Appropriate Duration of Antimicrobial Treatment for Prosthetic Joint Infections: A Narrative Review.

Prosthetic joint infections are considered difficult to treat they needing aggressive surgery and long antimicrobial treatments. However, the exact duration of these therapies has been established empirically. In the last years, several studies have explored the possibility of reducing the length of treatment in this setting, with conflicting results. In this narrative review, we critically appraise the published evidence, considering the different surgical approaches (implant retention [DAIR] and one-step and two-step exchange procedures) separately. In patients managed with DAIR, usually treated for at least 12 weeks, a large, randomized trial failed to show that 6 weeks were non-inferior. However, another randomized clinical trial supports the use of 8 weeks, as long as the surgical conditions are favorable and antibiotics with good antibiofilm activity can be administered. In patients managed with a two-step exchange procedure, usually treated during 6 weeks, a randomized clinical trial showed the efficacy of a 4-week course of antimicrobials. Also, the use of local antibiotics may allow the use of even shorter treatments. Finally, in the case of one-step exchange procedures, there is a trend towards reducing the length of therapy, and the largest randomized clinical trial supports the use of 6 weeks of therapy.

Jasmonates and Ethylene Shape Floridoside Synthesis during Carposporogenesis in the Red Seaweed Grateloupia imbricata.

Floridoside is a galactosyl-glycerol compound that acts to supply UDP-galactose and functions as an organic osmolyte in response to salinity in Rhodophyta. Significantly, the UDP-galactose pool is shared for sulfated cell wall galactan synthesis, and, in turn, affected by thallus development alongside carposporogenesis induced by volatile growth regulators, such as ethylene and methyl jasmonate, in the red seaweed Grateloupia imbricata. In this study, we monitored changes in the floridoside reservoir through gene expression controlling both the galactose pool and glyceride pool under different reproductive stages of G. imbricata and we considered changing salinity conditions. Floridoside synthesis was followed by expression analysis of galactose-1-phosphate uridyltransferase (GALT) as UDP-galactose is obtained from UDP-glucose and glucose-1P, and through α-galactosidase gene expression as degradation of floridoside occurs through the cleavage of galactosyl residues. Meanwhile, glycerol 3-phosphate is connected with the galactoglyceride biosynthetic pathway by glycerol 3-phosphate dehydrogenase (G3PD), monogalactosyl diacylglyceride synthase (MGDGS), and digalactosyl diacylglyceride synthase (DGDGS). The results of our study confirm that low GALT transcripts are correlated with thalli softness to locate reproductive structures, as well as constricting the synthesis of UDP-hexoses for galactan backbone synthesis in the presence of two volatile regulators and methionine. Meanwhile, α-galactosidase modulates expression according to cystocarp maturation, and we found high transcripts in late development stages, as occurred in the presence of methyljasmonate, compared to early stages in ethylene. Regarding the acylglyceride pool, the upregulation of G3PD, MGDGS, and DGDGS gene expression in G. imbricata treated with MEJA supports lipid remodeling, as high levels of transcripts for MGDGS and DGDGS provide membrane stability during late development stages of cystocarps. Similar behavior is assumed in three naturally collected thalli development stages-namely, fertile, fertilized, and fertile-under 65 psu salinity conditions. Low transcripts for α-galactosidase and high for G3PD are reported in infertile and fertilized thalli, which is the opposite to high transcripts for α-galactosidase and low for G3PD encountered in fertile thalli within visible cystocarps compared to each of their corresponding stages in 35 psu. No significant changes are reported for MGDGS and DGDGS. It is concluded that cystocarp and thallus development stages affect galactose and glycerides pools with interwoven effects on cell wall polysaccharides.

Cell Count Differentials by Cytomorphology and Next-Generation Flow Cytometry in Bone Marrow Aspirate: An Evidence-Based Approach.

Despite a lack of evidence, a bone marrow aspirate differential of 500 cells is commonly used in the clinical setting. We aimed to test the performance of 200-cell counts for daily hematological workup. In total, 660 consecutive samples were analyzed recording differentials at 200 and 500 cells. Additionally, immunophenotype results and preanalytical issues were also evaluated. Clinical and statistical differences between both cutoffs and both methods were checked. An independent control group of 122 patients was included. All comparisons between both cutoffs and both methods for all relevant types of cells did not show statistically significant differences. No significant diagnostic discrepancies were demonstrated in the contingency table analysis. This is a real-life study, and some limitations may be pointed out, such as a different sample sizes according to the type of cell in the immunophenotype analysis, the lack of standardization of some preanalytical events, and the relatively small sample size of the control group. The comparisons of differentials by morphology on 200 and 500 cells, as well as by morphology (both cutoffs) and by immunophenotype, are equivalent from the clinical and statistical point of view. The preanalytical issues play a critical role in the assessment of bone marrow aspirate samples.

Risk Factors and Outcomes for Multidrug Resistant Pseudomonas aeruginosa Infection in Immunocompromised Patients.

Background: Pseudomonas aeruginosa (PSA) infection often occurs in immunocompromised patients, which also face an increased risk of multidrug-resistant (MDR) bacteria. A deeper knowledge of the risk factors for MDR-PSA infection in this patient population may help to choose appropriate empirical antibiotic therapy. Methods: a single-center case-control (1:2) retrospective study that included 48 patients with underlying immunosuppression developing MDR-PSA infection (cases) and 96 patients also immunocompromised that were infected with non-MDR-PSA (controls) was conducted. Both groups were matched by site of infection, clinical features and type of immunosuppression. Risk factors for MDR-PSA were assessed by logistic regression. Clinical outcomes were also compared between both groups. Results: immunosuppression was due to solid cancer in 63 (43.8%) patients, solid organ transplantation in 39 (27.1%), hematological disease in 35 (24.3%) and other causes in 7 (4.9%). Independent risk factors for MDR-PSA infection were diabetes mellitus (odds ratio [OR]: 4.74; 95% confidence interval [CI]: 1.63−13.79; p = 0.004), antibiotic therapy in the previous 3 months (OR: 5.32; 95% CI: 1.93−14.73; p = 0.001), previous MDR-PSA colonization (OR: 42.1; 95% CI: 4.49−394.8; p = 0.001) and septic shock (OR: 3.73; 95% CI: 1.36−10.21; p = 0.010). MDR-PSA cases were less likely to receive adequate empirical therapy (14 [29.2%] vs. 69 [71.9%]; p < 0.001). 30-day clinical improvement was less common in MDR-PSA cases (25 [52.1%] vs. 76 [79.2%]; p = 0.001). Conclusions: diabetes mellitus, previous MDR-PSA colonization, prior receipt of antibiotics and septic shock acted as risk factors for developing MDR-PSA infections in immunocompromised patients, who have a poorer outcome than those infected with non-MDR-PSA strains.

S-Assimilation Influences in Carrageenan Biosynthesis Genes during Ethylene-Induced Carposporogenesis in Red Seaweed Grateloupia imbricata.

The synthesis of cell-wall sulfated galactans proceeds through UDP galactose, a major nucleotide sugar in red seaweed, whilst sulfate is transported through S-transporters into algae. Moreover, synthesis of ethylene, a volatile plant growth regulator that plays an important role in red seaweed reproduction, occurs through S-adenosyl methionine. This means that sulfur metabolism is involved in reproduction events as well as sulfated galactan synthesis of red seaweed. In this work we study the effects of methionine and MgSO4 on gene expression of polygalactan synthesis through phosphoglucomutase (PGM) and galactose 1 phosphate uridyltransferase (GALT) and of sulfate assimilation (S-transporter and sulfate adenylyltransferase, SAT) using treatment of ethylene for 15 min, which elicited cystocarp development in Grateloupia imbricata. Also, expressions of carbohydrate sulfotransferase and galactose-6-sulfurylase in charge of the addition and removal of sulfate groups to galactans backbone were examined. Outstanding results occurred in the presence of methionine, which provoked an increment in transcript number of genes encoding S-transporter and assimilation compared to controls regardless of the development stage of thalli. Otherwise, methionine diminished the transcript levels of PGM and GALT and expressions are associated with the fertilization stage of thalli of G. imbricata. As opposite, methionine and MgSO4 did not affect the transcript number of carbohydrate sulfotransferase and galactose-6-sulfurylase. Nonetheless, differential expression was obtained for sulfurylases according to the development stages of thalli of G. imbricata.

Validity of the classification of emergency service requests related to suicidal behavior / Validez de la clasificación de las demandas por conducta suicida a un servicio de emergencias

Abstract Introduction Suicide attempts are the most predictive risk factor for suicide deaths. Most people who attempt suicide receive care from out-of-hospital Emergency Services (OES), where these requests are managed and classified. Objective Validate the Emergency Coordination Center (ECC) classification for the detection of suicidal behavior requests. Method A descriptive, cross-sectional study of requests to the ECC of Málaga (Spain) during 2013 and 2014 was conducted. To classify the requests, the authors considered the ECC categorization when answering the call and the clinical assessment of the healthcare professional when attending the person who had made the call at the scene, which was considered the reference standard. To analyze the validity of the ECC classification system, sensitivity, specificity, and positive and negative predictive values (PPV and NPV) were calculated. Results The total number of requests for medical assistance analyzed was 112,599. The validity indicators of the classification system for suicidal behavior were sensitivity = 44.78%, specificity = 99.34%, PPV = 46.91% and NPV = 99.28%. Discussion and conclusion The ECC classification system has a lower capacity to detect the presence of suicidal behavior and a higher capacity to identify its absence in the requests received. OES provide key information on suicidal behavior requests as they can be one of the first places people with this problem go to. It would therefore be extremely useful to improve the classification systems for requests related to suicidal behavior.

Resumen Introducción Los intentos de suicidio constituyen el factor de riesgo más predictivo de todos los casos de suicidio consumado. La mayoría de las personas que intentan suicidarse reciben atención en los Servicios de Urgencias Extrahospitalarios (SUE) donde se gestionan y clasifican estas demandas. Objetivo Validar la clasificación del Centro Coordinador de Urgencias y Emergencias (CCUE) para detectar las demandas relacionadas con la conducta suicida. Método Se llevó a cabo un estudio descriptivo y transversal de las demandas al CCUE de Málaga (España) realizadas durante 2013 y 2014. Para su clasificación se tuvo en cuenta la categorización en el CCUE al responder la llamada y el juicio clínico del profesional sanitario cuando atiende al demandante in situ, considerando éste como patrón de referencia. Para evaluar la validez del sistema de clasificación se calcularon la sensibilidad, la especificidad y los valores predictivos positivo (VPP) y negativo (VPN). Resultados El total de demandas sanitarias analizadas fue de 112,599. Los indicadores de validez del sistema de clasificación para las demandas por conductas de suicidio fueron una sensibilidad = 44.78%, especificidad = 99.34%, VPP = 46.91% y VPN = 99.28%. Discusión y conclusión El sistema de clasificación del CCUE presenta una capacidad más baja para detectar presencia de conducta suicida comparada con una capacidad más alta para identificar su ausencia en las demandas recibidas. Los SUE aportan información relevante sobre las demandas por conducta suicida ya que pueden ser uno de los primeros lugares a los que acuden las personas con este problema. Por ello, sería de gran utilidad mejorar los sistemas de clasificación de las demandas por conducta suicida.

Derivation of a score to predict infection due to multidrug-resistant Pseudomonas aeruginosa: a tool for guiding empirical antibiotic treatment.

OBJECTIVES: Multidrug-resistant Pseudomonas aeruginosa (MDR-PSA) constitutes an emerging health problem. A predictive score of MDR-PSA infection would allow an early adaptation of empirical antibiotic therapy. METHODS: We performed a single-centre case-control (1:2) retrospective study including 100 patients with MDR-PSA and 200 with a non-MDR-PSA infection. Cases and controls were matched by site of infection, clinical characteristics and immunosuppression. A point risk score for prediction of MDR-PSA infection was derived from a logistic regression model. Secondary outcomes (clinical improvement, complications and discharge) were also compared. RESULTS: Cases with MDR-PSA infection were younger than controls (67.5 vs. 73.0 y; P = 0.031) and have more frequent cirrhosis (9% vs. 2%; P = 0.005). Independent risk factors for MDR-PSA infection were prior antibiotic treatment (80% vs. 50.5%; P < 0.001), prior colonisation with MDR bacteria (41% vs. 13.5%; P < 0.001), hospital-acquired infection (63% vs. 47%; P = 0.009) and septic shock at diagnosis (33% vs. 14%; P < 0.001). Adequate therapy was less frequent in MDR-PSA infections (31% vs. 66.5% for empirical therapy; P < 0.001). The risk score included: previous MDR-PSA isolation (11 points), prior antibiotic use (3 points), hospital-acquired infection (2 points) and septic shock at diagnosis (2 points). It showed an area under the curve of 0.755 (95% CI: 0.70-0.81) and allowed to classify individual risk into various categories: 0-2 points (<20%), 3-5 points (25%-45%), 7-11 points (55%-60%), 13-16 points (75%-87%) and a maximum of 18 points (93%). CONCLUSION: Infections due to MDR-PSA have a poorer prognosis than those produced by non-MDR-PSA. Our score could guide empirical therapy for MDR-PSA when P. aeruginosa is isolated.

Negative Clinical Evolution in COVID-19 Patients Is Frequently Accompanied With an Increased Proportion of Undifferentiated Th Cells and a Strong Underrepresentation of the Th1 Subset.

The severity of SARS-CoV-2 infection has been related to uncontrolled inflammatory innate responses and impaired adaptive immune responses mostly due to exhausted T lymphocytes and lymphopenia. In this work we have characterized the nature of the lymphopenia and demonstrate a set of factors that hinder the effective control of virus infection and the activation and arming of effector cytotoxic T CD8 cells and showing signatures defining a high-risk population. We performed immune profiling of the T helper (Th) CD4+ and T CD8+ cell compartments in peripheral blood of 144 COVID-19 patients using multiparametric flow cytometry analysis. On the one hand, there was a consistent lymphopenia with an overrepresentation of non-functional T cells, with an increased percentage of naive Th cells (CD45RA+, CXCR3-, CCR4-, CCR6-, CCR10-) and persistently low frequency of markers associated with Th1, Th17, and Th1/Th17 memory-effector T cells compared to healthy donors. On the other hand, the most profound alteration affected the Th1 subset, which may explain the poor T cells responses and the persistent blood virus load. Finally, the decrease in Th1 cells may also explain the low frequency of CD4+ and CD8+ T cells that express the HLA-DR and CD38 activation markers observed in numerous patients who showed minimal or no lymphocyte activation response. We also identified the percentage of HLA-DR+CD4+ T cells, PD-1+CD+4/CD8+ T cells in blood, and the neutrophil/lymphocyte ratio as useful factors for predicting critical illness and fatal outcome in patients with confirmed COVID-19.

Unexpected Toxicity of Green Tea Polyphenols in Combination with the Sambucus RIL Ebulin.

The safety of concentrated food complements intake is a major health concern. It has been well established that green tea polyphenols (GTPs) consumption promotes healthy effects. However, the ingestion of large amounts of GTPs is a matter of controversy due to reported adverse effects. We underwent a preliminary exploration of the effects of the oral administration of a standardized concentrated GTPs preparation on mice which suffered from reversible intestinal derangement promoted by sublethal amounts of the antiribosomal lectin ebulin f from dwarf elder (Sambucus ebulus L.). Neither independent oral administration of 30 mg/kg body weight Polyphenon 60 nor intraperitoneal administration of 2.5 mg/kg body weight ebulin f triggered lethal toxicity. In contrast, the simultaneous administration of these same doses of both Polyphenon 60 and ebulin f triggered an important and unexpected synergistic toxic action featured by the biphasic reduction of weight, which continued after eight days, reaching a reduction of 40%. Lethality appeared 2 days after the onset of the combined treatment and reached more than 50% after 10 days.

Expression of Genes Related to Carrageenan Synthesis during Carposporogenesis of the Red Seaweed Grateloupia imbricata.

Carrageenan, the foremost constituent of extracellular matrix of some rhodophyta, is a galactan backbone with a different number of sulphate groups attached. Variations of degree of sulphation are associated with different types of carrageenans, which vary according to seaweed life cycles, and have consequences for the exploitation of this raw material. In this work, we used three well-recognised stages of development thalli and two stages of cystocarp maturation to analyse genes that encode addition and elimination of sulphate groups to cell-wall galactan of the red seaweed Grateloupia imbricata. Expressions of carbohydrate sulfotransferase and galactose-6 sulfurylase and genes encoding stress proteins such as cytochrome P450 and WD40, were examined. Results showed that transcript expression of carbohydrate sulfotransferase occurs at all stage of thalli development. Meanwhile galactose-6 sulfurylase expressions displayed different roles, which could be related to a temporal regulation of cystocarp maturation. Cytochrome P450 and WD40 are related to the disclosure and maturation of cystocarps of G. imbricata. Our conclusion is that differential expression of genes encoding proteins involved in the sulphation and desulphation of galactan backbone is associated with alterations in thalli development and cystocarp maturation in the red seaweed Grateloupia imbricata. Exploitation of industry-valued carrageenan will depend on insight into gene mechanisms of red seaweeds.

Tumor genetic alterations and features of the immune microenvironment drive myelodysplastic syndrome escape and progression.

The transformation and progression of myelodysplastic syndromes (MDS) to secondary acute myeloid leukemia (sAML) involve genetic, epigenetic, and microenvironmental factors. Driver mutations have emerged as valuable markers for defining risk groups and as candidates for targeted treatment approaches in MDS. It is also evident that the risk of transformation to sAML is increased by evasion of adaptive immune surveillance. This study was designed to explore the immune microenvironment, immunogenic tumor-intrinsic mechanisms (HLA and PD-L1 expression), and tumor genetic features (somatic mutations and altered karyotypes) in MDS patients and to determine their influence on the progression of the disease. We detected major alterations of the immune microenvironment in MDS patients, with a reduced count of CD4+ T cells, a more frequent presence of markers related to T cell exhaustion, a more frequent presence of myeloid-derived suppressor cells (MDSCs), and changes in the functional phenotype of NK cells. HLA Class I (HLA-I) expression was normally expressed in CD34+ blasts and during myeloid differentiation. Only two out of thirty-six patients with homozygosity for HLA-C groups acquired complete copy-neutral loss of heterozygosity in the HLA region. PD-L1 expression on the leukemic clone was also increased in MDS patients. Finally, no interplay was observed between the anti-tumor immune microenvironment and mutational genomic features. In summary, extrinsic and intrinsic immunological factors might severely impair immune surveillance and contribute to clonal immune escape. Genomic alterations appear to make an independent contribution to the clonal evolution and progression of MDS.

Analysis of the Transcriptome of the Red Seaweed Grateloupia imbricata with Emphasis on Reproductive Potential.

Grateloupia imbricata is an intertidal marine seaweed and candidate model organism for both industry and academic research, owing to its ability to produce raw materials such as carrageenan. Here we report on the transcriptome of G. imbricata with the aim of providing new insights into the metabolic pathways and other functional pathways related to the reproduction of Grateloupia species. Next-generation sequencing was carried out with subsequent de novo assembly and annotation using state-of-the-art bioinformatic protocols. The results show the presence of transcripts required for the uptake of glycerol, which is a specific carbon source for in vitro culture of G. imbricata and nucleotide sequences that are involved in polyamine-based biosynthesis, polyamine degradation, and metabolism of jasmonates and ethylene. Polyamines, ethylene and methyl jasmonate are plant growth regulators that elicit the development and maturation of cystocarps and the release of spores from seaweeds. Our results will inform studies of the mechanisms that control polysaccharide accumulation, cystocarp formation and spore release. Moreover, our transcriptome information clarifies aspects of red seaweed carposporogenesis with potential benefits for enhancing reproduction.

Prognostic Factors of Death in 151 Adults With Hemophagocytic Syndrome: Etiopathogenically Driven Analysis.

OBJECTIVE: To characterize the etiologies and clinical features at diagnosis of patients with hemophagocytic lymphohistiocytosis (HLH) and correlate these baseline features with survival using an etiopathogenically guided multivariable model. PATIENTS AND METHODS: The Spanish Group of Autoimmune Diseases HLH Study Group, formed in 2013, is aimed at collecting adult patients with HLH diagnosed in internal medicine departments between January 3, 2013, and October 28, 2017. RESULTS: The cohort consisted of 151 patients (91 men; mean age, 51.4 years). After a mean follow-up of 17 months (range, 1-142 months), 80 patients died. Time-to-event analyses for death identified a worse survival curve for patients with neoplasia (P<.001), mixed microbiological infections (P=.02), and more than 1 infection (P=.01) and glucocorticoid monotherapy (P=.02). According to univariate analyses, platelets of less than 100,000/mm3 (hazard ratio [HR], 3.39; 95% CI, 1.37-8.40), leukopenia (HR, 1.81; 95% CI, 1.01-3.23), severe hyponatremia (HR, 1.61; 95% CI, 1.02-2.54), disseminated intravascular coagulation (HR, 1.87; 95% CI, 1.05-3.34), bacterial infection (HR, 1.99; 95% CI, 1.09-3.63), mixed microbiological infections (HR, 3.42; 95% CI, 1.38-8.46), and 2 or more infectious triggers (HR, 2.95; 95% CI, 1.43-6.08) were significantly associated with death. In contrast, peripheral adenopathies (HR, 0.63; 95% CI, 0.40-0.98) and the immunosuppressive drug/intravenous immunoglobulin/biological therapies (HR, 0.44; 95% CI, 0.20-0.96) were protective against all-cause mortality. Multivariable Cox proportional hazards regression analysis identified 2 or more infectious triggers (HR, 3.14; 95% CI, 1.28-7.68) as the only variable independently associated with death. CONCLUSION: The mortality rate of adult patients diagnosed with HLH exceeds 50%. Infection with more than 1 microbiological agent was the only independent variable associated with mortality irrespective of the underlying disease, epidemiological profile, clinical presentation, and therapeutic management.

Analysis of ethylene-induced gene regulation during carposporogenesis in the red seaweed Grateloupia imbricata (Rhodophyta).

Ethylene favors carposporogenesis in the red seaweed Grateloupia imbricata. Analyses of cystocarp development in vitro in thalli treated with ethylene suggest an interconnection between polyamine and ethylene biosynthesis pathways. Yet, little is known about molecular mechanisms underlying carposporogenesis. Here, we used droplet digital PCR to analyze genes encoding enzymes related to polyamine (Spermidine [Spd] synthase) and ethylene (ACC synthase) synthesis; a pivotal compound of both pathways (S-adenosyl methionine synthase, SAMS); the gene that encodes amine oxidase, which is involved in polyamine degradation, and a candidate gene involved in seaweed reproduction (ornithine decarboxylase, ODC). In addition, we analyzed genes encoding proteins related to stress and reactive oxygen species, ascorbate peroxidase (APX), cytochrome P450 and WD 40. We characterized gene expression in fertilized and fertile thalli from G. imbricata that were exposed to ethylene for 15 min at two time points after treatment (1 and 7 d). The differential gene expression of SAMS, Spd synthase, ACC synthase, and cytochrome P450 was related to disclosure and development of cystocarps in fertilized thalli that transitioned from having no visible cystocarps at 1 d to developing cystocarps at 7 d. Likewise, cytochrome P450 was associated with cystocarp disclosure and maturation. In addition, amine oxidase and APX were involved in fine-tuning polyamine and reactive oxygen species during carposporogenesis, respectively, whereas WD 40 did so in relation to ethylene signaling. Expression of the candidate gene ODC was increased when cystocarps were not visible (fertilized thalli, 1d), as previously described. This analysis suggests developmental stage-specific roles for these genes during carposporogenesis.

TH1 and TH2 Cytokine Profiles as Predictors of Severity in Acute Pancreatitis.

OBJECTIVES: Acute pancreatitis (AP) is severe in up to 20% of patients, with a high mortality rate. Quantification of serum TH1 and TH2 cytokines may provide objective evidence to assess the severity of AP and predict its course. METHODS: One hundred seventeen patients were studied, measuring serum concentrations of interleukin (IL)1ß, IL2, IL4, IL5, IL6, IL10, IL12p70, IL13, IL18, granulocyte-macrophage colony-stimulating factor (GM-CSF), interferon (IFN) γ, and tumor necrosis factor (TNF) α. RESULTS: Significant differences were found between patients with severe AP and those with mild or moderately severe AP in IFN-γ (P < 0.001), IL6 (P < 0.001), TNF-α (P = 0.002), GM-CSF (P < 0.001), IL4 (P = 0.002), IL1b (P = 0.017), and IL13 (P < 0.001) concentrations. Interferon-γ, IL6, and TNF-α were associated with severe AP, whereas GM-CSF, IL4, IL1b, and IL13 were associated with mild or moderately severe AP. The IL13/IFNγ ratio was significantly higher in patients with mild AP (P = 7.36 × 10). CONCLUSIONS: A TH1 profile was associated with severe AP and a TH2 profile with mild or moderately severe AP. We report an IL13/IFNγ ratio of potential value to predict the prognosis in AP.

Genomic loss of HLA alleles may affect the clinical outcome in low-risk myelodysplastic syndrome patients.

The Revised International Prognostic Score and some somatic mutations in myelodysplastic syndrome (MDS) are independently associated with transformation to acute myeloid leukemia (AML). Immunity has also been implicated in the pathogenesis of MDS, although the underlying mechanism remains unclear. We performed a SNP array on chromosome 6 in CD34+ purified blasts from 19 patients diagnosed with advanced MDS and 8 patients with other myeloid malignancies to evaluate the presence of loss of heterozygosity (LOH) in HLA and its impact on disease progression. Three patients had acquired copy-neutral LOH (CN-LOH) on 6p arms, which may disrupt antigen presentation and act as a mechanism for immune system evasion. Interestingly, these patients had previously been classified at low risk of AML progression, and the poor outcome cannot be explained by the acquisition of adverse mutations. LOH HLA was not detected in the remaining 24 patients, who all had adverse risk factors. In summary, the clinical outcome of patients with advanced MDS might be influenced by HLA allelic loss, wich allows subclonal expansions to evade cytotoxic-T and NK cell attack. CN-LOH HLA may therefore be a factor favoring MDS progression to AML independently of the somatic tumor mutation load.

Molecular mechanisms underlying Grateloupia imbricata (Rhodophyta) carposporogenesis induced by methyl jasmonate.

When applied in vitro, methyl jasmonate is sensed by the red seaweed Grateloupia imbricate, substantially and visually affecting its carposporogenesis. However, although there is some understanding of the morphological changes induced by methyl jasmonate in vitro, little is known about the genes that are involved in red seaweed carposporogenesis and how their protein products act. For the work reported herein, the expression of genes in red seaweed that encode enzymes involved in the synthesis of methyl jasmonate (jasmonic acid carboxyl methyl transferase and a putative methyl transferase) was monitored. Additionally the genes involved in oxidation (cytochrome P450 and WD40), jasmonate synthesis, signal transduction, and regulation of reactive oxygen species (MYB), and reproduction (ornithine decarboxylase) were monitored. To determine when or if the aforementioned genes were expressed during cystocarp development, fertilized and fertile thalli were exposed to methyl jasmonate and gene expression was measured after 24 and 48 h. The results showed that methyl jasmonate promoted differential gene expression in fertilized thalli by 24 h and upregulated expression of the ornithine decarboxylase gene only by 48 h in fertile thalli (0.75 ± 003 copies · µL-1 at 24 h vs. 1.11 ± 0.04 copies · µL-1 at 48 h). We conclude that Ornithine decarboxylase expression involves methyl jasmonate signaling as well as development and maturation of cystocarps.

CD24 Expression Is Increased in 5-Fluorouracil-Treated Esophageal Adenocarcinoma Cells.

The cancer stem cell (CSC) model suggests that there are subsets of cells within a tumor with increased proliferation and self-renewal capacity, which play a key role in therapeutic resistance. The importance of cyclooxygenase-2 (COX-2) in carcinogenesis has been previously established and the use of COX-2 inhibitors as celecoxib has been shown to exert antitumor effects. The present study investigated whether treatment of esophageal adenocarcinoma (EAC) cells with 5-fluorouracil (5-FU) or the growth of tumor spheres increased the proportion of CSCs and also if treatment with celecoxib was able to reduce the putative CSC markers in this tumor. OE19 and OE33 EAC cells surviving 5-FU exposure exhibited an increase in CSC markers CD24 and ABCG2 and also an increased resistance to apoptosis. EAC cell lines had the capacity to form multiple spheres displaying typical CSC functionalities such as self-renewal and increased CD24 levels. In addition, after the induction of differentiation, cancer cells reached levels of CD24 similar to those observed in the parental cells. Treatment with celecoxib alone or in combination with 5-FU also resulted in a reduction of CD24 expression. Moreover, celecoxib inhibited the growth of tumor spheres. These findings showing a reduction in CSC markers induced by celecoxib suggest that the COX-2 inhibitor might be a candidate for combined chemotherapy in the treatment of EAC. However, additional clinical and experimental studies are needed.