Cancer-selective, single agent chemoradiosensitising gold nanoparticles

Two nanometre gold nanoparticles (AuNPs), bearing sugar moieties and/or thiol-polyethylene glycol-amine (PEG-amine), were synthesised and evaluated for their in vitro toxicity and ability to radiosensitise cells with 220 kV and 6 MV X-rays, using four cell lines representing normal and cancerous skin and breast tissues. Acute 3 h exposure of cells to AuNPs, bearing PEG-amine only or a 50:50 ratio of alpha-galactose derivative and PEG-amine resulted in selective uptake and toxicity towards cancer cells at unprecedentedly low nanomolar concentrations. Chemotoxicity was prevented by co-administration of N-acetyl cysteine antioxidant, or partially prevented by the caspase inhibitor Z-VAD-FMK. In addition to their intrinsic cancer-selective chemotoxicity, these AuNPs acted as radiosensitisers in combination with 220 kV or 6 MV X-rays. The ability of AuNPs bearing simple ligands to act as cancer-selective chemoradiosensitisers at low concentrations is a novel discovery that holds great promise in developing low-cost cancer nanotherapeutics

Microbial community succession on developing lesions on human enamel

Dental caries is one of the most common diseases in the world. However, our understanding of how the microbial community composition changes in vivo as caries develops is lacking.An in vivo model was used in a longitudinal cohort study to investigate shifts in the microbial community composition associated with the development of enamel caries.White spot lesions were generated in vivo on human teeth predetermined to be extracted for orthodontic reasons. The bacterial microbiota on sound enamel and on developing carious lesions were identified using the Human Oral Microbe Identification Microarray (HOMIM), which permits the detection of about 300 of the approximate 600 predominant bacterial species in the oral cavity.After only seven weeks, 75% of targeted teeth developed white spot lesions (8 individuals, 16 teeth). The microbial community composition of the plaque over white spot lesions differed significantly as compared to sound enamel. Twenty-five bacterial taxa, including Streptococcus mutans, Atopobium parvulum, Dialister invisus, and species of Prevotella and Scardovia, were significantly associated with initial enamel lesions. In contrast, 14 bacterial taxa, including species of Fusobacterium, Campylobacter, Kingella, and Capnocytophaga, were significantly associated with sound enamel.The bacterial community composition associated with the progression of enamel lesions is specific and much more complex than previously believed. This investigation represents one of the first longitudinally-derived studies for caries progression and supports microbial data from previous cross-sectional studies on the development of the disease. Thus, the in vivo experiments of generating lesions on teeth destined for extraction in conjunction with HOMIM analyses represent a valid model to study succession of supragingival microbial communities associated with caries development and to study efficacy of prophylactic and restorative treatments

Dengue Incidence in Urban and Rural Cambodia: Results from Population-Based Active Fever Surveillance, 2006–2008

Dengue is a major public health problem in South-East Asia. Several dengue vaccine candidates are now in late-stage development and are being evaluated in clinical trials. Accurate estimates of true dengue disease burden will become an important factor in the public-health decision-making process for endemic countries once safe and effective vaccines become available. However, estimates of the true disease incidence are difficult to make, because national surveillance systems suffer from disease under-recognition and reporting. Dengue is mainly reported among children, and in some countries, such as Cambodia, the national case definition only includes hospitalized children. This study used active, community-based surveillance of febrile illness coupled with laboratory testing for DENV infection to identify cases of dengue fever in rural and urban populations. We found a high burden of dengue in young children and late adolescents in both rural and urban communities at a magnitude greater than previously described. The study also confirmed the previously observed focal nature of dengue virus transmission

Ancient Antimicrobial Peptides Kill Antibiotic-Resistant Pathogens: Australian Mammals Provide New Options

Background: To overcome the increasing resistance of pathogens to existing antibiotics the 10× 20 Initiative declared the urgent need for a global commitment to develop 10 new antimicrobial drugs by the year 2020. Naturally occurring animal antibiotics are an obvious place to start. The recently sequenced genomes of mammals that are divergent from human and mouse, including the tammar wallaby and the platypus, provide an opportunity to discover novel antimicrobials. Marsupials and monotremes are ideal potential sources of new antimicrobials because they give birth to underdeveloped immunologically naïve young that develop outside the sterile confines of a uterus in harsh pathogen-laden environments. While their adaptive immune system develops innate immune factors produced either by the mother or by the young must play a key role in protecting the immune-compromised young. In this study we focus on the cathelicidins, a key family of antimicrobial peptide genes. Principal Finding: We identified 14 cathelicidin genes in the tammar wallaby genome and 8 in the platypus genome. The tammar genes were expressed in the mammary gland during early lactation before the adaptive immune system of the young develops, as well as in the skin of the pouch young. Both platypus and tammar peptides were effective in killing a broad range of bacterial pathogens. One potent peptide, expressed in the early stages of tammar lactation, effectively killed multidrug-resistant clinical isolates of Pseudomonas aeruginosa, Klebsiella pneumoniae and Acinetobacter baumannii. Conclusions and Significance: Marsupial and monotreme young are protected by antimicrobial peptides that are potent, broad spectrum and salt resistant. The genomes of our distant relatives may hold the key for the development of novel drugs to combat multidrug-resistant pathogens

Epilepsy Cambodia InterVention (ECIR): Résultats et enseignements

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Development of an interventional strategy for the management of epilepsy in South-East Asia.

International audienceBackgroundThe prevalence of epilepsy is 7.7‰ in Laos and 5.8‰ in Cambodia, and the treatment gap exceeds 90% inboth countries.ObjectiveOur research program aims to measure the effectiveness of two community-based health care approaches usingtwo different types of Domestic Health Visitors (DHV) trained to screen and follow patients with epilepsy (PWE):(1) in Laos, DHV were chosen from health center staff (2) in Cambodia, DHV were health volunteers residing inthe villages.Patients and Methods / Material and MethodsBetween 2015 and 2017, these two quasi-experimental studies were conducted in rural districts over a 12-months period comparing an intervention area and a control area. Our intervention included an Information,Education and Communication campaign, specific training of the DHV staff, and regular monitoring.In Laos, the treatment gap was reduced by 5.5% (20 to 43 cases under treatment of the 418 expected) in theintervention area versus 0.5% (21 to 25 cases under treatment of the 788 expected) in the control area(p<0.0001). In Cambodia, after a 6-month period (ongoing study) in area, it was reduced by 31.1% (0 to 55cases out of the 177 expected) in the intervention compared to a 7.0% decrease (0 to 23 cases out of the 327expected) in the control area (p<0.0001).ConclusionThe strategy is more successful when the DHV lives in the village where he/she is going to perform his/her duty.The results of the intervention in Laos have resulted in an Advocacy Policy Plan which has been favorablyreceived by the Lao Ministry of Health

Intervention strategy for the management of epilepsy in South-East Asia

International audiencePurpose:The prevalence of epilepsy is 7.7& in Laos and 5.8 & in Cambodia, the treatment gap exceeds 95% in both countries. Our researchprogram aims to measure the effectiveness of two new community-based health care approaches using two different types of Domestic HealthVisitors (DHV) trained to screen and follow patients with epilepsy (PWE): (1) in Laos DHV chosen from health center staff (2) an identicalstrategy in Cambodia where DHV duty was carried out by health volunteers residing in the villages.Method:Between 2015 and 2017, these two quasi-experimental studies were conducted in rural districts over a 12-months period comparing anintervention area and a control area. Our intervention included an Information, Education and Communication campaign, training of the DHVstaff, a number of surveys on general population about Knowledge, attitudes and practices (KAP) and regular monitoring.Results:In Laos after a 12-month intervention period, the treatment gap was reduced by 5.5% (20 to 43 cases under treatment of the 418expected) in the intervention vs. 0.5% (21 to 25 cases under treatment of the 788 expected) in the control area (p <0.0001). In Cambodia, after a6-month period in area with a treatment gap of 100%, he was reduced by 31.1% (55 cases out of the 177 expected) in the intervention compared toa 7.0% decrease (23 cases out of the 327 expected) in the control area (p <0.0001).Conclusion:The strategy is more successful when the DHV lives in the village where he/she is going to perform his/her duty. Observations on KAP in the general population and among health staff, in addition to the therapeutic pathway of PWE will enlighten our results. The results of the intervention in Laos have resulted in an Advocacy Policy Plan which has been favorably received by the Lao Ministry of Health

Carious Dentine Provides a Habitat for a Complex Array of Novel Prevotella-Like Bacteria

Previous analysis of the microbiology of advanced caries by culture and real-time PCR emphasized the high incidence and abundance of gram-negative anaerobic species, particularly Prevotella-like bacteria. The diversity of Prevotella-like bacteria was further explored by analyzing pooled bacterial DNA from lesions of carious dentine. This was achieved by amplification of a region of the 16S ribosomal DNA with a Prevotella genus-specific forward primer and a universal bacterial reverse primer, followed by cloning and sequencing. Cultured Prevotella species commonly associated with oral tissues constituted only 12% of the Prevotella clones isolated from advanced carious lesions. The remaining 88% consisted of a diverse range of phylotypes. These included five clusters of previously recognized but uncultured oral Prevotella spp. and a major cluster containing Prevotella-like bacteria most closely related to uncharacterized rumen bacteria. Cluster-specific primers were designed, and the numbers of bacteria within clusters were quantified by real-time PCR, confirming the abundance of these organisms. The data indicated that advanced dental caries provides a unique environment for a complex array of novel and uncultured Prevotella and Prevotella-like bacteria which, in some cases, may dominate the diverse polymicrobial community associated with the disease

Domestic health visitors (Village health volunteers) to improve access to care for people with epilepsy.

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