Experiences of using digital mindfulness-based interventions: Rapid scoping review and thematic synthesis

Background: Digital mindfulness-based interventions (MBIs) are a promising approach to deliver accessible and scalable mindfulness training and have been shown to improve a range of health outcomes. However, the success of digital MBIs is reliant on adequate engagement, which remains a crucial challenge. Understanding people’s experiences of using digital MBIs and identifying the core factors that facilitate or act as barriers to engagement is essential to inform intervention development and maximize engagement and outcomes. Objective: This study aims to systematically map the literature on people’s experiences of using digital MBIs that target psychosocial variables (eg, anxiety, depression, distress, and well-being) and identify key barriers to and facilitators of engagement. Methods: We conducted a scoping review to synthesize empirical qualitative research on people’s experiences of using digital MBIs. We adopted a streamlined approach to ensure that the evidence could be incorporated into the early stages of intervention development. The search strategy identified articles with at least one keyword related to mindfulness, digital, user experience, and psychosocial variables in their title or abstract. Inclusion criteria specified that articles must have a qualitative component, report on participants’ experiences of using a digital MBI designed to improve psychosocial variables, and have a sample age range that at least partially overlapped with 16 to 35 years. Qualitative data on user experience were charted and analyzed using inductive thematic synthesis to generate understandings that go beyond the content of the original studies. We used the Quality of Reporting Tool to critically appraise the included sources of evidence. Results: The search identified 510 studies, 22 (4.3%) of which met the inclusion criteria. Overall, the samples were approximately 78% female and 79% White; participants were aged between 16 and 69 years; and the most used measures in intervention studies were mindfulness, psychological flexibility, and variables related to mental health (including depression, anxiety, stress, and well-being). All studies were judged to be adequately reported. We identified 3 themes characterizing barriers to and facilitators of engagement: responses to own practice (ie, negative reactions to one’s own practice are common and can deplete motivation), making mindfulness a habit (ie, creating a consistent training routine is essential yet challenging), and leaning on others (ie, those engaging depend on someone else for support). Conclusions: The themes identified in this review provide crucial insights as to why people frequently stop engaging with digital MBIs. Researchers and developers should consider using person-based coparticipatory methods to improve acceptability of and engagement with digital MBIs, increase their effectiveness, and support their translation to real-world use. Such strategies must be grounded in relevant literature and meet the priorities and needs of the individuals who will use the interventions

Political Influence Associates With Cortisol and Health Among Egalitarian Forager-Farmers

Background and objectives: Low social status increases risk of disease due, in part, to the psychosocial stress that accompanies feeling subordinate or poor. Previous studies report that chronic stress and chronically elevated cortisol can impair cardiovascular and immune function. We test whether lower status is more benign in small-scale, relatively egalitarian societies, where leaders lack coercive authority and there is minimal material wealth to contest. Methodology: Among Tsimane’ forager-horticulturalists of lowland Bolivia, we compare informal political influence among men with urinary cortisol, immune activation (innate and acquired), and morbidity as assessed during routine medical exams. Results: After controlling for potential confounds, we find that politically influential men have lower cortisol, and that this association is partly attributable to access to social support. Cortisol is positively associated with men’s income, which may reflect chronic psychosocial stress from market involvement. Greater influence is also associated with lower probability of respiratory infection, which is a frequent source of morbidity among Tsimane’. Among men who lost influence over a 4-year period, cortisol and probability of respiratory infection were higher the greater the decline in influence. Conclusions and implications: Deleterious effects of low status on health are not merely ‘diseases of civilization’ but may result from how (even subtle) status differences structure human behavior

Nachweis und Quantifizierung von Drogen und anderen Fremdstoffen in Blutspuren auf verschiedenen Trägermaterialien

Es wurde ein gaschromatographisch-massenspektrometrisches (GC/MS)-Verfahren zum Screening und Nachweis von Morphin (4,5alpha-Epoxy-17-methyl-7-morphinen-3,6alpha-diol), Codein (4,5alpha-Epoxy-3-methoxy-17-methyl-7-morphinen-6alpha-ol), Heroin (4,5alpha-Epoxy-17-methyl-7-morphinen-3,6alpha-diyldiacetat), Kokain ((-)-Methyl-[3beta-benzoyloxy-2beta(1alphaH,5alphaH)-tropancarboxylat]), Benzoylecgonin (Tropin-2-carbonsäure-benzoylester, Methylecgonin (Tropin-3-carbonsäure-methylester), Cocethylen ((-)-Ethyl-[3beta-benzoyloxy-2beta(1alphaH,5alphaH)-tropancarboxylat]), THC (Delta-9-tetrahydrocannabinol), THC-Carbonsäure (11-Nor-9-carboxy-delta-9-tetrahydrocannabinol),, 11-OH-THC (11-hydroxy-delta-9-tetrahydrocannabinol), Amphetamin ((±)-alpha-Methylphenethylamin), Methamphetamin (N,alpha-Dimethylphenethylamin), MDA (Methylendioxyamphetamin; Tenamfetamin, alpha-Methyl-3,4-methylendioxy-phenethylamin), MDMA (Methylendioxymethamphetamin; N,alpha-Dimethyl-3,4-methylendioxy-phenethylamin) und MBDB (N-Methylbenzodioxazolylbutanamin) in kleinen Blutproben und Blutspuren unter Verwendung von Festphasen-SPE-Säulen und einem Pipettierroboter (Gilson Aspec XL) beschrieben. Die Nachweisgrenzen liegen zwischen 1,62 und 4,10 ng / 50 µl Spot (Amphetaminderivate), 0,15 und 0,82 ng / 50 µl Spot (Cannabinoide), 1,67 – 4,70 ng / 50 µl Spot (Kokain und dessen Derivate) sowie 4,53 und 4,91 ng / 50 µl Spot (Opiate) und die Korrelationsfaktoren zwischen 0,9957 und 0,9999. Weiterhin wurde die Nachweisbarkeit auf verschiedenen Spurenträgern (Holz, Stoff (Textil), Metall, Fliesen und Glas) untersucht. Dabei ergab sich, dass ein qualitativer Nachweis noch nach mindestens 64 Tagen möglich war, die quantitative Bestimmung jedoch auf Schwierigkeiten stieß. Ursachen hierfür sind beispielsweise Chargenunterschiede der Säulenmaterialien und andere Effekte, die beim Arbeiten im spurenanalytischen Bereich in der Nähe der Nachweis- und unteren Bestimmungsgrenze von großem Einfluss sind. Mit Hilfe der im Rahmen dieser Arbeit entwickelten Methode konnten 2 spektakuläre Kriminalfälle aufgeklärt werden.A GC/MS-method is developed for the screening and detection of morphine (4,5a-epoxy-17-methyl-7-morphinen-3,6a-diol), codeine (4,5a-epoxy-3-methoxy-17-methyl-7-morphinen-6a-ol), heroin (4,5a-epoxy-17-methyl-7-morphinen-3,6a-diyldiacetate), cocaine ((-)-methyl-[3beta-benzoyloxy-2ß(1alphaH,5alphaH)-tropancarboxylate]), benzoylecgonine (tropin-2-carboxylic acid-benzoylester, methylecgonin (tropin-3-carboxylic acid-methylester), cocethylene ((-)-ethyl-[3beta-benzoyloxy-2beta(1alphaH,5alphaH)-tropancarboxylate]), THC (delta-9-tetrahydrocannabinol), THC-carbonic acid (11-Nor-9-carboxy-delta-9-tetrahydrocannabinol), 11-OH-THC (11-hydroxy-delta-9-tetrahydrocannabinol), amphetamine ((±)-alpha-methylphenethylamine), methamphetamin (N,alpha-dimethylphenethylamine), MDA (methylendioxyamphetamine; tenamfetamine, alpha-methyl-3,4-methylendioxy-phenethylamine), MDMA (methylenedioxymethamphetamine; N,alpha-dimethyl-3,4-methylendioxy-phenethylamine) und MBDB (N-methylbenzodioxazolylbutanamine) in small blood samples and bloodstains using solid phase SPE columns and a pipetting robot (Gilson Aspec XL). The detection limits are in the order of 1.62 – 4.10 ng / 50 µl spot (amphetamines), 0.15 – 0.82 ng / 50 µl spot (cannabinoids), 1.67 – 4.70 ng / 50 µl spot (cocaine and derivatives) and 4.53 – 4.91 ng / 50 µl spot (opiates) and the correlation factors are between 0.9957 and 0.9999. The method has proven useful in forensic cases with only small sample volumes or bloodstains. Furthermore the detectability was tested using different trace-carriers (wood, textiles, metal, floor-tiles und glass). These investigations resulted in qualitative detectabilities within at least 64 days. The quantitative determination however raised difficulties, mainly caused by different brands of columns and other effects which are of important influence when working in the analytical range near the detection- and lower determination limit, respectively. By means of the methods developed within the scope of this study, two spectacular crime cases could be cleared up

Substantively Lowered Levels of Pantothenic Acid (Vitamin B5) in Several Regions of the Human Brain in Parkinson’s Disease Dementia

From MDPI via Jisc Publications RouterHistory: accepted 2021-08-23, pub-electronic 2021-08-25Publication status: PublishedFunder: Endocore Research Associates, NZ; Grant(s): 60147, 3626585; 3702766, JXU058, UOAX0815Funder: Maurice and Phyllis Paykel Trust; Grant(s): 3627036Funder: Maurice Wilkins Centre for Molecular Biodiscovery; Grant(s): 9341-3622506Funder: Oakley Mental Health Research Foundation; Grant(s): 3456030; 3627092; 3701339; 3703253; 3702870Funder: Neurological Foundation of New Zealand; Grant(s): N/AFunder: Medical Research Council; Grant(s): MR/L010445/1 and MR/L011093/1Funder: Alzheimer’s Research UK; Grant(s): ARUK-PPG2014B-7Pantothenic acid (vitamin B5) is an essential trace nutrient required for the synthesis of coenzyme A (CoA). It has previously been shown that pantothenic acid is significantly decreased in multiple brain regions in both Alzheimer’s disease (ADD) and Huntington’s disease (HD). The current investigation aimed to determine whether similar changes are also present in cases of Parkinson’s disease dementia (PDD), another age-related neurodegenerative condition, and whether such perturbations might occur in similar regions in these apparently different diseases. Brain tissue was obtained from nine confirmed cases of PDD and nine controls with a post-mortem delay of 26 h or less. Tissues were acquired from nine regions that show high, moderate, or low levels of neurodegeneration in PDD: the cerebellum, motor cortex, primary visual cortex, hippocampus, substantia nigra, middle temporal gyrus, medulla oblongata, cingulate gyrus, and pons. A targeted ultra–high performance liquid chromatography—tandem mass spectrometry (UHPLC-MS/MS) approach was used to quantify pantothenic acid in these tissues. Pantothenic acid was significantly decreased in the cerebellum (p = 0.008), substantia nigra (p = 0.02), and medulla (p = 0.008) of PDD cases. These findings mirror the significant decreases in the cerebellum of both ADD and HD cases, as well as the substantia nigra, putamen, middle frontal gyrus, and entorhinal cortex of HD cases, and motor cortex, primary visual cortex, hippocampus, middle temporal gyrus, cingulate gyrus, and entorhinal cortex of ADD cases. Taken together, these observations indicate a common but regionally selective disruption of pantothenic acid levels across PDD, ADD, and HD

Severe and Regionally Widespread Increases in Tissue Urea in the Human Brain Represent a Novel Finding of Pathogenic Potential in Parkinson’s Disease Dementia

From Frontiers via Jisc Publications RouterHistory: collection 2021, received 2021-05-18, accepted 2021-09-30, epub 2021-10-22Publication status: PublishedWidespread elevations in brain urea have, in recent years, been reported in certain types of age-related dementia, notably Alzheimer’s disease (AD) and Huntington’s disease (HD). Urea increases in these diseases are substantive, and approximate in magnitude to levels present in uraemic encephalopathy. In AD and HD, elevated urea levels are widespread, and not only in regions heavily affected by neurodegeneration. However, measurements of brain urea have not hitherto been reported in Parkinson’s disease dementia (PDD), a condition which shares neuropathological and symptomatic overlap with both AD and HD. Here we report measurements of tissue urea from nine neuropathologically confirmed regions of the brain in PDD and post-mortem delay (PMD)-matched controls, in regions including the cerebellum, motor cortex (MCX), sensory cortex, hippocampus (HP), substantia nigra (SN), middle temporal gyrus (MTG), medulla oblongata (MED), cingulate gyrus, and pons, by applying ultra-high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS). Urea concentrations were found to be substantively elevated in all nine regions, with average increases of 3–4-fold. Urea concentrations were remarkably consistent across regions in both cases and controls, with no clear distinction between regions heavily affected or less severely affected by neuronal loss in PDD. These urea elevations mirror those found in uraemic encephalopathy, where equivalent levels are generally considered to be pathogenic, and those previously reported in AD and HD. Increased urea is a widespread metabolic perturbation in brain metabolism common to PDD, AD, and HD, at levels equal to those seen in uremic encephalopathy. This presents a novel pathogenic mechanism in PDD, which is shared with two other neurodegenerative diseases

The SARS-CoV-2 spike protein binds and modulates estrogen receptors

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike (S) protein binds angiotensin-converting enzyme 2 as its primary infection mechanism. Interactions between S and endogenous proteins occur after infection but are not well understood. We profiled binding of S against >9000 human proteins and found an interaction between S and human estrogen receptor alpha (ER alpha). Using bioinformatics, supercomputing, and experimental assays, we identified a highly conserved and functional nuclear receptor coregulator (NRC) LXD-like motif on the S2 sub-unit. In cultured cells, S DNA transfection increased ER alpha cytoplasmic accumulation, and S treatment induced ER-dependent biological effects. Non-invasive imaging in SARS-CoV-2-infected hamsters localized lung pathology with increased ER alpha lung levels. Postmortem lung experiments from infected hamsters and humans confirmed an increase in cytoplasmic ER alpha and its colocalization with S in alveolar macrophages. These findings describe the discovery of a S-ER alpha interaction, imply a role for S as an NRC, and advance knowledge of SARS-CoV-2 biology and coronavirus disease 2019 pathology

Regulatory modules function in a non-autonomous manner to control transcription of the mbp gene

Multiple regulatory modules contribute to the complex expression programs realized by many loci. Although long thought of as isolated components, recent studies demonstrate that such regulatory sequences can physically associate with promoters and with each other and may localize to specific sub-nuclear transcription factories. These associations provide a substrate for putative interactions and have led to the suggested existence of a transcriptional interactome. Here, using a controlled strategy of transgenesis, we analyzed the functional consequences of regulatory sequence interaction within the myelin basic protein (mbp) locus. Interactions were revealed through comparisons of the qualitative and quantitative expression programs conferred by an allelic series of 11 different enhancer/inter-enhancer combinations ligated to a common promoter/reporter gene. In a developmentally contextual manner, the regulatory output of all modules changed markedly in the presence of other sequences. Predicted by transgene expression programs, deletion of one such module from the endogenous locus reduced oligodendrocyte expression levels but unexpectedly, also attenuated expression of the overlapping golli transcriptional unit. These observations support a regulatory architecture that extends beyond a combinatorial model to include frequent interactions capable of significantly modulating the functions conferred through regulatory modules in isolation

Wnt-reporter expression pattern in the mouse intestine during homeostasis

<p>Abstract</p> <p>Background</p> <p>The canonical Wnt signaling pathway is a known regulator of cell proliferation during development and maintenance of the intestinal epithelium. Perturbations in this pathway lead to aberrant epithelial proliferation and intestinal cancer. In the mature intestine, proliferation is confined to the relatively quiescent stem cells and the rapidly cycling transient-amplifying cells in the intestinal crypts. Although the Wnt signal is believed to regulate all proliferating intestinal cells, surprisingly, this has not been thoroughly demonstrated. This important determination has implications on intestinal function, especially during epithelial expansion and regeneration, and warrants an extensive characterization of Wnt-activated cells.</p> <p>Methods</p> <p>To identify intestinal epithelial cells that actively receive a Wnt signal, we analyzed intestinal Wnt-reporter expression patterns in two different mouse lines using immunohistochemistry, enzymatic activity, <it>in situ </it>hybridization and qRT-PCR, then corroborated results with reporter-independent analyses. Wnt-receiving cells were further characterized for co-expression of proliferation markers, putative stem cell markers and cellular differentiation markers using an immunohistochemical approach. Finally, to demonstrate that Wnt-reporter mice have utility in detecting perturbations in intestinal Wnt signaling, the reporter response to gamma-irradiation was examined.</p> <p>Results</p> <p>Wnt-activated cells were primarily restricted to the base of the small intestinal and colonic crypts, and were highest in numbers in the proximal small intestine, decreasing in frequency in a gradient toward the large intestine. Interestingly, the majority of the Wnt-reporter-expressing cells did not overlap with the transient-amplifying cell population. Further, while Wnt-activated cells expressed the putative stem cell marker Musashi-1, they did not co-express DCAMKL-1 or cell differentiation markers. Finally, gamma-irradiation stimulated an increase in Wnt-activated intestinal crypt cells.</p> <p>Conclusion</p> <p>We show, for the first time, detailed characterization of the intestine from Wnt-reporter mice. Further, our data show that the majority of Wnt-receiving cells reside in the stem cell niche of the crypt base and do not extend into the proliferative transient-amplifying cell population. We also show that the Wnt-reporter mice can be used to detect changes in intestinal epithelial Wnt signaling upon physiologic injury. Our findings have an important impact on understanding the regulation of the intestinal stem cell hierarchy during homeostasis and in disease states.</p