Empowering the World Through Dentistry

Dentistry is a very specific trade that one develops after years of education and training. With this skill comes a great amount of power and opportunity to serve, and with great skill comes great responsibility. Many dentists have decided to answer the call of third world countries that lack proper health care and specifically dental care. They do this in a variety of ways from sending supplies, supporting a local clinic financially, or traveling to the country for a short-term trip where they provide dental care to as many patients as they are physically able to for 7 to 10 days. In my capstone/thesis experience I propose that instead of practicing the “give a man a fish” philosophy, dentists practice the “teach men to fish” philosophy. This is called the empowerment theory, and it involves the dentist passing on his skills to leaders in a community to address the detrimental issue of improper dental care that is so common in third world countries. I show the theory to be effective through the description of my experiences in Belize, India, and finally Ghana where I participated in a research study with faculty from the University of Kentucky College of Dentistry. Through research of other methods and many hours of experience in other countries, I can prove that dentists following the empowerment theory can make a sustainable impact in the communities they help

Perfluorohexyloctane ophthalmic solution for dry eye disease: pooled analysis of two phase 3 clinical trials

BackgroundDry eye disease (DED) is commonly caused by excessive tear film evaporation due to Meibomian gland dysfunction (MGD). There is a need for DED treatment options that address tear evaporation and benefit patients across a broad range of demographic and disease characteristics. This study evaluated treatment effects of perfluorohexyloctane ophthalmic drop (formerly NOV03) in the pooled dataset from 2 pivotal clinical trials in patients with DED associated with MGD, both in the overall population and in patient subgroups based on sex, age, and baseline severity of eye dryness.MethodsPooled data from 2 similarly designed, phase 3, randomized controlled trials (GOBI, MOJAVE) were analyzed. Patients aged ≥18 years with DED administered perfluorohexyloctane (n=614) or hypotonic (0.6% solution) saline control (n=603) four times daily for 8 weeks. Primary endpoints were total corneal fluorescein staining (tCFS) score (National Eye Institute scale, 0-15) and eye dryness visual analog scale (VAS) score (0-100). Efficacy was evaluated using analysis of covariance among patient subgroups (male and female, older [≥65 years] and younger [18 to <65 years], tCFS score <7 and ≥7, VAS eye dryness score <70 and ≥70, MGD score <7 and ≥7, Schirmer I test <10 mm and ≥10 mm).ResultsReductions in tCFS and VAS eye dryness scores were greater for perfluorohexyloctane versus control. In the overall patient population, least-squares mean treatment difference was −1.1 (95% CI: −1.41 to −0.79; p<0.0001) for tCFS and −9.0 (95% CI: −11.90 to −6.00; p<0.0001) for VAS eye dryness. Treatment favored perfluorohexyloctane over control in all patient subgroup analyses of tCFS and VAS eye dryness. Overall, the most common adverse event with perfluorohexyloctane was blurred vision (2.1% of patients), which was mild and transient.ConclusionsCompared with a hypotonic saline control, perfluorohexyloctane improved both the signs and symptoms of DED, including in patients with greater self-reported severity of eye dryness.Clinical trial registrationThis study represents an integrated analysis of 2 previous clinical trials: GOBI (ClinicalTrials.gov, NCT04139798) and MOJAVE (ClinicalTrials.gov, NCT04567329)

Cystatin A, a Potential Common Link for Mutant Myocilin Causative Glaucoma

Myocilin (MYOC) is a 504 aa secreted glycoprotein induced by stress factors in the trabecular meshwork tissue of the eye, where it was discovered. Mutations in MYOC are linked to glaucoma. The glaucoma phenotype of each of the different MYOC mutation varies, but all of them cause elevated intraocular pressure (IOP). In cells, forty percent of wild-type MYOC is cleaved by calpain II, a cysteine protease. This proteolytic process is inhibited by MYOC mutants. In this study, we investigated the molecular mechanisms by which MYOC mutants cause glaucoma. We constructed adenoviral vectors with variants Q368X, R342K, D380N, K423E, and overexpressed them in human trabecular meshwork cells. We analyzed expression profiles with Affymetrix U133Plus2 GeneChips using wild-type and null viruses as controls. Analysis of trabecular meshwork relevant mechanisms showed that the unfolded protein response (UPR) was the most affected. Search for individual candidate genes revealed that genes that have been historically connected to trabecular meshwork physiology and pathology were altered by the MYOC mutants. Some of those had known MYOC associations (MMP1, PDIA4, CALR, SFPR1) while others did not (EDN1, MGP, IGF1, TAC1). Some, were top-changed in only one mutant (LOXL1, CYP1B1, FBN1), others followed a mutant group pattern. Some of the genes were new (RAB39B, STC1, CXCL12, CSTA). In particular, one selected gene, the cysteine protease inhibitor cystatin A (CSTA), was commonly induced by all mutants and not by the wild-type. Subsequent functional analysis of the selected gene showed that CSTA was able to reduce wild-type MYOC cleavage in primary trabecular meshwork cells while an inactive mutated CSTA was not. These findings provide a new molecular understanding of the mechanisms of MYOC-causative glaucoma and reveal CSTA, a serum biomarker for cancer, as a potential biomarker and drug for the treatment of MYOC-induced glaucoma

Infrared-monitored flash-photolysis of carboxymyoglobin

An infrared-monitored flash-photolysis apparatus capable of measuring absorbance changes to 10\sp{-3}OD over a time range from 10$\mu$s to 10s is described. Measurements made on this apparatus, combined with slower measurements made on a Fourier-transform infrared spectrometer, of the CO-rebinding kinetics of the A\sb0, A\sb1, and A\sb3 conformations of sperm-whale myoglobin (Mb) at atmospheric pressure and neutral pH are reported. The A\sb0, A\sb1, and A\sb3 rebinding kinetics are shown to be non-exponential and parameterized by activation-enthalpy distributions differing in prefactor k\sb0\ (\log(k\sb0/s) = 10.8, 9.3, and 9.8 for the A\sb0, A\sb1, and A\sb3 conformations, respectively) and peak activation-enthalpy H\sb{p}\ (H\sb{p} = 10.4, 9.6, and 17.6 kJ/M, respectively).CO-rebinding kinetics of MbCO ensembles prepared along different paths in the pressure-temperature plane ("freeze" and "squeeze-freeze-release" ensembles) monitored at two frequencies within the A\sb1 band are also reported. No differences between kinetics monitored at 1943.0cm\sp{-1} and 1947.5cm\sp{-1}, and none between the kinetics of the freeze and squeeze-freeze-release ensembles, are resolved. The large uncertainty in the determination of the peak H\sb{p} of the activation-enthalpy distribution (H\sb{p} = 15 (+8,$-$7)kJ/M for the squeeze-freeze-release ensemble monitored at 1943.0cm\sp{-1}) suggests limits of the capability of the apparatus, which are discussed in terms of time resolution.U of I OnlyETDs are only available to UIUC Users without author permissio

Nitric Oxide (NO): An Emerging Target for the Treatment of Glaucoma

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