Neighborhood effect and obesity in adult survivors of pediatric cancer: A report from the St. Jude lifetime cohort study

Survivors of childhood cancer are at risk for obesity, a condition potentially modifiable if dietary intake and physical activity are optimized. These health behaviors are likely influenced by neighborhood of residence, a determinant of access to healthy, affordable food and safe and easy exercise opportunities. We examined associations between neighborhood level factors and obesity among survivors in the St. Jude Lifetime cohort and community comparison group members. Persons with residential addresses available for geocoding were eligible for analysis (n = 2,265, mean age 32.5 [SD 9.1] years, 46% female, 85% white). Survivors completed questionnaires regarding individual behaviors; percent body fat was assessed via dual X-ray absorptiometry (obesity: ≥25% males; ≥35% females); neighborhood effect was characterized using census tract of residence (e.g., neighborhood socioeconomic status [SES], rurality). Structural equation modeling was used to determine associations between neighborhood effect, physical activity, diet, smoking, treatment exposures and obesity. Obese survivors (n = 1,420, 62.7%) were more likely to live in neighborhoods with lower SES (RR: 1.23, 95% CI: 1.10–1.38) and rural areas (RR: 1.22, 95% CI: 1.07–1.39) compared to survivors with normal percent body fat. Resource-poor neighborhoods (standardized effect: 0.06, p < 0.001) and cranial radiation (0.16, p < 0.001) had direct effects on percent body fat. Associations between neighborhood of residence and percent body fat were increased (0.01, p = 0.04) among individuals with a poor diet. Neighborhoods where survivors reside as an adult is associated with obesity. Interventions targeting survivors should incorporate strategies that address environmental influences on obesity.     

3,4-Methylenedioxymethamphetamine facilitates fear extinction learning

Acutely administered 3,4-methylenedioxymethamphetamine (MDMA, ‘ecstasy'') has been proposed to have long-term positive effects on post-traumatic stress disorder (PTSD) symptoms when combined with psychotherapy. No preclinical data support a mechanistic basis for these claims. Given the persistent nature of psychotherapeutic gains facilitated by MDMA, we hypothesized that MDMA improves fear extinction learning, a key process in exposure-based therapies for PTSD. In these experiments, mice were first exposed to cued fear conditioning and treated with drug vehicle or MDMA before extinction training 2 days later. MDMA was administered systemically and also directly targeted to brain structures known to contribute to extinction. In addition to behavioral measures of extinction, changes in mRNA levels of brain-derived neurotrophic factor (Bdnf) and Fos were measured after MDMA treatment and extinction. MDMA (7.8 mg kg⁻¹) persistently and robustly enhanced long-term extinction when administered before extinction training. MDMA increased the expression of Fos in the amygdala and medial prefrontal cortex (mPFC), whereas increases in Bdnf expression were observed only in the amygdala after extinction training. Extinction enhancements were recapitulated when MDMA (1  μg) was infused directly into the basolateral complex of the amygdala (BLA), and enhancement was abolished when BDNF signaling was inhibited before extinction. These findings suggest that MDMA enhances fear memory extinction through a BDNF-dependent mechanism, and that MDMA may be a useful adjunct to exposure-based therapies for PTSD and other anxiety disorders characterized by altered fear learning.     

Potential of mesenchymal stem cells alone,or in combination,to treat traumatic brain injury

Traumatic brain injury (TBI) causes death and disability in the United States and around the world. The traumatic insult causes the mechanical injury of the brain and primary cellular death. While a comprehensive pathological mechanism of TBI is still lacking, the focus of the TBI research is concentrated on understanding the pathophysiology and developing suitable therapeutic approaches. Given the complexities in pathophysiology involving interconnected immunologic, inflammatory, and neurological cascades occurring after TBI, the therapies directed to a single mechanism fail in the clinical trials. This has led to the development of the paradigm of a combination therapeutic approach against TBI. While there are no drugs available for the treatment of TBI, stem cell therapy has shown promising results in preclinical studies. But, the success of the therapy depends on the survival of the stem cells, which are limited by several factors including route of administration, health of the administered cells, and inflammatory microenvironment of the injured brain. Reducing the inflammation prior to cell administration may provide a better outcome of cell therapy following TBI. This review is focused on different therapeutic approaches of TBI and the present status of the clinical trials.     

Determining the utility of a smartphone-based gait evaluation for possible use in concussion management

ABSTRACT

Objectives: Our was objectives were to (1) assess the validity of a smartphone-based application to obtain spatiotemporal gait variables relative to an established movement monitoring system used previously to evaluate post-concussion gait, and (2) determine the test-retest reliability of gait variables obtained with a smartphone.

Methods: Twenty healthy participants (n = 14 females, mean age = 22.2, SD = 2.1 years) were assessed at two time points, approximately two weeks apart. Two measurement systems (inertial sensor system, smartphone application) acquired and analyzed single-task and dual-task spatio-temporal gait variables simultaneously. Our primary outcome measures were average walking speed (m/s), cadence (steps/min), and stride length (m) measured by the inertial sensor system and smartphone application.

Results: Correlations between the systems were high to very high (Pearson r = 0.77–0.98) at both time points, with the exception of dual-task stride length at time 2 (Pearson r = 0.55). Bland-Altman analysis for average gait speed and cadence indicated the average disagreement between systems was close to zero, suggesting little evidence for systematic bias between acquisition systems. Test-retest consistency measures using the smartphone revealed high to very high reliability for all measurements (ICC = 0.81–0.95).

Conclusions: Our results indicate that sensors within a smartphone are capable of measuring spatio-temporal gait variables similar to a validated three-sensor inertial sensor system in single-task and dual-task conditions, and that data are reliable across a two-week time interval. A smartphone-based application might allow clinicians to objectively evaluate gait in the management of concussion with high ease-of-use and a relatively low financial burden.     

Associations of sense of coherence with psychological distress and quality of life in inflammatory bowel disease

AIM: To investigate the relationship between sense of coherence, psychological distress and health related quality of life in inflammatory bowel disease (IBD).METHODS: This cross-sectional study enrolled a consecutive sample of 147 IBD (aged 45.1 ± 14.1 years; 57.1% female) patients recruited from a tertiary gastroenterology service. Sixty-four participants met diagnostic criteria for Crohn’s disease, while eighty-three patients had ulcerative colitis. Socio-demographic data (education, age, race, gender, gross monthly income and marital status), disease-related variables (illness activity, relapse rate in past 2 years, history of surgery and time since diagnosis), sense of coherence (Antonovsky’s SOC scale), psychological distress symptoms (Hospital Anxiety and Depression Scale) and health-related quality of life (HRQoL; WHOQOL-Bref) were assessed. Hierarchical multiple regression analyses were performed to identify factors that are independently associated with psychological distress and HRQoL in patients with IBD and to provide indications for possible moderating or mediating effects. In addition, formal moderation and mediation analyses (Sobel tests) were performed to confirm potential moderators/mediators of the relationship between SOC, psychological distress symptoms and HRQoL.RESULTS: Lower SOC scores (std beta= -0.504; P < 0.001), female gender (std beta = 0.176; P = 0.021) and White race (std beta = 0.164; P = 0.033) were independently associated with higher levels of depressive symptoms, while lower levels of SOC (std beta = -0.438; P < 0.001) and higher relapse rate (std beta = 0.161; P = 0.033) were independently associated with more severe anxiety symptoms. A significant interaction between time since diagnosis and SOC was found with regard to the severity of depressive or anxiety symptoms, as the interaction term (time since diagnosis X SOC) had beta coefficients of -0.191 (P = 0.009) and -0.172 (P = 0.026), respectively. Lower levels of anxiety symptoms (std beta = -0.369; P < 0.001), higher levels of SOC (std beta = 0.231; P = 0.016) and non-White race (std beta = -0.229; P = 0.006), i.e., mixed-race, which represented the reference category, were independently associated with higher levels of overall HRQoL. Anxiety symptoms were the most potent independent correlate of most aspects of HRQoL. In addition, anxiety mediated the association between SOC and satisfaction with health, as well as its relationship with physical, mental, and social relations HRQoL. Depressive symptoms also mediated the association between SOC and mental HRQoL.CONCLUSION: Our data indicated that SOC is an important construct, as it influences psychological distress and has significant albeit indirect effects on several HRQoL domains in IBD.     

The limits of passive motion are variable between and unrelated within normal tibiofemoral joints

Patient‐to‐patient differences should be accounted for in both clinical evaluations and computational models of knee laxity. Accordingly, the objectives were to determine how variable the laxities are between knees by determining the range of the internal–external (I‐E), varus–valgus (V‐V), anterior–posterior (A‐P), and compression–distraction (C‐D) limits of passive motion, and how related the laxities are within a knee by determining whether these limits are correlated with one another. The limits in I‐E (± 3 Nm), V‐V (± 5 Nm), A‐P (± 45 N), and C‐D (± 100 N) were measured in 10 normal human cadaveric knees at 0° to 120° flexion in 15° increments using a six degree‐of‐freedom load application system. The ranges from 15° to 120° flexion of the I‐E limits were greater than 3.6°, of the A‐P limits were greater than 1.8 mm, and of the varus limits were greater than 1.4°. The ranges from 30° to 120° flexion of the distraction limits were greater than 2.0 mm. Twenty‐four of the 28 pair‐wise comparisons between the limits had a correlation coefficient less than 0.65. These results demonstrate that a patient‐specific approach, including all degrees of freedom of interest, is necessary during clinical evaluations of laxity and when creating and validating computational models of the tibiofemoral joint. © 2015 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 33:1594–1602, 2015.