Global cervical cancer research: A scientometric density equalizing mapping and socioeconomic analysis.

Cervical cancer has caused substantial morbidity and mortality for millions of women over the past decades. While enormous progress has been made in diagnosis, prevention and therapy, the disease is still fatal for many women-especially in low-income countries. Since no detailed studies are available on the worldwide research landscape, we here investigated the global scientific output related to this cancer type by an established protocol. The "New Quality and Quantity Indices in Science" platform assessed all relevant cervical cancer research published in the Web of Science since 1900. A detailed analysis was conducted including country-specific research productivity, indicators for scientific quality, and relation of research activity to socioeconomic and epidemiologic figures. Visualization of data was generated by the use of density equalizing map projections. Our approach identified 22,185 articles specifically related to cervical cancer. From a global viewpoint, the United States of America was the dominating country in absolute numbers, being followed by China and Japan. By contrast, the European countries Sweden, Austria, and Norway were positioned first when the research activity was related to the population number. When the scientific productivity was related to annual cervical cancer cases, Scandinavian countries (Finland #1, Sweden #4, Norway #5, Denmark #7), the Alpine countries Austria (#2) and Switzerland (#6), and the Netherlands (#3) were leading the field. Density equalizing mapping visualized that large parts of Africa and South America were almost invisible regarding the global participation in cervical cancer research. Our data documented that worldwide cervical cancer research activity is continuously increasing but is imbalanced from a global viewpoint. Also, the study indicated that global and public health aspects should be strengthened in cervical carcinoma research in order to empower more countries to take part in international research activities.

Secondary heterologous dengue infection risk: Disequilibrium between immune regulation and inflammation?

Increased serum levels of cytokines released by cells of the immune response have been detected in patients suffering from dengue disease. Likewise, secondary infections by a different dengue virus serotype result in a highest risk of development of the severe dengue disease. Both findings suggest that the memory immune response is one of the key players in the pathogenesis of this disease. Here we take advantage of the particular Cuban epidemiological situation in dengue to analyze a broad spectrum of cell-mediated immune response mediators at mRNA and protein level. Evidences for a regulatory immune pattern in homologous (TGF-beta, IL-10) vs. pro-inflammatory pattern (IFN-gamma, TNF-alpha) in heterologous dengue virus re-challenge were found, suggesting a possible association with the higher incidence of severe dengue cases in the latter case.

MCP-1 and MIP-1α expression in a model resembling early immune response to dengue.

Dengue virus has become endemic in most tropical urban areas throughout the world, and DHF has appeared concomitantly with this expansion. The intensity of dengue virus replication during the early stages of infection could determine clinical outcomes; therefore, it is important to understand the impact of dengue virus infection on the earliest immune defense against microbial infection, which also strongly regulates the adaptive immune responses. This study was aimed at evaluating the expression of the CC-chemokines MIP-1α/CCL3 and MCP-1/CCL2 in peripheral blood leukocytes using an ex vivo model resembling dengue infection in vivo, in subjects with a well characterized dengue immune background, due to the exceptional Cuban epidemiological situation in dengue. The expression of IFNγ, TNFα and IL10 was also evaluated, giving insight about the role of MCP-1 and MIP-1α in the interplay between innate and adaptive immunity. From individuals with different dengue immune background after dengue virus challenge, increased and different expression of the chemokines and cytokines studied was verified in peripheral blood mononuclear cells, thus demonstrating that the previous immunity to a dengue virus serotype has a strong influence on the early immune response after dengue re-infection.

Variation in inflammatory/regulatory cytokines in secondary, tertiary, and quaternary challenges with dengue virus.

Secondary heterologous dengue infection is a risk factor for severe disease manifestations because of the immune-enhancement phenomenon. Succeeding clinical infections are seldom reported, and the clinical course of tertiary and quaternary dengue infections is not clear. Cuba represents a unique environment to study tertiary/quaternary dengue infections in a population with known clinical and serologic dengue markers and no dengue endemicity. We took advantage of this exceptional epidemiologic condition to study the effect of primary, secondary, tertiary, and quaternary dengue infection exposure on the expression of pro-inflammatory and regulatory cytokines, critical in dengue infection pathogenesis, by using a dengue infection ex vivo model. Whereas secondary exposure induced a high cytokine response, we found a significantly lower expression of tumor necrosis factor-α, interferon-γ, interleukin-10, and tumor growth factor-ß after tertiary and quaternary infectious challenge. Significant differences in expression of the cytokines were seen between the dengue immune profiles, suggesting that the sequence in which the immune system encounters serotypes may be important in determining the nature of the immune response to subsequent infections.

Clinical manifestation of mannose-binding lectin deficiency in adults independent of concomitant immunodeficiency.

Mannose-binding lectin (MBL) mediates important functions within the innate immune system, and its deficiency was associated with infectious complications. However, in adults without concomitant immunodeficiency the clinical relevance of MBL deficiency remains controversial. We analyzed the distribution of MBL deficiency and its association with concomitant immunodeficiency in 228 adult Caucasian patients with a history of recurrent and/or severe infections. Two hundred forty-one unrelated Caucasians without recurrent or severe infections served as control subjects. The frequency of severe MBL deficiency (plasma levels

Rapid whole blood flow cytometric test to detect ICOS deficiency in patients with common variable immunodeficiency.

BACKGROUND/AIMS: Common variable immunodeficiency (CVID) is the most common primary immunodeficiency. With respect to underlying defects it comprises a heterogeneous group of deficiencies. For some patients, distinct phenotypical abnormalities have been described, e.g. partial CD40L deficiency or complete ICOS deficiency. For the diagnosis of CD40L deficiency, a rapid whole blood flow cytometric method has been described several years ago. We aimed to determine if the same method can be used to diagnose ICOS deficiency. METHODS: Whole blood from 8 healthy volunteers was stimulated for 4 and 20 h with phorbol 12-myristate 13-acetate (PMA) and ionomycin. Induction of ICOS expression was analyzed on CD8-CD3+ lymphocytes using three-color flow cytometry. Blood from a patient with diagnosed ICOS deficiency was also analyzed. RESULTS: Whole-blood stimulation with PMA and ionomycin for 20 h resulted in a significant induction of ICOS expression on CD8-CD3+ lymphocytes in healthy volunteers. Four-hour incubation also demonstrated ICOS upregulation but to a much lower extent. In CD8-CD3+ lymphocytes from an ICOS-deficient patient, no ICOS expression could be induced following 20 h of stimulation. CONCLUSION: ICOS expression can be analyzed using a rapid whole blood flow cytometric test.

CD31+ naïve Th cells are stable during six months following kidney transplantation: implications for post-transplant thymic function.

Little is known about thymus function in transplant patients. Until recently, the phenotype of T cells that recently emigrated the thymus was unknown. Now it has been demonstrated that CD4(+) recent thymus emigrants coexpress CD31 and CD45RA. Here, we investigated whether uremia and immunosuppression influence CD31(+) CD45RA(+) Th cells before and after kidney transplantation, respectively. Forty-eight renal transplant patients were included receiving either standard triple/quadruple (n = 35) immunosuppression, OKT-3 induction (n = 7) or FTY-720 (n = 6), respectively. Peripheral CD31(+) CD45RA(+) Th cells were quantified flowcytometrically before and at week 1, 4, 12 and 24 post-transplantation. Thirty-nine healthy adults served as controls. CD31(+) CD45RA(+) Th cells correlated inversely with age in patients and controls and were comparable in patients before transplantation and age-matched controls. Importantly, CD31(+) CD45RA(+) Th cell frequencies remained stable during 6 months post-transplantation. In conclusion, CD31(+) CD45RA(+) Th cells are not significantly altered by uremia before and during 6 months of immunosuppressive therapy after kidney transplantation. Implications for thymus function are discussed.

Monitoring temporary immunodepression by flow cytometric measurement of monocytic HLA-DR expression: a multicenter standardized study.

BACKGROUND: Single-center trials have shown that monocytic HLA-DR is a good marker for monitoring the severity of temporary immunodepression after trauma, major surgery, or sepsis. A new test for measuring monocytic HLA-DR is now available. METHODS: We evaluated a new test reagent set for monocytic HLA-DR expression (BD Quantibritetrade mark HLA-DR/Monocyte reagent; Becton Dickinson) in single-laboratory and interlaboratory experiments, assessing preanalytical handling, lyse-no-wash (LNW) vs lyse-wash (LW) values, reference values, and the effect of use of different flow cytometers and different instrument settings on test variance. RESULTS: For preanalytical handling, EDTA anticoagulation, storage on ice as soon as possible, and staining within 4 h after blood collection gave results comparable to values obtained for samples analyzed immediately after collection (mean increase of approximately 4% in monocytic HLA-DR). Comparison of LNW and LW revealed slightly higher results for LNW ( approximately 18% higher for LNW compared with LW; r = 0.982). Comparison of different flow cytometers and instrument settings gave CVs <4%, demonstrating the independence of the test from these variables and suggesting that this method qualifies as a standardized test. CV values from the interlaboratory comparison ranged from 15% (blood sample unprocessed before transport) to 25% (stained and fixed before transport). CONCLUSIONS: For the BD Quantibrite HLA-DR/Monocyte test, preanalytical handling is standardized. Single-laboratory results demonstrated the independence of this test from flow cytometer and instrument settings. Interlaboratory results showed greater variance than single-laboratory values. This interlaboratory variance was partly attributable to the influence of transport and can be reduced by optimization of transport conditions.