Manifestations of Overarousal Account For the Association Between Cognitive Anxiety Sensitivity and Suicidal Ideation

Background: Recent evidence suggests an association between cognitive anxiety sensitivity and suicidal ideation. Cognitive anxiety sensitivity has also been implicated as a precursor to various forms of overarousal. These manifestations of overarousal (i.e., agitation, insomnia, nightmares, and anger) may account for the association between cognitive anxiety sensitivity and suicidal ideation. Methods: In Study 1, undergraduate students selectively sampled for recent suicidal ideation completed all measures online. In Study 2, clinical outpatients completed all measures prior to their initial intake appointments at a psychology clinic. Results: Study 1 demonstrated that agitation and insomnia individually and jointly accounted for the association between cognitive anxiety sensitivity and suicidal ideation, controlling for general anxiety and demographic variables. Study 2 replicated and extended these findings, such that, controlling for demographics, general anxiety, and physical and social anxiety sensitivity, agitation and anger each independently and together accounted for the association between cognitive anxiety sensitivity and suicidal ideation, whereas insomnia and nightmares did not. Limitations: This study utilized a cross-sectional design and self-report measures in both samples as well as a sample of undergraduate students in Study 1. Conclusions: Together, these findings suggest that agitation and anger may explain the previously established relationship between cognitive anxiety sensitivity and suicidal ideation. Targeting cognitive anxiety sensitivity in treatment may in turn reduce these forms of overarousal and thereby suicide risk

The Effects of Protein Kinase C Beta II Peptide Modulation on Superoxide Release in Rat Polymorphonuclear Leukocytes

Phorbol 12-myristate 13-acetate (PMA; a diacylglycerol mimetic) is known to augment polymorphonuclear leukocyte (PMN) superoxide (SO) release via protein kinase C (PKC) activation. However, the role of PKC beta II (βII) mediating this response is not known. It’s known that myristic acid (myr-) conjugation facilitates intracellular delivery of the cargo sequence, and that putative PKCβII activator and inhibitor peptides work by augmenting or attenuating PKCβII translocation to cell membrane substrates (e.g. NOX-2). Therefore, we hypothesize that myr- conjugated PKCβII peptide-activator (N-myr-SVEIWD; myr-PKCβ+) would increase PMA-induced rat PMN SO release, whereas, myr-PKCβII peptide-inhibitor (N-myr-SLNPEWNET; myr-PKCβ-) would attenuate this response compared to non-drug treated controls. Rat PMNs (5x106) were incubated for 15min at 370C in the presence/absence of myr-PKCβ+/- (20 μM) or SO dismutase (SOD;10μg/mL; n=8) as positive control. PMA (100nM) induced PMN SO release was measured spectrophotometrically at 550nm via reduction of ferricytochrome c for 390 sec. PMN SO release increased absorbance to 0.39±0.04 in non-drug treated controls (n=28), and 0.49±0.05 in myr-PKCβ+(n=16). This response was significantly increased from 180 seconds to 240 seconds (p\u3c0.05). By contrast, myr-PKCβ- (0.26±0.03; n=14) significantly attenuated PMA-induced SO release compared to non-drug controls and myr-PKCβ+ (p\u3c0.05). SOD-treated samples showed \u3e90% reduction of PMA-induced SO release and was significantly different from all groups (p\u3c0.01). Cell viability ranged between 94± to 98±2% in all groups as determined by 0.2% trypan blue exclusion. Preliminary results suggest that myr-PKCβ- significantly attenuates PMA-induced SO release, whereas myr-PKCβ+ significantly augments PMA-induced SO release, albeit transiently. Additional dose response and western blot experiments are planned with myr-PKCβ+/- in PMA-induced PMN SO release assays. This research was supported by the Department of Bio-Medical Sciences and the Division of Research at PCOM and by Young Therapeutics, LLC

Protein Kinase C Beta II Peptide Inhibitor Elicits Robust Effects on Attenuating Myocardial Ischemia/Reperfusion Injury

Reperfusion injury contributes to myocardial tissue damage following a heart attack partly due to the generation of reactive oxygen species (ROS) upon cardio-angioplasty. Protein kinase C beta II (PKCβII) inhibition during reperfusion with peptide inhibitor (N-myr-SLNPEWNET; PKCβII-) decreases ROS release and leukocyte infiltration in rat hind-limb and myocardial ischemia/reperfusion (I/R) studies, respectively. However, the role of activating PKCβII during reperfusion has not been previously determined. In this study, we hypothesize that myristoylated (myr)-PKCβII- will decrease infarct size and improve post-reperfused cardiac function compared to untreated controls, whereas PKCβII peptide activator (N-myr-SVEIWD; myr-PKCβII+) will show no improvement compared to control. Myristoylation of PKCβII peptides facilitate their entry into the cell in order to affect PKCβII activity by either augmenting or attenuating its translocation to cell membrane proteins, such as NOX-2. Isolated perfused rat hearts were subjected to global I(30min)/R(50min) and infused with myr-PKCβII+ (20μM; n=9), myr-PKCβII- (20µM; n=8), or plasma (control; n=9) at reperfusion. Hearts were frozen (-20oC), sectioned and stained using 1% triphenyltetrazolium chloride to differentiate necrotic tissue. The measurement of Left ventricular (LV) cardiac function was determined using a pressure transducer and infarct size was calculated as percent dead tissue vs. total heart tissue weight. Myr-PKCβII- significantly improved LV end-diastolic pressure 37±7 mmHg compared to control (58±5; p\u3c0.01) and myr-PKCβII+ (58±4; p\u3c0.01). Myr-PKCβII- significantly reduced infarct size to 14±3% compared to control (26±5%; p\u3c0.01), while myr-PKCβII+ (25±3%) showed no difference. The data indicate that myr-PKCβII- may be a putative treatment to reduce myocardial reperfusion injury when given to heart attack patients during cardio-angioplasty. Future studies are planned to determine infarct size by Image J analysis

Precision measurements of A1N in the deep inelastic regime

We have performed precision measurements of the double-spin virtual-photon asymmetry A1A1 on the neutron in the deep inelastic scattering regime, using an open-geometry, large-acceptance spectrometer and a longitudinally and transversely polarized 3He target. Our data cover a wide kinematic range 0.277≤x≤0.5480.277≤x≤0.548 at an average Q2Q2 value of 3.078 (GeV/c)2, doubling the available high-precision neutron data in this x range. We have combined our results with world data on proton targets to make a leading-order extraction of the ratio of polarized-to-unpolarized parton distribution functions for up quarks and for down quarks in the same kinematic range. Our data are consistent with a previous observation of anA1n zero crossing near x=0.5x=0.5. We find no evidence of a transition to a positive slope in(Δd+Δd¯)/(d+d¯) up to x=0.548x=0.548

Investigating insomnia as a cross-sectional and longitudinal predictor of loneliness: Findings from six samples

Loneliness has been repeatedly associated with sleep problems; however, there is a dearth of research examining the prospective relationship between insomnia and loneliness, as well as this association controlling for other psychiatric symptoms. This study evaluated the cross-sectional and prospective relationship between insomnia and loneliness using six samples: 666 undergraduates; 2785 Army recruiters; 208 adults with a history of suicidality and/or depression; 343 adult psychiatric outpatients; 326 young adults at elevated suicide risk; and 183 undergraduates. A meta-analysis also was conducted to examine the magnitude of the relationship between insomnia and loneliness across the six studies. More severe insomnia symptoms were significantly associated with greater feelings of loneliness while accounting for some (e.g., anxiety, nightmares) but not all (i.e., depression) psychiatric covariates. Findings underscore the strength of the association between insomnia and loneliness and suggest that depression may account for this relationship. Additional studies are needed to further establish the temporal relationship between these variables, delineate the role of depression in the association between insomnia and loneliness, and test whether insomnia may confer unique risk for subsequent loneliness

Model Estimates Hurricane Wind Speed Probabilities

In the United States, intense hurricanes (category 3, 4, and 5 on the Saffir/Simpson scale) with winds greater than 50 m s−1 have caused more damage than any other natural disaster [Pielke and Pielke, 1997]. Accurate estimates of wind speed exceedance probabilities (WSEP) due to intense hurricanes are therefore of great interest to (re)insurers, emergency planners, government officials, and populations in vulnerable coastal areas. The historical record of U.S. hurricane landfall is relatively complete only from about 1900, and most model estimates of WSEP are derived from this record. During the 1899–1998 period, only two category-5 and 16 category-4 hurricanes made landfall in the United States. The historical record therefore provides only a limited sample of the most intense hurricanes

Model Estimates Hurricane Wind Speed Probabilities

In the United States, intense hurricanes (category 3, 4, and 5 on the Saffir/Simpson scale) with winds greater than 50 m s−1 have caused more damage than any other natural disaster [Pielke and Pielke, 1997]. Accurate estimates of wind speed exceedance probabilities (WSEP) due to intense hurricanes are therefore of great interest to (re)insurers, emergency planners, government officials, and populations in vulnerable coastal areas. The historical record of U.S. hurricane landfall is relatively complete only from about 1900, and most model estimates of WSEP are derived from this record. During the 1899–1998 period, only two category-5 and 16 category-4 hurricanes made landfall in the United States. The historical record therefore provides only a limited sample of the most intense hurricanes