PKR deficiency alters E. coli-induced sickness behaviors but does not exacerbate neuroimmune responses or bacterial load

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Inorganic Arsenic Poisoning Following An Intentional Overdose Of Realgar-Containing Niu Huang Jie Du Pian: A Case report and Literature Review

Background: Niu Huang Jie Du Pian (NHJDP) is a widely used realgar-containing Chinese medicine remedy. Most brands are composed of eight ingredients: Niuhuang (Calculus Bovis), Xionghuang (realgar), gypsum (calcium sulphate), Dahuang (Radix et Rhizoma Rhei), Huangqin (Radix Scutellariae), Jugeng (Platycodon grandiflorum), Bingpian (borneol), and Gancao (Radix Glycyrrhizae uralensis, licorice root). Most users are not aware that Xionghuang (realgar) contains arsenic disulphide [As2S2]. Inorganic arsenic poisoning after therapeutic overdoses has been reported in Chinese literature, but no report of acute, intentional overdose of NHJDP has been published. We report a case of intentional overdose of NHJDP leading to arsenic poisoning. Case Presentation: A 33-year-old woman ingested approximately 100 tablets of NHJDP bought over the counter, along with her usual antidepressants. She presented with somnolence, agitation, epigastric pain and repeated vomiting, compatible with clinical toxicities of NHJDP reported in Chinese literature. At presentation, blood and spot urine arsenic levels were 440.9 and 7,495 nmol/L, respectively. The patient’s condition improved rapidly after admission and chelation therapy was not deemed to be necessary. Discussion: Despite the self-limiting clinical course, the high arsenic level in the patient’s blood and urine raises safety concerns regarding the use of NHJDP in the community. Inconsistencies in the sales regulation of arsenic-containing products, and a lack of product label warning regarding arsenic content, may potentiate inadvertent arsenic poisoning.  Conclusion: Clinician should be aware of the possibility of inorganic arsenic poisoning when treating patients with overdose of Chinese medicine remedies that contain Xionghuang (realgar). Proper product labelling may help reduce inadvertent arsenic poisoning

Phase 1/2 multiple ascending dose trial of the prostate-specific membrane antigen-targeted antibody drug conjugate MLN2704 in metastatic castration-resistant prostate cancer

This phase 1/2 study evaluated the dose-limiting toxicity and maximum tolerated dose of MLN2704, a humanized monoclonal antibody MLN591 targeting prostate-specific membrane antigen, linked to the maytansinoid DM1 in patients with progressive metastatic castration-resistant prostate cancer

ORMIR_XCT: A Python package for high resolution peripheral quantitative computed tomography image processing

High resolution peripheral quantitative computed tomography (HR-pQCT) is an imaging technique capable of imaging trabecular bone in-vivo. HR-pQCT has a wide range of applications, primarily focused on bone to improve our understanding of musculoskeletal diseases, assess epidemiological associations, and evaluate the effects of pharmaceutical interventions. Processing HR-pQCT images has largely been supported using the scanner manufacturer scripting language (Image Processing Language, IPL, Scanco Medical). However, by expanding image processing workflows outside of the scanner manufacturer software environment, users have the flexibility to apply more advanced mathematical techniques and leverage modern software packages to improve image processing. The ORMIR_XCT Python package was developed to reimplement some existing IPL workflows and provide an open and reproducible package allowing for the development of advanced HR-pQCT data processing workflows

Heterologous expression analyses of rice OsCAS in Arabidopsis and in yeast provide evidence for its roles in cyanide detoxification rather than in cysteine synthesis in vivo

While most dicot plants produce little ethylene in their vegetative stage, many monocots such as rice liberate a relatively large amount of ethylene with cyanide as a co-product in their seedling stage when etiolated. One of the known functions of β-cyanoalanine synthase (CAS) is to detoxify the co-product cyanide during ethylene biosynthesis in higher plants. Based on a tryptic peptide sequence obtained from a partially purified CAS activity protein preparation in etiolated rice seedlings, the full-length putative rice CAS-encoding cDNA sequence (OsCAS), which is homologous to those O-acetylserine sulphydrylase (OASS) genes, was cloned. Unlike most of the CAS genes reported from dicots, the transcription of OsCAS is promoted by auxins but suppressed by ethylene. To address the function and the subcellular localization of this gene product in planta, a binary vector construct consisting of this gene appended with a yellow fluorescent protein-encoding sequence was employed to transform Arabidopsis. Specific activities on CAS and OASS of the purified recombinant protein from transgenic Arabidopsis were 181.04 μmol H2S mg−1 protein min−1 and 0.92 μmol Cys mg−1 protein min−1, respectively, indicating that OsCAS favours CAS activity. The subcellular localization of OsCAS was found mostly in the mitochondria by immunogold electron-microscopy. Chemical cross-linking and in-gel assay on a heterodimer composed of functional and non-functional mutants in a yeast expression system on OsCAS suggested that OsCAS functions as a homodimer, similar to that of OASS. Despite the structural similarity of OsCAS with OASS, it has also been confirmed that OsCAS could not interact with serine-acetyltransferase, indicating that OsCAS mainly functions in cyanide detoxification

Personal exposure to fine particles (PM2.5) and respiratory inflammation o common residents in Hong Kong

Background: Given the lack of research on the personal exposure to fine particles (PM2.5) in Hong Kong, we examined the association between short-term personal exposure to PM2.5 and their constituents and inflammation in exhaled breath in a sample of healthy adult residents

Occurrence of Highly Conjugative IncX3 Epidemic Plasmid Carrying blaNDM in Enterobacteriaceae Isolates in Geographically Widespread Areas

The emergence of New Delhi metallo-β-lactamase (NDM) in common enterobacterial species is a major concern for healthcare. Early reports have revealed that the spread of NDM involved diverse and heterogeneous plasmids. Recently, the involvement of a rare, IncX3 subtype plasmid has been increasingly recognized. Here, we studied the prevalence of IncX plasmid subtypes in 198 carbapenem-resistant Enterobacteriaceae, originating from a territory-wide active surveillance in Hong Kong in 2016. The complete sequences and biological features of the blaNDM-carrying plasmids were investigated. A total of 62 NDM-type, 21 OXA-48 type, 14 IMP-type, 8 KPC-type, 4 IMI-type producers, and 89 non-carbapenemase-producers were tested for presence of IncX subtypes. IncX3 (n = 60) was the most common subtype, followed by IncX4 (n = 6) and IncX1 (n = 2). The prevalence of IncX3 subtype in isolates producing NDM, other carbapenemase types and non-carbapenemase producers were 75.8, 21.3, and 3.4%, respectively (P < 0.001). An IncX3 plasmid (size ∼50 kb) was confirmed to carry blaNDM in 47 isolates of different enterobacterial species. Thirteen IncX3 plasmids originating from six healthcare regions in Hong Kong were completely sequenced. The results showed that the IncX3 plasmids carrying blaNDM share a high degree of sequence identity with a previously reported plasmid, pNDM-HN380 (GenBank accession JX104760), over the backbone and genetic load regions. A blast search further revealed the occurrence of identical or nearly identical IncX3 plasmids carrying blaNDM in other part of China, Korea, Myanmar, India, Oman, Kuwait, Italy, and Canada. Two IncX3 carrying blaNDM were investigated further. Conjugation experiments demonstrated that the IncX3 plasmids could be efficiently transferred to multiple enterobacterial species at frequencies that are comparable or higher than the epidemic IncFII plasmid carrying blaCTX-M (pHK01). In addition, efficient transfer of the NDM plasmids occurred over a range of temperatures. In conclusion, this study demonstrated the important role played by IncX3 in the dissemination of NDM and the occurrence of pNDM-HN380-like plasmids in geographically widespread areas. The high mobility of IncX3 plasmid across different enterobacterial species highlights the ability of this plasmid replicon to be an important vehicle in worldwide dissemination of NDM

BING, a novel antimicrobial peptide isolated from Japanese medaka plasma, targets bacterial envelope stress response by suppressing cpxR expression

Antimicrobial peptides (AMPs) have emerged as a promising alternative to small molecule antibiotics. Although AMPs have previously been isolated in many organisms, efforts on the systematic identification of AMPs in fish have been lagging. Here, we collected peptides from the plasma of medaka (Oryzias latipes) fish. By using mass spectrometry, 6399 unique sequences were identified from the isolated peptides, among which 430 peptides were bioinformatically predicted to be potential AMPs. One of them, a thermostable 13-residue peptide named BING, shows a broad-spectrum toxicity against pathogenic bacteria including drug-resistant strains, at concentrations that presented relatively low toxicity to mammalian cell lines and medaka. Proteomic analysis indicated that BING treatment induced a deregulation of periplasmic peptidyl-prolyl isomerases in gram-negative bacteria. We observed that BING reduced the RNA level of cpxR, an upstream regulator of envelope stress responses. cpxR is known to play a crucial role in the development of antimicrobial resistance, including the regulation of genes involved in drug efflux. BING downregulated the expression of efflux pump components mexB, mexY and oprM in P. aeruginosa and significantly synergised the toxicity of antibiotics towards these bacteria. In addition, exposure to sublethal doses of BING delayed the development of antibiotic resistance. To our knowledge, BING is the first AMP shown to suppress cpxR expression in Gram-negative bacteria. This discovery highlights the cpxR pathway as a potential antimicrobial target