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COPD is characterized by irreversible lung tissue damage. We hypothesized that lung-derived mesenchymal stromal cells (LMSCs) reduce alveolar epithelial damage via paracrine processes, and may thus be suitable for cell-based strategies in COPD. We aimed to assess whether COPD-derived LMSCs display abnormalities. LMSCs were isolated from lung tissue of severe COPD patients and non-COPD controls. Effects of LMSC conditioned-medium (CM) on H2O2-induced, electric field- and scratch-injury were studied in A549 and NCI-H441 epithelial cells. In organoid models, LMSCs were co-cultured with NCI-H441 or primary lung cells. Organoid number, size and expression of alveolar type II markers were assessed. Pre-treatment with LMSC-CM significantly attenuated oxidative stress-induced necrosis and accelerated wound repair in A549. Co-culture with LMSCs supported organoid formation in NCI-H441 and primary epithelial cells, resulting in significantly larger organoids with lower type II-marker positivity in the presence of COPD-derived versus control LMSCs. Similar abnormalities developed in organoids from COPD compared to control-derived lung cells, with significantly larger organoids. Collectively, this indicates that LMSCs’ secretome attenuates alveolar epithelial injury and supports epithelial repair. Additionally, LMSCs promote generation of alveolar organoids, with abnormalities in the supportive effects of COPD-derived LMCS, reflective of impaired regenerative responses of COPD distal lung cells.

Abstract Background Nasal gene expression profiling is a promising method to characterize COPD non-invasively. We aimed to identify a nasal gene expression profile to distinguish COPD patients from healthy controls. We investigated whether this COPD-associated gene expression profile in nasal epithelium is comparable with the profile observed in bronchial epithelium. Methods Genome wide gene expression analysis was performed on nasal epithelial brushes of 31 severe COPD patients and 22 controls, all current smokers, using Affymetrix Human Gene 1.0 ST Arrays. We repeated the gene expression analysis on bronchial epithelial brushes in 2 independent cohorts of mild-to-moderate COPD patients and controls. Results In nasal epithelium, 135 genes were significantly differentially expressed between severe COPD patients and controls, 21 being up- and 114 downregulated in COPD (false discovery rate

Abstract Background A screening spiritual history (SSH) is how health professionals (HP) identify patients’ spiritual values, beliefs and preferences (VBPs) in the outpatient setting. We report on attitudes and practices of HPs in the largest Protestant health system in the U.S., the Adventist Health System (AHS). Method Physicians or mid-level practitioners (N = 1082) in AHS-affiliated practices were approached and 513 (47%) agreed to participate. Participants were asked to identify a “spiritual care coordinator” (nurse/staff) and complete a questionnaire that assessed demographics, practice characteristics, religious involvement, and attitudes/practices concerning the SSH. Prevalence and predictors of attitudes/practices were identified. Results Questionnaires were completed by 427 physicians, 86 mid-level practitioners, and 224 nurses/staff (i.e., spiritual care coordinators). Among physicians, 45% agreed that HPs should take a SSH; of mid-level practitioners, 56% agreed; and of nurses/staff, 54% agreed. A significant proportion (range 31–54%) agreed that physicians should take the SSH. Participants indicated a SSH is appropriate for all outpatients (46–57%), well-visit exams (50–60%), the chronically ill (71–75%) and terminally ill (79–82%). A majority agreed the SSH should be documented in the medical record (67–80%). Few (11–17%) currently took a SSH, although most were at least sometimes willing to take a SSH (87–94%) or review the results thereof (86–98%). Self-rated importance of religion was the strongest predictor of SSH attitudes/practices. Conclusions Many in the AHS say a SSH should be done, are willing to do it, and are willing to review the results, although few currently do so. Education, training, and support may help HPs identify and address patients' spiritual VBPs.

Microglia and astrocytes can quench metal toxicity to maintain tissue homeostasis, but with age, increasing glial dystrophy alongside metal dyshomeostasis may predispose the aged brain to acquire neurodegenerative diseases. The aim of the present study was to investigate age-related changes in brain metal deposition along with glial distribution in normal C57Bl/6J mice aged 2-, 6-, 19- and 27-months (n = 4/age). Using synchrotron-based X-ray fluorescence elemental mapping, we demonstrated age-related increases in iron, copper, and zinc in the basal ganglia (p < 0.05). Qualitative assessments revealed age-associated increases in iron, particularly in the basal ganglia and zinc in the white matter tracts, while copper showed overt enrichment in the choroid plexus/ventricles. Immunohistochemical staining showed augmented numbers of microglia and astrocytes, as a function of aging, in the basal ganglia (p < 0.05). Moreover, qualitative analysis of the glial immunostaining at the level of the fimbria and ventral commissure, revealed increments in the number of microglia but decrements in astroglia, in older aged mice. Upon morphological evaluation, aged microglia and astroglia displayed enlarged soma and thickened processes, reminiscent of dystrophy. Since glial cells have major roles in metal metabolism, we performed linear regression analysis and found a positive association between iron (R2 = 0.57, p = 0.0008), copper (R2 = 0.43, p = 0.0057), and zinc (R2 = 0.37, p = 0.0132) with microglia in the basal ganglia. Also, higher levels of iron (R2 = 0.49, p = 0.0025) and zinc (R2 = 0.27, p = 0.040) were correlated to higher astroglia numbers. Aging was accompanied by a dissociation between metal and glial levels, as we found through the formulation of metal to glia ratios, with regions of basal ganglia being differentially affected. For example, iron to astroglia ratio showed age-related increases in the substantia nigra and globus pallidus, while the ratio was decreased in the striatum. Meanwhile, copper and zinc to astroglia ratios showed a similar regional decline. Our findings suggest that inflammation at the choroid plexus, part of the blood-cerebrospinal-fluid barrier, prompts accumulation of, particularly, copper and iron in the ventricles, implying a compromised barrier system. Moreover, age-related glial dystrophy/senescence appears to disrupt metal homeostasis, likely due to induced oxidative stress, and hence increase the risk of neurodegenerative diseases.

Background: Moral injury (MI) involves distress over having transgressed or violated core moral boundaries, accompanied by feelings of guilt, shame, self-condemnation, loss of trust, loss of meaning, and spiritual struggles. MI is often found in Veterans and Active Duty Military personnel with posttraumatic stress disorder (PTSD). MI is widespread among those with PTSD symptoms, adversely affects mental health, and may increase risk of suicide; however, MI is often ignored and neglected by mental health professionals who focus their attention on PTSD only.Methods: A review of the literature between 1980 and 2018 conducted in 2018 is presented here to identify scales used to assess MI. Databases used in this review were PsychInfo, PubMed (Medline), and Google Scholar. Search terms were “moral injury,” “measuring,” “screening,” “Veterans,” and “Active Duty Military.” Inclusion criteria were quantitative measurement of MI and health outcomes, Veteran or Active Duty Military status, and peer-review publication. Excluded were literature reviews, dissertations, book chapters, case reports, and qualitative studies.Results: Of the 730 studies identified, most did not meet eligibility criteria, leaving 118 full text articles that were reviewed, of which 42 did not meet eligibility criteria. Of the remaining 76 studies, 34 were duplicates leaving 42 studies, most published in 2013 or later. Of 22 studies that assessed MI, five used scales assessing multiple dimensions, and 17 assessed only one or two aspects (e.g., guilt, shame, or forgiveness). The remaining 20 studies used one of the scales reported in the first 22. Of the five scales assessing multiple dimensions of MI, two assess both morally injurious events and symptoms and the remaining three assess symptoms only. All studies were cross-sectional, except three that tested interventions.Conclusions: MI in the military setting is widespread and associated with PTSD symptom severity, anxiety, depression, and risk of suicide in current or former military personnel. Numerous measures exist to assess various dimensions of MI, including five multidimensional scales, although future research is needed to identify cutoff scores and clinically significant change scores. Three multidimensional measures assess MI symptoms alone (not events) and may be useful for determining if treatments directed at MI may both reduce symptoms and impact other mental health outcomes including PTSD.

Studies have shown that traumatic experiences are positively associated with risk of suicidal behaviors, whereas religiosity has been found to be negatively associated with that risk. How exactly religiosity interacts with traumatic experiences in its relationship to suicidal behaviors remains unclear. The current study examined the moderating effects of religiosity on the relationship between traumatic experiences and suicidal behaviors in 5,301 college students in northwestern China. Results indicated a strong positive association between traumatic experiences and suicidal behaviors (β = .46, p < .01), and a weak inverse association between religiosity and suicidal behaviors (β = –.06, p < .01). However, a significant interaction emerged between religiosity and traumatic experiences in their effect on suicidal behaviors (β = –.23, p < .01). These findings suggest that religiosity may play a role in reducing the risk of traumatic experiences-induced suicidal behaviors among college students in a largely secular society.

This review identified associations between illness perception and health outcomes of patients with a medical diagnosis included in the Hospital Readmissions Reduction Program. Inclusion criteria were English language, use of quantitative methodology, health outcomes specified, and identifiable effect size and statistical significance of the relationship. Most of the 31 studies in this review showed that favorable illness perception has been associated with better health outcomes, while unfavorable illness perception has been associated with worse outcomes. A multifaceted approach might include behavioral, clinical, educational, and psychosocial components to improve one’s illness perception through educative, cognitive-behavioral, or psychodynamic counseling.

Background: Salivary metabolomics is rapidly advancing. Aim and methods: To determine the extent to which salivary metabolites reflects host or microbial metabolic activity whole-mouth saliva (WMS), parotid saliva (PS) and plasma collected contemporaneously from healthy volunteers were analysed by 1H-NMR spectroscopy. Spectra underwent principal component analysis and k-means cluster analysis and metabolite quantification. WMS samples were cultured on both sucrose and peptide-enriched media. Correlation between metabolite concentration and bacterial load was assessed. Results: WMS contained abundant short-chain fatty acids (SCFAs), which were minimal in PS and plasma. WMS spectral exhibited greater inter-individual variation than those of PS or plasma (6.7 and 3.6 fold, respectively), likely reflecting diversity of microbial metabolomes. WMS bacterial load correlated strongly with SCFA levels. Additional WMS metabolites including amines, amino acids and organic acids were positively correlated with bacterial load. Lactate, urea and citrate appeared to enter WMS via PS and the circulation. Urea correlated inversely with WMS bacterial load. Conclusions: Oral microbiota contribute significantly to the WMS metabolome. Several WMS metabolites (lactate, urea and citrate) are derived from the host circulation. WMS may be particularly useful to aid diagnosis of conditions reflective of dysbiosis. WMS could also complement other gastrointestinal fluids in future metabolomic studies.

This paper describes the development and initial psychometric testing of the baseline Spirituality Survey (SS-1) from the Study on Stress, Spirituality, and Health (SSSH). The SS-1 contains a mixture of items selected from validated existing scales and new items generated to measure important constructs not captured by existing instruments, and our purpose here was to establish the validity of new and existing measures in a racially/ethnically diverse sample. Psychometric properties of the SS-1 were evaluated using standard psychometric analyses in 4563 SSSH participants. Predictive validity of SS-1 scales was assessed in relation to the physical and mental health component scores from the Short-Form 12 Health Survey (SF-12). Scales exhibited adequate to strong psychometric properties and demonstrated construct and predictive validity. Overall, the correlational findings provided solid evidence that the SS-1 scales are associated with a wide range of relevant R/S attitudes, mental health, and to a lesser degree physical health.

Background: Trust represents a complex emotion and interpersonal concept which assumes abandoning control over a given situation or set of circumstances, in turn yielding such control to another party. Advances in our knowledge of post-traumatic stress disorder and moral injury have underscored the need to more closely examine how trust stands to impact health outcomes in these disorders. The aim of the present study is to examine and identify relationships linking general trust with select health outcomes in a mixed sample of Veterans and Service members with a self-reported history of deployment to a combat theater and PTSD symptomatology.Methods: This study applied a cross-sectional methodology, surveying n = 427 participants recruited across six sites. This included 373 Veterans and 54 active duty Service members in the United States. Measures included demographic characteristics, combat exposure, general trust, post-traumatic stress disorder symptomatology, depressive/anxiety symptomatology, alcohol use, social involvement, religiosity, and physical health. Data were analyzed descriptively as well as using Pearson correlations, Student's t-test, and multivariate regression.Results: Several significant relationships were identified, indicating an inverse relationship between trust and PTSD, depressive, and anxiety symptomatology. Greater levels of trust were also significantly associated with increased social interaction and religiosity. Lastly, no significant associations were identified with either physical functioning or pain level.Conclusion: The findings suggest that trust is correlated with a variety of health outcomes in Veterans and Service members affected by combat-related PTSD. Additional, hypothesis-driven research, informed by longitudinal data, is needed to better understand how trust stands to impact health outcomes, including the development of strategies and intervention options for repairing trust.

Objective: Few quantitative studies have examined the effect of religious involvement on the course of bipolar disorder (BD). We investigated the effects of religious activity and coping behaviors on the course of depression, mania, and quality of life (QoL) in patients with BD. Methods: Two-year longitudinal study of 168 outpatients with BD. Linear regression was used to examine associations between religious predictors and outcome variables (manic symptoms, depression, QoL), controlling for sociodemographic variables. Results: Among the 158 patients reassessed after 2 years, positive religious coping at T1 predicted better QoL across all four domains: physical (β = 10.2, 95%CI 4.2 to 16.1), mental (β = 13.4, 95%CI 7.1 to 19.7), social (β = 10.5, 95%CI 3.6 to 17.33), and environmental (β = 11.1, 95%CI 6.2 to 16.1) at T2. Negative religious coping at T1 predicted worse mental (β = -28.1, 95%CI -52.06 to -4.2) and environmental (β = -20.4, 95%CI -39.3 to -1.6) QoL. Intrinsic religiosity at T1 predicted better environmental QoL (β = 9.56, 95%CI 2.76 to 16.36) at T2. Negative religious coping at T1 predicted manic symptoms (β = 4.1) at T2. Conclusion: Religiosity/spirituality (R/S) may influence the QoL of patients with BD over time, even among euthymic patients. Targeting R/S (especially positive and negative religious coping) in psychosocial interventions may enhance the quality of recovery in patients with BD.

Background Post-traumatic stress disorder (PTSD) is a debilitating disorder, and current treatments leave the majority of patients with unresolved symptoms. Moral injury (MI) may be one of the barriers that interfere with recovery from PTSD, particularly among current or former military service members. Objective Given the psychological and spiritual aspects of MI, an intervention that addresses MI using spiritual resources in addition to psychological resources may be particularly effective in treating PTSD. To date, there are no existing empirically based individual treatments for PTSD and MI that make explicit use of a patient’s spiritual resources, despite the evidence that spiritual beliefs/activities predict faster recovery from PTSD. Method To address this gap, we adapted Cognitive Processing Therapy (CPT), an empirically validated treatment for PTSD, to integrate clients’ spiritual beliefs, practices, values, and motivations. We call this treatment Spiritually Integrated CPT (SICPT). Results This article describes this novel manualized therapeutic approach for treating MI in the setting of PTSD for spiritual/religious clients. We provide a description of SICPT and a brief summary of the 12 sessions. Then, we describe a case study in which the therapist helps a client use his spiritual resources to resolve MI and assist in the recovery from PTSD. Conclusion SICPT may be a helpful way to reduce PTSD by targeting MI, addressing spiritual distress, and using a client’s spiritual resources. In addition to the spiritual version (applicable for those of any religion and those who do not identify as religious), we have also developed 5 religion-specific manuals (Christianity, Judaism, Islam, Buddhism, and Hinduism) for clients who desire a more religion-specific approach.

Single cell whole genome amplification is susceptible to amplification biases that impact the accuracy of single cell sequencing data. To address this, we have developed a microfluidic device for the isolation and purification of genomic DNA from individual cells. The device uses a micropillar array to physically capture single cells and its chromosomal DNA upon extraction. The extracted DNA is immobilized within the micropillar array in a way that allows isothermal amplification. In this system, whole genome amplification of the single cell is carried out under a continual fluid flow within the microfluidic channel. We have demonstrated the process for amplification of individual human cancer cell genomes from the HeLa cell line. By sampling select gene loci along the human genome and performing whole exome sequencing, we demonstrate improved genome coverage and reduced amplification bias compared to amplification of single cells deposited in wells by fluorescence activated cell sorting.