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1.  Inflammatory Biomarkers and Progression of Diabetic Retinopathy in African Americans With Type 1 Diabetes 
We examined whether baseline plasma levels of markers of inflammation and endothelial dysfunction are associated with the incidence of diabetic retinopathy (DR) in African Americans with type 1 insulin-dependent diabetes mellitus (T1DM).
At baseline and follow-up examinations, detailed ocular examination, structured clinical interview, venous blood specimens, and masked grading of seven standard field retinal photographs were obtained. Baseline plasma levels of 28 inflammatory biomarkers, measured using multiplex bead analysis system, were measured in the participants.
After adjusting for age, glycemic control, and other potential confounders, baseline plasma levels of E-selectin were associated significantly with progression of DR, E-selectin and tumor necrosis factor-α (TNF-α) levels with incidence of proliferative DR (PDR), and soluble intercellular adhesion molecule-1 (sICAM-1) and TNF-α levels with incidence of macular edema (ME).
In African Americans with T1DM, inflammation and endothelial dysfunction precede the development of DR, thus supporting the notion that inflammation may influence progression/incidence of disease.
In 412 African Americans with type 1 diabetes baseline plasma levels of the adhesion molecules E selectin and s-ICAM1, and of the proinflammatory cytokine TNF-α were found to be independent predictors of diabetic retinopathy progression.
PMCID: PMC3743457  PMID: 23847308
inflammation; diabetic retinopathy; African Americans; incidence; biomarkers
2.  The Effect of Brain-Derived Neurotrophic Factor on Periodontal Furcation Defects 
PLoS ONE  2014;9(1):e84845.
This study aimed to observe the regenerative effect of brain-derived neurotrophic factor (BDNF) in a non-human primate furcation defect model. Class II furcation defects were created in the first and second molars of 8 non-human primates to simulate a clinical situation. The defect was filled with either, Group A: BDNF (500 µg/ml) in high-molecular weight-hyaluronic acid (HMW-HA), Group B: BDNF (50 µg/ml) in HMW-HA, Group C: HMW-HA acid only, Group D: empty defect, or Group E: BDNF (500 µg/ml) in saline. The healing status for all groups was observed at different time-points with micro computed tomography. The animals were euthanized after 11 weeks, and the tooth-bone specimens were subjected to histologic processing. The results showed that all groups seemed to successfully regenerate the alveolar buccal bone, however, only Group A regenerated the entire periodontal tissue, i.e., alveolar bone, cementum and periodontal ligament. It is suggested that the use of BDNF in combination with a scaffold such as the hyaluronic acid in periodontal furcation defects may be an effective treatment option.
PMCID: PMC3891769  PMID: 24454754
3.  The Effect of Simplifying Dental Implant Drilling Sequence on Osseointegration: An Experimental Study in Dogs 
Objectives. To test the hypothesis that there would be no differences in osseointegration by reducing the number of drills for site preparation relative to conventional drilling sequence. Methods. Seventy-two implants were bilaterally placed in the tibia of 18 beagle dogs and remained for 1, 3, and 5 weeks. Thirty-six implants were 3.75 mm in diameter and the other 36 were 4.2 mm. Half of the implants of each diameter were placed under a simplified technique (pilot drill + final diameter drill) and the other half were placed under conventional drilling where multiple drills of increasing diameter were utilized. After euthanisation, the bone-implant samples were processed and referred to histological analysis. Bone-to-implant contact (BIC) and bone-area-fraction occupancy (BAFO) were assessed. Statistical analyses were performed by GLM ANOVA at 95% level of significance considering implant diameter, time in vivo, and drilling procedure as independent variables and BIC and BAFO as the dependent variables. Results. Both techniques led to implant integration. No differences in BIC and BAFO were observed between drilling procedures as time elapsed in vivo. Conclusions. The simplified drilling protocol presented comparable osseointegration outcomes to the conventional protocol, which proved the initial hypothesis.
PMCID: PMC3572684  PMID: 23431303
4.  Nanomechanical Characterization of Canine Femur Bone for Strain Rate Sensitivity in the Quasistatic Range under Dry versus Wet Conditions 
As a strain rate-dependent material, bone has a different mechanical response to various loads. Our aim was to evaluate the effect of water and different loading/unloading rates on the nanomechanical properties of canine femur cortical bone. Six cross-sections were cut from the diaphysis of six dog femurs and were nanoindented in their cortical area. Both dry and wet conditions were taken into account for three quasistatic trapezoid profiles with a maximum force of 2000 μN (holding time = 30 s) at loading/unloading rates of 10, 100, and 1000 μN/s, respectively. For each specimen, 254 ± 9 (mean ± SD) indentations were performed under different loading conditions. Significant differences were found for the elastic modulus and hardness between wet and dry conditions (P < 0.001). No influence of the loading/unloading rates was observed between groups except for the elastic modulus measured at 1000 μN/s rate under dry conditions (P < 0.001) and for the hardness measured at a rate of 10 μN/s under wet conditions (P < 0.001). Therefore, for a quasistatic test with peak load of 2000 μN held for 30 s, it is recommended to nanoindent under wet conditions at a loading/unloading rate of 100–1000 μN/s, so the reduced creep effect allows for a more accurate computation of mechanical properties.
PMCID: PMC3540738  PMID: 23365577
5.  Safety and efficacy of vagus nerve stimulation in Fibromyalgia: A Phase I/II proof of concept trial 
Pain medicine (Malden, Mass.)  2011;12(9):1406-1413.
We performed an open label Phase I/II trial to evaluate the safety and tolerability of vagus nerve stimulation (VNS) in patients with treatment-resistant fibromyalgia (FM) as well as to determine preliminary measures of efficacy in these patients.
Of 14 patients implanted with the VNS stimulator, 12 completed the initial 3 month study of VNS; 11 returned for follow-up visits 5, 8 and 11 months after start of stimulation. Therapeutic efficacy was assessed with a composite measure requiring improvement in pain, overall wellness, and physical function. Loss of both pain and tenderness criteria for the diagnosis of FM was added as a secondary outcome measure because of results found at the end of 3 months of stimulation.
Side effects were similar to those reported in patients treated with VNS for epilepsy or depression and, in addition, dry mouth and fatigue were reported. Two patients did not tolerate stimulation. At 3 months, five participants had attained efficacy criteria; of these, two no longer met widespread pain or tenderness criteria for the diagnosis of FM. The therapeutic effect seemed to increase over time in that additional participants attained both criteria at 11 months.
Side effects and tolerability were similar to those found in disorders currently treated with VNS. Preliminary outcome measures suggested that VNS may be a useful adjunct treatment for FM patients resistant to conventional therapeutic management but further research is required to better understand its actual role in the treatment of FM.
PMCID: PMC3173600  PMID: 21812908
6.  Medical and Psychological Risk Factors for Incident Hypertension in Type 1 Diabetic African-Americans 
Objective. To determine risk factors for the development of hypertension among African-Americans living with type 1 diabetes. Methods. African-Americans with type 1 diabetes (n = 483) participated in a 6-year followup. At both baseline and followup blood pressure was measured twice in both sitting and standing positions using a standard protocol. Patients had a structured clinical interview, ocular examination, retinal photographs, and blood and urine assays and completed the Hostility and Direction of Hostility Questionnaire (HDHQ) and the Beck Depression Inventory (BDI). Results. Of the 280 diabetic patients with no hypertension at baseline, 82 (29.3%) subsequently developed hypertension over the 6-year followup. Baseline older age, longer duration of diabetes, family history of hypertension, greater mean arterial blood pressure, overt proteinuria, increasing retinopathy severity, peripheral neuropathy, smoking, and higher hostility scores were significantly associated with the development of hypertension. Multivariate analyses showed that higher hostility scores and overt proteinuria were significantly and independently associated with the development of hypertension in this population. Conclusions. The development of hypertension in African-Americans living with type 1 diabetes appears to be multifactorial and includes both medical (overt proteinuria) as well as psychological (high hostility) risk factors.
PMCID: PMC3163036  PMID: 21876788
7.  Sex Differences in Plasma Prolactin Response to Tryptophan in Chronic Fatigue Syndrome Patients With and Without Comorbid Fibromyalgia 
Journal of Women's Health  2010;19(5):951-958.
Some think chronic fatigue syndrome (CFS) and fibromyalgia (FM) are variants of the same illness process. This would imply that CFS patients with and without comorbid FM have similar biological underpinnings. To test this, we compared serotonergic-based responses, plasma prolactin (PRL), and self-reported measures of fatigue to intravenous infusion of tryptophan among patients with CFS alone, CFS + FM, and healthy controls.
Men and women with CFS alone or CFS + FM and healthy subjects, none with current major depressive disorder (MDD), were given 120 mg of l-tryptophan per kg lean body mass intravenously (i.v.). Before and after tryptophan infusion, blood samples were collected, and plasma PRL, tryptophan, and kynurenine concentrations were determined.
Women with CFS alone, but not CFS + FM, showed upregulated plasma PRL responses compared with controls. There were no differences among groups of men. Plasma tryptophan and kynurenine concentrations did not differ among groups.
These results indicate that women with CFS alone have upregulated serotonergic tone that is not seen in those with comorbid FM. The lack of effect in men suggests a mechanism that might explain, in part, the increased prevalence of CFS in women. The data support the interpretation that CFS in women is a different illness from FM.
PMCID: PMC2875960  PMID: 20384451
8.  Clinically-Relevant Design Features of a Three-Dimensional Correct Molar Crown and Related Maximum Principal Stress. A Finite Element Model Study 
To evaluate the effects of clinically relevant variables on the maximum principal stress (MPS) in the veneer layer of an anatomically correct veneer-core-cement-tooth model.
The average dimensions of a mandibular first molar crown were imported into CAD software; a tooth preparation was modeled by reducing the proximal walls by 1.5 mm and the occlusal surface by 2.0 mm. ‘Crown systems’ were composed by varying characteristics of a cement layer, structural core, and veneer solid, all designed to fit the tooth preparation. The main and interacting effects of proximal wall height reduction, core material, core thickness, cement modulus, cement thickness, and load position on the maximum stress distribution were derived from a series of nite element models and analyzed in a factorial analysis of variance.
The average MPS in the veneer layer over the 64 models was 488 MPa (range= 248 to 840 MPa). MPS increased significantly with the addition of horizontal load components and with increasing cement thickness. In addition, MPS levels varied as a function of interactions between: proximal wall height reduction and load position; load position and cement thickness; core thickness and cement thickness; cement thickness and proximal wall height reduction; and core thickness, cement thickness and proximal wall height reduction.
Rational design of veneered structural ceramics must consider the complex geometry of the crown-tooth system and integrate the in uence of both the main effects and interactions among design parameters.
PMCID: PMC2814981  PMID: 19857888
all-ceramic; crowns; finite element analysis; factorial analysis
9.  Dental Care and Oral Disease in Alcohol Dependent Persons 
Dental/oral health of alcoholics and substance abusers is often neglected. It is not clear that alcohol dependence has effects on oral health beyond those expected in non-alcoholic persons of similar socioeconomic status (SES). Study objectives were to examine the personal dental care habits, ability to access professional dental care and the types of services received, and examine their effect on the oral health of alcoholics and substance abusers. Forty DSM-III-R diagnosed alcoholics and a comparison group of 25 non-alcoholic subjects matched for race, age, sex and SES were recruited. Subjects were medically healthy. Each subject received a comprehensive oral/dental examination and an interview was conducted to record personal dental hygiene habits, ability to access professional dental care and types of dental services provided.
No statistical differences were found between the oral care habits of the groups. Forty-four percent of all subjects had access to charity professional dental care. Tooth extraction was the main dental service they received. Seventy-five percent of subjects brushed their teeth once or more per day. In the non-alcoholic group, brushing frequency was inversely associated with plaque levels (p < 0.05); in the alcoholic group brushing frequency showed no statistical effect on plaque levels. Access to professional dental care was inversely associated with periodontitis in the alcoholic group (p < 0.05).
Alcohol dependence may increase plaque levels above that seen in race, sex, age and SES-matched controls, but professional dental care can limit the subsequent development of periodontal disease in these people.
PMCID: PMC2760312  PMID: 19150205
Dental care; Alcohol dependence; Drug abuse; Periodontal diseases
10.  Temporal Summation of Heat Pain in Temporomandibular Disorder Patients 
Journal of orofacial pain  2009;23(1):54-64.
One possible mechanism underlying myofascial temporomandibular disorders (TMD) is altered central nervous system processing of painful stimuli. The current study aimed to compare TMD cases to controls on two measures of central processing, i.e., temporal summation of heat pain and decay of subsequent aftersensations, following thermal stimulation in both a trigeminal and extratrigeminal area.
Using a “wind-up” (WU) protocol, 19 female TMD patients and 17 controls were exposed to 15 heat stimuli at a rate of 0.3 Hz. Numeric pain ratings were elicited after the 1st, 5th, 10th and 15th stimulus presentation and every 15 seconds after final presentation (aftersensations), for up to 2 minutes. In separate trials, the thermode was placed on the thenar eminence of the hand and the skin overlying the masseter muscle.
Groups did not differ with respect to the slope of WU when stimulated at either anatomic site, although asymptote occurred sooner for TMD patients than controls. In analysis of aftersensations, a significant group x site x time interaction was detected, in which TMD patients experienced more prolonged painful aftersensations than controls when stimulated on the skin overlying the masseter muscles.
These results are consistent with the presence of enhanced central sensitivity in TMD and suggest that this sensitivity may be largely confined to the region of clinical pain. This contrasts with conditions such as fibromyalgia, where central sensitivity appears to be widespread.
PMCID: PMC2652673  PMID: 19264036
Temporal summation; windup; aftersensations; chronic pain; temporomandibular disorders

Results 1-10 (10)