Initial Development of a Patient-Reported Instrument Assessing Harm, Efficacy, and Misuse of Long-Term Opioid Therapy

Guidelines on long-term opioid therapy recommend frequent reassessment of harm, efficacy, and misuse of these potentially harmful and sometimes ineffective medications. In primary care, there is a need for a brief, patient-reported instrument. This report details the initial steps in the development of such an instrument. An interdisciplinary team of clinician-scientists performed four discrete steps in this study: (1) conceptualization of the purpose and function of the instrument, (2) assembly of an item pool, (3) expert rating on which items were most important to include in the instrument, and (4) modification of expert-selected items based on a reading level check and cognitive interviews with patients. A diverse panel of 47 subject matter experts was presented with 69 items to rate on a 1–9 scale in terms of importance for inclusion in the instrument. The panel highly rated 37 items: 8 related to harm, 4 related to efficacy, and 25 related to misuse. These 37 items were then tested for patient comprehension and modified as needed. Next steps in development will include further item reduction, testing against a gold standard, and assessment of the instrument’s effect on clinical outcomes

The Formation of [TiO(H2O)n]+ Cluster Ions

Gas phase [TiO(H2O)n]+ clusters are produced by laser induced plasma reactions of titanium and water, and studied using a triple quadrupole mass spectrometer. More than 60 water molecules cluster onto TiO+; but, no [Ti(H2O)n]+ clusters are observed. The cluster size distributions of [TiO(H2O)n]+ can be fit to log-normal curves. Considered in the context of other data reported herein for cluster distributions of [NbO(H2O)n]+, it is concluded that the cluster formation and growth proceed via a coalescence mechanism between [TiO(H2O)n]+ and water molecule(s), which may lead to the formation of solvation shells. Ab initio calculations were employed to gain insight into the structures and energetics of small [TiO(H2O)n]+ clusters with n = 1–3. A charge donation from the water ligand to the TiO+ ion is found, which indicates the existence of high binding energies between water and TiO+. These experimental and theoretical results further contribute to an understanding of ion-induced nucleation in general, and hydration of TiO+, in particular

Lack of trust in maternal support is associated with negative interpretations of ambiguous maternal behavior

Attachment theory assumes that children who lack trust in maternal availability for support are more inclined to interpret maternal behavior in congruence with their expectation that mother will remain unavailable for support. To provide the first test of this assumption, early adolescents (9-13 years old) were asked to assess whether ambiguous interactions with mother should be interpreted in a positive or a negative way. In our sample (n = 322), results showed that early adolescents' lack of trust in their mother's availability for support was related to more negative interpretations of maternal behavior. The associations remained significant after controlling for depressive mood. The importance of these findings for our understanding of attachment theory, attachment stability, and clinical practice are discussed

Compressive loading of the murine tibia reveals site-specific micro-scale differences in adaptation and maturation rates of bone

Loading increases bone mass and strength in a site-specific manner; however, possible effects of loading on bone matrix composition have not been evaluated. Site-specific structural and material properties of mouse bone were analyzed on the macro- and micro/molecular scale in the presence and absence of axial loading. The response of bone to load is heterogeneous, adapting at molecular, micro-, and macro-levels. INTRODUCTION: Osteoporosis is a degenerative disease resulting in reduced bone mineral density, structure, and strength. The overall aim was to explore the hypothesis that changes in loading environment result in site-specific adaptations at molecular/micro- and macro-scale in mouse bone. METHODS: Right tibiae of adult mice were subjected to well-defined cyclic axial loading for 2 weeks; left tibiae were used as physiologically loaded controls. The bones were analyzed with μCT (structure), reference point indentation (material properties), Raman spectroscopy (chemical), and small-angle X-ray scattering (mineral crystallization and structure). RESULTS: The cranial and caudal sites of tibiae are structurally and biochemically different within control bones. In response to loading, cranial and caudal sites increase in cortical thickness with reduced mineralization (-14 and -3%, p < 0.01, respectively) and crystallinity (-1.4 and -0.3%, p < 0.05, respectively). Along the length of the loaded bones, collagen content becomes more heterogeneous on the caudal site and the mineral/collagen increases distally at both sites. CONCLUSION: Bone structure and composition are heterogeneous, finely tuned, adaptive, and site-specifically responsive at the micro-scale to maintain optimal function. Manipulation of this heterogeneity may affect bone strength, relative to specific applied loads

Use of Sperm In Vitro Capacitation and Flow Cytometry to Estimate Bull Fertility

Study Description: Frozen-thawed semen from five bulls previously identified as high (48.1% and 47.7%, bulls A and B, respectively), intermediary (45.5%, bull C) or low (43.1% and 40.7%, bulls D and E, respectively) fertility, based on pregnancy per AI, were evaluated with several laboratory measures. Measures included total motility, sperm plasma membrane integrity (viability), acrosome integrity, reactive oxygen species (ROS), mitochondrial membrane energy potential (mito-potential), zinc signatures (signatures 1 to 4), and CD9 protein populations at pre-wash, post-wash, h 0 (diluted with non-capacitation media), and at 0, 3, 6, and 24 h after dilution with capacitation media and incubation at 37 ºC. Data were analyzed using the GLIMMIX procedure of SAS for repeated measures with bull, time, and the interaction as fixed effects. Bull by time interaction was significant (P ≤ 0.01) for total motility and viability. There tended (P = 0.06) to be a bull by time interaction for zinc signatures 1 + 2 combined. There was a significant effect of bull (P ≤ 0.03) for viability, viable sperm with disrupted acrosome, zinc signatures 1, 2, and 1 + 2, viable CD9- (CD9 negative), and dead CD9+ (CD9 positive). High and intermediary field fertility bulls had greater (P ≤ 0.04) percentages of viable sperm, zinc signature 2, and zinc signature 1 + 2 compared to low fertility bulls. High and intermediary fertility bulls had decreased (P ≤ 0.05) percentage of dead CD9+ compared to low fertility bulls. There was or tended to be a positive correlation between pregnancy per AI and viability (P = 0.10; r = 0.81), zinc signature 2 (P = 0.04; r = 0.89), and zinc signature 1 + 2 (P = 0.10; r = 0.80)

Remote Infrared Imaging of the Space Shuttle During Hypersonic Flight: HYTHIRM Mission Operations and Coordination

The Hypersonic Thermodynamic Infrared Measurements (HYTHIRM) project has been responsible for obtaining spatially resolved, scientifically calibrated in-flight thermal imagery of the Space Shuttle Orbiter during reentry. Starting with STS-119 in March of 2009 and continuing through to the majority of final flights of the Space Shuttle, the HYTHIRM team has to date deployed during seven Shuttle missions with a mix of airborne and ground based imaging platforms. Each deployment of the HYTHIRM team has resulted in obtaining imagery suitable for processing and comparison with computational models and wind tunnel data at Mach numbers ranging from over 18 to under Mach 5. This paper will discuss the detailed mission planning and coordination with the NASA Johnson Space Center Mission Control Center that the HYTHIRM team undergoes to prepare for and execute each mission

Impact of Cigarette Smoking Status on Pain Intensity Among Veterans With and Without Hepatitis C

Objective: Chronic pain is a significant problem in patients living with hepatitis C virus (HCV). Tobacco smoking is an independent risk factor for high pain intensity among veterans. This study aims to examine the independent associations with smoking and HCV on pain intensity, as well as the interaction of smoking and HCV on the association with pain intensity. Design/Particpants: Cross-sectional analysis of a cohort study of veterans of Operations Enduring Freedom/Iraqi Freedom/New Dawn (OEF/OIF/OND) who had at least one visit to a Veterans Health Administration (VHA) primary care clinic between 2001 and 2014. Methods: HCV was identified using ICD-9 codes from electronic medical records (EMRs). Pain intensity, reported on a 0-10 numeric rating scale, was categorized as none/mild (0-3) and moderate/severe (4-10). Results: Among 654,841 OEF/OIF/OND veterans (median age [interquartile range] = 26 [23-36] years), 2,942 (0.4%) were diagnosed with HCV. Overall, moderate/severe pain intensity was reported in 36% of veterans, and 37% were current smokers. The adjusted odds of reporting moderate/severe pain intensity were 1.23 times higher (95% confidence interval [CI] = 1.14-1.33) for those with HCV and 1.26 times higher (95% CI = 1.25-1.28) for current smokers. In the interaction model, there was a significant Smoking Status x HCV interaction (P = 0.03). Among veterans with HCV, smoking had a significantly larger association with moderate/severe pain (adjusted odds ratio [OR] = 1.50, P \u3c 0.001) than among veterans without HCV (adjusted OR = 1.26, P \u3c 0.001). Conclusions: We found that current smoking is more strongly linked to pain intensity among veterans with HCV. Further investigations are needed to explore the impact of smoking status on pain and to promote smoking cessation and pain management in veterans with HCV

Schizotypy and Behavioural Adjustment and the Role of Neuroticism

In the present study the relationship between behavioural adjustment following cognitive conflict and schizotypy was investigated using a Stroop colour naming paradigm. Previous research has found deficits with behavioural adjustment in schizophrenia patients. Based on these findings, we hypothesized that individual differences in schizotypy, a personality trait reflecting the subclinical expression of the schizophrenia phenotype, would be associated with behavioural adjustment. Additionally, we investigated whether such a relationship would be explained by individual differences in neuroticism, a non-specific measure of negative trait emotionality known to be correlated with schizotypy. 106 healthy volunteers (mean age: 25.1, 60% females) took part. Post-conflict adjustment was measured in a computer-based version of the Stroop paradigm. Schizotypy was assessed using the Schizotypal Personality Questionnaire (SPQ) and Neuroticism using the NEO-FFI. We found a negative correlation between schizotypy and post-conflict adjustment (r = -.30, p<.01); this relationship remained significant when controlling for effects of neuroticism. Regression analysis revealed that particularly the subscale No Close Friends drove the effect. Previous findings of deficits in cognitive control in schizophrenia patients were extended to the subclinical personality expression of the schizophrenia phenotype and found to be specific to schizotypal traits over and above the effects of negative emotionality

Pharmacologic treatment with CPI-613 and PS48 decreases mitochondrial membrane potential and increases quantity of autolysosomes in porcine fibroblasts

A metabolic phenomenon known as the Warburg effect has been characterized in certain cancerous cells, embryonic stem cells, and other rapidly proliferative cell types. Previously, our attempts to induce a Warburg-like state pharmaceutically via CPI-613 and PS48 treatment did augment metabolite production and gene expression; however, this treatment demonstrated a Reverse Warburg effect phenotype observed in cancer-associated stroma. In the current study, we inquired whether the mitochondria were affected by the aforementioned pharmaceutical treatment as observed in cancerous stromal fibroblasts. While the pharmaceutical agents decreased mitochondrial membrane potential in porcine fetal fibroblasts, the number and size of mitochondria were similar, as was the overall cell size. Moreover, the fibroblasts that were treated with CPI-613 and PS48 for a week had increased numbers of large autolysosome vesicles. This coincided with increased intensity of LysoTracker staining in treated cells as observed by flow cytometry. Treated fibroblasts thus may utilize changes in metabolism and autophagy to mitigate the damage of treatment with pharmaceutical agents. These findings shed light on how these pharmaceutical agents interact and how treated cells augment metabolism to sustain viability. c2019, The Author(s).Includes bibliographical references