Search

Pharmacological targeting of the dopamine D 4 receptor (D 4 R)─expressed in brain regions that control cognition, attention, and decision-making─could be useful for several neuropsychiatric disorders including substance use disorders (SUDs). This study focused on the synthesis and evaluation of a novel series of benzothiazole analogues designed to target D 4 R. We identified several compounds with high D 4 R binding affinity ( K i ≤ 6.9 nM) and >91-fold selectivity over other D 2 -like receptors (D 2 R, D 3 R) with diverse partial agonist and antagonist profiles. Novel analogue 16f is a potent low-efficacy D 4 R partial agonist, metabolically stable in rat and human liver microsomes, and has excellent brain penetration in rats (AUC brain/plasma > 3). 16f (5-30 mg/kg, i.p.) dose-dependently decreased iv cocaine self-administration in rats, consistent with previous results produced by D 4 R-selective antagonists. Off-target antagonism of 5-HT 2A or 5-HT 2B may also contribute to these effects. Results with 16f support further efforts to target D 4 R in SUD treatment.

Background: Effective management of metastatic disease requires multidisciplinary input and entails high risk of disease-related and treatment-related morbidity and mortality. The factors that influence clinician decision-making around spinal metastases are not well understood. We conducted a qualitative study that included a multidisciplinary cohort of physicians to evaluate the decision-making process for treatment of spinal metastases from the clinician's perspective., Methods: We recruited operative and nonoperative clinicians, including orthopaedic spine surgeons, neurosurgeons, radiation oncologists, and physiatrists, from across North America to participate in either a focus group or a semistructured interview. All interviews were audiorecorded and transcribed verbatim. We then performed a thematic analysis using all of the available transcript data. Investigators sequentially coded transcripts and identified recurring themes that encompass overarching patterns in the data and directly bear on the guiding study question. This was followed by the development of a thematic map that visually portrays the themes, the subthemes, and their interrelatedness, as well as their influence on treatment decision-making., Results: The thematic analysis revealed that numerous factors influence provider-based decision-making for patients with spinal metastases, including clinical elements of the disease process, treatment guidelines, patient preferences, and the dynamics of the multidisciplinary care team. The most prominent feature that resonated across all of the interviews was the importance of multidisciplinary care and the necessity of cohesion among a team of diverse health-care providers. Respondents emphasized aspects of care-team dynamics, including effective communication and intimate knowledge of team-member preferences, as necessary for the development of appropriate treatment strategies. Participants maintained that the primary role in decision-making should remain with the patient., Conclusions: Numerous factors influence provider-based decision-making for patients with spinal metastases, including multidisciplinary team dynamics, business pressure, and clinician experience. Participants maintained a focus on shared decision-making with patients, which contrasts with patient preferences to defer decisions to the physician, as described in prior work., Clinical Relevance: The results of this thematic analysis document the numerous factors that influence provider-based decision-making for patients with spinal metastases. Our results indicate that provider decisions regarding treatment are influenced by a combination of clinical characteristics, perceptions of patient quality of life, and the patient's preferences for care., Competing Interests: Disclosure: This research was funded by National Institutes of Health (NIH-NIAMS) grants K23-AR071464 to Dr. Schoenfeld, K24-AR057827 to Dr. Losina, and P30-AR072577 to Drs. Katz and Losina. On the Disclosure of Potential Conflicts of Interest forms, which are provided with the online version of the article, one or more of the authors checked “yes” to indicate that the author had a relevant financial relationship in the biomedical arena outside the submitted work (http://links.lww.com/JBJS/G182)., (Copyright © 2020 by The Journal of Bone and Joint Surgery, Incorporated.)

Study Objective: Emergency department (ED) visits provide an important opportunity for elder abuse identification. Our objective was to assess the accuracy of the ED Senior Abuse Identification (ED Senior AID) tool for the identification of elder abuse., Methods: We conducted a study of the ED Senior AID tool in 3 US EDs. Participants were English-speaking patients 65 years old and older who provided consent or for whom a legally authorized representative provided consent. Research nurses administered the screening tool, which includes a brief mental status assessment, questions about elder abuse, and a physical examination for patients who lack the ability to report abuse or for whom the presence or absence of abuse was uncertain. The reference standard was based on the majority opinion of a longitudinal, expert, all data (LEAD) panel following review and discussion of medical records, clinical social worker notes, and a structured social and behavioral evaluation. For the reference standard, LEAD panel members were blinded to the results of the screening tool., Results: Of 916 enrolled patients, 33 (3.6%) screened positive for elder abuse. The LEAD panel reviewed 125 cases: all 33 with positive screen results and a 10% random sample of negative screen results. Of these, the panel identified 17 cases as positive for elder abuse, including 16 of the 33 cases that screened positive. The ED Senior AID tool had a sensitivity of 94.1% (95% confidence interval [CI] 71.3% to 99.9%) and specificity of 84.3% (95% CI 76.0% to 90.6%)., Conclusion: This multicenter study found the ED Senior AID tool to have a high sensitivity and specificity as a screening tool for elder abuse, albeit with wide CIs., (Copyright © 2020 American College of Emergency Physicians. Published by Elsevier Inc. All rights reserved.)

The yam bean ( Pachyrizhus spp ) was recently introduced as a root crop with high-yield potential, considerable protein and micro-nutrient concentration to investigate its potential for food production in Rwanda. Except for Chuin types ( Pachyrizhus tuberosus ) which have high storage root dry matter (RDM) (26 to 36%), most accessions are consumed raw and are reported to have low RDM. The present study aimed to evaluate and identify adapted high yielding yam bean accessions in major agro-ecological zones of Rwanda. Field experiments with 22 accessions were conducted in 2012 at three research sites representing the major agro-ecologies of Rwanda. Strict reproductive pruning was followed to enhance fresh storage root yields. Across locations, ANOVA indicated highly significant differences ( p  < 0.01) for genotypes (G), locations (L), seasons (S) and G x L effects for storage root yield, vine yield and harvest index and accounted for 21.88%, 43.41%, 1.43% and 13.25% of the treatment sum of squares, respectively. The GGE bi-plot revealed that EC209018 is high yielding but unstable. However, genotypes, AC209034, AC209035 and EC209046, were outstanding in terms of adaptation and relative stability across the 3 locations, suggesting consistent root yields irrespective of location and environmental conditions. The GGE scatter plot showed that all genotypes formed one mega-environment for storage root yield (Karama, Musanze and Rubona) and two mega-environments for biomass yield (Karama and Rubona as one mega-environment and Musanze the second one). This study revealed that Karama is the most suitable environment for evaluation and selection of yam bean for yield components in Rwanda.

Mechanical properties of repairs of the piriformis tendon to the proximal femur were examined in a cadaveric model. Four constructs were separately tested: a suture anchor in the proximal femur, the anchor to suture interface, the suture in tendon interface, and a bone bridge style repair. The weakest interface was the anchor in the bone in cases in which the bone quality was poor. In specimens with high bone quality, the weakest interface was the suture in the anchor. A positive correlation was seen between Singh score for each femur and failure load of the anchor-bone constructs. Therefore, repairing the short external rotators after procedures involving a posterior approach to the hip may be warranted in patients with good bone quality.