Enstrophy from symmetry

We study symmetry principles associated with the approximately conserved enstrophy current, responsible for the inverse energy cascade in non relativistic 2+1 dimensional turbulence. We do so by identifying the accidental symmetry associated with enstrophy current conservation in a recently realized effective action principle for hydrodynamics. Our analysis deals with both relativistic and non relativistic effective actions and their associated symmetries

Testing the membrane paradigm with holography

One version of the membrane paradigm states that as far as outside observers are concerned, black holes can be replaced by a dissipative membrane with simple physical properties located at the stretched horizon. We demonstrate that such a membrane paradigm is incomplete in several aspects. We argue that it generically fails to capture the massive quasinormal modes, unless we replace the stretched horizon by the exact event horizon, and illustrate this with a scalar field in a BTZ black hole background. We also consider as a concrete example linearized metric perturbations of a five-dimensional AdS-Schwarzschild black brane and show that a spurious excitation appears in the long-wavelength response that is only removed from the spectrum when the membrane paradigm is replaced by ingoing boundary conditions at the event horizon. We interpret this excitation in terms of an additional Goldstone boson that appears due to symmetry breaking by the classical solution ending on the stretched horizon rather than the event horizon.Comment: 5 pages, 1 figure; v2: improved presentation, typos fixed, figure fixed, conclusions unchanged; v3: further improvements in the presentation, conclusions unchanged; v4: shortened, published versio

Parry-Romberg syndrome: A case with a possible association with lyme disease

Parry-Romberg syndrome is an acquired slowly progressive disease characterized by an atrophy mostly involving half of the face. The pathogenesis of this disfiguring condition is still controversial. The relationship between Parry-Romberg syndrome and Lyme disease needs to be considered in depth. A 16-year-old woman from Albania presented with linear depressions of the right side of the face, clinically compatible with Parry-Romberg syndrome. She had a positive history of Lyme disease. Borrelia infection was confirmed by the positivity of PCR and the presence of IgM antibodies. The patient received intravenous penicillin and metronidazole for 14 days. After treatment and during a 2-year follow-up, the clinical disease progression was halted and the serological and microbiological tests for Borrelia burgdorferi sensu lato were negative. We cannot exclude a coincidence, however, of the bacteriological and serological evidence. Moreover, the interruption of the disease progression after the antibiotic therapy is difficult to ignore without claiming that this association is at least suggestive

Meningitis complicated by subdural empyema and deafness caused by pneumoccoccal serotype 7F in a 17-month-old child: a case report

Despite the availability of effective antibacterial agents and vac- cines, pneumococcal meningitis and sepsis are still associated with high mortality rates and a high risk of neurological sequelae. We describe the case of a 17-month-old boy vaccinated with heptavalent pneumococcal conjugate vaccine (PCV7) who developed bacterial meningitis complicated by subdural empyema and deafness caused by Streptococcus pneumoniae serotype 7F. The 7F strain is not con- tained in PCV7 (the only vaccine on the market at the time of the onset of meningitis) but is included in the new pediatric 13-valent PCV, which may therefore prevent cases such as this in the future. The full article is free available on www.jpmh.or

Evaluation of intracellular signalling pathways in response to insulin-like growth factor I in apoptotic-resistant activated human hepatic stellate cells

BACKGROUND: Human hepatic stellate cells have been shown to be resistant to apoptotic stimuli. This is likely dependent on the activation of anti-apoptotic pathways upon transition of these cells to myofibroblast-like cells. In particular, previous studies have demonstrated an increased expression of the anti-apoptotic protein Bcl-2 and a decreased expression of the pro-apoptotic protein Bax during the transition of the hepatic stellate cell phenotype from quiescent to myofibroblast-like cells. However, the role and expression of other key anti-apoptotic and survival pathways elicited by polypeptide growth factors involved in the chronic wound healing process remain to be elucidated. In particular, insulin growth factor-I promotes chemotactic and mitogenic effects in activated human hepatic stellate cells and these effects are mediated by the activation of PI 3-K. The role of insulin growth factor-I as a survival factor in human hepatic stellate cells needs to be substantiated. The aim of this study was to evaluate the involvement of other key anti-apoptotic pathways such as PI-3K/Akt/p-Bad in response to insulin growth factor-I. RESULTS: Insulin growth factor-I induced activation of Akt followed by Bad phosphorylation after 15 minutes of incubation. These effects were PI-3k dependent since selective inhibitors of this molecule, wortmannin and LY294002, inhibited both Akt and Bad phosphorylation. The effect of insulin growth factor-I on the activation of two downstream targets of Akt activation, that is, GSK3 and FHKR, both implicated in the promotion of cell survival was also investigated. Both targets became phosphorylated after 15 minutes of incubation, and these effects were also PI-3K-dependent. Despite the activation of this survival pathway insulin growth factor-I did not have a remarkable biological effect, probably because other insulin growth factor-I-independent survival pathways were already maximally activated in the process of hepatic stellate cell activation. However, after incubation of the cells with a strong apoptotic stimuli such as Fas ligand+cycloheximide, a small percentage of hepatic stellate cells underwent programmed cell death that was partially rescued by insulin growth factor-I. CONCLUSION: In addition to Bcl-2, several other anti-apoptotic pathways are responsible for human hepatic stellate cell resistance to apoptosis. These features are relevant for the progression and limited reversibility of liver fibrosis in humans

A young infant with transient severe hypertriglyceridemia temporarily associated with meropenem administration : A case report and review of the literature

Background: Slight changes in the lipid profile can be observed over the acute phase of infectious diseases. Moreover, some antiinfective drugs can modify serum lipid concentrations, although antibiotics do not seem to have a relevant, direct, or acute effect on the lipid profile. Methods:A 75-day-old breastfed Caucasian female, born at term after a regular pregnancy, was hospitalized for osteomyelitis. She was immediately treated with intravenous meropenem and vancomycin. Therapy was effective, but after 22 days of treatment, her blood was found to be viscous with a purple shade. Results: A fasting blood sample showed serum triglycerides of 966mg/dL, total cholesterol of 258mg/dL, and high-density lipoprotein cholesterol of 15mg/dL. Secondary causes of hyperlipidemia and primary hereditary disorders were ruled out. Thereafter, the possibility that antibiotics may have had a role in the hypertriglyceridemia was considered, and meropenem was discontinued. After 72 hours of meropenem discontinuation, a sharp modification of lipid variables was observed, and further testing showed a complete normalization of the lipid profile. Conclusion: In this child with osteomyelitis, the increase in serum triglycerides appeared suddenly after 3 weeks of meropenem treatment and resolved quickly after meropenem discontinuation, thus highlighting the possible association between meropenem and lipid profile alterations. Monitoring the lipid profile should be considered in cases of long-term treatment with meropenem, and further studies on meropenem safety should include evaluation of the lipid profile

On the average box dimensions of graphs of typical continuous functions

Let X be a bounded subset of Rd and write Cu(X) for the set of uniformly continuous functions on X equipped with the uniform norm. The lower and upper box dimensions, denoted by dim̲B(graph(f)) and dim ¯ B(graph (f)) , of the graph graph (f) of a function f∈ Cu(X) are defined by dim̲B(graph(f))=limδ↘0inflogNδ(graph(f))-logδ,dim¯B(graph(f))=limδ↘0suplogNδ(graph(f))-logδ,where Nδ(graph (f)) denotes the number of δ-mesh cubes that intersect graph (f). Hyde et al. have recently proved that the box counting function(∗)logNδ(graph(f))-logδof the graph of a typical function f∈ Cu(X) diverges in the worst possible way as δ↘ 0. More precisely, Hyde et al. showed that for a typical function f∈ Cu(X) , the lower box dimension of the graph of f is as small as possible and if X has only finitely many isolated points, then the upper box dimension of the graph of f is as big as possible. In this paper we will prove that the box counting function (*) of the graph of a typical function f∈ Cu(X) is spectacularly more irregular than suggested by the result due to Hyde et al. Namely, we show the following surprising result: not only is the box counting function in (*) divergent as δ↘ 0 , but it is so irregular that it remains spectacularly divergent as δ↘ 0 even after being “averaged" or “smoothened out" using exceptionally powerful averaging methods including all higher order Hölder and Cesàro averages and all higher order Riesz–Hardy logarithmic averages. For example, if the box dimension of X exists, then we show that for a typical function f∈ Cu(X) , all the higher order lower Hölder and Cesàro averages of the box counting function (*) are as small as possible, namely, equal to the box dimension of X, and if, in addition, X has only finitely many isolated points, then all the higher order upper Hölder and Cesàro averages of the box counting function (*) are as big as possible, namely, equal to the box dimension of X plus 1.PostprintPeer reviewe

Characterisation and induction of tissue-resident gamma delta T-cells to target hepatocellular carcinoma

Immunotherapy is now the standard of care for advanced hepatocellular carcinoma (HCC), yet many patients fail to respond. A major unmet goal is the boosting of T-cells with both strong HCC reactivity and the protective advantages of tissue-resident memory T-cells (TRM). Here, we show that higher intratumoural frequencies of γδ T-cells, which have potential for HLA-unrestricted tumour reactivity, associate with enhanced HCC patient survival. We demonstrate that γδ T-cells exhibit bona fide tissue-residency in human liver and HCC, with γδTRM showing no egress from hepatic vasculature, persistence for >10 years and superior anti-tumour cytokine production. The Vγ9Vδ2 T-cell subset is selectively depleted in HCC but can efficiently target HCC cell lines sensitised to accumulate isopentenyl-pyrophosphate by the aminobisphosphonate Zoledronic acid. Aminobisphosphonate-based expansion of peripheral Vγ9Vδ2 T-cells recapitulates a TRM phenotype and boosts cytotoxic potential. Thus, our data suggest more universally effective HCC immunotherapy may be achieved by combining aminobisphosphonates to induce Vγ9Vδ2TRM capable of replenishing the depleted pool, with additional intratumoural delivery to sensitise HCC to Vγ9Vδ2TRM-based targeting

A blocking monoclonal antibody to CCL24 alleviates liver fibrosis and inflammation in experimental models of liver damage

Background & Aims: C-C motif chemokine ligand 24 (CCL24) is a chemokine that regulates inflammatory and fibrotic activities through its receptor, C-C motif chemokine receptor (CCR3). The aim of the study was to evaluate the involvement of the CCL24-CCR3 axis in liver fibrosis and inflammation and to assess the potential of its blockade, by a monoclonal anti-CCL24 antibody, as a therapeutic strategy for non-alcoholic steatohepatitis (NASH) and liver fibrosis. Methods: Expression of CCL24 and CCR3 was evaluated in liver biopsies and blood samples. CCL24 involvement in NAFLD/NASH pathogenesis was assessed in Ccl24 knockout mouse using the methionine-choline deficient (MCD) diet experimental model. Antifibrotic and anti-inflammatory effects of CM-101 were tested in the MCD and STAM mouse models and in the thioacetamide (TAA) model in rats. Liver enzymes, liver morphology, histology and collagen deposition, as well as fibrosis- and inflammation-related protein expression were assessed. Activation of hepatic stellate cells (HSCs) was evaluated in the human LX2 cell line. Results: Patients with NASH and advanced NAFLD exhibited significant expression of both CCL24 and CCR3 in liver and blood samples. In the experimental MCD-diet model, Ccl24 knockout mice showed an attenuated liver damage response compared to wild-type mice, exhibiting reduced histological NAFLD activity scores and fibrosis, as well as lower levels of liver enzymes. Blocking CCL24 using CM-101 robustly reduced liver damage in 3 experimental animal models (MCD, STAM and TAA), as demonstrated by attenuation of liver fibrosis and NAFLD activity score. Furthermore, blocking CCL24 by CM-101 significantly inhibited CCL24-induced HSC motility, α-SMA expression and pro-collagen I secretion. Conclusion: Our results reveal that blocking CCL24 significantly attenuates liver fibrosis and inflammation and may have a potential therapeutic effect in patients with NASH and/or liver fibrosis. Lay summary: CCL24 is a chemokine that regulates inflammation and fibrosis. It was found to be significantly expressed in patients with non-alcoholic steatohepatitis, in whom it regulates profibrotic processes in the liver. Herein, we show that blockade of CCL24 using a monoclonal antibody robustly attenuated liver fibrosis and inflammation in animal models, thus suggesting a potential therapeutic role for an anti-CCL24 agent