Antimicrobial treatment of non-cystic fibrosis bronchiectasis

Bronchiectasis unrelated to cystic fibrosis is characterized by chronic wet or productive cough, recurrent exacerbations and irreversible bronchial dilatation. After antibiotics and vaccines became available and living standards in affluent countries improved, its resulting reduced prevalence meant bronchiectasis was considered an ‘orphan disease’. This perception has changed recently with increasing use of CT scans to diagnose bronchiectasis, including in those with severe chronic obstructive pulmonary disease or ‘difficult to control’ asthma, and adds to its already known importance in non-affluent countries and disadvantaged Indigenous communities. Following years of neglect, there is renewed interest in identifying the pathogenetic mechanisms of bronchiectasis, including the role of infection, and conducting clinical trials. This is providing much needed evidence to guide antimicrobial therapy, which has relied previously upon extrapolating treatments used in cystic fibrosis and chronic obstructive pulmonary disease. While many knowledge gaps and management challenges remain, the future is improving for patients with bronchiectasis.

Wolbachia reduces the transmission potential of Dengue-infected Aedes aegypti

BACKGROUND: Dengue viruses (DENV) are the causative agents of dengue, the world's most prevalent arthropod-borne disease with around 40% of the world's population at risk of infection annually. Wolbachia pipientis, an obligate intracellular bacterium, is being developed as a biocontrol strategy against dengue because it limits replication of the virus in the mosquito. The Wolbachia strain wMel, which has been introduced into the mosquito vector, Aedes aegypti, has been shown to invade and spread to near fixation in field releases. Standard measures of Wolbachia's efficacy for blocking virus replication focus on the detection and quantification of virus in mosquito tissues. Examining the saliva provides a more accurate measure of transmission potential and can reveal the extrinsic incubation period (EIP), that is, the time it takes virus to arrive in the saliva following the consumption of DENV viremic blood. EIP is a key determinant of a mosquito's ability to transmit DENVs, as the earlier the virus appears in the saliva the more opportunities the mosquito will have to infect humans on subsequent bites. METHODOLOGY/PRINCIPAL FINDINGS: We used a non-destructive assay to repeatedly quantify DENV in saliva from wMel-infected and Wolbachia-free wild-type control mosquitoes following the consumption of a DENV-infected blood meal. We show that wMel lengthens the EIP, reduces the frequency at which the virus is expectorated and decreases the dengue copy number in mosquito saliva as compared to wild-type mosquitoes. These observations can at least be partially explained by an overall reduction in saliva produced by wMel mosquitoes. More generally, we found that the concentration of DENV in a blood meal is a determinant of the length of EIP, saliva virus titer and mosquito survival. CONCLUSIONS/SIGNIFICANCE: The saliva-based traits reported here offer more disease-relevant measures of Wolbachia's effects on the vector and the virus. The lengthening of EIP highlights another means, in addition to the reduction of infection frequencies and DENV titers in mosquitoes, by which Wolbachia should operate to reduce DENV transmission in the field.

Graphene-covered perovskites: An effective strategy to enhance light absorption and resist moisture degradation

The long-term stability of methylammonium lead triiodide (MAPbI3) perovskite in moist environments is a paramount challenge to realise the commercialization of perovskite solar cells. In an attempt to address this concern, we have carried out systematic first-principles studies on the MAPbI3 perovskite with a hydrophobic graphene layer interfaced as a water barrier. We find there is a charge transfer at the graphene/MAPbI3 interface and electrons can be excited from graphene into the perovskite surface, leading to well separated electron–hole pairs, i.e. reduced recombination. By studying the optical properties, we find the hybrid graphene/MAPbI3 nanocomposite displays enhanced light absorption compared with the pristine MAPbI3. Furthermore, from an ab initio molecular dynamics simulation, the graphene/MAPbI3 nanocomposite is confirmed to be able to resist the reaction with water molecules, highlighting a great advantage of this nanocomposite in promoting long-term photovoltaic performance.

Specific rolling circle amplification of low-copy human polyomaviruses BKV, HPyV6, HPyV7, TSPyV, and STLPyV

Eleven new human polyomaviruses have been recently discovered, yet for most of these viruses, little is known of their biology and clinical impact. Rolling circle amplification (RCA) is an ideal method for the amplification of the circular polyomavirus genome due to its high fidelity amplification of circular DNA. In this study, a modified RCA method was developed to selectively amplify a range of polyomavirus genomes. Initial evaluation showed a multiplexed temperature-graded reaction profile gave the best yield and sensitivity in amplifying BK polyomavirus in a background of human DNA, with up to 1 × 10(8)-fold increases in viral genomes from as little as 10 genome copies per reaction. Furthermore, the method proved to be more sensitive and provided a 200-fold greater yield than that of random hexamers based standard RCA. Application of the method to other novel human polyomaviruses showed successful amplification of TSPyV, HPyV6, HPyV7, and STLPyV from low-viral load positive clinical samples, with viral genome enrichment ranging from 1 × 10(8) up to 1 × 10(10). This directed RCA method can be applied to selectively amplify other low-copy polyomaviral genomes from a background of competing non-specific DNA, and is a useful tool in further research into the rapidly expanding Polyomaviridae family.

Advances in nano-scaled biosensors for biomedical applications

Recently, a growing amount of attention has been focused on the utility of biosensors for biomedical applications. Combined with nanomaterials and nanostructures, nano-scaled biosensors are installed for biomedical applications, such as pathogenic bacteria monitoring, virus recognition, disease biomarker detection, among others. These nano-biosensors offer a number of advantages and in many respects are ideally suited to biomedical applications, which could be made as extremely flexible devices, allowing biomedical analysis with speediness, excellent selectivity and high sensitivity. This minireview discusses the literature published in the latest years on the advances in biomedical applications of nano-scaled biosensors for disease bio-marking and detection, especially in bio-imaging and the diagnosis of pathological cells and viruses, monitoring pathogenic bacteria, thus providing insight into the future prospects of biosensors in relevant clinical applications.

A native Wolbachia Endosymbiont does not limit Dengue virus infection in the mosquito Aedes notoscriptus (Diptera: Culicidae)

The endosymbiotic bacterium Wolbachia pipientis infects many species of insects and has been transinfected into the mosquito Aedes aegypti (L.), the primary vector of dengue virus (DENV). Recently, it has been shown that Wolbachia blocks the replication and transmission of RNA viruses, such as DENV, in a number of mosquito species including Ae. aegypti and Aedes albopictus (Skuse), which is naturally infected with Wolbachia and considered a secondary vector for DENV. The mosquito species Aedes notoscriptus (Skuse) is highly prevalent in Australia, including in areas where DENV outbreaks have been recorded. The mosquito has been implicated in the transmission of Ross River and Barmah Forest viruses, but not DENV. We investigated whether Wolbachia naturally infects this mosquito species and whether it has an impact on the ability of Ae. notoscriptus to transmit DENV. We show, for the first time, that Ae. notoscriptus is naturally infected with a strain of Wolbachia that belongs to supergroup B and is localized only in the ovaries. However, Wolbachia infection in Ae. notoscriptus did not induce resistance to DENV and had no effect on overall DENV infection rate or titer. The presence of a native Wolbachia in Ae. notoscriptus cannot explain why this mosquito is an ineffective vector of DENV.

Amber teething necklaces – medical marvel or maternal myth?

BACKGROUND: Baltic amber-bead necklaces or bracelets are commonly used for managing teething symptoms in infants. The effectiveness of these beads is claimed to be from succinic acid release (a compound with analgesic and anti-inflammatory properties), which is then absorbed through the skin. AIM: To investigate whether Baltic amber teething necklaces purchased in Australia contained succinic acid, and to quantify succinic acid release from the beads. METHODS: Infrared spectroscopy was used to confirm that the teething necklaces were made of Baltic amber. The amount of succinic acid contained within the beads was quantified, and succinic acid release from intact beads was measured in phosphate buffered saline (PBS) pH 5.5 or octanol to simulate aqueous or oily skin environments. RESULTS: Each necklace (33 beads in length) contained 19.17±4.89 mg of succinic acid (mean±se). Over a 6-month period, no succinic acid was detected in PBS, while 0.13±0.09 mg of succinic acid per necklace was released in octanol. Only one replicate of amber beads in octanol released succinic acid, and they had fragmented, with shards free-floating in the solvent. DISCUSSION: It is likely succinic acid was only detected because the beads were breaking down in octanol, which does not occur when worn around the neck of a child. Furthermore, the hydrophilic properties of succinic acid would not favour its absorption across hydrophobic layers of the skin and into the bloodstream. CONCLUSION: While the teething necklaces do contain small quantities of succinic acid, it is highly unlikely to be released from intact beads.

Catalyst-free plasma enhanced growth of graphene from sustainable sources

Details of a fast and sustainable bottom-up process to grow large area high quality graphene films without the aid of any catalyst are reported in this paper. We used Melaleuca alternifolia, a volatile natural extract from tea tree plant as the precursor. The as-fabricated graphene films yielded a stable contact angle of 135°, indicating their potential application in very high hydrophobic coatings. The electronic devices formed by sandwiching pentacene between graphene and aluminum films demonstrated memristive behavior, and hence, these graphene films could find use in nonvolatile memory devices also.

Wetting, solubility and chemical characteristics of plasma-polymerized 1-isopropyl-4-methyl-1,4-cyclohexadiene thin films

Investigations on the wetting, solubility and chemical composition of plasma polymer thin films provide an insight into the feasibility of implementing these polymeric materials in organic electronics, particularly where wet solution processing is involved. In this study, thin films were prepared from 1-isopropyl-4-methyl-1,4-cyclohexadiene (γ-Terpinene) using radio frequency (RF) plasma polymerization. FTIR showed the polymers to be structurally dissimilar to the original monomer and highly cross-linked, where the loss of original functional groups and the degree of cross-linking increased with deposition power. The polymer surfaces were hydrocarbon-rich, with oxygen present in the form of O–H and C=O functional groups. The oxygen content decreased with deposition power, with films becoming more hydrophobic and, thus, less wettable. The advancing and receding contact angles were investigated, and the water advancing contact angle was found to increase from 63.14° to 73.53° for thin films prepared with an RF power of 10 W to 75 W. The wetting envelopes for the surfaces were constructed to enable the prediction of the surfaces’ wettability for other solvents. The effect of roughness on the wetting behaviour of the films was insignificant. The polymers were determined to resist solubilization in solvents commonly used in the deposition of organic semiconducting layers, including chloroform and chlorobenzene, with higher stability observed in films fabricated at higher RF power.

Clinical tips: Food poisoning

Food poisoning is used to describe a range of illnesses caused by drinking or eating contaminated drink or food. Infectious pathogens include bacteria, viruses, parasites, or their toxins, though food poisoning can also be a result of eating poisonous plants e.g. some mushrooms, or animals e.g. puffer fish. Common symptoms include nausea, vomiting, watery diarrhoea, abdominal pain and cramps, and fevers, though these will vary depending on the causative pathogen or toxin. Symptoms can start within hours of eating contaminated food, or may begin days or weeks later. Most food poisoning is mild in nature, lasts for several hours to a few days, and generally resolves without treatment. However, some cases of food poisoning can also be extremely severe, with people requiring medical attention or admission to hospital...

Impacts of El Niño southern oscillation and Indian Ocean dipole on dengue incidence in Bangladesh

Dengue dynamics are driven by complex interactions between hosts, vectors and viruses that are influenced by environmental and climatic factors. Several studies examined the role of El Niño Southern Oscillation (ENSO) in dengue incidence. However, the role of Indian Ocean Dipole (IOD), a coupled ocean atmosphere phenomenon in the Indian Ocean, which controls the summer monsoon rainfall in the Indian region, remains unexplored. Here, we examined the effects of ENSO and IOD on dengue incidence in Bangladesh. According to the wavelet coherence analysis, there was a very weak association between ENSO, IOD and dengue incidence, but a highly significant coherence between dengue incidence and local climate variables (temperature and rainfall). However, a distributed lag nonlinear model (DLNM) revealed that the association between dengue incidence and ENSO or IOD were comparatively stronger after adjustment for local climate variables, seasonality and trend. The estimated effects were nonlinear for both ENSO and IOD with higher relative risks at higher ENSO and IOD. The weak association between ENSO, IOD and dengue incidence might be driven by the stronger effects of local climate variables such as temperature and rainfall. Further research is required to disentangle these effects.

Recent insights into microbial triggers of interleukin-10 production in the host and the impact on infectious disease pathogenesis

Since its initial description as a Th2-cytokine antagonistic to interferon-alpha and granulocyte-macrophage colony-stimulating factor, many studies have shown various anti-inflammatory actions of interleukin-10 (IL-10), and its role in infection as a key regulator of innate immunity. Studies have shown that IL-10 induced in response to microorganisms and their products plays a central role in shaping pathogenesis. IL-10 appears to function as both sword and shield in the response to varied groups of microorganisms in its capacity to mediate protective immunity against some organisms but increase susceptibility to other infections. The nature of IL-10 as a pleiotropic modulator of host responses to microorganisms is explained, in part, by its potent and varied effects on different immune effector cells which influence antimicrobial activity. A new understanding of how microorganisms trigger IL-10 responses is emerging, along with recent discoveries of how IL-10 produced during disease might be harnessed for better protective or therapeutic strategies. In this review, we summarize studies from the past 5 years that have reported the induction of IL-10 by different classes of pathogenic microorganisms, including protozoa, nematodes, fungi, viruses and bacteria and discuss the impact of this induction on the persistence and/or clearance of microorganisms in the host.

The extremophile Nicotiana benthamiana has traded viral defence for early vigour

A single lineage of Nicotiana benthamiana is widely used as a model plant1 and has been instrumental in making revolutionary discoveries about RNA interference (RNAi), viral defence and vaccine production. It is peerless in its susceptibility to viruses and its amenability in transiently expressing transgenes2,3. These unparalleled characteristics have been associated both positively and negatively with a disruptive insertion in the RNA-dependent RNA polymerase 1 gene, Rdr14–6. For a plant so routinely used in research, the origin, diversity and evolution of the species, and the basis of its unusual abilities, have been relatively unexplored. Here, by comparison with wild accessions from across the spectrum of the species’ natural distribution, we show that the laboratory strain of N. benthamiana is an extremophile originating from a population that has retained a mutation in Rdr1 for ∼0.8 Myr and thereby traded its defence capacity for early vigour and survival in the extreme habitat of central Australia. Reconstituting Rdr1 activity in this isolate provided protection. Silencing the functional allele in a wild strain rendered it hypersusceptible and was associated with a doubling of seed size and enhanced early growth rate. These findings open the way to a deeper understanding of the delicate balance between protection and vigour.

Stable expression of silencing-suppressor protein enhances the performance and longevity of an engineered metabolic pathway

Transgenic engineering of plants is important in both basic and applied research. However, the expression of a transgene can dwindle over time as the plant's small (s)RNA-guided silencing pathways shut it down. The silencing pathways have evolved as antiviral defence mechanisms, and viruses have co-evolved viral silencing-suppressor proteins (VSPs) to block them. Therefore, VSPs have been routinely used alongside desired transgene constructs to enhance their expression in transient assays. However, constitutive, stable expression of a VSP in a plant usually causes pronounced developmental abnormalities, as their actions interfere with endogenous microRNA-regulated processes, and has largely precluded the use of VSPs as an aid to stable transgene expression. In an attempt to avoid the deleterious effects but obtain the enhancing effect, a number of different VSPs were expressed exclusively in the seeds of Arabidopsis thaliana alongside a three-step transgenic pathway for the synthesis of arachidonic acid (AA), an ω-6 long chain polyunsaturated fatty acid. Results from independent transgenic events, maintained for four generations, showed that the VSP-AA-transformed plants were developmentally normal, apart from minor phenotypes at the cotyledon stage, and could produce 40% more AA than plants transformed with the AA transgene cassette alone. Intriguingly, a geminivirus VSP, V2, was constitutively expressed without causing developmental defects, as it acts on the siRNA amplification step that is not part of the miRNA pathway, and gave strong transgene enhancement. These results demonstrate that VSP expression can be used to protect and enhance stable transgene performance and has significant biotechnological application.

Environmental applications of inorganic-organic clays for recalcitrant organic pollutants removal: Bisphenol A

Bisphenol-A (BPA) adsorption onto inorganic-organic clays (IOCs) was investigated. For this purpose, IOCs synthesised using octadecyltrimethylammonium bromide (ODTMA, organic modifier) and hydroxy aluminium (Al13, inorganic modifier) were used. Three intercalation methods were employed with varying ODTMA concentration in the synthesis of IOCs. Molecular interactions of clay surfaces with ODTMA and Al13 and their arrangements within the interlayers were determined using Fourier transform infrared spectroscopy (FTIR). Surface area and porous structure of IOCs were determined by applying Brunauer, Emmett, and Teller (BET) method to N2 adsorption-desorption isotherms. Surface area decreased upon ODTMA intercalation while it increased with Al13 pillaring. As a result, BET specific surface area of IOCs was considerably higher than those of organoclays. Initial concentration of BPA, contact time and adsorbent dose significantly affected BPA adsorption into IOCs. Pseudo-second order kinetics model is the best fit for BPA adsorption into IOCs. Both Langmuir and Freundlich adsorption isotherms were applicable for BPA adsorption (R2 > 0.91) for IOCs. Langmuir maximum adsorption capacity for IOCs was as high as 109.89 mg g‒1 and it was closely related to the loaded ODTMA amount into the clay. Hydrophobic interactions between long alkyl chains of ODTMA and BPA are responsible for BPA adsorption into IOCs.