Efecto de un sistema automático de dispensación de medicamentos sobre el gasto farmacéutico y el grado de satisfacción del usuario

Objective: To evaluate in economic terms, the effect of replacing traditional kits for the implementation of automated dispensing of medications in the Intensive Care Unit. Analyze the degree of acceptance of such changeon the part of users.   Method: For the economic analysis is considered tangible direct and indirect costs resulting from the implementation: initial capital investment, cost of staff involved, the political cost of drug consumption. All these aspects were evaluated before and after implantation. The degree of user satisfaction was assessed using a standardized questionnaire. Results: After the estimation of costs, we found that the expenditure incurred on the initial investment will be quickly offset by the cost mainly referred to the politics of consumption of drugs with a reduction of 24% over the previous delivery system. The cost in personal chapter is also reduced by 11%, and the cost per stay and cost / income fell by 26% and 30% respectively over the previous system. The evaluation questionnaire revealed that users are satisfied with the implementation and 84% of nurses would recommend it to other units. Conclusions: Automated Dispensing Systems Drugs are a new technological tool to control drug spending, with good acceptance by users.Objetivo: Evaluar en términos económicos el efecto de la sustitución de botiquines tradicionales por la implantación de Sistemas Automáticos de Dispensación de Medicamentos en la Unidad de Cuidados Intensivos. Analizar el grado de aceptación de dicho cambio por parte de los usuarios.   Método: Para el análisis económico, se consideraron los costes directos e indirectos tangibles, derivados de la implantación: inversión inicial de capital, coste del personal implicado, coste en política de consumo de medicamentos. Todos estos aspectos se evaluaron antes y después de la implantación. El grado de satisfacción de los usuarios se evaluó a través de un cuestionario estandarizado.   Resultados: Tras la estimación de los costes, comprobamos que el gasto realizado en la inversión inicial se verá rápidamente compensado fundamentalmente por el coste referido a la política de consumos de medicamentos con una reducción del 24% con respecto al sistema de dispensación anterior. El coste en el capitulo de personal también se ve reducido un 11%, así como el coste/estancia y coste/ingreso que disminuyen un 26% y 30% respectivamente en relación al sistema anterior. La evaluación del cuestionario reveló que los usuarios están satisfechos con la implantación y un 84% del personal de enfermería lo recomendaría a otras unidades.   Conclusiones: Los Sistemas Automáticos de Dispensación de Medicamentos constituyen una nueva herramienta tecnológica para el control del gasto farmacéutico, con buena aceptación por parte de los usuario

Optimal transfers from Moon to L2L_2 halo orbit of the Earth-Moon system

In this paper, we seek optimal solutions for a transfer from a parking orbit around the Moon to a halo orbit around $L_2$ of the Earth-Moon system, by applying a single maneuver and exploiting the stable invariant manifold of the hyperbolic parking solution at arrival. For that, we propose an optimization problem considering as variables both the orbital characteristics of a parking solution around the Moon, (namely, its Keplerian elements) and the characteristics of a transfer trajectory guided by the stable manifold of the arrival Halo orbit. The problem is solved by a nonlinear programming method (NLP), aiming to minimize the cost of $\Delta V$ to perform a single maneuver transfer, within the framework of the Earth-Moon system of the circular restricted three-body problem. Results with low $\Delta V$ and suitable time of flight show the feasibility of this kind of transfer for a Cubesat

Numerical investigations of the orbital dynamics around a synchronous binary system of asteroids

In this article, equilibrium points and families of periodic orbits in the vicinity of the collinear equilibrium points of a binary asteroid system are investigated with respect to the angular velocity of the secondary body, the mass ratio of the system and the size of the secondary. We assume that the gravitational fields of the bodies are modeled assuming the primary as a mass point and the secondary as a rotating mass dipole. This model allows to compute families of planar and halo periodic orbits that emanate from the equilibrium points $L_1$ and $L_2$. The stability and bifurcations of these families are analyzed and the results are compared with the results obtained with the Restricted Three-Body Problem (RTBP). The results provide an overview of the dynamical behavior in the vicinity of a binary asteroid system

Analysis of the dynamics of a spacecraft in the vicinity of an asteroid binary system with equal masses

In this work, we performed a dynamical analysis of a spacecraft around a nearly equal-mass binary near-Earth asteroid with application to the asteroid 2017 YE5, which is also a possible dormant Jupiter-family comet. Thus, we investigated the motion of a particle around this binary system using the circular restricted three-body problem. We calculated the locations of the Lagrangian points of the system and their Jacobi constant. Through numerical simulations, using the Poincar\'e Surface of Sections, it was possible to find several prograde and retrograde periodic orbits around each binary system's primary, some exhibiting significantly-sized higher-order behavior. We also calculated the stability of these orbits. After finding the periodic orbits, we investigated the influence of solar radiation pressure on these orbits. For this analysis, we considered that the area-to-mass ratio equals 0.01 and 0.1. We also performed a spacecraft lifetime analysis considering the physical and orbital characteristics of the 2017YE5 system and investigated the behavior of a spacecraft in the vicinity of this system. We analyzed direct and retrograde orbits for different values of Jacobi's constant. This study investigated orbits that survive for at least six months, not colliding or escaping the system during that time. We also analyze the initial conditions that cause the spacecraft to collide with $M_1$ or $M_2$, or escape from the system. In this work, we take into account the gravitational forces of the binary asteroid system and the solar radiation pressure (SRP). Finally, we calculated optimal bi-impulsive orbital maneuvers between the collinear Lagrangian points. We found a family of possible orbital transfers considering times of flight between 0.1 and 1 day

Fertility Control Options for Management of Free-roaming Horse Populations

The management of free-roaming horses (Equus ferus) and burros (E. asinus) in the United States has been referred to as a “wicked problem” because, although there are population control options, societal values will ultimately determine what is acceptable and what is not. In the United States, free-roaming equids are managed by different types of organizations and agencies, and the landscapes that these animals inhabit vary widely in terms of access, size, topography, climate, natural resources, flora, and fauna. This landscape diversity, coupled with contemporary socioeconomic and political environments, means that adaptive management practices are needed to regulate these free-roaming populations. The Bureau of Land Management (BLM) currently manages free-roaming equids on 177 herd management areas in the United States by applying fertility control measures in situ and/or removing horses, which are either adopted by private individuals or sent to long-term holding facilities. The BLM off-range population currently includes \u3e50,000 animals and costs approximately $50 million USD per year to maintain; on-range equid numbers were estimated in March 2022 to be approximately 82,384. On-range populations can grow at 15–20% annually, and current estimates far exceed the designated appropriate management level of 26,715. To reduce population recruitment, managers need better information about effective, long-lasting or permanent fertility control measures. Because mares breed only once a year, fertility control studies take years to complete. Some contraceptive approaches have been studied for decades, and results from various trials can collectively inform future research directions and actions. Employing 1 or more fertility control tools in concert with removals offers the best potential for success. Active, iterative, cooperative, and thoughtful management practices can protect free-roaming horses while simultaneously protecting the habitat. Herein, we review contraceptive vaccines, intrauterine devices, and surgical sterilization options for controlling fertility of free-roaming horses. This review provides managers with a “fertility control toolbox” and guides future research

Reduced Expression of the Vesicular Acetylcholine Transporter and Neurotransmitter Content Affects Synaptic Vesicle Distribution and Shape in Mouse Neuromuscular Junction

In vertebrates, nerve muscle communication is mediated by the release of the neurotransmitter acetylcholine packed inside synaptic vesicles by a specific vesicular acetylcholine transporter (VAChT). Here we used a mouse model (VAChT KDHOM) with 70% reduction in the expression of VAChT to investigate the morphological and functional consequences of a decreased acetylcholine uptake and release in neuromuscular synapses. Upon hypertonic stimulation, VAChT KDHOM mice presented a reduction in the amplitude and frequency of miniature endplate potentials, FM 1-43 staining intensity, total number of synaptic vesicles and altered distribution of vesicles within the synaptic terminal. In contrast, under electrical stimulation or no stimulation, VAChT KDHOM neuromuscular junctions did not differ from WT on total number of vesicles but showed altered distribution. Additionally, motor nerve terminals in VAChT KDHOM exhibited small and flattened synaptic vesicles similar to that observed in WT mice treated with vesamicol that blocks acetylcholine uptake. Based on these results, we propose that decreased VAChT levels affect synaptic vesicle biogenesis and distribution whereas a lower ACh content affects vesicles shape

An Analysis of the Myocardial Transcriptome in a Mouse Model of Cardiac Dysfunction with Decreased Cholinergic Neurotransmission

Autonomic dysfunction is observed in many cardiovascular diseases and contributes to cardiac remodeling and heart disease. We previously reported that a decrease in the expression levels of the vesicular acetylcholine transporter (VAChT) in genetically-modified homozygous mice (VAChT KDHOM) leads to decreased cholinergic tone, autonomic imbalance and a phenotype resembling cardiac dysfunction. In order to further understand the molecular changes resulting from chronic long-term decrease in parasympathetic tone, we undertook a transcriptome-based, microarray-driven approach to analyze gene expression changes in ventricular tissue from VAChT KDHOM mice. We demonstrate that a decrease in cholinergic tone is associated with alterations in gene expression in mutant hearts, which might contribute to increased ROS levels observed in these cardiomyocytes. In contrast, in another model of cardiac remodeling and autonomic imbalance, induced through chronic isoproterenol treatment to increase sympathetic drive, these genes did not appear to be altered in a pattern similar to that observed in VAChT KDHOM hearts. These data suggest the importance of maintaining a fine balance between the two branches of the autonomic nervous system and the significance of absolute levels of cholinergic tone in proper cardiac function

Endotoxin tolerance and cross-tolerance in mast cells involves TLR4, TLR2 and FcεR1 interactions and SOCS expression: perspectives on immunomodulation in infectious and allergic diseases

<p>Abstract</p> <p>Background</p> <p>The study of the endotoxin tolerance phenomenon in light of the recently defined roles of mast cells and toll-like receptors as essential components of the innate immune response and as orchestrators of acquired immunity may reveal potentially useful mechanisms of immunomodulation of infectious and allergic inflammatory responses, such as sepsis or asthma. Here we evaluated the phenomenon of direct tolerance of endotoxins, as well as the induction of cross-tolerance and synergism by stimulation with toll-like receptor-2 (TLR2) and FcεR1 agonists, in murine mast cells prestimulated with lipopolysaccharide (LPS). Additionally, we evaluated some stimulatory and inhibitory signaling molecules potentially involved in these phenomena.</p> <p>Methods</p> <p>MC/9 cells and primary bone marrow-derived mast cells obtained from C57BL/6 and TLR4^-/-knock-out mice were sensitized to DNP-HSA (antigen) by incubation with DNP-IgE and were prestimulated with LPS for 18 hr prior to stimulation. Cultures were stimulated with LPS or Pam3Cys-Ser-(Lys)4 3HCl (P3C), a TLR2 agonist, individually or in combination with antigen. The production of IL-6 and TNFα, the phosphorylation of NFκB and p38 MAPK, and the expression of TLR4 and SOCS-1 and -3 were analyzed.</p> <p>Results</p> <p>We found that production of TNFα and IL-6 in murine mast cells that have been pretreated with LPS and challenged with TLR4 (LPS) or -2 (P3C) agonists was reduced, phenomena described as endotoxin tolerance (LPS) and cross-tolerance (P3C), respectively. The expression of TLR4 was not affected by LPS pretreatment. Our results show that the FcεR1 agonist DNP-HSA (antigen) interacts synergistically with LPS or P3C to markedly enhance production of cytokines (TNFα and IL-6). This synergistic effect with LPS and P3C was also attenuated by LPS pretreatment and was mediated by TLR4. These results may be attributed to the reduction in phosphorylation of the mitogen-activated protein kinase (MAPK), p38, and the transcription factor NFκB, as well as to an increase in the expression of the suppressors of cytokine signaling (SOCS)-1 and -3 proteins in LPS-pretreated mast cells.</p> <p>Conclusions</p> <p>These findings can be explored with respect to the modulation of inflammatory responses associated with infectious and allergic processes in future studies.</p

Diverging Mechanisms of Activation of Chemokine Receptors Revealed by Novel Chemokine Agonists

CXCL8/interleukin-8 is a pro-inflammatory chemokine that triggers pleiotropic responses, including inflammation, angiogenesis, wound healing and tumorigenesis. We engineered the first selective CXCR1 agonists on the basis of residue substitutions in the conserved ELR triad and CXC motif of CXCL8. Our data reveal that the molecular mechanisms of activation of CXCR1 and CXCR2 are distinct: the N-loop of CXCL8 is the major determinant for CXCR1 activation, whereas the N-terminus of CXCL8 (ELR and CXC) is essential for CXCR2 activation. We also found that activation of CXCR1 cross-desensitized CXCR2 responses in human neutrophils co-expressing both receptors, indicating that these novel CXCR1 agonists represent a new class of anti-inflammatory agents. Further, these selective CXCR1 agonists will aid at elucidating the functional significance of CXCR1 in vivo under pathophysiological conditions