Application of a novel microscopic technique for quantifying CA125 binding to circulating mononuclear cells in longitudinal specimens during treatment for ovarian cancer.

BACKGROUND: Measurement of serum CA125, an antigenic fragment of human mucin 16 (MUC16), is used to monitor the clinical progression of epithelial ovarian cancer (EOC). However, rather than simply a passive marker reflecting tumor burden, MUC16 may have a more active role by binding to immune cells and altering their tumor response. We developed a research tool to measure MUC16-binding to the surfaces of peripheral blood mononuclear cell (PBMC) subtypes and tested its research value using specimens collected serially from a woman being treated for high grade serous EOC. METHODS: Cryopreserved PBMCs were mixed with anti-CA125 antibody-labeled plasmonic gold nanoparticles (PNPs) to detect cell surface MUC16-binding along with fluorescent stains to identify B cells, NK cells, NK-T cells, T cells, and monocytes. From 3D darkfield images, a computer algorithm was applied to enumerate PNP-binding and fluorescence microscopy to identify cell lineage. Average MUC16-binding was determined by fitting a Poisson distribution to PNP-counts across similar cell types. MUC16-binding to cell types was correlated with treatment details, CA125 levels, and complete blood count (CBC) data. RESULTS: Over a 21-month period, monocytes had the highest level of MUC16-binding which was positively correlated with serum CA125 and inversely correlated with circulating monocyte and lymphocyte counts. Fluctuations of PNP-binding to NK cells were associated temporally with types of chemotherapy and surgical events. Levels of MUC16 bound to NK cells were positively correlated with levels of MUC16 bound to T and NK-T cells and inversely correlated with circulating platelets. CONCLUSIONS: Assessment of MUC16-binding among cryopreserved PBMC cell types can be accomplished using darkfield and fluorescence microscopy. Correlations observed between level of binding by cell type with serum CA125, CBC data, and treatment details suggest that the new techniques may offer novel insights into EOC's clinical course.

Protective effect of glutathione S-transferase enzyme activity against aflatoxin B1 in poultry species: relationship between glutathione S-transferase enzyme kinetic parameters, and resistance to aflatoxin B1.

Comparative studies designed to investigate the role of glutathione S-transferase (GST) activity on the enzyme catalyzed trapping of aflatoxin B1-8,9-epoxide (AFBO) with glutathione, and the relationship with aflatoxin B1 (AFB1) resistance have not been conducted in poultry. Hepatic cytosolic fractions of chickens, quail, turkeys and ducks were used to measure in vitro the enzymatic parameters maximal velocity (Vmax), Michaelis-Menten constant (Km) and intrinsic clearance (CLint) for GST activity. AFB1 used ranged from 2.0 to 157.5 µM and the AFB1-GSH produced was identified and quantitated by HPLC. Significant differences were found in GST Vmax values, being the highest in chickens, followed by quail, ducks and turkeys. The Km values were also significantly different, with chickens < ducks < turkeys < quail. Chickens had the higher CLint value in contrast to ducks. Differences by sex showed that duck females had a higher CLint value than the turkey and quail, whereas duck males had a CLint close to that of turkey. The ratio "AFBO production /AFB1-GSH production" follows the order duck>turkey>quail>chicken, in agreement with the known poultry sensitivity. The extremely high "AFB1 epoxidation activity/ GST activity" ratio observed in ducks might be the explanation for the development of hepatocellular carcinoma in this species.

Characterization of Cell-Bound CA125 on Immune Cell Subtypes of Ovarian Cancer Patients Using a Novel Imaging Platform.

MUC16, a sialomucin that contains the ovarian cancer biomarker CA125, binds at low abundance to leucocytes via the immune receptor, Siglec-9. Conventional fluorescence-based imaging techniques lack the sensitivity to assess this low-abundance event, prompting us to develop a novel "digital" optical cytometry technique for qualitative and quantitative assessment of CA125 binding to peripheral blood mononuclear cells (PBMC). Plasmonic nanoparticle labeled detection antibody allows assessment of CA125 at the near-single molecule level when bound to specific immune cell lineages that are simultaneously identified using multiparameter fluorescence imaging. Image analysis and deep learning were used to quantify CA125 per each cell lineage. PBMC from treatment naïve ovarian cancer patients (N = 14) showed higher cell surface abundance of CA125 on the aggregate PBMC population as well as on NK (p = 0.013), T (p < 0.001) and B cells (p = 0.024) compared to circulating lymphocytes of healthy donors (N = 7). Differences in CA125 binding to monocytes or NK-T cells between the two cohorts were not significant. There was no correlation between the PBMC-bound and serum levels of CA125, suggesting that these two compartments are not in stoichiometric equilibrium. Understanding where and how subset-specific cell-bound surface CA125 takes place may provide guidance towards a new diagnostic biomarker in ovarian cancer.

Plasmonic Nanoparticle-Based Digital Cytometry to Quantify MUC16 Binding on the Surface of Leukocytes in Ovarian Cancer.

Although levels of the circulating ovarian cancer marker (CA125) can distinguish ovarian masses that are likely to be malignant and correlate with severity of disease, serum CA125 has not proved useful in general population screening. Recently, cell culture studies have indicated that MUC16 may bind to the Siglec-9 receptor on natural killer (NK) cells where it downregulates the cytotoxicity of NK cells, allowing ovarian cancer cells to evade immune surveillance. We present evidence that the presence of MUC16 can be locally visualized and imaged on the surface of peripheral blood mononuclear cells (PBMCs) in ovarian cancer via a novel "digital" cytometry technique that incorporates: (i) OC125 monoclonal antibody-conjugated gold nanoparticles as optical nanoprobes, (ii) a high contrast dark-field microscopy system to detect PBMC-bound gold nanoparticles, and (iii) a computational algorithm for automatic counting of these nanoparticles to estimate the quantity of surface-bound MUC16. The quantitative detection of our technique was successfully demonstrated by discriminating clones of the ovarian cancer cell line, OVCAR3, based on low, intermediate, and high expression levels of MUC16. Additionally, PBMC surface-bound MUC16 was tracked in an ovarian cancer patient over a 17 month period; the results suggest that the binding of MUC16 on the surface of immune cells may play an early indicator for recurrent metastasis 6 months before computational tomography-based clinical diagnosis. We also demonstrate that the levels of surface-bound MUC16 on PBMCs from five ovarian cancer patients were greater than those from five healthy controls.

In vitro hepatic aflatoxicol production is related to a higher resistance to aflatoxin B1 in poultry.

A study was conducted to determine the cytosolic in vitro hepatic enzymatic kinetic parameters Vmax, KM, and intrinsic clearance (CLint) for aflatoxin B1 (AFB1) reductase [aflatoxicol (AFL) production] and AFL dehydrogenase (AFB1 production) in four commercial poultry species (chicken, quail, turkey and duck). Large differences were found in AFB1 reductase activity, being the chicken the most efficient producer of AFL (highest CLint value). Oxidation of AFL to AFB1 showed only slight differences among the different poultry species. On average all species produced AFB1 from AFL at a similar rate, except for the turkey which produced AFB1 from AFL at a significantly lower rate than chickens and quail, but not ducks. Although the turkey and duck showed differences in AFL oxidation Vmax and KM parameters, their CLint values did not differ significantly. The ratio AFB1 reductase/AFL dehydrogenase enzyme activity was inversely related to the known in vivo sensitivity to AFB1 being highest for the chicken, lowest for the duck and intermediate for turkeys and quail. Since there is no evidence that AFL is a toxic metabolite of AFB1, these results suggest that AFL production is a detoxication reaction in poultry. Conversion of AFB1 to AFL prevents the formation of the AFB1-8,9-exo-epoxide which, upon conversion to AFB1-dihydrodiol, is considered to be the metabolite responsible for the acute toxic effects of AFB1.

An unusually high production of hepatic aflatoxin B1-dihydrodiol, the possible explanation for the high susceptibility of ducks to aflatoxin B1.

A study was conducted to determine the enzymatic kinetic parameters Vmax, KM, and intrinsic clearance (CLint) for the hepatic in vitro production of aflatoxin B1-dihydrodiol (AFB1-dhd) from aflatoxin B1 (AFB1) in four commercial poultry species, ranging in sensitivity to AFB1 from highest (ducks) to lowest (chickens). Significant but small differences were seen for Vmax, while large significant differences were observed for KM. However, the largest inter-species differences were observed for the CLint parameter, with ducks being extraordinarily efficient in converting AFB1 into AFB1-dhd. Since AFB1-dhd is considered the metabolite responsible for the acute toxic effects of AFB1, the high hepatic production of AFB1-dhd from AFB1 in ducks is the possible biochemical explanation for the extraordinary high sensitivity of this poultry species to the adverse effects of AFB1.

Immunophenotyping of cerebrospinal fluid cells in ischaemic stroke.

BACKGROUND AND PURPOSE: Post-ischaemic immune cell invasion into the brain is well characterized in animal stroke models and contributes to neuronal damage. Therefore, it represents a promising therapeutic target. Cerebrospinal fluid (CSF) is easily accessible and may reflect cellular events within the parenchyma. However, comprehensive studies on CSF immune cells in patients with stroke are lacking. METHODS: In a retrospective cohort study, we performed extensive immune-cell profiling in CSF and peripheral blood of patients with acute ischaemic stroke and healthy controls. In patients with stroke, infarct size was quantified on follow-up imaging. RESULTS: Overall, 90 patients with ischaemic stroke and 22 controls were included in our study. After stroke, the total protein was increased (537.3 vs. 353.2 mg/L, P = 0.008) and the mean total white cell count was slightly but non-significantly elevated (1.76 vs. 0.50 cells/µL, P = 0.059). Proportions of CSF lymphocytes, monocytes and granulocytes and their respective subsets did not differ between patients with stroke and controls. In addition, there were no associations between proportions of major leukocyte subsets in CSF and the time from symptom onset to CSF sampling, infarct size or infarct localization. CONCLUSIONS: Ischaemic stroke induces only a very slight increase of CSF immune cells without changes in the composition of immune cell subsets, thus indicating that parenchymal inflammation is not sufficiently reflected in the CSF. Our findings suggest that CSF is not a major invasion route for immune cells and that CSF cell analyses are not suitable as biomarkers to guide future immune therapies for stroke.

IL-10 downregulates CXCR3 expression on Th1 cells and interferes with their migration to intestinal inflammatory sites.

Inflammatory bowel disease (IBD) is characterized by chronic, uncontrolled inflammation in the intestinal mucosa. Although the etiology is poorly understood, it is widely accepted that loss of tolerance is involved in the development of IBD. Therefore, re-establishing tolerance or gut homeostasis is one of the key features in the development of new therapeutic strategies. Here we show that antigen targeting to DEC-205 on dendritic cells leads to an interleukin (IL)-10-dependent downregulation of C-X-C chemokine receptor 3 (CXCR3) expression on differentiated antigen-specific T helper type 1 (Th1) cells in vivo. This downregulation interferes with the migration of Th1 cells into the gut and protects mice against severe acute and relapsing intestinal inflammation. Moreover, CD4(+)CXCR3(+) T cells are highly enriched in the inflamed mucosa of IBD patients. Interference with this pathway may therefore be a promising approach for the treatment of IBD. In conclusion, we propose a hitherto undescribed mechanism by which IL-10 can act on effector T cells and orchestrate intestinal immune responses.

Versatile atomic force microscopy setup combined with micro-focused X-ray beam.

Micro-focused X-ray beams produced by third generation synchrotron sources offer new perspective of studying strains and processes at nanoscale. Atomic force microscope setup combined with a micro-focused synchrotron beam allows precise positioning and nanomanipulation of nanostructures under illumination. In this paper, we report on integration of a portable commercial atomic force microscope setup into a hard X-ray synchrotron beamline. Details of design, sample alignment procedure, and performance of the setup are presented.

Impact of same-day antibiotic susceptibility testing on time to appropriate antibiotic treatment of patients with bacteraemia: a randomised controlled trial.

Inadequate therapy in bloodstream infections is suggested to be associated with higher mortality. We evaluated the reduction in inappropriate antibiotic therapy using rapid identification and antibiotic susceptibility testing (FAST) compared to standard of care (SOC) testing in patients with bloodstream infections. The FAST method used polymerase chain reaction (PCR) for identification and to detect growth in the presence or absence of antibiotics after only 6 h. For SOC testing, the BD Phoenix system was used. Patients with blood cultures growing Staphylococcus, Streptococcus or Enterococcus species or Gram-negative rods were randomised for FAST or SOC tests. A total of 129 patients were randomised for FAST and 121 patients for the SOC group. At the time SOC results became available, 78 patients in the FAST group could have been switched to more appropriate therapy. Although FAST results were highly accurate (agreement with SOC was 94%), they were only implemented in a minority (16) of patients. However, significantly fewer patients in the FAST group used inappropriate therapy at the time of SOC results (p = 0.025). The time to results in the FAST group was reduced by 15.6 h (p < 0.001). In the patients switched after FAST, this was done after a mean of 42.3 h compared to 61.4 h in those switched after SOC tests (p < 0.001). In bacteraemic patients, FAST resulted in significantly more patients using appropriate antibiotic therapy at the time SOC results were available and 15.6 h earlier than SOC tests. However, the implementation of FAST results was not optimal and no benefit on clinical outcome was shown.

[Not like toilet reading- C. W. Hufeland and his publisher Brockhaus]. / Nicht wie eine Toiletten-Lektüre - C. W. Hufeland und sein Verleger Brockhaus.

This is to remember Christoph Wilhelm Hufeland (1762-1836) who at his time was one of the most influential German physicians and whose ideas are living even nowadays. Three letters to Brockhaus that have been found recently document an ambivalent attitude towards this publisher.

Vertically stacked quantum dot pairs fabricated by nanohole filling.

Strain-free, vertically coupled GaAs quantum dots (QDs) with an ultra-low density below 1 × 10(7) cm(-2) are fabricated by filling of self-assembled nanoholes with a GaAs/AlGaAs/GaAs layer sequence. The sizes of the two QDs, forming a QD pair (QDP), as well as the AlGaAs tunnel-barrier between the dots are tuned independently. We present atomic force microscopy studies of the QDP formation steps. We have performed photoluminescence studies of single QDPs with varied dot size and tunnel-barrier thickness. The data indicate non-resonant tunnelling between the dots. Furthermore, we apply the quantum confined Stark effect to tune the photoluminescence energy by up to 25 meV.

Comparison of peripartum metabolic status and postpartum health of Holstein and Montbéliarde-sired crossbred dairy cows.

Objectives of the current experiment were to evaluate plasma concentrations of metabolites and haptoglobin peripartum, uterine health and involution, and follicle growth and resumption of cyclicity of Holstein (HO) and Montbéliarde-sired crossbred cows. Cows (52 HO and 52 crossbred) were enrolled in the study 45 d before expected calving date. Cows had body weight and body condition score recorded on d -45, -14, 0, 1, 28, and 56 relative to calving. Dry matter intake was calculated for a subgroup of cows (25 HO and 38 crossbred) from 6 wk before to 6 wk after calving. Blood was sampled weekly from d -14 to 56 relative to calving for determination of glucose, nonesterified fatty acid, and ß-hydroxybutyrate concentrations; from d -7 to 21 relative to calving for determination of haptoglobin concentration; and from d 14 to 56 postpartum for determination of progesterone concentration. Cows were examined at calving and on d 4, 7, 10, and 14 postpartum for diagnosis of postparturient diseases, on d 24 postpartum for diagnosis of purulent vaginal discharge, and on d 42 postpartum for diagnosis of subclinical endometritis. Uteri and ovaries were examined by ultrasonography every 3 d from d 14 to 41 postpartum. Milk yield and composition were measured monthly and yield of milk, fat, protein, and energy-corrected milk were recorded for the first 90 d postpartum. Body weight was not different between Holstein and crossbred cows, but HO cows had reduced body condition score compared with crossbred cows. Even though DMI from 6 wk before to 6 wk after calving tended to be greater for HO cows (16.8 ± 0.7 vs. 15.3 ± 0.5 kg/d), HO cows tended to have more pronounced decline in dry matter intake, expressed in percentage of body weight from d -15 to 0 relative to calving. Energy-corrected milk and nonesterified fatty acid and ß-hydroxybutyrate concentrations were not different between breeds. No differences were observed in incidence of retained fetal membranes, metritis, and subclinical endometritis, but HO cows tended to be more likely to have pyrexia from d 0 to 15 postpartum (50.0 vs. 31.4%) and to have greater incidence of purulent vaginal discharge (44.2 vs. 26.5%) than crossbred cows. Holstein cows were more likely to have at least 1 uterine disorder postpartum than crossbred cows (63.5 vs. 36.7%). No differences between breeds were observed in uterine involution. Holstein cows had larger subordinate follicles (10.1 ± 0.4 vs. 8.9 ± 0.5) and a greater number of class III follicles (1.6 ± 0.1 vs. 1.2 ± 0.1) than crossbred cows. Furthermore, the first corpus luteum postpartum of HO cows was diagnosed at a slower rate compared with crossbred cows. Crossbred cows had improved uterine health compared with HO cows and this may have been a consequence of heterosis and (or) breed complementarity and less pronounced decrease in DMI during the last days of gestation.

[Remembering Ismar Boas (1858 - 1938)]. / Erinnerung an Ismar Boas (1858 - 1938).

Ismar Boas is revered as one of the pioneers of modern gastroenterology. 75 years after his suicide due to Nazism it is appropriate to remember the great clinician and scientist. Moreover in a newly detected report from his hands some information on his thinking and handling of medical problems can be derived and his view of medial progress until today can be assessed.

Effects of prepartum controlled-energy wheat straw and grass hay diets supplemented with starch or sugar on periparturient dairy cow performance and lipid metabolism.

This study examined the effects of a forage source [wheat straw (WS) versus grass hay (GH)] prepartum and supplemental carbohydrate source [corn (dry feed; DF) versus molasses (liquid feed; LF)] on pre- and postpartum intake, digestibility, selective particle consumption, milk yield, and lipid metabolism. The objectives were to determine if forage or pre- and postpartum supplement alters periparturient intake, energy balance, and milk yield. Sixty (n=15) multiparous dairy cows were used in a randomized complete block design with a 2 × 2 factorial arrangement of treatments to compare WS versus GH diets supplemented with either DF or LF. Dietary treatments were (1) WS prepartum + DF pre- and postpartum (WSDF), 2) WS prepartum + LF pre- and postpartum (WSLF), (3) GH prepartum + DF pre- and postpartum (GHDF), and (4) GH prepartum + LF pre- and postpartum (GHLF). Treatments began at dry-off, × before expected calving. During the prepartum phase, cows maintained dry matter intake (DMI) at 2.0% of body weight and prepartum energy balance remained positive for all treatments until calving. Prepartum GH diets had a more positive energy balance compared with WS diets. On week -5, energy balance was more positive for GHDF than for WSDF or GHLF. Energy balance for WSLF, however, was lower on week -3 and -1 than GHDF. Liquid feed decreased dry matter digestibility and increased prepartum liver triglyceride, serum nonesterified fatty acids (NEFA), and tended to increase ß-hydroxybutyrate. After calving, LF decreased DMI and energy balance, but not yield of milk or 3.5% fat-corrected milk, resulting in greater feed efficiency compared with DF. Forage did not affect postpartum DMI, but milk yield tended to be higher for WS versus GH. The DMI expressed as percentage of body weight was not affected by supplement or prepartum forage type. Cows fed WS had lower serum NEFA, higher liver glycogen, and tended to have a lower triglyceride to glycogen ratio postpartum than GH. Serum NEFA peaked on d 14 for all treatments and then declined thereafter. In postpartum diets, more particles were retained on the top screen for LF (>19.0mm) of the Penn State Particle Separator, which also tended to have more particles in the second screen (particles 19.0-8.0mm). Supplement had minimal effect on postpartum selective particle consumption. In conclusion, feeding diets containing WS resulted in lower postpartum serum NEFA, higher liver glycogen, and a tendency for greater milk production and lower liver triglyceride to glycogen than those containing GH. Liquid feed reduced postpartum DMI but not yield of milk yield or 3.5% fat-corrected milk yield, resulting in an improvement in feed efficiency. Future research should continue to investigate the use of single dry cow diet feeding strategies as they affect pre- and postpartum animal responses.

Effects of feeding wheat straw or orchardgrass at ad libitum or restricted intake during the dry period on postpartum performance and lipid metabolism.

The objectives of this study were to investigate the effects of forage source [wheat straw (WS) or orchardgrass hay (OG)] and total amount of diet dry matter fed [ad libitum or restricted to 70% of predicted dry matter intake (DMI)] prepartum on postpartum performance. The study design was a 2×2 factorial design with 10 cows per treatment. Treatments were WS total mixed ration (TMR) ad libitum, OG TMR ad libitum, WS TMR restricted, and OG TMR restricted. The WS TMR (dry matter basis) contained 30% WS, 20.7% corn silage, 10.0% alfalfa hay, 18.2% ground corn, 16.8% soybean meal, and 4.3% molasses mineral mix (14.7% CP, 1.5 Mcal/kg of net energy for lactation, 37.0% neutral detergent fiber). The OG TMR contained 30% OG, 46.2% corn silage, 10.0% alfalfa hay, 9.5% soybean meal, and 4.3% molasses (14.2% CP, 1.5 Mcal/kg of net energy for lactation, 41.0% neutral detergent fiber). Cows received 1 lactation diet after calving (17.7% CP, 1.6 Mcal/kg of net energy for lactation, 27.3% neutral detergent fiber). Total diet DMI prepartum was higher for ad libitum than for restricted as designed, but forage source had no effect on DMI. Total tract apparent digestibilities of DM and NDF were greater for OG than for WS. Postpartum DMI expressed as a percentage of body weight for the first week of lactation was higher for ad libitum than for restricted diets. Postpartum DMI during the first 30 d of lactation was higher for OG than for WS, but no effect was observed for the amount fed prepartum. Milk yield during the first week of lactation was higher for OG than for WS; however, during the first 30 d, 3.5% fat-corrected milk yield and yield of milk fat were highest for OG TMR restricted and WS TMR ad libitum. Prepartum treatments had a limited effect on pre- and postpartum lipid metabolism; however, cows fed WS TMR ad libitum had the highest postpartum ß-hydroxybutyrate. Eating behavior was observed by 10-min video scans of 24-h video surveillance for 5d pre- and postpartum. Prepartum eating time and eating bouts tended to be greater by WS than for OG, and postpartum eating time per kilogram of neutral detergent fiber intake tended to be greater for WS than for OG. Results indicate that forage source and amount of DM fed prepartum affected postpartum performance and tended to alter the behavior of cows in tie-stall barns.

[Comments on the Guidelines for the Prudent Use of Antibacterial Veterinary Pharmaceuticals (Guidelines for Antibiotics)]. / Anmerkungen zu den "Leitlinien für den sorgfältigen Umgang mit antimikrobiell wirksamen Tierarzneimitteln" (Antibiotika-Leitlinien).

In 2010 the German Bundestierärztekammer (Federal Chamber of Veterinarians) and the AGTAM (Working Group "Veterinary Pharmaceuticals") published the Guidelines for the prudent use of antibacterial veterinary pharmaceuticals in an updated version. Within the limits of therapeutic freedom, veterinarians are committed to take into account the latest scientific findings in veterinary medicine. These findings may, however, include conflicting interpretations if such an approach is expressed by an accredited university or anywhere else in the field of science. Hence, the state of science in veterinary medicine is not only defined by the Guidelines for Antibiotics, rather, the complete recognized scientific literature has to be considered. The Guidelines for Antibiotics are not legally-binding rules. They define the best approach and not the minimum standard for the use of antibiotics. The clinical examination provides the basis for medical treatment in each specific case. Further laboratory diagnostics represent an additional supportive instrument that is used by the veterinarian at his discretion depending on the necessity. Laboratory tests of bacterial sensitivity (identification of pathogens and antibiogram) may become necessary within the framework of diagnostics. As examples demonstrate, laboratory tests of bacterial sensitivity cannot be performed in every clinical case. It appears to be desirable to further discuss the use of antibacterial veterinary pharmaceuticals in the species-specific attachments in more concrete and specific terms, taking into consideration the standards of evidence-based medicine.

Spin wave diffraction and perfect imaging of a grating.

We study the diffraction of Damon-Eshbach-type spin waves incident on a one-dimensional grating realized by microslits in a thin Permalloy film. By means of time-resolved scanning Kerr microscopy, we observe unique diffraction patterns behind the grating which exhibit replications of the spin wave field at the slits. We show that these spin wave images, with details finer than the wavelength of the incident Damon-Eshbach spin wavelength, arise from the strongly anisotropic spin wave dispersion.

Thermal conductance of ballistic point contacts.

We study the thermal conductance of ballistic point contacts. These contacts are realized as few nanometer long pillars in so-called air-gap heterostructures (AGHs). The pillar length is orders of magnitude smaller than the mean free path of the phonons up to room temperature. Because of the small dimension and the low density of the pillars, the thermal conductance of the AGHs is several orders of magnitude reduced in comparison to bulk structures. The measurement results are in quantitative agreement with a simple model that is based on the Boltzmann transport equation.

In vitro induced CD8+ regulatory T cells inhibit skin inflammation.

CD8(+) regulatory T cells appear impaired in number and/or function in some autoimmune diseases. However, the role of CD8(+) regulatory T cells in the pathogenesis of skin inflammation and psoriasis remains unknown. In this study, we set out to analyze the capability of CD8(+) regulatory T cells to inhibit skin inflammation in a murine model and to determine the frequency of CD8(+) regulatory T cells in patients with psoriasis. We demonstrate that murine fully competent CD8(+) regulatory T cells can be induced by stimulating naïve CD8(+) T cells in the presence of TGF-ß and retinoic acid (RA). Importantly, in vitro induced CD8(+) regulatory T cells significantly suppressed skin inflammation in vivo. Furthermore, we found that the frequency of regulatory CD8(+)CD25(+)Foxp3(+) T cells is decreased in peripheral blood but increased in lesional psoriatic skin of patients with psoriasis. Thus, our study suggests a previously unappreciated role of CD8(+)CD25(+)Foxp3(+) T cells in skin disorders, and induction of these cells in vitro may be an effective immunotherapy for skin inflammation.