Inducible desensitization to capsaicin with repeated low-dose exposure in human volunteers.

Responses to capsaicin are reduced following repeated exposure, a phenomenon known as capsaicin desensitization. Heavy consumers of chilies consistently report reduced oral burn relative to infrequent consumers, presumably due to chronic desensitization. However, the mechanism(s) underlying capsaicin desensitization remain poorly understood. We hypothesized that reduced response to capsaicin due to repeated oral exposure may result from a change in the expression of the capsaicin receptor (TRPV1) gene. To test this, we conducted two longitudinal desensitization studies in healthy human volunteers. In Study 1, 51 adults completed a 17-day capsaicin desensitization protocol. The study consisted of three in-person visits where they were asked to sample stimuli, including 3, 6, and 9 ppm capsaicin, and rate intensity on a general labeled magnitude scale (gLMS). Between days 3 & 17, participants rinsed at home with 6 ppm capsaicin (n = 31) or a control (n = 20) solution (20 uM sucrose octaccetate; SOA) twice a day. Before and after the oral exposure protocol, a clinician collected fungiform papillae. Participants randomized to the capsaicin rinse showed a statistically significant reduction in oral burn ratings that was not observed in controls, indicating repeated low-dose exposure can systematically induce desensitization. TRPV1 expression was not associated with reported capsaicin burn, and there was no evidence of a decrease in TRPV1 expression following capsaicin exposure. In Study 2, participants (n = 45) rinsed with 6 ppm capsaicin in a similar protocol, rating capsaicin, vanillyl butyl ether (VBE), cinnamaldehyde, ethanol, menthol, and sucrose on days 1, 3, & 17. Burn from capsaicin, VBE, cinnamaldehyde, and ethanol all showed a statistically significant change - capsaicin, VBE and cinnamaldehyde burn all dropped ∼20 %, and a larger reduction was seen for ethanol - while menthol cooling and sucrose sweetness did not change. Collectively, this suggests reductions in oral burn following chronic capsaicin exposure generalizes to other stimuli (i.e., cross desensitization) and this cannot be explained by a change in TRPV1 mRNA expression. More work is needed to elucidate the underlying mechanism for capsaicin desensitization in the oral cavity.

John Greenwood's sidenotes on a 1778 John Hunter text at The New York Academy of Medicine.

John Greenwood (1760-1819) was George Washington's preferred dentist. He practiced in New York and made at least one of eight sets of dentures Washington wore (currently in the collection of the New York Academy of Medicine (NYAM). We know very little about John Greenwood's (JG) formal education, except that he came from a famous family of dentists. He inherited from his father, Isaac Greenwood, one important book of the time, John Hunter's 1778 treatise, A Natural History of the Human Teeth. That copy was donated to the New York Academy of Medicine by descendants of John Greenwood. Recently, we became aware of extensive marginalia that John Greenwood wrote in this book. The present article describes John Greenwood's opinion on a variety of dental subjects such as the causes and mechanisms of tooth destruction and gum disease and the presence of microscopic annamalcula that were thought to be connected to poor oral hygiene. Although John Greenwood was self-educated, his observations are surprisingly insightful and at least 37 years ahead of what was described in the contemporary literature.

The Changing Scene of Practicing Dentistry: A Survey of the Past 200 Years.

If one could be a patient repeatedly, every twenty-five years, starting in 1825, the evolution and comparison of dental care and dental practice would be historically meaningful. Such a time travel, as a perpetual patient through 200 years, is the purpose of this paper. The changes that occurred over 200 years provide a sense of the progress in treating patients and the transformation of a painful and dreaded experience to a highly sophisticated painless profession.

The Life of a Dental Student: Educational and Social Changes from 1880 to 2020.

If one could attend the same College of Dentistry repeatedly, every twenty years, starting in 1880, the evolution and comparison of student life would be historically meaningful. Such a time travel, as a perpetual dental student through 140 years, is the purpose of this paper. To illustrate this unique perspective, New York College of Dentistry, was chosen. This large East-Coast private school has been in existence since 1865, and reflects the typical dental educational environment at that time. The changes that occurred over 140 years, however, may or may not be typical of most private dental schools in the United States due to a multiplicity of factors. Likewise, the life of a dental student has changed over the past 140 years, as dental education, oral care, and dental practice have significantly evolved.

A Model for Teaching History of Dentistry and Medicine to Dental Students - The NYU Experience.

Teaching History of Dentistry and Medicine in dental curricula has declined over the past half century. The cause of this decline is a lack of expertise, time in a crowded curriculum and a decline in interest in the humanities among dental students. The current paper describes a model of teaching History of Dentistry and Medicine at New York University College of Dentistry, a model that could be replicated at other schools.

Reprogramming cultured human fungiform (HBO) taste cells into neuron-like cells through in vitro induction.

Human taste cells are a heterogeneous population of specialized epithelial cells that are constantly generated from progenitor taste cells. Type I and type III taste cells express some neural markers, and studies have reported that direct innervation by neurons is not required for taste cell development. To our knowledge, no previous study has demonstrated that taste cells can differentiate into neuron-like cells or any other non-taste cell type. Here, for the first time, we describe a simple in vitro method that uses a serum-free neural induction medium to differentiate cultured physiologically functional primary human taste (HBO) cells into neuron-like cells in 2-3 wk with high efficiency. We verified neural attributes of these HBO-derived neuron-like with immunocytochemistry, single-cell calcium imaging, and DiI staining and examined cell morphology using transmission electron microscopy. Induced neuron-like cells demonstrated neuron-specific proteins, dendritic and axonal morphology, and networking behaviors. This technique will open new avenues for translational medicine, autologous cell therapy, regenerative medicine, therapy for neurodegenerative disorders, and drug screening.

Chemosensory loss in COVID-19.

The COVID-19 pandemic caused by SARS-CoV-2 virus quickly spread globally, infecting over half a billion individuals, and killing over 6 million*. One of the more unusual symptoms was patients' complaints of sudden loss of smell and/or taste, a symptom that has become more apparent as the virus mutated into different variants. Anosmia and ageusia, the loss of smell and taste, respectively, seem to be transient for some individuals, but for others persists even after recovery from the infection. Causes for COVID-19-associated chemosensory loss have undergone several hypotheses. These include non-functional or destroyed olfactory neurons and gustatory receptors or of their supporting cells, disruption of the signaling protein Neuropilin-1, and disruption in the interaction with semaphorins, key molecules in the gustatory and olfactory axon guidance. The current paper will review these hypotheses and chart out potential therapeutic avenues.

Teaching History of Dentistry in Dental Curricula A survey of 393 dental schools in 100 countries.

Teaching history of dentistry and/or medicine in dental schools is not a priority today. A half a century ago it was part of a significant number of dental school curricula. As advances in science occurred and more demand on the curriculum were made, history of medicine and dentistry (HMD) was largely cast aside. In a recent survey of 393 dental programs in 100 countries on five continents, only 18.8% have a stand-alone course in HMD. Nearly half of the programs though have at least 1-2 hours of curriculum time devoted to HMD. When we consider a subset of the above survey, only 5% of dental schools in the US and Canada have a stand-alone course. The exclusion of HMD from current dental curricula is shortsighted. Teaching only current and state-of-the art aspects of dentistry is like showing a still image from the end of a movie without watching the rest.

Electricity.

Quackery in medicine is as old as medicine. In times of crisis desperate patients believe in extraordinary claims. In the annals of pain killer quack medicine, elixirs, nostrums and liniments hold a special position. The College of Dentistry at NYU received a collection of 234 bottles of quack medicine dating from approximately 1850 through 1940.In this paper, the THIRD in a series of articles featuring "Elixirs of the Past", we focus on five particularly notable samples claiming to have "electric" properties: Electric Brand Oil Compound, Hunt's Lightening Oil, Electric Indian Liniment, Regent's Electric Liniment and Haven's Electro-magnetic Liniment. Needless to say, none of these contained electricity or even electrolytes for that matter. In 1906, Congress enacted The Pure Food and Drug Act to prohibit exaggerated or unsubstantiated claims in the marketing and labeling of household products and to control the use of potentially harmful ingredients. The modern-day use of internet advertisements to make unsupported claims is in some ways even more brazen than the advertisements from a century ago.

Opium.

Quackery in medicine is as old as medicine itself. In times of crisis, desperate patients often believe extraordinary claims. In the annals of pain-killer quack medicine, elixirs, nostrums and liniments hold a prominent position. NYU College of Dentistry (NYUCD) has a collection of 234 bottles of such medicines dating from the mid-1800s through 1940. This paper is the second in a series of articles featuring "Elixirs of the Past" in which we bring to light five more samples containing opium: Dr. B.J. Kendall's Instant Relief for Pain, Dr. Munn's Elixir of Opium, Dill's Balm of Life, Foley's Pain Relief, and Brown's Instant Relief for Pain. These are just five examples out of countless syrups, nostrums, balm or liniments that contained narcotics and were linked to overdose, addiction and sometimes death. In 1906, Congress enacted The Pure Food and Drug Act to stop unsubstantiated medicinal claims and control the use of addictive substances. The modern-day use of internet advertisements to make unsupported claims is in some ways even more brazen than the advertisements from a century ago. Indeed, the recent widespread use of prescription painkillers, along with the resulting epidemic in opiate addiction that has caused upwards of 50,000 deaths is a case in point.

Pandemics and education: A historical review.

Major pandemics have tremendous effects on society. They precipitated the early decline of the Western Roman Empire and helped spread Christianity. There are countless such examples of infectious diseases altering the course of history. The impact of epidemics on education however is less well documented. This present historical account of the past 800 years looks specifically at how some aspects of education were shaped from the early medieval epidemics such as leprosy and the Black Plague to the Spanish Flu and COVID-19. Leprosy changed religious education, and the Black Plague may have contributed to the rise of medical schools, hospitals, public health education, and led to the implementation of lazarettos and the quarantine. The smallpox epidemic helped usher in public health education for immunization, while the 1918 Spanish Flu precipitated the rise of education by correspondence, and recently COVID-19 has catapulted remote digital learning to the forefront of higher education.

Magnetism.

Quackery in medicine is as old as medicine itself. In times of crisis desperate patients often believe extraordinary claims. In the annals of pain killer quack medicine, elixirs, nostrums and liniments hold a special position. The College of Dentistry at NYU received a collection of 234 bottles of nostrums and liniments dating from approximately 1850 through 1940. In this paper, the FOURTH in a series of articles featuring "Elixirs of the Past" we bring to light four more samples claiming to have magnetic properties: Dr. J.R. Miller's Magnetic Balm, Havens' Electromagnetic Liniment, Headman's Magnetic Liniments, and Magnetic Cream. It goes without saying that none of these had any magnetic properties. In 1906, Congress enacted The Pure Food and Drug Act to prohibit exaggerated or unsubstantiated claims in the marketing and labeling of household products and to control the use of potentially harmful ingredients. The modern-day use of internet advertisements to make unsupported claims is in some ways even more brazen than the advertisements from a century ago.

Snake Oil and Indian Liniment.

Quackery in medicine is as old as medicine itself. In times of crisis, desperate patients often believe extraordinary claims. In the annals of pain-killer quack medicine, snake oil, elixirs, nostrums and Indian liniments hold a special position. NYU College of Dentistry (NYUCD) has a collection of 234 bottles of such medicines dating from the mid-1800s through 1940. This paper is the fifth in a series of articles featuring "Elixirs of the Past" in which we bring to light six more samples with claims to traditional Chinese or American Indian medicine using snake oil: Virex Compound, Rattlesnake Bill's Oil, Electric Indian Liniment, The King of All Indian Oils, Millerhaus Antiseptic Oil and Celebrated Indian Lotion. The six examples are just a few quack medications linked to fraud, overdose, addiction or death. In 1906, Congress enacted The Pure Food and Drug Act and reinforced it with the Federal Food, Drug and Cosmetic Act of 1938, to stop unsubstantiated medicinal claims and control the use of addictive and dangerous substances. The modern-day use of social media to advertise quack medicine is in some ways even more brazen than selling patent medicine a century ago.

Zika virus infection in chemosensory cells.

Zika virus (ZIKV) is an emerging virus belonging to the genus Flavivirus. ZIKV infection is a significant health concern, with increasing numbers of reports of microcephaly cases in fetuses and Guillain-Barré syndrome (GBS) in adults. Interestingly, chemosensory disturbances are also reported as one of the manifestations of GBS. ZIKV infects several human tissues and cell types in vitro and in vivo. However, there is no study demonstrating ZIKV infection and replication in chemosensory cells, including olfactory and taste cells. Taste papilla and olfactory cells are chemosensory receptor cells with unique histological, molecular, and physiological characteristics. Here we examined ZIKV infection (PRVABC59) in cultured human olfactory epithelial cells (hOECs) and fungiform taste papilla (HBO) cells in vitro, as well as in vivo mouse taste and olfactory epithelial and olfactory bulb tissues. Interestingly, while HBO cells showed resistance to ZIKV replication, hOECs were highly susceptible for ZIKV infection and replication. Further, we demonstrated the presence of ZIKV particles and expression of viral proteins in olfactory epithelium, as well as in olfactory bulb, but not in taste papillae, of immunocompromised mice (ifnar/-) infected with the PRVABC59 strain of ZIKV. These observations suggest that chemosensory cells in the olfactory neuroepithelium and olfactory bulb may be important tissues for ZIKV replication and dissemination.

The College of Dentistry at New York University Brings this Section to Life with "Elixers of the Past".

Quackery in medicine is as old as medicine. In times of crisis desperate patients believe in extraordinary claims. In the annals of pain killer quack medicine, elixirs, nostrums and liniments hold a preeminent position. The College of Dentistry at NYU received a collection of 237 bottles of nostrums and liniments dating from approximately 1850 through 1940. In this paper we inaugurate a series of articles featuring "Elixirs of the Past". We start this series with four samples, Mrs. Winslow's Soothing Syrup, Dr. Grove's Anodyne for Infants, Jadway's Elixir for Infants and Kopp's, four of many teething syrups that contained narcotics and were linked to infant death at the end of the 19th century. In 1906 Congress introduced The Pure Food and Drug Act to stop unsubstantiated claims. Companies were fined in court cases and finally compelled to remove narcotics and stop making unsubstantiated claims. Unmasking past claims hopefully stops quacks of today. Nevertheless, far more unfounded and extraordinary claims are being made today, using social media, perhaps more brazenly than one hundred years ago.

The Teaching of Personalized Dentistry in North American Dental Schools: Changes from 2014 to 2017.

The aim of this study was to assess the development of personalized dentistry in the curricula of North American dental schools from 2014 to 2017. In 2014, a web-based survey on personalized medicine/dentistry (PM/PD) was distributed to academic deans of all U.S. (n=65) and Canadian (n=10) dental schools with graduating classes. The results (n=42; 56% response rate) showed that few schools had plans for implementation of PM/PD at the time, even though the majority of respondents reported feeling that PM/PD should be taught in the curriculum and will impact clinical practice in the future. A three-year followup survey in 2017, sent to the same 75 schools, was designed to reassess the teaching/practice of PM/PD in dental schools in both didactic and clinical curricula. In the results of the 2017 survey (n=30; 40% response rate), the majority of respondents reported feeling that PM/PD should be taught in dental curricula. However, while most respondents indicated their schools did not teach PM/PD as a portion of their didactic curricula, they reported that specific pertinent PM/PD topics were taught as part of other courses in their curricula. The 2017 survey also evaluated the use of seven genetics-based and eight non-genetics-based PM/PD diagnostics in the schools' clinical curricula. Overall, non-genetics-based diagnostics were used more often than genetics-based diagnostics, and the use of genetics-based diagnostics was more prevalent in postgraduate than predoctoral clinics. Personalized dentistry will inevitably be part of the dental professional's future and should be reflected in basic science research, clinical settings, and dental school curricula in both predoctoral and postgraduate programs.

Mammalian Taste Cells Express Functional Olfactory Receptors.

The peripheral taste and olfactory systems in mammals are separate and independent sensory systems. In the current model of chemosensation, gustatory, and olfactory receptors are genetically divergent families expressed in anatomically distinct locations that project to disparate downstream targets. Although information from the 2 sensory systems merges to form the perception of flavor, the first cross talk is thought to occur centrally, in the insular cortex. Recent studies have shown that gustatory and olfactory receptors are expressed throughout the body and serve as chemical sensors in multiple tissues. Olfactory receptor cDNA has been detected in the tongue, yet the presence of physiologically functional olfactory receptors in taste cells has not yet been demonstrated. Here we report that olfactory receptors are functionally expressed in taste papillae. We found expression of olfactory receptors in the taste papillae of green fluorescent protein-expressing transgenic mice and, using immunocytochemistry and real-time quantitative polymerase chain reaction experiments, the presence of olfactory signal transduction molecules and olfactory receptors in cultured human fungiform taste papilla (HBO) cells. Both HBO cells and mouse taste papilla cells responded to odorants. Knockdown of adenylyl cyclase mRNA by specific small inhibitory RNA and pharmacological block of adenylyl cyclase eliminated these responses, leading us to hypothesize that the gustatory system may receive olfactory information in the periphery. These results provide the first direct evidence of the presence of functional olfactory receptors in mammalian taste cells. Our results also demonstrate that the initial integration of gustatory and olfactory information may occur as early as the taste receptor cells.

Tissue-Dependent Expression of Bitter Receptor TAS2R38 mRNA.

TAS2R38 is a human bitter receptor gene with a common but inactive allele; people homozygous for the inactive form cannot perceive low concentrations of certain bitter compounds. The frequency of the inactive and active forms of this receptor is nearly equal in many human populations, and heterozygotes with 1 copy of the active form and 1 copy of the inactive form have the most common diplotype. However, even though they have the same genotype, heterozygotes differ markedly in their perception of bitterness, perhaps in part because of differences in TAS2R38 mRNA expression. Other tissues express this receptor too, including the nasal sinuses, where it contributes to pathogen defense. We, therefore, wondered whether heterozygous people had a similar wide range of TAS2R38 mRNA in sinonasal tissue and whether those with higher TAS2R38 mRNA expression in taste tissue were similarly high expressers in nasal tissue. To that end, we measured gene expression by quantitative PCR in taste and sinonasal tissue and found that expression abundance in one tissue was not related to the other. We confirmed the independence of expression in other tissue pairs expressing TAS2R38 mRNA, such as pancreas and small intestine, using autopsy data from the Genotype-Tissue Expression project (although people with high expression of TAS2R38 mRNA in colon also tended to have higher expression in the small intestine). Thus, taste tissue TAS2R38 mRNA expression among heterozygotes is unlikely to predict expression in other tissues, perhaps reflecting tissue-dependent function, and hence regulation, of this protein.

Nicotinic acetylcholine receptor (CHRN) expression and function in cultured human adult fungiform (HBO) taste cells.

In rodents, CHRNs are involved in bitter taste transduction of nicotine and ethanol. Currently, it is not clear if CHRNs are expressed in human taste cells and if they play a role in transducing the bitter taste of nicotine and ethanol or in the synthesis and release of neurohumoral peptides. Accordingly, we investigated the expression and functional role of CHRNs in HBO cells. Using molecular techniques, we demonstrate that a subset of HBO cells express CHRNs that also co-express TRPM5, T1R3 or T2R38. Exposing HBO cells to nicotine or ethanol acutely or to nicotine chronically induced a differential increase in the expression of CHRN mRNA and protein in a dose- and time-dependent manner. Acutely exposing HBO cells to a mixture containing nicotine plus ethanol induced a smaller increase in CHRN mRNAs relative to nicotine or ethanol treatment alone. A subset of HBO cells responded to nicotine, acetylcholine and ATP with a transient increase in [Ca2+]i. Nicotine effects on [Ca2+]i were mecamylamine sensitive. Brain-derived neurotrophic factor (BDNF) protein was detected in HBO cells using ELISA. Acute nicotine exposure decreased BDNF in HBO cells and increased BDNF release in the medium. CHRNs were also detected in HEK293 cells by RT-PCR. Unlike HBO cells, CHRNs were localized in most of HEK293 cells and majority of HEK293 cells responded to nicotine and ethanol stimulation with a transient increase in [Ca2+]i. BDNF levels in HEK293 cells were significantly higher than in HBO cells but the nicotine induced release of BDNF in the media was a fraction of the BDNF cellular content. We conclude that CHRNs are expressed in TRPM5 positive HBO cells. CHRN mRNA expression is modulated by exposure to nicotine and ethanol in a dose- and time-dependent manner. Nicotine induces the synthesis and release of BDNF in HBO cells.