Interleukin-12 message in a bottle

IL12 is a very potent cancer immunotherapy agent, but is difficult to harness safely if given systemically. Local gene transfer aims to confine the effects of IL12 to malignant tissues, thus avoiding toxicity. Lipid-nanoparticle mRNA achieves IL12 expression and efficacy in mouse models, opening the way to an ongoing trial

Procedural Impact of a Kissing-Balloon Predilation (Pre-Kissing) Technique in Patients With Complex Bifurcations Undergoing Drug-Eluting Stenting

Aim: To assess the impact of lesion predilation with kissing inflation using under-sized balloons (pre-kissing [PK]) on the procedural outcome of percutaneous intervention (PCI) on coronary bifurcation lesions (CBLs). Methods: Patients who underwent PCI with second-generation drug-eluting stenting on a complex CBL (Medina 1,1,1 or 1,0,1 or 0,1,1) were selected. The study population was divided according to the lesion preparation into the PK group and the control group. To adjust for higher anatomic complexity of PK patients, a 2:1 propensity-matched (PM)-control group was selected. The PCI procedural details were assessed to evaluate occurrence of "side-branch trouble" (primary procedural endpoint) after main-vessel (MV) stenting. Angiographic characteristics, including side-branch TIMI flow during PCI, were also systematically evaluated. Results: A total of 538 patients were identified, with 66 patients in the PK group, 472 patients in the control group, and 126 patients in the PM-control group. Side-branch trouble was less common in side-branch PK patients vs the PM-control patients (7.5% vs 18.0%, respectively; P=.03). In multivariable analysis, the absence of PK independently predicted side-branch trouble. Among selected patients with a long side-branch lesion (122 patients), the PK technique improved post-MV stenting side-branch TIMI flow. Conclusions: Use of PK with under-sized balloons may facilitate side-branch management after MV stenting in patients with complex CBL undergoing provisional stenting

Human and animal integrated influenza surveillance: a novel sampling approach for an additional transmission way in the aquatic bird reservoir.

Background: infectious low pathogenic avian influenza viruses (LPAIVs) have been recently detected on feathers of wild ducks. Laboratory trial results suggested that the preen oil gland secretion, covering waterbirds\u2019 feathers, may attract and concentrate virus particles from AIV-contaminated waters to birds\u2019 bodies. We evaluated whether ducks can become infected by the ingestion of preen oil-associated viral particles, experimentally smeared on their plumage. In addition, we compared virologic and serologic results obtained from mallards whose feathers were experimentally infected, with those from wild mallards naturally carrying AIVs on feathers. Methods: we experimentally coated 7 mallards (Anas plathyrynchos) using preen oil mixed with a LPAIV (H10N7 subtype), and housed them for 45 days with a control, uncoated duck. Cloacal, oropharyngeal and feather swabs were collected from all birds and examined for AIV molecular detection and isolation. Blood samples were also taken to detect influenza specific antibodies. In addition, sera from 10 wild mallards, carrying on feathers infectious LPAIV H10N7, were examined. Results: virologic and serologic results indicated that through self- and allopreening all the birds experimentally coated with the preen oil/AIV mix and the control duck ingested viruses covering feathers and became infected. Virus isolation from feathers was up to 32 days post-coating treatment. One out of 8 wild mallards showing antibodies against type A influenza virus was seropositive for H10 subtype too. Conclusions: our experimental and field results show evidences suggesting that uninfected birds carrying viruses on their feathers, including immune ones, might play an active role in spreading AIV infection in nature. For this reason, routine AIV surveillance programs, aimed at detecting intestinal and/or respiratory viruses, should include the collection of samples, such as feather swabs, enabling the detection of viruses sticky to preened birds\u2019 bodies

Adiabatic description of nonspherical quantum dot models

Within the effective mass approximation an adiabatic description of spheroidal and dumbbell quantum dot models in the regime of strong dimensional quantization is presented using the expansion of the wave function in appropriate sets of single-parameter basis functions. The comparison is given and the peculiarities are considered for spectral and optical characteristics of the models with axially symmetric confining potentials depending on their geometric size making use of the total sets of exact and adiabatic quantum numbers in appropriate analytic approximations

Molecular analysis of avian H7 influenza viruses circulating in Eurasia in 1999-2005: detection of multiple reassortant virus genotypes.

Avian influenza infections by high and low pathogenicity H7 influenza viruses have caused several outbreaks in European poultry in recent years, also resulting in human infections. Although in some cases the source of H7 strains from domestic poultry was shown to be the viruses circulating in the wild bird reservoir, a thorough characterization of the entire genome of H7 viruses from both wild and domestic Eurasian birds, and their evolutionary relationships, has not been conducted. In our study, we have analysed low pathogenicity H7 influenza strains isolated from wild and domestic ducks in Italy and southern China and compared them with those from reared terrestrial poultry such as chicken and turkey. Phylogenetic analysis demonstrated that the H7 haemagglutinin genes were all closely related to each other, whereas the remaining genes could be divided into two or more phylogenetic groups. Almost each year different H7 reassortant viruses were identified and in at least two different years more than one H7 genotype co-circulated. A recent precursor in wild waterfowl was identified for most of the gene segments of terrestrial poultry viruses. Our data suggest that reassortment allows avian influenza viruses, in their natural reservoir, to increase their genetic diversity. In turn this might help avian influenza viruses colonize a wider range of hosts, including domestic poultry

Clinical-genetic features and peculiar muscle histopathology in infantile DNM1L-related mitochondrial epileptic encephalopathy

Mitochondria are highly dynamic organelles, undergoing continuous fission and fusion. The DNM1L gene encodes for the DRP1 protein, an evolutionary conserved member of the dynamin family, responsible for fission of mitochondria, and having a role in the division of peroxisomes, as well. DRP1 impairment is implicated in several neurological disorders and associated with either de novo dominant or compound heterozygous mutations. In five patients presenting with severe epileptic encephalopathy we identified 5 de novo dominant DNM1L variants, the pathogenicity of which was validated in a yeast model. Fluorescence microscopy revealed abnormally elongated mitochondria and aberrant peroxisomes in mutant fibroblasts, indicating impaired fission of these organelles. Moreover, a very peculiar finding in our cohort of patients was the presence, in muscle biopsy, of core like areas with oxidative enzyme alterations, suggesting an abnormal distribution of mitochondria in the muscle tissue