Evaluation in monkey of two candidate PET radioligands, [11C]RX‐1 and [18F]RX‐2, for imaging brain 5‐HT4 receptors

The serotonin subtype‐4 (5‐HT₄) receptor, which is known to be involved physiologically in learning and memory, and pathologically in Alzheimer's disease, anxiety, and other neuropsychiatric disorders—has few radioligands readily available for imaging in vivo. We have previously reported two novel 5‐HT₄ receptor radioligands, namely [methoxy‐¹¹C](1‐butylpiperidin‐4‐yl)methyl 4‐amino‐3‐methoxybenzoate; [¹¹C]RX‐1), and the [¹⁸F]3‐fluoromethoxy analog ([¹⁸F]RX‐2), and in this study we evaluated them by PET in rhesus monkey. Brain scans were performed at baseline, receptor preblock or displacement conditions using SB 207710, a 5‐HT₄ receptor antagonist, on the same day for [¹¹C]RX‐1 and on different days for [¹⁸F]RX‐2. Specific‐to‐nondisplaceable ratio (BP_ND) was measured with the simplified reference tissue model from all baseline scans. To determine specific binding, total distribution volume (V_T) was also measured in some monkeys by radiometabolite‐corrected arterial input function after ex vivo inhibition of esterases from baseline and blocked scans. Both radioligands showed moderate to high peak brain uptake of radioactivity (2–6 SUV). Regional BP_ND values were in the rank order of known 5‐HT₄ receptor distribution with a trend for higher BP_ND values from [¹⁸F]RX‐2. One‐tissue compartmental model provided good fits with well identified V_T values for both radioligands. In the highest 5‐HT₄ receptor density region, striatum, 50–60% of total binding was specific. The V_T in receptor‐poor cerebellum reached stable values by about 60 min for both radioligands indicating little influence of radiometabolites on brain signal. In conclusion, both [¹¹C]RX‐1 and [¹⁸F]RX‐2 showed positive attributes for PET imaging of brain 5‐HT₄ receptors, validating the radioligand design strategy. Synapse 68:613–623, 2014 . © 2014 Wiley Periodicals, Inc.     

Analysis of Research and Scholarship Criteria Within Promotion and Tenure Documents of US Pharmacy Schools

Objective. To describe criteria for evaluating faculty scholarship within the promotion and tenure guidance documents of US schools and colleges of pharmacy.Methods. Promotion and tenure documents were obtained from the websites of US pharmacy schools or requested via electronic mail, and institutional characteristics were collected from publicly available online data. A qualitative content analysis was conducted to systematically catalogue document characteristics and criteria for promotion and tenure.Results. Promotion and tenure guidance documents from 121 (85%) of 142 pharmacy schools were analyzed. Institutions were 55% public and equally distributed across Carnegie institutional classifications as well as geographic and extramural funding stratifications. Publications (94%) and grants and contracts (87%) were the most frequently included criteria for faculty advancement. More than 50% of schools recognized the criteria within promotion and tenure guidance documents but did not explicitly require faculty to achieve them before receiving promotion and/or tenure. For institutions that required publications for advancement, the most frequently required criterion was publication in peer-reviewed journals (47%). Few schools (22%) documented a specific number of required publications.Conclusion. This analysis provides a comprehensive review of scholarship criteria in academic pharmacy promotion and tenure guidance documents. There was wide variability among scholarship criteria, and documents often lacked specific language defining scholarship requirements. As a result, faculty may find the documents less helpful for self-assessment and preparation toward promotion and/or tenure. These benchmark data can assist pharmacy faculty and administrators in developing and revising promotion and tenure guidance documents to include clear criteria and better align with peer institutions.     

The role of race/ethnicity in cerclage efficacy

Objective: To measure the impact of race/ethnicity on cerclage efficacy, as measured by the prevalence of spontaneous preterm birth (PTB), in a cohort of patients with history-indicated, ultrasound-indicated and physical-exam indicated cerclages.

Methods: We conducted a retrospective cohort study of patients undergoing history-indicated, ultrasound-indicated and physical-exam indicated cerclage placement from January 2003 to July 2013 at a tertiary care hospital. Patients’ race/ethnicity was self-declared. Our primary outcome was spontaneous preterm birth (SPTB) Results: One hundred and eighty-one subjects met inclusion criteria. Forty-seven percent self-identified as non-Hispanic black (NHB), 12% as Hispanic and 41% as non-Hispanic white (NHW). There was no significant difference in the prevalence of SPTB p?=?0.22), nor for SPTB less than 34 or 28 weeks. Finally, there was no difference in SPTB prevalence by race after controlling for smoking, history of CKC/LEEP, and 17-OHPC with logistic regression.

Conclusion: Race/ethnicity does not appear to be associated with cerclage efficacy, as measured by the risk of SPTB, in a cohort of patients with history-indicated, ultrasound-indicated and physical-exam indicated cerclages.     

Sex Differences in Interpersonal Violence in Malawi: Analysis of a Hospital-Based Trauma Registry

Background

Although interpersonal violence (“assault”) exists in every society, the World Health Organization (WHO) estimated that 90 % of the exposure burden occurs in low- and middle-income countries. The objectives of this study were to define the incidence of assault-related injuries among subjects presenting for emergency room care secondary to sustained trauma in Lilongwe, Malawi; to measure the impact of sex on incidence, injury type, and care received; and to measure the effect of both sex and geographic location of the injury on time to presentation for medical care.

Methods

This is a retrospective cohort analysis of data prospectively collected in the Kamuzu Central Hospital Trauma Surveillance Registry from July 2008 to December 2010 (n = 23,625). We used univariate, bivariate, and logistic regression analyses to measure association of sex with variables of interest, and geospatial mapping to evaluate the association of location of assault on time to presentation for care.

Results

The mean age of our trauma cohort was 27.7 years. Assaults accounted for 26.8 % of all injuries. Of those assaulted, 21.0 % (1299) were female, who were younger (26.2 vs. 28.1 years, p < 0.001), more likely to arrive to the hospital by minibus (p < 0.001), and less likely to arrive by police (p < 0.001). Altogether 62 % of the females were assaulted in their homes—much more often than their male counterparts (p < 0.001). Females were more likely to sustain contusions (p < 0.001) and males more likely to have lacerations and penetrating stab wounds (p < 0.001) or head injury (p < 0.001). Females had delayed hospital presentation following assault (p = 0.001) and were more likely to be treated as outpatients after adjusting for age, injury type, and injury location (adjusted odds ratio 1.74, 95 % CI 1.3–2.3, p < 0.001). Assaults clustered geographically in the Lilongwe district. Delayed presentation of females occurred irrespective of proximity to the hospital.

Conclusions

This study brings attention to sex differences in assault victims. A prevention strategy focusing on sex roles and domestic abuse of women is paramount. Efforts are needed to stop dischargin female assault victims back into a potentially unsafe, abusive environment.     

Self-report and Cognitive Processing Measures of Depressive Thinking Predict Subsequent Major Depressive Disorder

We examined the utility of two measures of cognitive bias—a self-report questionnaire, the Dysfunctional Attitudes Scale (Weissman and Beck 1978), and a cognitive processing task, the Scrambled Sentences Test (Wenzlaff 1988, 1993), in predicting episodes of depression prospectively in a community-based sample of nondepressed women. When examined separately, each measure contributed significantly to predicting a subsequent diagnosis of MDD, supporting the utility of both types of measures as indicators of depression vulnerability. When examined together, each measure made an independent contribution to the prediction of MDD, raising the possibility that questionnaire and processing tasks may assess separate aspects of cognitive vulnerability to depression.     

Delivery of adipose‐derived stem cells in poloxamer hydrogel improves peripheral nerve regeneration

Introduction: Peripheral nerve damage is associated with high long‐term morbidity. Because of beneficial secretome, immunomodulatory effects, and ease of clinical translation, transplantation with adipose‐derived stem cells (ASC) represents a promising therapeutic modality. Methods: Effect of ASC delivery in poloxamer hydrogel was assessed in a rat sciatic nerve model of critical‐sized (1.5 cm) peripheral nerve injury. Nerve/muscle unit regeneration was assessed via immunostaining explanted nerve, quantitative polymerase chain reaction (qPCR), and histological analysis of reinnervating gastrocnemius muscle. Results: On the basis of viability data, 10% poloxamer hydrogel was selected for in vivo study. Six weeks after transection and repair, the group treated with poloxamer delivered ASCs demonstrated longest axonal regrowth. The qPCR results indicated that the inclusion of ASCs appeared to result in expression of factors that aid in reinnervating muscle tissue. Discussion: Delivery of ASCs in poloxamer addresses multiple facets of the complexity of nerve/muscle unit regeneration, representing a promising avenue for further study. Muscle Nerve 58 : 251–260, 2018