A lesson for cancer research : placental microarray gene analysis in preeclampsia

Tumor progression and pregnancy share many common features, such as immune tolerance and invasion. The invasion of trophoblasts in the placenta into the uterine wall is essential for fetal development, and is thus precisely regulated. Its deregulation has been implicated in preeclampsia, a leading cause for maternal and perinatal mortality and morbidity. Pathogenesis of preeclampsia remains to be defined. Microarray-based gene profiling has been widely used for identifying genes responsible for preeclampsia. In this review, we have summarized the recent data from the microarray studies with preeclamptic placentas. Despite the complex of gene signatures, suggestive of the heterogeneity of preeclampsia, these studies identified a number of differentially expressed genes associated with preeclampsia. Interestingly, most of them have been reported to be tightly involved in tumor progression. We have discussed these interesting genes and analyzed their potential molecular functions in preeclampsia, compared with their roles in malignancy development. Further investigations are warranted to explore the involvement in molecular network of each identified gene, which may provide not only novel strategies for prevention and therapy for preeclampsia but also a better understanding of cancer cells. The trophoblastic cells, with their capacity for proliferation and differentiation, apoptosis and survival, migration, angiogenesis and immune modulation by exploiting similar molecular pathways, make them a compelling model for cancer research

Life Cycle Management of Public Estates with a Focus on Universities and Research Institutes

Wissenschaftseinrichtungen und Hochschulen stehen in den nächsten Jahren in Folge der Föderalismusreform und der Abschaffung des Hochschulbauförderungsgesetzes vor besonderen Herausforderungen, die nur unter effizienter Ausnutzung aller vorhandenen Ressourcen zu meistern sind. Insbesondere der kummulierte Bau-, Sanierungs- und damit Finanzierungsbedarf führt zu der Erkenntnis, dass immobilienbezogene Entscheidungen langfristig über den gesamten Lebenszyklus zu treffen sind, damit ein schleichender Wertverlust vermieden wird. Die Arbeit beschäftigt sich mit den anstehenden Veränderungsprozessen im Hinblick auf ein lebenszyklusorientiertes Liegenschaftsmanagement. Ausgehend von den Rahmenbedingungen werden Handlungs- und Gestaltungshilfen für die Praxis entwickelt, die spezifisch für Hochschulen, Wissenschaftseinrichtungen und Studentenwerke anwendbar sind. Dabei fließen die Erfahrungen aus der Untersuchung konkreter Pilotprojekte in die Untersuchung ein. In der Arbeit wird ein Datenmodell entwickelt, das Entscheidungen im lebenszyklusorientierten Liegenschaftsmanagement bei Neu-, Umbau- und Sanierungs¬maßnahmen und die Wahl von Beschaffungsvarianten unterstützt. Die Arbeit befasst sich mit drei Untersuchungsschwerpunkten: 1. Immobilienportfolioebene: Lebenszyklusorientierte Betrachtung des Gesamtbestandes an Liegenschaften, 2. Projektebene: Analyse und Bewertung lebenszyklusorientierter Vertrags- und Organisationsformen mit privater Beteiligung, 3. Datenebene: Analyse vorhandener Daten und Kennzahlen für eine Lebens-zyklusbetrachtung; Erarbeitung eines Datenmodells zum Kostencontrolling.Due to the federalistic reform (Föderalismusreform) and the abolition of the higher education building aid law (Hochschulbauförderungsgesetz HBFG), and against the background of a massive reconstruction backlog, the German research institutes and higher education institutes (universities and colleges) face numerous organisational and economic changes and a range of new challenges. Hence the increase in the competition for financial resources and students and calls for more efficiency in the allocation of resources. Given the current debate on the transformation process the German higher education sector faces, the overall aim is to identify compulsory change processes in the estate management. In this context, the composition seeks to give a comprehensive but concise overview of estate management in the higher education sector. In addition, the report aims to develop a data stucture model which contains the crucial data elements needed to support a robust value-for-money analysis, subsequent decisions for the form of procurement as well as potentially succeeding construction, reconstruction, conversion and/or operation processes. The report is divided into three major parts. 1. Real Estate Portfolio: structures and characteristics of estate management in the German higher education sector, 2. Specific Projects: concentrates on specific PPP projects of higher education institutions, 3. Data Structure: analysis and evaluation of existing data and operating figures for life cycle estate management; developing data structure model for controlling

Pressure Pain Thresholds and Central Sensitization in Relation to Psychosocial Predictors of Chronicity in Low Back Pain

(1) Background: Peripheral, as well as central, sensitization have been described in chronic low back pain (cLBP). The purpose of this study is to investigate the influence of psychosocial factors on the development of central sensitization. (2) Methods: This prospective study investigated local and peripheral pressure pain thresholds and their dependence on psychosocial risk factors in patients with cLBP receiving inpatient multimodal pain therapy. Psychosocial factors were assessed using the Örebro Musculoskeletal Pain Screening Questionnaire (ÖMPSQ). (3) Results: A total of 90 patients were included in the study, 61 (75.4% women, 24.6% men) of whom had significant psychosocial risk factors. The control group consisted of 29 patients (62.1% women, 37.9% men). At baseline, patients with psychosocial risk factors showed significantly lower local and peripheral pressure pain thresholds, suggesting central sensitization, compared to the control group. Sleep quality, measured by the Pittsburgh Sleep Quality Index (PSQI), was also correlated with altered PPTs. After multimodal therapy, all participants reported increased local pain thresholds compared to at admission, independent of psychosocial chronification factors. (4) Conclusions: Psychosocial chronicity factors measured using the ÖMPSQ have a significant influence on pain sensitization in cLBP. A 14-day multimodal pain therapy increased local, but not peripheral, pressure pain thresholds

Neck muscle function in violinists/violists with and without neck pain

Neck pain is associated with changes in neuromuscular control of cervical muscles. Violin and viola playing requires good function of the flexor muscles to stabilize the instrument. This study investigated the flexor muscle behaviour in violin/viola players with and without neck pain using the craniocervical flexion test (CCFT). In total, 12 violin/viola players with neck pain, 21 violin/viola players without neck pain in the preceding 12 weeks and 21 pain-free non-musicians were included. Activity of the sternocleidomastoid muscles (SCM) was measured with surface electromyography (EMG) during the CCFT. Violin/viola players with neck pain displayed greater normalised SCM EMG amplitudes during CCFT than the pain-free musicians and non-musicians (P

Synthesis, biological evaluation and molecular modelling of new potent clickable analogues of 5-OP-RU for their use as chemical probes for the study of MAIT cell biology

International audienceMAIT cells are preset αβ T lymphocytes that recognize a series of microbial antigens exclusively derived from the riboflavin biosynthesis pathway, which is present in most bacteria. The most active known antigen is unstable 5-(2-oxopropylideneamino)-6-(d-ribitylamino)uracil (5-OP-RU) which is stabilized when bound and presented to MAIT cells by MHC-related protein 1 (MR1). Here we describe the chemical synthesis and biological evaluation of new chemical probes for the study of MAIT cell biology. The two probes were ethinyl functionalized analogues of 5-OP-RU able to react through CuAAC also called "click chemistry". The molecules up-regulated more MR1 than 5-OP-RU and they efficiently activated iVα19 Vβ8 TCR transgenic murine MAIT cells but not iVα19 TCRα transgenic MAIT cells indicating a surprisingly strong impact of the TRCβ chain. Moreover, the use of these molecules as chemical probes was validated in vitro by efficient and selective binding to MR1 revealed via fluorescence microscopy. This study was also complemented by molecular modelling investigation of the probes and the binary/ternary complexes they form with MR1 and the TCR. These new probes will be crucial to delineate the dynamics of 5-OP-RU at the cellular or whole organism level and to identify the cells presenting 5-OP-RU to MAIT cells in vivo

Effects of Different Forms of Sensorimotor Training on Postural Control and Functional Status in Patients with Chronic Low Back Pain

The aim of this study was to compare three sensorimotor training forms in patients with chronic low back pain to determine their effects on the reduction of pain-related impairment and changes in posturography. Over two weeks, during the multimodal pain therapy (MMPT) period, six sessions of sensorimotor physiotherapy or training in the Galileo® or Posturomed® (n = 25 per group) were performed. A significant reduction in pain-related impairment after the intervention phase was shown across all groups (time effect: p < 0.001; ηp2 = 0.415). There was no change in postural stability (time effect: p = 0.666; ηp2 = 0.003), but there was a significant improvement in the peripheral vestibular system (time effect: p = 0.014; ηp2 = 0.081). An interaction effect was calculated for the forefoot-hindfoot ratio (p = 0.014; ηp2 = 0.111). Only the Posturomed® group showed an improvement in anterior-posterior weight distribution (heel load: 47% vs. 49%). These findings suggest that these forms of sensorimotor training in the context of MMPT are suitable for reducing pain-related impairment. Posturography demonstrated stimulation of a subsystem, but no improvement in postural stability

X-ray structure of the orphan nuclear receptor RORβ ligand-binding domain in the active conformation

The retinoic acid-related orphan receptor β (RORβ) exhibits a highly restricted neuronal-specific expression pattern in brain, retina and pineal gland. So far, neither a natural RORβ target gene nor a functional ligand have been identified, and the physiological role of the receptor is not well understood. We present the crystal structure of the ligand-binding domain (LBD) of RORβ containing a bound stearate ligand and complexed with a coactivator peptide. In the crystal, the monomeric LBD adopts the canonical agonist-bound form. The fatty acid ligand–coactivator peptide combined action stabilizes the transcriptionally active conformation. The large ligand-binding pocket is strictly hydrophobic on the AF-2 side and more polar on the β-sheet side where the carboxylate group of the ligand binds. Site-directed mutagenesis experiments validate the significance of the present structure. Homology modeling of the other isotypes will help to design isotype-selective agonists and antagonists that can be used to characterize the physiological functions of RORs. In addition, our crystallization strategy can be extended to other orphan nuclear receptors, providing a powerful tool to delineate their functions

Longitudinal Clinical Features of Post-COVID-19 Patients—Symptoms, Fatigue and Physical Function at 3- and 6-Month Follow-Up

Post-COVID-19 syndrome (PCS) has been described as ‘the pandemic after the pandemic’ with more than 65 million people worldwide being affected. The enormous range of symptoms makes both diagnosis complex and treatment difficult. In a post-COVID rehabilitation outpatient clinic, 184 patients, mostly non-hospitalized, received a comprehensive, interdisciplinary diagnostic assessment with fixed follow-up appointments. At baseline, three in four patients reported more than 10 symptoms, the most frequent symptoms were fatigue (84.9%), decreased physical capacity (83.0%), tiredness (81.1%), poor concentration (73.6%), sleeping problems (66.7%) and shortness of breath (67.3%). Abnormalities were found in the mean values of scores for fatigue (FAS = 34.3), cognition (MoCA = 25.5), psychological alterations (anxiety, depression, post-traumatic stress disorder), limitation of lung function (CAT) and severity scores for PCS (PCFS, MCRS). Clinical abnormalities were found in elevated values of heart rate, breathing rate at rest, blood pressure and NT-proBNP levels. As the frequency of the described symptoms decreases only slowly but most often significantly over the course, it is important to monitor the patients over a longer period of time. Many of them suffer from an immense symptom burden, often without pre-existing clinical correlates. Our results show a clear association with objectifiable assessments and tests as well as pronounced symptoms

Neuromodulation through brain stimulation-assisted cognitive training in patients with post-COVID-19 cognitive impairment (Neuromod-COV): study protocol for a PROBE phase IIb trial

IntroductionA substantial number of patients diagnosed with COVID-19 experience long-term persistent symptoms. First evidence suggests that long-term symptoms develop largely independently of disease severity and include, among others, cognitive impairment. For these symptoms, there are currently no validated therapeutic approaches available. Cognitive training interventions are a promising approach to counteract cognitive impairment. Combining training with concurrent transcranial direct current stimulation (tDCS) may further increase and sustain behavioural training effects. Here, we aim to examine the effects of cognitive training alone or in combination with tDCS on cognitive performance, quality of life and mental health in patients with post-COVID-19 subjective or objective cognitive impairments.Methods and analysisThis study protocol describes a prospective randomised open endpoint-blinded trial. Patients with post-COVID-19 cognitive impairment will either participate in a 3-week cognitive training or in a defined muscle relaxation training (open-label interventions). Irrespective of their primary intervention, half of the cognitive training group will additionally receive anodal tDCS, all other patients will receive sham tDCS (double-blinded, secondary intervention). The primary outcome will be improvement of working memory performance, operationalised by an n-back task, at the postintervention assessment. Secondary outcomes will include performance on trained and untrained tasks and measures of health-related quality of life at postassessment and follow-up assessments (1 month after the end of the trainings).Ethics and disseminationEthical approval was granted by the Ethics Committee of the University Medicine Greifswald (number: BB 066/21). Results will be available through publications in peer-reviewed journals and presentations at national and international conferences.Trial registration numberNCT04944147