Scaling of Primate Forearm Muscle Architecture as It Relates to Locomotion and Posture.

It has been previously proposed that distal humerus morphology may reflect the locomotor pattern and substrate preferred by different primates. However, relationships between these behaviors and the morphological capabilities of muscles originating on these osteological structures have not been fully explored. Here, we present data about forearm muscle architecture in a sample of 44 primate species (N = 55 specimens): 9 strepsirrhines, 15 platyrrhines, and 20 catarrhines. The sample includes all major locomotor and substrate use groups. We isolated each antebrachial muscle and categorized them into functional groups: wrist and digital extensors and flexors, antebrachial mm. that do not cross the wrist, and functional combinations thereof. Muscle mass, physiological cross-sectional area (PCSA), reduced PCSA (RPCSA), and fiber length (FL) are examined in the context of higher taxonomic group, as well as locomotor/postural and substrate preferences. Results show that muscle masses, PCSA, and RPCSA scale with positive allometry while FL scales with isometry indicating that larger primates have relatively stronger, but neither faster nor more flexible, forearms across the sample. When accounting for variation in body size, we found no statistically significant difference in architecture among higher taxonomic groups or locomotor/postural groups. However, we found that arboreal primates have significantly greater FL than terrestrial ones, suggesting that these species are adapted for greater speed and/or flexibility in the trees. These data may affect our interpretation of the mechanisms for variation in humeral morphology and provide information for refining biomechanical models of joint stress and movement in extant and fossil primates. Anat Rec, 301:484-495, 2018. © 2018 Wiley Periodicals, Inc.

A breath of fresh air: A family ceremony.

Healing rituals and ceremonies are conducted with the hope of ushering a sick or impaired person back to wellness or preserving health against perceived threats (Burns, 1996). In medical settings, healing ceremonies can address biopsychosocial, existential, and spiritual aspects of difficult situations (Hammerschlag, 1989; Johnson, Feldman, Lubin, & Southwick, 1995; Mehl-Madrona, 1999). This article describes presents the case history of Lisa H. and her son, Anthony. Anthony experienced two medical crises within the first five days of his birth. The author suggested a healing ceremony might be valuable for Anthony's family. The ceremony opened the door to a candid conversation regarding everything that had transpired. It decreased the family's fear, anxiety, frustration, and guilt, and helped them cope better with the situation. Anthony sailed smoothly through his surgery and went home from the hospital a week later. The author notes that health care professionals generally set aside their spirituality while trying to help people, thus broaching the subject of ceremonies might make the care provider or the family feel uncomfortable. Care providers who are uncomfortable with participating could still provide a valuable service by presenting the notion of a ceremony as an option the patient or family may wish to consider, and directing them to useful resources.

Almond "Appetizer" Effect on Glucose Tolerance Test (GTT) Results.

BACKGROUND: The extent to which glucose intolerance can be acutely improved with dietary modification is unclear. The purpose of this study was to test the effect of ingesting a low-calorie almond preload ("appetizer") 30 minutes before oral glucose tolerance testing in glucose-intolerant individuals without diabetes. METHODS: Twenty adults with prediabetes or isolated 1-hour glucose ≥160 mg/dL underwent 2 fasting oral glucose tolerance tests (GTTs)-1 standard GTT and 1 GTT 30 minutes after eating a half ounce (12) of dry-roasted almonds. Fourteen participants met 1 or more prediabetes diagnostic criteria; 6 had only elevated 1-hour glucose ≥160 mg/dL. RESULTS: The mean 1-hour plasma glucose after the almond preload was 37.1 mg/dL (19.4%) lower (154.6 vs 191.7; P < .001) than in the standard GTT. The almond preload reduced the area under the glucose curve by 15.5% (P < .001). Eight individuals had a marked hypoglycemic effect (glucose reduced by 45 to 110 mg/dL); 4 had a moderate hypoglycemic effect (22-32 mg/dL). CONCLUSION: A low-calorie almond "appetizer" showed promise as an option for decreasing postprandial hyperglycemia in individuals with prediabetes or isolated 1-hour postprandial hyperglycemia. Further study is needed to confirm and refine the role of such a premeal appetizer in the self-care of prediabetes.

Evolution of preprofessional pharmacy curricula.

OBJECTIVES: To examine changes in preprofessional pharmacy curricular requirements and trends, and determine rationales for and implications of modifications. METHODS: Prerequisite curricular requirements compiled between 2006 and 2011 from all doctor of pharmacy (PharmD) programs approved by the Accreditation Council of Pharmacy Education were reviewed to ascertain trends over the past 5 years. An online survey was conducted of 20 programs that required either 3 years of prerequisite courses or a bachelor's degree, and a random sample of 20 programs that required 2 years of prerequisites. Standardized telephone interviews were then conducted with representatives of 9 programs. RESULTS: In 2006, 4 programs required 3 years of prerequisite courses and none required a bachelor's degree; by 2011, these increased to 18 programs and 7 programs, respectively. Of 40 programs surveyed, responses were received from 28 (70%), 9 (32%) of which reported having increased the number of prerequisite courses since 2006. Reasons given for changes included desire to raise the level of academic achievement of students entering the PharmD program, desire to increase incoming student maturity, and desire to add clinical sciences and experiential coursework to the pharmacy curriculum. Some colleges and schools experienced a temporary decrease in applicants. CONCLUSIONS: The preprofessional curriculum continues to evolve, with many programs increasing the number of course prerequisites. The implications of increasing prerequisites were variable and included a perceived increase in maturity and quality of applicants and, for some schools, a temporary decrease in the number of applicants.

Development and validation of a single-well cell-based assay for the detection of endogenous phosphoproteins.

We describe a cellular assay for detection of phosphorylation of endogenous proteins, whereby cells are seeded, treated, and assayed for modulation of phosphorylation in a single microplate well. The procedure is coupled to a rapid, one-wash sandwich enzyme-linked immuno-sorbent assay, enabling results to be obtained within 3-4 h from cell seeding. The assay was tested in two separate cellular systems, namely, HeLa and MCF-7 cells. When using the one-well protocol with Akt phosphorylation as a model, the response to a number of agonists was the same as the response obtained using cells treated in a separate microplate, using a conventional lysate transfer approach. The assay procedure was automated, and quantitative pharmacological data on three known inhibitors of the PI3-kinase signaling pathway was obtained within 4 h from seeding cells, with six dispense steps, and a single wash cycle. Thus, the protocol affords a reliable means of assaying for cellular signaling events in different cell types, and is amenable to automation.

Proton pump inhibitor therapy associated with lower glycosylated hemoglobin levels in type 2 diabetes.

INTRODUCTION: Oral hypoglycemic medications sometimes do not control type 2 diabetes well. Proton pump inhibitors (PPIs) as adjunctive therapy might improve diabetes control through increasing serum gastrin and fasting insulin levels. METHODS: Electronic medical records in a family medicine residency program office practice were reviewed for 73 individuals with type 2 diabetes (not taking insulin), for whom PPIs were prescribed. Values for glycosylated hemoglobin (HbA1c) for periods of time when a PPI had been prescribed were compared with HbA1c levels for periods of time with no record of PPI prescribing or over-the-counter PPI use. RESULTS: The mean HbA1c for patients not taking insulin was 7.11 during periods with recorded prescribing or over-the-counter use of PPIs, compared with 7.70 during periods without recorded PPI therapy (P = .001). Mean HbA1c for metformin monotherapy was not significantly different (6.81 with PPI vs. 7.10 without PPI; n = 16; P = .25). Mean HbA1c was significantly different for combination therapy that included metformin and/or sulfonylurea and/or giltazone (7.26 vs. 7.80; n = 27; P = .002). CONCLUSION: The observed association between PPI therapy and lower HbA1c levels suggests that PPIs may be useful as adjunctive therapy for type 2 diabetes.

G-protein-coupled receptor-mediated MAPK and PI3-kinase signaling is maintained in Chinese hamster ovary cells after γ-irradiation.

To expedite G-protein-coupled receptor (GPCR) drug screening studies, cell lines amenable to transfection (e.g. CHO cells) have been widely used as cellular models. These cells can be frozen in a ready-to-use format, allowing screening of a single batch of cells and validation of the cellular material prior to the screening run. A common method used to deliver frozen cells to screening programs is to γ-irradiate the cells, abrogating cell division after thawing and ensuring consistency in the number of cells analyzed per well. With the recognition that signaling proteins such as ERK and Akt are important markers of GPCR activation, along with the availability of suitable assays for their measurement, these outputs have become important for GPCR screening programs. Here we show that several γ-irradiated and frozen CHO-K1 cell lines expressing transfected GPCRs, initially optimized for performing cAMP or AequoScreen calcium flux assays, can be used for the measurement of GPCR-mediated ERK and Akt phosphorylation. Furthermore, CHO-K1 cells transfected with NOP or GAL(1) receptors show pharmacology for a number of agonists and antagonists that is consistent with non-irradiated cultured lines. These data indicate that γ-irradiated CHO-K1 cells can be reliably used for the measurement of GPCR-mediated kinase signaling outputs.

Promoting knowledge of statins in patients with low health literacy using an audio booklet.

BACKGROUND: Statins are generally well tolerated and effective at reducing a patient's risk of both primary and secondary cardiovascular events. Many patients who would benefit from statin therapy either do not adhere to or stop taking their statin medication within the first year. We developed an audio booklet targeted to low health literacy patients to teach them about the benefits and risks of statins to help the patients adhere to their statin therapy. METHODS: Through focus groups and an iterative design, an audio booklet was developed for both English-speaking and Spanish-speaking patients. We then compared the booklet with standard of care in 132 patients from our target patient population to measure its impact on knowledge and understanding of statins. RESULTS: The patients enjoyed the audio booklet and showed significant increases in knowledge after listening to it when compared with those who received the standard of care materials. CONCLUSION: The audio booklet shows promise as a tool that can be used effectively in clinical practice to teach patients about statin therapy.

P2Y12 receptor inhibitors: integrating ticagrelor into the management of acute coronary syndrome.

Acute coronary syndrome (ACS) is a continuum of disease that includes non-ST-segment elevation ACS and ST-segment elevation myocardial infarction. The purpose of this article is to define the developing role of ticagrelor in ACS and compare it to currently available P2Y12 receptor inhibitors. While clopidogrel remains the "workhorse" P2Y12 receptor inhibitor for many patients with ACS and prasugrel has an established role in select situations, clinicians must now assimilate the evolving role of ticagrelor. Although ticagrelor offers important advances in the management of ACS (eg, reversibility), there are also notable clinical considerations (eg, unique adverse effects such as dyspnea). Based on the current evidence, we propose an algorithm to aid clinicians in the selection of a P2Y12 receptor inhibitor for patients with ACS in various clinical situations.

An emerging role for kinase screening in GPCR drug discovery.

GPCRs are a large class of cell-surface receptors that are involved in a diverse array of biological processes, including many that are critical to diseases. As a result, GPCRs are a major focus for drug discovery research, and have been highly amenable to therapeutic intervention. However, the successes to date may represent the 'low-hanging fruit' (ie, outcomes that have been easiest to achieve). The signaling of many GPCRs is now recognized to be substantially more complex than initially thought. Thus, the traditional analysis of single GPCR-mediated secondary messengers for early-stage drug discovery, such as the measurement of Ca2+ or the formation of cAMP, may not provide all of the relevant signaling information on a target receptor or information on all of the effects of potential drugs. Given this complexity, the determination of other signaling events, such as the GPCR-mediated activation of major kinase pathways, including PI3K and MAPK, is likely to become increasingly important in the identification of indicators of GPCR function. Furthermore, the advent of highly efficient assays for detecting the GPCR-mediated activation of protein kinase targets allows this target class to be readily amenable to cell-based high-throughput screening programs.

Development of cell-based assays for cytokine receptor signaling, using an AlphaScreen SureFire assay format.

The signal transducers and activators of transcription (STAT) proteins are a small family of signaling proteins that are crucial for cytokine and growth factor receptor-mediated signaling in various blood cell types. Despite their central role in immune and hematopoietic cellular regulation, there are relatively few options for monitoring receptor-mediated JAK/STAT signaling events in a cell-based format, without the need for cellular transfections or labor intensive methodology. Indeed, traditional methods such as the Western blot or ELISA remain a standard method for determining the phosphorylation status of endogenous STAT proteins. Here we present data for the rapid detection of endogenous receptor-mediated phosphorylation of multiple STAT proteins using the bead-based AlphaScreen SureFire technology. With three different cell lines (human acute monocytic leukemia THP-1 cells, human erythroleukemic TF-1 cells, and human T lymphocytic Jurkat cells), we have optimized a rapid and homogeneous methodology for monitoring endogenous, receptor-mediated signaling via STAT 1, STAT 3, or STAT 5 phosphorylation, in response to several agonists. These assays, which can be tailored for both standard research applications or high-throughput drug screening applications, afford quantitative data for receptor-mediated signaling mechanisms in an endogenous, cellular environment.

Antithrombotic therapy for the CardioWest temporary total artificial heart.

The CardioWest temporary total artificial heart serves as a viable bridge to orthotopic heart transplantation in patients who are experiencing end-stage refractory biventricular heart failure. This device is associated with a low, albeit still substantial, risk of thrombosis. Platelet interactions with artificial surfaces are complex and result in continuous activation of contact proteins despite therapeutic anticoagulation. We searched the medical literature (publication dates, January 1962-October 2009) in order to evaluate means of mitigating adverse events that have occurred after implantation of the CardioWest temporary total artificial heart.We conclude that the use of a multitargeted antithrombotic approach, involving anticoagulation (bivalirudin and warfarin) and antiplatelet therapy (dipyridamole and aspirin), can mitigate the procoagulative effects of mechanical circulatory assist devices, particularly those that are associated with the CardioWest temporary total artificial heart. Careful monitoring with use of a variant multisystem approach, involving efficacy tests (thrombelastography and light transmittance aggregometry), safety tests (laboratory analyses), and warfarin genomics, may maximize the therapeutic actions and minimize the bleeding risks that are associated with the multitargeted antithrombotic approach. The development and monitoring of individualized antithrombotic regimens require that informed health professionals appreciate the complexities and grasp the hazards that are associated with these therapies.

Intrapericardial triamcinolone for acute pericarditis after electrophysiologic procedures.

PURPOSE: The use of intrapericardial triamcinolone for acute pericarditis after electrophysiologic procedures in three patients is described. SUMMARY: Treatment for idiopathic pericarditis and viral pericarditis, which account for about 85% of cases, focuses on pain management and decreasing pericardial inflammation. This is oftentimes achieved with nonsteroidal antiinflammatory drugs (NSAIDs). Colchicine may be used in combination with NSAIDs, specifically in postmyocardial infarction pericarditis and recurrent pericarditis. Because oral corticosteroid use has been shown to be an independent risk factor in pericarditis recurrence, their use in patients with refractory pericarditis is reserved as a last-resort option. Intrapericardial triamcinolone is an uncommon treatment approach, although it is recommended in select situations of pericarditis according to guidelines developed by the European Society of Cardiology. In this retrospective case series, three patients with pericarditis, tamponade, or both as a complication of radiofrequency ablation or implantable cardioverter defibrillator implantation received triamcinolone. The drug was instilled intrapericardially, with doses ranging from 50 to 200 mg. In two patients, the need for pain medication and the perceived pain score decreased dramatically after triamcinolone administration. In the third patient, triamcinolone administration decreased the need for supportive therapy but was not deemed a complete clinical success. Additional study is necessary to better define the use of intrapericardial triamcinolone and determine long-term outcomes associated with this therapy. Other factors, including past medical history and renal function, also need to be taken into account when choosing the proper dosing regimen. CONCLUSION: Intrapericardial administration of triamcinolone acetonide may be an effective treatment for patients with acute pericarditis after electrophysiologic procedures.

An advanced cardiovascular pharmacotherapy course blending online and face-to-face instruction.

OBJECTIVE: To assess the effectiveness of online instruction in a cardiology pharmacotherapy elective. DESIGN: Eight drug-focused lectures and 6 introductory presentations were added to a cardiology pharmacotherapy course. Students completed an online quiz after each online drug-focused lecture and scores were compared to quizzes taken at the beginning and end of the course, as well as on a cardiology advanced pharmacy practice experience (APPE). For online introductory presentations, students completed a quiz at the beginning of the next face-to-face session. A survey was conducted at the end of the course to obtain student feedback. ASSESSMENT: Compared to baseline scores, student learning was demonstrated after online drug-focused lectures by higher quiz scores attained immediately after completing the lecture, at the end of the course, and at the beginning of the APPE. Furthermore, students performed better on quizzes at the beginning of face-to-face sessions if they first completed an online introductory presentation. Students expressed strong support for the online components of the course. CONCLUSIONS: A blended learning environment with online and face-to-face instruction is an effective way to teach a cardiology pharmacotherapy elective. The online component of this course was well received by students, improved student preparation before attending class, and appeared to enhance long-term cardiovascular drug knowledge.

Cost-effectiveness analysis of anticoagulation strategies in non-ST-elevation acute coronary syndromes.

BACKGROUND: Contemporary studies document the outcomes of unfractionated heparin (UFH), enoxaparin, fondaparinux, and bivalirudin in patients with non-ST-elevation acute coronary syndrome (NSTE-ACS). It remains unclear which anticoagulant regimen is the most cost-effective. OBJECTIVE: To perform a cost-effectiveness analysis comparing 4 anticoagulant regimens in NSTE-ACS. METHODS: A decision analysis was conducted from a healthcare provider perspective. Data sources included the SYNERGY, OASIS-5, and ACUITY trials, including 2 subgroup analyses. A decision tree model was created incorporating the outcomes associated with 4 antithrombotic approaches: UFH with eptifibatide, enoxaparin with eptifibatide, bivalirudin alone, and fondaparinux with eptifibatide. The percentage of eptifibatide use in each arm was consistent with clinical trials. Probabilities of complications (eg, myocardial infarction, revascularization, major/minor bleeding at 30 days) were calculated. Costs were assigned to each outcome, incorporating the cost associated with diagnosis-related group and/or current procedural terminology codes, drug acquisition, and red blood cell infusions. Multiple sensitivity analyses were performed. RESULTS: The base case analysis showed bivalirudin monotherapy to be the least costly regimen ($1131 per average course), and it dominated enoxaparin plus eptifibatide ($1609) and UFH plus eptifibatide ($1739) in cost-effectiveness. The total average cost of fondaparinux with eptifibatide ($1184) was higher than bivalirudin alone, but the combination was more effective, resulting in an incremental cost of $2569 per each additional patient treated without complication. Sensitivity analyses showed the model's results to be sensitive to drug acquisition cost and complication probabilities. Probabilistic sensitivity analyses favored neither bivalirudin nor fondaparinux; however, when 2 or more vials of bivalirudin were necessary, bivalirudin was no longer a cost-effective alternative. CONCLUSIONS: Bivalirudin is the least costly agent in moderate- to high-risk NSTE-ACS patients managed with an early invasive approach, if its use is consistent with the ACUITY trial. Fondaparinux is the preferred agent in patients undergoing a conservative treatment strategy.

Successful use and dosing of bivalirudin after temporary total artificial heart implantation: a case series.

The temporary total artificial heart (TAH-t) has emerged as an effective bridge to transplantation for individuals with biventricular failure. Implantation of a TAH-t creates a hypercoagulable state requiring a multidrug approach that includes low-dose unfractionated heparin (UFH) in order to minimize thromboembolism. A concern with UFH is the development of heparin-dependent antibodies, which develop in up to 50% of patients receiving the drug as part of cardiopulmonary bypass. If UFH therapy continues postoperatively, the risk of heparin-induced thrombocytopenia approaches 3%. Small investigations have demonstrated that bivalirudin, given as a bolus of 0.75-1 mg/kg followed by an infusion at 1.75-2.5 mg/kg/hour, is an effective alternative to UFH for therapeutic anticoagulation during coronary artery bypass surgery, valve replacement, or both. We describe a series of five adults (age range 24-58 yrs) who received bivalirudin as an alternative to low-dose UFH after TAH-t implantation. None of the patients had documented heparin-induced thrombocytopenia. Treatment was started at the discretion of the treating physician, and adjustments were based principally on the results of thromboelastography. Additional general monitoring included activated partial thromboplastin time, prothrombin time, international normalized ratio, fibrinogen, D-dimer, platelet count, hemoglobin, hematocrit, and platelet aggregation studies. Bivalirudin therapy was continued until successful warfarin implementation. All five patients received bivalirudin in addition to standard antithrombotic therapy. Bivalirudin treatment started at a dosage of 0.005 or 0.01 mg/kg/hour with titration to maintain normocoagulability, which occurred (without concomitant warfarin therapy) within the dosage range of 0.01-0.02 mg/kg/hour. Duration of TAH-t implantation was a mean of 38.8 days (range 25-60 days), and bivalirudin was continued for a mean of 15.2 days (range 7-24 days). No major hemorrhagic events occurred during treatment, and all patients successfully transitioned to warfarin therapy. Low-dose bivalirudin, as an alternative to UFH, maintained normocoagulability after TAH-t implantation. Further investigation is warranted to define the role and dosing of bivalirudin in this situation.