Discrimination, cognitive styles, and their associations with adolescents' mental and physical health.

This study is based on the hopelessness theory of depression and previous research on perceived everyday discrimination (PED) and both depressive symptoms and Interleukin-6 (an inflammatory cytokine; IL-6) in adolescents. The purpose of this study is to examine the negative attribution, self, and consequence cognitive styles (CSs) proposed in the hopelessness theory as a possible mechanism underlying the association between PED and inflammation in adolescents and expand our understanding of the comorbidities between depressive symptoms and systemic inflammation (IL-6). This cross-sectional study featured a sample of 102 adolescents aged 13-16 (M = 14.10, SD = 0.52) who identified as White (47.5%), Black (41.4%), Mixed Race (7.1%), Latino (2%), and other (2%). Data analysis was conducted using PROCESS to compute regressions and effects between PED, negative CSs, depressive symptoms, and Interleukin-6. Results showed that negative attribution CS is the only negative CS associated with PED, depressive symptoms, and IL-6. Negative attribution CS is also the only negative CS of the three negative CSs that mediates both the association between PED and depressive symptoms and PED and IL-6 in our adolescent sample. Overall, these results indicate that individual negative CSs proposed in the hopelessness theory impact adolescents' physical and mental outcomes differently, which can inform targeted treatments. Nurses should provide cognitive-based interventions and promote societal-level change to reduce the experience and impact of PED on the mental and physical health of their adolescent patients.

Conformational state of C-reactive protein is critical for reducing immune complex-triggered type I interferon response: Implications for pathogenic mechanisms in autoimmune diseases imprinted by type I interferon gene dysregulation.

Presence of autoantibodies targeting nuclear constituents, i.e., double-stranded DNA and small nuclear ribonucleoproteins (snRNPs), remain a cornerstone in systemic lupus erythematosus (SLE). Fcγ receptor IIa (FcγRIIa) dependent uptake of nucleic acid containing immune complexes (ICs) by plasmacytoid dendritic cells (PDCs) can activate toll-like receptors (TLRs) such as TLR7 and TLR9 resulting in type I interferon (IFN) production. Previously, the classical liver-derived acute-phase reactant C-reactive protein (CRP) has been suggested to reduce IC-induced type I IFN production, whereas monomeric (mCRP) vs. pentameric (pCRP) mediated effects have not yet been unraveled. Herein, peripheral blood mononuclear cells (PBMCs) or enriched blood DCs from healthy volunteers were stimulated with SLE sera, snRNP-IgG (ICs), or TLR ligands with or without pCRP, mCRP, or anti-FcγRIIa antibody. Type I IFNs and cytokine responses were investigated using quantitative PCR, ELISA, and flow cytometry. pCRP inhibited IFN gene expression in PBMCs and enriched DCs after incubation with ICs, compared to ICs alone, whereas mCRP had significantly less inhibitory effect. The effect was independent on the order in which IC or CRP was added to the cells. In addition, pCRP inhibited IFN induced by other TLR stimulators, implicating broader inhibitory effects induced by pCRP. We demonstrate pronounced immunoregulatory functions of CRP whereas the inhibitory properties were evidently dependent on CRP's intact conformational state. The inhibition of type I IFNs was not due to competition of FcγRs, or binding of CRP to the ICs. Our findings have implications for autoimmune IC-mediated conditions imprinted by type I IFN gene dysregulation.

Extracellular vesicles opsonized by monomeric C-reactive protein (CRP) are accessible as autoantigens in patients with systemic lupus erythematosus and associate with autoantibodies against CRP.

The pentraxin C-reactive protein (CRP) is a pentameric protein now known to be able to undergo dissociation into a monomeric, modified isoform, referred to as mCRP. In carefully assessing the bioactivities of each isoform, mCRP has strong pro-inflammatory activities while pCRP has mild anti-inflammatory activities. Systemic lupus erythematosus (SLE) is a disease characterized by a vast number of autoantibodies, including anti-CRP autoantibodies which have been associated with SLE disease activity and lupus nephritis. The origin of these autoantibodies is currently unknown. Extracellular vesicles (EVs) have been implicated in SLE pathogenesis as they can expose nuclear antigens on their outside surface, thereby being a potential adjuvant for the generation of autoantibodies. Herein, we studied exposure of both pCRP and mCRP on EVs in SLE plasma and the implications of each in disease activity, organ damage and clinical manifestations. We used flow cytometry to detect CRP isoforms on EV surfaces in 67 well-characterized SLE patients and 60 sex- and age-matched healthy controls. Autoantibodies against mCRP were measured using ELISA. We found an abundance of both pCRP and mCRP on SLE EVs compared to controls. Furthermore, mCRP+ but not pCRP+ EVs were elevated in patients with active disease and in anti-CRP positive patients. The proportions of mCRP+ EVs were lower in patients with acquired organ damage, especially in patients with lupus nephritis (LN), and displayed an inverse relationship with disease duration in LN and patients with active disease. Speculatively, these data suggest EV-bound mCRP as a relevant factor in SLE pathogenesis, which could contribute to development of anti-CRP autoantibodies by stimulating an immune response.

Association and predictive value of biomarkers with severe outcomes in hospitalized patients with SARS-CoV-2 infection.

This study analyzed the levels at admission of biomarkers for their association with and ability to predict risk of severe outcomes, including admission to the ICU, need for invasive mechanical ventilation (IMV), need for vasopressor use (VU), and in-hospital mortality (IHM) in 700 patients hospitalized with COVID-19. Biomarker data split by outcomes was compared using Mann-Whitney U tests; frequencies of biomarker values were compared using Chi-square tests and multivariable logistic regression analysis was performed to look at the impact of biomarkers by outcome. Patients that suffered IHM were more likely to have reduced platelet numbers and high blood urea nitrogen (BUN) levels among patients admitted to the ICU. Risk factors for mortality were related to hyper-coagulability (low platelet count and increased D-dimer) and decreased respiratory (PaO2/FiO2 ratio) and kidney function (BUN). Association with risks of other severe outcomes were as follows: ICU with hyper-inflammation (IL-6) and decreased respiratory function; IMV with low platelet count, abnormal neutrophil-lymphocyte ratio with reduced respiratory function, VU with inflammatory markers (IL-6), and low platelet count with respiratory function. Our studies confirmed the association of biomarkers of hematological, inflammatory, coagulation, pulmonary and kidney functions with disease severity. Whether these biomarkers have any mechanistic or causal role in the disease progress requires further investigation.

Changes in liver steatosis in HIV-positive women are associated with the BMI, but not with biomarkers.

The prevalence of non-alcoholic fatty liver disease (NAFLD) is higher in HIV-infected patients compared to the general population. While metabolic risk factors such as obesity, insulin resistance and the metabolic syndrome have been identified as key risk factors in all individuals, there is limited information regarding the mechanisms that contribute to the higher prevalence among individuals living with HIV, particularly among women and ethnic minorities. The aim of this study was to determine the association, over two time points, of a panel of biomarkers with liver steatosis in a cohort of HIV-seropositive women and age-matched negative controls and to investigate whether the association differed by HIV status. To this effect, plasma samples obtained from 105 HIV-positive and -negative participants enrolled in the Women's Interagency HIV study (WIHS) Washington DC site were assayed for biomarkers associated with inflammation, adipose tissue function, fibrinolysis, gut permeability and hepatocyte apoptosis/necrosis. Their association with liver steatosis, measured using Controlled-Attenuation Parameter (CAP) scores determined by transient elastography, were then analyzed. HIV positivity was associated with lower median IL-17A and higher IL-22 and sCD14 values. There were no statistically significant associations between HIV status, biomarkers or covariates with CAP measurement over two time points. However, IL-1ß levels were associated with higher CAP scores at the second visit. Across all statistical models, an increase in BMI was associated with an increase in CAP measurements. No statistically significant associations were found between viral load history, CD4 + T-cell count, biomarkers and covariates, including ART use, on CAP measurements. These results confirm that BMI is a key risk factor for liver steatosis independent of HIV status. The potential contributions to NAFLD of differences in IL-1ß, Th17-family cytokines and gut permeability between HIV-positive vs. negative individuals require further study.

The elevated systemic cytokine levels in HIV patients are not associated with an elevated pulmonary cytokine environment.

BACKGROUND: HIV-positive patients on anti-retroviral therapy (ART) are at higher risk of developing many non-AIDS related chronic diseases, including chronic obstructive pulmonary disease (COPD), compared to HIV-negative individuals. While the mechanisms are not clear, a persistent pro-inflammatory state appears to be a key contributing factor. The aims of this study were to investigate whether HIV-positive patients without COPD present evidence of potentially predisposing abnormal pulmonary cytokine/chemokine environment and to explore the relationship between pulmonary and systemic cytokine levels. METHODS: This study included 39 HIV-seropositive and 34 HIV-seronegative subjects without COPD. All were subjected to outpatient bronchoscopy with bronchoalveolar lavage fluid (BALF) aspiration and blood sample collection. The levels of 21 cytokines and chemokines were measured in plasma and BALF using a bead-based multi-analyte assay. RESULTS: In plasma, HIV-infected patients showed significantly increased circulating levels of pro-inflammatory (TNFα) and Th1-associated cytokines (IL-12p70) as well as several chemokines (CXCL11 and CX3CL1). However, no statistically significant differences were found in the numbers of cells, the concentrations of protein and urea as well as cytokine levels in the BALFs of HIV-positive patients when compared to controls. Correlation analysis indicated a potential modulatory effect of the BMI in HIV-seropositive individuals. CONCLUSIONS: While our results are consistent with the existence of a systemic pro-inflammatory state in HIV-infected patients, they did not detect significant differences in cytokine levels and other inflammatory markers in the lungs of HIV-positive individuals when compared to HIV-negative controls.

Adults Hospitalized With Pneumonia in the United States: Incidence, Epidemiology, and Mortality.

BACKGROUND: Understanding the burden of community-acquired pneumonia (CAP) is critical to allocate resources for prevention, management, and research. The objectives of this study were to define incidence, epidemiology, and mortality of adult patients hospitalized with CAP in the city of Louisville, and to estimate burden of CAP in the US adult population. METHODS: This was a prospective population-based cohort study of adult residents in Louisville, Kentucky, from 1 June 2014 to 31 May 2016. Consecutive hospitalized patients with CAP were enrolled at all adult hospitals in Louisville. The annual population-based CAP incidence was calculated. Geospatial epidemiology was used to define ecological associations among CAP and income level, race, and age. Mortality was evaluated during hospitalization and at 30 days, 6 months, and 1 year after hospitalization. RESULTS: During the 2-year study, from a Louisville population of 587499 adults, 186384 hospitalizations occurred. A total of 7449 unique patients hospitalized with CAP were documented. The annual age-adjusted incidence was 649 patients hospitalized with CAP per 100000 adults (95% confidence interval, 628.2-669.8), corresponding to 1591825 annual adult CAP hospitalizations in the United States. Clusters of CAP cases were found in areas with low-income and black/African American populations. Mortality during hospitalization was 6.5%, corresponding to 102821 annual deaths in the United States. Mortality at 30 days, 6 months, and 1 year was 13.0%, 23.4%, and 30.6%, respectively. CONCLUSIONS: The estimated US burden of CAP is substantial, with >1.5 million unique adults being hospitalized annually, 100000 deaths occurring during hospitalization, and approximately 1 of 3 patients hospitalized with CAP dying within 1 year.

Acute stress induces increases in salivary IL-10 levels.

The purpose of this study was to investigate the stress-reactivity of the anti-inflammatory cytokine, IL-10, in saliva and to determine how salivary IL-10 levels change in relation to those of IL-1ß, a pro-inflammatory cytokine, following stress. Healthy young adults were randomly assigned to retrieve a negative emotional memory (n = 46) or complete a modified version of the Trier Social Stress Test (n = 45). Saliva samples were taken 10 min before (baseline) and 50 min after (post-stressor) onset of a 10-min stressor, and were assayed using a high sensitivity multiplex assay for cytokines. Measurable IL-10 levels (above the minimum detectable concentration) were found in 96% of the baseline samples, and 98% of the post-stressor samples. Flow rate-adjusted salivary IL-10 levels as well as IL-1ß/IL-10 ratios showed moderate but statistically significant increases in response to stress. Measurement of salivary IL-10 and pro-/anti-inflammatory cytokine ratios may be useful, noninvasive tools, in stress research.

Macrolide Use and Neutrophil Function/Cytokine Levels in Hospitalized Patients with Community-Acquired Pneumonia: A Pilot Study.

PURPOSE: The objective of this study was to measure plasma cytokine levels and blood neutrophil functions as well as clinical outcomes in hospitalized patients with community-acquired pneumonia (CAP) treated with or without macrolide use--a known modulator of inflammatory response. METHODS: Subjects with CAP had peripheral blood analyzed for some neutrophil functions (degranulation of secretory vesicles and specific granules, respiratory burst response and phagocytosis) and ten cytokine levels measured in serum and sputum supernatants. Neutrophil function in healthy volunteers was also measured for reference. Values were measured on the day of enrollment, days 2-4 and 5-7, depending on a patient's length of stay. Early and late clinical outcomes were also evaluated. All values were compared between those treated with or without a macrolide. RESULTS: A total of 40 subjects were in this study; 14 received macrolide treatment, and 26 did not. Neutrophil function in the macrolide group was not significantly different compared to the non-macrolide group. None of the median cytokine levels or IQRs were statistically significant between the groups. However, a trend toward decreased IL-6, IL-8, and IFN-γ levels, and favorable clinical outcomes were present in the macrolide group. CONCLUSIONS: This pilot study showed no statistical difference between cytokine levels or neutrophil activity for CAP patients prescribed a macrolide containing regimen. Considering the trend of lower cytokine levels in the macrolide group when comparing the 5- to 7-day time period with the non-macrolide group, a full study with an appropriate sample size may be warranted.

Synthesis and evaluation of 1,5-dithialaminaribiose and -triose tetravalent constructs.

We report the synthesis of novel tetravalent glucoclusters containing 1,5-dithia mimetics of laminaribiose and triose. The new constructs were evaluated for their ability to inhibit anti-CR3 fluorescent staining of human neutrophils, for which they showed moderate affinity. Evaluation of the synthesized glycoclusters for their ability to inhibit anti-Dectin-1 fluorescent staining of mouse macrophages revealed little to no affinity for Dectin-1.

Pentameric C-reactive protein is a better prognostic biomarker and remains elevated for longer than monomeric CRP in hospitalized patients with COVID-19.

The differing roles of the pentameric (p) and monomeric (m) C-reactive protein (CRP) isoforms in viral diseases are not fully understood, which was apparent during the COVID-19 pandemic regarding the clinical course of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Herein, we investigated the predictive value of the pCRP and mCRP isoforms for COVID-19 severity in hospitalized patients and evaluated how the levels of the protein isoforms changed over time during and after acute illness. This study utilized samples from a well-characterized cohort of Swedish patients with SARS-CoV-2 infection, the majority of whom had known risk factors for severe COVID-19 and required hospitalization. The levels of pCRP were significantly raised in patients with severe COVID-19 and in contrast to mCRP the levels were significantly associated with disease severity. Additionally, the pCRP levels remained elevated for at least six weeks post inclusion, which was longer compared to the two weeks for mCRP. Our data indicates a low level of inflammation lasting for at least six weeks following COVID-19, which might indicate that the disease has an adverse effect on the immune system even after the viral infection is resolved. It is also clear that the current standard method of testing pCRP levels upon hospitalization is a useful marker for predicting disease severity and mCRP testing would not add any clinical relevance for patients with COVID-19.

Epidemiology of Pneumococcal Pneumonia in Louisville, Kentucky, and Its Estimated Burden of Disease in the United States.

Streptococcus pneumoniae remains a primary pathogen in hospitalized patients with community-acquired pneumonia (CAP). The objective of this study was to define the epidemiology of pneumococcal pneumonia in Louisville, Kentucky, and to estimate the burden of pneumococcal pneumonia in the United States (US). This study was nested in a prospective population-based cohort study of all adult residents in Louisville, Kentucky, who were hospitalized with CAP from 1 June 2014 to 31 May 2016. In hospitalized patients with CAP, urinary antigen detection of 24 S. pneumoniae serotypes (UAD-24) was performed. The annual population-based pneumococcal pneumonia incidence was calculated. The distribution of S. pneumoniae serotypes was characterized. Ecological associations between pneumococcal pneumonia and income level, race, and age were defined. Mortality was evaluated during hospitalization and at 30 days, 6 months, and 1 year after hospitalization. Among the 5402 CAP patients with a UAD-24 test performed, 708 (13%) patients had pneumococcal pneumonia. The annual cumulative incidence was 93 pneumococcal pneumonia hospitalizations per 100,000 adults (95% CI = 91-95), corresponding to an estimated 226,696 annual pneumococcal pneumonia hospitalizations in the US. The most frequent serotypes were 19A (12%), 3 (11%), and 22F (11%). Clusters of cases were found in areas with low incomes and a higher proportion of Black or African American population. Pneumococcal pneumonia mortality was 3.7% during hospitalization, 8.2% at 30 days, 17.6% at 6 months, and 25.4% at 1 year after hospitalization. The burden of pneumococcal pneumonia in the US remains significant, with an estimate of more than 225,000 adults hospitalized annually, and approximately 1 out of 4 hospitalized adult patients dies within 1 year after hospitalization.

Associations of C-reactive protein isoforms with systemic lupus erythematosus phenotypes and disease activity.

BACKGROUND: Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by a large production of autoantibodies and deficient clearance of cellular waste. The disease typically oscillates between episodes of elevated disease activity and quiescent disease. C-reactive protein (CRP) is a pentameric acute-phase protein usually reflecting inflammation and tissue damage. However, despite increased inflammation and elevated interleukin-6, the levels of CRP typically remain low or only slightly raised in SLE. Under certain conditions, pentameric CRP (pCRP) can dissociate into its monomeric isoform (mCRP), which mainly has been ascribed pro-inflammatory properties. The present study aims to investigate the potential relationship between pCRP and mCRP, respectively, with disease activity and clinical features of SLE. METHODS: The levels of pCRP and mCRP were measured, by turbidimetry (high-sensitive) and sandwich enzyme-linked immunosorbent assay (ELISA) respectively, in serum samples from 160 patients with SLE and 30 patients with antineutrophil cytoplasmic antibody-associated vasculitis (AAV). Twenty-two of the SLE cases were selected for analysis at two time-points; quiescent disease and active disease. The two CRP isoforms were evaluated in relation to disease activity and clinical features in the two diseases. RESULTS: Levels of pCRP and mCRP were significantly lower in SLE than AAV (p < 0.001) and the ratio of mCRP/pCRP was higher in SLE compared to AAV. The mCRP/pCRP ratio was higher for patients in remission and able to significantly separate between active/quiescent disease in paired, but not in non-paired, samples from patients with SLE. Significant correlations were observed with SLICC/ACR damage index for pCRP levels as well as inversely with the mCRP/pCRP ratio. Lower mCRP levels associated with malar rash. CONCLUSION: As the interrelationship between the two isoforms appear to (a) discriminate between quiescent and active SLE and (b) differ between SLE and AAV, our data indicates that the two CRP isoforms could exert contrasting immunological effects and/or reflect different milieus. Given the biological effects of mCRP, it is possible that altered levels may indicate increased opsonization of immune complexes and apoptotic debris, and thereby prevent their deposition outside the reticuloendothelial system and manifestations such as lupus nephritis and lupus-related skin disease.

Lower levels of interleukin-12 precede the development of tuberculosis among HIV-infected women.

Tuberculosis (TB) is the worldwide leading cause of death among HIV-infected individuals, accounting for more than half of AIDS-related deaths. A high risk of tuberculosis (TB) has been shown in early stages of the HIV disease, even in the presence of normal CD4(+) cell counts. Moreover, the factors that determine protective immunity vs. susceptibility to Mycobacterium tuberculosis cannot be fully explained by simple changes in IFNγ levels or a shift from Th1 to Th2 cytokines. This work investigated the relationship between cytokine expression profiles in peripheral blood mononuclear cells (PBMC) and susceptibility to M. tuberculosis in 10 HIV+ women who went onto develop TB. RNA transcripts for IL-4, IL-4δ2, IL-10, IL-12(p35), IL-13, IL-17A, IFNγ and TNFα were measured by real-time quantitative PCR in unstimulated or TB peptide antigen-stimulated PBMCs from 10 HIV+ women with positive tuberculin skin tests (TST) and compared with HIV-seropositive and seronegative women without previous TB and negative TST. Stimulated PBMC cultures showed significantly lower expression of IL-12p35 (p=0.004) and IL-10 (p=0.026) in the HIV+TB+ group 6-12months before onset of TB compared to HIV+TB- women. Unstimulated PBMC from HIV+TB+ women also had lower expression of Th2 cytokines [IL-4 (p=0.056) and IL-13 (p=0.050)] compared to HIV+TB- women. These results suggest that lower IL-12 production by PBMC in response to TB antigens and lower levels of both Th1 and Th2 cytokines by PBMC correlate with future development of TB in HIV-infected women and may be responsible for their increased susceptibility.

Correlations among inflammatory markers in plasma, saliva and oral mucosal transudate in post-menopausal women with past intimate partner violence.

The relationship between psychosocial factors and an increased risk for disease has been related to a heightened pro-inflammatory status reflected in increased circulating levels of pro-inflammatory cytokines and/or C-reactive protein (CRP). Routinely, epidemiological studies rely on measurements of inflammatory markers in serum or plasma, but the use of biological fluids such as saliva or oral mucosal transudate (OMT) may offer potential advantages. This study investigated correlations among plasma CRP and levels of IL-6 and soluble IL-6 receptor (sIL-6R) in plasma, saliva and OMT in a population of middle aged women with histories of past intimate partner violence (IPV). A total of 67 women without existing chronic diseases participated in the study, which included two visits each in which psychological tests were administered, and blood, saliva and OMT samples were collected. Although significantly higher plasma CRP levels were found in past IPV sufferers compared to controls, there were no significant differences in IL-6 or sIL-6R levels in plasma, saliva or OMT between the two groups. There were only relatively modest correlations between IL-6 levels in plasma and those in saliva or OMT and between plasma IL-6 and CRP levels. A significant correlation between IL-6 and sIL-6R levels in both saliva and OMT, but not in plasma, was also detected. No significant correlations were found between levels of IL-6 in saliva or OMT and periodontal health measures. Results indicate that IL-6 and sIL-6R levels in saliva or OMT do not closely reflect those in plasma, and therefore are not a good surrogate for systemic levels.

The levels of soluble urokinase plasminogen activator receptor (suPAR) in saliva are influenced by acute stress.

Although elevations in systemic suPAR levels have been associated with inflammatory conditions and with exposure to life stress and adversity, it is not yet clear whether acute psychological stress influences suPAR levels, either systemically and/or in saliva. The aim of this study was to investigate whether salivary suPAR levels are increased following exposure to acute psychological stress. Healthy subjects, aged 18-40 years, completed a laboratory psychological stressor and provided saliva samples before and after the stress test (60 min apart). Levels of suPAR as well as those of cytokines increased in the post-stress samples (all ps < .001). Baseline and post-stress IL-1ß and TNF-α as well as post-stress IL-6 correlated significantly with suPAR (all ps < .01), but IL-10 and baseline IL-6 did not. These results show that suPAR levels in saliva are stress-reactive and suggest a potential application as stress biomarkers in saliva, particularly given the advantage of easily detectable concentrations.

Insights into the Use of C-Reactive Protein as a Diagnostic Index of Disease Severity in COVID-19 Infections.

Approximately 20% of patients infected with SARS-CoV-2 (COVID-19) develop potentially life-threatening pathologies involving hyperinflammation, cytokine storm, septic shock complications, coagulation dysfunction, and multiple organ failure. Blood levels of the prototypic acute phase reactant, C-reactive protein (CRP), which is hepatically synthesized and released in response to interleukin-6 stimulation, is markedly elevated in patients with COVID-19. Markedly high CRP levels correlate with poor prognosis for survival. Insights into CRP structure-function relationships have uncovered both pro- and anti-inflammatory isoforms that may be used to monitor the extent of tissue damage associated with COVID-19 pathologies and prognoses. Herein, rationale is given for interpretation of CRP blood levels as a simple, rapid, and cost-effective way to assess disease severity and help guide therapeutic options in COVID-19 patients.

Seroprevalence of Helicobacter pylori/CagA Antibodies in Guatemalan Gastric Cancer Patients: Association of Seropositivity with Increased Plasma Levels of Pepsinogens but not Soluble Urokinase Plasminogen Activator Receptor.

Infection by Helicobacter pylori is a major risk factor for gastric cancer (GC), the second leading cause of cancer-related death worldwide. Although biomarkers such as pepsinogens (PGs) and soluble urokinase plasminogen activator receptor (suPAR) may have diagnostic and/or prognostic value in patients with GC, their levels may be affected by H. pylori infection. The aim of this study was to investigate the association of the presence of antibodies to H. pylori and cytotoxin-associated gene A (CagA) with plasma levels of PGs and suPAR in a cohort of Guatemalan GC patients and controls. To this end, levels of suPAR, Pepsinogens I and II (PGI and PGII), and antibodies to H. pylori and CagA toxin were determined by ELISA in plasma samples from 67 GC patients and 136 matched healthy controls. Seropositivity for CagA was significantly higher in patients with GC than in controls. Pepsinogens II and suPAR levels were higher and PGI/PGII ratios were lower in GC patients than in controls. There was a significant association of H. pylori seropositivity status with increased levels of PGII and lower PGI/PGII ratios, particularly in the control (non-GC) population. The levels of suPAR were not significantly affected by H. pylori or CagA seropositivity status. These results suggest that the seropositivity status for H. pylori and CagA need to be taken into account during the GC diagnostic process.

Cumulative trauma, emotion reactivity and salivary cytokine levels following acute stress in healthy women.

BACKGROUND AND OBJECTIVES: To better understand how trauma leads to poor health, this study examined whether cumulative trauma and emotion reactivity contribute to pro- (IL-1ß) and anti-inflammatory (IL-10) salivary cytokine levels after stress. DESIGN: Seventy-three women, screened to be physically and mentally healthy, completed an acute stress paradigm and measures of lifetime trauma exposure. METHOD: Saliva was collected 10 min before (i.e., baseline) and 35 min after the onset of a 10-min stressor. State negative and positive emotion were measured at baseline and post-stress. RESULTS: Most participants reported exposure to at least one trauma, with a mean of five. Cumulative trauma was associated with higher post-stress IL-1ß and IL-1ß/IL-10, but not with IL-10 or changes in emotion. Declines in positive emotion correlated with greater post-stress IL-1ß. CONCLUSIONS: These findings suggest that both cumulative trauma exposure and positive emotion have implications for salivary cytokine responses to acute stress. The inclusion of healthy women strengthens internal validity, and increases confidence that observed associations between trauma and salivary cytokine responses can be attributed to trauma, rather than to confounding health problems. This study adds to the growing literature examining how trauma may connect to cytokines, and ultimately, poor health.

Cell-free DNA diagnostics: current and emerging applications in oncology.

Liquid biopsy is a noninvasive dynamic approach for monitoring disease over time. It offers advantages including limited risks of blood sampling, opportunity for more frequent sampling, lower costs and theoretically non-biased sampling compared with tissue biopsy. There is a high degree of concordance between circulating tumor DNA mutations versus primary tumor mutations. Remote sampling of circulating tumor DNA can serve as viable option in clinical diagnostics. Here, we discuss the progress toward broad adoption of liquid biopsy as a diagnostic tool and discuss knowledge gaps that remain to be addressed.