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Intensified treatment and education of type 1 diabetes as clinical routine. A nationwide quality-circle experience in Germany. ASD (the Working Group on Structured Diabetes Therapy of the German Diabetes Association).

This contribution describes the nationwide implementation of an intensive treatment and education program for type 1 diabetic patients in the clinical routine of the German health care system. Based on the formation of a working group (Arbeitsgemeinschaft Strukturierte Diabetestherapie [ASD]) of presently 57 general internal medicine departments, mainly from secondary and tertiary care levels in city and country hospitals throughout the country, a peer-review quality circle was formed as an official working group of the German Diabetes Association. The participating institutions performed a structured program of intensive treatment and education in all type 1 diabetic patients referred to them on a routine basis. The program includes multiple daily insulin injections or continuous subcutaneous insulin infusion, several times daily blood glucose self-monitoring and self-adaptation of insulin dosages and other aspects of treatment by the patients, and a far-reaching liberalization of the nutrition regimen. The group has attempted to document and to improve the quality of the structure and process of type 1 diabetes care in its participating institutions by a system of peer supervision. Furthermore, all member institutions volunteered to collect outcome data based on systematic 1-1.3 years' follow-up examinations of consecutive type 1 diabetic patients. For the 1997 evaluation of 1,103 type 1 diabetic patients, significant decreases of GHb levels and of incidence rates of severe hypoglycemia (from 0.35 to 0.16 cases per patient-year) and ketoacidosis (from 0.08 to 0.02 cases per patient-year) are presented. The ASD quality circle represents a model to improve principal aspects of type 1 diabetes care on a nationwide basis.

Cohort Studies↗

Tendency-distance models of social cohesion in animal groups.

Although it has been assumed that attraction and repulsion between social individuals constitute a basis for group cohesion, there has been no systematic study of the possible ways in which these tendencies might vary with inter-individual distance (IID), or of associated implications for group structure. In this paper, a family of attraction/repulsion--distance functions is described. Computer simulation was used to examine the effects of each function on group cohesion, as reflected by mean values and variability in IID and group shape. Our results showed that: (a) all models led to stability in group structure, but differed significantly in terms of stable IID and group shape characteristics; (b) cohesion was best served by an upwardly convex behaviour--distance function in which maximum attraction equaled maximum repulsion (and the biological plausibility of this function is discussed); (c) group elongation and variability in mean IID were significantly positively correlated; (d) although dyads maintained an equilibrial separation distance, at which attraction balanced repulsion, in larger groups stable nearest neighbour distances were often less than the equilibrium distance; and (e) individuals needed to monitor and respond to only relatively few of their companions in order to avoid group fragmentation.

Animals↗

Conserved thermochemistry of guanosine nucleophile binding for structurally distinct group I ribozymes.

We report thermodynamic values for binding of the guanosine nucleophile to the ribozyme derived from the Anabaena group I intron, and find that they are similar to those measured previously for the structurally distinct Tetrahymena ribozyme. The free energy of binding guanosine 5'-monophosphate (pG) at 30 degrees C is similar for the two ribozymes. The delta(H)degrees' and delta(S)degrees' for pG binding to the Anabaena ribozyme--RNA substrate complex (E x S) are 3.4 +/- 4 kcal/mol and 27 +/- 10 e.u., respectively. The negligible enthalpic contribution and positive entropy change were found previously for the Tetrahymena ribozyme, and are considered remarkable for a hydrogen-bonding interaction between a nucleotide and a nucleic acid. These thermodynamic values may reflect conformational changes or water release upon pG binding that are comparable for the two ribozymes. In addition, the apparent chemical steps of the two ribozyme reactions share similar activation energies and a positive deltaS++. It now appears that such thermochemical values for guanosine binding and activation may be intrinsic properties of the group I intron catalytic center.

Anabaena↗

Using research to implement change: the introduction of group activities on a psychiatric unit.

Staff in a psychiatric unit of a general hospital proposed the introduction of a programme of structured group activities, based on their casual observation that patients were sometimes unoccupied and bored. It was decided to collect data systematically in order to inform the implementation of activities. An activities record sheet was developed to list all activities taking place over a 1-week period. Questionnaires were administered to patients (n = 23) and staff (n = 20) on the unit to seek their views on the value, type, timing, frequency and location of activities as well as on other related aspects. Overall, staff made practical and realistic suggestions regarding the implementation of structured group activities. The data collected, although useful in planning change, raised questions about the poor quality of patients' responses and the low response rate (50%) from staff. Implications of these and other issues are discussed.

Clinical Nursing Research↗

HIV prevention community planning: challenges and opportunities for data-informed decision-making.

The use of data in decision-making by the Massachusetts Prevention Planning Group (MPPG) was assessed using multiple methods: in-depth interviews, member surveys, directed observations, and archival review. Three factors known to influence group decision-making were of interest: (1) member characteristics, (2) group structure, and (3) data inputs. Membership characteristics were not related to reliance on data. However, group structure factors and data inputs were directly related to reliance on data. Most members accepted an advisory role and felt participation was worthwhile. About half were dissatisfied with decision-making processes, citing member conflicts and distrust. Incompleteness of data, inadequate presentation quality, and lengthy intervals between presentations and actual decision-making were identified as deficits. Although most members reported skills with HIV- and intervention-related data, most also reported deficiencies in interpreting evaluation and cost-effectiveness studies. Member trust and use of data in decision-making could be improved by clarifying decision-making structures and processes, assuring high-quality data presentations, and supporting or training members to better interpret and use data.

Committee Membership↗

Conserved sequences and structures of group I introns: building an active site for RNA catalysis--a review.

Group I introns fold to form an active site to mediate their own RNA splicing. Sequence elements conserved among the available set of 66 group I introns are compiled. Comparative sequence analysis leads to the prediction of some conserved structural features that have not been widely appreciated. The possible significance of conserved nucleotides within base-paired duplexes is discussed; they might be involved in base triplets or alternate pairing interactions.

Introns↗

Tryptophanyl transfer ribonucleic acid synthetase of Escherichia coli. Character of required thiol group and structure of thiol peptides.

Native tryptophanyl-tRNA synthetase purified from Escherichia coli B has on each identical subunit a single thiol group which rapidly forms a mixed disulfide with a thionitrobenzoate moiety of 5,5'-dithiobis(2-nitrobenzoic acid). The reaction and the concomitant inactivation of the enzyme are both reversible by reductive removal of the thionitrobenzoate with dithiothreitol. Iodoacetamide and N-ethylmaleimide also react with the thiol group required for enzyme activity, but iodoacetic acid inactivates the enzyme through another mechanism. Three or 4 half-cystine residues/subunit were detected by amino acid analysis and by titration of the denatured enzyme with 5,5'-dithiobis(2-nitrobenzoic acid); no disulfide bonds were detected by borohydride reduction. Cleavage of the subunit (molecular weight 37,000) with 2-nitro-5-thiocyanobenzoic acid gave fragments of molecular weights 32,000, 27,000, and 9,500. Five carboxymethylated peptides were isolated from the trypsin products of the denatured enzyme after treatment with iodo[14C]lacetate. Three of these peptides represented unique sequences surrounding thiol groups in the enzyme. One cysteine-containing nonapeptide has a heptapeptide sequence homologous to a heptapeptide sequence in a cysteine containing decapeptide from the tryptophanyl-tRNA synthetase of human placenta. The nonapeptide appears to bear the thiol group required for enzyme activity.

Amino Acids↗

Subunit dissociation and unfolding of macrophage NO synthase: relationship between enzyme structure, prosthetic group binding, and catalytic function.

Macrophage NO synthase is a homodimer of 130 kDa subunits. Each subunit contains an oxygenase domain that binds iron protoporphyrin IX (heme) and tetrahydrobiopterin (H4biopterin) and a reductase domain that binds FAD, FMN, and calmodulin (CaM) [Ghosh & Stuehr (1995) Biochemistry 34, 801-807]. We have studied the dissociation and unfolding reactions of dimeric iNOS in urea to learn how enzyme structure relates to catalysis and prosthetic group binding. The iNOS dimer dissociated between 0 and 2.5 M urea, and the subunits partially unfolded at 2.5 M urea and above. Dimer dissociation was accompanied by loss of NO synthesis activity and release of bound H4biopterin from the protein. However, the dissociated subunits maintained their cytochrome c and ferricyanide reductase activities and retained near stoichiometric quantities of bound heme. The subunit unfolding transition was accompanied by loss of reductase activities and partial loss of bound heme but retention of bound flavins and CaM. The heme iron in the dissociated subunits remained coordinated through axial cysteine thiolate ligation. Kinetic analysis of dimer dissociation showed that loss of NO synthesis correlated with a loss of heme Soret absorbance at 398 nm and an appearance of absorbance bands at 377 and 460 nm, which were attributed to DTT coordination to the sixth position of the heme iron to form a mixed bisthiolate complex. Subunits could reassociate into a dimer when incubated with L-arginine and H4biopterin. Dimer formation correlated with proportional recoveries of NO synthesis and heme Soret absorbance at 398 nm. Thus, dimeric iNOS undergoes separate dissociation and unfolding transitions in urea, and each transition is accompanied by a loss of a specific catalytic function.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Oxidoreductases↗

[Self-treatment instruction of patients with type 1 diabetes. Report from hospitals belonging to Working Group for Structured Diabetes Therapy (ASD) in Germany 1998].

AIM: Intensified insulin therapy is the therapy of choice for patients with diabetes Type I. Intensified insulin therapy includes an basis-bolus insulin injection regimen or continuous subcutaneous insulin infusion, several times daily blood glucose self-monitoring, self-adaptation of insulin dosages by the patients themselves and a far-reaching liberalization of nutrition. The patients learn self management of diabetes therapy in a structured treatment and teaching program. The effectivity of this program is evaluated in the routine care. PATIENTS AND METHOD: A peer-review quality circle was formed as an official working group of the German Diabetes Association based on the formation of a working group (Arbeitsgemeinschaft für Strukturierte Diabetestherapie [ASD]) of presently 135 general internal medicine departments from city, country and university hospitals throughout the country. The group attempted to document and to improve the quality of structure and process of Type-I diabetes care in its participating institutions by a system of peer supervision. Systematic follow-up examinations of 50 consecutive Type-I diabetic patients 12 to 15 months after participation in the program confirm the outcome quality. The working group meets every year to discuss the results non anonymously. A PC-system (DIQUAL) was developed for collecting, checking and pooling of the outcome data. RESULTS: From 1992 a representative sample of 6.555 patients with Type-I diabetes was examined. At the first time in 1998 the outcome results of 1.789 patients were analyzed depending on the therapeutic goals. In patients with a high initial HbA1c (> or = 8%) an improvement from 9.8 to 8.0% was reached going together with a reduction of severe hypoglycemia from 0.23 to 0.13/patient/year. In patients with an acceptable initial HbA1c (< 8%) the frequency of severe hypoglycemia could be reduced from 0.65 to 0.24/patient/year without any deterioration in metabolic control. Furthermore the incidence of ketoacidosis with hospitalization and the inpatient days were reduced significantly. CONCLUSION: A substantial improvement of HbA1c and reduction of acute complications, especially of severe hypoglycemia in patients with Type-I diabetes were reached by participation in a structured teaching and treatment programme in clinical routine care.

Blood Glucose Self-Monitoring↗

The structure of the cubic coincident site lattice rotation group.

This work is intended to be a mathematical underpinning for the field of grain-boundary engineering and its relatives. The inter-relationships within the set of rotations producing coincident site lattices in cubic crystals are examined in detail. Besides combining previously established but widely scattered results into a unified context, the present work details newly developed representations of the group structure in terms of strings of generators (based on quaternionic number theory, and including uniqueness proofs and rules for algebraic manipulation) as well as an easily visualized topological network model. Important results that were previously obscure or not universally understood (e.g. the Sigma combination rule governing triple junctions) are clarified in these frameworks. The methods also facilitate several general observations, including the very different natures of twin-limited structures in two and three dimensions, the inadequacy of the Sigma combination rule to determine valid quadruple nodes, and a curious link between allowable grain-boundary assignments and the four-color map theorem. This kind of understanding is essential to the generation of realistic statistical models of grain-boundary networks (particularly in twin-dominated systems) and is especially applicable to the field of grain-boundary engineering.

Journal Article↗

Localization of the human Rh blood group gene structure to chromosome region 1p34.3-1p36.1 by in situ hybridization.

A cDNA clone, RhIXb (1384 bp), encoding the entire protein sequence of a human blood group Rh polypeptide has been used to map the Rh locus, by in situ hybridization, to the region p34.3-p36.1 of chromosome 1. Two other unrelated cDNA clones, pUCA2 (750 bp) and pUCIII (1600 bp), isolated during the cloning procedure of the Rh cDNA were investigated simultaneously, and assigned to chromosome 3p21.1-3p22 (clone pUCA2) and to chromosome 22q12.1-22q13.1 (clone pUCIII).

Chromosome Banding↗

Two-dimensional liquid chromatography normal-phase and reversed-phase separation of (co)oligomers.

Many samples contain compounds with various numbers of two or more regular structural groups. Such "multidimensional" samples (according to the Giddings' notation) are best separated in orthogonal chromatographic systems with different selectivities for the individual repeat structural groups, described by separation factors. Correlations between the repeat group selectivities characterize the degree of orthogonality and suitability of chromatographic systems for two-dimensional (2D) separations of two-dimensional samples. The range of the structural units in that can be resolved in a given time can be predicted on the basis of a model describing the repeat group selectivity in the first- and second-dimension systems. Two-dimensional liquid chromatographic system combining reversed-phase (RP) mode in the first dimension and normal-phase (NP) mode in the second dimension were studied with respect to the possibilities of in-line fraction transfer between the two modes. Hydrophilic interaction liquid chromatography (HILIC) with an aminopropyl silica column (APS) is more resistant than classical non-aqueous NP systems against adsorbent desactivation with aqueous solvents transferred in the fractions from the first, RP dimension to the second dimension. Hence, HILIC is useful as a second-dimension separation system for comprehensive RP-NP LCxLC. A comprehensive 2D RP-NP HPLC method was developed for comprehensive 2D separation of ethylene oxide-propylene oxide (EO-PO) (co)oligomers. The first-dimension RP system employed a 120 min gradient of acetonitrile in water on a C18 microbore column at the flow-rate of 10 microL/min. In the second dimension, isocratic HILIC NP with ethanol-dichloromethane-water mobile phase on an aminopropyl silica column at 0.5 mL/min was used. Ten microliter fractions were transferred from the RP to the HILIC NP system at 1 min switching valve cycle frequency.

Acetonitriles↗

Infants use meter to categorize rhythms and melodies: implications for musical structure learning.

Little is known about whether infants perceive meter, the underlying temporal structure of music. We employed a habituation paradigm to examine whether 7-month-old infants could categorize rhythmic and melodic patterns on the basis of the underlying meter, which was implied from event and accent frequency of occurrence. In Experiment 1, infants discriminated duple and triple classes of rhythm on the basis of implied meter. Experiment 2 replicated this result while controlling for rhythmic grouping structure, confirming that infants perceived metrical structure despite occasional ambiguities and conflicting group structure. In Experiment 3, infants categorized melodies on the basis of contingencies between metrical position and pitch. Infants presented with metrical melodies detected reversals of pitch/meter contingencies, while infants presented with non-metrical melodies showed no preference. Results indicate that infants can infer meter from rhythmic patterns, and that they may use this metrical structure to bootstrap their knowledge acquisition in music learning.

Analysis of Variance↗

Chain termination in polyhydroxyalkanoate synthesis: involvement of exogenous hydroxy-compounds as chain transfer agents.

We have identified a range of compounds which, when present during poly(3-hydroxybutyrate) [P(3HB)] accumulation by Ralstonia eutropha (reclassified from Alcaligenes eutrophus), can act as chain transfer agents in the chain termination step of polymerization. End-group analysis by 31P NMR of polymer derivatized with 2-chloro-4,4,5,5-tetramethyl-1,3,2-dioxaphospholane revealed that all these compounds were covalently linked to P(3HB) at the carboxyl terminus. All chain transfer agents possessed one or more hydroxyl groups, and glycerol was selected for further investigation. The number-average molecular mass (Mn) of P(3HB) produced by R. eutropha from glycerol was substantially lower than for polymer produced from glucose, and we identified two new end-group structures. These were attributed to a glycerol molecule bound to the P(3HB) chain via the primary or secondary hydroxyl groups. When a primary hydroxyl group of glycerol is involved in chain transfer, the end-group structure is in both [R] and [S] configurations, implying that chain transfer to glycerol is a random transesterification and that PHA synthase does not catalyse chain transfer. 3-Hydroxybutyric acid is the most probable chain transfer agent in vivo, with propagation and termination reactions involving transfer of the P(3HB) chain to enzyme-bound and free 3-hydroxybutyrate, respectively. Only carboxyl end-groups were detected in P(3HB) extracted from exponentially growing bacteria. It is proposed that a compound other than 3-hydroxybutyryl-CoA acts as a primer in the initiation of polymer synthesis.

Alcaligenes↗

Effect of harvesting the hamstrings tendon for anterior cruciate ligament reconstruction on the morphology and movement of the hamstrings muscle: a novel MRI technique.

This study evaluated intramuscular movement of hamstrings muscle after reconstruction of the ACL with a hamstrings tendon graft. The movement of the muscles during knee flexion was measured using a novel MRI technique called the "tagging snapshot" technique, which labels multiple tagging bands within the musculature. Eleven patients who underwent ACL reconstruction using autogenous semitendinosus and gracilis tendons were studied. The difference in the maximum active knee flexion angle between the ACL-reconstructed and the intact knee was calculated as knee flexion lag. Knee flexion strength was measured in 8 of the 11 patients. The semitendinosus muscle of the ACL-reconstructed knee exhibited three different morphological patterns; group I, similar shape to the intact knee with distal tendonlike structures; group II, smaller proximally than the intact knee with distal tendonlike structures; and group III, considerably smaller proximally than the intact knee without distal tendonlike structures. Each group was associated with a different knee flexion lag and different knee flexion strength. Our results indicated that the effect of hamstrings tendon harvest on knee function is not uniform.

Adult↗