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Purpose. We examined the effect of cancer caregiver stress and negative attribution style (NAS) on depressive symptoms and salivary cortisol. Method. The sample came from a hospital bone marrow unit and caregiver support organizations and included 60 informal cancer caregivers (51.7% partners) of cancer patients (provided care for a median of 27.5 hours per week for 12 months) and 46 non-caregiver participants. In this cross-sectional study, participants completed questionnaires assessing NAS and depressive symptoms and provided saliva samples to measure cortisol. Results. Linear regressions demonstrated that cancer caregiver stress (p=0.001) and the cancer caregiver stress by NAS interaction (p=0.017), but not NAS alone (p=0.152), predicted depressive symptoms. Caregivers independent of their NAS and non-caregivers high in NAS reported high depression while non-caregivers low in NAS reported low depression. Neither cancer caregiver stress (p=0.920) nor NAS alone (p=0.114), but their interaction, predicted cortisol (p=0.036). Higher NAS was associated with a higher cortisol in both groups while non-caregivers had higher cortisol than caregivers. Conclusions. If the findings can be replicated, the implementation of interventions to support informal caregivers in managing their chronic stress and modify their NAS appears warranted.

Background: The potential association of the ABO blood group with the risk of COVID-19 and its severity has attracted a lot of interest since the start of the pandemic. While a number of studies have reported an increased risk associated with blood type A and a reduced risk with type O, other studies have did not found a significant effect. This study aimed to define the prevalence of different ABO blood groups in hospitalized COVID-19 patients in the Louisville, KY area and to investigate whether an association exists between the blood group and disease severity. Methods: This was a retrospective observational study of 380 patients with SARS-CoV-2 infection hospitalized to eight of the adult hospitals in the city of Louisville. Patients were divided into four different groups according to their ABO blood type. Demographic characteristics and clinical variables, including laboratory data as well as clinical outcomes were compared. Results: Type O was the most common blood group among the hospitalized patients (51%) followed by type A (31%), B (14%) and AB (4%). The observed blood group distribution among the patients was not significantly different from the distribution expected when compared to a population of similar racial/ethnic composition. No significant associations were found between the blood group and comorbidities, inflammatory biomarkers as well as with recorded outcomes, including the mortality rate and the length of the hospital stay. Conclusions: The data from hospitalized patients in Louisville is is not consistent with the ABO blood group having a significant effect as a risk or severity factor for COVID-19, but it is representative in COVID-19 or its severity of its prevalence among different racial/ethnic populations.

We examined the effect of informal cancer caregiver stress and negative attribution style (NAS) on depressive symptoms and salivary cortisol.The sample came from a hospital bone marrow unit and caregiver support organizations and included 60 informal cancer caregivers (51.7% partners) of individuals with cancer (provided care for a median of 27.5 h per week for 12 months) and 46 non-caregiver participants. In this cross-sectional study, participants completed questionnaires assessing NAS and depressive symptoms and provided saliva samples to measure cortisol.Linear regressions demonstrated that cancer caregiver stress (p = 0.001) and the cancer caregiver stress by NAS interaction (p = 0.017), but not NAS alone (p = 0.152), predicted depressive symptoms. Caregivers independent of their NAS and non-caregivers high in NAS reported high depression while non-caregivers low in NAS reported low depression. Neither cancer caregiver stress (p = 0.920) nor NAS alone (p = 0.114), but their interaction, predicted cortisol (p = 0.036). Higher NAS was associated with a higher cortisol in both groups while non-caregivers had higher cortisol than caregivers.If the findings can be replicated, consideration of NAS in existing interventions to support informal cancer caregivers in managing chronic stress appears warranted.

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.

Objectives To examine the effect of informal cancer caregiving and repetitive negative thinking (RNT) on depressive symptoms and salivary cortisol levels. Sample & setting The sample was recruited from a hospital bone marrow unit and caregiver support organizations. It included 60 informal cancer caregivers (52% partners) of individuals with cancer who provided care for a median of 27.5 hours per week for 12 months, and 46 noncaregiver participants. Methods & variables In this cross-sectional study, participants completed questionnaires assessing RNT and depressive symptoms and provided saliva samples to measure cortisol levels. Results Cancer caregiving and RNT, but not the interaction, were associated with more depressive symptoms. RNT, but not cancer caregiving, was associated with salivary cortisol. A disordinal interaction effect suggests that cancer caregiving was associated with lower cortisol levels, and RNT in noncaregivers was associated with higher cortisol levels. Implications for nursing Given that RNT is related to depressive symptoms and cortisol, connecting cancer caregivers who experience RNT to resources and the development and evaluation of brief nurse-led interventions to reduce RNT in informal cancer caregivers seems warranted.

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 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-1β 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-1β, Th17-family cytokines and gut permeability between HIV-positive vs. negative individuals require further study.

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-1β 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.

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.

To better understand how trauma leads to poor health, this study examined whether cumulative trauma and emotion reactivity contribute to pro- (IL-1β) and anti-inflammatory (IL-10) salivary cytokine levels after stress.Seventy-three women, screened to be physically and mentally healthy, completed an acute stress paradigm and measures of lifetime trauma exposure.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.Most participants reported exposure to at least one trauma, with a mean of five. Cumulative trauma was associated with higher post-stress IL-1β and IL-1β/IL-10, but not with IL-10 or changes in emotion. Declines in positive emotion correlated with greater post-stress IL-1β.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.

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

Elevated inflammation in the context of stress has been implicated in mental and physical health. Approaching this from an emotion regulation perspective, we tested whether the salivary cytokine response to stress is dampened by using distraction to minimize opportunity for poststressor rumination. Healthy young adults were randomized to an acute stressor: modified Trier Social Stress Test (TSST, Study 1) or angry memory retrieval (Study 2). Within each study, participants were randomized to poststressor condition-rest or distraction-at a 3:1 ratio. Saliva, collected before and 40 min after the end of each stressor, was assayed for proinflammatory cytokines (PICs): interleukin-1β (IL-1β), TNF-α, and IL-6. Both stressors increased all PICs, and both provoked negative emotion. At 40 min post-TSST, salivary PIC increases did not differ between distraction and rest, but correlated positively with emotional reactivity to stress. At 40 min after memory retrieval, IL-1β increases and intrusive rumination were lower during distraction than rest, but did not correlate with emotional reactivity. Trait rumination and interference control mechanisms, also measured, played little role in PIC increases. Overall, after some stressors, some salivary cytokine responses are lower during distraction than rest. The roles of specific emotions, emotional intensity, and poststressor timing of saliva collection in this finding require clarification. Furthermore, the possibility of two affective paths to inflammation in the context of stress-one sensitive to opportunities for early occurring emotion regulation (as reflected in emotional reactivity), and one sensitive to late-occurring emotion regulation (as reflected in distraction after stress)-deserves attention. (PsycINFO Database Record

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.

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. UCR::Vicerrectoría de Investigación::Unidades de Investigación::Ciencias de la Salud::Instituto de Investigaciones en Salud (INISA)

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.

This cross-sectional study compared the prevalence of formal and informal sheltering (i.e., staying in an agency shelter, or with friends/family, respectively) and evaluated associations with abuse severity. Community women ( N = 197) with divorce histories reported on lifetime intimate partner abuse, including sheltering for safety. Prevalence of informal sheltering (43%) exceeded that of formal sheltering (11%). Rates/levels of coercive control, severe violence, injury, and police involvement were comparable for women who sheltered formally or informally, and exceeded those of women who never sheltered. Sheltering histories can be identified in community samples of women with divorce histories. Informal sheltering is prevalent, and comparable to formal sheltering in terms of correlations with abuse severity.

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. 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. 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. 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.

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.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.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).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.

Introduction Patients with severe community-acquired pneumonia (CAP) are believed to have an exaggerated inflammatory response to bacterial infection. Therapies aiming to modulate the inflammatory response have been largely unsuccessful, perhaps reflecting that CAP is a heterogeneous disorder that cannot be modulated by a single anti-inflammatory approach. We hypothesize that the host inflammatory response to pneumonia may be characterized by distinct cytokine patterns, which can be harnessed for personalized therapies. Methods Here, we use hierarchical cluster analysis of cytokines to examine if patterns of inflammatory response in 13 hospitalized patients with CAP can be defined. This was a secondary data analysis of the Community-Acquired Pneumonia Inflammatory Study Group (CAPISG) database. The following cytokines were measured in plasma and sputum on the day of admission: interleukin (IL)-1β, IL-1 receptor antagonist (IL-1ra), IL-6, CXCL8 (IL-8), IL-10, IL-12p40, IL-17, interferon (IFN)γ, tumor necrosis factor (TNF)α, and CXCL10 (IP-10). Hierarchical agglomerative clustering algorithms were used to evaluate clusters of patients within plasma and sputum cytokine determinations. Results A total of thirteen patients were included in this pilot study. Cluster analysis identified distinct inflammatory response patterns of cytokines in the plasma, sputum, and the ratio of plasma to sputum. Conclusions Inflammatory response patterns in plasma and sputum can be identified in hospitalized patients with CAP. Characterization of the local and systemic inflammatory response may help to better discriminate patients for enrollment into clinical trials of immunomodulatory therapies.

SummaryInflammation is a double-edged sword in the outcome of pneumonia. On the one hand, an effective and timely inflammatory response is required to eliminate the invading respiratory pathogen. On the other, a toxic and prolonged inflammatory response may result in lung injury and poor outcomes, even in those receiving advanced medical care. This review focuses on recent understanding of the dynamics of the cytokine response, neutrophil activity, and responsiveness to cytokines and neutrophil lifespan as major elements of lung inflammation resulting in favorable or poor outcomes in lung infection primarily due to pneumococcus and influenza virus. Although some progress has been made in our understanding of the molecular mechanisms of the pneumonia inflammation axis composed of cytokines modulating neutrophil activation and neutrophil apoptosis, important questions remain to be answered. The degree of neutrophil activation, generation of reactive oxygen species, and the release of granule antimicrobial peptides play a key role in microbial pathogen clearance; however, prolonged neutrophil activation may contribute to lung injury and poor outcomes in pneumonia. Molecular markers of the mechanisms regulating neutrophil survival and apoptosis may help in the identification of novel therapeutic targets to modulate inflammation by inducing timely neutrophil apoptosis. A major task is to identify the mechanisms of dysregulation in inflammation leading to toxic responses, thereby targeting a biomarker and enabling timely therapies to modulate inflammation.

Background: Curcumin is a well-established natural molecule with significant biological and pharmaceutical effects. Its effects on Helicobacter pylori (H. pylori) infection have been repeatedly confirmed both in animal and human models. This study directly compared five different samples to evaluate if the effects are general or if they differ among samples. Methods: Using a mouse model, we studied the effects of curcumin on lipid peroxide (LPO) level, myeloperoxidase (MPO) and urease activity, number of colonized bacteria, levels of anti-H. pylori antibodies, biofilm formation, IFN-γ, IL-4, gastrin and somatostatin levels in serum, and minimum inhibitory concentration. In addition, we evaluated the effects on biofilm production and antibacterial antibody response. Results: In all tests, one sample (Sabinsa) was consistently the most active. Conclusions: All curcumin samples showed some anti-H. pylori effects, but only some of the tested samples had significant activity.

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-1β, 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-1β/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.

Background The role and relationship between pro- and anti-inflammatory cytokines represents one of the least studied aspects of the pathogenesis of community-acquired pneumonia (CAP). The aim of the present study was to evaluate pro- and anti-inflammatory cytokines at both local (lung) and systemic (blood) levels and their relationship with the severity of the disease on admission and time for a patient to reach clinical stability during hospitalisation. Methods This was an observational, prospective, cohort study of hospitalised patients with a diagnosis of CAP at the IRCCS Policlinico Hospital, Milan, Italy, between April 2010 and January 2012. Ten pro-inflammatory cytokines (interleukin [IL]-1, IL-1α, IL-1β, IL-2, IL-6, IL-8, tumor necrosis factor [TNF]α and interferon [IFN]γ) and anti-inflammatory cytokines (IL-4 and IL-10) were measured in both serum and exhaled breath condensate within 24 h after hospital admission. Results A total of 74 patients (median age: 76 years; gender: 61 % male) were enrolled. The anti- to pro-inflammatory cytokine ratio was reduced in patients with severe disease on admission and prolonged time to reach clinical stability. This was due to lower levels of anti-inflammatory cytokines in the exhaled breath condensate and higher levels of pro-inflammatory cytokines in serum. Conclusions Dis-regulation between pro- and anti-inflammatory pathways might be a part of the pathogenic mechanisms that lead to severe infection and worse early clinical outcomes in CAP patients. Electronic supplementary material The online version of this article (doi:10.1186/s41479-016-0009-7) contains supplementary material, which is available to authorized users.

Subjective sleep quality refers to perceived ease of falling asleep, staying asleep, and obtaining adequate sleep that leaves one feeling rested. Such perceptions do not necessarily correspond to objective measures of sleep quality provided by polysomnography. Nevertheless, they are the key to diagnosing some sleep disturbances, such as insomnia (1). Insomnia can be treated, and subjective sleep quality improved, by interventions that help people identify and change beliefs and behaviors that interfere with sleep (2). Livingston et al. (3) examined whether responses to such cognitive–behavioral interventions are associated with changes in the expression of genes involved in the regulation of inflammation. Participants were 68 active duty United States military personnel (97% males) seeking sleep evaluations. All had been deployed within the previous 18 months and had current diagnoses of insomnia or insomnia comorbid with obstructive sleep apnea. Probable syndromal depression or posttraumatic stress disorder (PTSD) was present in 47 and 28% of participants, respectively. Participants were assessed before, and immediately after, completing treatment for insomnia (cognitive–behavioral therapy for insomnia) or for comorbid insomnia and obstructive sleep apnea (either sleep education or cognitive–behavioral therapy for insomnia combined with positive airway pressure). Assessments included subjective sleep quality, depression and posttraumatic stress symptoms, and peripheral blood gene expression profiles. After 3 months of treatment, two clusters of participants were identified, those with any improvement in subjective sleep quality (68% of the sample) and those without any improvement (32% of the sample). The former group, compared to the latter, showed decreases in symptoms of depression from pre- to posttreatment. Microarray data identified 217 genes, whose expression was differentially altered in those participants with improved sleep. Consistent with reduced inflammation, downregulated genes included those for key proinflammatory cytokines [interleukin (IL)-1β, IL-6, and TNF-α] and chemokines (CCL3, 4, and 5). Among the upregulated genes were also inflammation/immune response-associated genes, including several toll-like receptors (TLR1, 4, 7, and 8) and cytokine/chemokine receptors (i.e., IFNγR1 and the IL-8R) as well as stress-related genes. Analysis of the gene expression data using ingenuity pathway analysis (IPA) (4) identified six gene networks, including ubiquitin. Insomnia is an important clinical problem in its own right. In addition, it is increasingly recognized as a contributory factor in multiple mental and physical health problems (5–7), including those that arise post-trauma (5). Connections between insomnia and health problems may partially reflect the importance of sleep in regulating adaptive and innate immunity (8). Indeed, disturbances in sleep that include insomnia and poor subjective sleep quality are associated with elevations in systemic inflammation (9). Critically, Livingston and colleagues identified potentially salutary changes in gene expression among trauma-exposed persons who responded favorably to cognitive–behavioral sleep interventions. Their results provoke questions about whether interventions for sleep disturbances might feed-forward to promote better health and protect against the emergence of health problems after trauma exposure. While reduction in the expression of key proinflammatory cytokine/chemokine genes is consistent with reduced inflammation as a potential mechanism, the relevance of changes in the expression of other genes, such as those for immune receptors and stress-related molecules, remains to be further investigated. Several directions for future research are suggested by this preliminary investigation. Regarding the sample, it will be important to test whether results generalize to sleep disturbances that arise in the context of exposure to other traumatic stressors; sleep disturbances in military personnel are determined by myriad factors that may not apply in other contexts (e.g., time zone changes and potential circadian disruption, long and varying work shifts, and health behaviors used to manage these challenges) (10). Similarly, testing whether these results extend to trauma-exposed women is a high priority, given sex and gender differences in multiple aspects of sleep (11). Regarding the intervention, controlled trials will be necessary to determine whether improved subjective sleep quality is due to the intervention per se, as opposed to the passage of time or non-specific factors. A recent randomized controlled trial for later-life insomnia provides evidence for the specific value of cognitive–behavioral interventions, including for salutary changes in gene expression (12). Also, the persistence of the effects over time should be addressed. Regarding the results, because the cognitive–behavioral sleep interventions were associated with improved gene expression profiles in a subset of insomnia patients – those with improved sleep quality after treatment – the next logical step is to identify factors that differentiate treatment responders from non-responders. Also, microarray data of the key genes need to be further validated and more mechanistic studies performed. Finally, the interplay of sleep quality improvements, depression reductions, and gene expression requires attention – what is the order of the causal chain and are reciprocal influences present? Among trauma-exposed persons, sleep disturbances do not always respond to interventions for PTSD. Even when participants no longer meet diagnostic criteria for syndromal PTSD, clinically significant sleep disturbances may persist (13, 14). Similarly, in observational studies, trauma history helps explain clinically significant sleep disturbances, independent of current mental health symptoms (15). Thus, among trauma-exposed persons, sleep problems may not always be by-products of other mental health problems. The results of Livingston et al. (3) raise the intriguing question of whether specifically addressing such sleep problems, in addition to other post-trauma stress reactions, might yield broader health benefits for trauma-exposed persons.

Lifetime occurrence of intimate partner violence (IPV) in women has been associated with increased prevalence of aging-related chronic diseases, including those with a pathophysiology involving inflammation. To begin to identify potential biologic mediators of this relationship, this cross-sectional study examined associations between past IPV and circulating levels of C-reactive protein (CRP) and interleukin-6 (IL-6)-measures linked with emergence of aging-related diseases-along with in vitro IL-6 production by peripheral blood mononuclear cells (PBMC) stimulated with either phytohemagglutinin A (PHA) or lipopolysaccharide (LPS).Apparently healthy, midlife women with divorce histories were recruited from the community. Histories of intimate partner psychological aggression, physical assault, sexual coercion, and stalking were assessed, along with current depression, posttraumatic stress symptoms, and health-related characteristics. At two visits, blood was drawn for assessment of biologic measures; measures were averaged across visits.In this sample (n=68), a history of being stalked was significantly positively correlated with CRP levels; in a multiple regression analysis that included body mass index (BMI) and current symptoms, this association was attenuated by adjusting for BMI. Physical assault history was significantly negatively correlated with PHA-stimulated IL-6 production. This was most apparent for severe assault and was not accounted for by BMI or symptoms.IPV histories remitted for an average of 10 years were associated with biologic mediators of inflammation. The profile was not uniformly proinflammatory, suggesting that in situations of traumatic or chronic stress, different aspects of the inflammatory response are differentially regulated and subjected to diverse compensatory mechanisms.

Although little is known about the etiology of progressive supranuclear palsy (PSP), genetic and epigenetic factors, oxidative injury and inflammation are thought to contribute to its development and/or progression. Evidence for activated glia involvement in PSP has raised the possibility that neuroinflammation may contribute to its pathogenesis. To investigate the correlation between neuroinflammation and PSP, a comparative study was conducted on the patterns of cytokine expression in different regions of the brains of PSP, Alzheimer's disease (AD) patients and normal controls. Our results show different patterns of cytokine expression in each disease, with the expression of IL-1β transcripts being significantly higher in the substantia nigra of PSP than in AD and controls, while AD brains had significantly higher IL-1β expression in the parietal cortex compared to PSP and controls. In addition, expression of TGFβ was significantly higher in the cortical areas (particularly frontal and parietal lobes) of AD compared to PSP and controls. These results show a disease-specific topographical relationship among the expression of certain cytokines (IL-1β and TGFβ), microglial activation and neurodegenerative changes, suggesting that these cytokines may contribute to the pathologic process. If so, the use of cytokine-inhibitors and/or other anti-inflammatory agents may be able to slow disease progression in PSP.

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 M. 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 ten HIV+ women who went on to 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 ten 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 six to twelve months 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.

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.

Acute and chronic psychological stress are known to trigger components of the inflammatory system resulting in increased levels of pro-inflammatory cytokines (i.e., IL-1β, IL-6 and TNFα). Stress can also result in the activation of the coagulation and fibrinolytic systems via the sympathoadrenal medullary system, resulting in net hypercoagulability. The aim of this study was to investigate the effects of acute stress on the salivary levels of a key component of the fibrinolytic system, urokinase plasminogen activated receptor (uPAR) and determine the relationship with changes in pro- and anti-inflammatory cytokines. Healthy subjects, ages 18–40 (74% female), were randomly assigned to complete a modified Trier Social Stress Test (n = 44) or to recall an angry autobiographical memory (n = 46). Saliva samples, taken at baseline and 60 min post-stress, were used to measure levels of cytokines and uPAR. Acute stress resulted in a significant increase in the salivary levels of uPAR (p

Glycosaminoglycans (GAGs) located on cellular membranes and the extracellular matrix (ECM) are able to interact with chemokines and pro-inflammatory cytokines, leading to local cytokine/chemokine accumulation. The tissue-bound cytokines/chemokines function in promoting leukocyte migration and activation, contributing to local inflammation. Hence, targeting of GAG–cytokine interactions may provide an avenue for the attenuation of inflammatory responses. A cationic peptide (MC2) derived from the heparin-binding sequence of mouse IFN-γ was previously shown by our laboratory to delay allograft rejection in an animal model. In order to further investigate potential anti-inflammatory properties of the MC2 peptide, we have studied its activity in an acute peritoneal inflammation model. Groups of C57Bl/6 mice were injected intraperitoneally with either ConA or thioglycollate and treated with saline (control), the MC2 peptide or two control cationic peptides, poly- l -lysine (PLL) and poly- l -arginine (PLA). Treatment with the MC2 peptide, but not PLA or PLL, resulted in statistically significant reductions in total cell numbers, concentration of total proteins and concentrations of pro-inflammatory cytokines (TNFα, IL-6 or IL-1β) in peritoneal lavage fluids, without alterations to the qualitative cellular composition of the exudate. These results suggest that targeting GAG–cytokine interaction is a viable approach to reduce inflammation.

Glycosaminoglycans (GAGs) play an important role in inflammatory responses due to their ability to interact with cytokines and chemokines, resulting in the localization of these mediators to specific anatomical sites, where they function to direct leukocyte recruitment and activation. Targeting GAG-cytokine/chemokine interactions might may thus have therapeutic applications as anti-inflammatory or immunomodulatory therapy in vivo. Peptides that mimic the heparin-binding domains of cytokines may have a potential use as inhibitors of GAG-cytokine interactions. A linear octapeptide (MC-2) derived from the conserved heparin-binding region of interferon-gamma (IFN-gamma) was synthesized along with four analogs featuring a substitution of Phe for Leu in position 1 and varying number of positive charges on the octapeptide molecule. The relative abilities of the synthesized peptides to inhibit the interactions between IFN-gamma and GAGs were compared. From the results, it follows that the inhibitory potency of the octapeptide analogs was related to the number of positive charges in the molecule, while increased hydrophobicity had no significant effect.

Although several recent studies suggest that dopamine may have a significant role in the regulation of immune cell function, the mechanisms involved remain unclear. We undertook this study to clarify the actions of dopamine in vivo on lymphocyte proliferation and to determine whether such effects are mediated by alterations in interleukin-2 (IL-2) production and/or IL-2 receptor (IL-2R) expression. Administration of the dopamine precursor, L-dopa, for 5 days to BALB/c mice significantly increased Concanavalin A (ConA)-induced proliferation of lymphocytes. This effect was blocked by treatment with dopamine receptor antagonists as well as a peripheral dopamine synthesis inhibitor, suggesting a peripheral action of dopamine. L-dopa treatment had no effect on IL-2 production or IL-2R expression, indicating that the effects of dopamine on lymphocyte proliferation are not indirectly mediated by alterations in the IL-2 system.

A marital status of divorced or separated, as opposed to married, predicts increased risk of health problems, but not for all persons. Focusing on one established health risk that has been linked with divorce—poor subjective sleep quality—the present cross-sectional study examined whether a history of physical intimate partner victimization (IPV) helps identify divorced women at potentially greater risk of health problems. Community midlife women with divorce histories, all of whom were free of current IPV, reported on their past month sleep quality and lifetime IPV. The predicted odds of poor sleep quality were significantly greater for women with, versus without, IPV histories. This held after adjusting for socioemotional, medical, or sociodemographic risks. A dose–response relationship between IPV chronicity and poor quality sleep was observed. IPV history may help identify divorced women at increased risk of poor quality sleep and, more broadly, poor health.

Background Glycosaminoglycans (GAGs) are heteropolysaccharides present as integral components of the extracellular matrix (ECM), cell and basement membranes. GAGs play an important role in immune and inflammatory responses because of their ability to interact with cytokines and chemokines, promoting the localization of these molecules onto the ECM or cell membranes at specific anatomical sites. The main goal of these studies was to test the hypothesis that interference with the binding of cytokines/chemokines to GAGs will interfere with a graft rejection response. Methods MC-2, a cationic peptide derived from the sequence of the heparin-binding domain of mouse interferon gamma, was used as an inhibitor of the binding of cytokines/chemokines to GAGs. The effects of this peptide were studied in an allogeneic transplantation model involving vascularized rat skin flaps. Results The MC-2 peptide was found to inhibit binding of interferon-gamma, as well as that of the chemokines, interleukin-8, interferon gamma inducible protein-10, and regulated on activation normal T cell expressed and secreted (RANTES), to GAGs in vitro. Direct administration of MC-2 in an allogeneic skin flap transplantation model resulted in a significantly delayed time of rejection, from 5.4 +/- 0.5 days (control; n=6) to 12.6 +/- 1.6 days (treated animals; n=10). Histopathologic analysis of the skin biopsies was consistent with the delayed rejection process in those animals receiving the peptide, showing only mild signs of rejection up to day 11 (in contrast, all control animals had rejected their flaps by day 6). Conclusions These results are consistent with the idea that GAG-cytokine interactions constitute valid therapeutic targets and suggest the potential applicability of such an approach in the prevention of graft rejection.

Further examination of clinical outcomes and inflammatory response of bacteremic pneumococcal community-acquired pneumonia (CAP) is of great interest to enhance the care of patients with pneumococcal CAP. This is a secondary analysis of the Community Acquired Pneumonia Organization (CAPO) to compare the time to clinical stability (TCS), length of hospital stay (LOS), and in-hospital mortality of hospitalized pneumococcal CAP patients with and without bacteremia. To measure the effect of bacteremia in pneumococcal CAP patients on outcomes, we modeled all-cause in-hospital mortality using a Poisson regression model, and TCS and LOS using Cox proportional hazards models. Adjusted multivariate regression models were also used to predict the probability of occurrence of each of the study outcomes. To investigate the inflammatory response, we measured the plasma levels of pro- and anti-inflammatory cytokines [tumor necrosis factor (TNF)-α, interleukin (IL)-1rα, IL-6, IL-8, IL-10], inflammatory biomarkers [C-reactive protein (CRP), pro-calcitonin (PCT), and B-type natriuretic peptide (BNP)], and peripheral blood neutrophil responses in 10 patients, 4 bacteremic and 6 non-bacteremic pneumococcal CAP, upon admission and every other day during the first 6 days of hospitalization. Functional data were presented as median and standard error of the median (SEM); due to small number of samples no statistical comparisons were performed between groups. From 833 pneumococcal CAP patients, 394 patients (47 %) were bacteremic. Bacteremic pneumococcal CAP were less likely to reach TCS with an adjusted hazard ratio (AHR) of 0.82 (95 % CI 0.69–0.97; p = 0.02) and had higher in-hospital mortality with an AHR of 1.63 (95 % CI 1.06–2.50, p = 0.026). Bacteremic pneumococcal CAP patients had a longer LOS than non-bacteremic pneumococcal CAP (p