ML 348

ML348 is a selective and reversible lysophospholipase 1 (LYPLA1) inhibitor (IC50 = 210 nM), Exhibits 14-fold selectivity for LYPLA1 over LYPLA2, Also selective over a panel of ~30 other serine hydrolases. target: LYPLA1 [1] IC 50： 210 nM [1]

References:
[1]. Adibekian A et al. Characterization of a Selective, Reversible Inhibitor of Lysophospholipase 1 (LYPLA1). National Center for Biotechnology Information (US); 2010- 2013 Apr 08.

Fiber-laser-based, high-repetition-rate, picosecond ultraviolet source tunable across 329-348 nm.[Pubmed:28005896]

Opt Lett. 2016 Oct 15;41(20):4799-4802.

We report a compact, fiber-laser-based, high-repetition-rate picosecond source for the ultraviolet (UV), providing multi-tens of milliwatt of average power across 329-348 nm. The source is based on internal sum-frequency-generation (SFG) in a singly resonant optical parametric oscillator (OPO), synchronously pumped at 532 nm by the second harmonic of a picosecond Yb-fiber laser at 80 MHz repetition rate. Using a 30-mm-long single-grating MgO:sPPLT crystal for the OPO and a 5-mm-long BiB₃O₆ crystal for intracavity SFG, we generate up to 115 mW of average UV power at 339.9 nm, with >50 mW over 73% of the tuning range, for 1.6 W of input pump power. The UV output exhibits a passive rms power stability of approximately 2.9% rms over 1 min and 6.5% rms over 2 h in high beam quality. Angular acceptance bandwidth and cavity detuning effects have also been studied.

Extent of undertreatment and overtreatment with cholesterol-lowering therapy according to European guidelines in 92,348 Danes without ischemic cardiovascular disease and diabetes in 2004-2014.[Pubmed:28038381]

Atherosclerosis. 2017 Feb;257:9-15.

BACKGROUND AND AIMS: We estimated the extent of undertreatment and overtreatment with cholesterol-lowering therapy according to European guidelines in individuals in the Danish general population without ischemic cardiovascular disease and diabetes. METHODS: We examined 92,348 such individuals aged 35-100 years recruited from 2004 through 2014 in the Copenhagen General Population Study. Each individual was assigned their 10-year risk of fatal cardiovascular disease according to the European SCORE chart based on age, sex, smoking, total cholesterol, and systolic blood pressure. European guidelines recommend cholesterol-lowering therapy definitely at >/=10% risk and LDL cholesterol >/=1.8 mmol/L, definitely at 5-9% risk and LDL cholesterol >/=2.5 mmol/L, possibly at 1-4% risk and LDL cholesterol >/=3 mmol/L, but not at <1% risk. RESULTS: 3858 individuals had >/=10% risk, 16,255 had 5-9% risk, 49,131 had 1-4% risk, and 23,104 had <1% 10-year risk of fatal cardiovascular disease. In these groups, 81%, 86%, 93%, and 99% did not receive cholesterol-lowering therapy. Definite undertreatment and overtreatment according to guidelines were found in 19% and 0.2% or in 187,660 and 1570 per million 35-100 year olds without ischemic cardiovascular disease and diabetes. If definite and possible undertreatment and overtreatment were combined, the corresponding numbers were 52% and 3% or 519,416 and 29,194 per million. CONCLUSIONS: In the Danish general population, approximately 190,000 per million 35-100 year olds without ischemic cardiovascular disease and diabetes are not treated to LDL cholesterol goals according to European guidelines. Conversely, approximately 1600 per million received cholesterol-lowering therapy without endorsement in European guidelines.

Pediatric spinal cord astrocytomas: a retrospective study of 348 patients from the SEER database.[Pubmed:28362182]

J Neurosurg Pediatr. 2017 Jun;19(6):711-719.

OBJECTIVE Intramedullary spinal cord tumors comprise 1%-10% of all childhood central nervous system neoplasms, with astrocytomas representing the most common subtype. Due to their rarity and poor prognosis, large population-based studies are needed to assess the epidemiology and survival risk factors associated with these tumors in the hope of improving outcome. The authors undertook this retrospective study to explore factors that may influence survival in pediatric patients with spinal cord astrocytomas. METHODS Utilizing the Surveillance, Epidemiology, and End Results (SEER) database, a prospective cancer registry, the authors retrospectively assessed survival in histologically confirmed, primary spinal cord astrocytomas in patients 21 years of age and younger. Survival was described with Kaplan-Meyer curves, and a multivariate regression analysis was used to assess the association of several variables with survival while controlling for confounding variables. RESULTS This analysis of 348 cases showed that age (hazard ratio [HR] 1.05, 95% CI 1.01-1.09, p = 0.017), nonwhite race (HR 1.74, 95% CI 1.11-2.74, p = 0.014), high-grade tumor status (HR 14.67, 95% CI 6.69-32.14, p < 0.001), distant or invasive extension of the tumor (HR 2.37, 95% CI 1.02-5.49, p = 0.046), and radiation therapy (HR 3.74, 95% CI 2.18-6.41, p < 0.001) were associated with decreased survival. Partial resection (HR 0.37, 95% CI 0.16-0.83, p = 0.017) and gross-total resection (HR 0.39, 95% CI 0.16-0.95, p = 0.039) were associated with improved survival. CONCLUSIONS Younger age appears to be protective, while high-grade tumors have a much worse prognosis. Early diagnosis and access to surgery appears necessary for improving outcomes, while radiation therapy has an unclear role. There is still much to learn about this disease in the hope of curing children with the misfortune of having one of these rare tumors.