Bacterial meningitis: a density-equalizing mapping analysis of the global research architecture.

Bacterial meningitis is caused by a variety of pathogens and displays an important public health threat all over the world. Despite the necessity to develop customized public health-related research projects, a thorough study of global meningitis research is not present, so far. Therefore, the aim of this study was a combined density-equalizing and scientometric study. To evaluate the scientific efforts of bibliometric methods, density-equalizing algorithms and large-scale data analysis of the Web of Science were applied in the period between 1900 and 2007. From this, 7998 publications on bacterial meningitis have been found. With a number of 2698, most publications have been written by U.S. authors, followed by the UK (912), Germany (749) and France (620). This dominance can also be shown in the international cooperation. The specific citation analyses reveal that the nation with the highest average citation rate (citations per publications) was Norway (26.36), followed by Finland (24.16) and the U.S. (24.06). This study illustrates the architecture of global research on bacterial meningitis and points to the need for customized research programs with a focus on local public health issues in countries with a low development index, but high incidences, to target this global public health problem.

Traffic medicine-related research: a scientometric analysis.

OBJECTIVE: Traffic crashes and related injuries are important causes of morbidity and mortality and impose insofar an important burden on public health. However, research in this area is often under-funded. The aim of this study was to analyse quantity, evolution and geographic distribution of traffic medicine-related research. This multi-sectorial field covers both transport and health care sectors. DESIGN: A scientometric approach in combination with visualizing density equalizing mapping was used to analyse published data related to the field of traffic medicine between 1900 and 2008 within the "Web of Science" (WoS) database. RESULTS: In total, 5,193 traffic medicine-associated items were produced between 1900 and 2008. The United States was found to have the highest research activity with a production of n = 2,330 published items, followed by Germany (n = 298) and Canada (n = 219). Cooperation analyses resulted in a peak of published multilateral cooperations in the year of 2003. The country with the highest multilateral activity was the USA. The average number of cited references per publication varied heavily over the last 20 years with a maximum of 27.67 in 1995 and a minimum of 15.08 in 1998. Also, a further in-depth analysis was performed with a focus solely on public health aspects which revealed similar trends. CONCLUSIONS: Summarizing the present data it can be stated traffic medicine-related research productivity grows annually. Also, an active networking between countries is present. The data of the present study may be used by scientific organisations in order to gain detailed information about research activities in this field which is extremely important for public health.

IgM+IgD+CD27+ B cells are markedly reduced in IRAK-4-, MyD88-, and TIRAP- but not UNC-93B-deficient patients.

We studied the distribution of peripheral B-cell subsets in patients deficient for key factors of the TLR-signaling pathways (MyD88, TIRAP/MAL, IL-1 receptor-associated kinase 4 [IRAK-4], TLR3, UNC-93B, TRIF). All TLRs, except TLR3, which signals through the TRIF adaptor, require MyD88 and IRAK-4 to mediate their function. TLR4 and the TLR2 heterodimers (with TLR1, TLR6, and possibly TLR10) require in addition the adaptor TIRAP, whereas UNC-93B is needed for the proper localization of intracellular TLR3, TLR7, TLR8, and TLR9. We found that IgM(+)IgD(+)CD27(+) but not switched B cells were strongly reduced in MyD88-, IRAK-4-, and TIRAP-deficient patients. This defect did not appear to be compensated with age. However, somatic hypermutation of Ig genes and heavy-chain CDR3 size distribution of IgM(+)IgD(+)CD27(+) B cells were not affected in these patients. In contrast, the numbers of IgM(+)IgD(+)CD27(+) B cells were normal in the absence of TLR3, TRIF, and UNC-93B, suggesting that UNC-93B-dependent TLRs, and notably TLR9, are dispensable for the presence of this subset in peripheral blood. Interestingly, TLR10 was found to be expressed at greater levels in IgM(+)IgD(+)CD27(+) compared with switched B cells in healthy patients. Hence, we propose a role for TIRAP-dependent TLRs, possibly TLR10 in particular, in the development and/or maintenance of IgM(+)IgD(+)CD27(+) B cells in humans.

Monitoring honeybee venom immunotherapy in children with the basophil activation test.

BACKGROUND: New in vitro methods are essential for developing better follow-up criteria for venom immunotherapy (VIT). METHODS: Thirty-one children with a history of honeybee venom-induced systemic anaphylaxis were included in this prospective, single-blinded study. The basophil CD63 activation test (BAT) was assessed before starting VIT, at the end of the build-up phase (day 5), 6 months later, and after 2-4 yr of VIT. RESULTS: Basophil CD63 activation test allowed identification of the culprit insect in 74% of honeybee venom-allergic children. In comparison, IgE reactivity was single positive in only 52% of children. Five days after starting VIT, BAT was highly comparable to before VIT. However, after 6 months and further after 2-4 yr of VIT, a significant and approximately fourfold decrease was demonstrated in CD63 response at sub-maximal 0.1 µg/ml allergen concentration, which mainly represents cellular sensitivity. No such differences were found at a higher 1 µg/ml of allergen concentration. Person-to-person analyses showed that after 2-4 yr of VIT, a marked CD63 decrease was evident in 85% of children. In addition, elevated basophil sensitivity measured before VIT was associated with the appearance of side effects observed during the build-up phase of VIT. CONCLUSION: Basophil CD63 allergen-specific sensitivity seems to be a promising tool for monitoring protective immune response in honeybee VIT.

Drowning--a scientometric analysis and data acquisition of a constant global problem employing density equalizing mapping and scientometric benchmarking procedures.

BACKGROUND: Drowning is a constant global problem which claims approximately half a million victims worldwide each year, whereas the number of near-drowning victims is considerably higher. Public health strategies to reduce the burden of death are still limited. While research activities in the subject drowning grow constantly, yet there is no scientometric evaluation of the existing literature at the present time. METHODS: The current study uses classical bibliometric tools and visualizing techniques such as density equalizing mapping to analyse and evaluate the scientific research in the field of drowning. The interpretation of the achieved results is also implemented in the context of the data collection of the WHO. RESULTS: All studies related to drowning and listed in the ISI-Web of Science database since 1900 were identified using the search term "drowning". Implementing bibliometric methods, a constant increase in quantitative markers such as number of publications per state, publication language or collaborations as well as qualitative markers such as citations were observed for research in the field of drowning. The combination with density equalizing mapping exposed different global patterns for research productivity and the total number of drowning deaths and drowning rates respectively. Chart techniques were used to illustrate bi- and multilateral research cooperation. CONCLUSIONS: The present study provides the first scientometric approach that visualizes research activity on the subject of drowning. It can be assumed that the scientific approach to this topic will achieve even greater dimensions because of its continuing actuality.

Clinical features and outcome of patients with IRAK-4 and MyD88 deficiency.

Autosomal recessive interleukin-1 receptor-associated kinase (IRAK)-4 and myeloid differentiation factor (MyD)88 deficiencies impair Toll-like receptor (TLR)- and interleukin-1 receptor-mediated immunity. We documented the clinical features and outcome of 48 patients with IRAK-4 deficiency and 12 patients with MyD88 deficiency, from 37 kindreds in 15 countries.The clinical features of IRAK-4 and MyD88 deficiency were indistinguishable. There were no severe viral, parasitic, and fungal diseases, and the range of bacterial infections was narrow. Noninvasive bacterial infections occurred in 52 patients, with a high incidence of infections of the upper respiratory tract and the skin, mostly caused by Pseudomonas aeruginosa and Staphylococcus aureus, respectively. The leading threat was invasive pneumococcal disease, documented in 41 patients (68%) and causing 72 documented invasive infections (52.2%). P. aeruginosa and Staph. aureus documented invasive infections also occurred (16.7% and 16%, respectively, in 13 and 13 patients, respectively). Systemic signs of inflammation were usually weak or delayed. The first invasive infection occurred before the age of 2 years in 53 (88.3%) and in the neonatal period in 19 (32.7%) patients. Multiple or recurrent invasive infections were observed in most survivors (n = 36/50, 72%).Clinical outcome was poor, with 24 deaths, in 10 cases during the first invasive episode and in 16 cases of invasive pneumococcal disease. However, no death and invasive infectious disease were reported in patients after the age of 8 years and 14 years, respectively. Antibiotic prophylaxis (n = 34), antipneumococcal vaccination (n = 31), and/or IgG infusion (n = 19), when instituted, had a beneficial impact on patients until the teenage years, with no seemingly detectable impact thereafter.IRAK-4 and MyD88 deficiencies predispose patients to recurrent life-threatening bacterial diseases, such as invasive pneumococcal disease in particular, in infancy and early childhood, with weak signs of inflammation. Patients and families should be informed of the risk of developing life-threatening infections; empiric antibacterial treatment and immediate medical consultation are strongly recommended in cases of suspected infection or moderate fever. Prophylactic measures in childhood are beneficial, until spontaneous improvement occurs in adolescence.

Association of Filaggrin loss-of-function-mutations with atopic dermatitis and asthma in the Early Treatment of the Atopic Child (ETAC) population.

Many candidate gene studies for atopic dermatitis (AD) and associated phenotypes have been conducted so far, but replication of significant results has been a major problem. Two loss of function polymorphisms FLG R501X- and 2282del4, in the Filaggrin (FLG) gene encoding for an epidermal barrier protein were recently identified. They were reported to be predisposing factors for AD and concomitant asthma. Several groups confirmed the initial results in independent populations. The aim of this study is to further investigate the importance of these FLG variants in the development of AD and subsequent asthma symptoms in pre-school children, we investigated children and parents of the Early Treatment of the Atopic Child (ETAC)-trial. We genotyped 496 children and 488 parents of the ETAC population for the two FLG variants, evaluating an association by family based analysis (transmission disequilibrium test). We found a highly significant association of the FLG null variants R501X- and 2282del4 with AD (combined genotype p < 0.0001) and asthma (combined genotype p < 0.0001). The replication and its statistical significance underlines the importance of the FLG polymorphisms and the importance of the skin barrier function in the development of AD and subsequent asthma.

IL13 variants are associated with total serum IgE and early sensitization to food allergens in children with atopic dermatitis.

Increased total and specific serum immunoglobulin E (IgE) levels are common characteristics of atopic diseases and their basal production is proposed to be under strong genetic control. Interleukin 13 (IL13) variants have been consistently associated with total serum IgE levels in white populations with a strongest association in non-atopics. The aim of this study was to test the IL13 p.R130Q and c.1-1111C>T variants in children with atopic dermatitis (AD) for associations with total serum IgE and early sensitization to common food and inhalant allergens and with asthma. We included 453 children with AD [participants of the Early Treatment of the Atopic Child (ETAC) study] that were followed from the age of 12-24 months for 3 yr. Total and specific IgE were determined at four time points. We genotyped the IL13 p.R130Q and c.1-1111C>T variants by melting curve analysis. In children up to 4 yr of age, the 130Q allele was related to slightly higher total IgE levels compared to heterozygotes and 130R homozygotes. More importantly, both IL13 variants were significantly associated with sensitization to food allergens, with most significant results for sensitization to egg (p = 0.0001). Although early sensitization to hen's egg represents a strong risk factor for subsequent sensitization to inhalant allergens and asthma, the investigated IL13 variants were not associated with these phenotypes at the age of 48-60 months. In summary IL13 variants contribute to elevated levels of total serum IgE in young atopic children and are strongly associated with sensitization to food allergens, particularly to hen's egg. These findings suggest that IL13 variants play a major role not only in non-cognate but also in allergen specific IgE synthesis.

Mutations in STAT3 and IL12RB1 impair the development of human IL-17-producing T cells.

The cytokines controlling the development of human interleukin (IL) 17--producing T helper cells in vitro have been difficult to identify. We addressed the question of the development of human IL-17--producing T helper cells in vivo by quantifying the production and secretion of IL-17 by fresh T cells ex vivo, and by T cell blasts expanded in vitro from patients with particular genetic traits affecting transforming growth factor (TGF) beta, IL-1, IL-6, or IL-23 responses. Activating mutations in TGFB1, TGFBR1, and TGFBR2 (Camurati-Engelmann disease and Marfan-like syndromes) and loss-of-function mutations in IRAK4 and MYD88 (Mendelian predisposition to pyogenic bacterial infections) had no detectable impact. In contrast, dominant-negative mutations in STAT3 (autosomal-dominant hyperimmunoglobulin E syndrome) and, to a lesser extent, null mutations in IL12B and IL12RB1 (Mendelian susceptibility to mycobacterial diseases) impaired the development of IL-17--producing T cells. These data suggest that IL-12Rbeta1- and STAT-3--dependent signals play a key role in the differentiation and/or expansion of human IL-17-producing T cell populations in vivo.

MBL2 variants in relation to common childhood infections and atopy-related phenotypes in a large German birth cohort.

Mannose-binding lectin (MBL) is considered an important component of innate immunity. Four functional MBL2 alterations in codons 52, 54, 57 and in the promoter at position c.1-290 are correlated with significantly lowered MBL serum levels. These variants have been associated with susceptibility to a variety of infectious agents as well as with various immunologic disorders including asthma. To reassess these observations, we analysed the four above mentioned MBL2 variants in 749 children, who were recruited by the German Multicenter Allergy Study and were prospectively evaluated for common respiratory childhood infections and atopy-related phenotypes from birth up to the age of 11 yr. We performed genotyping by melting curve analysis using fluorescence resonance energy transfer probes and the LightCycler. In contrast to previous studies, we found an association of MBL2 variants neither with the frequency of common respiratory childhood infections at any age nor with asthma or other atopy-related phenotypes. Our data suggest that MBL deficiency does not represent a pre-disposing factor for respiratory infections or atopic disorders in infants and children.