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Anaphylaxis is a potentially life-threatening, severe allergic reaction. The immediate assessment of patients having an allergic reaction and prompt administration of epinephrine, if criteria for anaphylaxis are met, promote optimal outcomes. National and international guidelines for the management of anaphylaxis, including those for management of allergic reactions at school, as well as several clinical reports from the American Academy of Pediatrics, recommend the provision of written emergency action plans to those at risk of anaphylaxis, in addition to the prescription of epinephrine autoinjectors. This clinical report provides information to help health care providers understand the role of a written, personalized allergy and anaphylaxis emergency plan to enhance the care of children at risk of allergic reactions, including anaphylaxis. This report offers a comprehensive written plan, with advice on individualizing instructions to suit specific patient circumstances. [ABSTRACT FROM AUTHOR]

This study investigated the photophysical and photobiological properties of a new amphiphilic chlorin photosensitiser, disulfonated tetraphenylchlorin (TPCS2a), for photochemical internalisation (PCI). The absorption and fluorescence spectra of TPCS2a were examined in a range of solvents together with fluorescence lifetime measurements. The fluorescence lifetime of TPCS2a was found to be 8.5 ns in methanol, whereas non-exponential decays were observed in distilled water due to sensitiser dimerisation. The singlet oxygen quantum yield of TPCS2a was determined as 0.62 in deuterated methanol by direct observation of singlet oxygen phosphorescence. In a human oral squamous carcinoma (HN5) cell line, intracellular co-localisation of TPCS2a and Alexa488-labelled saporin, a macromolecular toxin, was observed corresponding predominantly to a lysosomal distribution. Intracellular fluorescence redistribution of TPCS2a and Alexa488-saporin was observed after 405 nm irradiation. Using two-photon confocal microscopy at 840 nm, and fluorescence lifetime imaging (FLIM), the lifetime was measured as 6 ns in HN5 cells. PCI using TPCS2a was shown to be very effective, and a synergistic increase in saporin toxicity was achieved in HN5 cells where viability was significantly reduced after light exposure compared to saporin (25 nM) treatment alone. The results demonstrate the favourable photophysical and photobiological properties of TPCS2a for PCI, which induces the relocalisation of a macromolecular anti-cancer toxin inside cells and significantly enhances cell death. [ABSTRACT FROM AUTHOR]

The article provides a summary of the Synopsis Book by the American Academy of Pediatrics on advances and key observations that will impact the care of children with allergic and immunologic diseases from 2016 to 2017. Topics discussed include an increase in the prevalence of allergic diseases, studies on anaphylaxis and the need for education on preparedness and management and studies on immunotherapy for food allergy.

The article discusses research which evaluates the beneficial effects of routine immunotherapy as an early intervention in patients with childhood-onset atopic asthma. It references a study by H. Nagaya and colleagues in a 2006 issue of the "International Archives of Allergy and Immunology." The beneficial effects of immunotherapy on forced expiratory volume in 1 second (FEV1) were analyzed retrospectively in 43 unselected patients. Results showed that there was a significant inverse correlation between the duration of asthma symptoms before immunotherapy and the changes in FEV1 before and after immunotherapy. It is recommended that immunotherapy should be started as early as possible at the youngest age.

The αvβ6 integrin receptor has been shown to be overexpressed on many types of cancer cells, resulting in a more pro-invasive and aggressive phenotype, this makes it an attractive target for selective drug delivery. In tumours that over-express the αvβ6 receptor, cellular uptake of liposomes can be enhanced using ligand-targeted liposomes. It has previously been shown in both in vitro and in vivo studies that liposomal alendronate (L-ALD) can sensitise cancer cells to destruction by Vγ9Vδ2 T cells. It is hypothesised that by using the αvβ6-specific peptide A20FMDV2 as a targeting moiety for L-ALD, the therapeutic efficacy of this therapy can be increased in αvβ6 positive tumours. Targeted liposomes (t-L) were formulated and the targeting efficacy of targeted liposomes (t-L) was assessed by cell uptake and cytotoxicity studies in the αvβ6 positive cells line A375Pβ6. Bio-distribution of both L and t-L were carried out in αvβ6 positive (A375Pβ6 and PANC0403) and αvβ6 negative (A375Ppuro and PANC-1) subcutaneous tumour mouse models. Immuno-compromised mice bearing A375Pβ6 experimental metastatic lung tumours were treated with L-ALD or t-L-ALD as monotherapies or in combination with ex vivo -expanded Vγ9Vδ2 T cells. In vitro , αvβ6-dependant uptake of t-L was observed, with t-L-ALD being more effective than L-ALD at sensitising A375Pβ6 to γδ T cells. Interestingly, t-L-ALD led to slightly higher but not significant reduction in tumour growth compared to L-ALD, when used as monotherapy in vivo . Moreover, both L-ALD and t-L-ALD led to significant reductions in tumour growth when used in combination with γδ T cells in vivo but t-L-ALD offered no added advantage compared to L-ALD. [ABSTRACT FROM AUTHOR]

Nitrogen-containing bisphosphonates (N-BP), including zoledronic acid (ZOL) and alendronate (ALD), have been proposed as sensitisers in γδ T cell immunotherapy in pre-clinical and clinical studies. Therapeutic efficacy of N-BPs is hampered by their rapid renal excretion and high affinity for bone. Liposomal formulations of N-BP have been proposed to improve accumulation in solid tumours. Liposomal ALD (L-ALD) has been suggested as a suitable alternative to liposomal ZOL (L-ZOL), due to unexpected mice death experienced in pre-clinical studies with the latter. Only one study so far has proven the therapeutic efficacy of L-ALD, in combination with γδ T cell immunotherapy, after intraperitoneal administration of γδ T cell resulting in delayed growth of ovarian cancer in mice. This study aims to assess the in vitro efficacy of L-ALD, in combination with γδ T cell immunotherapy, in a range of cancerous cell lines, using L-ZOL as a comparator. The therapeutic efficacy was tested in a pseudo-metastatic lung mouse model, following intravenous injection of γδ T cell, L-ALD or the combination. In vivo biocompatibility and organ biodistribution studies of L-N-BPs were undertaken simultaneously. Higher concentrations of L-ALD (40–60 μM) than L-ZOL (3–10 μM) were required to produce a comparative reduction in cell viability in vitro, when used in combination with γδ T cells. Significant inhibition of tumour growth was observed after treatment with both L-ALD and γδ T cells in pseudo-metastatic lung melanoma tumour-bearing mice after tail vein injection of both treatments, suggesting that therapeutically relevant concentrations of L-ALD and γδ T cell could be achieved in the tumour sites, resulting in significant delay in tumour growth. [ABSTRACT FROM AUTHOR]

Objective: To investigate the outcomes of two surgical interventions for Peyronie's disease (PD) with hourglass deformity: partial excision and grafting (PEG) or inflatable penile prosthesis (IPP) implantation.Materials and Methods: Retrospective data were collected from two centers: Technical University of Munich (PEG) and Tulane University Medical Center (IPP). Collected variables included patient demographics, sexual function, penile vascular measurements, and treatment outcomes.Results: A total of 50 PD patients with hourglass deformity (26 PEG [group 1] and 24 IPP [group 2]) were included in this study. Patients in group 1 had higher mean preoperative Sexual Health Inventory for Men scores (22.2 vs 10.3, P < 0001), required less erectile dysfunction treatment (35% vs 79%, P = .005), and had more nonvascular etiology (77% vs 21%, P < .0001). There were no intraoperative complications, 2 patients in group 1 had postoperative glans hypoesthesia, and 1 patient in group 2 required surgical revision. All patients in both groups had significant ≥20% improvements in penile curvature with mean changes of 68.1 degrees (12.7) in group 1 and 49.6 degrees (13.5) in group 2, P < .0001. Resolution of hourglass deformity was achieved in 85% of patients in group 1 and 100% of patients in group 2, P = .045. The mean postoperative change in Sexual Health Inventory for Men score was -0.3 (1.3) in group 1 and 16.7 (4.7) in group 2, P < .0001.Conclusion: Both options provide excellent outcomes for well-selected patients with PD and an hourglass deformity. PEG can be offered to patients with good erectile function, whereas the IPP remains the preferred option for patients with poor erections. [ABSTRACT FROM AUTHOR]

With a dismal survival rate, pancreatic cancer (PC) remains one of the most aggressive and devastating malignancies, predominantly due to the absence of a valid biomarker for diagnosis and limited therapeutic options for advanced diseases. Exosomes (Exo) as cell-derived vesicles, are widely used as natural nanocarriers for drug delivery. P21-activated kinase 4 (PAK4) is oncogenic when overexpressed, promoting cell survival, migration and anchorage-independent growth. Herein we validated PAK4 as a therapeutic target in an in vivo PC tumour mouse model using Exo-mediated RNAi following intra-tumoural administration. PC derived Exo were firstly isolated by ultracentrifugation on sucrose cushion and characterised for their surface marker expression, size, number, purity and morphology. SiRNA was encapsulated into Exo via electroporation and dual uptake of Exo and siRNA was investigated by flow cytometry and confocal microscopy. In vitro siPAK4 silencing in PC cells following uptake was assessed by flow cytometry, western blotting, and in vitro scratch assay. In vivo efficacy (tumour growth delay and mouse survival) of siPAK4 was evaluated in PC bearing NSG mouse model. Ex vivo tumours were examined using Haematoxylin and eosin (H&E) staining and immunohistochemistry. Results showed high quality PC-derived PANC-1 Exo were obtained. SiRNA was incorporated in Exo with 16.5% encapsulation efficiency. In vitro imaging confirmed Exo and siRNA co-localisation in cells. PAK4 knockdown was successful with 30 nM Exo-siPAK4 at 24 h post incubation in vitro. Intra-tumoural administration of Exo-siPAK4 (0.03 mg/kg siPAK4 and 6.1 × 1011 Exo, each dose, two doses) reduced PC tumour growth in vivo and enhanced mice survival (p < 0.001), with minimal toxicity observed compared to polyethylenimine (PEI) used as a commercial transfection reagent. H&E staining of tumours showed significant tissue apoptosis in siPAK4 treated groups. PAK4 knockdown prolongs survival of PC-bearing mice suggesting its potential as a new therapeutic target for PC. PANC-1 Exo demonstrated comparable efficacy but safer profile than PEI as in vivo RNAi transfection reagent. Image 1 [ABSTRACT FROM AUTHOR]

The aim of this in vitro study is to prepare and characterize drug free and pentamidine loaded chitosan glutamate coated niosomes for intranasal drug delivery to reach the brain through intranasal delivery. Mucoadhesive properties and stability testing in various environments were evaluated to examine the potential of these formulations to be effective drug delivery vehicles for intranasal delivery to the brain. Samples were prepared using thin film hydration method. Changes in size and ζ-potential of coated and uncoated niosomes with and without loading of pentamidine in various conditions were assessed by dynamic light scattering (DLS), while size and morphology were also studied by atomic force microscopy (AFM). Bilayer properties and mucoadhesive behavior were investigated by fluorescence studies and DLS analyses, respectively. Changes in vesicle size and ζ-potential values were shown after addition of chitosan glutamate to niosomes, and when in contact with mucin solution. In particular, interactions with mucin were observed in both drug free and pentamidine loaded niosomes regardless of the presence of the coating. The characteristics of the proposed systems, such as pentamidine entrapment and mucin interaction, show promising results to deliver pentamidine or other possible drugs to the brain via nasal administration. [ABSTRACT FROM AUTHOR]