Demographic buffering and compensatory recruitment promotes the persistence of disease in a wildlife population

Demographic buffering allows populations to persist by compensating for fluctuations in vital rates, including disease‐induced mortality. Using long‐term data on a badger (Meles meles Linnaeus, 1758) population naturally infected with Mycobacterium bovis, we built an integrated population model to quantify impacts of disease, density and environmental drivers on survival and recruitment. Badgers exhibit a slow life‐history strategy, having high rates of adult survival with low variance, and low but variable rates of recruitment. Recruitment exhibited strong negative density‐dependence, but was not influenced by disease, while adult survival was density independent but declined with increasing prevalence of diseased individuals. Given that reproductive success is not depressed by disease prevalence, density‐dependent recruitment of cubs is likely to compensate for disease‐induced mortality. This combination of slow life history and compensatory recruitment promotes the persistence of a naturally infected badger population and helps to explain the badger's role as a persistent reservoir of M. bovis.     

Fusion Method for Solubility and Dissolution Rate Enhancement of Ibuprofen Using Block Copolymer Poloxamer 407

Aim of current research was to prepare ibuprofen-poloxamer 407 binary mixtures using fusion method and characterize them for their physicochemical and performance properties. Binary mixtures of ibuprofen and poloxamer were prepared in three different ratios (1:0.25, 1:0.5, and 1:0.75, respectively) using a water-jacketed high shear mixer. In vitro dissolution and saturation solubility studies were carried out for the drug, physical mixtures, and formulations for all ratios in de-ionized water, 0.1 N HCl (pH?=?1.2), and phosphate buffer (pH?=?7.2). Thermal and physical characterization of samples was done using modulated differential scanning calorimetry (mDSC), X-ray powder diffraction (XRD), and infrared spectroscopy (FTIR). Flow properties were evaluated using a powder rheometer. Maximum solubility enhancement was seen in acidic media for fused formulations where the ratio 1:0.75 had 18-fold increase. In vitro dissolution studies showed dissolution rate enhancement for physical mixtures and the formulations in all three media. The most pronounced effect was seen for formulation (1:0.75) in acidic media where the cumulative drug release was 58.27% while for drug, it was 3.67%. Model independent statistical methods and ANOVA based methods were used to check the significance of difference in the dissolution profiles. Thermograms from mDSC showed a characteristic peak for all formulations with T_peak of around 45°C which suggested formation of a eutectic mixture. XRD data displayed that crystalline nature of ibuprofen was intact in the formulations. This work shows the effect of eutectic formation and micellar solubilization between ibuprofen and poloxamer at the given ratios on its solubility and dissolution rate enhancement.     

Thermal Processing of PVP- and HPMC-Based Amorphous Solid Dispersions

Thermal processing technologies continue to gain interest in pharmaceutical manufacturing. However, the types and grades of polymers that can be utilized in common thermal processing technologies, such as hot-melt extrusion (HME), are often limited by thermal or rheological factors. The objectives of the present study were to compare and contrast two thermal processing methods, HME and KinetiSol® Dispersing (KSD), and investigate the influence of polymer type, polymer molecular weight, and drug loading on the ability to produce amorphous solid dispersions (ASDs) containing the model compound griseofulvin (GRIS). Dispersions were analyzed by a variety of imaging, solid-state, thermal, and solution-state techniques. Dispersions were prepared by both HME and KSD using polyvinylpyrrolidone (PVP) K17 or hydroxypropyl methylcellulose (HPMC) E5. Dispersions were only prepared by KSD using higher molecular weight grades of HPMC and PVP, as these could not be extruded under the conditions selected. Powder X-ray diffraction (PXRD) analysis showed that dispersions prepared by HME were amorphous at 10% and 20% drug load; however, it showed significant crystallinity at 40% drug load. PXRD analysis of KSD samples showed all formulations and drug loads to be amorphous with the exception of trace crystallinity seen in PVP K17 and PVP K30 samples at 40% drug load. These results were further supported by other analytical techniques. KSD produced amorphous dispersions at higher drug loads than could be prepared by HME, as well as with higher molecular weight polymers that were not processable by HME, due to its higher rate of shear and torque output.     

T-cell therapies for T-cell lymphoma

T-cell lymphomas represent a subpopulation of non-Hodgkin lymphomas with poor outcomes when treated with conventional chemotherapy. A variety of novel agents have been introduced as new treatment strategies either as first-line treatment or in conjunction with chemotherapy. Immunotherapy has been demonstrated to be a promising area for new therapeutics, including monoclonal antibodies and adoptive cellular therapeutics. T-cell therapeutics have been shown to have significant success in the treatment of B-cell malignancies and are rapidly expanding as potential treatment options for other cancers including T-cell lymphomas. Although treating T-cell lymphomas with T-cell therapeutics has unique challenges, multiple targets are currently being studied both preclinically and in clinical trials.     

Big cats at large: Density,structure, and spatio-temporal patterns of a leopard population free of anthropogenic mortality

Human impact is near pervasive across the planet and studies of wildlife populations free of anthropogenic mortality are increasingly scarce. This is particularly true for large carnivores that often compete with and, in turn, are killed by humans. Accordingly, the densities at which carnivore populations occur naturally, and their role in shaping and/or being shaped by natural processes, are frequently unknown. We undertook a camera-trap survey in the Sabi Sand Game Reserve (SSGR), South Africa, to examine the density, structure and spatio-temporal patterns of a leopard Panthera pardus population largely unaffected by anthropogenic mortality. Estimated population density based on spatial capture–recapture models was 11.8 ± 2.6 leopards/100 km². This is likely close to the upper density limit attainable by leopards, and can be attributed to high levels of protection (particularly, an absence of detrimental edge effects) and optimal habitat (in terms of prey availability and cover for hunting) within the SSGR. Although our spatio-temporal analyses indicated that leopard space use was modulated primarily by “bottom-up” forces, the population appeared to be self-regulating and at a threshold that is unlikely to change, irrespective of increases in prey abundance. Our study provides unique insight into a naturally-functioning carnivore population at its ecological carrying capacity. Such insight can potentially be used to assess the health of other leopard populations, inform conservation targets, and anticipate the outcomes of population recovery attempts.     

TLR- and NOD2-dependent regulation of human phagocyte-specific chitotriosidase

Human chitotriosidase is specifically expressed by phagocytes, has anti-fungal activity towards chitin-containing fungi in vitro and in vivo, and is part of innate immunity. We studied the effect of toll-like receptor (TLR)- and nucleotide-binding oligomerization domain (NOD)-2 triggering on chitotriosidase expression and release by phagocytes. We find that TLR, but not NOD2 activation, regulates chitotriosidase release by neutrophils. Furthermore, both TLR and NOD2 activation resulted in diminished induction by monocytes. Lastly, NOD2 activation, but not TLR stimulation, induces chitinase expression in macrophages. We conclude that phagocyte-specific regulation is important for efficient eradication of chitin-containing pathogens.