Insomnia and Exacerbation of Anxiety Associated with High-EPA Fish Oil Supplements after Successful Treatment of Depression

A 54-year-old male consulted his general practitioner for increasing general anxiety and mild panic attacks despite effective treatment for recurrent major depressive disorder, which included a fish oil supplement enriched in eicosapentaenoic acid (EPA). The patient would awaken suddenly at night with shortness of breath and overwhelming worry. During the daytime, he felt a general, nonspecific anxiety and frequently experienced sympathetic activation upon confronting routine challenges. He also experienced dyspnea-induced feelings of panic. He reported that he stopped taking the fish oil supplements after several more months of symptoms, and his anxiety and insomnia then largely disappeared. Several weeks later, he resumed consumption of high-EPA fish oil at the prior dosage for 2 days. On both nights, the patient reported nighttime awakening similar to the previous episodes, followed by daytime agitation. Since halting the fish oil supplements, the anxiety and insomnia have not returned and his depression remains in remission

Ionic basis of a mechanotransduction current in adult rat dorsal root ganglion neurons

Sensory mechanical transduction – necessary for hearing, proprioception, and the senses of touch and pain – remains poorly understood. In somatosensation, even the basic properties of the mechanically sensitive excitatory ionic currents that are assumed to mediate mechanical transduction are largely undescribed. We have recorded, from the soma of rat dorsal root ganglion (DRG) neurons in vitro, whole-cell ionic currents induced by the impact of a piezo-electrically driven glass probe. This transient mechanically activated current was observed in virtually all DRG neurons tested. In ion substitution experiments the current could be carried nonselectively by most cations, including divalent and organic cations, but not by chloride or sulfate ions. In addition, the mechanically activated current carried by monovalent cations was consistently blocked by millimolar concentrations of external calcium or magnesium. Based on these results, the transient mechanical transduction current observed in somatosensory neurons in vitro is mediated by large-pore mechanically gated channels nonselective for cations but impermeable to anions

Survey of California Pharmacists\u27 Awareness of and Readiness for the New Authorities Granted by SB 493: A Pilot Study

The recent passing of Senate Bill (SB) 493 – effective on January 1, 2014 – addresses a primary care provider shortage in California by declaring pharmacists as health care providers and authorizing new roles for them in patient care. The aims of this pilot study were to examine California registered pharmacists’ awareness and knowledge of the expanded authorities granted by SB 493 as well as to assess their perception of their own readiness to exercise these new authorities. A cross-sectional, observational study was designed, and a 40-question survey was administered electronically through Qualtrics to adjunct faculty, clinical faculty, and alumni of Touro University California College of Pharmacy. All participants were aware of this new legislation. Through their responses to Likert-scale questions, pharmacists’ self-perceived readiness for each new authority was discovered. A Kruskal-Wallis test revealed no statistically significant difference among the three subgroups’ self-perceived readiness to exercise most of the new authorities, except initiating and administering vaccinations independently to those older than three years old without a physician’s collaborative practice protocol (p = 0.0123). The lower degree of self-perceived readiness to provide immunizations independently reported by adjunct faculty might have been due to not being certified as immunizers, reflecting the need to be educated on administration of vaccinations

Environmental Adaptation: Genomic Analysis of the Piezotolerant and Psychrotolerant Deep-Sea Iron Reducing Bacterium Shewanella piezotolerans WP3

Shewanella species are widespread in various environments. Here, the genome sequence of Shewanella piezotolerans WP3, a piezotolerant and psychrotolerant iron reducing bacterium from deep-sea sediment was determined with related functional analysis to study its environmental adaptation mechanisms. The genome of WP3 consists of 5,396,476 base pairs (bp) with 4,944 open reading frames (ORFs). It possesses numerous genes or gene clusters which help it to cope with extreme living conditions such as genes for two sets of flagellum systems, structural RNA modification, eicosapentaenoic acid (EPA) biosynthesis and osmolyte transport and synthesis. And WP3 contains 55 open reading frames encoding putative c-type cytochromes which are substantial to its wide environmental adaptation ability. The mtr-omc gene cluster involved in the insoluble metal reduction in the Shewanella genus was identified and compared. The two sets of flagellum systems were found to be differentially regulated under low temperature and high pressure; the lateral flagellum system was found essential for its motility and living at low temperature

Relationship among fibre type, myosin ATPase activity and contractile properties

At least two types of skeletal muscle myosin have been described which differ in ATPase activity and stability in alkaline or acidic media. Differences in ATPase characteristics distinguish Type I and Type II fibres histochemically. In this study, ATPase activity of myosin from muscles of several species with known histochemical and contractile properties has been determined to test the hypothesis that (1) myosin ATPase activity, (2) histochemical determination of fibre types and (3) maximum shortening velocity, all provide equivalent estimates of contractile properties in muscles of mixed fibre types. Maximum shortening velocity appears to be proportional to ATPase activity as expected from previous reports by Barany. However, both myosin ATPase and the maximum shortening velocity exhibit curvilinear relationships to the fraction of cross-sectional area occupied by Type II fibres. Therefore, we reject the hypothesis and conclude that histochemically determined myofibrillar ATPase does not accurately reflect the intrinsic ATPase activity or shortening velocity in muscles of mixed fibre types. Our data are consistent with the presence of more than two myosin isozymes or with a mixture of isozymes within single muscle fibres.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/42851/1/10735_2005_Article_BF01005238.pd

31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two

Background The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd. Methods We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background. Results First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001). Conclusions In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival