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Dietary restriction (DR) promotes healthy aging in diverse species. Essential amino acids play a key role, but the molecular mechanisms are unknown. The evolutionarily conserved Sestrin protein, an inhibitor of activity of the target of rapamycin complex 1 (TORC1), has recently been discovered as a sensor of amino acids in vitro. Here, we show that Sestrin null mutant flies have a blunted response of lifespan to DR. A mutant Sestrin fly line, with blocked amino acid binding and TORC1 activation, showed delayed development, reduced fecundity, extended lifespan and protection against lifespan-shortening, high-protein diets. Sestrin mediated reduced intestinal stem cell activity and gut cell turnover from DR, and stem cell proliferation in response to dietary amino acids, by regulating the TOR pathway and autophagy. Sestrin expression in intestinal stem cells was sufficient to maintain gut homeostasis and extend lifespan. Sestrin is thus a molecular link between dietary amino acids, stem cell function and longevity. The authors identify the evolutionarily conserved amino acid-sensing protein Sestrin as a key mediator of dietary restriction benefits in flies. Sestrin regulates gut stem cell activity via the TOR pathway, resulting in improved gut health and longevity.

The aims of this study were to analyse the occurrence of aflatoxins, aflatoxin M1 (AFM1), fumonisins, ochratoxin A (OTA), patulin (PAT), zearalenone (ZEN) and deoxynivalenol (DON) in foodstuffs consumed in Chile between 2008 and 2017 and to estimate the contribution of main contaminated foodstuff in human exposure by the probable daily intake (PDI) estimation. In 9 years of surveillance, 2020 food samples were analysed with an occurrence of 18.2% and with 2.7% of the samples being over the Chilean regulation. The occurrence of mycotoxins in food were 16% for aflatoxins, 6% for AFM1, 30% for OTA, 12% for DON, 7% for PAT, 21% for fumonisins and 2% for ZEN. The estimated median PDI of DON because of bread consumption was 129.2 ng/kg bw/day for children and 96.0 ng/kg bw/day in adults. Median PDI because of capsicum consumption was 0.006 ng/kg bw/day for OTA and 0.005 ng/kg bw/day for aflatoxins. Median PDI of aflatoxins was estimated at 0.02 ng/kg bw/day for spices and 0.04 ng/kg bw/day for nuts consumption. In children, the median PDI of AFM1 for dairy consumption was 0.07 ng/kg bw/day. The derived margin of exposure (MoE) values ranged from 1133 to 8500 suggested that aflatoxins would be of public health concern. The PDI of the other mycotoxins did not show a health risk. This is the first survey of mycotoxins in food made in Chile; further research is needed to improve surveillance and guidelines based on national risk assessments and considering sensitive population groups.

As treatment results for high-risk soft tissue sarcoma are still disappointing, treatment intensification is warranted. We performed a retrospective analysis of multimodal preoperative treatment to evaluate the additional effect of concurrent chemotherapy and/or locoregional hyperthermia in comparison to radiotherapy alone. Between 1999 and 2011, 28 patients were treated with neoadjuvant radiotherapy to a median 45 Gy for high-risk soft tissue sarcoma. All tumors were deep-seated and grade 2 or 3, 86% (n = 24) larger than 5 cm. Multimodal treatment (n = 12) consisted of ifosfamide (n = 7), locoregional hyperthermia (n = 3), or both modalities (n = 2) concurrent to radiotherapy. Prognostic factors (grade, size, histology, location) were balanced in the groups with and without concurrent multimodal treatment. There was a significant improvement of disease-specific survival (100% vs. 70% at 3 years, p = 0.03) with multimodal treatment. Distant metastases-free survival was influenced, but was not statistically significant. Local control and disease-free survival did not differ in the two groups. Our data suggest that multimodal treatment with ifosfamide and/or locoregional hyperthermia in combination with neoadjuvant radiotherapy might improve outcome in high-risk soft tissue sarcomas.

Eine 52-jahrige Patientin wurde wegen progredienter Thrombosen unter therapeutischer Antikoagulation sowie Leukozytose mit Eosinophilie und Thrombozytopenie stationar aufgenommen. Bei Aufnahme prasentierte sich die Patientin mit Dyspnoe und Schwellung des linken Beins und Arms. Im Labor fielen eine Leukozytose (31 000/μl) mit Eosinophilie (54%), eine Thrombozytopenie (58 000/μl) und ein erhohtes C-reaktives Protein von 247 mg/dl (Normwert < 5 mg/dl) auf. In der Bildgebung waren eine Lungenembolie beidseits sowie ein leicht vergroserter Leistenlymphknoten nachweisbar. Die Biopsie des Lymphknotens (LK) ergab histologisch eine teils epitheloide, teils spindelige tumorose Lasion mit leicht vermehrter Gewebseosinophilie, passend zu einem inflammatorischen myofibroblastaren Tumor (IMT). Nach Resektion des LK links inguinal kam es zu einer sofortigen Ruckbildung der paraneoplastischen Eosinophilie und Thrombozytopenie. Anschliesend wurde eine antiinflammatorische Therapie mit Ibuprofen eingeleitet. 3 Monate nach Entlassung war bildgebend kein Rezidiv sowie klinisch kein Anhalt fur ein erneutes paraneoplastisches Syndrom nachweisbar. Der IMT ist ein seltener Weichgewebstumor von intermediarer Dignitat mit geringer Metastasierungsneigung. Er wird immer wieder von paraneoplastischen Syndromen begleitet. Die Therapie der Wahl besteht in der kompletten Tumorentfernung, bei nicht resektablen Tumoren wurden Kortikosteroide oder nichtsteroidale Antirheumatika erfolgreich eingesetzt. Aufgrund des sehr variablen klinischen Verlaufs von spontaner Ruckbildung bis hin zu Metastasierung konnte es sich beim IMT um verschiedene Entitaten (inflammatorisch, neoplastisch, autoimmun) handeln, die histologisch noch nicht ausreichend voneinander abgegrenzt werden konnen. Wichtig ist daher eine klinische Abschatzung der Dignitat so lange, bis eine Subtypisierung dieser seltenen Erkrankung moglich ist

Routine prophylactic antiemetic treatment of surgical patients appears justified only in case of an increased risk of postoperative nausea and vomiting (PONV.). The objective of this investigation was to assess the feasibility and efficacy of a dichotomized risk score adapted management of PONV. based on ondansetron prophylaxis and treatment with respect to the overall institutional rate of PONV. After estimating the individual PONV. risk by a simplified score, 162 adult patients scheduled for elective surgery received either 4 mg ondansetron intravenously (two to four risk factors = high-risk) or no prophylaxis (zero to one risk factor = low-risk). For antiemetic treatment ondansetron was given intravenously and orally. Incidence of PONV. was recorded during the first 24 hr after recovery. Data from 159 subjects were analyzed with 44 patients classified as low-risk and 115 patients classified as high-risk. Nine low-risk and 58 high-risk patients experienced PONV. The expected institutional PONV. incidence of 47% was reduced to 36%. Treatment with ondansetron was necessary in seven low-risk and 37 high-risk patients with a complete response rate of 71% (lowrisk) and 43% (high-risk). Providing antiemetic prophylaxis with ondansetron to high-risk patients strictly based on a simplified risk score can reduce the overall institutional rate of PONV. However, classifying patients into two groups while using ondansetron as the single antiemetic in the high-risk group appears to be of limited efficacy as the incidence of PONV in high-risk patients is still double that of low-risk patients.

Zum nahen Beginn der Pollensaison berichten internationale Referenten des 5. Europaischen Pollenflugsymposiums der Stiftung Deutscher Polleninformationsdienst, das am 8. September 2000 in Wien statt fand, uber die Bedeutung der Pollen-Grenzwertbestimmung.