bluuebunny/crossref_metadata_2025 huggingface dataset:
The telomerase template antagonist GRN163L alters MDA-MB-231 breast cancer cell morphology, inhibits growth, and augments the effects of paclitaxel
Authors: Goldblatt Erin M. , Gentry Erin R. , Fox Melanie J. , Gryaznov Sergei M. , Shen Changyu , Herbert Brittney-Shea
Published: July 2009

Telomeres are repetitive (TTAGGG)n DNA sequences found at the end of chromosomes that protect the ends from recombination, end to end fusions, and recognition as damaged DNA. Telomerase activity can be detected in 85% to 90% of human tumors, which stabilizes telomeres to prevent apoptosis or cellular senescence. Previous reports showed the efficacy of the novel telomerase template antagonist, GRN163L, as a potential anticancer agent. The objective of the present study was to elucidate the molecular effects of GRN163L in MDA-MB-231 breast cancer cells and to determine whether GRN163L could be used in mechanism-based combination therapy for breast cancer. We observed that GRN163L reduced MDA-MB-231 growth rates without a significant effect on breast cancer cell viability within the first 14 days in vitro. In addition, GRN163L altered cell morphology, actin filament organization, and focal adhesion formation in MDA-MB-231 cells. Importantly, the cellular response to GRN163L significantly augmented the effects of the microtubule stabilizer paclitaxel in MDA-MB-231 breast cancer cell growth in vitro and in vivo compared with paclitaxel alone or a mismatch control oligonucleotide plus paclitaxel. Furthermore, in vitro MDA-MB-231 invasive potential was significantly inhibited with GRN163L and paclitaxel. These data support a rationale for potentially combining GRN163L with paclitaxel for the treatment of breast cancer in the clinical setting. [Mol Cancer Ther 2009;8(7):2027–35]
Preclinical evaluation of a novel pyrimidopyrimidine for the prevention of nucleoside and nucleobase reversal of antifolate cytotoxicity
Authors: Thomas Huw D. , Saravanan Kappusamy , Wang Lan-Zhen , Lin Mei-Ju , Northen Julian S. , Barlow Hannah , Barton Marion , Newell David R. , Griffin Roger J. , Golding Bernard T. , Curtin Nicola J.
Published: July 2009

Antifolates have been used to treat cancer for the last 50 years and remain the mainstay of many therapeutic regimes. Nucleoside salvage, which depends on plasma membrane transport, can compromise the activity of antifolates. The cardiovascular drug dipyridamole inhibits nucleoside transport and enhances antifolate cytotoxicity in vitro, but its clinical activity is compromised by binding to the plasma protein α1-acid glycoprotein (AGP). We report the development of a novel pyrimidopyrimidine analogue of dipyridamole, NU3153, which has equivalent potency to dipyridamole, remains active in the presence of physiologic levels of AGP, inhibits thymidine incorporation into DNA, and prevents thymidine and hypoxanthine rescue from the multitargeted antifolate, pemetrexed. Pharmacokinetic evaluation of NU3153 suggested that a soluble prodrug would improve the in vivo activity. The valine prodrug of NU3153, NU3166, rapidly broke down to NU3153 in vitro and in vivo. Plasma NU3153 concentrations commensurate with rescue inhibition in vitro were maintained for at least 16 hours following administration of NU3166 to mice at 120 mg/kg. However, maximum inhibition of thymidine incorporation into tumors was only 50%, which was insufficient to enhance pemetrexed antitumor activity in vivo. Comparison with the cell-based studies revealed that pemetrexed enhancement requires substantial (≥90%) and durable inhibition of nucleoside transport. In conclusion, we have developed non-AGP binding nucleoside transport inhibitors. Pharmacologically active concentrations of the inhibitors can be achieved in vivo using prodrug approaches, but greater potency is required to evaluate inhibition of nucleoside rescue as a therapeutic maneuver. [Mol Cancer Ther 2009;8(7):1828–37]
Alaninaminotransferase (ALAT, GPT): Eine Neubewertung der Ausschlußgrenzen für Blutspender
Authors: Grunenberg R. , Banik N. , Krüger J.
Published: July 2009

Hintergrund: Die Wertigkeit der Alaninaminotransferase (ALAT)-Testung bei Blutspendern und der in den Richtlinien empfohlene Ausschlußwert sind umstritten. Diese Arbeit soil unter Berücksichtigung der neuen Standardmethoden zur Bestimmung von Enzymaktivitäten, die eine Meßtemperatur von 37 °C vorsehen, die Häufigkeitsverteilung der ALAT-Aktivitäten in einem Blutspenderkollektiv doku-mentieren, praktikable Ausschlußwerte bestimmen und die Ursachen erhöhter ALAT-Werte aufdecken. Material und Methoden: Bei 5706 Blutspendern wurden mit dem Reflotron®-System die ALAT-Aktivitäten bei 37 °C bestimmt. Spender mit ALAT-Werten über 51 IU/1 wurden zurückgestellt, und es wurde eine weiterführende Diagnostik angeschlossen. Ergebnisse: Durch Logarithmierung der ALAT-Aktivitäten in einem Blutspenderkollektiv wurde annähernd eine Normalverteilung erreicht. Der Mittelwert der logarithmierten Werte wurde bei weiblichen Spendern mit 1,24 ± 0,14, bei männlichen mit 1,35 + 0,16 ermittelt (entspricht mittleren Aktivitäten von 17,6 bzw. 22,5 IU/1). Bei einem Cutoff > 33,4 IU/1 für Frauen bzw. > 46,7 IU/1 für Manner (geometrischer Mittelwert +2,0 Standardabweichung, SD) müßten 2,8 bzw. 2,7%, bei Werten > 39,1 bzw. 56,1 IU/1 (geometrischer Mittelwert +2,5 SD) 1,8 bzw. 1,4% zurückgestellt werden. Vermutete Ursachen erhöhter ALAT-Aktivitäten bei 166 Spendern waren erhöhter Alkoholkonsum (82), Infekte mit oder ohne Antibiotikatherapie (29), Einnahme hepatotoxischer Medikamente (8), extreme sport -liche Leistungen (5), Bodybuilding unter Anabolikaeinnahme (2), akute HCV- (1), HBV- (1), CMV-Infektion (1), Alkohol-/Drogenabhängigkeit mit Nachweis von HCV-Antikörpern (1). Schlußfolgerungen: Das ALAT-Spenderscreening ist eine wichtige Ergänzung zu den serologischen Pflichtuntersuchungen, jedoch müssen die Grenzwerte ge-schlechtspezifisch angepaßt werden. Der gegenwärtig in den Richtlinien empfohlene Cutoff-Wert von > 45 IU/1 (25 °C), analog > 81,8 IU/1 (37 °C), ist zu hoch angesetzt, denn er würde Frauen erst mit Aktivitäten größer als die 4,5fache SD (etwa 0,2%), Manner mit Aktivitäten größer als die 3,5fache SD (etwa 0,3%) vom geometrischen Mittelwert ausschließen.
Discordance in Human Paraoxonase-1 Gene between Phenotypes and Genotypes in Chronic Kidney Disease
Authors: Paragh Gyorgy , Seres Ildiko , Harangi Mariann , Pocsai Zsuzsa , Asztalos Laszlo , Locsey Lajos , Szeles Gyorgy , Kardos Laszlo , Varga Eva , Karpati Istvan , Adany Roza
Published: July 2009

Background: Human serum paraoxonase-1 (PON1) is a high-density lipoprotein-associated ester hydrolase which can inhibit low-density lipoprotein oxidation and has an antiatherogenic effect. Two common polymorphisms are known in the PON1 gene in humans (at positions 55 and 192), from which the latter gene alteration has been mainly attributed to alter the activity of the protein. Moreover, significantly reduced PON1 activity was found in chronic kidney disease (CKD) and renal transplant patients. Methods: The aim of the present study was to investigate the genotype and phenotype distribution of the PON1 gene as well as its end product activity in patients with CKD (n = 117), in renal transplant recipients (n = 146) and in reference subjects (n = 1,180). Results: Unexpectedly high discordances between phenotype and genotype assessments were observed in all studied groups (28.2% in the CKD, 20.55% in the transplant and 30.9% in the reference group). Arylesterase activity was significantly lower in the CKD group compared to the reference sample. There were no significant differences between patients and the reference group in the frequencies of polymorphisms PON1–55 and PON1–192. PON1 activity did not differ in patients compared to the reference group. Conclusions: Both PON1 phenotype and genotype determinations are necessary to estimate PON1 status.
Clinical Significance of Posterior Circulation Changes after Revascularization in Patients with Moyamoya Disease
Authors: Huang Abel Po-Hao , Liu Hon-Man , Lai Dar-Ming , Yang Chi-Cheng , Tsai Yi-Hsin , Wang Kuo-Chuan , Yang Shih-Hung , Kuo Meng-Fai , Tu Yong-Kwang
Published: July 2009

Objective: It has been noted that the posterior circulation serves as an important source of collateral blood supply in moyamoya disease. Since most of the literature has focused on non-operative cases and many symptomatic patients receive surgical revascularization, we evaluated the posterior circulation changes after revascularization and found that progressive posterior cerebral artery (PCA) steno-occlusive changes after revascularization caused cerebral hemodynamic compromise and clinical deterioration in a significant portion of patients. Methods: Twenty-three moyamoya disease patients with ischemic presentation who received revascularization with complete angiography and xenon CT during a minimum of 3 years’ clinical follow-up were enrolled. Revascularization was performed in 38 hemispheres. Pre- and postoperative angiography were reviewed to determine the internal carotid artery (ICA) stage, PCA stage, leptomeningeal collateral (LMC) grade, and Matsushima synangiosis grade. The postoperative regional cerebral blood flow (CBF) and cerebral vascular reserve (CVR) were recorded and correlated with angiographic findings and clinical outcome. Results: Progression of ICA staging was noted in 23 sides (55.2%), and progression of PCA staging was noted in 18 sides (47.4%). Among the 18 cases of PCA stage progression, an associated decrease in LMC grade was noted in 12 sides (66.7%). These changes were associated with decreased regional CBF and CVR, which also explained the recurrent ischemic symptoms in 27.8% of these patients. In contrast, LMC grade increased in 15 (65.2%) sides of patients with ICA progression. Conclusions: Progressive steno-occlusive change in the PCA after revascularization is associated with a reduction in LMC blood flow and cerebral ischemia in moyamoya patients. This phenomenon might cause recurrent ischemic symptoms in 27.8% of patients.
Analytical Review of the Evidence for Renoprotection by Renin-Angiotensin-Aldosterone System Blockade in Chronic Kidney Disease – A Call for Caution
Authors: Onuigbo Macaulay A.
Published: July 2009

Despite reported renoprotection with angiotensin-converting enzyme inhibitors (ACEIs)/angiotensin receptor blockers (ARBs), and notwithstanding their increased use, we continue to experience an epidemic of acute renal failure (ARF)/chronic kidney disease/end-stage renal disease. Consequently, concerns about iatrogenic renal failure have resurfaced. Different analysis of these trials revealed flaws such as recruitment of relatively younger patients with preserved baseline renal function, common utilization of lower end doses of ACEIs/ARBs, high drug discontinuation rates, excessive use of surrogate endpoints, inadequate reporting of adverse effects, and short duration studies. Again, lower 24-hour ambulatory blood pressure among patients in the ramipril arm of the micro-HOPE (Heart Outcomes Prevention Evaluation) study raises doubts of renoprotection beyond blood pressure lowering. The disappointing results from the ONTARGET (Ongoing Telmisartan Alone and in Combination with Ramipril Global Endpoint Trial) study only compounded these doubts. We demonstrated significant renal salvage after ACEI/ARB was discontinued in chronic kidney disease patients recruited with increasing ARF while on ACEI/ARB. Apart from our reports, there are increasing reports incriminating the use of ACEI/ARB with ARF exacerbations. We conclude that close and indefinite monitoring of estimated glomerular filtration rate is an absolute must in these patients. The treating physician must be ready to consider trial discontinuation of ACEI/ARB, promptly. Combination ACEI + ARB therapy should be the exception, rather than the rule. Temporary withdrawal of ACEI/ARB before certain exposures, ‘renoprevention’, would only further improve the results of renoprotection.
Increased Aortic Wall Stiffness Associated with Low Circulating Fetuin A and High C-Reactive Protein in Predialysis Patients
Authors: Porażko Tomasz , Kuźniar Jakub , Kusztal Mariusz , Kuźniar Tomasz J. , Weyde Wacław , Kuriata-Kordek Magdalena , Klinger Marian
Published: July 2009

Background/Aims: Vascular calcification and arterial stiffening are cardiovascular risk factors among chronic kidney disease (CKD) patients. The aim of the study was to analyze relationships between inflammatory markers, fetuin A and arterial wall stiffness in CKD patients in the predialysis period and on maintenance dialysis. Methods: Serum C-reactive protein (hs-CRP), fetuin A, interleukin 6 (IL-6) and other classical markers of atherosclerosis were measured in a group of 155 CKD patients (77 on hemodialysis, HD, 29 on peritoneal dialysis, 49 in CKD stage 5 in the predialysis period) and in 30 healthy volunteers. The aortic pulse wave velocity (aoPWV) was recorded using a tonometric method. Results: The aoPWV, serum hs-CRP and IL-6 were higher and fetuin A levels were lower in all CKD groups than in controls. In multiple regression analysis, the age appeared as the strongest, independent factor increasing arterial wall stiffness in all investigated groups, including controls, whereas the association of aoPWV with IL-6 and fetuin A remained significant only in HD patients. Conclusions: Aortic wall stiffness is higher in CKD patients than in controls, and it already develops in the predialysis period. Age is the principal determinant of arterial wall stiffness also in CKD patients. The acceleration of arterial wall stiffness in CKD is associated with additional factors, i.e. fetuin A deficiency and higher CRP and IL-6.
Comparison of Extracellular Volume and Blood Pressure in Hemodialysis and Peritoneal Dialysis Patients
Authors: Chen Yi-Chou , Lin Cheng-Jui , Wu Chih-Jen , Chen Han-Hsiang , Yeh Jui-Chi
Published: July 2009

Background: Extracellular volume (ECV) assessment by bioimpedance analysis is a reliable technique for determining post dialysis target weight. Overhydration and dehydration are two points of dialysis patients’ fluid status and both affect blood pressure. We compared ECV and blood pressure between hemodialysis and peritoneal dialysis patients. Methods: We studied ECV of 74 (38 females and 36 males) normal subjects, 121 (63 females and 58 males) stable chronic hemodialysis and 84 (57 females and 27 males) stable chronic peritoneal dialysis patients. ECV as a percentage of body weight was designated ECV%. An ECV% over 28% in male patients and over 25% in females was defined as overhydration according to the 100th percentile of normal subjects. An ECV% below 21% in male patients and below 18% in females was defined as dehydration. Hypertension was defined as systolic blood pressure >140 mm Hg or diastolic blood pressure >90 mm Hg. Results: In male and female hypertension and normotension, the ECV% of peritoneal dialysis patients was significantly higher than that of hemodialysis patients (all p < 0.0001). The overhydration frequency of peritoneal dialysis patients was significantly higher than that of hemodialysis patients (p < 0.0001). The dehydration frequency of peritoneal dialysis patients was significantly less than that of hemodialysis patients (p < 0.01). The proportion of hypertension in peritoneal dialysis patients was higher than that in hemodialysis patients, but with no significant difference (p = 0.085). All male and female patients with overhydration had hypertension in either the hemodialysis or peritoneal dialysis group. Patients with dehydration usually had normotension, but some of them had hypertension. Conclusions: (1) Overhydration and hypertension are more common in peritoneal dialysis patients than in hemodialysis patients. (2) Dehydration is noticed in hemodialysis patients, but not in peritoneal dialysis patients.
Hepatic Iron, Serum Ferritin, HFE Mutation, and Hepatic Fibrosis in Chronic Hepatitis C
Authors: Won Ji-Eon , Jeong Sook-Hyang , Chung Jae Il , Lee Ji Hye , Hwang Sung Ho , Kim Jin-Wook , Lee Sang Hyub , Kim Nayoung , Park Young Soo , Lee Dong Ho , Kim Haeryoung
Published: July 2009

Objectives: We studied the status of hepatic iron deposition and its relationship with blood iron indices, liver histology, and HFE gene mutations in Korean patients with chronic hepatitis C (CH-C). Methods: 105 patients with CH-C who underwent pretreatment liver biopsy were consecutively enrolled. The hepatic iron deposition, histological activity and fibrosis were assessed by appropriate pathological scoring systems, clinical data including serum iron indices, and HFE gene mutation. Results: Hepatic iron deposition was found in 37 patients (35%), which was not significantly associated with degree of hepatic fibrosis or steatosis. The serum ferritin level was elevated in 27% of the patients and was an independent factor associated with hepatic iron deposition by logistic regression; however, it was not significantly associated with hepatic fibrosis either. Only H63D heterozygote was found in 6 out of 48 patients (12.5%), which was not different from the prevalence of H63D mutation in the Korean population (8.5%). Conclusions: Hepatic iron deposition was uncommon and mild in Korean CH-C. Neither hepatic iron deposition nor serum ferritin were significantly related to the severity of hepatic fibrosis, which does not support the significant role of iron in the progression of hepatic fibrosis.
Insight and Obsessive-Compulsive Disorder: A Conceptual Analysis
Authors: Marková Ivana S. , Jaafari Nemat , Berrios German E.
Published: July 2009

Analysis of insight in obsessive-compulsive disorders (OCD) raises conceptual problems that need addressing before meaningful empirical work can be undertaken. Insight and OCD are locked within a definitional contradiction relevant both to the nosological boundaries of OCD and the meaning of insight itself. Given that it is a form of self-knowledge, it is proposed here that insight is best conceived as a mental state rather than symptom or symptom-dimension. As an aspect of this mental state, the clinical phenomenon of insight should be understood as independent of any underlying disease albeit influenced by it and by other factors. As the focus of empirical research, the phenomenon of insight is dependent on the concept of insight, the measure by which it is assessed and on the ‘object’ of insight assessment. Explication of these factors allows for the delineation of specific insight phenomena whose respective usefulness can be determined by empirical research.
The Diagnoses of Schizophrenia, Schizoaffective Disorder, Bipolar Disorder and Unipolar Depression: Interrater Reliability and Congruence between DSM-IV and ICD-10
Authors: Cheniaux Elie , Landeira-Fernandez J. , Versiani Marcio
Published: July 2009

Background: The present study investigated the interrater reliability of the diagnoses of schizophrenia (SCH), schizoaffective disorder (SAD), bipolar disorder (BPD) and unipolar depression (UPD) according to both DSM-IV and ICD-10, as well as the diagnostic congruence between the two classificatory systems. Sampling and Methods: Using the Composite International Diagnostic Interview, two trained psychiatrists simultaneously evaluated 100 inpatients and independently assessed the psychiatric diagnoses. The Cohen’s kappa coefficient was employed to estimate interrater reliability and diagnostic congruence between DSM-IV and ICD-10. Results: SCH was more frequent according to ICD-10 than DSM-IV criteria. Considering both diagnostic systems, all the four nosological categories, but ICD-10 SAD and DSM-IV UPD, were associated with interrater reliability coefficients above 0.50. The coefficient of the diagnostic congruence between DSM-IV and ICD-10 was inferior to 0.50 only for SAD. BPD was associated with the highest degrees of both interrater reliability and diagnostic congruence. Conclusions: The lack of an item excluding the occurrence of an affective syndrome among ICD-10 diagnostic criteria for SCH can account for: the larger frequency of SCH according to ICD-10 than DSM-IV; the unsatisfactory interrater reliability for the diagnosis of ICD-10 SAD, and the low diagnostic congruence for SAD.
Preoperative Predictors for Improvement after Surgical Untethering in Occult Tight Filum Terminale Syndrome
Authors: Fabiano Andrew J. , Khan Mohammed F. , Rozzelle Curtis J. , Li Veetai
Published: July 2009

Background/Aims: An occult tight filum terminale syndrome has been described wherein clinical symptoms result from tension on the spinal cord despite nondiagnostic spinal magnetic resonance imaging (MRI). Recent reports have suggested a role for surgical untethering in this patient population; however, controversy remains regarding the surgical treatment of this condition. Owing to the various clinical presentations, the relationship of presenting signs and symptoms to postoperative outcomes might be useful in surgical selection. Methods: A retrospective review was conducted of 22 pediatric cases of surgical untethering for suspected occult tight filum terminale syndrome. All patients had nondiagnostic MRI findings, defined as a conus medullaris above the L3 vertebral body and a filum terminale diameter of less than 2 mm. Preoperative symptoms, signs and urodynamic test results were collected and compared with surgical outcomes determined by clinical notes and postoperative urodynamics reports. Abnormal findings on presentation were categorized as dermatologic, urologic, orthopedic and neurologic. Results: Patient age ranged from 7 months to 17 years, and 12 were female. Sixteen (73%) patients experienced subjective and/or objective improvement following surgical untethering. Fourteen patients had abnormal preoperative urodynamic testing, of which 12 underwent postoperative urodynamic testing. Five of these 12 (42%) demonstrated objective improvement postoperatively. Patients presenting with abnormal findings in at least 2 categories were more likely to improve following untethering (88%) than those with abnormalities in only 1 category (20%; p = 0.009). Conclusion: Spinal cord untethering is a treatment option for occult tight filum terminale syndrome. Further evaluation of the relationship between preoperative findings and surgical outcomes may facilitate the selection of surgical candidates.
Indications for Brain Computed Tomography and Hospital Admission in Pediatric Patients with Minor Head Injury: How Much Can We Rely upon Clinical Findings?
Authors: Güzel Ahmet , Hiçdönmez Tufan , Temizöz Osman , Aksu Burhan , Aylanç Hakan , Karasalihoglu Serap
Published: July 2009

Objectives: The aim of this study was to describe the characteristics of patients with a minor head injury (MHI) who were admitted to a pediatric emergency unit and to identify the clinical signs and symptoms that most reliably predict the need for cranial computed tomography (CCT) and hospital admission following MHI. Methods: All patients were retrospectively evaluated according to age, gender, details of injury, presenting symptoms, physical examination findings, radiological investigations ordered and results, length of stay, outcome of the injury and hospitalization rates. Results: The factors affecting indications for computed tomography and hospitalization were retrospectively analyzed in 916 patients – 585 males and 331 females, aged between 1 month and 15 years (mean: 5.01 ± 3.58 years), with MHI. A multivariate analysis revealed significant correlations between CCT abnormalities and Glasgow Coma Scale scores of 13 or 14, headache, posttraumatic amnesia, blurred vision, cephalohematomas, periorbital ecchymoses, otorrhea and abnormal neurological findings. CCT abnormalities were identified in 67 (19.8%) of the 338 CCT scans. Twenty of the 67 patients (29.9%) with CCT scan abnormality had no clinical signs. Of all cases, 125 (13.6%) were hospitalized, 617 (67.4%) were treated as outpatients, and 174 (19.0%) left the emergency department based on a personal decision. Conclusion: Some clinical risk factors can be used as predictors of abnormalities in CCT scans following MHI, but the absence of such clinical findings does not exclude the possibility of intracranial injuries.
Haemophilus influenzae and Streptococcus pneumoniae Infections in Children with Cerebrospinal Fluid Shunts
Authors: Shurtleff D.B. , Loeser J.D. , Avellino A.M. , Duguay S. , Englund J.A. , Marcuse E.K. , Peterson D.
Published: July 2009

Objective: This paper reviews the frequency of central nervous system infections due to Haemophilus influenzae and Streptococcus pneumoniae associated with cerebrospinal fluid (CSF) shunts in pediatric patients. The need for immunizations in this patient population is also evaluated. Patients: All patients with cerebrospinal fluid shunts except those with brain tumors seen in our clinics. Methods: We reviewed data in three computer databases, kept prospectively recording details of CSF shunt procedures and CSF shunt-related infections. Results: 1,226 patients underwent 3,889 shunt placements between 1957 and 2007. Twelve patients had 14 episodes of Haemophilus or pneumococcal infections. Conclusions: Children with CSF shunts are at high risk for infection with H. influenzae and S. pneumoniae. Routine immunizations during infancy in addition to the 23-valent polysaccharide pneumococcal vaccine should be highly and actively encouraged by health care providers caring for children with CSF shunts. Additional expanded-coverage vaccines should be utilized if and when they become available.
Posterior Cerebral Artery Infarction: Diffusion-Weighted MRI Analysis of 205 Patients
Authors: Lee Eugene , Kang Dong-Wha , Kwon Sun U. , Kim Jong S.
Published: July 2009

Background and Purpose: Although cardiac embolism has been shown to be the leading stroke mechanism of posterior cerebral artery (PCA) territory infarction, intrinsic PCA atherosclerotic disease may play a more important role in regions where intracranial diseases are prevalent. We aimed to assess the etiologies and stroke pattern of PCA territory infarction in a Korean population. Method: We reviewed consecutive patients with acute PCA territory infarction who underwent diffusion-weighted MRI (DWI) and magnetic resonance angiography (MRA) within 7 days after onset. Results: A total of 205 patients (male 56%, mean age 65.4 ± 12.4 years) were recruited. ‘Superficial’, ‘deep’ and ‘superficial plus deep’ infarcts accounted for 26.3, 47.8 and 25.9% of infarcts, respectively. There were 126 patients who had infarcts limited to the PCA territory, whereas 79 patients had concomitant infarcts in other territories. Large artery atherosclerosis (LAA, 42.4%) was the most frequent etiology, followed by cardiogenic embolism (20%), small-vessel occlusion (20%), undetermined (18%) and other determined (3%) etiology. Among the 87 patients with LAA, 38 had intrinsic PCA disease without atherosclerosis in the proximal vessels. In these patients, stroke mechanisms included atheromatous branch occlusion (n = 19), in situ thrombotic occlusion (n = 11) and artery-to-artery embolism (n = 8). While the occipital area was the most frequently involved in general, the ventrolateral thalamic area was more frequently involved than the occipital area in patients with intrinsic PCA atherosclerotic disease. Conclusion: The patterns of PCA territory infarction are different according to underlying etiologies. In our population, intrinsic atherosclerotic disease is a relatively important cause of PCA territory infarction that produces strokes through a variety of mechanisms.
T2*-Weighted MRI versus Oxygen Extraction Fraction PET in Acute Stroke
Authors: Donswijk M.L. , Jones P.S. , Guadagno J.V. , Carpenter T.A. , Moustafa R.R. , Fryer T.D. , Aigbirhio F.I. , Warburton E.A. , Baron J.C.
Published: July 2009

Background: Mapping high oxygen extraction fraction (OEF) in acute stroke is of considerable interest to depict the at-risk tissue. Being sensitive to deoxyhemoglobin, T2*-weighted MRI has been suggested as a potential marker of high OEF. Methods: We compared T2*-weighted images from pre-contrast arrival perfusion scans against quantitative positron emission tomography in 5 patients studied 7–21 h after onset of carotid territory stroke. OEF and T2* signal were obtained in the voxels with significantly high OEF. Results: All patients showed increased OEF. No significant relationship between OEF and T2*-weighted signal was found either within or between subjects. Conclusion: We found no indication that T2*-weighted MRI in the way implemented in this investigation was sensitive to high OEF in acute stroke.
Correlation of Diffusion Tensor Imaging with Histology in the Developing Human Frontal Cerebrum
Authors: Trivedi Richa , Husain Nuzhat , Rathore Ram K.S. , Saksena Sona , Srivastava Savita , Malik Gyanendra K. , Das Vinita , Pradhan Mandakini , Pandey Chandra M. , Gupta Rakesh K.
Published: July 2009

Transient early cerebral laminar organization resulting from normal developmental events has been revealed in human beings through histology and imaging studies. DTI studies have postulated that the fractional anisotropy (FA)-based differentiation of different laminar structures reflects both differing cellular density over the glial fibers and fiber alignment in respective regions. The aim of this study was to correlate FA values in these transient zones with histology. Brain DTI was performed on 50 freshly aborted human fetuses with gestational ages (GA) ranging from 12 to 42 weeks. Regions of interest were placed on the cortical plate, subplate, intermediate and germinal matrix (GMx) zones of the frontal lobe to quantify FA values. Glial fibrillary acidic protein (GFAP), neurofilament (NF) and neuron-specific enolase (NSE) immunohistochemical analyses were performed for the cortical plate, intermediate zone and GMx. In the cortical plate, a significant positive correlation was observed between FA values and percentage area of GFAP expression in fetuses ≤28 weeks of GA (r = 0.56, p = 0.01). FA values showed a significant positive correlation with the percentage area of NF expression in the intermediate zone (r = 0.54, p = 0.05). A significant positive correlation was also observed between FA and the number of NSE-positive cells per mm2 in the GMx (r = 0.76, p < 0.01) and subplate (r = 0.59, p = 0.03) zones. The results of our study suggest that the FA can be used as noninvasive marker of neurodevelopmental events in the frontal lobe of human fetal brain.
Active Adaptation of the Tethered Mitral Valve
Authors: Dal-Bianco Jacob P. , Aikawa Elena , Bischoff Joyce , Guerrero J. Luis , Handschumacher Mark D. , Sullivan Suzanne , Johnson Benjamin , Titus James S. , Iwamoto Yoshiko , Wylie-Sears Jill , Levine Robert A. , Carpentier Alain
Published: July 2009

Background—

In patients with left ventricular infarction or dilatation, leaflet tethering by displaced papillary muscles frequently induces mitral regurgitation, which doubles mortality. Little is known about the biological potential of the mitral valve (MV) to compensate for ventricular remodeling. We tested the hypothesis that MV leaflet surface area increases over time with mechanical stretch created by papillary muscle displacement through cell activation, not passive stretching.

Methods and Results—

Under cardiopulmonary bypass, the papillary muscle tips in 6 adult sheep were retracted apically short of producing mitral regurgitation to replicate tethering without confounding myocardial infarction or turbulence. Diastolic leaflet area was quantified by 3-dimensional echocardiography over 61±6 days compared with 6 unstretched sheep MVs. Total diastolic leaflet area increased by 2.4±1.3 cm
2
(17±10%) from 14.3±1.9 to 16.7±1.9 cm
2
(
P
=0.006) with stretch with no change in the unstretched valves despite sham open heart surgery. Stretched MVs were 2.8 times thicker than normal (1.18±0.14 versus 0.42±0.14 mm;
P
<0.0001) at 60 days with an increased spongiosa layer. Endothelial cells (CD31
+
) coexpressing α-smooth muscle actin were significantly more common by fluorescent cell sorting in tethered versus normal leaflets (41±19% versus 9±5%;
P
=0.02), indicating endothelial-mesenchymal transdifferentiation. α-Smooth muscle actin–positive cells appeared in the atrial endothelium, penetrating into the interstitium, with increased collagen deposition. Thickened chordae showed endothelial and subendothelial α-smooth muscle actin. Endothelial-mesenchymal transdifferentiation capacity also was demonstrated in cultured MV endothelial cells.

Conclusions—

Mechanical stresses imposed by papillary muscle tethering increase MV leaflet area and thickness, with cellular changes suggesting reactivated embryonic developmental pathways. Understanding such actively adaptive mechanisms can potentially provide therapeutic opportunities to augment MV area and reduce ischemic mitral regurgitation.
Risk in International Politics
Authors: Stone Randall W.
Published: July 2009

Representative governments under-invest in public goods that provide insurance against risk, The combination of inequality and risk aversion guarantees that the payoffs to insurance are skewed, so the median voter prefers a sub-optimally low level of investment. The problem is exacerbated by supermajority requirements or the need for international coordination. This accounts for some of the characteristic shortcomings of domestic public policy and represents an important obstacle to international cooperation. The argument is illustrated with reference to the Kyoto Protocol and the International Monetary Fund. The argument implies that delegation to international organizations with risk-averse preferences may be welfare enhancing.
Institutional Resilience Amid Political Change: The Case of Biodiversity Conservation
Authors: Steinberg Paul F.
Published: July 2009

There is a substantial literature documenting the spatial mismatch between the geographic location of biological resources and the spatial jurisdiction of the institutions responsible for their management. But little attention has been paid to the disjuncture in temporal scales between the long-term requirements of biodiversity conservation and the short time horizons governing public and private decisions affecting the survival of species and ecosystems. How can we create socially agreed-upon rules governing the long-term use and conservation of biodiversity when ongoing change is one of the defining characteristics of modern society? This article describes a new approach to biodiversity conservation—conservation systems—that addresses this question by providing design criteria that can be used to construct resilient social safety nets for biological diversity.
Kinship, Ethnic Segregation and Multiculturalism in Singapore: A Relational Study
Authors: Chua Vincent
Published: July 2009

The question of inter-ethnic integration and segregation in multicultural societies has been characterised by remarkable tensions at the level of public and scholarly debate between optimists who see 'good' inter-ethnic relations and pessimists who see 'bad' ones. In reality, the ethnic situation in multicultural societies is often more nuanced than these labels suggest. Using personal network analysis applied to a segment of Singapore society, I show that estimates of interethnic contact are highly-contingent upon a range of methodological and social factors. Substantively, I discuss how inter-ethnic interactions may often be hampered by in-group pressures arising from kinship relations. In practice, where 'keeping family' often means 'keeping ethnicity', kinship pre-eminence in everyday life tends to suppress inter-ethnic friendship in intimate regions of personal networks. By contrast, inter-ethnic integration is more readily seen in outer regions of personal networks, suggesting that 'multiculturalism' is, in practice, a form of society based on weak ties rather than strong bonds.
The Choking Game and YouTube: A Dangerous Combination
Authors: Linkletter Martha , Gordon Kevin , Dooley Joe
Published: July 2009

Purpose: To study postings of partial asphyxiation by adolescents on YouTube and to increase awareness of this dangerous activity as well as the value of YouTube as a research tool. Methods: Videos were searched on YouTube using many terms for recreational partial asphyxiation. Data were gathered on the participants and on the occurrence of hypoxic seizure. Results: Sixty-five videos of the asphyxiation game were identified. Most (90%) participants were male. A variety of techniques were used. Hypoxic seizures were witnessed in 55% of videos, but occurred in 88% of videos that employed the “sleeper hold” technique. The videos were collectively viewed 173550 times on YouTube. Conclusions: YouTube has enabled millions of young people to watch videos of the “choking game” and other dangerous activities. Seeing videos may normalize the behavior among adolescents. Increased awareness of this activity may prevent some youths from participating and potentially harming themselves or others.
“Don’t Let Them Die in Vain”
Authors: Boettcher William A. , Cobb Michael D.
Published: July 2009

This article builds on past framing research to probe the impact of casualty frames on the public’s willingness to expend additional “blood and treasure” in an ongoing war. The rhetoric of “sunk costs” (often described as “sacrifices”) that must be redeemed through further conflict is a well-known, yet irrational, trope. Utilizing an experiment embedded in a nationally representative survey on attitudes about Iraq, we find that “investment frames” increase support for the war among individuals who believe the U.S. “did the right thing in Iraq,” but decrease support for the war among those who feel the U.S. “should have stayed out.” We also find, however, that framing effects are inconsistent when the frames are attributed to sources. These latter results demonstrate the importance of including unattributed frames to evaluate source effects in framing research.
Still Not Pushing Back
Authors: Howorth Jolyon , Menon Anand
Published: July 2009

A recent wave of scholarly literature has argued forcibly that the European Union’s European Security and Defence Policy (ESDP) represents an attempt on the part of the EU to “balance” against the United States. According to such analyses, the EU is reacting to American global preeminence by building up its military capacities to enhance its own ability to play a significant, autonomous role in international affairs. This article takes issue with such claims. It points, first, to significant theoretical and methodological shortcomings inherent in the work of the “soft balancers.” Second, and more fundamentally, it subjects this work to careful empirical scrutiny and illustrates how the soft balancers have fundamentally misunderstood ESDP. Finally, it illustrates how such misinterpretations result from a failure to appreciate the profound impact that institutional structures wield over substantive outcomes in international security affairs.
The Impact of Juvenile Inmates’ Perceptions and Facility Characteristics on Victimization in Juvenile Correctional Facilities
Authors: Kupchik Aaron , Snyder R. Bradley
Published: July 2009

In this study, the authors analyze data on juvenile correctional facilities from the Performance-based Standards for Youth Correction and Detention Facilities project to predict victimization and fear among individual juvenile inmates. The authors estimate multilevel models using both facility and individual level factors. Their results depart from prior research efforts, which have focused primarily on either an importation or a deprivation model for explaining facility misconduct. In contrast, the authors find evidence of a third model that merges individual- and facility-level variables to consider individual youth’s perceptions of facility rules and practices. They find that the best predictors of victimization are youths’ understanding of facility rules as well as their perceptions of school quality and staff helpfulness.
Correlates of Heavy Smoking Among Alcohol-Using Methadone Maintenance Clients
Authors: Nyamathi Adeline M. , Sinha Karabi , Marfisee Mary , Cohen Allan , Greengold Barbara , Leake Barbara
Published: July 2009

This cross-sectional study examines predictors of heavy smoking among 256 male and female methadone maintenance therapy (MMT) clients from five MMT clinics in the Los Angeles area. The authors find that women report lower rates of heavy smoking than men (47% vs. 54%, respectively), in concordance with current literature pointing to gender differences in smoking behaviors. In particular, men who report heavy drinking, fair or poor health, and recent heroin use are more likely to report heavy smoking compared with men not reporting these factors. Women who report recent heroin use, a lifetime history of sex trade, and who have been ill enough to require a blood transfusion also have greater odds of reporting heavy cigarette smoking. Findings from this study may aid not only in designing gender-based smoking cessation programs for MMT clients but also in addressing the gender-based issues related to smoking in such a population.
Origins of the Problem of Health-related Behaviours
Authors: Armstrong David
Published: July 2009

In recent years a number of public health, prevention and disease management strategies have emerged that depend on changing health-related behaviours. The definition of those behaviours, indeed of the very idea of behaviour, remains unchallenged in these initiatives, as behaviour is a taken-for-granted concept. Yet the idea of a changeable behaviour is a relatively recent phenomenon and the aim of this paper is to map its emergence and transformation over the last century. Its origins are shown to lie in the first half of the 20th century when it was derived from the ideas of conduct and movement. From mid-century onwards, it has been increasingly construed as being underpinned by a sense of agency and as a legitimate target for healthcare interventions. Finally, in the 21st century it has become stabilized as a core dimension of health and illness.
Social Inequalities in Grip Strength, Physical Function, and Falls Among Community Dwelling Older Men and Women
Authors: Syddall Holly , Evandrou Maria , Cooper Cyrus , Aihie Sayer Avan
Published: July 2009

Objectives: To explore social inequalities in grip strength, SF-36 physical functioning (PF), and falls among older people. Methods: We analyzed data from 3,225 men and women (age 59-73 years) who participated in the Hertfordshire Cohort Study, United Kingdom. Car availability and home ownership were used as markers of material deprivation. Results: A total of 6.4% of men (17.7% women) had no car and 19.3% of men (23.1% women) did not own their home. Having fewer cars was associated with lower grip and poorer PF among men and women ( p < .001), and increased falls among men ( p < .001). Not owning one’s home was associated with lower grip in men and women ( p < .001) and poorer PF in men ( p < .001). Lower social class was associated with falls among women only ( p = .01). Discussion: There are social inequalities in grip strength, PF, and falls among older people. Interventions should consider the contribution of social inequalities to the problem.
Social Gastronomy
Authors: Sipe Daniel
Published: July 2009

This article examines the imbricating discourses of modernity in the works of Jean Anthelme Brillat-Savarin and Charles Fourier. In signalling significant intertextual relationships between Fourier's utopian writings and Brillat-Savarin's iconic gastronomic treatise, Physiologie du goût (first published 1825), the author proposes to elucidate the role that food writing played in fantasising about new forms of sociability in the post-Revolutionary period. Both Brillat-Savarin and Fourier propose a rational and pleasurable ordering of the objects and spaces of consumption, through which individual appetites and social function are harmonised. This pleasurable ordering is, it will be argued, the central operational imperative of an emerging class of gastronomic administrators. It is here, however, in the failed management of appetite, that the gastronomic systems of our like-minded authors can be seen to diverge, exposing the deeply political nature of the alimentary knowledge they propose.
Proceeding carefully: Assisted human reproduction policy in Canada
Authors: Jones Mavis , Salter Brian
Published: July 2009

The Canadian Act Respecting Assisted Human Reproduction and Related Research (AHR Act), which came into effect in 2004, was the culmination of fifteen years of policy development in this often controversial field. Drawing from a series of semi-structured elite interviews and extensive documentary research, we examine the path to policy for the AHR Act. We identified several influences on the Act’s development, including: 1) feminist-informed activism which found a balance between rejecting the medical model of reproduction and instituting protections against the commodifying potential of reproductive technologies; 2) Canada’s proximity to the United States (and its contrasting structures and stances); 3) the role of professional elites in supporting or resisting the proposed regulations; and 4) the tensions between federal and provincial jurisdiction in the Canadian federalist state. The path to this outcome provides an illuminating study of the tensions between internal and external pressures in the policy process.
Elite Women Wrestlers' Muscles
Authors: Sisjord Mari Kristin , Kristiansen Elsa
Published: July 2009

Wrestling is a male-dominated sport in terms of participation, commonly perceived as a masculine sport due to the requirement of muscular strength, courage, fighting spirit, as well as and the element of combat. Integral to achieving wrestling skills and physical capability is muscularity, something which may contradict common perceptions of feminine body appearance. The objective of this study is to examine female elite wrestlers' enactment of the wrestler's role and how they experienced enhancement of skills and bodily structure. This was done by means of a qualitative interview of eight Norwegian elite wrestlers comprising four females and four males in the age group 17 to 32 years. Since the wrestlers practice in a mixed gender setting the males were included as being part of the interaction. The study revealed different ways in which the female wrestlers were doing femininity which also seemed to be contextually bound. This was particularly related to strength training and overall performance as wrestlers. The seniors had apparently accepted strenuous strength training and big muscles, whereas the juniors were `holding back' giving priority to the `private body'. The seniors had accepted the `athletic body' and muscularity with its social costs.
Sport as a Vehicle for Social Mobility and Regulation of Disadvantaged Urban Youth
Authors: Spaaij Ramón
Published: July 2009

This article addresses sport's contribution to social mobility of disadvantaged urban youth through an analysis of the Sport Steward Program in Rotterdam, the Netherlands. Sport-based social intervention programs are conceptualized as potential vehicles for the creation of different forms of capital from which certain benefits can be derived that enable social agents to improve their social position. While the Sport Steward Program has contributed to objective and subjective social mobility of some participants, in most cases it is more suitable to highlight the relatively modest increases in participants' cultural, social and/or economic capital. However, rather than simply enhancing individual freedom and opportunity, sport-based intervention programs also serve as a form of social control and regulation. Sport is increasingly becoming a substantial aspect of the neoliberal policy repertoire of cities like Rotterdam aimed at generating social order in disadvantaged inner-city neighbourhoods.