Revisiting cometary bow shock positions

The Rosetta spacecraft will arrive at comet 67P/Churyumov–Gerasimenko in 2014 and will escort the comet along its journey around the Sun. The predicted outgassing rate of the comet and the solar wind properties close to its perihelion at 1.24 AU lead to the expectation that a cometary bow shock will form during the escort phase. Since the forecasts of the subsolar stand off distances differ, this study revisits selected models and presents hybrid simulations of the comet–solar wind interaction region performed with the A.I.K.E.F. code. It is shown that small variations of the solar wind parameters will shift the bow shock position considerably. In addition, a model is presented that reproduces the bow shock distances observed in the hybrid simulations.

The free escape continuum of diffuse ions upstream of the Earth's quasi-parallel bow shock

The Earth's bow shock is very efficient in accelerating ions out of the incident solar wind distribution to high energies (≈ 200 keV/e). Fluxes of energetic ions accelerated at the quasi-parallel bow shock, also known as diffuse ions, are best represented by exponential spectra in energy/charge, which require additional assumptions to be incorporated into these model spectra. One of these assumptions is a so-called "free escape boundary" along the interplanetary magnetic field into the upstream direction. Locations along the IBEX orbit are ideally suited for in situ measurements to investigate the existence of an upstream free escape boundary for bow shock accelerated ions. In this study we use 2 years of ion measurements from the background monitor on the IBEX spacecraft, supported by ACE solar wind observations. The IBEX Background Monitor is sensitive to protons > 14 keV, which includes the energy of the maximum flux for diffuse ions. With increasing distance from the bow shock along the interplanetary magnetic field, the count rates for diffuse ions stay constant for ions streaming away from the bow shock, while count rates for diffuse ions streaming toward the shock gradually decrease from a maximum value to ~1/e at distances of about 10 RE to 14 RE. These observations of a gradual decrease support the transition to a free escape continuum for ions of energy >14 keV at distances from 10 RE to 14 RE from the bow shock.

A specific expression profile of heat-shock proteins and glucose-regulated proteins is associated with response to neoadjuvant chemotherapy in oesophageal adenocarcinomas

BACKGROUND Oesophageal adenocarcinomas often show resistances to chemotherapy (CTX), therefore, it would be of high interest to better understand the mechanisms of resistance. We examined the expression of heat-shock proteins (HSPs) and glucose-regulated proteins (GRPs) in pretherapeutic biopsies of oesophageal adenocarcinomas to assess their potential role in CTX response. METHODS Ninety biopsies of locally advanced adenocarcinomas before platin/5-fluorouracil (FU)-based CTX were investigated by reverse phase protein arrays (RPPAs), immunohistochemistry (IHC) and quantitative RT-PCR. RESULTS CTX response strongly correlated with survival (P=0.001). Two groups of tumours with specific protein expression patterns were identified by RPPA: Group A was characterised by low expression of HSP90, HSP27 and p-HSP27((Ser15, Ser78, Ser82)) and high expression of GRP78, GRP94, HSP70 and HSP60; Group B exhibited the inverse pattern. Tumours of Group A were more likely to respond to CTX, resulting in histopathological tumour regression (P=0.041) and post-therapeutic down-categorisation from cT3 to ypT0-T2 (P=0.040). High HSP60 protein (IHC) and mRNA expression were also associated with tumour down-categorisation (P=0.016 and P=0.004). CONCLUSION Our findings may enhance the understanding of CTX response mechanisms, might be helpful to predict CTX response and might have translational relevance as they highlight the role of potentially targetable cellular stress proteins in the context of CTX response.

Left ventricular torsion abnormalities in septic shock and corrective effect of volume loading: a pilot study

BACKGROUND Ventricular torsion is an important component of cardiac function. The effect of septic shock on left ventricular torsion is not known. Because torsion is influenced by changes in preload, we compared the effect of fluid loading on left ventricular torsion in septic shock with the response in matched healthy control subjects. METHODS We assessed left ventricular torsion parameters using transthoracic echocardiography in 11 patients during early septic shock and in 11 age- and sex-matched healthy volunteers before and after rapid volume loading with 250 mL of a Ringer's lactate solution. RESULTS Peak torsion and peak apical rotation were reduced in septic shock (10.2 ± 5.2° and 5.6 ± 5.4°) compared with healthy volunteers (16.3 ± 4.5° and 9.6 ± 1.5°; P = 0.009 and P = 0.006 respectively). Basal rotation was delayed and diastolic untwisting velocity reached its maximum later during diastole in septic shock patients than in healthy volunteers (104 ± 16% vs 111 ± 14% and 13 ± 5% vs 21 ± 10%; P = 0.03 and P = 0.034, respectively). Fluid challenge increased peak torsion in both groups (septic shock, 10.2 ± 5.3° vs 12.6 ± 3.9°; healthy volunteers, 16.3 ± 4.5° vs 18.1 ± 6°; P = 0.01). Fluid challenge increased left ventricular stroke volume in septic shock patients (P = 0.003). CONCLUSIONS Compared with healthy volunteers, left ventricular torsion is impaired in septic shock patients. Fluid loading attenuates torsion abnormalities in parallel with increasing stroke volume. Reduced torsional motion might constitute a relevant component of septic cardiomyopathy, a notion that merits further testing in larger populations.

Cardiac Shock Wave Therapy for Chronic Refractory Angina Pectoris. A Prospective Placebo-Controlled Randomized Trial

Background: Cardiac shock wave therapy (CSWT) delivered to the myocardium increases capillary density and regional myocardial blood flow in animal experiments. In addition, nonenzymatic nitric oxide production and the upregulation of vascular growth factor's mRNA by CSWT have been described. The aim of the study was therefore to test its potential to relieve symptoms in patients with chronic stable angina pectoris. Methods: Twenty-one patients (mean age 68.2 ± 8.3 years, 19 males) with chronic refractory angina pectoris and evidence of inducible myocardial ischemia during MIBI-SPECT imaging, were randomized into a treatment (n = 11) and a placebo arm (n = 10). The region of exercise-induced ischemia was treated with echocardiographic guidance during nine sessions over a period of 3 months. One session of CSWT consisted of 200 shots/spot (9--12 spots/session) with an energy intensity of 0.09 mJ/mm2. In the control group acoustic simulation was performed without energy application. Medication was kept unchanged during the whole treatment period. Results: In the treatment group, symptoms improved in 9/11 patients, and the ischemic threshold, determined by cardiopulmonary exercise stress testing, increased from 80 ± 28 to 95 ± 28 W (P= 0.036). In the placebo arm, only 2/10 patients reported an improvement and the ischemic threshold remained unchanged (98 ± 23 to 107 ± 23 W; P= 0.141). The items “physical functioning” (P= 0.043), “general health perception” (P= 0.046), and “vitality” (P= 0.035) of the SF-36 questionnaire significantly improved in the treatment arm, whereas in the placebo arm, no significant change was noted. Neither arrhythmias, troponin rise nor complications were observed during treatment. Conclusions: This placebo controlled trial shows a significant improvement in symptoms, quality of life parameters and ischemic threshold during exercise in patients with chronic refractory angina pectoris treated with CSWT. Thus, CSWT represents a new option for the treatment of patients with refractory AP.

Train your Brain - Psychotherapeutische Interventionsprogramme bei Angststörungen

Ängste und Depressionen gehören mitunter zu den häufigsten psychischen Störungen, die mit starkem individuellen Leiden und hohen sozioökonomischen Kosten einhergehen. Kulturell eingebettete biopsychosoziale Belastungsfaktoren tragen zur Entstehung, Aufrechterhaltung und Chronifizierung dieser häufigen Leiden bei. Moderne psychotherapeutische Interventionsprogramme können helfen, die individuellen Belastungsfaktoren besser zu ordnen, Vermeidungsverhalten zu durchbrechen und individuelles Wohlbefinden und psychosoziales Funktionieren zu fördern. Oftmals sind es kleine und feine Verhaltensänderungen im Alltag, die die subjektive Lebensqualität deutlich verbessern. Der Vortrag bietet eine kritische Übersicht über aktuelle psychotherapeutische Behandlungsansätze und deren empirische Evidenz.

Swiss Shock: Minaret Rejection, European Values, and the Challenge of Tolerant neutrality

In 2009 Switzerland, for long an apparent beacon of European toleration and neutrality, voted to ban the erection of minarets. Internal religious matters are normally dealt with at the regional or local level – not at the level of the Swiss national parliament, although the state does seek to ensure good order and peaceful relations between different faith communities. Indeed, the freedom of these communities to believe and function publicly is enshrined in law. However, as a matter of national policy, now constitutionally embedded, one religious group, the Muslim group, is not permitted to build their distinctive religious edifice, the minaret. Switzerland may have joined the rest of Europe with respect to engaging the challenge of Islamic presence to European identity and values, but the rejection of a symbol of the presence of one faith – in this case, Islamic – by a society that is otherwise predominantly secular, pluralist, and of Christian heritage, poses significant concerns. How and why did this happen? What are the implications? This paper will discuss some of the issues involved, concluding the ban is by no means irreversible. Tolerant neutrality may yet again be a leitmotif of Swiss culture and not just of foreign policy.

Effect of combined drought and heat stress on heat shock proteins in wheat varieties

Introduction: The re sponse of crop plants ex posed on drought or heat shock is related to de crease in the synthesis of normal proteins, accompanied by increased translation of heat shock proteins (HSPs). Though drought and heat stress have been studied individually, little is known about their combined effect on plants. Methods: The wheat (Triticum aestivum L.) varieties (Katya-tolerant, Sadovo or Mladka-susceptible) were potted in soil. Eight-day-old plants were ex posed to with drawing water for seven days. Heat shock was realized in growth chamber at 40 °C for 6h. A combination of drought and heat shock was per formed by subjecting drought-stressed plants to heat shock treatment. Expression of HSPs in the first leaf of wheat varieties was analyzed by SDS electrophoresis and immunoblotting. Polyclonal antibodies against HSP20, HSP60, HSP110 and mononclonal antibodies against HSP70 were used to distinguish the mentioned HSPs. Results: The leaf relative water content (RWC), which indicated the level of plant dehydration decreased significantly (34 %) under drought stressed conditions The electrolyte leakage of ions (EL), representing the level of the cell membrane stability in creased mark edly (68 %), especially under combination of drought and heat. Maximum EL was ob served in drought susceptible varieties Sadovo and Mladka. Drought and heat shock combination in the wheat plants resulted in the induction of specific HSPs. Conclusions: Our results demonstrate that the response of the wheat plants to a combination of drought and heat stress is different from the response of plants to each of these stresses applied separately. Induction of synergetic effect on HSP expression in case of combination between drought and heat was discussed in the case of two contrasting wheat varieties.

Extracorporeal shock wave therapy as a treatment of a non-healing chronic leg ulcer

Extracorporeal shock waves are defined as a sequence of sonic pulses characterized by high peak pressure over 100 MPa, fast pressure rise, and short lifecycle. In the 1980s extracorporeal shock wave lithotripsy (ESWL) was first used for the treatment of urolithiasis. Orthopedic surgeons use extracorporeal shock wave therapy (ESWT) to treat non-union fractures, tendinopathies and osteonecrosis. The first application of ESWT in dermatology was for recalcitrant skin ulcers. Several studies in the last 10 years have shown that ESWT promotes angiogenesis, increases perfusion in ischemic tissues, decreases inflammation, enhances cell differentiation and accelerates wound healing. We successfully treated a non-healing chronic venous leg ulcer with ESWT. Furthermore we observed an improvement of the lymphatic drainage after application of ESWT. We are confident that ESWT is a non-invasive, practical, safe and efficient physical treatment modality for recalcitrant leg ulcers.

Impact of epinephrine and norepinephrine on two dynamic indices in a porcine hemorrhagic shock model

Abstract BACKGROUND: Pulse pressure variations (PPVs) and stroke volume variations (SVVs) are dynamic indices for predicting fluid responsiveness in intensive care unit patients. These hemodynamic markers underscore Frank-Starling law by which volume expansion increases cardiac output (CO). The aim of the present study was to evaluate the impact of the administration of catecholamines on PPV, SVV, and inferior vena cava flow (IVCF). METHODS: In this prospective, physiologic, animal study, hemodynamic parameters were measured in deeply sedated and mechanically ventilated pigs. Systemic hemodynamic and pressure-volume loops obtained by inferior vena cava occlusion were recorded. Measurements were collected during two conditions, that is, normovolemia and hypovolemia, generated by blood removal to obtain a mean arterial pressure value lower than 60 mm Hg. At each condition, CO, IVCF, SVV, and PPV were assessed by catheters and flow meters. Data were compared between the conditions normovolemia and hypovolemia before and after intravenous administrations of norepinephrine and epinephrine using a nonparametric Wilcoxon test. RESULTS: Eight pigs were anesthetized, mechanically ventilated, and equipped. Both norepinephrine and epinephrine significantly increased IVCF and decreased PPV and SVV, regardless of volemic conditions (p < 0.05). However, epinephrine was also able to significantly increase CO regardless of volemic conditions. CONCLUSION: The present study demonstrates that intravenous administrations of norepinephrine and epinephrine increase IVCF, whatever the volemic conditions are. The concomitant decreases in PPV and SVV corroborate the fact that catecholamine administration recruits unstressed blood volume. In this regard, understanding a decrease in PPV and SVV values, after catecholamine administration, as an obvious indication of a restored volemia could be an outright misinterpretation.

Increased expression of heat shock protein 90 in keratinocytes and mast cells in patients with psoriasis.

BACKGROUND Psoriasis is a chronic inflammatory skin disease and various stress factors mediate inflammation. Heat shock protein (HSP) 90 plays an important role in cell survival; cytokine signaling, such as interleukin-17 receptor signaling; and immune responses. OBJECTIVE We sought to elucidate protein expression and distribution of HSP90 in psoriasis. METHODS HSP90 expression and its cellular source were analyzed on normal-appearing, nonlesional, lesional, and ustekinumab-treated psoriatic skin using immunohistochemistry and double immunofluorescence. RESULTS HSP90α, the inducible isoform of HSP90, was significantly up-regulated in epidermal keratinocytes and mast cells of lesional skin and down-regulated after ustekinumab therapy. LIMITATIONS There was a limited sample size. CONCLUSIONS HSP90 from keratinocytes and mast cells is a key regulator of psoriatic inflammation and HSP90 inhibitors may represent a novel therapeutic approach to the disease.

Drug-eluting stents vs. bare metal stents in patients with cardiogenic shock: a comparison by propensity score analysis.

BACKGROUND In patients with cardiogenic shock, data on the comparative safety and efficacy of drug-eluting stents (DESs) vs. bare metal stents (BMSs) are lacking. We sought to assess the performance of DESs compared with BMSs among patients with cardiogenic shock undergoing percutaneous coronary intervention (PCI). METHODS Out of 236 patients with acute coronary syndromes complicated by cardiogenic shock, 203 were included in the final analysis. The primary endpoint included death, and the secondary endpoint of major adverse cardiac and cerebrovascular events (MACCEs) included the composite of death, myocardial infarction, any repeat revascularization and stroke. Patients were followed for a minimum of 30 days and up to 4 years. As stent assignment was not random, we performed a propensity score analysis to minimize potential bias. RESULTS Among patients treated with DESs, there was a lower risk of the primary and secondary endpoints compared with BMSs at 30 days (29 vs. 56%, P < 0.001; 34 vs. 58%, P = 0.001, respectively) and during long-term follow-up [hazard ratio 0.43, 95% confidence interval (CI) 0.29-0.65, P < 0.001; hazard ratio 0.49, 95% CI 0.34-0.71, P < 0.001, respectively]. After propensity score adjustment, all-cause mortality was reduced among patients treated with DESs compared with BMSs both at 30 days [adjusted odds ratio (OR) 0.26, 95% CI 0.11-0.62; P = 0.002] and during long-term follow-up (adjusted hazard ratio 0.40, 95% CI 0.22-0.72; P = 0.002). The rate of MACCE was lower among patients treated with DESs compared with those treated with BMSs at 30 days (adjusted OR 0.42, 95% CI 0.19-0.95; P = 0.036). The difference in MACCEs between devices approached significance during long-term follow-up (adjusted hazard ratio 0.60, 95% CI 0.34-1.01; P = 0.052). CONCLUSION DESs appear to be associated with improved clinical outcomes, including a reduction in all-cause mortality compared with BMSs among patients undergoing PCI for cardiogenic shock, possibly because of a pacification of the infarct-related artery by anti-inflammatory drug. The results of this observational study require confirmation in an appropriately powered randomized trial.

Expression analysis of heat shock protein 90 (HSP90) and Her2 in colon carcinoma.

PURPOSE The molecular chaperone heat shock protein 90 (HSP90) plays an important role in several types of tumors also participating in the modulation of the activity of receptor tyrosine kinases activity such as members of the Her family. We evaluated the significance of HSP90 and Her2 expression in colon cancer. METHODS HSP90 and Her2 expression was determined by immunohistochemistry and by fluorescence in situ hybridization (FISH) on 355 primary resected colon carcinomas. Results were correlated with pathologic features (Union for International Cancer Control (UICC) pTNM category, tumor localisation, tumor differentiation), additional molecular genetic characteristics (BRAF, KRAS mutational status, mismatch repair genes (MMR)), and survival. RESULTS HSP90 immunoreactivity was observed in various degrees. Fifty-one cases (14 %) were positive for Her2 (score 2+ and 3+) with 16/43 cases with Her2 2+ staining pattern showing amplification of Her2 determined by FISH. There was a significant correlation between high HSP90 expression and Her2 overexpression (p = 0.011). High HSP90 expression was associated with earlier tumor stages (p = 0.019), absence of lymph node (p = 0.006), and absence of distant metastases (p = 0.001). Patients with high tumoral HSP90 levels had a better survival (p = 0.032), but this was not independent from other prognostic relevant pathologic parameters. Her2 expression was not associated with any of the investigated histopathological, molecular, or clinical parameters. CONCLUSIONS High HSP90 levels are reflecting lower malignant potential in colon cancer. Her2 positivity can be observed in a small number of cases. Targeting HSP90 and/or Her2 may be an alternative therapeutic approach in colon cancer in a subset of patients.