bluuebunny/crossref_metadata_2025 huggingface dataset:
Managing daily intensive care activities: An observational study concerning ad hoc decision making of charge nurses and intensivists
Authors: Lundgrén-Laine Heljä , Kontio Elina , Perttilä Juha , Korvenranta Heikki , Forsström Jari , Salanterä Sanna
Published: August 2011

Introduction

Management of daily activities in ICUs is challenging. ICU shift leaders, charge nurses and intensivists have to make several immediate ad hoc decisions to enable the fluent flow of ICU activities. Even though the management of ICU activities is quite well delineated by international consensus guidelines, we know only a little about the content of the real clinical decision making of ICU shift leaders.

Methods

We conducted an observational study with the think-aloud technique to describe the ad hoc decision making of ICU shift leaders. The study was performed in two university-affiliated hospital ICUs. Twelve charge nurses and eight intensivists were recruited. Observations were recorded and transcribed for qualitative content analysis using the protocol analysis method. The software program NVivo 7 was used to manage the data. The interrater agreement was assessed with percentages and by Cohen's κ.

Results

We identified 463 ad hoc decisions made by the charge nurses and 444 made by the intensivists. During our data collection time, this breaks down to over 230 immediately made decisions per day (24 hours). We divided the ad hoc decision making of ICU shift leaders into two types: process-focused and situation-focused. Process-focused decision making included more permanent information, such as human resources, know-how and material resources, whereas situation-focused decision making included decisions about single events, such as patient admission. We named eight different categories for ICU ad hoc decision making: (1) adverse events, (2) diagnostics, (3) human resources and know-how, (4) material resources, (5) patient admission, (6) patient discharge, (7) patient information and vital signs and (8) special treatments.

Conclusions

ICU shift leaders make a great number of complex ad hoc decisions throughout the day. Often this decision making involves both intensivists and charge nurses. It forms a bundle that requires versatile, immediate information for a successful outcome. In the future, we need to investigate which information is crucial for ad hoc decision making. These challenges should also be emphasised when information technology programs for ICU care management are developed.
Specific Training Program Improves Oncologists' Palliative Care Communication Skills in a Randomized Controlled Trial
Authors: Goelz Tanja , Wuensch Alexander , Stubenrauch Sara , Ihorst Gabriele , de Figueiredo Marcelo , Bertz Hartmut , Wirsching Michael , Fritzsche Kurt
Published: August 2011

Purpose

The aim of the study was to demonstrate that COM-ON-p, concise and individualized communication skills training (CST), improves oncologists' communication skills in consultations focusing on the transition to palliative care.

Methods

Forty-one physicians were randomly assigned to a control (CG) or intervention group (IG). At t0, all physicians held two video-recorded consultations with actor-patient pairs. Afterward, physicians in the IG participated in COM-ON-p. Five weeks after t0, a second assessment took place (t1). COM-ON-p consists of an 11-hour workshop (1.5 days), pre- and postassessment (2 hours), and coaching (0.5 hours). Physicians focused on practicing individual learning goals with actor patients in small groups. To evaluate the training, blinded raters assessed communication behavior of the physicians in video-recorded actor-patient consultations using a specific checklist. Data were analyzed using a mixed model with baseline levels as covariates.

Results

Participants in the IG improved significantly more than those in the CG in all three sections of the COM-ON-Checklist: skills specific to the transition to palliative care, global communication skills, and involvement of significant others (all P < .01). Differences between the CG and IG on the global items of communication skills and involvement of significant others were also significant (P < .01). Effect sizes were medium to large, with a 0.5-point improvement on average on a five-point rating scale.

Conclusion

Physicians can be trained to meet better core challenges during the transition to palliative care through developed concise CST. Generalization and transfer into clinical practice must be proven in additional studies.
Natural Course of Insomnia Comorbid With Cancer: An 18-Month Longitudinal Study
Authors: Savard Josée , Ivers Hans , Villa Julie , Caplette-Gingras Aude , Morin Charles M.
Published: August 2011

Purpose

This study aimed to assess the prevalence and natural course (incidence, persistence, remission, and relapse) of insomnia comorbid with cancer during an 18-month period.

Patients and Methods

All patients scheduled to receive a curative surgery for a first diagnosis of nonmetastatic cancer were approached on the day of their preoperative visit to participate in the study. A total of 962 patients with cancer (mixed sites) completed an insomnia diagnostic interview at the perioperative phase (T1), as well as at 2 (T2), 6 (T3) 10 (T4), 14 (T5), and 18 (T6) months after surgery.

Results

Findings revealed high rates of insomnia at baseline (59%), including 28% with an insomnia syndrome. The prevalence of insomnia generally declined over time but remained pervasive even at the end of the 18-month period (36%). Rates were greater in patients with breast (42% to 69%) and gynecologic (33% to 68%) cancer and lower in men with prostate cancer (25% to 39%) throughout the study. Nearly 15% of patients had a first incidence of insomnia during the study, and 19.5% experienced relapse. The evolution of symptoms varied according to sleep status. Remissions (patients becoming good sleepers) were much less likely for patients with an insomnia syndrome (10.8% to 14.9%) than for those with insomnia symptoms (42.0% to 51.3%). Most frequently (37.6%), patients with an insomnia syndrome at baseline kept that status throughout the 18-month period.

Conclusion

Insomnia is a frequent and enduring problem in patients with cancer, particularly at the syndrome level. Early intervention strategies, such as cognitive-behavioral therapy, could prevent the problem from becoming more severe and chronic.
Active Surveillance for Prostate Cancer: Progress and Promise
Authors: Cooperberg Matthew R. , Carroll Peter R. , Klotz Laurence
Published: August 2011

Widespread prostate-specific antigen (PSA) –based screening and aggressive treatment of prostate cancer have reduced mortality rates substantially, but both remain controversial in large part because of high rates of overdiagnosis and overtreatment of otherwise indolent tumors. Active surveillance—or close monitoring of PSA levels combined with periodic imaging and repeat biopsies—is gaining acceptance as an alternative initial management strategy for men with low-risk prostate cancer. In reported series, rates of progression to active treatment with intermediate-term follow-up have ranged from 14% to 41%, and likelihood of subsequent cure with surgery or radiation does not seem to be compromised by an initial trial of surveillance. Two related challenges to broader acceptance of surveillance are better characterization at time of diagnosis of the risk of progression (including likelihood that given tumor may have been undersampled by diagnostic biopsy) and validation of optimal end points once surveillance begins. Both are subjects of intense ongoing investigation, with emerging biomarkers and novel imaging tests expected to facilitate decision making substantially. Recent reports have suggested active surveillance can be a cost-effective approach and preserve quality of life, but these questions must be assessed more definitively in prospective cohorts. Ultimately, by minimizing the harms of overtreating low-risk prostate cancer, active surveillance may help settle the controversy surrounding prostate cancer screening and management.
Clinical Features and Outcome of Patients With Non–Small-Cell Lung Cancer Harboring BRAF Mutations
Authors: Marchetti Antonio , Felicioni Lara , Malatesta Sara , Grazia Sciarrotta Maria , Guetti Luigi , Chella Antonio , Viola Patrizia , Pullara Carmela , Mucilli Felice , Buttitta Fiamma
Published: August 2011

Purpose

To investigate the prevalence, distribution, and prognostic role of BRAF mutations in a large cohort of white patients with non–small-cell lung cancer (NSCLC).

Patients and Methods

A retrospective series of 1,046 NSCLCs—comprising 739 adenocarcinomas (ADCs) and 307 squamous cell carcinomas (SCCs)—was investigated for BRAF mutations. High-resolution melting analysis followed by sequencing and strip hybridization assay were used. All patients were also analyzed for KRAS and EGFR mutations.

Results

BRAF mutations were present in 36 ADCs (4.9%) and one SCC (0.3%; P = .001). Twenty-one of the mutations (56.8%) were V600E, and 16 (43.2%) were non-V600E. V600E mutations were significantly more prevalent in females (16 of 187 patients; 8.6%) than in males (five of 552 patients; 0.9%), as indicated by multivariate logistic regression analysis (hazard ratio [HR], 11.29; P < .001). V600E-mutated tumors showed an aggressive histotype characterized by micropapillary features in 80% of patients and were significantly associated with shorter disease-free and overall survival rates on both univariate (HR, 2.67; P < .001 and HR, 2.97; P < .001, respectively) and multivariate analyses (HR, 2.19; P = .011 and HR, 2.18; P = .014, respectively). All non-V600E mutations were found in smokers (P = .015) and were associated with neither clinicopathologic parameters nor prognosis. BRAF and EGFR were concomitantly mutated in two tumors.

Conclusion

We report for the first time to our knowledge that V600E and non-V600E BRAF mutations affect different patients with NSCLC. V600E mutations are significantly associated with female sex and represent a negative prognostic factor. In addition, we identified a number of other clinicopathologic parameters potentially useful for the selection of patients carrying BRAF mutations.
Inflammation and Behavioral Symptoms After Breast Cancer Treatment: Do Fatigue, Depression, and Sleep Disturbance Share a Common Underlying Mechanism?
Authors: Bower Julienne E. , Ganz Patricia A. , Irwin Michael R. , Kwan Lorna , Breen Elizabeth C. , Cole Steve W.
Published: August 2011

Purpose

Fatigue, depression, and sleep disturbance are common adverse effects of cancer treatment and frequently co-occur. However, the possibility that inflammatory processes may underlie this constellation of symptoms has not been examined.

Patients and Methods

Women (N = 103) who had recently finished primary treatment (ie, surgery, radiation, chemotherapy) for early-stage breast cancer completed self-report scales and provided blood samples for determination of plasma levels of inflammatory markers: soluble tumor necrosis factor (TNF) receptor II (sTNF-RII), interleukin-1 receptor antagonist, and C-reactive protein.

Results

Symptoms were elevated at the end of treatment; greater than 60% of participants reported clinically significant problems with fatigue and sleep, and 25% reported elevated depressive symptoms. Women treated with chemotherapy endorsed higher levels of all symptoms and also had higher plasma levels of sTNF-RII than women who did not receive chemotherapy (all P < .05). Fatigue was positively associated with sTNF-RII, particularly in the chemotherapy-treated group (P < .05). Depressive symptoms and sleep problems were correlated with fatigue but not with inflammatory markers.

Conclusion

This study confirms high rates of behavioral symptoms in breast cancer survivors, particularly those treated with chemotherapy, and indicates a role for TNF-α signaling as a contributor to postchemotherapy fatigue. Results also suggest that fatigue, sleep disturbance, and depression may stem from distinct biologic processes in post-treatment survivors, with inflammatory signaling contributing relatively specifically to fatigue.
The evolution of nervous system patterning: insights from sea urchin development
Authors: Angerer Lynne M. , Yaguchi Shunsuke , Angerer Robert C. , Burke Robert D.
Published: August 2011

Recent studies of the sea urchin embryo have elucidated the mechanisms that localize and pattern its nervous system. These studies have revealed the presence of two overlapping regions of neurogenic potential at the beginning of embryogenesis, each of which becomes progressively restricted by separate, yet linked, signals, including Wnt and subsequently Nodal and BMP. These signals act to specify and localize the embryonic neural fields – the anterior neuroectoderm and the more posterior ciliary band neuroectoderm – during development. Here, we review these conserved nervous system patterning signals and consider how the relationships between them might have changed during deuterostome evolution.
A LIM-homeobox gene is required for differentiation of Wnt-expressing cells at the posterior end of the planarian body
Authors: Hayashi Tetsutaro , Motoishi Minako , Yazawa Shigenobu , Itomi Kazu , Tanegashima Chiharu , Nishimura Osamu , Agata Kiyokazu , Tarui Hiroshi
Published: August 2011

Planarians have high regenerative ability, which is dependent on pluripotent adult somatic stem cells called neoblasts. Recently, canonical Wnt/β-catenin signaling was shown to be required for posterior specification, and Hedgehog signaling was shown to control anterior-posterior polarity via activation of the Djwnt1/P-1 gene at the posterior end of planarians. Thus, various signaling molecules play an important role in planarian stem cell regulation. However, the molecular mechanisms directly involved in stem cell differentiation have remained unclear. Here, we demonstrate that one of the planarian LIM-homeobox genes, Djislet, is required for the differentiation of Djwnt1/P-1-expressing cells from stem cells at the posterior end. RNA interference (RNAi)-treated planarians of Djislet [Djislet(RNAi)] show a tail-less phenotype. Thus, we speculated that Djislet might be involved in activation of the Wnt signaling pathway in the posterior blastema. When we carefully examined the expression pattern of Djwnt1/P-1 by quantitative real-time PCR during posterior regeneration, we found two phases of Djwnt1/P-1 expression: the first phase was detected in the differentiated cells in the old tissue in the early stage of regeneration and then a second phase was observed in the cells derived from stem cells in the posterior blastema. Interestingly, Djislet is expressed in stem cell-derived DjPiwiA- and Djwnt1/P-1-expressing cells, and Djislet(RNAi) only perturbed the second phase. Thus, we propose that Djislet might act to trigger the differentiation of cells expressing Djwnt1/P-1 from stem cells.
Ancestral functions of Delta/Notch signaling in the formation of body and leg segments in the cricketGryllus bimaculatus
Authors: Mito Taro , Shinmyo Yohei , Kurita Kazuki , Nakamura Taro , Ohuchi Hideyo , Noji Sumihare
Published: August 2011

Delta/Notch signaling controls a wide spectrum of developmental processes, including body and leg segmentation in arthropods. The various functions of Delta/Notch signaling vary among species. For instance, in Cupiennius spiders, Delta/Notch signaling is essential for body and leg segmentation, whereas in Drosophila fruit flies it is involved in leg segmentation but not body segmentation. Therefore, to gain further insight into the functional evolution of Delta/Notch signaling in arthropod body and leg segmentation, we analyzed the function of the Delta (Gb′Delta) and Notch (Gb′Notch) genes in the hemimetabolous, intermediate-germ cricket Gryllus bimaculatus. We found that Gb′Delta and Gb′Notch were expressed in developing legs, and that RNAi silencing of Gb′Notch resulted in a marked reduction in leg length with a loss of joints. Our results suggest that the role of Notch signaling in leg segmentation is conserved in hemimetabolous insects. Furthermore, we found that Gb′Delta was expressed transiently in the posterior growth zone of the germband and in segmental stripes earlier than the appearance of wingless segmental stripes, whereas Gb′Notch was uniformly expressed in early germbands. RNAi knockdown of Gb′Delta or Gb′Notch expression resulted in malformation in body segments and a loss of posterior segments, the latter probably due to a defect in posterior growth. Therefore, in the cricket, Delta/Notch signaling might be required for proper morphogenesis of body segments and posterior elongation, but not for specification of segment boundaries.
VEGF signalling controls GnRH neuron survival via NRP1 independently of KDR and blood vessels
Authors: Cariboni Anna , Davidson Kathryn , Dozio Elena , Memi Fani , Schwarz Quenten , Stossi Fabio , Parnavelas John G. , Ruhrberg Christiana
Published: August 2011

Gonadotropin-releasing hormone (GnRH) neurons are neuroendocrine cells that are born in the nasal placode during embryonic development and migrate through the nose and forebrain to the hypothalamus, where they regulate reproduction. Many molecular pathways that guide their migration have been identified, but little is known about the factors that control the survival of the migrating GnRH neurons as they negotiate different environments. We previously reported that the class 3 semaphorin SEMA3A signals through its neuropilin receptors, NRP1 and NRP2, to organise the axons that guide migrating GnRH neurons from their birthplace into the brain. By combining analysis of genetically altered mice with in vitro models, we show here that the alternative neuropilin ligand VEGF164 promotes the survival of migrating GnRH neurons by co-activating the ERK and AKT signalling pathways through NRP1. We also demonstrate that survival signalling relies on neuronal, but not endothelial, NRP1 expression and that it occurs independently of KDR, the main VEGF receptor in blood vessels. Therefore, VEGF164 provides survival signals directly to developing GnRH neurons, independently of its role in blood vessels. Finally, we show that the VEGF164-mediated neuronal survival and SEMA3A-mediated axon guidance cooperate to ensure that migrating GnRH neurons reach the brain. Thus, the loss of both neuropilin ligands leads to an almost complete failure to establish the GnRH neuron system.
Notch signaling: simplicity in design, versatility in function
Authors: Andersson Emma R. , Sandberg Rickard , Lendahl Urban
Published: August 2011

Notch signaling is evolutionarily conserved and operates in many cell types and at various stages during development. Notch signaling must therefore be able to generate appropriate signaling outputs in a variety of cellular contexts. This need for versatility in Notch signaling is in apparent contrast to the simple molecular design of the core pathway. Here, we review recent studies in nematodes, Drosophila and vertebrate systems that begin to shed light on how versatility in Notch signaling output is generated, how signal strength is modulated, and how cross-talk between the Notch pathway and other intracellular signaling systems, such as the Wnt, hypoxia and BMP pathways, contributes to signaling diversity.
Pax7-expressing satellite cells are indispensable for adult skeletal muscle regeneration
Authors: Sambasivan Ramkumar , Yao Roseline , Kissenpfennig Adrien , Van Wittenberghe Laetitia , Paldi Andràs , Gayraud-Morel Barbara , Guenou Hind , Malissen Bernard , Tajbakhsh Shahragim , Galy Anne
Published: August 2011

Distinct cell populations with regenerative capacity have been reported to contribute to myofibres after skeletal muscle injury, including non-satellite cells as well as myogenic satellite cells. However, the relative contribution of these distinct cell types to skeletal muscle repair and homeostasis and the identity of adult muscle stem cells remain unknown. We generated a model for the conditional depletion of satellite cells by expressing a human diphtheria toxin receptor under control of the murine Pax7 locus. Intramuscular injection of diphtheria toxin during muscle homeostasis, or combined with muscle injury caused by myotoxins or exercise, led to a marked loss of muscle tissue and failure to regenerate skeletal muscle. Moreover, the muscle tissue became infiltrated by inflammatory cells and adipocytes. This localised loss of satellite cells was not compensated for endogenously by other cell types, but muscle regeneration was rescued after transplantation of adult Pax7+ satellite cells alone. These findings indicate that other cell types with regenerative potential depend on the presence of the satellite cell population, and these observations have important implications for myopathic conditions and stem cell-based therapeutic approaches.
Effective fiber hypertrophy in satellite cell-depleted skeletal muscle
Authors: McCarthy John J. , Mula Jyothi , Miyazaki Mitsunori , Erfani Rod , Garrison Kelcye , Farooqui Amreen B. , Srikuea Ratchakrit , Lawson Benjamin A. , Grimes Barry , Keller Charles , Van Zant Gary , Campbell Kenneth S. , Esser Karyn A. , Dupont-Versteegden Esther E. , Peterson Charlotte A.
Published: August 2011

An important unresolved question in skeletal muscle plasticity is whether satellite cells are necessary for muscle fiber hypertrophy. To address this issue, a novel mouse strain (Pax7-DTA) was created which enabled the conditional ablation of >90% of satellite cells in mature skeletal muscle following tamoxifen administration. To test the hypothesis that satellite cells are necessary for skeletal muscle hypertrophy, the plantaris muscle of adult Pax7-DTA mice was subjected to mechanical overload by surgical removal of the synergist muscle. Following two weeks of overload, satellite cell-depleted muscle showed the same increases in muscle mass (approximately twofold) and fiber cross-sectional area with hypertrophy as observed in the vehicle-treated group. The typical increase in myonuclei with hypertrophy was absent in satellite cell-depleted fibers, resulting in expansion of the myonuclear domain. Consistent with lack of nuclear addition to enlarged fibers, long-term BrdU labeling showed a significant reduction in the number of BrdU-positive myonuclei in satellite cell-depleted muscle compared with vehicle-treated muscle. Single fiber functional analyses showed no difference in specific force, Ca2+ sensitivity, rate of cross-bridge cycling and cooperativity between hypertrophied fibers from vehicle and tamoxifen-treated groups. Although a small component of the hypertrophic response, both fiber hyperplasia and regeneration were significantly blunted following satellite cell depletion, indicating a distinct requirement for satellite cells during these processes. These results provide convincing evidence that skeletal muscle fibers are capable of mounting a robust hypertrophic response to mechanical overload that is not dependent on satellite cells.
Pre-Electrospray Ionisation Manifold Methylation and Post-Electrospray Ionisation Manifold Cleavage/Ion Cluster Formation Observed during Electrospray Ionisation of Chloramphenicol in Solutions of Methanol and Acetonitrile for Liquid Chromatography-Mass Spectrometry Employing a Commercial Quadrupole Ion Trap Mass Analyser
Authors: Sichilongo Kwenga F. , Famuyiwa Samson O. , Kibechu Rose
Published: August 2011

We have observed unusual mass spectra of chloramphenicol (CAP) in solutions of methanol or acetonitrile showing intense ions at m/z 297, m/z 311, m/z 325 and m/z 339. The ions observed were different from those which are traditionally observed in the full scan electrospray ionization (ESI) mass spectra of CAP with ions of m/z 321, m/z 323 and m/z 325. We have evidence to show that this process starts with off-line methylation of CAP in solutions of methanol or acetonitrile to give m/z 339. Investigations using nuclear magnetic resonance spectroscopy showed that there is a methylene group somewhere within the CAP molecule but not attached to any of the carbon atoms when the CAP is dissolved in methanol or acetonitrile before infusion into the mass spectrometer. The possible locations of attachment were speculated to be the electronegative atoms apart from the chlorine atoms due to valence considerations. The methylene group is attached to the nitrogen atom and forms a bond as observed in the MS/MS spectra of m/z 297, m/z 311, m/z 325 and m/z 339 which give m/z 183 as the base peak in all cases. Further experiments showed that there is cleavage of the methylated CAP molecule followed by cluster ion formation involving addition of methylene groups to the CAP fragment with m/z 183 to produce ions of m/z including 297, 311, 325 and 339. This process occurs in the mass spectrometer in the region housing the tube lens and is triggered when the ions are accelerated through this region by application of a negative tube lens offset voltage. This region affords collision of the charged droplets with a collision gas in this case nitrogen to strip the droplets of their solvent molecules. Experiments to follow the intensities of m/z 183, m/z 311, m/z 321, m/z 323, m/z 325 and m/z 339 as the tube lens offset voltage was varied were done in which the intensities of m/z 311, m/z 325 and m/z 339 were observed to be at their peak when the tube lens offset voltage was set at −40 V. When the tube lens offset voltage is swung to +40V, thus decelerating the ions through the capillary skimmer region via the tube lens, the traditionally observed spectra with m/z 321, m/z 323 and m/z 325 were observed.
Differentiation of Diasteromeric α-Sulfanyl-β-Amino Acid Derivatives by Electrospray Ionisation Tandem Mass Spectrometry
Authors: Ramanjaneyulu Gundimeda S. , Darshan Davalagar Vijay , Mahendar Koosam , Kantam Mannepalli Lakshmi , Prabhakar Sripadi
Published: August 2011

A set of diastereomeric α-sulfanyl-β-amino acid derivatives, which are important building blocks for pharmaceuticals with potent biological activity, are studied by electrospray ionisation tandem mass spectrometry. The collision-induced dissociation (CID) spectra of [M + H]+, [M + NH4]+, [M + Na]+ and [M + Li]+ of the diastereomers were studied, among them the CID of [M + Na]+ and [M + Li]+ showed consistent differences in the relative abundance of characteristic ions that enabled distinction of the anti isomers from syn isomers. The decomposition pathways for the diagnostic ions were arrived at based on high-resolution mass spectrometry data, multiple mass spectrometry data, deuterium labelling experiments and the mass shift in accordance with the substituents located at different places. Loss of (R1–C6H4–CH=NH) and (Cat–NH–SO2R2) from [M + Cat]+, where Cat = Na and Li and the product ions, as a results of McLafferty rearrangement involving either the >S=O or >C=O groups, were found to be diagnostic. The McLafferty rearrangement product ions involving the >S=O group were more abundant in syn isomers while those involving the >C=O group were more abundant in anti isomers. The selectivity observed in the decomposition of [M + Li]+ ions was found to be similar to that of [M + Na]+ ions but, in a few cases, the differences are marginal in the decomposition of [M + Li]+ ions.
Identification of Indole Alkaloids in Nauclea Officinalis Using High-Performance Liquid Chromatography Coupled with Ion Trap and Time-of-Flight Mass Spectrometry
Authors: Li Qin , Zhang Yufeng , Wu Bin , Qu Haibin
Published: August 2011

Indole alkaloids from Nauclea officinalis (Pierra ex Pitard) Merr are prospective agents for inflammation-related diseases. To speed up the process of discovering such bioactive compounds from natural origins, a mass spectrometry-based method was developed to screen N. officinalis for the presence of indole alkaloids. First, representative alkaloids were purified from herbs and analyzed using an ion trap (IT) mass spectrometer. Multi-stage mass spectra (MS n)were utilized to establish the characteristic fragmentation pathways of indole alkaloids. It was shown that their fragmentation behaviors were correlated with the degree of unsaturation on ring-D of such alkaloids: if there is a double bond between C-3 and C-14, no fragments of ring cleavage are observed; otherwise, a fragment ion after reverse Diels–Alder cleavage of ring-D is observed as the base peak in their tandem mass spectrometry data. Then, herbal extracts of N. officinalis were analyzed using a combination of high-performance liquid chromatography (HPLC)/IT and HPLC/time-of-flight (ToF) systems. The structures of suspected alkaloids were deduced based on the accurate mass information from ToF and MS n from IT. Finally, a total of 10 indole and one indolizidine alkaloids were identified or tentatively characterized in extracts of N. officinalis. This work has demonstrated that the combination of MS n and ToF MS can be used for rapid identification of monoterpenoid indole alkaloids in N. officinalis.
Rapid Detection and Identification of Impurities in Ten 2-Naphthalenamines Using an Atmospheric Pressure Solids Analysis Probe in Conjunction with Ion Mobility Mass Spectrometry
Authors: Pan Hefeng , Lundin Göran
Published: August 2011

The atmospheric pressure solids analysis probe (ASAP), in conjunction with ion mobility time-of-flight mass spectrometry (IM-ToF-MS), has been applied to the impurity profiling study of ten 2-naphthalenamines. The impurity profiles achieved by ASAP-IM-MS were compared with those obtained by liquid chromatography-electrospray ionisation–mass spectrometry (LC-ESI-MS). All the impurities at the level of 0.1 area % and above, except for one, detected by LC-ESI-MS, were also found by ASAP-IMS analyses. In addition, one non-polar compound was detected by ASAP-IM-MS alone. The IM-MS plot of ion drift time versus m/z values offered sufficient separation between the impurities with different m/z. Therefore, instead of LC as a separation tool, IM-MS is able to provide fingerprint profiling for the ten samples analysed. The time of each analysis has been reduced from 25 min by LC-MS to less than 3 min by ASAP-IM-MS. When collision energy was applied for the selected precursor ion in the transfer T-wave, a clean MS/MS spectrum was obtained for structural elucidation of unknown impurities. The hyphenation of ASAP and IM-MS techniques represents a highly efficient approach for rapid detection and identification of impurities generated in complex reactions involved in pharmaceutical development.
Delapril and Manidipine Measurements by Liquid Chromatography—Tandem Mass Spectrometry in a Pharmaceutical Formulation
Authors: Todeschini Vítor , da Silva Sangoi Maximiliano , Volpato Nadia Maria
Published: August 2011

A simple, specific, fast and sensitive liquid chromatography–tandem mass spectrometry (LC-MS/MS) method for the simultaneous analysis of delapril (DEL) and manidipine (MAN) from their combination formulation was developed and validated using fesoterodine as the internal standard (IS). The LC-MS/MS method was carried out on a Luna C8 column (50 × 3.0 mm i.d., 3 μm) with a mobile phase consistingof methanol and 10 mmol L−1 ammonium acetate (90:0, v/v), run at a flow rate of 0.25 mL min−1. The mass spectrometry method was performed employing positive electrospray ionization operating in multiple reaction monitoring mode, monitoring the transitions of m/z 453.1 → 234.1 for DEL, m/z 611.1 → 167.0 for MAN and m/z 412.2 → 223.0 for IS. The total analysis time was 3 min and the method was linear in the concentration range of 6–1080 ng mL−1 and 2–360 ng mL−1 for DEL and MAN, respectively. Parameters investigated for the method validation, such as the specificity, linearity, precision, accuracy and robustness, gave results within the acceptable range. Moreover, the proposed method was successfully applied for the simultaneous determination of DEL and MAN and the results were compared to validated liquid chromatography and capillary electrophoresis methods showing non-significant differences ( P = 0.9).
Electron Ionisation Mass Spectral Study of Oxo- and Thio Derivatives of Minor Tobacco Alkaloids
Authors: Jasiewicz Beata , Wojciechowska-Nowak Marzena , Boczoń Władysław , Wyrzykiewicz Elzbieta
Published: August 2011

The electron ionisation mass spectra (EI-MS) of oxo- and thio derivatives of minor tobacco alkaloids and structurally similar piperidine alkaloids, i.e. thiocotinine (1), 2′-oxo- N-methylanabasine (2), 2′-thio- N-methylanabasine (3), 2′-oxoanabasamine (4) and 2′-thioanabasamine (5) are discussed and general fragmentation routes of their molecular cations are proposed. Comparison of the data obtained for1with the EI-MS data of metameric metabolites of nicotine: 3′-hydroxycotinine, (A) and 5′-hydroxycotinine, (B) allows a differentiation between these metamers. The data will be useful for the identification of metabolites of alkaloids of these types in biological matrices.
Study of Metal Ion Labeling of the Conformational and Charge States of Lysozyme by Ion Mobility Mass Spectrometry
Authors: Angel Laurence A.
Published: August 2011

The efficiency of Zn2+, Cu2+, Ni2+, Co2+, Fe2+ or Mn2+ labeling of the conformational and charge states of lysozyme was studied in H2O solvent at pH 2.5–6.8. Labeling of lysozyme was conducted with 50 M, 100 M and 500 M excess of the metal ion, resulting in the number of metal ions attached to lysozyme increasing two-fold over this range. At pH 6.2–6.8, Zn2+, Cu2+, Ni2+, Co2+ and Mn2+ labeled the highly folded 7+ conformer and the 8+ and 9+ partially unfolded conformers of lysozyme with the same number of metal ion tags, with only Fe2+ exhibiting no labeling. Lysozyme conserved its charge after metal ion labeling which shows at each charge state the divalent metal ion is replacing two protons. As the pH is lowered to 4.7–5.0 and 2.5–2.9, the labeling of lysozyme by Zn2+, Cu2+, Ni2+, Co2+ or Mn2+ decreased in efficiency due to increased competition from protons for the aspartate and glutamate binding sites. The metal ions preferentially labeled the highly folded 7+ and partially unfolded 8+ conformers, but labeling decreased as the charge of lysozyme increased. In contrast to the other metal ions, Fe2+ exhibited labeling of lysozyme only at the lowest pH of 2.8. At higher pH, the oxidation of Fe2+ and formation of hydroxy-bridged complexes probably make the Fe2+ unreactive towards lysozyme.
Blunt injury of the innominate artery and left innominate vein
Authors: Davidović Lazar , Ilić Nikola , Cvetković Slobodan , Koncar Igor , Čolić Momčilo , Vjestica Milica
Published: August 2011

Injuries to the branches of the aortic arch are rare and may be caused by blunt, penetrating, blast or iatrogenic trauma. Innominate vascular injury is a rare entity, particularly in blunt trauma. It is estimated that 71% of patients with innominate injuries die before arrival at the hospital. We report here a successfully managed case of a combined blunt trauma of the innominate artery and transection of the left innominate vein after blunt injury to the chest.
Gram-negative groin sepsis treated with covered stents and systemic antibiotics
Authors: Leon Luis R , Thai Janice , Pacanowski John P
Published: August 2011

Prosthetic graft infections are hazardous conditions. Those due to Gram-negative bacteria are particularly serious. When Gram-negative microorganisms are present, entire graft excision is recommended, with revascularization if needed, preferably with autogenous tissues or with prosthetic grafts via non-infected planes if autogenous options are not available. We herein report the case of a diabetic man with critical limb ischemia, who after lower-extremity revascularization with a prosthetic graft, developed an early graft infection due to Gram-negative and fungal organisms, and who was successfully treated with a covered stent placed across grossly infected tissues. A discussion on the pertinent literature is also offered.
Resection and primary repair of an inferior vena cava aneurysm in a 13-year-old male
Authors: Weber Cynthia , Jones Keith , Milner Ross
Published: August 2011

We present a case of a 13-year-old boy who presented with a three-day history of left lower extremity swelling and a deep venous thrombosis. On further work-up he was discovered to have a large aneurysm of the inferior vena cava. After extensive discussion with his family, he underwent resection and primary repair of the inferior vena cava without complication. At a six-month follow up appointment, he was doing well with no recurrent aneurysmal degeneration on computed tomography scan imaging.
Preoperative cardiac assessment in patients undergoing major vascular surgery
Authors: Troisi Nicola , Pulli Raffaele , Dorigo Walter , Lo Sapio Patrizia , Pratesi Carlo
Published: August 2011

The aim of this study was to evaluate the effectiveness of a preoperative standardized cardiac assessment in patients undergoing major vascular surgery. From January 2005 to December 2006, 1446 elective interventions for major vascular diseases (carotid stenosis, CS; abdominal aortic aneurysm, AAA; peripheral arterial obstructive disease, PAOD) were performed; 1090 out of these patients underwent preoperative diagnostic assessment on an outpatient basis. Thirty-day results in terms of cardiac mortality and morbidity rates were recorded. Patients suffered from a CS in 578 cases (53%), an AAA in 303 cases (27.8%) and a PAOD in 209 cases (19.2%). Four hundred thirty-two patients (39.6%) underwent further evaluation of cardiac functional capacity with non-invasive stress testing. Sixteen patients were successfully treated prior to vascular surgery. Thirty-day cardiac mortality and morbidity rates were 0.2% and 3.9%, respectively. A positive preoperative non-invasive stress testing did not affect 30-day cardiac outcomes. In conclusion, the use of an accurate preoperative cardiac assessment allowed us to obtain satisfactory perioperative results in patients undergoing major vascular surgery. Routine preoperative evaluation with non-invasive stress testing did not seem to improve perioperative cardiac results.
Reconstructive surgery for chronic lymphedema: a viable option, but
Authors: Lee B B , Laredo J , Neville R
Published: August 2011

The aim of the paper is to assess the efficacy of reconstructive lymphatic surgery in the treatment of chronic lymphedema via retrospective analysis. Lymphovenous anastomotic surgery (LVAS) or free lymph node transplant surgery (FLTS) was performed on 32 patients who failed to respond to complex decongestive therapy (CDT) alone for a minimum of a one-year period. In LVAS, three patients with good compliance among 19 were able to maintain initial improvement through the four-year follow-up period. All three had secondary lymphedema in clinical stage II. In FLTS, among 13 patients, three compliant patients with the secondary lymphedema in clinical stage II kept initial improvement through the four-year follow-up. In conclusion, reconstructive lymphatic surgery (LVAS and FLTS) appears to be more effective in secondary lymphedema versus primary lymphedema when performed in the early stages. Patient compliance to maintain CDT postoperatively remains the most critical factor in maintaining durable long-term results. FLTS seems to have an additional risk involved to the donor lymph node harvest and a limited role compared to LVAS. Further extended study on FLTS is required to demonstrate its efficacy compared with LVAS.
Mesenchymal stem cell-based tissue engineering of small-diameter blood vessels
Authors: Dong Jian-De , Huang Jin-Hong , Gao Feng , Zhu Zhao-Hui , Zhang Jian
Published: August 2011

The aim of the study was to construct small-diameter vascular grafts using canine mesenchymal stem cells (cMSCs) and a pulsatile flow bioreactor. cMSCs were isolated from canine bone marrow and expanded ex vivo. cMSCs were then seeded onto the luminal surface of decellularized arterial matrices, which were further cultured in a pulsatile flow bioreactor for four days. Immunohistochemical staining and scanning electron microscopy was performed to characterize the tissue-engineered blood vessels. cMSCs were successfully seeded onto the luminal surface of porcine decellularized matrices. After four-day culture in the pulsatile flow bioreactor, the cells were highly elongated and oriented to the flow direction. Immunohistochemistry demonstrated that the cells cultured under pulsatile flow expressed Von Willebrand factor, an endothelial cell marker. In conclusion, cMSCs seeded onto decellularized arterial matrices could differentiate into endothelial lineage after culturing in a pulsatile flow bioreactor, which provides a novel approach for tissue engineering of small-diameter blood vessels.
Why we need open simulation to train surgeons in an era of work-hour restrictions
Authors: Bath Jonathan , Lawrence Peter
Published: August 2011

Surgical training in the USA and Europe has undergone radical changes with respect to working patterns, culture and limitation on working hours in recent years. Many surgeons who trained prior to the Accreditation Council for Graduate Medical Education (ACGME) duty-hour restrictions have expressed concern that surgeons currently exiting from training may not have had the same operative experience as in the pre-ACGME era. These concerns are particularly relevant in vascular surgery with the prevalence of endovascular therapies reducing the exposure of trainees to more traditional open vascular operations. Simulation has been used in many non-medical fields for technical skill acquisition prior to real-life performance and in recent years has been identified as a useful tool in surgical training. This article highlights the growing need for open vascular simulation as exposure to complex open vascular operations diminishes. The culture of, ‘see one, do one, teach one’ is fast becoming replaced by ‘do many on a simulator, attain competency then perform under supervision in the operating room’. This will only be successfully achieved by the widespread incorporation of open vascular simulation into current vascular training programs if work hours remain limited and endovascular modalities continue to replace traditional open operations.
Structural and biochemical properties of Sept7, a unique septin required for filament formation
Authors: Zent Eldar , Vetter Ingrid , Wittinghofer Alfred
Published: August 2011

Septins constitute a family of conserved guanine nucleotide binding proteins found in a wide range of organisms from fungi to mammals. Members of the family share a canonical G-domain with N- and C-terminal extensions. G-domains assemble into hetero-oligomeric complexes which form non-polarised filaments or rings. Linear filaments are formed between the G-domains using either the guanine nucleotide binding site (G interface) or N- and C-terminal extensions (NC interface). Sept7 is a unique among the 13 human septins in that it occupies the ends of hexameric building blocks which assemble into non-polarised filaments. To gain insight into its particular properties we performed structural and biochemical studies on Sept7. We solved the crystal structure of a Sept7 dimer in the GDP-bound state. The structure and biochemistry of Sept7 provide new insights into the dynamics of the G interface and outline the differences in the properties of Sept7 compared to the members of group 2 septins.
Evidence that a septin diffusion barrier is dispensable for cytokinesis in budding yeast
Authors: Wloka Carsten , Nishihama Ryuichi , Onishi Masayuki , Oh Younghoon , Hanna Julia , Pringle John R. , Krauß Michael , Bi Erfei
Published: August 2011

Septins are essential for cytokinesis in Saccharomyces cerevisiae, but their precise roles remain elusive. Currently, it is thought that before cytokinesis, the hourglass-shaped septin structure at the mother-bud neck acts as a scaffold for assembly of the actomyosin ring (AMR) and other cytokinesis factors. At the onset of cytokinesis, the septin hourglass splits to form a double ring that sandwiches the AMR and may function as diffusion barriers to restrict diffusible cytokinesis factors to the division site. Here, we show that in cells lacking the septin Cdc10 or the septin-associated protein Bud4, the septins form a ring-like structure at the mother-bud neck that fails to re-arrange into a double ring early in cytokinesis. Strikingly, AMR assembly and constriction, the localization of membrane-trafficking and extracellular-matrix-remodeling factors, cytokinesis, and cell-wall-septum formation all occur efficiently in cdc10Δ and bud4Δ mutants. Thus, diffusion barriers formed by the septin double ring do not appear to be critical for S. cerevisiae cytokinesis. However, an AMR mutation and a septin mutation have synergistic effects on cytokinesis and the localization of cytokinesis proteins, suggesting that tethering to the AMR and a septin diffusion barrier may function redundantly to localize proteins to the division site.
Septin9 is involved in septin filament formation and cellular stability
Authors: Füchtbauer Annette , Lassen Louise B. , Jensen Astrid B. , Howard Jennifer , Quiroga Adán de Salas , Warming Søren , Sørensen Annette B. , Pedersen Finn S. , Füchtbauer Ernst-Martin
Published: August 2011

Septin9 (Sept9) is a member of the filament-forming septin family of structural proteins and is associated with a variety of cancers and with hereditary neuralgic amyotrophy. We have generated mice with constitutive and conditional Sept9 knockout alleles. Homozygous deletion of Sept9 results in embryonic lethality around day 10 of gestation whereas mice homozygous for the conditional allele develop normally. Here we report the consequences of homozygous loss of Sept9 in immortalized murine embryonic fibroblasts. Proliferation rate was not changed but cells without Sept9 had an altered morphology compared to normal cells, particularly under low serum stress. Abnormal, fragmented, and multiple nuclei were more frequent in cells without Sept9. Cell migration, as measured by gap-filling and filter-invasion assays, was impaired, but individual cells did not move less than wild-type cells. Sept9 knockout cells showed a reduced resistance to hypo-osmotic stress. Stress fiber and vinculin staining at focal adhesion points was less prominent. Long septin filaments stained for Sept7 disappeared. Instead, staining was found in short, often curved filaments and rings. Furthermore, Sept7 was no longer localized to the mitotic spindle. Together, these data reveal the importance of Sept9 for septin filament formation and general cell stability.
ARTS, the unusual septin: structural and functional aspects
Authors: Mandel-Gutfreund Yael , Kosti Idit , Larisch Sarit
Published: August 2011

The human Septin 4 gene (Sept4) encodes two major protein isoforms; Sept4_i1 (H5/PNUTL2) and Sept4_i2/ARTS. Septins have been traditionally studied for their role in cytokinesis and their filament-forming abilities, but subsequently have been implicated in diverse functions, including membrane dynamics, cytoskeletal reorganization, vesicle trafficking, and tumorigenesis. ARTS is localized at mitochondria and promotes programmed cell death (apoptosis). These features distinguish ARTS from any other known human septin family member. This review compares the structural and functional properties of ARTS with other septins. In addition, it describes how a combination of two distinct promoters, differential splicing, and intron retention leads to the generation of two different Sept4 variants with diverse biological activity.