An Overview of Nanocarrier-Based Adjuvants for Vaccine Delivery

The development of vaccines is one of the most significant medical accomplishments which has helped to eradicate a large number of diseases. It has undergone an evolutionary process from live attenuated pathogen vaccine to killed whole organisms or inactivated toxins (toxoids), each of them having its own advantages and disadvantages. The crucial parameters in vaccination are the generation of memory response and protection against infection, while an important aspect is the effective delivery of antigen in an intelligent manner to evoke a robust immune response. In this regard, nanotechnology is greatly contributing to developing efficient vaccine adjuvants and delivery systems. These can protect the encapsulated antigen from the host’s in-vivo environment and releasing it in a sustained manner to induce a long-lasting immunostimulatory effect. In view of this, the present review article summarizes nanoscale-based adjuvants and delivery vehicles such as viral vectors, virus-like particles and virosomes; non-viral vectors namely nanoemulsions, lipid nanocarriers, biodegradable and non-degradable nanoparticles, calcium phosphate nanoparticles, colloidally stable nanoparticles, proteosomes; and pattern recognition receptors covering c-type lectin receptors and toll-like receptors

Haemostasis in Open Carpal Tunnel Release: Tourniquet vs Local Anaesthetic and Adrenaline

Open carpal tunnel release is one of the commonest performed procedures in hand surgery. We performed a prospective randomised control trial to compare the efficacy and patient satisfaction of the traditional arm tourniquet versus infiltration of adrenaline and local anaesthetic solution to achieve haemostasis during the procedure. Using a combination of objective and subjective measures we concluded that infiltration of local anaesthetic and adrenaline not only provided adequate haemostasis but also provided a significantly more tolerable experience for the patient during the procedure

Haemostasis in Open Carpal Tunnel Release: Tourniquet vs Local Anaesthetic and Adrenaline

Open carpal tunnel release is one of the commonest performed procedures in hand surgery. We performed a prospective randomised control trial to compare the efficacy and patient satisfaction of the traditional arm tourniquet versus infiltration of adrenaline and local anaesthetic solution to achieve haemostasis during the procedure. Using a combination of objective and subjective measures we concluded that infiltration of local anaesthetic and adrenaline not only provided adequate haemostasis but also provided a significantly more tolerable experience for the patient during the procedure

Surfactant protein D inhibits HIV-1 infection of target cells via interference with gp120-CD4 interaction and modulates pro-inflammatory cytokine production

© 2014 Pandit et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.Surfactant Protein SP-D, a member of the collectin family, is a pattern recognition protein, secreted by mucosal epithelial cells and has an important role in innate immunity against various pathogens. In this study, we confirm that native human SP-D and a recombinant fragment of human SP-D (rhSP-D) bind to gp120 of HIV-1 and significantly inhibit viral replication in vitro in a calcium and dose-dependent manner. We show, for the first time, that SP-D and rhSP-D act as potent inhibitors of HIV-1 entry in to target cells and block the interaction between CD4 and gp120 in a dose-dependent manner. The rhSP-D-mediated inhibition of viral replication was examined using three clinical isolates of HIV-1 and three target cells: Jurkat T cells, U937 monocytic cells and PBMCs. HIV-1 induced cytokine storm in the three target cells was significantly suppressed by rhSP-D. Phosphorylation of key kinases p38, Erk1/2 and AKT, which contribute to HIV-1 induced immune activation, was significantly reduced in vitro in the presence of rhSP-D. Notably, anti-HIV-1 activity of rhSP-D was retained in the presence of biological fluids such as cervico-vaginal lavage and seminal plasma. Our study illustrates the multi-faceted role of human SPD against HIV-1 and potential of rhSP-D for immunotherapy to inhibit viral entry and immune activation in acute HIV infection. © 2014 Pandit et al.The work (Project no. 2011-16850) was supported by Medical Innovation Fund of Indian Council of Medical Research, New Delhi, India (www.icmr.nic.in/)

Can cognitive psychological research on reasoning enhance the discussion around moral judgments?

In this article we will demonstrate how cognitive psychological research on reasoning and decision making could enhance discussions and theories of moral judgments. In the first part, we will present recent dual-process models of moral judgments and describe selected studies which support these approaches. However, we will also present data that contradict the model predictions, suggesting that approaches to moral judgment might be more complex. In the second part, we will show how cognitive psychological research on reasoning might be helpful in understanding moral judgments. Specifically, we will highlight approaches addressing the interaction between intuition and reflection. Our data suggest that a sequential model of engaging in deliberation might have to be revised. Therefore, we will present an approach based on Signal Detection Theory and on intuitive conflict detection. We predict that individuals arrive at the moral decisions by comparing potential action outcomes (e.g., harm caused and utilitarian gain) simultaneously. The response criterion can be influenced by intuitive processes, such as heuristic moral value processing, or considerations of harm caused

A survey on knowledge and self-reported formula handling practices of parents and child care workers in Palermo, Italy

Powdered infant formula (PIF) is not a sterile product, but this information appears to be poorly diffused among child caregivers. Parents and child care workers may behave in an unsafe manner when handling PIF. Methods: This study involved parents and child care workers in the 24 municipal child care centres of Palermo. Knowledge and self-reported practices about PIF handling were investigated by a structured questionnaire. A Likert scale was used to measure the strength of the respondent's feelings. Association of knowledge and self-reported practices with demographic variables was also evaluated. Results: 42.4% of parents and 71.0% of child care workers filled in the questionnaire. Significant differences were found between parents and child care workers for age and education. 73.2% of parents and 84.4% of child care workers were confident in sterility of PIF. Generally, adherence to safe procedures when reconstituting and handling PIF was more frequently reported by child care workers who, according to the existing legislation, are regularly subjected to a periodic training on food safety principles and practices. Age and education significantly influenced the answers to the questionnaire of both parents and child care workers. Conclusion: The results of the study reveal that parents and child care workers are generally unaware that powdered formulas may contain viable microorganisms. However, child care workers consistently chose safer options than parents when answering the questions about adherence to hygienic practices. At present it seems unfeasible to produce sterile PIF, but the risk of growth of hazardous organisms in formula at the time of administration should be minimized by promoting safer behaviours among caregivers to infants in both institutional settings and home. \ua9 2009 Calamusa et al; licensee BioMed Central Ltd

Novel Aptamer-Nanoparticle Bioconjugates Enhances Delivery of Anticancer Drug to MUC1-Positive Cancer Cells In Vitro

MUC1 protein is an attractive target for anticancer drug delivery owing to its overexpression in most adenocarcinomas. In this study, a reported MUC1 protein aptamer is exploited as the targeting agent of a nanoparticle-based drug delivery system. Paclitaxel (PTX) loaded poly (lactic-co-glycolic-acid) (PLGA) nanoparticles were formulated by an emulsion/evaporation method, and MUC1 aptamers (Apt) were conjugated to the particle surface through a DNA spacer. The aptamer conjugated nanoparticles (Apt-NPs) are about 225.3 nm in size with a stable in vitro drug release profile. Using MCF-7 breast cancer cell as a MUC1-overexpressing model, the MUC1 aptamer increased the uptake of nanoparticles into the target cells as measured by flow cytometry. Moreover, the PTX loaded Apt-NPs enhanced in vitro drug delivery and cytotoxicity to MUC1+ cancer cells, as compared with non-targeted nanoparticles that lack the MUC1 aptamer (P<0.01). The behavior of this novel aptamer-nanoparticle bioconjugates suggests that MUC1 aptamers may have application potential in targeted drug delivery towards MUC1-overexpressing tumors

Using the SaTScan method to detect local malaria clusters for guiding malaria control programmes

Mpumalanga Province, South Africa is a low malaria transmission area that is subject to malaria epidemics. SaTScan methodology was used by the malaria control programme to detect local malaria clusters to assist disease control planning. The third season for case cluster identification overlapped with the first season of implementing an outbreak identification and response system in the area. SaTScan™ software using the Kulldorf method of retrospective space-time permutation and the Bernoulli purely spatial model was used to identify malaria clusters using definitively confirmed individual cases in seven towns over three malaria seasons. Following passive case reporting at health facilities during the 2002 to 2005 seasons, active case detection was carried out in the communities, this assisted with determining the probable source of infection. The distribution and statistical significance of the clusters were explored by means of Monte Carlo replication of data sets under the null hypothesis with replications greater than 999 to ensure adequate power for defining clusters. SaTScan detected five space-clusters and two space-time clusters during the study period. There was strong concordance between recognized local clustering of cases and outbreak declaration in specific towns. Both Albertsnek and Thambokulu reported malaria outbreaks in the same season as space-time clusters. This synergy may allow mutual validation of the two systems in confirming outbreaks demanding additional resources and cluster identification at local level to better target resources. Exploring the clustering of cases assisted with the planning of public health activities, including mobilizing health workers and resources. Where appropriate additional indoor residual spraying, focal larviciding and health promotion activities, were all also carried out

The Terminal Immunoglobulin-Like Repeats of LigA and LigB of Leptospira Enhance Their Binding to Gelatin Binding Domain of Fibronectin and Host Cells

Leptospira spp. are pathogenic spirochetes that cause the zoonotic disease leptospirosis. Leptospiral immunoglobulin (Ig)-like protein B (LigB) contributes to the binding of Leptospira to extracellular matrix proteins such as fibronectin, fibrinogen, laminin, elastin, tropoelastin and collagen. A high-affinity Fn-binding region of LigB has been localized to LigBCen2, which contains the partial 11th and full 12th Ig-like repeats (LigBCen2R) and 47 amino acids of the non-repeat region (LigBCen2NR) of LigB. In this study, the gelatin binding domain of fibronectin was shown to interact with LigBCen2R (KD = 1.91±0.40 µM). Not only LigBCen2R but also other Ig-like domains of Lig proteins including LigAVar7'-8, LigAVar10, LigAVar11, LigAVar12, LigAVar13, LigBCen7'-8, and LigBCen9 bind to GBD. Interestingly, a large gain in affinity was achieved through an avidity effect, with the terminal domains, 13th (LigA) or 12th (LigB) Ig-like repeat of Lig protein (LigAVar7'-13 and LigBCen7'-12) enhancing binding affinity approximately 51 and 28 fold, respectively, compared to recombinant proteins without this terminal repeat. In addition, the inhibited effect on MDCKs cells can also be promoted by Lig proteins with terminal domains, but these two domains are not required for gelatin binding domain binding and cell adhesion. Interestingly, Lig proteins with the terminal domains could form compact structures with a round shape mediated by multidomain interaction. This is the first report about the interaction of gelatin binding domain of Fn and Lig proteins and provides an example of Lig-gelatin binding domain binding mediating bacterial-host interaction