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

Comparison of Latanoprostene Bunod 0.024% and Timolol Maleate 0.5% in Open-Angle Glaucoma or Ocular Hypertension: The LUNAR Study.

PURPOSE: To compare the intraocular pressure (IOP)-lowering effect of latanoprostene bunod (LBN) 0.024% with timolol maleate 0.5% in subjects with open-angle glaucoma (OAG) or ocular hypertension (OHT). DESIGN: Prospective, randomized, double-masked, parallel-group, noninferiority clinical trial. METHODS: Adults with OAG or OHT from 46 clinical sites (United States and European Union) were randomized 2:1 to LBN instilled once daily (QD) in the evening and vehicle in the morning or timolol instilled twice a day (BID) for 3 months. IOP was measured at week 2, week 6, and month 3 (8 AM, 12 PM, and 4 PM each visit). RESULTS: A total of 387 subjects (LBN, n = 259; timolol, n = 128) completed the study. Analysis of covariance showed that mean IOP reduction with LBN was not only noninferior to timolol but significantly greater (P ≤ .025) than timolol at all but the first time point in this study (week 2, 8 AM). Of LBN- and timolol-treated subjects, respectively, 31.0% and 18.5% (P = .007) had their IOP reduced ≥25% from baseline, and 17.7% and 11.1% (P = .084) had their IOP reduced to ≤18 mm Hg over all time points/visits in this study. Ocular treatment-emergent adverse events, while uncommon, appeared more frequently in the LBN group (all mild-moderate except 1 case of severe hyperemia). CONCLUSIONS: LBN 0.024% QD in the evening was noninferior to timolol 0.5% BID over 3 months of treatment, with significantly greater IOP lowering in subjects with OAG or OHT at all but the earliest time point evaluated, and demonstrated a good safety profile

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

Evaluation of the Effect of Latanoprostene Bunod Ophthalmic Solution, 0.024% in Lowering Intraocular Pressure over 24 h in Healthy Japanese Subjects

Introduction: Latanoprostene bunod is a novel nitric oxide (NO)-donating prostaglandin F2α receptor agonist in clinical development for the reduction of intraocular pressure (IOP) in patients with open-angle glaucoma or ocular hypertension. We evaluated the effect of latanoprostene bunod 0.024% instilled once daily (QD) on lowering IOP over a 24-h period in healthy Japanese subjects following 14 days of treatment. Methods: This was a single-arm, single-center, open-label clinical study of 24 healthy Japanese male volunteers. A baseline IOP profile was established in both eyes in the sitting position at 8 PM, 10 PM, 12 AM, 2 AM, 4 AM, 8 AM, 10 AM, 12 PM, and 4 PM using a Goldmann applanation tonometer. Subjects subsequently instilled latanoprostene bunod 0.024% QD at 8 PM for 14 days in both eyes. The absolute and change from baseline in sitting IOP was assessed on day 14. Results: The mean (SD) age of the subjects was 26.8 (6.3) years, and mean (SD) baseline IOP was 13.6 (1.3) mmHg in the study eye. Latanoprostene bunod 0.024% instilled QD for 14 days reduced IOP at all the evaluated time points (P < 0.001) with a mean (SD) 24-h reduction of 3.6 (0.8) mmHg or 27% from the baseline in the study eye. Peak and trough IOP lowering occurred at 8 AM and 8 PM (12 and 24 h following instillation) with a mean reduction of 4.2 (1.8) mmHg, or 30%, and 2.8 (2.2) mmHg, or 20%, respectively. Punctate keratitis and ocular hyperemia, both mild in severity, were the most common adverse events. Conclusion: Latanoprostene bunod ophthalmic solution 0.024%, dosed QD for 14 days, significantly lowered mean IOP in healthy Japanese subjects during the entire 24-h period. Studies of latanoprostene bunod in patients diagnosed with normal tension glaucoma are warranted. Trial Registration: Clinicaltrials.gov identifier NCT01895985. Funding: Bausch & Lomb, Inc

Latanoprostene Bunod 0.024% versus Timolol Maleate 0.5% in Subjects with Open-Angle Glaucoma or Ocular Hypertension: The APOLLO Study.

PurposeTo compare the diurnal intraocular pressure (IOP)-lowering effect of latanoprostene bunod (LBN) ophthalmic solution 0.024% every evening (qpm) with timolol maleate 0.5% twice daily (BID) in subjects with open-angle glaucoma (OAG) or ocular hypertension (OHT).DesignPhase 3, randomized, controlled, multicenter, double-masked, parallel-group clinical study.ParticipantsSubjects aged ≥18 years with a diagnosis of OAG or OHT in 1 or both eyes.MethodsSubjects were randomized (2:1) to a 3-month regimen of LBN 0.024% qpm or timolol 0.5% 1 drop BID. Intraocular pressure was measured at 8 am, 12 pm, and 4 pm of each postrandomization visit (week 2, week 6, and month 3). Adverse events were recorded throughout the study.Main outcome measuresThe primary efficacy end point was IOP in the study eye measured at each of the 9 assessment time points. Secondary efficacy end points included the proportion of subjects with IOP ≤18 mmHg consistently at all 9 time points and the proportion of subjects with IOP reduction ≥25% consistently at all 9 time points.ResultsOf 420 subjects randomized, 387 completed the study (LBN 0.024%, n = 264; timolol 0.5%, n = 123). At all 9 time points, the mean IOP in the study eye was significantly lower in the LBN 0.024% group than in the timolol 0.5% group (P ≤ 0.002). At all 9 time points, the percentage of subjects with mean IOP ≤18 mmHg and the percentage with IOP reduction ≥25% were significantly higher in the LBN 0.024% group versus the timolol 0.5% group (mean IOP ≤18 mmHg: 22.9% vs. 11.3%, P = 0.005; IOP reduction ≥25%: 34.9% vs. 19.5%, P = 0.001). Adverse events were similar in both treatment groups.ConclusionsIn this phase 3 study, LBN 0.024% qpm demonstrated significantly greater IOP lowering than timolol 0.5% BID throughout the day over 3 months of treatment. Latanoprostene bunod 0.024% was effective and safe in these adults with OAG or OHT

Latanoprostene Bunod 0.024% versus Timolol Maleate 0.5% in Subjects with Open-Angle Glaucoma or Ocular Hypertension: The APOLLO Study.

PurposeTo compare the diurnal intraocular pressure (IOP)-lowering effect of latanoprostene bunod (LBN) ophthalmic solution 0.024% every evening (qpm) with timolol maleate 0.5% twice daily (BID) in subjects with open-angle glaucoma (OAG) or ocular hypertension (OHT).DesignPhase 3, randomized, controlled, multicenter, double-masked, parallel-group clinical study.ParticipantsSubjects aged ≥18 years with a diagnosis of OAG or OHT in 1 or both eyes.MethodsSubjects were randomized (2:1) to a 3-month regimen of LBN 0.024% qpm or timolol 0.5% 1 drop BID. Intraocular pressure was measured at 8 am, 12 pm, and 4 pm of each postrandomization visit (week 2, week 6, and month 3). Adverse events were recorded throughout the study.Main outcome measuresThe primary efficacy end point was IOP in the study eye measured at each of the 9 assessment time points. Secondary efficacy end points included the proportion of subjects with IOP ≤18 mmHg consistently at all 9 time points and the proportion of subjects with IOP reduction ≥25% consistently at all 9 time points.ResultsOf 420 subjects randomized, 387 completed the study (LBN 0.024%, n = 264; timolol 0.5%, n = 123). At all 9 time points, the mean IOP in the study eye was significantly lower in the LBN 0.024% group than in the timolol 0.5% group (P ≤ 0.002). At all 9 time points, the percentage of subjects with mean IOP ≤18 mmHg and the percentage with IOP reduction ≥25% were significantly higher in the LBN 0.024% group versus the timolol 0.5% group (mean IOP ≤18 mmHg: 22.9% vs. 11.3%, P = 0.005; IOP reduction ≥25%: 34.9% vs. 19.5%, P = 0.001). Adverse events were similar in both treatment groups.ConclusionsIn this phase 3 study, LBN 0.024% qpm demonstrated significantly greater IOP lowering than timolol 0.5% BID throughout the day over 3 months of treatment. Latanoprostene bunod 0.024% was effective and safe in these adults with OAG or OHT