What is Effective in Massage Therapy? Well, "It Depends ": a Qualitative Study of Experienced Orthopaedic Massage Therapists.

Background: Massage has been used as a treatment for musculoskeletal pain throughout history and across cultures, and yet most meta-analyses have only shown weak support for the efficacy of massage. There is a recognised need for more research in foundational questions including: how massage treatments are constructed; what therapists actually do within a treatment, including their clinical reasoning; and what role therapists play in determining the effectiveness of a massage treatment. Purpose: The aim of this study was to explore what experienced orthopaedic massage therapists consider to be the aspects of their work that contribute to effectiveness. Setting and Participants: Semi-structured interviews were conducted via Zoom with six experienced orthopaedic massage therapists in Australia. Research Design: The interviews were analysed using inductive thematic analysis, seeking insights that might be practically applied, rather than theory-driven interpretations. Results: The participants focused on the underlying differences between clients, between therapists, and between treatments, and clearly indicated that this concept of "difference" was foundational to their view of their work and was the underlying context for the comments they made. Within that frame of "difference", three key themes were interpreted from the data: (1) "Everyone is different so every treatment is different": how they individualised treatment based on these differences; (2) "How therapists cope with difference": how they managed the challenges of working in this context; and (3) "What makes a difference": the problem-solving processes they used to target each treatment to meeting the client's needs. Conclusions: Participants did not identify specific techniques or modalities as "effective" or not. Rather, a therapist's ability to provide effective treatment was based on an iterative process of treatment and assessment that allowed them to focus on the individual needs of the client. In this case "effectiveness" could be considered a process rather than a specific massage technique.

Erratum to "Impact of pharmacist intervention to deprescribe inappropriate aspirin therapy in an outpatient anticoagulation clinic at a community hospital" [Am. Heart J. Plus: Cardiol. Res. Pract. volume 17, May 2022, 100165].

[This corrects the article DOI: 10.1016/j.ahjo.2022.100165.].

Impact of pharmacist intervention to deprescribe inappropriate aspirin therapy in an outpatient anticoagulation clinic at a community hospital.

Study objective: This study describes a pharmacist-led process to identify and discontinue inappropriate aspirin in patients receiving concomitant anticoagulant therapy and to evaluate the effectiveness of the intervention. Setting: The study took place in an outpatient anticoagulation clinic within a small community hospital. Participants: Patients ≥40 years old on indefinite anticoagulation therapy for atrial fibrillation and/or venous thromboembolism were included. Design: This is a quality improvement initiative. Interventions: Utilizing the electronic medical record and patient interview, use and indication for daily aspirin therapy was confirmed. Prospectively collected patient demographics and past medical history were used to determine appropriateness of aspirin therapy. For patients identified as receiving inappropriate aspirin therapy, a fax was sent to the referring provider recommending aspirin discontinuation. Main outcome measures: To assess the effectiveness of the intervention, outcomes were retrospectively measured. The primary outcome was the percentage of "accepted" recommendations. Secondary outcomes included the prevalence, dosing, and indications for aspirin therapy. Results: Eighty (33 %) of 242 patients were on aspirin. Fifty-two patients with atrial fibrillation and/or venous thromboembolism were assessed and aspirin was deemed inappropriate in 22 patients. The provider agreed with deprescribing aspirin therapy in 45 %. The most common dose and indication of aspirin therapy was 81 mg (98 %) and primary prevention (40 %) respectively. Conclusions: In our small practice, pharmacist-led interventions were an effective means to recommend aspirin discontinuation in our identified patients. Further studies are needed to optimize a pharmacist's role and address the long-term effects of deprescription.

The Academy for Future Science Faculty: randomized controlled trial of theory-driven coaching to shape development and diversity of early-career scientists.

BACKGROUND: Approaches to training biomedical scientists have created a talented research community. However, they have failed to create a professional workforce that includes many racial and ethnic minorities and women in proportion to their representation in the population or in PhD training. This is particularly true at the faculty level. Explanations for the absence of diversity in faculty ranks can be found in social science theories that reveal processes by which individuals develop identities, experiences, and skills required to be seen as legitimate within the profession. METHODS/DESIGN: Using the social science theories of Communities of Practice, Social Cognitive Career Theory, identity formation, and cultural capital, we have developed and are testing a novel coaching-based model to address some of the limitations of previous diversity approaches. This coaching intervention (The Academy for Future Science Faculty) includes annual in-person meetings of students and trained faculty Career Coaches, along with ongoing virtual coaching, group meetings and communication. The model is being tested as a randomized controlled trial with two cohorts of biomedical PhD students from across the U.S., one recruited at the start of their PhDs and one nearing completion. Stratification into the experimental and control groups, and to coaching groups within the experimental arms, achieved equal numbers of students by race, ethnicity and gender to the extent possible. A fundamental design element of the Academy is to teach and make visible the social science principles which highly influence scientific advancement, as well as acknowledging the extra challenges faced by underrepresented groups working to be seen as legitimate within the scientific communities. DISCUSSION: The strategy being tested is based upon a novel application of the well-established principles of deploying highly skilled coaches, selected and trained for their ability to develop talents of others. This coaching model is intended to be a complement, rather than a substitute, for traditional mentoring in biomedical research training, and is being tested as such.

Cytoskeletal mechanics of proplatelet maturation and platelet release.

Megakaryocytes generate platelets by remodeling their cytoplasm into long proplatelet extensions, which serve as assembly lines for platelet production. Although the mechanics of proplatelet elongation have been studied, the terminal steps of proplatelet maturation and platelet release remain poorly understood. To elucidate this process, released proplatelets were isolated, and their conversion into individual platelets was assessed. This enabled us to (a) define and quantify the different stages in platelet maturation, (b) identify a new intermediate stage in platelet production, the preplatelet, (c) delineate the cytoskeletal mechanics involved in preplatelet/proplatelet interconversion, and (d) model proplatelet fission and platelet release. Preplatelets are anucleate discoid particles 2-10 µm across that have the capacity to convert reversibly into elongated proplatelets by twisting microtubule-based forces that can be visualized in proplatelets expressing GFP-ß1-tubulin. The release of platelets from the ends of proplatelets occurs at an increasing rate in time during culture, as larger proplatelets undergo successive fission, and is potentiated by shear.

Visualization of microtubule growth in living platelets reveals a dynamic marginal band with multiple microtubules.

The marginal band of microtubules maintains the discoid shape of resting blood platelets. Although studies of platelet microtubule coil structure conclude that it is composed of a single microtubule, no investigations of its dynamics exist. In contrast to previous studies, permeabilized platelets incubated with GTP-rhodamine-tubulin revealed tubulin incorporation at 7.9 (+/- 1.9) points throughout the coil, and anti-EB1 antibodies stained 8.7 (+/- 2.0) sites, indicative of multiple free microtubules. To pursue this result, we expressed the microtubule plus-end marker EB3-GFP in megakaryocytes and examined its behavior in living platelets released from these cells. Time-lapse microscopy of EB3-GFP in resting platelets revealed multiple assembly sites within the coil and a bidirectional pattern of assembly. Consistent with these findings, tyrosinated tubulin, a marker of newly assembled microtubules, localized to resting platelet microtubule coils. These results suggest that the resting platelet marginal band contains multiple highly dynamic microtubules of mixed polarity. Analysis of microtubule coil diameters in newly formed resting platelets indicates that microtubule coil shrinkage occurs with aging. In addition, activated EB3-GFP-expressing platelets exhibited a dramatic increase in polymerizing microtubules, which travel outward and into filopodia. Thus, the dynamic microtubules associated with the marginal band likely function during both resting and activated platelet states.

Angiogenesis is regulated by a novel mechanism: pro- and antiangiogenic proteins are organized into separate platelet alpha granules and differentially released.

Platelets, in addition to their function in hemostasis, play an important role in wound healing and tumor growth. Because platelets contain angiogenesis stimulators and inhibitors, the mechanisms by which platelets regulate angiogenesis remain unclear. As platelets adhere to activated endothelium, their action can enhance or inhibit local angiogenesis. We therefore suspected a higher organization of angiogenesis regulators in platelets. Using double immunofluorescence and immunoelectron microscopy, we show that pro- and antiangiogenic proteins are separated in distinct subpopulations of alpha-granules in platelets and megakaryocytes. Double immunofluorescence labeling of vascular endothelial growth factor (VEGF) (an angiogenesis stimulator) and endostatin (an angiogenesis inhibitor), or for thrombospondin-1 and basic fibroblast growth factor, confirms the segregation of stimulators and inhibitors into separate and distinct alpha-granules. These observations motivated the hypothesis that distinct populations of alpha-granules could undergo selective release. The treatment of human platelets with a selective PAR4 agonist (AYPGKF-NH(2)) resulted in release of endostatin-containing granules, but not VEGF-containing granules, whereas the selective PAR1 agonist (TFLLR-NH(2)) liberated VEGF, but not endostatin-containing granules. In conclusion, the separate packaging of angiogenesis regulators into pharmacologically and morphologically distinct populations of alpha-granules in megakaryocytes and platelets may provide a mechanism by which platelets can locally stimulate or inhibit angiogenesis.

Mechanisms of organelle transport and capture along proplatelets during platelet production.

Megakaryocytes generate platelets by remodeling their cytoplasm into long proplatelet extensions, which serve as assembly lines for platelet production. Platelet packaging and release concludes at the tips of each proplatelet. Essential in this process is the distribution of organelles and platelet-specific granules into the nascent platelets. To investigate the mechanism of delivery of organelles into putative platelets, the distribution and dynamics of organelles/granules was monitored. Individual organelles are sent from the cell body to the proplatelets where they move bidirectionally until they are captured at proplatelet ends. Movement occurs at approximately 0.2 microm/min, but pauses and changes in direction are frequent. At any given time, approximately 30% of organelles/granules are in motion. Actin poisons do not diminish organelle motion, and vesicular structures are intimately associated with the microtubules. Therefore, movement appears to involve microtubule-based forces. Bidirectional organelle movement is conveyed by the bipolar organization of microtubules within the proplatelet, as kinesin-coated beads move bidirectionally on the microtubule arrays of permeabilized proplatelets. Movement of organelles along proplatelets involves 2 mechanisms: organelles travel along microtubules, and the linked microtubules move relative to each other. These studies demonstrate that the components that form platelets are delivered to and assembled de novo along proplatelets.

Differential roles of microtubule assembly and sliding in proplatelet formation by megakaryocytes.

Megakaryocytes are terminally differentiated cells that, in their final hours, convert their cytoplasm into long, branched proplatelets, which remodel into blood platelets. Proplatelets elongate at an average rate of 0.85 microm/min in a microtubule-dependent process. Addition of rhodamine-tubulin to permeabilized proplatelets, immunofluorescence microscopy of the microtubule plus-end marker end-binding protein 3 (EB3), and fluorescence time-lapse microscopy of EB3-green fluorescent protein (GFP)-expressing megakaryocytes reveal that microtubules, organized as bipolar arrays, continuously polymerize throughout the proplatelet. In immature megakaryocytes lacking proplatelets, microtubule plus-ends initiate and grow by centrosomal nucleation at rates of 8.9 to 12.3 microm/min. In contrast, plus-end growth rates of microtubules within proplatelets are highly variable (1.5-23.5 microm/min) and are both slower and faster than those seen in immature cells. Despite the continuous assembly of microtubules, proplatelets continue to elongate when net microtubule assembly is arrested. One alternative mechanism for force generation is microtubule sliding. Triton X-100-permeabilized proplatelets containing dynein and its regulatory complex, dynactin, but not kinesin, elongate with the addition of adenosine triphosphate (ATP) at a rate of 0.65 microm/min. Retroviral expression in megakaryocytes of dynamitin (p50), which disrupts dynactin-dynein function, inhibits proplatelet elongation. We conclude that while continuous polymerization of microtubules is necessary to support the enlarging proplatelet mass, the sliding of overlapping microtubules is a vital component of proplatelet elongation.

Imaging diagnosis: pneumothorax and focal peritonitis in a dog due to migration of an inhaled grass awn.

A 1-year-old working Kelpie developed pneumothorax and focal peritonitis after inhalation of a grass awn that migrated from the lung, through the diaphragm, into the peritoneal cavity. Radiographic evidence of sternal lymph node enlargement was fundamental in the diagnosis of intraperitoneal disease and prompted abdominal ultrasound leading to definitive diagnosis.