Search Engine Use for Health-Related Purposes: Behavioral Data on Online Health Information-Seeking in Germany.

Internet searches for health-related purposes are common, with search engines like Google being the most popular starting point. However, results on the popularity of health information-seeking behaviors are based on self-report data, often criticized for suffering from incomplete recall, overreporting, and low reliability. Therefore, the current study builds on user-centric tracking of Internet use to reveal how individuals actually behave online. We conducted a secondary analysis of passively recorded Internet use logs to examine the prevalence of health-related search engine use, the types of health information searched for, and the sources visited after the searches. The analysis revealed two key findings. 1) We largely support earlier survey-based findings on the prevalence of online health information seeking with search engines and the relatively minor differences in information-seeking behaviors between socio-demographic groups. 2) We provide a more granular picture of the process of HISB using search engines by identifying different selection patterns depending on the scope of the searches.

A Short Scale to Measure Self-Reported Aversive Personality in Political Elites.

In order to explain the behavior of political elites, research increasingly considers personality traits. Within this line of research, a recent focus is on socially aversive - yet non-pathological - personality traits (e.g., Machiavellianism, narcissism, psychopathy), with the idea to better understand behavior violating generally accepted ethical, moral, and social norms. Assessments of politicians' aversive personality traits have so far been almost exclusively based on observer reports of experts and voters. Herein, by contrast, we introduce the Political Elites Aversive Personality Scale ("PEAPS") particularly tailored to measure self-reported aversive personality among politicians. More precisely, based on two studies with German politicians, we develop a 6-item short scale comprising aspects of different socially aversive personality traits (Machiavellianism, narcissism, psychopathy, and spitefulness). The scale shows an acceptable model fit, an acceptable internal consistency, an acceptable measurement equivalence, and meaningful correlations with other (self-reported) psychological traits and campaign behavior. Moreover, the scale significantly contributes to the explanation of candidates' negative campaigning, going beyond the explanatory power of models capturing broad, basic personality traits. Overall, the suggested scale provides interesting links to research in (political) psychology and can help to explain attitudes, behavior, and performance of political elites.

Variation in the calpain-10 gene is not associated with gestational diabetes mellitus.

BACKGROUND: In several large studies an association between certain single-nucleotide polymorphisms (SNP) of the calpain-10 gene (CAPN10) with type 2 diabetes mellitus (T2D) has been identified. Since T2D and gestational diabetes mellitus (GDM) seem to be linked pathophysiologically, we examined the frequencies of CAPN10-polymorphisms in women with GDM. METHODS: By using real-time PCR assisted melting curve analysis samples of 204 women with GDM and 297 controls were tested for variations of SNP-43, -44, -63 and Indel-19 of CAPN10. RESULTS: Since the genotype frequencies found in SNP-44 among the controls did not meet the Hardy-Weinberg-Equilibrium, the further analysis was performed with SNP-43, -63 and Indel-19 only. Herein, the distribution of neither genotype nor allele nor haplogenotype-combination nor haplotype showed a significant difference between both groups. CONCLUSIONS: Variations of SNP-43, -63 and Indel-19 of CAPN10 were not associated with an increased risk of developing GDM.

Successful treatment of intractable hiccups by oral application of lidocaine.

BACKGROUND: Persistent and intractable hiccups are a rather rare, but distressing gastrointestinal symptom found in palliative care patients. Although several recommendations for treatment are given, hiccups often persist. CASE REPORTS: We describe a new pharmacological approach for successfully treating hiccups in four cancer patients. In the first patient, chronic and intractable hiccups lasted for more than 18 months, but disappeared immediately after swallowing a viscous 2 % lidocaine solution for treatment of mucositis. Based on this experience, we successfully treated three further patients suffering from singultus using a lidocaine-containing gel. To our knowledge, this is the first report about managing hiccups by oral application of a lidocaine solution.

Coordination patterns reveal online political astroturfing across the world.

Online political astroturfing-hidden information campaigns in which a political actor mimics genuine citizen behavior by incentivizing agents to spread information online-has become prevalent on social media. Such inauthentic information campaigns threaten to undermine the Internet's promise to more equitable participation in public debates. We argue that the logic of social behavior within the campaign bureaucracy and principal-agent problems lead to detectable activity patterns among the campaign's social media accounts. Our analysis uses a network-based methodology to identify such coordination patterns in all campaigns contained in the largest publicly available database on astroturfing published by Twitter. On average, 74% of the involved accounts in each campaign engaged in a simple form of coordination that we call co-tweeting and co-retweeting. Comparing the astroturfing accounts to various systematically constructed comparison samples, we show that the same behavior is negligible among the accounts of regular users that the campaigns try to mimic. As its main substantive contribution, the paper demonstrates that online political astroturfing consistently leaves similar traces of coordination, even across diverse political and country contexts and different time periods. The presented methodology is a reliable first step for detecting astroturfing campaigns.

Osteopontin is a hematopoietic stem cell niche component that negatively regulates stem cell pool size.

Stem cells reside in a specialized niche that regulates their abundance and fate. Components of the niche have generally been defined in terms of cells and signaling pathways. We define a role for a matrix glycoprotein, osteopontin (OPN), as a constraining factor on hematopoietic stem cells within the bone marrow microenvironment. Osteoblasts that participate in the niche produce varying amounts of OPN in response to stimulation. Using studies that combine OPN-deficient mice and exogenous OPN, we demonstrate that OPN modifies primitive hematopoietic cell number and function in a stem cell-nonautonomous manner. The OPN-null microenvironment was sufficient to increase the number of stem cells associated with increased stromal Jagged1 and Angiopoietin-1 expression and reduced primitive hematopoietic cell apoptosis. The activation of the stem cell microenvironment with parathyroid hormone induced a superphysiologic increase in stem cells in the absence of OPN. Therefore, OPN is a negative regulatory element of the stem cell niche that limits the size of the stem cell pool and may provide a mechanism for restricting excess stem cell expansion under conditions of niche stimulation.

Energetic Profile of the Basketball Exercise Simulation Test in Junior Elite Players.

PURPOSE: To analyze the energetic profile of the Basketball Exercise Simulation Test (BEST). METHODS: Ten male elite junior basketball players (age 15.5 [0.6] y, height 180 [9] cm, and body mass 66.1 [11.2] kg) performed a modified BEST (20 circuits consisting of jumping, sprinting, jogging, shuffling, and short breaks) simulating professional basketball game play. Circuit time, sprint time, sprint decrement, oxygen uptake (VO2), heart rate, and blood lactate concentration (blc) were obtained. Metabolic energy and metabolic power above rest (Wtot and Ptot), as well as energy share in terms of aerobic (Waer), glycolytic (Wblc), and high-energy phosphates (WPCr), were calculated from VO2 during exercise, net lactate production, and the fast component of postexercise VO2 kinetics, respectively. RESULTS: Waer, Wblc, and WPCr reflect 89% (2%), 5% (1%), and 6% (1%) of total energy needed, respectively. Assuming an aerobic replenishment of PCr energy stores during short breaks, the adjusted energy share yielded Waer 66% (4%), Wblc 5% (1%), and WPCr 29% (1%). Waer and WPCr were negatively correlated (-0.72 and -0.59) with sprint time, which was not the case for Wblc. CONCLUSIONS: Consistent with general findings on energy system interaction during repeated high-intensity exercise bouts, the intermittent profile of the BEST relies primarily on aerobic energy combined with repetitive supplementation by anaerobic utilization of high-energy phosphates.

A phase I/II trial of topotecan and radiation therapy for brain metastases in patients with solid tumors.

PURPOSE: Outcomes in patients with brain metastases undergoing whole-brain radiotherapy (WBRT) are hardly encouraging, and an improvement in results is therefore needed. One possible approach is the addition of chemotherapeutics. However the data presented thus far are also disappointing. A promising substance in this setting could become topotecan, which is known to cross the blood-brain barrier and additionally offers radiosensitizing effects. Therefore we performed a phase I/II trial to evaluate the feasibility of a concurrent radiochemotherapy regimen. METHODS AND MATERIALS: From January 1999 to July 2001, a total of 75 patients (10 in phase I and 65 in phase II) were included. The WBRT was applied with a fraction size of 2 Gy/day for a total of 40 Gy. Topotecan was administered as a 30-min infusion with 0.2 to 0.5 mg/m(2)/day for 5 days over 4 weeks within 2 h to radiation therapy. RESULTS: Because of the higher toxic rates seen in patients receiving 0.5 mg/m(2)/day, the recommended dosage for phase II was 0.4 mg/m(2)/day. In this group Grade 3/4 hematologic and nonhematologic side effects occurred in 19% and 21% of the patients, respectively. The overall response rate was 72% with an overall survival of 17 weeks and 30 weeks among the responders. CONCLUSIONS: Based on the moderate toxicity profile presented here we recommend to perform a phase III trial to confirm the promising phase I/II data.

Hodgkin's lymphoma in a patient with Jo-1 syndrome.

Jo-1 syndrome is an autoimmune disease with autoantibodies against the histidyl tRNA synthetase. Characteristic clinical findings include inflammatory myopathy and interstitial lung disease. We present the first case of a patient with Jo-1 syndrome (positive Jo-1 autoantibodies, myositis, interstitial alveolitis) who developed Hodgkin's lymphoma of nodular-sclerosing type. Thus, patients with Jo-1 syndrome and immunosuppressive therapy similar to other patients with autoimmune disease are at risk to develop lymphomas and should therefore be monitored carefully.

Identification of p54(nrb) and the 14-3-3 Protein HS1 as TNF-alpha-inducible genes related to cell cycle control and apoptosis in human arterial endothelial cells.

TNF-alpha plays a pivotal role in inflammation processes which are mainly regulated by endothelial cells. While TNF-alpha induces apoptosis of several cell types like tumor cells, endothelial cells are resistant to TNFa mediated cell death. The cytotoxic effects of TNF-alpha on most cells are only evident if RNA or protein synthesis is inhibited, suggesting that de novo RNA or protein synthesis protect cells from TNF-alpha cytotoxicity, presumably by NF-kappaB mediated induction of protective genes. However, the cytoprotective genes involved in NF-kappaB dependent endothelial cell survival have not been sufficiently identified. In the present study, the suppression subtractive hybridization (SSH) method was employed to identify rarely transcribed TNF-alpha inducible genes in human arterial endothelial cells related to cell survival and cell cycle. The TNF-alpha-induced expression of the RNA binding protein p54(nrb) and the 14-3-3 protein HS1 as shown here for the first time may contribute to the TNF-alpha mediated cell protection of endothelial cells. These genes have been shown to play pivotal roles in cell survival and cell cycle control in different experimental settings. The concerted expression of these genes together with other genes related to cell protection and cell cycle like DnaJ, p21(cip1) and the ubiquitin activating enzyme E1 demonstrates the identification of new genes in the context of TNF-alpha induced gene expression patterns mediating the prosurvival effect of TNF-alpha in endothelial cells.

Stromal cell-derived factor 1alpha (SDF-1alpha) induces gene-expression of early growth response-1 (Egr-1) and VEGF in human arterial endothelial cells and enhances VEGF induced cell proliferation.

Stromal cell-derived factor-1 (SDF-1), mainly known as a chemotactic factor for haematopoietic progenitor cells, also provides angiogenetic potency. Since the intracellular signalling of SDF-1-induced neovascularization remains unclear, we studied in human umbilical arterial endothelial cells (HUAEC) the influence of SDF-1alpha on induction of the genes of early growth response-1 (Egr-1) and VEGF, as well as the activation of extracellular regulated kinases (ERK) 1/2, which are all known to be involved in endothelial cell proliferation. We found a time-dependent induction of Egr-1 and VEGF mRNA expression and phosphorylation of ERK1/2 by SDF-1alpha. Furthermore, we demonstrated that Egr-1 expression is dependent on ERK 1/2 activation. Finally, we tried to confirm the relevance of the induced gene expression by detecting the [3H]thymidine incorporation as a marker for cell proliferation in HUAEC after stimulation with SDF-1alpha alone or together with VEGF. This particular test showed, that SDF-1alpha alone has no effect, but is able to significantly enhance VEGF induced DNA synthesis. In summary, SDF-1alpha is involved in different steps of endothelial cell proliferation, but, since Egr-1 and VEGF offer different functions, it may also play a so far undefined role on other conditions of the endothelium.

Inhibition of the vascular-endothelial growth factor-induced intracellular signaling and mitogenesis of human endothelial cells by epigallocatechin-3 gallate.

Galloyl group-containing catechins, such as epigallocatechin-3 gallate, inhibit receptor tyrosine kinase activity of several growth factor receptors. This study investigated the effects of epigallocatechin-3 gallate, as compared to epicatechin, on vascular endothelial growth factor-induced intracellular signaling and mitogenesis of human umbilical endothelial cells. Epigallocatechin-3 gallate concentration-dependently inhibited vascular endothelial growth factor-induced DNA synthesis, cell proliferation, autophosphorylation of vascular endothelial growth factor receptors-1 and -2, phosphorylation of extracellular signal-regulated kinases-1 and -2, and mRNA expression of the early growth response factor-1. In contrast, epicatechin was not effective. Thus, epigallocatechin-3 gallate may be an attractive candidate drug to inhibit tumour angiogenesis.

Discontinuation of the tyrosine kinase inhibitor sunitinib in patients with metastatic renal cell carcinoma: a case series.

PURPOSE: Tyrosine kinase inhibitors (TKI) play a pivotal role in the modern treatment of patients with metastatic renal cell carcinoma (mRCC). Depending on the course and the response, the targeted therapy may last for years. Thus the question arises, if a successful treatment leading to a complete response or at least a stable disease after a partial remission, may be discontinued. MATERIALS AND METHODS: Here we present 3 patients with mRCC treated with sunitinib for at least one year, resulting in a partial response, followed by a stable disease for several years. In these patients, the treatment was interrupted for different medical reasons. RESULTS: After a period of 20, 33 and 34 months, respectively, the metastases of the renal cell cancer showed no signs of progression, neither clinically nor in computed tomography scans, but the side effects of TKI or the medical problem leading to treatment interruption resolved in all patients within a few weeks. CONCLUSION: The discontinuation of the treatment for mRCC with TKI seems to be possible, even in those patients with a partial response only, but no complete remission has been achieved before.

Effects of ezetimibe and/or simvastatin on LDL receptor protein expression and on LDL receptor and HMG-CoA reductase gene expression: a randomized trial in healthy men.

OBJECTIVE: The combination of simvastatin, an HMG-CoA reductase inhibitor, and ezetimibe, an inhibitor of Niemann-Pick C1-like 1 protein, decreases cholesterol synthesis and absorption and reduces circulating LDL-cholesterol concentrations. The molecular mechanisms underlying the pronounced lipid-lowering effects of this combination have not been fully elucidated in humans. METHODS AND RESULTS: One center, prospective, randomized, parallel three-group study in 72 healthy men (mean age 32+/-9 years, mean body mass index 25.7+/-3.2 kg/m(2)). Each group of twenty-four subjects received a 14-day treatment with either ezetimibe (10mg/day), simvastatin (40 mg/day) or their combination. Lipid levels, the ratio of non-cholesterol sterols to cholesterol concentrations (used as markers of cholesterol synthesis and absorption), cell surface LDL receptor (LDLR) protein as well as LDLR and HMG-CoA reductase gene expression in mononuclear blood cells were measured at baseline and at the end of the study. LDL-C decreased in all groups. Simvastatin decreased, ezetimibe increased and their combination had no effect on HMG-CoA reductase activity. Simvastatin and the combination of ezetimibe and simvastatin increased the HMG-CoA reductase and LDLR gene expression while ezetimibe had no effect. The cell surface LDLR protein expression remained unchanged in all groups. The combination of ezetimibe and simvastatin increased the expression of the serine protease proprotein convertase subtilisin/kexin 9 (PCSK9), an enzyme shown to down-regulate LDLR protein levels. CONCLUSIONS: The co-administration of ezetimibe and simvastatin abrogates the ezetimibe-induced increase in cholesterol synthesis and up-regulates the LDLR gene but not protein expression, an effect possibly mediated through a parallel upregulation of PCSK9 expression.

Loss of imprinting of the insulin-like growth factor 2 and the H19 gene in testicular seminomas detected by real-time PCR approach.

IGF2 and H19 are imprinted genes in normal human tissue, but many studies have observed a loss of imprinting (LOI) of these genes in tumors as an epigenetic alteration of the DNA, that leads to a biallelic expression predisposing cells to carcinogenesis and tumor growth. The aim of this study was to test the reliability of LightCycler-assisted Real-time PCR in detecting LOI of IGF2 and H19 in 39 patients with testicular germ cell tumors by comparing these results with the analysis generated by the golden standard restriction fragment length polymorphism (RFLP). With LightCycler-assisted Real-time PCR for IGF2 44% and for H19 49% of the patients were found to be heterozygous. This was consistent with the results obtained by RFLP, but surprisingly RFLP failed in more than 7% of the patients. In detecting LOI (for IGF2 in 41% and for H19 in 68% of the informative patients) the approach by RFLP was superior, since the results derived from LightCycler-assisted Real-time PCR showed reliable results in 76 and 10% of the samples concerning IGF2 and H19, respectively. Again, no discrepancy between the results obtained by the two methods occurred. In sum, LightCycler-assisted Real-time PCR is a sufficiently working approach for the rapid and reliable detection of heterozygosity of IGF2 or H19 gene and identification of LOI of IGF2 and thus may be helpful in conducting large epidemiological studies. However, for the identification of LOI of the H19 gene in this cohort it possesses only restrictive use.

Role of exposure to radon and silicosis on the cell type of lung carcinoma in German uranium miners.

BACKGROUND: In East Germany, uranium mining was undertaken on a large scale from 1946 to 1990. Poor working conditions led to a high level of exposure to ionizing radiation and quartz dust. This analysis evaluates the histopathology of lung carcinoma in uranium miners in relation to radon exposure and silicosis. METHODS: A database developed for autopsy cases ascertained in a pathological tissue repository of German uranium miners was used to estimate odds ratios for developing lung carcinoma by major cell type with regard to radon exposure and silicosis. Silicosis information was extracted from autopsy protocols. Working level months (WLM) were calculated with a job-exposure matrix to assess lifetime radon exposure. Risk estimates were based on 3414 male miners who died from small cell lung carcinoma (SCLC, n = 1446), squamous cell carcinoma (SqCC, n = 1006), or adenocarcinoma (AC, n = 962) between 1957 and 1990. RESULTS: SCLC and SqCC seem more likely to be associated with high radon exposure than AC. Mean cumulative radon exposure was 868 (SD 631) WLM in SCLC, 871 (SD 652) WLM in SqCC, and 743 (SD 598) WLM in AC. Silicosis prevalence was 26% in SCLC, 38% in SqCC, and 30% in AC. In silicotics, AC and SqCC had a relatively higher frequency at the expense of SCLC. SCLC occurred earlier than AC and SqCC. CONCLUSION: High radon exposure was associated with a higher relative frequency of SCLC and SqCC than AC. Silicosis tended to increase the appearance of SqCC and AC.

Gemcitabine and paclitaxel in metastatic or recurrent squamous cell carcinoma of the head and neck: a phase I-II study.

The purpose of this study was to determine the maximum tolerated dose, toxicity profile and anti-tumor activity of paclitaxel in combination with gemcitabine when administered to patients with unresectable locally recurrent or metastatic squamous cell carcinoma of the head and the neck (SCCHN). Twenty-seven patients were treated in a phase I-II study with gemcitabine at a dose of 800 mg/m on days 1 and 8, escalating to a dose of 1,000 mg/m, plus escalating doses of paclitaxel (100, 135 and 175 mg/m) on day 2. Treatment consisted of 6 cycles repeated every 3 weeks. The main toxicity was myelosuppression. Other toxicities were mild and manageable. Due to grade 4 neutropenia at higher doses the recommended dose level of the gemcitabine/paclitaxel combination was 1,000/135 mg/m. Four patients achieved a partial response and no patient had a complete remission, giving an overall response rate of 14.8%. The median time of survival was 24 weeks. We conclude that the combination of paclitaxel and gemcitabine is tolerated, but shows insufficient clinical activity in patients with recurrent and/or metastatic SCCHN to warrant further testing.

The vast majority of bone-marrow-derived cells integrated into mdx muscle fibers are silent despite long-term engraftment.

Bone-marrow-derived cells can contribute nuclei to skeletal muscle fibers. However, serial sectioning of muscle in mdx mice implanted with GFP-labeled bone marrow reveals that only 20% of the donor nuclei chronically incorporated in muscle fibers show dystrophin (or GFP) expression, which is still higher than the expected frequency of "revertant" fibers, but there is no overall increase above controls over time. Obviously, the vast majority of incorporated nuclei either never or only temporarily turn on myogenic genes; also, incorporated nuclei eventually loose the activation of the beta-actin::GFP transgene. Consequently, we attempted to enhance the expression of dystrophin. In vivo application of the chromatin-modifying agents 5-azadeoxycytidine and phenylbutyrate as well as local damage by cardiotoxin injections caused a small increase in dystrophin-positive fibers without abolishing the appearance of "silent" nuclei. The results thus confirm that endogenous repair processes and epigenetic modifications on a small-scale lead to dystrophin expression from donor nuclei. Both effects, however, remain below functionally significant levels.

Notch1 activation increases hematopoietic stem cell self-renewal in vivo and favors lymphoid over myeloid lineage outcome.

Hematopoietic stem cells sequentially pass through a series of decision points affecting self-renewal or lineage-specific differentiation. Notch1 receptor is a known modulator of lineage-specific events in hematopoiesis that we assessed in the context of in vivo stem cell kinetics. Using RAG-1(-/-) mouse stems cells, we documented increased stem cell numbers due to decreased differentiation and enhanced stem cell self-renewal induced by Notch1. Unexpectedly, preferential lymphoid over myeloid lineage commitment was noted when differentiation occurred. Therefore, Notch1 affects 2 decision points in stem cell regulation, favoring self-renewal over differentiation and lymphoid over myeloid lineage outcome. Notch1 offers an attractive target for stem cell manipulation strategies, particularly in the context of immunodeficiency and acquired immunodeficiency syndrome.