Description: Background: A variety of multimodal treatment options are available for colorectal cancer and many patients want to be involved in decisions about their therapies. However, their desire for autonomy is limited by lack of disease-specific knowledge. Visual aids may be helpful tools to present complex data in an easy-to-understand, graphic form to lay persons. The aim of the present study was to evaluate the treatment preferences of healthy persons and patients using visual aids depicting multimodal treatment options for colorectal cancer. Methods: We designed visual aids for treatment scenarios based on four key studies concerning multimodal treatment of colorectal cancer. The visual aids were composed of diagrams depicting outcome parameters and side effects of two treatment options. They were presented to healthy persons (n = 265) and to patients with colorectal cancer (n = 102). Results: Most patients and healthy persons could make immediate decisions after seeing the diagrams (range: 88% -- 100%). Patients (79%) chose the intensive-treatment option in the scenario with a clear survival benefit. In scenarios without survival benefit, all groups clearly preferred the milder treatment option (range: 78% - 90%). No preference was seen in the scenario depicting equally intense treatment options with different timing (neoadjuvant vs. adjuvant) but without survival benefit. Conclusions: Healthy persons' and patients' decisions using visual aids seem to be influenced by quality-of-life aspects rather than recurrence rates especially in situations without survival benefit. In the future visual aids may help to improve the management of patients with colorectal cancer.

Description: Acetylation of lysine residues is an important posttranslational modification found in all domains of life. α-tubulin is specifically acetylated on lysine 40, a modification that serves to stabilize microtubules of axons and cilia. Whereas histone acetyltransferases have been extensively studied, there is no structural and mechanistic information available on α-tubulin...

Description: Background: Acute Otitis Media (AOM) is an important and common disease of childhood. Bacteria isolated from cases of clinically problematic AOM in German children were identified and characterized Methods: In a prospective non-interventional study in German children between 3 months and less than 60 months of age with Ear, Nose and Throat Specialist --confirmed AOM, middle ear fluid was obtained by tympanocentesis (when clinically indicated) or by careful sampling of otorrhea through/at an existing perforation. Results: In 100 children with severe AOM, Haemophilus influenzae was identified in 21% (18/21, 85.7% were non-typeable [NTHi]), Streptococcus pneumoniae in 10%, S. pyogenes in 13% and Moraxella catarrhalis in 1%. H. influenzae was the most frequently identified pathogen in children from 12 months of age. H. influenzae and S. pneumoniae were equally prevalent in children aged 3--11 months, but S. pyogenes was most frequently isolated in this age group. NTHi AOM disease appeared prevalent in all ages. Conclusions: NTHi, S. pneumoniae and S. pyogenes are implicated as important causes of complicated AOM in children in Germany. NTHi disease appears prevalent in all ages. The impact of vaccination to prevent NTHi and S. pneumoniae AOM may be substantial in this population and is worth investigating.

Description: Background: Treatment-naive patients newly diagnosed with HIV occasionally present with low viral RNA of

Description: Background: With the advent of percutaneous coronary intervention, specifically the bare metal stent and subsequently, the drug-eluting stent, the scope of interventional cardiology has greatly increased. Aspirin, in combination with a thienopyridine is the present-day cornerstone of oral antiplatelet therapy after coronary artery stent placement. Continuing this chronic antiplatelet therapy, to mitigate a perioperative major adverse cardiac event, can be challenging and remains controversial in patients with a coronary artery stent undergoing non-cardiac surgery. We describe here the rationale for and successful use of an alternate approach to formulating local institutional management protocols for patients with a coronary artery stent, undergoing an elective surgical procedure.DiscussionA recent systematic review identified 11 clinical practice guidelines for the perioperative management of antiplatelet therapy in patients with a coronary stent who need non-cardiac surgery. However, there is significant variance and inadequacy with these current applicable professional society guidelines. Moreover, persistently variable success has been experienced in translating even well-grounded national clinical guidelines into local practice, including in the perioperative setting. Under the auspices of a broadly multidisciplinary institutional task force and applying the Consensus-Oriented Decision-Making model, we created two evidence-informed and local expert opinion-supported standardized clinical assessment and management plans for the preoperative management of antiplatelet therapy in patients with a coronary artery stent.SummaryPatient care can be optimized via evidence-based, yet locally developed and reiterative standardized clinical assessment and management plans for patients with coronary artery stents undergoing surgical procedures. Such standardized clinical assessment and management plans can result in greater consistency in care, providing a positive feedback loop in which the care plan itself can be continuously reevaluated, improved, and brought up to date with the most recent available data and knowledge.

Description: Regulation of protein function is often linked to a conformational switch triggered by chemical or physical signals. To evaluate such conformational changes and to elucidate the underlying molecular mechanisms of subsequent protein function, experimental identification of conformational substates and characterization of conformational equilibria are mandatory. We apply pressure modulation in combination with FTIR spectroscopy to reveal equilibria between spectroscopically resolved substates of the lipidated signaling protein N-Ras. Pressure has the advantage that its thermodynamic conjugate is volume, a parameter that is directly related to structure. The conformational dynamics of N-Ras in its different nucleotide binding states in the absence and presence of a model biomembrane was probed by pressure perturbation. We show that not only nucleotide binding but also the presence of the membrane has a drastic effect on the conformational dynamics and selection of conformational substates of the protein, and a new substate appearing upon membrane binding could be uncovered. Population of this new substate is accompanied by structural reorientations of the G domain, as also indicated by complementary ATR-FTIR and IRRAS measurements. These findings thus illustrate that the membrane controls signaling conformations by acting as an effective interaction partner, which has consequences for the G-domain orientation of membrane-associated N-Ras, which in turn is known to be critical for its effector and modulator interactions. Finally, these results provide insights into the influence of pressure on Ras-controlled signaling events in organisms living under extreme environmental conditions as they are encountered in the deep sea where pressures reach the kbar range.

Description: Mutations in human leucine-rich-repeat kinase 2 (LRRK2) have been found to be the most frequent cause of late-onset Parkinson disease. Here we show that Dictyostelium discoideum Roco4 is a suitable model to study the structural and biochemical characteristics of the LRRK2 kinase and can be used for optimization of current and identification of new LRRK2 inhibitors. We have solved the structure of Roco4 kinase wild-type, Parkinson disease-related mutants G1179S and L1180T (G2019S and I2020T in LRRK2) and the structure of Roco4 kinase in complex with the LRRK2 inhibitor H1152. Taken together, our data give important insight in the LRRK2 activation mechanism and, most importantly, explain the G2019S-related increase in LRRK2 kinase activity.

Description: Atmospheric remote sensing has played a pivotal role in the increasingly sophisticated representation of clouds in the numerical models used to assess global and regional climate change. This has been accomplished because the underlying bulk cloud properties can be derived from a statistical analysis of the returned microwave signals scattered by a diverse ensemble comprised of numerous cloud hydrometeors. A new Doppler radar, previously used to track small debris particles shed from the NASA space shuttle during launch, is shown to also have the capacity to detect individual cloud hydrometeors in the free atmosphere. Similar to the traces left behind on film by subatomic particles, larger cloud particles were observed to leave a well-defined radar signature (or streak), which could be analyzed to infer the underlying particle properties. We examine the unique radar and environmental conditions leading to the formation of the radar streaks and develop a theoretical framework which reveals the regulating role of the background radar reflectivity on their observed characteristics. This main expectation from theory is examined through an analysis of the drop properties inferred from radar and in situ aircraft measurements obtained in two contrasting regions of an observed multicellular storm system. The observations are placed in context of the parent storm circulation through the use of the radar’s unique high-resolution waveforms, which allow the bulk and individual hydrometeor properties to be inferred at the same time.

Description: We recently reported the isolation of a scorpion toxin named U1-liotoxin-Lw1a (U1-LITX-Lw1a) that adopts an unusual 3D fold termed the disulfide-directed hairpin (DDH) motif, which is the proposed evolutionary structural precursor of the three-disulfide-containing inhibitor cystine knot (ICK) motif found widely in animals and plants. Here we reveal that U1-LITX-Lw1a...

Description: Background: Varied and fragmented care plans undertaken by different practitioners currently expose surgical patients to lapses in expected care, increase the chance for operational mistakes and accidents, and often result in unnecessary care. The Perioperative Surgical Home has thus been proposed by the American Society of Anesthesiologists and other stakeholders as an innovative, patient-centered, surgical continuity of care model that incorporates shared decision making. Topics central to the debate about an anesthesiology-based Perioperative Surgical Home include: holding the gains made in anesthesia-related patient safety; impacting surgical morbidity and mortality, including failure-to-rescue; achieving healthcare outcome metrics; assimilating comparative effectiveness research into the model; establishing necessary audit and data collection; a comparison with the hospitalist model of perioperative care; the perspective of the surgeon; the benefits of the Perioperative Surgical Home to the specialty of anesthesiology; and its associated healthcare economic advantages.DiscussionImproving surgical morbidity and mortality mandates a more comprehensive and integrated approach to the management of surgical patients. In their expanded capacity as the surgical patient's "perioperativist," anesthesiologists can play a key role in compliance with broader set of process measures, thus becoming a more vital and valuable provider from the patient, administrator, and payer perspective. The robust perioperative databases created within the Perioperative Surgical Home present new opportunities for health services and population-level research. The Perioperative Surgical Home is not intended to replace the surgeon's patient care responsibility, but rather leverage the abilities of the entire perioperative care team in the service of the patient. To achieve this goal, it will be necessary to expand the core knowledge, skills, and experience of anesthesiologists. Anesthesiologists will need to view becoming perioperative physicians as an expansion of the specialty, rather than an abdication of their traditional intraoperative role. The Perioperative Surgical Home will need to create strategic added value for a health system and payers. This added value will strengthen the position of anesthesiologists as they navigate and negotiate in the face of finite, if not decreasing fiscal resources.SummaryBroadening the anesthesiologist's scope of practice via the Perioperative Surgical Home may promote standardization and improve clinical outcomes and decrease resource utilization by providing greater patient-centered continuity of care throughout the preoperative, intraoperative, and postoperative periods.