Upregulation of Wnt regulators is associated with low bone mass In elderly Portuguese men and women

Bone biomarkers are chemical substances produced during the bone remodelling pro-cess that can provide beneficial information concerning bone metabolism. Recently, some studies highlighted the importance of Wnt signalling, a crucial pathway for osteo-blast differentiation and a master bone mass regulator. In fact, serum levels of Dkk1 and SOST, which are negative regulators of Wnt signalling, increase with age and are associ-ated with bone mass loss. Previous studies from the CEDOC group showed that, in fra-gility fracture patients, osteoblast terminal differentiation is impaired, which is associated with bone mechanical fragility. Therefore, it was hypothesized that serum Wnt regulators are associated to bone fragility and can constitute new markers for osteoporosis treatment decision. In this dissertation, the association between bone gene expression of markers of osteoblast and osteoclast differentiation and of Wnt pathway regulators (Dkk1, Dkk2, SOST, WIF1 and sFRP1) with bone mineral density was analysed. Furthermore, the association between serum levels of bone biomarkers and Wnt regulators and bone mineral density was analysed as well. A set of 128 patients submitted to hip arthroplasty, aged above 40 years old, were evaluated from a clinical database. Linear regression analysis was performed to assess the above-mentioned associations. Associations within estimators were conducted to compute missing values. Stepwise regression was used with the Backward elimination process and bootstrapping was used to externally validate the models. Besides the bone biomarkers, four variables were included to the models, namely sex, rheumatoid arthritis, corticoid use and secondary osteoporosis. Positive correlations were found between serum levels of Wnt regulators (P1NP, SOST and Dkk1) and BMD. With respect to the genetic expression of bone biomarkers, Dkk2 and sFRP1 were negatively associated with BMD, whereas Lrp6 and WIF1 were positively correlated. These results demonstrate that an upregulation of bone gene expression of Wnt regulators, namely some of the Wnt inhibitors, is associated with low bone mass. The low number of patients is a limitation and further studies need to be conducted in larger populations and with the inclusion of more bone biomarkers. This dissertation was conducted under the project ARIBOS, funded by the Portuguese Society of Rheumatology

Koncepcja stare decisis w systemie prawa niemieckiego – niespójna systemowo koncepcja posiadająca wysoką realną wartość

It is worth mentioning that the German legal system is based on the codified law. This system lacks in stare decisis and precedents in general, which – in principle – does not raise doubts. The role of precedent in the decisional process is relative and dependent on the question as to whether the case may be resolved pursuant to a legal act. In that case, precedents would not play any or almost any role at all. However, the role of precedents increases, when there is a lack of appropriate legal rights, or if legal rights require interpretation. It should be emphasised that stare decisis understood as a formally binding precedent refers only to rulings issued by the Federal Constitutional Court, whereas precedents of higher courts have a significant meaning to everyday judicial practice in Germany, despite the fact that they are not formally binding.Należy wskazać, że niemiecki system prawa opiera się na prawie skodyfikowanym. W systemie tym brak stare decisis oraz precedensów w ogóle, co do zasady nie budzi to wątpliwości. Rola precedensu w procesie decyzyjnym sądów jest względna i zależy od tego, czy sprawa może zostać rozstrzygnięta zgodnie z brzmieniem ustawy. Wówczas precedensy nie będą odgrywać żadnej roli lub będzie ona marginalna. W przypadku, gdy brak jest odpowiedniego prawa ustawowego lub jeśli ustawowe prawo wymaga interpretacji, rola precedensów wzrasta. Należy podkreślić, że stare decisis w sensie formalnie wiążącego precedensu odnosi się tylko do orzeczeń Federalnego Trybunału Konstytucyjnego. Natomiast precedensy wyższych sądów, choć nie są formalnie wiążące, mają istotne znaczenie dla codziennej praktyki prawniczej w Niemczech

Low muscle strength and increased arterial stiffness go hand in hand

Low handgrip strength and increased arterial stiffness are both associated with poor health outcomes, but evidence on the relationship between handgrip strength and arterial stiffness is limited. In this cross-sectional analysis of combined baseline datasets from the LipidCardio and Berlin Aging Study II cohorts we aimed to examine whether handgrip strength (HGS) is associated with arterial stiffness. 1511 participants with a median age of 68.56 (IQR 63.13-73.08) years were included. Arterial stiffness was assessed by aortal pulse wave velocity (PWV) with the Mobil-O-Graph device. Handgrip strength was assessed with a handheld dynamometer.The mean HGS was 39.05 +/- 9.07 kg in men and 26.20 +/- 7.47 kg in women. According to multivariable linear regression analysis per 5 kg decrease in handgrip strength there was a mean increase in PWV of 0.08 m/s after adjustment for the confounders age, sex, coronary artery disease, systolic blood pressure, body mass index, cohort, and smoking. Thus, there was evidence that low handgrip strength and increased arterial stiffness go hand in hand. Arterial stiffness can possibly create the missing link between low handgrip strength and increased cardiovascular morbidity and mortality. Causality and direction of causality remain to be determined

Hyperlipidemias in elderly patients: results from the Berlin Aging Study II (BASEII), a cross-sectional study

Background: Hyperlipidemias are common and the last decades have seen substantially growing evidence of their causative role in the development of atherosclerosis and subsequent cardiovascular diseases. Since hyperlipidemias usually do not cause direct clinical symptoms, they often remain undiagnosed until a serious cardiovascular event occurs. Especially for LDL-hypercholesteremia, there are well-established treatment options available to prevent the occurrence of atherosclerosis. However, there is a lack of knowledge regarding the proper treatment of elderly patients. The goal of this study was to assess the prevalence of hyperlipidemia in a group of young and a group of elderly community-dwelling participants and to determine to what extent treatment of hyperlipidemia should be initiated or required. Methods: Crossectional data from a total of 2151 subjects (1657 in the elderly group, mean age 69, and 494 in the young group (control group), mean age 29) of the Berlin Aging Study II (BASE-II) were available. Medical history was assessed and recorded by trained physicians and prevalence of lipid disorders was determined with laboratory tests, including a lipid-profile. Results: A large proportion of subjects (39%) were unaware of an existing lipid disorder. The prevalence of hyperlipidemia was more frequent in the elderly group (76%) compared to the young group (41%). Hypercholesterolemia was the most common diagnosed disorder (64%), followed by hyperlipoproteinemia(a) (18%), hypertriglyceridemia (7%) and combined hyperlipoproteinaemia (5%). Only a minority of this cohort was treated with lipid-lowering medication (17%) and of those treatment targets according to ESC guidelines were reached only in 16.5 %. Conclusions: Hyperlipidemias appear underdiagnosed and undertreated. As the prevalence of these disorders increases with age and with regard to their role as a major modifiable risk factor for cardiovascular disease it seems to be advisable to aim for more consistent and sustainable screening and treatment of these common disorders. Trial registration: BASE-II registered with the clinical trial registry Deutsches Register Klinischer Studien (DRKS00009277)

Meta-Studie: Covid-19-Pandemie und betriebliche Anpassungsmaßnahmen: Begleitforschung zur Arbeitsweltberichterstattung im Auftrag des BMAS, Bd. 4

Die vorliegende Studie fasst den Stand der Erkenntnisse zu den Auswirkungen der Covid-19-Pandemie auf Betriebe und Beschäftigte sowie zu den betrieblichen Anpassungsmaßnahmen zusammen. Hierzu wurde eine Vielzahl von Studien und zugrundeliegenden Erhebungen erfasst und ausgewertet. Die einbezogenen Studien basieren auf Primärbefragungen bei Betrieben, Beschäftigten oder anderen Personen, die in Deutschland durchgeführt wurden. In einem weiteren Arbeitsschritt wird der Forschungsstand im Hinblick auf Vollständigkeit bzw. Forschungslücken bewertet.This study summarizes the current state of knowledge on the impact of the Covid 19 pandemic on companies and employees and on companies’ adaptation measures. For this purpose, a large number of studies and surveys were recorded and analyzed. The studies included are based on primary surveys of companies, employees or other persons conducted in Germany. In a further step, the current state of research is evaluated with regard to completeness and research gaps

Prospektion einer Villa rustica bei Wederath, Flur Kleinicher Berg (Gde. Morbach, Kr. Bernkastel-Wittlich, Rheinland-Pfalz)

Prospektionen der Universität Leipzig im Umkreis des römischen vicus Belginum weisen bei Wederath, Flur Kleinicher Berg (Gde. Morbach, Kr. Bernkastel-Wittlich, Rheinland Pfalz) eine mutmaßliche villa rustica hin. Diese lag auf einem kleinen Plateau außerhalb der Begehungsfläche. Das Fundmaterial besteht vorwiegend aus Ziegeln (Dach- und Fußbodenziegel) und relativ wenig Keramik. Die bestimmbare römische Keramik datiert in das 2. bis 4. Jh. n. Chr. Bemerkenswert ist der Fund mehrerer Scherben der Hunsrück-Eifel-Kultur. Sie könnten einen Hinweis auf eine Besiedlung des Plateaus seit der Mitte des 1. Jahrtausends v. Chr. darstellen. Nur wenige hundert Meter entfernt befindet sich das große Hügelgräberfeld „Götzeroth“ der Hunsrück- Eifel-Kultur.Archaeological prospections by the University of Leipzig in the surroundings of the Roman vicus Belginum revealed near Wederath (Rhenania-Palatinate, Germany) a probable villa rustica. Mostly bricks (tegulae, imbrices and floor tiles) and only a small amount of ceramics were found. The Roman ceramics are dating mostly into the 2nd to 4th cent. AD. Remarkable are the finds of some ceramic sherds of the Hunsrück-Eifel-Culture. They could indicate settlement activity at the site since the mid of the first millennium BC. The extended tumulus cemetery “Götzeroth” is located some hundred meters to the east

Increased cancer prevalence in peripartum cardiomyopathy

Objectives This study was designed to analyze the prevalence and potential genetic basis of cancer and heart failure in peripartum cardiomyopathy (PPCM). Background PPCM manifests as heart failure late in pregnancy or postpartum in women without previous heart disease. Methods Clinical history and cancer prevalence were evaluated in a cohort of 236 PPCM patients from Germany and Sweden. Exome sequencing assessed variants in 133 genes associated with cancer predisposition syndromes (CPS) and in 115 genes associated with dilated/hypertrophic cardiomyopathy (DCM/HCM) in 14 PPCM patients with a history of cancer, and in 6 PPCM patients without a history of cancer. Results The prevalence of cancer was 16-fold higher (8.9%, 21 of 236 patients) in PPCM patients compared to age-matched women (German cancer registry, Robert-Koch-Institute: 0.59%; p < 0.001). Cancer before PPCM occurred in 12 of 21 patients of whom 11 obtained cardiotoxic cancer therapies. Of those, 17% fully recovered cardiac function by 7 ± 2 months of follow-up compared to 55% of PPCM patients without cancer (p = 0.015). Cancer occurred after PPCM in 10 of 21 patients; 80% had left ventricular ejection fraction of ≥50% after cancer therapy. Whole-exome sequencing in 14 PPCM patients with cancer revealed that 43% (6 of 14 patients) carried likely pathogenic (Class IV) or pathogenic (Class V) gene variants associated with DCM/HCM in CPT2, DSP, MYH7, TTN, and/or with CPS in ATM, ERCC5, NBN, RECQL4, and SLX4. All CPS variants affected DNA damage response genes. Conclusions Cardiotoxic cancer therapy before PPCM is associated with delayed full recovery. The high cancer prevalence in PPCM is linked to likely pathogenic/pathogenic gene variants associated with DCM/HCM and/or CPS/DNA damage response–related cancer risk. This may warrant genetic testing and screening for heart failure in pregnant women with a cancer history and screening for cancer in PPCM patients