35 research outputs found
Large Deviations for Stochastic Nematic Liquid Crystals driven by Multiplicative Gaussian Noise
We study a stochastic two-dimensional nematic liquid crystal model with multiplicative Gaussian noise. We prove the Wentzell-Freidlin type large deviations principle for the small noise asymptotic of solutions using weak convergence metho
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Examining the effects of sodium ions on the binding of antagonists to dopamine D2 and D3 receptors
Many G protein-coupled receptors have been shown to be sensitive to the presence of sodium ions (Na+). Using radioligand competition binding assays, we have examined and compared the effects of sodium ions on the binding affinities of a number of structurally diverse ligands at human dopamine D2 and dopamine D3 receptor subtypes, which are important therapeutic targets for the treatment of psychotic disorders. At both receptors, the binding affinities of the antagonists/inverse agonists SB-277011-A, L,741,626, GR 103691 and U 99194 were higher in the presence of sodium ions compared to those measured in the presence of the organic cation, N-methyl-D-glucamine, used to control for ionic strength. Conversely, the affinities of spiperone and (+)-butaclamol were unaffected by the presence of sodium ions. Interestingly, the binding of the antagonist/inverse agonist clozapine was affected by changes in ionic strength of the buffer used rather than the presence of specific cations. Similar sensitivities to sodium ions were seen at both receptors, suggesting parallel effects of sodium ion interactions on receptor conformation. However, no clear correlation between ligand characteristics, such as subtype selectivity, and sodium ion sensitivity were observed. Therefore, the properties which determine this sensitivity remain unclear. However these findings do highlight the importance of careful consideration of assay buffer composition for in vitro assays and when comparing data from different studies, and may indicate a further level of control for ligand binding in vivo
Designing clinical trials for assessing the effects of cognitive training and physical activity interventions on cognitive outcomes: The Seniors Health and Activity Research Program Pilot (SHARP-P) Study, a randomized controlled trial
<p>Abstract</p> <p>Background</p> <p>The efficacy of non-pharmacological intervention approaches such as physical activity, strength, and cognitive training for improving brain health has not been established. Before definitive trials are mounted, important design questions on participation/adherence, training and interventions effects must be answered to more fully inform a full-scale trial.</p> <p>Methods</p> <p>SHARP-P was a single-blinded randomized controlled pilot trial of a 4-month physical activity training intervention (PA) and/or cognitive training intervention (CT) in a 2 × 2 factorial design with a health education control condition in 73 community-dwelling persons, aged 70-85 years, who were at risk for cognitive decline but did not have mild cognitive impairment.</p> <p>Results</p> <p>Intervention attendance rates were higher in the CT and PACT groups: CT: 96%, PA: 76%, PACT: 90% (p=0.004), the interventions produced marked changes in cognitive and physical performance measures (p≤0.05), and retention rates exceeded 90%. There were no statistically significant differences in 4-month changes in composite scores of cognitive, executive, and episodic memory function among arms. Four-month improvements in the composite measure increased with age among participants assigned to physical activity training but decreased with age for other participants (intervention*age interaction p = 0.01). Depending on the choice of outcome, two-armed full-scale trials may require fewer than 1,000 participants (continuous outcome) or 2,000 participants (categorical outcome).</p> <p>Conclusions</p> <p>Good levels of participation, adherence, and retention appear to be achievable for participants through age 85 years. Care should be taken to ensure that an attention control condition does not attenuate intervention effects. Depending on the choice of outcome measures, the necessary sample sizes to conduct four-year trials appear to be feasible.</p> <p>Trial Registration</p> <p>Clinicaltrials.gov Identifier: <a href="http://www.clinicaltrials.gov/ct2/show/NCT00688155">NCT00688155</a></p
Derivation of Plate and Rod Equations for a Piezoelectric Body from a Mixed Three-Dimensional Variational Principle
From garden to store: local perspectives of changing food and nutrition security in a Pacific Island country
The action of a negative allosteric modulator at the dopamine D2 receptor is dependent upon sodium ions
Induced effects of sodium ions on dopaminergic G-protein coupled receptors
G-protein coupled receptors, the largest family of proteins in the human genome, are involved in many complex signal transduction pathways, typically activated by orthosteric ligand binding and subject to allosteric modulation. Dopaminergic receptors, belonging to the class A family of G-protein coupled receptors, are known to be modulated by sodium ions from an allosteric binding site, although the details of sodium effects on the receptor have not yet been described. In an effort to understand these effects, we performed microsecond scale all-atom molecular dynamics simulations on the dopaminergic D2 receptor, finding that sodium ions enter the receptor from the extracellular side and bind at a deep allosteric site (Asp2.50). Remarkably, the presence of a sodium ion at this allosteric site induces a conformational change of the rotamer toggle switch Trp6.48 which locks in a conformation identical to the one found in the partially inactive state of the crystallized human β2 adrenergic receptor. This study provides detailed quantitative information about binding of sodium ions in the D2 receptor and reports a possibly important sodium-induced conformational change for modulation of D2 receptor function.We acknowledge partial support from the EU funded VPH Network of Excellence, La MARATO de TV3 Foundation (Ref.-No. 091010), the HERACLES (RD06/0009) and COMBIOMED (RD07/0067), the Spanish Ministerio de Educacion y Ciencia (SAF2009-13609-C04-04). GDF acknowledges support from the Ramon y Cajal scheme and by the Spanish Ministry of Science and Innovation (Ref. FIS2008-01040). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscrip
Long-term outcomes of 1326 laparoscopic incisional and ventral hernia repair with the routine suturing concept: a single institution experience
Purpose: This retrospective chart analysis reports and assesses the long-term (beyond 10 years) safety and efficiency of a single institution’s experience in 1326 laparoscopic incisional and ventral hernia repairs (LIVHR), defending the principle of the suturing defect (augmentation repair concept) prior to laparoscopic reinforcement with a composite mesh (IPOM Plus). This study aims to prove the feasibility and validity of IPOM Plus repair, among other concepts, as a well-justified treatment of incisional or ventral hernias, rendering a good long-term outcome result. Methods: A single institution’s systematic retrospective review of 1326 LIVHR was conducted between the years 2000 and 2014. A standardized technique of routine closure of the defect prior to the intraperitoneal onlay mesh (IPOM) reinforcement was performed in all patients. The standardized technique of “defect closure” by laparoscopy approximating the linea alba under physiological tension was assigned by either the transparietal U reverse interrupted stitches or the extracorporeal closure in larger defects. All patients benefited from the implant Parietex composite® mesh through an Intraperitoneal Onlay Mesh placement with transfacial suturing. Results: LIVHR was performed on 1326 patients, 52.57 % female and 47.43 % male. The majority of our patients were young (mean age 52.19 years) and obese (average BMI 32.57 kg/m2). The mean operating time was 70 min and hospital stay 2 days, with a mean follow-up of 78 months. On the overall early complications of 5.78 %, we achieved over time the elimination of the dead space by routine closure of the defect, thus reducing seroma formation to 2.56 %, with a low risk of infection <1 %. Post-op sepsis occurred in only nine cases. Three secondary serosal breakdowns and two late perforations were re-operated, and three diabetic patients had infected hematomas, necessitating mesh removal. Through technical improvement in the suturing concept and our growing experience, we managed to reduce the incidence of transient pain to a low acceptable rate of 3.24 % (VAS 5–7) that decreased to 2.56 % on a chronic pain stage, which is comparable to the literature. On the overall rate of late complications of 10.74 %, we noticed also that by reducing the dead space, the chronic pain, skin bulging, and rate of recurrence were reduced to, respectively, 2.56, 1.50, and 4.72 %. One case of mortality was due to a tracheal stenosis, responsible for an acute respiratory syndrome. On a second-look follow-up of 126 patients (9.5 %), 45.23 % were adhesion free, 42.06 % had minor adhesions classified as Müller I, and 12.69 % had serosal adhesions classified as Müller II. Conclusion: Our long series confirms the unexpected high rate of feasibility in the suturing concept or augmentation technique, and confers additional benefits to the conventional advantages of LIVHR in terms of reducing the overall morbidity, with a low rate of recurrences. Based on our experience and study, the current best indications for a successful LIVHR procedure should be tailored upon the limitations of the defect’s width and proper patient selection, to restore adequately the optimal functionality of the abdominal muscles and provide better functional and cosmetic outcomes.SCOPUS: ar.jinfo:eu-repo/semantics/publishe