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ObjectivePeople commonly cope with chronic low back pain (cLBP) by ignoring and distraction. Can mindful interoceptive exposure to the pain sensation itself and its phenomenological components be an alternative approach?MethodsSingle-arm feasibility study in patients with cLBP using a 2-minute attention exercise guided by a smartphone app several times per day over 8 weeks. We assessed feasibility, pre/post pain, function, and psychological parameters using mixed methods: standard questionnaires, ecological momentary assessment, and exit interviews that included micro-phenomenology technique and subsequent reflexive thematic qualitative analysis.ResultsWe enrolled 31 participants, mostly female, mean age 48, the majority had pain for >5 years; 29 completed. Mean pain intensity [0-10] improved from 4.8 ±1.7 to 3.1 ±1.9 (p < .0001); mean PEG scores (intensity and interference with daily life; range 0-30) improved from 13.7 ±6.2 to 8.4 ±6.6 (p < .0001); pain impact (9 items incl physical function) 22.3 ±8.7 to 19.7 ±8.1 (p = .0010). Twenty-one of 29 improved PEG score ≥30%. There were significant improvements in PCS Rumination and MAIA Not-Worrying. Participants became aware of their usual habit of avoidance and the challenge of and resistance to focusing on pain. They were surprised how pain sensations varied over time, and that pain intensity and the threat value of pain could diminish by focusing on it. They described a variety of 3D pain shapes (e.g., football, pool ball, rod, nail, brick, stars) with a range of colors, transparency, temperature, and density that for some changed with mindful attention. Most struggled to find appropriate words for sensory awareness and attention regulation and found that the threat value of their pain diminished.ConclusionsMindful interoceptive exposure to the sensations of their cLBP using a 2-minute attention exercise with a phone app-rather than ignoring and distracting from it-may be a beneficial intervention for cLBP.Trial registrationClinicalTrials.gov #NCT06186193.

IntroductionChronic low back pain (cLBP) poses significant challenges, often addressed through avoidance or distraction. Emerging evidence suggests that mind-body interventions, like our novel Mind Your Pain (MyP) smartphone mobile application, may offer relief. We conducted a single-arm, mixed-methods neuroimaging study to assess the degree to which treatment response to our 8-week intervention, as measured by the reduction in the Pain, Enjoyment of Life and General Activity Scale (PEG), was associated with enhanced pain-related insula activation over time.MethodsTwenty-nine individuals with cLBP completed patient-reported assessments, qualitative sensory testing (QST) measures, and neuroimaging pre- and post-MyP. Functional MRI data during experimental heat pain on the left forearm were collected and analyzed, comparing responders (≥50% reduction in PEG scores) and non-responders.ResultsMyP led to significant decreases in PEG scores overall. Furthermore, MyP responders exhibited increased pain-related activation in key brain regions, including the contralateral posterior insula, bilateral ventral anterior insula, ventral anterior cingulate, dorsolateral prefrontal cortex, and nucleus accumbens. Although baseline behavioral and sensory measures did not differ between the two responder groups, baseline neural differences related to the impact of the endogenous back pain were observed.DiscussionMyP appears to modify pain response and underlying neural circuitry, suggesting neural changes in interoception may serve as biomarkers for mind-body interventions in cLBP. This study highlights the potential of MyP as a novel approach for cLBP management, warranting further investigation.

INTRODUCTION: There are few widely-available, evidence-based options to support quality of life (QOL) for people living with Alzheimers disease and related dementias. METHODS: We performed a randomized, controlled trial with a Waitlist control group to determine whether an online, livestream, mind-body, group movement program (Moving Together, 1 hour, 2 days/week, 12 weeks) improves QOL in people with cognitive impairment (PWCI) or care partners (CPs) and explore mechanisms of action. The primary outcome for both participants was self-reported QOL. Secondary outcomes and potential mediators included mobility, isolation, well-being, cognitive function, and sleep in PWCI and burden, positive emotions, caregiver self-efficacy, stress management, and sleep in CPs. Blinded assessors collected outcome data at baseline, 12, and 24 weeks. We assessed adverse events including falls through monthly check-in surveys and collected qualitative data through evaluation surveys. Intention-to-treat analyses used linear mixed models to compare mean change over time between groups and calculated standardized effect sizes (ESs). RESULTS: Ninety-seven dyads enrolled (PWCI: age 76 ± 11 years, 43% female, 80% non-Hispanic White; CPs: age 66 ± 12 years, 78% female, 71% non-Hispanic White); 15% withdrew before 12 weeks and 22% before 24 weeks. PWCI self-reported significantly better QOL from baseline to 12 weeks in the Moving Together group compared to the Waitlist group (ES = 0.474, p = 0.048) and CPs self-reported improved ability to manage stress (ES = 0.484, p = 0.021). Improvements in participant self-reported QOL were mediated by improvements in their self-reported well-being and CP-reported ability to manage stress. Results were similar when the Waitlist group participated in the program (QOL ES = 0.663, p = 0.006; stress management ES = 0.742, p = 0.002) and were supported by qualitative data. Exploratory analyses suggested possible fall reduction in PWCI. There were no study-related serious adverse events. DISCUSSION: Online programs such as Moving Together offer a scalable strategy for supporting high QOL for PWCI and helping CPs manage stress. TRIAL REGISTRATION: ClinicalTrials.gov NCT04621448. HIGHLIGHTS: The approval of new medications that slow cognitive decline in people living with Alzheimers disease and related disorders (ADRD) has raised hope and excitement. However, these medications do not appear to impact quality of life, which is often considered by patients and care partners to be the most important outcome.In this randomized clinical trial, we found that an evidence-based, online, livestream, mind-body, group movement program significantly and meaningfully improves self-rated quality of life in people with ADRD and helps care partners manage stress. Mediation analyses revealed that the key drivers of improvements in participants quality of life were improvements in their feelings of well-being and care partners ability to manage stress. Exploratory analyses also suggested a 30% reduction in falls.These results are important because they suggest that an online program, which is available now and can be performed by people from the comfort of home or other location of choice, could be recommended as a complement or alternative to new therapies to help maximize quality of life for people living with ADRD and their care partners.

ObjectiveOne aim of the Back Pain Consortium (BACPAC) Research Program is to develop an integrated model of chronic low back pain that is informed by combined data from translational research and clinical trials. We describe efforts to maximize data harmonization and accessibility to facilitate Consortium-wide analyses.MethodsConsortium-wide working groups established harmonized data elements to be collected in all studies and developed standards for tabular and nontabular data (eg, imaging and omics). The BACPAC Data Portal was developed to facilitate research collaboration across the Consortium.ResultsClinical experts developed the BACPAC Minimum Dataset with required domains and outcome measures to be collected by use of questionnaires across projects. Other nonrequired domain-specific measures are collected by multiple studies. To optimize cross-study analyses, a modified data standard was developed on the basis of the Clinical Data Interchange Standards Consortium Study Data Tabulation Model to harmonize data structures and facilitate integration of baseline characteristics, participant-reported outcomes, chronic low back pain treatments, clinical exam, functional performance, psychosocial characteristics, quantitative sensory testing, imaging, and biomechanical data. Standards to accommodate the unique features of chronic low back pain data were adopted. Research units submit standardized study data to the BACPAC Data Portal, developed as a secure cloud-based central data repository and computing infrastructure for researchers to access and conduct analyses on data collected by or acquired for BACPAC.ConclusionsBACPAC harmonization efforts and data standards serve as an innovative model for data integration that could be used as a framework for other consortia with multiple, decentralized research programs.

The Biobehavioral Working Group of BACPAC was charged to evaluate a range of psychosocial, psychophysical, and behavioral domains relevant to chronic low back pain, and recommend specific assessment tools and procedures to harmonize biobehavioral data collection across the consortium. Primary references and sources for measure selection were the Initiative on Methods, Measurement, and Pain Assessment in Clinical Trials, the Minimum Data Set from the National Institutes of Health (NIH) Research Task Force on Standards for Chronic Low Back Pain, the Patient-Reported Outcomes Measurement Information System, and NeuroQOL. The questionnaire's recommendations supplemented the NIH HEAL Common Data Elements and BACPAC Minimum Data Set. Five domains were identified for inclusion: Pain Characteristics and Qualities; Pain-Related Psychosocial/Behavioral Factors; General Psychosocial Factors; Lifestyle Choices; and Social Determinants of Health/Social Factors. The Working Group identified best practices for required and optional Quantitative Sensory Testing of psychophysical pain processing for use in BACPAC projects.

BackgroundChronic low back pain (cLBP) is a complex with a heterogenous clinical presentation. A better understanding of the factors that contribute to cLBP is needed for accurate diagnosis, optimal treatment, and identification of mechanistic targets for new therapies. The Back Pain Consortium (BACPAC) Research Program provides a unique opportunity in this regard, as it will generate large clinical datasets, including a diverse set of harmonized measurements. The Theoretical Model Working Group was established to guide BACPAC research and to organize new knowledge within a mechanistic framework. This article summarizes the initial work of the Theoretical Model Working Group. It includes a three-stage integration of expert opinion and an umbrella literature review of factors that affect cLBP severity and chronicity.MethodsDuring Stage 1, experts from across BACPAC established a taxonomy for risk and prognostic factors (RPFs) and preliminary graphical depictions. During Stage 2, a separate team conducted a literature review according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines to establish working definitions, associated data elements, and overall strength of evidence for identified RPFs. These were subsequently integrated with expert opinion during Stage 3.ResultsThe majority (∼80%) of RPFs had little strength-of-evidence confidence, whereas seven factors had substantial confidence for either a positive association with cLBP (pain-related anxiety, serum C-reactive protein, diabetes, and anticipatory/compensatory postural adjustments) or no association with cLBP (serum interleukin 1-beta / interleukin 6, transversus muscle morphology/activity, and quantitative sensory testing).ConclusionThis theoretical perspective will evolve over time as BACPAC investigators link empirical results to theory, challenge current ideas of the biopsychosocial model, and use a systems approach to develop tools and algorithms that disentangle the dynamic interactions among cLBP factors.

Abstract Climate variability on centennial timescales has often been linked to internal variability of the Atlantic Meridional Overturning Circulation (AMOC). However, due to the scarceness of suitable paleoclimate proxies and long climate model simulations, large uncertainties remain on the magnitude and physical mechanisms driving centennial‐scale AMOC variability. For these reasons, we perform a systematic multi‐model comparison of centennial‐scale AMOC variability in pre‐industrial control simulations of state‐of‐the‐art global climate models. Six out of nine models in this study exhibit a statistically significant mode of centennial‐scale AMOC variability. Our results show that freshwater exchanges between the Arctic Ocean and the North Atlantic provide a plausible driving mechanism in a subset of models, and that AMOC variability can be amplified by ocean–sea ice feedbacks in the Labrador Sea. The amplifying mechanism is linked to sea ice cover biases, which could provide an observational constraint for centennial‐scale AMOC variability.

IntroductionChronic low back pain (cLBP) poses significant challenges, often addressed through avoidance or distraction. Emerging evidence suggests that mind-body interventions, like our novel Mind Your Pain (MyP) smartphone mobile application, may offer relief. We conducted a single-arm, mixed-methods neuroimaging study to assess the degree to which treatment response to our 8-week intervention, as measured by the reduction in the Pain, Enjoyment of Life and General Activity Scale (PEG), was associated with enhanced pain-related insula activation over time.MethodsTwenty-nine individuals with cLBP completed patient-reported assessments, qualitative sensory testing (QST) measures, and neuroimaging pre- and post-MyP. Functional MRI data during experimental heat pain on the left forearm were collected and analyzed, comparing responders (≥50% reduction in PEG scores) and non-responders.ResultsMyP led to significant decreases in PEG scores overall. Furthermore, MyP responders exhibited increased pain-related activation in key brain regions, including the contralateral posterior insula, bilateral ventral anterior insula, ventral anterior cingulate, dorsolateral prefrontal cortex, and nucleus accumbens. Although baseline behavioral and sensory measures did not differ between the two responder groups, baseline neural differences related to the impact of the endogenous back pain were observed.DiscussionMyP appears to modify pain response and underlying neural circuitry, suggesting neural changes in interoception may serve as biomarkers for mind-body interventions in cLBP. This study highlights the potential of MyP as a novel approach for cLBP management, warranting further investigation.

BACKGROUND: Preventing Loss of Independence through Exercise (PLIÉ) is an in-person group mind-body movement program for people across the spectrum of cognitive decline and care partners (CPs). OBJECTIVE: This study developed and refined an online version called Moving Together and tested feasibility and satisfaction with an online delivery. METHODS: In Phase 1, we used qualitative methods to determine which elements of the in-person program were essential to retain for the online version and adaptations that would be needed to support the user experience. In Phase 2, we created a prototype of the online program and iteratively refined it based on user feedback. In Phase 3, we assessed feasibility of online delivery based on class attendance and program completion; we assessed satisfaction and participant-reported outcomes using a post-program evaluation survey with quantitative and qualitative components. RESULTS: Phase 1 findings from 27 participants (14 PLWD, 13 CPs) revealed three key considerations related to online delivery of PLIÉ: technology use, social connection as a primary motivator, and physical safety concerns. Phase 2 iterative testing among 25 participants (14 PLWD, 11 CPs) resulted in key refinements to program delivery and instructional elements; Phase 3 pilot testing included 39 participants (12 PLWD, 15 CPs, 12 MCI) who attended 75 ± 29% of 24 classes; 77% completed the 12-week program, of whom 96% rated it as excellent or good. Participant-reported outcomes included improvements in social connection, emotional well-being, physical function, cognitive function and present-centered body awareness. PLWD or MCI also reported improvements in self-concept, and CPs reported improvements in caregiving self-efficacy. The primary challenges were related to participant navigation of technology. CONCLUSION: The Moving Together online program is feasible for PLWD or MCI and CPs with participants reporting high satisfaction and positive outcomes across multiple domains. Providing individual technology support is critical for the success of livestreamed, online interventions for dementia.

BackgroundFirefighters experience high levels of physical and mental challenges. Yoga interventions have suggested benefits for firefighters.MethodsThis study reports results from a quality improvement assessment at fire departments with a 10-class yoga program. Main outcome is the total score on the Functional Movement Scale (FMS), an observer-based objective performance measure. A score of at least 14 [range 0-20] is considered as protective against injury. Secondary outcome is the score on the Multidimensional Assessment of Interoceptive Awareness (MAIA) questionnaire, a self-report measure for interoceptive bodily awareness as a parameter for a mechanism of action with yoga. We used descriptive statistics and regression analyses.ResultsBoth total FMS and MAIA scores improved statistically significantly. The strongest performance improvement was seen in trunk stability. The mean FMS score improved from below 14 to 14 and higher indicating a decrease in the risk for injury. Changes in FMS and MAIA did not appear to be correlated.DiscussionDespite the limitation of the study design, the findings support the potential benefits from a yoga program for firefighters.

Abstract Background Complex regional pain syndrome (CRPS) develops after injury and is characterized by disproportionate pain, oedema, and functional loss. CRPS has clinical signs of neuropathy as well as neurogenic inflammation. Here, we asked whether skin biopsies could be used to differentiate the contribution of these two systems to ultimately guide therapy. To this end, the cutaneous sensory system including nerve fibres and the recently described nociceptive Schwann cells as well as the cutaneous immune system were analysed. Methods We systematically deep-phenotyped CRPS patients and immunolabelled glabrous skin biopsies from the affected ipsilateral and non-affected contralateral finger of 19 acute ( 12 months after trauma) CRPS patients as well as 25 sex- and age-matched healthy controls (HC). Murine foot pads harvested one week after sham or chronic constriction injury were immunolabelled to assess intraepidermal Schwann cells. Results Intraepidermal Schwann cells were detected in human skin of the finger—but their density was much lower compared to mice. Acute and chronic CRPS patients suffered from moderate to severe CRPS symptoms and corresponding pain. Most patients had CRPS type I in the warm category. Their cutaneous neuroglial complex was completely unaffected despite sensory plus signs, e.g. allodynia and hyperalgesia. Cutaneous innate sentinel immune cells, e.g. mast cells and Langerhans cells, infiltrated or proliferated ipsilaterally independently of each other—but only in acute CRPS. No additional adaptive immune cells, e.g. T cells and plasma cells, infiltrated the skin. Conclusions Diagnostic skin punch biopsies could be used to diagnose individual pathophysiology in a very heterogenous disease like acute CRPS to guide tailored treatment in the future. Since numbers of inflammatory cells and pain did not necessarily correlate, more in-depth analysis of individual patients is necessary.

Performing interferometry in an optical lattice formed by standing waves of light offers potential advantages over its free-space equivalents since the atoms can be confined and manipulated by the optical potential. We demonstrate such an interferometer in a one-dimensional lattice and show the ability to control the atoms by imaging and reconstructing the wave function at many stages during its cycle. An acceleration signal is applied, and the resulting performance is seen to be close to the optimum possible for the time-space area enclosed according to quantum theory. Our methodology of machine design enables the sensor to be reconfigurable on the fly, and when scaled up, offers the potential to make state-of-the art inertial and gravitational sensors that will have a wide range of potential applications.

The effects of various additives (Y2O3, Ga2O3, and WO3) on photocatalytic degradation efficiency under UV light-emitting diodes (LEDs) and the optical properties of TiO2 Degussa P25 were investigated using ketoprofen and diclofenac, two non-steroidal anti-inflammatory drugs commonly detected in German rivers. Experimental results demonstrated that thin films containing these additives exhibited similar photocatalytic degradation efficiencies as pure TiO2, achieving a 30% degradation of ketoprofen over 150 min. In contrast, the Y2O3/TiO2 thin film showed significantly improved performance, achieving a 46% degradation of ketoprofen in 180 min. Notably, the Y2O3/TiO2 system was three times more effective in degrading diclofenac compared to pure TiO2. Additionally, the Y2O3/TiO2 photocatalyst retained its activity over three successive cycles with only a slight decrease in efficiency. The photocatalytic degradation of both organic pollutants followed first-order kinetics with all photocatalysts. The investigation included SEM imaging to assess the surface homogeneity of the thin films and UV-vis solid-state spectroscopy to evaluate the impact of the additives on the energy band gap of TiO2.

With a growing number of PCMs and new, suitable PCM candidates, an overview is not only important, but also increasingly complex. Classification of PCM was thus changed significantly in the past decades. A review of classification of PCMs from recent years shows that not only different classification criteria are used, but more important that they are often mixed, used inconsistently, even without a clear goal. Focusing on the main goal of current classification schemes, to give an overview of the material options for the search for new, suitable PCM candidates, including already established PCMs, a consistent classification is developed in a desktop study. For this, first, the general options for classification criteria are reviewed, and then the appropriate ones selected. Then, based on them a new, revised PCM classification is suggested. It is specifically detailed with regard to mixtures; for binary mixtures it is based on a literature review performed within the study. The result also stresses the importance of specific R&D: for pure substances the sources and the chemical modification, and for mixtures their optimization by new compositions, additives, etc.

Prior studies have described positive behavioral, emotional, and social responses to dolls in persons with dementia (PWD), but most have examined formal doll therapy in institutional settings and primarily included women. This study describes two cases of spontaneous doll interactions in male veterans who were participating in a research study of a gentle group movement program at an adult day center. A doll was present at the study site, and two participants chose to interact with it. Researchers analyzed class videos and thematically coded behavioral, emotional, and social responses to the doll. Mr. B was a 90-year-old World War II-era veteran with moderate Alzheimers disease. Behavioral responses (n = 83) toward the doll included gazing, holding, and caressing. Emotional responses (n = 46) included chuckles, smiles, and laughter. Social responses (n = 59) involved conversations about the doll in which his ability to communicate verbally was markedly improved. Mr. C was a 68-year-old Vietnam veteran with mild Lewy body dementia. He also exhibited frequent behavioral (n = 10), social (n = 11) and emotional (n = 8) responses toward the doll. In addition, he reported having an intense, cathartic dream about the doll, crying it brings me back to holding my son or my daughter. These case studies add to the literature supporting the benefits of doll use by PWD by describing the effects of spontaneous doll use in two male veterans. Results suggest that having dolls available and providing a nonjudgmental environment where doll use is encouraged and supported may have profound beneficial effects to diverse populations. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Abstract All climate models project a weakening of the Atlantic Meridional Overturning Circulation (AMOC) strength in response to greenhouse gas forcing. However, the climate impacts of the AMOC decline alone cannot be isolated from other drivers of climate change using existing Coupled Model Intercomparison Project simulations. To address this issue, we conduct idealized experiments using the EC‐Earth3 climate model. We compare an abrupt 4×CO2 simulation with the same experiment, except we artificially fix the AMOC strength at preindustrial levels. With this design, we can formally attribute differences in climate change impacts between these two experiments to the AMOC decline. In addition, we quantify the state‐dependence of AMOC impacts by comparing the aforementioned experiments with a preindustrial simulation in which we artificially reduce the AMOC strength. Our findings demonstrate that AMOC decline impacts are state‐dependent, thus understanding AMOC impacts on future climate change requires targeted model experiments.

Abstract INTRODUCTION There are few widely‐available, evidence‐based options to support quality of life (QOL) for people living with Alzheimer's disease and related dementias. METHODS We performed a randomized, controlled trial with a Waitlist control group to determine whether an online, livestream, mind‐body, group movement program (Moving Together, 1 hour, 2 days/week, 12 weeks) improves QOL in people with cognitive impairment (PWCI) or care partners (CPs) and explore mechanisms of action. The primary outcome for both participants was self‐reported QOL. Secondary outcomes and potential mediators included mobility, isolation, well‐being, cognitive function, and sleep in PWCI and burden, positive emotions, caregiver self‐efficacy, stress management, and sleep in CPs. Blinded assessors collected outcome data at baseline, 12, and 24 weeks. We assessed adverse events including falls through monthly check‐in surveys and collected qualitative data through evaluation surveys. Intention‐to‐treat analyses used linear mixed models to compare mean change over time between groups and calculated standardized effect sizes (ESs). RESULTS Ninety‐seven dyads enrolled (PWCI: age 76 ± 11 years, 43% female, 80% non‐Hispanic White; CPs: age 66 ± 12 years, 78% female, 71% non‐Hispanic White); 15% withdrew before 12 weeks and 22% before 24 weeks. PWCI self‐reported significantly better QOL from baseline to 12 weeks in the Moving Together group compared to the Waitlist group (ES = 0.474, p = 0.048) and CPs self‐reported improved ability to manage stress (ES = 0.484, p = 0.021). Improvements in participant self‐reported QOL were mediated by improvements in their self‐reported well‐being and CP‐reported ability to manage stress. Results were similar when the Waitlist group participated in the program (QOL ES = 0.663, p = 0.006; stress management ES = 0.742, p = 0.002) and were supported by qualitative data. Exploratory analyses suggested possible fall reduction in PWCI. There were no study‐related serious adverse events. DISCUSSION Online programs such as Moving Together offer a scalable strategy for supporting high QOL for PWCI and helping CPs manage stress. TRIAL REGISTRATION ClinicalTrials.gov NCT04621448 Highlights The approval of new medications that slow cognitive decline in people living with Alzheimer's disease and related disorders (ADRD) has raised hope and excitement. However, these medications do not appear to impact quality of life, which is often considered by patients and care partners to be the most important outcome. In this randomized clinical trial, we found that an evidence‐based, online, livestream, mind‐body, group movement program significantly and meaningfully improves self‐rated quality of life in people with ADRD and helps care partners manage stress. Mediation analyses revealed that the key drivers of improvements in participants’ quality of life were improvements in their feelings of well‐being and care partners’ ability to manage stress. Exploratory analyses also suggested a 30% reduction in falls. These results are important because they suggest that an online program, which is available now and can be performed by people from the comfort of home or other location of choice, could be recommended as a complement or alternative to new therapies to help maximize quality of life for people living with ADRD and their care partners.

Loss of elastin due to aging, disease, or injury can lead to impaired tissue function. In this study, de novo tropoelastin (TE) synthesis is investigated in vitro and in vivo using different TE-encoding synthetic mRNA variants after codon optimization and nucleotide modification. Codon optimization shows a strong effect on protein synthesis without affecting cell viability in vitro, whereas nucleotide modifications strongly modulate translation and reduce cell toxicity. Selected TE mRNA variants (3, 10, and 30 μg) are then analyzed in vivo in porcine skin after intradermal application. Administration of 30 μg of native TE mRNA with a me1 Ψ modification or 10 and 30 μg of unmodified codon-optimized TE mRNA is required to increase TE protein expression in vivo. In contrast, just 3 μg of a codon-optimized TE mRNA variant with the me1 Ψ modification is able to increase protein expression. Furthermore, skin toxicity is investigated in vitro by injecting 30 μg of mRNA of selected TE mRNA variants into a human full-thickness skin model, and no toxic effects are observed. Thereby, for the first time, an increased dermal TE synthesis by exogenous administration of synthetic mRNA is demonstrated in vivo. Codon optimization of a synthetic mRNA can significantly increase protein expression and therapeutic outcome.

Theories of embodied cognition hypothesize interdependencies between psychological well-being and physical posture. The purpose of this study was to assess the feasibility of objectively measuring posture, and to explore the relationship between posture and affect and other patient centered outcomes in breast cancer survivors (BCS) with persistent postsurgical pain (PPSP) over a 12-week course of therapeutic Qigong mind-body training. Twenty-one BCS with PPSP attended group Qigong training. Clinical outcomes were pain, fatigue, self-esteem, anxiety, depression, stress and exercise self-efficacy. Posture outcomes were vertical spine and vertical head angles in the sagittal plane, measured with a 3D motion capture system in three conditions: eyes open (EO), eyes open relaxed (EOR) and eyes closed (EC). Assessments were made before and after the Qigong training. The association between categorical variables (angle and mood) was measured by Cramers V. In the EO condition, most participants who improved in fatigue and anxiety scales also had better vertical head values. For the EOR condition, a moderate correlation was observed between changes in vertical head angle and changes in fatigue scale. In the EC condition, most of the participants who improved in measures of fatigue also improved vertical head angle. Additionally, pain severity decreased while vertical spine angle improved. These preliminary findings support that emotion and other patient centered outcomes should be considered within an embodied framework, and that Qigong may be a promising intervention for addressing biopsychosocially complex interventions such as PPSP in BCSs.

BACKGROUND: The Multidimensional Assessment of Interoceptive Awareness (MAIA) is a self-report questionnaire developed by Dr. Mehling that has been widely used to assess multiple dimensions of interoceptive awareness. To further improve the MAIA, Mehling developed the Multidimensional Assessment of Interoceptive Awareness, Version 2 (MAIA-2). The goal of this study is to systematically translate the MAIA-2 into Chinese and to investigate the psychometric properties of the Chinese version (MAIA-2C). MATERIALS AND METHODS: The translation and adaptation of the questionnaire was conducted according to Beatons method. A total number of 627 participants were enrolled and completed the survey. The entire sample was randomly divided into a training sample (n = 300, 47.8%) and a validation sample (n = 327, 52.2%) for a cross-validation. Exploratory factor analysis (EFA) was used to identify the factor structure of the MAIA-2C in the training sample while confirmatory factor analysis (CFA) was used to test the factor structure obtained by EFA. The reliability of the MAIA-2C was indicated by Cronbachs alpha. The convergent and discriminant validity were assessed by Pearson intercorrelations between the MAIA-2C and the Five-Facet Mindfulness Questionnaire (FFMQ) and State-Trait Anxiety Inventory-Trait anxiety (STAI-T). RESULTS: The EFA results showed an initial 10-factor model, but some items (1, 2, 3, 4, 15, and 16) were deleted because they did not yield the original subscale construct, eventually resulting in a 7-factor model. The CFA results represented a good model fit (χ2/df = 2.170, RMSEA = 0.060, SRMR = 0.0810, CFI = 0.890). The Cronbachs alpha was 0.822 for the total scale and ranged from 0.656 to 0.838 for the subscales. The results of convergent and discriminant validity showed that most MAIA-2C subscales were correlated with the average score and subscales of FFMQ (r = -0.342∼0.535, p < 0.05), and all of the subscales of the MAIA-2C showed negative correlations with the STAI-T total score (r = -0.352∼-0.080, p < 0.05). CONCLUSION: The MAIA-2C is a valid and reliable instrument for evaluating multiple dimensions of interoceptive awareness in a Chinese population.

Despite advances in understanding the metabolism of Pseudomonas putida KT2440, a promising bacterial host for producing valuable chemicals from plant-derived feedstocks, a strain capable of producing free fatty acid-derived chemicals has not been developed. Guided by functional genomics, we engineered P. putida to produce medium- and long-chain free fatty acids (FFAs) to titers of up to 670 mg/L. Additionally, by taking advantage of the varying substrate preferences of paralogous native fatty acyl-CoA ligases, we employed a strategy to control FFA chain length that resulted in a P. putida strain specialized in producing medium-chain FFAs. Finally, we demonstrate the production of oleochemicals in these strains by synthesizing medium-chain fatty acid methyl esters, compounds useful as biodiesel blending agents, in various media including sorghum hydrolysate at titers greater than 300 mg/L. This work paves the road to produce high-value oleochemicals and biofuels from cheap feedstocks, such as plant biomass, using this host.

BACKGROUND: High normal resting pCO2 is a risk factor for salt sensitivity of blood pressure (BP) in normotensive humans and has been associated with higher resting systolic BP in postmenopausal women. To date, however, no known studies have investigated the effects of regular practice of voluntary mild hypocapnic breathing on BP in hypertensive patients. The objective of the present research was to test the hypothesis that capnometric feedback training can decrease both resting pCO2 and 24-h BP in a series of mildly hypertensive postmenopausal women. METHODS: A small portable end tidal CO2 (etCO2) monitor was constructed and equipped with software that determined the difference between the momentary etCO2 and a pre-programmed criterion range. The monitor enabled auditory feedback for variations in CO2 outside the criterion range. 16 mildly hypertensive postmenopausal women were individually trained to sustain small decreases in etCO2 during six weekly sessions in the clinic and daily sessions at home. 24-h BP monitoring was conducted before and after the intervention, and in 16 prehypertensive postmenopausal women in a control group who did not engage in the capnometric training. RESULTS: Following the intervention, all 16 capnometric training participants showed decreases in resting etCO2 (- 4.3 ± 0.4 mmHg; p

Abstract Immune checkpoint blockade therapy is beneficial and even curative for some cancer patients. However, the majority don’t respond to immune therapy. Across different tumor types, pre-existing T cell infiltrates predict response to checkpoint-based immunotherapy. Based on in vitro pharmacological studies, mouse models and analyses of human melanoma patients, we show that the cytokine GDF-15 impairs LFA-1/β2-integrin-mediated adhesion of T cells to activated endothelial cells, which is a pre-requisite of T cell extravasation. In melanoma patients, GDF-15 serum levels strongly correlate with failure of PD-1-based immune checkpoint blockade therapy. Neutralization of GDF-15 improves both T cell trafficking and therapy efficiency in murine tumor models. Thus GDF-15, beside its known role in cancer-related anorexia and cachexia, emerges as a regulator of T cell extravasation into the tumor microenvironment, which provides an even stronger rationale for therapeutic anti-GDF-15 antibody development.