bluuebunny/crossref_metadata_2025 huggingface dataset:
Annual variation in source contributions to a mixed stock: implications for quantifying connectivity
Authors: BJORNDAL KAREN A. , BOLTEN ALAN B.
Published: March 2008

Connectivity among populations of highly migratory species is an area of active research and is often quantified with genetic markers. We determined mitochondrial DNA (mtDNA) sequences in 350 green turtles, Chelonia mydas, in 10 annual samples over a 12‐year period from an aggregation of immature green turtles in the southern Bahamas. We found significant temporal structuring in haplotype frequencies among years for all turtles and for recruits. These significant differences were reflected in substantial variation in the relative contributions from different rookeries among years estimated by a Bayesian hierarchical model. Because this foraging aggregation has been the subject of a demographic study for over 30 years, we were able to determine that, among the three potential causes of temporal structuring—differential recruitment, mortality and emigration—recruitment accounts for most of this variation. We found that estimates of connectivity and genetic diversity in sea turtle populations are affected by the level of temporal variation reported here. More studies on the extent of temporal variation in composition of mixed stocks of other migratory species are needed to determine how this affects measures of connectivity.
The SUI‐homologous translation initiation factor eIF‐1 is involved in regulation of ion homeostasis in rice
Authors: Diédhiou C. J. , Popova O. V. , Dietz K.‐J. , Golldack D.
Published: March 2008

Halophytes survive high salinity by using complex adaptive mechanisms. In a search for novel molecular mechanisms involved in salt acclimation, transcript analyses revealed increased expression of a SUI‐homologous translation initiation factor eIF‐1 in the salt‐tolerant grass species Festuca rubra ssp. littoralis but not in rice. Upon analysis of the cell specificity of eIF‐1 transcription by in situ polymerase chain reaction (PCR), predominant signals were detected in rice leaf mesophyll. To further examine the role of eIF‐1 in salt tolerance, transgenic rice plants were generated that over‐express this factor under the control of the CaMV‐35S promoter. The eIF‐1 over‐expressing lines showed improved growth under salt stress that was correlated with maintenance of photosynthetic activity and reduced Na+ and Cl− accumulation in leaves. The transgenic rice lines also activated expression of the vacuolar H+‐ATPase. In addition, an oxidoreductase that belongs to the aldo/keto reductase family was identified as a gene with modified expression in the eIF‐1 over‐expressing lines, compared with wild‐type rice. Our data suggest that eIF‐1 has a central function in salt‐stress adaptation in rice by regulating ion accumulation and the intracellular redox status.
Transcriptional differences between the male‐sterile mutant bcms and wild‐type Brassica campestris ssp. chinensis reveal genes related to pollen development
Authors: Huang L. , Cao J. , Ye W. , Liu T. , Jiang L. , Ye Y.
Published: March 2008

A novel male‐sterile mutant which lacks mature pollen, Brassisa campestris male sterile (bcms), was identified in Brassica campestris L. ssp. chinensis Makino (syn. B. rapa ssp. chinensis). Genetic analysis revealed that bcms was controlled by a single recessive mutation locus. Genome‐wide transcriptional profiling was performed on the flower buds of both the bcms mutant and the wild‐type from which it originated, and profiling analysis indicated that there were numerous changes in gene expression attributable to the gene mutation. This mutation resulted in down‐regulation of a variety of genes and up‐regulated expression of a few other genes. A total of 51 transcript‐derived fragments (TDFs) were isolated: 32 specifically and 12 predominantly accumulated in wild‐type flower buds, and two specifically and five predominantly accumulated in bcms flower buds. Sequence analysis showed that some of these TDFs share significant similarities with genes involved in different aspects of cellular development, such as signal transduction, cell wall biosynthesis and regulation. Most other TDFs showed no or very poor sequence similarities to entries in any database and might represent new candidate proteins involved in pollen development. Furthermore, spatial and temporal expression pattern analysis of 20 genes derived from cDNA‐amplified fragment length polymorphism in different tissues of both the bcms and wild‐type plants revealed their complex and dynamic expression patterns. The bcms mutant and the genes isolated in this paper provide excellent material for future studies on the molecular mechanism of male sterility.
Activation of phasic pontine‐wave generator in the rat: a mechanism for expression of plasticity‐related genes and proteins in the dorsal hippocampus and amygdala
Authors: Datta Subimal , Li Guangmu , Auerbach Sanford
Published: March 2008

A number of behavioral studies have emphasized the importance of interactions between the pontine‐wave (P‐wave) generator and the dorsal hippocampus (DH) in two‐way active avoidance (TWAA) memory processing; however, the direct involvement of the P‐wave generator in the TWAA training trial‐induced molecular events in the DH and amygdala has not been systematically evaluated. Here we demonstrate that the TWAA learning training trials activate P‐wave generator, and increase phosphorylation of CREB (pCREB) and expression of activity‐regulated cytoskeletal‐associated (Arc) protein, as well as messenger ribonucleic acid (mRNAs) of Arc, brain‐derived nerve growth factor (BDNF) and early growth response‐1 (Egr‐1) in the DH and amygdala. Selective elimination of P‐wave‐generating cells abolished P‐wave activity and suppressed TWAA learning training trial‐induced expression of pCREB and Arc proteins and Arc, BDNF and Egr‐1 mRNAs in the DH and amygdala. Following a session of TWAA training, all rats were equal in terms of time spent in wakefulness, slow‐wave sleep and rapid eye movement (REM) sleep irrespective of P‐wave lesions. The second set of experiments demonstrated that localized cholinergic stimulation of the P‐wave generator increased expression of Arc, BDNF and Egr‐1 mRNAs in the DH. Together, these findings provide the first direct evidence that activation of P‐wave‐generating cells is critically involved in the TWAA training trial‐induced expression of plasticity‐related genes in the DH and amygdala. These findings are discussed in relation to the role of P‐wave generator activation for the REM sleep‐dependent development and cognitive functions of the brain.
Role of odour compounds in the attraction of gamete vectors in endophytic Epichloë fungi
Authors: Steinebrunner Fabrizio , Twele Robert , Francke Wittko , Leuchtmann Adrian , Schiestl Florian P.
Published: March 2008

DOI: 10.1111/j.1469-8137.2008.02428.x
Global cognitive function in children with epilepsy: A community‐based study
Authors: Berg Anne T. , Langfitt John T. , Testa Francine M. , Levy Susan R. , DiMario Francis , Westerveld Michael , Kulas Joseph
Published: March 2008

Summary

Purpose: To determine the frequency and determinants of subnormal global cognitive function in a representative, community‐based sample of children prospectively identified at the time of initial diagnosis of epilepsy.

Methods: In children enrolled with newly diagnosed epilepsy and followed a median of 10.5 years, level of cognitive function (within normal, borderline, mild, moderate to severe mental retardation (MR), neurologically devastated, and impaired but not further classified (NFC)) was determined based upon neurologists' and school records, repeated parental interviews, and, in over half the participants, standardized neuropsychological testing. For multivariable analyses, subnormal cognitive function was designated as consistent with a full scale IQ < 80.

Results: Global cognitive function was considered within normal, N = 451 (73.6%), borderline, N = 31 (5.1%), mild MR, N = 21 (3.4%), more severe MR, N = 45 (7.3%), devastated, N = 29 (4.7%), and impaired‐NFC, N = 36 (5.9%). Age at onset <5 years, symptomatic etiology, epileptic encephalopathy, remission status and current AED treatment were each strongly associated with level of cognitive function (all p‐values <0.0001). In a multivariable logistic regression model, all variables except remission status independently contributed to subnormal global cognitive function.

Discussion: Evidence of subnormal global cognitive function is apparent in approximately one of four children with epilepsy. Young age at onset, symptomatic cause, epileptic encephalopathy, and continued treatment, despite their strong intercorrelations, are independently associated with this outcome.
Feasibility of epilepsy follow‐up care through telemedicine: A pilot study on the patient's perspective
Authors: Ahmed Syed Nizamuddin , Mann Carly , Sinclair D. Barry , Heino Angela , Iskiw Blayne , Quigley Daphne , Ohinmaa Arto
Published: March 2008

Summary

Purpose: Cost analysis and patient satisfaction with telemedicine in epilepsy care.

Methods: This controlled study included out‐of‐town epilepsy patients coming to follow‐up at the University of Alberta hospital epilepsy clinic. After an informed consent, patients were randomized to either conventional (n = 18) or telemedicine (n = 23) clinics. Patients or caregivers filled patient satisfaction and travel cost questionnaires in both alternatives. Cost per visit analysis included costs of traveling, lodging, and lost productivity.

Results: Average age of the population was 41 years (range 19–73; 45% women). Eighty‐three percent of patients preferred their next visit through telemedicine. About 90% of patients indicated a need for companion travel (mainly by car) to conventional clinic. For the conventional group patients the value of lost productivity was CAD $201, hotel cost CAD $8.50, and the value of car mileage CAD $256.50, totaling about CAD $466.00. Patient costs for telemedicine were CAD $35.85. Telemedicine production costs are similar to the patients' savings in traveling and lost productivity. About 90% of patients in both groups were satisfied with the quality of the service.

Conclusion: Telemedicine can play a role in follow‐up care of epilepsy patients, reduce patient costs, and improve patient satisfaction. This is the first full‐time epilepsy telemedicine clinic in Western Canada.
Health resource use in epilepsy: Significant disparities by age, gender, and aboriginal status
Authors: Jetté Nathalie , Quan Hude , Faris Peter , Dean Stafford , Li Bing , Fong Andrew , Wiebe Samuel
Published: March 2008

Summary

Purpose: Epilepsy imposes a significant burden on society. The objective of this study was to estimate health resource utilization (HRU) over a 1‐year period in epilepsy patients, using administrative databases.

Methods: Three administrative databases (inpatient, emergency, and physician claims) were used to identify epilepsy cases. HRU variables included general physician (GP) and emergency (ER) visits, physician billings, hospitalizations, and length of stay (LOS). Logistic regression was used to determine the association between demographic variables and HRU variations.

Results: Among the 1,431 patients with a mean age of 37.5 ± 17.3 years, 56 (4%) were aboriginal. Ninety‐six percent of patients saw a GP or a specialist (outpatient visit), 12% were hospitalized, and 8% visited the ER. Younger patients were more likely to see a neurologist (OR = 1.7, 95% CI 1.3–2.3), visit the ER (OR = 4.9, 95% CI 3.2–7.4), or be hospitalized (OR = 2.9, 95% CI 2.0–4.3). Females were less likely to see a GP but more likely to see a neurologist. Aboriginals were more likely than nonaboriginals to visit the ER (OR = 2.3, 95% CI 1.1–5.0) or be hospitalized (OR = 2.8, 95% CI 1.5–5.1) but less likely to see a neurologist (OR = 0.3, 95% CI 0.2–0.6). Welfare status and residence location (urban vs. rural) were not associated with HRU level.

Discussion: We demonstrated the feasibility of using administrative databases to assess HRU in epilepsy. We also uncovered disparities in HRU by age, gender, and by aboriginal status, suggesting possible internal or external barriers to specialized care in some groups.
Surgical outcome of patients with mesial temporal lobe epilepsy related to hippocampal sclerosis
Authors: Özkara Çiğdem , Uzan Mustafa , Benbir Gülçin , Yeni Naz , Oz Büge , Hanoğlu Lütfü , Karaağac Naci , Özyurt Emin
Published: March 2008

Summary

Seizure outcome in mesial temporal lobe epilepsy related to hippocampal sclerosis (MTLE‐HS) that was evaluated according to a noninvasive protocol was assessed in 165 patients and reported using both Engel's and ILAE classifications. The mean postoperative follow‐up was 5.0 ± 2.7 years. At the end of first year, 77.1% of patients were in Engel‐I, and 52.7% were in ILAE‐I. Antiepileptic drugs (AEDs) were discontinued in 41 patients (42.7%), all remained seizure‐free for >2 years that could be accepted as “cure.” Thirty‐six patients had recurrences, 19 had running‐down phenomena. Anterior temporal lobectomy (ATL) was performed in 27 patients with a better outcome when compared to patients operated by selective anterior hippocampectomy. Clinical risk factors for better and worse outcome, which show some similarity in different reports, seem to veil the main reason, which is the accurate delineation of epileptogenic zone considering the presence of different subgroups and underlying developmental pathologies.
The influence of simulated shipping conditions (24‐ or 30‐hr interruption of agitation) on the in vitro properties of apheresis platelets during 7‐day storage
Authors: Wagner Stephen J. , Vassallo Ralph , Skripchenko Andrey , Einarson Mindy , Seetharaman Shalini , Moroff Gary
Published: March 2008

BACKGROUND: Platelet (PLT) components undergo interruption of agitation during shipment. Studies have demonstrated maintenance of PLT quality of whole blood–derived PLT concentrates during a 24‐hour interruption of agitation, but data are not available for apheresis PLTs in 100 percent plasma.

STUDY DESIGN AND METHODS: Apheresis PLTs were collected with one of two commercially available separators (Amicus, Fenwal, Inc.; or Trima Accel, Gambro BCT) to provide two identical PLT products, each with approximately 3 × 1011 to 4.5 × 1011 PLTs. The control product was continuously agitated. The test product was subjected to a continuous 24‐ or 30‐hour period of interrupted agitation between Day 2 and Day 3 of storage by placement in a standard shipping box at room temperature.

RESULTS: Interrupting agitation for 24 or 30 hours influenced in vitro PLT properties to various degrees. After 5 days of storage, pH levels were judged to be well maintained after 24 hours without agitation for PLTs collected with both separators (pH < 6.2, Trima [0/12] and Amicus [0/12]). The changes in other variables associated with the retention of postinfusion viability were also considered limited and acceptable in units subjected to a 24‐hour interruption of agitation. After 7 days of storage including a 24‐hour interruption of agitation, Trima PLTs better maintained PLT properties compared to Amicus PLTs. With a 30‐hour period, both Trima and Amicus PLTs were deemed satisfactory for pH at 5 days, but not at 7 days (pH < 6.2: Day 5, Trima [0/23] and Amicus [1/22]; Day 7, Trima [5/23] and Amicus [4/17]).

CONCLUSION: Based on the retention of pH levels of at least 6.2, apheresis PLT quality was maintained for 5 days with a 24‐hour and a 30‐hour interruption of agitation.
Implications of Obstructive Sleep Apnea for Atrial Fibrillation and Sudden Cardiac Death
Authors: GAMI APOOR S. , SOMERS VIREND K.
Published: March 2008

Obstructive sleep apnea (OSA) is a sleep‐related breathing disorder with important cardiovascular consequences, including arrhythmogenesis. The unique pathophysiology of OSA results in multiple intermediate mechanisms that may promote atrial fibrillation, ventricular arrhythmias, and sudden cardiac death. These mechanisms may act acutely to trigger nocturnal dysrhythmias, or chronically by affecting the electrical and myocardial substrates. Burgeoning epidemiological data have identified an increased risk for atrial fibrillation and sudden cardiac death related to OSA. Currently, few data exist to support the efficacy of OSA therapy, namely continuous positive airway pressure, as an adjunct for arrhythmia prevention or management.
RETRACTED: Evaluation of the Safety and Efficacy of Bremelanotide, a Melanocortin Receptor Agonist, in Female Subjects with Arousal Disorder: A Double-Blind Placebo-Controlled, Fixed Dose, Randomized Study
Authors: Safarinejad Mohammad Reza
Published: March 2008

This article has been retracted: please see Elsevier Policy on Article Withdrawal (https://www.elsevier.com/about/our-business/policies/article-withdrawal).

This article has been retracted at the request of the Editor-in-Chief. Following the retraction of Dr. Safarinejad's work by other journals, The Journal of Sexual Medicine has undertaken an extensive re-review of all papers Dr. Safarinejad published with the journal. Following an intensive re-evaluation and close scrutiny of the manuscripts, our expert reviewers raised multiple concerning questions about the methodology, results, and statistical interpretation as presented in this article. Dr. Safarinejad was contacted to provide his original data and offer explanations to address the concerns expressed by the reviewers. Dr Safarinejad chose not to respond. Consequently, we can no longer verify the results or methods as presented and therefore retract the article.
The Efficacy and Safety of Udenafil, a New Selective Phosphodiesterase Type 5 Inhibitor, in Patients with Erectile Dysfunction
Authors: Paick Jae-Seung , Kim Sae Woong , Yang Dae Yeol , Kim Ja Jong , Lee Sung Won , Ahn Tai Young , Choi Hyung Ki , Suh Jun-Kyu , Kim Sae Chul
Published: March 2008

Introduction

Udenafil is a potent selective phosphodiesterase type 5 (PDE5) inhibitor newly developed for the treatment of erectile dysfunction (ED).

Aim

This study was performed to evaluate the efficacy and safety of udenafil therapy in patients with ED.

Methods

In this multicenter, double-blind, placebo-controlled, fixed-dose, parallel-group phase III trial, 167 patients with ED of diverse origin and severity were randomized to take placebo or udenafil at fixed doses of 100 or 200 mg as needed for 12 weeks.

Main Outcome Measures

Primary efficacy variable was change from baseline in erectile function (EF) domain scores of the International Index of Erectile Dysfunction (IIEF) questionnaire. Secondary efficacy variables include change from baseline in scores on the IIEF Questions 3 and 4 (IIEF Q3 and Q4), change from baseline in all domain scores of the IIEF, patients' responses to questions 2 and 3 of the Sexual Encounter Profile (SEP2 and SEP3), and patients' responses to the Global Assessment Question (GAQ). Any adverse events were also recorded during the trial.

Results

After 12 weeks of treatment, the patients treated with udenafil showed significantly greater change from baseline in the IIEF-EF domain score compared with placebo (placebo, 0.20; 100-mg udenafil, 7.52; and 200-mg udenafil, 9.93, respectively) (P <0.0001). Compared with placebo, udenafil significantly enhanced the rates of successful penetration (SEP Q2) and maintenance of erection (SEP Q3) (P <0.0001). Furthermore, significantly greater proportions of udenafil treatment groups responded positively to the GAQ compared with the placebo group (GAQ: placebo, 25.9%; 100-mg udenafil, 81.5%; and 200-mg udenafil, 88.5%, respectively) (P <0.0001). Treatment-related adverse events were generally mild to moderate with facial flushing and headache being the most common.

Conclusions

Udenafil is an effective and well-tolerated therapy for ED of broad-spectrum etiology and severity.
The Sexual Lives of Medical Students: A Single Institution Survey
Authors: Shindel Alan W. , Ferguson Genoa G. , Nelson Christian J. , Brandes Steven B.
Published: March 2008

Introduction

Little is known about the personal sexual lives of medical students.

Aim

To assess sexual habits and determine the presence of sexual dysfunction among medical students.

Main Outcome Measures

Demographic and sexual experience data and domain scores on validated sexuality surveys. Instruments selected included the International Index of Erectile Function, the Index of Premature Ejaculation, and the Self Esteem and Relationship Quality Survey for male medical students and the Female Sexual Function Index (FSFI), and the Index of Sex Life for female medical students.

Methods

Medical students at our institution were invited to complete a demographic questionnaire and gender- appropriate sexuality surveys. Results were compared with established normative data and validated cut-off scores when available. Linear regression and Pearson coefficient were used to assess relationships between variables.

Results

There were 132 responses (78 female mean age 24 years, 54 male, mean age 25 years). Condoms and oral contraceptives were the most popular form of contraception. Among men, 81.5%, 37%, and 93% were in a relationship, married, and heterosexual, respectively. Among women, 64%, 18%, and 95% were in a relationship, married, and heterosexual. Erectile dysfunction was reported by 30% of men. Proxy measures of other sexual problems in men revealed a 28% prevalence of dissatisfaction with sex life, a 28% prevalence of problems controlling ejaculation, an 11% prevalence of orgasmic dysfunction, and a 6% prevalence of low sexual desire. Based on validated FSFI scoring, 63% of women were at high risk of sexual dysfunction. Proxy measures of other problems in women indicated disorders of pain, orgasms, desire, sex satisfaction, lubrication, and arousal in 39%, 37%, 32%, 28%, 26%, and 24% of female respondents, respectively.

Conclusions

These data provide insight into the sexual lives of medical students. Rates of sexual dysfunction are higher than expected based on normative data. Further research is required.
Restoration of Female Genital Vasocongestive Arousal Responses in Young and Aged Rats
Authors: Beharry Rochard K.S. , Hale Taben M. , Heaton Jeremy P.W. , Shamloul Rany , Adams Michael A.
Published: March 2008

Introduction

Treatments of aged, male hypertensive rats that induce vascular remodeling or that normalize endothelial function are known to produce sustained improvements in erectile function. Whether the treatments targeting these processes benefit female genital vasocongestive arousal (GVA) responses is currently not known.

Aim

To determine whether the actions of nitric oxide (NO) are critical to the apomorphine (APO)-generated GVA responses in both intact and ovariectomized OVX young adult female rats (before any aging-associated decreases in the responses). In addition, we also investigated whether the diminished GVA responses in aged rats could be restored, at least in part, using an antihypertensive treatment, which is known to enhance erectile responses and improve general vascular function in male rats.

Methods

In female Wistar rats, APO-induced GVA responses (80 µg/kg, subcutaneously [sc], 30 minutes) were assessed by videomonitoring following various treatments. Young adult females were ovariectomized or were treated with the nitric oxide synthase (NOS) inhibitor N-nitro-L-arginine methyl ester (30 mg/kg, iv), followed by an NO mimetic, sodium nitroprusside (10 µg/kg/minute, intravenous). Aged females (18 months) were treated for 2 weeks with the angiotensin converting enzyme (ACE) inhibitor, enalapril (30 mg/kg/day, orally) plus low sodium (0.04%).

Main Outcome Measures

APO-induced GVA responses in female rats.

Results

There was an age-associated reduction in sexual responses in normotensive rats that was greatly enhanced (fourfold) by brief, aggressive antihypertensive treatment. The enhanced vasocongestive responses persisted for a 5-week off-treatment. Both OVX and NOS inhibition significantly decreased sexual responses by approximately 80% in young female rats. Systemic administration of an NO mimetic recovered vasocongestive responses in the NOS-blocked rats, but not in OVX animals.

Conclusions

Although mechanisms were not established, the major findings were that brief aggressive ACE inhibitor treatment markedly improved sexual responses in aged female rats, and systemic delivery of an NO mimetic recovered sexual responses in globally NOS-blocked animals.
Combination of Alfuzosin and Tadalafil Exerts In Vitro an Additive Relaxant Effect on Human Corpus Cavernosum
Authors: Oger Stephanie , Behr-Roussel Delphine , Gorny Diane , Charles Tremeaux Jack , Combes Michel , Alexandre Laurent , Giuliano François
Published: March 2008

Introduction

Phosphodiesterase type 5 (PDE5) inhibitors, such as tadalafil, are a first-line treatment for erectile dysfunction (ED). Nevertheless, some patients do not respond to this treatment. Clinical data suggest that the addition of α1-adrenoceptor blocker, such as alfuzosin, commonly prescribed for lower urinary tract symptoms suggestive of benign prostatic hyperplasia, may be of benefit.

Aim

Evaluation of the effect of alfuzosin, tadalafil or the combination of both on human corpus cavernosum.

Methods

Human cavernosal tissues were obtained from 10 patients undergoing penile surgery. Strips contractility was studied in organ baths. Concentration–response curves to tadalafil were generated on norepinephrine (NE, 1–10 µM)-precontracted strips in the presence of alfuzosin or vehicle. Frequency–response curves (FRC) to electrical field stimulation (EFS, 0–64 Hz, 3 ms, 10 seconds, 300 mA) were generated in the presence of vehicle, alfuzosin, tadalafil, or both drugs combined. EFS (20 Hz, 1 ms, 10 seconds, 300 mM)-induced nitrergic relaxation on NE-precontracted strips was studied in the presence of vehicle, alfuzosin, tadalafil, or both drugs combined.

Main Outcome Measures

Functional measurement of cavernosal smooth muscle relaxation in the presence of tadalafil and alfuzosin.

Results

The relaxation induced by tadalafil (10−10 to 10−5 M) on precontracted strips was enhanced by alfuzosin at both 10−8 and 10−7 M. The combination of alfuzosin (3.10−8 M) and tadalafil (10−7 M) was more efficient to inhibit FRC-induced contractions than each compound alone. The combination of tadalafil (10−6 M) and alfuzosin (10−8 M) increased the relaxation induced by EFS and its effect was greater than tadalafil alone. In addition, the combination of tadalafil (10−6 M) and alfuzosin (10−7 M) prolonged EFS-induced relaxation to a greater extent than each compound alone.

Conclusions

In vitro, the combination of alfuzosin and tadalafil is more efficient than each compound alone to relax adrenergic tone or to enhance nitrergic relaxation of the human corpus cavernosum. Such a combination deserves further investigation in placebo-controlled studies to evaluate its benefit in ED patients who are not sufficiently improved by PDE5 inhibitors.
Clinical Female Sexual Outcome after Sacral Neuromodulation Implant for Lower Urinary Tract Symptom (LUTS)
Authors: Lombardi Giuseppe , Mondaini Nicola , Macchiarella Angelo , Cilotti Antonio , Popolo Giulio Del
Published: March 2008

Introduction

Over the last few years, sacral neuromodulation (SNM) has become an established treatment option for lower urinary tract symptoms (LUTS).

Aim

To evaluate if SNM improves sexual function in females treated with SNM for LUTS.

Main Outcome Measures

Improvement in sexuality by the Female Sexual Function Index (FSFI) and the Female Sexual Distress Score (FSDS).

Materials and Methods

We included 31 women, 17 of whom were neurogenic with permanent SNM. Prior to the neuromodulation screening, we assessed sexual function through blood sexual hormones, the FSFI and the FSDS questionnaires. Significant enhancement in sexuality meant an increase of 60% of the total score or of one FSFI domain, or 50% improvement on the FSDS. Only females who showed significant benefits in the first visit post-permanent SNM repeated the questionnaires in follow-up. All these women had their final visit by July 2007.

Results

Both questionnaires indicated a clinically significant improvement in sexuality that was maintained up to the final visit for 4 out of 11 neurogenics with sexual dysfunctions: one showed arousal and desire disorders, one showed arousal disorder and lubrication impairment, one showed arousal disorder and pain, and one showed desire and orgasm deficits. Mean duration of sexual improvement was 23 months. Notable clinical improvement in sexuality was observed in two out of eight idiopathics (one suffering from arousal and desire disorders, and one from lubrication impairment) with a median follow-up of 22 months.

Conclusions

The positive effects regarding sexuality may be due either to enhancement of LUTS or to the direct stimulation of the sacral roots (S3).
BIOSYNTHETIC INCORPORATION OF M‐FLUOROTYROSINE INTO BACTERIORHODOPSIN
Authors: Hazard E. Starr , Govindjee Rajni , Ebrey Thomas G. , Crouch Rosalie K.
Published: March 2008

Abstract— Halobacterium halobium, grown in a defined medium where tyrosine had been largely replaced with m‐fluorotyrosine, biosynthetically produced purple membrane. Analysis of this membrane by high pressure liquid chromatography of phenylthiocarbamyl derivatized amino acids of membrane acid hydrolysates revealed that up to 50% of the tyrosine was present as the m‐fluorotyrosine form. Yields of the purple membrane decreased as the level of incorporation increased. The experimental purple membrane showed a single 19F NMR resonance at ‐61.983 ppm (relative to trifluoroacetic acid). The bacteriorhodopsin (bR) in the purple membrane was normal as assayed by gel electrophor‐esis, isoelectric focusing, circular dichroic spectra, and UV‐visible spectra. However, the fluorinated tyrosine bacteriorhodopsins at near neutral pH exhibited slightly slower rates of proton uptake and a slower M‐state decay with biphasic kinetics reminiscent of alkaline solutions of bR (pH > 9). These results imply that the tyrosines in bacteriorhodopsin may play a role in the photoactivated proton translocation process of this pigment.
SPIN LABELED CYSTEINES AS SENSORS FOR PROTEIN‐LIPID INTERACTION AND CONFORMATION IN RHODOPSIN
Authors: Farahbakhsh Zohreh T. , Altenbach Christian , Hubbell Wayne L.
Published: March 2008

Abstract—In stoichiometric amounts, the spin label N‐tempoyl‐(p‐chloromercuribenzamide) reacts rapidly with one cysteine residue in membrane‐bound bovine rhodopsin. This residue is distinct from the two reactive cysteines previously used as attachment sites for spectroscopic labels, and is on the external surface of the protein near the cytoplasmic membrane/aqueous interface.

The spin‐labeled side chain has revealed a light‐induced conformational change in membrane‐bound rhodopsin that is apparently not associated with protein aggregation. The changes are reversible upon the addition of 11‐cis retinal, and the magnitude of the change is dependent on the identity of the phospholipid in the surrounding bilayer. Alteration of lipid composition has a much larger effect on bleached rhodopsin than rhodopsin itself, indicating that the former is more readily deformable in response to changes in bilayer properties. This is consistent with the loss of 11‐cisretinal binding energy in opsin compared to rhodopsin. These results provide direct structural evidence that the conformation of a membrane protein can be modulated by the lipid properties.
FORMATION AND DECAY KINETICS OF BACTERIORHODOPSIN'S N INTERMEDIATE: SOFTENING THE PROTEIN CONFORMATION WITH ALCOHOLS AFFECTS INTRA‐PIROTEIN PROTON TRANSFER AND RETINAL ISIOMERIZATION
Authors: Fukuda Kazuya , Kouyama Tsutomu
Published: March 2008

Abstract— The trans photocycle of bacteriorhodopsin was investigated in the presence of organic solvents with a hydrogen‐bonding group; i.e. methanol, ethanol, 1‐propanol and so on. These alcohols scarcely or only slightly affected the L→M and Ob̊570 transitions, but they perturbed the M→N and N→O transitions greatly. The rate of the M→N transition increased linearly with increasing alcohol concentration and, at maximal alcohol concentrations under which the native protein conformation was retained, the M→N transition was accelerated by a factor of ∼5. This alcohol effect was reversible. It is suggested that a long‐distance proton transfer involved in the M→N transition (Asp.96→retinal) becomes easier when the protein conformation is softened bv partially breaking hydrogen‐bonding networks in the protein. Another significant effect of alochol is inhibition of the N→O transition at weakly acidic pH, which was slowed down maximally by a factor of ˜10. This alcohol effect was less significant at alkaline pH, where reprotonation of Asp‐96 from the cytoplasmic membrane surface is a rate‐limiting reaction. It is suggested that, at acidic pH, thi: cis‐to‐trans isomerization involved in the N→O transition is a rate‐limiting reaction and that this step is inhibited in the presence of a high concentration of alcohols.
STRUCTURE OF HYPSORHODOPSIN: ANALYSIS BY FOURIER TRANSFORM INFRARED SPECTROSCOPY AT 10 K
Authors: Sasaki Jun , Maeda Akio , Shichida Yoshinori , Groesbeek Michel , Lugtenburg Johan , Yoshizawa Tôru
Published: March 2008

Abstract—Vibrational bands of hypsorhodopsin in the difference Fourier transform infrared spectra were identified as the bands which arose after formation of isorhodopsin by successive irradiations of bovine rhodopsin at 10 K with >500 nm light, and also as the bands disappeared upon conversion to bathorhodopsin by warming. The chromophore bands were assigned by the bands which shifted upon deuterium substitution of the polyene chain of the retinylidene chromophore. The presence of chromophore bands which shift by D2O exchange clearly shows that the Schiff base chromophore of hypsorhodopsin is protonated. The amide I bands and several other protein bands of hypsorhodopsin appeared at the same frequencies as those of bathorhodopsin, but they are different from those of rhodopsin and isorhodopsin. Furthermore, like bathorhodopsin, hypsorhodopsin displays the Cl—H out‐of‐plane bending mode which is weakly coupled with C12‐‐–H out‐of‐plane mode. These facts show that hypsorhodopsin has a chromophore conformation and chromophore‐opsin interaction more similar to bathorhodopsin than to rhodopsin and isorhodopsin.
ULTRAVIOLET RESONANCE RAMAN STUDY ON PURPLE AND BLUE MEMBRANES OF Halobacterium halobium
Authors: Hashimoto S. , Miura K. , Yamagishi T. , Takeuchi H. , Harada I.
Published: March 2008

Abstract— Two hundred and forty and 213 nm excited resonance Raman spectra of purple membrane (PM) and blue membrane (BM) of Halobacterium halobiurn were studied. Generally intense Trp scattering and a strong relative intensity of the W3 band at 1553 cm‐1 in the 240 nm spectrum of PM indicate red‐shifted Bb absorptions of some Trp sidechains. A high intensity ratio of Trp doublet at 1360 and 1340 cm‐1 suggests interactions with highly hydrophobic Trp environments. These Trp are not strongly H‐bonded and their N1 sites are located in positions easily reached by solvent water molecules. Tyrosines are also in very hydrophobic environments and H‐bonded. The mainchain consists of normal and distorted α‐helices whose amide NH are hardly deuterated in D2O suspension, and some NH exchangeable irregular segments on the membrane surface. Upon acidification, the ratio of Trp doublet with 240 nm excitation decreases concomitant with increase in retinal absorbance at 600 nm, and the W3 relative intensity and overall Trp scattering also decrease. These observations strongly indicate that the counterpart of Trp interactions in PM is the retinal and that the interactions partly diminish upon acidification. The Tyr environment also changes with the color. Although the 240 nm amide I intensity is greater in acid BM than in PM, the change is not related to the color change because the amide I intensity of deionized BM is practically the same as that of PM. The amide I intensity increase in acid BM is ascribable to a structural change of the surface peptides due to acid induced aggregation.
NANOSECOND LASER PHOTOLYSIS OF PHOBORHODOPSIN: FROMNatronobacterium pharaonisAPPEARANCE OF KL AND L INTERMEDIATES IN THE PHOTOCYCLE AT ROOM TEMPERATURE
Authors: Imamoto Yasushi , Shichida Yoshinori , Hirayama Junichi , Tomioka Hiroaki , Kamo Naoki , Yoshizawa Tôru
Published: March 2008

Abstract—Photochemical and subsequent thermal reactions ofpharaonisphoborhodopsin (ppR; absorption maximum, 498 nm) fromNatronobacrerium pharaoniswere investigated by nanosecond laser photolysis at 20°C. The experimental results clearly showed the presence of two intermediates in the photocycle of ppR besides the K, M and O intermediates detected previously. One was formed immediately after the excitation of ppR with a blue pulse (pulse width, 17 ns; wavelength, 460 nm), and the other was formed by the thermal reaction of this species. The new intermediates' absorption maxima were 512 and 488 nm, their extinction coefficients were 0.85‐ and 0.68‐times smaller than that of ppR, and their lifetimes were 990 ns and 32 μs, respectively. The absorption and kinetic characteristics of these intermediates relative to ppR were similar to those of the KL and L intermediates of bacteriorhodopsin (bR). The formation of KL intermediates from both ppR and bR were observed only at room temperatures. On the other hand, the formation of L intermediate of bR was observed at both of room and low temperature, whereas that from ppR only at room temperature. The unique formation of L intermediate of ppR at room temperature is discussed in relation to high thermal stability of K intermediate of ppR.
PHOTOLYSIS OF RHODOPSIN RESULTS IN DEPROTONATION OF ITS RETINAL SCHIFF'S BASE PRIOR TO FORMATION OF METARHODOPSIN II
Authors: Thorgeirsson Thorgeir E. , Lewis James W. , Wallace‐Williams Stacie E. , Kliger David S.
Published: March 2008

Abstract—Absorption changes following photolysis of bovine rhodopsin in mildly sonicated membrane suspensions are monitored at 25°C. Difference spectra collected at 17 times between 1 μs and 75 ms following excitation are analyzed globally using singular value decomposition and non‐linear least‐squares fitting techniques. The results are not consistent with the simple scheme: Lumirhodopsin → Metarhodopsin I → Metarhodopsin II, but indicate that an intermediate with a deprotonated Schiff's base is formed nearly simultaneously with Metarhodopsin I upon the decay of Lumirhodopsin.
MOLECULAR MECHANISMS IN VISUAL PIGMENT REGENERATION
Authors: Rando Robert R.
Published: March 2008

Abstract—The photochemical bleaching of vertebrate rhodopsin results in thecistotransisomerization of the 11‐cis‐retinal protonated Schiff base. Hydrolysis of the Schiff base leads to the formation of opsin and all‐trans‐retinal. In order for vision to proceed, the enzymatictranstocisisomerization of a retinoid must occur. Since retinoids exist as alcohols, aldehydes, or esters in the eye, there are potentially nine different routes for isomerization. Moreover, 11‐cis‐retinoids are approximately 4 kcal/mol higher in energy than their all‐transisomers. Thus, not only must the isomerization route be defined, but an energy source must be identified to power this process. It was discovered that the energy is provided for in a minimally two‐step process involving membrane phospholipids as the energy source. First, all‐trans‐retinol (vitamin A) is esterified in the retinal pigment epithelium by lecithin retinol acyl transferase to produce an all‐trans‐retinyl ester. Second, this ester is directly transformed into 11‐cis‐retinol by an isomerohydrolase enzyme, in a process that couples the negative free energy of hydrolysis of the acyl ester to the formation of the strained 11‐cis‐retinoid.
INTERACTION OF RHODOPSIN, G‐PROTEIN AND KINASE IN OCTOPUS PHOTORECEPTORS
Authors: Tsuda Motoyuki , Hirata Hajime , Tsuda Tomoko
Published: March 2008

Abstract— Light induced phosphorylation of octopus rhodopsin was greatly enhanced by guanosine 5′‐O‐(3‐thiotriphosphate) (GTPγS), suggesting that the kinases are involved in regulating interaction between rhodopsin and G‐protein. We determined phosphorylated peptides of octopus rhodopsin in the presence or absence of GTPγS. Possible phosphorylation sites for octopus rhodopsin enhanced by GTPγS were Thr329, Thr330 and/or Thr336, which suggest that the G‐protein associates with cytoplasmic loops including C‐terminal peptide in the seventh helix of octopus rhodopsin.
Measurement of ionized calcium in canine blood samples collected in prefilled and self‐filled heparinized syringes using the i‐STAT point‐of‐care analyzer
Authors: Tappin Simon , Rizzo Francesca , Dodkin Steve , Papasouliotis Kostas , Tasker Séverine , Murphy Kate
Published: March 2008

Background:Heparinized syringes are commonly used with point‐of‐care analyzers (eg, i‐STAT) to measure ionized calcium (iCa2+); however there is little information about the validity of their use in canine patients.

Objective:To examine the suitability of prefilled (40 IU heparin/mL) and self‐filled (150 IU heparin/mL) heparinized syringes for iCa2+measurements using the i‐STAT analyzer.

Methods:Forty‐seven blood samples were collected from 41 canine patients. Two milliliters of blood were collected into a 2‐mL nonanticoagulated (NA) syringe, a commercially available preheparinized (PH) syringe (dry calcium‐balanced lithium heparin, 40 IU/mL), and a 2‐mL self‐filled heparinized (SH) syringe (liquid sodium heparin, 150 IU/mL). iCa2+was measured in the sample using the i‐STAT analyzer and a wet‐reagent analyzer (KoneLab 30i) used as the reference instrument. Data were analyzed using pairedt‐tests, Pearson correlation coefficient, and Bland‐Altman difference plots.

Results:There was no significant difference between the results obtained from NA and PH syringes using the i‐STAT analyzer, and the correlation was excellent (r=.97). The i‐STAT values from the SH syringes (mean, 1.07 mmol/L) were significantly lower (P<.001) than those from the NA syringes (mean, 1.38 mmol/L). iCa2+was significantly higher with the i‐STAT analyzer than with the KoneLab analyzer for both the PH (mean i‐STAT, 1.38 mmol/L vs mean KoneLab, 1.30 mmol/L) and SH (mean i‐STAT, 1.07 mmol/L vs mean KoneLab, 1.03 mmol/L) samples.

Conclusions:Blood samples collected in the PH syringes used in this study can be used interchangeably with those collected in NA syringes for measuring iCa2+using the i‐STAT analyzer. SH syringes with high‐concentration heparin products (5000 IU/mL) are unsuitable for measuring iCa2+because they cause clinically significant underestimations. Although there was good correlation between the i‐STAT and KoneLab analyzers, the results should be interpreted using analyzer‐specific reference intervals.
Optimization and validation of a flow cytometric method for immunophenotyping peripheral blood lymphocytes from cynomolgus monkeys (Macaca fascicularis)
Authors: Baker Deanna L. , Finco‐Kent Deborah L. , Reagan William J. , Conklyn Maryrose J. , Kawabata Thomas T.
Published: March 2008

Background: Guidelines published by the Food and Drug Administration and Center for Human Medicinal Products describe the need to assess immunotoxic effects in nonclinical studies that evaluate drug toxicity, including the use of immunophenotyping to measure immunotoxicity. We are not aware of previous studies, however, that have validated methods for immunophenotyping peripheral blood lymphocyte subsets in whole blood samples from cynomolgus monkeys.

Objective: The purpose of this study was to optimize and validate a flow cytometric assay for immunophenotyping lymphocytes in the peripheral blood of cynomolgus monkeys.

Methods: A series of prevalidation experiments were done to determine optimal reagents, volumes, timing, and other procedural details of the flow cytometric assay. Using the optimized method, we then determined precision, interindividual variation, laboratory‐to‐laboratory variability, and sample stability. Stabilized human blood was used as a positive control for staining, processing, and analysis. The percentage and number of pan‐T cells (CD3+), T‐helper cells (CD3+4+), T cytotoxic/suppressor cells (CD3+8+), natural killer cells (CD3−16+), and B‐cells (CD3−20+) were determined in 146 male and 140 female, clinically healthy monkeys and reference intervals were calculated.

Results: By doing 4‐color staining with a lyse‐wash method, intra‐ and interassay precision were <5% for all lymphocyte subsets. Variability between technicians and laboratories was minimal (CVs<3%). Samples were stable for up to 24 hours after staining and fixing.

Conclusions: The validated method is extremely robust and can be performed under good laboratory practice conditions to support nonclinical studies. Reference intervals for lymphocyte subsets were similar to those previously reported.
What is your diagnosis? Lingual mass in a dog
Authors: Chapman Seth , Nabity Mary , Calise David
Published: March 2008

Abstract:A 3.5‐year‐old female spayed Rat Terrier was presented for evaluation of a submucosal lingual mass. Fine‐needle aspiration of the mass revealed a population of neoplastic cells composed predominantly of small, round cells and large, round to spindle‐shaped cells, which occasionally had blunt cytoplasmic borders and multiple nuclei. The neoplastic cells had moderate to marked anisocytosis and anisokaryosis. The cytologic interpretation was malignant neoplasia, most likely sarcoma. Histopathologic examination of a biopsy specimen revealed an unencapsulated, poorly demarcated, moderately cellular neoplasm composed of individualized, infiltrative spindle cells. Elongate skeletal muscle cells with prominent, rectangular borders (strap cells) were observed. A morphologic diagnosis of rhabdomyosarcoma was made. Staining with phosphotungstic acid–hematoxylin revealed haphazardly arranged skeletal muscle cross‐striations. Immunohistochemical staining results for vimentin, Myo D1, desmin, and myoglobin were positive, though staining intensity of tumor cells varied with the degree of differentiation. Using transmission electron microscopy, irregular, disorganized Z‐bands were identified. Rhabdomyosarcomas are uncommon tumors in the dog, and rarely may involve the tongue or oral cavity. Cytologic evaluation of a rhabdomyosarcoma may reveal a pleomorphic population of cells and definitive diagnosis may require histologic examination, immunohistochemical staining, and electron microscopy.
SEMICONDUCTOR DEVICE SCALING: PHYSICS, TRANSPORT, AND THE ROLE OF NANOWIRES
Authors: FERRY D. K. , AKIS R. , GILBERT M. J. , CUMMINGS A. , RAMEY S. M.
Published: March 2008

Nanoelectronics (including nanomagnetics and nanophotonics) generally refers to nanometer scale devices, and to circuits and architectures which are composed of these devices. Continued scaling of the devices into the nanometer range leads to enhanced information processing systems. Generally, this scaling has arisen from three major sources, one of which is reduction of the physical gate length of individual transistors. Until recently, this has also allowed an increase in the clock speed of the chip, but power considerations have halted this to levels around 4 GHz in Si. Indeed, there are indications that scaling itself may be finished by the end of this decade. Instead, there are now pushes to seek alternative materials for nano-devices that may supplement the Si CMOS in a manner that allows both higher speeds and lower power. In this paper, we will cover some of the impending limitations, and discuss some alternative approaches that may signal continued evolution of integrated circuits beyond the end of the decade.