Oxidative stress (OS) refers to the imbalance between the generation of reactive oxygen species (ROS) and the ability to scavenge these ROS by endogenous antioxidant systems, where ROS overwhelms the ...antioxidant capacity. Excessive presence of ROS results in irreversible damage to cell membranes, DNA, and other cellular structures by oxidizing lipids, proteins, and nucleic acids. Oxidative stress plays a crucial role in the pathogenesis of cardiovascular diseases related to hypoxia, cardiotoxicity and ischemia-reperfusion. Here, we describe the participation of OS in the pathophysiology of cardiovascular conditions such as myocardial infarction, anthracycline cardiotoxicity and congenital heart disease. This review focuses on the different clinical events where redox factors and OS are related to cardiovascular pathophysiology, giving to support for novel pharmacological therapies such as omega 3 fatty acids, non-selective betablockers and microRNAs.
•A general model for decision support for the operating room scheduling problem, using integer optimization.•A novel approach to introduce case length uncertainty into the problem formulation.•Use of ...chance constraints to control uncertainty, showing how these can be implemented in the integer optimization model.•Experimental results, using historical instances, show that this approach improves schedule performance significantly.•The analysis shows the improvement gained if it is possible to add flexibility to physicians' assignment to surgeries.
The operating theater is one of the most expensive units in the hospital, representing up to 40% of the total expenses. Because of its importance, the operating room scheduling problem has been addressed from many different perspectives since the early 1960s. One of the main difficulties that has reduced the applicability of the current results is the high variability in surgery duration, making schedule recommendations hard to implement.
In this work, we propose a time-indexed scheduling formulation to solve the operational problem. Our main contribution is that we propose the use of chance constraints related to the surgery duration’s probability distribution for each surgeon to improve the scheduling performance. We show how to implement these chance constraints as linear ones in our time-indexed formulation, enhancing the performance of the resulting schedules significantly.
Through data analysis of real historical instances, we develop specific constraints that improve the schedule, reducing the need for overtime without affecting the utilization significantly. Furthermore, these constraints give the operating room manager the possibility of balancing overtime and utilization through a tuning parameter in our formulation. Finally, through simulations and the use of real instances, we report the performance for four different metrics, showing the importance of using historical data to get the right balance between the utilization and overtime.
Abstract
Allostasis provides a supporting role to the homeostatic control of biological variables in mammalian species. While the concept of homeostasis is related to the control of variables within ...a set point or range that are essential to life, allostasis refers to systems that facilitate adaptation to challenges that the organism faces and the new requirements for survival. Essential for such adaptation is the role played by the brain in eliciting neural and neuroendocrine responses. Reproductive function is fundamental for the survival of species but is costly in energetic terms and requires a synchrony with an ever-changing environment. Thus, in many species reproductive function is blocked or delayed over immediate challenges. This review will cover the physiological systems and neuroendocrine pathways that supply allostatic control over reproductive neuroendocrine systems. Light, hypoxia, temperature, nutrition, psychosocial, and immune mediators influence the neuroendocrine control of reproductive functions through pathways that are confluent at the paraventricular nucleus; however, understanding of the integrative responses to these stimuli has not been clarified. Likely, the ultimate consequence of these allostatic mechanisms is the modification of kisspeptin and gonadotropin-releasing hormone neuronal activity, thus compromising reproduction function in the short term, while preserving species survivability.
Dexmedetomidine (DEX) is a highly selective α2-adrenergic agonist with sedative and analgesic properties, with minimal respiratory effects. It is used as a sedative in the intensive care unit and the ...operating room. The opioid-sparing effect and the absence of respiratory effects make dexmedetomidine an attractive adjuvant drug for anesthesia in obese patients who are at an increased risk for postoperative respiratory complications. The pharmacodynamic effects on the cardiovascular system are known; however the mechanisms that induce cardioprotection are still under study. Regarding the pharmacokinetics properties, this drug is extensively metabolized in the liver by the uridine diphosphate glucuronosyltransferases. It has a relatively high hepatic extraction ratio, and therefore, its metabolism is dependent on liver blood flow. This review shows, from a basic clinical approach, the evidence supporting the use of dexmedetomidine in different settings, from its use in animal models of ischemia-reperfusion, and cardioprotective signaling pathways. In addition, pharmacokinetics and pharmacodynamics studies in obese subjects and the management of patients subjected to mechanical ventilation are described. Moreover, the clinical efficacy of delirium incidence in patients with indication of non-invasive ventilation is shown. Finally, the available evidence from DEX is described by a group of Chilean pharmacologists and clinicians who have worked for more than 10 years on DEX.
Comprehending ecological dynamics requires not only knowledge of modern communities but also detailed reconstructions of ecosystem history. Ancient DNA (aDNA) metabarcoding allows biodiversity ...responses to major climatic change to be explored at different spatial and temporal scales. We extracted aDNA preserved in fossil rodent middens to reconstruct late Quaternary vegetation dynamics in the hyperarid Atacama Desert. By comparing our paleo‐informed millennial record with contemporary observations of interannual variations in diversity, we show local plant communities behave differentially at different timescales. In the interannual (years to decades) time frame, only annual herbaceous expand and contract their distributional ranges (emerging from persistent seed banks) in response to precipitation, whereas perennials distribution appears to be extraordinarily resilient. In contrast, at longer timescales (thousands of years) many perennial species were displaced up to 1,000 m downslope during pluvial events. Given ongoing and future natural and anthropogenically induced climate change, our results not only provide baselines for vegetation in the Atacama Desert, but also help to inform how these and other high mountain plant communities may respond to fluctuations of climate in the future.
Comprehending ecological dynamics requires not only knowledge of modern communities but also detailed reconstructions of ecosystem history. In this study, we compared long‐term records of Atacama Desert plant biodiversity preserved in fossils to interannual variations in diversity. In the interannual (years to decades) time frame, only annual herbaceous expand and contract their distributional ranges in response to precipitation. In contrast, at longer timescales (thousands of years) many perennial and annual species were displaced up to 1,000 m downslope during pluvial events. Our results show how plant communities have responded to past climate change and could help predict how they may respond in the future.
•A constant approximation algorithm for the resource cost aware scheduling problem.•The algorithm handles general job-dependent resource cost functions.•Considers arbitrary precedence constraints and ...release dates.•The concept of α-speeds is introduced, which extend α-point techniques.•Experimental results on benchmark instances show small approximation ratios.
We are interested in the scheduling problem where there are several different resources that determine the speed at which a job runs and we pay depending on the amount of each resource that we use. This work is an extension of the resource dependent job processing time problem and the energy aware scheduling problems. We develop a new constant factor approximation algorithm for resource cost aware scheduling problems: the objective is to minimize the sum of the total cost of resources and the total weighted completion time in the one machine non-preemptive setting, allowing for arbitrary precedence constraints and release dates. Our algorithm handles general job-dependent resource cost functions. We also analyze the practical performance of our algorithms, showing that it is significantly superior to the theoretical bounds and in fact it is very close to optimal. The analysis is done using simulations and real instances, which are left publicly available for future benchmarks. We also present additional heuristic improvements and we study their performance in other settings.
The prognostics and health management disciplines provide an efficient solution to improve a system’s durability, taking advantage of its lifespan in functionality before a failure appears. ...Prognostics are performed to estimate the system or subsystem’s remaining useful life (RUL). This estimation can be used as a supply in decision-making within maintenance plans and procedures. This work focuses on prognostics by developing a recurrent neural network and a forecasting method called Prophet to measure the performance quality in RUL estimation. We apply this approach to degradation signals, which do not need to be monotonical. Finally, we test our system using data from new generation telescopes in real-world applications.
Kisspeptin modulates GnRH secretion in mammals and peripheral administration of 10-amino acid fragment of kisspeptin (Kp10) induces LH release and ovulation in cattle. Experiments were done to ...determine if iv administration of kisspeptin will activate GnRH neurons (i.e., after crossing the blood-brain barrier) and if pre-treatment with a GnRH receptor blocker will alter kisspeptin-induced LH release (from gonadotrophs) and ovulation. In Experiment 1, cows (n = 3 per group) were given human-Kisspeptin10 (hKp10; 3 x 15 mg iv at 60-min intervals) or normal saline and euthanized 150 min after treatment was initiated. Every 20th free-floating section (50 μm thickness) from the preoptic area to hypothalamus was double immunostained to colocalize GnRH- (DAB) and activated neurons (cFOS; Nickel-DAB). Kisspeptin induced plasma LH release from 15 to 150 min (P = 0.01) but the proportion of activated GnRH neurons did not differ between groups (5.8% and 3.5%, respectively; P = 0.11). Immunogold electron microscopy detected close contacts between kisspeptin fibers and GnRH terminals in the median eminence. In Experiment 2, pubertal heifers (n = 5 per group) were treated with 1) hKp10 iv, 2) Cetrorelix (GnRH antagonist; im) + hKp10 iv or 3) saline on Day 6 of the follicular wave under low-progesterone condition. A rise in plasma LH concentration was detected from 15 to 240 min in the hKp10 group but not in cetrorelix or control group (P<0.001). Ovulations were detected only in the hKp10 group (4/5; P = 0.02). Cetrorelix treatment was associated with regression of the preovulatory dominant follicle and emergence of a new follicular wave 3.4±0.75 days after the treatment in all five heifers. Results support the hypothesis that the effect of peripheral kisspeptin is mediated downstream of GnRH synthesis and does not involve GnRH-independent LH release from gonadotrophs. Peripheral kisspeptin may release pre-synthesized GnRH from the nerve terminals in areas outside the blood-brain barrier.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Summary
Plant–plant positive interactions are key drivers of community structure. Yet, the underlying molecular mechanisms of facilitation processes remain unexplored. We investigated the ‘nursing’ ...effect of Maihueniopsis camachoi, a cactus that thrives in the Atacama Desert between c. 2800 and 3800 m above sea level. We hypothesised that an important protective factor is thermal amelioration of less cold‐tolerant species with a corresponding impact on molecular phenotypes.
To test this hypothesis, we compared plant cover and temperatures within the cactus foliage with open areas and modelled the effect of temperatures on plant distribution. We combined eco‐metabolomics and machine learning to test the molecular consequences of this association.
Multiple species benefited from the interaction with M. camachoi. A conspicuous example was the extended distribution of Atriplex imbricata to colder elevations in association with M. camachoi (400 m higher as compared to plants in open areas). Metabolomics identified 93 biochemical markers predicting the interaction status of A. imbricata with 79% accuracy, independently of year.
These findings place M. camachoi as a key species in Atacama plant communities, driving local biodiversity with an impact on molecular phenotypes of nursed species. Our results support the stress‐gradient hypothesis and provide pioneer insights into the metabolic consequences of facilitation.
In the female camelid, systemic administration of NGF induces a preovulatory LH surge that results in ovulation, but the effects of seminal NGF in the male are unknown. In the present study, we ...tested the hypothesis that the LH-releasing pathway of NGF is present in male camelids. In Experiment 1, male llamas and alpacas were treated with NGF or GnRH (n = 2 llamas and 3 alpacas) and blood samples were collected from 1 h before to 3 h after treatment. Plasma LH concentrations increased after treatment in a surge-like fashion in both GnRH- and NGF-treated groups, but concentrations reached a maximum 2.5 times higher and remained elevated for at least 2 h longer in the NGF-treated group (treatment-by-time interaction, P = 0.01). In Experiment 2, we evaluated the LH and testosterone response to NGF vs saline treatment (n = 3 llamas and 3 alpacas). The LH response to NGF was similar to that in Experiment 1, and plasma testosterone concentrations were higher in the NGF group than in the saline group at 2, 4 and 6 h after treatment (P < 0.05). Results support the hypothesis that the LH-releasing pathway for NGF exists in male South American camelids. The LH response to NGF sustained circulating testosterone concentrations in llamas, suggesting a moderate role of NGF in testosterone secretion.
•NGF induces LH release in male camelids.•NGF -induced LH secretion may be related to testosterone secretion in male llamas and alpacas.
PDF
