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MicroRNAs (miRNAs) represent endogenous small RNAs that post-transcriptionally regulate gene expression and, thus they are involved in the onset and progression of various diseases and conditions (Bader et al., 2010) such as for overweight and obesity. Antiadipogenic miRNA-27a is a negative regulator in fat metabolism, which inhibits adipocyte differentiation through downregulation of adipogenic marker genes (e.g. PPARγ) (Kim et al., 2010). Reduced miRNA-27a levels are often associated with the development of obesity and, therefore, this miRNA might represent a promising candidate for miRNA mimic replacement therapy (Lin et al., 2009). However, the application of naked RNAs has shown low membrane permeability, cellular uptake, and rapid degradation in the circulation. The present study aimed to develop a cationic, lipid-based nanoparticle system for targeting adipose tissue and delivering miRNA-27a. These systems are composed of positively charged nanostructured lipid carriers (cNLCs) and negatively charged miRNAs, which results in complex formation based on electrostatic interactions between these components. Materials and methods

Omeprazole is a proton pump inhibitor commonly used in pediatric patients (Wensel, 2009). Pediatric patients are usually unable to swallow solid dosage forms and they need dose adjustment. Therefore, the dosage form of choice for this population is compounded liquid preparation. Since pharmacies don't usually dispose of pure active substances, compounded liquid preparations are most commonly prepared from commercially available solid dosage forms, in a way that tablets are simply pulverized or capsule contents emptied, adding water or one of the commercially available vehicles (Haywood and Glass, 2013). Considering the risks associated with the preparation and use of compounded preparations, the Chapter <795> of the US Pharmacopoeia states that the beyond-use date is 14 days for non-preserved aqueous oral formulations, if stored in the refrigerator. Preserved aqueous preparations can be stored for 35 days at controlled room temperature or in the refrigerator (USP, 2015).

Many different and innovative approaches have been investigated to reduce the barrier effects of the stratum corneum (SC) and one of those are microneedles. Microneedles (MNs) are micron-sized needles which assist drug delivery through skin by creating microchannels (micron-scale pores) in SC that are large enough to enable drugs, including macromolecules, to enter the skin while being small enough to avoid pain, irritation and needle phobia. They have the capacity to play a role in modern healthcare as they reduce pain, tissue damage and transmission of infection and have potential for selfadministration in comparison to traditional needles. MNs have been fabricated by a variety of methods, from a range of materials (including silicon, glass, metal, carbohydrates and polymers) and in varying geometries (Quinn et al., 2014). Additive manufacturing (AM), more commonly known as three-dimensional (3D) printing represents a new, cutting-edge technology of 3D objects fabricated from a digital model generated using computer-aided design (CAD) software by fusing or depositing proper material (e.g., ceramics, liquids, metal, plastic, powders or even living cells) in layers. Suitable thermoplastic material in the form of a filament is fed into the printer by rollers, where it is heated to just above its softening point (glass transition temperature, Tg) by heating elements into a molten state. The melted or softened material guided by gears is moved towards heat end where it is extruded from the printer’s head, through a nozzle and subsequently deposited layer-by-layer on a build plate, cooling and solidifying in under a second. The printer’s head moves within the xand y-axes, whereas the platform can move within the z-axis, thus creating 3D structures (Alhnan et al., 2016; Goole and Amighi, 2016; Jamróz, 2018; Prased and Smyth, 2016). The aim of this work was to fabricate biodegradable PLA microneedles using innovative FDM 3D-printing technology on two different 3D printers and then chemically etch their arrays to obtain ideally sized and shaped needles.

Approximately 70-90% of the new active pharmaceutical ingredients/drugs are poorly soluble in water/biological fluids. Improvement of solubility, dissolution rate, bioavailability are the main characteristics of drug nanocrystals that are important for oral drug administration. High bioadhesive activity, depending on the type of stabilizer, is considered to be an essential feature of drug nanocrystals for oral, dermal, ocular dosage forms (Chang et al., 2015; Sheokand et al., 2018; Tuomela et al., 2016). Drug nanocrystals are solid nanosized particles of pharmacologically active substances, mainly BCS class IIa and IIb, 200 to 600 nm in diameter, homogeneously coated with 10-50% stabilizer/surfactants and/or polymers, forming ultrafine dispersion (Malamatari et al., 2018). Drug nanocrystals are usually in the crystalline state, but depending on the manufacturing method and process parameters, they may be in the amorphous state (Shete et al., 2014). Drug nanocrystals can be obtained by increasing their particle size by controlled precipitation/agglomeration from solution or by reducing drug particle size by milling to the desirable size. The two basic methods for obtaining drug nanocrystals are bottom up (e.g., precipitation) and top down (e.g., milling) methods, or drug nanocrystals can be made by a combination of these processes. By combining these two methods the desired particle size of drugs can be achieved and disadvantages of the individual methods are overcomed. These methods are intended for the preparation of liquid pharmaceutical nanosuspensions whose internal phase consists of drug nanocrystals particles, which can be converted into solid drug nanocrystals by post-production processes (spray drying, freeze drying or other process) in order to improve chemical, physical stability of drug during storage, when the selected stabilizer of drug nanocrystal could not provide long-term stability of the liquid nanosuspension (Sheokand et al., 2018).

M. Buckwell, W. H. Ng, D. Mannion, S. Hudziak, A. Mehonic, A. Kenyon

Resistive random-access memories, also known as memristors, whose resistance can be modulated by the electrically driven formation and disruption of conductive filaments within an insulator, are promising candidates for neuromorphic applications due to their scalability, low-power operation and diverse functional behaviours. However, understanding the dynamics of individual filaments, and the surrounding material, is challenging, owing to the typically very large cross-sectional areas of test devices relative to the nanometre scale of individual filaments. In the present work, conductive atomic force microscopy is used to study the evolution of conductivity at the nanoscale in a fully CMOS-compatible silicon suboxide thin film. Distinct filamentary plasticity and background conductivity enhancement are reported, suggesting that device behaviour might be best described by composite core (filament) and shell (background conductivity) dynamics. Furthermore, constant current measurements demonstrate an interplay between filament formation and rupture, resulting in current-controlled voltage spiking in nanoscale regions, with an estimated optimal energy consumption of 25 attojoules per spike. This is very promising for extremely low-power neuromorphic computation and suggests that the dynamic behaviour observed in larger devices should persist and improve as dimensions are scaled down.

C. Diouf, H. Dun, Tarik Kazaz, G. Janssen, C. Tiberius

Global Navigation Satellite Systems (GNSS) are nowadays the most common solutions used to cope with Positioning-Navigation-Timing (PNT) applications demands. GNSS are relied on in very diverse contexts and domains, yet the interest in systems such as GPS, GALILEO and Beidou is continuously increasing. However

I. Gupta, A. Jabeen, M. Smatti, Hamda A. Al-Thawadi, Gheyath K. Nasrallah, A. Sultan, M. Alkhalaf, S. Vranić et al.

Introduction: Infections with human oncoviruses such as high-risk human papillomaviruses (HPVs) and Epstein-Barr virus (EBV) are globally prevalent in the adult population. Both viruses are strongly associated with several types of human carcinomas such as cervical, head and neck, nasopharyngeal and gastric. In the present study, we explored the prevalence of these two oncoviruses in the healthy population of Qatar. Methods: The study included 385 healthy blood donors that reflect diverse nationalities in the Qatari community (Qatar, Egypt, Syria, Jordan, Pakistan, and India). DNA was extracted from the peripheral blood and genotyping was done using PCR and nested-PCR targeting E6 and E7 as well as LMP1 genes of HPVs and EBV, respectively. Results: The age of participants (378 males and 7 females) ranged between 19 and 68 years (mean 37.12 ± 9.3 years). Our data indicate that 55% and 61% of the tested samples were HPVs and EBV positive, respectively. Moreover, we found that there was (40%) co-presence of both HPVs and EBV in our samples. The most common high-risk HPV types in Qatar included HPV 59 (55%), 31 (54%), 52 (49%), 51 (49%), 58 (47%) and 35 (46%). While, HPV 16 and 18 were detected in 38% and 36% of the samples, respectively. Notably, all samples showed multiple HPVs infections. Conclusion: Our study reveals for the first time a high prevalence of both EBV and HPVs among healthy individuals in Qatar. More significantly, most cases had multiple HPV types infection in addition to the co-presence of both viruses in a substantial proportion of the samples. Given the important possible cooperative role of these viruses in human carcinogenesis, preventive measures using available and upcoming vaccines are of paramount importance.

Karim Nagi, I. Gupta, Hamda A. Al-Thawadi, A. Jabeen, Mohammed I. Malk, S. Vranić, A. Al-Moustafa

Background: Several studies have shown the presence of onco viral DNA in colorectal tumor tissues. Viral infection by onco-viruses such as Human papillomaviruses (HPVs) and Epstein–Barr virus (EBV) are well-known to be involved in the onset and/or progression of numerous human carcinomas. Methods: We explored the co-presence of high-risk HPVs and EBV in a cohort of colorectal cancer samples from Lebanon (94) and Syria (102) by PCR, immunohistochemistry and tissue microarray. Results: The results of the study point out that 54% of colorectal cancer cases in Syria are positive for high-risk HPVs, while 30% of the cases in Lebanon are positive for these viruses; the most frequent high-risk HPV types in these populations are 16, 18, 31, 33 and 35. Analysis of LMP1 showed similar results in both populations; 36% of Syrian and 31% of Lebanese samples. Additionally, we report that EBV and high-risk HPVs are co-present in these samples. In Syrian samples, EBV and HPVs are co-present in 16% of the population, however, in the Lebanese samples, 20% of the cases are positive for both EBV and HPVs; their co-presence is associated with high/intermediate grade invasive carcinomas. Conclusion: These data suggest that EBV and high-risk HPVs are co-present in human colorectal cancers where they can cooperate in the progression of these cancers. Nevertheless, further studies are needed to elucidate the role of those oncoviruses in the development of human colorectal carcinomas.

M. Kozieł, M. Mihajlovic, M. Nedeljkovic, N. Pavlović, V. Paparisto, L. Musić, E. Trendafilova, Anca Rodica Dan et al.

Symptom‐focused management is one of the cornerstones of optimal atrial fibrillation (AF) therapy.

Hyun-Chae Loh, T. Divoux, B. Gludovatz, P. Gilbert, R. Ritchie, F. Ulm, A. Masic

Nacre’s structure-property relationships have been a source of inspiration for designing advanced functional materials with both high strength and toughness. These outstanding mechanical properties have been mostly attributed to the interplay between aragonite platelets and organic matrices in the typical brick-and-mortar structure. Here, we show that crystallographically co-oriented stacks of aragonite platelets, in both columnar and sheet nacre, define another hierarchical level that contributes to the toughening of nacre. By correlating piezo-Raman and micro-indentation results, we quantify the residual strain energy associated with strain hardening capacity. Our findings suggest that the aragonite stacks, with characteristic dimensions of around 20 µm, effectively store energy through cooperative plastic deformation. The existence of a larger length scale beyond the brick-and-mortar structure offers an opportunity for a more efficient implementation of biomimetic design. The hierarchical structure of nacre is known to contribute to its high strength and toughness, providing inspiration for many biomimetic materials. Here, co-oriented 20 µm stacks of aragonite platelets are shown to contribute to the toughness of nacre, defining a new characteristic length scale.

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