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Oral hygiene and gingival health in Danish dental students and faculty.

This survey attempted to determine the status of oral cleanliness and gingival health in 150 dental students and 101 faculty members in a dental school. Without advance notice, plaque deposits were scored, using the Plaque Index System, and gingival health was determined using the criteria of the Gingival Index System. The 1st-year students had the poorest hygiene and gingival health. An improvement (P less than 0.01) was noted in the 2nd-year students who were still not in clinical training but had completed a course in preventive dentistry including oral hygiene techniques. Further improvement (P less than 0.05) was found in students participating in the clinical courses (3rd and 4th years). However, some deterioration of both hygiene and gingival status occurred in the senior 5th year. Among the faculty, the best oral hygiene and gingival state were found in members of departments in which clinical work centered around patient motivation toward prevention and tooth conservation. The scores for plaque and gingivitis were worse in the departments of oral surgery, dental materials, orthodontics and the basic science departments. Almost all departments and every class showed a few individuals with very poor oral hygiene. It is suggested that regular patient contact influences the personal attitude toward oral hygiene, and that professional activity and emphasis on different aspects of the curriculum may be reflected in the attitude of health professionals toward oral health.

Adult↗

Structural diversity and evolutionary constraints of oxidative phosphorylation.

The oxidative phosphorylation (OxPhos) system is central to metabolism. The more than 90 structural subunits are encoded by different chromosome categories (autosomal, X, and mtDNA). The system is envisioned as an invariant structure between cells and individuals. However, a comprehensive analysis of the 1,000 Genomes Project data reveals unexpected genetic intra-individual variability resulting from the heterozygosity of diploid autosomal genes, while diversity at the population level is generated by variability in mtDNA. We characterized the different levels of structural constriction at evolutionary and population levels for all OxPhos protein residues. To support this analysis, we developed ConScore, a conservation-based predictor of variant impact within OxPhos proteins (area under the receiver operating characteristic curve [ROC-AUC] = 0.97; area under the precision-recall curve [PR-AUC] = 0.94). Notably, for the nuclear-encoded subunits, we found mechanisms limiting individual variability as allelic imbalance or homozygosity bias. Integrating structural, functional, and genetic data, we highlight the significance of each OxPhos protein position, expanding insights into its role in speciation and disease.

Oxidative Phosphorylation↗

Adjustment outcomes in Chinese patients following one-month recovery from severe acute respiratory syndrome in Hong Kong.

This study aimed to examine the short-term adjustment outcomes including distress, self-esteem, and quality of life among Chinese patients after 1-month recovery from severe acute respiratory syndrome (SARS) in Hong Kong and to investigate the predictive abilities of a set of selected variables on the outcomes. At 1-month recovery, 100 SARS survivors (mean age = 37; 66 women) and 184 community subjects completed self-administered questionnaires. In the General Health Questionnaire-28, 61% of the SARS survivors were identified as distressed cases under a conservative cutoff score of 6. Compared with the community sample, SARS survivors had significantly more distress and poor quality of life. Being a healthcare worker, severity of SARS symptoms, steroid dosage, and social support accounted for a portion of variances of different measures. Early psychiatric screening and intervention may be beneficial for the adjustment of SARS survivors after short-term recovery. Future research on the long-term impact of SARS is recommended.

Adaptation, Psychological↗

Architectural transcription factors collectively shape nuclear radial positioning of chromatin contacts.

The measurement of three-dimensional genome folding in the nucleus, mostly through Hi-C methods, is expressed as contact frequencies between genomic segments, without anchoring to physical axes of the spherical nucleus. Here, we mapped the chromatin contacts along nuclear radial axis and built radial score by factoring in contact frequencies. The chromatin high-order structures exhibit rich diversity along radial axis. Furthermore, the proximal trans contacts retrieved by radial score reveal conserved active/inactive chromatin segregation across intra- and interchromosomal interactions. Ablation of CTCF proteins disrupts chromatin loops with mild changes to chromatin radial positioning. By acutely perturbing multiple transcription factor (TF) occupancy, chromatin loop dissolutions are often accompanied by radial dissociations between two anchors. Our work provides a genome architecture reference map adhering to nuclear physical axis and suggests that multiple architectural TFs collectively shape nuclear positioning of chromatin and their contacts, with contacts serving as forces on chromatin positioning as well.

Chromatin↗

ProfNet, a method to derive profile-profile alignment scoring functions that improves the alignments of distantly related proteins.

BACKGROUND: Profile-profile methods have been used for some years now to detect and align homologous proteins. The best such methods use information from the background distribution of amino acids and substitution tables either when constructing the profiles or in the scoring. This makes the methods dependent on the quality and choice of substitution table as well as the construction of the profiles. Here, we introduce a novel method called ProfNet that is used to derive a profile-profile scoring function. The method optimizes the discrimination between scores of related and unrelated residues and it is fast and straightforward to use. This new method derives a scoring function that is mainly dependent on the actual alignment of residues from a training set, and it does not use any additional information about the background distribution. RESULTS: It is shown that ProfNet improves the discrimination of related and unrelated residues. Further it can be used to improve the alignment of distantly related proteins. CONCLUSION: The best performance is obtained using superfamily related proteins in the training of ProfNet, and a classifier that is related to the distance between the structurally aligned residues. The main difference between the new scoring function and a traditional profile-profile scoring function is that conserved residues on average score higher with the new function.

Models, Genetic↗

Entropy calculator: getting the best from your multiple protein alignments.

Amino acid sequence alignment is an extremely useful tool in protein family analysis. Most family characteristics, such as the localization of functional residues, structural constraints and evolutionary relationships may be retrieved through the observation of the conservation pattern highlighted by the alignments. A quantitative score for the conservation in the alignment allows different stages of an alignment to be compared and consequently the alignment information to be efficiently exploited. Many scoring methods have been proposed during the last three decades. Claude Shannon's theory of communication (1948) paved the way for a consistent scoring of protein alignments by considering the residue (or symbol) frequency. A number of modifications have been proposed since that time, but the core statistical approach is still considered one of the best. By combining many database managing tools for treatment of protein sequences, a ClustalW software integration, a flexible symbols treatment and gap normalization functions, Entropy Calculator software has been developed. This new tool provides a global and optimal approach to multiple sequence alignment scoring by offering an easy graphic interface and a series of modification options that help in interpreting alignments and allow conservation pattern inferences to be performed.

Amino Acid Sequence↗

[Management of duodenal adenomatosis in patients with familial adenomatous polyposis].

AIM OF THE STUDY: To review our global management of duodenal adenomas in patients with familial adenomatous polyposis and report the results of different therapeutic approaches. To present the outcome and possible sequels of pancreaticoduodenectomy. PATIENTS AND METHODS: We identified five cases of duodenal adenomas in patients with familial adenomatous polyposis over a period of 10 years (1992-2001), we followed the progression of their Spigelman score. Results of conservative and surgical treatment were collected. RESULTS: Duodenal adenomas were discovered 5-33 years after the first operation for colonic polyposis. The score of Spigelman was as follows: 2, stage 2; 3, stage 3; 1, stage 4. Endoscopic laser therapy followed by Sulindac prescription was proposed in three cases, with only one success. Duodenopancreatectomy was performed in four patients: once the diagnosis of adenoma was made in one patient, due to Spigelman stage 4 with severe dysplasia, because development of intramucosal carcinoma under surveillance in one patient, and after failure or complication of conservative treatment in two others. Worsening of Spigelman score was observed in two out of four patients submitted to conservative therapy. Correlation between Spigelman score and final examination of the specimen was correct in two cases. There was neither significant morbidity nor long-term nutritional sequel after pancreaticoduodenectomy. CONCLUSION: Duodenal adenomas may recur or progress into malignant degeneration under conservative treatment. The pancreaticoduodenectomy is an acceptable solution for stage 4 of Spigelman, especially when severe dysplasia is present.

Adenomatous Polyposis Coli↗

Improved database searches for orthologous sequences by conditioning on outgroup sequences.

MOTIVATION: Searches of biological sequence databases are usually focussed on distinguishing significant from random matches. However, the increasing abundance of related sequences on databases present a second challenge: to distinguish the evolutionarily most closely related sequences (often orthologues) from more distantly related homologues. This is particularly important when searching a database of partial sequences, where short orthologous sequences from a non-conserved region will score much more poorly than non-orthologous (outgroup) sequences from a conserved region. RESULTS: Such inferences are shown to be improved by conditioning the search results on the scores of an outgroup sequence. The log-odds score for each target sequence identified on the database has the log-odds score of the outgroup sequence subtracted from it. A test group of Caenorhabditis elegans kinase sequences and their identified C.elegans outgroups were searched against a test database of human Expressed Sequence Tag (EST) sequences, where the sets of true target sequences were known in advance. The outgroup conditioned method was shown to identify 58% more true positives ahead of the first false positive, compared to the straightforward search without an outgroup. A test dataset of 151 proteins drawn from the C.elegans genome, where the putative 'outgroup' was assigned automatically, similarly found 50% more true positives using outgroup conditioning. Thus, outgroup conditioning provides a means to improve the results of database searching with little increase in the search computation time.

Algorithms↗

FASTA-SWAP and FASTA-PAT: pattern database searches using combinations of aligned amino acids, and a novel scoring theory.

We introduce two new pattern database search tools that utilize statistical significance and information theory to improve protein function identification. Both the general pattern scoring theory with the specific matrices introduced here and the low redundancy of pattern databases increase search sensitivity and selectivity. Pattern scoring preferentially rewards matches at conserved positions in a pattern with higher scores than matches at variable positions, and assigns more negative scores to mismatches at conserved positions than to mismatches at variable positions. The theory of pattern scoring can be used to create log-odds pattern scores for patterns derived from any set of multiple alignments. This theoretical framework can be used to adapt existing sequence database search tools to pattern analysis. Our FASTA-SWAP and FASTA-PAT tools are extensions of the FASTA program that search a sequence query against a pattern database. In the first step, FASTA-SWAP searches the diagonals of the query sequence and the library pattern for high-scoring segments, while FASTA-PAT performs an extended version of hashing. In the second step, both methods refine the alignments and the scores using dynamic programming. The tools utilize an extremely compact binary representation of all possible combinations of amino acid residues in aligned positions. Our FASTA-SWAP and FASTA-PAT tools are well suited for functional identification of distant relatives that may be missed by sequence database search methods. FASTA-SWAP and FASTA-PAT searches can be performed using our World-Wide Web Server (http://dot.imgen.bcm.tmc.edu:9331/seq-search/Op tions/fastapat.html).

Algorithms↗

Spontaneous intracerebral haematomas: surgical versus conservative treatment based on Glascow Coma Scale score and computer tomography data.

Eighty cases of spontaneous intracerebral haematomas were studied retrospectively in order to find clinical and computer tomography parameters; such parameters would be useful for the neurosurgeon, as criteria in the process of deciding surgical or conservative treatment. We found Glascow Coma Scale (GCS) score on admission an excellent criterion. Scores between 3-5 and 12-14 were a contraindication for surgery. Scores between 6-8 indicated surgery, while scores between 9-11 indicated an increased level of readiness. Up to a haematoma size of 16 cm2, size had no influence on GCS score and surgical mortality. For haematoma size larger than 16 cm2, the percentage of patients with low GCS score had increased substantially as well as the surgically mortality. This study has not revealed any lethal haematoma size. No effect of midline shift on mortality was found when shift did not exceed 5 mm. Hypertension was found in 40% of the patients and increased mortality in both types of treatment.

Adult↗

What does the Keane PTSD scale of the MMPI measure? Repeated measurements in a group of patients with major depression.

We looked at a group of depressed patients in a treatment study, none of whom by study design had Posttraumatic Stress Disorder (PTSD). High scores on the PTSD (PK) scale could only be due to factors other than PTSD. Despite the absence of PTSD, we observed an extremely high false positive rate in a group given the MMPI on multiple occasions. 92% of the subjects had at least one T score at or above 65 on the PK scale. 44% of the men and the women had at least one score at or above the more conservative cutoff (a raw score of 28) recommended by Lyons and Keane. The PK scale is sensitive to depression as well as anxiety and PTSD. The PK scale showed multiple high correlations with clinical and validity scales. It was concluded, in agreement with Miller, Goldberg, and Streiner (1995) and Moody and Kish (1989), that the PK scale is primarily a measure of general dysphoria. In populations with considerable psychopathology, the PK scale does not appear to discriminate between patients with and without PTSD.

Adult↗

eBLOCKs: enumerating conserved protein blocks to achieve maximal sensitivity and specificity.

Classifying proteins into families and superfamilies allows identification of functionally important conserved domains. The motifs and scoring matrices derived from such conserved regions provide computational tools that recognize similar patterns in novel sequences, and thus enable the prediction of protein function for genomes. The eBLOCKs database enumerates a cascade of protein blocks with varied conservation levels for each functional domain. A biologically important region is most stringently conserved among a smaller family of highly similar proteins. The same region is often found in a larger group of more remotely related proteins with a reduced stringency. Through enumeration, highly specific signatures can be generated from blocks with more columns and fewer family members, while highly sensitive signatures can be derived from blocks with fewer columns and more members as in a superfamily. By applying PSI-BLAST and a modified K-means clustering algorithm, eBLOCKs automatically groups protein sequences according to different levels of similarity. Multiple sequence alignments are made and trimmed into a series of ungapped blocks. Motifs and position-specific scoring matrices were derived from eBLOCKs and made available for sequence search and annotation. The eBLOCKs database provides a tool for high-throughput genome annotation with maximal specificity and sensitivity. The eBLOCKs database is freely available on the World Wide Web at http://motif.stanford.edu/eblocks/ to all users for online usage. Academic and not-for-profit institutions wishing copies of the program may contact Douglas L. Brutlag (brutlag@stanford.edu). Commercial firms wishing copies of the program for internal installation may contact Jacqueline Tay at the Stanford Office of Technology Licensing (jacqueline.tay@stanford.edu; http://otl.stanford.edu/).

Algorithms↗

Controlled, prospective trial of psychosocial function before and after continuous positive airway pressure therapy.

The aim of the study was to investigate psychosocial function before and after continuous positive airway pressure (CPAP) therapy, and establish the determinants and consequences of objective CPAP use. In a prospective, parallel-group study, changes in psychosocial scores were compared with conservative management or CPAP therapy for the sleep apnoea/hypopnoea syndrome (SAHS). Patient/partner couples from the top (CPAP treated, n=44) or bottom (conservatively treated, n=25) of a CPAP waiting list rated marital satisfaction (evaluation and nurturing relationship issues, communication and happiness (ENRICH), behavioural questionnaire), health/functional status (Short-Form-36 Health Survey, functional outcomes of sleep questionnaire) and sleepiness (Epworth sleepiness scale). Both groups' ratings at baseline were completed while on conservative therapy. Baseline variables did not differ between groups. At follow-up, all seven summary psychosocial scores were statistically better in CPAP-treated patients, effect sizes (ES) ranging from moderate (0.5 SD: marital satisfaction) to very large (>1.0 SD: patients health, functional status and sleepiness scores). Scores in conservatively-treated patients deteriorated to a small or moderate degree (ES -0.2- -0.7 SD), while those in the CPAP-treated group improved to a larger degree (0.3-1.3 SD). Baseline polysomnographical and psychosocial scores, including marital satisfaction, did not predict objective CPAP use (r<0.3). CPAP use was modestly correlated (r=0.3-0.6) with improvement in all psychosocial areas. Continuous positive airway pressure produced statistically and clinically significant psychosocial improvements, some of large magnitude, in psychosocial function. Determinants of usage were not identified, but benefits and usage were positively correlated.

Health Status↗

Degenerate primer design via clustering.

This paper describes a new strategy for designing degenerate primers for a given multiple alignment of amino acid sequences. Degenerate primers are useful for amplifying homologous genes. However, when a large collection of sequences is considered, no consensus region may exist in the multiple alignment, making it impossible to design a single pair of primers for the collection. In such cases, manual methods are used to find smaller groups from the input collection so that primers can be designed for individual groups. Our strategy proposes an automatic grouping of the input sequences by using clustering techniques. Conserved regions are then detected for each individual group. Conserved regions are scored using a BlockSimilarity score, a novel alignment scoring scheme that is appropriate for this application. Degenerate primers are then designed by reverse translating the conserved amino acid sequences to the corresponding nucleotide sequences. Our program, DePiCt, was written in BioPerl and was tested on the Toll-Interleukin Receptor (TIR)and the non-TIR family of plant resistance genes. Existing programs for degenerate primer design were unable to find primers for these data sets.

Algorithms↗

Empirical statistical estimates for sequence similarity searches.

The FASTA package of sequence comparison programs has been modified to provide accurate statistical estimates for local sequence similarity scores with gaps. These estimates are derived using the extreme value distribution from the mean and variance of the local similarity scores of unrelated sequences after the scores have been corrected for the expected effect of library sequence length. This approach allows accurate estimates to be calculated for both FASTA and Smith-Waterman similarity scores for protein/protein, DNA/DNA, and protein/translated-DNA comparisons. The accuracy of the statistical estimates is summarized for 54 protein families using FASTA and Smith-Waterman scores. Probability estimates calculated from the distribution of similarity scores are generally conservative, as are probabilities calculated using the Altschul-Gish lambda, kappa, and eta parameters. The performance of several alternative methods for correcting similarity scores for library-sequence length was evaluated using 54 protein superfamilies from the PIR39 database and 110 protein families from the Prosite/SwissProt rel. 34 database. Both regression-scaled and Altschul-Gish scaled scores perform significantly better than unscaled Smith-Waterman or FASTA similarity scores. When the Prosite/ SwissProt test set is used, regression-scaled scores perform slightly better; when the PIR database is used, Altschul-Gish scaled scores perform best. Thus, length-corrected similarity scores improve the sensitivity of database searches. Statistical parameters that are derived from the distribution of similarity scores from the thousands of unrelated sequences typically encountered in a database search provide accurate estimates of statistical significance that can be used to infer sequence homology.

Animals↗

Fibroin-modulator-binding protein-1 (FMBP-1) contains a novel DNA-binding domain, repeats of the score and three amino acid peptide (STP), conserved from Caenorhabditis elegans to humans.

The predicted transcriptional regulatory factor for the fibroin gene of the silkworm Bombyx mori, fibroin-modulator-binding protein-1 (FMBP-1), was purified by sequential DNA affinity column chromatography, and cDNA clones corresponding to FMBP-1 were isolated from a library. The N-terminal half of FMBP-1 has a weak similarity to the DNA-binding domain of several transcriptional regulatory factors in higher plants. The C-terminal half contains four tandem repeats of a novel 23 amino acid motif, which we named the score and three amino acid peptide (STP). Other genes containing STP repeats were found in Drosophila, Caenorhabditis elegans, mouse and human. Mutational analysis of FMBP-1 showed that the STP repeats form a novel DNA-binding domain. Sequences flanking STP repeats modulated DNA-binding activity. The FMBP-1 gene was expressed during the fourth to fifth instar. FMBP-1 activity appeared to be regulated at the transcriptional level and by the post-transcriptional modification.

Amino Acid Sequence↗

[Treatment of fibular capsular ligament rupture. A multicenter study].

The treatment of lateral ankle ligament tears has been by conservative and by operative means. 483 patients treated by a number of orthopaedic surgeons, general surgeons and trauma surgeons in Germany over a 2 1/2 year period were questioned one year after the injury. Treatment had been conservatively in 325 patients (tape bandage, elastic bandage, plaster cast, ankle brace, Aircast brace, others) and operatively in 158 patients (primary ligament repair, ligament reconstruction). A 100 point subjective ankle score was used for the 420 patients who responded. The mean score was 90.5 points. The average score of all patients undergoing surgery was 88.2 points, the mean score of all conservatively treated patients was 91.7 points. However, instability on stress radiographs after the injury was less in the conservative group. There was no clear correlation between the initial radiographic instability and the follow-up result. Young patients did better than older patients. The authors recommend conservative, early functional treatment for lateral ankle ligament tears.

Adolescent↗

[Neonatal necrotizing enterocolitis: surgical treatment].

Since December 1984 to July 1987, 18 patients with NEC were studied. Vásquez-Estévez's protocol, was applied in order to define the surgical indication, taking in to account ten different clinical and laboratory parameters, each one scored 0 to 3 points. Only patients with score 15 or more should be operated and this was the case in 30% of our NEC. In all surgically treated patients intestinal necrosis was a constant finding, two of them had also bowel perforations. No patients died in the conservative management group (score under 15). Lethality among operated subjects was 16%.

Enterocolitis, Pseudomembranous↗