Longitudinal Magnetic Resonance Imaging-Based Superficial Femoral Artery Velocity Measurements in Diabetic and Nondiabetic Patients With Peripheral Artery Disease.

BACKGROUND: Longitudinal associations of noninvasive 2-dimensional phase-contrast magnetic resonance imaging (2D-PC-MRI) velocity markers of the superficial femoral artery (SFA) were analyzed along with the characteristics of peripheral artery disease (PAD). We hypothesized that the 2-year differences in MRI-based measures of SFA velocity were associated with longitudinal changes in markers of PAD. METHODS: A total of 33 (11 diabetic, 22 nondiabetic) patients with PAD with baseline and 2-year follow-up MRI scans were included in this secondary analysis of the Effect of Lipid Modification on Peripheral Artery Disease after Endovascular Intervention Trial (ELIMIT). Electrocardiographically gated 2D-PC-MRI was performed at a proximal and a distal location of the distal SFA territory. SFA lumen, wall, and total vessel volumes and the normalized wall index (NWI) were analyzed. RESULTS: Baseline characteristics did not differ between diabetic and nondiabetic PAD patients. Maximum proximal and distal SFA velocity measures did not differ between baseline and 2 years (41.98 interquartile range (IQR) (23.58-72.6) cm/s vs. 40.31 IQR (26.69-61.29) cm/s; P = 0.30). Pooled analysis (N = 33) showed that the 24-month change in the NWI was inversely associated with the 24-month change in the proximal maximal SFA velocity (beta = -168.36, R2 = 0.150, P value = 0.03). The 24-month change of the maximum velocity differences between the proximal and distal SFA locations was inversely associated with the 24-month changes in peak walking distance (beta = -0.003, R2 = 0.360, P value = 0.011). CONCLUSION: The 2-year change of SFA plaque burden is inversely associated with the 2-year change of proximal peak SFA blood flow velocity. 2D-PC-MRI measured SFA velocity may be of interest in assessing PAD longitudinally.

The influence of pediatricians' recommendation on caregivers' COVID-19 vaccine acceptance for children: A nationwide cross-sectional survey study from USA.

Background: The influence of pediatricians on parental acceptance of COVID-19 vaccine for children has not been well studied. We designed a survey to estimate the impact of pediatricians' recommendations on caregivers' vaccine acceptance while accounting for participants' socio-demographic and personal characteristics. The secondary objectives were to compare childhood vaccination rates among different age groups and categorize caregivers' concerns about vaccinating young (under-five) children. Overall, the study aimed to provide insight into potential pro-vaccination strategies that could integrate pediatricians to alleviate parental vaccine hesitancy. Methods: We conducted an online cross-sectional survey study using Redcap, in August 2022. We enquired COVID-19 vaccination status of the children in the family (≥five years). The survey questionnaire included socio-demographic and personal characteristics: age, race, sex, education, financial status, residence, healthcare worker, COVID-19 vaccination status and side effects, children's influenza vaccination status, and pediatricians' recommendations (1-5 scale). Logistic regression and neural network models were used to estimate the influence of socio-demographic determinants on children's vaccine status and build predictors' ranking. Results: The participants (N = 2,622) were predominantly white, female, middle-class, and vaccinated against COVID-19 (89%). The logistic regression model was significant vs. the null (likelihood-ratio χ2 = 514.57, p < 0.001, pseudo-R2 = .440). The neural network model also demonstrated strong prediction ability with a correct prediction rates of 82.9% and 81.9% for the training and testing models, respectively. Both models identified pediatricians' recommendations, self-COVID-19 vaccination status, and post-vaccination side effects as dominant predictors of caregivers' vaccine acceptance. Among the pediatricians, 70.48% discussed and had an affirmative opinion about COVID-19 vaccine for children. Vaccine acceptance was lower for children aged 5-8 years compared to older age groups (9-12 and 13-18 years), and acceptance varied significantly among the three cohorts of children (χ2 = 65.62, p < 0.001). About half of the participants were concerned about inadequate availability of vaccine safety information for under-five children. Conclusions: Pediatricians' affirmative recommendation was significantly associated with caregivers' COVID-19 vaccine acceptance for children while accounting for participants' socio-demographic characteristics. Notably, vaccine acceptance was lower among younger compared to older children, and caregivers' uncertainty about vaccine safety for under-five children was prevalent. Thus, pro-vaccination strategies might incorporate pediatricians to alleviate parental concerns and optimize poor vaccination rate among under-five children.

Evaluating Dermatology Residents Combined Oral Contraceptive Pill Prescribing Practices, Knowledge, and Comfort Level in the Management of Acne Vulgaris: A Cross-sectional Survey Study.

Objective: Combined oral contraceptive pills (COCs) are safe and effective therapies for females with acne vulgaris. Data is lacking regarding dermatology residents' COCs use. We aimed to evaluate dermatology residents' knowledge, comfort level, and prescribing practices of COCs in the management of acne vulgaris. Methods: A cross-sectional survey study was emailed to current dermatology residents in approved training programs and descriptive statistics were performed. Results: Most residents reported that COCs are an effective treatment for acne (160/170, 94.1%) but, less felt adequately trained on efficacy (105/170, 61.8%) and safety (72/170, 42.4%). 30 percent (51/170) of residents' attending physicians regularly prescribed COCs for acne. Half were comfortable counseling patients on adverse effects of COCs (86/170, 50.6%) while fewer were comfortable counseling on how to properly take COCs (66/170, 38.8%). 60 percent (102/170) felt comfortable prescribing COCs to healthy adolescents while 66.5 percent (113/170) were comfortable prescribing to adults. Limitations: Limitations include a small sample size, response bias, and inability to calculate an accurate response rate. Conclusion: This data suggests most residents recognize COCs are an effective treatment for acne vulgaris, but less feel adequately trained. Several knowledge gaps and potential educational interventions regarding COCs, including safety, efficacy, adverse effects, and contraindications, are highlighted.

Magnetic resonance imaging based superficial femoral artery velocity measurements in peripheral artery disease.

Peripheral artery disease (PAD) causes lower extremity dysfunction and is associated with an increased risk of cardiovascular mortality and morbidity. In this study, we analyzed how non-invasive 2-dimensional-phase-contrast magnetic resonance imaging (2D-PC-MRI) measured velocity markers of the distal superficial femoral artery (SFA) are associated with clinical and functional characteristics of PAD. A total of 70 (27 diabetic and 43 non-diabetic) PAD patients were included in this secondary analysis of data collected from the Effect of Lipid Modification on Peripheral Artery Disease after Endovascular Intervention Trial (ELIMIT). Electrocardiographically (ECG)-gated 2D-PC-MRI was performed at a proximal and a distal imaging location of the distal SFA. Baseline characteristics did not differ between diabetic and non-diabetic PAD patients. Claudication onset time (COT) was shorter in diabetic PAD patients compared to non-diabetics (0.56 (inter quartile range (IQR): 0.3, 2.04) minutes vs. 1.30 (IQR: 1.13, 2.15) minutes, p = 0.025). In a pooled analysis of all 70 PAD patients, maximum velocity was significantly higher in the proximal compared with the distal SFA segment (43.97 (interquartile range (IQR): 20.4, 65.2) cm/s; vs. 34.9 (IQR: 16.87, 51.71) cm/s; p < 0.001). The maximum velocities in both the proximal and distal SFA segments were significantly higher in diabetic PAD patients compared with non-diabetics (proximal: 53.6 (IQR: 38.73, 89.43) cm/s vs. 41.49 (IQR: 60.75, 15.9) cm/s, p = 0.033; distal: 40.8 (IQR: 23.7, 71.90) cm/s vs. 27.4 (IQR: 41.67, 12.54) cm/s, p = 0.012). Intra-observer variability, as assessed by intraclass correlation (ICC) analysis, was excellent for SFA mean and maximum velocities (0.996 (confidence interval [CI]: 0.996, 0.997); 0.999 (CI: 0.999, 0.999)). In conclusion, 2D-PC-MRI SFA velocity measures are reproducible and may be of interest in assessing diabetic and non-diabetic PAD patients.

The Influence of COVID-19 on Influenza and Respiratory Syncytial Virus Activities.

Background: Respiratory viral diseases have considerably declined since the COVID-19 outbreak, perhaps through influence by nonpharmaceutical interventions. We conducted a cross-sectional study using the CDC database to compare the pre- vs. post-pandemic flu activity (incidence) between the US states. Our secondary objectives were to estimate the association between flu activity and flu vaccination rates and compare the national trends of flu and RSV activities since the pandemic outbreak. Methods: We estimated the difference between pre-pandemic (April 2019-March 2020) and post-pandemic (April 2020-March 2021) flu activity between individual states using the Wilcoxon signed-rank test. The association between flu activity and immunization rates was also measured. Finally, parallel time trend graphs for flu and RSV activities were illustrated with a time series modeler. Results: The median (IQR) pre-pandemic flu activity was 4.10 (1.38), higher than the post-pandemic activity (1.38 (0.71)) (p-value < 0.001). There was no difference between pre-pandemic (45.50% (39.10%)) and post-pandemic (45.0% (19.84%)) flu vaccine acceptance (p-value > 0.05). Flu activity and vaccination rates were not associated (p-value > 0.05). Flu activity has declined since the COVID-19 outbreak, while RSV made a strong comeback in June 2021. Conclusion: Flu activity has significantly diminished throughout the pandemic while a sudden upsurge in RSV is a public health concern indicative of possible resurgence of other viruses. Flu vaccine acceptance neither changed during the pandemic nor influenced the diminished Flu activity.

The Influence of Sociodemographic Heterogeneity on the Perceptions of COVID-19: A Countrywide Survey Study in the USA.

Background: Sociodemographic factors such as age, race, education, family income, and sex have been reported to influence COVID-related perceptions, reflected by knowledge, stress, and preventive behavior. We conducted a US-based survey to estimate the difference in COVID-related perceptions among diverse sociodemographic groups and the influence of sociodemographic heterogeneity on COVID-related perceptions. Methods: The survey enquired about sociodemographic parameters and relevant information to measure knowledge, stress, and preventive behavior. COVID-perception scores among sociodemographic subgroups were compared with ANOVA (Bonferroni). The general linear model (GLM) was used to estimate the association among sociodemographic factors and COVID-related perceptions. Results: Females (75%) and White participants (78%) were the predominant (N = 3734). Females, White participants, wealthy, and educated participants demonstrated better knowledge, while participants of minority races, younger ages, low incomes, and females experienced high stress. Females, African-Americans, and educated participants better adopted preventive behaviors. Race, family income, and sex were the highest contributors to the predictive model. Sociodemographic determinants had statistically significant associations with knowledge (F-score = 7.72, p < 0.001; foremost predictor: race), stress (F-score = 16.46, p < 0.001; foremost predictor: income), and preventive behavior (GLM: F-score = 7.72, p < 0.001, foremost predictor: sex). Conclusion: Sociodemographic heterogeneity significantly influenced COVID-related perceptions, while race, family income, and sex were the strongest determinants of COVID-related perceptions.

Sociodemographic predictors of COVID-19 vaccine acceptance: a nationwide US-based survey study.

OBJECTIVES: Acceptance of COVID-19 vaccination is attributable to sociodemographic factors and their complex interactions. Attitudes towards COVID-19 vaccines in the United States are changing frequently, especially since the launch of the vaccines and as the United States faces a third wave of the pandemic. Our primary objective was to determine the relative influence of sociodemographic predictors on COVID-19 vaccine acceptance. The secondary objectives were to understand the reasons behind vaccine refusal and compare COVID-19 vaccine acceptance with influenza vaccine uptake. STUDY DESIGN: This was a nationwide US-based survey study. METHODS: A REDCap survey link was distributed using various online platforms. The primary study outcome was COVID-19 vaccine acceptance (yes/no). Sociodemographic factors, such as age, ethnicity, gender, education, family income, healthcare worker profession, residence regions, local healthcare facility and 'vaccine launch' period (pre vs post), were included as potential predictors. The differences in vaccine acceptance rates among sociodemographic subgroups were estimated by Chi-squared tests, whereas logistic regression and neural networks computed the prediction models and determined the predictors of relative significance. RESULTS: Among 2978 eligible respondents, 81.1% of participants were likely to receive the vaccine. All the predictors demonstrated significant associations with vaccine acceptance, except vaccine launch period. Regression analyses eliminated gender and vaccine launch period from the model, and the machine learning model reproduced the regression result. Both models precisely predicted individual vaccine acceptance and recognised education, ethnicity and age as the most important predictors. Fear of adverse effects and concern with efficacy were the principal reasons for vaccine refusal. CONCLUSIONS: Sociodemographic predictors, such as education, ethnicity and age, significantly influenced COVID-19 vaccine acceptance, and concerns of side-effects and efficacy led to increased vaccine hesitancy.

Perceived Stress, Knowledge, and Preventive Behaviors in Indian versus US-based Participants During COVID-19: A Survey Study.

Rationale: India and the USA, the worst affected countries by COVID-19, experienced very different pandemic courses. By 2020, COVID-19 cases had steadily declined in India, whereas the fight continued in the US. The people of India and the USA perhaps perceived threats very differently, influenced by their knowledge, available healthcare facilities, and social security. We conducted an online survey study to compare COVID-related perceptions between Indian participants (IND-P) and US-based participants (US-P). Methods: COVID-related perceptions such as stress, knowledge, and preventive behaviors were measured with specific questionnaires, and normalized scores were computed. T-tests were used to compare the perception scores, while the Kruskal-Wallis-H (KWH) tests were used to compare socioeconomic distributions between participants from two countries. Generalized linear model (GLM) adjusted for sociodemographic confounders estimated the association between the country of residence and COVID-perception. Results: The IND-P (N = 242) were younger and male-dominated compared with the US-P (N = 531) (age: KWH = 97.37, p < 0.0001, gender: KWH = 140.38, p < 0.0001). Positive attitudes toward preventive guidelines were associated with higher perceived risk and stress (r = 0.35, p < 0.001, and r = 0.21, p < 0.001, respectively) but not with the knowledge (r = -0.05, p = 0.14). Compared with the US-P, the IND-P had lower knowledge (5.19 ± 1.95 vs. 7.82 ± 1.35; t-test: p < 0.0001), higher stress (7.01 ± 1.51 vs. 6.07 ± 1.61; t-test: p < 0.0001), and better adherence to preventive guidelines (8.84 ± 1.30 vs. 8.34 ± 2.09; t-test: p = 0.0006). GLM demonstrated a significant association between the country and COVID-perception scores. Conclusion: The IND-P experienced higher stress and perceived threat during COVID-19 than the US-P, perhaps due to a lack of faith in the healthcare system and insecurity. Despite lower knowledge, the IND-P had better acceptance of preventive guidelines than the US-P.

Changes in Flavor Preference in a Cohort of Long-Term Electronic Cigarette Users.

Rationale: The use of electronic cigarettes (e-cigarettes) has rapidly increased in the United States, and thousands of e-cigarette flavors are available. However, there remains a dearth of evidence on e-cigarette flavor use patterns among older e-cigarette users.Objectives: This longitudinal study examined changes in flavor use patterns in long-term e-cigarette users, assessed self-reported adverse reactions, and evaluated users' anticipated reactions to possible U.S. Food and Drug Administration e-cigarette flavor regulatory scenarios.Methods: The study population was 383 adult participants who completed two online e-cigarette surveys in 2012-2014 (baseline survey) and in 2017-2019 (follow-up survey). In both surveys, participants were asked, "Thinking about your preferred liquid, what is the name of this liquid flavor?" and to list all flavors used in the past 30 days. Flavor preference was classified using the Penn State Three-Step Flavor Classification method. Participants reported adverse events (open-ended description) with the associated flavor. Regulatory scenarios were presented, and participants selected perceived actions from among a list of 15 options.Results: Participants' age averaged 44 ± 12 years; 86% were exclusive e-cigarette users, and 13% reported "poly-use" (i.e., e-cigarette and other tobacco product use). E-cigarette flavor preference migration occurred in all demographic groups: only 36-44% maintained a preference for their original flavor. Preference for tobacco and menthol or mint decreased over time (40% baseline vs. 22% follow-up); preference for fruit remained stable (23% baseline and follow-up), but chocolate/candy or other sweets preference significantly increased (16% baseline vs. 29% follow-up), and other flavors increased slightly. Migration to sweet flavors was more noticeable in younger adults (18-45 yr); exclusive e-cigarette users preferred sweet flavors more commonly than poly-users did (31% vs. 19%). Flavor-associated adverse reactions, mainly respiratory irritations, were reported by 26 (6.9%) participants. Nearly 50% of the participants reported that they would "find a way" to buy their preferred flavor or add flavoring agents themselves if nontobacco flavors were banned.Conclusions: Flavor migration toward sweet flavors occurred in long-term e-cigarette users, a trend most pronounced in younger and exclusive e-cigarette users. The anticipated maintenance of access to flavors despite regulation suggests an element of e-cigarette-related dependence that requires further evaluation. This information could help clinicians understand the health impacts of e-cigarette flavors, develop appropriate strategies for smoking cessation, and inform the U.S. Food and Drug Administration to plan future regulation of e-cigarette flavors.

Association between pulmonary function and left ventricular volume and function in duchenne muscular dystrophy.

INTRODUCTION: Duchenne muscular dystrophy (DMD) is characterized by absence of the subsarcolemmal protein dystrophin, present in skeletal muscles and cardiomyocytes. We hypothesized that progressive respiratory and left ventricular (LV) insufficiencies in DMD could be parallel and interrelated phenomena. METHODS: We conducted a retrospective chart review of 27 patients with DMD. Our primary objective was to compare the rates of decline between pulmonary function test (PFT) measures (forced expiratory volume in the first second, forced vital capacity, peak expiratory flow rate, maximal inspiratory/expiratory pressure) and echocardiographic estimates of LV end-diastolic volume and LV ejection fraction. RESULTS: The rates of decline/year of PFTs and LV estimates were not significantly different. Pulmonary function test measures of ventilatory efficiency and strength had strong intercorrelations. Pulmonary function tests and LV estimates had weak but statistically significant correlations. DISCUSSION: A comparable rate of decline in PFTs and LV indices in DMD provides evidence for concurrently progressive deterioration in respiratory and LV functions. Muscle Nerve, 2019.

The association of nocturnal hypoxia and an echocardiographic measure of pulmonary hypertension in children with sickle cell disease.

BACKGROUND: Pulmonary hypertension (PH) is multifactorial in origin and may develop early in children with sickle cell disease (C-SCD). Potential etiologies are hemolysis-induced endothelial dysfunction, left ventricular (LV) dysfunction, and chronic hypoxia. Nocturnal hypoxia (NH) in C-SCD is known to be a sequela of obstructive sleep apnea (OSA). The primary objective of this study is to correlate polysomnographic evidence NH with echocardiographic measures of PH in C-SCD. METHODS: We performed a retrospective chart review of 20 C-SCD (Hemoglobin SS), who had polysomnography and echocardiogram performed within a narrow time interval, and 31% of them had pre-existing cardiac conditions. Tricuspid regurgitant jet velocity (TRJV) ≥ 2.5 m/s was considered as an indicator of PH. RESULTS: Twenty-five percent of the subjects had NH. Forty percent of C-SCD, predominantly male, had evidence of PH based on an elevated TRJV. Children with NH compared to non-NH had significantly worse baseline hypoxemia (p < 0.001), higher TRJV (p = 0.005), and higher LV end-diastolic diameters (p = 0.009). The severity of NH was influenced by OSA. However, PH was not associated with OSA or duration of hydroxyurea therapy. CONCLUSION: Our study indicates that NH is associated with PH in C-SCD, and that screening for NH may help to identify C-SCD with higher morbidity risk.

The Association Between Female Smoking and Childhood Asthma Prevalence-A Study Based on Aggregative Data.

Aims: Socioeconomic and environmental factors influence childhood asthma prevalence across the world. In-depth epidemiological research is necessary to determine the association between asthma prevalence and socio-environmental conditions, and to develop public health strategies to protect the asthmatic children against the environmental precipitators. Our research was based on aggregative data and sought to compare the asthma prevalence between children of two different age-groups across the world and to identify the association among the key socio-environmental conditions with increased childhood asthma prevalence. Method: We included forty countries with available data on various socio-environmental conditions (2014-2015). Childhood asthma prevalence of two different age groups (6-7 and 13-14 years) were obtained from global asthma report 2014. Because of significant diversities, the selected countries were divided into two groups based on human developmental index (HDI), a well-recognized parameter to estimate the overall socioeconomic status of a country. Robust linear regression was conducted using childhood asthma prevalence as the dependent variable and female smoking prevalence, tertiary school enrollment (TSE), PM10 (particulate matter ≤10 µm in diameter) and gross domestic product (GDP) as predictors. Results: Asthma prevalence was not different between two age groups. Among all predictors, only female smoking prevalence (reflecting maternal smoking) was associated with asthma prevalence in the countries with lower socio-economic conditions (HDI), but not in the higher HDI group. The results were unchanged even after randomization. Conclusions: Childhood asthma prevalence did not change significantly with age. Female smoking may have a positive correlation with childhood asthma prevalence in lower HDI countries.

Socioeconomic and Environmental Predictors of Asthma-Related Mortality.

The prevalence of asthma-related mortality (ARM) varies significantly among different countries, possibly influenced by various socioeconomic and environmental conditions (SEC). In-depth epidemiological research is necessary to understand the causal relationship between different SECs and ARM and to develop public health strategies to reduce the global burden of asthma. Our research aimed to identify the key SECs which may be attributed to ARM worldwide and to study the relationship between ARM and asthma prevalence. We included twenty-two countries with available data on SECs (2014-2015) and divided them into four groups: Asia, Africa, Europe, and Miscellaneous (Australia and North and South America). Tertiary school enrollment (TSE), gross domestic product (GDP), air pollution index, and male and female smoking prevalence rates were analyzed as predictors of ARM, using multiple linear regression. We found that ARM and asthma prevalence had an inverse relationship and developing countries compared to developed countries experienced higher ARM despite having lower asthma prevalence. Asian and African countries, compared to Europe and Miscellaneous countries, experienced poorer SECs, possibly associated with higher ARM. Among SECs, TSE and GDP had strongest association with ARM. In conclusion, lack of education and uneven distribution of resources may have an influence on the increased ARM in developing countries.

Prolonged hippocampal cell death following closed-head traumatic brain injury in rats.

Traumatic brain injury (TBI) leads to enduring cognitive disorders. Although recent evidence has shown that controlled cortical impact in a rodent may induce memory deficits with prolonged cell death in the dentate gyrus (DG) of the hippocampus, few studies have reported long-term chronic hippocampal cell death following 'closed-head' TBI (cTBI), the predominant form of human TBI. Therefore, the aim of this study was to quantify terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL)(+) apoptotic hippocampal cells as well as hippocampal cells with hallmark morphological features of degenerating cells in a chronic setting of cTBI in rats. TUNEL assays and Cresyl violet staining were performed using 6-month post-TBI fixed hippocampal sections. Evidence of prolonged hippocampal cell death was shown by the presence of a significantly increased number of TUNEL(+) cells in the cornu ammonis 1-3 (CA1-CA3) and DG of the hippocampus compared with intact controls. In addition, Cresyl violet staining indicated a significantly elevated number of cells with the degenerative morphological features in all hippocampal subregions (CA1-CA3, hilus, and DG). These results suggest that prolonged cell death may occur in multiple regions of the hippocampus following cTBI.

Trigeminal neuroplasticity underlies allodynia in a preclinical model of mild closed head traumatic brain injury (cTBI).

Post-traumatic headache (PTH) following TBI is a common and often persisting pain disability. PTH is often associated with a multimodal central pain sensitization on the skin surface described as allodynia. However, the particular neurobiology underlying cTBI-induced pain disorders are not known. These studies were performed to assess trigeminal sensory sensitization and to determine if sensitization measured behaviorally correlated with detectable changes in portions of the trigeminal sensory system (TSS), particularly trigeminal nucleus, thalamus, and sensory cortex. Thermal stimulation is particularly well suited to evaluate sensitization and was used in these studies. Recent advances in the use of reward/conflict paradigms permit use of operant measures of behavior, versus reflex-driven response behaviors, for thermal sensitization studies. Thus, to quantitate facial thermal sensitization (allodynia) in the setting of acute TBI, the current study utilized an operant orofacial pain reward/conflict testing paradigm to assess facial thermal sensitivity in uninjured control animals compared with those two weeks after cTBI in a rodent model. Significant reductions in facial contact/lick behaviors were observed in the TBI animals using either cool or warm challenge temperatures compared with behaviors in the normal animals. These facial thermal sensitizations correlated with detectable changes in multiple levels of the TSS. The immunohistochemical (IHC) studies revealed significant alterations in the expression of the serotonin (5-HT), neurokinin 1 receptor (NK1R), norepinephrine (NE), and gamma-aminobutyric acid (GABA) in the caudal trigeminal nucleus, thalamic VPL/VPM nucleus, and sensory cortex of the orofacial pain pathways. There was a strong correlation between increased expression of certain IHC markers and increased behavioral markers for facial sensitization. The authors conclude that TBI-induced changes observed in the TSS are consistent with the expression of generalized facial allodynia following cTBI. To our knowledge, this is the first report of orofacial sensitization correlated with changes in selected neuromodulators/neurotransmitters in the TSS following experimental mild TBI.