The antimicrobial polymer PHMB enters cells and selectively condenses bacterial chromosomes

To combat infection and antimicrobial resistance, it is helpful to elucidate drug mechanism(s) of action. Here we examined how the widely used antimicrobial polyhexamethylene biguanide (PHMB) kills bacteria selectively over host cells. Contrary to the accepted model of microbial membrane disruption by PHMB, we observed cell entry into a range of bacterial species, and treated bacteria displayed cell division arrest and chromosome condensation, suggesting DNA binding as an alternative antimicrobial mechanism. A DNA-level mechanism was confirmed by observations that PHMB formed nanoparticles when mixed with isolated bacterial chromosomal DNA and its effects on growth were suppressed by pairwise combination with the DNA binding ligand Hoechst 33258. PHMB also entered mammalian cells, but was trapped within endosomes and excluded from nuclei. Therefore, PHMB displays differential access to bacterial and mammalian cellular DNA and selectively binds and condenses bacterial chromosomes. Because acquired resistance to PHMB has not been reported, selective chromosome condensation provides an unanticipated paradigm for antimicrobial action that may not succumb to resistance

Higher non-processed red meat consumption is associated with a reduced risk of central nervous system demyelination

The evidence associating red meat consumption and risk of multiple sclerosis is inconclusive. We tested associations between red meat consumption and risk of a first clinical diagnosis of central nervous system demyelination (FCD), often presaging a diagnosis of multiple sclerosis. We used food frequency questionnaire data from the 2003-2006 Ausimmune Study, an incident, matched, case-control study examining environmental risk factors for FCD. We calculated non-processed and processed red meat density (g/1,000 kcal/day). Conditional logistic regression models (with participants matched on age, sex, and study region) were used to estimate odds ratios (ORs), 95% confidence intervals (95% CI) and p-values for associations between non-processed (n = 689, 250 cases, 439 controls) and processed (n = 683, 248 cases, 435 controls) red meat density and risk of FCD. Models were adjusted for history of infectious mononucleosis, serum 25-hydroxyvitamin D concentrations, smoking, race, education, body mass index and dietary misreporting. A one standard deviation increase in non-processed red meat density (22 g/1,000 kcal/day) was associated with a 19% reduced risk of FCD (AOR = 0.81; 95%CI 0.68, 0.97; p = 0.02). When stratified by sex, higher non-processed red meat density (per 22 g/1,000 kcal/day) was associated with a 26% reduced risk of FCD in females (n = 519; AOR = 0.74; 95%CI 0.60, 0.92; p = 0.01). There was no statistically significant association between non-processed red meat density and risk of FCD in males (n = 170). We found no statistically significant association between processed red meat density and risk of FCD. Further investigation is warranted to understand the important components of a diet that includes non-processed red meat for lower FCD risk

Smoking status and common carotid artery intima-medial thickness among middle-aged men and women based on ultrasound measurement: a cohort study

BACKGROUND: Cigarette smoking is an established causal factor for atherosclerosis. However, the smoking effect on different echogenic components of carotid arterial wall measured by ultrasound is not well elucidated. METHODS: Middle-aged men and women who had IMT measurement ≥ 0.7 mm at baseline and follow-up were included (N = 413, age 40–60 years at baseline in 1995). Intima-media thickness of common carotid artery (CCA-IMT) and its components (echogenic and echolucent layers) were measured at baseline and in the follow-up examination 3 years later. IMT and its components were compared across current, former and never smokers. Individual growth models were used to examine how smoking status was related to the baseline and progression of overall IMT and IMT components. RESULTS: For both men and women, current smoking was associated with thicker echogenic layer than never smokers; former smokers exhibited thinner echogenic layer than current smokers after adjustment for cigarette pack-years. Among women, current smoking was also associated with a thinned echolucent layer that resulted in a non-significant overall association of current smoking with IMT for women. CONCLUSION: Cigarette smoking is associated with carotid artery morphological changes and the association is sex-dependent. The atherogenic effect of smoking appears to be partly reversible among former smokers. IMT measurement alone may not be adequate to detect carotid atherosclerosis associated with cigarette smoking among middle-age women

An in vitro study comparing a peripherally inserted central catheter to a conventional central venous catheter: no difference in static and dynamic pressure transmission

<p>Abstract</p> <p>Background</p> <p>Early goal directed therapy improves survival in patients with septic shock. Central venous pressure (CVP) monitoring is essential to guide adequate resuscitation. Use of peripherally inserted central catheters (PICC) is increasing, but little data exists comparing a PICC to a conventional CVP catheter. We studied the accuracy of a novel PICC to transmit static and dynamic pressures <it>in vitro</it>.</p> <p>Methods</p> <p>We designed a device to generate controlled pressures via a column of water allowing simultaneous measurements from a PICC and a standard triple lumen catheter. Digital transducers were used to obtain all pressure readings. Measurements of static pressures over a physiologic range were recorded using 5Fr and 6Fr dual lumen PICCs. Additionally, random repetitive pressure pulses were applied to the column of water to simulate physiologic intravascular pressure variations. The resultant PICC and control waveforms were recorded simultaneously.</p> <p>Results</p> <p>Six-hundred thirty measurements were made using the 5 Fr and 6 Fr PICCs. The average bias determined by Bland-Altman plot was 0.043 mmHg for 5 Fr PICC and 0.023 mmHg for 6 Fr PICC with a difference range of 1.0 to -1.0. The correlation coefficient for both catheters was 1.0 (p-value < 0.001). Dynamic pressure waveforms plotted simultaneously between PICC and control revealed equal peaks and troughs.</p> <p>Conclusion</p> <p><it>In vitro</it>, no static or dynamic pressure differences were found between the PICC and a conventional CVP catheter. Clinical studies are required to assess whether the novel PICC has bedside equivalence to conventional catheters when measuring central venous pressures.</p

Structure of hadron resonances with a nearby zero of the amplitude

We discuss the relation between the analytic structure of the scattering amplitude and the origin of an eigenstate represented by a pole of the amplitude.If the eigenstate is not dynamically generated by the interaction in the channel of interest, the residue of the pole vanishes in the zero coupling limit. Based on the topological nature of the phase of the scattering amplitude, we show that the pole must encounter with the Castillejo-Dalitz-Dyson (CDD) zero in this limit. It is concluded that the dynamical component of the eigenstate is small if a CDD zero exists near the eigenstate pole. We show that the line shape of the resonance is distorted from the Breit-Wigner form as an observable consequence of the nearby CDD zero. Finally, studying the positions of poles and CDD zeros of the KbarN-piSigma amplitude, we discuss the origin of the eigenstates in the Lambda(1405) region.Comment: 7 pages, 3 figures, v2: published versio

Time-dependent response of a zonally averaged ocean–atmosphere–sea ice model to Milankovitch forcing

Author Posting. © The Author(s), 2010. This is the author's version of the work. It is posted here by permission of Springer-Verlag for personal use, not for redistribution. The definitive version was published in Climate Dynamics 6 (2010): 763-779, doi:10.1007/s00382-010-0790-6.An ocean-atmosphere-sea ice model is developed to explore the time-dependent response of climate to Milankovitch forcing for the time interval 5-3 Myr BP. The ocean component is a zonally averaged model of the circulation in five basins (Arctic, Atlantic, Indian, Pacific, and Southern Oceans). The atmospheric component is a one-dimensional (latitudinal) energy balance model, and the sea-ice component is a thermodynamic model. Two numerical experiments are conducted. The first experiment does not include sea ice and the Arctic Ocean; the second experiment does. Results from the two experiments are used to investigate (i) the response of annual mean surface air and ocean temperatures to Milankovitch forcing, and (ii) the role of sea ice in this response. In both experiments, the response of air temperature is dominated by obliquity cycles at most latitudes. On the other hand, the response of ocean temperature varies with latitude and depth. Deep water formed between 45°N-65°N in the Atlantic Ocean mainly responds to precession. In contrast, deep water formed south of 60°S responds to obliquity when sea ice is not included. Sea ice acts as a time-integrator of summer insolation changes such that annual mean sea-ice conditions mainly respond to obliquity. Thus, in the presence of sea ice, air temperature changes over the sea ice are amplified, and temperature changes in deep water of southern origin are suppressed since water below sea ice is kept near the freezing point.This work was supported by an NSERC Discovery Grant awarded to L.A.M. We also thank GEC3 for a Network Grant

Weight loss maintenance in women two to eleven years after participating in a commercial program: a survey

BACKGROUND: After 5 years, most reports show that less than 10% of people maintain a 5% loss from initial body weight. Weight maintenance after 10 years is rarely assessed, especially in commercial programs. The current article reports weight maintenance in individuals who had participated 2 to 11 years earlier in a popular commercial weight loss program based on Canada's Food Guide called Mincavi. METHODS: Randomly picked subjects answered a telephone questionnaire. Participants, 291 adult women from various regions of the province of Quebec, had followed the program 2 to 11 years earlier for at least a month. Body weight at the beginning and at the end of treatment was recorded as well as actual weight, age and height. Existing records allowed partial verification of the sample. RESULTS: Based on corrected weights, percentage of women who maintained at least 5% of their initial weight loss are as following; 2 years = 43.6% (n = 55), 3 years = 33.3% (n = 42), 4 years = 23.8% (n = 42), 5–6 years = 38.2% (n = 55), 7–8 years = 29.4% (n = 51), and 9–11 years; 19.6% (n = 46). Five to eleven years after they had participated in the program 29.1% of all women maintained a weight loss of at least 5%, while 14.3% maintained a loss of at least 10%. CONCLUSIONS: Even though success rate is not as high as could be wished for, results show that participation in the Mincavi program can lead to effective weight maintenance long after individuals have left it. These findings suggest more thorough studies should be conducted on this weight loss program

Reduced Population Control of an Insect Pest in Managed Willow Monocultures

BACKGROUND: There is a general belief that insect outbreak risk is higher in plant monocultures than in natural and more diverse habitats, although empirical studies investigating this relationship are lacking. In this study, using density data collected over seven years at 40 study sites, we compare the temporal population variability of the leaf beetle Phratora vulgatissima between willow plantations and natural willow habitats. METHODOLOGY/PRINCIPAL FINDINGS: The study was conducted in 1999-2005. The density of adult P. vulgatissima was estimated in the spring every year by a knock-down sampling technique. We used two measures of population variability, CV and PV, to compare temporal variations in leaf beetle density between plantation and natural habitat. Relationships between density and variability were also analyzed to discern potential underlying processes behind stability in the two systems. The results showed that the leaf beetle P. vulgatissima had a greater temporal population variability and outbreak risk in willow plantations than in natural willow habitats. We hypothesize that the greater population stability observed in the natural habitat was due to two separate processes operating at different levels of beetle density. First, stable low population equilibrium can be achieved by the relatively high density of generalist predators observed in natural stands. Second, stable equilibrium can also be imposed at higher beetle density due to competition, which occurs through depletion of resources (plant foliage) in the natural habitat. In willow plantations, competition is reduced mainly because plants grow close enough for beetle larvae to move to another plant when foliage is consumed. CONCLUSION/SIGNIFICANCE: To our knowledge, this is the first empirical study confirming that insect pest outbreak risk is higher in monocultures. The study suggests that comparative studies of insect population dynamics in different habitats may improve our ability to predict insect pest outbreaks and could facilitate the development of sustainable pest control in managed systems

Impact of lipid measurements in youth in addition to conventional clinic-based risk factors on predicting preclinical atherosclerosis in adulthood: The International Childhood Cardiovascular Cohort (i3C) Consortium

Background: Data suggest that the prediction of adult cardiovascular disease using a model comprised entirely of adult non-laboratory based risk factors is equivalent to an approach that additionally incorporates adult lipid measures. We assessed and compared the utility of a risk model based solely on non-laboratory risk factors in adolescence vs. a lipid model based on non-laboratory risk factors + lipids for predicting high-risk carotid intima-media thickness (cIMT) in adulthood. Methods: The study comprised 2,893 participants aged 12-18 years from four longitudinal cohort studies from the United States (Bogalusa Heart Study and the Insulin Study), Australia (Childhood Determinants of Adult Health Study) and Finland (The Cardiovascular Risk in Young Finns Study) and followed into adulthood when cIMT was measured (mean follow-up 23.4 years). Overweight status was defined according to the Cole classification. Hypertension was defined according to the Fourth Report on High Blood Pressure in Children and Adolescents from the National High Blood Pressure Education Program. High-risk plasma lipid levels were defined according to the National Cholesterol Education Program (NCEP) Expert Panel on Cholesterol Levels in Children. High cIMT was defined as a study-specific value ≥90th percentile. Age-and sex were included in each model. Results: In univariate models all risk factors except for borderline high-and high triglycerides in adolescence were associated with high cIMT in adulthood. In multivariable models (RR [95% CI]), male sex (2.7 [2.0-2.6]), pre-hypertension (1.4 [1.0-1.9]), hypertension (1.9 [1.3-2.9]), overweight (2.0 [1.4-2.9]), obesity (3.7 [2.0-7.0]), borderline high LDL-cholesterol (1.6 [1.2-2.2]), high LDL-cholesterol (1.6 [1.1-2.1]) and borderline low HDL-cholesterol (1.4 [1.0-1.8]) remained significant predictors of high cIMT (P always Conclusions: Non-laboratory-based risk factors and lipids measured in adolescence independently predicted preclinical atherosclerosis in young adulthood. The addition of lipid measurements to traditional clinic based risk factor assessment provided a statistically significant but clinically modest improvement on adolescent prediction of high cIMT in adulthood

Cholesterol Metabolism Is Required for Intracellular Hedgehog Signal Transduction In Vivo

We describe the rudolph mouse, a mutant with striking defects in both central nervous system and skeletal development. Rudolph is an allele of the cholesterol biosynthetic enzyme, hydroxysteroid (17-beta) dehydrogenase 7, which is an intriguing finding given the recent implication of oxysterols in mediating intracellular Hedgehog (Hh) signaling. We see an abnormal sterol profile and decreased Hh target gene induction in the rudolph mutant, both in vivo and in vitro. Reduced Hh signaling has been proposed to contribute to the phenotypes of congenital diseases of cholesterol metabolism. Recent in vitro and pharmacological data also indicate a requirement for intracellular cholesterol synthesis for proper regulation of Hh activity via Smoothened. The data presented here are the first in vivo genetic evidence supporting both of these hypotheses, revealing a role for embryonic cholesterol metabolism in both CNS development and normal Hh signaling