Opportunities for topical antimicrobial therapy: permeation of canine skin by fusidic acid

BACKGROUND: Staphylococcal infection of the canine epidermis and hair follicle is amongst the commonest reasons for antimicrobial prescribing in small animal veterinary practice. Topical therapy with fusidic acid (FA) is an attractive alternative to systemic therapy based on low minimum inhibitory concentrations (MICs, commonly <0.03 mg/l) documented in canine pathogenic staphylococci, including strains of MRSA and MRSP (methicillin-resistant Staphylococcus aureus and S. pseudintermedius). However, permeation of canine skin by FA has not been evaluated in detail. This study aimed to define the degree and extent of FA permeation in canine skin in vitro from two sites with different hair follicle density following application of a licensed ophthalmic formulation that shares the same vehicle as an FA-betamethasone combination product approved for dermal application in dogs. Topical FA application was modelled using skin held in Franz-type diffusion cells. Concentrations of FA in surface swabs, receptor fluid, and transverse skin sections of defined anatomical depth were determined using high-performance liquid chromatography and ultraviolet (HPLC-UV) analysis. RESULTS: The majority of FA was recovered by surface swabs after 24 h, as expected (mean ± SEM: 76.0 ± 17.0%). FA was detected within 424/470 (90%) groups of serial sections of transversely cryotomed skin containing follicular infundibula, but never in 48/48 (100%) groups of sections containing only deeper follicular structures, nor in receptor fluid, suggesting that FA does not permeate beyond the infundibulum. The FA concentration (mean ± SEM) in the most superficial 240 μm of skin was 2000 ± 815 μg/g. CONCLUSIONS: Topically applied FA can greatly exceed MICs for canine pathogenic staphylococci at the most common sites of infection. Topical FA therapy should now be evaluated using available formulations in vivo as an alternative to systemic therapy for canine superficial bacterial folliculitis.Peer reviewedFinal Published versio

Delayed reperfusion deficits after experimental stroke account for increased pathophysiology.

Cerebral blood flow and oxygenation in the first few hours after reperfusion following ischemic stroke are critical for therapeutic interventions but are not well understood. We investigate changes in oxyhemoglobin (HbO(2)) concentration in the cortex during and after ischemic stroke, using multispectral optical imaging in anesthetized mice, a remote filament to induce either 30 minute middle cerebral artery occlusion (MCAo), sham surgery or anesthesia alone. Immunohistochemistry establishes cortical injury and correlates the severity of damage with the change of oxygen perfusion. All groups were imaged for 6 hours after MCAo or sham surgery. Oxygenation maps were calculated using a pathlength scaling algorithm. The MCAo group shows a significant drop in HbO(2) during occlusion and an initial increase after reperfusion. Over the subsequent 6 hours HbO(2) concentrations decline to levels below those observed during stroke. Platelets, activated microglia, interleukin-1α, evidence of BBB breakdown and neuronal stress increase within the stroked hemisphere and correlate with the severity of the delayed reperfusion deficit but not with the ΔHbO(2) during stroke. Despite initial restoration of HbO(2) after 30 min MCAo there is a delayed compromise that coincides with inflammation and could be a target for improved stroke outcome after thrombolysis

Species-level functional profiling of metagenomes and metatranscriptomes.

Functional profiles of microbial communities are typically generated using comprehensive metagenomic or metatranscriptomic sequence read searches, which are time-consuming, prone to spurious mapping, and often limited to community-level quantification. We developed HUMAnN2, a tiered search strategy that enables fast, accurate, and species-resolved functional profiling of host-associated and environmental communities. HUMAnN2 identifies a community's known species, aligns reads to their pangenomes, performs translated search on unclassified reads, and finally quantifies gene families and pathways. Relative to pure translated search, HUMAnN2 is faster and produces more accurate gene family profiles. We applied HUMAnN2 to study clinal variation in marine metabolism, ecological contribution patterns among human microbiome pathways, variation in species' genomic versus transcriptional contributions, and strain profiling. Further, we introduce 'contributional diversity' to explain patterns of ecological assembly across different microbial community types

Towards a large-scale quantum simulator on diamond surface at room temperature

Strongly-correlated quantum many-body systems exhibits a variety of exotic phases with long-range quantum correlations, such as spin liquids and supersolids. Despite the rapid increase in computational power of modern computers, the numerical simulation of these complex systems becomes intractable even for a few dozens of particles. Feynman's idea of quantum simulators offers an innovative way to bypass this computational barrier. However, the proposed realizations of such devices either require very low temperatures (ultracold gases in optical lattices, trapped ions, superconducting devices) and considerable technological effort, or are extremely hard to scale in practice (NMR, linear optics). In this work, we propose a new architecture for a scalable quantum simulator that can operate at room temperature. It consists of strongly-interacting nuclear spins attached to the diamond surface by its direct chemical treatment, or by means of a functionalized graphene sheet. The initialization, control and read-out of this quantum simulator can be accomplished with nitrogen-vacancy centers implanted in diamond. The system can be engineered to simulate a wide variety of interesting strongly-correlated models with long-range dipole-dipole interactions. Due to the superior coherence time of nuclear spins and nitrogen-vacancy centers in diamond, our proposal offers new opportunities towards large-scale quantum simulation at room temperatures

The emerging landscape of health research based on biobanks linked to electronic health records: Existing resources, statistical challenges, and potential opportunities

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/154448/1/sim8445_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/154448/2/sim8445.pd

A hypothetico-deductive approach to assessing the social function of chemical signalling in a non-territorial solitary carnivore

The function of chemical signalling in non-territorial solitary carnivores is still relatively unclear. Studies on territorial solitary and social carnivores have highlighted odour capability and utility, however the social function of chemical signalling in wild carnivore populations operating dominance hierarchy social systems has received little attention. We monitored scent marking and investigatory behaviour of wild brown bears Ursus arctos, to test multiple hypotheses relating to the social function of chemical signalling. Camera traps were stationed facing bear ‘marking trees’ to document behaviour by different age sex classes in different seasons. We found evidence to support the hypothesis that adult males utilise chemical signalling to communicate dominance to other males throughout the non-denning period. Adult females did not appear to utilise marking trees to advertise oestrous state during the breeding season. The function of marking by subadult bears is somewhat unclear, but may be related to the behaviour of adult males. Subadults investigated trees more often than they scent marked during the breeding season, which could be a result of an increased risk from adult males. Females with young showed an increase in marking and investigation of trees outside of the breeding season. We propose the hypothesis that females engage their dependent young with marking trees from a young age, at a relatively ‘safe’ time of year. Memory, experience, and learning at a young age, may all contribute towards odour capabilities in adult bears

Self-reported use of anti-malarial drugs and health facility management of malaria in Ghana

<p>Abstract</p> <p>Objective</p> <p>To assess the appropriateness of self-reported use of anti-malarial drugs prior to health facility attendance, and the management of malaria in two health facilities in Ghana.</p> <p>Method</p> <p>A structured questionnaire was used to collect data from 500 respondents who were diagnosed clinically and/or parasitologically for malaria at Agogo Presbyterian Hospital and Suntreso Polyclinic, both in the Ashanti Region of Ghana. Collected information included previous use of anti-malarial drugs prior to attending the health facilities, types of drugs used, how the drugs were used, and the sources of the drugs. In addition, the anti-malarial therapy given and outcomes at the two health facilities were assessed.</p> <p>Results</p> <p>Of the 500 patients interviewed, 17% had severe malaria, 8% had moderate to severe malaria and 75% had uncomplicated malaria. Forty three percent of the respondents had taken anti-malarial drugs within two weeks prior to hospital attendance. The most commonly used anti-malarials were chloroquine (76%), sulphadoxine-pyrimethamine (9%), herbal preparations (9%) and amodiaquine (6%). The sources of these medicines were licensed chemical sellers (50%), pharmacies (21%), neighbouring clinics (9%) or "other" sources (20%) including left-over medicines at home. One hundred and sixty three (77%) of the 213 patients who had used anti-malarial drugs prior to attending the health facilities, used the drugs inappropriately. At the health facilities, the anti-malarials were prescribed and used according to the national standard treatment guidelines with good outcomes.</p> <p>Conclusion</p> <p>Prevalence of inappropriate use of anti-malarials in the community in Ghana is high. There is need for enhanced public health education on home-based management of malaria and training for workers in medicine supply outlets to ensure effective use of anti-malaria drugs in the country.</p

Direct patterning of gold nanoparticles using flexographic printing for biosensing applications

In this paper, we have presented the use of flexographic printing techniques in the selective patterning of gold nanoparticles (AuNPs) onto a substrate. Highly uniform coverage of AuNPs was selectively patterned on the substrate surface, which was subsequently used in the development of a glucose sensor. These AuNPs provide a biocompatible site for the attachment of enzymes and offer high sensitivity in the detection of glucose due to their large surface to volume ratio. The average size of the printed AuNPs is less than 60 nm. Glucose sensing tests were performed using printed carbon-AuNP electrodes functionalized with glucose oxidase (GOx). The results showed a high sensitivity of 5.52 μA mM−1 cm−2 with a detection limit of 26 μM. We have demonstrated the fabrication of AuNP-based biosensors using flexographic printing, which is ideal for low-cost, high-volume production of the devices

Stigma and Self-Stigma in Addiction

Addictions are commonly accompanied by a sense of shame or self-stigmatization. Self-stigmatization results from public stigmatization in a process leading to the internalization of the social opprobrium attaching to the negative stereotypes associated with addiction. We offer an account of how this process works in terms of a range of looping effects, and this leads to our main claim that for a significant range of cases public stigma figures in the social construction of addiction. This rests on a social constructivist account in which those affected by public stigmatization internalize its norms. Stigma figures as part-constituent of the dynamic process in which addiction is formed. Our thesis is partly theoretical, partly empirical, as we source our claims about the process of internalization from interviews with people in treatment for substance use problems