CB 1 Cannabinoid Receptor Agonists Induce Acute Respiratory Depression in Awake Mice.

Recreational use of synthetic cannabinoid agonists (i.e., "Spice" compounds) that target the Cannabinoid Type 1 receptor (CB 1 ) can cause respiratory depression in humans. However, Δ 9 -tetrahydrocannabinol (THC), the major psychoactive phytocannabinoid in cannabis, is not traditionally thought to interact with CNS control of respiration, based largely upon sparse labeling of CB1 receptors in the medulla and few reports of clinically significant respiratory depression following cannabis overdose. The respiratory effects of CB 1 agonists have rarely been studied in vivo , suggesting that additional inquiry is required to reconcile the conflict between conventional wisdom and human data. Here we used whole body plethysmography to examine the respiratory effects of the synthetic high efficacy CB 1 agonist CP55,940, and the low efficacy CB 1 agonist Δ 9 -tetrahydrocannabinol in male and female mice. CP55,940 and THC, administered systemically, both robustly suppressed minute ventilation. Both cannabinoids also produced sizable reductions in tidal volume, decreasing both peak inspiratory and expiratory flow - measures of respiratory effort. Similarly, both drugs reduced respiratory frequency, decreasing both inspiratory and expiratory time while markedly increasing expiratory pause, and to a lesser extent, inspiratory pause. Respiratory suppressive effects occurred at lower doses in females than in males, and at many of the same doses shown to produce cardinal behavioral signs of CB 1 activation. We next used RNAscope in situ hybridization to localize CB 1 mRNA to glutamatergic neurons in the medullary pre-Bötzinger Complex, a critical nucleus in controlling respiration. Our results show that, contrary to previous conventional wisdom, CB 1 mRNA is expressed in glutamatergic neurons in a brain region essential for breathing and CB 1 agonists can cause significant respiratory depression.

Voice and Airway Outcomes of Montgomery T-tube Placement in Laryngotracheal Stenosis.

OBJECTIVES: To describe voice and airway outcomes and complications experienced by patients with laryngotracheal stenosis following Montgomery T-tube placement. METHODS: Retrospective chart review of all patients with laryngotracheal stenosis and Montgomery T-tube placement treated at a tertiary referral center from 2012 to 2021. RESULTS: Eighteen patients met criteria with laryngotracheal stenosis, seven including the level of the glottis and 11 without glottal involvement. Eleven were completely aphonic before T-tube placement and the remainder had severe dysphonia. There was improvement of Voice Handicap Index-10, Reflux Symptom Index, and GRBAS grade following T-tube placement in patients compared to their preoperative values. Improvement of grade was greater in patients without glottal involvement. Complications of chronic indwelling T-tube included granulation in 14 patients (78%), tracheitis in two patients (11%), and mucus plugging in three patients (17%) with one T-tube related mortality. Five patients were eventually decannulated, six returned to tracheostomy tube, and seven retained the T-tube at last follow-up (average: 30 months, range: 4-80 months). CONCLUSIONS: Montgomery T-tube placement improves voice in patients with severe dysphonia secondary to laryngotracheal stenosis with and without glottal involvement though the degree of improvement is greater in patients without glottal involvement. T-tube can help reestablish long-term laryngotracheal continuity in patients with no other surgical options. The potential benefits in phonation should be weighed against the possibility of rare but serious adverse events.

Effects of Cough Suppression Therapy on Voice Disorder Severity.

OBJECTIVES//HYPOTHESIS: To determine changes in voice severity when treating chronic cough refractory to medical treatment with cough suppression therapy (CST) in patients with chronic cough and voice complaints. Chronic cough has been reported to be refractory to medical treatment and frequently co-occurs with voice disorders. The possible effects of CST on self-assessed changes in chronic cough and voice disorders have not been demonstrated. STUDY DESIGN: Retrospective analysis of the effects of cough suppression therapy (CST) on self-assessed changes in chronic cough and voice disorder severity in patients with both chronic cough and voice disorders. METHODS: Forty-three adult patients with the primary complaint of chronic refractory cough underwent pre- and post-treatment diagnostic examinations, completed pre- and post-treatment Voice Handicap Index-10 (VHI-10) and Cough Severity Index assessments, and were treated by a licensed speech-language pathologist using CST. Twenty-seven subjects were assigned to the cough (C) group and 16 to the cough-voice (CV) group based on the severity of their VHI-10 scores. RESULTS: Post-test analysis showed significant improvement in cough severity for both groups and significant improvement in voice severity for the CV group. The VHI-10 scores for the C group did not change significantly. The median number of treatment sessions was 3, with a range of 1-13 sessions. Correlation between changes in severity and number of treatment sessions was not found to be significant at the tested level. CONCLUSIONS: CST represents a unifying approach for treatment of patients with CRC and comorbid voice disorders. CST offered cross-over effects to the voice when subjects were treated for their primary complaint of chronic cough. This treatment of the primary complaint improves function in systems that share a common pathway. LEVEL OF EVIDENCE: 4 Laryngoscope, 131:2747-2751, 2021.

Health Versus Appearance Versus Body Competence: A Content Analysis Investigating Frames of Health Advice in Women's Health Magazines.

The present study investigated the extent to which women's health magazines advise readers to adopt healthy behaviors in order to look good (appearance frame), in order to feel good (health frame), or in order to perform better (body competence frame). A content analysis of 5 years of the 6 highest circulating U.S. women's health magazines revealed a higher frequency of health frames (32.6%) than appearance frames (24.8%) overall, but when beauty/health hybrid magazines (i.e., Shape and Self) were examined separately, appearance frames (32.8%) outnumbered health frames (26.5%). Compared to appearance and health frames, body competence frames were underrepresented (13.3% in the full sample). The visual sexual objectification of female models in women's health magazines was also investigated. Appearance-framed articles (43.2%) were significantly more likely to visually depict women with a high degree of skin exposure than health-framed articles (17.4%), and appearance-framed articles (34.8%) were more likely to focus on individual body parts than health-framed articles (21.3%). In addition, despite the magazines' editorial focus on health, the most frequent category of products advertised was appearance-enhancing products. Results are discussed in light of self-determination theory (Deci & Ryan, 1985) and objectification theory (Fredrickson & Roberts, 1997).

Simultaneous exposure to Escherichia coli heat-labile and heat-stable enterotoxins increases fluid secretion and alters cyclic nucleotide and cytokine production by intestinal epithelial cells.

Enterotoxigenic Escherichia coli (ETEC) is a significant cause of diarrheal disease and death, especially in children in developing countries. ETEC causes disease by colonizing the small intestine and producing heat-labile toxin (LT), heat-stable toxin (ST), or both LT and ST (LT+ST). The majority of ETEC strains produce both ST and LT. Despite the prevalence of LT+ST-producing organisms, few studies have examined the physiologic or immunologic consequences of simultaneous exposure to these two potent enterotoxins. In the current report, we demonstrate that when LT and ST are both present, they increase water movement into the intestinal lumen over and above the levels observed with either toxin alone. As expected, cultured intestinal epithelial cells increased their expression of intracellular cyclic GMP (cGMP) when treated with ST and their expression of intracellular cyclic AMP (cAMP) when treated with LT. When both toxins were present, cGMP levels but not cAMP levels were synergistically elevated compared with the levels of expression caused by the corresponding single-toxin treatment. Our data also demonstrate that the levels of inflammatory cytokines produced by intestinal epithelial cells in response to LT are significantly reduced in animals exposed to both enterotoxins. These findings suggest that there may be complex differences between the epithelial cell intoxication and, potentially, secretory outcomes induced by ETEC strains expressing LT+ST compared with strains that express LT or ST only. Our results also reveal a novel mechanism wherein ST production may reduce the hosts' ability to mount an effective innate or adaptive immune response to infecting organisms.