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Experiments in cadavers have demonstrated significant mechanical interactions between constituents of myofascial chains. However, evidence for such force transmission effects is scarce under in vivo conditions. The purpose of this trial was to examine the impact of ankle motion on soft tissue displacement of the dorsal thigh. Eleven healthy active individuals (26.8 ± 4.3 years, six males), in prone position and with the knee extended, underwent passive calf stretches (ankle dorsal extension) imposed by an isokinetic dynamometer. High-resolution ultrasound was used to simultaneously capture the displacement of the semimembranosus muscle, which was quantified by means of cross-correlation analysis. Inactivity of the leg muscles was controlled using surface electromyography (EMG). One participant had to be excluded due to major EMG activity during the experiment. According to a one-sample t test testing the difference to the neutral zero position, ankle dorsal extension induced substantial caudal muscle displacements (5.76 ± 2.67 mm, p < 0.0001). Correlation analysis (Spearman), furthermore, revealed a strong association between maximal dorsal extension and semimembranosus motion (rho = 0.76, p = 0.02). In conclusion, the present trial provides initial in vivo evidence for a mechanical force transmission between serially connected skeletal muscles. This means that local alterations of the mechanical tissue properties may modify flexibility in neighboring (superior or inferior) joints.
The quantified behavioral test - a confirmatory test in the diagnostic process of adult ADHD?
(2020)
The differential diagnosis of attention deficit hyperactivity disorder (ADHD) in adulthood is complicated by comorbid disorders, but also by the overlapping of main symptoms such as inattentiveness, impulsivity, and hyperactivity with other disorders. Neuropsychological tests like continuous performance tests (CPT) try to solve this dilemma by objectively measurable parameters. We investigated in a cohort of n=114 patients presenting to an ADHD outpatient clinic how well a commercially available CPT test (QbTest®) can differentiate between patients with ADHD (n=94) and patients with a disconfirmed ADHD diagnosis (n=20). Both groups showed numerous comorbidities, predominantly depression (27.2% in the ADHD group vs. 45% in the non-ADHD group) and substance-use disorders (18.1% vs. 10%, respectively). Patients with ADHD showed significant higher activity (2.07 ± 1.23) than patients without ADHD (1.34 ± 1.27, dF=112; p=0.019), whereas for the other core parameters, inattention and impulsivity no differences could be found. Reaction time variability has been discussed as a typical marker for inattention in ADHD. Therefore, we investigated how well ex-Gaussian analysis of response time can differentiate between ADHD and other patients, showing, that it does not help to identify patients with ADHD. Even though patients with ADHD showed significantly higher activity, this parameter differed only poorly between patients (accuracy AUC 65% of an ROC-Curve). We conclude that CPTs do not help to identify patients with ADHD in a specialized outpatient clinic. The usability of this test for differentiating between ADHD and other psychiatric disorders is poor and a sophisticated analysis of reaction time did not decisively increase the test accuracy.
Evidence gained from recent studies has generated increasing interest in the role of vitamin D in extraskeletal functions such as inflammation and immunoregulation. Although vitamin D deficiency has been implicated in the pathophysiology of inflammatory diseases including inflammatory bowel disease (IBD), evidence as to whether vitamin D supplementation may cure or prevent chronic disease is inconsistent. Since 25OH-vitamin D (25OHD) has been suggested to be an acute-phase protein, its utility as a vitamin D status marker is therefore questionable. In this study, possible interactions of vitamin D and inflammation were studied in 188 patients with IBD, with high-sensitivity C-reactive protein (hsCRP) levels ≥ 5 mg/dL and/or fecal calprotectin ≥ 250 µg/g defined as biochemical evidence of inflammatory activity. Levels of 25OHD and vitamin D-binding protein (VDBP) were determined by ELISA, and 1,25-dihydroxyvitamin D (1,25OHD) and dihydroxycholecalciferol (24,25OHD) by LC-MS/MS. Free and bioavailable vitamin D levels were calculated with the validated formula of Bikle. Serum 1,25OH2D and vitamin D binding protein (VDBP) levels were shown to differ between the inflammatory and noninflammatory groups: patients with inflammatory disease activity had significantly higher serum concentrations of 1,25OH2D (35.0 (16.4–67.3) vs. 18.5 (1.2–51.0) pg/mL, p < 0.001) and VDBP (351.2 (252.2–530.6) vs. 330.8 (183.5–560.3) mg/dL, p < 0.05) than patients without active inflammation. Serum 24,25OH2D levels were negatively correlated with erythrocyte sedimentation rate (ESR) (−0.155, p = 0.049) while concentrations of serum 1,25OH2D correlated positively with hsCRP (0.157, p = 0.036). Correlations with serum VDBP levels were found for ESR (0.150, p = 0.049), transferrin (0.160, p = 0.037) and hsCRP (0.261, p < 0.001). Levels of serum free and bioavailable 25OHD showed a negative correlation with ESR (−0.165, p = 0.031, −0.205, p < 0.001, respectively) and hsCRP (−0.164, p = 0.032, −0.208, p < 0.001 respectively), and a moderate negative correlation with fecal calprotectin (−0.377, p = 0.028, −0.409, p < 0.016, respectively). Serum total 25OHD concentration was the only vitamin D parameter found to have no specific correlation with any of the inflammatory markers. According to these results, the traditional parameter, total 25OHD, still appears to be the best marker of vitamin D status in patients with inflammatory bowel disease regardless of the presence of inflammation.
Macrophage and tumor cell cross-talk is fundamental for lung tumor progression: we need to talk
(2020)
Regardless of the promising results of certain immune checkpoint blockers, current immunotherapeutics have met a bottleneck concerning response rate, toxicity, and resistance in lung cancer patients. Accumulating evidence forecasts that the crosstalk between tumor and immune cells takes center stage in cancer development by modulating tumor malignancy, immune cell infiltration, and immune evasion in the tumor microenvironment (TME). Cytokines and chemokines secreted by this crosstalk play a major role in cancer development, progression, and therapeutic management. An increased infiltration of Tumor-associated macrophages (TAMs) was observed in most of the human cancers, including lung cancer. In this review, we emphasize the role of cytokines and chemokines in TAM-tumor cell crosstalk in the lung TME. Given the role of cytokines and chemokines in immunomodulation, we propose that TAM-derived cytokines and chemokines govern the cancer-promoting immune responses in the TME and offer a new immunotherapeutic option for lung cancer treatment.
BAG3, a multifunctional HSP70 co-chaperone and anti-apoptotic protein that interacts with the ATPase domain of HSP70 through its C-terminal BAG domain plays a key physiological role in cellular proteostasis. The HSP70/BAG3 complex determines the levels of a large number of selective client proteins by regulating their turnover via the two major protein degradation pathways, i.e. proteasomal degradation and macroautophagy. On the one hand, BAG3 competes with BAG1 for binding to HSP70, thereby preventing the proteasomal degradation of its client proteins. By functionally interacting with HSP70 and LC3, BAG3 also delivers polyubiquitinated proteins to the autophagy pathway. BAG3 exerts a number of key physiological functions, including an involvement in cellular stress responses, proteostasis, cell death regulation, development, and cytoskeletal dynamics. Conversely, aberrant BAG3 function/expression has pathophysiological relevance correlated to cardiomyopathies, neurodegeneration, and cancer. Evidence obtained in recent years underscores the fact that BAG3 drives several key hallmarks of cancer, including cell adhesion, metastasis, angiogenesis, enhanced autophagic activity, and apoptosis inhibition. This review provides a state-of-the-art overview on the role of BAG3 in stress and therapy resistance of cancer, with a particular focus on BAG3-dependent modulation of apoptotic signaling and autophagic/lysosomal activity.
Cancer-induced pain occurs frequently in patients when tumors or their metastases grow in the proximity of nerves. Although this cancer-induced pain states poses an important therapeutical problem, the underlying pathomechanisms are not understood. Here, we implanted adenocarcinoma, fibrosarcoma and melanoma tumor cells in proximity of the sciatic nerve. All three tumor types caused mechanical hypersensitivity, thermal hyposensitivity and neuronal damage. Surprisingly the onset of the hypersensitivity was independent of physical contact of the nerve with the tumors and did not depend on infiltration of cancer cells in the sciatic nerve. However, macrophages and dendritic cells appeared on the outside of the sciatic nerves with the onset of the hypersensitivity. At the same time point downregulation of perineural tight junction proteins was observed, which was later followed by the appearance of microlesions. Fitting to the changes in the epi-/perineurium, a dramatic decrease of triglycerides and acylcarnitines in the sciatic nerves as well as an altered localization and appearance of epineural adipocytes was seen. In summary, the data show an inflammation at the sciatic nerves as well as an increased perineural and epineural permeability. Thus, interventions aiming to suppress inflammatory processes at the sciatic nerve or preserving peri- and epineural integrity may present new approaches for the treatment of tumor-induced pain.
In Germany, a grave labor shortage in the nursing and elderly care sectors has prompted the response of recruiting skilled nursing staff from abroad in recent years. This article analyzes these recruitment practices as forms of “migration management”: German migration policy has changed according to this paradigm to attempt utilitarian control over migration processes and mediate between labor market concerns on the one hand and isolationist, politico-cultural seclusion on the other. Based on original research through interviews and document analysis, we identify four relevant levels of analysis in researching migration management in the context of the recruitment of skilled nurses: (1) Definition of problem areas: How is migration programmatically legitimized as a solution to social problems? (2) Categorization of migration: How are migration processes classified? (3) Change in statehood: How are sites and actors of migration control being privatized and diversified? (4) Technologies: By means of which procedures, legal foundations and political instruments does migration management take place in the everyday? We believe that taking these four foci as points of departure would be beneficial for further inquiries in critical migration research.
Diurnal valley winds frequently form over complex topography, particularly under fair weather conditions, and have a significant impact on the local weather and climate. Since diurnal valley winds result from complex and multi-scale interactions, their representation in numerical weather prediction models is challenging. Better understanding of these local winds based on observations is crucial to improve the accuracy of the forecasts. This study investigates the diurnal evolution of the three-dimensional mean wind structure in a deep Alpine valley, the Rhone valley at Sion, using data from a radar wind profiler and a surface weather station operated continuously from 1 September 2016 to 17 July 2017. In particular, the wind profiler data was analyzed for a subset of days on which fair weather conditions allowed for the full development of thermally driven winds. A pronounced diurnal cycle of the wind speed, as well as a reversal of the wind direction twice per day is documented for altitudes up to about 2 km above ground level (AGL) in the warm season and less than 1 km AGL in winter. The diurnal pattern undergoes significant changes during the course of the year. Particularly during the warm-weather months of May through to September, a low-level wind maximum occurs, where mean maximum up-valley velocities of 8–10 m s−1 are found between 15–16 UTC at altitudes around 200 m AGL. In addition, during nighttime, a down-valley jet with maximum wind speeds of 4–8 m s−1 around 1 km AGL is found. A case study of a three-day period in September 2016 illustrates the occurrence of an elevated layer of cross-valley flow around 1–1.5 km AGL.
An incoming or outgoing hadron in a hard collision with large momentum transfer gets squeezed in the transverse direction to its momentum. In the case of nuclear targets, this leads to the reduced interaction of such hadrons with surrounding nucleons which is known as color transparency (CT). The identification of CT in exclusive processes on nuclear targets is of significant interest not only by itself but also due to the fact that CT is a necessary condition for the applicability of factorization for the description of the corresponding elementary process. In this paper we discuss the semiexclusive processes A(e,e′π+) , A(π−,l−l+) and A(γ,π−p) . Since CT is closely related to hadron formation mechanism, the reduced interaction of ’pre-hadrons’ with nucleons is a common feature of generic high-energy inclusive processes on nuclear targets, such as hadron attenuation in deep inelastic scattering (DIS). We will discuss the novel way to study hadron formation via slow neutron production induced by a hard photon interaction with a nucleus. Finally, the opportunity to study hadron formation effects in heavy-ion collisions in the NICA regime will be considered.
As the biology of mesenchymal stromal cells (MSCs) in patients with non-malignant hematological diseases (NMHD) is poorly understood, in the current study we performed a basic characterization of the phenotype and functional activity of NMHD-MSCs. Bone marrow (BM) of patients with thalassemia major (TM) possessed a significantly higher number of nucleated cells (BM-MNCs)/mL BM than healthy donors (P < 0.0001), which however did not result in a higher number of colony forming units-fibroblast (CFU-F) per milliliter BM. In contrast, from 1 × 106 BM-MNCs of patients with sickle cell disease (SCD) were generated significantly more CFU-Fs than from TM-BM-MNCs (P < 0.013) and control group (P < 0.02). In addition, NMHD-MSCs expressed significantly lower levels of CD146 molecule, demonstrated an equal proliferation potential and differentiated along three lineages (osteoblasts, chondrocytes and adipocytes) as healthy donors’ MSCs, with exception of TM-MSCs which differentiated weakly in adipocytes. In contrast to other NMHD-MSCs and healthy donors’ MSCs, TM-MSCs demonstrated an impaired in vitro immunosuppressive potential, either. Noteworthy, the majority of the immunosuppressive effect of NMHD-MSCs was mediated through prostaglandin-E2 (PGE2), because indomethacin (an inhibitor of PGE2 synthesis) was able to significantly reverse this effect. Our results indicate therefore that NMHD-MSCs, except TM-MSCs, may be used as an autologous cell-based therapy for post-transplant complications such as graft failure, graft-versus-host disease (GvHD) and osteonecrosis.
Accumulating evidence suggests that iron homeostasis is disturbed in tumors. We aimed at clarifying the distribution of iron in renal cell carcinoma (RCC). Considering the pivotal role of macrophages for iron homeostasis and their association with poor clinical outcome, we investigated the role of macrophage-secreted iron for tumor progression by applying a novel chelation approach. We applied flow cytometry and multiplex-immunohistochemistry to detect iron-dependent markers and analyzed iron distribution with atomic absorption spectrometry in patients diagnosed with RCC. We further analyzed the functional significance of iron by applying a novel extracellular chelator using RCC cell lines as well as patient-derived primary cells. The expression of iron-regulated genes was significantly elevated in tumors compared to adjacent healthy tissue. Iron retention was detected in tumor cells, whereas tumor-associated macrophages showed an iron-release phenotype accompanied by enhanced expression of ferroportin. We found increased iron amounts in extracellular fluids, which in turn stimulated tumor cell proliferation and migration. In vitro, macrophage-derived iron showed pro-tumor functions, whereas application of an extracellular chelator blocked these effects. Our study provides new insights in iron distribution and iron-handling in RCC. Chelators that specifically scavenge iron in the extracellular space confirmed the importance of macrophage-secreted iron in promoting tumor growth
Ferlins are multiple-C2-domain proteins involved in Ca2+-triggered membrane dynamics within the secretory, endocytic and lysosomal pathways. In bony vertebrates there are six ferlin genes encoding, in humans, dysferlin, otoferlin, myoferlin, Fer1L5 and 6 and the long noncoding RNA Fer1L4. Mutations in DYSF (dysferlin) can cause a range of muscle diseases with various clinical manifestations collectively known as dysferlinopathies, including limb-girdle muscular dystrophy type 2B (LGMD2B) and Miyoshi myopathy. A mutation in MYOF (myoferlin) was linked to a muscular dystrophy accompanied by cardiomyopathy. Mutations in OTOF (otoferlin) can be the cause of nonsyndromic deafness DFNB9. Dysregulated expression of any human ferlin may be associated with development of cancer. This review provides a detailed description of functions of the vertebrate ferlins with a focus on muscle ferlins and discusses the mechanisms leading to disease development.
Knowledge on the postmortem interval (PMI) of wild boar (Sus scrofa) carcasses is crucial in the event of an outbreak of African swine fever in a wild boar population. Therefore, a thorough understanding of the decomposition process of this species in different microhabitats is necessary. We describe the decomposition process of carcasses exposed in cages. Trial 1 compared a wild boar and a domestic pig (Sus scrofa domesticus) under similar conditions; Trial 2 was performed with three wild boar piglets in the sunlight, shade, or in a wallow, and Trial 3 with two adult wild boar in the sun or shade. The wild boar decomposed more slowly than the domestic pig, which shows that standards derived from forensic studies on domestic pigs are not directly applicable to wild boar. The carcasses exposed to the sun decomposed faster than those in the shade did, and the decomposition of the carcass in the wallow took longest. To assess the state of decomposition, we adapted an existing total body scoring system originally developed for humans. Based on our studies, we propose a checklist tailored to wild boar carcasses found in the field that includes the most important information for a reliable PMI estimation.
Correction to: Scientific Reports https://doi.org/10.1038/srep21848, published online 22 February 2016
This Article contains an error. Among the studied species, the orangutan was erroneously specified as Bornean orangutan Pongo pygmaeus. In fact, the studied individual was a Sumatran orangutan Pongo abelii.
Downsizing of animal communities due to defaunation is prevalent in many ecosystems. Yet, we know little about its consequences for ecosystem functions such as seed dispersal. Here, we use eight seed-dispersal networks sampled across the Andes and simulate how downsizing of avian frugivores impacts structural network robustness and seed dispersal. We use a trait-based modeling framework to quantify the consequences of downsizing-relative to random extinctions-for the number of interactions and secondary plant extinctions (as measures of structural robustness) and for long-distance seed dispersal (as a measure of ecosystem function). We find that downsizing leads to stronger functional than structural losses. For instance, 10% size-structured loss of bird species results in almost 40% decline of long-distance seed dispersal, but in less than 10% of structural loss. Our simulations reveal that measures of the structural robustness of ecological networks underestimate the consequences of animal extinction and downsizing for ecosystem functioning.
The case for corona bonds
(2020)
Corona bonds are feasible and important to preserve the European project. We set out a number of principles that might serve as a blueprint for the European institutions. Importantly, Corona bonds could be issued through a new public law entity and include all the safeguards required for the protection of the fundamental values of the EU. This proposal is pragmatic in the sense that it facilitates the choice European leaders have to make now; necessary to secure the resilience of the European Union. The political risks are significantly higher now than in 2010. The gargantuan challenge of tackling the combined impact of climate change, migration, digitalization, geopolitical shifts, and the spread of autocracy, requires leadership and joint action by the Council and the Eurogroup.
The spreading of the Covid-19 virus causes a reduction in economic activity worldwide and may lead to new risks to financial stability. The authors draw attention to the urgency of the targeted mitigation strategies on the European level and suggest taking coordinated action on the fiscal side to provide liquidity to affected firms in the corporate sector. Otherwise, virus-related cashflow interruptions could lead to a new full-blown banking crisis. Monetary policy measures are unlikely to mitigate cash liquidity shortages at the level of individual firms. Coordinated action at European level is decisive to prevent markets from losing confidence in the resilience of banks, particularly in countries with limited fiscal capacity. In contrast to the euro crisis of 2011, the cause of the current crisis does not lie in the financial markets; therefore, the risk of moral hazard for banks or states is low.
This policy letter adds to the current discussion on how to design a program of government assistance for firms hurt by the Coronavirus crisis. While not pretending to provide a cure-all proposal, the advocated scheme could help to bring funding to firms, even small firms, quickly, without increasing their leverage and default risk. The plan combines outright cash transfers to firms with a temporary, elevated corporate profit tax at the firm level as a form of conditional payback. The implied equity-like payment structure has positive risk-sharing features for firms, without impinging on ownership structures. The proposal has to be implemented at the pan-European level to strengthen Euro area resilience.
Capital in the corona crisis
(2020)
Die Coronakrise und die Eindämmungspolitik der Nationalstaaten hat gravierende wirtschaftliche Folgen. Nicht alle EU-Mitgliedsstaaten sind in gleicher Weise gewappnet und manche werden derzeit heftiger von der Coronakrise getroffen als andere. Eine Möglichkeit, europäische Solidarität zu organisieren, ist die Ausgabe von Gemeinschaftsanleihen, so genannter Corona-Bonds. Dieser Beitrag diskutiert das Für und Wider der Corona-Bonds und ihrer Alternativen: Weder Gemeinschaftsanleihen noch eine Ausweitung des EZB-Engagements sollten das Mittel der Wahl sein. Wir plädieren vielmehr für direkte, auf europäischer Ebene koordinierte Transferzahlungen an bedürftige Mitgliedsstaaten.
The coronavirus has led to a human tragedy, but it need not end up in an economic catastrophe.
In Southern Europe there are signs of a silver lining: the growth rate of the total number of deaths attributed to the coronavirus has been decreasing for weeks in Italy and Spain.
While the effect of the connement measures aim at limiting the spread of the virus is at best uncertain, the economic and social costs of a prolonged lockdown are much less ambiguous and potentially huge. Importantly, these costs can be very unequally distributed.
We argue that it is therefore time to start thinking about how to gradually unlock these countries, and we make some suggestions along this line starting with large-scale testing and continuous re-testing as the most useful pre-condition.
Der Ausnahmezustand
(2020)
Wenn wir die Berechtigung der Maßnahmen im Kampf gegen die Corona-Pandemie unterstellen, dann deshalb, weil wir darauf hoffen, dass sie greifen und etwas bewirken, und zwar in nicht allzu ferner Zukunft. Tun sie es, ist alles gut. Aber was, wenn nicht – und wenn der Zustand, der durch sie eintritt, länger und länger dauert, vielleicht ein Ende auch gar nicht absehbar ist? Dazu drei knappe, aber grundsätzliche Bemerkungen aus der Sicht der Staatstheorie, des Verfassungsrechts und der Rechtsphilosophie.
Human cytomegalovirus (CMV) is a significant cause of morbidity and mortality in patient groups at risk. We have previously shown that the anti-CMV IgG seroprevalence in an urban region of Germany has changed over the last decades. Overall, a decline from 63.7 to 57.25% had been observed between 1988–1997 and 1998–2008 (p < 0,001). Here, we continuously follow the trends to the most recent decade 2009 to 2018. In a retrospective analysis, we determined the seroprevalence of CMV IgG antibodies in our patient cohort, stratified by gender and selected groups at risk (e.g., patients with HIV infection; women of childbearing age). The overall prevalence of anti-CMV IgG non-significantly declined further from 57.25% in 1998–2008 to 56.48% in 2009–2018 (p = 0.881). Looking at gender differences, overall CMV seroprevalence in males declined to 52.82% (from 55.54% in 1998–2008; p = 0.0254), while it non-significantly increased in females to 59.80%. The high seroprevalence in patients with a known HIV infection further increased from 87.46% in 1998–2008 to 92.93% in the current period (p = 0.9999). In women of childbearing age, no significant changes over the last three decades could be observed. The CMV seroprevalence in oncological patients was determined to be 60.64%. Overall, the former significant decline of CMV seroprevalence between the decades 1988–1997 and 1998–2008 in this urban region of Germany slowed down to a non-significant decrease of 0.77% (1998–2008 vs. 2009–2018). This might be an indicator that CMV seroprevalence has reached a plateau.
Sei es ein Stadtteil im Nordend oder ein Park samt dazugehörigem Schlösschen – der Name Holzhausen ist in Frankfurt am Main allgegenwärtig. Die von Holzhausen zählen zu den ältesten Familien Frankfurts. Seit der Mitte des 13. Jahrhunderts prägten ihre Vertreter die Geschicke der Stadt, vor allem im Bereich der Politik, aber auch dem der Kultur. Im frühen 19. Jahrhundert teilte sich die Familie in zwei Linien: Der ältere Zweig verblieb in Frankfurt und starb mit Adolph Freiherr von Holzhausen 1923 aus, die jüngere Linie hingegen ist seit der Mitte des 19. Jahrhunderts in Österreich ansässig. Mit dem Tod Adolph von Holzhausens ging das Erbe des Frankfurter Familienzweigs an die Stadt Frankfurt. Adolph von Holzhausens Vorhaben, schon zu seinen Lebzeiten mit dem Erlös aus dem Verkauf der Grundstücke im Holzhausenviertel den Bau der Universitätsbibliothek zu finanzieren, wurde durch die Hyperinflation vereitelt.
Im nachfolgenden Interview spricht Elena Holzhausen über die heutige Rolle ihrer Familie, deren Bezug zu Frankfurt, die Fortführung der Familientradition und das Mäzenatentum. Elena Holzhausen ist Diözesankonservatorin der Erzdiözese Wien und verheiratet mit Georg Holzhausen. Dessen Bruder, der Dokumentarfilmer Johannes Holzhausen, hatte für die im Jahre 2014 im Historischen Museum Frankfurt gezeigte Ausstellung "Die Holzhausen. Frankfurts älteste Familie" einen Film über das gegenwärtige private Leben der Familie gedreht.
Background: The vascular effects of training under blood flow restriction (BFR) in healthy persons can serve as a model for the exercise mechanism in lower extremity arterial disease (LEAD) patients. Both mechanisms are, inter alia, characterized by lower blood flow in the lower limbs. We aimed to describe and compare the underlying mechanism of exercise-induced effects of disease- and external application-BFR methods. Methods: We completed a narrative focus review after systematic literature research. We included only studies on healthy participants or those with LEAD. Both male and female adults were considered eligible. The target intervention was exercise with a reduced blood flow due to disease or external application. Results: We identified 416 publications. After the application of inclusion and exclusion criteria, 39 manuscripts were included in the vascular adaption part. Major mechanisms involving exercise-mediated benefits in treating LEAD included: inflammatory processes suppression, proinflammatory immune cells, improvement of endothelial function, remodeling of skeletal muscle, and additional vascularization (arteriogenesis). Mechanisms resulting from external BFR application included: increased release of anabolic growth factors, stimulated muscle protein synthesis, higher concentrations of heat shock proteins and nitric oxide synthase, lower levels in myostatin, and stimulation of S6K1. Conclusions: A main difference between the two comparators is the venous blood return, which is restricted in BFR but not in LEAD. Major similarities include the overall ischemic situation, the changes in microRNA (miRNA) expression, and the increased production of NOS with their associated arteriogenesis after training with BFR.
Background: Obesity and depression are both associated with changes in sleep/wake regulation, with potential implications for individualized treatment especially in comorbid individuals suffering from both. However, the associations between obesity, depression, and subjective, questionnaire-based and objective, EEG-based measurements of sleepiness used to assess disturbed sleep/wake regulation in clinical practice are not well known.
Objectives: The study investigates associations between sleep/wake regulation measures based on self-reported subjective questionnaires and EEG-derived measurements of sleep/wake regulation patterns with depression and obesity and how/whether depression and/or obesity affect associations between such self-reported subjective questionnaires and EEG-derived measurements.
Methods: Healthy controls (HC, NHC = 66), normal-weighted depressed (DEP, NDEP = 16), non-depressed obese (OB, NOB = 68), and obese depressed patients (OBDEP, NOBDEP = 43) were included from the OBDEP (Obesity and Depression, University Leipzig, Germany) study. All subjects completed standardized questionnaires related to daytime sleepiness (ESS), sleep quality and sleep duration once as well as questionnaires related to situational sleepiness (KSS, SSS, VAS) before and after a 20 min resting state EEG in eyes-closed condition. EEG-based measurements of objective sleepiness were extracted by the VIGALL algorithm. Associations of subjective sleepiness with objective sleepiness and moderating effects of obesity, depression, and additional confounders were investigated by correlation analyses and regression analyses.
Results: Depressed and non-depressed subgroups differed significantly in most subjective sleepiness measures, while obese and non-obese subgroups only differed significantly in few. Objective sleepiness measures did not differ significantly between the subgroups. Moderating effects of obesity and/or depression on the associations between subjective and objective measures of sleepiness were rarely significant, but associations between subjective and objective measures of sleepiness in the depressed subgroup were systematically weaker when patients comorbidly suffered from obesity than when they did not.
Conclusion: This study provides some evidence that both depression and obesity can affect the association between objective and subjective sleepiness. If confirmed, this insight may have implications for individualized diagnosis and treatment approaches in comorbid depression and obesity.
With increasing distribution of endovascular stroke therapies, transient middle cerebral artery occlusion (tMCAO) in mice now more than ever depicts a relevant patient population with recanalized M1 occlusion. In this case, the desired therapeutic effect of blood flow restauration is accompanied by breakdown of the blood-brain barrier (BBB) and secondary reperfusion injury. The aim of this study was to elucidate short and intermediate-term transcriptional patterns and the involved pathways covering the different cellular players at the neurovascular unit after transient large vessel occlusion. To achieve this, male C57Bl/6J mice were treated according to an intensive post-stroke care protocol after 60 min occlusion of the middle cerebral artery or sham surgery to allow a high survival rate. After 24 h or 7 days, RNA from microvessel fragments from the ipsilateral and the contralateral hemispheres was isolated and used for mRNA sequencing. Bioinformatic analyses allowed us to depict gene expression changes at two timepoints of neurovascular post-stroke injury and regeneration. We validated our dataset by quantitative real time PCR of BBB-associated targets with well-characterized post-stroke dynamics. Hence, this study provides a well-controlled transcriptome dataset of a translationally relevant mouse model 24 h and 7 days after stroke which might help to discover future therapeutic targets in cerebral ischemia/reperfusion injury.
Most mammals rely on the extraction of acoustic information from the environment in order to survive. However, the mechanisms that support sound representation in auditory neural networks involving sensory and association brain areas remain underexplored. In this study, we address the functional connectivity between an auditory region in frontal cortex (the frontal auditory field, FAF) and the auditory cortex (AC) in the bat Carollia perspicillata. The AC is a classic sensory area central for the processing of acoustic information. On the other hand, the FAF belongs to the frontal lobe, a brain region involved in the integration of sensory inputs, modulation of cognitive states, and in the coordination of behavioral outputs. The FAF-AC network was examined in terms of oscillatory coherence (local-field potentials, LFPs), and within an information theoretical framework linking FAF and AC spiking activity. We show that in the absence of acoustic stimulation, simultaneously recorded LFPs from FAF and AC are coherent in low frequencies (1–12 Hz). This “default” coupling was strongest in deep AC layers and was unaltered by acoustic stimulation. However, presenting auditory stimuli did trigger the emergence of coherent auditory-evoked gamma-band activity (>25 Hz) between the FAF and AC. In terms of spiking, our results suggest that FAF and AC engage in distinct coding strategies for representing artificial and natural sounds. Taken together, our findings shed light onto the neuronal coding strategies and functional coupling mechanisms that enable sound representation at the network level in the mammalian brain.
Interspecies hydrogen transfer in anoxic ecosystems is essential for the complete microbial breakdown of organic matter to methane. Acetogenic bacteria are key players in anaerobic food webs and have been considered as prime candidates for hydrogen cycling. We have tested this hypothesis by mutational analysis of the hydrogenase in the model acetogen Acetobacterium woodii. Hydrogenase-deletion mutants no longer grew on H2 + CO2 or organic substrates such as fructose, lactate, or ethanol. Heterotrophic growth could be restored by addition of molecular hydrogen to the culture, indicating that hydrogen is an intermediate in heterotrophic growth. Indeed, hydrogen production from fructose was detected in a stirred-tank reactor. The mutant grew well on organic substrates plus caffeate, an alternative electron acceptor that does not require molecular hydrogen but NADH as reductant. These data are consistent with the notion that molecular hydrogen is produced from organic substrates and then used as reductant for CO2 reduction. Surprisingly, hydrogen cycling in A. woodii is different from the known modes of interspecies or intraspecies hydrogen cycling. Our data are consistent with a novel type of hydrogen cycling that connects an oxidative and reductive metabolic module in one bacterial cell, "intracellular syntrophy."
Working memory (WM) performance varies substantially among individuals but the precise contribution of different WM component processes to these functional limits remains unclear. By analyzing different types of responses in a spatial WM task, we recently demonstrated a functional dissociation between confident and not-confident errors reflecting failures of WM encoding and maintenance, respectively. Here, we use event-related brain potentials to further explore this dissociation. Healthy participants performed a delayed orientation-discrimination task and rated their response confidence for each trial. The encoding-related N2pc component was significantly reduced for confident errors compared to confident correct responses, which is indicative of an encoding failure. In contrast, the maintenance-related contra-lateral delay activity was similar for these response types indicating that in confident error trials, WM representations – potentially the wrong ones – were maintained accurately and with stability throughout the delay interval. However, contra-lateral delay activity measured during the early part of the delay period was decreased for not-confident errors, potentially reflecting compromised maintenance processes. These electrophysiological findings contribute to a refined understanding of the encoding and maintenance processes that contribute to limitations in WM performance and capacity.
"Auch der Verein für Hamburgische Geschichte (VHG) hat lange Zeit vermieden, sein größtes Versagen zu thematisieren", konstatiert der aktuelle Vereinsvorsitzende im Vorwort des Buches. Damit rückt er die Studie explizit in den Kontext der Bewältigungs- und Aufarbeitungsforschung zum Umgang von Ministerien und Parlamenten mit der NS-Vergangenheit, deren Konjunktur noch nicht vorüber ist. Auch von Verlagsseite wird das umfängliche Werk als "erste kritische Detailstudie zur NS-Geschichte eines deutschen Geschichtsvereins" beworben. ...
We extend the canonical income process with persistent and transitory risk to shock distributions with left-skewness and excess kurtosis, to which we refer as higher- order risk. We estimate our extended income process by GMM for household data from the United States. We find countercyclical variance and procyclical skewness of persistent shocks. All shock distributions are highly leptokurtic. The existing tax and transfer system reduces dispersion and left-skewness of shocks. We then show that in a standard incomplete-markets life-cycle model, first, higher-order risk has sizable welfare implications, which depend crucially on risk attitudes of households; second, higher-order risk matters quantitatively for the welfare costs of cyclical idiosyncratic risk; third, higher-order risk has non-trivial implications for the degree of self-insurance against both transitory and persistent shocks.
Dieser Band versammelt die Vorträge einer Tagung der Johannes- Althusius-Gesellschaft e. V., die vom 26.–29.5.2016 in Wittenberg stattfand.
Die umfassende Thematik wurde auf vier Aspekte konzentriert: 1) Religion und Konstitutionalisierung 2) die Bedeutung der Reformation für Rechts- und Staatslehren der frühen Neuzeit, 3) Völkerrecht, 4) Recht, Gehorsam und Religion. Dem folgt auch die Gliederung des Buches. Leider ist die Einleitung des Herausgebers sehr formal. Angesichts einiger sehr anregender neuer Forschungsthesen bzw. -ergebnisse wäre der inhaltliche Schwung der Tagung gleich als Eröffnung gut vermittelbar gewesen. ...
We report the results of a longitudinal intervention with students across five universities in China designed to reduce online consumer debt. Our research design allocates individuals to either a financial literacy treatment, a self-control training program, or a zero-touch control group. Financial education interventions improve test scores on general financial literacy but only marginally affect future online borrowing. Our self-control treatment features detailed tracking of spending and borrowing activity with a third-party app and introspection about individuals' consumption with a counselor. These sessions reduce future online borrowing, delinquency charges, and borrowing for entertainment reasons - and are driven by the male subjects in the sample. Our results suggest that self-regulation can affect financial behavior in e-commerce platforms.
Es ist schon merkwürdig: Für keines der großen Konzilien des Spätmittelalters schien in den letzten Jahren eine Gesamtdarstellung so nah wie im Fall des Pisanum. Dieter Girgensohn und Hélenè Millet legten eine Fülle von Einzelstudien vor, doch keiner der beiden goss sie in die Form eines opus magnum, sieht man von einem Aufsatzband der französischen Kollegin ab. Durch Mona Kirsch erfuhr die Synode 2016 eine zwar viele Facetten erfassende Würdigung im Rahmen einer ritualgeschichtlich grundierten Geschichte des allgemeinen Konzils im Spätmittelalter, zu der für sie aber die auf Pisa folgenden und damit eng verbundenen Versammlungen von Konstanz und Basel nicht gehörten. Und nun erklärt Florian Eßer gleich mehrfach, bei seinem hier anzuzeigenden, immerhin 874-seitigen Werk handele es sich keinesfalls um eine Gesamtdarstellung. Was die Frage aufwirft, wer angesichts einer solch zerklüfteten Landschaft partieller Monumente das finale Wagnis überhaupt noch angehen mag.
Am ehesten wohl Florian Eßer selbst, der eine auf umfassender Kenntnis der ungedruckten wie gedruckten Quellen beruhende und die gesamte Forschung zum Thema rezipierende Studie vorgelegt hat, die weniger als Dissertation – die sie ist – denn fast schon als Habilitationsschrift gelten darf. Nur wünscht man sich und ihm, dass er sich künftig in der Kunst des Kürzens und Streichens übt. Denn hier wird viel in der Sache wohlgemerkt Treffendes derart breit bis in die feinsten Einzelheiten und Verästelungen ausgeführt, ja ausgewalzt, dass dem Autor am Ende dabei offensichtlich selbst nicht mehr so recht wohl war, widmet er sein Opus doch Freundin, Eltern und Freunden, "auch wenn (beziehungsweise weil) sie es vermutlich nie lesen werden" (S. 14). ...
We use data from a German online brokerage and a survey to show that retail investors sharply reduce risk-taking in response to nearby firm bankruptcies, which are not pre- dictive of returns. The effects on trading are spatially highly concentrated, immediate and not persistent. They seem to operate through more pessimistic expected returns and increased risk aversion and do not reflect wealth effects or changes in background risks. Investors learn about bankruptcies through immediate coverage in local newspapers. Our findings suggest that non-informative local experiences that make downside risks of stock investment more salient contribute to idiosyncratic short-term fluctuations in trading.