Leishmania Parasites Drive PD-L1 Expression in Mice and Human Neutrophils With Suppressor Capacity

Neutrophils play an important role in the outcome of leishmaniasis, contributing either to exacerbating or controlling the progression of infection, a dual effect whose underlying mechanisms are not clear. We recently reported that CD4+ and CD8+ T cells, and dendritic cells of Leishmania amazonensis-infected mice present high expression of PD-1 and PD-L1, respectively. Given that the PD-1/PD-L1 interaction may promote cellular dysfunction, and that neutrophils could interact with T cells during infection, we investigated here the levels of PD-L1 in neutrophils exposed to Leishmania parasites. We found that both, promastigotes and amastigotes of L. amazonensis induced the expression of PD-L1 in the human and murine neutrophils that internalized these parasites in vitro. PD-L1-expressing neutrophils were also observed in the ear lesions and the draining lymph nodes of L. amazonensis-infected mice, assessed through cell cytometry and intravital microscopy. Moreover, expression of PD-L1 progressively increased in neutrophils from ear lesions as the disease evolved to the chronic phase. Co-culture of infected neutrophils with in vitro activated CD8+ T cells inhibits IFN-γ production by a mechanism dependent on PD-1 and PD-L1. Importantly, we demonstrated that in vitro infection of human neutrophils by L braziliensis induced PD-L1+ expression and also PD-L1+ neutrophils were detected in the lesions of patients with cutaneous leishmaniasis. Taken together, these findings suggest that the Leishmania parasite increases the expression of PD-L1 in neutrophils with suppressor capacity, which could favor the parasite survival through impairing the immune response

Framingham coronary heart disease risk score can be predicted from structural brain images in elderly subjects

Recent literature has presented evidence that cardiovascular risk factors (CVRF) play an important role on cognitive performance in elderly individuals, both those who are asymptomatic and those who suffer from symptoms of neurodegenerative disorders. Findings from studies applying neuroimaging methods have increasingly reinforced such notion. Studies addressing the impact of CVRF on brain anatomy changes have gained increasing importance, as recent papers have reported gray matter loss predominantly in regions traditionally affected in Alzheimer’s disease (AD) and vascular dementia in the presence of a high degree of cardiovascular risk. In the present paper, we explore the association between CVRF and brain changes using pattern recognition techniques applied to structural MRI and the Framingham score (a composite measure of cardiovascular risk largely used in epidemiological studies) in a sample of healthy elderly individuals. We aim to answer the following questions: is it possible to decode (i.e., to learn information regarding cardiovascular risk from structural brain images) enabling individual predictions? Among clinical measures comprising the Framingham score, are there particular risk factors that stand as more predictable from patterns of brain changes? Our main findings are threefold: (i) we verified that structural changes in spatially distributed patterns in the brain enable statistically significant prediction of Framingham scores. This result is still significant when controlling for the presence of the APOE 4 allele (an important genetic risk factor for both AD and cardiovascular disease). (ii) When considering each risk factor singly, we found different levels of correlation between real and predicted factors; however, single factors were not significantly predictable from brain images when considering APOE4 allele presence as covariate. (iii) We found important gender differences, and the possible causes of that finding are discussed

Characteristics of mentally ill offenders from 100 psychiatric court reports

<p>Abstract</p> <p>Background</p> <p>There is an increasing probability that the psychiatrist will, willingly or not, come into contact with mentally ill offenders in the course of their practice. There are increasing rates of violence, substance abuse and other psychiatric disorders that are of legal importance. Therefore, the aim of this work was to investigate the rates of different mental disorders in 100 court reports and to investigate the characteristics of mentally ill offenders.</p> <p>Methods</p> <p>All cases referred from different departments of the legal system to the forensic committee for assessment of legal accountability over 13-months duration were included. A specially designed form was prepared for data collection. Cases were classified into five groups: murder, robbery, financial offences, violent and simple offences and a group for other offences. Data were subjected to statistical analysis and comparisons between different groups of subjects were performed by analysis of variance (ANOVA).</p> <p>Results</p> <p>Men constituted 93% of cases. In all, 73% of offenders were younger than 40 years old. Schizophrenia cases made up 13% of the total, substance related cases constituted 56% and amphetamine cases alone made up 21%; 10% of cases were antisocial personality disorders, and 51% of cases were classified as having a low education level. Unemployment was found in 34% of cases. The final decision of the forensic committee was full responsibility in 46% of cases and partial responsibility in 11% of cases, with 33% considered non-responsible. A total of 58% of cases had had contact with psychiatric healthcare prior to the offence and in 9% of cases contact had been in the previous 12 weeks. A history of similar offences was found in 32% of cases. In all, 14% of the offences were murders, 8% were sexual crimes, and 31% were violent/simple crimes.</p> <p>Conclusions</p> <p>The ability of the legal system to detect cases was good, while the ability of the healthcare system to predict crimes and offences was weak, as 58% of cases had had previous contact with the healthcare system previously. Substance abuse, especially amphetamine abuse, played an important role.</p

Observation of the Baryonic Flavor-Changing Neutral Current Decay Lambda_b -> Lambda mu+ mu-

We report the first observation of the baryonic flavor-changing neutral current decay Lambda_b -> Lambda mu+ mu- with 24 signal events and a statistical significance of 5.8 Gaussian standard deviations. This measurement uses ppbar collisions data sample corresponding to 6.8fb-1 at sqrt{s}=1.96TeV collected by the CDF II detector at the Tevatron collider. The total and differential branching ratios for Lambda_b -> Lambda mu+ mu- are measured. We find B(Lambda_b -> Lambda mu+ mu-) = [1.73+-0.42(stat)+-0.55(syst)] x 10^{-6}. We also report the first measurement of the differential branching ratio of B_s -> phi mu+ mu- using 49 signal events. In addition, we report branching ratios for B+ -> K+ mu+ mu-, B0 -> K0 mu+ mu-, and B -> K*(892) mu+ mu- decays.Comment: 8 pages, 2 figures, 4 tables. Submitted to Phys. Rev. Let

The Use of Spinning-Disk Confocal Microscopy for the Intravital Analysis of Platelet Dynamics in Response to Systemic and Local Inflammation

Platelets are central players in inflammation and are an important component of the innate immune response. The ability to visualize platelets within the live host is essential to understanding their role in these processes. Past approaches have involved adoptive transfer of labelled platelets, non-specific dyes, or the use of fluorescent antibodies to tag platelets in vivo. Often, these techniques result in either the activation of the platelet, or blockade of specific platelet receptors. In this report, we describe two new methods for intravital visualization of platelet biology, intravenous administration of labelled anti-CD49b, which labels all platelets, and CD41-YFP transgenic mice, in which a percentage of platelets express YFP. Both approaches label endogenous platelets and allow for their visualization using spinning-disk confocal fluorescent microscopy. Following LPS-induced inflammation, we were able to measure a significant increase in both the number and size of platelet aggregates observed within the vasculature of a number of different tissues. Real-time observation of these platelet aggregates reveals them to be large, dynamic structures that are continually expanding and sloughing-off into circulation. Using these techniques, we describe for the first time, platelet recruitment to, and behaviour within numerous tissues of the mouse, both under control conditions and following LPS induced inflammation

Rapid Accumulation of Polymorphonuclear Neutrophils in the Corpus luteum during Prostaglandin F2α-Induced Luteolysis in the Cow

Prostaglandin F2α (PGF2α) induces luteolysis within a few days in cows, and immune cells increase in number in the regressing corpus luteum (CL), implying that luteolysis is an inflammatory-like immune response. We investigated the rapid change in polymorphonuclear neutrophil (PMN) numbers in response to PGF2α administration as the first cells recruited to inflammatory sites, together with mRNA of interleukin-8 (IL-8: neutrophil chemoattractant) and P-selectin (leukocyte adhesion molecule) in the bovine CL. CLs were collected by ovariectomy at various times after PGF2α injection. The number of PMNs was increased at 5 min after PGF2α administration, whereas IL-8 and P-selectin mRNA increased at 30 min and 2 h, respectively. PGF2α directly stimulated P-selectin protein expression at 5–30 min in luteal endothelial cells (LECs). Moreover, PGF2α enhanced PMN adhesion to LECs, and this enhancement by PGF2α was inhibited by anti-P-selectin antibody, suggesting that P-selectin expression by PGF2α is crucial in PMN migration. In conclusion, PGF2α rapidly induces the accumulation of PMNs into the bovine CL at 5 min and enhances PMN adhesion via P-selectin expression in LECs. It is suggested that luteolytic cascade by PGF2α may involve an acute inflammatory-like response due to rapidly infiltrated PMNs