Central nervous system involvement by malignant cells is a rare complication of Waldenström macroglobulinemia, and this clinicopathological entity is referred to as the Bing-Neel syndrome. There is ...currently no consensus on the diagnostic criteria, therapeutic approaches and response evaluation for this syndrome. In this series, we retrospectively analyzed 44 French patients with Bing-Neel syndrome. Bing-Neel syndrome was the first manifestation of Waldenström macroglobulinemia in 36% of patients. When Waldenström macroglobulinemia was diagnosed prior to Bing-Neel syndrome, the median time interval between this diagnosis and the onset of Bing-Neel syndrome was 8.9 years. This study highlights the possibility of the occurrence of Bing-Neel syndrome without any other evidence of progression of Waldenström macroglobulinemia. The clinical presentation was heterogeneous without any specific signs or symptoms. Biologically, the median lymphocyte count in the cerebrospinal fluid was 31/mm(3). Magnetic resonance imaging revealed abnormalities in 78% of the cases. The overall response rate after first-line treatment was 70%, and the overall survival rate after the diagnosis of Bing-Neel syndrome was 71% at 5 years. Altogether, these results suggest that Bing-Neel syndrome should be considered in the context of any unexplained neurological symptoms associated with Waldenström macroglobulinemia. The diagnostic approach should be based on cerebrospinal fluid analysis and magnetic resonance imaging of the brain and spinal axis. It still remains difficult to establish treatment recommendations or prognostic factors in the absence of large-scale, prospective, observational studies.
We investigate in a 2D setting the scattering of time-harmonic electromagnetic waves by a plasmonic device, represented as a non-dissipative bounded and penetrable obstacle with a negative ...permittivity. Using the T-coercivity approach, we first prove that the problem is well-posed in the classical framework Hloc1 if the negative permittivity does not lie in some critical interval whose definition depends on the shape of the device. When the latter has corners, for values inside the critical interval, unusual strong singularities for the electromagnetic field can appear. In that case, well-posedness is obtained by imposing a radiation condition at the corners to select the outgoing black-hole plasmonic wave, that is the one which carries energy towards the corners. A simple and systematic criterion is given to define what is the outgoing solution. Finally, we propose an original numerical method based on the use of Perfectly Matched Layers at the corners. We emphasize that it is necessary to design an ad hoc technique because the field is too singular to be captured with standard finite element methods.
Abstract
Together with environmental factors, physiological maturity at birth is a major determinant for neonatal survival and postnatal development in mammalian species. Maturity at birth is the ...outcome of complex mechanisms of intra-uterine development and maturation during the end of gestation. In pig production, piglet preweaning mortality averages 20% of the litter and thus, maturity is a major welfare and economic concern. Here, we used both targeted and untargeted metabolomic approaches to provide a deeper understanding of the maturity in a model of lines of pigs divergently selected on residual feed intake (RFI), previously shown to have contrasted signs of maturity at birth. Analyses were conducted on plasma metabolome of piglets at birth and integrated with other phenotypic characteristics associated to maturity. We confirmed proline and myo-inositol, previously described for their association with delayed growth, as potential markers of maturity. Urea cycle and energy metabolism were found more regulated in piglets from high and low RFI lines, respectively, suggesting a better thermoregulation ability for the low RFI (with higher feed efficiency) piglets.
Protease Inhibitors (PI e.g., ritonavir (RTV) and lopinavir (LPV)) used to treat pregnant mothers infected by HIV induce prematurity and endocrine dysfunctions. The maintenance of pregnancy relies on ...placental hormone production (human Chorionic Gonadotrophin (hCG) and progesterone (P4)). Those functions are ensured by the villous trophoblast and are mainly regulated by the Unfolded Protein Response (UPR) pathway and mitochondria. We investigated, in vitro, if PI impair hCG and P4 production and the potential intracellular mechanisms involved. Term villous cytotrophoblast (VCT) were cultured with or without RTV or LPV from 6 to 48 h. VCT differentiation into syncytiotrophoblast (ST) was followed measuring hCG and P4 secretion. We evaluated the expression of P4 synthesis partners (Metastatic Lymph Node 64 (MLN64), cholesterol side-chain cleavage (P450SCC), Hydroxy-delta-5-Steroid Dehydrogenase and 3 Beta-and steroid delta-isomerase 1 (HSD3B1)), of mitochondrial pro-fusion factors (Mitofusin 2 (Mfn2), Optic Atrophy 1 (OPA1)) and of UPR factors (Glucose-Regulated Protein 78 (GRP78), Activating Transcription Factor 4 (ATF4), Activating Transcription Factor 6 (ATF6), spliced X-box Binding Protein 1 (sXBP1)). RTV had no significant effect on hCG and P4 secretion, whereas lopinavir significantly decreased both secretions. LPV also decreased P450SCC and HSD3B1 expression, whereas it increased Mfn2, GRP78 and sXBP1 expression in ST. RTV has no effect on the endocrine placenta. LPV impairs both villous trophoblast differentiation and P4 production. It is likely to act via mitochondrial fusion and UPR pathway activation. These trophoblastic alterations may end in decreased P4 levels in maternal circulation, inducing prematurity.
Adaptation to the sensory environment is essential in everyday life, to anticipate future events and quickly detect and respond to changes; and to distinguish vocal variations in congeners, for ...communication. The aim of the current study was to explore the effects of the nature (vocal/non-vocal) of the information to be encoded, on the establishment of auditory regularities. In electrophysiology, neural adaptation is measured by the ‘Repetition Positivity’ (RP), which refers to an increase in positive potential, with the increasing number of repetitions of a same stimulus. The RP results from the combined variation of several ERP components; the P1, the first positivity (∼100 ms) may reflect the onset of repetition effects. We recorded auditory evoked potentials during a roving paradigm in which trains of 4, 8 or 16 repetitions of the same stimulus were presented. Sequences of vocal and non-vocal complex stimuli were delivered, to study the influence of the type of stimulation on the characteristics of the brain responses. The P1 to each train length, and the RP responses were recorded between 90 and 200 ms, reflecting adaptation for both vocal and non-vocal stimuli. RP was not different between vocal and non-vocal sequences (in latency, amplitude and spatial organization) and was found to be similar to that found in previous studies using pure tones, suggesting that the repetition suppression phenomena is somehow independent of the nature of the stimulus. However, results showed faster stabilization of the P1 amplitude for non-vocal stimuli than for vocal stimuli, which require more repetitions. This revealed different dynamics for the establishment of regularity encoding for non-vocal and vocal stimuli, indicating that the richness of vocal sounds may require further processing before full neural adaptation occurs.
Aims/hypothesis
This is an update of the results from the previous report of the CORONADO (Coronavirus SARS-CoV-2 and Diabetes Outcomes) study, which aims to describe the outcomes and prognostic ...factors in patients with diabetes hospitalised for coronavirus disease-2019 (COVID-19).
Methods
The CORONADO initiative is a French nationwide multicentre study of patients with diabetes hospitalised for COVID-19 with a 28-day follow-up. The patients were screened after hospital admission from 10 March to 10 April 2020. We mainly focused on hospital discharge and death within 28 days.
Results
We included 2796 participants: 63.7% men, mean age 69.7 ± 13.2 years, median BMI (25th–75th percentile) 28.4 (25.0–32.4) kg/m
2
. Microvascular and macrovascular diabetic complications were found in 44.2% and 38.6% of participants, respectively. Within 28 days, 1404 (50.2%; 95% CI 48.3%, 52.1%) were discharged from hospital with a median duration of hospital stay of 9 (5–14) days, while 577 participants died (20.6%; 95% CI 19.2%, 22.2%). In multivariable models, younger age, routine metformin therapy and longer symptom duration on admission were positively associated with discharge. History of microvascular complications, anticoagulant routine therapy, dyspnoea on admission, and higher aspartate aminotransferase, white cell count and C-reactive protein levels were associated with a reduced chance of discharge. Factors associated with death within 28 days mirrored those associated with discharge, and also included routine treatment by insulin and statin as deleterious factors.
Conclusions/interpretation
In patients with diabetes hospitalised for COVID-19, we established prognostic factors for hospital discharge and death that could help clinicians in this pandemic period.
Trial registration
Clinicaltrials.gov
identifier: NCT04324736
Graphical abstract
Mycobacterium tuberculosis strains of the Beijing lineage are globally distributed and are associated with the massive spread of multidrug-resistant (MDR) tuberculosis in Eurasia. Here we ...reconstructed the biogeographical structure and evolutionary history of this lineage by genetic analysis of 4,987 isolates from 99 countries and whole-genome sequencing of 110 representative isolates. We show that this lineage initially originated in the Far East, from where it radiated worldwide in several waves. We detected successive increases in population size for this pathogen over the last 200 years, practically coinciding with the Industrial Revolution, the First World War and HIV epidemics. Two MDR clones of this lineage started to spread throughout central Asia and Russia concomitantly with the collapse of the public health system in the former Soviet Union. Mutations identified in genes putatively under positive selection and associated with virulence might have favored the expansion of the most successful branches of the lineage.
Transmission problems with sign-changing coefficients occur in electromagnetic theory in the presence of negative materials surrounded by classical materials. For general geometries, establishing ...Fredholmness of these transmission problems is well-understood thanks to the
T
-coercivity approach. Moreover, for a plane interface, there exist meshing rules that guarantee an optimal convergence rate for the finite element approximation. We propose here a new treatment at the corners of the interface which allows to design meshing rules for an arbitrary polygonal interface and then recover standard error estimates. This treatment relies on the use of simple geometrical transforms to define the meshes. Numerical results illustrate the importance of this new design.
Besides neuraxial analgesia, nonpharmacological methods are also proposed to help women coping with pain during labor. We aimed to identify the individual and organizational factors associated with ...the use of nonpharmacological analgesia for labor pain management. Women who attempted vaginal delivery with labor analgesia were selected among participants included in the 2016 National Perinatal Survey, a population-based cross-sectional study. Labor analgesia was studied as neuraxial analgesia alone, nonpharmacological analgesia alone, and neuraxial and nonpharmacological analgesia combined. The associations were studied using multilevel multinomial logistic regression. Among the 9231 women included, 62.4% had neuraxial analgesia alone, 6.4% had nonpharmacological analgesia alone, and 31.2% had both. Nonpharmacological analgesia alone or combined with neuraxial analgesia were both associated with high educational level (adjusted odds ratio 1.55; 95% confidence interval CI, 1.08-2.23 and 1.39; 95% CI, 1.18-1.63), antenatal preference to deliver without neuraxial analgesia, and public maternity unit status. Nonpharmacological analgesia alone was more frequent among multiparous women, and in maternity units with an anesthesiologist not dedicated to delivery unit (1.57; 95% CI, 1.16-2.12) and with the lowest midwife workload (2.15; 95% CI, 1.43-3.22). Neuraxial and nonpharmacological analgesia combined was negatively associated with inadequate prenatal care (0.70; 95% CI, 0.53-0.94). In France, most women who had nonpharmacological analgesia during labor used it as a complementary method to neuraxial analgesia. The use of nonpharmacological analgesia combined with neuraxial analgesia mainly depends on the woman's preference, but also on socioeconomic factors, quality of prenatal care, and care organization.
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