bluuebunny/crossref_metadata_2025 huggingface dataset:
The four mammalian splice variants encoded by the p21‐activated kinase 3 gene have different biological properties
Authors: Kreis Patricia , Rousseau Véronique , Thévenot Emmanuel , Combeau Gaëlle , Barnier Jean‐Vianney
Published: May 2008

The p21‐activated kinases (PAK1), PAK2, and PAK3 are members of the PAK group I and share high sequence identity and common biochemical properties. PAK3 is specifically implicated in neuronal plasticity and also regulates cell cycle progression, neuronal migration, and apoptosis. Loss of function of PAK3 is responsible for X‐linked non‐syndromic mental retardation whereas gain of PAK3 function is associated with cancer. To understand the functional specificities of PAK3, we analyzed the structure of PAK3 gene products. We report here the characterization of a new alternatively spliced exon called c located upstream of the previously identified exon b. Exon b is detected in all tetrapods and not in fish, exon c is only present in mammals. Mammalian PAK3 genes encode four splice variants and the corresponding proteins were detected with specific antibodies in brain extracts. All PAK3 transcripts are specifically expressed in brain and in particular in neurons. The presence of the exons b and c renders the kinase constitutively active and decreases interaction with GTPases. The expression of the new splice variants in COS7 cells alters cell morphology and modifies the structure of focal adhesions. We propose that the appearance of new alternatively spliced exons during evolution and the resulting increase of complexity of PAK3 gene products may confer new functions to this kinase and contribute to its specific roles in neuronal signaling.
The effect of l‐arginine administration on muscle force and power in postmenopausal women
Authors: Fricke Oliver , Baecker Natalie , Heer Martina , Tutlewski Baerbel , Schoenau Eckhard
Published: May 2008

Previously published data (J Bone Miner Res (2005); 20: 471) did not give evidence that the administration of the nitric oxide precursor l‐arginine increases bone formation and decreases bone resorption in postmenopausal women. Data of this trial were reanalysed for putative effects of l‐arginine on muscle mass and muscular function. Therefore, 11 females of the former study group (n = 15; age 54·5 ± 4·1 years; daily oral administration of 18 g l‐arginine hydrochloride (equivalent of 14·2 g l‐arginine) over 6 months) and 12 females of the control group (n = 15; age 55·3 ± 4·4 years; daily administration of 18 g dextrose over 6 months) were analysed for biomechanical parameters (MIGF, maximal isometric grip force; PJF, peak jump force; PJP, peak jump power) and for the cross‐sectional muscle area (MA) and fat area (FA) at forearm and leg (calf) measured by peripheral quantitative computed tomography. The study was performed in a double‐blind design. The assessment of muscular and biomechanical parameters was undertaken before and after 6 months of l‐arginine versus placebo administration. l‐arginine‐supplemented females had a significant increase of PJF/kg in comparison with the control group. PJP/kg, MIGF, MA and FA were not significantly influenced by the administration of l‐arginine. In conclusion, the administration of l‐arginine increased maximal force in mechanographic analyses and may prevent a decline of muscle force in postmenopausal women.
A Randomized Controlled Trial of Continuous Labor Support for Middle‐Class Couples: Effect on Cesarean Delivery Rates
Authors: McGrath Susan K. , Kennell John H.
Published: May 2008

ABSTRACT:  Background:
Previous randomized controlled studies in several different settings demonstrated the positive effects of continuous labor support by an experienced woman (doula) for low‐income women laboring without the support of family members. The objective of this randomized controlled trial was to examine the perinatal effects of doula support for nulliparous middle‐income women accompanied by a male partner during labor and delivery.
Methods:
Nulliparous women in the third trimester of an uncomplicated pregnancy were enrolled at childbirth education classes in Cleveland, Ohio, from 1988 through 1992. Of the 686 prenatal women recruited, 420 met enrollment criteria and completed the intervention. For the 224 women randomly assigned to the experimental group, a doula arrived shortly after hospital admission and remained throughout labor and delivery. Doula support included close physical proximity, touch, and eye contact with the laboring woman, and teaching, reassurance, and encouragement of the woman and her male partner.
Results:
The doula group had a significantly lower cesarean delivery rate than the control group (13.4% vs 25.0%, p = 0.002), and fewer women in the doula group received epidural analgesia (64.7% vs 76.0%, p = 0.008). Among women with induced labor, those supported by a doula had a lower rate of cesarean delivery than those in the control group (12.5% vs 58.8%, p = 0.007). On questionnaires the day after delivery, 100 percent of couples with doula support rated their experience with the doula positively. Conclusions: For middle‐class women laboring with the support of their male partner, the continuous presence of a doula during labor significantly decreased the likelihood of cesarean delivery and reduced the need for epidural analgesia. Women and their male partners were unequivocal in their positive opinions about laboring with the support of a doula. (BIRTH 35:2 June 2008)
Impact of First Childbirth on Changes in Women’s Preference for Mode of Delivery: Follow‐up of a Longitudinal Observational Study
Authors: Pang Man Wah , Leung Tse Ngong , Lau Tze Kin , Hang Chung Tony Kwok
Published: May 2008

ABSTRACT:  Background:
A woman’s childbirth experience has an influence on her future preferred mode of delivery. This study aimed to identify determinants for women who changed from preferring a planned vaginal birth to an elective cesarean section after their first childbirth.
Methods:
This prospective longitudinal observational study involved two units that provide obstetric care in Hong Kong. A mail survey was sent to 259 women 6 months after their first childbirth. These women had participated in a longitudinal cohort study that examined their preference for elective cesarean section in the antenatal period of their first pregnancies. Univariate and multivariate analyses were performed to identify determinants for women who changed from preferring vaginal birth to elective cesarean section.
Results:
Twenty‐four percent (23.8%, 95% CI 18.4–29.3) of women changed from preferring vaginal birth to elective cesarean section after their first childbirth. Determinants found to be positively associated with this change included actual delivery by elective cesarean section (OR 106.3, 95% CI 14.7–767.4) intrauterine growth restriction (OR 19.5, 95% CI 1.1–353.6), actual delivery by emergency cesarean section (OR 8.4, 95% CI 3.4–20.6), higher family income (OR 3.2, 95% CI 1.1–8.8), use of epidural analgesia (OR 2.6, 95% CI 1.0–6.8), and higher trait anxiety score (OR 1.1, 95% CI 1.0–1.3). The most important reason for women who changed from preferring vaginal birth to elective cesarean section was fear of vaginal birth (24.4%).
Conclusions:
A significant proportion of women changed their preferred mode of delivery after their first childbirth. Apart from reducing the number of cesarean sections in nulliparous women, prompt provision of education to women who had complications and investigations into fear factors during vaginal birth might help in reducing women’s wish to change to elective cesarean section. (BIRTH 35:2 June 2008)
Economic Implications of Home Births and Birth Centers: A Structured Review
Authors: Henderson Jane , Petrou Stavros
Published: May 2008

ABSTRACT: Background:It is widely perceived that home births and birth centers may help decrease the costs of maternity care for women with uncomplicated pregnancies and deliveries. This structured review examines the literature relating to the economic implications of home births and birth center care compared with hospital maternity care.Methods:The bibliographic databases MEDLINE (from 1950), CINAHL (from 1982), EMBASE (from 1980), and an “in‐house” database, Econ2, were searched for relevant English language publications using MeSH and free text terms. Data were extracted with respect to the study design, inclusion criteria, clinical and cost results, and details of what was included in the cost calculations.Results:Eleven studies were included from the United Kingdom, United States, Australia, and Canada. Two studies focused on home births versus other forms and locations of care, whereas nine focused on birth centers versus other forms and locations of care. Resource use was generally lower for women cared for at home and in birth centers due to lower rates of intervention, shorter lengths of stay, or both. However, this fact did not always translate into lower costs because, in the U.K. where many studies were conducted, more midwives of a higher grade were employed to manage the birth centers than are usually employed in maternity units, and because of costs of converting existing facilities into delivery rooms. The quality of much of the literature was poor, although no studies were excluded for this reason. Selection bias was likely to be a problem in those studies not based on randomized controlled trials because, even where birth center eligibility was applied throughout, women who choose to deliver at home or in a birth center are likely to be different in terms of expectations and approach from women choosing to deliver in hospital.Conclusions:This review highlights the paucity of economic literature relating to home births and birth centers. Differences in results between studies may be attributed to differences in health care systems, differences in methods used, and differences in costs included. Further economic research that involves detailed bottom‐up costing of alternative options for place of birth and measures multiple outcomes, including women’s preferences, would help address the question of whether out‐of‐hospital birth is beneficial in economic terms. (BIRTH 35:2 June 2008)
Events after Stillbirth in Relation to Maternal Depressive Symptoms: A Brief Report
Authors: Surkan Pamela J , Rådestad Ingela , Cnattingius Sven , Steineck Gunnar , Dickman Paul W.
Published: May 2008

ABSTRACT:  Background:
Actions taken after a stillbirth can affect long‐term psychological morbidity. Our objective was to study how infant bonding and maternal actions after stillbirth are associated with ensuing depressive symptoms.
Methods:
Using the population‐based Swedish Medical Birth Register, we identified all 380 Swedish‐speaking women who gave birth to singleton stillborn infants in Sweden in 1991. Of these, 314 (83%) completed a postal questionnaire 3 years after the stillbirth. Items included actions taken to bond with the baby and demographics. The association between care‐related factors and later maternal depressive symptoms was quantified using relative risks estimated using multivariable regression.
Results:
We observed an almost sevenfold increased risk of depressive symptoms for mothers who reported not being with their babies as long as they wished (adjusted risk ratio [RR] 6.9, 95% CI 2.4–19.8). Compared with women who became pregnant again within 6 months, those with no later pregnancy were at higher risk of depressive symptoms (adjusted RR 2.8, 95% CI 0.9–8.4). In addition, compared with women who experienced a stillbirth in their first pregnancy, stillbirth occurring with an infant who was third in the birth order was related to a twofold risk of elevated depressive symptoms (adjusted RR 2.2, 95% CI 0.8–6.4). Furthermore, stillbirth occurring in a fourth or later pregnancy was associated with an almost sevenfold risk of depressive symptomatology (adjusted RR 6.7, 95% CI 2.2–20.5). No evidence of an association was found between other care‐related actions and subsequent maternal depressive symptoms.
Conclusions:
Our results suggest that a mother being with the stillborn baby for as long as desired and the birth order of the stillbirth may influence her later depressive symptomatology. Compared with mothers who became pregnant again within 6 months, those who did not have a subsequent pregnancy were at higher risk of depressive symptoms at 3 years’ follow‐up. (BIRTH 35:2 June 2008)
Call‐Fleming Syndrome and Orgasmic Cephalgia
Authors: Keyrouz Salah , Dhar Rajat , Axelrod Yekaterina
Published: June 2008

We report a case of Call‐Fleming syndrome complicating orgasmic thunderclap headache. Recognizing this benign condition that mimics symptoms of subarachnoid hemorrhage prevents unwarranted invasive investigations and interventions that may cause harm.
Analysis of Headache Management in a Busy Emergency Room in the United States
Authors: Sahai‐Srivastava Soma , Desai Prakash , Zheng Ling
Published: June 2008

Objectives.— To analyze the demographics, diagnosis, and treatment patterns in patients with headache‐seeking treatment in one of the busiest emergency rooms (ER) of an academic medical center in the USA.

Background.— The past decade has seen tremendous improvement in acute and preventive management of headaches. However, there are very few data on how headache patients are managed by ER doctors.

Methods.— Retrospective analysis of 100 charts chosen at random for patients with a discharge diagnosis of headache (according to ICD‐9 codes) from the University of Southern California + Los Angeles County Hospital ER.

Results.— The majority of patients were female (74%) and Hispanic (76%) with an age range of 15‐68 years. The most common ER diagnoses were migraine (42%) and headache not otherwise specified (headache NOS – 42%). Fifty‐one percent of patients received a head computerized tomography; 9% received a lumbar puncture. Medications most frequently used for acute treatment, whether migraine or headache NOS, were narcotics (25%), followed by antiemetics (24%), nonsteroidal anti‐inflammatory drugs (19%), and acetaminophen (17%). Only 5% of migraine patients received migraine‐specific triptans in the ER (2% overall). Thirty‐one percent of migraineurs were given a prescription for a triptan upon discharge from the ER (17% of all patients). Eighteen percent of patients were admitted to the hospital with secondary headache. The final diagnosis in the ER matched the diagnosis of the neurologist in 79% of cases with a moderate degree of agreement.

Conclusion.— Narcotics remain the medications most often chosen for treatment of all acute headaches (including migraine) in the ER. There is very little use of migraine‐specific medications in the ER. In addition, neurology consults are underutilized even in an academic setting in the ER. The data suggest a lack of clear standards of care for diagnosis and treatment of headache, especially migraines. Specific guidelines for headache management should be established keeping in mind the unique setting of the ER.
Reflections and Speculations on Refractory Migraine: Why Do Some Patients Fail to Improve With Currently Available Therapies?
Authors: Dodick David W.
Published: June 2008

This review considers current debate surrounding refractory migraine and poses the question, why do some patients fail to improve with currently available therapies?
Neurogenesis in the human hippocampus and its relevance to temporal lobe epilepsies
Authors: Siebzehnrubl Florian A. , Blumcke Ingmar
Published: June 2008

Summary

Ample evidence points to the dentate gyrus as anatomical region for persistent neurogenesis in the adult mammalian brain. This has been confirmed in a variety of animal models under physiological as well as pathophysiological conditions. Notwithstanding, similar experiments are difficult to perform in humans. Postmortem studies demonstrated persisting neurogenesis in the elderly human brain. In addition, neural precursor cells can be isolated from surgical specimens obtained from patients with intractable temporal lobe epilepsy (TLE) and propagated or differentiated into neuronal and glial lineages. It remains a controversial issue, whether epileptic seizures have an effect on or even increase hippocampal neurogenesis in humans. Recent data support the notion that seizures induce neurogenesis in young patients, whereas the capacity of neuronal recruitment and proliferation decreases with age. Animal models of TLE further indicate that these newly generated neurons integrate into epileptogenic networks and contribute to increased seizure susceptibility. However, pathomorphological disturbances within the epileptic hippocampus, such as granule cell dispersion (GCD), may not directly result from compromised neurogenesis. Still, the majority of adult TLE patients present with significant dentate granule cell loss at an end stage of the disease, which relates to severe memory and learning disabilities. In conclusion, surgical specimens obtained from TLE patients represent an important tool to study mechanisms of stem cell recruitment, proliferation and differentiation in the human brain. In addition, increasing availability of surgical specimens opens new avenues to systematically explore disease pathomechanisms in chronic epilepsies.
Homocysteine Levels and Lacunar Brain Infarcts in Elderly Women: The Prospective Population Study of Women in Gothenburg
Authors: Zylberstein Dimitri Edin , Skoog Ingmar , Björkelund Cecilia , Guo Xinxin , Hultén Bodil , Andreasson Lars‐Arne , Palmertz Bo , Thelle Dag S. , Lissner Lauren
Published: June 2008

OBJECTIVES:To examine whether total serum homocysteine (tHcy) in a population‐based sample of middle‐aged women is an independent risk factor for presence of lacunar infarcts (LIs) 24 years later.

DESIGN:Prospective population study, follow‐up time 24 years.

SETTING:Gothenburg, an urban area in western Sweden.

PARTICIPANTS:Five hundred twenty‐six women, 89.6% of the original study sample of the Population Study of Women in Gothenburg, aged 46 to 60 at baseline in 1968/69 and re‐examined at age 70 to 84.

MEASUREMENTS:After 24 years of follow‐up, all subjects underwent a psychiatric examination, and 277 computerized tomography (CT) scans of the brain were performed. Two radiologists assessed LIs and white matter lesions (WMLs). Baseline serum tHcy was analyzed from frozen stored serum samples. Logistic regression analyses were performed controlling for potential confounders such as age and selected cardiovascular risk factors.

RESULTS:Thirty‐four subjects had LIs in 1992 (12.3%). In the full multivariate‐adjusted stepwise model, LIs were associated with elevated tHcy (odds ratio (OR)=1.09, 95% confidence interval (CI)=1.01–1.17 per μmol/L of tHcy increment). Women with tHcy values in the highest tertile were almost three times as likely to have LIs (OR=2.82, 95% CI=1.34–5.93) as were those in the lowest tertile. tHcy was not related to WMLs. Subjects who did not undergo a CT scan did not differ from those who did regarding tHcy or any of the covariates studied.

CONCLUSION:tHcy in middle‐aged women is an independent risk factor for LIs, but not WMLs, as observed using CT later in life.
Anticholinergic Activity of 107 Medications Commonly Used by Older Adults
Authors: Chew Marci L. , Mulsant Benoit H. , Pollock Bruce G. , Lehman Mark E. , Greenspan Andrew , Mahmoud Ramy A. , Kirshner Margaret A. , Sorisio Denise A. , Bies Robert R. , Gharabawi Georges
Published: May 2008

The objective of this study was to measure the anticholinergic activity (AA) of medications commonly used by older adults. A radioreceptor assay was used to investigate the AA of 107 medications. Six clinically relevant concentrations were assessed for each medication. Rodent forebrain and striatum homogenate was used with tritiated quinuclidinyl benzilate. Drug‐free serum was added to medication and atropine standard‐curve samples. For medications that showed detectable AA, average steady‐state peak plasma and serum concentrations (Cmax) in older adults were used to estimate relationships between in vitro dose and AA. All results are reported in pmol/mL of atropine equivalents. At typical doses administered to older adults, amitriptyline, atropine, clozapine, dicyclomine, doxepin, L‐hyoscyamine, thioridazine, and tolterodine demonstrated AA exceeding 15 pmol/mL. Chlorpromazine, diphenhydramine, nortriptyline, olanzapine, oxybutynin, and paroxetine had AA values of 5 to 15 pmol/mL. Citalopram, escitalopram, fluoxetine, lithium, mirtazapine, quetiapine, ranitidine, and temazepam had values less than 5 pmol/mL. Amoxicillin, celecoxib, cephalexin, diazepam, digoxin, diphenoxylate, donepezil, duloxetine, fentanyl, furosemide, hydrocodone, lansoprazole, levofloxacin, metformin, phenytoin, propoxyphene, and topiramate demonstrated AA only at the highest concentrations tested (patients with above‐average Cmax values, who receive higher doses, or are frail may show AA). The remainder of the medications investigated did not demonstrate any AA at the concentrations examined. Psychotropic medications were particularly likely to demonstrate AA. Each of the drug classifications investigated (e.g., antipsychotic, cardiovascular) had at least one medication that demonstrated AA at therapeutic doses. Clinicians can use this information when choosing between equally efficacious medications, as well as in assessing overall anticholinergic burden.
Recurrent Falls and Dual Task–Related Decrease in Walking Speed: Is There a Relationship?
Authors: Beauchet Olivier , Annweiler Cédric , Allali Gilles , Berrut Gilles , Herrmann François R. , Dubost Véronique
Published: May 2008

OBJECTIVES: To determine whether dual task–related changes in walking speed were associated with recurrent falls in frail older adults.

DESIGN: Twelve‐month prospective cohort study.

SETTING: Thirteen senior housing facilities.

PARTICIPANTS: Two hundred thirteen subjects (mean age 84.4±5.5).

MEASUREMENTS: Usual and dual‐tasking walking speeds (m/s) were calculated on a 10‐m straight walkway at baseline. Information on incident falls during the follow‐up year was collected monthly, and participants were divided into three groups based on the occurrence of falls (0, 1, and ≥2). Recurrent falls were defined as two or more falls during the 12‐month follow‐up period.

RESULTS: Twenty subjects (9.4%) were classified as recurrent fallers. The occurrence of recurrent falls was associated with age (crude odds ratio (OR)=1.11, P=.02), number of drugs (crude OR=1.28, P=.002), and walking speed under both walking conditions (crude OR=0.96, P=.002 for usual walking and crude OR=0.60, P=.005 for walking while counting backward). Multiple Poisson regression showed that only walking speed while dual tasking and number of drugs were associated with incident falls (incident rate ratio (IRR)=0.84, P=.045 and IRR=1.10, P=.004).

CONCLUSION: Slower walking speed while counting backward was associated with recurrent falls, suggesting that changes in gait performance while dual tasking might be an inexpensive way of identifying frail older adults prone to falling.
Organized Incessant Atrial Arrhythmias in the Setting of Severe, Isolated Biatrial Scarring
Authors: MASSUMI ALI , RASEKH ABDI , SAEED MOHAMMAD , FLAM SCOTT , CHEONG BENJAMIN , MOJIBIAN HAMID , RAZAVI MEHDI
Published: May 2008

Introduction: Diffuse transmural fibrosis and scarring limited to the area without atrial dilation or significant structural heart or other systemic disease has not been reported. We present three cases of a syndrome characterized by refractory organized atrial arrhythmias, diffuse atrial scarring with electrical silence, and mechanical paralysis in the absence of atrial dilation or any systemic or neurodegenerative disorders.

Methods: Patients referred for electrophysiology study of atrial arrhythmias were included. Electroanatomic mapping with the Carto system (Biosense Webster, Diamond Bar, CA, USA) and magnetic resonance imaging (MRI) with scar sequencing were performed.

Results: There was no family or personal history of cardiac, muscular, or developmental diseases. All patients had organized atrial arrhythmias. Echocardiograms showed atrial standstill with normal atrial and ventricular dimensions. No other structural abnormalities were noted. Carto mapping revealed severe biatrial diffuse scarring. The left atrial (LA) was less affected than the right atrial (RA). MRI findings confirmed biatrial scarring. During tachycardia, islands of dissociated electrical activity could be seen in the right atria. Entrainment mapping was not performed in the atria as high‐output pacing could not capture the atria. Coronary sinus entrainment demonstrated the coronary sinus
(CS) not to be critical to the tachycardia. Ablation was targeted toward channels of low voltage but was not successful in any cases. All required atrioventricular (AV) nodal ablation with pacing.

Conclusion: An association between biatrial cardiomyopathy and scarring with normal atrial dimensions has been described. Since severe scarring has not been reported with organized arrhythmias this may represent a new syndrome.
Quality of ECG Monitoring with a Miniature ECG Recorder
Authors: JANATA ANDREAS , LEMMERT MIGUEL E. , RUSSELL JAMES K. , GEHMAN STACY , FLEISCHHACKL ROMAN , ROBAK OLIVER , PERNICKA ELISABETH , STERZ FRITZ , GORGELS ANTON P.M.
Published: May 2008

Background: Long‐term monitoring of patients at risk of arrhythmias would benefit from a miniaturized device. This study evaluated the quality of electrocardiogram (ECG) signals recorded by a miniaturized ECG recorder.

Methods: ECG data were concurrently recorded with an investigational device (Philips Medical Systems, Seattle, WA, USA) and a Holter recorder from patients with cardiac‐related symptoms at the emergency department of a tertiary care university hospital. The device was attached in one of four locations (L1: below left clavicle, L2: midsternal, L3: below left breast, L4: left anterior axillary line in 5th intercostal space). Selected ECG strips were analyzed for atrial activity, QRS width, and basic rhythm by two physicians. Patients were divided into groups based on their number of strips (A 2–5, B 6–9, C 10–21) for descriptive presentation of the data. For statistical analyses, nonlinear mixed‐effects models were used.

Results: In 90 patients, 574 pairs of strips were analyzed. In L1 (n = 37), agreement between the device and the Holter recorder on presence of P wave was 58–80% in groups A–C and in L2 (n = 28):94–98%, L3 (n = 12):30–72%, and L4 (n = 13):0–70%; on PR interval in L1:58–80%, L2:94–98%, L3:30–62%, and L4:0–70%; on rhythm in L1:56–79%, L2:94–98%, L3:30–62%, and L4:0–70%; on QRS width in L1:86–100%, L2:88–98%, L3:100%, and L4:96–100%. The agreement of L2 in the parameters P wave, PR interval, and rhythm diagnosis was better than in the other locations (P < 0.01).

Conclusions: A miniature ECG monitor provided accurate assessment of atrial beats and rhythm diagnosis at a midsternal location and of QRS width at all locations.
Automatic Determination of Timing Intervals for Upper Limit of Vulnerability Using ICD Electrograms
Authors: SHEHATA MICHAEL , BELK PAUL , KREMERS MARK , SABA SAMIR , CAO JIAN , SWERDLOW CHARLES D
Published: May 2008

Background: Implantable cardioverter defibrillator (ICD) implant testing based on the upper limit of vulnerability, or vulnerability testing, permits assessment of defibrillation safety margins without inducing ventricular fibrillation (VF) in most patients. Vulnerability testing requires that T‐wave shocks be timed at the most vulnerable intervals of the cardiac cycle, defined as intervals at which the strongest shock induces VF. Our goal was to develop and test an automated method to select these timing intervals using ICD intracardiac electrograms (EGMs).

Methods: At ICD implant in 22 patients, we determined the range of the most vulnerable intervals by scanning the T wave with shocks. Simultaneously, EGMs were recorded for 351 pacing sequences used for measurement of timing intervals or T‐wave shocks. EGMs were analyzed off‐line using a novel automated method to identify a stable point near the maximum slope of the T wave in the far‐field (shock) EGM. Fiducial timing points based both on the EGM and on the electrocardiogram (ECG) were used to predict the most vulnerable intervals. We compared the predicted most vulnerable to the measured most vulnerable intervals determined by T‐shock scans.

Results: Automatically determined timing points from EGMs and operator‐determined timing points from the surface ECG had comparable accuracy in identifying the measured most vulnerable intervals (91% EGM vs 86% ECG, P = NS).

Conclusions: An automated method based on ICD EGMs identifies the most vulnerable intervals with accuracy comparable to the operator‐performed, clinical method based on the surface ECG. This EGM method can be implemented efficiently in an ICD to automate vulnerability testing.
Biventricular Pacing Attenuates T‐Wave Alternans and T‐Wave Amplitude Compared to Other Pacing Modes
Authors: ANH DAEJOON , SRIVATSA UMA , BUI HANH M , VASCONCELLOS SCOTT , NARAYAN SANJIV M.
Published: May 2008

Background: The impact of altered ventricular activation, including biventricular (BV) pacing, on T‐wave alternans (TWA) and arrhythmic substrates is unclear. We studied how differing ventricular activation sequence alters TWA; the interval from peak‐to‐end of the T‐wave (TpTe) and T‐wave amplitude during right (RV), left (LV), and biventricular (BV) pacing; and right atrial (RA) pacing in patients with preexisting conduction delay.

Methods and Results: We measured TWA during RA, RV, LV, and BV pacing in 33 patients receiving cardiac‐resynchronization‐therapy‐defibrillators. TWA magnitude (Valt) was lower during BV than RV (P < 0.01), RA (P < 0.01), or LV pacing. As a result, BV‐TWA was more often negative than RV‐TWA (P < 0.01), LV‐TWA, and RA‐TWA, particularly when discordant between pacing modes (P < 0.01). Overall, 83% of TWA recordings were abnormal (25% indeterminate), and 17% negative. BV pacing reduced T‐wave amplitude (P < 0.05) and TpTe (P < 0.005) compared to RV pacing and LV pacing (P < 0.05; P < 0.005 respectively). Notably, TWA magnitude varied linearly with T‐wave amplitude for all pacing modes (P < 0.001). Over 410 ± 252 days' follow‐up, RV‐TWA predicted the combined endpoint of death and ICD therapy with 86% negative predictive value (P < 0.05). BV‐TWA, RA‐TWA, and other repolarization indices were not predictive.

Conclusions: BV pacing attenuates TWA in tandem with reduced T‐wave magnitude. In these patients with baseline QRS prolongation, RV‐TWA predicted events more effectively than BV‐TWA and RA‐TWA. Further studies are required to understand how altered ventricular activation influences repolarization dynamics and arrhythmic tendency.
Effects of Scatter Radiation on ICD and CRT Function
Authors: KAPA SURAJ , FONG LUIS , BLACKWELL CHARLES R , HERMAN MICHAEL G. , SCHOMBERG PAULA J , HAYES DAVID L
Published: May 2008

Background: Effects of direct radiation on implantable cardiac devices have been well studied. However, the effects of scatter radiation are not as clear. Recommendations on management of patients with implantable cardiac devices undergoing radiotherapy are based on limited studies mostly involving pacemakers. We sought to elucidate the effects of scatter radiation on implantable cardioverter‐defibrillators (ICDs) and cardiac resynchronization therapy (CRT)‐ICDs.

Methods: We exposed 12 ICDs and eight CRT‐ICDs to 400 cGy of scatter radiation from a 6‐MV photon beam. Devices were programmed with nominal parameters and interrogated prior to radiation, after each fraction, upon completion of the radiation course and again 1 week later. A retrospective review of patients undergoing radiotherapy at the Mayo Clinic–Rochester between 2002 and 2007 in whom the device was outside the radiation field was also performed. There were 13 patients with devices undergoing radiotherapy during this time period, 12 of whom were interrogated prior to and after radiation.

Results: Interrogation reports were reviewed for device reset or parameter changes. There was no evidence of reset or malfunction during or after radiation. Also, no episodes of device reset, inappropriate sensing or therapy, or changes in programmed parameters were found in our review of patients undergoing radiotherapy.

Conclusions: Device reset or malfunction associated with scatter radiation likely represents an unpredictable, rare occurrence. While we see no clear contraindication to radiotherapy in patients with ICDs or CRT‐ICDs, precautions should be taken to avoid direct radiation exposure and to closely evaluate patient outcomes before and after the radiation course.
Extraction of Transvenous Pacing and ICD Leads
Authors: SMITH MACY C , LOVE CHARLES J.
Published: May 2008

The emergence of pacing and implantable cardioverter‐defibrillator (ICD) systems, along with expanding indications of these devices (e.g., cardiac resynchronization therapy and sudden cardiac death prevention), increasing infection rates, and device recalls have created the need for removing and upgrading these systems due to various reasons. Removing the pulse generator of a system is generally uncomplicated. Chronically implanted transvenous leads, however, adhere to the venous endothelium and endocardial tissues over time due to fibrosis. Removal of such leads can be a significantly complex procedure requiring tools and techniques that free the lead at fibrotic binding sites. In this article, the state‐of‐the‐art tools and techniques that provide a systematic approach to consistently and safely extract these devices will be reviewed.
Paroxysmal Atrial Fibrillation Ablation with the Multipolar Mapping and Ablation Catheter (Mesh‐Bard)
Authors: PRATOLA CLAUDIO , NOTARSTEFANO PASQUALE , ARTALE PAOLO , BALDO ELISA , TOSELLI TIZIANO , FERRARI ROBERTO
Published: May 2008

Pulmonary veins (PVs) ablation is a valid treatment option for atrial fibrillation. The standard approach for PVs isolation usually requires two catheters or an electroanatomical reconstruction of the left atrium. We describe our initial experience with a single device for mapping and ablating in a patient referred to our center for the relapsing of atrial fibrillation 3 years after a previous ablation procedure. The newly available catheter MESH was safe and effective to quickly isolate two reconnected PVs.
Incessant Non‐Reentrant Supraventricular Tachycardia Interrupted By Apparent Simultaneous Wenckebach Sequences along Both Nodal Pathways
Authors: MAURY PHILIPPE , HEBRARD AURELIEN , DUPARC ALEXANDRE , FONTAN ANTHONY , ADEGNON KEDI , DELAY MARC
Published: May 2008

We report a new case of non‐reentrant supraventricular tachycardia, associated with tachycardia‐induced cardiomyopathy fully reversible after radiofrequency (RF) ablation, together with striking features of apparent concomitant Mobitz type 1 atrioventricular (AV) block in both AV node pathways. Further analysis of the conduction patterns during the incessant non‐reentrant tachycardia raised unresolved hypothesis about the involved mechanisms and further interrogations on AV node physiology.
Brugada‐Like ST‐Segment Abnormalities Associated with Myocardial Involvement of Hematologic Diseases
Authors: KIM YONG HYUN , LIM HONG EUY , KIM SEONG HWAN , PAK HUI‐NAM , AHN JEONG CHEON , SONG WOO HYUK , KIM YOUNG‐HOON
Published: May 2008

This is a report of Brugada‐like ST‐segment abnormalities related to acute myocarditis associated with hematologic disorders. Electrocardiographic (ECG) pattern of ST‐segment elevation in the right precordial leads mimicking Brugada syndrome may relate to pathological abnormalities due to hematologic disorders that may have genetic, infective, or inflammatory origins. We describe two cases of myocardial involvement of hemotologic disorders, manifested with Brugada‐like ECG findings.
Power and Sample Size Estimation for the Wilcoxon Rank Sum Test with Application to Comparisons of C Statistics from Alternative Prediction Models
Authors: Rosner B. , Glynn R. J.
Published: May 2008

Summary The Wilcoxon Mann‐Whitney (WMW) U test is commonly used in nonparametric two‐group comparisons when the normality of the underlying distribution is questionable. There has been some previous work on estimating power based on this procedure (Lehmann, 1998, Nonparametrics). In this article, we present an approach for estimating type II error, which is applicable to any continuous distribution, and also extend the approach to handle grouped continuous data allowing for ties. We apply these results to obtaining standard errors of the area under the receiver operating characteristic curve (AUROC) for risk‐prediction rules under H1 and for comparing AUROC between competing risk prediction rules applied to the same data set. These results are based on SAS‐callable functions to evaluate the bivariate normal integral and are thus easily implemented with standard software.
Sensitivity Analysis of the Shipboard Integrated Power System
Authors: PREMPRANEERACH PRADYA , HOVER FRANZ S. , TRIANTAFYLLOU MICHAEL S. , MCCOY TIMOTHY J. , CHRYSSOSTOMIDIS CHRYSSOSTOMOS , KARNIADAKIS GEORGE E.
Published: May 2008

Stochastic sensitivity analysis is a valuable tool in ranking inputs and in investigating the degree of interaction of its components. In this paper, we present stochastic simulation results for a shipboard integrated power system and study its sensitivity. Specifically, we apply sensitivity analysis to two high‐fidelity models of shipboard subsystems, investigating open‐ and closed‐loop control of the propulsion system. The results show that different inputs are most important for the open‐ and closed‐loop control, with sensitivities that change dramatically in time as they reflect the transition from the fast electrical scales to slower mechanical scales. We also demonstrate how sensitivity analysis can be used to establish the robustness of the AC drive.
The Art of Successfully Applying Human Systems Integration
Authors: LANDSBURG ALEXANDER C. , AVERY LARRY , BEATON ROBERT , BOST J. ROBERT , COMPERATORE CARLOS , KHANDPUR RAJIV , MALONE THOMAS B. , PARKER CHRISTOPHER , POPKIN STEPHEN , SHERIDAN THOMAS B.
Published: May 2008

This paper reviews developments in human factors and then draws from a number of “best practice” cases in studying how best to apply behavioral science principles, knowledge, and analytical tools to the engineering design or improvement of systems. Government and other commercial experiences are examined with a focus on the Navy human system integration (HSI) process. Included are discussions facilitated at a workshop session sponsored by the Transportation Research Board of the National Academies. There is general consensus that in addition to using a well‐designed or proven process and doing the right things, success is dependent upon attending to a prioritized short list of critical elements. Continued focus on these elements is necessary to successfully apply human behavioral sciences effectively during design, construction, and operation of systems to improve safety, reliability, effectiveness, efficiency, and quality of life.
Trabajo decente. Concepto e indicadores
Authors: GHAI Dharam
Published: May 2008

Actualmente, la finalidad primordial de la OIT es promover oportunidades para que los hombres y las mujeres puedan conseguir un trabajo decente y productivo en condiciones de libertad, equidad, seguridad y dignidad humana (OIT, 1999, pág. 4).
The role of host plant species in the phenotypic differentiation of sympatric populations of Aleiodes nolophanae and Cotesia marginiventris
Authors: Medina Raul F. , Barbosa Pedro
Published: May 2008

The ecology of parasitoids is strongly influenced by their host plant species. Parasitoid fitness can be affected by a variety of plant traits that could promote phenotypic differentiation among populations of parasitoids. Generalist parasitoids are expected to be more affected by plant traits (e.g., plant defensive traits) than specialist parasitoids. Data are presented on phenotypic differences of two braconid parasitoid wasps ovipositing on the same insect host species on two different host plant species. Adult mass, adult longevity, and percent parasitism are compared for the generalist parasitoid Cotesia marginiventris Cresson and the specialist parasitoid Aleiodes nolophanae Ashmead (both Hymenoptera: Braconidae) emerging from green cloverworms, Hypena scabra Fabricius (Lepidoptera: Noctuidae), feeding on two host plant species, alfalfa (Medicago sativa L.) and soybean (Glycine max L. Merr.) (both Fabaceae), at three locations. Specialist wasps that parasitized the green cloverworm on alfalfa had a significantly larger mass than the ones that parasitized the green cloverworm on soybean at the three study sites. Generalist wasps that parasitized green cloverworms on alfalfa had a larger mass than wasps parasitizing green cloverworms on soybean only at one of the study sites (i.e., Prince George's County, MD, USA). Similarly, both specialist and generalist wasps lived longer when parasitizing green cloverworms on alfalfa than when parasitizing them on soybean at only one of the study sites (i.e., Prince George's County). In Prince George's County, percent parasitism on alfalfa by the specialist parasitoid was higher than on soybean for three consecutive years and percent parasitism by the generalist parasitoid was the same on alfalfa and soybean every year. Thus, phenotypic differences among populations associated with different host plant species vary geographically (i.e., parasitoid phenotype associated with different host plant species differ at some sites while it is the same at other sites). The implications of geographic variation for biological control are discussed.
Study of gene expression profile during cord blood‐associated megakaryopoiesis
Authors: Lim Che Kang , Hwang William Y. K. , Aw Swee Eng , Sun Li
Published: May 2008

Aims:  To study the gene profile in cord blood (CB)‐associated megakaryopoiesis.

Methods:  In vitro differentiation of megakaryocytes (Mks) was carried out using human CB CD34+ cells under the stimulation of recombinant human interleukin‐3, stem cell factor and thrombopoietin for 7 d, followed by thrombopoietin only for further 3 d. Lineage‐specific differentiation of Mk was examined by the expression of CD41 using flow cytometry and confocal microscopy. Total cellular RNA was extracted from day‐0 CD34+, day‐10 CD41+ and CD41− populations were isolated by immunomagnetic sorting respectively. Microarray was performed, and the data were analyzed using the GeneChipTM Operating System, Spotfire software and Genomatix BiblioSphere.

Results:  Flow cytometric analysis showed 19.44 ± 3.05% CD41+ cells at day 10 of culture. The purity of CD41+ population was enriched to 95.70 ± 4.19% after sorting. Gene expression profiling revealed an upregulation of 285 and downregulation of 53 unique genes in the CD41+ cells compared with CD41− and CD34+ cells. Platelet‐associated genes, such as thrombospondin 1, platelet glycoprotein IIIa, etc., were highly expressed in CD41+ cells but not in CD41− cells and CD34+ cells. Moreover, some genes that have not been reported to be associated with CB‐derived megakaryopoiesis, such as Cbl‐interacting proteins Sts‐1, protocadherin 21, etc., are found to be highly expressed in the CD41+ cells from this study.

Conclusions:  This study reveals a global gene expression profile of in vitro human CB‐derived megakaryopoiesis at day 10. Some of these genes may play regulatory roles during the development of CB‐derived megakaryopoeisis.
Treatment with testosterone or estradiol in melatonin treated females and males MRL/MpJ‐Faslpr mice induces negative effects in developing systemic lupus erythematosus
Authors: Jimenez‐Caliani Antonio J. , Jimenez‐Jorge Silvia , Molinero Patrocinio , Rubio Amalia , Guerrero Juan M. , Osuna Carmen
Published: May 2008

Abstract:  MRL/MpJ‐Faslpr mice is widely accepted as a valuable model of systemic lupus erythematosus. As described in a previous work, the incidence of lupus in this strain is determined by sex hormones, i.e., estrogens and androgens. Moreover, we reported that the immunomodulatory action of melatonin in these mice was gender‐dependent probably through modulation and inhibition of sex hormones. Herein, we performed an experiment using hormone therapy, by treating female MRL‐lpr mice with testosterone and males with estradiol and with melatonin. A decrease in total serum immunoglobulin (Ig)G and IgM immunoglobulin titers, anti‐double‐stranded DNA, and anti‐CII autoantibodies in female mice treated with both melatonin and testosterone was revealed, along with an increase in pro‐inflammatory cytokines [interleukin (IL)‐2, IL‐6, interferon‐γ, tumor necrosis factor‐α, and IL‐1β), nitrite/nitrate and a decrease in anti‐inflammatory cytokines (IL‐10). Melatonin and estradiol treatment exhibited a similar effect in male mice. Autoantibody titer elevation and pro‐inflammatory versus anti‐inflammatory cytokine prevalence degraded all immunological parameters. Similar results were obtained when spleen and lymph node lymphocytes were cultured. Again, melatonin and testosterone treatment stimulated pro‐inflammatory and reduced anti‐inflammatory cytokines produced by lymphocytes in females. The effect was similar in males treated with melatonin and estradiol. In summary, we observed that although melatonin alone prevents lupus development in females, adding testosterone, increased pro‐inflammatory cytokine pattern. In contrary, estradiol‐treated males did not show any decrease in pro‐inflammatory cytokines but showed an increase in regard to melatonin controls. These findings confirm that melatonin action in MRL/MpJ‐Faslpr mice could be gender‐dependent through modulation of sex hormones.
Estrogen cross‐talk with the melatonin signaling pathway in human osteoblasts derived from adolescent idiopathic scoliosis patients
Authors: Letellier Kareen , Azeddine Bouziane , Parent Stefan , Labelle Hubert , Rompré Pierre H. , Moreau Alain , Moldovan Florina
Published: May 2008

Abstract:  Adolescent idiopathic scoliosis (AIS) represents the most frequently occurring form of scoliosis that occurs and progresses in puberty. This critical period coincides with many biological changes related to estrogens. The aim of this study was to determine the effect of 17‐β‐estradiol on the responsiveness of AIS osteoblasts to melatonin and the cross‐talk between estrogen and melatonin at the levels of the GSα and Giα proteins. Human osteoblasts derived from AIS (n = 40) and control patients (n = 10) were first screened for their functional response to the melatonin and 17‐β‐estradiol. In response to the 17‐β‐estradiol in a specific group of scoliotic patients, the level of 3′,5′‐cyclic adenosine monophosphate (cAMP) was significantly decreased when compared with the level observed in the presence of increasing concentrations of melatonin alone. Ours results provide strong evidence of the cross‐talk between 17‐β‐estradiol and melatonin signaling in human AIS osteoblasts. These results indicate a novel role for 17‐β‐estradiol and melatonin in AIS, controlling the coupling of GSα protein and MT2 receptor on human osteoblasts. We found that the increased cAMP levels induced by melatonin can be corrected by the treatment of the cells with 17‐β‐estradiol. Thus, estrogens or estrogen receptor agonists become important compounds to consider in AIS osteoblast cell functioning. Consequently, our results add a new facet to the understanding the role and function of melatonin in AIS.