Neurofilaments: light, medium, and heavy (abbreviated as NF-L, NF-M, and NF-H, respectively), which belong to Type IV intermediate filament family (IF), are neuron-specific cytoskeletal components. Neurofilaments are axonal structural components and integral components of synapses, which are important for neuronal electric signal transmissions along the axons and post-translational modification. Abnormal assembly of neurofilaments is found in several human neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS), infantile spinal muscular atrophy (SMA), and hereditary sensory-motor neuropathy (HSMN). In addition, those pathological neurofilament accumulations are known in α-synuclein in Parkinson’s disease (PD), Aβ and tau in Alzheimer’s disease (AD), polyglutamine in CAG trinucleotide repeat disorders, superoxide dismutase 1 (SOD1), TAR DNA-binding protein 43 (TDP43), neuronal FUS proteins, optineurin (OPTN), ubiquilin 2 (UBQLN2), and dipeptide repeat protein (DRP) in amyotrophic lateral sclerosis (ALS). When axon damage occurs in central nervous disorders, neurofilament proteins are released and delivered into cerebrospinal fluid (CSF), which are then circulated into blood. New quantitative analyses and assay techniques are well-developed for the detection of neurofilament proteins, particularly NF-L and the phosphorylated NF-H (pNF-H) in CSF and serum. This review discusses the potential of using peripheral blood NF quantities and evaluating the severity of damage in the nervous system. Intermediate filaments could be promising biomarkers for evaluating disease progression in different nervous system disorders.

No abstract

There is an urgent and imminent need to develop new antimicrobials to fight against antibiotic-resistant bacterial and fungal strains. In this study, a checkerboard method was used to evaluate the synergistic effects of the antimicrobial peptide P-113 and its bulky non-nature amino acid substituted derivatives with vancomycin against vancomycin-resistant Enterococcus faecium, Staphylococcus aureus, and wild-type Escherichia coli. Boron-dipyrro-methene (BODIPY) labeled vancomycin was used to characterize the interactions between the peptides, vancomycin, and bacterial strains. Moreover, neutralization of antibiotic-induced releasing of lipopolysaccharide (LPS) from E. coli by the peptides was obtained. Among these peptides, Bip-P-113 demonstrated the best minimal inhibitory concentrations (MICs), antibiotics synergism, bacterial membrane permeabilization, and supernatant LPS neutralizing activities against the bacteria studied. These results could help in developing antimicrobial peptides that have synergistic activity with large size glycopeptides such as vancomycin in therapeutic applications.

Predicting unexpected intensive care unit (ICU) re-admission and mortality after critical illness is difficult. This study assessed the associations between eosinopenia on the day of ICU discharge and outcomes after critical illness. This retrospective cohort study involved a total of 1446 critically ill patients who survived their first ICU admission between January 2009 and March 2010 in a multidisciplinary ICU in Western Australia. Eosinopenia was defined as eosinophil count <0.01×10 9 /l and the date of censor for survival was 31 october 2011. of the 1446 patients included in the study, 106 patients (7.3%) were re-admitted to the ICU during the same hospitalisation and 178 patients died (12.3%) after ICU discharge. Eosinopenia at ICU discharge occurred in 130 patients (9.7%) and was more common among those who were subsequently re-admitted (18.6 vs 8.6%) or died after ICU discharge (22.5 vs 7.5%). Eosinopenia remained associated with ICU re-admission (odds ratio 2.50, 95% confidence interval 1.38-4.50; P=0.002) and post-ICU mortality (hazard ratio 2.65, 95% confidence interval 1.77-3.98; P=0.001) after adjusting for age, gender, nocturnal discharge, neutrophil count at ICU discharge, elective surgical admission, Sequential organ Failure Assessment scores, Acute Physiology and Chronic Health Evaluation II predicted mortality and chronic medical diseases. Eosinopenia at ICU discharge explained about 8.4% of the variability and was the third most important factor in explaining the variability in survival after ICU discharge. In summary, eosinopenia at ICU discharge was associated with an increased risk of unexpected ICU re-admission and post-ICU mortality.