Transcription profiling reveals potential mechanisms of dysbiosis in the oral microbiome of rhesus macaques with chronic untreated SIV infection.

A majority of individuals infected with human immunodeficiency virus (HIV) have inadequate access to antiretroviral therapy and ultimately develop debilitating oral infections that often correlate with disease progression. Due to the impracticalities of conducting host-microbe systems-based studies in HIV infected patients, we have evaluated the potential of simian immunodeficiency virus (SIV) infected rhesus macaques to serve as a non-human primate model for oral manifestations of HIV disease. We present the first description of the rhesus macaque oral microbiota and show that a mixture of human commensal bacteria and "macaque versions" of human commensals colonize the tongue dorsum and dental plaque. Our findings indicate that SIV infection results in chronic activation of antiviral and inflammatory responses in the tongue mucosa that may collectively lead to repression of epithelial development and impact the microbiome. In addition, we show that dysbiosis of the lingual microbiome in SIV infection is characterized by outgrowth of Gemella morbillorum that may result from impaired macrophage function. Finally, we provide evidence that the increased capacity of opportunistic pathogens (e.g. E. coli) to colonize the microbiome is associated with reduced production of antimicrobial peptides

Physical characterization of Tobramycin Inhalation Powder: II. State Diagram of an Amorphous Engineered Particle

Tobramycin Inhalation Powder (TIP) is a spray-dried engineered particle formulation used in TOBI® Podhaler™, a drug/device combination for treatment of cystic fibrosis. A TIP particle consists of two phases: amorphous, glassy tobramycin sulfate and a gel-phase phospholipid (DSPC). The objective of this work was to characterize both the amorphous and gel phases following exposure of TIP to a broad range of relative humidity and temperature. Because changes in either particle morphology or the solid-state form of the drug could affect drug delivery or biopharmaceutical properties, understanding physical stability was critical to development and registration of this product. This characterization included morphological assessments of particles, thermal analysis to measure the gel-to-liquid crystalline phase transition (Tm) and the glass transition temperature (Tg), enthalpy relaxation measurements to determine structural relaxation times, and gravimetric vapor sorption to measure moisture sorption isotherms of TIP and its components. Collectively, these data enabled development of a state diagram for TIP, a map of the environmental conditions under which physical stability can be expected. This diagram shows that, under long-term storage conditions, TIP is at least 50°C below the Tg of the amorphous phase and at least 40°C below the Tm of the gel phase. Enthalpy relaxation measurements demonstrate that the characteristic structural relaxation times under these storage conditions are many orders of magnitude greater than that at Tg. These data, along with long-term physicochemical stability studies conducted during product development, demonstrate that TIP is physically stable, remaining as a mechanical solid over timescales and conditions relevant to a pharmaceutical product. This met a key design goal in the development of TIP: a room-temperature-stable formulation (three years at room temperature) that obviates the need for refrigeration for long-term storage. This has enabled development of TOBI® Podhaler™ - an approved inhaled drug product that meaningfully reduces the treatment burden of cystic fibrosis patients worldwide

On the measurement of microclimate

1. Many organisms live in environments in which temperatures differ substantially from those measured by standard weather stations. The last decade has witnessed a paradigm shift in efforts to quantify these differences and to understand their ecological, functional and evolutionary implications. This renewed interest in microclimate ecology has been accompanied by the development of various compact temperature sensors and radiation shields. However, it is clear that there are many pitfalls when measuring temperature using these devices. 2. Here we address the problem of measuring temperatures in these microenvironments accurately. We first discuss the theory of measuring surface, ground and air temperatures with reference to energy fluxes and how these are modified by material, reflective properties and size of the device. We highlight the particular difficulties associated with measuring air temperature. We then report on the results of a series of experiments in which air temperatures recorded by various commonly used microclimate temperature loggers are compared to those obtained using research-grade instruments and synoptic weather stations. 3. While accurate measurements of surface and ground temperatures and air temperatures at night and in shaded environments can be relatively easily obtained, we show substantial errors are to be expected when measuring air temperatures in environments exposed to sunlight. Most standard sensors yield large errors, which can reach 25 degrees C due to radiative fluxes operating on the thermometer. This problem cannot be wholly overcome by shielding the thermometer from sunlight, as the shield itself will influence both the temperatures being measured and the accuracy of measurement. 4. We demonstrate that reasonably accurate estimates of air temperature can be obtained with low-cost and unshielded ultrafine-wire thermocouples that possess low thermal emissivity and a highly reflective surface. As the processes that create microclimatic temperature variation are the same as those that cause errors, other logger types should be used with care, and generally avoided in environments exposed to sunlight and close to the ground where wind speeds are lower. We urge researchers interested in microclimates and their effects to pay greater heed to the physics of heat exchange when attempting to measure microclimate temperatures and to understand the trade-offs that exist in doing so