Cyst Features and Risk of Malignancy in Intraductal Papillary Mucinous Neoplasms of the Pancreas: Imaging and Pathology

Background: Intraductal papillary mucinous neoplasms (IPMNs) display diverse macroscopic, histological, and immunohistochemical characteristics with typical morphological appearance in magnetic resonance imaging. Depending on those, IPMNs may show progression into invasive carcinomas with variable frequency. Overall, IPMN-associated invasive carcinomas are found in about 30% of all IPMNs, revealing phenotpyes comparable with conventional ductal adenocarcinomas or mucinous (colloid) carcinomas of the pancreas. In Sendai-negative side-branch IPMNs, however, the annual risk of the development of invasive cancer is 2%; thus, risk stratification with regard to imaging and preoperative biomarkers and cytology is mandatory. Methods and Results: The present study addresses the radiological and interventional preoperative measures including histological features to determine the risk of malignancy and the prognosis of IPMNs. Conclusion: While preoperative imaging largely relies on the detection of macroscopic features of IPMNs, which are associated with a divergent risk of malignant behavior, in resected specimens the determination of the grade of dysplasia and the detection of an invasive component are the most important features to estimate the prognosis of IPMNs

Neuromuscular, physiological and perceptual responses to an elite netball tournament

To examine responses to an International netball tournament, female athletes (n= 11) played three matches over consecutive days. External (accelerometry) and internal (heart rate; HR, session; sRPE, and differential; dRPE, rating of perceived exertion) load measures quantified match intensity. On match-day mornings, and three days after match 3, well-being (brief assessment of mood; BAM+), biochemical (creatine kinase concentration; CK), neuromuscular (jump height; JH, peak power output; PPO) and endocrine function (salivary cortisol; C, testosterone; T, concentrations) were assessed. External load was similar between matches whereas dRPE and sRPE were greatest for match 3. Following match 1, CK increased, whereas BAM+, JH, C and T decreased. Following two matches, BAM+, PPO, and T decreased with CK increasing versus baseline. Following consecutive matches, CK (likely moderate; 27.9% ± 19.5%) and C (possibly moderate; 43.3% ± 46.8%) increased, whilst BAM+ (possibly moderate; −20.6% ± 24.4%) decreased. Three days post-tournament BAM+, T, PPO, and JH decreased. Mid-court elicited higher mean HR (possibly moderate; 3.7% ± 3.8%), internal and external intensities (possibly very large; 85.7% ± 49.6%) compared with goal-based positions. Consecutive matches revealed a dose–response relationship for well-being and physiological function; a response evident three days post-tournament

The neuromuscular, physiological, endocrine and perceptual responses to different training session orders in international female netball players

The 20 h responses of International female netball players to training days requiring two sessions (netball and strength, separated by two hours) ordered alternatively were examined. Eleven players completed strength followed by netball training two hours later (STR-NET), with the order reversed (NET-STR) on a separate day. Well-being, neuromuscular performance (jump height [JH], peak power output [PPO], peak velocity [PV]) and endocrine function (testosterone, cortisol concentrations) were measured before sessions one (PreS1) and two (PreS2), immediately after sessions one (IPS1) and two (IPS2), and 20 h post session one (20P). Session and differential ratings of perceived exertion (upper-body, cognitive/technical [RPE-T], lower-body, breathlessness) were collected, and accelerometry and heart rate measured netball load. Identification of clear between-order differences was based on the nonoverlap of the 95% confidence interval (95%CI) for mean differences relative to baseline. Compared to PreS1, greater increases in JH (percentage difference between trials; 95%CI: 9%; 4–14%), PPO (5%; 2–8%), PV (3%; 1–5%) and cortisol concentration (45%; 1–88%), and a greater decrease for testosterone/cortisol ratio (−35%; −72 to −2%) occurred at PreS2 in NET-STR. At 20P, greater decreases in JH (10%; 5–15%), PPO (4%; 1–8%) and PV (4%; 2–6%) were observed following STR-NET. No differences existed for well-being, whilst RPE-T was greater (15 AU; 3–26 AU) for strength training during NET-STR. Session order influenced neuromuscular and endocrine responses in International female netball players, highlighting session ordering as a key consideration when planning training

Cyst Features and Risk of Malignancy in Intraductal Papillary Mucinous Neoplasms of the Pancreas: Imaging and Pathology

BACKGROUND: Intraductal papillary mucinous neoplasms (IPMNs) display diverse macroscopic, histological, and immunohistochemical characteristics with typical morphological appearance in magnetic resonance imaging. Depending on those, IPMNs may show progression into invasive carcinomas with variable frequency. Overall, IPMN-associated invasive carcinomas are found in about 30% of all IPMNs, revealing phenotpyes comparable with conventional ductal adenocarcinomas or mucinous (colloid) carcinomas of the pancreas. In Sendai-negative side-branch IPMNs, however, the annual risk of the development of invasive cancer is 2%; thus, risk stratification with regard to imaging and preoperative biomarkers and cytology is mandatory. METHODS AND RESULTS: The present study addresses the radiological and interventional preoperative measures including histological features to determine the risk of malignancy and the prognosis of IPMNs. CONCLUSION: While preoperative imaging largely relies on the detection of macroscopic features of IPMNs, which are associated with a divergent risk of malignant behavior, in resected specimens the determination of the grade of dysplasia and the detection of an invasive component are the most important features to estimate the prognosis of IPMNs

Acute physiological and perceptual responses to a netball specific training session in professional female netball players

The 24 h responses to professional female netball-specific training were examined. British Superleague players (n = 14) undertook a 90-min on-court training session incorporating key movement, technical, and scenario-specific match-play drills. Perceptual (mood, fatigue, soreness), neuromuscular (countermovement jump peak power output [PPO], PPO relative to mass [PPOrel], jump height [JH]), endocrine (salivary cortisol [C], testosterone [T] concentrations) and biochemical (creatine kinase concentrations [CK]) markers were assessed at baseline (immediately before; Pre), and immediately, two and 24 hours after (+0h, +2h, +24h) training. Session (sRPE) and differential (dRPE) ratings of perceived exertion were recorded at +0h. Identification of clear between time-point differences were based on the 95% confidence interval (CI) for mean differences relative to baseline values not overlapping. At +0h, C (raw unit mean difference from baseline; 95% CI: 0.16; 0.06 to 0.25 μg·dl(-1)), T (32; 20 to 45 pg⋅ml(–1)), CK (39; 28 to 50 u·L(-1)), PPOrel (2.4; 0.9 to 3.9 W·kg(-1)) and PPO (169; 52 to 286 W) increased. At +2h, fatigue (15; 7 to 24 AU), CK (49; 38 to 60 u·L(-1)), and soreness (14; 3 to 25 AU) increased, while T (-24; -37 to -11 pg⋅ml(–1)) and mood (-20; -27 to -12 AU) reduced. At +24h, CK increased (25; 13 to 36 u·L(-1)) whereas PPOrel (-1.6; -3.2 to -0.1 W·kg(-1)) and JH (-0.02; -0.03 to -0.08 m) reduced. Responses were variable specific, and recovery of all variables did not occur within 24h. The residual effects of the prior stimulus should be accounted for in the planning of training for professional female netball players

Endothelial dimethylarginine dimethylaminohydrolase 1 is an important regulator of angiogenesis but does not regulate vascular reactivity or hemodynamic homeostasis

Background—Asymmetrical dimethylarginine (ADMA) is an endogenous inhibitor of nitric oxide synthesis and a risk factor for cardiovascular disease. Dimethylarginine dimethylaminohydrolase (DDAH) enzymes are responsible for ADMA breakdown. It has been reported that endothelial DDAH1 accounts for the majority of ADMA metabolism. However, we and others have shown strong DDAH1 expression in a range of nonendothelial cell types, suggesting that the endothelium is not the only site of metabolism. We have developed a new endothelium-specific DDAH1 knockout mouse (DDAH1En−/−) to investigate the significance of endothelial ADMA in cardiovascular homeostasis. Methods and Results—DDAH1 deletion in the DDAH1En−/− mouse was mediated by Tie-2 driven Cre expression. DDAH1 deletion was confirmed through immunocytochemistry, whereas Western blotting showed that DDAH1 remained in the kidney and liver, confirming expression in nonendothelial cells. Plasma ADMA was unchanged in DDAH1En−/− mice, and cultured aortas released amounts of ADMA to similar to controls. Consistent with these observations, vasoreactivity ex vivo and hemodynamics in vivo were unaltered in DDAH1En−/− mice. In contrast, we observed significantly impaired angiogenic responses both ex vivo and in vivo. Conclusions—We demonstrate that endothelial DDAH1 is not a critical determinant of plasma ADMA, vascular reactivity, or hemodynamic homeostasis. DDAH1 is widely expressed in a range of vascular and nonvascular cell types; therefore, the additive effect of DDAH1 expression in multiple organ systems determines plasma ADMA concentrations. Endothelial deletion of DDAH1 profoundly impairs the angiogenic capacity of endothelial cells, indicating that intracellular ADMA is a critical determinant of endothelial cell response

The transcription factor Erg regulates expression of histone deacetylase 6 and multiple pathways involved in endothelial cell migration and angiogenesis

The endothelial ETS transcription factor Erg plays an important role in homeostasis and angiogenesis by regulating many endothelial functions including survival and junction stability. Here we show that Erg regulates endothelial cell (EC) migration. Transcriptome profiling of Erg-deficient ECs identified similar to 80 genes involved in cell migration as candidate Erg targets including many regulators of Rho-GTPases. Inhibition of Erg expression in HUVECs resulted in decreased migration in vitro, while Erg overexpression using adenovirus caused increased migration. Live-cell imaging of Erg-deficient HUVECs showed a reduction in lamellipodia, in line with decreased motility. Both actin and tubulin cytoskeletons were disrupted in Erg-deficient ECs, with a dramatic increase in tubulin acetylation. Among the most significant microarray hits was the cytosolic histone deacetylase 6 (HDAC6), a regulator of cell migration. Chromatin immunoprecipitation (ChIP) and transactivation studies demonstrated that Erg regulates HDAC6 expression. Rescue experiments confirmed that HDAC6 mediates the Erg-dependent regulation of tubulin acetylation and actin localization. In vivo, inhibition of Erg expression in angiogenic ECs resulted in decreased HDAC6 expression with increased tubulin acetylation. Thus, we have identified a novel function for the transcription factor Erg in regulating HDAC6 and multiple pathways essential for EC migration and angiogenesis. (Blood. 2012; 119(3):894-903

Global maps of twenty-first century forest carbon fluxes

Managing forests for climate change mitigation requires action by diverse stakeholders undertaking different activities with overlapping objectives and spatial impacts. To date, several forest carbon monitoring systems have been developed for different regions using various data, methods and assumptions, making it difficult to evaluate mitigation performance consistently across scales. Here, we integrate ground and Earth observation data to map annual forest-related greenhouse gas emissions and removals globally at a spatial resolution of 30 m over the years 2001–2019. We estimate that global forests were a net carbon sink of −7.6 ± 49 GtCO2e yr−1, reflecting a balance between gross carbon removals (−15.6 ± 49 GtCO2e yr−1) and gross emissions from deforestation and other disturbances (8.1 ± 2.5 GtCO2e yr−1). The geospatial monitoring framework introduced here supports climate policy development by promoting alignment and transparency in setting priorities and tracking collective progress towards forest-specific climate mitigation goals with both local detail and global consistency