Urban Nature Experiences Reduce Stress in the Context of Daily Life Based on Salivary Biomarkers.

Stress reduction through contact with nature is well established, but far less is known about the contribution of contact parameters - duration, frequency, and nature quality. This study describes the relationship between duration of a nature experience (NE), and changes in two physiological biomarkers of stress - salivary cortisol and alpha-amylase. It is the first study to employ long-term, repeated-measure assessment and the first evaluation wherein study participants are free to choose the time of day, duration, and the place of a NE in response to personal preference and changing daily schedules. During an 8-week study period, 36 urban dwellers were asked to have a NE, defined as spending time in an outdoor place that brings a sense of contact with nature, at least three times a week for a duration of 10 min or more. Their goal was compliance within the context of unpredictable opportunity for taking a nature pill. Participants provided saliva samples before and after a NE at four points over the study period. Before-NE samples established the diurnal trajectory of each stress indicator and these were in line with published outcomes of more closely controlled experiments. For salivary cortisol, an NE produced a 21.3%/hour drop beyond that of the hormone's 11.7% diurnal drop. The efficiency of a nature pill per time expended was greatest between 20 and 30 min, after which benefits continued to accrue, but at a reduced rate. For salivary alpha-amylase, there was a 28.1%/h drop after adjusting for its diurnal rise of 3.5%/h, but only for participants that were least active sitting or sitting with some walking. Activity type did not influence cortisol response. The methods for this adaptive management study of nature-based restoration break new ground in addressing some complexities of measuring an effective nature dose in the context of normal daily life, while bypassing the limitations of a clinical pharmacology dose-response study. The results provide a validated starting point for healthcare practitioners prescribing a nature pill to those in their care. This line of inquiry is timely in light of expanding urbanization and rising healthcare costs.

Estimation of delay time in survival data with delayed treatment effect.

In randomized controlled trials with delayed treatment effect, there is a delay period before the experimental therapy starts to exhibit a beneficial effect. The phenomenon of delayed treatment effect is often observed in the emerging and important field of immuno-oncology. It is important to estimate the duration of delay as this information helps in characterizing the pattern of comparative treatment effect, understanding the mechanism of action of the experimental therapy, and forming optimal treatment strategies. For a fixed delay time, we propose a maximum likelihood estimator and evaluate its asymptotic properties via simulation. We further evaluate two functions that link the pre- and postdelay hazard ratios to the average hazard ratio given a fixed delay time. For the case of random delay time, where the delay time may vary from patient to patient, we propose a semiparametric joint survival model for delay time and event time to estimate the mean delay time and the postdelay hazard ratio, assuming a Beta distribution for the delay time. We describe an extension of the model to estimate subgroup-specific mean delay times. Simulation study and application to data from a clinical trial in colon cancer patients demonstrate the robustness of the proposed model.

Diabetes-Specific Regulation of Adipocyte Metabolism by the Adipose Tissue Extracellular Matrix.

Context: The role of the extracellular matrix (ECM) in regulating adipocyte metabolism in the context of metabolic disease is poorly defined. Objective: The objective of this study was to define the metabolic phenotype of adipocytes associated with human diabetes (DM) and the role of the ECM in regulating adipocyte metabolism. Design: Adipose tissues from obese patients were studied in standard 2-dimensional (2D) cell culture and an in vitro model of decellularized adipose tissue ECM repopulated with human adipocytes, and results were correlated with DM status. Setting: This study was conducted at the Academic University Medical Center and Veteran's Administration Hospital. Patients: Seventy patients with morbid obesity undergoing bariatric surgery were included in the study. Interventions: Visceral and subcutaneous adipose tissues were collected at the time of bariatric surgery. Outcome measures: This study used metabolic assays for glucose uptake, lipolysis, and lipogenesis in adipocytes in 2D cell culture and 3-dimensional ECM culture. Results: Adipocytes from subjects with DM manifest decreased glucose uptake and decreased lipolysis in 2D culture. ECM supports differentiation of mature adipocytes and recapitulates DM-specific differences in adipocyte metabolism observed in 2D culture. ECM from subjects without DM partially rescues glucose uptake and lipolytic defects in adipocytes from subjects with DM, whereas ECM from subjects with DM impairs glucose uptake in adipocytes from subjects without DM. Conclusions: DM is associated with adipocyte metabolic dysfunction. The ECM regulates adipocyte metabolism. Nondiabetic ECM rescues metabolic dysfunction in DM adipocytes, whereas DM ECM imparts features of metabolic dysfunction to nondiabetic adipocytes. These findings suggest the ECM as a target for manipulating adipose tissue metabolism.

Sleep Hygiene Practices and Bedtime Resistance in Low-Income Preschoolers: Does Temperament Matter?

This study examined sleep hygiene practices and bedtime resistance and tested whether associations differed by child temperament. Parents of Head Start preschoolers (n = 374, 56% non-Hispanic white) completed the Going to Bed subscale of the Children's Sleep-Wake Scale (GTB; higher score reflects less bedtime resistance), Children's Sleep Hygiene Scale (CSHS; higher score reflects better sleep hygiene), and Child Behavior Questionnaire (Anger, Activity, Impulsivity subscales indicated difficult temperament). Monte Carlo simulation adjusted for demographic covariates tested associations of CSHS with GTB in children with more- vs. less-difficult temperaments. Children with more- vs. less-difficult temperaments experienced worse sleep hygiene (p < .0001) and had more bedtime resistance (p < .0001). Among children with more difficult temperaments, better sleep hygiene was linearly associated with less bedtime resistance (ß = 1.28, 95% CI 0.77, 1.78). Among children with less difficult temperaments, the association followed a piecewise linear trend: sleep hygiene was not associated with bedtime resistance when CSHS scores were < 4.1 (ß = 0.15, 95% CI -4.87, 3.13), but for CSHS scores ≥ 4.1, an increase in CSHS was associated with lower bedtime resistance (ß = 1.33, 95% CI 1.00, 1.79). Consistent sleep hygiene is associated with less bedtime resistance and may be helpful in reducing bedtime resistance among children with more difficult temperaments.