The impact of a low-frequency chlorhexidine rinsing schedule on the subgingival microbiota (the TEETH clinical trial)

BACKGROUND: Information on the efficacy of chlorhexidine (CHX) rinsing on the subgingival microbiota is limited. This study tested if intermittent CHX rinsing over 5 years had an impact on the subgingival microbiota. METHODS: Subgingival plaque samples were analyzed by the checkerboard DNA-DNA hybridization method in a double-blind randomized CHX rinse study. RESULTS: A total of 210 subjects were included. The mean age of the subjects was 71.7 (+/- 4.1) years, and 56.2% were women. Evidence of alveolar bone loss was found in 39% of subjects. Bacterial loads were not correlated significantly with probing depth. At year 5, subjects in the CHX rinse group with no evidence of bone loss presented with lower total bacterial counts than control subjects with no bone loss. The levels of the following bacteria were significantly lower in the CHX group: Lactobacillus acidophilus (P <0.05), Eikenella corrodens (P <0.05), Fusobacterium nucleatum sp. nucleatum (P <0.01), Treponema denticola (P <0.05), Leptotrichia buccalis (P <0.05), and Eubacterium saburreum (P <0.05). No differences in bacterial loads were found between CHX and control rinse subjects with alveolar bone loss. CONCLUSIONS: Older subjects with or without periodontitis carry a large variety of bacteria associated with periodontitis. Intermittent rinsing with CHX may provide a preventive benefit in reducing levels of bacteria but only in subjects without alveolar bone loss.

Cardiovascular mortality and exposure to extremely low frequency magnetic fields: a cohort study of Swiss railway workers

BACKGROUND: Exposure to intermittent magnetic fields of 16 Hz has been shown to reduce heart rate variability, and decreased heart rate variability predicts cardiovascular mortality. We examined mortality from cardiovascular causes in railway workers exposed to varying degrees to intermittent 16.7 Hz magnetic fields. METHODS: We studied a cohort of 20,141 Swiss railway employees between 1972 and 2002, including highly exposed train drivers (median lifetime exposure 120.5 muT-years), and less or little exposed shunting yard engineers (42.1 muT-years), train attendants (13.3 muT-years) and station masters (5.7 muT-years). During 464,129 person-years of follow up, 5,413 deaths were recorded and 3,594 deaths were attributed to cardio-vascular diseases. We analyzed data using Cox proportional hazards models. RESULTS: For all cardiovascular mortality the hazard ratio compared to station masters was 0.99 (95%CI: 0.91, 1.08) in train drivers, 1.13 (95%CI: 0.98, 1.30) in shunting yard engineers, and 1.09 (95%CI: 1.00, 1.19) in train attendants. Corresponding hazard ratios for arrhythmia related deaths were 1.04 (95%CI: 0.68, 1.59), 0.58 (95%CI: 0.24, 1.37) and 10 (95%CI: 0.87, 1.93) and for acute myocardial infarction 1.00 (95%CI: 0.73, 1.36), 1.56 (95%CI: 1.04, 2.32), and 1.14 (95%CI: 0.85, 1.53). The hazard ratio for arrhythmia related deaths per 100 muT-years of cumulative exposure was 0.94 (95%CI: 0.71, 1.24) and 0.91 (95%CI: 0.75, 1.11) for acute myocardial infarction. CONCLUSION: This study provides evidence against an association between long-term occupational exposure to intermittent 16.7 Hz magnetic fields and cardiovascular mortality.

Temporal and spatial variability of personal exposure to radio frequency electromagnetic fields

BACKGROUND: Little is known about the population's exposure to radio frequency electromagnetic fields (RF-EMF) in industrialized countries. OBJECTIVES: To examine levels of exposure and the importance of different RF-EMF sources and settings in a sample of volunteers living in a Swiss city. METHODS: RF-EMF exposure of 166 volunteers from Basel, Switzerland, was measured with personal exposure meters (exposimeters). Participants carried an exposimeter for 1 week (two separate weeks in 32 participants) and completed an activity diary. Mean values were calculated using the robust regression on order statistics (ROS) method. RESULTS: Mean weekly exposure to all RF-EMF sources was 0.13 mW/m(2) (0.22 V/m) (range of individual means 0.014-0.881 mW/m(2)). Exposure was mainly due to mobile phone base stations (32.0%), mobile phone handsets (29.1%) and digital enhanced cordless telecommunications (DECT) phones (22.7%). Persons owning a DECT phone (total mean 0.15 mW/m(2)) or mobile phone (0.14 mW/m(2)) were exposed more than those not owning a DECT or mobile phone (0.10 mW/m(2)). Mean values were highest in trains (1.16 mW/m(2)), airports (0.74 mW/m(2)) and tramways or buses (0.36 mW/m(2)), and higher during daytime (0.16 mW/m(2)) than nighttime (0.08 mW/m(2)). The Spearman correlation coefficient between mean exposure in the first and second week was 0.61. CONCLUSIONS: Exposure to RF-EMF varied considerably between persons and locations but was fairly consistent within persons. Mobile phone handsets, mobile phone base stations and cordless phones were important sources of exposure in urban Switzerland.

A prediction model for personal radio frequency electromagnetic field exposure

Radio frequency electromagnetic fields (RF-EMF) in our daily life are caused by numerous sources such as fixed site transmitters (e.g. mobile phone base stations) or indoor devices (e.g. cordless phones). The objective of this study was to develop a prediction model which can be used to predict mean RF-EMF exposure from different sources for a large study population in epidemiological research. We collected personal RF-EMF exposure measurements of 166 volunteers from Basel, Switzerland, by means of portable exposure meters, which were carried during one week. For a validation study we repeated exposure measurements of 31 study participants 21 weeks after the measurements of the first week on average. These second measurements were not used for the model development. We used two data sources as exposure predictors: 1) a questionnaire on potentially exposure relevant characteristics and behaviors and 2) modeled RF-EMF from fixed site transmitters (mobile phone base stations, broadcast transmitters) at the participants' place of residence using a geospatial propagation model. Relevant exposure predictors, which were identified by means of multiple regression analysis, were the modeled RF-EMF at the participants' home from the propagation model, housing characteristics, ownership of communication devices (wireless LAN, mobile and cordless phones) and behavioral aspects such as amount of time spent in public transports. The proportion of variance explained (R2) by the final model was 0.52. The analysis of the agreement between calculated and measured RF-EMF showed a sensitivity of 0.56 and a specificity of 0.95 (cut-off: 90th percentile). In the validation study, the sensitivity and specificity of the model were 0.67 and 0.96, respectively. We could demonstrate that it is feasible to model personal RF-EMF exposure. Most importantly, our validation study suggests that the model can be used to assess average exposure over several months.

Exposure to Radio-Frequency Electromagnetic Fields From Broadcast Transmitters and Risk of Childhood Cancer: A Census-based Cohort Study

We investigated the association between exposure to radio-frequency electromagnetic fields (RF-EMFs) from broadcast transmitters and childhood cancer. First, we conducted a time-to-event analysis including children under age 16 years living in Switzerland on December 5, 2000. Follow-up lasted until December 31, 2008. Second, all children living in Switzerland for some time between 1985 and 2008 were included in an incidence density cohort. RF-EMF exposure from broadcast transmitters was modeled. Based on 997 cancer cases, adjusted hazard ratios in the time-to-event analysis for the highest exposure category (>0.2 V/m) as compared with the reference category (<0.05 V/m) were 1.03 (95% confidence interval (CI): 0.74, 1.43) for all cancers, 0.55 (95% CI: 0.26, 1.19) for childhood leukemia, and 1.68 (95% CI: 0.98, 2.91) for childhood central nervous system (CNS) tumors. Results of the incidence density analysis, based on 4,246 cancer cases, were similar for all types of cancer and leukemia but did not indicate a CNS tumor risk (incidence rate ratio = 1.03, 95% CI: 0.73, 1.46). This large census-based cohort study did not suggest an association between predicted RF-EMF exposure from broadcasting and childhood leukemia. Results for CNS tumors were less consistent, but the most comprehensive analysis did not suggest an association.

Low-frequency drug-resistant HIV-1 and risk of virological failure to first-line NNRTI-based ART: a multicohort European case-control study using centralized ultrasensitive 454 pyrosequencing.

OBJECTIVES It is still debated if pre-existing minority drug-resistant HIV-1 variants (MVs) affect the virological outcomes of first-line NNRTI-containing ART. METHODS This Europe-wide case-control study included ART-naive subjects infected with drug-susceptible HIV-1 as revealed by population sequencing, who achieved virological suppression on first-line ART including one NNRTI. Cases experienced virological failure and controls were subjects from the same cohort whose viraemia remained suppressed at a matched time since initiation of ART. Blinded, centralized 454 pyrosequencing with parallel bioinformatic analysis in two laboratories was used to identify MVs in the 1%-25% frequency range. ORs of virological failure according to MV detection were estimated by logistic regression. RESULTS Two hundred and sixty samples (76 cases and 184 controls), mostly subtype B (73.5%), were used for the analysis. Identical MVs were detected in the two laboratories. 31.6% of cases and 16.8% of controls harboured pre-existing MVs. Detection of at least one MV versus no MVs was associated with an increased risk of virological failure (OR = 2.75, 95% CI = 1.35-5.60, P = 0.005); similar associations were observed for at least one MV versus no NRTI MVs (OR = 2.27, 95% CI = 0.76-6.77, P = 0.140) and at least one MV versus no NNRTI MVs (OR = 2.41, 95% CI = 1.12-5.18, P = 0.024). A dose-effect relationship between virological failure and mutational load was found. CONCLUSIONS Pre-existing MVs more than double the risk of virological failure to first-line NNRTI-based ART.

Disruption of right prefrontal cortex by low-frequency repetitive transcranial magnetic stimulation induces risk-taking behavior

Decisions require careful weighing of the risks and benefits associated with a choice. Some people need to be offered large rewards to balance even minimal risks, whereas others take great risks in the hope for an only minimal benefit. We show here that risk-taking is a modifiable behavior that depends on right hemisphere prefrontal activity. We used low-frequency, repetitive transcranial magnetic stimulation to transiently disrupt left or right dorsolateral prefrontal cortex (DLPFC) function before applying a well known gambling paradigm that provides a measure of decision-making under risk. Individuals displayed significantly riskier decision-making after disruption of the right, but not the left, DLPFC. Our findings suggest that the right DLPFC plays a crucial role in the suppression of superficially seductive options. This confirms the asymmetric role of the prefrontal cortex in decision-making and reveals that this fundamental human capacity can be manipulated in normal subjects through cortical stimulation. The ability to modify risk-taking behavior may be translated into therapeutic interventions for disorders such as drug abuse or pathological gambling.

8p23 beta-defensin copy number determination by single-locus pseudogene-based paralog ratio tests risk bias due to low-frequency sequence variations.

BACKGROUND The copy number variation (CNV) in beta-defensin genes (DEFB) on human chromosome 8p23 has been proposed to contribute to the phenotypic differences in inflammatory diseases. However, determination of exact DEFB CN is a major challenge in association studies. Quantitative real-time PCR (qPCR), paralog ratio tests (PRT) and multiplex ligation-dependent probe amplification (MLPA) have been extensively used to determine DEFB CN in different laboratories, but inter-method inconsistencies were observed frequently. In this study we asked which one is superior among the three methods for DEFB CN determination. RESULTS We developed a clustering approach for MLPA and PRT to statistically correlate data from a single experiment. Then we compared qPCR, a newly designed PRT and MLPA for DEFB CN determination in 285 DNA samples. We found MLPA had the best convergence and clustering results of the raw data and the highest call rate. In addition, the concordance rates between MLPA or PRT and qPCR (32.12% and 37.99%, respectively) were unacceptably low with underestimated CN by qPCR. Concordance rate between MLPA and PRT (90.52%) was high but PRT systematically underestimated CN by one in a subset of samples. In these samples a sequence variant which caused complete PCR dropout of the respective DEFB cluster copies was found in one primer binding site of one of the targeted paralogous pseudogenes. CONCLUSION MLPA is superior to PRT and even more to qPCR for DEFB CN determination. Although the applied PRT provides in most cases reliable results, such a test is particularly sensitive to low-frequency sequence variations preferably accumulating in loci like pseudogenes which are most likely not under selective pressure. In the light of the superior performance of multiplex assays, the drawbacks of such single PRTs could be overcome by combining more test markers.

Active immunosurveillance in the tumor microenvironment of colorectal cancer is associated with low frequency tumor budding and improved outcome.

Tumor budding (single tumor cells or small tumor cell clusters) at the invasion front of colorectal cancer (CRC) is an adverse prognostic indicator linked to epithelial-mesenchymal transition. This study characterized the immunogenicity of tumor buds by analyzing the expression of the major histocompatibility complex (MHC) class I in the invasive tumor cell compartment. We hypothesized that maintenance of a functional MHC-I antigen presentation pathway, activation of CD8+ T-cells, and release of antitumoral effector molecules such as cytotoxic granule-associated RNA binding protein (TIA1) in the tumor microenvironment can counter tumor budding and favor prolonged patient outcome. Therefore, a well-characterized multipunch tissue microarray of 220 CRCs was profiled for MHC-I, CD8, and TIA1 by immunohistochemistry. Topographic expression analysis of MHC-I was performed using whole tissue sections (n = 100). Kirsten rat sarcoma viral oncogene homolog (KRAS) and B-Raf proto-oncogene, serine/threonine kinase (BRAF) mutations, mismatch repair (MMR) protein expression, and CpG-island methylator phenotype (CIMP) were investigated. Our results demonstrated that membranous MHC-I expression is frequently down-regulated in the process of invasion. Maintained MHC-I at the invasion front strongly predicted low-grade tumor budding (P = 0.0004). Triple-positive MHC-I/CD8/TIA1 in the tumor microenvironment predicted early T-stage (P = 0.0031), absence of lymph node metastasis (P = 0.0348), lymphatic (P = 0.0119) and venous invasion (P = 0.006), and highly favorable 5-year survival (90.9% vs 39.3% in triple-negative patients; P = 0.0032). MHC-I loss was frequent in KRAS-mutated, CD8+ CRC (P = 0.0228). No relationship was observed with CIMP, MMR, or BRAF mutation. In conclusion, tumor buds may evade immune recognition through downregulation of membranous MHC-I. A combined profile of MHC-I/CD8/TIA1 improves the prognostic value of antitumoral effector cells and should be preferred to a single marker approach.

Observation of a new type of low-frequency waves at comet 67P/Churyumov-Gerasimenko

We report on magnetic field measurements made in the innermost coma of 67P/Churyumov-Gerasimenko in its low-activity state. Quasi-coherent, large-amplitude (δ B/B ~ 1), compressional magnetic field oscillations at ~ 40 mHz dominate the immediate plasma environment of the nucleus. This differs from previously studied cometary interaction regions where waves at the cometary ion gyro-frequencies are the main feature. Thus classical pickup-ion-driven instabilities are unable to explain the observations. We propose a cross-field current instability associated with newborn cometary ion currents as a possible source mechanism.

Dual Active Bridge based Battery Charger for Plug-in Hybrid Electric Vehicle with Charging Current Containing Low Frequency Ripple

High power density is strongly preferable for the on-board battery charger of Plug-in Hybrid Electric Vehicle (PHEV). Wide band gap devices, such as Gallium Nitride HEMTs are being explored to push to higher switching frequency and reduce passive component size. In this case, the bulk DC link capacitor of AC-DC Power Factor Correction (PFC) stage, which is usually necessary to store ripple power of two times the line frequency in a DC current charging system, becomes a major barrier on power density. If low frequency ripple is allowed in the battery, the DC link capacitance can be significantly reduced. This paper focuses on the operation of a battery charging system, which is comprised of one Full Bridge (FB) AC-DC stage and one Dual Active Bridge (DAB) DC-DC stage, with charging current containing low frequency ripple at two times line frequency, designated as sinusoidal charging. DAB operation under sinusoidal charging is investigated. Two types of control schemes are proposed and implemented in an experimental prototype. It is proved that closed loop current control is the better. Full system test including both FB AC-DC stage and DAB DC-DC stage verified the concept of sinusoidal charging, which may lead to potentially very high power density battery charger for PHEV.