Hepatitis B vaccination coverage among Iranian children aged 15-26 months in 2006

This study in 2006 estimated the hepatitis B virus (HBV) vaccination coverage in the Islamic Republic of Iran at the national and district levels in urban, rural and remote populations of 41 university health service areas. Of 21 905 children recruited to the study, vaccination coverage based on vaccination card records was 100% in 14, 15 and 10 of the 41 university areas for the 1st, 2nd and 3rd doses of HBV respectively. National levels of HBV1, HBV2 and HBV3 coverage were 98.9%, 98.8% and 98.4% respectively. The lowest HBV vaccination coverage rate was 90.7% (in a remote district). HBV vaccination coverage was at an acceptable level in Iranian children

Spectroscopic evaluation of QDs encapsulated with a novel biocompatible polymer for cancer diagnosis

Quantum dots (QDs) are new class of fluorescent inorganic nanocrystals which have been used for in vitro and in vivo imaging. Their unique optical properties such as broad excitation spectra, narrow emission spectrum and resistance to photobleaching make them ideal for biological labeling. Sentinel lymph node biopsy is a means of ultra-staging cancer metastasis and is now the standard of care in breast cancer surgery. Localisation of sentinel nodes is also important in the treatment of head and neck cancer. Current tracers for SLN biopsy include the blue dye have various limitations that could be overcome by quantum dots that emit in near infrared range (>700 nm). To safely deliver QDs they must be encapsulated in a biocompatible coating. In this study we encapsulate CdTe QDs with new nanocomposite material based on a silsesquioxane modified poly (carbonate-urea) urethane polymer, and evaluated their spectroscopic properties

Disparate Vulnerability to Membership Inference Attacks

A membership inference attack (MIA) against a machine-learning model enables an attacker to determine whether a given data record was part of the model's training data or not. In this paper, we provide an in-depth study of the phenomenon of disparate vulnerability against MIAs: unequal success rate of MIAs against different population subgroups. We first establish necessary and sufficient conditions for MIAs to be prevented, both on average and for population subgroups, using a notion of distributional generalization. Second, we derive connections of disparate vulnerability to algorithmic fairness and to differential privacy. We show that fairness can only prevent disparate vulnerability against limited classes of adversaries. Differential privacy bounds disparate vulnerability but can significantly reduce the accuracy of the model. We show that estimating disparate vulnerability to MIAs by naïvely applying existing attacks can lead to overestimation. We then establish which attacks are suitable for estimating disparate vulnerability, and provide a statistical framework for doing so reliably. We conduct experiments on synthetic and real-world data finding statistically significant evidence of disparate vulnerability in realistic settings

Photodynamic therapy in 3D cancer models and the utilisation of nanodelivery systems

Photodynamic therapy (PDT) is the subject of considerable research in experimental cancer models mainly for the treatment of solid cancerous tumours. Recent studies on the use of nanoparticles as photosensitiser carriers have demonstrated improved PDT efficacy in experimental cancer therapy. Experiments typically employ conventional monolayer cell culture but there is increasing interest in testing PDT using three dimensional (3D) cancer models. 3D cancer models can better mimic in vivo models than 2D cultures by for example enabling cancer cell interactions with a surrounding extracellular matrix which should enable the treatment to be optimised prior to in vivo studies. The aim of this review is to discuss recent research using PDT in different types of 3D cancer models, from spheroids to nano-fibrous scaffolds, using a range of photosensitisers on their own or incorporated in nanoparticles and nanodelivery systems

Therapeutic enhancement of a cytotoxic agent using Photochemical internalisation in 3D compressed collagen constructs of ovarian cancer

Photochemical internalisation (PCI) is a method for enhancing delivery of drugs to their intracellular target sites of action. In this study we investigated the efficacy of PCI using a porphyrin photosensitiser and a cytotoxic agent on spheroid and non-spheroid compressed collagen 3D constructs of ovarian cancer versus conventional 2D culture. The therapeutic responses of two human carcinoma cell lines (SKOV3 and HEY) were compared using a range of assays including optical imaging. The treatment was shown to be effective in non-spheroid constructs of both cell lines causing a significant and synergistic reduction in cell viability measured at 48 or 96 hours post-illumination. In the larger spheroid constructs, PCI was still effective but required higher saporin and photosensitiser doses. Moreover, in contrast to the 2D and non-spheroid experiments, where comparable efficacy was found for the two cell lines, HEY spheroid constructs were found to be more susceptible to PCI and a lower dose of saporin could be used. PCI treatment was observed to induce death principally by apoptosis in the 3D constructs compared to the mostly necrotic cell death caused by PDT. At low oxygen levels (1%) both PDT and PCI were significantly less effective in the constructs

Endolysosomal targeting of a clinical chlorin photosensitiser for light-triggered delivery of nano-sized medicines

A major problem with many promising nano-sized biotherapeutics including macromolecules is that owing to their size they are subject to cellular uptake via endocytosis, and become entrapped and then degraded within endolysosomes, which can significantly impair their therapeutic efficacy. Photochemical internalisation (PCI) is a technique for inducing cytosolic release of the entrapped agents that harnesses sub-lethal photodynamic therapy (PDT) using a photosensitiser that localises in endolysosomal membranes. Using light to trigger reactive oxygen species-mediated rupture of the photosensitised endolysosomal membranes, the spatio-temporal selectivity of PCI then enables cytosolic release of the agents at the selected time after administration so that they can reach their intracellular targets. However, conventional photosensitisers used clinically for PDT are ineffective for photochemical internalisation owing to their sub-optimal intracellular localisation. In this work we demonstrate that such a photosensitiser, chlorin e6, can be repurposed for PCI by conjugating the chlorin to a cell penetrating peptide, using bioorthogonal ligation chemistry. The peptide conjugation enables targeting of endosomal membranes so that light-triggered cytosolic release of an entrapped nano-sized cytotoxin can be achieved with consequent improvement in cytotoxicity. The photoproperties of the chlorin moiety are also conserved, with comparable singlet oxygen quantum yields found to the free chlorin

Flexible synthesis of cationic peptide-porphyrin derivatives for light-triggered drug delivery and photodynamic therapy

Efficient syntheses of cell-penetrating peptide-porphyrin conjugates are described using a variety of bioconjugation chemistries. This provides a flexible means to convert essentially hydrophobic tetrapyrolle photosensitisers into amphiphilic derivatives which are well-suited for use in light-triggered drug delivery by photochemical internalisation (PCI) and targeted photodynamic therapy (PDT)

Sentinel hospital-based surveillance of Rotavirus diarrhea in Iran

Background. Rotavirus is the most common causes of severe, acute diarrhea during childhood and is an important cause of morbidity and mortality in developing countries. We established active hospital-based surveillance of childhood diarrhea to assess the scope of severe rotavirus disease in Iran. Methods. From May 2006 through April 2007, prospective surveillance of rotavirus diarrhea among children aged <5 years was conducted in 5 sentinel hospitals in Iran. Stool samples were tested for rotavirus using a commercially available enzyme immunoassay, and rotavirus-positive samples were genotyped using reverse-transcriptase polymerase chain reaction. Results. Of 2198 children admitted to the hospital for acute gastroenteritis, 1298 (59.1%) had stool samples test positive for rotavirus by enzyme immunoassay. Of the rotavirus episodes, 85% occurred during the first 2 years of life, with the peak prevalence of severe rotavirus disease occurring from September through January. Among the 110 rotavirus-positive samples that were genotyped, G4P[8] was the most commonly detected rotavirus genotype (30.9% of strains). Other commonly detected genotypes included P[8] with G nontypeable (21.8%), G4 with P nontypeable (13.6%), G1[P8] (10.9%), and G2[P4] (5.5%). Conclusions. Rotavirus is the most common cause of severe diarrhea in Iran, which indicates that safe and effective rotavirus vaccination in Iran is a public health priority. © 2009 by the Infectious Diseases Society of America. All rights reserved

Cetuximab-Ag₂S quantum dots for fluorescence imaging and highly effective combination of ALA-based photodynamic/chemo-therapy of colorectal cancer cells

Colorectal cancer (CRC) has a poor prognosis and urgently needs better therapeutic approaches. 5-Aminolevulinic acid (ALA) induced protoprophyrin IX (PpIX) based photodynamic therapy (PDT) is already approved in the clinic for several cancers but not yet well investigated for CRC. Currently, systemic administration of ALA offers a limited degree of tumour selectivity, except for intracranial tumours, limiting its wider use in the clinic. Combination of effective ALA-PDT with chemotherapy may provide a promising alternative approach for CRC treatment. Herein, theranostic Ag2S quantum dots (AS-2MPA) optically trackable in near-infrared (NIR), conjugated with endothelial growth factor receptor (EGFR) targeting Cetuximab (Cet) and loaded with ALA for PDT monotherapy or ALA/5-fluorouracil (5FU) for the combination therapy is proposed for enhanced treatment of EGFR(+) CRC. AS-2MPA-Cet endowed excellent targeting of the high EGFR expressing cells and showed a strong intracellular signal for NIR optical detection in a comparative study performed on SW480, HCT116, and HT29 cells, which are high, medium and low EGFR expressers. Targeting provided enhanced uptake of the ALA loaded nanoparticles by strong EGFR expressing cells and formation of higher levels of PpIX. Cells also differ in their efficiency to convert ALA to PpIX, and SW480 was the best, followed by HT29, while HCT116 were determined as unsuitable for ALA-PDT. The therapeutic efficacy was evaluated in 2D cell cultures and 3D spheroids of SW480 and HT29 cells using AS-2MPA with either electrostatically loaded, hydrazone or amide linked ALA to achieve different levels of pH or enzyme sensitive release. Most effective phototoxicity was observed in SW480 cells using AS-2MPA-ALA-electrostatic-Cet due enhanced uptake of the particles, fast ALA release and effective ALA-to-PpIX conversion. Targeted delivery reduced the effective ALA concentration significantly which was further reduced with codelivery of 5FU. Delivery of ALA via covalent linkage was also effective for PDT, but required longer incubation time for the release of ALA in therapeutic doses. Phototoxicity was correlated with high levels of reactive oxygen species (ROS) and apoptotic/necrotic cell death. Hence, both AS-2MPA-ALA-Cet based PDT and AS-2MPA-ALA-Cet-5FU based Chemo/PDT combination therapy coupled with strong NIR tracking of the nanoparticles demonstrate an exceptional therapeutic effect on CRC cells and an excellent potential for synergistic multistage tumour targeting therapy