bluuebunny/crossref_metadata_2025 huggingface dataset:
Tinnitus as an Alarm Bell: Stress Reaction Tinnitus Model
Authors: Alpini D. , Cesarani A.
Published: March 2006

Stress is a significant factor influencing the clinical course of tinnitus. Auditory system is particularly sensitive to the effects of different stress factors (chemical, oxidative, emotional, etc.). Different stages of reaction (alarm, resistance, exhaustion) lead to different characteristics of tinnitus and different therapeutic approaches. Individual characteristics of stress reaction may explain different aspects of tinnitus in various patients with different responses to treatment, despite similar audiological and ethiological factors. A model based on individual reactions to stress factors (stress reaction tinnitus model) could explaintinnitus as an alarm signal, just like an ‘alarm bell’, informing the patient that something potentially dangerous for subject homeostasis is happening. Tinnitus could become a disabling symptom when the subject is chronically exposed to a stress factor and is unable to switch off the alarm. Stress signals, specific for each patient, have to be identified during the ‘alarm’ phase in order to prevent an evolution toward the ‘resistance’ and ‘exhaustion’ phases. In these phases, identification of stressor is no more sufficient, due to the organization of a ‘paradoxical auditory memory’ and a ‘pathologically shifted attention to tinnitus’. Identification of stress reaction phase requires accurate otolaryngology and anamnesis combined with audiological matching tests (Feldman Masking Test, for example) and psychometric questionnaires (Tinnitus Reaction and Tinnitus Cognitive Questionnaires).
Primary and Secondary Auditory Cortex Stimulation for Intractable Tinnitus
Authors: De Ridder Dirk , De Mulder Gert , Verstraeten Edwin , van der Kelen Karolien , Sunaert Stefan , Smits Marion , Kovacs Silvia , Verlooy Jan , Van de Heyning Paul , Moller Aage R.
Published: March 2006

Introduction: Recent research suggests tinnitus is a phantom phenomenon based on hyperactivity of the auditory system, which can be visualized by functional neuroimaging, and transiently modulated by transcranial magnetic stimulation (TMS). We present the results of the first implanted electrodes on the primary and secondary auditory cortex after a successful TMS suppression. Methods and Materials: Twelve patients underwent an auditory cortex implantation, 10 for unilateral and 2 for bilateral tinnitus, based on >50% suppression applying TMS. Results were analyzed for pure tone tinnitus and white noise tinnitus. Results: TMS results in 77% pure tone tinnitus and 67% white noise reduction. Electrical stimulation via an implanted electrode results in a mean of 97% pure tone tinnitus and 24% white noise suppression. Mean Visual Analogue Scale score decreases from 9.5 to 1.5 for pure tone and from 8.8 to 6.8 for white noise postoperatively. Discussion: Pure tone tinnitus might be the conscious percept of focal neuronal hyperactivity of the auditory cortex. Once visualized, this hyperactivity can be modulated by neurostimulation. Conclusion: The preliminary results of the first implantations suggest that patients with unilateral pure tone tinnitus are good surgical candidates for electrode implantation and permanent electrical stimulation of the auditory cortex, provided that the tinnitus is of recent origin and can be suppressed by TMS.
Emotions in Vowel Segments of Continuous Speech: Analysis of the Glottal Flow Using the Normalised Amplitude Quotient
Authors: Airas Matti , Alku Paavo
Published: March 2006

Emotions in short vowel segments of continuous speech were analysed usinginverse filtering and a recently developed glottal flow parameter, the normalisedamplitude quotient (NAQ). Simulated emotion portrayals were produced by 9 professionalstage actors. Separated /a:/ vowel segments were inverse filtered andparameterised using NAQ. Statistical analyses showed significant differencesamong most of the emotions studied. Results also demonstrated clear gender differences.Inverse filtering, together with NAQ, was shown to be a promisingmethod for the analysis of emotional content in continuous speech.
Production of Weak Elements in Speech – Evidence from F₀ Patterns of Neutral Tone in Standard Chinese
Authors: Chen Yiya , Xu Yi
Published: March 2006

Many weak elements in speech, such as schwa in English and neutral tone inStandard Chinese, are commonly assumed to be unspecified or underspecifiedphonologically. The surface phonetic values of these elements are assumed toderive from interpolation between the adjacent phonologically specified elementsor from the spreading of the contextual phonological features. In the present study,we re-evaluate this view by investigating detailed F0 contours of neutral-tone syllablesin Standard Chinese, which are widely accepted as toneless underlyingly. Werecorded sentences containing 0-3 consecutive neutral-tone syllables at twospeaking rates with two focus conditions. Results of the experiment indicate thatneutral-tone syllables do have a target that is independent of the surroundingtones, which is likely to be static and mid. Furthermore, the neutral tone is found tobe different from the full lexical tones in the manner with which the underlyingtonal target is implemented: it is slow and ineffective both in overcoming the influenceof the preceding full lexical tone and in approaching its own target. Applyingthe recently proposed pitch target approximation model, we conclude that theneutral tone differs from the other lexical tones in Standard Chinese not only interms of its mid target, but also in terms of the weak articulatory strength withwhich this target is implemented. Finally, we suggest that this new understandingis potentially applicable to other weak elements in speech.
Measuring Attachment Representation in an fMRI Environment: A Pilot Study
Authors: Buchheim Anna , Erk Susanne , George Carol , Kächele Horst , Ruchsow Martin , Spitzer Manfred , Kircher Tilo , Walter Henrik
Published: March 2006

This exploratory study is the first to examine the neural correlates of attachment status in adults. The study examined the feasibility of assessing attachment narratives in the functional magnetic resonance imaging (fMRI) environment by challenging subjects to tell attachment stories to specific attachment pictures from the Adult Attachment Projective (AAP) while being scanned. We investigated theoretically derived hypotheses regarding predicted differences in the brain activation patterns of individuals whose attachment status was organized (resolved) versus disorganized (unresolved) with respect to attachment trauma (e.g., as associated with loss through death, abuse, threat of abandonment). Adult attachment was assessed using the AAP, a new representational attachment measure that we thought might be suitable for use in the fMRI environment. This measure was used to obtain a preliminary picture of the neural processes associated with the activation of attachment in 11 healthy female adults. Results are reported from a second-level analysis (p < 0.001 uncorrected) and confirm that the AAP is a feasible measure for use in a neuroimaging environment. Cerebral activation during continuous speech yielded results consistent with the literature. Brain activation was demonstrated in expected visual and semantic brain regions. Furthermore, we found that the rate of articulation was positively correlated with activation in the right superior temporal gyrus. The results of theoretically derived attachment hypotheses showed no differences at the chosen level of significance when comparing the ‘all attachment pictures’ effect between both groups (resolved vs. unresolved). More interestingly, we found a significant interaction effect between the sequence of pictures and attachment category. Only the unresolved participants showed increasing activation of medial temporal regions, including the amygdala and the hippocampus, in the course of the AAP task. This pattern was demonstrated especially at the end of the AAP task where the pictures are drawn to portray traumatic situations. We interpret these results as confirming our hypothesis, linking unresolved attachment to emotional dysregulation of the attachment system. These results are discussed in relation to assessing attachment in an fMRI environment and future research in this area.
Eating Disorders and Attitudes in Maltese and Italian Female Students
Authors: Santonastaso Paolo , Scicluna Dorothy , Colombo Giovanni , Zanetti Tatiana , Favaro Angela
Published: March 2006

Background: No study to date has investigated the frequency of eating disorders (ED) in Malta. The aim of the present study was to provide a cross-cultural comparison between Malta and Italy as regards the frequency of ED and problematic eating attitudes among female students. Sampling and Methods: 128 Maltese and 135 Italian female students aged 16–20 were surveyed. Subjects underwent a structured clinical interview and completed some self-reported questionnaires: the Eating Attitudes Test, the Inventory for the Screening of Eating Disorders and the Eating Disorders Examination-Screening Version. Results: The rates of ED are very similar in the two samples with the exception of the frequency of binge eating disorder which is zero in the Italian sample and 4% among Maltese students. Maltese female students weighed significantly more than their Italian counterparts. They also reported more frequent dieting, fear of fatness and experience of low self-esteem related to body shape and weight. Conclusions: Despite the fact that Maltese female students have a greater tendency to be overweight and display more problematic eating and body attitudes, their risk of developing ED, with the exception of binge eating disorder, is similar to that of their Italian counterparts.
Screening for β-Thalassaemia Trait in Anaemic Pregnant Women
Authors: Bencaiova Gabriela , Burkhardt Tilo , Krafft Alexander , Zimmermann Roland
Published: March 2006

Aims: To find a clinically practicable parameter for the identification of β-thalassaemia trait (β-TT) in anaemic pregnant women on the basis of routine use of haematological examination. Methods: During 1998–2002, 304 anaemic pregnant women were observed in anaemia consultation hours. A retrospective study was carried out with the aim of finding a screening method for β-TT in anaemic pregnant women. We compared a sensitivity and a specificity of six different parameters for identification of β-TT. On the basis of a sensitivity and a specificity for each parameter, we calculated Youden’s index, the likelihood ratio and determined the receiver-operating curves. The logistic regression of the variables MCV, MCH and microcytosis was accomplished. Results: The analysis using receiver-operating curves as well as a calculation of Youden’s index showed that the best parameter for screening of β-TT in anaemic pregnant women is MCV ≤75 fl. For differentiation between patients with iron deficiency anaemia (IDA) alone and patients with β-TT and concomitant IDA, microcytosis ≥15% was the most sensitive. By using MCH we identified 100% of patients in the group with β-TT but only 67% of patients in the group with IDA. Conclusion: Our results suggest identification of β-thalassaemia on the basis of quantification of HbA2 in all patients with MCV ≤75 fl and normal iron status.
The Effect of Methodological Differences in the Measurement of Stapes Motion in Live and Cadaver Ears
Authors: Chien Wade , Ravicz Michael E. , Merchant Saumil N. , Rosowski John J.
Published: March 2006

Methodological differences in sound-induced stapes velocity (Vs) measurements in live and cadaveric ears were examined using fresh cadaveric temporal bones. On average, differences in preparation (sectioning the stapedius tendon, removing the facial nerve, and widely opening the facial recess) had statistically insignificant effects on measured Vs. Differences in the achievable measurement angle (with respect to the axis of piston-like stapes motion) had a significant effect on measured Vs below 2 kHz. These results suggest that much if not all of the differences in Vs measurements between live and cadaveric ears can be explained by the differences in measurement angle between the two preparations. Measurement angle was found to have minimal effect on measured Vs above 2 kHz. This demonstrates that the commonly used method of estimating stapes translational velocity by dividing the measured velocity by the cosine of the measurement angle is not valid above 2 kHz.
Urinary Incontinence in a Group of Primiparous Women in the Czech Republic
Authors: Sottner O. , Zahumensky J. , Krcmar M. , Brtnicka H. , Kolarik D. , Driak D. , Halaska M.
Published: March 2006

Background/Aim: Not only the process of childbirth itself, but also processes during pregnancy seem to be strongly associated with urinary incontinence (UI). According to some epidemiological studies, UI during pregnancy occurs in 23–70% of the pregnant women. These studies also documented some risk factors (e.g., race, age, or body mass index). The aim of our study was to explore the prevalence of UI during pregnancy in the Czech Republic. Methods: 474 primiparas who gave birth at our maternity ward from June 14, 2004, through January 31, 2005, received a questionnaire. The questionnaire concentrated on the occurrence and presentation of UI before and during pregnancy . Results: 339 women (72%) completed the questionnaire. UI and the length of pregnancy are significantly related. We found a baseline UI prevalence before pregnancy of 17%, but before delivery one of 64%. We did not find any statistically significant relation between the prevalence of UI during pregnancy and body mass index before pregnancy as well as before delivery, weight gain during pregnancy, age, and birth weight. Conclusion: Our results show that pregnancy is a risk factor for the development of UI.
Immediate Hypersensitivity to Rifampicin in 3 Patients: Diagnostic Procedures and Induction of Clinical Tolerance
Authors: Buergin Stephan , Scherer Kathrin , Häusermann Peter , Bircher Andreas J.
Published: March 2006

Background: Desensitization with drugs may be indicated in some clinical situations. Apart from large experiences with β-lactam antibiotics and cotrimoxazole in HIV infection, experience with other drugs is limited. Rifampicin may elicit exanthema and urticaria, and their pathomechanisms are not known in detail. Since therapy with rifampicin may be indispensable in mycobacterial infections or against multiresistant Staphylococcusaureus, desensitization may be indicated in some patients. Objective: Report of immediate hypersensitivity to rifampicin and description of diagnostic and desensitization procedures. Methods: We report 3 patients with immediate urticarial reactions to rifampicin. Diagnostic procedures included skin and in vitro tests (specific IgE, lymphocyte transformation test, LTT, and CAST®). The non-irritant cutoff concentration was evaluated in 24 volunteers. A 7-day desensitization procedure was used. Results: Only intradermal tests at a dilution of at least 1:10,000 (concentration of rifampicin approximately 0.006 mg/ml) were true positive, whereas in vitro tests (IgE, LTT and CAST) did not correctly identify hypersensitive patients. Two patients had positive accidental reexposure. All patients were successfully desensitized with rifampicin according to a slow 7-day protocol. Conclusions: Rifampicin rarely elicits immediate hypersensitivity symptoms which may be diagnosed by intradermal skin tests. In vitro tests did not contribute to the diagnosis. Therefore, an IgE-mediated mechanism remains to be proven. Desensitization with rifampicin using different protocols has been reported. In our 3 cases, clinical tolerance to rifampicin was achieved using a 7-day protocol.
Oculogyric Dystonic Reaction to Escitalopram with Features of Anaphylaxis Including Response to Epinephrine
Authors: Patel Ojas P. , Simon Michael R.
Published: March 2006

Dystonia-associated features of anaphylaxis, including tongue swelling, and chest and throat tightness, have been rarely reported with selective serotonin reuptake inhibitor (SSRI) use. The patient is a 44-year-old woman who presented with palpitations, diaphoresis, dyspnea, swelling of the lips and tongue, and fixed upward deviation of her right eye following inadvertent ingestion of 20 mg of escitalopram in addition to her usual 10-mg dose. She reported transient resolution of all symptoms after autoinjector aqueous epinephrine administration (0.3 mg), with recurrence of symptoms after 35 min. The patient presented with one prior episode of anaphylactic symptoms and dystonia. She also reported one episode with purely anaphylactic features of swelling of lips and tongue, difficulty breathing and syncope. This case represents a unique dose-dependent episode of escitalopram-associated oculogyric dystonia with anaphylactic features. The transient resolution of the associated features of dystonia with intramuscular epinephrine administration is unique and suggests a common pathophysiology of the dystonic and anaphylactic symptoms.
Kruppel-Like Factor 2 Inhibits Protease Activated Receptor-1 Expression and Thrombin-Mediated Endothelial Activation
Authors: Lin Zhiyong , Hamik Anne , Jain Rajan , Kumar Ajay , Jain Mukesh K.
Published: March 2006

Objective—

The serine protease thrombin can dramatically alter endothelial gene expression in a manner that confers a proinflammatory phenotype. Recent studies have identified the Kruppel-like factor 2 (KLF2) as a critical regulator of endothelial gene expression. Herein, we provide evidence that KLF2 inhibits thrombin-mediated endothelial activation via alterations in expression of its principal receptor protease-activated receptor-1 (PAR-1).

Methods and Results—

Forced expression of KLF2 in human umbilical vein endothelial cells potently inhibited the ability of thrombin to induce multiple prothrombotic factors (tissue factor, CD40L, plasminogen activator inhibitor-1), cytokines/chemokines (eg, monocyte chemotactic protein-1, interleukin-6 [IL-6], IL-8), and matrix degrading enzymes (eg, matrix metalloproteinases 1, 2, and 9). Mechanistically, KLF2 inhibits PAR-1 expression and, as a consequence, thrombin-mediated nuclear factor κB (NF-κB) nuclear accumulation and DNA binding. Conversely, small interfering RNA–mediated knockdown of KLF2 increases PAR-1 expression and thrombin-mediated induction of NF-κB activation.

Conclusion—

These studies identify KLF2 as a novel regulator of PAR-1 expression and thrombin action in endothelial cells.
Functional Relevance of Golgi- and Plasma Membrane-Localized Endothelial NO Synthase in Reconstituted Endothelial Cells
Authors: Zhang Qian , Church Jarrod E. , Jagnandan Davin , Catravas John D. , Sessa William C. , Fulton David
Published: March 2006

Objective—We have previously shown in COS-7 cells that targeting of endothelial NO synthase (eNOS) to the Golgi or plasma membrane (PM) regulates the mechanism and degree of eNOS activation. However, little is known about the functional significance of eNOS targeting in endothelial cells (ECs). The goal of the current study was to isolate these 2 pools of enzyme in ECs and determine their functional significance in response to agonist stimulation and manipulation of membrane cholesterol levels.

Methods and Results—Using an RNA interference strategy, we generated stable populations of ECs that had >90% inhibition of eNOS expression and lacked the ability to produce NO. Reconstitution of these eNOS “knockdown” ECs with Golgi- and PM-targeted eNOS restored the ability of ECs to produce NO. Calcium-dependent agonists were the more efficient stimulus for the PM-restricted eNOS in ECs. In contrast, Golgi eNOS was less responsive to both calcium- and Akt-dependent agonists. eNOS restricted to the PM was more sensitive to manipulation of membrane cholesterol levels and was significantly attenuated by modified low-density lipoprotein.

Conclusions—Within ECs, the PM is the most efficient location to produce NO but is more vulnerable to cholesterol levels and modified low-density lipoprotein.
Selective Cyclooxygenase-2 Inhibition With Celecoxib Decreases Angiotensin II-Induced Abdominal Aortic Aneurysm Formation in Mice
Authors: King Victoria L. , Trivedi Darshini B. , Gitlin Jonathan M. , Loftin Charles D.
Published: March 2006

Objective—

Inflammation plays an integral role in the development of abdominal aortic aneurysms (AAAs), and the expression of cyclooxygenase (COX)-2 is increased in aneurysmal tissue compared with normal aorta. Nonsteroidal anti-inflammatory drugs, which inhibit the activity of COX-1 and COX-2, decrease AAA expansion in humans and animal models of the disease. In the current study, we investigated the effectiveness of selective inhibition of COX-1 or COX-2 in attenuating AAA formation.

Methods and Results—

Eight-week-old male apolipoprotein E-deficient mice were treated with selective inhibitors of COX-1 or COX-2, SC-560 (≈25 mg · kg
−1
· day
−1
), or celecoxib (≈125 mg · kg
−1
· day
−1
), respectively. COX inhibitors were administered 1 week before angiotensin II (Ang II; 1000 ng · kg
−1
· min
−1
) or saline infusion and throughout the time course of the experiment. COX-1 inhibition had no effect on incidence (control: 90% [9:10] versus SC-560: 89% [8:9]) or severity of Ang II-induced AAA formation. In contrast, celecoxib decreased the incidence (control: 74% [22:30] versus celecoxib: 11% [2:19];
P
<0.001) and severity (
P
=0.001) of AAA formation. Celecoxib also decreased the incidence and severity of AAAs in nonhyperlipidemic mice.

Conclusions—

COX-2–derived prostanoids play a fundamental role in the development of Ang II-induced AAAs in both hyperlipidemic and nonhyperlipidemic mice.
Proximal to Middle Left Coronary Artery Flow Velocity Ratio, As Assessed Using Color Doppler Echocardiography, Predicts Coronary Artery Atherosclerosis in Mice
Authors: Grönros Julia , Wikström Johannes , Hägg Ulrika , Wandt Birger , Gan Li-ming
Published: March 2006

Background—

We aimed to establish a completely noninvasive technique to assess coronary artery atherosclerosis in living mice using proximal to middle left coronary artery (LCA) velocity ratio as assessed with color Doppler echocardiography (CDE).

Methods and Results—

Three groups of apolipoprotein E/low-density lipoprotein receptor double-knockout (apoE/LDLr dko) mice 10, 40, and 80 weeks of age and 3 additional age-matched groups of C57BL/6 mice were examined under anesthesia. Coronary flow velocity in proximal (V
prox
) and middle part (V
mid
) of LCA was measured using CDE. A 40-MHz ultrasound biomicroscope (UBM) was used to visualize lumen and outer vessel diameter in the proximal LCA. Flow velocity in the proximal LCA increased significantly with age and remained constant in the middle part in the apoE/LDLr dko mice, whereas velocities at both the sites remained unchanged in C57 mice. CDE-assessed flow velocity ratio (V
prox
/V
mid
) increased significantly with age in apoE/LDLr dko mice (
P
=0.0055) and correlated significantly to percentage wall thickness, as assessed by UBM (
P
=0.0044;
r
=0.65) and histology (
P
=0.0002;
r
=0.78). Wall thickness increased with age in the apoE/LDLr dko mice as measured with UBM (
P
=0.0093;
r
=0.49), which was also confirmed with histology (
P
<0.0001;
r
=0.73).

Conclusions—

CDE and UBM are useful noninvasive tools to quantify mouse coronary artery atherosclerosis in vivo.
Cardiac-Specific Deletion of
Gata4
Reveals Its Requirement for Hypertrophy, Compensation, and Myocyte Viability
Authors: Oka Toru , Maillet Marjorie , Watt Alistair J. , Schwartz Robert J. , Aronow Bruce J. , Duncan Stephen A. , Molkentin Jeffery D.
Published: March 2006

The transcription factor GATA4 is a critical regulator of cardiac gene expression where it controls embryonic development, cardiomyocyte differentiation, and stress responsiveness of the adult heart. Traditional deletion of
Gata4
caused embryonic lethality associated with endoderm defects and cardiac malformations, precluding an analysis of the role of GATA4 in the adult myocardium. To address the function of GATA4 in the adult heart,
Gata4-loxP
–targeted mice (
Gata4fl/fl
) were crossed with mice containing a β-myosin heavy chain (β-MHC) or α-MHC promoter-driven Cre transgene, which produced viable mice that survived into adulthood despite a 95% and 70% loss of GATA4 protein, respectively. However, cardiac-specific deletion of
Gata4
resulted in a progressive and dosage-dependent deterioration in cardiac function and dilation in adulthood. Moreover, pressure overload stimulation induced rapid decompensation and heart failure in cardiac-specific
Gata4
-deleted mice. More provocatively,
Gata4
-deleted mice were compromised in their ability to hypertrophy following pressure overload or exercise stimulation. Mechanistically, cardiac-specific deletion of
Gata4
increased cardiomyocyte TUNEL at baseline in embryos and adults as they aged, as well as dramatically increased TUNEL following pressure overload stimulation. Examination of gene expression profiles in the heart revealed a number of profound alterations in known GATA4-regulated structural genes as well as genes with apoptotic implications. Thus, GATA4 is a necessary regulator of cardiac gene expression, hypertrophy, stress-compensation, and myocyte viability.
N-3 Fatty Acids Inhibit Vascular Calcification Via the p38-Mitogen-Activated Protein Kinase and Peroxisome Proliferator-Activated Receptor-γ Pathways
Authors: Abedin M. , Lim J. , Tang T.B. , Park D. , Demer L.L. , Tintut Y.
Published: March 2006

Fish oil supplementation is associated with lower risk of coronary artery disease in humans, and it has been shown to reduce ectopic calcification in an animal model. However, whether N-3 fatty acids, active ingredients of fish oil, have direct effects on calcification of vascular cells is not clear. In this report, we investigated the effects of eicosapentaenoic acid and docosahexaenoic acid (DHA) on osteoblastic differentiation and mineralization of calcifying vascular cells (CVCs), a subpopulation of bovine aortic medial cells that undergo osteoblastic differentiation and form calcified matrix in vitro. Results showed that N-3 fatty acids inhibited alkaline phosphatase (ALP) activity and mineralization of vascular cells, suggesting that they directly affect osteoblastic differentiation in vascular cells. By Western blot analysis, DHA activated p38-mitogen-activated protein kinase (MAPK) but not extracellular-regulated kinase (ERK) or Akt. An inhibitor of p38-MAPK partially reversed the inhibitory effects of DHA on osteoblastic differentiation and mineralization. Transient transfection experiments showed that DHA also activated peroxisome proliferator-activated receptor-γ (PPAR-γ). Both p38-MAPK activator and PPAR-γ agonists reproduced the inhibitory effects of DHA on CVC mineralization. Pretreatment with DHA also inhibited interleukin-6–induced ALP activity and mineralization. Together, these results suggest that N-3 fatty acids directly inhibit vascular calcification, and that the inhibitory effects are mediated by the p38-MAPK and PPAR-γ pathways.
α-Galactosidase A Deficiency Leads to Increased Tissue Fibrin Deposition and Thrombosis in Mice Homozygous for the Factor V Leiden Mutation
Authors: Shen Yuechun , Bodary Peter F. , Vargas Fernando B. , Homeister Jonathon W. , Gordon David , Ostenso Kristen A. , Shayman James A. , Eitzman Daniel T.
Published: March 2006

Background—

Factor V Leiden (FVL) is a common genetic risk factor for vascular thrombosis in humans. Fabry disease, an X-linked lysosomal storage disorder attributable to α-galactosidase A (GLA) deficiency, is associated with premature vascular events that may be thrombotic in nature.

Methods and Results—

To examine a potential interaction between
FvL
and
Gla
deficiency in vivo, we analyzed tissue fibrin deposition in mice carrying combined mutations in
FvL
and
Gla
.
Gla
deficiency markedly increased tissue fibrin deposition in mice carrying the
FvL
mutation (0.33±0.03%; n=7) compared with
FvL
mutation (0.14±0.02%; n=10;
P
<0.0005).

Conclusions—

These observations demonstrate a synergistic interaction between
Gla
deficiency and
FvL
toward tissue fibrin deposition in mice. Concomitant mutations in these genes may increase the penetrance of vascular thrombotic events in humans.
Rapid Hypoxia Preconditioning Protects Cortical Neurons From Glutamate Toxicity Through δ-Opioid Receptor
Authors: Zhang Junhui , Qian Hong , Zhao Peng , Hong Soon-Sun , Xia Ying
Published: March 2006

Background and Purpose—

Hypoxia preconditioning (HPC), rapid or delayed, has been reported to induce neuroprotection against subsequent severe stress. Because δ-opioid receptor (DOR) plays an important role in delayed HPC-induced neuroprotection against severe hypoxic injury, we asked whether DOR is also involved in the rapid HPC-induced neuroprotection.

Methods—

Cultured rat cortical neurons at culture days 8 to 9 were exposed to a short-term hypoxia (1% O
2
for 30 minutes) to induce HPC followed by 30-minute normoxia before exposing to glutamate toxicity (100 μmol/L; 4 hours). Neuronal viability was assessed by lactate dehydrogenase leakage and morphological assessment. Protein and mRNA levels of DOR were detected by receptor binding and RT-PCR, respectively. Naltrindole was used to block DOR. Developmental changes in NMDA receptor expression was measured by Western blots.

Results—

HPC significantly reduced the glutamate-induced neuronal injury. Receptor binding showed that HPC increased DADLE (a DOR ligand) binding density in the cultured cortical neurons by >90% over control level (
P
<0.05), although RT-PCR did not detect any appreciable change in DOR mRNA. DOR inhibition with naltrindole had no effect on neuronal injury and completely abolished the HPC-induced neuroprotection. In contrast to HPC-induced increase in DADLE binding density, prolonged hypoxia caused severe neuronal injury with a significant decrease in DADLE binding density and DOR mRNA level.

Conclusions—

DOR is involved in neuroprotection induced by rapid HPC in cortical neurons.
A Placebo-Controlled Trial of Constraint-Induced Movement Therapy for Upper Extremity After Stroke
Authors: Taub Edward , Uswatte Gitendra , King Danna Kay , Morris David , Crago Jean E. , Chatterjee Anjan
Published: March 2006

Background and Purpose—

Constraint-Induced Movement therapy (CI therapy) is a neurorehabilitation technique developed to improve use of the more affected upper extremity after stroke. A number of studies have reported positive effects for this intervention, but an experiment with a credible placebo control group has not yet been published.

Methods—

We conducted a placebo-controlled trial of CI therapy in patients with mild to moderate chronic (mean=4.5 years after stroke) motor deficit after stroke. The CI therapy group received intensive training (shaping) of the more affected upper extremity for 6 hours per day on 10 consecutive weekdays, restraint of the less affected extremity for a target of 90% of waking hours during the 2-week treatment period, and application of a number of other techniques designed to produce transfer to the life situation. The placebo group received a program of physical fitness, cognitive, and relaxation exercises for the same length of time and with the same amount of therapist interaction as the experimental group.

Results—

After CI therapy, patients showed large (Wolf Motor Function Test) to very large improvements in the functional use of their more affected arm in their daily lives (Motor Activity Log;
P
<0.0001). The changes persisted over the 2 years tested. Placebo subjects showed no significant changes.

Conclusion—

The results support the efficacy of CI therapy for rehabilitating upper extremity motor function in patients with chronic stroke.
Time to Admission in Acute Ischemic Stroke and Transient Ischemic Attack
Authors: Agyeman Osei , Nedeltchev Krassen , Arnold Marcel , Fischer Urs , Remonda Luca , Isenegger Joerg , Schroth Gerhard , Mattle Heinrich P.
Published: March 2006

Background and Purpose—

The effect of thrombolysis depends on the time from stroke onset to treatment and therefore also on the time when patients come to the hospital. This study was designed to analyze the variables that influence the time from symptom onset to admission (TTA) to the stroke unit.

Methods—

We evaluated the medical records of 615 consecutive stroke or transient ischemic attack (TIA) patients admitted to our neurological department within 48 hours after symptom onset.

Results—

The median TTA was 180 minutes. Referral by emergency medical services (EMS;
P
<0.001), high National Institutes of Health Stroke Scale (NIHSS) scores (
P
<0.001), strokes in the carotid territory (
P
<0.001), and strokes not attributable to small vessel disease (
P
<0.001) were associated with shorter prehospital delays. The TTA was adjusted for travel times (adjTTA), and all these variables remained significantly associated with time to admission. In addition, patients with previous experience with stroke or TIA had longer adjTTA (
P
=0.028). Regression analysis confirmed the independent association between referral by EMS (
P
=0.010), high NIHSS scores (
P
<0.001), carotid territory stroke (
P
<0.001), and first-ever cerebrovascular event (
P
=0.022) with shorter adjTTA.

Conclusions—

Factors such as NIHSS scores and stroke location influence the time to admission but, unlike referral pathways, cannot be modified. Educational programs and stroke campaigns should therefore not only teach typical and less common stroke symptoms and signs but also that EMS provides the fastest means of transportation to a stroke unit and the best chances to get treatment early.
A Novel Neuroprotectant Granulocyte-Colony Stimulating Factor
Authors: Solaroglu Ihsan , Cahill Julian , Jadhav Vikram , Zhang John H.
Published: March 2006

Background and Purpose—

Granulocyte-colony stimulating factor (G-CSF) is a growth factor that orchestrates the proliferation, differentiation, and survival of hematopoietic progenitor cells. It has been used for many years in clinical practice to accelerate the recovery of patients from neutropenia after cytotoxic therapy. However, there is a growing body of evidence from experimental studies suggesting that G-CSF also has important nonhematopoietic functions in the central nervous system.

Summary of Review—

The presence of the G-CSF/G-CSF–receptor system in the brain and its role in neuroprotection and neural tissue repair has been investigated in many recent studies. The neuroprotective actions of G-CSF have mainly been attributed to its anti-inflammatory and antiapoptotic effects. Furthermore, it induces neurogenesis and angiogenesis and improves functional recovery. In this review, we summarize the role of G-CSF and the corresponding signal transduction pathways regulated by G-CSF in neuroprotection.

Conclusions—

Much additional work is needed to better understand the precise mechanisms of G-CSF–induced neuroprotection. However, there is emerging data suggesting that G-CSF is a potential new agent for neuroprotection.
Interferon-β Fails to Protect in a Model of Transient Focal Stroke
Authors: Maier Carolina M. , Yu Fengshan , Nishi Tatsuro , Lathrop Stephanie J. , Chan Pak H.
Published: March 2006

Background and Purpose—

Compelling evidence supporting the role of inflammation in the development of cerebral infarction has focused attention on the potential of antiinflammatory treatment strategies for stroke. Interferon (IFN)-β, an immunomodulatory agent approved for treatment of multiple sclerosis, is being evaluated in a phase I clinical trial in acute ischemic stroke. In the present study, we evaluated the effects of wild-type rat IFN-β and its pegylated counterpart (PEG-IFN-β) in a model of focal ischemia and reperfusion.

Methods—

After 60 minutes of middle cerebral artery occlusion, rats (n=12/group) were treated with IV tail injections of 8 or 16 μg of IFN-β in 300 μL of PBS once daily for 3 or 7 days or with IV or SC injections of PEG-IFN-β for 1 day. The animals were assessed daily for weight and for neurological findings. Additional animals underwent complete hematology and chemistry profiles, as well as complete multiorgan necropsy studies. All of the brain tissue was evaluated for assessment of infarct areas, neutrophil infiltration, and presence of hemorrhagic transformations.

Results—

IFN-β and PEG-IFN-β failed to protect against experimental ischemic brain injury as assessed by histopathology and neurological outcome. Furthermore, IFN-β treatment was associated with significant weight loss and alterations in hematology and chemistry profiles.

Conclusions—

Our results suggest that additional preclinical studies are warranted.
Knowledge About Risk Factors for Stroke
Authors: Müller-Nordhorn Jacqueline , Nolte Christian H. , Rossnagel Karin , Jungehülsing Gerhard J. , Reich Andreas , Roll Stephanie , Villringer Arno , Willich Stefan N.
Published: March 2006

Background and Purpose—

Increased knowledge of stroke risk factors in the general population may lead to improved prevention of stroke. The objective of the present study was to assess knowledge of stroke risk factors and to determine factors associated with knowledge.

Methods—

In a population-based survey, we sent a questionnaire to randomly selected residents in Berlin who were ≥50 years of age enquiring about knowledge of stroke risk factors. Knowledge was assessed in an open-ended question. In addition, we enquired about the source of participants’ information. Sociodemographic factors, including age, sex, educational level, and nationality, were also assessed.

Results—

A total of 28 090 of 75 720 residents (response rate, 37%) responded to the questionnaire. Of all respondents, 68% were able to name ≥1 correct stroke risk factor, and 13% named 4 correct risk factors. The majority of respondents named mass media as source of information (82%), followed by family/friends (45%) and by general physicians (20%). In multivariable analysis, increased knowledge of stroke risk factors was significantly associated with younger age, a higher educational level, not living alone, a German nationality, and having received any information about stroke during the last year. However, characteristics of respondents using the respective sources of information varied significantly.

Conclusions—

Mass media was most frequently named as a source of information about stroke risk factors. Source of information used varied according to population characteristics. Health education programs should take this into account and be adapted accordingly.
Observed and Modeled Greenland Ice Sheet Snow Accumulation, 1958–2003, and Links with Regional Climate Forcing
Authors: Hanna Edward , McConnell Joe , Das Sarah , Cappelen John , Stephens Ag
Published: March 2006

Annual and monthly snow accumulation for the Greenland Ice Sheet was derived from ECMWF forecasts [mainly 40-yr ECMWR Re-Analysis (ERA-40)] and further meteorological modeling. Modeled accumulation was validated using 58 ice core accumulation datasets across the ice sheet and was found to be 95% of the observed accumulation on average, with a mean correlation of 0.53 between modeled and observed. Many of the ice core datasets are new and are presented here for the first time. Central and northern interior parts of the ice sheet were found to be ∼10%–30% too dry in ERA-40, in line with earlier ECMWF analysis, although too much (>50% locally) snow accumulation was modeled for interior southern parts of Greenland. Nevertheless, 47 of 58 sites show significant correlation in temporal variability of modeled with observed accumulation. The model also captures the absolute amount of snow accumulation at several sites, most notably Das1 and Das2 in southeast Greenland. Mean modeled accumulation over the ice sheet was 0.279 (standard deviation 0.034) m yr−1 for 1958–2003 with no significant trend for either the ice sheet or any of the core sites. Unusually high accumulation in southeast Greenland in 2002/03 leads the authors to study meteorological synoptic forcing patterns and comment on the prospect of enhanced climate variability leading to more such events as a result of global warming. There is good agreement between precipitation measured at coastal meteorological stations in southern Greenland and accumulation modeled for adjacent regions of the ice sheet. There is no significant persistent relation between the North Atlantic Oscillation index and whole or southern Greenland accumulation.
Recent Trends in Four Common Stability Indices Derived from U.S. Radiosonde Observations
Authors: DeRubertis Diana
Published: March 2006

Daily sounding-derived atmospheric stability indices are typically employed for short-term severe weather forecasts. Over longer time periods, these indicators may convey changes in the potential for severe storm development over the United States. Daily (0000 UTC) observations from 48 radiosonde stations in the contiguous United States are extracted to assemble a ∼50 yr record of four common stability indices: the Lifted Index, the K-Index, convective available potential energy (CAPE), and the Air Force Severe Weather Threat Index. Because of radiosonde data inhomogeneities, the 1973–97 period is the focus of the analysis. Trends in the mean and extreme values of daily index observations are calculated for spring and summer seasons. In addition, climatological mean indices, as well as the mean frequency of index extremes, are determined for all U.S. regions. At stations free of obvious data discontinuities, the early part of the record (1948–65) is compared with more recent periods.

In spring, few significant changes in either index means or extremes are reported. However, in summer, widespread trends toward enhanced instability appear, particularly in the Lifted Index, the K-Index, and CAPE. Stations in the Plains and southern states show the most consistent increases in severe weather potential, while significant trends in index extremes are uncommon in the western region, possibly due to the rarity of severe weather there.
Variability and the Severity of the “Little Dry Season” in Southwestern Nigeria
Authors: Adejuwon James O. , Odekunle Theophilus O.
Published: March 2006

The Little Dry Season (LDS) of West Africa is manifested as a decline in both the frequency and amount of daily rainfall for a number of weeks halfway through the rainy season. The mean or climatological LDS is derived from the slope of the cumulative percentage graph of 5-day mean rainfall (daily rainfall data between 1961 and 2000). LDS variability analysis was carried out using the concept of relative variability. The results obtained showed that LDS is observed from mid-July to mid-September along the coast. Northward and eastward the period of occurrence decreases. In general, the phenomenon is not observed north of the eastward-flowing or east of the southward-flowing River Niger. The results also show considerable interannual variability. Variability was highest along the southwestern coast and declined inland northward and eastward. Variability was highest with respect to total rainfall, followed by length and number of rain days. There are indications that for most years the LDS was only relatively dry while in certain years it represented a period of drought. The occurrence of the LDS in space and time is explained by the movements of the intertropical discontinuity and its associated zone of rainfall. Interannual variability in occurrence and severity are determined by the Walker Circulation phenomenon. Variability in the severity of the LDS has mixed implications for agricultural practices.
Sea Surface Temperature Daytime Climate Analyses Derived from Aerosol Bias-Corrected Satellite Data
Authors: Nalli Nicholas R. , Reynolds Richard W.
Published: March 2006

This paper describes daytime sea surface temperature (SST) climate analyses derived from 16 years (1985–2000) of reprocessed Advanced Very High Resolution Radiometer (AVHRR) Pathfinder Atmospheres (PATMOS) multichannel radiometric data. Two satellite bias correction methods are employed: the first being an aerosol correction, the second being an in situ correction of satellite biases. The aerosol bias correction is derived from observed statistical relationships between the slant-path aerosol optical depth and AVHRR multichannel SST (MCSST) depressions for elevated levels of tropospheric and stratospheric aerosol. Weekly analyses of SST are produced on a 1° equal-angle grid using optimum interpolation (OI) methodology. Four separate OI analyses are derived based on 1) MCSST without satellite bias correction, 2) MCSST with aerosol satellite bias correction, 3) MCSST with in situ correction of satellite biases, and 4) MCSST with both aerosol and in situ corrections of satellite biases. These analyses are compared against the Tropical Rainfall Measuring Mission (TRMM) Microwave Imager OI SST, along with the extended reconstruction SST in situ analysis product. The OI analysis 1 exhibits significant negative and positive biases. Analysis 2, derived exclusively from satellite data, reduces globally the negative bias associated with elevated atmospheric aerosol, and subsequently reveals pronounced variations in diurnal warming consistent with recently published works. Analyses 3 and 4, derived from in situ correction of satellite biases, alleviate biases (positive and negative) associated with both aerosol and diurnal warming, and also reduce the dispersion. The PATMOS OISST 1985–2000 daytime climate analyses presented here provide a high-resolution (1° weekly) empirical database for studying seasonal and interannual climate processes.
Assessing the Validity of Self-Reports by Gang Members: Results From the Arrestee Drug Abuse Monitoring Program
Authors: Webb Vincent J. , Katz Charles M. , Decker Scott H.
Published: March 2006

Scholars who study criminal and delinquent behavior rely on the self-report method for measuring crime and delinquency. Gang researchers also rely on the self-report method for determining gang involvement and measuring criminal and delinquent behavior of gang members. This study examines disclosure rates of recent drug use by gang members in comparison with their urinalysis outcomes. A substantial body of research indicates that members of the criminally involved population, at least those who get arrested, are less than accurate when reporting recent drug use; however, it does not appear that gang members are different in their reporting than members of the group as a whole. Disclosure rates of gang members did not differ significantly from those of non-gang members. This adds to the cumulative body of evidence that although not perfect, self-reports of illegal behavior are a valid measurement technique in gang research.
A Job Isn’t Just a Job: The Differential Impact of Formal Versus Informal Work on Adolescent Problem Behavior
Authors: Apel Robert , Paternoster Raymond , Bushway Shawn D. , Brame Robert
Published: March 2006

Research consistently demonstrates a positive correlation between hours of employment and problem behavior for adolescents. In response, the National Research Council (1998) proposed limits on youth work involvement, and its recommendation forms the basis for proposed legislation to amend federal child labor provisions. An unanticipated consequence may be to increase the amount of time that youths spend in the informal labor market because child labor laws only govern youth employment in the formal labor market. In this article, the authors attempt to address this policy implication and fill a gap in the extant literature by examining the impact of both formal and informal employment on delinquency and substance use. Because work patterns tend to be very different by gender and race or ethnicity, the authors estimate separate models for these subgroups. The authors use longitudinal data to deal with the possibility that there are unobserved differences between those that work and those that do not.