NADPH Oxidase 2-Derived Reactive Oxygen Species Promote CD8+ T Cell Effector Function.

Oxidants participate in lymphocyte activation and function. We previously demonstrated that eliminating the activity of NADPH oxidase 2 (NOX2) significantly impaired the effectiveness of autoreactive CD8+ CTLs. However, the molecular mechanisms impacting CD8+ T cell function remain unknown. In the present study, we examined the role of NOX2 in both NOD mouse and human CD8+ T cell function. Genetic ablation or chemical inhibition of NOX2 in CD8+ T cells significantly suppressed activation-induced expression of the transcription factor T-bet, the master transcription factor of the Tc1 cell lineage, and T-bet target effector genes such as IFN-γ and granzyme B. Inhibition of NOX2 in both human and mouse CD8+ T cells prevented target cell lysis. We identified that superoxide generated by NOX2 must be converted into hydrogen peroxide to transduce the redox signal in CD8+ T cells. Furthermore, we show that NOX2-generated oxidants deactivate the tumor suppressor complex leading to activation of RheB and subsequently mTOR complex 1. These results indicate that NOX2 plays a nonredundant role in TCR-mediated CD8+ T cell effector function.

ICOS ligand and IL-10 synergize to promote host-microbiota mutualism.

Genome-wide association studies have identified ICOSLG, which encodes the inducible costimulator ligand (ICOSLG or ICOSL) as a susceptibility locus for inflammatory bowel disease. ICOSL has been implicated in the enhancement of pattern recognition receptor signaling in dendritic cells, induction of IL-10 production by CD4 T cells, and the generation of high-affinity antibodies to specific antigens-all of which can potentially explain its involvement in gastrointestinal inflammation. Here, we show that murine ICOSL deficiency results in significant enrichment of IL-10-producing CD4 T cells particularly in the proximal large intestine. Transient depletion of IL-10-producing cells from adult ICOSL-deficient mice induced severe colonic inflammation that was prevented when mice were first treated with metronidazole. ICOSL-deficient mice displayed reduced IgA and IgG antibodies in the colon mucus and impaired serum antibody recognition of microbial antigens, including flagellins derived from mucus-associated bacteria of the Lachnospiraceae family. Confirming the synergy between ICOSL and IL-10, ICOSL deficiency coupled with CD4-specific deletion of the Il10 gene resulted in juvenile onset colitis that was impeded when pups were fostered by ICOSL-sufficient dams. In this setting, we found that both maternally acquired and host-derived antibodies contribute to the life anti-commensal antibody repertoire that mediates this protection in early life. Collectively, our findings reveal a partnership between ICOSL-dependent anti-commensal antibodies and IL-10 in adaptive immune regulation of the microbiota in the large intestine. Furthermore, we identify ICOSL deficiency as an effective platform for exploring the functions of anti-commensal antibodies in host-microbiota mutualism.

Impact of particle size of cereals and soyabean meal on the intestinal development of weanling pigs and growth performance after an enteric challenge with F4-positive enterotoxigenic E. coli.

The objectives were to determine the interactive effect of particle size of soyabean meal (SBM) and whole wheat, barley and wheat bran (CER) on growth performance of weanling pigs after an enterotoxigenic Escherichia coli F4 challenge (Experiment 1) and on gastrointestinal (GIT) development immediately after weaning (Experiment 2). Experiment 1 consisted of 192 pigs (24 ± 3 days of age; 7.4 ± 1.1 kg weaning bodyweight [BW]) selected for Escherichia coli (E. coli) F4 susceptibility. Pigs were given an oral E. coli inoculum at postweaning day 7, to induce an enteric health challenge. Experiment 2 consisted of 40 pigs (24 ± 3 days of age; 7.2 ± 1.0 kg weaning BW) that were killed on postweaning day 8 or 9, to determine the effects of particle size on GIT development and functionality. Four experimental diets were used in a 2 × 2 factorial design: (1) coarse CER and coarse SBM, (2) coarse CER and fine SBM (CERcSBMf), (3) fine CER and coarse SBM, or (4) fine CER and fine SBM (CERfSBMf). Results showed no interaction between SBM and CER coarseness on growth performance, GIT development and functionality. Diarrhoea incidence was higher (p < 0.05) for CERfSBMf during the 2 weeks following the E. coli challenge compared to the other diets. Daily gain and feed intake during this period were higher (p < 0.05) for pigs fed CERc compared to CERf. Empty stomach weight tended to be greater by 8% (p = 0.09) for CERc compared to CERf. Gastric protein (p = 0.05) and starch (p = 0.04) disappearances were greater for SBMf compared to SBMc. Thus, CERcSBMf resulted in the best growth performance and lowest diarrhoea incidence during the 2 weeks following the E. coli challenge, which may be explained by changes in stomach functionality but not by changes in other parts of the GIT.

Localized cytotoxic T cell-associated antigen 4 and antioxidant islet encapsulation alters macrophage signaling and induces regulatory and anergic T cells to enhance allograft survival.

The loss of functional ß-cell mass is a hallmark of type 1 diabetes. Islet transplantation represents a promising alternative approach, but immune-mediated graft destruction remains a major challenge. We sought to use islet encapsulation technologies to improve graft survival and function without systemic immunosuppression. We hypothesized islet encapsulation with nanothin coatings consisting of tannic acid (TA), an antioxidant; poly(N-vinylpyrrolidone) (PVPON), a biocompatible polymer; and cytotoxic T cell-associated antigen 4 immunoglobulin (CTLA-4-Ig), an inhibitory immune receptor, will elicit localized immunosuppression to prolong islet allograft function and suppress effector T cell responses. In the absence of systemic immunosuppression, we demonstrated (PVPON/TA/CTLA-4-Ig)-encapsulated NOD.Rag islet grafts maintain function significantly longer than control IgG-containing (PVPON/TA/IgG) and nonencapsulated controls after transplantation into diabetic C57BL/6 mice. This protection coincided with diminished proinflammatory macrophage responses mediated by signal transducer and activator of transcription 1 signaling, decreased proinflammatory T cell effector responses, and CTLA-4-Ig-specific concomitant increases in anergic CD4+ T cells and regulatory T cells. Our results provide evidence that conjugation of CTLA-4-Ig to (PVPON/TA) coatings can suppress T cell activation, enhance regulatory T cell populations, prolong islet allograft survival, and induce localized immunosuppression after transplantation.

Deletion of Tbc1d4/As160 abrogates cardiac glucose uptake and increases myocardial damage after ischemia/reperfusion.

BACKGROUND: Type 2 Diabetes mellitus (T2DM) is a major risk factor for cardiovascular disease and associated with poor outcome after myocardial infarction (MI). In T2DM, cardiac metabolic flexibility, i.e. the switch between carbohydrates and lipids as energy source, is disturbed. The RabGTPase-activating protein TBC1D4 represents a crucial regulator of insulin-stimulated glucose uptake in skeletal muscle by controlling glucose transporter GLUT4 translocation. A human loss-of-function mutation in TBC1D4 is associated with impaired glycemic control and elevated T2DM risk. The study's aim was to investigate TBC1D4 function in cardiac substrate metabolism and adaptation to MI. METHODS: Cardiac glucose metabolism of male Tbc1d4-deficient (D4KO) and wild type (WT) mice was characterized using in vivo [18F]-FDG PET imaging after glucose injection and ex vivo basal/insulin-stimulated [3H]-2-deoxyglucose uptake in left ventricular (LV) papillary muscle. Mice were subjected to cardiac ischemia/reperfusion (I/R). Heart structure and function were analyzed until 3 weeks post-MI using echocardiography, morphometric and ultrastructural analysis of heart sections, complemented by whole heart transcriptome and protein measurements. RESULTS: Tbc1d4-knockout abolished insulin-stimulated glucose uptake in ex vivo LV papillary muscle and in vivo cardiac glucose uptake after glucose injection, accompanied by a marked reduction of GLUT4. Basal cardiac glucose uptake and GLUT1 abundance were not changed compared to WT controls. D4KO mice showed mild impairments in glycemia but normal cardiac function. However, after I/R D4KO mice showed progressively increased LV endsystolic volume and substantially increased infarction area compared to WT controls. Cardiac transcriptome analysis revealed upregulation of the unfolded protein response via ATF4/eIF2α in D4KO mice at baseline. Transmission electron microscopy revealed largely increased extracellular matrix (ECM) area, in line with decreased cardiac expression of matrix metalloproteinases of D4KO mice. CONCLUSIONS: TBC1D4 is essential for insulin-stimulated cardiac glucose uptake and metabolic flexibility. Tbc1d4-deficiency results in elevated cardiac endoplasmic reticulum (ER)-stress response, increased deposition of ECM and aggravated cardiac damage following MI. Hence, impaired TBC1D4 signaling contributes to poor outcome after MI.

Diet and stomach characteristics of feral piglets (Sus scrofa): Implications for farmed piglets.

Evaluation of the diet of the pig (Sus scrofa) in natural settings may provide new views on diet optimization for growth and development of commercially raised piglets under farm conditions. A field study was conducted to gain insight in the diet and stomach characteristics of feral piglets. Forty animals (body weight: 4.6 ± 1.37 kg) were collected from the Bahía Samborombón (Buenos Aires, Argentina). Stomachs were weighed after storage in formalin and the particle size distribution of their contents was determined by wet sieving. Diet items present in their stomachs were classified and their proportional weight and relative abundance was calculated. Based on their dentition, 5, 16 and 19 piglets were approximately 1, 3-6 and 6-16 weeks of age respectively. Vegetable matter (mainly 'leaves and stems') was predominantly present in 39 animals. It represented on average 83 ± 36.4% of total stomach contents by weight. The stomachs of 12 piglets contained curd and represented on average 16 ± 35.1% by weight. Other diet items were less abundant or absent. The proportion of stomach particles retained were 24%, 13%, 22%, 13% and 28% for sieves with mesh sizes of 2000, 1000, 420, 210 and <210 µm respectively. For comparison, we used data of farmed piglets of similar age and fed a nutrient-dense, finely ground diet. Feral piglets' relative empty stomach weights increased with age (p < 0.050), whereas this was not the case for farmed piglets. Relative stomach contents weight increased significantly with age only for farmed piglets (p < 0.050). We infer from our data that feral suckling piglets consumed a variety of non-milk items, mainly consisting of vegetable material with a coarse particle size from their first week in life onwards. Their diet is associated with an enhanced stomach development compared to those of farmed piglets.

[Soft tissue necrotizing infection]. / L'image du mois. Infection nécrosante des tissus mous.

Necrotizing fasciitis and gas gangrene represent a rapidly progressive and fatal tissue infection in the absence of early multidisciplinary treatment. There are multiple risk factors, but diabetes remains the main one. The presence of crackles or extensive lesions are an indication for exploration and surgical treatment. Conservative management is associated with zero survival. Iconography, biology or bacteriology can help in the diagnosis, but the latter is only made during surgery. The associated mortality is high, despite appropriate management. We report here the case of a diabetic patient requiring insulin, having presented this pathology, the starting point of which is a traumatic wound, with an extensive acute course, contra-indicating any surgical procedure.

La fasciite nécrosante et la gangrène gazeuse représentent une infection tissulaire rapidement progressive et létale en l'absence d'un traitement multidisciplinaire précoce. Il existe de multiples facteurs de risques, mais le diabète en reste le principal. La présence de crépitants ou de lésions extensives sont une indication à l'exploration et au traitement chirurgical. Une prise en charge conservatrice est associée à une survie nulle. L'iconographie, la biologie ou la bactériologie permettent d'aider au diagnostic, mais ce dernier est uniquement posé en per-opératoire. La mortalité associée est élevée, malgré une prise en charge adaptée. Nous rapportons ici le cas d'un patient diabétique de type 2 insulino-requérant, ayant présenté cette pathologie dont le point de départ est une plaie traumatique, avec une évolution aiguë extensive, contre-indiquant tout geste chirurgical.

Scallop Theorem and Swimming at the Mesoscale.

By comparing theoretical modeling, simulations, and experiments, we show that there exists a swimming regime at low Reynolds numbers solely driven by the inertia of the swimmer itself. This is demonstrated by considering a dumbbell with an asymmetry in coasting time in its two spheres. Despite deforming in a reciprocal fashion, the dumbbell swims by generating a nonreciprocal Stokesian flow, which arises from the asymmetry in coasting times. This asymmetry acts as a second degree of freedom, which allows the scallop theorem to be fulfilled at the mesoscopic scale.

Xenotransplantation of tannic acid-encapsulated neonatal porcine islets decreases proinflammatory innate immune responses.

BACKGROUND: Islet transplantation with neonatal porcine islets (NPIs) is a promising treatment for type 1 diabetes (T1D), but immune rejection poses a major hurdle for clinical use. Innate immune-derived reactive oxygen species (ROS) synthesis can facilitate islet xenograft destruction and enhance adaptive immune responses. METHODS: To suppress ROS-mediated xenograft destruction, we utilized nanothin encapsulation materials composed of multilayers of tannic acid (TA), an antioxidant, and a neutral polymer, poly(N-vinylpyrrolidone) (PVPON). We hypothesized that (PVPON/TA)-encapsulated NPIs will maintain euglycemia and dampen proinflammatory innate immune responses following xenotransplantation. RESULTS: (PVPON/TA)-encapsulated NPIs were viable and glucose-responsive similar to non-encapsulated NPIs. Transplantation of (PVPON/TA)-encapsulated NPIs into hyperglycemic C57BL/6.Rag or NOD.Rag mice restored euglycemia, exhibited glucose tolerance, and maintained islet-specific transcription factor levels similar to non-encapsulated NPIs. Gene expression analysis of (PVPON/TA)-encapsulated grafts post-transplantation displayed reduced proinflammatory Ccl5, Cxcl10, Tnf, and Stat1 while enhancing alternatively activated macrophage Retnla, Arg1, and Stat6 mRNA accumulation compared with controls. Flow cytometry analysis demonstrated significantly reduced innate immune infiltration, MHC-II, co-stimulatory molecule, and TNF expression with concomitant increases in arginase-1+ macrophages and dendritic cells. Similar alterations in immune responses were observed following xenotransplantation into immunocompetent NOD mice. CONCLUSION: Our data suggest that (PVPON/TA) encapsulation of NPIs is an effective strategy to decrease inflammatory innate immune signals involved in NPI xenograft responses through STAT1/6 modulation without compromising islet function.

Optical quantification of intracellular mass density and cell mechanics in 3D mechanical confinement.

Biophysical properties of cells such as intracellular mass density and cell mechanics are known to be involved in a wide range of homeostatic functions and pathological alterations. An optical readout that can be used to quantify such properties is the refractive index (RI) distribution. It has been recently reported that the nucleus, initially presumed to be the organelle with the highest dry mass density (ρ) within the cell, has in fact a lower RI and ρ than its surrounding cytoplasm. These studies have either been conducted in suspended cells, or cells adhered on 2D substrates, neither of which reflects the situation in vivo where cells are surrounded by the extracellular matrix (ECM). To better approximate the 3D situation, we encapsulated cells in 3D covalently-crosslinked alginate hydrogels with varying stiffness, and imaged the 3D RI distribution of cells, using a combined optical diffraction tomography (ODT)-epifluorescence microscope. Unexpectedly, the nuclei of cells in 3D displayed a higher ρ than the cytoplasm, in contrast to 2D cultures. Using a Brillouin-epifluorescence microscope we subsequently showed that in addition to higher ρ, the nuclei also had a higher longitudinal modulus (M) and viscosity (η) compared to the cytoplasm. Furthermore, increasing the stiffness of the hydrogel resulted in higher M for both the nuclei and cytoplasm of cells in stiff 3D alginate compared to cells in compliant 3D alginate. The ability to quantify intracellular biophysical properties with non-invasive techniques will improve our understanding of biological processes such as dormancy, apoptosis, cell growth or stem cell differentiation.

LIM-domain transcription complexes interact with ring-finger ubiquitin ligases and thereby impact islet ß-cell function.

Diabetes is characterized by a loss of ß-cell mass, and a greater understanding of the transcriptional mechanisms governing ß-cell function is required for future therapies. Previously, we reported that a complex of the Islet-1 (Isl1) transcription factor and the co-regulator single-stranded DNA-binding protein 3 (SSBP3) regulates the genes necessary for ß-cell function, but few proteins are known to interact with this complex in ß-cells. To identify additional components, here we performed SSBP3 reverse-cross-linked immunoprecipitation (ReCLIP)- and MS-based experiments with mouse ß-cell extracts and compared the results with those from our previous Isl1 ReCLIP study. Our analysis identified the E3 ubiquitin ligases ring finger protein 20 (RNF20) and RNF40, factors that in nonpancreatic cells regulate transcription through imparting monoubiquitin marks on histone H2B (H2Bub1), a precursor to histone H3 lysine 4 trimethylation (H3K4me3). We hypothesized that RNF20 and RNF40 regulate similar genes as those regulated by Isl1 and SSBP3 and are important for ß-cell function. We observed that Rnf20 and Rnf40 depletion reduces ß-cell H2Bub1 marks and uncovered several target genes, including glucose transporter 2 (Glut2), MAF BZIP transcription factor A (MafA), and uncoupling protein 2 (Ucp2). Strikingly, we also observed that Isl1 and SSBP3 depletion reduces H2Bub1 and H3K4me3 marks, suggesting that they have epigenetic roles. We noted that the RNF complex is required for glucose-stimulated insulin secretion and normal mitochondrial reactive oxygen species levels. These findings indicate that RNF20 and RNF40 regulate ß-cell gene expression and insulin secretion and establish a link between Isl1 complexes and global cellular epigenetics.

Superoxide Production by NADPH Oxidase Intensifies Macrophage Antiviral Responses during Diabetogenic Coxsackievirus Infection.

Coxsackievirus B infections are suspected environmental triggers of type 1 diabetes (T1D) and macrophage antiviral responses may provide a link to virus-induced T1D. We previously demonstrated an important role for NADPH oxidase (NOX)-derived superoxide production during T1D pathogenesis, as NOX-deficient NOD mice (NOD.Ncf1m1J ) were protected against T1D due, in part, to impaired proinflammatory TLR signaling in NOD.Ncf1m1J macrophages. Therefore, we hypothesized that loss of NOX-derived superoxide would dampen diabetogenic antiviral macrophage responses and protect from virus-induced diabetes. Upon infection with a suspected diabetogenic virus, Coxsackievirus B3 (CB3), NOD.Ncf1m1J mice remained resistant to virus-induced autoimmune diabetes. A concomitant decrease in circulating inflammatory chemokines, blunted antiviral gene signature within the pancreas, and reduced proinflammatory M1 macrophage responses were observed. Importantly, exogenous superoxide addition to CB3-infected NOD.Ncf1m1J bone marrow-derived macrophages rescued the inflammatory antiviral M1 macrophage response, revealing reduction-oxidation-dependent mechanisms of signal transducer and activator of transcription 1 signaling and dsRNA viral sensors in macrophages. We report that superoxide production following CB3 infection may exacerbate pancreatic ß cell destruction in T1D by influencing proinflammatory M1 macrophage responses, and mechanistically linking oxidative stress, inflammation, and diabetogenic virus infections.

Serum miR-204 is an early biomarker of type 1 diabetes-associated pancreatic beta-cell loss.

Pancreatic beta-cell death is a major factor in the pathogenesis of type 1 diabetes (T1D), but straightforward methods to measure beta-cell loss in humans are lacking, underlining the need for novel biomarkers. Using studies in INS-1 cells, human islets, diabetic mice, and serum samples of subjects with T1D at different stages, we have identified serum miR-204 as an early biomarker of T1D-associated beta-cell loss in humans. MiR-204 is a highly enriched microRNA in human beta-cells, and we found that it is released from dying beta-cells and detectable in human serum. We further discovered that serum miR-204 was elevated in children and adults with T1D and in autoantibody-positive at-risk subjects but not in type 2 diabetes or other autoimmune diseases and was inversely correlated with remaining beta-cell function in recent-onset T1D. Thus, serum miR-204 may provide a much needed novel approach to assess early T1D-associated human beta-cell loss even before onset of overt disease.

Reduced Feed Intake, Rather than Increased Energy Losses, Explains Variation in Growth Rates of Normal-Birth-Weight Piglets.

Background: Substantial variation in growth rates exists in normal-birth-weight piglets, possibly due to differences in energy efficiency. Within this population, slow growth rates are associated with reduced insulin sensitivity. Slowly digestible starch (SDS) may improve growth efficiency in slowly growing pigs, because it reduces postprandial blood glucose. Objective: The aim of this study was to investigate maintenance energy requirements and efficiency of energy used for growth (incremental energy efficiency) of slow-growing or fast-growing piglets (SG-pigs and FG-pigs, respectively) with equal birth weight that were fed either an SDS or a rapidly digestible-starch (RDS) diet. Methods: Sixteen groups of either five 10-wk-old SG-pigs (mean ± SD: 11.3 ± 1.4 kg) or FG-pigs (15.1 ± 1.7 kg) were housed in climate respiration chambers and fed diets containing 40% RDS or SDS for 2 wk. In week 1, feed was available ad libitum. In week 2, feed supply was restricted to 65% of the observed weekly averaged feed intake [kJ · kg body weight (BW)-0.6 · d-1] in week 1. After week 2, pigs were feed deprived for 24 h, after which heat production was determined. Energy balances, apparent total tract digestibility (ATTD), and incremental energy efficiencies were calculated and analyzed using a general linear model. Results: Gross energy intake (kJ · kg BW-0.6 · d-1) was 4% greater (P = 0.047) for FG-pigs than for SG-pigs. ATTD of fat was 6%-units greater (P = 0.003) for RDS-fed than for SDS-fed pigs. Fasting heat production and incremental energy efficiencies did not differ between pig types or diets. Incremental use of metabolizable energy for fat retention was 2% units (P = 0.054) greater for RDS-fed than SDS-fed pigs. Conclusions: A lower energy intake rather than greater maintenance requirements or lower energy efficiency explains the slow growth of SG-pigs. Incremental RDS intake increased fat deposition more than SDS, whereas energy efficiency was not affected. Thus, feeding SDS instead of RDS does not improve growth efficiency but may result in slightly leaner pigs.

NADPH Oxidase-Derived Superoxide Provides a Third Signal for CD4 T Cell Effector Responses.

Originally recognized for their direct induced toxicity as a component of the innate immune response, reactive oxygen species (ROS) can profoundly modulate T cell adaptive immune responses. Efficient T cell activation requires: signal 1, consisting of an antigenic peptide-MHC complex binding with the TCR; signal 2, the interaction of costimulatory molecules on T cells and APCs; and signal 3, the generation of innate immune-derived ROS and proinflammatory cytokines. This third signal, in particular, has proven essential in generating productive and long-lasting immune responses. Our laboratory previously demonstrated profound Ag-specific hyporesponsiveness in the absence of NADPH oxidase-derived superoxide. To further examine the consequences of ROS deficiency on Ag-specific T cell responses, our laboratory generated the OT-II.Ncf1(m1J) mouse, possessing superoxide-deficient T cells recognizing the nominal Ag OVA323-339 In this study, we demonstrate that OT-II.Ncf1(m1J) CD4 T cells displayed a severe reduction in Th1 T cell responses, in addition to blunted IL-12R expression and severely attenuated proinflammatory chemokine ligands. Conversely, IFN-γ synthesis and IL-12R synthesis were rescued by the addition of exogenous superoxide via the paramagnetic superoxide donor potassium dioxide or superoxide-sufficient dendritic cells. Ultimately, these data highlight the importance of NADPH oxidase-derived ROS in providing a third signal for adaptive immune maturation by modulating the IL-12/IL-12R pathway and the novelty of the OT-II.Ncf1(m1J) mouse model to determine the role of redox-dependent signaling on effector responses. Thus, targeting ROS represents a promising therapeutic strategy in dampening Ag-specific T cell responses and T cell-mediated autoimmune diseases, such as type 1 diabetes.

Surface swimmers, harnessing the interface to self-propel.

In the study of microscopic flows, self-propulsion has been particularly topical in recent years, with the rise of miniature artificial swimmers as a new tool for flow control, low Reynolds number mixing, micromanipulation or even drug delivery. It is possible to take advantage of interfacial physics to propel these microrobots, as demonstrated by recent experiments using the proximity of an interface, or the interface itself, to generate propulsion at low Reynolds number. This paper discusses how a nearby interface can provide the symmetry breaking necessary for propulsion. An overview of recent experiments illustrates how forces at the interface can be used to generate locomotion. Surface swimmers ranging from the microscopic scale to typically the capillary length are covered. Two systems are then discussed in greater detail. The first is composed of floating ferromagnetic spheres that assemble through capillarity into swimming structures. Two previously studied configurations, triangular and collinear, are discussed and contrasted. A new interpretation for the triangular swimmer is presented. Then, the non-monotonic influence of surface tension and viscosity is evidenced in the collinear case. Finally, a new system is introduced. It is a magnetically powered, centimeter-sized piece that swims similarly to water striders.

Tinea Capitis Masquerading as Basal Cell Carcinoma.

A 52-year-old white man with alcoholic cirrhosis presented to the Mohs surgery clinic with a 1-month history of tender "bumps" located diffusely on his scalp. Two biopsies performed at an outside institution were read as "basal cell carcinoma" and "actinic keratosis." The patient was scheduled for a large excision of the scalp for presumed multiple nodules of basal cell carcinoma and desired a second opinion from our Mohs surgery clinic.

Polarization of Macrophages toward M2 Phenotype Is Favored by Reduction in iPLA2ß (Group VIA Phospholipase A2).

Macrophages are important in innate and adaptive immunity. Macrophage participation in inflammation or tissue repair is directed by various extracellular signals and mediated by multiple intracellular pathways. Activation of group VIA phospholipase A2 (iPLA2ß) causes accumulation of arachidonic acid, lysophospholipids, and eicosanoids that can promote inflammation and pathologic states. We examined the role of iPLA2ß in peritoneal macrophage immune function by comparing wild type (WT) and iPLA2ß-/- mouse macrophages. Compared with WT, iPLA2ß-/- macrophages exhibited reduced proinflammatory M1 markers when classically activated. In contrast, anti-inflammatory M2 markers were elevated under naïve conditions and induced to higher levels by alternative activation in iPLA2ß-/- macrophages compared with WT. Induction of eicosanoid (12-lipoxygenase (12-LO) and cyclooxygenase 2 (COX2))- and reactive oxygen species (NADPH oxidase 4 (NOX4))-generating enzymes by classical activation pathways was also blunted in iPLA2ß-/- macrophages compared with WT. The effects of inhibitors of iPLA2ß, COX2, or 12-LO to reduce M1 polarization were greater than those to enhance M2 polarization. Certain lipids (lysophosphatidylcholine, lysophosphatidic acid, and prostaglandin E2) recapitulated M1 phenotype in iPLA2ß-/- macrophages, but none tested promoted M2 phenotype. These findings suggest that (a) lipids generated by iPLA2ß and subsequently oxidized by cyclooxygenase and 12-LO favor macrophage inflammatory M1 polarization, and (b) the absence of iPLA2ß promotes macrophage M2 polarization. Reducing macrophage iPLA2ß activity and thereby attenuating macrophage M1 polarization might cause a shift from an inflammatory to a recovery/repair milieu.

Application of Solution-Focused Brief Therapy (SFBT) in individuals after stroke.

OBJECTIVE: To examine the effects of Solution Focused Brief Therapy (SFBT) in individuals after stroke on self-efficacy, symptoms of depression and anxiety. DESIGN: Randomized controlled trial. SETTING: Clinic of Adult Neurology of Medical University of Gdansk and M. Copernicus Pomeranian Traumatology Centre in Gdansk. SUBJECTS: A total of 62 patients, aged 54.0 ± 9.6 years. INTERVENTIONS: They were randomly assigned to one of the two groups: SFBT participating in 10 therapy sessions and control - not participating in any psychotherapy. MAIN MEASURES: Symptoms of depression and anxiety according to Hospital Anxiety and Depression Scale, Mini-Mental Adjustment to Cancer (scale originally designed for cancer patients) and Self-efficacy Scale were examined at baseline of the study and later in the same time intervals in both groups. RESULTS: The intensity of depression and anxiety complaints drops in the SFBT group (from 5.0 to 2.0 and 8.0 to 4.0 respectively; both p < .001 Friedman's ANOVA (analysis of variance)) whilst in the control group remains unchanged. In addition to the gradual reduction of destructive attitudes (from 34.5 to 17.0), the increase in the number of constructive attitudes (from 42.0 to 50.5) and increased self-efficacy (from 79.0 to 96.0) was observed after therapy but not in the control group. CONCLUSIONS: The authors suggest SFBT as a simple, beneficial and inexpensive method to manage patients after stroke.

[Euthanasia and organ donation]. / Euthanasie et don d'organes.

We report the case of a 61 year's old patient with an amyotrophic lateral sclerosis who donates his organs after being euthanised. We recall here the strict legal framework of euthanasia and organ donation in Belgium. We also highlight the absolute need to respect the ethical principles essential for the correct implementation of both procedures.

Nous rapportons le cas d'un patient de 61 ans présentant une sclérose latérale amyotrophique qui a été donneur d'organes dans les suites immédiates d'une euthanasie. Nous rappelons le cadre légal de l'euthanasie et du don d'organes en Belgique et le respect des principes éthiques indispensables au bon déroulement de l'association de ces deux procédures.