Wellbuilt for wellbeing: Controlling relative humidity in the workplace matters for our health.

This study offers a new perspective on the role of relative humidity in strategies to improve the health and wellbeing of office workers. A lack of studies of sufficient participant size and diversity relating relative humidity (RH) to measured health outcomes has been a driving factor in relaxing thermal comfort standards for RH and removing a lower limit for dry air. We examined the association between RH and objectively measured stress responses, physical activity (PA), and sleep quality. A diverse group of office workers (n = 134) from four well-functioning federal buildings wore chest-mounted heart rate variability monitors for three consecutive days, while at the same time, RH and temperature (T) were measured in their workplaces. Those who spent the majority of their time at the office in conditions of 30%-60% RH experienced 25% less stress at the office than those who spent the majority of their time in drier conditions. Further, a correlational study of our stress response suggests optimal values for RH may exist within an even narrower range around 45%. Finally, we found an indirect effect of objectively measured poorer sleep quality, mediated by stress responses, for those outside this range.

Heart rate variability and inflammation: A meta-analysis of human studies.

The inflammatory reflex is known as the body's primary defense against infection and has been implicated in a number of diseases. The magnitude of the inflammatory response is important, as an extreme or insufficient response can be differentially harmful to the individual. Converging evidence suggests that the autonomic nervous system (ANS) regulates the inflammatory reflex. Heart rate variability (HRV) can be separated into components that primarily reflect parasympathetic (PNS) or vagal activity (i.e., indices of vagally mediated HRV) and a combination of both sympathetic (SNS) and PNS influences. Given the physiological relation between the vagus and inflammatory processes, one would expect to find higher HRV, especially indices of vagally-mediated HRV, to be associated with decreased levels of inflammation via the cholinergic anti-inflammatory pathway. However, existing findings here are mixed, such that studies have also shown a positive association between indices of HRV and markers of inflammation. Therefore, the present meta-analysis aimed to synthesize existing studies, estimating the general direction and strength of the relationship between different indices of HRV and inflammatory markers. A systematic search of the literature yielded 2283 studies that were screened for inclusion eligibility (159 studies eligible for inclusion); in sum, 51 studies reported/provided adequate information for inclusion in meta-analyses. Results generally showed negative associations between indices of HRV and markers of inflammation. In this regard, the standard deviation of R-R intervals (SDNN) and power in the high frequency band of HRV (HF-HRV) showed the strongest and most robust associations with inflammatory markers compared to other time- and frequency-domain measures of HRV. Overall, we propose that indices of HRV can be used to index activity of the neurophysiological pathway responsible for adaptively regulating inflammatory processes in humans.

Effects of office workstation type on physical activity and stress.

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.

Designing Interiors to Mitigate Physical and Cognitive Deficits Related to Aging and to Promote Longevity in Older Adults: A Review.

BACKGROUND: With the increasing global population of older adults, there is a need for environmental interventions that directly affect their physical, psychological, and emotional well-being to help them maintain or regain their independence and autonomy - all of which promote longevity. METHODS: To better understand potential opportunities and challenges associated with interior design and "future homes" that may promote well-being, aging in place, and independent living in older adults, the authors reviewed relevant literature and included their own expert opinions from a multidisciplinary point of view including interior design, wellness, and engineering. RESULTS: After summarizing existing environmental interventions for the aging population and their effectiveness, this review reveals knowledge gaps in interior design for the well-being and longevity of older adults followed by a discussion of opportunities for future research that may fill these gaps. Some of these opportunities include finding habilitative design strategies that identify and address unique situational needs of each user, advancing multidisciplinary fields such as environmental gerontology that recreate security and independence for older adults even outside of their homes, implementing technically advanced design strategies, which are flexible and adaptive to individual needs; and integrating the Internet of things (IoT) into living environments, including voice-activated command technologies to improve seniors' central role in enabling an optimized healthcare ecosystem. CONCLUSIONS: Knowledge of current evidence regarding the impact of different environmental factors may hasten adaptation of well-designed innovations that can provide optimal healing and living environments for the aging population. By effectively addressing older adults' unique and specialized needs, design practitioners can become an indispensable part of their medical, social, and environmental team. One of the rapidly developing infrastructures promising to revolutionize the design of "future homes" is the IoT. While it is at an early stage of development, ultimately we envisage a connected home using voice-controlled technology and Bluetooth-radio-connected add-ons, to augment much of what home health does today. Bringing these approaches together into an effective strategy for a model of effective geriatric care is important and needs to become an integral part of both design education and practice.

Neural regulation of innate immunity: a coordinated nonspecific host response to pathogens.

The central nervous system (CNS) regulates innate immune responses through hormonal and neuronal routes. The neuroendocrine stress response and the sympathetic and parasympathetic nervous systems generally inhibit innate immune responses at systemic and regional levels, whereas the peripheral nervous system tends to amplify local innate immune responses. These systems work together to first activate and amplify local inflammatory responses that contain or eliminate invading pathogens, and subsequently to terminate inflammation and restore host homeostasis. Here, I review these regulatory mechanisms and discuss the evidence indicating that the CNS can be considered as integral to acute-phase inflammatory responses to pathogens as the innate immune system.

Quantification of cortisol in human eccrine sweat by liquid chromatography - tandem mass spectrometry.

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 ((11ß)-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.

New and Future Directions in Integrative Medicine Research Methods with a Focus on Aging Populations: A Review.

This review discusses existing and developing state-of-the-art noninvasive methods for quantifying the effects of integrative medicine (IM) in aging populations. The medical conditions of elderly patients are often more complex than those of younger adults, making the multifaceted approach of IM particularly suitable for aging populations. However, because IM interventions are multidimensional, it has been difficult to examine their effectiveness and mechanisms of action. Optimal assessment of IM intervention effects in the elderly should include a multifaceted approach, utilizing advanced analytic methods to integrate psychological, behavioral, physiological, and biomolecular measures of a patient's response to IM treatment. Research is presented describing methods for collecting and analyzing psychological data; wearable unobtrusive devices for monitoring heart rate variability, activity and other behavioral responses in real time; immunochemical methods for noninvasive molecular biomarker analysis, and considerations and analytical approaches for the integration of these measures. The combination of methods and devices presented in this review will provide new approaches for evaluating the effects of IM interventions in real-life ambulatory settings of older adults, and will extend the concept of mobile health to the domains of IM and healthy aging.

The Lourdes medical cures revisited.

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.

Discovery of associative patterns between workplace sound level and physiological wellbeing using wearable devices and empirical Bayes modeling.

We conducted a field study using multiple wearable devices on 231 federal office workers to assess the impact of the indoor environment on individual wellbeing. Past research has established that the workplace environment is closely tied to an individual's wellbeing. Since sound is the most-reported environmental factor causing stress and discomfort, we focus on quantifying its association with physiological wellbeing. Physiological wellbeing is represented as a latent variable in an empirical Bayes model with heart rate variability measures-SDNN and normalized-HF as the observed outcomes and with exogenous factors including sound level as inputs. We find that an individual's physiological wellbeing is optimal when sound level in the workplace is at 50 dBA. At lower (<50dBA) and higher (>50dBA) amplitude ranges, a 10 dBA increase in sound level is related to a 5.4% increase and 1.9% decrease in physiological wellbeing respectively. Age, body-mass-index, high blood pressure, anxiety, and computer use intensive work are person-level factors contributing to heterogeneity in the sound-wellbeing association.

Development of a sensitive microarray immunoassay for the quantitative analysis of neuropeptide Y.

A direct competitive immunoassay in an antibody microarray format was developed for the sensitive detection of neuropeptide Y (NPY) and employed in the analysis of NPY in human sweat samples. This is the first demonstration that antibody microarray, as a powerful multiplex analysis tool, can be used for the sensitive determination of NPY and potentially other neuropeptides. 400 pg/mL of dibiotinylated NPY and 0.1 mg/mL spotting capture antibody were found to offer the best performance, yielding a sensitivity of 50 pg/mL and a linear dynamic range of 0.1-100 ng/mL for NPY. Evaluation of matrix effects by using artificial sweat revealed that dialysis is necessary for analyzing NPY in human sweat samples with microarray immunoassay. In a preliminary application, 50-210 pg/mL of NPY was detected in sweat samples collected with Macroduct collectors. This study indicates that antibody microarrays can be used for NPY analysis and that human sweat could be a valuable sample source for biomarker and proteomics studies, especially when noninvasive human sample collection is preferable.

Caregiving burden, stress, and health effects among family caregivers of adult cancer patients.

Unlike professional caregivers such as physicians and nurses, informal caregivers, typically family members or friends, provide care to individuals with a variety of conditions including advanced age, dementia, and cancer. This experience is commonly perceived as a chronic stressor, and caregivers often experience negative psychological, behavioral, and physiological effects on their daily lives and health. In this report, we describe the experience of a 53-year-old woman who is the sole caregiver for her husband, who has acute myelogenous leukemia and was undergoing allogeneic hematopoietic stem cell transplantation. During his intense and unpredictable course, the caregiver's burden is complex and complicated by multiple competing priorities. Because caregivers are often faced with multiple concurrent stressful events and extended, unrelenting stress, they may experience negative health effects, mediated in part by immune and autonomic dysregulation. Physicians and their interdisciplinary teams are presented daily with individuals providing such care and have opportunity to intervene. This report describes a case that exemplifies caregiving burden and discusses the importance of identifying caregivers at risk of negative health outcomes and intervening to attenuate the stress associated with the caregiving experience.

Tissue expression of steroid hormone receptors is associated with differential immune responsiveness.

Glucocorticoids have been used as treatments against a number of diseases, especially autoimmune/inflammatory conditions in which the immune system is overactive. These treatments have varying degrees of responsiveness among individuals and in different tissues (including brain); therefore, it is important to determine what could account for these differences. In this study, we evaluated expression of stress hormone receptors in immune cells from lymphoid and non-lymphoid tissues (including brain) as a possible explanation. We analyzed leukocytes (CD45(+)) in kidney, liver, spleen, and thymus tissues from healthy mice for expression of the receptor for stress hormone (glucocorticoid-GR) as well as other steroid hormones (androgen-AR, progesterone-PR) and found that all tissues expressed these steroid hormone receptors but with varying patterns. To determine whether tissue-specific differences were related to immune cell composition, we examined steroid hormone receptor expression in T lymphocytes from each of these tissues and found similar patterns of expression in these cells regardless of tissue source. Because glucocorticoids can also impact brain function, we further examined expression of the stress hormone receptor in brain tissue and found GR expressed in immune cells at this site. In order to investigate the potential impact in an area of neuropathology, we utilized a mouse model of West Nile Virus (WNV). We observed pathological changes in brains of WNV-infected animals and T lymphocytes in the areas of inflammation; however, these cells did not express GR. These data indicate that tissue-specific differences in steroid hormone receptor expression by immune cells could determine responsiveness to steroid hormone treatment.

Effect of Workstation Type on the Relationship Between Fatigue, Physical Activity, Stress, and Sleep.

OBJECTIVE: This study examined office workstation types' impact on the relationship between fatigue and three health metrics: physical activity, stress, and sleep quality. METHODS: Data from 225 office workers were collected for perceived fatigue, perceived sleep quality (Pittsburgh Sleep Quality Index [PSQI]), physiological stress response (standard deviation of heart rate variability [HRV]), and physical activity (total activity in minutes) during three consecutive workdays. Stress and physical activity were measured using chest-worn sensors. Workers were then categorized as tired or not-tired based on the median of the fatigue rating. RESULTS: Among tired workers, open-bench seating workers had increased physical activity, improved sleep quality, and reduced stress compared with workers in private offices and cubicles. CONCLUSIONS: Office workstation types influence physical activity and levels of stress during work hours, which in turn affect sleep quality.

Neural aspects of immunomodulation: focus on the vagus nerve.

Inflammation and immunity have been implicated in a wide variety of diseases and disorders ranging from Alzheimer's disease to cardiovascular disease to hemorrhagic shock. In this review, we will briefly consider the evidence for the neural concomitants of immunomodulation. First, we will briefly review the anatomy and physiology of neural-immune communication. Evidence for the somatotopic organization of the vagus nerve and for pain processes suggests that such an organization may be relevant for the investigation of the neural concomitants of immunity. Then we will provide an overview of what is known from both animal and human studies including neuroimaging and clinical studies. Finally, we will discuss some of the challenges and opportunities in this exciting area of investigation.

Effects of the physical work environment on physiological measures of stress.

AIMS: In this study we investigated the effects of the physical work environment on two physiological measures of the stress response. METHODS AND RESULTS: Circadian variations in vagally mediated heart rate variability (HRV) and the morning rise in cortisol were evaluated in 60 participants working in a government building either in a traditional (individual offices and old cubicles; n=40) or a modern workspace (individualized cubicles with improved views and lighting; n=20). Results revealed significant linear (B=-1.03; confidence interval: -1.05 to -1.01, P<0.05) and quadratic (B=1.001; confidence interval: 1.0004-1.002, P<0.05) trends by office type interactions for indices of vagally mediated HRV. Individuals in the old office space had flatter slopes and thus less circadian variation including less HRV at night, and a larger rise in cortisol upon awakening compared with those in the new office space. CONCLUSION: These results indicate that physical features of the work environment may affect two aspects of the physiological stress response: circadian variations in HRV and the morning rise in cortisol. These findings have important social, economic, and public health implications for work environment risk factors on health.

Evaluation of stress systems by applying noninvasive methodologies: measurements of neuroimmune biomarkers in the sweat, heart rate variability and salivary cortisol.

The two main arms of the stress system include the autonomic nervous system (ANS) and the hypothalamic-pituitary-adrenal (HPA) axis. These two neural stress systems coordinate the response of many other physiological systems to a stressor, including the immune and cardiovascular systems, bringing the body back to homeostasis. The nervous and immune systems communicate with each other in a bidirectional manner. In this review, we will discuss the use of noninvasive methods to evaluate the immune system, ANS and HPA axis. Collection of sweat and saliva, and measurement of heart rate variability are noninvasive methods that can be applied to evaluate neuroimmune interactions. Recently, we validated a new methodology to simultaneously evaluate a large array of neural and immune biomarkers in sweat, collected through cutaneous sweat patches and measured by recycling immunoaffinity chromatography. Noninvasive and ambulatory methodologies of biomarker collection can overcome several limitations intrinsic to invasive methods, such as reducing the stress triggered by collection itself and allowing a wider application to field and community-based settings. Ultimately, simultaneous evaluation of neural and immune systems with noninvasive techniques will help elucidate the underlying interactions of these systems and their role in disease susceptibility and progression of stress-related disorders.

Healing Spaces: Designing Physical Environments to Optimize Health, Wellbeing, and Performance.

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.

LCMS Measurement of Steroid Biomarkers Collected from Palmar Sweat.

Human eccrine sweat contains numerous biomarkers which can provide information on health, performance, and aging. Non-invasive collection and measurement of biomarkers has become especially important in recent times given viral outbreaks like SARS-CoV-2. In the current study we describe a method of sweat collection from palmar surfaces in participants via surface capture using glass beads and the resulting analysis of biomarkers from very low volumes of sweat using liquid chromatography mass spectrometry with selected ion monitoring. Study participants underwent a cognitive and physical stress task with easy and hard conditions with sweat being collected after each task. Resulting analysis found a signal for 22 steroid biomarkers and we report detailed information on selected biomarkers, given their applicability to timely real-world exemplars, including cortisol, dehydroepiandrosterone, allopregnanolone, estrone, aldosterone, and 20α/ß-dihydrocortisone.

Flow cytometry as a tool for measurement of steroid hormone receptor protein expression in leukocytes.

Measurement of protein expression in live, intact cells using flow cytometry (FC) has been employed for several decades in the areas of immunology, cell biology, and molecular biology. More recently, this technique has found appreciation in applied scientific fields, including cancer biology and endocrinology, to serve as a tool for identifying cells more likely to respond to specific treatments. FC, also referred to as fluorescence-activated cell sorting (FACS), is an antibody-based method that provides the user with an ability to identify proteins expressed on surfaces of cells as well as in the cytoplasm, including steroid hormone receptors. This technique is most useful for examining specific cell types in a heterogeneous population and therefore can be used to identify cells more likely to respond to treatments based on expression of the appropriate receptor. Isolation of purified subpopulations for further manipulation and investigation of functional capacity is also possible using a cell sorter, which uses similar technology to isolate cells for use by the researcher. This is especially important for studying responses of less abundant cell populations in tissues that express high levels of a target protein or receptor of interest. Furthermore, FACS analysis is clinically useful to identify and isolate responsive cell populations, which may be less appreciable in whole tissues because of the diluting effects of surrounding, nonresponding cell types. Immune cells are commonly utilized as a source of cell populations in the FC technique and have previously been shown to express steroid hormone receptors and respond to steroid hormone treatment. Here, we demonstrate that FC is a useful tool for identifying immune cells expressing steroid hormone receptor protein. This method can also be easily expanded to include other, nonimmune cell populations to address specific research questions related to steroid hormone receptor biology.

The role of glucocorticoids and progestins in inflammatory, autoimmune, and infectious disease.

A bidirectional communication exists between the CNS and the immune system. The autonomic nervous system, through neurotransmitters and neuropeptides, works in parallel with the hypothalamic-pituitary-adrenal axis through the actions of glucocorticoids to modulate inflammatory events. The immune system, through the action of cytokines and other factors, in turn, activates the CNS to orchestrate negative-feedback mechanisms that keep the immune response in check. Disruption of these interactions has been associated with a number of syndromes including inflammatory, autoimmune, and cardiovascular diseases, metabolic and psychiatric disorders, and the development of shock. The hypothalamic-pituitary-gonadal axis also plays an important part in regulating immunity through the secretion of sex hormones. Although numerous studies have established a role for immunomodulation by estrogen and testosterone, the role of progesterone is less well understood. Progesterone is crucial for reproductive organ development and maintenance of pregnancy, and more recent studies have clearly shown its role as an important immune regulator. The main focus of this review will be about the role of steroid hormones, specifically glucocorticoids and progesterone, in inflammatory responses and infectious diseases and how dysregulation of their actions may contribute to development of autoimmune and inflammatory disease.