Novel approach for efficient resonance tracking in photoacoustic gas sensor systems based on a light-induced wall signal.

Photoacoustic gas sensing is a method suited for the detection of radiation absorbing molecular species in the gas phase. Due to the backgroand-free detection, it has considerable benefits in the measurement of very low concentrations down to the parts-per-trillion range. Yet in resonant systems, the resonance frequency depends on several parameters like temperature or gas composition and therefore must be continuously determined. In the present work, we propose a new method of tracking the resonance frequency using a photoacoustic signal generated at the walls of the resonant cell. The method has been evaluated with two different photoacoustic setups intended for the detection of NO2. We further propose an algorithm for finding the resonance frequency and evaluated the performance thereof. With this method, it is possible to detect the resonance frequency of a cylindrical and a dumbbell-shaped cell in less than two seconds and with an accuracy < 0.06% and < 0.2%, respectively.

Open retropubic radical prostatectomy: Still a well-established surgical technique for prostate cancer management.

INTRODUCTION: The surgical treatment options for prostate cancer have changed rapidly, given the expansion of robotics. However, open retropubic radical prostatectomy (ORP) will continue to be performed in areas with financial limitations or with limited access to robotics. The purpose of this study was to determine the long-term oncological outcomes, to categorize complication rates and to examine the early continence rates in patients treated with ORP. METHODS: We identified all patients who underwent ORP at our institution between 2000 and 2020. A standardized pad test was used to determine the early continence rates upon catheter removal, the late continence around a year after surgery was determined by the number of pads per day. The Clavien-Dindo classification was used to report the complication rates. The biochemical recurrence (BCR)-free survival and overall survival (OS) rates were defined using the Kaplan-Meier method and log-rank analysis. Multivariable Cox-regression models were used to test the effect of different factors on biochemical recurrence. RESULTS: We analyzed 1095 patients. The median follow-up was 93.4 months. An overall 10-year BCR-free survival and OS of 73% and 82% respectively was found. A complication rate for Clavien Dindo≥3 was seen in 4.8% of patients. The early continence rate was 81.4% and the late continence 89,1%. Preoperative PSA level, Gleason score sum, pT stage, lymph node status, and surgical margin status were independent predictors of BCR (p<0.001, 95% CI). Limitations include retrospective and single center study design. CONCLUSIONS: ORP is a surgical procedure that provides excellent oncological- and early continence-rates.

Impact of urgent coronary artery bypass grafting on acute kidney injury : A matched cohort study.

OBJECTIVES: There is limited knowledge regarding the specific interrelationships between urgent coronary artery bypass graft (U-CABG) surgery and postoperative acute kidney injury (AKI). We aimed to (1) analyze the impact of urgent CABG (U-CABG) on the incidence and severity of postoperative AKI, (2) estimate the influence of AKI after U­CABG or elective CABG (E-CABG) on mortality and (3) identify risk factors for AKI depending on the urgency of operation. RESULTS: U­CABG patients showed a higher incidence of AKI (49.8% vs. E­CABG: 39.7%; p = 0.026), especially for higher AKI stages 2 + 3. In-hospital mortality was higher in U­CABG patients (12.6%) compared to E­CABG patients (2.3%; p < 0.001). The impact of AKI on mortality did not differ, but showed a strong coherency between higher AKI stages (2 + 3) and mortality (stage 1: OR 2.409, 95% CI 1.017-5.706; p = 0.046 vs. stage 2 + 3: OR 5.577; 95% CI 2.033-15.3; p = 0.001). Univariate logistic regression analysis revealed that preoperative renal impairment, peripheral vascular disease and transfusion of more than two red blood cell concentrates were predictors for postoperative AKI in both groups. CONCLUSIONS: U­CABG is a risk factor for postoperative AKI and even "mild" AKI leads to a significantly higher mortality. Hence, the prevention of modifiable risk factors might reduce the incidence of postoperative AKI and thus improve outcome.

Microencapsulated islet allografts in diabetic NOD mice and nonhuman primates.

OBJECTIVE: Our goal was to assess the efficacy of encapsulated allogeneic islets transplanted in diabetic NOD mice and streptozotocin (STZ)-diabetic nonhuman primates (NHPs). MATERIALS AND METHODS: Murine or NHP islets were microencapsulated and transplanted in non-immunosuppressed mice or NHPs given clinically-acceptable immunosuppressive regimens, respectively. Two NHPs were treated with autologous mesenchymal stem cells (MSCs) and peri-transplant oxygen therapy. Different transplant sites (intraperitoneal [i.p.], omental pouch, omental surface, and bursa omentalis) were tested in separate NHPs. Graft function was monitored by exogenous insulin requirements, fasting blood glucose levels, glucose tolerance tests, percent hemoglobin A1c (% HbA1c), and C-peptide levels. In vitro assessment of grafts included histology, immunohistochemistry, and viability staining; host immune responses were characterized by flow cytometry and cytokine/chemokine multiplex ELISAS. RESULTS: Microencapsulated islet allografts functioned long-term i.p. in diabetic NOD mice without immunosuppression, but for a relatively short time in immunosuppressed NHPs. In the NHPs, encapsulated allo-islets initially reduced hyperglycemia, decreased exogenous insulin requirements, elevated C-peptide levels, and lowered % HbA1c in plasma, but graft function diminished with time, regardless of transplant site. At necropsy, microcapsules were intact and non-fibrotic, but many islets exhibited volume loss, central necrosis and endogenous markers of hypoxia. Animals receiving supplemental oxygen and autologous MSCs showed improved graft function for a longer post-transplant period. In diabetic NHPs and mice, cell-free microcapsules did not elicit a fibrotic response. CONCLUSIONS: The evidence suggested that hypoxia was a major factor for damage to encapsulated islets in vivo. To achieve long-term function, new approaches must be developed to increase the oxygen supply to microencapsulated islets and/or identify donor insulin-secreting cells which can tolerate hypoxia.

Proteome changes in muscles, ganglia, and gills in Corbicula fluminea clams exposed to crude oil: Relationship with behavioural disturbances.

The use of online remote control for 24/7 behavioural monitoring can play a key role in estimating the environmental status of aquatic ecosystems. Recording the valve activity of bivalve molluscs is a relevant approach in this context. However, a clear understanding of the underlying disturbances associated with behaviour is a key step. In this work, we studied freshwater Asian clams after exposure to crude oil (measured concentration, 167 ± 28 µg·L-1) for three days in a semi-natural environment using outdoor artificial streams. Three complementary approaches to assess and explore disturbances were used: behaviour by high frequency non-invasive (HFNI) valvometry, tissue contamination with polycyclic aromatic hydrocarbons (PAH), and proteomic analysis. Two tissues were targeted: the pool adductor muscles - retractor pedal muscle - cerebral and visceral ganglia, which is the effector of any valve movement and the gills, which are on the frontline during contamination. The behavioural response was marked by an increase in valve closure-duration, a decrease in valve opening-amplitude and an increase in valve agitation index during opening periods. There was no significant PAH accumulation in the muscle plus nervous ganglia pool, contrary to the situation in the gills, although the latter remained in the low range of data available in literature. Major proteomic changes included (i) a slowdown in metabolic and/or cellular processes in muscles plus ganglia pool associated with minor toxicological effect and (ii) an increase of metabolic and/or cellular processes in gills associated with a greater toxicological effect. The nature of the proteomic changes is discussed in terms of unequal PAH distribution and allows to propose a set of explanatory mechanisms to associate behaviour to underlying physiological changes following oil exposure. First, the first tissues facing contaminated water are the inhalant siphon, the mantle edge and the gills. The routine nervous activity in the visceral ganglia should be modified by nervous information originating from these tissues. Second, the nervous activity in the visceral ganglia could be modified by its own specific contamination. Third, a decrease in nervous activity of the cerebral ganglia close to the mouth, including some kind of narcosis, could contribute to a decrease in visceral ganglia activity via a decrease or blockage of the downward neuromodulation by the cerebro-visceral connective. This whole set of events can explain the decrease of metabolic activity in the adductor muscles, contribute to initiate the catch mechanism and then deeply modify the valve behaviour.

Histopathology and Feline Pancreatic Lipase Immunoreactivity in Inflammatory, Hyperplastic and Neoplastic Pancreatic Diseases in Cats.

The most common pancreatic diseases in cats are pancreatitis and exocrine pancreatic insufficiency (EPI). Non-invasive methods, such as serological quantification of feline pancreatic lipase immunoreactivity (fPLI), are often used in the diagnosis of pancreatitis. Previous studies have compared fPLI concentrations with histopathology, considered to be the gold standard for diagnosis of feline pancreatitis. However, fPLI concentrations in cats suffering from pancreatic tumours were rarely described. The aim of the present study was to determine the sensitivity and specificity of an in-house enzyme-linked immunosorbent assay (ELISA) for the quantification of fPLI in serum samples based on histopathological findings in cats diagnosed with various pancreatic diseases. Pancreatic biopsy samples from 80 cats were included. Five groups were defined on the basis of pancreatic histopathology: group 1, normal pancreas; group 2, nodular hyperplasia; group 3, mild pancreatitis; group 4, marked (moderate/severe) pancreatitis; and group 5, pancreatic neoplasia. Serum samples from all cats were tested by fPLI ELISA (<3.6 µg/l normal, 3.6-5.3 µg/l questionable, >5.3 µg/l pancreatitis). In group 1 (n = 19), serum fPLI values were within the reference interval in 74% of cases and in group 2 (n = 9) in 78%. Cats with mild pancreatitis (n = 23), marked pancreatitis (n = 11) and pancreatic neoplasms (n = 18) had significantly increased fPLI concentrations compared with group 1 (P = 0.004/0.001/≤0.0001). Cats with nodular hyperplasia had significantly lower fPLI values than cats with marked pancreatitis (P = 0.048) or tumours (P = 0.002). Serum fPLI concentrations in group 3 were <3.6 µg/l (n = 6), 3.6-5.3 µg/l (n = 4) and >5.3 µg/l (n = 13). Calculated test sensitivity for mild pancreatitis was fPLI >3.5 µg/l: 73.9% and fPLI >5.3 µg/l: 56.5%. In group 4 (n = 11), seven of nine cats (77.8%) with marked purulent pancreatitis had elevated fPLI. In group 4, a sensitivity of 81.8% was detected for fPLI >3.5 µg/l and 63.6% for fPLI >5.3 µg/l. Two cats with marked non-purulent pancreatitis had elevated fPLI, while two cats with marked purulent pancreatitis had normal fPLI values (<3.6 µg/l). In group 5, one cat with pancreatic adenoma and one with pancreatic acinar carcinoma had normal fPLI concentrations. The other cats with pancreatic adenoma (solid, n = 1; cystic, n = 4) or carcinoma (solid, n = 9; cystic, n = 2) had elevated or high fPLI values (4.1 to >40 µg/l, median 21.2 µg/l), probably caused by additional inflammation. The results of the present study confirm the importance of detailed histopathological characterization for the interpretation of clinical signs and fPLI values in feline pancreatitis. Primary pancreatic neoplasms may also lead to elevated fPLI concentrations as there is concurrent pancreatitis in most cases. However, severe pancreatic diseases, such as chronic non-purulent pancreatitis or tumours without inflammation, may result in normal fPLI values.

Asiatic clam Corbicula fluminea exhibits distinguishable behavioural responses to crude oil under semi-natural multiple stress conditions.

Aquatic ecosystems are subject to many anthropogenic disturbances, and understanding their possible impacts is a real challenge. Developing approaches based on the behaviour of bivalve mollusks, an integrating marker of the state of the organisms, and therefore of their environment, is relevant, whether within a natural ecosystem or an ecosystem subject to industrial activities. The main objective of this study was to identify by HFNI Valvometry a reliable and reproducible clam behavioural response in the presence of crude oil in a multistress context. To closely replicate actual field conditions, Corbicula fluminea was exposed in outdoor artificial streams that were subject to natural variations and were continuously fed by fresh water from the Gave de Pau (S.W. France). After a period of 26 days in these artificial streams, the clams (n = 14-16 per condition) were separately exposed for 10 days to crude oil alone, crude oil and barium, crude oil and noise pollution, crude oil and turbidity pulses, barium alone, noise pollution alone, turbidity pulses alone or natural changes alone. The secondary objective was to characterize the accumulation of polycyclic aromatic hydrocarbons (PAH) in 3 tissues (gills, adductor muscles and foot) in clams exposed for 10 days to crude oil alone or under multistress conditions (n = 5 clams per condition) and then to compare the accumulation and behaviour of clams under these conditions. The response of clams to crude oil alone or under multistress conditions was visually and statistically significant and not confounded by the other disturbances tested, despite large variations in water temperature. In the presence of crude oil, the behaviour of clams was characterized by an increase in valve-closure duration, a decrease in valve-opening amplitude and an increase in valve agitation index. In the presence of crude oil, the clam behaviour showed no direct relationship with PAH accumulation in the gills, adductor muscles or foot, although hypothetical mechanisms are discussed. This work supports the growing interest in studying the behaviour of bivalve mollusks in the context of biomonitoring of the aquatic environment surrounding oil facilities.

Risk Factors Associated with In-Hospital Mortality for Patients with Acute Abdomen After Cardiac Surgery.

OBJECTIVES: Management of acute abdomen (AA) differs due to the heterogeneity of underlying pathophysiology. Complications of AA and its overall outcome after cardiac surgery are known to be associated with poor results. The aim of this retrospective analysis was to evaluate risk factors for AA in patients undergoing cardiac surgery. METHODS: Between December 2011 and December 2014, a total of 131 patients with AA after cardiac surgery were identified and retrospectively analyzed using our institutional database. Statistical analysis of risk factors concerning in-hospital mortality of mentioned patient cohort was performed using IBM SPSS Statistics. RESULTS: Overall in-hospital mortality was 54.2% (71/131). Analyzing in-hospital non-survivors (NS) versus in-hospital survivors (S) peripheral artery disease (28.2% vs. 11.7%; p = 0.03), the need for assist device therapy (33.8% vs. 16.7%; p = 0.03) and the requirement of hemodialysis (67.6% vs. 23.3%; p < 0.01) were significantly higher in NS. Furthermore, lactic acid values at onset of symptoms were shown to be significantly higher in NS (5.7 ± 5.7 mmol/L vs. 2.8 ± 2.9 mmol/L; p < 0.01). Assured diagnosis of mesenterial ischemia was strongly associated with worse outcome (odds ratio 10.800, 95% confidence interval 2.003-58.224; p = 0.006). CONCLUSION: In conclusion, in critically ill patients after performed cardiac surgery peripheral vascular disease, need for supportive hemodynamic assist device systems and occurrence of renal failure are risk factors associated with worsen outcome. Additionally, rise of lactic acid could potentially be associated with onset of intestinal malperfusion and should be taken into account in therapeutic decisions preventing fatal mesenterial ischemia.

Characterization of liver specific promoters in a foamy viral vector pMD09.

Foamy viruses (FVs) or spumaviruses are retroviruses that are explored as vectors for gene therapy. The good feature of foamy viruses is its broad tropism; however, their infections result in non-targeted gene expression. Here, we attempted to design the liver targeted viral gene delivery by employing liver specific gene promoters like albumin (ALB), transthyretin (TTR) and hepatitis B virus (HBV) promoters. We compared the relative gene expression of liver specific promoters versus the U3 promoter in liver cell line (HepG2) and non-liver cell lines: human fibrosarcoma cell line (HT1080), baby hamster kidney cell line (BHK), human embryonic kidney cell line (HEK 293T) and cervical cancer cell line (HeLa). We have found that the promoter exchange didn't affect viral assembly. The ability to drive gene expression was best with TTR promoter which was followed by HBV and ALB promoter. The use of TTR, HBV and ALB promoters are helpful in achieving liver specific gene expression. Keywords: foamy virus; gene therapy; liver; albumin; transthyretin promoter; HBV promoter.

Feasibility of Hyperfunctioning Parathyroid Gland Localization Using [18F]fluciclovine PET/CT.

PURPOSE: To evaluate the ability of anti-1-amino-3-anti-1-amino-3-[18F]fluorocyclobutane-1-carboxylic acid ([18F]fluciclovine) positron emission tomography/X-ray computed tomography (PET/CT) in comparison to Technetium-99m 2-methoxy isobutyl isonitrile ([99mTc]sestamibi) single-photon emission computed tomography/CT (SPECT/CT) for the localization of hyperfunctioning parathyroid glands in patients with hyperparathyroidism. PROCEDURES: Four patients with hyperparathyroidism underwent 60-minutes sequential neck and thorax PET/CT after [18F]fluciclovine (352 ± 28 MBq) injection. Lesion uptake and target-to-background ratios (TBR) were compared with [99mTc]sestamibi (798 ± 27 MBq) SPECT/CT in the same patient. RESULTS: Both techniques detected 4/5 hyperfunctioning parathyroid glands identified at surgery. The highest [18F]fluciclovine uptake and TBRs were at 5-9 min with rapid washout. [99mTc]sestamibi had significantly higher TBRs compared with [18F]fluciclovine (5-9 min) for blood pool (10.9 ± 4.7 vs 1.3 ± 0.6; p < 0.01) and reference muscle backgrounds (5.8 ± 3.0 vs 1.7 ± 0.6; p < 0.01), with non-significant trend for thyroid tissue background (1.3 ± 0.5 vs 1.1 ± 0.5; p = 0.73). CONCLUSION: Hyperfunctioning parathyroid glands can be detected on [18F]fluciclovine PET/CT at early imaging, but conspicuity (TBR) is better with [99mTc]sestamibi. [18F]fluciclovine PET/CT does not seem promising in the detection of hyperfunctioning parathyroid glands.

Is the humoral immunity dispensable for the pathogenesis of psoriasis?

BACKGROUND: Imbalances of T-cell subsets are hallmarks of disease-specific inflammation in psoriasis. However, the relevance of B cells for psoriasis remains poorly investigated. OBJECTIVE: To analyse the role of B cells and immunoglobulins for the disease-specific immunology of psoriasis. METHODS: We characterized B-cell subsets and immunoglobulin levels in untreated psoriasis patients (n = 37) and compared them to healthy controls (n = 20) as well as to psoriasis patients under disease-controlling systemic treatment (n = 28). B-cell subsets were analysed following the flow cytometric gating strategy based on the surface markers CD24, CD38 and CD138. Moreover, immunofluorescence stainings were used to detect IgA in psoriatic skin. RESULTS: We found significantly increased levels of IgA in the serum of treatment-naïve psoriasis patients correlating with disease score. However, IgA was only observed in dermal vessels of skin sections. Concerning B-cell subsets, we only found a moderately positive correlation of CD138+ plasma cells with IgA levels and disease score in treatment-naïve psoriasis patients. Confirming our hypothesis that psoriasis can develop in the absence of functional humoral immunity, we investigated a patient who suffered concomitantly from both psoriasis and a hereditary common variable immune defect (CVID) characterized by a lack of B cells and immunoglobulins. We detected variants in three of the 13 described genes of CVID and a so far undescribed variant in the ligand of the TNFRSF13B receptor leading to disturbed B-cell maturation and antibody production. However, this patient showed typical psoriasis regarding clinical presentation, histology or T-cell infiltrate. Finally, in a group of psoriasis patients under systemic treatment, neither did IgA levels drop nor did plasma cells correlate with IgA levels and disease score. CONCLUSION: B-cell alterations might rather be an epiphenomenal finding in psoriasis with a clear dominance of T cells over shifts in B-cell subsets.

Individual invitation letters lead to significant increase in attendance for screening colonoscopies: Results of a pilot study in Northern Hesse, Germany.

BACKGROUND: Colorectal cancer (CRC) is the second most common cancer in Germany. Screening colonoscopies are considered an effective tool for early detection and prevention of CRC and are recommended in Germany for citizens over the age of 55. To increase the participation rate for screening colonoscopies, an invitation procedure was initiated in parts of Germany for patients between the ages of 55 and 75 who had never undergone a screening colonoscopy before. METHODS: We examined the number of participating patients before, during, and after the invitation procedure and compared the number of the participating patients who received a cover letter with the participating patients from the control group. Additionally, we classified the findings of the colonoscopies including CRC, advanced adenomas, and polyps. RESULTS: During the invitation period, the participation rate of the invitation group increased from 220 patients to 531 patients compared to 1256 to 1693 in the control group. The increase was significantly greater in patients with cover letters (+141% vs.+35%, p < 0.0001). Also, significantly more polyps and adenomas were found in patients from the invitation letter group (254 (+102%) vs. 679 (-9%), p < 0.0001). CONCLUSIONS: Our study clearly indicates that personal invitation letters are an effective measure to increase overall participation rates in screening colonoscopies.

The JAK inhibitor ruxolitinib reduces inflammation in an ILC3-independent model of innate immune colitis.

Innate immunity contributes to the pathogenesis of inflammatory bowel disease (IBD). However, the mechanisms of IBD mediated by innate immunity are incompletely understood and there are limited models of spontaneous innate immune colitis to address this question. Here we describe a new robust model of colitis occurring in the absence of adaptive immunity. RAG1-deficient mice expressing TNFAIP3 in intestinal epithelial cells (TRAG mice) spontaneously developed 100% penetrant, early-onset colitis that was limited to the colon and dependent on intestinal microbes but was not transmissible to co-housed littermates. TRAG colitis was associated with increased mucosal numbers of innate lymphoid cells (ILCs) and depletion of ILC prevented colitis in TRAG mice. ILC depletion also therapeutically reversed established colitis in TRAG mice. The colitis in TRAG mice was not prevented by interbreeding to mice lacking group 3 ILC nor by depletion of TNF. Treatment with the JAK inhibitor ruxolitinib ameliorated colitis in TRAG mice. This new model of colitis, with its predictable onset and colon-specific inflammation, will have direct utility in developing a more complete understanding of innate immune mechanisms that can contribute to colitis and in pre-clinical studies for effects of therapeutic agents on innate immune-mediated IBD.

[Information services for melanoma patients and awareness among those affected]. / Informationsangebote für Melanompatienten und ihre Bekanntheit unter Betroffenen.

BACKGROUND: Besides medical consultations, various sources of information and support are available for melanoma patients (MP) in Germany from commercial and non-commercial providers; however, little is known about how they are perceived and accepted by MPs. MATERIAL AND METHODS: Between July and October 2016 a total of 529 melanoma patients were surveyed at 27 accredited German skin cancer centers by means of a standardized questionnaire. Their awareness and satisfaction with 12 given sources of information and counseling services (print, online and by telephone) were surveyed. The sources were recommended by renowned providers from the field of (dermatological) oncology for use by MPs. RESULTS: The MPs reported that the booklets called The blue advisor - skin cancer (Die Blauen Ratgeber - Hautkrebs, 43%) and Patient guidelines melanoma (Patientenleitlinie Melanom 24%) and the online domain www.hautkrebs-screening.de (23%) were the best known sources. These also met the information needs of the majority of users (65-80%). Booklets from commercial providers (between 8-16% known) were satisfactory for 42-56% of users. At 14% and 11%, respectively, the cancer counseling services (Krebsinformationsdienst) and INFONETZ Krebs as mainly telephone advisory offers were less well known. Few MPs were familiar with the skin cancer or melanoma booklets of the Austrian Cancer Aid and the Swiss Cancer League (2% each). CONCLUSION: The increased awareness and acceptance of booklets as well as information from principally non-commercial providers suggest that they are more often mediated to MPs and more frequently used and accepted by those affected.

Catecholamine crisis during induction of general anesthesia : A case report.

Catecholamine crises associated with pheochromocytoma may cause life-threatening cardiovascular conditions. We report the case of a 75-year-old male who developed a hypertensive crisis during induction of general anesthesia for elective resection of a cervical neuroma due to an undiagnosed pheochromocytoma. Hemodynamic instability occurred immediately after the injection of fentanyl, propofol and rocuronium, prior to laryngoscopy and in the absence of any manipulation of the abdomen. In this case report, we present the management of this incident and discuss the underlying pathophysiology triggering a catecholamine crisis.

Targeting prohibitins with chemical ligands inhibits KRAS-mediated lung tumours.

This corrects the article DOI: 10.1038/onc.2017.93.

Targeting prohibitins with chemical ligands inhibits KRAS-mediated lung tumours.

KRAS is one of the most frequently mutated oncogenes in human non-small cell lung cancers (NSCLCs). RAS proteins trigger multiple effector signalling pathways including the highly conserved RAF-MAPK pathway. CRAF, a direct RAS effector protein, is required for KRAS-mediated tumourigenesis. Thus, the molecular mechanisms driving the activation of CRAF are intensively studied. Prohibitin 1 (PHB1) is an evolutionarily conserved adaptor protein and interaction of CRAF with PHB1 at the plasma membrane is essential for CRAF activation. Here, we demonstrate that PHB1 is highly expressed in NSCLC patients and correlates with poor survival. Targeting of PHB1 with two chemical ligands (rocaglamide and fluorizoline) inhibits epidermal growth factor (EGF)/RAS-induced CRAF activation. Consistently, treatment with rocaglamide inhibited proliferation, migration and anchorage-independent growth of KRAS-mutated lung carcinoma cell lines. Surprisingly, rocaglamide treatment inhibited Ras-GTP loading in KRAS-mutated cells as well as in EGF-stimulated cells. Rocaglamide treatment further prevented the oncogenic growth of KRAS-driven lung cancer allografts and xenografts in mouse models. Our results suggest rocaglamide as a RAS inhibitor and that targeting plasma membrane-associated PHB1 with chemical ligands would be a viable therapeutic strategy to combat KRAS-mediated NSCLCs.

Development of a krypton-doped gas symmetry capsule platform for x-ray spectroscopy of implosion cores on the NIF.

The electron temperature at stagnation of an ICF implosion can be measured from the emission spectrum of high-energy x-rays that pass through the cold material surrounding the hot stagnating core. Here we describe a platform developed on the National Ignition Facility where trace levels of a mid-Z dopant (krypton) are added to the fuel gas of a symcap (symmetry surrogate) implosion to allow for the use of x-ray spectroscopy of the krypton line emission.

Patient reported outcomes in randomized controlled cancer trials in advanced disease: a structured literature review.

INTRODUCTION: In advanced cancer quality of life (QoL) is the most important goal of care. It is measured by patient-reported-outcomes (PRO). This structured review evaluated how randomized controlled trials (RCTs) on anti-cancer therapy in advanced cancer reported PRO. METHODS: Search was performed in MEDLINE via PubMed for RCTs with median patient survival of ≤2 years. Reporting was rated with the Consolidated Standards of Reporting Trials (CONSORT) PRO extension. RESULTS: Of 370 retrieved publications, 117 were eligible, but only 30/117 (26%) reported PRO. QoL was most frequently measured (29/30). On average, 4.4 (SD 2.5) of the 14 CONSORT items were met. CONCLUSION: PRO are insufficiently reported in advanced cancer trials. Yet, this is paramount to enable an informed and patient-oriented decision making process.

Newly acquired kiwi fruit allergy after bone marrow transplantation from a kiwi-allergic donor.

BACKGROUND: The phenomenon of allergy transfer from an allergic donor to a non-allergic recipient via hematopoietic cell transplantation has been described by several reports. However, it could not yet been conclusively shown that allergic reaction of the recipient is elicited by the donor's cells. OBJECTIVES: In the case of a 46-year-old male patient who - for the first time in his life - had two episodes of oral allergic syndrome upon kiwi consumption after having received myeloablative hematopoietic stem cell transplantation (HCT) from his kiwi-allergic sister, we aimed to clarify the origin of allergen reactive cells in the donor. We not only intended to demonstrate if allergy was transferred by HCT but also to present an experimental workup for the analysis of allergy transfer by HCT. METHODS: Allergic sensitization to kiwi in recipient and donor was proven by ImmunoCAP. Furthermore, origin of peripheral blood mononuclear cells (PBMCs) was analyzed by chromosomal fluorescence in situ hybridization (FISH). To confirm allergic reaction and activation of hematopoietic cells by customized kiwi extract, we performed basophil activation test from whole blood as well as T cell proliferation assays from purified PBMCs of both recipient and donor. RESULTS: Basophil activation upon kiwi extract was demonstrated in both recipient and donor. Besides, we showed proliferation of CD4(+) T cells after incubation with kiwi extract. FISH analysis proved that hematopoietic cells of the male recipient completely originated from the female donor. CONCLUSION: Exemplified in this patient, we show for the first time that allergy transfer is mediated by the donor's cells. Moreover, our experimental approach using customized kiwi extract to prove contribution of kiwi-specific T and B cells in both kiwi-allergic recipient and donor could serve as a model approach for future studies.