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PubMedDate not supplied

Factors associated with psychotropic drug usage among nursing home residents with dementia.

BACKGROUND: Although federal regulations hold nursing homes responsible for monitoring psychotropic drug (PD) usage, there is a high prevalence of PD usage and significant variation in use across nursing homes. OBJECTIVES: The aims of study were to (a) describe current PD usage in nursing homes and (b) examine resident and nursing home factors associated with PD usage in nursing home residents with dementia. METHODS: A multivariate, multisite, cross-sectional descriptive study was used on data from 107 dementia patients residing in nine randomly selected nursing homes in southeastern Michigan. The PD usage of interest included antipsychotics, antidepressants, anxiolytics or sedatives, and mood stabilizers. Regression analysis tested resident factors, including cognitive ability, functional ability, presence of depressive symptoms, and demographic characteristics, and three facility factors (nursing home size, type of ownership, and level of registered nurse [RN] staffing) in comparison with PD usage. RESULTS: In this study, 67.3% of the participants received at least one PD. The most frequently prescribed PDs were antidepressants (41.1%) and antipsychotics (37.4%). Newly developed antipsychotics such as risperidone were given more frequently to residents than were conventional drugs such as haloperidol. Regression analysis suggests that the presence of depressive symptoms (odds ratio [OR]= 3.5, p < .01) and low levels of RN staffing (OR = 1.0, p < .01) were associated with the use of PD. DISCUSSION: Psychotropic drugs are prescribed frequently for nursing home residents, although such usage is variable. Behavioral symptoms were not an independent predictive factor for PD use. Rather, combined resident and facility characteristics best predicted the use of PDs in nursing home residents. The evaluation of nursing home systems for these characteristics as predictive factors for PD usage in nursing home patients with dementia is suggested by the results. Likewise, attention to new drugs such as selective serotonin reuptake inhibitors and their appropriate use is recommended.

Aged↗
PubMed1996

Costs of HIV+/AIDS at CD4+ counts disease stages based on treatment protocols.

We report treatment protocols for HIV+/AIDS patients by CD4+ counts (T-lymphocyte cells/mm3: > or = 500, 499-200, 199-50, and < 50) as a tool to provide better definition and to project annual costs (total charges for services) and lifetimes costs for HIV+/AIDS. The treatment protocols, derived from the literature and an HIV+/AIDS Physician Panel, defined the resource use associated with antiretroviral therapy and opportunistic disease prophylaxis and treatment. Resource use costs were derived from the published literature, insurance database, Medicare fee schedules, surveys, and the Physician Panel. At CD4+ counts, the rates of opportunistic diseases were derived from the Physician Panel experience; the mean occupancy times were derived from the literature. The sensitivity analysis indicated stability of the lifetime costs to variation in mean occupancy times, rates of opportunistic diseases, rates of adverse events (AE), and costs. The total annual costs (1995 dollars) of HIV+/AIDS patients ranged from $1,934 (> or = 500), $6,015 (200-499), and $9,031 (50-199), to $25,239 ( < 50). The annual costs of opportunistic diseases are esophageal candidiasis (EC) ($2,194), tuberculosis (TB) ($2,924), cryptococcal meningitis (CM) ($17,264), toxoplasmosis ($17,631), Mycobacterium avium complex (MAC) (+20,153), Non-Hodgkin's lymphoma (NHL) ($22,329), wasting syndrome ($26,676), central nervous system (CNS) lymphoma ($27,333), Pneumocystis carinii pneumonia (PCP) [mild ($3,545), moderate ($4,889), and severe ($32,609)], Kaposi' sarcoma (KS) [mild/moderate ($5,902), and severe ($10,744)], and cytomegalovirus (CMV) retinitis ($100,337). The projected lifetime costs of HIV+/AIDS are $94,726 (annual costs $7,645). Our lower lifetime costs as compared with recent estimates may be due to including resources only for HIV+/AIDS-related treatment and not for non-HIV+/AIDS conditions, as well as reduced resource use resulting from more efficient diagnostic and therapeutic techniques and earlier prophylaxis provided by experienced HIV+/AIDS physicians. Nonetheless, our estimates are consistent with decreasing costs of HIV+/AIDS due to a reduction in the average length of stay and frequency of hospitalizations as well as to replacement of inpatient care by outpatient services.

AIDS-Related Opportunistic Infections↗
PubMed2005

Determinants of mycophenolic acid levels after renal transplantation.

There are data suggesting an association between mycophenolic acid (MPA) levels and acute rejection and toxicity in renal transplant recipients treated with mycophenolate mofetil (MMF), and therefore, knowledge of factors determining MPA levels may aid in accurate adjustment of MMF dosage. A total of 4970 samples taken 12 hours postdose were analyzed for MPA by immunoassay at regular intervals from the first week posttransplantation in 117 renal transplant patients immunosuppressed with MMF and tacrolimus in a steroid-sparing regimen (prednisolone for the first 7 days only). MPA levels rose in the first 3 months and stabilized thereafter; dose-normalized MPA levels rose throughout the first 12 months and subsequently stabilized. Multivariate analysis by means of a population-averaged linear regression showed positive associations between MPA level and total daily dose (P < 0.001) but not individual dose or total daily dose corrected for body weight. Positive associations were also seen with serum albumin (P = 0.01), tacrolimus trough level (P = 0.01), and female gender (P = 0.002). The association with tacrolimus levels diminished with time. Negative associations were seen between MPA level and higher estimated creatinine clearance (P < 0.001), and also with increasing alanine transaminase levels (P = 0.002), the use of oral antibiotics (P < 0.001), and infective diarrhea (P < 0.001). The latter findings may be related to changes in enterohepatic recirculation of MPA. Many clinical variables show associations with trough MPA levels. An understanding of these factors may aid therapeutic monitoring of MMF.

Adult↗
PubMed1995

G1 cyclin turnover and nutrient uptake are controlled by a common pathway in yeast.

Entry into a new cell cycle is triggered by environmental signals at a point called Start in G1 phase. A key regulator of this transition step in yeast is the CDC28 kinase together with its short-lived regulatory subunits called G1-cyclins or CLN proteins. To identify genes involved in G1-cyclin degradation, we employed a genetic screen by selecting for stable CLN1-beta-galactosidase fusion proteins. Surprisingly, one group of mutants was found to be allelic to GRR1, a gene previously described to be involved in glucose uptake, glucose repression, and divalent cation transport. In grr1 mutants, both CLN1 and CLN2 cyclins are significantly stabilized. A suppressor analysis indicated that G1-cyclin stabilization in grr1 was not a consequence of the nutrient uptake defect. This suggests that the GRR1 gene product is part of a common regulatory pathway linking two functions important for cell growth, nutrient uptake, and G1 cyclin-controlled cell division.

Biological Transport↗
PubMed2001

Partial synchronization and spontaneous spatial ordering in coupled chaotic systems.

A model of many symmetrically and locally coupled chaotic oscillators is studied. Partial chaotic synchronizations associated with spontaneous spatial ordering are demonstrated. Very rich patterns of the system are revealed, based on partial synchronization analysis. The stabilities of different partially synchronous spatiotemporal structures and some dynamical behaviors of these states are discussed both numerically and analytically.

Journal Article↗
PubMed2004

Design and robustness of delayed feedback controllers for discrete systems.

We study a matrix form of time-delay feedback control in the context of discrete time maps of high dimension. In almost all cases where standard proportional feedback control methods can achieve control, time-delay feedback controllers containing only static elements can be designed to achieve identical linear stability properties. Analysis of an example involving a ring of coupled maps that can be controlled at only two sites demonstrates that the time-delay controller equivalent to a standard optimal controller can be equally robust in the presence of noise, except at special points in parameter space where the uncontrolled system has a mode with Floquet multiplier exactly equal to 1. Numerical simulations confirm the results of the analysis.

Journal Article↗
PubMed2004

Entropy-induced microphase separation in hard diblock copolymers.

Whereas entropy can induce phase behavior that is as rich as seen in energetic systems, microphase separation remains a very rare phenomenon in entropic systems. In this paper, we present a density functional approach to study the possibility of entropy-driven microphase separation in diblock copolymers. Our model system consists of copolymers composed of freely jointed slender hard rods. The two types of monomeric segments have comparable lengths, but a significantly different diameter, the latter difference providing the driving force for the phase separation. At the same time this system can also exhibit liquid crystalline phases. We treat this system in the appropriate generalization of the Onsager approximation to chain-like particles. Using a linear stability (bifurcation) analysis, we analytically determine the onset of the microseparated and the nematic phases for long chains. We find that for very long chains the microseparated phase always pre-empts the nematic. In the limit of infinitely long chains, the correlations within the chain become Gaussian and the approach becomes exact. This allows us to define a Gaussian limit in which the theory strongly simplifies and the competition between microphase separation and liquid crystal formation can be studied essentially analytically. Our main results are phase diagrams as a function of the remaining model parameters: i.e., the diameter ratio, the length ratio, and the number ratio of the two types of segments. We also determine the amplitude of the inhomogeneous order as a function of position along the chain at the onset of the microphase separation instability. Finally, we give suggestions as to how this type of entropy-induced microphase separation could be observed experimentally.

Journal Article↗
PubMed2004

Synchronization in coupled chaotic oscillators with a no-flux boundary condition.

We investigate the synchronization of coupled chaotic oscillators with a no-flux boundary condition. We find that the spectrum of the coupling matrix is divided into two parts, the isolated part with a zero eigenvalue and the continuous one with the other N-1 eigenvalues falling onto a line. Based on the eigenvalue analysis, the stability of the synchronization in a coupled Lorenz system is explored thoroughly in the parameter space of the size of the system, the diffusion, and gradient coupling constants.

Journal Article↗
PubMed2001

Functional studies of Ycf3: its role in assembly of photosystem I and interactions with some of its subunits.

The Ycf3 protein is essential for the accumulation of the photosystem I (PSI) complex and acts at a post-translational level. The sequence of Ycf3 is conserved in cyanobacteria, algae, and plants and contains three tetratrico-peptide repeats (TPR). TPRs have been shown to function as sites for protein-protein interactions. The mutations Y95A/Y96A and Y142A/W143A in the second and third TPR repeats lead to a modest decrease of PSI, but they prevent photoautotrophic growth and cause enhanced light sensitivity even though the accumulated PSI complex is fully functional. This phenotype can be reversed under anaerobic conditions and appears to be the result of photooxidative damage. A temperature-sensitive ycf3 mutant, generated by random mutagenesis of a conserved region near the N-terminal end of Ycf3, was used in temperature-shift experiments to show that Ycf3 is required for PSI assembly but not for its stability. Immunoblot analysis of thylakoid membranes separated by two-dimensional gel electrophoresis and immunoprecipitations shows that Ycf3 interacts directly with the PSI subunits PsaA and PsaD, but not with subunits from other photosynthetic complexes. Thus, Ycf3 appears to act as a chaperone that interacts directly and specifically with at least two of the PSI subunits during assembly of the PSI complex.

Aerobiosis↗
PubMed2004

A new mobile robot control approach via fusion of control signals.

This paper proposes an alternative approach to address the problem of coordinating behaviors in mobile robot navigation: fusion of control signals. Such approach is based on a set of two decentralized information filters, which accomplish the data fusion involved. Besides these two fusion engines, control architectures designed according to this approach also embed a set of different controllers that generate reference signals for the robot linear and angular speeds. Such signals are delivered to the two decentralized information filters, which estimate suitable overall reference signals for the robot linear and angular speeds, respectively. Thus, the background for designing such control architectures is provided by the nonlinear systems theory, which makes this approach different from any other yet proposed. This background also allows checking control architectures designed according to the proposed approach for stability. Such analysis is carried out in the paper, and shows that the robot always reaches its final destination, in spite of either obstacles along its path or the environment layout. As an example, a control architecture is designed to guide a mobile robot in an experiment, whose results allows checking the good performance of the control architecture and validating the design approach proposed as well.

Algorithms↗
PubMed2006

Trajectory tracking of piezoelectric positioning stages using a dynamic sliding-mode control.

Trajectory tracking performance of a piezoelectric positioning stage almost depends on whether the tracking controller can effectively compensate the inherent hysteresis phenomenon. In this paper, a dynamic sliding-mode control (DSMC) with backstepping is proposed for the trajectory tracking of the piezoelectric positioning stage, which is suitable for a component of scanning microscopes. An equivalent model developed from a linear motion dynamics with addition of the hysteresis nonlinearity and strain-dependent function first is proposed to approximately represent the dynamics of motion of a one-dimensional piezoelectric positioning stage. Then, based on the equivalent model, the DSMC with an asymptotical sliding surface is proposed for the trajectory tracking control of the piezoelectric positioning stage. Moreover, the analysis of stability can be completed by mathematics, and the convergence rate of the tracking error can be governed by the choice of the control parameter values. Using the DSMC to trajectory tracking control, the piezoelectric positioning stage becomes more suitable for practical applications, especially with the need of various trajectories tracking in microscopy. To validate the proposed control scheme, a computer-based controller and a piezoelectric positioning stage with a capacitive displacement sensor are implemented. Experimental results illustrate the feasibility of the proposed controller for trajectory tracking applications.

Journal Article↗
PubMed2006

Crystal structural analysis and metal-dependent stability and activity studies of the ColE7 endonuclease domain in complex with DNA/Zn2+ or inhibitor/Ni2+.

The nuclease domain of ColE7 (N-ColE7) contains an H-N-H motif that folds in a beta beta alpha-metal topology. Here we report the crystal structures of a Zn2+-bound N-ColE7 (H545E mutant) in complex with a 12-bp duplex DNA and a Ni2+-bound N-ColE7 in complex with the inhibitor Im7 at a resolution of 2.5 A and 2.0 A, respectively. Metal-dependent cleavage assays showed that N-ColE7 cleaves double-stranded DNA with a single metal ion cofactor, Ni2+, Mg2+, Mn2+, and Zn2+. ColE7 purified from Escherichia coli contains an endogenous zinc ion that was not replaced by Mg2+ at concentrations of <25 mM, indicating that zinc is the physiologically relevant metal ion in N-ColE7 in host E. coli. In the crystal structure of N-ColE7/DNA complex, the zinc ion is directly coordinated to three histidines and the DNA scissile phosphate in a tetrahedral geometry. In contrast, Ni2+ is bound in N-ColE7 in two different modes, to four ligands (three histidines and one phosphate ion), or to five ligands with an additional water molecule. These data suggest that the divalent metal ion in the His-metal finger motif can be coordinated to six ligands, such as Mg2+ in I-PpoI, Serratia nuclease and Vvn, five ligands or four ligands, such as Ni2+ or Zn2+ in ColE7. Universally, the metal ion in the His-metal finger motif is bound to the DNA scissile phosphate and serves three roles during hydrolysis: polarization of the P-O bond for nucleophilic attack, stabilization of the phosphoanion transition state and stabilization of the cleaved product.

Amino Acid Motifs↗
PubMed2001

Amino-acid substitutions at the fully exposed P1 site of bovine pancreatic trypsin inhibitor affect its stability.

It is widely accepted that solvent-exposed sites in proteins play only a negligible role in determining protein energetics. In this paper we show that amino acid substitutions at the fully exposed Lys15 in bovine pancreatic trypsin inhibitor (BPTI) influenced the CD- and DSC-monitored stability: The T(den) difference between the least (P1 Trp) and the most stable (P1 His) mutant is 11.2 degrees C at pH 2.0. The DeltaH(den) versus T(den) plot for all the variants at three pH values (2.0, 2.5, 3.0) is linear (DeltaC(p,den) = 0.41 kcal* mole(-1) * K(-1); 1 cal = 4.18 J) leading to a DeltaG(den) difference of 2.1 kcal*mole(-1). Thermal denaturation of the variants monitored by CD signal at pH 2.0 in the presence of 6 M GdmCl again showed differences in their stability, albeit somewhat smaller (DeltaT(den) =7.1 degrees C). Selective reduction of the Cys14-Cys 38 disulfide bond, which is located in the vicinity of the P1 position did not eliminate the stability differences. A correlation analysis of the P1 stability with different properties of amino acids suggests that two mechanisms may be responsible for the observed stability differences: the reverse hydrophobic effect and amino acid propensities to occur in nonoptimal dihedral angles adopted by the P1 position. The former effect operates at the denatured state level and causes a drop in protein stability for hydrophobic side chains, due to their decreased exposure upon denaturation. The latter factor influences the native state energetics and results from intrinsic properties of amino acids in a way similar to those observed for secondary structure propensities. In conclusion, our results suggest that the protein-stability-derived secondary structure propensity scales should be taken with more caution.

Amino Acid Substitution↗
PubMed1994

Triple-helix formation interferes with the transcription and hinged DNA structure of the interferon-inducible 6-16 gene promoter.

The interferon responsive element (IRE) of the 6-16 gene lies within two 39-bp elements in tandem. A purine-rich oligodeoxynucleotide, oligo(dN), was found to be able to pair with the purine-rich strand of the IRE in an antiparallel orientation which led to triple-helix formation with Mg2+ being necessary for triplex stability. Footprinting analysis confirmed these results. The interaction between the IRE and the oligo(dN) was reversible and had a Kd equal to 20 nM. The two repeats of the 6-16 gene IRE can form a hinged DNA structure through pairing of their purine-rich regions; exonuclease III experiments support this model. The hybrid DNA structure leads to a parallel pairing of the purine strands of the 6-16 gene IRE and this conformation was shown to be destabilized by triplex formation. When co-transfected with a reporter gene whose promoter was under the control of the 6-16 gene IRE, the triple-helix-forming oligo(dN)s inhibit the interferon-induced stimulation of the reporter gene with complete inhibition being obtained with 1 microM oligo(dN) at the time of transfection. When added to the cell culture medium after transfection, the concentrations of oligo(dN) needed to obtain 50% inhibition of the interferon effect on gene transcription must be 50-100 times higher. Besides the existence of a peculiar structure for the 6-16 gene IRE, the possibility of interfering with gene expression by means of oligo(dN)s is demonstrated.

Base Sequence↗
PubMed1995

Involvement of the C-terminal tail in the activity of Drosophila alcohol dehydrogenase. Evaluation of truncated proteins constructed by site-directed mutagenesis.

Drosophila alcohol dehydrogenase belongs to the heterogeneous family of short-chain dehydrogenases/reductases, which does not include the well characterized mammalian alcohol dehydrogenases. Although it is clear that the main biological role of this enzyme is in alcohol oxidation, in the absence of the three-dimensional conformation only partial information on the protein regions involved in the active site, and the coenzyme and substrate interacting cavities is available. Two segments have already been identified, a coenzyme-binding segment at the N-terminus, and the reactive Tyr152 and Lys156 residues. Limited proteolytic assays had suggested the involvement of the 13 C-terminal amino acids in the function of the enzyme. By site-directed mutagenesis, we have constructed eight different truncated mutant enzymes and expressed them in Escherichia coli. The purified mutant enzymes have been recovered and characterized using monoclonal antibodies. Kinetic analysis and stability assays have been performed, and clearly demonstrate the contribution of the last 13 amino acids to the activity. We hypothesize that the C-terminal tail constitutes an essential region for maintaining the hydrophobicity of the catalytic pocket needed for binding of the substrate.

Alcohol Dehydrogenase↗
PubMed2004

Thermodynamic analysis of the unfolding and stability of the dimeric DNA-binding protein HU from the hyperthermophilic eubacterium Thermotoga maritima and its E34D mutant.

We have studied the stability of the histone-like, DNA-binding protein HU from the hyperthermophilic eubacterium Thermotoga maritima and its E34D mutant by differential scanning microcalorimetry and CD under acidic conditions at various concentrations within the range of 2-225 micro m of monomer. The thermal unfolding of both proteins is highly reversible and clearly follows a two-state dissociation/unfolding model from the folded, dimeric state to the unfolded, monomeric one. The unfolding enthalpy is very low even when taking into account that the two disordered DNA-binding arms probably do not contribute to the cooperative unfolding, whereas the quite small value for the unfolding heat capacity change (3.7 kJ.K(-1).mol(-1)) stabilizes the protein within a broad temperature range, as shown by the stability curves (Gibbs energy functions vs. temperature), even though the Gibbs energy of unfolding is not very high either. The protein is stable at pH 4.00 and 3.75, but becomes considerably less so at pH 3.50 and below, to the point that a simple decrease in concentration will lead to unfolding of both the wild-type and the mutant protein at pH 3.50 and low temperatures. This indicates that various acid residues lose their charges leaving uncompensated positively charged clusters. The wild-type protein is more stable than its E34D mutant, particularly at pH 4.00 and 3.75 although less so at 3.50 (1.8, 1.6 and 0.6 kJ.mol(-1) at 25 degrees C for DeltaDeltaG at pH 4.00, 3.75 and 3.50, respectively), which seems to be related to the effect of a salt bridge between E34 and K13.

Amino Acid Sequence↗
PubMed1990

Evidence for vasoactive intestinal peptide as a mediator of non-adrenergic non-cholinergic neurotransmission in the trachea.

1. The tracheal pouch, a surgical preparation designed to demonstrate non-adrenergic non-cholinergic inhibition, was prepared in chloralose/urethane-anaesthetized and positively ventilated guinea-pigs. The animals were given atropine and propranolol intraperitoneally to block cholinergic and adrenergic divisions of the autonomic innervation. The cervical vagi and sympathetic trunks were isolated bilaterally and cut cranially. 2. The relaxation responses of the pouch to graded concentrations of VIP (10(-11) M to 10(-6) M) were determined. Two consecutive dose-response curves at 20 min apart were determined in the control group. The VIP dose-response curves in the control group were reproducible and failed to show statistical significance upon paired Student's t-test. 3. [Ac-Tyr1,D-Phe2]-GRF(1-29)-amide, a VIP antagonist hereby referred to as antagonist-1 was tested for its ability to inhibit the VIP-induced pouch relaxation. Separate groups of animals were used for each concentration (10(-8) M, 10(-6) M or 10(-5) M) of the antagonist. VIP dose-response curves were determined before and after the pouch was incubated with the antagonist for 10 min. The second curve was determined after rinsing the pouch gently with saline and allowing 5 min for the pouch to stabilize. Statistical analysis showed that only 10(-5) M of the antagonist significantly blocked the VIP-induced tracheal pouch relaxation. 4. [4-C1-D-Phe6,Leu17]-VIP, another VIP antagonist hereby referred to as antagonist-2 was tested similarly for its ability to block the VIP-induced pouch relaxation. The significant blockade of the VIP-induced pouch relaxation was obtained with this antagonist at a concentration of 10(-6) M.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗