Using passive extraction of real-world data from eConsent, electronic patient reported outcomes (ePRO) and electronic health record (EHR) data loaded to an electronic data capture (EDC) system for a multi-center, prospective, observational study in diabetic patients.

As clinical trial complexity has increased over the past decade, using electronic methods to simplify recruitment and data management have been investigated. In this study, the Optum Digital Research Network (DRN) has demonstrated the use of electronic source (eSource) data to ease subject identification, recruitment burden, and used data extracted from electronic health records (EHR) to load to an electronic data capture (EDC) system. This study utilized electronic Informed Consent, electronic patient reported outcomes (SF-12) and included three sites using 3 different EHR systems. Patients with type 2 diabetes with an HbA1c ≥ 7.0% treated with metformin monotherapy were recruited. Endpoints consisted of changes in HbA1c, medications, and quality of life measures over 12-weeks of study participation using data from the subjects' eSources listed above. The study began in June of 2020 and the last patient last visit occurred in January of 2021. Forty-eight participants were consented and enrolled. HbA1c was repeated for 33 and ePRO was obtained from all subjects at baseline and 28 at 12-week follow-up. Using eSource data eliminated transcription errors. Medication changes, healthcare encounters and lab results were identified when they occurred in standard clinical practice from the EHR systems. Minimal data transformation and normalization was required. Data for this observational trial where clinical outcomes are available using lab results, diagnoses, and encounters may be achieved via direct access to eSources. This methodology was successful and could be expanded for larger trials and will significantly reduce staff effort and exemplified clinical research as a care option.

Vitamin D Deficiency and Air Pollution Exacerbate COVID-19 Through Suppression of Antiviral Peptide LL37.

Vitamin D deficiency and insufficiency (VDD) are widely recognized as risk factors for respiratory tract infections. Vitamin D influences expression of many genes with well-established relevance to airway infections and relevant to immune system function. Recently, VDD has been shown to be a risk factor for acquisition and severity of COVID-19. Thus, treating VDD presents a safe and inexpensive opportunity for modulating the severity of the disease. VDD is common in those over 60 years of age, many with co-morbid conditions and in people with skin pigmentation sufficient to reduce synthesis of vitamin D. Exposure to fine particulate air pollution is also associated with worse outcomes from COVID19. Vitamin D stimulates transcription of cathelicidin which is cleaved to generate LL37. LL37 is an innate antimicrobial with demonstrated activity against a wide range of microbes including envelope viruses. LL37 also modulates cytokine signaling at the site of infections. Fine particles in air pollution can interfere with LL37 destruction of viruses and may reduce effective immune signaling modulation by LL37. While vitamin D influences transcription of many immune related genes, the weakened antimicrobial response of those with VDD against SARS-CoV-2 may be in part due to reduced LL37. Conclusion: Vitamin D plays an important role reducing the impact of viral lung disease processes. VDD is an acknowledged public health threat that warrants population-wide action to reduce COVID-19 morbidity and mortality. While vitamin D influences transcription of many immune related genes, the weakened antimicrobial response of those with VDD against SARS-CoV-2 may be in part due to reduced LL37. Action is needed to address COVID-19 associated risks of air pollution from industry, transportation, domestic sources and from primary and second hand tobacco smoke.

Digital Delivery of Meditative Movement Training Improved Health of Cigarette-Smoke-Exposed Subjects.

Many FA who flew prior to the ban on smoking in commercial aircraft exhibit an unusual pattern of long-term pulmonary dysfunction. This randomized controlled study tested the hypothesis that digitally delivered meditative movement (MM) training improves chronic obstructive pulmonary disease (COPD)-related symptoms in flight attendants (FA) who were exposed to second-hand cigarette smoke (SHCS) while flying. Phase I of this two-phase clinical trial was a single-arm non-randomized pilot study that developed and tested methods for MM intervention; we now report on Phase II, a randomized controlled trial comparing MM to a control group of similar FA receiving health education (HE) videos. Primary outcomes were the 6-min walk test and blood levels of high sensitivity C-reactive protein (hs-CRP). Pulmonary, cardiovascular, autonomic and affective measures were also taken. There were significant improvements in the 6-min walk test, the Multidimensional Assessment of Interoceptive Awareness (MAIA) score, and the COPD Assessment Test. Non-significant trends were observed for increased dehydroepiandrosterone sulfate (DHEAS) levels, decreased anxiety scores and reduced blood hs-CRP levels, and increased peak expiratory flow (PEF). In a Survey Monkey questionnaire, 81% of participants who completed pre and post-testing expressed mild to strong positive opinions of the study contents, delivery, or impact, while 16% expressed mild negative opinions. Over the course of the year including the study, participant adoption of the MM practices showed a significant and moderately large correlation with overall health improvement; Pearson's R = 0.62, p < 0.005. These results support the hypothesized benefits of video-based MM training for this population. No adverse effects were reported. Clinical Trial Registration: www.ClinicalTrials.gov, identifier: NCT02612389.

Accreditation Standard Guideline Initiative for Tai Chi and Qigong Instructors and Training Institutions.

Evidence of the health and wellbeing benefits of Tai Chi and Qigong (TQ) have emerged in the past two decades, but TQ is underutilized in modern health care in Western countries due to lack of promotion and the availability of professionally qualified TQ instructors. To date, there are no government regulations for TQ instructors or for training institutions in China and Western countries, even though TQ is considered to be a part of Traditional Chinese medicine that has the potential to manage many chronic diseases. Based on an integrative health care approach, the accreditation standard guideline initiative for TQ instructors and training institutions was developed in collaboration with health professionals, integrative medicine academics, Tai Chi and Qigong master instructors and consumers including public safety officers from several countries, such as Australia, Canada, China, Germany, Italy, Korea, Sweden and USA. In this paper, the rationale for organizing the Medical Tai Chi and Qigong Association (MTQA) is discussed and the accreditation standard guideline for TQ instructors and training institutions developed by the committee members of MTQA is presented. The MTQA acknowledges that the proposed guidelines are broad, so that the diversity of TQ instructors and training institutions can be integrated with recognition that these guidelines can be developed with further refinement. Additionally, these guidelines face challenges in understanding the complexity of TQ associated with different principles, philosophies and schools of thought. Nonetheless, these guidelines represent a necessary first step as primary resource to serve and guide health care professionals and consumers, as well as the TQ community.

Effectiveness of a Novel Qigong Meditative Movement Practice for Impaired Health in Flight Attendants Exposed to Second-Hand Cigarette Smoke.

This single-arm non-randomized pilot study explores an intervention to improve the health of flight attendants (FA) exposed to second-hand cigarette smoke prior to the smoking ban on commercial airlines. This group exhibits an unusual pattern of long-term pulmonary dysfunction. We report on Phase I of a two-phase clinical trial; the second Phase will be a randomized controlled trial testing digital delivery of the intervention. Subjects were recruited in the Northeastern US; testing and intervention were administered in 4 major cities. The intervention involved 12 h of training in Meditative Movement practices. Based on recent research on the effects of nicotine on fear learning, and the influence of the autonomic nervous system on immune function, our hypothesis was that this training would improve autonomic function and thus benefit a range of health measures. Primary outcomes were the 6-min walk test and blood levels of C-reactive protein. Pulmonary, cardiovascular, autonomic, and affective measures were also taken. Fourteen participants completed the training and post-testing. There was a 53% decrease in high sensitivity C-Reactive Protein (p ≤ 0.05), a 7% reduction in systolic blood pressure (p ≤ 0.05), a 13% increase in the 6-min walk test (p ≤ 0.005), and significant positive changes in several other outcomes. These results tend to confirm the hypothesized benefits of MM training for this population, and indicate that autonomic function may be important in the etiology and treatment of their symptoms. No adverse effects were reported. This trial is registered at ClinicalTrials.gov (https://clinicaltrials.gov/ct2/show/NCT02612389/), and is supported by a grant from the Flight Attendant Medical Research Institute (FAMRI).

Meditative Movement as a Treatment for Pulmonary Dysfunction in Flight Attendants Exposed to Second-Hand Cigarette Smoke: Study Protocol for a Randomized Trial.

A study protocol is presented for the investigation of meditative movement (MM) as a treatment for pulmonary dysfunction in flight attendants (FA) who were exposed to second-hand cigarette smoke while flying before the smoking ban. The study will have three parts, some of which will run concurrently. The first is a data gathering and screening phase, which will gather data on pulmonary and other aspects of the health of FA, and will also serve to screen participants for the other phases. Second is an exercise selection phase, in which a variety of MM exercises will be taught, over a 16-week period, to a cohort of 20 FA. A subset of these exercises will be selected on the basis of participant feedback on effectiveness and compliance. Third is a 52-week randomized controlled trial to evaluate the effectiveness of a digitally delivered form of the previously selected exercises on a group of 20 FA, as compared with an attention control group. Outcome measures to be used in all three parts of the study include the 6-min walk test as a primary measure, as well as a range of biomarkers, tests, and questionnaires documenting hormonal, cardio-respiratory, autonomic, and affective state. This study is registered at ClinicalTrials.gov. Identifier: NCT02612389.

The preparatory set: a novel approach to understanding stress, trauma, and the bodymind therapies.

Basic to all motile life is a differential approach/avoid response to perceived features of environment. The stages of response are initial reflexive noticing and orienting to the stimulus, preparation, and execution of response. Preparation involves a coordination of many aspects of the organism: muscle tone, posture, breathing, autonomic functions, motivational/emotional state, attentional orientation, and expectations. The organism organizes itself in relation to the challenge. We propose to call this the "preparatory set" (PS). We suggest that the concept of the PS can offer a more nuanced and flexible perspective on the stress response than do current theories. We also hypothesize that the mechanisms of body-mind therapeutic and educational systems (BTES) can be understood through the PS framework. We suggest that the BTES, including meditative movement, meditation, somatic education, and the body-oriented psychotherapies, are approaches that use interventions on the PS to remedy stress and trauma. We discuss how the PS can be adaptive or maladaptive, how BTES interventions may restore adaptive PS, and how these concepts offer a broader and more flexible view of the phenomena of stress and trauma. We offer supportive evidence for our hypotheses, and suggest directions for future research. We believe that the PS framework will point to ways of improving the management of stress and trauma, and that it will suggest directions of research into the mechanisms of action of BTES.

Corrigendum: Somatic Experiencing: using interoception and proprioception as core elements of trauma therapy.

[This corrects the article on p. 93 in vol. 6, PMID: 25699005.].

Somatic experiencing: using interoception and proprioception as core elements of trauma therapy.

Here we present a theory of human trauma and chronic stress, based on the practice of Somatic Experiencing(®) (SE), a form of trauma therapy that emphasizes guiding the client's attention to interoceptive, kinesthetic, and proprioceptive experience. SE™ claims that this style of inner attention, in addition to the use of kinesthetic and interoceptive imagery, can lead to the resolution of symptoms resulting from chronic and traumatic stress. This is accomplished through the completion of thwarted, biologically based, self-protective and defensive responses, and the discharge and regulation of excess autonomic arousal. We present this theory through a composite case study of SE treatment; based on this example, we offer a possible neurophysiological rationale for the mechanisms involved, including a theory of trauma and chronic stress as a functional dysregulation of the complex dynamical system formed by the subcortical autonomic, limbic, motor and arousal systems, which we term the core response network (CRN). We demonstrate how the methods of SE help restore functionality to the CRN, and we emphasize the importance of taking into account the instinctive, bodily based protective reactions when dealing with stress and trauma, as well as the effectiveness of using attention to interoceptive, proprioceptive and kinesthetic sensation as a therapeutic tool. Finally, we point out that SE and similar somatic approaches offer a supplement to cognitive and exposure therapies, and that mechanisms similar to those discussed in the paper may also be involved in the benefits of meditation and other somatic practices.

Activation of poly(adenosine diphosphate-ribose) polymerase in mouse tumors treated by photodynamic therapy.

Poly(adenosine diphosphate-ribose) polymerase (PARP) has recently been characterized as a key regulator of cell death-survival transcriptional programs associated with stress and inflammation. Possible participation of this enzyme in the response of tumors to photodynamic therapy (PDT) was investigated in this study. Immunohistochemical analysis of mouse FsaR tumors treated by PDT based on photosensitizers Photofrin or 5,10,15,20-tetra-(m-hydroxyphenyl)chlorine (mTHPC) revealed a strong positive staining for PARP product poly(ADP-ribose) at 30 min and 1 h after PDT, respectively, and even more intense positivity at 2 h after PDT with both photosensitizers. Flow cytometry-based examination showed the induction of poly-ADP-ribosylation in FsaR tumors at 30 min after PDT, with a trend for a further increase in the intensity by 2 h after PDT in both cancer cells and tumor-associated leukocytes. In FsaR cells treated in vitro by mTHPC-based PDT, flow cytometric analysis indicated that the activation of PARP concentrated in cells undergoing apoptosis and reached a maximum by 30 min after PDT. The administration of PARP inhibitors, 3-aminobenzamide or 1,5-isoquinolinediol, to FsaR tumor-bearing mice before PDT light treatment increased the resistance of these tumors to PDT. PARP appears to control the balance between apoptotic and necrotic cell death in PDT-treated tumors and regulate the progression of PDT-induced inflammatory or innate immune response.

Movement-based embodied contemplative practices: definitions and paradigms.

Over the past decades, cognitive neuroscience has witnessed a shift from predominantly disembodied and computational views of the mind, to more embodied and situated views of the mind. These postulate that mental functions cannot be fully understood without reference to the physical body and the environment in which they are experienced. Within the field of contemplative science, the directing of attention to bodily sensations has so far mainly been studied in the context of seated meditation and mindfulness practices. However, the cultivation of interoceptive, proprioceptive and kinesthetic awareness is also said to lie at the core of many movement-based contemplative practices such as Yoga, Qigong, and Tai Chi. In addition, it likely plays a key role in the efficacy of modern somatic therapeutic techniques such as the Feldenkrais Method and the Alexander Technique. In the current paper we examine how these practices are grounded in the concepts of embodiment, movement and contemplation, as we look at them primarily through the lens of an enactive approach to cognition. Throughout, we point to a series of challenges that arise when Western scientists study practices that are based on a non-dualistic view of mind and body.

Meditative movement for depression and anxiety.

This review focuses on Meditative Movement (MM) and its effects on anxiety, depression, and other affective states. MM is a term identifying forms of exercise that use movement in conjunction with meditative attention to body sensations, including proprioception, interoception, and kinesthesis. MM includes the traditional Chinese methods of Qigong (Chi Kung) and Taijiquan (Tai Chi), some forms of Yoga, and other Asian practices, as well as Western Somatic practices; however this review focuses primarily on Qigong and Taijiquan. We clarify the differences between MM and conventional exercise, present descriptions of several of the key methodologies of MM, and suggest how research into these practices may be approached in a systematic way. We also present evidence for possible mechanisms of the effects of MM on affective states, including the roles of posture, rhythm, coherent breathing, and the involvement of specific cortical and subcortical structures. We survey research outcomes summarized in reviews published since 2007. Results suggest that MM may be at least as effective as conventional exercise or other interventions in ameliorating anxiety and depression; however, study quality is generally poor and there are many confounding factors. This makes it difficult to draw definitive conclusions at this time. We suggest, however, that more research is warranted, and we offer specific suggestions for ensuring high-quality and productive future studies.

Increase of sensitivity of sputum cytology using high-resolution image cytometry: field study results.

Lung cancer remains the leading cause of cancer deaths in the developed world. There is no widely accepted method to screen for this cancer. The most commonly used method remains conventional sputum cytology, but this method is hampered by low sensitivity. We tested the hypothesis that sensitivity of sputum cytology for early lung cancer can be greatly improved by using image analysis of sputum cells, at a modest reduction of specificity. The study was double-blinded and used sputum samples from subjects with well-characterized clinical diagnoses. There were 177 cancers, 98 dysplasias, and 558 normals. The study samples were separated into two independent sets: training set and test set. Sputum samples were collected prospectively from subjects with a high probability of having lung cancer. Seven institutions from five countries participated in the study. All subjects had complete clinical diagnoses which included, as a minimum, negative chest x-rays for all negative cancers, while all cancers had confirmed tissue pathology. Samples were prepared according to the Saccomanno method. For conventional cytology, slides were stained using Papanicolaou stain. For image analysis, slides were stained using a DNA-specific (Feulgen-Thionin) stain. An automated, high-resolution image cytometer was used for measurements. At 90% specificity, sensitivity of 60% can be achieved for adenocarcinoma, compared to only 14% sensitivity of conventional cytology (at 99% specificity). Similarly, 45% sensitivity at 90% specificity can be reached for stages 0 and I lung cancer, compared to only 14% (at 99% specificity) using conventional cytology.Cytometry combined with conventional cytology shows an increase in sensitivity to early-stage cancer and to adenocarcinomas compared to conventional cytology alone. While the results are encouraging, the sensitivity to detect early lung cancer should be further improved to 70-80% at 90-95% specificity before this test can be considered for screening of high-risk individuals for lung cancer. Cytometry (Clin. Cytometry) 50:168-176, 2002.