Chloride-dependent mechanisms of multimodal sensory discrimination and nociceptive sensitization in Drosophila.

Individual sensory neurons can be tuned to many stimuli, each driving unique, stimulus-relevant behaviors, and the ability of multimodal nociceptor neurons to discriminate between potentially harmful and innocuous stimuli is broadly important for organismal survival. Moreover, disruptions in the capacity to differentiate between noxious and innocuous stimuli can result in neuropathic pain. Drosophila larval class III (CIII) neurons are peripheral noxious cold nociceptors and innocuous touch mechanosensors; high levels of activation drive cold-evoked contraction (CT) behavior, while low levels of activation result in a suite of touch-associated behaviors. However, it is unknown what molecular factors underlie CIII multimodality. Here, we show that the TMEM16/anoctamins subdued and white walker (wwk; CG15270) are required for cold-evoked CT, but not for touch-associated behavior, indicating a conserved role for anoctamins in nociception. We also evidence that CIII neurons make use of atypical depolarizing chloride currents to encode cold, and that overexpression of ncc69-a fly homologue of NKCC1-results in phenotypes consistent with neuropathic sensitization, including behavioral sensitization and neuronal hyperexcitability, making Drosophila CIII neurons a candidate system for future studies of the basic mechanisms underlying neuropathic pain.

Identification of a neural basis for cold acclimation in Drosophila larvae.

Low temperatures can be fatal to insects, but many species have evolved the ability to cold acclimate, thereby increasing their cold tolerance. It has been previously shown that Drosophila melanogaster larvae perform cold-evoked behaviors under the control of noxious cold-sensing neurons (nociceptors), but it is unknown how the nervous system might participate in cold tolerance. Herein, we describe cold-nociceptive behavior among 11 drosophilid species; we find that the predominant cold-evoked larval response is a head-to-tail contraction behavior, which is likely inherited from a common ancestor, but is unlikely to be protective. We therefore tested the hypothesis that cold nociception functions to protect larvae by triggering cold acclimation. We found that Drosophila melanogaster Class III nociceptors are sensitized by and critical to cold acclimation and that cold acclimation can be optogenetically evoked, sans cold. Collectively, these findings demonstrate that cold nociception constitutes a peripheral neural basis for Drosophila larval cold acclimation.

Does Formal Training in Medical Education and Professional Development Lead to Better Career Outcomes for Clinician Educators?

OBJECTIVES: Medical school and residency training programs rely on skilled clinician-educators to provide high-quality educational experiences. In 2002, the University of Pittsburgh's Institute for Clinical Research Education created a master's-level degree-granting program in medical education, which now has more than a decade of graduates. METHODS: All graduates between 2004 and 2014 were invited to complete an anonymous electronic survey regarding their experiences with the program and their perception of whether the master's program adequately prepared them in domains pertinent to medical educators. Participants also were asked to upload their current curricula vitae (CV) to assess objective measures of academic productivity among program graduates. RESULTS: More than 75% of surveys were completed (47/60) and 75% of CVs were submitted (45/60). Demographics of respondents showed that 66% were woman. The racial demographics of respondents revealed 13% Hispanic/Latino, 28% Asian, and 59% white, respectively. More than 90% of respondents agreed that because they completed the program, they were competent in multiple teaching and learning domains; 94% of respondents believed that they were more effective educators than peers who did not complete this degree. CV abstraction revealed that 98% of respondents currently held academic positions. Number of publications and number of years since program graduation were used to determine the rate of productivity of the graduates. Twenty-six graduates (58%) successfully published at least one peer-reviewed article per year since they graduated. This equated to approximately 3.77 publications per year for these 26 respondents and 2.27 publications per year for the entire cohort. CONCLUSIONS: Program graduates attributed their competence in several key domains that are crucial to excellence as a clinician-educator to their participation in the degree-granting program. The results of this study suggest that receipt of a graduate-level degree in medical education develops and enhances teaching skills and academic productivity among clinician-educators.

A Qualitative Analysis of Resident Adverse Event Reporting: What's Holding Us Back.

This study utilized focus groups of residents, who report adverse events at differing rates depending on their hospital site, to better understand barriers to residents' reporting and identify modifiable aspects of an institution's culture that could encourage resident event reporting. Focus groups included residents who rotated at 3 hospitals and represented 4 training programs. Focus groups were audio recorded and analyzed using qualitative methods. A total of 64 residents participated in 8 focus groups. Reporting behavior varied by hospital culture. Residents worried about damage to their professional relationships and lacked insight into the benefits of multiple reports of the same event or how human factors engineering can prevent errors. Residents did not understand how reporting affects litigation. Residents at other academic institutions likely experience similar barriers. This study illustrates that resident reporting is modifiable by changing hospital culture, but hospitals have only a few opportunities to mishandle reporting before resident reporting attitudes solidify.

Free Clinic Patients' Perceptions and Barriers to Applying for Health Insurance After Implementation of the Affordable Care Act.

Despite implementation of the Affordable Care Act (ACA), many Americans remain uninsured and receive care in free clinics. It is unknown what free clinic attendees in Pennsylvania know about health insurance expansion or what they perceive as barriers in enrolling in health insurance. The objective of this study was to assess the perceptions and experiences of free clinic patients from southwestern Pennsylvania when applying for health insurance after implementation of the ACA. We designed and implemented a survey of patients at three free clinics within Allegheny County, Pennsylvania from September 2016 to February 2017. Our survey included 22-items, 7 sociodemographic questions and 15 questions regarding the patient's health status and their perspectives related to obtaining health insurance. Data was obtained from 203 patient surveys; 110 (55.3%) of the respondents were men and 99 (48.8%) were African American. There were 48 respondents (24.1%) who did not report any income at the time of the study, and of those that did report an income, 92 (46.2%) respondents reported an income below 133% of the federal poverty level. The main barriers patients faced when applying for health insurance were: (1) lack of knowledge about health insurance (n = 127, 58.1%), (2) cost of health coverage (n = 85, 41.9%), (3) lack of resources (n = 83, 40.4%), and (4) lack of enrollment documentation (n = 43, 23.8%). Significant work is needed to better educate patients about their eligibility and options for health insurance. Free clinics can play a key role in eliminating barriers to health insurance enrollment.

Encouraging Resident Adverse Event Reporting: A Qualitative Study of Suggestions from the Front Lines.

INTRODUCTION: Little is known about what motivates residents to report adverse events. The goals of the qualitative study were to: (1) better understand facilitators to residents' event reporting and (2) identify effective interventions that encourage residents to report. METHODS: The authors conducted focus groups of upper-level residents from 4 training programs (2 internal medicine, a pediatric, and a combined medicine-pediatric) who rotated at 3 institutions within a large healthcare system in 2016. Quantitative data on reporting experience were gathered. Focus groups were audio recorded and transcribed. Two coders reviewed transcripts using the editing approach and organized codes into themes. RESULTS: Sixty-four residents participated in 8 focus groups. Residents were universally exposed to reportable events and knew how to report. Residents' reporting behavior varied by site according to local culture, with residents filing more reports at the pediatric hospital compared to other sites, but all groups expressed similar general views about facilitators to reporting. Facilitators included familiarity with the investigation process, reporting via telephone, and routine safety educational sessions with safety administrators. Residents identified specific interventions that encouraged reporting at the pediatric hospital, including incorporating an attending physician review of events into sign-out and training on error disclosure. CONCLUSIONS: This study provides insight into what motivates resident event reporting and describes concrete interventions to increase reporting. Our findings are consistent with the Theoretical Domains Framework of behavioral change. These strategies could prove successful at other pediatric hospitals to build a culture that values reporting and prepares residents as patient safety champions.

Drosophila menthol sensitivity and the Precambrian origins of transient receptor potential-dependent chemosensation.

Transient receptor potential (TRP) cation channels are highly conserved, polymodal sensors which respond to a wide variety of stimuli. Perhaps most notably, TRP channels serve critical functions in nociception and pain. A growing body of evidence suggests that transient receptor potential melastatin (TRPM) and transient receptor potential ankyrin (TRPA) thermal and electrophile sensitivities predate the protostome-deuterostome split (greater than 550 Ma). However, TRPM and TRPA channels are also thought to detect modified terpenes (e.g. menthol). Although terpenoids like menthol are thought to be aversive and/or harmful to insects, mechanistic sensitivity studies have been largely restricted to chordates. Furthermore, it is unknown if TRP-menthol sensing is as ancient as thermal and/or electrophile sensitivity. Combining genetic, optical, electrophysiological, behavioural and phylogenetic approaches, we tested the hypothesis that insect TRP channels play a conserved role in menthol sensing. We found that topical application of menthol to Drosophila melanogaster larvae elicits a Trpm- and TrpA1-dependent nocifensive rolling behaviour, which requires activation of Class IV nociceptor neurons. Further, in characterizing the evolution of TRP channels, we put forth the hypotheses that three previously undescribed TRPM channel clades (basal, αTRPM and ßTRPM), as well as TRPs with residues critical for menthol sensing, were present in ancestral bilaterians. This article is part of the Theo Murphy meeting issue 'Evolution of mechanisms and behaviour important for pain'.

Aspergillus aortitis in an immunocompetent patient presenting with acute endophthalmitis.

Aspergillus is a common environmental mold most often recognized as an infectious agent in patients with severe immune compromise. We present a case of an immunocompetent patient presenting with endogenous endophthalmitis in the absence of other infectious symptoms. The search for a systemic source revealed an ascending aortic pseudoaneurysm. Surgical resection and pathology revealed angioinvasive aspergillus aortitis. Recent cardiac surgery has been noted to be a risk factor for angioinvasive aspergillosis. Diagnosis is difficult as symptoms are mild and laboratory studies are often normal. To our knowledge this is the first case of aspergillus aortitis presenting as endogenous endophthalmitis without systemic signs of inflammation. These patients have a high mortality rate therefore early recognition is essential. It is important to consider angioinvasive aspergillus infections in patients with prior cardiac surgery presenting with occult embolic phenomena. Only with early diagnosis and prompt treatment can we improve outcomes of this disease process.