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Assembly of transmembrane helices of simple polytopic membrane proteins from sequence conservation patterns.

The transmembrane (TM) domains of most membrane proteins consist of helix bundles. The seemingly simple task of TM helix bundle assembly has turned out to be extremely difficult. This is true even for simple TM helix bundle proteins, i.e., those that have the simple form of compact TM helix bundles. Herein, we present a computational method that is capable of generating native-like structural models for simple TM helix bundle proteins having modest numbers of TM helices based on sequence conservation patterns. Thus, the only requirement for our method is the presence of more than 30 homologous sequences for an accurate extraction of sequence conservation patterns. The prediction method first computes a number of representative well-packed conformations for each pair of contacting TM helices, and then a library of tertiary folds is generated by overlaying overlapping TM helices of the representative conformations. This library is scored using sequence conservation patterns, and a subsequent clustering analysis yields five final models. Assuming that neighboring TM helices in the sequence contact each other (but not that TM helices A and G contact each other), the method produced structural models of Calpha atom root-mean-square deviation (CA RMSD) of 3-5 A from corresponding crystal structures for bacteriorhodopsin, halorhodopsin, sensory rhodopsin II, and rhodopsin. In blind predictions, this type of contact knowledge is not available. Mimicking this, predictions were made for the rotor of the V-type Na(+)-adenosine triphosphatase without such knowledge. The CA RMSD between the best model and its crystal structure is only 3.4 A, and its contact accuracy reaches 55%. Furthermore, the model correctly identifies the binding pocket for sodium ion. These results demonstrate that the method can be readily applied to ab initio structure prediction of simple TM helix bundle proteins having modest numbers of TM helices.

Bacteriorhodopsins↗

[Comparison of health conservation for elders in assisted living facilities and nursing homes].

PURPOSE: This study was performed to evaluate and compare health conservation and its related factors of elders in assisted living facilities or nursing homes. METHOD: Data for health conservation was collected from 316 elders in 10 institutions in Daegu city and Kyungpook province from February 1st to February 22nd, 2005. Data was collected by a structured questionnaire that included general characteristics, general health status, health conservation, functional health status (ADL, IADL) and depression (GDS-K) scales. The collected data was analyzed by the SPSS (version 11.5) program including descriptive statistics, t-test, chi2-test, Pearson's correlation and stepwise method regression analysis. RESULT: The elders in assisted living facilities revealed lower scores in health conservation, ADL and IADL than the elders in nursing homes. Predictable variables influencing health conservation of the elders in assisted living facilities were depression and MAC (Mid-Arm Circumference) that is equal to .270, and the the elders in nursing home were depression, IADL, degree of sleep, and TSF (Triceps Skin Fold) that is equal to .409. CONCLUSION: The development of a health conservation program and long-term health care service system for elders in assisted living facilities are needed than for the elders in nursing homes.

Aged↗

Small-sample performance of the robust score test and its modifications in generalized estimating equations.

The sandwich variance estimator of generalized estimating equations (GEE) may not perform well when the number of independent clusters is small. This could jeopardize the validity of the robust Wald test by causing inflated type I error and lower coverage probability of the corresponding confidence interval than the nominal level. Here, we investigate the small-sample performance of the robust score test for correlated data and propose several modifications to improve the performance. In a simulation study, we compare the robust score test to the robust Wald test for correlated Bernoulli and Poisson data, respectively. It is confirmed that the robust Wald test is too liberal whereas the robust score test is too conservative for small samples. To explain this puzzling operating difference between the two tests, we consider their applications to two special cases, one-sample and two-sample comparisons, thus motivating some modifications to the robust score test. A modification based on a simple adjustment to the usual robust score statistic by a factor of J/(J - 1) (where J is the number of clusters) reduces the conservativeness of the generalized score test. Simulation studies mimicking group-randomized clinical trials with binary and count responses indicated that it may improve the small-sample performance over that of the generalized score and Wald tests with test size closer to the nominal level. Finally, we demonstrate the utility of our proposal by applying it to a group-randomized clinical trial, trying alternative cafeteria options in schools (TACOS).

Adolescent↗

Fixation of nondisplaced scaphoid fractures: making treatment cost effective. Prospective controlled trial.

INTRODUCTION: Nondisplaced scaphoid waist fractures treated with prolonged plaster immobilisation often lead in transient joint stiffness and to a delay in return to sport and work activity. The long time off work increases the work off compensation costs. Internal fixation of scaphoid fractures has resulted in a shorter time to union and to return to work and sports. This prospective study compares cast immobilisation with screw fixation and the direct cost with indirect cost of conservative and minimally invasive treatment of undisplaced scaphoid fractures. MATERIALS AND METHODS: Forty-seven patients with an acute nondisplaced waist fracture of the scaphoid were allocated into either cast immobilisation or internal screw fixation for this study. Cost data concerning the groups of nonoperated and operated patients were analysed. Range of wrist motion, grip strength, DASH-score, time to fracture union, return to work time and the needed physiotherapy at the final follow-up at 6 months were evaluated. RESULTS: Twenty-one patients were included in the group of screw fixation and 23 patients were included in the group of cast immobilisation. At final follow-up there was no significant difference in the range of motion of the wrist or in grip strength. The operatively treated group had a better mean DASH-score than the conservative group. Fracture union was seen in the screw fixation group at a mean of 43 days and in the cast immobilisation group at a mean of 74 days (P < 0.5). The average time of return to work was 8 days for patients who had an internal screw fixation, while those treated with a cast returned to work at a mean of 55 days (P < 0.5). In total the internal fixation of undisplaced scaphoid fractures is less expensive than conservative treatment. CONCLUSION: Internal screw fixation of nondisplaced scaphoid fractures had a shorter time to bony union and the patients returned earlier to work compared with cast immobilisation. Although it is assumed that operative treatment is more expensive, in this study the cost was not found to be higher.

Adult↗

Function of dislocated hips in children with lower level spina bifida.

We reviewed 52 children, born between 1974 and 1985 with spina bifida affecting L3 and L4, who had dislocated hips. Their motor function was stable and they were able to walk at the time of dislocation. They were interviewed and examined physically and radiologically. Physical function was measured by the Rand Health Insurance Study questionnaire (HIS), the Childhood Health Assessment questionnaire (CHAQ), and by determining the functional level of ambulation according to Hoffer et al (1973). In a subgroup of 12 patients with L4 level of involvement from both treatment groups we measured the metabolic energy consumption while walking. Thirty patient (49 hips) had been treated by operative relocation and 22 conservatively. Ten of the hips treated by operation subluxated or redislocated. The function in the two groups (conservative nu operated) was similar (HIS score 7.8 v 8.0, p = 0.45; CHAQ 14 v 13, p = 0.2; level of mobility 0.61 v 0.63, p = 0.5). Patients in whom operation had failed had worse function than did those with successful surgery (HIS score 8.8 v 6.1, p = 0.025) and those with successful surgery had better function than patients treated conservatively (HIS score 8.8 v 8.0, p = 0.15). Function in patients with failed operations, however, was worse than in those who did not have surgical treatment (HIS score 6.6 v 7.8, p = 0.07). In the 12 so examined the operated group had a 30% more energy-efficient gait (0.271 v 0.361 ml O2 kg/m, p = 0.05). Patients with failed operations had worse function than those who were not operated on. The benefit of surgical relocation of the dislocated hips was marginal.

Adolescent↗

Visual impairment, verbal humor, and conservation.

Through a cerebral hemispheric specialization model, I speculated that the reported discrepancy between visually impaired children's competency in language development and lags in cognition may be explained by the use of visual-spatial measurements of cognition. The performance of 51 visually impaired and 51 sighted children, ages 7 to 15 years, on a task of joke comprehension and conservation of weight scores was analyzed. I hypothesized that the ability to comprehend verbal humor would reflect the function of the left hemisphere of the brain and the ability to perform a Piagetian visual-spatial task would reflect the function of the right hemisphere. The findings indicate that although age and IQ contributed significantly to predicting joke comprehension, the ability to conserve did not have a unique contribution. In conclusion, I suggest that the cerebral hemispheric specialization model be considered when investigating language and cognition of visually impaired children.

Adolescent↗

Quality of life after the menopause: a population study.

OBJECTIVE: To assess the impact of menopause and some sociodemographic variables on quality of life (QoL). MATERIALS AND METHODS: Four hundred and eighty-one women aged 40-59 years attending the Southern Metropolitan Health Service in Santiago de Chile were studied using the Specific Quality of Life Questionnaire for Menopause from Toronto University. RESULTS: Univariate analysis showed that menopausal women have worse QoL scores than women conserving cycles in the four areas of the questionnaire: They show a 10.6-fold higher risk for suffering vasomotor disorders affecting QoL, a 3.5-fold higher risk for psychosocial impairment, a 5.7-fold higher risk for physical disorders, and a 3.2-fold higher risk for sexual disorders (P < 0.0001). Regarding the influence of social markers (age, marital status, school years, work, number of children and sexual activity), housewives were found to have higher, worse, scores than working women in all test components (vasomotor, 3.11+/-1.90 versus 2.57+/-1.71, P < 0.003; psychosocial, 3.44+/-1.59 versus 2.92+/-1.45, P < 0.0007; physical, 3.45+/-1.36 versus 2.96+/-1.20, P < 0.0001; sexual, 3.63+/-2.23 versus 2.49+/-1.95, P < 0.0001). However, logistic regression demonstrated that the only variable found to cause a significant impairment in QoL was menopause. CONCLUSION: Menopause causes a decrease in quality of life, which is independent from age and other sociodemographic variables.

Adult↗

Population-based study of the relationship of treatment and sociodemographics on quality of life for early stage breast cancer.

OBJECTIVE: To examine the relationship between cancer stage, surgical treatment and chemotherapy on quality of life (QOL) after breast cancer and determine if sociodemographic characteristics modify the observed relationships. METHODS: A population-based sample of women with Stages 0-II breast cancer in the United States (N = 1357) completed surveys including the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30), and the Breast Cancer-Specific Quality of Life Questionnaire (QLQ BR-23). Regression models calculated mean QOL scores across primary surgical treatment and chemotherapy. Clinically significant differences in QOL were defined as > or = 10 point difference (out of 100) between groups. RESULTS: Meaningful differences in QOL by surgical treatment were limited to body image with women receiving mastectomy with reconstruction reporting lower scores than women receiving breast conserving surgery (p < 0.001). Chemotherapy lowered QOL scores overall across four QOL dimensions (p values < 0.001), with a disproportionately greater impact on those with lower levels of education. Younger women reported lower QOL scores for seven of nine QOL dimensions (p values < 0.001). CONCLUSIONS: Women should be reassured that few QOL differences exist based on surgical treatment, however, clinicians should recognize that the impact of treatment on QOL does vary by a woman's age and educational level.

Adult↗

Conservation throughout vertebrate evolution of the predicted beta-strands in myelin basic protein.

To identify functionally important parts of the 18.5-kDa myelin basic protein (MBP), the amino acid sequences from 10 species ranging from shark to human were aligned using the SEQHP computer program. The residues that are invariant or very conservatively substituted (Arg/Lys, Ser/Thr, Ile/Leu, Asp/Glu) among all 10 proteins were scored. Of the 72 conserved residues in the 170-residue human protein (42% conserved), 32 are found within the five beta-strands previously predicted (45 residues, 71% conserved), 23 within the small-loops region (42 residues, 55% conserved), but only 17 within the large-loops region (83 residues, 20% conserved). Of the 22 hydrophobic residues within the predicted beta-sheet of human MBP, 20 hydrophobic residues remain in the shark protein, 19 of them in the same positions. In contrast, there are 10 hydrophobic residues elsewhere in the human protein, but only 7 remain in the shark protein and only 1 of them is in the same position. The triprolyl sequence found in all mammalian MBPs and in the chicken MBP is not conserved in the shark protein. The four alternately spliced forms of mouse MBP can be accommodated by the beta-structural model, but not the 17-kDa human MBP, which lacks exon 5. These findings confirm the crucial role of the hydrophobic residues in the predicted beta-sheet for the structure and function of the protein. It seems likely that the conserved portions of the protein make an important contribution to the highly ordered lamellar structure of myelin.

Amino Acid Sequence↗

Al-Ain community psychiatric survey IV: socio-cultural changes (traditionality-liberalism) and prevalence of psychiatric disorders.

UNLABELLED: BACKGROUND This study was set to explore the relationship between socio-cultural change and psychopathology. METHOD: A representative sample (n = 1,394) of Al-Ain adult population had their psychopathology assessed with the Composite International Diagnostic Interview and other self-reported questionnaires, while the socio-cultural change was assessed with the modified version of the Socio-cultural Change Questionnaire (ScCQ). The reliability and construct validity of the modified ScCQ were assessed. The overall Tradition Index, attitudinal and behavioural indices of the sample were estimated. Association between socio-cultural change and psychopathology was also evaluated. RESULT: The reliability of the modified ScCQ was found to be moderate (alpha Cronbach 0.66) and the hypothesis regarding its construct validity was confirmed. Mean traditional index was found to be 0.61 +/- 0.14.Young, highly educated, skilled, and female subjects were found to be significantly less conservative and their scores on traditional index deviated significantly from overall mean. Less traditional people were also found to have a significantly increased rate of ICD-10 psychiatric disorder and higher scores on psychopathology measures especially among females. Although females showed significantly more modern attitude, there were no significant sex differences in the expressed behaviour as measured by the behavioural Tradition Index. CONCLUSION: The findings of this study suggest that the prevalence of psychiatric disorder varies significantly according to the extent to which subjects adhere to traditional values.

Adult↗

Fetal biophysical profile and vibratory acoustic stimulation in high-risk pregnancies.

OBJECTIVES: To determine the influence of the non-stress test (NST) on the efficiency of the fetal biophysical profile (FBP) and to test the clinical usefulness of the FBP and its combination with vibratory acoustic stimulation (VAS) in managing high-risk pregnancies. METHODS: One hundred twenty fetuses of preeclamptic patients were included in a prospective study. Five standard variables of the FBP were observed ultrasonically following NST. In cases of non-reactive NST, external VAS was applied and the FBP score calculated and compared with the FBP score before VAS. RESULTS: Of 120 calculated FBPs, 102 (85%) had normal profile scores before VAS and 104 (86.7%) after VAS. No statistically significant difference was found. The sensitivity, specificity, and positive and negative predictive values of the FBP score in predicting poor perinatal outcome were 94.7%, 94.4%, 75% and 99%, respectively. VAS produced a high conversion (58.8%) of non-reactive NST to reactive fetal heart rate pattern. The false-negative rate of the FBP score was 9.8 per 1000, which did not increase after VAS. CONCLUSIONS: The efficiency of the FBP score was not significantly improved by VAS, although a high conversion of non-reactive to reactive NST was produced. The FBP with its three 'acute biophysical variables' was found to be an accurate method of antepartum assessment even without an NST. The low incidence of perinatal complications among patients with normal FBP scores, permits the conservative management of preterm high-risk pregnancies.

Acoustic Stimulation↗

Baseline correction in a two-way randomized blocks design.

Randomized blocks designs are used in clinical psychopharmacology research to test the hypothesis that relative effectiveness of different drug treatments depends on the type of patient being treated. Monte Carlo methods were used to evaluate the adequacies of different approaches to statistical control over baseline differences in such a design with special concern for the treatments x blocks interaction effect. Given the usual assumptions, analysis of covariance (ANCOVA) was shown to provide adequate baseline correction with consequent unbiased tests for the treatments x blocks interaction, as well as the main effect for the randomized treatments. Tests relying on simple pre-post difference scores and percentage change scores evidenced seriously conservative or nonconservative bias in the test for treatments x blocks interaction effect, a bias that depended on the direction of the corresponding interaction effect observed in the baseline measurements alone. This is discussed as a serious matter because the interaction effect in a randomized blocks design is a common basis for the claim of specific indications of drug treatments for particular types of patients.

Humans↗

Depression treatment and satisfaction in a multicultural sample of type 1 and type 2 diabetic patients.

OBJECTIVE: To assess rates of depressive symptoms, depression treatment, and satisfaction in a multicultural sample of individuals with type 1 and type 2 diabetes. RESEARCH DESIGN AND METHODS: This study was conducted with a cross-sectional community-based survey design. RESULTS: The sample (n = 221) was predominantly female (60.3%), had type 2 diabetes (75%), and was middle class with a mean (+/-SD) age of 54 +/- 12 years. A total of 53% were white. Depressive symptoms were assessed using the Center for Epidemiologic Studies Depression Scale (CESD) (mean 16.4 +/- 11.3). Using conservative thresholds (CESD score > or =22), 25.3% of participants reported clinically significant depression. Rates of depression did not differ by ethnic group or diabetes type. The majority (76%) of depressed participants reported treatment (52% antidepressants, 63% mental health providers, 19% alternative healers, and 15% herbal remedies). African Americans were less likely to report any depression treatment, to receive antidepressant medications, or receive treatment from a mental health professional compared with whites. Participants with high depressive symptoms reported general satisfaction with depression treatment experiences. CONCLUSIONS: High rates of depressive symptoms were observed across ethnic groups, yet significant differences in use of depression treatment existed across ethnic groups. Those seeking depression treatment reported satisfaction with a variety of depression treatment modalities. Increased depression screening and treatment may be beneficial for ethnically diverse patients with type 1 and type 2 diabetes.

Adult↗

Radiographic versus clinical extension of Class II carious lesions using an F-speed film.

This study investigated the difference in the apparent radiographic and true clinical extension of Class II carious lesions. Sixty-two lesions in both maxillary and mandibular premolars and molars were radiographed using Insight bitewing film. Class II lesions were scored independently by two masked examiners using an 8-point lesion severity scale. During the restoration process the lesions were dissected in a stepwise fashion from the occlusal aspect. Intraoperative photographs (2x) of the lesions were made, utilizing a novel measurement device in the field as a point of reference. Subsequently, the lesions were all given clinical scores using the same 8-point scale. Statistical analysis showed a significant difference between the true clinical extension of the lesions compared to the radiographic score. "Aggressive" and "Conservative" radiographic diagnoses underestimated the true clinical extent by 0.66 mm and 0.91 mm, respectively. No statistical difference was found between premolars and molars or maxillary and mandibular arches. The results of this study help to define the parameters for making restorative treatment decisions involving Class II carious lesions.

Bicuspid↗

Usefulness of the TIMI risk score in predicting both short- and long-term outcomes in the Veterans Affairs Non-Q-Wave Myocardial Infarction Strategies In-Hospital (VANQWISH) Trial.

We sought to test the validity and clinical utility of the Thrombolysis In Myocardial Infarction (TIMI) risk score for patients who have non-Q-wave myocardial infarction. A post hoc analysis of the Veterans Affairs Non-Q-Wave Infarction Strategies In-Hospital (VANQWISH) Trial was performed, wherein patients were assigned a TIMI risk score from which both 30-day and 12-month outcomes (death, nonfatal myocardial infarction, or urgent revascularization) were assessed. At 30 days, the TIMI risk score showed a close match between observed and predicted probabilities of events after adjustment for overall event rates. The event rate at 30 days was 6% for a score of 0 to 2, 10% for a score of 3, 13% for a score of 4, and 14% for a score of 5 to 7 (p = 0.003 and c statistic 0.59). Discriminative ability of the score was greater in the conservative group at 30 days (p = 0.0004, c statistic 0.67). The score remained modestly predictive of events at 1 year (c statistic 0.60). Conservative strategy patients had better 30-day outcomes than the invasive strategy patients if their score was 0 to 2 (odds ratio 0.24, 95% confidence interval 0.08 to 0.76). No significant difference in outcomes between strategies was detected for a score > or =3. The TIMI risk score provides moderate incremental prognostic information in high-risk patients, during both short- and long-term follow-up.

Aged↗

Quality of life after several treatments for osteoarthritis of the hip.

The purpose of this study was to examine quality of life (QOL) after a rotational acetabular osteotomy (RAO), primary total hip arthroplasty (THA), or conservative treatment (Conservative). A series of 147 patients with osteoarthritis of the hip were grouped according to treatment into the RAO group ( n = 62), THA group ( n = 40), and Conservative group ( n = 45) (treated with medication and rehabilitation alone). The mean age of the RAO group was 40 years, the THA group 54 years, and the Conservative group 50 years. The mean follow-up periods were 3.6, 3.9, and 3.3 years, respectively. All patients were female. As a control group 609 volunteers participating in a town mass screening program were recruited. QOL was determined using the Nottingham Health Profile (NHP). Each area of QOL was evaluated separately in all of the treatment groups at less than 1 year after therapy, at more than 1 year but less than 5 years, and at more than 5 years. With regard to QOL at less than 1 year after therapy, the Conservative group had significantly higher scores for energy, pain, and emotional reaction than the Control group. With regard to physical mobility, all of the treatment groups showed significantly higher scores than the Control group. With regard to QOL at more than 1 year but less than 5 years, the RAO and THA groups showed significantly higher scores than the Control group regarding physical mobility. Regarding pain, the RAO and Conservative groups showed significantly higher scores than the Control group. With regard to QOL at more than 5 years, for physical mobility all of the treatment groups showed significantly higher scores than the Control group. For pain the RAO group showed significantly higher scores than the Control group. NHP is a useful means for evaluating QOL in patients treated for osteoarthritis of the hip.

Acetabulum↗

Analysis and prediction of functionally important sites in proteins.

The rapidly increasing volume of sequence and structure information available for proteins poses the daunting task of determining their functional importance. Computational methods can prove to be very useful in understanding and characterizing the biochemical and evolutionary information contained in this wealth of data, particularly at functionally important sites. Therefore, we perform a detailed survey of compositional and evolutionary constraints at the molecular and biological function level for a large set of known functionally important sites extracted from a wide range of protein families. We compare the degree of conservation across different functional categories and provide detailed statistical insight to decipher the varying evolutionary constraints at functionally important sites. The compositional and evolutionary information at functionally important sites has been compiled into a library of functional templates. We developed a module that predicts functionally important columns (FIC) of an alignment based on the detection of a significant "template match score" to a library template. Our template match score measures an alignment column's similarity to a library template and combines a term explicitly representing a column's residue composition with various evolutionary conservation scores (information content and position-specific scoring matrix-derived statistics). Our benchmarking studies show good sensitivity/specificity for the prediction of functional sites and high accuracy in attributing correct molecular function type to the predicted sites. This prediction method is based on information derived from homologous sequences and no structural information is required. Therefore, this method could be extremely useful for large-scale functional annotation.

Binding Sites↗

Utility assessment for different clinical phases of breast cancer in Taiwan.

BACKGROUND AND PURPOSE: Utility is an important index of health-related quality of life (HRQoL). The purpose of this study was to assess utility in different clinical phases of breast cancer in patients in Taiwan. METHODS: Based on a review of HRQoL literature pertaining to breast cancer and medical records of 979 breast cancer patients admitted to National Taiwan University Hospital from 1991 to 1995, a semi-open checklist describing the diagnosis and treatment activities and impacts of different clinical phases of breast cancer was constructed. The checklist was then reviewed and revised in consultation with surgeons, medical oncologists, radiation oncologists, nurses, and breast cancer patients. Thirty-one clinical and public health experts were invited to assess the utility of each phase with the visual analog scale (VAS), standard gamble (SG), and time trade-off (TTO) methods, according to the description of the average patient's life in the checklist. The Delphi technique was used to reach expert consensus. RESULTS: The VAS utility scores were highest during screening phases (100 or 90), lower in phases of incidental finding of a tumor (75) and diagnosis (70), and lower still in the initial treatment phases, especially during adjuvant chemotherapy (50). The scores improved during the follow-up phases. There was a higher score for breast-conserving surgery (65) than modified radical mastectomy (60) only in the early follow-up phase. The scores for recurrence or metastasis (30) and terminal stage were considerably lower and reached the lowest level (10 in a general ward and 12.5 at home or in a hospice) among all phases. The utility scores assessed by SG and TTO were higher than those assessed by VAS. CONCLUSIONS: In this study, we established a consensus among clinical and public health experts on the impact of different clinical phases of breast cancer on utility. The results of this study may be useful in cross-cultural comparisons and cost-utility analyses for breast cancer.

Adult↗