Operational Study to Evaluate Music-Based Neurotraining at Improving Sleep Quality,Mood, and Daytime Function in a First Responder Population

The objective of this study was to determine if a music-based intervention could be successfully used by a group of law enforcement officers and firefighters to improve measures of sleep quality, mood, and daytime function. The Wellness Program Study included 41 male and female first responders who volunteered to participate in the 8-week study investigating the use of a music-based neurofeedback therapy known as Brain Music (BM). Creating the individualized BM recordings required 5 min of brain wave activity from 4 sensors located at F3, F4, C3 and C4 sites. The music consisted of two MP3 files, one for activating and the other for relaxing, where the ratios of peak frequencies in the delta (1–4 Hz) through beta (up to 30 Hz) EEG bands were used to select the notes used and their characteristics (e.g., duration, pitch, amplitude, and symmetry) as a means to individualize the compositions for each subject. Results of the study indicated statistically significant improvements in 4 behavioral measures: sleep quality (94%), insomnia (89%), mood (74%), and daytime function (82%). These results extend earlier insomnia research of music therapy applications from the clinic into an operational setting and lay the groundwork to address many questions concerning neurofeedback interventions targeting stress management and improved job performance. The implication of this study goes beyond the utility of BM in the first responder setting to a broader audience because many persons suffer from sleep problems that negatively impact daytime function and work performance.     

The involvement of Notch signaling in melanoma vasculogenic mimicry

Notch signaling plays an important role in tumor angiogenesis. Recent studies suggest that Notch signaling also regulates the progression of primary melanomas toward an aggressive phenotype. The aim of this study was to investigate the involvement of Notch signaling pathway in organization of tumor cells into capillary-like structures (CLS), the phenomenon also known as vasculogenic mimicry (VM). Here, we show that Notch signaling cascade was constitutively active in melanoma cell lines we used. Blocking Notch signaling with the γ-secretase inhibitors, DAPT, dibenzazepine or Jagged1 neutralizing antibody resulted in stabilization of CLS indicating that Notch signaling pathway attenuates melanoma VM. We further studied this phenomenon on melanomas grafted in nude mice. Compared to control, VM channels in DAPT-treated grafted melanoma became larger and more branched. DAPT-treated melanomas also exhibited an up-regulation of MMP-2 and VEGFR1, both known as VM mediators. Moreover, we did not observe necrosis in VM channels areas of DAPT-treated melanomas. These findings indicate that VM regulated by Notch signaling may present a novel target in melanoma therapy.     

Analysis of the parameters of oxidative stress in patients with Parkinson’s disease

The increasing data provides enough evidences confirming the involvement of free radicals and other reactive oxygen species (ROS) superoxide radical ( ^. O ₂ ^? ), nitric oxide (NO ^. ), hydrogen peroxide (H₂O₂) and hydroxyl radicals ( ^. OH) in a number of physiological and pathological processes. Imbalance between levels of ROS resulting in the body and the capacity of antioxidant defense mechanisms occur oxidative stress (OS). OS is related to a number of structural and functional damages to cells and is involved in the pathogenesis of many diseases, including neurodegenerative diseases such as Alzheimer’s disease, Parkinson’s disease (PD), amyotrophic lateral sclerosis, and Huntington disease. Defects in oxidative phosphorylation and oxidative damage play an important role in neurodegenerative diseases. The aim of this study was to investigate some biomarkers of OS such as the level of lipid peroxidation measured as malondialdehyde (MDA) reactive products and activity of antioxidant enzymes superoxide dismutase (SOD) and catalase (CAT) in the blood of PD patients compared with control group of healthy volunteers. By the present research we report higher levels of MDA products and an imbalance in SOD and CAT enzyme activities in PD patients compared to the control group.     

Domestic dogs (Canis familiaris) as reservoir hosts for Rickettsia conorii

Rickettsia conorii is the causative agent of Mediterranean spotted fever (MSF) and Israeli spotted fever (ISF) transmitted by the brown dog tick Rhipicephalus sanguineus. In areas where MSF or ISF are prevalent, dogs have high prevalence of R. conorii -neutralizing antibodies. However, the true role of dogs in the persistence of the R. conorii transmission cycle is unknown, and their reservoir competence for this pathogen has remained untested. We assessed the ability of dogs infected with R. conorii to transmit the pathogen to previously uninfected Rh. sanguineus ticks. Dogs were infected either via needle-inoculation of cultured rickettsiae or naturally via infected tick bite. Dogs were monitored for clinical signs of infection, for rickettsemia by PCR, and for seroconversion and were subjected to infestation with uninfected ticks at different time points. Rh. sanguineus larvae and nymphs successfully acquired the agent from both needle-inoculated and tick-infected dogs and transmitted it transtadially. Tick-infected dogs remained infectious to ticks for at least a month postinfection. The molted ticks were, in turn, infectious to na?ve dogs. These results demonstrate that dogs are capable of acquiring R. conorii from infected Rh. sanguineus ticks and transmitting infection to cohorts of uninfected ticks, thus confirming for the first time that dogs are indeed competent reservoirs for R. conorii. In addition, dogs with different genetic backgrounds appear to differ in their susceptibility to R. conorii infection.     

Mapping and molecular characterization of novel monoclonal antibodies to conformational epitopes on NH2 and COOH termini of mammalian tryptophanyl-tRNA synthetase reveal link of the epitopes to aggregation and Alzheimer's disease

Tryptophanyl-tRNA synthetase (TrpRS) is an interferon-induced phosphoprotein with autoantigenic and cytokine activities detected in addition to its canonical function in tRNA aminoacylation. The availability of monoclonal antibodies (mAbs) specific for TrpRS is important for development of tools for TrpRS monitoring. A molecular characterization of two mAbs raised in mice, using purified, enzymatically active bovine TrpRS as the inoculating antigen, is presented in this report. These IgG1 antibodies are specific for bovine, human and rabbit but not E. coli TrpRS. Immunoreactivity and specificity of mAbs were verified with purified recombinant hTrpRS expressed in E. coli and TrpRS-derived synthetic peptides. One of the mAbs, 9D7 is able to disaggregate fibrils formed by Ser32-Tyr50 TrpRS-peptide. Epitope mapping revealed that disaggregation ability correlates with binding of 9D7 to this peptide in ELISA and immunocytochemistry. This epitope covers a significant part of N-terminal extension that suggested to be proteolytically deleted in vivo from the full-length TrpRS whereas remaining COOH-fragment possesses a cytokine activity. For epitope mapping of mAb 6C10, the affinity selected phage-displayed peptides were used as a database for prediction of conformational discontinuous epitopes within hTrpRS crystal structure. Using computer algorithm, this epitope is attributed to COOH-terminal residues Asp409-Met425. In immunoblotting, the 6C10 mAb reacts preferably with (i) oligomer than monomer, and (ii) bound than free TrpRS forms. The hTrpRS expression was shown to correlate with growth rates of neuroblastoma and pancreatic cancer cells. Immunohistochemically both mAbs revealed extracellular plaque-like aggregates in hippocampus of Alzheimer's disease brain.