Das RLS in der älteren Bevölkerung - Auswertung der Daten der TREND-Studie in Bezug auf RLS und dessen Zusammenhang zu TCS-Befunden und Prodromalmarkern für Morbus Parkinson

Das Restless Legs Syndrom (RLS) gilt als eine der häufigsten neurologischen Erkrankungen der westlichen Bevölkerung und betrifft insbesondere auch ältere Menschen. Eine Assoziation von RLS mit der Depression gilt als gesichert. Es ist weiterhin bekannt, dass das RLS bei Morbus Parkinson gehäuft auftritt. Jedoch ist bisher unklar, ob das RLS in Kombination mit anderen Prodromalmarkern als Frühzeichen für Morbus Parkinson gewertet werden kann. Die vorliegende Studie erhob in einem Kollektiv älterer Personen (Alter im Mittel 64,5 Jahre), die bezüglich des Vorliegens von Prodromalmarkern für Parkinson (und Alzheimer) rekrutiert und stratifiziert waren, die Prävalenz für das RLS sowie dessen Assoziation zur Depression. Als Prodromalmarker für Morbus Parkinson wurden eine Depression/depressive Verstimmung, eine Hyposmie sowie eine Rapid-Eye-Movement-Sleep-Behaviour-Disorder (RBD) untersucht. Ziel war daneben, ein Bild-morphologisches Korrelat für das RLS und die Depression im Rahmen der transkraniellen Sonographie (TCS) zu erheben. Die untersuchten Probanden (n = 1102) wurden aus dem ersten Follow-Up der TREND-Studie (Tübinger Erhebung von Risikofaktoren zur Erkennung von Neurodegeneration) rekrutiert. Die Analyse umfasste das Vorliegen eines RLS, einer vorhandenen lifetime depression, sowie Auffälligkeiten in der TCS und möglicher Prodromalmarker für Morbus Parkinson. Die Prävalenz des RLS in der Literatur konnte im untersuchten Studienkollektiv bestätigt werden. Ebenso konnte ein bereits bekannter Zusammenhang zwischen Geschlecht und Erkrankungswahrscheinlichkeit (Frauen sind häufiger von RLS betroffen) auch in der hier untersuchten Kohorte belegt werden. Eine bestehende Assoziation von Depression und RLS wurde auch in unserem Kollektiv erhoben. Die für das RLS typische Auffälligkeit einer Hypoechogenität der Substantia nigra (SN) in der TCS sowie ein Bild-morphologisches Korrelat für die gleichzeitig bestehende Depression (unterbrochene Raphestruktur) konnten in unserer Studie nicht gefunden werden. Auf Grund einer erhöhten Anzahl an Probanden mit Risikomarkern für neurodegenerative Erkrankungen in der TREND-Kohorte ist es möglich, dass die Hypoechogenität der SN von der stärker sichtbaren Hyperechogenität der Substantia nigra (SN plus) in der TCS (als Zeichen eines möglichen Prodromalstadiums) überlagert wird. Es fand sich jedoch eine Assoziation von RBD und RLS sowie ein gehäuftes Zusammentreffen von Prodromalmarkern für die Parkinson-Erkrankung und dem RLS, die das RLS als möglichen Prodromalmarker für Morbus Parkinson erscheinen lassen. Hierzu finden sich in der aktuellen Literatur widersprüchliche Aussagen. Weitere Untersuchungen werden notwendig sein, um das RLS als möglichen Prodromalmarker für Morbus Parkinson zu definieren oder auszuschließen und eine potentielle Assoziation von RBD und RLS zu untermauern oder zu verwerfen

Quantitative and qualitative estimation of atherosclerotic plaque burden in vivo at 7T MRI using Gadospin F in comparison to en face preparation evaluated in ApoE KO

Background The aim of the study was to quantify atherosclerotic plaque burden by volumetric assessment and T1 relaxivity measurement at 7T MRI using Gadospin F (GDF) in comparison to en face based measurements. Methods and results 9-weeks old ApoE-/- (n = 5 for each group) and wildtype mice (n = 5) were set on high fat diet (HFD). Progression group received MRI at 9, 13, 17 and 21 weeks after HFD initiation. Regression group was reswitched to chow diet (CD) after 13 weeks HFD and monitored with MRI for 12 weeks. MRI was performed before and two hours after iv injection of GDF (100 μmol/kg) at 7T (Clinscan, Bruker) acquiring a 3D inversion recovery gradient echo sequence and T1 Mapping using Saturation Recovery sequences. Subsequently, aortas were prepared for en face analysis using confocal microscopy. Total plaque volume (TPV) and T1 relaxivity were estimated using ImageJ (V. 1.44p, NIH, USA). 2D and 3D en face analysis showed a strong and exponential increase of plaque burden over time, while plaque burden in regression group was less pronounced. Correspondent in vivo MRI measurements revealed a more linear increase of TPV and T1 relaxivity for regression group. A significant correlation was observed between 2D and 3D en face analysis (r = 0.79; p<0.001) as well as between 2D / 3D en face analysis and MRI (r = 0.79; p<0.001; r = 0.85; p<0.001) and delta R1 (r = 0.79; p<0.001; r = 0.69; p<0.01). Conclusion GDF-enhanced in vivo MRI is a powerful non-invasive imaging technique in mice allowing for reliable estimation of atherosclerotic plaque burden, monitoring of disease progression and regression in preclinical studies

Recommendations for the Use of Antibiotics in Primary and Secondary Esthetic Breast Surgery

The use of systemic prophylactic antibiotics to reduce surgical-site infection in esthetic breast surgery remains controversial, although the majority of surgeons prefer to utilize antibiotics to prevent infection. Nonetheless, postoperative acute and subclinical infection and capsular fibrosis are among the most common complications following implant-based breast reconstruction. After esthetic breast augmentation, up to 2.9% of women develop infection, with an incidence rate of 1.7% for acute infections and 0.8% for late infections. After postmastectomy reconstruction (secondary reconstruction), the rates are even higher. The microorganisms seen in acute infections are Gram-positive, whereas subclinical late infections involving microorganisms are typically Gram-negative and from normal skin flora with low virulence. In primary implantation, a weight-based dosing of cefazolin is adequate, an extra duration of antibiotic cover does not provide further reduction in superficial or periprosthetic infections. Clindamycin and vancomycin are recommended alternative for patients with β-lactam allergies. The spectrum of microorganism found in late infections varies (Gram-positive and Gram-negative), and the antibiotic prophylaxis (fluoroquinolones) should be extended by vancomycin and according to the antibiogram when replacing implants and in secondary breast reconstruction, to target microorganisms associated with capsular contracture. All preoperative antibiotics should be administered <60 minutes before incision to guarantee high serum levels during surgical procedure

Thyroid-Hormone-Induced Browning of White Adipose Tissue Does Not Contribute to Thermogenesis and Glucose Consumption.

Regulation of body temperature critically depends on thyroid hormone (TH). Recent studies revealed that TH induces browning of white adipose tissue, possibly contributing to the observed hyperthermia in hyperthyroid patients and potentially providing metabolic benefits. Here, we show that browning by TH requires TH-receptor β and occurs independently of the sympathetic nervous system. The beige fat, however, lacks sufficient adrenergic stimulation and is not metabolically activated despite high levels of uncoupling protein 1 (UCP1). Studies at different environmental temperatures reveal that TH instead causes hyperthermia by actions in skeletal muscle combined with a central body temperature set-point elevation. Consequently, the metabolic and thermogenic effects of systemic hyperthyroidism were maintained in UCP1 knockout mice, demonstrating that neither beige nor brown fat contributes to the TH-induced hyperthermia and elevated glucose consumption, and underlining that the mere presence of UCP1 is insufficient to draw conclusions on the therapeutic potential of browning agents

Overt Cleft Palate Phenotype and TBX1 Genotype Correlations in Velo-cardio-facial/DiGeorge/22q11.2 Deletion Syndrome Patients

Velo-cardio-facial syndrome/DiGeorge syndrome, also known as 22q11.2 deletion syndrome (22q11DS) is the most common microdeletion syndrome, with an estimated incidence of 1/2,000 – 1/4,000 live births. Approximately 9–11% of patients with this disorder have an overt cleft palate (CP), but the genetic factors responsible for CP in the 22q11DS subset are unknown. The TBX1 gene, a member of the T-box transcription factor gene family, lies within the 22q11.2 region that is hemizygous in patients with 22q11DS. Inactivation of one allele of Tbx1 in the mouse does not result in CP, but inactivation of both alleles does. Based on these data, we hypothesized that DNA variants in the remaining allele of TBX1 may confer risk to CP in patients with 22q11DS. To test the hypothesis, we evaluated TBX1 exon sequencing (n = 360) and genotyping data (n = 737) with respect to presence (n = 54) or absence (n = 683) of CP in patients with 22q11DS. Two upstream SNPs (rs4819835 and rs5748410) showed individual evidence for association but they were not significant after correction for multiple testing. Associations were not identified between DNA variants and haplotypes in 22q11DS patients with CP. Overall, this study indicates that common DNA variants in TBX1 may be nominally causative for CP in patients with 22q11DS. This raises the possibility that genes elsewhere on the remaining allele of 22q11.2 or in the genome could be relevant

Genotype and Cardiovascular Phenotype Correlations With TBX1 in 1,022 Velo-Cardio-Facial/Digeorge/22q11.2 Deletion Syndrome Patients

Haploinsufficiency of TBX1, encoding a T-box transcription factor, is largely responsible for the physical malformations in velo-cardio-facial /DiGeorge/22q11.2 deletion syndrome (22q11DS) patients. Cardiovascular malformations in these patients are highly variable, raising the question as to whether DNA variations in the TBX1 locus on the remaining allele of 22q11.2 could be responsible. To test this, a large sample size is needed. The TBX1 gene was sequenced in 360 consecutive 22q11DS patients. Rare and common variations were identified. We did not detect enrichment in rare SNP (single nucleotide polymorphism) number in those with or without a congenital heart defect. One exception was that there was increased number of very rare SNPs between those with normal heart anatomy compared to those with right-sided aortic arch or persistent truncus arteriosus, suggesting potentially protective roles in the SNPs for these phenotype-enrichment groups. Nine common SNPs (minor allele frequency, MAF \u3e 0.05) were chosen and used to genotype the entire cohort of 1,022 22q11DS subjects. We did not find a correlation between common SNPs or haplotypes and cardiovascular phenotype. This work demonstrates that common DNA variations in TBX1 do not explain variable cardiovascular expression in 22q11DS patients, implicating existence of modifiers in other genes on 22q11.2 or elsewhere in the genome

A collection of bacterial isolates from the pig intestine reveals functional and taxonomic diversity.

Our knowledge about the gut microbiota of pigs is still scarce, despite the importance of these animals for biomedical research and agriculture. Here, we present a collection of cultured bacteria from the pig gut, including 110 species across 40 families and nine phyla. We provide taxonomic descriptions for 22 novel species and 16 genera. Meta-analysis of 16S rRNA amplicon sequence data and metagenome-assembled genomes reveal prevalent and pig-specific species within Lactobacillus, Streptococcus, Clostridium, Desulfovibrio, Enterococcus, Fusobacterium, and several new genera described in this study. Potentially interesting functions discovered in these organisms include a fucosyltransferase encoded in the genome of the novel species Clostridium porci, and prevalent gene clusters for biosynthesis of sactipeptide-like peptides. Many strains deconjugate primary bile acids in in vitro assays, and a Clostridium scindens strain produces secondary bile acids via dehydroxylation. In addition, cells of the novel species Bullifex porci are coccoidal or spherical under the culture conditions tested, in contrast with the usual helical shape of other members of the family Spirochaetaceae. The strain collection, called 'Pig intestinal bacterial collection' (PiBAC), is publicly available at www.dsmz.de/pibac and opens new avenues for functional studies of the pig gut microbiota