Care management of the agitation or aggressiveness crisis in patients with TBI. Systematic review of the literature and practice recommendations

AbstractThe agitation crisis in the awakening phase after traumatic brain injury (TBI) is one of the most difficult behavioral disorders to alleviate. Current treatment options are heterogeneous and may involve excessive sedation. Practice guidelines are required by professionals in charge of TBI patients. Few reviews were published but those are old and based on expert opinions. The purpose of this work is to propose evidence-based guidelines to treat the agitation crisis.MethodsThe elaboration of these guidelines followed the procedure validated by the French health authority for good practice recommendations, close to the Prisma statement. Guidelines were elaborated on the basis of a systematic and critical review of the literature.ResultsTwenty-eight articles concerning 376 patients were analyzed. Recommendations are: when faced with an agitation crisis, the management strategy implies to search for an underlying factor that should be treated such as pain, acute sepsis, and drug adverse effect (expert opinion). Physical restraints should be discarded when possible (expert opinion). Neuroleptic agent with a marketing authorization can be used in order to obtain a quick sedation so as to protect the patient from himself, closed ones or the healthcare team but the duration should be as short as possible (expert opinion). The efficacy of beta-blockers and antiepileptics with mood regulation effects like carbamazepine and valproate yield the most compelling evidence and should be preferably used when a background regimen is envisioned (grade B for beta-blocker and C for antiepileptics). Neuroleptics, antidepressants, benzodiazepines, buspirone may be prescribed but are considered second-line treatments (expert opinion).ConclusionThis study provides a strategy for treating the agitation crisis based on scientific data and expert opinion. The level of evidence remains low and published data are often old. New studies are essential to validate results from previous studies and test new drugs and non-pharmaceutical therapies

What are Hybrid Development Methods Made Of?

Regardless of company size or industry sector, a majority of project teams and companies use customized processes that combine different development methods-so-called hybrid development methods. Even though such hybrid development methods are highly individualized, a common understanding of how to systematically construct synergetic practices is missing. Based on 1,467 data points from a large-scale online survey among practitioners, we study the current state of practice in process use to answer the question: What are hybrid development methods made of? Our findings reveal that only eight methods and few practices build the core of modern software development. This small set allows for statistically constructing hybrid development methods

Hypothalamic Neuroendocrine Circuitry is Programmed by Maternal Obesity: Interaction with Postnatal Nutritional Environment

Objective: Early life nutrition is critical for the development of hypothalamic neurons involved in energy homeostasis. We previously showed that intrauterine and early postnatal overnutrition programmed hypothalamic neurons expressing the appetite stimulator neuropeptide Y (NPY) and suppressor proopiomelanocortin (POMC) in offspring at weaning. However, the long-term effects of such programming and its interactions with post-weaning high-fat-diet (HFD) consumption are unclear. Research Design and Methods: Female Sprague Dawley rats were exposed to chow or HFD for 5 weeks before mating, throughout gestation and lactation. On postnatal day 1, litters were adjusted to 3/litter to induce postnatal overnutrition (vs. 12 in control). At postnatal day 20, half of the rats from each maternal group were weaned onto chow or HFD for 15 weeks. Hypothalamic appetite regulators, and fuel (glucose and lipid) metabolic markers were measured. Results: Offspring from obese dams gained more weight than those from lean dams independent of post-weaning diet. Maternal obesity interacted with post-weaning HFD consumption to cause greater levels of hyperphagia, adiposity, hyperlipidemia, and glucose intolerance in offspring. This was linked to increased hypothalamic NPY signaling and leptin resistance in adult offspring. Litter size reduction had a detrimental impact on insulin and adiponectin, while hypothalamic NPY and POMC mRNA expression were suppressed in the face of normal energy intake and weight gain. Conclusions: Maternal obesity, postnatal litter size reduction and post-weaning HFD consumption caused obesity via different neuroendocrine mechanims. There were strong additive effects of maternal obesity and post-weaning HFD consumption to increase the metabolic disorders in offspring. © 2009 Chen et al

What are Hybrid Development Methods Made Of? An Evidence-Based Characterization

Among the multitude of software development processes available, hardly any is used by the book. Regardless of company size or industry sector, a majority of project teams and companies use customized processes that combine different development methods— so-called hybrid development methods. Even though such hybrid development methods are highly individualized, a common understanding of how to systematically construct synergetic practices is missing. In this paper, we make a first step towards devising such guidelines. Grounded in 1,467 data points from a large-scale online survey among practitioners, we study the current state of practice in process use to answer the question: What are hybrid development methods made of? Our findings reveal that only eight methods and few practices build the core of modern software development. This small set allows for statistically constructing hybrid development methods. Using an 85% agreement level in the participants’ selections, we provide two examples illustrating how hybrid development methods are characterized by the practices they are made of. Our evidence-based analysis approach lays the foundation for devising hybrid development methods

The Intracellular Localization of APE 1 /Ref-1: More than a Passive Phenomenon?

Human apurinic/apyrimidinic endonuclease 1/redox effector factor-1 (APE1/Ref-1) is a perfect paradigm of the functional complexity of a biological macromolecule. First, it plays a crucial role, by both redox-dependent and –independent mechanisms, as a transcriptional coactivator for different transcription factors, either ubiquitous (i.e., AP-1, Egr-1, NF-κB, p53, HIF) or tissue-specific (i.e., PEBP-2, Pax-5 and -8, TTF-1), in controlling different cellular processes such as apoptosis, proliferation, and differentiation. Second, it acts, as an apurinic/apyrimidinic endonuclease, during the second step of the DNA base excision repair pathway, which is responsible for the repair of cellular alkylation and oxidative DNA damages. Third, it controls the intracellular reactive oxygen species production by negatively regulating the activity of the Ras-related GTPase Rac1. Despite these known functions of APE1/Ref-1, information is still scanty about the molecular mechanisms responsible for the coordinated control of its several activities. Some evidence suggests that the expression and subcellular localization of APE1/Ref-1 are finely tuned. APE1/Ref-1 is a ubiquitous protein, but its expression pattern differs according to the different cell types. APE1/Ref-1 subcellular localization is mainly nuclear, but cytoplasmic staining has also been reported, the latter being associated with mitochondria and/or presence within the endoplasmic reticulum. It is not by chance that both expression and subcellular localization are altered in several metabolic and proliferative disorders, such as in tumors and aging. Moreover, a fundamental role played by different posttranslational modifications in modulating APE1/Ref-1 functional activity is becoming evident. In the present review, we tried to put together a growing body of information concerning APE1/Ref-1's different functions, shedding new light on present and future directions to understand fully this unique molecule

Iridium-catalysed ortho-directed deuterium labelling of aromatic esters – an experimental and theoretical study on directing group chemoselectivity

Herein we report a combined experimental and theoretical study on the deuterium labelling of benzoate ester derivatives, utilizing our developed iridium N-heterocyclic carbene/phosphine catalysts. A range of benzoate esters were screened, including derivatives with electron-donating and -withdrawing groups in the para- position. The substrate scope, in terms of the alkoxy group, was studied and the nature of the catalyst counter-ion was shown to have a profound effect on the efficiency of isotope exchange. Finally, the observed chemoselectivity was rationalized by rate studies and theoretical calculations, and this insight was applied to the selective labelling of benzoate esters bearing a second directing group

The Natural Product Lepidiline A as an N-Heterocyclic Carbene Ligand Precursor in Complexes of the Type [Ir(cod)(NHC)PPh3)]X: Synthesis, Characterisation, and Application in Hydrogen Isotope Exchange Catalysis

A range of iridium(I) complexes of the type [Ir(cod)(NHC)PPh3)]X are reported, where the N-heterocyclic carbene (NHC) is derived from the naturally-occurring imidaozlium salt, Lepidiline A (1,3-dibenzyl-4,5-dimethylimidazolium chloride). A range of complexes were prepared, with a number of NHC ligands and counter-ions, and various steric and electronic parameters of these complexes were evaluated. The activity of the [Ir(cod)(NHC)PPh3)]X complexes in hydrogen isotope exchange reactions was then studied, and compared to established iridium(I) complexes

Mitigating Carlini & Wagner attacks with EGAN

Deep Learning models are experiencing a significant surge in popularity, expanding into various domains, including critical applications like object recognition in autonomous vehicles, where any failure could have fatal consequences. Given the importance of these models, it is crucial to address potential attacks that could impact their performance and jeopardize user safety. The specialized branch of Machine Learning dedicated to this study is known as Adversarial Machine Learning. In this study, we will assess the effectiveness of Carlini & Wagner attacks. Additionally, we emphasize the importance of implementing proactive security measures to defend Deep Learning models. To enhance the model's resilience against potential threats, we employ a defense network called Encoding Generative Adversarial Networks. This comprehensive analysis will not only provide valuable insights into the vulnerability of models to different attacks but also contribute to the development of more robust and advanced strategies to protect Deep Learning models in critical applications. These findings are essential for increasing the security and reliability of artificial intelligence in environments that demand exceptional accuracy and dependability.Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tech

Aspergillosis, avian species and the one health perspective : the possible importance of birds in azole resistance

© 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).The One Health context considers health based on three pillars: humans, animals, and environment. This approach is a strong ally in the surveillance of infectious diseases and in the development of prevention strategies. Aspergillus spp. are fungi that fit substantially in this context, in view of their ubiquity, as well as their importance as plant pathogens, and potentially fatal pathogens for, particularly, humans and avian species. In addition, the emergence of azole resistance, mainly in Aspergillus fumigatus sensu stricto, and the proven role of fungicides widely used on crops, reinforces the need for a multidisciplinary approach to this problem. Avian species are involved in short and long distance travel between different types of landscapes, such as agricultural fields, natural environments and urban environments. Thus, birds can play an important role in the dispersion of Aspergillus, and of special concern, azole-resistant strains. In addition, some bird species are particularly susceptible to aspergillosis. Therefore, avian aspergillosis could be considered as an environmental health indicator. In this review, aspergillosis in humans and birds will be discussed, with focus on the presence of Aspergillus in the environment. We will relate these issues with the emergence of azole resistance on Aspergillus. These topics will be therefore considered and reviewed from the “One Health” perspective.This study was supported by the International Cooperation Program financed by Brazilian Federal Agency for Support and Evaluation of Graduate Education within the Ministry of Education of Brazil (CAPES), under the Capes-Print Program and PDSE Program—Finance Code 001info:eu-repo/semantics/publishedVersio