Fractal ventilation enhances respiratory sinus arrhythmia

BACKGROUND: Programming a mechanical ventilator with a biologically variable or fractal breathing pattern (an example of 1/f noise) improves gas exchange and respiratory mechanics. Here we show that fractal ventilation increases respiratory sinus arrhythmia (RSA) – a mechanism known to improve ventilation/perfusion matching. METHODS: Pigs were anaesthetised with propofol/ketamine, paralysed with doxacurium, and ventilated in either control mode (CV) or in fractal mode (FV) at baseline and then following infusion of oleic acid to result in lung injury. RESULTS: Mean RSA and mean positive RSA were nearly double with FV, both at baseline and following oleic acid. At baseline, mean RSA = 18.6 msec with CV and 36.8 msec with FV (n = 10; p = 0.043); post oleic acid, mean RSA = 11.1 msec with CV and 21.8 msec with FV (n = 9, p = 0.028); at baseline, mean positive RSA = 20.8 msec with CV and 38.1 msec with FV (p = 0.047); post oleic acid, mean positive RSA = 13.2 msec with CV and 24.4 msec with FV (p = 0.026). Heart rate variability was also greater with FV. At baseline the coefficient of variation for heart rate was 2.2% during CV and 4.0% during FV. Following oleic acid the variation was 2.1 vs. 5.6% respectively. CONCLUSION: These findings suggest FV enhances physiological entrainment between respiratory, brain stem and cardiac nonlinear oscillators, further supporting the concept that RSA itself reflects cardiorespiratory interaction. In addition, these results provide another mechanism whereby FV may be superior to conventional CV

Improved detection of fluorescently labeled microspheres and vessel architecture with an imaging cryomicrotome

Due to spectral overlap, the number of fluorescent labels for imaging cryomicrotome detection was limited to 4. The aim of this study was to increase the separation of fluorescent labels. In the new imaging cryomicrotome, the sample is cut in slices of 40 μm. Six images are taken for each cutting plane. Correction for spectral overlap is based on linear combinations of fluorescent images. Locations of microspheres are determined by using the system point spread function. Five differently colored microspheres were injected in vivo distributed over two major coronaries, the left anterior descending and left circumflex artery. Under absence of collateral flow, microspheres outside of target perfusion territories were not found and the procedure did not generate false positive detection when spectral overlap was relevant. In silico-generated microspheres were used to test the effect of background image, transparency correction, and color separation. The percentage of microspheres undetected was 2.3 ± 0.8% in the presence and 1.5 ± 0.4% in the absence of background structures with a density of 900 microspheres per color per cm3. The image analysis method presented here, allows for an increased number of experimental conditions that can be investigated in studies of regional myocardial perfusion

Branch Mode Selection during Early Lung Development

Many organs of higher organisms, such as the vascular system, lung, kidney, pancreas, liver and glands, are heavily branched structures. The branching process during lung development has been studied in great detail and is remarkably stereotyped. The branched tree is generated by the sequential, non-random use of three geometrically simple modes of branching (domain branching, planar and orthogonal bifurcation). While many regulatory components and local interactions have been defined an integrated understanding of the regulatory network that controls the branching process is lacking. We have developed a deterministic, spatio-temporal differential-equation based model of the core signaling network that governs lung branching morphogenesis. The model focuses on the two key signaling factors that have been identified in experiments, fibroblast growth factor (FGF10) and sonic hedgehog (SHH) as well as the SHH receptor patched (Ptc). We show that the reported biochemical interactions give rise to a Schnakenberg-type Turing patterning mechanisms that allows us to reproduce experimental observations in wildtype and mutant mice. The kinetic parameters as well as the domain shape are based on experimental data where available. The developed model is robust to small absolute and large relative changes in the parameter values. At the same time there is a strong regulatory potential in that the switching between branching modes can be achieved by targeted changes in the parameter values. We note that the sequence of different branching events may also be the result of different growth speeds: fast growth triggers lateral branching while slow growth favours bifurcations in our model. We conclude that the FGF10-SHH-Ptc1 module is sufficient to generate pattern that correspond to the observed branching modesComment: Initially published at PLoS Comput Bio

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

Radiomics-based differentiation of lung disease models generated by polluted air based on X-ray computed tomography data

BACKGROUND: Lung diseases (resulting from air pollution) require a widely accessible method for risk estimation and early diagnosis to ensure proper and responsive treatment. Radiomics-based fractal dimension analysis of X-ray computed tomography attenuation patterns in chest voxels of mice exposed to different air polluting agents was performed to model early stages of disease and establish differential diagnosis. METHODS: To model different types of air pollution, BALBc/ByJ mouse groups were exposed to cigarette smoke combined with ozone, sulphur dioxide gas and a control group was established. Two weeks after exposure, the frequency distributions of image voxel attenuation data were evaluated. Specific cut-off ranges were defined to group voxels by attenuation. Cut-off ranges were binarized and their spatial pattern was associated with calculated fractal dimension, then abstracted by the fractal dimension -- cut-off range mathematical function. Nonparametric Kruskal-Wallis (KW) and Mann-Whitney post hoc (MWph) tests were used. RESULTS: Each cut-off range versus fractal dimension function plot was found to contain two distinctive Gaussian curves. The ratios of the Gaussian curve parameters are considerably significant and are statistically distinguishable within the three exposure groups. CONCLUSIONS: A new radiomics evaluation method was established based on analysis of the fractal dimension of chest X-ray computed tomography data segments. The specific attenuation patterns calculated utilizing our method may diagnose and monitor certain lung diseases, such as chronic obstructive pulmonary disease (COPD), asthma, tuberculosis or lung carcinomas

Systematic Review of Potential Health Risks Posed by Pharmaceutical, Occupational and Consumer Exposures to Metallic and Nanoscale Aluminum, Aluminum Oxides, Aluminum Hydroxide and Its Soluble Salts

Aluminum (Al) is a ubiquitous substance encountered both naturally (as the third most abundant element) and intentionally (used in water, foods, pharmaceuticals, and vaccines); it is also present in ambient and occupational airborne particulates. Existing data underscore the importance of Al physical and chemical forms in relation to its uptake, accumulation, and systemic bioavailability. The present review represents a systematic examination of the peer-reviewed literature on the adverse health effects of Al materials published since a previous critical evaluation compiled by Krewski et al. (2007). Challenges encountered in carrying out the present review reflected the experimental use of different physical and chemical Al forms, different routes of administration, and different target organs in relation to the magnitude, frequency, and duration of exposure. Wide variations in diet can result in Al intakes that are often higher than the World Health Organization provisional tolerable weekly intake (PTWI), which is based on studies with Al citrate. Comparing daily dietary Al exposures on the basis of “total Al”assumes that gastrointestinal bioavailability for all dietary Al forms is equivalent to that for Al citrate, an approach that requires validation. Current occupational exposure limits (OELs) for identical Al substances vary as much as 15-fold. The toxicity of different Al forms depends in large measure on their physical behavior and relative solubility in water. The toxicity of soluble Al forms depends upon the delivered dose of Al+ 3 to target tissues. Trivalent Al reacts with water to produce bidentate superoxide coordination spheres [Al(O2)(H2O4)+ 2 and Al(H2O)6 + 3] that after complexation with O2•−, generate Al superoxides [Al(O2•)](H2O5)]+ 2. Semireduced AlO2• radicals deplete mitochondrial Fe and promote generation of H2O2, O2 • − and OH•. Thus, it is the Al+ 3-induced formation of oxygen radicals that accounts for the oxidative damage that leads to intrinsic apoptosis. In contrast, the toxicity of the insoluble Al oxides depends primarily on their behavior as particulates. Aluminum has been held responsible for human morbidity and mortality, but there is no consistent and convincing evidence to associate the Al found in food and drinking water at the doses and chemical forms presently consumed by people living in North America and Western Europe with increased risk for Alzheimer\u27s disease (AD). Neither is there clear evidence to show use of Al-containing underarm antiperspirants or cosmetics increases the risk of AD or breast cancer. Metallic Al, its oxides, and common Al salts have not been shown to be either genotoxic or carcinogenic. Aluminum exposures during neonatal and pediatric parenteral nutrition (PN) can impair bone mineralization and delay neurological development. Adverse effects to vaccines with Al adjuvants have occurred; however, recent controlled trials found that the immunologic response to certain vaccines with Al adjuvants was no greater, and in some cases less than, that after identical vaccination without Al adjuvants. The scientific literature on the adverse health effects of Al is extensive. Health risk assessments for Al must take into account individual co-factors (e.g., age, renal function, diet, gastric pH). Conclusions from the current review point to the need for refinement of the PTWI, reduction of Al contamination in PN solutions, justification for routine addition of Al to vaccines, and harmonization of OELs for Al substances