IL28B genetic variation and cytomegalovirus-specific T-cell immunity in allogeneic stem cell transplant recipients.

A single nucleotide polymorphism (SNP), 3 kbp upstream of the IL28B gene (rs12979860; C/T), has been shown to influence the dynamics of cytomegalovirus (CMV) replication in allogeneic stem cell transplant recipients (Allo-SCT). We investigated whether this SNP had any effect on the dynamics of CMV-specific T-cell immunity in these patients. CMV pp65/IE-1 IFN-γ CD8+ and CD4+ T cells were enumerated by flow cytometry in 85 patients with no prior CMV DNAemia (group A) and in 57 after the onset of CMV DNAemia (group B). Donor IL28B genotype was determined by real-time PCR and plasma levels of IL-28B were quantitated by ELISA. CMV-specific T-cell counts and plasma IL-28B levels in patients in group A were not significantly different among the IL28B genotype groups. Patients harboring the donor IL28B T/T genotype appeared to expand CMV-specific IFN-γ CD8+ cells to a higher level in response to viral replication than their C/T and C/C counterparts. Fewer patients in the T/T group received pre-emptive antiviral therapy (P = 0.05). Overall, a significant inverse correlation was observed between median IL-28B levels measured prior to the CMV DNAemia onset and the level of CMV-specific CD8+ T cells enumerated after detection of CMV DNAemia (σ = -0.471; P = 0.013). In summary, the data suggested that the protective effect attributed to the rs12979860 SNP minor T allele could be mediated, at least in part, by eliciting robust CMV-specific T-cell responses. J. Med. Virol. 89:685-695, 2017. © 2016 Wiley Periodicals, Inc.

High salinity helps the halophyte Sesuvium portulacastrum in defense against Cd toxicity by maintaining redox balance and photosynthesis.

MAIN CONCLUSION: NaCl alleviates Cd toxicity in Sesvium portulacastrum by maintaining plant water status and redox balance, protecting chloroplasts structure and inducing some potential Cd (2+) chelators as GSH and proline. It has been demonstrated that NaCl alleviates Cd-induced growth inhibition in the halophyte Sesuvium portulacastrum. However, the processes that mediate this effect are still unclear. In this work we combined physiological, biochemical and ultrastructural studies to highlight the effects of salt on the redox balance and photosynthesis in Cd-stressed plants. Seedlings were exposed to different Cd concentrations (0, 25 and 50 µM Cd) combined with low (0.09 mM) (LS), or high (200 mM) NaCl (HS) in hydroponic culture. Plant-water relations, photosynthesis rate, leaf gas exchange, chlorophyll fluorescence, chloroplast ultrastructure, and proline and glutathione concentrations were analyzed after 1 month of treatment. In addition, the endogenous levels of stress-related hormones were determined in plants subjected to 25 µM Cd combined with both NaCl concentrations. In plants with low salt supply (LS), Cd reduced growth, induced plant dehydration, disrupted chloroplast structure and functioning, decreased net CO2 assimilation rate (A) and transpiration rate (E), inhibited the maximum potential quantum efficiency (Fv/Fm) and the quantum yield efficiency (Φ PSII) of PSII, and enhanced the non-photochemical quenching (NPQ). The addition of 200 mM NaCl (HS) to the Cd-containing medium culture significantly mitigated Cd phytotoxicity. Hence, even at similar internal Cd concentrations, HS-Cd plants were less affected by Cd than LS-Cd ones. Hence, 200 mM NaCl significantly alleviates Cd-induced toxicity symptoms, growth inhibition, and photosynthesis disturbances. The cell ultrastructure was better preserved in HS-Cd plants but affected in LS-Cd plants. The HS-Cd plants showed also higher concentrations of reduced glutathione (GSH), proline and jasmonic acid (JA) than the LS-Cd plants. However, under LS-Cd conditions, plants maintained higher concentration of salicylic acid (SA) and abscisic acid (ABA) than the HS-Cd ones. We conclude that in S. portulacastrum alleviation of Cd toxicity by NaCl is related to the modification of GSH and proline contents as well as stress hormone levels thus protecting redox balance and photosynthesis.

Incidence and dynamics of active cytomegalovirus infection in allogeneic stem cell transplant patients according to single nucleotide polymorphisms in donor and recipient CCR5, MCP-1, IL-10, and TLR9 genes.

Single nucleotide polymorphisms (SNPs) in genes involved in the activation or regulation of innate and adaptive immune responses may modulate the susceptibility to and the natural history of certain chronic viral infections. The current study aimed to investigate whether donor and recipient SNPs in the chemokine receptor 5 (rs1800023), monocyte chemoattractant protein 1 (rs13900), interleukin-10 (rs1878672), and Toll-like receptor 9 (rs352140) genes would exert any influence on the rate of incidence and features of CMV DNAemia in the allogeneic stem cell transplantation setting. This was a retrospective observational multicenter study. The cohort consisted of 102 non-consecutive allogeneic stem cell transplant recipients. SNP genotyping was performed by allele-specific real-time PCR. CMV surveillance was performed by the pp65 antigenemia assay/and or by real-time PCR. Seventy-three patients developed CMV DNAemia within the first 100 days after transplantation (71.5%). Neither donor nor recipient SNPs were associated significantly with the rate of incidence of active CMV infection, nor with the need for pre-emptive antiviral therapy. Both the duration of CMV DNAemia and the plasma CMV DNA peak load during episodes were significantly higher in patients harboring the donor (but not the recipient) chemokine receptor 5 A/A genotype, than in their A/G and G/G counterparts (P = 0.022 and P = 0.045, respectively). The data reported suggest that SNPs in chemokine receptor 5 may influence the dynamics of CMV infection in the Allo-SCT setting.

Detection of fungal DNA in peritoneal fluids by a PCR DNA low-density microarray system and quantitation of serum (1-3)-ß-D-glucan in the diagnosis of peritoneal candidiasis.

Microbiological documentation of peritoneal candidiasis (PC) is hampered by the low numbers of yeasts observable by direct microscopic examination and recoverable by culture methods. The performance of a polymerase chain reaction (PCR) DNA Low-Density Microarray System (CLART STIs B) was compared to that of BACTEC FX automated culture method for the detection of Candida spp. in 161 peritoneal fluids (PF) from patients with peritonitis. The clinical utility of (1-3)-ß-d-glucan (BDG) antigenemia in the diagnosis of PC was evaluated in 42 of these patients. The overall agreement between the PCR assay and the culture method was good (κ = 0.790), and their sensitivities were 93.5% and 74.19%, respectively. Serum BDG levels in patients with Candida spp. in PFs (median, 200.3 pg/mL; Range, 22.0-523.4 pg/mL) was significantly higher (P = 0.002) than those found in patients without the yeast (median, 25.3 pg/mL; Range, 0-523.4 pg/mL). Our study demonstrates the potential clinical utility of molecular methods and the measurement of serum BDG levels for the diagnosis of PC.

Effect of the IL28B Rs12979860 C/T polymorphism on the incidence and features of active cytomegalovirus infection in allogeneic stem cell transplant patients.

The current study was aimed at investigating whether the single nucleotide polymorphism (SNP) (rs12979860), upstream of the IL28B gene, had any effect on the incidence rate and the features of active CMV infection in the Allogeneic stem cell transplantation setting. This was a retrospective observational study including 151 patients undergoing T cell-replete Allo-SCT. Donor and recipient IL28 SNP genotype was determined by allele-specific real-time PCR. The incidence rate of active CMV infection was not significantly associated with either the donor or the recipient IL28B SNP genotype. Nevertheless, a trend towards a lower incidence of active CMV infection was noted in the donor T/T population with respect to the donor C/T and C/C population. The duration of first episodes of CMV DNAemia was significantly shorter in patients carrying the donor T/T genotype with respect to their C/C or C/T counterparts (P = 0.038). Peak CMV DNAmeia levels tended to be lower in patients carrying the T/T genotype (donor or recipient) than in C/C or C/T patients, although statistical significance was not reached. In conclusion the data presented pointed to a protective effect of the T allele (recessive genetic model) against CMV infection in the Allo-SCT setting.

Expression of nutrient transporters in placentas affected by gestational diabetes: role of leptin.

Gestational diabetes mellitus (GDM) is the most frequent pathophysiological state of pregnancy, which in many cases produces fetuses with macrosomia, requiring increased nutrient transport in the placenta. Recent studies by our group have demonstrated that leptin is a key hormone in placental physiology, and its expression is increased in placentas affected by GDM. However, the effect of leptin on placental nutrient transport, such as transport of glucose, amino acids, and lipids, is not fully understood. Thus, we aimed to review literature on the leptin effect involved in placental nutrient transport as well as activated leptin signaling pathways involved in the expression of placental transporters, which may contribute to an increase in placental nutrient transport in human pregnancies complicated by GDM. Leptin appears to be a relevant key hormone that regulates placental transport, and this regulation is altered in pathophysiological conditions such as gestational diabetes. Adaptations in the placental capacity to transport glucose, amino acids, and lipids may underlie both under- or overgrowth of the fetus when maternal nutrient and hormone levels are altered due to changes in maternal nutrition or metabolic disease. Implementing new strategies to modulate placental transport may improve maternal health and prove effective in normalizing fetal growth in cases of intrauterine growth restriction and fetal overgrowth. However, further studies are needed to confirm this hypothesis.

Different effects of aluminum on the actin cytoskeleton and brefeldin A-sensitive vesicle recycling in root apex cells of two maize varieties differing in root elongation rate and aluminum tolerance.

A relationship between aluminum (Al) toxicity, endocytosis, endosomes and vesicle recycling in the root transition zone has recently been demonstrated. Here the importance of filamentous actin (F-actin)-based vesicle trafficking for Al tolerance has been investigating in maize varieties differing in their Al sensitivities. More Al was internalized into root tip cells of the Al-sensitive variety 16x36 than in the Al-tolerant variety Cateto. The actin cytoskeleton and vesicle trafficking were primary targets for Al toxicity in the root tips of the sensitive variety. Visualization of boron-cross-linked rhamnogalacturonan II (RGII)-containing brefeldin A (BFA) compartments revealed that Al inhibited the formation of these compartments, especially in variety 16x36. The time sequence of Al effects on pectin recycling matches the growth effects of Al in this sensitive variety. These results support the hypothesis that Al binding to pectin-rich cell walls can contribute to reversible inhibition of root elongation. Al-induced alterations on F-actin were most evident in the central part of the transition zone of Al-sensitive 16x36, where Al was localized inside the nucleoli. In relation to this observation, a role for symplastic Al in both irreversible growth inhibition and amelioration of BFA-induced inhibition of root elongation is discussed.

Boron-induced amelioration of aluminium toxicity in a monocot and a dicot species.

Previous research has reported inconsistent results from experiments on the influence of boron (B) on plant sensitivity to potentially toxic aluminium (Al) concentrations. Differences in B requirement and cell wall properties among species, especially between Poaceae and dicots, may account for this. This investigation reports amelioration by B of Al-induced inhibition of root elongation in Al-sensitive cucumber (Cucumis sativus), but not in Al-sensitive maize (Zea mays). Vital staining, however, also revealed a positive influence of B supply on Al tolerance in maize. In both species, adequate B supply decreased Al-induced damage of cell integrity. In cucumber, increasing B supply enhanced Al concentrations and haematoxylin staining in root tips. In maize, no differences for root Al among B treatments were observed. These results indicate that the positive effect of B on Al resistance was not due to less Al accumulation in root tips. Enhanced concentrations of reduced glutathione were found in roots of Al-stressed maize plants growing with adequate B. It is concluded that adequate B supply is essential for prevention of Al toxicity in both the dicot and the monocot species. In dicot cucumber, the B-induced amelioration of root elongation, despite higher Al accumulation in root tips, indicates B-induced change in either or both Al speciation and compartmentation in the tips. The protection by an adequate B supply of roots against Al-induced cell death suggests a role for B in the defence against oxidative stress. This is supported by the observation that Al induced enhanced levels of GSH in roots of maize plants growing with adequate B supply but not in those growing with either deficient or excess B concentrations.

A glance into aluminum toxicity and resistance in plants.

Aluminum toxicity is an important stress factor for plants in acidic environments. During the last decade considerable advances have been made in both techniques to assess the potentially toxic Al species in environmental samples, and knowledge about the mechanisms of Al toxicity and resistance in plants. After a short introduction on Al risk assessment, this review aims to give an up-to-date glance into current developments in the field of Al toxicity and resistance in plants, also providing sufficient background information for non-specialists in aluminum research. Special emphasis is paid to root growth and development as primary targets for Al toxicity. Mechanisms of exclusion of Al from sensitive root tips, as well as tolerance of high Al tissue levels are considered.

Epidemiology of invasive candidiasis in a surgical intensive care unit: an observational study.

BACKGROUND: Invasive candidiasis (IC) is a frequent and life-threatening infection in critically ill patients. The aim of this study was to evaluate the epidemiology of IC and the antifungal susceptibility of etiological agents in patients admitted to our surgical intensive care unit (SICU) in Spain. METHODS: We designed a prospective, observational, single center, population-based study in a SICU. We included all consecutive adult patients (≥18 years old) who had documented IC, either on admission or during their stay, between January 2012 and December 2013. RESULTS: There were a total of 22 episodes of IC in the 1149 patients admitted during the 24-month study. The overall IC incidence was 19.1 cases per 1000 admissions. Thirteen cases of IC (59.1%) were intra-abdominal candidiasis (IAC) and 9 (40.9%) were candidemias. All cases of IAC were patients with secondary peritonitis and severe sepsis or septic shock. The overall crude mortality rate was 13.6%; while, it was 33% in patients with candidemia. All patients with IAC survived, including one patient with concomitant candidemia. The most common species causing IC was Candida albicans (13; 59.1%) followed by Candida parapsilosis (5; 22.7%), and Candida glabrata (2; 9.1%). There was also one case each (4.5%) of Candida krusei and Candida tropicalis. Thus, the ratio of non-C. albicans (9) to C. albicans (13) was 1:1.4. There was resistance to fluconazole and itraconazole in 13.6% of cases. Resistance to other antifungals was uncommon. CONCLUSIONS: Candida parapsilosis was the second most common species after C. albicans, indicating the high prevalence of non-C. albicans species in the SICU. Resistance to azoles, particularly fluconazole, should be considered when starting an empirical treatment. Although IAC is a very frequent form of IC in critically ill surgical patients, prompt antifungal therapy and adequate source control appears to lead to a good outcome. However, our results are closely related to our ICU and any generalization must be taken with caution. Therefore, further investigations are needed.

Evaluation of the Architect Epstein-Barr Virus (EBV) viral capsid antigen (VCA) IgG, VCA IgM, and EBV nuclear antigen 1 IgG chemiluminescent immunoassays for detection of EBV antibodies and categorization of EBV infection status using immunofluorescence assays as the reference method.

Commercial immunoassays for detecting IgG and IgM antibodies against Epstein-Barr virus (EBV), viral capsid antigens (VCA), and IgGs toward EBV nuclear antigen-1 (EBNA-1) are routinely used in combination to categorize EBV infection status. In this study, we evaluated the performances of the Architect EBV VCA IgG, VCA IgM, and EBNA-1 IgG chemiluminescent microparticle assays (CMIAs) in EBV serological analyses using indirect immunofluorescence assays and anticomplement immunofluorescence assays as the reference methods for VCA IgG, VCA IgM, and EBNA-1 IgG antibody detection, respectively. A total of 365 serum samples representing different EBV serological profiles were included in this study. The κ values (concordances between the results) obtained in the Architect CMIA and those in the reference assays were 0.905 (P < 0.0001) for VCA IgM, 0.889 (P < 0.0001) for VCA IgG, and 0.961 (P < 0.0001) for EBNA-1 IgG. The sensitivities and specificities were, respectively, 91.08% and 99.48% for VCA IgM, 99.23% and 86.27% for VCA IgG, and 96.77% and 99.16% for EBNA-1 IgG. The sensitivities and specificities of the Architect CMIA panel were, respectively, 99.15% and 98.6% for diagnosing a primary infection, 97.62% and 93.39% for diagnosing a past EBV infection, and 92.42% and 97.82% for diagnosing the absence of an EBV infection. In summary, we demonstrated that the Architect EBV antibody panel performs very well for EBV antibody detection and correctly categorizes clinically relevant EBV infection states.

Artritis séptica: a propósito de un caso / Septic arthritis: A case report

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Valores de plomo y arsénico en hígado, riñon, bazo y cerebro de sujetos aparentemente sanos / Lead and arsenic value in liver, kidney, spleen and brain in human beings

La investigación se realizó de 25 cadáveres (16 hombres y 9 mujeres) procedentes de la Morgue Central de Lima, con edades comprendidas entre 18-25 años. la destrucción de la muestra se realizó por el método sulfonetrico. Las concentraciones de Pb, arsénico se obtuvieron empleando lé espectrofotométrico por absorción atómica y de vasos y sedivec respectivamente. Las concentraciones medias de plomo, arsénico en higado fueron: 86.96 ug por ciento, 11.83 ug por ciento y C.E 54.61-113/19, 4.79-18.88 respectivamente; en riñon fueron 75.17 ug por ciento y C.E 50.97-109-15, 361-16-37 respectivamente; en bazo fueron; 63.18 ug por ciento, 4 ug por ciento y L.E. 30.37-92.99, 086-846 respectivamente, en cerebro fueron: 22 ug por ciento, 0.05 por ciento y C.E. 4.11-40.47 0.01 respectivamente. Las cifras promedios encontrados coinciden con algunos "valores normales" reportados por estos investigadores de estos países.