Singular limits for the bi-laplacian operator with exponential nonlinearity in R4\R^4

Let $\Omega$ be a bounded smooth domain in $\mathbb{R}^{4}$ such that for some integer $d\geq1$ its $d$-th singular cohomology group with coefficients in some field is not zero, then problem {\Delta^{2}u-\rho^{4}k(x)e^{u}=0 & \hbox{in}\Omega, u=\Delta u=0 & \hbox{on}\partial\Omega, has a solution blowing-up, as $\rho\to0$, at $m$ points of $\Omega$, for any given number $m$.Comment: 30 pages, to appear in Ann. IHP Non Linear Analysi

Blow-up solutions for linear perturbations of the Yamabe equation

For a smooth, compact Riemannian manifold (M,g) of dimension N \geg 3, we are interested in the critical equation $$\Delta_g u+(N-2/4(N-1) S_g+\epsilon h)u=u^{N+2/N-2} in M, u>0 in M,$$ where \Delta_g is the Laplace--Beltrami operator, S_g is the Scalar curvature of (M,g), $h\in C^{0,\alpha}(M)$, and $\epsilon$ is a small parameter

Ultrasound of the plantar foot: a guide for the assessment of plantar intrinsic muscles

Plantar intrinsic muscles play a pivotal role in posture control and gait dynamics. They help maintain the longitudinal and transverse arches of the foot, and they regulate the degree and velocity of arch deformation during walking or running. Consequently, pathologies affecting the plantar intrinsic muscles (for instance, acquired and inherited neuropathies) lead to foot deformity, gait disorders, and painful syndromes. Intrinsic muscle malfunctioning is also associated with multifactorial overuse or degenerative conditions such as pes planus, hallux valgus, and plantar fasciitis. As the clinical examination of each intrinsic muscle is challenging, ultrasound is gaining a growing interest as an imaging tool to investigate the trophism of these muscular structures and the pattern of their alterations, and potentially to follow up on the effects of dedicated rehabilitation protocols. The ten plantar intrinsic muscles can be dived into three groups (medial, central and lateral) and four layers. Here, we propose a regional and landmark-based approach to the complex sonoanatomy of the plantar intrinsic muscles in order to facilitate the correct identification of each muscle from the superficial to the deepest layer. We also summarize the pathological ultrasound findings that can be encountered when scanning the plantar muscles, pointing out the patterns of alterations specific to certain conditions, such as plantar nerves mononeuropathies

High-resolution ultrasound of spigelian and groin hernias: a closer look at fascial architecture and aponeurotic passageways

From the clinical point of view, a proper diagnosis of spigelian, inguinal and femoral hernias may be relevant for orienting the patient's management, as these conditions carry a different risk of complications and require specific approaches and treatments. Imaging may play a significant role in the diagnostic work-up of patients with suspected abdominal hernias, as the identification and categorization of these conditions is often unfeasible on clinical ground. Ultrasound imaging is particularly suited for this purpose, owing to its dynamic capabilities, high accuracy, low cost and wide availability. The main limitation of this technique consists of its intrinsic operator dependency, which tends to be higher in difficult-to-scan areas such as the groin because of its intrinsic anatomic complexity. An in-depth knowledge of the anatomy of the lower abdominal wall is, therefore, an essential prerequisite to perform a targeted ultrasound examination and discriminate among different types of regional hernias. The aim of this review is to provide a detailed analysis of the fascial architecture and aponeurotic passageways of the abdominal wall through which spigelian, inguinal and femoral hernias extrude, by means of schematic drawings, ultrasound images and video clips. A reasoned landmark-based ultrasound scanning technique is described to allow a prompt and reliable identification of these pathologic conditions

A Novel Mechanism of Soluble HLA-G Mediated Immune Modulation: Downregulation of T Cell Chemokine Receptor Expression and Impairment of Chemotaxis

BACKGROUND: In recent years, many immunoregulatory functions have been ascribed to soluble HLA-G (sHLA-G). Since chemotaxis is crucial for an efficient immune response, we have investigated for the first time the effects of sHLA-G on chemokine receptor expression and function in different human T cell populations. METHODOLOGY/PRINCIPAL FINDINGS: T cell populations isolated from peripheral blood were stimulated in the presence or absence of sHLA-G. Chemokine receptors expression was evaluated by flow cytometry. sHLA-G downregulated expression of i) CCR2, CXCR3 and CXCR5 in CD4(+) T cells, ii) CXCR3 in CD8(+) T cells, iii) CXCR3 in Th1 clones iv) CXCR3 in TCR Vdelta2gamma9 T cells, and upregulated CXCR4 expression in TCR Vdelta2gamma9 T cells. sHLA-G inhibited in vitro chemotaxis of i) CD4(+) T cells towards CCL2, CCL8, CXCL10 and CXCL11, ii) CD8(+) T cells towards CXCL10 and CXCL11, iii) Th1 clones towards CXCL10, and iv) TCR Vdelta2gamma9 T cells towards CXCL10 and CXCL11. Downregulation of CXCR3 expression on CD4+ T cells by sHLA-G was partially reverted by adding a blocking antibody against ILT2/CD85j, a receptor for sHLA-G, suggesting that sHLA-G downregulated chemokine receptor expression mainly through the interaction with ILT2/CD85j. Follicular helper T cells (T(FH)) were isolated from human tonsils and stimulated as described above. sHLA-G impaired CXCR5 expression in T(FH) and chemotaxis of the latter cells towards CXCL13. Moreover, sHLA-G expression was detected in tonsils by immunohistochemistry, suggesting a role of sHLA-G in local control of T(FH) cell chemotaxis. Intracellular pathways were investigated by Western Blot analysis on total extracts from CD4+ T cells. Phosphorylation of Stat5, p70 s6k, beta-arrestin and SHP2 was modulated by sHLA-G treatment. CONCLUSIONS/SIGNIFICANCE: Our data demonstrated that sHLA-G impairs expression and functionality of different chemokine receptors in T cells. These findings delineate a novel mechanism whereby sHLA-G modulates T cell recruitment in physiological and pathological conditions

Endothelial and Smooth Muscle Cells from Abdominal Aortic Aneurysm Have Increased Oxidative Stress and Telomere Attrition

Background: Abdominal aortic aneurysm (AAA) is a complex multi-factorial disease with life-threatening complications. AAA is typically asymptomatic and its rupture is associated with high mortality rate. Both environmental and genetic risk factors are involved in AAA pathogenesis. Aim of this study was to investigate telomere length (TL) and oxidative DNA damage in paired blood lymphocytes, aortic endothelial cells (EC), vascular smooth muscle cells (VSMC), and epidermal cells from patients with AAA in comparison with matched controls. Methods: TL was assessed using a modification of quantitative (Q)-FISH in combination with immunofluorescence for CD31 or α-smooth muscle actin to detect EC and VSMC, respectively. Oxidative DNA damage was investigated by immunofluorescence staining for 7, 8-dihydro-8-oxo-2′-deoxyguanosine (8-oxo-dG). Results and Conclusions: Telomeres were found to be significantly shortened in EC, VSMC, keratinocytes and blood lymphocytes from AAA patients compared to matched controls. 8-oxo-dG immunoreactivity, indicative of oxidative DNA damage, was detected at higher levels in all of the above cell types from AAA patients compared to matched controls. Increased DNA double strand breaks were detected in AAA patients vs controls by nuclear staining for γ-H2AX histone. There was statistically significant inverse correlation between TL and accumulation of oxidative DNA damage in blood lymphocytes from AAA patients. This study shows for the first time that EC and VSMC from AAA have shortened telomeres and oxidative DNA damage. Similar findings were obtained with circulating lymphocytes and keratinocytes, indicating the systemic nature of the disease. Potential translational implications of these findings are discussed. © 2012 Cafueri et al

CD10 is a marker for cycling cells with propensity to apoptosis in childhood ALL

CD10 constitutes a favourable prognostic marker for childhood acute lymphoblastic leukaemia. Since correlations between CD10, cell cycle and apoptotic abilities were demonstrated in various cell types, we investigated whether differences existed in the cycling/apoptotic abilities of CD10-positive and CD10-negative B acute lymphoblastic leukaemia cells. Twenty-eight cases of childhood acute lymphoblastic leukaemia (mean age of 6.8 years) were subdivided into two groups according to high (17 cases, 93.2±4.5%, MRFI 211±82 CD10-positive cells) or low (11 cases, 11.5±6.2%, MRFI 10±7 CD10-negative cells) expression of CD10. CD10-positive acute lymphoblastic leukaemia cells were cycling cells with elevated c-myc levels and propensity to apoptosis, whereas CD10-negative acute lymphoblastic leukaemia cells had lower cycling capacities and c-myc levels, and were resistant to apoptosis in vitro. A close correlation between all these properties was demonstrated by the observations that the few CD10-positive cells found in the CD10-negative acute lymphoblastic leukaemia group displayed elevated c-myc and cycling capacities and were apoptosis prone. Moreover, exposure of CD10-positive acute lymphoblastic leukaemia B cells to a peptide nucleic acid anti-gene specific for the second exon of c-myc caused inhibition of c-myc expression and reduced cell cycling and apoptotic abilities as well as decreased CD10 expression