General method for prediction of thermal conductivity for well-characterized hydrocarbon mixtures and fuels up to extreme conditions using entropy scaling

A general and efficient technique is developed to predict the thermal conductivity of well-characterized hydrocarbon mixtures, rocket propellant (RP) fuels, and jet fuels up to high temperatures and high pressures (HTHP). The technique is based upon entropy scaling using the group contribution method coupled with the Perturbed-Chain Statistical Associating Fluid Theory (PC-SAFT) equation of state. The mixture number averaged molecular weight and hydrogen to carbon ratio are used to define a single pseudo-component to represent the compounds in a well-characterized hydrocarbon mixture or fuel. With these two input parameters, thermal conductivity predictions are less accurate when the mixture contains significant amounts of iso-alkanes, but the predictions improve when a single thermal conductivity data point at a reference condition is used to fit one model parameter. For eleven binary mixtures and three ternary mixtures at conditions from 288 to 360 K and up to 4,500 bar, thermal conductivities are predicted with mean absolute percent deviations (MAPDs) of 16.0 and 3.0% using the two-parameter and three-parameter models, respectively. Thermal conductivities are predicted for three RP fuels and three jet fuels at conditions from 293 to 598 K and up to 700 bar with MAPDs of 14.3 and 2.0% using the two-parameter and three-parameter models, respectively

Inhibiting ERK Activation with CI-1040 Leads to Compensatory Upregulation of Alternate MAPKs and Plasminogen Activator Inhibitor-1 following Subtotal Nephrectomy with No Impact on Kidney Fibrosis

Extracellular-signal regulated kinase (ERK) activation by MEK plays a key role in many of the cellular processes that underlie progressive kidney fibrosis including cell proliferation, apoptosis and transforming growth factor β1-mediated epithelial to mesenchymal transition. We therefore assessed the therapeutic impact of ERK1/2 inhibition using a MEK inhibitor in the rat 5/6 subtotal nephrectomy (SNx) model of kidney fibrosis. There was a twentyfold upregulation in phospho-ERK1/2 expression in the kidney after SNx in Male Wistar rats. Rats undergoing SNx became hypertensive, proteinuric and developed progressive kidney failure with reduced creatinine clearance. Treatment with the MEK inhibitor, CI-1040 abolished phospho- ERK1/2 expression in kidney tissue and prevented phospho-ERK1/2 expression in peripheral lymphocytes during the entire course of therapy. CI-1040 had no impact on creatinine clearance, proteinuria, glomerular and tubular fibrosis, and α-smooth muscle actin expression. However, inhibition of ERK1/2 activation led to significant compensatory upregulation of the MAP kinases, p38 and JNK in kidney tissue. CI-1040 also increased the expression of plasminogen activator inhibitor-1 (PAI-1), a key inhibitor of plasmin-dependent matrix metalloproteinases. Thus inhibition of ERK1/2 activation has no therapeutic effect on kidney fibrosis in SNx possibly due to increased compensatory activation of the p38 and JNK signalling pathways with subsequent upregulation of PAI-1

Disruption of Conscious Access in Psychosis Is Associated with Altered Structural Brain Connectivity

According to global neuronal workspace (GNW) theory, conscious access relies on long-distance cerebral connectivity to allow a global neuronal ignition coding for conscious content. In patients with schizophrenia and bipolar disorder, both alterations in cerebral connectivity and an increased threshold for conscious perception have been reported. The implications of abnormal structural connectivity for disrupted conscious access and the relationship between these two deficits and psychopathology remain unclear. The aim of this study was to determine the extent to which structural connectivity is correlated with consciousness threshold, particularly in psychosis. We used a visual masking paradigm to measure consciousness threshold, and diffusion MRI tractography to assess structural connectivity in 97 humans of either sex with varying degrees of psychosis: healthy control subjects (n = 46), schizophrenia patients (n = 25), and bipolar disorder patients with (n = 17) and without (n = 9) a history of psychosis. Patients with psychosis (schizophrenia and bipolar disorder with psychotic features) had an elevated masking threshold compared with control subjects and bipolar disorder patients without psychotic features. Masking threshold correlated negatively with the mean general fractional anisotropy of white matter tracts exclusively within the GNW network (inferior frontal-occipital fasciculus, cingulum, and corpus callosum). Mediation analysis demonstrated that alterations in long-distance connectivity were associated with an increased masking threshold, which in turn was linked to psychotic symptoms. Our findings support the hypothesis that long-distance structural connectivity within the GNW plays a crucial role in conscious access, and that conscious access may mediate the association between impaired structural connectivity and psychosis

Clinical and Prognostic Value of Immunogenetic Characteristics in Anti-LGI1 Encephalitis

OBJECTIVE: Antibodies against leucine-rich glioma-inactivated 1 (LGI1-Abs) characterize a limbic encephalitis (LE) strongly associated with HLA-DRB1*07:01, although some patients lack LGI1-Abs in CSF or do not carry this allele. Whether they represent a different subtype of disease or have different prognoses is unclear. METHODS: Retrospective analysis of clinical features, IgG isotypes, and outcome according to LGI1-Ab CSF positivity and DRB1*07:01 in a cohort of anti-LGI1 LE patients. RESULTS: Patients with LGI1-Abs detected in both CSF and serum (105/134, 78%) were compared with those who were CSF negative (29/134, 22%). Both groups had similar clinical features and serum levels, but CSF-positive patients had shorter diagnostic delay, more frequently hyponatremia, inflammatory CSF, and abnormal MRI (p 0.05). HLA and IgG isotypes were not associated with poor outcome (mRS >2 at last follow-up) in univariate analyses; CSF positivity was only identified as a poor outcome predictor in the multivariate analysis including the complete follow-up, whereas age and female sex also remained when just the first year was considered. CONCLUSIONS: LE without CSF LGI1-Abs is clinically indistinguishable and likely reflects just a lesser LGI1-Ab production. HLA association is sex and age biased and presents clinical particularities, suggesting subtle differences in the immune response. Long-term outcome depends mostly on demographic characteristics and the intensity of the intrathecal synthesis

Secretory IgA mediates retrotranscytosis of intact gliadin peptides via the transferrin receptor in celiac disease

Celiac disease (CD) is an enteropathy resulting from an abnormal immune response to gluten-derived peptides in genetically susceptible individuals. This immune response is initiated by intestinal transport of intact peptide 31-49 (p31-49) and 33-mer gliadin peptides through an unknown mechanism. We show that the transferrin receptor CD71 is responsible for apical to basal retrotranscytosis of gliadin peptides, a process during which p31-49 and 33-mer peptides are protected from degradation. In patients with active CD, CD71 is overexpressed in the intestinal epithelium and colocalizes with immunoglobulin (Ig) A. Intestinal transport of intact p31-49 and 33-mer peptides was blocked by polymeric and secretory IgA (SIgA) and by soluble CD71 receptors, pointing to a role of SIgA–gliadin complexes in this abnormal intestinal transport. This retrotranscytosis of SIgA–gliadin complexes may promote the entry of harmful gliadin peptides into the intestinal mucosa, thereby triggering an immune response and perpetuating intestinal inflammation. Our findings strongly implicate CD71 in the pathogenesis of CD

Suicidal attempt among patients with schizophrenia: A cross-sectional study from Morocco

Suicide constitutes the greatest risk factor for mortality in individuals with schizophrenia. Although numerous risk factors have been suggested as important predictors of suicidality in schizophrenia, most studies have focused on Caucasian and Chinese patients. This study aimed to examine the prevalence of suicide attempts in schizophrenia patients in Rabat-Sale-Kenitra, Morocco, and to identify associated clinical and sociodemographic characteristics. A cross-sectional study was conducted at the Ar-RAZI Psychiatric Center of Ibn Sina Hospital in Rabat. We examined 175 Moroccan schizophrenic patients. The sociodemographic and clinical variables were analyzed based on the presence or absence of suicide attempts. The prevalence of suicide attempts among patients was 32%. 43% of them had reported multiple suicide attempts. The majority of those who attempted suicide were single, younger, and with a lower economic status. Visual hallucinations were significantly prevalent among attempter patients compared to non-attempters (p =0.032). Consequently, visual hallucinations could be a risk factor for suicide attempts in the Moroccan population. Understanding sociodemographic and clinical characteristics associated with suicide attempts can help identify patients at higher risk and provide appropriate support and interventions to prevent suicide among the Moroccan population