A Double-Blind, Randomized, Placebo-Controlled Study of Pancreatin 25000 Minimicrospheres for Pancreatic Exocrine Insufficiency After Major Pancreatic Resection

Context Pancreatic exocrine insufficiency (PEI) may occur following major pancreatic resection. Objective To demonstrate superior efficacy of pancreatin 25000 minimicrospheres over placebo in treating PEI after pancreatic resection. Patients and Methods A 1-week, double-blind (DB), randomized, placebo-controlled, parallel-group, multicenter study with 1-year open-label extension (OLE). Subjects ³18-year-old with PEI after pancreatic resection, defined as baseline coefficient of fat absorption (CFA) <80%, were randomized to oral pancreatin or placebo (9-15 capsules/day: 3 with main meals, 2 with snacks). In the OLE, all subjects received pancreatin. The primary efficacy measure was least squares (LS) mean CFA change from baseline to end of DB treatment (ANCOVA). Results All 58 subjects randomized (32 pancreatin, 26 placebo) completed the DB phase and entered the OLE; 51 completed the OLE. In the DB phase, the LS mean CFA change was significantly greater with pancreatin vs. placebo: 21.4% (95% CI: 13.7-29.2%) vs. -4.2% (95% CI: -12.8-4.5%); difference 25.6% (95% CI: 13.9-37.3%), P<0.001. In subjects randomized to pancreatin, the mean±SD CFA increase at the end of the OLE was 20.3±24.7%. Treatment-emergent adverse events (TEAEs) occurred in 37.5% subjects on pancreatin and 26.9% on placebo during DB treatment and in 75.9% during the OLE. The most common TEAEs were gastrointestinal disorders (DB: pancreatin 21.9%, placebo 11.5%; OLE: 6.9% patients). Conclusion This study demonstrates superior efficacy of pancreatin 25000 over placebo in patients with PEI after major pancreatic resection, as measured by change in CFA, with an expected safety and tolerability profile at the dosage administered. Supported by Abbott. Hannover, Germany

Unfolding the Secrets of Small Cell Lung Cancer Progression: Novel Approaches and Insights Through Rapid Autopsies

The understanding of small cell lung cancer (SCLC) biology has increased dramatically in recent years, but the processes that allow SCLC to progress rapidly remain poorly understood. Here, we advocate the integration of rapid autopsies and preclinical models into SCLC research as a comprehensive strategy with the potential to revolutionize current treatment paradigms

New genetic loci link adipose and insulin biology to body fat distribution.

Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 × 10(-8)). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms

Minimal information for studies of extracellular vesicles (MISEV2023): From basic to advanced approaches

Extracellular vesicles (EVs), through their complex cargo, can reflect the state of their cell of origin and change the functions and phenotypes of other cells. These features indicate strong biomarker and therapeutic potential and have generated broad interest, as evidenced by the steady year-on-year increase in the numbers of scientific publications about EVs. Important advances have been made in EV metrology and in understanding and applying EV biology. However, hurdles remain to realising the potential of EVs in domains ranging from basic biology to clinical applications due to challenges in EV nomenclature, separation from non-vesicular extracellular particles, characterisation and functional studies. To address the challenges and opportunities in this rapidly evolving field, the International Society for Extracellular Vesicles (ISEV) updates its 'Minimal Information for Studies of Extracellular Vesicles', which was first published in 2014 and then in 2018 as MISEV2014 and MISEV2018, respectively. The goal of the current document, MISEV2023, is to provide researchers with an updated snapshot of available approaches and their advantages and limitations for production, separation and characterisation of EVs from multiple sources, including cell culture, body fluids and solid tissues. In addition to presenting the latest state of the art in basic principles of EV research, this document also covers advanced techniques and approaches that are currently expanding the boundaries of the field. MISEV2023 also includes new sections on EV release and uptake and a brief discussion of in vivo approaches to study EVs. Compiling feedback from ISEV expert task forces and more than 1000 researchers, this document conveys the current state of EV research to facilitate robust scientific discoveries and move the field forward even more rapidly

Genome sequencing and analysis of the versatile cell factory Aspergillus niger CBS 513.88

The filamentous fungus Aspergillus niger is widely exploited by the fermentation industry for the production of enzymes and organic acids, particularly citric acid. We sequenced the 33.9-megabase genome of A. niger CBS 513.88, the ancestor of currently used enzyme production strains. A high level of synteny was observed with other aspergilli sequenced. Strong function predictions were made for 6,506 of the 14,165 open reading frames identified. A detailed description of the components of the protein secretion pathway was made and striking differences in the hydrolytic enzyme spectra of aspergilli were observed. A reconstructed metabolic network comprising 1,069 unique reactions illustrates the versatile metabolism of A. niger. Noteworthy is the large number of major facilitator superfamily transporters and fungal zinc binuclear cluster transcription factors, and the presence of putative gene clusters for fumonisin and ochratoxin A synthesis

Cell Cycle Analysis of Cultured Mammalian Cells after Exposure to 4,5′,8-Trimethylpsoralen and Long-Wave Ultraviolet Light

Cell cycle analysis was used to study the effect of 4,5′,8-trimethylpsoralen (TMP) and long-wave ultraviolet light (UV-A) on cultured mammalian cells. DNA distribution patterns were measured for murine melanoma cells (a cloned line of Cloudman S91) and a strain of diploid human skin fibroblasts (CRL 1295) using both a micro-fluorimetry procedure and flow cytometry. The untreated cells and those receiving TMP alone and UV-A alone had identical DNA content as assessed at several posttreatment intervals (0–72 hr). The majority of cells in control groups contained a G1 DNA content, whereas exposure to TMP (2 × 10−7 m) plus UV-A (1 Joule/cm2) led to the accumulation of cells in the G2 phase. These observations were similar for each cell type and both analytical techniques were in excellent agreement. The finding that psoralen plus UV-A induces a phase-specific G2 blockade in cultured cells has important implications for understanding the mechanisms which account for enhanced pigmentation and suppression of cellular proliferation following exposure to these agents in vivo