Resuscitation Endpoints in Trauma

Fluid and blood resuscitation is the mainstay of therapy for the treatment of hemorrhagic shock, whether due to trauma or other etiology. Cessation of hemorrhage with rapid hemostatic techniques is the first priority in the treatment of traumatic hemorrhagic shock, with concomitant fluid resuscitation with blood and crystalloids to maintain perfusion and organ function. “Hypotensive” or “low-volume” resuscitation has become increasingly accepted in the prehospital resuscitation phase of trauma, prior to definitive hemorrhage control, since aggressive fluid resuscitation may increase bleeding. Resuscitation after hemorrhage control is focused on restoration of tissue oxygenation. Efforts to optimize resuscitation have used “resuscitation endpoints” as markers of adequacy of resuscitation. The resuscitation endpoints that have been evaluated include both global (restoration of blood pressure, heart rate and urine output, lactate, base deficit, mixed venous oxygen saturation, ventricular end-diastolic volume) and regional (gastric tonometry, near-infrared spectroscopy for measurement of muscle tissue oxygen saturation) measures. This review critically evaluates the evidence regarding the use of resuscitation endpoints in trauma.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/75386/1/j.1778-428X.2005.tb00127.x.pd

cGMP-Phosphodiesterase Inhibition Enhances Photic Responses and Synchronization of the Biological Circadian Clock in Rodents

The master circadian clock in mammals is located in the hypothalamic suprachiasmatic nuclei (SCN) and is synchronized by several environmental stimuli, mainly the light-dark (LD) cycle. Light pulses in the late subjective night induce phase advances in locomotor circadian rhythms and the expression of clock genes (such as Per1-2). The mechanism responsible for light-induced phase advances involves the activation of guanylyl cyclase (GC), cGMP and its related protein kinase (PKG). Pharmacological manipulation of cGMP by phosphodiesterase (PDE) inhibition (e.g., sildenafil) increases low-intensity light-induced circadian responses, which could reflect the ability of the cGMP-dependent pathway to directly affect the photic sensitivity of the master circadian clock within the SCN. Indeed, sildenafil is also able to increase the phase-shifting effect of saturating (1200 lux) light pulses leading to phase advances of about 9 hours, as well as in C57 a mouse strain that shows reduced phase advances. In addition, sildenafil was effective in both male and female hamsters, as well as after oral administration. Other PDE inhibitors (such as vardenafil and tadalafil) also increased light-induced phase advances of locomotor activity rhythms and accelerated reentrainment after a phase advance in the LD cycle. Pharmacological inhibition of the main downstream target of cGMP, PKG, blocked light-induced expression of Per1. Our results indicate that the cGMP-dependent pathway can directly modulate the light-induced expression of clock-genes within the SCN and the magnitude of light-induced phase advances of overt rhythms, and provide promising tools to design treatments for human circadian disruptions

Computational analysis of the evolutionarily conserved Missing In Metastasis/Metastasis Suppressor 1 gene predicts novel interactions, regulatory regions and transcriptional control

Missing in Metastasis (MIM), or Metastasis Suppressor 1 (MTSS1), is a highly conserved protein, which links the plasma membrane to the actin cytoskeleton. MIM has been implicated in various cancers, however, its modes of action remain largely enigmatic. Here, we performed an extensive in silico characterisation of MIM to gain better understanding of its function. We detected previously unappreciated functional motifs including adaptor protein (AP) complex interaction site and a C-helix, pointing to a role in endocytosis and regulation of actin dynamics, respectively. We also identified new functional regions, characterised with phosphorylation sites or distinct hydrophilic properties. Strong negative selection during evolution, yielding high conservation of MIM, has been combined with positive selection at key sites. Interestingly, our analysis of intra-molecular co-evolution revealed potential regulatory hotspots that coincided with reduced potentially\ua0pathogenic polymorphisms. We explored databases for the mutations and expression levels of MIM in cancer. Experimentally, we focused on chronic lymphocytic leukaemia (CLL), where MIM showed high overall expression, however, downregulation on poor prognosis samples. Finally, we propose strong conservation of MTSS1 also on the transcriptional level and predict novel transcriptional regulators. Our data highlight important targets for future studies on the role of MIM in different tissues and cancers

Tissue engineering of functional articular cartilage: the current status

Osteoarthritis is a degenerative joint disease characterized by pain and disability. It involves all ages and 70% of people aged >65 have some degree of osteoarthritis. Natural cartilage repair is limited because chondrocyte density and metabolism are low and cartilage has no blood supply. The results of joint-preserving treatment protocols such as debridement, mosaicplasty, perichondrium transplantation and autologous chondrocyte implantation vary largely and the average long-term result is unsatisfactory. One reason for limited clinical success is that most treatments require new cartilage to be formed at the site of a defect. However, the mechanical conditions at such sites are unfavorable for repair of the original damaged cartilage. Therefore, it is unlikely that healthy cartilage would form at these locations. The most promising method to circumvent this problem is to engineer mechanically stable cartilage ex vivo and to implant that into the damaged tissue area. This review outlines the issues related to the composition and functionality of tissue-engineered cartilage. In particular, the focus will be on the parameters cell source, signaling molecules, scaffolds and mechanical stimulation. In addition, the current status of tissue engineering of cartilage will be discussed, with the focus on extracellular matrix content, structure and its functionality

Effects of circadian disruption on physiology and pathology: from bench to clinic (and back)

Nested within the hypothalamus, the suprachiasmatic nuclei (SCN) represent a central biological clock that regulates daily and circadian (i.e., close to 24 h) rhythms in mammals. Besides the SCN, a number of peripheral oscillators throughout the body control local rhythms and are usually kept in pace by the central clock. In order to represent an adaptive value, circadian rhythms must be entrained by environmental signals or zeitgebers, the main one being the daily light?dark (LD) cycle. The SCN adopt a stable phase relationship with the LD cycle that, when challenged, results in abrupt or chronic changes in overt rhythms and, in turn, in physiological, behavioral, and metabolic variables. Changes in entrainment, both acute and chronic, may have severe consequences in human performance and pathological outcome. Indeed, animal models of desynchronization have become a useful tool to understand such changes and to evaluate potential treatments in human subjects. Here we review a number of alterations in circadian entrainment, including jet lag, social jet lag (i.e., desynchronization between body rhythms and normal time schedules), shift work, and exposure to nocturnal light, both in human subjects and in laboratory animals. Finally, we focus on the health consequences related to circadian/entrainment disorders and propose a number of approaches for the management of circadian desynchronization.Fil: Chiesa, Juan José. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Duhart, José Manuel. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Casiraghi, Leandro Pablo. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Paladino, Natalia. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Bussi, Ivana Leda. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Golombek, Diego Andrés. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentin

Far-from-equilibrium monopole dynamics in spin ice

Condensed matter in the low-temperature limit reveals exotic physics associated with unusual orders and excitations, with examples ranging from helium superfluidity1 to magnetic monopoles in spin ice2, 3. The far-from-equilibrium physics of such low-temperature states may be even more exotic, yet to access it in the laboratory remains a challenge. Here we demonstrate a simple and robust technique—the ‘magnetothermal avalanche quench’—and its use in the controlled creation of non-equilibrium populations of magnetic monopoles in spin ice at millikelvin temperatures. These populations are found to exhibit spontaneous dynamical effects that typify far-from-equilibrium systems and yet are captured by simple models. Our method thus opens new directions in the study of far-from-equilibrium states in spin ice and other exotic magnets

Natural interaction in video image investigation and its evaluation

Video image investigation has become an important way to protect the public security. Traditional paper-based investigation method lacks of natural interactive tools to organize case and clue information, leading to poor work efficiency and performance. By interviewing professional video analysts, the current study developed the mental model of the video image investigation and designed an interactive video image investigation system based on the mental model. To evaluate the naturalness and the efficiency of the newly designed system, a user study were conducted involving 28 volunteers. Half of them used the interactive video image investigation system, while the other half used traditional paper-based method to complete an investigation task with a set of real surveillance videos. Through the analysis of brain activity and behavioral indices, we found that the proposed interactive video image investigation system led to higher work efficiency, lower mental workload, and more positive emotional experience or approach motivational tendencies compared to traditional paper-based method. These results suggested the potential application of efficiency, mental workload, and emotional experience for the evaluation of the naturalness of an interactive system. © Springer International Publishing AG, part of Springer Nature 2018