SUMMARY At the cellular level, α-tubulin acetylation alters the structure of microtubules to render them mechanically resistant to compressive forces. How this biochemical property of microtubule acetylation relates to mechanosensation remains unknown, although prior studies have shown that microtubule acetylation influences touch perception. Here, we identify the major Drosophila α-tubulin acetylase (dTAT) and show that it plays key roles in several forms of mechanosensation. dTAT is highly expressed in the larval peripheral nervous system (PNS), but it is largely dispensable for neuronal morphogenesis. Mutation of the acetylase gene or the K40 acetylation site in α-tubulin impairs mechanical sensitivity in sensory neurons and behavioral responses to gentle touch, harsh touch, gravity, and vibration stimuli, but not noxious thermal stimulus. Finally, we show that dTAT is required for mechanically induced activation of NOMPC, a microtubule-associated transient receptor potential channel, and functions to maintain integrity of the microtubule cytoskeleton in response to mechanical stimulation.

Dendrites exhibit enormous diversity in form and can differ in size by several orders of magnitude even in a single animal. However, whether neurons with large dendrite arbors have specialized mechanisms to support their growth demands is unknown. To address this question, we conducted a genetic screen for mutations that differentially affected growth in neurons with different-sized dendrite arbors. From this screen, we identified a mutant that selectively affects dendrite growth in neurons with large dendrite arbors without affecting dendrite growth in neurons with small dendrite arbors or the animal overall. This mutant disrupts a putative amino acid transporter, Pathetic (Path), that localizes to the cell surface and endolysosomal compartments in neurons. Although Path is broadly expressed in neurons and nonneuronal cells, mutation of path impinges on nutrient responses and protein homeostasis specifically in neurons with large dendrite arbors but not in other cells. Altogether, our results demonstrate that specialized molecular mechanisms exist to support growth demands in neurons with large dendrite arbors and define Path as a founding member of this growth program.

Supplemental Digital Content is Available in the Text.An analysis of a nationwide data set shows opioid prescriptions by dentists are associated with adverse outcomes and persistent opioid use, even when prescribed within recommendations.

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Studies evaluating the cost-effectiveness of clinical pharmacy services (CPS) are needed to justify implementation and reimbursement. Through a systematic review, we describe services provided by pharmacists and their economic outcomes. We conducted a literature search of published studies in PubMed, Ovid, and Embase from January 2011 through December 2017. Manuscripts evaluating a CPS with patient-level economic outcomes and conducted in the United States were included. Study risks of bias were classified by study design characteristics. Economic evaluations were classified according to the presence of a comparator, and cost and outcome measures included. The quality of full economic evaluations was assessed using the Quality of Health Economic Studies (QHES) instrument. Descriptive statistics were used to summarize CPS characteristics. After screening, 115 studies wereincluded. Type of service provided included general pharmacotherapy (41%), disease management (30%), and targeted drug program (17%). Settings included hospital (34%), ambulatory care (28%), and community pharmacy (17%). Study designs were considered high risk of bias (use of a historical control group or no control group) in 69% of cases while 25% were medium risk of bias (non-randomized with a concurrent control group) and 6% were low risk of bias (randomized experimental or multigroup interrupted time series). Economic evaluation types were descriptive studies that measured cost and/or outcomes of a CPS (55%), comparative studies that measured cost or outcomes of a CPS and a comparator (37%), and full evaluations that measured cost and outcomes of a CPS and a comparator (8%). Among nine full evaluations, the median (range) QHES score was 74 (59-95) and four reported the CPS as being more effective at a lower cost. Few full economic evaluations were conducted, but supported the cost-effectiveness of CPS. Use of a comparator group and measurement of economic inputs and outcomes would strengthen the body of evidence. K E Y W O R D Scost-benefit analysis, health services research, pharmacoeconomics, pharmacy