bluuebunny/crossref_metadata_2025 huggingface dataset:
Ubiquitin‐positive inclusions and progression of pathology in frontotemporal dementia and motor neurone disease identifies a group with mainly early pathology
Authors: Kersaitis C. , Halliday G. M. , Xuereb J. H. , Pamphlett R. , Bak T. H. , Hodges J. R. , Kril J. J.
Published: October 2005

Frontotemporal lobar degeneration (FTLD) with tau‐negative, ubiquitin‐positive inclusions has been a topic of major interest in recent years, with this group now accounting for the majority of tau‐negative cases of frontotemporal degeneration. The severity of neurodegeneration in FTLD is dependent on the stage of disease and is substantial even in the earliest stages. Elucidating the pathogenesis of FTLD requires evaluation of changes during the earliest possible stage of disease. However, the long survival of most frontotemporal dementia cases means that cases with early neuropathology are not frequently encountered. Cases of FTLD with the shortest survival are those with coexisting motor neurone disease (FTLD + MND), making these the ideal group for studying early FTLD pathology. It is not clear, however, what the pathological contribution of MND is in these cases. This study evaluates the pathology of 20 cases of FTLD (11 with no clinical signs of MND and nine with FTLD + MND) as well as 10 cases of MND without dementia. Our findings indicate that the deposition of ubiquitin does not play a key role in the neurodegenerative process in FTLD, and that the severity of neurodegeneration in FTLD is similar in cases with and without clinical MND.
Reliability Evaluation of Sampling Plan Fixed by Council Directive 91/68/EEC for the Maintenance of Officially Brucellosis‐free Flock Status
Authors: De Massis F. , Petrini A. , Giovannini A.
Published: October 2005

The European Union (EU) strategy with respect to sheep and goat brucellosis aims to eradicate the infection and achieve officially brucellosis‐free (OBF) status in all EU holdings and territories. Council Directive 91/68/EEC of 28 January 1991 states that to maintain OBF status of ovine or caprine holdings located outside an OBF territory, only a representative number of animals need to be tested annually. However, depending on the number of animals in a holding, this testing method risks non‐detection of the infection, thereby reducing the efficacy of the brucellosis control plan. The recommended sampling procedure has a low sensitivity for detecting infection in medium‐sized flocks; furthermore, the risk of not detecting re‐infection in OBF flocks, particularly in territories that have not yet gained OBF status, is also not acceptable. Moreover, in large‐sized flocks, the Directive sampling procedure entails taking an excessive number of samples, which can be very expensive. The authors evaluated, by using statistical analyses and a simulation model based on field data, the possible consequences of the current EU strategy. It is suggested that the sampling criteria for the maintenance of OBF status in the EU should be modified and that a statistically based sampling method should be applied instead of the fixed percentage method that is currently in use.
Recognition of a B‐cell Epitope of the VapA Protein ofRhodococcus equiin Newborn and Experimentally Infected Foals
Authors: Phumoonna T. , Barton M. D. , Heuzenroeder M. W.
Published: October 2005

The aim of this study was to evaluate the usefulness of the previously identified B‐cell epitope TSLNLQKDEPNGRASDTAGQ of the VapA protein ofRhodococcus equiand its association withR. equipneumonia. A modified peptide designated PN11‐14 corresponding to the epitope was recognized by all sera from experimentally infected foals with virulentR. equiATCC103+containing the virulence plasmid but not by its plasmid‐cured derivative ATCC103−strain. Marked levels of VapA‐specific immunoglobulin (Ig)G were detected in all sera from the ATCC103+infected foals at 2 weeks after the infection. One control animal had high titres as determined by the peptide enzyme‐linked immunosorbent assay (ELISA), indicating the ELISA may not absolutely differentiate between foals withR. equipneumonia and healthy exposed foals in farms where the prevalence of disease is high. However, numbers of animals used were small. Further evaluation of the peptide ELISA with field samples is necessary to determine whether the assay is diagnostically useful. This study showed that levels of passive transfer of maternal IgG antibodies to the epitope in newborn foals could be measured. Interestingly, the maternally derived antibodies were found to significantly (P < 0.05 by Student'st‐test) decline 2 weeks after birth. Seroconversion against naturally occurring VapA expressingR. equicould be detected in some foals at 4 weeks of age. Antibodies to the epitope peaked and were significantly (P < 0.05) greater in foals aged between 6 and 8 weeks. These results indicated that the peptide ELISA could be used to monitor anti‐VapA antibodies in foals, particularly those at the age of 4–6 weeks. It is possible that the ELISA may be of some use as a diagnostic test on farms whereR. equiis non‐endemic. Further studies using large number of field samples are needed to verify this assumption.
Zero tolerance ecology: improving ecological inference by modelling the source of zero observations
Authors: Martin Tara G. , Wintle Brendan A. , Rhodes Jonathan R. , Kuhnert Petra M. , Field Scott A. , Low‐Choy Samantha J. , Tyre Andrew J. , Possingham Hugh P.
Published: October 2005

A common feature of ecological data sets is their tendency to contain many zero values. Statistical inference based on such data are likely to be inefficient or wrong unless careful thought is given to how these zeros arose and how best to model them. In this paper, we propose a framework for understanding how zero‐inflated data sets originate and deciding how best to model them. We define and classify the different kinds of zeros that occur in ecological data and describe how they arise: either from ‘true zero’ or ‘false zero’ observations. After reviewing recent developments in modelling zero‐inflated data sets, we use practical examples to demonstrate how failing to account for the source of zero inflation can reduce our ability to detect relationships in ecological data and at worst lead to incorrect inference. The adoption of methods that explicitly model the sources of zero observations will sharpen insights and improve the robustness of ecological analyses.
Molecular mechanisms of lipid‐induced insulin resistance in muscle, liver and vasculature
Authors: Krebs M. , Roden M.
Published: October 2005

Abstract:  Increased body fat content correlates with insulin resistance and is a key feature of type 2 diabetes. Excessive intake of fat results in deposition of lipids not only in fat tissue but also in skeletal muscle and liver. Subsequently, both plasma and intracellular concentrations of free fatty acids and their metabolites rise and activate signal transduction pathways, which will induce inflammation and impair insulin signalling. Furthermore, elevated circulating lipids impair endothelial function and fibrinolysis, which contributes to the development of vascular disease. Thus, therapeutic strategies aiming at reduction of (intracellular) lipid availability in skeletal muscle and liver and pharmacological modulation of the signalling pathways activated by increased lipid stores represent promising targets for future treatment of insulin resistance and prevention of its complications. This review focuses on the effects of increased lipid availability on the regulation of glucose metabolism in skeletal muscle and liver as well as on vascular function.
The DIACOM study (effect of DosIng frequency of oral Antidiabetic agents on the COMpliance and biochemical control of type 2 diabetes)
Authors: Kardas P.
Published: October 2005

Aim:  Sulphonylureas are widely used in the management of type 2 diabetes. The effectiveness of treatment with oral antidiabetic drugs depends largely on patient compliance. The objective of the DIACOM (effect of DosIng frequency of oral Antidiabetic agents on the COMpliance and biochemical control of type 2 diabetes) study was to compare the compliance of patients treated with once‐daily (od) or twice‐daily (bid) sulphonylureas.

Methods:  One hundred and five patients, previously treated with glibenclamide, were randomized to receive gliclazide in modified‐release formulation (MR) once daily or glibenclamide twice daily for 16 weeks, using an electronic monitoring system (MEMS®).

Results:  A significant difference in compliance was observed between the two groups. The overall compliance was 93.5 ± 14.0% in the once‐daily gliclazide MR group and 87.2 ± 21.1% in the twice‐daily glibenclamide group (p < 0.05), and the correct number of doses was taken on 86.3 ± 15.4 and 66.9 ± 29.0% of treatment days respectively (p < 0.0001). The percentage of missed doses was 9.3 ± 12.5% in the once‐daily group and 17.5 ± 18.0% in the twice‐daily group (p < 0.01). The percentage of doses taken in the correct time window and correct interdose interval was higher in the once‐daily group, as was therapeutic coverage. Patients in the gliclazide MR group also achieved significantly better glycaemic control [fasting plasma glucose and glycated haemoglobin (HbA1c)] than those treated with glibenclamide (p < 0.0001).

Conclusions:  The study demonstrates that patient compliance with once‐daily gliclazide MR is significantly better than with twice‐daily glibenclamide. Consistently better efficacy was observed for short‐term (fasting glucose) and long‐term glycaemic control (HbA1c) in the once‐daily group. These results demonstrate the possible therapeutic advantages of once‐daily agents over twice‐daily agents in the treatment of type 2 diabetes.
Relationship between pedometer‐registered activity, aerobic capacity and self‐reported activity and fitness in patients with type 2 diabetes
Authors: Bjørgaas M. , Vik J. T. , Sæterhaug A. , Langlo L. , Sakshaug T. , Mohus R. M. , Grill V.
Published: October 2005

Aim:  The aim of this study is to investigate the relationship between pedometer‐registered activity, aerobic capacity (VO2max) and self‐reported activity and fitness in patients with type 2 diabetes before and after a 12‐week exercise programme.

Methods:  Twenty‐nine men with type 2 diabetes (age = 57.4 (7.8) years, BMI = 31.7 (2.8) kg/m2) underwent exercise testing, registered pedometer activity and reported their physical fitness and activity in a questionnaire. Participants were randomly allocated to an exercise (EX) group (n = 15) or a control (CO) group (n = 14). Participants in EX group were offered supervised exercise twice a week for 12 weeks. At the end of the study, participants again underwent exercise testing, fasting blood tests and registration of pedometer activity.

Results:  At baseline, pedometer activity correlated with VO2max (r = 0.43, p = 0.02) and with perceived physical fitness (r = 0.48, p = 0.02). After, but not before, intervention, pedometer activity and VO2max additionally correlated with perceived everyday activity (r = 0.62, p < 0.01 and r = 0.49, p = 0.03, respectively). Both EX and CO groups tended to increase pedometer activity. In EX group, weight decreased by 2.7% (p = 0.01), VO2max increased 10.6% (p = 0.03) and HbA1c decreased by 5.2% from baseline (p = 0.02). In EX group, an increase in pedometer activity correlated with a fall in HbA1c (r = 0.84, p < 0.01) and in diastolic blood pressure (r = 0.77, p = 0.025).

Conclusions:  Pedometer activity correlates with VO2max in type‐2 diabetic patients. Our exercise programme was well tolerated; it produced favourable effects on body weight, aerobic capacity and metabolic control. The use of pedometer may lead to more realistic assessment of perceived everyday physical activity.
Pharmacologic modifications of hormones to improve their therapeutic potential for diabetes management
Authors: Garber Alan J.
Published: October 2005

Rapid‐acting genetically engineered insulin analogues emerging in the last 10 years are now established as more effective prandial insulins than traditional short‐acting human insulin. The development of analogues for use as basal insulin, however, has been much slower. Methods of protracting the time–action curve of injected insulin include complexing with proteins, insulin crystal formation, shifting the iso‐electric point of the amino acid sequence or attaching a fatty‐acid side chain to the molecule. The latter two methods have been more successful in producing physiologic insulin profiles when compared with the former methods. The principle of acylation has also been applied to prolong the action of other hormones, such as glucagon‐like peptide 1 (GLP‐1), as the native peptide has a very short half‐life. Preliminary results with this compound and other GLP‐1 analogues show promise in treating patients with type 2 diabetes. In summary, the development of new insulin and other hormone preparations by the manipulation of native peptide structure has recently improved our antidiabetic armamentarium, and further research will continue this fruitful approach.
Low‐Density Lipoprotein Cholesterol and Mortality in Older People
Authors: Tikhonoff Valérie , Casiglia Edoardo , Mazza Alberto , Scarpa Roberta , Thijs Lutgarde , Pessina Achille C. , Staessen Jan A.
Published: October 2005

Objectives: To investigate the role of low‐density lipoprotein cholesterol (LDL‐C) as a predictor of mortality in elderly subjects.

Design: Population‐based prospective cohort study.

Setting: Two communities in northern Italy.

Participants: Three thousand one hundred twenty Caucasian subjects aged 65 and older recruited in for the Cardiovascular Study in the Elderly and followed up for 12 years.

Measurements: Anthropometric measures: fasting plasma total cholesterol, triglyceride, high‐density lipoprotein cholesterol, LDL‐C, glucose, creatinine, and body mass index. Clinical measures: medical assessment, diabetes mellitus, hypertension, stroke, coronary disease, heart failure, and smoking and drinking habits. Vital status measures: death certificates from the Registry Office and causes of death according to the International Classification of Diseases. After plotting mortality rates using quartiles of LDL‐C, relative hazard rates (RHRs) were calculated using multivariate Cox regression analyses. When the trend was nonlinear, the RHRs were further calculated for the 25th, 50th, and 75th percentiles of the distribution to confirm curvilinearity.

Results: The distribution of risk of total mortality in women and of fatal heart failure in all subjects was curvilinear (non J‐shaped), decreasing nonlinearly with LDL‐C. For total mortality in men and cardiovascular mortality in both sexes, the relationship with LDL‐C was J‐shaped. The risk of fatal myocardial infarction was J‐shaped in men, whereas it increased linearly with higher LDL‐C in women. In both sexes, the association between stroke mortality and LDL‐C was not significant.

Conclusion: This study adds to the uncertainty of the role of elevated levels of LDL‐C as a risk factor for mortality in old people.
Obesity among individuals with serious mental illness
Authors: Dickerson F. B. , Brown C. H. , Kreyenbuhl J. A. , Fang L. , Goldberg R. W. , Wohlheiter K. , Dixon L. B.
Published: October 2005

Objective:  To study the distribution and correlates of body mass index (BMI) among individuals with serious mental illness.

Method:  A total of 169 participants were recruited from randomly selected out‐patients receiving community‐based psychiatric care and were interviewed with items from the National Health and Nutrition Examination Survey (NHANES) III. Their BMI was compared with that of 2404 matched individuals from the NHANES data set.

Results:  The distribution of BMI in the psychiatric sample significantly differed from that of the comparison group; 50% of women and 41% of men were obese compared with 27% and 20% in the comparison group. Within the psychiatric sample, higher BMI was associated with current hypertension and diabetes, a wish to weigh less, and reduced health‐related functioning.

Conclusion:  Obesity is more prevalent among individuals with serious mental illness than in demographically matched individuals from the US general population. Among persons with mental illness, obesity is associated with co‐occurring health problems.
Reducing the duration of untreated first‐episode psychosis – effects on baseline social functioning and quality of life
Authors: Melle I. , Haahr U. , Friis S. , Hustoft K. , Johannessen J. O. , Larsen T. K. , Opjordsmoen S. , Rund B. R. , Simonsen E. , Vaglum P. , McGlashan T.
Published: October 2005

Objective:  Long duration of untreated psychosis (DUP) is associated with poorer outcome. The TIPS study demonstrated that DUP can be reduced through early detection (ED). As quality of life (QoL) is associated with DUP it is expected that reduction of DUP leads to better QoL.

Method:  Consecutive first‐episode patients with a DSM‐IV diagnosis of non‐organic, non‐affective psychosis were included, 281 patients gave informed consent and 263 completed a full evaluation of QoL.

Results:  There were no differences in subjective QoL between ED and No‐ED groups attributable to reduction in DUP. There were significant bivariate differences in frequency of family and social contacts in favor of the ED group, but multivariate analyses indicated that these differences were based on differences in sample characteristics.

Conclusion:  Deterioration in QoL may precede overt symptom formation. Focus on functional loss in ED educational campaigns may identify risk subjects earlier in the course of the disorder.
Effect of the menstrual cycle on pain experience associated with periodontal therapy
Authors: Özçaka Özgün , Bıçakçı Nurgün , Köse Timur
Published: October 2005

Objectives: The aim of this pilot cross‐over study was to compare preliminarily the pain perception of female patients undergoing periodontal debridement during menstrual or pre‐menstrual phases (peri‐menstrual period) with that observed during mid‐menstrual phase (post‐menstrual period).

Materials and Methods: Twenty women with moderate‐to‐advanced chronic periodontitis and regular menstrual cycles were asked to complete Corah's Dental Anxiety Scale (DAS) during the first debridement visit. Patients were randomly assigned to receive their first debridement visit during either their peri‐menstrual or post‐menstrual period. Debridement was performed in bilateral quadrants of patients during the periods. Pain levels for each quadrant were asssessed with a Visual Analogue Scale (VAS), after each debridment visit.

Results: There was no significant correlation of order of treatment in the intensity of perceived pain during the periods (p<0.05). The median VAS scores were 22.0 and 15.2 mm in the peri‐menstrual and the post‐menstrual period, respectively. Increase in pain perception among females during their peri‐menstrual period was significantly greater than their post‐menstrual period (p<0.05).

Conclusion: No clinical conclusions can be drawn at this stage as this pilot study did not have a sufficiently broad population to generalize these observations to all female periodontal patients. Providing clinicians with information about patients' menstrual cycle during debridement can alter the pain experience.
The crossover design to evaluate the efficacy of plaque removal in tooth‐brushing studies
Authors: McCracken G. I. , Steen N. , Preshaw P. M. , Heasman L. , Stacey F. , Heasman P. A.
Published: October 2005

Objectives: To evaluate the crossover clinical trial design to assess plaque removal efficacy of the Sonicare Elite.

Material and Methods: A single‐cohort, 12‐week, two‐treatment, single‐blind, crossover clinical trial recruited 45 subjects. Plaque was recorded using the modified Quigley and Hein index plaque index (PI). After screening, subjects used the toothbrush for 2 weeks and were reminded to abstain from tooth cleaning 12–18 h prior to appointments. At visit two, subjects were randomized to 2 or 2½ min. brushing time. PIs was recorded pre‐ and post‐brushing. Subjects brushed for the allocated time for a further 2 weeks. At visit 3, PIs were recorded pre‐ and post‐brushing. Two weeks later, at visit 4, the subjects crossed over and the protocol was repeated.

Results: There was no evidence of a learning effect within each arm of the crossover. A significant period effect was detected; however, no significant treatment by period effect was found. 2½ min. brushing removed more plaque at full mouth (p=0.037), smooth (p=0.012) and lingual (p=0.002) sites compared with 2 min.

Conclusion: The crossover design is a valid model for assessing plaque removal efficacy in tooth‐brushing studies where no carry‐over effect is clinically plausible.
Bone response to different strength orthodontic forces in animals with periodontitis
Authors: Garat J. A. , Gordillo M. E. , Ubios A. M.
Published: October 2005

Background:  Occlusal alterations resulting from tooth movements caused by periodontitis‐related bone loss are often corrected with orthodontic treatments. Although the outcome is usually satisfactory, a quantitative histomorphometric study of bone response would contribute to improving treatment planning and optimizing results.

Methods and Results:  This study is a histomorphometric analysis of alveolar bone response to 51 and 75‐g orthodontic forces applied to rat molars subjected to experimental periodontitis by placing a ligature around the neck of the molar during 48 h. The orthodontic device consisted of two bands with a tube welded to their palatine aspect, through which the arms of a helicoidal spring were threaded so as to exert force toward palatine. The device was placed immediately and 48 h after removing the ligatures. When applied 48 h post‐removal of the ligature, both orthodontic forces caused an increase in bone volume in the periodontitis group.

Conclusions:  Our study shows that application of orthodontic forces once periodontal infection has been controlled contributes to increasing alveolar bone volume, consequently improving bone quality.
Nonclassical PITPs Activate PLD via the Stt4p PtdIns‐4‐kinase and Modulate Function of Late Stages of Exocytosis in Vegetative Yeast
Authors: Routt Sheri M. , Ryan Margaret M. , Tyeryar Kimberly , Rizzieri Kellie E. , Mousley Carl , Roumanie Olivier , Brennwald Patrick J. , Bankaitis Vytas A.
Published: October 2005

Phospholipase D (PLD) is a PtdCho‐hydrolyzing enzyme that plays central signaling functions in eukaryotic cells. We previously demonstrated that action of a set of four nonclassical and membrane‐associated Sec14p‐like phosphatidylinositol transfer proteins (PITPs) is required for optimal activation of yeast PLD in vegetative cells. Herein, we focus on mechanisms of Sfh2p and Sfh5p function in this regulatory circuit. We describe several independent lines of in vivo evidence to indicate these SFH PITPs regulate PLD by stimulating PtdIns‐4,5‐P2 synthesis and that this stimulated PtdIns‐4,5‐P2 synthesis couples to action of the Stt4p PtdIns 4‐kinase. Furthermore, we provide genetic evidence to suggest that specific subunits of the yeast exocyst complex (i.e. a component of the plasma membrane vesicle docking machinery) and the Sec9p plasma membrane t‐SNARE are regulated by PtdIns(4,5)P2 and that Sfh5p helps regulate this interface in vivo. The collective in vivo and biochemical data suggest SFH‐mediated stimulation of Stt4p activity is indirect, most likely via a substrate delivery mechanism.
Oral Hygiene and dental student's knowledge, attitude and behaviour in managing HIV/AIDS patients
Authors: Erasmus S , Luiters S , Brijlal P
Published: October 2005

Abstract:  The human immunodeficiency virus (AIDS) and the acquired immunodeficiency syndrome (AIDS) have profoundly affected every aspect of the public health sector. The possibility of HIV transmission in the oral health care setting is very rare. Nonetheless, the oral health care environment has become a helpful setting for early detection, as most lesions of HIV infection present orally during the first stages of the disease. Willingness to treat patients with HIV/AIDS appears to be related to knowledge of the disease process, its oral manifestations and modes of transmission, thus influencing health workers’ attitudes and behaviour towards management of HIV/AIDS patients. This study assessed the level of management of HIV/AIDS patients amongst dental and oral hygiene students at the University of the Western Cape Dental faculty. Student's knowledge of HIV/AIDS, their behaviour and attitude in treating HIV/AIDS patients, the precautionary measures practiced and their perceptions of curriculum preparation on HIV/AIDS were assessed. Data were collected by means of a self‐ administered questionnaire. The results indicated that students’ knowledge on HIV/AIDS generally increased as they progressed throughout their curriculum but their utilization of all barrier techniques for infection control and clinical protocol, lacked consistency and compliance. Given the fact that the possibility of transmission of HIV/AIDS does exist within the dental setting, it is important that supervisors reinforce universal precautions. Clinical application of these precautions has a direct impact on the spread of the disease.
Dysphagia management in a 3‐year dental hygiene education programme in Japan
Authors: Sato Yoko , Miura Ai , Saito Atsushi
Published: October 2005

Abstract:  This paper reports the development and evaluation of a dysphagia management course taught to the third year dental hygiene students during 2004–2005 as one framework of the new curriculum. The course consisted of lectures by specialists in each field, basic practice and clinical practice at a facility for the elderly. Evaluation of the course showed that improvements were found in students’ understanding in certain subjects when compared with that during 2003–2004. Scores on the post‐test were statistically significantly higher than those on the pre‐test, showing that basic knowledge of the students had been improved. Introductory and follow‐up lectures by dental hygiene instructors and appropriate basic practice enhanced the learning process of the students. In the clinical practice, the concept of ‘dental hygiene process of care’ was incorporated. The dental hygiene process facilitated the students in planning and implementing dental hygiene care that meets the needs of the individual clients. This active learning experience enhanced the students’ understanding of dysphagia management. Although further improvements are necessary, this dysphagia management course should help dental hygienists in playing a greater role in the field of oral care and dysphagia rehabilitation.
In vitro gamma‐secretase cleavage of the Alzheimer's amyloid precursor protein correlates to a subset of presenilin complexes and is inhibited by zinc
Authors: Hoke David E. , Tan Jiang‐Li , Ilaya Nancy T. , Culvenor Janetta G. , Smith Stephanie J. , White Anthony R. , Masters Colin L. , Evin Geneviève M.
Published: October 2005

The γ‐secretase complex mediates the final proteolytic event in Alzheimer's disease amyloid‐β biogenesis. This membrane complex of presenilin, anterior pharynx defective, nicastrin, and presenilin enhancer‐2 cleaves the C‐terminal 99‐amino acid fragment of the amyloid precursor protein intramembranously at γ‐sites to form C‐terminally heterogeneous amyloid‐β and cleaves at an ε‐site to release the intracellular domain or ε‐C‐terminal fragment. In this work, two novel in vitroγ‐secretase assays are developed to further explore the biochemical characteristics of γ‐secretase activity. During development of a bacterial expression system for a substrate based on the amyloid precursor protein C‐terminal 99‐amino acid sequence, fragments similar to amyloid‐β and an ε‐C‐terminal fragment were observed. Upon purification this substrate was used in parallel with a transfected source of substrate to measure γ‐secretase activity from detergent extracted membranes. With these systems, it was determined that recovery of size‐fractionated cellular and tissue‐derived γ‐secretase activity is dependent upon detergent concentration and that activity correlates to a subset of high molecular mass presenilin complexes. We also show that by changing the solvent environment with dimethyl sulfoxide, detection of ε‐C‐terminal fragments can be elevated. Lastly, we show that zinc causes an increase in the apparent molecular mass of an amyloid precursor protein γ‐secretase substrate and inhibits its cleavage. These studies further refine our knowledge of the complexes and biochemical factors needed for γ‐secretase activity and suggest a mechanism by which zinc dysregulation may contribute to Alzheimer's disease pathogenesis.
Atrial natriuretic peptide‐dependent photolabeling of a regulatory ATP‐binding site on the natriuretic peptide receptor‐A
Authors: Joubert Simon , Jossart Christian , McNicoll Normand , De Léan André
Published: October 2005

The natriuretic peptide receptor‐A (NPR‐A) is composed of an extracellular ligand‐binding domain, a transmembrane‐spanning domain, a kinase homology domain (KHD) and a guanylyl cyclase domain. Because the presence of ATP or adenylylimidodiphosphate reduces atrial natriuretic peptide (ANP) binding and is required for maximal guanylyl cyclase activity, a direct interaction of ATP with the receptor KHD domain is plausible. Therefore, we investigated whether ATP interacts directly with a binding site on the receptor by analyzing the binding of a photoaffinity analog of ATP to membranes from human embryonic kidney 293 cells expressing the NPR‐A receptor lacking the guanylyl cyclase moiety (ΔGC). We demonstrate that this receptor (NPR‐A‐ΔGC) can be directly labeled by 8‐azido‐3′‐biotinyl‐ATP and that labeling is highly increased following ANP treatment. The mutant receptor ΔKC, which does not contain the KHD, is not labeled. Photoaffinity labeling of the NPR‐A‐ΔGC is reduced by 50% in the presence of 550 µm ATP, and competition curve fitting studies indicate a Hill slope of 2.2, suggestive of cooperative binding. This approach demonstrates directly that the interaction of ANP with its receptor modulates the binding of ATP to the KHD, probably through a conformational change in the KHD. In turn, this conformational change is essential for maximal activity. In addition, the ATP analog, 8‐azido‐adenylylimidodiphosphate, inhibits guanylyl cyclase activity but increases ANP binding to the extracellular domain. These results suggest that the KHD regulates ANP binding and guanylyl cyclase activity independently.
Biochemical characterization of human umbilical vein endothelial cell membrane bound acetylcholinesterase
Authors: Carvalho Filomena A. , Graça Luís M. , Martins‐Silva João , Saldanha Carlota
Published: October 2005

Acetylcholinesterase is an enzyme whose best‐known function is to hydrolyze the neurotransmitter acetylcholine. Acetylcholinesterase is expressed in several noncholinergic tissues. Accordingly, we report for the first time the identification of acetylcholinesterase in human umbilical cord vein endothelial cells. Here we further performed an electrophoretic and biochemical characterization of this enzyme, using protein extracts obtained by solubilization of human endothelial cell membranes with Triton X‐100. These extracts were analyzed under polyacrylamide gel electrophoresis in the presence of Triton X‐100 and under nondenaturing conditions, followed by specific staining for cholinesterase or acetylcholinesterase activity. The gels revealed one enzymatically active acetylcholinesterase band in the extracts that disappeared when staining was performed in the presence of eserine (an acetylcholinesterase inhibitor). Performing western blotting with the C‐terminal anti‐acetylcholinesterase IgG, we identified a single protein band of approximately 70 kDa, the molecular mass characteristic of the human monomeric form of acetylcholinesterase. The western blotting with the N‐terminal anti‐acetylcholinesterase IgG antibody revealed a double band around 66–70 kDa. Using the Ellman's method to measure the cholinesterase activity in human umbilical vein endothelial cells, regarding its substrate specificity, we confirmed the existence of an acetylcholinesterase enzyme. Our studies revealed a predominance of acetylcholinesterase over other cholinesterases in human endothelial cells. In conclusion, we have demonstrated the existence of a membrane‐bound acetylcholinesterase in human endothelial cells. In future studies, we will investigate the role of this protein in the endothelial vascular system.
Secretion of the mammalian Sec14p‐like phosphoinositide‐binding p45 protein
Authors: Merkulova Maria , Huynh Huong , Radchenko Vitaly , Saito Kan , Lipkin Valery , Shuvaeva Tatiana , Mustelin Tomas
Published: October 2005

Protein–lipid interactions are important for protein targeting, signal transduction, lipid transport, and the maintenance of cellular compartments and membranes. Specific lipid‐binding protein domains, such as PH, FYVE, PX, PHD, C2 and SEC14 homology domains, mediate interactions between proteins and specific phospholipids. We recently cloned a 45‐kDa protein from rat olfactory epithelium, which is homologous to the yeast Sec14p phosphatidylinositol (PtdIns) transfer protein and we report here that this protein binds to PtdIns(3,4,5)P3and far weaker to less phosphorylated derivatives of PtdIns. Expression of the p45 protein in COS‐1 cells resulted in accumulation of the protein in secretory vesicles and in the extracellular space. The secreted material contained PtdIns(3,4,5)P3. Our findings are the first report of a Sec14p‐like protein involved in transport out of a cell and, to the best of our knowledge, inositol‐containing phospholipids have not previously been detected in the extracellular space. Our findings suggest that p45 and phosphoinositides may participate in the formation of the protective mucus on nasal epithelium.
The Sexual Interest and Desire Inventory—Female (SIDI-F): Item Response Analyses of Data from Women Diagnosed with Hypoactive Sexual Desire Disorder
Authors: Sills Terrence , Wunderlich Glen , Pyke Robert , Segraves R. Taylor , Leiblum Sandra , Clayton Anita , Cotton Dan , Evans Kenneth
Published: October 2005

Introduction

Hypoactive sexual desire disorder (HSDD) is the most common sexual complaint in women. Currently there are no validated instruments for specifically assessing HSDD severity, or change in HSDD severity in response to treatment, in premenopausal women. The Sexual Interest and Desire Inventory—Female (SIDI-F) is a clinician-administered instrument that was developed to measure severity and change in response to treatment of HSDD. Seventeen items were included in a preliminary version of the SIDI-F, including 10 items related to desire, and seven items related to possible comorbid factors (e.g., other kinds of sexual dysfunction, general relationship satisfaction, mood, and fatigue).

Aim

The aim of the study was to use the outcome of item response analyses of blinded data from two randomized, placebo-controlled trials, to assist in the revision of the scale.

Methods

A nonparametric item response (IRT) model was used to assess the relation between item functioning and HSDD severity on this preliminary version of the SIDI-F.

Results

Results show that the majority of SIDI-F items demonstrated good sensitivity to differences in overall HSDD severity. That is, there was an orderly relation between differences in option selection for an item and differences in overall HSDD severity. The IRT analyses further indicated that revisions were warranted for a number of these items. Five items were not sensitive to differences in HSDD severity and were removed from the scale.

Conclusion

The SIDI-F is a brief, clinician-administered rating scale designed to assess severity of HSDD symptoms in women. IRT analyses show that majority of the items of the SIDI-F function well in discriminating individual differences in HSDD severity. A revised 13-item version of the SIDI-F is currently undergoing further validation.
Sexual Dysfunction in Female Partners of Men Who Have Undergone Radical Prostatectomy Correlates with Sexual Dysfunction of the Male Partner
Authors: Shindel Alan , Quayle Sejal , Yan Yan , Husain Adnan , Naughton Cathy
Published: October 2005

Introduction

Preservation and restoration of erectile function after radical prostatectomy (RP) for prostate cancer has been extensively studied. However, the influence of RP on the sexual function of female partners is poorly understood.

Aim

The purpose of this retrospective study is to assess sexuality in men who have undergone RP for prostate cancer and their female partners.

Methods

Men who underwent RP for localized prostate cancer at our institution from 1996 to 2000 were identified and invited to participate in this study with their female partners. Both partners completed a demographic survey. Men completed the International Index of Erectile Function (IIEF) and female partners completed the Female Sexual Function Index (FSFI) and supplemental questions.

Main Outcome Measures

Correlation between IIEF and FSFI domain scores was determined in matched couples using Pearson correlation coefficient. Kappa statistics and Spearman correlation coefficient were calculated for supplemental questions and IIEF domain scores.

Results

Of 1,134 men contacted by letter, 90 (8%) couples completed demographic surveys and both the IIEF/FSFI. Pearson correlation coefficients of IIEF and FSFI domain scores in matched couples demonstrated significant correlation (P < 0.05) of all IIEF domains with all FSFI domains with the exception of male erectile function and overall sexual function with female sexual desire. There was moderate agreement between partner supplemental questions and IIEF domain scores.

Conclusions

Response rate was very low. FSFI domain scores correlate with IIEF domain scores, indicating an interrelationship between male and female sexual dysfunction in these couples. Evaluation and treatment of sexual dysfunction after RP should involve both partners.
Extracts from Tephrosia vogelii for the protection of stored legume seeds against damage by three bruchid species
Authors: Koona P. , Dorn S.
Published: October 2005

Aliquots of powdered dried leaves of Tephrosia vogelii (Leguminosae – Papilionoideae) were extracted with hexane, acetone and ethanol. The extracts were tested for their potential to protect stored legume seeds from damage by the bruchids Acanthoscelides obtectus, Callosobruchus maculatus and Callosobruchus chinensis (Coleoptera – Bruchidae). While the acetone and ethanol extracts were ineffective except for a significant but low effect on A. obtectus, the hexane extract had a relatively high efficacy, providing similar control of all three bruchid species. This effect was manifested in slowly‐reduced adult survival within 7 days and in reduced numbers of eggs laid and of F1 progeny produced, resulting in seed damage averaging 7.1% compared to 99.8% in the untreated controls after one generation. These findings are discussed in the context of previously identified constituents of T. vogelii, the rotenoids rotenone, tephrosin and deguelin.
Coccidioidal meningitis presenting as memory loss
Authors: Hoffman Snyder Charlene
Published: October 2005

Purpose

This case study is designed to help the nurse practitioner recognize atypical symptoms of coccidioidal meningitis, particularly in high‐risk groups that require further diagnostic treatment.

Data sources

Selected research, clinical articles, and case studies.

Conclusions

Coccidioidal meningitis is a potentially lethal infection unless recognized and treated. Unlike other infectious meningitides that present with more acute meningeal symptoms, disseminated coccidioidomycosis can present insidiously. When it presents as cognitive dysfunction, it may be mistaken for early dementia and if undiagnosed can result in death. While it is an infectious disease that is endemic to a small number of southwestern states, these areas see a high volume of tourists who can unwittingly become infected. Knowledge of this infectious disease and the many ways it can imitate other diseases is critical to its early recognition and treatment.

Implications for practice

Failure to recognize this reemerging, endemic fungal infection in high‐risk groups can result in death.
Fetal alcohol spectrum disorders prevention: An exploratory study of women's use of, attitudes toward, and knowledge about alcohol
Authors: Walker Deborah S. , Darling Fisher Cynthia S. , Sherman Anita , Wybrecht Barbara , Kyndely Kathleen
Published: October 2005

Purpose

The incidence of fetal alcohol spectrum disorders (FASD) is increasing, even though it is 100% preventable. This study examined use of, knowledge about, and attitudes toward alcohol of women requesting emergency contraception (EC) and/or a pregnancy test, and evaluated whether a brief intervention would be effective in educating them about the risks of FASD.

Data sources

Fifty women from two outpatient clinics participated. Information was collected on demographic and personal health habits, alcohol use, and knowledge of and attitudes toward alcohol. As a brief intervention to increase knowledge about FASD, participants read a short pamphlet about the risks of alcohol exposure in pregnancy and then completed a post‐test questionnaire. Descriptive statistics, including means, standard deviations, and skewness, were calculated for all variables. Pearson correlations were computed to assess relationships between demographic/lifestyle variables and attitudes toward and knowledge about alcohol. Paired t‐tests were used to analyze the relationship between pretest and post‐test knowledge scores.

Conclusions

The majority of participants were single (76%), college educated (94%), and received EC at the clinic visit (60%). The average age was 24 years. Slightly over half (52%) reported drinking beer at least once a week, with one to six cans on occasion. Younger women expressed more tolerant attitudes toward alcohol use (p= .02) and drank significantly more beer on occasion (p= .015). Women who reported drinking alcohol when they last had sex were significantly (p= .017) less tolerant in their attitudes toward alcohol use. The intervention used in this study was effective in communicating knowledge about FASD to this population (p < .0001).

Implications for practice

These findings suggest that young women may be engaging in behaviors that could put potential offspring at risk for exposure to alcohol. Clinicians are advised to take a thorough history to determine alcohol use in all women of childbearing age and to provide information regarding FASD prevention.
Delays of stimulus-frequency otoacoustic emissions and cochlear vibrations contradict the theory of coherent reflection filtering
Authors: Siegel Jonathan H. , Cerka Amanda J. , Recio-Spinoso Alberto , Temchin Andrei N. , van Dijk Pim , Ruggero Mario A.
Published: October 2005

When stimulated by tones, the ear appears to emit tones of its own, stimulus-frequency otoacoustic emissions (SFOAEs). SFOAEs were measured in 17 chinchillas and their group delays were compared with a place map of basilar-membrane vibration group delays measured at the characteristic frequency. The map is based on Wiener-kernel analysis of responses to noise of auditory-nerve fibers corroborated by measurements of vibrations at several basilar-membrane sites. SFOAE group delays were similar to, or shorter than, basilar-membrane group delays for frequencies >4kHz and <4kHz, respectively. Such short delays contradict the generally accepted “theory of coherent reflection filtering” [Zweig and Shera, J. Acoust. Soc. Am. 98, 2018–2047 (1995)], which predicts that the group delays of SFOAEs evoked by low-level tones approximately equal twice the basilar-membrane group delays. The results for frequencies higher than 4kHz are compatible with hypotheses of SFOAE propagation to the stapes via acoustic waves or fluid coupling, or via reverse basilar membrane traveling waves with speeds corresponding to the signal-front delays, rather than the group delays, of the forward waves. The results for frequencies lower than 4kHz cannot be explained by hypotheses based on waves propagating to and from their characteristic places in the cochlea.
Comparison of nonlinear dynamic methods and perturbation methods for voice analysis
Authors: Zhang Yu , Jiang Jack J. , Wallace Stephanie M. , Zhou Liang
Published: October 2005

Nonlinear dynamic methods and perturbation methods are compared in terms of the effects of signal length, sampling rate, and noise. Results of theoretical and experimental studies quantitatively show that measurements representing frequency and amplitude perturbations are not applicable to chaotic signals because of difficulties in pitch tracking and sensitivity to initial state differences. Perturbation analyses are only reliable when applied to nearly periodic voice samples of sufficiently long signal lengths that were obtained at high sampling rates and low noise levels. In contrast, nonlinear dynamic methods, such as correlation dimension, allow the quantification of chaotic time series. Additionally, the correlation dimension method presents a more stable analysis of nearly periodic voice samples for shorter signal lengths, lower sampling rates, and higher noise levels. The correlation dimension method avoids some of the methodological issues associated with perturbation methods, and may potentially improve the ability for real time analysis as well as reduce costs in experimental designs for objectively assessing voice disorders.
Correcting echo-integration data for transducer motion
Authors: Dunford Adam J.
Published: October 2005

When calculating biomass estimates using acoustic echo-integration it is necessary to account for the change in pointing direction of the transducer between transmission and reception. It is shown that a single correction function can be obtained for a wide range of circular transducers, thus removing the need for the correction to be recalculated for each individual transducer. This correction function is also applicable to those transducers whose beam pattern approximates that of a circular transducer.
Propagation of Lamb waves in a plate with a periodic grating: Interpretation by phonon
Authors: Leduc Damien , Hladky Anne-Christine , Morvan Bruno , Izbicki Jean-Louis , Pareige Pascal
Published: October 2005

In this paper the propagation of Lamb waves in an aluminium plate with a periodic grating containing triangular grooves is studied. Numerical simulations (FEM) are performed. A single incident mode is excited on a flat area and the interaction with the periodic grating is studied. Reflected converted waves are observed when the incident Lamb wave passes through the grating. At the entrance of the periodic grating, a phonon relation is written between the incident signal, the converted mode, and the phonon related to the grating. An experimental verification of the phonon relation is carried out.
Finding intonational boundaries using acoustic cues related to the voice source
Authors: Choi Jeung-Yoon , Hasegawa-Johnson Mark , Cole Jennifer
Published: October 2005

Acoustic cues related to the voice source, including harmonic structure and spectral tilt, were examined for relevance to prosodic boundary detection. The measurements considered here comprise five categories: duration, pitch, harmonic structure, spectral tilt, and amplitude. Distributions of the measurements and statistical analysis show that the measurements may be used to differentiate between prosodic categories. Detection experiments on the Boston University Radio Speech Corpus show equal error detection rates around 70% for accent and boundary detection, using only the acoustic measurements described, without any lexical or syntactic information. Further investigation of the detection results shows that duration and amplitude measurements, and, to a lesser degree, pitch measurements, are useful for detecting accents, while all voice source measurements except pitch measurements are useful for boundary detection.