bluuebunny/crossref_metadata_2025 huggingface dataset:
New Prediction Rule for Mortality in Acute Mesenteric Ischemia
Authors: Haga Yoshio , Odo Masaharu , Homma Masato , Komiya Kenichi , Takeda Kazunori , Koike Shoichiro , Takahashi Tadateru , Hiraka Kiyohisa , Yamashita Haruhiro , Tanakaya Kohji
Published: June 2009

Objective: Acute mesenteric ischemia is potentially fatal, but prognostic factors have not yet been established. This study was undertaken to elucidate them. Methods: This is a retrospective cohort study, consisting of 110 patients who had been treated in the past 5 years, from 26 national hospitals in Japan. Results: The overall in-hospital mortality rate was 51%. Logistic regression analysis demonstrated two independent prognostic factors, electrocardiogram scale with an odds ratio of 1.7 (95% CI 1.2–2.4) and shock index of 11 (95% CI 1.5–80). A stepwise analysis gave a prediction equation for in-hospital mortality (R) using these variables and age score. We further modified this equation to a simpler scoring system (S) using the same variables. Both R and S showed a good discriminatory ability as determined by areas under the receiver-operating characteristic curve (0.83, 95% CI: 0.74–0.91 for R; 0.82, 95% CI 0.74–0.91 for S). The observed mortality rates increased as the R or S increased (19% at R <0.25, 41% at 0.25 ≤ R <0.6, 85% at R ≥0.6; 19% at S ≤2, 37% at S of 3 or 4, 91% at S ≥5). Conclusion: The new prediction rules can be used at any hospital and may be promising tools for medical decision-making, informed consent and reviewing quality of care.
Analysis of Fat Digestive and Absorptive Function after Subtotal Gastrectomy by a 13C-Labeled Mixed Triglyceride Breath Test
Authors: Nakamura Hiroyuki , Murakami Yoshiaki , Morifuji Masahiko , Uemura Kenichiro , Hayashidani Yasuo , Sudo Takeshi , Ohge Hiroki , Sueda Taijiro
Published: June 2009

Background/Aim: In the choice of reconstructions, digestive and absorptive disturbances, resulting in weight loss after subtotal gastrectomy, remain a problem. The aim of this study was to compare fat absorptive function after Billroth I (B-I) and Roux-en-Y (RY) reconstructions after subtotal gastrectomy for gastric cancer. Methods: A 13C-labeled mixed triglyceride breath test was performed in 31 patients after subtotal gastrectomy and in 15 healthy volunteers to assess fat digestive and absorptive function. Seventeen B-I reconstructions and 14 RY reconstructions were performed after subtotal gastrectomy. Fat digestive and absorptive function was determined by percent 13CO2 cumulative dose at 7 h. Relationship between fat absorptive function and perioperative factors were analyzed. Results: Gender distribution, mean age, pathological staging, level of lymph node dissection, preservative procedure of the vagus nerve and mean follow-up period in the two surgical groups did not differ significantly. Only the type of reconstruction (p = 0.024) was associated with differences in fat digestive and absorptive function by univariate analysis: B-I reconstruction was superior to RY reconstruction. Conclusions: Fat digestive and absorptive function after B-I reconstruction was superior to that after RY reconstruction, probably because the B-I reconstruction was the procedure that permitted food passage through the duodenum.
CT/MR Image Fusion in the Postoperative Assessment of Electrodes Implanted for Deep Brain Stimulation
Authors: O’Gorman Ruth L. , Jarosz Josef M. , Samuel Michael , Clough Chris , Selway Richard P. , Ashkan Keyoumars
Published: June 2009

Background/Aims: Stereotactic postoperative imaging is essential for verification of the position of electrodes implanted for deep brain stimulation (DBS). MRI offers superior visualisation of the DBS targets relative to CT, but previous adverse incidents have heightened concerns about risks of postoperative MRI. Preoperative MRI fused with postoperative CT offers an alternative method for evaluating electrode position, but before this method can be clinically applied, the image registration accuracy must be established. The purpose of this study was to quantitatively assess the accuracy of three different image registration and fusion methods. Methods: Preoperative stereotactic MRI and postoperative stereotactic CT were acquired from 20 patients under- going DBS surgery (35 electrodes in total). The postoperative CT was registered and fused with the preoperative MRI, using three different registration algorithms. The position of each electrode tip was determined in stereotactic coordinates both in the (unfused) postoperative CT and the fused CT/MRI. The difference in tip position between the CT and fused CT/MRI was used to evaluate the registration accuracy. Results: The mean error along the lateral, anteroposterior, and vertical axes was 0.5, 0.5, and 1 mm, respectively. Conclusions: CT/MRI fusion provides a safe, practical technique for postoperative identification of DBS electrodes.
Stereotactic Atlas-Based Depth Electrode Localization in the Human Amygdala
Authors: Oya Hiroyuki , Kawasaki Hiroto , Dahdaleh Nader S. , Wemmie John A. , Howard III Matthew A.
Published: June 2009

Background: The efficacy of stereotactic neurosurgery procedures is critically dependent on the accuracy of the device placement procedure. The first step in this process involves correctly identifying the target location in three-dimensional brain space. In some clinical applications, this targeting process cannot be accomplished using MRI images of gross anatomical structures alone. The amygdala complex is a case in point, in that it consists of multiple histologically defined subnuclei with different functional characteristics. Methods: In this report, we describe an elastic atlas brain-morphing method that projects amygdala subnuclear anatomical information onto the MRI volumes of individual subjects. Results: The accuracy of this method was tested in 5 representative subjects using quantitative image-matching analytical techniques. The results demonstrate a high degree of intersubject variability in medial temporal lobe anatomy, and markedly superior anatomical matching performance by the elastic morphing method compared to Affine transformation. Conclusion: Nonlinear elastic morphing technique provides superior performance on fitting atlas templates to individual brain. The strengths and limitations of this and other atlas morphing methods are discussed in the context of emerging functional neurosurgery applications.
Automated 3-Dimensional Brain Atlas Fitting to Microelectrode Recordings from Deep Brain Stimulation Surgeries
Authors: Luján J. Luis , Noecker Angela M. , Butson Christopher R. , Cooper Scott E. , Walter Benjamin L. , Vitek Jerrold L. , McIntyre Cameron C.
Published: June 2009

Objective: Deep brain stimulation (DBS) surgeries commonly rely on brain atlases and microelectrode recordings (MER) to help identify the target location for electrode implantation. We present an automated method for optimally fitting a 3-dimensional brain atlas to intraoperative MER and predicting a target DBS electrode location in stereotactic coordinates for the patient. Methods: We retrospectively fit a 3-dimensional brain atlas to MER points from 10 DBS surgeries targeting the subthalamic nucleus (STN). We used a constrained optimization algorithm to maximize the MER points correctly fitted (i.e., contained) within the appropriate atlas nuclei. We compared our optimization approach to conventional anterior commissure-posterior commissure (AC/PC) scaling, and to manual fits performed by four experts. A theoretical DBS electrode target location in the dorsal STN was customized to each patient as part of the fitting process and compared to the location of the clinically defined therapeutic stimulation contact. Results: The human expert and computer optimization fits achieved significantly better fits than the AC/PC scaling (80, 81, and 41% of correctly fitted MER, respectively). However, the optimization fits were performed in less time than the expert fits and converged to a single solution for each patient, eliminating interexpert variance. Conclusions and Significance: DBS therapeutic outcomes are directly related to electrode implantation accuracy. Our automated fitting techniques may aid in the surgical decision-making process by optimally integrating brain atlas and intraoperative neurophysiological data to provide a visual guide for target identification.
Dorsal Root Entry Zone Lesions for Phantom Limb Pain with Brachial Plexus Avulsion: A Study of Pain and Phantom Limb Sensation
Authors: Zheng Zhe , Hu Yongsheng , Tao Wei , Zhang Xiaohua , Li Yongjie
Published: June 2009

Background: Lesions in the dorsal root entry zone (DREZ) have been shown to be significantly effective in relieving the pain of brachial plexus avulsion (BPA), but they have a limited effect on phantom limb pain (PLP). There is still the question remaining of whether DREZ lesions are effective in treating PLP in cases of BPA. Methods: Our study includes 14 post-traumatic patients with BPA and upper limb amputation. All developed PLP and underwent DREZ lesions. After the surgery, patients were asked to estimate the global percent of pain relief (0–100%). The phantom limb sensation (PLS) was also inquired after. Results: Overall, 9 (64.3%) of 14 patients had satisfactory pain relief; the mean follow-up was 15.2 ± 6.6 months. Among the 9 patients with satisfactory pain relief, PLS had altered in 6 (66.7%), while, in the other 5 patients with poor pain relief, none had experienced alterations in PLS. Conclusion: DREZ lesions are effective in the treatment of PLP with BPA. Alteration in PLS after the surgery may be a predictive factor for good pain relief. The good response of PLP patients with BPA to DREZ lesions suggests that an evaluation of the cervical dorsal roots should be conducted in patients with post-traumatic PLP.
The Hippocampus and Nucleus Accumbens as Potential Therapeutic Targets for Neurosurgical Intervention in Schizophrenia
Authors: Mikell Charles B. , McKhann Guy M. , Segal Solomon , McGovern Robert A. , Wallenstein Matthew B. , Moore Holly
Published: June 2009

Schizophrenia is a chronic and disabling psychiatric illness that is often refractory to treatment. Psychotic symptoms (e.g. hallucinations and delusions) in schizophrenia are reliably correlated with excess dopamine levels in the striatum, and have more recently been related to excess metabolic activity in the hippocampus. Multiple lines of evidence suggest that aberrantly high hippocampal activity may, via hippocampal connections with the limbic basal ganglia, drive excessive dopamine release into the striatum. In the present paper, we hypothesize that inhibition or stabilization of neural activity with high-frequency electrical stimulation of the hippocampus or nucleus accumbens, through different mechanisms, would treat the positive symptoms of schizophrenia. Thus, we suggest a direction for further experimentation aimed at developing neurosurgical therapeutic approaches for this devastating disease.
The Effects of L-NG-Nitroarginine in a Zymosan-Induced Multiple Organ Dysfunction Syndrome Model
Authors: Ozel H. , Yuksel B.C. , Berkem H. , Avsar F.M. , Guler G. , Iskit A.B. , Guc M.O. , Hengirmen S.
Published: June 2009

Background: The aim of this study was to investigate the role of nitric oxide in mesenteric ischemia, organ injury and survival in zymosan-induced multiple organ dysfunction syndrome (MODS) by using the nonselective nitric oxide synthase inhibitor L-NG-nitroarginine (L-NNA). Methods: Swiss albino mice (20–40 g) were used in the study. The animals were randomly divided into four groups. The first group was treated intraperitoneally with saline and served as the sham group for L-NNA. The second group was treated with zymosan (500 mg/kg). The mice in the third and fourth group received L-NNA (20 mg/kg), 1 and 6 h after saline or zymosan administration. Six hours after the administration of zymosan, animals were used for mesenteric arterial blood flow (MABF) measurements and then sacrificed for biochemical and histopathological analyses at the 18th hour. Results: In zymosan-treated animals, MABF was significantly lower than that of solvent saline-treated controls (controls: 4.7 ± 0.8 ml·min–1; zymosan: 1.7 ± 0.7 ml·min–1, p < 0.05). L-NNA did not prevent zymosan-induced MABF decrease (controls: 4.5 ± 0.8 ml·min–1; zymosan: 2.5 ± 1.4 ml·min–1, p <0.05). Also treatment with L-NNA has no beneficial effect on survival and organ injury in zymosan-induced MODS. Conclusion: In this study, inhibition of both inducible and constitutive nitric oxide synthase by L-NNA did not abolish the harmful effects of zymosan. L-NNA remains an agent without any therapeutic potential in this acute experimental model of MODS.
Phase II Study of Biweekly Docetaxel and S-1 Combination Therapy for Advanced or Recurrent Gastric Cancer
Authors: Kakeji Yoshihiro , Oki Eiji , Egashira Akinori , Sadanaga Noriaki , Takahashi Ikuo , Morita Masaru , Emi Yasunori , Maehara Yoshihiko
Published: June 2009

Objective: This phase II study evaluated the toxicity and efficacy of a novel dosing schedule of docetaxel and S-1 as treatment for advanced gastric cancer. Methods: Patients with measurable advanced or recurrent gastric cancer and no prior exposure to the investigational drugs were treated with intravenous docetaxel 35 mg/m2 on days 1 and 15, and oral S-1 80 mg/m2/day on days 1–14 every 4 weeks. The primary endpoint was objective response. Results: Thirty-five eligible patients were enrolled and received a total of 151 cycles of treatment (median 3, range 1–19). One complete response and 13 partial responses were observed, with an overall response rate of 40% (95% CI: 24–56%). Median progression-free survival and median overall survival times were 4.5 and 14.2 months, respectively. The most common grade 3–4 toxicities were neutropenia (23%) and leukocytopenia (15%). Conclusion: Biweekly docetaxel combined with S-1 is active in advanced or recurrent gastric cancer, and can be administered with proper management of adverse events in an outpatient clinic.
Poststroke Depression: Prevalence and Determinants in Brazilian Stroke Patients
Authors: Carod-Artal Francisco Javier , Ferreira Coral Luciane , Trizotto Daniele Stieven , Menezes Moreira Clarissa
Published: June 2009

Background: Poststroke depression (PSD) is one of the most important long-term adverse psychosocial consequences in stroke survivors. Our objective was to assess the prevalence of PSD in Brazilian stroke patients and identify significant associated factors. Methods: A cross-sectional study of stroke patients consecutively admitted for rehabilitation was conducted. The patients were evaluated by means of the NIH Stroke Scale, Mini-Mental State Examination, Barthel Index, Lawton Scale, modified Rankin Scale, Hospital Anxiety and Depression Scale (HADS), Geriatric Depression Scale (GDS) and MOS-Short Form 36. Patients with a HADS-depression subscale score ≥11 and/or GDS score ≥8 were classified as depressed. Results: Three hundred stroke survivors were assessed (mean age: 56.3 years; 51.7% males). Half (46.7%) of the stroke patients had an m-RS score ≤2. The proportion of stroke patients who scored ≥11 points on the HADS-depression and HADS-anxiety subscales were 19.2 and 23.7%, respectively. One third (29.7%) had a GDS mean score ≥8. The GDS scores significantly correlated (p < 0.0001) with the HADS-depression (r = 0.51) and HADS-anxiety subscales (r = 0.54). The prevalence of mood disorders was significantly higher in females than in males (24.8 vs. 14.2%; x2, p = 0.03). PSD was significantly associated (p < 0.0001) with work status (housewife), education level, lower social and cognitive functioning, dependence in the instrumental activities of daily living and presence of diabetes in the multivariable regression analysis (R adjusted = 0.32). Conclusions: PSD was highly prevalent in the chronic phase of stroke. Early detection and recognition of associated risk factors is important to treat and prevent PSD in a rehabilitation setting.
An Observational Study of Acute Stroke Care in Four Countries: The European Registers of Stroke Study
Authors: Wellwood I. , Langhorne P. , McKevitt C. , Bernhardt J. , Rudd A.G. , Wolfe C.D.A.
Published: June 2009

Background: The European Registers Of Stroke (EROS) project aimed to assess outcomes of stroke care across Europe, relating these to both case mix information from disease-specific population registers and the quality of stroke care provided at each centre. This included comparing information on quality of care with direct observation of the stroke care process in 4 centres. Methods: Direct non-participant observational methods were used on a purposive sample of first-stroke patients admitted within the past 14 days to an acute-stroke unit or ward that admits stroke patients in 4 urban hospital sites in London, UK, Dijon, France, Kaunas, Lithuania, and St. Petersburg, Russia. We recorded patient characteristics with levels of contact with multi-disciplinary team (MDT) members and contact with families and mobilization to build a collection of ‘snapshots’ of stroke care throughout the patients’ day. One independent observer undertook all observations over 1 day. Results: We observed differences between centres in the proportion of observations where patients were alone (lowest proportion in London, highest proportion in St. Petersburg) (p > 0.001), where patients had contact with MDT members (p > 0.001) and family, and where patients were out of bed/mobile (p > 0.001) (both with highest proportion in London, lowest proportion in St. Petersburg). Conclusions: Higher levels of contact with the MDT, family contact and mobilization were observed in the Western European centres than the Eastern European and Russian centres. Differences in case mix may explain some, but not all, of these differences. Direct observation has some limitations; however, it could be developed in future studies to help identify other key aspects of effective stroke care.
Association of White-Matter Lesions with Brain Atrophy Markers: The Three-City Dijon MRI Study
Authors: Godin Ophélia , Maillard Pauline , Crivello Fabrice , Alpérovitch Annick , Mazoyer Bernard , Tzourio Christophe , Dufouil Carole
Published: June 2009

Background: Brain atrophy and white-matter lesions (WML) are common features at cerebral MRI of both normal and demented elderly people. In a population-based study of 1,792 elderly subjects aged 65–80 years, free of dementia, who had a cerebral MRI at entry, we investigated the relationship between WML volume and brain atrophy markers estimated by hippocampal, gray matter (GM) and cerebrospinal fluid (CSF) volumes. Methods: An automated algorithm of detection and quantification of WML was developed, and voxel-based morphometry methods were used to estimate GM, CSF and hippocampal volumes. To evaluate the relation between those volumes and WML load, we used analysis of covariance and multiple linear regression models adjusting for potential confounders and total intracranial volumes. Results: Age was highly correlated with WML load and all brain atrophy markers. Total WML volume was negatively associated with both GM (β = –0.03, p < 0.0001) and hippocampal volumes (β = –0.75, p = 0.0009) and positively with CSF volumes (β = 0.008, p = 0.02) after controlling for sex, age, education level, hypertension and apolipoprotein E genotype. Evidence for a relationship between brain atrophy markers and WML was stronger for periventricular WML. We found that the relationship between WML and hippocampal volumes was independent of other brain tissue volumes. Conclusion: These results suggest that, in the brain of nondemented elderly subjects, degenerative processes and vascular changes co-occur and are related independently of vascular risk factors.
Cellular Receptors for Foot and Mouth Disease Virus
Authors: Ruiz-Sáenz J. , Goez Y. , Tabares W. , López-Herrera A.
Published: June 2009

Foot-and-mouth disease virus (FMDV), the prototype member of the Aphthovirus genus, is a single-stranded, positive-sense RNA genome virus, which affects many domestic livestock cloven-hoofed animals, causing substantial lost of milk in dairy cattle, reduction in the growth rate of meat animals, among others. It has been shown that the virus can enter to the cells using different pathways; the main one binding integrins via the clathrin-mediated endocytosis pathway, trafficking throughout the acidified endocytic vesicles, where its capsid rapidly dissociates, resulting in the release of the RNA genome, and the second one using heparan sulfate in which FMDV enters to the cells using the caveola-mediated endocytosis pathway and that caveolae can associate and traffic with endosomes. Different integrins had been involved as FMDV receptors (αvβ1, αvβ3, α5β1, αvβ6, αvβ8); this review will try to resume the basic information about FMDV receptors from the last years to the present and will resume the most important in vitro and in vivo studies to elucidate the role of this receptor on the infection.
Prevalence of Primary Focal or Segmental Dystonia in Adults in the District of Foggia, Southern Italy: A Service-Based Study
Authors: Papantonio Anna Maria , Beghi Ettore , Fogli Danilo , Zarrelli Michele , Logroscino Giancarlo , Bentivoglio Annarita , Simone Pasqualino , Tonali Pietro , Specchio Luigi Maria
Published: June 2009

Background: Primary focal or segmental dystonia is a rare clinical condition including early-onset dystonia, which has the tendency to generalize, and late-onset dystonia, which may be focal or segmental. The prevalence of late-onset dystonia ranges from 30 to 7,320 cases per million, but no data are available in Italy. Methods: A service-based study was conducted in the period 1 January 2001 through 31 December 2002 in the administrative district of Foggia, southern Italy (population 541,653). Cases were traced through hospital discharge diagnosis, botulinum toxin services, day hospital access, ear, nose and throat, ophthalmology and orthopedic surgery specialists, and territorial outpatient services. Inclusion criteria were age 17 years or older, residency in the study area and a diagnosis of primary focal/segmental dystonia. Results: A total of 69 patients were included, giving a crude prevalence of 127.4 per 1,000,000 (women: 146.4; men: 107.0; age 18–34 years: 39.2; 35–54 years: 98.7; 55–74 years: 273.6; 75+ years: 163.3). The standardized rate was 137.5 (95% confidence interval 107.0–174.6). Blepharospasm was the commonest clinical condition (prevalence 68.2), followed by cervical dystonia (prevalence 44.8). Conclusion: The prevalence of primary focal or segmental dystonia in Italy is in keeping with several other reports, but is lower than in studies performed in northern Europe, Minnesota, USA, and Japan. The difference in our results may be mostly explained by misdiagnosis, underascertainment of cases and a fairly limited observation period.
Adaptation of Skeletal Muscle Microvasculature to Increased or Decreased Blood Flow: Role of Shear Stress, Nitric Oxide and Vascular Endothelial Growth Factor
Authors: Hudlicka Olga , Brown Margaret D.
Published: June 2009

This review elucidates the roles of capillary haemodynamics, nitric oxide (NO) and vascular endothelial growth factor (VEGF) in the remodelling of skeletal muscle microcirculation in response to increased (electrical stimulation) or decreased (chronic ischaemia) blood flow. During early stages of stimulation-induced angiogenesis, up-regulation of VEGF and its receptor VEGF receptor 2 is dependent on shear stress and NO release, whereas later, involvement of NO in the expanding capillary bed appears to be VEGF/VEGF receptor 2 independent. Arteriolar growth most likely relies on mechanical wall stresses while growth factor involvement is less clear. By contrast, in muscles with restricted blood flow, increased VEGF/VEGF receptor 2 expression after ischaemia onset is not associated with changes in shear stress or hypoxia, or capillary growth. After several weeks, VEGF protein levels are lower than normal while modest angiogenesis takes place, a temporal mismatch that limits the utility of using growth factor levels during ischaemia to assess angiogenic potential. Chronic stimulation of ischaemic muscles restores their depressed endothelial-dependent arteriolar dilatation, increases capillary shear stress and VEGF receptor 2 and promotes capillary growth. In patients with peripheral vascular disease, electrical stimulation of ischaemic calf muscles increases blood flow, capillary surface area and muscle performance, offering an alternative ‘endogenous’ treatment to gene or cell therapy.
Defensins in Viral Infections
Authors: Ding Jian , Chou Yi-Ying , Chang Theresa L.
Published: June 2009

Defensins are antimicrobial peptides important to innate host defense. In addition to their direct antimicrobial effect, defensins modulate immune responses. Increasing evidence indicates that defensins exhibit complex functions by positively or negatively modulating infections of both enveloped and non-enveloped viruses. The effects of defensins on viral infections appear to be specific to the defensin, virus and target cell. Regulation of viral infection by defensins is achieved by multiple mechanisms. This review focuses on the interplay between defensins and viral infections, the mechanisms of action of defensins and the in vivo studies of the role of defensins in viral infections.
Differences in Cell Wall Thickness between Resistant and Nonresistant Strains of Mycobacterium tuberculosis: Using Transmission Electron Microscopy
Authors: Velayati Ali Akbar , Farnia Parissa , Ibrahim Tengku Azmi , Haroun Rafiuz Zaman , Kuan Ho Oi , Ghanavi Jalaledin , Farnia Poopak , Kabarei Ali Naghee , Tabarsi Payam , Omar Abdul Rahman , Varahram Mohammad , Masjedi Mohammad Reza
Published: June 2009

The ultrastructure of the cell wall of extensively drug-resistant (XDR), multidrug-resistant (MDR) and susceptible tuberculosis (TB) bacilli was viewed under transmission electron microscopy (TEM). Under the TEM, marked differences were observed in the thickness of their cell wall: 20.2 ±1.5 and 17.1 ±1.03 nm for the XDR and MDR TB bacilli, respectively, and 15.6 ± 1.3 nm for the susceptible isolates (p < 0.05). In MDR bacilli, thickening of the cell wall was observed in the intermediate electron-transparent layer (ETL) and outer electron-opaque layer, whereas in XDR TB cells the basal peptidoglycan layer was denser and almost fused with the ETL. Five to seven percent of XDR TB bacilli had the appearance of the stationary phase with cell wall thickness ranging from 21 to 26 nm (p < 0.001). Information provided in this study is of significant importance in terms of drug selection for effective treatment of resistant strains.
Sequencing and Expression of the Xylanase Gene 2 from Trichoderma reesei Rut C-30 and Characterization of the Recombinant Enzyme and Its Activity on Xylan
Authors: Jun He , Bing Yu , Keying Zhang , Xuemei Ding , Daiwen Chen
Published: June 2009

The Xyn2 gene, which encodes endo-β-1,4-xylanase2, in Trichoderma reesei Rut C-30 was amplified by PCR from first-strand cDNA synthesized on mRNA isolated from the fungus. The nucleotide sequence of the cDNA fragment was verified to encode 190-amino-acid residues of a protein with a calculated molecular mass of 21 kDa. The cDNA was cloned into pET30α expression vector and subsequently expressed in Escherichia coli under the control of strong bacteriophage T7 transcription and translation signals. The enzyme activity assay verified the recombinant protein as xylanase. The isoelectric point and highest activity were 7.5 and 1,600 U/mg, respectively. Like with the T. reesei Xyn2, the highest activity of the recombinant Xyn2 was at 50°C. However, the recombinant enzyme had an improved thermostability and more than 65% of its activity retained after 30 min incubation at 60°C. In addition, the recombinant Xyn2 was active over the range of pH 3.5–7.5 with maximum activity at pH 5.0. Using birchwood xylan, the determined apparent Km and kcat values were 0.15 mg/ml and 119.7 s–1, respectively. The enzyme was highly specific towards xylans and exhibited very low activity towards cellulosic substrates. Analysis of the products from birchwood xylan degradation confirmed that the enzyme was an endo-xylanase with xylobiose and xylose as the main degradation products. These properties should make the enzyme a suitable applicant in various industrial applications.
Developing the Blueprint for a Genetic Testing Registry
Authors: Javitt G. , Katsanis S. , Scott J. , Hudson K.
Published: June 2009

While the number of genetic tests continues to grow, publicly accessible information about the analytic and clinical validity of such tests is lagging. Information gaps impede informed decision making by health care providers and patients. Enhancing the transparency of information about what tests are being offered, for which indications tests are being offered, and the analytic and clinical validity of tests is a key prerequisite to ensuring test quality. A recent government recommendation for a mandatory genetic test registry has received wide stakeholder support but leaves many practical questions unanswered. We propose a ‘blueprint’ for the creation of a genetic test registry in order to expedite its implementation. We describe the goals of a registry, propose criteria for the inclusion of registrants and tests in the registry, and define the categories of information that should be included for such tests. We discuss the sources of legal authority that empower the government to mandate that a registry be established and identify the federal agencies with the relevant expertise and resources to do so. We conclude that establishing a registry is a critical first step in the development of a more transparent, quality-centered system of oversight that will better inform and protect the public.
What Can Interest Tell Us about Uptake of Genetic Testing? Intention and Behavior amongst Smokers Related to Patients with Lung Cancer
Authors: Sanderson S.C. , O’Neill S.C. , Bastian L.A. , Bepler G. , McBride C.M.
Published: June 2009

Background: Much of the research examining psychosocial aspects of genetic testing has used hypothetical scenarios, based on the largely untested assumption that hypothetical genetic testing intentions are good proxies for behavior. We tested whether hypothetical interest predicts uptake of genetic testing and whether factors that predict interest also predict uptake. Methods: Participants (n = 116) were smokers and related to patients with lung cancer, who completed a telephone survey. Interest in genetic testing for lung cancer risk was indicated by responding ‘definitely would’ to a Likert-style question. Internet-delivered genetic testing for lung cancer risk was then offered. Uptake was indicated by requesting the test and receiving the result. Results: 63% of participants said they ‘definitely would’ take the genetic test; uptake was 38%. Participants who said they ‘definitely would’ take the test were more likely than others to take the offered test (45% vs. 26%, p = 0.035). Interest was associated with attitudes towards genetic testing and motivation to quit smoking. Uptake was associated with motivation, prior awareness of genetic testing, and daily Internet use. Conclusion: Hypothetical interest only modestly predicts uptake of genetic testing. Interest in genetic testing likely reflects generally positive attitudes that are not good predictors of the choices individuals subsequently make.
Protein Kinase Cα, but Not PKCβ or PKCγ, Regulates Contractility and Heart Failure Susceptibility
Authors: Liu Qinghang , Chen Xiongwen , MacDonnell Scott M. , Kranias Evangelia G. , Lorenz John N. , Leitges Michael , Houser Steven R. , Molkentin Jeffery D.
Published: June 2009

Protein kinase (PK)Cα, PKCβ, and PKCγ comprise the conventional PKC isoform subfamily, which is thought to regulate cardiac disease responsiveness. Indeed, mice lacking the gene for
PKC
α show enhanced cardiac contractility and reduced susceptibility to heart failure. Recent data also suggest that inhibition of conventional PKC isoforms with Ro-32-0432 or Ro-31-8220 enhances heart function and antagonizes failure, although the isoform responsible for these effects is unknown. Here, we investigated mice lacking
PKC
α,
PKC
β, and
PKC
γ for effects on cardiac contractility and heart failure susceptibility.
PKC
α
−/−
mice, but not
PKC
βγ
−/−
mice, showed increased cardiac contractility, myocyte cellular contractility, Ca
2+
transients, and sarcoplasmic reticulum Ca
2+
load.
PKCα
−/−
mice were less susceptible to heart failure following long-term pressure-overload stimulation or 4 weeks after myocardial infarction injury, whereas
PKC
βγ
−/−
mice showed more severe failure. Infusion of ruboxistaurin (LY333531), an orally available PKCα/β/γ inhibitor, increased cardiac contractility in wild-type and
PKC
βγ
−/−
mice, but not in
PKC
α
−/−
mice. More importantly, ruboxistaurin prevented death in wild-type mice throughout 10 weeks of pressure-overload stimulation, reduced ventricular dilation, enhanced ventricular performance, reduced fibrosis, and reduced pulmonary edema comparable to or better than metoprolol treatment. Ruboxistaurin was also administered to
PKC
βγ
−/−
mice subjected to pressure overload, resulting in less death and heart failure, implicating PKCα as the primary target of this drug in mitigating heart disease. As an aside,
PKC
αβγ triple-null mice showed no defect in cardiac hypertrophy following pressure-overload stimulation. In conclusion, PKCα functions distinctly from PKCβ and PKCγ in regulating cardiac contractility and heart failure, and broad-acting PKC inhibitors such as ruboxistaurin could represent a novel therapeutic approach in treating human heart failure.
Long-Term Functional Recovery After First Ischemic Stroke
Authors: Dhamoon Mandip S. , Moon Yeseon Park , Paik Myunghee C. , Boden-Albala Bernadette , Rundek Tatjana , Sacco Ralph L. , Elkind Mitchell S.V.
Published: June 2009

Background and Purpose—

Several factors predict functional status after stroke, but most studies have included hospitalized patients with limited follow-up. We hypothesized that patients with ischemic stroke experience functional decline over 5 years independent of recurrent stroke and other risk factors.

Methods—

In the population-based Northern Manhattan Study, patients ≥40 years of age with incident ischemic stroke were prospectively followed using the Barthel Index at 6 months and annually to 5 years. Baseline stroke severity was categorized as mild (National Institutes of Health Stroke Scale <6), moderate (6 to 13), and severe (≥14). Follow-up was censored at death, recurrent stroke, or myocardial infarction. Generalized Estimating Equations provided ORs and 95% CIs for predictors of favorable (Barthel Index ≥95) versus unfavorable (Barthel Index <95) functional status after adjusting for demographic and medical risk factors.

Results—

Of 525 patients, mean age was 68.6±12.4 years, 45.5% were male, 54.7% Hispanic, 54.7% had Medicaid/no insurance, and 35.1% had moderate stroke. The proportion with Barthel Index ≥95 declined over time (OR, 0.91; 95% CI, 0.84 to 0.99). Changes in Barthel Index by insurance status were confirmed by a significant interaction term (β for interaction=−0.167,
P
=0.034); those with Medicaid/no insurance declined (OR, 0.84;
P
=0.003), whereas those with Medicare/private insurance did not (OR, 0.99;
P
=0.92).

Conclusions—

The proportion of patients with functional independence after stroke declines annually for up to 5 years, and these effects are greatest for those with Medicaid or no health insurance. This decline is independent of age, stroke severity, and other predictors of functional decline and occurs even among those without recurrent stroke or myocardial infarction.
Patients Enrolled in Large Randomized Clinical Trials of Antiplatelet Treatment for Prevention After Transient Ischemic Attack or Ischemic Stroke Are Not Representative of Patients in Clinical Practice
Authors: Maasland Lisette , van Oostenbrugge Robert J. , Franke Cees F. , Scholte op Reimer Wilma J.M. , Koudstaal Peter J. , Dippel Diederik W.J.
Published: June 2009

Background and Purpose—

Many randomized clinical trials have evaluated the benefit of long-term use of antiplatelet drugs in reducing the risk of new vascular events in patients with a recent transient ischemic attack or ischemic stroke. Evidence from these trials forms the basis for national and international guidelines for the management of nearly all such patients in clinical practice. However, abundant and strict enrollment criteria may limit the validity and the applicability of results of randomized clinical trials to clinical practice. We estimated the eligibility for participation in landmark trials of antiplatelet drugs of an unselected group of patients with stroke or transient ischemic attack from a national stroke survey.

Methods—

Nine hundred seventy-two patients with transient ischemic attack or ischemic stroke were prospectively and consecutively enrolled in the Netherlands Stroke Survey. We applied 7 large antiplatelet trials’ enrollment criteria.

Results—

In total, 886 patients were discharged alive and available for secondary prevention. Mean follow-up was 2.5 years. The annual rate of transient ischemic attack, stroke, or nonfatal myocardial infarction was 6.7%. The proportions of patients fulfilling the trial enrollment criteria ranged from 25% to 67%. Mortality was significantly higher in ineligible patients (27% to 41%) than in patients fulfilling enrollment criteria (16% to 20%). Rates of vascular events were not higher in trial-eligible patients than in ineligible patients.

Conclusions—

Our data confirm that patients with ischemic attack and stroke enrolled in randomized clinical trials are only partially representative of patients in clinical practice. Use of less strict enrollment criteria could enhance “generalizability” and result in more efficient selection of patients for randomized clinical trials.
M1 Susceptibility Vessel Sign on T2* as a Strong Predictor for No Early Recanalization After IV-t-PA in Acute Ischemic Stroke
Authors: Kimura Kazumi , Iguchi Yasuyuki , Shibazaki Kensaku , Watanabe Masao , Iwanaga Takeshi , Aoki Junya
Published: June 2009

Background and Purpose—

In acute stroke patients treated with intravenous tissue plasminogen activator (t-PA), early recanalization of occluded arteries can improve the clinical outcome. The magnetic susceptibility effect of deoxygenated hemoglobin in red thrombi can present as hypointense signals on T2*-weighted gradient echo imaging. We investigated whether the gradient echo imaging M1 susceptibility vessel sign (M1 SVS) can predict no early recanalization after t-PA infusion.

Methods—

Patients with internal carotid artery and M1 occlusion were prospectively studied. MRI studies, including DWI, T2*, and MRA, were performed before and within 30 minutes and 24 hours after t-PA infusion. The NIHSS score was obtained before and 7 days after t-PA administration. The relationship between the presence of the M1 SVS and no early recanalization and patient outcome was examined.

Results—

A total of 48 patients (29 men; mean age, 74.6±11.2 years) were enrolled. M1 SVS was present in 13 (27.1%) patients and absent in 35 (72.9%) patients. There were no significant differences in clinical characteristics between the 2 groups. Follow-up MRA within 30 minutes after t-PA infusion revealed that 20 (57.1%) of the 35 patients without the M1 SVS had early recanalization, but that none of the 13 patients with the M1 SVS had early recanalization (
P
=0.0002). Seven days after t-PA infusion, dramatic improvement was more frequently observed in patients without the M1 SVS (51.4%) than in those with the M1 SVS (0%,
P
=0.0007).

Conclusion—

The M1 SVS on T2* appears to be a strong predictor for no early recanalization after t-PA therapy.
Large-Cohort Comparison Between Three-Dimensional Time-of-Flight Magnetic Resonance and Rotational Digital Subtraction Angiographies in Intracranial Aneurysm Detection
Authors: Li Ming-Hua , Cheng Ying-Sheng , Li Yong-Dong , Fang Chun , Chen Shi-Wen , Wang Wu , Hu Ding-Jun , Xu Hao-Wen
Published: June 2009

Background and Purpose—

The value of MR angiography varies in diagnosis of intracranial aneurysms due to the difference of equipment and imaging technique. This study was to compare the effectiveness of 3-dimensional time-of-flight MR angiography at 3 T and rotational digital subtraction angiography, both with volume rendering (VR), in detecting intracranial aneurysms.

Methods—

One hundred thirty-eight patients with suspected or known aneurysms and other cerebral vascular diseases detected by MR angiography underwent digital subtraction angiography examinations. Postprocessing techniques, including VR and the single artery highlighting method, were performed by a 3-dimensional specialist. The VR-digital subtraction angiography was obtained as the gold standard.

Results—

The rotational digital subtraction angiography and VR-digital subtraction angiography revealed 146 aneurysms in 122 patients and no aneurysms in 16 patients. Of the 276 vessels examined, 136 vessels had 146 aneurysms and 140 vessels had none. Per vessel and per aneurysm sensitivities were 100%, whereas the per vessel accuracy ranged from 97.5% to 98.6% and the per aneurysm accuracy ranged from 95.1% to 97.0%.

Conclusions—

VR 3-dimensional time-of-flight MR angiography at 3 T has excellent sensitivity, accuracy, and correlation with VR-digital subtraction angiography and is comparable to catheter cerebral angiography for the evaluation of patients with intracranial aneurysms who tolerate MR angiography well.
Plasma and Brain Matrix Metalloproteinase-9 After Acute Focal Cerebral Ischemia in Rats
Authors: Park Kyung-Pil , Rosell Anna , Foerch Christian , Xing Changhong , Kim Woo Jean , Lee Seoul , Opdenakker Ghislain , Furie Karen L. , Lo Eng H.
Published: June 2009

Background and Purpose—

Plasma levels of matrix metalloproteinase-9 (MMP-9) have been proposed to be a useful biomarker for assessing pathological events in brain. Here, we examined the temporal profiles of MMP-9 in blood and brain using a rat model of acute focal cerebral ischemia.

Methods—

Plasma and brain levels of MMP-2 and MMP-9 were quantified at 3, 6, 12, and 24 hours after permanent middle cerebral artery occlusion in male Sprague-Dawley rats. Infarct volumes at 24 hours were confirmed with 2,3,5-triphenyl-tetrazolium-chloride staining.

Results—

In plasma, zymographic bands were detected between 70 and 95 kDa corresponding to pro-MMP-2, pro-MMP-9, and activated MMP-9. A higher 135-kDa band was also seen that is likely to be NGAL-conjugated MMP-9. After ischemia, there were no significant changes in pro-MMP-2, but plasma levels of pro-MMP-9 steadily increased over the course of 24 hours. Activated MMP-9 levels in plasma were significantly elevated only at 24 hours. Plasma NGAL-MMP-9 complexes showed a transient elevation between 3 to 6 hours, after which levels decreased back down to pre-ischemic baselines. In brain homogenates, pro-MMP-2, pro-MMP-9, and activated MMP-9 were seen but no NGAL-MMP-9 bands were detected. Compared to the contralateral hemisphere, MMP-2 and MMP-9 levels in ischemic brain progressively increased over the course of 24 hours. Overall levels of MMP-9 in plasma and brain were significantly correlated, especially at 24 hours. Plasma levels of pro-MMP-9 at 24 hours were correlated with final infarct volumes.

Conclusions—

Elevated plasma levels of MMP-9 appear to be correlated with brain levels within 24 hours of acute cerebral ischemia in rats. Further investigation into clinical profiles of MMP-9 in acute stroke patients may be useful.
Walking After Stroke: What Does Treadmill Training With Body Weight Support Add to Overground Gait Training in Patients Early After Stroke?
Authors: Franceschini Marco , Carda Stefano , Agosti Maurizio , Antenucci Roberto , Malgrati Daniele , Cisari Carlo
Published: June 2009

Background and Purpose—

This study aimed to assess the effectiveness of gait training using body weight support on a treadmill compared with conventional gait training for people with subacute stroke who were unable to walk.

Methods—

This was a single-blind, randomized, controlled trial with a 6-month follow-up. Ninety-seven subjects were recruited within 6 weeks of stroke onset and were randomly assigned to conventional rehabilitative treatment plus gait training with body weight support on a treadmill (experimental group; n=52) and conventional treatment with overground gait training only (control group; n=45). All subjects were treated in 60-minute sessions every weekday for 4 weeks. Outcome measures were Motricity Index, Trunk Control test, Barthel Index, Functional Ambulation Categories, 10-meter and 6-minute Walk Tests, and Walking Handicap Scale. Assessments were made at baseline, after 20 sessions of treatment, 2 weeks after treatment, and 6 months after stroke.

Results—

After treatment, all patients were able to walk. Both groups showed improvement in all outcome measures (
P
<0.0063) at the end of the treatment and at follow-up. No differences were seen between the 2 groups before, during, and after treatment and at follow-up.

Conclusions—

In subacute patients with stroke, gait training on a treadmill with body weight support is feasible and as effective as conventional gait training. However, the need for more personnel for treadmill training makes the use of robotically assisted systems more compelling.
Binge Drinking and Mortality From All Causes and Cerebrovascular Diseases in Korean Men and Women
Authors: Sull Jae Woong , Yi Sang-Wook , Nam Chung Mo , Ohrr Heechoul
Published: June 2009

Background and Purpose—

The purpose of this study was to examine the association between binge drinking and risks of mortality due to all causes of death with a focus on cerebrovascular disease in Korean men and women.

Methods—

This study followed a cohort of 6291 residents in Kangwha County, aged ≥55 years in March 1985, for their cause-specific mortality for 20.8 years up to December 31, 2005. We calculated hazard ratio of mortality by experience or frequency of binge drinking using the Cox proportional hazard model. Binge drinking was defined as having ≥6 drinks on one occasion.

Results—

In men, binge drinkers who drink daily had an increased risk of mortality from all causes (hazard ratio, 1.33; 95% CI, 1.11 to 1.60) as compared with nondrinkers. They showed much increased risks of mortality from total stroke (hazard ratio, 1.86; 95% CI, 1.16 to 2.99) and hemorrhagic stroke (hazard ratio, 3.39; 95% CI, 1.38 to 8.35). Female binge drinkers also showed an increased risk of mortality from cardiovascular disease as compared with female nondrinkers, but the outcome was not statistically significant.

Conclusions—

The results of this study suggest that frequent binge drinking has a harmful effect on hemorrhagic stroke in Korean men. These findings need to be confirmed in further studies.
Ant-Based Computing
Authors: Michael Loizos
Published: June 2009

A biologically and physically plausible model for ants and pheromones is proposed. It is argued that the mechanisms described in this model are sufficiently powerful to reproduce the necessary components of universal computation. The claim is supported by illustrating the feasibility of designing arbitrary logic circuits, showing that the interactions of ants and pheromones lead to the expected behavior, and presenting computer simulation results to verify the circuits' working. The conclusions of this study can be taken as evidence that coherent deterministic and centralized computation can emerge from the collective behavior of simple distributed Markovian processes such as those followed by biological ants, but also, more generally, by artificial agents with limited computational and communication abilities.