Platelet GPIIb supports initial pulmonary retention but inhibits subsequent proliferation of melanoma cells during hematogenic metastasis

Platelets modulate the process of cancer metastasis. However, current knowledge on the direct interaction of platelets and tumor cells is mostly based on findings obtained in vitro. We addressed the role of the platelet fibrinogen receptor glycoprotein IIb (integrin alpha IIb) for experimental melanoma metastasis in vivo. Highly metastatic B16-D5 melanoma cells were injected intravenously into GPIIb-deficient (GPIIb(-/-)) or wildtype (WT) mice. Acute accumulation of tumor cells in the pulmonary vasculature was assessed in real-time by confocal videofluorescence microscopy. Arrest of tumor cells was dramatically reduced in GPIIb(-/-) mice as compared to WT. Importantly, we found that mainly multicellular aggregates accumulated in the pulmonary circulation of WT, instead B16-D5 aggregates were significantly smaller in GPIIb(-/-) mice. While pulmonary arrest of melanoma was clearly dependent on GPIIb in this early phase of metastasis, we also addressed tumor progression 10 days after injection. Inversely, and unexpectedly, we found that melanoma metastasis was now increased in GPIIb(-/-) mice. In contrast, GPIIb did not regulate local melanoma proliferation in a subcutaneous tumor model. Our data suggest that the platelet fibrinogen receptor has a differential role in the modulation of hematogenic melanoma metastasis. While platelets clearly support early steps in pulmonary metastasis via GPIIb-dependent formation of platelet-tumor-aggregates, at a later stage its absence is associated with an accelerated development of melanoma metastases

COP26 Key Outcomes

Did COP26 in Glasgow save or doom us? A new report by ecbi, COP26 Key Outcomes, assesses the Glasgow Climate Summit on the level of political ambition it achieved as well as what it delivered on finance, loss and damage, transparency, common time frames, Article 6, and adaptation. It explains and evaluates key formal COP and CMA decisions, as well as the pledges and promises by various coalitions on issues ranging from coal to cars, methane to forests. The report suggests that, while Glasgow failed to deliver enough political ambition and disappointed in several key areas, it arguably did enough to signal a shift away from business-as-usual. What’s more, COP26 finalised the Paris Rulebook, providing the tools needed to make more significant progress down the line. The report also looks at what was left unfinished in Glasgow and what needs to happen in 2022 to maximise our chances of moving the needle at COP27 and beyond. Authored by experts with many years’ experience following the UNFCCC negotiations, the report features quotes and insights from ecbi’s network of negotiators and delegates who attended COP26

COP24: key outcomes

24th Conference of Parties to the UNFCC

Predictors of the resumption of menses in adolescent anorexia nervosa

Background: The resumption of menses is an important indicator of recovery in anorexia nervosa (AN). Patients with early-onset AN are at particularly great risk of suffering from the long-term physical and psychological consequences of persistent gonadal dysfunction. However, the clinical variables that predict the recovery of menstrual function during weight gain in AN remain poorly understood. The aim of this study was to investigate the impact of several clinical parameters on the resumption of menses in first-onset adolescent AN in a large, well-characterized, homogenous sample that was followed-up for 12 months. Methods: A total of 172 female adolescent patients with first-onset AN according to DSM-IV criteria were recruited for inclusion in a randomized, multi-center, German clinical trial. Menstrual status and clinical variables (i.e., premorbid body mass index (BMI), age at onset, duration of illness, duration of hospital treatment, achievement of target weight at discharge, and BMI) were assessed at the time of admission to or discharge from hospital treatment and at a 12-month follow-up. Based on German reference data, we calculated the percentage of expected body weight (%EBW), BMI percentile, and BMI standard deviation score (BMI-SDS) for all time points to investigate the relationship between different weight measurements and resumption of menses. Results: Forty-seven percent of the patients spontaneously began menstruating during the follow-up period. %EBW at the 12-month follow-up was strongly correlated with the resumption of menses. The absence of menarche before admission, a higher premorbid BMI, discharge below target weight, and a longer duration of hospital treatment were the most relevant prognostic factors for continued amenorrhea. Conclusions: The recovery of menstrual function in adolescent patients with AN should be a major treatment goal to prevent severe long-term physical and psychological sequelae. Patients with premenarchal onset of AN are at particular risk for protracted amenorrhea despite weight rehabilitation. Reaching and maintaining a target weight between the 15th and 20th BMI percentile is favorable for the resumption of menses within 12 months. Whether patients with a higher premorbid BMI may benefit from a higher target weight needs to be investigated in further studies

Hybrid cutting of granite by use of ultrasonic assistance

Hybrid technologies offer an important approach to enhance existing limits of conventional cutting manufacturing processes. Superposition of the infeed with adapted ultrasonic vibrations enables reductions of machining forces. This results in diminished tool wear and longer tool life. Furthermore, an increase of removal rates can be achieved. Successful machining of recalcitrant metal-based materials by ultrasonic assisted systems creates a high potential to gain similar effects in machining of mineral-based materials. This will be studied in this article. The state of the art for the machining of stone uses geometrically undefined cutting edges. This paper focuses on the geometrically defined cutting of granite with additional ultrasonic assistance. Cutting tests at a test station with linear cutting motion are being performed. The ultrasonic frequency is maintained at 20 kHz. Different oscillation amplitudes are applied to influence process forces and the wear of the used carbide metal and polycrystalline diamond cutting segments (PCD). A method to observe the wear is developed by use of a stereomicroscope and a 3D measurement system. This will enable conclusions about the applicability of the geometry of the cutting segments and the process parameters. Due to the significant different wear rates of both cutting materials, the cutting force progression by using PCD tools shows completely different characteristics compared to the machining with carbide metal tools