Medical Malpractice of Vestibular Schwannoma: A 40-Year Review of the United States Legal Databases.

OBJECTIVES:To analyze medical malpractice lawsuit trends pertaining to cases of vestibular schwannomas (VS). METHODS:Two major computerized legal databases (LexisNexis and WestLaw) were queried and reviewed for evaluation of all the US state and federal court records from civil trials alleging malpractice between 1976 and 2016. RESULTS:A total of 32 VS cases were identified. Allegations were divided into four categories: misdiagnosis/delayed diagnosis (47%), postoperative complications (44%), failure of informed consent or information sharing (16%), and other (3%). Postoperative complications included facial nerve paralysis, myocardial infarction, meningitis, and intracranial hemorrhage. Judgment amounts ranged from $300,000 to$2,000,000. The specialist type was specified for 24 of the 32 cases (75%): neurosurgeons (n = 9; 37%), neurotologists (n = 6; 25%), general otolaryngologists (n = 5; 21%), primary care physicians (n = 4; 17%), neurologists (n = 3; 12%), radiologists (n = 3; 12%), anesthesiologists (n = 2; 8%), radiation oncologists (n = 1; 4%), and general surgeon (n = 1; 4%). Of these 24 cases, (n = 9; 37%) two or more physicians were named as defendants in the lawsuit. CONCLUSIONS:Enhanced physician-patient communication, ensuring proper and adequate patient consent procedures, and proper documentation are good practices that may decrease the likelihood of lawsuits

A matter of science: the Massachusetts Institute of Technology and the transformation of American management education, 1950-1964

In 1950, General Motors chairman Alfred P. Sloan, Jr. approached MIT’s leaders about establishing a business school. The result was the School of Industrial Management (SIM), founded in 1952 and renamed in 1964 the MIT Sloan School of Management. During these early years the SIM’s leaders and faculty sought to create something extraordinary: a business school housed, grounded, and inspired by an institute of engi-neering and technology. They strived to apply new scientific techniques to the nascent field of industrial management and to American industrial firms that increasingly demanded rational, analytical, rigorously trained executives. They struggled to integrate the physical and social sciences into their education and research, helping to blaze a trail that long-established peers would not follow until the 1960s. And they strained to balance relevance with independence, colliding repeatedly with Sloan and other external advisors over a proper understanding of academic research, institutions, and cooperation with industry. By 1964 these efforts had developed a school at the forefront of business education’s “new look.” But as the extensive archival records demonstrate, it was never inevitable that they would succeed. Only by ongoing experimentation and agile diplomacy did the School become (in the words of the 1951 Deed of Gift) “a great center of research and education in the field of industrial management.” And although they helped transform management education through integrated, scientifically based study and teaching, the SIM’s deans, faculty, and leaders never found complete consensus on the extent to which industrial management was, in Alfred Sloan’s words, “a matter of science.”2018-06-22T00:00:00

Synthesis and (spectro)electrochemistry of mixedvalent diferrocenyl–dihydrothiopyran derivatives

Three novel diferrocenyl complexes were prepared and characterised. 2,2-Diferrocenyl-4,5-dimethyl- 3,6-dihydro-2H-thiopyran (1, sulphide) was accessible by the hetero-Diels–Alder reaction of diferrocenyl thioketone with 2,3-dimethyl-1,3-butadiene. Stepwise oxidation of 1 gave the respective oxides 2,2- diferrocenyl-4,5-dimethyl-3,6-dihydro-2H-thiopyran-1-oxide (2, sulfoxide) and 2,2-diferrocenyl-4,5- dimethyl-3,6-dihydro-2H-thiopyran-1,1-dioxide (3, sulfone), respectively. The molecular structures of 1 and 3 in the solid state were determined by single crystal X-ray crystallography. The oxidation of sulphide 1 to sulfone 3, plays only a minor role on the overall structure of the two compounds. Electrochemical (cyclic voltammetry (= CV), square wave voltammetry (= SWV)) and spectroelectrochemical (in situ UV-Vis/NIR spectroscopy) studies were carried out. The CV and SWV measurements showed that an increase of the sulphur atom oxidation from −2 in 1 to +2 in 3 causes an anodic shift of the ferrocenylbased oxidation potentials of about 100 mV. The electrochemical oxidation of 1–3 generates mixedvalent cations 1+–3+. These monooxidised species display low-energy electronic absorption bands between 1000 and 3000 nm assigned to IVCT (= Inter-Valence Charge Transfer) electronic transitions. Accordingly, the mixed-valent cations 1+–3+ are classified as weakly coupled class II systems according to Robin and Day.Authors (K. K. and G. M.) thank the National Science Centre (Poland) for financial support (Project Maestro-3; Dec-2012/06/ A/ST5/00219) and R. C. thanks the German Federal Ministry of Education and Research (BMBF) for support. The support from the German Academic Exchange Service (DAAD) in the framework of the exchange program “Ostpartnerschaften” is highly appreciated

Stimulation of the A2B adenosine receptor subtype enhances connexin26 hemichannel activity in small airway epithelial cells

Background/Aims: Adenosine release and connexin (Cx) hemichannel activity are enhanced in the respiratory epithelium during pathophysiological events such as inflammation. We analysed the interplay between Cx channels and adenosine signalling in human respiratory airway epithelium using the Calu-3 cell line as a model. Methods: The Cx hemichannel activity in Calu-3 cells was evaluated by dye uptake assays. The expressed Cx isoforms and adenosine receptor subtypes were identified by PCR and western blot analysis. Pharmacological and molecular biological experiments were performed to analyse the involvement of the different adenosine receptor subtypes, the induced signalling pathways and the contribution of specific Cx isoforms to the hemichannel activity. Results: The adenosine receptor agonist 5'-N-ethylcarboxamidoadenosine (NECA) increased the dye uptake rate in Calu-3 cells. The pannexon and Cx hemichannel inhibitor carbenoxolone (CBX) did not supress the dye uptake at pannexin-specific concentrations (100 µM). High CBX concentrations or the inhibitor La3+, both effective on Cx hemichannels, were needed to inhibit the dye uptake. The NECA-related increase of dye uptake depended on enhanced cAMP synthesis and subsequent activation of the protein kinase A (PKA) as shown by quantification of cAMP levels and pharmacological inhibition of the adenylyl cyclase and the PKA. Further pharmacological inhibition as well as knockdown experiments with specific siRNA showed that the A2B adenosine receptor was the subtype mainly responsible for the increased dye uptake. The NECA-related increase of the dye uptake rate correlated with a decrease of Cx43 mRNA and an increase of Cx26 mRNA content in the cells as well as Cx26 protein synthesis and was inhibited by Cx26 knockdown using Cx26 siRNA. Of note, a siRNA-induced knockdown of Cx43 increased the content of Cx26 mRNA and correspondingly the dye uptake rate. Conclusion: The Calu-3 cell model shows that stimulation of the A2B adenosine receptor subtype activates synthesis of cAMP. cAMP activates PKA and induces thereby an increase in Cx26 and a decrease in Cx43 mRNA levels. As a result, the synthesis of Cx26 is reinforced, leading to an enhanced Cx hemichannel activity. The report identifies a mechanism that integrates adenosine release and Cx hemichannel activity and shows how adenosine signalling and Cx channels may act together to promote persistent inflammation, which is observed in several chronic diseases of the respiratory airway

Parameters for Optoperforation-Induced Killing of Cancer Cells Using Gold Nanoparticles Functionalized With the C-terminal Fragment of Clostridium Perfringens Enterotoxin

Recently, we used a recombinant produced C-terminus (D194-F319) of the Clostridium perfringens enterotoxin (C-CPE) to functionalize gold nanoparticles (AuNPs) for a subsequent specific killing of claudin expressing tumor cells using the gold nanoparticle-mediated laser perforation (GNOME-LP) technique. For a future in vivo application, it will be crucial to know the physical parameters and the biological mechanisms inducing cell death for a rational adaptation of the system to real time situation. Regarding the AuNP functionalization, we observed that a relationship of 2.5 × 10−11 AuNP/mL to 20 µg/mL C-CPE maximized the killing efficiency. Regardingphysical parameters, a laser fluence up to 30 mJ/cm2 increased the killing efficiency. Independent from the applied laser fluence, the maximal killing efficiency was achieved at a scanning velocity of 5 mm/s. In 3D matrigel culture system, the GNOME-LP/C-CPE-AuNP completely destroyed spheroids composed of Caco-2 cells and reduced OE-33 cell spheroid formation. At the biology level, GNOME-LP/C-CPE-AuNP-treated cells bound annexin V and showed reduced mitochondria activity. However, an increased caspase-3/7 activity in the cells was not found. Similarly, DNA analysis revealed no apoptosis-related DNA ladder. The results suggest that the GNOME-LP/C-CPE-AuNP treatment induced necrotic than apoptotic reaction in tumor cells

Mutational landscape and predictors of survival in head and neck mucosal melanoma.

Head and neck mucosal melanomas have a diverse mutational landscape with low mutational burden. A molecular subset (∼13%) has ROS1 mutations, which is an actionable driver mutation. ROS1-mutated patients have improved overall survival likely due to high mutational burden

Molekularbiologische Diskriminierung zwischen planktonischen, Biofilm- und „Viable but non-culturable“-Zellen

Staphylococcus aureus und Staphylococcus epidermidis sind opportunistische Erreger biofilmassoziierter Infektionen. In Biofilmen gehen sie häufig in einen nicht kultivierbaren Zustand mit erhöhter Resilienz gegenüber schädlichen Umwelteinflüssen über (VBNC). Der VBNC-Zustand lässt sich in den untersuchten Stämmen durch die Inkubation in nährstofffreier Lösung mit einem milden pH-Stress induzieren. Eine molekularbiologische Diskriminierung von Zellen im VBNC-Zustand, Zellen im Biofilmverbund, planktonischen Zellen und toten Zellen ist anhand der Expressionsrate des 16S-Gens nicht möglich