Background Nearly two-thirds of elderly patients treated for depression fail to achieve symptomatic remission and functional recovery with first-line pharmacotherapy. In this study, we ask whether a ...mind–body exercise, Tai Chi Chih (TCC), added to escitalopram will augment the treatment of geriatric depression designed to achieve symptomatic remission and improvements in health functioning and cognitive performance. Methods One hundred twelve older adults with major depression age 60 years and older were recruited and treated with escitalopram for approximately 4 weeks. Seventy-three partial responders to escitalopram continued to receive escitalopram daily and were randomly assigned to 10 weeks of adjunct use of either 1) TCC for 2 hours per week or 2) health education (HE) for 2 hours per week. All participants underwent evaluations of depression, anxiety, resilience, health-related quality of life, cognition, and inflammation at baseline and during 14-week follow-up. Results Subjects in the escitalopram and TCC condition were more likely to show greater reduction of depressive symptoms and to achieve a depression remission as compared with those receiving escitalopram and HE. Subjects in the escitalopram and TCC condition also showed significantly greater improvements in 36-Item Short Form Health Survey physical functioning and cognitive tests and a decline in the inflammatory marker, C-reactive protein, compared with the control group. Conclusion Complementary use of a mind–body exercise, such as TCC, may provide additional improvements of clinical outcomes in the pharmacologic treatment of geriatric depression.
Objectives To evaluate the effects of a behavioral intervention, Tai Chi Chih (TCC) on circulating markers of inflammation in older adults. Design A prospective, randomized, controlled trial with ...allocation to two arms, TCC and health education (HE), 16 weeks of intervention administration, and 9 weeks follow-up. Participants A total of 83 healthy older adults, aged 59 to 86 years. Measurements The primary endpoint was circulating levels of interleukin 6 (IL-6). Secondary outcomes were circulating levels of C-reactive protein, soluble IL-1 receptor antagonist, soluble IL-6 receptor, soluble intercellular adhesion molecule, and IL-18. Severity of depressive symptoms, sleep quality, and physical activity was also assessed over the treatment trial. Results Among those older adults with high levels of IL-6 at entry, a trend for a treatment group by time interaction was found (F1,70 = 3.48, p = 0.07), in which TCC produced a drop of IL-6 levels comparable to those found in TCC and HE subgroups who had low levels of IL-6 at entry (t72 's = 0.80, 1.63, p's >0.10), whereas IL-6 in HE remained higher than the TCC and HE subgroups with low entry IL-6 (t72 = 2.47, p = 0.02; t72 = 1.71, p = 0.09). Decreases in depressive symptoms in the two treatment groups correlated with decreases of IL-6 (r = 0.28, p <0.05). None of the other cellular markers of inflammation changed in TCC versus HE. Conclusion TCC can be considered a useful behavioral intervention to reduce circulating levels of IL-6 in older adults who show elevated levels of this inflammatory marker and are at risk for inflammation-related morbidity.
•Computer tomography (CT) is examined as a tool to classify fresh in vivo chestnuts.•Classification accuracy is 86%, 91% and 96% for 5-, 3- and 2-classes respectively.•Information to develop in-line ...chestnut internal quality sorting is offered.•CT technology is able to detect internal decay of chestnuts.
X-ray computed tomography (CT) is an effective noninvasive tool to visualize fresh agricultural commodities’ internal components and quality attributes, including those of chestnuts (Castanea spp). There is no procedure to automatically, effectively and efficiently classify fresh commodities from a continuous inline flow through a CT system. If the information obtained by CT scanning of fresh agricultural commodities is to be used in an industrial application (e.g. inline sorting), automated interpretation of CT images is essential. For this purpose, an image analysis method (algorithm) for the automatic classification of CT images obtained from 2848 fresh chestnuts (cv. ‘Colossal’ and ‘Chinese seedlings’), during the harvesting years from 2009 to 2012, was developed and tested. Classification accuracy was evaluated by comparing the classes obtained from six CT images per chestnut to their internal quality assessment. An experienced human rater performed internal quality assessment by visually and invasively rating fresh chestnut internal decay severity (quality) into 5-, 3- and 2-classes.
After CT image preprocessing, cropping and segmentation, 1194 grayscale intensity and textural features were extracted from six resultant CT images per sample. Relevant features were selected using a sequential forward selection algorithm with the Fisher discriminant objective function. 86, 155 and 126 features were effective in designing a quadratic discriminant classifier with a 4-fold cross-validation with a performance accuracy of 85.9%, 91.2% and 96.1% for 5, 3 and 2 classes, respectively. This method is accurate and objective in determining fresh chestnut internal quality, and the methodology is applicable to automatic noninvasive inline CT sorting system development.
BTLA expression contributes to increased septic morbidity, mortality, and decreased innate cell activity in mice, while BTLA+ blood monocyte levels increase in septic ICU patients.
A proper innate ...inflammatory response is essential for prevention of the systemic inflammation associated with sepsis. BTLA is an immune‐regulatory receptor demonstrated to be expressed not only on adaptive immune populations and have potent inhibitory effects on CD4+ T cells but is also expressed on innate cell populations (CD11c+ and CD11b+ cells) and has been shown to diminish pathogen clearance following bacterial and parasite infection. The role of BTLA in sepsis and the mechanisms by which BTLA alters pathogen clearance, however, have not been addressed clearly. Here, we show that following acute experimental sepsis induction in mice (CLP), the number of infiltrating BTLA‐ and HVEM (the ligand for BTLA)‐expressing macrophages, inflammatory monocytes, mature and immature DCs, and neutrophils increased in the peritoneum compared with sham surgery, suggesting that a high level of HVEM:BTLA interactions occurs between these cells at the site of septic insult. Given this, we evaluated BTLA−/− mice, 24 h post‐CLP, and observed a marked increase in the degree of activation on these cell populations, as well as a reduction in peritoneal bacterial burden and IL‐10 induction, and most importantly, BTLA−/− mice exhibited a higher rate of survival and protection from organ injury when compared with WT mice. Such changes were not restricted to experimental mice, as circulating BTLA+ and HVEM+ monocytes and HVEM+ granulocytes were increased in septic ICU patients, supporting a role for BTLA and/or HVEM as potential, novel diagnostic markers of innate immune response/status and as therapeutic targets of sepsis.
Machine learning is a promising technique to develop models, which extract relevant information from image data. This study applies convolutional neural networks trained end-to-end to predict the ...mechanical properties of apples (var. Granny Smith) from micro-CT image data collected during in vitro gastric digestion. Models were trained to directly output compression curves, allowing for representation of complex curve shapes, which changed throughout the digestion process. Models evaluated using 3-fold cross-validation demonstrated high predictive performance, with RMSE of 4.36 N and R2 of 0.939 compared to measured data. This performance was decreased to an RMSE of 14.3 N and R2 of 0.296 when applied to an out-of-distribution dataset. Saliency mapping used to interpret model output demonstrated a mechanistic link between typical biophysical tissue changes and model attention. Overall, the end-to-end deep learning approach represents a promising method for rapid, nondestructive evaluation of mechanical properties during food processing and digestion.
•Deep learning accurately predicted compression curves from micro-CT images.•Hardness was accurately extracted from compression curves predicted from 3D images.•Saliency mapping was an effective tool for improving understanding of CNNs.•Hardness predictive quality on external data varied between gastric juice and water.
Use of mindfulness mobile apps has become popular, however, there is little information about subscribers' perceptions of app content and its impact on sleep and mental health. The purpose of this ...study was to survey subscribers to Calm, a popular mindfulness meditation app, to explore perceived improvements in sleep and mental health, evaluate what components of the app were associated with improvements in sleep and mental health, and determine whether improvements differed based on sleep quality. Calm subscribers who had used a sleep-related component in the last 90 days completed a Web-based investigator-developed survey and the Pittsburgh Sleep Quality Index. The survey included questions about using Calm for sleep, sleep disturbances, mental health diagnoses (i.e., anxiety, depression, PTSD) and perceived impacts of the app. Participants reported on the extent to which they felt that using Calm had improved their sleep and mental health. Most participants reported sleep disturbance, and almost half reported a mental health diagnosis. The majority of participants reported that using Calm helped them fall asleep, stay asleep, and get restful sleep. All sleep components were associated with perceived improvements in sleep disturbance. Severity of sleep disturbance moderated relationships between using Calm components and reporting improved sleep. Among subscribers with mental health diagnoses, most reported that Calm helped improve symptoms. Perceived improvement in anxiety and depression was associated with using Calm's meditation components but not Sleep Stories or music/soundscapes. Severity of sleep disturbance did not moderate relationships between using Calm components and reporting mental health improvements. Given the accessibility of app-based meditation, research is needed to evaluate the efficacy of meditation apps to improve sleep disturbance. While some sleep content may be helpful for sleep, more research is needed to test what specific content affects mental health.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Purpose: This study seeks to define immunologic and inflammatory variables associated with persistent post-treatment fatigue in breast
cancer survivors.
Experimental Design: Leukocyte subsets, plasma ...inflammatory markers, and ex vivo proinflammatory cytokine production were assessed in 50 fatigued and nonfatigued breast cancer survivors recruited ≥2 years
after successful primary therapy. Multivariate statistical analyses were used to define a composite immunologic biomarker
of fatigue risk.
Results: Fatigued breast cancer survivors were distinguished from nonfatigued survivors by increased ex vivo monocyte production of interleukin (IL)-6 and tumor necrosis factor-α following lipopolysaccharide stimulation, elevated
plasma IL-1ra and soluble IL-6 receptor (sIL-6R/CD126), decreased monocyte cell-surface IL-6R, and decreased frequencies of
activated T lymphocytes and myeloid dendritic cells in peripheral blood (all P < 0.05). An inverse correlation between sIL-6R and cell-surface IL-6R was consistent with inflammation-mediated shedding
of IL-6R, and in vitro studies confirmed that proinflammatory cytokines induced such shedding. Multivariate linear discriminant function analysis
identified two immunologic markers, the ratio of sIL-6R to monocyte-associated IL-6R and decreased circulating CD69 + T lymphocytes, as highly diagnostic of fatigue ( P = 0.0005), with cross-validation estimates indicating 87% classification accuracy (sensitivity = 0.83; specificity = 0.83).
Conclusion: These results extend links between fatigue and inflammatory markers to show a functional alteration in proinflammatory cytokine
response to lipopolysaccharide and define a prognostic biomarker of behavioral fatigue.
While epigenetic mechanisms such as DNA methylation and histone modification are known to be important for gene suppression, relatively little is still understood about the interplay between these ...systems. The UHRF1 protein can interact with both DNA methylation and repressive chromatin marks, but its primary function in humans has been unclear. To determine what that was, we first established stable UHRF1 knockdowns (KD) in normal, immortalized human fibroblasts using targeting shRNA, since CRISPR knockouts (KO) were lethal. Although these showed a loss of DNA methylation across the whole genome, transcriptional changes were dominated by the activation of genes involved in innate immune signalling, consistent with the presence of viral RNA from retrotransposable elements (REs). We confirmed using mechanistic approaches that 1) REs were demethylated and transcriptionally activated; 2) this was accompanied by activation of interferons and interferon-stimulated genes and 3) the pathway was conserved across other adult cell types. Restoring UHRF1 in either transient or stable KD systems could abrogate RE reactivation and the interferon response. Notably, UHRF1 itself could also re-impose RE suppression independent of DNA methylation, but not if the protein contained point mutations affecting histone 3 with trimethylated lysine 9 (H3K9me3) binding. Our results therefore show for the first time that UHRF1 can act as a key regulator of retrotransposon silencing independent of DNA methylation.
Medicinal plants remain an invaluable source for therapeutics of diseases that affect humanity. Sideritis bilgeriana (Lamiaceae) is medicinal plant used in Turkey folk medicine to reduce inflammation ...and pain, but few studies scientific corroborates its medicinal use so creating a gap between popular use and scientific evidence. Thus, we aimed to evaluate the pharmacological effects of the methanolic extract of S. bilgeriana (MESB) in rodents nociception models and also performed its phytochemical analysis. Firstly, a screening was carried out that enabled the identification of the presence of phenolic compounds and flavonoids. In view of this, a chromatographic method by HPLC-DAD-UV was developed that made it possible to identify chlorogenic acid and its quantification in MESB. MESB-treated mice (MESB 50, 100 and 200 mg/kg, p.o.) reduced mechanical hyperalgesia and myeloperoxidase activity (p < 0.01), and also showed a reduced pain behavior in capsaicin test. In the carrageenan-induced pleurisy test, MESB (100 mg/kg p.o.) significantly reduced the leukocyte (polymorphonuclear) count in the pleural cavity and equally decreased the TNF-α and IL-1β levels (p < 0.001). In the PSNL model, mechanical hyperalgesia was reduced on the first evaluation day and during the 7 days of evaluation compared to the vehicle group (p < 0.001). Thermal hyperalgesia was also reduced 1 h after treatment compared to the vehicle group (p < 0.001) and reversed the loss of force initially displayed by the animals, thus inferring an analgesic effect in the muscle strength test. Analysis of the marrow of these animals showed a decrease in the level of pro-inflammatory cytokine IL-6 (p < 0.001) and factor NF-κB, in relation to the control group (p < 0.05). Moreover, the MESB treatment produced no noticeable side effects, no disturb in motor performance and no signs of gastric or hepatic injury. Together, the results suggests that MESB could be useful to management of inflammation and neuropathic pain mainly by the management of pro-inflammatory mediators (NF-κB, TNF-α, IL-1β and IL-6), so reinforcing its use in popular medicine and corroborating the need for further chemical and pharmacological studies for the species.
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Highlights • Inflammation leads to social withdrawal, but may also lead to approaching close others. • Endotoxin (vs. placebo) led to a greater desire to approach support figures. • Ventral striatum ...activity to support figures was greater in endotoxin participants. • Increases in IL-6 were associated with increased VS to support figures. • Results highlight a more nuanced view of changes in social behavior during sickness.
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