Cadmium-Induced Renal Cell Toxicity Is Associated With MicroRNA Deregulation.

Cadmium is an environmental pollutant well known for its nephrotoxic effects. Nevertheless, mechanisms underlying nephrotoxicity continue to be elucidated. MicroRNAs (miRNAs) have emerged in recent years as modulators of xenobiotic-induced toxicity. In this context, our study aimed at elucidating whether miRNAs are involved in renal proximal tubular toxicity induced by cadmium exposure. We showed that cadmium exposure, in 2 distinct renal proximal tubular cell models (renal proximal tubular epithelial cell [RPTEC]/human telomerase reverse transcriptase [hTERT] and human kidney-2), resulted in cytotoxicity associated with morphological changes, overexpression of renal injury markers, and induction of apoptosis and inflammation processes. Cadmium exposure also resulted in miRNA modulation, including the significant upregulation of 38 miRNAs in RPTEC/hTERT cells. Most of these miRNAs are known to target genes whose coding proteins are involved in oxidative stress, inflammation, and apoptosis, leading to tissue remodeling. In conclusion, this study provides a list of dysregulated miRNAs which may play a role in the pathophysiology of cadmium-induced kidney damages and highlights promising cadmium molecular biomarkers that warrants to be further evaluated.

Impact of localisation of deep brain stimulation electrodes on motor and neurobehavioural outcomes in Parkinson's disease.

BACKGROUND: Deep brain stimulation (DBS) of the subthalamic nucleus (STN) represents a well-established treatment in advanced Parkinson's disease (PD) for motor signs, but it is still debated concerning psychiatric effects. OBJECTIVE: Exploration of relation between position of active electrode contacts and neuropsychological and motor change after STN DBS procedure for PD. METHODS: A cohort of 34 patients who underwent STN DBS was followed for 6 months. Preoperative and postoperative assessments included mood evaluation (depression and mania) and motor status. Active contact localisation was identified regarding position into the STN (4 groups: IN meant contacts were IN-IN IN-BORDER; OUT: OUT-OUT or OUT-BORDER; BORDER: BORDER-BORDER; IN-OUT: IN-OUT) and compared with clinical outcomes. RESULTS: STN DBS significantly improved motor scores and reduced dopaminergic medication when compared with baseline and active lead groups: the best result was seen with the IN group. At 3 and 6 months postsurgery, depression and manic scores do not significantly differ compared with baseline and between leads groups. Focusing on symptom domains and compared with baseline, a significant loss of appetite was observed for the IN group at M3 and a significant increase in appetite from baseline was observed at M3 for the OUT group. Graphic representations illustrate that postsurgery evolution parameters at M3 or M6 are very good discriminant variables and well differentiate all leading groups. CONCLUSIONS: Stimulation of zona incerta may influence appetite and weight gain. Our clinical results seem to support a personalised DBS-targeted Parkinson therapy including individual motor and non-motor parameters.

Observation of a new electronic state of CO perturbing W ¹Π(v=1).

We observe photoabsorption of the W(1) ← X(0) band in five carbon monoxide isotopologues with a vacuum-ultraviolet Fourier-transform spectrometer and a synchrotron radiation source. We deduce transition energies, integrated cross sections, and natural linewidths of the observed rotational transitions and find a perturbation affecting these. Following a deperturbation analysis of all five isotopologues, the perturbing state is assigned to the v = 0 level of a previously unobserved (1)Π state predicted by ab initio calculations to occur with the correct symmetry and equilibrium internuclear distance. We label this new state E″ (1)Π. Both of the interacting levels W(1) and E″(0) are predissociated, leading to dramatic interference effects in their corresponding linewidths.

Adenocarcinoma arising in gastric heterotopic pancreas. Case report and review of the literature.

A sixty years-old patient was admitted with a gastric tumor corresponding to an adenocarcinoma developed in ectopic pancreatic tissue. Hundred cases of gastric heterotopic pancreas are shown in literature. This entity may remain asymptomatic. Symptoms such abdominal pain are described as the result of tumour growth. Carcinogenesis of ectopic pancreas (EPa) is however rare. Diagnosis is rarely pre-operative because modern imaging depicts a gastric tumour with no more information. The only treatment is surgery, with a best interest in frozen sections to direct the procedure, in this case a total gastrectomy with D2 lymphadenectomy. Based on this case report, an analysis of the literature focusing on diagnosis and treatment is presented.

Demonstration for cold atmospheric pressure plasma jet operation and antibacterial action in microgravity.

Cold atmospheric pressure plasma (ionized gas) is an innovative medical tool for the treatment of infected wounds thanks to its potential to inactivate drug-resistant microorganisms and promote tissue regeneration and vascularization. The low power consumption, compactness, and versatility of Cold Atmospheric Pressure Plasma (CAPP) devices make them an ideal tool for risk mitigation associated with human spaceflights. This work presents results in microgravity on the operability of CAPP and its antimicrobial effect. The experiments carried out in parabolic flights make it possible to optimize the treatment conditions (i.e., the distance, the gas mixture) and to obtain the rapid inactivation (<15 s) of Escherichia coli samples. Interestingly, the inactivation efficiency of CAPP was higher during parabolic flights than under terrestrial conditions. Overall, these results encourage the further development of CAPP medical devices for its implementation during human spaceflights.

[Frameless trigeminal neuralgia radiosurgery with a dedicated linear accelerator: From equipment commissioning to initial clinical results]. / Radiochirurgie des névralgies trigéminales avec accélérateur linéaire dédié sans cadre invasif : de la mise en service de l'appareil aux premiers résultats cliniques.

PURPOSE: Radiosurgery for the treatment of trigeminal neuralgia delivers a very high dose in a single fraction, over a few millimeters, at a single isocenter placed along the nerve. We present here the different steps that have been performed to validate small beams by conical collimators, and report the clinical results of the first patients treated on Novalis Tx®, frameless. MATERIAL AND METHODS: First, the geometric accuracy of 4 and 6mm conical collimators was evaluated using Winston-Lutz tests; then dosimetric data acquisition was performed using high spatial resolution detectors (PTW 60019 microdiamond and a PTW 60017 E-diode). The corrective factors of the TRS 483 report were applied to calculate the collimator aperture factors. These dosimetric data were then compared with the data implemented in the iPlan® treatment planning system. Then end-to-end tests were performed to control the entire treatment process using an anthropomorphic phantom "STEEV". Between 2020 and 2022, 18 patients were treated for refractory trigeminal neuralgia on Novalis Tx®, frameless, with Exactrac® repositioning. A total of 17 patients were evaluated (one was lost to follow-up) using the BNI score for pain assessment and MRI with a median follow-up of 12 months. RESULTS: The quality criteria of geometric and dosimetric accuracy were met for the 6-mm cone but not for the 4-mm cone. All patients were treated with a 6-mm cone with a dose of 90Gy prescribed at the isocenter at the root entry zone. Initial pain control was obtained in 70.5% of our patients, and 53% maintained pain control with a median follow-up of 12 months. All recurrences occurred within 3 to 6 months after radiosurgery. No brainstem toxicity was observed. Six patients had non-disabling facial hypoesthesia, half of whom already had pretreatment hypoesthesia. CONCLUSION: The treatment of trigeminal neuralgia on a dedicated linear accelerator is a highly technical treatment whose accuracy and safety are paramount. The physical measurements allowed the commissioning of the technique with a 6mm cone. Our first clinical results are in accordance with the literature.

Water formation through O2 + D pathway on cold silicate and amorphous water ice surfaces of interstellar interest.

The formation of the first monolayer of water molecules on bare dust grains is of primary importance to understand the growth of the icy mantles that cover dust in the interstellar medium. In this work, we explore experimentally the formation of water molecules from O(2) + D reaction on bare silicate surfaces that simulates the grains present in the diffuse interstellar clouds at visual extinctions (A(V) < 3 mag). For comparison, we also study the formation of water molecules on surfaces covered with amorphous water ice representing the dense clouds (A(V) ≥ 3 mag). Our studies focus on the formation of water molecules in the sub-monolayer and monolayer regimes using reflection absorption infrared spectroscopy and temperature-programmed desorption techniques. We provide the fractions of the products, such as D(2)O and D(2)O(2) molecules formed on three astrophysically relevant surfaces held at 10 K (amorphous olivine-type silicate, porous amorphous water ice, and nonporous amorphous water ice). Our results showed that the formation of D(2)O molecules occurs with an efficiency of about 55%-60% on nonporous amorphous water ice and about 18% on bare silicate grains surfaces. We explain the low efficiency of D(2)O water formation on the silicate surfaces by the desorption upon formation of certain products once the reaction occurs between O(2) and D atoms on the surface. A kinetic model taking into account the chemical desorption of newly formed water supports our conclusions.

Neural correlates of consciousness and related disorders: From phenotypic descriptors of behavioral and relative consciousness to cortico-subcortical circuitry.

We report a review of medical aspects of the consciousness. The behavioral dimension, phenotypic descriptors, relative consciousness and neural correlates of consciousness and related disorders were addressed successively in a holistic and chronological approach. Consciousness is relative, specific to each individual across time and space. Historically defined as the perception of the self and the environment, it cannot be separated from behaviors, entailing an idea of conscious behavior with metapractic and metagnostic aspects. Observation of spontaneous and evoked overt behavior distinguishes three main types of disorder of consciousness (DoC): coma, vegetative state or unresponsive wakefulness, and minimally conscious or relationally impoverished state. Modern functional exploration techniques, such as imaging, increase the understanding of DoCs and consciousness. Whether consciousness is a superior function and/or an instrumental function is discussed. Neural correlates can be subdivided into two wakefulness pathways (superior thalamic cholinergic and inferior extra-thalamic), and cortico-subcortical circuitry. The deep brain structures are those described in the well-known sensorimotor, associative and limbic loops, as illustrated in the mesolimbic model of DoC. The cortices can be segregated into several overlapping networks: (1) a global workspace including thalamo-cortical loops; (2) the default mode network (DMN) and related intrinsic connectivity networks (i.e., central executive, medial DMN and salience networks); (3) a 3-fold network comprising the fronto-parietal control system and its dorsal and ventral attentional sub-networks, the fronto-parietal executive control network, and the cingulo-opercular salience network; (4) the internal and external cortices, respectively medial, turned toward the self, and lateral, turned toward the environment. The network dynamics is the reflection of consciousness, notably anticorrelations such as the decrease in activity of the posterior cingulate-precuneus regions during attentional tasks. Thanks to recent advances in DoC pathophysiology, further significative therapeutic progress is expected, taking into account the societal context. This depends notably on the dissemination of medical knowledge and its transfer to a wider public.

Nuclear spin conversion of molecular hydrogen on amorphous solid water in the presence of O2 traces.

Nuclear spin conversion (NSC) of ortho- to para-H(2) and para- to ortho-D(2) has been investigated on an amorphous solid water (ASW) surface at 10 K, in the presence of co-adsorbed O(2). The dynamics of the nuclear spin conversion could be revealed by combination of resonance enhanced multiphoton ionization spectroscopy (REMPI) with temperature programmed desorption (TPD) experiments. The conversion rates are consistent with a diffusion of molecular hydrogen inducing a nuclear spin conversion enhanced in the vicinity of molecular oxygen. The conversion times were found to increase with decreasing O(2) and H(2) coverage. Finally, on oxygen free ASW surface, the extremely long conversion characteristic times measured showed that such surface is not an efficient catalyst for NSC, in contradiction with hypothesis commonly made for interstellar medium.

Misleading clinical presentation of carcinoid syndrome.

Rare cases of carcinoid syndromes can develop from either gastrointestinal neuroendocrine tumors (NETs) without liver metastasis or large retroperitoneal involvement. We report a case of a patient with isolated flushing highly suggestive of carcinoid syndrome caused by an ileal NET with adjacent lymph node metastases but with no liver metastases. The final diagnose was delayed for this patient due to a combination of misleading clinical presentation and negative usual screening tests (urinary 5-HIAA and serum chromogranine A). Given its high sensitivity and specificity, 68Ga-DOTATATE PET/CT confirmed the diagnosis of neuroendocrine tumor. Therefore, this case reminds clinicians that carcinoid syndrome may manifest as flushing only and highlights that imaging is a major aspect of the evaluation and diagnosis of patients with suspected gastrointestinal NETs.

Functional and dysfunctional impulsivities changes after subthalamic nucleus-deep brain stimulation in Parkinson disease.

OBJECTIVES: We investigated changes of impulsivity after deep brain stimulation (DBS) of the subthalamic nucleus (STN) in Parkinson's disease (PD) patients, distinguishing functional from dysfunctional impulsivity and their contributing factors. METHODS: Data of 33 PD patients treated by STN-DBS were studied before and 6 months after surgery: motor impairment, medication (dose and dopaminergic agonists), cognition, mood and occurrence of impulse control disorders. Impulsivity was assessed by the Dickman Impulsivity Inventory, which distinguishes functional impulsivity (FI), reflecting the potential for reasoning and rapid action when the situation requires it, and dysfunctional impulsivity (DI), reflecting the lack of prior reasoning, even when the situation demands it. The location of DBS leads was studied on postoperative MRI using a deformable histological atlas and by compartmentalization of the STN. RESULTS: After STN-DBS, DI was significantly increased (mean pre- and postoperative DI scores 1.9±1.6 and 3.5±2.4, P<0.001) although FI was not modified (mean pre- and postoperative FI scores 6.2±2.7 and 5.8±2.6). Factors associated with a DI score's increase≥2 (multivariable logistic regression model) were: low preoperative Frontal Assessment Battery score and location of the left active contact in the ventral part of the STN. CONCLUSION: Our study suggests that STN-DBS may have a different impact on both dimensions of impulsivity, worsening pathological impulsivity without altering physiological impulsivity. The increase in dysfunctional impulsivity may be favoured by the location of the electrode in the ventral part of the STN.

Gas temperature dependent sticking of hydrogen on cold amorphous water ice surfaces of interstellar interest.

Using the King and Wells method, we present experimental data on the dependence of the sticking of molecular hydrogen and deuterium on the beam temperature onto nonporous amorphous solid water ice surfaces of interstellar interest. A statistical model that explains the isotopic effect and the beam temperature behavior of our data is proposed. This model gives an understanding of the discrepancy between all known experimental results on the sticking of molecular hydrogen. Moreover, it is able to fit the theoretical results of Buch et al. [Astrophys. J. 379, 647 (1991)] on atomic hydrogen and deuterium. For astrophysical applications, an analytical formula for the sticking coefficients of H, D, H(2), D(2), and HD in the case of a gas phase at thermal equilibrium is also provided at the end of the article.

[Functional stereotactic radiosurgery: Indications and perspectives]. / Radiochirurgie fonctionnelle : indications et perspectives.

Stereotactic radiosurgery (SRS) is a non-invasive technique that enables to create brain focal lesions with a high precision and localization. Thus, functional brain disorders can be treated by SRS in case of pharmacoresistance or inoperability. To date, treatment of trigeminal neuralgia is the most described and known indication. Other indications will be developed in the future like movement disorders, refractory epilepsy, obsessive compulsive disorder and severe depression. We present here a review of actual and future indications of functional brain SRS with their level of evidence. All these SRS treatments have to be strictly conducted by trained teams with an excellent collaboration between radiation physicists, medical physicists, neurosurgeons, neurologists, psychiatrists and probably neuroradiologists.

Postoperative empyema following chronic subdural hematoma surgery: Clinically based medicine.

INTRODUCTION: Subdural empyema (SDE) is a rare complication of chronic subdural hematoma (CSDH) surgery. We introduced antibiotic prophylaxis (AP) for this procedure in 2014 following a morbidity-mortality conference (MMC) in our department. We report the results of retrospective data analysis to assess the effect of systematic AP and to identify risk factors for SDE. MATERIAL AND METHODS: Two hundred eight patients were recruited between January 2013 and December 2015; 5 were excluded for incomplete data: 107 without and 96 with AP (n=203). SDE was confirmed by clinical examination, imaging and bacteriological analysis. Comparisons between AP-(no cefuroxime) and AP+ (cefuroxime) groups were made with Chi2 test and Student's t-test. RESULTS: One empyema was found in each group, indicating that AP had no effect (P=1). The only criterion associated with SDE for these two patients was a greater number of reoperations for CSDH recurrence (P=0.013). DISCUSSION: The incidence of postoperative empyema was 1%, similar to the range of 0.2%-2.1% reported in the literature. This rare incidence explains why we found no significant effect of AP. The medical decision taken at the MMC did not help to reduce the rate of postoperative SDE. MMCs can help to define factors associated with adverse surgical events and identify opportunities for improvement. CONCLUSION: AP, introduced after an MMC, did not impact SDE rates. In practice, AP should be required only in case of reoperation for CSDH recurrence. However, we still continue to use AP following the MMC considering different parameters discussed in the manuscript.

Assessment of Maturational Changes in White Matter Anisotropy and Volume in Children: A DTI Study.

BACKGROUND AND PURPOSE: Anisotropy is a good indicator of white matter fascicle macrostructure and organization but the interpretation of its changes with age remains difficult. The increase of WM fascicle fractional anisotropy with time and its relationship with WM fascicle volume have never been examined during childhood. We studied the maturation of associative WM fascicles during childhood using MR imaging-based DTI. We explored whether the fractional anisotropy increase of the main WM fascicles persists beyond the period of brain growth and is related to WM fascicle volume increase. MATERIALS AND METHODS: In a series of 25 healthy children, the fractional anisotropy and volume of 15 associative WM fascicles were calculated. Several regression linear mixed models were used to study maturation parameters (fractional anisotropy, volume, and total telencephalon volume) considered as dependent variables, while age and sex were independent variables (the variable identifying the different WM fascicles was considered as a repeated measure). RESULTS: In children older than 8 years of age, WM fascicle fractional anisotropy increased with age (P value = .045) but not its volume (P value = .7) or the telencephalon volume (P value = .16). The time course of WM fascicle fractional anisotropy and volume suggested that each WM fascicle might follow a specific pattern of maturation. CONCLUSIONS: The fractional anisotropy increase of several WM fascicles after 8 years of age may not result from an increase in WM fascicle volume. It might be the consequence of other developmental processes such as myelination.

Long-Term Outcomes After Linac Radiosurgery for Benign Meningiomas.

AIMS: Although several studies on outcomes following stereotactic radiosurgery (SRS) for benign meningiomas have been reported, Linac-based SRS outcomes have not been as widely evaluated. The aim of this retrospective institutional single-centre study was to determine long-term outcomes of Linac-based SRS for benign intracranial meningiomas. MATERIALS AND METHODS: From July 1996 to May 2011, 60 patients with 69 benign meningiomas were included. All patients were treated with single-fraction Linac-based SRS with four to five non-coplanar arcs, dynamic or not. The marginal dose prescribed for the periphery was 16 Gy. Prognostic factors associated with local control, progression-free survival (PFS) and overall survival were tested. RESULTS: The median follow-up was 128 months. No patient was lost to follow-up. The values observed at 1, 5 and 10 years were, respectively, 100%, 98.4% and 92.6% for local control, 94.9%, 93.2% and 78% for PFS and 100%, 94.7% and 92.7% for overall survival. In univariate analysis, local control after SRS was significantly higher for skull base and parasagittal meningiomas compared with convexity meningiomas (P = 0.031). Multivariate analyses showed significantly longer PFS when the minimum dose delivered to the tumour was greater than 10 Gy (P = 0.0082). No grade 5 toxicity was reported. CONCLUSION: Our long-term results from a large sample size of benign meningiomas treated with Linac-based SRS confirmed excellent local control (>90%) and good safety, which is in line with published studies on Gamma Knife surgery. Above all, we showed significantly poorer PFS if the minimum dose to the tumour was under 10 Gy.

New electrophysiological mapping combined with MRI in parkinsonian's subthalamic region.

The subthalamic nucleus (STN) is the main target for deep brain stimulation in Parkinson's disease. We analysed the relationships between magnetic resonance imaging (MRI) anatomy and spontaneous neuronal activity to confirm the potential of microelectrode recordings to assist in determining the optimal surgical target. Ten bilateral surgeries were performed after 1.5-T (T2-weighted) anatomical MRI identification of the STN, zona incerta (ZI), Forel's field H2 (H2) and substantia nigra (SN). Spontaneous neuronal activity was recorded simultaneously along the distal 10 mm on a central track (optimally covering the STN) and a 2-mm anterior track. We calculated off-line mean firing rate and burst frequency on 248 neurons clustered according to anatomical structure. Subjective visual analysis of signal was also realized on-line, during surgery, to classify patterns of activity. Mean firing rate and burst frequency increased from H2-ZI to SN. The mean firing rate was higher in SN only using paired comparison (SN vs. its neighbours). The burst frequency was lower in H2 than in SN; using comparison with neighbours, it was lower in H2 and ZI. An irregular high activity (type 2C) was more often detected in STN and SN than in H2 and ZI. Anatomical boundaries and unitary recordings appear to be linked, supporting the ability of MRI to provide a detailed anatomy. Electrophysiological mapping combined with MRI is a useful tool for precise targeting in the subthalamic region.

Overweight after deep brain stimulation of the subthalamic nucleus in Parkinson disease: long term follow-up.

OBJECTIVE: To assess the occurrence of weight gain in patients with Parkinson's disease, with an average 16 months of follow-up after subthalamic nucleus deep brain stimulation. METHODS: We used dual x ray absorptiometry to evaluate changes in body weight and body composition in 22 patients with Parkinson's disease (15 men and seven women) before surgery, 3 months after surgery and on average 16 months after surgery. RESULTS: No patient was underweight before surgery and 50% were overweight. By contrast, 68% were overweight or obese 3 months after surgery and 82% after 16 months (p<0.001). For men, the mean increase in body mass index (BMI) was 1.14 (0.23) kg/m(2) 3 months after surgery and 2.02 (0.36) kg/m(2) 16 months after surgery. For women, the mean increases in BMI at the same evaluation times were 1.04 (0.30) kg/m(2) and 2.11 (0.49) kg/m(2). This weight gain was mainly secondary to an increase in fat mass in both men and women. Three months after surgery, acute subthalamic deep brain stimulation induced an improvement in parkinsonian symptoms (evaluated by the Unified Parkinson Disease Rating Scale (UPDRS) part III) by 60.7 (2.9)% in the "off" dopa condition and a dramatic improvement of motor complications (dyskinesia duration: 82.8 (12.8)%, p<0.0001; off period duration: 92.7 (18.8)%, p<0.0001). CONCLUSION: Although subthalamic nucleus deep brain stimulation significantly improved parkinsonian symptoms and motor complications, many patients became overweight or obese. This finding highlights the necessity to understand the underlying mechanisms and to provide a diet management with a physical training schedule appropriate for patients with Parkinson's disease.

Structural characterization by IRMPD spectroscopy and DFT calculations of deprotonated phosphorylated amino acids in the gas phase.

Gas-phase infrared spectra of deprotonated phosphorylated amino acids ([pAA-H](-))-phosphoserine ([pSer-H](-)), phosphothreonine ([pThr-H](-)), and phosphotyrosine ([pTyr-H](-))-and of the dihydrogen phosphate anion H(2)PO(4)(-) have been recorded in the mid-IR region (650-2000 cm(-1)) under tandem mass spectrometry conditions. The experimental setup involved a Paul ion trap equipped with an electrospray ionization source coupled with a tunable free electron laser (FEL). Spectral assignment of the observed IRMPD bands and identification of the vibrational signatures of the phosphorylation have been performed by comparison with DFT calculations. The H(2)PO(4)(-) anion has been used as a simple model of a free deprotonated phosphate group, helping the identification of the IR signatures of phosphorylation. Our results show that deprotonation occurs on the phosphate group for the three amino acids. A comparison between the deprotonated and protonated phosphorylated amino acids is reported for the most important vibrational features.

Infrared multiphoton electron detachment spectroscopy of C76(2-).

In this letter, we report the first infrared spectrum of C(76)(2-). This multiply charged anion has been studied in an electrodynamic ion trap held at room temperature using tunable infrared radiation from a free-electron laser. Resonant vibrational excitation is found to cause electron detachment and the resulting singly negatively charged as well as the remaining doubly charged parent ion are monitored as a function of IR wavelength in an experimental scheme that we term infrared multiphoton electron detachment spectroscopy. The obtained IR spectra are contrasted to computed vibrational spectra using density functional theory. The dianionic molecule retains its overall symmetry (i.e., D(2) point group) with a (1)A(1) ground state with respect to the neutral fullerene. Spectral shifts of characteristic tangential modes relative to the neutral cage are shown to originate from the excess charge density.