Cortisol has long been recognized as the “stress biomarker” in evaluating stress related disorders. Plasma, urine or saliva are the current source for cortisol analysis. The sampling of these biofluids is either invasive or has reliability problems that could lead to inaccurate results. Sweat has drawn increasing attention as a promising source for non-invasive stress analysis. A sensitive HPLC-MS/MS method was developed for the quantitation of cortisol ((11β)-11,17,21-trihydroxypregn-4-ene-3,20-dione) in human eccrine sweat. At least one unknown isomer that has previously not been reported and could potentially interfere with quantification was separated from cortisol with mixed mode RP HPLC. Detection of cortisol was carried out using atmospheric pressure chemical ionization (APCI) and selected reaction monitoring (SRM) in positive ion mode, using cortisol-9,11,12,12-D4 as internal standard. LOD and LOQ were estimated to be 0.04 ng ml⁻¹ and 0.1 ng ml⁻¹, respectively. Linear range of 0.10–25.00 ng ml⁻¹ was obtained. Intraday precision (2.5%–9.7%) and accuracy (0.5%–2.1%), interday precision (12.3%–18.7%) and accuracy (7.1%–15.1%) were achieved. This method has been successfully applied to the cortisol analysis of human eccrine sweat samples. This is the first demonstration that HPLC-MS/MS can be used for the sensitive and highly specific determination of cortisol in human eccrine sweat in the presence of at least one isomer that has similar hydrophobicity as cortisol. This study demonstrated that human eccrine sweat could be used as a promising source for non-invasive assessment of stress biomarkers such as cortisol and other steroid hormones.

Objective Office environments have been causally linked to workplace-related illnesses and stress, yet little is known about how office workstation type is linked to objective metrics of physical activity and stress. We aimed to explore these associations among office workers in US federal office buildings. Methods We conducted a wearable, sensor-based, observational study of 231 workers in four office buildings. Outcome variables included workers’ physiological stress response, physical activity and perceived stress. Relationships between office workstation type and these variables were assessed using structural equation modelling. Results Workers in open bench seating were more active at the office than those in private offices and cubicles (open bench seating vs private office=225.52 mG (31.83% higher on average) (95% CI 136.57 to 314.46); open bench seating vs cubicle=185.13 mG (20.16% higher on average) (95% CI 66.53 to 303.72)). Furthermore, workers in open bench seating experienced lower perceived stress at the office than those in cubicles (−0.27 (9.10% lower on average) (95% CI −0.54 to −0.02)). Finally, higher physical activity at the office was related to lower physiological stress (higher heart rate variability in the time domain) outside the office (−26.12 ms/mG (14.18% higher on average) (95% CI −40.48 to −4.16)). Conclusions Office workstation type was related to enhanced physical activity and reduced physiological and perceived stress. This research highlights how office design, driven by office workstation type, could be a health-promoting factor.

Endogenous glucocorticoids are essential for mobilizing energy resources, restraining inflammatory responses and coordinating behavior to an immune challenge. Impaired glucocorticoid receptor (GR) function has been associated with impaired metabolic processes, enhanced inflammation and exaggerated sickness and depressive-like behaviors. To discern the molecular mechanisms underlying GR regulation of physiologic and behavioral responses to a systemic immune challenge, GR^dim mice, in which absent GR dimerization leads to impaired GR–DNA-binding-dependent mechanisms but intact GR protein–protein interactions, were administered low-dose lipopolysaccharide (LPS). GR^dim-LPS mice exhibited elevated and prolonged levels of plasma corticosterone (CORT), interleukin (IL)-6 and IL-10 (but not plasma tumor necrosis factor-α (TNFα)), enhanced early expression of brain TNFα, IL-1β and IL-6 mRNA levels, and impaired later central TNFα mRNA expression. Exaggerated sickness behavior (lethargy, piloerection, ptosis) in the GR^dim-LPS mice was associated with increased early brain proinflammatory cytokine expression and late plasma CORT levels, but decreased late brain TNFα expression. GR^dim-LPS mice also exhibited sustained locomotor impairment in the open field, body weight loss and metabolic alterations measured by indirect calorimetry, as well as impaired thermoregulation. Taken together, these data indicate that GR dimerization-dependent DNA-binding mechanisms differentially regulate systemic and central cytokine expression in a cytokine- and time-specific manner, and are essential for the proper regulation and recovery of multiple physiologic responses to low-dose endotoxin. Moreover, these results support the concept that GR protein–protein interactions are not sufficient for glucocorticoids to exert their full anti-inflammatory effects and suggest that glucocorticoid responses limited to GR monomer-mediated transcriptional effects could predispose individuals to prolonged behavioral and metabolic sequelae of an enhanced inflammatory state.

This article examines the cures recorded in Lourdes, France, between 1858, the year of the Visions, and 1976, the date of the last certified cure of the twentieth century. Initially, the records of cures were crude or nonexistent, and allegations of cures were accepted without question. A Medical Bureau was established in 1883 to examine and certify the cures, and the medical methodology improved steadily in the subsequent years. We discuss the clinical criteria of the cures and the reliability of medical records. Some 1,200 cures were said to have been observed between 1858 and 1889, and about one hundred more each year during the “Golden Age” of Lourdes, 1890–1914. We studied 411 patients cured in 1909–14 and thoroughly reviewed the twenty-five cures acknowledged between 1947 and 1976. No cure has been certified from 1976 through 2006. The Lourdes phenomenon, extraordinary in many respects, still awaits scientific explanation. Lourdes concerns science as well as religion.

This Special Issue on Healing Spaces includes eight articles consisting of studies at the interface between design and health. The articles address some of the latest findings using state-of-the-art technologies, important outcomes for human health and wellbeing, and suggest exciting directions for the future of this research field.

The physiological impact of walking in nature was quantified via continuous heart rate variability (HRV), pre- and post-walk saliva cortisol measures, and self-reported mood and mindfulness scores for N = 17 participants who walked “The Green Road” at Walter Reed National Military Medical Center in Bethesda, Maryland. For N = 15 of the participants, HRV analysis revealed two main groups: group one individuals had a 104% increase (mean) in the root mean square standard deviation (RMSSD) and a 47% increase (mean) in the standard deviation of NN values (SDNN), indicating an overall reduction in physiological stress from walking the Green Road, and group two individuals had a decrease (mean) of 42% and 31% in these respective HRV metrics, signaling an increase in physiological stresses. Post-walk self-reported scores for vigor and mood disturbance were more robust for the Green Road than for a comparable urban road corridor and showed that a higher HRV during the walk was associated with improved overall mood. Saliva cortisol was lower after taking a walk for all participants, and it showed that walking the Green Road elicited a significantly larger reduction in cortisol of 53%, on average, when compared with 37% of walking along an urban road. It was also observed that the order in which individuals walked the Green Road and urban road also impacted their cortisol responses, with those walking the urban road before the Green Road showing a substantial reduction in cortisol, suggesting a possible attenuation effect of walking the Green Road first. These findings provide quantitative data demonstrating the stress-reducing effects of being in nature, thus supporting the health benefit value of providing access to nature more broadly in many settings.