Mutational and gene fusion analyses of primary large cell and large cell neuroendocrine lung cancer

Large cell carcinoma with or without neuroendocrine features (LCNEC and LC, respectively) constitutes 3–9% of non-small cell lung cancer but is poorly characterized at the molecular level. Herein we analyzed 41 LC and 32 LCNEC (including 15 previously reported cases) tumors using massive parallel sequencing for mutations in 26 cancer-related genes and gene fusions in ALK, RET, and ROS1. LC patients were additionally subdivided into three immunohistochemistry groups based on positive expression of TTF-1/Napsin A (adenocarcinoma-like, n = 24; 59%), CK5/P40 (squamous-like, n = 5; 12%), or no marker expression (marker-negative, n = 12; 29%). Most common alterations were TP53 (83%), KRAS (22%), MET (12%) mutations in LCs, and TP53 (88%), STK11 (16%), and PTEN (13%) mutations in LCNECs. In general, LCs showed more oncogene mutations compared to LCNECs. Immunomarker stratification of LC revealed oncogene mutations in 63% of adenocarcinoma-like cases, but only in 17% of marker-negative cases. Moreover, marker-negative LCs were associated with inferior overall survival compared with adenocarcinoma-like tumors (p = 0.007). No ALK, RET or ROS1 fusions were detected in LCs or LCNECs. Together, our molecular analyses support that LC and LCNEC tumors follow different tumorigenic paths and that LC may be stratified into molecular subgroups with potential implications for diagnosis, prognostics, and therapy decisions.     

Functional impact of subthalamotomy by magnetic resonance–guided focused ultrasound in Parkinson’s disease: a hybrid PET/MR study of resting-state brain metabolism

European Journal of Nuclear Medicine and Molecular Imaging - Subthalamotomy using magnetic resonance–guided focused ultrasound (MRgFUS) has become a potential treatment option for the...     

One-pot synthesis of formic acid via hydrolysis–oxidation of potato starch in the presence of cesium salts of heteropoly acid catalysts

Solid bifunctional catalysts based on cesium salts of V-containing heteropoly acids (CsHPA: Cs_3.5H_0.5PW₁₁VO₄₀, Cs_4.5H_0.5SiW₁₁VO₄₀, Cs_3.5H_0.5PMo₁₁VO₄₀) and Cs_2.5H_0.5PMo₁₂O₄₀ were used for studying one-pot hydrolysis–oxidation of potato starch to formic acid at 413–443 K and 2 MPa air mixture. It was shown that the optimum process temperature that prevents formic acid from destruction is 423 K. The studies were focused on the influence of the composition of heteropoly anions on the yield and selectivity of formic acid. Using W–V–P(Si) CsHPA results in the product overoxidation compared to Mo–V-containing CsHPA. The activity of Cs–PMo was significantly lower compared to Cs–PMoV. This may indicate that vanadium plays an important role in the oxidation process. The most promising catalyst was Cs_3.5H_0.5PMo₁₁VO₄₀ which provided the maximum yield of formic acid equal to 51%. Cs_3.5H_0.5PMo₁₁VO₄₀ was tested during nine cycles of starch hydrolysis–oxidation to demonstrate its high stability and efficiency.

Influence of composition of catalysts based on heteropoly acid cesium salts on formic acid production via starch hydrolysis–oxidation was investigated.     

Autoimmune polyendocrine syndrome type 1: Utility of KCNRG autoantibodies as a marker of active pulmonary disease and successful treatment with rituximab

Autoimmune polyendocrine syndrome type 1 (APS-1), also known as Autoimmune Polyendocrinopathy Candidiasis and Ectodermal Dysplasia (APECD) is a disorder caused by mutations in the autoimmune regulator (AIRE) gene. In some APS-1 patients, significant pulmonary disease is observed. Autoantibodies directed against the potassium channel regulatory protein (KCNRG), found in epithelial cells of terminal bronchioles, have been suggested as a marker for pulmonary disease in APS-1 patients. We report two patients with APS-1; one with and one without lung disease. Patient 1 had multiple admissions for pneumonia and respiratory insufficiency, required non-invasive ventilation, and had findings of bronchiectasis on thoracic imaging and significant lymphocytic infiltrates of the airways on lung biopsy. To verify the autoimmune cause of pulmonary symptoms APS-1 patients, both were tested in a blinded manner for the presence of autoantibodies to KCNRG in serum. We found that only Patient 1 had autoantibodies present. Additionally, Patient 1 had progressive disease despite treatment with several immunomodulating agents, including corticosteroids, azathioprine, and mycophenolate. Patient 1 had a lung biopsy performed which was consistent with B cell lymphocytic aggregates. Rituximab treatment was initiated with apparent good response. This report illustrates the practical use of KCNRG autoantibodies to identify APS-1 patients with pulmonary risk and the successful use of the monoclonal antibody, Rituximab, to treat pulmonary disease in APS-1 patients.     

Effects of a Lacto-Ovo-Vegetarian Diet on the Plasma Lipidome and Its Association with Atherosclerotic Burden in Patients with Coronary Artery Disease—A Randomized,Open-Label,Cross-over Study

A vegetarian diet has been associated with a lower risk of coronary artery disease (CAD). Plasma triacylglycerols, ceramides, and phosphatidylcholines may improve prediction of recurrent coronary events. We sought to investigate effects of a lacto-ovo-vegetarian diet (VD) on plasma lipidome in CAD patients and simultaneously assess associations of plasma lipids with the extent of coronary atherosclerotic burden. We analyzed 214 plasma lipids within glycerolipid, sphingolipid, and sterol lipid classes using lipidomics from a randomized controlled, crossover trial comprising 31 CAD patients on standard medical therapy. Subjects completed a four-week intervention with VD and isocaloric meat diet (MD), separated by a four-week washout period. The VD increased levels of 11 triacylglycerols and lowered 7 triacylglycerols, 21 glycerophospholipids, cholesteryl ester (18:0), and ceramide (d18:1/16:0) compared with MD. VD increased triacylglycerols with long-chain polyunsaturated fatty acyls while decreased triacylglycerols with saturated fatty acyls, phosphatidylcholines, and sphingomyelins than MD. The Sullivan extent score (SES) exhibited on coronary angiograms were inversely associated with triacylglycerols with long-chain polyunsaturated fatty acyls. Phosphatidylcholines that were lower with VD were positively associated with SES and the total number of stenotic lesions. The VD favorably changed levels of several lipotoxic lipids that have previously been associated with increased risk of coronary events in CAD patients.     

Cortisol variability and self‐reports in the measurement of work‐related stress

We examined whether a high cortisol awakening response (CAR) and low cortisol decline over the day (CDD) are related to self‐reported work stress and well‐being, and whether there are gender differences in these relationships. Three hundred eighty‐three working men and women responded to a survey measuring job stress factors, mastery at work, symptoms and well‐being. Salivary cortisol was sampled at awakening, after 45 min and at 21:00, from which the variables CAR and CDD were defined. A high CAR was associated with lower perceived job control and work mastery, and poorer well‐being. Low CDD was associated only with higher job demands, but the self‐report scores showed a number of interactions between cortisol group and gender. Among women, those showing a low CDD, compared with those with a higher CDD, had more favourable scores on a number of job stress factors and symptom load. In contrast, among men, a similar comparison showed those with low CDD to have poorer scores on job stress factors and symptom load. We conclude that individuals displaying high CAR or low CDD differ from those not displaying these cortisol profiles in self‐report of work stress and well‐being, and that gender differences appear in these relationships. Copyright © 2010 John Wiley & Sons, Ltd.     

The burden of alcohol on health care during COVID-19

Alcohol's impact on global health is substantial and of a similar order of magnitude to that from COVID-19. Alcohol now also poses specific concerns, such as increased risk of severe lung infections, domestic violence, child abuse, depression and suicide. Its use is unlikely to aid physical distancing or other preventative behavioural measures. Globally, alcohol contributes to 20% of injury and 11.5% of non-injury emergency room presentations. We provide some broad comparisons between alcohol-attributable and COVID-19-related hospitalisations and deaths in North America using most recent data. For example, for Canada in 2017 it was recently estimated there were 105 065 alcohol-attributable hospitalisations which represent a substantially higher rate over time than the 10 521 COVID-19 hospitalisations reported during the first 5 months of the pandemic. Despite the current importance of protecting health-care services, most governments have deemed alcohol sales to be as essential as food, fuel and pharmaceuticals. In many countries, alcohol is now more readily available and affordable than ever before, a situation global alcohol producers benefit from and have helped engineer. We argue that to protect frontline health-care services and public health more generally, it is essential that modest, evidence-based restrictions on alcohol prices, availability and marketing are introduced. In particular, we recommend increases in excise taxation coupled with minimum unit pricing to both reduce impacts on health-care services and provide much-needed revenues for governments at this critical time.