Compliance with antibiotic therapy guidelines in french paediatric intensive care units: a multicentre observational study.

BACKGROUND: Bacterial infections (BIs) are widespread in ICUs. The aims of this study were to assess compliance with antibiotic recommendations and factors associated with non-compliance. METHODS: We conducted an observational study in eight French Paediatric and Neonatal ICUs with an antimicrobial stewardship programme (ASP) organised once a week for the most part. All children receiving antibiotics for a suspected or proven BI were evaluated. Newborns < 72 h old, neonates < 37 weeks, age ≥ 18 years and children under surgical antimicrobial prophylaxis were excluded. RESULTS: 139 suspected (or proven) BI episodes in 134 children were prospectively included during six separate time-periods over one year. The final diagnosis was 26.6% with no BI, 40.3% presumed (i.e., not documented) BI and 35.3% documented BI. Non-compliance with antibiotic recommendations occurred in 51.1%. The main reasons for non-compliance were inappropriate choice of antimicrobials (27.3%), duration of one or more antimicrobials (26.3%) and length of antibiotic therapy (18.0%). In multivariate analyses, the main independent risk factors for non-compliance were prescribing ≥ 2 antibiotics (OR 4.06, 95%CI 1.69-9.74, p = 0.0017), duration of broad-spectrum antibiotic therapy ≥ 4 days (OR 2.59, 95%CI 1.16-5.78, p = 0.0199), neurologic compromise at ICU admission (OR 3.41, 95%CI 1.04-11.20, p = 0.0431), suspected catheter-related bacteraemia (ORs 3.70 and 5.42, 95%CIs 1.32 to 15.07, p < 0.02), a BI site classified as "other" (ORs 3.29 and 15.88, 95%CIs 1.16 to 104.76, p < 0.03), sepsis with ≥ 2 organ dysfunctions (OR 4.21, 95%CI 1.42-12.55, p = 0.0098), late-onset ventilator-associated pneumonia (OR 6.30, 95%CI 1.15-34.44, p = 0.0338) and ≥ 1 risk factor for extended-spectrum ß-lactamase-producing Enterobacteriaceae (OR 2.56, 95%CI 1.07-6.14, p = 0.0353). Main independent factors for compliance were using antibiotic therapy protocols (OR 0.42, 95%CI 0.19-0.92, p = 0.0313), respiratory failure at ICU admission (OR 0.36, 95%CI 0.14-0.90, p = 0.0281) and aspiration pneumonia (OR 0.37, 95%CI 0.14-0.99, p = 0.0486). CONCLUSIONS: Half of antibiotic prescriptions remain non-compliant with guidelines. Intensivists should reassess on a day-to-day basis the benefit of using several antimicrobials or any broad-spectrum antibiotics and stop antibiotics that are no longer indicated. Developing consensus about treating specific illnesses and using department protocols seem necessary to reduce non-compliance. A daily ASP could also improve compliance in these situations. TRIAL REGISTRATION: ClinicalTrials.gov: number NCT04642560. The date of first trial registration was 24/11/2020.

The concept of tissue regeneration: Epistemological and historical enquiry from early ideas on the regeneration of bone to the microscopic observations of the regeneration of peripheral nerves.

This paper examines the epistemological history of physiological tissue regeneration theories from Antiquity to the present time focusing on early clinical observations, microscopic investigations of the 19th C. and molecular aspects of the regeneration of peripheral nerves. We aim to show underlying theoretical implications at stake over centuries, with an extreme diversity of local contexts, while slowly emerging ideas were progressively built in the framework of cell theory and that of molecular biology. The overall epistemological lesson is that this long history is far from finished and requires novel experiments and perspectives, as well as the careful inspection of its rich past, as a true scientific tradition, in order to better understand what is nervous regeneration and how we can use it in medicine.

Trace metal concentrations, fluxes, and potential human health risks in West Africa rivers: a case study on the Bia, Tanoé, and Comoé rivers (Cote d'Ivoire).

Downstream water pollution resulting from anthropogenic pressures on upstream water can cause conflicts, especially in transboundary rivers basins. This study assessed trace metals cadmium, lead, copper, and iron total concentrations, fluxes, and the potential human health risks through ingestion or dermal contact of waters at the mouth of three West African transboundary rivers: the Comoé, Bia, and Tanoé rivers. The results showed highest total concentrations during the months of May and October and statistically comparable concentrations in the rivers. The fluxes discharged to the Atlantic Ocean through the Aby and Ebrie Lagoons are as high as average values found elsewhere in the World. Trace metals lead, copper, and iron fluxes were highest during the month of October in the Bia, Tanoé, and Comoé rivers. The cadmium flux was highest during the month of October in the Bia and Comoé rivers, and during the months of February and December in the Tanoé River, indicating that contamination came mainly from upstream waters and the draining of the river basins. The Pearson correlation analysis showed that the trace metals were mainly from anthropogenic sources including gold mining and agriculture. The total concentrations were lower than international guidelines set by the World Health Organization (WHO). However, the potential human health risk assessment results suggest a significant likelihood of community exposure to harmful effects but not to cancers through water ingestion. This work recommends including small rivers when assessing global river metal fluxes to the ocean and also reducing upstream inputs from human activities to mitigate downstream river water pollution.

140 Years of the Leçons sur l'histologie du système nerveux: the pioneering description of the nodes of Ranvier.

This paper reviews aspects of the life and work of Professor Louis Ranvier 140 years after the publication of Leçons sur l'histologie du système nerveux, published in 1878, and shows the importance of the histological description of myelinated fibers of the nodes of Ranvier.

140 Years of the Leçons sur l'histologie du système nerveux: the pioneering description of the nodes of Ranvier / 140 Anos da Leçons sur l'histologie du système nerveux: a descrição pioneira dos nodos de Ranvier

ABSTRACT This paper reviews aspects of the life and work of Professor Louis Ranvier 140 years after the publication of Leçons sur l'histologie du système nerveux, published in 1878, and shows the importance of the histological description of myelinated fibers of the nodes of Ranvier.

RESUMO Os autores apresentam uma revisão sobre aspectos da vida e obra do Professor Louis Ranvier 140 anos após a publicação de seu livro Leçons sur l'histologie du système nerveux publicado em 1878 e mostra a importância da descrição histológica nas fibras mielínicas dos nodos de Ranvier.

Systemic PPARγ deletion in mice provokes lipoatrophy, organomegaly, severe type 2 diabetes and metabolic inflexibility.

BACKGROUND: The peroxisome proliferator-activated receptor γ (PPARγ) is a ligand-dependent transcription factor involved in many aspects of metabolism, immune response and development. Numerous studies relying on tissue-specific invalidation of the Pparg gene have shown distinct facets of its activity, whereas the effects of its systemic inactivation remain unexplored due to embryonic lethality. By maintaining PPARγ expression in the placenta, we recently generated a mouse model carrying Pparg full body deletion (PpargΔ/Δ), which in contrast to a previously published model is totally deprived of any form of adipose tissue. Herein, we propose an in-depth study of the metabolic alterations observed in this new model. METHODS: Young adult mice, both males and females analyzed separately, were first phenotyped for their gross anatomical alterations. Systemic metabolic parameters were analyzed in the blood, in static and in dynamic conditions. A full exploration of energy metabolism was performed in calorimetric cages as well as in metabolic cages. Our study was completed by expression analyses of a set of specific genes. MAIN FINDINGS: PpargΔ/Δ mice show a striking complete absence of any form of adipose tissue, which triggers a complex metabolic phenotype including increased lean mass with organomegaly, hypermetabolism, urinary energy loss, hyperphagia, and increased amino acid metabolism. PpargΔ/Δ mice develop severe type 2 diabetes, characterized by hyperglycemia, hyperinsulinemia, polyuria and polydispsia. They show a remarkable metabolic inflexibility, as indicated by the inability to shift substrate oxidation between glucose and lipids, in both ad libitum fed state and fed/fasted/refed transitions. Moreover, upon fasting PpargΔ/Δ mice enter a severe hypometabolic state. CONCLUSIONS: Our data comprehensively describe the impact of lipoatrophy on metabolic homeostasis. As such, the presented data on PpargΔ/Δ mice gives new clues on what and how to explore severe lipodystrophy and its subsequent metabolic complications in human.

On-Site Validation of a Microwave Breast Imaging System, before First Patient Study.

This paper presents the Wavelia microwave breast imaging system that has been recently installed at the Galway University Hospital, Ireland, for a first-in-human pilot clinical test. Microwave breast imaging has been extensively investigated over the last two decades as an alternative imaging modality that could potentially bring complementary information to state-of-the-art modalities such as X-ray mammography. Following an overview of the main working principles of this technology, the Wavelia imaging system architecture is presented, as are the radar signal processing algorithms that are used in forming the microwave images in which small tumors could be detectable for disease diagnosis. The methodology and specific quality metrics that have been developed to properly evaluate and validate the performance of the imaging system using complex breast phantoms that are scanned at controlled measurement conditions are also presented in the paper. Indicative results from the application of this methodology to the on-site validation of the imaging system after its installation at the hospital for pilot clinical testing are thoroughly presented and discussed. Given that the imaging system is still at the prototype level of development, a rigorous quality assessment and system validation at nominal operating conditions is very important in order to ensure high-quality clinical data collection.

Neuroscience without borders: Preserving the history of neuroscience.

Over the last 50 years, neuroscience has enjoyed a spectacular development, with many discoveries greatly expanding our knowledge of brain function. Despite this progress, there has been a disregard for preserving the history of these discoveries. In many European countries, historic objects, instruments, and archives are neglected, while libraries and museums specifically focusing on neuroscience have been closed or drastically cut back. To reverse this trend, the Federation of European Neuroscience Societies (FENS) has organized a number of projects, including (a) the History of Neuroscience online projects, (b) the European Brain Museum Project (EBM), (c) the History online library, (d) the FENS meeting History Corner, (e) history lectures in historic venues, and (f) a series of history seminars in various European venues. These projects aim to stimulate research in, and increase awareness of, the history of European neuroscience. Our seminars have attracted large audiences of students, researchers, and the general public, who have supported our initiatives for the preservation of the history of neuroscience for future generations and for the promotion of interest in the history of neuroscience. It is therefore urgent to develop new methods for preserving our history, not only in Europe but also in the rest of the world, and to increase greatly teaching and research in this important aspect of our scientific and cultural legacy.

Historical concepts on the relations between nerves and muscles.

This review addresses the history since antiquity of studies on the anatomical and functional relations between nerves and muscles, and the progressive use of newer approaches to this topic. By the Hippocratic era (almost 2500 years ago) the digestive, circulatory and nervous systems were thought to participate in the production of animal spirits. This concept had strong support for nervous conduction, even after the dawn of electrophysiology in the late 18th C. The idea that these spirits explained the nature of the motor command to muscles continued to prevail until work in the mid-to-late 19th C dispelled the concept of "fluid/spirit" transmission by measurements of nerve "action currents" and conduction velocity. In parallel with this work, the functional relations between nerves and muscles were studied with the use of curare, which continued well into the 20th C. In the late 19th C the debate was formalized about whether transmission at the motor endplate was electrical or chemical, which continued as the "soup" vs. "sparks" battle until, surprisingly, the late 1960s. The concept of the motor unit was introduced in the 1920s, this being defined as a motor neuron in the spinal cord connecting to a specific set of muscle fibers. This development accelerated work on two-way trophic relations between nerve and muscles and their essential plasticity in response to the demands of usage and disease. Thus, the relation between nerves and muscles has been on the forefront of neuroscience since antiquity.

Discovering the African freshwater "torpedo": legendary Ethiopia, religious controversies, and a catfish capable of reanimating dead fish.

The electric catfishes of African rivers and lakes, once depicted on Egyptian tomb art, have been largely overlooked in histories and reviews of electric fish biology and animal electricity. This article examines how Westerners, especially Dominican and Jesuit missionaries, discovered them in Ethiopia and other parts of Africa at the beginning of the seventeenth century. What transpired took place against the backdrop of tales involving the Bible, Prester John's mythical empire, and imaginary animals with fabulous powers. In effect, how they were found is related to attempts to convert Ethiopian Christians to true Catholicism, hopes of discovering great riches, and opportunities to trade, and not with the efforts of skilled natural philosophers to document and conduct experiments on the wildlife of this continent. Nevertheless, the early descriptions by Europeans circulated, and during the next century these catfishes began to be used in experiments that helped to make animal electricity a reality.

The emergence of the "motoneuron concept": from the early 19th C to the beginning of the 20th C.

This article addresses the emergence of the "motoneuron concept," i.e., the idea that this cell had properties of particular advantage for its control of muscle activation. The motor function of the ventral roots was established early in the 19th C and the term "motor cell," (or "motor nerve cell") was introduced shortly thereafter by Albrecht von Kölliker and some other histologists. They knew that motor cells were among the neurons with the largest soma in vertebrates and for this reason they were, and remained for many decades, the best and most studied neuronal model. The work of clinicians like Guillaume Duchenne de Boulogne and Jean-Martin Charcot on motor degenerative syndromes began before a clear description of motor cells was available, because it was initially more difficult to establish whether the deficits of paralysis and muscle weakness were due to neuronal or muscular lesions. Next, the pioneering physiologist, Charles Sherrington, who was influenced greatly by the anatomical contributions and speculations of Santiago Ramón y Cajal, used the term, "motor neuron," rather than motor cell for the neuron that he considered was functionally "the final common path" for providing command signals to the musculature. In the early 20th C he proposed that activation of a motor neuron resulted from the sum of its various excitatory and inhibitory CNS inputs. The contraction of motor neuron to "motoneuron(e)" was put into common usage by John Fulton (among possibly others) in 1926. The motoneuron concept is still evolving with new discoveries on the horizon.

[Claude Bernard and his successors on curare: epistemological questions at stake]. / Claude Bernard et ses suiveurs sur la question du curare : enjeux épistémologiques.

Long lasting polemics about the mechanisms of the action of curare took place at the Société de Biologie over thirty years. After a period during which poisoning protocols were developed on various animal species, where Claude Bernard, Vulpian and their colleagues were involved, German electrophysiology combined its results with new histological data about motor end-plates, elaborating a theory in which young physiologists fought against Claude Bernard's views and finally managed to convince him. According to the new theory proposed by Vulpian, curare blocked transmission between end-plate and muscle. This first draft of the neurotransmission theory helps us to understand the rise of a novel physiology in the context of the school of Claude Bernard with a better integration of disciplines and a more prominent faith in reductionism and materialism.

Louis Ranvier (1835-1922): the contribution of microscopy to physiology and the renewal of French general anatomy.

The French neurohistologist Louis-Antoine Ranvier (1835-1922), somewhat neglected in classical histories of nineteenth-century studies on the nervous system, developed a personal style, traditionally referred to as a synthesis between histology and physiology. Ranvier's research was not centered on the brain. Rather, he remained attached to the intimate nature of minute structures, with a style marked by the concept of generality. Ranvier's original style and role in the development of French histology and anatomie générale are analyzed, and their significance evaluated. Ranvier is reassessed as a prominent figure and as the leader in the renewal of the French anatomy.

The physiological construction of the neurone concept (1891-1952).

Steps in the physiological construction of the neurone concept are described. Early ideas on the function of the nerve cell led to later polemics on the neurone doctrine and the speculative attitude of histophysiology. Researches of Sherrington and Adrian emerged from a specific British context, and confronted American oscillography and Berger rhythm. At the end of various polemics, the neurone was constructed by the intracellular technique and the use of concepts borrowed from other sub-disciplines. Analysis of these paths demonstrates underlying disciplinary interactions as essential factors.

Direct and indirect interactions between cannabinoid CB1 receptor and group II metabotropic glutamate receptor signalling in layer V pyramidal neurons from the rat prefrontal cortex.

At proximal synapses from layer V pyramidal neurons from the rat prefrontal cortex, activation of group II metabotropic glutamate receptors (group II mGlu) by (2S,2'R,3'R)-2-(2',3'-dicarboxycyclopropyl) glycine (DCG IV) induced a long-lasting depression of excitatory postsynaptic currents. Paired-pulse experiments suggested that the depression was expressed presynaptically. Activation of type 1 cannabinoid receptors (CB1) by WIN 55,212-2 occluded the DCG IV-induced depression in a mutually occlusive manner. At the postsynaptic level, WIN 55,212-2 and DCG IV were also occlusive for the activation of extracellular signal-regulated kinase. The postsynaptic localization of active extracellular signal-regulated kinase was confirmed by immunocytochemistry after activation of CB1 receptors. However, phosphorylation of extracellular signal-regulated kinase in layer V pyramidal neurons was dependent on the activation of N-methyl-d-aspartate receptors, consequently to a release of glutamate in the local network. Group II mGlu were also shown to be involved in long-term changes in synaptic plasticity induced by high frequency stimulations. The group II mGlu antagonist (RS)-alpha-methylserine-O-phosphate monophenyl ester (MSOPPE) favoured long-term depression. However, no interaction was found between MSOPPE, WIN 55,212-2 and the CB1 receptor antagonist SR 141716A on the modulation of long-term depression or long-term potentiation and the effects of these drugs were rather additive. We suggest that CB1 receptor and group II mGlu signalling may interact through a presynaptic mechanism in the induction of a DCG IV-induced depression. Postsynaptically, an indirect interaction occurs for activation of extracellular signal-regulated kinase. However, none of these interactions seem to play a role in synaptic plasticities induced with high frequency stimulations.