Uncommon evolutions and complications of common benign liver lesions

Frequently encountered on abdominal imaging studies, the majority of common benign liver lesions are asymptomatic, confidently diagnosed by imaging, and do not require further workup, follow-up, or treatment. The increasing use of multimodality liver imaging, has allowed the recognition of uncommon evolutions of common benign liver lesions such as size changes, fibrotic regression, and content and vascularization changes, and their complications such as rupture, hemorrhage, thrombosis, extrinsic compression, and malignancy. The purpose of this pictorial review is to describe and illustrate the incidence and diagnostic features of these uncommon evolutions and complications on cross-sectional imaging, mainly on computed tomography and magnetic resonance imaging, with emphasis on those imaging clues which are helpful in the differential diagnosis or indicate the need for treatment

Temperature dependence of turnover in a Sc(OTf)3-catalyzed intramolecular Schmidt reaction Dedicated to the memory of Harry Wasserman, an inspirational person and a most elegant scholar

The intramolecular Schmidt reaction of ketones and tethered azides is an efficient method for the generation of amides and lactams. This reaction is catalyzed by Lewis acids, which tightly bind the strongly basic amide product and result in product inhibition. We report herein conditions to achieve a catalytic Schmidt reaction using substoichiometric amounts of the heat-stable Lewis acid Sc(OTf)3. This species was shown to effectively release products of the Schmidt reaction in a temperature-dependent fashion. Thus, heat was able to promote catalyst turnover. A brief substrate scope was conducted using these conditions

Overcoming product inhibition in catalysis of the intramolecular Schmidt reaction

A method for carrying out the intramolecular Schmidt reaction of alkyl azides and ketones using a substoichiometric amount of catalyst is reported. Following extensive screening, the use of the strong hydrogen-bond-donating solvent hexafluoro-2-propanol was found to be consistent with low catalyst loadings, which ranged from 2.5 mol % for favorable substrates to 25 mol % for more difficult cases. Reaction optimization, broad substrate scope, and preliminary mechanistic studies of this improved version of the reaction are described

Can they imagine the future? A qualitative study exploring the skills employers seek in pharmaceutical sciences doctoral graduates

Concerns about the extent to which graduate programs adequately prepare students for the workplace have prompted numerous calls for reform. Understanding what employers look for in doctoral graduates can help schools better align graduate training with workplace needs. Twelve pharmaceutical scientists across diverse specialties and career pathways described the skills considered requisite for success in today’s science economy. Depth and breadth of knowledge, communication, collaboration, adaptability, research productivity, experiential training, and motivation and drive were among the themes identified. These results can be used to inform the development of doctoral curricula in the biomedical sciences

(S)-N-(2,5-Dimethylphenyl)-1-(quinoline-8-ylsulfonyl)pyrrolidine-2-carboxamide as a Small Molecule Inhibitor Probe for the Study of Respiratory Syncytial Virus Infection

A high-throughput, cell-based screen was used to identify chemotypes as inhibitors for human respiratory syncytial virus (hRSV). Optimization of a sulfonylpyrrolidine scaffold resulted in compound 5o that inhibited a virus-induced cytopathic effect in the entry stage of infection (EC50 = 2.3 ± 0.8 µM) with marginal cytotoxicity (CC50 = 30.9 ± 1.1 µM) and reduced viral titer by 100-fold. Compared to ribavirin, sulfonylpyrrolidine 5o demonstrated an improved in vitro potency and selectivity index

Increased liver stiffness in patients with severe sleep apnoea and metabolic comorbidities

The goal of this study was to assess the relationship between the severity of obstructive sleep apnoea (OSA) and liver stiffness measurement (LSM), one of the most accurate noninvasive screening tools for liver fibrosis in nonalcoholic fatty liver disease.The study included 147 patients with at least one criterion for the metabolic syndrome, assessed by polysomnography for suspected OSA. LSM was performed using transient elastography (FibroScan). Significant liver disease and advanced liver fibrosis were defined as LSM ≥7.3 and ≥9.6 kPa, respectively.23 patients were excluded because of unreliable LSM. Among 124 patients, 34 (27.4%) had mild OSA, 38 (30.6%) had moderate OSA and 52 (42.0%) had severe OSA. LSM values were 7.3- <9.6 kPa in 18 (14.5%) patients and ≥9.6 kPa in 15 (12.1%) patients. A dose-response relationship was observed between OSA severity and LSM values (p=0.004). After adjustment for age, sex, metabolic syndrome and insulin resistance, severe OSA was associated with an increased risk of LSM ≥7.3 kPa (OR 7.17, 95% CI 2.51-20.50) and LSM ≥9.6 kPa (OR 4.73, 95% CI 1.25-17.88).In patients with metabolic comorbidities, severe OSA is independently associated with increased liver stiffness, which may predispose to a higher risk of significant liver disease and poorer prognosis

Tumor suppressor TET2 promotes cancer immunity and immunotherapy efficacy

Loss-of-function mutations in genes encoding TET DNA dioxygenase occur frequently in hematopoietic malignancy, but rarely in solid tumors, which instead commonly have reduced activity. The impact of decreased TET activity in solid tumors is not known. Here we show that TET2 mediates the IFN-γ/JAK/STAT signaling pathway to control chemokine and PD-L1 expression, lymphocyte infiltration, and cancer immunity. IFN-γ stimulated STAT1 to bind TET2 and recruit TET2 to hydroxymethylate chemokine and PD-L1 genes. Reduced TET activity was associated with decreased Th1-type chemokines and tumorinfiltrating lymphocytes and the progression of human colon cancer. Deletion of Tet2 in murine melanoma and colon tumor cells reduced chemokine expression and tumor-infiltrating lymphocytes, enabling tumors to evade antitumor immunity and to resist anti-PD-L1 therapy. Conversely, stimulating TET activity by systematic injection of its cofactor ascorbate/Vitamin C increased chemokines and tumor-infiltrating lymphocytes, leading to enhanced antitumor immunity and anti-PD-L1 efficacy and extended lifespan of tumor-bearing mice. These results suggest an IFN-γ/JAK/STAT/TET signaling pathway that mediates tumor response to anti-PD-L1/PD-1 therapy and is frequently disrupted in solid tumors. Our findings also suggest TET activity as a biomarker for predicting the efficacy of and patient response to anti-PD-1/PD-L1 therapy, and stimulation of TET activity as an adjuvant immunotherapy of solid tumors

Migraine aura or transient ischemic attacks? A five-year follow-up case-control study of women with transient central nervous system disorders in pregnancy

<p>Abstract</p> <p>Background</p> <p>Migraine aura may be difficult to differentiate from transient ischemic attacks and other transient neurological disorders in pregnant women. The aims of the present study were to investigate and diagnose all pregnant women with transient neurological disorders of suspected central nervous system origin, and to compare this group with a control group of pregnant women with regard to vascular risk factors and prognosis.</p> <p>Methods</p> <p>During a 28 month period, 41 patients were detected with transient neurological symptoms during pregnancy. These were studied in detail with thorough clinical and laboratory investigations in order to make a certain diagnosis and to evaluate whether the episodes might be of a vascular nature. For comparison, the same investigations were performed in 41 pregnant controls. To assess the prognosis, both patients and controls were followed with questionnaires every year for five years.</p> <p>Results</p> <p>Migraine with aura was the most common cause of symptoms during pregnancy, occurring in 34 patients, while 2 were diagnosed with stroke, 2 with carpal tunnel syndrome, 1 with partial epilepsy, 1 with multiple sclerosis and 1 with presyncope. Patients had more headache before pregnancy than controls, but the average levels of vascular risk factors were similar. None of the patients or the controls reported cerebrovascular episodes during the five-year follow-up.</p> <p>Conclusion</p> <p>The diagnosis of migraine aura was difficult because for many patients it was their first ever attack and headache tended to be absent or of non-migraineous type. The aura features were more complex, with several aura symptoms and a higher prevalence of sensory and dysphasic aura than usual. Gradually developing aura symptoms, or different aura symptoms occurring in succession as described in the International Classification of Headache Disorders, seem to be useful for differentiating aura from other transient disorders. A meticulous history and clinical neurological examination are more useful than routine supplementary investigations for cerebrovascular disease. The five-year follow-up clearly indicates that migraine with aura in pregnancy usually has a good prognosis with regard to cerebrovascular events.</p