Higher Immune Response Research Articles

Hybrid immunity versus vaccine-induced immunity against SARS-CoV-2 in patients with autoimmune rheumatic diseases.

Hybrid immunity versus vaccine-induced immunity against SARS-CoV-2 in patients with autoimmune rheumatic diseases.

CTIM-03. AUTOLOGOUS ADOPTIVE IMMUNE-CELL THERAPY ELICITED A DURABLE RESPONSE WITH ENHANCED IMMUNE REACTION SIGNATURES IN PATIENTS WITH RECURRENT GLIOBLASTOMA: AN OPEN LABEL, PHASE I/IIA TRIAL

Abstract Glioblastoma multiforme (GBM) is an aggressive malignancy classified by the World Health Organization as a grade IV glioma. Despite the availability of aggressive standard therapies, most patients experience recurrence, for which there are currently no effective treatments. We aimed to conduct a phase I/IIa clinical trial to investigate the safety and efficacy of adoptive, ex-vivo-expanded, and activated natural killer cells and T lymphocytes from peripheral blood mononuclear cells of patients with recurrent GBM. This study was a single-arm, open-label, investigator-initiated trial on 14 patients recruited between 2013 and 2017. The immune cells were administered via intravenous injection 24 times at 2-week intervals after surgical resection or biopsy. The safety and clinical efficacy of this therapy was examined by assessing adverse events and comparing 2-year overall survival (OS). Transcriptomic analysis of tumor tissues was performed using NanoString to identify the mechanism of therapeutic efficacy. No grade 4 or 5 severe adverse events were observed. The most common treatment-related adverse events were grade 1 or 2 in severity. The most severe adverse event was grade 3 fever. Median OS was 22.5 months, and the median progression-free survival was 10 months. Five patients were alive for over 2 years and showed durable response with enhanced immune reaction transcriptomic signatures without clinical decline until the last follow-up after completion of the therapy. In conclusion, autologous adoptive immune-cell therapy was safe and showed durable response in patients with enhanced immune reaction signatures. This therapy may be effective for recurrent GBM patients with high immune response in their tumor microenvironments. Trial registration: The Korea Clinical Research Information Service database: KCT0003815, Registered 18 April 2019, retrospectively registered.

The Effect of Exosomes Derived from Unrestricted Somatic Stem Cells on Murine Model of Sepsis

Sepsis is a systemic infection mainly caused by bacterial infections. Despite all efforts and advances in the treatment of sepsis, it is still considered one of the leading causes of death in hospitalized patients. Today, we have to use novel therapies and one of the most important is cell-free therapy. Exosomes have been shown to contain the contents of their parent cells and that they do not generate an immune response between different individuals which makes them a good candidate for transplantation. Unrestricted somatic stem cells (USSC), also known as mesenchymal stem cell progenitors due to their high proliferative capacity and low immune response, may be a novel therapy for sepsis. In this study, the effect of USSC-derived exosomes on sepsis was investigated using a mouse model. USSCs were isolated from human cord blood and characterized by flow cytometry and multi-lineage differentiation. The exosomes were then harvested from USSCs and characterized by transmission electron microscopy, Western blotting, and dynamic light scattering. The harvested exosomes were injected into the mouse model of sepsis. Biochemical, histological, molecular, and survival studies were performed in different groups. Our observations showed that USSC-derived exosomes can reduce inflammation in septic mice. Histopathologic and biochemical findings in the sham group showed multiorgan involvement, but these changes disappeared after 7 days of exosome administration. Moreover, the expression of IRAK-1 and TRAF-6 (main adapter molecules in signaling pathways of inflammation) was decreased through negative regulation by miR-146a after 72 h of exosome administration. A 2-fold increase in the level of IL-10 and a 2-fold decrease in the levels of IL-6 and TNF-α was observed. In conclusion, we showed that direct injection of USSC-derived exosomes can be one of the important methods for the treatment of various aspects of sepsis due to their immunomodulatory properties.

Cationic and Biocompatible Polymer/Lipid Nanoparticles as Immunoadjuvants.

Nanostructures have been of paramount importance for developing immunoadjuvants. They must be cationic and non-cytotoxic, easily assembling with usually oppositely charged antigens such as proteins, haptens or nucleic acids for use in vaccines. We obtained optimal hybrid nanoparticles (NPs) from the biocompatible polymer poly(methyl methacrylate) (PMMA) and the cationic lipid dioctadecyl dimethyl ammonium bromide (DODAB) by emulsion polymerization of methyl methacrylate (MMA) in the presence of DODAB. NPs adsorbed ovalbumin (OVA) as a model antigen and we determined their adjuvant properties. Interestingly, they elicited high double immune responses of the cellular and humoral types overcoming the poor biocompatibility of DODAB-based adjuvants of the bilayer type. The results suggested that the novel adjuvant would be possibly of use in a variety of vaccines.

In vitro analysis of human immune response (IgG) against salivary gland extract of dengue vector from dengue hemorrhagic fever (DHF) endemic area in Jember, Indonesia

The mosquito species Ae. aegyptiand Ae. albopictusare two potential vectors of dengue fever. The salivary glands of these species contain substances that play a role in the transmission of pathogens. These include vasodilators and immunomodulatory compounds. Immunomodulatory components can modulate the host immune system by producing specific antibodies (IgG). This study aims to investigate the human immune response (IgG) against the salivary gland extract of Ae. aegyptiand Ae. albopictus. Samples were collected from individuals who were Dengue patients, as well as healthy individuals and neonates from the Jember endemic area. Results show that the levels of IgG response vary across the individual. Generally, Dengue patients and healthy people in the DHF-endemic area had higher levels of IgG. The highest immune response was found in DHF patients, followed by healthy persons, and finally the neonate samples, respectively.

PSXI-8 Heritability estimates of antibody- and cell-mediated immune response in north American angus beef cattle

Abstract Including immune response traits in breeding programs has been suggested as a solution to improve overall animal health and enhance disease resistance but is not yet available for Angus cattle in North America. One way to measure immune response is to use the High Immune Response (HIR™) technology, which identifies animals with superior heritable immunity by evaluating antibody-mediated (AMIR) and cell-mediated (CMIR) immune response, allowing for the calculation of an estimated breeding value for total adaptive immune response for each animal. Before HIR™ can be included in beef cattle breeding programs, genetic parameters, including heritability, must be estimated for the traits involved. The objective of this study was to estimate a preliminary heritability for AMIR and CMIR in North American Angus beef cattle. On day 0 of the phenotyping protocol, cattle were immunized intramuscularly with a preparation of type 1 (CMIR) and type 2 (AMIR) antigens with adjuvant. On day 14, cattle received an intradermal injection of 0.1 mL of the CMIR test antigen in the right tail fold, and 0.1 mL PBS in the left tail fold. Change in cutaneous double skinfold thickness after 24 hours was used to assess CMIR. Blood was collected on days 0 and 14 to evaluate serum antibody to the type 2 antigen by ELISA to quantify AMIR. Heritability estimates were calculated for Canada and the USA separately, and then for both countries combined using single-trait animal models in ASReml and are presented in Table 1. The results of this study indicate that the heritabilities of AMIR and CMIR are moderate and emphasize the potential for its inclusion into Angus breeding schemes.

Preparation of an Inactivated Peste des Petits Ruminants Vaccine and Its Comparative Immunogenicity Evaluation in an Animal Model.

Peste des petits ruminants (PPR) is a highly contagious disease that is considered a major threat to the small livestock industry. Although vaccination via live-attenuated PPR vaccine is a main controlling strategy in the endemic area, during PPR eradication process, the inactivated PPR vaccine (iPPRV) is recommended. This study aimed to compare the inactivation kinetics of the PPR virus via different inactivants and immunogenicity evaluations of the iPPRV formulated vaccine in mice. The vaccinal live PPR virus was inactivated by either H2O2 or binary ethylenimine (BEI (at two concentrations of 1 or 4 mM. Thereafter, the inactivated virus was formulated with different adjuvants, including aluminum hydroxide (AH), aluminum phosphate (AP), and a mixture of AH and AP that were intraperitoneally (IP) administrated (0.1 mL) to 90 BALB/c mice in a completely randomized design and 3×3 factorial arrangement (9 animals per group). The booster vaccination was carried out in all animals 21 days after the primary vaccination. Results showed that the PPR virus was successfully inactivated by all the inactivation agents; however, the time of complete virus inactivation was estimated to be 482, 295, and 495 min post-treatment initiation for 1 mM BEI, 4 mM BEI, and H2O2, respectively. The main effect of inactivant on antibody titers against PPR virus that was measured after 42days post-immunization in mice was significant (P<0.05); however, the adjuvant and interaction effect of inactivator×adjuvant were not effective(P>0.05). Inactivation by 1 mM BEI was associated with a higher antibody titer against PPR virus (P<0.05) in comparison with both 4 mM BEI and H2O2 (2.51 vs. 2.25 and 2.22, respectively). Meanwhile, there were no significant differences among the used adjuvants in terms of eliciting antibody response against PPR virus. In conclusion, the use of 1 mM BEI in combination of AH, AP, or a mixture of AH and AP was associated with a higher immune response against PPR virus in mice. However, the appropriate inactivation kinetic of the virus and immunogenicity associated with the use of H2O2, as well as its biocompatibility property and better cost-benefit, nominated H2O2 to be used in iPPR preparation; however, more investigations are required in target animals.

SARS-CoV-2 IgG Antibody Response after Immunization of Healthcare Workers with Inactivated COVID-19 Vaccine (CoronaVac) at Phyathai 3 Hospital

OBJECTIVES: To evaluate the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) anti-spike Immunoglobulin G (IgG) antibody response after CoronoVac immunization of healthcare workers at Phyathai 3 Hospital. MATERIALS AND METHODS: The descriptive study was performed at Phyathai 3 Hospital between March 2021 and May 2021. Healthcare workers who received two doses (three weeks apart) of the CoronaVac vaccine were included. Blood samples for anti-spike IgG antibodies were taken from each healthcare worker before getting vaccinated and four weeks after completing two doses of the vaccine. RESULT: A total of 88 healthcare workers were enrolled in our study. Fifty-three (60%) of them were female, 84(95%) were physicians, 46(52%) were obese and 33(37.5%) had at least one coexisting condition. The mean age was 45.8 ± 9.3 years. Seven (8%) of participants were older than 60 years of age. All participants did not have IgG antibodies at baseline. Eighty-seven (98.9%) healthcare workers had seroconversion of anti-spike IgG antibodies four weeks after completing two doses of the CoronaVac vaccine. The mean level of anti-spike IgG at four weeks after completing vaccination was 115+/-85 unit/ml (range, 1.77-297.3 unit/ml). Anti-spike IgG levels were significantly higher in females than males (p = 0.02). Normal-weight participants showed higher anti-spike IgG levels than obese individuals (p = 0.01). IgG antibody responses tended to decrease with age. The highest IgG levels were observed in the ages of 30-40 years. CONCLUSION: Two doses of the CoronaVac vaccine could induce a 98.9% rate of seroconversion in healthcare workers. Female and normal-weight participants were significantly associated with a higher level of IgG response. Younger adults had a higher immune response than older adults in our setting.

Ineffective humoral anti-tick IgY-response in birds: reaction against pathogen constituents?

Background: Variation in parasite burdens among hosts is typically related to differences in adaptive immunity. Comprehension of underlying mechanisms is hence necessary to gain better insights into endemic transmission cycles. Here we investigate whether wild songbirds that have never been exposed to ticks develop adaptive humoral immunity against endemic Ixodes ricinus ticks. Methods: Blue tits were exposed three times in succession to wild Ixodes ricinus ticks. For each infestation, serum samples were obtained. An enzyme-linked immunosorbent assay was developed, using tick salivary antigens, in order to quantify the bird's IgY response against ticks. In addition, at every sampling occasion the birds' body weight (corrected for body size) and haematocrit level was determined. Results: Individual IgY levels against the ticks' salivary proteins increased over three consecutive tick infestations, and large among-individual variation was observed. The responses were specifically directed against I. ricinus; cross-reactivity against the congeneric tree-hole tick Ixodes arboricola was negligibly low. IgY responses did not impinge on tick feeding success (engorgement weight and attachment success). Yet, those birds with the highest immune responses were more capable to reduce the acute harm (blood depletions) by compensating erythrocyte loss. Furthermore, at the end of the experiment, these birds had gained more body weight than birds with lower IgY levels. Conclusions: Latter observations can be considered as an effect of host quality and/or tolerance mechanisms. Birds anticipate the (future) costs of the activation of the immune system by ticks and/or ongoing tick-borne pathogen infections. Furthermore, although unsuccessful against tick feeding, the IgY responses may indirectly protect birds against tick-borne disease by acting against salivary protein secretions on which pathogens rely for transmission.

A Comprehensive Prognostic and Immunological Analysis of a Six-Gene Signature Associated With Glycolysis and Immune Response in Uveal Melanoma.

Uveal melanoma (UM) is a subtype of melanoma with poor prognosis. This study aimed to construct a new prognostic gene signature that can be used for survival prediction and risk stratification of UM patients. In this work, transcriptome data from the Molecular Signatures Database were used to identify the cancer hallmarks most relevant to the prognosis of UM patients. Weighted gene co-expression network, univariate least absolute contraction and selection operator (LASSO), and multivariate Cox regression analyses were used to construct the prognostic gene characteristics. Kaplan–Meier and receiver operating characteristic (ROC) curves were used to evaluate the survival predictive ability of the gene signature. The results showed that glycolysis and immune response were the main risk factors for overall survival (OS) in UM patients. Using univariate Cox regression analysis, 238 candidates related to the prognosis of UM patients were identified (p < 0.05). Using LASSO and multivariate Cox regression analyses, a six-gene signature including ARPC1B, BTBD6, GUSB, KRTCAP2, RHBDD3, and SLC39A4 was constructed. Kaplan–Meier analysis of the UM cohort in the training set showed that patients with higher risk scores had worse OS (HR = 2.61, p < 0.001). The time-dependent ROC (t-ROC) curve showed that the risk score had good predictive efficiency for UM patients in the training set (AUC > 0.9). Besides, t-ROC analysis showed that the predictive ability of risk scores was significantly higher than that of other clinicopathological characteristics. Univariate and multivariate Cox regression analyses showed that risk score was an independent risk factor for OS in UM patients. The prognostic value of risk scores was further verified in two external UM cohorts (GSE22138 and GSE84976). Two-factor survival analysis showed that UM patients with high hypoxia or immune response scores and high risk scores had the worst prognosis. Moreover, a nomogram based on the six-gene signature was established for clinical practice. In addition, risk scores were related to the immune infiltration profiles. Taken together, this study identified a new prognostic six-gene signature related to glycolysis and immune response. This six-gene signature can not only be used for survival prediction and risk stratification but also may be a potential therapeutic target for UM patients.

Synthetic Pseudaminic-Acid-Based Antibacterial Vaccine Confers Effective Protection against Acinetobacter baumannii Infection.

Acinetobacter baumannii exhibits resistance to most first-line antibiotics; thus, development of new antibacterial agents is urgently required. Pseudaminic acid exists as the surface glycan of A. baumannii. In this study, we chemically synthesized pseudaminic acid, conjugated it to carrier protein CRM197 using the OPA (ortho-phthalaldehyde) chemistry, and obtained three Pse–CRM197 conjugates with different Pse loadings. These Pse–CRM197 conjugates were found to stimulate high immune responses in mice, which protected the vaccinated mice from infections caused by Pse-producing A. baumannii. Our data indicate that chemically synthesized Pse–CRM197 conjugates can be developed into vaccines against Pse-bearing pathogens, thus offering a feasible alternative for the control of clinical infections caused by multidrug-resistant (MDR) A. baumannii, for which current treatment options are extremely limited.

Immune reconstitution inflammatory syndrome in non-HIV cryptococcal meningitis: Cross-talk between pathogen and host.

BackgroundCryptococcal meningitis (CM)‐associated immune reconstitution inflammatory syndrome (IRIS) is associated with high mortality, the epidemiology and pathophysiology of which is poorly understood, especially in non‐HIV populations.ObjectivesWe aim to explore the incidence, clinical risk factors, immunological profiles and potential influence of leukotriene A4 hydroxylase (LTA4H) on non‐HIV CM IRIS populations.MethodsIn this observational cohort study, 101 previously untreated non‐HIV CM patients were included. We obtained data for clinical variables, 27 cerebrospinal fluid (CSF) cytokines levels and LTA4H genotype frequencies. Changes of CSF cytokines levels before and at IRIS occurrence were compared.ResultsImmune reconstitution inflammatory syndrome was identified in 11 immunocompetent males, generating an incidence of 10.9% in non‐HIV CM patients. Patients with higher CrAg titres (> 1:160) were more likely to develop IRIS, and titre of 1:1280 is the optimum level to predict IRIS occurrence. Baseline CSF cytokines were significantly higher in IRIS group, which indicated a severe host immune inflammation response. Four LTA4H SNPs (rs17525488, rs6538697, rs17525495 and rs1978331) exhibited significant genetic susceptibility to IRIS in overall non‐HIV CM, while five cytokines were found to be associated with rs1978331, and baseline monocyte chemotactic protein 1 (MCP‐1) became the only cytokine correlated with both IRIS and LTA4H SNPs.ConclusionsOur study suggested that non‐HIV CM patients with high fungal burden and severe immune inflammation response were more likely to developed IRIS. LTA4H polymorphisms may affect the pathogenesis of IRIS by regulating the level of baseline CSF MCP‐1.

Two doses of SARS-CoV-2 vaccination induce robust immune responses to emerging SARS-CoV-2 variants of concern

The extent to which immune responses to natural infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and immunization with vaccines protect against variants of concern (VOC) is of increasing importance. Accordingly, here we analyse antibodies and T cells of a recently vaccinated, UK cohort, alongside those recovering from natural infection in early 2020. We show that neutralization of the VOC compared to a reference isolate of the original circulating lineage, B, is reduced: more profoundly against B.1.351 than for B.1.1.7, and in responses to infection or a single dose of vaccine than to a second dose of vaccine. Importantly, high magnitude T cell responses are generated after two vaccine doses, with the majority of the T cell response directed against epitopes that are conserved between the prototype isolate B and the VOC. Vaccination is required to generate high potency immune responses to protect against these and other emergent variants.

Radiation-Inactivated S. gallinarum Vaccine Provides a High Protective Immune Response by Activating Both Humoral and Cellular Immunity.

Salmonella enterica subsp. enterica serovar Gallinarum (SG) is a common pathogen in chickens, and causes an acute systemic disease that leads to high mortality. The live attenuated vaccine 9R is able to successfully protect chickens older than six weeks by activating a robust cell-mediated immune response, but its safety and efficacy in young chickens remains controversial. An inactivated SG vaccine is being used as an alternative, but because of its low cellular immune response, it cannot be used as a replacement for live attenuated 9R vaccine. In this study, we employed gamma irradiation instead of formalin as an inactivation method to increase the efficacy of the inactivated SG vaccine. Humoral, cellular, and protective immune responses were compared in both mouse and chicken models. The radiation-inactivated SG vaccine (r-SG) induced production of significantly higher levels of IgG2b and IgG3 antibodies than the formalin-inactivated vaccine (f-SG), and provided a homogeneous functional antibody response against group D, but not group B Salmonella. Moreover, we found that r-SG vaccination could provide a higher protective immune response than f-SG by inducing higher Th17 activation. These results indicate that r-SG can provide a protective immune response similar to the live attenuated 9R vaccine by activating a higher humoral immunity and a lower, but still protective, cellular immune response. Therefore, we expect that the radiation inactivation method might substitute for the 9R vaccine with little or no side effects in chickens younger than six weeks.

Yeast cell surface displaying VP28 antigen and its potential application for shrimp farming

VP28 is an envelope protein of White Spot Syndrome Virus (WSSV), which has been shown in previous studies to induce a high immune response in shrimp. VP28 has been produced in some host systems such as Escherichia coli, Bacillus subtilis, and Pichia pastoris as free protein. Here we showed a new strategy of anchoring VP28 on the Saccharomyces cerevisiae yeast surface and using the yeast cell extract combined with probiotic as an oral vaccine for shrimp farming. We have successfully constructed a recombinant yeast cell capable of expressing VP28 on the cell surface. The feeding diet combined with VP28 anchored yeast cell extract provided significant assurance to Litopenaeus vannamei, challenged by WSSV, resulting in a relative percent survival (RPS) of 87.10 ± 2.15%. Interestingly, the utilization of VP28 anchored yeast cell extract could enhance the efficiency of probiotic strains like Lactobacillus and Bacillus on shrimp farming. The results in both laboratory scales and field trials using extract of VP28 displaying Saccharomyces showed a growth-promoting effect in shrimp, assessed through average shrimp weight. Taken together, our results in this study demonstrated a new successful strategy of using yeast cell surface as a tool to produce VP28-based oral vaccine for shrimp aquaculture. KEY POINTS: • A new strategy of using VP28 antigen as anchored protein on S. cerevisiae yeast cell surface (S. cerevisiae::VP28) • The utilization of VP28 antigen and yeast as S. cerevisiae::VP28 extract enhanced potential protection of Litopenaeus vannamei against White Spot Syndrome Virus (RPS 87.10%) • The use of S. cerevisiae::VP28 extract increased efficiency of probiotic on shrimp growth-promoting effect either lab-scale or field trial.

Antibody response after one and two jabs of the BNT162b2 vaccine in nursing home residents: The CONsort‐19 study

BackgroundThe humoral immune response following COVID‐19 vaccination in nursing home residents is poorly known. A longitudinal study compared levels of IgG antibodies against the spike protein (S‐RBD IgG) (S‐RDB protein IgG) after one and two BNT162b2/Pfizer jabs in residents with and without prior COVID‐19.MethodsIn 22 French nursing homes, COVID‐19 was diagnosed with real‐time reverse‐transcriptase polymerase chain reaction (RT‐PCR) for SARS‐CoV‐2. Blood S‐RDB‐protein IgG and nucleocapsid (N) IgG protein (N‐protein IgG) were measured 21–24 days after the first jab (1,004 residents) and 6 weeks after the second (820 residents).ResultsIn 735 residents without prior COVID‐19, 41.7% remained seronegative for S‐RDB‐protein IgG after the first jab vs. 2.1% of the 270 RT‐PCR‐positive residents (p < 0.001). After the second jab, 3% of the 586 residents without prior COVID‐19 remained seronegative. However, 26.5% had low S‐RDB‐protein IgG levels (50–1050 UA/ml) vs. 6.4% of the 222 residents with prior COVID‐19. Residents with an older infection (first wave), or with N‐protein IgG at the time of vaccination, had the highest S‐RDB‐protein IgG levels. Residents with a prior COVID‐19 infection had higher S‐RDB‐protein IgG levels after one jab than those without after two jabs. InterpretationA single vaccine jab is sufficient to reach a high humoral immune response in residents with prior COVID‐19. Most residents without prior COVID‐19 are seropositive for S‐RDB‐protein IgG after the second jab, but around 30% have low levels. Whether residents with no or low post‐vaccine S‐RDB protein IgG are at higher risk of symptomatic COVID‐19 requires further analysis.

Next-Generation Bioinformatics Approaches and Resources for Coronavirus Vaccine Discovery and Development-A Perspective Review.

COVID-19 is a contagious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). To fight this pandemic, which has caused a massive death toll around the globe, researchers are putting efforts into developing an effective vaccine against the pathogen. As genome sequencing projects for several coronavirus strains have been completed, a detailed investigation of the functions of the proteins and their 3D structures has gained increasing attention. These high throughput data are a valuable resource for accelerating the emerging field of immuno-informatics, which is primarily aimed toward the identification of potential antigenic epitopes in viral proteins that can be targeted for the development of a vaccine construct eliciting a high immune response. Bioinformatics platforms and various computational tools and databases are also essential for the identification of promising vaccine targets making the best use of genomic resources, for further experimental validation. The present review focuses on the various stages of the vaccine development process and the vaccines available for COVID-19. Additionally, recent advances in genomic platforms and publicly available bioinformatics resources in coronavirus vaccine discovery together with related immunoinformatics databases and advances in technology are discussed.

Next Generation Immunotherapies – Emerging Strategies for Immune Modulation against Cancer, Infections, and Beyond

Next Generation Immunotherapies – Emerging Strategies for Immune Modulation against Cancer, Infections, and Beyond

Detrimental effects of urbanization on the diet, health, and signal coloration of an ecologically successful alien bird

Theory suggests that overcrowding and increased competition in urban environments might be detrimental to individual condition in avian populations. Unfavourable living conditions could be compounded by changes in dietary niche with additional consequences for individual quality of urban birds. We analysed the isotopic signatures, signal coloration, body condition, parasitic loads (feather mites and coccidia), and immune responsiveness of 191 adult common (Indian) mynas (Acridotheres tristis) captured in 19 localities with differing levels of urbanization. The isotopic signature of myna feathers differed across low and high urbanized habitats, with a reduced isotopic niche breadth found in highly urbanized birds. This suggests that birds in high urban environments may occupy a smaller foraging niche to the one of less urbanized birds. In addition, higher degrees of urbanization were associated with a decrease in carotenoid-based coloration, higher ectoparasite loads and higher immune responsiveness. This pattern of results suggests that the health status of mynas from more urbanized environments was poorer than mynas from less modified habitats. Our findings are consistent with the theory that large proportions of individual birds that would otherwise die under natural conditions survive due to prevailing top-down and bottom-up ecological processes in cities. Detrimental urban ecological conditions and search for more favourable, less crowded habitats offers the first reasonable explanation for why an ecological invader like the common myna continues to spread within its global invasive range.

High Levels of Serum IgG for Opisthorchis viverrini and CD44 Expression Predict Worse Prognosis for Cholangiocarcinoma Patients after Curative Resection.

BackgroundOpisthorchis viverrini (OV)-associated cholangiocarcinoma (CCA) has a high immune response with chronic inflammation and oxidative stress. CD44 and Nestin, two cancer stem cell (CSC) markers, play major roles in cancer cell survival. Effects of immune response and expression CSC markers on survival of patients with CCA remain unclear.ObjectiveTo investigate the effects of level of OV IgG together with CSC marker expression and also the combination of these markers on survival of CCA patients after curative resection.MethodsAll serum specimens from CCA patients who underwent curative surgery from 2005 to 2015 were examined for IgG for OV antigen by ELISA. Tissue specimens were studied for CD44 and Nestin expression. Survival analysis by Cox proportional hazard model was used for estimating hazard ratio (HR) with a 95% confidence interval (CI).ResultsIn this study, 122 (69.3%) of 176 were positive for OV IgG, and 35 (19.9%) were considered to have high-positive OV IgG. CD44s positive expression was found in 54 (40%), CD44v6 high expression in 96 (69.6%), CD44v8-10 high expression in 87 (63.5%) and Nestin high expression in 21 (16.1%). Multivariate survival analysis found that high-positive OV IgG and late stage tumor were independent prognostic factors with the adjusted HR of 2.24 (95% CI 1.27–3.93) and 2.78 (95% CI 1.46–5.29), respectively. Subgroup analysis in early and late stage CCA showed that a combined positive OV IgG and CD44s expression with the high expression of CD44v8-10 had the significantly poorest prognosis with HR of 3.75 (95% CI 1.61–8.72) and HR of 1.76 (95% CI 1.02–3.03), respectively.ConclusionA high level of OV IgG as well as a high level of CSC markers resulted in an aggressive CCA. OV IgG level together with CSC markers can be used as the prognostic markers for CCA patients’ survival. The study of the CD44 pathway is promising for adjuvant treatment.