Oligodendroglioma cells lack glutamine synthetase and are auxotrophic for glutamine, but do not depend on glutamine anaplerosis for growth

In cells derived from several types of cancer, a transcriptional program drives high consumption of glutamine (Gln), which is used for anaplerosis, leading to a metabolic addiction for the amino acid. Low or absent expression of Glutamine Synthetase (GS), the only enzyme that catalyzes de novo Gln synthesis, has been considered a marker of Gln-addicted cancers. In this study, two human cell lines derived from brain tumors with oligodendroglioma features, HOG and Hs683, have been shown to be GS-negative. Viability of both lines depends from extracellular Gln with EC of 0.175 ± 0.056 mM (Hs683) and 0.086 ± 0.043 mM (HOG), thus suggesting that small amounts of extracellular Gln are sufficient for OD cell growth. Gln starvation does not significantly affect the cell content of anaplerotic substrates, which, consistently, are not able to rescue cell growth, but causes hindrance of the Wnt/β-catenin pathway and protein synthesis attenuation, which is mitigated by transient GS expression. Gln transport inhibitors cause partial depletion of intracellular Gln and cell growth inhibition, but do not lower cell viability. Therefore, GS-negative human oligodendroglioma cells are Gln-auxotrophic but do not use the amino acid for anaplerosis and, hence, are not Gln addicted, exhibiting only limited Gln requirements for survival and growth

Single-session bridge-to-surgery choledochoduodenostomy and duodenal stenting in patient with malignant biliary and duodenal obstruction

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Pain treatment with high-dose, controlled-release oxycodone: an Italian perspective

To investigate the possible role and tolerability of high-dose (>160 mg/day) oxycodone controlled release (CR) for the treatment of cancer and non-cancer pain. 227 patients with cancer or non-cancer pain were enrolled in an open-label, multi-center, Italian study in order to assess the adequacy of their existing pain management (using a numerical rating scale [NRS]) and the possible benefit high-dose oxycodone CR may offer patients experiencing uncontrolled pain. Results: Pain was poorly controlled at baseline, with only 18.1% of patients reporting adequate pain relief (NRS <3.5). All other patients reported uncontrolled pain, with an average NRS of 7.81. At baseline assessment, 47.89% of patients had been in pain for up to 3 months, 32.82% for 3–6 months, and 19.19% for more than 6 months. After baseline assessment, patients were switched to oxycodone CR monotherapy. The starting dose was individualized to each patient and titrated up over a 3- to 4-day period until effective pain management was achieved. Treatment was continued for an average of 37.24 days during the study. Pain control (final mean NRS of 2.85) was attained with an average dose of oxycodone CR 221.84 mg/day. Standard adverse events (including constipations, nausea, and vomiting) were recorded in 39.64% of patients receiving high-dose oxycodone CR monotherapy. Side-effects tended to subside after the initial week of treatment and did not result in any participants leaving the study. High-dose oxycodone CR can achieve rapid and effective management of moderate to severe cancer and non-cancer pain with minimum side-effects

Feasibility and Accuracy of Transduodenal Endoscopic Ultrasound-Guided Fine-Needle Aspiration of Solid Lesions Using a 19-Gauge Flexible Needle: A Multicenter Study

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The emerging spectrum of cardiopulmonary pathology of the coronavirus disease 2019 (COVID-19): Report of 3 autopsies from Houston, Texas, and review of autopsy findings from other United States cities

This paper collates the pathological findings from initial published autopsy reports on 23 patients with coronavirus disease 2019 (COVID-19) from 5 centers in the United States of America, including 3 cases from Houston, Texas. Findings confirm that COVID-19 is a systemic disease with major involvement of the lungs and heart. Acute COVID-19 pneumonia has features of a distinctive acute interstitial pneumonia with a diffuse alveolar damage component, coupled with microvascular involvement with intra- and extravascular fibrin deposition and intravascular trapping of neutrophils, and, frequently, with formation of microthombi in arterioles. Major pulmonary thromboemboli with pulmonary infarcts and/or hemorrhage occurred in 5 of the 23 patients. Two of the Houston cases had interstitial pneumonia with diffuse alveolar damage pattern. One of the Houston cases had multiple bilateral segmental pulmonary thromboemboli with infarcts and hemorrhages coupled with, in nonhemorrhagic areas, a distinctive interstitial lymphocytic pneumonitis with intra-alveolar fibrin deposits and no hyaline membranes, possibly representing a transition form to acute fibrinous and organizing pneumonia. Multifocal acute injury of cardiac myocytes was frequently observed. Lymphocytic myocarditis was reported in 1 case. In addition to major pulmonary pathology, the 3 Houston cases had evidence of lymphocytic pericarditis, multifocal acute injury of cardiomyocytes without inflammatory cellular infiltrates, depletion of splenic white pulp, focal hepatocellular degeneration and rare glomerular capillary thrombosis. Each had evidence of chronic cardiac disease: hypertensive left ventricular hypertrophy (420 g heart), dilated cardiomyopathy (1070 g heart), and hypertrophic cardiomyopathy (670 g heart). All 3 subjects were obese (BMIs of 33.8, 51.65, and 35.2 Kg/

Late-term fetuses with reduced umbilical vein blood flow volume: An under-recognized population at increased risk of growth restriction

Objectives: To investigate the umbilical vein and uterine arteries blood flow volume (UV-Q, UtA-Q) in late-term pregnancies.& nbsp;Study design: This was a prospective observational cohort study of singleton pregnancies > 40 + 0 weeks in which UV-Q and UtA-Q, both absolute and normalized for estimated fetal weight (EFW) values, were evaluated in relation to AC drop of > 20 percentiles from 20 weeks to term, Doppler signs of fetal cerebral blood flow redistribution and composite adverse perinatal outcome. The presence of neonatal hypoglycaemia and the need of formula milk supplementation were also examined.& nbsp;Results: The study population comprised 200 women. Fetuses with AC drop (n = 34) had a significantly lower UV-Q and UV-Q/EFW than fetuses without AC drop (n = 166): median UV-Q 184 ml/min (IQR 143-225) vs 233 ml/min (IQR 181-277), p = 0.0006; median UV-Q/EFW 55 ml/min/kg (IQR 42-66) vs 63 ml/min/kg (IQR 48-74), p = 0.03. Fetuses with cerebral blood flow redistribution (n = 48) had a significantly lower UV-Q and UV-Q/EFW than those without (n = 134): median UV-Q 210 ml/min (IQR 155-263) vs 236 ml/min (IQR 184-278), p = 0.04; median UV-Q/EFV 58 ml/min/kg (IQR 45-70) vs 65 ml/min/kg (IQR 50-76), p = 0.04. There was a significant moderate correlation between middle cerebral artery pulsatility index (MCA-PI) and UV -Q and UV-Q/EFW (Spearman Rho-0.20 and-0.20; p = 0.008 and p = 0.006).& nbsp;Conclusions: The umbilical vein blood flow volume might have a potential role to identify fetuses with stunted growth in late-term pregnancies

Vector bundles on fano 3-folds without intermediate cohomology

A well known result of G. Horrocks [Proc. Lond. Math. Soc. (3) 14, 689-713 (1964; Zbl 0126.16801)] says that a vector bundle on a projective space has no intermediate cohomology if and only if it decomposes as a direct sum of line bundles. It is also known that only on projective spaces and quadrics there is, up to a twist by a line bundle, a finite number of indecomposable vector bundles with no intermediate cohomology [see R.-O. Buchweitz, G.-M. Greuel and F.-O. Schreyer, Invent. Math. 88, 165-182 (1987; Zbl 0617.14034) and also H. Kn¨orrer, Invent. Math. 88, 153-164 (1987; Zbl 0617.14033)]. In the paper under review the authors deal with vector bundles without intermediate cohomology on some Fano 3-folds with second Betti number b2 = 1. The Fano 3-folds they consider are smooth cubics in P4, smooth complete intersection of type (2, 2) in P5 and smooth 3-dimensional linear sections of G(1, 4) P9. A complete classification of rank two vector bundles without intermediate cohomology on such 3-folds is given. In fact the authors prove that, up to a twist, there are only three indecomposable vector bundles without intermediate cohomology. Vector bundles of rank greater than two are also considered. Under an additional technical condition, the authors characterize the possible Chern classes of such vector bundles without intermediate cohomology

Thalamocortical disconnection affects the somatic marker and social cognition: a case report

Thalamo-cortical connectivity was characterised in a patient with bilateral infarct of the thalami, without evidence of cognitive deficits in everyday life. Patient underwent social and emotional tests, Iowa Gambling Task (IGT), with and without concomitant heart rate variability (HRV) recording and at 3T-MRI to assess thalamo-cortical connectivity. Patient showed impairment at the IGT, in somatic marker, in emotions and theory of mind. MRI documented a bilateral damage of the centromedian-parafascicular complex. Patient's thalamic lesions disconnected brain areas involved in decision-making and autonomic regulation, affecting the somatic marker and resulting in the neuropsychological deficit exhibited by L.C