Mimicking subsecond neurotransmitter dynamics with femtosecond laser stimulated nanosystems

Existing nanoscale chemical delivery systems target diseased cells over long, sustained periods of time, typically through one-time, destructive triggering. Future directions lie in the development of fast and robust techniques capable of reproducing the pulsatile chemical activity of living organisms, thereby allowing us to mimic biofunctionality. Here, we demonstrate that by applying programmed femtosecond laser pulses to robust, nanoscale liposome structures containing dopamine, we achieve sub-second, controlled release of dopamine – a key neurotransmitter of the central nervous system – thereby replicating its release profile in the brain. The fast delivery system provides a powerful new interface with neural circuits and to the larger range of biological functions that operate on this short timescale

Dynamic control of neurochemical release with ultrasonically-sensitive nanoshell-tethered liposomes

The unique surface plasmon resonance of hollow gold nanoshells can be used to achieve drug release from liposomes upon laser stimulation, and adapted to mimic the intricate dynamics of neurotransmission ex vivo in brain preparations. However, to induce a physiological response in vivo requires the degree of temporal precision afforded by laser stimulation, but with a greater depth of penetration through tissue. Here we report that the attachment of hollow gold nanoshells to the surface of robust liposomes results in a construct that is highly sensitive to ultrasonic stimulation. The resulting construct can be remotely triggered by low intensity, therapeutic ultrasound. To our knowledge, this is the first example of nanoparticle-liposome system that can be activated by both laser and acoustic stimulation. The system is capable of encapsulating the neurochemical dopamine, and repeatedly releasing small amounts on-demand in a circulating environment, allowing for precise spatiotemporal control over the release profile

Enhanced melioidosis surveillance in patients attending four tertiary hospitals in Yangon, Myanmar.

Abstract To investigate the current epidemiology of melioidosis in Yangon, Myanmar, between June 2017 and May 2019 we conducted enhanced surveillance for melioidosis in four tertiary hospitals in Yangon, where the disease was first discovered in 1911. Oxidase-positive Gram-negative rods were obtained from the microbiology laboratories and further analysed at the Department of Medical Research. Analysis included culture on Ashdown agar, the three disc sensitivity test (gentamicin, colistin and co-amoxiclav), latex agglutination, API 20 NE, antibiotic susceptibility testing, and a subset underwent molecular confirmation with a Burkholderia pseudomallei specific assay. Twenty one of 364 isolates (5.7%) were confirmed as B. pseudomallei and were mostly susceptible to the antibiotics used in standard therapy for melioidosis. Ten patients were from Yangon Region, nine were from Ayeyarwaddy region, and one each was from Kayin and Rakhine States. A history of soil contact was given by seven patients, five had diabetes mellitus and one had renal insufficiency. The patients presented with septicaemia (12 cases), pneumonia (three cases), urinary tract infection (two cases) and wound infection (four cases). Eighteen patients survived to hospital discharge. This study highlights the likelihood that melioidosis may be far more common, but underdiagnosed, in more rural parts of Myanmar as in other countries in SE Asia.</jats:p

Melioidosis in Myanmar

Sporadic cases of melioidosis have been diagnosed in Myanmar since the disease was first described in Yangon in 1911. Published and unpublished cases are summarized here, along with results from environmental and serosurveys. A total of 298 cases have been reported from seven states or regions between 1911 and 2018, with the majority of these occurring before 1949. Findings from soil surveys confirm the presence of Burkholderia pseudomallei in the environment in all three regions examined. The true epidemiology of the disease in Myanmar is unknown. Important factors contributing to the current gaps in knowledge are lack of awareness among clinicians and insufficient laboratory diagnostic capacity in many parts of the country. This is likely to have led to substantial under-reporting