Supplemented phase diagrams for vitrification CPA cocktails: DP6, VS55 and M22.

DP6, VS55 and M22 are the most commonly used cryoprotective agent (CPA) cocktails for vitrification experiments in tissues and organs. However, complete phase diagrams for the three CPAs are often unavailable or incomplete (only available for full strength CPAs) thereby hampering optimization of vitrification and rewarming procedures. In this paper, we used differential scanning calorimetry (DSC) to measure the transition temperatures including heterogeneous nucleation temperatures (Thet), glass transition temperatures (Tg), rewarming phase crystallization (devitrification and/or recrystallization) temperatures (Td) and melting temperatures (Tm) while cooling or warming the CPA sample at 5 °C/min and plotted the obtained transition temperatures for different concentrations of CPAs into the phase diagrams. We also used cryomicroscopy cooling or warming the sample at the same rate to record the ice crystallization during the whole process, and we presented the cryomicroscopic images at the transition temperatures, which agreed with the DSC presented phenomena.

A guide to successful mL to L scale vitrification and rewarming.

Cryopreservation by vitrification to achieve an "ice free" glassy state is an effective technique for preserving biomaterials including cells, tissues, and potentially even whole organs. The major challenges in cooling to and rewarming from a vitrified state remain ice crystallization and cracking/fracture. Ice crystallization can be inhibited by the use of cryoprotective agents (CPAs), though the inhibition further depends upon the rates achieved during cooling and rewarming. The minimal rate required to prevent any ice crystallization or recrystallization/devitrification in a given CPA is called the critical cooling rate (CCR) or critical warming rate (CWR), respectively. On the other hand, physical cracking is mainly related to thermomechanical stresses, which can be avoided by maintaining temperature differences below a critical threshold. In this simplified analysis, we calculate deltaT as the largest temperature difference occurring in a system during cooling or rewarming in the brittle/glassy phase. This deltaT is then used in a simple "thermal shock equation" to estimate thermal stress within the material to decide if the material is above the yield strength and to evaluate the potential for fracture failure. In this review we aimed to understand the limits of success and failure at different length scales for cryopreservation by vitrification, due to both ice crystallization and cracking. Here we use thermal modeling to help us understand the magnitude and trajectory of these challenges as we scale the biomaterial volume for a given CPA from the milliliter to liter scale. First, we solved the governing heat transfer equations in a cylindrical geometry for three common vitrification cocktails (i.e., VS55, DP6, and M22) to estimate the cooling and warming rates during convective cooling and warming and nanowarming (volumetric heating). Second, we estimated the temperature difference deltaT and compared it to a tolerable threshold (deltaTmax) based on a simplified "thermal shock" equation for the same cooling and rewarming conditions. We found, not surprisingly, that M22 achieves vitrification more easily during convective cooling and rewarming for all volumes compared to VS55 or DP6 due to its considerably lower CCR and CWR. Further, convective rewarming (boundary rewarming) leads to larger temperature differences and smaller rates compared to nanowarming (volumetric rewarming) for all CPAs with increasing failure at larger volumes. We conclude that as more and larger systems are vitrified and rewarmed with standard CPA cocktails, this work can serve as a practical guide to successful implementation based on the characteristic length (volume/surface area) of the system and the specific conditions of cooling and warming. doi.org/10.54680/fr22610110112.

Immune Cells and Immunosenescence.

Aging is associated with progressive loss of physiological integrity, leading to impaired physical and mental functions as well as increased morbidity and mortality. With advancing age, the immune system is no longer able to adequately control autoimmunity, infections, or cancer. The abilities of the elderly to slow down undesirable effects of aging may depend on the genetic background, lifestyle, geographic region, and other presently unknown factors. Although most aspects of the immunity are constantly declining in relation to age, some features are retained, while e.g. the ability to produce high levels of cytokines, response to pathogens by increased inflammation, and imbalanced proteolytic activity are found in the elderly, and might eventually cause harm. In this context, it is important to differentiate between the effect of immunosenescence that is contributing to this decline and adaptations of the immune system that can be quickly reversed if necessary.

CD84 is markedly up-regulated in Kawasaki disease arteriopathy.

The major goals of Kawasaki disease (KD) therapy are to reduce inflammation and prevent thrombosis in the coronary arteries (CA), but some children do not respond to currently available non-specific therapies. New treatments have been difficult to develop because the molecular pathogenesis is unknown. In order to identify dysregulated gene expression in KD CA, we performed high-throughput RNA sequencing on KD and control CA, validated potentially dysregulated genes by real-time reverse transcription-polymerase chain reaction (RT-PCR) and localized protein expression by immunohistochemistry. Signalling lymphocyte activation molecule CD84 was up-regulated 16-fold (P < 0·01) in acute KD CA (within 2 months of onset) and 32-fold (P < 0·01) in chronic CA (5 months to years after onset). CD84 was localized to inflammatory cells in KD tissues. Genes associated with cellular proliferation, motility and survival were also up-regulated in KD CA, and immune activation molecules MX2 and SP140 were up-regulated in chronic KD. CD84, which facilitates immune responses and stabilizes platelet aggregates, is markedly up-regulated in KD CA in patients with acute and chronic arterial disease. We provide the first molecular evidence of dysregulated inflammatory responses persisting for months to years in CA significantly damaged by KD.

Effect of timing, dose and interstitial versus nanoparticle delivery of tumor necrosis factor alpha in combinatorial adjuvant cryosurgery treatment of ELT-3 uterine fibroid tumor.

Cryosurgery has shown potential as a minimally invasive technology for tumor treatment. However, incomplete destruction followed by tumor recurrence after cryosurgery is a common drawback. This study characterizes several variables in the cryoadjuvant TNF-alpha enhancement of conservative cryosurgery (i.e. freezing to the visible edge) of ELT-3 (uterine leiomyoma) tumor in a female nude mouse model. The variables include pretreatment time, mode of TNF-alpha delivery (native vs. CYT-6091, a PEGylated 33 nm colloidal gold core nanoparticle) and dose of TNF-alpha. Survival and tumor growth delay were measured up to 30 days and showed: 1) pretreatment with TNF-alpha required 4 hours incubation prior to cryosurgery to produce a tumor growth delay over cryosurgery alone, and 2) CYT-6091 reduced the toxicity of TNF-alpha administration over intratumoral or peritumoral injection of native TNF-alpha. Taken together, 5 microgram TNF-alpha delivered by the nanodrug CYT-6091 4 hours prior to cryosurgery yielded a dramatic reduction in tumor growth over cryosurgery alone and in some cases even total remission of the tumor. However, some toxicity at higher doses (i.e. 5 micrograms) with CYT-6091 was noted compared to previous work in prostate (LNCaP) cancer grown in a male nude mouse. Potential reasons for this, including sex and weight of the animals are discussed. Further opportunities to optimize the TNF-alpha enhanced cryosurgical response of this tumor include dosing between 2 - 5 microgram at 4 hours prior to cryosurgery, and freezing beyond the visible edge of the tumor.

Cryoinjury of MCF-7 human breast cancer cells and inhibition of post-thaw recovery using TNF-alpha.

Cryoinjury of MCF-7 human breast cancer cells and its enhancement using tumor necrosis factor-alpha (TNF-alpha) as an adjuvant, were investigated. Through a series of experiments in a two level factorial design critical parameters affecting cryotherapy responses were identified. The cryoinjury was investigated by quantifying the effects of four freeze/thaw (F/T) parameters, selected to be within the expected range for a cryosurgical iceball. Thermal parameters considered were cooling rate (5 and 50 degrees C/min), end temperature (-20 and -80 degrees C), hold time (0 and 10 min), and thawing rate (20 and 100 degrees C/min). After exposing the cells to the selected F/T conditions, survival was assessed and statistically analyzed to determine the effect of each parameter and their interactions. A statistical analysis shows that the end temperature and hold time were the two most significant parameters in the range studied. This suggests that proper control of these two parameters is important to achieve desired cryodestruction of MCF-7 cells. Enhancement of cryoinjury by TNF-alpha was also investigated in a tissue equivalent cryoinjury model in which a cryosurgical iceball is formed. MCF-7 cells cultured in a collagen matrix underwent a controlled F/T with or without TNF-alpha pre-treatment at 100 ng/ml for 24 hours. Post-thaw viability of MCF-7 cells was assessed at three hours, and at one and three days after freezing. Although the TNF-alpha treatment alone induced neither apoptotic nor necrotic cell death, the combination of TNF-alpha pre-treatment and freezing enhanced the immediate cryoinjury of MCF-7 cells, and significantly impaired the post-thaw recovery. Without TNF-alpha treatment, MCF-7 cell cultures were repopulated, reaching approximately 80% survival at day 3 even after severe cryoinjury (< or = 20% survival) at three hours. In contrast, this repopulation was significantly inhibited by TNF-alpha pre-treatment, in which case the viability of the frozen region remained below 40% at day 3. The effects of TNF-alpha on the cryoinjury of MCF-7 cells suggest that TNF-alpha may serve as a potent adjuvant to cryosurgery of breast cancer.

Use of a fluorescently labeled poly-caspase inhibitor for in vivo detection of apoptosis related to vascular-targeting agent arsenic trioxide for cancer therapy.

Arsenic trioxide (ATO, Trisenox) is a potent anti-vascular agent and significantly enhances hyperthermia and radiation response. To understand the mechanism of the anti-tumor effect in vivo we imaged the binding of a fluorescently-labeled poly-caspase inhibitor (FLIVO) in real time before and 3 h or 24 h after injection of 8 mg/kg ATO. FSaII tumors were grown in dorsal skin-fold window chambers or on the rear limb and we observed substantial poly-caspase binding associated with vascular damage induced by ATO treatment at 3 and 24 h after ATO injection. Flow cytometric analysis of cells dissociated from the imaged tumor confirmed cellular uptake and binding of the FLIVO probe. Apoptosis appears to be a major mode of cell death induced by ATO in the tumor and the use of fluorescently tagged caspase inhibitors to assess cell death in live animals appears feasible to monitor and/or confirm anti-tumor effects of therapy.

Re-purposing cryoablation: a combinatorial 'therapy' for the destruction of tissue.

It is now recognized that the tumor microenvironment creates a protective neo-tissue that isolates the tumor from the various defense strategies of the body. Evidence demonstrates that, with successive therapeutic attempts, cancer cells acquire resistance to individual treatment modalities. For example, exposure to cytotoxic drugs results in the survival of approximately 20-30% of the cancer cells as only dividing cells succumb to each toxic exposure. With follow-up treatments, each additional dose results in tumor-associated fibroblasts secreting surface-protective proteins, which enhance cancer cell resistance. Similar outcomes are reported following radiotherapy. These defensive strategies are indicative of evolved capabilities of cancer to assure successful tumor growth through well-established anti-tumor-protective adaptations. As such, successful cancer management requires the activation of multiple cellular 'kill switches' to prevent initiation of diverse protective adaptations. Thermal therapies are unique treatment modalities typically applied as monotherapies (without repetition) thereby denying cancer cells the opportunity to express defensive mutations. Further, the destructive mechanisms of action involved with cryoablation (CA) include both physical and molecular insults resulting in the disruption of multiple defensive strategies that are not cell cycle dependent and adds a damaging structural (physical) element. This review discusses the application and clinical outcomes of CA with an emphasis on the mechanisms of cell death induced by structural, metabolic, vascular and immune processes. The induction of diverse cell death cascades, resulting in the activation of apoptosis and necrosis, allows CA to be characterized as a combinatorial treatment modality. Our understanding of these mechanisms now supports adjunctive therapies that can augment cell death pathways.

Response of a liver tissue slab to a hyperosmotic sucrose boundary condition: microscale cellular and vascular level effects.

Transport of a non-permeating CPA in liver tissue was studied by experimental and theoretical techniques. The system consisted of a 20 mm x 15 mm x 500 microns (thick) slab of liver tissue which was exposed to culture media and hyperosmotic sucrose (0.3 or 0.6 M) at the boundary. The volumetric changes of cell and vascular spaces within the tissue slab at 125 microns from one of the symmetric boundaries was studied by slam freezing followed by freeze substitution microscopy. The experimental data was then theoretically investigated using two models; one based on an effective diffusion coefficient for sucrose, and another which incorporated the convective flux of water out of the cells (and the tissue) while sucrose diffuses in. We estimate the effective diffusion of sucrose as 16-33% of the actual diffusivity of sucrose in bulk water. The role of convection of water out of the tissue is against the flow of sucrose and appears to be important in reducing the effective diffusivity of the sucrose. The role of vascular compliance, porosity and tortuosity are also discussed with respect to our results.

Biophysics of freezing in liver of the freeze-tolerant wood frog, R. sylvatica.

This study investigates the water transport characteristics during freezing in the liver tissue of the freeze-tolerant wood frog Rana sylvatica. Experiments were performed using both low temperature microscopy and a differential scanning calorimeter (DSC). Tissue samples were cooled at 2 and 5 degree C/min by a "two-step" freezing technique to end temperatures of -4, -6, -8, -10, and -20 degrees C, followed by a slam cooling (> 1000 degrees C/min) step. Stereological analysis of the low temperature microscopy results leads to the conclusions that 74% of the control tissue is cellular (26% vascular), Vb (osmotically inactive cell volume) is 0.4 Vo and the Krogh cylinder dimensions are: distance between adjacent sinusoid centers, delta X = 64 microns, original sinusoid (vascular) radius, rvo = 18.4 microns and length of the Krogh cylinder, L = 0.71 microns (assuming a single isolated hepatocyte cell diameter of 16 microns). A parallel study was also done using the DSC at 2 and 5 degrees C/min, and the measured heat releases from the tissue were used to calculate water transport data. Both techniques confirmed that tissue cooled at 5 degrees C/min does not dehydrate completely, but does so when cooled at 2 degrees C/min. By curve fitting a model to 5 degrees C/min water transport data from both techniques the biophysical parameters of water transport were obtained: Lpg = 1.76 microns/min-atm and ELp = 75.5 Kcal/mol. A modified Krogh model was used to account for the fact that approximately 24% of the hepatocytes were found not to be in direct contact with the vasculature. This model was then used to explain the experimentally measured water retention in some cells on the basis of different volumetric responses to dehydration of cells directly adjacent to vascular spaces and cells at least one cell removed from the vascular spaces.

A necdin/MAGE-like gene in the chromosome 15 autism susceptibility region: expression, imprinting, and mapping of the human and mouse orthologues.

BACKGROUND: Proximal chromosome 15q is implicated in neurodevelopmental disorders including Prader-Willi and Angelman syndromes, autistic disorder and developmental abnormalities resulting from chromosomal deletions or duplications. A subset of genes in this region are subject to genomic imprinting, the expression of the gene from only one parental allele. RESULTS: We have now identified the NDNL2 (also known as MAGE-G) gene within the 15q autistic disorder susceptibility region and have mapped its murine homolog to the region of conserved synteny near necdin (Ndn) on mouse Chr 7. NDNL2/MAGE-G is a member of a large gene family that includes the X-linked MAGE cluster, MAGED1 (NRAGE), MAGEL2 and NDN, where the latter two genes are implicated in Prader-Willi syndrome. We have now determined that NDNL2/Ndnl2 is widely expressed in mouse and human fetal and adult tissues, and that it is apparently not subject to genomic imprinting by the PWS/AS Imprinting Center. CONCLUSION: Although NDNL2/MAGE-G in the broadly defined chromosome 15 autistic disorder susceptibility region, it is not likely to be pathogenic based on its wide expression pattern and lack of imprinted expression.

Evaluation of thermal therapy in a prostate cancer model using a wet electrode radiofrequency probe.

PURPOSE: To determine the temperature-time threshold of local cell death in vivo for thermal therapy in a prostate cancer animal model and to use this value as a benchmark to quantify global tissue injury. MATERIALS AND METHODS: Two studies were designed in the Dunning AT-1 rat prostate tumor hind limb model. For both studies, a wet electrode radiofrequency (RF) probe was used to deliver 40 W of energy for 18 to 62 seconds after a 30-second infusion of hypertonic saline/Hypaque through the RF antenna. Thermal history measurements were obtained in tumors from at least two Fluoroptic probes placed radially 5 mm from the axis of a RF probe and 10 mm below the surface of the tissue. In study 1, the thermal history required for irreversible cell injury was experimentally determined by comparing the predicted injury accumulation (omega) with cell viability at the fluoroptic probe locations using an in vivo-in vitro assay. The omega value was calculated from the measured thermal histories using an Arrhenius damage model. In study 2, RF energy was applied for 40 seconds in all cases. At 1, 3, and 7 days after thermal therapy, triphenyltetrazolium chloride dye (TTC) and histologic analyses were performed to assess global tissue injury within a 5-mm radius from the axis of the RF probe. RESULTS: Study 1 showed that cell survival dropped to 0 for 0.42 < omega < 0.7. This result was the basis for selection of 40 seconds of RF thermal therapy in study 2, which yielded omegaave = 0.5 in the tissue 5 mm from the probe axis. Both TTC and histology analysis showed that sham-treated tissue was not irreversibly injured. However, there was an inherent heterogeneity present in the tumor that accounted for as much as 15% necrosis in control or sham-treated tissue. In contrast, at 1, 3, and 7 days after therapy, significantly less enzyme activity was observed by TCC in thermally treated tissue compared with sham-treated tissue (35 v 85%; P < 0.001). Histologic analysis of thermally treated tissues revealed a gradual increase in the percent of coagulative necrosis (47%-70%) with a concomitant decrease in the percentage of shocked cells (53%-28%). At day 7, <3% viability was observed in treated tumors compared with 90% viability in sham-treated tissue. CONCLUSION: The threshold of cellular injury in vivo corresponded to omega > 0.7 (> or =48 degrees C for 40 seconds). Global tissue injury could be conservatively predicted on the basis of local thermal histories during therapy.

Measurement and prediction of thermal behavior and acute assessment of injury in a pig model of renal cryosurgery.

PURPOSE: To analyze in vivo end temperatures and histologic injury in a standardized cryo-iceball using a porcine kidney model in order to establish the threshold temperature for tissue ablation. To evaluate the ability to predict end temperatures using a thermal finite element model. MATERIALS AND METHODS: A single freeze/thaw cryolesion was created in five pig kidneys and the temperature history recorded. End temperature was calculated using a thermal finite element model. The threshold temperature for tissue injury was established by directly correlating end temperature and histologic injury. RESULTS: Reproducible geometry and temperature profiles of the cryo-iceball were found. End temperature could be accurately predicted through thermal modeling, and correlation with histologic injury revealed a threshold temperature of -16.1 degrees C for complete tissue ablation. CONCLUSION: Thermal modeling may accurately predict end temperature within a cryo-iceball. Provided threshold temperatures for tissue destruction are known, modeling may become a powerful tool in cryosurgery, improving the assessment of damage in normal and malignant tissue.

Ice formation in isolated human hepatocytes and human liver tissue.

Cryopreservation of isolated cells and tissue slices of human liver is required to furnish extracorporeal bioartificial liver devices with a ready supply of hepatocytes, and to create in vitro drug metabolism and toxicity models. Although both the bioartificial liver and many current biotoxicity models are based on reconstructing organ functions from single isolated hepatocytes, tissue slices offer an in vitro system that may more closely resemble the in vivo situation of the cells because of cell-cell and cell-extracellular matrix interactions. However, successful cryopreservation of both cellular and tissue level systems requires an increased understanding of the fundamental mechanisms involved in the response of the liver and its cells to freezing stress. This study investigates the biophysical mechanisms of water transport and intracellular ice formation during freezing in both isolated human hepatocytes and whole liver tissue. The effects of cooling rate on individual cells were measured using a cryomicroscope. Biophysical parameters governing water transport (Lpg = 2.8 microns/min-atm and ELp = 79 kcal/mole) and intracellular heterogeneous ice nucleation (omega het = 1.08 x 10(9) m-2s-1 and kappa het = 1.04 x 10(9) K5) were determined. These parameters were then incorporated into a theoretical Krogh cylinder model developed to simulate water transport and ice formation in intact liver tissue. Model simulations indicated that the cellular compartment of the Krogh model maintained more water than isolated cells under the same freezing conditions. As a result, intracellular ice nucleation occurred at lower cooling rates in the Krogh model than in isolated cells. Furthermore, very rapid cooling rates (1000 degrees C/min) showed a depression of heterogeneous nucleation and a shift toward homogeneous nucleation. The results of this study are in qualitative agreement with the findings of a previous experimental study of the response to freezing of intact human liver.

Evaluation of freezing effects on human microvascular-endothelial cells (HMEC).

There is mounting evidence that the endothelium may play an important role in traditional cryosurgical treatments by acting to locally foster thrombi in the microvasculature of various tissues after freezing. In addition, new catheter based cryosurgical probes are being designed for cardiovascular applications where endothelial and smooth muscle cell freezing is involved but not well understood. Therefore, this study was designed to investigate, at the cellular level in human microvascular endothelial cells (hMEC), the various biophysical changes that occur during freezing which can affect post-freeze viability. The hMECs were loaded on a cryomicroscope stage and freezing experiments at 5, 10, 15, 25, 100 and 130 degrees C/min were performed to experimentally evaluate dehydration (water transport) as well as intracellular ice formation (IIF) within this cell system. The dehydration kinetics at 5, 10 and 25 degrees C/min were found to be governed by a membrane permeability L(pg) and activation energy E(Lp) of 0.05 (microm/min.atm) and 14.8 (kcal/mole) respectively [R(2)=0.94]. These parameters were then tested for predictive ability against the experimentally measured behavior at 15 degrees C/min with a good agreement [R(2)=0.98]. Intracellular Ice Formation (IIF) was found to occur at lower temperatures than many cell types (i.e. TIIF 50% approximately -18 degrees C) and at cooling rates greater than or equal to 25 degrees C/min. At cooling rates above 50 degrees C/min, two types of IIF, cell darkening and twitching, were both observed and quantified and were assumed to be governed by Surface Catalyzed Nucleation (SCN). IIF parameters, omega(o) and kappa(o), which fit data from 50, 100 and 130 degrees C/min were found to be 6.8 x 10(-8) (m(2).s)(-1) and 8.3 x 10(-9) (K5) [R(2)=0.94] respectively. Preliminary results show that viability drops precipitously between -20 and -30 degrees C, however, further studies are warranted to address the role of cooling rate, end-temperature, hold time and thawing rate to establish the freeze sensitivity of this cell.

[Reliability, trainability and stability of auditory discrimination performance in 2 computer-assisted assessment and training methods]. / Reliabilität, Trainierbarkeit und Stabilität auditiv diskriminativer Leistungen bei zwei computergestützten Mess- und Trainingsverfahren.

OBJECTIVES: The present study focuses on the possibilities and effects of training dyslexic children in tone and phoneme discrimination tasks. METHODS: A computer program was developed to train dyslexic children to discriminate between tone and speech stimuli. The correlation between auditory discrimination and reading and orthography performance was then tested in a preliminary study of n = 63 children. In a prospective study 44 children were assigned to one of three paralyzed groups: tone training, phoneme training or a control group. Upon completion of the initial diagnostics for all groups, the two training groups received four weeks of discrimination training, after which all three groups were immediately re-tested for the first time. Parallel thereto all children underwent specific training in reading and orthography at their school. Six months later all were re-tested a second time. RESULTS: Both test methods showed a high reliability (rn = .94; .95). Significant correlations between auditory discrimination and reading and orthography performance were confirmed. Auditory discrimination was significantly trainable. Specific training effects, as well as independent developmental effects were found. While the training effects of phoneme discrimination were stable over six months, those of tone discrimination were not. CONCLUSION: The central auditory discrimination between tone and phoneme stimuli can be trained successfully in dyslexic children and might also affect their reading and orthography performance.

[Prevalence of the metabolic syndrome and its risk factors: results of a large work-site health assessment]. / Prävalenz des Metabolischen Syndroms und seiner Risikofaktoren: Ergebnisse einer großen betrieblichen Gesundheitsuntersuchung.

BACKGROUND: Facing the demographic change, cardiovascular risk factors have been assessed within an occupational checkup to establish health programs. PATIENTS AND METHODS: From 2006 to 2007, anthropometric and blood parameters of 27 359 employees of a large company of the German automobile industry were collected aiming to determine the prevalence of metabolic syndrome (by NCEP ATP III) and its risk factors. Data from 3048 employees (fasting state) were analyzed (age: ∅ 39,4 ± 10,3 years, 81.4% males). RESULTS: The most common risk factors were hypertension ≥ 130/85 mmHg (men [m]: 74,4%, 95%-confidence interval [CI] 73-76%, women [w]: 47,1%, 95%-CI 43-51%), elevated triglycerides (≥ 150 mg/dl; m: 32,8%, 95%-CI 31-35%, w: 13,8%, 95%-CI 11-17%) and waist-circumferences (> 102 cm for men: 15,1%, 95%-CI 14-17%; > 88 cm for women: 16,9%, 95%-CI 14-20%). The prevalence of metabolic syndrome (≥ 3 risk factors) was 11,7% (95%-CI 12-15%; m: 12,7%, 95%-CI 11-14%, w: 7,4%, 95%-CI 6-10%) increasing with physical inactivity and rising age up to 20%. The prevalence of hypertension in young (< 20 years) and elder men (≥ 50 years) was similarly high (79,1%, 95%-CI 70-86% vs. 79,9%, 95%-CI 75-82%). CONCLUSION: The prevalence of metabolic syndrome in this sample is rather low, but 75% of the men and nearly 50% of the women had hypertension. Health programs should focus on this risk factor in particular.

Optimizing magnetic nanoparticle based thermal therapies within the physical limits of heating.

Magnetic nanoparticle (mNP) based thermal therapies have demonstrated relevance in the clinic, but effective application requires an understanding of both its strengths and limitations. This study explores two critical limitations for clinical use: (1) maximizing localized mNP heating, while avoiding bulk heating due to inductive coupling of the applied field with the body and (2) the limits of treatable volumes, related to basic heat transfer. Two commercially available mNPs are investigated, one superparamagnetic and one ferromagnetic, thereby allowing a comparison between the two fundamental types of mNPs (both of which are being evaluated for clinical use). Important results indicate that in dispersed solutions, the superparamagnetic mNPs outperform on a per mass basis (2× better), but the ferromagnetic mNPs outperform on a per nanoparticle basis (170× better), at the fields of highest clinical relevance (approximately 100 kHz and 20 kA/m). We also demonstrate a new method of observing heating in microliter droplets of mNP solution, leading to scaling analyses that suggest treatable tumor volumes should be ≥2 mm in diameter (for mNP loading of ≥10 mg Fe/g tumor), to achieve therapeutic temperatures ≥43 °C. This technique also provides a novel platform for quantifying heating from microgram quantities of mNPs.

Whole-body MRI and MRA for evaluation of the prevalence of atherosclerosis in a cohort of subjectively healthy individuals.

OBJECTIVES: To assess the prevalence of cardiovascular findings in asymptomatic individuals by means of 1.5-T whole-body magnetic resonance imaging and angiography. METHODS: A cohort of 138 individuals (118 men, 20 women) with a mean age of 54 years (SD ± 7.55) was referred to whole-body MRI at 1.5-T, including contrast-enhanced whole-body MR angiography (MRA) and cardiac MRI. A total of 2,065/2,070 vessel segments (99.8%) and cardiac function were evaluated. RESULTS: Approximately one-fourth of the participating individuals had vascular abnormalities. In 17 subjects (12.3% of all subjects) significant luminal narrowing was observed in at least one vascular segment. Luminal narrowing (mild to severe) was observed in 1 (0.7% of all subjects respectively) of the renal arteries, 7 (5.0%) of the carotid arteries, and 3 (2.2%) of the pelvic and upper leg arteries, and in 17 segments (12.3%) of arteries in the lower leg. In cardiac function and perfusion imaging, wall motion disorders were observed in six patients (4.3%), with additional delayed enhancement and isolated delayed enhancement present in two cases. Functional parameters differed from reference values in 55 cases. CONCLUSIONS: Even in an asymptomatic cohort of middle-aged predominantly male individuals, atherosclerotic disease is not uncommon and is detectable by whole-body MRI. MAIN MESSAGES: • In middle-aged predominantly male individuals, atherosclerotic disease is not uncommon. • Even in an asymptomatic collective, approximately one fourth had vascular abnormalities. • Using whole-body MR angiography (MRA), 99.8% of 2,070 vessel segments could be evaluated.