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Aim The current study was conducted to determine the antimicrobial resistance profile and genetic relatedness of Aeromonas sp. isolated from healthcare and urban effluents, wastewater treatment plant (WWTP) and river water. Methods and results We detected the presence of genes conferring resistance to β-lactam, quinolone and aminoglycoside. Multilocus sequence typing was carried out to differentiate the strains, and multilocus phylogenetic analysis was used to identify the species. A total of 28 cefotaxime-resistant Aeromonas sp. strains were identified, harbouring uncommon Guiana-extended-spectrum (GES)-type β-lactamases (GES-1, GES-5, GES-7 and GES-16). Multidrug-resistant Aeromonas sp. were found in hospital wastewater, WWTP and sanitary effluent, and A. caviae was identified as the most prevalent species (85·7%). Conclusion The release of untreated healthcare effluents, presence of antimicrobials in the environment, in addition to multidrug-resistant Aeromonas sp., are all potential factors for the spread of resistance. Significance and impact of the study We identified a vast repertoire of antimicrobial resistance genes (ARG) in Aeromonas sp. from diverse aquatic ecosystems, including those that encode enzymes degrading broad-spectrum antimicrobials widely used to treat healthcare-associated infections. Hospital and sanitary effluents serve as potential sources of bacteria harbouring ARG and are a threat to public health.

We investigated the anaerobic degradation of tetracycline antibiotics (tetracycline [TC], oxytetracycline [OTC] and chlortetracycline [CTC]) in swine, cattle, and poultry manures. The manures were anaerobically digested inside polyvinyl chloride batch reactors for 64 days at room temperature. The degradation rate constants and half-lives of the parent tetracyclines were determined following first-order kinetics. For CTC the fastest degradation rate was observed in swine manure (k = 0.016 ± 0.001 d

We developed a novel optical sensor for sensitive and selective detection of catecholamines based on upconversion nanoparticles (UCNPs) decorated with different metal ions (UCNP-Men+). 1,2-ethanedithiol was chosen as a surface additive to synthesize the NaLuGdF4:Yb3+/Er3+ UCNPs by one-step at 200 °C. The as-prepared UCNPs exhibited a strong emission under the continuous excitation at 980 nm. It was found that catecholamines could be more effectively detected in the presence of UCNP-Fe3+, whereas, dopamine and epinephrine were detected selectively using UCNP-Li+ and UCNP-Cu2+ sensors, respectively. Under the optimum conditions, the limit of detections (LODs) for catecholamines, dopamine, and epinephrine are 2.8, 2.5, and 2.4 nM, respectively, with good linearity in the range of 5–320 nM for total catecholamines and 5–30 nM for dopamine and epinephrine. The developed method has been successfully applied to detect dopamine and epinephrine in human urine samples with good accuracy and satisfactory recovery.

The results of Fourier Transform Infrared absorption and Raman spectroscopy studies are reported for solid and liquid neat butane-1,4-diamine (DAB) and for the molecule in different solvents. Ab initio molecular dynamics and static calculations are reported in the work as an interpretative tool for the measurements and provide an analysis of the relative population of DAB conformers, both in vacuo and in the liquid phase. X-ray diffraction data for liquid DAB are presented to further consolidate the interpretation of the conformation and structure of the biomolecule in the liquid phase. The study of DAB in polar solutions suggests a high level of structuring of the molecules in the liquid, as a consequence of the effect of solvent on the molecular charge distribution.

Background: the lack of standardized pathways for patients with gastrointestinal bleeding may have led to differences in their management and inequity to medical care access. The "Hub & Spoke" model was adopted to fill this gap in many disciplines, but, to our knowledge, no data exist on its efficacy on mortality in GI bleeding. We aimed to evaluate if the "Hub & Spoke" organizational model has an impact on mortality risk from UGIB. Methods: from January 2014 to December 2015, 3324 consecutive patients admitted for UGIB in 50 Italian hospitals were enrolled (1977 patients in hospitals within the "Hub & Spoke" network for digestive hemorrhagic emergency and 1347 in hospitals outside the "Hub & Spoke" network). Clinical, endoscopic and organizational data were recorded. Results: we observed no differences in mortality between patients admitted to hospitals included or not included in the "Hub & Spoke" network (5.2% vs 6.1%, p = 0.3). On multivariate analysis, admission in gastroenterology wards (OR 0.61, p = 0.001) or an academic hospital (OR 0.65, p < 0.056) were independent protective factors while being in "Hub & Spoke" organization system did not affect mortality (OR 1.09, p = 0.57). Conclusion: the "Hub & Spoke" model per sé does not impact on mortality while being treated in academic hospital or gastroenterology wards improved survival.

Anaerobic digestion is used for the treatment of animal manure by generating biogas. Heavy metals cause environmental pollutions and co-select for antimicrobial resistance. We evaluated the impact of mesophilic anaerobic digestion of cattle manure (CM), swine manure (SM) and poultry litter (PL) on the concentrations of seven tetracycline [tet(A), tet(B), tet(G), tet(M), tet(O), tet(Q), and tet(W)], macrolide [erm(B)], methicillin (mecA and mecC), copper (copB, pcoA, pcoD, and tcrB) and zinc (czrC) resistance genes, and three bacterial species (E. coli, Enterococcus spp. and Staphylococcus aureus). The total bacterial population and total abundance of the seven tet genes significantly increased in the three manure types after digestion. Concentration of tet(M) was strongly correlated with that of erm(B) and enterococci. As concentration of tetracyclines declined during anaerobic digestion, that of four tet genes (A, B, Q, and W) and 16S rRNA increased, that of tet(M) decreased, and that of tet(G) and tet(O) did not change. Concentrations of copB and pcoA did not change; while that of pcoD did not change in the PL, it increased in the SM and CM. While the concentration of enterococci remained unchanged in CM, it significantly increased in the PL and SM. Concentrations of tcrB significantly increased in the three manure types. While concentrations of S. aureus significantly increased in the CM and PL, that of SM was not affected. Concentrations of mecC significantly increased in all manure types after digestion; while mecA concentrations did not change in the SM, they significantly increased in CM and PL. While concentration of czrC remained low in the CM, it increased in the PL but declined in the SM. In conclusion, while mesophilic anaerobic digestion of animal manure decreased concentration of tetracyclines, it increased the concentrations of total bacteria, tet genes, E. coli, enterococci and S. aureus and methicillin resistance genes. It did not have any effect on concentrations of heavy metals; concentrations of heavy metal resistance genes either increased or remained unaffected depending on the animal species. This study showed the need for post-digestion treatments of animal manure to remove bacteria, antibiotic resistance genes, heavy metals and their resistance genes.

The bis(imino)pyridine iron complex, for the first time, is developed as an effective metal carbene catalyst for carbene transfer reactions of donor-acceptor diazo compounds. Its broad catalytic capability is demonstrated by a range of metal carbene reactions, from cyclopropanation, cyclopropenation, epoxidation, and Doyle-Kirmse reaction to O-H insertion, N-H insertion, and C-H insertion reactions. The asymmetric cyclopropanation of styrene and methyl phenyldiazoacetate was successfully achieved by the new chiral bis(imino)pyridine iron catalyst, which delivers a new gateway for the development of chiral iron catalysis for metal carbene reactions.

The impact of anaerobic digestion of animal waste on the persistence of antibiotic resistance genes (ARGs) and antibiotics is not widely studied. Two identical, 800-L digesters seeded with swine slurry were followed up to 100 d in three separate trials. The trials received varying amounts of antibiotic-free corn ( L.) mixed with water to maintain the digestion process. Biogas production, seven tetracycline resistance () genes, and three tetracyclines and their transformation products were measured. Biogas production proportionally increased as the feeding loads increased between trials. In Trial 1, log gene copies showed small but statistically significant (0.01) increases during digestion. In Trial 2, anaerobic digestion did not have a significant (0.05) effect except for significant reductions in B (0.0001) and G ( = 0.0335) log gene copies. In Trial 3, which received the highest amount of corn mix, log copies of the 16S ribosomal RNA and the genes significantly (0.0001) reduced over time during digestion. Up to 36 μg L tetracycline, 112 μg L chlortetracycline, 11.9 mg L isochlortetracycline, and 30 μg L 4-epitetracycline were detected both in the liquid and solid digestates. Results of this study revealed that although anaerobic digestion of swine waste can produce useful biogas, it does not result in complete removal of bacteria, ARGs, and antibiotics regardless of differences in the feeding loads between trials. Further effluent and sludge treatments are required prior to their downstream use in crop production to minimize emergence and environmental dissemination of antimicrobial-resistant bacteria through animal manure.

Upconversion nanoparticles (UCNPs) possess a unique type of photoluminescence (PL) in which lower-energy excitation is converted into higher-energy emission via multi-photon absorption processes. In this work, we have used a facile one-step hydrothermal method promoted water solubility to synthesis NaLuGdF4:Yb3 +/Er3 +(Tm3 +) UCNPs coated with malonic acid (MA). Scanning electron microscopy images and X-ray diffraction patterns reveal sphere-shaped UCNPs with an average size of ~ 80 nm crystallized in the cubic NaLuF4 structure. The characteristic vibrations of cubic UCNPs have been taken into account by using Fourier-transform infrared spectroscopy. Based on PL studies, we have determined an optimal concentration of Gd3 + doping. The dependence of upconversion PL intensity on Gd3 + concentration is discussed via the results of magnetization measurements, which is related to the coupling/uncoupling of Gd3 + ions. Particularly, our study reveals that carboxyl-functionalized NaLuGdF4:Yb3 +/Er3 +(Tm3 +) UCNPs have a relatively high cell viability with HeLa cells.

A new approach with simple, fast and most versatile at low synthetic temperature is proposed for producing carbon nitride nanoparticles using ammonium citrate as both the nitrogen source and the framework for the formation of carbon nitride via solid state reaction. The prepared products are water soluble with high quantum yields of 27%. The initial assessments for optosensing of mercury ions and bisphenol A were performed based on the change in fluorescent intensity of the developed product. The mercury ions could be detected with a limit of detection of 60 nM with high selectivity based on the quenching effect. The detection on Bisphenol-A was carried out using “off-on” technique of fluorescent intensity with a limit of detection of 45 nM.

Summary This study aimed to investigate the effect of physical fitness level (Yo-Yo intermittent recovery test level 1 [Yo-Yo IR 1]) and initial stress level (salivary cortisol [SC]) on salivary immunoglobulin A secretion rate (SIgArate), and the influence of physical fitness on accelerations (external training load; eTL) and training impulse (TRIMP; internal training load; iTL), in 20 elite youth male basketball players (14.5 ± 0.5 years; height, 177 ± 10 cm; body mass, 69 ± 13 kg) following a short-term training stress (two daily consecutive basketball-training sessions). Saliva samples were collected before and after the experimental period. A multiple linear regression analysis was conducted using the Yo-Yo IR 1 and SC as independent variables, and changes in SIgArate as dependent variable. The Yo-Yo IR 1 was the only statistically significant variable (R = 0.73; P = 0.001). Participants were divided a posteriori into high fitness (HFG) and low fitness (LFG) groups according to the median-split technique, taking the Yo-Yo IR 1 performance into account, to compare the eTL and iTL. HFG performed a higher total eTL (34 ± 13 vs. 17 ± 7 accelerations; t = 3.4; P = 0.003) but no difference between fitness groups was observed for TRIMP (t = 0.33; P = 0.74). The results suggest that physical fitness level may play a role on mucosal immunity responses from short-term training stress in youth basketball players. Players with greater level of physical fitness are likely to perform a higher training load without inducing higher stress levels.

An electrically controlled and renewable hydrophobic surface used to trap and release three test pollutants on an indium-tin-oxide (ITO) electrode is presented. Oxygen plasma was used to maximize the activated hydroxyl groups on the ITO surface, which were reacted with (3-aminopropyl) triethoxysilane (APTES) to create a 3-amino propyl layer. Copper(II) ions were introduced and attached to the terminal amine groups. The amine group from 1-hexadecylamine (HDA), complexed the surface-confined copper(II) ions, which resulted in terminal hexadecyl alkyl groups. The created hydrophobic surface was tested for its ability to adsorb pollutant substances, namely bisphenol-A, 2-naphthol, and doxepin. Desorption was accomplished by reducing copper(II) to copper(0) electrochemically. This led to the weakening of the metal-amine complex and the concomitant detachment of the HDA and trapped species from the ITO surface. Efficient trapping and releasing of bisphenol-A (1 ppm) was achieved with around 84% adsorption, 100% desorption (in a time course of less than 30 s), and 42-fold enrichment on the concentration. After each adsorption/desorption trial, regeneration of the hydrophobic surface was achieved by reapplication of copper(II) ions and HDA. Five cycles were successfully repeated without any significant deterioration in performance. Similar trap-and-release performance was also attained for 2-naphthol and doxepin.

Purpose Adjuvant chemotherapy improves survival of patients with gastric cancer. Intergroup Trial of Adjuvant Chemotherapy in Adenocarcinoma of the Stomach (ITACA-S) was a phase III study comparing sequential FOLFIRI followed by docetaxel/cisplatin versus 5-fluorouracil monotherapy. The intensive regimen was not superior in terms of disease-free survival (DFS) and overall survival (OS). Methods The treatment was to be started within 8 weeks from surgery. This analysis evaluates the impact of time from surgery to chemotherapy start (TSC) on outcomes. Results Out of 1,106 randomized, 1,072 patients without major violations of eligibility criteria and receiving at least one treatment cycle were analyzed. Median TSC was 50 days. Chemotherapy was interrupted in 201 (18.8%) cases, whereas it was completed without or with modifications in 277 (25.8%) and 594 (55.4%), respectively. At a median follow-up of 56.9 months, 513 progressions and 472 deaths occurred. A longer TSC was significantly associated with longer DFS (hazard ratio [HR] 0.95; 95% confidence interval [CI] 0.89-1.00; p = 0.05) and OS (HR 0.91; 95% CI 0.86-0.97; p = 0.004), after adjustment for treatment arm, age, sex, primary tumor site, number of resected nodes, and tumor stage. Better treatment compliance was associated with improved survival. Conclusions Our findings suggest that longer TSC had at least no detrimental effect on DFS and OS, whereas treatment completion had a protective effect. Our findings need to be confirmed prospectively.

We report a promising simple strategy for improving the performance of the photoanode for photoelectrochemical (PEC) water splitting. ZnO nanorods on an indium tin oxide glass substrate were synthesized by a hydrothermal method following calcinations in air at 500 °C for 2 h and pure ambient hydrogen at atmospheric pressure at 400 °C for 30 min. The hydrogenated ZnO (H:ZnO) sample shows an enhanced photocurrent in comparison to that of ZnO nanorods. To enhance the absorption in the visible light and near-infrared regions, H:ZnO nanorods were sensitized by cadmium sulfide (CdS) nanoparticles and carbon quantum dots (CQDs). The H:ZnO nanorod film sensitized in this way exhibited significantly improved PEC properties after treatment with ambient nitrogen at 400 °C for 30 min. The optimized H:ZnO nanorod sample sensitized by CdS and CQDs yields a photocurrent density of ∼12.82 mA/cm2 at 0 V (vs saturated calomel electrode (SCE)) in 0.25 M Na2S and 0.35 M Na2SO3 solution under the illumination of simulated sol...

Key points Loss-of-function mutations of the skeletal muscle ClC-1 channel cause myotonia congenita with variable phenotypes. Using patch clamp we show that F484L, located in the conducting pore, probably induces mild dominant myotonia by right-shifting the slow gating of ClC-1 channel, without exerting a dominant-negative effect on the wild-type (WT) subunit. Molecular dynamics simulations suggest that F484L affects the slow gate by increasing the frequency and the stability of H-bond formation between E232 in helix F and Y578 in helix R. Three other myotonic ClC-1 mutations are shown to produce distinct effects on channel function: L198P shifts the slow gate to positive potentials, V640G reduces channel activity, while L628P displays a WT-like behaviour (electrophysiology data only). Our results provide novel insight into the molecular mechanisms underlying normal and altered ClC-1 function. Abstract Myotonia congenita is an inherited disease caused by loss-of-function mutations of the skeletal muscle ClC-1 chloride channel, characterized by impaired muscle relaxation after contraction and stiffness. In the present study, we provided an in-depth characterization of F484L, a mutation previously identified in dominant myotonia, in order to define the genotype–phenotype correlation, and to elucidate the contribution of this pore residue to the mechanisms of ClC-1 gating. Patch-clamp recordings showed that F484L reduced chloride currents at every tested potential and dramatically right-shifted the voltage dependence of slow gating, thus contributing to the mild clinical phenotype of affected heterozygote carriers. Unlike dominant mutations located at the dimer interface, no dominant-negative effect was observed when F484L mutant subunits were co-expressed with wild type. Molecular dynamics simulations further revealed that F484L affected the slow gate by increasing the frequency and stability of the H-bond formation between the pore residue E232 and the R helix residue Y578. In addition, using patch-clamp electrophysiology, we characterized three other myotonic ClC-1 mutations. We proved that the dominant L198P mutation in the channel pore also right-shifted the voltage dependence of slow gating, recapitulating mild myotonia. The recessive V640G mutant drastically reduced channel function, which probably accounts for myotonia. In contrast, the recessive L628P mutant produced currents very similar to wild type, suggesting that the occurrence of the compound truncating mutation (Q812X) or other muscle-specific mechanisms accounted for the severe symptoms observed in this family. Our results provide novel insight into the molecular mechanisms underlying normal and altered ClC-1 function.

Iron cobalt oxides, such as typical FeCo2O4 and CoFe2O4, are two spinel structured transitional metal oxide materials with excellent electrochemical performance. As the electrodes, they have been widely applied in the current energy storage and conversion processes such as supercapacitors, Lithium-ion batteries and fuel cells. Based on synthesis approaches and controlled conditions, these two materials exhibited broad morphologies and nanostructures and thus distinct electrochemical performance. Some of them have shown promising applications as electrodes in energy storage and conversion. The incorporation with other materials to form composites further improved their performance. This review briefly summarized the recent applications of FeCo2O4 and CoFe2O4 in energy storage and conversion, current understandings on mechanisms and especially the relevance of morphologies and structures and composites to electrochemical performance. Some recommendations were finally put forward addressing current issues and future prospects on electrodes of FeCo2O4 and CoFe2O4 based materials in energy storage and conversion, implying there was still space to further optimize their performance.

BACKGROUND AND PURPOSE: Although chloride channels are involved in several physiological processes and acquired diseases, the availability of compounds selectively targeting CLC proteins is limited. ClC‐1 channels are responsible for sarcolemma repolarization after an action potential in skeletal muscle and have been associated with myotonia congenita and myotonic dystrophy as well as with other muscular physiopathological conditions. To date only a few ClC‐1 blockers have been discovered, such as anthracene‐9‐carboxylic acid (9‐AC) and niflumic acid (NFA), whereas no activator exists. The absence of a ClC‐1 structure and the limited information regarding the binding pockets in CLC channels hamper the identification of improved modulators. EXPERIMENTAL APPROACH: Here we provide an in‐depth characterization of drug binding pockets in ClC‐1 through an integrated in silico and experimental approach. We first searched putative cavities in a homology model of ClC‐1 built upon an eukaryotic CLC crystal structure, and then validated in silico data by measuring the blocking ability of 9‐AC and NFA on mutant ClC‐1 channels expressed in HEK 293 cells. KEY RESULTS: We identified four putative binding cavities in ClC‐1. 9‐AC appears to interact with residues K231, R421 and F484 within the channel pore. We also identified one preferential binding cavity for NFA and propose R421 and F484 as critical residues. CONCLUSIONS AND IMPLICATIONS: This study represents the first effort to delineate the binding sites of ClC‐1. This information is fundamental to discover compounds useful in the treatment of ClC‐1‐associated dysfunctions and might represent a starting point for specifically targeting other CLC proteins.

Upconversion nanoparticles (UCNPs) possess a unique type of photoluminescence (PL) in which lower-energy excitation is converted into higher-energy emission via multi-photon absorption processes. In this work, we have used a facile one-step hydrothermal method promoted water solubility to synthesis NaLuGdF

Aim Notwithstanding the widely accepted idea that following disuse skeletal muscles become faster, an increase in shortening velocity was previously observed mostly in fibres containing type 1 myosin, whereas a decrease was generally found in fibres containing type 2B myosin. In this study, unloaded shortening velocity of pure type 1 and 2B fibres from hindlimb unloaded mice was determined and a decrease in type 2B fibres was found. Methods To clarify whether the decrease in shortening velocity could depend on alterations of myosin motor function, an in vitro motility assay approach was applied to study pure type 1 and pure type 2B myosin from hindlimb unloaded mice. The latter approach, assessing actin sliding velocity on isolated myosin in the absence of other myofibrillar proteins, enabled to directly investigate myosin motor function. Results Actin sliding velocity was significantly lower on type 2B myosin following unloading (2.70 ± 0.32 μm s−1) than in control conditions (4.11 ± 0.35 μm s−1), whereas actin sliding velocity of type 1 myosin was not different following unloading (0.89 ± 0.04 μm s−1) compared with control conditions (0.84 ± 0.17 μm s−1). Myosin light chain (MLC) isoform composition of type 2B myosin from hindlimb unloaded and control mice was not different. No oxidation of either type 1 or 2B myosin was observed. Higher phosphorylation of regulatory MLC in type 2B myosin after unloading was found. Conclusion Results suggest that the observed lower shortening velocity of type 2B fibres following unloading could be related to slowing of acto-myosin kinetics in the presence of MLC phosphorylation.

The diagnostic research process can be divided into five phases, designed to establish the clinical utility of a new diagnostic test—the index test. The aim of the present review is to illustrate the study designs that are appropriate for each diagnostic phase, using clinical examples regarding liver fibrosis diagnosed with transient elastography, when possible. Phase 0 is the preclinical pilot phase during which the validity, reliability, and reproducibility of the index test are assessed in healthy and diseased people. Phase I is designed to describe the distribution of the index test results in healthy people and its normal values. Phase IIA comprises studies designed to estimate the accuracy (sensitivity and specificity) of the index test in discriminating between diseased and nondiseased people in a clinically relevant population. Phase IIB studies allow the comparison of the accuracy of different index tests; Phase IIC studies aim to evaluate the possible harms of incorporating the index test in a diagnostic-therapeutic strategy. In phase III, diagnostic test-therapeutic randomized clinical trials aim to assess the benefits and harms of the new diagnostic-therapeutic strategy versus the present strategy. Phase IV comprises large surveillance cohort studies that aim to assess the effectiveness of the new diagnostic-therapeutic strategy in clinical practice. Conclusion: As common in clinical research, giving excessive weight to the results of single studies and trials is likely to divert from the totality of evidence obtained through the systematic reviews of these studies, conducted with rigorous methodology and statistical methods. (Hepatology 2014;60:408-418)

The use of plant-based biosorbents for removing environmental pollutants from water is gaining widespread attention. In this paper, the 45–250 μm biosorbents were prepared from the husks of water bamboo (Zizania caduciflora Turcz.), with a pore size distribution of 5.7–13.8 nm and surface area of 1.87 m2/g. These water bamboo husk particles contained OH and COOH groups and had a zero point of charge between pH 2 and 3. An optimal negative charge on particle surface was achieved at pH 5. Moreover, their cation exchange capacity was about 1.3 meq/g. When trapping metal ions at pH 5, the prepared biosorbents exhibited strong affinity to Cu2 +, Cr3 +, Pb2 +, and Fe3 +. Adsorption isotherms and breakthrough studies were generated for Fe3 + (stronger affinity) and Ni2 + (weaker affinity), and the interpretation of results indicated that the water bamboo husk particles are well suited to trap these ions at low concentrations. Also, column trapping of metal ions (breakthrough volume: 75 bed volume for Ni2 + and 90 bed volume for Fe3 +) proved much more efficient than static adsorption.