bluuebunny/crossref_metadata_2025 huggingface dataset:
Posterior fossa arteriovenous malformations
Authors: Arnaout Omar M. , Gross Bradley A. , Eddleman Christopher S. , Bendok Bernard R. , Getch Christopher C. , Batjer H. Hunt
Published: May 2009

Arteriovenous malformations (AVMs) of the posterior fossa are complex neurovascular lesions that are less common than their supratentorial counterparts, accounting for < 15% of all AVMs. The majority of patients with these lesions present with intracranial hemorrhage, a factor that has been consistently shown to increase one's risk for subsequent bleeding. Studies have additionally shown a posterior fossa or deep AVM location to portend a more aggressive natural history. The authors reviewed the literature on posterior fossa AVMs, finding their annual rupture rates to be as high as 11.6%, an important factor that underscores the importance of aggressive treatment of lesions amenable to intervention as therapeutic options and results continue to improve.
Giant serpentine aneurysms
Authors: Christiano Lana D. , Gupta Gaurav , Prestigiacomo Charles J. , Gandhi Chirag D.
Published: May 2009

Segal and McLaurin first described giant serpentine aneurysms, based on their distinct angiographic features, in 1977. These lesions are ≥ 25 mm, partially thrombosed aneurysms with a patent, serpiginous vascular channel that courses through the aneurysm. There is a separate inflow and outflow of the aneurysm, of which the outflow channel supplies brain parenchyma in the territory of the parent vessel. Given the large size, unique neck, and dependent distal vessels, these aneurysms pose a technical challenge in treatment. Initial management has included surgical obliteration, but as endovascular techniques have evolved, treatment options too have expanded. In this review the authors attempt to summarize the existing body of literature on this rare entity and describe some of their institutional management strategies.
Radiosurgery for angiographically occult vascular malformations
Authors: Pham Martin , Gross Bradley A. , Bendok Bernard R. , Awad Issam A. , Batjer H. Hunt
Published: May 2009

The use of radiosurgery for angiographically occult vascular malformations (AOVMs) is a controversial treatment option for those that are surgically inaccessible or located in eloquent brain. To determine the efficacy of this treatment, the authors reviewed the literature reporting hemorrhage rates, seizure control, and radiation-induced morbidity. They found overall hemorrhage rates of 2–6.4%, overall postradiosurgery hemorrhage rates of 1.6–8%, and stratified postradiosurgery hemorrhage rates of 7.3–22.4% in the period immediately to 2 years after treatment; these latter rates declined to 0.8–5.2% > 2 years after treatment. Of 291 patients presenting with seizure across 16 studies, 89 (31%) attained a seizure-free status and 102 (35%) had a reduction in seizure frequency after radiosurgery. Overall radiation-induced morbidity ranged from 2.5 to 59%, with higher complication rates in patients with brainstem lesion locations. Researchers applying mean radiation doses of 15–16.2 Gy to the tumor margin saw both low radiationinduced complication rates (0–9.1%) and adequate hemorrhage control (0.8–5.2% > 2 years after treatment), whereas mean doses ≥ 16.5 Gy were associated with higher total radiation-induced morbidity rates (> 17%). Although the use of stereotactic radiosurgery remains controversial, patients with AOVMs located in surgically inaccessible areas of the brain may benefit from such treatment.
Cranial dural arteriovenous fistulas: modification of angiographic classification scales based on new natural history data
Authors: Zipfel Gregory J. , Shah Manish N. , Refai Daniel , Dacey Ralph G. , Derdeyn Colin P.
Published: May 2009

This article presents a modification to the existing classification scales of intracranial dural arteriovenous fistulas based on newly published research regarding the relationship of clinical symptoms and outcome. The 2 commonly used scales, the Borden-Shucart and Cognard scales, rely entirely on angiographic features for categorization. The most critical anatomical feature is the identification of cortical venous drainage (CVD; Borden-Shucart Types II and III and Cognard Types IIb, IIa + b, III, IV, and V), as this feature identifies lesions at high risk for future hemorrhage or ischemic neurological injury. Yet recent data has emerged indicating that within these high-risk groups, most of the risk for future injury is in the subgroup presenting with intracerebral hemorrhage or nonhemorrhagic neurological deficits. The authors have defined this subgroup as symptomatic CVD. Patients who present incidentally or with symptoms of pulsatile tinnitus or ophthalmological phenomena have a less aggressive clinical course. The authors have defined this subgroup as asymptomatic CVD. Based on recent data the annual rate of intracerebral hemorrhage is 7.4–7.6% for patients with symptomatic CVD compared with 1.4–1.5% for those with asymptomatic CVD. The addition of asymptomatic CVD or symptomatic CVD as modifiers to the Borden-Shucart and Cognard systems improves their accuracy for risk stratification of patients with high-grade dural arteriovenous fistulas.
Cerebral arteriovenous malformations. Part 1: cellular and molecular biology
Authors: Moftakhar Parham , Hauptman Jason S. , Malkasian Dennis , Martin Neil A.
Published: May 2009

Object

The scientific understanding of the nature of arteriovenous malformations (AVMs) in the brain is evolving. It is clear from current work that AVMs can undergo a variety of phenomena, including growth, remodeling, and/or regression—and the responsible processes are both molecular and physiological. A review of these complex processes is critical to directing future therapeutic approaches. The authors performed a comprehensive review of the literature to evaluate current information regarding the genetics, pathophysiology, and behavior of AVMs.

Methods

A comprehensive literature review was conducted using PubMed to reveal the molecular biology of AVMs as it relates to their complex growth and behavior patterns.

Results

Growth factors involved in AVMs include vascular endothelial growth factor, fibroblast growth factor, transforming growth factor β, angiopoietins, fibronectin, laminin, integrin, and matrix metalloproteinases.

Conclusions

Understanding the complicated molecular milieu of developing AVMs is essential for defining their natural history. Growth factors, extracellular matrix proteins, and other molecular markers will be the key to unlocking novel targeted drug treatments for these brain malformations.
Endovascular management of spinal dural arteriovenous fistulas
Authors: Sivakumar Walavan , Zada Gabriel , Yashar Parham , Giannotta Steven L. , Teitelbaum George , Larsen Donald W.
Published: May 2009

Object

Spinal dural arteriovenous fistulas (DAVFs) are the most common spinal vascular malformations and can be a significant cause of myelopathy, yet remain inefficiently diagnosed lesions. Over the last several decades, the treatment of spinal DAVFs has improved tremendously due to improvements in neuroimaging, microsurgical, and endovascular techniques. The aim of this paper was to review the existing literature regarding the clinical characteristics, classification, and endovascular management of spinal DAVFs.

Methods

A search of the PubMed database from the National Library of Medicine and reference lists of all relevant articles was conducted to identify all studies pertaining to spinal DAVFs, spinal dural fistulas, and spinal vascular malformations, with particular attention to endovascular management and outcomes.

Results

The ability to definitively treat spinal DAVFs using endovascular embolization has significantly improved over the last several decades. Overall rates of definitive embolization of spinal DAVFs have ranged between 25 and 100%, depending in part on the embolic agent used and the use of variable stiffness microcatheters. The majority of recent studies in which N-butyl cyanoacrylate or other liquid embolic agents were used have reported success rates of 70–90%. Surgical treatment remains the definitive option in cases of failed embolization, repeated recanalization, or lesions not amenable to embolization. Clinical outcomes have been comparable to surgical treatment when the fistula and draining vein remain persistently occluded. Improvements in gait and motor function are more likely following successful treatment, whereas micturition symptoms are less likely to improve.

Conclusions

Endovascular embolization is an increasingly effective therapy in the treatment of spinal DAVFs, and can be used as a definitive intervention in the majority of patients that undergo modern endovascular intervention. A multidisciplinary approach to the treatment of these lesions is required, as surgery is required for refractory cases or those not amenable to embolization. Newer embolic agents, such as Onyx, hold significant promise for future therapy, yet long-term follow-up studies are required.
Intracranial aneurysms presenting with mass effect over the anterior optic pathways: neurosurgical management and outcomes
Authors: de Oliveira Jean G. , Borba Luis A. B. , Rassi-Neto Aziz , de Moura Samuel M. , Sanchez-Júnior Santiago L. , Rassi Márcio S. , de Holanda Carlos Vanderlei M. , Giudicissi-Filho Miguel
Published: May 2009

Object

Intracranial aneurysms may grow closer to anterior optic pathways, causing mass effect over these anatomical structures, including visual deficit. The authors retrospectively reviewed a series of aneurysms in patients presenting with visual field deficit caused by mass effect, to analyze the aneurysm's characteristics, the neurosurgical management of these aneurysms, as well as their clinical, visual, and radiological outcomes.

Methods

The authors reviewed the medical charts, neuroimaging examination results, and surgical videos of 15 patients presenting with visual symptoms caused by an aneurysm's mass effect over the anterior optic pathways. These patients were treated at the Department of Neurosurgery, Center of Neurology and Neurosurgery Associates, Hospital Beneficência Portuguesa de São Paulo, Brazil. Statistical analysis was performed to identify the variables related to partial or total recovery of the visual symptoms.

Results

All patients underwent microsurgical clip placement and emptying of their aneurysms. After a mean follow-up of 38.5 months, the mean postoperative Glasgow Outcome Scale score was 4.33, and the visual outcomes were as follows: 1 patient (6.6%) unchanged, 7 (46.6%) improved, and 7 (46.6%) experienced complete recovery from visual deficits. The variables that influenced the visual outcomes were the size of the aneurysm (p = 0.039), duration of the visual symptoms (p = 0.002), aneurysm wall calcification (p = 0.010), and intraluminal thrombosis (p = 0.007). Postoperative examination using digital subtraction angiography showed complete aneurysm occlusion in 14 (93.3%) of the 15 patients.

Conclusions

Intracranial aneurysms causing mass effect over the anterior optic pathways usually present with complex features. The best treatment option must include not only the aneurysm occlusion but also relief of the mass effect. Microsurgical clip placement with reduction of aneurysmal mass effect achieved improvement in visual ability or recovery from visual impairment, as well as total aneurysm occlusion, in 93.3% of the study group. Therefore, this option is well supported as the first choice of treatment for intracranial aneurysms presenting with mass effect over the anterior visual pathways.
The evolution of cerebral revascularization surgery
Authors: Hayden Melanie G. , Lee Marco , Guzman Raphael , Steinberg Gary K.
Published: May 2009

Among the relatively few surgeons to be awarded the Nobel Prize was Alexis Carrel, a French surgeon and pioneer in revascularization surgery at the turn of the 20th century. The authors trace the humble beginnings of cerebral revascularization surgery through to the major developments that helped shape the modern practice of cerebral bypass surgery. They discuss the cornerstone studies in the development of this technique, including the Extracranial/Intracranial Bypass Study initiated in 1977. Recent innovations, including modern techniques to monitor cerebral blood flow, microanastomosis techniques, and ongoing trials that play an important role in the evolution of this field are also evaluated.
Frontal-to-temporal horn shunt as treatment for temporal horn entrapment
Authors: Hervey-Jumper Shawn L. , Ziewacz John E. , Heth Jason A. , Sullivan Stephen E.
Published: May 2009

In cases of temporal horn entrapment caused by primary malignant central nervous system tumors, the goal is to restore physiological flow of cerebrospinal fluid (CSF) while preventing the spread of malignant tumor cells to distant sites. This goal is usually accomplished by placement of a traditional ventriculoperitoneal, ventriculopleural, or ventriculoatrial shunt. In this study, the authors describe a novel treatment approach using placement of a frontal-to-temporal horn shunt as an alternative to distal CSF diversion. Stereotactic surgery was used for placement of frontal-to-temporal horn shunts in 3 patients who presented with focal compressive symptoms caused by temporal horn dilation. Serial imaging studies confirmed temporal horn decompression with symptom resolution after a maximum of 20 months of follow-up (minimum 2 months in 1 patient who died of tumor progression). The authors believe this simple technique may be considered for use in all patients with neurological symptoms resulting from temporal horn dilation caused by malignant central nervous system neoplasms in which seeding of distant sites by CSF diversion is a concern.
Intraventricular cerebral cavernomas: a series of 12 patients and review of the literature
Authors: Kivelev Juri , Niemelä Mika , Kivisaari Riku , Hernesniemi Juha
Published: May 2009

Object

Intraventricular cavernomas (IVCs) occur in only 2–10% of patients with cerebral cavernomas. Reports concerning IVC are scarce and are limited mostly to sporadic case reports. In this paper, the authors present a series of 12 patients with IVCs that were treated at a single neurosurgical department. In addition, the authors reviewed the literature.

Methods

All clinical data were analyzed retrospectively. Follow-up questionnaires were sent to all patients. Outcome was assessed using the Glasgow Outcome Scale. The authors also conducted a PubMed search and found 77 cases of IVC.

Results

The patients' median age was 47 years, and the male/female ratio was 2:1. A cavernoma occurred in the lateral ventricle in 6 patients, in another 5 it was in the fourth ventricle, and 1 had a lesion in the third ventricle. Almost all patients presented with acute headache on admission and in more than half, the symptoms were related to cavernoma bleeding. In total, 8 rebleedings occurred in 5 patients during a median of 0.4 years. Three patients with a cavernoma of the fourth ventricle presented with a cranial nerve deficit. In 8 cases, a cavernoma was surgically treated an average of 1.3 years after the diagnosis. Only 1 patient underwent surgery in the acute phase after a major intraventricular/intracerebral hemorrhage. The median follow-up time was 2 years. No patient was lost to follow-up, and no patient died. In total, on follow-up 9 patients improved and 3 had a persistent neurological deficit, of which 2 existed before surgery.

Conclusions

In the present series, the IVCs had a high tendency for rehemorrhage. Surgery is advocated when hemorrhages are frequent, and the mass effect causes progressive neurological deficits. Microsurgical removal of the IVC is safe, but in the fourth ventricle it can carry increased risk for cranial nerve deficits.
Comparing the risks of frameless stereotactic biopsy in eloquent and noneloquent regions of the brain: a retrospective review of 284 cases
Authors: Air Ellen L. , Leach James L. , Warnick Ronald E. , McPherson Christopher M.
Published: May 2009

Object

Frameless stereotactic biopsy has been shown in multiple studies to be a safe and effective tool for the diagnosis of brain lesions. However, no study has directly evaluated its safety in lesions located in eloquent regions in comparison with noneloquent locations. In this study, the authors determine whether an increased risk of neurological decline is associated with biopsy of lesions in eloquent regions of the brain.

Methods

Medical records, including imaging studies, were reviewed for 284 cases in which frameless stereotactic biopsy procedures were performed by 19 neurosurgeons at 7 institutions between January 2000 and December 2006. Lesion location was classified as eloquent or noneloquent in each patient. The incidence of neurological decline was calculated for each group.

Results

During the study period, 160 of the 284 biopsies predominately involved eloquent regions of the brain. In evaluation of the complication rate with respect to biopsy site, neurological decline occurred in 9 (5.6%) of 160 biopsies in eloquent brain areas and 10 (8.1%) of 124 biopsies in noneloquent regions; this difference was not statistically significant (p = 0.416). A higher number of needle passes was associated with the presence of a postoperative hemorrhage at the biopsy site, although not with a change in the result of neurological examination.

Conclusions

Frameless stereotactic biopsy of lesions located in eloquent brain regions is as safe and effective as biopsy of lesions in noneloquent regions. Therefore, with careful planning, frameless stereotactic biopsy remains a valuable and safe tool for diagnosis of brain lesions, independent of lesion location.
Extended transsphenoidal approach for pituitary adenomas invading the anterior cranial base, cavernous sinus, and clivus: a single-center experience with 126 consecutive cases
Authors: Zhao Bing , Wei Yu-Kui , Li Gui-Lin , Li Yong-Ning , Yao Yong , Kang Jun , Ma Wen-Bin , Yang Yi , Wang Ren-Zhi
Published: May 2009

Object

The standard transsphenoidal approach has been successfully used to resect most pituitary adenomas. However, as a result of the limited exposure provided by this procedure, complete surgical removal of pituitary adenomas with parasellar or retrosellar extension remains problematic. By additional bone removal of the cranial base, the extended transsphenoidal approach provides better exposure to the parasellar and clival region compared with the standard approach. The authors describe their surgical experience with the extended transsphenoidal approach to remove pituitary adenomas invading the anterior cranial base, cavernous sinus (CS), and clivus.

Methods

Retrospective analysis was performed in 126 patients with pituitary adenomas that were surgically treated via the extended transsphenoidal approach between September 1999 and March 2008. There were 55 male and 71 female patients with a mean age of 43.4 years (range 12–75 years). There were 82 cases of macroadenoma and 44 cases of giant adenoma.

Results

Gross-total resection was achieved in 78 patients (61.9%), subtotal resection in 43 (34.1%), and partial resection in 5 (4%). Postoperative complications included transient cerebrospinal rhinorrhea (7 cases), incomplete cranial nerve palsy (5), panhypopituitarism (5), internal carotid artery injury (2), monocular blindness (2), permanent diabetes insipidus (1), and perforation of the nasal septum (2). No intraoperative or postoperative death was observed.

Conclusions

The extended transsphenoidal approach provides excellent exposure to pituitary adenomas invading the anterior cranial base, CS, and clivus. This approach enhances the degree of tumor resection and keeps postoperative complications relatively low. However, radical resection of tumors that are firm, highly invasive to the CS, or invading multidirectionally remains a big challenge. This procedure not only allows better visualization of the tumor and the neurovascular structures but also provides significant working space under the microscope, which facilitates intraoperative manipulation. Preoperative imaging studies and new techniques such as the neuronavigation system and the endoscope improve the efficacy and safety of tumor resection.
Global chloroplast phylogeny and biogeography of bracken (Pteridium; Dennstaedtiaceae)
Authors: Der Joshua P. , Thomson John A. , Stratford Jeran K. , Wolf Paul G.
Published: May 2009

Bracken ferns (genus Pteridium) represent an ancient species complex with a natural worldwide distribution. Pteridium has historically been treated as comprising a single species, but recent treatments have recognized several related species. Phenotypic plasticity, geographically structured morphological variation, and geographically biased sampling have all contributed to taxonomic confusion in the genus. We sampled bracken specimens worldwide and used variable regions of the chloroplast genome to investigate phylogeography and reticulate evolution within the genus. Our results distinguish two major clades within Pteridium, a primarily northern hemisphere Laurasian/African clade, which includes all taxa currently assigned to P. aquilinum, and a primarily southern hemisphere Austral/South American clade, which includes P. esculentum and P. arachnoideum. All European accessions of P. aquilinum subsp. aquilinum appear in a monophyletic group and are nested within a clade containing the African P. aquilinum taxa (P. aquilinum subsp. capense and P. aquilinum subsp. centrali‐africanum). Our results allow us to hypothesize the maternal progenitors of two allotetraploid bracken species, P. caudatum and P. semihastatum. We also discuss the biogeography of bracken in the context of the chloroplast phylogeny. Our study is one of the first to take a worldwide perspective in addressing variation in a broadly distributed species complex.
Early Mobility and Walking Program for Patients in Intensive Care Units: Creating a Standard of Care
Authors: Perme Christiane , Chandrashekar Rohini
Published: May 2009

New technologies in critical care and mechanical ventilation have led to long-term survival of critically ill patients. An early mobility and walking program was developed to provide guidelines for early mobility that would assist clinicians working in intensive care units, especially clinicians working with patients who are receiving mechanical ventilation. Prolonged stays in the intensive care unit and mechanical ventilation are associated with functional decline and increased morbidity, mortality, cost of care, and length of hospital stay. Implementation of an early mobility and walking program could have a beneficial effect on all of these factors. The program encompasses progressive mobilization and walking, with the progression based on a patient’s functional capability and ability to tolerate the prescribed activity. The program is divided into 4 phases. Each phase includes guidelines on positioning, therapeutic exercises, transfers, walking reeducation, and duration and frequency of mobility sessions. Additionally, the criteria for progressing to the next phase are provided. Use of this program demands a collaborative effort among members of the multidisciplinary team in order to coordinate care for and provide safe mobilization of patients in the intensive care unit.
Nurses’ Perceptions of End-of-Life Care After Multiple Interventions for Improvement
Authors: Hansen Lissi , Goodell Teresa T. , DeHaven Josi , Smith MaryDenise
Published: May 2009

Background Nurses working in intensive care units may lack knowledge and skills in end-of-life care, find caring for dying patients and the patients’ families stressful, and lack support to provide this care.

Objectives To describe nurses’ perceptions of (1) knowledge and ability, (2) work environment, (3) support for staff, (4) support for patients and patients’ families, and (5) stress related to specific work situations in the context of end-of-life care before (phase 1) and after (phase 2) implementation of approaches to improve end-of-life care. The approaches were a nurse-developed bereavement program for patients’ families, use of a palliative medicine and comfort care team, preprinted orders for the withdrawal of life-sustaining treatment, hiring of a mental health clinical nurse specialist, and staff education in end-of-life care.

Methods Nurses in 4 intensive care units at a university medical center reported their perceptions of end-of-life care by using a 5-subscale tool consisting of 30 items scored on a 4-point Likert scale. The tool was completed by 91 nurses in phase 1 and 127 in phase 2.

Results Improvements in overall mean scores on the 5 sub-scales indicated that the approaches succeeded in improving nurses’ perceptions. In phase 2, most of the subscale overall mean scores were higher than a desired criterion (<2.0, good). Analysis of variance indicated that some improvements occurred over time differently in the units; other improvements occurred uniformly.

Conclusions Continued practice development is needed in end-of-life care issues.
Mechanical Inoculation of Plant Viruses
Authors: Hull Roger
Published: May 2009

This technique is for the mechanical inoculation of viruses to plants. It is used to diagnose a virus by its reactions in a variety of plant species, to test the infectivity of virus samples using local lesion hosts, and to propagate viruses. The virus preparation is rubbed onto the surface of the leaf in such a way as to break the surface cells without causing too much mechanical damage. The preparation of the virus sample, its application to the leaf, and the care of the plants before and after inoculation are described. Curr. Protoc. Microbiol. 13:16B.6.1‐16B.6.4. © 2009 by John Wiley & Sons, Inc.
Periodic noise analysis of electric circuits: Artifacts, singularities and a numerical method
Authors: Brambilla Angelo , Gruosso Giambattista , Redaelli Massimo , Storti Gajani Giancarlo
Published: May 2009

In this paper it is shown that a numerical method largely adopted for the simulation of noise in autonomous circuits is affected by singularities that manifest when the frequency at which the noise analysis is carried out approaches a harmonic of the autonomous circuit. The resulting noise power spectral density (PSD) is thus characterized by spurious spikes. The presence of these singularities is for the first time justified from an analytical standpoint and their effects are shown by simulating some oscillators, employed as benchmarks. Furthermore, the presented approach justifies the 1/(fs−f)2shape of the PSD of noise at the output when thefsfrequency approaches theffundamental of a stable oscillator and the 1/|fs−f|3shape when the effects of flicker noise are manifest. Copyright © 2009 John Wiley & Sons, Ltd.
Simulation of nerve bundle activation by simultaneous multipoint extracellular stimulation with surface electrodes
Authors: Takahashi Hirokazu , Nakao Masayuki , Kaga Kimitaka
Published: May 2009

Neural prostheses for restoring lost functions can benefit from selective activation of nerves. We previously proposed a multipoint gating stimulation, which can selectively activate a desired portion of a nerve bundle, regardless of the density of the electrode. In this paper, we discuss the design of an electrode array and effective strategies to determine the stimulus parameters. Large electrodes were less affected by the relative location of the electrodes and the nodes of Ranvier, suggesting that a rectangular electrode, whose long side along a nerve bundle is longer than the internodal distance (i.e., on the order of 1 mm), would be more effective than a disk electrode. We were able to estimate an appropriate current at each electrode on the basis of a blocking threshold, above which no spike propagation was permitted. For lateral gating stimulation, the gate current should be set above the threshold, while for depthwise gating stimulation, the gate current should be set below the threshold. The spatial resolutions of lateral and depthwise gating stimulation were theoretically estimated to be at least 50 μm when the grid spacing of the array was 1.2 mm. © 2009 Wiley Periodicals, Inc. Electron Comm Jpn, 92(6): 31–40, 2009; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/ecj.10064
Overexpression of Far Upstream Element Binding Proteins
Authors: Malz Mona , Weber Achim , Singer Stephan , Riehmer Vera , Bissinger Michaela , Riener Marc-Oliver , Longerich Thomas , Soll Christopher , Vogel Arndt , Angel Peter , Schirmacher Peter , Breuhahn Kai
Published: May 2009

Microtubule-dependent effects are partly regulated by factors that coordinate polymer dynamics such as the microtubule-destabilizing protein stathmin (oncoprotein 18). In cancer cells, increased microtubule turnover affects cell morphology and cellular processes that rely on microtubule dynamics such as mitosis and migration. However, the molecular mechanisms deregulating modifiers of microtubule activity in human hepatocarcinogenesis are poorly understood. Based on profiling data of human hepatocellular carcinoma (HCC), we identified far upstream element binding proteins (FBPs) as significantly coregulated with stathmin. Coordinated overexpression of two FBP family members (FBP-1 and FBP-2) in >70% of all analyzed human HCCs significantly correlated with poor patient survival.

In vitro

, FBP-1 predominantly induced tumor cell proliferation, while FBP-2 primarily supported migration in different HCC cell lines. Surprisingly, reduction of FBP-2 levels was associated with elevated FBP-1 expression, suggesting a regulatory interplay of FBP family members that functionally discriminate between cell division and mobility. Expression of FBP-1 correlated with stathmin expression in HCC tissues and inhibition of FBP-1 but not of FBP-2 drastically reduced stathmin at the transcript and protein levels. In contrast, further overexpression of FBP-1 did not affect stathmin bioavailability. Accordingly, analyzing nuclear and cytoplasmic areas of HCC cells revealed that reduced FBP-1 levels affected cell morphology and were associated with a less malignant phenotype.

Conclusion:

The coordinated activation of FBP-1 and FBP-2 represents a novel and frequent pro-tumorigenic mechanism promoting proliferation (tumor growth) and motility (dissemination) of human liver cancer cells. FBPs promote tumor-relevant functions by at least partly employing the microtubule-destabilizing factor stathmin and represent a new potential target structure for HCC treatment. (Hepatology 2009.)
Cyclooxygenase-2 prevents fas-induced liver injury through up-regulation of epidermal growth factor receptor #
Authors: Li Guiying , Han Chang , Xu Lihong , Lim Kyu , Isse Kumiko , Wu Tong
Published: May 2009

Cyclooxygenase-2 (COX-2)–derived prostaglandins participate in a number of pathophysiological responses such as inflammation, carcinogenesis, and modulation of cell growth and survival. This study used complementary approaches of COX-2 transgenic (Tg) and knockout (KO) mouse models to evaluate the mechanism of COX-2 in Fas-induced hepatocyte apoptosis and liver failure in vivo. We generated Tg mice with targeted expression of COX-2 in the liver by using the albumin promoter-enhancer–driven vector. The COX-2 Tg, COX-2 KO, and wild-type mice were treated with the anti-Fas antibody Jo2 (0.5 μg/g of body weight) for 4 to 6 hours, and the extent of liver injury was assessed by histopathology, serum aminotransferases, TUNEL staining, and caspase activation. The COX-2 Tg mice showed resistance to Fas-induced liver injury in comparison with the wild-type mice; this was reflected by the lower alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels, less liver damage, and less hepatocyte apoptosis (P < 0.01). In contrast, the COX-2 KO mice showed significantly higher serum ALT and AST levels, more prominent hepatocyte apoptosis, and higher levels of caspase-8, caspase-9, and caspase-3 activity than the wild-type mice (P < 0.01). The COX-2 Tg livers expressed higher levels of epidermal growth factor receptor (EGFR) than the wild-type controls; the COX-2 KO livers expressed the lowest levels of EGFR. Pretreatment with a COX-2 inhibitor (NS-398) or an EGFR inhibitor (AG1478) exacerbated Jo2-mediated liver injury and hepatocyte apoptosis. Conclusion: These findings demonstrate that COX-2 prevents Fas-induced hepatocyte apoptosis and liver failure at least in part through up-regulation of EGFR. (Hepatology 2009.)
Myeloid derived suppressor cells inhibit natural killer cells in patients with hepatocellular carcinoma via the NKp30 receptor #
Authors: Hoechst Bastian , Voigtlaender Torsten , Ormandy Lars , Gamrekelashvili Jaba , Zhao Fei , Wedemeyer Heiner , Lehner Frank , Manns Michael P. , Greten Tim F. , Korangy Firouzeh
Published: May 2009

Several immune suppressive mechanisms that evade the host immune response have been described in patients with hepatocellular carcinoma (HCC); one of these mechanisms is expansion of myeloid-derived suppressor cells (MDSCs). MDSCs have been shown to inhibit T cell responses in tumor-bearing mice, but little is known about these cells in humans. Here, we have analyzed and characterized the effect of MDSCs on the innate immune system, in particular, their interaction with natural killer (NK) cells in patients with HCC. MDSCs from patients with HCC inhibited autologous NK cell cytotoxicity and cytokine secretion when cultured together in vitro. This suppression was dependent on cell contact, but did not rely on the arginase activity of MDSCs, which is a hallmark function of these cells. However, MDSC-mediated inhibition of NK cell function was dependent mainly on the NKp30 on NK cells. Conclusion: Our study suggests a new role for MDSCs in patients with HCC in disarming the innate immune system and further contributing to the immune suppressor network in these patients. These findings have important implications when designing immunotherapy protocols. (Hepatology 2009.)
South Korean managerial reactions to voicing discontent: The effects of employee attitude and employee communication styles
Authors: Kim Tae‐Yeol , Rosen Benson , Lee Deog‐Ro
Published: May 2009

Using a scenario‐based experiment, this study examined how employee attitude and employee communication styles affected managers' reactions to employees' objections to a company policy. In the experiment, employee attitude (cynical versus trusting) and employee communication styles (aggressive versus diplomatic) were manipulated, and managers' reactions to voicing discontent were assessed through a questionnaire. Based on a sample of 185 middle managers working in various organizations in South Korea, the results showed that managers were more likely to engage in social undermining and were less likely to provide social support when cynical (rather than trusting) employees objected to a company policy. Also, attributed motives (i.e., personal attack and health concern) fully mediated the relationship between employee attitude and social support and social undermining. In addition, managers more likely attributed the objection to moral concerns when trusting (rather than cynical) employees communicated in an aggressive manner. Copyright © 2009 John Wiley & Sons, Ltd.
Identification of arid phases during the last 50 cal. ka BP from the Fuentillejo maar‐lacustrine record (Campo de Calatrava Volcanic Field, Spain)
Authors: Vegas Juana , Ruiz‐Zapata Blanca , Ortiz José E. , Galán Luis , Torres Trinidad , García‐Cortés Ángel , Gil‐García María J. , Pérez‐González Alfredo , Gallardo‐Millán José L.
Published: May 2009

Geochemical (element analysis, molecular analysis of organic compounds), physical, palynological, mineralogical and sedimentary facies analysis were performed to characterise the sedimentary record in Fuentillejo maar‐lake in the Central Spanish Volcanic Field of Campo de Calatrava, in order to reconstruct the palaeoenvironmental and palaeoclimatic processes which controlled vegetation patterns and deposition of different sedimentary facies. The upper 20 m of core FUENT‐1 show variations in clastic input, water chemistry, vegetation and organic fraction sources in the lake throughout the Late Pleistocene and Holocene. The temporal framework provided by 14C accelerator mass spectrometry dating allows assigning the sequence to the last 50 cal. ka BP. Arid phases identified in the FUENT‐1 sequence are correlated to Heinrich events (HE) and to stadials of the Dansgaard/Oeschger (D/O) cycles. Siliciclastic facies with high magnetic susceptibility values, high Juniperus pollen content, a low Paq index (aquatic macrophysics proxy index), a decrease in the relative percentage of the n‐C27 and an increase in the n‐C31 alkanes are indicative of arid and colder climatic events related to HE 2, HE 1 and the Younger Dryas (YD). Similar short cold and arid phases during the Holocene were identified at 9.2–8.6, 7.5–7 and 5.5–5 cal. ka BP. In dolomite–mud facies, the pollen data show an increase in the herbs component, mainly – Chenopodiaceae, Artemisia and Ephedra – steppe taxa; a low Paq index, a decrease in the relative percentage of the n‐C27 alkane and an increase in the n‐C31 alkane are also observed. This facies was probably the result of lower lake levels and more saline–alkaline conditions, which can be interpreted as linked to arid–warm periods. These warm and arid phases were more frequent during Marine Isotope Stage (MIS) 3 and the interstadials of MIS 2. HE 4, HE 2, HE 1 and the YD in core FUENT‐1 were immediately followed by increases of warm steppe pollen assemblages that document rapid warming similar to the D/O cycles but do not imply increasing humidity in the area. Fuentillejo hydrology is controlled by changes in the atmospheric and oceanic systems that operated on the North Atlantic region at millennial scale during the last 50 cal. ka BP. Copyright © 2009 John Wiley & Sons, Ltd.
Sea‐level changes since the Last Glacial Maximum: an appraisal of the IPCC Fourth Assessment Report
Authors: Gehrels Roland
Published: May 2009

The IPCC Fourth Assessment Report (AR4) stated that global sea level rose by about 120 m between the Last Glacial Maximum (LGM) and 3–2 ka and did not rise again until the late 19th century. A review of relevant literature demonstrates that the rise may have been larger (by 10–15 m), that the timing of stabilisation is poorly constrained (within the last 7 ka BP), and that the onset of modern rates of sea‐level rise is not synchronous and uniform across the globe. The LGM lowstand as defined in the AR4 is based on the ‘classic’ Barbados sea‐level history, but the sea‐level curve from this island may not be an accurate ‘eustatic’ approximation if glacial isostatic adjustment (GIA) processes were significant, as suggested by various authors. The Barbados sea‐level curve revealed the existence of meltwater pulse (MWP) 1a at around 14 000 cal. a BP. Questions about the source and causal mechanism of MWP 1a are still being explored by field scientists and GIA modellers. These problems have direct relevance for contemporary measurements of ice mass changes, because space geodetic measurements rely on information provided by GIA models to separate land motion from ice mass changes. Global patterns of Holocene sea‐level change are controlled by regional sea‐level variability, not only through isostatic and tectonic processes, but also through steric effects, longer‐wavelength gravitational changes produced by changing ice–ocean mass flux and hemispheric‐scale perturbations in the Earth's rotation. ‘Eustasy’ is therefore merely a concept, not a measurable quantity. Constraining the late Holocene ice melt contribution to global sea‐level rise and determining regional sea‐level rise patterns in the 18th and 19th centuries are important future tasks for sea‐level scientists; these will establish the baseline contributions to 20th‐ and 21st‐century sea‐level rise and will help to determine the causes of modern rates of sea‐level rise. Constraining historical sea‐level accelerations and short‐term ice‐mass flux will aid models of ice‐sheet dynamics and help to reduce current uncertainties in future sea‐level predictions. The AR4 shows that regional sea‐level variability is clearly present in sea‐level change patterns for the past 50 a and an important challenge for the next IPCC assessment is to incorporate this variability into regional future sea‐level rise scenarios. Copyright © 2009 John Wiley & Sons, Ltd.
The evolution of the guild of large Carnivora of the British Isles during the Middle and Late Pleistocene
Authors: Turner Alan
Published: May 2009

Recent refinements to the dating of a number of Middle and Late Pleistocene localities and fossil mammal assemblages from the British Isles, and their correlation with Marine Isotope Stages (MIS), permit a more detailed assessment of the evolution of the guild of larger Carnivora. By around 0.4–0.5 Ma (MIS 13–11) or just after, the more archaic elements of the guild, such as the sabretoothed catHomotherium latidens, the medium‐sized pantherinePanthera gombaszoegensisand the large dogCanis lycaonoides, had disappeared and had been replaced, or were being replaced, by extant species such as lion (Panthera leo), spotted hyaena (Crocuta crocuta) and the wolf (Canis lupus), although claims for a last‐glaciation appearance – or reappearance – ofHomotheriumrequire assessment. During MIS 5a this guild seems to have been temporarily replaced by a more restricted one of wolf in conjunction with a very large brown bear (Ursus arctos), together with a reduced prey fauna of bison and reindeer. Final extinction ofCrocutaand lion in these islands took place towards the end of MIS 3, arguably prior to the Last Glacial Maximum. Copyright © 2009 John Wiley & Sons, Ltd.
Beliefs of and attitudes toward political advertising: An exploratory investigation
Authors: Jin Hyun Seung , An Soontae , Simon Todd
Published: May 2009

The major goals of this study were to identify voters' belief structures about political advertising, develop a scale to measure beliefs, and examine how the identified beliefs are related to overall attitudes toward political advertising. The reliabilities, factor structure, and validity tests indicate that five belief dimensions—information, veracity, cynicism, money politics, and entertainment—have sound and stable properties. The scale demonstrates that voters assess political advertising at the instrumental level (e.g., information, veracity, and entertainment) as well as the institutional level (e.g., cynicism and money politics). The results showed that not all beliefs predicted overall attitudes. Furthermore, the results indicated that political involvement was a significant factor in influencing both beliefs and attitudes. © 2009 Wiley Periodicals, Inc.
Serotonin and Parkinson's disease: On movement, mood, and madness
Authors: Fox Susan H. , Chuang Rosalind , Brotchie Jonathan M.
Published: May 2009

An appreciation of the multiple roles that serotonin (5‐HT) may play in Parkinson's disease (PD) has increased in recent years. Early pathological studies in PD demonstrated nonselective reductions of 5‐HT in brain tissue but little correlation to comorbidities such as dyskinesia and mood disturbance. This, combined with treatment failures using serotonergic drugs in comparison to levodopa, meant the field was largely neglected until recently. The multitude of subtypes of 5‐HT receptors in the brain and an increased understanding of the potential function 5‐HT may play in modulating other neurotransmitter systems, including dopamine, GABA, and glutamate, have meant an expansion in efforts to develop potential serotonergic drugs for both motor and nonmotor symptoms in PD. However, several unanswered questions remain, and future studies need to focus on correlating changes in 5‐HT neurotransmission in both pathological andin vivoimaging studies with a full clinical phenotype. © 2009 Movement Disorder Society
Alpha‐synuclein and familial Parkinson's disease
Authors: Pankratz Nathan , Nichols William C. , Elsaesser Veronika E. , Pauciulo Michael W. , Marek Diane K. , Halter Cheryl A. , Wojcieszek Joanne , Rudolph Alice , Pfeiffer Ronald F. , Foroud Tatiana ,   for the Parkinson Study Group – PROGENI Investigators
Published: May 2009

Whole gene duplications and triplications of alpha‐synuclein (SNCA) can cause Parkinson's disease (PD), and variation in the promoter region (Rep1) and 3' region of SNCA has been reported to increase disease susceptibility. Within our cohort, one affected individual from each of 92 multiplex PD families showing the greatest evidence of linkage to the region around SNCA was screened for dosage alterations and sequence changes; no dosage or non‐synonymous sequence changes were found. In addition, 737 individuals (from 450 multiplex PD families) that met strict diagnostic criteria for PD and did not harbor a known causative mutation, as well as 359 neurologically normal controls, were genotyped for the Rep1 polymorphism and four SNPs in the 3′ region of SNCA. The four SNPs were in high LD (r2 > 0.95) and were analyzed as a haplotype. The effects of the Rep1 genotype and the 3′ haplotype were evaluated using regression models employing only one individual per family. Cases had a 3% higher frequency of the Rep1 263 bp allele compared with controls (OR = 1.54; empirical P‐value = 0.02). There was an inverse linear relationship between the number of 263 bp alleles and age of onset (empirical P‐value = 0.0004). The 3′ haplotype was also associated with disease (OR = 1.29; empirical P‐value = 0.01), but not age of onset (P = 0.40). These data suggest that dosage and sequence changes are a rare cause of PD, but variation in the promoter and 3′ region of SNCA convey an increased risk for PD. © 2009 Movement Disorder Society
Trunk muscle strength, but not trunk rigidity, is independently associated with bone mineral density of the lumbar spine in patients with Parkinson's disease
Authors: Pang Marco Y.C. , Mak Margaret K.Y.
Published: May 2009

Previous literature suggested that muscle forces applied to the skeleton may be an important factor in increasing bone mineral density (BMD). This purpose of this study was to determine whether trunk rigidity and trunk muscle strength were associated with lumbar spine BMD in patients with Parkinson's disease (PD). Forty‐three PD patients and 29 controls participated in this study. Dual‐energy X‐ray absorptiometry was used to measure lumbar spine BMD of PD patients. Additionally, an isokinetic dynamometer was used to evaluate trunk rigidity and trunk muscle strength of all subjects. The results showed that PD patients had significantly lower trunk muscle strength, but more trunk rigidity than controls by 46.6 and 162.8%, respectively (P < 0.001). In bivariate correlation analysis, lumbar spine BMD was significantly related to trunk muscle strength (r = 0.475, P = 0.001), but not trunk rigidity (r = 0.271, P = 0.079). In multiple regression analysis, after adjusting for relevant factors, only trunk muscle strength remained independently associated with lumbar spine BMD, accounting for 10.0% of the variance (R2 = 0.342, F5,37 = 3.838, P = 0.007). Trunk muscle strength, but not trunk rigidity, is independently associated with lumbar spine BMD in patients with PD. Further randomized controlled studies are required to determine whether trunk muscle strengthening exercise is effective in enhancing lumbar spine BMD. © 2009 Movement Disorder Society