bluuebunny/crossref_metadata_2025 huggingface dataset:
Low Diastolic Pressure and Risk of Dementia in Very Old People: A Longitudinal Study
Authors: Qiu Chengxuan , Winblad Bengt , Fratiglioni Laura
Published: September 2009

Background/Aim: Midlife high blood pressure is linked to late-life dementia. We sought to investigate the temporal relation of blood pressure to the risk of dementia and Alzhei-mer’s disease (AD) among older adults. Methods: A dementia-free cohort (n = 422) aged ≥81 years was followed for 3 years to detect dementia and AD cases (Diagnostic and Statistical Manual of Mental Disorders, Third Edition, Revised criteria). The blood pressure was measured 4 times over a 9-year period starting from ≥75 years of age. The data were analyzed with Cox models controlling for potential confounders. Results: During the 954 person-years of follow- up, 89 subjects developed dementia (72 AD cases). Low diastolic pressure (<70 vs. 70–89 mm Hg) was associated with a multiadjusted hazard ratio of 2.13 [95% confidence interval (CI) = 1.05–4.32] for dementia and 2.16 (95% CI = 0.98–4.73) for AD occurring over a 6-to 9-year period, whereas high diastolic pressure (≥90 mm Hg) was marginally related to a decreased hazard ratio of 0.58 (95% CI = 0.33–1.02) for dementia and 0.57 (95% CI = 0.30–1.09) for AD. Systolic pressure was not significantly related to dementia risk. Subjects who developed dementia had a greater decline in blood pressure than persons who did not, mainly during the 3-year period before dementia diagnosis. Conclusion: Low diastolic pressure predicts the risk of dementia among very old people, and the blood pressure exhibits a substantial decline over around 3 years before the dementia syndrome becomes clinically evident.
Effect of the Thromboxane Prostaglandin Receptor Antagonist Terutroban on Arterial Thrombogenesis after Repeated Administration in Patients Treated for the Prevention of Ischemic Stroke
Authors: Bal dit Sollier C. , Crassard I. , Simoneau G. , Bergmann J.-F. , Bousser M.G. , Drouet L.
Published: September 2009

Background: The antithrombotic, antiplatelet and endothelial activity of terutroban, a specific thromboxane prostaglandin receptor antagonist, was assessed in patients previously treated with aspirin for the prevention of ischemic stroke. Methods: This double-blind, parallel-group, 10-day study included 48 patients (age = 70.5 ± 9.5 years) with cerebral ischemic event and/or carotid stenosis in 4 groups: terutroban 10 mg/day (n = 13), aspirin 300 mg/day (n = 12), terutroban 10 mg/day + aspirin 300 mg/day (n = 11) or clopidogrel 75 mg/day + aspirin 300 mg/day (n = 12). The measurements included parameters from an ex vivo model of thrombosis, platelet aggregation in platelet-rich plasma and plasma biomarkers of endothelial/platelet activation. Results: Between days 0 and 10, the mean cross-sectional surface of dense thrombus significantly decreased with terutroban (58%, p = 0.001), terutroban + aspirin (63%, p = 0.005) and clopidogrel + aspirin (61%, p < 0.05). On day 10, the value for terutroban was significantly lower than that for aspirin (p < 0.01) and was comparable to the dual therapy terutroban + aspirin or clopidogrel + aspirin. Similar results were found for total thrombus surface and platelet adhesion. Platelet aggregation induced by the specific thromboxane prostaglandin receptor agonist U46619 was almost completely inhibited on day 10 in both terutroban groups but not in the others. As regards markers of endothelial/platelet activation or lesions, thrombomodulin significantly increased and plasma soluble P selectin significantly decreased by day 10 in both terutroban groups, whereas the von Willebrand factor did not change significantly. Terutroban was found to be safe and well tolerated. Conclusions: Terutroban has demonstrated an antithrombotic activity that is superior to aspirin and similar to clopidogrel + aspirin; it induces a significant in vivo reduction in endothelial/platelet activation.
A Case of Pulmonary Lymphomatoid Granulomatosis Successfully Treated by Combination Chemotherapy with Rituximab
Authors: Jung Ki Hwan , Sung Hwa Jung , Lee Ju-Han , Lee Ki Yeol , Shin Jae Seung , Kim Kyung Min , Kim Young-Sik , Shin Chol , Kim Je Hyeong
Published: September 2009

Lymphomatoid granulomatosis (LYG) is a rare angiocentric and angiodestructive lymphoproliferative disease characterized by Epstein-Barr virus-positive B cells admixed with reactive T cells. LYG most commonly affects the lung but can also involve other extrapulmonary sites. Pulmonary LYG usually presents as multiple pulmonary nodules with rapid progression and excavation. It can mimic various infectious diseases, vasculitis or metastatic malignancy and is difficult to be diagnosed clinically. Standard treatment for LYG has not yet been established. Despite combination chemotherapy, the overall prognosis is poor. Recently, anti-CD20 monoclonal antibody, rituximab, has been used to treat LYG. We report the case of a 70-year-old male patient with pulmonary LYG, who showed rapid remission of the disease after combination chemotherapy with rituximab.
Once-Weekly Administration of Etanercept 50 mg Improves Patient-Reported Outcomes in Patients with Moderate-to-Severe Plaque Psoriasis
Authors: Reich Kristian , Segaert Siegfried , Van de Kerkhof Peter , Durian Cis , Boussuge Marie Pierre , Paolozzi Laurence , Wajdula Joseph , Boggs Robert
Published: September 2009

Objective: To assess baseline patient-reported outcomes (PROs) and PRO improvement in patients with psoriasis administered etanercept 50 mg once weekly (QW). Methods: Adult patients with moderate-to-severe plaque psoriasis participated in a 12-week, double-blind, controlled trial in which they received etanercept 50 mg QW (n = 96) or placebo QW (n = 46), followed by a 12-week, open-label extension in which they received etanercept 50 mg QW (etanercept-etanercept, n = 90; placebo-etanercept, n = 36). Patients completed the Dermatology Life Quality Index (DLQI), EuroQoL-5D (EQ-5D) and Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) at baseline and subsequent study visits. Results: At baseline, DLQI and EQ-5D scores indicated significant quality of life (QoL) impairment, and FACIT-F scores suggested more fatigue than in the general population. At week 12, etanercept 50 mg QW provided statistically significantly (p < 0.05) and clinically meaningfully greater improvement in DLQI and EQ-5D utility scores than placebo, but not in FACIT-F scores. After 24 weeks of etanercept, the mean DLQI suggested psoriasis had a small effect on QoL, while EQ-5D and FACIT-F scores were comparable to population norms. Conclusions: Patients with moderate-to-severe psoriasis entered this trial with serious PRO impairment. At week 12, etanercept 50 mg QW provided significant QoL improvements compared with placebo. After 24 weeks of etanercept, the patients’ serious PRO impairment had largely abated.
Inflammation and Anti-Inflammatory Strategies for Alzheimer’s Disease – A Mini-Review
Authors: McNaull Benjamin Brian Alexander , Todd Stephen , McGuinness Bernadette , Passmore Anthony Peter
Published: September 2009

Until recently, the central nervous system (CNS) has been thought to be an immune privileged organ. However, it is now understood that neuroinflammation is linked with the development of several CNS diseases including late-onset Alzheimer’s disease (LOAD). The development of inflammation is a complex process involving a wide array of molecular interactions which in the CNS remains to be further characterized. The development of neuroinflammation may represent an important link between the early stages of LOAD and its pathological outcome. It is proposed that risks for LOAD, which include genetic, biological and environmental factors can each contribute to impairment of normal CNS regulation and function. The links between risk factors and the development of neuroinflammation are numerous and involve many complex interactions which contribute to vascular compromise, oxidative stress and ultimately neuroinflammation. Once this cascade of events is initiated, the process of neuroinflammation can become overactivated resulting in further cellular damage and loss of neuronal function. Additionally, neuroinflammation has been associated with the formation of amyloid plaques and neurofibrillary tangles, the pathological hallmarks of LOAD. Increased levels of inflammatory markers have been correlated with an advanced cognitive impairment. Based on this knowledge, new therapies aimed at limiting onset of neuroinflammation could arrest or even reverse the development of the disease.
Noninvasive Home Mechanical Ventilation in Elderly Patients
Authors: Crespo Astrid , Muñoz Xavier , Torres Ferran , Martí Sergi , Ferrer Jaume , Morell Ferran
Published: September 2009

Study Objective: To determine the short- and long-term benefits of noninvasive home mechanical ventilation (NIHMV) in patients aged 65 and older who were eligible for this treatment. Design and Setting: This retrospective, comparative, longitudinal study was carried out in a tertiary care hospital in Barcelona (Spain). Patients and Methods: The study included all patients in whom NIHMV with a nasal mask was established in the period from 1998 to 2001. Patients were divided into 3 groups according to age: group 1 (n = 10) ≧75; group 2 (n = 40) 65–74, and group 3 (n = 41) <65 years old. Clinical characteristics, pulmonary function results, and arterial blood gas findings were assessed in all patients before starting ventilation and after 6 months. Measurements and Results: Statistically significant improvements in PaO2 (13.4, 10, and 15.3 mm Hg for groups 1–3) and PaCO2 (–17.6, –9.6 and –12.8 mm Hg for groups 1–3) were found at 6 months (p < 0.001 in all cases). There were no significant differences between the groups in blood gas parameters and treatment compliance. The incidence of related adverse events was not statistically different between the study groups (40%, 35% and 32% for groups 1–3; p = 0.859). Conclusions: NIHMV is effective in all patients for whom it is indicated, regardless of their age.
Proactive and Coactive Interference in Age-Related Performance in a Recognition-Based Operation Span Task
Authors: Zeintl Melanie , Kliegel Matthias
Published: September 2009

Background: Generally, older adults perform worse than younger adults in complex working memory span tasks. So far, it is unclear which processes mainly contribute to age-related differences in working memory span. Objective: The aim of the present study was to investigate age effects and the roles of proactive and coactive interference in a recognition-based version of the operation span task. Methods: Younger and older adults performed standard versions and distracter versions of the operation span task. At retrieval, participants had to recognize target words in word lists containing targets as well as proactive and/or coactive interference-related lures. Results: Results show that, overall, younger adults outperformed older adults in the recognition of target words. Furthermore, analyses of error types indicate that, while younger adults were only affected by simultaneously presented distracter words, older adults had difficulties with both proactive and coactive interference. Conclusion: Results suggest that age effects in complex span tasks may not be mainly due to retrieval deficits in old age.
Age-Related Changes of Anti-Elastin Antibodies in Senescence-Accelerated Mice
Authors: Atanasova Milena , Konova Emiliana , Georgieva Miglena , Dimitrova Anelja , Coquand-Gandit Marion , Faury Gilles , Baydanoff Stephan
Published: September 2009

Background: Antibodies recognizing the elastin precursor tropoelastin (ATEAb) or degradation products α-elastin (AEAb) are found in the serum of healthy human subjects, as a part of a homeostatic mechanism which assembles new or clears altered elastin structures. Serum ATEAb (reflecting elastin synthesis) and AEAb (reflecting elastin destruction) appear to correlate with the production and breakdown of the elastic tissue, respectively. Objective: The aim of this study was to investigate plasma levels of AEAb and ATEAb in senescence-accelerated prone (SAMP8) and senescence-accelerated resistant (SAMR1) mice, compared with imprinting control region (ICR) mice in order to evaluate their age-related changes. Methods: The levels of AEAb and ATEAb were measured by home-made ELISA in plasma of SAMP8, SAMR1, and ICR mice, grouped according to their age (3 and 9 months) and sex. The specificity of AEAb and ATEAb activity in mouse plasma, and elastin-derived peptides (EDP) in sera of ICR mice at 3 and 9 months of age were tested by competitive ELISA. Results: The specificity of AEAb and ATEAb in mouse plasma was confirmed by the competitive investigations. The levels of AEAb in the plasma of SAMR1 and SAMP8 were increased compared to the levels measured in ICR on the matched ages (p < 0.001). Age-related increase of the levels of AEAb and ATEAb was established in the 3 strains (p < 0.001). Significantly higher levels of AEAb were established in female 9-month-old mice compared to males in all strains. The ATEAb:AEAb ratio was significantly lower in the SAM compared to the ICR strain. Positive correlation was established between the levels of serum AEAb and EDP in mouse sera of ICR mice. Conclusion: Variations with age in the plasma levels of AEAb and ATEAb were established in SAM compared with ICR, and in SAMP8 compared with SAMR1. Our findings suggest that increased anti-elastin IgG autoantibodies could be used as a marker of aging in SAM and possibly contribute to the processes of aging. The absence of a difference between SAMP8 and SAMR1 regarding the ATEAb:AEAb ratio raises the question if SAMR1 are an appropriate control of SAMP8 in terms of the senescence of the elastic tissues.
Beneficial Effects of Combination Therapy with Olmesartan and Azelnidipine in Murine Polycystic Kidneys
Authors: Tanifuji Chiaki , Suzuki Yusuke , Geot Wong Mu , Horikoshi Satoshi , Takahashi Hisahide , Tomino Yasuhiko
Published: September 2009

Background: Some reports have discussed the synergic effects of angiotensin II receptor blockers and calcium channel blockers on vascular injury or microalbuminuria. The present study examined the effects of combination treatment with olmesartan and azelnidipine on polycystic kidney disease in a mouse model (DBA/2-FG pcy mouse) and its mechanisms. Methods: The mice were divided into the following groups: combination treatment (n = 21), olmesartan treatment alone (n = 23), azelnidipine treatment alone (n = 29) or untreated (n = 26). Mean blood pressure and kidney weight were measured at 4 and 8 weeks after the treatment. Renal expression of angiotensin II, gp91, nitrotyrosine and endothelial NO synthase (eNOS) were examined by immunostaining. In addition, extracellular signal-regulated kinase activation was evaluated by Western blotting. Results: Olmesartan decreased the numbers of angiotensin II and gp91-positive cells, mainly macrophages, and cyst size at 4 weeks. However, only combination treatment suppressed cell infiltration, extracellular signal-regulated kinase activation and interstitial fibrosis with a significant change in the kidney weight/body weight ratio. The azelnidipine and combination treatment increased the numbers of interstitial eNOS-positive cells. Conclusion: The combination treatment protects against cyst enlargement in polycystic kidney disease by suppressing interstitial inflammation, fibrosis and oxidative stress by upregulating eNOS expression during disease course.
Tumor Necrosis Factor-α Potentiates RhoA-Mediated Monocyte Transmigratory Activity In Vivo at a Picomolar Level
Authors: Lim Sunny , Ryu Jewon , Shin Jin-Ae , Shin Min-Jung , Ahn Yeong Ki , Kim Jae Joong , Han Ki Hoon
Published: September 2009

Objective—

The serum level of tumor necrosis factor-α (TNF-α) is in the picomolar range under inflammatory conditions. We investigated whether these picomolar levels of TNF-α directly modulate the functional activities of circulating monocytes.

Methods and Results—

In THP-1 monocytes treated with TNF-α (1 to 100 pmol/L/30 minutes), cytosolic RhoA small GTPase rapidly translocated to the plasma membrane via functionally active ezrin/radixin/moesin (ERM) complex, a cytoskeletal linker, and subsequent actin polymerization through NF-κB activation. The threonine phosphorylation of ERM was accomplished by the activation of TNF receptor type I (TNFRI) and signaling pathways involving PI3K and an atypical PKC; ie, PKCζ. The TNF-α-treated monocytes (10 pmol/L) displayed more potent and prolonged generation of GTP-bound RhoA in response to secondary stimulation with RhoA-activating monocyte chemoattractant protein-1 (MCP-1). Clearly, human circulating monocytes preconditioned by 10 pmol/L TNF-α augmented MCP-1–mediated chemotaxis and firm adhesion on VCAM-1 and ICAM-1 in vitro and ex vivo. The elevation of serum TNF-α (>5 pmol/L within 16 hours), which was introduced by intraperitoneal injection of mouse-specific TNF-α to C57/BL6 mice, enhanced the number of CD80+ monocytes transmigrating to the JE/MCP-1–injected intraperitoneal space.

Conclusions—

Picomolar concentrations of TNF-α in the bloodstream may prime the RhoA-dependent activities of circulating monocytes to enhance recruitment to active inflammatory foci.
Dual Pathways of Carbon Monoxide–Mediated Vasoregulation
Authors: Lamon Brian D. , Zhang Frank F. , Puri Nitin , Brodsky Sergey V. , Goligorsky Michael S. , Nasjletti Alberto
Published: September 2009

Rationale
:

Vascular tissues produce carbon monoxide (CO) via HO-dependent and HO-independent mechanisms; the former in tandem with biliverdin and iron and the latter as a lone product. CO has been shown to function as both a vasoconstrictor and vasodilator; however, factors that dictate the vasoregulatory phenotype of this gas are unknown.

Objective
:

We investigated whether CO-mediated vasoconstriction is mechanistically linked to enhanced reactive oxygen species production that masks vasodilatory pathways.

Methods and Results
:

Sprague–Dawley rat interlobar and interlobular arteries were examined in terms of superoxide (O
2
·−
) generation and vascular reactivity in the absence and presence of antioxidants. Both authentic CO and the CO-releasing molecule (CORM)-3 constricted renal arteries and increased O
2
·−
production in a dose-dependent manner. The antioxidants tempol, ebselen, and deferoxamine inhibited CO-induced O
2
·−
production and converted CO from constrictor to dilator. CO-induced O
2
·−
generation was found to involve the activity of multiple oxidases including nitric oxide synthase, NADPH oxidase, xanthine oxidase, and complex IV of the mitochondrial electron chain. Furthermore, inhibition of these enzymes converted CO from constrictor to dilator. Similarly, biliverdin and bilirubin inhibited CO-induced O
2
·−
production and vasoconstriction, allowing for a vasodilatory response to CO to be expressed. CO-induced vasoconstriction was dependent on a non-thromboxane agonist of the thromboxane receptor, whereas vasodilatory mechanisms of CO relied on the activation of soluble guanylate cyclase and calcium-gated potassium channels.

Conclusions
:

CO-induced vasoconstriction involves the generation of reactive oxygen species, which, when negated, allows for the expression of vasodilatory pathways which are masked by the primary oxidative stress response to this gas.
Effects of Moderate-Dose Omega-3 Fish Oil on Cardiovascular Risk Factors and Mood After Ischemic Stroke
Authors: Poppitt Sally D. , Howe Colin A. , Lithander Fiona E. , Silvers Karen M. , Lin Ruey-Bin , Croft John , Ratnasabapathy Yogini , Gibson Robert A. , Anderson Craig S.
Published: September 2009

Background and Purpose—

Fish-derived omega-3 fatty acids have long been associated with cardiovascular protection. In this trial, we assessed whether treatment with a guideline-recommended moderate-dose fish oil supplement could improve cardiovascular biomarkers, mood- and health-related quality of life in patients with ischemic stroke.

Methods—

Patients with CT-confirmed stroke were randomized to 3 g/day encapsulated fish oil containing approximately 1.2 g total omega-3 (0.7 g docosahexaenoic acid; 0.3 g eicosapentaenoic acid) or placebo oil (combination palm and soy) taken daily over 12 weeks. Serum triglycerides, total cholesterol and associated lipoproteins, selected inflammatory and hemostatic markers, mood, and health-related quality of life were assessed at baseline and follow-up. The primary outcome was change in triglycerides. Compliance was assessed by capsule count and serum phospholipid omega-3 levels (Australian Clinical Trials Registration: ACTRN12605000207617).

Results—

One hundred two patients were randomized to fish oil or placebo. Intention-to-treat and per-protocol (>85% compliance) analyses showed no significant effect of fish oil treatment on any lipid, inflammatory, hemostatic, or composite mood parameters measured. Adherence to treatment based on pill count was good (89%) reflected by increased serum docosahexanoic acid (
P
<0.001) and eicosapentaenoic acid (
P
=0.0006) in the fish oil group. Analysis of oil composition, however, showed some degradation and potentially adverse oxidation products at the end of the study.

Conclusions—

There was no effect of 12 weeks of treatment with moderate-dose fish oil supplements on cardiovascular biomarkers or mood in patients with ischemic stroke. It is possible that insufficient dose, short duration of treatment, and/or oxidation of the fish oils may have influenced these outcomes.
Diagnostic Usefulness of the ABCD
2
Score to Distinguish Transient Ischemic Attack and Minor Ischemic Stroke From Noncerebrovascular Events
Authors: Sheehan Orla C. , Merwick Aine , Kelly Lisa A. , Hannon Niamh , Marnane Michael , Kyne Lorraine , McCormack Patricia M.E. , Duggan Joseph , Moore Alan , Moroney Joan , Daly Leslie , Harris Dawn , Horgan Gillian , Kelly Peter J.
Published: September 2009

Background and Purpose—

Transient ischemic attack (TIA) diagnosis is frequently difficult in clinical practice. Noncerebrovascular symptoms are often misclassified as TIA by nonspecialist physicians. Clinical prediction rules such as ABCD
2
improve the identification of patients with TIA at high risk of early stroke. We hypothesized that the ABCD
2
score may partly improve risk stratification due to improved discrimination of true TIA and minor ischemic stroke (MIS) from noncerebrovascular events.

Methods—

Consecutive patients with TIA were identified within a prospective population-based cohort study of stroke and TIA. The cohort was expanded by inclusion of patients with MIS and noncerebrovascular events referred to a daily TIA clinic serving the population. Diagnosis was assigned by a trained stroke physician independent of ABCD
2
score.

Results—

Five hundred ninety-four patients were included (292 [49.2%] TIA, 45 [7.6%] MIS, and 257 [43.3%] noncerebrovascular). The mean ABCD
2
score showed a graded increase across diagnostic groups (MIS mean 4.8 [SD 1.4] versus TIA mean 3.9 [SD 1.5] versus noncerebrovascular mean 2.9 [SD 1.5];
P
<0.00001). The ABCD
2
score discriminated well between noncerebrovascular and cerebrovascular events—TIA (c-statistic 0.68; 95% CI, 0.64 to 0.72), any vascular event (TIA+MIS; c-statistic 0.7; 95% CI, 0.66 to 0.74), and MIS (c-statistic 0.81; 95% CI, 0.75 to 0.87)—from noncerebrovascular events. Of ABCD
2
items, unilateral weakness (OR, 4.5; 95% CI, 3.1 to 6.6) and speech disturbance (OR, 2.5; 95% CI, 1.6, 4.1) were most likely overrepresented in TIA compared with noncerebrovascular groups.

Conclusion—

The ABCD
2
score had significant diagnostic usefulness for discrimination of true TIA and MIS from noncerebrovascular events, which may contribute to its predictive usefulness.
Intravenous Tissue Plasminogen Activator in Patients With Cocaine-Associated Acute Ischemic Stroke
Authors: Martin-Schild Sheryl , Albright Karen C. , Misra Vivek , Philip Maria , Barreto Andrew D. , Hallevi Hen , Grotta James C. , Savitz Sean I.
Published: September 2009

Background and Purpose—

The safety of thrombolytic therapy in patients with cocaine-associated acute ischemic stroke (CIS) is unknown.

Methods—

We conducted a retrospective review of patients with CIS who presented to our stroke center. Thrombolytic treatment was compared between cocaine-positive (n=29) and cocaine-negative (n=75) patients. We also compared patients with CIS treated with tissue plasminogen activator versus those who did not receive tissue plasminogen activator (n=58). Safety outcomes were determined by the incidence of symptomatic intracerebral hemorrhage, in-hospital mortality, and modified Rankin Scale at hospital discharge.

Results—

There were no complications in tissue plasminogen activator-treated patients with CIS. Cocaine-positive and cocaine-negative treated patients had similar stroke severity and safety outcomes. Patients with CIS treated with tissue plasminogen activator had more severe strokes on baseline National Institutes of Health Stroke Scale but similar safety outcomes compared with nontreated patients with CIS.

Conclusion—

Thrombolytic therapy for CIS appears to be safe in this small study. Further research is needed to more definitively assess safety and efficacy of tissue plasminogen activator for CIS.
Pharmacologic Interventions for Stroke
Authors: Chavez Juan C. , Hurko Orest , Barone Frank C. , Feuerstein Giora Z.
Published: September 2009

Background and Purpose—

The majority of pharmacological agents for stroke were developed based on the assumption that neurological deficits will be reduced upon the successful interruption of biochemical mechanisms leading to neuronal death. Despite significant evidence of preclinical efficacy, none of these agents succeeded. They either failed to demonstrate efficacy in the clinic or their development was halted for safety, strategic, or commercial reasons.

Summary of Review—

This “neuroprotection strategy” has focused primarily on targets in the neurotoxic environment that occurs under ischemic conditions. In many cases, these agents were designed to tackle events that are known to start almost immediately after onset of ischemia, which is far before a realistic therapeutic time window opens for most, if not all, patients with stroke. In other instances, they were evaluated beyond a realistic timeframe in which one could expect significant salvageable tissue or penumbra to exist. Surprisingly, most of these agents were not evaluated in conjunction with strategies for improving perfusion to the affected tissue, indicating an overoptimistic assumption that neuroprotection alone could be sufficient to halt injury caused by an abrupt interruption of brain blood flow.

Conclusions—

We provide a constructive translational medicine perspective about how one could improve the drug development process with the hope that the probability for success can increase in our quest to establish a novel therapy for stroke.
Attenuation of Brain Response to Vascular Endothelial Growth Factor-Mediated Angiogenesis and Neurogenesis in Aged Mice
Authors: Gao Peng , Shen Fanxia , Gabriel Rodney Allanigue , Law David , Yang Ethan Yibo , Yang Guo-Yuan , Young William L. , Su Hua
Published: September 2009

Background and Purpose—

Alterations of neuroangiogenic response play important roles in the development of aging-related neurodisorders and affect gene-based therapies. We tested brain response to vascular endothelial growth factor (VEGF) in aged mice.

Methods—

Adeno-associated viral vector (AAV)-VEGF, an adeno-associated viral vector expressing VEGF, was injected into the brain of 3-, 12-, and 24-month-old mice. AAV-LacZ-injected mice were used as controls (n=6). Before euthanasia at 6 weeks after vector injection, the mice were intraperitoneally injected with 5-bromodeoxyuridine for 3 consecutive days. The vascular density and the number of neuroprogenitors were analyzed.

Results—

Injection of AAV-VEGF increased the vascular density in the brain of 3-, 12-, and 24-month-old mice by 22%±7% (AAV-VEGF: 320±15 per 10× field versus AAV-LacZ: 263±8,
P
<0.05), 20%±8 (AAV-VEGF: 300±9 versus AAV-LacZ: 250±11,
P
<0.05), and 7%±16% (AAV-VEGF: 257±27 versus AAV-LacZ: 236±13,
P
=0.283), respectively. There were more VEGF receptor-positive neuroprogenitors in the subventricular zone of AAV-VEGF-injected 3- (22±2) and 12-month-old mice (21±5) than that of 24-month-old mice (7±1). More 5-bromodeoxyuridine-positive endothelial cells and neuroprogenitors were detected around the injection site and subventricular zone of 3- (13±4) and 12-month-old mice (14±5) than that of 24-month-old mice (1±1). VEGF receptor 2 was upregulated in AAV-VEGF-injected brains of 3- and 12-month-old mice, but not in 24-month-old mice.

Conclusion—

The angiogenic and neurogenic response to VEGF stimulation is attenuated in the aged mouse brain, which may be due to reduced VEGF receptor activity.
Pediatrician’s Role in Children’s Oral Health: An Indiana Survey
Authors: Ditto Marcus R. , Jones James E. , Sanders Brian , Weddell James A. , Jackson Richard , Tomlin Angela
Published: September 2009

Objectives. To evaluate Indiana pediatricians’ current practices related to oral health, knowledge of oral health prevention, and opinions on anticipatory guidance integration into their practices. Background. The American Academy of Pediatrics (AAP) May 2003 policy statement on oral health risk assessment timing and establishment of a dental home has provided pediatricians with guidelines to assess patients’ oral health and caries risk status. Methods. A survey of 31 questions was distributed via mail to all active Indiana pediatricians (300) registered in the Indiana State Medical Association to evaluate current practices relating to oral health prevention and guidance. Results. Of the 300 distributed surveys, 138 were returned (46%). The authors found that 15% of pediatricians recognize the AAP-recommended age for a dental home as 12 months and practice this recommendation. Among the respondents, 7% believe application of fluoride should be part of a well-child visit. The majority (89%) of respondents reported interest in obtaining further knowledge on oral health.
Self-Cultivation
Authors: Hwang Kwang-Kuo , Chang Jeffrey
Published: September 2009

This article describes self-cultivation practices originating from the cultural traditions of Confucianism, Taoism, and Buddhism. It delineates the therapeutic implications of the three states of self pursued by these three traditions: namely, the relational self , the authentic self, and the nonself. Several psychotherapy techniques derived from each of these traditions are discussed in the context of contemporary Confucian societies in East Asia and North America. The indigenous approach to understanding psychotherapies within a cultural context may contribute to the training program of multicultural counseling psychology.
Partisan Divide on War and the Economy
Authors: Fox Gerald T.
Published: September 2009

This study examines the influence of 9/11, the Iraq War, the economy, and the coalition-of-minorities on presidential approval of G. W. Bush across partisan subgroups and aggregate popularity. The analysis considers the effect of underlying partisan preferences on overall approval. A partisan divide occurs for war and the economy on Bush popularity. The events of 9/11 and the Iraq War affect Democratic opinions of Bush more than Republican opinions, whereas the economy impacts Republicans more than Democrats. An in-party/out-party rally effect occurs. Democrats show stronger rallies than Republicans for 9/11 and the Iraq War, but also faster and deeper popularity decay of the rallies. All economic and war-related effects significantly influence Independents and aggregate Bush popularity. The coalition-of-minorities pattern of declining presidential approval is caused by the 9/11 rally decay effect, the war casualties effect, and the slowing economy during Bush’s second term in office.
The Role of Working Memory and Fluency Practice on the Reading Comprehension of Students Who Are Dysfluent Readers
Authors: Swanson H. Lee , O'Connor Rollanda
Published: September 2009

The authors investigated whether practice in reading fluency had a causal influence on the relationship between working memory (WM) and text comprehension for 155 students in Grades 2 and 4 who were poor or average readers. Dysfluent readers were randomly assigned to repeated reading or continuous reading practice conditions and compared with untreated dysfluent and fluent readers on posttest measures of fluency, word identification, vocabulary, and reading comprehension. Three main findings emerged: (a) The influence of WM on text comprehension was not related to fluency training, (b) dysfluent readers in the continuous-reading condition had higher posttest scores than dysfluent readers in the other conditions on measures of text comprehension but not on vocabulary, and (c) individual differences in WM better predicted posttest comprehension performance than word-attack skills. In general, the results suggested that although continuous reading increased comprehension, fluency practice did not compensate for WM demands. The results were interpreted within a model that viewed reading comprehension processes as competing for a limited supply of WM resources that operate independent of fluency.
The Assault upon Kings and Tyrants in the Moses Tradition
Authors: Gnuse Robert K.
Published: September 2009

The biblical traditions concerning Moses in the book of Exodus and Numbers contain an obvious critique of tyrannical kings and their oppressive deeds, as dramatically metaphored by pharaoh and his actions. Movies and cartoons over the years have captured the power of this dramatic symbolism. A close reading of the text unveils how even more deeply penetrating this critique of power and the wielders of power is within our biblical narratives. At times with deadly seriousness and at times with humor our biblical author assaults the prerogatives of kings and their advisers. This essay is not so much a scholarly exposition as a theological reflection upon the powerful political imagery of our sacred text. Too often in our biblical theology we fail to appreciate the depth of the biblical assault upon tyranny and the corresponding affirmation of human freedom and equality.
Environmental risk factors and children’s literacy skills during the transition to elementary school
Authors: Cadima Joana , McWilliam R.A. , Leal Teresa
Published: September 2009

This study examined the effects of the accumulation of family risk factors on children’s literacy skills, both in preschool and in first grade. Children’s ( N = 106) vocabulary, conventions of print, phonological awareness, knowledge of letters, reading decoding, and reading comprehension were assessed. Family risk factors, consisting of household composition, years of maternal education, job situation of the mother, and income level of the family, were combined to create a cumulative risk index. Canonical correlation and multiple regression analyses were performed. Results revealed the negative impact of cumulative risk index on both the preschool and first-grade literacy skills. In addition, the number of risk factors present in the family context negatively predicted the majority of the firstgrade literacy skills, after taking preschool skills into account. The results provide further evidence of the negative impact of the accumulation of family risks on child literacy development and call attention to the importance of early experiences for later academic achievement.
Palestinian Politics after Arafat
Authors: Ghanem As'ad
Published: September 2009

This article attempts to understand the internal situation of the Palestinians and their national movement at the start of the twenty-first century. I hereby attempt to trace and analyze concrete aspects of the state of the Palestinian national movement in the post-Oslo era. What happened during the past decade to the Palestinians in general, and to their national movement in particular, led to the internal and external failure. Externally, this failure was manifested in the disintegration of the regional and international status of the Palestinian national movement. Concomitantly, the efforts to establish a Palestinian state and resolve the conflict reached a dead end because of the deep internal schism which had developed, and which is incompatible with national unity.
Why Select New Music Teachers Chose to, or Chose Not to, Apply to Teach in an Urban School District
Authors: Bruenger Susan Dill
Published: September 2009

The purpose of this investigation is to describe the criteria that highly qualified music-education students with cultural diversity training from a Hispanic-serving institution used in their decision to apply or not apply to teach in an urban district on graduation. Eleven participants were selected. Three of them applied to an urban district and one accepted an urban job. Findings from employment inducement studies formed the theoretical basis to analyze the criteria the participants used to make their employment decisions. Content analysis of open-ended interviews reveals the importance of the following criteria in making the decision to apply to teach in an urban school district: the participants’ perceptions of the match of their own values to the organization’s values, specifically, whether they would be able to achieve what they wanted to and the proximity of the school district to where the participant grew up. These participants did not place great importance on salary. The finding of most interest is that the four participants who did not apply to teach in an urban district instead accepted jobs in midurban Title One schools, thereby teaching the same socioeconomic population they would have taught in an urban school. These particular participants were willing to teach students in lower socioeconomic circumstances, but they wanted to do so in a district where they believed that their ensembles would be competitive.
The Effective Number of Parties
Authors: Golosov Grigorii V.
Published: September 2009

The Laakso—Taagepera index of the effective number of parties, while satisfying most of the requirements of this aggregate quantity, tends to produce unrealistically high scores for party constellations in which the shares of the largest parties exceed 50 percent, and can produce misleading results in several other situations. After reviewing the structural properties of the Laakso—Taagepera index and supplements or alternatives to it proposed in the literature, this article proposes a new index that eliminates several problems inherent in the mathematical form of indices using the Herfindahl—Hirschman measure of concentration as computational core. The proposed index is tested on a set of party constellations from recent elections in new democracies and non-democratic electoral regimes. The results confirm that the new index works better than earlier proposed alternatives in measuring the effective number of components in highly fragmented and highly concentrated party systems.
Sonography in the Diagnosis of Renal Transplant Torsion
Authors: Gutknecht Mary
Published: September 2009

Torsion following kidney transplant is a complication occurring when the kidney rotates around the vascular pedicle. It is a relatively rare occurrence but one that the sonographer should be aware of when a patient presents with severe abdominal pain and decreased urine output. In the best of circumstances, renal torsion can be repaired; in the worst cases, the kidney is lost. Prompt diagnosis of renal vein thrombosis, renal artery stenosis, and occlusion resulting from torsion permits graft detorsion and possible salvage of the kidney.
Characterization of complement factor H–related (CFHR) proteins in plasma reveals novel genetic variations of CFHR1 associated with atypical hemolytic uremic syndrome
Authors: Abarrategui-Garrido Cynthia , Martínez-Barricarte Rubén , López-Trascasa Margarita , Rodríguez de Córdoba Santiago , Sánchez-Corral Pilar
Published: September 2009

The factor H–related protein family (CFHR) is a group of minor plasma proteins genetically and structurally related to complement factor H (fH). Notably, deficiency of CFHR1/CFHR3 associates with protection against age-related macular degeneration and with the presence of anti-fH autoantibodies in atypical hemolytic uremic syndrome (aHUS). We have developed a proteomics strategy to analyze the CFHR proteins in plasma samples from controls, patients with aHUS, and patients with type II membranoproliferative glomerulonephritis. Here, we report on the identification of persons carrying novel deficiencies of CFHR1, CFHR3, and CFHR1/CFHR4A, resulting from point mutations in CFHR1 and CFHR3 or from a rearrangement involving CFHR1 and CFHR4. Remarkably, patients with aHUS lacking CFHR1, but not those lacking CFHR3, present anti-fH autoantibodies, suggesting that generation of these antibodies is specifically related to CFHR1 deficiency. We also report the characterization of a novel CFHR1 polymorphism, resulting from a gene conversion event between CFH and CFHR1, which strongly associates with aHUS. The risk allotype CFHR1*B, with greater sequence similarity to fH, may compete with fH, decreasing protection of cellular surfaces against complement damage. In summary, our comprehensive analyses of the CFHR proteins have improved our understanding of these proteins and provided further insights into aHUS pathogenesis.
Evaluation of pentostatin in corticosteroid-refractory chronic graft-versus-host disease in children: a Pediatric Blood and Marrow Transplant Consortium study
Authors: Jacobsohn David A. , Gilman Andrew L. , Rademaker Alfred , Browning Brittan , Grimley Michael , Lehmann Leslie , Nemecek Eneida R. , Thormann Kimberly , Schultz Kirk R. , Vogelsang Georgia B.
Published: September 2009

There is no standard therapy for steroid-refractory chronic graft-versus-host disease (GVHD). This problem is particularly daunting in children with chronic GVHD, whereby the effects of the disease and its treatment may impair normal growth and development. Children are also particularly vulnerable to failure and/or toxicity of therapy; for example, joint contractures or joint damage may result in life-long disability. The Pediatric Blood and Marrow Transplant Consortium performed a phase 2 trial of pentostatin for steroid-refractory chronic GVHD in 51 children (median age, 9.8 years) from 24 institutions. Overall response was 53% (95% confidence interval, 40%-64%), with a response of 59% (95% confidence interval, 42%-75%) in sclerosis. Thirteen subjects (25%) had toxicity requiring them to stop pentostatin. The drug had a significant steroid-sparing effect in those that responded. A trend was also observed toward increased survival at 3 years in responders versus nonresponders (69% vs 50%; P = .06). The intravenous administration of the drug ensures compliance in a patient group in which oral therapy is difficult to monitor. Pentostatin has activity in refractory chronic GVHD in children, and future studies, including treatment of children newly diagnosed with high-risk chronic GVHD, are warranted. The trial was registered at www.Clinicaltrials.gov as #NCT00144430.
Identification of a region required for TSC1 stability by functional analysis of TSC1missense mutations found in individuals with tuberous sclerosis complex
Authors: Mozaffari Melika , Hoogeveen-Westerveld Marianne , Kwiatkowski David , Sampson Julian , Ekong Rosemary , Povey Sue , den Dunnen Johan T , van den Ouweland Ans , Halley Dicky , Nellist Mark
Published: September 2009

Background

Tuberous sclerosis complex (TSC) is an autosomal dominant disorder characterised by the development of hamartomas in a variety of organs and tissues. The disease is caused by mutations in either the TSC1 gene on chromosome 9q34, or the TSC2 gene on chromosome 16p13.3. The TSC1 and TSC2 gene products, TSC1 and TSC2, form a protein complex that inhibits signal transduction to the downstream effectors of the mammalian target of rapamycin (mTOR). Recently it has been shown that missense mutations to the TSC1 gene can cause TSC.

Methods

We have used in vitro biochemical assays to investigate the effects on TSC1 function of TSC1 missense variants submitted to the Leiden Open Variation Database.

Results

We identified specific substitutions between amino acids 50 and 190 in the N-terminal region of TSC1 that result in reduced steady state levels of the protein and lead to increased mTOR signalling.

Conclusion

Our results suggest that amino acid residues within the N-terminal region of TSC1 are important for TSC1 function and for maintaining the activity of the TSC1-TSC2 complex.
A global approach to the management of EMR (Electronic Medical Records) of patients with HIV/AIDS in Sub-Saharan Africa: the experience of DREAM Software
Authors: Nucita Andrea , Bernava Giuseppe M , Bartolo Michelangelo , Masi Fabio Di Pane , Giglio Pietro , Peroni Marco , Pizzimenti Giovanni , Palombi Leonardo
Published: September 2009

Background

The DREAM Project operates within the framework of the national health systems of several sub-Saharan African countries and aims to introduce the essential components of an integrated strategy for the prevention and treatment of HIV/AIDS. The project is intended to serve as a model for a wide-ranging scale-up in the response to the epidemic. This paper aims to show DREAM's challenges and the solutions adopted. One of the solutions is the efficient management of the clinical data regarding the treatment of the patients and epidemiological analyses.

Methods

Specific software for the management of the patients' EMR has been created within the DREAM programme in order to deal with the challenges deriving from the context in which DREAM operates. Setting up a computer infrastructure in health centres, providing a power supply, as well as managing the data and the project resources efficiently and reliably, are some of the questions that have been analysed in this study.

Results

Over the years this software has proved that it is able to respond to the need for efficient management of the clinical data and organization of the health centres. Today it is used in 10 countries in sub-Saharan Africa by thousands of professionals and by now it has reached its fourth version. The medical files of over 73,000 assisted patients are managed by this software and the data collected with it have become essential for the epidemiological research that is carried out to improve the effectiveness of the therapy.

Conclusion

Sub-Saharan Africa is the region hardest hit by HIV and AIDS in the world. However, the resources and responses adopted so far, to confront the epidemic, have at times been rather minimalist. The DREAM project has faced the battle against the epidemic by equipping itself with qualitative standards comparable to Western ones. The experience of DREAM has revealed that it is indeed possible to guarantee levels of excellence in developing countries, also in the sphere of ICT (Information and Communication Technology), thus making the intervention even more effective and contributing to bridging the digital divide.