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Background Using an optical method based on tunable diode laser absorption spectroscopy, we previously assessed oxygen (O2) and water vapor (H2O) content in a tissue phantom of the preterm infant lung. Here we applied this method on newborn piglets with induced lung complications. Methods Five mechanically ventilated piglets were subjected to stepwise increased and decreased fraction of inspired oxygen (FiO2), to atelectasis using a balloon catheter in the right bronchus, and to pneumothorax by injecting air in the pleural cavity. Two diode lasers (764 nm for O2 gas absorption and 820 nm for H2O absorption) were combined in a probe delivering light either externally, on the skin, or internally, through the esophagus. The detector probe was placed dermally. Results Calculated O2 concentrations increased from 20% (IQR 17−23%) when ventilated with room air to 97% (88−108%) at FiO2 1.0. H2O was only detectable with the internal light source. Specific light absorption and transmission patterns were identified in response to atelectasis and pneumothorax, respectively. Conclusions The optical method detected FiO2 variations and discriminated the two induced lung pathologies, providing a rationale for further development into a minimally invasive device for real-time monitoring gas changes in the lungs of sick newborn infants. Impact Optical spectroscopy can detect pulmonary complications in an animal model.Oxygen concentrations can be evaluated in the lungs.Presents a novel minimally invasive method to detect lung oxygenation and complications.Potential to be developed into a lung monitoring method in newborn infants.Potential for bed-side detection of pulmonary complications in newborn infants.

Background Vasomotion is the spontaneous oscillation in vascular tone in the microcirculation and is believed to be a physiological mechanism facilitating the transport of blood gases and nutrients to and from tissues. So far, Laser Doppler flowmetry has constituted the gold standard for in vivo vasomotion analysis. Materials and methods We applied vasomotion analysis to speed-resolved perfusion, oxygen saturation, red blood cell tissue (RBC) tissue fraction, and average vessel diameter from five healthy individuals at rest measured by the newly developed Periflux 6000 EPOS system over 10 minutes. Magnitude scalogram and the time-averaged wavelet spectra were divided into frequency intervals reflecting endothelial, neurogenic, myogenic, respiratory, and cardiac function. Results Recurrent high-intensity periods of the myogenic, neurogenic, and endothelial frequency intervals were found. The neurogenic activity was considerably more pronounced for the oxygen saturation, RBC tissue fraction, and vessel diameter signals, than for the perfusion signals. In a correlation analysis we found that changes in perfusion in the myogenic, neurogenic, and endothelial frequency intervals precede changes in the other signals. Furthermore, changes in average vessel diameter were in general negatively correlated to the other signals in the same frequency intervals, indicating the importance of capillary recruitment. Conclusion We conclude that vasomotion can be observed in signals reflecting speed resolved perfusion, oxygen saturation, RBC tissue fraction, and vessel diameter. The new parameters enable new aspects of the microcirculation to be observed.

Significance: Hemoglobin oxygen saturation and red blood cell (RBC) tissue fraction are important parameters when assessing microvascular status. Functional information can be attained using temporally resolved measurements performed during stimulus–response protocols. Pointwise assessments can currently be conducted with probe-based systems. However, snapshot multispectral imaging (MSI) can be used for spatial–temporal measurements. Aim: To validate if hemoglobin oxygen saturation and RBC tissue fraction can be quantified using a snapshot MSI system and an inverse Monte Carlo algorithm. Approach: Skin tissue measurements from the MSI system were compared to those from a validated probe-based system during arterial and venous occlusion provocation on 24 subjects in the wavelength interval 450 to 650 nm, to evaluate a wide range of hemoglobin oxygen saturation and RBC tissue fraction levels. Results: Arterial occlusion results show a mean linear regression R2 = 0.958 for hemoglobin oxygen saturation. Comparing relative RBC tissue fraction during venous occlusion results in R2 = 0.925. The MSI system shows larger dynamic changes than the reference system, which might be explained by a deeper sampling including more capacitance vessels. Conclusions: The snapshot MSI system estimates hemoglobin oxygen saturation and RBC tissue fraction in skin microcirculation showing a high correlation (R2 > 0.9 in most subjects) with those measured by the reference method. Funding: Swedens Innovation Agency VINNOVA via the programs Swelife and MedTech4Health [2017-01435, 2019-01522]; CENIIT research organization within Linkoping University [11.02]

The objective of this study was to explore the associations between skin microcirculatory function and established cardiovascular risk factors in a large Swedish cohort. As part of the Swedish CArdioPulmonary bioImage Study (SCAPIS), microcirculatory data were acquired at Linkoping University hospital, Linkoping, Sweden during 2016–2017. The subjects, aged 50–64 years, were randomly selected from the national population register. Microcirculatory reactivity was assessed using a 5-min arterial occlusion-release protocol. Comprehensive skin microcirculatory data were continuously acquired by using a fiberoptic probe placed on the lower right arm. After exclusion of missing data (208), 1557 subjects were remaining. Among the parameters, skin microcirculatory peak oxygen saturation after occlusion release, had the strongest relationship to the cardiovascular risk factors. The linear associations between peak oxygen saturation and cardiovascular risk factors were analyzed adjusted for age and sex. We found a negative association with peak oxygen saturation (standardized regression coefficient) for blood pressure (systolic −0.05 (95% CI: −0.10;-0.003) and diastolic −0.05 (−0.10; −0.003)), BMI −0.18 (−0.23; −0.13), waist circumference (males −0.20 (−0.32; −0.16), females −0.18 (−0.25; −0.11)), prevalent diabetes −0.31 (−0.49; −0.12), hypertension −0.30 (−0.42; −0.18), hyperlipidemia −0.24 (−0.40; −0.09), fasting glucose level −0.06 (−0.12; −0.01), HbA1c −0.07 (−0.12; −0.02), triglyceride level −0.09 (−0.14; −0.04), hsCRP −0.12 (−0.17; −0.07), and current smoker versus never smoked −0.50 (−0.67; −0.34). A positive association with peak oxygen saturation was found for cholesterol level 0.05 (0.005; 0.11) and HDL 0.11 (0.06; 0.17). This is the first study showing that post-ischemic skin microvascular peak oxygen saturation is associated with virtually all established cardiovascular risk factors in a population-based middle-aged cohort.

Several studies have shown that advanced glycation end products (AGE) play a role in both the microvascular and macrovascular complications of diabetes and are closely linked to inflammation and atherosclerosis. AGEs accumulate in skin and can be detected using their auto fluorescence (AF).A significant correlation exists between AGE AF and the levels of AGEs as obtained from skin biopsies. A commercial device, the AGE Reader, has become available to assess skin AF for clinical purposes but, while displaying promising results, it is limited to single-point measurements performed in contact to skin tissue. Furthermore, in vivo imaging of AGE accumulation is virtually unexplored.We proposed a non-invasive, contact-less novel technique for quantifying fluorescent AGE deposits in skin tissue using a multispectral imaging camera setup (MSI) during ultraviolet (UV) exposure. Imaging involved applying a region-of-interest mask, avoiding specular reflections and a simple calibration. Results of a study conducted on 16 subjects with skin types ranging from fair to deeply pigmented skin, showed that AGE measured with MSI in forearm skin was significantly correlated with the AGE reference method (AGE Reader on forearm skin, R=0.68, p=0.005). AGE measured in facial skin was borderline significantly related to AGE Reader on forearm skin (R=0.47, p=0.078). These results support the use of the technique in devices for non-touch measurement of AGE content in either facial or forearm skin tissue over time. SEMEOTICONS

The aim of this study was to determine the optical absorption and scattering properties in a large Swedish cohort including 1765 subjects. The study was performed in the Linkoping site within the national multicenter Swedish CArdioPulmonary bioImage Study (SCAPIS), a world unique study including detailed imaging and functional analysis of heart, vessels and lungs in 30 000 men and women in Sweden to predict and prevent cardiovascular disease and chronic obstructive pulmonary disease. The subjects, men and women between 50 and 64 years old, were randomly selected and recruited from the population registry in Sweden. Measurements on the volar forearm were performed at baseline and during a systolic occlusion provocation with an integrated system, including spatially resolved diffuse reflectance spectroscopy and laser Doppler flowmetry. Data were analyzed with an inverse Monte Carlo algorithm, accounting for both scattering, geometrical and absorbing properties of the tissue. The absorption coefficient was assumed to differ between the epidermis and the two dermis layers, while the reduced scattering coefficient was equal in all layers. The reduced scattering coefficient (@ 650 nm) was (M ± SD) = 1.68 ± 0.34 mm-1. Gender was found to significant change the fraction of small scattering particles and the reduced scattering coefficient. The absorption coefficient (@ 650 nm) for the dermis layers was 0.010 ± 0.005 mm-1. This large study on optical properties of skin can serve as reference values and provide new knowledge on how factors like gender, age, BMI etc. affect the optical properties.

Newborn infants may have pulmonary disorders with abnormal gas distribution, e.g., respiratory distress syndrome. Pulmonary radiography is the clinical routine for diagnosis. Our aim was to investigate a novel noninvasive optical technique for rapid nonradiographic bedside detection of oxygen gas in the lungs of full-term newborn infants.Laser spectroscopy was used to measure contents of oxygen gas (at 760 nm) and of water vapor (at 937 nm) in the lungs of 29 healthy newborn full-term infants (birth weight 2,900-3,900 g). The skin above the lungs was illuminated using two low-power diode lasers and diffusely emerging light was detected with a photodiode.Of the total 390 lung measurements performed, clear detection of oxygen gas was recorded in 60%, defined by a signal-to-noise ratio of3. In all the 29 infants, oxygen was detected. Probe and detector positions for optimal pulmonary gas detection were determined. There were no differences in signal quality with respect to gender, body side or body weight.The ability to measure pulmonary oxygen content in healthy full-term neonates with this technique suggests that with further development, the method might be implemented in clinical practice for lung monitoring in neonatal intensive care.

Spatial frequency domain imaging (SFDI) utilizes a digital light processing (DLP) projector for illuminating turbid media with sinusoidal patterns. The tissue absorption (μ a ) and reduced scattering coefficient (μ , s ) are calculated by analyzing the modulation transfer function for at least two spatial frequencies. We evaluated different illumination strategies with a red, green and blue light emitting diodes (LED) in the DLP, while imaging with a filter mosaic camera, XiSpec, with 16 different multi-wavelength sensitive pixels in the 470-630 nm wavelength range. Data were compared to SFDI by a multispectral camera setup (MSI) consisting of four cameras with bandpass filters centered at 475, 560, 580 and 650 nm. A pointwise system for comprehensive microcirculation analysis was used (EPOS) for comparison. A 5-min arterial occlusion and release protocol on the forearm of a Caucasian male with fair skin was analyzed by fitting the absorption spectra of the chromophores HbO 2 , Hb and melanin to the estimatedμ a . The tissue fractions of red blood cells ( f RBC), melanin (/mel) and the Hb oxygenation ( S 0 2 ) were calculated at baseline, end of occlusion, early after release and late after release. EPOS results showed a decrease in S 0 2 during the occlusion and hyperemia during release ( S 0 2 = 40%, 5%, 80% and 51%). The f RBC showed an increase during occlusion and release phases. The best MSI resemblance to the EPOS was for green LED illumination ( S 0 2 = 53%, 9%, 82%, 65%). Several illumination and analysis strategies using the XiSpec gave un-physiological results (e.g. negative S 0 2 ). XiSpec with green LED illumination gave the expected change in /RBC , while the dynamics in S 0 2 were less than those for EPOS. These results may be explained by the calculation of modulation using an illumination and detector setup with a broad spectral transmission bandwidth, with considerable variation in μ a of included chromophores. Approaches for either reducing the effective bandwidth of the XiSpec filters or by including their characteristic in a light transport model for SFDI modulation, are proposed.

The lipid–protein mixture that covers the lung alveoli, lung surfactant, ensures mechanical robustness and controls gas transport during breathing. Lung surfactant is located at an interface between water-rich tissue and humid, but not fully saturated, air. The resulting humidity difference places the lung surfactant film out of thermodynamic equilibrium, which triggers the buildup of a water gradient. Here, we present a millifluidic method to assemble multilamellar interfacial films from vesicular dispersions of a clinical lung surfactant extract used in replacement therapy. Using small-angle X-ray scattering, infrared, Raman, and optical microscopies, we show that the interfacial film consists of several coexisting lamellar phases displaying a substantial variation in water swelling. This complex phase behavior contrasts to observations made under equilibrium conditions. We demonstrate that this disparity stems from additional lipid and protein gradients originating from differences in their transport properties. Supplementing the extract with cholesterol, to levels similar to the endogenous lung surfactant, dispels this complexity. We observed a homogeneous multilayer structure consisting of a single lamellar phase exhibiting negligible variations in swelling in the water gradient. Our results demonstrate the necessity of considering nonequilibrium thermodynamic conditions to study the structure of lung surfactant multilayer films, which is not accessible in bulk or monolayer studies. Our reconstitution methodology also opens avenues for lung surfactant pharmaceuticals and the understanding of composition, structure, and property relationships at biological air–liquid interfaces., Composition gradients develop across lung surfactant films under physiologically relevant nonequilibrium conditions, yielding a structural heterogeneity that is suppressed by cholesterol addition.

Skin and kidney microvascular functions may be affected independently in diabetes mellitus. We investigated skin microcirculatory function in 79 subjects with diabetes type 2, where 41 had microalbuminuria and 38 not, and in 41 age-matched controls. The oxygen saturation, fraction of red blood cells and speed-resolved microcirculatory perfusion (% red blood cells × mm/s) divided into three speed regions: 0–1, 1–10 and above 10 mm/s, were assessed during baseline and after local heating of the foot with a new device integrating diffuse reflectance spectroscopy and laser Doppler flowmetry. Arterial stiffness was assessed as carotid-femoral pulse wave velocity. Subjects with diabetes and microalbuminuria had significantly higher carotid-femoral pulse wave velocity compared to subjects without microalbuminuria and to controls. The perfusion for speeds 0–1 mm/s and red blood cell tissue fraction were reduced in subjects with diabetes at baseline and after heating, independent of microalbuminuria. These parameters were correlated to HbA1c. In conclusion, the reduced nutritive perfusion and red blood cell tissue fraction in type 2 diabetes were related to long-term glucose control but independent of microvascular changes in the kidneys and large-vessel stiffness. This may be due to different pathogenic pathways in the development of nephropathy, large-vessel stiffness and cutaneous microvascular impairment.

The lipid–protein film covering the interface of the lung alveolar in mammals is vital for proper lung function and its deficiency is related to a range of diseases. Here we present a molecular-level characterization of a clinical-grade porcine lung surfactant extract using a multitechnique approach consisting of H 1 – C 13 solid-state nuclear magnetic spectroscopy, small- and wide-angle X-ray scattering, and mass spectrometry. The detailed characterization presented for reconstituted membranes of a lung extract demonstrates that the molecular structure of lung surfactant strongly depends on the concentration of cholesterol. If cholesterol makes up about 11% of the total dry weight of lung surfactant, the surfactant extract adopts a single liquid-ordered lamellar phase, L α ( o ) , at physiological temperatures. This L α ( o ) phase gradually changes into a liquid-disordered lamellar phase, L α ( d ) , when the temperature is increased by a few degrees. In the absence of cholesterol the system segregates into one lamellar gel phase and one L α ( d ) phase. Remarkably, it was possible to measure a large set of order parameter magnitudes | S CH | from the liquid-disordered and -ordered lamellar phases and assign them to specific C–H bonds of the phospholipids in the biological extract with no use of isotopic labeling. These findings with molecular details on lung surfactant mixtures together with the presented NMR methodology may guide further development of pulmonary surfactant pharmaceuticals that better mimic the physiological self-assembly compositions for treatment of pathological states such as respiratory distress syndrome.

The alveolar interface is covered by film composed of lipids and proteins, generally referred to as “lung surfactant”. It has several important functional roles, including stabilizing the interface, allowing for area expansions and controlling diffusional transport. Prematurely born babies can develop neonatal respiratory distress syndrome (NRDS) due to deficiencies of lung surfactant. This syndrome, if left untreated, is lethal. We aim to further understand the structure and formation of the interfacial film.The majority of biophysical studies of model systems for the alveolar interface focus on single monolayers. However, several studies of lung surfactant extracts have demonstrated formation of multilayer interfacial structures [1-3] suggesting that this might also be the situation in the endogenous system.In this study we use Curosurf, an extract used in clinics to treat infants suffering from NRDS. We have characterized a similar extract in the bulk phase using ssNMR and SAXS/WAXS showing co-existing lamellar phases (liquid disordered/ordered and gel phase). Furthermore we have been able to resolve order parameters for the acyl chains of the lipids in the biological extract of lung surfactant.We use neutron reflectometry to study the lung surfactant at the air-water interface under controlled high humidity and under repeated compression-expansion cycles in order to mimic the work of breathing. We demonstrate multilayer formation at the interface and how the film responds to compression-expansion cycles. Moreover, we show how the structure of the film evolves under the cycles, the effect of ion composition and how the film thickness reaches a steady state.1. Schurch et al. 1995, Biol. Neonate, 67, 61-76.2. Perez-Gil et al. 2008, Biochim. Biophys. Acta-Biomembr. 1778, 1676-1695.3. Follows et al. 2007, Biochim. Biophys. Acta 1768, 228-235.

The main purpose of this study was to investigate a novel non-invasive optical technique for rapid bedside detection of oxygen gas in the lungs of full-term newborn infants. The results suggest that the technique will be clinically useful.

Aim: To expand the treatment options in paediatric Gorham-Stout syndrome (GSS) when conventional therapy is ineffective. Method: Two children with biopsy confirmed GSS, a rare disorder with progressive lymphangiomatosis, were treated with a combination of interferon-alpha-2b, low anticoagulant, low molecular weight heparin, radiotherapy and surgery. Results: The combined therapy resolved the symptoms in the acute phase, and both patients have since been free of symptoms for >2 years. Conclusion: The successful addition of a low anticoagulant, low molecular weight heparin ( tafoxiparin) to the treatment protocol in two paediatric cases of the GSS may justify the use of this approach in similar cases.

Endothelial function is important for regulating peripheral blood flow to meet varying metabolic demands and can be measured indirectly during vascular provocations. In this study, we compared the PAT finger response (EndoPAT) after a 5-minutes arterial occlusion to that from forearm skin comprehensive microcirculation analysis (EPOS).Measurements in 16 subjects with varying cardiovascular risk factors were carried out concurrently with both methods during arterial occlusion, while forearm skin was also evaluated during local heating.Peak values for EPOS skin PerfWe have demonstrated for the first time a significant relationship between forearm skin microcirculatory perfusion and oxygen saturation and finger PAT. Both local heating and reactive hyperemia are useful skin provocations. Further studies are needed to understand the precise regulation mechanisms of blood flow and oxygenation during these tests.

We have developed a new fiber-optic system that combines diffuse reflectance spectroscopy (DRS) and laser Doppler Flowmetry (LDF) for a multi-modal assessment of the microcirculation. Quantitative data is achieved with an inverse Monte Carlo algorithm based on an individually adaptive skin model. The output parameters are calculated from the model and given in absolute units: hemoglobin oxygen saturation (%), red blood cell (RBC) tissue fraction (%), and the speed resolved RBC perfusion separated into three speed regions; 0–1 mm/s, 1–10 mm/s and above 10 mm/s (% mm/s). The aim was to explore microcirculatory parameters using the new optical method, integrating DRS and LDF in a joint skin model, during local heating of the dorsal foot and venous and arterial occlusion of the forearm in 23 healthy subjects (age 20–28 years). There were differences in the three speed regions in regard to blood flow changes due to local heating, where perfusion for high speeds increased the most. There was also a high correlation between changes in oxygenation and changes in perfusion for higher speeds. Oxygen saturation at baseline was 44% on foot, increasing to 83% at plateau after heating. The larger increase in perfusion for higher speeds than for lower speeds together with the oxygenation increase during thermal provocation, shows a local thermoregulatory blood flow in presumably arteriolar dermal vessels. In conclusion, there are improved possibilities to assess microcirculation using integrated DRS and LDF in a joint skin model by enabling both oxygenation and speed resolved blood flow assessment simultaneously and in the same skin site. Output parameters in absolute units may also yield new insights about the microcirculatory system. Funding text: VINNOVA (Swedens innovation agency); Perimed AB through the SamBIO research collaboration program [2008-00149]; Research&Grow program (VINNOVA) [2011-03074]; NovaMedTech - European Union Regional Development Fund [68737, 160382]

Hypercholesterolemia is characterized by high blood levels of cholesterol and is associated with increased risk of atherosclerosis and cardiovascular disease. Xanthelasma is a subcutaneous lesion appearing in the skin around the eyes. Xanthelasma is related to hypercholesterolemia. Identifying micro-xanthelasma can thereforeprovide a mean for early detection of hypercholesterolemia and prevent onset and progress of disease. The goal of this study was to investigate spectral and spatial characteristics of hypercholesterolemia in facial skin. Optical techniques like hyperspectral imaging (HSI) might be a suitable tool for such characterization as it simultaneously provides high resolution spatial and spectral information. In this study a 3D Monte Carlo model of lipid inclusions in human skin was developed to create hyperspectral images in the spectral range 400-1090 nm. Four lesions with diameters 0.12–1.0 mm were simulated for three different skin types. The simulations were analyzed using three algorithms: the Tissue Indices (TI), the two layer Diffusion Approximation (DA), and the Minimum Noise Fraction transform (MNF). The simulated lesions were detected by all methods, but the best performance was obtained by the MNF algorithm. The results were verified using data from 11 volunteers with known cholesterol levels. The face of the volunteers was imaged by a LCTF system (400- 720 nm), and the images were analyzed using the previously mentioned algorithms. The identified features were then compared to the known cholesterol levels of the subjects. Significant correlation was obtained for the MNF algorithm only. This study demonstrates that HSI can be a promising, rapid modality for detection of hypercholesterolemia.

This study investigates the interactions between a porcine lung surfactant (PLS) extract and distilled water, saline solution or Ringer solution. The phases which coexist in equilibrium with water or electrolyte solutions were analysed by X-ray diffraction and cryo transmission electron microscopy (cryo-TEM). A lamellar phase with a structure unit consisting of double bilayers was observed in water, whereas lamellar phases with the usual bilayer structure unit were formed in saline and in Ringer solutions. At 25 degrees C the presence of a 4.2-A peak in the X-ray diffraction wide-angle region of these three maximally swollen phases showed that most of the hydrocarbon chains were organized in a crystalline packing. At 42 degrees C the chains in all three phases were melted which, in combination with the low-angle diffraction, shows that they were liquid-crystalline. Polyhedral-like vesicles and spherically shaped multilamellar vesicles were observed in cryo-TEM. The bilayer unit structures were consistent with the periodicity seen by X-ray diffraction. The dynamic swelling behaviour was followed in the polarizing microscope. A remarkable growth of birefringent networks was seen at the air interface of samples swollen in Ringer solution and saline solution. No such interfacial growth phenomena were observed during swelling in water without electrolytes. Then, these dynamics were analysed in relation to time-dependent pulmonary administration of the surfactant extract in rats. Variation in the time of administration (20 and 60 min) after mixing the extract with saline or Ringer solution showed clear differences in physiological effects. At pulmonary administration when the swelling behaviour in vitro showed a maximum in dynamics, the arterial oxygenation was superior to that of administration at a time after a steady-state had been reached. This means that the clinical performance of mammalian lung surfactant extracts can be significantly improved by taking the time-dependent aqueous swelling of the extract into account.

Adopting a multidisciplinary approach with input from physicists, researchers and medical professionals, this is the first book to introduce many different technical approaches for the visualizatio ...

Intramyocardial oxygen transport was assessed during open-chest surgery in calves by diffuse reflectance spectroscopy using a small intramuscular fiber-optic probe. The sum of hemo- and myoglobin tissue fraction and oxygen saturation, the tissue fraction and oxidation of cytochrome aa3, and the tissue fraction of methemoglobin were estimated using a calibrated empirical light transport model. Increasing the oxygen content in the inhaled gas, 21%-50%-100%, in five calves (group A) gave an increasing oxygen saturation of 19+/-4%, 24+/-5%, and 28+/-8% (p0.001, ANOVA repeated measures design) and mean tissue fractions of 1.6% (cytochrome aa3) and 1.1% (hemo- and myoglobin). Cardiac arrest in two calves gave an oxygen saturation lower than 5%. In two calves (group B), a left ventricular assistive device (LVAD pump) was implanted. Oxygen saturation in group B animals increased with LVAD pump speed (p0.001, ANOVA) and with oxygen content in inhaled gas (p0.001, ANOVA). The cytochrome aa3 oxidation level was above 96% in both group A and group B calves, including the two cases involving cardiac arrest. In conclusion, the estimated tissue fractions and oxygenation/oxidation levels of the myocardial chromophores during respiratory and hemodynamic provocations were in agreement with previously presented results, demonstrating the potential of the method.

OBJECTIVE-To compare the microcirculatory velocity distribution in type 2 diabetic patients and nondiabetic control subjects at baseline and after local heating. RESEARCH DESIGN AND METHODS-The skin blood flow response to local heating (44 degrees C for 20 mm) was assessed in 28 diabetic patients and 29 control subjects using a new velocity-resolved quantitative laser Doppler flowmetry technique (qLDF). The qLDF estimates erythrocyte (RBC) perfusion (velocity X concentration), in a physiologically relevant unit (grams RBC per 100 g tissue X millimeters per second) in a fixed output volume, separated into three velocity regions: v less than1 mm/s, v 1-10 mm/s, and v greater than10 mm/s. RESULTS-The increased blood flow occurs in vessels with a velocity greater than1 mm/s. A significantly lower response in qLDF total perfusion was found in diabetic patients than in control subjects after heat provocation because of less high-velocity blood flow (v greater than10 mm/s). The RBC concentration in diabetic patients increased sevenfold for v between 1 and 10 mm/s, and 15-fold for v greater than10 mm/s, whereas no significant increase was found for v less than1 mm/s. The mean velocity increased from 0.94 to 7.3 mm/s in diabetic patients and from 0.83 to 9.7 mm/s in control subjects. CONCLUSIONS-The perfusion increase occurs in larger shunting vessels and not as an increase in capillary flow. Baseline diabetic patient data indicated a redistribution of flow to higher velocity regions, associated with longer duration of diabetes. A lower perfusion was associated with a higher BMI and a lower toe-to-brachial systolic blood pressure ratio. This is an author-created, uncopyedited electronic version of an article accepted for publication in Diabetes. The American Diabetes Association (ADA), publisher of Diabetes, is not responsible for any errors or omissions in this version of the manuscript or any version derived from it by third parties. The definitive publisher-authenticated version is online at http://diabetes.diabetesjournals.org.:Ingemar Fredriksson, Marcus Larsson, Fredrik Nyström, Toste Länne, Carl Johan Östgren and Tomas Strömberg, Reduced Arteriovenous Shunting Capacity After Local Heating and Redistribution of Baseline Skin Blood Flow in Type 2 Diabetes Assessed With Velocity-Resolved Quantitative Laser Doppler Flowmetry, 2010, Diabetes, (59), 7, 1578-1584.http://dx.doi.org/10.2337/db10-0080Copyright: American Diabetes Association Inc / American Diabetes Association; 1999http://www.diabetes.org/

Transcranial magnetic stimulation (TMS) with weak (micro Tesla) complex waveform fields have been claimed to evoke the sensed presence of a sentient being in up to 80% in the general population. These findings have had a questionable neurophysiological foundation as the fields are approximately six orders of magnitude weaker than ordinary TMS fields. Also, no independent replication has been reported. To replicate and extend previous findings, we performed a double-blind experiment (N = 89), with a sham-field control group. Personality characteristics indicating suggestibility (absorption, signs of abnormal temporal lobe activity, and a "new age"-life-style orientation) were used as predictors. Sensed presence, mystical, and other somatosensory experiences previously reported from the magnetic field stimulation were outcome measures. We found no evidence for any effects of the magnetic fields, neither in the entire group, nor in individuals high in suggestibility. Because the personality characteristics significantly predicted outcomes, suggestibility may account for previously reported effects. Our results strongly question the earlier claims of experiential effects of weak magnetic fields. (Less)

Aim To evaluate the instrument Measure of Processes of Care (MPOC) in a Swedish context. Methods The MPOC consists of 56 questions in the five scales: enabling and partnership; providing general information; providing specific information about the child; co-ordinated and comprehensive care; and respectful and supportive care. The questionnaire was translated into Swedish and distributed to 850 families, served by four habilitation centres. After two reminders, a response rate of 74.9% was obtained, and about 60% of the questionnaires qualified for further statistical analysis. Reliability, calculated as Cronbach's alpha, was high for four of the five scales and acceptable for the fifth (scale no. 3). Results Significant differences were shown between centres as well as between age groups. These differences were reasonable as judged through background knowledge, indicating that the instrument was able to discriminate between actual differences in services. Commenting on the practical use of the questionaire, staff, as well as responding parents, found the questionnaire rather long and some parents reported difficulties in giving answers as specific as the questionnaire asked them to. Conclusion The MPOC shows sufficient sensitivity to be used as an evaluation tool for services at a centre or program level, and can be recommended for research and practical use.

Hepatocyte growth factor (HGF) is a heparin-binding protein with mitogenic, motogenic and morphogenic activities for various cell types. The regenerative properties of HGF have been the object of several animal and in vitro studies in recent years.To investigate the physiological and therapeutic effects of HGF on chronic leg ulcers.HGF in gel form was locally applied, once daily for 7 days, to 15 of 19 chronic leg ulcers in 11 elderly patients. All patients had previously been treated by conventional methods and their leg ulcers had been in stable conditions for between 1 and 14 years. Any signs of allergy, discomfort or pain were reported daily. Microcirculation perfusion in the ulcers, compared to the intact contiguous skin, was determined by laser Doppler at the beginning of the study, after 1 week and again after 3 months (in seven patients). Ulcer size and characteristics were also documented.It was observed that microcirculatory perfusion, which might reflect the angiogenic effect of HGF, was statistically significantly correlated (r = 0.94, p0.002) to ulcer area reduction in the treated ulcers. Excellent (84-100% area reduction) or partial healing (58-59%) was seen in eight out of 11 patients. No control group was included in this pilot study, which must be completed by proper control studies.This study suggests that HGF may heal chronic leg ulcers, possibly by improving the microcirculation. Proper control studies need to be performed.

The microvascular perfusion can be measured using laser Doppler blood flowmetry (LDF), a technique sensitive to the concentration of moving blood cells and their velocity. However, movements of the tissue itself can cause artifacts in the perfusion readings. In a clinical situation, these movement induced artifacts may arise from patient movements or from movements of internal organs e.g. the intestines or the beating heart. Therefore, we have studied how a well-controlled tissue movement affects the LDF signals during different flow conditions and for different surface structures. Tissue perfusion was recorded non-touch in one point using a laser Doppler perfusion imager. During the measurements the object was placed on a shaker that generated the movement (both horizontal and vertical). Measurements were carried out both on DELRIN (polyacetal plastic) and the fingertip, for a wide range of velocities (0-3 cm/s). The influence of the microvascular perfusion was evaluated by occluding the brachial artery as well as blood emptying the finger and by using a flow model. The LDF signals were correlated to the movement. In vivo measurements showed that velocities above 0.8 cm/s gave a significant contribution to the perfusion signal. Corresponding velocities for the DELRIN piece were higher (1.4 - 2.6 cm/s), and dependent on the surface structures and reflecting properties. By reducing the amount of specular reflection the movement influence was substantially lowered.© (2002) COPYRIGHT SPIE--The International Society for Optical Engineering. Downloading of the abstract is permitted for personal use only.

Galvani in Bologna revealed the electrical nature of nerve signal conduction more than two hundred years ago through the famous experiments on frog legs. All living cells are characterized by a potential across the membranes, but the nerve cells are also able to change this potential and generate electrical signals. The nerve cell, the neuron, is usually elongated into a so-called axon. An axon can conduct signals over long distances; it can for example start in the brain and end in a foot. The axon ends with a synapse, where the signal is transferred by transmitter molecules to another neuron or to an effector cell, such as a muscle cell. A puzzling feature observed to accompany the action potential conduction along the axon membrane, is a phase transition in the bilayer. This chapter provides evidence for a two-dimensional analog to a three-dimensional transition lamellar periodically curved bilayer. It demonstrates how such a transition can be induced by changes in the hydrocarbon chain packing pressure, determining the elastic properties of the bilayer. The chapter also argues that such an electro/mechanical coupling makes the action-potential more robust towards interference. The cooperative vesicle fusion at the synaptic signal transmission seems to involve a similar bilayer phase transition. Finally, the chapter considers some neurobiological phenomena, which might be related to this model, such as effects of mechanical waves on neurons.

This chapter presents a mathematical model of membranes in cell division. Cell division is of course more complicated than this, but this chapter intends to derive the mathematical machinery that works for the topological transformation of the plasma membrane. For the complete motion, it is important to derive the machinery that carries the internal structure of the cell through the transformation. Such divisions are carried out with the two kinds of lipid bilayer membranes: the single plasma membrane and the double nuclear membrane and of mitochondria. The Hermite operator is used to transfer cell content through the transformation. With mathematics for “handmade” periodicity, a mitochondrion cell is divided. The motion in a muscle cell is described mathematically. A translation operation on two single spirals has been shown to give a double of DNA-type. Mathematical mechanisms are given to form the DNA-structures of the Holliday junction, and the cruciform.

Membranes formed by lipid bilayers with embedded proteins envelope all kinds of living cells from microorganisms to the cell organization in mammals, and the organelles in the cells. The shape of the cell membranes and structural changes involved in biological processes therefore tell a lot about basic biological structures. This chapter describes cell membranes forming cubic symmetry, cubosomes. The time-averaged conformation of the lipid bilayer corresponds to nodal surfaces, reflecting the standing wave dynamics of these membranes. Cubosomes can be produced in vitro using well-defined lipids, and the experimental knowledge on these colloidal particles is derived from such lipid systems. In vivo cubosomes seem to be formed under some kind of equilibrium condition in the cell. Other three-dimensional cell membrane systems are related to cubosomes, and an example described mathematically in the chapter is that of the endoplasmatic reticulum. Periodic curvature along single membranes is analyzed, and the bilayer conformational changes involved in vesicle transport processes are derived based on standing wave dynamics.

BackgroundChildhood pre-B acute lymphoblastic leukemia (ALL) is a bone marrow (BM) derived disease, which often disseminates out of the BM cavity, where malignant cells to a variable degree can be found circulating in the peripheral blood (PB). Normal pre-B cells are absolutely dependent on BM stroma for survival and differentiation. It is not known whether transformed pre-B ALL cells retain any of this dependence, which possibly could impact on drug sensitivity or MRD measurements.ResultsPre-B ALL cells, highly purified by a novel method using surface expression of CD19 and immunoglobulin light chains, from BM and PB show a very high degree of similarity in gene expression patterns, with differential expression of vascular endothelial growth factor (VEGF) as a notable exception. In addition, the cell sorting procedure revealed that in 2 out of five investigated patients, a significant fraction of the malignant cells had matured beyond the pre-B cell stage.ConclusionThe transition of ALL cells from the BM into the circulation does not demand, or result in, major changes of gene expression pattern. This might indicate an independence of BM stroma on the part of transformed pre-B cells, which contrasts with that of their normal counterparts.