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• Sodium thiosulfate (STS) increased sulfated polysaccharides (ST-SPS) yields of fungus. • Sodium thiosulfate enhanced the sulfate content of ST-SPS. • Low-molecular-weight ST-SPSs (< 20 kDa) covered almost half of the ST-SPSs mixture. • ST-SPS downregulated EGFR signaling pathways. • ST-SPS enhanced synergistically clinical drugs-induced cytotoxic effects. Sulfated polysaccharides (SPSs) are polysaccharides (PSs) with high sulfate functionalization and possess bioactivities. This study aimed to increase the sulfate content of SPSs in Antrodia cinnamomea through sulfate feeding. Feeding A. cinnamomea with sodium thiosulfate was found to increase yields of PSs and SPSs in A. cinnamomea. The SPSs thus obtained (ST-SPS) were further isolated, showing enhanced sulfate content of 2.5 mmol/g. Sodium thiosulfate induced changes in molecular weight from 320 kDa to 1342 kDa, and area percentage of low-molecular-weight ST-SPS (< 20 kDa) was decreased. Functional studies revealed that sodium thiosulfate increased the ST-SPS anticancer efficacy in cancer cells via inhibition of EGFR/AKT signaling. Moreover, the ST-SPS enhanced synergistically cisplatin-, gefitinib- and 5 FU-induced cytotoxic effects in lung cancer H1975 cells and colon cancer CT26 cells. This study is the first to demonstrate that sodium thiosulfate induced changes in properties of A. cinnamomea with the anticancer mechanisms of ST-SPS. [ABSTRACT FROM AUTHOR]

Objectives: Our aim was to determine the antimicrobial susceptibilities of 2862 Listeria monocytogenes cultured from various foods in China and to use WGS to characterize the antimicrobial resistance and virulence genotypes of those expressing a resistance phenotype.Methods: The susceptibilities of 2862 L. monocytogenes were determined by broth microdilution. Twenty-eight L. monocytogenes were found to be resistant to one to four antibiotics. All 28 resistant isolates were subsequently sequenced using short-read high accuracy protocols. The corresponding genomes were assembled and further analysis was carried out using appropriate bioinformatics pipelines.Results: All 28 resistant L. monocytogenes were classified into five STs (ST3, ST8, ST9, ST155 and ST515). Both ST9 and ST155 were dominant and their genotypes correlated with their resistance phenotypes. All ST9 isolates were MDR and could be phylogenetically classified into two clusters. One was relatively close to clinical origins and one to food. Downstream analysis of the genetic contexts in which these resistance genotypes were found suggested that these may have been acquired from other bacteria by horizontal transfer or insertion into the chromosome. All isolates harboured Listeria pathogenicity island (LIPI)-1 and LIPI-2, and only two harboured LIPI-3.Conclusions: This study reported on the antimicrobial susceptibilities of 2862 foodborne L. monocytogenes along with the genomic characterization of 28 resistant isolates, 11 of which expressed an MDR phenotype. These data showed that this bacterium can acquire resistance by horizontal gene transfer in and between species. This study may necessitate a re-evaluation of risk to public health, associated with this bacterial species. [ABSTRACT FROM AUTHOR]

Objectives: The prevalence of infections caused by OXA-48-like carbapenemase-producing organisms in Ireland has increased dramatically since 2011 and is an urgent public health issue. Genome-based high-resolution genotyping was used to analyse clinical isolates submitted to the Irish Carbapenemase-Producing Enterobacteriaceae Reference Laboratory Service for a 13 month period (2016-17).Methods: A total of 109 OXA-48-producing non-duplicate clinical isolates from 16 submitting centres were sequenced. Using a gene-by-gene approach, isolate genomes were characterized by MLST and core genome MLST, and the presence of antimicrobial resistance determinants was determined. Reference mapping and a novel plasmid MLST-type approach was applied to determine plasmid background.Results: The OXA-48-like-producing isolates were Escherichia coli (n = 56), Klebsiella spp. (n = 46) and Enterobacter cloacae (n = 7). Amongst the E. coli isolates there were 37 different STs and amongst the Klebsiella spp. isolates there were 27 different STs. blaOXA-48 was present in 105/109 (96.3%) of isolates. Based on mapping analysis and detection of the pOXA-48 IncL-type plasmid replicon and backbone genes, a pOXA-48-like plasmid was identified in 93/109 isolates (85.3%). The remaining isolates (n = 16; 14.7%) harboured blaOXA-48-like genes in unknown environments. Using a gene-by-gene approach two pOXA-48-like plasmid groups with 2/71 pOXA-48-like locus differences between them were identified.Conclusions: In Ireland we found a diversity of genotypes associated with OXA-48-like-producing clinical isolates with the IncL pOXA-48 plasmid type predominating as the blaOXA-48 genetic environment. A plasmid MLST approach can rapidly identify plasmids associated with outbreaks and monitor spread of types temporally and geographically. [ABSTRACT FROM AUTHOR]

Background: Middle ear (intratympanic, IT) administration is a promising therapeutic method as it offers the possibility of achieving high inner ear drug concentrations with low systemic levels, thus minimizing the risk of systemic side effects and drug-drug interactions. Premature elimination through the Eustachian tube may be reduced by stabilizing drug solutions with a hydrogel, but this raises the secondary issue of conductive hearing loss. Aim: This study aimed to investigate the properties of a chitosan-based particulate hydrogel formulation when used as a drug carrier for IT administration in an in vivo model of ototoxicity. Materials and Methods: Two particulate chitosan-based IT delivery systems, Thio-25 and Thio-40, were investigated in albino guinea pigs (n = 94). Both contained the hearing protecting drug candidate sodium thiosulfate with different concentrations of chitosan gel particles (25% vs. 40%). The safety of the two systems was explored in vivo. The most promising system was then tested in guinea pigs subjected to a single intravenous injection with the anticancer drug cisplatin (8 mg/kg b.w.), which has ototoxic side effects. Hearing status was evaluated with acoustically evoked frequency-specific auditory brainstem response (ABR) and hair cell counting. Finally, in vivo magnetic resonance imaging was used to study the distribution and elimination of the chitosan-based system from the middle ear cavity in comparison to a hyaluronan-based system. Results: Both chitosan-based IT delivery systems caused ABR threshold elevations (p < 0.05) that remained after 10 days (p < 0.05) without evidence of hair cell loss, although the elevation induced by Thio-25 was significantly lower than for Thio-40 (p < 0.05). Thio-25 significantly reduced cisplatin-induced ABR threshold elevations (p < 0.05) and outer hair cell loss (p < 0.05). IT injection of the chitosan- and hyaluronan-based systems filled up most of the middle ear space. There were no significant differences between the systems in terms of distribution and elimination. Conclusion: Particulate chitosan is a promising drug carrier for IT administration. Future studies should assess whether the physical properties of this technique allow for a smaller injection volume that would reduce conductive hearing loss. [ABSTRACT FROM AUTHOR]

Background: Reliable phenotypic antimicrobial susceptibility testing can be a challenge in clinical settings in low- and middle-income countries. WGS is a promising approach to enhance current capabilities.Aim: To study diversity and resistance determinants and to predict and compare resistance patterns from WGS data of Acinetobacter baumannii with phenotypic results from classical microbiological testing at a tertiary care hospital in Tanzania.Methods and Results: MLST using Pasteur/Oxford schemes yielded eight different STs from each scheme. Of the eight, two STs were identified to be global clones 1 (n = 4) and 2 (n = 1) as per the Pasteur scheme. Resistance testing using classical microbiology determined between 50% and 92.9% resistance across all drugs. Percentage agreement between phenotypic and genotypic prediction of resistance ranged between 57.1% and 100%, with coefficient of agreement (κ) between 0.05 and 1. Seven isolates harboured mutations at significant loci (S81L in gyrA and S84L in parC). A number of novel plasmids were detected, including pKCRI-309C-1 (219000 bp) carrying 10 resistance genes, pKCRI-43-1 (34935 bp) carrying two resistance genes and pKCRI-49-1 (11681 bp) and pKCRI-28-1 (29606 bp), each carrying three resistance genes. New ampC alleles detected included ampC-69, ampC-70 and ampC-71. Global clone 1 and 2 isolates were found to harbour ISAba1 directly upstream of the ampC gene. Finally, SNP-based phylogenetic analysis of the A. baumannii isolates revealed closely related isolates in three clusters.Conclusions: The validity of the use of WGS in the prediction of phenotypic resistance can be appreciated, but at this stage is not sufficient for it to replace conventional antimicrobial susceptibility testing in our setting. [ABSTRACT FROM AUTHOR]

Objectives: To describe the epidemiological trend of linezolid-resistant enterococci (LRE) collected in France from 2006 to 2016 and to extensively characterize LRE isolates.Methods: The National Reference Center for Enterococci (NRC-Enc) received enterococcal isolates suspected to be VRE and/or LRE from all French hospitals between 2006 and 2016. LRE isolates were phenotypically characterized and their genomes were entirely sequenced by Miseq (Illumina). Transfer of linezolid resistance was attempted by filter mating experiments.Results: Out of 3974 clinical isolates of enterococci received at the NRC-Enc over the period, 9 (0.2%) were LRE (MICs 8 to >32 mg/L), including 6 Enterococcus faecium and 3 Enterococcus faecalis. This overall prevalence significantly increased over the study period, reaching 0.8% in 2016. The five LRE isolated before 2016 were vanA-positive E. faecium whereas strains isolated in 2016 (one E. faecium and three E. faecalis) were susceptible to vancomycin. None of these isolates was part of an outbreak, while E. faecium strains were assigned to four different STs [17 (1), 80 (3), 412 (1) and 650 (1)] and all three E. faecalis belonged to ST480. Except for the strain isolated in 2010, all LRE were positive for optrA, which was located on plasmids (5/8) or in the chromosome (3/8). Plasmid transfer of optrA was successful in three cases.Conclusions: There has been a significant increase in the prevalence of LRE in France over time; this is due to the spread of optrA among E. faecium and E. faecalis human clinical isolates (VRE or not). [ABSTRACT FROM AUTHOR]

Objectives: Our aim was to describe the molecular epidemiology and antimicrobial resistance determinants of isolates of Neisseria gonorrhoeae with decreased susceptibility and resistance to extended-spectrum cephalosporins (ESCs) in Argentina in 2011-16.Methods: Gonococcal isolates (n=158) with decreased susceptibility and resistance to ESCs collected in 2011-16 across Argentina were subjected to WGS and antimicrobial susceptibility testing for six antimicrobials.Results: In total, 50% of the isolates were resistant to cefixime, 1.9% were resistant to ceftriaxone, 37.3% were resistant to azithromycin and 63.9% of the isolates showed an MDR phenotype. Resistance and decreased susceptibility to ESCs was mainly associated with isolates possessing the mosaic penA-34.001, in combination with an mtrR promoter A deletion, and PorB1b amino acid substitutions G120K/A121N. Phylogenetic analysis revealed two main clades of circulating strains, which were associated with the N. gonorrhoeae multiantigen sequence typing (NG-MAST) ST1407 and closely related STs, and characterized by a high prevalence rate, wide geographical distribution and temporal persistence.Conclusions: N. gonorrhoeae isolates with decreased susceptibility and resistance to ESCs in Argentina have emerged and rapidly spread mainly due to two clonal expansions after importation of one or two strains, which are associated with the international MDR NG-MAST ST1407 clone. The identification of the geographical dissemination and characteristics of these predominant clones may help to focus action plans and public health policies to control the spread of ESC resistance in Argentina. Dual antimicrobial therapy (ceftriaxone plus azithromycin) for gonorrhoea needs to be considered in Argentina. [ABSTRACT FROM AUTHOR]

Existing reducing agents for cross-linking polymers are expensive and toxic and mostly limited for water shut off applications. A gelation study was performed on a safer, cheaper, more soluble, and short-lived gel by cross-linking polyacrylamide and chromium as a cross-linking agent using a rheometer and bead-pack porous media. The effect of concentration of sodium thiosulfate as the reducing agent was investigated to determine conditions for optimum yield strength and the gelation time and behavior which has never been published before. For a fixed minimum concentration (for the gel to form) of polyacrylamide and sodium dichromate, the gel yield strength vs. sodium thiosulfate concentration showed a somewhat bell-shaped curve initially increasing, reaching a peak at 2000 ppm, and then starting to decrease. The gelation formed by sodium thiosulfate was comparatively weak and short lived as compared to the ones formed by other reducing agents. Gel started to form instantaneously, reached a peak in 2 h, began to decrease, and then stabilized at 40 cp. The mobility reduction trends were similar to the yield strength curve. The short-lived gel could be useful to improve the waterflood mobility ratio far away from the wellbore without compromising on ease of injectivity. [ABSTRACT FROM AUTHOR]

The objective of this study was to evaluate the effect of sodium hypochlorite and chlorhexidine solutions and their inactivating agents on the push-out bond strength of mineral trioxide aggregate (MTA). One hundred fifty root slices were prepared and their root canal spaces were enlarged using diamond burs. MTA was prepared and compacted to root canal spaces. The samples were randomly separated to 4 groups that would be immersed into the selected solutions (5.25% sodium hypochlorite (NaOCl), 5.25% NaOCl and sodium thiosulfate, 2% chlorhexidine (CHX), 2% CHX and a mixture of Tween 80 and 0.3% L-alfa-lecithin) and a control group (n = 30). Push-out bond strength of each specimen was tested with universal testing machine. The data was analyzed by one-way analysis of variance and Tukey tests. There were no significant differences between the push-out bond strength values of the irrigation groups and the control group. A significant difference was found between the push-out bond strength values of NaOCl-Sodium thiosulfate and CHX-L-alpha-lecithin groups. Contact with NaOCl and its neutralizing agent with MTA after 10 minutes of setting period increased the push-out bond strength of MTA. On the other hand, any contact with CHX alone or with subsequent application using L-alfa-lecithin should be avoided since that might decrease the push-out bond strength of freshly mixed MTA. [ABSTRACT FROM AUTHOR]

Objectives: To characterize the antimicrobial susceptibility, molecular epidemiology and carbapenem resistance mechanisms in Pseudomonas aeruginosa isolates recovered from respiratory tract samples from patients with ventilator-associated pneumonia enrolled in the MagicBullet clinical trial.Methods: Isolates were collected from 53 patients from 12 hospitals in Spain, Italy and Greece. Susceptibility was determined using broth microdilution and Etest. MALDI-TOF MS was used to detect carbapenemase activity and carbapenemases were identified by PCR and sequencing. Molecular epidemiology was investigated using PFGE and MLST.Results: Of the 53 isolates, 2 (3.8%) were considered pandrug resistant (PDR), 19 (35.8%) were XDR and 16 (30.2%) were MDR. Most (88.9%) of the isolates from Greece were MDR, XDR or PDR, whereas fewer of the isolates from Spain (33.3%) and Italy (43.5%) showed antibiotic resistance. Three Greek isolates were resistant to colistin. Overall, the rates of resistance of P. aeruginosa isolates to imipenem, ciprofloxacin, ceftolozane/tazobactam and ceftazidime/avibactam were 64.1%, 54.7%, 22.6% and 24.5%, respectively. All isolates resistant to ceftolozane/tazobactam and ceftazidime/avibactam (Greece, n = 10; and Italy, n = 2) carried blaVIM-2. Spanish isolates were susceptible to the new drug combinations. Forty-eight restriction patterns and 27 STs were documented. Sixty percent of isolates belonged to six STs, including the high-risk clones ST-111, ST-175 and ST-235.Conclusions: MDR/XDR isolates were highly prevalent, particularly in Greece. The most effective antibiotic against P. aeruginosa was colistin, followed by ceftolozane/tazobactam and ceftazidime/avibactam. blaVIM-2 is associated with resistance to ceftolozane/tazobactam and ceftazidime/avibactam, and related to highly resistant phenotypes. ST-111 was the most frequent and disseminated clone and the clonal diversity was lower in XDR and PDR strains. [ABSTRACT FROM AUTHOR]

A quenching agent is commonly added to chlorinated, reclaimed water during sample collection to prevent chlorine-mediated die-off of viable microbiota. However, the effect of quenching on downstream 16S rRNA-based bacterial community analyses is unclear. We conducted a side-by-side comparison of 16S rRNA sequencing data from reclaimed water samples quenched with sodium thiosulfate and non-quenched samples. Our data showed that 16 S rRNA processing and sequencing methods, and resulting bacterial profiles, were not negatively impacted by quenching. [ABSTRACT FROM AUTHOR]

Objectives: Rates of Clostridioides (Clostridium) difficile infection (CDI) are higher in North Wales than elsewhere in the UK. We used WGS to investigate if this is due to increased healthcare-associated transmission from other cases.Methods: Healthcare and community C. difficile isolates from patients across North Wales (February-July 2015) from glutamate dehydrogenase (GDH)-positive faecal samples underwent WGS. Data from patient records, hospital management systems and national antimicrobial use surveillance were used.Results: Of the 499 GDH-positive samples, 338 (68%) were sequenced and 299 distinct infections/colonizations were identified, 229/299 (77%) with toxin genes. Only 39/229 (17%) toxigenic isolates were related within ≤2 SNPs to ≥1 infections/colonizations from a previously sampled patient, i.e. demonstrated evidence of possible transmission. Independent predictors of possible transmission included healthcare exposure in the last 12 weeks (P = 0.002, with rates varying by hospital), infection with MLST types ST-1 (ribotype 027) and ST-11 (predominantly ribotype 078) compared with all other toxigenic STs (P < 0.001), and cephalosporin exposure in the potential transmission recipient (P = 0.02). Adjusting for all these factors, there was no additional effect of ward workload (P = 0.54) or failure to meet cleaning targets (P = 0.25). Use of antimicrobials is higher in North Wales compared with England and the rest of Wales.Conclusions: Levels of transmission detected by WGS were comparable to previously described rates in endemic settings; other explanations, such as variations in antimicrobial use, are required to explain the high levels of CDI. Cephalosporins are a risk factor for infection with C. difficile from another infected or colonized case. [ABSTRACT FROM AUTHOR]

Sulfur mustard (SM) is a blistering chemical warfare agent that was used during the World War I and in the Iraq–Iran conflict. The aim of this paper is to discuss and critically review the published results of experiments on the treatment of SM poisoning based on our clinical and research experience. The victims must remove from the contaminated zone immediately. The best solution for decontamination is large amounts of water, using neutral soap and 0.5% sodium hypochlorite. Severely intoxicated patients should be treated according to advanced life support protocols and intensive care therapy for respiratory disorders and the chemical burn. Sodium thiosulfate infusion (100–500 mg/kg/min) should be started up to 60 min after SM exposure. However, N-acetyle cysteine (NAC) is recommended, none of them acts as specific or effective antidote. The important protective and conservative treatment of SM-induced pulmonary injuries include humidified oxygen, bronchodilators, NAC as muculytic, rehydration, mechanical ventilation, appropriate antibiotics and respiratory physiotherapy as clinically indicated. Treatment of acute SM ocular lesions start with topical antibiotics; preferably sulfacetamide eye drop, continue with lubricants, and artificial tears. Treatment for cutaneous injuries include: moist dressing; preferably with silver sulfadiazine cream, analgesic, anti-pruritic, physically debridement, debridase, Laser debridement, followed by skin autologous split-thickness therapy as clinically indicated. The new suggested medications and therapeutic approaches include: anti-inflammatory agents, Niacinamide, Silibinin, Calmodulin antagonists, Clobetasol, full-thickness skin grafting for skin injuries; Doxycycline; Bevacizumab, and Colchicine for ocular injuries. Recommended compounds based on animal studies include Niacinamide, Aprotinin, des-aspartate-angiotensin-I, Gamma-glutamyltransferase, vitamin E, and vitamin D. In vitro studies revealed that Dimethylthiourea, L-nitroarginine, Methyl-ester, Sodium pyruvate, Butylated hydroxyanisole, ethacrynic acid, and macrolide antibiotics are effective. However, none of them, except macrolide antibiotics have been proved clinically. Avoidance of inappropriate polypharmacy is advisable. [ABSTRACT FROM AUTHOR]

Background: Calciphylaxis (CPX) is a rare and life-threatening disease characterized by vascular calcification and development of painful and necrotizing skin lesions with a challenging management. Mechanisms of CPX are complex and include an imbalance between vascular calcification promoters and inhibitors, and frequently vitamin K deficiency.Objectives: To describe the various presentations and identify predictive factors of death in patients with CPX.Methods: In this multicenter retrospective study, we included 71 CPX patients followed in South-West France (n = 26) and in French Polynesia (n = 45), and who all received sodium thiosulfate (25 g thrice weekly for a median of 61 days).Results: Characteristics at presentation significantly differed between metropolitan and Polynesian French patients. Polynesians were less frequently on regular dialysis at the onset of CPX, had a higher incidence of diabetes mellitus and obesity, more disturbances of calcium-phosphorus metabolism, and received vitamin K antagonists less frequently than patients from South-West France. Despite intensive management, the 1-year mortality rate was 66% and median time to death was 200 days (IQR, 40; 514). The number of body areas involved (i.e., three: OR 2.70 [1.09; 6.65], p = 0.031; four: OR 8.79 [1.54; 50.29], p = 0.015) was the only predictive factor for death, whereas application of topical cerium nitrate-silver sulfadiazine was protective (OR 0.44 [0.20; 0.99], p = 0.046). Surgical debridement, hyperbaric oxygenation therapy, and geographical origin were not associated with overall outcomes.Conclusions: Cerium nitrate may lead to vascular decalcification and chelation of reactive oxygen species, and prevent infection. Cerium nitrate-silver sulfadiazine was associated with better outcomes and should be tested in a prospective comparative trial in CPX patients. [ABSTRACT FROM AUTHOR]

Anode slime is an extremely valuable secondary resource for the recovery of silver and has attracted wide attentions. Effective metal recovery is usually constrained by either environmental hazards or high consumption of lixiviant for cyanide and non-cyanide leaching reagents. To tackle these issues in the process of silver recovery from anode slime, this research demonstrated a new leaching system with using an efficient oxidant which encapsulates cyanide into ferric complexes to ensure it not releasing into the environment while effective silver recovery was achieved. Comparing with the traditional tetra-amine copper oxidant, it was found that the dissolution rate of silver was significantly improved and leachate consumption was largely decreased. The effects of stirring speed, sodium thiosulfate concentration, oxidant concentration, solution pH and time on silver dissolution were investigated. When the novel system of iron-encapsulated cyanide was applied to extract silver from anode slime, the final conversion rates of silver was 97% after 60 minutes. This system has great potential in silver recovery from anode slime. [ABSTRACT FROM AUTHOR]

Objectives: To investigate the prevalence and molecular characteristics of ESBL-producing Escherichia coli (ESBL-EC) in faecal samples from dairy cows in China.Methods: In total, 651 faecal samples were collected from cows distributed among the 10 provinces of China. Potential ESBL-EC isolates were cultured on selective medium. The clonal relatedness of the ESBL-EC isolates was assessed using MLST. WGS was conducted on 3 mcr-positive isolates and 14 additional randomly selected ESBL-EC isolates. Southern blot, S1-PFGE and conjugation were performed for mcr-1-carrying isolates. The genetic environment of the pMCR-JLF4 plasmid was also analysed.Results: In total, 290 unique ESBL-EC isolates were detected from 284 cows (43.6%). Alleles of CTX-M were observed in 94.1% (273/290) of all isolates. The most prevalent genotypes observed in this study were blaCTX-M-14, blaCTX-M-15, blaCTX-M-17 and blaCTX-M-55. Differentiation of 79 STs with a polyclonal structure was accomplished using MLST. Clonal complex 10 was the most prevalent major complex detected here. Furthermore, the mcr-1 gene was detected in three isolates. The complete sequence of the mcr-1-containing pMCR-JLF4 was determined. The plasmid was 66.7 kb in length, with a genetic structure of nikA-nikB-mcr-1-pap2. Conjugation analysis confirmed that the mcr-1 gene in pMCR-JLF4 was transferable without the assistance of the ISApl1 gene.Conclusions: The data presented here suggest high prevalence of ESBL-EC in Chinese cow farms. Furthermore, it was clearly demonstrated that commensal E. coli strains can be reservoirs of blaCTX-M genes, potentially contributing to the dissemination and transfer of the mcr-1 gene to pathogenic bacteria among cows. [ABSTRACT FROM AUTHOR]

Background: Cisplatin-induced hearing loss is frequent and severe. Antioxidants such as sodium thiosulfate (STS) can neutralize the effects of cisplatin. The objective of the trial was to test the efficacy of trans-tympanic injections of a STS gel to prevent cisplatin-induced ototoxicity. Methods: Eligible participants were newly diagnosed patients with stage III or IV squamous cell carcinoma of the mouth, oropharynx, hypopharynx, or larynx and scheduled to be treated by concurrent chemoradiation (CCR). Patients with asymmetric hearing were not eligible. The planed treatment included cisplatin 100 mg/m2 at days 1, 22 and 43. A baseline pre-treatment complete audiometric evaluation (pure tone at frequencies ranging from 0.5 to 14 kHz, bone conduction at 0.5–4 kHz and DPOAEs) was performed. Adverse effects were noted according to CTCAE. On the day before the beginning of CCR, eligible and consenting patients were randomized to receive a trans-tympanic injection of the gel either in the left ear or in the right ear. A final post-treatment complete audiometric evaluation was scheduled to be performed 1 month after the end of CCR by audiologists kept blind to the ear assignment. For the main outcome, the permanent threshold shift (PTS) in decibel (dB) was calculated as the difference between the final and baseline measures at all pure tone frequencies at 0.5–14 kHz for each patient and for each ear. The main outcome was assessed blindly in a mixed linear model with the PTS as the dependent variable and intervention, frequency, their interaction and radiation dose to the cochlea as independent variables. Results: Between January 2015 and April 2016, 13 patients were randomized. The trial was stopped in June 2016 for poor accrual. The average loss of hearing over all frequencies was 1.3 dB less for treated ears compared to control ears. Although not statistically (p = 0.61) nor clinically significant, the difference was in favor of the treated ears for all frequencies between 3 and 10 kHz. Conclusions: Our trial suggests that STS deposited on the round window was safe for the middle and inner ears. More work is needed to improve the efficacy of trans-tympanic injections of cisplatin antidotes. Trial registration: ClinicalTrials.gov, NTC02281006, Registered 3 November 2014. [ABSTRACT FROM AUTHOR]

Background: Vancomycin-resistant Enterococcus faecium (VREfm) represent a major source of nosocomial infection worldwide. In Australia, there has been a recent concerning increase in bacteraemia associated with the vanA genotype, prompting investigation into the genomic epidemiology of VREfm.Methods: A population-level study of VREfm (10 November-9 December 2015) was conducted. A total of 321 VREfm isolates (from 286 patients) across Victoria State were collected and sequenced with Illumina NextSeq. SNPs were used to assess relatedness. STs and genes associated with resistance and virulence were identified. The vanA-harbouring plasmid from an isolate from each ST was assembled using long-read data. Illumina reads from remaining isolates were then mapped to these assemblies to identify their probable vanA-harbouring plasmid.Results: vanA-VREfm comprised 17.8% of isolates. ST203, ST80 and a pstS(-) clade, ST1421, predominated (30.5%, 30.5% and 37.2%, respectively). Most vanB-VREfm were ST796 (77.7%). vanA-VREfm were more closely related within hospitals versus between them [core SNPs 10 (IQR 1-357) versus 356 (179-416), respectively], suggesting discrete introductions of vanA-VREfm, with subsequent intra-hospital transmission. In contrast, vanB-VREfm had similar core SNP distributions within versus between hospitals, due to widespread dissemination of ST796. Different vanA-harbouring plasmids were found across STs. With the exception of ST78 and ST796, Tn1546 transposons also varied. Phylogenetic analysis revealed Australian strains were often interspersed with those from other countries, suggesting ongoing cross-continental transmission.Conclusions: Emerging vanA-VREfm in Australia is polyclonal, indicating repeat introductions of vanA-VREfm into hospitals and subsequent dissemination. The close relationship to global strains reinforces the need for ongoing screening and control of VREfm in Australia and abroad. [ABSTRACT FROM AUTHOR]

Objectives: To determine the molecular characteristics of ESBL-producing Escherichia coli (ESBL-E) collected during a longitudinal study on an organic broiler farm in order to investigate clonal expansion and horizontal gene transfer.Methods: Isolates were obtained from a longitudinal study performed previously on an organic broiler fattening farm. Samples from individually followed-up broilers, the broiler house, the transport van and persons that took the samples, taken at several timepoints (days 1, 3, 4, 7, 10, 42 and 70) within a production round and during the consecutive one (days 1, 2, 3 and 70), had been investigated for the occurrence of ESBL-E. In the current study, ESBL genes and MLST STs of these ESBL-E were determined. Plasmids were characterized and subtyped.Results: On arrival in round_1, ESBL-E of ST88 predominated, while on days 3, 4, 7 and 10 ST10 was most often found and at slaughter age ST155 and ST1551 prevailed. A shift in STs was also observed in round_2. None of the 35 individually selected broilers followed up in round_1 was positive for the same ESBL-E ST at all sampling times. All isolates carried CTX-M-1 group genes, confirmed as blaCTX-M-1 in 158 isolates. Further analysis of 36 isolates of different STs showed blaCTX-M-1 on IncI1/ST3 plasmids.Conclusions: The rapid dissemination of ESBL-E on this broiler farm was not due to the spread of one specific E. coli clone, but most likely the result of horizontal transfer of an IncI1/ST3 plasmid carrying blaCTX-M-1 resulting in a shift in the predominant ESBL-E population in broilers. [ABSTRACT FROM AUTHOR]

Sulfur oxidising bacteria (SOB) are of great importance in the sulfur biogeochemical cycle and removal of undesirable hydrogen sulfide in biogas production. This study evaluated the sulfide oxidising ability of bacteria from different soils using bromocresol purple dye reduction method and spectrophotometry. The study sites were the abattoir, automobile workshop, dumpsite, rhizospheric soil, and sewer disposal sites. Starkey broth was used as a selective culture broth and sodium thiosulfate as an enrichment culture medium, both at pH 8.00. Sulfur ion evaluation was carried out using spectrophotometry at 450 nm wavelength. 16S rRNA sequencing of promising SOB was investigated. The total colony count of sulfur oxidising bacteria able to reduce the bromocresol dye on the sodium thiosulfate agar ranged from 2.00 × 103 cfu/g from the abattoir, dumpsite and sewer disposal sites to 1.50 × 104 cfu/g from the automobile workshop. Paenibacillus ripae and Staphylococcus aureus had the highest sulfur oxidation absorbance of 1.72 and 1.65 with a pH of 5.75 and 5.90 respectively. The pH of the studied bacteria on the sixth day of incubation ranged from 5.69 to 6.03. Bacillus cereus , P. ripae and S. aureus demonstrated most promising potential as sulfur oxidising agents. This work revealed the presence of SOB from different locations with relatively low pH and indicates potential importance of studied bacteria in the removal of hydrogen sulfide in biogas that may not support bio-corrosion. [Display omitted] • The sulfur oxidising bacteria (SOB) are suitable for biological desulfurization. • The SOB moderately reduce pH which makes them unlikely able to corrode bioreactors. • Highest sulfur oxidising bacteria count was recorded from the automobile workshop. • Paenibacillus ripae , Staphylococcus aureus and Bacillus cereus were most prevalent. [ABSTRACT FROM AUTHOR]

• Penile gangrene is a presentation of calciphylaxis and is associated with high mortality rate. Calcium level may be normal at presentation. • Superficial biopsy of the penis should only be considered if diagnosis is equivocal. Punch biopsy is preferred over excision biopsy. • Overly aggressive surgical treatment of penile gangrene is associated to poor outcomes. Sodium thiosulfate may be effective in treating penile gangrene due to calciphylaxis. • Mechanism of sodium thiosulfate is unknown but may be related to improvement in blood flow in calcified blood vessels •Further studies are required. Penile gangrene is a rare but fatal complication of calciphylaxis in end-stage renal disease (ESRD). To date, there are no guidelines on its management, and outcomes are generally poor with high mortality rate. We present a case of a diabetic patient with ESRD presenting with dry gangrene of the glans penis due to calciphylaxis and successfully treated with intravenous sodium thiosulfate (STS) and early total parathyroidectomy. We further analysed existing literatures on cases that utilized STS in the treatment of penile calciphylaxis. [ABSTRACT FROM AUTHOR]

Aberrant production of hydrogen sulfide (H2S) has been linked to preeclampsia. We hypothesized that sodium thiosulfate (STS), a H2S donor, reduces hypertension and proteinuria, and diminishes fetal growth restriction in the Dahl salt-sensitive (S) rat, a spontaneous model of superimposed preeclampsia. In addition to a control group (n = 13), two groups received STS via drinking water at a dose of 2 g (n = 9) or 3 g per kg body weight per day (n = 8) from gestational day (GD) 10 to 20. Uterine artery resistance index was measured (GD18), urinary protein excretion rate was determined (GD19), and blood pressure and fetal outcomes were evaluated (GD20). At 2 g, STS had no effect on preeclamptic symptoms or fetal outcome. At 3 g, STS reduced maternal hypertension (121.8 ± 3.0 vs. 136.3 ± 2.9), but increased proteinuria (89 ± 15 vs. 56 ± 5 mg/24 h), and relative kidney weight (0.86 ± 0.04 vs. 0.73 ± 0.02%). Fetal/placental weight ratio was reduced (3.83 ± 0.07 vs. 4.31 ± 0.08) without affecting litter size. No differences in uterine artery flow or renal histological damage were noted across treatment groups. While these data suggest a promising antihypertensive effect that could imply prolongation of preeclamptic pregnancies, the unfavorable effects on proteinuria, kidney weight, and fetal/placental weight ratio implies that clinical implementation of STS is contra-indicated until safety for mother and child can be verified.

The article presents a case study of a nine-year-old boy with a month history of headache and nausea because of medulloblastoma. He was administered with cisplatin that induces hearing-loss because of ototoxicity. It discusses the use of (STS) to prevent the progression of hearing-loss because of its otoprotective potential by inactivating oxygen free radicals and electrophilic platinum species.

Copper in copper ores is commonly determined by a manual visual titration method. The method has large errors, poor precision and poor reliability due to the need to gauge the end of the chemical reaction by a chemical indicator. Based on these disadvantages, a high precision determination method for high Cu content in Cu ores has been developed. In this new method, the terminal point is determined by intelligent potentiometric titrator automatically and the amount of sodium thiosulfate standard solution is accurate to 0.001 mL by a high-resolution dosing device. Moreover, the amount of potassium iodide is increased to eliminate the absorption of iodine with copper iodide which was produced during titration, as the copper iodide can be dissolved by high concentrations of iodide. National standard materials such as copper concentrate, chalcopyrite and lead brass with copper content ranging from 24.2% to 59.09% are determined using this method. The relative standard deviation is lower than 0.3%(n=10). The extreme differences are 0.13%, 0.21% and 0.29%, better than manual visual titration. The proposed method improves the automation for accurate determination of ores with Cu content greater than 0.5%, especially for those with Cu content more than 10%.

Bioleaching has been demonstrated to be an effective technology for the removal of heavy metals and sludge dewaterability. Since bacteria gain nutrients by diffusion of soluble compounds, the insolubility of elemental sulfur may slow the growth of bacteria. Thus, it is very important to find an energy substance quickly become available to Acidithiobacillus thiooxidans. This paper studies the improvement of sludge dewaterability and heavy metal removal with sodium thiosulfate as the source of energy for Acidithiobacillus thiooxidans. Through orthogonal experiments with specific resistance to filtration (SRF) as the target index, four factors (FeSO4 dosage, Na2S2O3 dosage, sludge reflux ratio and sludge moisture content) were identified to be the important influencing parameters. The optimal conditions were: FeSO4 dosage, 8 g/L; Na2S2O3 dosage, 1.5 g/L; sludge reflux ratio, 30%; sludge moisture content, 97%. Results indicated that the SRF of the sludge decreased from 9.89 x 1012 to 1.03 x 1011 m/kg. The removal efficiencies of heavy metals Cu, Zn, Pb and Cr could reach 83%, 78%, 31% and 38% within 3 days, respectively. These results confirm the potential of sodium thiosulfate as an alternative energy substance in bioleaching to improve sludge dewaterability as well as removal of metals. [ABSTRACT FROM AUTHOR]

Objectives: To ascertain whether the antimicrobial susceptibility of Neisseria gonorrhoeae isolates with differing susceptibilities to penicillin is associated with genogroups (GGs) and combined mutation patterns in PBP2 (penA), the multiple transfer resistance repressor (MtrR; mtrR) and porin B (PorB; porB).Methods: The susceptibility of 146 clinical N. gonorrhoeae isolates to penicillin was determined using the agar dilution method and the interpretation criteria of CLSI. The DNA sequences of penA, mtrR and porB in isolates were compared with WT sequences and mutation patterns were determined. Isolates were typed by N. gonorrhoeae multi-antigen sequence typing (NG-MAST) and STs were grouped into specific GGs.Results: The isolates tested carried 9 mutation patterns in PBP2 and 12 mutation patterns in each of MtrR and PorB. Of the 146 isolates, 121 (82.9%) were grouped into 13 different GGs. Isolates with penicillin MICs of 0.03-0.06 mg/L were significantly associated with GG25 (P < 0.05) and PBP2/MtrR/PorB mutation pattern I/WT/WT (P < 0.01). Isolates with a penicillin MIC of 1.0 mg/L were associated (P < 0.05) with: (i) GG3655 and mutation pattern XXII/A-;G45D/G120K;A121N; (ii) GG921 and mutation pattern IX/G45D/G120D;A121N; and (iii) GG1109 and mutation pattern IX/G45D/WT. Sixty percent (9/15) of penicillin-resistant isolates (MIC ≥2 mg/L) were GG3654 (P < 0.0001) and carried mutation pattern IX/G45D/G120K;A121D or IX/G45D/G120D;A121D (P < 0.05).Conclusions: Specific mutation patterns in PBP2/MtrR/PorB were associated with specific GGs and penicillin susceptibility. This approach of typing strains and resistance patterns is ideal for predicting antimicrobial resistance and should be used in instances in which gonococcal culture is not available but DNA can be obtained from clinical specimens. [ABSTRACT FROM AUTHOR]

Objectives: To analyse VIM/IMP-type MBL-producing Enterobacteriaceae isolates identified in Poland during 2006-12.Methods: Isolates were typed by PFGE, followed by MLST. blaVIM/IMP genes were amplified and sequenced within class 1 integrons. Their plasmidic versus chromosomal location was assessed by nuclease S1 and I-CeuI plus hybridization experiments. Plasmids were characterized by transfer assays and PCR-based replicon typing.Results: One hundred and nineteen VIM/IMP-positive Enterobacteriaceae cases were reported in Poland from the first case in 2006 until 2012. The patients were in 54 hospitals and were infected or colonized by 121 organisms, including Enterobacter cloacae complex (n = 64), Klebsiella oxytoca (n = 23), Serratia marcescens (n = 20) and Klebsiella pneumoniae (n = 11). The isolates represented numerous pulsotypes and mainly original STs, and carried eight integrons with blaVIM-1-like genes (blaVIM-1/-4/-28/-37/-40; n = 101), three with blaVIM-2 variants (blaVIM-2/-20; n = 17) and one with blaIMP-19 (n = 3). Six integrons were new, and five and two formed prevalent families of In238-like (n = 96) and In1008-like (n = 16) elements, respectively. In238 (aacA4-blaVIM-4rpt) and In1008 (blaVIM-2-aacA4) had been originally observed in Polish Pseudomonas aeruginosa, suggestive of their transfer to enterobacteria, followed by spread and diversification. Four organisms have disseminated inter-regionally, i.e. Enterobacter hormaechei ST90 with plasmidic In238/In238a integrons (n = 36), K. oxytoca ST145 with a chromosomal In237-like element (n = 18) and two subclones of E. hormaechei ST89 with In1008- or In238-type variants (n = 8 and n = 7, respectively).Conclusions: The epidemiology of VIM/IMP-producing Enterobacteriaceae in Poland has revealed a remarkable number of specific or novel characteristics of the organisms, with some possible links to other mid-southern European countries. [ABSTRACT FROM AUTHOR]

Background Calcific uremic arteriolopathy (CUA), also known as calciphylaxis, is a rare but life-threatening condition predominately occurring in patients with end-stage renal disease on dialysis. In the absence of randomized clinical trials to guide management, clinicians must rely on observational data. We have previously reported the outcomes of our multi-intervention management in seven patients and now present a larger series of patients with extended follow-up. Methods We performed a retrospective analysis of all patients diagnosed with CUA at a single academic center between 2008 and 2017. We identified 24 patients including 13 hemodialysis, 8 peritoneal dialysis and 3 predialysis Stage 5 chronic kidney disease patients. Results Mean age at diagnosis was 60.5 years (range 35–83) and mean follow-up 30.5 months (range <1–99). Patients were predominately female (71%) and Caucasian (83%) with diabetes mellitus diagnosed in 16 of 24 patients. Fifteen of 24 patients had ulcerating lesions suggestive of advanced disease and 20 of 24 had extensive involvement (bilateral disease or lesion size >5 cm). Treatment consisted of intensive hemodialysis (>20 h per week), sodium thiosulfate, wound care, analgesics and discontinuation of trigger medications including warfarin. Hyperbaric oxygen, cinacalcet, bisphosphonates and vitamin K were used in some cases. Overall 1 year mortality was 41% (9/22) and overall mortality at the end of follow-up was 64% (14/24). Cause of death was felt to be attributable to CUA in only four cases (16.7%). Complete or partial resolution of lesions occurred in 17 of 24 patients. One patient had recurrence of CUA 20 months after initial diagnosis. Conclusions Although mortality remains high in this group, direct CUA-attributable mortality is lower than historic reports. We conclude that a multi-intervention approach can be successful in treating a group of patients with severe CUA lesions. [ABSTRACT FROM AUTHOR]

In order to provide a fundamental basis for treatment of wastewater from desulfurization of coke oven gas to recover pure salt, solid-liquid equilibrium data of Na 2 S 2 O 3 -Na 2 SO 4 -H 2 O system at T  = (278.15, 283.15, 291.15, 333.15 or 353.15) K were measured. The experimental data was obtained using the isothermal solution saturation method and Schreinemaker’s wet residue method. The solid-liquid phase diagrams of the ternary system were constructed. The ternary phase diagrams turned out to be simple eutectic type containing one invariant point, two univariant curves, and two single-salt crystallization regions. It was found that the crystallization region of Na 2 SO 4 is larger than that of Na 2 S 2 O 3 and expands with the increasing of temperature. But the crystallization region of Na 2 S 2 O 3 decreases with the increasing of temperature. Through analyzing the thermodynamic characteristics of Na 2 S 2 O 3 and Na 2 SO 4 , two crystallization methods for separating the mixture of Na 2 S 2 O 3 -Na 2 SO 4 were put forward. A simple comparison of the two crystallization methods was carried out. [ABSTRACT FROM AUTHOR]

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Key Clinical Message: Sodium thiosulfate (STS), first‐line treatment for calcific uremic arteriolopathy, causes a mild asymptomatic acidosis in many patients. However, severe, life‐threatening acidosis out of proportion with the expected acid load of STS may occur, potentially due to metabolism of STS to hydrogen sulfide. [ABSTRACT FROM AUTHOR]

Background: Ingestion of cyanide may not manifest immediately in acute life-threatening symptoms. This delay presents an opportunity for recognition and appropriate management. Case Report: A 23 -year-old male purchased sodium cyanide through an internet order for suicidal gesture. He mixed sodium cyanide (5 grams) with cola soft drink (350 mL) to produce hydrogen cyanide. The patient inhaled cyanide gas for 30 minutes, however, he did not lose consciousness. He then drank the entire solution, causing him to vomit. The patient presented to the emergency medicine department about two hours after ingestion. He was conscious, and his vital signs were normal. Blood chemistries revealed wide anion gap metabolic acidosis (anion gap 16 mmol/L). Arterial blood gas and venous blood gas on arrival demonstrated no acidosis but narrow arterial and venous oxygen saturation gap (3%). He was treated with 12.5 grams of sodium thiosulfate intravenously, 5 0 grams of activated charcoal administered orally, and other supportive care. The patient condition improved clinically and laboratory. The narrow arterial-venous oxygen saturation gap was resolved (52%) at four hours post treatment. Hydrogen cyanide levels in patient's plasma and urine samples were confirmed by Gas Chromatography Mass Spectrometry methods. Conclusion: The patient was a confirmed case of acute cyanide poisoning, exhibiting the early signs of cyanide poisoning, and was successfully treated with sodium thiosulfate alone. [ABSTRACT FROM AUTHOR]

Objectives: To discover the Escherichia coli STs and associated resistance mechanisms in the community in Islamabad, Pakistan by analysis of E. coli isolates in sewage.Methods: One hundred and ten E. coli were isolated from sewage across the city of Islamabad without antibiotic bias and confirmed as E. coli by MALDI-TOF MS. Isolates were characterized by fumC/fimH (CH) typing and core-genome MLST. Resistance mechanisms, virulence genes, phylotypes and plasmid incompatibility types were determined in a subset of isolates by in silico analysis. The genomic position of blaCTX-M-15 was determined using S1-PFGE, probing and Nanopore MinION sequencing.Results and conclusions: The most prevalent STs were ST394, ST10 and ST648, accounting for 39% of all isolates collected and were found at many sites across Islamabad. Carbapenemase genes were absent and only a single isolate of ST131 was found. The most prevalent resistance mechanisms were qnrS1 and blaCTX-M-15, with blaCTX-M-15 penetrating many STs and found in 31% of all collected isolates. However, the majority of the successful STs were blaCTX-M-15 negative indicating that resistance is not the main driver of prevalence. Twenty-three percent of blaCTX-M-15 genes were chromosomally encoded and large ISEcp1-mediated insertions included qnrS1 and several plasmid genes. In all chromosomally encoded isolates no plasmid copies of blaCTX-M-15 were found. The most prevalent ST (ST394) contained many enteroaggregative E. coli virulence genes and the fimH30 variant allele previously linked to the success of ST131. [ABSTRACT FROM AUTHOR]

Objectives: To evaluate the prevalence of clinical mcr-1-positive Escherichia coli and Klebsiella pneumoniae and characterize the antimicrobial resistance profiles of mcr-1-positive E. coli and mcr-1-negative E. coli in China.Methods: A total of 6264 clinical E. coli (n = 3854) and K. pneumoniae (n = 2410) were collected from hospitalized patients from 18 to 20 hospitals as part of the China Antimicrobial Resistance Surveillance Trial (CARST) between January 2007 and June 2016. PCR was used to screen for the mcr-1 gene among all isolates. Antibiotic susceptibility testing was performed using the broth microdilution method. mcr-1-positive pathogens were then characterized by MLST and minimum spanning tree analysis using the BURST algorithm for related STs.Results: We examined 39 (0.62%) clinical isolates of mcr-1-positive E. coli and K. pneumoniae over a 10 year period. Resistance to antimicrobial agents was significantly more severe in mcr-1-positive isolates than mcr-1-negative isolates, particularly piperacillin (P = 0.008), amikacin (P < 0.0001), nitrofurantoin (P < 0.004) and fosfomycin (P < 0.0001). Among mcr-1-carrying isolates, ESBL production was as high as 84.6% (33 of 39) and 92.3% (36 of 39) of them displayed an MDR phenotype. STs suggested ubiquitous dissemination of mcr-1-carrying pathogens.Conclusions: mcr-1-carrying E. coli and K. pneumoniae displayed a lower prevalence and abundant phylogenetic diversity in mainland China. mcr-1-positive E. coli showed significant differences in antimicrobial resistance profiles compared with mcr-1-negative E. coli strains, suggesting physicians may consider prescribing different antibiotics when faced with infections caused by mcr-1-positive pathogens. [ABSTRACT FROM AUTHOR]

Aim: The study evaluated the effectiveness of three intermediate endodontic irrigating solutions in eliminating the residual sodium hypochlorite (NaOCl), thus preventing the formation of the orange-brown precipitate when 2% chlorhexidine (CHX) is used as the final irrigant. Materials and Methods: A total of 40 extracted human maxillary anterior teeth were selected, disinfected, and decoronated to obtain a standardized length of 10 mm. The teeth were prepared with Protaper universal rotary files until size F4 using 2.5% NaOCl as an irrigant during instrumentation. The teeth were then randomly divided into four groups of 10 samples each based on the irrigating solutions used during final wash sequence as follows: Group A - (2.5% NaOCl and 2% CHX), Group B - (2.5% NaOCl followed by 70% Isopropyl Alcohol and 2% CHX), Group C - (2.5% NaOCl followed by 6.25% sodium metabisulfite and 2% CHX), and Group D - (2.5% NaOCl followed by 3.86% sodium Thiosulfate and 2% CHX). The roots were sectioned longitudinally and the canal surface was evaluated under dental operating microscope (×16) for the presence of orange-brown precipitate. The results were tabulated as per scoring criteria and statistically analyzed. Statistical Analysis Used: One-way ANOVA test and post hoc Tukey's test. Results: The lowest mean score was observed in Group C, followed by Group D and Group B, respectively. In comparison, there was a statistically significant (P < 0.001) difference in results between Group C and the other experimental groups. However, there was no statistically significant difference between Group B and Group D. Conclusion: Sodium metabisulfite was found to be very effective in preventing the formation of orange-brown precipitate. [ABSTRACT FROM AUTHOR]

Background: VRE are prevalent among patients in ICUs. Non-typeable vanA VRE, due to loss of one of the genes used for MLST (pstS), have increased in Australia, suggestive of a new, hospital-acquired lineage.Objectives: To understand the significance of this lineage and its transmission using WGS of strains isolated from patients in ICUs across New South Wales, Australia.Methods: A total of 240 Enterococcus faecium isolates collected between February and May 2016, and identified by conventional PCR as vanA positive, were sequenced. Isolates originated from 12 ICUs in New South Wales, grouped according to six local health districts, and represented both rectal screening swab (n = 229) and clinical (n = 11) isolates.Results: ST analysis revealed the absence of the pstS gene in 84.2% (202 of 240) of vanA isolates. Two different non-typeable STs were present based on different allelic backbone patterns. Loss of the pstS gene appeared to be the result of multiple recombination events across this region. Evidence for pstS-negative lineage spread across all six local health districts was observed suggestive of inter-hospital transmission. In addition, multiple outbreaks were detected, some of which were protracted and lasted for the duration of the study.Conclusions: These findings confirmed the evolution, emergence and dissemination of non-typeable vanA E. faecium. This study has highlighted the utility of WGS when attempting to describe accurately the hospital-based pathogen epidemiology, which in turn will continue to inform optimal infection control measures necessary to halt the spread of this important nosocomial organism. [ABSTRACT FROM AUTHOR]

Calciphylaxis is commonly associated with end-stage renal disease patients on haemodialysis. We present a rare case of calciphylaxis in a non-uremic patient. The diagnosis was made clinically and confirmed with skin biopsy showing calcification of the dermal and subcutaneous tissues in the von Kossa stain. We believe that the combination of uncontrolled diabetes mellitus, a non-functioning paraganglioma and vitamin D deficiency in a susceptible female patient was responsible for causing calciphylaxis in our patient. An index of suspicion should be maintained by clinicians for calciphylaxis even in patients without uremia. [ABSTRACT FROM AUTHOR]

Objectives: To determine the population structure and change in drug resistance of pneumococci colonizing children before and after the introduction of the 10-valent and 13-valent pneumococcal conjugate vaccines (PCV10/13) in Brazil. Methods: We used MLST to analyse 256 pneumococcal isolates obtained from children aged <6 years before (2009-10; n = 125) and after (2014; n = 131) the introduction of the PCV10 and PCV13. Antimicrobial susceptibility and capsular types were previously determined. Results: We identified 97 different STs. Ninety (35.2%) isolates were related to international clones. The most frequent lineages were serogroup 6-CC724 (where CC stands for clonal complex) and the MDR serotype 6C-CC386 in the pre- and post-PCV10/13 periods, respectively. Penicillin-non-susceptible pneumococci (PNSP) formed 24% and 38.9% of the pre- and post-PCV10/13 isolates, respectively (P = 0.01). In the pre-PCV10/13 period, serotype 14-ST156 was the predominant penicillin-non-susceptible lineage, but it was not detected in the post-PCV10/13 period. Serotype 14-ST156 and serotype 19A-ST320 complex isolates had the highest penicillin and ceftriaxone MICs in the pre- and post-PCV10/13 periods, respectively. In turn, serotype 6C-CC386 comprised almost 30% of the PNSP and over 40% of the erythromycin-resistant isolates (MIC >256 mg/L) in the post-PCV10/13 period. Conclusions: Although PNSP strains were polyclonal, most resistant isolates belonged to a single genotype from each period. Higher erythromycin resistance prevalence (42%) in the post-PCV10/13 period was mainly attributed to MDR serotype 6C-CC386. Ongoing surveillance of pneumococcal clonal composition is important to evaluate PCV use outcomes and to identify factors other than PCVs that drive pneumococcal drug resistance evolution. [ABSTRACT FROM AUTHOR]

Objectives To determine the effect of two reducing agents (sodium ascorbate and sodium thiosulfate) on the dislocation resistance of a methacrylate and an epoxy resin based root canal sealer to sodium hypochlorite (NaOCl) treated root canal dentin. Materials and methods Single rooted teeth (n = 60) were instrumented with rotary instruments with an irrigation protocol of 3% NaOCl, 17% EDTA and 3% NaOCl in a sequence. Samples were randomly divided into three groups (n = 20) based on the final treatment: group 1 (saline), group 2 (5% sodium thiosulfate), group 3 (10% sodium ascorbate). Samples were then randomly divided into two subgroups (n = 10) based on the root canal sealer: A (a methacrylate resin sealer; EndoREZ); B (an epoxy resin sealer; AH Plus). The dislocation resistance was assessed using the push out bond strength test. The data were statistically analyzed by three-way ANOVA and a pair-wise comparison was done using the Bonferroni adjustment (P = 0.05). Results There was a significant interaction between the root thirds and the final treatment protocol for EndoREZ (P < 0.001) but not AH Plus (P > 0.05). The two experimental protocols significantly improved the adhesion (bond) strength of EndoREZ compared to saline (P < 0.05) with sodium thiosulfate producing significantly higher values than sodium ascorbate (P < 0.05). Both reducing agents did not improve the adhesion strength of AH Plus significantly when compared to the control (P > 0.05). Conclusions The bond strength of the methacrylate resin sealer EndoREZ is improved by the use of sodium thiosulfate and sodium ascorbate after irrigation with NaOCl, but these reducing agents do not improve the bond strength of the epoxy resin sealer AH Plus. Root canal sealers are differentially influenced by irrigant neutralizing (reducing) agents. [ABSTRACT FROM AUTHOR]

Sodium thiosulfate (STS) has shown promising effects in amelioration of myocardial ischemia-reperfusion injury (IR) in a rat model and is clinically useful in the treatment of chronic kidney disease (CKD) associated calciphylaxis. As the prevalence of cardiac complications is higher in CKD, we tested the effectiveness of STS in a rat model of adenine-induced vascular calcification and subjected the heart to IR. We observed an increased infarct size (29%) by TTC staining, lactate dehydrogenase (54%) and creatine kinase (32%) release in the coronary perfusate and altered hemodynamics compared to a normal rat treated with STS and subjected to IR. As functional mitochondria are essential for preserving heart from the detrimental effects of IR, we found that calcification induced mitochondrial dysfunction (reduced RCR->80%, P/O ratio->30%, ΔΨ->10% and swelling- 27%), could not be restored efficiently by STS treatment. Therefore we used nicorandil (mitochondrial potassium channel opener) along with STS as a combination therapy to treat the diseased heart and found an improvement in cardioprotection against IR injury, compared to STS alone. Upon evaluating these hearts, we found that both the cardiac mitochondria namely interfibrillar and subsarcolemmal were functionally well preserved. [ABSTRACT FROM AUTHOR]

Objectives: Information on clonal lineages and genetic platforms involved in the mobilization of carbapene-mases between Pseudomonas aeruginosa strains in Portugal is scarce. Here, we outline the genetic drivers contributing to the occurrence of blaVIM-2-producing P. aeruginosa over two decades. Methods: A collection of carbapenem-resistant P. aeruginosa clinical isolates (n = 263, 1995-2014) was screened for carbapenemase production by Blue-Carba and PCR. Antimicrobial susceptibility testing was performed according to EUCAST and clonal analysis by MLST. Nine isolates representing different integrons and STs were selected for WGS, followed by bioinformatics. Results: Twenty-seven blaVIM-2-producing P. aeruginosa belonging to 10 STs were identified, with ST179 and ST111 being the most prevalent and persistent clones. blaVIM-2 was associated with seven class I integrons frequently co-harbouring aminoglycoside resistance genes. In58 was commonly identified, followed by derivatives and In100. blaVIM-2-harbouring transposons of the Tn3 and Tn402 families were linked to different plasmids or integrative conjugative elements of the clc family. Conclusions: The dissemination of blaVIM-2 carrying integrons is associated with a complex interplay between different mobile genetic elements, including the overlooked integrative conjugative elements, and successful spread ofparticular clones. [ABSTRACT FROM AUTHOR]

In this paper, the intermediate and final reaction products of catalytic oxidation of inorganic sulfides in the presence of oxygen dissolved in the kerosene fraction and 3,3′,5,5′-tetra-tert-butyl-4,4′-stilbenequinone were investigated. The thiosulfate and sulfate are major products of the oxidation of sodium sulfide under these conditions. The intermediate and final products in the catalytic oxidation of sulfide sulfur do not affect the rate of its oxidation. The yield of catalytic oxidation products depends on the nature of the sulfide and on the pH of the solution. The catalytic cycle for sulfide oxidation in the presence of 3,3′,5,5′-tetra-tert-butyl-4,4′-stilbenequinone is shown. The role of 3,3′,5,5′-tetra-tert-butyl-4,4′-stilbenequinone is to create a new and a more effective way of electron transfer from the reducing agent (sulfide) to the oxidant (oxygen). [ABSTRACT FROM AUTHOR]

Objectives: Information on clonal lineages and genetic platforms involved in the mobilization of carbapenemases between Pseudomonas aeruginosa strains in Portugal is scarce. Here, we outline the genetic drivers contributing to the occurrence of blaVIM-2-producing P. aeruginosa over two decades.Methods: A collection of carbapenem-resistant P. aeruginosa clinical isolates (n = 263, 1995-2014) was screened for carbapenemase production by Blue-Carba and PCR. Antimicrobial susceptibility testing was performed according to EUCAST and clonal analysis by MLST. Nine isolates representing different integrons and STs were selected for WGS, followed by bioinformatics.Results: Twenty-seven blaVIM-2-producing P. aeruginosa belonging to 10 STs were identified, with ST179 and ST111 being the most prevalent and persistent clones. blaVIM-2 was associated with seven class I integrons frequently co-harbouring aminoglycoside resistance genes. In58 was commonly identified, followed by derivatives and In100. blaVIM-2-harbouring transposons of the Tn3 and Tn402 families were linked to different plasmids or integrative conjugative elements of the clc family.Conclusions: The dissemination of blaVIM-2 carrying integrons is associated with a complex interplay between different mobile genetic elements, including the overlooked integrative conjugative elements, and successful spread of particular clones. [ABSTRACT FROM AUTHOR]