in English, German Zusammenfassung. Der vorliegende systematische Überblicksartikel basiert auf Vorarbeiten im Rahmen der Erstellung der AWMF-S3-Leitlinien zur Therapie von Autismus-Spektrum-Störungen (ASS). Das Ziel ist, den aktuellen Stand evidenzbasierter Interventionen zur Behandlung der Kernsymptomatik sowie sprachlichen Förderung im Kleinkind- und Vorschulalter für Kinder mit ASS darzustellen. Einschlusskriterien entwicklungsorientierte oder verhaltenstherapeutisch basierte, manualisierte Intervention für Kinder mit ASS nach DSM-III (R), DSM-IV (TR), DSM-5 oder ICD-10, Alter kontrollierte klinische Studie. Zielgrößen der eingeschlossenen Studien zentrale autismusspezifische Symptomatik oder entwicklungspsychologisch belegte Vorläuferfertigkeiten oder Verbesserung der sprachlichen Fertigkeiten. Die Interventionen wurden (1) anhand ihrer wöchentlichen Frequenz sowie (2) anhand der therapeutischen Inhalte sortiert. Spezifische Therapieinhalte, wie die Förderung elterlicher Synchronizität sowie kindlicher gemeinsamer Aufmerksamkeit, Symbolspiel und Imitation einerseits oder die umfassende Förderung verschiedener Entwicklungsbereiche andererseits, wurden in den entsprechenden Studien untersucht. Die soziale Interaktion und Kommunikation verbesserte sich langfristig durch das frühe Training elterlicher Synchronizität und kindlicher Reziprozität sowie durch niedrigfrequente, umfassende, entwicklungsorientierte Therapieprogramme, denen das natürliche Lernformat zugrunde liegt.  https://www.selleckchem.com/products/GDC-0980-RG7422.html  Hochfrequente, am diskreten Lernformat orientierte Programme zeigten diesbezüglich keine Effekte. Sprachliche Fertigkeiten verbesserten sich ebenfalls durch umfassende Förderung. Der Artikel summiert abschließend die Empfehlungen zu der in diesem Artikel untersuchten Fragestellung.Hereditary transthyretin-mediated amyloidosis is an inherited, rapidly progressive, life-threatening disease caused by mutated transthyretin (TTR) protein. Patisiran is a small interfering RNA (siRNA) formulated in a lipid nanoparticle that inhibits hepatic TTR protein synthesis by RNA interference. We have developed an indirect-response pharmacokinetic-pharmacodynamic model relating plasma siRNA (ALN-18328) levels to serum TTR reduction across five clinical studies. A sigmoidal function described this relationship, with estimated Hill coefficient of 0.548, and half maximal inhibitory concentration (IC50), IC80, and IC90 values of 9.45, 118.5, and 520.5 ng/mL, respectively. Following patisiran 0.3 mg/kg every 3 weeks (q3w), steady-state plasma ALN-18328 exposures were between IC80 and IC90, yielding average serum TTR reductions of 80%-90% from baseline. Covariate analysis indicated similar TTR reduction across evaluated intrinsic and extrinsic factors, obviating the need for dose adjustment. Modeling results support the recommended patisiran dosing schedule of 0.3 mg/kg q3w, with a maximum dose of 30 mg for patients weighing ≥100 kg.Purpose To present the outcomes of the laparoscopic and robotic treatment of pediatric simple renal cysts with two novel modifications the indocyanine green (ICG) fluorescence and the perirenal fat tissue wadding technique. Methods Between 2012 and 2019, 13 patients with solitary renal cysts were treated through minimally invasive approach. Preoperative work-up included ultrasonography and computed tomography or magnetic resonance. A cyst deroofing was performed in all cases. In the last 3 cases, the ICG fluorescence technique enabled a clear identification and safe puncture of the cyst dome. Five cysts were filled with perirenal fat tissue after deroofing. Results Thirteen patients (9 boys) were treated through laparoscopic (6 patients), retroperitoneoscopic (3 patients), or robotic approach (4 patients). Median age was 8 years (5-15 years). The median cyst size was 70 mm (42-160 mm). Eight cysts were located in the right kidney. All cysts were progressive and symptomatic. Thirteen cysts (100%) were graded as type II according to the Bosniak classification. No conversion was recorded. The median operative time for laparoscopy was 50 minutes (35-90 minutes) and 85 minutes for robotics (65-120 minutes) including surgical and docking time. No intraoperative complications occurred. The median hospital stay was 2 days (36-96 hours). No residual liquid was detected on follow-up after deroofing and fat tissue wadding technique. Conclusions Cyst deroofing is an effective and durable treatment for symptomatic simple renal cysts. Robotics enables excellent tissue dissection and ergonomics. The perirenal fat tissue wadding of the cyst seems to reduce the recurrence rate. The ICG fluorescence technique allows for better identification of the cyst and safer surgical procedure.Rhizomucor miehei lipase (RML) is a biocatalyst that widely used in laboratory and industrial. Previously, RML with a 70-amino acid propeptide (pRML) was cloned and expressed in P. pastoris. Recombinant strains with (strain containing 4-copy prml) and without ER stress (strain containing 2-copy prml) were obtained. However, the effective expression of pRML in P. pastoris by coexpressing ER-related elements in pRML-produced strain with or without ER stress has not been reported to date. In this study, an efficient way to produce functional pRML was explored in P. pastoris. The coexpression of protein folding chaperones, including PDI and ERO1, in different strains with or without ER stress, was investigated. PDI overexpression only increased pRML production in 4-copy strain from 705 U/mL to 1430 U/mL because it alleviated the protein folded stress, increased the protein concentration from 0.56  mg/mL to 0.65 mg/mL, and improved enzyme-specific activity from 1238 U/mg to 2186 U/mg. However, PDI coexpression could not improve pRML production in the 2-copy strain because it increased protein folded stress, while ERO1 coexpression in the two strains all had a negative effect on pRML expression. We also investigated the effect of the propeptide on the substrate specificity and the condition for pRML enzyme powder preparation. Results showed that the relative activity exceeded 80% when the substrates C8-C10 were detected at 35°C and pH 6, and C8-C12 at 45°C and pH 8. The optimal enzyme powder preparation pH was 7, and the maximum recovery rate for pRML was 73.19%.