History of the streptothricin antibiotics and evidence for the neglect of the streptothricin resistome.

The streptothricin antibiotics were among the first antibiotics to be discovered from the environment and remain some of the most recovered antimicrobials in natural product screens. Increasing rates of antibiotic resistance and recognition that streptothricin antibiotics may play a role in countering so-called super-bugs has led to the re-evaluation of their clinical potential. Here we will review the current state of knowledge of streptothricins and their resistance in bacteria, with a focus on the potential for new resistance mechanisms and determinants to emerge in the context of potential widespread clinical adoption of this antibiotic class.

The Logic and Value of the Presumption of (Failing That, an Incapacity Defence).

Children who do not understand the serious wrongness of their actions lack criminal capacity and cannot be convicted. At common law, children under seven are deemed to lack criminal capacity, children over 14 possess full capacity and children between seven and 14 are rebuttably presumed to lack capacity; the prosecution must prove capacity beyond reasonable doubt. Australia has increased the minimum age of criminal responsibility (MACR) to 10 and is considering a further increase.

Effects of a True Prophylactic Treatment on Hippocampal and Amygdala Synaptic Plasticity and Gene Expression in a Rodent Chronic Stress Model of Social Defeat.

Post-traumatic stress disorder (PTSD) is a complex stress-related disorder induced by exposure to traumatic stress that is characterized by symptoms of re-experiencing, avoidance, and hyper-arousal. While it is widely accepted that brain regions involved in emotional regulation and memory-e.g.

Functional and Structural Characterization of Diverse NfsB Chloramphenicol Reductase Enzymes from Human Pathogens.

Phylogenetically diverse bacteria can carry out chloramphenicol reduction, but only a single enzyme has been described that efficiently catalyzes this reaction, the NfsB nitroreductase from Haemophilus influenzae strain KW20. Here, we tested the hypothesis that some NfsB homologs function as housekeeping enzymes with the potential to become chloramphenicol resistance enzymes. We found that expression of H.

Mosaic Ends Tagmentation (METa) Assembly for Highly Efficient Construction of Functional Metagenomic Libraries.

Functional metagenomic libraries, physical bacterial libraries which allow the high-throughput capture and expression of microbiome genes, have been instrumental in the sequence-naive and cultivation-independent exploration of metagenomes. However, preparation of these libraries is often limited by their high DNA input requirement and their low cloning efficiency. Here, we describe a new method, mosaic ends tagmentation (METa) assembly, for highly efficient functional metagenomic library preparation.

A NIST facility for resonant soft x-ray scattering measuring nano-scale soft matter structure at NSLS-II.

We present the design and performance of a polarized resonant soft x-ray scattering (RSoXS) station for soft matter characterization built by the national institute of standards and technology at the national synchrotron light source-II (NSLS-II). The RSoXS station is located within the spectroscopy soft and tender beamline suite at NSLS-II located in Brookhaven national laboratory, New York. Numerous elements of the RSoXS station were designed for optimal performance for measurements on soft matter systems, where it is of critical importance to minimize beam damage and maximize collection efficiency of polarized x-rays.

Discovery and Characterization of a Nitroreductase Capable of Conferring Bacterial Resistance to Chloramphenicol.

Widespread antibiotic resistance has led to the reappraisal of abandoned antibiotics including chloramphenicol. However, enzyme(s) underlying one form of chloramphenicol resistance, nitroreduction, have eluded identification. Here we demonstrate that expression of the Haemophilus influenzae nitroreductase gene nfsB confers chloramphenicol resistance in Escherichia coli.

Publisher Correction: Shared strategies for β-lactam catabolism in the soil microbiome.

In the version of the article originally published, the x axis of the graph in Fig. 4d was incorrectly labeled as "Retention time (min)". It should read "Reaction time (min)".

Improved Medication Management With Introduction of a Perioperative and Prescribing Pharmacist Service.

Background: The medication lists in pre-admission clinic (PAC) questionnaires completed by patients prior to surgery are often inaccurate, potentially leading to medication errors during hospitalization. Studies have shown pharmacists are more accurate when obtaining a medication history and transcribing prescription orders, thereby reducing errors.

Objective: To evaluate the impact of a PeRiopErative and Prescribing (PREP) pharmacist on postoperative medication management.

Shared strategies for β-lactam catabolism in the soil microbiome.

The soil microbiome can produce, resist, or degrade antibiotics and even catabolize them. While resistance genes are widely distributed in the soil, there is a dearth of knowledge concerning antibiotic catabolism. Here we describe a pathway for penicillin catabolism in four isolates.

Draft Genome Sequences of Three β-Lactam-Catabolizing Soil .

Most antibiotics are derived from the soil, but their catabolism there, which is necessary to close the antibiotic carbon cycle, remains uncharacterized. We report the first draft genome sequences of soil identified for subsisting solely on β-lactams as their carbon sources. The genomes encode multiple β-lactamases, although their antibiotic catabolic pathways remain enigmatic.

Next-generation approaches to understand and combat the antibiotic resistome.

Antibiotic resistance is a natural feature of diverse microbial ecosystems. Although recent studies of the antibiotic resistome have highlighted barriers to the horizontal transfer of antibiotic resistance genes between habitats, the rapid global spread of genes that confer resistance to carbapenem, colistin and quinolone antibiotics illustrates the dire clinical and societal consequences of such events. Over time, the study of antibiotic resistance has grown from focusing on single pathogenic organisms in axenic culture to studying antibiotic resistance in pathogenic, commensal and environmental bacteria at the level of microbial communities.

Antibiotic perturbation of the preterm infant gut microbiome and resistome.

The gut microbiota plays important roles in nutrient absorption, immune system development, and pathogen colonization resistance. Perturbations early in life may be detrimental to host health in the short and the long-term. Antibiotics are among the many factors that influence the development of the microbiota.

Antibiotics and the developing infant gut microbiota and resistome.

The microbial communities colonizing the human gut are tremendously diverse and highly personal. The composition and function of the microbiota play important roles in human health and disease, and considerable research has focused on understanding the ecological forces shaping these communities. While it is clear that factors such as diet, genotype of the host, and environment influence the adult gut microbiota community composition, recent work has emphasized the importance of early-life assembly dynamics in both the immediate and long-term personalized nature of the gut microbiota.

A bioassay for the detection of benzimidazoles reveals their presence in a range of environmental samples.

Cobamides are a family of enzyme cofactors that include vitamin B12 (cobalamin) and are produced solely by prokaryotes. Structural variability in the lower axial ligand has been observed in cobamides produced by diverse organisms. Of the three classes of lower ligands, the benzimidazoles are uniquely found in cobamides, whereas the purine and phenolic bases have additional biological functions.

Regiospecific formation of cobamide isomers is directed by CobT.

Cobamides, which include vitamin B₁₂ (cobalamin), are a class of modified tetrapyrroles synthesized exclusively by prokaryotes that function as cofactors for diverse biological processes. Cobamides contain a centrally bound cobalt ion that coordinates to upper and lower axial ligands. The lower ligand is covalently linked to a phosphoribosyl moiety through an alpha-glycosidic bond formed by the CobT enzyme.

Identification of specific corrinoids reveals corrinoid modification in dechlorinating microbial communities.

Cobalamin and other corrinoids are essential cofactors for many organisms. The majority of microbes with corrinoid-dependent enzymes do not produce corrinoids de novo, and instead must acquire corrinoids produced by other organisms in their environment. However, the profile of corrinoids produced in corrinoid-dependent microbial communities, as well as the exchange and modification of corrinoids among community members have not been well studied.

Potential bloodborne pathogen exposure from occult mattress damage.

A near-miss patient incident involving body fluid seeping from a mattress led to a visual inspection of 656 hospital bed mattresses of which 177 were contaminated because of occult damage to mattress covers.

Cobamide structure depends on both lower ligand availability and CobT substrate specificity.

Cobamides are members of the vitamin B12 family of cofactors that function in a variety of metabolic processes and are synthesized only by prokaryotes. Cobamides produced by different organisms vary in the structure of the lower axial ligand. Here we explore the molecular factors that control specificity in the incorporation of lower ligand bases into cobamides.

Analysis of substrate specificity in CobT homologs reveals widespread preference for DMB, the lower axial ligand of vitamin B(12).

Cobamides such as vitamin B12 (cobalamin) are produced exclusively by prokaryotes and used by many other organisms as cofactors for diverse metabolic processes. Cobamides are cobalt-containing tetrapyrroles with upper and lower axial ligands. The structure of the lower ligand varies in cobamides produced by different bacteria.

Comparison of the Bonfils and Levitan optical stylets for tracheal intubation: a clinical study.

The Bonfils and Levitan FPS scopes are rigid fibreoptic stylets that may assist routine or difficult intubation. This study compared the effectiveness of each in patients with predicted normal airways when used by specialist anaesthetists with no prior experience using optical stylets. Twelve anaesthetists and 324 elective surgical patients participated.

Teaching corner--"lumps and bumps": a practical guide to minor surgery for the Core Surgical Trainee.

The first local anaesthetic operating list faced by a Core Surgical Trainee (CT) can appear a daunting task. Fresh from Foundation Year (FY) posts, (s)he will lack experience in basic surgical techniques. At present, there is no formal training in minor surgical skills for FY doctors, and exposure to operative surgery can be variable.

Efficacy and safety of pazopanib in patients with metastatic renal cell carcinoma.

Purpose: Inactivation of the von Hippel-Lindau gene in clear-cell renal cell carcinomas (RCC) leads to overexpression of hypoxia inducible factor, a transcription factor regulating vascular endothelial growth factor (VEGF) and platelet-derived growth factor (PDGF) gene expression. Pazopanib, an angiogenesis inhibitor targeting VEGF receptor, PDGF receptor, and c-KIT, was evaluated in patients with RCC.

Patients And Methods: This phase II study was designed as a randomized discontinuation study but was revised to an open-label study on the recommendation of the data monitoring committee (based on week 12 response rate [RR] of 38% in the first 60 patients).

Engineering the binding properties of the T cell receptor:peptide:MHC ternary complex that governs T cell activity.

The potency of a T cell is determined in large part by two interactions, binding of a cognate peptide to the MHC, and binding of the T cell receptor (TCR) to this pepMHC. Various studies have attempted to assess the relative importance of these interactions, and to correlate the corresponding binding parameters with the level of T cell activity mediated by the peptide. To further examine the properties that govern optimal T cell activity, here we engineered both the peptide:MHC interaction and the TCR:pepMHC interaction to generate improved T cell activity.