Cadaver as a first teacher: A module to learn the ethics and values of cadaveric dissection.

OBJECTIVES: The undergraduate medical students must be made aware of the ethical and humanistic values of cadaveric dissection. This study therefore designed, implemented, and evaluated the impact of the module 'Cadaver as a Teacher' (CrAFT) that examines the ethical values of cadaveric dissection. METHODS: This prospective, multimethod study involved 447 first-year undergraduate medical students who had participated in all three sessions of the CrAFT module. Activities included interactive lectures, individual assignments, and a poster-making competition. Students offered a silent tribute and wrote words of gratitude down on a tribute wall. They also expressed their thoughts in the form of essays, poems, and collages. These reflections were qualitatively analysed to generate themes. At the end of the module, an online quiz was conducted to assess the knowledge gained by the students. Their scores were correspondingly recorded and calculated. RESULTS: The major themes identified were: cadaver as a teacher, acknowledgement and thanksgiving, bonding, and empathy. Out of all the test takers, 316 students (94.32%) scored more than a five out of ten. The students strongly felt that the module effectively sensitised them towards the ethical and humanitarian aspects of handling cadavers. CONCLUSIONS: The implementation of an educational module about cadavers is a novel approach towards sensitising medical students. The students believed that sensitising them early on would have helped them establish a practice grounded in professionalism, human values, and empathy.

Identification of a Novel Allosteric Inhibitory Site on Tryptophan Hydroxylase 1 Enabling Unprecedented Selectivity Over all Related Hydroxylases.

Pulmonary arterial hypertension (PAH) has demonstrated multi-serotonin receptor dependent pathologies, characterized by increased tone (5-HT1B receptor) and complex lesions (SERT, 5-HT1B, 5-HT2B receptors) of the pulmonary vasculature together with right ventricular hypertrophy, ischemia and fibrosis (5-HT2B receptor). Selective inhibitors of individual signaling elements - SERT, 5-HT2A, 5HT2B, and combined 5-HT2A/B receptors, have all been tested clinically and failed. Thus, inhibition of tryptophan hydroxylase 1 (TPH1), the rate limiting step in 5-HT synthesis, has been suggested as a more broad, and thereby more effective, mode of 5-HT inhibition. However, selectivity over non-pathogenic enzyme family members, TPH2, phenylalanine hydroxylase, and tyrosine hydroxylase has hampered therapeutic development. Here we describe the site/sequence, biochemical, and biophysical characterization of a novel allosteric site on TPH1 through which selectivity over TPH2 and related aromatic amino acid hydroxylases is achieved. We demonstrate the mechanism of action by which novel compounds selectively inhibit TPH1 using surface plasma resonance and enzyme competition assays with both tryptophan ligand and BH4 co-factor. We demonstrate 15-fold greater potency within a human carcinoid cell line versus the most potent known TPH1/2 non-specific inhibitor. Lastly, we detail a novel canine in vivo system utilized to determine effective biologic inhibition of newly synthesized 5-HT. These findings are the first to demonstrate TPH1-selective inhibition and may pave the way to a truly effective means to reduce pathologic 5-HT and thereby treat complex remodeling diseases such as PAH.

The study of antilingula and its relation to the lingula and mandibular foramen, the presence of mylohyoid bridging in dry mandibles of South Indian population.

BACKGROUND AND OBJECTIVES: The mandibular foramen and the lingula, because of their relation to the inferior alveolar nerve are of clinical significance for the orodental surgeons. Identification of the antilingula is important in mandibular ramus surgery in which the medial surface of the ramus is not visualized. METHODS: The present study includes adult dry 50 mandibles of unknown age and sex. The measurements were taken using vernier calipers. The points taken for measurements were most prominent point on antilingula, tip of lingula, most anterior, posterior and inferior points of mandibular foramen. The measurements were denoted as A, B, C and D which represent the anterior, posterior, superior and inferior distances. RESULTS: Antilingula was present on right side in 25 and on left side in 28 mandibles. There was a significant difference in distances in mean between the antilingula and mandibular foramen of both the sides (p < 0.001). Retromolar foramen was observed in 6 mandibles. Mylohyoid bridging was seen in 3 mandibles. CONCLUSION: The mandibular foramen was located posterosuperior to the antilingula on both the sides. There was no statistical significance in the distances between the lingula and the antilingula. Therefore antilingula can be used as an important surgical landmark for locating the mandibular foramen in mandibular ramus osteotomies.

Discovery, optimization, and biological evaluation of 5-(2-(trifluoromethyl)phenyl)indazoles as a novel class of transient receptor potential A1 (TRPA1) antagonists.

A high throughput screening campaign identified 5-(2-chlorophenyl)indazole compound 4 as an antagonist of the transient receptor potential A1 (TRPA1) ion channel with IC50 = 1.23 µM. Hit to lead medicinal chemistry optimization established the SAR around the indazole ring system, demonstrating that a trifluoromethyl group at the 2-position of the phenyl ring in combination with various substituents at the 6-position of the indazole ring greatly contributed to improvements in vitro activity. Further lead optimization resulted in the identification of compound 31, a potent and selective antagonist of TRPA1 in vitro (IC50 = 0.015 µM), which has moderate oral bioavailability in rodents and demonstrates robust activity in vivo in several rodent models of inflammatory pain.