Spatial MS multiomics on clinical prostate cancer tissues.

Mass spectrometry (MS) and MS imaging (MSI) are used extensively for both the spatial and bulk characterization of samples in lipidomics and proteomics workflows. These datasets are typically generated independently due to different requirements for sample preparation. However, modern omics technologies now provide higher sample throughput and deeper molecular coverage, which, in combination with more sophisticated bioinformatic and statistical pipelines, make generating multiomics data from a single sample a reality. In this workflow, we use spatial lipidomics data generated by matrix-assisted laser desorption/ionization MSI (MALDI-MSI) on prostate cancer (PCa) radical prostatectomy cores to guide the definition of tumor and benign tissue regions for laser capture microdissection (LCM) and bottom-up proteomics all on the same sample and using the same mass spectrometer. Accurate region of interest (ROI) mapping was facilitated by the SCiLS region mapper software and dissected regions were analyzed using a dia-PASEF workflow. A total of 5525 unique protein groups were identified from all dissected regions. Lysophosphatidylcholine acyltransferase 1 (LPCAT1), a lipid remodelling enzyme, was significantly enriched in the dissected regions of cancerous epithelium (CE) compared to benign epithelium (BE). The increased abundance of this protein was reflected in the lipidomics data with an increased ion intensity ratio for pairs of phosphatidylcholines (PC) and lysophosphatidylcholines (LPC) in CE compared to BE.

Infrared light elicits endothelium-dependent vasodilation in isolated occipital arteries of the rat via soluble guanylyl cyclase-dependent mechanisms.

The left and right occipital arteries provide blood supply to afferent cell bodies in the ipsilateral nodose and petrosal ganglia. This supply is free of an effective blood-ganglion barrier, so changes in occipital artery blood flow directly affect the access of circulating factors to the afferent cell bodies. The application of infrared (IR) light to modulate neural and other cell processes has yielded information about basic biological processes within tissues and is gaining traction as a potential therapy for a variety of disease processes. To address whether IR can directly modulate vascular function, we performed wire myography studies to determine the actions of IR on occipital arteries isolated from male Sprague-Dawley rats. Based on our previous research that functionally-important differences exist between occipital artery segments close to their origin at the external carotid artery (ECA) and those closer to the nodose ganglion, the occipital arteries were dissected into two segments, one closer to the ECA and the other closer to the nodose ganglion. Segments were constricted with 5-hydroxytryptamine to a level equal to 50% of the maximal response generated by the application of a high (80 mM) concentration of K+ ions. The direct application of pulsed IR (1,460 nm) for 5 s produced a rapid vasodilation in occipital arteries that was significantly more pronounced in segments closest to the ECA, although the ECA itself was minimally responsive. The vasodilation remained for a substantial time (at least 120 s) after cessation of IR application. The vasodilation during and following cessation of the IR application was markedly diminished in occipital arteries denuded of the endothelium. In addition, the vasodilation elicited by IR in endothelium-intact occipital arteries was substantially reduced in the presence of a selective inhibitor of the nitric oxide-sensitive guanylate cyclase, 1H-[1,2,4]oxadiazolo [4,3-a]quinoxalin-1-one (ODQ). It appears that IR causes endothelium-dependent, nitric-oxide-mediated vasodilation in the occipital arteries of the rat. The ability of IR to generate rapid and sustained vasodilation may provide new therapeutic approaches for restoring or improving blood flow to targeted tissues.

Examiners' perceptions of forensic mental health assessments conducted via videoconferencing.

The COVID-19 pandemic led to an acceleration in the adoption of videoconferencing (VC) for conducting forensic mental health evaluations (forensic mental health assessments [FMHA]). Two years into the COVID-19 pandemic, we administered a survey to 71 Minnesota-licensed forensic evaluators. Approximately two-thirds (65.7%) had started using VC for FMHA only after the pandemic, though a combined 84.5% reported performing FMHA via VC frequently at present. A striking 43.7% of respondents preferred VC for FMHA over in-person evaluation, and another 22.5% expressed no preference between modalities. Further, nearly 70% of respondents denied there were any populations for which they would never use VC to complete an FMHA. We conclude that the widespread adoption of VC for FMHA with the advent of the COVID-19 pandemic has induced a lasting change in the practice of FMHA. We postulate that with further advancements in technology and the development of testing instruments that can be administered online, the use of VC for FMHA will become standard practice.

The sound of a Martian dust devil.

Dust devils (convective vortices loaded with dust) are common at the surface of Mars, particularly at Jezero crater, the landing site of the Perseverance rover. They are indicators of atmospheric turbulence and are an important lifting mechanism for the Martian dust cycle. Improving our understanding of dust lifting and atmospheric transport is key for accurate simulation of the dust cycle and for the prediction of dust storms, in addition to being important for future space exploration as grain impacts are implicated in the degradation of hardware on the surface of Mars. Here we describe the sound of a Martian dust devil as recorded by the SuperCam instrument on the Perseverance rover. The dust devil encounter was also simultaneously imaged by the Perseverance rover's Navigation Camera and observed by several sensors in the Mars Environmental Dynamics Analyzer instrument. Combining these unique multi-sensorial data with modelling, we show that the dust devil was around 25 m large, at least 118 m tall, and passed directly over the rover travelling at approximately 5 m s-1. Acoustic signals of grain impacts recorded during the vortex encounter provide quantitative information about the number density of particles in the vortex. The sound of a Martian dust devil was inaccessible until SuperCam microphone recordings. This chance dust devil encounter demonstrates the potential of acoustic data for resolving the rapid wind structure of the Martian atmosphere and for directly quantifying wind-blown grain fluxes on Mars.

In situ recording of Mars soundscape.

Before the Perseverance rover landing, the acoustic environment of Mars was unknown. Models predicted that: (1) atmospheric turbulence changes at centimetre scales or smaller at the point where molecular viscosity converts kinetic energy into heat1, (2) the speed of sound varies at the surface with frequency2,3 and (3) high-frequency waves are strongly attenuated with distance in CO2 (refs. 2-4). However, theoretical models were uncertain because of a lack of experimental data at low pressure and the difficulty to characterize turbulence or attenuation in a closed environment. Here, using Perseverance microphone recordings, we present the first characterization of the acoustic environment on Mars and pressure fluctuations in the audible range and beyond, from 20 Hz to 50 kHz. We find that atmospheric sounds extend measurements of pressure variations down to 1,000 times smaller scales than ever observed before, showing a dissipative regime extending over five orders of magnitude in energy. Using point sources of sound (Ingenuity rotorcraft, laser-induced sparks), we highlight two distinct values for the speed of sound that are about 10 m s-1 apart below and above 240 Hz, a unique characteristic of low-pressure CO2-dominated atmosphere. We also provide the acoustic attenuation with distance above 2 kHz, allowing us to explain the large contribution of the CO2 vibrational relaxation in the audible range. These results establish a ground truth for the modelling of acoustic processes, which is critical for studies in atmospheres such as those of Mars and Venus.

Removal of optimal cutting temperature (O.C.T.) compound from embedded tissue for MALDI imaging of lipids.

Matrix-assisted laser desorption/ionisation mass spectrometry imaging (MALDI-MSI) is a common molecular imaging modality used to characterise the abundance and spatial distribution of lipids in situ. There are several technical challenges predominantly involving sample pre-treatment and preparation which have complicated the analysis of clinical tissues by MALDI-MSI. Firstly, the common embedding of samples in optimal cutting temperature (O.C.T.), which contains high concentrations of polyethylene glycol (PEG) polymers, causes analyte signal suppression during mass spectrometry (MS) by competing for available ions during ionisation. This suppressive effect has constrained the application of MALDI-MSI for the molecular mapping of clinical tissues. Secondly, the complexity of the mass spectra is obtained by the formation of multiple adduct ions. The process of analyte ion formation during MALDI can generate multiple m/z peaks from a single lipid species due to the presence of alkali salts in tissues, resulting in the suppression of protonated adduct formation and the generation of multiple near isobaric ions which produce overlapping spatial distributions. Presented is a method to simultaneously remove O.C.T. and endogenous salts. This approach was applied to lipid imaging in order to prevent analyte suppression, simplify data interpretation, and improve sensitivity by promoting lipid protonation and reducing the formation of alkali adducts.

The importance of aspirin, catheterization accuracy, and catheter design in external ventricular drainage-related hemorrhage: a multicenter study of 1002 procedures.

BACKGROUND: External ventricular drainage (EVD) is the commonest neurosurgical procedure performed in daily neurosurgical practice, but relatively few studies have investigated the incidence and risk factors of its related hemorrhagic complications. METHODS: This was a multicenter retrospective review of consecutive EVD procedures. Patients 18 years or older who underwent EVD and had a routine postoperative computed tomography (CT) scan performed within 24 hours were included. EVD-related hemorrhage was defined as new intracranial hemorrhage immediately adjacent or within the ventricular catheter trajectory. The volume of hemorrhage and the position of the catheter tip were assessed. A review of patient-, disease-, and surgery-related factors including the ventricular catheter design utilized was conducted. The Bonferroni correction was applied to the alpha level of significance (0.05) for multivariable analysis. RESULTS: Nine hundred sixty-two patients underwent 1002 EVD performed by neurosurgeons in the operating theater. Sixteen percent (154) of patients were on aspirin before the procedure. Thirty-four percent (333) of patients had intracerebral hemorrhage, 25% (251) had aneurysmal subarachnoid hemorrhage and 16% (158) had traumatic brain injury. The mean duration from EVD to the first postoperative CT scan was 20 ± 4 h. EVD-related hematomas were detected after 81 procedures with a per-catheter risk of 8.1%. Mean hematoma volume was 1.2 ± 3.3 ml. Most were less than 1 ml (grade I, 79%, 64), 1 to 15 ml (grade II) in 20% (16) and a single clot larger than 15 ml (grade III, 1%) were detected. Clinically significant hemorrhage that resulted in catheter occlusion occurred in 1.7% (17) of procedures. Most catheters (62%, 625) were optimally placed, i.e., its tip being within the ipsilateral frontal horn or third ventricle. Three non-antibiotic-impregnated ventricular catheter designs were used with 55% (550) being the 2.2-mm Integra™ catheter, 14% (137) being the 2.8-mm Medtronic™ catheter, and 31% (315) being the 3.1-mm Codman™ catheter. Independent significant predictors for EVD-related hemorrhage were the preoperative prescription of aspirin (adjusted OR 1.94; 95% CI 1.10-3.44), catheter malposition (aOR 1.99; 95% CI 1.22-3.23), and use of the 2.8-mm Medtronic™ catheter (aOR 4.22; 95% CI 2.39-7.41). CONCLUSIONS: The per-catheter risk of hemorrhage was 8.1%, but the incidence of symptomatic hemorrhage was low. The only patient risk factor was aspirin intake. This is the first study to evaluate and establish an association between catheter malposition and catheter design with EVD-related hemorrhage.

Species separation of a binary mixture under acoustic streaming.

An analytical and numerical study of the action of ultrasonic waves on species separation within a rectangular cavity filled with a binary fluid (water-ethanol mixture) is presented. An ultrasonic wave was emitted on a portion of one of its vertical walls, while the opposite wall was perfectly absorbent. The two horizontal walls were differentially heated. A progressive acoustic wave was used to generate, at a large scale, a stationary flow of the viscous binary fluid (Eckart Streaming) within the cavity. The authors analytically determined the temperature T, mass fraction C and velocity fields under the parallel flow hypothesis used for cells with high aspect ratio [Formula: see text], in the presence of the gravitational field. From the analysis of the velocity fields the authors concluded that the associated flow is either unicellular or consists of three counter-rotating cells superimposed in the horizontal direction of the cavity. They also found the variation domains of the physical parameters leading to one or the other of these two types of flows. The algebraic equation allowing the calculation of the mass fraction gradient and hence the species separation between the vertical walls of the cavity was determined. The variation of the dimensional mass fraction gradient, for the water-ethanol mixture, as a function of the two control parameters of the problem, namely the acoustic parameter A and the temperature difference [Formula: see text] imposed on the two horizontal walls was studied.

[Impact of the 2009 Afssaps guidelines on the management of venous thromboembolic disease in emergency department: Before/after study]. / Impact des recommandations Afssaps 2009 sur la prise en charge de la maladie thromboembolique veineuse aux urgences : étude avant/après.

INTRODUCTION: The French Agency for Health Safety of Products published recommendations of good practices (RGP) for the treatment of venous thromboembolic disease in 2009. Four of these recommendations apply to the initial management of the disease, with the objective of this study is to determine whether the development and diffusion of the four RGP has had an impact on the practice. METHODS: A retrospective before/after study comparing 132 patients treated in emergency department of the Civil Hospices of Lyon for pulmonary embolism (PE) and/or deep venous thrombosis (DVT) in 2008-2009 ("before") and 153 patients in 2010-2011 ("after"). RESULTS: In the "before" period, 70 patients were treated for DVT and 62 patients for PE. In the "after" period, 50 patients were treated for DVT and 103 patients for PE. The compliance rate was not significantly different for the two periods for each RGP except for the indication of low molecular weight Heparin (LMWH) or fondaparinux in the absence of severe renal failure (21% "before" vs. 45% "after"; P=0.02) for patients with PE. Management for the four recommendations was conform for 5.6% of eligible patients in the "before" period and for 3.7% for the "after" period. CONCLUSION: Our study shows that globally there is no impact of RGP. The reasons appear multiple with first, the mere dissemination and the absence of implementation of these guidelines.

Selective focusing through target identification and experimental acoustic signature extraction: Numerical experiments.

Using transducer arrays and appropriate emission delays allow to focus acoustic waves at a chosen location in a medium. The focusing spatial accuracy depends on the accurate knowledge of its acoustic properties. When those properties are unknown, methods based on the Time-Reversal principle allow accurate focusing. Still, these methods are either intrusive (an active source has to be introduced at the target location first), either blind (the target cannot be selected in the presence of several objects.) The purpose of the present work is to achieve non-invasive accurate focusing on a selected target using inaccurate acoustic properties for the investigated medium. Potential applications are for instance noninvasive surgery based on High Intensity Focused Ultrasound (HIFU). Numerical experiments are presented and demonstrate accurate focusing on a previously designated target located in an unknown heterogeneous medium.

Origin of a Non-Clarke's Column Division of the Dorsal Spinocerebellar Tract and the Role of Caudal Proprioceptive Neurons in Motor Function.

Proprioception, the sense of limb and body position, is essential for generating proper movement. Unconscious proprioceptive information travels through cerebellar-projecting neurons in the spinal cord and medulla. The progenitor domain defined by the basic-helix-loop-helix (bHLH) transcription factor, ATOH1, has been implicated in forming these cerebellar-projecting neurons; however, their precise contribution to proprioceptive tracts and motor behavior is unknown. Significantly, we demonstrate that Atoh1-lineage neurons in the spinal cord reside outside Clarke's column (CC), a main contributor of neurons relaying hindlimb proprioception, despite giving rise to the anatomical and functional correlate of CC in the medulla, the external cuneate nucleus (ECu), which mediates forelimb proprioception. Elimination of caudal Atoh1-lineages results in mice with relatively normal locomotion but unable to perform coordinated motor tasks. Altogether, we reveal that proprioceptive nuclei in the spinal cord and medulla develop from more than one progenitor source, suggesting an avenue to uncover distinct proprioceptive functions.

[Development of a tool for withholding and withdrawing life-sustaining treatment in the emergency room]. / Élaboration et validation d'une fiche d'aide à la décision de limitation ou d'arrêt des traitements aux urgences.

OBJECTIVES: Active treatment withholding and withdrawing decisions in the emergency room (ER) must be taken collegially according to ethical and juridical statements. Specific tools can support this process and our main goal was to create and validate such a tool. METHOD: We created a first version of a tool to help for treatment withholding and withdrawing decisions inspired by similar documents from literature. Every item of this tool was then assessed by a group of experts (ER physicians and nurses) using the Delphi method to reach a consensus. RESULTS: Thirty-four experts from eleven ER (academic, regional centre) were included and participate to the first round and twenty-seven to the second round. From the eighty-two-item tool, sixty-five items reach a consensus during these two rounds and were kept to constitute the final version of the tool. CONCLUSION: We have been able to create a tool to help for treatment withholding and withdrawing decisions adapted to the guidelines for end of life patient's management in the ER. This tool has been validated using a Delphi method by a group of experts from different centres. This multicentre validation will help for the diffusion and use of this tool in the different ER of the Rhône-Alpes region.

Acoustic probing of the jamming transition in an unconsolidated granular medium.

Experimentally determined dispersion relations for acoustic waves guided along the mechanically free surface of an unconsolidated granular packed structure provide information on the elasticity of granular media at very low pressures that are naturally controlled by the gravitational acceleration and the depth beneath the surface. The experiments confirm recent theoretical predictions that relaxation of the disordered granular packing through nonaffine motion leads to a peculiar scaling of shear rigidity with pressure near the jamming transition corresponding to zero pressure.

[Evaluation of functional capability after hospital admission of nonagenarian patients]. / Valoración de la capacidad funcional después de un ingreso hospitalario en pacientes nonagenarios.

BACKGROUND: Hospitalisation in nonagenarians patients may causes functional decline. PATIENTS AND METHOD: The study sample included all nonagenarians patients admitted during three months in two teaching hospitals. RESULTS: We studied 125 patients (24 [19%] died). In the remaining 101 patients the previous Barthel index (BI) was 75, at admission 33 (p < 0.0001), and at discharge 43 (p < 0.001). The decline in BI at discharge was remarkable ( 32; p < 0.0001) and persisted after 3 months (12, p < 0.003). CONCLUSION: After three months of hospitalisation in nonagenarians patients persist a functional decline.