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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

Perfil de citocinas Th1, Th2, Th17 y otras citocinas pro inflamatorias (IL-1ß, IL-6 y TNFα) en el plasma de pacientes con cáncer gástrico / Th1, Th2, Th17 cytokine profile and other pro-inflammatory cytokines (IL-1ß, IL-6 and TNFα) in the plasma of patients with gastric cancer

El cáncer gástrico (CG) es la neoplasia del tubo digestivo más prevalente en el mundo, asociada a factores genéticos del hospedero y externos, como infección por Helicobacter pylori. La patogénesis incluye inflamación crónica mediada por citocinas del microambiente tumoral, detectables sistémicamente. Estudios previos reportan niveles séricos de citocinas y su contribución al diagnóstico de CG. El presente estudio analiza el perfil de citocinas del tipo de Th1(IFNγ), Th2(IL-4 e IL-10), Th17(Th-17A) y otras pro inflamatorias: IL-1ß, IL-6 y TNF-α, en plasma de 70 casos de pacientes con CG comparándolos con 132 sujetos sanos equiparables en edad y sexo. Los casos provinieron del Hospital Roosevelt e Instituto Nacional de Cancerología de Guatemala (Incan) y formaron parte de un estudio previo. Se analizó la base de datos clínicos, patológicos y epidemiológicos. Se midieron los niveles de citocinas utilizando el sistema "MSD MULTI-SPOT Assay System". La edad promedio de los casos fue 59.5 años, (DE 13.0), 51%, eran positivos para IgG anti H. pylori. Un 71% presentó adenocarcinoma grado III (Borrman), según clasificación de Lauren 55% tenían tipo intestinal. Las siete citocinas cuantificadas se encontraron significativamente elevadas (p < .05) en el plasma de los casos respecto a sus controles. Los casos de CG tipo difuso presentaron niveles de IFNγ significativa-mente elevados. Por regresión logística, las citocinas IL-6 e IL-10, están asociadas significativamente a CG (p < .05) independientemente del estatus de infección por H. pylori. Se destacan la IL-6 e IL-10 como las principales citocinas asociadas a la presencia de CG.

Gastric cancer (GC) is the most prevalent gastrointestinal neoplasm in the world, associated with host and external genetic factors, such as Helicobacter pylori infection. The pathogenesis includes chronic inflammation mediated by cytokines of the tumor microenvironment, systemically detectable. Previous studies report serum levels of cyto-kines and their contribution to the diagnosis of GC. The present study analyzes the profile of cytokines of the type Th1 (IFNγ), Th2 (IL-4 and IL-10), Th17 (Th-17A) and other pro-inflammatory: IL-1ß, IL-6 and TNF-α, in plasma of 70 cases of patients with GC compared with 132 healthy subjects comparable in age and sex. The cases came from the Roosevelt Hospital and the National Cancer Institute of Guatemala -Incan- and were part of a previous study. The clinical, pathological and epidemiological databases were analyzed. Cytokine levels were measured using the "MSD MULTI-SPOT Assay System". The average age of the cases was 59.5 years, (SD 13.0), 51% were positive for IgG anti H. pylori, 71% had grade III adenocarcinoma (Borrman), according to Laurenís classification, 55% had intestinal type. The seven cytokines quantified were found to be significantly elevated (p < .05) in the plasma of the cases compared to their controls. The diffuse GC cases presented significantly elevated IFNγ levels. By logistic regression, the cytokines IL-6 and IL-10 are significantly associated with GC (p < .05) regardless of the H. pylori infection status. IL-6 and IL-10 stand out as the main cytokines associated with the presence of GC.

Asociación del grupo sanguíneo ABO con susceptibilidad a COVID-19 / Association of ABO blood group with COVID-19 susceptibility

La pandemia de COVID-19, causada por el virus SARS-CoV-2, ha infectado ya a más de 25 millones de personas, ocasionando más de 850,000 muertos y causando serios problemas en hospitales y sistemas de salud en todo el mundo. Una de las mayores dificultades que presenta la infección por SARS-CoV-2 es su gran variación en presentación clínica, que puede ir desde casos asintomáticos hasta síndromes de distrés respiratorio agudo, fallo múltiple de órganos y muerte. De aquí la importancia del estudio de factores demográficos, clínicos y genéticos que permitan la identificación de personas con mayor riesgo de adquirir la infección y sufrir manifestaciones graves de la enfermedad. Un número creciente de reportes en la literatura han sugerido que el grupo sanguíneo ABO está relacionado con el riesgo a COVID-19, coincidiendo en que personas con sangre del grupo A muestran el mayor riesgo, mientras que personas con sangre del grupo O el menor. Los objetivos de esta revisión son presentar un resumen de la evidencia existente en la literatura científica reciente y discutir estas observaciones en el contexto del conocimiento sobre la asociación de los grupos sanguíneos a varias infecciones y otras enfermedades, así como de los mecanismos potenciales involucrados. Finalmente, las implicaciones de la relación entre el grupo sanguíneo y susceptibilidad a COVID-19 son también discutidas con relación a la población guatemalteca.

The COVID-19 pandemic, caused by the SARS-CoV-2 virus, has already infected more than 25 million people, resulting in more than 850,000 deaths and causing serious problems in hospitals and health systems worldwide. One of the biggest problems posed by the SARS-CoV-2 infection is its great variation in clinical presentation, which can range from asymptomatic cases to syndromes of acute respiratory distress, multiple organ failure, and death. Hence the importance of studying demographic, clinical and genetic factors that allow the identification of people at increased risk of suffering serious manifestations. A growing number of reports in the literature have suggested that the ABO blood group is related to the risk of COVID-19, demonstrating that people with type A blood have the highest risk, while people with type O blood the lowest. The objective of this review is to present a summary of the existing evidence in the recent scientific literature and to discuss these observations in the context of the knowledge of the association of blood groups to various infections and other diseases, as well as the potential mechanisms involved. Finally, the implications of the relationship between the blood groups and COVID-19 susceptibility are also discussed in relationship to the Guatemalan population.

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.

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.

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.

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.

The order of administration of macrolides and beta-lactams may impact the outcomes of hospitalized patients with community-acquired pneumonia: results from the community-acquired pneumonia organization.

BACKGROUND: The beneficial effect of macrolides for the treatment of community-acquired pneumonia (CAP) in combination with beta-lactams may be due to their anti-inflammatory activity. In patients with pneumococcal meningitis, the use of steroids improves outcomes only if they are administered before beta-lactams. The objective of this study was to compare outcomes in hospitalized patients with CAP when macrolides were administered before, simultaneously with, or after beta-lactams. METHODS: Secondary data analysis of the Community-Acquired Pneumonia Organization (CAPO) International Cohort Study database. Study groups were defined based on the sequence of administration of macrolides and beta-lactams. The study outcomes were time to clinical stability (TCS), length of stay (LOS) and in-hospital mortality. Accelerated failure time models were used to evaluate the adjusted impact of sequential antibiotic administration and time-to-event outcomes, while a logistic regression model was used to evaluate their adjusted impact on mortality. RESULTS: A total of 99 patients were included in the macrolide before group and 305 in the macrolide after group. Administration of a macrolide before a beta-lactam compared to after a beta-lactam reduced TCS (3 vs. 4 days, p = .011), LOS (6 vs. 7 days, p = .002) and mortality (3 vs. 7.2%, p = .228). CONCLUSIONS: The administration of macrolides before beta-lactams was associated with a statistically significant decrease in TCS and LOS and a non-statistically significant decrease in mortality. The beneficial effect of macrolides in hospitalized patient with CAP may occur only if administered before beta-lactams.

Valor diagnóstico de las proteínas uPAR en sangre para el cáncer gástrico en Guatemala / Diagnostic value of blood uPAR proteins for gastric cancer in Guatemala

El cáncer gástrico es la neoplasia más frecuente del tubo digestivo, Guatemala posee altas tasas de incidencia y mortalidad. Helicobacter pylori se ha identificado como un carcinógeno gástrico, especialmente si la infección es por cepas que expresen factor de virulencia CagA, asociado a lesiones atróficas y precancerosas. Reportes previos indican que el análisis de biopsias gástricas en pacientes positivos para H. pylori, muestran un incremento de la expresión del activador del plasminógeno uroquinasa (uPA) y su receptor (uPAR). El presente estudio tuvo como objetivo determinar el valor diagnóstico de uPAR en sangre como marcador de cáncer gástrico en Guatemala y la asociación de uPAR con la infección por de H. pylori. Se tomaron muestras sanguíneas de pacientes diagnosticados con cáncer gástrico (n = 68) y controles sanos apareados por edad y sexo (n = 136) en cuatro instituciones de la ciudad de Guatemala, se determinó uPAR e IgG anti H. pylori por metodología Elisa. Los niveles de uPAR en pacientes con cáncer estaban significativamente elevados (p < .001), no se encontró diferencia por edad, sexo, apariencia macroscópica o microscópica del tumor. El cáncer gástrico se asoció significativamente a H. pylori (p = .03). El coeficiente de correlación biserial indica una relación negativa débil (rb = -0.01, p = .443) entre uPAR y H. pylori. Las curvas ROC en uPAR reportaron alta precisión (área bajo la curva = .80) para identificar cáncer gástrico. Estos resultados sugieren que los niveles séricos de uPAR pueden tener valor en el diagnóstico cáncer gástrico.

Gastric cancer is the most frequent neoplasm of the digestive tract, Guatemala has high incidence and mortality rates. Helicobacter pylori has been identified as a gastric carcinogen, especially if the infection is by strains expressing virulence factor CagA which is associated with atrophic and precancerous lesions. Previous reports indicate that gastric biopsy analyses in H. pylori positive patients show increased expression of urokinase plasminogen activator (uPA) and its receptor (uPAR). The present study aimed to determine the diagnostic value of uPAR in blood as a marker of gastric cancer in Guatemala and the association of uPAR with infection by of H. pylori. Blood samples were collected from patients diagnosed with gastric cancer (n = 68) and healthy controls matched by age and sex (n = 136) at four institutions in Guatemala City and analyzed for uPAR and anti-H. pylori IgG. uPAR levels in cancer patients were found to be significantly elevated (p <.001), but were not influenced by age, sex, macroscopic or microscopic appearance of the tumor. Gastric cancer was significantly associated with H. pylori (p = .03). The serial correlation analysis used to determine the correlation of uPAR with H. pylori showed that there is a non-significant weak negative Pearson's correlation coefficient (r = -0.01, p = .443) between both. The ROC curves for uPAR indicated high precision (AUC = 0.80) for detection of gastric cancer. These results suggest that serum uPAR levels may be valuable in the diagnosis of gastric cancer.

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.