Integrated multicomponent interventions to support healthy aging of the whole person.

Healthy aging is an integrated "whole person" process that involves an individual's biology, behavior, and social/physical environment. With the recent development of antiaging drugs, careful consideration of the respective roles of pharmacologic and nonpharmacologic approaches to both health and aging is in order. Recent advances in understanding the cellular and molecular mechanisms of aging are providing new measures that can be used as clinical outcomes in studying the impact of antiaging interventions in humans. This paper outlines the strategic interest of the National Center for Complementary and Integrative Health (NCCIH) in supporting the development, testing, and implementation of effective, scalable, and integrated multicomponent interventions to support healthy aging of the whole person.

Effect of stretching on inflammation in a subcutaneous carrageenan mouse model analyzed at single-cell resolution.

Understanding the factors that influence the biological response to inflammation is crucial, due to its involvement in physiological and pathological processes, including tissue repair/healing, cancer, infections, and autoimmune diseases. We have previously demonstrated that in vivo stretching can reduce inflammation and increase local pro-resolving lipid mediators in rats, suggesting a direct mechanical effect on inflammation resolution. Here we aimed to explore further the effects of stretching at the cellular/molecular level in a mouse subcutaneous carrageenan-inflammation model. Stretching for 10 min twice a day reduced inflammation, increased the production of pro-resolving mediator pathway intermediate 17-HDHA at 48 h postcarrageenan injection, and decreased both pro-resolving and pro-inflammatory mediators (e.g., PGE2 and PGD2 ) at 96 h. Single-cell RNA sequencing analysis of inflammatory lesions at 96 h showed that stretching increased the expression of both pro-inflammatory (Nos2) and pro-resolution (Arg1) genes in M1 and M2 macrophages at 96 h. An intercellular communication analysis predicted specific ligand-receptor interactions orchestrated by neutrophils and M2a macrophages, suggesting a continuous neutrophil presence recruiting immune cells such as activated macrophages to contain the antigen while promoting resolution and preserving tissue homeostasis.

Total Force Fitness: Making Holistic, Integrated Whole-Person Research a DoD Priority.

Total Force Fitness (TFF) was conceived as a holistic framework for building and sustaining Human Performance Optimization for Warfighters and their families. As such, TFF research must also be holistic in nature. During the research breakout, group barriers and challenges to TFF research were discussed, and critical research focus areas were prioritized. The top approaches discussed were (1) using big data to identify best practices and health trajectories; (2) applying community-based participatory research principles to military units; (3) focusing on "Whole-Person," integrative research (physical, behavioral, spiritual, and biological) across the Department of Defense; and, finally, (4) prioritizing key opportunities to advance TFF across the active duty and Reserve/Guard enterprises and their families. The research group noted that coordinated action would be needed to move the prioritized agenda forward. Finally, translating research into action is essential because TFF is a way of honoring our service members as whole persons with careers, goals, and families.

Complementary and integrative health therapies in whole person resilience research.

Complementary and integrative health approaches can improve health and well-being, as well as play an important role in disease prevention. The concept of whole person health builds on these concepts by empowering individuals, families, communities, and populations to improve their health in multiple interconnected domains: biological, behavioural, social, and environmental. Research on whole person health involves studies of interconnected biological systems and complex approaches to prevention and treatment. Some of these approaches may involve methods of diagnosis and therapy that differ from those used in conventional Western medicine. Of growing interest is how complementary, integrative, and whole person health approaches contribute to resilience. This brief commentary describes an integrated framework for mapping the connections between various complementary and integrative health therapeutic inputs onto aspects of resilience, including the ability to resist, recover (partially or fully), adapt, and/or grow in response to a following a stressor. The authors present selected examples of research studies supported by the National Institutes of Health that test whether complementary and integrative health approaches can promote some aspect of resilience. We conclude with a discussion of the challenges and opportunities in incorporating the study of resilience in complementary, integrative, and whole person health research.

Making Connections to Improve Health Outcomes.

This issue of Global Advances in Health and Medicine sends a vital message about the importance of whole person health. Whole person health rests on the idea that our health involves multiple interconnected factors across physiological systems, as well as biological, behavioral, social, and environmental domains. The urgency of better understanding whole person health is highlighted by the current global health crisis. Yet, biomedical research often favors a reductionist approach. The current emphasis on diseases or single organ systems can fall short when it comes to addressing the interconnected factors that contribute to worse health outcomes. This, coupled with a fragmented health care delivery system, contributes to the challenges that patients face every day in becoming healthier. As part of the U.S. National Institutes of Health, our role at the National Center for Complementary and Integrative Health (NCCIH) is to foster research in this field. NCCIH's twenty years of research has built a body of knowledge that has established a clear path forward for exploring whole person health in the coming years. Within the framework of our strategic plan, NCCIH is working to build research methods for studying whole person health and explore how this understanding of health can transform the way complementary and integrative health is perceived and implemented within the wider health care delivery system.The collection of papers highlighted in this month's issue of Global Advances in Health and Medicine sends an important and encouraging signal about the efforts being made to deliver health care in a way that recognizes the importance of whole person health. Each of these studies provides new insights on how stakeholders might approach transforming the delivery of health care, integrating approaches that can improve health outcomes for people.

Fascia Mobility, Proprioception, and Myofascial Pain.

The network of fasciae is an important part of the musculoskeletal system that is often overlooked. Fascia mobility, especially along shear planes separating muscles, is critical for musculoskeletal function and may play an important, but little studied, role in proprioception. Fasciae, especially the deep epimysium and aponeuroses, have recently been recognized as highly innervated with small diameter fibers that can transmit nociceptive signals, especially in the presence of inflammation. Patients with connective tissue hyper- and hypo-mobility disorders suffer in large number from musculoskeletal pain, and many have abnormal proprioception. The relationships among fascia mobility, proprioception, and myofascial pain are largely unstudied, but a better understanding of these areas could result in improved care for many patients with musculoskeletal pain.

Reconnecting the Brain With the Rest of the Body in Musculoskeletal Pain Research.

A challenge in understanding chronic musculoskeletal pain is that research is often siloed between neuroscience, physical therapy/rehabilitation, orthopedics, and rheumatology which focus respectively on 1) neurally mediated effects on pain processes, 2) behavior and muscle activity, 3) tissue structure, and 4) inflammatory processes. Although these disciplines individually study important aspects of pain, there is a need for more cross-disciplinary research that can bridge between them. Identifying the gaps in knowledge is important to understand the whole body, especially at the interfaces between the silos-between brain function and behavior, between behavior and tissue structure, between musculoskeletal and immune systems, and between peripheral tissues and the nervous system. Research on "mind and body" practices can bridge across these silos and encourage a "whole person" approach to better understand musculoskeletal pain by bringing together the brain and the rest of the body. PERSPECTIVE: Research on chronic musculoskeletal pain is limited by significant knowledge gaps. To be fully integrated, musculoskeletal pain research will need to bridge across tissues, anatomical areas, and body systems. Research on mind and body approaches encourages a "whole person" approach to better understand musculoskeletal pain.

The Emerging Science of Interoception: Sensing, Integrating, Interpreting, and Regulating Signals within the Self.

Interoception refers to the representation of the internal states of an organism, and includes the processes by which it senses, interprets, integrates, and regulates signals from within itself. This review presents a unified research framework and attempts to offer definitions for key terms to describe the processes involved in interoception. We elaborate on these definitions through illustrative research findings, and provide brief overviews of central aspects of interoception, including the anatomy and function of neural and non-neural pathways, diseases and disorders, manipulations and interventions, and predictive modeling. We conclude with discussions about major research gaps and challenges.

Establishment of a Novel Porcine Model to Study the Impact of Active Stretching on a Local Carrageenan-Induced Inflammation.

OBJECTIVE: Active stretching of the body is integral to complementary mind-body therapies such as yoga, as well as physical therapy, yet the biologic mechanisms underlying its therapeutic effects remain largely unknown. A previous study showed the impact of active stretching on inflammatory processes in rats. The present study tested the feasibility of using a porcine model, with a closer resemblance to human anatomy, to study the effects of active stretching in the resolution of localized inflammation. DESIGN: A total of 12 pigs were trained to stretch before subcutaneous bilateral Carrageenan injection in the back at the L3 vertebrae, 2 cm from the midline. Animals were randomized to no-stretch or stretch, twice a day for 5 mins over 48 hrs. Animals were euthanized for tissue collection 48 hrs postinjection. RESULTS: The procedure was well tolerated by the pigs. On average, lesion area was significantly smaller by 36% in the stretch group compared with the no-stretch group (P = 0.03). CONCLUSION: This porcine model shows promise for studying the impact of active stretching on inflammation-resolution mechanisms. These results are relevant to understanding the stretching-related therapeutic mechanisms of mind-body therapies. Future studies with larger samples are warranted.

Identifying Stress Landscapes in Boston Neighborhoods.

BACKGROUND: Chronic stress plays a role in the development of health disparities. However, the relationship between neighborhood stressors and stress-related health problems and behaviors is unknown. In the city of Boston, Massachusetts, 3 neighborhoods, while within a 3 mile radius, have widely divergent life expectancies. This work aims to investigate and compare perceived neighborhood-level stressors, stress-related negative behaviors, and stress-related health problems in these neighborhoods. METHODS: Three hundred twenty-six participants were surveyed from the neighborhoods. Participants were asked to rate (1) 27 neighborhood stressors, (2) 16 stress-related negative behaviors, and (3) 13 stress-related health problems using a 1 to 5 Likert-type scale. Differences in responses between neighborhoods were analyzed using Kruskal-Wallis and χ2 tests. RESULTS: The highest neighborhood stressors overall were related to finance, unequal treatment, and unsafe bike/pedestrian access. The highest stress-related health problems were related to substance abuse and obesity, and the largest stress-related behaviors were related to poor diet, intolerance, and aggressive driving. There were significant differences across neighborhoods (P < .05) for 18 of the 27 neighborhood stressors, 8 of the 10 stress-related health problems, and 12 of the 15 stress-related behaviors. CONCLUSIONS: There is marked contrast in stress landscapes between the 3 neighborhoods in Boston despite their geographical proximity. This finding potentially serves as an explanation for the drastic differences in health outcomes, even though these neighborhoods are equidistant from academic medical centers. Strategies for improving the health of individuals should incorporate the unique stressors at the neighborhood level. Further research is needed to investigate how specifically neighborhood stressors influence the health of residents, thereby informing what policy interventions might be useful.

What Is the Point? The Problem with Acupuncture Research That No One Wants to Talk About.

Despite having made substantial progress in academic rigor over the past decades, acupuncture research has been the focus of long-standing and persistent attacks by skeptics. One recurring theme of critics is that the concept of acupuncture points has no scientific validity. Meanwhile, the subject of whether-or-not acupuncture points "exist" has been given too little attention within the acupuncture research community. In this article, we argue that failure to use clear terminology and rigorously investigate the subject of acupuncture points has hindered the growing legitimacy of acupuncture as an evidence-based therapy. We propose that a coordinated effort is needed to improve the use of terminology related to acupuncture points, combined with rigorous investigation of their "specificity" and possible biological basis.

Flexibility and strength training in asthma: A pilot study.

OBJECTIVE: Although less is known about musculoskeletal factors that may contribute to asthma symptoms, body-based treatments addressing movement restrictions of the chest and shoulders may be a useful adjunct to asthma pharmacotherapy. In this pilot study, we compared asthma symptoms, pulmonary function tests, and medication use before and after a course of resistance flexibility and strength training (RFST) treatments in human subjects with asthma. METHODS: Patients with asthma (n = 10; mean age 23 years) completed questionnaires (Asthma Control Questionnaire (ACQ), Asthma Quality of Life Questionnaire (AQLQ), Asthma Control Test (ACT)), spirometry, chest wall excursion, and shoulder range of motion (ROM) before and after a series of four RFST treatments over 47 ± 21 days. Each treatment consisted of a one-hour session involving eccentric stretching of the arm, shoulder, and chest while lying in a supine position. RESULTS: Significant clinical improvement was observed for mean ACQ scores from pre- to post-treatment (mean decrease 0.73, 95% CI 0.26-1.09, Cohen d = 2.25, p =.0014). No significant improvement was observed in the ACT, AQLQ, or spirometry, although inhaler use decreased for half of the subjects and did not change for the remaining subjects (i.e. none increased). Chest wall excursion and all ROM tests trended toward improvement, but was only statistically significant (p <.05) for the arm raise in the frontal plane. CONCLUSION: RFST may be a beneficial, nonpharmacological method to decrease asthma symptoms. Future studies should be conducted involving a larger sample size, longer intervention time, control group, and blood collection to test inflammatory mediators.

Effect of Stretching on Thoracolumbar Fascia Injury and Movement Restriction in a Porcine Model.

OBJECTIVE: Stretching of fascia is an important component of manual and movement therapies. We previously showed that in pigs, a unilateral thoracolumbar fascia injury combined with movement restriction (hobble) produced contralateral loss of fascia mobility (shear strain during passive trunk flexion measured with ultrasound) similar to findings in human subjects with chronic low back pain. We now tested whether such abnormalities could be reversed by removing the hobble with or without daily stretching for 1 mo. DESIGN: Thirty pigs were randomized to control, injury, or injury + hobble for 8 wks. The hobble restricted hip extension ipsilateral to the injury. At week 8, the injury + hobble group was subdivided into continued hobble, removed hobble, and removed hobble + stretching (passively extending the hip for 10 min daily). RESULTS: Removing hobbles restored normal gait speed but did not restore fascia mobility. Daily passive stretching was not superior to removing hobbles, as there was no significant improvement in fascia mobility with either treatment group (removed hobble or stretching). CONCLUSIONS: Reduced fascia mobility in response to injury and movement restriction worsens over time and persists even when movement is restored. Reversing fascia abnormalities may require either longer than 1 mo or a different treatment "dose" or modality.

The National Cancer Institute's Conference on Acupuncture for Symptom Management in Oncology: State of the Science, Evidence, and Research Gaps.

The Division of Cancer Treatment and Diagnosis, Office of Cancer Complementary and Alternative Medicine, at the National Cancer Institute (NCI) held a symposium on "Acupuncture for Cancer Symptom Management" on June 16 and 17, 2016. Invited speakers included 19 scientists and scholars with expertise in acupuncture and cancer research from the United States, Europe, and China. The conference reviewed the NCI's grant funding on acupuncture, analyzed the needs of cancer patients, reviewed safety issues, and assessed both the current scientific evidence and research gaps of acupuncture in oncology care. Researchers and stakeholders presented and discussed basic mechanisms of acupuncture; clinical evidence for specific symptoms; and methodological challenges such as placebo effects, novel biostatistical methods, patient-reported outcomes, and comparative effectiveness research. This paper, resulting from the conference, summarizes both the current state of the science and clinical evidence of oncology acupuncture, identifies key scientific gaps, and makes recommendations for future research to increase understanding of both the mechanisms and effects of acupuncture for cancer symptom management.

Stretching Reduces Skin Thickness and Improves Subcutaneous Tissue Mobility in a Murine Model of Systemic Sclerosis.

OBJECTIVE: Although physical therapy can help preserve mobility in patients with systemic sclerosis (SSc), stretching has not been used systematically as a treatment to prevent or reverse the disease process. We previously showed in rodent models that stretching promotes the resolution of connective tissue inflammation and reduces new collagen formation after injury. Here, we tested the hypothesis that stretching would impact scleroderma development using a mouse sclerodermatous graft-versus-host disease (sclGvHD) model. METHODS: The model consists in the adoptive transfer (allogeneic) of splenocytes from B10.D2 mice (graft) into Rag2-/- BALB/c hosts (sclGvHD), resulting in skin inflammation followed by fibrosis over 4 weeks. SclGvHD mice and controls were randomized to stretching in vivo for 10 min daily versus no stretching. RESULTS: Weekly ultrasound measurements of skin thickness and subcutaneous tissue mobility in the back (relative tissue displacement during passive trunk motion) successfully captured the different phases of the sclGvHD model. Stretching reduced skin thickness and increased subcutaneous tissue mobility compared to no stretching at week 3. Stretching also reduced the expression of CCL2 and ADAM8 in the skin at week 4, which are two genes known to be upregulated in both murine sclGvHD and the inflammatory subset of human SSc. However, there was no evidence that stretching attenuated inflammation at week 2. CONCLUSION: Daily stretching for 10 min can improve skin thickness and mobility in the absence of any other treatment in the sclGvHD murine model. These pre-clinical results suggest that a systematic investigation of stretching as a therapeutic modality is warranted in patients with SSc.

Connecting (T)issues: How Research in Fascia Biology Can Impact Integrative Oncology.

Complementary and integrative treatments, such as massage, acupuncture, and yoga, are used by increasing numbers of cancer patients to manage symptoms and improve their quality of life. In addition, such treatments may have other important and currently overlooked benefits by reducing tissue stiffness and improving mobility. Recent advances in cancer biology are underscoring the importance of connective tissue in the local tumor environment. Inflammation and fibrosis are well-recognized contributors to cancer, and connective tissue stiffness is emerging as a driving factor in tumor growth. Physical-based therapies have been shown to reduce connective tissue inflammation and fibrosis and thus may have direct beneficial effects on cancer spreading and metastasis. Meanwhile, there is currently little knowledge on potential risks of applying mechanical forces in the vicinity of tumors. Thus, both basic and clinical research are needed to understand the full impact of integrative oncology on cancer biology as well as whole person health. Cancer Res; 76(21); 6159-62. ©2016 AACR.