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Here we describe a rapid inkjet formulation method for screening newly-synthesised cationic materials for siRNA delivery into cancer cells. Reduction responsive oligo-β-aminoesters were prepared and evaluated for their ability to condense siRNA into polyplexes through a fast inkjet printing method. A direct relationship between the oligomer structures and charge densities, and the final cell response in terms of uptake rate and transfection efficacy, was found. The oligo-β-aminoesters were well-tolerated by the cancer cells, compared to conventional cationic polymers so far employed in gene delivery, and were as active in silencing of a representative luciferase gene. [ABSTRACT FROM AUTHOR]

The European honeybee, Apis mellifera L. (Hymenoptera: Apidae), is considered as a main contributor to pollination of important crops and to honey production. Originally, beekeeping in Argentina was performed in an extended area covering the north and central region of the country and involving A. mellifera of European origin. Later, honeybees of African origin entered South America through Brazil and hybridized with European genetic resources, giving rise to Africanized populations that are characterized by a more aggressive behavior among other unfavorable traits. In this study, a genetic characterization of 396 honeybee colonies from the most important apicultural region of Argentina is presented in order to provide an updated description of population structure and genetic diversity of commercial and feral colonies. Diversity was analyzed using mitochondrial (COI‐COII region) and nuclear (eight microsatellites) markers. Three European (M4, C1, C2J) and three African (A1, A4, A30) haplotypes were detected. European haplotypes were mostly found in commercial apiaries, whereas African haplotypes were detected at high frequencies in feral colonies. Microsatellite data were analyzed to estimate population genetic variability at the province level and to evaluate genetic admixture. A high level of hybridization between Africanized and European honeybees was detected with a significant latitudinal cline from north to south. Extensive population admixture resulted in the definition of four clusters that included both feral and commercial colonies and that are explained not only by geographical distribution and degree of Africanization but also by human influence through beekeeping activities. Genetic characterization of 396 Argentinean honeybee colonies provides an updated description of population structure and diversity of commercial and feral colonies. European haplotypes were mostly found in commercial apiaries, whereas African haplotypes were often detected in feral colonies. Microsatellite data indicated a high level of hybridization between Africanized and European honeybees with a cline from north to south. Extensive population admixture resulted in the definition of four clusters, explained by geographical distribution, degree of Africanization, and human influence through apiculturing. [ABSTRACT FROM AUTHOR]

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Diachasmimorpha longicaudatais a koinobiont larval parasitoid that is currently used to control fruit flies of the generaAnastrepha,CeratitisandBactrocera.In the rearing process, a fraction of the host larvae that are exposed to parasitoids escape from parasitism and develop into viable and fertile flies. This creates the need to eliminate emerging flies before the parasitoids are shipped for release, increasing costs due to additional handling steps. Exposure of fly eggs or larvae to gamma-irradiation before they are parasitised has been used to reproductively sterilise hosts, or even inhibit their emergence. Our aim was to determine whether X-ray radiation applied toAnastrepha fraterculusthird instar larvae before they are exposed to parasitoids, inhibits fly emergence in non-parasitised larvae without affecting the performance of the parasitoids that emerge from parasitised larvae. Three X-ray doses: 6250.2 R, 8333.6 R and 10417 R (equivalent to 60, 80 and 100 Gy, respectively) and oneγ-ray dose (100 Gy) were tested. Fly emergence decreased with increasing doses of radiation, showing null values for the higher X-ray dose and the dose of 100 Gy. Irradiation showed either no impact or a positive effect on parasitism rate and fecundity. Sex rate was biased towards females in almost every dose. We conclude that the two types of radiation evaluated here were equally effective in suppressing fly emergence with no detrimental effects on the biological quality of the produced parasitoids. X-rays offer an alternative method of irradiation than the conventional radiation source, i.e.γ-rays. These results represent a significant improvement in the development of a biological control programme againstA. fraterculus. [ABSTRACT FROM AUTHOR]

Cystic fibrosis (CF) is the most common autosomal recessive disease in Caucasians associated with early death. Although the faulty gene is expressed in epithelia throughout the body, lung disease is still responsible for most of the morbidity and mortality of CF patients. As a local delivery route, pulmonary administration represents an ideal way to treat respiratory infections, excessive inflammation and other manifestations typical of CF lung disease. Nonetheless, important determinants of the clinical outcomes of inhaled drugs are the concentration/permanence at the lungs as well as the ability of the drug to overcome local extracellular and cellular barriers. This review focuses on emerging delivery strategies used for local treatment of CF pulmonary disease. After a brief description of the disease and formulation rules dictated by CF lung barriers, it describes current and future trends in inhaled drugs for CF. The most promising advanced formulations are discussed, highlighting the advantages along with the major challenges for researchers working in this field. [ABSTRACT FROM AUTHOR]

We evaluated the effects of X-ray irradiation on larvae ofCeratitis capitata(Wiedemann) (Diptera: Tephritidae), with the aim of finding a treatment that prevented adult fly emergence, yet did not adversely affect larval quality as rearing hosts for the parasitoidDiachasmimorpha longicaudata(Ashmead) (Hymenoptera: Ichneumonidae). Two experiments were carried out. In the first experiment, small numbers of larvae were held in Petri dishes with and without small amounts of rearing media and then irradiated with doses of X-rays ranging from 0 to 8333.6 R (equivalent to 80 Gy). In the second experiment, higher numbers of larvae were held in a manner resembling mass-rearing conditions, and were then irradiated with X-rays ranging from 0 to 10,417 R (equivalent to 100 Gy). In both experiments, the only factor that significantly affected fly emergence was irradiation of larvae. Fly emergence decreased markedly as the irradiation dose increased, and complete suppression of fly emergence was achieved at 6250.2 R (equivalent to 60 Gy) when larvae were irradiated in small batches with or without rearing media. Irradiation also affected the fertility of those flies that did emerge following treatment. In the second experiment, we found the parasitoids reared from irradiated larvae produced a higher parasitism rate and a higher number of female offspring than did parasitoids reared from control (non-irradiated) larvae. Mean fecundity of F1 parasitoids reared from irradiated larvae were affected positively by irradiation only at the 8333.6 R (80 Gy) dose. Our results show that X-ray irradiation can be used to inhibit fruit fly adult emergence and that irradiated larvae are at least as good a rearing substrate as non-irradiated larvae. Future studies should focus on the adjustment of our findings to a mass-rearing scale. [ABSTRACT FROM AUTHOR]

In recent years, the overall performances of inertial Micro-Electro Mechanical Sensors (MEMSs) exhibited substantial improvements to values very close or similar to so-called tactical-grade sensors. However, due to their high costs, numerous researchers are currently focusing on the performance enhancement of cheap consumer-grade MEMS inertial sensors for all those applications (as an example, small unmanned aerial vehicles, UAVs), where cost effectiveness is a relevant request; the use of redundancy proves to be a feasible method for this purpose. In this regard, the authors propose, hereinafter, a suitable strategy aimed at fusing raw measurements provided by multiple inertial sensors mounted on a 3D-printed structure. In particular, accelerations and angular rates measured by the sensors are averaged according to weights associated with the results of an Allan variance approach; the lower the noise figure of the sensors, the greater their weight on the final averaged values. On the other hand, possible effects on the measurements due to the use of a 3D structure in reinforced ONYX (a material capable of providing better mechanical specifications for avionic applications with respect to other solutions for additive manufacturing) were evaluated. The performance of a prototype implementing the considered strategy is compared with that of a tactical-grade inertial measurement unit in stationary conditions, exhibiting differences as low as 0.3 degrees in heading measurements. Moreover, the reinforced ONYX structure does not significantly affect the measured values in terms of both thermal and magnetic field while assuring better mechanical characteristics with respect to other 3D printing materials, thanks to a tensile strength of about 250 MPa and a specific stacking sequence of continuous fibers. Finally, a test conducted on an actual UAV highlights performance very close to that of a reference unit, with root-mean-square error in heading measurements as low as 0.3 degrees in observation intervals up to 140 s. [ABSTRACT FROM AUTHOR]

In this study, the structural attributes of nanoparticles obtained by a renewable and non-immunogenic "inulinated" analog of the "pegylated" PLA (PEG-PLA) were examined, together with the potential of these novel nanocarriers in delivering poorly water-soluble drugs. Characterization of INU-PLA assemblies, encompassing critical aggregation concentration (CAC), NMR, DLS, LDE, and SEM analyses, was conducted to elucidate the core/shell architecture of the carriers and in vitro cyto- and hemo-compatibility were assayed. The entrapment and in vitro delivery of sorafenib tosylate (ST) were also studied. INU-PLA copolymers exhibit distinctive features: (1) Crew-cut aggregates are formed with coronas of 2–4 nm; (2) a threshold surface density of 1 INU/nm2 triggers a configuration change; (3) INU surface density influences PLA core dynamics, with hydrophilic segment stretching affecting PLA distribution towards the interface. INU-PLA2NPs demonstrated an outstanding loading of ST and excellent biological profile, with effective internalization and ST delivery to HepG2 cells, yielding a comparable IC50. [ABSTRACT FROM AUTHOR]

The authors ascertained cardiovascular events (myocardial infarction and angina pectoris) in 498 women with systemic lupus erythematosus seen at the University of Pittsburgh Medical Center from 1980 to 1993 (3, 522 person-years). Subjects were stratified by age, and cardiovascular event incidence rates were determined. The authors compared these rates with cardiovascular event rates occurring over the same time period in 2, 208 women of similar age participating in the Framingham Offspring Study (17, 519 person-years). Age-specific rate ratios were computed to determine whether the cardiovascular events in the lupus cohort were greater than expected. The risk factors associated with cardiovascular events in women with lupus were determined. There were 33 first events (11 myocardial infarction, 10 angina pectoris, and 12 both angina pectoris and myocardial infarction) after the diagnosis of lupus; two thirds were under the age of 55 years at the time of event. Women with lupus in the 35- to 44-year age group were over 50 times more likely to have a myocardial infarction than were women of similar age in the Framingham Offspring Study (rate ratio = 52.43, 95% confidence interval 21.6–98.5). Older age at lupus diagnosis, longer lupus disease duration, longer duration of corticosteroid use, hypercholesterolemia, and postmenopausal status were more common in the women with lupus who had a cardiovascular event than in those who did not have an event. Premature cardiovascular disease is much more common in young premenopausal women with lupus than in a population sample. With the increased life expectancy of lupus patients due to improved therapy, cardiovascular disease has emerged as a significant threat to the health of these women. The impact of this problem has been underrecognized, with little focus placed on aggressive management of hypercholesterolemia and other possible risk factors. Am J Epidemiol 1997; 145: 408-15. [ABSTRACT FROM AUTHOR]

• Positively-charged zein nanoparticles are developed as mucoadhesive delivery platform for curcumin. • Cyclodextrin integration inside nanoparticles increases zeta potential and slows down curcumin release rate. • Nanoparticles demonstrate satisfactory colloidal stability and strongly interact with mucin. • A multi-dose spray pump allows the delivery of the nanoparticles and their secure anchoring to porcine buccal mucosa. • Prolonged residence time on the oral mucosa is envisaged to improve the effect of locally-acting drugs. Herein, we have developed sprayable dispersions of mucoadhesive nanoparticles (NPs) made of zein, a hydrophobic plant-based protein, for the buccal delivery of curcumin (CUR), a poorly water-soluble polyphenol. NPs were prepared by the liquid-liquid dispersion method using an antisolvent water solution without or with beta-cyclodextrin (CD). NPs were spherical with a monomodal size distribution, a mean size around 140 nm and low polydispersity. Excellent colloidal stability of NPs was found at room temperature for up to 1 month. CUR entrapment was found to depend mainly on the zein/CUR ratio and related to the ability of CUR to set within hydrophobic pockets in the zein matrix. CD addition generated an increase of NP zeta potential up to +60 mV, indicating that positively charged amino acids are prompted to settle on the NP surface. Fluorescence emission spectroscopy indicated that CD interacted with lipophilic amino acids of zein altering interchain interactions and formation of glutamine bridge. Because of zein/CD interactions, mainly occurring at NP periphery, the slowing down of the CUR release rate was observed too. A combination of spectroscopic techniques unequivocally showed that zein NPs strongly interacted with mucin due to electrostatic interactions. Once sprayed on a porcine buccal mucosa, zein/CD NPs securely attached to the tissue resisting repeated washing steps but did not allow CUR transmucosal permeation. Overall, these results point at zein/CD NPs as a novel mucoadhesive platform for the buccal delivery of poorly water-soluble molecules to use as both a food supplement or a drug product to achieve local effects. [ABSTRACT FROM AUTHOR]