Thromboembolic risk with IVIg: Incidence and risk factors in inflammatory neuropathy patients

Our objective was to evaluate whether IV immunoglobulin (IVIg) increases the risk of thromboembolic events in neurology outpatients with inflammatory neuropathies, as there is conflicting evidence supporting this hypothesis, mainly from non-neurologic cohorts. We investigated this question over 30 months in our cohort of patients with inflammatory neuropathies receiving regular IVIg anOur objective was to evaluate whether IV immunoglobulin (IVIg) increases the risk of thromboembolic events in neurology outpatients with inflammatory neuropathies, as there is conflicting evidence supporting this hypothesis, mainly from non-neurologic cohorts. We investigated this question over 30 months in our cohort of patients with inflammatory neuropathies receiving regular IVIg and found a greater incidence of arterial and venous thromboembolic events than population-based rates determined by hospital admissions data. Vascular risk factors were more common in the event group but there were no IVIg administration factors that contributed to the risk. This study suggests that IVIg may have a small but contributory role in determining thromboembolic risk in the inflammatory neuropathy cohort and more evidence is required before it is clear whether the current primary prevention guidelines are appropriate in this group of patients.d found a greater incidence of arterial and venous thromboembolic events than population-based rates determined by hospital admissions data. Vascular risk factors were more common in the event group but there were no IVIg administration factors that contributed to the risk. This study suggests that IVIg may have a small but contributory role in determining thromboembolic risk in the inflammatory neuropathy cohort and more evidence is required before it is clear whether the current primary prevention guidelines are appropriate in this group of patients

Platforms to differentiate exotic pathovars of plant bacteria

Many of the EPPs that pose the biggest threat to the biosecurity of Australia’s plant industries are bacterial, but difficulties in identification to the subspecific or ‘ pathovar ’ level can seriously delay incursion management and affect market access. Pathovars are defined by host specificity so bio assays remain the definitive means of identification, but these require high level physical containment and can be slow and subjective , delaying diagnosis . Some pathovar - specific serological and molecular tests are available but better diagnostic methods are often required. This project used proteomics and metabolomics, platforms that identify functional molecules potentially associated with plant - pathogen interactions, to identify biomarkers that differentiate pathovars in species of Xanthomonas . Membrane - associated proteins from a collection of bacterial isolates were compared on 2Dimensional gels. Proteins that were found to be differentially expressed between distinct pathovars may be important modulators of host specificity so they were identified and the genes that encode them located by reference to genomic sequences . DNA - based assays targeting these genes were designed and validated for their specificity to the pathovar level . We have developed two new assays that provide levels of specificity not reported elsewhere in the literature. These assays specifically target the bacteria causing the different forms of citrus canker, but without cross - reaction to the closely - related organisms causing bacterial blight on cotton and Citrus Bacterial Spot. The molecular assays will be incorporated into the National Diagnostic Protocol for citrus canker through the SPHDS process. The metabolomics component has analysed metabolite expression in selected bacterial pathovars. Results showed separation between the different pathovars based on differential levels of expression of particular metabolites. These metabolites may be important determinants of pathogenicity. Neither proteomics nor metabolomics had been implemented before in the study of phytopathogenic bacteria and whilst both proved to be technically demanding, each delivered new biomarkers that differentiate phytopathogenic bacteria to a subspecific level . This confirmed the viability of these approaches as platforms to discover novel diagnostic targets. The new methods developed will be implemented into the national incursion response capability , improving the specificity of diagnostic testing available and reducing the possibility of false positive diagnosis . The project has fostered new collaborative partnerships both nationally (NSW, Victoria, WA) and internationally (to Thailand and the USA). The next phase of this work will provide a strong start - up project to the Plant Biosecurity Cooperative Research Centre ( PBCRC ) . This project has directly enhanced the plant bacteriology capacity of NSW and Australia trough the recruitment and training of science professionals and an undergraduate student , and supported the specialist training of a Thai scientist through allied project CRC20093

Nitrous oxide-induced myeloneuropathy: a case series.

BACKGROUND: Nitrous oxide (N2O) is the second most common recreational drug used by 16- to 24-year-olds in the UK. Neurological symptoms can occur in some people that use N2O recreationally, but most information comes from small case series. METHODS: We describe 119 patients with N2O-myeloneuropathy seen at NHS teaching hospitals in three of the UK's largest cities: London, Birmingham and Manchester. This work summarises the clinical and investigative findings in the largest case series to date. RESULTS: Paraesthesia was the presenting complaint in 85% of cases, with the lower limbs more commonly affected than the upper limbs. Gait ataxia was common, and bladder and bowel disturbance were frequent additional symptoms. The mid-cervical region of the spinal cord (C3-C5) was most often affected on MRI T2-weighted imaging. The number of N2O canisters consumed per week correlated with methylmalonic acid levels in the blood as a measure of functional B12 deficiency (rho (ρ)=0.44, p=0.04). CONCLUSIONS: Preventable neurological harm from N2O abuse is increasingly seen worldwide. Ease of access to canisters and larger cylinders of N2O has led to an apparent rise in cases of N2O-myeloneuropathy in several areas of the UK. Our results highlight the range of clinical manifestations in a large group of patients to improve awareness of risk, aid early recognition, and promote timely treatment

2‐Methyltetrahydrofuran (2‐MeTHF) as a versatile green solvent for the synthesis of amphiphilic copolymers via ROP, FRP, and RAFT tandem polymerizations

2‐methyltetrahydrofuran (2‐MeTHF) is a readily available, inexpensive, neoteric, bio‐based solvent. It has been adopted across a wide range of chemical processes including the batch manufacture of fine chemicals, enzymatic polycondensations and ring opening polymerizations. To reduce the environmental burden related to the synthesis of pharmaceutical‐grade polymers based on lactide and caprolactone, we envisaged the use of 2‐MeTHF. For the first time, we combined a series of metal‐free and enzymatic ROPs with free radical and controlled RAFT polymerizations (carried out separately and in tandem) in 2‐MeTHF, in order to easily tune the chemistry and the architecture of the final polymers. After a simple purification, the amphiphilic polymers were formulated into nanoparticles and tested for their cytocompatibility in three model cell lines, to assess their application as potential polymeric excipients for nanomedicines

Effects of peripheral nerve injury on parvalbumin expression in adult rat dorsal root ganglion neurons

Background: Parvalbumin (PV) is a calcium binding protein that identifies a subpopulation of proprioceptive dorsal root ganglion (DRG) neurons. Calcitonin gene-related peptide (CGRP) is also expressed in a high proportion of muscle afferents but its relationship to PV is unclear. Little is known of the phenotypic responses of muscle afferents to nerve injury. Sciatic nerve axotomy or L5 spinal nerve ligation and section (SNL) lesions were used to explore these issues in adult rats using immunocytochemistry. Results: In naive animals, the mean PV expression was 25 % of L4 or L5 dorsal root ganglion (DRG) neurons, and this was unchanged 2 weeks after sciatic nerve axotomy. Colocalization studies with the injury marker activating transcription factor 3 (ATF3) showed that approximately 24 % of PV neurons expressed ATF3 after sciatic nerve axotomy suggesting that PV may show a phenotypic switch from injured to uninjured neurons. This possibility was further assessed using the spinal nerve ligation (SNL) injury model where injured and uninjured neurons are located in different DRGs. Two weeks after L5 SNL there was no change in total PV staining and essentially all L5 PV neurons expressed ATF3. Additionally, there was no increase in PV-ir in the adjacent uninjured L4 DRG cells. Co-labelling of DRG neurons revealed that less than 2 % of PV neurons normally expressed CGRP and no colocalization was seen after injury. Conclusion: These experiments clearly show that axotomy does not produce down regulation of PV protein in the DRG. Moreover, this lack of change is not due to a phenotypic switch in PV immunoreactive (ir) neurons, or de novo expression of PV-ir in uninjured neurons after nerve injury. These results further illustrate differences that occur when muscle afferents are injured as compared to cutaneous afferents

Phylogeography of Aphanius fasciatus (Osteichthyes: Aphaniidae) in the Mediterranean Sea, with a focus on its conservation in Cyprus

Aphanius fasciatus is a small fish occurring in Mediterranean brackish environments. In Cyprus it is known from three localities separated by long stretches of coast. The genetic diversity of these populations was evaluated using fragments of two mitochondrial genes. A comparison with the other available data showed that Cyprus populations represent a distinct lineage. The other lineages are concentrated in a relatively small area between the Strait of Sicily and the Western Ionian Sea, while all other areas include a subset of these lineages, suggesting that the aforementioned area might have acted as a glacial refugium. Landlocked North-African populations diverge from all other populations, suggesting that they might have originated in the Late Pleistocene, during transgression events of the Mediterranean Sea in North-African inland water bodies. The genetic diversity of A. fasciatus varied across different Cyprus populations, with a pattern mirroring the degree of environmental degradation, which likely affected population genetic variability through demographic reductions. The three Cyprus populations showed genetic uniqueness, suggesting the need of population-based management practices; the low genetic diversity of two populations, and the number of threats affecting them, suggest that the species should be considered endangered at national level and deserves protection measures

Self-Amplifying Replicon RNA Vaccine Delivery to Dendritic Cells by Synthetic Nanoparticles.

Dendritic cells (DC) play essential roles determining efficacy of vaccine delivery with respect to immune defence development and regulation. This renders DCs important targets for vaccine delivery, particularly RNA vaccines. While delivery of interfering RNA oligonucleotides to the appropriate intracellular sites for RNA-interference has proven successful, the methodologies are identical for RNA vaccines, which require delivery to RNA translation sites. Delivery of mRNA has benefitted from application of cationic entities; these offer value following endocytosis of RNA, when cationic or amphipathic properties can promote endocytic vesicle membrane perturbation to facilitate cytosolic translocation. The present review presents how such advances are being applied to the delivery of a new form of RNA vaccine, replicons (RepRNA) carrying inserted foreign genes of interest encoding vaccine antigens. Approaches have been developed for delivery to DCs, leading to the translation of the RepRNA and encoded vaccine antigens both in vitro and in vivo. Potential mechanisms favouring efficient delivery leading to translation are discussed with respect to the DC endocytic machinery, showing the importance of cytosolic translocation from acidifying endocytic structures. The review relates the DC endocytic pathways to immune response induction, and the potential advantages for these self-replicating RNA vaccines in the near future