Epidermal growth factor receptor exposed to cigarette smoke is aberrantly activated and undergoes perinuclear trafficking.

Exposure to hydrogen peroxide (H2O2), one of the reactive oxidants in the gas phase of cigarette smoke (CS), induces aberrant phosphorylation of the epidermal growth factor receptor (EGFR), resulting in the lack of ubiquitination by c-Cbl, and impaired degradation. EGFR activation without the feedback regulation of normal degradation leads to uncontrolled cell growth and tumor promotion. Using immunoprecipitation, immunoblotting, and confocal microscopy, we now demonstrate that the pattern of EGFR activation by CS is similar to H2O2. We found that exposure of human airway epithelial cells to CS, as with exposure to H2O2, not only results in an increase in EGFR activation over time, but the EGFR activated by H2O2 or CS is neither ubiquitinated nor subsequently degraded due to its inability to bind the E3 ubiquitin ligase, c-Cbl, either directly or indirectly via the Grb2 adapter protein. Moreover, the stabilized H2O2- and CS-activated EGFR remains plasma membrane-bound, while a population of the receptor is trafficked to a perinuclear region. Concomitantly, CS exposure results in the activation of downstream Akt and ERK1/2 survival and proliferation pathways. Therefore, exposure to CS, like exposure to H2O2, results in prolonged signaling by the EGFR and may contribute to uncontrolled lung cell growth.

How do novices learn physical examination skills? A systematic review of the literature.

BACKGROUND: Physical Examination (PE) skills are vital for patient care, and many medical students receive their first introduction to them in their pre-clinical years. A substantial amount of curriculum time is devoted to teaching these skills in most schools. Little is known about the best way to introduce PE skills to novice learners. OBJECTIVE: Our objective was to conduct a systematic review of how medical students are first taught PE skills and the evidence supporting these strategies. DESIGN: We searched ERIC, SCOPUS, MEDLINE, PubMed and EMBASE for descriptions of complete PE curricula for novice learners. Inclusion criteria were: (1) English language; (2) subjects were enrolled in medical school and were in the preclinical portion of their training; (3) description of a method to teach physical examination skills for the first time; (4) description of the study population; (5) Description of a complete PE curriculum. We used the Medical Education Research Study Quality Instrument (MERSQI) score to evaluate the quality of evidence provided. RESULTS: Our search returned 5,418 articles; 32 articles met our inclusion criteria. Two main types of curricula were reported: comprehensive 'head-to-toe' PE curricula (18%) and organ system-based curricula (41%). No studies compared these directly, and only two evaluated trainees' clinical performance. The rest of the articles described interventions used across curricula (41%). Median MERSQI score was 10.1 Interquartile range 8.1-12.4. We found evidence for the use of non-faculty teaching associates, technology-enhanced PE education, and the addition of clinical exposure to formal PE teaching. CONCLUSIONS: The current literature on teaching PE is focused on describing innovations to head-to-toe and organ system-based curricula rather than their relative effectiveness, and is further limited by its reliance on short-term outcomes. The optimal strategy for novice PE instruction remains unknown.

Heart Rate Variability and Acute Stress Among Novice Airway Managers.

BACKGROUND: The nature of medical emergencies places emergency physicians at risk for high levels of acute psychological stress (APS). Stress-modifying techniques like visualization, breath control, and mental practice may help mitigate APS, but objective markers of stress are difficult to measure in the clinical setting. We explored the relationship between heart rate variability (HRV), a real-time measure of autonomic arousal, and self-reported APS among emergency medicine (EM) residents learning to intubate on actual patients. METHODS: This was a prospective study of postgraduate year 1 (PGY-1) EM residents at a single academic medical center during their 1-month anesthesia rotation. We obtained repeated measures of HRV immediately before and during the first intubation attempt each day. Participants completed the modified Spielberger State-Trait Anxiety Inventory (STAI-6) before intubation attempts and scored intubation difficulty using the Intubation Difficulty Scale. We analyzed HRV using root mean square of successive differences and analyzed data using clustered data methods and Pearson correlation coefficients. RESULTS: We enrolled eight PGY-1 residents and recorded 64 intubations. Mean HRV in the 2 minutes before intubation (17.88 ± 9.22) and during intubation (21.17 ± 13.46) was significantly lower than resting baseline (32.09 ± 15.23; adjusted mean difference [95% CI] = -13.90 [-20.35 to -7.45], p < 0.001; and -10.77 [-17.65 to -3.88], p = 0.02). Preintubation anxiety was negatively correlated with HRV (r = -0.39 [-0.58 to -0.16], p = 0.001). Intubation difficulty was not significantly correlated with HRV (r = -0.12 [-0.36 to 0.13], p = 0.35). CONCLUSIONS: HRV shows promise as a real-time index of autonomic arousal and may serve as an outcome measure in the evaluation of stress-modifying interventions.

Pharmacologic Treatment of Cannabinoid Hyperemesis Syndrome: A Systematic Review.

Cannabinoid hyperemesis syndrome (CHS) has become more prevalent with increasing cannabis use. CHS is often resistant to standard antiemetics. The objective of this study is to review the current evidence for pharmacologic treatment of CHS. Medline, PsycINFO, DARE, OpenGrey, Google Scholar, and the Cochrane Library were searched from inception to February 2017. Articles were selected and reviewed independently. Evidence was graded using Oxford Center for Evidence-Based Medicine guidelines. The search resulted in 1262 articles with 63 of them eligible for inclusion (205 human subjects). There were 4 prospective level-2, 3 retrospective level-3 studies, 12 level-4 case series, and 44 level-5 case reports. Among level-2 studies (64 subjects), tricyclic antidepressants (TCAs) and lorazepam were discussed as effective long- and short-term treatments, respectively, in two studies. Ondansetron, promethazine, diphenhydramine, and opioids were also mentioned, but the authors did not comment on their efficacy. Among level-3 studies (43 subjects), one reported effective treatment with antiepileptics zonisamide and levetiracetam, but not TCAs. Another reported favorable response to morphine, ondansetron, and lorazepam but did not specify the actual number of patients receiving specific treatment. Among the level-4 case series (54 subjects), benzodiazepines, haloperidol, and capsaicin were reported as helpful. For level-5 case reports (44 subjects), benzodiazepines, metoclopramide, haloperidol, ondansetron, morphine, and capsaicin were reported as effective. Effective treatments mentioned only once included fentanyl, diazepam, promethazine, methadone, nabilone, levomepromazine, piritramide, and pantoprazole. Hot showers and baths were cited in all level-4 and -5 articles as universally effective. High-quality evidence for pharmacologic treatment of CHS is limited. Benzodiazepines, followed by haloperidol and capsaicin, were most frequently reported as effective for acute treatment, and TCAs for long-term treatment. As the prevalence of CHS increases, future prospective trials are greatly needed to evaluate and further define optimal pharmacologic treatment of patients with CHS.