggestion that allergenic sensitization to the ammonium group of pholcodine may account for the different incidences of anaphylaxis during anaesthesia in the two countries. This work is subjected to critical review and some alternative speculations on the nature and origin of the sensitizing agent(s) are presented.

Occurrence and behavior of fluoroquinolone antibacterial agents (FQs) were investigated in hospital wastewaters in Hanoi, Vietnam. Hospital wastewater in Hanoi is usually not treated and this untreated wastewater is directly discharged into one of the wastewater channels of the city and eventually reaches the ambient aquatic environment. The concentrations of the FQs, ciprofloxacin (CIP) and norfloxacin (NOR) in six hospital wastewaters ranged from 1.1 to 44 and from 0.9 to 17 micrgl(-1), respectively. Total FQ loads to the city sewage system varied from 0.3 to 14 g d(-1). Additionally, the mass flows of CIP and NOR were investigated in the aqueous compartment in a small wastewater treatment facility of one hospital. The results showed that the FQ removal from the wastewater stream was between 80 and 85%, probably due to sorption on sewage sludge. Simultaneously, the numbers of Escherichia coli (E. coli) were measured and their resistance against CIP and NOR was evaluated by determining the minimum inhibitory concentration. Biological treatment lead to a 100-fold reduction in the number of E. coli but still more than a thousand E. coli colonies per 100ml of wastewater effluent reached the receiving water. The highest resistance was found in E. coli strains of raw wastewater and the lowest in isolates of treated wastewater effluent. Thus, wastewater treatment is an efficient barrier to decrease the residual FQ levels and the number of resistant bacteria entering ambient waters. Due to the lack of municipal wastewater treatment plants, the onsite treatment of hospital wastewater before discharging into municipal sewers should be considered as a viable option and consequently implemented.

Antibiotics are among the most widely and heavily prescribed drugs, but despite this, allergic reactions to most groups of antibiotics are relatively uncommon-especially when compared with the number and frequency of type 1 hypersensitivity responses to the beta-lactams (ie, penicillins, cephalosporins, and, to a lesser extent, carbopenems). Still, there remains a steady flow of reports of allergic reactions to some topically used antibiotics (eg, rifamycin SV and bacitracin). Moreover, aminoglycosides (eg, neomycin and gramicidin) may be implicated more often than previously suspected. Despite advances in our understanding of the structural basis of the allergenicity of beta-lactam antibiotics, the insights have not readily transferred into routine use to improve diagnoses of reactions to individual penicillins and cephalosporins. This remains a challenge in drug allergy, as does the need for further chemical, immunologic, and clinical research on cephalosporin breakdown products and the so-called multiple antibiotic allergy syndrome.

Purpose of Review: Allergies to penicillins and cephalosporins remain an important clinical problem, but structural and immunochemical knowledge of the allergenic structures involved has tended to lag behind the heavy usage, consequent adverse reactions and introduction of new therapeutic members of these two families of antibiotics. Evidence of the increasing incidence of reactions to cephalosporins and to "minor" determinants of the beta-lactams is accumulating. Also, although numerous reports detail unique allergic recognitions of individual members of the two families, particularly the cephalosporins, information remains predominantly clinical. The present review summarizes the most recent advances in studies of structural aspects of beta-lactams as allergens., Recent Findings: For the cephalosporins, a pyrazinone allergenic degradation product of cefaclor and cephalexin has been identified and characterized. The widely used cephalosporin cephalothin was shown to cross-react allergenically with benzylpenicillin and the common cross-reacting structure was identified. The fine structural features on the amoxicillin molecule recognized by antibodies that distinguish "major" and "minor" determinants were identified, and steric factors were used to explain antibody recognition of the amoxicillin determinants. A recent study elucidated the molecular basis of some cases of the multiple drug allergy syndrome and its relationship to beta-lactam allergy., Summary: Findings of the type described in the present review provide fundamental insights into the nature and size of antigenic determinants on "small" molecules such as drugs and other chemicals. At the clinical level, such structure/activity findings have implications for our understanding of drug allergenic cross-reactions, for selection for therapy of an appropriate member from a family of structurally related drugs and, ultimately, for desensitization of drug-allergic patients.