Körpermasse, sportliche Aktivität und Monozytensubpopulationen bei gesunden Probanden

Hintergrund Kardiovaskuläre Erkrankungen führen in den Industrienationen die Todesursachenstatistiken an und haben aufgrund ihrer hohen Morbidität enorme sozioökonomische Auswirkungen. Bekannt ist, dass ein inflammatorischer Prozess in der Entstehung der Atherosklerose entscheidend ist. Hierbei sind Monozyten von großer Wichtigkeit. Insbesondere die Entdeckung der verschiedenen Monozytensubpopulationen und deren Rolle in der Pathogenese der Atherosklerose führten zu großem wissenschaftlichem Fortschritt. Allerdings liegen nur wenige Untersuchungen zur Bedeutung der Monozytenheterogenität bei gesunden Menschen vor. In der vorliegenden Arbeit erfolgte eine Wiedereinbestellung der Probanden der I-LIKEHOMe- Studie (Inflammation, Lipoprotein Metabolism and Kidney Damage in early atherogenesis - The Homburg Evaluation)[85]. Untersucht wurde bei Gesunden ohne manifeste koronare Herzkrankheit der Zusammenhang zwischen CD14+CD16++-Monozyten und dem Body Mass Index, dem Taille-Hüft-Verhältnis, dem Ausmaß körperlicher Aktivität und Cholesterin beziehungsweise Triglyceriden. Methodik In einer Querschnittsuntersuchung wurden insgesamt 420 Probanden rekrutiert. Diese wurden labormedizinisch und sonographisch durch Messung der Intima-Media-Dicke untersucht. Mittels standardisiertem Fragebogen wurde das kardiovaskuläre Risikoprofil ermittelt. Durch Erhebung von Körpergröße, Körpergewicht, Hüft- und Bauchumfang wurden Body Mass Index und Taille-Hüft-Verhältnis als Parameter der Adipositas berechnet. Per Durchflusszytometrie wurde die immunphänotypische Aufteilung der Monozyten in die drei Subpopulationen klassische CD14++CD16−-Monozyten, intermediäre CD14++CD16+- und nicht-klassische CD14+CD16++-Monozyten erreicht. Ergebnisse Bei Gesunden ohne Vorliegen einer koronarer Herzkrankheit korrelieren CD14+CD16++- Monozyten mit dem Taille-Hüft-Verhältnis (r = 0,284; p < 0,001) als Parameter der Fettverteilung. Eine Assoziation zeigte sich auch zwischen den Zahlen dieser nicht-klassischen Monozyten und BMI-Kategorien als Parameter der Fettmasse (r = 0,315; p < 0,001). Mit zunehmendem Ausmaß körperlicher Aktivität der Studienteilnehmer fielen die Zahlen der CD14+CD16++-Monozyten ab; dies sowohl unter Einbeziehung aller Studienteilnehmer (p = 0,017), als auch unter selektiver Betrachtung der Studienteilnehmer mit BMI > 25 kg/m2 (p = 0,007). Festgestellt wurde ferner eine Korrelation der CD14+CD16++-Monozyten mit den Triglyceriden (r = 0,128; p = 0,009). Dagegen korrelierte HDL negativ mit den Gesamtmonozyten (r = -0,108; p = 0,026) und CD14++CD16−-Monozyten (r = -0,099; p = 0,043). Schlussfolgerungen Der Body Mass Index als Parameter der reinen Körperfettmasse scheint gegenüber der Messung des Taille-Hüft-Verhältnisses, welches eine Abschätzung der Fettverteilung und damit des viszeralen Fettanteils erlaubt, leicht überlegen zu sein. Zur Abschätzung der systemischen Inflammation sollten beide Parameter bestimmt werden. Es ergaben sich weiterhin Hinweise auf einen antiinflammatorischen Effekt regelmäßiger sportlicher Aktivität, auch bei übergewichtigen Individuen. Überdies finden sich Zeichen einer Assoziation zwischen Monozyten und Cholesterin beziehungsweise Triglyceriden, was eine Basis für zukünftige Therapiestrategien zur Prophylaxe atherosklerotischer Erkrankung darstellen könnte.Background Cardiovascular diseases are the leading cause of death in industrial nations and have enormous socioeconomic effects due to their high morbidity. It is known that atherosclerosis is an inflammatory disease. In the pathogenesis of atherosclerosis monocytes are of particular importance. Especially the identification of the different monocyte subpopulations and their role in the pathogenesis of atherosclerosis led to large scientific progress. There are, however, only a few studies on the importance of the monocyte heterogeneity among healthy people. In the present study we reinvited the participants of the I-LIKE-HOMe-Study (Inflammation, Lipoprotein Metabolism and Kidney Damage in early atherogenesis - The Homburg Evaluation)[85]. Among healthy subjects without manifest coronary heart disease we investigated the relationship between CD14+CD16++ monocytes and the body mass index, the waist-hip ratio, the level of physical activity and cholesterol subfractions and triglycerides. Methods In a cross-sectional study a total of 420 subjects was recruited. They were examined by standard laboratory methods and ultrasonic measurement of the intima-media thickness. Furthermore, the cardiovascular risk profile was identified using a standardized questionnaire. Via measurement of body height, body weight, hip and waist circumference, the body mass index and the waist-hip ratio as parameters of obesity were calculated. By flow cytometry the immunophenotypic characterization of monocytes in the three subpopulations classical CD14++CD16− monocytes, intermediate CD14++CD16+ monocytes and non-classical CD14+CD16++ monocytes was performed. Results Among healthy individuals without coronary heart disease CD14+CD16++ monocytes correlated with the waist-hip ratio (r = 0.284, p < 0.001) as an estimator of fat distribution. Furthermore, we found an association between these non-classical monocytes and categories of body mass index as an estimator of general fat mass (r = 0.315, p < 0.001). There was a decrease of numbers of CD14+CD16++ monocytes with increasing level of physical activity; both involving all study participants (p = 0.017) and taking into account only study participants with a BMI > 25 kg/m2 (p = 0.007). In addition, a correlation of CD14+CD16++ monocytes with the triglycerides (r = 0.128, p = 0.009) was found. In contrast, HDL correlated negatively with total monocytes (r = -0.108, p = 0.026) and CD14++CD16− monocytes (r = -0.099, p = 0.043). Conclusion In the differentiated consideration and evaluation of obesity, the assessment of body fat mass via calculation of body mass index appears to be slightly superior to the estimation of body fat localization and thus of visceral fat mass via the waist-hip ratio. For an accurate estimation of systemic inflammation both parameters should be determined. Furthermore, there is evidence of an anti-inflammatory effect of regular physical activity, even among obese individuals. Moreover, in line with other studies, our data suggest a connection between monocytes, cholesterol subfractions and triglycerides, which may constitute a basis for future therapeutic strategies to prevent atherosclerotic disease

Selective Pressure of Temperature on Competition and Cross-Feeding within Denitrifying and Fermentative Microbial Communities

Hanke A, Berg J, Hargesheimer T, Tegetmeyer H, Sharp CE, Strous M. Selective Pressure of Temperature on Competition and Cross-Feeding within Denitrifying and Fermentative Microbial Communities. Front. Microbiol. 2016;6: 1461.In coastal marine sediments, denitrification and fermentation are important processes in the anaerobic decomposition of organic matter. Microbial communities performing these two processes were enriched from tidal marine sediments in replicated, long term chemostat incubations at 10 and 25°C. Whereas denitrification rates at 25°C were more or less stable over time, at 10°C denitrification activity was unstable and could only be sustained either by repeatedly increasing the amount of carbon substrates provided or by repeatedly decreasing the dilution rate. Metagenomic and transcriptomic sequencing was performed at different time points and provisional whole genome sequences (WGS) and gene activities of abundant populations were compared across incubations. These analyses suggested that a temperature of 10°C selected for populations related to Vibrionales/Photobacterium that contributed to both fermentation (via pyruvate/formate lyase) and nitrous oxide reduction. At 25°C, denitrifying populations affiliated with Rhodobacteraceae were more abundant. The latter performed complete denitrification, and may have used carbon substrates produced by fermentative populations (cross-feeding). Overall, our results suggest that a mixture of competition-for substrates between fermentative and denitrifying populations, and for electrons between both pathways active within a single population -, and cross feeding-between fermentative and denitrifying populations-controlled the overall rate of denitrification. Temperature was shown to have a strong selective effect, not only on the populations performing either process, but also on the nature of their ecological interactions. Future research will show whether these results can be extrapolated to the natural environment

Benefits of design practice in fieldwork: How ‘Artesanía para el Bienestar’ emerged in the field as a concept to Improve access to Healthcare in a Mayan Community in Campeche, Mexico

Design, as a discipline can make significant contributions through framing complex issues. This paper explores the values that design practice can offer in the field that cannot be created from a distance with a traditional solution seeking process. This paper presents research showing the benefit of having designers in the field and is based on a project taking place in a Mayan-community in Campeche, Mexico where design thinking was utilized as a tool for achieving sustainable societal change and increasing proactive planning in the community; specifically by generating concepts for improving healthcare. The case study herein presented, ´Artesanía para el Bienestar` (Artistry for Wellbeing) includes fieldwork that took place in the community in 2013. The goal of the fieldwork was to find solutions to increase the community´s access to healthcare and to involve a specific group of stakeholders, artisans, to this process of developing the future of the community. The essence of this paper is not to examine the result of the design process in regard to concepts and solutions created around the topic of healthcare, rather it presents the values and multiple benefits a design process in the field can bring apart from the “end-result” solutions. This case study contributes to the discussion of the role of design, and encourages designers to try new possibilities and directions in design. To achieve sustainable societal change, these aspects of design should be considered and recognized as values in future projects. Research in emergent areas such as social design and social innovation need to grow to support this process. Fuad-Luke (2013) argue that the potential of design research work to lever positive change is significant if it can move beyond the confines of academic discourse, scale up, and find mutually interested partners for these projects to capture the popular imagination

Systemic Delivery of Oncolytic Adenoviruses Targeting Transforming Growth Factor-β Inhibits Established Bone Metastasis in a Prostate Cancer Mouse Model

Abstract We have examined whether Ad.sT?RFc and TAd.sT?RFc, two oncolytic viruses expressing soluble transforming growth factor-? receptor II fused with human Fc (sTGF?RIIFc), can be developed to treat bone metastasis of prostate cancer. Incubation of PC-3 and DU-145 prostate tumor cells with Ad.sT?RFc and TAd.sT?RFc produced sTGF?RIIFc and viral replication; sTGF?RIIFc caused inhibition of TGF-?-mediated SMAD2 and SMAD3 phosphorylation. Ad(E1-).sT?RFc, an E1? adenovirus, produced sTGF?RIIFc but failed to replicate in tumor cells. To examine the antitumor response of adenoviral vectors, PC-3-luc cells were injected into the left heart ventricle of nude mice. On day 9, mice were subjected to whole-body bioluminescence imaging (BLI). Mice bearing hind-limb tumors were administered viral vectors via the tail vein on days 10, 13, and 17 (2.5?1010 viral particles per injection per mouse, each injection in a 0.1-ml volume), and subjected to BLI and X-ray radiography weekly until day 53. Ad.sT?RFc, TAd.sT?RFc, and Ad(E1-).sT?RFc caused significant inhibition of tumor growth; however, Ad.sT?RFc was the most effective among all the vectors. Only Ad.sT?RFc and TAd.sT?RFc inhibited tumor-induced hypercalcemia. Histomorphometric and synchrotron micro-computed tomographic analysis of isolated bones indicated that Ad.sT?RFc induced significant reduction in tumor burden, osteoclast number, and trabecular and cortical bone destruction. These studies suggest that Ad.sT?RFc and TAd.sT?RFc can be developed as potential new therapies for prostate cancer bone metastasis.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/98454/1/hum%2E2012%2E040.pd

Pandemic gardening:A narrative review, vignettes and implications for future research

There is a significant amount of evidence highlighting the health, wellbeing and social benefits of gardening during previous periods of crises. These benefits were also evident during the COVID-19 pandemic. This paper presents a narrative review exploring gardening during the early stages of the COVID-19 pandemic to understand the different forms of gardening that took place during this crisis and key elements of this activity. Research about gardening during the pandemic focused on food (in)security and disrupted food systems, the health and wellbeing benefits of gardening, and the social dimensions of gardening. We offer three vignettes of our own research to highlight key insights from local, national and international perspectives of gardening during the pandemic. The paper's conclusion outlines how researchers, policy makers and public health practitioners can harness what has been learned from gardening during the pandemic to ensure these benefits are more widely available and do not exacerbate already entrenched health inequalities in society.</p

T-lymphocyte subsets in liver tissues of patients with primary biliary cirrhosis (PBC), patients with primary sclerosing cholangitis (PSC), and normal controls

T lymphocytes infiltrating hepatic tissues were typed and enumerated in liver biopsies of patients with primary biliary cirrhosis (PBC), patients with primary sclerosing cholangitis (PSC), and normal controls using monoclonal antibodies and the avidin-biotin-immunoperoxidase technique. The peripheral blood mononuclear cells were studied also by flow cytometry. In PBC, T lymphocytes were decreased (P<0.001) in the blood [absolute number was 426±200 (SE) vs 1351±416 in 15 controls], as was the helper/suppressor (T4/T8) ratio (1.0±0.1 vs normal 2.3±0.3). T lymphocytes were the most numerous mononuclear cells infiltrating portal areas of PBC livers: 749±93/5 high-power fields (HPF) in PBC vs 98±15/5 HPF (P<0.01) in controls. The T4/T8 ratios varied from 0.9 to 2.3 (mean, 1.8±0.1) in the portal triads (normal mean, 1.6±0.1), with the T4+ cells accounting for more than 75% of infiltrating T cells. In contrast, the mean T4/T8 ratio in portal triads of PSC was reduced (1.0±0.3) due to a significant increase (P<0.001) in the number of T8+ cells. The T cells around and in the walls of bile ducts in PBC were mostly T8+, and the T4/T8 ratio was 0.8±0.2. No T8+ cells were seen in this location in PSC and normal livers. Few mononuclear cells were present in hepatic lobules. Subtyping of T lymphocytes in liver tissues of patients with PBC and PSC may be helpful in the differential pathologic diagnosis. In patients with advanced PBC, a decrease in T4+ cells in the blood appeared to be accompanied by their accumulation in the portal triads. In contrast, T8+ cells accumulated preferentially around bile ducts. © 1984 Plenum Publishing Corporation

Older adults’ coping strategies during the COVID-19 pandemic – a longitudinal mixed-methods study

IntroductionOlder age is a main risk factor for severe COVID-19. In 2020, a broad political debate was initiated as to what extent older adults need special protection and isolation to minimize their risk for SARS-CoV-2 infection. However, isolation might also have indirect negative psychological (e.g., loneliness, stress, fear, anxiety, depression) or physical (e.g., lack of exercise, missing medical visits) consequences depending on individual strategies and personality traits to cope longitudinally with this crisis.MethodsTo examine the impact of individuals’ coping with the pandemic on mental health, a large sample of 880 older adults of the prospective longitudinal cohort TREND study were surveyed six times about their individual coping strategies in the COVID-19 pandemic between May 2020 (05/2020: Mage = 72.1, SDage = 6.4, Range: 58–91 years) and November 2022 in an open response format. The relevant survey question was: “What was helpful for you to get through the last months despite the COVID-19 pandemic? E.g., phone calls, going for a walk, or others.”Results and DiscussionIn total, we obtained 4,561 records containing 20,578 text passages that were coded and assigned to 427 distinct categories on seven levels based on qualitative content analysis using MAXQDA. The results allow new insights into the impact of personal prerequisites (e.g., value beliefs, living conditions), the general evaluation of the pandemic (e.g., positive, irrelevant, stressful) as well as the applied coping strategies (e.g., cognitive, emotional- or problem-focused) to deal with the COVID-19 pandemic by using an adapted Lazarus stress model. Throughout the pandemic emotional-focused as well as problem-focused strategies were the main coping strategies, whereas general beliefs, general living conditions and the evaluation were mentioned less frequently

Pan-Cancer Analysis of lncRNA Regulation Supports Their Targeting of Cancer Genes in Each Tumor Context

Long noncoding RNAs (lncRNAs) are commonly dys-regulated in tumors, but only a handful are known toplay pathophysiological roles in cancer. We inferredlncRNAs that dysregulate cancer pathways, onco-genes, and tumor suppressors (cancer genes) bymodeling their effects on the activity of transcriptionfactors, RNA-binding proteins, and microRNAs in5,185 TCGA tumors and 1,019 ENCODE assays.Our predictions included hundreds of candidateonco- and tumor-suppressor lncRNAs (cancerlncRNAs) whose somatic alterations account for thedysregulation of dozens of cancer genes and path-ways in each of 14 tumor contexts. To demonstrateproof of concept, we showed that perturbations tar-geting OIP5-AS1 (an inferred tumor suppressor) andTUG1 and WT1-AS (inferred onco-lncRNAs) dysre-gulated cancer genes and altered proliferation ofbreast and gynecologic cancer cells. Our analysis in-dicates that, although most lncRNAs are dysregu-lated in a tumor-specific manner, some, includingOIP5-AS1, TUG1, NEAT1, MEG3, and TSIX, synergis-tically dysregulate cancer pathways in multiple tumorcontexts

Pan-cancer Alterations of the MYC Oncogene and Its Proximal Network across the Cancer Genome Atlas

Although theMYConcogene has been implicated incancer, a systematic assessment of alterations ofMYC, related transcription factors, and co-regulatoryproteins, forming the proximal MYC network (PMN),across human cancers is lacking. Using computa-tional approaches, we define genomic and proteo-mic features associated with MYC and the PMNacross the 33 cancers of The Cancer Genome Atlas.Pan-cancer, 28% of all samples had at least one ofthe MYC paralogs amplified. In contrast, the MYCantagonists MGA and MNT were the most frequentlymutated or deleted members, proposing a roleas tumor suppressors.MYCalterations were mutu-ally exclusive withPIK3CA,PTEN,APC,orBRAFalterations, suggesting that MYC is a distinct onco-genic driver. Expression analysis revealed MYC-associated pathways in tumor subtypes, such asimmune response and growth factor signaling; chro-matin, translation, and DNA replication/repair wereconserved pan-cancer. This analysis reveals insightsinto MYC biology and is a reference for biomarkersand therapeutics for cancers with alterations ofMYC or the PMN