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PubMed1993

Asymmetry of orientation and voltage gating of the Acidovorax delafieldii porin Omp34 in lipid bilayers.

The functional properties of the major outer-membrane protein of Acidovorax delafieldii, the anion-selective porin Omp34, were investigated in artificial membranes. Detergent-solubilized porin incorporates into the membrane in a undirectional orientation solely determined by protein features. This enabled us to characterize the vectorial properties of the porin channels. Omp34 is electrostatically asymmetric regarding both the ion conductivity of a single trimer and the macroscopic ion conductance of multiple porin molecules. Voltage-dependent closing occurred at negative potentials; 50% of the channels were already closed at -10 mV (switching voltage). Our experimental results suggest that protein charges situated on flexible parts inside the channel are involved in the gating mechanism. A simple model is proposed illustrating the mechanism of voltage-dependent opening and closing of the porin channels. This model explains the functional characteristics of Omp34 and the dependence of the switching voltage on the electrolyte concentration in particular. Further factors influencing voltage gating include the buffer concentration as well as the technique used for membrane formation. Altogether these factors may explain the relatively high voltages needed to obtain voltage gating with other porins.

Bacterial Outer Membrane Proteins↗

PubMed1998

Complex motion stimuli localize higher-order visual processing in normal observers and in patients with parietal lesions.

The present paper illustrates how modern techniques applied in neuroscience can help us to understand the processing of visual information in the human brain and, in turn, how they can be helpful to characterize functional deficits in patients with cortical lesions. Based on theoretical considerations, motion stimuli are developed that require very specific operations to be performed by the visual system. Computational models explaining the processing of these 'Fourier' and 'second-order' motion stimuli are characterized by increasing complexity. The same types of stimuli are used to map the distribution of cortical activity during motion perception by measuring the magnetic and electrical fields on the head surface. Clinical investigations of patients with lesions in the parietal cortex indicate specific deficits in the perception of such stimuli that can be related to the lesion sites.

Action Potentials↗

PubMed2005

Medical students' perceptions of the elements of effective inpatient teaching by attending physicians and housestaff.

BACKGROUND: Most studies of effective inpatient teaching have focused on teaching by attending physicians. OBJECTIVE: To identify and compare medical students' perceptions of behaviors associated with teaching effectiveness of attending physicians and housestaff (residents and interns). DESIGN AND PARTICIPANTS: Third-year students who spent 4 weeks on a general internal medicine inpatient service during academic year 2003-2004 completed surveys using a 5-point Likert-type scale. Students evaluated numerous teaching behaviors of attendings and housestaff and then evaluated their overall teaching effectiveness. MEASUREMENTS: Each behavior was correlated with the perceived teaching effectiveness in univariate and regression analyses. RESULTS: Seventy-two students were taught by 23 attendings and 73 housestaff. Of 144 possible teaching evaluations, they completed 142 (98.6%) for attendings and 128 (88.9%) for housestaff. The mean rating for perceived teaching effectiveness was 4.48 (SD 0.82) for attendings and 4.39 (SD 0.80) for housestaff. For attending physicians, teaching effectiveness correlated most strongly with enthusiasm for teaching (R(2)=63.6%) but was also associated with inspiring confidence in knowledge and skills, providing feedback, and encouraging students to accept increasing responsibility. Housestaff teaching effectiveness correlated most strongly with providing a role model (R(2)=61.8%) but was also associated with being available to students, performing effective patient education, inspiring confidence in knowledge and skills, and showing enthusiasm for teaching. Regression models explained 79.7% and 73.6% of the variance in evaluations of attendings and housestaff, respectively. CONCLUSIONS: Students' perceptions of effective teaching behaviors differ for attending physicians and housestaff, possibly reflecting differences in teaching roles or methods.

Attitude of Health Personnel↗

PubMed1995

Sinus headaches reconsidered: referred cephalgia of rhinologic origin masquerading as refractory primary headaches.

Headache associated with acute sinusitis is a well-recognized entity; the diagnosis is easily made due to the associated nasal and sinus symptoms. However, the phenomenon of referred headache from chronic sinusitis or intranasal abnormalities or both without upper respiratory symptoms is not well understood. Only recently have the nasal and sinus cavities been adequately visualized by both the human eye and radiographic techniques; a fact that may account for the historic neglect in considering this region a factor in headache etiology. Modern techniques employed in the workup of sinusitis, namely the use of rigid nasal endoscopes and coronal-plane CT scanning, have greatly enhanced the clinician's ability to evaluate and diagnose pathology in this area. This report describes a series of patients presenting with various primary headache syndromes without significant nasal or sinus symptoms who failed to respond to conventional antiheadache therapy. On nasal endoscopic and coronal CT examinations, various intranasal and sinus abnormalities were found (either anatomic variations or subclinical inflammation). Medical and/or surgical therapy addressing the sinonasal pathology resulted in improvement in every case, ranging from decreased severity of attacks to total resolution of headaches. A model explaining the possible mechanism of referred vascular-type headache from sinus and nasal origin is proposed.

Adolescent↗

PubMedDate not supplied

Valproate competes with palmitate for binding to serum albumin.

Addition of sodium valproate (VPA) to a buffered solution of human serum albumin (HSA) or to serum reduces binding affinity for palmitate. A maximal pharmacologic VPA concentration, 700 microM, added to a 300-microM albumin solution, reduces the reserve albumin concentration for binding of palmitate by a factor of 0.64. One possible site model explaining these findings may be that VPA competes strongly with one among three palmitate molecules, bound to albumin with high affinity, and induces a weaker displacement of a second palmitate.

Binding, Competitive↗

PubMed2005

Understanding atrial symptom reports: objective versus subjective predictors.

BACKGROUND: Atrial fibrillation (AF) is the most common cardiac arrhythmia and is associated with a variety of symptoms such as dizziness, palpitations, shortness of breath, and other signs of heart failure, which in turn impact quality of life (QOL). Implantable cardioverter defibrillators with atrial therapies (ICDs-ATs) have been shown to reduce AF symptoms and improve QOL in select AF samples. METHOD: This study examined the strength of relationships between objective (device-detected AF events) versus subjective (emotional symptoms) data and AF symptoms (number) reported as part of the Patient Atrial Shock Survey of Acceptance and Tolerance Study (N = 96, 72% men, M age = 65, SD = 12). Depression and anxiety were assessed via the Center for Epidemiological Studies--Depression Scale and the-State Trait Anxiety Inventory. AF disease burden was measured via a number of device-detected AF episodes and the Atrial Tachyarrhythmia Symptom Severity Scale. RESULTS: Hierarchical multiple regression analysis indicated that negative emotions accounted for a significant 13.2% of unique variance in AF symptom score (F change (1, 54) = 9.625, P = 0.003). On the other hand, the number of device-detected AF episodes accounted for non-significant 8.2% of unique variance in the AF symptom score (P = 0.167). The full model explained 25.7% of the variance in AF symptom score (F(6, 54) = 3.110, P = 0.011). Specifically, greater number of treated AF episodes (beta= 0.251, P = 0.043) and higher levels of negative emotions (beta= 0.369, P = 0.003) predicted greater number of reported AF symptoms. CONCLUSION: Therefore, psychological distress may be a significant confounding factor affecting patient's report of AF symptoms rather than the actual experience of recurrent AF episodes.

Aged↗

PubMed2004

Measuring patient-level clinical outcomes of home health care.

PURPOSE: To examine the use of the Outcomes Assessment and Information Set (OASIS) data to analyze patient-level outcomes of home health care. DESIGN: OASIS data were obtained on 1,015 patients who received home health care services for 60 days or fewer from a large, independent home health agency between August 1998 and December 1999. METHODS: An index was constructed consisting of 16 OASIS measures, primarily activities of daily living (ADL) and instrumental activities of daily living (IADL). Scores were computed for functional status on admission and at discharge. Predictors of functional status at discharge were identified by regression analysis. FINDINGS: 78.1% of patients improved, 18.5% declined, and 2.8% showed no change. The model explained 57.2% of variance in functional status at discharge. Age, visual impairment, having Medicaid as a payer, urinary incontinence, cognitive impairment, and use of unplanned or emergency care were negatively associated with functional outcomes of care. Being treated for open wounds or lesions, cardiovascular and orthopedic conditions were positively associated with functional outcomes. CONCLUSIONS: OASIS data can be used to analyze patient-level functional outcomes of short-term home health services. Further research is needed to continue refining methods of analyzing patient outcomes and their predictors.

Activities of Daily Living↗

PubMedDate not supplied

Malaria sporozoites release circumsporozoite protein from their apical end and translocate it along their surface.

Plasmodium sporozoites, the causative agents of malaria, release circumsporozoite (CS) protein into medium when under conditions simulating those that the parasites encounter in the bloodstream of the vertebrate host. CS protein of the rodent parasite, Plasmodium berghei, is released as the lower molecular weight form, Pb44. This release is substratum- and antibody-independent. Previous studies show that CS protein is released at the trailing, posterior end of motile sporozoites. Video and electron microscopic studies now demonstrate that CS protein is released at the apical end of cytochalasin b-immobilized sporozoites. We propose that CS protein released from the apical end, the leading end of gliding sporozoites, adheres to the sporozoite surface and is translocated posteriorly by a cytochalasin-sensitive and apparently actin-mediated surface motor, which drives gliding motility. This model explains the mechanism of both the circumsporozoite precipitation (CSP) reaction and formation of the CS protein trail by gliding sporozoites.

Animals↗

PubMed2000

Metabolism of ricinoleic acid into gamma-decalactone: beta-oxidation and long chain acyl intermediates of ricinoleic acid in the genus Sporidiobolus sp.

In order to study differences in gamma-decalactone production in yeast, four species of Sporidiobolus were cultivated with 5% of methyl ricinoleate as the lactone substrate. In vivo studies showed different time courses of intermediates of ricinoleic acid breakdown between the four species. In vitro studies of the beta-oxidation system were conducted with crude cell extracts of Sporidiobolus spp. and with ricinoleyl-CoA (RCoA) as substrate. The beta-oxidation was detected by measuring acyl-CoA oxidase, 3-hydroxyacyl-CoA dehydrogenase activities, and acetyl-CoA production. The time courses of the CoA esters resulting from RCoA breakdown by crude extract of Sporidiobolus spp. permit the proposal of different metabolic models in the yeast. These models explained the differences observed during in vivo studies.

Acylation↗

PubMed2004

Bone level change at implant-supported fixed partial dentures with and without cantilever extension after 5 years in function.

OBJECTIVE: The aim of this study was to retrospectively analyze whether the inclusion of cantilever extensions increased the amount of marginal bone loss at free-standing, implant-supported, fixed partial dentures (FPDs) over a 5-year period of functional loading. MATERIAL AND METHODS: The patient material comprised 45 periodontally treated, partially dentate patients with a total of 50 free-standing FPDs supported by implants of the Astra Tech System. Following FPD placement (baseline) the patients were enrolled in an individually designed supportive care program. A set of criteria was collected at baseline to characterize the FPDs. The primary outcome variable was change in peri-implant bone level from the time of FPD placement to the 5-year follow-up examination. The comparison between FPDs with and without cantilevers was performed at three levels: FPD level, implant level, and surface level. Bivariate analysis was performed by the use of the Mann-Whitney U-test and stepwise regression analysis was utilized to evaluate the potential influence of confounding factors on the change in peri-implant bone level. RESULTS: The overall mean marginal bone loss for the implant-supported FPDs after 5 years in function was 0.4 mm (SD, 0.76). The bone level change at FPDs placed in the maxilla was significantly greater than that for FPDs in the mandible (0.6 versus 0.2 mm; p<0.05). No statistically significant differences were found with regard to peri-implant bone level change over the 5 years between FPDs with and without cantilevers at any of the levels of comparisons. The multivariate analysis revealed that the variables jaw of treatment and smoking had a significant influence on peri-implant bone level change on the FPD level, but not on the implant or surface levels. The model explained only 10% of the observed variance in the bone level change. CONCLUSION: The study failed to demonstrate that the presence of cantilever extensions in an FPD had an effect on peri-implant bone loss.

Alveolar Bone Loss↗

PubMed2006

Internet and information technology use by dental students in Chile.

As part of a larger cross-country survey of dental students, students from the School of Dentistry, The University of Valparaiso, were invited to participate in a study to describe their use of information and communication technology (ICT). Information was derived from a 124-item questionnaire which included 14 socio-demographic items and 29 items asking about ICT use. ICT items were derived from a University of Birmingham, UK, battery. Data was collected in July and August 2004. A total of 162 of the 249 dental students participated in the study. The average age of students was 21.0 years (SD 2.4 years). The majority of participants (62.1%) were female. All participants had access to a computer, and 96.4% used the Internet. Most students had home Internet connections (73.4%). The most commonly used Internet sites on at least a weekly basis were: email (92.2%); and search engines (88.3%). However, a very few (21.1%) used the Internet to search for dental information for their studies on at least a weekly basis. Furthermore, although the majority (70.4%) found Internet use easy/very easy, 56.2% indicated that any search for information was easy/very easy. The majority (72.2%) indicated that the use of virtual education would not affect their class attendance. The final multivariate model explained 26% of the variance in ICT use, significant predictors for ICT use were gender, year of study, level of difficulty in using Internet, and place of Internet use. However, Internet use was mostly for non-dental purposes.

Adolescent↗

PubMed2004

What's new--what's hot in basic science: American Transplant Congress 2004.

The field of transplantation biology has, in the past year, given rise to several improved models explaining the in vivo phenomena of allograft rejection and acceptance. Although T-cells remain central participants in allorecognition, innate immune cells are increasingly recognized as critical. There is also growing acceptance that T-cell responses can vary widely not only based on their repertoire, but also on their immune experience in general, and their participation in homeostatic proliferation. Additional signaling pathways and molecules, such as the Janus kinase pathway and vascular endothelial growth factor have been added to those recognized as important in pharmacologic immunosuppression, and the concepts of regulation, once polarized between CD8+ and CD4+ camps, have begun to converge upon a recognition that there are many phenotypes of regulatory cells. In addition to improved basic science, several translational fields have accelerated in the past 12 months. Promising and clinically applicable islet transplant regimens have been developed and look appropriate for near-term clinical trials. Significant progress in discordant xenotransplantation is also apparent. This manuscript will review the past year in transplantation science as reported at the 2004 American Transplant Congress.

Animals↗

PubMed2001

Components of variation of surface hoof strain with time.

The relative contribution of a number of random and fixed variables to variation in surface strain magnitudes on the hoof capsule was assessed for healthy feet under normal conditions. Principal strains were recorded in vivo from 5 rosette gauges glued around the circumference of the right forefeet of 4 horses on 4 occasions over a 9 month period. Recordings were made at every other trimming and reshoeing. During each session, gauges were positioned with a template for repeatability. Strains were recorded at the trot and canter (at consistent speeds), for straight motion and turns, and before and after the hoof was trimmed and reset. Up to 30 strides were recorded for each combination of these variables. ANOVAs were performed on midstance strains of 7008 strides to determine the relative contributions to strain variation of individual horse, test day, gait and direction combined as one factor, gauge position on the hoof, trimming, interstride variability and the interactions among these factors. The ANOVA model explained 87% of the variation, of which approximately 84% was due to fixed effects and 16% to random effects. Circumferential position of the gauges and several of the interactions including this term were by far the greatest contributors to strain variation. Differences among gauge positions, individuals and gait + direction are consistent with previous work. This study has added the relative effects, which are small but significant, of trimming on a regular basis and of time. The change in strain magnitudes with trimming was different for each horse, which leads to the possibility that over- and underuse may have to be quantified on an individual basis.

Analysis of Variance↗

PubMed2002

Remodelling inactivation gating of Kv4 channels by KChIP1, a small-molecular-weight calcium-binding protein.

Calcium-binding proteins dubbed KChIPs favour surface expression and modulate inactivation gating of neuronal and cardiac A-type Kv4 channels. To investigate their mechanism of action, Kv4.1 or Kv4.3 were expressed in Xenopus laevis oocytes, either alone or together with KChIP1, and the K+ currents were recorded using the whole-oocyte voltage-clamp and patch-clamp methods. KChIP1 similarly remodels gating of both channels. At positive voltages, KChIP1 slows the early phase of the development of macroscopic inactivation. By contrast, the late phase is accelerated, which allows complete inactivation in < 500 ms. Thus, superimposed traces from control and KChIP1-remodelled currents crossover. KChIP1 also accelerates closed-state inactivation and recovery from inactivation (3- to 5-fold change). The latter effect is dominating and, consequently, the prepulse inactivation curves exhibit depolarizing shifts (DeltaV = 4-12 mV). More favourable closed-state inactivation may also contribute to the overall faster inactivation at positive voltages because Kv4 channels significantly inactivate from the preopen closed state. KChIP1 favours this pathway further by accelerating channel closing. The peak G-V curves are modestly leftward shifted in the presence of KChIP1, but the apparent 'threshold' voltage of current activation remains unaltered. Single Kv4.1 channels exhibited multiple conductance levels that ranged between 1.8 and 5.6 pS in the absence of KChIP1 and between 1.9 and 5.3 pS in its presence. Thus, changes in unitary conductance do not contribute to current upregulation by KChIP1. An allosteric kinetic model explains the kinetic changes by assuming that KChIP1 mainly impairs open-state inactivation, favours channel closing and lowers the energy barrier of closed-state inactivation.

Animals↗

PubMed2002

The mechanical waveform of the basilar membrane. IV. Tone and noise stimuli.

Analysis of mechanical cochlear responses to wide bands of random noise clarifies many effects of cochlear nonlinearity. The previous paper [de Boer and Nuttall, J. Acoust. Soc. Am. 107, 1497-1507 (2000)] illustrates how closely results of computations in a nonlinear cochlear model agree with responses from physiological experiments. In the present paper results for tone stimuli are reported. It was found that the measured frequency response for pure tones differs little from the frequency response associated with a noise signal. For strong stimuli, well into the nonlinear region, tones have to be presented at a specific level with respect to the noise for this to be true. In this report the nonlinear cochlear model originally developed for noise analysis was modified to accommodate pure tones. For this purpose the efficiency with which outer hair cells modify the basilar-membrane response was made into a function of cochlear location based on local excitation. For each experiment, the modified model is able to account for the experimental findings, within 1 or 2 dB. Therefore, the model explains why the type of filtering that tones undergo in the cochlea is essentially the same as that for noise signals (provided the tones are presented at the appropriate level).

Acoustic Stimulation↗

PubMed2003

Spectral models of additive and modulation noise in speech and phonatory excitation signals.

The article presents spectral models of additive and modulation noise in speech. The purpose is to learn about the causes of noise in the spectra of normal and disordered voices and to gauge whether the spectral properties of the perturbations of the phonatory excitation signal can be inferred from the spectral properties of the speech signal. The approach to modeling consists of deducing the Fourier series of the perturbed speech, assuming that the Fourier series of the noise and of the clean monocycle-periodic excitation are known. The models explain published data, take into account the effects of supraglottal tremor, demonstrate the modulation distortion owing to vocal tract filtering, establish conditions under which noise cues of different speech signals may be compared, and predict the impossibility of inferring the spectral properties of the frequency modulating noise from the spectral properties of the frequency modulation noise (e.g., phonatory jitter and frequency tremor). The general conclusion is that only phonatory frequency modulation noise is spectrally relevant. Other types of noise in speech are either epiphenomenal, or their spectral effects are masked by the spectral effects of frequency modulation noise.

Fourier Analysis↗

PubMed2006

Mechanisms of generation of the 2f2-f1 distortion product otoacoustic emission in humans.

The 2f1-f2 distortion product otoacoustic emission (DPOAE) is considered to consist of two components in normally hearing ears, one having constant phase with changing DP frequency (wave fixed) and one having an increasing phase lag with increasing frequency (place fixed). The aim was to identify the wave-fixed and place-fixed components of both 2f1-f2 and 2f2-f1 DPs, and, in particular, to show whether a wave-fixed 2f2-f1 DP exists in normally hearing adults. DPOAE recordings were made in 20 ears of normally hearing young adults. Four frequency ratios were used and recording entailed fixed frequency-ratio sweeps. A separation into wave-fixed and place-fixed components was carried out using a time-window separation method. A method for estimating the noise floor after data processing was developed. Results confirmed the presence of wave-fixed and place-fixed components for 2f1-f2, consistent with previous studies. Both components were also present for 2f2-f1 in virtually all subjects. This latter finding conflicts with current models of DPOAE generation, and so a modified model is proposed. Unlike the 2f1-f2 emission, which has a wave-fixed component that is strongly dependent on the frequency ratio, neither component of the 2f2-f1 emission showed such a dependence. The proposed model explains these findings in terms of the overlap of the primary frequency traveling waves.

Adult↗

PubMed1999

On the lingual organization of the German vowel system.

A hybrid PARAFAC and principal-component model of tongue configuration in vowel production is presented, using a corpus of German vowels in multiple consonant contexts (fleshpoint data for seven speakers at two speech rates from electromagnetic articulography). The PARAFAC approach is attractive for explicitly separating speaker-independent and speaker-dependent effects within a parsimonious linear model. However, it proved impossible to derive a PARAFAC solution of the complete dataset (estimated to require three factors) due to complexities introduced by the consonant contexts. Accordingly, the final model was derived in two stages. First, a two-factor PARAFAC model was extracted. This succeeded; the result was treated as the basic vowel model. Second, the PARAFAC model error was subjected to a separate principal-component analysis for each subject. This revealed a further articulatory component mainly involving tongue-blade activity associated with the flanking consonants. However, the subject-specific details of the mapping from raw fleshpoint coordinates to this component were too complex to be consistent with the PARAFAC framework. The final model explained over 90% of the variance and gave a succinct and physiologically plausible articulatory representation of the German vowel space.

Female↗