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BackgroundOn March 16, 2020, the federal government of Austria declared a nationwide lockdown due to the COVID-19 pandemic. Since the lockdown, screening examinations and routine checkups have been restricted to prevent the spread of the virus and to increase the hospitals’ bed capacity across the country. This resulted in a severe decline of patient referrals to the hospitals.ObjectiveTo assess the impact of the COVID-19 pandemic on the rate of newly diagnosed gynecological and breast cancers in Austria.MethodsData of 2077 patients from 18 centers in Austria with newly diagnosed gynecological or breast cancer between January and May 2019 and January and May 2020 were collected. Clinical parameters, including symptoms, performance status, co-morbidities, and referral status, were compared between the time before and after the COVID-19 outbreak.ResultsOur results showed a slight increase of newly diagnosed cancers in January and February 2020 as compared with 2019 (+2 and +35%, respectively) and a strong decline in newly diagnosed tumors since the lockdown: −24% in March 2020 versus March 2019, −49% in April 2020 versus April 2019, −49% in May 2020 versus May 2019. Two-thirds of patients diagnosed during the pandemic presented with tumor-specific symptoms compared with less than 50% before the pandemic (pConclusionsThe lockdown led to a decreased number of newly diagnosed gynecological and breast cancers. The decreased accessibility of the medical services and postponed diagnosis of potentially curable cancers during the COVID-19 pandemic may be a step backwards in our healthcare system and might impair cancer treatment outcomes. Therefore, new strategies to manage early cancer detection are needed to optimize cancer care in a time of pandemic in the future.

N-acetylaspartate (NAA) is synthesized by aspartate N-acetyltransferase (gene: Nat8l) from acetyl–coenzyme A and aspartate. In the brain, NAA is considered an important energy metabolite for lipid synthesis. However, the role of NAA in peripheral tissues remained elusive. Therefore, we characterized the metabolic phenotype of knockout (ko) and adipose tissue–specific (ako) Nat8l-ko mice as well as NAA-supplemented mice on various diets. We identified an important role of NAA availability in the brain during adolescence, as 75% of Nat8l-ko mice died on fat-free diet (FFD) after weaning but could be rescued by NAA supplementation. In adult life, NAA deficiency promotes a beneficial metabolic phenotype, as Nat8l-ko and Nat8l-ako mice showed reduced body weight, increased energy expenditure, and improved glucose tolerance on chow, high-fat, and FFDs. Furthermore, Nat8l-deficient adipocytes exhibited increased mitochondrial respiration, ATP synthesis, and an induction of browning. Conversely, NAA-treated wild-type mice showed reduced adipocyte respiration and lipolysis and increased de novo lipogenesis, culminating in reduced energy expenditure, glucose tolerance, and insulin sensitivity. Mechanistically, our data point to a possible role of NAA as modulator of pancreatic insulin secretion and suggest NAA as a critical energy metabolite for adipocyte and whole-body energy homeostasis.—Hofer, D. C., Zirkovits, G., Pelzmann, H. J., Huber, K., Pessentheiner, A. R., Xia, W., Uno, K., Miyazaki, T., Kon, K., Tsuneki, H., Pendl, T., Al Zoughbi, W., Madreiter-Sokolowski, C. T., Trausinger, G., Abdellatif, M., Schoiswohl, G., Schreiber, R., Eisenberg, T., Magnes, C., Sedej, S., Eckhardt, M., Sasahara, M., Sasaoka, T., Nitta, A., Hoefler, G., Graier, W. F., Kratky, D., Auwerx, J., Bogner-Strauss, J. G. N-acetylaspartate availability is essential for juvenile survival on fat-free diet and determines metabolic health.

Summary Quantitative subcellular metabolomic measurements can explain the roles of metabolites in cellular processes but are subject to multiple confounding factors. We developed stable isotope labeling of essential nutrients in cell culture-subcellular fractionation (SILEC-SF), which uses isotope-labeled internal standard controls that are present throughout fractionation and processing to quantify acyl-coenzyme A (acyl-CoA) thioesters in subcellular compartments by liquid chromatography-mass spectrometry. We tested SILEC-SF in a range of sample types and examined the compartmentalized responses to oxygen tension, cellular differentiation, and nutrient availability. Application of SILEC-SF to the challenging analysis of the nuclear compartment revealed a nuclear acyl-CoA profile distinct from that of the cytosol, with notable nuclear enrichment of propionyl-CoA. Using isotope tracing, we identified the branched chain amino acid isoleucine as a major metabolic source of nuclear propionyl-CoA and histone propionylation, thus revealing a new mechanism of crosstalk between metabolism and the epigenome.

NAT8L (N-acetyltransferase 8-like) catalyzes the formation of N-acetylaspartate (NAA) from acetyl-CoA and aspartate. In the brain, NAA delivers the acetate moiety for synthesis of acetyl-CoA that is further used for fatty acid generation. However, its function in other tissues remained elusive. Here, we show for the first time that Nat8l is highly expressed in adipose tissues and murine and human adipogenic cell lines and is localized in the mitochondria of brown adipocytes. Stable overexpression of Nat8l in immortalized brown adipogenic cells strongly increases glucose incorporation into neutral lipids, accompanied by increased lipolysis, indicating an accelerated lipid turnover. Additionally, mitochondrial mass and number as well as oxygen consumption are elevated upon Nat8l overexpression. Concordantly, expression levels of brown marker genes, such as Prdm16, Cidea, Pgc1α, Pparα, and particularly UCP1, are markedly elevated in these cells. Treatment with a PPARα antagonist indicates that the increase in UCP1 expression and oxygen consumption is PPARα-dependent. Nat8l knockdown in brown adipocytes has no impact on cellular triglyceride content, lipogenesis, or oxygen consumption, but lipolysis and brown marker gene expression are increased; the latter is also observed in BAT of Nat8l-KO mice. Interestingly, the expression of ATP-citrate lyase is increased in Nat8l-silenced adipocytes and BAT of Nat8l-KO mice, indicating a compensatory mechanism to sustain the acetyl-CoA pool once Nat8l levels are reduced. Taken together, our data show that Nat8l impacts on the brown adipogenic phenotype and suggests the existence of the NAT8L-driven NAA metabolism as a novel pathway to provide cytosolic acetyl-CoA for lipid synthesis in adipocytes.

Objective Correlation of descriptive psychosomatic factors and birth parameters for pregnancy-induced hypertension (PIH). Study design For this prospective study 508 pregnant (singleton) women from 16th-22nd gestational week (GW) were investigated by means of a semi-standardized questionnaire. Complete data concerning delivery were obtained from medical records. In addition to medical and sociodemographic risk factors, so far neglected parameters such as biographical information, personality factors, social environment, stress coping strategies and pregnancy-related anxieties were examined. A factor analysis was performed using a principal component method with subsequent varimax rotation. Main outcome measures Main outcome measures were imminent preterm delivery, PIH, factual preterm delivery before 37GW and birth weight Results Four hundred and eighty-eight qualified for evaluation and got included in the univariate logistic regression – 12.6% of them had PIH. The development of PIH showed a significant correlation with age (OR, 95% CI). Very young and older women were more likely to develop PIH. Development of PIH is significantly more frequent in women, whose parents adhered to an authoritarian educational style, had no emotional support of female friends, and a higher BMI. Women who always had been non-smokers and women who did not give up smoking during pregnancy, but only reduced the amount of cigarettes had the least probability of developing PIH, whereas total abandoning of smoking before and especially during pregnancy was associated with a significantly increased risk for the development of PIH. Conclusions This study suggests psychosomatic factors, BMI and smoking behavior to be relevant for the development of PIH.

Triacylglycerols are stored in eukaryotic cells within lipid droplets (LD). The LD core is enwrapped by a phospholipid monolayer with phosphatidylcholine (PC), the major phospholipid, and phosphatidylethanolamine (PE), a minor component. We demonstrate that the onset of LD formation is characterized by a change in cellular PC, PE, and phosphatidylserine (PS). With induction of differentiation of 3T3-L1 fibroblasts into adipocytes, the cellular PC/PE ratio decreased concomitant with LD formation, with the most pronounced decline between confluency and day 5. The mRNA for PS synthase-1 (forms PS from PC) and PS decarboxylase (forms PE from PS) increased after day 5. Activity and protein of PE N-methyltransferase (PEMT), which produces PC by methylation of PE, are absent in 3T3-L1 fibroblasts but were induced at day 5. High fat challenge induced PEMT expression in mouse adipose tissue. PE, produced via PS decarboxylase, was the preferred substrate for methylation to PC. A PEMT-GFP fusion protein decorated the periphery of LD. PEMT knockdown in 3T3-L1 adipocytes correlated with increased basal triacylglycerol hydrolysis. Pemt(-/-) mice developed desensitization against adenosine-mediated inhibition of basal hydrolysis in adipose tissue, and adipocyte hypotrophy was observed in Pemt(-/-) animals on a high fat diet. Knock-out of PEMT in adipose tissue down-regulated PS synthase-1 mRNA, suggesting coordination between PE supply and converting pathways during LD biosynthesis. We conclude that two consecutive processes not previously related to LD biogenesis, (i) PE production via PS and (ii) PE conversion via PEMT, are implicated in LD formation and stability.

First trimester amniotic fluid is an ultrafiltrate of maternal plasma and constitutes the major component of gestational sac volume (GSV). We hypothesized that GSV, assessed by 3-dimensional (3-D) ultrasound volumetry, would reflect function of the early uteroplacental unit and therefore provide a basis for predicting pregnancy outcome. We tested this hypothesis in 38 pregnancies which had first trimester GSV measurements by two investigators thus allowing determination of interobserver variation. Gestational age (GA) was based on a careful history and conventional 2-dimensional ultrasound measurements. Serum forβ-hCG, estradiol (E2) and progesterone (P) was obtained at the time of ultrasound examinations. “Normal” outcome was defined as confirmation of a viable fetus. “Abnormal outcome” was defined as either a “blighted ovum” or embryonic demise. Statistical analysis was performed by Independent t-test and regression analysis. There were 31 “normal” and 7 “abnormal” pregnancies studied between 5 and 11 weeks gestation (mean±SD 8.3±1.3 weeks). GSV was significantly correlated to GA (r=0.74,P

From January 1980 until December 1991, all complying patients suffering from early uncomplicated postoperative intestinal obstruction were managed according to a stepwise treatment protocol including

A 28-year-old woman developed puerperal endomyometritis and tertian malaria simultaneously. She delivered her child by vacuum extraction during week 41 of pregnancy in September 1994. The peripartal period was uneventful. Nine days post partum the patient was readmitted to hospital with fever and pain in the area of the episiotomy. On day 13 post partum a hysterectomy was performed because of suspected abscess-forming endomyometritis. Two days after the hysterectomy the patient developed septic temperatures, which persisted for 10 days. Tertian malaria due to Plasmodium vivax was found to be the cause of fever. The patient had been in Indonesia without anti-malarial prophylaxis in 1991. Two years later she travelled to Ghana, having taken mefloquine as prophylaxis. Malaria was obviously caused by reactivated hypnozoites in the liver, although the patient had never had an episode of fever associated with malaria before. This case proves that tertian malaria may "recur" even without previous manifestation, years after a stay in a region endemic for malaria.

Es wird anhand von 91 stationar aufgenommenen Patienten mit Coxarthrosen die Schmerzsymptomatik untersucht: Die Funktionseinschrankung mittels der Untersuchung der Huftrotation wird mit dem rontgenologisch gefundenen Schweregrad der Arthrosen verglichen. Die ausgewahlten zugleich klinisch und rontgenologisch schweren Falle werden mit den ausgewahlten sowohl klinisch wie auch rontgenologisch als noch leicht befundenen Coxarthrosefallen in ihrer Symptomatik verglichen und die Unterschiede unterstrichen.

To demonstrate the technical feasibility and capability of superconducting ac cables a 35 m long ac single phase test cable for 110 kV and 10 kA is under construction at present. The rigid cryogenic envelope has already been assembled. Good experience was gained with the applied mounting technique which is described. Wires consisting of a high purity Al-core enclosed by a thin layer of Nb are used as cable conductors. They were fabricated in lengths of several thousand meters under large scale conditions and exhibited excellent electrical behaviour. After manufacturing some dummies with pure Al-wires, a 50 m long originally sized flexible cable core consisting of superconducting wires and wrapped HDPE tape insulation was fabricated on conventional cable machinery in our cable works. Dielectric measurements at 4.2 K and 2.5 bar on originally sized and large scale fabricated cable core pieces yielded breakdown voltages, partial discharge inception voltages and dissipation factors which are compatible with cable standards. Two one phase 110 kV - 10 kA cable terminations have been constructed and tested. They showed satisfying behaviour with respect to stress and current loads.

Background Fasting induces specific molecular and metabolic adaptions in most organisms. In biomedical research fasting is used in metabolic studies to synchronize nutritional states of study subjects. Because there is a lack of standardization for this procedure, we need a deeper understanding of the dynamics and the molecular mechanisms in fasting. Results We investigated the dynamic changes of liver gene expression and serum parameters of mice at several time points during a 48 hour fasting experiment and then focused on the global gene expression changes in epididymal white adipose tissue (WAT) as well as on pathways common to WAT, liver, and skeletal muscle. This approach produced several intriguing insights: (i) rather than a sequential activation of biochemical pathways in fasted liver, as current knowledge dictates, our data indicates a concerted parallel response; (ii) this first characterization of the transcriptome signature of WAT of fasted mice reveals a remarkable activation of components of the transcription apparatus; (iii) most importantly, our bioinformatic analyses indicate p53 as central node in the regulation of fasting in major metabolic tissues; and (iv) forced expression of Ddit4, a fasting-regulated p53 target gene, is sufficient to augment lipolysis in cultured adipocytes. Conclusions In summary, this combination of focused and global profiling approaches provides a comprehensive molecular characterization of the processes operating during fasting in mice and suggests a role for p53, and its downstream target Ddit4, as novel components in the transcriptional response to food deprivation.