Kathryn M. Taylor

Human exposure to nitro musks and the evaluation of their potential toxicity: an overview.

Synthetic nitro musks are fragrant chemicals found in household and personal care products. The use of these products leads to direct exposures via dermal absorption, as well as inhalation of contaminated dust and volatilized fragrances. Evidence also suggests that humans are exposed to low doses of these chemicals through oral absorption of contaminated liquids and foods. As these compounds are lipophilic, they and their metabolites, have been found not only in blood, but also breast milk and adipose tissue. After personal use, these environmentally persistent pollutants then pass through sewage treatment plants through their effluent into the environment.Little is known about the biological effects in humans after such a prolonged low dose exposure to these chemicals. While epidemiologic studies evaluating the effects of nitro musk exposures are lacking, there is limited evidence that suggest blood levels of nitro musks are inversely related to luteal hormone levels. This is supported by animal models and laboratory studies that have shown that nitro musks are weakly estrogenic. Nitro musks exposure has been associated with an increased risk of tumor formation in mice. The evidence suggests that while nitro musks by themselves are not genotoxic, they may increase the genotoxicity of other chemicals. However, animal models for nitro musk exposure have proven to be problematic since certain outcomes are species specific. This may explain why evidence for developmental effects in animals is conflicting and inconclusive. Given that animal models and cell-line experiments are suggestive of adverse outcomes, further epidemiologic studies are warranted.

Modification of the association between lead exposure and amyotrophic lateral sclerosis by iron and oxidative stress related gene polymorphisms

Abstract Our objective was to examine whether functional polymorphisms in hemochromatosis (HFE; H63D and C282Y), transferrin (TfC2), and glutathione-s-transferase Pi1 (GSTP1; Ile105Val) genes modify any lead-ALS association. We measured blood lead using atomic absorption spectroscopy and bone lead – a biomarker of cumulative lead exposure – using K-shell-X-ray fluorescence in 100 neurologist-confirmed ALS cases and 194 controls, the latter recruited as part of two separate studies; all subjects lived in New England. Participants were considered variant carriers or wild-type for each polymorphism. To assess effect modification, we included cross-product terms between lead biomarkers and each polymorphism in separate adjusted polytomous logistic regression models. Compared with wild-type, the odds ratio (OR) per 15.6 μg/g patella lead (interquartile range; IQR) was 8.24 (95% CI 0.94–72.19) times greater among C282Y variant carriers, and 0.34 (95% CI 0.15–0.78) times smaller among H63D variant carriers. Results were weaker for tibia lead. Compared with wild-type the OR per 2 μg/dl blood lead (IQR) was 0.36 (95% CI 0.19–0.68) times smaller among H63D variant carriers, and 1.96 (95% CI 0.98–3.92) times greater among GSTP1 variant carriers. In conclusion, we found that HFE and GSTP1 genotypes modified the association between lead biomarkers and ALS. Contrasting modification by the HFE polymorphisms H63D and C282Y may suggest that the modification is not simply the result of increased iron.

Cumulative lead exposure in community-dwelling adults and fine motor function: Comparing standard and novel tasks in the VA Normative Aging Study

BACKGROUND AND AIMS Lead exposure in children and occupationally exposed adults has been associated with reduced visuomotor and fine motor function. However, associations in environmentally exposed adults remain relatively unexplored. To address this, we examined the association between cumulative lead exposure-as measured by lead in bone-and performance on the grooved pegboard (GP) manual dexterity task, as well as on handwriting tasks using a novel assessment approach, among men in the VA Normative Aging Study (NAS). METHODS GP testing was done with 362 NAS participants, and handwriting assessment with 328, who also had tibia and patella lead measurements made with K-X-Ray Fluorescence (KXRF). GP scores were time (s) to complete the task with the dominant hand. The handwriting assessment approach assessed the production of signature and cursive lowercase l and m letter samples. Signature and lm task scores reflect consistency in repeated trials. We used linear regression to estimate associations and 95% confidence intervals (CI) with adjustment for age, smoking, education, income and computer experience. A backward elimination algorithm was used in the subset with both GP and handwriting assessment to identify variables predictive of each outcome. RESULTS The mean (SD) participant age was 69.1 (7.2) years; mean patella and tibia concentrations were 25.0 (20.7)μg/g and 19.2 (14.6)μg/g, respectively. In multivariable-adjusted analyses, GP performance was associated with tibia (β per 15μg/g bone=4.66, 95% CI: 1.73, 7.58, p=0.002) and patella (β per 20μg/g=3.93, 95% CI: 1.11, 6.76, p=0.006). In multivariable adjusted models of handwriting production, only the lm-pattern task showed a significant association with tibia (β per 15μg/g bone=1.27, 95% CI: 0.24, 2.29, p=0.015), such that lm pattern production was more stable with increasing lead exposure. GP and handwriting scores were differentially sensitive to education, smoking, computer experience, financial stability, income and alcohol consumption. CONCLUSIONS Long-term cumulative environmental lead exposure was associated with deficits in GP performance, but not handwriting production. Higher lead appeared to be associated with greater consistency on the lm task. Lead sensitivity differences could suggest that lead affects neural processing speed rather than motor function per se, or could result from distinct brain areas involved in the execution of different motor tasks.

Head injury at early ages is associated with risk of Parkinson's disease.

INTRODUCTION The literature on the effect of head injuries on the risk of PD is inconclusive. Some researchers have hypothesized that studies that have seen an effect are simply capturing injury related to pre-clinical PD. However in animal models brain inflammation, which can be initiated by head trauma, has been shown to produce PD-like effects. Furthermore, animal studies have found that early life inflammation in particular is of relevance for PD pathology. METHODS We conducted an unmatched case-control study of 379 neurologist confirmed PD patients and 230 controls from the greater Boston, Massachusetts area with questionnaire data on history of head injury and other covariates. We used multivariable logistic regression to estimate adjusted odds ratios (OR) and their corresponding 95% confidence intervals (CI) for PD. RESULTS When we excluded injuries that occurred less than 10 years prior to the diagnosis of PD (in order to avoid reverse causation), we found an increased risk of PD associated with a head injury that resulted in a loss of consciousness, but it did not reach statistical significance (OR = 1.57; 95% CI = 0.89-2.80). We found a significant (p = 0.04) effect of age at first head injury. For every 5 year earlier age at first head injury with loss of consciousness the OR for PD was 1.37 (95% CI: 1.01-1.86). CONCLUSION Our results suggest that head injury in early life increases the risk of PD.

Hernia recurrence following inguinal hernia repair in children

PURPOSE We aimed to describe the incidence, timing, and predictors of recurrence following inguinal hernia repair (IHR) in children. METHODS We used the TRICARE claims database, a national cohort of >3 million child dependents of members of the U.S. Armed Forces. We abstracted data on children <12y who underwent IHR (2005-2014). Our primary outcome was recurrence (ICD9-CM diagnosis codes). We calculated incidence rates for the population and stratified by age, time from repair to recurrence, and multivariable logistic regression to determine predictors. RESULTS Nine thousand nine hundred ninety-three children met inclusion criteria. Age at time of IHR was ≤1y in 37%, 2-3y in 23%, 4-5y in 16%, and 5-12y in 24%. Median follow-up time was 3.5y (IQR:1.6-6.1). 137 patients recurred (1.4%), with an incidence of 3.46 per 1000 person-years. Over half occurred in children 0-1y at repair (60%). The majority occurred within a year following repair (median 209 days [IQR:79-486]). Children 0-1y had 2.53 times greater odds of recurrence (compared to >5y). Children with multiple comorbidities had 5.45 times greater odds compared to those with no comorbidities. CONCLUSIONS The incidence of recurrence following IHR is 3.46 per 1000 person-years. The majority occurred within a year of repair. Children ≤1y and those with multiple comorbidities were at increased risk. LEVEL OF EVIDENCE Prognosis Study, Level II.

Using Touch Surgery to Improve Surgical Education in Low- and Middle-Income Settings: A Randomized Control Trial.

BACKGROUND/OBJECTIVE There is a severe surgical workforce shortage in Rwanda. Innovative educational tools must be introduced to train more residents and increase surgical capacity. Touch Surgery (TS) is a smartphone application that offers trainees the opportunity to practice operations; however, its effect is unknown in low- and middle-income countries. Our objectives were to determine the training effect of TS and its feasibility for use in surgery education in a low-resource setting. DESIGN We performed a randomized control trial of University of Rwanda surgical residents. Participants were blocked by postgraduate year and randomized to textbook or TS for learning tendon repair surgical technique. After the learning period, participants performed a tendon repair simulation, evaluated by blinded expert raters. Presimulation and postsimulation questionnaires tested their knowledge of tendon repair. SETTING The study was conducted at the simulation center of the University Teaching Hospital of Kigali, a tertiary referral and teaching hospital. PARTICIPANTS The study included University of Rwanda surgery residents. A total 27 of 51 surgery residents (52.94%) were enrolled. Participating residents represented the following specialties: general surgery (51.85%), orthopedics (40.74%), and urology (7.41%). RESULTS TS users scored 89.7% on tendon repair simulation, compared to textbook users who scored 63.4% (p < 0.001). Postsimulation questionnaires showed a significant improvement in cognitive scores for TS users (38.6%, p < 0.001), as compared to nonsignificant improvement for textbook users (15.9%, p = 0.304). About 92.3% of TS users reported that TS represents a useful training tool, and 61.5% reported that it would be a good or very good required part of the curriculum. CONCLUSIONS TS is a useful tool to improve both technical skills and knowledge of tendon repair procedure steps; however, its role may be limited to a supplemental tool as it does not improve the theoretical knowledge. TS has the potential to be implemented in a surgical academic curriculum in low- and middle-income countries.

Nonsteroidal Anti-Inflammatory Drug Prescriptions are Associated with Increased Stress Fracture Diagnosis in the U.S. Army Population

Stress fractures are common in military personnel and endurance athletes, and nonsteroidal anti‐inflammatory drug (NSAID) use is widespread in these populations. NSAIDs inhibit prostaglandin synthesis, which blunts the anabolic response of bone to physical activity and could therefore increase risk of stress fracture. The objective of this study was to determine whether prescribed NSAIDs were associated with stress fracture diagnoses among US Army soldiers. We also aimed to establish whether acetaminophen, an analgesic alternative to NSAIDs, was associated with stress fracture risk. A nested case‐control study was conducted using data from the Total Army Injury and Health Outcomes Database from 2002 to 2011 (n = 1,260,168). We identified soldiers with a diagnosis of stress fracture (n = 24,146) and selected 4 controls per case matched on length of military service (n = 96,584). We identified NSAID and acetaminophen prescriptions 180 to 30 days before injury (or match date). We also identified soldiers who participated in basic combat training (BCT), a 10‐week period of heightened physical activity at the onset of Army service. Among these individuals, we identified 9088 cases and 36,878 matched controls. Conditional logistic regression was used to calculate incident rate ratios (RR) for stress fracture with adjustment for sex. NSAID prescription was associated with a 2.9‐fold increase (RR = 2.9, 95% confidence interval [CI] 2.8–2.9) and acetaminophen prescription with a 2.1‐fold increase (RR = 2.1, 95% CI 2.0–2.2) in stress fracture risk within the total Army population. The risk was more than 5‐fold greater in soldiers prescribed NSAIDs (RR = 5.3, 95% CI 4.9–5.7) and more than 4‐fold greater in soldiers prescribed acetaminophen (RR = 4.4, 95% CI 3.9–4.9) during BCT. Our results reveal an association between NSAID and acetaminophen prescriptions and stress fracture risk, particularly during periods of heightened physical activity. Prospective observational studies and randomized controlled trials are needed to support these findings before clinical recommendations can be made.

Concussion History and Cognitive Function in a Large Cohort of Adolescent Athletes

Background: The incidence of reported concussions in the adolescent population is increasing, yet research on the effects of concussions in this population is minimal and inconclusive. Purpose: To assess the association between concussion and performance on a cognitive test battery. Study Design: Cross-sectional study; Level of evidence, 3. Methods: Using multivariate models, the authors assessed the association between concussion and performance on a cognitive test battery among 5616 high school and junior high school athletes. The researchers utilized a global cognitive score and scores for 5 domains: verbal memory, visual memory, visual motor, reaction time, and impulse control. Each cognitive score was converted to a z score with the mean and SD of the nonconcussed population. Results from each model were then interpreted as change in the standardized unit score. In the models, concussion was evaluated as ever having a concussion, number of concussions, time since last concussion, and age at first concussion. Results: Ever having a concussion was associated with a mean decrease of 0.11 standardized units (95% CI, −0.20 to −0.01) on the global cognitive score and lower scores in all cognitive domains. Each additional concussion was associated with lower scores on global cognitive function (effect estimate, −0.06; 95% CI, −0.11 to −0.02), verbal memory, visual memory, and impulse control. Concussion in early childhood was associated with lower global cognition (effect estimate, −0.05; 95% CI, −0.08 to −0.01), visual memory, and motor visual scores as compared with concussions in later childhood. The associations between time since last concussion and cognitive test scores were nonlinear, and on all tests, lower scores were observed even ≥1 year after the concussion. Conclusion: On the basis of objective performance metrics for cognitive function, concussions had a more persistent effect on cognitive function than previously thought. The age at which an individual has his or her first concussion may be an important factor in determining long-lasting cognitive effects.