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At least 685 records · Page 38Linked to original sources
PubMed2007

Does cancer risk affect health-related quality of life in patients with Barrett's esophagus?

BACKGROUND: Health-related quality of life is decreased in patients with GERD and Barrett's esophagus (BE). OBJECTIVE: To determine whether time-tradeoff (TTO) values would differ in patients with BE when patients were asked to trade away the potential risk of esophageal adenocarcinoma rather than chronic heartburn symptoms. DESIGN: A prospective clinical trial. PATIENTS: Subjects with biopsy-proven BE. INTERVENTIONS: Custom-designed computer program to elicit health-state utility values, quality of life in reflux and dyspepsia (QOLRAD), and Medical Outcomes Survey short form-36 surveys. MAIN OUTCOME MEASUREMENTS: TTO utility values for the annual cancer-risk-associated current health state and for hypothetical scenarios of dysplasia and esophageal cancer. RESULTS: We studied 60 patients in the cancer-risk cohort (57 men, 92% veteran; mean age [standard deviation; SD], 65 years [11 years], mean GERD duration 17 years [12 years]). The heartburn cohort included 40 patients with GERD and BE with TTO values derived for GERD symptoms. The mean (SD) utility for nondysplastic BE was 0.91 (0.13) compared with 0.90 (0.12) for the heartburn cohort (P = .7). The mean utility values were significantly lower for scenarios of low-grade dysplasia (0.85 [0.12], P = .02) and high-grade dysplasia (0.77 [0.14], P < .005). The mean TTO was 0.67 (0.19) for the scenario of esophageal cancer. There was no correlation between the utility scores and the disease-specific survey scores. LIMITATIONS: TTO values were hypothetical for states of dysplasia and cancer. CONCLUSIONS: TTO utility values based on heartburn symptoms or annual risk of cancer in patients with nondysplastic BE are roughly equivalent. However, TTO utility values are significantly lower for health states with increasing cancer risks.

Adenocarcinoma↗
PubMed2006

CT imaging of wet specimens from a pathology museum: How to build a "virtual museum" for radiopathological correlation teaching.

X-rays and CT have been used to examine specimens such as human remains, mummies and formalin-fixed specimens. However, CT has not been used to study formalin-fixed wet specimens within their containers. The purpose of our study is firstly to demonstrate the role of CT as a non-destructive imaging method for the study of wet pathological specimens and secondly to use the CT data as a method for teaching pathological and radiological correlation. CT scanning of 31 musculoskeletal specimens from a pathology museum was carried out. Images were reconstructed using both soft-tissue and bone algorithms. Further processing of the data produced coronal and sagittal reformats of each specimen. The container and storage solution were manually removed using Volume Viewer Voxtool software to produce a 3D reconstruction of each specimen. Photographs of each specimen (container and close-up) were displayed alongside selected coronal, sagittal, 3D reconstructions and cine sequences in a specially designed computer program. CT is a non-destructive imaging modality for building didactic materials from wet specimens in a Pathology Museum, for teaching radiological and pathological correlation.

Algorithms↗
PubMed2004

Medical researchers evaluate their methodological skills.

BACKGROUND AND OBJECTIVE: Clinical epidemiology and statistics skills of clinical researchers are often limited. We assessed methodological skills of medical researchers and identified factors associated with higher skill levels. METHODS: In a cross-sectional mail survey at two Swiss teaching hospitals, participants (N=409) rated their ability to perform 26 research-related activities, such as identifying the research question, selecting a study design, computing the required sample size, performing data analysis, and reporting results. RESULTS: The proportion of respondents who were able to perform a specific activity was 33.2% on average, ranging from 1.5% for "numerical statistics (bootstrap, simulation, cross-validation,...)" to 76.0% for "oral presentation of results." The overall skill level (expressed as a percentage of the 26 activities) was associated with principal investigator experience (+8.7%), greater percentage of time devoted to research (+12.4% for near full-time versus no time commitment), years of research experience (+17.6% for 15-40 years versus 0 years), past number of clinical research projects (+18.0% for 15-230 projects versus 0-1 projects), and hours of formal methodological training (+32.6% for 200-1200 hours versus 0-9 hours). CONCLUSION: Self-reported methodological skills were generally modest. The most important covariates of skill levels were current time commitment to research, past experience, and formal training.

Adult↗
PubMed2005

X-ray structure of a water-soluble analog of the membrane protein phospholamban: sequence determinants defining the topology of tetrameric and pentameric coiled coils.

Phospholamban (PLB) is a pentameric transmembrane protein that regulates the Ca(2+)-dependent ATPase SERCA2a in sarcoplasmic reticulum membranes. We previously described the computational design of a water-soluble variant of phospholamban, WSPLB, which reproduced many of the structural and functional properties of the native membrane-soluble protein. While the full-length WSPLB forms a pentamer in solution, a truncated variant forms very stable tetramers. To obtain insight into the tetramer-pentamer cytoplasmic switch, we solved the crystal structure of the truncated construct, WSPLB 21-52. This peptide has a heptad sequence repeat with Leu residues at a- and Ile at d-positions from residues 31-52. The crystal structure revealed that WSPLB 21-52 adopted an antiparallel tetrameric coiled coil. This topology contrasts with the parallel topology of an analogue of the coiled-coil of GCN4 with the same Leu(a) Ile(d) repeat. Analysis of these structures revealed how the nature of the partially exposed residues at e- and g-positions influence the topology formed by the bundle. We also constructed a model for the pentameric form of PLB using the coiled-coil parameters derived from a single monomer in the tetrameric structure. This model suggests that both buried and interfacial hydrogen bonds are important for stabilizing the parallel pentamer.

Amino Acid Sequence↗
PubMed2005

Progress toward an ambulatory pump-lung.

OBJECTIVES: Currently available therapies for acute and chronic lung diseases have not been effective and have various problems associated with the technologies used. We present a novel active mixing pump-lung with the goal of providing total respiratory support to ambulatory patients. METHODS: The pump-lung is based on the concept of active mixing oxygenation within a constrained vortex. The rotation of hollow-fiber membranes disrupts the concentration boundary layer, increasing gas exchange efficiency, and simultaneously pumps the blood. Consequently, the amount of membranes required to achieve gas transfer sufficient for total respiratory support is considerably small. A series of studies, including computational design, experimental bench testing, and in vivo animal experiments, have been performed to implement this concept into a viable artificial pump-lung device. RESULTS: A series of pump-lung prototypes with a membrane surface area of 0.17 to 0.5 m2 were designed and characterized in vitro with bovine blood, demonstrating extremely high gas exchange efficiency. The prototype with a gas exchange surface area of 0.5 m2 was evaluated in calves. The device provided oxygen transfer of approximately 115 mL/min for respiratory support of an animal for up to 5 days. CONCLUSIONS: Progress to date suggests a high likelihood of success for an extracorporeal shorter-term lung that can be switched in and out like dialysis devices. Our device is unique in that it incorporates an integrated pumping and active mixing principle for excellent gas transfer and eliminates the need of the native right ventricle's ability to power blood through the artificial and natural lungs.

Animals↗
PubMed2006

Directed evolution of enzymes and biosynthetic pathways.

Directed evolution is an important tool for overcoming the limitations of natural enzymes as biocatalysts. Recent advances have focused on applying directed evolution to a variety of enzymes, such as epoxide hydrolase, glyphosate N-acetyltransferase, xylanase and phosphotriesterase, in order to improve their activity, selectivity, stability and solubility. The focus has also shifted to manipulating biosynthetic pathways for the production of many naturally synthesized compounds, as well as the production of novel 'unnatural' compounds. A combined directed evolution and computational design approach is becoming increasingly important in exploring enzyme sequence-space and creating improved or novel enzymes. Fueled by recent breakthroughs in genomics and metagenomics, these developments should help expand the use of biocatalysts in industry.

Anti-Infective Agents↗
PubMed2006

Prediction of MHC-binding peptides of flexible lengths from sequence-derived structural and physicochemical properties.

Peptide binding to MHC is critical for antigen recognition by T-cells. To facilitate vaccine design, computational methods have been developed for predicting MHC-binding peptides, which achieve impressive prediction accuracies of 70-90% for binders and 40-80% for non-binders. These methods have been developed for peptides of fixed lengths, for a limited number of alleles, trained from small number of non-binders, and in some cases based straightforwardly on sequence. These limit prediction coverage and accuracy particularly for non-binders. It is desirable to explore methods that predict binders of flexible lengths from sequence-derived physicochemical properties and trained from diverse sets of non-binders. This work explores support vector machines (SVM) as such a method for developing prediction systems of 18 MHC class I and 12 class II alleles by using 4208-3252 binders and 234,333-168,793 non-binders, and evaluated by an independent set of 545-476 binders and 110,564-84,430 non-binders. Binder accuracies are 86-99% for 25 and 70-80% for 5 alleles, non-binder accuracies are 96-99% for 30 alleles. Binder accuracies are comparable and non-binder accuracies substantially improved against other results. Our method correctly predicts 73.3% of the 15 newly-published epitopes in the last 4 months of 2005. Of the 251 recently-published HLA-A*0201 non-epitopes predicted as binders by other methods, 63 are predicted as binders by our method. Screening of HIV-1 genome shows that, compared to other methods, a comparable percentage (75-100%) of its known epitopes is correctly predicted, while a lower percentage (0.01-5% for 24 and 5-8% for 6 alleles) of its constituent peptides are predicted as binders. Our software can be accessed at .

Alleles↗
PubMed2004

The neural bases of cooperation and competition: an fMRI investigation.

Cooperation and competition are two basic modes of social cognition that necessitate monitoring of both one's own and others' actions, as well as adopting a specific mental set. In this fMRI, study individuals played a specially designed computer game, according to a set of predefined rules, either in cooperation with or in competition against another person. The hemodynamic response during these conditions was contrasted to that of the same subjects playing the game independently. Both cooperation and competition stances resulted in activation of a common frontoparietal network subserving executive functions, as well as the anterior insula, involved in autonomic arousal. Moreover, distinct regions were found to be selectively associated with cooperation and competition, notably the orbitofrontal cortex in the former and the inferior parietal and medial prefrontal cortices in the latter. This pattern reflects the different mental frameworks implicated in being cooperative versus competitive with another person. In accordance with evidence from evolutionary psychology as well as from developmental psychology, we argue that cooperation is a socially rewarding process and is associated with specific left medial orbitofrontal cortex involvement.

Adult↗
PubMed2004

Recurrent pneumoparotid: cause and treatment.

OBJECTIVE: To document the etiology and successful treatment of severe recurrent pneumoparotid. STUDY DESIGN: Computed tomography, ductal measurement by probe size, surgical treatment. RESULTS: We performed a superficial parotidectomy for a 13-year-old with a history of recurrent parotitis. He subsequently developed recurrent pneumoparotid in the contralateral gland with subcutaneous dissection of air into the face, neck, and mediastinum. At surgery, Stensen's ducts were measured and found to be abnormally patent bilaterally compared to standardized norms. Parotid duct ligation, commonly used for sialorrhea, was employed as a novel treatment and was curative. CONCLUSION: Insufflation of air into the parotid duct system can trouble woodwind instrument players, can complicate dental procedures, or can be self-induced. It is generally a benign condition requiring no therapy. Occasionally, pneumoparotid can be recurrent and lead to inflammation and infection of the parotid or subcutaneous emphysema. SIGNIFICANCE: In selected cases of recurrent pneumoparotid, ductal ligation may be curative.

Adolescent↗
PubMed2006

High-resolution protein-protein docking.

The high-resolution prediction of protein-protein docking can now create structures with atomic-level accuracy. This progress arises from both improvements in the rapid sampling of conformations and increased accuracy of binding free energy calculations. Consequently, the quality of models submitted to the blind prediction challenge CAPRI (Critical Assessment of PRedicted Interactions) has steadily increased, including complexes predicted from homology structures of one binding partner and complexes with atomic accuracy at the interface. By exploiting experimental information, docking has created model structures for real applications, even when confronted with challenges such as moving backbones and uncertain monomer structures. Work remains to be done in docking large or flexible proteins, ranking models consistently, and producing models accurate enough to allow computational design of higher affinities or specificities.

Animals↗
PubMed2026

Multitarget interactions of bisphenol A in polycystic ovary syndrome: evidence from integrated network toxicology, mendelian randomization, and molecular docking.

OBJECTIVE: To study the potential pathogenic mechanisms of bisphenol A (BPA) in polycystic ovary syndrome (PCOS) using an integrative computational strategy. DESIGN: Integrative computational study combining network toxicology, Mendelian randomization (MR), and molecular docking. SUBJECTS: For MR analysis, genetic data were sourced from large European-ancestry cohorts, including plasma protein quantitative trait loci data and genome-wide association study summary statistics for PCOS (3,045 cases and 267,780 controls). EXPOSURE: In silico exposure to BPA for target prediction; genetically predicted plasma protein levels for causal inference. MAIN OUTCOME MEASURES: Identification of overlapping targets between BPA and PCOS; functional enrichment pathways; causal effects of prioritized proteins on PCOS risk (odds ratios with 95% confidence intervals); binding affinities between BPA and core targets (kcal/mol). RESULTS: Network toxicology identified 310 overlapping targets between BPA and PCOS. Enrichment analyses revealed significant involvement in endocrine signaling, inflammatory pathways (eg, IL-17), and cellular processes. MR demonstrated that genetically elevated levels of RET, CXCL8, HTR6, MMP1, MMP9, NTRK1, and TNNI2 were significantly associated with increased PCOS risk, whereas higher PSAP and SHBG levels were protective. Molecular docking confirmed stable binding between BPA and all nine key targets, with strongest affinity for SHBG (-8.4 kcal/mol), followed by NTRK1, TNNI2, and RET. CONCLUSION: This integrative investigation suggests that BPA may contribute to PCOS pathogenesis through multitarget interactions involving inflammatory mediators, endocrine regulators, and tissue remodeling proteins. The findings provide prioritized targets and mechanistic insights for future experimental validation and environmental risk assessment.

Female↗
PubMed1998

Probabilities for singleton and multiple pregnancies after in vitro fertilization.

OBJECTIVE: To help physicians provide risk estimates for specific pregnancy outcomes. DESIGN: Computation of exact binomial probabilities for singleton and multiple pregnancies as a function of two inputs: the number of embryos transferred and the implantation rate. Inputs were varied over the range of values reported in the literature. MAIN OUTCOME MEASURE(S): Probabilities for a singleton pregnancy (none), a multiple pregnancy (Pmult), and no pregnancy (Pnone) after one IVF cycle. RESULT(S): Given a 30% implantation rate and three embryos transferred, Pone=.44, Pmult=.22, and Pnone=.34. Although further increasing the number of embryos transferred increases the chance of pregnancy, it also raises the probability of a multiple pregnancy and lowers the chance of a singleton pregnancy. Although varying the implantation rate changes the specific probability estimates, the same trade-off persists. CONCLUSION(S): Those who consider an IVF "success" to be a singleton pregnancy should be attentive to the number of embryos transferred. Infertility therapy may be one area in medicine where more is not necessarily better.

Adult↗
PubMed1999

An analytical model of lumbar motion segment in flexion.

OBJECTIVE: To develop an analytical model of the lumbar motion segment and to determine the following under the application of flexion physiological loads: (1) the force displacement relationships of the lumbar motion segment; (2) the forces in the ligaments, disc, and facet joints; (3) the strains in the ligaments; and (4) the effect of the transection of the ligaments. DESIGN: Computer modeling. SETTING: Spinal Ergonomics and Joint Research Laboratory at The National College of Chiropractic. PROCEDURE: Computer model simulation of external loads and simulation of ligament transection. MEASURES: The following parameters were predicted in flexion by means of a computer model: (1) the load-displacement relationships of the lumbar motion segment; (2) the loads in the ligaments, disc and facet joints; (3) the strains in the ligaments; and (4) the effect of the transection of the ligaments. RESULTS: The load sharing among different ligaments predicted by this model under flexion load suggests that the supraspinous ligament carries the greatest load, followed by the yellow ligament, capsular ligament, intertransverse ligament, and interspinous ligament. The ligament strains indicate that the supraspinous ligament undergoes the maximum increase in length, followed by the interspinous ligament, yellow ligament, capsular ligament, and intertransverse ligament. The transection of ligaments increased the flexibility of the joint, the strains on the rest of the ligaments, the loads on all of the rest of the ligaments, as well as the moment on the disc, but does not significantly affect the compressive load on the disc. CONCLUSIONS: The analytical model predicts results similar to the experimental data on cadaver motion segments reported in the literature under flexion moment loads.

Computer Simulation↗
PubMed1998

Risk factors for noncompliance with glaucoma follow-up visits in a residents' eye clinic.

OBJECTIVE: This study aimed to identify factors associated with compliance with glaucoma follow-up visits. DESIGN: Computer records of a university residents' eye clinic were reviewed to identify a random sample of all persons who had an examination with International Classification of Disease (ICD) 9 coding (ICD9) for glaucoma suspect or glaucoma during a 2-year period (1991-1993) to undergo telephone interview. PARTICIPANTS: Those who were seen at least every 6 months regardless of earlier return instructions were defined as compliant with follow-up (controls, n = 362). Those who had any lapse between visits of longer than 6 months were defined as noncompliant (cases, n = 362). RESULTS: Interviews were completed for 196 cases and 242 controls. Noncompliant persons were significantly more likely to be suspects for glaucoma rather than to have definite glaucoma and to be dissatisfied with waiting time in the clinic (29.1% vs. 17.8%, P < 0.005) and to state that they did not take their glaucoma medications as prescribed (25.4% vs. 13.4%, P < 0.004). They also were less likely to have been prescribed eyedrop medication. A high percentage of both patients and controls knew that glaucoma can lead to blindness (85.2% and 88.4%, respectively). The most common reasons patients gave for not keeping follow-up visits were the perception that their eye problem was "not serious enough," the cost of examinations, and that the doctor did not tell them to come back. CONCLUSION: Compliance with follow-up visits for glaucoma is associated with markers for early disease. Attempts to improve compliance might focus on improved communication of the seriousness of the disease and improvements in clinic waiting time.

Aged↗
PubMed1997

Biomechanics of the hip joint capsule -- a mathematical model and clinical implications.

OBJECTIVE: Our aim was to develop a mathematical model to calculate forces, tension and stretching in the hip joint capsule, under conditions caused by the joint effusion usually accompanying hip disease. DESIGN: A mathematical model was developed, based on experimental data from cadaver studies. BACKGROUND: Intracapsular pressure is important with respect to the degree of painless movement in the hip. Previously, we established the relations between the rotation around the axis of the neck of the femur, joint effusion, intracapsular pressure and joint stability. METHODS: In six cadaver adult hips the joint distraction, the traction force along and the rotation around the axis of the neck of the femur and the intracapsular pressure, were simultaneously monitored as the volume of intracapsularly infused saline was increased. The elasticity-constants included in the extracted formula for the fluid pressure were calculated in a designed computer software based on these experimental data. RESULTS: Presented in Figures 3-12. CONCLUSIONS: In the normal joint there is no increase in intracapsular pressure, nor any tension in the hyperboloid shape capsule within the normal range of rotation around the axis of the neck of the femur. This shape is distorted in a hip with effusion, rotation then resulting in an increased intracapsular pressure and tension in the capsule, with potential risk of ruptures.

Journal Article↗
PubMed1998

Bedside application of the Neonatal Facial Coding System in pain assessment of premature neonates.

Assessment of infant pain is a pressing concern, especially within the context of neonatal intensive care where infants may be exposed to prolonged and repeated pain during lengthy hospitalization. In the present study the feasibility of carrying out the complete Neonatal Facial Coding System (NFCS) in real time at bedside, specifically reliability, construct and concurrent validity, was evaluated in a tertiary level Neonatal Intensive Care Unit (NICU). Heel lance was used as a model of procedural pain, and observed with n = 40 infants at 32 weeks gestational age. Infant sleep/wake state, NFCS facial activity and specific hand movements were coded during baseline, unwrap, swab, heel lance, squeezing and recovery events. Heart rate was recorded continuously and digitally sampled using a custom designed computer system. Repeated measures analysis of variance (ANOVA) showed statistically significant differences across events for facial activity (P < 0.0001) and heart rate (P < 0.0001). Planned comparisons showed facial activity unchanged during baseline, swab and unwrap, then increased significantly during heel lance (P < 0.0001), increased further during squeezing (P < 0.003), then decreased during recovery (P < 0.0001). Systematic shifts in sleep/wake state were apparent. Rise in facial activity was consistent with increased heart rate, except that facial activity more closely paralleled initiation of the invasive event. Thus facial display was more specific to tissue damage compared with heart rate. Inter-observer reliability was high. Construct validity of the NFCS at bedside was demonstrated as invasive procedures were distinguished from tactile. While bedside coding of behavior does not permit raters to be blind to events, mechanical recording of heart rate allowed for an independent source of concurrent validation for bedside application of the NFCS scale.

Facial Expression↗
PubMedDate not supplied

Evaluating two self-help interventions for smokeless tobacco cessation.

The need for effective, low-cost self-help treatment methods for smokeless tobacco (ST) addiction becomes more evident as rates of product use and associated morbidities increase. This study evaluated two self-help methods for ST cessation. One hundred ninety-eight ST users were randomized into two conditions: half received the LifeSign, a credit card-sized computer designed for gradual ST cessation, and half received the Enough Snuff self-help manual and a video. Subjects in both conditions received telephone support for their quit effort. The study was conducted entirely through phone and mail, allowing delivery of the intervention to both rural and urban users. Self-reported rates of sustained abstinence (no tobacco use at two months and six months) were 24.5% for the manual/video condition, and 18.4%, for the LifeSign condition.

Adolescent↗
PubMed1999

Impact of targeting deviations on outcome in medulloblastoma: study of the French Society of Pediatric Oncology (SFOP).

PURPOSE: To correlate targeting deviation in external beam radiation therapy with site of relapse in a prospective study of 174 patients treated for medulloblastoma. METHODS AND MATERIALS: Between February 1992 and February 1998 the radiotherapy treatment records were reviewed by a panel of radiation oncologists for 174 children treated with radiation therapy for medulloblastoma. The review was done without knowledge of patient outcome. Patterns of relapse were correlated with the results of the quality control review. RESULTS: Among the 174 patients five relapsed before the start of radiotherapy. One hundred sixty-nine patients were evaluable for correlation between targeting deviation and site of relapse. Number of major deviations in radiation therapy treatment is strongly correlated with the risk of tumor relapse (67% [95% CI: 28-91] of 3-year relapse rate in patient group with 2 major deviations and 78% [95% CI: 35-96] with 3 major deviations). This is particularly correlated with relapse in the frontal region of the brain: 5 relapses occurred in the frontal region in patients with major deviation in this area. An erroneous choice of electron beam energy is also linked with craniospinal fluid (CSF) relapse (3-year relapse rate of 68% [95% CI: 42-86]). Minor deviations in therapy technique are slightly associated with an increased risk of relapse in the same range as the group with only one major deviation. CONCLUSION: The quality of medulloblastoma radiation therapy technique is strongly correlated with outcome. Pretreatment central quality assurance review or standardized computer-designed blocks would improve survival to an extent equivalent to that attributed to adjuvant chemotherapy.

Adolescent↗