Abstract Infections are a leading cause of death in patients with acute CNS injury such as stroke. Recent experimental evidence indicated that stroke leads to suppression of innate and adaptive ...peripheral immune responses which predisposes to infection. However, less is known on phenotypic and functional immune alterations in correlation with the occurrence of infectious complications in patients with acute stroke. Experimental procedures: In the recently completed randomized, double blind, placebo-controlled Preventive Antibacterial Therapy in Stroke (PANTHERIS) trial on the efficacy of short-term antibacterial therapy to prevent the development of post-stroke infections, we assessed longitudinal changes in lymphocyte subpopulations and mitogen-induced lymphocytic interferon gamma (IFN)-γ production using flow cytometry in 80 patients with acute severe stroke at days 1, 3, 8, 90 and 180 after clinical onset. Plasma interleukin (IL)-6 and IL-10 concentration as well as urinary levels of norepinephrine and cortisol was assessed within the first 8 days after stroke. Patients of the placebo and verum (moxifloxacin) treatment groups who did or did not develop infections within 11 days after stroke were compared to identify immunological changes associated with the occurrence of post-stroke infections. Results: Rapid T-lymphopenia and long-lasting suppression of lymphocytic IFN-γ production were observed in all stroke patients. Patients of the placebo group who developed infections showed a trend toward greater decline of CD4+ Th cell counts and higher urinary levels of norepinephrine early after stroke than patients without infections. Onset of infections was accompanied with higher plasma IL-6 levels in the placebo group but not in the moxifloxacin group. In addition, an early rise in plasma IL-10 was detected in patients who developed infections despite preventive antibacterial treatment. Conclusion: A rapid loss and functional deactivation of T cells are common changes in stroke patients consistent with immunodepression after brain ischemia. A stronger decrease in cellular immune responses and an increased sympathetic activity after stroke are associated with a higher risk of infections. Increased plasma levels of the anti-inflammatory cytokine IL-10 early after stroke may identify patients who will not respond to preventive antibacterial therapy with moxifloxacin.
Infections are a leading cause of morbidity and mortality in patients with acute CNS injury. It has recently become clear that CNS injury significantly increases susceptibility to infection by ...brain-specific mechanisms: CNS injury induces a disturbance of the normally well balanced interplay between the immune system and the CNS. As a result, CNS injury leads to secondary immunodeficiency - CNS injury-induced immunodepression (CIDS) - and infection. CIDS might serve as a model for the study of the mechanisms and mediators of brain control over immunity. More importantly, understanding CIDS will allow us to work on developing effective therapeutic strategies, with which the outcome after CNS damage by a host of diseases could be improved by eliminating a major determinant of poor recovery.
Almost 40% of stroke patients have a poor outcome at 3 months after the index event. Predictors for stroke outcome in the early acute phase may help to tailor stroke treatment. Infection and ...inflammation are considered to influence stroke outcome.
In a prospective multicenter study in Germany and Spain, including 486 patients with acute ischemic stroke, we used multivariable regression analysis to investigate the association of poor outcome with monocytic HLA-DR (mHLA-DR) expression, interleukin 6 (IL-6), interleukin 10 (IL-10), tumor necrosis factor alpha (TNF-alpha) and lipopolysaccharide-binding protein (LBP) as markers for immunodepression, inflammation and infection. Outcome was assessed at 3 months after stroke via a structured telephone interview using the modified Rankin Scale (mRS). Poor outcome was defined as a mRS score of 3 or higher which included death. Furthermore, a time-to-event analysis for death within 3 months was performed.
Three-month outcome data was available for 391 patients. Female sex, older age, diabetes mellitus, atrial fibrillation, stroke-associated pneumonia (SAP) and higher National Institute of Health Stroke Scale (NIHSS) score as well as lower mHLA-DR levels, higher IL-6 and LBP-levels at day 1 were associated with poor outcome at 3 months in bivariate analysis. Furthermore, multivariable analysis revealed that lower mHLA-DR expression was associated with poor outcome. Female sex, older age, atrial fibrillation, SAP, higher NIHSS score, lower mHLA-DR expression and higher IL-6 levels were associated with shorter survival time in bivariate analysis. In multivariable analysis, SAP and higher IL-6 levels on day 1 were associated with shorter survival time.
SAP, lower mHLA-DR-expression and higher IL-6 levels on day one are associated with poor outcome and shorter survival time at 3 months after stroke onset.
www.clinicaltrials.gov, NCT01079728 , March 3, 2010.
Objectives
Stroke‐associated pneumonia (SAP) is a common complication with a known negative impact on neurological outcome. We developed a score to identify patients at highest risk of SAP in order ...to promote prophylactic measures.
Materials and Methods
We conducted a cohort study on a neurological intensive care unit in patients suffering from acute ischemic MCA infarction. Association of predefined demographics, comorbidities, and clinical characteristics with SAP was investigated using logistic regression analysis.
Results
Between 2003 and 2010, a total of 335 patients were included in this analysis. Frequency of SAP was 31.3%. A 12‐point scoring system was developed based on the following factors: Glasgow Coma Scale (GCS) GCS < 9 = 5, GCS 9–12 = 2, GCS > 12 = 0, age <60 = 0, 60–80 = 1, >80 = 2, increase in systolic arterial blood pressure >200 mmHg within the first 24 h after admission no = 0, yes = 2, and white blood cell count >11.000/μl no = 0, yes = 3. The score revealed excellent discrimination (AUC = 0.85) and calibration (Nagelkerke's R² = 0.46) properties. Predictive properties were reproduced in an internal validation group.
Conclusions
The PANTHERIS score is a simple scoring system for the prediction of SAP based on easy‐to‐assess parameters. By identifying patients at high risk, it may guide intense monitoring or prophylactic measures. This score needs to be validated within external datasets.
Chronic inflammatory demyelinating polyneuropathy (CIDP) is presented by a large heterogeneity of clinical phenotypes. Around 50% of patients suffer from typical CIDP and show better therapy response ...than atypical variants. The goal of our study was to search for cellular immunological differences in typical versus atypical CIDP in comparison to controls.
We evaluated 26 (9 typical, 17 atypical) patients with mainly active-unstable CIDP using clinical and immunological examinations (enzyme-linked immunospot assay ELISPOT, fluorescence-activated cell sorting FACS) in comparison to 28 healthy, age-matched controls (HC). Typical or atypical CIDP measurements were compared with HC using Kruskal-Wallis test.
Atypical CIDP patients showed increased frequencies of T cell subsets, especially CD4+ effector memory T cells (TEM) and CD4+ central memory T cells (TCM) as well as a tendency of higher T cell responses against the peripheral myelin antigens of PMP-22, P2, P0 and MBP peptides compared to typical CIDP. Searching for novel auto-antigens, we found that T cell responses against P0 180-199 as well as MBP 82-100 were significantly elevated in atypical CIDP patients vs. HC.
Our results indicate differences in underlying T cell responses between atypical and typical CIDP characterized by a higher peripheral myelin antigen-specific T cell responses as well as a specific altered CD4+ memory compartment in atypical CIDP. Larger multi-center studies study are warranted in order to characterize T cell auto-reactivity in atypical CIDP subgroups in order to establish immunological markers as a diagnostic tool.
Abstract
Gibberellin (GA) negatively affects color evolution and other ripening-related processes in non-climacteric fruits. The bioactive GA, gibberellic acid (GA
3
), is commonly applied at the ...light green-to-straw yellow transition to increase firmness and delay ripening in sweet cherry (
Prunus avium
L.), though causing different effects depending on the variety. Recently, we reported that GA
3
delayed the IAD parameter (a ripening index) in a mid-season variety, whereas GA
3
did not delay IAD but reduced it at ripeness in an early-season variety. To further explore this contrasting behavior between varieties, we analyzed the transcriptomic responses to GA
3
applied on two sweet cherry varieties with different maturity time phenotypes. At harvest, GA
3
produced fruits with less color in both varieties. Similar to our previous report, GA
3
delayed fruit color initiation and IAD only in the mid-season variety and reduced IAD at harvest only in the early-season variety. RNA-seq analysis of control- and GA
3
-treated fruits revealed that ripening-related categories were overrepresented in the early-season variety, including ‘photosynthesis’ and ‘auxin response’. GA
3
also changed the expression of carotenoid and abscisic acid (ABA) biosynthetic genes in this variety. In contrast, overrepresented categories in the mid-season variety were mainly related to metabolic processes. In this variety, some
PP2Cs
putative genes were positively regulated by GA
3
, which are negative regulators of ABA responses, and
MYB44-
like genes (putative repressors of
PP2Cs
expression) were downregulated. These results show that GA
3
differentially modulates the transcriptome at the onset of ripening in a variety-dependent manner and suggest that GA
3
impairs ripening through the modification of ripening associated gene expression only in the early-season variety; whereas in the mid-season variety, control of the ripening timing may occur through the
PP2C
gene expression regulation. This work contributes to the understanding of the role of GA in non-climacteric fruit ripening.
Peach fruit undergoes a rapid softening process that involves a number of metabolic changes. Storing fruit at low temperatures has been widely used to extend its postharvest life. However, this leads ...to undesired changes, such as mealiness and browning, which affect the quality of the fruit. In this study, a 2-D DIGE approach was designed to screen for differentially accumulated proteins in peach fruit during normal softening as well as under conditions that led to fruit chilling injury.
The analysis allowed us to identify 43 spots -representing about 18% of the total number analyzed- that show statistically significant changes. Thirty-nine of the proteins could be identified by mass spectrometry. Some of the proteins that changed during postharvest had been related to peach fruit ripening and cold stress in the past. However, we identified other proteins that had not been linked to these processes. A graphical display of the relationship between the differentially accumulated proteins was obtained using pairwise average-linkage cluster analysis and principal component analysis. Proteins such as endopolygalacturonase, catalase, NADP-dependent isocitrate dehydrogenase, pectin methylesterase and dehydrins were found to be very important for distinguishing between healthy and chill injured fruit. A categorization of the differentially accumulated proteins was performed using Gene Ontology annotation. The results showed that the 'response to stress', 'cellular homeostasis', 'metabolism of carbohydrates' and 'amino acid metabolism' biological processes were affected the most during the postharvest.
Using a comparative proteomic approach with 2-D DIGE allowed us to identify proteins that showed stage-specific changes in their accumulation pattern. Several proteins that are related to response to stress, cellular homeostasis, cellular component organization and carbohydrate metabolism were detected as being differentially accumulated. Finally, a significant proportion of the proteins identified had not been associated with softening, cold storage or chilling injury-altered fruit before; thus, comparative proteomics has proven to be a valuable tool for understanding fruit softening and postharvest.
Despite the agronomical importance and high synteny with other Prunus species, breeding improvements for cherry have been slow compared to other temperate fruits, such as apple or peach. However, the ...recent release of the peach genome v1.0 by the International Peach Genome Initiative and the sequencing of cherry accessions to identify Single Nucleotide Polymorphisms (SNPs) provide an excellent basis for the advancement of cherry genetic and genomic studies. The availability of dense genetic linkage maps in phenotyped segregating progenies would be a valuable tool for breeders and geneticists. Using two sweet cherry (Prunus avium L.) intra-specific progenies derived from crosses between 'Black Tartarian' × 'Kordia' (BT×K) and 'Regina' × 'Lapins'(R×L), high-density genetic maps of the four parental lines and the two segregating populations were constructed. For BT×K and R×L, 89 and 121 F(1) plants were used for linkage mapping, respectively. A total of 5,696 SNP markers were tested in each progeny. As a result of these analyses, 723 and 687 markers were mapped into eight linkage groups (LGs) in BT×K and R×L, respectively. The resulting maps spanned 752.9 and 639.9 cM with an average distance of 1.1 and 0.9 cM between adjacent markers in BT×K and R×L, respectively. The maps displayed high synteny and co-linearity between each other, with the Prunus bin map, and with the peach genome v1.0 for all eight LGs (LG1-LG8). These maps provide a useful tool for investigating traits of interest in sweet cherry and represent a qualitative advance in the understanding of the cherry genome and its synteny with other members of the Rosaceae family.
Scaling up additive manufacturing (AM) for automated building construction requires expertise from different fields of knowledge, including architecture, material science, engineering, and ...manufacturing to develop processes that work for practical applications. While concrete is a viable candidate for printing due to its common use in building, it raises important challenges in deposition due to the material deformation that occurs as concrete transitions from fresh to hardened states. This study aims to experimentally quantify the deformation of printed concrete layers under the influence of different processing variables, including layer thickness, printing orientation, and direction. A mixer-pump extrudes the material and an industrial 6-axis robotic arm, which provides various ranges of movement in different axes, layers the material. The results of this study can be used to develop a tool for predicting and accounting for the deformation of concrete layers during the AM process.
The domestication process of the common bean gave rise to six different races which come from the two ancestral genetic pools, the Mesoamerican (Durango, Jalisco, and Mesoamerica races) and the ...Andean (New Granada, Peru, and Chile races). In this study, a collection of 281 common bean landraces from Chile was analyzed using a 12K-SNP microarray. Additionally, 401 accessions representing the rest of the five common bean races were analyzed. A total of 2543 SNPs allowed us to differentiate a genetic group of 165 accessions that corresponds to the race Chile, 90 of which were classified as pure accessions, such as the bean types 'Tórtola', 'Sapito', 'Coscorrón', and 'Frutilla'. Our genetic analysis indicates that the race Chile has a close relationship with accessions from Argentina, suggesting that nomadic ancestral peoples introduced the bean seed to Chile. Previous archaeological and genetic studies support this hypothesis. Additionally, the low genetic diversity (π = 0.053; uHe = 0.53) and the negative value of Tajima' D (D = -1.371) indicate that the race Chile suffered a bottleneck and a selective sweep after its introduction, supporting the hypothesis that a small group of Argentine bean genotypes led to the race Chile. A total of 235 genes were identified within haplotype blocks detected exclusively in the race Chile, most of them involved in signal transduction, supporting the hypothesis that intracellular signaling pathways play a fundamental role in the adaptation of organisms to changes in the environment. To date, our findings are the most complete investigation associated with the origin of the race Chile of common bean.
PDF
