Alginate Microsphere Encapsulation of Drug-Loaded Nanoparticles: A Novel Strategy for Intraperitoneal Drug Delivery

Alginate hydrogels have been broadly investigated for use in medical applications due to their biocompatibility and the possibility to encapsulate cells, proteins, and drugs. In the treatment of peritoneal metastasis, rapid drug clearance from the peritoneal cavity is a major challenge. Aiming to delay drug absorption and reduce toxic side effects, cabazitaxel (CAB)-loaded poly(alkyl cyanoacrylate) (PACA) nanoparticles were encapsulated in alginate microspheres. The PACAlg alginate microspheres were synthesized by electrostatic droplet generation and the physicochemical properties, stability, drug release kinetics, and mesothelial cytotoxicity were analyzed before biodistribution and therapeutic efficacy were studied in mice. The 450 µm microspheres were stable at in vivo conditions for at least 21 days after intraperitoneal implantation in mice, and distributed evenly throughout the peritoneal cavity without aggregation or adhesion. The nanoparticles were stably retained in the alginate microspheres, and nanoparticle toxicity to mesothelial cells was reduced, while the therapeutic efficacy of free CAB was maintained or improved in vivo. Altogether, this work presents the alginate encapsulation of drug-loaded nanoparticles as a promising novel strategy for the treatment of peritoneal metastasis that can improve the therapeutic ratio between toxicity and therapeutic efficacy.     

Effect of air exposure on scallop behaviour, and the implications for subsequent survival in culture

Scallop spat produced for continued culture normally requiretransportation between sites, and the associated stresses may causemortalities. In the present experiment, scallops of 40–55 mm shell heightwere emersed in air for time intervals up to 24 h and their behaviourexamined once re-immersed. Scallops were placed upside-down and thenumber of movements and the cumulative numbers righting in 5 min timeblocks were recorded. The greatest frequency for all behaviouralresponses was found at 15–17 °C in August. Responses were reducedin November and June (9–11 °C) and least at 5 °C in January.All effects of treatment, temperatures and season, and increases in airexposure were significantly different. Following the treatments, mortalitiesafter 10 days in culture was about 10–30% for scallops emersed for 18 and24 h in August and June. Scallops did not show significantly differentbehaviour whether they were emersed upright or inverted. However,scallops emersed at 15 °C had fewer responses than scallops held at <10 °C, so chilling during transport may prolong scallop vitality. Theresults suggest that air exposure >12 h should be avoided. At temperatures>9 °C, behavioural responses may be a simple and effective method toassess vitality which can assist in the management of scallop culture.     

Single step genomic evaluation for female fertility in Nordic Red dairy cattle

Joint Nordic (Denmark, Finland, Sweden) genetic evaluation of female fertility is currently based on the multiple trait multilactation animal model (BLUP). Here, single step genomic model (ssGBLUP) was applied for the Nordic Red dairy cattle fertility evaluation. The 11 traits comprised of nonreturn rate and days from first to last insemination in heifers and first three parities, and days from calving to first insemination in the first three parities. Traits had low heritabilities (0.015–0.04), but moderately high genetic correlations between the parities (0.60–0.88). Phenotypic data included 4,226,715 animals with records and pedigree 5,445,392 animals. Unknown parents were assigned into 332 phantom parent groups (PPG). In mixed model equations animals were associated with PPG effects through the pedigree or both the pedigree and genomic information. Genotype information of 46,914 SNPs was available for 33,969 animals in the pedigree. When PPG used pedigree information only, BLUP converged after 2,420 iterations whereas the ssGBLUP evaluation needed over ten thousand iterations. When the PPG effects were solved accounting both the pedigree and the genomic information, the ssGBLUP model converged after 2,406 iterations. Also, with the latter model breeding values by ssGBLUP and BLUP became more consistent and genetic trends followed each other well. Models were validated using forward prediction of the young bulls. Reliabilities and variance inflation of predicted genomic breeding values (values for parent averages in brackets) for the 11 traits ranged 0.22–0.31 (0.10–0.27) and 0.81–0.95 (0.83–1.06), respectively. The ssGBLUP model gave always higher validation reliabilities than BLUP, but largest increases were for the cow fertility traits.     

Impact of Honey Bee Migratory Management on Pathogen Loads and Immune Gene Expression is Affected by Complex Interactions With Environment,Worker Life History,and Season

The effects of honey bee management, such as intensive migratory beekeeping, are part of the ongoing debate concerning causes of colony health problems. Even though comparisons of disease and pathogen loads among differently managed colonies indicate some effects, the direct impact of migratory practices on honey bee pathogens is poorly understood. To test long- and short-term impacts of managed migration on pathogen loads and immunity, experimental honey bee colonies were maintained with or without migratory movement. Individuals that experienced migration as juveniles (e.g., larval and pupal development), as adults, or both were compared to control colonies that remained stationary and therefore did not experience migratory relocation. Samples at different ages and life-history stages (hive bees or foragers), taken at the beginning and end of the active season, were analyzed for pathogen loads and physiological markers of health. Bees exposed to migratory management during adulthood had increased levels of the AKI virus complex (Acute bee paralysis, Kashmir bee, and Israeli acute bee paralysis viruses) and decreased levels of antiviral gene expression (dicer-like). However, those in stationary management as adults had elevated gut parasites (i.e. trypanosomes). Effects of environment during juvenile development were more complex and interacted with life-history stage and season. Age at collection, life-history stage, and season all influenced numerous factors from viral load to immune gene expression. Although the factors that we examined are not independent, the results illuminate potential factors in both migratory and nonmigratory beekeeping that are likely to contribute to colony stress, and also indicate potential mitigation measures.     

A Rapid Method for the Determination of Radioactive Caesium in Live Animals and Carcasses,and its Practical Application in Norway after the Chernobyl Nuclear Reactor Accident

A technique was developed for the measurement of levels of caesium radionuclides (¹³⁷Cs+¹³⁴Cs) in live reindeer, cattle, and sheep and in carcasses from these species. The instrument used was a sodium iodide scintillation detector coupled to a portable multi-channel analyser.Based on a combination of background measurements and measurements of impulses from animals with the detector in different anatomical positions we recommmend the following procedures: Lamb: The detector placed on os sacrum (standing animal). Reindeer: The detector placed between the hind legs (animal lying on its side). Cattle: The detector placed on the back of the standing animal, midway between os sacrum and trochanter major.Average geometrical factors for live animals were estimated. It was a linear correlation between measured activity levels in meat samples and counted impulses per sec in live animals. Geometrical factors were estimated at 95% confidence level with uncertainty between 6–14%. The detection limits varied between 50–200 Bq (becquerel)/kg in areas with ground depositions between 5–200 kBq/m². Since the winter 1986/87 the technique has been the standard procedure for monitoring slaughter animals and carcasses for radiocaesium activity concentrations.     

Employing a Monte Carlo algorithm in expectation maximization restricted maximum likelihood estimation of the linear mixed model

Multiple‐trait and random regression models have multiplied the number of equations needed for the estimation of variance components. To avoid inversion or decomposition of a large coefficient matrix, we propose estimation of variance components by Monte Carlo expectation maximization restricted maximum likelihood (MC EM REML) for multiple‐trait linear mixed models. Implementation is based on full‐model sampling for calculating the prediction error variances required for EM REML. Performance of the analytical and the MC EM REML algorithm was compared using a simulated and a field data set. For field data, results from both algorithms corresponded well even with one MC sample within an MC EM REML round. The magnitude of the standard errors of estimated prediction error variances depended on the formula used to calculate them and on the MC sample size within an MC EM REML round. Sampling variation in MC EM REML did not impair the convergence behaviour of the solutions compared with analytical EM REML analysis. A convergence criterion that takes into account the sampling variation was developed to monitor convergence for the MC EM REML algorithm. For the field data set, MC EM REML proved far superior to analytical EM REML both in computing time and in memory need.     

Forecasting the Genetic Impacts of Net Pen Failures on Gulf of Mexico Cobia Populations Using Individual‐based Model Simulations

Offshore net pen fish farming provides a cost‐efficient means for production of marine finfish, and there is great interest in development of net pen operations in domestic waters. However, there are concerns over the possible genetic and ecological impacts that escaped fish may have on wild populations. We used individual‐based simulations, with parameter values informed by life history and genetic data, to investigate the short‐term (50 yr) impacts of net pen failures on the genetic composition of cobia, Rachycentron canadum, stocks in the Gulf of Mexico. Higher net pen failure rates resulted in greater genetic impacts on the wild population. Additionally, the use of more genetically differentiated source populations led to larger influxes of non‐native alleles and greater temporal genetic change in the population as a result of net pen failure. Our results highlight the importance of considering the appropriate source population for broodstock collection in net pen aquaculture systems and help to provide a general set of best management practices for broodstock selection and maintenance in net pen aquaculture operations. A thorough understanding of the genetic diversity, stock structure, and population demography of target species is important to determine the impact escapees can have on wild populations.     

Effects of low night temperature and light on chlorophyll fluorescence of field-grown seedlings of Scots pine (Pinus sylvestris L.)

In vivo chlorophyll fluorescence kinetics was observed in naturally regenerated and planted Scots pine (Pinus sylvestris L.) seedlings growing at two adjacent sites in northern Sweden. Some seedlings were shaded from direct solar radiation and some were protected from frost at night. Air temperature and solar radiation were monitored. In vivo chlorophyll fluorescence kinetics of current-year needles was measured at both room temperature and 77 K. On clear days during August, variable fluorescence of photosystem II of needles from exposed, naturally regenerated seedlings was reduced by night frosts, whereas frost caused little change in fluorescence of needles from shaded seedlings. Overnight frost-protection reduced the inhibition of photosystem II by direct sunlight. Recovery from photoinhibitory damage occurred on cloudy days. In September, the decline of variable fluorescence of photosystem II was more pronounced in unshaded than in shaded seedlings, and coincided with frosts at night. In addition, the reduction in variable fluorescence was larger for planted seedlings than for naturally regenerated seedlings. It is suggested that the inhibition of photosystem II activity was caused by an interaction between low temperatures and light. Natural night frosts are proposed to increase the susceptibility to photoinhibition in the following day(s).