bluuebunny/crossref_metadata_2025 huggingface dataset:
Use of preoperative functional MRI to predict verbal memory decline after temporal lobe epilepsy surgery
Authors: Binder Jeffrey R. , Sabsevitz David S. , Swanson Sara J. , Hammeke Thomas A. , Raghavan Manoj , Mueller Wade M.
Published: April 2008

Summary

Purpose: Verbal memory decline is a frequent complication of left anterior temporal lobectomy (L‐ATL). The goal of this study was to determine whether preoperative language mapping using functional magnetic resonance imaging (fMRI) is useful for predicting which patients are likely to experience verbal memory decline after L‐ATL.

Methods: Sixty L‐ATL patients underwent preoperative language mapping with fMRI, preoperative intracarotid amobarbital (Wada) testing for language and memory lateralization, and pre‐ and postoperative neuropsychological testing. Demographic, historical, neuropsychological, and imaging variables were examined for their ability to predict pre‐ to postoperative memory change.

Results: Verbal memory decline occurred in over 30% of patients. Good preoperative performance, late age at onset of epilepsy, left dominance on fMRI, and left dominance on the Wada test were each predictive of memory decline. Preoperative performance and age at onset together accounted for roughly 50% of the variance in memory outcome (p < 0.001), and fMRI explained an additional 10% of this variance (p ≤ 0.003). Neither Wada memory asymmetry nor Wada language asymmetry added additional predictive power beyond these noninvasive measures.

Discussion: Preoperative fMRI is useful for identifying patients at high risk for verbal memory decline prior to L‐ATL surgery. Lateralization of language is correlated with lateralization of verbal memory, whereas Wada memory testing is either insufficiently reliable or insufficiently material‐specific to accurately localize verbal memory processes.
Simultaneous EEG‐fMRI in drug‐naive children with newly diagnosed absence epilepsy
Authors: Moeller Friederike , Siebner Hartwig R. , Wolff Stephan , Muhle Hiltrud , Granert Oliver , Jansen Olav , Stephani Ulrich , Siniatchkin Michael
Published: April 2008

Summary

Purpose: In patients with idiopathic generalized epilepsy (IGE), blood oxygen level dependent (BOLD) EEG during functional MRI (EEG‐fMRI) has been successfully used to link changes in regional neuronal activity to the occurrence of generalized spike‐and‐wave (GSW) discharges. Most EEG‐fMRI studies have been performed on adult patients with long‐standing epilepsy who were on antiepileptic medication. Here, we applied EEG‐fMRI to investigate BOLD signal changes during absence seizures in children with newly diagnosed childhood absence epilepsy (CAE).

Methods: Ten drug‐naive children with newly diagnosed CAE underwent simultaneous EEG‐fMRI. BOLD signal changes associated with ictal EEG activity (i.e., periods of three per second GSW) were analyzed in predefined regions‐of‐interests (ROIs), including the thalamus, the precuneus, and caudate nucleus.

Results: In 6 out of 10 children, EEG recordings showed periods of three per second GSW during fMRI. Three per second GSW were associated with regional BOLD signal decreases in parietal areas, precuneus, and caudate nucleus along with a bilateral increase in the BOLD signal in the medial thalamus. Taking into account the normal delay in the hemodynamic response, temporal analysis showed that the onset of BOLD signal changes coincided with the onset of GSW.

Discussion: In drug‐naive individuals with CAE, ictal three per second GSW are associated with BOLD signal changes in the same striato‐thalamo‐cortical network that changes its regional activity during primary and secondary generalized paroxysms in treated adults. No BOLD signal changes in the striato‐thalamo‐cortical network preceded the onset of three per second GSW in unmediated children with CAE.
Spread of ictal activity in focal epilepsy
Authors: Götz‐Trabert Katrin , Hauck Christoph , Wagner Kathrin , Fauser Susanne , Schulze‐Bonhage Andreas
Published: April 2008

Summary

Purpose: Latencies between seizure onset, propagation of ictal activity, and initial clinical symptoms and signs are critically important for the successful implementation of detection‐based intervention systems in the treatment of epilepsy. This study analyzes intracranial EEG‐recordings for temporal characteristics of ictal spread and its dependence on focus localization.

Methods: Intracerebral EEG recordings of 215 seizures from 43 patients with pharmacoresistant focal epilepsy were evaluated based on site of first propagation, latencies between EEG seizure onset, early propagation, and clinical seizure onset. Seizure onset was mesial temporal in 15 patients, neocortical temporal in 15 patients, and frontal in 13 patients.

Results: Periods during which ictal activity remained confined to the seizure onset area showed significant differences between the patient groups. Median latencies between electrographic seizure onset and early propagation were significantly longer for patients with mesial temporal (5 s in seizure‐based analysis/10 s in patient‐based analysis) as compared to neocortical temporal (3 s/5 s) and frontal seizure focus (1 s/2 s; p < 0.01). Concordantly, median latencies to onset of clinical symptomatology were significantly longer for patients with mesial temporal (17 s/19 s) as compared to neocortical temporal (11 s/17 s) and frontal seizure focus (4 s in seizure‐based analysis and 6 s in patient‐based analysis; p < 0.01).

Conclusions: The speed of propagation of ictal activity and the latencies until initial clinical seizure symptoms differ significantly depending on focus localization. Extended spread often occurred within the time window during which current detection systems operate. This suggests that inclusion criteria of patients suitable for testing the efficacy of detection‐based seizure intervention strategies should be based on focus localization and patient‐individual propagation patterns.
Analysis of the Electrocardiographic Waveforms Produced by Right Ventricular Pacing: Relation to the Nonpaced Patterns
Authors: FRIEDMAN HOWARD S.
Published: April 2008

Background: Ventricular aberrant conduction has a confounding effect on the known relationships between the electrocardiogram (ECG) and left ventricular (LV) mass. By relating the ECG of right ventricular pacing to LV mass and to nonpaced recordings, clarification of these effects might emerge.

Methods and Results: In 30 patients (age, 81 ± 7 years; 13 women) who had right ventricular paced ECGs and echocardiograms, 24 of who also had nonpaced ECGs, comparative analyses were performed. Although the nonpaced ECGs had strong correlations with various echocardiographic measurements, for paced ECGs, only QRS complex voltage and interventricular septal thickness (IVS) were significantly related. However, paced QRS complex voltage relationships correlated with those of nonpaced QRS complexes, ranging from an r = 0.54, P < 0.006, for the sum of the R in aVL and the S in V‐3 to r = 0.78, P < 0.001, for the sum of the R in I and the S in III. Paced ECGs had a QRS complex with a greater spatial amplitude, a longer duration, and a more superior position, and had more deeply inverted T waves than nonpaced ECGs. The differences between the voltages of paced and nonpaced QRS complexes, moreover, diminished as LV mass and/or IVS increased. When compared with nonpaced ECGs, paced ECGs showed the most similarity to nonpaced ECGs having a left bundle branch block (LBBB) pattern. Except for the presence of more superiorly directed QRS complexes, paced impulses were not significantly different (P < 0.008) from nonpaced impulses having a LBBB pattern. Also, the nonpaced ECG pattern had no discernable effect on ECG produced by right ventricular (RV) pacing.

Conclusions: Despite having weak relations with echocardiographic measurements, the QRS complex voltage of the paced ECG correlated with those of nonpaced ECGs, and the voltage differences between them were smaller as LV mass increased.
Intracardiac Echocardiography‐Guided His Bundle Pacing and Atrioventricular Nodal Ablation
Authors: YIN LIXUE , LASKE TIMOTHY G. , RAKOW NANCY , CAI LI , WILLIAMS TERRELL , LI CHUNMEI , ZHAO YONG , DENG YAN , CHEN LIJIAN , LI SHUANG , WANG SHAN , ZHENG CHANGQIONG , LI DEYU , WANG TIANFU , ZHENG YI
Published: April 2008

Background: His bundle pacing (HBP) results in rapid synchronous ventricular activation, but has been associated with long procedure times and compromised pacing and sensing performance. This study sought to reduce procedure time and radiation exposure, and improve electrical performance through more accurate lead placement.

Methods: Intracardiac echocardiography (ICE) was used to guide ablation and lead implantation at the His bundle, right atrial appendage (RAA), and right ventricular apex (RVA), and to assess cardiac function. Custom bipolar screw‐in leads with steerable delivery sheaths and an ablation catheter were navigated using ICE (local detailed imaging) and fluoroscopy (global imaging) in anesthetized closed‐chest canines (N = 6).

Results: HBP (N = 1) or His + ventricular septal pacing (N = 5) was achieved in all canines. The QRS width was 59.7 ± 5.3 ms for canines in sinus rhythm (SR) and 82.8 ± 16.6 ms for canines with HBP (P = 0.0086). The QRS width for RVA pacing was 106.3 ± 18.4 ms (P = 0.042 vs HBP; P = 0.00013 vs SR). HBP thresholds were 3.0 ± 1.0 volts at 0.5 ms (N = 5 due to a late exit block in one canine). The average procedure duration for His lead placement was 40 ± 28 minutes (range of 3–81 minutes) and the total procedural X‐ray exposure was 12 ± 12 minutes (range of 2–30 minutes). Hemodynamic performance was similar for HBP and RAA pacing.

Conclusions: Feasibility of ICE guidance for His pacing and precision ablation of the atrioventricular (AV) node has been shown. This anatomic approach improved accuracy, limited X‐ray exposure, and might allow His pacing in patients with preexisting AV nodal block.
Lead‐Associated Endocarditis: The Important Role of Methicillin‐Resistant Staphylococcus aureus
Authors: GREENSPON ARNOLD J. , RHIM EUGENE S. , MARK GEORGE , DESIMONE JOSEPH , HO REGINALD T.
Published: April 2008

Background: Infection is a potentially life‐threatening complication of cardiac device implantation. Lead‐associated endocarditis (LAE) may be the most serious complication since it is associated with a high mortality.

Methods: The medical records of patients referred to our institution for the treatment of LAE between 1999 and 2007 were reviewed.

Results: A total of 51 of 107 patients referred for device‐related infections met the criteria for LAE. Of these, 19 occurred within 6 months of their most recent procedure (early), while the remaining 32 occurred more than 6 months later (mean = 31.9 months post procedure). Devices included pacemakers in 33 patients and ICDs in 18 patients. The most common organism responsible for infection was Staphylococcus aureus (S. aureus) followed by coagulase‐negative staphylocci (22%) and streptococci (12%). Methicillin‐resistant S. aureus (MRSA) accounted for 67% of the S. aureus infections. Coagulase‐negative staphylococci were responsible for only 26% of early and 19% of late cases. A distant site of infection was common (26/51 = 51%), particularly in patients with MRSA LAE. The device and leads were removed percutaneously in all patients. Only one patient failed to respond to intravenous antibiotics.

Conclusions: Our data suggest that methicillin‐resistant S. aureus is an important pathogen in LAE. Since many infections occur months after the last device procedure, hematogenous spread of organisms from a distant site may be an important contributing factor. These data suggest that strategies to prevent hematogenous infection, particularly with S. aureus, are critical in patients with implantable cardiac devices.
Deactivating Implanted Cardiac Devices in Terminally Ill Patients: Practices and Attitudes
Authors: MUELLER PAUL S. , JENKINS SARAH M. , BRAMSTEDT KATRINA A. , HAYES DAVID L.
Published: April 2008

Background:Clinicians may receive requests to deactivate pacemakers and implantable cardioverter‐defibrillators (ICDs) in terminally ill patients.

Methods:We describe practices and attitudes regarding deactivation of pacemakers and ICDs in terminally ill patients among physicians, nurses, and others who manage treatment of patients with implanted cardiac devices and among field representatives of device manufacturers. A Web‐based survey was provided to Heart Rhythm Society members and to representatives of two manufacturers of implantable cardiac devices. Measurements were the answers of 787 respondents.

Results:Of the respondents, 86.8% reported involvement in requests for ICD deactivation and 77.6% reported involvement in pacemaker deactivation (P < 0.001). Having cared for a terminally ill patient for whom the respondent or a physician had ordered device deactivation was common (95.4% for ICDs vs 84.8% for pacemakers; P < 0.001). Having personally deactivated a device was also common (92.4% for ICDs vs 76.6% for pacemakers; P < 0.001). More respondents said they were comfortable with personally deactivating an ICD than deactivating a pacemaker (56.7% for ICDs vs 34.4% for pacemakers; P < 0.001). Respondents reported that the industry representative is the individual who deactivates the device most of the time (59.3% for ICDs and 49.7% for pacemakers).

Conclusions:Deactivation of implanted cardiac devices in terminally ill patients is common. Practices and attitudes associated with pacemaker deactivation differ significantly from those associated with ICD deactivation. Professional groups should develop guidelines for managing requests for implanted cardiac device deactivation and should clarify the role of device industry representatives in these deactivations.
Stimulation Rate and the Optimal Interventricular Interval during Cardiac Resynchronization Therapy in Patients with Chronic Atrial Fibrillation
Authors: VAN GELDER BERRY M. , MEIJER ALBERT , BRACKE FRANK A.
Published: April 2008

Background: Optimization of cardiac resynchronization therapy (CRT) with respect to the interventricular (V‐V) interval is mainly limited to pacing at a resting heart rate. We studied the effect of higher stimulation rates with univentricular and biventricular (BiV) pacing modes including the effect of the V‐V interval optimization.

Methods: In 36 patients with heart failure and chronic atrial fibrillation (AF), the effects of right ventricular (RV), left ventricular (LV), simultaneous BiV, and optimized sequential BiV (BiVopt) pacing were measured. The effect of the pacing mode and the optimal V‐V interval was determined at stimulation rates of 70, 90, and 110 ppm using invasive measurement of the maximum rate of left ventricular pressure rise (LV dP/dtmax).

Results: The average LV dP/dt max for all pacing modalities at stimulation rates of 70, 90, and 110 ppm was 781 ± 176, 833 ± 197, and 884 ± 223 mmHg/s for RV pacing; 893 ± 178, 942 ± 186, and 981 ± 194 mmHg/s for LV pacing; 904 ± 179, 973 ± 187, and 1052 ± 206 mmHg/s for simultaneous BiV pacing; and 941 ± 186, 1010 ± 198, and 1081 ± 206 mmHg/s for BiVopt pacing, respectively. In BiVopt pacing, the corresponding optimal V‐V interval decreased from 34 ± 29, 28 ± 28, and
21 ± 27
ms at stimulation rates of 70, 90, and 110 ppm, respectively
. In two individuals, LV dP/dtmax decreased when the pacing rate was increased from 90 to 110 ppm.

Conclusion: In patients with AF and heart failure, LV dP/dtmax increases for all pacing modalities at increasing stimulation rates in most, but not all, patients. The rise in LV dP/dtmax with increasing stimulation rates is higher in biventricular (BiV and BiVopt) than in univentricular (LV and RV) pacing. The optimal V‐V interval at sequential biventricular pacing decreases with increasing stimulation rates.
Elevated Serum Creatinine at Baseline Predicts Poor Outcome in Patients Receiving Cardiac Resynchronization Therapy
Authors: SHALABY ALAA , El‐SAED AIMAN , VOIGT ANDREW , ALBANY CONSTANTINE , SABA SAMIR
Published: April 2008

Background: Renal insufficiency is recognized as a predictor of mortality and poor outcome in heart failure patients. We sought to study the impact of baseline serum creatinine on subsequent outcome in cardiac resynchronization therapy (CRT) recipients.

Methods: We retrospectively reviewed hospital records of all CRT recipients at Pittsburgh Veterans Affairs (VA) Healthcare System (2003–2005) and University of Pittsburgh Medical Center (2004)
. We recorded clinical characteristics at the time of implantation including demographics, New York Heart Association (NYHA) functional class, ejection fraction, QRS duration, cardiomyopathy etiology, medical history, medication use, and serum creatinine. Mortality alone and mortality combined with heart failure hospitalization were the study endpoints.

Results: Out of the 330 patients studied, a total of 66 (20.0%) patients died over a mean follow‐up duration of 19.7 ± 9.0 months (range 1–44). The cohort was studied by three creatinine tertiles (0.6–1.0, 1.1–1.3, 1.4–3.0 mg/dL). Both study endpoints were observed more frequently in patients in the highest creatinine tertile compared to others (28.7% vs 14.0%, P = 0.008 for death and 41.6% vs 21.5%, P = 0.001 for the combined endpoint). High creatinine remained an independent predictor of mortality (hazard ratio [HR] 1.89, 95% confidence interval [CI] 1.06–3.39, P = 0.032) and the combined endpoint (HR 1.94, 95% CI 1.20–3.13, P = 0.007) in multivariate adjusted models. Studied as a continuous variable, increase in creatinine level by 0.1 mg/dL was associated with an 11% increase in mortality risk and a 7% increase in the combined endpoint.

Conclusion: In an unselected cohort of CRT recipients, the baseline creatinine was found to predict worse survival and poor outcome over a modest follow‐up duration.
The Role of Tilt Training in Preventing Recurrent Syncope in Patients with Vasovagal Syncope: A Prospective and Randomized Study
Authors: DUYGU HAMZA , ZOGHI MEHDI , TURK UGUR , AKYUZ SERDAR , OZERKAN FILIZ , AKILLI AZEM , ERTURK UMIT , ONDER REMZI , AKIN MUSTAFA
Published: April 2008

Background: Recurrent vasovagal syncope (VVS) can be a severely disabling disorder that may lead to an important deterioration of quality of life because of the severity and recurrence of episodes. This study sought to investigate the effectiveness of repeated orthostatic self‐training in preventing syncope in patients with recurrent VVS.

Methods: Eighty‐two consecutive patients (mean age 41 ± 4 years, 37 males) with recurrent VVS episodes and positive head‐up tilt testing (HUT) were enrolled in this study. The patients were then randomized (1:1) to conventional therapy or conventional therapy plus additional tilt training sessions. The patients were followed for spontaneous syncope for one year. Primary end‐points were the recurrence of syncope, the number of episodes, and the interval of time to the first recurrence.

Results: There were no significant differences of baseline clinical characteristics and parameters of HUT between the tilt training and control groups. The patients had 4 ± 2/year syncopal episodes prior to the HUT. The mean follow‐up after randomization was 12 ± 2 months. Spontaneous syncope recurrence during follow‐up was 56% (23 patients) versus 37% (15 patients) in the control and tilt training groups, respectively (P = 0.1). Time to first recurrence was also similar in both groups (70 ± 20 days vs 50 ± 15 days, P = 0.09). The frequency of recurrent syncopes was similar in all types of VVSs while the rate of episodes was significantly higher in control group in patients with vasodepressor type during follow‐up period (32% vs 10%, P = 0.04). The mean number of recurrent syncope episodes was also similar in both groups (3 ± 1 vs 2 ± 1, P = 0.4).

Conclusions: Tilt training was unable to influence the spontaneous syncope recurrence for recurrent VVS except for vasodepressor type.
Complete Heart Block Following Penetrating Chest Trauma in Operation Iraqi Freedom
Authors: ECKART ROBERT E. , FALTA EDWARD M. , STEWART ROBERT W.
Published: April 2008

We present a 30‐year‐old US army soldier who had penetrating chest trauma from a road side explosive with focal cardiac injury. The soldier had penetration of his right atrium and subsequent traumatic membranous ventricular septal defect and complete heart block. He was brought to a Combat Support Hospital where fortuitously the assigned trauma surgeon on‐call was a cardiothoracic surgeon, and the assigned trauma intensivist on‐call was a cardiac electrophysiologist. Of course, the only source they knew of a pacemaker was halfway around the world. We discuss the management of this injury in an austere combat environment.
Ocular manifestations in liver transplant recipients with familial amyloid polyneuropathy
Authors: Sandgren Ola , Kjellgren Daniel , Suhr Ole B.
Published: April 2008

Purpose:  To evaluate postoperative ocular involvement in Swedish liver transplant (LT) recipients with familial amyloid polyneuropathy (FAP).

Methods:  Routine ophthalmological examinations were performed in 48 LT recipients, with particular attention given to amyloid deposition in the anterior segment and the vitreous body. Medical records were scrutinized for information regarding neurological impairment at the time of the LT. The diagnosis was secured in all cases by examining for amyloid deposits in biopsy specimens and positive genetic testing for amyloidogenic transthyretin (ATTR) Val30Met mutation.

Results:  Six patients (12.5%) developed vitreous opacities within the post‐LT observation period. The first opacities were seen 40 months after transplantation, 8 years after the onset of systemic disease. Four patients (8%) developed secondary glaucoma, the first of which was observed 18 months after the procedure and 6.5 years after the onset of disease. Sixteen patients (33%) developed deposits on the anterior surface of the lens. Scalloped pupillary margins were noted in 10 patients (21%).

Conclusion:  The prevalence of eye complications increases with time after LT and regular follow‐up is necessary, especially to disclose the development of glaucoma – a complication with insidious symptoms of which patients are normally unaware.
Use of mental health services and complementary and alternative medicine in persons with common mental disorders
Authors: Wahlström M. , Sihvo S. , Haukkala A. , Kiviruusu O. , Pirkola S. , Isometsä E.
Published: April 2008

Objective:  Few studies investigated the use of complementary and alternative medicine (CAM) by subjects with mental disorders. We examined the relationship between depressive, anxiety and alcohol‐use disorders and their comorbidity, as well as the relationship between use of CAM and use of mental health services.

Method:  The Finnish adult (≥30 years) population‐based Health 2000 Study (n = 5987) collected information on use of CAM plus health and mental health care services.

Results:  Generalised anxiety disorder and panic disorder were positively associated and alcohol abuse was negatively associated with use of CAM. The prevalence was highest in persons with comorbidity of anxiety and depressive disorders. The use or perceived usefulness of mental health services did not differ between CAM users and other participants.

Conclusion:  The relationship between the use of CAM and mental disorders appears to vary depending on the type of mental disorder. Use of CAM seems unrelated to the use and the perceived usefulness of mental health services.
Abnormal medial prefrontal cortex connectivity and defective fear extinction in the presymptomatic G93A SOD1 mouse model of ALS
Authors: Sgobio C. , Trabalza A. , Spalloni A. , Zona C. , Carunchio I. , Longone P. , Ammassari‐Teule M.
Published: April 2008

Amyotrophic lateral sclerosis (ALS) is a fatal progressive neuropathy associated with the degeneration of spinal and brainstem motor neurons. Although ALS is essentially considered as a lower motor neuron disease, prefrontal cortex atrophy underlying executive function deficits have been extensively reported in ALS patients. Here, we examine whether prefrontal cortex neuronal abnormalities and related cognitive impairments are present in presymptomatic G93A Cu/Zn superoxide dismutase mice, a mouse model for familial ALS. Structural characteristics of prelimbic/infralimbic (PL/IL) medial prefrontal cortex (mPFC) neurons were studied in 3‐month‐old G93A and wild‐type mice with the Golgi–Cox method, while mPFC‐related cognitive operations were assessed using the conditioned fear extinction paradigm. Sholl analysis performed on the dendritic material showed a reduction in dendrite length and branch nodes on basal dendrites of PL/IL neurons in G93A mice. Spine density was also decreased on basal dendrite segments of branch order five. Consistent with the altered morphology of PL/IL cortical regions, G93A mice showed impaired extinction of conditioned fear. Our findings indicate that abnormal prefrontal cortex connectivity and function are appreciable before the onset of motor disturbances in this model.
Effects of early experience and genotype on serotonin transporter regulation in infant rhesus macaques
Authors: Kinnally E. L. , Lyons L. A. , Abel K. , Mendoza S. , Capitanio J. P.
Published: April 2008

The moderating effect of early experience on gene‐behavior associations has been well characterized. The molecular events that allow for such moderation are not well understood, however. We assessed the impact of early experience and serotonin transporter linked promoter polymorphism (rh5‐HTTLPR) genotype on peripheral serotonin transporter (5‐HTT) regulation in response to a maternal/social separation and relocation stressor in infant rhesus macaques. We further tested the hypothesis that modulation of 5‐HTT regulation by rearing and/or genotype is mediated by glucocorticoid (GC) availability. Fifty‐three infant (3–4 months of age) rhesus macaques that were either nursery reared (NR) or mother reared (MR) were genotyped for rh5‐HTTLPR. Infants were blood sampled within 2.5 h of maternal or social separation/relocation and again 5 h later. Infants were then administered dexamethasone, a synthetic GC and blood sampled 16.5 h later. 5‐HTT RNA was quantified from peripheral blood mononuclear cells. Plasma cortisol was measured at all time points. The MR individuals upregulated 5‐HTT significantly during maternal/social separation, while NR individuals did not. Concomitant increases in cortisol were not observed, but dexamethasone treatment stimulated 5‐HTT expression regardless of genotype/rearing group, and 5‐HTT expression in the post‐stressor sample was correlated with plasma cortisol levels at all time points. Our data indicate that early experience exerted a strong influence on 5‐HTT regulation during a stressor in infant rhesus macaques independent of rh5‐HTTLPR genotype. We also showed that GCs may stimulate 5‐HTT expression but that there likely exist faster‐acting transcriptional regulators of 5‐HTT that are in place as a function of experience.
Alternative binding proteins: Anticalins – harnessing the structural plasticity of the lipocalin ligand pocket to engineer novel binding activities
Authors: Skerra Arne
Published: April 2008

Antibodies are the paradigm for binding proteins, with their hypervariable loop region supported by a structurally rigid framework, thus providing the vast repertoire of antigen‐binding sites in the immune system. Lipocalins are another family of proteins that exhibit a binding site with high structural plasticity, which is composed of four peptide loops mounted on a stable β‐barrel scaffold. Using site‐directed random mutagenesis and selection via phage display against prescribed molecular targets, it is possible to generate artificial lipocalins with novel ligand specificities, so‐called anticalins. Anticalins have been successfully selected both against small hapten‐like compounds and against large protein antigens and they usually possess high target affinity and specificity. Their structural analysis has yielded interesting insights into the phenomenon of molecular recognition. Compared with antibodies, they are much smaller, have a simpler molecular architecture (comprising just one polypeptide chain) and they do not require post‐translational modification. In addition, anticalins exhibit robust biophysical properties and can easily be produced in microbial expression systems. As their structure–function relationships are well understood, rational engineering of additional features such as site‐directed pegylation or fusion with functional effector domains, dimerization modules or even with another anticalin, can be readily achieved. Thus, anticalins offer many applications, not only as reagents for biochemical research but also as a new class of potential drugs for medical therapy.
Prevalence of Sexual Dysfunction in Female Outpatients and Personnel at a Colombian Hospital: Correlation with Hormonal Profile
Authors: Garcia Sandra , Moreno Socorro , Aponte Hernan
Published: April 2008

Introduction

Female sexual dysfunction (FSD) is a multifactorial entity and an underestimated problem with an overall prevalence between 20% and 50%. Prevalence can change according to the diagnostic criteria used, data collection, and others such as psychological and cultural factors. Population studies of FSD are limited, both in Colombia and in other countries. Nevertheless, because of the prevalence found in other studies, FSD can be considered a public health issue that affects the quality of life of women who suffer from it and their partners.

Aim

To determine the prevalence of FSD and its correlation with the hormonal profile in female outpatients and female staff at San Jose Hospital (Bogotá, Colombia).

Methods

We performed a cross-sectional study with endocrine measurements.

Main Outcome Measures

The prevalence of FSD according to the Female Sexual Function Index (FSFI) cutoff points, and androgenic deficiency defined as women with a proportion of free testosterone below 2%. Demographic characteristics, medical history survey, FSFI, and a hormonal profile that included follicle stimulating hormore (FSH), luteinizing hormone (LH), prolactin, estrone, estradiol, sulphate and total dehydroepiandrosterone, androstenedione, sex hormone binding globulin, and total testosterone.

Results

Fifty (49.5%; 95% confidence interval [CI]: 39.4–59.6%) out of 101 participants met the criteria for FSD; in those women with sexual activity in the past 4 weeks, the prevalence of FSD was 37.8% (95% CI: 27.3–49.1%). In the hormone evaluation sample, 29 out of 32 women with sexual activity in the past 4 weeks met the criteria for FSD. Our results suggest that there is independence between the FSFI scores and the proportion of free testosterone.

Conclusions

Our findings suggest that FSD in our population has a prevalence as high as that previously reported in the literature; however, because of the sample selection criteria, we could not say that our study results may well reflect the prevalence in our general Colombian population.
Erectile Dysfunction and Men's Health: Developing a Comorbidity Risk Calculator
Authors: Shabsigh Ridwan , Shah Manan , Sand Michael
Published: April 2008

Introduction

The association between erectile dysfunction (ED) and cardiovascular risk factors is well established and ED can be considered an early marker for cardiovascular disease.

Aim

To generate a calculator to predict the risk of diabetes, hypertension, hyperlipidemia or angina in men with ED, based on an analysis of data from the Men's Attitudes to Life Events and Sexuality (MALES) 2004 study.

Main Outcome Measure

A logistic regression model using the variables overall health, ED severity, having/not having a sexual partner, and waist size.

Methods

The MALES was a multinational, population-based study conducted in 2001, in which the prevalence of ED and comorbid medical conditions was assessed in 27,839 men aged 20–75 years. In 2004, the cohort of men with ED (N = 1843) were recontacted and 919 (50%) agreed to participate in the MALES 2004 longitudinal study. Multistep analysis of data from 808 patients was performed, with 289 variables evaluated. Only those variables significantly correlated with outcome and those making clinical sense were retained. A logistic regression model was applied to 90% of the sample; results were validated in the remaining 10% with sensitivity and specificity testing.

Results

Of the 2004 cohort, 20.7% had been diagnosed with diabetes, 44.3% with hypertension, 42.5% with hyperlipidemia, and 25.7% with angina. The following modifiable factors affected the risk of comorbidities, and were therefore included in the risk calculator: health status, waist size, ED severity, and having or not having a sexual partner. Using these variables in the model resulted in a sensitivity of 86.2% and specificity of 54.5%. The primary limitation of the calculator is that it is not a prediction calculator.

Conclusion

Erectile dysfunction is a key factor in calculating the probability of major risks to men's health, such as diabetes, hypertension, hyperlipidemia, and angina.
High Cholesterol Feeding in C57/Blc6 Mice Alters Expression within The VEGF Receptor-Ligand Family in Corporal Tissue
Authors: Xie Donghua , Hazarika Surovi , Andrich Amy J. , Padgett Mike E. , Kontos Christopher D. , Donatucci Craig F. , Annex Brian H.
Published: April 2008

Introduction

Angiogenesis, the growth and proliferation of blood vessels from existing vascular structures, is mediated by many cytokine growth factors and receptors, among the most important are the vascular endothelial growth factor (VEGF) family.

Aim

Decreases in VEGF receptor signaling have been linked to abnormalities in vasoreactivity in corporal tissue, but it is unknown if alterations in the VEGF ligands and/or receptors contribute to this process.

Main Outcome Measures

We sought to determine changes in vasoreactivity and the expression of the family of VEGF ligands and receptors in corporal tissue with cholesterol feeding in C57BL6 mice.

Methods

Twenty-four mice (N = 8/group) were fed a normal diet (Group 1) or a 1.25% high cholesterol diet for 4 (Group 2) or 12 (Group 3) weeks. Isometric tension studies were performed on corporal strips and dose response curves were generated to evaluate endothelium-dependent and endothelium-independent vasoreactivities. Levels of VEGF-A, B, C, D, VEGF receptors (VEGFRs) were detected by PCR (polymerase chain reaction) and/or western blot/enzyme-linked immunosorbent assay (ELISA). Endothelial and smooth muscle cell contents were determined by immunohistochemistry.

Results

At 4 weeks there was a small but significant decrease in endothelium-dependent vasoreactivity. Both mRNA and protein levels of VEGFR-1 were decreased, while VEGF-B was increased in Group 2 vs. Group 1, with no change in VEGF-A or endothelial cell content. By 12 weeks, decreases in both endothelium-dependent and endothelium-independent vasoreactivity were evident with decrease in most VEGF ligands (except VEGF-B), receptors, and receptor signaling.

Conclusions

Cholesterol feeding in C57BL6 mice results in alterations in the VEGF receptor-ligand family that may initially serve to limit the degree of vascular injury but these adaptations fail with the continuation of cholesterol feeding.
CHANGES OF OMEGA‐3 FATTY ACID CONTENT AND LIPID COMPOSITION IN CANNED TUNA DURING 12‐MONTH STORAGE
Authors: SIRIAMORNPUN SIRITHON , YANG LIFENG , KUBOLA JITTAWAN , LI DUO
Published: April 2008

The effect of storage time on the concentration and lipid and fatty acid compositions of canned tuna in brine was studied. Lipid and fatty acid were analyzed during 0, 3, 6, 9 and 12 months of storage at room temperature. Concentrations of lipids and total saturated fatty acids were significantly increased after storage for 9 months. The concentrations of total polyunsaturated fatty acids (PUFAs), total n‐3 and n‐6 PUFA were significantly stepwise decreased with increased storage time (P < 0.05); 22:6n‐3 and 22:5n‐3 started to decrease significantly at 6 months, and 20:5n‐3 and 20:4n‐6 decreased at 3 months (P < 0.05). The n‐3/n‐6 ratio significantly decreased from 3.8 at 0 month to 3.2 at 9 months (P < 0.05). Cholesterol ester was significantly increased while the other four classes of lipids, namely, phospholipids, triacylglycerols, free fatty acids and sterols, showed an opposite trend during 12 months of storage. Lipid oxidation measured by peroxide value and thiobarbituric acid value showed gradual increases with storage time. Thus, canned tuna in brine should not be stored more than 6 months with consideration of the stability of n‐3 fatty acids.

PRACTICAL APPLICATIONS

Canned foods are significant dietary items, especially for bush walkers, travelers and armed service personnel. Canned fish, one of the important sources of long‐chain n‐3 polyunsaturated fatty acids (PUFAs), have an equivalent n‐3 PUFA content as fresh fish. Long‐chain PUFA in fresh fish is unstable and easy to oxidize. Appropriate process produced canned fish have a number of advantages such as odor, taste, shelf life, storage and carrying compared with fresh fish. We have investigated the lipid oxidation and fatty acid alteration sequentially during a 12‐month storage because there has been no such data available in the literature. The data from the present study could provide useful information for industries, consumers and public health workers.
CHLORINATED CONTAMINANTS IN EXTRA‐VIRGIN OLIVE OIL FROM CENTRAL ITALY
Authors: GUERRANTI CRISTIANA , PERRA GUIDO , RENZI MONIA , FOCARDI SILVIA , FOCARDI SILVANO
Published: April 2008

Synthetic chemical compounds, such as organochlorines, are known for their persistence and toxicity. The diet represents, for the general population, the main route of exposure to these contaminants, because organochlorines in food constitute a significant health risk, and olive oil has a high consumption rate among people of the producing countries; the control of residues in olive oil is of great importance. In this study, the presence of residues of hexachlorobenzene (HCB), dichlorodiphenyltrichloroethane (DDT) and polychlorinated biphenyls (PCBs) was assessed in samples of extra‐virgin olive oil from Tuscany (central Italy). The analyses revealed the presence of HCB in concentrations below the detection limit; DDT and PCBs were instead present in all samples tested, and PCB concentrations were always higher than those of DDT, from 1.24 to 29.35, and from 0.01 to 1.83 ng/g wet weight, respectively.

PRACTICAL APPLICATIONS

Because organochlorines in food constitute a significant health risk, and olive oil has a high consumption rate among people of the producing countries, the control of residues in olive oil is of great importance. For the first time here, we present data on organochlorine pollution in oil samples collected in Tuscany, and assess the intake ranges of pollutants related to consumption of the oils analyzed. Showing the low contamination levels of Tuscan olive oil, we wish to confirm the high quality of this kind of food lipid.
PHOSPHATIDYLCHOLINE LEVELS AND THEIR FATTY ACID COMPOSITIONS IN SQUID EGG: A COMPARISON STUDY WITH POLLACK ROE AND STURGEON CAVIAR
Authors: WANG QI , XUE CHANG‐HU , LI ZHAO‐JIE , XU JIE
Published: April 2008

The content of total lipids (TLs), composition of phospholipids (PLs) and main fatty acids of phosphatidylcholine (PC) were determined in egg of squid Sthenoteuthis oualaniensis, roe of Alaska pollack Theragra chatcogramma and caviar of sturgeon Acipenser gueldenstaedti. The PL content of squid egg (72.0 ± 3.2% of TL) was higher than the other two kinds of fish eggs. A high‐performance liquid chromatography/evaporate light‐scattering detector method was used for qualitative and quantitative analyses of the PLs. The PC content of squid egg (67.50 ± 0.55% of PL) was the highest. Docosahexaenoic acid (22:6n‐3, DHA) percentage of PC in squid egg (40.0 ± 0.4 mol %) was much higher than others. The results indicated that squid egg could be used as a new source of PC rich in DHA.

PRACTICAL APPLICATIONS

This study compares the phospholipids in egg from the squid Sthenoteuthis oualaniensis with two kinds of known fish eggs. The squid source was abundant in phospholipids, but it is not fully utilized because of the low‐edible value of the meat. The analysis of the phospholipid classes was carried out by using a high‐performance liquid chromatography/evaporative light‐scattering detector. The method has been used in the dairy industry, but is not so common in fish product evaluation. Our results showed that it is quick and sensitive in detecting the fish and shellfish egg phospholipids. Squid egg contained a large amount of phosphatidylcholine and was rich in docosahexaenoic acid, thus may serve as a novel functional lipid for health promotion. Therefore, squid egg may serve as a valuable good source of functional lipids.
Structures of the Chromophore Binding Sites in BLUF Domains as Studied by Molecular Dynamics and Quantum Chemical Calculations†
Authors: Obanayama Kazuya , Kobayashi Hiroaki , Fukushima Kentaro , Sakurai Minoru
Published: April 2008

BLUF (blue‐light sensing using FAD) domains constitute a new family of flavin‐based blue light photoreceptors. The photocycle of BLUF is unique in the sense that a few hydrogen bond rearrangements are accompanied by only slight structural changes in the bound chromophore. The hydrogen bond rearrangements upon illumination have been inferred from spectral changes in the chromophore: ∼10 nm redshift of the absorption maximum and ∼16 cm−1 downshift of the C4=O stretching frequency. However, the exact features of the hydrogen bond network around the active site are still the subject of some controversy. In particular, the orientation of a conserved Gln (Gln63 in AppA) is presently one of the most questioned topics in the field. Here we perform molecular dynamics simulations for the wild‐type AppA, AppA1‐124C20S, BlrB and T110078 and furthermore quantum chemical calculations to investigate their spectroscopic properties in the dark and signaling states. On the basis of these results, we reveal the dynamic aspect of hydrogen bonding networks at the active site and propose theoretically reasonable models for the dark and signaling states of the BLUF domains.
Evaluating Cover Crops (Sudex, Sunn Hemp, Oats) for Use as Vegetative Filters to Control Sediment and Nutrient Loading From Agricultural Runoff in a Hawaiian Watershed1
Authors: Ryder M.H. , Fares A.
Published: April 2008

Abstract:  A study was conducted to determine the effects of three land covers (sunn hemp –Crotalaria juncea, sudex, a sorghum‐sudangrass hybrid –Sorghum bicolor x S. bicolor var. sudanese, and common oats –Avena sativa) planted as vegetative filter strips on the reduction of sediment and nutrient loading of surface runoff within the Kaika‐Waialua watershed on the island of Oahu, Hawaii. Runoff samples were collected and analyzed for total suspended solids (TSS), total dissolved solids (TDS), phosphorous, and three forms of nitrogen (nitrate, ammonium, total nitrogen). Study results show that during seven out of 10 runoff events, the three cover crop treatments significantly reduced TSS as compared to the fallow treatment. Average removal efficiencies were 85, 77, and 73% for oats, sunn hemp, and sudex, respectively, as compared to the fallow treatment. Nutrient concentrations were low with phosphorous concentrations, lower than 1 (μg/ml) for all treatments, and total nitrogen (TN) concentrations below 7 (μg/ml) except in the sunn hemp treatment, where TN concentrations were less than 10 (μg/ml). Results of analysis of TDS showed that the cover crop treatments did not decrease dissolved solids concentrations in comparison with the fallow treatment. Analysis of nutrient concentrations in runoff samples did not detect any significant decreases in phosphorous, nitrogen, ammonium, or TN concentrations in comparison to the fallow treatment. However, a significant increase in TN concentrations in the sunn hemp treatment was detected and showed the nitrogen fixing capacity of sunn hemp. No treatment effects on runoff volume were detected, and runoff volumes were directly correlated with rainfall amounts showing no crops significantly impacted soil infiltration rates. These results were attributed to extremely low soil hydraulic conductivities (0.0001‐7 cm/day at the soil surface, 15 and 30 cm below the soil surface). This study showed that cover crops planted as vegetative filters can effectively reduce sediment loads coming from idle and fallow fields on moderately steep volcanically derived highly weathered soils.
A Stochastic Modeling Approach to Address Hydrogeologic Uncertainties in Modeling Wellhead Protection Boundaries in Karst Aquifers1
Authors: Guha Hillol
Published: April 2008

Abstract:  Development of any numerical ground‐water model is dependent on hydrogeologic data describing the subsurface. These data are obtained from geologic core analyses, stratigraphic analyses, aquifer performance tests, and geophysical studies. But typically in remote areas, these types of data are very sparse and site‐specific in terms of the aerial extent of the resource to be modeled. Uncertainties exist as to how well the available data from a few locations defines a heterogeneous surficial aquifer such as the Biscayne Aquifer in Miami‐Dade County, Florida. This is particularly the case when an exceptionally conductive horizontal flow zone is detected at one site due to specialized testing that was not historically conducted at the other at sites that provided data for the model. Not adequately accounting for the potential effect of the high flow zone in the aquifer within a ground‐water numerical model, even though the zone may be of very limited thickness, might underpredict the well field protection capture boundaries. Applied Stochastic ground‐water modeling in determining well field protection zones is steadily becoming important in addressing the uncertainty of the hydrogeologic subsurface parameters, specifically in karstic heterogeneous aquifers. This is particularly important in addressing the uncertainty of a 60‐day travel time capture zone in the Northwest Well Field, Miami‐Dade County, where a predominantly high flow zone controls much of the flow in the production wells. A stochastic ground‐water modeling application along with combination of pilot points and regularization technique is presented to further consolidate the uncertainty of the subsurface.
Effective Efficiency as a Tool for Sustainable Water Resources Management1
Authors: Haie Naim , Keller Andrew A.
Published: April 2008

Abstract:  The sufficiency and usefulness of Effective Efficiency (EE) as a water resources index is shown through conceptual formulation of a generalized EE and practical applications. Two EE models are proposed: one is based on water quantity and the other on quantity and quality, with the possibility of considering water reuse (recycling) in both. These models were developed for two scales: the first is called Project EE and the second Basin EE. The latter gives the influence of the project on the water resources systems of the basin while the former does not make such connection to the whole basin. Such considerations give proper signals as to the adequacy of any intervention to increase efficiency. A crucial distinction is made between depletion and diversion water savings. Classical Efficiency (CE) models are analyzed and compared with the various EE models. CE results in values that are less than EE because of not considering water reuse and water quality in its calculation. Some authors, pointing to these problems – particularly the first problem – have advocated the use of hydrological “fractions” instead of efficiency concepts. This paper defends the use of a proper efficiency model such as EE and suggests putting an end to the use of the CE indicators. To test the models, they are applied to five cases of irrigation and city water use in the United States and Egypt. The analysis of the results demonstrates all the points mentioned above and the potential of the EE models to adequately describe the water resources efficiency and sustainability at a location.