Human pegivirus identified in severe myelitis and optic neuritis in immunocompromised patients: A pathogenic role for a forgotten virus?

The role of Human pegivirus (HPgV) in patients with encephalitis has been recently questioned. We present cases of 4 patients with similar clinical, biological, and radiological characteristics, including a past history of transplantation with long-term immunosuppression and a progressive course of severe and predominantly myelitis, associated in 3 cases with optic neuropathy causing blindness. Extensive workup was negative but analysis of the CSF by use of pan-microorganism DNA- and RNA-based shotgun metagenomics was positive for HPgV. This case series further supports the hypothesis of HPgV CNS infection and highlights the utility of metagenomic next-generation sequencing of CSF in immunocompromised patients.

Methoxpropamine (MXPr) in powder, urine and hair samples: Analytical characterization and metabolite identification of a new threat.

Methoxpropamine (MXPr) is an arylcyclohexylamine dissociative drug with structural similarities with 3-MeO-PCE, ketamine and deschloroketamine. MXPr was identified for the first time in Europe in October 2019 in Denmark and is considered a new psychoactive substance. We undertook the molecular identification and characterization of MXPr in urine, hair and powder samples. We used a combination of several analytical methods: liquid-state nuclear magnetic resonance (NMR), infra-red spectroscopy (IR) and liquid chromatography high-resolution mass spectrometry (LC-HRMS). The second objective was to explore the metabolism of MXPr in silico and in vitro. To detect characteristic metabolites that prove MXPr consumption by urine analysis, pooled human liver microsome (pHLM) assays were performed and evaluated using liquid chromatography quadrupole time-of-flight mass spectrometry (LC-QToF-MS). A software algorithm (Unifi®) was used to predict in silico biotransformations of MXPr. Three metabolites were identified in the in vitro studies including N-despropyl(nor)MXPr, O-desmethyl MXPr and dihydroMXPr. Most of these phase II metabolites were confirmed to be present in urine and hair samples collected from an MXPr consumer. This is the first report of the identification of MXPr in France with analytical findings. This study highlights the challenge of identifying new psychoactive substances (NPS) when they are missing from compound libraries and if a standard is not available. The use of various complementary analytical methods combined with HRMS offers a promising approach for the molecular characterization of NPS.

Early successful reperfusion after endovascular therapy reduces malignant middle cerebral artery infarction occurrence in young patients with large diffusion-weighted imaging lesions.

BACKGROUND AND PURPOSE: Malignant middle cerebral artery infarction (MMI) is a severe complication of acute ischaemic stroke (AIS). The aim of our study was to assess whether successful reperfusion after endovascular therapy (EVT) in AIS with clinical and imaging predictors of MMI decreased its occurrence. METHODS: Data were collected between January 2014 and July 2018 in a monocentric prospective AIS registry of patients treated with EVT. Patients selected were <65 years old with severe anterior circulation AIS with a National Institutes of Health Stroke Scale score >15, baseline Diffusion-Weighted Imaging-Alberta Stroke Program Early Computed Tomography Score ≤ 6 and baseline diffusion-weighted imaging lesion volume >82 mL within 6 h of symptom onset. Successful reperfusion was defined as a Thrombolysis in Cerebral Ischemia score ≥ 2b. Occurrence of MMI was the primary endpoint. RESULTS: A total of 66 EVT-treated patients were included in our study. MMI occurred in 27 patients (41%). In unadjusted analysis, successful reperfusion was associated with fewer MMIs (31.8% vs. 65.0%; P = 0.015) and with more favorable outcome at 3 months (50% vs. 20%; P = 0.023). In multivariate analysis, successful reperfusion was associated with an adjusted odds ratio (95% confidence intervals) of 0.35 (0.10-1.12) for MMI and 2.77 (0.84-10.43) for 3-month favorable outcome occurrence. CONCLUSIONS: Early successful reperfusion performed in patients with AIS with clinical and imaging predictors of MMI was associated with decreased MMI occurrence. Reperfusion status might be considered in evaluating the need for craniectomy in patients with early predictors of MMI.

(19)F NMR monitoring of the eukaryotic 20S proteasome chymotrypsin-like activity: an investigative tool for studying allosteric regulation.

The proteasome displays three distinct proteolytic activities. Currently, proteasome inhibitors are evaluated using specific fluorescent substrates for each of the individual active sites. However, the photophysical properties of the commonly used fluorophores are similar and thus, the simultaneous monitoring of the three proteolytic activities is not possible. We have developed a bimodal fluorescent fluorinated substrate as a novel tool to study the chymotrypsin-like (ChT-L) proteolytic activity and its regulation by inhibitors and by substrates of trypsin-like (T-L) and caspase-like sites (PA). We demonstrate that this substrate is reliable to evaluate the ChT-L inhibitory activity of new molecules either by fluorescence or (19)F NMR spectroscopy. We have found that the ChT-L activity is dramatically reduced in the presence of T-L and PA substrates. This work provides a proof of concept that the fluorinated substrate enables investigation of the allosteric regulation of the ChT-L activity.

Influence of polymer end-chemistry on the morphology of perfluorohexane polymeric microcapsules intended as ultrasound contrast agents.

Ultrasound contrast agents (UCAs) composed of a liquid perfluorocarbon (PFC) core surrounded by a polymer shell have shown promising echogenicity as well as stability. In a strategy to optimize the ultrasound properties of these systems, encapsulating a liquid PFC with a low boiling point such as perfluorohexane (PFH) was suggested. The ultimate aim of these systems would be to induce phase-transition of the liquid PFH into gas by acoustic droplet vaporization (ADV) to further increase the UCA acoustic response. Microcapsules with a perfluorohexane core have been developed by an emulsion-evaporation process, using three biodegradable polymers: PLGA and PLA with acid (PLA-COOH) and ester (PLA-COOR) terminations. Despite their similar properties, these polymers were found to strongly influence the final microcapsule morphology. While PLGA was able to form nice core-shell microcapsules, the use of PLA-COOH led to decentered microcapsules and big "eye" morphologies, and PLA-COOR induced the formation of "acorn" morphologies. To shed light on morphologies disparities, polymer interfacial behavior was studied at the dichloromethane-water and the PFH-dichloromethane interfaces. One can conclude that the core-shell structure is the result of a significant adsorption of the polymer at the dichloromethane-water interface together with a good stability of the PFH droplet within the emulsion globule. Previous work has shown that the capsule's thickness-to-radius (T/R) ratio can be controlled easily by varying the polymer to perfluorocarbon proportions. This versatility was confirmed for PFH capsules with PLA-COOH and PLGA shells. Finally, the encapsulation efficiency of PFH was assessed by relating the T/R ratio to the volume fraction of PFH and by (19)F NMR spectroscopy.

[Dosimetric and clinical benefits of respiratory-gated radiotherapy for lung and breast cancers: results of the STIC 2003]. / Intérêts dosimétriques et cliniques de la radiothérapie asservie à la respiration des cancers du poumon et du sein : résultats du Stic 2003.

PURPOSE: To compare respiratory-gated conformal radiotherapy versus conventional conformal radiotherapy for the irradiation of non-small cells lung cancer and breast cancer. PATIENTS AND METHODS: The STIC 2003 project was a comparative, non-randomized, multicenter and prospective study that included in 20 French centers between April 2004 and June 2008, 634 evaluable patients, 401 non-small cells lung cancer and 233 breast cancers. RESULTS: The final results confirmed the feasibility and good reproducibility of the various respiratory-gated conformal radiotherapy systems regardless of tumour location. The results of this study demonstrated a marked reduction of dosimetric parameters predictive of pulmonary, cardiac and esophageal toxicity, especially for non-small cells lung cancer, as a result of the various respiratory gating techniques. These dosimetric benefits were mainly observed with deep inspiration breath-hold techniques (ABC and SDX), which markedly increased the total lung volume compared to the inspiration-synchronized system based on tidal volume (RPM). For non-small cells lung cancer, these theoretical dosimetric benefits were correlated with a significant reduction in clinically acute and late toxicities, especially the pulmonary. For breast cancer, although less clear due to the lower total dose, there was a decrease in the dose delivered to the heart, potentially reducing the risk of cardiac toxicity in the long-term, especially during the irradiation of the left breast, and a reduction in dose to the contra lateral breast. CONCLUSION: Respiratory-gated radiotherapy appears to be essential to reduce the risk of acute and late toxicities, especially for lungs and heart, during irradiation of non-small cells lung cancer and breast cancers.

Patient's perception of care quality during radiotherapy sessions using respiratory gating techniques: validation of a specific questionnaire.

This prospective study was designed to validate a questionnaire on patients' perception of care quality during respiratory-gated radiotherapy for breast or lung cancer. Psychometric tests were performed on selected patients. Confirmatory factorial analyses and capacity to discriminate the responses were achieved to validate the best model on 297 patients. Factorial analyses identified the following three scales: (a) perception of quality, (b) global satisfaction, and (c) physical or emotional experience. The scales were able to differentiate patients' responses according to radiotherapy modalities. The questionnaire presented adequate psychometric properties. This tool could be used for the assessment from the patient's point of view.

Structural adaptations of the heart to physical exercises in the metabolic syndrome

The objective of this investigation was to conduct a literature review on the structural adaptations of the heart to physical exercises in the Metabolic Syndrome. The search was conducted in the following electronic databases: PubMed, Web of Sciences, LILLACS and MEDLINE using keywords in English without time restrictions. The metabolic syndrome (MS) is characterized by a group of metabolic risk factors in a person. In Brazil, more than 300.000 people die every year of cardiovascular diseases. According to the Brazilian Ministry of Health, there are currently over 20 million hypertensive and 15 million have diabetes in the country, and this rate is increasing. Physical inactivity, in most individuals, leads to well characterized structural and functional cardiovascular alterations such as myocyte loss with subsequent hypertrophy of the remaining cells and reduction of the arterial complacency. However, the etiology of the cardiovascular alterations is still under investigation. The most likely mechanisms are related to the cumulative harm and several different aggressive factors. Oxidative stress, inflammations, and changes in cardiovascular gene expression seem to influence this system. The benefits of physical exercises have been studied combined with pharmacotherapy offering the opportunity of intervention in the process by using exercises and drugs that can reduce arterial rigidity, cardiac fibrosis, and ventricular hypertrophy.

Isotopic study of post-anthesis foliar incorporation of sulphur and nitrogen in wheat.

Nitrogen (N) and sulphur (S) supplies have a strong influence on the quality and quantity of wheat storage proteins, which play an important role in the bread-making process. In order to relate the incorporation and distribution of foliar N and S fertilisers at the post-anthesis stage to the quality of wheat, 15N and 34S isotopes were used as tracers. The incorporation of these tracers in different plant parts (leaves, stems, ears) and in each storage protein fraction (gliadins, HMW and LMW glutenin subunits) was determined by isotopic ratio mass spectrometry coupled with an elemental analyser (EA-IRMS). By this means, the true recovery coefficient of N and S (TRCNfertiliser and TRCSfertiliser) and the N and S derived from fertilisers (Ndff and Sdff) could be determined. The TRCNfertiliser and TRCSfertiliser values of the different plant parts provide evidence of the applied N and S assimilation and translocation from wheat leaves to the seeds. The determination of Ndff and Sdff incorporated into storage proteins shows the efficiency and the influence of N and S incorporation into each storage protein fraction. Moreover, a favourable stage for fertiliser application can be determined by the TRCNfertiliser values in the grain and in the whole plant. The fertilisers enriched in stable isotope used in the culture techniques can be a means of understanding the effectiveness of fertilisers in the expression of wheat quality.

Results of a control programme for the porcine reproductive and respiratory syndrome in the French 'Pays de la Loire' region.

The porcine reproductive and respiratory syndrome (PRRS) virus first entered the Pays de la Loire region in November 1992, with variable effects ranging from sub-clinical seroconversion to severe reproductive failure and piglet mortality, and significant reduction of daily weight gains in finishing pigs. An epidemiological survey was carried out in February 1993. Since the infection prevalence was low (11 infected out of 2310 herds), the pig population was of medium density and the eradication programme of Aujeszky's disease had been successful in the Pays de la Loire region, it was decided (in March 1993) to undertake a control programme for PRRS. In 1993, introduction of infected pigs was known to be the most frequent source by which PRRS virus entered a herd. In the absence of vaccination, this source of virus introduction was reduced by a control programme applied to all members of the regional pig industry, through the impetus of the leaders of the Regional Sanitary Defence Confederation (FRGDS). The control programme was applied on purchased animals (sows, boars, piglets), artificial insemination centres and other environmental factors (people, vehicles, materials, slurry,...). Moreover, pigs from many infected herds were slaughtered. Results showed that in a context of low prevalence and limited spreading to nearby herds, efficient control of animal movements limited the infection spread. At the end of 1993, the PRRS prevalence was 2.7% in the region. Two years after the first outbreak, the PRRS infection could be considered as controlled since 98% of the herds remained free. In order to maintain this low infected status, the control programme was renewed. From this study epidemiological investigations have raised two major initial sources of infection, the use of contaminated semen and the introduction of infected pigs. Around an infected herd, serological screening is still running to detect infection in nearby herds.