Psychometric evaluation and validation of the German version of the Acute Stress Disorder Scale across two distinct trauma populations

Addressing the lack of self‐report tools for acute stress disorder assessment, the authors aimed at translating and evaluating the Acute Stress Disorder Scale (ASDS) into German. The scale was applied to parents of children following cardiopulmonary bypass surgery ( n = 61), and to patients with an acute cardiac event ( n = 52) within one month of illness‐related trauma. Indices of reliability, construct, and predictive validity with established measures of posttraumatic stress, anxiety, and depression suggest that the German ASDS is a psychometrically sound and valid instrument.

Outcome of patients after treatment for a squamous cell carcinoma of the oropharynx

Objectives: This study evaluates the oncologic outcome with regard to survival and locoregional tumor control in a cohort of patients with oropharyngeal squamous cell carcinoma (OPSCC) treated according to a uniform algorithm. Study Design: Retrospective chart review. Methods: A total of 427 consecutive patients with OPSCC were treated from 1990 to 2006. Treatment modalities were surgery alone (n = 102), surgery with adjuvant radio(chemo)therapy (n = 159), and primary radio(chemo)therapy (n = 166). Study endpoints were the five‐year overall survival (OS) and disease‐specific survival (DSS) stratified for primary tumor subsite, stage, T and N category, and age. Results: The five‐year OS and DSS for the entire cohort were 57.9% and 68.6%, respectively. OS and DSS for surgery alone were 70.3% and 76.5%, for surgery with radiation 66.6% and 78.9%, and for primary radiation 40.8% and 52.6%, respectively. Survival was significantly better for low stages (stage I/II vs. III/IV), small tumors (T1/2 vs. T3/4), limited nodal involvement (N0/1 vs. N2/3), and younger age at diagnosis. Conclusions: Together with our previous study on quality of life, we were able to show that our selection process gives excellent oncologic outcome in combination with high levels of function and quality of life. Surgery alone for early OPSCC and surgery followed by radiation for advanced OPSCC remain valuable treatment options. Primary radiochemotherapy is a strong alternative for patients who are not candidates for function‐preserving surgery. Laryngoscope, 119:534–540, 2009

BOOK REVIEW

COLIN LITTLE, GRAY A. WILLIAMS AND CYNTHIA D. TROWBRIDGE. 2009. The Biology of Rocky Shores, 2 nd edition. Oxford University Press. ISBN 978‐0198564904. 352 p. US$120

Hepatocyte transplantation in animal models

More than 30 years after the first hepatocyte transplant to treat the Gunn rat, the animal model for Crigler‐Najjar syndrome, there are still a number of impediments to hepatocyte transplantation. Numerous animal models are still used in work aimed at improving hepatocyte engraftment and/or long‐term function. Although other cell sources, particularly hepatic and extrahepatic stem cells, are being explored, adult hepatocytes remain the cells of choice for the treatment of liver diseases by cell therapy. In recent years, diverse approaches have been developed in various animal models to enhance hepatocyte transduction and amplification in vitro and cell engraftment and functionality in vivo . They have led to significant progress in hepatocyte transplantation for the treatment of patients with metabolic diseases and for bridging patients with acute injury until their own livers regenerate. This review presents and considers the results of this work with a special emphasis on procedures that might be clinically applicable. Liver Transpl 15:7–14, 2009. © 2008 AASLD.

c‐Fos accelerates hepatocyte conversion to a fibroblastoid phenotype through ERK‐mediated upregulation of paxillin‐Serine178 phosphorylation

Transforming growth factor β (TGF‐β) exerts an important role in the late steps of carcinogenesis by cooperating with Ras to induce cell motility and tumor invasion. The transcription complex AP‐1 has been implicated in the regulation of genes involved in motility and invasion, by mechanisms not yet delineated. We utilized a model of immortalized human hepatocytes (IHH) overexpressing c‐Fos (IHH‐Fos) or not (IHH‐C) to investigate the role of c‐Fos on cell motility in response to a prolonged treatment with TGF‐β, EGF or a combination of both. Cotreatment with EGF and TGF‐β, but neither cytokine alone, induced the conversion of hepatocytes to a fibroblastoid phenotype and increased their motility in Boyden chambers. EGF/TGF‐β cotreatment induced a higher effect on ERK phosphorylation compared to TGF‐β treatment alone. It also induced an increase in total and phosphorylated Ser 178 paxillin, a protein previously implicated in cell motility. This response was inhibited by two specific MEK inhibitors, indicating the involvement of the ERK pathway in paxillin activation. Overexpression of c‐Fos correlated with increased cell scattering and motility, higher levels of ERK activation and phospho Ser 178 paxillin, increased levels of EGF receptor (EGF‐R) mRNA and higher EGF‐R phosphorylation levels following EGF/TGF‐β cotreatment. Conversely, siRNA‐mediated invalidation of c‐Fos delayed the appearance of fibroblastoid cells, decreased EGF‐R mRNA and downregulated ERK and Ser 178 paxillin phosphorylations, indicating that c‐Fos activates hepatocyte motility through an EGF‐R/ERK/paxillin pathway. Since c‐Fos is frequently overexpressed in hepatocarcinomas, this newly identified mechanism might be involved in the progression of hepatic tumors in vivo. © 2008 Wiley‐Liss, Inc.

Mitochondrial bioenergetic background confers a survival advantage to HepG2 cells in response to chemotherapy

Cancer cells mainly rely on glycolysis for energetic needs, and mitochondrial ATP production is almost inactive. However, cancer cells require the integrity of mitochondrial functions for their survival, such as the maintenance of the internal membrane potential gradient (ΔΨm). It thus may be predicted that ΔΨm regeneration should depend on cellular capability to produce sufficient ATP by upregulating glycolysis or recruiting oxidative phosphorylation (OXPHOS). To investigate this hypothesis, we compared the response to an anticancer agent chloroethylnitrosourea (CENU) of two transformed cell lines: HepG2 (hepatocarcinoma) with a partially differentiated phenotype and 143B (osteosarcoma) with an undifferentiated one. These cells types differ by their mitochondrial OXPHOS background; the most severely impaired being that of 143B cells. Treatment effects were tested on cell proliferation, O 2 consumption/ATP production coupling, ΔΨm maintenance, and global metabolite profiling by NMR spectroscopy. Our results showed an OXPHOS uncoupling and a lowered ΔΨm, leading to an increased energy request to regenerate ΔΨm in both models. However, energy request could not be met by undifferentiated cells 143B, which ATP content decreased after 48 h leading to cell death, while partially differentiated cells (HepG2) could activate their oxidative metabolism and escape chemotherapy. We propose that mitochondrial OXPHOS background confers a survival advantage to more differentiated cells in response to chemotherapy. This suggests that the mitochondrial bioenergetic background of tumors should be considered for anticancer treatment personalization. © 2009 Wiley‐Liss, Inc.

Association of corticobasal degeneration and Huntington's disease: Can Tau aggregates protect Huntingtin toxicity?

Dysfunction of the subthalamic nucleus induces behavioral and movement disorders in monkeys

High‐frequency stimulation of the subthalamic nucleus (STN) in parkinsonian patients is reported to induce psychiatric effects. The likely explanation for these effects is the partitioning of the STN into sensorimotor, associative, and limbic anatomo‐functional territories. Thus, a specific neuronal dysfunction of the STN sensorimotor territory could lead to abnormal movements, whereas a dysfunction of the associative or limbic territory could lead to behavioral disturbances. To test this hypothesis, neuronal dysfunction of the STN was induced by microinjections of the GABA agonist muscimol, or antagonist bicucculline, in various parts of the nucleus in three monkeys. Stereotyped behaviors (licking and biting fingers) and/or violent hyperactivity were obtained with bicuculline injected into the anteromedial, associative, and limbic territories, whereas injections of muscimol induced no major effects. Abnormal limb movements (contralateral ballism) were obtained after muscimol or bicuculline injections into the posterolateral, sensorimotor territory. Control injections localized around the STN induced other effects (mainly torticollis), which underlines the specificity of STN injection effects. Our study supports the hypothesis that the anteromedial part of the STN is involved in behavioral control. © 2009 Movement Disorder Society

Brain dopaminergic modulation associated with executive function in Parkinson's disease

The progressive development of deficits in executive functions, including action planning, is a well‐known complication of Parkinson's disease. A dysfunction of the prefrontal lobe, which is known to be involved in the control of inhibitory processes, could explain the difficulties in initiating behavior or inhibiting ongoing actions in patients with PD. The strong dopaminergic innervation of the prefrontal cortex raises questions about the putative effects of dopa therapy on this cognitive impairment. In the present study, we used fMRI to examine the functional influence of dopa therapy on neural activity during a go/no‐go task in nine patients with and without levodopa treatment and in matched controls. Whereas the patient and control subjects exhibited the same performance during the go/no‐go task, different patterns of brain activation were observed depending on the dopaminergic status. The drug‐off state was characterized by more widely distributed brain activity, mainly in the bilateral caudate. Levodopa did not fully restore normal brain activation and induced changes in the pattern of cingulate cortex activity, which was more pronounced in the rostral part in the drug‐off state and in the caudal part after levodopa intake. These results support the idea of a critical role for dopamine in the control of executive functions in patients with PD. © 2009 Movement Disorder Society

Comparison of weight gain and energy intake after subthalamic versus pallidal stimulation in Parkinson's disease

To compare body mass index (BMI) and daily energy intake (DEI) after subthalamic versus pallidal deep brain stimulation (DBS). Weight gain following DBS in Parkinson's disease patients remains largely unexplained and no comparison of subthalamic and pallidal (GPi) stimulation has yet been performed. BMI and DEI, dopaminergic drug administration and motor scores were recorded in 46 patients with PD before STN (n = 32) or GPi (n = 14) DBS and 3 and 6 months after. At M6, BMI had increased by an average of 8.4% in the STN group and 3.2% in the GPi group. BMI increased in 28 STN and 9 GPi patients. This increase was significantly higher in the STN group ( P < 0.048) and the difference remained significant after adjustment for reduced dopaminergic medication; 28.6% of GPi patients were overweight at 6 months (14.3% preoperatively) versus 37.5% of STN patients (21.9% preoperatively). Changes in BMI were negatively correlated with changes in dyskinesia in the GPi–DBS group. Food intake did not change in the two groups, either quantitatively or qualitatively. Frequent weight gain, inadequately explained by motor improvement or reduced dopaminergic drug dosage, occurred in subthalamic DBS patients. The difference between groups suggests additional factors in the STN group, such as homeostatic control center involvement. © 2009 Movement Disorder Society